Oncological and functional outcomes for transoral robotic surgery following previous radiation treatment for upper aerodigestive tract head and neck cancers. A French multicenter GETTEC group study.

BACKGROUND: Transoral robotic surgery (TORS) opens new perspectives. We evaluated the outcomes for patients having undergone TORS after previous radiotherapy. METHODS: A retrospective multicenter study (n = 138) in a previously irradiated area between 2009 and 2020. Survival was assessed with the Kaplan-Meier method. Prognostic factors were evaluated using a chi-squared test, Fisher's test, or Wilcoxon's test. RESULTS: The median length of hospital stay was 12.5 days. Bleeding was the most frequent postoperative complication (15.2%, n = 22). Prophylactic vessel ligation did not significantly decrease bleeding. Complications were significantly lower for Tis, T1, and N0 tumors. 91.6% (n = 120) of the patients with a perioperative tracheotomy could be decannulated. Larynx was functional for 65.94% of the patients. The median length of follow-up was 26 months. The 5-year overall and relapse-free survival rates were respectively 59.9% and 43.4%. CONCLUSION: Oncological and functional results confirmed the value of TORS as a treatment in previously irradiated area.

A Novel Absorbable Stapler Provides Patient-Reported Outcomes and Cost-Effectiveness Noninferior to Subcuticular Skin Closure: A Prospective, Single-Blind, Randomized Clinical Trial.

BACKGROUND: Deep dermal suturing is critical for scar quality outcomes. The authors evaluated a new, fast medical device for dermal suturing, with the hypothesis of noninferiority with regard to clinical scar and cost-effectiveness. METHODS: A prospective, patient-blind, randomized, multicenter noninferiority study in 26 French hospitals was conducted. Patients were randomized 1:1 to suturing with conventional thread or a semiautomatic stapler. The Patient Scar Assessment Scale was rated at 3 months for primary endpoint effectiveness. Secondary endpoints were cost-effectiveness of the two suturing methods, prevalence of complications, suturing/operating time, Observer Scar Assessment Scale and Patient Scar Assessment Scale score, scar aesthetic quality 18 months after surgery, and occupational exposure to blood during surgery. RESULTS: Six hundred sixty-four patients were enrolled, 660 were randomized, and 649 constituted the full analysis (stapler arm, n = 324; needle arm, n = 325). Primary endpoint Patient Scar Assessment Scale score in the stapler arm was not inferior to that in the needle arm at 3 months or after 18 months. The mean operating time was 180 minutes in the stapler arm and 179 minutes in the needle arm (p = not significant). The mean suturing time was significantly lower in the stapler arm (p < 0.001). There were seven occupational exposures to blood in the needle arm and one in the stapler arm. The two arms did not differ significantly in terms of complications (p = 0.41). The additional cost of using the device was &OV0556;51.57 for the complete-case population. CONCLUSION: Wound healing outcome was no worse than with conventional suturing using a semiautomatic stapler and associated with less occupational exposure to blood. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, I.

Oncological and functional outcomes of trans-oral robotic surgery for pyriform sinus carcinoma: A French GETTEC group study.

BACKGROUND: Pyriform sinus carcinomas (SCC) present specific functional and oncological issues. The recent advent of trans-oral robotic surgery (TORS), as a conservative procedure, has opened up new perspectives. OBJECTIVES: To present the oncological and functional outcomes of TORS for pyriform sinus SCC. MATERIALS AND METHODS: We included, retrospectively, all TORS procedures for pyriform sinus SCC performed between 2009 and 2017 in eight French tertiary referral centers. We excluded lesions involving the pyriform sinus that had developed from the oropharynx, larynx, or other anatomic sub-sites of the hypopharynx. RESULTS: We included 57 TORS procedures. Median hospital stay was 10 days. A preventive tracheotomy was performed in seven cases (12%), and all were successfully decannulated. Oral re-feeding was possible for 93%, after a median of 5 days. The main surgical complications were hemorrhages (three cases), all successfully handled, although 2 patients with heavy comorbidities died from blood loss in the days after. Adjuvant therapy was proposed in 31 cases (54%), including two cases of salvage surgery (total pharyngolaryngectomy). After a median follow-up of 23 months, overall and disease-free survival were, respectively, 84% and 74% at 24 months, and 66% and 50% at 48 months. At the end of follow-up, organ preservation rate was 96%. None of the surviving patients needed a tracheotomy and oral diet was possible for 96%. CONCLUSION: The functional and oncological outcomes of TORS for pyriform sinus cancer are encouraging, and this procedure can be considered safe for selected early or moderately advanced cases as a conservative treatment.

Randomized trial comparing two methods of re-irradiation after salvage surgery in head and neck squamous cell carcinoma: Once daily split-course radiotherapy with concomitant chemotherapy or twice daily radiotherapy with cetuximab.

BACKGROUND: A previous randomized trial in recurrent Head and Neck squamous-cell carcinoma (HNSCC) has shown re-irradiation combined with chemotherapy after salvage surgery significantly improved disease-free survival (DFS). The objective of this randomized trial was to compare two methods of re-irradiation in terms of toxicity and survival. PATIENTS AND METHODS: Patients with recurrence/second primary in previously irradiated area were randomly allocated to receive either 60 Gy over 11 weeks with concomitant 5FU - hydroxyurea (VP-arm), or 60 Gy (1.2 Gy twice daily) over 5 weeks with cetuximab (HFR-arm). Primary endpoint was treatment interruption >15 days (acute toxicity). RESULTS: Twenty-six patients were included in VP-arm and 27 in HFR-arm. One patient in VP-arm experienced >15 days interruption due to toxicity, and none in HFR-arm. In both arms, all patients received at least 60 Gy. In VP-arm, 8/26 patients had chemotherapy delay and/or dose reduction. In HFR-arm, 4/27 patients had <6 cycles cetuximab. There was no significant difference in overall survival (Median OS: 37.4 months vs 21.9 months, p = 0.12). Toxicities and DFS were not different between 2 arms. CONCLUSIONS: Twice daily schedule of re-irradiation of 60 Gy/5 weeks with cetuximab was tolerable and no significant difference in treatment delays occurred between two arms.

Cervical spondylodiscitis following an invasive procedure on the neopharynx after circumferential pharyngolaryngectomy: a retrospective case series.

PURPOSE: To highlight cervical spondylodiscitis as an infrequent complication following an invasive procedure on the neopharynx in patients previously treated with circumferential pharyngolaryngectomy with pectoralis major myocutaneous flap reconstruction. METHODS: Patients diagnosed with cervical spondylodiscitis after circumferential pharyngolaryngectomy between 2001 and 2013 were retrospectively studied using a questionnaire sent to the French head and neck tumour study group. Medical history; tumour management; clinical symptoms; biological, microbiological and imaging results; and management of the infection were collected for each patient. RESULTS: Six men aged 51-66 years were diagnosed with spondylodiscitis on average 5.6 years after circumferential pharyngolaryngectomy, and a mean 2 months following an invasive procedure on the neopharynx (oesophageal dilatation, phonatory prosthesis insertion). The patients presented with cervical pain and increased CRP level. MRI showed epidural abscess and communication between the pharynx and vertebral bodies in most cases. Microbiological samples yielded bacteria from the pharynx flora. Infection was managed using antibiotics adjusted according to the culture results and spinal immobilisation for duration of 6-12 weeks. No surgical treatment was required. During follow-up, no patient experienced recurrence or residual disability. CONCLUSIONS: Cervical spondylodiscitis is a rare but potentially severe complication following an invasive procedure on the neopharynx after circumferential pharyngolaryngectomy. Therefore, the onset of nonspecific symptoms should not be overlooked, and MRI must be performed if infection is suspected. Microbiological confirmation is critical in optimising treatment, which should be aggressive, even if overall prognosis seems to be good.

Postoperative interstitial brachytherapy for resectable squamous cell carcinoma of the tongue.

PURPOSE: To evaluate the efficiency and toxicity of postoperative brachytherapy (POBT) in the treatment of resectable mobile tongue squamous cell carcinoma. PATIENTS AND METHODS: This was a retrospective single-center study of patients with SSC of the mobile tongue who were treated between August 1992 and June 2013 by glossectomy and neck dissection followed by (192)Ir interstitial brachytherapy of the tumor bed. Endpoints were local control, cancer-specific survival (CSS), overall survival (OS), and morbidity. Independent prognostic factors were analyzed in a Cox regression model. RESULTS: A total of 112 patients were identified (median age, 55 years [range, 15-84]; 76% male). Patient and tumor characteristics were: T1T2N0 (85%), pN+ (13%), positive surgical margins (14%), negative margins <5 mm (29%), dysplasic margins (14%), lymphatic vessel invasion (5%), and perineural spread (5%). Median followup was 6.7 years (1.5 months to 17.7 years). Local control, CSS, and OS rates at 2 years were 79%, 81%, and 72%, respectively. The corresponding 5-year rates were 76%, 67%, and 56%, respectively. After POBT, 22% of patients presented grade ≥2 necrosis and 8% experienced chronic pain. Independent prognostic factors were positive surgical margins for poor local control and tumor recurrence and lymphatic vessel invasion for poor OS. CONCLUSION: POBT provided good local control and better CSS and OS than reported for surgery alone. Morbidity was higher than that reported for brachytherapy alone but may be considered acceptable in a well-selected patient population at high risk of local recurrence.

Results after U-shaped pectoralis major myocutaneous flap reconstruction of circumferential pharyngeal defects.

OBJECTIVES/HYPOTHESIS: To evaluate surgical, functional, carcinologic results after circumferential pharyngolaryngectomy and reconstruction with U-shaped pectoralis major myocutaneous flap. STUDY DESIGN: Retrospective case series. METHODS: Forty-one patients included spanning a 6-year period. RESULTS: General and local complications occurred in 10% and 22% of patients respectively, without early death. Swallowing and vocal functions were satisfactory for 82% and 43% of patients respectively, despite 39% of neopharynx stricture and 22% of pharyngocutaneous fistula. With a 20-month mean follow-up, cancer recurrence was present in 58% of patients. The overall survival rate was 29% at 3 years. CONCLUSIONS: This flap is simple, reliable, and allows adequate reconstruction of the hypopharynx. However, the neopharynx stricture rate is high and the quality of voice rehabilitation is poor when compared with free flaps. This procedure, which is an option for the reconstruction of circumferential pharyngeal defects, must be considered in selected cases.

Relevance of both individual risk factors and occupational exposure in cancer survival studies: the example of intestinal type sinonasal adenocarcinoma.

OBJECTIVES/HYPOTHESIS: Wood dust is a well-established risk factor for intestinal type sinonasal adenocarcinoma. The 5-year overall survival has varied from 20% to 80% according T1-T4 stages; 5-year survival according to histologic subtype has varied from 20% to 50%. To date, no study has evaluated whether environmental, occupational, and personal risk factors have any impact on both overall and cancer-specific survival. We aimed to determine whether exposure to carcinogenic risk factors besides wood exposure can influence the survival of patients with sinonasal ethmoid carcinoma. STUDY DESIGN: Retrospective cohort study of the association of survival data and occupational and personal carcinogenic risk factors. METHODS: All patients hospitalized for ethmoid adenocarcinoma at the Nantes University Hospital between 1988 and 2004 were included . Data concerning TNM classification, histology, type and quality of tumor resection at the macro- and microscopic level, and occupational and personal exposure to carcinogens were collected. Statistical analysis was conducted using univariate and multivariate linear regression. RESULTS: A total of 98 patients were included with a response rate of 98%. Data showed 86% of patients had been exposed to wood dust. The 5-year survival was 62%. We first identified four factors that independently influenced overall survival: diplopia (P = .0159), spread to the orbit (P = .0113), bilateral involvement (P = .0134), TNM stage (P < .001). When the analysis included all occupational environmental factors (wood dust, solvent, and metals exposure) as well as personal risk factors, the length of exposure to metals (P = .0307) and tobacco exposure (P = .0031) also were found to influence 5-year overall survival. We identified high prevalence of colon cancer (4%) and double cancer (18%). CONCLUSIONS: We showed exposure to both environmental (tobacco) and occupational (metal dust) factors could influence survival in the diagnosis of a cancer. Our study suggests that screening for colon cancer should be offered to wood dust workers. A prospective multicentric study should be necessary to confirm our results.

Prognostic factors for T1-T2 squamous cell carcinomas of the mobile tongue: A retrospective cohort study.

BACKGROUND: The aim of this study was to identify factors predicting poor prognosis at the time of early oral tongue carcinoma diagnosis. METHODS: A retrospective cohort study was carried out on 70 patients with T1 or T2 squamous cell carcinoma of the mobile tongue treated with primary surgical treatment. RESULTS: In all, 47% of patients received adjuvant treatment. Local recurrence was observed in 29% and regional recurrence in 26%. With a median follow-up of 7.3 years for living patients, 5-year actuarial overall, disease-specific, and disease-free survival rates were 48%, 61%, and 42%, respectively. The presence of poor histological differentiation increased the overall risk of death. Tumor thickness and posterior lingual location independently increased overall and disease-specific risk of death. Concurrent or previous diagnosis of oral lichen significantly increased the risk of disease-specific death and disease recurrence. CONCLUSIONS: This study corroborates several known prognostic factors and indicates that diagnosis of oral lichen planus may be a risk factor for disease recurrence.

Role of radiotherapy in the treatment of nasoethmoidal adenocarcinoma.

OBJECTIVE: To assess the efficacy of radiotherapy in the treatment of nasoethmoidal adenocarcinoma. DESIGN: Multicenter, retrospective study. SETTING: Eleven French hospitals. PATIENTS: The medical records of 418 patients who presented with nasoethmoidal adenocarcinoma from January 1, 1976, through December 31, 2001, were evaluated. A total of 324 patients were treated with a combination of surgery and radiotherapy, and 55 were treated with surgery only. MAIN OUTCOME MEASURES: Survival rates, disease recurrence, and postoperative complications. RESULTS: The 5-year Kaplan-Meier survey revealed survival rates of 64.5% for the surgery-only group and 70.8% for the combined-treatment group. In the surgery-only group, 28 patients (51%) had disease recurrence (24 local, 2 regional, and 2 distant). Of the 55 patients in the combined-treatment group, 31 patients (56%) had disease recurrence (29 local, 1 regional, and 1 distant). Immediate postoperative complications in the combined-treatment group were hemorrhages in 2 patients, meningitis in 3 patients, and cerebrospinal fluid leakage in 4 patients, but no deaths occurred. In the surgery-only group, 1 patient had meningitis, 2 had cerebrospinal fluid leaking but no hemorrhage, and 5 died postoperatively. CONCLUSION: The results of this retrospective study suggest that radiotherapy can be used to treat nasoethmoidal adenocarcinoma, but its usefulness should be confirmed with further prospective studies.

Gene expression profiling in sinonasal adenocarcinoma.

BACKGROUND: Sinonasal adenocarcinomas are uncommon tumors which develop in the ethmoid sinus after exposure to wood dust. Although the etiology of these tumors is well defined, very little is known about their molecular basis and no diagnostic tool exists for their early detection in high-risk workers. METHODS: To identify genes involved in this disease, we performed gene expression profiling using cancer-dedicated microarrays, on nine matched samples of sinonasal adenocarcinomas and non-tumor sinusal tissue. Microarray results were validated by quantitative RT-PCR and immunohistochemistry on two additional sets of tumors. RESULTS: Among the genes with significant differential expression we selected LGALS4, ACS5, CLU, SRI and CCT5 for further exploration. The overexpression of LGALS4, ACS5, SRI, CCT5 and the downregulation of CLU were confirmed by quantitative RT-PCR. Immunohistochemistry was performed for LGALS4 (Galectin 4), ACS5 (Acyl-CoA synthetase) and CLU (Clusterin) proteins: LGALS4 was highly up-regulated, particularly in the most differentiated tumors, while CLU was lost in all tumors. The expression of ACS5, was more heterogeneous and no correlation was observed with the tumor type. CONCLUSION: Within our microarray study in sinonasal adenocarcinoma we identified two proteins, LGALS4 and CLU, that were significantly differentially expressed in tumors compared to normal tissue. A further evaluation on a new set of tissues, including precancerous stages and low grade tumors, is necessary to evaluate the possibility of using them as diagnostic markers.

Randomized trial of postoperative reirradiation combined with chemotherapy after salvage surgery compared with salvage surgery alone in head and neck carcinoma.

PURPOSE: Full-dose reirradiation combined with chemotherapy has been shown to be feasible after salvage surgery with acceptable toxicity. The Groupe d'Etude des Tumeurs de la Tête et du Cou and Groupe d'Oncologie Radiothérapie Tête Et Cou groups performed a randomized study to assess its efficacy. PATIENTS AND METHODS: Between 1999 and 2005, 130 patients with head and neck cancer were treated with salvage surgery and randomly assigned to full-dose reirradiation combined with chemotherapy (RT arm) or to observation (a "wait and see" approach; WS arm). Eligibility criteria were recurrence or a second primary tumor in a previously irradiated area, no major sequelae resulting from the first radiotherapy, good general condition, no distant metastasis, and salvage surgery with macroscopic complete resection. Patients in the RT arm received 60 Gy over 11 weeks combined with concomitant fluorouracil and hydroxyurea. RESULTS: Sixty-five patients were randomly assigned to each arm. There was no imbalance in the distribution of the main tumor and patients characteristics. The most serious acute toxicity in the RT arm was mucositis, attaining grade 3 or 4 in 28% of patients. At 2 years, 39% of patients in the RT arm and 10% in the WS arm experienced grade 3 or 4 late toxicity according to Radiation Therapy Oncology Group criteria (P = .06). Disease-free survival (DFS) was significantly improved in the RT arm, with a hazard ratio of 1.68 (95% CI, 1.13 to 2.50; P = .01), but overall survival (OS) was not statistically different. CONCLUSION: Full-dose reirradiation combined with chemotherapy after salvage surgery significantly improved DFS, but had no significant impact on OS. An increase in both acute and late toxicity was observed.

Adenocarcinoma of Ethmoid: a GETTEC retrospective multicenter study of 418 cases.

OBJECTIVE: To determine risk factors and evaluate the treatment of ethmoid adenocarcinoma. Epidemiologic data were recorded and compared with the literature. MATERIALS AND METHODS: A multicenter and retrospective study. The medical records of 418 patients who had presented with ethmoid adenocarcinoma at 11 French hospitals from 1976 to 2001 were analyzed to determine the clinical characteristics and treatment of the disease. RESULTS: The gender ratio was 2.8 men per 1 woman. Toxic exposure was classic for this lesion, exposure to wood and leather for most cases. The mean age was 63 years (range 31-91). Symptoms were nonspecific and based on clinical rhinologic signs. Nasal endoscopy after mucosal retraction was found useful to evaluate the extension of the lesion and to perform biopsies. Computed tomography scan and magnetic resonance imagery must be carried out prior to treatment to define extra nasal extension. The survival rate was significantly influenced by the size of the lesion (T4, N+) and extension to brain or dura. Surgery with postoperative radiotherapy remains the treatment of choice. Total excision must be a major priority, as confirmed in our series. CONCLUSION: This retrospective study was, to our knowledge, the largest ever reported in the literature. This series confirmed the risk factor of this lesion as well as the lesion's influence on the survival rate. Surgery is the most important part of the treatment. Local recurrences were responsible for the poor prognosis of this lesion.

Interstitial brachytherapy of periorificial skin carcinomas of the face: a retrospective study of 97 cases.

PURPOSE: To analyze outcomes after interstitial brachytherapy of facial periorificial skin carcinomas. PATIENTS AND METHODS: We performed a retrospective analysis of 97 skin carcinomas (88 basal cell carcinomas, 9 squamous cell carcinomas) of the nose, periorbital areas, and ears from 40 previously untreated patients (Group 1) and 57 patients who had undergone surgery (Group 2). The average dose was 55 Gy (range, 50-65 Gy) in Group 1 and 52 Gy (range, 50-60 Gy) in Group 2 (mean implantation times: 79 and 74 hours, respectively). We calculated survival rates and assessed functional and cosmetic results de visu. RESULTS: Median age was 71 years (range, 17-97 years). There were 29 T1, 8 T2, 1 T3, and 2 Tx tumors in Group 1. Tumors were <2 cm in Group 2. Local control was 92.5% in Group 1 and 88% in Group 2 (median follow-up, 55 months; range, 6-132 months). Five-year disease-free survival was better in Group 1 (91%; range, 75-97) than in Group 2 (80%; range, 62-90; p = 0.23). Of the 34 patients whose results were reassessed, 8 presented with pruritus or epiphora; 1 Group 2 patient had an impaired eyelid aperture. Cosmetic results were better in Group 1 than in Group 2 with, respectively, 72% (8/11) vs. 52% (12/23) good results and 28 (3/11) vs. 43% (10/23) fair results. CONCLUSIONS: Brachytherapy provided a high level of local control and good cosmetic results for facial periorificial skin carcinomas that pose problems of surgical reconstruction. Results were better for untreated tumors than for incompletely excised tumors or tumors recurring after surgery.

Removal of ethmoidal malignant tumors by the isolated paralateronasal approach with resection of the cribriform plate and the dura mater.

OBJECTIVE: A series of ethmoidal tumors was resected by an entirely extracranial approach through a lateral rhinotomy incision, with partial maxillectomy and removal of the cribriform plate and dura mater from below. METHODS: Thirty-four consecutive patients (32 male, 2 female; mean age 64 years, range 45-78) with malignant tumors of the ethmoid sinus were operated by this technique between July 1998 and February 2002. All had complete tumor resection, including the cribriform plate and the dura mater. Excision was performed en bloc 23 times (68%). Although cerebral involvement was encountered in four cases (T4 IC), this technique was adequate for tumor resection, together with corticectomy when necessary. The method used for tumor resection and rebuilding of the anterior skull base is described in detail. RESULTS: There were no immediate postoperative deaths. One patient developed pneumococcal meningitis with cerebrospinal fluid leakage as a result of a technical error and required further surgery. Four patients presented a confusion syndrome that regressed during the hospital stay, 2 complained of transient diplopia, and 4 had hematoma of the abdominal wall. Mean follow-up of 10.4 months (1-41 months) is still too short to reach definitive conclusions about oncologic results. CONCLUSIONS: This approach is particularly suitable for removal of tumors in contact with or invading the cribriform plate. Tumor resection is as extensive as with the traditional mixed approach, but does not require the frontal lobes to be drawn aside.