From owner-radoncjc@net.bio.net Thu May 4 00:10:33 2000 Return-Path: Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 110) id 58B1017AC6; Thu, 4 May 2000 00:10:30 +0100 (BST) Received: by mercury.hgmp.mrc.ac.uk (Postfix, from userid 1) id D69A717A58; Thu, 4 May 2000 00:10:28 +0100 (BST) To: radoncjc@net.bio.net From: Brian@hgmp.mrc.ac.uk, Goldsmith@hgmp.mrc.ac.uk, MD@hgmp.mrc.ac.uk Reply-To: radoncjc@net.bio.net Date: 5/3/00 4:01PM Subject: May 2000 Internet Radiation Oncology Journal Club (IROJC) Message-Id: <20000503231028.D69A717A58@mercury.hgmp.mrc.ac.uk> Sender: owner-radoncjc@net.bio.net Precedence: bulk May 2000 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 60th 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 5/00. (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 (goldsmithb@radiological.com) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 5/00 AU: Landau D, Vini L, A'Hern R, Harmer C. TI: Thyroid cancer in children: the Royal Marsden Hospital experience. SO: Eur J Cancer 2000 Jan;36(2):214-20. Abstract: The first child with well-differentiated thyroid cancer treated at the Royal Marsden Hospital presented in 1917. Since that time 30 children under the age of 16 years have been treated over a period during which many new treatments have been introduced. We have reviewed their management and outcome. The median follow-up is 22.5 years (range: 1-66). The median time to recurrence was 7 years (range: 2-44). There were events up to 44 years after presentation. The risk of recurrence was higher in children aged 10 years or younger [HR 3.45, 95% CI (1.04-11.11) P = 0.03]. Thyroid stimulating hormone (TSH) suppression was the only intervention to be shown to reduce the recurrence rate [HR 11, 95% CI (2.27-50) P = 0.0003]. The median overall survival is 53 years. The only presenting feature predictive of poorer survival was the presence of metastases (HR 28.96, 95% CI 2.51-334, P < 0.001). Patients who developed recurrence had a higher risk of death (HR 9.90, 95% CI 0.98-100, P = 0.02) and a shorter median survival of 30 years. No therapeutic intervention could be shown statistically to impact on survival. Our recommendation for treatment is total or near-total thyroidectomy for all patients and radioiodine ablation for all except those with early T stage node-negative disease aged over 10 years. Modified neck dissection is recommended for children with clinically positive neck nodes and TSH suppression for all. Follow-up with serial thyroglobulin measurement shouldbe lifelong. Editor's comments: Although thyroid cancer in children is rare, when we do consult on such a child it is nice to have a handy reference available. This single institution report of 30 children, <16 years of age, provides the data and careful analysis that clinicians need when asked for advice. It is of particular usefulness having median followup of 22.5 years and confirms the need for aggressive initial management, with excellent overall outcome. ****************** Head/Neck/Skin: Foote 5/00 AU: Jeremic B, Shibamoto Y, Milicic B, Nikolic N, Dagovic A, Aleksandrovic J, Vaskovic Z, Tadic L. TI: Hyperfractionated radiation therapy with or without concurrent low-dose daily cisplatin in locally advanced squamous cell carcinoma of the head and neck: a prospective randomized trial. SO: J Clin Oncol 2000 Apr;18(7):1458-64. URL: http://www.jco.org/cgi/content/abstract/18/7/1458 PDF: http://www.jco.org/cgi/reprint/18/7/1458 ****************** GYN: Petereit 5/00 AU: Pickel H; Lahousen M; Petru E; Stettner H; Hackl A; Kapp K; Winter R. TI: Consolidation radiotherapy after carboplatin-based chemotherapy in radically operated advanced ovarian cancer. SO: Gynecol Oncol 1999 Feb;72(2):215-9. Abstract: OBJECTIVE: The aim of the study was to evaluate the effect of additional radiotherapy after chemotherapy on the relapse-free and overall survival rates of patients with advanced ovarian cancer. METHODS: Between 1985 and 1992 64 patients with radically operated ovarian cancers (4 stage IC, 2 stage II, 54 stage III, and 4 stage IV) were enrolled in a randomized study. Radical surgery comprised total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and pelvic and paraaortic lymphadenectomy. All patients received adjuvant chemotherapy with carboplatin IV 400 mg/m2, epirubicin IV 70 mg/m2 on day 1 and prednimustine orally 100 mg/m2 on days 3 to 7 at 1-month intervals. Thirty-two patients without residual disease were randomized to whole abdominal radiation (30 Gy, administered over 4 weeks). An additional 21.6 Gy were delivered to the pelvis and 12 Gy to the paraaortic region up to the diaphragm for total doses of 51.6 and 42 Gy, respectively. Cancer-related survival was calculated with the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The relapse-free and overall survival rates of patients who received adjuvant chemoradiotherapy were significantly higher than those of patients who received adjuvant chemotherapy only (68% vs 56% at 2 years and 49% vs 26% at 5 years, P = 0.013, and 87% vs 61% at 2 years and 59% vs 33% at 5 years, P = 0.029). The differences were most pronounced in patients with stage III disease (77% vs 54% at 2 years and 45% vs 19% at 5 years, P = 0. 0061, and 88% vs 58% at 2 years and 59% vs 26% at 5 years, P = 0. 012). Toxicities were acceptable. CONCLUSION: Sequential combination of platinum-based chemotherapy with open-field abdominal radiotherapy is a promising adjuvant regimen for patients with advanced ovarian cancer. Copyright 1999 Academic Press. Editor's comments: This small randomized study from the University of Graz revealed intriguing results supporting the efficacy of consolidative whole abdominal radiotherapy (WAR). Patients received planned consolidative WAR, as opposed to salvage WAR after recurrence. It is of interest that this study revealed an approximate 25% improvement in survival and relapse-free survival with WAR after 6 cycles of chemotherapy compared to no further chemotherapy at 5 years, whereas other studies have not observed such overwhelmingly positive results. I have a number of comments/criticisms: 1) a strong selection bias was introduced in that a total of 94 patients were evaluated, but only 64 patients were randomized after completing 6 cycles of chemotherapy; only patients eligible were those that completed adjuvant chemotherapy, had no evidence of recurrent disease and adequate bone marrow reserve, 2) the chemotherapy used was not standard, 3) stage III patients were not subdivided into subgroups, 4) 59% of patients overall had positive para-aortic disease, and yet a survival of 59% was observed in those patients who were radiated-much higher than other published series, 5) 31% of patients were suboptimally debulked (residual disease > 2 cm, with about another 25% of patients debulked to disease < 2cm; therefore, it is likely that over 50% of patients were suboptimally debulked-disease > 1 cm, 6) the whole abdominal doses and dose per fraction was rather high: WAR-30 Gy @ 1.5 Gy/Fx, with 42.6 Gy to the para-aortics and 51.6 Gy to the pelvis; treatment breaks: planned 2 week break mandatory, 5 patients did not complete the radiotherapy, 7) only 1 of 32 patients who received WAR developed a small bowel obstruction that required surgery-surprinsingly low. Despite these concerns a definite improvement in survival was observed-especially for the stage III patients. While the patient selection bias was less than ideal, the study does confirm what believers in WAR, including myself, preach: patient selection! Typical candidates for WAR are those who have microscopic residual disease (< 1 cm), are medically fit and have been thoroughly and completely staged by a gynecologic oncologist. It is unclear from the study if these patients were surgically managed by a general gynecologist or a gynecologic oncologist. A very interesting finding is the observation that patients who were not optimally debulked still did reasonably well. In fact, the multivariate analysis performed did not demonstrate the amount of residual disease was of prognostic significance. This is clearly in contrast to numerous other studies which have revealed the opposite. The authors suggest that this is because the chemotherapy converted these suboptimal patients into "optimal" ones. What is the take home message: I believe this study is additional data that supports the use of WAR in highly selected patients. One of the advantages of consolidative as opposed to salvage WAR is the markedly lower complication rates-especially if salvage WAR is given after a second-look surgery, and higher cure rates. The significant complication rates after adjuvant and/or consolidative WAR are 5% (actuarial rates) at 5 years as opposed to 10 to 15% after a second surgery. Many gynecologic radiation oncologists have submitted ovarian protocols that investigate WAR in some fashion to the GOG ovarian committee. Unfortunately, the bias is so strong against WAR that none these proposed studies have been supported. I personally would like to see the best chemotherapy compared to the best chemotherapy and consolidative WAR. This seems more rational, with a wider therapeutic window, than a bone marrow rescue after marrow-ablative chemotherapy! ****************** GI / Soft Tissue Sarcoma: Tepper 5/00 No Reference Selected ****************** CNS: Bauman 5/00 No Reference Selected ****************** Breast: Recht 5/00 No Reference Selected ****************** RES: Hoppe 5/00 AU: Girinsky T, Benhamou E, Bourhis JH, Dhermain F, Guillot-Valls D, Ganansia V, Luboinski M, Perez A, Cosset JM, Socie G, Baume D, Bouaouina N, Briot E, Beaudre A, Bridier A, Pico JL. TI: Prospective randomized comparison of single-dose versus hyperfractionated total-body irradiation in patients with hematologic malignancies. SO: J Clin Oncol. 2000 Mar;18(5):981-6. URL: http://www.jco.org/cgi/content/abstract/18/5/981 PDF: http://www.jco.org/cgi/reprint/18/5/981 Abstract: PURPOSE: Fractionated total-body irradiation (HTBI) is considered to induce less toxicity to normal tissues and probably has the same efficacy as single-dose total-body irradiation (STBI) in patients with acute myeloid leukemia. We decided to determine whether this concept can be applied to a large number of patients with various hematologic malignancies using two dissimilar fractionation schedules. PATIENTS AND METHODS: Between December 1986 and October 1994, 160 patients with various hematologic malignancies were randomized to receive either a 10-Gy dose of STBI or 14.85-Gy dose of HTBI. RESULTS: One hundred forty-seven patients were assessable. The 8-year overall survival rate and cause-specific survival rate in the STBI group was 38% and 63.5%, respectively. Overall survival rate and cause-specific survival rate in the HTBI group was 45% and 77%, respectively. The incidence of interstitial pneumonitis was similar in both groups. However, the incidence of veno-occlusive disease (VOD) of the liver was significantly higher in the STBI group. In the multivariate analysis with overall survival as the end point, the female sex was an independent favorable prognostic factor. On the other hand, when cause-specific survival was considered as the end point, the multivariate analysis demonstrated that sex and TBI were independent prognostic factors. CONCLUSION: The efficacy of HTBI is probably higher than that of STBI. Both regimens induce similar toxicity with the exception of VOD of the liver, the incidence of which is significantly more pronounced in the STBI group. Editor's comments: There aren't many clinical trials in bone marrow transplantation that ask a radiation therapy question, so this report is notable. Patients were randomixed to single dose TBI (10 Gy; lung dose 8 Gy) or fractionated TBI (1.35 Gy x 11 in 5 days; 14.85 Gy total; lung dose 9 Gy). There was no difference in pneumonitis, but significantly less VOD in the fractionated group. In addition, there was a suggestion that the efficacy of the fractionated program was greater, perhaps because of the higher dose that could be employed. ****************** Lung/Mediastinum: Turrisi 5/00 No Reference Selected ****************** GU: Roach 5/00 No Reference Selected ****************** Radiobiology: Withers 5/00 No Reference Selected ****************** Health Services Research: Hayman 5/00 AU: Earle C; Coyle D; Smith A; Agboola O; Evans WK. TI: The cost of radiotherapy at an Ontario regional cancer centre: a re-evaluation. SO: Crit Rev Oncol Hematol 1999 Nov;32(2):87-93. Editor's comments: In this paper, Earle and colleagues estimated the average cost of treatment with a fraction of radiation by allocating all costs attributable to the radiation oncology department of the Ottawa Regional Cancer Centre over a one year period and then dividing this figure by the total number of fractions delivered during that year. For fiscal year 1995/1996, they estimated the average cost per fraction to be $138 CDN. Not surprisingly, the majority of the cost (68%) was due to personnel costs. Interestingly, when their cost estimate is compared to an estimate from another Canadian study performed in 1984 after adjusting for inflation, the average cost of a fraction in Ontario appears to have gone down, not up, over time (from $176 in 1984 to $138 in 1996). They attribute this decline to increased efficiency in the delivery of radiotherapy (i.e., greater number of fractions delivered per machine). This paper is of interest because it adds to a growing body of literature dealing with estimating the cost of delivering external beam radiation therapy. Many of the prior studies are quite old and it is important to have more up-to-date estimates because practice patterns, and their associated costs, can change over time. As acknowledged by the authors, the primary limitation of this study is that they were only able to estimate the average cost per fraction. Obviously, not all courses of treatment are equally costly to plan and deliver and it would be helpful to be able to have site- and technique-specific cost estimates. Nevertheless, as reimbursement declines and interest in assessing the cost-effectiveness of what we do grows, it will be increasingly important to have up-to-date estimates of the cost of delivering external beam treatments. ****************** Radiation Biophysics: Chen 5/00 No Reference Selected ****************** Brian J. Goldsmith, M.D. Moderator, IROJC