From daemon Thu Jan 2 17:43:23 1997 Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id RAA14289 Message-Id: <199701030143.RAA14289@net.bio.net> To: radoncjc@net.bio.net Date: Thu, 2 Jan 97 15:40:03 HST Reply-To: radoncjc@net.bio.net From: bjg@mhpcc.edu (Brian Goldsmith) Subject: January 1997 Internet Radiation Oncology Journal Club (IROJC) January 1997 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 20th 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: Head and Neck 1/97. (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 January about a December 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 1/97 AU: Li FP; Breslow NE; Morgan JM; Ghahremani M; Miller GA; Grundy PE; Green DM; Diller LR; Pelletier J. TI: Germline WT1 mutations in Wilms' tumor patients: preliminary results. SO: Med Pediatr Oncol 1996 Nov;27(5):404-7. Abstract: We conducted a comparative study of the prevalence of germline WT1 mutations in patients with Wilms' tumor. Patients in Group 1 have familial Wilms' tumor, bilateral disease, associated urogenital anomalies, and/or second cancers. Those in Group 2 are unilateral, sporadic Wilms' patients without other associated conditions. Patients with aniridia or Denys-Drash syndrome are known to have WT1 alterations, and are excluded from this study. Preliminary results on 96 subjects show that the overall germline WT1 mutation frequency is low (< 5%). The work to date establishes the feasibility of identifying patients with germline WT1 mutations and, in the future, offering genetic predisposition testing to at-risk relatives. However, genetic predisposition testing of children for WT1 mutations raises many ethical, legal, and psychosocial issues; research is needed to evaluate risks and benefits. Editor's comments: The November 1996 issue of MPO, Volume 27, Number 5 is worthy of saving in your personal library. This issue displays the proceedings of the Second International Conference on Molecular and Clinical Genetics of Childhood Renal Tumors, which was held in Philadelphia, May, 1995. The article by Li et al is one of several excellent articles updating the reader on the explosion of new information regarding the molecular genetics of Wilms' Tumor. The introductory overview by Grundy and Coppes and the final paper by Knudson are also excellent reading. Today there is a better than 95% survival rate for Wilms' tumor patients. The molecular and clinical genetics of Wilms' Tumor are an important part of the understanding of this disease. This issue of MPO is important reading for all Oncologists. ****************** Head/Neck/Skin: Mendenhall 1/97 AU: Hayakawa K; Mitsuhashi N; Akimoto T; Maebayashi K; Ishikawa H; Hayakawa K; Sukurai H; Takahashi T; Kamei T; Niibe H. TI: The effect of overall treatment time of radiation therapy on local control of T1-stage squamous cell carcinoma of the glottis. SO: Laryngoscope 106:1545-7, 1996. Abstract: From 1975 to 1990, 72 patients with T1 glottic cancer, excluding a verrucous type of carcinoma, were treated with radiation therapy (RT). All treatments were given with a standard fractionation of 2 Gy per day. The total dose to the tumor ranged from 60 to 70 Gy. Six patients received a split-course RT. The overall local control rate was 87% at 5 years. Forty-one patients who completed RT in 45 days or less had a 5 year local control rate of 95%. Sixteen patients who completed a treatment course in 46 to 49 days had a local control rate of 81%. Fifteen patients with a treatment course of more than 50 days had a local control rate of 73%. There was a statistically significant difference in local control rates among the three groups (P<.05). The split course RT group had a 5-year local control rate of 50%; that rate was statistically significantly inferior to that of the continuous course group (P<.001). Multivariate analysis also showed that an interruption of the treatment course was an important parameter in relation to the local control. The prolongation of standard RT schedules adversely affected local control of T1 glottic carcinoma and, therefore, should be avoided whenever possible. ****************** GYN: Grigsby 1/97 AU: Yeoh E; Sun WM; Russo A; Ibanez L; Horowitz M. TI: A retrospective study of the effects of pelvic irradiation for gynecological cancer on anorectal function. SO: Int J Radiat Oncol Biol Phys 1996 Jul 15;35(5):1003-10. Abstract: PURPOSE: To evaluate the prevalence of anorectal dysfunction following therapeutic pelvic irradiation. METHODS AND MATERIALS: Anorectal function was evaluated in 15 randomly selected patients (aged 47-84 years) who had received pelvic irradiation for treatment of carcinoma of the uterine body and cervix 5 and 10 years earlier. The following parameters were assessed in each patient: (a) anorectal symptoms (questionnaire), (b) anorectal pressures at rest and in response to rectal distension, voluntary squeeze, and increases in intraabdominal pressure (multiport anorectal manometry with concurrent electromyography of the anal sphincters), (c) rectal sensation (rectal balloon distension) and, (d) anal sphincteric morphology (ultrasound). Results were compared with those obtained in nine female control subjects. RESULTS: Ten of the 15 patients had urgency of defecation and 4 also suffered fecal incontinence. Basal anorectal pressures measured just proximal to the anal canal (p = 0.05) and anorectal pressures generated in response to voluntary squeeze measured at the anal canal were less (p < 0.01) in the patients. The fall in anal pressures in response to rectal distension was greater in the patients (p < 0.05) and the desire to defecate occurred at lower rectal volumes (p < 0.05). The slope of the pressure/volume relationship in response to rectal distension was greater (p < 0.05) in the patients, suggestive of a reduction in rectal compliance. In 14 of the 15 patients at least one parameter of anorectal motor function was outside the control range. There was no difference in the thickness of the anal sphincters between the two groups. CONCLUSION: Abnormal anorectal function occurs frequently following pelvic irradiation for gynecological malignant diseases and is characterized by multiple dysfunctions including weakness of the external anal sphincter, stiffness of the rectal wall, and a consequent increase in rectal sensitivity. ****************** GI: Tepper 1/97 AU: Shibata D; Reale MA; Lavin P; Silverman M; Fearon ER; Steele G Jr; Jessup JM; Loda M; Summerhayes IC. TI: The DCC protein and prognosis in colorectal cancer. SO: N Engl J Med 1996 Dec 5;335(23):1727-32. Abstract: BACKGROUND: Allelic loss of chromosome 18q predicts a poor outcome in patients with stage II colorectal cancer. Although the specific gene inactivated by this allelic loss has not been elucidated, the DCC (deleted in colorectal cancer) gene is a candidate. We investigated whether the expression of the DCC protein in tumor cells is a prognostic marker in colorectal carcinoma. METHODS: The expression of DCC was evaluated immunohistochemically in 132 paraffin-embedded samples from patients with curatively resected stage II and III colorectal carcinomas. The Cox proportional-hazards model was used to adjust for covariates including age, sex, tumor site, degree of tumor differentiation, and use of adjuvant therapy. RESULTS: The expression of DCC was a strong positive predictive factor for survival in both stage II and stage III colorectal carcinomas. In patients with stage II disease whose tumors expressed DCC, the five-year survival rate was 94.3 percent, whereas in patients with DCC-negative tumors, the survival rate was 61.6 percent (P<0.001). In patients with stage III disease, the respective survival rates were 59.3 percent and 33.2 percent (P=0.03). CONCLUSIONS: DCC is a prognostic marker in patients with stage II or stage III colorectal cancer. In stage II colorectal carcinomas, the absence of DCC identifies a subgroup of patients with lesions that behave like stage III cancers. These findings may thus have therapeutic implications in this group of patients. Editor's comments: There have been a huge number of articles over the past few years on prognostic factors in colon and rectal cancer. Consistently stage has been shown to be an important factor, but now there are multiple studies of molecular markers as well as clinical and pathological factors that may be of importance. It is important that these issues get sorted out. At the present time the clinician cannot possibly make sense of all the markers that are predictive in one study or another. It will clearly be the case that many of these factors will be dependent on one another, and some will reflect a basic biological difference while others will simply express a secondary effect which is associated with a basic factor. The article discussed here is of greater interest than many, because there is a connection of DCC with carcinogenesis. However, the true function of the DCC protein is unclear although the evidence does suggest that it acts as a tumor suppressor. The effect on prognosis seen in this article is substantial. Patients with DCC positive Stage III tumors did as well as DCC negative Stage II tumors. To make my point about too much information is the fact that in December there were (at least) two other articles of a similar nature (I had to pick only one for this journal club). One was from Memorial Sloan-Kettering (JCO 14: 3133-3140, 1996) looking at matrix metalloproteinase (MMP)-9 RNA expression and prognosis in colorectal cancer. The MMP's are extracellular matrix degrading proteases which is an essential event for tumor invasion and metastasis. Overexpression was correlated with an enormous effect on outcome, even when stage corrected. A second article was in the Annals of Surg Onc (3:(6): 574-579, 1996 from Australia. This demonstrated a higher expression of c-myc, c-ergB-2/neu, PCNA, and p53 in tumors that had metastasized than in non-metastatic tumor. I am not sure what to do with all of this, but it is likely to get more confusing before it gets resolved. For the time being, we are stuck with having a huge amount of information and not knowing what to do with it. For adjuvant therapy, I would certainly not advise anyone to make clinical decisions based on any of these preliminary reports. In the future we will hopefully be able to integrate this information into our decision making process to decide on adjuvant therapy and other management issues, and hopefully will find crtical parts of the malignant pathway that can be biologically modified to reverse the malignant process or to target specifically malignant cells. ****************** CNS: Larson 1/97 No Reference Selected. ****************** Physics/Dosimetry: Purdy 1/97 AU: Goitein M; Niemierko A. TI: Intensity modulated therapy and inhomogeneous dose to the tumor: a note of caution [editorial]. SO: Int J Radiat Oncol Biol Phys 1996 Sep 1;36(2):519-22. ****************** Breast: Recht 1/97 AU: Karasek K; Deutsch M. TI: Lumpectomy and breast irradiation for breast cancer after radiotherapy for lymphoma. SO: Am J Clin Oncol 1996 Oct;19(5):451-4. Abstract: Six women received irradiation for lymphoma (Hodgkin's disease, n = 5; non-Hodgkin's disease, n = 1) to at least a mediastinal field (n = 2) or to a mantle field (n = 4), and subsequently developed breast cancer 10-27 years later. Three patients also received chemotherapy as a component of therapy for lymphoma. For breast cancer, all were treated with lumpectomy and breast irradiation to 5,000 cGy in 25 fractions plus a 1,000 cGy/5 fraction boost to the operative area using electrons. Two patients received adjuvant chemotherapy and three others tamoxifen for breast cancer. All women are alive and free of disease 15-118 months (median, 60 months) following breast irradiation. There have been no cases of significant acute reactions and no late sequelae such as skin pigmentation changes subcutaneous fibrosis, rib fractures, cardiac disease, or pulmonary fibrosis. The cosmetic result is considered good or excellent in all. Lumpectomy and breast irradiation is not contraindicated in the woman who develops breast cancer many years after irradiation of lymph node regions above the diaphragm for lymphoma. Editor's Comments: Prior therapeutic irradiation to the ipsilateral breast has been considered a strong or absolute contraindication to breast-conserving surgery and radiotherapy by nearly all writers and consensus panels. Although the conventional wisdom on this subject seems logical enough, this important article suggest it is not correct, at least for patients treated with relatively moderate doses (30-44 Gy) 10-27 years before developing a breast cancer. (The senior author has previously challenged this notion with regards to reirradiation of patients treated for a cancer of the breast previously also, but the results in that situation - so far described only in abstract form - are much less compelling. See Proc Am Soc Clin Oncol 1992;11:60.) The authors are therefore to be applauded for having taken the substantial risks, had they been wrong, associated with their decision to treat these patients. This article also raises a difficult issue: namely, how much evidence is needed to warrant a change in selection or treatment policies? It does not seem likely many other patients have been so treated, giving the prevailing dogmas (which I have shared). Therefore, we are unlikely to see more such series published soon. What should be done? (I will be happy to reply individually or collectively on this matter.) ****************** RES: Hoppe 1/97 No Reference Selected. ****************** Lung/Mediastinum: Cox 1/97 No Reference Selected. ****************** GU: Roach 1/97 No Reference Selected. ****************** Radiobiology: Withers 1/97 AU: Saunders MI; Dische S; Barrett A; Parmar MK; Harvey A; Gibson D. TI: Randomised multicentre trials of CHART vs conventional radiotherapy in head and neck and non-small-cell lung cancer: an interim report. CHART Steering Committee. SO: Br J Cancer, 1996 Jun, 73:12, 1455-62. Abstract: While radiotherapy is proceeding, tumour cells may proliferate. The use of small individual doses reduces late morbidity. Continuous hyperfractionated accelerated radiation therapy (CHART), which reduces overall treatment from 6-7 weeks to 12 days and gives 36 small fractions, has now been tested in multicentre randomised controlled clinical trials. The trial in non-small-cell lung cancer included 563 patients and showed improvement in survival; 30% of the CHART patients were alive at 2 years compared with 20% in the control group (P = 0.006). In the 918 head and neck cases, there was only a small, non-significant improvement in the disease-free interval. In this interim analysis there was a trend for those with more advanced disease (T3 and T4) to show advantage; this will be subject to further analysis when the data are more mature. The early mucosal reactions appeared sooner and were more troublesome with CHART, however they quickly settled; so far no difference in long-term morbidity has emerged. These results support the hypothesis that tumour cell repopulation can occur during a conventional course of radiotherapy and be a cause of treatment failure. Editor's Comments: This paper presents the overall result of the CHART trial for cancers of the head & neck and lung. This is an initial report and will be followed by others. It shows: 1) it is logistically possible, at least in Europe, to give an intensive 12-day continuous treatment. 2) the results are slightly better that in their controls, the local control rates were slightly better and the side effects (from previous reports on salivary function) were less. The major exception is the spinal cord which should never get 3 fractions/day, even if each fraction is 1.5Gy (because it appears the cord is slow at repairing sublethal injury). At ASTRO, Dr. Dische updated these results and there will be papers following which show that the improvement in local control in larynx is significantly better than in the total group. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC From daemon Thu Jan 2 19:18:30 1997 Received: (from daemon@localhost) by net.bio.net (8.6.12/8.6.6) id TAA22064 Message-Id: <199701030318.TAA22064@net.bio.net> To: radoncjc@net.bio.net Date: Thu, 2 Jan 97 17:17:11 HST Reply-To: radoncjc@net.bio.net From: bjg@mhpcc.edu (Brian Goldsmith) Subject: Jan97 IROJC Erratum -- Head/Neck/Skin The January 1997 IROJC Initial Posting erroneously deleted the first line of the Hayakawa abstract (Head/Neck/Skin: Mendenhall 1/97). The reference and complete abstract are reprinted below. Please note the error, and correct your copy. Thank you for your patience. Brian Goldsmith, M.D. Moderator, IROJC --------------------- Head/Neck/Skin: Mendenhall 1/97 AU: Hayakawa K; Mitsuhashi N; Akimoto T; Maebayashi K; Ishikawa H; Hayakawa K; Sukurai H; Takahashi T; Kamei T; Niibe H. TI: The effect of overall treatment time of radiation therapy on local control of T1-stage squamous cell carcinoma of the glottis. SO: Laryngoscope 106:1545-7, 1996. Abstract: >From 1975 to 1990, 72 patients with T1 glottic cancer, excluding a verrucous type of carcinoma, were treated with radiation therapy (RT). All treatments were given with a standard fractionation of 2 Gy per day. The total dose to the tumor ranged from 60 to 70 Gy. Six patients received a split-course RT. The overall local control rate was 87% at 5 years. Forty-one patients who completed RT in 45 days or less had a 5 year local control rate of 95%. Sixteen patients who completed a treatment course in 46 to 49 days had a local control rate of 81%. Fifteen patients with a treatment course of more than 50 days had a local control rate of 73%. There was a statistically significant difference in local control rates among the three groups (P<.05). The split course RT group had a 5-year local control rate of 50%; that rate was statistically significantly inferior to that of the continuous course group (P<.001). Multivariate analysis also showed that an interruption of the treatment course was an important parameter in relation to the local control. The prolongation of standard RT schedules adversely affected local control of T1 glottic carcinoma and, therefore, should be avoided whenever possible.