Bio

Clinical Focus


  • Cancer > Urologic Oncology
  • Cancer > Cutaneous (Dermatologic) Oncology
  • Therapeutic Radiology
  • Radiation Therapy
  • Prostate Cancer
  • CNS Cancers
  • Lymphomas
  • Radiation Injuries
  • Cancer > Radiation Oncology

Academic Appointments


Professional Education


  • Residency:Stanford University School of Medicine (1981) CA
  • Residency:Stanford University School of Medicine (1980) CA
  • Residency:Stanford University School of Medicine (1978) CA
  • Internship:Stanford University School of Medicine (1977) CA
  • Board Certification: Therapeutic Radiology, American Board of Radiology (1982)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1980)
  • Medical Education:Stanford University School of Medicine (1976) CA

Research & Scholarship

Current Research and Scholarly Interests


Outcomes of radiation treatment for prostate cancer. Clinical research interests in the late effects of radiation on normal tissues and chemical modification of radiation injury.
Hodgkins's disease and late effects of radiation and combined modality therapy.
Radiation sensitizers and protectors.
Hypoxic cell cytotoxins.
Esophageal cancers.
General adult and pediatric radiation therapy.

Clinical Trials


  • Hypofractionated Radiotherapy for Localized Prostate Cancer (With CyberKnife or With IMRT) Not Recruiting

    To demonstrate that a hypo-fractionated course of radiotherapy (ie. an accelerated radiotherapy course where fewer but larger doses of radiotherapy are given) is both safe and effective in the treatment of low-risk localized prostate cancer.

    Stanford is currently not accepting patients for this trial. For more information, please contact Gillian McFarlane, (650) 721 - 2034.

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  • Radium-223 Dichloride (BAY88-8223) in Castration-Resistant (Hormone-Refractory) Prostate Cancer Patients With Bone Metastases Recruiting

    This study is a prospective, interventional, open-label, multi-center early access program for the use of Ra-223 Cl2 in HRPC/CRPC patients diagnosed with symptomatic bone metastasis and to collect additional short and long term safety data on the product.

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  • Real-Time MV/kV Image Guided Radiation Therapy Not Recruiting

    In current radiation therapy, imaging (typically, cone beam CT imaging or two orthogonal X-ray projection imaging) is done for patient setup before radiation dose delivery. Dose delivery typically takes 2 to 5 minutes depending on the delivery technique used for treatment. A tumor target may change its position during the dose delivery process. The goal of this project is develop a real-time imaging strategy to monitor the tumor position during dose delivery and evaluate its potential clinical impact.

    Stanford is currently not accepting patients for this trial. For more information, please contact Lei Xing, 650-498-7896.

    View full details

Teaching

2013-14 Courses


Publications

Journal Articles


  • Automatic prostate tracking and motion assessment in volumetric modulated arc therapy with an electronic portal imaging device. International journal of radiation oncology, biology, physics Azcona, J. D., Li, R., Mok, E., Hancock, S., Xing, L. 2013; 86 (4): 762-768

    Abstract

    PURPOSE: To assess the prostate intrafraction motion in volumetric modulated arc therapy treatments using cine megavoltage (MV) images acquired with an electronic portal imaging device (EPID). METHODS AND MATERIALS: Ten prostate cancer patients were treated with volumetric modulated arc therapy using a Varian TrueBeam linear accelerator equipped with an EPID for acquiring cine MV images during treatment. Cine MV images acquisition was scheduled for single or multiple treatment fractions (between 1 and 8). A novel automatic fiducial detection algorithm that can handle irregular multileaf collimator apertures, field edges, fast leaf and gantry movement, and MV image noise and artifacts in patient anatomy was used. All sets of images (approximately 25,000 images in total) were analyzed to measure the positioning accuracy of implanted fiducial markers and assess the prostate movement. RESULTS: Prostate motion can vary greatly in magnitude among different patients. Different motion patterns were identified, showing its unpredictability. The mean displacement and standard deviation of the intrafraction motion was generally less than 2.0 ± 2.0 mm in each of the spatial directions. In certain patients, however, the percentage of the treatment time in which the prostate is displaced more than 5 mm from its planned position in at least 1 spatial direction was 10% or more. The maximum prostate displacement observed was 13.3 mm. CONCLUSION: Prostate tracking and motion assessment was performed with MV imaging and an EPID. The amount of prostate motion observed suggests that patients will benefit from its real-time monitoring. Megavoltage imaging can provide the basis for real-time prostate tracking using conventional linear accelerators.

    View details for DOI 10.1016/j.ijrobp.2013.03.007

    View details for PubMedID 23608236

  • Development and clinical evaluation of automatic fiducial detection for tumor tracking in cine megavoltage images during volumetric modulated arc therapy MEDICAL PHYSICS Azcona, J. D., Li, R., Mok, E., Hancock, S., Xing, L. 2013; 40 (3)

    Abstract

    Real-time tracking of implanted fiducials in cine megavoltage (MV) imaging during volumetric modulated arc therapy (VMAT) delivery is complicated due to the inherent low contrast of MV images and potential blockage of dynamic leaves configurations. The purpose of this work is to develop a clinically practical autodetection algorithm for motion management during VMAT.The expected field-specific segments and the planned fiducial position from the Eclipse (Varian Medical Systems, Palo Alto, CA) treatment planning system were projected onto the MV images. The fiducials were enhanced by applying a Laplacian of Gaussian filter in the spatial domain for each image, with a blob-shaped object as the impulse response. The search of implanted fiducials was then performed on a region of interest centered on the projection of the fiducial when it was within an open field including the case when it was close to the field edge or partially occluded by the leaves. A universal template formula was proposed for template matching and normalized cross correlation was employed for its simplicity and computational efficiency. The search region for every image was adaptively updated through a prediction model that employed the 3D position of the fiducial estimated from the localized positions in previous images. This prediction model allowed the actual fiducial position to be tracked dynamically and was used to initialize the search region. The artifacts caused by electronic interference during the acquisition were effectively removed. A score map was computed by combining both morphological information and image intensity. The pixel location with the highest score was selected as the detected fiducial position. The sets of cine MV images taken during treatment were analyzed with in-house developed software written in MATLAB (The Mathworks, Inc., Natick, MA). Five prostate patients were analyzed to assess the algorithm performance by measuring their positioning accuracy during treatment.The algorithm was able to accurately localize the fiducial position on MV images with success rates of more than 90% per case. The percentage of images in which each fiducial was localized in the studied cases varied between 23% and 65%, with at least one fiducial having been localized between 40% and 95% of the images. This depended mainly on the modulation of the plan and fiducial blockage. The prostate movement in the presented cases varied between 0.8 and 3.5 mm (mean values). The maximum displacement detected among all patients was of 5.7 mm.An algorithm for automatic detection of fiducial markers in cine MV images has been developed and tested with five clinical cases. Despite the challenges posed by complex beam aperture shapes, fiducial localization close to the field edge, partial occlusion of fiducials, fast leaf and gantry movement, and inherently low MV image quality, good localization results were achieved in patient images. This work provides a technique for enabling real-time accurate fiducial detection and tumor tracking during VMAT treatments without the use of extra imaging dose.

    View details for DOI 10.1118/1.4791646

    View details for Web of Science ID 000316369400011

    View details for PubMedID 23464303

  • Esophageal tolerance to high-dose stereotactic ablative radiotherapy DISEASES OF THE ESOPHAGUS Abelson, J. A., Murphy, J. D., Loo, B. W., Chang, D. T., Daly, M. E., Wiegner, E. A., Hancock, S., Chang, S. D., Le, Q., Soltys, S. G., Gibbs, I. C. 2012; 25 (7): 623-629

    Abstract

    Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

    View details for DOI 10.1111/j.1442-2050.2011.01295.x

    View details for Web of Science ID 000308712300008

    View details for PubMedID 22168251

  • Testicular Cancer Clinical Practice Guidelines in Oncology JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK Motzer, R. J., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Buyyounouski, M. K., Carducci, M. A., Chang, S. S., Choueiri, T. K., Gupta, S., Hancock, S. L., Hudes, G. R., Jonasch, E., Kuzel, T. M., Lau, C., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Ratliff, T. W., Redman, B. G., Robertson, C. N., Ryan, C. J., Sheinfeld, J., Wang, J., Wilder, R. B. 2012; 10 (4): 502-535

    View details for Web of Science ID 000302445400009

    View details for PubMedID 22491049

  • Kidney cancer. Journal of the National Comprehensive Cancer Network Motzer, R. J., Agarwal, N., Beard, C., Bhayani, S., Bolger, G. B., Carducci, M. A., Chang, S. S., Choueiri, T. K., Hancock, S. L., Hudes, G. R., Jonasch, E., Josephson, D., Kuzel, T. M., Levine, E. G., Lin, D. W., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Ratliff, T. W., Redman, B. G., Robertson, C. N., Ryan, C. J., Sheinfeld, J., Spiess, P. E., Wang, J., Wilder, R. B. 2011; 9 (9): 960-977

    View details for PubMedID 21917622

  • Clinical development of a failure detection-based online repositioning strategy for prostate IMRT-Experiments, simulation, and dosimetry study MEDICAL PHYSICS Liu, W., Qian, J., Hancock, S. L., Xing, L., Luxton, G. 2010; 37 (10): 5287-5297

    Abstract

    To implement and evaluate clinic-ready adaptive imaging protocols for online patient repositioning (motion tracking) during prostate IMRT using treatment beam imaging supplemented by minimal, as-needed use of on-board kV.The authors examine the two-step decision-making strategy: (1) Use cine-MV imaging and online-updated characterization of prostate motion to detect target motion that is potentially beyond a predefined threshold and (2) use paired MV-kV 3D localization to determine overthreshold displacement and, if needed, reposition the patient. Two levels of clinical implementation were evaluated: (1) Field-by-field based motion correction for present-day linacs and (2) instantaneous repositioning for new-generation linacs with capabilities of simultaneous MV-kV imaging and remote automatic couch control during treatment delivery. Experiments were performed on a Varian Trilogy linac in clinical mode using a 4D motion phantom programed with prostate motion trajectories taken from patient data. Dosimetric impact was examined using a 2D ion chamber array. Simulations were done for 536 trajectories from 17 patients.Despite the loss of marker detection efficiency caused by the MLC leaves sometimes obscuring the field at the marker's projected position on the MV imager, the field-by-field correction halved (from 23% to 10%) the mean percentage of time that target displacement exceeded a 3 mm threshold, as compared to no intervention. This was achieved at minimal cost in additional imaging (average of one MV-kV pair per two to three treatment fractions) and with a very small number of repositionings (once every four to five fractions). Also with low kV usage (approximation 2/fraction), the instantaneous repositioning approach reduced overthreshold time by more than 75% (23% to 5%) even with severe MLC blockage as often encountered in current IMRT and could reduce the overthreshold time tenfold (to < 2%) if the MLC blockage problem were relieved. The information acquired for repositioning using combined MV-kV images was found to have submillimeter accuracy.This work demonstrated with a current clinical setup that substantial reduction of adverse targeting effects of intrafraction prostate motion can be realized. The proposed adaptive imaging strategy incurs minimal imaging dose to the patient as compared to other stereoscopic imaging techniques.

    View details for DOI 10.1118/1.3488887

    View details for Web of Science ID 000283483700016

    View details for PubMedID 21089763

  • NCCN clinical practice guidelines in oncology: testicular cancer. Journal of the National Comprehensive Cancer Network Motzer, R. J., Agarwal, N., Beard, C., Bolger, G. B., Boston, B., Carducci, M. A., Choueiri, T. K., Figlin, R. A., Fishman, M., Hancock, S. L., Hudes, G. R., Jonasch, E., Kessinger, A., Kuzel, T. M., Lange, P. H., Levine, E. G., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Redman, B. G., Robertson, C. N., Schwartz, L. H., Sheinfeld, J., Wang, J. 2009; 7 (6): 672-693

    View details for PubMedID 19555582

  • NCCN clinical practice guidelines in oncology: kidney cancer. Journal of the National Comprehensive Cancer Network Motzer, R. J., Agarwal, N., Beard, C., Bolger, G. B., Boston, B., Carducci, M. A., Choueiri, T. K., Figlin, R. A., Fishman, M., Hancock, S. L., Hudes, G. R., Jonasch, E., Kessinger, A., Kuzel, T. M., Lange, P. H., Levine, E. G., Margolin, K. A., Michaelson, M. D., Olencki, T., Pili, R., Redman, B. G., Robertson, C. N., Schwartz, L. H., Sheinfeld, J., Wang, J. 2009; 7 (6): 618-630

    View details for PubMedID 19555584

  • Mammographic screening in women at increased risk of breast cancer after treatment of Hodgkin's disease BREAST JOURNAL Kwong, A., Hancock, S. L., Bloom, J. R., Pal, S., Birdwell, R. L., Mariscal, C., Ikeda, D. M. 2008; 14 (1): 39-48

    Abstract

    Treatment regimens for Hodgkin's disease (HD) that have included radiation to lymph node regions in the thorax have contributed to high rates of long-term disease-free survival. However, incidental radiation exposure of breast tissue in young women has significantly increased the risk of breast cancer compared to expected rates in the general population. After informing patients about risks associated with previous treatment of HD, we studied screening mammograms and call-back rates in women at increased risk for developing breast cancer at a younger age. We contacted by mail a cohort of 291 women between 25 and 55 years of age who had received thoracic irradiation before 35 years of age for HD with or without chemotherapy. Subjects were offered information about risks identified after HD therapy with questionnaires to assess response to this information. Ten patients refused participation, 93 did not respond, and 21 were excluded after they reported a prior diagnosis of invasive (1) or in situ (2) breast cancer. One hundred and sixty seven women received information about secondary breast cancer risk and were advised to initiate or maintain mammographic screening. Available mammograms were reviewed by two radiologists and classified according to the ACR BI-RADS Mammography Lexicon. Abnormal findings were correlated to pathology results from biopsies. One hundred and fifteen subjects reported that they obtained new mammograms during the period of the study. Ninety-nine were available for secondary review. Patients were studied an average of 16.9 years after HD treatment (Range: 4.5-32.5 years) at an average of 41 years of age (range 25-55 years). High density breast tissue was identified in 60% (60/99). Seventeen of the women (17.2%) were recalled for further imaging. This was more common in women with heterogeneously dense breast tissue. Seven of those recalled (41%) were advised to undergo biopsies that identified ductal carcinoma in situ (DCIS) in one and benign findings in the others. Among 16 women whose mammograms were unavailable for review, three were diagnosed with DCIS; two of these had microscopic evidence of invasive breast cancer. The four in situ or microinvasive cancers were diagnosed in the study participants at 25-40 years of age and from 5 to 23 years after HD therapy. Biopsies were performed because mammograms detected microcalcifications without palpable abnormality in three of these cases. Women who have had thoracic nodal irradiation for Hodgkin's disease have an increased risk of developing secondary breast cancer at an unusually young age. As expected in younger women, high density breast tissue was common on mammography, and the recall and biopsy rates were unusually high. However, early mammographic screening facilitated diagnosis of in situ and early invasive cancer in 3.5% of our subjects.

    View details for Web of Science ID 000252124800006

    View details for PubMedID 18186864

  • Radiotherapy after prostatectomy: Improved biochemical relapse-free survival with whole pelvic compared with prostate bed only for high-risk patients INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Spiotto, M. T., Hancock, S. L., King, C. R. 2007; 69 (1): 54-61

    Abstract

    To compare the biochemical relapse-free survival (bRFS) among patients receiving whole pelvic radiotherapy (WPRT) vs. prostate bed RT (PBRT) after radical prostatectomy.Between 1985 and 2005, 160 patients underwent adjuvant or salvage RT after radical prostatectomy. A short course of total androgen suppression was also given concurrently to 87 patients. Of the 160 patients, 114 were considered at high risk of lymph node involvement because they had a pathologic Gleason score of >/=8, a preoperative prostate-specific antigen level >20 ng/mL, seminal vesicle or prostate capsule involvement, or pathologic lymph node involvement. Of this group, 72 underwent WPRT and 42 underwent PBRT. The median follow-up was >5 years for all patient subsets. Kaplan-Meier and Cox proportional hazards multivariate analyses were performed for all clinical, pathologic, and treatment factors predicting for bRFS.Whole pelvic RT resulted in superior bRFS compared with PBRT (p = 0.03). The advantage of WPRT was limited to high-risk patients, with a 5-year bRFS rate of 47% (95% confidence interval, 35-59%) after WPRT vs. 21% (95% confidence interval, 8-35%) after PBRT (p = 0.008). For low-risk patients, no difference (p = 0.9) was found. On multivariate analysis, only WPRT (p = 0.02) and a preoperative prostate-specific antigen level <1.0 ng/mL (p = 0.002) were significantly associated with bRFS. The benefit from total androgen suppression with postoperative RT was only observed when given concurrently with WPRT (p = 0.04) and not with PBRT (p = 0.4).The results of our study have indicated that WPRT confers superior bRFS compared with PBRT for high-risk patients receiving adjuvant or salvage RT after radical prostatectomy. This advantage was observed only with concurrent TAS. These results are analogous to the benefit from WPRT seen in the Radiation Therapy Oncology Group 94-13 study.

    View details for DOI 10.1016/j.ijrobp.2007.02.035

    View details for Web of Science ID 000248978300009

    View details for PubMedID 17459606

  • A study of the accuracy of cyberknife spinal radiosurgery using skeletal structure tracking. Neurosurgery Ho, A. K., Fu, D., Cotrutz, C., Hancock, S. L., Chang, S. D., Gibbs, I. C., Maurer, C. R., Adler, J. R. 2007; 60 (2): ONS147-56

    Abstract

    New technology has enabled the increasing use of radiosurgery to ablate spinal lesions. The first generation of the CyberKnife (Accuray, Inc., Sunnyvale, CA) image-guided radiosurgery system required implanted radiopaque markers (fiducials) to localize spinal targets. A recently developed and now commercially available spine tracking technology called Xsight (Accuray, Inc.) tracks skeletal structures and eliminates the need for implanted fiducials. The Xsight system localizes spinal targets by direct reference to the adjacent vertebral elements. This study sought to measure the accuracy of Xsight spine tracking and provide a qualitative assessment of overall system performance.Total system error, which is defined as the distance between the centroids of the planned and delivered dose distributions and represents all possible treatment planning and delivery errors, was measured using a realistic, anthropomorphic head-and-neck phantom. The Xsight tracking system error component of total system error was also computed by retrospectively analyzing image data obtained from eleven patients with a total of 44 implanted fiducials who underwent CyberKnife spinal radiosurgery.The total system error of the Xsight targeting technology was measured to be 0.61 mm. The tracking system error component was found to be 0.49 mm.The Xsight spine tracking system is practically important because it is accurate and eliminates the use of implanted fiducials. Experience has shown this technology to be robust under a wide range of clinical circumstances.

    View details for PubMedID 17297377

  • Screening for coronary artery disease after mediastinal irradiation for Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Heidenreich, P. A., Schnittger, I., Strauss, H. W., Vagelos, R. H., Lee, B. K., Mariscal, C. S., Tate, D. J., Horning, S. J., Hoppe, R. T., Hancock, S. L. 2007; 25 (1): 43-49

    Abstract

    Incidental cardiac irradiation during treatment of thoracic neoplasms has increased risks for subsequent acute myocardial infarction or sudden cardiac death. Identifying patients who have a high risk for a coronary event may decrease morbidity and mortality. The objective of this study was to evaluate whether stress imaging can identify severe, unsuspected coronary stenoses in patients who had prior mediastinal irradiation for Hodgkin's disease.We enrolled 294 outpatients observed at a tertiary care cancer treatment center after mediastinal irradiation doses 35 Gy for Hodgkin's disease who had no known ischemic cardiac disease. Patients underwent stress echocardiography and radionuclide perfusion imaging at one stress session. Coronary angiography was performed at the discretion of the physician.Among the 294 participants, 63 (21.4%) had abnormal ventricular images at rest, suggesting prior myocardial injury. During stress testing, 42 patients (14%) developed perfusion defects (n = 26), impaired wall motion (n = 8), or both abnormalities (n = 8). Coronary angiography showed stenosis 50% in 22 patients (55%), less than 50% in nine patients (22.5%), and no stenosis in nine patients (22.5%). Screening led to bypass graft surgery in seven patients. Twenty-three patients developed coronary events during a median of 6.5 years of follow-up, with 10 acute myocardial infarctions (two fatal).Stress-induced signs of ischemia and significant coronary artery disease are highly prevalent after mediastinal irradiation in young patients. Stress testing identifies asymptomatic individuals at high risk for acute myocardial infarction or sudden cardiac death.

    View details for DOI 10.1200/JCO.2006.07.0805

    View details for Web of Science ID 000243725900009

    View details for PubMedID 17194904

  • Testicular cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Motzer, R. J., Bolger, G. B., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Jonasch, E., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pohar, K. S., Redman, B. G., Robertson, C. N., Samlowski, W. E., Sheinfeld, J. 2006; 4 (10): 1038-1058

    View details for PubMedID 17112452

  • Kidney cancer. Clinical practice guidelines in oncology. Journal of the National Comprehensive Cancer Network Motzer, R. J., Bolger, G. B., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Jonasch, E., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pohar, K., Redman, B. G., Robertson, C. N., Samlowski, W. E., Sheinfeld, J. 2006; 4 (10): 1072-1081

    View details for PubMedID 17112454

  • Breast cancer screening in women surviving Hodgkin disease AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS Bloom, J. R., Stewart, S. L., Hancock, S. L. 2006; 29 (3): 258-266

    Abstract

    To inform female Hodgkin disease (HD) survivors, younger than 35 at diagnosis, of their increased risk for breast cancer and encourage them to seek breast cancer screening.An evidence-based intervention, telephone counseling, was used in a pre-post test design, randomized trial with the control group being offered the intervention following the post-test. Women treated at Stanford University who received thoracic irradiation before age 35, alive and HD-free at last contact, were referred to the project (n = 471). Of 261 eligible women who could be located, 157 completed the pretest and were randomized (60% response rate) and 133 completed the post-test (85% retention rate).There was a positive intervention effect on mammography maintenance: the odds of being in maintenance at post-test compared with pretest were greater in the intervention group than in the control group [odds ratio (OR) = 3.6]. Women were more likely to be in mammography maintenance at pre- or post-test if at pretest they were married (OR = 5.7), employed (OR = 2.3), more worried about breast cancer (OR = 1.4 per unit of scale), or received an annual physical examination (OR = 2.2). Women under age 40 were much less likely to be in maintenance than were those age 45 and over (age 35-39, OR = 0.2; under age 35, OR = 0.07).The findings indicate that providing risk information encourages cancer survivors to take health preventive actions. Telephone counseling is a method that can provide risk information and is easily transferable to settings where people seek health information, such as telephone information lines.

    View details for DOI 10.1097/01.coc.0000209447.63640.5a

    View details for Web of Science ID 000238158800008

    View details for PubMedID 16755179

  • Clinical manifestations of noncoronary atherosclerotic vascular disease after moderate dose irradiation CANCER Patel, D. A., Kochanski, J., Suen, A. W., Fajardo, L. F., Hancock, S. L., Knox, S. J. 2006; 106 (3): 718-725

    Abstract

    Accelerated atherosclerosis and carotid stenosis are well-established risks occurring after high radiation doses that are used to treat cancers of the head and neck. Noncoronary vascular disease has been observed and may relate to more moderate dose irradiation.A search of patients treated for Hodgkin disease, non-Hodgkin lymphoma, or seminoma was performed to identify cases with noncoronary vascular complications after irradiation. These three groups were chosen because of the use of intermediate dose radiation and prevalence of long-term survivors. Individual patient records were reviewed to document the type and presentation of the stenosis and the clinical factors that may have contributed to this risk.Twenty-one patients were identified who developed disease in noncoronary arteries after treatment. The median time from irradiation to diagnosis of vascular stenosis was 15 years. Antecedent risk factors for vascular disease were prevalent. Five patients had disease identified by auscultation of bruits before an adverse clinical event occurred. Five patients died from complications related to their vascular disease, which included three deaths after stroke and two after small bowel infarction.Twelve cases arose at an atypically young age for atherosclerotic vascular disease and featured unusual clinical presentations. Nine cases identified occurred at an advanced aged and at a shorter median interval, making a causal relation to irradiation uncertain. Incorporating careful auscultation for bruits in followup evaluation of irradiated patients may identify individuals who are at risk for adverse vascular events. The potential for early vasculopathy in individuals exposed to intermediate dose irradiation suggests a need to manage dyslipidemia and reduce vascular risk factors throughout the posttreatment period.

    View details for DOI 10.1002/cncr.21636

    View details for Web of Science ID 000234822700028

    View details for PubMedID 16353211

  • Diastolic dysfunction after mediastinal irradiation AMERICAN HEART JOURNAL Heidenreich, P. A., Hancock, S. L., Vagelos, R. H., Lee, B. K., Schnittger, I. 2005; 150 (5): 977-982

    Abstract

    Mediastinal irradiation is known to cause cardiac disease, but its effect on left ventricular diastolic function is unknown. The purpose of this study was to determine the prevalence of diastolic dysfunction and its association with prognosis in asymptomatic patients after mediastinal irradiation.We recruited 294 patients who had received at least 35 Gy to the mediastinum for treatment of Hodgkin disease. Each patient underwent resting echocardiography, stress echocardiography, and nuclear scintigraphy. Survival free from cardiac events was determined during 3.2 years of follow-up.The mean age of the included patients was 42 years, and 49% were male. Adequate measurements of diastolic function were obtained in 282 (97%) patients. Diastolic dysfunction was considered mild in 26 (9%) and moderate in 14 (5%). Exercise-induced ischemia was more common in patients with diastolic dysfunction (23%) than those with normal diastolic function (11%, P = .008). After adjustment for patient demographics, clinical characteristics, and radiation history, patients with diastolic dysfunction had worse event-free survival than patients with normal function (hazard ratio 1.66, 95% CI 1.06-2.4).There is a high prevalence of diastolic dysfunction in asymptomatic patients after mediastinal irradiation, and the presence of diastolic dysfunction is associated with stress-induced ischemia and a worse prognosis. Screening with Doppler echocardiography may be helpful in identifying patients at risk for subsequent cardiac events.

    View details for DOI 10.1016/j.ahj.2004.12.026

    View details for Web of Science ID 000233478800024

    View details for PubMedID 16290974

  • Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy EUROPEAN JOURNAL OF HAEMATOLOGY Mauch, P., Ng, A., Aleman, B., Carde, P., Constine, L., Diehl, V., Dinshaw, K., Gospodarowicz, M., Hancock, S., Hodgson, D., Hoppe, R., Liang, R., Loeffler, M., Specht, L., Travis, L. B., Wirth, A., Yahalom, J. 2005; 75: 68-76

    Abstract

    A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas.

    View details for Web of Science ID 000229591400012

    View details for PubMedID 16007872

  • Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY Sinclair, P. A., Hancock, S., Gilmore, W. J., Squires, E. J. 2005; 96 (1): 79-87

    Abstract

    The hepatic metabolism of the 16-androstene steroids was investigated using isolated porcine hepatocytes. This study demonstrated that the liver is capable of producing both phase I and phase II steroid metabolites from 16-androstene steroid precursors. 16-Androstene metabolites were recovered by solid-phase extraction and identified by gas chromatography-mass spectrometry (GC-MS). When 5alpha-androstenone was provided as a substrate, both 3beta- and 3alpha-androstenol were produced as well as a metabolite that showed evidence of hydroxylation. Incubations with the various 16-androstene steroids produced metabolic profiles which suggested that the major role of the liver is phase II conjugation. Sulfoconjugated 16-androstene steroids included androstadienol, 5alpha-androstenone, 3beta-, 3alpha-androstenol, and possibly the hydroxylated metabolite of 5alpha-androstenone. It was determined that hydroxysteroid sulfotransferase (HST) is the likely candidate for the sulfoconjugation of the 16-androstene steroids within the liver. Despite the capacity of the hepatocytes to sulfoconjugate the 16-androstene steroids, the principle metabolites produced from incubations with 5alpha-androstenone, 3beta-, and 3alpha-androstenol were glucuronide conjugates, accounting for approximately 68% of all phase II metabolism. These findings underline the importance of steroid conjugation and suggest that hepatic metabolism of the 16-androstene steroids may influence the levels of 5alpha-androstenone present in the circulation, and thus, capable of accumulating in fat.

    View details for DOI 10.1016/j.jsbmb.2005.01.030

    View details for Web of Science ID 000231480800009

    View details for PubMedID 15896952

  • Testicular cancer. Clinical practice guidelines. Journal of the National Comprehensive Cancer Network Motzer, R. J., Bahnson, R. R., Boston, B., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Redman, B. G., Richey, S., Robertson, C. N., Samlowski, W. E., Sheinfeld, J., Urban, D. A. 2005; 3 (1): 52-76

    View details for PubMedID 19813323

  • Kidney cancer. Clinical practice guidelines. Journal of the National Comprehensive Cancer Network Motzer, R. J., Carducci, M. A., Fishman, M., Hancock, S. L., Hauke, R. J., Hudes, G. R., Kantoff, P., Kuzel, T. M., Lange, P. H., Levine, E. G., Logothetis, C., Margolin, K. A., Pili, R., Pohar, K. S., Redman, B. G., Richey, S., Robertson, C. N., Samlowski, W. E., Sheinfeld, J., Urban, D. A. 2005; 3 (1): 84-93

    View details for PubMedID 19813325

  • A systolic murmur is a common presentation of aortic regurgitation detected by echocardiography CLINICAL CARDIOLOGY Heidenreich, P. A., Schnittger, I., Hancock, S. L., Atwood, J. E. 2004; 27 (9): 502-506

    Abstract

    The finding of aortic regurgitation at a classical examination is a diastolic murmur.Aortic regurgitation is more likely to be associated with a systolic than with a diastolic murmur during routine screening by a noncardiologist physician.In all, 243 asymptomatic patients (mean age 42 +/- 10 years) with no known cardiac disease but at risk for aortic valve disease due to prior mediastinal irradiation (> or = 35 Gy) underwent auscultation by a noncardiologist followed by echocardiography. A systolic murmur was considered benign if it was grade < or = II/VI, not holosystolic, was not heard at the apex, did not radiate to the carotids, and was not associated with a diastolic murmur.Of the patients included, 122 (49%) were male, and 86 (35%) had aortic regurgitation, which was trace in 20 (8%), mild in 52 (21%), and moderate in 14 (6%). A systolic murmur was common in patients with aortic regurgitation, occurring in 12 (86%) with moderate, 26 (50%) with mild, 6 (30%) with trace, and 27 (17%) with no aortic regurgitation (p < 0.0001). The systolic murmurs were classified as benign in 21 (78%) patients with mild and 8 (67%) with moderate aortic regurgitation. Diastolic murmurs were rare, occurring in two (14%) with moderate, two (4%) with mild, and three (2%) with no aortic regurgitation (p=0.15).An isolated systolic murmur is a common auscultatory finding by a noncardiologist in patients with moderate or milder aortic regurgitation. A systolic murmur in patients at risk for aortic valve disease should prompt a more thorough physical examination for aortic regurgitation.

    View details for Web of Science ID 000223604300004

    View details for PubMedID 15471160

  • Radiotherapy after radical prostatectomy: Does transient androgen suppression improve outcomes? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS King, C. R., Presti, J. C., Gill, H., Brooks, J., Hancock, S. L. 2004; 59 (2): 341-347

    Abstract

    The long-term biochemical relapse-free survival and overall survival were compared for patients receiving either radiotherapy (RT) alone or radiotherapy combined with a short-course of total androgen suppression for failure after radical prostatectomy.Between 1985 and 2001, a total of 122 patients received RT after radical prostatectomy at our institution. Fifty-three of these patients received a short-course of total androgen suppression (TAS) 2 months before and 2 months concurrent with RT with a nonsteroidal antiandrogen and an luteinizing hormone-releasing hormone (LHRH) agonist (combined therapy group); the remaining 69 patients received RT alone. Treatment failure was defined after postoperative RT as a detectable PSA >0.05 ng/mL. Clinical and treatment variables examined included: presurgical PSA, clinical T stage, pathologic Gleason sum (pGS), seminal vesicle (SV) involvement, lymph node involvement, surgical margins, pre-RT PSA, prostate dose, pelvic irradiation, indication for postoperative RT (salvage or adjuvant), and time interval between surgery and RT. Minimum follow-up after postoperative RT was 1 year and median follow-up was 5.9 years (maximum, 14 years) for patients receiving RT alone, and 3.9 years (maximum, 11 years) for patients receiving RT with TAS (combined therapy group). Kaplan-Meier analysis was performed for PSA failure-free survival (bNED) and for overall survival (OS). Cox proportional hazards multivariable analysis examined the influence all clinical and treatment variables predicting for bNED and OS.The median time to PSA failure after postoperative RT was 1.34 years for the combined therapy group and 0.97 years for the RT alone group (p = 0.19), with no failures beyond 5 years. At 5 years, the actuarial bNED rates were 57% for the combined therapy group compared with 31% for the RT alone group (p = 0.0012). Overall survival rates at 5 years were 100% for the combined therapy group compared with 87% for the RT alone group (p = 0.0008). For pGS or=8 the 5-year bNED rates were 65% for combined therapy and 17% for RT alone (p = 0.075). The 5-year OS rates for pGS or=8 was 100% for combined therapy and 54% for RT alone (p = 0.04). On multivariable analysis, only SV involvement (p = 0.0145) and the addition of short-course TAS to postoperative RT (p = 0.0019) were significant covariates predicting for bNED and, similarly, approached significance for overall survival (p = 0.0594 and p = 0.0856, respectively).Radiotherapy combined with a short-course TAS after radical prostatectomy appears to confer a PSA relapse-free survival advantage and possibly an overall survival advantage when compared with RT alone. The hypothesis that a transient course of androgen suppression with salvage or adjuvant RT after prostatectomy improves outcomes will need to be tested in a randomized trial.

    View details for DOI 10.1016/j.ijribp.2003.10.015

    View details for Web of Science ID 000221440800002

    View details for PubMedID 15145146

  • Dosimetry and radiobiologic model comparison of IMRT and 3D conformal radiotherapy in treatment of carcinoma of the prostate INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Luxton, G., Hancock, S. L., Boyer, A. L. 2004; 59 (1): 267-284

    Abstract

    Intensity-modulated radiotherapy (IMRT) has introduced novel dosimetry that often features increased dose heterogeneity to target and normal structures. This raises questions of the biologic effects of IMRT compared to conventional treatment. We compared dosimetry and radiobiologic model predictions of tumor control probability (TCP) and normal tissue complication probability (NTCP) for prostate cancer patients planned for IMRT as opposed to standardized three-dimensional conformal radiotherapy (3DCRT).Segmented multileaf collimator IMRT treatment plans for 32 prostate cancer patients were compared to 3DCRT plans for the same patients. Twenty-two received local-field irradiation (LFI), and 10 received extended-field irradiation (EFI) that included pelvic lymph nodes. For LFI, IMRT was planned for delivery of 2 Gy minimum dose to the prostate (> or =99% volume coverage) for 35 fractions. The 3DCRT plans, characterized by more homogenous dose to the target, were designed according to a different protocol to deliver 2 Gy to the center of the prostate for 37 fractions. Mean total dose from 35 fractions of IMRT was equal to mean total dose from 37 fractions of 3DCRT. For EFI, both IMRT and 3DCRT were planned for 2 Gy per fraction to a total dose of 50 Gy to prostate and pelvic lymph nodes, followed by 2 Gy per fraction to 20 Gy to the prostate alone. Treatment dose for EFI-IMRT was defined as minimum dose to the target, whereas for EFI-3DCRT, it was defined as dose to the center of the prostate. TCP was calculated for the prostate in the linear-quadratic model for two choices of alpha/beta. NTCP was calculated with the Lyman model for organs at risk, using Kutcher-Burman dose-volume histogram reduction with Emami parameters.Dose to the prostate, expressed as mean +/- standard deviation, was 74.7 +/- 1.1 Gy for IMRT vs. 74.6 +/- 0.3 Gy for 3D for the LFI plans, and 74.8 +/- 0.6 Gy for IMRT vs. 71.5 +/- 0.6 Gy for 3D for the EFI plans. For the studied protocols, TCP was greater for IMRT than for 3D across the full range of target sensitivity, for both localized- and extended-field irradiation. For LFI, this was due to the smaller number of fractions (35 vs. 37) used for IMRT, and for EFI, this was due to the greater mean dose for IMRT, compared to 3D. For all organs, mean NTCP tended to be lower for IMRT than for 3D, although NTCP values were very small for both 3D and IMRT. Differences were statistically significant for rectum (LFI and EFI), bladder (EFI), and bowel (EFI). For both LFI and EFI, the calculated NTCPs qualitatively agreed with early published clinical data comparing genitourinary and gastrointestinal complications of IMRT and 3D. Present calculations support the hypothesis that accurately delivered IMRT for prostate cancer can limit dose to normal tissue by reducing treatment margins relative to conventional 3D planning, to allow a reduction in complication rate spanning several sensitive structures while maintaining or increasing tumor control probability.

    View details for DOI 10.1016/j.ijrobp.2004.01.024

    View details for Web of Science ID 000221047500034

    View details for PubMedID 15093924

  • Asymptomatic cardiac disease following mediastinal irradiation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Heidenreich, P. A., Hancock, S. L., Lee, B. K., Mariscal, C. S., Schnittger, I. 2003; 42 (4): 743-749

    Abstract

    This study was designed to evaluate the potential benefit of screening previously irradiated patients with echocardiography.Mediastinal irradiation is known to cause cardiac disease. However, the prevalence of asymptomatic cardiac disease and the potential for intervention before symptom development are unknown.We recruited 294 asymptomatic patients (mean age 42 +/- 9 years, 49% men, mean mantle irradiation dose 43 +/- 0.3 Gy) treated with at least 35 Gy to the mediastinum for Hodgkin's disease. After providing written consent, each patient underwent electrocardiography and transthoracic echocardiography. Valvular disease was common and increased with time following irradiation. Patients who had received irradiation more than 20 years before evaluation had significantly more mild or greater aortic regurgitation (60% vs. 4%, p < 0.0001), moderate or greater tricuspid regurgitation (4% vs. 0%, p = 0.06), and aortic stenosis (16% vs. 0%, p = 0.0008) than those who had received irradiation within 10 years. The number needed to screen to detect one candidate for endocarditis prophylaxis was 13 (95% confidence interval [CI] 7 to 44) for patients treated within 10 years and 1.6 (95% CI 1.3 to 1.9) for those treated at least 20 years ago. Compared with the Framingham Heart Study population, mildly reduced left ventricular fractional shortening (<30%) was more common (36% vs. 3%), and age- and gender-adjusted left ventricular mass was lower (90 +/- 27 g/m vs. 117 g/m) in irradiated patients.There is a high prevalence of asymptomatic heart disease in general, and aortic valvular disease in particular, following mediastinal irradiation. Screening echocardiography should be considered for patients with a history of mediastinal irradiation.

    View details for DOI 10.1016/S0735-1097(03)00759-9

    View details for Web of Science ID 000184780600027

    View details for PubMedID 12932613

  • Post-irradiation polyradiculopathy mimics leptomeningeal tumor on MRI NEUROLOGY Hsia, A. W., Katz, J. S., Hancock, S. L., Peterson, K. 2003; 60 (10): 1694-1696

    Abstract

    Three patients with a remote history of Hodgkin's disease treated with total or subtotal lymphoid radiation 17 to 24 years earlier developed lumbosacral polyradiculopathy associated with nodular meningeal enhancement of the conus medullaris and cauda equina on MRI. None had evidence of recurrent Hodgkin's disease or second malignancy, and the MRI findings may be sequelae of radiation therapy.

    View details for Web of Science ID 000183092400033

    View details for PubMedID 12771271

  • Role of beam orientation optimization in intensity-modulated radiation therapy INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Pugachev, A., Li, J. G., Boyer, A. L., Hancock, S. L., Le, Q. T., Donaldson, S. S., Xing, L. 2001; 50 (2): 551-560

    Abstract

    To investigate the role of beam orientation optimization in intensity-modulated radiation therapy (IMRT) and to examine the potential benefits of noncoplanar intensity-modulated beams.A beam orientation optimization algorithm was implemented. For this purpose, system variables were divided into two groups: beam position (gantry and table angles) and beam profile (beamlet weights). Simulated annealing was used for beam orientation optimization and the simultaneous iterative inverse treatment planning algorithm (SIITP) for beam intensity profile optimization. Three clinical cases were studied: a localized prostate cancer, a nasopharyngeal cancer, and a paraspinal tumor. Nine fields were used for all treatments. For each case, 3 types of treatment plan optimization were performed: (1) beam intensity profiles were optimized for 9 equiangular spaced coplanar beams; (2) orientations and intensity profiles were optimized for 9 coplanar beams; (3) orientations and intensity profiles were optimized for 9 noncoplanar beams.For the localized prostate case, all 3 types of optimization described above resulted in dose distributions of a similar quality. For the nasopharynx case, optimized noncoplanar beams provided a significant gain in the gross tumor volume coverage. For the paraspinal case, orientation optimization using noncoplanar beams resulted in better kidney sparing and improved gross tumor volume coverage.The sensitivity of an IMRT treatment plan with respect to the selection of beam orientations varies from site to site. For some cases, the choice of beam orientations is important even when the number of beams is as large as 9. Noncoplanar beams provide an additional degree of freedom for IMRT treatment optimization and may allow for notable improvement in the quality of some complicated plans.

    View details for Web of Science ID 000168781000033

    View details for PubMedID 11380245

  • Hodgkin's Lymphoma: Choice of Therapy and Late Complications. Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program Linch, D. C., Gosden, R. G., Tulandi, T., Tan, S. L., Hancock, S. L. 2000: 205-221

    Abstract

    This review focuses on the different treatment options available for the treatment of Hodgkin's disease, with an emphasis on the importance of the long-term sequelae of these therapies. In Section I, Dr. Linch reviews the current status of Hodgkin's disease treatment. Survival rates have improved over the last three decades due both to better initial therapies and associated supportive care and to the success of salvage therapy. Unlike most other malignancies, a similar survival endpoint can be achieved by different means, e.g., intensive initial therapy resulting in a low relapse rate or less intensive initial therapy and more reliance on salvage therapy. Overall survival has thus become a difficult end-point for clinical trials of primary therapy, and the value of disease-free survival as an end-point can also be questioned. Quality-of-life issues are to the fore of clinical decision and include the psychological trauma of relapse and fertility status. Patient choice is increasingly important. The high level of success in treating Hodgkin's disease also means that attention must be focused on the very long term results and in this context the occurrence of second malignancies is a major issue. In Section II, Dr. Gosden with Dr. Tulandi and Dr. Tan review the risks of infertility following radio-therapy and chemotherapy and address the actions that can be taken to overcome this problem, particularly for females and prepubertal boys and girls. Particular attention is paid to the recent developments in ovarian cryopreservation and harvesting immature germ cells. In Section III, Dr. Hancock gives a comprehensive update of the incidence of secondary acute leukemia, non-Hodgkin's lymphoma and solid tumors in a large population of patients treated for Hodgkin's disease. The roles of radiotherapy, chemotherapy and combined modality treatment as risk factors contributing to the development of these secondary malignancies are reviewed. The importance of efforts to prevent late-occurring solid tumors such as lung cancer through smoking cessation programs and early detection by screening for cancers of the breast, thyroid and skin are emphasized.

    View details for PubMedID 11701543

  • Fractionated stereotactic radiosurgery and preservation of hearing in patients with vestibular schwannoma: A preliminary report NEUROSURGERY Poen, J. C., Golby, A. J., Forster, K. M., Martin, D. P., Chinn, D. M., Hancock, S. L., Adler, J. R. 1999; 45 (6): 1299-1305

    Abstract

    Microsurgery and stereotactic radiosurgery (SRS) for vestibular schwannomas are associated with a relatively high incidence of sensorineural hearing loss. A prospective trial of fractionated SRS was undertaken in an attempt to preserve hearing and minimize incidental cranial nerve injury.Thirty-three patients with vestibular schwannomas were treated with 2100 cGy in three fractions during a 24-hour period using conventional frame-based linear accelerator radiosurgery. The median tumor diameter was 20 mm (range, 7-42 mm). Baseline and follow-up evaluations included audiometry and contrast-enhanced magnetic resonance imaging. End points were tumor progression, preservation of serviceable hearing, and treatment-related complications.Thirty-one patients (32 tumors) were assessable for tumor progression and treatment-related complications and 21 patients for preservation of serviceable hearing, with a median follow-up interval of 2 years (range, 0.5-4.0 yr). Tumor regression or stabilization was documented in 30 patients (97%) and tumor progression in 1 (3%). The patient with tumor progression remains asymptomatic and has not required surgical intervention. Five patients (16%) developed trigeminal nerve injury at a median of 6 months (range, 4-12 mo) after SRS; two of these patients had preexisting trigeminal neuropathy. One patient (3%) developed facial nerve injury (House-Brackmann Class 3) 7 months after SRS. Preservation of useful hearing (Gardner-Robertson Class 1-2) was 77% at 2 years. All patients with pretreatment Gardner-Robertson Class 1 to 2 hearing maintained serviceable (Class 1-3) hearing as of their last follow-up examination.Three-fraction SRS with a conventional stereotactic frame is feasible and well tolerated in the treatment of acoustic neuroma. This study demonstrates a high rate of hearing preservation and few treatment-related complications among a relatively high-risk patient cohort (tumors >15 mm or neurofibromatosis Type 2). Longer follow-up will be required to assess the durability of tumor control.

    View details for Web of Science ID 000084092000010

    View details for PubMedID 10598696

  • The Janeway lecture. Hodgkin's disease--finding the balance between cure and late effects. cancer journal from Scientific American Donaldson, S. S., Hancock, S. L., Hoppe, R. T. 1999; 5 (6): 325-333

    Abstract

    The purpose of this review is to summarize the Stanford experience in Hodgkin's disease, the late effects of treatment, and strategies to improve management to maximize cure and decrease late effects in these patients.Between 1960 and 1999, 2617 consecutive patients with Hodgkin's disease have been seen, treated, and rigorously followed at Stanford. This population includes patients of all ages and stages of disease. The database summarizing this experience serves as the source of survival and mortality data over 4 decades. Two thousand two hundred thirty-two of the population comprise the group evaluated for secondary cardiac disease. Two thousand one hundred sixty-two patients have been evaluated for risk of secondary leukemia, non-Hodgkin's lymphoma, and solid tumors. Eight hundred eighty-five women were evaluated for secondary breast cancer, prompting a subsequent analysis of risk of secondary cancer among 694 pediatric patients.The probability of cure of Hodgkin's disease has dramatically improved over the past 40 years. Today, 94% of patients are expected to survive. Among those who do not survive, approximately half die of Hodgkin's disease, 20% of new cancers, and 14% of cardiovascular complications. Modifications in patient management and treatment have greatly reduced the serious late effects observed from prior therapy. With current combined-modality therapy using moderate doses of involved field of radiation and limited cycles of multiagent, risk adapted chemotherapy, serious cardiac complications and development of secondary cancers are expected to be greatly reduced. The Stanford 25-year pediatric Hodgkin's disease experience reveals that survival in favorable early-stage disease exceeds 95%. Newer protocols for children with advanced-stage disease continue to show these excellent survival rates and promise less late morbidity. Adult protocols using the risk-adapted Stanford V combined-modality program now parallel the pediatric experience, with greater than 90% survival in these patients.Thus today the likelihood of cure of Hodgkin's disease greatly exceeds the risk of late effects, a goal both Dr. Henry Janeway and Madame Marie Curie emphasized and taught from first-hand experience.

    View details for PubMedID 10606471

  • Radiation therapy for clinically localized prostate cancer - A multi-institutional pooled analysis JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Shipley, W. U., Thames, H. D., Sandler, H. M., Hanks, G. E., Zietman, A. L., Perez, C. A., Kuban, D. A., Hancock, S. L., Smith, C. D. 1999; 281 (17): 1598-1604

    Abstract

    Prostate-specific antigen (PSA) evaluation leads to the early detection of both prostate cancer and recurrences following primary treatment. Prostate-specific antigen outcome information on patients 5 or more years following treatment is limited and available mainly as single-institution reports.To assess the likelihood and durability of tumor control using PSA evaluation 5 or more years after radical external beam radiation therapy and to identify pretreatment prognostic factors in men with early prostate cancer treated since 1988, the PSA era.Retrospective, nonrandomized, multi-institutional pooled analysis of patients treated with external beam radiation therapy alone between 1988 and 1995 at 6 US medical centers. Follow-up lasted up to a maximum of 9 years. Outcome data were analyzed using Cox regression and recursive partitioning techniques.A total of 1765 men with stage T1b, T1c, and T2 tumors treated between 1988 and 1995 with external beam radiation. The majority (58%) of patients were older than 70 years and 24.2% had initial PSA values of 20 ng/mL or higher. A minimum of 2 years of subsequent follow-up was required for participation.Actuarial estimates of freedom from biochemical failure.The 5-year estimates of overall survival, disease-specific survival, and the freedom from biochemical failure are 85.0% (95% confidence interval [CI], 82.5%-87.6%), 95.1% (95% CI, 94.0%-96.2%), and 65.8% (95% CI, 62.8%-68.0%), respectively. The PSA failure-free rates 5 and 7 years after treatment for patients presenting with a PSA of less than 10 ng/mL were 77.8% (95% CI, 74.5%-81.3%), and 72.9% (95% CI, 67.9%-78.2%). Recursive partitioning analysis of initial PSA level, palpation stage, and the Gleason score groupings yielded 4 separate prognostic groups: group 1, included patients with a PSA level of less than 9.2 ng/mL; group 2, PSA level of at least 9.2 but less than 19.7 ng/mL; group 3, PSA level at least 19.7 ng/mL and a Gleason score of 2 to 6; and group 4, PSA level of at least 19.7 ng/mL and a Gleason score of 7 to 10. The estimated rates of survival free of biochemical failure at 5 years are 81 % for group 1, 69% for group 2, 47% for group 3, and 29% for group 4. Of the 302 patients followed up beyond 5 years who were free of biochemical disease, 5.0% relapsed from the fifth to the eighth year.Estimated PSA control rates in this pooled analysis are similar to those of single institutions. These rates indicate the probability of success for subsets of patients with tumors of several prognostic category groupings. These results represent a multi-institutional benchmark for evidence-based counseling of prostate cancer patients about radiation treatment.

    View details for Web of Science ID 000080025900023

    View details for PubMedID 10235152

  • Image-guided robotic radiosurgery Neurosurgery Adler, J. R., Murphy, M. J., Chang, S. D., Hancock, S. L. 1999; 44 (6): 1299-306; discussion 1306-7

    Abstract

    PURPOSE: To describe the design and performance of a novel frameless system for radiosurgery. This technology, called image-guided radiosurgery (IGR), eliminates the need for stereotactic frame fixation by relating the identified lesion to radiographic landmarks. CONCEPT: IGR uses a lightweight x-band linear accelerator, computer-controlled robotic arm (Fanuc manipulator [Fanuc Robotics North America, Inc., Rochester Hills, MI]), paired orthogonal x-ray imagers, and a computer workstation that performs rapid image-to-image registration. During radiosurgery, the x-ray imaging system determines the location of the lesion and communicates these coordinates to the robot, which adjusts the pointing of the linear accelerator beam to maintain alignment with the target. RATIONALE: Existing stereotactic techniques require rigid cranial fixation to establish and maintain a system of reference for targeting. Such frames cause pain for the patient, limit the use of fractionation, and necessitate a prolonged period of general anesthesia if children are to be treated. Furthermore, skeletal or any other type of rigid fixation is difficult to achieve beyond the cranium. IGR was designed to overcome these limitations, which are inherent to nearly all current radiosurgical methods. DISCUSSION: Preliminary testing and early clinical experience have demonstrated the practicality and potential of the IGR concept and have identified the most important directions for improvement. For example, an IGR prototype accurately tracked target displacements in three dimensions but showed reduced accuracy when confronted by rotational movements. This observation led to development of a new generation of tracking algorithm that promises to improve tracking in all six dimensions. Further experience indicated that improvements in the quality of the x-ray images were needed to allow the system to locate and treat target sites outside the cranium. Consequently, a new x-ray imaging technology with superior resolution and increased sensitivity has been added to the system. These improvements should make it possible to apply IGR techniques to a variety of targets located throughout the body. This article describes and critiques the components of the IGR and summarizes our preliminary clinical experience.

    View details for PubMedID 10371630

  • Treatment of cavernous sinus tumors with linear accelerator radiosurgery SKULL BASE SURGERY Chang, S. D., Doty, J. R., Martin, D. P., Hancock, S. L., Adler, J. R. 1999; 9 (3): 195-199

    Abstract

    Since 1989, 79 patients with benign or malignant cavernous sinus tumors, have been treated at Stanford University with linear accelerator (linac) radiosurgery. Radiosurgery has been used as (1) a planned second-stage procedure for residual tumor following surgery, (2) primary treatment for patients whose medical conditions preclude surgery, (3) palliation of malignant lesions, and (4) definitive treatment for small, well-localized, poorly accessible tumors. Mean patient age was 52 years (range, 18 to 88); there were 28 males and 51 females. Sixty-one patients had benign tumors; 18 had malignant tumors. Mean tumor volume was 6.8 cm(3) (range 0.5 to 22.5 cm(3)) covered with an average of 2.3 isocenter (range, 1 to 5). Radiation dose averaged 17.1 Gy. Mean follow-up was 46 months. Tumor control or shrinkage, or both, varied with pathology. Radiographic tumor improvement was most pronounced in malignant lesions, with greater than 85% showing reduction in tumor size; benign tumors (meningiomas and schwannomas) had a 63% control rate and 37% shrinkage rate, with none enlarging. We concluded that stereotactic radiosurgery is a valuable tool in managing cavernous sinus tumors. There was excellent control and stabilization of benign tumors and palliation of malignant lesions.

    View details for Web of Science ID 000083016700004

    View details for PubMedID 17171089

  • Clinical experience with image-guided robotic radiosurgery (the Cyberknife) in the treatment of brain and spinal cord tumors NEUROLOGIA MEDICO-CHIRURGICA Chang, S. D., Murphy, M., Geis, P., Martin, D. P., Hancock, S. L., Doty, J. R., Adler, J. R. 1998; 38 (11): 780-783

    Abstract

    The Cyberknife is an image-guided "frameless" dedicated radiosurgical device. This instrument has several distinct advantages over frame-based systems, including improved patient comfort, increased treatment degrees of freedom, and the potential to target extracranial lesions. Clinical results thus far with respect to the treatment of malignant intracranial tumors has been promising. Additionally, the Cyberknife will likely revolutionize the application of radiosurgery to extracranial sites. A description of the components, treatment planning, and clinical results of the Cyberknife will be reviewed.

    View details for Web of Science ID 000077103400031

    View details for PubMedID 9919913

  • Acute hearing loss following fractionated stereotactic radiosurgery for acoustic neuroma - Report of two cases JOURNAL OF NEUROSURGERY Chang, S. D., Poen, J., Hancock, S. L., Martin, D. P., Adler, J. R. 1998; 89 (2): 321-325

    Abstract

    Two cases of acute hearing loss are reported following fractionated stereotactic radiosurgery for acoustic neuroma. Both patients had neurofibromatosis type 2 and were treated with a peripheral tumor dose of 21 Gy delivered in three fractions (7 Gy each) with a minimum interfraction interval of 10 hours. One patient who had previously undergone surgical resection of the treated tumor presented with only rudimentary hearing in the treated ear secondary to an abrupt decrease in hearing prior to treatment. That patient reported total loss of hearing before complete delivery of the third fraction. The second patient had moderately impaired hearing prior to treatment; however, within 10 hours after delivery of the final fraction, he lost all hearing. Both patients showed no improvement in response to glucocorticoid therapy. Possible explanations for this phenomenon are presented.

    View details for Web of Science ID 000074994900022

    View details for PubMedID 9688131

  • Clinical uses of radiosurgery ONCOLOGY-NEW YORK Chang, S. D., Adler, J. R., Hancock, S. L. 1998; 12 (8): 1181-?

    Abstract

    Radiosurgery uses stereotactic targeting methods to precisely deliver highly focused, large doses of radiation to small intracranial tumors and arteriovenous malformations (AVMs). This article reviews the most common clinical applications of radiosurgery and the clinical results reported from a number of series using either a cobalt-60 gamma knife or linear accelerator as radiation sources. Radiosurgery is used to treat malignant tumors, such as selected cases of brain metastases and malignant gliomas (for which stereotactic radiosurgical boosts are utilized in conjunction with fractionated radiation therapy), as well as benign tumors, such as meningiomas, acoustic neuromas, and pituitary adenomas. Treatment of small AVMs is also highly effective. Although radiosurgery has the potential to produce complications, the majority of patients experience clinical improvement with less morbidity than occurs with surgical resection.

    View details for Web of Science ID 000075449300014

    View details for PubMedID 11236310

  • Treatment of hemangioblastomas in von Hippel-Lindau disease with linear accelerator-based radiosurgery NEUROSURGERY Chang, S. D., Meisel, J. A., Hancock, S. L., Martin, D. P., McManus, M., Adler, J. R. 1998; 43 (1): 28-34

    Abstract

    Stereotactic radiosurgery is increasingly being used to treat hemangioblastomas, particularly those that are in surgically inaccessible locations or that are multiple, as is common in von Hippel-Lindau disease. The purpose of this study was to retrospectively evaluate the effectiveness of radiosurgery in the treatment of hemangioblastomas.From 1989 to 1996, 29 hemangioblastomas in 13 patients with von Hippel-Lindau disease were treated with linear accelerator-based radiosurgery. The mean patient age was 40 years (range, 31-57 yr). The radiation dose to the tumor periphery averaged 23.2 Gy (range, 18-40 Gy). The mean tumor volume was 1.6 cm3 (range, 0.07-65.4 cm3). Tumor response was evaluated in serial, contrast-enhanced, computed tomographic and magnetic resonance imaging scans. The mean follow-up period was 43 months (range, 11-84 mo).Only one (3%) of the treated hemangioblastomas progressed. Five tumors (17%) disappeared, 16 (55%) regressed, and 7 (24%) remained unchanged in size. Five of nine patients with symptoms referable to treated hemangioblastomas experienced symptomatic improvement. During the follow-up period, one patient died as a result of progression of untreated hemangioblastomas in the cervical spine. Three patients developed radiation necrosis, two of whom were symptomatic.Although follow-up monitoring is limited, stereotactic radiosurgery provides a high likelihood of local control of hemangioblastomas and is an attractive alternative to multiple surgical procedures for patients with von Hippel-Lindau disease.

    View details for Web of Science ID 000074274500016

    View details for PubMedID 9657185

  • Effect of combined transient androgen deprivation and irradiation following radical prostatectomy for prostatic cancer INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Eulau, S. M., Tate, D. J., Stamey, T. A., Bagshaw, M. A., Hancock, S. L. 1998; 41 (4): 735-740

    Abstract

    To evaluate whether transient androgen deprivation improves outcome in patients irradiated after radical prostatectomy for locally advanced disease, persistent or rising postoperative prostate specific antigen (PSA), or local recurrence.Records of 105 consecutive patients who were treated with pelvic irradiation after radical retropubic prostatectomy between August 1985 and December 1995 were reviewed. Seventy-four patients received radiation alone (mean follow up: 4.6 years), and 31 received transient androgen blockade with a gonadotropin-releasing hormone agonist (4) androgen receptor blocker (1) or both (24) beginning 2 months prior to irradiation (mean follow-up 3.0 years) for a mean duration of 6 months. Two of these patients were excluded from further analysis because they received hormonal therapy for more than 1 year. Patients received a prostatic fossa dose of 60-70 Gy at 2 Gy per fraction; 48 patients also received pelvic nodal irradiation to a median dose of 50 Gy. Survival, freedom from clinical relapse (FFCR), and freedom from biochemical relapse (FFBR) were evaluated by the Kaplan-Meier method. Biochemical relapse was defined as two consecutive PSA measurements exceeding 0.07 ng/ml.At 5 years after irradiation, actuarial survival for all patients was 92%, FFCR was 77%, and FFBR was 34%. FFBR was significantly better among patients who received transient androgen blockade before and during radiotherapy than among those treated with radiation alone (56 vs. 27% at 5 years, p = 0.004). FFCR was also superior for the combined treatment group (100 vs. 70% at 5 years, p = 0.014). Potential clinical prognostic factors before irradiation did not differ significantly between treatment groups, including tumor stage, summed Gleason histologic score, lymph node status, indication for treatment, and PSA levels before surgery or subsequent treatment. Multivariate analysis revealed that transient androgen deprivation was the only significant predictor for biochemical failure.This retrospective study of irradiation after radical prostatectomy suggests that transient androgen blockade and irradiation may improve freedom from early biochemical and clinically evident relapse compared to radiotherapy alone, although more prolonged follow-up will be needed to assess durability of impact upon clinical recurrence and survival rates.

    View details for Web of Science ID 000074327100001

    View details for PubMedID 9652832

  • Treatment of early recurrent prostate cancer with 1,25-dihydroxyvitamin D3 (calcitriol) JOURNAL OF UROLOGY Gross, C., Stamey, T., Hancock, S., Feldman, D. 1998; 159 (6): 2035-2039

    Abstract

    Substantial experimental and epidemiological data indicate that 1,25-dihydroxyvitamin D3 (calcitriol) has potent antiproliferative effects on human prostate cancer cells. We performed an open label, nonrandomized pilot trial to determine whether calcitriol therapy is safe and efficacious for early recurrent prostate cancer. Our hypothesis was that calcitriol therapy slows the rate of rise of prostate specific antigen (PSA) compared with the pretreatment rate.After primary treatment with radiation or surgery recurrence was indicated by rising serum PSA levels documented on at least 3 occasions. Seven subjects completed 6 to 15 months of calcitriol therapy, starting with 0.5 microg. calcitriol daily and slowly increasing to a maximum dose of 2.5 microg. daily depending on individual calciuric and calcemic responses. Each subject served as his own control, comparing the rate of PSA rise before and after calcitriol treatment.As determined by multiple regression analysis, the rate of PSA rise during versus before calcitriol therapy significantly decreased in 6 of 7 patients, while in the remaining man a deceleration in the rate of PSA rise did not reach statistical significance. Overall the decreased rate of PSA rise was statistically significant (p = 0.02 Wilcoxon signed rank test). Dose dependent hypercalciuria limited the maximal calcitriol therapy given (range 1.5 to 2.5 microg. daily).This pilot study provides preliminary evidence that calcitriol effectively slows the rate of PSA rise in select cases, although dose dependent calciuric side effects limit its clinical usefulness. The development of calcitriol analogues with decreased calcemic side effects is promising, since such analogues may be even more effective for treating prostate cancer.

    View details for Web of Science ID 000073584400078

    View details for PubMedID 9598513

  • Node-positive prostatic cancer: Taps or a call to arms? INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hancock, S. L. 1998; 40 (4): 757-759

    View details for Web of Science ID 000072639900001

    View details for PubMedID 9531357

  • Stanford-Kaiser permanente G1 study for clinical stage I to IIA Hodgkin's disease: Subtotal lymphoid irradiation versus vinblastine, methotrexate, and bleomycin chemotherapy and regional irradiation JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Mason, J., Brown, B. W., Hancock, S. L., Baer, D., Rosenberg, S. A. 1997; 15 (5): 1736-1744

    Abstract

    We have demonstrated that a relatively mild chemotherapy regimen, vinblastine, methotrexate, and bleomycin (VBM), and involved-field radiotherapy (IFRT) could substitute for extended-field radiotherapy in patients with favorable Hodgkin's disease (HD) who have been laparotomy-staged. The purpose of this study is to determine if VBM and regional radiotherapy can substitute for extended-field radiotherapy in favorable clinical stage (CS) I and II HD.Seventy-eight patients with favorable CS I to II HD were randomly assigned to subtotal lymphoid irradiation (STLI) or VBM chemotherapy and regional radiotherapy. Randomization was stratified on the basis of age, sex, number of Ann Arbor sites, histology, and institution. Patients were evaluated for freedom from progressive HD, survival, and toxicity. Results were compared with the predecessor trial in pathologically staged patients.With a median follow-up period of 4 years, the rate of freedom from progressive HD was 92% (95% confidence interval [CI], 88% to 96%) for patients treated with STLI and 87% (95% CI, 81% to 93%) for patients treated with VBM and regional radiotherapy. Six of seven patients who relapsed are alive and in remission following successful second-line therapy.Given the caveat of a small number of patients, the results of extended-field radiotherapy and VBM and regional radiotherapy are comparable with a median follow-up period of 4 years. VBM serves as a paradigm to reduce late effects in favorable early-stage HD. We do not advocate its routine use in clinical practice, but instead encourage participation in clinical trials with the objective of maintaining efficacy while reducing toxicity in CS I and II HD.

    View details for Web of Science ID A1997WZ56400006

    View details for PubMedID 9164180

  • The cyberknife: A frameless robotic system for radiosurgery STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Adler, J. R., Chang, S. D., MURPHY, M. J., Doty, J., Geis, P., Hancock, S. L. 1997; 69 (1-4): 124-128

    Abstract

    The Cyberknife is a unique instrument for performing frameless stereotactic radiosurgery. Rather than using rigid immobilization, the Cyberknife relies on an image-to-image correlation algorithm for target localization. Furthermore, the system utilizes a novel, light-weight, high-energy radiation source. The authors describe the technical specifications of the Cyberknife and summarize the initial clinical experience.

    View details for Web of Science ID 000074800300019

    View details for PubMedID 9711744

  • Linear accelerator-based stereotaxic radiosurgery for brain metastases: The influence of number of lesions on survival JOURNAL OF CLINICAL ONCOLOGY Joseph, J., Adler, J. R., Cox, R. S., Hancock, S. L. 1996; 14 (4): 1085-1092

    Abstract

    To evaluate the influence of the number of brain metastases on survival after stereotaxic radiosurgery and factors that affect the risk of delayed radiation necrosis after treatment.Between March 1989 and December 1993, 120 consecutive patients underwent linear accelerator-based stereotaxic radiosurgery for brain metastases identified by computed tomography (CT) or magnetic resonance imaging (MRI) scans. The influence of various clinical factors on outcome was assessed using Kaplan-Meier plots of survival from the date of radiosurgery, and univariate and multivariate analyses.The median survival time was 32 weeks. Progressive brain metastases, both local and regional, caused 25 of 104 deaths. Patients with two metastases (n = 30) or a solitary metastasis (n = 70) had equivalent actuarial survival times (P = .07; median, 37 weeks; maximum, 211+ weeks). Patients treated to three or more metastases (n = 20) had significantly shorter survival times (P < .002; median, 14 weeks; maximum, 63 weeks). Prognostic factors associated with prolonged survival included a pretreatment Karnofsky performance status > or = 70% and fewer than three metastases. Delayed radiation necrosis at the treated site developed in 20 patients and correlated with prior or concurrent delivery of whole-brain irradiation and the logarithm of the tumor volume.Survival duration is equivalent for patients with one or two brain metastases and is similar to that reported for patients with a solitary metastasis managed by surgical resection and whole-brain irradiation. Survival after radiosurgery for three or more metastases was similar to that reported for whole-brain irradiation.

    View details for Web of Science ID A1996UF06800007

    View details for PubMedID 8648361

  • Second cancers after Hodgkin's disease in childhood NEW ENGLAND JOURNAL OF MEDICINE Donaldson, S. S., Hancock, S. L. 1996; 334 (12): 792-794

    View details for Web of Science ID A1996TZ97900010

    View details for PubMedID 8592556

  • Long-Term Complications of Treatment and Causes of Mortality After Hodgkin's Disease. Seminars in radiation oncology Hancock, S. L., Hoppe, R. T. 1996; 6 (3): 225-242

    Abstract

    The majority of newly diagnosed patients are expected to survive Hodgkin's disease because of effective therapies established during past 30 years. Long-term observations from large populations of treated patients have disclosed a variety of late effects of the disease and its therapy have contributed morbidity and excess mortality to Hodgkin's disease survivors. Secondary cancers have continued to accrue, and the risk relative to the general population has increased to 6.4 (95% confidence intervals: 5.5 to 7.3) in updated experience at Stanford University. Risks are significantly elevated for leukemia (primarily after chemotherapy regimens containing alkylating agents); non-Hodgkin's lymphoma; and tumors of the lung, breast, soft tissues, bone, stomach, pancreas, salivary gland, thyroid, and cutaneous melanoma. Early cardiovascular disease has also been observed and numerically exceeds second cancers as a cause of death in patients with early stage Hodgkin's disease (49 v 47 cases). Pulmonary dysfunction, thyroid dysfunction, infertility, psychosocial changes, gastrointestinal problems, soft-tissue changes, alterations in immunity, and risks for infection have also affected some treated patients. As these problems have been recognized, treatment approaches have been modified over the last 10 to 15 years, and early data suggest a decrease in some treatment sequellae.

    View details for PubMedID 10717180

  • PROSTATE-SPECIFIC ANTIGEN AFTER RADIOTHERAPY FOR PROSTATE-CANCER - A REEVALUATION OF LONG-TERM BIOCHEMICAL CONTROL AND THE KINETICS OF RECURRENCE IN PATIENTS TREATED AT STANFORD-UNIVERSITY JOURNAL OF UROLOGY Hancock, S. L., Cox, R. S., Bagshaw, M. A. 1995; 154 (4): 1412-1417

    Abstract

    We evaluated prostate specific antigen (PSA) evidence for control of prostatic cancer after irradiation.We studied 110 patients for whom more than 2 PSA measurements were obtained to establish trends and the initial measurement was done between April 1985 and January 1988.A total of 42 patients (38%) had stable, normal PSA levels with followup averaging 12.4 years (range 4.4 to 24.8). Increasing clinical stage or Gleason score correlated significantly with risk for PSA relapse, as did pretreatment PSA level. Short PSA doubling times were associated with distant metastasis rather than with local recurrence.We found that irradiation durably controlled 38% of prostatic cancers of various stages and grades and is unlikely to accelerate tumor growth.

    View details for Web of Science ID A1995RU47200042

    View details for PubMedID 7544843

  • BRIEF CHEMOTHERAPY, STANFORD-V, AND ADJUVANT RADIOTHERAPY FOR BULKY OR ADVANCED-STAGE HODGKINS-DISEASE - A PRELIMINARY-REPORT JOURNAL OF CLINICAL ONCOLOGY Bartlett, N. L., Rosenberg, S. A., Hoppe, R. T., Hancock, S. L., Horning, S. J. 1995; 13 (5): 1080-1088

    Abstract

    Although survival rates have improved for patients with bulky and advanced-stage Hodgkin's disease (HD), current treatments entail substantial acute morbidity and risks for late effects such as infertility, second malignancies, and cardiopulmonary toxicities. A novel, brief chemotherapy regimen (doxorubicin, vinblastine, mechlorethamine, vincristine, bleomycin, etoposide, and prednisone [Stanford V]) was designed to shorten the duration of treatment, significantly reduce cumulative doses of alkylating agents, doxorubicin, and bleomycin, and maintain dose-intensity (DI). This brief chemotherapy was combined with radiation therapy (RT) to bulky disease sites.Since May 1989, 65 previously untreated patients were treated for stage II HD with bulky mediastinal involvement (n = 21) or for stage III or IV HD (n = 44). Patients received weekly chemotherapy for 12 weeks. Consolidative RT was given to the first 25 patients to sites of initial bulky disease or radiographic abnormalities that persisted after chemotherapy; in the remaining 40 patients, RT was limited to bulky disease (adenopathy > or = 5 cm and/or macroscopic splenic nodules defined by computed tomography [CT]).With a median follow-up period of 2 years, actuarial 3-year survival rate is 96% and failure-free survival (FFS) rate is 87%. The 3-year FFS rate is 100% for stage II patients with bulky mediastinal disease and 82% for patients with stage III to IV disease. There were no treatment-related deaths. In a preliminary analysis on a subset of patients, female and male fertility appears to be preserved.These preliminary results indicate that the Stanford V chemotherapy regimen with or without RT is well-tolerated and effective therapy for bulky, limited-stage, and advanced-stage HD. Less cumulative exposure to alkylating agents, doxorubicin, and bleomycin and limited use of radiation is expected to decrease risks for second neoplasms and late cardiopulmonary toxicity. Based on these results, the Stanford V chemotherapy with or without RT regimen deserves further study in the context of a randomized clinical trial.

    View details for Web of Science ID A1995QV95100006

    View details for PubMedID 7537796

  • STEM-CELL FACTOR ENHANCES THE SURVIVAL OF MURINE INTESTINAL STEM-CELLS AFTER PHOTON IRRADIATION RADIATION RESEARCH Leigh, B. R., Khan, W., Hancock, S. L., Knox, S. J. 1995; 142 (1): 12-15

    Abstract

    Recombinant rat stem cell factor (SCF) has been shown to decrease lethality in mice exposed to total-body irradiation (TBI) in the lower range of lethality through radioprotection of hematopoietic stem cells and acceleration of bone marrow repopulation. This study evaluates the effect of SCF on the survival of the intestinal mucosal stem cell after TBI. This non-hematopoietic stem cell is clinically relevant. Gastrointestinal toxicity is common during and after abdominal and pelvic radiation therapy and limits the radiation dose in these regions. As observed with bone marrow, the administration of SCF to mice prior to TBI enhanced the survival of mouse duodenal crypt stem cells. The maximum enhancement of survival was seen when 100 micrograms/kg of SCF was given intraperitoneally 8 h before irradiation. This regimen increased the survival of duodenal crypt stem cells after 12.0 Gy TBI from 22.5 +/- 0.7 per duodenal cross section for controls to 30.0 +/- 1.7 after treatment with SCF (P = 0.03). The TBI dose producing 50% mortality at 6 days (LD50/6) was increased from 14.9 Gy for control mice to 19.0 Gy for mice treated with SCF (dose modification factor = 1.28). These findings demonstrate that SCF has radioprotective effects on a non-hematopoietic stem cell population and suggest that SCF may be of clinical value in preventing radiation injury to the intestine.

    View details for Web of Science ID A1995QP25100002

    View details for PubMedID 7534934

  • STEM-CELL FACTOR ENHANCES THE SURVIVAL OF IRRADIATED HUMAN BONE-MARROW MAINTAINED IN SCID MICE STEM CELLS Leigh, B. R., Webb, S., Hancock, S. L., Knox, S. J. 1994; 12 (4): 430-435

    Abstract

    The effect of recombinant human stem cell factor (SCF) on the response of human fetal bone marrow progenitor cells to irradiation was studied using immunodeficient mice with human fetal bone grafts (SCID/Hu mice). SCID/Hu mice were treated with three intraperitoneal injections of 500 micrograms/kg SCF at 20 h before, two h before, and four h after 100 cGy total body irradiation. Fourteen days following irradiation, the fetal bone grafts were harvested and studied. Most of the isolated bone marrow cells were human, as determined by flow cytometry. Colony forming assays were performed on the bone marrow to determine the survival of erythroid (BFU-E) and myeloid (CFU-GM) precursor cells. A statistically significant increase in BFU-E and CFU-GM survival after irradiation was observed for bone marrow maintained in the SCF treated mice when compared to bone marrow from mice not treated with SCF. The enhancement in colony forming unit survival after irradiation ranged from 4.3-fold for BFU-E (p = 0.05) to 13.1-fold for CFU-GM (p = 0.002). These findings suggest that SCF may be of potential clinical value for the prevention of radiation-induced myelosuppression.

    View details for Web of Science ID A1994NY15600010

    View details for PubMedID 7524895

  • COMPUTED-TOMOGRAPHY ASSESSMENT OF SPLENIC SIZE AS A PREDICTOR OF SPLENIC WEIGHT AND DISEASE INVOLVEMENT IN LAPAROTOMY STAGED HODGKINS-DISEASE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Hancock, S. L., SCIDMORE, N. S., Hopkins, K. L., Cox, R. S., Bergin, C. J. 1994; 28 (1): 93-99

    Abstract

    To evaluate how well splenic size predicts the risk of splenic Hodgkin's disease and to assess how accurately splenic dimensions on computerized tomographic scans predict spleen size and involvement by Hodgkin's disease.Splenic weights were obtained from laparotomies performed on 897 patients who presented with Hodgkin's disease and were compared with histologic involvement using logistic regression. Splenic dimensions were measured from preoperative computerized tomographic scans in 94 of these patients, and unidimensional splenic measurements [length (L), width (W), thickness (T)] and their products were compared with splenic weight at laparotomy using linear regression.Hodgkin's disease involved 42% of the spleens at laparotomy and 31% of those assessed by computerized tomography. Splenic weight averaged 198 +/- 5 g (range 40-2000 g). Weight and involvement were greater with "unfavorable" histologies (mixed cellularity, lymphocyte depletion, and unclassified Hodgkin's disease: 229 +/- 12 g; 62.7% involved) than with "favorable" histologies (nodular sclerosing, lymphocyte predominant, and interfollicular Hodgkin's disease: 191 +/- 5 g; 37.8% involved). Splenic weight was the strongest independent risk factor correlated with Hodgkin's disease in univariate and multivariate analyses in all patients and the only identifiable univariate risk factor among those with computerized tomographic scans. For most patients, however, splenic weight poorly predicted involvement: The probability of involvement never fell below 20% and exceeded 80% when splenic weight exceeded 270 g with unfavorable histologies or 685 g in favorable histologies. Spleens of average weight had a probability of involvement of 36% with favorable histologies, 70% with unfavorable histologies. Unidimensional measurements of the spleen on computed tomography correlated poorly with splenic weight, but their product correlated well (Correlation coefficients: L: 0.73; W: 0.65; T: 0.78; [0.344485 x L x W x T]: 0.94).Splenic weight is the strongest factor correlating with the risk of splenic involvement by Hodgkin's disease and can be accurately estimated from three-dimensional measurements on computed tomographic scans, but not from unidimensional measurements. However, splenic weight is not a sensitive predictor of involvement of the spleen by Hodgkin's disease. Therefore, treatment approaches to Hodgkin's disease must be based upon intermediate risks of splenic involvement for most clinically staged patients.

    View details for Web of Science ID A1994MP35300012

    View details for PubMedID 8270463

  • FACTORS AFFECTING LATE MORTALITY FROM HEART-DISEASE AFTER TREATMENT OF HODGKINS-DISEASE JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Hancock, S. L., TUCKER, M. A., Hoppe, R. T. 1993; 270 (16): 1949-1955

    Abstract

    To assess the risk of death from heart disease after Hodgkin's disease therapy.Retrospective study comparing treated patients with a matched general population.Referral center.A total of 2232 consecutive Hodgkin's disease patients treated from 1960 through 1991. Follow-up averaged 9.5 years.Relative risks (RRs), the ratio of the observed to the expected cases with 95% confidence intervals (CIs), chi tests for trends, and Kaplan-Meier actuarial risks.Of the 2232 patients, 88 (3.9%) died of heart disease, 55 from acute myocardial infarction and 33 from other cardiac diseases, including congestive heart failure, radiation pericarditis or pancarditis, cardiomyopathy, or valvular heart disease. The RR for cardiac death was 3.1 (CI, 2.4 to 3.7). Mediastinal radiation of 30 Gy or less (n = 385 patients) did not increase risk; above 30 Gy (n = 1830), RR was 3.5 (CI, 2.7 to 4.3). Blocking to limit cardiac exposure reduced the RR for other cardiac diseases from 5.3 (CI, 3.1 to 7.5) to 1.4 (CI, 0.6 to 2.9), but not acute myocardial infarction (RR, 3.7 vs 3.4). The RRs increased with duration after treatment (trend in acute myocardial infarction, P = .02; in other cardiac diseases, P = .004). The RR for acute myocardial infarction was highest after irradiation before 20 years of age and decreased with increasing age at treatment (P < .0001 for trend).Mediastinal irradiation for Hodgkin's disease increases the risk of subsequent death from heart disease. Risk increased with high mediastinal doses, minimal protective cardiac blocking, young age at irradiation, and increasing duration of follow-up.

    View details for Web of Science ID A1993MC51300026

    View details for PubMedID 8411552

  • THE EFFECT OF STEM-CELL FACTOR ON IRRADIATED HUMAN BONE-MARROW CANCER RESEARCH Leigh, B. R., Hancock, S. L., Knox, S. J. 1993; 53 (17): 3857-3859

    Abstract

    This study evaluates the effect of recombinant human stem cell factor (SCF) on the in vitro response of human bone marrow progenitor cells to irradiation. Light density nonadherent mononuclear cells were isolated from human bone marrow and resuspended in either semisolid culture or liquid culture with or without 100 ng/ml SCF. After 24 h in culture, cells were irradiated and assessed for survival of erythroid burst-forming unit, granulocyte colony-forming unit(s), or granulocyte-macrophage colony-forming unit precursors in the presence of erythropoietin, granulocyte colony-stimulating factor, or granulocyte-macrophage colony-stimulating factor, respectively. Incubation with SCF prior to irradiation (0-300 cGy) resulted in an increase in both absolute colony number and surviving fraction for erythroid burst-forming units, granulocyte colony-forming units, and granulocyte-macrophage colony-forming units as compared to cultures that did not contain SCF. The mean surviving fraction enhancement ratio after 100 cGy ranged from 1.2 to 3.7. An increased fraction of CD34+ progenitors in S-phase after exposure to SCF may explain in part the apparent radioprotective effect of SCF on human bone marrow progenitor cells.

    View details for Web of Science ID A1993LU57900003

    View details for PubMedID 7689418

  • CARDIAC DISEASE FOLLOWING TREATMENT OF HODGKINS-DISEASE IN CHILDREN AND ADOLESCENTS JOURNAL OF CLINICAL ONCOLOGY Hancock, S. L., Donaldson, S. S., Hoppe, R. T. 1993; 11 (7): 1208-1215

    Abstract

    Cardiac disease is second only to neoplastic disease as a cause of death after treatment for Hodgkin's disease. This study evaluates the risks of cardiac disease following treatment of Hodgkin's disease during childhood and adolescence.We reviewed records of 635 patients treated for Hodgkin's disease before 21 years of age at Stanford University between 1961 and 1991. Mean age was 15.4 years; mean follow-up duration was 10.3 years, representing 6,564 person-years of observation. Relative risks (RRs) of death from cardiac diseases were calculated by comparison with age-, sex-, and race-matched general population rates from United States decennial life-tables.Twelve patients have died of cardiac disease (RR, 29.6; 95% confidence interval [CI], 16.0 to 49.3), including seven deaths from acute myocardial infarction ([AMI] RR, 41.5; 95% CI, 18.1 to 82.1), three from valvular heart disease, and two from radiation pericarditis/pancarditis. Thus far, the risk of AMI death was comparable after radiation alone (RO) or after chemotherapy and radiation (CM) (RO-AMI RR, 52.2; 95% CI, 21.1 to 108.7; CM-AMI RR, 21.1; 95% CI, 0.0 to 104.4; P = .6). The risk for other cardiac death (CD) tended to be higher after combined treatment (RO-non-AMI RR, 7.4; 95% CI, 0.0 to 36.5; CM-non-AMI RR, 45.8; 95% CI, 14.4 to 110.6; P = .1). Deaths occurred 3 to 22 years after patients received 42 to 45 Gy to the mediastinum between 9 and 20 years of age. There have been no deaths among patients treated to lower mediastinal radiation doses or without mediastinal radiation. There are no clear trends in the latency of risk. One hundred six nonfatal abnormalities have also been diagnosed.Mediastinal radiation of 40 to 45 Gy increases the risk of death from coronary artery and other cardiac diseases. The risk increases within 5 years of irradiation. These observations support combined-modality, low-dose irradiation regimens in children and adolescents and suggest the need for careful cardiac screening of treated patients.

    View details for Web of Science ID A1993LL23300003

    View details for PubMedID 8315419

  • BREAST-CANCER AFTER TREATMENT OF HODGKINS-DISEASE JOURNAL OF THE NATIONAL CANCER INSTITUTE Hancock, S. L., TUCKER, M. A., Hoppe, R. T. 1993; 85 (1): 25-31

    Abstract

    Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings.This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment.To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race.Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0).Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy.The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.

    View details for Web of Science ID A1993KF02900011

    View details for PubMedID 8416252

  • THYROID-DISEASES AFTER TREATMENT OF HODGKINS-DISEASE NEW ENGLAND JOURNAL OF MEDICINE Hancock, S. L., Cox, R. S., McDougall, I. R. 1991; 325 (9): 599-605

    Abstract

    Thyroid disease, especially hypothyroidism, is common in patients with Hodgkin's disease who have been treated with irradiation. We reviewed the records of 1787 patients (740 women and 1047 men) with Hodgkin's disease who were treated with radiation therapy alone (810 patients), radiation and chemotherapy (920 patients), or chemotherapy alone (57 patients) at Stanford University between 1961 and 1989. Among these patients, 1533 were alive at the last follow-up, and 254 had died of causes other than Hodgkin's disease. (Four other patients were excluded from the analysis because they had undergone thyroidectomy before treatment for Hodgkin's disease. The thyroid was irradiated in 1677 patients. Follow-up averaged 9.9 years.A total of 573 patients had clinical or biochemical evidence of thyroid disease. Among the 1677 patients whose thyroid was irradiated, the actuarial risk of thyroid disease 20 years after treatment was 52 percent, and it was 67 percent at 26 years. Hypothyroidism was found in 513 patients. A total of 486 patients received thyroxine therapy for elevated serum thyrotropin concentrations and either low free thyroxine (208 patients) or normal free thyroxine values (278 patients); 27 had transient elevations of the serum thyrotropin level that were not treated. Graves' hyperthyroidism developed in 30 patients (2 of whom had not undergone thyroid irradiation), and ophthalmopathy developed in 17 of these patients. Ophthalmopathy developed in four other patients with Graves' disease during a period of hypothyroidism (n = 3) or euthyroidism (n = 1). The risk of Graves' disease was 7.2 to 20.4 times that for normal subjects. Silent thyroiditis with thyrotoxicosis developed in six patients. Forty-four patients were found to have single or multiple thyroid nodules, 26 of whom underwent thyroidectomy. Six of the 44 had papillary or follicular cancers. Among the patients who did not undergo operation, 12 had small functioning nodules, 4 had cysts, and 2 had multinodular goiters. The actuarial risk of thyroid cancer was 1.7 percent. The risk of thyroid cancer was 15.6 times the expected risk.High risks of thyroid disease persist more than 25 years after patients have received radiation therapy for Hodgkin's disease, reinforcing the need for continued clinical and biochemical evaluation. Prolonged follow-up confirms an elevated risk of thyroid cancer and Graves' disease as well as hypothyroidism in these patients.

    View details for Web of Science ID A1991GC32800002

    View details for PubMedID 1861693

  • INTERLEUKIN-1-BETA INITIALLY SENSITIZES AND SUBSEQUENTLY PROTECTS MURINE INTESTINAL STEM-CELLS EXPOSED TO PHOTON RADIATION CANCER RESEARCH Hancock, S. L., Chung, R. T., Cox, R. S., KALLMAN, R. F. 1991; 51 (9): 2280-2285

    Abstract

    Interleukin 1 (IL-1) has been shown to prevent early bone marrow-related death following total-body irradiation, by protecting hematopoietic stem cells and speeding marrow repopulation. This study assesses the effect of IL-1 on the radiation response of the intestinal mucosal stem cell, a nonhematopoietic normal cell relevant to clinical radiation therapy. As observed with bone marrow, administration of human recombinant IL-1 beta (4 micrograms/kg) to C3H/Km mice 20 h prior to total-body irradiation modestly protected duodenal crypt cells. In contrast to bone marrow, IL-1 given 4 or 8 h before radiation sensitized intestinal crypt cells. IL-1 exposure did not substantially alter the slope of the crypt cell survival curve but did affect the shoulder: the X-ray survival curve was offset to the right by 1.01 +/- 0.06 Gy when IL-1 was given 20 h earlier and by 1.28 +/- 0.08 Gy to the left at the 4-h interval. Protection was greatest when IL-1 was administered 20 h before irradiation, but minimal effects persisted as long as 7 days after a single injection. The magnitude of radioprotection at 20 h or of radiosensitization at 4 h increased rapidly as IL-1 dose increased from 0 to 4 micrograms/kg. However, doses ranging from 10 to 100 micrograms/kg produced no further difference in radiation response. Animals treated with saline or IL-1 had similar core temperatures from 4 to 24 h after administration, suggesting that thermal changes were not responsible for either sensitization or protection. Mice irradiated 20 h after IL-1 had significantly greater crypt cell survival than saline-treated irradiated controls at all assay times, which ranged from 54 to 126 h following irradiation. The intervals to maximum crypt depopulation and initiation of repopulation were identical in both saline- and IL-1-treated groups, suggesting that IL-1 altered absolute stem cell survival but not the kinetics of repopulation.

    View details for Web of Science ID A1991FJ82100006

    View details for PubMedID 2015592

  • FINAL REPORT OF THE PHASE-I TRIAL OF THE HYPOXIC CELL RADIOSENSITIZER SR-2508 (ETANIDAZOLE) RADIATION-THERAPY ONCOLOGY GROUP-83-03 INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Coleman, C. N., Wasserman, T. H., Urtasun, R. C., Halsey, J., Noll, L., Hancock, S., Phillips, T. L. 1990; 18 (2): 389-393

    Abstract

    In a Phase I trial SR 2508 was administered by rapid intravenous infusion to 102 patients receiving radiation therapy. The dose-limiting toxicity was peripheral sensory neuropathy (PN) which was related to the cumulative dose administered. The highest single daily dose, 3.7 g/m2, was tolerated without toxicity. The lowest cumulative toxic dose was 21.6 g/m2, and the highest non-toxic dose was 40.8 g/m2. Grade 1 neuropathies were mild and self-limited; grade 2 neuropathies were long-lasting and debilitating. In a retrospective analysis, the risk of developing neurotoxicity was related to the cumulative drug exposure calculated by the area-under-the-curve (AUC) of plasma concentration versus time. There was an increased incidence of neuropathy in patients with a cumulative AUC of greater than or equal to 36 mM-hr. At a total dose of 34 g/m2 over 6 weeks, the incidence of Grade 1 neuropathy was approximately 30%; no grade 2 neuropathy occurred at this dose and schedule. Additional toxicities observed included nausea and vomiting (6%), skin rash (4%), and transient arthralgias (3%). One patient had transient abnormalities in liver function tests of unknown etiology. (In a more recent Phase II trial neutropenia has been observed which may be related to SR2508). Approximately three times more SR 2508 is tolerable compared to misonidazole, and it appears that severe neuropathy can be avoided by monitoring individual patient pharmacokinetic parameters. Evaluation of the efficacy of this hypoxic cell sensitizer is in progress.

    View details for Web of Science ID A1990CR71000017

    View details for PubMedID 2154420

  • Current Stanford clinical trials for Hodgkin's disease. Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer Hoppe, R. T., Horning, S. J., Hancock, S. L., Rosenberg, S. A. 1989; 117: 182-190

    View details for PubMedID 2690227

  • VINBLASTINE, BLEOMYCIN, AND METHOTREXATE - AN EFFECTIVE ADJUVANT IN FAVORABLE HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Hancock, S. L., Rosenberg, S. A. 1988; 6 (12): 1822-1831

    Abstract

    Sixty-seven patients with favorable pathologic stage (PS) I and IIA or B or IIIA Hodgkin's disease were randomized to receive subtotal or total lymphoid irradiation (STLI/TLI) alone or involved field irradiation (IF) plus six cycles of a novel adjuvant chemotherapy containing vinblastine, bleomycin, and methotrexate (VBM). With a follow-up from 6 to 72 months (median, 37 months), the actuarial freedom-from-progressive disease (FFP) at 5 years is 70% after STLI/TLI and 95% after IF plus VBM. One death has occurred in the irradiation-only treatment group. The data for IF plus VBM are significantly superior to previous actuarial results at 5 years using IF alone (FFP = 35%, P less than .00001) and compare favorably with prior results with IF plus nitrogen mustard, vincristine, procarbazine, +/- prednisone (MOP[P]) chemotherapy (FFP = 80% at 5 years, P = .10). VBM is well tolerated with greater than 90% of calculated doses delivered. As anticipated, VBM has had relatively little adverse effect on male or female fertility. Selected pulmonary functions are reduced early after IF plus VBM to a greater degree than with irradiation of the mediastinum alone, but the differences are modest. Based upon our current numbers and follow-up, we can be 90% confident that VBM as an adjuvant to irradiation in favorable Hodgkin's disease is as effective, or even superior, to MOP(P) chemotherapy. Because of its lesser toxicity, adjuvant VBM may have a broader role in the management of Hodgkin's disease.

    View details for Web of Science ID A1988R308000006

    View details for PubMedID 2462025

  • INTERCURRENT DEATH AFTER HODGKIN DISEASE THERAPY IN RADIOTHERAPY AND ADJUVANT MOPP TRIALS ANNALS OF INTERNAL MEDICINE Hancock, S. L., Hoppe, R. T., Horning, S. J., Rosenberg, S. A. 1988; 109 (3): 183-189

    Abstract

    To assess long-term differences in mortality associated with initial Hodgkin disease therapy.Retrospective review of patients treated in prospectively randomized clinical trials.Three hundred twenty-six patients with pathologic stage I, II, or III, A or B Hodgkin disease treated between 1967 and 1980 with median follow-up exceeding 14 years.Patients at the same stage of disease were randomized to receive radiation alone (167 patients) or radiation followed by 6 cycles of mechlorethamine hydrochloride, vincristine, procarbazine, and prednisone (MOPP) chemotherapy (159 patients) with additional therapy for progression or recurrence.No significant differences between treatment regimens for actuarial survival, intercurrent disease, or Hodgkin disease mortality were seen. Thirty-three patients who received radiation alone and 30 patients who received adjuvant chemotherapy died without evident Hodgkin disease. Death was caused by second neoplasms in 28 patients (relative risk, 2.35; 95% CI, 1.46 to 3.24). Six patients developed acute myelogenous leukemia or a myeloproliferative disorder after treatment including MOPP. Chemotherapy exposure varied among the 8 patients with lung cancers, 6 with gastrointestinal and 3 with other adenocarcinomas, 3 with sarcomas, 1 with diffuse large cell lymphoma, and 1 with melanoma. Acute myocardial infarction caused 9 of 17 cardiovascular disease deaths with 5 occurring in patients between the ages of 33 and 43. Nonetheless, the risk for acute myocardial infarction was not clearly increased (relative risk, 0.86; 95% CI, 0.42 to 1.57). Fifteen patients died from infection: 5, opportunistic; 5, asplenic sepsis; and 5, other pneumonias. Two patients died in accidents, and 1 died from radiation pneumonitis.Adjuvant MOPP chemotherapy improved freedom from relapse without significant survival benefit or impairment. Leukemogenesis was the only lethal complication associated with MOPP. Survivors of Hodgkin disease had an increased risk for death from a second neoplasm, but no apparent increased risk for death from acute myocardial infarction.

    View details for Web of Science ID A1988P606500005

    View details for PubMedID 3291657

Conference Proceedings


  • Management of breast cancer after Hodgkin's disease Wolden, S. L., Hancock, S. L., Carlson, R. W., Goffinet, D. R., Jeffrey, S. S., Hoppe, R. T. AMER SOC CLINICAL ONCOLOGY. 2000: 765-772

    Abstract

    To evaluate the incidence, detection, pathology, management, and prognosis of breast cancer occurring after Hodgkin's disease.Seventy-one cases of breast cancer in 65 survivors of Hodgkin's disease were analyzed.The median age at diagnosis was 24.6 years for Hodgkin's disease and 42.6 years for breast cancer. The relative risk for invasive breast cancer after Hodgkin's disease was 4.7 (95% confidence interval, 3.4 to 6. 0) compared with an age-matched cohort. Cancers were detected by self-examination (63%), mammography (30%), and physician exam (7%). The histologic distribution paralleled that reported in the general population (85% ductal histology) as did other features (27% positive axillary lymph nodes, 63% positive estrogen receptors, and 25% family history). Although 87% of tumors were less than 4 cm, 95% were managed with mastectomy because of prior radiation. Two women underwent lumpectomy with breast irradiation. One of these patients developed tissue necrosis in the region of overlap with the prior mantle field. The incidence of bilateral breast cancer was 10%. Adjuvant systemic therapy was well tolerated; doxorubicin was used infrequently. Ten-year disease-specific survival was as follows: in-situ disease, 100%; stage I, 88%; stage II, 55%; stage III, 60%; and stage IV, zero.The risk of breast cancer is increased after Hodgkin's disease. Screening has been successful in detecting early-stage cancers. Pathologic features and prognosis are similar to that reported in the general population. Repeat irradiation of the breast can lead to tissue necrosis, and thus, mastectomy remains the standard of care in most cases.

    View details for Web of Science ID 000085401800008

    View details for PubMedID 10673517

  • Gastrointestinal cancer after treatment of Hodgkin's disease Birdwell, S. H., Hancock, S. L., Varghese, A., Cox, R. S., Hoppe, R. T. ELSEVIER SCIENCE INC. 1997: 67-73

    Abstract

    This study aimed to quantify the risk of gastrointestinal cancer following Hodgkin's disease treatment according to age at treatment, type of treatment, and anatomic sites.Cases were identified from the records of 2,441 patients treated for Hodgkin's disease between 1961 and 1994. Follow-up averaged 10.9 years, representing 26,590 person-years of observation. Relative risks (RR) for gastrointestinal cancer incidence and mortality were computed by comparison with expected annualized rates for a general population matched for age, sex, and race.Gastrointestinal cancers developed in 25 patients. The incidence RR was 2.5 [95% confidence interval (CI), 1.5-3.5] and mortality RR was 3.8 (CI, 2.4-4.7). Sites associated with significantly increased risks included the stomach [RR 7.3 (CI, 3.4-13.8)], small intestine [RR 11.6 (CI, 1.9-38.3)], and pancreas [RR 3.5 (CI, 1.1-8.5)]. Risk was significantly elevated after combined modality therapy, RR 3.9 (CI, 2.2-5.6). The risk after radiotherapy alone was 2.0 (CI, 1.0-3.4), not a statistically significant elevation. The RR for gastrointestinal cancer was greatest after treatment at young age and decreased with advancing age. It was significantly elevated within 10 years after treatment [RR 2.0 (CI, 1.1-3.5)] and increased further after 20 years [RR 6.1 (CI, 2.5-12.7)]. Risk assessed by attained age paralleled risk according to age at treatment. Fifteen cases of gastrointestinal cancers arose within the irradiation fields.Patients treated for Hodgkin's disease are at modestly increased risk for secondary gastrointestinal cancer, especially after combined modality therapy and treatment at a young age. Risk was highest more than 20 years after treatment, but was significantly elevated within 10 years. Gastrointestinal sites with increased risk included the stomach, pancreas, and small intestine.

    View details for Web of Science ID A1997WJ64600009

    View details for PubMedID 9054878

  • THYROID ABNORMALITIES AFTER THERAPEUTIC EXTERNAL RADIATION Hancock, S. L., McDougall, I. R., Constine, L. S. ELSEVIER SCIENCE INC. 1995: 1165-1170

    Abstract

    The thyroid gland is the largest pure endocrine gland in the body and one of the organs most likely to produce clinically significant abnormalities after therapeutic external radiation. Radiation doses to the thyroid that exceed approximately 26 Gy frequently produce hypothyroidism, which may be clinically overt or subclinical, as manifested by increased serum thyrotropin and normal serum-free thyroxine concentrations. Pituitary or hypothalamic hypothyroidism may arise when the pituitary region receives doses exceeding 50 Gy with conventional, 1.8-2 Gy fractionation. Direct irradiation of the thyroid may increase the risk of Graves' disease or euthyroid Graves' ophthalmopathy. Silent thyroiditis, cystic degeneration, benign adenoma, and thyroid cancer have been observed after therapeutically relevant doses of external radiation. Direct or incidental thyroid irradiation increases the risk for well-differentiated, papillary, and follicular thyroid cancer from 15- to 53-fold. Thyroid cancer risk is highest following radiation at a young age, decreases with increasing age at treatment, and increases with follow-up duration. The potentially prolonged latent period between radiation exposure and the development of thyroid dysfunction, thyroid nodularity, and thyroid cancer means that individuals who have received neck or pituitary irradiation require careful, periodic clinical and laboratory evaluation to avoid excess morbidity.

    View details for Web of Science ID A1995QU29500009

    View details for PubMedID 7713780

  • CONTROL OF PROSTATE-CANCER WITH RADIOTHERAPY - LONG-TERM RESULTS Bagshaw, M. A., Cox, R. S., Hancock, S. L. ELSEVIER SCIENCE INC. 1994: 1781-1785

    Abstract

    The long-term outcome for 1,245 patients with carcinoma of the prostate treated with external beam radiation therapy is presented. The median survival for all patients without evidence of distant metastases but irrespective of T stage of the primary tumor, histopathological grade or lymph node status was 10 years compared to 15 years for an age-matched cohort of California men. The cause specific survival at 15 years was 52%. The data base is subdivided into a series of subsets that demonstrate the impact of T stage, Gleason pattern score and lymph node involvement on long-term outcome. The best results were shown in stages T1 and T2a cases with histopathologically proved negative lymph nodes. Survival at 15 years was 53%, which was essentially identical to the 55% survival rate of an age-matched cohort. The actuarial survival at 15 years for all stages T1 and T2N0M0 cancer patients was 45% compared to 56% for an age-matched cohort.

    View details for Web of Science ID A1994PL68600029

    View details for PubMedID 7933237

  • RADIATION OR SURGERY FOR CARCINOMA OF THE ESOPHAGUS - THE ROLE OF ORGAN-CONSERVING THERAPY Hancock, S. L. KARGER. 1993: 103-117

    View details for Web of Science ID A1993BY26H00008

    View details for PubMedID 8504939

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