Emeritus Faculty, Acad Council, Radiation Oncology - Radiation Therapy
Member, Stanford Cancer Institute
Gynecologic malignancies; Rectal/and cancer; Breast Cancer; Hodgkin's disease; Hyperthermia; intraoperative radiation therapy; High dose rate radiation therapy; Predictive assays; Patterns of tumor spread; Health care finance.
This randomized phase III trial is studying cisplatin, radiation therapy, and tirapazamine to see how well they work compared to cisplatin and radiation therapy in treating patients with cervical cancer. Drugs used in chemotherapy, such as cisplatin and tirapazamine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells. Internal radiation uses radioactive material placed directly into or near a tumor to kill tumor cells. Cisplatin and tirapazamine may make tumor cells more sensitive to radiation therapy. It is not yet known whether giving cisplatin together with radiation therapy is more effective with or without tirapazamine in treating cervical cancer.
Stanford is currently not accepting patients for this trial. For more information, please contact Maureen Sutton, (650) 725 - 9167.
A simplified model for tumorigenesis, locoregional growth, and metastases is proposed for carcinoma of the cervix. With the use of this model, four potential areas for future directions for radiobiologic-clinical research are identified. The first area concerns the influence of human papillomavirus infection and p53 mutations on tumor biology, with particular reference to radiosensitivity and metastatic potential. Research in this area should be most fruitful. The second area focuses on the influence of hypoxia on clinical outcome in carcinoma of the cervix. The use of selective hypoxic cell toxins (e.g., tirapazamine) for phase II testing in hypoxic tumors is recommended. The third area concerns the development and clinical confirmation of assays for the prediction of intrinsic tumor radiosensitivity (e.g., surviving fraction after 2 Gy) and normal tissue radiosensitivity. The need exists for more rapid assays so that their results can be available prior to institution of therapy. The influence of the intrinsic radiosensitivity of normal tissues (especially in patients who are heterozygotes for ataxia-telangiectasia and patients with autoimmune disease) may permit identification of those at increased risk for complications so that alternative, less toxic treatment can be allocated. The fourth area for additional study concerns the influence of both intrinsic (c-myc amplification, matrix metalloproteinase levels) and extrinsic factors (fever, immunosuppression) on the development of distant metastases. Such investigations will permit identification of patients at high risk of developing distant metastases so that adjuvant treatments (e.g., chemotherapy or metalloproteinase inhibitors) can be explored. It is believed that future clarification of our proposed model will lead to other worthwhile areas for therapeutic intervention.
View details for PubMedID 9023843
In this study we evaluate the long-term efficacy and safety of transperineal interstitial implants for advanced pelvic malignancy. A total of 139 patients were treated at Stanford University Medical Center and the Joint Center for Radiation Therapy with transperineal template interstitial brachytherapy for locally advanced or recurrent cancers arising in the pelvic organs. Most patients received whole pelvis external beam irradiation to a median dose of 4200 cGy followed by an implant for a median duration of 48 hr to a median implant dose of 3000 cGy (range 600-6000 cGy). Complete follow-up was obtained for 91% of the patients. Median follow-up for survivors is 57 months (range, 10-173 months). The crude disease-free survival rate was 22% at 5 years. The 5-year crude local tumor control rate was 25%. No dose-response relationship could be demonstrated for tumor control or complications. There were no acute treatment-related deaths. Three late deaths were seen which were directly related to treatment. Major bowel complications requiring surgery were seen in 17% of patients without locally recurrent disease, and fistulas were reported in 4% of these patients. We conclude that template parametrial implant brachytherapy offers a modest chance of cure for women with locally advanced pelvic malignancy. However, this treatment causes significant late morbidity.
View details for Web of Science ID A1995RG49700005
View details for PubMedID 7789885
The optimum management of uterine papillary serous carcinoma (UPSC), a clinically aggressive histologic variant of endometrial adenocarcinoma, is a controversial issue.Ten patients with UPSC were reviewed who received whole abdominopelvic irradiation (WAP) as adjuvant therapy after a staging laparotomy and debulking surgery.Nine patients had clinical Stage I disease; the tumors in eight of them were upstaged based on laparotomy findings. There was greater than a 50% invasion of the myometrium in four of the hysterectomy specimens, and vascular space invasion was noted in seven patients. Peritoneal washings were positive in three of the nine specimens obtained; two others showed atypical cells. Five patients are alive with no evidence of disease at 102-133 months. Four patients are dead, and one patient is alive with disease. All recurrences were observed within 30 months of the initial diagnosis and were more common in the presence of deep myometrial invasion and vascular space involvement. Three of the four patients who died had pleural effusions that did not respond to hormonal and/or chemotherapy. Local irradiation produced long-term control of recurrences in two patients, including one with supraclavicular lymph node metastases who had no evidence of disease 117 months after radiation treatment to the involved nodes.These findings suggest that WAP be considered as an adjuvant therapy in the management of UPSC. The patients with the greatest benefit were those with early disease by surgical staging with or without positive peritoneal cytologic findings. For patients at high risk for pleural effusions and pulmonary metastasis, additional adjuvant therapy, such as innovative chemotherapy or low-dose lung irradiation, needs to be considered.
View details for Web of Science ID A1993LD04100029
View details for PubMedID 8490835
There is still a concern that the use of HDR brachytherapy might result in an increase of late tissue damage. This restrospective study evaluates the incidence and severity of late complications in patients with carcinoma of the cervix who underwent combined external beam radiation (EBR) and Ir-192 HDR brachytherapy and attempts to identify pretreatment and treatment parameters correlating with late complications.Between 1985 and 1992, 161 patients with carcinoma of the cervix (FIGO stages IB-IVB) received EBR to the pelvis (ave, max. dose 48.8 Gy) followed by 1-6 Ir-192 HDR placements (median 2). Doses to point A ranged from 8.5 to 38.7 Gy (median 17 Gy). Parameters examined included age, diabetes, obesity, history of inflammatory bowel disease or diverticulitis, prior surgery, hemoglobin level, FIGO stage, EBR dose, technique and daily dose fraction, number of HDR treatments and total dose to point A, maximum doses to bladder and rectum delivered by brachytherapy and cumulative dose to point A. Median follow-up for all patients was 37 months. Complications were rated using an in-house scoring system and according to the French-Italian Glossary (FIG).Actuarial 5-year survival was 93%, 57%, 46%, and 0% for stages IB, II, IIIB, and IV, respectively. Of 161 patients, 11% developed moderate and 3.7% severe sequelae (FIG: 2.5%, 3.7%). Since some patients experienced more than one complication, the overall incidence was 13.6% and 4.9% (FIG: 3.1%, 4.9%) with respective 5-year actuarial rates of 14% and 5% for moderate, and 2% and 8% for severe bowel and genitourinary tract complications (FIG: 3.5%, 0, and 2%, 8%). All severe bowel complications occurred within 1.5 years whereas urinary tract sequelae continued to develop throughout the follow-up period. FIGO stage was associated with a significant increase in late sequelae (P = 0.015). Analysis of the remaining pretreatment and treatment parameters failed to reveal any statistically significant correlation with moderate or severe sequelae.In our series using HDR brachytherapy, complication and survival rates were comparable with other series employing either LDR or HDR procedures. Of all parameters analysed, stage of disease was the only parameter significantly correlated with complications in univariate and multivariate analysis.
View details for Web of Science ID A1997WR94000005
View details for PubMedID 9106923
Recurrence in the prostatic gland remains a significant problem in the management of locally advanced prostatic cancer. Transperineal thermobrachytherapy has been utilized in an attempt to improve local tumor control. The purpose of this study was to quantitate the temperature distributions obtained in carcinoma of the prostate treated with interstitial radiofrequency-induced hyperthermia given in conjunction with 192Ir brachytherapy in a Phase I study.From 1987 until 1992, 36 patients (5 with locally recurrent, 15 with Stage B, and 16 Stage C prostate cancers) were treated with interstitial brachytherapy implants supplemented with radiofrequency-induced hyperthermia. An array of 7-32 stainless steel trocar electrodes (outer diameter = 1.5 mm, interelectrode spacing = 8 mm) were implanted into the prostate gland through a perineal approach utilizing a specially designed template. Each trocar was electrically insulated along the length which traversed surrounding normal tissues. One to three additional plastic catheters were implanted for automated temperature mapping. Thirty-four of these procedures were performed following lymph node sampling. However, the last two removable interstitial hyperthermic prostate implants were done by the transperineal route under ultrasound guidance. A hyperthermia treatment (goal of 43 degrees C for 45 minutes) was given immediately prior to the insertion and immediately following the removal of the 192Ir. A computer-controlled radiofrequency-based generator (freq. 0.5 MHz) implementing electrode multiplexing was used to induce and maintain elevated temperatures.Transient local pain was the most common treatment limiting factor. The average values of the measured minimum, mean, and maximum temperatures were 38.9 degrees C, 41.9 degrees C, and 45.7 degrees C in tumor, and 37.7 degrees C, 39.8 degrees C, and 42.9 degrees C in surrounding normal tissue, respectively. The percentages of mapped temperatures exceeding 41 degrees C, 42 degrees C, and 43 degrees C were 67%, 46%, and 27% in tumor, and 26%, 11%, and 4% in normal surrounding tissue, respectively.From this study we conclude that heterogeneous temperature distributions were induced in the prostate; significant normal tissue protection was realized in part through the selective insulation of sections of each electrode; and interstitial radiofrequency-induced hyperthermia of the prostate is feasible and well tolerated, with further technical developments warranted.
View details for Web of Science ID A1994MP35300020
View details for PubMedID 8270436