Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer.

PURPOSE: Roughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. MATERIALS AND METHODS: Eligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint. RESULTS: One hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%-96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5-NR), and median progression-free survival 14.4months (95% CI: 11.2-18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. CONCLUSION: These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.

Management of oropharyngeal squamous cell carcinoma.

This article reviews the various treatment options, by primary or postoperative external radiotherapy and by brachytherapy for the p16-negative oropharyngeal squamous cell carcinoma. Dose levels, fractionation and association with systemic treatments are presented. The need for neck node dissection post local treatment is discussed, as well as specificities for the management of p16-positive tumours. Guidelines for target volume selection and delineation are thoroughly elaborated. Last, the management by radiotherapy of locoregional recurrences is discussed.

Survival comparision of three-dimensional radiotherapy alone with concurrent chemoradiotherapy for non-surgical esophageal carcinoma.

PURPOSE: Radiotherapy is the main treatment method for patients with locally advanced, unresectable esophageal cancer. The aim of this study is to compare overall survival (OS) using 3D radiotherapy (3DRT) alone with concurrent chemoradiotherapy (CCRT) in 296 non-surgical esophageal carcinoma patients. PATENTS AND METHODS: Over 10 years, of the 480 patients with esophageal carcinoma treated with 3DRT with or without chemotherapy, 148 patients each comprised 3DRT and CCRT groups after propensity score matching. RESULTS: The 5- and 10-year OS (P=0.337) and PFS (P=0.715) rates for 3DRT alone were 22.0%, 14.4% and 26.1%, 23.2%, respectively, compared with 28.8%, 18.6% and 34.7%, 29.1% for CCRT, respectively. CCRT did not improve 5-year and 10-year OS or PFS in 60-70Gy group (OS: 27.5% and 25.2%; 17.9% and 17.0%, P=0.938; PFS: 38.3% and 31.8%; 31.9% and 27.8%, P=0.890) nor reduce 10-year hematogenous metastasis (31.7% and 28.3%, P=0.698). CCRT improved 5-year OS and PFS of 50.0-59.9Gy group (OS: 33.3% and 12.0%, P=0.029; PFS: 33.1% and 10.6%, P=0.081). For 3DRT, the 5-year OS and PFS rates were significantly better in the 60-70Gy group (P=0.017) compared with 50.0-59.9Gy group (P=0.002). For CCRT group, 5-year OS and PFS favored the 50.0-59.9Gy group, but the difference was insignificant. Major toxicities were greater with CCRT compared with 3DRT. CONCLUSION: For non-surgical esophageal carcinoma patients, 3DRT combined with CCRT was effective in prolonging both OS and PFS.

[Neoadjuvant chemotherapy in locally advanced cervical cancer in patients receiving a concomitant chemoradiotherapy in a low income country]. / Chimiotherapie neo adjudante dans les cancers localement avances du col uterin chez des patientes recevant une radiochimiotherapie concomitante dans pays aux ressources limitees.

PURPOSE: Delays to access to radiotherapy are long in our context. The purpose of this study was to analyze the effect of neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancers. PATIENTS AND METHODS: We conducted a retrospective study from April 2014 to April 2016 at the radiotherapy center of "Hopital du Mali" in Bamako, Mali. Patients were allocated according to age, histological type, tumor size and the 2002 classification of the FIGO. Experimental protocol was the administration of a neoadjuvante chemotherapy with association of Paclitaxel 175mg/m2 + Carboplatine AUC 5 every 3 weeks and radiothérapy cure with avec linac 6 MV at 70 Gy due to 5 sessions of 2 Gy per week associated with a concomitant chemotherapy with cisplatin at 40 mg/m2/week. The clinical response was assessed at the end of neoadjuvant chemotherapy and of concomitant chemoradiotherapy. RESULTS: Thirty patients were included in the study. The mean age was 53.63 ± 8.9 years. The mean size of the tumor was 5.17 cm (2 to 7 cm). According to the 2002 classification of the FIGO stages IIB were 33% (n = 10); IIIB were 57% (n = 17) and IVA were 10% (n = 3). Clinical evaluation at the end of neoadjuvant chemotherapy found: complete response 17 % (n = 5), partial response 10% (n = 3) and stable disease 73 % (n = 22). Evaluation at the end of the concomitant chemoradiotherapy had found the complete response in 90% (n = 27) and stable disease in 10% (n = 3). CONCLUSION: Neoadjuvant chemotherapy to concomitant chemoradiotherapy in locally advanced cervical cancer allows stabilization of the tumor and improves local control. Due to long delays to access to radiotherapy treatment in our context; neoadjuvant chemotherapy is an alternative to stabilize the disease and prevent distant metastasis from locally advanced cervical cancers.

OBJECTIF: Les délais d'attente pour accéder à la radiothérapie sont longs dans note contexte. L'objet de cette étude était d'analyser le résultat de la chimiothérapie néo adjuvante à la radiothérapie dans les cancers localement avancés du col utérin. PATIENTS ET MÉTHODES: Nous avons réalisé une étude rétrospective allant d'avril 2014 à avril 2016 au centre de radiothérapie de l'hôpital du Mali. Les patients ont été regroupés selon l'âge, le type histologique, la taille de la tumeur, la classification de la FIGO 2002. Le schéma thérapeutique était une chimiothérapie néo adjuvante associant Paclitaxel 175 mg/m2 et Carboplatine AUC 5 toutes les 3 semaines suivie d'une radiothérapie avec linac 6 MV à la dose de 70 Gy en raison de 5 séances de 2 Gy par semaine faite concomitamment à une chimiothérapie avec du cisplatine à la dose de 40 mg/m2/semaine. La réponse clinique était évaluée à la fin de la chimiothérapie néoadjuvante et de la radiochimiothérapie concomitante. RÉSULTATS: Trente patientes ont été incluses dans l'étude. L'âge moyen était de 53.63 ± 8.9 ans. La taille moyenne de la tumeur était de 5,17 cm (2 à 7 cm). Selon la classification FIGO 2002, 10 (33%) étaient en stade IIB distal, 17 (57%) étaient en stade IIIB et 3 (10%) en stade IVA. L'évaluation clinique à la fin de la chimiothérapie néo adjuvante avait retrouvé 17 % de réponses complètes (n=5), 10% de réponses partielles (n=3) 73 % d'évolutions stables (n=22). L'évaluation à la fin de la radiochimiothérapie concomitante avait trouvé une réponse complète chez 27 patientes (90%) et une maladie stable chez 3 (10%). CONCLUSION: La chimiothérapie néo adjuvante à la chimioradiothérapie concomitante dans les cancers localement avancés du col utérin permet la stabilisation de la tumeur et améliore le control local. En raison des délais d'attente longs pour accéder à la radiothérapie, la chimiothérapie néo adjuvante est une alternative pour stabiliser la maladie et réduire le risque de métastases à distance des cancers du col utérin localement avancés.

What to expect from immediate salvage hysterectomy following concomitant chemoradiation and image-guided adaptive brachytherapy in locally advanced cervical cancer.

PURPOSE: Concomitant chemoradiation followed by brachytherapy is the standard treatment for locally advanced cervical cancers. The place of adjuvant hysterectomy remains unclear but tends to be limited to incomplete responses to radiotherapy or local relapse. The aim was to analyse the benefit from immediate salvage surgery following radiation therapy in incomplete responders. METHODS: Among the patients with locally advanced cervical cancer treated with concomitant chemoradiation followed by 3D image-guided adaptive brachytherapy and hysterectomy, cases with genuine macroscopic remnant, defined as at least 1cm in width, were identified. Their clinical data and outcomes were retrospectively reviewed and compared to the patients treated with the same modalities. RESULTS: Fifty-eight patients were included, with a median follow-up of 4.2 years. After hysterectomy, 9 patients had macroscopic residual disease, 10 microscopic and the remaining 39 patients were considered in complete histological response. The 4-year overall survival and disease-free survival rates were significantly decreased in patients with macroscopic residual disease: 50 and 51% versus 92% and 93%, respectively. Intestinal grades 3-4 toxicities were reported in 10.4% and urinary grades 3-4 in 8.6% in the whole population without distinctive histological features. Planning aims were reached in only one patient with macroscopic residuum (11.1%). In univariate analysis, overall treatment time (>55 days) and histological subtype (adenocarcinomas or adenosquamous carcinomas) appeared to be significant predictive factors for macroscopic remnant after treatment completion (P=0.021 and P=0.017, respectively). In multivariate analysis, treatment time was the only independent factor (P=0.046, odds ratio=7.0). CONCLUSIONS: Although immediate salvage hysterectomy in incomplete responders provided a 4-year disease-free survival of 51%, its impact on late morbidity is significant. Efforts should focus on respect of treatment time and dose escalation. Adenocarcinoma might require higher high-risk clinical target volume planning aims.

[Concomitant chemoradiotherapy for muscle-invasive bladder cancer: current knowledge, controversies and future directions]. / Chimioradiothérapie concomitante des tumeurs infiltrantes de la vessie : acquis, controverses et perspectives.

Radical cystectomy with lymphadenectomy is currently the standard of care for muscle-invasive urothelial bladder cancer; however and because of its morbidity and its impact on quality of life, there is a growing tendency for bladder-sparing strategies. Initially reserved for elderly or unfit patients unable to undergo radical cystectomy, chemoradiotherapy became a true alternative to surgery for highly selected patients. Although there are no randomized trials comparing radical cystectomy with bladder preserving approaches, surgery remains the preferred treatment for many clinicians. Furthermore, comparison is even more difficult as modalities of radiotherapy are not consensual and differ between centers with a variability of protocols, volume of irradiation and type of chemotherapy. Several ongoing trials are attempting to optimize chemoradiotherapy and limit its toxicity, especially through techniques of adaptive radiotherapy or targeted therapies.