Purpose: Assess cognitive changes after radiotherapy (RT) in brain and head-and-neck (HN) cancer patients using patient-reported outcome measures (PROMs) and evaluate a dose-effect relationship for brain structures.
Materials And Methods: Primary brain and HN cancer patients treated with RT between 2012-2021 were included. Patient characteristics, clinical parameters, and PROMs at baseline and 1-year follow-up were collected.
Background: Head-and-neck cancer (HNC) can cause oropharyngeal dysphagia (OD). Early identification of OD in newly diagnosed HNC patients is important to better prepare patients for their cancer treatment trajectory. The aim of this study is (1) to assess the prevalence of OD in HNC patients within three weeks before the start of cancer treatment and (2) to investigate which demographic and oncological characteristics may be risk factors associated with the risk of OD at baseline.
View Article and Find Full Text PDFHuman papillomavirus (HPV)‑positive and -negative head and neck squamous cell carcinoma (HNSCC) are often associated with activation of the phosphatidylinositol 3‑kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway due to mutations or amplifications in , loss of or activation of receptor tyrosine kinases. In HPV‑negative tumors, (encoding p16 protein) inactivation or (encoding Cyclin D1 protein) amplification frequently results in sustained cyclin‑dependent kinase (CDK) 4/6 activation. The present study aimed to investigate the efficacy of the CDK4/6 inhibitors (CDKi) palbociclib and ribociclib, and the PI3K/Akt/mTOR pathway inhibitors (PI3Ki) gedatolisib, buparlisib and alpelisib, in suppressing cell viability of HPV‑positive and ‑negative HNSCC cell lines.
View Article and Find Full Text PDFPurpose: To report on quality assurance (QA) and protocol adherence (PA) in a multicentre phase III trial for head and neck cancer, evaluate patterns of protocol deviations and investigate the effect of PA on study outcomes.
Methods: All 221 patients from the ARTFORCE trial (NCT01504815) were included in this study. Pre- and per-treatment QA measures included protocol guidelines, a dummy run, early case reviews and trial meetings.
Purpose: To provide patients with MET-mutated advanced non-small cell lung cancer (METmut aNSCLC) access to crizotinib, further substantiate evidence of its efficacy and safety in this setting, and find potential biomarkers for nonresponse.
Patients And Methods: In the Drug Rediscovery Protocol (NCT0295234), patients with an actionable molecular profile are treated with off-label registered drugs. Both treated and untreated patients with aNSCLC harboring MET exon 14 skipping or other MET mutations received crizotinib 250 mg BID until disease progression or intolerable toxicity.
Glioblastoma (GBM) is the most prevalent central nervous system tumour (CNS). Patients with GBM have a dismal prognosis of 15 months, despite an intensive treatment schedule consisting of surgery, chemoradiation and concurrent chemotherapy. In the last decades, many trials have been performed investigating small molecule inhibitors, which target specific genes involved in tumorigenesis.
View Article and Find Full Text PDFGlioblastoma (GBM) continues to exhibit a discouraging survival rate despite extensive research into new treatments. One factor contributing to its poor prognosis is the tumor's immunosuppressive microenvironment, in which the kynurenine pathway (KP) plays a significant role. This study aimed to explore how KP impacts the survival of newly diagnosed GBM patients.
View Article and Find Full Text PDFBackground And Purpose: This multicenter randomized phase III trial evaluated whether locoregional control of patients with LAHNSCC could be improved by fluorodeoxyglucose-positron emission tomography (FDG-PET)-guided dose-escalation while minimizing the risk of increasing toxicity using a dose-redistribution and scheduled adaptation strategy.
Materials And Methods: Patients with T3-4-N0-3-M0 LAHNSCC were randomly assigned (1:1) to either receive a dose distribution ranging from 64-84 Gy/35 fractions with adaptation at the 10thfraction (rRT) or conventional 70 Gy/35 fractions (cRT). Both arms received concurrent three-cycle 100 mg/mcisplatin.
Purpose: To evaluate the efficacy of pembrolizumab across multiple cancer types harboring different levels of whole-genome sequencing-based tumor mutational load (TML; total of nonsynonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234).
Patients And Methods: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in cohort A: breast cancer cohort harboring a TML of 140 to 290, cohort B: tumor-agnostic cohort harboring a TML of 140 to 290, and cohort C: tumor-agnostic cohort harboring a TML >290. Patients received pembrolizumab 200 mg every 3 weeks.
Objectives: Immune checkpoint inhibitors (ICI) have introduced a new era in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Optimal duration for ICI therapy is still unclear and the long-term outcomes and toxicity in patients responding to these therapies warrant further exploration. This study attempts to identify the clinical and biological determinants of a durable response and evaluate outcomes following ICI treatment discontinuation.
View Article and Find Full Text PDFBackground: The prognosis of malignant primary high-grade brain tumors, predominantly glioblastomas, is poor despite intensive multimodality treatment options. In more than 50% of patients with glioblastomas, potentially targetable mutations are present, including rearrangements, altered splicing, and/or focal amplifications of epidermal growth factor receptor (EGFR) by signaling through the RAF/RAS pathway. We studied whether treatment with the clinically available anti-EGFR monoclonal antibody panitumumab provides clinical benefit for patients with RAF/RAS-wild-type (wt) glioblastomas in the Drug Rediscovery Protocol (DRUP).
View Article and Find Full Text PDFBackground: Head-and-neck cancer (HNC) can give rise to oropharyngeal dysphagia (OD), malnutrition, sarcopenia, and frailty. Early identification of these phenomena in newly diagnosed HNC patients is important to reduce the risk of complications and to improve treatment outcomes. The aim of this study was (1) to determine the prevalence of the risk of OD, malnutrition, sarcopenia, and frailty; and (2) to investigate the relation between these phenomena and patients' age, performance status, and cancer group staging.
View Article and Find Full Text PDFBackground: This study aims to investigate the relationship between cancer cachexia and oropharyngeal dysphagia (OD) in patients with head and neck cancer (HNC) prior to chemoradiotherapy or bioradiotherapy (CRT/BRT).
Methods: A prospective cohort study with patients with HNC undergoing CRT/BRT (2018-2021) was conducted. Body composition and skeletal muscle function were evaluated using bioelectrical impedance analysis, handgrip strength, and the short physical performance battery (SPPB).
Background: Response rates of immune checkpoint inhibitor (ICI) therapy for recurrent and/or metastatic head and neck squamous cell carcinoma (R/M HNSCC) are low.
Patients And Methods: This retrospective multicentre cohort study evaluates the predictive and prognostic value of weight loss and changes in body composition prior and during therapy. Patient, tumor, and treatment characteristics of 98 patients were retrieved, including neutrophil and platelet-lymphocyte-ratio (NLR and PLR).
Purpose: Reduced temporal muscle thickness (TMT) has recently been postulated as a prognostic imaging marker and an objective tool to assess patients frailty in glioblastoma. Our aim is to investigate the correlation of TMT and systemic muscle loss to confirm that TMT is an adequate surrogate marker of sarcopenia in newly diagnosed glioblastoma patients.
Methods: TMT was assessed on preoperative MR-images and skeletal muscle area (SMA) was assessed at the third lumbar vertebra on preoperative abdominal CT-scans.
Objective: As preservation of cognitive functioning increasingly becomes important in the light of ameliorated survival after intracranial tumor treatments, identification of eloquent brain areas would enable optimization of these treatments.
Methods: This cohort study enrolled adult intracranial tumor patients who received neuropsychological assessments pre-irradiation, estimating processing speed, verbal fluency and memory. Anatomical magnetic resonance imaging scans were used for multivariate voxel-wise lesion-symptom predictions of the test scores (corrected for age, gender, educational level, histological subtype, surgery, and tumor volume).
BMC Med Genomics
November 2022
Background: Definitive concomitant cisplatin-based chemoradiotherapy (CRT) is the current gold standard for most patients with advanced stage head and neck squamous cell carcinoma (HNSCC) of the pharynx and larynx. Since previous meta-analysis on CRT outcomes in HNSCC have been reported, advances have been made in radiotherapy techniques and clinical management, while HPV-status has been identified as a strong confounding prognostic factor in oropharyngeal cancer. Here, we present real-world outcome data from a large multicenter cohort of HPV-negative advanced stage HNSCC treated with CRT using contemporary IMRT-based techniques.
View Article and Find Full Text PDFObjective: Around 40% of oncology patients receive inadequate pain treatment. A previous study reported pain interventions for only 70% of patients who reported unacceptable pain at the self-service registration desk. The aim of this study is to gain insight in reasons for the absence of pain intervention among oncology patients who reported unacceptable pain.
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