This review attempts to give an update of epidemiological knowledge on head and neck cancers (HNC).
Worldwide, from 1990 to 2017, incidence rates for larynx and nasopharyngeal cancers decreased, ...whereas they increased for oro/hypopharyngeal cancers and lip/oral cavity cancers. They are still markedly higher among men than women. South Asia has the highest HNC incidence rate, followed by Europe, North America, and Australasia.Tobacco and alcohol remain the major risk factors. Rate of cancers attributable to human papillomavirus (HPV) among HNCs is highly depending on world region and tobacco use prevalence. It increases in high-income countries. In the US population, the number of HPV-attributable oropharyngeal cancers now exceeds the number of cervix cancers. HPV vaccination for boys is recommended in an increasing number of countries. Many occupations are associated with an increased HNC risk. Fruits and vegetables intake have a protective effect against HNC.
To decrease HNC incidence, measures to reduce tobacco use and alcohol consumption remain essential. Improvement of HPV vaccination coverage is also a major objective. Reduction of carcinogens at occupation, protection of workers from carcinogen exposures, education for better diet, and easy and affordable access to fruits and vegetables can contribute to incidence decrease.
One of the biggest challenges for network meta‐analysis is inconsistency, which occurs when the direct and indirect evidence conflict. Inconsistency causes problems for the estimation and ...interpretation of treatment effects and treatment contrasts. Krahn and colleagues proposed the net heat approach as a graphical tool for identifying and locating inconsistency within a network of randomized controlled trials. For networks with a treatment loop, the net heat plot displays statistics calculated by temporarily removing each design one at a time, in turn, and assessing the contribution of each remaining design to the inconsistency. The net heat plot takes the form of a matrix which is displayed graphically with coloring indicating the degree of inconsistency in the network. Applied to a network of individual participant data assessing overall survival in 7531 patients with lung cancer, we were surprised to find no evidence of important inconsistency from the net heat approach; this contradicted other approaches for assessing inconsistency such as the Bucher approach, Cochran's Q statistic, node‐splitting, and the inconsistency parameter approach, which all suggested evidence of inconsistency within the network at the 5% level. Further theoretical work shows that the calculations underlying the net heat plot constitute an arbitrary weighting of the direct and indirect evidence which may be misleading. We illustrate this further using a simulation study and a network meta‐analysis of 10 treatments for diabetes. We conclude that the net heat plot does not reliably signal inconsistency or identify designs that cause inconsistency.
Based on the hypothesis of synergistic effect of avelumab with cetuximab and radiotherapy, this new combination is tested in a randomised trial against two well-established standard of care (SOC) in ...locally advanced squamous-cell carcinoma of the head and neck (LA-SCCHN).
This phase III trial comprises two cohorts of patients deemed fit to receive cisplatin (100 mg/m2 Q3W) (cohort 1) or unfit to cisplatin (cohort 2). The SOC was Intensity Modulated Radiation Therapy (IMRT) with cisplatin in cohort 1 (arm A) and with weekly cetuximab in cohort 2 (arm D). In both cohorts, experimental arms (arms B and C) were IMRT with cetuximab and avelumab (10 mg/kg day 7 and every 2 weeks) followed by avelumab every two weeks for 12 months. A safety phase was planned among the first 41 patients in experimental arms by monitoring grade ≥IV adverse events (AEs) with an unacceptable rate of 35%.
Between September 2017 and August 2018, 82 patients with LA-SCCHN were randomised including 41 patients in experimental arms. All patients of experimental arms except one (arm C) received entire radiotherapy as planned. Most common grade ≥III AEs were mucositis, radio-dermatitis, and dysphagia. Grade ≥IV AEs occurred in 5/41 (12%) patients, all in arm C (no grade V). This rate was acceptable according to the hypotheses of the safety phase. In the SOC arms, grade ≥IV AEs occurred in 3/21 patients (14%) in arm A and 2/20 (10%) in arm D. One grade V haemorrhage occurred in arm A.
The avelumab–cetuximab–RT combination was tolerable for patients with LA-SCCHN, and the approval was given for continuing the trial without modification.
NCT02999087.
•The toxicities of combination of avelumab cetuximab and radiotherapy were unknown in head and neck squamous-cell carcinoma.•The results of the safety phase of two-cohort phase III trial (fit or unfit to cisplatin) were reported.•Most common grade ≥III AEs were mucositis, radio-dermatitis and dysphagia.•Grade ≥IV AEs occurred in 5/41 (12%) patients, all in unfit cohort; no grade IV AE occurred.•Approval was given for continuing the trial without modification.
Non-Hodgkin lymphoma is the fourth most common malignancy in children, has an even higher incidence in adolescents, and is primarily represented by only a few histologic subtypes. Dramatic progress ...has been achieved, with survival rates exceeding 80%, in large part because of a better understanding of the biology of the different subtypes and national and international collaborations. Most patients with Burkitt lymphoma and diffuse large B-cell lymphoma are cured with short intensive pulse chemotherapy containing cyclophosphamide, cytarabine, and high-dose methotrexate. The benefit of the addition of rituximab has not been established except in the case of primary mediastinal B-cell lymphoma. Lymphoblastic lymphoma is treated with intensive, semi-continuous, longer leukemia-derived protocols. Relapses in B-cell and lymphoblastic lymphomas are rare and infrequently curable, even with intensive approaches. Event-free survival rates of approximately 75% have been achieved in anaplastic large-cell lymphomas with various regimens that generally include a short intensive B-like regimen. Immunity seems to play an important role in prognosis and needs further exploration to determine its therapeutic application. ALK inhibitor therapeutic approaches are currently under investigation. For all pediatric lymphomas, the intensity of induction/consolidation therapy correlates with acute toxicities, but because of low cumulative doses of anthracyclines and alkylating agents, minimal or no long-term toxicity is expected. Challenges that remain include defining the value of prognostic factors, such as early response on positron emission tomography/computed tomography and minimal disseminated and residual disease, using new biologic technologies to improve risk stratification, and developing innovative therapies, both in the first-line setting and for relapse.
Adolescents (age 15 to 21 years) compared with younger children with mature B-cell non-Hodgkin's lymphoma (NHL) have been historically considered to have an inferior prognosis. We therefore analyzed ...the impact of age and other diagnostic factors on the risk of treatment failure in children and adolescents treated on the French-American-British Mature B-Cell Lymphoma 96 (FAB LMB 96) trial.
Patients were divided by risk: group A (limited), group B (intermediate), and group C (advanced), as previously described. Prognostic factors analyzed for event-free survival (EFS) included age (< 15 v ≥ 15 years), stage (I/II v III/IV), primary site, lactate dehydrogenase (LDH), bone marrow/CNS (BM/CNS) involvement, and histology (diffuse large B-cell lymphoma v mediastinal B-cell lymphoma v Burkitt lymphoma or Burkitt-like lymphoma).
The 3-year EFS for the whole cohort was 88% ± 1%. Age was not associated as a risk factor for increased treatment failure in either univariate analysis (P = .15) or multivariate analysis (P = .58). Increased LDH (≥ 2 × upper limit of normal ULN v < 2 × ULN), primary site, and BM-positive/CNS-positive disease were all independent risk factors associated with a significant increase in treatment failure rate (relative risk, 2.0; P < .001, P < .012, and P < .001, respectively).
LDH level at diagnosis, mediastinal disease, and combined BM-positive/CNS-positive involvement are independent risk factors in children with mature B-cell NHL. Future studies should be developed to identify specific therapeutic strategies (immunotherapy) to overcome these risk factors and to identify the biologic basis associated with these prognostic factors in children with mature B-cell NHL.
Highlights • First systematic review evaluating the risk of HPV-related cancer among spouses of patients with an HPV-driven cancer. • The risk of HPV-related cancers among spouses of patients with ...HPV-driven cancer seems slightly increased. • The available literature is however limited by the reduced number of publications and methodological issues. • Further investigations using methodologically robust designs are warranted.
Adenoid cystic carcinoma (ACC) accounts for 1% of malignant head and neck tumours 1 and 10% of salivary glands malignant tumours. The main objective of our study is to investigate the prognostic ...factors influencing the event-free survival (EFS) of patients with ACC.
A multicentre prospective study was conducted from 2009 to 2018. All 470 patients with ACC whose survival data appear in the REFCOR database were included in the study. The main judgement criterion was EFS. Both a bivariate survival analysis using log-rank test and a multivariate using Cox model were performed using the R software.
Average age was 55 years. Females accounted for 59.4% of the cohort. The body mass index (BMI) was normal in 86% of cases. Tumours were located in minor salivary glands in 60% of cases. T3/T4 stages represented 58%; 89% of patients were cN0. histological grade III was observed on 21% of patients. The EFS and overall 5-year survival rates were 50% and 85%, respectively. After adjustment, the most significant pejorative prognostic factors were age ≥65 years (hazard ratio HR = 1.67), BMI<16.5 (HR = 2.62), and lymph node invasion cN (HR = 2.08).
Age, BMI and N stage are the three main clinical prognostic factors determining EFS identified in this prospective series of patients with ACC. Such findings open new research perspectives on the influence of these components on initial patient care.
•Head and neck adenoid cystic carcinoma occur more frequently in women (sex ratio: 1.5).•Age, body mass index and N stage are the three main clinical prognostic factors influencing event-free survival.•Tumour size, perineural invasion and the presence of histological grade III also have a negative influence on prognosis.
To describe relapsed B-cell lymphoma or leukemia in children/adolescents treated with a "Lymphomes Malins B" regimen and their outcome and to identify prognostic factors for survival, we studied ...relapses in the LMB89, 96 and 2001 studies of the Société Française d'Oncologie Pédiatrique (Société Française des Cancers de l'Enfant). Therapeutic guidelines at relapse were to obtain a second complete remission and to consolidate the remission with high-dose chemotherapy followed by autologous stem-cell transplantation. Between July 1989 and March 2007, 67 patients of 1322 (5%) relapsed: 57 had Burkitt lymphoma and 10 had large-cell histology. Three patients were initially treated in risk group A, 41 in group B and 23 in group C. Thirty-three patients had a relapse in one site (15 in the central nervous system) and 34 at multiple sites. Sixty-five patients received salvage chemotherapy and 33 achieved complete remission. Forty-one patients also received high-dose chemotherapy followed by autologous (n=33) or allogeneic (n=8) transplantation. With a median follow-up of 6.4 years, the 5-year survival rate was 29.9%. Nineteen patients were still alive, all but one (group A) received consolidation treatment. Multivariate analysis showed the following factors to be significantly associated with better survival: relapse at one site (P=0.0006), large-cell histology (P=0.012), initial prognostic group A or B with lactate dehydrogenase level below twice the normal value (P=0.005), and time to relapse more than 6 months (P=0.04).
The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined. Children 21 years old or ...younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia (B-NHL/B-ALL) with higher risk factors (bone marrow BM with or without CNS involvement) were randomized to standard intensity French-American-British/Lymphoma Malignancy B (FAB/LMB) therapy or reduced intensity (reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2, M3, M4). All patients with CNS disease had additional high-dose methotrexate (8 g/m2) plus extra intrathecal therapy. Fifty-one percent had BM involvement, 20% had CNS involvement, and 29% had BM and CNS involvement. One hundred ninety patients were randomized. The probabilities of 4-year event-free survival (EFS) and survival (S) were 79% ± 2.7% and 82% ± 2.6%, respectively. In patients in remission after 3 cycles who were randomized to standard versus reduced-intensity therapy, the 4-year EFS after randomization was 90% ± 3.1% versus 80% ± 4.2% (one-sided P = .064) and S was 93% ± 2.7% versus 83% ± 4.0% (one-sided P = .032). Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide, Oncovin vincristine, prednisone (COP) reduction therapy had a significantly inferior EFS and S (P < .001). Standard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL (B-ALL with or without CNS involvement).
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