Merlotti et al. Radiation Oncology (2014) 9:264 DOI 10.1186/s13014-014-0264-9 REVIEW Open Access Technical guidelines for head and neck cancer IMRT on behalf of the Italian association of radiation oncology - head and neck working group Anna Merlotti1†, Daniela Alterio2†, Riccardo Vigna-Taglianti3†, Alessandro Muraglia4†, Luciana Lastrucci5†, Roberto Manzo6†, Giuseppina Gambaro7†, Orietta Caspiani8†, Francesco Miccichè9†, Francesco Deodato10†, Stefano Pergolizzi11†, Pierfrancesco Franco12†, Renzo Corvò13†, Elvio G Russi3*† and Giuseppe Sanguineti14† 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. Introduction Material and methods Performing intensity-modulated radiotherapy (IMRT) The first participants (AM, DA, AM, LL, RM, GG, OC, in head and neck cancer patients (HNCPs) requires FM, FD and RC) were chosen on a voluntary basis training [1] and experience. For example, in the 02–02 among the HNCWG members. The group was coordi- Trans Tasman Radiation Oncology Group (TROG) nated by an expert head and neck radiation oncologist trial, comparing cisplatin (P) and radiotherapy (RT) (RC). Each member was in charge of a specific topic. with or without tirapazamine, a major quality defect of At the end of the first draft (February 2012) the whole the irradiation approach in terms of dose and target document was reviewed by all the HNCWG members volume selection and delineation was found in 12% of in order to discuss critical issues and to homogenize patients and was associated with a 24% lower loco- the manuscript structure. The revised draft was again regional control rate at 2 years [2]. Hence, in 2011, the reviewed by 5 radiation oncologists with particular Head and Neck Cancer Working Group (HNCWG) of expertise in head and neck IMRT (RVT, PF, SP, ER the Italian Association of Radiation Oncology (AIRO) and GS). organized a study group to outline clinical practice recommendations regarding techniques, treatment vol- umes and doses to be employed during head and neck General aspects IMRT. The main purpose was to standardize technical Treatment strategy approaches of professionals participating into AIRO head RT is one of the mainstay treatment options for head and neck cancer trials. and neck cancers (HNCs), along with chemotherapy (ChT) and surgery (S). In general, RT ± ChT is the pre- ferred approach for head and neck squamous cell carcin- * Correspondence: [email protected] †Equal contributors omas (HN-SCC) whenever organ preservation is desired 3Radioterapia Az. Ospedaliera S. Croce e Carle-Cuneo, via M. Coppino 26 or the tumor is unresectable at presentation (cT4b) or 12100, Cuneo, Italy the patient is considered not amenable to surgery. For Full list of author information is available at the end of the article early T-stage lesions (cT1 and selected cT2) without © 2014 Merlotti et al.; licensee BioMed Central. 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. Merlotti et al. Radiation Oncology (2014) 9:264 Page 2 of 32 lymph nodes involvement (cN0), treatment should be conformal RT (3DCRT) and this in turn allows for better monomodal (RT vs S), while for locally advanced disease sparing of normal structures (i.e. parotid glands). This (cT3-cT4 or any T,cN+), treatment is usually multimodal potentially translates into fewer late side effects (xeros- (S followed by RT ± ChT vs RT and concomitant ChT ± S). tomia) and improved quality of life [14]. With IMRT, Concomitant ChT (usually platinum-based) has been the physician identifies the target volumes(s) and the shown to increase overall survival (OS) in stage III organs at risk (OARs) appropriate for a given clinical and IV disease over RT alone [3]. Recently published condition. The dose to the target is usually proportional long-term results of the RTOG 91–11 trial in larynx can- to the estimated tumour burden (Table 1 and Figure 1). cer failed to show such an advantage over sequential ChT- It should be noted that the maximum prescribed dose RT because of an increased number of non-cancer-related has empirically evolved as the highest tolerated dose tak- deaths in the concomitant arm, suggesting a higher long- ing into account the surrounding normal structures. A term toxicity rate for ChT-RT [4]. Induction and adjuvant ‘definitive’ treatment typically includes 2–3 dose levels ChT are less effective than concomitant ChT [3,5]. How- within the same patient. Using IMRT a different dose to ever, within an organ preservation strategy, induction ChT different targets can be delivered with sequential plans may become an option to select responders who might (as for 3DCRT) or with a simultaneous integrated boost potentially benefit from an organ preservation approach, (SIB). It has been shown that the latter approach pro- driving eventual further treatments (S vs RT) on the basis vides better dose conformity compared to several con- of response to neoadjuvant ChT [6,7]. Recent published secutive plans [15]. When a single plan is prescribed, trials found no benefit from the addition of Taxotere(T)- CTV1 receives both a higher total dose and a higher Platinum (P)-5Fluorouracil(F) induction ChT to concomi- dose/fraction (d./f.) compared to the other CTVs. This tant ChT/RT or cetuximab-RT compared to concomitant results in an even higher biologically equivalent dose ChT/RT or RT alone [8-10]. Another alternative to con- (BED) compared to other CTVs. However, since all dose comitant ChT is cetuximab, an epidermal growth factor re- levels are delivered throughout the same number of frac- ceptor inhibitor, which, combined to RT, has been shown tions, targets must receive different fractionations. to provide a better OS than RT alone in HN-SCC [11]. Two solutions have been proposed [16] (see Table 1). However, Erbitux has never been tested against the The first approach is to maintain conventionally frac- standard treatment (concomitant platinum-based ChT- tionated doses to the highest dose CTV (1.8-2 Gy per RT) and consequently its role is somewhat unclear. fraction) (Table 1) whereas the elective targets receive a Moreover, when Erbitux was added to concomitant lower d./f. (1.6-1.8 Gy). The choice of the latter is made ChT-RT, no additional benefit was found [12]. After taking into consideration the normalized total dose in concomitant ChT-RT, S is usually reserved for eventual 2 Gy fractions (NTD). The second strategy is to deliver locoregional disease persistence. Regarding neck man- a slightly hypofractionated dose to the GTV and stand- agement, most Institutions nowadays use FDG-PET/CT ard fraction doses to the CTVs [17]. Each strategy has at 10–12 weeks to select patients at risk of for residual pros and cons and no universally accepted schedule has nodal disease [13]. The decision to add adjuvant treat- been developed. The former solution may lead to the ments after upfront surgery is made once the pathology use of a very low d./f. according to current standards; a report is available. RT is usually added for high risk fea- daily d./f. below 1.6 Gy should be avoided. Notably, in tures including positive resection margins (PRMs), one study, 58.1 Gy in 35 fractions were able to control advanced T stage (selected pT3 and all pT4), perineu- the microscopic low-risk disease [18]. The latter ap- ral invasion, lymph-vascular invasion, any nodal stage proach has the disadvantage of using a higher d./f. (up higher than pN1, and extra-capsular lymph-nodal ex- to 2.5 Gy) than the standard fractionation for the GTV tension (ECE); ChT is added for PRM and ECE. There- potentially exposing normal tissues embedded within the fore, treatment is usually multidisciplinary and any high dose CTV to the risk of increased late toxicity. decision should be discussed within the tumor board Moreover, this results in a higher than standard weekly involving all specialties. Aspects such as nutrition, oral total dose to normal tissues (i.e. mucosa) within the high care and restoration/preservation of swallowing and dose region. According to some authors [19], 66 Gy/ phonatory function (speech therapy) are also important 30 f. (2.2 Gy) should not be used in the context of con- and should be considered whenever feasible. comitant CT. On the other hand, a d./f. up to 2.12 Gy is used in the context of concomitant CT (P, 100 mg/m2 x IMRT (Intensity-Modulated Radiation Therapy) 3 cycles) for nasopharyngeal cancer [20]. Recently some Though few Institutions pioneered IMRT for HN-SCC authors have reported initial experience in advanced during mid-90s, this technique has become widespread HNC with a d./f. up to 2.25 Gy in 30 fractions concomi- during the last decade. The aim of IMRT is to achieve tantly to CT.