No age limit for radical radiotherapy in head and neck tumours

The elderly are often treated less aggressively in an attempt to preserve their quality of Life with regards to toxicity. However, there are few data regarding the acute and late toxicity of radiotherapy (RT) in elderly patients. From February 1980 to March 1995, 1589 patients with head and neck cancers who enrolled in EORTC trials received RT and were available for analysis on RT toxicity. Patients over 65 years of age were in excess of 20%. Data regarding age and acute objective mucosal reactions were available for 1307 patients and 1288 had toxicity greater than or equal to grade 1. Age and acute functional mucosal reactions were registered for 838 patients and 824 patients had toxicity greater than or equal to grade 1. Bodyweight alteration during treatment was available in 1252 patients; it increased in 153 patients and decreased in 1099 patients. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first- and second-line treatments. 749 patients were available for analysis of which 646 had late toxicity grade greater than or equal to 1. Survival and toxicity were examined in different age ranges from 50 to 75 years and over. There was no significant difference in survival between each age group. A trend test was performed to assess any correlation between age and the acute occurring toxicity. There was no significant difference in acute objective mucosal reactions (P = 0.1) and in weight loss > 10% (P = 0.441). In contrast, older patients had more severe (grade 3 and 4) functional acute toxicity (P < 0.001) than younger patients. We evaluated the probability of late toxicity occurrence in relation to time with the Kaplan-Meier method and the logrank test in each age group. Eighteen per cent of patients were free of late effects at 5 years, the logrank test showing no significant difference between ages (P = 0.84). In conclusion, chronological age is irrelevant for therapeutic decisions. Copyright (C) 1996 Elsevier Science Lt

Selection of Large and Objectively Measurable Target Lesions in Eortc Phase-ii Trials - Impact On Recruitment and Response Rate

The EORTC has recently issued minimum requirements for target lesions in phase II trials, aiming at a decrease in measurement errors [minimum size, computer tomography (CT) scan or ultrasound for deep lesions]. Their impact on recruitment and response has been retrospectively studied in a trial of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG), investigating high-dose chemotherapy in patients with advanced soft tissue sarcoma, where 46/103 objective responses were seen, including 10 complete responses. For the 20 patients who did not satisfy the criteria, a similar objective response rate and a significantly higher complete response rate were reported. Among 265 target lesions, the same trends were observed when comparing small to large lesions, for different tumour sites. For deep lesions clinically assessed, significantly higher response rates were reported than for those measured by CT scans or ultrasound. The new stricter EORTC criteria improve the reliability of measurements and have been adopted for future phase II trials of the STBSG. This will not result in the selection of potentially poor responders. Less than 20% of the present recruitment will be lost

Eortc Guidelines for Writing Protocols for Clinical-trials of Radiotherapy

The concept of a Master Protocol for phase III studies was raised at the Steering Committee of the EORTC Radiotherapy Group, in order to make the work of the study coordinators easier, when writing protocols and to give them more homogeneity. The Master Protocol defines and clarifies in a logical order the different steps which must be taken when designing a randomized trial - from the rationale to the references. It pays particular attention to eligibility criteria, volumes of interest defined in agreement with ICRU Report 50 (gross tumor volume, clinical target volume, planning target volume and organs at risk), simulation procedure, treatment technique, normal tissue sparing, dose computation, equipment, dose specification (also in agreement with ICRU Report 50). Last but not least, the different procedures of quality assurance for protocols and patients are also defined (site visits, dummy run procedure, in vivo dosimetry, individual case review) to allow working plans to be made in advance. We are aware that this work is not exhaustive, but hope that the contents will be of help to those who are writing a protocol

[Design, handling, and analysis of a randomised trial.]

Before a newly developed treatment starts being used in practice it must pass through three clinical trial steps, called phase I, II, and III. the subject of this presentation are the phase III clinical trials. Their goal is to compare the treatment under study to the currently standard treatment (either to show the superiority of the new treatment, either to show it is equivalent in terms of efficacy with the standard one). The only way of ensuring a valid comparison is to perform a randomised clinical trial, meaning that for each patient the treatment is assigned randomly be a mechanism unknown by the investigator(s). Each clinical trial must start with the creation of a protocol. The protocol is a document that describes in details all the aspects of performing the trial. Normally, once the first patient is registered into the trial, the protocol shouldn't be modified any more. That's why it must forsee every problem that might show up during the trial, which makes it a difficult task. A crucial question which has to be answered before the trial begins is the 'sample size'-the number of patients needed. This number is based on several parameter. A bad choice of one of these parameters can completely compromise a trial. All data handling and administrative tasks ar usually handled by data manages. They have a crucial role in collecting and validating all the data, and the quality of the whole clinical trial is closely related to the quality of their work. To help them in their tasks, a suitable computer system can be of invaluable help. One of the last steps of the trial is the statistical analysis itself. the statistical tests to be used must be predefined in the protocol and depend mainly on the ene points used for assessing the efficacy. to avoid all bias the analyses must be done using the 'intent to treat' principle. Many problems can show up during the trial: ineligible patients or last to follow up, protocol violations, etc. A well written and well respected protocol should help reducing this list to a minimum. Finally, all this work will only be useful if the results are widely presented in a clear and pertinent way. If the medical community is not convinced by the results, all those resources would have been wasted

Efficacy of 4 Different Regimens in 64 Mantle-cell Lymphoma Cases - Clinicopathological Comparison With 498 Other Non-hodgkins-lymphoma Subtypes

Purpose: Before recognizing mantle-cell lymphoma (MCL) as a distinct entity, these patients were grouped into low-grade (LG) or intermediate-/high-grade categories (IGHG) according to the Working Formulation and received various therapies. This was a unique opportunity to evaluate characteristics, behavior, response to treatment, and outcome of patients with MCL from two phase III trials conducted by the European Organization for the Research and Treatment of Cancer (EORTC): EORTC 20855 IGHG and EORTC 20856 LG. Patients and Methods: After histologic review, 64 diagnosed MCL patients (29 IGHG and 35 LG) were compared with other patients in their respective trials. In the IGHG group, patients received cyclophosphamide, doxorubicin, teniposide (VM(26)), prednisone, vincristine, and bleomycin (CHVmP-VB) or modified doxorubicin, cyclophosphamide, etoposide (VP16), mechlorethamine, vincristine, procarbazine, and prednisone (ProMACE-MOPP). in the LG group, after receiving cyclophosphamide, vincristine, and prednisone (CVP) induction, patients were randomized between maintenance treatment with interferon alfa-2a (IFN) or no further treatment. Results: MCL patients compared with IGHG subtypes showed a similar overall survival and response rate, but shorter duration of response and progression-free survival. Comparing with LG patients, their response rate, duration of response, and progression-free survival showed no difference, while their overall survival wets nearly twice shorter. MCL patients treated with CHVmP-VB had the longest survival. No treatment showed any significant improvement in terms of progression-free survival. Conclusion: These data confirm that MCL represents a clinicopathologic entity, In terms of survival, it behaves like IGHG subtypes, while in terms of progression-free survival, it behaves like LG lymphoma. It is still not clear which first line treatment offers patients with MCL the best chance to obtain both a complete response (CR) and a long-term survival. (C) 1995 by American Society of Clinical Oncology