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Background: Although higher-generation TKIs are associated with improved progression-free survival in advanced NSCLC patients with EGFR mutations, the optimal selection of TKI treatment remains uncertain. To address this gap, we developed a web application powered by a reinforcement learning (RL) algorithm to assist in guiding initial TKI treatment decisions., Methods: Clinical and mutational data from advanced NSCLC patients were retrospectively collected from 14 medical centers. Only patients with complete data and sufficient follow-up were included. Multiple supervised machine learning models were tested, with the Extra Trees Classifier (ETC) identified as the most effective for predicting progression-free survival. Feature importance scores were calculated by the ETC, and features were then integrated into a Deep Q-Network (DQN) RL algorithm. The RL model was designed to select optimal TKI generation and a treatment line for each patient and was embedded into an open-source web application for experimental clinical use., Results: In total, 318 cases of EGFR-mutant advanced NSCLC were analyzed, with a median patient age of 63. A total of 52.2% of patients were female, and 83.3% had ECOG scores of 0 or 1. The top three most influential features identified were neutrophil-to-lymphocyte ratio (log-transformed), age (log-transformed), and the treatment line of TKI administration, as tested by the ETC algorithm, with an area under curve (AUC) value of 0.73, whereas the DQN RL algorithm achieved a higher AUC value of 0.80, assigning distinct Q-values across four TKI treatment categories. This supports the decision-making process in the web-based 'EGFR Mutant NSCLC Treatment Advisory System', where clinicians can input patient-specific data to receive tailored recommendations., Conclusions: The RL-based web application shows promise in assisting TKI treatment selection for EGFR-mutant advanced NSCLC patients, underscoring the potential for reinforcement learning to enhance decision-making in oncology care.

Background and Aims: During liver transplantation, hepatocellular carcinoma (HCC) recurrence remains a critical challenge for patient survival. Targeted therapies, such as sorafenib and regorafenib, have been utilized to manage relapsed HCC in this unique setting. This study aimed to assess the efficacy of Sorafenib and Regorafenib in patients with HCC who experienced recurrence after liver transplantation. We focused on survival outcomes, treatment responses, and the management of side effects in this patient group., Methods: We conducted a retrospective analysis of 73 patients who experienced HCC recurrence post-liver transplantation between 2012 and 2022 across 11 oncology centers in Turkey. Patients were categorized according to Child-Pugh classification and treated with sorafenib as first-line therapy and Regorafenib in case of progression. Survival rates were analyzed using the Kaplan-Meier method, and risk factors were evaluated using Cox regression analysis., Results: Of the 73 patients included in the study, 62 were male (84.9%), and 11 were female (15.1%), with a mean age of 61.5 ± 10.9 years. All patients received sorafenib as first-line treatment. Among patients who experienced progression with sorafenib or discontinued treatment due to toxicity, 45.2% ( n = 33) continued treatment with regorafenib. The median progression-free survival (PFS1) time with sorafenib was 5.6 months, and the one-year survival rate was 24.3%. The median progression-free survival (PFS2) time with regorafenib, which was administered as second-line treatment, was also calculated as 5.9 months. Overall survival (OS) duration was determined as 35.9 months. The most common side effects associated with both drugs included fatigue, hand and foot syndrome, and hypertension. Significantly better survival outcomes were shown in the Child-Pugh A group compared to other patients., Conclusions: These results suggest that Sorafenib and Regorafenib treatments offer a survival advantage in patients with relapsed HCC post-transplantation. However, individualized treatment strategies and close follow-up are crucial for optimizing outcomes. Further studies are needed to refine therapeutic protocols and enhance the care of this specific patient group.

Aim: Endocrine therapy (ET) plus cyclin-dependent kinase (CDK) 4/6 inhibitors is a standard treatment for hormone receptor (HR) positive HER-2-negative metastatic breast cancer patients. In this study, we aimed to investigate the effect of body mass index (BMI) on progression-free survival (PFS) in patients receiving ET plus CDK 4/6 inhibitors. Materials & methods: Patients with metastatic HR-positive breast cancer receiving CDK 4/6 inhibitors were included in the study. A total of 116 patients were retrospectively evaluated. Patients were divided into three groups according to BMI level: normal weight (group 1) 18.5-24.9 kg/m 2 , overweight (group 2) 25-29.9 kg/m 2 and obese (group 3): ≥30 kg/m 2 . Median follow-up was 10.83 months. Comparisons of PFS and BMI categories were performed by Kaplan-Meier curve and log-rank test. Results: PFS was 9.3 (5.3-13.4) months in normal weight patients and 11.1 (9.7-12.56) months in obese patients and was not reached in overweight patients. This difference was statistically significant ( p  = 0.02). Conclusion: Low BMI has been shown to have a negative prognostic effect on survival in patients with metastatic breast cancer and overweight patients had a longer PFS.

Purpose: Anaplastic lymphoma kinase (ALK) mutations occurs in approximately 3-5% of patients with non-small cell lung cancer (NSCLC). Pleural involvement/effusion is common in ALK-positive patients with NSCLC at baseline. The aim of the study was to evaluate the characteristics of ALK-positive patients who have Ple-I/E., Methods: In this multicenter study, patients with ALK-positive NSCLC who have Ple-I/E were retrospectively analyzed. Clinical and demographic characteristics of the disease, response rates, median progression-free survival (PFS), and overall survival (OS) were evaluated in 362 ALK-positive patients with NSCLC., Results: Of the patients, 198 (54.7%) were male. The median age at the time of diagnosis was 54 (range 21-85) years. All patients' histology was adenocarcinoma (100%). At baseline, 57 (15.7%) patients had Ple-I/E. There was no association between Ple-I/E and gender, lung metastasis, or distant lymphadenopathy (LAP) metastasis. The frequencies of liver, brain, and bone metastases were significantly higher in ALK-positive patients without Ple-I/E compared to those with Ple-I/E (respectively 18.2% vs 4.8%, p = 0.008; 19.1% vs 4.8%, p = 0.001; 20.6% vs 8.9%, p = 0.002). The median PFS was longer in ALK-positive patients who had Ple-I/E (18.7 vs 10.6 months, p = 0.017). Similarly, the median OS was longer in ALK-positive patients who had Ple-I/E (44.6 vs 22.6 months, p = 0.051)., Conclusion: Brain, liver, and bone metastases were lower in ALK-positive patients with Ple-I/E. Patients presented with Ple-I/E were prone to have better PFS and OS., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This study aims to report the efficacy and safety of capecitabine plus temozolomide (CAPTEM) across different lines of treatment in patients with metastatic neuroendocrine tumors (NETs)., Methods: We conducted a multicenter retrospective study analyzing the data of 308 patients with metastatic NETs treated with CAPTEM between 2010 and 2022 in 34 different hospitals across various regions of Turkey., Results: The median follow-up time was 41.0 months (range: 1.7-212.1), and the median age was 53 years (range: 22-79). Our results across the entire patient cohort showed a median progression-free survival (PFS) of 10.6 months and a median overall survival (OS) of 60.4 months. First-line CAPTEM treatment appeared more effective, with a median PFS of 16.1 months and a median OS of 105.8 months (median PFS 16.1, 7.9, and 9.6 months in first-, second- and ≥third-line respectively, P = .01; with median OS values of 105.8, 47.2, and 24.1 months, respectively, P = .003) In terms of ORR, the first-line treatment again performed better, resulting in an ORR of 54.7% compared to 33.3% and 30.0% in the second and third or higher lines, respectively (P < .001). Grade 3-4 side effects occurred only in 22.5% of the patients, leading to a discontinuation rate of 9.5%. Despite the differences in outcomes based on treatment line, we did not observe a significant difference in terms of side effects between the first and subsequent lines of treatment., Conclusions and Relevance: The substantial superior outcomes in patients receiving first-line CAPTEM treatment highlight its potential as an effective treatment strategy for patients with metastatic NET., (© The Author(s) 2023. Published by Oxford University Press.)

Aim: We aimed to evaluate the effect of concomitant proton pump inhibitors (PPI) use with nivolumab on survival outcomes in metastatic renal cell carcinoma (mRCC) in second-line setting., Methods: The study was designed as a multicenter and retrospective involving patients with metastatic renal cell carcinoma receiving second-line nivolumab therapy. One hundred and nine patients with mRCC were divided into two groups based on whether they use PPI concomitantly with nivolumab: concomitant PPI users and non-users. Overall survival (OS) and progression-free survival (PFS) were compared between the groups with and without concurrent PPIs., Results: Of 109 patients in our study, 59 were not using PPI concomitantly with nivolumab and 50 were using PPI concomitantly. The median PFS was 6.37 (5.2-7.5) months in the concomitant PPI group and 9.7 (4.5-15) months in the non-users (p = 0.03). The median OS was 14.6 (7.1-22.1) months in patients on PPI concurrently with nivolumab and 29.9 (17.1-42.7) months in the non-users (p = 0.01). Accordingly, PPI use for PFS (Non-use vs. Use = HR: 0.44, 95%Cl 0.28-0.96, p = 0.014) and PPI use for OS (Non-use vs. Use = HR: 0.68, 95%Cl 0.22-0.88, p = 0.01) were found to be as independent risk factors., Conclusions: Concomitant use of PPIs is associated with worse survival outcomes in patients with mRCC treated with nivolumab. Clinicians should carefully consider the concomitant use of PPIs in such patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Alectinib is an effective second-generation ALK tyrosine kinase inhibitor (TKI) used in the first-line treatment of patients with advanced ALK-positive NSCLC. Recent studies demonstrated that the percentage of ALK-positive tumor cells in patient groups receiving crizotinib might affect outcomes. This study aimed to investigate whether the percentage of ALK-positive cells had a predictive effect in patients with advanced NSCLC who received first-line Alectinib as ALK-TKI., Materials and Methods: This retrospective study included patients with advanced-stage NSCLC who received alectinib as a first-line ALK-TKI and whose percentage of ALK-positive cells was determined by FISH at 27 different centers. Patients who received any ALK-TKI before alectinib were not included in the study. Patients were separated into two groups according to the median (40%) value of the percentage of ALK-positive cells (high-positive group ≥ 40% and low-positive group < 40%). The primary endpoint was PFS, and the secondary endpoints were OS, ORR, and PFS of the subgroups based on different threshold values for the percentage of ALK-positive cells., Results: 211 patients were enrolled (48.3% female, 51.7% male) to study. 37% (n = 78) of the patients had received chemotherapy previously. After a median of 19.4 months of follow-up, the median PFS was not reached in the high-positive group (n = 113), but it was 10.8 months in the low-positive group (n = 98) (HR 0.39; 95% CI 0.25-0.60, p < 0.001). The median OS in the high-positive group was not reached, whereas it was 22.8 months in the low-positive group (HR 0.37; 95% CI 0.22-0.63, p < 0.001). ORR was significantly higher in the high-positive group (87.2 vs. 68.5%; p = 0.002). According to the cut-off values of < 20%, 20-39%, 40-59%, and ≥ 60%, the median PFS was 4.5, 17.1, and 26 months, respectively, and could not be reached in the ≥ 60% group., Conclusion: Our study demonstrated that the efficacy of alectinib varies significantly across patient subgroups with different percentages of ALK-positive cells. If these findings are prospectively validated, the percentage of ALK-positive cells may be used as a stratification factor in randomized trials comparing different ALK-TKIs., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To evaluate the difference of progression free survival between the patients using concomitant proton pump inhibitors and non-users in the patients using CDK 4/6 inhibitors with HR + and HER2 negative mBC., Methods: We included 86 patients with HR + and HER 2 negative mBC treated with CDK 4/6 inhibitors in this study. Patients were divided into two categories according to their status of PPI use. The primary end points was progression free survival (PFS). We compared PPI users and non-users., Results: Forty-five (52.3%) patients used a PPI concomitantly with a CDK 4/6 inhibitor, and 41 (47.7%) did not. The median duration of follow-up was 10.68 (1.94-27.56) months. Of the patients, 50 (58.1%) palbociclib and 36 (41.9%) received ribociclib. The median progression free survival (mPFS) was 10.9 months (95% CI: 7.5-14.27) in the group with concomitant PPI use with a CDK 4/6 inhibitor, whereas the median progression free survival could not be reached in the group without concomitant PPI use (p = 0.04). In addition, concomitant PPI use with palbociclib was associated with a shorter PFS; there was no significant difference between the concomitant PPI users and non-users in terms of PFS in the patients using ribociclib., Conclusion: Palbociclib and ribociclib are weak base drugs so their bioavailability is pH-dependent. PPIs can affect their solubility and their concentration in the plasma. Therefore, we must avoid concomitant use of PPIs and CDK 4/6 inhibitors. If we need to use concomitant PPI and CDK 4/6 inhibitors, we should prefer ribociclib than palbociclib., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Atezolizumab has been shown to be effective and safe in randomized trial in the first-line treatment of extensive-stage small cell lung cancer (SCLC). However, there are limited real-life data on atezolizumab. In this study, we aimed to determine the real-life efficacy and safety of atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage SCLC., Methods: This trial is a retrospective multicenter study of the Turkish Oncology Group, which included extensive-stage SCLC patients who received atezolizumab combined with chemotherapy in a first-line treatment. The characteristics of the patients, treatment and response rates, and PFS and OS are presented. Factors associated with PFS and OS were analyzed by univariate and multivariate analysis., Results: A total of 213 patients at the 30 oncology centers were included. The median number of chemotherapy cycle was 5 (1-8) and atezolizumab cycle was 7 (1-32). After median 11.9 months of follow-up, median PFS and OS was 6.8 months (95%CI 5.7-7.8), and 11.9 months (95%CI 11-12.7), respectively. The ORR was 61.9%. ECOG-PS (p = 0.002) and number of metastatic sites (p = 0.001) were associated with PFS and pack-year of smoking (p = 0.05), while ECOG-PS (p = 0.03) and number of metastatic sites (p = 0.001) were associated with OS. Hematological side effects were common and toxicities were manageable., Conclusion: This real-life data confirm the efficacy and safety of atezolizumab in combination with chemotherapy in first-line treatment of extensive-stage SCLC., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: In this multicenter study, the authors aimed to determine the real-life efficacy and safety of first-line alectinib. Materials & methods: This retrospective trial included advanced-stage, ALK-positive non-small-cell lung cancer patients who were treated with first-line alectinib in terms of ALK-tyrosine kinase inhibitors, regardless of previous chemotherapy. The co-primary end points were progression-free survival both for all patients and for the treatment-naive population. The secondary end points were overall response rate, overall survival, rate of CNS progression and safety. Results & conclusion: A total of 274 patients (n = 177 for treatment-naive patients) were enrolled in the study. The median progression-free survival was 26 and 28.8 months for all patients and the treatment-naive group, respectively. The overall response rate, CNS progression rate and 1-year overall survival ratio were 77.9, 12.4 and 77%. Alectinib is a highly effective therapy with a favorable safety profile.

Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation., Materials and Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety., Results: Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients., Conclusion: Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: In this study, we looked for whether treatment-induced rash predicts treatment efficacy in patients with recurrent/metastatic HNSCC treated with Cetuximab and chemotherapy., Methods: Patients who were treated with platinum-based chemotherapy and cetuximab for the first line treatment of recurrent/metastatic HNSCC were recruited. Presence of rash, hypomagnesemia, hypopotassemia, anemia, neutropenia, thrombocytopenia during treatment and treatment response, date of progression, date of last visit and death were recorded., Results: A total of 138 patients' data were available for analysis. Any grade of rash was detected in 57 (44.5%) of the patients. The incidence of rash was significantly higher in patients with objective response than in patients with disease progression (%56.8 vs %14.3, p < 0.001). Progression free survival was 7.06 months (4.98-9.15) in patients treated with cetuximab and chemotherapy as first line treatment. In the multivariate analysis; rash was significantly correlated with longer PFS (HR 2.136; 95% CI 1.067-4.278; p = 0.032). Progression free survival was 9.65 months in patients who experienced rash, and 6.02 months in patients without rash, (p = 0.019, log-rank test). Overall survival was 11.24 months (9.65-12.82). In multivariate analysis, the survival of patients with rash was significantly longer than patients without rash (HR 1.954; 95% CI 1.162-3.285; p = 0.012). Overall survival was 15.08 months in patients who experienced rash, and 8.61 months in patients without rash (p = 0.05, log-rank test)., Conclusion: Cetuximab-induced rash is associated with better ORR and longer PFS and OS in patients with recurrent/metastatic HNSCC treated with Cetuximab and platinum-based chemotherapy., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: To assess the efficacy and tolerability of the first-line treatment options for hormone-refractory prostate cancer patients with visceral metastases. Materials & methods: The records of 191 patients diagnosed with hormone-refractory prostate cancer with visceral metastases were analyzed retrospectively. Results: Docetaxel was administered to 61.2% (n = 117), abiraterone to 14.2% (n = 27) and enzalutamide to 9.4% (n = 18) as the first-line treatment. The median survival of the patients receiving docetaxel, abiraterone and enzalutamide as the first-line treatment during the hormone-refractory period was 15 (95% Cl: 12.9-17) months, 6 (95% Cl: 1.8-10.1) months and 11 (95% Cl: 0.9-23.1) months (p = 0.038), respectively. Conclusion: The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival.

The updated version of Table 4 of original publication and the Compliance with ethical standards are given in this correction.

Background: Testicular cancer is a rare type of cancer in males. Since the disease is seen in young men and long-term survival is ensured following a high treatment success rate, fertility in testicular cancer patients is much more important. Prior to commencement of cancer treatment, patients are given counselling with regard to infertility and sexual function, and sperm banking is commonly carried out. The aim of this study was to assess the fertility status prior to and following treatment of monitored testicular cancer patients whose treatment had been completed., Methods: 110 patients diagnosed with and treated for testicular cancer at the Medical Oncology Clinic at Akdeniz University during the years 2000-2016 were evaluated for the study. The patients' disease and treatment information was obtained from their records. The patients' characteristics and fertility statuses were determined by means of interviews with the patients., Results: The median age of the patients was 36 (20-73) and 39.1% of them (n = 43) were aged between 30 and 39. The average length of follow-up was 6.20 ± 3.36 (2-17) years. It was determined that 42.7% of the patients had banked sperm following diagnosis and that 74.5% of them had received counselling. Following treatment, 33 patients (30%) fathered children. The average time taken to father children after treatment was 3 years., Conclusion: In testicular cancer patients, fatherhood is achieved spontaneously or with the cryopreservation process. Counselling plays an important role at the time of diagnosis. It is essential that health professionals in oncology clinics give counselling about fertility in testicular cancer.

Purpose: In this study our aim was to compare efficacy and toxicity profiles of two different schedule of carboplatin-paclitaxel regimen in elderly advanced non-small cell lung cancer (NSCLC) patients., Methods: Data from the charts of 59 elderly patients with metastatic NSCLC, treated with weekly paclitaxel combined with two different schedule of carboplatin were collected retrospectively from three medical oncology centers in Turkey between September 2002 to March 2018. No prior systemic therapy or radiotherapy was allowed. Brain metastases were not considered as exclusion criteria unless symptomatic. Patients were analyzed in two treatment groups; CP3 (who received 3 weekly carboplatin and weekly paclitaxel), and CP1 (weekly carboplatin and weekly paclitaxel). Overall survival (OS) was the primary endpoint of the study. Secondary end points were as follows: progression free survival (PFS), response rates (RR), grade 3-4 toxicities, skipped cycles, dose reductions, and treatment discontinuation rates., Results: Twenty-four patients received 3 weekly carboplatin and weekly paclitaxel schedule (CP3) while weekly carboplatin and weekly paclitaxel schedule (CP1) was performed in 35 patients. CP3 had a median OS of 14 months whereas CP1 had 9 months of median OS (p = 0.084). Both treatments (CP3 vs CP1) had similar median PFS (7 months vs 4 months, p = 0.109) and objective RR (20.9% vs 29.4%, p = 0.465). There was an increased incidence of grade 3-4 anemia and grade 3-4 neutropenia in CP3 compared to CP1 (p = 0.003 in both), but no major differences in febrile neutropenia and infection toxicity profiles (p = 0.289 and p = 0.770, respectively). Weekly schedule (CP1) had a tendency of increased grade 3-4 neurotoxicity (33.3% vs 42.9%, p = 0.461)., Conclusion: Weekly carboplatin and paclitaxel might be more tolerable and is as effective as 3 weekly carboplatin and weekly paclitaxel schedule in metastatic elderly NSCLC patients.

Gastric cancer, with one million new cases observed annually, and its dismal prognosis, is one of the leading causes of cancer-related mortalities. Systemic chemotherapy is the main treatment modality in advanced gastric cancer patients. We aim to evaluate the predictive role of tumor localization and histopathology on choosing three or two-drug combination regimens. Consecutive 110 metastatic gastric adenocarcinoma patients who were admitted to the Baskent University Department of Medical Oncology and the Van Research and Training Hospital were included in the study. Data of patients were analyzed retrospectively. Median age of patients was 58 years (range 30-80). Proximal intestinal, distal intestinal, and diffuse gastric cancers were found in 35 (32 %), 64 (58 %), and 11 (10 %) patients, respectively. 5-fluoracil and platinum (PF) and PFtax were administered to 47 (43 %) and 63 (57 %) patients, respectively. Median progression-free survival (PFS) was 4.0 (95 % CI 2.5-5.6) and 7.4 months (95 % CI 6.0-8.7) for PF and PFtax groups, (p = 0.034). When we used tumor localization as strata in the PFS survival curve, PFtax produced significantly higher PFS rates only in distal intestinal-type gastric cancer, compared with PF (p = 0.03). Median overall survival (OS) was 9.0 (95 % CI 5.2-12.3) and 17.3 months (95 % CI 7.8-27) for PF and PFtax groups, (p = 0.010). When we used tumor localization as strata in the OS survival curve, PFtax produced significantly higher OS rates only in distal intestinal-type gastric cancer compared with PF (p = 0.015). Pathology and tumor location in gastric cancers may affect the outcome, the addition of taxanes as a third drug may significantly increase PFS and OS rate purely in distal intestinal-type gastric cancer but not in patients with proximal and diffuse-type gastric cancers.

Background: An increasing number of patients receive palliative chemotherapy near the end of life. The aim of this study is to evaluate the aggressiveness of chemotherapy in Turkish individuals near the end of life., Methods: Patients diagnosed with solid tumors and died from 2010 to 2011 in the medical oncology department of Akdeniz University were included in the study. Data about the diagnosis, treatment details and imaging procedures were collected., Results: Three hundred and seventy-three people with stage IV solid tumors died from 2010 to 2011 in our clinic. Eighty-nine patients (23.9%) patients underwent chemotherapy in the last month of life while 39 patients (10.5%) received chemotherapy in the last 14 days. The probability of undergoing chemotherapy in the last month of life was influenced by: age, 'newly diagnosed' patients, and performance status. There was no significant association of chemotherapy in the last month of life with gender and tumor type. Having a PET-CT scan did not alter the chemotherapy decision., Conclusion: In conclusion, chemotherapy used in the last month of life in a tertiary care center of Turkey is high. Increasing quality of life should be a priority near the end of life and physicians should consider ceasing chemotherapy and direct the patient to early palliative care.

Bevacizumab is a humanized monoclonal antibody that inhibits vascular endothelial growth factor, and it has been found to increase both progression-free survival and overall survival when it is combined with chemotherapeutic agents in the first-line and subsequent treatment of metastatic colorectal carcinoma. The objective of this study was to show the efficacy of maintenance treatment with capecitabine plus bevacizumab in patients with metastatic colorectal cancer who responded to treatment with FOLFIRI plus bevacizumab. The study included patients with metastatic colorectal cancer who received FOLFIRI plus bevacizumab as a first-line treatment. Patients who had objective response with FOLFIRI plus bevacizumab treatment after an average period of 6 months received a maintenance treatment with capecitabine plus bevacizumab (capecitabine 2 x 1000 mg/m(2), 1 - 14 days, every 21 days, bevacizumab 7.5 mg/m(2), every 21 days) until disease progression or toxicity. The time to progression on bevacizumab treatment was evaluated. A total of 29 patients (15 male, 14 female) were included. The mean age was 62 years. The mean number of cycles for maintenance treatment with capecitabine plus bevacizumab was 12. The median PFS was 16 ± 3 months, and OS was 42 ± 11 months. PFS and OS were remarkably higher in patients with a complete or near complete response to induction treatment. Fourteen patients (48%) experienced hand-foot syndrome associated with capecitabine plus bevacizumab treatment, without any severe toxicity. Inselected patients with metastatic colorectal carcinoma who had a remarkable objective response to FOLFIRI plus bevacizumab treatment, a maintenance treatment with capecitabine plus bevacizumab following FOLFIRI plus bevacizumab until disease progression may be a suitable, effective and tolerable regimen, which requires further studies.

Background: Type 1 diabetes mellitus (DM) is an autoimmune disease with chronic complications that is becoming more frequent as life expectancy of diabetics has increased owing to improved methods of detection and better management. In this study, we investigated whether the presence of autoimmunity can be used in predicting the development time of microvascular complications., Material and Methods: Our study included 52 patients with type 1 diabetes mellitus (DM). The subjects had developed microvascular complications and they had been tested for anti-GAD (glutamic acid decarboxylase) antibodies and/or islet-cell antibodies (ICA). In the assessment of microvascular complications, we used ocular fundus examination, electromyography (EMG), and 24-h urine microalbuminuria tests., Results: Of the patients included in the study, 30 were female and 22 were male. Of all patients characterized for the existence of diabetic complications, 36 of 52 had both diabetic retinopathy and diabetic nephropathy, 5 patients had diabetic neuropathy, and 11 patients had diabetic retinopathy only. At the diagnosis of diabetes, 20 in 52 patients tested negative for autoantibodies (anti-GAD and anti-ICA), while 32 of 52 tested positive for anti-GAD and/or anti-ICA. The mean HbA1C level of autoantibody-negative patients was 7.7%, while antibody-positive patients had slightly higher HbA1c levels (7.9%). However, this difference was not statistically significant (p>0.05). The mean development time of microvascular complications in autoantibody-positive patients was calculated as 11: 40±6.46 years, and in patients with negative autoimmunity results it was 10.91±6.70 years., Conclusions: The presence of diabetes-related autoantibodies (DRAs) in patients with type 1 diabetes mellitus does not have a significant effect on the development time of diabetic microvascular complications.

Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM) and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2) is positive in gastric cancer at a rate of 7-34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG) involvement except bone metastases.

Introduction. Most common metastasis sites of breast cancer are the lungs, bones, liver, and brain, whereas uterine involvement by metastatic breast disease is rare. Metastatic carcinoma of the uterus usually originates from other genital sites, most commonly being from the ovaries. Invasive lobular carcinoma spreads to gynecologic organs more frequently than invasive ductal carcinoma. Case Report. A 57-year-old postmenopausal woman was diagnosed with breast carcinoma 2 years ago and modified radical mastectomy was performed. Pathological examination of tumor revealed invasive ductal carcinoma, stage IIIc. She presented with abdominal pain and distension. Diagnostic workup and gynecologic examination revealed lesions that caused diffuse thickening of the uterus wall. Endometrial sampling was performed for confirmation of the diagnosis. She underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Breast carcinoma metastases in endometrium and myometrium were confirmed histopathologically and immunohistochemically. Conclusion. We herein report the first case of isolated uterine patient who had invasive ductal carcinoma of breast.

Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal benign tumor which is generally seen in children and in young adults. It is especially located in the lungs. In histopathological examination, neoplastic fusiform cells originating from a subtype of accessory immune system cells which are called fibroblastic reticulum cells are seen (Kouichi and Youichirou, 2008). Although IMT is histopathologically benign, imaging methods show its tendency for local recurrence and invasion. In most of the cases, it may not be possible to make a distinction whether it is malign or benign. Complete surgical resection is the most important treatment method. In this study, we have discussed the findings of our case having a gastric submucosal located IMT in light of the current literatures.

Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient's history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

Background and Objectives: Numerous clinical concerns have been expressed regarding the potential worsening of cyclin-dependent kinase 4/6 inhibitor effects in breast cancer patients because of co-administration of proton pump inhibitors. Hence, this study evaluated the effects of proton pump inhibitors on the pharmacokinetics of palbociclib and ribociclib in terms of cytochrome P450 (CYP) 3A4 and P-glycoprotein involvement. Methods: The effects of omeprazole and rabeprazole on drug metabolism and efflux of these drugs were investigated using molecular docking, metabolic stability assay in rat liver microsomes, human recombinant CYP3A4 (rCYP3A4) enzymes, and Caco-2 cell monolayers, and in vivo pharmacokinetics with omeprazole and rabeprazole in (5 and 10 mg/kg) 30 min and 7 days before orally dosing palbociclib and ribociclib (10 mg/kg). Results: Omeprazole and rabeprazole inhibited CYP3A4 enzyme activity in rCYP3A4 baculosomes with a 50–60% inhibition at 30 μM. Additionally, both omeprazole and rabeprazole (10 µm) significantly reduced the P-glycoprotein-mediated drug efflux of palbociclib and ribociclib. The 7-day pretreatment of omeprazole at a dose of 10 mg/kg resulted in 24% and 26% reductions in palbociclib's mean maximum plasma concentration) Cmax and area under the plasma concentration–time curve (AUC0-24 h), respectively. Palbociclib's pharmacokinetics were not significantly altered by the pretreatment with rabeprazole; however, ribociclib pharmacokinetics exhibited an 83.94% increase in AUC0-24 h. Conclusion: The findings indicate that long-term treatment with therapeutic doses of both omeprazole and rabeprazole can alter the pharmacokinetics of palbociclib and ribociclib. The co-administration of rabeprazole may alter the pharmacokinetics of palbociclib and ribociclib via CYP enzyme and P-glycoprotein inhibition. [ABSTRACT FROM AUTHOR]

Introduction: Limited awareness exists regarding real-world data (RWD) for palbociclib in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced/metastatic breast cancer in populations from certain countries outside of Western regions. Methods: A systematic scoping review was conducted using PubMed and Embase to evaluate RWD for palbociclib from countries outside of Western regions that are underrepresented in clinical trials. Search criteria were aligned with our research question for relevant English-language publications, without restrictions on publication date, followed by Phase 1 (title and abstract) and Phase 2 (full-text) screening of retrieved citations as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data analyses of eligible studies were done separately for abstracts and full-text publications to enhance the precision and reliability of the results. Results: Database search yielded 1485 non-duplicate records, 46 qualified for inclusion, of which 47.8% were published as full text. The analysis of outcomes, based exclusively on full-text publications that collectively included 2048 patients treated with palbociclib, revealed the median progression-free survival (PFS) of 20.2–36.7 months, overall survival (OS) of 39.9 months (reported in one publication) and objective response rate (ORR) of 45.3–80.0% with first-line treatment. In ≥ second line, the median PFS, OS and ORR ranged from 7.0 to 24.2 months, 11 to 19.6 months, and 13.9% to 47.9%, respectively. The safety profile of palbociclib was similar to that reported in pivotal clinical studies, and no new safety concerns were identified. Conclusions: A comprehensive volume of evidence demonstrates that palbociclib's effectiveness and safety profile in real-world settings align with those observed in clinical trials, offering valuable insights for clinical decision-making in countries outside of Western regions underrepresented in clinical trials. [ABSTRACT FROM AUTHOR]

Palbociclib and ribociclib an orally bioavailable, potent cyclin-dependent kinase 4/6 inhibitors, with low oral bioavailability due to substrate specificity towards CYP3A and P-glycoprotein. Thus, current research aims to examine the effect of a bioenhancer (naringin), on oral pharmacokinetics of palbociclib and ribociclib. Naringin’s affinity for CYP3A4 and P-glycoprotein was studied using molecular docking; its impact on palbociclib/ribociclib CYP3A metabolism and P-glycoprotein-mediated efflux was examined using in vitro preclinical models; and its oral pharmacokinetics in rats were assessed following oral administration of palbociclib/ribociclib in presence of naringin (50 and 100 mg/kg). Naringin binds optimally to both proteins with the highest net binding energy of − 1477.23 and − 1607.47 kcal/mol, respectively. The microsomal intrinsic clearance of palbociclib and ribociclib was noticeably reduced by naringin (5–100 µM), by 3.0 and 2.46-folds, respectively. Similarly, naringin had considerable impact on the intestinal transport and efflux of both drugs. The pre-treatment with 100 mg/kg naringin increased significantly (p < 0.05) the oral exposure of palbociclib (2.0-fold) and ribociclib (1.95-fold). Naringin's concurrent administration of palbociclib and ribociclib increased their oral bioavailability due to its dual inhibitory effect on CYP3A4 and P-glycoprotein; thus, concurrent naringin administration may represent an innovative strategy for enhancing bioavailability of cyclin-dependent kinase inhibitors. [ABSTRACT FROM AUTHOR]

Background: Inflammatory myofibroblastic tumor (IMT) of the stomach is an uncommon mesenchymal neoplasm. We present a case of gastric submucosal tumor (SMT) where the final diagnosis was IMT. Case presentation: A 69-year-old man presented with a 24-mm SMT on the posterior wall of the middle third of the stomach that was detected by screening upper gastrointestinal endoscopy. Abdominal contrast-enhanced computed tomography showed that the tumor was well-enhanced. Although endoscopic ultrasonography-guided biopsy was performed, the histological diagnosis was not confirmed preoperatively. Since the tumor was clinically suspected to be a gastrointestinal stromal tumor, we performed gastric wedge resection by laparoscopic–endoscopic cooperative surgery. Pathologically, proliferative spindle cells with a positive reaction for smooth muscle actin, negativity for c-kit, desmin, s-100, CD34, STAT-6, β-catenin and anaplastic lymphoma kinase 1 were identified. Hence, the tumor was finally diagnosed as an IMT originating from the stomach. Conclusions: When an SMT of the stomach is identified, the possibility of gastric IMT should be considered. [ABSTRACT FROM AUTHOR]

Background: In industries worldwide, crystalline silica is pervasive and poses risks of pneumoconiosis and respiratory malignancies, with the latter being a knowledge gap in disease burden research that this study aims to address. By integrating both diseases, we also seek to provide an in-depth depiction of the silica-attributed disease burden. Methods: Data from the Global Burden of Disease 2019 were extracted to analyze the disease burden due to silica exposure. The trends of age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) from 1990 to 2019, as well as the age-specific number and rate of deaths and disability-adjusted life years (DALYs) in 1990 and 2019, were presented using GraphPad Prism software. The average annual percentage changes (AAPCs) on ASMR and ASDR were calculated using joinpoint regression models. Results: The global trends of disease burden due to silica exposure from 1990 to 2019 showed a significant decrease, with AAPCs on ASMR and ASDR of -1.22 (-1.38, -1.06) and − 1.18 (-1.30, -1.05), respectively. Vietnam was an exception with an unprecedented climb in ASMR and ASDR in general over the years. The age-specific deaths and DALYs mainly peaked in the age group 60–64. In comparison to 1990, the number of deaths and DALYs became higher after 45 years old in 2019, while their rates stayed consistently lower in 2019. Males experienced an elevated age-specific burden than females. China’s general age-standardized burden of pneumoconiosis and tracheal, bronchus & lung (TBL) cancer ranked at the forefront, along with the highest burden of pneumoconiosis in Chilean males and South African females, as well as the prominent burden of TBL cancer in Turkish males, Thai females, and overall Vietnamese. The age-specific burden of TBL cancer surpassed that of pneumoconiosis, and a delay was presented in the pneumoconiosis pinnacle burden compared to the TBL cancer. Besides, the burden of pneumoconiosis indicated a sluggish growth trend with advancing age. Conclusion: Our research highlights the cruciality of continuous enhancements in occupational health legislation for countries seriously suffering from industrial silica pollution and the necessity of prioritizing preventive measures for male workers and elderly retirees. [ABSTRACT FROM AUTHOR]

Background: Inflammatory myofibroblastic tumor (IMT) is a rare stromal tumor, often found in children and young adults, and most commonly occurs in the lungs. Surgical resection is considered the standard treatment for localized IMT, although only limited data exist. Gastric IMT in adults is extremely rare, and there are no established guidelines for its treatment. Case presentation: A 69-year-old male presented with persistent fatigue and weakness. Laboratory examination revealed severe anemia and inflammation. Upper gastrointestinal endoscopy at admission revealed a 40-mm type I softish tumor in the lesser curvature of the gastric body, without apparent hemorrhage. Repeated biopsies, including partial resection with snare, failed to give a definitive diagnosis. Computed tomography (CT) revealed a massive lesion at the gastric body, protruding into the gastric lumen, which was consistent with the gastric tumor. After admission, the patient developed anemia refractory to frequent blood transfusions despite the absence of apparent gastrointestinal bleeding. In addition, the patient had recurrent fevers of 38 °C or higher, and persistent high inflammatory levels. Fluorodeoxyglucose-positron emission tomography (FDG-PET) CT 1 month after the first visit exhibited an increased FDG uptake in the gastric tumor. In addition, this CT scan revealed a rapid increase in tumor size to 75 mm. It was suspected that the undiagnosed gastric tumor caused these serious clinical symptoms, and he underwent distal gastrectomy and cholecystectomy. The gross image of the tumor showed an 80-mm cauliflower-like shape with a gelatinous texture. The histopathological diagnosis was IMT. The postoperative course was uneventful, and the patient's symptoms subsided drastically, improving both anemia and systemic inflammation. The patient has shown no recurrence or relapse of the symptoms over one and a half years. Conclusions: In this case, the tumor resection finally enabled the diagnosis of IMT and resolved the clinical symptoms. Despite its predominantly benign morphological nature, some cases of IMT present clinically adverse courses. Surgical treatment may lead to its final diagnosis and improvement of clinical symptoms. [ABSTRACT FROM AUTHOR]

STUDY QUESTION Does sperm cryopreservation serve as a feasible and effective method for preserving fertility in adult male patients with cancer? SUMMARY ANSWER Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. WHAT IS KNOWN ALREADY Sperm cryopreservation is the only way to efficiently preserve male fertility. It is an important procedure in ART. Recently, due to remarkable advances in cancer treatment, an increasing number of studies have reported the outcomes of sperm cryopreservation in patients with cancer. STUDY DESIGN, SIZE, DURATION We conducted an extensive literature search for relevant studies published through to 31 December 2021, in the following databases: CENTRAL, CNKI, Cochrane Systematic Reviews, EMBASE, MEDLINE, PUBMED, and Web of Science. The search terms used were '(cryopreservation OR freeze OR freezing OR banking OR cryostorage OR storage) AND (sperm OR semen OR spermatozoon) AND (cancer OR tumor OR malignancy OR neoplasm)'. PARTICIPANTS/MATERIALS, SETTING, METHODS We included all studies that reported offering or attempting to cryopreserve sperm before or during cancer treatment in male patients considered at risk of treatment-related fertility impairment. We evaluated the eligibility of all data in each study. The major exclusion criteria were as follows: non-cancer patients; pediatric and adolescent cancer patients; not reporting the use of cryopreserved sperm; use of fresh semen for ART; not reporting the number of patients with cancer offered sperm cryopreservation or attempting to do so before or during treatment; using an experimental fertility preservation technique such as preservation of testicular tissue or spermatogonial stem cells; duplicate data; abstracts, case report, comments, reviews, or editorials; insufficient data reported. The quality of the included studies was assessed using the Newcastle–Ottawa scale and the Methodological Index for Non-Randomized Studies. MAIN RESULTS AND THE ROLE OF CHANCE This meta-analysis included 69 non-randomized studies, with 32 234 patients referred for sperm analysis and 23 178 patients cryopreserving at least one sperm sample. The pooled failed-to-cryopreserve rate was 10% (95% CI, 8–12%), and the sperm disposal and sperm use rates were 23% (95% CI, 16–30%) and 9% (95% CI, 8–10%), respectively. The pregnancy, miscarriage, and delivery rates were 28% (95% CI, 22–33%), 13% (95% CI, 10–17%), and 20% (95% CI, 15–25%), respectively. Subgroup analysis showed higher pregnancy and delivery rates, as well as a lower failed-to-cryopreserve rate, in recent studies compared to those released a decade ago. The studies from Asia reported higher sperm disposal and pregnancy rates than in other continents. Our analysis showed clinical pregnancy rates per cycle of 34% (27–41%), 24% (14–35%), and 9% (5–15%) and delivery rates per cycle of 23% (17–30%), 18% (11–26%), and 5% (1–9%) for ICSI, IVF, and IUI, respectively. LIMITATIONS, REASONS FOR CAUTION As with all meta-analyses, some limitations should be considered. The first limitation of our study is that the data span 36 years. During this time, the World Health Organization has revised its sperm analysis standards, and other important changes have been made. There is also a limitation in that the outcome does not analyze the correlation between the type of cancer and sperm quality. Many of the earlier studies were limited by small sample sizes and a lack of control groups. Furthermore, almost all studies did not consider the severity of the disease, which could potentially have a substantial impact on the results. Consequently, further research should evaluate the effect of the type of cancer and, in particular, the severity of the condition on sperm quality in order to draw more precise conclusions. Similarly, it is inappropriate that most studies failed to differentiate between patients with different types of tumors and instead drew generalized conclusions that are presumed to apply to all patients with cancer. In the present analysis, we did not have in-depth information on patients' disease, and although extensive efforts were made to conduct a thorough systematic review and meta-analysis of the outcomes for patients with various types of tumors, the results must be acknowledged as being subject to bias. However, the use of average results obtained in each study, without the patient-level data, might also represent a source of bias. WIDER IMPLICATIONS OF THE FINDINGS Sperm cryopreservation is an effective fertility preservation method and may benefit patients with cancer. The observed utilization rate of frozen sperm at 9% may underestimate the actual usage, as the short follow-up period is inadequate for obtaining comprehensive data on the use of frozen sperm in young cancer survivors. ART plays an important role in fertility preservation and the achievement of pregnancy, with this meta-analysis showing that ICSI delivers better clinical outcomes than IVF or IUI in patients with cancer undergoing fertility preservation. STUDY FUNDING/COMPETING INTERESTS This work was supported by the National Natural Science Foundation of China (grant no. 82001634, 81960550), and the China Postdoctoral Science Foundation (2019M661521). There are no competing interests to declare. REGISTRATION NUMBER CRID 42022314460. [ABSTRACT FROM AUTHOR]

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Opinion Statement: Systemic anticancer therapy (SACT) includes different treatment modalities that can be effective in treating cancer. However, in the case of disease progression, cancers might become incurable and SACT might reach its limits. In the case of incurable cancers, SACT is often given in a palliative setting, with the goal of improving the patients' quality of life (QOL) and their survival. In contrast, especially for patients who approach end of life (EOL), such treatments might do more harm than good. Patients receiving EOL anticancer treatments often experience belated palliative care referrals. The use of systemic chemotherapy in patients with advanced cancer and poor prognosis approaching the EOL has been associated with significant toxicity and worse QOL compared to best supportive care. Therefore, the American Society of Clinical Oncology (ASCO) has discouraged this practice, and it is considered a metric of low-value care by Choosing Wisely (Schnipper et al. in J Clin Oncol 4;30(14):1715-24). Recommendations of the European Society for Medical Oncology (ESMO) suggest that especially chemotherapy and immunotherapy should be avoided in the last few weeks of the patients' lives. In this narrative review, we screened the current literature for the impact of SACT and factors predicting the use of SACT near the EOL with discussion on this topic. [ABSTRACT FROM AUTHOR]

Introduction: New agents are introduced each day to be used in the prevention and treatment of mucositis in cancer treatment. One of those agents is the Ankaferd hemostat. Ankaferd hemostat has pleiotropic effects and anti-infective characteristics in tissue healing. Methods: The study was designed as a randomized controlled experimental study. The sample of the study comprised a total of 66 patients (33 patients in the Ankaferd hemostat group and 33 patients in the sodium bicarbonate group) with colorectal cancer who received FOLFOX combination chemotherapy treatment in the first cycle of chemotherapy to prevent mucositis. Participants who met the criteria were randomly assigned to the groups. Before the patient received chemotherapy, ECOG performance score and Oral Mucositis Grading Scale were applied on the 7th day and 15th day. The Ankaferd hemostat group brushed teeth at least twice a day for 2 min and gargled with Ankaferd hemostat twice for 2 min for 2 weeks. The sodium bicarbonate group brushed teeth at least 2 min a day and gargled with sodium bicarbonate 4 times for 2 min for 2 weeks. The Consolidated Standards of Reporting Trials diagram was used to illustrate the randomization of patients. Results: When the Ankaferd hemostat group is compared with the sodium bicarbonate group, there is a significant difference in favor of the Ankaferd hemostat group in the mucositis grade on the 7th day and 15th day after chemotherapy (p < 0.05). In the binary logistic regression analysis, among the factors affecting the formation of mucositis on the 7th day, only neutrophil and thyroid-stimulating hormone (TSH) were included in the model, while only the TSH variable is statistically significant. Conclusions: It was determined that Ankaferd hemostat is effective in preventing oral mucositis due to chemotherapy in adult patients diagnosed with colorectal cancer. In addition, it has been suggested to conduct new studies on the effectiveness of Ankaferd hemostat in the prevention of mucositis in different groups. Trial registration: The study was registered at ClinicalTrials.gov (ID: NCT05438771, Date: 25.06.2022). [ABSTRACT FROM AUTHOR]

Lapatinib is used for the treatment of metastatic HER2(+) breast cancer. We aim to establish a prediction model for lapatinib dose using machine learning and deep learning techniques based on a real-world study. There were 149 breast cancer patients enrolled from July 2016 to June 2017 at Fudan University Shanghai Cancer Center. The sequential forward selection algorithm based on random forest was applied for variable selection. Twelve machine learning and deep learning algorithms were compared in terms of their predictive abilities (logistic regression, SVM, random forest, Adaboost, XGBoost, GBDT, LightGBM, CatBoost, TabNet, ANN, Super TML, and Wide&Deep). As a result, TabNet was chosen to construct the prediction model with the best performance (accuracy = 0.82 and AUC = 0.83). Afterward, four variables that strongly correlated with lapatinib dose were ranked via importance score as follows: treatment protocols, weight, number of chemotherapy treatments, and number of metastases. Finally, the confusion matrix was used to validate the model for a dose regimen of 1,250 mg lapatinib (precision = 81% and recall = 95%), and for a dose regimen of 1,000 mg lapatinib (precision = 87% and recall = 64%). To conclude, we established a deep learning model to predict lapatinib dose based on important influencing variables selected from real-world evidence, to achieve an optimal individualized dose regimen with good predictive performance. [ABSTRACT FROM AUTHOR]

Summary: Background: Eccrine porocarcinoma (EPC) is a rare skin cancer arising from the eccrine sweat glands. Due to the lack of effective therapies, metastasis is associated with a high mortality rate. Objectives: To investigate the drivers of EPC progression. Methods: We carried out genomic and transcriptomic profiling of metastatic EPC (mEPC), validation of the observed alterations in an EPC patient‐derived cell line, confirmation of relevant observations in a large patient cohort of 30 tumour tissues, and successful treatment of a patient with mEPC under the identified treatment regimens. Results: mEPC was characterized by a high tumour mutational burden (TMB) with an ultraviolet signature, widespread copy number alterations and gene expression changes that affected cancer‐relevant cellular processes such as cell cycle regulation and proliferation, including a pathogenic TP53 (tumour protein 53) mutation, a copy number deletion in the CDKN2A (cyclin dependent kinase inhibitor 2A) region and a CTNND1/PAK1 [catenin delta 1/p21 (RAC1) activated kinase 1] gene fusion. The overexpression of EGFR (epidermal growth factor receptor), PAK1 and MAP2K1 (mitogen‐activated protein kinase kinase 1; also known as MEK1) genes translated into strong protein expression and respective pathway activation in the tumour tissue. Furthermore, a patient‐derived cell line was sensitive to EGFR and MEK inhibition, confirming the functional relevance of the pathway activation. Immunohistochemistry analyses in a large patient cohort showed the relevance of the observed changes to the pathogenesis of EPC. Our results indicate that mEPC should respond to immune or kinase inhibitor therapy. Indeed, the advanced disease of our index patient was controlled by EGFR‐directed therapy and immune checkpoint inhibition for more than 2 years. Conclusions: Molecular profiling demonstrated high TMB and EGFR/MAPK pathway activation to be novel therapeutic targets in mEPC. Whatis already known about this topic?Eccrine porocarcinoma (EPC) is a rare skin cancer with a largely unknown aetiology and molecular makeup.In cases not amendable by surgery, no effective treatment is available. Whatdoes this study add?Using comprehensive genomic and transcriptomic profiling, aberrations in cancer‐relevant signalling pathways were identified that could not only be validated functionally in a newly established patient‐derived culture model but could also be confirmed in a larger series of retrospective cases.Importantly, these observations were translated into treatment regimens resulting in substantial clinical benefit in a patient with metastatic EPC. Whatis the translational message?Here, we provide an excellent example of how from‐bedside‐to‐bench and back can work.We not only detected relevant genetic aberrations in EPC, but also confirmed their functional relevance and their transferability to additional cases, culminating in effective treatment of the patient.We thus provide new therapeutic options for EPC and possibly other adnexal carcinomas with similar molecular makeup. Plain language summary available online [ABSTRACT FROM AUTHOR]

Background: HER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes. Methods: A total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS). Results: The median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%). Conclusion: Pyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib. [ABSTRACT FROM AUTHOR]

Background: Invasive lobular carcinoma and ductal carcinoma of the breast can metastasize to all sites in the body, including the gastrointestinal tract. Late presentation of metastases of lobular carcinoma of the breast to the gastrointestinal tract have previously been reported, but late metastasis of ductal carcinoma of the breast to the gastric mucosa is rare. This report is of a 58-year-old Lebanese woman who presented with acute gastric perforation due to metastatic ductal carcinoma, 18 years following bilateral mastectomy for invasive ductal carcinoma of the breast. Case Report: We present the case of a 58-year-old woman who underwent a right modified mastectomy for an invasive ductal carcinoma in 2002 combined with a contralateral prophylactic mastectomy for cosmetic purposes. She presented a secondary gastric lesion 18 years later. The clinical presentation resembled perforated ulcer. The choice of gastrectomy was denied due to retrogastric and pancreatic invasion by the tumor. A laparoscopic gastric closure failed to heal the perforation. A supraumbilical laparotomy incision was performed for the placement of a Pezzer tube in the gastric perforation and the installation of a feeding jejunostomy. Conclusions: This report is of a rare presentation of metastatic ductal carcinoma of the breast to the gastric mucosa associated with gastric perforation that presented 18 years after bilateral mastectomy. This case highlights the importance of obtaining a full past medical history to identify previous primary malignancy, and also is a reminder that ductal carcinoma of the breast can present with metastatic involvement in the gastrointestinal tract several months, or even years, following mastectomy. [ABSTRACT FROM AUTHOR]

Objective: In this study, we aimed to develop a candidate modifited polymeric nanoparticle (NP) system that will kill cancer cells by facilitated to apoptosis and also reduce pain. Significance: The primary goal of treatment, especially for metastatic cancers, is to control the growth of the cancer and to alleviate the symptoms. Pain is one of the commonest symptoms of cancer. In cancer treatment, directing cancer cells to death while simultaneously relieving pain will be a new approach. Methods: Chitosan-modified PLGA NPs were prepared using an nanoprecipitation technique. The NPs were loaded with flurbiprofen and decorated with folic acid. STAT3-siRNA was adsorbed to these polymeric NPs using antisense technology. Results: The NPs were small in size (176.9–220.3 nm) with positive zeta potential (+14.1 mV to +27.2 mV). They had high loading capacity and prolonged release properties over 144 hours. Cytotoxicity studies performed with siRNA showed effective electrostatic interaction due to the positively charged NPs. Folic acid facilitated entry into cancer cells and helped to kill them. Conclusion: The formulation we developed is a potential carrier system for both treatment of cancer and prevention of pain, especially for metastatic cancers. [ABSTRACT FROM AUTHOR]

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Patients with advanced cancer often continue to choose aggressive interventions and/or treatments up until the final stages of life. This clinical approach may compromise the preservation of a patient’s quality of life, and secondarily, contributes to higher healthcare costs. Therefore, the ethics of enrolling terminal cancer patients in clinical trials which are testing new, aggressive chemotherapy agents requires careful discussion between the Oncology and the Palliative Care team. We present the case of a patient with stomach cancer admitted to a clinical trial at a very advanced stage of her disease. A number of clinical and ethical difficulties encountered by the PC team are discussed as well as possible solutions. [ABSTRACT FROM PUBLISHER]

Purpose: The use of chemotherapy in the last month of life (CLML) of cancer patients is considered an aggressive approach to be avoided. We examined the practice of CLML in Lebanese cancer patients, and we investigated patient and tumor characteristics that justify this practice. To our knowledge, this is the first study describing CLML of Middle Eastern patients with advanced cancer.Methods: We conducted this study at Hotel-Dieu de France University Hospital (HDF), Lebanon. Cases eligible for this study were all individuals diagnosed with cancer who died at HDF between the 1st of January and the 31st of December 2014. Demographic and clinical characteristics of the patients were obtained from the hospital registration records. Data concerning the management plan, primary malignancy and stage, chemo-sensitivity, line, type, and timing of chemotherapy in the last month of life were also obtained.Results: Among the 130 cancer patients who were enrolled, CLML was administered to a total of 55 patients (42.3 %), of whom 26 patients (50 %) received more than one cytotoxic drug. Oral drug was only given to 9 patients (16.4 %). Interestingly, CLML increased the risk of death in the last month of life (p = 0.02), yet progression of disease constituted the major cause of death in this subgroup (54.6 %). The only variable to have statistical significant correlation with CLML was performance status (p = 0.03). The type of tumor and recent diagnosis of less than 2 months were also correlated to CLML (p = 0.03 and 0.024, respectively).Conclusion: The high percentage of patients receiving CLML underlines the difficulty of end-of-life discussions in patients from Middle Eastern societies. This is true in the context of a country with little availability of palliative care resources, where health policies should be more focused on incorporating palliative medicine in all medical strategies. [ABSTRACT FROM AUTHOR]

Advanced incurable cancer patients receive palliative chemotherapy to prolong their life and improve quality of life. However, physicians should assess the timing to discontinue the treatment, especially near the final months of life, as palliative chemotherapy may accompany considerable toxicity. Even though there are no clear guidelines regarding the withdrawal timing for anticancer treatment in palliative setting, it is important clarify the issue for quality of care for advanced cancer patients. Here, we present two patients who received palliative chemotherapy for advanced colon cancer and non-small cell lung cancer, respectively. In both cases, it was jointly determined to stop palliative chemotherapy, and best efforts are made to relieve troublesome symptoms. The cases and upto-date literature review will highlight the importance of the timing of discontinuation of cancer treatments when changes are being made to the health care system and hospice and palliative medicine is taking root in Korea. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Clinical & Experimental Investigations is the property of Modestum Publications and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)