A GORTEC survey on low-risk CTV-P2 delineation in head and neck cancers.

An international consensus was established in 2018 to standardise practice using geometric (5 + 5 mm) expansion around GTV-P for definitive radiotherapy of squamous cell carcinomas of the head and neck (HNC). The GORTEC (French HNC Oncology and Radiotherapy Group) conducted a survey to assess the level of agreement about CTV-P2 delineation using a "formalised consensus method". The 32 proposals of the 2018 consensus on CTV-P2 and 6 additional GORTEC proposals were submitted to 13 GORTEC radiation oncologists (RO). Proposals were rated as "suitable" for median scores ≥7, "unsuitable" for scores ≤3.5 or "uncertain." The degree of agreement was high (≥85 %), moderate (75-84 %) or low (<75 %). Suitable proposals were reviewed by 40 other RO for final recommendations. The 2018 proposals were "uncertain" with low degrees of agreement (41.5-69 %), except for T1 tumors, which had 89 % agreement. Five out of 6 GORTEC proposals were "suitable" and one "uncertain." The final recommendation was "suitable and to be retained" by 97.5 % of RO, as follows: To obtain CTV-P2, GORTEC recommends applying a "geo-anatomical" approach. Using the geometric concept, 10 mm-isotropic margins are applied to the GTV, for all locations but the hypopharynx (10 mm antero-posterior, laterally and 15 mm craniocaudally). CTV-P2 is further modified using the anatomical concept (anatomical barriers, dissemination routes) and accounting the benefit/risk balance and proximity of organs at risk. The GORTEC survey derived from the 2018 international CTV-Ps delineation consensus suggests a "geo-anatomical" approach for the delineation of CTV-P2 in HNC

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group

BACKGROUND AND PURPOSE: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results. MATERIALS AND METHODS: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible. Individual patient data were collected and combined using a fixed-effect model. OS was the main endpoint. RESULTS: For the main question, 101 trials (18951 patients, median follow-up of 6.5 years) were analyzed. For both questions, there were 16 new (2767 patients) and 11 updated trials. Around 90% of the patients had stage III or IV disease. Interaction between treatment effect on OS and the timing of CT was significant (p < 0.0001), the benefit being limited to concomitant CT (HR: 0.83, 95%CI [0.79; 0.86]; 5(10)-year absolute benefit of 6.5% (3.6%)). Efficacy decreased as patients age increased (p_trend = 0.03). OS was not increased by the addition of induction (HR = 0.96 [0.90; 1.01]) or adjuvant CT (1.02 [0.92; 1.13]). Efficacy of induction CT decreased with poorer performance status (p_trend = 0.03). For the secondary question, eight trials (1214 patients) confirmed the superiority of concomitant CT on OS (HR = 0.84 [0.74; 0.95], p = 0.005). CONCLUSION: The update of MACH-NC confirms the benefit and superiority of the addition of concomitant CT for non-metastatic head and neck cancer

Protective versus pathogenic anti-CD4 immunity: insights from the study of natural resistance to HIV infection

HIV-1 exposure causes several dramatic unbalances in the immune system homeostasis. Here, we will focus on the paradox whereby CD4 specific autoimmune responses, which are expected to contribute to the catastrophic loss of most part of the T helper lymphocyte subset in infected patients, may display the characteristics of an unconventional protective immunity in individuals naturally resistant to HIV-1 infection. Reference to differences in fine epitope mapping of these two oppositely polarized outcomes will be presented, with particular reference to partially or totally CD4-gp120 complex-specific antibodies. The fine tuning of the anti-self immune response to the HIV-1 receptor may determine whether viral exposure will result in infection or, alternatively, protective immunity