Oral anticancer therapy project: Clinical utility of a specific home care nursing programme on behalf of Italian Association of Medical Oncology (AIOM).

AIMS AND OBJECTIVES: To assess the effectiveness of a specific home care nursing programme in addition to standard care in patients (pts) receiving oral anticancer treatments. BACKGROUND: Oral anticancer therapy present challenges for pts since treatment is a home-based therapy. This study evaluates the potentiality of a home care nursing programme in decreasing hospital accesses for not severe toxicity. METHODS: This is an open-label, multicentre, randomised trial including pts who were receiving an anticancer oral drug. The study complies with the CONSORT checklist published in 2010. Concomitant use of radiation therapy, intravenous or metronomic therapies, or the intake of previous oral drugs was not allowed. Pts were randomly assigned to home care nursing programme (A) or standard care (B). In arm A, dedicated nurses provided information to pts, a daily record on which pts would take note of drugs and dosages and a telephone monitoring during the first two cycles of therapy. The primary outcome was the reduction in improper hospital accesses for grade 1-2 toxicity according to CTCAE v4.0. RESULTS: Out of 432 randomised pts, 378 were analysed (184 pts in arm A and 194 in arm B). Hospital accesses were observed in 41 pts in arm A and in 42 pts in arm B (22.3% vs. 21.6%, respectively). No difference was detected in proportion of improper accesses between arm A and arm B (29.3% vs. 23.8%, respectively). CONCLUSIONS: Our experience failed to support the role of a specific home care nursing programme for pts taking oral chemotherapy. An improved attention to specific educational practice and information offered to pts can explain these results. RELEVANCE TO CLINICAL PRACTICE: Our results underline the role of nurse educational practice and information offered to patients. A careful nurse information of patients about drugs is essential to reduce toxicities avoiding the opportunity of a specific home monitoring.

Anti-PD-1 versus anti-PD-L1 therapy in patients with pretreated advanced non-small-cell lung cancer: a meta-analysis.

Aim: At present three immune checkpoint inhibitors (ICIs), two anti-PD-1 (nivolumab and pembrolizumab) and one anti-PD-L1 (atezolizumab) can be used in pretreated non-small-cell lung cancer patients. The aim of this meta-analysis is an indirect comparison between anti-PD-1 and anti-PD-L1 inhibitors. Methods: Seven studies (>4000 patients) were considered. Results: Considering the overall survival ICIs showed very robust efficacy over docetaxel, while in terms of progression-free survival the therapy with ICIs is slightly favored. Anti-PD-1 gives a more significant benefit than anti-PD-L1; however, excluding the KEYNOTE 010 trial that enrolled only PD-L1-positive patients, the subgroup difference remains only in terms of progression-free survival. Conclusion: This meta-analysis confirms the superiority of ICIs over docetaxel in pretreated non-small-cell lung cancer patients and would indicate a slight benefit from anti-PD-1 than from anti-PD-L1 inhibitors, always keeping in mind the possible biases of this indirect comparison.

Crizotinib-induced cardiotoxicity: the importance of a proactive monitoring and management.

Crizotinib is a multitarget tyrosine kinase inhibitor and it represents the standard of care in patients with anaplastic lymphoma kinase translocated non-small-cell lung cancer. Crizotinib is generally well tolerated and the most frequent adverse events include gastrointestinal effects, visual disorders, edema, fatigue and liver enzyme abnormalities. However, due to the increasing clinical experience with crizotinib, other toxicities are emerging, such as Q-wave T-wave interval prolongation and bradycardia. In the current review we will focus on the management of crizotinib-related cardiotoxicity.

Long-term survival in small cell lung cancer: a case report and review of the literature.

Small cell lung cancer (SCLC) represents approximately 13% of all newly diagnosed lung cancers. SCLC is a very aggressive disease characterized by early locoregional and distant metastases. The median survival is 14-16 months for patients with limited disease and 8-11 months for those with extensive disease, with 20-40% of patients with limited disease and 5% of patients with extensive disease alive at 2 years. This report discusses the case of a long-term SCLC survivor treated with radiotherapy, several lines of chemotherapy and long-acting somatostatin analogs who is alive 7 years after diagnosis, with no evidence of further relapse. In the near future, better identification of prognostic and predictive factors based on models that integrate clinical data and multiple gene expression profiles and the use of novel treatments could increase the number of long-term SCLC survivors.

Identification of a prognostic DNA repair gene signature in esophageal cancer.

Background: DNA repair plays a crucial role in the development and progression of different types of cancers. Nevertheless, little is known about the role of DNA repair-related genes (DRRGs) in esophageal cancer (EC). The present study aimed to identify a novel DRRGs prognostic signature in EC. Methods: Gene set enrichment analysis (GSEA) was performed to screen 150 genes related to DNA repair, which is the most important enrichment gene set in EC. Univariate and multivariate Cox regression analyses were used to screen DRRGs closely associated with prognosis. The difference in the expression of hub DRRGs between tumor and normal tissues was analyzed. Combined with clinical indicators (including age, gender, and tumor stage), we evaluated whether the 4-DRRGs signature was an independent prognostic factor. In addition, we evaluated the prediction accuracy using a receiver operating characteristic (ROC) curve and visualized the model's performance via a nomogram. Results: Four-DRRGs (NT5C3A, TAF9, BCAP31, and NUDT21) were selected by Cox regression analysis to establish a prognostic signature to effectively classify patients into high- and low-risk groups. The area under the curve (AUC) of the time-dependent ROC of the prognostic signature for 1- and 3-year was 0.769 and 0.720, respectively. Compared with other clinical characteristics, the risk score showed a robust ability to predict the prognosis in EC, especially in the early stage of EC. Furthermore, we constructed a nomogram to interpret the clinical application of the 4-DRRGs signature. Conclusions: In conclusion, we identified a prognostic signature based on the DRRGs for patients with EC, which can contribute independent value in identifying clinical outcomes that complement the TNM system in EC.

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research.

INTRODUCTION: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). METHODS AND OBJECTIVES: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. CONCLUSION: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project.

Role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity: two cases and review of the literature.

Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor. Our experience confirms that inhibition of angiogenic factors to treat cancer is a novel challenge for the oncologist and requires the cardiologist's support.

Current Treatment Approaches for Thymic Epithelial Tumors.

Thymic epithelial tumors (TETs), including thymoma, thymic carcinoma and neuroendocrine tumors, are uncommon tumors that originate from the epithelial cells of the thymus. Nevertheless, despite their rarity, they represent the most common tumor type located in the anterior mediastinum. Therapeutic choices based on staging and histology may include surgery with or without neoadjuvant or adjuvant therapy represented by chemotherapy, radiotherapy or chemo-radiotherapy. For patients with advanced or metastatic TETs, platinum-based chemotherapy remains the standard first-line treatment; however, some new drugs and combinations are currently under evaluation. In any case, proper management of patients with TETs requires a multidisciplinary team approach to personalize care for each patient.

Psychological Well-Being of Cancer Patients before and during the Pandemic: The Impact of COVID-19 Peritraumatic Distress.

BACKGROUND: This study aimed to evaluate the psychological impact of the COVID-19 pandemic on cancer patients. METHODS: Ninety cancer patients undergoing chemotherapy with antiblastics were recruited from a tertiary medical center and completed a battery of standardized questionnaires to assess anxiety, depression, peritraumatic stress, and quality of life before and during the pandemic. RESULTS: Quality of life worsened significantly during the pandemic compared with the pre-pandemic period. Anxiety and depression levels also increased significantly during the pandemic. COVID-19 peritraumatic distress significantly predicted lower quality-of-life scores during the pandemic. CONCLUSIONS: COVID-19 distress affected the overall quality of life of patients who already had lower levels of quality of life before the pandemic and who had advanced cancers. Cancer patients must receive adequate support from psychiatrists and psychologists to mitigate the psychological distress related to the pandemic.

Association between cigarette smoking history, metabolic phenotypes, and EGFR mutation status in patients with non-small cell lung cancer.

Background: Cigarette smoking exerts a significant impact on metabolic phenotypes and epidermal growth factor receptor (EGFR) mutation status; however, their correlation remains insufficiently established. Therefore, the aim of this study was to investigate the association between cigarette smoking history, metabolic phenotypes, and EGFR mutation status in patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively analyzed 198 consecutive patients with NSCLC who underwent 18F-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) before treatment and were tested for EGFR mutation status between September 2019 and March 2022. Metabolic phenotypes, including the maximum standardized uptake value (SUVmax) of the primary tumors (pSUVmax), metastatic lymph nodes (nSUVmax), and distant metastases (mSUVmax) were assessed. Patients were classified into never-smokers and smokers based on detailed smoking history. The correlations between smoking status, metabolic parameters, and EGFR mutation status were evaluated in patients with NSCLC. Results: We observed EGFR mutations in 73 (60.3%) of 121 never-smokers and 18 (23.4%) of 77 smokers (P<0.001). EGFR-mutant NSCLC had a lower pSUVmax than that of EGFR wild-type (WT; 8.9±4.5 vs. 12.7±6.9, P<0.001). Smokers had a higher pSUVmax than never-smokers (12.5±6.4 vs. 9.9±5.9, P=0.004). With the increase of cumulative smoking dose, the pSUVmax increased significantly (r=0.198, P=0.005). There was no significant difference between nSUVmax and mSUVmax in patients with or without EGFR mutation and smoking history. Cumulative smoking dose, pSUVmax, and their combination predicted EGFR mutation status with areas under the receiver operating characteristic (ROC) curves (AUCs) 0.688, 0.673, and 0.753, respectively. Conclusions: Our findings indicate that cigarette smoking may be one of the triggers for increased pSUVmax and decreased EGFR mutations, further suggesting that EGFR mutations are associated with low pSUVmax, which may guide clinicians in risk stratification and treatment strategy selection for patients with NSCLC.

Progenitor-like exhausted SPRY1+CD8+ T cells potentiate responsiveness to neoadjuvant PD-1 blockade in esophageal squamous cell carcinoma.

Neoadjuvant immune checkpoint blockade (ICB) demonstrates promise in operable esophageal squamous cell carcinoma (ESCC), but lacks available efficacy biomarkers. Here, we perform single-cell RNA-sequencing of tumors from patients with ESCC undergoing neoadjuvant ICB, revealing a subset of exhausted CD8+ T cells expressing SPRY1 (CD8+ Tex-SPRY1) that displays a progenitor exhausted T cell (Tpex) phenotype and correlates with complete response to ICB. We validate CD8+ Tex-SPRY1 cells as an ICB-specific predictor of improved response and survival using independent ICB-/non-ICB cohorts and demonstrate that expression of SPRY1 in CD8+ T cells enforces Tpex phenotype and enhances ICB efficacy. Additionally, CD8+ Tex-SPRY1 cells contribute to proinflammatory phenotype of macrophages and functional state of B cells, which thereby promotes antitumor immunity by enhancing CD8+ T cell effector functions. Overall, our findings unravel progenitor-like CD8+ Tex-SPRY1 cells' role in effective responses to ICB for ESCC and inform mechanistic biomarkers for future individualized immunotherapy.

Off-label use of anti-cancer drugs between clinical practice and research: the Italian experience.

BACKGROUND: Off-label use is the practice of prescribing a drug outside the terms of its official labeling. Worldwide, about 20% of the commonly prescribed medications are off-label, and the percentage increases in specific patient populations, such as children, pregnant women, and cancer patients. Off-label use is particularly widespread in oncology for many reasons, including the wide variety of cancer subtypes, the difficulties involved in performing clinical trials, the rapid diffusion of preliminary results, and delays in the approval of new drugs by regulatory organizations/agencies. OBJECTIVE: The aim of this article is to describe the use of off-label drugs in oncology, with an emphasis on the role of the world's leading regulatory agencies and an assessment of current Italian legislation. CONCLUSION: Off-label drug utilization is essential in oncology when based on evidence. However, off-label drugs must be prescribed in accordance with existing national laws and only when the potential benefit outweighs the potential toxic effects.

Anal metastasis from breast cancer: a case report and review of the literature.

Breast cancer usually metastasizes towards the lymph nodes, lung, bone, liver or brain; metastatic gastrointestinal involvement is rare and anal metastases are extremely rare. Necroscopic studies report a 6-18% incidence of extra-hepatic gastrointestinal metastases, and the most frequent sites of the GI tract involved are the stomach and the small intestine. We report a case with anal metastasis from breast cancer and a review of the associated literature.

Decisions and dilemmas in non-metastatic castration-resistant prostate cancer management.

Non-metastatic castration-resistant prostate cancer (nmCRPC) indicates a condition characterized by the progression of the prostate-specific antigen without radiographic evidence of distant metastasis on conventional imaging during androgen deprivation therapy (ADT). Recently, 3 phase III trials have shown that the addition of next-generation androgen-receptor inhibitors (ARIs) apalutamide, darolutamide, and enzalutamide to ADT allows patients with high-risk nmCRPC to delay the appearance of metastasis and to obtain long-term clinical benefits. However, the lack of head-to head comparison makes it difficult to choose one among these agents. We reviewed the literature and explained the rationale of the possible therapeutic choices. In any case, the availability of novel ARIs means that patients with nmCRPC have now a new effective treatment option that provides them a renewed hope.

Management of oligoprogression in non-small cell lung cancer patients.

Oligoprogression is an emerging concept in oncology representing a state where after an initially successfully local or systemic treatment a disease progression occurs characterized by the appearance of a single or few new lesions. We reviewed the literature and explained the rationale of the therapeutic choices by referring to the current guidelines and literature data. In any case, the treatment of oligometastatic disease should be tailored to suit the individual patient with the aim of maximizing the benefit of each line of therapy.

Potential Role of Tumor-Derived Exosomes in Non-Small-Cell Lung Cancer in the Era of Immunotherapy.

Lung cancer, of which non-small-cell lung cancer (NSCLC) represents about 80% of all cases, is the second most common cancer diagnosed in the general population and one of the major causes of cancer-related deaths worldwide. Overall, the outcomes of patients with advanced NSCLC are still disappointing despite advances in diagnosis and treatment. In recent years immune-checkpoint inhibitors (ICIs), administered alone or in combination with chemotherapy, have revolutionized the treatment landscape of patients with advanced non-small-cell lung cancer. However, until now, tissue expression of PD-L1 and tumor mutation burden represent the only available biomarkers for NSCLC patients treated with ICIs. A growing body of evidence showed that tumor-derived exosomes (TDEs) have the PD-L1 protein on their surface and that they are involved in angiogenesis, tumor growth, invasion, metastasis and immune escape. This review focused on the potential clinical applications of TDEs in NSCLC, including their possible role as a biomarker for prognosis and disease monitoring in patients undergoing immunotherapy.

Circulating tumor cells can predict the prognosis of patients with non-small cell lung cancer after resection: a retrospective study.

BACKGROUND: The development of metastasis is the primary cause of death in patients with non-small cell lung cancer (NSCLC). However, identifying those NSCLC patients who will have loco-regional or distant disease recurrence after surgery is still challenging. Circulating tumor cells (CTCs) can accurately reflect the impact of micro-metastasis of tumor cells in circulating blood on patients' treatment and prognosis. The aim of the present study was to explore the value of preoperative CTC concentration in predicting postoperative metastasis and recurrence risk in patients with NSCLC. METHODS: This study enrolled 347 patients with stage I-IIIA NSCLC. The CTCs were isolated using folate receptor (FR) positivity from peripheral blood samples before surgery, and then enriched and analyzed. Patients were divided into two groups for retrospective survival analysis based on the geometric mean of CTC concentration. The primary study endpoint was recurrence-free survival. Spearman's correlation was used to evaluate the relationship between CTC concentration and clinical characteristics of NSCLC patients. A nomogram based on the multivariate Cox regression model was developed to predict recurrence and metastasis in the NSCLC patients. The performance of the nomogram was evaluated using the concordance index, calibration curve, and Hosmer-Lemeshow test. RESULTS: The median follow-up time was 38 months. Preoperative CTC concentration was not significantly related to tumor-node-metastasis staging (P>0.05) and was an independent prognostic factor for NSCLC patients [hazard ratio (HR), 5.489; 95% confidence interval (CI): 2.660-11.326, P<0.001]. The nomogram based on preoperative CTC concentration had a concordance index value of 0.82. Validation revealed that the nomogram possessed excellent predictive ability and calibration. CONCLUSIONS: Preoperative CTC concentration is an independent and sensitive biomarker of prognosis in patients with NSCLC. Our nomogram based on preoperative CTC concentration is an effective and non-invasive tool for predicting the recurrence and metastasis of NSCLC.

Metaplastic breast cancer. A case series.

Special type breast cancers display a wide range of different histological types in which clear recommendations on clinical and therapeutic management still lack and most of the information available derive from case report and case studies. In particular metaplastic breast cancer (MBC) is a rare and aggressive type of breast cancer accounting for around 1% of breast malignancies. We reported our experience in the management of five patients with MBC diagnosed and treated in our institution during the last few years (2016-2020). KEY WORDS: Metaplastic breast cancer, Special type breast cancers.

Beyond Conventional: The New Horizon of Targeted Therapy for the Treatment of Advanced Non Small Cell Lung Cancer.

In the last few years the advent of targeted therapies against oncogenic drivers significantly improved the survival of non small cell lung cancer (NSCLC) patients with a favourable toxicity profile. Therefore, genetic testing, including at least EGFR mutations and ALK/ROS1 rearrangements, should be performed in all NSCLC patients (in particular with adenocarcinoma) who received a diagnosis of advanced disease. This review focuses on novel druggable oncogenic drivers, such as MET exon 14 mutations/MET amplification, RET fusions, BRAF V600E mutations, KRAS G12C mutations, NTRK rearrangements, and HER2 alterations.

Octogenarians may benefit from stage-specific small cell lung cancer treatment.

BACKGROUND: Our study investigates treatment profiles in octogenarian patients with small cell lung cancer (SCLC) and assesses each treatment's role in a stage-specific manner. METHODS: Patient data from individuals with SCLC aged 80 years and older between 1988 and 2015 in the Surveillance, Epidemiology, and End Results Program (SEER) database were extracted. Cancer-specific survival (CSS) between patients with no treatment and different treatment groups were compared by the Kaplan-Meier method, with stratifications by stage. Cox Proportional Hazard model further identified independent prognostic factors. RESULTS: A total of 7,290 patients were included in this study. Notably, 3,358 (46.1%) patients did not receive active treatment. Compared with the no active treatment group, the CSS of patients who received treatment was significantly improved (median 6 vs. 0 months, P<0.001) and further validated in stage subgroups. Chemotherapy combined with local therapy was associated with the best CSS in regional and distant disease stages, with the hazard ratios (HR) and 95% confidence intervals (CI) being 0.30 (0.26-0.34) and 0.27 (0.25-0.30), respectively. Local therapy only appeared to confer better oncological outcomes (HR =0.33; 95% CI: 0.25-0.42) than chemotherapy only (HR =0.37; 95% CI: 0.29-0.47) in the localized disease stage. CONCLUSIONS: Although nearly half of octogenarians with SCLC did not receive active treatment in the real clinical setting, these patients may benefit from treatment. Chemotherapy combined with local therapy may provide the best treatment choice in octogenarians with advanced SCLC, while local therapy appears to play a more critical role in treating those with early-stage disease.