A Survey on Knowledge and Attitudes Towards Vaccination Against Herpes Zoster Virus Among Medical Oncologists for Patients with Solid Tumors.

Herpes zoster (HZ) virus reactivation is a significant medical problem among immunocompromised patients, especially considering its potential complications. Although the recombinant HZ vaccine has demonstrated > 90% efficacy against HZ in adults, its use is not as frequent as needed in daily oncology practice due to several barriers, including oncologists' knowledge, patients' willingness, and organizational issues. A web-based survey was sent to 139 oncologists treating solid tumors concerning their knowledge and attitudes toward the adjuvanted gE-based recombinant HZ vaccination. The survey included questions regarding the characteristics of medical oncologists participating, such as the type of hospital, main field of expertise, percent of work with patients, awareness of the HZ risk in cancer patients, knowledge of scientific data and scientific societies guidelines on HZ vaccination, familiarity with vaccinations, frequency of HZ detection in clinical practice, barriers, and challenges toward vaccine administration. Fifty-four physicians (46%; 95% CI 0.2918 to 0.5069) responded to all the questions. The main reason for non-response was the lack of time due to the overwhelming burden of assistance. When the survey was launched, 31 participants reported good knowledge of scientific and clinical data of HZ vaccines, 10% none, and 36 were aware of guidelines. Reported barriers included knowledge of the problem, patients' willingness, and organizational issues. Surveying medical oncologists on the adjuvanted gE-based recombinant HZ vaccination provides essential insights into their knowledge, attitudes, and practices regarding vaccination for cancer patients. These data suggest that continuing medical education is necessary to implement HZ vaccination prescription among oncologists.

Immune checkpoint inhibitor therapy­related pneumonitis: How, when and why to diagnose and manage (Review).

Immune checkpoint inhibitor (ICI) therapy has revolutionized cancer treatment by enhancing the immune response against tumor cells. However, their influence on immune pathways can lead to immune-related adverse events such as pneumonitis, necessitating rapid diagnosis and management to prevent severe complications. These adverse events arise from the activation of the immune system by immunotherapeutic drugs, leading to immune-mediated inflammation and tissue damage in various organs and tissues throughout the body. The present review article discusses the pathophysiology, clinical presentation, diagnostic modalities and management strategies for ICI-related pneumonitis, emphasizing early recognition and tailored interventions. Future research endeavors should focus on elucidating the underlying mechanisms of pneumonitis and identifying predictive biomarkers to guide personalized treatment strategies in this evolving field of oncology.

New Frontiers in the Treatment of Patients with HER2+ Cancer and Brain Metastases: Is Radiotherapy Always Useful?

Brain metastases (BM) pose a significant challenge in the management of HER2+ breast cancer since almost 50% of patients with HER2+ breast cancer develop brain tumors. The complex process of brain metastases involves genetic mutations, adaptations and mechanisms to overcome the blood-brain barrier. While radiotherapy is still fundamental in local therapy, its use is associated with cognitive adverse effects and limited long-term control, necessitating the exploration of alternative treatments. Targeted therapies, including tyrosine kinase inhibitors, monoclonal antibodies, and antibody-drug conjugates, offer promising options for HER2+ breast cancer patients with BM. Clinical trials have demonstrated the efficacy of these agents in controlling tumor growth and improving patient outcomes, posing the question of whether radiotherapy is always the unique choice in treating this cancer. Ongoing research into novel anti-HER2 antibodies and innovative combination therapies holds promise for advancing treatment outcomes and enhancing patient care in this clinical scenario. This narrative review provides a comprehensive overview of traditional medical treatments, molecularly targeted therapy and investigational agents in the management of HER2+ breast cancer with BM, highlighting the evolving landscape and potential future directions in treatment strategies to improve patient survival and quality of life.

The Consistency and Quality of ChatGPT Responses Compared to Clinical Guidelines for Ovarian Cancer: A Delphi Approach.

INTRODUCTION: In recent years, generative Artificial Intelligence models, such as ChatGPT, have increasingly been utilized in healthcare. Despite acknowledging the high potential of AI models in terms of quick access to sources and formulating responses to a clinical question, the results obtained using these models still require validation through comparison with established clinical guidelines. This study compares the responses of the AI model to eight clinical questions with the Italian Association of Medical Oncology (AIOM) guidelines for ovarian cancer. MATERIALS AND METHODS: The authors used the Delphi method to evaluate responses from ChatGPT and the AIOM guidelines. An expert panel of healthcare professionals assessed responses based on clarity, consistency, comprehensiveness, usability, and quality using a five-point Likert scale. The GRADE methodology assessed the evidence quality and the recommendations' strength. RESULTS: A survey involving 14 physicians revealed that the AIOM guidelines consistently scored higher averages compared to the AI models, with a statistically significant difference. Post hoc tests showed that AIOM guidelines significantly differed from all AI models, with no significant difference among the AI models. CONCLUSIONS: While AI models can provide rapid responses, they must match established clinical guidelines regarding clarity, consistency, comprehensiveness, usability, and quality. These findings underscore the importance of relying on expert-developed guidelines in clinical decision-making and highlight potential areas for AI model improvement.

Consensus statements and treatment algorithm to guide clinicians in the selection of maintenance therapy for patients with newly diagnosed, advanced ovarian carcinoma: Results of a Delphi study.

INTRODUCTION: Standard treatment of newly diagnosed, advanced ovarian carcinoma (OC) consists of cytoreductive surgery followed by platinum-based chemotherapy with or without bevacizumab. Maintenance therapy with PARP inhibitors and olaparib-bevacizumab has recently shown to significantly improve progression-free survival in the first-line setting. Some practical aspects of maintenance therapy, however, are still poorly defined. AIM OF THE STUDY: To provide guidance to clinicians in the selection of maintenance therapy for newly diagnosed, advanced ovarian carcinoma. METHODS: A board of six gynecologic oncologists with expertise in the treatment of OC in Italy convened to address issues related to the new options for maintenance treatment. Based on scientific evidences, the board produced practice-oriented statements. Consensus was reached via a modified Delphi study that involved a panel of 22 experts from across Italy. RESULTS: Twenty-seven evidence- and consensus-based statements are presented, covering the following areas of interest: use of biomarkers (BRCA mutations and presence of homologous recombination deficiency); timing and outcomes of surgery; selection of patients eligible for bevacizumab; definition of response to treatment; toxicity and contraindications; evidence of synergy of bevacizumab plus PARP inhibitor. Two treatment algorithms are also included, for selecting maintenance therapy based on timing and outcomes of surgery, response to platinum-based chemotherapy and biomarker status. A score for the assessment of response to chemotherapy is proposed, but its validation is ongoing. CONCLUSIONS: We provide here consensus statements and treatment algorithms to guide clinicians in the selection of appropriate and personalized maintenance therapy in the first-line setting of advanced OC management.

Relationship of Inflammatory Parameters and Nutritional Status in Cancer Patients.

BACKGROUND/AIM: Chronic inflammation and cytokine storm can cause uncontrolled events in cancer. Pro-inflammatory molecules released by malignant cells send signals to the brain, liver, and neuroendocrine cells, interfering with appetite and promoting anorexia. Malnutrition in cancer patients is associated with increased treatment toxicity, reduced physical efficiency, and decreased survival. Therefore, early recognition of malnutrition could improve quality of life, treatment compliance, and survival. The aim of the study was to explore the relationship between inflammatory parameters with disease stage and nutritional status in patients with solid cancers. PATIENTS AND METHODS: We screened 77 consecutive patients from 3 clinical Institutions in Sicily, Italy, with solid tumors who were either in follow-up after curative treatment or being treated for metastatic disease using the Mini Nutritional Assessment (MNA) questionnaire. Inflammatory parameters, including interleukin 6 (IL6), C-reactive protein (CRP), ß2-microglobulin, ferritin, and transferrin were evaluated. RESULTS: A statistically significant difference was found in mean values of IL6, CRP, ß2-microglobulin, ferritin, and transferrin between patients without evidence of disease and metastatic patients. Among the metastatic group, there was a significant difference in mean values of these inflammatory parameters between patients with malnutrition and those with normal nutritional status. The difference in average IL6, CRP, ß2-microglobulin, and ferritin between patients at risk of malnutrition and those with normal nutritional status was also significant. However, the difference between patients at risk of malnutrition and those with malnutrition was not significant. CONCLUSION: IL6, CRP, transferrin, ferritin, and ß2-microglobulin are functional inflammatory parameters that indicate risk of malnutrition and support the MNA screening test to identify patients with solid tumors who require nutritional support.

Carboplatin-based doublet plus bevacizumab beyond progression versus carboplatin-based doublet alone in patients with platinum-sensitive ovarian cancer: a randomised, phase 3 trial.

BACKGROUND: Bevacizumab is approved in combination with chemotherapy for the treatment of ovarian cancer, either in first-line therapy or for patients with recurrent disease not previously treated with the same drug. We aimed to test the value of continuing bevacizumab beyond progression after first-line treatment with the same drug. METHODS: In our open-label, randomised, phase 3 trial done at 82 sites in four countries, we enrolled women (aged ≥18 years) who had previously received first-line platinum-based therapy including bevacizumab, and had recurrent (≥6 months since last platinum dose), International Federation of Gynaecology and Obstetrics stage IIIB-IV ovarian cancer with an Eastern Cooperative Oncology Group performance status 0-2. Patients were randomly assigned (1:1) to receive a carboplatin-based doublet intravenously (carboplatin area under the concentration curve [AUC] 5 on day 1 plus paclitaxel 175 mg/m2 on day 1, every 21 days; carboplatin AUC 4 on day 1 plus gemcitabine 1000 mg/m2 on days 1 and 8, every 21 days; or carboplatin AUC 5 on day 1 plus pegylated liposomal doxorubicin 30 mg/m2 on day 1, every 28 days), or a carboplatin-based doublet plus bevacizumab (10 mg/kg intravenous every 14 days combined with pegylated liposomal doxorubicin-carboplatin, or 15 mg/kg every 21 days combined with gemcitabine-carboplatin or paclitaxel-carboplatin). Evaluable disease according to RECIST 1.1 guidelines was required before randomisation. Randomisation was done through the trial website with a minimisation procedure, stratified by centre, time of recurrence, performance status, and type of second-line chemotherapy. The primary endpoint was investigator-assessed progression-free survival, analysed on an intention-to-treat basis. Safety was assessed in all participants who received at least one dose. This trial is registered with ClinicalTrials.gov, NCT01802749 and EudraCT 2012-004362-17. FINDINGS: Between Dec 6, 2013, and Nov 11, 2016, 406 patients were recruited (203 [50%] assigned to the bevacizumab group and 203 [50%] to the standard chemotherapy group). 130 patients (64%) in the bevacizumab group and 131 (65%) in the standard chemotherapy group had progressed after receiving a last dose of platinum more than 12 months before, and 146 patients (72%) in the bevacizumab group and 147 (72%) in the standard chemotherapy group had progressed after completion of first-line bevacizumab maintenance. 161 participants (79%) progressed in the standard chemotherapy group, as did 143 (70%) in the bevacizumab group. Median progression-free survival was 8·8 months (95% CI 8·4-9·3) in the standard chemotherapy group and 11·8 months (10·8-12·9) in the bevacizumab group (hazard ratio 0·51, 95% CI 0·41-0·65; log-rank p<0·0001). Most common grade 3-4 adverse events were hypertension (20 [10%] in the standard chemotherapy group vs 58 (29%) in the bevacizumab group), neutrophil count decrease (81 [41%] vs 80 [40%]), and platelet count decrease (43 [22%] vs 61 [30%]). 68 patients (33%) died in the standard chemotherapy group and 79 (39%) died in the bevacizumab group; two deaths (1%) in the standard chemotherapy group and one death (<1%) in the bevacizumab group were deemed to be treatment-related. INTERPRETATION: Continuing bevacizumab beyond progression combined with chemotherapy in patients with platinum-sensitive recurrent ovarian cancer improves progression-free survival compared with standard chemotherapy alone and might be considered in clinical practice. FUNDING: Hoffmann-La Roche and Associazione Italiana per la Ricerca sul Cancro.

Prognostic Factors for Adrenocortical Carcinoma Outcomes.

PURPOSE: Adrenocortical carcinoma (ACC) is an aggressive tumor characterized by a high recurrence rate and poor response to treatment. This study analyzes a consecutive series of ACC patients to evaluate the prognostic value of various clinical and pathological characteristics. METHODS: We retrospectively evaluated 32 ACC patients followed at our Medical Center from 1997 to 2015 and evaluated the prognostic value of age at diagnosis, gender, tumor functional status, stage, and type of treatment with respect to overall survival (OS) and disease-free survival (DFS), as determined by Kaplan-Meier curves. RESULTS: ACC was associated with hormonal overproduction in 50% of cases, and patients with isolated hyperandrogenism had a better prognosis. Recurrence was observed in 12/26 (46.2%) patients with no evidence of disease after surgery. Tumor size [hazard ratio (HR) 1.32, 95% confidential intervals (CI) 1.12-1.64; p = 0.007], ki-67 (HR 1.06, 95% CI 1.02-1.11; p = 0.009) and advanced stage at diagnosis (III-IV) (HR 6.51, 95% CI 1.65-24.68; p = 0.006) were associated with recurrence in the 26 R0 patients in the univariate analysis. Advanced stage was an independent risk factor for recurrence in the multivariate analysis (HR 8.10, 95% CI 1.55-41.35; p = 0.01). Five-year survival was 40.0%. Positive resection margins (HR 10.61, 95% CI 3.02-38.31; p = < 0.001), ki-67 (HR 1.04, 95% CI 1.01-1.07; p = 0.01) and advanced stage (HR 11.31, 95% CI 1.45-87.76; p = 0.02) were associated with poor survival in all 32 patients, but only positive resection margins were an independent predictor of mortality in the multivariate analysis (HR 6.22, 95% CI 1.44-26.05; p = 0.01). CONCLUSION: ACC has a poor prognosis with a high recurrence rate. Tumor stage at diagnosis and the completeness of surgical excision are the most relevant prognostic factors.

Pazopanib plus weekly paclitaxel versus weekly paclitaxel alone for platinum-resistant or platinum-refractory advanced ovarian cancer (MITO 11): a randomised, open-label, phase 2 trial.

BACKGROUND: Inhibition of angiogenesis is a valuable treatment strategy for ovarian cancer. Pazopanib is an anti-angiogenic drug active in ovarian cancer. We assessed the effect of adding pazopanib to paclitaxel for patients with platinum-resistant or platinum-refractory advanced ovarian cancer. METHODS: We did this open-label, randomised phase 2 trial at 11 hospitals in Italy. We included patients with platinum-resistant or platinum-refractory ovarian cancer previously treated with a maximum of two lines of chemotherapy, Eastern Cooperative Oncology Group performance status 0-1, and no residual peripheral neurotoxicity. Patients were randomly assigned (1:1) to receive weekly paclitaxel 80 mg/m(2) with or without pazopanib 800 mg daily, and stratified by centre, number of previous lines of chemotherapy, and platinum-free interval status. The primary endpoint was progression-free survival, assessed in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT01644825. This report is the final analysis; the trial is completed. FINDINGS: Between Dec 15, 2010, and Feb 8, 2013, we enrolled 74 patients: 37 were randomly assigned to receive paclitaxel and pazopanib and 37 were randomly assigned to receive paclitaxel only. One patient, in the paclitaxel only group, withdrew from the study and was excluded from analyses. Median follow-up was 16·1 months (IQR 12·5-20·8). Progression-free survival was significantly longer in the pazopanib plus paclitaxel group than in the paclitaxel only group (median 6·35 months [95% CI 5·36-11·02] vs 3·49 months [2·01-5·66]; hazard ratio 0·42 [95% CI 0·25-0·69]; p=0·0002). We recorded no unexpected toxic effects or deaths from toxic effects. Adverse events were more common in the pazopanib and paclitaxel group than in the paclitaxel only group. The most common grade 3-4 adverse events were neutropenia (11 [30%] in the pazopanib group vs one [3%] in the paclitaxel group), fatigue (four [11%] vs two [6%]), leucopenia (four [11%] vs one [3%]), hypertension (three [8%] vs none [0%]), raised aspartate aminotransferase or alanine aminotransferase (three [8%] vs none), and anaemia (two [5%] vs five [14%]). One patient in the pazopanib group had ileal perforation. INTERPRETATION: Our findings suggest that a phase 3 study of the combination of weekly paclitaxel plus pazopanib for patients with platinum-resistant or platinum-refractory advanced ovarian cancer is warranted. FUNDING: National Cancer Institute of Napoli and GlaxoSmithKline.

IL-6-174 G > C and MMP-9-1562 C > T polymorphisms are associated with increased risk of deep vein thrombosis in cancer patients.

BACKGROUND: A growing body of evidence shows an increased risk of deep vein thrombosis (DVT) among cancer patients. Novel markers are needed to identify patients prone to develop DVT. The aim of the present study was to determine whether IL-6-174 G > C and MMP-9-1562 C > T polymorphisms may influence the development of DVT in cancer patients. METHODS: Polymorphisms of IL-6 and MMP-9 were analyzed in 320 DNA samples from cancer patients (DVT+ and DVT-) and in 215 healthy donors. IL-6 and MMP-9 plasma levels were also measured by ELISA. RESULTS: Distribution of -174 IL-6 genotype and -1562 MMP-9 were similar between healthy controls and DVT- cancer cases (OR = 0.98 and 1.04, respectively). Different results were obtained by compared healthy controls with DVT+ cancer patients. -174 IL-6 GG polymorphism was associated to DVT (OR = 2.07; 95% CI: 1.30-3.30), as well as -1562 MMP-9 CC polymorphism (OR = 2.60; 95% CI: 1.48-4.57). CONCLUSION: The results of the present study support a model in which the GG and CC genotypes, respectively for IL-6-174 G > C and MMP-9-1562 C > T polymorphisms, are associated with a risk of DVT in cancer patients by inducing the release of IL-6 with subsequent increment of MMP-9. Overall, these findings may contribute to the management of DVT in cancer patients.

The Pathology of Medullary Carcinoma of the Thyroid: Review of the Literature and Personal Experience on 62 Cases.

The aim of the present review is to analyze the numerous pathological patterns of medullary carcinoma of the thyroid (MCT) and discuss the problems of differential diagnosis with other thyroid and nonthyroid tumors. In addition, morphological parameters and phenotypic features were related to the clinical outcome. The recent literature was reviewed and compared with the features of 62 MCTs observed at our institution. The most common patterns of growth are trabecular, alveolar and spindle cells, but MCT can mimic virtually all other primary thyroid tumors and some nonthyroid neoplasms. This heterogeneity has no proven implications for prognosis, but is of relevance for diagnostic purposes, as the differential diagnosis of MCT can be difficult in nonclassical cases. In agreement also with the literature data, no relationship between histopathological parameters and outcome was found in our series, although clinically aggressive tumors had a more advanced stage at presentation. Immunocytochemica demonstration of calcitonin is apparently the only valid criterion for a correct typing of MCT. Chromogranin A is an additional sensitive marker of MCT and parallels calcitonin expression in the majority of cases.