Efficacy of adjuvant capecitabine in residual triple negative breast cancer: a multicenter observational Turkish Oncology Group (TOG) study.

BACKGROUND: Triple negative breast cancer (TNBC) is characterized by high rates of recurrence, especially in patients with residual disease after neoadjuvant chemotherapy (NAC). Capecitabine is being used as standard adjuvant treatment in residual TNBC. We aimed to investigate the real-life data regarding the efficacy of capecitabine in residual TNBC. DESIGN AND METHODS: In this retrospective multicenter study, TNBC patients with residual disease were evaluated. Patients, who received standard anthracycline and taxane-based NAC and adjuvant capecitabine were eligible. Overall survival (OS), disease free survival (DFS) and toxicity were analyzed. RESULTS: 170 TNBC patients with residual disease were included. Of these, 62.9% were premenopausal. At the time of analysis, the recurrence rate was 30% and death rate was 18%. The 3-year DFS and OS were 66% and 74%, respectively. In patients treated with adjuvant capecitabine, residual node positive disease stood out as an independent predictor of DFS (p = 0.024) and OS (p = 0.032). Undergoing mastectomy and the presence of T2 residual tumor was independent predictors of DFS (p = 0.016) and OS (p = 0.006), respectively. CONCLUSION: The efficacy of capecitabine was found lower compared to previous studies. Selected patients may have further benefit from addition of capecitabine. The toxicity associated with capecitabine was found lower than anticipated.

Prognostic implications of response to neoadjuvant chemotherapy in breast cancer subtypes.

The current study was designed to assess the response to treatment, as well as clinical and survival outcomes, across different breast cancer subtypes in patients who underwent neoadjuvant chemotherapy (NAC). From 2014 to 2019, a total of 139 patients who were histologically confirmed to have breast cancer, underwent NAC, and subsequently received breast and axillary surgery, were retrospectively included in this study. The rates of pathological complete response (pCR) to NAC were significantly higher for HER2-positive and triple-negative subtypes than for luminal A and HER2-negative subtypes (p = 0.013). Multivariate analysis for disease-free survival (DFS) revealed that tumour grade and the presence of pCR were independent prognostic factors. The presence or absence of a pCR with NAC was an independent prognostic indicator in the multivariate analysis for overall survival (OS). Lastly, achieving a pCR was independently predicted by 18F-FDG PET/CT findings, the HER2-positive subtype, and the triple-negative subtype. Despite the inherent methodological limitations, our findings underscore the significance of identifying predictive markers to tailor NAC plans, with the aim of improving survival outcomes.

Beyond traditional therapies: clinical significance of complex molecular profiling in patients with advanced solid tumours-results from a Turkish multi-centre study.

OBJECTIVE: The objective of this multi-centre, real-world study was to examine the potential influence of comprehensive molecular profiling on the development of treatment decisions or adjustments for patients with advanced solid malignancies. We then evaluated the impact of these informed choices on patient treatment outcomes. METHODS: The study encompassed 234 adult patients (mean age: 52.7 ± 14.3 years, 54.7% women) who were diagnosed with solid tumours at 21 different medical centres in Turkey. Remarkably, 67.9% of the patients exhibited metastasis at the time of diagnosis. We utilized an OncoDNA (Gosselies, Belgium) platform (OncoDEEP) integrating next-generation sequencing with additional tests to harvest complex molecular profiling data. The results were analyzed in relation with two specific outcomes: (i) the impact on therapeutic decisions, including formulation or modifications, and (ii) associated treatment response. RESULTS: Out of the 228 patients with final molecular profiling results, 118 (50.4%) had their treatment modified, whilst the remaining 110 (47.0%) did not. The response rates were comparable, with 3.9 versus 3.4% for complete response, 13.6 versus 29.3% for partial response, 66.9 versus 51.7% for progressive disease and 15.5 versus 15.5% for stable disease for treatments informed and not informed by complex molecular profiling, respectively (P = 0.16). CONCLUSION: Our real-world findings highlight the significant impact of complex molecular profiling on the treatment decisions made by oncologists for a substantial portion of patients with advanced solid tumours. Regrettably, no significant advantage was detected in terms of treatment response or disease control rates.

Predictive significance of inflammatory markers and mGPS in metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide.

BACKGROUND: Prostate cancer is a prevalent cancer in men worldwide, and castration-resistant prostate cancer (CRPC) is characterized by disease progression despite androgen deprivation therapy. While clinical and prognostic biomarkers have been identified in CRPC, the significance of serum inflammatory markers remains unclear. MATERIALS AND METHODS: This retrospective study included 79 CRPC patients treated with abiraterone or enzalutamide. Inflammatory markers, including the modified Glasgow prognostic score (mGPS), systemic immune-inflammation index (SII), and neutrophil-to-lymphocyte ratio (NLR), were assessed as predictive tools for treatment response. Patient data were obtained from medical charts, and statistical analyses were performed. RESULTS: The median age of the patients was 67 years, with most having a Gleason score of 8-10. The median values for NLR, PLR, and SII were 2.9, 168.5, and 713.5, respectively. The objective response rate (ORR) to abiraterone or enzalutamide therapy was 55.1%. mGPS showed a significant association with ORR, with the mGPS 0 group having the highest response rate (59.5%). Median progression-free survival (PFS) was 12.8 months, and median overall survival (OS) was 35.4 months. Palliative radiotherapy during therapy and PSA doubling time were independent prognostic factors for PFS. CONCLUSIONS: mGPS and PSA doubling time significantly impacted survival, and mGPS significantly predicted the treatment response in mCRPC, which may lead to further prospective studies.

Survival outcomes of patients with oligometastatic non-small cell lung cancer who were treated with radical therapy: a multicenter analysis.

BACKGROUND: Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. METHODS: This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS: Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5-48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. DISCUSSION: Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2.

Relationship between the change in tumour-infiltrating lymphocyte level and residual tumour after neoadjuvant chemotherapy in patients with locally advanced breast cancer.

To evaluate the tumour-infiltrating lymphocyte (TIL) rates in breast tissue before and after neoadjuvant chemotherapy (NAC) and their impact on survival, eighty-four patients with locally advanced breast cancer (LABC) were assessed. Pre- and post-NAC TIL levels were determined using biopsy and surgical specimens, respectively. The median TIL rate was significantly different before (17.5%) and after (5%) NAC. Pre- and postoperative Ki-67 index, molecular subtype, pre- and post-NAC TIL concentration, and preoperative residual-cancer-burden TIL were significantly associated with pathological complete response (pCR). Specifically, higher pre-NAC TIL levels were associated with higher pCR rates. Postoperative Ki-67 index and pCR, and postoperative Ki-67 index were significant predictors of disease-free (DFS) and overall survival, respectively. The independent prognostic factors for DFS were postoperative Ki-67 score (hazard ratio [HR]: 6.16; p = 0.012), post-NAC TIL score (HR: 0.42; P = 0.041), and pCR (HR: 0.10; P = 0.038). Our study confirms that higher pre-NAC and lower postoperative TIL levels may be surrogate factors for longer DFS, and postoperative TIL rate may predict post-NAC pCR in patients with LABC.

Is there any prognostic significance in pleural involvement and/or effusion in patients with ALK-positive NSCLC?

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.

The Prognostic Role of Mismatch Repair Status and CDX-2 Expression with Inflammatory Markers and Pathological Risk Factors in Stage II and III Colon Cancer: Multicenter Real-Life Data.

OBJECTIVE: Colorectal cancer is common worldwide, and adjuvant treatment's benefit is still controversial. We designed this study to determine the role of MSI and CDX-2 status determined by immunohistochemistry (IHC) combined with the inflammatory markers and pathological parameters in predicting disease recurrence in stage II and III colon cancer. METHODS: A total of 226 stage II/III colon cancer patients with a median age of 59 years who underwent initial surgery were included in this retrospective study. The pathologic assessment of MSI and CDX-2 was performed twice by immunohistochemistry (IHC) and two different pathologists. No staining/weak staining below 10% of the tumor was accepted as CDX-2 negative, and any MSI clones with weak staining below 10% were accepted as MSI-H. The laboratory parameters were noted at the initial diagnosis. RESULTS: One hundred twenty-one and 105 patients were diagnosed with stage III and II colon cancer. 58.0% of patients were male, 46 (20.4%) of tumor tissue were MSS, and 17 (7.5%) were CDX-2 negative. One hundred twenty-nine tumors were localized in the right colon. Disease recurrence was significantly correlated with tumor localization, CDX-2 status, stage at diagnosis, and preoperatively median CRP and CEA levels. DFS rates for MSS patients with CDX-2 negative and positive were 36.7% and 98.1%, respectively [p < 0.001]. There was no significant correlation between MSI status and CDX-2 status. MSI status, the presence of adjuvant treatment, and systemic inflammatory markers were not significant prognostic factors for DFS. CDX-2 status [HR:0.08, CI 95% 0.03-0.17, p < 0.001 HR: 1.7, CI 95% 1.1-3.0, p = 0.03], disease stage [HR:2.6, CI 95% 1.43-4.74], and preoperatively CEA levels [HR:4.1 CI 95% 2.18-785, p < 0.001 were independent significant prognostic factors for DFS. CONCLUSION: CDX-2 loss was an independent prognostic factor for DFS and disease recurrence in early-stage colon cancer. MSS patients with CDX-2 loss had significantly worse survival outcomes, and this might be the reason for deciding on adjuvant chemotherapy.

Prognostic factors for regorafenib treatment in patients with refractory metastatic colorectal cancer: A real-life retrospective multi-center study.

Regorafenib, an oral multikinase inhibitor, has improved survival in metastatic colorectal cancer (mCRC) patients who have progressed on standard therapies. Our study aimed to evaluate prognostic factors influencing regorafenib treatment and assess the optimal dosing regimen in a real-life setting. We retrospectively analysed 263 patients with mCRC from multiple medical oncology clinics in Turkey. Treatment responses and prognostic factors for survival were evaluated using univariate and multivariate analysis. Of the patients, 120 were male, and 143 were female; 28.9% of tumors were located in the rectum. RAS mutations were present in 3.0% of tumors, while BRAF, K-RAS, and N-RAS mutations were found in 3.0%, 29.7%, and 25.9% of tumor tissues, respectively. Dose escalation was preferred in 105 (39.9%) patients. The median treatment duration was 3.0 months, with an objective response rate (ORR) of 4.9%. Grade ≥ 3 treatment-related toxicity occurred in 133 patients, leading to discontinuation, interruption, and modification rates of 50.6%, 43.7%, and 79.0%, respectively. Median progression-free survival (PFS) and overall survival (OS) were 3.0 and 8.1 months, respectively. RAS/RAF mutation (hazard ratio [HR] 1.5, 95% confidence interval [CI] 1.1-2.3; P = 0.01), pretreatment carcinoembryonic antigen (CEA) levels (HR 1.6, 95% CI 1.1-2.3; P = 0.008), and toxicity-related treatment interruption or dose adjustment (HR 1.6, 95% CI 1.1-2.4; P = 0.01) were identified as independent prognostic factors for PFS. Dose escalation had no significant effect on PFS but was associated with improved OS (P < 0.001). Independent prognostic factors for OS were the initial TNM stage (HR 1.3, 95% CI 1.0-1.9; P = 0.04) and dose interruption/adjustment (HR 0.4, 95% CI 0.2-0.9; P = 0.03). Our findings demonstrate the efficacy and safety of regorafenib. Treatment line influences the response, with dose escalation being more favorable than adjustment or interruption, thus impacting survival.

Clinicopathological and Survival Characteristics of Mismatch Repair Status and PD-1 Expression in Serous Ovarian Cancer.

OBJECTIVE: To evaluate the clinicopathological characteristics of mismatch repair (MMR) deficiency and its clinical outcomes by performing immunohistochemistry (IHC) for MMR genes in the serous ovarian cancer (SOC) tumour sections. STUDY DESIGN: A retrospective case-control study. Place and Duration of the Study: Gynecology Department of Kanuni Sultan Süleyman Training and Research Hospital, and Department of Medical Oncology of Medipol University, between March 2001 and January 2020. METHODOLOGY: IHC was carried out for MLH1, MSH2, MSH6, and PMS2 on full-section slides from 127 SOCs to evaluate the MMR status. MMR-negative and MMR-low groups together were defined as MMR deficient and called microsatellite instability-high (MSI-H). The MSI status and expression of programmed cell death-1 (PD-1) were compared in SOCs with different MMR statuses. RESULTS: A significantly higher frequency of MMR-deficient SOCs was diagnosed at early stages compared with the patients in the MSS group (38.6% and 20.6%, respectively, p=0.022). The frequency of cases with PD-1 expression was significantly higher in the MSI-H group (76.2%) than in the MSS counterparts (58.8%, p=0.028). Patients in the MSI-H group had significantly longer DFS (25.6 months) and OS (not reached) than those in the MSS group (16 months and 48.9 months, p=0.039 and p=0.026, respectively). CONCLUSION: MSI-H SOCs were diagnosed at an earlier stage as compared to MMR proficient cases. The presence of PD-1 expression was significantly higher in cases presenting MMR deficiency compared with MMR-proficient cases. MSI status was significantly associated with DFS and OS. KEY WORDS: Serous ovarian cancer, Microsatellite instability, Mismatch repair deficiency.

Major and minor salivary gland cancers: A multicenter retrospective study.

BACKGROUND: Most of the studies on salivary gland cancers are limited for various reasons such as being single-center, small number of patients, including only major or minor SGCs, or only including epidemiological data. METHODS: A total of 37 medical oncology clinics from different regions of Turkey participated in this retrospective-multicenter study. The analyzed data included clinical and demographical features, primary treatment, metastasis localizations, and treatments and includes certain pathologic features. RESULTS: The study included data from a total of 443 SGCs. 56.7% was in major salivary glands and 43.3% was in minor salivary glands. Distant metastasis in the major SGCs was statistically significantly more common than in the minor SGCs, locoregional recurrence was statistically significantly more common in the minor SGCs than in the major SGCs (p = 0.003). CONCLUSIONS: Epidemiological information, metastasis and recurrence patterns, treatment modalities, and survival analysis of the patients over 20 years of follow-up are presented.

Impact of adding pertuzumab to trastuzumab plus chemotherapy in neoadjuvant treatment of HER2 positive breast cancer patients: a multicenter real-life HER2PATH study.

AIM: To investigate the pathological complete response (pCR) achieved after neoadjuvant therapy with versus without adding pertuzumab (P) to trastuzumab (H) plus neoadjuvant chemotherapy (NCT) in HER2+ breast cancer (BC) patients in a real-life setting. METHODS: A total of 1528 female HER2+ BC patients who received NCT plus H with or without P were included in this retrospective real-life study. Primary endpoint was pCR rate (ypT0/Tis ypN0). Clinicopathological characteristics, event-free survival (EFS) time, and relapse rates were evaluated with respect to HER2 blockade (NCT-H vs. NCT-HP) and pCR. RESULTS: Overall, 62.2% of patients received NCT-H and 37.8% received NCT-HP. NCT-HP was associated with a significantly higher pCR rate (66.4 vs. 56.8%, p < 0.001) and lower relapse (4.5 vs. 12.2%, p < 0.001) in comparison to NCT-H. Patients with pCR had a significantly lower relapse (5.6 vs. 14.9%, p < 0.001) and longer EFS time (mean(SE) 111.2(1.9) vs. 93.9(2.7) months, p < 0.001) compared to patients with non-pCR. Patients in the NCT-HP group were more likely to receive docetaxel (75.0 vs. 40.6%, p < 0.001), while those with pCR were more likely to receive paclitaxel (50.2 vs. 40.7%, p < 0.001) and NCT-HP (41.5 vs. 32.1%, p < 0.001). Hormone receptor status and breast conservation rates were similar in NCT-HP vs. NCT-H groups and in patients with vs. without pCR. Invasive ductal carcinoma (OR, 2.669, 95% CI 1.596 to 4.464, p < 0.001), lower histological grade of the tumor (OR, 4.052, 95% CI 2.446 to 6.713, p < 0.001 for grade 2 and OR, 3.496, 95% CI 2.020 to 6.053, p < 0.001 for grade 3), lower T stage (OR, 1.959, 95% CI 1.411 to 2.720, p < 0.001) and paclitaxel (vs. docetaxel, OR, 1.571, 95% CI 1.127 to 2.190, p = 0.008) significantly predicted the pCR. CONCLUSIONS: This real-life study indicates that adding P to NCT-H enables higher pCR than NCT-H in HER2+ BC, while pCR was associated with lower relapse and better EFS time.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as prognostic markers in patients with extensive-stage small cell lung cancer treated with atezolizumab in combination with chemotherapy.

Atezolizumab is now the standard treatment for extensive-stage small cell lung cancer (ES-SCLC). Herein, we investigated the prognostic role of inflammatory markers in patients treated with atezolizumab plus chemotherapy and evaluated the efficacy and safety of adding atezolizumab to chemotherapy for patients with ES-SCLC and prognostic and predictive factors as a real-life experience. This retrospective study included 55 patients who received front-line atezolizumab with etoposide plus platin regimen for ES-SCLC. We analyzed the survival outcomes and factors that may predict response and survival. The objective response rate (ORR) was 81.8%. At a median follow-up of 23.5 months, the median progression-free survival (PFS) time was 10.8 months, and the median overall survival (OS) time was 15.2 months. In univariate analysis for PFS, limited-stage disease at the time of diagnosis, the presence of prophylactic cranial irradiation (PCI), the presence of liver metastasis, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were found to be prognostic factors (P = .041, P = .034, P = .031, P = .004, and P = <.001, respectively). In other words, while the median PFS time was 14.1 months in patients with PLR ≤ 135.7, it was 7.5 months in patients with > 135.7. Similarly, median PFS was 14.9 months in patients with NLR ≤ 3.43, while it was 9.6 months in patients with > 3.43. Univariate analysis for OS revealed that limited stage at the time of diagnosis, NLR and PLR were significant prognostic indicators (P = .01, P = .006, and P = .007, respectively). Median OS time for patients with both NLR ≤ 3.43 and PLR ≤ 135.7 was significantly better than that of patients with NLR > 3.43 and PLR > 135.7 (16.9 vs 11.3 and 16.9 vs 11.5 months, respectively). Logistic regression analysis demonstrated that PLR was an independent significant predictive factor for the response to atezolizumab plus chemotherapy (OR: 0.07, P = .028). The patients with PLR ≤ 135.7 were significantly good responders to atezolizumab plus chemotherapy treatment. Real-life data demonstrated a significant correlation between survival and NLR and, PLR in ES-SCLC patients treated with atezolizumab. In addition, PLR was a significant predictive indicator of response to atezolizumab plus chemotherapy.

The SOCS-1 -1478CA/del functional polymorphism (rs33989964) is associated with gastric cancer but is unrelated to overall survival.

BACKGROUND: In vitro studies have shown that the functional - 1478CA > del polymorphism (rs33989964) of the suppressor of cytokine signaling (SOCS)-1 gene is associated with an altered trascriptional activity. Here, we sought to examine the potential association of this polymorphism with the risk of gastric cancer (GC) and to analyze its prognostic impact on overall survival (OS). MATERIALS AND METHODS: The study cohort consisted of 74 Turkish patients with GC and 52 healthy controls. Genotyping of the SOCS-1 -1478CA > del polymorphism was carried out using restriction fragment length polymorphism analysis. RESULTS: After allowance of age and sex, multivariable logistic regression analysis revealed that the carriage of the del allele of the SOCS-1 -1478CA > del polymorphism was independently associated with an increased risk of GC (odds ratio = 6.78, 95% confidence interval = 3.24-10.99, P < 0.001). Kaplan-Meier analysis revealed no significant differences in OS for patients harboring at least one del allele of rs33989964 compared with CA/CA homozygotes (log-rank test, P = 0.17). CONCLUSION: While the SOCS-1 -1478CA > del polymorphism is significantly associated with the risk of GC in the Turkish population, it does not affect OS.

Five-Year Outcome and Safety in Patients Treated With Immune Checkpoint Blockade Therapies for Urothelial Carcinoma: Experience From Real-World Clinical Practice.

BACKGROUND: In this study, we report real-world results from the 5-year follow-up data of urothelial carcinoma patients treated with immune checkpoint blockade therapies (ICTs). PATIENTS AND METHODS: Metastatic urothelial carcinoma patients treated with at least one course of ICT were included in the study. The primary endpoint was overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), duration of treatment with ICT, and safety. Median follow-up, PFS, and OS were estimated by using the Kaplan-Meier method. RESULTS: Data of 201 eligible patients were analyzed. The median age of the patients was 66 (37-86) years, and 156 (84.3%) were male. The majority of patients (94.6%) had Eastern Cooperative Oncology Group (ECOG) PS scores of 0 to 1 and primary tumor in the bladder was predominant (87.5%). The median follow-up time was 54 (1.15-65) months. The rate of complete response (CR) to ICT, partial response (PR) rate, and ORR were 10.4% (n = 21), 22.4% (n = 45), and 32.4% (n = 66), respectively. The median duration of response (DOR) was 34.8 months (95% confidence interval [CI], 29.2-42.1). Of the 66 patients who responded to treatment, 28 (42%) had an ongoing response at the time of the analysis. Median PFS and OS were 3.8 (2.6-5.8) months and 9.4 (7.4-11.4) months, respectively. The 5-year PFS and OS rates were 9.8% and 12.8%, respectively. Fifty-eight percent of patients experienced a treatment-related adverse event of any grade, and 33 (16.4%) patients had a grade 3 to 4 adverse event. CONCLUSION: This 5-year analysis of real-world data confirms the durable response and long-term survival with ICT in metastatic urothelial carcinoma patients.

Pretreatment platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio as a predictor of pathological complete response to neoadjuvant chemotherapy in patients with breast cancer: single center experience from Turkey.

The aim of this study was to investigate the predictive value of PLR and NLR as an indicator of pathological complete response (pCR) in patients with breast cancer after NACT. One hundred thirty-nine patients with early or LABC and candidates to NACT were retrospectively analyzed. The prognostic significance of PLR and NLR was analyzed. In addition, predictive indicators of pCR to NACT were also evaluated. pCR was obtained in 48.9% of patients. Significant difference was detected between pCR and PLR, tumor grade, clinical lymph node status and molecular subgroup. The higher rate of pCR was significantly achieved for patients with PLR low ( < 181.7) compared with those with PLR high (>181.7) (68.6% vs. 33.4%; P < 0.001). PLR, tumor grade and pCR to NACT for disease-free survival (DFS), and PLR, NLR, tumor grade and pCR to NACT for overall survival were detected to be prognostic factors by univariate analysis. On the other hand, a logistic regression analysis indicated that PLR and NLR were found to be an independent factors for predicting pCR to NACT ( P < 0.001; OR, 0.07; 95% CI, 0.02-0.25 and P = 0.016; OR, 4.66; 95% CI, 1.33-16.2, respectively), as were molecular subtypes ( P = 0.001; OR, 0.23; 95% CI, 0.09-0.56). Our results showed that PLR low and NLR low before NACT are readily feasible and simple and also inexpensive biomarkers predicting pCR to NACT for patients with LABC.

High expression of CD8 in the tumor microenvironment is associated with PD-1 expression and patient survival in high-grade serous ovarian cancer.

Objective: The current study assesses programmed death-1 (PD-1) receptor expression and CD3, CD4, and CD8 tumor-infiltrating lymphocytes (TILs) in high-grade serous ovarian cancer (HGSOC) and associates our results with neoadjuvant chemotherapy history and disease prognosis. Materials and Methods: We included cases diagnosed with primary HGSOC with biopsy or surgical resection materials in this study. The immunoreactivity of CD3, CD4, CD8, and PD1 was assessed immunohistochemically in tumor tissue. We analyzed TILs in two predetermined groups of high and low TIL. The relationships between clinical characteristics, PD-1, and TIL were assessed. by the χ(2) test or Fisher's Exact test. We used Kaplan-Meier survival analysis and Cox proportional hazards regression model to the connection between survival and the amounts of TIL, and PD1. Results: Univariate analysis demonstrated that optimal debulking (p<0.001), early International Federation of Gynecology and Obstetrics stage (p=0.046), and higher scores of stromal CD8+ TIL expression (p=0.028) in tumor cells were all substantially correlated with longer disease-free survival (DFS), whereas the remaining variables analyzed, including PD-1 positivity, stromal CD3+, and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs, were not correlated with DFS. Also, univariate analysis revealed that optimal debulking (p=0.010), and higher scores of stromal CD8+ TIL expression (p=0.021) in tumor cells were all substantially correlated with longer overall survival (OS). Conclusion: Higher scores of stromal CD8+ TILs are substantially correlated with DFS and OS in univariate analyses, whereas scores of stromal CD3+ and CD4+ TILs, and intraepithelial CD3+, CD4+, and CD8+ TILs are not correlated with DFS and OS in both univariate and multivariate analyses. Also, we found a significant association between PD-1 positivity and the scores of stromal CD3+ TILs and intraepithelial CD8+ TILs. However, no remarkable relationship was revealed between PD-1 positivity and the survival of HGSOC cases.

Real-life analysis of treatment approaches and the role of inflammatory markers on survival in patients with advanced biliary tract cancer.

OBJECTIVES: Advanced-stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients. METHODS: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed. RESULTS: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice (p < .001 HR:0.70 CI95% 0.55-0.9), performance status (p < .001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = .02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < .001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < .001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = .002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < .001 HR:0.55 CI 95% 0.38-0.79; p = .007 HR:0.51 CI95% 0.31-0.83, respectively). CONCLUSION: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions.

Atezolizumab combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer: a real-life data of the Turkish Oncology Group.

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.

The Role of 18F-FDG PET/CT in Predicting the Neoadjuvant Treatment Response in Patients with Locally Advanced Breast Cancer.

Purpose: Patients with locally advanced breast cancer (LABC) should be treated with neoadjuvant chemotherapy (NAC). Pathological complete response (pCR) is related to better disease-free survival (DFS). The best strategy for assessing the efficacy of NAC has not been established yet, but several studies have shown that 18F-FDG PET/CT is a potential imaging tool for assessing pCR. The aim of this study is to investigate the merits of 18F-FDG PET/CT imaging in predicting pCR in both axillary and breast tissue and to establish a threshold maximum standard uptake value (SUVmax) for predicting the response after completion of NAC. Methods: A total of 186 LABC patients, treated with an NAC regimen according to tumor subtype, were retrospectively analyzed in this study. All patients underwent 18F-FDG PET/CT imaging before and after completion of NAC. PET parameters were measured in the most FDG avid breast tissue and axillary lymph nodes. We analyzed the correlation between the tumor SUVmax of the PET/CT response and the pCR after surgery. DFS was also evaluated with respect to pCR. Results: Higher pCR rates were significantly associated with a higher tumor grade, an initial Ki-67 ≥20% (p = 0.03 and p = 0.003, respectively), a triple-negative subtype (32.9%), and a human epidermal growth factor receptor 2 (HER-2)-positive subtype (24.7%) (p < 0.001). There was a significant correlation between the pCR and a complete response in 18F-FDG PET/CT (p < 0.001). The overall sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 18F-FDG PET/CT to determine the pCR after NAC were 100%, 72.2%, 85%, 75.2%, and 100%, respectively. We demonstrated a 1.1 cutoff SUVmax for breast tumors after NAC (OR: 3.94, 95% CI: 1.14-5.05, p = 0.004), the 18F-FDG PET/CT response to NAC (OR: 0.50, 95% CI: 0.25-0.99, p = 0.003), and the molecular subtype of breast tumors (OR: 0.58, 95% CI: 0.38-0.88, p = 0.011). Conclusion: Our results confirm that 18F-FDG PET/CT is a useful method for predicting the NAC response in LABC.