Prognostic role of pre-treatment magnetic resonance imaging (MRI)-based radiomic analysis in effectively cured head and neck squamous cell carcinoma (HNSCC) patients.

OBJECTIVES: To identify and validate baseline magnetic resonance imaging (b-MRI) radiomic features (RFs) as predictors of disease outcomes in effectively cured head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS AND METHODS: Training set (TS) and validation set (VS) were retrieved from preexisting datasets (HETeCo and BD2Decide trials, respectively). Only patients with both pre- and post-contrast enhancement T1 and T2-weighted b-MRI and at least 2 years of follow-up (FUP) were selected. The combination of the best extracted RFs was used to classify low risk (LR) vs. high risk (HR) of disease recurrence. Sensitivity, specificity, and area under the curve (AUC) of the radiomic model were computed on both TS and VS. Overall survival (OS) and 5-year disease-free survival (DFS) Kaplan-Meier (KM) curves were compared for LR vs. HR. The radiomic-based risk class was used in a multivariate Cox model, including well-established clinical prognostic factors (TNM, sub-site, human papillomavirus [HPV]). RESULTS: In total, 57 patients of TS and 137 of VS were included. Three RFs were selected for the signature. Sensitivity of recurrence risk classifier was 0.82 and 0.77, specificity 0.78 and 0.81, AUC 0.83 and 0.78 for TS and VS, respectively. VS KM curves for LR vs. HR groups significantly differed both for 5-year DFS (p<.0001) and OS (p=.0004). A combined model of RFs plus TNM improved prognostic performance as compared to TNM alone, both for VS 5-year DFS (C-index: 0.76 vs. 0.60) and OS (C-index: 0.74 vs. 0.64). CONCLUSIONS: Radiomics of b-MRI can help to predict recurrence and survival outcomes in HNSCC.

Management of loco-regionally advanced squamous laryngeal cancer in elderly patients.

PURPOSE: To describe the management and outcomes of loco-regionally advanced (stages III-IV) laryngeal cancer (LRALC) in elderly patients. METHODS: Clinical records of 88 LRALC patients treated at our Institution from 2002 to 2017 were retrospectively reviewed. Patients were divided in 2 subgroups: age > 65 years (elderly) and age ≤ 65 years (controls). Survivals were estimated with Kaplan-Meier method and compared with log-rank test, multivariate analysis were performed with Cox proportional hazard methods. RESULTS: Eighty-eight LRALC patients were included: 45 elderly and 43 controls. Median follow-up was 55.3 months. Median age was 66 years (range 41-84) in the overall population, 72 years (range 66-84) in the elderly cohort. The majority (98%) of elderly patients had at least one comorbidity (ACE27 1-3), while ACE27 was 0 in 37% of controls (p = 0.0001). ECOG PS was 0 in 42% of elderly vs 79% of controls (p = 0.0029). Clinical stage (TNM eighth edition) was III in 67%, IVA in 22% and IVB in 11%. Treatment consisted in total laryngectomy (TL) in 55%, chemo-radiation in 29%, exclusive radiotherapy in 9%, and conservative surgery in 7%. In elderly patients 2-year disease-free and overall survivals were 58% and 74%, respectively. Multivariate analysis performed on the overall group of 88 patients showed that age (HR 1.07, p = 0.0006) and TNM (for both 7th and 8th Editions HR 0.27 for stage III vs IV, p = 0.0005) maintained an independent statistical significant association with OS. CONCLUSIONS: In this monocentric cohort, age and TNM confirmed their independent prognostic role in LRALC patients. Organ-preservation is still an unmet need in a significant portion of elderly patients.

Impressive and Prolonged Response with Lenvatinib in a Highly Pretreated Patient with Metastatic Clear Cell Renal Cancer: A Case Report.

Clear cell renal carcinoma (ccRCC) can occur in young people and could be associated with an aggressive behavior. While for the first-line treatment in metastatic disease, there is an agreement to rely on an immunotherapy (IO)-based combination regimen, no standard second-line regimens exist. Generally, tyrosine kinase inhibitors (TKIs) are employed, even in sequence, although no trials have demonstrated yet the best succession. Herein, we present the case of a 39-year-old male, with a very aggressive ccRCC with somatic VHL mutation and distant metastases at diagnosis. He was treated with four different lines of therapies, including TKIs, with progressive multiple tumor deposits. Lenvatinib alone as the fifth line was able to induce a remarkable and prolonged tumor shrinkage with manageable toxicities.

A small bowel adenocarcinoma harboring a DDR2 mutation in a celiac patient.

We present the case of a 62-year-old man with a history of celiac disease and IgA deficiency, following a strict gluten-free diet that was admitted to our hospital for recurrent abdominal pain, fatigue and melena. Esophagogastroduodenoscopy and colonoscopy with biopsies were normal. A video-capsule endoscopy was performed and revealed a sub-stenosing, vegetating, and bleeding lesion in the first jejunal loop. He underwent laparotomic surgery with resection of the involved segment with loco-regional lymphadenectomy. The pathological report described a poorly differentiated adenocarcinoma of the jejunum, stage IIIA (pT3pN1). Analysis of next-generation sequencing (NGS) of DNA on the surgical sample revealed a likely pathogenetic variant in exon 15 of the DDR2 gene (c.2003G > A) and a TP53 non-frame-shift deletion (c.585_602del). Considering the risk of recurrence, he was candidate to 6 months of adjuvant chemotherapy with platinum salt and fluoropyrimidine. Thirty-eight months after the diagnosis, the patient is still disease free and in good clinical condition. This is the first described case of SBA with DDR2 mutation. Considering the limited therapeutic options beyond surgery for SBA, molecular analyses could become promising for the search for potential targetable alterations for treatments with new available drugs.

Adenoid Cystic carcinoma of minor salivary glands (AdCCmSG): a multidisciplinary update.

INTRODUCTION: Adenoid cystic carcinoma of minor salivary glands (AdCCmSG) represents a 'rarity in the rarity,' posing a clinical challenge in lack of standardized, evidence-based recommendations. At present, AdCCmSG management is mostly translated from major salivary gland cancers (MSGCs). Ideally, AdCCmSG diagnostic-therapeutic workup should be discussed and carried out within a multidisciplinary, high-expertise setting, including pathologists, surgeons, radiation oncologists and medical oncologists. AREAS COVERED: The present review provides an overview of epidemiology and pathologic classification. Moreover, the most recent, clinically relevant updates in the treatment of AdCCmSG (Pubmed searches, specific guidelines) are critically discussed, aiming to a better understanding of this rare pathologic entity, potentially optimizing the care process, and offering a starting point for reflection on future therapeutic developments. EXPERT OPINION: The management of rare cancers is often hindered by limited data and clinical trials, lack of evidence-based guidelines, and hardly represented disease heterogeneity, which cannot be successfully tackled with a 'one-size-fits-all' approach. Our goal is to address these potential pitfalls, providing an easy-to-use, updated, multidisciplinary collection of expert opinions concerning AdCCmSG management as of today's clinical practice. We will also cover the most promising future perspectives, based on the potential therapeutic targets highlighted within AdCCmSG's molecular background.

Efficacy and activity of treatments after progression from palbociclib plus endocrine therapy in patients with HR+/HER2- metastatic breast cancer: a prospective, monocentric study.

Background: Breast cancer is the most frequent tumour worldwide, and the HR+/HER2- subtype is the most common. For this tumour type, endocrine therapy (ET) is the mainstay of treatment. The association of ET and CDK4/6 inhibitors (CDK4/6i) represents the gold standard for first-line or second-line therapies. However, the optimal therapeutic strategy after CDK4/6i progression is still a matter of debate, with several randomized clinical trials still ongoing. Patients and methods: This is an observational, prospective, real-world study including women with HR+/HER2- metastatic breast cancer progressing to palbociclib plus ET. Patients received either ET or chemotherapy (CT). The primary objective was the evaluation of efficacy of the different therapeutic strategies after palbociclib in terms of median progression-free survival 2. Secondary objectives were the activity of therapeutic strategies measured with the clinical benefit rate, evaluation of the parameters used for the treatment choice, and progression-free survival 1 related to palbociclib plus ET treatment. Results: Overall, 48 patients (median age 53, range 33-78 years) were included. The median progression-free survival 2 was of 5 months in the overall cohort (95% CI 4-48 months) with a statistically significant difference between the two therapeutic strategies adopted (ET versus CT, 10 months versus 5 months, respectively). Regarding secondary objectives, the clinical benefit rate was 55.2% in the CT cohort and 50% in ET. Moreover, women treated with CT had a greater number of visceral metastases and a shorter median progression-free survival 1 than patients who received ET. Conclusions: ET and CT represent two possible therapeutic alternatives for patients progressing on CDK4/6i plus ET. The choice is based on clinical parameters, with a potential preference for ET.

Vitamin B12 status in hospitalised cancer patients: Prevalence and clinical implications of depletion and hypervitaminosis.

BACKGROUND & AIMS: The prevalence and clinical significance of vitamin B12 alterations in patients with cancer are poorly understood. We aimed to assess the prevalence and risk factors of vitamin B12 depletion or hypervitaminosis in patients with cancer. METHODS: We retrospectively included hospitalised patients with cancer in 2017-2022. Plasma B12 levels were stratified as very low (VL, <200 pg/ml), low (L, 200-299 pg/ml), normal (N, 300-812 pg/ml), or high (H, ≥813 pg/ml). We collected demographic and several clinical data (e.g., comorbidities, nutritional status, ECOG-PS, cancer site and stage). Univariate and multivariate analyses for factors associated to the vitamin B12 status were fitted. RESULTS: 788 patients (F/M ratio 1.05, median age 72 years, [25th, 75th percentiles 62, 78 years]) were included. Vitamin B12 was VL in 14.1%, L in 19.4%, N in 49.4%, and H in 17.1% cases. Vitamin B12 distribution increased significantly as function of ECOG-PS levels. Patients with breast cancer were characterized by the highest median B12 value, while colorectal cancer patients by the lowest. Vitamin B12 was also significantly higher in advanced compared to early-stage patients as well as in those who had liver failure. Multivariate analysis showed that the probability of H vs. VL B12 levels was significantly increased in patients with hypoproteinemia, hypo-prealbuminemia, and ECOG-PS≥2, and decreased in those with colorectal and gastric cancer. CONCLUSION: Vitamin B12 impairment is common in cancer patients. Increased vitamin B12 is associated with an impaired clinical status, while vitamin B12 depletion is more common in early-stage cancer and in elderly patients.

Unlocking the Potential Role of Decellularized Biological Scaffolds as a 3D Radiobiological Model for Low- and High-LET Irradiation.

INTRODUCTION: Decellularized extracellular matrix (ECM) bioscaffolds have emerged as a promising three-dimensional (3D) model, but so far there are no data concerning their use in radiobiological studies. MATERIAL AND METHODS: We seeded two well-known radioresistant cell lines (HMV-II and PANC-1) in decellularized porcine liver-derived scaffolds and irradiated them with both high- (Carbon Ions) and low- (Photons) Linear Energy Transfer (LET) radiation in order to test whether a natural 3D-bioscaffold might be a useful tool for radiobiological research and to achieve an evaluation that could be as near as possible to what happens in vivo. RESULTS: Biological scaffolds provided a favorable 3D environment for cell proliferation and expansion. Cells did not show signs of dedifferentiation and retained their distinct phenotype coherently with their anatomopathological and clinical behaviors. The radiobiological response to high LET was higher for HMV-II and PANC-1 compared to the low LET. In particular, Carbon Ions reduced the melanogenesis in HMV-II and induced more cytopathic effects and the substantial cell deterioration of both cell lines compared to photons. CONCLUSIONS: In addition to offering a suitable 3D model for radiobiological research and an appropriate setting for preclinical oncological analysis, we can attest that bioscaffolds seemed cost-effective due to their ease of use, low maintenance requirements, and lack of complex technology.

Charged particle radiotherapy for thyroid cancer. A systematic review.

The role of external beam radiotherapy (EBRT) in thyroid cancer (TC) remains contentious due to limited data. Retrospective studies suggest adjuvant EBRT benefits high-risk differentiated thyroid cancer (DTC) and limited-stage anaplastic thyroid carcinoma (ATC), enhancing locoregional control and progression-free survival when combined with surgery and chemotherapy. Intensity-modulated radiotherapy (IMRT) and particle therapy (PT), including protons, carbon ions, and Boron Neutron Capture Therapy (BNCT), represent advances in TC treatment. Following PRISMA guidelines, we reviewed 471 studies from January 2002 to January 2024, selecting 14 articles (10 preclinical, 4 clinical). Preclinical research focused on BNCT in ATC mouse models, showing promising local control rates. Clinical studies explored proton, neutron, or photon radiotherapy, reporting favorable outcomes and manageable toxicity. While PT shows promise supported by biological rationale, further research is necessary to clarify its role and potential combination with systemic treatments in TC management.

The first real-world study on the role of carbon ion radiotherapy for oligo-metastatic, persistent, or recurrent (MPR) ovarian/fallopian tube cancer.

Introduction: In the multidisciplinary management of oligometastatic, persistent, or recurrent (MPR) ovarian cancer, radiotherapy (RT) is becoming a more and more worthwhile treatment to potentially improve the chronicity of the disease. Particle beam RT has proved to be effective in several gynecological malignancies, but so far no data are available for ovarian cancer. Material and Methods: This is a real-world, retrospective, bi-institutional, single-arm study aimed to assess the effectiveness and the safety of carbon ion RT (CIRT) in this setting. The co-first endpoints are 1-year and 2-year actuarial local control (LC) rates and the objective response rate (ORR) defined on a "per lesion" basis. The secondary endpoint was toxicity. Actuarial outcomes were evaluated using the Kaplan-Meier method while potential predictors were explored using the Log-rank test. Bi-variable logistic regression was employed in the analysis of factors predicting the complete response on a per-lesion basis. Results: 26 patients accounting for a total of 36 lesions underwent CIRT with a total median dose of 52.8 Gy[RBE] (range: 39-64 Gy[RBE]). Five patients received CIRT for re-irradiation. No concomitant systemic therapies were administered during CIRT. Within 12 months after the treatment, 17 lesions (47 %) achieved complete response while 18 (50 %) obtained a partial response with an ORR of 97 %. The achievement of a complete response is related to the dose per fraction (>4.2 Gy[RBE], p = 0.04) and total dose (>52,8 Gy[RBE], p = 0.05). The 1-year LC was 92 % and the 2-year LC was 83 %, according to the achievement of a CR (p = 0.007) and GTV ≤ 14 cm3 (p = 0.024). No grade > 3 toxicities were recorded both in naïve and re-irradiated patients. PARP-i and anti-VEGF seemed not to exacerbate the risk of severe toxicities. Conclusions: CIRT was effective and safe in MPR ovarian cancers, even in the case of re-irradiation. Largest cohort studies and longer follow-up are needed to confirm these data.

The impact of electronic versus paper-based data capture on data collection logistics and on missing scores in thyroid cancer patients.

PURPOSE: The purpose of this study was to investigate the impact of the type of data capture on the time and help needed for collecting patient-reported outcomes as well as on the proportion of missing scores. METHODS: In a multinational prospective study, thyroid cancer patients from 17 countries completed a validated questionnaire measuring quality of life. Electronic data capture was compared to the paper-based approach using multivariate logistic regression. RESULTS: A total of 437 patients were included, of whom 13% used electronic data capture. The relation between data capture and time needed was modified by the emotional functioning of the patients. Those with clinical impairments in that respect needed more time to complete the questionnaire when they used electronic data capture compared to paper and pencil (ORadj 24.0; p = 0.006). This was not the case when patients had sub-threshold emotional problems (ORadj 1.9; p = 0.48). The odds of having the researcher reading the questions out (instead of the patient doing this themselves) (ORadj 0.1; p = 0.01) and of needing any help (ORadj 0.1; p = 0.01) were lower when electronic data capture was used. The proportion of missing scores was equivalent in both groups (ORadj 0.4, p = 0.42). CONCLUSIONS: The advantages of electronic data capture, such as real-time assessment and fewer data entry errors, may come at the price of more time required for data collection when the patients have mental health problems. As this is not uncommon in thyroid cancer, researchers need to choose the type of data capture wisely for their particular research question.

Radiation Therapy for Gestational Trophoblastic Neoplasia: Forward-Looking Lessons Learnt.

Gestational trophoblastic neoplasia (GTN) includes several rare malignant diseases occurring after pregnancy: invasive moles, choriocarcinoma, placental site trophoblastic tumours, and epithelioid trophoblastic tumours. Multidisciplinary protocols including multi-agent chemotherapy, surgery, and occasionally radiotherapy achieve good outcomes for some high-risk metastatic patients. In this narrative review of the published studies on the topic, we have tried to identify the role of radiotherapy. The available studies are mainly small, old, and retrospective, with incomplete data regarding radiotherapy protocols delivering low doses (which can make this disease appear radioresistant in some cases despite high response rates with palliative doses) to wide fields (whole-brain, whole-liver, etc.), which can increase toxicity. Studies considering modern techniques are needed to overcome these limitations and determine the full potential of radiotherapy beyond its antihemorrhagic and palliative roles.

Corrigendum: Optimizing the use of lenvatinib in combination with pembrolizumab in patients with advanced endometrial carcinoma.

[This corrects the article DOI: 10.3389/fonc.2022.979519.].

Use of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer: a multidisciplinary perspective for daily practice.

Background: Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers. Methods: With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events. Conclusions: It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

An eHealth App (CAPABLE) Providing Symptom Monitoring, Well-Being Interventions, and Educational Material for Patients With Melanoma Treated With Immune Checkpoint Inhibitors: Protocol for an Exploratory Intervention Trial.

BACKGROUND: Since treatment with immune checkpoint inhibitors (ICIs) is becoming standard therapy for patients with high-risk and advanced melanoma, an increasing number of patients experience treatment-related adverse events such as fatigue. Until now, studies have demonstrated the benefits of using eHealth tools to provide either symptom monitoring or interventions to reduce treatment-related symptoms such as fatigue. However, an eHealth tool that facilitates the combination of both symptom monitoring and symptom management in patients with melanoma treated with ICIs is still needed. OBJECTIVE: In this pilot study, we will explore the use of the CAPABLE (Cancer Patients Better Life Experience) app in providing symptom monitoring, education, and well-being interventions on health-related quality of life (HRQoL) outcomes such as fatigue and physical functioning, as well as patients' acceptance and usability of using CAPABLE. METHODS: This prospective, exploratory pilot study will examine changes in fatigue over time in 36 patients with stage III or IV melanoma during treatment with ICI using CAPABLE (a smartphone app and multisensory smartwatch). This cohort will be compared to a prospectively collected cohort of patients with melanoma treated with standard ICI therapy. CAPABLE will be used for a minimum of 3 and a maximum of 6 months. The primary endpoint in this study is the change in fatigue between baseline and 3 and 6 months after the start of treatment. Secondary end points include HRQoL outcomes, usability, and feasibility parameters. RESULTS: Study inclusion started in April 2023 and is currently ongoing. CONCLUSIONS: This pilot study will explore the effect, usability, and feasibility of CAPABLE in patients with melanoma during treatment with ICI. Adding the CAPABLE system to active treatment is hypothesized to decrease fatigue in patients with high-risk and advanced melanoma during treatment with ICIs compared to a control group receiving standard care. The Medical Ethics Committee NedMec (Amsterdam, The Netherlands) granted ethical approval for this study (reference number 22-981/NL81970.000.22). TRIAL REGISTRATION: ClinicalTrials.gov NCT05827289; https://clinicaltrials.gov/study/NCT05827289. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/49252.

International Phase IV Field Study for the Reliability and Validity of the European Organisation for Research and Treatment of Cancer Thyroid Cancer Module EORTC QLQ-THY34.

Purpose: The aim of this study was to validate the new European Organisation for Research and Treatment of Cancer Quality of Life Thyroid Cancer Module (EORTC QLQ-THY34). Methods: We enrolled 437 thyroid cancer patients from 17 countries. One group (n = 303), undergoing treatment or best supportive care, completed the questionnaires at three time points (before therapy [t1], 6 weeks later [t2], and 6 months after t2 [t3]). A second group (survivors ≥2 years after diagnosis, n = 134) completed it at a random baseline time point and a second time 1 week later. We determined internal consistency (using Cronbach's alpha), the scale structure (with confirmatory factor analysis), and discriminant validity (using known-group comparisons). Group 1 data were used to assess responsiveness and group 2 data to determine test-retest reliability using intra-class correlations (ICC). Results: All 34 items fulfilled the criteria to be kept in the questionnaire. Cronbach's alpha was >0.70 in 8 of the 9 multi-item scales. All standardized factor loadings exceeded 0.40, confirming the proposed scale structure. The ICC was >0.70 in all scales expressing good test-retest reliability. Differences in scale scores between patients with different histology were >5 points in all scales. In all but one of the pre-specified scales (Dry Mouth), changes over time were ≥|4| points between at least two time points. Conclusion: The EORTC QLQ-THY34 with its 9 multi-item and 8 single-item scales is a reliable and valid tool to measure quality of life in thyroid cancer patients and can be used in future trials and studies.

The observational clinical registry (cohort design) of the European Reference Network on Rare Adult Solid Cancers: The protocol for the rare head and neck cancers.

INTRODUCTION: Care for head and neck cancers is complex in particular for the rare ones. Knowledge is limited and histological heterogeneity adds complexity to the rarity. There is a wide consensus that to support clinical research on rare cancer, clinical registries should be developed within networks specializing in rare cancers. In the EU, a unique opportunity is provided by the European Reference Networks (ERN). The ERN EURACAN is dedicated to rare adults solid cancers, here we present the protocol of the EURACAN registry on rare head and neck cancers (ClinicalTrials.gov Identifier: NCT05483374). STUDY DESIGN: Registry-based cohort study including only people with rare head and neck cancers. OBJECTIVES: to help describe the natural history of rare head and neck cancers;to evaluate factors that influence prognosis;to assess treatment effectiveness;to measure indicators of quality of care. METHODS: Settings and participants It is an hospital based registry established in hospitals with expertise in head and neck cancers. Only adult patients with epithelial tumours of nasopharynx; nasal cavity and paranasal sinuses; salivary gland cancer in large and small salivary glands; and middle ear will be included in the registry. This registry won't select a sample of patients. Each patient in the facility who meets the above mentioned inclusion criteria will be followed prospectively and longitudinally with follow-up at cancer progression and / or cancer relapse or patient death. It is a secondary use of data which will be collected from the clinical records. The data collected for the registry will not entail further examinations or admissions to the facility and/or additional appointments to those normally provided for the patient follow-up. Variables Data will be collected on patient characteristics (eg. patient demographics, lifestyle, medical history, health status); exposure data (eg. disease, procedures, treatments of interest) and outcomes (e.g. survival, progression, progression-free survival, etc.). In addition, data on potential confounders (e.g. comorbidity; functional status etc.) will be also collected. Statistical methods The data analyses will include descriptive statistics showing patterns of patients' and cancers' variables and indicators describing the quality of care. Multivariable Cox's proportional hazards model and Hazard ratios (HR) for all-cause or cause specific mortality will be used to determine independent predictors of overall survival, recurrence etc. Variables to include in the multivariable regression model will be selected based on the results of univariable analysis. The role of confounding or effect modifiers will be evaluated using stratified analysis or sensitivity analysis. To assess treatment effectiveness, multivariable models with propensity score adjustment and progression-free survival will be performed. Adequate statistical (eg. marginal structural model) methods will be used if time-varying treatments/confounders and confounding by indication (selective prescribing) will be present. RESULTS: The registry initiated recruiting in May 2022. The estimated completion date is December 2030 upon agreement on the achievement of all the registry objectives. As of October 2022, the registry is recruiting. There will be a risk of limited representativeness due to the hospital-based nature of the registry and to the fact that hospital contributing to the registry are expert centres for these rare cancers. Clinical Follow-up could also be an issue but active search of the life status of the patients will be guaranteed.

Thrombotic Events during Lenvatinib Treatment: A Single Institution Experience.

Lenvatinib is the standard treatment for radioiodine-refractory differentiated thyroid cancer (RR-DTC). Thromboembolic (TE) side effects are quite rare (1-3% of treated patients) in clinical trials. Nevertheless, patients with predisposing factors are at a higher risk of developing cardiovascular adverse events. Reduction of lenvatinib starting dose and cardiologic counselling to provide appropriate supportive therapies are usually recommended for high-risk patients. From 2016 to 2022, we analyzed a series of 16 patients who were consecutively treated at our institution. All except one patient received a reduction in their dosage after two cycles of therapy because of toxicities, and four patients (25%) suffered from TE. The observed incidence in our patient sample seemed to be higher than expected. We hypothesized that our patient sample might be at higher risk probably because of the heavy prior loco-regional treatments performed.

Electroporation in Head-and-Neck Cancer: An Innovative Approach with Immunotherapy and Nanotechnology Combination.

Squamous cell carcinoma is the most common malignancy that arises in the head-and-neck district. Traditional treatment could be insufficient in case of recurrent and/or metastatic cancers; for this reason, more selective and enhanced treatments are in evaluation in preclinical and clinical trials to increase in situ concentration of chemotherapy drugs promoting a selectively antineoplastic activity. Among all cancer treatment types (i.e., surgery, chemotherapy, radiotherapy), electroporation (EP) has emerged as a safe, less invasive, and effective approach for cancer treatment. Reversible EP, using an intensive electric stimulus (i.e., 1000 V/cm) applied for a short time (i.e., 100 µs), determines a localized electric field that temporarily permealizes the tumor cell membranes while maintaining high cell viability, promoting cytoplasm cell uptake of antineoplastic agents such as bleomycin and cisplatin (electrochemotherapy), calcium (Ca2+ electroporation), siRNA and plasmid DNA (gene electroporation). The higher intracellular concentration of antineoplastic agents enhances the antineoplastic activity and promotes controlled tumor cell death (apoptosis). As secondary effects, localized EP (i) reduces the capillary blood flow in tumor tissue ("vascular lock"), lowering drug washout, and (ii) stimulates the immune system acting against cancer cells. After years of preclinical development, electrochemotherapy (ECT), in combination with bleomycin or cisplatin, is currently one of the most effective treatments used for cutaneous metastases and primary skin and mucosal cancers that are not amenable to surgery. To reach this clinical evidence, in vitro and in vivo models were preclinically developed for evaluating the efficacy and safety of ECT on different tumor cell lines and animal models to optimize dose and administration routes of drugs, duration, and intensity of the electric field. Improvements in reversible EP efficacy are under evaluation for HNSCC treatment, where the focus is on the development of a combination treatment between EP-enhanced nanotechnology and immunotherapy strategies.

Ovarian Cancer Radiosensitivity: What Have We Understood So Far?

Radiotherapy has been increasingly considered as an active treatment to combine with other approaches (i.e., surgery, chemotherapy, and novel target-based drugs) in ovarian cancers to palliate symptoms and/or to prolong chemotherapy-free intervals. This narrative review aimed to summarize the current knowledge of the radiosensitivity/radioresistance of ovarian cancer which remains the most lethal gynecological cancer worldwide. Indeed, considering the high rate of recurrence in and out of the radiotherapy fields, in the era of patient-tailored oncology, elucidating the mechanisms of radiosensitivity and identifying potential radioresistance biomarkers could be crucial in guiding clinical decision-making.