Bio

Clinical Focus


  • Lymphoma
  • Hodgkin's Disease - Medical Oncology
  • Hodgkin's Disease
  • Medical Oncology
  • Cancer > Lymphoma
  • Hodgkin's Disease - Hematology

Academic Appointments


Professional Education


  • Fellowship:Memorial Sloan-Kettering Cancer Center (1958) NY
  • Medical Education:Case Western Reserve University School of Dentistry (1953) OH
  • Residency:Peter Bent Brigham Hospital (1961) MA
  • Residency:Peter Bent Brigham Hospital (1957) MA
  • Board Certification: Medical Oncology, American Board of Internal Medicine (1973)
  • Board Certification: Internal Medicine, American Board of Internal Medicine (1961)
  • Internship:University Hospitals of Cleveland (1954) OH

Research & Scholarship

Current Research and Scholarly Interests


Clinical Investigations of Hodgkin’s Disease: Current trials are defining (1) the utility of an abbreviated chemotherapy and minimal radiotherapy for favorable, clinically-staged patients with the disease; (2) the development of new dose-intensive chemotherapy programs for unfavorable and advanced disease. In collaboration with radiotherapists and Dr. Sandra Horning, careful retrospective and prospective studies of fertility, cardiopulmonary and secondary neoplasms are being done.

Clinico-laboratory Studies in the Non-Hodgkin’s Lymphomas: A major research interest of Dr. Rosenberg is the clinical, pathological and molecular basis of diagnosis, evolution, treatment and understanding of the non-Hodgkin’s lymphomas. This research is performed by a large interdisciplinary group of investigators which Dr. Ronald Levy directs.

Teaching

2013-14 Courses


Publications

Journal Articles


  • Improvements in observed and relative survival in follicular grade 1-2 lymphoma during 4 decades: the Stanford University experience. Blood Tan, D., Horning, S. J., Hoppe, R. T., Levy, R., Rosenberg, S. A., Sigal, B. M., Warnke, R. A., Natkunam, Y., Han, S. S., Yuen, A., Plevritis, S. K., Advani, R. H. 2013; 122 (6): 981-987

    Abstract

    Recent studies report an improvement in overall survival (OS) of patients with follicular lymphoma (FL). Previously untreated patients with grade 1-2 FL referred from 1960-2003 and treated at Stanford were identified. Four eras were considered: era 1, pre-anthracycline (1960-1975, n=180); era 2, anthracycline (1976-1986, n=426), era 3, aggressive chemotherapy/purine analogs (1987-1996, n=471) and era 4, rituximab (1997-2003, n=257). Clinical characteristics, patterns of care and survival outcomes were assessed. Observed OS was compared with the expected OS calculated from Berkeley Mortality Database life tables derived from population matched by gender and age at time of diagnosis. The median OS was 13.6 years. Age, gender and stage did not differ across the eras. Although primary treatment varied, event free survival after the first treatment did not differ between eras (p=0.17). Median OS improved from approximately 11 years in eras 1 and 2 to 18.4 years in era 3 and has not yet been reached for era 4 (p<0.001) with no suggestion of a plateau in any era. These improvements in OS exceeded improvements in survival in the general population during the same time period. Several factors, including better supportive care and effective therapies for relapsed disease, are likely responsible for this improvement.

    View details for DOI 10.1182/blood-2013-03-491514

    View details for PubMedID 23777769

  • Efficacy of abbreviated Stanford V chemotherapy and involved-field radiotherapy in early-stage Hodgkin lymphoma: mature results of the G4 trial ANNALS OF ONCOLOGY Advani, R. H., Hoppe, R. T., Baer, D., Mason, J., Warnke, R., Allen, J., Daadi, S., Rosenberg, S. A., Horning, S. J. 2013; 24 (4): 1044-1048

    Abstract

    To assess the efficacy of an abbreviated Stanford V regimen in patients with early-stage Hodgkin lymphoma (HL). PATIENTS AND METHODS PATIENTS: with untreated nonbulky stage I-IIA supradiaphragmatic HL were eligible for the G4 study. Stanford V chemotherapy was administered for 8 weeks followed by radiation therapy (RT) 30 Gy to involved fields (IF). Freedom from progression (FFP), disease-specific survival (DSS) and overall survival (OS) were estimated.All 87 enrolled patients completed the abbreviated regimen. At a median follow-up of 10 years, FFP, DSS and OS are 94%, 99% and 94%, respectively. Therapy was well tolerated with no treatment-related deaths.Mature results of the abbreviated Stanford V regimen in nonbulky early-stage HL are excellent and comparable to the results from other contemporary therapies.

    View details for DOI 10.1093/annonc/mds542

    View details for Web of Science ID 000316701300027

    View details for PubMedID 23136225

  • Risk of Therapy-Related Secondary Leukemia in Hodgkin Lymphoma: The Stanford University Experience Over Three Generations of Clinical Trials JOURNAL OF CLINICAL ONCOLOGY Koontz, M. Z., Horning, S. J., Balise, R., Greenberg, P. L., Rosenberg, S. A., Hoppe, R. T., Advani, R. H. 2013; 31 (5): 592-598

    Abstract

    To assess therapy-related acute myeloid leukemia/myelodysplastic syndrome (t-AML/MDS) risk in patients treated for Hodgkin lymphoma (HL) on successive generations of Stanford clinical trials.Patients with HL treated at Stanford with at least 5 years of follow-up after completing therapy were identified from our database. Records were reviewed for outcome and development of t-AML/MDS.Seven hundred fifty-four patients treated from 1974 to 2003 were identified. Therapy varied across studies. Radiotherapy evolved from extended fields (S and C studies) to involved fields (G studies). Primary chemotherapy was mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) or procarbazine, mechlorethamine, and vinblastine (PAVe) in S studies; MOPP, PAVe, vinblastine, bleomycin, and methotrexate (VBM), or doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) in C studies; and VbM (reduced dose of bleomycin compared with VBM) or mechlorethamine, doxorubicin, vinblastine, vincristine, bleomycin, etoposide, and prednisone (Stanford V) in G studies. Cumulative exposure to alkylating agent (AA) was notably lower in the G studies compared with the S and C studies, with a 75% to 83% lower dose of nitrogen mustard in addition to omission of procarbazine and melphalan. Twenty-four (3.2%) of 754 patients developed t-AML/MDS, 15 after primary chemotherapy and nine after salvage chemotherapy for relapsed HL. The incidence of t-AML/MDS was significantly lower in the G studies (0.3%) compared with the S (5.7%) or C (5.2%) studies (P < .001). Additionally, in the G studies, no t-AML/MDS was noted after primary therapy, and the only patient who developed t-AML/MDS did so after second-line therapy.Our data demonstrate the relationship between the cumulative AA dose and t-AML/MDS. Limiting the dose of AA and decreased need for secondary treatments have significantly reduced the incidence of t-AML/MDS, which was extremely rare in the G studies (Stanford V era).

    View details for DOI 10.1200/JCO.2012.44.5791

    View details for Web of Science ID 000314820400017

    View details for PubMedID 23295809

  • STAGE I-IIIA NON-BULKY HODGKIN'S LYMPHOMA. IS FURTHER DISTINCTION BASED ON PROGNOSTIC FACTORS USEFUL? THE STANFORD EXPERIENCE INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS Advani, R. H., Hoppe, R. T., Maeda, L. S., Baer, D. M., Mason, J., Rosenberg, S. A., Horning, S. J. 2011; 81 (5): 1374-1379

    Abstract

    In the United States, early-stage Hodgkin's lymphoma (HL) is defined as asymptomatic stage I/II non-bulky disease. European groups stratify patients to more intense treatment by considering additional unfavorable factors, such as age, number of nodal sites, sedimentation rate, extranodal disease, and elements of the international prognostic score for advanced HL. We sought to determine the prognostic significance of these factors in patients with early-stage disease treated at Stanford University Medical Center.This study was a retrospective analysis of 101 patients treated with abbreviated Stanford V chemotherapy (8 weeks) and 30-Gy (n=84 patients) or 20-Gy (n=17 patients) radiotherapy to involved sites. Outcomes were assessed after applying European risk factors.At a median follow-up of 8.5 years, freedom from progression (FFP) and overall survival (OS) rates were 94% and 97%, respectively. From 33% to 60% of our patients were unfavorable per European criteria (i.e., German Hodgkin Study Group [GHSG], n=55%; European Organization for Research and Treatment of Cancer, n=33%; and Groupe d'Etudes des Lymphomes de l'Adulte, n=61%). Differences in FFP rates between favorable and unfavorable patients were significant only for GHSG criteria (p=0.02) with there were no differences in OS rates for any criteria. Five of 6 patients who relapsed were successfully salvaged.The majority of our patients deemed unfavorable had an excellent outcome despite undergoing a significantly abbreviated regimen. Application of factors used by the GHSG defined a less favorable subset for FFP but with no impact on OS. As therapy for early-stage disease moves to further reductions in therapy, these factors take on added importance in the interpretation of current trial results and design of future studies.

    View details for DOI 10.1016/j.ijrobp.2010.07.041

    View details for Web of Science ID 000297602400024

    View details for PubMedID 20934280

  • Rare presentation of classical Hodgkin lymphoma with a clonal T-cell receptor gene rearrangement in the tissue LEUKEMIA & LYMPHOMA Nguyen, T. T., Warnke, R. A., Seo, K., Rosenberg, S. A., Arber, D. A. 2010; 51 (7): 1356-1359

    View details for DOI 10.3109/10428194.2010.486094

    View details for Web of Science ID 000279485700026

    View details for PubMedID 20496992

  • Dynamic CD8 T-Cell Responses to Tumor-Associated Epstein-Barr Virus Antigens in Patients With Epstein-Barr Virus-Negative Hodgkin's Disease ONCOLOGY RESEARCH Kohrt, H., Johannsen, A., Hoppe, R., Horning, S. J., Rosenberg, S. A., Advani, R., Lee, P. P. 2009; 18 (5-6): 287-292

    Abstract

    In almost half of patients diagnosed with Hodgkin's disease (HD), the malignant Reed-Sternberg (RS) cells express Epstein-Barr virus (EBV) antigens. Multiple translational efforts are actively investigating antitumor immune strategies by stimulating cytotoxic T lymphocytes (CTL) against tumor-associated EBV antigens. It has previously been believed that this therapeutic strategy and presence of EBV-specific CTLs are limited to EBV-positive HD. In an effort to explore the EBV-specific immune response, here we characterize EBV-specific CTL responses to lytic and latent EBV antigens in 12 consecutive EBV carriers with EBV-negative HD. Compared to healthy donors, we detected weak, baseline EBV-specific responses to both lytic and latent antigens by IFN-gamma ELISPOT in patients with EBV-negative HD at diagnosis. Chemoradiotherapy was associated temporally with a decrease EBV-specific responses. At final follow-up (24 months), recovery of EBV-specific CTL responses was observed with robustness of lytic-specific response equivalent to healthy controls. We confirm evidence of EBV-specific CTLs in patients with EBV-negative HD and provide the first report of dynamic variance in this population during treatment. Our observation challenges prior belief that patients with HD remain immunodeficient following therapy and argues that the clinical significance of the EBV-specific immune response in EBV-negative HD should be further investigated.

    View details for DOI 10.3727/096504009X12596189659169

    View details for Web of Science ID 000274459900010

    View details for PubMedID 20225766

  • Lymphography: A Great Advance, Abandoned JOURNAL OF CLINICAL ONCOLOGY Rosenberg, S. A. 2008; 26 (35): 5662-5663

    View details for DOI 10.1200/JCO.2008.20.6946

    View details for Web of Science ID 000261528200001

    View details for PubMedID 19001339

  • Follicular lymphoma revisited JOURNAL OF CLINICAL ONCOLOGY Rosenberg, S. A. 2008; 26 (4): 515-516

    View details for DOI 10.1200/JCO.2007.13.8131

    View details for Web of Science ID 000254177400001

    View details for PubMedID 18235110

  • Impact of positive positron emission tomography on prediction of freedom from progression after Stanford V chemotherapy in Hodgkin's disease JOURNAL OF CLINICAL ONCOLOGY Advani, R., Maeda, L., Lavori, P., Quon, A., Hoppe, R., Breslin, S., Rosenberg, S. A., Horning, S. J. 2007; 25 (25): 3902-3907

    Abstract

    To correlate [(18)F]fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) status after chemotherapy, but before radiation, with outcome in patients treated with the Stanford V regimen.We analyzed retrospectively 81 patients with Hodgkin's disease who had serial [(18)F]FDG-PET scans performed at baseline and again at the completion of Stanford V chemotherapy, before planned radiotherapy. Patients with favorable stage I/II (nonbulky mediastinal disease) and those with bulky mediastinal disease or stage III/IV were scanned after 8 and 12 weeks of chemotherapy, respectively. Radiotherapy fields were determined before starting chemotherapy based on baseline computed tomography scans.After chemotherapy, six of 81 patients had residual [(18)F]FDG-PET-positive sites, all in sites for which radiotherapy was planned. Four of the six patients with positive [(18)F]FDG-PET scans after chemotherapy experienced relapse compared with just three of 75 patients with negative [(18)F]FDG-PET scans. At a median follow-up of 4 years, the freedom from progression (FFP) was 96% in postchemotherapy [(18)F]FDG-PET-negative patients versus 33% in [(18)F]FDG-PET-positive patients (P < .0003). In a bivariate Cox model, [(18)F]FDG-PET positivity after chemotherapy remained a highly significant predictor of progression-free survival even after controlling for bulky disease and International Prognostic Score more than 2.These data indicate that PET status after chemotherapy is strongly predictive of FFP with the Stanford V regimen despite the use of consolidative radiotherapy. These results have implications for the design of clinical trials adapted to functional imaging.

    View details for DOI 10.1200/JCO.2007.11.9867

    View details for Web of Science ID 000249416000019

    View details for PubMedID 17664458

  • Splenic diffuse large B-cell lymphoma in a patient with type 1 Gaucher disease: diagnostic and therapeutic challenges ANNALS OF HEMATOLOGY Brody, J. D., Advani, R., Shin, L. K., Bingham, D. B., Rosenberg, S. A. 2006; 85 (11): 817-820

    View details for DOI 10.1007/s00277-006-0176-3

    View details for Web of Science ID 000240520100011

    View details for PubMedID 16937096

  • Stage I and II follicular non-Hodgkin's lymphoma: Long-term follow-up of no initial therapy JOURNAL OF CLINICAL ONCOLOGY Advani, R., Rosenberg, S. A., Horning, S. J. 2004; 22 (8): 1454-1459

    Abstract

    To analyze the outcome of no initial therapy in stage I and II follicular small-cleaved (FSC) and follicular mixed (FM) non-Hodgkin's lymphoma (NHL) on overall survival, time to treatment, incidence and course of transformation, and cause of death.This was a retrospective analysis. Criteria for selection were patients with stage I and IIA FSC and FM (grades 1 and 2) NHL with therapy deferred for at least 3 months after diagnosis and a minimum follow-up of 1 year.Forty-three patients were identified (11 stage I, 32 stage II), with a median age of 58 years. Reasons for no initial therapy included: physician choice (n = 20), large abdominal radiation field required (n = 10), advanced age (n = 7), concern for xerostomia (n = 4), or patient refusal (n = 2). At a median follow-up of 86 months, 27 patients (63%) had not been treated. The median time to treatment in the remaining 16 patients was 22 months. Four of 16 patients transformed to a higher-grade lymphoma. Nine patients died-six due to progressive lymphoma. Estimated survivals at 5, 10, and 20 years were 97%, 85%, and 22%, respectively.In selected stage I and II follicular NHL patients, deferred therapy is an acceptable approach, as more than half of our patients remained untreated at a median of 6 or more years, and survival was comparable to that seen in reports with immediate treatment.

    View details for DOI 10.1200/JCO.2004.10.086

    View details for Web of Science ID 000220912200016

    View details for PubMedID 15024027

  • Stanford V and radiotherapy for locally extensive and advanced Hodgkin's disease: Mature results of a prospective clinical trial JOURNAL OF CLINICAL ONCOLOGY Horning, S. J., Hoppe, R. T., Breslin, S., Bartlett, N. L., Brown, B. W., Rosenberg, S. A. 2002; 20 (3): 630-637

    Abstract

    To provide more mature data on the efficacy and complications of a brief, dose-intense chemotherapy regimen plus radiation therapy (RT) to bulky disease sites for locally extensive and advanced-stage Hodgkin's disease.One hundred forty-two patients with stage III or IV or locally extensive mediastinal stage I or II Hodgkin's disease received Stanford V chemotherapy for 12 weeks followed by 36-Gy RT to initial sites of bulky (> or =5 cm) or macroscopic splenic disease. Freedom from progression (FFP), overall survival (OS), and freedom from second relapse (FF2R) were determined using life-table estimates. Outcomes were analyzed according to the international prognostic score. Late effects of treatment were recorded in follow-up.With a median follow-up of 5.4 years, the 5-year FFP was 89% and the OS was 96%. No patient progressed during treatment, and there were no treatment-related deaths. FFP was significantly superior among patients with a prognostic score of 0 to 2 compared with those with a score of 3 and higher (94% v 75%, P <.0001). No secondary leukemia was observed. To date, there have been 42 pregnancies after treatment. Among 16 patients who relapsed, the FF2R was 69% at 5 years.These data confirm our preliminary report that Stanford V chemotherapy with RT to bulky disease sites is highly effective in locally extensive and advanced Hodgkin's disease. It is most important to compare this approach with standard doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy in the ongoing intergroup trial (E2496) to determine whether Stanford V with or without RT represents a therapeutic advance.

    View details for Web of Science ID 000173669400007

    View details for PubMedID 11821442

  • High-dose therapy and autologous bone marrow transplantation for follicular lymphoma in first complete or partial remission: results of a phase II clinical trial BLOOD Horning, S. J., Negrin, R. S., Hoppe, R. T., Rosenberg, S. A., Chao, N. J., Long, G. D., Brown, B. W., Blume, K. G. 2001; 97 (2): 404-409

    Abstract

    Advanced stage follicular small cleaved and mixed cell lymphoma is characterized by relapse from remission and survival ranging from 6 to 12 years. Because young patients have the greatest compromise in longevity, the efficacy and toxicity of high-dose radiochemotherapy and bone marrow transplantation after conventional chemotherapy was evaluated in a prospective phase II clinical trial. Thirty-seven patients in a minimal disease state after conventional chemotherapy received fractionated total body irradiation and high-dose etoposide and cyclophosphamide, followed by purged autologous bone marrow. A reference sample of 188 patients of similar age, stage, and histology managed at this institution before 1988 was identified for comparison of patient characteristics and outcomes. Compared with reference patients, transplant recipients had a higher tumor burden at diagnosis. With a median follow-up of 6.5 years, the estimated 10-year survival after transplantation was 86%. There was a single lymphoma death yielding a 10-year disease-specific survival of 97%. There were 2 early transplant-related deaths and 2 late acute leukemia deaths. Ten patients relapsed, one with microscopic disease only. High tumor burden at diagnosis and incomplete response to chemotherapy adversely influenced survival in the reference but not in the transplanted patients. The estimated risk of death of 14% and relapse of 30% at 10 years in our transplanted follicular lymphoma patients, the majority of whom had high tumor burdens, compares favorably with our observations in appropriately matched reference patients.

    View details for Web of Science ID 000166388000011

    View details for PubMedID 11154216

  • Treatment of multicentric Castleman's disease complicated by the development of non-Hodgkin's lymphoma with high-dose chemotherapy and autologous peripheral stem-cell support ANNALS OF ONCOLOGY Advani, R., Warnke, R., Rosenberg, S. 1999; 10 (10): 1207-1209

    Abstract

    Castleman's disease or angiofollicular lymph node hyperplasia is a rare entity with a localized/unicentric or a generalized/multicentric presentation. While surgery is curable for most localized presentations, there is limited information regarding the optimal management of the multicentric type. The latter type is associated with a poor prognoses and can be associated with the development of lymphoma and infections.In this report we describe a case of multicentric Castleman's disease who failed steroids and chemotherapy and developed a follicular mixed lymphoma. He was treated with high-dose chemotherapy with autologous stem-cell support and remains disease at four years of follow-up.A long-term durable remission may be possible with high dose chemotherapy with stem-cell support. This treatment modality should be considered an option in the management of multicentric Castleman's disease.

    View details for Web of Science ID 000083272400014

    View details for PubMedID 10586338

  • 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

  • Comparison between conventional salvage therapy and high-dose therapy with autografting for recurrent or refractory Hodgkin's disease BLOOD Yuen, A. R., Rosenberg, S. A., Hoppe, R. T., HALPERN, J. D., Horning, S. J. 1997; 89 (3): 814-822

    Abstract

    Sixty patients with Hodgkin's disease, refractory to or at first recurrence after chemotherapy, received cytoreductive therapy followed by high-dose etoposide, cyclophosphamide and either total body irradiation or carmustine and autografting (median follow-up, 3.6 years; range, 1.1 to 7.5 years). A matched conventional salvage group of 103 patients was selected from patients treated at Stanford University Medical Center between January 1976 and January 1989 (median follow-up, 10.3 years; range, 3.0 to 15.7 years). Overall survival (OS), event-free survival (EFS), and freedom from progression (FFP) at 4 years follow-up favored patients who received high-dose therapy compared with conventional salvage treatment (OS: 54% v 47%, P = .25; EFS: 53% v 27%, P < .01; FFP: 62% v 32%, P < .01). In Cox regression analysis, response to cytoreductive or salvage therapy and B symptoms at relapse were the most important predictors of OS. The use of high-dose therapy at relapse, a longer duration of remission, and favorable response to cytoreductive or salvage therapy were most predictive of superior FFP and EFS. These data from a single institution comparing conventional and high-dose therapy in matched patients demonstrate an advantage for high-dose therapy and autografting in the sustained control of Hodgkin's disease. As with primary therapy, it is difficult to demonstrate a statistically significant survival advantage, despite an apparently superior cure rate. However, patients failing induction therapy or relapsing within 1 year benefited significantly from high-dose therapy by all outcome measures (OS, EFS, FFP). As the transplant-related mortality rates decline in Hodgkin's disease, it is predicted that cure rates and late effects will become ultimate determinants of the success of high-dose therapy and autografting.

    View details for Web of Science ID A1997WG07300009

    View details for PubMedID 9028312

  • The management of Hodgkin's disease: Half a century of change - The Kaplan Memorial Lecture ANNALS OF ONCOLOGY Rosenberg, S. A. 1996; 7 (6): 555-560

    Abstract

    The results of treating more than 2600 patients with Hodgkin's disease at Stanford over a 35-year period are summarized. It is now a reality that Hodgkin's disease can be cured with initial treatment programs in virtually all patients, except the elderly. Histologic factors, staging methods, and prognostic groups are becoming less and less relevant. The current protocols used at Stanford and elsewhere will be reviewed to emphasize that combined modality is really the key to improving the cure rate and minimizing late complications.

    View details for Web of Science ID A1996VG53400009

    View details for PubMedID 8879367

  • 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

  • CLASSIFICATION OF LYMPHOID NEOPLASMS BLOOD Rosenberg, S. A. 1994; 84 (5): 1359-1360

    View details for Web of Science ID A1994PE38700001

    View details for PubMedID 8068935

  • Modern combined modality management of Hodgkin's disease. Current opinion in oncology Rosenberg, S. A. 1994; 6 (5): 470-472

    Abstract

    The combination of chemotherapy and irradiation in the management of patients with Hodgkin's disease is being reported with increased frequency. In some situations, higher cure rates have been achieved with combined modality. In other situations, a reduction or modification of one or both modalities has reduced the acute toxicity (and later morbidity) of successful therapy.

    View details for PubMedID 7827149

  • The treatment of Hodgkin's disease. Annals of oncology Rosenberg, S. A. 1994; 5: 17-21

    View details for PubMedID 8204516

  • THE STANFORD EXPERIENCE WITH COMBINED PROCARBAZINE, ALKERAN AND VINBLASTINE (PAVE) AND RADIOTHERAPY FOR LOCALLY EXTENSIVE AND ADVANCED STAGE HODGKINS-DISEASE ANNALS OF ONCOLOGY Horning, S. J., Ang, P. T., Hoppe, R. T., Rosenberg, S. A. 1992; 3 (9): 747-754

    Abstract

    This report describes the efficacy and toxicity of PAVe (procarbazine, Alkeran, vinblastine) and irradiation (RT) in the management of 159 patients with locally extensive or advanced stage Hodgkin's disease (HD) at Stanford University. Patients received six courses of chemotherapy alternating with RT. The extent of RT and the schedule of treatment varied according to the stage of disease. About 2/3 of patients received PAVe/RT in the setting of prospective, randomized clinical trials. The rate of complete response was 93%. With a median follow-up of seven years (range 2-17), the 15 year actuarial freedom from progression (FFP) is 78% and overall survival is 75%. Ten-year FFP by stage is: 80% for locally extensive stage II, 90% for stage IIIA and 70% for stage IIIB. Excellent and equal results were attained with PAVe/RT vs. MOP(P) (mustard, Oncovin, procarbazine with or without prednisone)/RT in the randomized combined modality studies. Progression or recurrence was documented in 30 patients and was more common in irradiated sites. PAVe was well tolerated acutely. There were no treatment related fatalities. Twenty-three (14%) patients were admitted to the hospital for neutropenic fever. Five second malignancies have occurred after PAVe/RT only: one myelodysplastic syndrome, one acute myelogenous leukemia, one non-Hodgkin's lymphoma and two solid tumors including a case of non-small cell lung cancer and an in situ carcinoma of the cervix. Three patients died from myocardial infarction several years after the completion of treatment. These mature data show that PAVe/RT is effective and well-tolerated therapy for locally extensive stage II and IIIA/B HD.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1992JW88200021

    View details for PubMedID 1450064

  • REDUCING THE TOXICITY OF THE COMBINED MODALITY THERAPY OF FAVORABLE STAGE HODGKINS-DISEASE EUROPEAN JOURNAL OF CANCER Rosenberg, S. A. 1992; 28A (8-9): 1379-1380

    View details for Web of Science ID A1992JC98100023

    View details for PubMedID 1515253

  • CEPP(B) - AN EFFECTIVE AND WELL-TOLERATED REGIMEN IN POOR-RISK, AGGRESSIVE NON-HODGKINS-LYMPHOMA BLOOD Chao, N. J., Rosenberg, S. A., Horning, S. J. 1990; 76 (7): 1293-1298

    Abstract

    Eighty-three patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with CEPP(B) (cyclophosphamide, etoposide [VP-16], procarbazine, and prednisone with or without bleomycin) chemotherapy at Stanford University Medical Center (Stanford, CA) from January 1982 through June 1989. Sixty-nine received CEPP(B) as second-line or subsequent therapy after relapse from previous combination chemotherapy, and 14 patients received CEPP(B) as first-line therapy. Of 75 patients evaluable for response, 30 patients (40%) achieved a complete response (CR) and 24 patients (32%) achieved a partial response (PR), providing an overall response rate of 72%. Complete responses were recorded on 21 of 61 (34%) patients with recurrent disease and 9 of the 14 patients who received CEPP(B) as first line therapy (64%). Myelosuppression was the major side effect of treatment, resulting in eight neutropenic-febrile episodes from a total of 253 courses. A single fatal toxic event occurred on a patient who developed adult respiratory distress syndrome. Overall, CEPP(B) was well-tolerated and proved to be effective palliative therapy for patients with non-Hodgkin's lymphoma after relapse. As such, CEPP(B) may be considered for cytoreduction before ablative therapy and bone marrow transplantation. CEPP(B) may also be considered for initial therapy in selected patients who cannot tolerate doxorubicin-containing regimens.

    View details for Web of Science ID A1990EB07800005

    View details for PubMedID 2207307

  • HODGKINS-DISEASE - CHALLENGES FOR THE FUTURE CANCER RESEARCH Rosenberg, S. A. 1989; 49 (4): 767-769

    Abstract

    Clinical investigators of Hodgkin's disease of the recent past have reason to be proud. Tens of thousands of individuals, many of them young, fertile, and productive, have been cured of their life-threatening disease. There are few better examples of the success and rewards of clinical oncology than in the control of Hodgkin's disease by improved diagnostic methods and the appropriate use of radiation and chemotherapy. Yet the clinical investigator of today cannot be satisfied with these successes. The treatment required for high cure rates remains empirical, difficult, and costly. The goal must be to prevent or reverse this fascinating disease, utilizing specific therapy designed from a knowledge of the cause and pathogenesis of the disease. There are sufficient biological clues and methodologies to predict that this will be possible, and in the decade of the 1990s!

    View details for Web of Science ID A1989T082400001

    View details for PubMedID 2643461

  • PROGNOSTIC INDICATORS OF LAPAROTOMY FINDINGS IN CLINICAL STAGE-I-II SUPRADIAPHRAGMATIC HODGKINS-DISEASE JOURNAL OF CLINICAL ONCOLOGY LEIBENHAUT, M. H., Hoppe, R. T., Efron, B., Halpern, J., Nelsen, T., Rosenberg, S. A. 1989; 7 (1): 81-91

    Abstract

    Between July 1968 and July 1986, 915 patients with clinical stage (CS) I and II Hodgkin's disease limited to sites above the diaphragm underwent laparotomy and splenectomy at Stanford University. Fifteen percent were CS I, of whom 76% had cervical/supraclavicular disease, 13% axillary disease, and 9% mediastinal presentations. CS I patients were more likely to be male, were significantly older, and were significantly less likely to have nodular sclerosis (NS) histology than CS II patients. Twenty percent of CS I patients and 30% of CS II patients were pathologically upstaged. No CS I patients were upstaged to pathological stage (PS) IV. Univariate and multivariate analyses of presenting clinical characteristics were performed to predict staging laparotomy findings. CS I women, CS I patients with mediastinal-only disease, and CS I men with either lymphocyte predominance or interfollicular histologies were at low risk for having disease below the diaphragm (5%) or requiring chemotherapy (0%). CS II women who were less than 27 years old and had only two or three sites of disease were also at low risk for upstaging (9%) or requiring chemotherapy (2%). Mixed cellularity histology and male gender were associated with increased risk for subdiaphragmatic disease and require laparotomy; the presence of systemic symptoms was not correlated with laparotomy findings. These results confirm the importance of performing staging laparotomy for the majority of patients who present with supradiaphragmatic Hodgkin's disease if treatment programs are based on the presence and extent of subdiaphragmatic disease. Selected subgroups are at low risk for subdiaphragmatic disease and might be spared laparotomy if they are treated with mantle, paraaortic, and splenic irradiation.

    View details for Web of Science ID A1989R711000012

    View details for PubMedID 2909669

  • 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

  • EXPLORATORY LAPAROTOMY AND SPLENECTOMY FOR HODGKINS-DISEASE - A COMMENTARY JOURNAL OF CLINICAL ONCOLOGY Rosenberg, S. A. 1988; 6 (4): 574-575

    View details for Web of Science ID A1988N007300002

    View details for PubMedID 3357003

Conference Proceedings


  • Brief chemotherapy (Stanford V) and adjuvant radiotherapy for bulky or advanced Hodgkin's disease: An update Horning, S. J., Rosenberg, S. A., Hoppe, R. T. KLUWER ACADEMIC PUBL. 1996: 105-108

    Abstract

    From May 1989 to August 1995, 94 previously untreated patients with Hodgkin's disease stage II with bulky mediastinal involvement (n = 28) or stage III or IV (n = 66) received an abbreviated chemotherapy regimen, Stanford V, +/-radiotherapy (RT). Chemotherapy was given weekly for 12 weeks followed by consolidative RT to sites of initial bulky disease. With a median follow-up of 3 years, the actuarial 6-year survival is 93% and the freedom from progression is 89%. There have been no relapses or deaths among the 28 patients with stage II bulky mediastinal disease. Eight relapses and three deaths have occurred in the group of 66 patients with stage III-IV disease. The abbreviated chemotherapy regimen, Stanford V, in combination with RT is well tolerated and highly effective therapy for bulky, limited stage and advanced stage HD. Lower cumulative exposure to alkylating agents, doxorubicin, bleomycin and limited use of radiation is expected to improved the prospects for fertility and decrease the risks for second neoplasms and late cardiopulmonary toxicity.

    View details for Web of Science ID A1996UZ46200020

    View details for PubMedID 8836420

  • THE CONTINUING CHALLENGE OF HODGKINS-DISEASE Rosenberg, S. A. KLUWER ACADEMIC PUBL. 1991: 29-31

    Abstract

    Patients with Hodgkin's disease, treated at most major medical centers, enjoy a cure rate on the average of approximately 75 percent. An additional 5 or 10% will not die of Hodgkin's disease, because of the success of secondary treatments or because their deaths result from other related or unrelated causes. There are sub-groups of patients who fare better or worse than this average, depending on prognostic factors such as age, stage, bulk, or site of disease and on the primary management program. Substantial improvements in these curability and survival statistics will be difficult to achieve and demonstrate. The major efforts of clinical investigators of Hodgkin's disease in 1990 are to identify and reduce the serious long-term morbidities of treatment programs and to assure that the excellent outcome results achieved at major centers can be accomplished more widely throughout the world. The emerging challenge for investigators of Hodgkin's disease in the next decade is not only to refine treatment methods but to gain a better understanding of the nature, etiology, and pathogenesis of the disease. There are very important data and observations that suggest that Hodgkin's disease is not a single disease entity, based on epidemiologic, histologic, and immunologic characteristics. Despite the heterogeneity of the disease, familial clustering and HLA correlations give strong evidence that there is a genetic basis for at least a component of the pathogenesis. The new tools and concepts of the molecular geneticist combined with the recognition of more homogeneous disease subgroups give great promise that the genetic basis of Hodgkin's disease will soon be understood.(ABSTRACT TRUNCATED AT 250 WORDS)

    View details for Web of Science ID A1991FB41200004

    View details for PubMedID 2049318

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