Conventional radiotherapy versus concurrent chemoradiotherapy versus accelerated radiotherapy in locoregionally advanced carcinoma of head and neck: Results of a prospective randomized trial

Ghosh‐Laskar, Sarbani; Kalyani, N.; Gupta, Tejpal; Budrukkar, Ashwini; Murthy, Vedang; Sengar, Manju; Chaukar, Devendra; Pai, Prathamesh; Chaturvedi, Pankaj; D’Cruz, Anil; Agarwal, Jitendra

doi:10.1002/hed.23865

Cited by 53 publications

(44 citation statements)

References 13 publications

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“…The control group of a four-arm trial 4 was triplicated (ie, data for patients in the control group were copied twice to have three control arms to compare with each experimental arm), a 2 × 2 trial (EORTC 22962 45 ) included three relevant comparisons for the meta-analysis, and three three-arm trials 36,37,55 included two relevant comparisons. The 33 trials included in the analysis of fractionation schedules (comparison 1) were divided into four predefined subgroups, depending on the type of radiotherapy: hyperfractionation (eight comparisons, including the unpublished EORTC 22962 trial), 4,33,44,45,49,50,56 moderately accelerated radiotherapy (19 comparisons), 2,4,30,32,34–39,41,42,46,54,55,57–59 very accelerated radiotherapy (seven comparisons, including the unpublished CHARTWEL trial), 3,47,51–53,60 and moderately hypofractionated (dose per fraction between 2–2·5 Gy [two comparisons]; 31,40 appendix pp 17–18).…”

Section: Resultsmentioning

confidence: 99%

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

Lacas

Bourhis

Overgaard

et al. 2017

The Lancet Oncology

262

177

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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updated meta-analysis, we searched bibliography databases, trials registries, and meeting proceedings for published or unpublished randomised trials done between Jan 1, 2009, and July 15, 2015, comparing primary or postoperative conventional fractionation radiotherapy versus altered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 up...

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Section: Resultsmentioning

confidence: 99%

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

Lacas

Bourhis

Overgaard

et al. 2017

The Lancet Oncology

262

177

View full text Add to dashboard Cite

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“…Groupe d'Oncologie Radiotherapie Tete et Cou (GORTEC 99-02) [22] was the largest study included in the meta-analysis. Data from a previously reported abstract were extracted initially in brief and subsequently updated through personal communication and a full-text publication [23]. Two other studies [24,25] using a non-inferiority design for comparing CCRT with concomitant boost radiotherapy (CBRT) were also included.…”

Section: Resultsmentioning

confidence: 99%

“…The AFRT schedules that were used in the studies were also heterogeneous. Although one trial used a split-course AFRT schedule [21], two used two different forms of acceleration [22,23] and the remaining two used the CBRT regimen [24,25]. None of the included studies used HFRT as altered fractionation that had shown the maximal benefit among all AFRT schedules in the MARCH metaanalysis [12,13].…”

Section: Discussionmentioning

confidence: 98%

“…The point estimate for grade 2 or worse xerostomia (b) also favours AFRT, but is statistically non-significant as its 95% confidence interval straddles the line of unity. combination chemotherapy comprising carboplatin and 5-flourouracil [21,22,24] concurrently during radiotherapy, whereas the other two trials used single agent cisplatin (weekly [23] and 3 weekly [25], respectively) as concurrent chemotherapy. The AFRT schedules that were used in the studies were also heterogeneous.…”

Section: Discussionmentioning

confidence: 99%

“…At a median follow-up of 5.2 years, there was a significant difference in locoregional control (P ¼ 0.045), progression-free survival (P ¼ 0.041) and overall survival (P ¼ 0.040) favouring conventionally fractionated CCRT compared with AXRT alone. In another three-arm study [23], 186 patients with locoregionally advanced non-nasopharyngeal head and neck cancers were randomly assigned to conventionally fractionated radiotherapy alone, conventionally fractionated CCRT or AXRT alone. At a median follow-up of 48 months for survivors, the 5 year locoregional control (49% versus 27%, P ¼ 0.01) and disease-free survival (39% versus 20%, P ¼ 0.03) were significantly better with CCRT compared with AXRT alone.…”

Section: Description Of Included Studiesmentioning

confidence: 99%

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Systematic Review and Meta-analysis of Conventionally Fractionated Concurrent Chemoradiotherapy versus Altered Fractionation Radiotherapy Alone in the Definitive Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

et al. 2016

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A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer

Patil

Noronha

Joshi

et al. 2019

Cancer

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BACKGROUND:Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This openlabel, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m 2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT). The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m 2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT. Cancer 2019;125:3184-3197.

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Conventional radiotherapy versus concurrent chemoradiotherapy versus accelerated radiotherapy in locoregionally advanced carcinoma of head and neck: Results of a prospective randomized trial

Abstract: CRT is associated with significantly better locoregional control as compared to RT and accelerated RT with higher but acceptable acute and late toxicities.

Cited by 53 publications

References 13 publications

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

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

Systematic Review and Meta-analysis of Conventionally Fractionated Concurrent Chemoradiotherapy versus Altered Fractionation Radiotherapy Alone in the Definitive Management of Locoregionally Advanced Head and Neck Squamous Cell Carcinoma

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer

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