The digital readiness of future physicians: nurturing the post-pandemic medical education.

BACKGROUND: The COVID-19 pandemic has accelerated the integration of digital technologies in the healthcare sector. Telemedicine has notably emerged as a significant tool, offering a range of benefits. However, various barriers, such as healthcare professionals' insufficient technological skills and competencies, can hinder its effective implementation. Scholars have examined the readiness of future physicians, with some studies exploring their readiness before or during the COVID-19 crisis. There is, however, a noteable gap in the literature concerning the post-pandemic period. This study aims to identify gaps in current medical education programs by examining two primary aspects: (1) technical readiness (encompassing general and health-related digital competencies) and (2) behavioural readiness, which includes prior experiences and future intentions related to telemedicine education and implementation among medical students and residents. METHODS: A cross-sectional study was conducted using a web-based questionnaire administered to medical students and residents at a major Northern Italian university. The survey responses were analyzed to ascertain whether their distributions varied across demographic variables such as gender and level of education. RESULTS: The most commonly owned technologies were laptops and smartphones, with smartphones perceived as the easiest to use, while desktop computers presented more challenges. Approximately 38% of respondents expressed apprehension about applying digital health information in decision-making processes. There was a significant lack of both personal and academic experience, with only 16% of students and residents having used telemedicine in a university setting. Despite this, 83% of participants expressed a desire for training in telemedicine, and 81% were open to experimenting with it during their academic journey. Moreover, 76% of respondents expressed interest in incorporating telemedicine into their future clinical practice. CONCLUSIONS: This study highlights the need for medical students and residents to receive specific education in digital health and telemedicine. Introducing curricula and courses in this domain is critical to addressing the challenges of digital healthcare.

Leveraging User-Friendly Mobile Medical Devices to Facilitate Early Hospital Discharges in a Pediatric Setting: A Randomized Trial Study Protocol.

BACKGROUND: Mobile technology is increasingly prevalent in healthcare, serving various purposes, including remote health monitoring and patient self-management, which could prove beneficial to early hospital discharges. AIMS: This study investigates the transitional care program experience facilitating early discharges in a pediatric setting through the use of an easy-to-use mobile medical device (TytoCare™, TytoCare Ltd., Natanya, Israel). OUTCOMES: This study aims to assess the effectiveness of telehomecare in achieving complete resolution of diseases without readmission, compare the length of stay between intervention and standard care groups, and gather user and professional experiences. METHODS: A randomized open-label, controlled pilot study enrolled 102 children, randomly assigned to the telehomecare (TELE) group (n = 51, adopting early hospital discharge with continued home monitoring) or the standard-of-care (STAND) group (n = 51). Primary outcomes include complete disease resolution without readmission. Secondary objectives include recording a shorter length of stay in the intervention group. Surveys on user and professional experiences were conducted. A group of 51 children declining telemedicine services (NO-TELE) was also included. RESULTS: In the TELE group, 100% of children achieved complete disease resolution without readmission, with a median duration of stay of 4 days, significantly shorter than the 7 days in the STAND group (p = 0.01). The telemedicine system demonstrated efficient performance and high satisfaction levels. The NO-TELE group showed no significant differences in demographics or digital technology competence. Perceived benefits of telemedicine included time and cost savings, reduced hospital stays, and technology utility and usability. CONCLUSIONS: This study demonstrates that user-friendly mobile medical devices effectively facilitate early hospital discharges in a pediatric setting. These devices serve as a bridge between home and hospital, optimizing care pathways.

A pediatric telecardiology system that facilitates integration between hospital-based services and community-based primary care.

INTRODUCTION: Telecardiology has emerged as a vital field within telemedicine, fostering collaboration between hospital and community medicine. This pilot study introduces an innovative pediatric telecardiology system, comprising a telecardiology system seamlessly integrated with a hospital telemedicine platform. A smooth flow of ECG execution, transmission, and reporting between Primary Care Pediatrician clinics and the hospital was tested as the primary objective. User experience surveys were also considered. METHODS: The study involved three Primary Care Pediatrician clinics, and the enrollment of children took place consecutively from January to July 2023. We integrated a digital electrocardiographic signal acquisition unit and online information transmission-capable tablets, that were provided to the pediatricians, with a telemedicine multitenant platform that facilitated the transmission of the patient's ECG data from the community to the Hospital Pediatric Cardiologist. RESULTS: A total of 158 children (80 M/78F, 8.9 ± 2.8 yrs) underwent ECG recording (78.5 % medical certificates, 21.5 % presence of symptoms) The transmission and reporting of ECGs were successfully completed in all cases, without technical issues. Normal findings on the ECG were demonstrated in 94.9 % of children. 70.8 % of respondents completed all parts of the survey. Respondents had a high level of education (90 %) and demonstrated excellent or good competence in using digital technologies (89 %). 51 % of respondents were not familiar with the term "Telemedicine" and 81 % of the cases had no previous telemedicine experience. 90 % of users were very satisfied or satisfied with the service. Connection problems (2.8 %) and concerns about the service's reliability compared to standard care (3.7 %) were mentioned as possible limitations of the telecardiology. CONCLUSIONS: Our pediatric telecardiology system offers a valuable diagnostic tool to enhance patient management in the community.

Sample size and predictive performance of machine learning methods with survival data: A simulation study.

Prediction models are increasingly developed and used in diagnostic and prognostic studies, where the use of machine learning (ML) methods is becoming more and more popular over traditional regression techniques. For survival outcomes the Cox proportional hazards model is generally used and it has been proven to achieve good prediction performances with few strong covariates. The possibility to improve the model performance by including nonlinearities, covariate interactions and time-varying effects while controlling for overfitting must be carefully considered during the model building phase. On the other hand, ML techniques are able to learn complexities from data at the cost of hyper-parameter tuning and interpretability. One aspect of special interest is the sample size needed for developing a survival prediction model. While there is guidance when using traditional statistical models, the same does not apply when using ML techniques. This work develops a time-to-event simulation framework to evaluate performances of Cox regression compared, among others, to tuned random survival forest, gradient boosting, and neural networks at varying sample sizes. Simulations were based on replications of subjects from publicly available databases, where event times were simulated according to a Cox model with nonlinearities on continuous variables and time-varying effects and on the SEER registry data.

The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients.

Background. The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. Methods. A retrospective (2006−2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV−) and EBV+ nasopharyngeal cancer patients (young: <65 years vs. elderly: ≥65 years) treated with radiotherapy with or without chemotherapy. The impact of age and viral status on overall (OS) and disease-free survival (DFS) were studied with multivariable models, which were adjusted for smoking, stage, comorbidities, chemotherapy dose intensity and treatment strategy. Results. We analyzed 324 patients (146 HPV+ oropharynx, 63 HPV−, 115 nasopharynx). Elderly patients had more comorbidities, and received less intensive treatments when compared to younger subjects. Although OS and DFS were shorter in older patients, after adjustment for stage, smoking, comorbidities, treatment strategy and dose intensity, no significant differences in terms of survival were observed according to age (65 vs. 50 years of age: HR 1.89, 95% CI 0.45−7.84 for HPV+ OPC; HR 0.91, 95% CI 0.29−2.89 for HPV− OPC; HR 1.99, 95% CI 0.9−4.39 for NPC; p = 0.395). Conclusions. Several potential age-related (comorbidities, treatment intensity) and disease-related (stage) confounding factors play a prognostic role with differential impacts on both virus and non-virus-related tumors. In HPV+ oropharyngeal cancer and in EBV+ nasopharyngeal cancer patients, age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor.

Evaluation of the CNC® prosthetic system in recurrent breast cancer patients with chemotherapy-induced alopecia: a pilot study.

BACKGROUND: Chemotherapy-induced alopecia (CIA), although generally reversible, is felt as extremely distressing by patients with breast cancer. A certified medical device (Capelli Naturali a Contatto®-CNC®) was produced to provide patients with a personalized scalp prosthesis, reproducing the patient's original hair, resistant to any type of everyday or sporting activity, and hairdressing. AIMS: The present study aimed to evaluate the impact of the CNC® device on the patient's perception of their body image, psychological wellbeing, satisfaction, strengths and weakness of the CNC® device. METHOD: A pilot study was carried out on 21 patients affected by CIA due to recurrent breast cancer. A mixed quantitative/qualitative method was used, including administering a questionnaire and a focus group. RESULTS: Based on the Body Image Scale, body image perception improved after 3 and 6 months using the device in the 20 patients who answered the questionnaire. No significant change over time emerged for the six dimensions investigated by the Italian version of the Psychological Well-Being Scale. The thematic analysis of the focus groups showed six themes: definition of the prosthetic device, acceptance of the proposal, experience with the conventional wig, strengths, weaknesses, economic issues. CONCLUSION: Compared to the previous experience of CIA and the standard wig, the use of the CNC® device improved everyday life and may be proposed to women undergoing chemotherapy and expecting alopecia to prevent discomfort, social embarrassment, and compromised body image.

Live or Heat-Killed Lactobacillus rhamnosus Aerosolization Decreases Adenomatous Lung Cancer Development in a Mouse Carcinogen-Induced Tumor Model.

An immunosuppressive microenvironment in lung concurs to pre-malignant lesions progression to cancer. Here, we explore if perturbing lung microbiota, which contribute to immunosuppression, by antibiotics or probiotic aerosol interferes with lung cancer development in a mouse carcinogen-induced tumor model. Urethane-injected mice were vancomycin/neomycin (V/N)-aerosolized or live or dead L. rhamnosus GG (L.RGG)-aerosolized, and tumor development was evaluated. Transcriptional profiling of lungs and IHC were performed. Tumor nodules number, diameter and area were reduced by live or heat-killed L.RGG, while only a decrease in nodule diameter was observed in V/N-treated lungs. Both L.RGG and V/N reduced Tregs in the lung. In L.RGG-treated groups, the gene encoding the joining chain (J chain) of immunoglobulins was increased, and higher J chain protein and IgA levels were observed. An increased infiltration of B, NK and myeloid-derived cells was predicted by TIMER 2.0. The Kaplan-Meier plotter revealed an association between high levels of J chain mRNA and good prognosis in lung adenocarcinoma patients that correlated with increased B and CD4 T cells and reduced Tregs and M2 macrophages. This study highlights L.RGG aerosol efficacy in impairing lung cancer growth by promoting local immunity and points to this non-invasive strategy to treat individuals at risk of lung cancer.

Cancer pain: Results of a prospective study on prognostic indicators of pain intensity including pain syndromes assessment.

BACKGROUND: Pain is a prevalent symptom in patients with advanced cancer. Recognition of prognostic factors associated with pain intensity, could help provide better assessment, leading to better pain management. AIM: identifying prognostic factors which could guide improvements on cancer pain classification. DESIGN: a prospective observational study on chronic cancer pain, exploring the association between average mean pain intensity during a 28 days study follow-up and patients' clinical and pain-related characteristics, including pain syndromes. To evaluate these associations, a mixed model was built. SETTING/PARTICIPANTS: Patients attending a Palliative Care and Pain Outpatient Clinic from May 2015 to June 2019 were screened. Patients with moderate to severe cancer pain who were already receiving or needed treatment with third step WHO ladder opioids were enrolled in the study. Data from 342 patients with at least one follow-up visit were analyzed. RESULTS: Pain intensity decreased significantly for all patients during time (p < 0.001). Age, sex, emotional distress, pain duration and neuropathic pain presence evaluated by the Douleur Neuropathique 4 Questions (DN4) questionnaire were not significantly associated to pain intensity. Breakthrough/episodic pain was associated with higher pain intensity during follow-up (p < 0.001). The diagnosis of pain syndrome was overall significantly associated with mean pain intensity during follow-up (p = 0.016). Particularly, the concurrent presence of visceral and soft (p = 0.026) or soft and nervous tissue pain (p = 0.043) were significantly related to worse outcome, whereas pain due to only soft tissue damage with better outcome (p = 0.032). CONCLUSIONS: The recognition of specific pain syndromes may help to better classify cancer pain.

Ibrutinib improves survival compared with chemotherapy in mantle cell lymphoma with central nervous system relapse.

Central nervous system (CNS) relapse of mantle cell lymphoma (MCL) is a rare phenomenon with dismal prognosis, where no standard therapy exists. Since the covalent Bruton tyrosine kinase (BTK) inhibitor ibrutinib is effective in relapsed/refractory MCL and penetrates the blood-brain barrier (BBB), on behalf of Fondazione Italiana Linfomi and European Mantle Cell Lymphoma Network we performed a multicenter retrospective international study to investigate the outcomes of patients treated with ibrutinib or chemoimmunotherapy. In this observational study, we recruited patients with MCL with CNS involvement at relapse who received CNS-directed therapy between 2000 and 2019. The primary objective was to compare the overall survival (OS) of patients treated with ibrutinib or BBB crossing chemotherapy. A propensity score based on a multivariable binary regression model was applied to balance treatment cohorts. Eighty-eight patients were included. The median age at study entry was 65 years (range, 39-87), 76% were males, and the median time from lymphoma diagnosis to CNS relapse was 16 months (range, 1-122). Patients were treated with ibrutinib (n = 29, ibrutinib cohort), BBB crossing chemotherapy (ie, high-dose methotrexate ± cytarabine; n = 29, BBB cohort), or miscellaneous treatments (n = 30, other therapy cohort). Both median OS (16.8 vs 4.4 months; P = .007) and median progression-free survival (PFS) (13.1 vs 3.0 months; P = .009) were superior in the ibrutinib cohort compared with the BBB cohort. Multivariable Cox regression model revealed that ibrutinib therapeutic choice was the strongest independent favorable predictive factor for both OS (hazard ratio [HR], 6.8; 95% confidence interval [CI], 2.2-21.3; P < .001) and PFS (HR, 4.6; 95% CI, 1.7-12.5; P = .002), followed by CNS progression of disease (POD) >24 months from first MCL diagnosis (HR for death, 2.4; 95% CI, 1.1-5.3; P = .026; HR for death or progression, 2.3; 95% CI, 1.1-4.6; P = .023). The addition of intrathecal (IT) chemotherapy to systemic CNS-directed therapy was not associated with superior OS (P = .502) as the morphological variant (classical vs others, P = .118). Ibrutinib was associated with superior survival compared with BBB-penetrating chemotherapy in patients with CNS relapse of MCL and should be considered as a therapeutic option.

Increased acid sphingomyelinase levels in pediatric patients with obesity.

The level of secretory acid sphingomyelinase (S-ASM), a key enzyme in the sphingolipid metabolism, is elevated in a variety of human diseases, including in the serum of obese adults. Alterations in S-ASM were also found to induce morphological changes in erythrocytes. Consequently, the inhibition of S-ASM by functional Inhibitors of ASM (FIASMA) may have broad clinical implications. The purpose of this study was to assess S-ASM activity in pediatric patients with obesity and healthy matched controls, as well as to investigate the erythrocyte morphology using transmission electron microscopy. We recruited 46 obese patients (mean age 11 ± 2.9 years) and 44 controls (mean age 10.8 ± 2.9 years). S-ASM activity was significantly higher (Wilcoxon signed-rank test p-value: 0.004) in obese patients (mean 396.4 ± 49.7 pmol/ml/h) than in controls (mean 373.7 ± 23.1 pmol/ml/h). No evidence of morphological differences in erythrocytes was found between the two populations. We then carried out a case-control study based on the spontaneous reporting system database to compare FIASMAs with NON-FIASMAs in terms of weight gain risk. Children who received FIASMA had a significantly lower frequency of weight gain reports than patients who took NON-FIASMA agents (p < 0.001). Our findings suggest there is an intriguing possibility that S-ASM may play a role in pediatric obesity. This pilot study could serve as the basis for future studies in this interesting field of research.

Managing Care during the COVID-19 Pandemic: The Point of View and Fears of Pediatric Cancer Patients' Families.

(1) Background: When the COVID-19 pandemic arrived, changes had to be made to several management aspects at our Pediatric Oncology Unit. We investigated how the families perceived these changes. (2) Methods: Two questionnaires were developed at the Pediatric Oncology Unit of the Istituto Nazionale dei Tumori in Milan in order to explore how the pandemic had affected the experience of patients who had been or were being treated at our hospital, as well as their families. These questionnaires were administered to three groups of individuals. (3) Results: Between July and October 2020, 120 questionnaires were administered to parents of patients. The impact of school closures and the impossibility of attending sports and social activities outside the hospital were regarded as important, and it was reported that 77.5% of parents judged social distancing to have affected their children. Regarding the changes introduced in the management of the ward and outpatient clinic, most parents' opinions were positive. Differences in the opinions expressed by Groups 2 and 3 were statistically significant on the topics of relationships in the ward and staff workload. The aspect most negatively affected by the pandemic was the support that patients' parents were able to give each other. Regardless of whether patients were treated before the pandemic or after the first lockdown, all parents indicated strong degrees of satisfaction with the care received and the organizational arrangements. (4) Conclusions: The results of our study point us in the right direction to further improve our daily work and better respond to the needs of our patients and their families.

Neoadjuvant chemotherapy in high-risk soft tissue sarcomas: A Sarculator-based risk stratification analysis of the ISG-STS 1001 randomized trial.

BACKGROUND: The value of neoadjuvant chemotherapy in soft tissue sarcoma (STS) is not completely understood. This study investigated the benefit of neoadjuvant chemotherapy according to prognostic stratification based on the Sarculator nomogram for STS. METHODS: This study analyzed data from ISG-STS 1001, a randomized study that tested 3 cycles of neoadjuvant anthracycline plus ifosfamide (AI) or histology-tailored (HT) chemotherapy in adult patients with STS. The 10-year predicted overall survival (pr-OS) was estimated with the Sarculator and was stratified into higher (10-year pr-OS < 60%) and lower risk subgroups (10-year pr-OS ≥ 60%). RESULTS: The median pr-OS was 0.63 (interquartile range [IQR], 0.51-0.72) for the entire study population, 0.62 (IQR, 0.51-0.70) for the AI arm, and 0.64 (IQR, 0.51-0.73) for the HT arm. Three- and 5-year overall survival (OS) were 0.86 (95% confidence interval [CI], 0.82-0.93) and 0.81 (95% CI, 0.71-0.86) in lower risk patients and 0.69 (95% CI, 0.70-0.85) and 0.59 (95% CI, 0.51-0.72) in the higher risk patients (log-rank test, P = .004). In higher risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.68 and 0.58, respectively, and 0.85 and 0.66, respectively, in the AI arm (P = .04); the corresponding figures in the HT arm were 0.69 and 0.60, respectively, and 0.69 and 0.55, respectively (P > .99). In lower risk patients, the 3- and 5-year Sarculator-predicted and study-observed OS rates were 0.85 and 0.80, respectively, and 0.89 and 0.82, respectively, in the AI arm (P = .507); the corresponding figures in the HT arm were 0.87 and 0.81, respectively, and 0.86 and 0.74, respectively (P = .105). CONCLUSIONS: High-risk patients treated with AI performed better than predicted, and this adds to the evidence for the efficacy of neoadjuvant AI in STS. LAY SUMMARY: People affected by soft tissue sarcomas of the extremities and trunk wall are at some risk of developing metastasis after surgery. Preoperative or postoperative chemotherapy has been tested in clinical trials to reduce the chances of distant metastasis. However, study findings have not been conclusive. This study stratified the risk of metastasis for people affected by sarcomas who were included in a clinical trial testing neoadjuvant chemotherapy. Exploiting the prognostic nomogram Sarculator, it found a benefit for chemotherapy when the predicted risk, based on patient and tumor characteristics, was high.

Nomogram to predict the outcomes of patients with microsatellite instability-high metastatic colorectal cancer receiving immune checkpoint inhibitors.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC) is unprecedented. A relevant proportion of subjects achieving durable disease control may be considered potentially 'cured', as opposed to patients experiencing primary ICI refractoriness or short-term clinical benefit. We developed and externally validated a nomogram to estimate the progression-free survival (PFS) and the time-independent event-free probability (EFP) in patients with MSI-high mCRC receiving ICIs. METHODS: The PFS and EFP were estimated using a cure model fitted on a developing set of 163 patients and validated on a set of 146 patients with MSI-high mCRC receiving anti-programmed death (ligand)1 (PD-(L)1) ± anticytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. A total of 23 putative prognostic factors were chosen and then selected using a random survival forest (RSF). The model performance in estimating PFS probability was evaluated by assessing calibration (internally-developing set and externally-validating set) and quantifying the discriminative ability (Harrell C index). RESULTS: RFS selected five variables: ICI type (anti-PD-(L)1 monotherapy vs anti-CTLA-4 combo), ECOG PS (0 vs >0), neutrophil-to-lymphocyte ratio (≤3 vs >3), platelet count, and prior treatment lines. As both in the developing and validation series most PFS events occurred within 12 months, this was chosen as cut-point for PFS prediction. The combination of the selected variables allowed estimation of the 12-month PFS (focused on patients with low chance of being cured) and the EFP (focused on patients likely to be event-free at a certain point of their follow-up). ICI type was significantly associated with disease control, as patients receiving the anti-CTLA-4-combination experienced the best outcomes. The calibration of PFS predictions was good both in the developing and validating sets. The median value of the EFP (46%) allowed segregation of two prognostic groups in both the developing (PFS HR=3.73, 95% CI 2.25 to 6.18; p<0.0001) and validating (PFS HR=1.86, 95% CI 1.07 to 3.23; p=0.0269) sets. CONCLUSIONS: A nomogram based on five easily assessable variables including ICI treatment was built to estimate the outcomes of patients with MSI-high mCRC, with the potential to assist clinicians in their clinical practice. The web-based system 'MSI mCRC Cure' was released.

Aromatase Inhibitors in Postmenopausal Women with Hormone Receptor-Positive Breast Cancer: Profiles of Psychological Symptoms and Quality of Life in Different Patient Clusters.

BACKGROUND: Aromatase inhibitors (AIs) as adjuvant therapy after breast cancer (BC) surgery have demonstrated to reduce the risk of disease recurrence, to lower the risk of contralateral BC, and to improve survival when compared to tamoxifen in patients with limited-stage hormone receptor-positive (HR+) BC. However, AIs are associated with adverse events that can have a significant impact on patient quality of life (QoL). AIM: This study aimed to identify profiles of psychological symptoms and QoL in HR+ BC patients undergoing AI therapy. METHOD: Data were collected with questionnaires administered at three time points: AI initiation (t0); 3 months after AI initiation (t1); and 6 months after AI initiation (t2). The FACT-G, FACT-B, and FACT-ES questionnaires were used to assess QoL; psychological symptoms were assessed using the SCL-90-R. RESULTS: 43 women were enrolled in the study (t0), and 37 completed the t1 evaluation and 29 the t2 evaluation. We found (1) a progressive decrease over time in FACT-G and FACT-ES scores, in particular in the Physical, Emotional, and Endocrine subscales, and an increase in the SOM (somatization) subscale of the SCL-90-R; (2) the presence of 4 clusters related to different psychological symptoms and QoL evolution over time; (3) that patients belonging to the cluster characterized by worsening symptoms and QoL during time differed from the others in the Emotional subscale of the FACT-B and in the GSI (Global Score), OCD (obsessive-compulsive), DEP (depression), ANX (anxiety), and SLP (sleep disorders) dimensions of the SCL-90-R and had significantly higher BMI levels; and (4) that 3 items from the SCL-90-R and 2 items from FACT Emotional Well-Being subscale were predictive of the "worst" cluster. CONCLUSIONS: Although larger studies are needed to confirm these results, our data open up new ways of investigation into the effects of AIs on QoL in HR+ BC patients.

Locally advanced epithelial sinonasal tumors: The impact of multimodal approach.

OBJECTIVE: Outcomes of locally advanced epithelial sinonasal cancers remain unsatisfactory; moreover, only limited and heterogeneous data exist on prognostic factors. METHODS: We reviewed all consecutive patients with American Joint Committee Cancer stage III to IV epithelial sinonasal cancers treated with platinum-based induction chemotherapy (IC) followed by locoregional treatment between 1996 and 2015. RESULTS: We identified 69 patients treated with a multimodal approach (IC, surgery, radiotherapy). Overall, 44 patients recurred (64%). Of those, 19 patients received salvage surgery, but only four remained disease-free. Median overall survival (OS) was 62.5 months. Sinonasal neuroendocrine and small cell histotypes (P = 0.0085), neuroendocrine differentiation (P = 0.006), and lack of response to IC (P = 0.03) were associated with worse OS. In patients who recurred, median OS was 13 months since recurrence. Survival was longer in patients submitted to salvage surgery (44%) than in those receiving chemotherapy alone at recurrence (29.5 vs. 4.6 months). Patients with a clinical benefit after palliative chemotherapy had a longer median OS than those with disease progression (29.2 vs. 4.4 months; P < 0.0001). CONCLUSION: Globally, the prognosis of locally advanced epithelial sinonasal cancers is dismal, with worse outcomes for neuroendocrine lesions. In the recurrent setting, feasibility of salvage surgery and clinical benefit from palliative chemotherapy are associated with longer OS. A multimodal treatment strategy with IC seems to offer improved OS when compared with other retrospective series not employing such a therapeutic tool. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:857-865, 2020.

Long-term outcome of re-irradiation for recurrent or second primary head and neck cancer: A multi-institutional study of AIRO-Head and Neck working group.

BACKGROUND: To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published. METHODS: We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population. RESULTS: Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm3 were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability. CONCLUSION: Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population.

Prevalence of Fatigue in Head and Neck Cancer Survivors.

INTRODUCTION: In head and neck cancer (HNC) patients, fatigue is present throughout the course of treatment and during follow-up. There are limited data about the prevalence and factors associated with fatigue in HNC survivors. The objectives of this study were to assess the prevalence of fatigue and its interference with daily life activities and examine the association between fatigue and gender, age, primary tumour site, Human Papillomavirus (HPV) status, previous oncologic therapy, and time since end of treatment. METHODS: Consecutive locally advanced HNC patients having completed curative treatment at least 1 year earlier and free of disease were asked to fill in the Brief Fatigue Inventory (BFI) questionnaire. Fatigue was categorized according to BFI average score as absent (0), mild (>0 to <4), moderate (≥4 to ≤6), and severe (>6 to ≤10). RESULTS: From February 2015 to July 2016, 129 patients (median age = 60 years old; 67% male) were evaluated. Primary sites of cancer were oropharynx (46%, with 4/5 patients HPV positive), nasopharynx (22%), larynx/hypopharynx (14%), oral cavity (13%), and paranasal sinus or salivary gland (5%). Oncologic treatment was completed 12 to 96 months earlier (median = 34 months). Fatigue was reported as absent in 15% of the patients, mild in 67%, moderate in 11%, and severe in 7%. No association between BFI average score and the analyzed variables was identified. DISCUSSION: Moderate and severe fatigue was reported in 18% of HNC survivors. Further research is needed to assess its causes and improve the management.

Is a pharmacogenomic panel useful to estimate the risk of oxaliplatin-related neurotoxicity in colorectal cancer patients?

Oxaliplatin-induced peripheral neurotoxicity (OXPN) is a dose-limiting toxicity in colorectal cancer (CRC) patients. Single nucleotide polymorphisms (SNPs) in genes involved in drug transport may lead to higher intracellular oxaliplatin accumulation in the dorsal root ganglia and thus increased risk of OXPN. In this study, a panel of 5 SNPs, namely ABCC2 (-24C > T/rs717620 and c.4544 G > A/rs8187710), ABCG2 (c.421 C > A/rs2231142), ABCB1 (c.3435 C > T/rs1045642) and SLC31A1 (c.-36 + 2451 T > G/rs10981694), was evaluated to assess their association with grade 2-3 OXPN in metastatic CRC patients. SNPs were considered according to a dominant model (heterozygous + homozygous). Germline DNA was available from 120 patients who received oxaliplatin between 2010 and 2016. An external cohort of 80 patients was used to validate our results. At the univariable logistic analyses, there were no significant associations between SNPs and incidence of OXPN. Taking into account the strength of observed association between OXPN and the SNPs, a clinical risk score was developed as linear predictor from a multivariable logistic model including all the SNPs together. This score was significantly associated with grade 2-3 OXPN (p = 0.036), but the external calibration was not satisfactory due to relevant discrepancies between the two series. Our data suggest that the concomitant evaluation of multiple SNPs in oxaliplatin transporters is an exploratory strategy that may deserve further investigation for treatment customization in CRC patients.