[Ten years of advances in head and neck surgery, how does this influence postoperative radiotherapy?] / Dix ans de progrès en chirurgie des tumeurs de la tête et du cou, quel impact sur la radiothérapie postopératoire ?

Minimal invasive surgery and reconstructive surgery tend to become the standard in France in the management of head and neck tumors. The use of endoscopic approaches (through endoscopic endonasal/transoral approaches±robot-assisted) instead of open surgery and the use of reconstructive surgery using autologous (flaps) or heterologous materials aim to reduce surgical morbidity by making-up for the loss of substance to restore the function. The impact of these substantial changes in surgical techniques has not been assessed with respect to postoperative radiotherapy practice. Endoscopic endonasal approaches result, however, in piecemeal resection, which, along the analysis of resection margins (a key prognostic factor), make the interpretation of the quality of resection more complex for radiation oncologists. The definition of tumour sub-volumes to be irradiated and doses to these sub-volumes then requires accurate histosurgical mapping and close multidisciplinary consultation between surgeons, pathologists, radiologists and radiation oncologists. Similarly, the increasing use of various types of flaps (of soft tissue or bone flaps), adapted to the patient and tumor anatomy, is associated with substantial modifications to the operating bed. The delineation of tumour volumes in postoperative radiotherapy is made more complex. Tremendous multidisciplinary efforts should now be initiated to fully take advantage of surgical advances and to further optimize the therapeutic index by making radiotherapy also less toxic, i.e. "mini-morbid".

Proton therapy for head and neck squamous cell carcinomas: A review of the physical and clinical challenges.

The quality of radiation therapy has been shown to significantly influence the outcomes for head and neck squamous cell carcinoma (HNSCC) patients. The results of dosimetric studies suggest that intensity-modulated proton therapy (IMPT) could be of added value for HNSCC by being more effective than intensity-modulated (photon) radiation therapy (IMRT) for reducing side effects of radiation therapy. However, the physical properties of protons make IMPT more sensitive than photons to planning uncertainties. This could potentially have a negative effect on the quality of IMPT planning and delivery. For this review, the three French proton therapy centers collaborated to evaluate the differences between IMRT and IMPT. The review explored the effects of these uncertainties and their management for developing a robust and optimized IMPT treatment delivery plan to achieve clinical outcomes that are superior to those for IMRT. We also provide practical suggestions for the management of HNSCC carcinoma with IMPT. Because metallic dental implants can increase range uncertainties (3-10%), patient preparation for IMPT may require more systematic removal of in-field alien material than is done for IMRT. Multi-energy CT may be an alternative to calculate more accurately the dose distribution. The practical aspects that we describe are essential to guarantee optimal quality in radiation therapy in both model-based and randomized clinical trials.

Implantation of tissue expander prior to irradiation in the era of intensity modulated radiotherapy: impact on the management of patients with pelvic digestive cancers.

PURPOSE: Before the introduction of intensity-modulated radiation therapy (IMRT), few teams used to implant a pelvic tissue expander to keep the bowel away from the radiation field, so as to reduce the risk of acute and late enteritis. However, this unexpected surgery could impact patient's overall treatment and may be no more necessary in the era of modern radiotherapy. MATERIAL AND METHODS: This is a retrospective cross-sectional study including 13 patients who underwent tissue expander implantation before radiotherapy or chemoradiotherapy for rectal or anal carcinoma between November 2008 and March 2019. First, we aim to show that IMRT could sometimes be insufficient to respect dosimetric constraints, and then we aim to report the impact of tissue expander implantation on the global strategy of care of patients with anal and rectal cancers. RESULTS: Seventy-seven percent of the included patients were treated for anal neoplasms, while the remaining 23% had locally advanced rectal cancer. The median follow-up since implantation of the expander was 51 months [3.7-115]. Three patients recurred. One patient developed grade III toxicity related to the implantation of a tissue expander. The delay between diagnosis and the start of irradiation was significantly prolonged (median of 3 months), requiring unusual induction chemotherapy. CONCLUSION: Implantation of tissue expander prior to chemoradiotherapy should be considered, even in the era of IMRT, when irradiated peritoneal cavity volume (V15Gy-V45Gy) far exceeds usual dose constraints. However, it impacts the global strategy of care by delaying the start of irradiation, by introducing induction chemotherapy, and rarely by causing post-operative complications.

[Systemic treatments of metastatic or locally recurrent adenoid cystic carcinoma of the head and neck, a systematic review]. / Traitements systémiques du carcinome adénoïde kystique de la sphère ORL localement avancé ou métastatique, une revue systématique.

INTRODUCTION: Adenoid Cystic Carcinoma is a rare tumor of the head and neck sphere. The purpose of this review is a state of the art of systemic treatments (chemotherapies, targeted therapies, immunotherapies) for locally recurrent or metastatic disease. MATERIAL AND METHODS: Our inclusion criteria included head and neck adult patient, metastatic or locally advanced, treated by a systemic therapy, and with at least 10 or more patients. RESULTS: Forty articles have been selected in this review. The objective response rate under chemotherapy was predominantly<10% (0-70%) with objective responses in monotherapy with cisplatin, mitoxantrone, vinorelbine and eribuline, and with cisplatin-vinorelbine combination. EGFR inhibitors provided 40% objective responses only in combination. Inhibitors of VEGF and histone deacetylase have allowed disease stabilization in progressive patients, with about 10% of objective response. Inhibitors of c-KIT monotherapy yield objective response rates of<5%. Direct inhibitors of the PI3K/AKT/mTOR pathway display 0% objective response rate. CONCLUSION: The best objective response rates were obtained with cisplatin-vinorelbine combination. Many targetable molecular abnormalities have been identified and studies have shown prolonged stabilization with EGFR, VEGF and HDAC inhibitors. Multi-disciplinary collaborative consultation (MCC) meetings such as French network of experts in rare head and neck tumors (REFCOR) or Molecular MCC should be proposed and may allow referral to centers proposing specific therapeutic trials.

Approach to oligometastatic disease in head and neck cancer, on behalf of the GORTEC.

Median survival for recurrent/metastatic head and neck squamous cell cancer (HNSCC) patients is about 10 months after first-line best systemic treatment. We aimed to assess current approaches of oligometastatic HNSCC patients by the analysis of current concept and published data (1995-2017) in this population. Five-year survival rates are over 20% in selected patients who undergo metastasis-directed therapy by either surgery or stereotactic irradiation. Human papillomavirus(+) HNSCC patients have more disseminated metastases but respond more favorably and also benefit from ablative treatments. Treatments of oligometastases are expanding rapidly. Unmet needs include revised imaging follow-up strategies to detect metastases earlier, identification of predictive noninvasive biomarkers for treatment guidance, assessment and corrections of biases in current studies and randomized clinical trials.

Retrospective evaluation of concomitant cetuximab and radiotherapy tolerance for locoregional advanced head and neck squamous cell carcinoma treatment in patients unfit for platinum-based chemotherapy.

Radiotherapy associated with cetuximab (Cet-RT) is an alternative treatment to platinum-based chemoradiotherapy in locally advanced head and neck carcinoma (LAHNC). Reviews suggest that the use of cetuximab is associated with poorer tolerance in patients unfit for chemotherapy than in pivotal trial. We retrospectively studied patients first treated by Cet-RT for LAHNC presenting contraindications to chemoradiotherapy. Objectives were treated population description, acute tolerance, progression-free survival (PFS), overall survival (OS), and 3-month clinical response. Eighty-eight patients were included. Treatment was completed without delay for 43 patients. Grade 3-4 acute toxicity was described in 44.3%: mucositis (n = 20), radiodermatitis (n = 25) folliculitis (n = 10), and anaphylaxis (n = 6). Fourteen patients died during treatment. Median PFS and OS were 6.3 and 18.7 months, respectively. We confirm that Cet-RT tolerance in unfit patients is poorer than that in trials. Survival data illustrate patients' frailty and suggest that balanced use of Cet-RT is required in this population.

Utility of serum anti-cetuximab immunoglobulin E levels to identify patients at a high risk of severe hypersensitivity reaction to cetuximab.

AIM: Cetuximab is an anti-epidermal growth factor receptor antibody used for the treatment of metastatic colorectal cancer and head and neck cancer. Hypersensitivity reactions (HSRs) are associated with cetuximab use. The aim of the study was to evaluate the utility of anti-cetuximab immunoglobulin E (IgE) detection in order to identify patients at risk of HSR to cetuximab. METHODS: We included patients ready to receive a first cetuximab infusion in a prospective cohort carried out at nine French centres. Pretreatment anti-cetuximab IgE levels were measured. We compared the proportion of severe HSRs in the low anti-cetuximab IgE levels (≤29 IgE arbitrary units) subgroup with that in a historical cohort of 213 patients extracted from a previous study. RESULTS: Of the 301 assessable patients (mean age: 60.9 ± 9.3 years, head-and-neck cancer: 77%), 66 patients (22%) had high anti-cetuximab IgE levels, and 247 patients received cetuximab (including 38 with high anti-cetuximab levels). Severe HSRs occurred in eight patients (five grade 3 and three grade 4). The proportion of severe HSRs was lower in the low anti-cetuximab IgE levels subgroup vs. the historical cohort (3/209 [1.4%] vs. 11/213 [5.2%], odds ratio, 0.27, 95% confidence interval, 0.07-0.97), and higher in high vs. low anti-cetuximab IgE levels subgroup (5/38 [13.2%] vs. 3/209 [1.4%]; odds ratio, 10.4, 95% confidence interval, 2.4-45.6). Patients with severe HSRs had higher anti-cetuximab IgE levels than patients without reaction (median, 45 vs. 2 IgE arbitrary units, P = 0.006). CONCLUSIONS: Detection of pretreatment anti-cetuximab IgE is feasible and helpful to identify patients at risk of severe cetuximab-induced HSRs.

[Oropharyngeal cancer]. / Cancer de l'oropharynx.

Oropharyngeal carcinomas, contrary to other head and neck carcinomas are of increasing frequency, mostly due to a frequent association with human papillomavirus infection. Pluridisciplinary management is necessary. New techniques as transoral surgery or intensity-modulated radiation therapy have the potential to reduce toxicities and morbidity while offering equivalent local control rates. Early stages may be treated with single modality treatment (surgery or radiotherapy) with five-year overall survival rate exceeding 80%. Advanced stages need therapeutic associations and five-years survival rates are inferior to 40%.

Elements of renal injury in patients with varicose ulcer. Preliminary study.

The kidney may be affected in the processes of microbial, viral, parasitic infections. Knowledge of renal disease during chronic infection, with a different location than the throat, is of particular importance for the practicing physician for the detection and prevention of impaired renal function. Chronic kidney disease recovered in the early stages can prevent the progression of renal function decline. We studied a total of 85 patients with varicose ulcers with a mean age of 66.78 +/- 12.09 years, hospitalized in the Clinic of Dermatology and a control group consisting of 110 apparently healthy individuals. Urinary abnormalities have been detected in 26 (30%) of patients studied. GFR < 60 ml/min have been detected in 14 (17%) of patients studied. CRF stage II have been detected in 36 (42%) of patients studied. We detected recurrent varicose ulcer in 2 (2%) of patients studied. In two (2%) of patients during hospitalization we found a decrease in GFR by 15 and 12 ml/min, accompanied by an increase in serum creatinine from 0.7 mg % to 1 mg % in one patient and in another patient from 1.5 mg % to 2 mg %. Urinary abnormalities detected in patients with both acute and recurrent erysipelas warn about renal impairment and the need for monitoring of the renal patients with varicose ulcers.

Postoperative radiotherapy in head and neck mucosal melanoma: a GETTEC study.

OBJECTIVE: to report patterns of failure according to treatment modality, with an emphasis on the role of postoperative radiotherapy in patients with localized head and neck mucosal melanoma (HNMM) treated during a 28-year period in a multi-institutional setting. DESIGN: retrospective review. SETTING: french medical institutions. PATIENTS: a total of 160 patients with nonmetastatic HNMM treated from 1980 through 2008. INTERVENTIONS: treatment modality consisted of surgery alone (hereinafter, S group) (n = 82 patients) or with postoperative radiotherapy (hereinafter, SRT group) (n = 78). Patients and tumor characteristics were similar in the 2 groups. There was a nonsignificant trend (P = .11) for more locally advanced tumor stage (38.9%) in the SRT group compared with the S group (24.5%). RESULTS: patients in the S group had an increased probability of locoregional recurrence as a first event (55.6%) compared with those in the SRT group (29.9%; P < .01). After adjusting for tumor stage (T1/T2 vs T3/T4), the subdistribution hazard ratio of locoregional relapse was 0.31, (95% confidence interval [CI], 0.15-0.61; P < .01).The rate of distant metastasis as a first event was significantly higher in the SRT group (40.6%) compared with the S group (19.9%; P = .01). Regardless of their treatment, patients who had a locoregional relapse during follow-up had an increased risk of subsequent distant metastasis (hazard ratio, 3.07; 95% CI, 1.65-5.67) and death (hazard ratio, 3.01; 95% CI, 1.91-4.78). CONCLUSIONS: this large retrospective study suggests that postoperative radiotherapy improves the locoregional control of HNMM. The higher rate of distant metastasis was due to more advanced disease in the SRT group.

Elements of renal injury in patients with erysipelas.

Erysipelas is an infectious disease caused by group A beta hemolytical streptococci which may produce renal lesions, most frequently glomerular disease. Renal injury although known is less studied in practice. Rarely bioptical exams have been performed, thus the problem of the relationship erysipelas glomerular disease is practically not solved. The aim of this study was a cross-sectional analysis of renal involvement produced by erysipelas in two departments where patients with erysipelas are diagnosed and treated: Dermatology and Infectious Diseases. We investigated 166 patients (86M, 80F; mean age 61.66 +/- 18.42) with erysipelas hospitalized in the Departments of Dermatology (55 patients-33%) and Infectious Diseases (111 patients-66%) during 2005-2009. The diagnosis was established on clinical and biological data. In these patients clinical and biological exam has been performed. We assessed GFR and urinalysis (hematuria and proteinuria). The control group consisted of 110 apparently healthy persons. Of the 166 patients with erysipelas we found asymptomatic urinary abnormalities in 82 (47%), isolated proteinuria in 19 (11%) patients and proteinuria associated with hematuria in 21 (13%) patients, and isolated hematuria in 38 (23%) patients. We did not find patients with nephrotic or nephritic syndrome. In the control group we found asymptomatic urinary abnormalities in 25 (23%) of the patients. A statistically significant difference was between the two groups (p < 0.01). Asymptomatic urinary abnormalities have been more frequent in patients with erysipelas from the Infectious Diseases Department compared to those from the Dermatology Department. A statistically significant difference has been found (p < 0.03). In patients with recurrent erysipelas (43 patients-26%) we found asymptomatic urinary abnormalities in 26 (54%) of the patients compared to the presence of asymptomatic urinary abnormalities in patients with acute erysipelas in 56 out of 123 (46%). Mean GFR in patients with erysipelas was of 73.94 +/- 27.79 ml/min. It was lower in patients with recurrent erysipelas, 72.13 +/- 24.74 mL/min respectively. Association of proteinuria with hematuria was more frequent in patients with recurrent erysipelas. Patients with asymptomatic urinary abnormalities during the course of erysipelas need to be closely monitored during antibiotic treatment.