The effect of concomitant proton pump inhibitor use on survival outcomes of Nivolumab-treated renal cell carcinoma patients: a multicenter study.

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

Comparison of prognostic value of different metabolic response criteria determined by PET/CT in patients with metastatic breast cancer under CDK 4/6 inhibitor treatment.

PURPOSE: This study evaluates the prognostic role of different [18F]FDG PET/CT metabolic response criteria in metastatic breast cancer (MBC) patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK 4/6). MATERIALS AND METHODS: We retrospectively evaluated the data of MBC patients treated with CDK 4/6 inhibitors who underwent an [18F]FDG PET/CT scan before starting and during treatment. [18F]FDG PET/CT response was assessed with the European Organization for Research and Treatment of Cancer (EORTC), PET Response Criteria in Solid Tumors (PERCIST), and whole-body total lesion glycolysis (WBTLG) criteria. Fleiss kappa was computed to assess the agreement between metabolic response criteria. The endpoint of the study was progression-free survival (PFS). PFS data were analyzed by the Kaplan-Meier method and compared using the log-rank test. RESULTS: The study included sixteen MBC patients who received CDK 4/6 inhibitors therapy. According to PERCIST, partial metabolic response (PMR) was found in seven patients, stable metabolic disease (SMD) in seven patients, and progressive metabolic disease (PMD) in two patients. According to EORTC, PMR was detected in eight patients, SMD in seven patients, and PMD in one patient. According to WBTLG, PMR was found in 10 patients, SMD in four patients, and PMD in two patients. There was a fair agreement between the three criteria. While progression was detected in seven of the patients during follow-up, no progression was detected in nine of them. Kaplan-Meier analysis revealed that the responders according to WBTLG showed significantly longer PFS than non-responders. CONCLUSION: Treatment response according to WBTLG criteria during treatment appears to be associated with prolonged PFS in patients treated with CDK 4/6 inhibitors for MBC.

Efficacy and safety of folfiri plus aflibercept in second-line treatment of metastatic colorectal cancer: Real-life data from Turkish oncology group.

Aims: The addition of aflibercept to the fluorouracil and irinotecan (FOLFIRI) regimen significantly improved clinical outcomes in patients with metastatic colorectal cancer (CRC) previously treated with oxaliplatin. We aimed to investigate the efficacy and safety of second-line FOLFIRI and aflibercept combination in patients with metastatic CRC in real-life experience. Materials and Methods: Four hundred and thirty-three patients who treated with FOLFIRI and aflibercept in the second-line were included in the study. The clinical and pathological features of the patients were recorded retrospectively. Survival (overall and progression-free survival [PFS]), response rates, and safety data were analyzed. Results: The median age was 61. Majority of patients (87.5%) received first-line bevacizumab and 10.1% of patients received anti-epidermal growth factor receptor agents. About 80% of patients had KRAS, 18.6% of patients had NRAS, and 6.4% of patients had BRAF mutations. The median OS was 11.6 months (95% confidence interval [CI], 10.6-12.6) and the median PFS was 6 months (95% CI, 5.5-6.5). About 4.6% of patients had complete response and 30.6% of patients had partial response as best tumor response. Grade 1-2 toxicities were seen in 33.4% of patients, while grade 3-4 toxicities were recorded in 27% of patients. Eight patients (2%) died due to treatment toxicity. Conclusions: Overall and PFS were similar in routine clinical practice compared to phase III pivotal VELOUR trial. However, response rates were found to be higher. It was observed that there were fewer adverse events compared to the VELOUR trial.

Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: Outcomes of survival, toxicity, sphincter preserving and prognostic factors.

BACKGROUND: This study aimed to compare preoperative chemoradiotherapy (CRT) with postoperative CRT regarding survival, local control, disease control, sphincter preservation, toxicity and also prognostic factors for the treatment of locally advanced rectal cancer. METHODS: Records of 140 patients with locally advanced rectal cancer who received preoperative or postoperative CRT were analyzed retrospectively. We compared the treatment groups (preoperative vs postoperative) according to baseline characteristics (demographic and rectal cancer disease characteristics), and also carried out the survival analyses. RESULTS: From January 2010 to December 2019, 140 patients were included in the analysis, 65 received preoperative treatment and 75 postoperative treatment. There was no difference in survival, recurrence or distant metastasis rate in both treatment groups. The ratios of the failure to complete adjuvant chemotherapy (32% vs 4.6%) and acute grade 3-4 toxicity (32% vs 6.2%) were higher in the postoperative group (p < 0.001). In lower located tumors (≤5 cm from anal verge) the ratio of the sphincter preserving in the preoperative group was 60.7% (n = 17/28), and was 16.6% (n = 3/18) in the postoperative group (Yates χ2 = 5.829, p = 0.005). CONCLUSION: This study showed no difference in recurrence and survival rate. Preoperative CRT is the preferred treatment for patients with locally advanced rectal cancer, given that it is associated with a superior overall treatment compliance rate, reduced toxicity, and an increased rate of sphincter preservation in low-lying tumors, but not for overall survival.

Bilateral synchronous adrenal metastasis of invasive ductal carcinoma treated with multimodality therapy including adrenalectomy and oophorectomy.

A 38-year-old woman presented with a mass in the left breast. Biopsy of the lesion revealed invasive ductal carcinoma. Bilateral adrenal metastasis was detected in whole body positron emission tomography scanning. Needle biopsy of the left adrenal lesion proved infiltration of malignant cells from breast carcinoma. After eight cycles of neoadjuvant (preoperative) chemotherapy, mastectomy, bilateral adrenalectomy, and bilateral oopherectomy were performed. No further hormonal treatment was recommended due to the resection of both adrenal glands and ovaries. The patient is still followed without any sign of progression. To our knowledge, this is the first case representing multimodality approach to breast cancer with bilateral synchronous adrenal metastasis. Patients with oligometastatic disease may benefit from aggressive treatment including local therapies.

Safety, Feasibility, and Efficacy of Capecitabine Maintenance in Patients With Advanced Gastric Cancer: A Retrospective Study.

Gastric cancer is still one of the cancers with highest mortality. Most patients present with advanced-stage disease. Palliative chemotherapy is usually the only treatment option for patients with advanced gastric cancer (AGC). Maintenance chemotherapy is an evolving concept in medical oncology. Maintenance chemotherapy can be administered with the same drug(s) in the initial regimen or with an alternative agent. In this article, we report our experience with capecitabine as a maintenance agent for patients with AGC. No treatment-related death was observed due to use of capecitabine. Median progression-free survival was 10.4 months, and median overall survival was 19.7 months. Activity and toxicity profile of capecitabine seems favorable as a maintenance agent in AGC. We believe that capecitabine deserves further trials as a maintenance agent for patients with AGC.

Metastasis of Gastric Signet-Ring Cell Carcinoma to the Urinary Bladder: A Case Report and Review of the Literature.

Although signet-ring cell (SRC) adenocarcinoma is commonly seen in the stomach, it is a very rarely seen histologic entity in the bladder. It is difficult to distinguish primary SRC adenocarcinoma of the bladder from bladder metastasis of SRC carcinoma of the stomach only based on histological findings. In such cases, clinical findings and immunohistochemical studies may be helpful. We present here a 48-year-old male patient presenting with hematuria and abdominal pain. Computerised tomography of the patient revealed a gastric mass, peritoneal involvement, and thickening of the bladder wall, and histopathological analysis revealed SRC adenocarcinoma in both of the endoscopic biopsies taken from the stomach and bladder. Immunohistochemical analyses confirmed the diagnosis of SRC adenocarcinoma of the bladder secondary to gastric cancer.

Revisiting post-gastrectomy anemia with a brief survey among a group of Turkish medical oncologists.

PURPOSE: Total or subtotal gastrectomy are performed as curative or palliative treatment in patients with gastric cancer. Anemia is a frequent complication of gastrectomy. Patients undergoing total or subtotal gastrectomy should be carefully monitored for the development of anemia and be given appropriate treatment when indicated. This survey-based study aimed to determine the level of knowledge about post-gastrectomy anemia in Turkish medical oncologists. METHODS: The study included 110 Turkish medical oncologists that agreed voluntarily to participate in the survey and answer an 8-item questionnaire. The survey was distributed as a questionnaire during the 5th Turkish Medical Oncology Congress in March 2014. RESULTS: All participants completed the questionnaire. Most of the participants would not recommend oral iron or cobalamin replacement after gastrectomy. CONCLUSION: The results of the survey indicate that Turkish medical oncologists have some knowledge about post-gastrectomy anemia, but need to learn more about appropriate follow-up and replacement therapies for post-gastrectomy anemia.

Comparison of metabolic and anatomic response to chemotherapy based on PERCIST and RECIST in patients with advanced stage non-small cell lung cancer.

BACKGROUND: The aim of this study was to explore the prognostic role of metabolic response to chemotherapy, determined by FDG-PET, in patients with metastatic non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: Thirty patients with metastatic NSCLC were analyzed for prognostic factors related to overall survival (OS) and progression free survival (PFS). Disease evaluation was conducted with FDG-PET/CT and contrast-enhanced CT prior to and at the end of first-line chemotherapy. Response evaluation of 19 of 30 patients was also performed after 2-3 cycles of chemotherapy. Morphological and metabolic responses were assessed according to RECIST and PERCIST, respectively. RESULTS: The median OS and PFS were 11 months and 6.2 months, respectively. At the end of first-line chemotherapy, 10 patients achieved metabolic and anatomic responses. Of the 19 patients who had an interim response analysis after 2-3 cycles of chemotherapy, 3 achieved an anatomic response, while 9 achieved a metabolic response. In univariate analyses, favorable prognostic factors for OS were number of cycles of first-line chemotherapy, and achieving a response to chemotherapy at completion of therapy according to the PERCIST and RECIST. The OS of patients with a metabolic response after 2-3 cycles of chemotherapy was also significantly extended. Anatomic response at interim analysis did not predict OS, probably due to few patients with anatomic response. In multivariate analyses, metabolic response after completion of therapy was an independent prognostic factor for OS. CONCLUSIONS: Metabolic response is at least as effective as anatomic response in predicting survival. Metabolic response may be an earlier predictive factor for treatment response and OS in NSCLC patients.

Voltage-gated sodium channel blockers can augment the efficacy of chemotherapeutics by their inhibitory effect on epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a process during which cancer cells become more invasive and chemo resistant. EMT may also be associated with tumor dormancy which prevents the cure of cancer with adjuvant treatment. Chemo resistance and dormancy may also decrease response to cytotoxic agents during treatment of metastatic disease. Voltage gated sodium channels (VGSCs) are overexpressed in many cancer types, particularly in those with more aggressive and metastatic potential. VGSCs are thought to be associated with increased invasive and migratory capacity of cancer cells. Inhibition of VGSCs may inhibit EMT and angiogenesis through interaction with intracellular calcium activity and endothelial cells respectively. Blockage of these channels combined with other anticancer therapies may be effective in both adjuvant and palliative setting. Colonization at secondary site may be decelerated by VGSCs inhibition through impeding angiogenesis. This may lead to a temporary palliation of symptoms related to tumor burden in patients with metastatic disease.

Should we be more cautious about replacement of vitamin B12 in patients with cancer receiving cytotoxic chemotherapy?

Vitamin B12 (Cbl) deficiency may cause hematologic and neurologic dysfunction. Replacement therapy is effective in correcting hematologic abnormalities and improving neurologic symptoms. Cbl is known to have antioxidant activity. This antioxidant activity may antagonize the effects of chemotherapeutics (i.e. genotoxic effects of paclitaxel) on tumor DNA. We claim that Cbl replacement should be done more cautiously in patients receiving cytotoxic chemotherapy.

Serum leptin level and waist-to-hip ratio (WHR) predict the overall survival of metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs).

INTRODUCTION: Our objective was to determine whether serum leptin levels and obesity-related factors could affect outcome for metastatic breast cancer (MBC) patients treated with aromatase inhibitors (AIs). METHODS: Sixty MBC patients treated with first line hormonal therapy were enrolled in this study. RESULTS: Median age was 51 years (range 28-75). Median leptin level was 19400 pg/ml (1970-91900) and estradiol level 29.6 pg/ml (4.0-181.9). Factors associated with overall survival in univariate analysis were age and waist-to-hip ratio (WHR), whereas only WHR retained significance in the multivariate analysis. However, no factor was associated with progression-free survival. However, WHR was found to be a significant prognostic marker only if the leptin level was ≥19400 pg/ml (HR = 0.38; 95% CI: 0.16-0.91). CONCLUSIONS: This study suggests that serum leptin levels and WHR together may serve as potential prognostic markers in MBC patients treated with AIs.

Chemotherapy-induced Hepatitis B virus reactivation in HbsAg positive cancer patients: a single center experience.

Hepatitis B reactivation due to chemotherapy is a cause of serious morbidity and mortality in some of the patients with cancer. In this study, we retrospectively assessed the prevalence of hepatitis B reactivation among the patients undergoing cytotoxic chemotherapy. We investigated efficacy of lamivudine prophylaxis against hepatitis B reactivation as well.