From daemon Tue Sep 14 14:21:20 1999 Received: by net.bio.net (8.9.1a/8.9.1) id OAA22031; Tue, 14 Sep 1999 14:21:20 -0700 (PDT) To: radoncjc@net.bio.net Reply-To: radoncjc@net.bio.net From: staylor@stanford.edu Subject: RADIATION-ONCOLOGY posting problems Message-ID: Date: Tue, 14 Sep 1999 14:15:09 -0700 (Pacific Daylight Time) Dear Readers, Our apologies for the delay in posting this month's Digest. We have been experiencing software problems and hope to fix them soon. Serge Taylor BioSci Administrator From daemon Tue Sep 14 14:32:21 1999 Received: by net.bio.net (8.9.1a/8.9.1) id OAA23825; Tue, 14 Sep 1999 14:32:21 -0700 (PDT) To: radoncjc@net.bio.net Reply-To: radoncjc@net.bio.net From: staylor@stanford.edu Subject: RADIATION-ONCOLOGY posting problems Message-ID: Date: Tue, 14 Sep 1999 14:15:09 -0700 (Pacific Daylight Time) Dear Readers, Our apologies for the delay in posting this month's Digest. We have been experiencing software problems and hope to fix them soon. Serge Taylor BioSci Administrator From daemon Fri Sep 17 08:53:52 1999 Received: (from daemon@localhost) by net.bio.net (8.9.1a/8.9.1) id IAA27718; Fri, 17 Sep 1999 08:53:52 -0700 (PDT) Message-Id: <199909171553.IAA27718@net.bio.net> To: radoncjc@net.bio.net Date: Thu, 16 Sep 1999 06:58:21 -1000 Reply-To: radoncjc@net.bio.net From: Brian J Goldsmith Subject: September 1999 Internet Radiation Oncology Journal Club (IROJC) Date: Mon, 13 Sep 1999 12:28:24 -0400 From: Brian Goldsmith Reply-To: briandeb@bellatlantic.net To: bjg@mhpcc.edu Subject: September 1999 Internet Radiation Oncology Journal Club (IROJC) September 1999 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 52nd 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 Jim Purdy, Ph.D. Editor, Radiation Oncology Physics and Dosimetry ----------------------------------------------------- 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, with the goal of stimulating a professional discussion of these references and their subjects. ------------------------------------------------------------ ARCHIVED IROJC POSTINGS and commentary are available on the World Wide Web! Look for them on http://www.bio.net/ Click on the "Access the BIOSCI/bionet Newsgroups" hyperlink, and then go to "RADIATION-ONCOLOGY/Prototype". Or directly access the RADIATION-ONCOLOGY folder at http://www.bio.net/hypermail/RADIATION-ONCOLOGY/ There's also a freeWAIS search tool at the website, for searching archived postings for keywords or phrases! ------------------------------------------------------------ Commentary Rules: (1) Please cite the subject category in the header of your e-mail message, e.g., Subject: CNS 9/99. (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 9/99 AU: Drolet BA; Esterly NB; Frieden IJ. TI: Hemangiomas in children. SO: N Engl J Med 1999 Jul 15;341(3):173-81. URL: http://www.nejm.org/content/1999/0341/0003/0173.asp Editor's comments: This review article on hemangiomas in children was written primarily for primary care physicians. However it provides a useful review of the pathogenesis, clinical manifestations, complications, management and 73 references which Radiation Oncologists will find a useful resource. Color photographs of various types of cutaneous hemangiomas are presented. While it is a comprehensive review article, this article fail to mention irradiation in any detail other than 2 sentences: "Irradiation was used in the 1940's and 1950's, and many experts subsequently decried the use of aggressive treatment for these self-limiting tumors. Studies demonstrated that the results of irradiation or excisional surgery were worse than the consequences of leaving the tumors untreated." No references are provided for these statements. While it is true that radiation oncologists today are seldom asked to consult on infants and children with hemangiomas, there are instances when low doses of radiation may reverse the life threatening platelet trapping syndrome with coagulopathy know as the Kasabach-Merritt Syndrome. The authors only mention that "The syndrome requires aggressive treatment (often with multiple therapies) and is associated with a high mortality rate". In my own experience, while I rarely recommend treatment with radiotherapy, I have seen critically ill infants who have failed massive doses of steroids, recombinant interferon alfa, and other therapies, respond to treatment with low total doses and small daily fractions of radiation, with rapid reversal of thrombocytopenia and bleeding. Such children should be referred to a Childrens Hospital where supportive care, pediatric dermatology, hematology, and radiation oncology are available. ****************** Head/Neck/Skin: Foote 9/99 AU: Zitsch RP 3rd; Lee BW; Smith RB. TI: Cervical lymph node metastases and squamous cell carcinoma of the lip. SO: Head Neck 1999 Aug;21(5):447-53. Abstract: BACKGROUND: Squamous cell carcinoma of the lip generally has a favorable outcome. The chance of long-term survival is significantly reduced if lymph node metastases develop. Any features that could identify patients having increased risks of occult lymph node metastases would allow more aggressive treatment and, possibly, a better outcome. METHODS: A chart review of lip cancer from this institution identified 1001 patients with squamous cell carcinoma of the lip. This database was used to identify the characteristics that are associated with occult lymph node metastases. RESULTS: Delayed cervical lymph node metastases developed in 40 patients. No significant differences were noted in the frequency of delayed lymph node metastases according to gender, lip subsite, or age less than 40 years. Significant differences were noted in association with the tumor size, tumor differentiation, and local recurrence. CONCLUSIONS: Elective cervical lymphadenectomy is justifiable for higher grade tumors and for locally recurrent tumors. An increase in delayed metastases was observed in patients with tumors greater than 3 cm, but the proportion is not great enough to justify elective neck dissections. Copyright 1999 John Wiley & Sons, Inc. Head Neck 21: 447-453, 1999. ****************** GYN: Petereit 9/99 No Reference Selected ****************** GI / Soft Tissue Sarcoma: Tepper 9/99 No Reference Selected ****************** CNS: Bauman 9/99 AU: Packer RJ, Goldwein J, Nicholson HS, Vezina LG, Allen JC, Ris MD, Muraszko K, Rorke LB, Wara WM, Cohen BH, Boyett JM. TI: Treatment of children with medulloblastomas with reduced-dose craniospinal radiation therapy and adjuvant chemotherapy: a Children's Cancer Group Study. SO: J Clin Oncol 17(7), 1999 2127-2136. URL: http://www.jco.org/cgi/content/abstract/17/7/2127 Abstract: PURPOSE: Medulloblastoma is the most common malignant brain tumor of childhood. After treatment with surgery and radiation therapy, approximately 60% of children with medulloblastoma are alive and free of progressive disease 5 years after diagnosis, but many have significant neurocognitive sequelae. This study was undertaken to determine the feasibility and efficacy of treating children with nondisseminated medulloblastoma with reduced-dose craniospinal radiotherapy plus adjuvant chemotherapy. PATIENTS AND METHODS: Over a 3-year period, 65 children between 3 and 10 years of age with nondisseminated medulloblastoma were treated with postoperative, reduced-dose craniospinal radiation therapy (23.4 Gy) and 55.8 Gy of local radiation therapy. Adjuvant vincristine chemotherapy was administered during radiotherapy, and lomustine, vincristine, and cisplatin chemotherapy was administered during and after radiation. RESULTS: Progression-free survival was 86% ± 4% at 3 years and 79% ± 7% at 5 years. Sites of relapse for the14 patients who developed progressive disease included the local tumor site alone in two patients, local tumor site and disseminated disease in nine, and nonprimary sites in three. Brainstem involvement did not adversely affect outcome. Therapy was relatively well tolerated; however, the dose of cisplatin had to be modified in more than 50% of patients before the completion of treatment. One child died of pneumonitis and sepsis during treatment. CONCLUSION: These overall survival rates compare favorably to those obtained in studies using full-dose radiation therapy alone or radiation therapy plus chemotherapy. The results suggest that reduced-dose craniospinal radiation therapy and adjuvant chemotherapy during and after radiation is a feasible approach for children with nondisseminated medulloblastoma. Editor's comments: In a multi-institutional study of reduced dose radiation and chemotherapy for children with favourable risk (no supratentorial PNET, no CSF dissemination) excellent (80%) 5 year DFS survival was noted. The importance of an adequate MRI for spinal staging was again re-emphasized as retrospective analysis of patients revealed that 5/14 who failed either had actual evidence of dissemination on the pretreatment MRI (n equals 3) or inadequate studies due to motion artifact (n equals 2). Exclusion of those 5 patients produced a 5 year DFS of 90%. This trial, combined with a recent subanalysis of the POG randomized trial which demonstrated improved neurocognitive function for patients receiving reduced dose craniospinal irradiation (Mulhern, J Clin Oncol 16(5) 1723-1728,1 1998, http://www.jco.org/cgi/content/abstract/16/5/1723) argues in favour of combined modality therapy for favourable risk patients with medulloblastoma. ****************** Physics/Dosimetry: Purdy 9/99 No Reference Selected ****************** Breast: Recht 9/99 AU: Recht A, Gray R, Davidson NE, Fowble BL, Solin LJ, Cummings FJ, Falkson G, Falkson HC, Taylor SG, Tormey DC. TI: Locoregional failure 10 years after mastectomy and adjuvant chemotherapy with or without tamxifen without irradiation: experience of the Eastern Cooperative Oncology group. SO: J Clin Oncol 1999;17:1689-1700. URL: http://www.jco.org/cgi/content/abstract/17/6/1689 Abstract: PURPOSE: To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS: The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS: A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION: LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens. Editor's comments: This month's choice examines the risk of local-regional failure following mastectomy in patients receiving chemotherapy in what is so far the largest such series of patients. We undertook this study in large part because of the controversy created by the publications of the Danish 82b and British Columbia randomized trials as to whether postmastectomy radiotherapy should be used routinely in node-positive patients. As we discuss in our article, LRF rates in those two studies were substantially higher than in a number of retrospective studies. Hence, the applicability of these results to other institutions was questioned. The current series shows that LRF rates in a predominantly American multi-institutional surgical experience was lower than for thses two trials. However, these rates were not negligible either, as some had thought. My greatest satisfaction in this project was in our ability to look at a host of clinical and tumor-related factors in relationship to the risk of LRF, which has rarely been done, in a large data-set. Unfortunately, we did not have detailed pathologic information (such as grade, margin status, lymphovascular invasion, etc) which I believe are also influential in this regard. Other groups are working on this problem also, and we hope this effort will spark more investigation of this important but somewhat neglected topic. Finally, having this platform lets me again express my great thanks to my collaborators, particularly Bob Gray, who patiently and without protest e-mailed scores of tables and analyses to me, and Barbara Fowble, who started this project more than 10 years before I became involved with ECOG (see J Clin Oncol 1988;6:1107-17, http://www.jco.org/cgi/content/abstract/6/7/1107). ****************** RES: Hoppe 9/99 AU: Grange F; Hedelin G; Joly P; Beylot-Barry M; D'Incan M; Delaunay M; Vaillant L; Avril MF; Bosq J; Wechsler J; Dalac S; Grosieux C; Franck N; Esteve E; Michel C; Bodemer C; Vergier B; Laroche L; Bagot M. TI: Prognostic factors in primary cutaneous lymphomas other than mycosis fungoides and the Sezary syndrome. The French Study Group on Cutaneous Lymphomas. SO: Blood 1999 Jun 1;93(11):3637-42. Abstract: Prognostic studies of primary cutaneous lymphomas (PCL) other than mycosis fungoides (MF) and the Sezary syndrome (SS; non-MF/SS PCL) have been mainly performed on subgroups or on small numbers of patients by using univariate analyses. Our aim was to identify independent prognostic factors in a large series of patients with non-MF/SS PCL. We evaluated 158 patients who were registered in the French Study Group on Cutaneous Lymphomas database from January 1, 1986 to March 1, 1997. Variables analyzed for prognostic value were: age; sex; type of clinical lesions; maximum diameter, location, and number of skin lesions; cutaneous distribution (ie, local, regional, or generalized); prognostic group according to the European Organization for Research and Treatment of Cancer (EORTC) classification for PCL; B- or T-cell phenotype; serum lactate dehydrogenase (LDH) level; and B symptoms. Univariate and multivariate analyses were performed using a model of relative survival. Forty-nine patients (31%) died. The median relative survival time was 81 months. In univariate analysis, EORTC prognostic group, serum LDH level, B symptoms, and variables related to tumor extension (ie, distribution, maximum diameter, and number of skin lesions) were significantly associated with survival. When these variables were considered together in a multivariate analysis, EORTC prognostic group and distribution of skin lesions remained statistically significant, independent prognostic factors. This study confirms the good predictive value of the EORTC classification for PCL and shows that the distribution of skin lesions at initial evaluation is an important prognostic indicator. Editor's comments: Many of the non-MF cutaneous lymphomas are just becoming well defined. This is a pretty good paper to describe existing clinical entities. The most important prognostic factors were clinical classification and stage (localized vs. generalized, i.e., stage IE vs. IV). Treatment is not dealt with, but should clearly be influenced by both of these variables. Guidance for appropriate therapy is more likely to come from other papers that deal with single disease entities. ****************** Lung/Mediastinum: Turrisi 9/99 AU: Auperin A; Arriagada R; Pignon JP; Le Pechoux C; Gregor A; Stephens RJ; Kristjansen PE; Johnson BE; Ueoka H; Wagner H; Aisner J. TI: Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group [see comments]. SO: N Engl J Med 1999 Aug 12;341(7):476-84. URL: http://www.nejm.org/content/1999/0341/0007/0476.asp EDITORIAL: N Engl J Med 1999 Aug 12;341(7):524-6. EDITORIAL URL: http://www.nejm.org/content/1999/0341/0007/0524.asp Abstract: BACKGROUND: Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. METHODS: We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. RESULTS: The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P equals 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P less than 0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P less than 0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend equals 0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P equals 0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. CONCLUSIONS: Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission. Editor's comments: For the doubters, this really cements the fact that prophylactic cranial irradiation is good for the health of patients in CR after treatment for SCLC. There is in fact a survival advantage nearly equal to that produced with thoracic radiotherapy. The naysayers are still wringing their hands and anxious about neurotoxicity. We now know that SCLC patients have neurocognitive deficits at diagnosis before any treatment. The fact that two of the studies composing the meta-analysis failed to detect a substantial difference after treatment seems to have had no influence. Dr. Carney in his editorial identifies two authors that have been booing PCI for years, one suggested that follow-up imaging was appropriate. Another critic at the ASCO presentation continued to assert that the safety of PCI has not been clearly established. I would argue that the safety of observation is unproven and in fact unacceptable. Even if there was no survival advantage (and there is), decreasing brain metastasis has to be an advantage to your neurocognitive health and quality of life. People with brain mets have difficulty with trail-making and serial sevens, but we forget that these are neurocognitive deficits that occur in 50 - 60% of those observed -- this is not a safe strategy. Serial images are expensive and also find brain mets after quality of life has suffered and deficits are extant and commonly not remedies with our pound of cure. The "do no harm" crowd now have to eat crow and accept PCI because doing nothing in this case does harm. Game, set and match for PCI. The issues are when to give it, how much to give, and in what fraction sizes (the subjects for trials, not my comments at this point). Dr. Carney writes a very nice editorial, save for the fact that he misquotes the BID survival -- it is 47% and 26% for 2 and 5 years respectively on the intergroup trial (not 44% and 22%). He also excepts elderly patients from PCI -- no reference, and no cogent or proven reason. I contend that all limited SCLC patients with even excellent PR should get it, regardless of age, and that all with extensive disease in CR should get it. You pick the dose and the fractions, but do it after completion of systemic therapy. More on extensive disease next month. ****************** GU: Roach 9/99 No Reference Selected ****************** Radiobiology: Withers 9/99 AU: Raaphorst GP; Wilkins DE; Mao JP; Miao JC; E C; Ng CE. TI: Evaluation of cross-resistance between responses to cisplatin, hyperthermia, and radiation in human glioma cells and eight clones selected for cisplatin resistance. SO: Radiat Oncol Investig 1999;7(3):153-7. Abstract: Human glioma cells were exposed to stepwise increasing concentrations of cisplatin and given a final, acute, high concentration treatment of cisplatin. From the surviving cells, eight cisplatin resistant clones were selected. These clones demonstrated a range of cisplatin sensitivities that were retained in the absence of cisplatin when cells were continually passaged. These cells were tested for cross-resistance to radiation and hyperthermia at 42 and 45 degrees C. The data showed that seven of the eight clones were also more radioresistant than the parental line, while one was more radiosensitive. The degree of cisplatin resistance was not related to the degree of radiation resistance. For hyperthermia at 42 and 45 degrees C, some of the clones were slightly more resistant than the parental line, while one clone was much more sensitive. This was not the same clone that was radiosensitive. In conclusion, there was no direct correlation between cisplatin resistance, radiation resistance, and hyperthermia response, although some of the clones were resistant to all three treatments. Editor's comments: There is a tendency for medical oncologists, and also radiation oncologists, to equate chemoresistance with radioresistance. Since the most common cause of chemoresistance lies in the ability of the cell membrane to rid the cell of the chemotherapy drug, there is no reason to predict such a correlation. (Cells can't pump out radiation.) The authors studied this question in vitro and conclude that, although there is a spectrum of radiation sensitivities among the 8 cisplatin-resistant cell lines studied, there is not a correlation between the development of chemo- and radiation resistance. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC