A meta-analysis of hyperfractionated and accelerated radiotherapy and combined chemotherapy and radiotherapy regimens in unresected locally advanced squamous cell carcinoma of the head and neck

BACKGROUND: Former meta-analyses have shown a survival benefit for the addition of chemotherapy (CHX) to radiotherapy (RT) and to some extent also for the use of hyperfractionated radiation therapy (HFRT) and accelerated radiation therapy (AFRT) in locally advanced squamous cell carcinoma (SCC) of the head and neck. However, the publication of new studies and the fact that many older studies that were included in these former meta-analyses used obsolete radiation doses, CHX schedules or study designs prompted us to carry out a new analysis using strict inclusion criteria. METHODS: Randomised trials testing curatively intended RT (≥60 Gy in >4 weeks/>50 Gy in <4 weeks) on SCC of the oral cavity, oropharynx, hypopharynx, and larynx published as full paper or in abstract form between 1975 and 2003 were eligible. Trials comparing RT alone with concurrent or alternating chemoradiation (5-fluorouracil (5-FU), cisplatin, carboplatin, mitomycin C) were analyzed according to the employed radiation schedule and the used CHX regimen. Studies comparing conventionally fractionated radiotherapy (CFRT) with either HFRT or AFRT without CHX were separately examined. End point of the meta-analysis was overall survival. RESULTS: Thirty-two trials with a total of 10 225 patients were included into the meta-analysis. An overall survival benefit of 12.0 months was observed for the addition of simultaneous CHX to either CFRT or HFRT/AFRT (p < 0.001). Separate analyses by cytostatic drug indicate a prolongation of survival of 24.0 months, 16.8 months, 6.7 months, and 4.0 months, respectively, for the simultaneous administration of 5-FU, cisplatin-based, carboplatin-based, and mitomycin C-based CHX to RT (each p < 0.01). Whereas no significant gain in overall survival was observed for AFRT in comparison to CFRT, a substantial prolongation of median survival (14.2 months, p < 0.001) was seen for HFRT compared to CFRT (both without CHX). CONCLUSION: RT combined with simultaneous 5-FU, cisplatin, carboplatin, and mitomycin C as single drug or combinations of 5-FU with one of the other drugs results in a large survival advantage irrespective the employed radiation schedule. If radiation therapy is used as single modality, hyperfractionation leads to a significant improvement of overall survival. Accelerated radiation therapy alone, especially when given as split course radiation schedule or extremely accelerated treatments with decreased total dose, does not increase overall survival

Introducing a new ICRU report: Prescribing, recording and reporting electron beam therapy

The ICRU published several Reports about volumes and doses specifications for radiotherapy, such as the Report 29 (1978), devoted to photon and electron beam therapy. This report 29 becoming absolete, a new Report was published in 1993 for external photon beam radiotherapy, the Report 50, recommending new definitions and more accurate specifications. With electran beams specific problems are raised, and the ICRU considered suitable to prepare a special Report for them, to be published in the near future.The main features of the present draft are as follows:1.Volumes specifications in agreement with the ICRU Report 50,•Volumes to be determined before treatment planning: gross tumour volume (GTV), c1inical target volume (CTV), organs at risk volumes (OR).•Volume to be determined during treatment planning: Planning target volume (PTV).•Volumes resulting fram the treatment plan chosen: treatment volume (TV), irradiated volume (IV).In the future Report on electron beams, an additional volume is defined, the internal target volume (ITV) geometrical concept representing the volume en-compassing the c1inical target volume, taking into consideration margins due to the variations of the clinical target volume in position, shape an size. A similar concept has been extended to organs at risk, the planning organ at risk volume.2.Dose specificationThe general statements for photon beams apply:•dose at a reference point (ICRU point) situated at or near the center of the planning target volume and, when possible, near or on the central axis of the electron beam at the depth of the peak dose.•Minimal and maximal doses in the planning target volume•Dose delivered to the organs at risk•Additional information is recommended, when possible (e.g. DVH).With electron beams, the dose homogeneity expected within the PTV (± 5 to ± 10 %) requires an adaptation of the terapeutic range concept, such that the value of the isodose surface encompassing the PTV be situated between 85 % and 95 % of the reference dose. The peak absorbed dose on the beam axis should always been specified, even if it is different fram the reference dose.At last, as in Report 50, three levels of dose evaluation for reporting are considered, depending on the aim of the treatment and the data available

A prospective investigation of swallowing, nutrition, and patient-rated functional impact following altered fractionation radiotherapy with concomitant boost for oropharyngeal cancer

Altered fractionation radiotherapy for head and neck cancer has been associated with improved locoregional control, overall survival, and heightened toxicity compared with conventional treatment. Swallowing, nutrition, and patient-perceived function for altered fractionation radiotherapy with concomitant boost (AFRT-CB) for T1–T3 oropharyngeal squamous cell carcinoma (SCC) have not been previously reported. Fourteen consecutive patients treated with AFRT-CB for oropharyngeal SCC were recruited from November 2006 to August 2009 in a tertiary hospital in Brisbane, Australia. Swallowing, nutrition, and patient-perceived functional impact assessments were conducted pretreatment, at 4–6 weeks post-treatment, and at 6 months post-treatment. Deterioration from pretreatment to 4–6 weeks post-treatment in swallowing, nutrition, and functional impact was evident, likely due to the heightened toxicity associated with AFRT-CB. There was significant improvement at 6 months post-treatment in functional swallowing, nutritional status, patient-perceived swallowing, and overall function, consistent with recovery from acute toxicity. However, weight and patient perception of physical function and side effects remained significantly worse than pretreatment scores. The ongoing deficits related to weight and patient-perceived outcomes at 6 months revealed that this treatment has a long-term impact on function possibly related to the chronic effects of AFRT-CB

Concomitant cisplatin and radiotherapy in a conventional and modified fractionation schedule in locally advanced head and neck cancer: A randomised phase II EORTC trial

A randomised phase II trial was initiated to explore the feasibility of concomitant cisplatin and radiotherapy with conventional fractionation (CF) or multiple fractions per day (MFD) for patients with locally advanced head and neck malignancies. The MFD schedule was designed to achieve higher tumour concentrations of cisplatin at the time of irradiation by reducing the number of radiation treatment weeks from 7 to 3, allowing recovery from side-effects of both irradiation and cystostatic drugs during the rest periods, while keeping the same total dose and overall treatment time. Patients were randomised between a conventional fractionation scheme (CF) of 70 Gy in 7 weeks with 2 Gy per fraction with a daily dose of 6 mg/m(2) cisplatin and a modified fractionation scheme (MFD) delivering three fractions of 1.6 Gy per day, in weeks 1, 4 and 7, keeping the same overall treatment time and total dose. In the modified treatment regime, a daily dose of 10 mg/m2 cisplatin was administered. 53 patients were entered in this trial and radiotherapy was given according to the schedule to all patients in both treatment arms. Cisplatin was given during the whole course of radiotherapy to only one quarter of the patients in the CF arm, stopping mostly after 5-6 weeks due to bone marrow depression and kidney toxicity, while patients in the MFD arm received it according to schedule. No difference was observed in acute and late toxicity in both treatment arms, while a similar or even better tumour response was obtained with MFD. A 67% higher daily dose of cisplatin concomitant with irradiation could be given in a 3-week multiple fractionation per day schedule, as opposed to the cisplatin given in the conventional daily fractionation schedule of 7 weeks with the same total radiation dose. Similar acute and late toxicities were seen in both treatment arms. (C) 2002 Elsevier Science Ltd. All rights reserved

The influence of the use of CT-planning on the irradiated boost volume in breast conserving treatment.

Item does not contain fulltextBACKGROUND AND PURPOSE: The purpose of this study was to investigate the effect of CT-based delineation and planning on the irradiated boost volume. For this specific purpose we used the data as derived from 2 prospective phase III randomised trials. PATIENTS AND METHODS: Data from 1331 patients (<or=50 years) were analyzed with a reported boost volume from a simulation-based treatment plan (EORTC boost vs no boost trial, n=922), and a CT-scan-based treatment plan (Young Boost Trial, n=409) group. Tumour diameter, irradiation technique (photons vs electrons), lumpectomy size, and age were used as covariates. RESULTS: Median V(95%) in the conventional simulation-based treatment plans was 99 cc (range 9-628) for photons and was 98 cc (13-651) for electrons, whereas in the CT-planned patients, these figures were 178 cc (37-2699) and 150 cc (43-1272), respectively. Multivariable analysis showed an association of the irradiated boost volume with tumour size (p<0.0067), lumpectomy size (p<0.0002), and boost technique (p<0.0004). The use of a CT-scan for volume delineation and treatment planning remained significant (p<0.0001). CONCLUSIONS: The use of a CT-scan for delineation and treatment planning led to a significant increase of the irradiated boost volume by a factor of 1.5-1.8, compared to conventional simulator-based plans

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

ARCON: Accelerated radioterapy with carbogen and nicotinamide in non small cell lung cancer: a phase I/II study by the EORTC

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