From daemon Sun Dec 1 05:59:31 1996 Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id FAA19766 Message-Id: <199612011359.FAA19766@net.bio.net> To: radoncjc@net.bio.net Date: Sun, 1 Dec 1996 03:41:43 -1000 Reply-To: radoncjc@net.bio.net From: bjg@littleb.mhpcc.edu (Brian Goldsmith) Subject: December 1996 Internet Radiation Oncology Journal Club (IROJC) December 1996 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 19th collection of references suggested for attention and discussion by the IROJC's Board of Editors: Sarah Donaldson, M.D. Editor, Pediatric Radiation Oncology Bill Mendenhall, 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 James Cox, M.D. Editor, Lung and Mediastinum Radiation Oncology Joel Tepper, M.D. Editor, Gastrointestinal 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 are 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 the professional ground rules listed 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/ Using your web browser, click on the "Access the BIOSCI/bionet Newsgroups" hyperlink, and then go to the "RADIATION-ONCOLOGY/Prototype" folder. Or you can directly access the RADIATION-ONCOLOGY folder at http://www.bio.net:80/hypermail/RADIATION-ONCOLOGY/ The IROJC webpage also has a freeWAIS search tool, which enables the reader to search archived postings for keywords or phrases! ------------------------------------------------------------ Commentary Ground Rules: Please, (1) Cite the subject category in the header of your e-mail message, e.g. Subject: Peds 12/96. (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) Recognize that the Editor's selection is not necessarily an endorsement of the authors' conclusions. In fact, articles may be selected for criticism. (4) Be aware that your comments, once 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 December about a November 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 (hawaiirt@aol.com) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 12/96 AU: Kuttesch JF, Wexler LH, Marcus RB, Fairclough D, Weaver-McClure L, White M, Mao L, Delaney TF, Pratt CB, Horowitz ME, Kun LE. TI: Second malignancies after Ewing's sarcoma: radiation dose-dependency of secondary sarcomas. SO: J Clin Oncol 14:2818-2825, 1996. Abstract: BACKGROUND: An excess risk of second malignancies has been reported in survivors of Ewing's sarcoma. We examined a multiinstitutional data base to reevaluate the risk among survivors of Ewing's sarcoma and to identify possible causal factors. METHODS: Information was derived from a data base that included 266 survivors of Ewing's sarcoma. Cumulative incidence rates of second malignancies were calculated. Contributions of clinical features, type and dose of chemotherapy, and cumulative radiation dose to the risk of second malignancies were evaluated. RESULTS: After a median follow-up duration of 9.5 years (range, 3.0 to 30), 16 patients have developed second malignancies, which included 10 sarcomas (five osteosarcomas, three fibrosarcomas, and two malignant fibrous histiocytomas) and six other malignancies (acute myeloblastic leukemia, acute lymphoblastic leukemia, meningioma, bronchioalveolar carcinoma, basal cell carcinoma, and carcinoma-in-situ of the cervix). The median latency to the diagnosis of the second malignancy was 7.6 years (range, 3.5 to 25.7). The estimated cumulative incidence rates at 20 years for any second malignancy and for secondary sarcoma were 9.2% (SD = 2.7%) and 6.5% (SD = 2.4%), respectively. The cumulative incidence rate of secondary sarcoma was radiation dose-dependent (P = .002). No secondary sarcomas developed among patients who had received less than 48 Gy, while the absolute risk of secondary sarcoma was 130 cases per 10,000 person-years of observation among patients who had received 60 Gy or more. CONCLUSION: The overall risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose-dependency of secondary sarcomas justifies modification in therapy to reduce radiation doses. Editor's comments: Currently there is great concern, perhaps excessive concern, on the part of Orthopedic Oncologists and in some respects Pediatric Oncologists, regarding a high risk of secondary malignancies among patients treated with irradiation and chemotherapy successfully for Ewings Sarcoma. Because of this more and more attention is being given to preforming operative procedures designed for Osteogenic Sarcoma patients in combination with chemotherapy, in an attempt to "avoid irradiation". This paper by Kuttesch et al is an important one, as it clarifies that the risk of second malignancies after Ewing's sarcomas is similar to that associated with treatment for other childhood cancers. The radiation dose administered is important, and radiation oncologists today need to be familiar with this paper and the literature on this subject so to design radiation treatment plans appropriately. It is not necessary that all patients with Ewings Sarcoma receive a surgical resection as part of the "Local Control" treatment. ****************** Head/Neck/Skin: Mendenhall 12/96 No Reference Selected. ****************** GYN: Grigsby 12/96 AU: Virostek LJ, Kim RY, Spencer SA, Meredith RF, Jennelle RLS, Soong SJ, Salter MM. TI: Postsurgical recurrent carcinoma of the cervix: reassessment and results of radiation therapy options. SO: Radiology 1996; 201:559-563. Abstract: PURPOSE: To evaluate outcome and reassess the radiation therapy options in pelvic recurrences of cervical cancer treated initially with surgery. MATERIALS AND METHODS: In 30 patients, the prognostic factors analyzed for local control included site of recurrence (central, pelvic wall), tumor size, modality of radiation therapy, and radiation dose. Mean follow-up in survivors was 111.5 months. RESULTS: Local control was attained in (a) nine of 20 patients with central recurrence and in two of 10 with pelvic wall recurrence (P = .25); (b) none of four who received less than 50 Gy, five of nine who received 50-60 Gy, and six of 17 who received greater than 60 Gy (P = .27); and (c) five of 11 with tumor smaller than 3 cm, five of nine with tumor size 3-6 cm, and one of 10 with tumor larger than 6 cm. Multivariate analysis revealed a significant benefit of local control on survival (P = .05). Median survival for patients with central recurrence was 14.5 months compared with 9 months for those with pelvic wall recurrence. CONCLUSION: Local pelvic control depends on site and size of recurrence and radiation therapy modality and dose. Appropriate choice of brachytherapy modality is important. To improve local control and survival, more aggressive treatment is indicated, but attendant higher complications may be expected. ****************** GI: Tepper 12/96 No Reference Selected. ****************** CNS: Larson 12/96 AU: Flickinger JC, Kondziolka D, Pollock BE, Lunsford LD. TI: Evolution in technique for vestibular schwannoma radiosurgery and effect on outcome. SO: Int J Radiat Oncol Biol Phys 36:275-280, 1996. Abstract: PURPOSE: To define changes in treatment technique for vestibular schwannoma radiosurgery and to relate them to changes in outcome, a large single institution experience was reviewed. METHODS AND MATERIALS: Two hundred seventy-three patients with unilateral vestibular schwannoma underwent Gamma knife radiosurgery: 118 with computed tomography (CT) treatment planning during 1987-1991, and 155 with magnetic resonance imaging (MR) treatment planning in 1991-1994. Mean treatment parameters differed between the CT and MR groups: minimum tumor dose (Dmin) was 17 vs. 14 Gy, number of isocenters was 3.4 vs 5.8 and volume was 3.5 vs. 2.7 cc., respectively. RESULTS: The actuarial 7-year clinical tumor control rate (no requirement for surgical intervention) for the entire series was 96.4+/-2.3%, with a radiographic tumor control rate of 91.0+/-3.4%; these rates were similar for the CT and MR groups. Significantly lower rates of post radiosurgery facial, trigeminal and auditory neuropathy were observed in the MR group compared to the CT group. Multivariate analyses found significant independent correlations of increasing rates of facial and trigeminal neuropathy with increasing transverse tumor diameter and Dmins as well as with CT treatment planning (compared to MR). Decreased hearing was similarly correlated with diameter and CT planning but not with Dmin. CONCLUSIONS: Changes in radiosurgery technique and the use of lower doses improved the outcome after vestibular schwannoma radiosurgery by decreasing cranial neuropathy rates. MR-based treatment planning appears to have significantly contributed to this improvement. Despite decrease in radiation dose, no change in the high rate of tumor control has yet been observed. ****************** Physics/Dosimetry: Purdy 12/96 AU: Kalet IJ, Jacky JP, Austin-Seymour MM, Hummel SM, Sullivan KJ, and Unger JM. TI: Prism: a new approach to radiotherapy planning software. SO: Int J Radiat Oncol Biol Phys 36:451-461; 1996. Abstract: PURPOSE: We describe the capabilities and performance of Prism, an innovative new radiotherapy planning system with unusual features and design. The design and implementation strategies are intended to assure high quality and clinical acceptability. The features include Artificial Intelligence tools and special support for multileaf collimator (MLC) systems. The design provides unusual flexibility of operation and ease of expansion. METHODS AND MATERIALS: We have implemented Prism, a three dimensional (3D) radiotherapy treatment-planning system on standard commercial work stations with the widely available X window system. The design and implementation use ideas taken from recent software engineering research, for example, the use of behavioral entity-relationship modeling and the "Mediator Method" instead of ad-hoc programming. The Prism system includes the usual features of a 3D planning system, including Beam's Eye View and the ability to simulate any treatment geometry possible with any standard radiotherapy accelerator. It includes a rule-based expert system for automated generation of the planning target volume as defined in ICRU Report 50. In addition, it provides special support for planning treatments with a multileaf collimator (MLC). We also implemented a Radiotherapy Treatment Planning Tools Foundation for Prism, so that we are able to use software tools from other institutions without any source code modification. RESULTS: The Prism system has been in clinical operation at the University of Washington since July 1994 and has been installed at several other clinics. The system is run simultaneously by several users, each with their own work station operating from a common networked data base and software . In addition to the dosimetrists, the system is used by radiation oncologist to define tumor and target volumes and by radiation therapists to select treatment setups to load into a computer controlled accelerator. CONCLUSIONS: Experience with the installation and operation has shown the design to be effective as both a clinical and research tool. Integration of software tools has eased the development and significantly enhanced the clinical usability of the system. The design has been shown to be a sound basis for further innovation in radiation treatment planning software and for research in the treatment planning process. ****************** Breast: Recht 12/96 AU: Early Breast Cancer Trialists' Collaborative Group. TI: Ovarian ablation in early breast cancer: overview of the randomized trials. SO: Lancet 1996; 348:1189-96. Abstract: BACKGROUND: Among women with early breast cancer, the effects of ovarian ablation on recurrence and death have been assessed by several randomised trials that now have long follow-up. In this report, the Early Breast Cancer Trialists' Collaborative Group present their third 5-yearly systematic overview (meta-analysis), now with 15 years' follow-up. METHODS: In 1995, information was sought on each patient in any randomised trial of ovarian ablation or suppression versus control that began before 1990. Data were obtained for 12 of the 13 studies that assessed ovarian ablation by irradiation or surgery, all of which began before 1980, but not for the four studies that assessed ovarian suppression by drugs, all of which began after 1985. Menopausal status was not consistently defined across trials; therefore, the main analyses are limited to women aged under 50 (rather than "premenopausal") when randomised. Oestrogen receptors were measured only in the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone. FINDINGS: Among 2102 women aged under 50 when randomised, most of whom would have been pre-menopausal at diagnosis, 1130 deaths and an additional 153 recurrences were reported. 15-year survival was highly significantly improved among those allocated ovarian ablation (52.4 vs 46.1%, 6.3 [SD 2.3] fewer deaths per 100 women, logrank 2p=0. 001), as was recurrence-free survival (45.0 vs 39.0%, 2p=0.0007). The numbers of events were too small for any subgroup analyses to be reliable. The benefit was, however, significant both for those with ("node positive") and for those without ("node negative") axillary spread when diagnosed. In the trials of ablation plus cytotoxic chemotherapy versus the same chemotherapy alone, the benefit appeared smaller (even for women with oestrogen receptors detected on the primary tumour) than in the trials of ablation in the absence of chemotherapy (where the observed survival improvements were about six per 100 node-negative women and 12 per 100 node-positive women). Among 1354 women aged 50 or over when randomised, most of whom would have been perimenopausal or postmenopausal, there was only a non-significant improvement in survival and recurrence-free survival. INTERPRETATION: In women aged under 50 with early breast cancer, ablation of functioning ovaries significantly improves long-term survival, at least in the absence of chemotherapy. Further randomised evidence is needed on the additional effects of ovarian ablation in the presence of other adjuvant treatments, and to assess the relevance of hormone-receptor measurements. Editor's Comments: This is the latest publication in this continuing project. Like others in this series, the heterogeneity of the patient populations, staging, and treatments between the different studies means that the subgroup analyses are much more important for current practitioners than are the global analyses. For example, the effect of ovarian ablation is impressive in women under 50 who did not receive chemotherapy, but much less so when chemotherapy was also given. Nearly (but not quite) all node-negative patients were in trials randomizing patients to observation or ovarian ablation, while most (but not all) node-positive patients were in trials randomizing patients between chemotherapy or chemotherapy plus ablation. While the results are divided according to nodal status for patients in trials comparing ovarian ablation to observation (Figure 3), this was not done for the trials comparing chemotherapy to chemotherapy plus ablation. This means that the results of the analysis of these trials (Figure 2) may be an inaccurate reflection of the results of adding ablation to chemotherapy in nodal subgroups. The picture with respect to estrogen receptor status is also limited, as this assay was routinely performed only in 4 trials comparing chemotherapy to ablation plus chemotherapy (p. 1193). Hence, many questions of clinical relevance remain unanswered by this analysis. I also wish to note a letter to the editor (Givens SS, IJROBP 1996;36:525) commenting on the article picked for the June 1996 Journal Club (Fein et al, IJROBP 1996;34:1009-17) regarding the value of surgical clips. Dr. Givens points out that one reason clips may not have mattered is that CT planning was used to locate the biopsy cavity in all patients, so that whether clips were placed or not, the boost could be accurately placed. While this may be one explanation for their findings, it is worth noting that in a series from the JCRT in which clips and CT localization were not used, the risk of recurrence at 5 years was 2% in all patients with negative margins (Gage et al, Cancer 1996;78:1921-8). Hence, it seems likely that margin status is more important, as Fein and Fowble suggest in their response (although they still advocate the placement of clips). ****************** RES: Hoppe 12/96 AU: Bolek TW; Marcus RB; Mendenhall NP. TI: Solitary plasmacytoma of bone and soft tissue. SO: Int J Radiat Oncol Biol Phys 1996; 36:329-333. Abstract: PURPOSE: This retrospective review evaluates the results of radiotherapy used for curative intent in the management of solitary plasmacytoma. METHODS AND MATERIALS: Between August 1963 and January 1993, 37 patients with a solitary plasmacytoma were treated with curative intent at the University of Florida. Criteria for inclusion in the study were (a) a biopsy proven plasmacytoma, (b) no tumor in the bone marrow on biopsy, and (c) no evidence of disseminated disease on skeletal survey. The primary site was osseous in 27 patients and extramedullary in 10 patients; 9 of the 10 extramedullary lesions were located in the upper respiratory passages. Treatment consisted of primary radiotherapy in all but one patient, who received surgical resection alone. Two patients also received adjuvant chemotherapy. The median radiation dose was 43.2 Gy in 1.8-Gy fractions. Absolute survival, progression to myeloma, and local control rates were calculated using the Kaplan-Meier method. A multivariate analysis was performed for prognostic factors predictive of absolute survival. RESULTS: Multivariate analysis revealed tumor type (osseous vs. extramedullary) to be predictive of absolute survival (p = 0.12). Factors not predictive of survival were age, sex, use of chemotherapy, immunoglobulin level, and type of immunoglobulin elevated. Patients with osseous tumors had a lower survival rate than those with extramedullary tumors (55% vs. 80% at l0 years, p = 0.06). Multiple myeloma was more likely to develop in patients with osseous tumors (54% vs. 11% at l0 years, 100% vs. 33% at 15 years, p = 0.03). Of patients in whom multiple myeloma developed, those with osseous tumors had a poorer survival rate after development of myeloma (32% vs. 100% at 5 years, p = 0.11). Local relapse developed in 1 patient with an osseous tumor 10 months after treatment with 28.3 Gy in 14 fractions; this was controlled with an additional 28.3 Gy in 10 fractions. Local failure did not develop in any patient with an extramedullary tumor. CONCLUSIONS: Radiotherapy is an effective local treatment for solitary plasmacytoma. Osseous tumors were found to have a poor prognosis compared with extramedullary tumors. Editor's Comments: This succinct paper reviews all the essential things that radiation oncologists should know about solitary plasmacytomas. ****************** Lung/Mediastinum: Cox 12/96 No Reference Selected. ****************** GU: Roach 12/96 No Reference Selected. ****************** Radiobiology: Withers 12/96 AU: MacieJewski B, Skladowski K, Pilecki B, Taylor JM, Withers RH, Miszczyk L, Zajusz R, Suwinski R. TI: Randomized clinical trial on accelerated 7 days per week fractionation in radiotherapy for head and neck cancer. Preliminary report on acute toxicity. SO: Radiother Oncol 1996; 40:137-145. Abstract: PURPOSE: Toxicity of an accelerated 7 days per week fractionation schedule (arm A) was evaluated and compared with a conventional 5 days per week treatment (arm B) in a randomized trial. MATERIALS AND METHODS: Forty-four patients with squamous cell carcinoma of the head and neck in stage T2-4 N0-1 M0 were included in the study. Total dose and dose per fraction of 2.0 Gy given once-a-day at 24h intervals were the same in both arms of the trial. The only difference was the overall treatment time being 5 weeks in arm A and 7 weeks in arm B. RESULTS: Analysis of severe mucosal reactions shows significant difference between arm A and B, with regard to both maximum score and duration of severe mucositis. Confluent mucositis (score > 15 according to the Dische system) lasting longer than 3 weeks developed in 48% of patients in arm A and only in 5% in arm B. In group A seven (30%) late effects (osteo- and soft tissue necrosis) occurred during 7-12 month follow-up with two reactions (10%) in group B being suspected as late effects. There was significant association between acute reactions and late effects in arm A, suggesting that the late effects are consequential. CONCLUSION The high incidence of severe acute reactions and consequential late effects suggests that the accelerated treatment in arm A (using daily fractions of 2.0 Gy, 7 days per week) gives unacceptable toxicity. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC