Operational classification of cutaneous squamous cell carcinomas based on unsupervised clustering of real cases by experts.

BACKGROUND: There is currently no staging system for cutaneous squamous cell carcinoma (cSCC) that is adapted to decision-making and universally used. Experts have unconscious ability to simplify the heterogeneity of clinical situations into a few relevant groups to drive their therapeutic decisions. Therefore, we have used unsupervised clustering of real cases by experts to generate an operational classification of cSCCs, an approach that was successful for basal cell carcinomas. OBJECTIVE: To generate a consensual and operational classification of cSCCs. METHOD: Unsupervised independent clustering of 248 cases of cSCCs considered difficult-to-treat. Eighteen international experts from different specialties classified these cases into what they considered homogeneous clusters useful for management, each with freedom regarding clustering criteria. Convergences and divergences between clustering were analysed using a similarity matrix, the K-mean approach and the average silhouette method. Mathematical modelling was used to look for the best consensual clustering. The operability of the derived classification was validated on 23 new practitioners. RESULTS: Despite the high heterogeneity of the clinical cases, a mathematical consensus was observed. It was best represented by a partition into five clusters, which appeared a posteriori to describe different clinical scenarios. Applicability of this classification was shown by a good concordance (94%) in the allocation of cases between the new practitioners and the 18 experts. An additional group of easy-to-treat cSCC was included, resulting in a six-group final classification: easy-to-treat/complex to treat due to tumour and/or patient characteristics/multiple/locally advanced/regional disease/visceral metastases. CONCLUSION: Given the methodology based on the convergence of unguided intuitive clustering of cases by experts, this new classification is relevant for clinical practice. It does not compete with staging systems, but they may complement each other, whether the objective is to select the best therapeutic approach in tumour boards or to design homogeneous groups for trials.

Guidelines for the diagnosis and treatment of cutaneous squamous cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Cutaneous squamous cell carcinoma (CSCC) accounts for ∼20%-25% of all skin tumors. Its precise incidence is often challenging to determine due to limited statistics and its incorporation with mucosal forms. While most cases have a favorable prognosis, challenges arise in patients presenting with locally advanced or metastatic forms, mainly appearing in immunocompromised patients, solid organ transplantation recipients, or those facing social difficulties. Traditionally, chemotherapy and targeted therapy were the mainstays for advanced cases, but recent approvals of immunotherapeutic agents like cemiplimab and pembrolizumab have revolutionized treatment options. These guidelines, developed by the Italian Association of Medical Oncologists (AIOM) using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, aim to guide clinicians in diagnosing, treating, and monitoring patients with CSCC, covering key aspects from primitive tumors to advanced stages, selected by a panel of experts selected by AIOM and other national scientific societies. The incorporation of these guidelines into clinical practice is expected to enhance patient care and address the evolving landscape of CSCC management.

How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group.

PURPOSE: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. METHODS: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. RESULTS: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. CONCLUSIONS: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology.

De novo metastatic head and neck squamous cell carcinoma: Why does locoregional control "always" matter?

De novo metastatic Head and Neck Squamous Cell Carcinoma (HNSCC) constitutes 10% of recurrent/metastatic (RM) cases. Radiotherapy (RT) has a crucial role in the treatment of locally advanced HNSCC, however its application on RM diseases is still limited. The advent of immune checkpoint inhibitors (ICIs) improves the survival of RM HNSCC, however median overall survival is still limited. Integration of locoregional RT with ICIs in de novo metastatic HNSCC represents a promising treatment option. This perspective aims to explore the role of the combination of locoregional and systemic treatment in improving outcomes for synchronous de novo metastatic HNSCC patients and highlights the principal crucial point in decision making.

Guidelines for the diagnosis and treatment of basal cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.

Linguistic and content validation of the translated and culturally adapted patient-generated subjective global assessment (PG-SGA).

The Patient-Generated Subjective Global Assessment (PG-SGA) is an instrument to screen, assess and monitor malnutrition and risk factors, and to triage for interventions. After having translated and culturally adapted the original PG-SGA for the Italian setting, according to International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Principles, we tested linguistic validity, i.e., perceived comprehensibility and difficulty, and content validity (relevance) of the Italian version of the PG-SGA in patients with cancer and a multidisciplinary sample of healthcare professionals (HCPs). METHODS: After the translation and cultural adaptation of the original PG-SGA for the Italian setting, the patient component (i.e., PG-SGA Short Form (SF) was tested for linguistic validity (i.e., comprehensibility ad difficulty) in 120 Italian patients with cancer and 81 Italian HCPs. The full PG-SGA, i.e., patient and professional component of the PG-SGA, was tested for content validity, i.e., relevance, in 81 Italian HCPs. The data were collected by a questionnaire and evaluations were operationalized by a 4-point scale. Through item and scale indices we evaluated the comprehensibility (I-CI, S-CI), difficulty (I-DI, S-DI) and content validity (I-CVI, S-CVI). Scale indices 0.80-0.89 were considered acceptable, and scale indices ≥0.90 were considered excellent. RESULTS: Patients perceived comprehensibility and difficulty of the PG-SGA SF (Boxes) as excellent (S-CI = 0.98, S-DI = 0.96). Professionals perceived comprehensibility of the professional component (Worksheets) as excellent (S-CI = 0.92), difficulty as acceptable (S-DI = 0.85), and content validity of the full PG-SGA as excellent (S-CVI = 0.92). Dietitians gave higher scores (indicating better scores) on comprehensibility, difficulty, and content validity of Worksheet 4 (physical exam) than the other professions. In Worksheet 4, four items were considered most difficult to complete and were considered below acceptable range. Relevance was perceived as excellent by professionals for both the patient component (S-CVI = 0.93) and the professional component (S-CVI = 0.90), resulting in S-CVI = 0.92 for the full PG-SGA. Slight textual modifications were implemented resulting in the final version of the Italian PG-SGA. CONCLUSIONS: Translation and cultural adaptation of the original PG-SGA resulted in the Italian version of the PG-SGA that maintained its original purpose and meaning and can be completed adequately and easily by patients and professionals. The Italian PG-SGA is considered relevant for screening, assessing and monitoring malnutrition and risk factors, as well as triaging for interventions by Italian HCPs.

Transformation of Cancer Care during and after the COVID Pandemic, a point of no return. The Experience of Italy.

Policymakers everywhere struggle to introduce therapeutic innovation while controlling costs, a particular challenge for the universal Italian National Healthcare System (SSN), which spends only 8.8% of GDP to care for one of the world's oldest populations. Oncology provides a telling example, where innovation has dramatically improved care and survival, transforming cancer into a chronic condition. However, innovation has also increased therapy duration, adverse event management, and service demand. The SSN risks collapse unless centralized cancer planning changes gear, particularly with Covid-19 causing treatment delays, worsening patient prognosis and straining capacity. In view of the 750 billion Euro "Next Generation EU", released by the European Union to relieve Member States hit by the pandemic, the SSN tapped a multidisciplinary research team to identify key strategies for equitable uptake of innovations in treatment and delivery, with emphasis on data-driven technological and managerial advancements - and lessons from Covid-19.

Preventive action with a population of excavator drivers exposed to whole-body vibration.

BACKGROUND: Whole-body vibration is a major cause of lower back pain among employees, and the medical and preventive care teams of occupational health departments are often confronted with lower back pain problems among machine operators. OBJECTIVES: The objectives of this research are to determine the number of excavator drivers exposed to whole-body vibration levels above 0.5m/s2, identify other exposure factors that may contribute to back pain, and propose corrective measures. METHODS: Vibration measurements were carried out on individual excavator drivers while they were observed carrying out working tasks, after which prevention advice is given. Factors which determine vibration levels are logged on to a database. RESULTS: The multivariate analysis of several determining factors shows vibration exposure levels vary depending on the varied work tasks being carried out. CONCLUSION: This study identifies exposed employees among excavator operators. For each workstation, the determining factors that could explain the high exposures to vibrations are identified. This work shows the important role of tasks on exposure levels. A better adaptation of the tools used to carry out work tasks would allow a decrease in the vibration level of this type of machine.

New models of care and multidimensional solutions for oncological patients in the post-acute SARS-COV-2 period: a "Second Phase" also for cancer patients.

In Italy, SARS-CoV-2 outbreak registered a high transmission and disease rates. During the acute phase, oncologists provided to re-organize services and prioritize treatments, in order to limit viral spread and to protect cancer patients. The progressive reduction of the number of infections has prompted Italian government to gradually loosen the national confinement measures and to start the "Second phase" of measures to contain the pandemic. The issue on how to organize cancer care during this post-acute SARS-CoV-2 phase appears crucial and a reassessment of healthcare services is needed requiring new models of care for oncological patients. In order to address major challenges in cancer setting during post-acute SARS-CoV-2 phase, this work offers multidimensional solutions aimed to provide a new way to take care of cancer patients.

Pretreatment DWI with Histogram Analysis of the ADC in Predicting the Outcome of Advanced Oropharyngeal Cancer with Known Human Papillomavirus Status Treated with Chemoradiation.

BACKGROUND AND PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in the period from the 1970s to 2004, due to increase of infection with human papilloma virus (HPV). This study aimed to examine the role of histogram analysis of the ADC in treatment response and survival prediction of patients with oropharyngeal squamous cell carcinoma and known human papillomavirus status. MATERIALS AND METHODS: This was a retrospective single-center study. Following inclusion and exclusion criteria, data for 59 patients affected by T2-T4 (according to the 8th edition of the AJCC Cancer Staging Manual) oropharyngeal squamous cell carcinoma were retrieved. Twenty-eight had human papillomavirus-positive oropharyngeal squamous cell carcinoma, while 31 had human papillomavirus-negative oropharyngeal squamous cell carcinoma. All patients underwent a pretreatment MR imaging. Histogram analysis of ADC maps obtained by DWI (b = 0-1000 mm/s2) was performed on the central section of all of tumors. The minimum follow-up period was 2 years. Histogram ADC parameters were associated with progression-free survival and overall survival. Univariable and multivariable Cox models were applied to the data; P values were corrected using the Benjamini-Hochberg method. RESULTS: At univariable analysis, both human papillomavirus status and mean ADC were associated with progression-free survival (hazard ratio = 0.267, P < .05, and hazard ratio = 1.0028, P ≤ .05, respectively), while only human papillomavirus status was associated with overall survival (hazard ratio = 0.213, P ≤ .05) before correction. At multivariable analysis, no parameter was included (in fact, human papillomavirus status lost significance after correction). If we separated the patients into 2 subgroups according to human papillomavirus status, ADC entropy was associated with overall survival in the human papillomavirus-negative group (hazard ratio = 4.846, P = .01). CONCLUSIONS: ADC and human papillomavirus status are related to progression-free survival in patients treated with chemoradiation for advanced oropharyngeal squamous cell carcinoma; however, this association seems to result from the strong association between ADC and human papillomavirus status.

Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action.

PURPOSE: Despite advances in personalizing the efficacy of cancer therapy, our ability to identify patients at risk of severe treatment side effects and provide individualized supportive care is limited. This is particularly the case for mucositis (oral and gastrointestinal), with no comprehensive risk evaluation strategies to identify high-risk patients. We, the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Mucositis Study Group, therefore aimed to systematically review current evidence on that factors that influence mucositis risk to provide a foundation upon which future risk prediction studies can be based. METHODS: We identified 11,018 papers from PubMed and Web of Science, with 197 records extracted for full review and 113 meeting final eligibility criteria. Data were then synthesized into tables to highlight the level of evidence for each risk predictor. RESULTS: The strongest level of evidence supported dosimetric parameters as key predictors of mucositis risk. Genetic variants in drug-metabolizing pathways, immune signaling, and cell injury/repair mechanisms were also identified to impact mucositis risk. Factors relating to the individual were variably linked to mucositis outcomes, although female sex and smoking status showed some association with mucositis risk. CONCLUSION: Mucositis risk reflects the complex interplay between the host, tumor microenvironment, and treatment specifications, yet the large majority of studies rely on hypothesis-driven, single-candidate approaches. For significant advances in the provision of personalized supportive care, coordinated research efforts with robust multiplexed approaches are strongly advised.

Digital health for optimal supportive care in oncology: benefits, limits, and future perspectives.

BACKGROUND: Digital health provides solutions that capture patient-reported outcomes (PROs) and allows symptom monitoring and patient management. Digital therapeutics is the provision to patients of evidence-based therapeutic interventions through software applications aimed at prevention, monitoring, management, and treatment of symptoms and diseases or for treatment optimization. The digital health solutions collecting PROs address many unmet needs, including access to care and reassurance, increase in adherence and treatment efficacy, and decrease in hospitalizations. With current developments in oncology including increased availability of oral drugs and reduced availability of healthcare professionals, these solutions offer an innovative approach to optimize healthcare resource utilization. DESIGN: This scoping review clarifies the role and impact of the digital health solutions in oncology supportive care, with a view of the current segmentation according to their technical features (connection to sensors, PRO collection, remote monitoring, self-management in real time…), and identifies evidence from clinical studies published about their benefits and limitations and drivers and barriers to adoption. A qualitative summary is presented. RESULTS: Sixty-six studies were identified and included in the qualitative synthesis. Studies supported the use of 38 digital health solutions collecting ePROs and allowing remote monitoring, with benefits to patients regarding symptom reporting and management, reduction in symptom distress, decrease in unplanned hospitalizations and related costs and improved quality of life and survival. Among those 38 solutions 21 provided patient self-management with impactful symptom support, improvement of QoL, usefulness and reassurance. Principal challenges are in developing and implementing digital solutions to suit most patients, while ensuring patient compliance and adaptability for use in different healthcare systems and living environments. CONCLUSIONS: There is growing evidence that digital health collecting ePROs provide benefits to patients related to clinical and health economic endpoints. These digital solutions can be integrated into routine supportive care in oncology practice to provide improved patient-centered care.

Difficulties in conducting pure academic research, obstacles in data collection and quality of informations: The example of the INTERCEPTOR study.

PURPOSE/OBJECTIVE: On September 2009: We started a randomized multicenter phase III study comparing chemoradiation (CRT) (Aldestein RTOG regimen) versus induction chemotherapy followed by Cetuximab radiation (IBRT). The main study's aim was comparison of overall survival but no formal analyses have been made between the two arms because of low accrual and high amount of missing data. The goal of this paper is to identify the reasons of difference in accrual and quality of data among participating centers. MATERIAL/METHODS: Statistic: We correlated data collection quality with relevance of the centers, accrual and number of scientific papers (both specific on HNC and other topics) of each PI. We created an HNC publishing score dividing the number of HNC specific papers for the overall number of published papers. RESULTS: We observed a strong difference in the accrual of pts as well as in the quality of data among the participating centers. The accrual was independent from the quality of data since some centers with low accrual produced high quality data with an excellent follow up. We found a correlation among both number of published papers of each PI and HNC publishing score with the quality of data. CONCLUSION: The study demonstrated that expertise in HNC is important not only to ensure a better outcomes but also to provide high quality data in phase III trials.

Cetuximab in the management of nasopharyngeal carcinoma - a narrative review.

BACKGROUND: Concurrent chemotherapy with radiotherapy is the standard treatment for locoregionally advanced nasopharyngeal cancer. Cetuximab can be used in the treatment of head and neck squamous cell carcinoma. However, the randomised studies that led to approval for its use in this setting excluded nasopharyngeal cancer. In the context of limited data for the use of cetuximab in nasopharyngeal cancer in the medical literature, this review aimed to summarise the current evidence for its use in both primary and recurrent or metastatic disease. METHOD: A literature search was performed using the keywords 'nasopharyngeal neoplasm', 'cetuximab' and 'Erbitux'. RESULTS: Twenty studies were included. There were no randomised phase III trials, but there were nine phase II trials. The use of cetuximab in the treatment of nasopharyngeal carcinoma has been tested in various settings, including in combination with induction chemotherapy and concurrent chemoradiotherapy, and in the palliative setting. CONCLUSION: There is no evidence of benefit from the addition of cetuximab to standard management protocols, and there is some evidence of increased toxicity. There is more promise for its use in metastatic or locally recurrent settings. This review draws together the existing evidence and could provide a focus for future studies.

The pathogenesis of mucositis: updated perspectives and emerging targets.

Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.