From daemon Mon Aug 23 13:41:58 1999 Received: (from daemon@localhost) by net.bio.net (8.9.1a/8.9.1) id NAA27397; Mon, 23 Aug 1999 13:41:58 -0700 (PDT) Message-Id: <199908232041.NAA27397@net.bio.net> To: radoncjc@net.bio.net Date: Thu, 05 Aug 1999 10:36:03 -0400 Reply-To: radoncjc@net.bio.net From: Brian Goldsmith Subject: August 1999 Internet Radiation Oncology Journal Club (IROJC) August 1999 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 51st collection of references suggested for attention and discussion by the IROJC's Board of Editors: Sarah Donaldson, M.D. Editor, Pediatric Radiation Oncology Robert Foote, M.D. Editor, Head and Neck / Skin Radiation Oncology Abram Recht, M.D. Editor, Breast Radiation Oncology Rich Hoppe, M.D. Editor, Reticuloendothelial System Radiation Oncology Dan Petereit, M.D. Editor, Gynecological Radiation Oncology Andrew Turrisi, M.D. Editor, Lung and Mediastinum Radiation Oncology Joel Tepper, M.D. Editor, Gastrointestinal and Soft Tissue Sarcoma Radiation Oncology Mack Roach, M.D. Editor, Genitourinary Radiation Oncology Glenn Bauman, M.D. Ph.D. Editor, Central Nervous System Radiation Oncology Rod Withers, M.D., D.Sc. Editor, Radiobiology Jim Purdy, Ph.D. Editor, Radiation Oncology Physics and Dosimetry ----------------------------------------------------- You're encouraged to critically review this set of references and respond by posting your comments to the IROJC readership at radoncjc@net.bio.net. Comments should be in compliance with IROJC commentary rules (see below). In the month that follows this posting of references, submitted comments will be delivered to the e-mail boxes of the IROJC readership, with the goal of stimulating a professional discussion of these references and their subjects. ------------------------------------------------------------ ARCHIVED IROJC POSTINGS and commentary are available on the World Wide Web! Look for them on http://www.bio.net/ Click on the "Access the BIOSCI/bionet Newsgroups" hyperlink, and then go to "RADIATION-ONCOLOGY/Prototype". Or directly access the RADIATION-ONCOLOGY folder at http://www.bio.net/hypermail/RADIATION-ONCOLOGY/ There's also a freeWAIS search tool at the website, for searching archived postings for keywords or phrases! ------------------------------------------------------------ Commentary Rules: (1) Please cite the subject category in the header of your e-mail message, e.g., Subject: CNS 8/99. (2) Address the readership at large - not the Editor who suggested the reference. The Editor is under no obligation to respond to questions posed by the IROJC readership. (3) The Editor's selection is not necessarily an endorsement of the authors' conclusions. In fact, articles may be selected for criticism. (4) Comments posted to the Internet are public. Professional wording is prudent. (5) Comment only on journal articles that you have read recently, and please keep comments specific. (6) In order to minimize confusion, limit comments to the current month's list of references. (7) Please sign all comments and questions to the IROJC. By identifying yourself, you promote a more collegial and friendly environment! (8) Address to the Moderator (briandeb@bellatlantic.net) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 8/99 AU: Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA, Kun LE, Walter AW, Evans WE, Pui CH. TI: High incidence of secondary brain tumours after radiotherapy and antimetabolites. SO: Lancet 1999 Jul 3;354(9172):34-9 URL: http://www.thelancet.com/newlancet/sub/issues/vol354no9172/early34.html Abstract: BACKGROUND: Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. METHODS: We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. FINDINGS: The incidence of brain tumours among irradiated children (six of 52, 12.8% [SE 5.0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p equals 0.0008) and with other protocols that included cranial radiotherapy (p<0.0001). Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism. The 8-year cumulative incidence of brain tumour among children with defective versus wild-type thiopurine methyltransferase phenotype was 42.9% (SE 20.6) versus 8.3% (4.7; p equals 0.0077). This protocol differed from previous protocols, in that more intensive systemic antimetabolite therapy was given before and during radiotherapy. INTERPRETATION: These data support the elimination of prophylactic radiotherapy for acute lymphoblastic leukaemia except in patients at high risk of central-nervous-system relapse. Underlying genetic characteristics and treatment variables may be associated with an increased risk of radiation-associated brain tumours. Editor's comments: In forming my comments, I consulted with Dr. Larry Kun, who is a co-author on this paper and senior author on a prior paper from the same investigators which I recommend you also read as a companion to the Lancet paper. It is: AU: Walter AW, Hancock ML, Pui C-H, Hudson MM. Ochs JS, Rivera GK, Pratt CB, Boyett JM, and Kun LE. TI: Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital. SO: J Clin Oncol 16: 3761-3767, 1998 URL: http://www.jco.org/cgi/content/abstract/16/12/3761 It is important to keep in perspective that the overall incidence of post-therapy malignant gliomas in children treated for ALL is 0.5-2% with follow up durations of 10-20 years. When managing children with ALL one must find balance between the efficacy of our treatments and their toxicities - those from irradiation, and those from systemic and intrathecal chemotherapy. When one limits exposure to radiation, then higher doses, and longer durations of chemotherapy are required to treat and/or prevent CNS leukemia. Investigators at St Jude Children's Research Hospital have pioneered a series of carefully planned and conducted clinical trials with aim to decreasing and eliminating CNS leukemia. The Lancet article points to an interesting interaction of antimetabolite exposure with irradiation as co-carcinogens observed in their Total Therapy Study XII. While we usually think of alkylating agents as culprits to secondary malignancies, it is possible that the anti-metabolites also play a broader role than previously recognized. While we all search for the least toxic therapy and respect the clear indications for use of radiotherapy when treating the brain, it is important to note that a recent POG frontline ALL study required closure due to Methotrexate related neurotoxicity. Thus, "More is not necessarily better" with respect to all therapy directed to the central nervous system. ****************** Head/Neck/Skin: Foote 8/99 AU: van Dam FS, Hilgers FJ, Emsbroek G, Touw FI, van As CJ, de Jong N TI: Deterioration of olfaction and gustation as a consequence of total laryngectomy. SO: Laryngoscope 1999 Jul;109(7 Pt 1):1150-5. Abstract: INTRODUCTION: After total laryngectomy the absence of a nasal airflow results in a decrease in olfaction and perception of flavors. MATERIALS AND METHODS: Odor perception was assessed in 63 laryngectomized patients with two different olfactory tests. The methods used by patients to smell were observed during olfactory testing. Patients' judgment about their olfaction and gustation was assessed by means of a structured questionnaire, semistructured interview, and self-rating. RESULTS: Based on the results of the olfactory tests, patients were categorized as "smellers" and "nonsmellers." Approximately one third of the patients were able to smell the odorous substances used in the olfactory tests. The smellers more often used a variety of methods to smell than the nonsmellers (P < .002); in most patients the method consisted of active use of facial muscles. Patients appeared well able to judge their own odor perception. Compared with the smellers, the nonsmellers judged their odor perception as worse (P < .003) and reported a more severe decrease in gustation after the operation (P < .033). The results of this study in laryngectomized patients confirm the interrelation between olfaction and gustation: the nonsmellers reported a poorer gustation and a more severe decrease in gustation and appetite than both the smellers and a reference group of elderly persons (P < .05). Patients who reported a deterioration of olfaction and gustation tended to experience negative consequences such as the inability to smell smoke, leaking gas, or agreeable odors. CONCLUSION: Olfaction and odor-related flavor sensation are seriously deteriorated after total laryngectomy. Editor's comments: Quality of life issues related to total laryngectomy have focused mainly on the loss of a lung powered voice. When physicians were surveyed regarding the major quality of life issues in patients undergoing total laryngectomy, the majority thought it was the loss of laryngeal speech. However, when patients who had undergone a total laryngectomy were surveyed, the most important detriment to their quality of life according to them was the problems associated with having a stoma--inability to blow their nose when they had a cold, severe limitations in showering or swimming, constant mucous production and cough, people staring in public, sexual dysfunction, pulmonary problems, etc. Additional difficulties associated with a stoma are the effects it has on the sense of smell and taste. In this study, olfaction was assessed in patients who had undergone a laryngectomy by means of olfactory tests. Taste and olfaction was assessed by means of a structured questionnaire, semi-structured interview, and self-rating. The influence olfactory and taste problems had on daily life was also assessed. Significant findings included: 68% of the patients were unable to smell. Both those who could still smell and those who could not experienced significant decreases in odor perception, taste and appetite. Additional negative consequences reported by patients included an unsafe feeling in the inability to smell smoke, leaking gas or the burning of food; the absence of pleasant odors; and the impact on hygiene--such as the inability to smell bodily odors. 62% reported significant changes in taste. Negative consequences included changes in dietary habits and the inability to enjoy food (reported by 33%). 57% were not informed preoperatively about the potential for the loss of smell and/or taste. Only 8% received instructions about techniques to improve odor perception during rehabilitation. Some patients had discovered on their own techniques to improve airflow through the nasal cavity in order to improve the sense of smell. Some used facial muscles, neck muscles or jaw movements to induce or create an air stream in the nose through which odorous substances were able to reach the olfactory organ. Pushing and releasing the soft palate from the posterior pharyngeal wall seemed to be effective too. Moving the object to be smelled around the nose was frequently performed to improve smell. Intensive chewing, especially with the mouth closed, and back-and-forth movements of food in the mouth seemed to improve taste. This type of chewing induces an air stream into the oral cavity that can extend backwards into the nasal cavity to stimulate the olfactory organ. These techniques should be formally studied to determine their efficacy. In the interim they can be suggested to patients as ways to improve smell and taste after total laryngectomy. Taste and smell should be included in quality of life assessments in patients with head and neck cancer. ****************** GYN: Petereit 8/99 No Reference Selected ****************** GI / Soft Tissue Sarcoma: Tepper 8/99 No Reference Selected ****************** CNS: Bauman 8/99 AU: Merchant TE, Happersett L, Finlay JL, Leibel SA. TI: Preliminary results of conformal radiation therapy for medulloblastoma. SO: Neuro-Oncology [serial online], Doc. 98-01, June 15, 1999 URL: http://neuro-oncology.mc.duke.edu/neuro-onc/files/issues/present/merchant/index.html Abstract: Radiation therapy for medulloblastoma consists of postoperative irradiation of the intracranial and spinal subarachnoid volume with an additional boost to the primary site of disease in the posterior fossa. The entire posterior fossa is usually included in the boost volume. Conformal radiation therapy techniques may be used to boost the primary site alone and substantially reduce the dose received by normal tissues, including the supratentorial brain, the middle and inner ear, and the hypothalamus. Using these techniques to irradiate only the tumor bed or residual tumor and not the entire posterior fossa represents a new paradigm in the treatment of medulloblastoma. In this study, we examine the use of conformal radiation therapy in the treatment of 14 patients with medulloblastoma. These patients were treated with multiple static, individually shaped, noncoplanar beams directed at the primary site after craniospinal irradiation. Excluding two patients who had previously received irradiation to the posterior fossa, the mean dose delivered to the primary site was 5715 cGy. Among the medulloblastoma patients (n equals 10) who received immediate postoperative radiation therapy, no failures have occurred with a median follow-up of 42 months (range from 30 to 54 months). To demonstrate the differences in the distribution of dose to normal tissues when comparing conventional and conformal techniques, dose-volume histograms of the total brain, middle and inner ear, hypothalamus, and temporal lobe were created and presented for an example case. The neurologic, neuroendocrine, and neurocognitive outcome for patients with medulloblastoma may be influenced with the use of conformal radiation therapy. The use of these techniques should be formally tested in prospective studies of rigorously staged patients with failure rate monitoring. Editor's comments: In this series a small number of patients were treated with conformal radiotherapy to the postoperative tumor bed and imageable residual disease for favourable risk medulloblastoma. Modest dose escalation to a median dose of 57Gy was possible and no failures have been observed after a median followup of 42 months. Potential pitfalls in the treatment of medulloblastoma with radiation have been summarized recently by Halperin (Halperin EC. Impact of radiation technique upon the outcome of treatment for medulloblastoma. Int J Radiat Oncol Biol Phys. 1996 Aug 1;36(1):233-9) and cautions against an abrupt shift away from the posterior fossa boost. Certainly the technique described by Merchant et al is technically demanding. Accurate delineation of the tumor bed and residual disease for the 3D treatment plan and the treatment of multiple unconventional beam angles in a pediatric (read: fidgety) population is not to be undertaken lightly. Nevertheless, the potential lower toxicity of such highly conformal treatments is attractive. The authors call for the prospective evaluation of conformal boosts in clinical trials...the QA of such a trial (especially a multi-institutional trial) will be formidible and will probably require the resources of a 3D ready group like the RTOG. Like the institutions that pioneered the use of lower doses of radiation with chemotherapy for favourable risk medulloblastomas; Merchant et al point the way towards yet another potential method of lowering the late toxicity in a curable malignancy. The cautious introduction (and prospective evaluation) of such smaller volume, conformal or IMRT boosts in medulloblastomas in institutions with expertise in these technically demanding setups should be followed with interest. In the interim, there are some modest gains to be made in lowering toxicity through the use of conformal posterior fossa boosts using posterior wedged pairs. Such boosts are easier to plan, deliver and verify and do spare the auditory apparatus and temporal lobes to a greater extent than the typical lateral opposed pair. Whether one could safely dose escalate to the gross residual disease on top of a conformal posterior fossa boost also remains to be demonstrated. As an aside, this article appears in a new journal "Neuro-Oncology". The inaugural issue of this journal appeared in January 1999 and serves as the journal for the Society for Neuro-Oncology (SNO). The journal is also available online (http://neuro-oncology.mc.duke.edu) and can be accessed without a subscription until at least October 1999 if you would like a preview. Subscriptions for the journal and membership in SNO is also available through this website. The journal seems strong on good review articles, particularly on the molecular genetics of brain tumors, with a growing number of original research articles appearing. The journal would benefit greatly from the support of the radiation oncology community, particularly original article submissions. While I do belong to SNO, I am not on the editorial board for the journal, nor do I get a commission for subscriptions...I just would like to see the journal flourish as the early issues seem very well produced. ****************** Physics/Dosimetry: Purdy 8/99 No Reference Selected ****************** Breast: Recht 8/99 AU: Yamada Y, Ackerman I, Franssen E, MacKenzie RG, Thomas G. TI: Does the dose fractionation schedule influence local control of adjuvant radiotherapy for early stage breast cancer? SO: Int J Radiat Oncol Biol Phys 1999 Apr 1;44(1):99-104. Abstract: PURPOSE: To explore the correlation between dose fractionation and local control for the adjuvant radiotherapy of early stage breast cancer. METHODS AND MATERIALS: A matched-pair analysis of early stage invasive breast cancer treated adjuvantly with two different dose fractionation schedules, 4000 cGy in 16 fractions (Cohort A) vs. 5000 cGy in 25 fractions (Cohort B) was undertaken to compare local control rates. A systematic review of the published experience in similar patient populations was conducted and the reported dose fractionation schedule was converted to a biologic effect dose (BED) based upon the linear quadratic equation. The BED was then used as a basis for comparing reported local control rates with different dose fractionation schemes. RESULTS: The 118 patient pairs were matched from Cohort A and Cohort B using known significant prognostic factors including age, histology, surgical margins, receptor status, lymphvascular space invasion, extensive intraductal disease, lymph node status, and systemic therapy. The local recurrence rate at 5 years for those treated with 4000 cGy (BED equals 65 cGy4) and 5000 cGy (BED equals 75 cGy4) was 12.7% and 6.8%, respectively, and this difference was not statistically significant (p equals 0.09). Overall survival was 84% at 5 years for both groups. Comparison of the different dose fractionation schemes reported in the literature revealed a highly statistically significant difference between those treated with less than a BED of 75 Gy4 and those treated with a BED of 75 Gy4 or greater. CONCLUSION: Although not statistically significant, there was a trend in the matched pair analysis which suggests that 4000 cGy in 16 fractions (BED equals 65 cGy4) provides inferior local control compared to 5000 cGy in 25 fractions (BED equals 75 cGy4). Moreover, the literature review demonstrates that a dose control relationship may exist for local control in the adjuvant setting. A dose fractionation schedule equivalent to 5000 cGy in 25 fractions to the whole breast may represent the optimal dose fractionation schedule for local control. Editor's comments: An important practical question in these days of increasing budgetary stringency in health care is the optimal fractionation and total dose needed to perform a particular job well withan acceptable risk of complications. Those of us who practice in the United States remain somewhat sheltered from this still, but this problem has been a long- standing one for colleagues in Canada and Europe (particularly in the United Kingdom). The current article deals with this problem as it applies to the whole-breast phase of breast-conserving therapy. (The issue of giving a boost or not is another related issue; see my discussion of this in this Journal Club's archives of 5/97, with regards to a randomized trial conducted in Lyon, France; J Clin Oncol 1997;15:963-968; URL: http://www.bio.net/hypermail/RADIATION-ONCOLOGY/9705/0001.html) This important study from the Toronto-Sunnybrook Regional Cancer Centre in Toronto suggests that, in patients treated without a boost, a dose of 50 Gy in 25 fractions results in a substantially lower recurrence rate than 40 Gy in 16 fractions. However, the analysis does not separate results according to margin status or other prognostic factors. Other studies show that patients with negative margins have lower failure rates with similar short-course schemes than were seen here (for example, 5-year failure rate of 6% in a study from British Columbia, Olivotto et al, Radiother Oncol 1996;7-13; and a crude rate of 3.5% (19/541) in a series from the Christie Hospital in Manchester, England, at a median FU of 4.7 years, Magee et al, Clin Oncol 1999;11:40-45; neither group gave a boost). Cosmetic results and complication rates were not reported in the Toronto study, but in the British columbia study these were quite comparable to series using daily doses of 1.8-2 Gy. A cautionary note has been raised by a review of the Ontario Cancer Registry, in which patients with left-sided cancers had a higher cardiac mortality rate (2%) than patients with right-sided cancers (1%); the great majority of patients received 40 Gy in 16 fractions to breast tangents (without an attempt to include the IMNs); Paszat et al, Int J Radiat Oncol Biol Phys 1999;755-761. Randomized trials comparing different fractionation schemes are ongoing in the United Kingdom (the START trial) and Ontario. These will hopefully help settle some of these questions. ****************** RES: Hoppe 8/99 AU: Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, Montserrat E, Radford JA, Salles G, Schmitz N, Symann M, Armitage JO, Coiffier B, Philip T. TI: International Consensus Conference on high-dose therapy with hematopoietic stem-cell transplantation in aggressive non-Hodgkin's lymphomas: report of the jury. SO: Ann Oncol 1999 Jan;10(1):13-9. Editor's comments: The "Jury" recommended high dose therapy (HDT) for patients with chemosensitive first or subsequent relapse, based upon the PARMA study (see the January 1996 IJROC RES selection: http://www.bio.net/hypermail/RADIATION-ONCOLOGY/9601/0000.html). However, HDT was not recommended for patients in chemorefractory first or subsequent relapse. The data for HDT as a component of initial induction therapy for high risk patients (variably defined) were judged to be inconclusive at this point, and additional studies were recommended. They specifically urged these studies be done for patients in the "high-intermediate" or "high-risk" categories according to the International Prognostic Index (3 or more unfavorable factors). The role of radiation therapy was not addressed in any depth. The absence of randomized studies made it impossible to determine whether TBI-containing regimens were superior to non-TBI regimens. The role of local RT was not discussed, although a significant proportion of patients often have some RT as a component of their high dose therapy (40% in the PARMA study). ****************** Lung/Mediastinum: Turrisi 8/99 AU: Nestle U, Walter K, Schmidt S, Licht N, Nieder C, Motaref B, Hellwig D, Niewald M, Ukena D, Kirsch CM, Sybrecht GW, Schnabel K. TI: 18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis. SO: Int J Radiat Oncol Biol Phys 1999 Jun 1;44(3):593-7. Abstract: PURPOSE: 18F-deoxyglucose positron emission tomography (FDG-PET) is increasingly applied in the staging of lung cancer (LC). This study analyzes the potential contribution of PET in radiotherapy planning for LC with special respect to tumor-associated atelectasis. METHODS AND MATERIALS: Thirty-four patients with histologically confirmed LC, who had been examined by PET during pretreatment staging, were included. All were irradiated after CT-based therapy planning with anterior/posterior (AP) portals encompassing the primary tumor and the mediastinum (CT portals, CP). The result of the PET examination was unknown in treatment planning. In retrospect, a PET portal (PP) was delineated and compared with the CP. RESULTS: In 12/34 cases, the shape and/or size of the portals were changed, primarily (n equals 10) the size of the fields was reduced. The median area of CP was 182 cm2 versus 167 cm2 of PP. Seventeen of 34 patients had dys- or atelectasis caused by a central primary tumor. In these cases, differences between CP and PP were significantly more frequent than in the other patients (8/17 vs. 3/17, p equals 0.03). CONCLUSION: In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals. This applies particularly for patients with tumor-associated dys- or atelectasis. Editor's comments: PET's are the new high technology on the block. Many centers, including my own, have access only at a distance. There are increasing reports of use and Medicare now pays for diagnostic evaluation in lung cancer. However, we send our patients 3 - 5 hours away (Charlotte or Durham) in order to get diagnostic information. Recent information says these studies help in diagnosing nodules, lymph nodes and that intensity of uptake may correlate with response and survival. The captioned paper looks at another issue: Can PET help define target volumes. This study emphasizes a role in distinguishing atelectasis from tumor. We also want to use it to define who has high risk of "size-occult" nodes. For particularly the medically inoperable patient, but also perhaps others, routine treatment of mediastinal and certainly supraclavicular nodes may not be mandatory any longer. Targeting tissues that "glow" in PET Scanners may reduce the target and ensuing toxicity. However, trials are needed to prove that there is not a substantial downside (compromise in survival or local control)if different, smaller, lesser normal tissue inclusive volume targets are selected for treatment. The PET may be a useful tool. As in all technologies, there may be a wave of rabid enthusiasm, followed by a valley of disappointment when false positives and negatives are discovered. This paper describes a wise use of this technology -- good luck to those of you that have it, and good wishes for those of us that don't. ****************** GU: Roach 8/99 No Reference Selected ****************** Radiobiology: Withers 8/99 TI: Radiation-induced emesis: a prospective observational multicenter Italian trial. The Italian Group for Antiemetic Research in Radiotherapy. SO: Int J Radiat Oncol Biol Phys 1999 Jun 1;44(3):619-25. Abstract: PURPOSE: A prospective observational multicenter trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and evaluate the use of antiemetic drugs in radiation oncology clinical practice. METHODS AND MATERIALS: Fifty-one Italian radiation oncology centers took part in this trial. The accrual lasted 2 consecutive weeks, only patients starting radiotherapy in this period were enrolled. Exclusion criteria were age under 18 years, and concomitant chemotherapy. Evaluation was based on diary cards filled in daily by patients during radiotherapy and 1 week after stopping it. Diary cards recorded the intensity of nausea and any episode of vomiting and retching. Prophylactic and symptomatic antiemetic drug prescriptions were also registered. RESULTS: Nine hundred thirty-four patients entered the trial, and 914 were evaluable. Irradiated sites were: breast in 211 patients, pelvis in 210 patients, head and neck in 136 patients, thorax in 129 patients, brain in 52 patients, upper abdomen in 42 patients, skin and/or extremities in 37 patients, and other sites in 97 patients. Vomiting and nausea occurred in 17.1% and 37.3% of patients, respectively, and 38.7 % patients had both vomiting and nausea. At multifactorial analysis, the only patient-related risk factor that was statistically significant was represented by previous experience with cancer chemotherapy. Moreover, two radiotherapy (RT)-related factors were significant risk factors for RIE, the irradiated site and field size. In fact, a statistically significant higher percentage of RIE was registered in upper abdomen RT and RT fields > 400 cm2. Although nonstatistically significant, patients receiving RT to the thorax and head and neck presented a higher incidence of RIE. Only a minority (14%) of patients receiving RT were given an antiemetic drug, and the prescriptions were more often symptomatic than prophylactic (9% vs. 5%, respectively). Different compounds and a wide range of doses and schedules were used; however, there is some evidence from our data that in spite of antiemetic prophylaxis, 46% of patients had vomiting, and 58% had nausea. The majority (93%) of the prophylactic group received oral 5-hydroxytriptamine receptor (5-HT3) antagonist (8 mg/day, 7 days/week). In the symptomatic group, 54% and 41% patients received 5-HT3 antagonists and metoclopramide, respectively. At multivariate analysis, no patient- or RT-related risk factor for RIE was found to influence significantly the prophylactic or symptomatic use of antiemetics. CONCLUSION: Our study provided useful data on epidemiology and characteristics of RIE. Previous chemotherapy, field size, and irradiated site (upper abdomen) were the only significant prognostic factors of RIE. A remarkable incidence of RIE was found in patients submitted to thoracic and head and neck RT. With this background of knowledge, it will be possible to better plan further studies on this important problem. Moreover, the low rate of antiemetics use and the wide variety of doses and schedules employed suggest the need to reinforce the "evidence based" approach to identify the best antiemetic approach to RIE. Editor's comments: This study reports on nausea and vomiting among more than 900 patients beginning radiation therapy in 51 centers in Italy over a 2-week period in 1996. Each patient kept a diary of their nausea and vomiting (including retching). Not surprising is the result of a multifactorial analysis which shows upper abdominal and large field irradiation to be risk factors. What is surprising is the high incidence recorded in patients being treated to other areas than upper abdomen. This was particularly so for thorax and head and neck (with incidences of 26% and 18%, respectively, but was also reported by, for example, 10% of patients treated for skin or to extremities. The other surprising finding was that, although patients treated with field sizes greater than 400 cm2 began to vomit within 1-2 days of starting RT, the median time to onset for others was 8 days.. Although the major findings are consistent with general experience and beliefs, (e.g. that upper abdominal fields and large volumes are associated with a high incidence and early onset of emesis), the others are not (e.g. 10% or more average incidence for non-abdominal exposures and an 8-day median development time). Maybe we are not looking carefully enough or maybe there is a placebo effect of keeping a diary to record an event the patients suspect will happen. In any event, the subject is important enough to our patients to warrant further investigation. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC From daemon Mon Aug 23 14:00:00 1999 Received: (from daemon@localhost) by net.bio.net (8.9.1a/8.9.1) id OAA00223; Mon, 23 Aug 1999 14:00:00 -0700 (PDT) To: radoncjc@net.bio.net Reply-To: radoncjc@net.bio.net From: jstaylor@sulmail.stanford.edu Subject: August 1999 Internet Radiation Oncology Journal Club (IROJC) Message-ID: Date: Mon, 23 Aug 1999 13:54:10 -0700 (Pacific Daylight Time) Date: Thu, 05 Aug 1999 10:36:03 -0400 From: Brian Goldsmith Reply-To: briandeb@bellatlantic.net To: bjg@mhpcc.edu Subject: August 1999 Internet Radiation Oncology Journal Club (IROJC) August 1999 Internet Radiation Oncology Journal Club (IROJC) ------------------------------------------------------- Posting of references for review and discussion ------------------------------------------------------- The 51st collection of references suggested for attention and discussion by the IROJC's Board of Editors: Sarah Donaldson, M.D. Editor, Pediatric Radiation Oncology Robert Foote, M.D. Editor, Head and Neck / Skin Radiation Oncology Abram Recht, M.D. Editor, Breast Radiation Oncology Rich Hoppe, M.D. Editor, Reticuloendothelial System Radiation Oncology Dan Petereit, M.D. Editor, Gynecological Radiation Oncology Andrew Turrisi, M.D. Editor, Lung and Mediastinum Radiation Oncology Joel Tepper, M.D. Editor, Gastrointestinal and Soft Tissue Sarcoma Radiation Oncology Mack Roach, M.D. Editor, Genitourinary Radiation Oncology Glenn Bauman, M.D. Ph.D. Editor, Central Nervous System Radiation Oncology Rod Withers, M.D., D.Sc. Editor, Radiobiology Jim Purdy, Ph.D. Editor, Radiation Oncology Physics and Dosimetry ----------------------------------------------------- You're encouraged to critically review this set of references and respond by posting your comments to the IROJC readership at radoncjc@net.bio.net. Comments should be in compliance with IROJC commentary rules (see below). In the month that follows this posting of references, submitted comments will be delivered to the e-mail boxes of the IROJC readership, with the goal of stimulating a professional discussion of these references and their subjects. ------------------------------------------------------------ ARCHIVED IROJC POSTINGS and commentary are available on the World Wide Web! Look for them on http://www.bio.net/ Click on the "Access the BIOSCI/bionet Newsgroups" hyperlink, and then go to "RADIATION-ONCOLOGY/Prototype". Or directly access the RADIATION-ONCOLOGY folder at http://www.bio.net/hypermail/RADIATION-ONCOLOGY/ There's also a freeWAIS search tool at the website, for searching archived postings for keywords or phrases! ------------------------------------------------------------ Commentary Rules: (1) Please cite the subject category in the header of your e-mail message, e.g., Subject: CNS 8/99. (2) Address the readership at large - not the Editor who suggested the reference. The Editor is under no obligation to respond to questions posed by the IROJC readership. (3) The Editor's selection is not necessarily an endorsement of the authors' conclusions. In fact, articles may be selected for criticism. (4) Comments posted to the Internet are public. Professional wording is prudent. (5) Comment only on journal articles that you have read recently, and please keep comments specific. (6) In order to minimize confusion, limit comments to the current month's list of references. (7) Please sign all comments and questions to the IROJC. By identifying yourself, you promote a more collegial and friendly environment! (8) Address to the Moderator (briandeb@bellatlantic.net) private questions and comments which are not intended for IROJC posting and public reading. ****************** Peds: Donaldson 8/99 AU: Relling MV, Rubnitz JE, Rivera GK, Boyett JM, Hancock ML, Felix CA, Kun LE, Walter AW, Evans WE, Pui CH. TI: High incidence of secondary brain tumours after radiotherapy and antimetabolites. SO: Lancet 1999 Jul 3;354(9172):34-9 URL: http://www.thelancet.com/newlancet/sub/issues/vol354no9172/early34.html Abstract: BACKGROUND: Brain tumours rarely occur in survivors of childhood acute lymphoblastic leukaemia after cranial radiotherapy. An unusually high frequency of brain tumours seen among children enrolled in one of our leukaemia treatment protocols, Total Therapy Study XII, prompted us to identify the potential causes of this complication. METHODS: We assessed clinical, biological, and pharmacokinetic features in all 52 children who received prophylactic cranial radiotherapy. We compared the cumulative incidence of brain tumours between subgroups, and with that of 421 children who received radiotherapy in previous studies. FINDINGS: The incidence of brain tumours among irradiated children (six of 52, 12.8% [SE 5.0]) was high compared with patients in the same study who did not receive radiotherapy (none of 101; p equals 0.0008) and with other protocols that included cranial radiotherapy (p<0.0001). Of the six children, four had erythrocyte concentrations of thioguanine nucleotide metabolites higher than the 70th percentile for the entire cohort, and three had a genetic defect in thiopurine catabolism. The 8-year cumulative incidence of brain tumour among children with defective versus wild-type thiopurine methyltransferase phenotype was 42.9% (SE 20.6) versus 8.3% (4.7; p equals 0.0077). This protocol differed from previous protocols, in that more intensive systemic antimetabolite therapy was given before and during radiotherapy. INTERPRETATION: These data support the elimination of prophylactic radiotherapy for acute lymphoblastic leukaemia except in patients at high risk of central-nervous-system relapse. Underlying genetic characteristics and treatment variables may be associated with an increased risk of radiation-associated brain tumours. Editor's comments: In forming my comments, I consulted with Dr. Larry Kun, who is a co-author on this paper and senior author on a prior paper from the same investigators which I recommend you also read as a companion to the Lancet paper. It is: AU: Walter AW, Hancock ML, Pui C-H, Hudson MM. Ochs JS, Rivera GK, Pratt CB, Boyett JM, and Kun LE. TI: Secondary brain tumors in children treated for acute lymphoblastic leukemia at St Jude Children's Research Hospital. SO: J Clin Oncol 16: 3761-3767, 1998 URL: http://www.jco.org/cgi/content/abstract/16/12/3761 It is important to keep in perspective that the overall incidence of post-therapy malignant gliomas in children treated for ALL is 0.5-2% with follow up durations of 10-20 years. When managing children with ALL one must find balance between the efficacy of our treatments and their toxicities - those from irradiation, and those from systemic and intrathecal chemotherapy. When one limits exposure to radiation, then higher doses, and longer durations of chemotherapy are required to treat and/or prevent CNS leukemia. Investigators at St Jude Children's Research Hospital have pioneered a series of carefully planned and conducted clinical trials with aim to decreasing and eliminating CNS leukemia. The Lancet article points to an interesting interaction of antimetabolite exposure with irradiation as co-carcinogens observed in their Total Therapy Study XII. While we usually think of alkylating agents as culprits to secondary malignancies, it is possible that the anti-metabolites also play a broader role than previously recognized. While we all search for the least toxic therapy and respect the clear indications for use of radiotherapy when treating the brain, it is important to note that a recent POG frontline ALL study required closure due to Methotrexate related neurotoxicity. Thus, "More is not necessarily better" with respect to all therapy directed to the central nervous system. ****************** Head/Neck/Skin: Foote 8/99 AU: van Dam FS, Hilgers FJ, Emsbroek G, Touw FI, van As CJ, de Jong N TI: Deterioration of olfaction and gustation as a consequence of total laryngectomy. SO: Laryngoscope 1999 Jul;109(7 Pt 1):1150-5. Abstract: INTRODUCTION: After total laryngectomy the absence of a nasal airflow results in a decrease in olfaction and perception of flavors. MATERIALS AND METHODS: Odor perception was assessed in 63 laryngectomized patients with two different olfactory tests. The methods used by patients to smell were observed during olfactory testing. Patients' judgment about their olfaction and gustation was assessed by means of a structured questionnaire, semistructured interview, and self-rating. RESULTS: Based on the results of the olfactory tests, patients were categorized as "smellers" and "nonsmellers." Approximately one third of the patients were able to smell the odorous substances used in the olfactory tests. The smellers more often used a variety of methods to smell than the nonsmellers (P < .002); in most patients the method consisted of active use of facial muscles. Patients appeared well able to judge their own odor perception. Compared with the smellers, the nonsmellers judged their odor perception as worse (P < .003) and reported a more severe decrease in gustation after the operation (P < .033). The results of this study in laryngectomized patients confirm the interrelation between olfaction and gustation: the nonsmellers reported a poorer gustation and a more severe decrease in gustation and appetite than both the smellers and a reference group of elderly persons (P < .05). Patients who reported a deterioration of olfaction and gustation tended to experience negative consequences such as the inability to smell smoke, leaking gas, or agreeable odors. CONCLUSION: Olfaction and odor-related flavor sensation are seriously deteriorated after total laryngectomy. Editor's comments: Quality of life issues related to total laryngectomy have focused mainly on the loss of a lung powered voice. When physicians were surveyed regarding the major quality of life issues in patients undergoing total laryngectomy, the majority thought it was the loss of laryngeal speech. However, when patients who had undergone a total laryngectomy were surveyed, the most important detriment to their quality of life according to them was the problems associated with having a stoma--inability to blow their nose when they had a cold, severe limitations in showering or swimming, constant mucous production and cough, people staring in public, sexual dysfunction, pulmonary problems, etc. Additional difficulties associated with a stoma are the effects it has on the sense of smell and taste. In this study, olfaction was assessed in patients who had undergone a laryngectomy by means of olfactory tests. Taste and olfaction was assessed by means of a structured questionnaire, semi-structured interview, and self-rating. The influence olfactory and taste problems had on daily life was also assessed. Significant findings included: 68% of the patients were unable to smell. Both those who could still smell and those who could not experienced significant decreases in odor perception, taste and appetite. Additional negative consequences reported by patients included an unsafe feeling in the inability to smell smoke, leaking gas or the burning of food; the absence of pleasant odors; and the impact on hygiene--such as the inability to smell bodily odors. 62% reported significant changes in taste. Negative consequences included changes in dietary habits and the inability to enjoy food (reported by 33%). 57% were not informed preoperatively about the potential for the loss of smell and/or taste. Only 8% received instructions about techniques to improve odor perception during rehabilitation. Some patients had discovered on their own techniques to improve airflow through the nasal cavity in order to improve the sense of smell. Some used facial muscles, neck muscles or jaw movements to induce or create an air stream in the nose through which odorous substances were able to reach the olfactory organ. Pushing and releasing the soft palate from the posterior pharyngeal wall seemed to be effective too. Moving the object to be smelled around the nose was frequently performed to improve smell. Intensive chewing, especially with the mouth closed, and back-and-forth movements of food in the mouth seemed to improve taste. This type of chewing induces an air stream into the oral cavity that can extend backwards into the nasal cavity to stimulate the olfactory organ. These techniques should be formally studied to determine their efficacy. In the interim they can be suggested to patients as ways to improve smell and taste after total laryngectomy. Taste and smell should be included in quality of life assessments in patients with head and neck cancer. ****************** GYN: Petereit 8/99 No Reference Selected ****************** GI / Soft Tissue Sarcoma: Tepper 8/99 No Reference Selected ****************** CNS: Bauman 8/99 AU: Merchant TE, Happersett L, Finlay JL, Leibel SA. TI: Preliminary results of conformal radiation therapy for medulloblastoma. SO: Neuro-Oncology [serial online], Doc. 98-01, June 15, 1999 URL: http://neuro-oncology.mc.duke.edu/neuro-onc/files/issues/present/merchant/index.html Abstract: Radiation therapy for medulloblastoma consists of postoperative irradiation of the intracranial and spinal subarachnoid volume with an additional boost to the primary site of disease in the posterior fossa. The entire posterior fossa is usually included in the boost volume. Conformal radiation therapy techniques may be used to boost the primary site alone and substantially reduce the dose received by normal tissues, including the supratentorial brain, the middle and inner ear, and the hypothalamus. Using these techniques to irradiate only the tumor bed or residual tumor and not the entire posterior fossa represents a new paradigm in the treatment of medulloblastoma. In this study, we examine the use of conformal radiation therapy in the treatment of 14 patients with medulloblastoma. These patients were treated with multiple static, individually shaped, noncoplanar beams directed at the primary site after craniospinal irradiation. Excluding two patients who had previously received irradiation to the posterior fossa, the mean dose delivered to the primary site was 5715 cGy. Among the medulloblastoma patients (n equals 10) who received immediate postoperative radiation therapy, no failures have occurred with a median follow-up of 42 months (range from 30 to 54 months). To demonstrate the differences in the distribution of dose to normal tissues when comparing conventional and conformal techniques, dose-volume histograms of the total brain, middle and inner ear, hypothalamus, and temporal lobe were created and presented for an example case. The neurologic, neuroendocrine, and neurocognitive outcome for patients with medulloblastoma may be influenced with the use of conformal radiation therapy. The use of these techniques should be formally tested in prospective studies of rigorously staged patients with failure rate monitoring. Editor's comments: In this series a small number of patients were treated with conformal radiotherapy to the postoperative tumor bed and imageable residual disease for favourable risk medulloblastoma. Modest dose escalation to a median dose of 57Gy was possible and no failures have been observed after a median followup of 42 months. Potential pitfalls in the treatment of medulloblastoma with radiation have been summarized recently by Halperin (Halperin EC. Impact of radiation technique upon the outcome of treatment for medulloblastoma. Int J Radiat Oncol Biol Phys. 1996 Aug 1;36(1):233-9) and cautions against an abrupt shift away from the posterior fossa boost. Certainly the technique described by Merchant et al is technically demanding. Accurate delineation of the tumor bed and residual disease for the 3D treatment plan and the treatment of multiple unconventional beam angles in a pediatric (read: fidgety) population is not to be undertaken lightly. Nevertheless, the potential lower toxicity of such highly conformal treatments is attractive. The authors call for the prospective evaluation of conformal boosts in clinical trials...the QA of such a trial (especially a multi-institutional trial) will be formidible and will probably require the resources of a 3D ready group like the RTOG. Like the institutions that pioneered the use of lower doses of radiation with chemotherapy for favourable risk medulloblastomas; Merchant et al point the way towards yet another potential method of lowering the late toxicity in a curable malignancy. The cautious introduction (and prospective evaluation) of such smaller volume, conformal or IMRT boosts in medulloblastomas in institutions with expertise in these technically demanding setups should be followed with interest. In the interim, there are some modest gains to be made in lowering toxicity through the use of conformal posterior fossa boosts using posterior wedged pairs. Such boosts are easier to plan, deliver and verify and do spare the auditory apparatus and temporal lobes to a greater extent than the typical lateral opposed pair. Whether one could safely dose escalate to the gross residual disease on top of a conformal posterior fossa boost also remains to be demonstrated. As an aside, this article appears in a new journal "Neuro-Oncology". The inaugural issue of this journal appeared in January 1999 and serves as the journal for the Society for Neuro-Oncology (SNO). The journal is also available online (http://neuro-oncology.mc.duke.edu) and can be accessed without a subscription until at least October 1999 if you would like a preview. Subscriptions for the journal and membership in SNO is also available through this website. The journal seems strong on good review articles, particularly on the molecular genetics of brain tumors, with a growing number of original research articles appearing. The journal would benefit greatly from the support of the radiation oncology community, particularly original article submissions. While I do belong to SNO, I am not on the editorial board for the journal, nor do I get a commission for subscriptions...I just would like to see the journal flourish as the early issues seem very well produced. ****************** Physics/Dosimetry: Purdy 8/99 No Reference Selected ****************** Breast: Recht 8/99 AU: Yamada Y, Ackerman I, Franssen E, MacKenzie RG, Thomas G. TI: Does the dose fractionation schedule influence local control of adjuvant radiotherapy for early stage breast cancer? SO: Int J Radiat Oncol Biol Phys 1999 Apr 1;44(1):99-104. Abstract: PURPOSE: To explore the correlation between dose fractionation and local control for the adjuvant radiotherapy of early stage breast cancer. METHODS AND MATERIALS: A matched-pair analysis of early stage invasive breast cancer treated adjuvantly with two different dose fractionation schedules, 4000 cGy in 16 fractions (Cohort A) vs. 5000 cGy in 25 fractions (Cohort B) was undertaken to compare local control rates. A systematic review of the published experience in similar patient populations was conducted and the reported dose fractionation schedule was converted to a biologic effect dose (BED) based upon the linear quadratic equation. The BED was then used as a basis for comparing reported local control rates with different dose fractionation schemes. RESULTS: The 118 patient pairs were matched from Cohort A and Cohort B using known significant prognostic factors including age, histology, surgical margins, receptor status, lymphvascular space invasion, extensive intraductal disease, lymph node status, and systemic therapy. The local recurrence rate at 5 years for those treated with 4000 cGy (BED equals 65 cGy4) and 5000 cGy (BED equals 75 cGy4) was 12.7% and 6.8%, respectively, and this difference was not statistically significant (p equals 0.09). Overall survival was 84% at 5 years for both groups. Comparison of the different dose fractionation schemes reported in the literature revealed a highly statistically significant difference between those treated with less than a BED of 75 Gy4 and those treated with a BED of 75 Gy4 or greater. CONCLUSION: Although not statistically significant, there was a trend in the matched pair analysis which suggests that 4000 cGy in 16 fractions (BED equals 65 cGy4) provides inferior local control compared to 5000 cGy in 25 fractions (BED equals 75 cGy4). Moreover, the literature review demonstrates that a dose control relationship may exist for local control in the adjuvant setting. A dose fractionation schedule equivalent to 5000 cGy in 25 fractions to the whole breast may represent the optimal dose fractionation schedule for local control. Editor's comments: An important practical question in these days of increasing budgetary stringency in health care is the optimal fractionation and total dose needed to perform a particular job well withan acceptable risk of complications. Those of us who practice in the United States remain somewhat sheltered from this still, but this problem has been a long- standing one for colleagues in Canada and Europe (particularly in the United Kingdom). The current article deals with this problem as it applies to the whole-breast phase of breast-conserving therapy. (The issue of giving a boost or not is another related issue; see my discussion of this in this Journal Club's archives of 5/97, with regards to a randomized trial conducted in Lyon, France; J Clin Oncol 1997;15:963-968; URL: http://www.bio.net/hypermail/RADIATION-ONCOLOGY/9705/0001.html) This important study from the Toronto-Sunnybrook Regional Cancer Centre in Toronto suggests that, in patients treated without a boost, a dose of 50 Gy in 25 fractions results in a substantially lower recurrence rate than 40 Gy in 16 fractions. However, the analysis does not separate results according to margin status or other prognostic factors. Other studies show that patients with negative margins have lower failure rates with similar short-course schemes than were seen here (for example, 5-year failure rate of 6% in a study from British Columbia, Olivotto et al, Radiother Oncol 1996;7-13; and a crude rate of 3.5% (19/541) in a series from the Christie Hospital in Manchester, England, at a median FU of 4.7 years, Magee et al, Clin Oncol 1999;11:40-45; neither group gave a boost). Cosmetic results and complication rates were not reported in the Toronto study, but in the British columbia study these were quite comparable to series using daily doses of 1.8-2 Gy. A cautionary note has been raised by a review of the Ontario Cancer Registry, in which patients with left-sided cancers had a higher cardiac mortality rate (2%) than patients with right-sided cancers (1%); the great majority of patients received 40 Gy in 16 fractions to breast tangents (without an attempt to include the IMNs); Paszat et al, Int J Radiat Oncol Biol Phys 1999;755-761. Randomized trials comparing different fractionation schemes are ongoing in the United Kingdom (the START trial) and Ontario. These will hopefully help settle some of these questions. ****************** RES: Hoppe 8/99 AU: Shipp MA, Abeloff MD, Antman KH, Carroll G, Hagenbeek A, Loeffler M, Montserrat E, Radford JA, Salles G, Schmitz N, Symann M, Armitage JO, Coiffier B, Philip T. TI: International Consensus Conference on high-dose therapy with hematopoietic stem-cell transplantation in aggressive non-Hodgkin's lymphomas: report of the jury. SO: Ann Oncol 1999 Jan;10(1):13-9. Editor's comments: The "Jury" recommended high dose therapy (HDT) for patients with chemosensitive first or subsequent relapse, based upon the PARMA study (see the January 1996 IJROC RES selection: http://www.bio.net/hypermail/RADIATION-ONCOLOGY/9601/0000.html). However, HDT was not recommended for patients in chemorefractory first or subsequent relapse. The data for HDT as a component of initial induction therapy for high risk patients (variably defined) were judged to be inconclusive at this point, and additional studies were recommended. They specifically urged these studies be done for patients in the "high-intermediate" or "high-risk" categories according to the International Prognostic Index (3 or more unfavorable factors). The role of radiation therapy was not addressed in any depth. The absence of randomized studies made it impossible to determine whether TBI-containing regimens were superior to non-TBI regimens. The role of local RT was not discussed, although a significant proportion of patients often have some RT as a component of their high dose therapy (40% in the PARMA study). ****************** Lung/Mediastinum: Turrisi 8/99 AU: Nestle U, Walter K, Schmidt S, Licht N, Nieder C, Motaref B, Hellwig D, Niewald M, Ukena D, Kirsch CM, Sybrecht GW, Schnabel K. TI: 18F-deoxyglucose positron emission tomography (FDG-PET) for the planning of radiotherapy in lung cancer: high impact in patients with atelectasis. SO: Int J Radiat Oncol Biol Phys 1999 Jun 1;44(3):593-7. Abstract: PURPOSE: 18F-deoxyglucose positron emission tomography (FDG-PET) is increasingly applied in the staging of lung cancer (LC). This study analyzes the potential contribution of PET in radiotherapy planning for LC with special respect to tumor-associated atelectasis. METHODS AND MATERIALS: Thirty-four patients with histologically confirmed LC, who had been examined by PET during pretreatment staging, were included. All were irradiated after CT-based therapy planning with anterior/posterior (AP) portals encompassing the primary tumor and the mediastinum (CT portals, CP). The result of the PET examination was unknown in treatment planning. In retrospect, a PET portal (PP) was delineated and compared with the CP. RESULTS: In 12/34 cases, the shape and/or size of the portals were changed, primarily (n equals 10) the size of the fields was reduced. The median area of CP was 182 cm2 versus 167 cm2 of PP. Seventeen of 34 patients had dys- or atelectasis caused by a central primary tumor. In these cases, differences between CP and PP were significantly more frequent than in the other patients (8/17 vs. 3/17, p equals 0.03). CONCLUSION: In this retrospective analysis, the information provided by FDG-PET would have contributed to a substantial reduction of the size of radiotherapy portals. This applies particularly for patients with tumor-associated dys- or atelectasis. Editor's comments: PET's are the new high technology on the block. Many centers, including my own, have access only at a distance. There are increasing reports of use and Medicare now pays for diagnostic evaluation in lung cancer. However, we send our patients 3 - 5 hours away (Charlotte or Durham) in order to get diagnostic information. Recent information says these studies help in diagnosing nodules, lymph nodes and that intensity of uptake may correlate with response and survival. The captioned paper looks at another issue: Can PET help define target volumes. This study emphasizes a role in distinguishing atelectasis from tumor. We also want to use it to define who has high risk of "size-occult" nodes. For particularly the medically inoperable patient, but also perhaps others, routine treatment of mediastinal and certainly supraclavicular nodes may not be mandatory any longer. Targeting tissues that "glow" in PET Scanners may reduce the target and ensuing toxicity. However, trials are needed to prove that there is not a substantial downside (compromise in survival or local control)if different, smaller, lesser normal tissue inclusive volume targets are selected for treatment. The PET may be a useful tool. As in all technologies, there may be a wave of rabid enthusiasm, followed by a valley of disappointment when false positives and negatives are discovered. This paper describes a wise use of this technology -- good luck to those of you that have it, and good wishes for those of us that don't. ****************** GU: Roach 8/99 No Reference Selected ****************** Radiobiology: Withers 8/99 TI: Radiation-induced emesis: a prospective observational multicenter Italian trial. The Italian Group for Antiemetic Research in Radiotherapy. SO: Int J Radiat Oncol Biol Phys 1999 Jun 1;44(3):619-25. Abstract: PURPOSE: A prospective observational multicenter trial was carried out to assess the incidence, pattern, and prognostic factors of radiation-induced emesis (RIE), and evaluate the use of antiemetic drugs in radiation oncology clinical practice. METHODS AND MATERIALS: Fifty-one Italian radiation oncology centers took part in this trial. The accrual lasted 2 consecutive weeks, only patients starting radiotherapy in this period were enrolled. Exclusion criteria were age under 18 years, and concomitant chemotherapy. Evaluation was based on diary cards filled in daily by patients during radiotherapy and 1 week after stopping it. Diary cards recorded the intensity of nausea and any episode of vomiting and retching. Prophylactic and symptomatic antiemetic drug prescriptions were also registered. RESULTS: Nine hundred thirty-four patients entered the trial, and 914 were evaluable. Irradiated sites were: breast in 211 patients, pelvis in 210 patients, head and neck in 136 patients, thorax in 129 patients, brain in 52 patients, upper abdomen in 42 patients, skin and/or extremities in 37 patients, and other sites in 97 patients. Vomiting and nausea occurred in 17.1% and 37.3% of patients, respectively, and 38.7 % patients had both vomiting and nausea. At multifactorial analysis, the only patient-related risk factor that was statistically significant was represented by previous experience with cancer chemotherapy. Moreover, two radiotherapy (RT)-related factors were significant risk factors for RIE, the irradiated site and field size. In fact, a statistically significant higher percentage of RIE was registered in upper abdomen RT and RT fields > 400 cm2. Although nonstatistically significant, patients receiving RT to the thorax and head and neck presented a higher incidence of RIE. Only a minority (14%) of patients receiving RT were given an antiemetic drug, and the prescriptions were more often symptomatic than prophylactic (9% vs. 5%, respectively). Different compounds and a wide range of doses and schedules were used; however, there is some evidence from our data that in spite of antiemetic prophylaxis, 46% of patients had vomiting, and 58% had nausea. The majority (93%) of the prophylactic group received oral 5-hydroxytriptamine receptor (5-HT3) antagonist (8 mg/day, 7 days/week). In the symptomatic group, 54% and 41% patients received 5-HT3 antagonists and metoclopramide, respectively. At multivariate analysis, no patient- or RT-related risk factor for RIE was found to influence significantly the prophylactic or symptomatic use of antiemetics. CONCLUSION: Our study provided useful data on epidemiology and characteristics of RIE. Previous chemotherapy, field size, and irradiated site (upper abdomen) were the only significant prognostic factors of RIE. A remarkable incidence of RIE was found in patients submitted to thoracic and head and neck RT. With this background of knowledge, it will be possible to better plan further studies on this important problem. Moreover, the low rate of antiemetics use and the wide variety of doses and schedules employed suggest the need to reinforce the "evidence based" approach to identify the best antiemetic approach to RIE. Editor's comments: This study reports on nausea and vomiting among more than 900 patients beginning radiation therapy in 51 centers in Italy over a 2-week period in 1996. Each patient kept a diary of their nausea and vomiting (including retching). Not surprising is the result of a multifactorial analysis which shows upper abdominal and large field irradiation to be risk factors. What is surprising is the high incidence recorded in patients being treated to other areas than upper abdomen. This was particularly so for thorax and head and neck (with incidences of 26% and 18%, respectively, but was also reported by, for example, 10% of patients treated for skin or to extremities. The other surprising finding was that, although patients treated with field sizes greater than 400 cm2 began to vomit within 1-2 days of starting RT, the median time to onset for others was 8 days.. Although the major findings are consistent with general experience and beliefs, (e.g. that upper abdominal fields and large volumes are associated with a high incidence and early onset of emesis), the others are not (e.g. 10% or more average incidence for non-abdominal exposures and an 8-day median development time). Maybe we are not looking carefully enough or maybe there is a placebo effect of keeping a diary to record an event the patients suspect will happen. In any event, the subject is important enough to our patients to warrant further investigation. ****************** Brian J. Goldsmith, M.D. Moderator, IROJC