Confounding factors in the assessment of oral mucositis in head and neck cancer

Treatment of locally advanced head and neck carcinoma not amenable for surgical resection or resected with high-risk features is usually based on (chemo-)radiation treatment. Oral mucositis represents one of the main side effects of (chemo-)radiation, with an important impact on quality of life and causing approximately 20% of early interruption of treatment, leading to a suboptimal dose administered. Treatment and prevention of oral mucositis have a central role in the therapeutic pathways of head and neck cancer patients but remains quite challenging. Although extensive research is conducted to identify interventions for the management of mucositis, very few interventions had sufficient evidence to generate an international expert consensus. This may be partially explained by confounding factors that could influence the development and assessment of oral mucositis. Little is known about the confounding factors of oral mucositis, which, if not well balanced in an experimental study, could lead to non-solid results. The current paper aims to review the main oral mucositis confounding factors related to head and neck cancer patients

Reply to Caccialanza et al.

International audienceA double-blind phase III trial of immunomodulating nutritional formula during adjuvant chemoradiotherapy in head and neck cancer patients: IMPATOX. Boisselier P, Kaminsky MC, Thézenas S, Gallocher O, Lavau-Denes S, Garcia-Ramirez M, Alfonsi M, Cupissol D, de Forges H, Janiszewski C, Geoffrois L, Sire C, Senesse P; Head and Neck Oncology and Radiotherapy Group (GORTEC). Am J Clin Nutr. 2020 Dec 10;112(6):1523-1531. doi: 10.1093/ajcn/nqaa227. PMID: 32936874 Clinical Trial. Immunonutrition in head and neck cancer patients undergoing chemoradiotherapy: an alternative approach for overcoming potential bias. Caccialanza R, Cereda E, Orlandi E, Filippi AR, Comoli P, Alberti A, Imarisio I, Pedrazzoli P, Bossi P. Am J Clin Nutr. 2021 Apr 6;113(4):1053-1054. doi: 10.1093/ajcn/nqaa421. PMID: 33822867 No abstract available

New Challenges in Evaluating Outcomes after Immunotherapy in Recurrent and/or Metastatic Head and Neck Squamous Cell Carcinoma

In many recurrent and/or metastatic cancers, the advent of immunotherapy opens up new scenarios of treatment response, with new phenomena, such as pseudoprogression and hyperprogression. Because of this, different immune-related response criteria have been developed, and new therapeutic strategies adopted, such as treatment beyond progression. Moreover, the role of progression-free survival as a surrogate has been questioned, and new surrogate endpoint hypotheses have arisen. A proper understanding of radiological imaging, an assessment of the biological events triggered by therapy, and the clinical evolution of the lesions and of the patient performance status are all factors that should be considered to guide the oncologist's treatment choice. The primary aim of this article is to discuss how all these concepts apply to recurrent/metastatic head and neck squamous cell carcinoma patients when treated with immunotherapy

Strategies for clinical development of monoclonal antibodies beyond first-in-human trials: tested doses and rationale for dose selection

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Arsenic and other trace elements in groundwaters and surface waters in the gold mining region of the Nigerien Liptako (Southwestern Niger)

International audienceThe Nigerien Liptako in southwest Niger has gold mineralisations in Birimian formations (Paleoproterozoic) that have been mined for several decades. The objective of this study was to document the concentrations of arsenic and other toxic trace elements in groundwaters, river waters, suspended particulate matter and sediments and discuss the potential influence of artisanal gold mining on arsenic and trace elements enrichment. For this, forty-three groundwater samples (boreholes and wells) were analysed in mined and unmined areas. Surface waters, suspended particulate matters and sediments were sampled in three rivers at stations upstream and downstream from mining sites. Rock samples extracted from mine galleries were collected for mineralogical and geochemical characterization. In groundwater, arsenic concentrations ranged from 0.018 to 202 µg/L, exceeding drinking water guidelines (10 µg/L) in three artisanal gold mining areas. Manganese exhibited concentrations exceeding the potability limit in 23% of the samples, mainly in the Continental Terminal aquifer. In rivers, arsenic was the element most enriched in suspended particulate matter and sediments, but its concentration in water did not exceed 3 µg/L. Mineralogical analysis of rocks showed traces of arsenic in association with iron oxides, suggesting a release of arsenic in groundwater by desorption. The consumption of these waters rich in arsenic or manganese presents serious risks for health. These data represent the first large-scale investigation of arsenic and trace elements concentrations in groundwaters and surface waters in the Nigerien Liptako, where no or very scarce water quality measurements have been published yet

Efficacy thresholds for clinical trials with advanced or metastatic leiomyosarcoma patients

Background: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft-tissue sarcomas. An update is provided for leiomyosarcoma (LMS). Materials and methods: Clinical trials with advanced or metastatic LMS were identified via literature review in PubMed (published 2003–2018, ≥10 adult LMS patients). End-points were 3- and 6-month progression-free survival rates (PFSR-3m and PFSR-6m). When estimates could not be derived from publications, data requests were sent out. Treatments were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guidelines. A random effects meta-analysis was used to pool trial-specific estimates for first-line (1L) or pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale was used to guide the treatment effect to target in future trials. Results: From 47 studies identified, we obtained information on 7 1L and 16 2L+ trials for 1500 LMS patients. Overall, in 1L, PFSR-3m and PFSR-6m were 74% (95% confidence interval [CI] 64–82%) and 58% (95% CI 50–66%), respectively. For 2L+, PFSR-3m was 48% (95% CI 41–54%), and PFSR-6m was 28% (95% CI 22–34%). No difference was observed between R-T and NR-T for first or later lines. Under the alternative that the true benefit amounts to a hazard ratio of 0.65, a PFSR-6m ≥70% can be considered to suggest drug activity in 1L. For 2L+, a PFSR-3m ≥62% or PFSR-6m ≥44% would suggest drug activity. Specific results are also provided for uterine LMS. Conclusions: This work provides a new benchmark for designing phase II studies for advanced or metastatic LMS.</p

New benchmarks to design clinical trials with advanced or metastatic liposarcoma or synovial sarcoma patients: An EORTC – Soft Tissue and Bone Sarcoma Group (STBSG) meta-analysis based on a literature review for soft-tissue sarcomas

Background : Recently, we performed a meta-analysis based on a literature review for STS trials (published 2003–2018, ≥10 adult patients) to update long-standing reference values for leiomyosarcomas. This work is extended for liposarcomas (LPS) and synovial sarcomas (SS). Materials and methods : Study endpoints were progression-free survival rates (PFSRs) at 3 and 6 months. Trial-specific estimates were pooled per treatment line (first-line or pre-treated) with random effects meta-analyses. The choice of the therapeutic benefit to target in future trials was guided by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Results : Information was acquired for 1030 LPS patients (25 trials; 7 first-line, 17 pre-treated, 1 both) and 348 SS patients (13 trials; 3 first-line, 10 pre-treated). For LPS, the overall pooled first-line PFSRs were 69% (95%-CI 60–77%) and 56% (95%-CI 45–67%) at 3 and 6 months, respectively. These rates were 49% (95%-CI 40–57%)/28% (95%-CI 22–34%) for >1 lines. For SS, first-line PFSRs were 74% (95%-CI 58–86%)/56% (95%-CI 31–78%) at 3 and 6 months, and pre-treated rates were 45% (95%-CI 34–57%)/25% (95%-CI 16–36%). Following ESMO-MCBS guidelines, the minimum values to target are 79% and 69% for first-line LPS (82% and 69% for SS) at 3 and 6 months. For pre-treated LPS, recommended PFSRs at 3 and 6 months suggesting drug activity are 63% and 44% (60% and 41% for SS). Conclusions : New benchmarks are proposed for advanced/metastatic LPS or SS to design future histology-specific phase II trials. More data are needed to provide definitive thresholds for the different LPS subtypes