From daemon Mon Mar 8 06:58:05 1999 Received: (from daemon@localhost) by net.bio.net (8.9.1a/8.9.1) id GAA07406; Mon, 8 Mar 1999 06:58:05 -0800 (PST) Message-Id: <199903081458.GAA07406@net.bio.net> To: radoncjc@net.bio.net Date: Mon, 8 Mar 1999 04:49:39 -1000 Reply-To: radoncjc@net.bio.net From: Brian J Goldsmith Subject: March 1999 Internet Radiation Oncology Journal Club (IROJC) March 1999 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 46th 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 3/99. (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. Example: comments submitted in March about a February IROJC reference will not be posted. (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 3/99 AU: Howrey RP, Lipham WJ, Schultz WH, Buckley EG, Dutton JJ, Klintworth GK, Rosoff PM. TI: Sebaceous gland carcinoma: a subtle second malignancy following radiation therapy in patients with bilateral retinoblastoma. SO: Cancer. 1998 Aug 15;83(4):767-71. URL: http://www.canceronline.wiley.com/ Abstract: BACKGROUND: Second primary malignancies are common after bilateral retinoblastoma; their estimated incidence has been as high as 51% 50 years after diagnosis. Fifteen patients who developed sebaceous gland carcinoma after radiation therapy have been reported in the literature, five of whom were treated for bilateral retinoblastoma. METHODS: The authors conducted a retrospective chart review of patients treated for bilateral retinoblastoma at Duke University Medical Center who later developed sebaceous gland carcinoma. RESULTS: This article reports two patients who developed sebaceous gland carcinoma after radiation therapy for bilateral retinoblastoma. CONCLUSIONS: Delay in diagnosis is often associated with sebaceous gland carcinoma. Because high mortality is observed with metastatic disease, the recognition of this association is important for anyone who follows patients with a history of bilateral retinoblastoma or prior cranial radiation therapy. Editor's comments: While Radiation Oncologists are acutely aware of the high frequency of second malignancies, particularly sarcomas, occuring in long term survivors of bilateral retinoblastoma, less attention has been placed on non-sarcomatous malignancies in this population. This article reports two cases of sebaceous gland carcinoma, a rare secondary malignancy, and serves as an excellent reminder of the importance of constant awareness of unusual tumors which can occur in patients with heritable retinoblastoma. ****************** Head/Neck/Skin: Foote 3/99 AU: Overgaard J, Hansen HS, Overgaard M, Bastholt L, Berthelsen A, Specht L, Lindelov B, Jorgensen K. TI: A randomized double-blind phase III study of nimorazole as a hypoxic radiosensitizer of primary radiotherapy in supraglottic larynx and pharynx carcinoma. Results of the Danish Head and Neck Cancer Study (DAHANCA) Protocol 5-85. SO: Radiother Oncol 1998 Feb;46(2):135-46. Abstract: PURPOSE: A multicenter randomized and balanced double-blind trial with the objective of assessing the efficacy and tolerance of nimorazole given as a hypoxic radiosensitizer in conjunction with primary radiotherapy of invasive carcinoma of the supraglottic larynx and pharynx. PATIENTS AND TREATMENT: Between January 1986 and September 1990, 422 patients (414 eligible) with pharynx and supraglottic larynx carcinoma were double-blind randomized to receive the hypoxic cell radiosensitizer nimorazole, or placebo, in association with conventional primary radiotherapy (62-68 Gy, 2 Gy per fraction, five fractions per week). The median observation time was 112 months. RESULTS: Univariate analysis showed that the outcome (5-year actuarial loco-regional tumor control) was significantly related to T-classification (T1-T2 48% versus T3-T4 36%, P equals 0.0008), neck-nodes (N- 53% versus N+ 33%), pre-irradiation hemoglobin (Hb) concentration (high 46% versus low 37%, P equals 0.02) and sex (females 51% versus males 38%, P equals 0.03). Overall the nimorazole group showed a significantly better loco-regional control rate than the placebo group (49 versus 33%, P equals 0.002). A similar significant benefit of nimorazole was observed for the end-points of final loco-regional control (including surgical salvage) and cancer-related deaths (52 versus 41%, P equals 0.002). This trend was also found in the overall survival but to a lesser, non-significant extent (26 versus 16%, 10-year actuarial values, P equals 0.32). Cox multivariate regression analysis showed the most important prognostic parameters for loco-regional control to be positive neck nodes (relative risk 1.84 (1.38-2.45)), T3-T4 tumor (relative risk 1.65 (1.25-2.17)) and nimorazole (relative risk 0.69 (0.52-0.90)). The same parameters were also significantly related to the probability of dying from cancer. The compliance to radiotherapy was good and 98% of the patients received the planned dose. Late radiation-related morbidity was observed in 10% of the patients, irrespective of nimorazole treatment. Drug-related side-effects were minor and tolerable with transient nausea and vomiting being the most frequent complications. CONCLUSION: Nimorazole significantly improves the effect of radiotherapeutic management of supraglottic and pharynx tumors and can be given without major side-effects. ****************** GYN: Grigsby 3/99 AU: Mitchell Morris, Patricia J. Eifel, Jiandong Lu, Perry W. Grigsby, Charles Levenback, Randy E. Stevens, Marvin Rotman, David M. Gershenson, David G. Mutch. TI: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. SO: N Engl J Med 1999 Apr 15; in press; full text available online (see URL). URL: http://www.nejm.org/content/morris/1.asp Abstract: BACKGROUND AND METHODS: We compared the effect of radiotherapy to a pelvic and para-aortic field with that of pelvic radiation and concurrent chemotherapy with fluorouracil and cisplatin in women with advanced cervical cancer. Between 1990 and 1997, 403 women with advanced cervical cancer confined to the pelvis (stages IIB through IVA or stage IB or IIa with a tumor diameter of at least 5 cm or involvement of pelvic lymph nodes) were randomly assigned to receive either 45 Gy of radiation to the pelvis and para-aortic lymph nodes or 45 Gy of radiation to the pelvis alone plus two cycles of fluorouracil and cisplatin (days 1 through 5 and days 22 through 26 of radiation). Patients were then to receive one or two applications of low-dose-rate intracavitary radiation, with a third cycle of chemotherapy planned for the second intracavitary procedure in the combined-therapy group. RESULTS: Of the 403 eligible patients, 193 in each group could be evaluated. The median duration of follow-up was 43 months. Estimated cumulative rates of survival at five years were 73 percent among patients treated with radiotherapy and chemotherapy and 58 percent among patients treated with radiotherapy alone (P equals 0.004). Cumulative rates of disease-free survival at five years were 67 percent among patients in the combined-therapy group and 40 percent among patients in the radiotherapy group (P less than 0.001). The rates of both distant metastases (P less than 0.001) and locoregional recurrences (P less than 0.001) were significantly higher among patients treated with radiotherapy alone. The seriousness of side effects was similar in the two groups, with a higher rate of reversible hematologic effects in the combined-therapy group. CONCLUSIONS: The addition of chemotherapy with fluorouracil and cisplatin to treatment with external-beam and intracavitary radiation significantly improved survival among women with locally advanced cervical cancer. AU: Peter G. Rose, Brian N. Bundy, Edwin B. Watkins, J. Tate Thigpen, Gunther Deppe, Mitchell A. Maiman, Daniel L. Clarke-Pearson, Sam Insalaco. TI: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. SO: N Engl J Med 1999 Apr 15; in press; full text available online (see URL). URL: http://www.nejm.org/content/rose/1.asp Abstract: BACKGROUND AND METHODS: On behalf of the Gynecologic Oncology Group, we performed a randomized trial of radiotherapy in combination with three concurrent chemotherapy regimens -- cisplatin alone; cisplatin, fluorouracil, and hydroxyurea; and hydroxyurea alone -- in patients with locally advanced cervical cancer. Women with primary untreated invasive squamous-cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix of stage IIB, III, or IVA, without involvement of the para-aortic lymph nodes, were enrolled. The patients had to have a leukocyte count of at least 3000 per cubic millimeter, a platelet count of at least 100,000 per cubic millimeter, a serum creatinine level no higher than 2 mg per deciliter (177 mol per liter), and adequate hepatic function. All patients received external-beam radiotherapy according to a strict protocol. Patients were randomly assigned to receive one of three chemotherapy regimens: 40 mg of cisplatin per square meter of body-surface area per week for six weeks (group 1); 50 mg of cisplatin per square meter on days 1 and 29, followed by 4 g of fluorouracil per square meter given as a 96-hour infusion on days 1 and 29, and 2 g of oral hydroxyurea per square meter twice weekly for six weeks (group 2); or 3 g of oral hydroxyurea per square meter twice weekly for six weeks (group 3). RESULTS: The analysis included 526 women. The median duration of follow-up was 35 months. Both groups that received cisplatin had higher rate of progression-free survival than the group that received hydroxyurea alone (P less than 0.001 for both comparisons). The relative risks of progression of disease or death were 0.57 (95 percent confidence interval, 0.42 to 0.78) in group 1 and 0.55 (95 percent confidence interval, 0.40 to 0.75) in group 2, as compared with group 3. The overall survival rate was significantly higher in groups 1 and 2 than in group 3, with relative risks of death of 0.61 (95 percent confidence interval, 0.44 to 0.85) and 0.58 (95 percent confidence interval, 0.41 to 0.81), respectively. CONCLUSIONS: Regimens of radiotherapy and chemotherapy that contain cisplatin improve the rates of survival and progression-free survival among women with locally advanced cervical cancer. AU: Henry M. Keys, Brian N. Bundy, Frederick B. Stehman, Laila I. Muderspach, Weldon E. Chafe, Charles L. Suggs III, Joan L. Walker, Deborah Gersell. TI: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage Ib cervical carcinoma. SO: N Engl J Med 1999 Apr 15; in press; full text available online (see URL). URL: http://www.nejm.org/content/keys/1.asp Abstract: BACKGROUND: Bulky stage IB cervical cancers have a poorer prognosis than smaller stage I cervical cancers. For the Gynecologic Oncology Group, we conducted a trial to determine whether weekly infusions of cisplatin during radiotherapy improve progression-free and overall survival among patients with bulky stage IB cervical cancer. METHODS: Women with bulky stage IB cervical cancers (tumor, greater than or equal to 4 cm in diameter) were randomly assigned to receive radiotherapy alone or in combination with cisplatin (40 mg per square meter of body-surface area once a week for up to six doses; maximal weekly dose, 70 mg), followed in all patients by adjuvant hysterectomy. Women with evidence of lymphadenopathy on computed tomographic scanning or lymphangiography were ineligible unless histologic analysis showed that there was no lymph-node involvement. The cumulative dose of external pelvic and intracavitary radiation was 75 Gy to point A (cervical parametrium) and 55 Gy to point B (pelvic wall). Cisplatin was given during external radiotherapy, and adjuvant hysterectomy was performed three to six weeks later. RESULTS: The relative risks of progression of disease and death among the 183 women assigned to receive radiotherapy and chemotherapy with cisplatin, as compared with the 186 women assigned to receive radiotherapy alone, were 0.51 (95 percent confidence interval, 0.34 to 0.75) and 0.54 (95 percent confidence interval, 0.34 to 0.86), respectively. The rates of both progression-free survival (P less than 0.001) and overall survival (P equals 0.008) were significantly higher in the combined-therapy group at four years. In the combined-therapy group there were higher frequencies of transient grade 3 (moderate) and grade 4 (severe) adverse hematologic effects (21 percent, vs. 2 percent in the radiotherapy group) and adverse gastrointestinal effects (14 percent vs. 5 percent). CONCLUSIONS: Adding weekly infusions of cisplatin to pelvic radiotherapy followed by hysterectomy significantly reduced the risk of disease recurrence and death in women with bulky stage IB cervical cancers. ****************** GI / Soft Tissue Sarcoma: Tepper 3/99 No Reference Selected ****************** CNS: Larson 3/99 AU: Kondziolka D, Lunsford LD, McLaughlin MR, Flickinger JC. TI: Long-term outcomes after radiosurgery for acoustic neuromas. SO: N Engl J Med 1998 Nov 12;339(20):1426-33 URL: http://www.nejm.org/content/1998/0339/0020/1426.asp Abstract: BACKGROUND: Stereotactic radiosurgery is the principal alternative to microsurgical resection for acoustic neuromas (vestibular schwannomas). The goals of radiosurgery are the long-term prevention of tumor growth, maintenance of neurologic function, and prevention of new neurologic deficits. Although acceptable short-term outcomes have been reported, long-term outcomes have not been well documented. METHODS: We evaluated 162 consecutive patients who underwent radiosurgery for acoustic neuromas between 1987 and 1992 by means of serial imaging tests, clinical evaluations, and a survey between 5 and 10 years after the procedure. The average dose of radiation to the tumor margin was 16 Gy, and the mean transverse diameter of the tumor was 22 mm (range, 8 to 39). Resection had been performed previously in 42 patients (26 percent); in 13 patients the tumor represented a recurrence of disease after a previous total resection. Facial function was normal in 76 percent of the patients before radiosurgery, and 20 percent had useful hearing. RESULTS: The rate of tumor control (with no resection required) was 98 percent. One hundred tumors (62 percent) became smaller, 53 (33 percent) remained unchanged in size, and 9 (6 percent) became slightly larger. Resection was performed in four patients (2 percent) within four years after radiosurgery. Normal facial function was preserved in 79 percent of the patients after five years (House-Brackmann grade 1), and normal trigeminal function was preserved in 73 percent. Fifty-one percent of the patients had no change in hearing ability. No new neurologic deficits appeared more than 28 months after radiosurgery. An outcomes questionnaire was returned by 115 patients (77 percent of the 149 patients still living). Fifty-four of these patients (47 percent) were employed at the time of radiosurgery, and 37 (69 percent) remained so. Radiosurgery was believed to have been successful by all 30 patients who had undergone surgery previously and by 81 (95 percent) of the 85 who had not. Thirty-six of the 115 patients (31 percent) described at least one complication, which resolved in 56 percent of those cases. CONCLUSIONS: Radiosurgery can provide long-term control of acoustic neuromas while preserving neurologic function. ****************** Physics/Dosimetry: Purdy 3/99 No Reference Selected ****************** Breast: Recht 3/99 AU: Olivotto IA, Jackson JS, Mates D, Andersen S, Davidson W, Bryce CJ, Ragaz J. TI: Prediction of axillary lymph node involvement of women with invasive breast carcinoma: a multivariate analysis. SO: Cancer 1998 Sep 1;83(5):948-55. URL: http://www.canceronline.wiley.com/ Abstract: BACKGROUND: The increasing use of systemic therapy for women with lymph node negative breast carcinoma and earlier stage of disease at mammographic detection raises questions regarding the need for routine axillary lymph node dissection. Predictive modeling for lymph node involvement may be one way to reduce the need for axillary lymph node dissection and its morbidity. METHODS: A multivariate analysis of 12 factors predictive of axillary lymph node involvement was conducted in a population-based cohort of 4312 women with invasive breast carcinoma diagnosed between January 1, 1993 and December 31, 1996. RESULTS: Clinical palpability, lymphatic or vascular invasion, lesion size, margin status, histology, and patient age were independent predictors of axillary lymph node involvement. The model correctly identified lymph node status in 76.6% of cases. Model accuracy and fit were equally high when applied to randomly selected halves of the study subjects. Approximately 32.0% of the patients in the study sample (1363/4312) were identified as having an extremely high (91%; n equals 1102) or low (10%; n equals 261) risk of lymph node involvement. In a second analysis, a clinically useable, three-variable model identified a very low risk group of patients (n equals 147) with a 4.8% risk of lymph node metastasis and a high risk group of patients (n equals 1008) with a 74.2% risk of lymph node metastasis. Greater than 90% of subjects in the high risk group received adjuvant systemic therapy even if they were lymph node negative pathologically. CONCLUSIONS: A clinically useable, three-variable model employing tumor and lymph node palpability, size, and lymphatic or vascular invasion can identify women with invasive breast carcinoma in whom axillary lymph node dissection is very unlikely to alter recommendations regarding adjuvant systemic therapy. Editor's comments: This is perhaps the single best article of its kind I know of looking at whether the risk of axillary node involvement can be predicted using characteristics of the patient and primary tumor. The authors were able to identify a group of patients with a 5% risk of node involvement (nonpalpaple primary tumors which were 0.5 cm diameter or smaller without lymphatic or blood vessel invasion) - which group however constituted only 3.4% of their very large population-based cohort. The risk of having 4 or more positive nodes in this group was only 1.4%. Similarly, they identified in whom 74% of patients had positive nodes (clinically palpable nodes present in patients with palpable tumors 2cm or larger with lymphatic or vascular invasion); and about one-third of the node-positive patients in this group had 4 or more positive nodes. This group made up about 23% of their study population. The authors note that over 90% of even the node-negative patients in this "highest-risk" group received systemic therapy, based on their then-existing protocols. However, the risk of nodal involvement in the two intermediate risk groups they identified were 12% and 28%; the risk of having 4 or more positive nodes was substantially lower (1.8% and 5%, respectively). The two questions (which are beyond the scope of this article) that then need to be addressed to assess the clinical implications of such findings (i.e., whether surgical axillary staging should be performed). First, will knowledge of the presence or number of involved nodes make a difference in whether systemic therapy is given or, more often perhaps, what kind of systemic therapy is given? (This question involves considering not just treatment effectiveness but toxicities.) Second, what is the minimum difference in outcome (for an individual or a society) that would justify putting patients through such staging, knowing that such changes in management as are made are likely to have small impacts on the outcome of the population as a whole - but perhaps substantial ones for some individuals? (More crassly: does the pain of the many justify the gain of a few?) I predict that articles like the present one will help speed the evolution of breast cancer treatment in the same direction as for Hodgkin's disease - less reliance on surgical staging as everyone becomes more "comfortable" with clinical prognostic systems and the routine use of systemic therapy. ****************** RES: Hoppe 3/99 No Reference Selected ****************** Lung/Mediastinum: Turrisi 3/99 No Reference Selected ****************** GU: Roach 3/99 AU: Dearnaley DP, Khoo VS, Norman AR, Meyer L, Nahum A, Tait D, Yarnold J, Horwich A. TI: Comparison of radiation side-effects of conformal and conventional radiotherapy in prostate cancer: a randomised trial. SO: Lancet 1999 Jan 23;353(9149):267-72. URL: http://www.thelancet.com/ Abstract: BACKGROUND: Radical radiotherapy is commonly used to treat localised prostate cancer. Late chronic side-effects limit the dose that can be given, and may be linked to the volume of normal tissues irradiated. Conformal radiotherapy allows a smaller amount of rectum and bladder to be treated, by shaping the high-dose volume to the prostate. We assessed the ability of this new technology to lessen the risk of radiation-related effects in a randomised controlled trial of conformal versus conventional radiotherapy. METHODS: We recruited men with prostate cancer for treatment with a standard dose of 64 Gy in daily 2 Gy fractions. The men were randomly assigned conformal or conventional radiotherapy treatment. The primary endpoint was the development of late radiation complications (greater than 3 months after treatment) measured with the Radiation Therapy and Oncology Group (RTOG) score. Indicators of disease (cancer) control were also recorded. FINDINGS: In the 225 men treated, significantly fewer men developed radiation-induced proctitis and bleeding in the conformal group than in the conventional group (37 vs 56% greater than or equal to RTOG grade 1, p equals 0.004; 5 vs 15% greater than or equal to RTOG grade 2, p equals 0.01). There were no differences between groups in bladder function after treatment (53 vs 59% greater than or equal to grade 1, p equals 0.34; 20 vs 23% greater than or equal to grade 2, p equals 0.61). After median follow-up of 3.6 years there was no significant difference between groups in local tumour control (conformal 78% [95% CI 66-86], conventional 83% [69-90]). INTERPRETATION: Conformal techniques significantly lowered the risk of late radiation-induced proctitis after radiotherapy for prostate cancer. Widespread introduction of these radiotherapy treatment methods is appropriate. Our results are the basis for dose-escalation studies to improve local tumour control. Editor's comments: The recent report by Dearnaley et al. provides additional support for the assertion that 3D conformal radiotherapy is better than conventional radiotherapy when treating prostate cancer (Dearnaley 1999). The report from the Royal Marsden demonstrated that although the acute toxicity was unchanged the late effects were reduced when patients were treated using 3D planning compared to conventional radiotherapy. This is the second prospective randomized trial that has shown that the late effects of radiotherapy for prostate cancer are reduced with the use of 3DCRT compared to conventional therapy (Nguyen 1998). Last year investigators from MD Anderson also demonstrated that the use of 3D conformal technology reduced late complications even when higher doses of radiation were used. These two studies combined with the various retrospective studies that suggests that there is a dose response, strongly argue that all patients being treated for prostate cancer with radiation should be treated using 3D. There is also reason for further optimism. The use of Intensity Modulated Radiotherapy (IMRT) should allow us to "raise the bar" even further toward reduced complications. To this end the NCI has formed a IMRT working group that will define the standard "jargon" for the next generation of 3D, IMRT. Mack Roach III MD 1 Dearnaley, D. P., Khoo, V.S., Norman, A., Meyer, L., Nahum, A., Tait, D., Horwich, A. (1999). "Comparison of radiation side-effects conformal and conventional radiotherapy in prostate cancer: a randomized trial." Lancet 353:267-72. 2 Nguyen, L. N., Pollack, A., Zagars, G.K. (1998). "Late Effects after radiotherapy for prostate cancer in a randomized dose-response study: results of a self-assessment." Urology 51(6): 991-997. ****************** Radiobiology: Withers 3/99 No Reference Selected ****************** Brian J. Goldsmith, M.D. Moderator, IROJC From daemon Mon Mar 8 13:51:18 1999 Received: by net.bio.net (8.9.1a/8.9.1) id NAA23642; Mon, 8 Mar 1999 13:51:18 -0800 (PST) Message-Id: <199903082151.NAA23642@net.bio.net> To: radoncjc@net.bio.net Date: Mon, 8 Mar 1999 11:43:52 -1000 Reply-To: radoncjc@net.bio.net From: Brian J Goldsmith Subject: IROJC Lung 3/99 Lung 3/99 was erroneously omitted from the March 1999 IROJC posting. Below is the reference, abstract, moderator question, and editor reply. AU: Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. TI: Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. SO: N Engl J Med 1999 Jan 28;340(4):265-71. URL: http://www.nejm.org/content/1999/0340/0004/0265.asp Abstract: BACKGROUND: For small-cell lung cancer confined to one hemithorax (limited small-cell lung cancer), thoracic radiotherapy improves survival, but the best ways of integrating chemotherapy and thoracic radiotherapy remain unsettled. Twice-daily accelerated thoracic radiotherapy has potential advantages over once-daily radiotherapy. METHODS: We studied 417 patients with limited small-cell lung cancer. All the patients received four 21-day cycles of cisplatin plus etoposide. We randomly assigned these patients to receive a total of 45 Gy of concurrent thoracic radiotherapy, given either twice daily over a three-week period or once daily over a period of five weeks. RESULTS: Twice-daily treatment beginning with the first cycle of chemotherapy significantly improved survival as compared with concurrent once-daily radiotherapy (P equals 0.04 by the log-rank test). After a median follow-up of almost 8 years, the median survival was 19 months for the once-daily group and 23 months for the twice-daily group. The survival rates for patients receiving once-daily radiotherapy were 41 percent at two years and 16 percent at five years. For patients receiving twice-daily radiotherapy, the survival rates were 47 percent at two years and 26 percent at five years. Grade 3 esophagitis was significantly more frequent with twice-daily thoracic radiotherapy, occurring in 27 percent of patients, as compared with 11 percent in the once-daily group (P less than 0.001). CONCLUSIONS: Four cycles of cisplatin plus etoposide and a course of radiotherapy (45 Gy, given either once or twice daily) beginning with cycle 1 of the chemotherapy resulted in overall two- and five-year survival rates of 44 percent and 23 percent, a considerable improvement in survival rates over previous results in patients with limited small-cell lung cancer. Moderator Question: Did you go APPA to 30Gy, then off-cord for 15Gy, or did you interdigitate the APPA and obliques in an AM/PM alternating fashion? I think I remember reading about a 1.5Gy APPA bid to 15Gy, then 1.5Gy APPA qAM / 1.5Gy oblique qPM for the last 30Gy technique. The NEJM article wasn't specific about this point. Editor's Reply: We allowed the cord 36 Gy, and initially suggested obliques for PM sessions of weeks 2 and 3 -- this was the original way. The CHART people now doing CHARTWEL, weekend-less, are allowing more than 40 Gy despite one case or so of myelopathy at 37.5 with real CHART. I'd bet 45 Gy is tolerable, but would also bet that smaller volumes and lower cord doses are possible with three-D. The interval was min 6 hrs by the way. From daemon Tue Mar 9 11:27:46 1999 Received: by net.bio.net (8.9.1a/8.9.1) id LAA27451; Tue, 9 Mar 1999 11:27:46 -0800 (PST) Message-Id: <199903091927.LAA27451@net.bio.net> To: radoncjc@net.bio.net Date: Tue, 09 Mar 1999 12:26:48 +1000 Reply-To: radoncjc@net.bio.net From: "Duchesne, Gillian" Subject: Lung 3/99 It would be interesting to know if there was any notable difference in late pulmonary toxicity between the two arms. Although the increase in control probably relates to the accelerated nature of the experimental arm, it might be expected that the smaller fraction size could still spare late toxicity. Any data? Assoc Prof Gillian Duchesne Radiation Oncology Peter MacCallum Cancer Institute Locked Bag 1, A Beckett St Melbourne 8006, Victoria, Australia Tel: 61-3-9656-1111 Fax: 61-3-9656-1424 From daemon Thu Mar 25 12:27:04 1999 Received: by net.bio.net (8.9.1a/8.9.1) id MAA27754; Thu, 25 Mar 1999 12:27:04 -0800 (PST) Message-Id: <199903252027.MAA27754@net.bio.net> To: radoncjc@net.bio.net Date: Tue, 9 Mar 1999 16:34:54 -0500 Reply-To: radoncjc@net.bio.net From: "Andrew Turrisi M.D." Subject: RE: Lung 3/99 Of 417 entrant, only 8 pulmonary events of any kind. I think the BID arm had one death - - very bad treatment plan too. The real issue with pulmonary toxicity is finding a marker that reports injury before pneumonitis or fibrosis. Thanks for the question. Drew Turrisi