Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group

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Abstract

Performing intensity-modulated radiotherapy (IMRT) on head and neck cancer patients (HNCPs) requires robust training and experience. Thus, in 2011, the Head and Neck Cancer Working Group (HNCWG) of the Italian Association of Radiation Oncology (AIRO) organized a study group with the aim to run a literature review to outline clinical practice recommendations, to suggest technical solutions and to advise target volumes and doses selection for head and neck cancer IMRT. The main purpose was therefore to standardize the technical approach of radiation oncologists in this context. The following paper describes the results of this working group. Volumes, techniques/strategies and dosage were summarized for each head-and-neck site and subsite according to international guidelines or after reaching a consensus in case of weak literature evidence.

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Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

Christopher Nutting, James Morden, Kevin J. Harrington … (2011)

Summary Background Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia. Methods We undertook a randomised controlled trial between Jan 21, 2003, and Dec 7, 2007, that compared conventional radiotherapy (control) with parotid-sparing IMRT. We randomly assigned patients with histologically confirmed pharyngeal squamous-cell carcinoma (T1–4, N0–3, M0) at six UK radiotherapy centres between the two radiotherapy techniques (1:1 ratio). A dose of 60 or 65 Gy was prescribed in 30 daily fractions given Monday to Friday. Treatment was not masked. Randomisation was by computer-generated permuted blocks and was stratified by centre and tumour site. Our primary endpoint was the proportion of patients with grade 2 or worse xerostomia at 12 months, as assessed by the Late Effects of Normal Tissue (LENT SOMA) scale. Analyses were done on an intention-to-treat basis, with all patients who had assessments included. Long-term follow-up of patients is ongoing. This study is registered with the International Standard Randomised Controlled Trial register, number ISRCTN48243537. Findings 47 patients were assigned to each treatment arm. Median follow-up was 44·0 months (IQR 30·0–59·7). Six patients from each group died before 12 months and seven patients from the conventional radiotherapy and two from the IMRT group were not assessed at 12 months. At 12 months xerostomia side-effects were reported in 73 of 82 alive patients; grade 2 or worse xerostomia at 12 months was significantly lower in the IMRT group than in the conventional radiotherapy group (25 [74%; 95% CI 56–87] of 34 patients given conventional radiotherapy vs 15 [38%; 23–55] of 39 given IMRT, p=0·0027). The only recorded acute adverse event of grade 2 or worse that differed significantly between the treatment groups was fatigue, which was more prevalent in the IMRT group (18 [41%; 99% CI 23–61] of 44 patients given conventional radiotherapy vs 35 [74%; 55–89] of 47 given IMRT, p=0·0015). At 24 months, grade 2 or worse xerostomia was significantly less common with IMRT than with conventional radiotherapy (20 [83%; 95% CI 63–95] of 24 patients given conventional radiotherapy vs nine [29%; 14–48] of 31 given IMRT; p<0·0001). At 12 and 24 months, significant benefits were seen in recovery of saliva secretion with IMRT compared with conventional radiotherapy, as were clinically significant improvements in dry-mouth-specific and global quality of life scores. At 24 months, no significant differences were seen between randomised groups in non-xerostomia late toxicities, locoregional control, or overall survival. Interpretation Sparing the parotid glands with IMRT significantly reduces the incidence of xerostomia and leads to recovery of saliva secretion and improvements in associated quality of life, and thus strongly supports a role for IMRT in squamous-cell carcinoma of the head and neck. Funding Cancer Research UK (CRUK/03/005).

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Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

Arlene Forastiere, Qiang Zhang, Randal Weber … (2013)

To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

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Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.

Jean Bourhis, Jens Overgaard, Hélène Audry … (2006)

Several trials have studied the role of unconventional fractionated radiotherapy in head and neck squamous cell carcinoma, but the effect of such treatment on survival is not clear. The aim of this meta-analysis was to assess whether this type of radiotherapy could improve survival. Randomised trials comparing conventional radiotherapy with hyperfractionated or accelerated radiotherapy, or both, in patients with non-metastatic HNSCC were identified and updated individual patient data were obtained. Overall survival was the main endpoint. Trials were grouped in three pre-specified categories: hyperfractionated, accelerated, and accelerated with total dose reduction. 15 trials with 6515 patients were included. The median follow-up was 6 years. Tumours sites were mostly oropharynx and larynx; 5221 (74%) patients had stage III-IV disease (International Union Against Cancer, 1987). There was a significant survival benefit with altered fractionated radiotherapy, corresponding to an absolute benefit of 3.4% at 5 years (hazard ratio 0.92, 95% CI 0.86-0.97; p=0.003). The benefit was significantly higher with hyperfractionated radiotherapy (8% at 5 years) than with accelerated radiotherapy (2% with accelerated fractionation without total dose reduction and 1.7% with total dose reduction at 5 years, p=0.02). There was a benefit on locoregional control in favour of altered fractionation versus conventional radiotherapy (6.4% at 5 years; p<0.0001), which was particularly efficient in reducing local failure, whereas the benefit on nodal control was less pronounced. The benefit was significantly higher in the youngest patients (hazard ratio 0.78 [0.65-0.94] for under 50 year olds, 0.95 [0.83-1.09] for 51-60 year olds, 0.92 [0.81-1.06] for 61-70 year olds, and 1.08 [0.89-1.30] for over 70 year olds; test for trends p=0.007). Altered fractionated radiotherapy improves survival in patients with head and neck squamous cell carcinoma. Comparison of the different types of altered radiotherapy suggests that hyperfractionation has the greatest benefit.

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Author and article information

Contributors

Anna Merlotti: anna.merlotti@virgilio.it

Daniela Alterio: daniela.alterio@ieo.it

Riccardo Vigna-Taglianti: vigna.r@ospedale.cuneo.it

Alessandro Muraglia: Alessandro.Muraglia@asmn.re.it

Luciana Lastrucci: l.lastrucci@usl8.toscana.it

Roberto Manzo: robertomanzo@inwind.it

Giuseppina Gambaro: giusegambaro@alice.it

Orietta Caspiani: fabriori@libero.it

Francesco Miccichè: francesco.micciche@rm.unicatt.it

Francesco Deodato: fdeodato@rm.unicatt.it

Stefano Pergolizzi: stefano.pergolizzi@unime.it

Pierfrancesco Franco: pierfrancesco.franco@unito.it

Renzo Corvò: renzo.corvo@unige.it

Elvio G Russi: elviorussi@gmail.com

Giuseppe Sanguineti: gsangui1@gmail.com

Journal

Journal ID (nlm-ta): Radiat Oncol

Journal ID (iso-abbrev): Radiat Oncol

Title: Radiation Oncology (London, England)

Publisher: BioMed Central (London )

ISSN (Electronic): 1748-717X

Publication date (Electronic): 29 December 2014

Publication date PMC-release: 29 December 2014

Publication date Collection: 2014

Volume: 9

Issue: 1

Electronic Location Identifier: 264

Affiliations

[ ]Radioterapia AO Ospedale di Circolo-Busto Arsizio (VA), Piazzale Professor G. Solaro, 3, 21052 Busto Arsizio, VA Italy

[ ]Radioterapia IEO-Milano, Milan, Italy

[ ]Radioterapia Az. Ospedaliera S. Croce e Carle-Cuneo, via M. Coppino 26 12100, Cuneo, Italy

[ ]Radioterapia Arcispedale S. Maria Nuova AO-Reggio Emilia, Emilia, Italy

[ ]Radioterapia PO S.Donato-AUSL-Arezzo, Arezzo, Italy

[ ]Radioterapia Azienda Ospedaliera ASL Napoli 1-Napoli, Napoli, Italy

[ ]Radioterapia A.O.U. Maggiore della Carità-Novara, Novara, Italy

[ ]Radioterapia Ospedale Fatebenefratelli, Isola Tiberina-Roma, Roma, Italy

[ ]Radioterapia Policlinico Universitario ‘A.Gemelli’-Roma, Roma, Italy

[ ]Radioterapia Università Cattolica del S. Cuore -Campobasso, Roma, Italy

[ ]Dipartimento SBIMOF Sezione di Scienze Radiologiche, Università di Messina, Piazza Pugliatti Salvatore, 1, 98122 Messina, ME Italy

[ ]Dipartimento di Oncologia, Radioterapia Oncologica, Università di Torino, Turin, Italy

[ ]Oncologia Radioterapica, IRCS S. Martino-IST- Istituto Nazionale per la Ricerca sul Cancro, Università Genova, Genova, Italy

[ ]UOC Radioterapia Istituto Tumori Regina Elena Roma (RM), Roma, Italy

Article

Publisher ID: 264

DOI: 10.1186/s13014-014-0264-9

PMC ID: 4316652

PubMed ID: 25544268

SO-VID: 7f27d5a7-0746-41c7-b21e-9b89134a5c61

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

History

Date received : 19 January 2014

Date accepted : 17 November 2014

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ScienceOpen disciplines: Oncology & Radiotherapy

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ScienceOpen disciplines: Oncology & Radiotherapy

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Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group

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Karger: Oncology

Most cited references 189

Parotid-sparing intensity modulated versus conventional radiotherapy in head and neck cancer (PARSPORT): a phase 3 multicentre randomised controlled trial

Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

Hyperfractionated or accelerated radiotherapy in head and neck cancer: a meta-analysis.

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Cited by 29

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