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.

ChatGPT vs UpToDate: comparative study of usefulness and reliability of Chatbot in common clinical presentations of otorhinolaryngology-head and neck surgery.

PURPOSE: The usage of Chatbots as a kind of Artificial Intelligence in medicine is getting to increase in recent years. UpToDate® is another well-known search tool established on evidence-based knowledge and is used daily by doctors worldwide. In this study, we aimed to investigate the usefulness and reliability of ChatGPT compared to UpToDate in Otorhinolaryngology and Head and Neck Surgery (ORL-HNS). MATERIALS AND METHODS: ChatGPT-3.5 and UpToDate were interrogated for the management of 25 common clinical case scenarios (13 males/12 females) recruited from literature considering the daily observation at the Department of Otorhinolaryngology of Ege University Faculty of Medicine. Scientific references for the management were requested for each clinical case. The accuracy of the references in the ChatGPT answers was assessed on a 0-2 scale and the usefulness of the ChatGPT and UpToDate answers was assessed with 1-3 scores by reviewers. UpToDate and ChatGPT 3.5 responses were compared. RESULTS: ChatGPT did not give references in some questions in contrast to UpToDate. Information on the ChatGPT was limited to 2021. UpToDate supported the paper with subheadings, tables, figures, and algorithms. The mean accuracy score of references in ChatGPT answers was 0.25-weak/unrelated. The median (Q1-Q3) was 1.00 (1.25-2.00) for ChatGPT and 2.63 (2.75-3.00) for UpToDate, the difference was statistically significant (p < 0.001). UpToDate was observed more useful and reliable than ChatGPT. CONCLUSIONS: ChatGPT has the potential to support the physicians to find out the information but our results suggest that ChatGPT needs to be improved to increase the usefulness and reliability of medical evidence-based knowledge.

The real-world outcomes of Lutetium-177 PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer: Turkish Oncology Group multicenter study.

Metastatic castration-resistant prostate cancer (mCRPC) remains a challenging condition to treat despite recent advancements. This retrospective study aimed to assess the activity and tolerability of Lutetium-177 (Lu-177) PSMA-617 radioligand therapy (RLT) in mCRPC patients across multiple cancer centers in Turkey. The study included 165 patients who received at least one cycle of Lu-177 PSMA-617 RLT, with the majority having bone metastases and undergone prior treatments. Prostate-specific antigen (PSA) levels were assessed before each treatment cycle, and the biochemical response was evaluated in accordance with the Prostate Cancer Work Group 3 Criteria. The PSA decline of ≥50% was classified as a response, while an increase of ≥25% in PSA levels was indicative of progressive disease. Neither response nor progression was considered as stable disease. The Lu-177 PSMA-617 RLT led to a significant PSA response, with 50.6% of patients achieving a >50% decrease in PSA levels. Median overall survival (OS) and progression-free survival were 13.5 and 8.2 months, respectively. Patients receiving Lu-177 PSMA-617 RLT in combination with androgen receptor pathway inhibitors (ARPIs) had a higher OS compared to those receiving Lu-177 PSMA-617 RLT alone (18.2 vs 12.3 months, P = .265). The treatment was generally well-tolerated, with manageable side effects such as anemia and thrombocytopenia. This study provides real-world evidence supporting the effectiveness and safety of Lu-177 PSMA-617 RLT in mCRPC patients, particularly when used in combination with ARPIs. These findings contribute to the growing body of evidence on the potential benefits of PSMA-targeted therapies in advanced prostate cancer.

Survival outcomes and prognostic nutritional index in very elderly small-cell lung cancer patients: importance of active treatment and nutritional support.

BACKGROUND: Small-cell lung cancer (SCLC) is a highly aggressive tumor with a high metastatic potential, particularly affecting current or former heavy smokers. Treatment typically involves chemotherapy, often combined with radiotherapy, and immunotherapy for extensive disease. Prophylactic cranial irradiation is recommended to reduce brain metastases. Elderly SCLC patients face unique challenges due to frailty and comorbidities, leading to increased risks of treatment-related toxicity and malnutrition. The prognostic nutritional index (PNI), a composite marker of nutritional and immune status, has shown promise in predicting outcomes in various malignancies. However, the optimal treatment approach for very elderly SCLC patients remains unclear, as they are often excluded from clinical trials. AIMS: This study aimed to evaluate the survival outcomes of SCLC patients aged 75 years or older and their correlation with PNI. STUDY DESIGN: Retrospective cohort study. METHODS: The study retrospectively analyzed data from 71 SCLC patients aged ≥75 years, focusing on age, gender, smoking status, chronic diseases, performance status, clinical stage, treatment modality, and pretreatment PNI. Survival estimates were calculated using the Kaplan-Meier method, and multivariate Cox regression analysis was performed to identify independent predictors of overall survival (OS). RESULTS: The results demonstrated that 26.8% of very elderly SCLC patients received no active treatment, resulting in a significantly shorter median survival time of 1.3 months. In contrast, patients who underwent aggressive treatment, such as palliative chemotherapy or chemotherapy plus radiotherapy, had significantly longer median survival times. Multivariate analysis revealed that receiving chemotherapy plus radiotherapy was associated with a significant survival benefit compared to no treatment. Furthermore, low PNI (≤40) was independently associated with decreased OS. CONCLUSION: This study highlights the importance of active treatment and nutritional support in improving survival outcomes for very elderly SCLC patients. The findings suggest that low PNI and lack of oncological treatment are associated with worse survival outcomes. Therefore, integrating nutritional assessment, interventions, and appropriate treatment strategies are crucial in managing lung cancer patients. Larger, multicenter studies are needed to validate these findings and explore potential interventions to optimize nutritional status and improve outcomes for elderly patients with SCLC.

Survival results according to Oncotype Dx recurrence score in patients with hormone receptor positive HER-2 negative early-stage breast cancer: first multicenter Oncotype Dx recurrence score survival data of Turkey.

Background: The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions. Patients and methods: Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS. Results: A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18. Conclusion: This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.

Survival of Patients With Metastatic Rectum Cancer Who Underwent Metastasectomy Following Conversion Chemotherapy Sans Pelvic Radiotherapy: A Turkish Oncology Group Study.

BACKGROUND: The management of early rectal cancer is different from that of colon cancer in terms of radiotherapy (RT) requirements or neoadjuvant treatment. It is not clear how the course of rectal cancer differs from that of the colon in a metastatic setting or how it should be approached differently. This study aimed to evaluate outcomes after combining downsizing chemotherapy (CTx) with rescue surgery. METHODS: Eighty-nine patients (57 men and 32 women) diagnosed with metastatic rectal cancer with resectable disease after systemic CTx were included in the study. All patients underwent surgery for the primary mass and metastasis, but none received radiation therapy before or after surgery. Survival curves for overall survival (OS) and progression-free survival (PFS) were generated using the Kaplan-Meier method and compared with the log-rank test for subgroups. RESULTS: The median follow-up time was 28.8 (17.6-39.4) months. During the follow-up, 54 (60.7%) patients died and 78 (87.6%) patients had a PFS event. Cancer relapsed in 72 (80.9%) patients. Median OS was 35.2 (95% CI: 28.5-41.8) months, and median PFS was 17.7 (95% CI: 14.4-21) months. The five-year OS and PFS were 19% and 3.5%, respectively. Male sex (p=0.04) and a better Mandard score (p=0.021) were associated with a longer OS, while obesity was associated with a shorter PFS (p<0.001). CONCLUSION: Our study is the first to evaluate the effects of metastasectomy after conversion therapy in metastatic rectal cancer independent of colon cancer. As a result of the study, it was seen that the survival after metastasectomy in rectal cancer is worse than the colon cancer data known from previous studies.

Cancer-related hypercalcemia and potential treatments.

Cancer-related hypercalcemia is a common finding typically seen in patients with advanced cancer and occurs in about 20 to 30 percent of cases. The most common cause of hypercalcemia in hospitalized patients is hypercalcemia due to malignancy.This clinical problem is seen in patients with both solid tumors and patients with hematologic malignancies. Hypercalcemia is associated with a poor prognosis in oncology patients. This pathologic condition can occur due to many different mechanisms but is usually caused by abnormal calcium use resulting from bone resorption, intestinal absorption, or renal excretion. Hypercalcemia may present with a wide range of symptoms ranging from gastrointestinal system symptoms to neurologic symptoms. Timely diagnosis and initiation of treatment by the physician significantly reduce the risk of complications. Treatment aims to decrease serum calcium by increasing calciuresis, decreasing bone resorption, and decreasing intestinal calcium absorption. The mainstays of treatment are IV hydration, bisphosphonates and calcitonin, denosumab, and in some patients, prednisone, and cinacalcet. Patients with underlying advanced kidney disease and refractory severe hypercalcemia should be evaluated for hemodialysis. Every physician dealing with oncology patients should know the fastest and most effective management of hypercalcemia. We aimed to contribute in this sense.

Efficacy of subsequent treatments in patients with hormone-positive advanced breast cancer who had disease progression under CDK 4/6 inhibitor therapy.

BACKGROUND: There is no standard treatment recommended at category 1 level in international guidelines for subsequent therapy after cyclin-dependent kinase 4/6 inhibitor (CDK4/6) based therapy. We aimed to evaluate which subsequent treatment oncologists prefer in patients with disease progression under CDKi. In addition, we aimed to show the effectiveness of systemic treatments after CDKi and whether there is a survival difference between hormonal treatments (monotherapy vs. mTOR-based). METHODS: A total of 609 patients from 53 centers were included in the study. Progression-free-survivals (PFS) of subsequent treatments (chemotherapy (CT, n:434) or endocrine therapy (ET, n:175)) after CDKi were calculated. Patients were evaluated in three groups as those who received CDKi in first-line (group A, n:202), second-line (group B, n: 153) and ≥ 3rd-line (group C, n: 254). PFS was compared according to the use of ET and CT. In addition, ET was compared as monotherapy versus everolimus-based combination therapy. RESULTS: The median duration of CDKi in the ET arms of Group A, B, and C was 17.0, 11.0, and 8.5 months in respectively; it was 9.0, 7.0, and 5.0 months in the CT arm. Median PFS after CDKi was 9.5 (5.0-14.0) months in the ET arm of group A, and 5.3 (3.9-6.8) months in the CT arm (p = 0.073). It was 6.7 (5.8-7.7) months in the ET arm of group B, and 5.7 (4.6-6.7) months in the CT arm (p = 0.311). It was 5.3 (2.5-8.0) months in the ET arm of group C and 4.0 (3.5-4.6) months in the CT arm (p = 0.434). Patients who received ET after CDKi were compared as those who received everolimus-based combination therapy versus those who received monotherapy ET: the median PFS in group A, B, and C was 11.0 vs. 5.9 (p = 0.047), 6.7 vs. 5.0 (p = 0.164), 6.7 vs. 3.9 (p = 0.763) months. CONCLUSION: Physicians preferred CT rather than ET in patients with early progression under CDKi. It has been shown that subsequent ET after CDKi can be as effective as CT. It was also observed that better PFS could be achieved with the subsequent everolimus-based treatments after first-line CDKi compared to monotherapy ET.

Real-life experience of patients with sarcomatoid renal cell carcinoma: a multicenter retrospective study.

Sarcomatoid renal cell carcinoma (sRCC) is a rare variant of renal cell carcinoma (RCC) and is associated with a poor prognosis. We reviewed the outcomes of patients from oncology centers in Turkey. Our aim is to share our real-life experience and to contribute to the literature. The demographic and clinical features, treatment, and survival outcomes of 148 patients with sRCC were analyzed. The median age at the time of diagnosis was 58 years (range: 19-83 years). Most patients (62.8%) had clear-cell histology. Most patients were in the intermediate Memorial Sloan-Kettering Cancer Center (MSKCC) risk group (67.6%) and were stage 4 at the time of diagnosis (63.5%). The most common sites of metastasis were the lung (60.1%), lymph nodes (47.3%), and bone (35.8%). The patients received a median of two lines (range: 0-6) of treatment. The most common side effects were fatigue, hematological side effects, hypertension, and hypothyroidism. The median follow-up was 20.9 months (range: 1-162 months). The median overall survival (OS) was 30.8 months (95% confidence interval: 24.9-36.7 months). In multivariate analysis, high MSKCC scores, sarcomatoid differentiation rates >50%, having stage 4 disease, and having lung metastasis at the time of diagnosis were independent factors for poor prognosis affecting OS. No difference was observed between patients who received tyrosine kinase inhibitor (TKI) as the first or second-line treatments. Similarly, no difference between TKI and immunotherapy as the second-line treatment. In conclusion, sRCC is a rare variant of RCC with a poor prognosis and response to treatment. Larger-scale prospective studies are needed to define an optimal treatment approach for longer survival in this aggressive variant.

Real life experience of patients with locally advanced gastric and gastroesophageal junction adenocarcinoma treated with neoadjuvant chemotherapy: a Turkish oncology group study.

Neoadjuvant chemotherapy (NACT) in gastroesophageal junction (GEJ) and gastric cancer (GC) was shown to improve survival in recent studies. We aimed to share our real-life experience of patients who received NACT to compare the efficacy and toxicity profile of different chemotherapy regimens in our country. This retrospective multicentre study included locally advanced GC and GEJ cancer patients who received NACT between 2007 and 2021. Relation between CT regimens and pathological evaluation were analysed. A total of 794 patients from 45 oncology centers in Turkey were included. Median age at the time of diagnosis was 60 (range: 18-86). Most frequent NACT regimens used were FLOT (65.4%), DCF (17.4%) and ECF (8.1%), respectively. In the total study group, pathological complete remission (pCR) rate was 7.2%, R0 resection rate 86.4%, and D2 dissection rate was 66.8%. Rate of pCR and near-CR (24%), and R0 resection (84%) were numerically higher in FLOT arm (p > 0.05). Patients who received FLOT had also higher chemotherapy-related toxicity rate compared to patients who received other regimens (p > 0.05). Median follow-up time was 16 months (range: 1-154 months). Estimated median overall survival (OS) was 58.4months (95% CI: 35.2-85.7) and disease-free survival (DFS) was 50.7 months (95% CI: 25.4-75.9). The highest 3-year estimated OS rate was also shown in FLOT arm (68%). We still do not know which NACT regimen is the best choice for daily practice.  Clinicians should tailor treatment regimens according to patients' multifactorial status and comorbidities for to obtain best outcomes. Longer follow-up period needs to validate our results.

Prognostic factors of perioperative FLOT regimen in operable gastric and gastroesophageal junction tumors: real-life data (Turkish Oncology Group).

BACKGROUND: Perioperative FLOT regimen is a standard of care in locally advanced operable gastric and GEJ adenocarcinoma. We aimed to determine the efficacy, prognostic factors of perioperative FLOT chemotherapy in real-life gastric and GEJ tumors. METHODS: The data of patients who were treated with perioperative FLOT chemotherapy were retrospectively analyzed from 34 different oncology centers in Turkey. Baseline clinical and demographic characteristics, pretreatment laboratory values, histological and molecular characteristics were recorded. RESULTS: A total of 441 patients were included in the study. The median of age our study population was 60 years. The majority of patients with radiological staging were cT3-4N(+) (89.9%, n = 338). After median 13.5 months (IQR: 8.5-20.5) follow-up, the median overall survival was NR (95% CI, NR to NR), and median disease free survival was 22.9 (95% CI, 18.6 to 27.3) months. The estimated overall survival at 24 months was 62%. Complete pathological response (pCR) and near pCR was achieved in 23.8% of all patients. Patients with lower NLR or PLR have significantly longer median OS (p = 0.007 and p = 0.033, respectively), and patients with lower NLR have significantly longer median DFS (p = 0.039), but PLR level did not affect DFS (p = 0.062). The OS and DFS of patients with better ECOG performance scores and those who could receive FLOT as adjuvant chemotherapy instead of other regimens were found to be better. NLR was found to be independent prognostic factor for OS in the multivariant analysis. At least one adverse event reported in 57.6% of the patients and grade 3-4 toxicity was seen in 23.6% patients. DISCUSSION: Real-life perioperative FLOT regimen in operable gastric and GEJ tumors showed similar oncologic outcomes compared to clinical trials. Better performance status, receiving adjuvant chemotherapy as same regimen, low grade and low NLR and PLR improved outcomes in real-life. However, in multivariate analysis, only NLR affected OS.

Contribution of "complete response to treatment" to survival in patients with unresectable metastatic colorectal cancer: A retrospective analysis.

BACKGROUND: The aim of the study is to reveal the contribution of complete response (CR) to treatment to overall survival (OS) in patients with unresectable metastatic colorectal cancer. In addition, to evaluate progression-free survival (PFS) in patients who attained CR to treatment and to examine the clinicopathologic features of the patient group with CR. METHODS: This article is a retrospective chart review. Patients diagnosed with metastatic colorectal cancer were divided into two groups. The systemic treatment was compared with the patients who received a full response according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1) and those who did not attain CR (progression partial response and stable response) in terms of both PFS and OS data, and the effect of attaining CR to treatment on prognosis was evaluated. RESULTS: A total of 222 patients were included in the study. 202 of 222 patients could be evaluated in terms of complete response. All data from their files were tabulated and analyzed retrospectively. The mean age of diagnosis of the study group was 60.13 ± 12.52 years. The total number of patients who attained CR to treatment was 31 (15.3%); 171 (84.6%) patients did not attain CR. Patients who had a CR had longer median PFS times than patients who did not have a CR (15.2 vs. 7.4 months, P<0.001). Patients who had CR had longer median survival times than patients who did not have a CR (39.2 vs. 16.9 months, P<0.001). In subgroup patients who underwent primary surgery, the number of patients who attained CR was statistically higher compared with the number of patients who did not attain CR (p<0.001). Complete response was less common in the presence of liver metastasis and bone metastasis (p = 0.041 and p = 0.046, respectively), had a negative prognostic effect. In other words, 89.1% of patients with liver metastasis, 100.0% of patients with bone metastasis, and 88.7% of those who died did not have a CR to the treatment. According to multivariate analysis, CR to treatment, primary surgery, first-line chemotherapy (combination compared with fluoropyrimidine), and no bone metastasis were found to be predictors for OS. CONCLUSION: Providing CR with systemic treatment in patients with unresectable metastatic colorectal cancer (mCRC) contributes to prognosis. The primary resection in our secondary acquisitions from the study, the number of metastatic regions and the combination therapy regimens also contributed to the prognosis.

The effectiveness of cetuximab and panitumumab when combined with FOLFIRI in second-line treatment of KRAS wild type metastatic colorectal cancers. Single centre experience.

Panitumumab and cetuximab are monoclonal antibodies known to be effective in metastatic colorectal cancer (mCRC). Although the survival benefits when combined with chemotherapy have been determined, there are no studies comparing the two agents with chemotherapy in the second-line treatment. In this study, we aimed to compare the efficacy of cetuximab vs panitumumab in patients who previously received chemotherapy. Who progressed after first-line treatment for K-ras wild type mCRC were analyzed. The efficacy of cetuximab vs panitumumab on overall survival (OS) and progression-free survival (PFS) when combined with FOLFIRI regimen was compared retrospectively. Median PFS was 6.9 months in the cetuximab group and 4.7 months in the panitumumab group. Median OS cetuximab and panitumumab groups were 18.4 and 12.2 months, respectively. In the second-line treatment of K-ras wild type mCRC, both PFS and OS were found to be longer in patients receiving cetuximab than in patients receiving panitumumab, but no statistically significant difference was found.