A large French multicenter retrospective series of T1-T2N0 vocal cords carcinomas treated with exclusive irradiation.

PURPOSE: The main objective of this study was to evaluate the 5-year efficacy of exclusive laryngeal radiotherapy without node prophylactic irradiation for localized cancers of the vocal cords. PATIENTS AND METHODS: We retrospectively reviewed charts from 258 patients with T1-T2N0 glottic carcinoma irradiated from April 1987 to March 2015 in four France western centers, including pretreated patients. Toxicity was analyzed according to CTCAE v4.0 classification. RESULTS: The median follow-up was 50 months. The median age was 67 years with 87% men and 85.5% had T1 tumor. Five years overall survival was 77.5% (95% confidence interval [95% CI]: 71.4-83.5), 5 years local control was 86.8% (95% CI: 82.3-91.3), specific survival rate was 95% (95% CI: 92.2-97.9) and final laryngectomy-free survival was 87.5% (95% CI: 82.2-92.9). Most toxicities were grade 1 and 2. Grade 3 acute toxicity was 15.5% for the radiation laryngitis, 3.5% for radiodermatitis and 7.7% for dysphonia. Grade 3 chronic toxicity was 3.5% for dysphonia and there were two cases of tracheal stenosis treated by tracheotomy. CONCLUSION: Radiotherapy provides good results in local control of stage I and II vocal cords cancers as well as the toxicity level.

Toxicity and efficacy of cetuximab associated with several modalities of IMRT for locally advanced head and neck cancer.

PURPOSE: Intensity-modulated radiation therapy (IMRT) has shown its interest for head and neck cancer treatment. In parallel, cetuximab has demonstrated its superiority against exclusive radiotherapy. The objective of this study was to assess the acute toxicity, local control and overall survival of cetuximab associated with different IMRT modalities compared to platinum-based chemotherapy and IMRT in the ARTORL study (NCT02024035). PATIENTS AND METHOD: This prospective, multicenter study included patients with epidermoid or undifferentiated nasopharyngeal carcinoma, epidermoid carcinoma of oropharynx and oral cavity (T1-T4, M0, N0-N3). Acute toxicity, local control and overall survival were compared between groups (patients receiving cetuximab or not). Propensity score analysis at the ratio 1:1 was undertaken in an effort to adjust for potential bias between groups due to non-randomization. RESULTS: From the 180 patients included in the ARTORL study, 29 patients receiving cetuximab and 29 patients treated without cetuximab were matched for the analysis. Ten patients (34.5%) reported acute dermal toxicity of grade 3 in the cetuximab group versus three (10.3%) in the non-cetuximab group obtained after matching (P=0.0275). Cetuximab was not significantly associated with more grade 3 mucositis (P=0.2563). There were no significant differences in cutaneous or oral toxicity for patients treated with cetuximab between the different IMRT modalities (P=1.000 and P=0.5731, respectively). There was no significant difference in local relapse-free survival (P=0.0920) or overall survival (P=0.4575) between patients treated with or without cetuximab. CONCLUSION: Patients treated with cetuximab had more cutaneous toxicities, but oral toxicity was similar between groups. The different IMRT modalities did not induce different toxicity profiles.

[Clinical and paraclinical follow-up after radiotherapy for head and neck cancer]. / Suivi clinique et paraclinique après radiothérapie pour un cancer des voies aérodigestives supérieures.

Head and neck cancer management often involves heavy multimodal treatments including radiotherapy. Despite the improvement of intensity-modulated radiation therapy, acute and late toxicities remain important. After such treatment, patients have to face different potential problems, depending on the post-therapeutic delay. In this way, short-term follow-up permits to appreciate the healing of acute toxicities and response to treatment. Long-term follow-up aims to recognize second primitive tumours and distant failure, and to detect and manage late toxicities. Medical and psychosocial supportive cares are essential, even after several years of complete remission. The objective of this article is to review the modalities of short-term and long-term follow-up of patients who receive a radiotherapy for head and neck cancer.

Partial laryngectomy as salvage surgery after radiotherapy: oncological and functional outcomes and impact on quality of life. A retrospective study of 20 cases.

UNLABELLED: The gold standard for the management of laryngeal squamous cell carcinoma in a previously irradiated patient is "salvage" total laryngectomy, but surgical management by partial laryngectomy can sometimes be proposed in selected patients. OBJECTIVES: This study was designed to review the functional and oncological outcomes of patients treated by open partial laryngectomy for recurrent squamous cell carcinoma after failure of radiotherapy or involving previously irradiated tissues and to define prognostic criteria for the selection of patients eligible for this treatment strategy. MATERIALS AND METHODS: In this retrospective study, 20 patients underwent partial laryngectomy between 2000 and 2011 for recurrence or second primary stage I or II laryngeal squamous cell carcinoma in an irradiated territory (11 vertical partial laryngectomies; 9 horizontal partial laryngectomies). RESULTS: The 3-year overall survival rate in patients with negative resection margins was 66%, with higher survival rates for tumours confined to the glottis, and the 2-year local control rate was 67%. Positive resection margins requiring total laryngectomy were observed in 20% of cases. The 3-year overall survival rate was 56% in these patients. Exclusive oral feeding was restored in 75% of patients after an average of 32 days. The tracheotomy tube was removed after an average of 18 days in 90% of patients. The disease-free functional larynx preservation rate was 45%. CONCLUSIONS: Salvage partial laryngectomy in irradiated tissues is an alternative treatment option to total laryngectomy in selected patients.

[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.

Conservation of salivary function and new external head and neck radiation techniques.

INTRODUCTION: New radiation therapy techniques seek to adapt dose distribution to three-dimensional tumor geometry, so as to deliver the lowest possible dose to normal tissue and at-risk organs. This is expected to enhance locoregional control and survival and to reduce complications and thereby improve quality of life. Post-radiation xerostomia significantly deteriorates quality of life. MATERIAL AND METHODS: New external radiation techniques (such as intensity-modulated conformal radiation therapy, RapidArc VMAT arc therapy, tomotherapy, CyberKnife(®), protontherapy, use of carbon ions) applicable in ENT are reviewed. RESULTS: Preliminary data show interesting results in terms of salivary function with highly conformal techniques. CONCLUSION: In France, assessment is ongoing, financed under the Health Ministry's "Support for Expensive Innovatory Techniques" scheme (STIC [Soutien aux techniques innovantes coûteuses]), as routine use is growing rapidly.

Long-term quality of life in patients with rectal cancer treated with preoperative (chemo)-radiotherapy within a randomized trial.

PURPOSE: Few studies have evaluated the quality of life (QoL) of patients with rectal cancer. This report describes the quality of life of French patients who entered the 22921 EORTC trial that investigated the role and place of chemotherapy (CT) added to preoperative radiotherapy (preop-RT). PATIENTS AND METHODS: Patients without recurrences were evaluated with EORTC QLQ-C30 and QLQ-CR38 questionnaires, after a median time of 4.6 years from randomisation. RESULTS: All the scores of QLQ-C30 functions were high, from 78 up to 88, with those of global health quality of life scale (GHQL) status being 73. The mean scores of symptoms were low except for diarrhoea. For QLQ-CR38, the mean scores for "body image" and "future perspective" were high at 79.6 and 69.7 respectively. The scores for "sexual functioning" and "enjoyment" were low. Men had more sexual problems than females (62.5 vs 25 mean scores respectively). Chemotherapy was associated with more diarrhoea complaints, lower "role", lower "social functioning" and lower global health quality of life scale. CONCLUSION: The overall quality of life of patients with rectal cancer is quite good 4.6 years after the beginning preoperative treatments. However, adding chemotherapy to preoperative radiotherapy has a negative effect on diarrhoea complaints and some quality of life dimensions.

[Central toxic keratopathy and fibromyalgia: a case report]. / Kératopathie centrale toxique et fibromyalgie : à propos d'un cas.

INTRODUCTION: A patient with fibromyalgia after laser refractive surgery presented bilateral diffuse lamellar keratitis complicated by central toxic keratopathy. CLINICAL CASE: A 51-year-old patient, followed for fibromyalgia, consulted for visual loss 1 week after laser in situ keratomileusis. Slit lamp examination revealed stromal infiltrate in both eyes into the flap interface. Confocal microscopy showed an infiltration of inflammatory cells into the anterior stroma and the flap interface. Intensive topical corticosteroid treatment was used and the left eye was treated with flap lifting and interface irrigation. The corneal infiltrates decreased very slowly, and the left eye developed postoperative hyperopia. Diagnosis of central toxic keratopathy was discussed. Visual acuity, highly volatile, was limited to 7/10 (right eye) and 6/10 (left eye). CONCLUSION: Diffuse lamellar keratitis (DLK) is a sterile inflammation after laser in situ keratomileusis. Central toxic keratopathy is characterized by noninflammatory central corneal opacification with a significant hyperopic shift. The cause of central toxic keratopathy is unknown. Fibromyalgia is a widespread, chronic pain disorder that includes a complex constellation of somatic and emotional symptoms. Patients often complain of dry eye sensations. Recent studies have highlighted a reduced corneal sensitivity in patients with fibromyalgia. There could be a relation between fibromyalgia, diffuse lamellar keratitis, and central toxic keratopathy. Some precautions may be used before LASIK in patients with fibromyalgia.

[Perioperative interstitial brachytherapy for recurrent keloid scars]. / La curiethérapie interstitielle périoperatoire dans le traitement des cicatrices chéloïdes récidivantes.

PURPOSE: Evaluation of the results of perioperative interstitial brachytherapy with low dose-rate (LDR) Ir-192 in the treatment of keloid scars. PATIENTS AND METHODS: We performed a retrospective analysis of 73 histologically confirmed keloids (from 58 patients) resistant to medicosurgical treated by surgical excision plus early perioperative brachytherapy. All lesions were initially symptomatic. Local control was evaluated by clinical evaluation. Functional and cosmetic results were assessed in terms of patient responses to a self-administered questionnaire. RESULTS: Median age was 28 years (range 13-71 years). Scars were located as follows: 37% on the face, 32% on the trunk or abdomen, 16% on the neck, and 15% on the arms or legs. The mean delay before loading was four hours (range, 1-6h). The median dose was 20Gy (range, 15-40Gy). Sixty-four scars (from 53 patients) were evaluated. Local control was 86% (follow-up, 44.5 months; range, 14-150 months). All relapses occurred early - within 2 years posttreatment. At 20 months, survival without recurrence was significantly lower when treated lengths were more than 6cm long. The rate was 100% for treated scars below 4.5cm in length, 95% (95% CI: 55-96) for those 4.5-6cm long, and 75% (95% CI: 56-88) beyond 6cm (p=0.038). Of the 35 scars (28 patients) whose results were reassessed, six remained symptomatic and the esthetic results were considered to be good in 51% (18/35) and average in 37% (13/35) (median follow-up, 70 months; range, 16-181 months). CONCLUSION: Early perioperative LDR brachytherapy delivering 20Gy at 5mm reduced the rate of recurrent keloids resistant to other treatments and gave good functional results.

[Locally advanced head and neck cancers: recommendations of an expert panel and perspectives for the use of TPF regimen (docetaxel, cisplatin and fluoro-uracil) as induction therapy]. / Cancers des voies aérodigestives supérieures (VADS) localement avancés: recommandations d'un panel d'experts et de perspectives pour l'utilisation du schéma TPF (docétaxel, cisplatine, 5-fluoro-uracile) en induction.

PURPOSE: The purpose of the present article was to evaluate indications, regimens, treatment modalities, and predictive factors of response to treatment in locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: An expert panel including otolaryngology and head and neck surgery specialists, oncologists, radiotherapists and biologists analyzed the literature providing a synthesis and giving some recommendations. SYNTHESIS: Findings from the main randomized phase III trials highlight that the TPF regimen (docetaxel, cisplatin, fluorouracil) represent a preferential option when induction chemotherapy is indicated in either operable or non-operable patients. Given the potential fragility of patients presenting with SCCHN, treatment modalities in routine use require applying preventive measures and tailored follow-up according to each patient's profile. As regards predictive factors of response to TPF regimen, no factor is currently validated, but ongoing trials should provide better knowledge. CONCLUSION: Progresses in induction chemotherapy have allowed improving the prognosis of patients with locally advanced SCCHN. The TPF regimen represents a major improvement in this indication, and ongoing strategic clinical trials should refine its indications.

Phase 3 randomized trial on larynx preservation comparing sequential vs alternating chemotherapy and radiotherapy.

BACKGROUND: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. METHODS: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3-T4) or hypopharynx (T2-T4), with regional lymph nodes in the neck staged as N0-N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The Kaplan-Meier method was used to obtain time-to-event data. RESULTS: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. CONCLUSIONS: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Negative influence of delayed surgery on survival after preoperative radiotherapy in rectal cancer.

OBJECTIVE: In Europe, until recently the standard treatment for locally advanced rectal cancer was preoperative radiotherapy (RT). The objective of this study was to evaluate the influence on survival of intervals between diagnosis and treatment. PATIENTS AND METHODS: The influence on survival of intervals between diagnosis and surgery (Dg-Surg), diagnosis and initiation of RT (Dg-Rad), and completion of RT and surgery (Rad-Surg) was evaluated in a retrospective series of patients treated with preoperative RT. Between 1991 and 1998, 102 patients received treatment with preoperative RT without concomitant chemotherapy at the René Gauducheau Cancer Center. Patients generally received 45 Gy (80%) in 25 fractions over 35 days for T2-T3-T4 N0-N1 M0 rectal adenocarcinoma located mainly (62.7%) in the lower third of the rectum (< or = 5 cm from anal margin). Thirty-five pN1 patients were treated with postoperative chemotherapy. Differences between survival were assessed by the log-rank test, and prognostic factors by the Cox test. RESULTS: Median time was 14.7 weeks for Dg-Surg, 4.6 weeks for Dg-Rad and 5.1 weeks for Rad-Surg. Median follow-up from diagnosis was 57.4 months. Five-year local relapse-free survival was 83.9%, metastasis-free survival 64% and overall survival 60.8%. No factor was predictive of tumour response to RT. Log-rank and multivariate analysis showed that overall survival was significantly influenced by lower-third tumours, pT, pN and Dg-Surg (poorer survival when > or = 16 weeks: OR = 2.59, P = 0.005). Metastasis-free survival correlated significantly with Dg-Surg (> or = 16 weeks: OR = 2.05, P = 0.05). CONCLUSION: An interval of more than 16 weeks between diagnosis and surgery may reduce overall survival of patients treated with preoperative RT for locally advanced rectal cancer. Surgery should be performed shortly after completion of RT for patients with no possibility of sphincter preservation, or a minimal risk of morbidity from an abdominoperineal excision.

[Interstitial brachytherapy of peri-orificial skin carcinomas on the face]. / Curiethérapie interstitielle des cancers cutanés des zones périorificielles de la face.

Purpose. - To analyse 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 (BCCs), 9 squamous cell carcinomas (SCCs)) 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 [50-65] in group 1 and 52 Gy [50-60] 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 [17-97]. 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 [6-132]). Five-year disease-free survival was better in group 1 (91% [75-97]) than in group 2 (80% [62-90]), P=0.23. Of the 34 patients whose results were re-assessed, eight presented pruritus or epiphora. One 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) of good results and 28 (3/11) vs. 43% (10/23) of fair results. Conclusion. - 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.

[Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)]. / Proposition de sélection et délimitation des volumes cibles microscopiques péritumoraux dans les cancers de la cavité buccale et de l'oropharynx (aires ganglionnaires exclues).

This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.

Concomitant radiochemotherapy or accelerated radiotherapy: analysis of two randomized trials of the French Head and Neck Cancer Group (GORTEC).

In the early 1990s, when conventional radiotherapy (RT) was the standard of care in patients with locally advanced head and neck squamous cell carcinoma (HNSCC), two main options were being tested to improve the efficacy and the therapeutic ratio of RT. The first approach evaluated the effect of adding chemotherapy (CT) simultaneously to RT (RT-CT), while the second approach assessed the effect of modified fractionated RT. To answer these two questions, in 1994, the French Group for Head and Neck Oncology Radiotherapy (GORTEC) initiated two randomized trials. A total of 494 patients were entered in these two parallel phase III multicenter trials comparing conventional RT (70 Gy in 35 fractions) either with concomitant RT-CT (226 patients; 70 Gy in 35 fractions with three cycles of a 4-day regimen comprising carboplatin and 5-fluorouracil [5FU]) or with very accelerated RT (268 patients) delivering 64 Gy in 3 weeks. The 5-year overall survival (OS), specific disease-free survival (DFS), and local-regional control rates were improved in favor of simultaneous RT-CT, whereas local-regional control was significantly improved with accelerated RT, along with a marginal effect on OS and DFS. This increased antitumor efficacy was in both cases associated with a marked increase in acute RT-induced toxicity, which was more pronounced with accelerated RT, whereas late effects were marginally increased with the addition of CT and not influenced by accelerated RT. We conclude that both concomitant RT-CT and accelerated RT improved tumor control rates, as compared to conventional RT, along with increased but manageable toxicity. The two regimens are currently being tested in an ongoing randomized study and also being compared to moderately accelerated RT and concomitant CT.

Preoperative chemoradiotherapy versus preoperative radiotherapy in rectal cancer patients: assessment of acute toxicity and treatment compliance. Report of the 22921 randomised trial conducted by the EORTC Radiotherapy Group.

The European Organisation for Research and Treatment of Cancer (EORTC) 22921 four-arm randomised trial questioned the value of preoperative chemoradiation (XRT-CT) versus preoperative radiation (XRT) and the value of additional postoperative chemotherapy (CT) versus none in T3-T4 M0 resectable rectal cancer patients. We report on the preoperative toxicity, treatment compliance and early deaths (all deaths up to 30 days after surgery) of the two treatment modalities in patients who were entered into trial before January 2001. In the XRT Group (group A), patients received 45 Gy, 25 fractions over 5 weeks. In the XRT-CT Group (group B), two 5-day courses of CT were added to the first and fifth weeks of XRT. For each CT course: 5-fluorouracil (5-FU) 350 mg/m2/day and Leucovorin (LV) 20 mg/m2/day were given. 398 and 400 patients started treatment in groups A and B, respectively. Grade 2+acute diarrhoea occurred in 17.3 and 34.3% of patients in groups A and B, respectively (P<0.005). The other side-effects remained unchanged or were only marginally increased. The compliance with RT was 98.5 and 95.5% in groups A and B, respectively. In group B, 78.7 and 71.1% of the patients received 95-105% of the planned CT doses at the first and second courses, respectively. 6 patients died preoperatively, 2 from toxicity in group B. 8 patients (1%) died within the 30 days after surgery in both groups. At the doses recommended in the protocol, the addition of 5-FU-LV to preoperative XRT slightly increased the amount of acute toxicity. However, the compliance with the radiation protocol or the feasibility of surgery did not decrease.