From owner-radoncjc@net.bio.net Fri Apr 7 18:33:10 2000 Return-Path: Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 110) id 99ADD17B0E; Fri, 7 Apr 2000 18:33:01 +0100 (BST) Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 1) id 8BA6517AE5; Fri, 7 Apr 2000 18:32:55 +0100 (BST) To: radoncjc@net.bio.net From: Brian Goldsmith Reply-To: radoncjc@net.bio.net Subject: April 2000 Internet Radiation Oncology Journal Club (IROJC) Message-Id: <20000407173255.8BA6517AE5@mercury.hgmp.mrc.ac.uk> Date: Fri, 7 Apr 2000 18:32:55 +0100 (BST) Sender: owner-radoncjc@net.bio.net Precedence: bulk April 2000 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 59th collection of references suggested for attention and discussion by the IROJC's Board of Editors: Sarah Donaldson, M.D. Editor, Pediatric Radiation Oncology Robert Foote, M.D. Editor, Head and Neck / Skin Radiation Oncology Abram Recht, M.D. Editor, Breast Radiation Oncology Rich Hoppe, M.D. Editor, Reticuloendothelial System Radiation Oncology Dan Petereit, M.D. Editor, Gynecological Radiation Oncology Andrew Turrisi, M.D. Editor, Lung and Mediastinum Radiation Oncology Joel Tepper, M.D. Editor, Gastrointestinal and Soft Tissue Sarcoma Radiation Oncology Mack Roach, M.D. Editor, Genitourinary Radiation Oncology Glenn Bauman, M.D. Ph.D. Editor, Central Nervous System Radiation Oncology Rod Withers, M.D., D.Sc. Editor, Radiobiology James Hayman, M.D. Editor, Health Services Research George Chen, Ph.D. Editor, Radiation Biophysics ----------------------------------------------------- You're encouraged to critically review this set of references and respond by posting your comments to the IROJC readership at radoncjc@net.bio.net. Comments should be in compliance with IROJC commentary rules (see below). In the month that follows this posting of references, submitted comments will be delivered to the e-mail boxes of the IROJC readership. ------------------------------------------------------------ ARCHIVED IROJC material is available at http://www.bio.net/hypermail/radoncjc/ ------------------------------------------------------------ Commentary Rules: (1) Please cite the subject category in the header of your e-mail message, e.g., Subject: CNS 4/00. (2) Address the readership at large - not the Editor who suggested the reference. The Editor is under no obligation to respond to questions posed by the IROJC readership. (3) The Editor's selection is not necessarily an endorsement of the authors' conclusions. In fact, articles may be selected for criticism. (4) Comments posted to the Internet are public. Professional wording is prudent. (5) Comment only on journal articles that you have read recently, and please keep comments specific. (6) In order to minimize confusion, limit comments to the current month's list of references. (7) Please sign all comments and questions to the IROJC. By identifying yourself, you promote a more collegial and friendly environment! (8) Address to the Moderator (briandeb@bellatlantic.net) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 4/00 AU: Friedman DL; Himelstein B; Shields CL; Shields JA; Needle M; Miller D; Bunin GR; Meadows AT. TI: Chemoreduction and local ophthalmic therapy for intraocular retinoblastoma. SO: J Clin Oncol 2000 Jan;18(1):12-7. URL: http://www.jco.org/cgi/content/abstract/18/1/12 PDF: http://www.jco.org/cgi/reprint/18/1/12 Abstract: PURPOSE: To study the effectiveness of combined systemic chemotherapy and local ophthalmic therapy for retinoblastoma with the goal of avoiding enucleation and external-beam radiation therapy (EBRT). PATIENTS AND METHODS: This was a prospective, nonrandomized, single-arm clinical trial. Seventy-five eyes were followed in 47 children. Patients were treated with a six-cycle protocol of vincristine, etoposide, and carboplatin. Most (83%) also received ophthalmic treatment (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy) during and/or after the chemotherapy. RESULTS: With a median follow-up of 13 months, event-free survival was 74%, with an event defined as enucleation and/or EBRT. Six children required EBRT in seven eyes (9%); five required enucleation of one eye (7%); five required a combination of EBRT and enucleation in six eyes (8%). Reese-Ellsworth groups 1, 2, and 3 eyes had excellent results, with avoidance of EBRT or enucleation in all 39. Treatment of groups 4 and 5 was less successful, with 33% of six eyes and 53% of 30 eyes, respectively, requiring EBRT and/or enucleation. Toxicities from chemotherapy were mild and included cytopenias (89%), fever and neutropenia (28%), infection (9%), and gastrointestinal symptoms, dehydration, and vincristine neurotoxicity (40%). No patients developed a second malignancy, metastatic disease, renal disease, or ototoxicity. CONCLUSION: In retinoblastoma patients with Reese-Ellsworth eye groups 1, 2, or 3, systemic chemotherapy used with local ophthalmic therapies can eliminate the need for enucleation or EBRT without significant systemic toxicity. More effective therapy is required for Reese-Ellsworth eye groups 4 and 5. Editor's comments: In an attempt to avoid enucleation, and the sequelae of external beam radiation in infants, this study was designed to use chemotherapy with vincristine, etoposide, carboplatin, and local therapy (cryotherapy, laser photocoagulation, thermotherapy, or plaque radiation therapy). The investigators were successful in 74%; however 26% did require external beam radiation or enucleation for control. The success rate was stage dependent, with no failures in the low stage disease group, but unacceptable results in those with Reese-Ellsworth Stage IV and V disease. The authors conclude that their approach is a success in the low stage patients. My concerns about the paper are that the median follow up of 13 mos. is too short to pronounce success. As well the study group is very selected. Of the 59 potential patients, 12 were excluded because their disease was too advanced, physicians felt that enucleation was more appropriate, or the parents refused participation, leaving only 47 patients and 75 eyes in the study group. Unfortunately, it is uncommon for children with retinoblastoma to present with early stage disease; most present with advanced stage disease in which local non-radiotherapy treatment, or surgery less than enucleation is not appropriate. A final point is that there is no radiation oncologist author on this paper, thus there are no details regarding the plaque radiation, which is unfortunate. One could conclude that external beam radiation remains an important treatment for the majority of children with retinoblastoma who present with some degree of useful vision. ****************** Head/Neck/Skin: Foote 4/00 No Reference Selected ****************** GYN: Petereit 4/00 AU: Klee M; Thranov I; Machin D. TI: Life after radiotherapy: the psychological and social effects experienced by women treated for advanced stages of cervical cancer. SO: Gynecol Oncol 2000 Jan;76(1):5-13. Abstract: PURPOSE: The aim of this study was to describe the psychological and social reactions of women with advanced stages of cancer of the cervix during and after radiotherapy. METHODS: A questionnaire about health-related quality of life was used, which consisted of the EORTC QLQ-C30 and additional specific questions. One-hundred eighteen patients filled out the questionnaire at the end of treatment and 1, 3, 6, 12, 18, and 24 months later. The scores from the disease-free patients were compared to those from 236 healthy controls. RESULTS: Many patients experience psychological and social consequences at the end of treatment and 1 to 3 months later. Patients continue to think about their illness and treatment throughout the 24-month study period, but find it increasingly hard to share their worries with others. Their score on overall quality of life never reaches that of the controls. CONCLUSION: Disease-free patients treated for cancer of the cervix with radiotherapy have psychological reactions. The interpretation of the results should take into consideration that the patients change their personal frame of reference over the course of time. Professionals should be aware of patients' needs to talk about their disease long after treatment. Patients should be informed about the risk of psychological reactions. The more information about possible symptoms they receive the better their ability to cope with them should they arise. Copyright 2000 Academic Press. and AU: Klee M; Thranov I; Machin D. TI: The patients' perspective on physical symptoms after radiotherapy for cervical cancer. SO: Gynecol Oncol 2000 Jan;76(1):14-23. Abstract: PURPOSE: The aim of this study was to describe the physical symptoms experienced by patients with advanced stages of cervical cancer during the first 2 years after radiotherapy. METHODS: A questionnaire about health-related quality of life was used. It consisted of the EORTC QLQ-C30 and additional specific questions. The patients were assessed at the end of treatment and 1, 3, 6, 12, 18, and 24 months later. The scores from the 118 patients were compared to those from 236 healthy controls. RESULTS: Most patients had acute physical symptoms at the end of treatment and up to 3 months later. Local symptoms such as frequent voiding and diarrhea may become chronic symptoms. CONCLUSION: Assessment of health-related quality of life includes information about milder side effects that is not usually included in physician scoring of morbidity. Information about possible side effects improves the patient's ability to cope with the symptoms should they occur. Copyright 2000 Academic Press. Editor's comments: Klee et al. recently published two articles in the same issue of Gynecologic Oncology that evaluated women's perceived quality of life after cervical cancer treatment with radiotherapy. As with other tumor sites, most of the oncologic literature focuses on cure and late complication rates. For patients with reasonably high cure rates, i.e. cervical cancer, other issues begin to take the forefront as women are followed for extended periods of time. Klee reports on two of these issues: psychological and social effects, and physical symptoms - both sets of data were generated from patient questionnaires. Most of the physical and emotional distress occurred during the first few months after treatment and decreased over time; however, some of these symptoms persisted and become chronic. The persistence of these symptoms, according to the authors, may negatively impact patient's quality of life. It is proposed that some of these negative treatment-related effects may be circumvented if identified early. A third publication is to follow with will discuss sexuality for the same patient cohort. An editorial by Schover et al. appears in the same issue of Gynecologic Oncology. As residents rotate from one service to the next in radiation oncology training programs, they uncommonly observe acute side effects that persist, or significant late complications in patients whom they initially treat. As our specialty becomes more comprehensive, these important quality of life issues need to be emphasized to not only our residents as they mature, but more importantly, to our patients as they experience the acute and late effects of our treatment. It is only through anticipating some of these adverse reactions that we will be better prepared to hopefully reverse them. ****************** GI / Soft Tissue Sarcoma: Tepper 4/00 AU: Wolmark N; Wieand HS; Hyams DM; Colangelo L; Dimitrov NV; Romond EH; Wexler M; Prager D; Cruz AB Jr; Gordon PH; Petrelli NJ; Deutsch M; Mamounas E; Wickerham DL; Fisher ER; Rockette H; Fisher B. TI: Randomized Trial of Postoperative Adjuvant Chemotherapy With or Without Radiotherapy for Carcinoma of the Rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. SO: J Natl Cancer Inst 2000 Mar 1;92(5):388-396. URL: http://jnci.oupjournals.org/cgi/content/full/92/5/388 PDF: http://jnci.oupjournals.org/cgi/reprint/92/5/388 Abstract: BACKGROUND: The conviction that postoperative radiotherapy and chemotherapy represent an acceptable standard of care for patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the rectum evolved in the absence of data from clinical trials designed to determine whether the addition of radiotherapy results in improved disease-free survival and overall survival. This study was carried out to address this issue. An additional aim was to determine whether leucovorin (LV)-modulated 5-fluorouracil (5-FU) is superior to the combination of 5-FU, semustine, and vincristine (MOF) in men. PATIENTS AND METHODS: Eligible patients (n = 694) with Dukes' B or C carcinoma of the rectum were enrolled in National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol R-02 from September 1987 through December 1992 and were followed. They were randomly assigned to receive either postoperative adjuvant chemotherapy alone (n = 348) or chemotherapy with postoperative radiotherapy (n = 346). All female patients (n = 287) received 5-FU plus LV chemotherapy; male patients received either MOF (n = 207) or 5-FU plus LV (n = 200). Primary analyses were carried out by use of a stratified log-rank statistic; P values are two-sided. RESULTS: The average time on study for surviving patients is 93 months as of September 30, 1998. Postoperative radiotherapy resulted in no beneficial effect on disease-free survival (P = .90) or overall survival (P = .89), regardless of which chemotherapy was utilized, although it reduced the cumulative incidence of locoregional relapse from 13% to 8% at 5-year follow-up (P = .02). Male patients who received 5-FU plus LV demonstrated a statistically significant benefit in disease-free survival at 5 years compared with those who received MOF (55% versus 47%; P = .009) but not in 5-year overall survival (65% versus 62%; P = .17). CONCLUSIONS: The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone. Editor's comments: This is a very important paper for radiation oncologists since it is one of very few recent studies that has randomized patients to +/- radiation therapy for rectal cancer. The relatively recent Swedish trial did such a randomization (without chemotherapy) using a short course of preoperative RT and found a survival advantage to RT. No matter how one looks at the data in the NSABP study, there is no survival advantage to the use of postoperative RT. Does this mean that RT should not be used in this disease? I think the answer to that is no. First of all, there are good data showing a survival advantage to preoperative RT. Secondly, there was an advantage in local control with the addition of RT. What was not studied, and is of great importance, is what was the impact of a local failure on quality of life and how did that compare to the decrement in QOL from receiving RT. There are a number of other issues that need to be considered. The first is that only the first site of relapse was analyzed and this may be a substantial underestimate of recurrence rates. This may have been amplified by the fact that they asked for biopsies of recurrences. Therefore, if a patient had a biopsy positive liver met at the same time as a new pelvic mass, the recurrence may have been scored as distant only. The second issue is the location of the primary. Patients were accepted onto study if the tumor was below the peritoneal reflection, but it is very hard to get this information on some of the patients. If there were many patients with true sigmoid lesions, that would have skewed the results against RT. Third, there was a substantial advantage to RT in recurrences for patients who had an APR. This is entirely as expected since the local recurrence rates are highest in low tumors, and much less in higher lesions. I have no explanation for the advantage seen with RT in the younger patients in contrast to older patients. This study also incorporated a chemotherapy randomization to MOF vs 5-FU/leucovorin. This confuses the issue a bit, but doesn't really effect the RT randomization in a major way. I think that over the next number of years we will need to fine tune the group of patients in whom adjuvant RT is needed in rectal cancer. We will likely not be treating certain subsets of patients who are at relatively low risk for local failure and may be irradiating some patients with molecular or other factors which are found to put them at high risk. It is likely to be related to the operation performed and perhaps to the completeness of the pathologists assessment. My sense is that the general trend in the country is to use more preoperative radiation therapy, although I have no data to support that. Preoperative RT may have superior long term outcome but the studies designed to test that hypothesis have failed because of low accrual. ****************** CNS: Bauman 4/00 AU: Warren KE; Frank JA; Black JL; Hill RS; Duyn JH; Aikin AA; Lewis BK; Adamson PC; Balis FM. TI: Proton Magnetic Resonance Spectroscopic Imaging in Children With Recurrent Primary Brain Tumors. SO: J Clin Oncol 2000 Mar;18(5):1020. URL: http://www.jco.org/cgi/content/abstract/18/5/1020 PDF: http://www.jco.org/cgi/reprint/18/5/1020 Abstract: PURPOSE: Proton magnetic resonance spectroscopic imaging ((1)H-MRSI) is a noninvasive technique for spatial characterization of biochemical markers in tissues. We measured the relative tumor concentrations of these biochemical markers in children with recurrent brain tumors and evaluated their potential prognostic significance. PATIENTS AND METHODS: (1)H-MRSI was performed on 27 children with recurrent primary brain tumors referred to our institution for investigational drug trials. Diagnoses included high-grade glioma (n = 10), brainstem glioma (n = 7), medulloblastoma/peripheral neuroectodermal tumor (n = 6), ependymoma (n = 3), and pineal germinoma (n = 1). (1)H-MRSI was performed on 1.5-T magnetic resonance imagers before treatment. The concentrations of choline (Cho) and N-acetyl-aspartate (NAA) in the tumor and normal brain were quantified using a multislice multivoxel method, and the maximum Cho:NAA ratio was determined for each patient's tumor. RESULTS: The maximum Cho:NAA ratio ranged from 1.1 to 13.2 (median, 4.5); the Cho:NAA ratio in areas of normal-appearing brain tissue was less than 1.0. The maximum Cho:NAA ratio for each histologic subtype varied considerably; approximately equal numbers of patients within each tumor type had maximum Cho:NAA ratios above and below the median. Patients with a maximum Cho:NAA ratio greater than 4.5 had a median survival of 22 weeks, and all 13 patients died by 63 weeks. Patients with a Cho:NAA ratio less than or equal to 4.5 had a projected survival of more than 50% at 63 weeks. The difference was statistically significant (P =.0067, log-rank test). CONCLUSION: The maximum tumor Cho:NAA ratio seems to be predictive of outcome in children with recurrent primary brain tumors and should be evaluated as a prognostic indicator in newly diagnosed childhood brain tumors. Editor's comments: While the use of metabolic imaging has been well documented in helping to distinguish radiation necrosis from recurrent tumor, this small study suggests that it may be of prognostic utility in predicting biologic aggressiveness. Within a small group of children with recurrent primary brain tumors, a higher choline to n-acetyl-aspartate ratio was an adverse prognostic factors. Children with a ratio > median had significantly shorter median survivals than those with lower ratios (22 vs >63 weeks). Small numbers precluded a multivariate analysis that controlled for the effects of tumor histology, age etc but the authors note that these factors were well balanced between the two groups with higher vs lower ratios. They did note considerable overlap of ratios between tumor histology suggesting this technique could not replace histologic diagnosis. The discussion is a nice succinct review of the recent work in MRI spectroscopy. The authors speculate on some biologic underpinnings behind the prognostic import of the Cho:NAA ratio. Clearly, this sort of study needs to be validated in a larger number of patients with more homogeniety with respect to histology and treatment received. However, once validated, one can imagine using this information to direct treatment planning. One may be able to select patients with adverse metabolic imaging for more intensive treatment (dose escalation, combined modality) and those with favourable imaging for less intensive treatment (decrease side effects). One can also imagine tailoring radiation fields to a biologic gradient on MRSI as opposed to edema, contrast enhanced volume etc. ****************** Breast: Recht 4/00 AU: Vrieling C; Collette L; Bartelink E; Borger JH; Brenninkmeyer SJ; Horiot JC; Pierart M; Poortmans PM; Struikmans H; Van der Schueren E; Van Dongen JA; Van Limbergen E; Bartelink H TI: Validation of the methods of cosmetic assessment after breast-conserving therapy in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer. SO: Int J Radiat Oncol Biol Phys 1999 Oct 1;45(3):667-76 Abstract: PURPOSE: To evaluate both qualitative and quantitative scoring methods for the cosmetic result after breast-conserving therapy (BCT), and to compare the usefulness and reliability of these methods. METHODS AND MATERIALS: In EORTC trial 22881/10882, stage I and II breast cancer patients were treated with tumorectomy and axillary dissection. A total of 5318 patients were randomized between no boost and a boost of 16 Gy following whole-breast irradiation of 50 Gy. The cosmetic result was assessed for 731 patients in two ways. A panel scored the qualitative appearance of the breast using photographs taken after surgery and 3 years later. Digitizer measurements of the displacement of the nipple were also made using these photographs in order to calculate the breast retraction assessment (BRA). The cosmetic results after 3-year follow-up were used to analyze the correlation between the panel evaluation and digitizer measurements. RESULTS: For the panel evaluation the intraobserver agreement for the global cosmetic score as measured by the simple Kappa statistic was 0.42, considered moderate agreement. The multiple Kappa statistic for interobserver agreement for the global cosmetic score was 0.28, considered fair agreement. The specific cosmetic items scored by the panel were all significantly related to the global cosmetic score; breast size and shape influenced the global score most. For the digitizer measurements, the standard deviation from the average value of 30.0 mm was 2.3 mm (7.7%) for the intraobserver variability and 2.6 mm (8.7%) for the interobserver variability. The two methods were significantly, though moderately, correlated; some items scored by the panel were only correlated to the digitizer measurements if the tumor was not located in the inferior quadrant of the breast. CONCLUSIONS: The intra- and interobserver variability of the digitizer evaluation of cosmesis was smaller than that of the panel evaluation. However, there are some treatment sequelae, such as disturbing scars and skin changes, that can not be evaluated by BRA measurements. Therefore, the methods of cosmetic evaluation used in a study must be chosen in a way that balances reliability and comprehensiveness. and AU: Vrieling C; Collette L; Fourquet A; Hoogenraad WJ; Horiot JC; Jager JJ; Pierart M; Poortmans PM; Struikmans H; Van der Hulst M; Van der Schueren E; Bartelink H. TI: The influence of the boost in breast-conserving therapy on cosmetic outcome in the EORTC "boost versus no boost" trial. EORTC Radiotherapy and Breast Cancer Cooperative Groups. European Organization for Research and Treatment of Cancer. SO: Int J Radiat Oncol Biol Phys 1999 Oct 1;45(3):677-85. Abstract: PURPOSE: To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT). METHODS AND MATERIALS: In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later. RESULTS: There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04). CONCLUSIONS: These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years. Editor's comments: These two articles (which I had the privilege of commenting on in draft form for the authors) represent an enormous undertaking which I would not have thought possible: that is, to evaluate the cosmetic results in hundereds of women treated in a multi-institutional trial. Further, the authors took the opportunity of this challenge to compare two different methods of scoring cosmetic outcome. The result is a methodological tour de force which is by far the most compulsive, comprehensive such effort of which I am aware. This landmark study will serve as a model for our specialty. ****************** RES: Hoppe 4/00 AU: Horning SJ; Williams J; Bartlett NL; Bennett JM; Hoppe RT; Neuberg D; Cassileth P. TI: Assessment of the Stanford V Regimen and Consolidative Radiotherapy for Bulky and Advanced Hodgkin's Disease: Eastern Cooperative Oncology Group Pilot Study E1492. SO: J Clin Oncol 2000 Mar;18(5):972-80. URL: http://www.jco.org/cgi/content/abstract/18/5/972 PDF: http://www.jco.org/cgi/reprint/18/5/972 Abstract: PURPOSE: This study was performed, in a multi-institutional setting, to evaluate the efficacy and feasibility of the Stanford V chemotherapy regimen plus radiotherapy to bulky Hodgkin's disease sites. PATIENTS AND METHODS: A two-stage design was implemented in a phase II study involving 47 patients with bulky mediastinal stage I/II or stage III/IV Hodgkin's disease. Twelve weeks of the Stanford V chemotherapy regimen were given with consolidative radiotherapy (36 Gy) to lymph nodes >/= 5 cm and/or macroscopic splenic disease. Treatment was administered in one of five institutions participating in the Eastern Cooperative Oncology Group. RESULTS: With a median follow-up of 4.8 years, 45 patients are alive and 40 have been continuously disease-free. The estimated freedom from progression was 87% at 2 years and 85% at 5 years. Overall survival was 96% at 2 and 5 years. There was one death from Hodgkin's disease and one death from an M5 acute leukemia. Six of seven relapsed patients received high-dose therapy and autologous stem-cell transplantation. The freedom from second progression for the seven relapsed patients was estimated at 98% at 3 years. CONCLUSION: Stanford V chemotherapy and consolidative radiotherapy to bulky disease is effective in bulky and advanced Hodgkin's disease in a multi-institutional setting. On this basis, an Intergroup study comparing doxorubicin, bleomycin, vinblastine, and dacarbazine with the Stanford V regimen has been initiated Editor's comments: As a coauthor of this paper, I must declare a potential conflict of interest. I don't like to select a paper on which I am a coauthor, but I do believe the concept of treatment described herein, brief intensive chemotherapy followed by consolidative irradiation is an important approach to the management of advanced stage or bulky Hodgkin's disease. Stanford V includes 3 MOPP drugs (no procarbazine) and 3 ABVD drugs (no dacarbazine) and adds in VP-16. The scheduling is for weekly treatment (alternating myelosuppressive and non-myelosuppressive weeks). The drug treatment program is intense, but since it continues for only 12 weeks, the cumulative dose of each drug, responsible for drug toxicity, is substantially less than the total in 6-8 months of MOPP, ABVD, or one of the alternating or hybrid regimens. We think we get by with much less chemotherapy because of the dose intensity and routine use of radiotherapy. Radiation therapy is an integral part of the Stanford V regimen. All initial sites of disease greater than 5 cm and the spleen (if gross nodules are detected by CT) are treated to a dose of 36 Gy following completion of the chemotherapy. We allow a window of time of only 2-4 (usually 2-3) weeks after chemotherapy before initiating radiation. The radiation fields are defined at the time of initial staging. Those are the fields we treat, even if radiographic (CT or plain film) response in other sites is incomplete. Gallium and/or PET scans are often performed pre- and post-chemo. The Gallium scans are almost always negative after chemo, those that have been positive have always been positive in areas where RT is planned. If gallium was positive outside the intended area of radiation and the RT fields needed to be modified, that patient would be considered a failure of the protocol. Patients with gallium avidity after chemo have become negative with RT. We have been using this approach at Stanford for more than ten years, have treated more than 150 patients, and we continue to be pleased with the results. Patients we see in our long-term follow-up clinic have been remarkably free of complications. This paper describes Stanford V being employed successfully in a multi-institutional setting in ECOG. Based on this ECOG pilot, the Stanford V approach has been adopted as an intergroup trial for bulky and advanced stage Hodgkin's disease, where the alternative treatment arm is ABVD. ****************** Lung/Mediastinum: Turrisi 4/00 AU: Levitan N; Dowlati A; Shina D; Craffey M; Mackay W; DeVore R; Jett J; Remick SC; Chang A; Johnson D. TI: Multi-Institutional Phase I/II Trial of Paclitaxel, Cisplatin, and Etoposide With Concurrent Radiation for Limited-Stage Small-Cell Lung Carcinoma. SO: J Clin Oncol 2000 Mar;18(5):1102. URL: http://www.jco.org/cgi/content/abstract/18/5/1102 PDF: http://www.jco.org/cgi/reprint/18/5/1102 Abstract: PURPOSE: To determine the feasibility of adding paclitaxel to standard cisplatin/etoposide (EP) and thoracic radiotherapy. PATIENTS AND METHODS: Thirty-one patients were enrolled onto this study. During the phase I section of this study, the dose of paclitaxel was escalated in groups of three or more patients. Cycles were repeated every 21 days. For cycles 1 and 2, paclitaxel was administered according to the dose-escalation schema at doses of 100, 135, or 170 mg/m(2) intravenously over 3 hours on day 1. Once the maximum-tolerated dose (MTD) of paclitaxel (for cycles 1 and 2, concurrent with radiation) was determined, that dose was used in all subsequent patients entered onto the phase II section of this study. For cycles 3 and 4, the paclitaxel dose was fixed at 170 mg/m(2) in all patients. On day 2, cisplatin 60 mg/m(2) was administered for all cycles. On days 1, 2, and 3, etoposide 60 mg/m(2)/d (cycles 1 and 2) or 80 mg/m(2)/d (cycles 3 and 4) was administered. Chest radiation was given at 9 Gy/wk in five fractions for 5 weeks beginning on day 1 of cycle 1. Granulocyte colony-stimulating factors were used during cycles 3 and 4 only. RESULTS: Twenty-eight patients were assessable. The MTD of paclitaxel was 135 mg/m(2), with the dose-limiting toxicity being grade 4 neutropenia. Cycles 1 and 2 were associated with grade 4 neutropenia in 32% of courses, with fever occurring in 7% of courses and grade 2/3 esophagitis in 13%. Cycles 3 and 4 were complicated by grade 4 neutropenia in 20% of courses, with fever occurring in 6% of courses and grade 2/3 esophagitis in 16%. The overall response rate was 96% (complete responses, 39%; partial responses, 57%). After a median follow-up period of 23 months (range, 9 to 40 months), the median survival time was 22.3 months (95% confidence interval, 15.1 to 34.3 months). CONCLUSION: The MTD of paclitaxel with radiation and EP treatment is 135 mg/m(2) given over 3 hours. In this schedule of administration, a high response rate and acceptable toxicity can be anticipated. Editor's comments: This is the first published trial attempting to use a triplet, the addition of paclitaxel to widely established doublet cisplatin-etoposide, in combination with concurrent radiotherapy. It is a trial that attempts to incorporate observations with extensive disease patients -- many conducted with Carboplatin instead of cisplatin. Importantly, a lower dose of etoposide has been the price of incorporating the "highly active" taxane as a triplet. The study reports the objectives of toxicity, response and survival. The toxicity is surprisingly modest with only 2% grade three esophagitis during induction. Interestingly, there was more esophagitis reported with the subsequent cycles that employed taxanes -- a definite suggestion that this taxane causes radiation recall esophagitis. The rate remained modest. The hematalogic toxicity was also marked, and required the use of expensive colony stimulating growth factors. Response rates were very high. The survival curves look as if they can be superimposed over current projects using cisplatin-etoposide with concurrent radiotherapy. The two-year figures approximate 40% and the three year figure looks very close to 20% -- not trending toward better outcome. The price of adding the taxane was the reduction in the dose of the most active drug -- etoposide. The use of a triplet and the need for growth factors seem a very current approach, but without substantial measurable gain or even a reasonable hope that these tactics will result in substantial improvement. The RTOG has similar as yet unpublished, un-presented data except at their own meeting. It uses BID radiotherapy and seems to produce better one year survival than the Intergroup results. I've seen information that tells me we need to see their facts with more follow up. Short-term endpoints are going to be less convincing than follow-up sufficient to tell us survival at 24 and 36 months or longer. To my jaundiced view, paclitaxel, as a third drug with a platinum and etoposide (PE) with concurrent radiotherapy, has two pilots showing less than what I would want to see to continue down this path. Other groups are using the doublet carboplatinum and paclitaxel before or after four cycles of PE with escalated once daily doses of radiotherapy in the range of 61-63 Gy. The CALGB uses taxol topotecan for two cycles followed by carbo/etoposide and concurrent 70 Gy. These appear to be tolerable, but there are no formal reports on the toxicity and response. At the end of the day, we need to hear the all important 2 and 3 years survival benchmarks for these ideas before rushing to accept a taxane, with its costs, its toxicities, and its need for growth factor support. We don't need a more expensive way to do the same thing. ****************** GU: Roach 4/00 No Reference Selected ****************** Radiobiology: Withers 4/00 No Reference Selected ****************** Health Services Research: Hayman 4/00 AU: Athas WF; Adams-Cameron M; Hunt WC; Amir-Fazli A; Key CR. TI: Travel distance to radiation therapy and receipt of radiotherapy following breast-conserving surgery. SO: J Natl Cancer Inst 2000 Feb 2;92(3):269-71. URL: http://jnci.oupjournals.org/cgi/content/full/92/3/269 Editor's comments: This relatively short paper describes a study performed by investigators at the New Mexico Tumor Registry, which is part of the SEER program, in which they used a computer program to estimate the shortest distance patients with early stage breast cancer treated with breast conserving surgery would need to travel to reach the nearest radiation therapy facility. They then examined whether those patients who had to travel further for treatment were as likely to receive radiation as those patients who lived closer to a facility. Because their tumor registry is population-based, their analysis included almost all of the patients with early stage breast cancer treated with breast conserving surgery in New Mexico in 1994 and 1995. Not surprisingly, even after adjusting for age, which also tends to be highly negatively correlated with the use of adjuvant radiation therapy, they found a significant decrease in the likelihood of patients receiving radiation therapy as the distance they lived from the nearest facility increased. The authors conclude by noting that they are currently in the process of surveying patients who did not receive adjuvant radiation to gain insight into the reasons why. While there are a number of potential flaws in this study, its results seem to ring true and provide some documentation of what is probably a relatively common problem. If these investigators are able to accurately identify why this commonly occurs, perhaps we, as radiation oncologists, will be able to work more effectively to develop solutions to address this problematic variation in the use of radiation therapy. ****************** Radiation Biophysics: Chen 4/00 No Reference Selected ****************** Brian J. Goldsmith, M.D. Moderator, IROJC