Background: Head and neck cancer (HNC) and its multimodal treatment substantially impair speech, swallowing, breathing, appearance, and psychosocial well-being. Patient-reported outcome measures (PROMs) improve symptom monitoring and quality of life in oncology, yet their integration into routine HNC care remains inconsistent. This study assessed patterns of PROM use, perceived value, and barriers to implementation among healthcare professionals (HCPs) involved in HNC care. Methods: A 30-item cross-sectional survey was distributed to HCPs treating HNC patients between June 2024 and April 2025. The questionnaire explored PROM use in clinical practice and trials, perceived relevance across care phases, and implementation barriers. Respondents were classified as non-users, occasional users, or regular users. Data were analyzed descriptively with comparisons between groups. Results: Among 133 respondents, 33.8% were non-users, 29.3% occasional users, and 36.8% regular users of PROMs. Users reported inviting half of patients to complete PROMs, predominantly via paper-based questionnaires (67.8%). PROMs were mainly applied during active treatment and early follow-up to monitor symptoms, overall health, and emotional well-being, and were less frequently used to guide treatment decisions. The EORTC QLQ-C30 and HNC-specific tools were most commonly reported. Compared with users, non-users more often cited lack of time, limited training in interpreting PROM data, insufficient institutional support, resource constraints, and lack of appropriate instruments (all p < 0.05). PROM use in clinical trials was associated with routine use (p < 0.001). Conclusions: Although PROMs are widely valued in HNC care, their integration into clinical decision-making remains limited. Addressing organizational, educational, and digital barriers is essential to support sustainable implementation.

BACKGROUND:The current survey was conducted among head and neck cancer physicians across the globe to understand the patterns of care and practice for de-novo oligo-metastatic (OM) and oligo-recurrent (OR) head and neck cancer (HNC). MATERIAL AND METHODS:An 18-item survey questionnaire was designed and distributed through the member organizations of the Young Investigator Subcommittee of the HNCIG. The responses were presented as a proportion of the total response for a particular survey item. RESULTS:A total of 204 responses were obtained with an overall response rate of 15.6 % (204/1307). The incidence of OM disease was reported to be < 10 % by 81.9 % of respondents with a higher incidence of oligo-recurrent disease (up to 20 %). Performance status and extent of disease are absolute essential factors for decision-making. In suitable patients, the majority of respondents (67.4 %) would like to treat with a combination of systemic and local therapy both to primary and metastatic site. For oligo-recurrent HNC, 63.7 % of respondents would treat with both systemic and metastatic directed therapy (MDT) with 27 % would consider MDT alone. Surgery and stereotactic body radiotherapy (SBRT) remain the choice of MDT for lung and liver metastasis. The majority of the respondents use SBRT in > 50 % of their patients. CONCLUSION:The current approach to de-novo OM and oligo-recurrent HNC varies in this global survey, but a significant proportion of respondents support radical intent treatment in select cases. Multicentre retrospective and prospective studies as well as international consensus statement are essential prerequisites for developing future clinical guidelines.

Rectal cancer is an increasingly prevalent malignancy, with growing interest in organ preservation strategies as an alternative to radical surgery, particularly for tumors of the mid-lower rectum. Radiotherapy plays a central role in these approaches and contact X-ray brachytherapy (CXB or Papillon technique) allows for safe dose escalation directly to the tumor, enhancing local control while minimizing toxicity. This report describes the development and implementation of a refined protocol for Papillon CXB, addressing technical challenges related to patient comfort, applicator placement, and procedural accuracy. By the end of 2024, a total of 129 patients with mid-lower rectal cancer had been treated with Papillon CXB in Swiss centers. In February 2022, a refined protocol was introduced, incorporating procedural sedation (Propofol), the lateral decubitus position, and close collaboration with gastroenterologists to improve tumor visualization and precise applicator placement. This updated approach has been applied to 73 patients, mainly with curative intent and organ preservation goals. Sedation significantly improved patient comfort and reduced movement during applicator insertion. The applicator demonstrated excellent stability, even in anatomically challenging cases. The procedure proved to be straightforward, smoothly integrated into clinical workflows, and well-tolerated by patients, with high satisfaction reported by both patients and the medical team. This Swiss protocol offers a practical and patient-centered refinement of Papillon CXB. By addressing critical technical and clinical challenges, it enhances procedural feasibility and safety, ultimately supporting optimal oncological outcomes and wider adoption in rectal cancer management.

Research suggests that metformin may reduce tumor hypoxia, rendering it a potential radiosensitizer. This study investigated metformin’s effect on hypoxia-associated gene expression in oral cavity squamous cell carcinoma (OCSCC). In this prospective trial, non-diabetic patients with OCSCC scheduled for curative surgery received preoperative metformin for 10 to 14 days. Tumor biopsies were taken before and after metformin treatment. Gene expression profiling was performed using RNASeq, emphasizing on hypoxia-associated signaling pathways. Fifteen patients of 25 enrolled patients completed the study protocol and passed quality checks. No significant difference in gene expression was observed after adjustment for multiple testing. No significant changes were found in the hypoxia-associated hypoxia-inducible factor 1- alpha (HIF1A) pathway or in other signaling pathways associated with metformin reported in the literature. This study does not support the hypothesis that metformin improves tumor hypoxia in OCSCC after 10 to 14 days of treatment.

Rectal cancer typically necessitates a combination of radiotherapy (RT), chemotherapy, and surgery. The associated functional disorders and reduction in quality of life have led to an increasing interest in organ preservation strategies. Response strongly correlates with RT dose, but dose escalation with external beam remains limited even with modern external beam RT techniques because of toxicity of the surrounding tissues. This study reports on the use of Papillon, an endocavitary Radiotherapy device, in the treatment of rectal cancer. The device delivers low energy X-rays, allowing for safe dose escalation and better complete response rate. Between January 2015 and February 2024, 24 rectal cancer patients were treated with the addition of a boost delivered by Papillon to standard RT, with or without chemotherapy, in an upfront organ preservation strategy. After a median follow-up (FU) of 43 months, the organ preservation rate was 96% (23/24), and the local relapse rate was 8% (2/24). None of our patients developed grade 3 or more toxicities. Our results demonstrate that the addition of Papillon contact RT provides a high rate of local remission with sustained long-term organ preservation, offering a promising alternative to traditional surgical approaches in patients with rectal cancer.

IntroductionOver the past years, there has been a growing interest in the role of immunotherapy in locally advanced (LA) and recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). High-quality data from prospective trials are lacking for the elderly subpopulation. This systematic review and meta-analysis aims to review the efficacy and safety of immunotherapy in older patients.MethodsA systematic literature search was conducted. Randomized clinical trials providing outcome data on a subgroup of elderly (>65 years old) were available for meta-analysis. Primary outcomes of interest were OS and PFS for efficacy analysis.ResultsSeven studies were included in the systematic review and four in the efficacy analysis. The pooled analysis of OS and PFS showed a consistent benefit (HR 0.78 and 0.91, respectively).ConclusionsImmunotherapy may be an effective and well-tolerated treatment option in the elderly population, but more prospective and randomized data are needed.Systematic Review RegistrationPROSPERO (CRD42022333891).

Note S1, Figure S1-S4, Table S1-S3

Abstract Background Surgery and radiotherapy are well-established standards of care for unilateral stage 0 and I early-stage glottic cancer (ESGC). Based on comparative studies and meta-analyses, functional and oncological outcomes after both treatment modalities are similar. Historically, radiotherapy (RT) has been performed by irradiation of the whole larynx. However, only the involved vocal cord is being treated with recently introduced hypofractionated concepts that result in 8 to 10-fold smaller target volumes. Retrospective data argues for an improvement in voice quality with non-inferior local control. Based on these findings, single vocal cord irradiation (SVCI) has been implemented as a routine approach in some institutions for ESGC in recent years. However, prospective data directly comparing SVCI with surgery is lacking. The aim of VoiceS is to fill this gap. Methods In this prospective randomized multi-center open-label phase III study with a superiority design, 34 patients with histopathologically confirmed, untreated, unilateral stage 0-I ESGC (unilateral cTis or cT1a) will be randomized to SVCI or transoral CO2-laser microsurgical cordectomy (TLM). Average difference in voice quality, measured by using the voice handicap index (VHI) will be modeled over four time points (6, 12, 18, and 24 months). Primary endpoint of this study will be the patient-reported subjective voice quality between 6 to 24 months after randomization. Secondary endpoints will include perceptual impression of the voice via roughness – breathiness – hoarseness (RBH) assessment at the above-mentioned time points. Additionally, quantitative characteristics of voice, loco-regional tumor control at 2 and 5 years, and treatment toxicity at 2 and 5 years based on CTCAE v.5.0 will be reported. Discussion To our knowledge, VoiceS is the first randomized phase III trial comparing SVCI with TLM. Results of this study may lead to improved decision-making in the treatment of ESGC. Trial registration ClinicalTrials.gov NCT04057209. Registered on 15 August 2019. Cantonal Ethics Committee KEK-BE 2019-01506

Background The management of meningiomas is challenging, and the role of postoperative radiotherapy is not standardized. Methods Radiation oncology experts in Swiss centres were asked to participate in this decision-making analysis on the use of postoperative radiotherapy (RT) for meningiomas. Experts from ten Swiss centres agreed to participate and provided their treatment algorithms. Their input was converted into decision trees based on the objective consensus methodology. The decision trees were used as a basis to identify consensus and discrepancies in clinical routine. Results Several criteria used for decision-making in postoperative RT in meningiomas were identified: histological grading, resection status, recurrence, location of the tumour, zugzwang (therapeutic need to treat and/or severity of symptoms), size, and cell division rate. Postoperative RT is recommended by all experts for WHO grade III tumours as well as for incompletely resected WHO grade II tumours. While most centres do not recommend adjuvant irradiation for WHO grade I meningiomas, some offer this treatment in recurrent situations or routinely for symptomatic tumours in critical locations. The recommendations for postoperative RT for recurrent or incompletely resected WHO grade I and II meningiomas were surprisingly heterogeneous. Conclusions Due to limited evidence on the utility of postoperative RT for meningiomas, treatment strategies vary considerably among clinical experts depending on the clinical setting, even in a small country like Switzerland. Clear majorities were identified for postoperative RT in WHO grade III meningiomas and against RT for hemispheric grade I meningiomas outside critical locations. The limited data and variations in clinical recommendations are in contrast with the high prevalence of meningiomas, especially in elderly individuals.

Abstract Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. Patients and Methods: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. Results: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99] and for higher ADC (HR 0.18; CI, 0.05–0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16–30.8). Conclusions: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome.

BACKGROUND:Stage III N2 non-small cell lung cancer (NSCLC) is a very heterogeneous disease associated with a poor prognosis. A number of therapeutic options are available for patients with Stage III N2 NSCLC, including surgery [with neoadjuvant or adjuvant chemotherapy (CTx)/neoadjuvant chemoradiotherapy (CRT)] or CRT potentially followed by adjuvant immunotherapy. We have no clear evidence demonstrating a significant survival benefit for either of these approaches, the selection between treatments is not always straightforward and can come down to physician and patient preference. The very heterogeneous definition of resectability of N2 disease makes the decision-making process even more complex.METHODS:We evaluated the treatment strategies for preoperatively diagnosed stage III cN2 NSCLC among Swiss thoracic surgeons and radiation oncologists. Treatment strategies were converted into decision trees and analysed for consensus and discrepancies. We analysed factors relevant to decision-making within these recommendations.RESULTS:For resectable "non-bulky" mediastinal lymph node involvement, there was a trend towards surgery. Numerous participants recommend a surgical approach outside existing guidelines as long as the disease was resectable, even in multilevel N2. With increasing extent of mediastinal nodal disease, multimodal treatment based on radiotherapy was more common.CONCLUSIONS:Both, surgery- or radiotherapy-based treatment regimens are feasible options in the management of Stage III N2 NSCLC. The different opinions reflected in the results of this manuscript reinforce the importance of a multidisciplinary setting and the importance of shared decision-making with the patient.

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1 R132H mutations. Patients harbouring IDH1 R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations (“non-R132H IDH1/2 mutations”). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1 R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes ( p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1 R132H mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.

Background The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear. Methods This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0-2. Patients were randomly assigned (1:1:1:1) centrally using a minimisation technique to radiotherapy alone (59.4 Gy in 33 fractions; three-dimensional conformal radiotherapy or intensity-modulated radiotherapy), radiotherapy with concurrent oral temozolomide (75 mg/m(2) per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of 150-200 mg/m(2) temozolomide given on days 1-5), or radiotherapy with both concurrent and adjuvant temozolomide. Patients were stratified by institution, WHO performance status score, age, 1p loss of heterozygosity, the presence of oligodendroglial elements on microscopy, and MGMT promoter methylation status. The primary endpoint was overall survival adjusted by stratification factors at randomisation in the intention-to-treat population. A second interim analysis requested by the independent data monitoring committee was planned when two-thirds of total required events were observed to test superiority or futility of concurrent temozolomide. This study is registered with ClinicalTrials.gov, NCT00626990. Findings Between Dec 4, 2007, and Sept 11, 2015, 751 patients were randomly assigned (189 to radiotherapy alone, 188 to radiotherapy with concurrent temozolomide, 186 to radiotherapy and adjuvant temozolomide, and 188 to radiotherapy with concurrent and adjuvant temozolomide). Median follow-up was 55.7 months (IQR 41.0-77.3). The second interim analysis declared futility of concurrent temozolomide (median overall survival was 66.9 months [95% CI 45.7-82.3] with concurrent temozolomide vs 60.4 months [45.7-71.5] without concurrent temozolomide; hazard ratio [HR] 0.97 [99.1% CI 0.73-1.28], p=0.76). By contrast, adjuvant temozolomide improved overall survival compared with no adjuvant temozolomide (median overall survival 82.3 months [95% CI 67.2-116.6] vs 46.9 months [37.9-56.9]; HR 0.64 [95% CI 0.52-0.79], p<0.0001). The most frequent grade 3 and 4 toxicities were haematological, occurring in no patients in the radiotherapy only group, 16 (9%) of 185 patients in the concurrent temozolomide group, and 55 (15%) of 368 patients in both groups with adjuvant temozolomide. No treatment-related deaths were reported. Interpretation Adjuvant temozolomide chemotherapy, but not concurrent temozolomide chemotherapy, was associated with a survival benefit in patients with 1p/19q non-co-deleted anaplastic glioma. Clinical benefit was dependent on IDH1 and IDH2 mutational status. Copyright (C) 2021 Elsevier Ltd. All rights reserved.

PURPOSE:Our purpose was to evaluate neurocognitive function (NCF) and clinical outcomes after early hippocampal avoidance (HA) prophylactic cranial irradiation (PCI) in limited disease (LD) small cell lung cancer (SCLC). METHODS AND MATERIALS:In a phase 2 trial, patients with LD SCLC received HA-PCI concomitant with the second cycle of chemotherapy and thoracic radiation therapy. All patients underwent objective NCF testing at baseline, 6 weeks, and 6 and 12 months after HA-PCI. NCF tests included Hopkins Verbal Learning Test Revised, Controlled Oral Word Association, and Trail Making Tests A and B. The primary endpoint was NCF decline at 6 months after HA-PCI. We assumed ≤30% of patients with no NCF decline to be unpromising. Secondary endpoints included brain metastases-free survival (BMFS), overall survival (OS), and safety of the concomitant treatment. RESULTS:Among the 44 patients enrolled in the trial, 38 had evaluable NCF assessment at 6 months after HA-PCI. The proportion of evaluable patients showing no NCF decline at 6 and 12 months was 34.2% (90% confidence interval [CI], 21.6-48.8) and 48.5% (95% CI, 30.8-66.5), respectively. Median follow-up was 13.2 months (95% CI, 12.6-14.1). At 12 months, BMFS was 84.2% and OS was 87.7% (95% CI, 73.0-94.7). Four patients died of SCLC, 1 of respiratory failure, 1 of hemorrhage, and 1 for unknown reason. The most frequently reported grade ≥3 acute adverse events were anemia (21.4%), febrile neutropenia (19.1%), and fatigue (14.3%). CONCLUSIONS:The proportion of patients showing no NCF decline 6 and 12 months after early HA-PCI does not appear to be better than, but rather similar to, that observed in patients receiving sequential PCI without HA. Early HA-PCI in LD SCLC is feasible, with observation of promising BMFS and OS in this selected population.

2520 Background: Bevacizumab failed to demonstrate overall survival benefit despite markedly prolonged progression-free survival in glioblastoma patients. Reasons for this divergence may include suboptimal patient selection and delayed diagnosis of progression on MRI scans under bevacizumab. Imaging analyses of retrospective and uncontrolled clinical trial cohorts suggest MRI diffusion mapping as a predictor of benefit from bevacizumab. Moreover, amino acid PET has been proposed by the RANO working group for the differentiation of tumor versus edema or gliosis based on proof-of-principle studies demonstrating earlier detection of progression with PET compared to MRI. Methods: ARTE (NCT01443676) was a 2:1 randomized, multi-center, open-label trial of hypofractionated radiotherapy in combination with intravenous bevacizumab every 2 weeks (BEV/RT) versus RT alone in patients with newly diagnosed glioblastoma aged 65 years or older. Patients with histologically and molecularly confirmed IDH wildtype glioblastoma aged 65 years or older were analyzed. MRI was available from 67 and serial 18 FET PET from 30 patients in this post hoc analysis. 18 FET PET intensity ratios and herein reported MRI parameters including tumor volumetric analyses and ADC were analyzed blinded for outcome and study arm. Results: Demographic, clinical and molecular parameters were balanced between treatment arms. Overall survival benefit from bevacizumab was observed for larger contrast-enhancing tumor volumes (hazard ratio [HR] per cm 3 0.94, 95% CI 0.89-0.99, p = 0.032) and higher ADC (HR 0.18, 95% CI 0.05-0.66, p = 0.025) on pre-treatment MRI. Response in the BEV/RT arm by the standard MRI-based RANO criteria was associated with overall survival by trend (HR 0.56, 95% CI 0.30-1.10, time-dependent p = 0.094). In a multivariate model controlling for established risk factors, 18 FET tumor-to-brain uptake ratios (TBR) of non-contrast-enhancing tumor portions predicted inferior overall survival specifically in the BEV/RT arm (HR [per 0.1 18 FET TBR] 1.50, 95% CI 1.05-2.13, time-dependent p = 0.025). Controlling for 18 FET TBR at first follow-up identified benefit from BEV/RT by trend (HR 0.41, 95% CI 0.16-1.07, p = 0.069). Conclusions: Large contrast-enhancing tumor mass and high ADC identify patients with overall survival benefit from bevacizumab. Under bevacizumab, non-contrast enhancing tumor portions can be adequately monitored by amino acid PET.

Opinion statement The mainstay treatment of localized non-melanoma skin cancer (NMSC) is surgical excision or Mohs surgery. However, approximately 5% of patients with NMSC harbor high-risk clinicopathologic features for loco-regional recurrence, and distant metastasis. Prognostic factors such as close or positive margins, tumor size ≥ 2 cm, poor tumor differentiation, perineural invasion, depth of invasion, and immunosuppression have all been associated with increased loco-regional recurrence and impaired survival rates. In these patients more aggressive treatments are needed and radiotherapy (RT) is often discussed as adjuvant therapy after surgical resection. Due to the retrospective setting and the heterogeneity of the available studies, indications for adjuvant RT in patients with localized resected NMSC harboring high-risk features remain debated. Studies highlighting the limitations of our current understanding of the independent prognosis of each risk factor are needed to better define the role of adjuvant RT on outcome of localized NMSC and standardize its indications in the clinical setting.

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1 R132H mutations. This high prevalence is important as IDH1 R132H is presumed to be relatively poor at producing D-2-hydroxyglutarate (D-2HG) whereas high concentrations of this oncometabolite are required to inhibit TET2 DNA demethylating enzymes. Indeed, patients harbouring IDH1 R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations (“non-R132H mutations”). This reduced methylation is seen in multiple tumour types and thus appears independent of site of origin. For 1p/19q non-codeleted glioma patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring non-R132H mutated tumours have better outcome (HR 0.41, 95% CI [0.24, 0.71], p=0.0013). Non-R132H mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p<0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H mutated 1p/19q non-codeleted gliomas have a more favourable prognosis than their IDH1 R132H mutated counterpart is clinically relevant and should be taken into account for patient prognostication. Single sentence summary Astrocytoma patients with tumours harbouring IDH mutations other than p.R132H have increased DNA methylation levels and longer survival