Sirolimus experience in adult patients with vascular malformations.

AIM: Sirolimus, a mammalian target of rapamycin inhibitor, inhibits cell growth and proliferation by controlling ribosome biogenesis and protein synthesis in vascular anomalies and cancers. However, most sirolimus studies on vascular anomalies were conducted in the pediatric population, with limited data in adults. In this study, we assessed the effectiveness and safety of sirolimus in adult patients with vascular malformation, a subtype of vascular anomaly. METHODS: We conducted a retrospective analysis of adult vascular malformation patients aged over 16, treated at Hacettepe University Cancer Institute from January 2013 to September 2022. Patient demographics and clinical characteristics were recorded. The primary outcome was the efficacy of sirolimus evaluated by response and disease control rates. The disease control rate was defined as the cumulative percentage of complete or partial responses, along with stable disease. The secondary endpoint was toxicity and safety. RESULTS: 38 patients with a median age of 21 (IQR: 18-33) were recruited. Prior to sirolimus treatment, 57.9% of patients had undergone other therapeutic interventions, predominantly sclerotherapy and surgery. The median follow-up time during sirolimus treatment was 18.5 (IQR: 11.3-74.5) months. The disease control rate was 92.1% (35/38). Head-neck localization was associated with better response rates (p = .001). Sirolimus was generally well tolerated and grade 1 or 2 oral mucositis (n = 4) and skin rash (n = 3) were the most common side effects. CONCLUSION: In this study, we found sirolimus was efficacious and well tolerated in adult patients with vascular malformation.

The efficacy of palbociclib and ribociclib in the first-line treatment of metastatic hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer in male patients: a Turkish oncology group (TOG) study.

INTRODUCTION: Male breast cancer, comprising approximately 1% of all breast cancer cases, often leads to the exclusion of male patients as a criterion in clinical trials. While the efficacy of Cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors has been established in metastatic hormone receptor-positive (HR +) and human epidermal growth factor receptor 2-negative (HER2 -) breast cancer in women, limited data exist on their effectiveness in male patients. We aimed to evaluate the efficacy and safety of palbociclib or ribociclib in male patients with breast cancer. METHODS: This study is a multicenter, retrospective study. We included male patients with HR + and HER2-metastatic breast cancer who received palbociclib or ribociclib as first-line treatment. Our primary endpoints were progression-free survival (PFS), overall response rates (ORR), and drug-related adverse effects. RESULTS: A total of 46 male patients from 27 institutions were enrolled. The median age at initiation of CDK 4/6 inhibitors was 63.64 ± 13.69 years, with a median follow-up of 21.33 (95% CI 14.92-27.74) months. The ORR were 84% for palbociclib and 76.2% for ribociclib. The mPFS for the entire cohort was 28.06 months (95% CI 18.70-37.42). No significant difference in PFS was observed between palbociclib and ribociclib (mPFS: 24.46 months (95% CI 11.51-37.42) vs 28.33 months (95% CI 14.77-41.88), respectively, p = 0.211). No new adverse events were reported. DISCUSSION: This study demonstrates that palbociclib and ribociclib are effective and safe options for first-line treatment in male patients with HR + /HER2 - metastatic breast cancer. However, further prospective studies are warranted to establish their efficacy in this population.

Mean Platelet Volume to Lymphocyte Ratio: A New Biomarker Predicting Response in Patients with Solid Tumors Treated with Nivolumab.

Introduction: Although immune checkpoint inhibitors (ICIs) are widely used in cancer treatment, identifying factors that predict treatment response remains a challenge in clinical practice. There is a need for biomarkers to identify patients who may not benefit from these treatments. It is crucial to identify a simple and cost-effective biomarker that can be easily incorporated into clinical practice. This study aims to investigate the mean platelet volume to lymphocyte ratio (MPVLR), as measured by a hemogram test, and median overall survival (mOS) in patients with cancer treated with nivolumab. Methods: A total of 131 adult patients with metastatic cancer, including malignant melanoma (MM), renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), and head and neck cancer (HNC), were included in this study. Baseline demographics, ECOG (Eastern Cooperative Oncology Group) performance status, tumor type, and blood count parameters were recorded. Univariate and multivariate analyses were conducted to evaluate potential risk factors. Results: The median age of the patients was 59.87 ± 11.97 years, and the median follow-up period was 20.20 months (IQR, 12.80-27.60). RCC (43.5%) and MM (25.9%) were the most common diagnoses. Patients with ECOG scores of 0-1 had a longer mOS than those with scores of 2-3 (mOS: 20.60 months [95% CI, 14.94-25.29] vs. 5.24 months [95% CI, 0-16.42], p < 0.001). Additionally, patients with lactate dehydrogenase (LDH) levels within the normal range had a longer mOS than those with high LDH levels (mOS: 24.54 months [95% CI, 14.13-34.96] vs. 13.10 months [95% CI, 4.49-21.72], p = 0.038). Patients with low MPVLR also had a longer mOS than those with high MPVLR (mOS: 33.70 months [95% CI, 25.99-41.42] vs. 11.07 months [95% CI, 6.89-15.24], p < 0.001). In the multivariate Cox regression analysis, high MPVLR, ECOG score of 2-3, and high LDH level were associated with shorter mOS (p < 0.001, p = 0.001, and p = 0.046, respectively). Conclusion: This study demonstrates that MPVLR could serve as a novel biomarker for predicting response to nivolumab treatment. Incorporating MPVLR into clinical practice may aid in identifying patients who are less likely to benefit from the treatment.

KELIM score predicts outcome in patients with platinum-resistant/refractory recurrent ovarian cancer.

Aim: To assess the prognostic role of the CA-125 elimination rate constant K (KELIM) score in platinum-resistant/refractory ovarian cancer patients receiving second-line treatment. Methods: A retrospective study was carried out including 117 patients with advanced-stage platinum-resistant/refractory ovarian cancer treated with liposomal doxorubicin ± bevacizumab. The KELIM score, calculated using CA-125 measurements within the first 100 days of chemotherapy, was used. Survival analyses were performed for overall survival (OS) and progression-free survival (PFS). Results: Higher KELIM scores were associated with a superior PFS and OS. Multivariate analysis confirmed the independent prognostic value of the KELIM score for OS. Validation cohorts showed consistent results. Conclusion: KELIM score may serve as a valuable prognostic marker for predicting OS and PFS in platinum-resistant/refractory ovarian cancer patients receiving second-line treatment. Prospective studies are needed for validation.

This study aimed to investigate the usefulness of a scoring system called CA-125 elimination rate constant K (KELIM) in predicting the outcomes of ovarian cancer patients who are resistant to or have not responded to platinum-based treatments and are receiving a second-line treatment. The researchers conducted a retrospective (backwards looking) study involving 117 patients with advanced-stage ovarian cancer. They analyzed the patients' CA-125 levels within the first 100 days of chemotherapy to calculate the KELIM score. The results showed that higher KELIM scores were associated with better progression-free survival (the length of time during and after the treatment of a disease, that a patient lives with the disease but it does not get worse) and overall survival (the length of time from either the date of diagnosis or the start of treatment for a disease that patients diagnosed with the disease are still alive). Further analysis confirmed that the KELIM score was an independent predictor of overall survival. The findings were consistent when validated with additional patient groups. In conclusion, the KELIM score has the potential to be a useful tool for predicting the outcomes of ovarian cancer patients undergoing second-line treatment. However, further prospective studies are necessary to validate these findings.

Do statins enhance the antitumor effect of trastuzumab emtansine (T-DM1)?: Real-life cohort.

Human epidermal growth factor receptor 2 (HER2)-targeting therapies have become crucial in the management of HER2-positive breast cancer. Trastuzumab emtansine (T-DM1) is a microtubule inhibitor and HER2-targeted antibody conjugate. T-DM1 resistance is most likely influenced by factors involved in the biological mechanisms of T-DM1 action. This study aimed to examine the efficacy of statins, which influence HER-2-based therapies via the caveolin-1 (CAV-1) protein, in female breast cancer patients receiving T-DM1. Our study included 105 patients with HER2-positive metastatic breast cancer treated with T-DM1. The progression-free survival (PFS) and overall survival (OS) of patients who received statins concurrently with T-DM1 versus those who did not were compared. During the median 39.5 (95% confidence interval [CI]: 35.6-43.5) months of follow-up, 16 (15.2%) patients received statins, and 89 (84.8%) patients did not. Median OS was significantly higher in patients using statins than in patients not using statins (58.8 vs 26.5 months, P = .016). The association between statin use and PFS did not reach statistical significance (34.7 vs 9.9 months, P = .159). Multivariate Cox regression analysis showed that better performance status (hormone receptor [HR]: 0.30, 95% CI: 0.13-0.71, P = .006), use of trastuzumab plus pertuzumab prior to T-DM1 (HR: 0.37, 95% CI: 0.18-0.76, P = .007) and use of statins with T-DM1 (HR: 0.29, 95% CI: 0.12-0.70, P = .006) were independent factors that prolong OS duration. Our study showed that T-DM1 is more effective at treating HER2-positive breast cancer in people who receive statins concurrently with T-DM1 than those who do not.

Optimal adjuvant treatment strategies for TNBC patients with residual disease after neoadjuvant treatment.

INTRODUCTION: The therapeutic armamentarium for the neoadjuvant treatment of triple-negative breast cancer (TNBC) has significantly expanded with the hopes of improving pathological complete response (pCR) rates and the possibility of a cure. However, the data on optimal adjuvant treatment strategies for patients with residual disease after neoadjuvant treatment is limited. AREAS COVERED: We discuss the available data on adjuvant treatment for residual TNBC after neoadjuvant treatment considering clinical trials. Additionally, we discuss ongoing trials to give perspectives on how the field may evolve in the next decade. EXPERT OPINION: The available data support the use of adjuvant capecitabine for all patients and either adjuvant capecitabine or olaparib for patients with germline BRCA1 and BRCA2 mutations, according to availability. The CREATE-X study of capecitabine and OlympiA study of olaparib demonstrated disease-free and overall survival benefits. There is an unmet need for studies comparing these two options for patients with germline BRCA mutations. Further research is needed to delineate the use of immunotherapy in the adjuvant setting, molecular targeted therapy for patients with molecular alterations other than germline BRCA mutation, combinations, and antibody-drug conjugates to further improve outcomes.

Knowledge and Protective Behaviors of Teachers on Skin Cancer: A Cross-Sectional Survey Study from Turkey.

BACKGROUND: People socialize and receive education and training for the first time outside the home at school, where their teachers act as role models. Teachers play a crucial role in instilling sun-protection habits in children. Avoiding the sun between 10 a.m. and 4 p.m., staying in the shade, wearing sun-protective clothing, wearing sunglasses, wearing hats, using sunscreen products, and using an umbrella are some of the sun-protection methods described in the literature. This study sought to assess teachers' skin cancer knowledge and attitudes (SC). METHODS: In this cross-sectional study conducted between 21 September 2020, and 21 October 2020, 647 teachers from 30 schools in Kahramanmaras were included with their consent. The number of teachers employed at Kahramanmaras was 1863. Accordingly, the sample was found to be 641 with a 5% margin of error and a 99% confidence interval. Schools were selected by a simple random method. Teachers' knowledge and behaviors were assessed using a 25-point questionnaire designed by the literature data to gauge the level of SC knowledge. RESULTS: Of the 647 teachers included in this study, 230 (35.5%) were male, and 417 (64.5%) were female. The mean age of the participants was 38.44 ± 8.79 (min = 22, max = 65) years. The knowledge level of the teachers about SC was 13.54 ± 4.48 (min = 0, max = 23). The internet (75.9%) was the most preferred source of information. SC knowledge level was significantly higher in those with SC in their families and birthmarks on their bodies. (p < 0.001, p = 0.042, respectively). The rate of precaution taken to protect from the sun was higher in those with higher knowledge (p = 0.032). Women, primary school teachers, those with skin type 1, those with multiple nevi, and those with a high level of SC knowledge used statistically significantly more sunscreen (p = 0.001, p = 0.003, p < 0.001, p = 0.037, p = 0.002, respectively). CONCLUSIONS: It was found that the knowledge level of teachers about skin cancer and sun-protective behaviors was moderate. Correct behaviors increased as knowledge about SC grew. Information and recommendations made on the Internet should be made by experts. Additionally, health policymakers should implement projects aimed at improving teachers' knowledge and behaviors and, through them, teaching students about SC; as such projects would significantly contribute to both public health and health economics.

Emerging treatment strategies in hepatobiliary cancer.

INTRODUCTION: There have been significant advances in the treatment of hepatobiliary cancers, especially for advanced-stage disease. However, data is limited for optimal therapy selection in the first line and sequencing of available options. AREAS COVERED: This review covers the systemic treatment of hepatobiliary cancers with an emphasis on the advanced stage. The previously published and ongoing trials will be discussed to create an algorithm for the current practice and to give future perspectives on how the field could go forward. EXPERT OPINION: While there is no standard-of-care option in the adjuvant treatment of hepatocellular cancer, capecitabine is the standard of care for biliary tract cancer. The efficacy of adjuvant gemcitabine and cisplatin and the added benefit of radiotherapy to chemotherapy are yet to be defined. For the advanced stage, immunotherapy-based combinations became the standard of care for both hepatocellular and biliary tract cancers. The molecularly targeted therapy has profoundly changed the second-line and later treatment for biliary tract cancers, while the optimal second-line treatment for advanced hepatocellular cancer is yet to be defined due to rapid advances in the first-line setting.