Systemic therapies for salivary gland carcinoma (excluding adenoid cystic carcinoma): REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the therapeutic indications for systemic medical treatment in the management of salivary gland carcinoma (excluding adenoid cystic carcinoma) according to the clinical situation. MATERIALS AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group who drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Salivary gland carcinoma is rare and there is currently insufficient evidence to indicate chemotherapy at the localized stage. At the metastatic stage, initial management can be based on a phase of monitoring for indolent disease. Some histological subtypes (salivary duct carcinoma and adenocarcinoma) are more aggressive and require systemic treatment from the outset. To guide systemic treatment, it is recommended to perform immunohistochemistry and molecular biology analyses (overexpression of HER2 and androgen receptors, NTRK fusion, next-generation sequencing). CONCLUSION: Salivary gland carcinoma is a rare tumor for which there are currently few effective medical treatments. It is therefore recommended to include patients in clinical trials.

Systemic therapies for salivary gland cancer: Adenoid cystic carcinoma. REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the therapeutic indications for systemic medical treatment in the management of adenoid cystic carcinoma (ACC) according to the clinical situation. MATERIALS AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group, which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: ACCs are rare tumors and there is currently insufficient evidence to indicate chemotherapy at the localized stage. At the metastatic stage, progression is often slow. In case of oligometastatic ACC, local treatment should be discussed. The most often indolent nature of polymetastatic ACC can allow management by active surveillance. Molecular screening is recommended, for abnormalities potentially accessible to targeted therapy. CONCLUSION: ACCs are rare tumors for which there are currently few effective medical treatments. It is therefore recommended to include patients in clinical trials.

Radiotherapy for salivary gland cancer: REFCOR recommendations by the formal consensus method.

OBJECTIVE: To determine the indications for radiotherapy in salivary gland cancer and to specify the modalities and target radiation volumes. MATERIAL AND METHODS: The French Network of Rare Head and Neck Tumors (REFCOR) formed a steering group which drafted a narrative review of the literature published on Medline and proposed recommendations. The level of adherence to the recommendations was then assessed by a rating group, according to the formal consensus method. RESULTS: Postoperatively, radiotherapy to the primary tumor site±to the lymph nodes is indicated if one or more of the following adverse histoprognostic factors are present (risk>10% of locoregional recurrence): T3-T4 category, lymph node invasion, extraglandular invasion, close or positive surgical margins, high tumor grade, perineural invasion, vascular emboli, and/or bone invasion. Intensity-modulated radiation therapy (IMRT) is the gold standard. For unresectable cancers or inoperable patients, carbon ion hadrontherapy may be considered. CONCLUSION: Radiotherapy in salivary gland cancer is indicated in postoperative situations in case of adverse histoprognostic factors and for inoperable tumors.

AFSOS-SFRO-SFH-SFNEP-SFCE-GFRP guidelines on radio-induced nausea and vomiting.

INTRODUCTION: The prevalence of radiation-induced nausea and vomiting varies between 40% and 80%. They have many consequences on treatment and comorbidities. This work thus aimed to define clinical practice guidelines for the management of radiation-induced nausea and vomiting. METHODS: XXXXX, XXXX, XXX, XXXXX, XXXX and XXXX compiled a working group who draft these recommendations. RESULTS: The assessment of the emetogenic risk found two main predictive factors: 1) the irradiated anatomical location, 2) an associated concomitant chemotherapy. In the case of exclusive radiotherapy, primary antiemetic prophylaxis depends on the emetogenic risk (the irradiated anatomical location). In the case of concomitant chemotherapy, the emetogenic risk is generally higher and the primary antiemetic prophylaxis corresponds to that of chemotherapy-induced nausea and vomiting. In cases where symptoms persist, remedial treatments are poorly codified. CONCLUSION: Radiation-induced nausea and vomiting remains underdiagnosed and undertreated, its rapid detection and treatment are essential to reinstate good clinical practice.

Histosurgical mapping of endoscopic endonasal surgery of sinonasal tumours to improve radiotherapy guidance.

PURPOSE: Endoscopic endonasal surgery (EES) is becoming a standard for most malignant sinonasal tumours. Margin analysis after piecemeal resection is complex and optimally relies on accurate histosurgical mapping. Postoperative radiotherapy may be adapted based on margin assessment mapping to reduce the dose to some sinonasal subvolumes. We assessed the use of histosurgical mapping by radiation oncologists (RO). MATERIAL AND METHODS: A French practice survey was performed across 29 ENT expert RO (2 did not answer) regarding integration of information on EES, as well as quality of operative and pathology reportsto refine radiotherapy planning after EES. This was assessed through an electronic questionnaire. RESULTS: EES was ubiquitously performed in France. Operative and pathology reports yielded accurate description of EES samples according to 66.7% of interviewed RO. Accuracy of margin assessment was however insufficient according to more than 40.0% of RO. Additional margins/biopsies of the operative bed were available in 55.2% (16/29) of the centres. In the absence of additional margins, quality of resection after EES was considered as microscopically incomplete in 48.3% or dubious in 48.3% of RO. As performed, histosurgical mapping allowed radiotherapy dose and volumes adaptation according to 26.3% of RO only. CONCLUSIONS: Standardized histosurgical mapping with margin and additional margin analysis could be more systematic. Advantages of accurate EES reporting could be dose painting radiotherapy to further decrease morbidity in sinonasal tumours.

Radiotherapy of salivary gland tumours.

Primary tumours of the salivary glands account for about 5 to 10% of tumours of the head and neck. These tumours represent a multitude of situations and histologies, where surgery is the mainstay of treatment and radiotherapy is frequently needed for malignant tumours (in case of stage T3-T4, nodal involvement, extraparotid invasion, positive or close resection margins, histological high-grade tumour, lymphovascular or perineural invasion, bone involvement postoperatively, or unresectable tumours). The diagnosis relies on anatomic and functional MRI and ultrasound-guided fine-needle aspiration for the diagnostic of benign or malignant tumors. In addition to patient characteristics, the determination of primary and nodal target volumes depends on tumor extensions and stage, histology and grade. Therefore, radiotherapy of salivary gland tumors requires a certain degree of personalization, which has been codified in the recommendations of the French multidisciplinary network of expertise for rare ENT cancers (Refcor) and may justify a specialised multidisciplinary discussion. Although radiotherapy is usually recommended for malignant tumours only, recurrent pleomorphic adenomas may sometimes require radiotherapy based on multidisciplinary discussion. An update of indications and recommendations for radiotherapy for salivary gland tumours in terms of techniques, doses, target volumes and dose constraints to organs at risk of the French society for radiotherapy and oncology (SFRO) was reported in this article.

[State of art of photobiomodulation in the management of radiotherapy adverse events: Indications and level of evidence]. / État de l'art de la photobiomodulation dans la prise en charge des effets secondaires de la radiothérapie : indications et niveaux de preuve.

PURPOSE: To evaluate the current and potential indications of photobiomodulation (PBM) and their level of evidence in the prevention or management of radiation therapy-related side effects. MATERIALS AND METHODS: The Embase, Medline/PubMed, Cochrane, EBSCO, Scopus, and LILACS databases were systematically reviewed to include and analyze publications of clinical studies that have assessed PBM in the prevention or management of radiotherapy-related side effects. The keywords used were "photobiomodulation"; "low level laser therapy"; "acute oral mucositis"; "acute dysphagia"; "acute radiation dermatitis"; "lymphedema"; "xerostomia"; "hyposalivation"; "trismus"; "bone necrosis"; "osteoradionecrosis"; and "radiation induced fibrosis". Prospective studies were included, whereas retrospective cohorts and non-original articles were excluded from the analysis. RESULTS: PBM in the red or infrared spectrum has demonstrated efficacy in randomized controlled trials in the prevention and management of radiotherapy-related side effects, especially acute oral mucositis, acute radiation dermatitis, and upper extremity lymphedema. The level of evidence associated with PBM was heterogeneous, but overall was still moderate. The main shortcomings were the diversity and lack of detail in treatment protocols, which could have compromised efficiency and reproducibility of PBM results. CONCLUSION: The published data suggest that PBM may be considered as a full-fledged supportive care for patients treated with radiotherapy, or at least in the setting of a therapeutic clinical trial. However, until strong evidence has been published on its long-term safety, the use of PBM should be considered with caution, specifically when applied near areas with proven or potential tumors. The patient should be informed of the theoretical benefits and risks of PBM in order to obtain his informed consent before treatment.

Oral Mucosal Injury Caused by Targeted Cancer Therapies.

Targeted cancer therapies have fundamentally transformed the treatment of many types of cancers over the past decade, including breast, colorectal, lung, and pancreatic cancers, as well as lymphoma, leukemia, and multiple myeloma. The unique mechanisms of action of these agents have resulted in many patients experiencing enhanced tumor response together with a reduced adverse event profile as well. Toxicities do continue to occur, however, and in selected cases can be clinically challenging to manage. Of particular importance in the context of this monograph is that the pathobiology for oral mucosal lesions caused by targeted cancer therapies has only been preliminarily investigated. There is distinct need for novel basic, translational, and clinical research strategies to enhance design of preventive and therapeutic approaches for patients at risk for development of these lesions. The research modeling can be conceptually enhanced by extrapolating "lessons learned" from selected oral mucosal conditions in patients without cancer as well. This approach may permit determination of the extent to which pathobiology and clinical management are either similar to or uniquely distinct from oral mucosal lesions caused by targeted cancer therapies. Modeling associated with oral mucosal disease in non-oncology patients is thus presented in this context as well. This article addresses this emerging paradigm, with emphasis on current mechanistic modeling and clinical treatment. This approach is in turn designed to foster delineation of new research strategies, with the goal of enhancing cancer patient treatment in the future.

[Implementation of the tracer patient audit in a private radiation therapy centre]. / Mise en place de l'audit patient traceur au sein d'un centre privé de radiothérapie.

The "tracer patient" audit is an evaluation method introduced by the French health authority in the V2014 certification. This is not mandatory in private radiotherapy centres. In our continuous quality improvement approach and in order to improve the management of patient care, the management of our radiation therapy centre has decided to use this method to evaluate our medical practice and to engage healthcare professionals at the core of this approach.

Candidate apoptotic and DNA repair gene approach confirms involvement of ERCC1, ERCC5, TP53 and MDM2 in radiation-induced toxicity in head and neck cancer.

INTRODUCTION: Single nucleotide polymorphisms (SNPs) of DNA repair and apoptosis genes have been associated with outcome in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT). Our goal was to conduct a candidate gene study in HNSCC patients receiving RT or chemoRT. METHODS: 122 non-resectable HNSCC patients undergoing RT (N=38) or chemoRT (N=84) between 1992 and 2006 were retrospectively analyzed. ERCC1 Lys259Thr (rs735482), ERCC2 Lys751Gln (rs13181), ERCC5 His46His C>T (rs1047768), XRCC1 Arg399Gln (rs25487), TP53 Arg72Pro (rs1042522) and MDM2 309T>G (rs2279744) were analyzed on tumor DNA. SNP profile was considered to assess RT-related toxicity. RESULTS: All 120 evaluable patients experienced RT-related toxicity at any time. Among them, 83% had G3-4 acute side-effects during RT, mainly dysphagia, mucositis, epithelitis and/or xerostomia (DMEX). 28/105 patients (27%) had early G3-4 toxicity up to 3months after the end of RT. 29/96 patients (30%) had G3-4 late toxicity thereafter. The presence of G allele of MDM2 or Thr allele of ERCC1 was associated with a significantly higher risk of acute and/or early DMEX toxicity. The MDM2 309GG genotype was linked to a higher risk of acute G3-4 dermatitis. The ERCC5 TT genotype was associated with more frequent G3-4 late cervical skin fibrosis or xerostomia. Pro allele of TP53 72 was associated with a higher risk of G3-4 osteoradionecrosis. CONCLUSION: Relevant SNPs in DNA repair (ERCC1 and ERCC5) and apoptosis (MDM2 and TP53) genes might influence the severity of radiation-related side-effects in HNSCC patients. Prospective clinical SNP-based validation studies are needed on these bases.

[Intensity-modulated radiotherapy for head and neck cancer. Dose constraint for salivary gland and mandible]. / Radiothérapie conformationnelle avec modulation d'intensité des cancers des voies aérodigestives supérieures. Dose de tolérance des tissus sains : glandes salivaires et mandibule.

Intensity-modulated radiation therapy (IMRT) is the gold standard for head and neck irradiation. It allows better protection to the organs at risk such as salivary glands and mandible, and can reduce the frequency of xerostomia, trismus and osteoradionecrosis. At the time of treatment planning, the mean dose to a single parotid gland should be kept below 26Gy, the mean dose to a single submandibular gland below 39Gy, the mean dose to the mandible below 60 to 65Gy and the D2% to a single temporomandibular joint below 65Gy. These dose constraints could be further improved with data extracted from cohorts of patients receiving IMRT exclusively. The dose administered to the target volumes should not be lessened to spare the salivary glands or mandible.

Guidelines (short version) of the French Otorhinolaryngology - Head and Neck Surgery Society (SFORL) on patient pathway organization in ENT: The therapeutic decision-making process.

OBJECTIVES: The authors present the guidelines of the French Otorhinolaryngology - Head and Neck Surgery Society (SFORL) for patient pathway organization in head and neck cancer, and in particular for multidisciplinary team meetings. The present article concerns the therapeutic decision-making process. METHODS: A multidisciplinary work group was entrusted with a review of the scientific literature on the above topic. Guidelines were drawn up, based on the articles retrieved and the group members' individual experience. They were then read over by an editorial group independent of the work group. The final version was established in a coordination meeting. The guidelines were graded as A, B, C or expert opinion, by decreasing level of evidence. RESULTS: It is recommended that: an organ specialist should contribute to all multidisciplinary meetings on head and neck cancer; all members of the multidisciplinary meeting should have specific knowledge in head and neck cancer; any referring physician who does not follow the multidisciplinary meeting's advice should justify that decision; there should be sufficient time to prepare, discuss and sum up the cases dealt with in the multidisciplinary team meeting.

[Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy]. / Place de l'arcthérapie modulée et de la chimiothérapie concomitante dans la prise en charge des cancers du canal anal localement évolués.

The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed.

[Radiation therapy for pleomorphic adenoma of the parotid]. / Adénomes pléomorphes parotidiens récidivants : place de la radiothérapie.

Parotid pleomorphic adenoma is the most frequent tumor of salivary glands. The prognosis depends on the recurrences because they could lead to iatrogenic events (facial paralysis). Moreover the risk of malignant transformation increases with the number of local relapses. This article aims at reviewing histological and radiological criteria and the surgical techniques. To improve local control, adjuvant irradiation (in first intention or after recurrence) may be useful but is still controversial for benign tumors in young patients with a risk of radio-induced cancer. We listed studies in which adjuvant radiotherapy was used so as to define its place in the treatment strategy. Prognostic factors were found by some authors. Other studies have to be done before strong evidence-based recommendations are issued.

[Target volumes in cervical lympadenopathies of unknown primary: toward a selective customized approach? On behalf of REFCOR]. / Volumes cibles en radiothérapie des adénopathies cervicales de primitif inconnu : état des lieux et pistes vers une approche sélective raisonnée sous l'égide du Refcor (Réseau d'expertise français des cancers ORL rares).

The treatment of carcinomas of unknown primary revealed by cervical lymphadenopathy is based on neck dissection and nodal and pan-mucosal irradiation to control the neck and avoid the emergence of a metachronous primary. The aim of this review was to assess diagnostic and therapeutic approaches and criteria that may be used for a customized selective approach to avoid severe toxicities of pan-mucosal irradiation. A literature search was performed with the following keywords: cervical lymphadenopathy, unknown primary, upper aerodigestive tract, cancer, radiotherapy, squamous cell carcinoma, variants. The diagnostic workup includes a head and neck scanner or MRI, ((18)F)-FDG PET CT, a panendoscopy and tonsillectomy. Squamous cell carcinoma represents over two thirds of cases. The number of metastatic cervical nodes, nodal level, and histological variant (associated with HPV/EBV status) may determine the primary site origin and might be weighted for the determination of radiation target volumes on a multidisciplinary basis. A selective customized approach is relevant to decrease radiation toxicity only if neck and mucosal control is not impaired. Although no recommendation can yet be made in the absence of sufficient level of evidence, the relevance of systematic pan-mucosal irradiation appears questionable in a number of clinical situations. Accordingly, a customized selective redefinition of target volumes may be discussed and be prospectively evaluated in relation to the therapeutic index obtained.

[Advances in head and neck cancers on behalf of the French Intergroup ORL and GORTEC]. / Évolution des concepts dans les cancers des voies aérodigestives supérieures, sous l'égide de l'Intergroupe ORL (GORTEC, GETTEC, GERCOR).

Head and neck cancers are the fifth among the most common cancers in France. Two thirds of cases occur at an advanced stage. For advanced disease, progression-free survival, despite undeniable progress, remains below 50% at three years. The last 20 years have been marked by the necessity to identify situations where less intense surgery and/or radiotherapy and/or chemotherapy is possible without jeopardizing the prognosis, and situations where a therapeutic intensification is necessary and results in a gain in survival while better preserving function with less toxicity. French cooperative groups gathering radiation oncologists (GORTEC), surgeons (GETTEC) and medical oncologists or physicians involved in the management of systemic treatments in head and neck cancers (GERCOR) are now belonging to the INCa-labelled Intergroup ORL to deal with the challenges of head and neck cancers.

Algorithm for dermocosmetic use in the management of cutaneous side-effects associated with targeted therapy in oncology.

Currently, numerous patients who receive targeted chemotherapy for cancer suffer from disabling skin reactions due to cutaneous toxicity, which is a significant problem for an increasing number of patients and their treating physicians. In addition, using inappropriate personal hygiene products often worsens these otherwise manageable side-effects. Cosmetic products for personal hygiene and lesion camouflage are part of a patients' well-being and an increasing number of physicians feel that they do not have adequate information to provide effective advice on concomitant cosmetic therapy. Although ample information is available in the literature on pharmaceutical treatment for cutaneous side-effects of chemotherapy, little is available for the concomitant use of dermatological skin-care products with medical treatments. The objective of this consensus study is to provide an algorithm for the appropriate use of dermatological cosmetics in the management of cutaneous toxicities associated with targeted chemotherapy such as epidermal growth factor receptor inhibitors and other monoclonal antibodies. These guidelines were developed by a French and German expert group of dermatologists and an oncologist for oncologists and primary care physicians who manage oncology patients. The information in this report is based on published data and the expert group's opinion. Due to the current lack of clinical evidence, only a review of published recommendations including suggestions for concomitant cosmetic use was conducted.

Chemoradiation in anaplastic thyroid carcinomas.

BACKGROUND: ATC represents 1-2% of all thyroid carcinomas. Median survival is poor (3-10 months). Our goal is to update recommendations for RT in the context of new irradiation techniques. MATERIALS AND METHODS: A search of the French and English literature was performed with terms: thyroid carcinoma, anaplastic, chemoradiation, radiation therapy and surgery. Level-based evidence remains limited in the absence of prospective studies and the small size of retrospective series of this rare tumor. RESULTS: Surgery when possible should be as complete as possible but without mutilation given the 8-month median survival of ATC. It should be followed by systematic chemoradiation in ATC. Initiation of treatment is an emergency given fast tumor doubling time. The most promising results of chemoradiation to date have been shown in series of radiation therapy (+/- acceleration) combined with doxorubicin +/- taxanes or cisplatin. Adjuvant chemotherapy (doxorubicin, cisplatine and/or taxane-based) may also be recommended given the metastatic potential of ATC and warrants further investigations. Data on neoadjuvant chemotherapy are missing. Intensity modulated radiation therapy offers clear dosimetric advantages and has the potential to improve tumor and nodal (posterior neck, mediastinum) coverage, i.e., locoregional control while optimally sparing the spinal cord, larynx, parotids, trachea and esophagus. PET-CT and MRI may be used for RT planning. CONCLUSION: Chemoradiation with debulking surgery whenever possible is the mainstay of treatment of anaplastic thyroid carcinomas (ATC). EBRT using IMRT has the potential to improve local control. Taxane-doxorubicin concomitant chemoradiotherapy is worth further investigation.