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.

[New indications of protontherapy for adults intracranial tumours]. / Nouvelles indications de protonthérapie et essais cliniques en cours : tumeurs intracrâniennes.

Considering intracranial tumours, only few indications of protontherapy, such as chordoma, chondrosarcoma or uveal melanoma, are uniformly approved in the world. Other indications, excluding paediatric pathologies, are still debated. The aim of this article is to describe the rationale for the use of protonbeam irradiation for meningioma, pituitary adenoma, craniopharyngioma, paraganglioma, glioma, and schwannoma, and to inform the radiation oncologists if prospective studies or randomized studies are opened for inclusions. This article deals only with indications for adults.

Radiation enteritis: Diagnostic and therapeutic issues.

Abdominal pelvic radiation therapy can induce acute or chronic lesions in the small bowel wall, called radiation enteritis. Treatment of acute radiation enteritis is essentially symptomatic; symptoms regress when radiation is discontinued. Conversely, late toxicity can occur up to 30 years after discontinuation of radiation therapy, posing diagnostic problems. Approximately one out of five patients treated by radiation therapy will present clinical signs of radiation enteritis, including obstruction, malabsorption, malnutrition and/or other complications. Management should be multidisciplinary, centered mainly on correction of malnutrition. Surgery is indicated in case of complications (i.e., abscess, perforation, fistula) and/or resistance to medical treatment; intestinal resection should be preferred over internal bypass. The main risk in case of iterative resections is the short bowel syndrome and the need for definitive nutritional assistance.

Routine feasibility of postoperative chemoradiotherapy in head and neck squamous cell carcinoma at high risk of recurrence.

OBJECTIVE: To assess the feasibility in routine practice of postoperative chemoradiotherapy in head and neck squamous cell carcinoma (HNSCC) at high risk of recurrence. METHOD: A single-center retrospective study recruited all patients receiving postoperative cisplatin chemoradiotherapy for HNSCC at high risk of recurrence. The main endpoints were the rate of complete postoperative chemoradiotherapy and the impact of various clinical factors. Secondary endpoints comprised the impact of completion of therapy on survival and on acute and late toxicity. RESULTS: One hundred and six patients were included. 24.5% showed severe comorbidity. Chemoradiotherapy was complete in 61 patients (57.5%). Radiation therapy was interrupted for >3 days in 16 patients (15.1%). The 3rd concomitant cisplatin course could not be implemented in 34 patients (32.1%). Low pre-treatment glomerular filtration rate was significantly associated (p=0.003) with treatment interruption; >5% weight-loss during treatment showed suggestive association (p=0.026). Completion of treatment was not associated with any significant difference in overall survival (p=0.441) or progression-free survival (p=0.81). 14.9% of patients showed post-treatment kidney failure; there were 10 cases of osteoradionecrosis (9.4%). CONCLUSION: The rate of complete postoperative chemoradiotherapy was comparable to that reported in clinical trials, despite frequent comorbidity and poor nutritional status. Early nutritional support is a key factor for treatment under optimal conditions.

[Proton therapy for head and neck squamous cell carcinomas: From physics to clinic]. / Protonthérapie des carcinomes épidermoïdes des voies aérodigestives supérieures : de la physique à la clinique.

Intensity-modulated radiation therapy (IMRT) is presently the recommended technique for the treatment of locally advanced head and neck carcinomas. Proton therapy would allow to reduce the volume of irradiated normal tissue and, thus, to decrease the risk of late dysphagia, xerostomia, dysgeusia and hypothyroidism. An exhaustive research was performed with the search engine PubMed by focusing on the papers about the physical difficulties that slow down use of proton therapy for head and neck carcinomas. Range uncertainties in proton therapy (±3 %) paradoxically limit the use of the steep dose gradient in distality. Calibration uncertainties can be important in the treatment of head and neck cancer in the presence of materials of uncertain stoichiometric composition (such as with metal implants, dental filling, etc.) and complex heterogeneities. Dental management for example may be different with IMRT or proton therapy. Some uncertainties can be somewhat minimized at the time of optimization. Inter- and intrafractional variations and uncertainties in Hounsfield units/stopping power can be integrated in a robust optimization process. Additional changes in patient's anatomy (tumour shrinkage, changes in skin folds in the beam patch, large weight loss or gain) require rescanning. Dosimetric and small clinical studies comparing photon and proton therapy have well shown the interest of proton therapy for head and neck cancers. Intensity-modulated proton therapy is a promising treatment as it can reduce the substantial toxicity burden of patients with head and neck squamous cell carcinoma compared to IMRT. Robust optimization will allow to perform an optimal treatment and to use proton therapy in current clinical practice.

Impact of locoregional irradiation in patients with upfront metastatic head and neck squamous cell carcinoma.

OBJECTIVE: To evaluate the frequency of use, modalities and potential interest of locoregional irradiation (LRT) in patients with upfront metastatic head and neck squamous cell carcinoma (HNSCC). METHODS: Retrospective multicentric study. Were included all patients presenting an upfront metastatic HNSCC treated by platin-5FU- cetuximab based regimen, from 2008 to 2016. Patients with past history of cervical irradiation or HNSCC within the 5 years before metastasis diagnosis were excluded. RESULTS: 65 patients were included. 25 patients (38%) presented a response or stable disease with chemotherapy. Forty-one patients (63%) underwent a locoregional irradiation: 5 patients before chemotherapy (upfront RT), 13 patients with stable disease or response after chemotherapy (consolidation RT), and 23 patients with progressive disease. Median overall survival (OS) was 11.6 months, median progression free survival was 7.9 months. OS was significantly improved for patients who underwent LRT (median OS 16.1 vs 7.5 months, p < 0.01). Among patients who received LRT, OS trended to be better if LRT was performed as consolidation RT compared to upfront RT (median OS of 22.1 vs 15.5 months, p = 0.11). Among patients with stable disease or response after chemotherapy, there was a non-significant better OS for the 13 patients treated by LRT (median OS 22.1 vs 11.8 months, p = 0.21)). Radical dose was not associated with better locoregional control compared to palliative dose (p = 0.37). CONCLUSION: LRT is frequently performed during management of upfront metastatic HNSCC and associated with better OS. Non-progressive disease after firs-line chemotherapy seems a good way to select patients who would benefit from radical LRT.

Platinum rechallenge in recurrent head and neck squamous cell carcinoma after primary chemoradiation.

OBJECTIVE: To evaluate platinum rechallenge efficacy and tolerance in patients presenting recurrent head and neck squamous cell carcinoma (HNSCC) after platinum-based chemoradiation. MATERIALS AND METHODS: We retrospectively included all patients treated from 2007 to 2016 by platinum-based polychemotherapy for recurrence of HNSCC previously treated by primary or postsurgical platinum-based chemoradiation. The primary end-point was disease control rate (DCR) on platinum rechallenge. RESULTS: Forty-five patients were included. Median disease-free interval (DFI) after chemoradiation was 5.7 months. DCR on platinum rechallenge was 40%. Progression-free survival at recurrence was 3.7 months and overall survival 5.0 months. DCR in patients with recurrence within 6 months of chemoradiotherapy was 47.8%. DFI>4.5 months was associated with better DCR: 28.5% versus 54.8%; P=0.0311. CONCLUSION: Platinum rechallenge provided good DCR in recurrent HNSCC after chemoradiation.

[Re-irradiation of head and neck cancers: Target volumes, technical evolutions and prospects]. / Réirradiation des tumeurs de la tête et du cou : volumes cibles, évolutions techniques et perspectives.

Malignant tumors of the head and neck have a predominantly regional recurrence pattern, with most deaths resulting from this progression. Optimization of re-radiation in recurrence setting is a major objective for these patients. Extensive research has been carried out with the PubMed search engine to find publications dealing with this topic. The first attempts to reirradiate the ORL sphere date back to the 1980s and the first to be performed by intensity modulation conformational radiotherapy (IMRT) date back to the late 1990s. Compared to 3 dimensional conformal radiotherapy, IMRT improves clinical outcomes and reduces toxicity. In IMRT series, associated or not with concomitant chemotherapy, the locoregional control obtained at 2 years was of the order of 45 to 65% and the overall survival of 15 to 60%, depending on predictive factors. Grade 3 acute toxicity occurred on the order of 10 to 30% and late-grade 3 toxicity on the order of 15 to 50%. In a selected population with low volumes tumors, stereotactic re-irradiation at a minimum dose of 35Gy obtained outcome comparable to IMRT. Re-irradiation of head and neck tumors by proton therapy is rare. The toxicity rate appears to be lower than that usually seen after photon therapy. However, we do not have a long follow-up. This technique therefore remains reserved for search protocols and represents a future perspective in these situations.

The Evaluation of Beta-2-Adrenoreceptors' Expression in Normal Peritumoral Tissue in Patients with Colorectal Adenocarcinoma.

INTRODUCTION: The aim of this study is to evaluate the expression of beta-2 adrenergic receptors in the normal peritumoral tissue at the colorectal level, just after the front tumor invasion, in patients with colorectal cancer. METHODS: In this study we analyzed normal peritumoral tissues belonging to 56 patients, who were diagnosed with colorectal adenocarcinoma. These tissues were fixed in paraformaldehyde and paraffinembedded. The immunohistochemical study was done on seriate slides following the hematoxylin and eosin staining, after diagnostic and grading. Correlations were made between beta-2-adrenoreceptors' expression in the normal peritumoral tissue and the clinical and histopathological parameters of the patients with colorectal cancer. RESULTS: There are positive correlations between the expression of beta-2-adrenoreceptors and feminine gender, age group under 50 years, tumor size under 5cm, tumor invasion T3-4 and tumor metastasis in regional lymph nodes N≥2. By analyzing the expression of beta-2-adrenoreceptors in peritumoral tissue depending on tumor grading one can notice that there are positive correlations between beta-2-adrenoreceptors' expression and poorly differentiated colorectal adenocarcinoma. CONCLUSIONS: Positive correlation between this type of receptors in normal glandular epithelium, in the vicinity of tumor invasion front of colorectal neoplasm, and certain clinicopathological features suggests the involvement of tumor microenvironment, which expresses them, in the pathogenesis of this neoplasm.

Local ablative treatments of oligometastases from head and neck carcinomas.

BACKGROUND: Median survival for recurrent/metastatic (unknown poly/oligometastatic status) head and neck cancer patients (HNSCC) is ten months with best systemic treatment. Metastatic ablation shows promising results in selected patients with several tumor types. We aimed to assess the role of surgery and stereotactic ablative body radiotherapy (SABR) with respect to survival in HNSCC. MATERIALS AND METHODS: Published data on metastatic HNSCC treated ablatively were analyzed. RESULTS: Five-year survival rates after pulmonary/liver metastasectomy exceed 20% in selected patients. Two-year survival after lung SABRT of metastasectomy yields 35%. Interesting data on survival and tolerance are reported in other metastatic sites. CONCLUSION: Surgery yields the best level of evidence. However, non-invasive SABR is efficient and well-tolerated in lung/liver, bone and other metastatic locations. Systemic treatment may be given sequentially with ablative treatments, or omitted in well-identified situations. Proper patient selection for local ablative treatment and optimal therapeutic sequence should be assessed in randomized trials.

Exclusive radiotherapy for stage T1-T2N0M0 lanryngeal cancer: retrospective study of 59 patients at CFB and CHU de Caen.

OBJECTIVE: Study of patients with stage T1N0M0 or T2N0M0 glottic cancer treated by exclusive radiotherapy and comparison of the survival and functional results of this series with those of the literature. METHOD: Retrospective study of stage T1N0M0 or T2N0M0 glottic cancers diagnosed between 1st January 2000 and 31st December 2010 and treated by exclusive radiotherapy. Evaluation of survival, recurrence and larynx preservation rates. STUDY CENTRES: CLCC François-Baclesse and CHU de Caen. PATIENTS: Fifty-nine patients (53 men and sixwomen) treated for glottic cancer (57 squamous cell carcinomas, two verrucous carcinomas) comprising 51 T1N0M0 and eight T2N0M0 tumours. Treatment with exclusive radiotherapy (mean dose of 70 Grays limited to the thyroid cartilage for 57 patients, with lymph node irradiation for two patients). RESULTS: In this series, five (9.8%) patients with stage T1N0M0 glottic cancer and three patients (37.5%) with stage T2N0M0 glottic cancer relapsed, corresponding to a global recurrence rate of 13.6%. Three of the eight recurrences involved lymph nodes exclusively (N), two patients relapsed exclusively at the primary tumour site (T) and three patients presented local and lymph node recurrence (T and N). Treatment consisted of salvage total laryngectomy with bilateral cervical lymph node dissection in three cases, bilateral cervical lymph node dissection and sensitized radiotherapy in two cases, exclusive chemotherapy in one case, cervical lymph node dissection and cervical radiotherapy in one case. The last patient with recurrence died prior to salvage therapy. The larynx preservation rate was 94.9%. CONCLUSION: In comparison with the literature, treatment of stage T1-T2N0M0 glottic cancer by exclusive radiotherapy gives very good results, with a larynx preservation rate of 95%.