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Role of radiotherapy fractionation in head and neck cancers (MARCH): an updated meta-analysis

Lacas, Benjamin,Bourhis, Jean,Overgaard, Jens,Zhang, Qiang,Gré,goire, Vincent,Nankivell, Matthew,Zackrisson, Bjö,rn,Szutkowski, Zbigniew,Suwiń,ski, Rafał,Poulsen, Michael,O'Sullivan, Br Elsevier 2017 The Lancet. Oncology Vol.18 No.9
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Summary Background The Meta-Analysis of Radiotherapy in squamous cell Carcinomas of Head and neck (MARCH) showed that altered fractionation radiotherapy is associated with improved overall and progression-free survival compared with conventional radiotherapy, with hyperfractionated radiotherapy showing the greatest benefit. This update aims to confirm and explain the superiority of hyperfractionated radiotherapy over other altered fractionation radiotherapy regimens and to assess the benefit of altered fractionation within the context of concomitant chemotherapy with the inclusion of new trials. Methods For this updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered fractionation radiotherapy (comparison 1) or conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone (comparison 2). Eligible trials had to start randomisation on or after Jan 1, 1970, and completed accrual before Dec 31, 2010; had to have been randomised in a way that precluded prior knowledge of treatment assignment; and had to include patients with non-metastatic squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx undergoing first-line curative treatment. Trials including a non-conventional radiotherapy control group, investigating hypofractionated radiotherapy, or including mostly nasopharyngeal carcinomas were excluded. Trials were grouped in three types of altered fractionation: hyperfractionated, moderately accelerated, and very accelerated. Individual patient data were collected and combined with a fixed-effects model based on the intention-to-treat principle. The primary endpoint was overall survival. Findings Comparison 1 (conventional fractionation radiotherapy vs altered fractionation radiotherapy) included 33 trials and 11 423 patients. Altered fractionation radiotherapy was associated with a significant benefit on overall survival (hazard ratio [HR] 0·94, 95% CI 0·90–0·98; p=0·0033), with an absolute difference at 5 years of 3·1% (95% CI 1·3–4·9) and at 10 years of 1·2% (−0·8 to 3·2). We found a significant interaction (p=0·051) between type of fractionation and treatment effect, the overall survival benefit being restricted to the hyperfractionated group (HR 0·83, 0·74–0·92), with absolute differences at 5 years of 8·1% (3·4 to 12·8) and at 10 years of 3·9% (−0·6 to 8·4). Comparison 2 (conventional fractionation radiotherapy plus concomitant chemotherapy versus altered fractionation radiotherapy alone) included five trials and 986 patients. Overall survival was significantly worse with altered fractionation radiotherapy compared with concomitant chemoradiotherapy (HR 1·22, 1·05–1·42; p=0·0098), with absolute differences at 5 years of −5·8% (−11·9 to 0·3) and at 10 years of −5·1% (−13·0 to 2·8). Interpretation This update confirms, with more patients and a longer follow-up than the first version of MARCH, that hyperfractionated radiotherapy is, along with concomitant chemoradiotherapy, a standard of care for the treatment of locally advanced head and neck squamous cell cancers. The comparison between hyperfractionated radiotherapy and concomitant chemoradiotherapy remains to be specifically tested. Funding Institut National du Cancer; and Ligue Nationale Contre le Cancer.
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THE BRIGHTEST YOUNG STAR CLUSTERS IN NGC 5253

Calzetti, D.,Johnson, K. E.,Adamo, A.,Gallagher III, J. S.,Andrews, J. E.,Smith, L. J.,Clayton, G. C.,Lee, J. C.,Sabbi, E.,Ubeda, L.,Kim, H.,Ryon, J. E.,Thilker, D.,Bright, S. N.,Zackrisson, E.,Kennic IOP Publishing 2015 The Astrophysical journal Vol.811 No.2
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The nearby dwarf starburst galaxy NGC 5253 hosts a number of young, massive star clusters, the two youngest of which are centrally concentrated and surrounded by thermal radio emission (the 'radio nebula'). To investigate the role of these clusters in the starburst energetics, we combine new and archival Hubble Space Telescope images of NGC 5253 with wavelength coverage from 1500 angstrom 1.9 mu m in 13 filters. These include H alpha, P beta, and P alpha, and the imaging from the Hubble Treasury Program LEGUS (Legacy Extragalactic UV Survey). The extraordinarily well-sampled spectral energy distributions enable modeling with unprecedented accuracy the ages, masses, and extinctions of the nine optically brightest clusters (M-V < -8.8) and the two young radio nebula clusters. The clusters have ages similar to 1-15 Myr and masses similar to 1 x 10(4)-2.5 x 10(5) M-circle dot. The clusters' spatial location and ages indicate that star formation has become more concentrated toward the radio nebula over the last similar to 15 Myr. The most massive cluster is in the radio nebula; with a mass similar to 2.5 x 10(5) M-circle dot and an age similar to 1 Myr, it is 2-4 times less massive and younger than previously estimated. It is within a dust cloud with AV similar to 50 mag, and shows a clear near-IR excess, likely from hot dust. The second radio nebula cluster is also similar to 1 Myr old, confirming the extreme youth of the starburst region. These two clusters account for about half of the ionizing photon rate in the radio nebula, and will eventually supply about 2/3 of the mechanical energy in present-day shocks. Additional sources are required to supply the remaining ionizing radiation, and may include very massive stars.

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