The role of palliative care in relapsed and metastatic head and neck cancer patients in a single ESMO integrated oncology and palliative care centre.

BACKGROUND: Palliative care (PC) for patients with advanced cancer improves symptom management and quality of life and may promote home deaths. Limited data are available regarding PC in advanced head and neck cancer (HNC) patients. The aim of this study was to describe the type of care and modalities of integration of specialized PC in a population of relapsed and/or metastatic head and neck cancer patients, followed in a single institution over 4 years. METHODS: Between January 2016 and December 2019, data on patients with relapsed and/or metastatic head and neck cancer not suitable for curative treatment diagnosed at the Oncology Institute of Southern Switzerland were reviewed retrospectively. Site, type and lines of treatment, treatment response, referral to specialist palliative care (yes or no), type of symptoms, tracheostomy and/or feeding-tube presence, and site of death were documented. Comparisons were made between patients benefitting from PC integration vs standard care. RESULTS: Eighty-six patients with relapsed/metastatic HNC were identified, 63 (73.3%) of whom were referred to specialized PC. Patients were mainly men (66, 76.7%), with a median age of 69 years (range 44-95). The most common site of tumour was the oropharynx (31, 36%), followed by the larynx (21, 24.4%), oral cavity (19, 22.1%), hypopharynx (14, 16.3%), and unknown primary (1, 1.2%). Forty-four patients (51.2%) were treated with systemic treatment. The median time interval between the diagnosis and palliative care referral was 1.7 months. At the time of our analysis, 69 patients had died (58 in the PC group and 11 in the non-PC group). Fifteen patients (25.9%) in the PC group and 4 (36.4%) in the non-PC group had received aggressive treatment (chemotherapy, tracheostomy and/or feeding tube) in the last month of life, with no significant difference between groups (p = 0.44). There was no difference in the incidence of home death (19.1% PC group vs 9.1% non-PC group, p = 0.67) or presence of caregiver (69.8% PC group vs 78.2% non-PC group, p = 0.58) between groups, while palliative care was associated with more opioid use (90.5% vs 17.4%, p < 0.0001). Patients in the PC group had a shorter survival compared to the non-PC group (5.7 vs 19.9 months, p = 0.0063). CONCLUSIONS: This study shows that patients appear to be at risk of receiving inappropriate invasive treatments close to death and of dying in hospital settings. Further research is needed to investigate how early PC may affect decision-making around treatments and improve HNC patients' holistic wellbeing.

Correlation of KRAS G12C Mutation and High PD-L1 Expression with Clinical Outcome in NSCLC Patients Treated with Anti-PD1 Immunotherapy.

BACKGROUND: Immune checkpoint inhibitors (ICIs) targeting PD-1 or PD-L1 improved the survival of non-small cell lung cancer (NSCLC) patients with PD-L1 expression ≥50% and without alterations in EGFR, ALK, ROS1, RET. However, markers able to predict the efficacy of ICIs, in combination with PD-L1 expression are still lacking. Our aim in this hypothesis-generating pilot study was to evaluate whether the KRAS G12C variant may predict the efficacy of ICIs in advanced NSCLC patients with PD-L1 ≥ 50%. METHODS: Genomic DNA or tissue sections of 44 advanced ICI-treated NSCLC cases with PD-L1 ≥ 50% without EGFR, ALK, ROS1, RET alterations were tested using Next Generation Sequencing, Fluorescence in Situ Hybridization and immunohistochemistry. Statistical analyses were carried out fitting univariate and multivariate time to event models. RESULTS: KRAS G12C mutant patients (N = 11/44) showed a significantly longer progression-free survival (PFS) at univariate and multivariate analyses (p = 0.03). The Kaplan-Meier plot of the PFS time-to-event supports that G12C positive patients have a longer time to progress. PFS improvement was not observed when any KRAS mutations were compared to wild-type cases. CONCLUSIONS: Given the limitations due to the small sample size and exploratory nature of this study, we tentatively conclude the KRAS G12C mutation should be considered in future trials as a predictive marker of prolonged response to first-line ICIs in NSCLC patients overexpressing PD-L1. This finding could be relevant as anti-KRAS G12C therapies enter the therapeutic landscape of NSCLC.

Prostate Cancer and Sleep Disorders: A Systematic Review.

Prostate cancer (PCa) treatment involves multiple strategies depending on the disease's stage. Androgen deprivation therapy (ADT) remains the gold standard for advanced and metastatic stages. Sleep quality has been suggested as being additionally influenced also by local radiotherapy, prostatectomy and androgen-receptor (AR)-targeted agents. We performed a systematic review exploring the landscape of studies published between 1 January 1990 and 31 July 2021, investigating sleep disturbances in PCa patients receiving active treatments, including the influence of hormonal therapy on sleep quality as a factor affecting their quality of life. Out of 45 articles identified, 16 studies were selected, which recruited patients with PCa, undergoing active treatment in either a prospective longitudinal or cross-sectional study. Development of sleep disorders or changes in sleep quality were reported in 14 out of 16 trials included. Only five trials included objective measurements such as actigraphy, mostly at one time point and without a baseline assessment. Limitations to be addressed are the small number of existing trials, lack of randomized trials and heterogeneity of methodologies used. This systematic review outlines the lack of prospective trials investigating sleep disorders, with a rigorous methodology, in homogeneous cohorts of PCa patients. Future trials are needed to clarify the prevalence and impact of this side effect of PCa treatments.

P1245 Polymorphic Variants of HSD3B1 Gene Confer Different Outcome in Specific Subgroups of Patients Infected With SARS-CoV-2.

Introduction: Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the androgen receptor (AR), through ACE2 receptor and TMPRSS2, to enter nasal and upper airways epithelial cells. Genetic analyses revealed that HSD3B1 P1245C polymorphic variant increases dihydrotestosterone production and upregulation of TMPRSS2 with respect to P1245A variant, thus possibly influencing SARS-CoV-2 infection. Our aim was to characterize the HSD3B1 polymorphism status and its potential association with clinical outcomes in hospitalized patients with COVID-19 in Southern Switzerland. Materials and Methods: The cohort included 400 patients hospitalized for COVID-19 during the first wave between February and May 2020 in two different hospitals of Canton Ticino. Genomic DNA was extracted from formalin-fixed paraffin-embedded tissue blocks, and HSD3B1 gene polymorphism was evaluated by Sanger sequencing. Statistical associations were verified using different test. Results: HSD3B1 polymorphic variants were not associated with a single classical factor related to worse clinical prognosis in hospitalized patients with SARS-CoV-2. However, in specific subgroups, HSD3B1 variants played a clinical role: intensive care unit admission was more probable in patients with P1245C diabetes compared with P1245A individuals without this comorbidity and death was more associated with hypertensive P1245A>C cases than patients with P1245A diabetes without hypertension. Discussion: This is the first study showing that HSD3B1 gene status may influence the severity of SARS-CoV-2 infection. If confirmed, our results could lead to the introduction of HSD3B1 gene status analysis in patients infected with SARS-CoV-2 to predict clinical outcome.