From daemon Thu May 6 08:19:38 1999 Received: (from daemon@localhost) by net.bio.net (8.9.1a/8.9.1) id IAA18697; Thu, 6 May 1999 08:19:38 -0700 (PDT) Message-Id: <199905061519.IAA18697@net.bio.net> To: radoncjc@net.bio.net Date: Tue, 4 May 1999 10:23:49 -1000 Reply-To: radoncjc@net.bio.net From: Brian J Goldsmith Subject: May 1999 Internet Radiation Oncology Journal Club (IROJC) May 1999 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 48th 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 Perry Grigsby, 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 David Larson, 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 5/99. (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 (bjg@mhpcc.edu) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 5/99 AU: Ekert H, Toogood I, Downie P, Smith PJ, Macfarlane S, White L. TI: High incidence of treatment failure with vincristine, etoposide, epirubicin, and prednisolone chemotherapy with successful salvage in childhood Hodgkin disease. SO: Med Pediatr Oncol 1999 Apr;32(4):255-8. Abstract: BACKGROUND AND PROCEDURE: In an attempt to further reduce the long-term toxicity of chemotherapy for childhood Hodgkin disease (HD), the Australian and New Zealand Children's Cancer Study Group between 1990 and 1996 enrolled 53 children with biopsy-proven and imaging-staged HD into a chemotherapy-only treatment regimen using 5-6 courses of vincristine, etoposide, epirubicin, and prednisolone (VEEP). RESULTS: There were 23 events in these children with 3 progressive disease (PD), 8 partial remissions (PR), and 12 relapses. In the stage I patients, there were 8 events (35%). There was no association between the number of events and the stage of HD. Massive mediastinal disease at diagnosis was present in 16 patients, 11 of whom had an event with 3 PD, 3 PR, and 5 relapses. For all patients with an event at 6-24-month follow-up, all but two patients were salvaged with either alkylating agent-based chemotherapy alone or with irradiation and chemotherapy. The event-free survival for the whole group with median follow-up of 33 months was 59%, but only 31% for massive mediastinal disease. Disease-free survival was 78% and overall survival at 60 months was 92%, with one death due to drug-induced aplasia and another from acute myeloid leukemia. CONCLUSIONS: We conclude that VEEP chemotherapy in childhood HD used as the only treatment modality has an unacceptably high treatment failure rate in patients with massive mediastinal disease and 35% incidence of treatment failure in stage I disease. Editor's comments: The leaders from Australia and New Zealand have long searched for a successful multiagent chemotherapy program for children with Hodgkin's Disease, so to avoid using radiation therapy. The VEEP program without irradiation was designed so to avoid toxicity from alkylating agent based chemotherapy and radiotherapy. Unfortunately the EFS and DFS using this chemotherapy alone combination is clearly inadequate, as the authors conclude. They also conclude they will continue to use chemotherapy alone combinations in their subsequent studies. They emphasize the high salvage rate for those who do suffer a relapse. What they do not mention is that the complication rate following the aggressive salvage therapy needed to treat relapsed Hodgkin's disease is higher than that observed with planned combined modality therapy. Many centers around the world have now reported the highest EFS, DFS, and Survival rates come from combined modality therapy, as opposed to that achieved from chemotherapy alone programs. Most oncologists today agree that the preferred therapy for the vast majority of children with Hodgkins Disease is risk adapted, combined modality therapy using low dose, involved field radiation with limited cycles of non-toxic chemotherapy. ****************** Head/Neck/Skin: Foote 5/99 AU: Kwong DL, Nicholls J, Wei WI, Chua DT, Sham JS, Yuen PW, Cheng AC, Wan KY, Kwong PW, Choy DT. TI: The time course of histologic remission after treatment of patients with nasopharyngeal carcinoma. SO: Cancer 1999 Apr 1;85(7):1446-53. URL: http://canceronline.wiley.com/cgi-bin/abstracts/v85n7/v85n7p1446.abstract.html Abstract: BACKGROUND: The objective of this study was to define the time course of histologic remission and to evaluate the prognostic significance of delayed histologic remission of patients with nasopharyngeal carcinoma (NPC). METHODS: Between 1986-1994, 803 patients underwent serial postradiotherapy nasopharyngeal biopsies. Patients with positive histology underwent repeated biopsies every 2 weeks until the biopsies were found to be negative or, if remission did not occur by the 12th week after radiotherapy, treatment was initiated for persistent disease. Patients with positive histology found after the fifth week but who achieved spontaneous remission before the twelfth week were considered to have delayed histologic remission. Negative histology by the sixth week was considered early histologic remission. The outcome of patients with delayed histologic remission, early histologic remission, and persistent disease were compared. RESULTS: Six hundred and seventeen patients (76.8%) had negative histology within 12 weeks of the completion of radiotherapy and 55 (6.9%) had persistent disease at Week 12. In 131 patients (16.3%) spontaneous remission was observed in repeat biopsies after initial positive histology. With increasing time after radiotherapy, the incidence of positive histology decreased but more patients were found to have persistent disease. Patients with early and delayed histologic remission had 5-year NPC control rates of 82.4% and 76.8%, respectively (P equals 0.35) versus a 40% NPC control rate among patients with persistent disease (P less than 0.001). The 5-year survival rates were 75.3%, 79.4%, and 54.2%, respectively, for the 3 groups (P less than 0.001). CONCLUSIONS: A high proportion of early positive histology remitted spontaneously. Delayed histologic remission in NPC patients is not a poor prognostic factor and additional treatment is not necessary. A confirmatory biopsy at 10 weeks is recommended before the initiation of salvage treatment. Editor's comments: This is a prospective study in which 803 patients with NPC treated with radiation therapy (147 received neoadjuvant chemotherapy) underwent serial, endoscopically guided, multiple biopsies from the nasopharynx after completion of treatment. The median radiation dose to the nasopharynx was 61 Gy and no information was given regarding fractionation so the result may not apply to North American patients. In addition, there is no information regarding histologic type (WHO) which also raises concerns regarding applicability to North American patients. 77% of the patients had negative biopsies and 23% had positive biopsies. 131 of the 186 patients (70%) with positive biopsies after treatment underwent "spontaneous remission" and became negative on subsequent biopsy with no additional treatment usually by the tenth week post treatment. There was no correlation between positive biopsy post treatment and original T-stage. 49 patients with an initial "negative" biopsy had a subsequent positive biopsy in the first 12 weeks after treatment (usually 2 weeks after the first biopsy), yielding a false-negative rate of 26%. There was no difference in local control or survival when analyzed by early remission (first biopsy negative) versus delayed remission (first biopsy positive but biopsy eventually negative within 12 weeks). The authors suggest that, in the Chinese population treated to a median dose of 61 Gy, 70% of post treatment positive biopsies will become negative with no additional treatment up until the tenth week. After this, a positive biopsy indicates persistent disease and warrants additional treatment. Two biopsies should be done since there is a 26% false-negative rate. They recommend waiting 8-10 weeks after treatment before performing the first biopsy. By doing this, some patients with an early (4-6 week) positive biopsy can be spared salvage treatment. This study also raises questions about the real efficacy of salvage Treatment reported in the literature especially in patients who have positive biopsies near the completion of radiation therapy. ****************** GYN: Grigsby 5/99 No Reference Selected ****************** GI / Soft Tissue Sarcoma: Tepper 5/99 No Reference Selected ****************** CNS: Larson 5/99 No Reference Selected ****************** Physics/Dosimetry: Purdy 599 No Reference Selected ****************** Breast: Recht 5/99 AU: Paik S, Bryant J, Park C, Fisher B, Tan-Chiu E, Hyams D, Fisher ER, Lippman ME, Wickerham DL, Wolmark N. TI: erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer. SO: J Natl Cancer Inst 1998 Sep 16;90(18):1361-70. URL: http://jnci.oupjournals.org/cgi/content/abstract/90/18/1361 Abstract: BACKGROUND: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. METHODS: In National Surgical Adjuvant Breast and Bowel Project protocol B-11, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF). Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS). Reported P values are two-sided. RESULTS: Overexpression of erbB-2 (i.e., positive Immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P equals .02), lack of estrogen receptors (P equals .008), and the number of positive lymph nodes (P equals .0001). After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors- DFS: relative risk of failure (RR) equals 0.60 (95% confidence interval [CI] equals 0.44-0.83), P equals .001; survival: RR equals 0.66 (95% CI equals 0.47-0.92), P equals .01; RFS: RR equals 0.58 (95% CI equals 0.42-0.82), P equals .002; DDFS: RR equals 0.61 (95% CI equals 0.44-0.85), P equals .003. However, it was not significant for patients with erbB-2-negative tumors-DFS: RR equals 0.96 (95% CI equals 0.75-1.23), P equals .74; survival: RR equals 0.90 (95% CI equals 0.69-1.19), P equals .47; RFS: RR equals 0.88 (95% CI equals 0.67-1.16), P equals .37; DDFS: RR equals 1.03 (95% CI equals 0.79-1.35), P equals .84. Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P equals .02) and DDFS (P equals .02) but not for survival (P equals .15) or RFS (P equals .06). CONCLUSIONS: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer. AU: Thor AD, Berry DA, Budman DR, Muss HB, Kute T, Henderson IC, Barcos M, Cirrincione C, Edgerton S, Allred C, Norton L, Liu ET. TI: erbB-2, p53, and efficacy of adjuvant therapy in lymph node-positive breast cancer. SO: J Natl Cancer Inst 1998 Sep 16;90(18):1346-60. URL: http://jnci.oupjournals.org/cgi/content/abstract/90/18/1346 Abstract: BACKGROUND: We have previously reported that high expression of the erbB-2 gene (also known as HER-2/neu and ERBB2) in breast cancer is associated with patient response to dose-intensive treatment with cyclophosphamide, doxorubicin (Adriamycin), and 5-flurouracil (CAF) on the basis of short-term follow-up of 397 patients (set A) with axillary lymph node-positive tumors who were enrolled in Cancer and Leukemia Group B (CALGB) protocol 8541. METHODS: To validate those findings, we conducted immunohistochemical analyses of erbB-2 and p53 protein expression in an additional cohort of 595 patients (set B) from CALGB 8541, as well as a molecular analysis of erbB-2 gene amplification in tumors from all patients (sets A and B). Marker data were compared with clinical, histologic, treatment, and outcome data. RESULTS: Updated analyses of data from set A (median follow-up, 10.4 years) showed an even stronger interaction between erbB-2 expression and CAF dose, by use of either immunohistochemical or molecular data. A similar interaction between erbB-2 expression and CAF dose was observed in all 992 patients, analyzed as a single group. However, for set B alone (median follow-up, 8.2 years), results varied with the method of statistical analysis. By use of a proportional hazards model, the erbB-2 expression-CAF dose interaction was not significant for all patients. However, in the subgroups of patients randomly assigned to the high- or The moderate-dose arms, significance was achieved. When patient data were adjusted for differences by use of a prognostic index (to balance an apparent failure of randomization in the low-dose arm), the erbB-2 expression-CAF dose interaction was significant in all patients from the validation set B as well. An interaction was also observed between p53 immunopositivity and CAF dose. CONCLUSIONS: The hypothesis that patients whose breast tumors exhibit high erbB-2 expression benefit from dose-intensive CAF should be further validated before clinical implementation. Interactions between erbB-2 expression, p53 expression, and CAF dose underscore the complexities of predictive markers where multiple interactions may confound the outcome. Editor's comments: These two articles appeared in the same issue of the Journal of the National Cancer Institute. They suggest that the expression of erbB-2 (or HER2) is a marker of relative resistence ot non-doxorubicin containing regimens and low-dose doxorubicin-containing regimens. Overexpression of p53 (or TP53) also appears to decrease the effectiveness of low-dose doxorubicin regimens. Of note, a study in which patients with locally-advanced disease received concurrent 5FU and radiotherapy also showed a greater proportion of pathologic responses in patients without p53 overexpression (Formenti et al, Int J Radiat Oncol Biol Phys 1997;1059ff). However, a paper from the Institut Curie reporting on findings from their S6 trial found no impact of either erbB-2 or p53 status on the response to preoperative chemotherapy (using FAC) or radiotherapy (Rozan et al, Int J Cancer 1998;79:27-33). Hence, the clinical significance of overexpression of either gene product remains unsettled in my mind. ****************** RES: Hoppe 5/99 No Reference Selected ****************** Lung/Mediastinum: Turrisi 5/99 No Reference Selected ****************** GU: Roach 5/99 AU: Zelefsky MJ, Wallner KE, Ling CC, Raben A, Hollister T, Wolfe T, Grann A, Gaudin P, Fuks Z, Leibel SA. TI: Comparison of the 5-year outcome and morbidity of three-dimensional conformal radiotherapy versus transperineal permanent iodine-125 implantation for early-stage prostatic cancer. SO: J Clin Oncol 1999 Feb;17(2):517-22. URL: http://www.jco.org/abs17_2/v17n2p517.html Abstract: PURPOSE: To compare the prostate-specific antigen (PSA) relapse-free survival outcome and incidence of late toxicity for patients with early-stage prostate cancer treated at a single institution with either three-dimensional conformal radiotherapy (3D-CRT) or transperineal permanent implantation (TPI) with iodine-125 seeds. MATERIALS AND METHODS: Patients with favorable-risk prostate cancer, defined as a pretreatment PSA of less than or equal to 10.0 ng/mL, Gleason score of 6 or lower, and stage less than or equal to T2b, were selected for this analysis. Between 1989 and 1996, 137 such patients were treated with 3D-CRT and 145 with TPI. The median ages of the 3D-CRT and TPI groups were 68 years and 64 years, respectively. The median dose of 3D-CRT was 70.2 Gy, and the median implant dose was 150 Gy. Prostate-specific antigen relapse was defined according to the American Society of Therapeutic Radiation Oncology Consensus Statement, and toxicity was graded according to the Radiation Therapy Oncology Group morbidity scoring scale. The median follow-up times for the 3D-CRT and TPI groups were 36 and 24 months, respectively. RESULTS: Eleven patients (8%) in the 3D-CRT group and 12 patients (8%) in the TPI group developed a biochemical relapse. The 5-year PSA relapse-free survival rates for the 3D-CRT and the TPI groups were 88% and 82%, respectively (P equals .09). Protracted grade 2 urinary symptoms were more prevalent among patients treated with TPI compared with 3D-CRT. Grade 2 urinary toxicity, which was manifest after the implant and persisted for more than 1 year after this procedure, was observed in 45 patients (31%) in the TPI group. In these 45 patients, the median duration of grade 2 urinary symptoms was 23 months (range, 12 to 70 months). On the other hand, acute grade 2 urinary symptoms resolved within 4 to 6 weeks after completion of 3D-CRT, and the 5-year actuarial likelihood of late grade 2 urinary toxicity for the 3D-CRT group was only 8%. The 5-year actuarial likelihood of developing a urethral stricture (grade 3 urinary toxicity) for the 3D-CRT and TPI groups was 2% and 12%, respectively (P less than .0002). Of 45 patients who developed grade 2 or higher urinary toxicity after TPI, the likelihood of resolution or significant improvement of these symptoms at 36 months from onset was 59%. The 5-year likelihood of grade 2 late rectal toxicity for the 3D-CRT and TPI patients was similar (6% and 11%, respectively; P equals .97). No patient in either group developed grade 3 or higher late rectal toxicity. The 5-year likelihood of posttreatment erectile dysfunction among patients who were initially potent before therapy was 43% for the 3D-CRT group and 53% for the TPI group (P equals .52). CONCLUSION: Both 3D-CRT and TPI are associated with an excellent PSA outcome for patients with early-stage prostate cancer. Urinary Toxicities are more prevalent for the TPI group and subsequently resolve or improve in most patients. In addition to evaluating long-term follow-up, future comparisons will require detailed quality-of-life assessments to further determine the impact of these toxicities on the overall well-being and quality of life of the individual patient. Editor's comments: The report by Zelefsky et al. adds to the growing body of data comparing the 5 year outcome and morbidity of 3DCRT to Transperineal I-125 implants for early prostate cancer. This analysis is based on an assessment of low risk patients treated either with 3DCRT or brachytherapy. Similar to the earlier report by D'Amico et al. (JAMA, 1998) these authors conclude that there was no difference in outcome for these low risk patients. Of note however, in this report the late GU complications were worse with the brachytherapy group. Also of note the incidence of impotence was similar contrary to the popular belief that brachytherapy provides higher potency rates. Taken together with the report by D 'Amico do these reports prove that there is no advantage to brachytherapy over 3D? In neither of these reports is the quality of brachytherapy accounted for. No systematic assessment of post implant dosimetry was reported in Dr. D'Amicos report and based on the description of their use of "MPD" it is doubtful that it was systematically done. More problematic is the fact that the implants at MSKCC were done under CT guidance (a practice since abandoned) and thus were probably not as good as TRUS directed implants. Furthermore, the outcomes were determined using the ASTRO consensus definition which may not be sensitive enough to detect true differences in outcome. Finally, Wallner et al. have also reported that in as many as 30% of patients there is a transient rise in the PSA between year 1 and 3 followed by a sustained decline. All of these patients would be counted as wrongly classified as treatment failures using the consensus definition. Zelefsky et al. are to be commended for sharing their experience with the radiotherapy community however until these issues are addressed in a more controlled setting the relative merits of these modalities remain to be determined. ****************** Radiobiology: Withers 5/99 AU: Huang SM, Bock JM, Harari PM. TI: Epidermal growth factor receptor blockade with C225 modulates proliferation, apoptosis, and radiosensitivity in squamous cell carcinomas of the head and neck. SO: Cancer Res 1999 Apr 15;59(8):1935-40. Abstract: We examined effects of the anti-epidermal growth factor receptor monoclonal antibody C225 on proliferation, cell cycle phase distribution, apoptosis, and radiosensitivity in squamous cell carcinoma (SCC) cell lines derived from head and neck cancer patients. Exposure to C225 in culture inhibits SCC proliferation in a time-dependent manner, and the degree of growth inhibition, compared to controls, ranges from 20 to 75%. Flow cytometry analysis demonstrates that C225 treatment induces accumulation of cells in G1, which is accompanied by a 2-3-fold decrease in the percentage of cells in S phase. C225 exposure also induces apoptosis in SCC populations, as demonstrated by flow cytometry analysis using dual stainings of merocyanine 540 and Hoechst 33342. Western blot analysis indicates that C225 exposure induces accumulation of hypophosphorylated retinoblastoma protein and increases expression of p27KIP1. An increase in Bax expression and concurrent decrease in Bcl-2 expression are observed when SCC cells are exposed to C225. Examination of C225 effects on radiation response in SCCs demonstrates enhancement in radiosensitivity and amplification of radiation-induced apoptosis. These effects are observed in both single-dose and fractionated radiation experiments. C225 represents a promising growth-inhibitory agent that can influence cellular proliferation, apoptosis, and radiosensitivity in SCCs of the head and neck. Editor's comments: This paper illustrates that when biological agents (in this case an antibody to the receptor for epidermal growth factor) are administered, there are several different pathways which may lead to an enhanced radiation response of tumor cells, even in vitro, which are not at first sight the target for the agent. Thus, the antibody may enhance apoptosis, increase intrinsic radiosensitivity and slow growth, and quite possibly other things as well. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC From daemon Fri May 7 14:02:57 1999 Received: (from daemon@localhost) by net.bio.net (8.9.1a/8.9.1) id OAA00423; Fri, 7 May 1999 14:02:57 -0700 (PDT) Message-Id: <199905072102.OAA00423@net.bio.net> To: radoncjc@net.bio.net Date: Fri, 7 May 1999 10:51:26 -1000 Reply-To: radoncjc@net.bio.net From: Brian J Goldsmith Subject: IROJC Lung 5/99 Lung 5/99 was erroneously omitted from the May 1999 IROJC posting. Below is the reference, abstract, and editor's comments. AU: Quon H; Shepherd FA; Payne DG; Coy P; Murray N; Feld R; Pater J; Sadura A; Zee B. TI: The influence of age on the delivery, tolerance, and efficacy of thoracic irradiation in the combined modality treatment of limited stage small cell lung cancer. SO: Int J Radiat Oncol Biol Phys 1999 Jan 1;43(1):39-45. Abstract: PURPOSE: To assess the impact of age on the delivery, tolerance, and efficacy of thoracic irradiation (TI) for limited small cell lung cancer (L-SCLC). METHODS AND MATERIALS: This is a retrospective review of data from 608 patients 80 years or less with L-SCLC, who participated in two previously reported randomized trials (BR3 and BR.6) of the National Cancer Institute of Canada. All patients received the same chemotherapy, consisting of cyclophosphamide, doxorubicin, vincristine (CAV), and etoposide cisplatin (EP) delivered either in sequential or alternating sequence. In BR.3, TI was given after chemotherapy with randomization to 25 Gy in 10 fractions or 37.5 Gy in 15 fractions. In BR.6, TI (40 Gy in 15 fractions) was given concurrently with EP with randomization to either the early (with cycle 2, week 4) or late (with cycle 6, week 16) arm. RESULTS: A total of 665 patients entered these two trials. Of these, 608 patients were eligible for analysis, 300 in BR.3 and 308 in BR.6. Five hundred and twenty patients were under age 70 and 88 patients were 70 years or older. Baseline characteristics between the two groups were comparable. In BR3, 179 patients (60%) participated in radiotherapy randomization (61% young, 52% elderly), and 176 patients actually received TI. In BR.6, randomization occurred at study entry for all patients, and 282 (91.6%) patients received TI (92% young, 88% elderly). More patients of both age groups randomized to receive late TI did not receive TI (13% and 14%) than those randomized to the early TI arm (3%) of BR.6. We could identify no tendency to reduce field sizes to minimize toxicity in either age group at higher doses of TI. Once TI was started, there was no difference between the two age groups with regards to the proportion of patients who completed TI, although elderly patients were less likely to complete high dose TI. Of those who completed TI, there was no difference in the time to complete TI, mean dose delivered or in the incidence of acute and late TI-related toxicities. No statistical difference in response rate, local relapse rate, or overall survival was seen between young and older age groups. CONCLUSION: In summary, in the dose range examined, age does not appear to impact on the delivery, tolerance or efficacy of TI in the combined modality management of L-SCLC. Potentially curative combined modality treatment should not be withheld on the basis of age. Editor's Comments: This study verifies my bias, so of course I like it. Patients well enough to enter trials usually have met certain screening criteria that make them perform like there mates in the cohorts, regardless of their age. Many studies formerly used the chronologic age as a barrier. This is no longer done in North America. The restriction for those with adequate performance status seems prudent. The use of age as a barrier to receive prophylactic cranial irradiation [PCI] also seems artifical. Many continue to worry that 'neurotoxicity' is a common event in small cell lung cancer patients provided with PCI. Many patients presenting with SCLC have neurocognitive deficits before therapy of any kind begins (see Komaki), but unlike the dissonant noise of the past two decades, when patients have been randomized to receive PCI or observation, there is not excess neurotoxicity in those receiving the PCI and followed. We do not know if there is age influence on this phenomenon, but I doubt it. The old are equally handicapped by brain relapses that occur in the majority of patients that do not receive PCI. Age should not be a barrier to receiving radiotherapy. The older set should not be denied the benefits of treatment because of their age. From daemon Fri May 7 14:23:22 1999 Received: by net.bio.net (8.9.1a/8.9.1) id OAA02723; Fri, 7 May 1999 14:23:22 -0700 (PDT) Message-Id: <199905072123.OAA02723@net.bio.net> To: radoncjc@net.bio.net Date: Fri, 7 May 1999 11:07:50 -1000 Reply-To: radoncjc@net.bio.net From: Brian J Goldsmith Subject: IROJC RES 5/99 RES 5/99 was erroneously omitted from the May 1999 IROJC posting. Below is the reference, abstract, editor comments. AU: Zinzani PL, Magagnoli M, Galieni P, Martelli M, Poletti V, Zaja F, Molica S, Zaccaria A, Cantonetti AC, Gentilini P, Guardigni L, Gherlinzoni F, Ribersani M, Bendandi M, Albertini P, Tura S. TI: Nongastrointestinal low-grade mucosa-associated lymphoid tissue lymphoma: analysis of 75 patients. SO: J Clin Oncol 17:1254-1258 URL: http://www.jco.org/abs17_4/v17n4p1254.html Abstract: PURPOSE: Nongastrointestinal locations represent about 30% to 40% of all low-grade mucosa-associated lymphoid tissue (MALT) lymphomas. We report a retrospective analysis of 75 patients with nongastrointestinal low-grade MALT lymphoma, presenting their clinical, therapeutic, and follow-up data with respect to the initial location of the lymphoma. PATIENTS AND METHODS: From January 1988 to October 1997, 75 patients with untreated nongastrointestinal low-grade MALT lymphoma were subjected to treatments ranging from local radiotherapy and local interferon alfa administration to chemotherapy. The lymphomas were located in the lung (19 patients), orbital soft tissue (16 patients), skin (seven patients), thyroid (seven patients), lachrymal gland (six patients), conjunctiva (six patients), salivary gland (six patients), breast (three patients), eyelid (two patients), larynx (one patient), bone marrow (one patient), and trachea (one patient). RESULTS: Complete and partial remissions were achieved in 59 (79%) and 16 (21%) of the 75 patients, respectively, with an overall response rate of 100%. All but two of the patients are still alive, with a median follow-up of 47 months; these two patients died from other causes. The estimated time to treatment failure rate is 30% at 5 years. In the thyroid and lachrymal gland sites, no relapses were reported. CONCLUSION: Our data regarding the largest reported series of nongastrointestinal MALT lymphomas confirm the good prognosis of this particular clinicopathologic entity and the significant efficacy of different therapeutic approaches to specific sites. Editor Comments: Although the epidemiology, natural history, and response to therapy of gastrointestinal MALT lymphomas has been well characterized (see IROJC RES selections for 11/95 and 6/98), the same is not the case for nongastrointestinal MALTS. These are relatively uncommon lymphomas that can arise in a number of sites. In this series of 75, most were in the lung (19/75) or orbit (16), skin (7) or thyroid (7). Most (63%) were stage IE-IIE. Treatments were variable. The key conclusion was that outcome was good for almost any therapy. At 5 years, the freedom-from-relapse was 70% and the survival was 95%.