Efficacy of cumulative cisplatin dose on survival in patients with locally advanced cervical cancer treated with definitive chemoradiotherapy: multicenter study by Turkish Oncology Group.

OBJECTIVE: To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy. METHODS: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival. RESULTS: The median cumulative cisplatin dose was 210 mg (range 40-320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1-150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin <10 g/dL before chemoradiotherapy as poor prognostic factors for both progression free survival and overall survival in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose <200 mg was found to be a significant poor prognostic factor in overall survival (hazard ratio 1.79, 95% confidence interval 1.1 to 3.0, p=0.031). CONCLUSION: Our study showed that a cumulative cisplatin dose >200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.

Neoadjuvant Chemotherapy and Pathologic Complete Response in HR+/HER2- Breast Cancer: Impact of Tumor Ki67 and ER Status.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is extensively employed in breast cancer (BC), primarily for aggressive subtypes like triple-negative and human epidermal growth factor receptor 2 (HER2) positive BC, and in estrogen receptor-positive (ER+)/ HER2- BC with high-risk features. In ER+/HER2- breast cancer, pathological complet rates are much lower (<10%), while axillary dissection rates are higher. This study focuses on hormone receptor positive (HR+)/HER2- BC patients undergoing NAC, examining its impact on pathological complete response (pCR) rates, with specific attention to tumor Ki67 and ER status. METHODS: Retrospective data analysis from Kartal Dr. Lütfi Kirdar City Hospital included HR+/HER2- BC patients who received NAC. Clinicopathological factors, NAC response, and surgical outcomes were assessed. Statistical analyses evaluated the association between Ki67, ER status, and pCR. RESULTS: Of 203 patients, 11.8% achieved pCR. Ki67 (p<0.001) and ER percentage (p<0.001) significantly correlated with pCR. Higher Ki67 was associated with increased pCR likelihood (HR: 1.03, 95% CI: 1.01-1.05). A Ki67-pCR probability curve revealed a cutoff of 23.5%. ER%-pCR analysis showed decreasing pCR rates with higher ER percentages. Multivariate analysis confirmed Ki67 (p=0.003, HR: 1.02) and ER percentage (p=0.019, HR: 0.97) as independent predictors of pCR probability. CONCLUSION: Consideration of Ki67 and ER percentage aids in NAC decisions for HR+/HER2- BC, identifying patients with high NAC response rates, facilitating axillary preservation, and potentially avoiding axillary dissection. The pCR rates in patients with Ki67 ≤ 24 are particularly low, especially in patients with a high ER percentage. In these cases, upfront surgery and adjuvant treatment should be considered instead of NAC.

Clinical Effectiveness of Targeted Therapies Following Nivolumab Therapy in Patients with Metastatic Renal Cell Carcinoma: A Real-World Study.

Background: The treatment and escape for metastatic renal cell carcinoma (RCC) has rapidly evolved, particularly with the integration of immune therapies into first-line regimens. However, optimal strategies following progression in first-line immunotherapy remain uncertain. This study aims to evaluate the efficacy and safety of axitinib and cabozantinib as third-line therapies after progression on nivolumab following first-line VEGF-TKI therapy. Methods: Patients with metastatic RCC who progressed on prior nivolumab treatment after receiving first-line VEGF-TKI therapy were included. Data on patient characteristics, treatment regimens, response rates, progression-free survival (PFS), and overall survival (OS) were collected. Statistical analyses were conducted to assess the prognostic factors and treatment outcomes. Results: A total of 46 patients were included who were predominantly male (83%) with clear-cell histology (89%). The median PFS on first-line TKI therapy was 10.2 months. All the patients received nivolumab as a second-line therapy, with a median of 12 cycles. The median second-line PFS was seven months. Third-line therapies included axitinib (24 patients) and cabozantinib (20 patients). The median PFS for axitinib and cabozantinib was six months, with comparable survival outcomes. The IMDC risk group and treatment tolerability were significant predictors of survival in multivariate analysis. Adverse events were manageable, with hypertension, fatigue, and diarrhea being the most common. Conclusion: Axitinib and cabozantinib show promise as third-line therapies post-nivolumab progression in metastatic RCC, though prospective validation is warranted. This study underscores the need for further research to establish treatment standards in this evolving landscape.

Combining Endocrine Therapy with Trastuzumab Emtansine Improves Progression-Free Survival and Overall Survival in HER2-Positive, Hormone Receptor-Positive Metastatic Breast Cancer.

Background and Objectives: Patients with human epidermal growth factor receptor 2 (HER2) -positive, hormone receptor-positive (HR-positive) metastatic breast cancer (MBC) usually undergo trastuzumab emtansine (T-DM1) therapy in subsequent lines. Combining endocrine therapy (ET) with T-DM1 can improve treatment outcomes in this subtype. Therefore, this study aimed to investigate the benefits of using T-DM1 with ET in HER2-positive and HR-positive MBC. This study was the first to investigate the benefits of combining ET with T-DM1. Material and Methods: This study analyzed the medical records of patients with HER2-positive and HR-positive MBC who were treated with T-DM1 from June 2010 to December 2021. The patients were divided into groups based on whether they received concomitant ET with T-DM1. The primary endpoint was to determine the progression-free survival (PFS), while the secondary endpoints were overall survival (OS), objective response rate, and safety of the treatment. Results: Our analysis examined 88 patients, of whom 32 (36.4%) were treated with T-DM1 in combination with ET. The combination therapy showed a significant improvement in median PFS (15.4 vs. 6.4 months; p = 0.00004) and median OS (35.0 vs. 23.1 months; p = 0.026) compared to T-DM1 alone. The ORR was also higher in the combination group (65.6% vs. 29.3%; p = 0.026). Patients treated with pertuzumab priorly had reduced median PFS on T-DM1 compared to those who were not treated with pertuzumab (11.7 vs. 5.4 months, respectively; p < 0.01). T-DM1 demonstrated better median PFS in HER2 3+ patients compared to HER2 2+ patients, with an amplification ratio of >2.0 (10.8 vs 5.8 months, respectively; p = 0.049). The safety profiles were consistent with previous T-DM1 studies. Conclusions: The combination of T-DM1 with ET can significantly improve PFS and OS in patients with HER2-positive and HR-positive MBC. Our study suggests that prior pertuzumab treatment plus trastuzumab treatment might decrease T-DM1 efficacy.

Outcomes of surveillance versus adjuvant treatment for patients with stage-I seminoma: a single-center experience.

INTRODUCTION: Testicular germ cell tumors (seminoma/non-seminoma) are the most common carcinomas in young males, comprising approximately 1% of all carcinomas. In stage-I disease, orchiectomy can cure approximately 85% of patients. Post-surgical options are adjuvant therapy and active surveillance. Our study examined the effects of management options on stage-I seminoma patients followed in our center. METHODS: We evaluated the patients with stage-I testicular seminoma who underwent radical orchiectomy and followed up in the oncology center between 2001 and 2022. The outcomes of management options, survivals were retrospectively analyzed. The prognostic significance of risk factors for relapse on survival was evaluated. RESULTS: Of the 140 patients with stage-I seminoma, 49 (35%) were treated with adjuvant therapy, and 91 (65%) underwent surveillance. The median follow-up duration was 37 months. During the follow-up period, nine patients in the active surveillance group and four in the adjuvant therapy group had a recurrence. There was no statistically significant difference between the two groups (p = 0.67). In the surveillance group, the univariate and multivariate analyzes identified the presence of lymphovascular invasion (p = 0.005, HR: 0.13) as significant prognostic factor for disease-free survival (DFS). In the surveillance cohort, the 5-year DFS rate was 60% for patients with lymphovascular invasion and 93% for those without. There was statistical significance between the two groups (p = 0.003). CONCLUSION: Our study shows that adjuvant therapy does not significantly improve DFS compared to surveillance in patients. In addition, it has been shown that lymphovascular invasion is an important prognostic indicator for DFS in determining the treatment strategy.

Does Proton Pump Inhibitors Decrease the Efficacy of Palbociclib and Ribociclib in Patients with Metastatic Breast Cancer?

Background and Objectives: This investigation aimed to determine the impacts of concurrent proton pump inhibitors (PPIs) on progression-free survival (PFS) in patients with hormone receptor-positive and HER2-negative metastatic breast cancer managed with palbociclib or ribociclib as either the initial or subsequent line of therapy option. Materials and Methods: In this retrospective study, patients were classified as "concurrent PPIs" if PPIs were given for at least two-thirds of the palbociclib or ribociclib therapy period, and "no concurrent PPIs" if no PPIs were given during the period of palbociclib or ribociclib therapy. Each patient was also classified as endocrine-sensitive or endocrine-resistant according to the duration of previous endocrine responses. "Concurrent PPIs" and "no concurrent PPIs" groups were compared with each other in terms of PFS. This comparison was performed for both ribociclib and palbociclib groups. Results: The research included 220 patients in total. The PFS of 57 patients on palbociclib using concomitant PPIs was 14.4 months. Among 63 patients using palbociclib without concomitant PPIs, the PFS was 15.8 months. No statistically significant difference was found with PPI use (p = 0.82). Among 29 patients using ribociclib concurrently with PPIs, the PFS was 22.4 months. Among 71 patients using ribociclib without PPIs, the PFS was 20.2 months. No statistically significant difference was found with PPI use (p = 0.40). Conclusion: The results of our investigation showed that concomitant use of the most commonly used PPIs in the study (lansoprazole, pantoprazole, and esomeprazole) with palbociclib or ribociclib did not have any detrimental effects on PFS. Where appropriate, PPIs can be used concurrently with palbociclib and ribociclib. However, the effect of PPIs on cycling-dependent kinase 4/6 inhibitors deserves further investigation.

Does systemic anti-tumor therapy increase COVID-19 risk in patients with cancer?

PURPOSE: We aimed to determine the COVID-19 infection rate and determine the factors that affect hospitalization and prognosis in patients receiving systemic chemotherapy (CT), immunotherapy (IT) and molecular-targeted therapies at our hospital within three months after the onset of COVID-19 pandemic. MATERIALS AND METHODS: The patients who received systemic treatment at chemotherapy unit with diagnosis of cancer between 11 March 2020 and 11 June 2020 were included. The clinical and demographic characteristics of patients, the systemic treatments that they received (CT, IT, targeted therapies), and the stage of disease were determined. For the parameters that affect the hospitalization of COVID-19 infected patients were also determined. RESULTS: Among 1149 patients with cancer, 84 of them were infected with COVID-19, and the median age of infected patients was 61.0 (IQR: 21-84) and 60.7% of them were male. As a subtype of cancers lung cancer was more frequent in the patients who infected with COVID compared with non-infected ones and the difference was statistically significant when the underlying malignities were compared (32.1% vs 19.0%, p = 0.031). The hospitalization rate and receiving COVID-19 treatment were more frequent in metastatic patients who were receiving palliative therapy, and the difference was statistically significant (p = 0.01, p = 0.03). In our study, infection rate was similar among patients treated with CT, IT and CT plus targeted therapy; however, fewer COVID-19 infections were seen at patients who received only targeted therapy. CONCLUSION: COVID-19 infection is more frequent in cancer patients and tends to be more severe in metastatic cancer patients receiving anticancer treatment, and the continuation of palliative cancer treatments in these patients may cause increased cancer and infection-related morbidity and mortality.

Prognostic factors of ado-trastuzumab emtansine treatment in patients with metastatic HER-2 positive breast cancer.

BACKGROUND: Ado-trastuzumab emtansine is an antibody-drug conjugate that combines the cytotoxic activity of emtansine with human epidermal growth factor receptor 2-targeted antitumor features of trastuzumab. OBJECTIVE: We conducted a study of metastatic breast cancer patients treated with trastuzumab emtansine. By evaluating progression-free survival, overall survival, and response rates, we aimed to find prognostic factors of trastuzumab emtansine treatment. METHODS: Our study is a single-center, retrospective, observational study. We have clinical data from 78 patients treated with trastuzumab emtansine for metastatic breast cancer, from May 2016 through May 2019, at Kartal Dr Lutfi Kirdar Education and Research Hospital, Medical Oncology Department. Our objective is to assess the survival and response rates in trastuzumab emtansine-treated individuals and the factors associated with survival. The factors we analyzed were cancer antigen 15-3 sensitivity, Eastern Cooperative Oncology Group-Performance Status, presence or absence of visceral metastases, presence or absence of cranial metastases, and treatment-associated thrombocytopenia. RESULTS: Among 78 patients, median progression-free survival was 7.8 months, and overall survival was 21.1 months. Twenty of the patients had an objective tumor response. The results showed that trastuzumab emtansine was tolerable with a manageable safety profile and consistent with the results of the previous literature. Mostly seen adverse events were anemia, thrombocytopenia, fatigue, and increased levels of alkaline phosphatase. Patients with Eastern Cooperative Oncology Group-Performance Status = 2 had worse progression-free survival and overall survival compared to ones with Eastern Cooperative Oncology Group-Performance Status < 2; progression-free survival and overall survival are worse in cancer antigen 15-3-sensitive breast cancer patients. According to our findings, treatment-associated thrombocytopenia was a significant prognostic factor for survival. Patients with thrombocytopenia had 12 months progression-free survival, whereas patients without thrombocytopenia had only 4.1 months progression-free survival. In like manner, overall survival was much better in the thrombocytopenia-experienced patients as 29.5 versus 11.8 months. CONCLUSIONS: Trastuzumab emtansine prolongs progression-free survival and overall survival with a manageable safety profile. Thrombocytopenia, Eastern Cooperative Oncology Group-Performance Status, and cancer antigen 15-3 are correlated with progression-free survival and/or overall survival.

Outcomes of surveillance versus adjuvant chemotherapy for patients with stage IA and IB nonseminomatous testicular germ cell tumors.

BACKGROUND: Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. METHODS: A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. RESULTS: Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p < 0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p < 0.001). Univariate analysis showed that the presence of LVI (p = 0.01) and treatment option (p < 0.001) were prognostic factors for RFS and pT stage (p = 0.004) and invasion of rete testis (p = 0.004) and the presence of relapse (p < 0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p < 0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p = 0.031), embryonal carcinoma (EC) >50% (p = 0.013) and tumor diameter (p = 0.016) were found to be independent factors for predicting relapse. CONCLUSIONS: Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.

The impact of immunohistochemical staining with ezrin-carbonic anhydrase IX and neuropilin-2 on prognosis in patients with metastatic renal cell cancer receiving tyrosine kinase inhibitors.

The identification of prognostic factors in patients with renal cell carcinoma (RCC) represents an area of increasing interest. In this retrospective study, we evaluated the prognostic role of carbonic anhydrase-IX, ezrin, and neuropilin in metastatic RCC patients. The expression of several biomarkers were measured by immunohistochemistry (IHC) in 45 patients with advanced stage RCC treated with second-line tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) after failure of interferon-alpha between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. Age, ezrin and neuropilin-2 overexpression were found to be statistically significant factors (P < 0.05) for PFS in the univariate analysis. Ezrin and neuropilin-2 overexpression, hemoglobin and albumin level were statistically significant factors (P < 0.05) for OS in the univariate analysis. Multivariate analysis revealed that low expression of ezrin and neuropilin-2 was an independent prognostic factor for PFS and OS. The median PFS was 4 months for patients overexpressing neuropilin-2 versus 11 months for those with lower expression of neuropilin-2 (p = 0.033). The median OS was longer in patients with low levels of neuropilin-2 expression (26 months) compared to patients overexpressing neuropilin-2 (13 months) (p = 0.023). Increased expression of ezrin was associated with poor prognosis in patients treated with TKIs targeting VEGF (PFS, 3 vs 7 months; p = 0.012). High ezrin expression was associated with shorter OS (p = 0.009). This is the first study in the literature showing that neuropilin-2 and ezrin are related with prognosis in patients with advanced RCC.

KRAS discordance between primary and metastatic tumor in patients with metastatic colorectal carcinoma.

PURPOSE: Adding targeted therapies to chemotherapy in metastatic colorectal cancer (CRC) improves response rates and survival. KRAS is a predictive indicator for anti-epidermal growth factor receptor (EGFR) treatments. The most important reasons for KRAS discordance are intratumoral heterogeneity and incorrect mutation analysis. Evaluating the status of KRAS in primary and metastatic lesions becomes even more crucial to ensure efficient usage of anti-EGFR treatments. METHODS: Patients with metastatic CRC, whose primary disease and liver and/or lung metastases were operated, were retrospectively evaluated, and KRAS assessment was performed on 31 patients who were suitable for DNA analysis. Pyrosequencing with polymerase chain reaction (PCR) was used for KRAS analysis. RESULTS: The median age of 31 patients diagnosed with rectal cancer (N=13) and colon cancer (N=18) was 63 years (range 33-73). Metastasectomy locations included the liver (N=27), lung (N=3), and both lung and liver (N=1). KRAS discordance was detected in 22% (7/31) of the patients. While 3 patients with detected discordance had mutated KRAS in the primary material, wild type KRAS was detected in their liver or lung lesions. On the other hand, while 4 patients had wild type KRAS in the primary material, mutated KRAS was determined in their liver or lung lesions. The McNemar test revealed no significant discordance between primary and metastatic disease (p=1.00). No progression free survival (PFS) difference was detected between patients with determined discordance and patients with undetermined discordance (10.6 vs 14.7 months, p=0.719). CONCLUSION: This is the first study to evaluate KRAS discordance between primary and metastasis in CRC patients, who underwent metastasectomy, together with survival data. In the literature and recent studies with large patient numbers in which modern KRAS tests were used, the KRAS discordance rate varies between 3-12%. In our study, a higher KRAS discordance (22%) was detected, and no survival difference was determined between patients with or without discordance. In recent years, the rising interest in borderline resectable disease may bring forward discussions related to which material the KRAS status should be analyzed.

Impact of adjuvant treatment modalities on survival outcomes in curatively resected pancreatic and periampullary adenocarcinoma.

BACKGROUND: We examined the impact of adjuvant modalities on resected pancreatic and periampullary adenocarcinoma (PAC). METHODS: A total of 563 patients who were curatively resected for PAC were retrospectively analyzed between 2003 and 2013. RESULTS: Of 563 patients, 472 received adjuvant chemotherapy (CT) alone, chemoradiotherapy (CRT) alone, and chemoradiotherapy plus chemotherapy (CRT-CT) were analyzed. Of the 472 patients, 231 were given CRT-CT, 26 were given CRT, and 215 were given CT. The median recurrence-free survival (RFS) and overall survival (OS) were 12 and 19 months, respectively. When CT and CRT-CT groups were compared, there was no significant difference with respect to both RFS and OS, and also there was no difference in RFS and OS among CRT-CT, CT and CRT groups. To further investigate the impact of radiation on subgroups, patients were stratified according to lymph node status and resection margins. In node-positive patients, both RFS and OS were significantly longer in CRT-CT than CT. In contrast, there was no significant difference between groups when patients with node-negative disease or patients with or without positive surgical margins were considered. CONCLUSIONS: Addition of radiation to CT has a survival benefit in patients with node-positive disease following pancreatic resection.

Exploring the Clinical Impact of RANK Pathway Inhibition in Advanced Breast Cancer: Insights From a Retrospective Study on CDK4/6 Inhibitors and Antiresorptive Therapy.

BACKGROUND AND OBJECTIVE: Breast cancer (BC) remains a significant health concern, particularly in advanced stages where the prognosis is poor. The combination of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has improved outcomes for advanced BC (aBC) patients. However, resistance to CDK4/6i remains a challenge, with no validated biomarkers to predict response. The receptor activator of the nuclear factor-kB (RANK) pathway has emerged as a key player in aBC, particularly in luminal BC. RANK overexpression has been associated with aggressive phenotypes and resistance to therapy. In view of these findings, we proceeded to investigate the potential involvement of the RANK pathway in luminal BC resistance to CDK4/6i. The objective was to evaluate the effectiveness of denosumab in increasing overall survival (OS) and progression-free survival (PFS). METHODS: In this retrospective analysis, 158 BC patients with bone metastases were included. Patients with human epidermal growth factor receptor-2 (HER2)-negative and hormone receptor-positive BC who received palbociclib or ribociclib in addition to antiresorptive medication were included. Patients received either denosumab or zoledronic acid (ZA) therapy. The primary endpoint was OS, with PFS as a secondary endpoint. RESULTS: Although the PFS and OS of denosumab were better than ZA in this study, it did not show a significant difference between the two drugs. Meanwhile, mOS was not achievable in patients in the denosumab group, while it was 34.1 months in patients in the ZA group. The hazard ratio (HR) showed a significant improvement for the denosumab group in patients under 60 of age (HR: 0.33, p<0.01), patients with a score of 1 HER2 overexpression (HR: 0.09, p=0.01), and patients with resistant endocrine (HR: 0.42, p=0.02) compared to ZA. CONCLUSION: This study highlights the potential clinical relevance of the RANK pathway in BC treatment, and our findings suggest that denosumab may offer significant benefits in terms of PFS and OS for certain subgroups, particularly those with HER2 scores of 1, patients under 60, and those with endocrine-resistant BC. In conclusion, considering that RANK pathway status may be a predictive biomarker for CDK4/6i treatment and may cause treatment resistance, our results demonstrate the clinical relevance of the combination of CDK4/6i + ET with RANKL inhibition.

A Novel Prognostic Indicator for Immunotherapy Response: Lymphocyte-to-Albumin (LA) Ratio Predicts Survival in Metastatic NSCLC Patients.

OBJECTIVE: Immunotherapies are commonly employed for the treatment of non-small-cell lung cancer (NSCLC). However, predictive biomarkers still need to be improved to predict responses to these agents. The lymphocyte-albumin (LA) laboratory index has not been evaluated before in this patient group. The aim of this study was to analyze the relation between the LA index and the survival rate of metastatic NSCLC patients who had immunotherapy after at least one round of chemotherapy. METHODS: The research included 227 patients diagnosed with metastatic NSCLC, who were administered nivolumab after at least one round of chemotherapy. The LA index was calculated by multiplying lymphocyte count and albumin concentration. The optimal threshold values for the index were established by the examination of the ROC curve for both overall survival (OS) and progression-free survival (PFS). Oncological data were obtained retrospectively from patient files, and survival analyses were performed. RESULTS: The median follow-up was 7.9 months. Progression was observed in 129 (56.9%) patients. A total of 97 (42.7%) patients died during the follow-up. The cutoff values of the LA index to predict OS and PFS were determined as 52.87 and 57.67, respectively. The low-LA group had significantly lowered OS and PFS compared to the high-LA group. LA was found to be an independent prognostic factor for PFS (hazard ratio 4.47; 95% confidence interval, 2.73-7.34; p < 0.001) and OS (hazard ratio 6.24; 95% confidence interval, 3.46-11.25; p < 0.001) in the multivariate regression analysis. CONCLUSIONS: In this study, we observed that the LA index independently predicts OS and PFS in immunotherapy-treated metastatic NSCLC patients. Its ease of application, low cost, and noninvasive nature make it a potential guide for clinicians in predicting treatment responses and survival.

Prognostic scores in pulmonary large cell neuroendocrine carcinoma: A retrospective cohort study.

Introduction: Pulmonary large cell neuroendocrine carcinoma (PLCNEC) is a rare but aggressive subtype of lung cancer with an incidence of approximately 3 %. Identifying effective prognostic indicators is crucial for guiding treatments. This study examined the relationship between inflammatory markers and PLCNEC patient overall survival (OS) and sought to determine their prognostic significance in PLCNEC. Methods: Patients diagnosed with PLCNEC between 2007 and 2022 at the oncology center, were retrospectively included. Patients who underwent surgery were pathologically re-staged post-surgery. Potential prognostic parameters (neutrophil/lymphocyte ratio, platelet/lymphocyte ratio [PLR], panimmune inflammatory value, prognostic nutritional index and modified Glasgow prognostic score [mGPS]) were calculated at that time of diagnosis. Results: Sixty patients were included. The median follow-up was 23 months. Thirty-eight patients initially diagnosed with early or locally advanced. The mGPS was identified as a poor prognostic factor that influenced disease free survival (DFS) fourfold (p = 0.03). All patients' median OS was 45 months. Evaluating factors affecting OS in all patients, statistically significant relationships were observed between OS and the prognostic nutritional index (p = 0.001), neutrophil/lymphocyte ratio (p = 0.03), platelet/lymphocyte ratio (p = 0.002), and pan-immunoinflammatory value (p = 0.005). Upon multivariate analysis, the platelet/lymphocyte ratio was identified as an independent poor prognostic factor for OS, increasing the mortality risk by 5.4 times (p = 0.002). Conclusion: mGPS was significantly linked with prognosis in non-metastatic PLCNEC, with patients with higher mGPS exhibiting poorer long-term DFS. This finding contributes to the evolving understanding of PLCNEC. The multivariable predictive model we employed suggests that PLR is an independent predictor of OS at all stages. A lower PLR was correlated with worse overall survival. Thus, PLR can be a readily accessible and cost-effective prognostic factor in PLCNEC patients.

The role of laboratory indices on treatment response and survival in breast cancer receiving neoadjuvant chemotherapy.

Neoadjuvant chemotherapy (NACT) is the standard treatment for locally advanced, high-risk breast cancer. Pathological complete response (pCR) improves survival. Peripheral blood-derived indices reflecting systemic inflammation and nutritional status have long been used as predictive and prognostic markers in solid malignancies. This retrospective study investigates whether eight commonly used indices in patients receiving NACT affect pCR and survival. This study includes 624 locally advanced breast cancer patients who received NACT. The biomarker indices were calculated from peripheral blood samples taken two weeks before starting chemotherapy. The indices' optimal cut-off values were determined using ROC Curve analysis. During a median follow-up period of 42 months, recurrence was detected in 146 patients, and 75 patients died. pCR was observed in 166 patients (26.6%). In univariate analysis, NLR, PLR, SII, PNI, HALP, and HRR were statistically significantly associated (p = 0.00; p = 0.03; p = 0.03; p = 0.02; p = 0.00; p = 0.02 respectively), but in multivariate analysis, only NLR was significantly predictive for pCR(p = 0.04). In multivariate analysis, the HGB/RDW score significantly predicted DFS(p = 0.04). The PNI score was identified as a marker predicting survival for both OS and PFS (p = 0.01, p = 0.01, respectively). In conclusion, peripheral blood-derived indices have prognostic and predictive values on pCR and survival. However, further studies are needed to validate our findings.

Treatment outcomes and prognostic factors in patients with driver mutant non-small cell lung cancer and de novo brain metastases.

Central nervous system (CNS) metastases can be seen at a rate of 30% in advanced stages for patients with non-small cell lung cancer (NSCLC). Growing evidence indicates the predictive roles of driver gene mutations in the development of brain metastases (BM) in recent years, meaning that oncogene-driven NSCLC have a high incidence of BM at diagnosis. Today, 3rd generation targeted drugs with high intracranial efficacy, which can cross the blood-brain barrier, have made a positive contribution to survival for these patients with an increased propensity to BM. It is important to update the clinical and pathological factors reflected in the survival with real-life data. A multi-center, retrospective database of 306 patients diagnosed with driver mutant NSCLC and initially presented with BM between between November 2008 and September 2022 were analyzed. The median progression-free survival (mPFS) was 12.25 months (95% CI, 10-14.5). While 254 of the patients received tyrosine kinase inhibitor (TKI), 51 patients received chemotherapy as first line treatment. The median intracranial PFS (iPFS) was 18.5 months (95% CI, 14.8-22.2). The median overall survival (OS) was 29 months (95% CI, 25.2-33.0). It was found that having 3 or less BM and absence of extracranial metastases were significantly associated with better mOS and iPFS. The relationship between the size of BM and survival was found to be non-significant. Among patients with advanced NSCLC with de novo BM carrying a driver mutation, long-term progression-free and overall survival can be achieved with the advent of targeted agents with high CNS efficacy with more conservative and localized radiotherapy modalities.

Adjuvant systemic chemotherapy with or without bevacizumab in patients with resected liver metastases from colorectal cancer.

BACKGROUND: We aimed to investigate the impact of adjuvant systemic therapy with modern chemotherapy combinations on survival outcomes in patients with resected liver-confined metastases from colorectal carcinomas, and whether addition of bevacizumab (BEV) provides further benefit. METHODS: A total of 229 consecutive patients who underwent resection for liver-confined colorectal liver metastases were retrospectively analyzed. RESULTS: Of 229 patients, 204 who received chemotherapy with fluoropyrimidine-based (n = 27), irinotecan-based (n = 84) and oxaliplatin-based (n = 93) combinations were analyzed. Among these, 87 patients received BEV while 117 did not (NoBEV). With a median follow-up of 27 months after metastasectomy, the median recurrence-free survival (RFS) and overall survival (OS) were 17 and 53 months, respectively. OS rates at 3 and 5 years were 71% and 40%, respectively. No significant differences were found in the median RFS (p = 0.744) and OS (p = 0.440) among different chemotherapy regimens. The median RFS (p = 0.375) and OS (p = 0.251) were similar in BEV and NoBEV arms. In multivariate analysis, having 4 liver metastases was the only negative independent factor on both RFS and OS, while positive surgical margin was another negative independent factor for RFS. CONCLUSION: Chemotherapy type and addition of BEV have no impact on both RFS and OS in the adjuvant setting following complete resection of colorectal liver metastases.

The role of positron emission tomography with 18F-fluorodeoxyglucose in nodal staging of clinical and radiological N0 head and neck cancers.

The objective of the study was to evaluate the impact of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) imaging on nodal staging for head and neck cancers. This was a retrospectively analyzed single institution study. The study population consisted of 36 patients with head and neck cancers who were evaluated with PET/CT and went on to neck dissection. All of them had clinically and radiographically negative neck (N0) and each patient underwent PET/CT imaging before undergoing selective neck dissection for N0 disease. Tissues were submitted for histopathologic examination and were oriented for the pathologist to permit correlation between the histopathologic findings and the imaging results. The sizes of the lymph nodes and the maximum standardized uptake values (SUVmax) measured from PET/CT images were compared with the histopathologic findings. All primary tumors were visualized with PET/CT. On histopathological examination, 19 patients had positive and 17 patients had negative lymph nodes. Receiver operating characteristic analyses were used to predict the optimal corrected SUVmax cutoffs; the optimal value was 2.95 for respective outcomes of lymph node involvement. This cutoff value yielded 84.2% sensitivity and 76.5% specificity for nodal-level staging. PET/CT proved to be accurate in 27 (75%) patients and inaccurate in 9 (25%) patients. PET/CT was a valuable tool to assess nodal stage of head and neck cancers, and should be considered before surgical treatment.

Retrospective Evaluation of the Efficacy of Gemcitabine-Based Therapies After FOLFIRINOX Failure in Advanced Pancreatic Cancer, Multi-Center Real-Life Data.

OBJECTIVE: Combination therapies such as FOLFIRINOX or gemcitabine-nanoparticle albumin-bound paclitaxel (GnP) are recommended for the first-line treatment of patients with advanced pancreatic cancer. The purpose of this study was to evaluate the efficacy of gemcitabine-based second-line therapies in patients whose disease progressed on FOLFIRINOX. METHOD: Patients diagnosed with advanced pancreatic cancer in 7 tertiary hospitals in Turkey were included. Patients were divided into 3 different groups according to their treatment regimens: GnP, gemcitabine doublet (gemcitabine-cisplatin or gemcitabine-capecitabine), and gemcitabine monotherapy. RESULTS: A total of 144 patients were included in the study. In the second-line treatment, 65% of patients were given GnP, 20% were given gemcitabine doublet, and 15% were given gemcitabine monotherapy. The median exposure of the patients to gemcitabine-based therapy was 3 cycles, whereas the median progression-free survival was calculated as 3.4 months. The median overall survival for patients who received GnP was 4.6 months, 6.4 months for patients who received gemcitabine doublet therapy, and 3.7 months for patients who received gemcitabine monotherapy ( P = 0.248). CONCLUSION: In conclusion, it has been shown that gemcitabine-based second-line treatments contribute to survival in patients with advanced pancreatic cancer. In addition, there was no difference in efficacy between gemcitabine monotherapy or combination treatments.