e21540 Background: Immune checkpoint inhibitors (ICIs) and targeted therapies have improved outcomes in metastatic melanoma, but resistance remains a major challenge. Only 50% of patients achieve long-term disease control with ICIs, while most develop resistance to BRAF/MEK inhibitors. Cross-resistance to immunotherapy limits further options, including tumor-infiltrating lymphocyte (TIL) therapy. CSPG4, a cell surface molecule overexpressed in melanoma and minimally expressed in normal tissues, has shown promise as a CAR-T therapy target in preclinical models. We investigated whether CSPG4 expression persists in patients with metastatic melanoma following resistance to multiple treatment lines. Methods: We analyzed clinical and biological data from patients with melanoma treated between 2014 and 2024. Primary, metastatic and matched tumour samples (pre- and post-treatment with BRAF/MEK inhibitors and/or ICIs), obtained from Auria Biobank and from the Istituto Oncologico della Svizzera Italiana (IOSI) underwent CSPG4 immunohistochemistry (IHC). Results: Forty-six samples were analyzed, 31 from IOSI and 15 from Auria. All matched samples obtained before and after systemic treatment were CSPG4 positive, with a different intensity of IHC signal and pattern. In gene expression analysis, CSPG4 levels were 1.25-fold higher in metastases compared to primary tumors and 16.18-fold higher compared to normal tissue. CSPG4 was expressed in 83% of the 206 biobank samples, with the highest levels in primary tumors (97%) and skin metastases (94%) and lower levels in lymph node or distant metastases (73%). In 46 paired samples from patients with BRAF-mutated melanoma, CSPG4 expression was maintained after treatment with BRAF/MEK inhibitors, ICIs, or both, regardless of tissue origin or treatment received. Conclusions: CSPG4 expression is conserved in metastatic melanoma cells even after resistance to targeted therapies and ICIs, supporting its potential as a therapeutic target. These findings provide a strong rationale for the clinical development of CSPG4-directed therapies to address treatment resistance in melanoma.

Background: The timing of immune checkpoint inhibitor (ICI) administration may influence clinical outcomes, incidence, and severity of immune-related adverse events (irAEs), but evidence remains limited. Methods: We conducted a retrospective analysis of 41 patients with advanced melanoma treated with combined ipilimumab and nivolumab at the Istituto Oncologico della Svizzera Italiana between 2018 and 2024. Infusions completed before 2:00 p.m. were classified as morning (AM). Patients receiving ≥50% of doses in the morning were assigned to the AM group; the remaining patients comprised the afternoon (PM) group. Results: Twenty-one patients were included in the AM group and twenty in the PM group. Median progression-free survival (PFS) was not reached in the AM group, compared with 7.8 months in the PM group (univariate HR 0.29, 95% CI 0.12-0.70; p = 0.006). Overall survival (OS) was also significantly improved in the AM group (univariate HR 0.25, 95% CI 0.08-0.80; p = 0.019). The overall incidence of irAEs was similar between groups. However, systemic immunosuppression for grade ≥ 2 toxicities was more frequently required in the PM group (80% vs. 52%, p = 0.06). Conclusions: In this retrospective cohort, morning administration of ICIs was associated with improved PFS and OS in patients with advanced melanoma. While irAE incidence was comparable between groups, patients treated in the afternoon more often required systemic immunosuppression.

Background: Sex differences play a significant role in the epidemiology, biology, and outcomes of many cancers, including glioblastoma (GB), the most common and aggressive primary brain tumor. GB is more frequent in males, while females tend to have longer survival, though the underlying reasons for these differences remain poorly understood. Potential contributors include hormonal influences, sex-specific risk factors, and treatment disparities. Understanding these differences is critical for optimizing personalized treatment strategies. Methods: We conducted a retrospective analysis of patients with gliomas from a neuro-oncological database, with a primary focus on GB cases. Variables collected included sex, age, tumor type, molecular biomarker, and treatment modalities. The primary objective was to assess sex-based differences in tumor characteristics and outcomes, while the secondary objective was to identify predictors of time to progression and mortality. Results: The cohort comprised 125 GB, 48 astrocytomas, and 16 oligodendrogliomas, with no significant sex-based differences in age or tumor type distribution. Among GB patients, multifocality was more prevalent in females (14% vs. 8%; p = 0.01); also, EGFR amplification was more frequent in females (25.5% vs. 52.5%; p = 0.007). Males received chemotherapy (80% vs. 63%; p = 0.04) and radiotherapy (84% vs. 67%; p = 0.03) more frequently than females. Survival was positively associated with MGMT methylation (p = 0.002) and negatively associated with TERT mutation (p = 0.01). Multivariable analysis identified TERT mutation as a predictor of increased mortality (HR = 4.1; 95% CI: 1.2–14; p = 0.025), while multifocality predicted both mortality (HR = 2.3; 95% CI: 1.3–3.9; p = 0.003) and reduced time to progression (HR = 3.3; 95% CI: 1.02–10.6; p = 0.04). Conclusions: This study underscores the importance of sex and molecular profiling in GB management, revealing distinct patterns in tumor characteristics and treatment administration between males and females. Our findings advocate for the integration of sex-specific considerations and molecular profiling into clinical decision-making to improve outcomes for GB patients.

Background:The care of patients with brain tumors is a complex task that requires quality standards and quality assurance indicators. In the present study, several quality indicators were evaluated in routine clinical care. Methods:The EORTC Brain Tumor Group (BTG) developed quality indicators from published guidelines and tested them in 19 BTG sites across Europe. Each site extracted data from the files of 20 randomly selected glioblastoma patients diagnosed in 2018. Associations between quality indicators, site characteristics and median overall survival (mOS) were examined. Results:A total of 364 patient files were evaluated at 19 sites. Excellent compliance was observed in the documentation of neuropathology report with isocitrate dehydrogenase (IDH) status (92.0%), O6 -methylguanine DNA methyltransferase promoter methylation (MGMT) status (78.0%), multidisciplinary case discussion (95.3 %), extent of resection (87.1%), and radiotherapy details (96.9%) as well as consent to chemotherapy (75.5%). Performance was not as good for early postoperative MRI (67.2%), psycho-oncological care (40.5%), avoiding antineoplastic therapy in the last weeks of life (63.1%) and early referral to palliative services (23.5%). Timely start of radiotherapy (P = .0153), the presence of a radiotherapy report in the medical record (P = .0077), and patient education on oral chemotherapy (P = .0002) were positively associated with mOS, while early referral to palliative care was associated with shorter mOS (P < .0001). Conclusions:The quality indicators tested in this research project performed with some variability between sites. Significant associations between individual quality indicators and mOS were observed. The proposed quality indicators should be validated prospectively.

We performed a systematic review of phase I trials specifically conducted for patients with head and neck squamous cell carcinoma published between January 1, 2008 and August 31, 2023. PubMed and Cochrane Library databases were searched using a combination of terms: "((head and neck) OR (head & neck)) AND ((cancer*) OR (tumor*) OR (tumour*) OR (neoplasm*) OR (carcinoma*) OR (malignan*)) AND ((phase 1) OR (phase I))"to identify phase I dose-finding trials including a majority of lymphoma patients. Eighty-five trials (H&N patients N = 1714) were included. Among them, 53 trials complying with inclusion/exclusion criteria and were included in the current analysis: 32 (60 %) enrolled only patients with head and neck cancer, while 21 (40 %) included also patients with other solid tumors. The median rate of grade 3-4 adverse events was 41 %. With regards to clinical activity, the median response rate (RR) was 16 %, which is in line with the usually reported rate for phase I trials enrolling unselected populations of patients with solid tumors.

Imaging has a pivotal role in neuro-oncology for the management of primary and secondary brain tumors [...].

Dual modulation of the MAPK pathway with BRAF (e.g., dabrafenib) and MEK (e.g., trametinib) inhibitors has the potential to re-establish radioiodine (RAI) sensitivity in BRAF-mutated RAI-refractory (RAI-R)-differentiated thyroid carcinoma (DTC) cells. Here we showed that (1) double BRAF/MEK inhibition may still reach a significant redifferentiation in patients with a long-history RAI-R DTC and multiple previous treatments; (2) the addition of high RAI activities may obtain a significant structural response in such patients; and (3) a divergence between increasing thyroglobulin and structural response may be a reliable biomarker or redifferentiation. Accordingly, the add-on prescription of high activities of 131I should be considered in RAI-R patients under multikinase inhibitors with stable or responding structural disease and divergent increase of Tg levels.

Introduction: Dermal Regeneration Templates may be used in the reconstruction of large skin defects after cutaneous malignancy excisions. Bowen's disease (BD; squamous cell carcinoma in situ) is a common and persistent condition that can be related to chronic sun damage, and consequently, is usually located on the head and neck area or on the lower limbs. Literature does not provide clear guidelines on the treatment of BD, limiting itself to describing a wide range of different methods that can be used, including surgery, laser therapy or topical options. However, large lesions tend to scar in the post-operative setting and hence are difficult to treat surgically. Presentation of case: In this paper the authors present a case of a male in his 60s, ASA III score, who presented with a history of histopathologically-confirmed squamocellular carcinoma in the neck and supraclavicular region. Due to recurrent carcinomas the patient was treated with an extensive skin excision and a successful reconstruction using a Dermal Regeneration Template. The work has been reported in line with the SCARE criteria. Discussion: The main surgical problem caused by BD is reaching complete oncological resection and, consequently, the need for extensive skin excisions. Conclusion: The use of the skin substitute resulted in a satisfactory functional and aesthetic result, with total clearance and no recurrence observed after 16 months.

BACKGROUND:Melanoma guidelines recommend surgical excision with 10 mm margins for T1 melanomas (invasive melanomas with Breslow thickness ≤1 mm), including those in radial growth phase, which are without metastatic potential; however, such margins may be problematic on head-and-neck. OBJECTIVE:We compared outcomes of wide (10 mm margins) versus narrow (5 mm margins) excisions in patients with radial growth phase T1 melanoma on head-and-neck including face. METHODS:We retrospectively examined 610 consecutive patients excised with wide versus narrow margins, from 2001 to 2018, at six European centres. In all cases, radial growth phase, and clear margins with 5 or 10 mm of clearance, were ascertained histologically. Multivariable models investigated associations of margins and other factors with overall survival and local recurrence. RESULTS:Three hundred and sixteen (51.8%) patients received wide excision, 219 (69.3%) with primary wound closure, 97 (30.7%) with reconstruction; 294 (48.2%) patients received narrow excision, 264 (89.8%) with primary wound closure, 30 (10.2%) with reconstruction (p < 0.001). Median follow-ups were 88 months (wide) and 187 months (narrow) (inter-quartile ranges 43-133 and 79-206, respectively). Ten-year overall survival (95% confidence interval) was 96.7% (94.2%-99.3%) in wide and 98.2% (96.4%-100%) in narrow patients. Ten-year local recurrence incidence was 6.4% (4.1%-10.1%) in wide and 7.8% (5.3%-11.6%) in narrow groups. Lentigo maligna melanoma subtype appeared associated with increased risk of local recurrence in narrow versus wide patients (15.0% vs. 7.5%; p = 0.190). CONCLUSIONS:Narrower excision margins for T1 radial growth phase melanoma are not associated with worse overall survival (hazard ratio 0.97, p = 0.996) or increased local recurrence (subdistribution hazard ratio: 0.87; p = 0.751) compared to wider margins, and may be safely applied to such lesions, although caution may be required in the presence of lentigo maligna melanoma.

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. 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. Eighty-six patients with relapsed/metastatic HNC were identified, 63 (73.3

ObjectivesThe study aimed to explore the attitudes of Swiss healthcare professionals toward the use of social media in adolescent and young adult oncology, and to examine whether the ongoing social restrictions due to COVID-19 might have altered these attitudes.MethodsThis research was a survey study. The subjects were healthcare providers working in pediatric or adult oncology settings in Switzerland. 62 providers completed the survey. We performed descriptive and inferential statistical analyses.ResultsWhile considered useful for various professional aspects (professional life 62.1%, educational purposes 72.7%, networking 83.3%, patient engagement 57.6%, clinical trial recruitment 51.5%), only a small proportion of participants actually used social media for professional reasons weekly (32.8%). Just over half considered themselves skillful in using these platforms (56.1%). Regression analysis revealed that self-assessed skillfulness with social media, the Covid-19 impact on attitudes, and the oncology setting, significantly predicted assessment of the usefulness of social media. Although, in answers to open items, institutional guidelines were deemed crucial to improve social media use, many respondents seemed unaware of their existence (50.8%). Only a minority reported an impact of Covid-19 on their attitudes towards the professional implementation of social media (25.0%).ConclusionThe global health crisis creates important challenges for young patients with cancer and their healthcare providers. In times of social restrictions, social media may be a promising tools to facilitate health information provision, connectivity, and patient care. Virtual mentorship and targeted social media training interventions might be a good way to improve familiarity with using social media and to increase awareness about existing ethical guidelines for their use.

Background: Several studies proposed the use of positron emission tomography (PET) with Prostate Specific Membrane Antigen (PSMA)-targeting radiopharmaceuticals in brain tumors. Our aim is to calculate the diagnostic accuracy of these methods in high-grade gliomas (HGG) with a bivariate meta-analysis. Methods: A comprehensive literature search of studies on the diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in HGG was performed. Original articles evaluating these imaging methods both in the differential diagnosis between HGG and low-grade gliomas (LGG) and in the assessment of suspicious HGG recurrence were included. Pooled sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), and diagnostic odds ratio (DOR) including 95% confidence intervals (95% CI) were calculated. Statistical heterogeneity was also assessed using the I2 test. Results: The meta-analysis of six selected studies (157 patients) provided the following results about PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals in the diagnosis of HGG: sensitivity 98.2% (95% CI: 75.3–99.9%), specificity 91.2% (95% CI: 68.4–98.1%), LR+ 4.5 (95% CI: 2.2–9.3), LR− 0.07 (95% CI: 0.04–0.15), and DOR 70.1 (95% CI: 19.6–250.9). No significant statistical heterogeneity among the included studies was found (I2 = 0%). Conclusions: the quantitative data provided demonstrate the high diagnostic accuracy of PET/CT or PET/MRI with PSMA-targeting radiopharmaceuticals for HGG detection. However, more studies are needed to confirm the promising role of PSMA-targeted PET in this clinical setting.

Background The main objective was to assess whether CT reports of radiologists subspecialized in oncologic imaging respond better to oncological referrals than reports from general radiologists. The secondary objective was to assess differences in ratings between a senior and junior oncologist. Two hundred radiological reports pertaining to oncological patients were retrospectively selected of which 100 each were written by subspecialized radiologists and general radiologists, respectively. The senior and junior oncologists each rated all CT reports using a Likert scale from 1 to 5 (1 = very poor, 5 = excellent) for the following information: anatomical details; interpretation of findings; need for further explanations; appropriateness of conclusions; overall satisfaction. Comparisons between ratings assigned to reports from generalist radiologists and subspecialty radiologists were performed using the Mann–Whitney U test. Agreement between both oncologists was assessed through Gwet's coefficient. Results For all but two of the five items obtained from the senior oncologist, oncologists' ratings were significantly higher for subspecialty radiologists' reports ( p < 0.01); mean values from both oncologists were generally higher for subspecialty reports ( p < 0.001). Agreement between the senior and junior oncologist in the rating of reports from general and subspecialty radiologists was either moderate to substantial (0.5986–0.6788) or substantial to almost perfect (0.6958–0.8358). Conclusions According to a senior and junior oncologist, CT reports performed by subspecialized radiologists in oncologic imaging are clearer, more accurate, and more appropriate in the interpretation and conclusions compared to reports written by general radiologists. Likewise, the overall satisfaction of the oncologist from a subspecialized radiologist report is higher.

PURPOSE:Thin melanomas (T1; ≤ 1 mm) constitute 70% of newly diagnosed cutaneous melanomas. Regional node metastasis determined by sentinel node biopsy (SNB) is an important prognostic factor for T1 melanoma. However, current melanoma guidelines do not provide clear indications on when to perform SNB in T1 disease and stress an individualized approach to SNB that considers all clinicopathologic risk factors. We aimed to identify determinants of sentinel node (SN) status for incorporation into an externally validated nomogram to better select patients with T1 disease for SNB.PATIENTS AND METHODS:The development cohort comprised 3,666 patients with T1 disease consecutively treated at the Istituto Nazionale Tumori (Milan, Italy) between 2001 and 2018; 4,227 patients with T1 disease treated at 13 other European centers over the same period formed the validation cohort. A random forest procedure was applied to the development data set to select characteristics associated with SN status for inclusion in a multiple binary logistic model from which a nomogram was elaborated. Decision curve analyses assessed the clinical utility of the nomogram.RESULTS:Of patients in the development cohort, 1,635 underwent SNB; 108 patients (6.6%) were SN positive. By univariable analysis, age, growth phase, Breslow thickness, ulceration, mitotic rate, regression, and lymphovascular invasion were significantly associated with SN status. The random forest procedure selected 6 variables (not growth phase) for inclusion in the logistic model and nomogram. The nomogram proved well calibrated and had good discriminative ability in both cohorts. Decision curve analyses revealed the superior net benefit of the nomogram compared with each individual variable included in it as well as with variables suggested by current guidelines.CONCLUSION:We propose the nomogram as a decision aid in all patients with T1 melanoma being considered for SNB.

We thank Hindi é1 for his interest in our study, 2 and we are happy to provide the clarifications requested.We agree that our nomogram has not been prospectively tested on unselected patients with thin melanoma.Although prospective testing is desirable, it would not be ethical to use unselected patients with stage T1 melanoma because sentinel node biopsy (SNB) would be overtreatment in most cases.

therapy, local tacalcitol or Acitretinoin for disseminated variants. No data have been reported so far about the link between porokeratosis and exemestane or trastuzumab. As the patient is still receiving the same oncological treatment, persistence of the lesions could be linked with either the immunotherapy or the antihormonal therapy. Porokeratosis is a disorder of keratinization and antibodies targeting the HER-family receptors can cause disorders at this level The possibility that eruptive porokeratosis must be considered as a paraneoplastic phenomenon in our case cannot be completely ruled out. Nevertheless, the long period of time between both conditions, the fact that skin eruption persists although tumor response to the treatment and a time association with the treatment starting supports a drug induced phenomenon in our opinion.

BACKGROUND:Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs.PATIENTS AND METHODS:Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method.RESULTS:Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup.CONCLUSIONS:Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.