Delivering adjuvant and neoadjuvant treatments in the early stages of hepatocellular carcinoma.

INTRODUCTION: Hepatocellular carcinoma (HCC) presents a formidable challenge in oncology, demanding innovative treatment approaches. Both adjuvant and neoadjuvant therapies, thanks to the introduction of immunotherapy, have emerged as promising strategies in the management of HCC, aiming to reduce the risk of relapse and ultimately to improve survival. AREAS COVERED: This review considers current evidence, ongoing clinical trials, and future strategies to elucidate the evolving landscape of neoadjuvant and adjuvant treatments in HCC. EXPERT OPINION: Both adjuvant and neoadjuvant regimens, notably those incorporating immune checkpoint inhibitors, demonstrated encouraging safety profiles and efficacy outcomes in HCC.While significant challenges persist, including optimizing patient selection and endpoint definition, the evolving landscape of neoadjuvant and adjuvant therapy holds promise for maximizing the therapeutic potential of immunotherapy across all stages of HCC. Further insights into tumor biology and host immunity will shape the role of these approaches which are close to becoming reality in clinical practice.

The role of radiation therapy in the multidisciplinary management of male breast cancer: a systematic review and meta-analysis.

Male breast cancer (MaBC) is an uncommon disease. It is generally assimilated to post-menopausal female breast cancer and treated accordingly. However, the real impact of radiation therapy, after both mastectomy and breast conservation, has yet to be established. We performed a systematic review and meta-analysis to assess the clinical impact of radiation therapy in MBC patients to support the clinical decision-making process and to inform future research. We performed a systematic search of 'male', 'breast', 'cancer', 'radiotherapy' and corresponding synonyms on PubMed/MEDLINE and EMBASE databases. We included interventional studies reporting on radiation therapy effect on overall survival (OS) in MBC patients. Reviews, editorials, letters to the editor, conference abstracts and case reports, and studies with less than 20 MaBC patients or without data on OS were excluded. We extracted relevant characteristics and outcomes for each study, including the hazard ratio (HR) for OS, after adjustment for potential confounders. We calculated an overall adjusted hazard ratio (aHR) for OS for patients receiving radiation therapy compared to those who did not. A random effect model was used. The search strategy yielded 10,260 articles. After removal of duplicates (n = 8,254), 2,006 articles remained and underwent abstract screening. A total of 168 manuscripts was selected for full text screening. After full text screening, 22 articles were included in the qualitative systematic review. Among them, 14 were included in the quantitative synthesis, reporting on 80.219 MaBC patients. A statistically significant reduction in the risk of death was observed for patients receiving radiation therapy, with a pooled aHR = 0.73 (95%CI: 0.66-0.81) for OS. Significant heterogeneity among reported aHR estimates was seen (I2=77%). A significant clinical benefit on OS has been observed when including radiation therapy in the therapeutic algorithm of patients with MaBC. These findings, which are based on retrospective studies and tumour registry reports, deserve further investigation to identify MaBC patient subgroups who most benefit from radiation therapy.

[18F]FDG-PET/CT in adrenal lesions: diagnostic performance in different clinical settings.

PURPOSE: Data regarding [18F]FDG-PET/CT for the characterization of adrenal lesions are limited. Most of the studies proposed the tumor-to-liver maximum standardized uptake values (SUVratio) > 1.5 as the best cut off to predict malignancy. The aim of the study was to calculate the optimum cut off in a heterogeneous population with adrenal lesions and evaluate the diagnostic performance SUVratio >1.5. PATIENTS AND METHODS: Retrospective analysis of adrenal lesions undergoing [18F]FDG-PET/CT (2013-2022) for different reasons (atypical adrenal incidentalomas, extra adrenal tumor staging). The diagnosis of benignity was assessed by: (i) histology; (ii) stability or minimal diameter increase (<20%/<5 mm) on 12-months follow-up for non-operated patients. The optimal SUVratio and performance of SUVratio >1.5 were calculated by ROC curves. RESULTS: Forty-two consecutive lesions (diameter 36.1 ± 20.3 mm, 6 bilateral) underwent [18F]FDG-PET/CT (19F, age 61.2 ± 11.7 years). Twenty-nine lesions were benign, 11 malignant [8 metastases (2 bilateral) and 1 adrenocortical carcinoma (ACC)] and 2 pheochromocytomas. The SUVratio cut-off in our population was 1.55 (Sn 100%, Sp 73.7%, AUC 0.868), with similar values excluding pheochromocytomas and metastases (SUVratio cut-off 1.49, Sn 100%, Sp 96.3%, AUC 0.988). The SUVratio cut-off of 1.5 showed 100% Sn, 87% Sp, 73% PPV, and 100% NPV. CONCLUSION: [18F]FDG-PET/CT could help in decision making process avoiding unnecessary surgery. The SUVratio cut-off of 1.5 has a good performance in a heterogenous population.

HER2 status and response to neoadjuvant anti-HER2 treatment among patients with breast cancer and Li-Fraumeni syndrome.

BACKGROUND: Breast cancer (BC) is the most common cancer among females with Li-Fraumeni syndrome (LFS), but available data on LFS-related BC characteristics are derived from small retrospective cohorts. Prior work has demonstrated a high proportion of HER2-positive BCs, but our understanding of how HER2-positive LFS BCs respond to anti-HER2 treatments is limited. METHODS: BCs diagnosed in patients with germline TP53 variants between 2002-2022 were assembled from three institutions. Hormone receptor (HR) and HER2 expression were retrieved from pathology records. Pathologic complete response (pCR) was defined as ypT0/is ypN0. RESULTS: A total of 264 BCs were identified among 232 patients with LFS: 211 (79.9 %) were invasive carcinomas, of which 106 were HER2-positive. Among HER2-positive BCs, most tumors co-expressed HRs (72.6 %) and were more frequent among those diagnosed at younger age (p < 0.001). Mastectomy was the preferred surgical approach among women with nonmetastatic cancers (77.8 %) and most received anti-HER2 targeted therapy (74.7 %). Among 38 patients receiving neoadjuvant therapy with available post-treatment pathology reports, 27 (71.1 %) achieved pCR: 18/26 (69.2 %) among HR-positive and 7/10 (70.0 %) HR-negative. The rate of pCR was 84.6 % among patients treated with an anthracycline-free regimen (all received trastuzumab). Among classifiable HER2-negative BCs (n = 77), 31 (40.3 %) were HER2-low and 46 (59.7 %) HER2-zero. CONCLUSIONS: Among females with LFS and BC, HER2-positive subtype was associated with younger age at diagnosis and a predominant HR-positivity. Favorable pCR rates were observed among those receiving neoadjuvant HER2-directed therapies, for both HR-positive and negative tumors. These data may inform the counseling and care of patients with LFS.

Parp-inhibitors in the therapeutic landscape of breast cancer patients with BRCA1 and BRCA2 pathogenic germline variants: An Italian consensus paper and critical review.

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved medications and those with proven efficacy. This study utilized the Delphi method to present the first Italian consensus regarding genetic testing, the use of PARP inhibitors in both early and metastatic settings, and strategies for managing the potential toxicity of these novel drugs. The Panel unanimously agreed on various issues, including the timing, techniques, and patient characteristics for BRCA1/2 genetic testing, andthe appropriate placement of PARP inhibitors in the treatment algorithm for both early and advanced breast cancer. Nevertheless, some areas of divergence became evident, particularly regarding the use of axillary surgery for therapeutic purposes and the application of hormone replacement therapy in cases of bilateral mastectomy and risk-reducing salpingo-oophorectomy for patients treated for triple negative breast cancer. Additional research is needed in these particular domains to improve the care of patients with breast cancer who bear an increased genetic risk.

Serum Biomarkers to Dynamically Predict the Risk of Cardiovascular Events in Patients under Oncologic Therapy. A Multicenter Observational Study.

Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period. Methods: Patients undergoing anticancer therapies, either aged 75+ years old or younger with an increased CV risk according to European Society of Cardiology guidelines, were enrolled. We assessed the predictive value of biomarkers for the onset of CV events at baseline and during therapy using Cox model, Subpopulation Treatment-Effect Pattern Plot (STEPP) method and repeated measures analysis of longitudinal data. Results: From April 2018 to August 2021, 182 subjects were enrolled, of whom 168 were evaluable. Twenty-eight CV events were recorded after a median follow up of 9.2 months (Interquartile range, IQR: 5.1-14.7). Fibrinogen and troponin levels were independent risk factors for CV events. Specifically, patients with higher than the median levels of fibrinogen and troponin at baseline had higher risk compared with patients with values below the medians, hazard ratio (HR) = 3.95, 95% CI, 1.25-12.45 and HR = 2.48, 0.67-9.25, respectively. STEPP analysis applied to Cox model showed that cumulative event-free survival at 18 and 24 months worsened almost linearly as median values of fibrinogen increased. Repeated measure analysis showed an increase over time of D-Dimer (p-interaction event*time = 0.08), systolic (p = 0.07) and diastolic (p = 0.05) blood pressure and a decrease of left ventricular ejection fraction (p = 0.15) for subjects who experienced a CV event. Conclusions: Higher levels of fibrinogen and troponin at baseline and an increase over time of D-Dimer and blood pressure are associated to a higher risk of CV events in patients undergoing anticancer therapies. The role of OS in fibrinogen increase and the longitudinal monitoring of D-dimer and blood pressure levels should be further assessed.

"Positioning of tucatinib in the new clinical scenario of HER2-positive metastatic breast cancer: An Italian and Spanish consensus paper".

INTRODUCTION: Advancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly uncertain, influenced by various factors. METHODS: To refine HER2-positive metastatic breast cancer management, particularly regarding tucatinib's position, a Steering Committee of leading oncologists in breast cancer care devised a panel of statements via a Delphi approach, focusing on five key topics: general clinical management, therapeutic approaches for patients with HER2-positive breast cancer and brain metastases, treatment sequence, and tucatinib's safety and efficacy. RESULTS: A total of 29 statements were deliberated, with strong consensus achieved for most. However, no consensus emerged regarding the management of brain progression alongside stable extracranial disease: 48 % advocated for switching to tucatinib, while 53 % favored a stereotactic brain radiotherapy (SBRT) approach if feasible. CONCLUSION: The unanimous consensus attained in this Delphi panel, particularly regarding tucatinib's efficacy and safety, underscores oncologists' recognition of its clinical significance based on existing trial data. These findings align closely with current literature, shedding light on areas necessitating further investigation, not thoroughly explored in prior studies. Moreover, the results underscore the scarcity of data on managing brain progression alongside stable extracranial disease, emphasizing the imperative for dedicated research to address these gaps and yield definitive insights.

TP53-associated early breast cancer: new observations from a large cohort.

BACKGROUND: A recent large, well-annotated international cohort of patients with Li-Fraumeni syndrome and early-stage breast cancer was examined for shared features. METHODS: This multicenter cohort study included women with a germline TP53 pathogenic or likely pathogenic variant and nonmetastatic breast cancer diagnosed between 2002 and 2022. Clinical and genetic data were obtained from institutional registries and clinical charts. Descriptive statistics were used to summarize proportions, and differences were assessed using χ2 or Wilcoxon rank sum tests. Metachronous contralateral breast cancer risk, radiation-induced sarcoma risk, and recurrence-free survival were analyzed using the Kaplan-Meier methodology. RESULTS: Among 227 women who met study criteria, the median age of first breast cancer diagnosis was 37 years (range = 21-71), 11.9% presented with bilateral synchronous breast cancer, and 18.1% had ductal carcinoma in situ only. In total, 166 (73.1%) patients underwent mastectomies, including 67 bilateral mastectomies as first breast cancer surgery. Among those patients with retained breast tissue, the contralateral breast cancer rate was 25.3% at 5 years. Among 186 invasive tumors, 72.1% were stages I to II, 48.9% were node negative, and the most common subtypes were hormone receptor-positive/HER2-negative (40.9%) and hormone receptor positive/HER2 positive (34.4%). At a median follow-up of 69.9 months (interquartile range = 32.6-125.9), invasive hormone receptor-positive/HER2-negative disease had the highest recurrence risk among the subtypes (5-year recurrence-free survival = 61.1%, P = .001). Among those who received radiation therapy (n = 79), the 5-year radiation-induced sarcoma rate was 4.8%. CONCLUSION: We observed high rates of ductal carcinoma in situ, hormone receptor-positive, and HER2-positive breast cancers, with a worse outcome in the hormone receptor-positive/HER2-negative luminal tumors, despite appropriate treatment. Confirmation of these findings in further studies could have implications for breast cancer care in those with Li-Fraumeni syndrome.

Impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in patients with soft tissue sarcoma: an analysis from the OnCovid registry.

Background: To date, limited evidence exists on the impact of COVID-19 in patients with soft tissue sarcoma (STS), nor about the impact of SARS-CoV-2 vaccines and recent chemotherapy on COVID-19 morbidity and mortality in this specific population. Methods: We described COVID-19 morbidity and mortality among patients with STS across 'Omicron' (15 December 2021-31 January 2022), 'Pre-vaccination' (27 February 2020-30 November 2020), and 'Alpha-Delta' phase (01 December 2020-14 December 2021) using OnCovid registry participants (NCT04393974). Case fatality rate at 28 days (CFR28) and COVID-19 severity were also described according to the SARS-CoV-2 vaccination status, while the impact of the receipt of cytotoxic chemotherapy within 4 weeks prior to COVID-19 on clinical outcomes was assessed with Inverse Probability of Treatment Weighting (IPTW) models adjusted for possible confounders. Results: Out of 3820 patients, 97 patients with STS were included. The median age at COVID-19 diagnosis was 56 years (range: 18-92), with 65 patients (67%) aged < 65 years and most patients had a low comorbidity burden (65, 67.0%). The most frequent primary tumor sites were the abdomen (56.7%) and the gynecological tract (12.4%). In total, 36 (37.1%) patients were on cytotoxic chemotherapy within 4 weeks prior to COVID-19. The overall CFR28 was 25.8%, with 38% oxygen therapy requirement, 34% rate of complications, and 32.3% of hospitalizations due to COVID-19. CFR28 (29.5%, 21.4%, and 12.5%) and all indicators of COVID-19 severity demonstrated a trend toward a numerical improvement across the pandemic phases. Similarly, vaccinated patients demonstrated numerically improved CFR28 (16.7% versus 27.7%) and COVID-19 morbidity compared with unvaccinated patients. Patients who were on chemotherapy experienced comparable CFR28 (19.4% versus 26.0%, p = 0.4803), hospitalizations (50.0% versus 44.4%, p = 0.6883), complication rates (30.6% versus 34.0%, p = 0.7381), and oxygen therapy requirement (28.1% versus 40.0%, p = 0.2755) compared to those who were not on anticancer therapy at COVID-19, findings further confirmed by the IPTW-fitted multivariable analysis. Conclusion: In this study, we demonstrate an improvement in COVID-19 outcomes in patients with STS over time. Recent exposure to chemotherapy does not impact COVID-19 morbidity and mortality and SARS-CoV-2 vaccination confers protection against adverse outcomes from COVID-19 in this patient population.

An analysis from the OnCovid registry on the impact of chemotherapy and SARS-CoV-2 vaccines on clinical outcomes of patients with soft tissue sarcoma and COVID-19 Soft tissue sarcomas (STS) are a group of rare and aggressive tumours, usually treated with high dose cytotoxic chemotherapy. To date no clear evidence exists on the impact of COVID-19 in patients with STS, nor on the potential impact of recent chemotherapy and prior SARS-CoV-2 vaccination in this specific patient population. This is the 1st study to show COVID-19 outcomes in patients with STS, highlighting a substantial vaccine efficacy with no negative impact of recent chemotherapy on COVID-19 outcomes.

TEAM Study: Upfront Docetaxel Treatment in Patients With Metastatic Hormone-Sensitive Prostate Cancer: A Real-World, Multicenter, Retrospective Analysis.

BACKGROUND: Treatment of metastatic hormone-sensitive prostate cancer (mHSPC) dramatically changed. PEACE-1 and ARASENS trials established triplet therapy efficacy. Identifying prognostic factors supporting treatment choice is pivotal. METHODS: TEAM is an observational, retrospective study to evaluate prognostic role of variables in mHSPC patients receiving upfront docetaxel in 11 Italian centers. Outcome measures were progression-free survival (PFS) and overall-survival (OS). RESULTS: From September 2014 to December 2020, 147 patients were included. Median PFS and OS were 11.6 and 37.4 months. At univariate analysis, PFS-related variables were Gleason Score (GS) (P = .001), opioid use (P = .004), bone metastases number (P < .001), baseline PSA (P = .006), Hb (P < .001), ALP (P < .001) and LDH (P = .002), time between ADT and docetaxel start (P = .018), 3-month PSA (P < .001) and ALP (P < .001), and number of docetaxel cycles (P < .001). OS-related variables were PSA at diagnosis (P = .024), primary tumor treatment (P = .022), baseline pain (P = .015), opioid use (P < .001), bone metastases number (P < . 001), baseline Hb (P < .001), ALP (P < .001) and LDH (P = .001), NLR ratio (P = .039), 3-month PSA (P < .001) and ALP (P < .001) and docetaxel cycles number (P < .001). At multivariate analysis, independent prognostic variables were GS, opioid use, baseline LDH and time between ADT and docetaxel initiation for PFS, and baseline Hb and LDH for OS. CONCLUSION: Patients receiving upfront docetaxel with high GS, high disease burden, pain or opioid use, baseline unfavorable laboratory values had worse outcomes. Patients had greater docetaxel benefit when initiated early after ADT start. These parameters could be taken into account when selecting candidates for triplet therapy.

Previous immune checkpoint inhibitor therapy is associated with decreased COVID-19-related hospitalizations and complications in patients with cancer: Results of a propensity-matched analysis of the OnCovid registry.

OBJECTIVES: To date, studies have not provided definitive answers regarding whether previous immune checkpoint inhibitor (ICI) treatment alters outcomes for cancer patients with COVID-19. METHODS: The OnCovid registry (NCT04393974) was searched from February 27, 2020, to January 31, 2022, for patients who received systemic anti-cancer therapy in the 4 weeks before laboratory-confirmed COVID-19 diagnosis. Propensity-score matching using country, vaccination status, primary tumor type, sex, age, comorbidity burden, tumor stage, and remission status investigated differences in predefined clinical outcomes comparing those who had or had not received ICIs. RESULTS: Of 3523 patients screened, 137 ICI-only and 1378 non-ICI met inclusion criteria. Before matching, ICI patients were older, male, enrolled at centers in Italy, and had histories of smoking, thoracic cancers, advanced cancer stages, and active malignancies (P ≤0.02). After matching, there were 120 ICI and 322 non-ICI patients. ICI patients had no differences (odds ratio: 95% CI) in presenting COVID-19 symptoms (0.69: 0.37-1.28), receipt of COVID-specific therapy (0.88: 0.54-1.41), 14-day (0.95: 0.56-1.61), or 28-day (0.79: 0.48-1.29) mortalities. However, ICI patients required less COVID-19-related hospitalization (0.37: 0.21-0.67) and oxygen therapy (0.51: 0.31-0.83) and developed fewer complications (0.57: 0.36-0.92). CONCLUSION: In this propensity-score matched analysis, previous ICI therapy did not worsen and potentially improved COVID-19 outcomes in patients with cancer.

Essential requirements for reporting radiation therapy in breast cancer clinical trials: An international multi-disciplinary consensus endorsed by the European Society for Radiotherapy and Oncology (ESTRO).

The European Society for Radiotherapy and Oncology (ESTRO) has advocated the establishment of guidelines to optimise precision radiotherapy (RT) in conjunction with contemporary therapeutics for cancer care. Quality assurance in RT (QART) plays a pivotal role in influencing treatment outcomes. Clinical trials incorporating QART protocols have demonstrated improved survival rates with minimal associated toxicity. Nonetheless, in routine clinical practice, there can be variability in the indications for RT, dosage, fractionation, and treatment planning, leading to uncertainty. In pivotal trials reporting outcomes of systemic therapy for breast cancer, there is limited information available regarding RT, and the potential interaction between modern systemic therapy and RT remains largely uncharted. This article is grounded in a consensus recommendation endorsed by ESTRO, formulated by international breast cancer experts. The consensus was reached through a modified Delphi process and was presented at an international meeting convened in Florence, Italy, in June 2023. These recommendations are regarded as both optimal and essential standards, with the latter aiming to define the minimum requirements. A template for a case report form (CRF) has been devised, which can be utilised by all clinical breast cancer trials involving RT. Optimal requirements include adherence to predefined RT planning protocols and centralised QART. Essential requirements aim to reduce variations and deviations from the guidelines in RT, even when RT is not the primary focus of the trial. These recommendations underscore the significance of implementing these practices in both clinical trials and daily clinical routines to generate high-quality data.

Breaking barriers in triple negative breast cancer (TNBC) - Unleashing the power of antibody-drug conjugates (ADCs).

Antibody-drug conjugates (ADCs) represent a novel class of molecules composed of a recombinant monoclonal antibody targeted to a specific cell surface antigen, conjugated to a cytotoxic agent through a cleavable or non-cleavable synthetic linker. The rationale behind the development of ADCs is to overcome the limitations of conventional chemotherapy, such as the narrow therapeutic window and the emergence of resistance mechanisms. ADCs had already revolutionized the treatment algorithm of HER2-positive breast cancer. Currently, emergent non-HER2 targeted ADCs are gaining momentum, with special focus on triple-negative disease therapeutic landscape. Sacituzumab govitecan (SG) is an ADC consisting of a humanized monoclonal antibody hRS7 targeting trophoblast cell surface antigen 2 (Trop2), linked to the topoisomerase I inhibitor SN-38 by a hydrolysable linker. It currently stands as the only non-HER2 targeted ADC that already received approval for the treatment of unresectable locally advanced or metastatic triple negative breast cancer (TNBC) in patients who had received two or more prior systemic therapies, with at least one for advanced disease. The purpose of these review is to analyze the available evidence regarding ADCs in TNBC, alongside with providing an overview on the ongoing and future research horizons in this field.

Mechanisms of Resistance to Immunotherapy in Hepatocellular Carcinoma.

Systemic treatment for advanced hepatocellular carcinoma (HCC) has been revolutionized over the last few years following the approval of immune checkpoint inhibitors (ICI). Despite the promising survival extension seen with ICI combination regimens, responses are not universally seen and the optimal partner for programmed cell death 1 pathway inhibitors remains to be identified. Even fewer encouraging results have been demonstrated with ICI used for monotherapy. Several mechanisms of resistance have been described so far, involving characteristics of cancer cells (intrinsic mechanisms) and of the surrounding tumor microenvironment (extrinsic mechanisms). Factors related to therapy may also contribute to the development of resistance. Increasing research efforts are being dedicated to the discovery of novel approaches and targets to overcome resistance, some of which may be introduced into clinic in the future. Herein we describe a selection of resistance mechanisms that have been involved in impairing response to ICI and propose potential therapeutic approaches to overcome resistance.

Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients.

Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51-8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.

Capecitabine-Induced Ileitis during Neoadjuvant Pelvic Radio-Chemotherapy for Locally Advanced Rectal Cancer: A Case Report with Literature Review.

We report on a clinical case of capecitabine-induced acute ileitis in a patient treated with pre-operative concurrent chemoradiation with capecitabine for locally advanced rectal cancer and provide a comprehensive literature review. This a rare, but life-threatening, clinical situation, that clinicians should be aware of. Severe persistent diarrhea is the most frequent clinical feature and computed tomography is a valid tool for diagnosis. Conservative management includes capecitabine withdrawal, antidiarrheal therapy and endovenous hydration, together with dietary modifications and broad-spectrum antibiotics. Pelvic irradiation represents an adjunctive risk factor, which may increase the likelihood of occurrence of terminal ileitis. Early recognition and prompt intervention are crucial for successful clinical management.

Weight Management Effectiveness and Predictors of Dropout in Breast Cancer Survivors: A Retrospective Study.

BACKGROUND: Reducing obesity and weight gain, which often occurs during breast cancer treatment, may represent an efficient secondary or tertiary prevention against cancer. PURPOSE: This retrospective observational cohort study aimed to assess the impact of a Mediterranean diet on weight and anthropometric changes in women completing active breast cancer treatment. Additionally, we sought to identify factors associated with study dropout within one year. METHODS: A total of 182 female patients (20 normal weight, 59 overweight, 103 obese) received personalized Mediterranean diet interventions and underwent monthly outpatient visits. RESULTS: Dropout rates were 42.3% at 6 months and 64.1% at 12 months. Among the obese subgroup, BMI (p < 0.001) and fat mass (p < 0.05) decreased after 6 months. At 12 months, the obese subgroup showed a borderline significant further reduction in BMI (p = 0.062). BMI or weight loss did not predict dropout at any time point. However, age (OR = 0.91) and diastolic blood pressure (OR = 1.07) were significant predictors of dropout at 12 months. CONCLUSION: Implementing a Mediterranean diet can lead to weight and anthropometric improvements in breast cancer survivors. Further research is necessary to explore the long-term effects of weight loss on these individuals, identify effective dietary approaches, and consider specific predictors of dropout.

Tucatinib's journey from clinical development to clinical practice: New horizons for HER2-positive metastatic disease and promising prospects for brain metastatic spread.

Approximately 20% of breast cancers (BCs) overexpress human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein with tyrosine kinase activity, encoded by ERBB2 gene. Historically, HER2 overexpression has been linked with increased disease recurrence and a worse prognosis. However, the increasing availability of different anti-HER2 compounds and combinations is progressively improving HER2-positive BC outcome, thus requiring expertise to prioritize both overall survival (OS) prolongation and quality of life, without neglecting the accessibility to further treatment lines with a low attrition rate. In this context, tucatinib, an oral tyrosine kinase inhibitor, has recently been granted approval by regulatory agencies based on evidence from the HER2CLIMB, a clinical trial which randomized patients with metastatic BC to receive trastuzumab and capecitabine with either tucatinib or placebo. A distinctive feature of this study was the inclusion of patients with new or active brain metastases (BMs) at study entry, a population traditionally excluded from clinical trials. Thus, HER2CLIMB provides the first solid evidence of an OS benefit in patients with BC and BMs, addressing a long standing unmet medical need, especially given the high incidence of central nervous system metastatic spread in patients with HER2-positive disease. This review provides an overview of the molecular and clinical landscape of tucatinib for the treatment of advanced BC. It focuses on the technological journey that drove the development of this therapeutic innovation, from preclinical data to clinical practice.