Clinical outcomes of concomitant use of proton pump inhibitors and regorafenib in patients with metastatic colorectal cancer: a multicenter study.

AIM: To compare survival outcomes, response rates, and adverse events (AEs) in proton pump inhibitor (PPI) user and non-user patients with metastatic colorectal cancer (mCRC) treated with regorafenib. METHODS: We included 272 patients with mCRC treated with regorafenib in this study. Patients were divided into two categories according to their status of PPI use. The primary endpoint was overall survival (OS). The secondary endpoints were time to treatment failure (TTF), response rates, and safety. To exclude immortal time bias in survival analyses, we compared PPI non-user patients and all patients. RESULTS: There were 141 and 131 patients in the PPI non-user and user groups. Baseline characteristics were similar in each group. Pantoprazole was the most used PPI. At the median 35.2 (95% confidence interval (CI): 32.6-37.9) months follow-up, the median OS was similar in PPI non-user and all patients (6.9 months (95% CI: 5.3-8.5) and 7.7 months (95% CI:6.6-8.8), p = 0.913). TTF was also similar in PPI non-user and all patients (3.3 months (95% CI: 2.7-3.9) and 3.5 months (95% CI: 3.0-4.0), p = 0.661). In multivariable analysis, no statistically significant difference was observed between PPI user and non-user groups in OS and TTF (hazard ratio (HR), 0.99; 95% CI, 0.77-1.28; p = 0.963 for OS; HR, 0.93; 0.77-1.20, p = 0.598 for TTF). The objective response rates (ORR) were similar in the PPI non-user and user groups (19.8% and 16.8%, p = 0.455). The rates of any grade AEs were also similar in each group. CONCLUSION: This study found no worse outcome in the combined use of PPI and regorafenib among patients with mCRC.

Efficacy and tolerability of current treatments for hormone-refractory prostate cancer patients with visceral metastases.

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

Lay abstract The optimal therapeutic option for castration-resistant prostate cancer (CRPC) patients with visceral metastases is unknown. We assessed the efficacy and tolerability of the first-line treatment options for CRPC patients with visceral metastasis. One hundred ninety-one patients diagnosed with CRPC with visceral metastases were included in the study. The present study established a statistically significant difference in favor of docetaxel in terms of overall survival and progression-free survival between first-line docetaxel, abiraterone and enzalutamide treatments in CRPC patients with visceral metastases. For patients who cannot undergo chemotherapy, enzalutamide, among novel androgen pathway inhibitors, may be the most appropriate option, given its numerical, although statistically insignificant, difference in overall survival and its fewer side effects compared with abiraterone.

Adjuvant Concurrent Chemoradiotherapy (CRT) plus Docetaxel-Cisplatin-Fluorouracil (DCF) versus CRT plus Fluorouracil-Folinic Acid (FUFA) in Stage III Gastric Cancer.

INTRODUCTION: Adjuvant chemoradiotherapy (CRT) is the optimal management strategy in resectable gastric cancer. There is a debate about the efficacy of more aggressive CRT plus chemotherapy regimens in adjuvant setting. This study aimed to compare the efficacy of adjuvant CRT plus docetaxel-cisplatin-fluorouracil (DCF) versus CRT plus fluorouracil-folinic acid (FUFA) in stage III gastric cancer. METHODS: Patients with a diagnosis of stage III gastric cancer treated with adjuvant therapy after curative resection were analyzed. Patients' disease characteristics and impacts of the regimens on median disease-free survival (DFS) and median overall survival (OS) were analyzed retrospectively. RESULTS: One hundred sixty-one patients (102 in FUFA arm and 59 in DCF arm) with a median age of 56.0 (29-79) were evaluated. In the DCF arm, there were more renal toxicities (31.6% vs 6.4% P < 0.001), emergency department admissions (64.9% vs 23.7%, P < 0.001), and dose reductions/treatment modifications in the DCF arm (51.6% vs 37.2, P < 0.001). The median follow-up was 23 months (1-124) in the FUFA arm and 26.0 months (1-77) in the DCF arm. The median DFS was 25.0 months (%95 CI, 12.7-37.2) in the DCF arm and 17.0 months (%95 CI, 2.6-31.3) in the FUFA arm, P = 0.66. The median OS was 28.0 months (%95 CI, 17.0-38.9) in the DCF arm and 25.0 months (%95 CI, 11.9-36.0) in the FUFA arm, P = 0.70. CONCLUSION: In conclusion, when compared with FUFA regimen, more aggressive therapy with DCF was more toxic and did not improve OS in adjuvant setting of stage III gastric cancer.

The impact of adjuvant oxaliplatin and tumor sidedness on the overall survival of stage IIB colon cancer patients: a multicentre study.

The aim of this multicentre retrospective study was to compare the efficacy of adjuvant chemotherapy regimens both with and without oxaliplatin and tumor sidedness in stage IIB (pT4aN0) colon cancer patients. This study included patients with stage IIB colon cancer who underwent curative surgery and received adjuvant chemotherapy. The patients were divided into two groups (one with and one without oxaliplatin) to compare the overall survival (OS) in right- and left-sided tumors. The study population included 298 patients with stage IIB colon cancer (median age: 57) of whom 69.1% were male. Forty-four per cent of these patients (n = 131) were diagnosed with right-sided colon cancer. The median follow-up duration was 35.9 months. In the entire population, a median OS was not reached, and the five-year OS was 83%. The median disease-free survival (DFS) was 12 months. There was no significant difference in terms of the five-year OS between right- (82%) and left-sided (84%) colon tumors (p = 0.67). In addition, the five-year OS of patients treated with and without oxaliplatin were 76% and 89%, respectively, and there was no statistically significant difference (p = 0.23). The five-year OS of the patients treated with and without oxaliplatin were 83% and 96.5%, respectively, (p = 0.8) in right-sided colon tumors, while it was 75% and 93% (p = 0.06), respectively, in left-sided colon tumors. Tumor sidedness and the addition of oxaliplatin to adjuvant chemotherapy were not found to be associated with the OS in stage IIB colon cancer patients in our study. Further large prospective studies that also include MSI, RAS and BRAF status data are warranted in colon cancer patients.

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

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

Effect of Adjuvant Chemotherapy in Stage III Cervical Cancer Patients Treated with Concurrent Chemoradiation: A Multicenter Study.

INTRODUCTION: A significant proportion of cervical cancer (CC) patients are diagnosed at a locally advanced stage. Concurrent chemoradiotherapy (CCRT) is the cornerstone of treatment for patients with locally advanced CC. However, the role of adjuvant chemotherapy (AC) after CCRT is controversial. In this study, we analyzed the efficacy of AC after CCRT in stage III CC patients. METHODS: We performed a multicenter, retrospective analysis of 139 International Federation of Gynecology and Obstetrics stage III CC patients treated with CCRT of whom 45.3% received AC. Our goal was to determine the impact of AC on survival in these patients. RESULTS: Five-year progression-free survival (PFS) was 37.5% and 16% in patients receiving CCRT with and without AC, respectively (p = 0.008). Median PFS was 30.9 months (CI 95% 14.8-46.9) and 16.6 months (CI 95% 9.3-23.9) in patients receiving CCRT with and without AC, respectively. Five-year overall survival (OS) was 78.2% and 28.4% in patients receiving CCRT with and without AC, respectively (p < 0.001). Median OS was 132.2 months (CI 95, %66.5-197.8) and 34.9 months (CI 95% 23.1-46.7) in patients receiving CCRT with and without AC, respectively. CONCLUSION: Our study suggests that AC provides OS and PFS benefit in stage III CC patients. Larger studies are needed to identify subgroups of patients who would benefit from AC.

Assessment of Prognostic Factors and Adjuvant Treatment Modalities in Adult Head and Neck Soft Tissue Sarcoma Patients Treated With Upfront Surgery.

Objectives Head and neck soft tissue sarcomas (HNSTSs) are a heterogeneous group of rare tumors. Surgical resection with negative margins remains the standard primary treatment for patients with HNSTS. The role of chemotherapy (CT) and radiotherapy (RT) remains controversial. In this multicenter study, we aimed to demonstrate the real-world assessing prognostic factors and the effect of adjuvant treatment modalities in adult patients with HNSTS treated with upfront surgery. Methods We included a total of 47 patients who underwent curative-intent resection of a primary HNSTS between 2000 and 2019. Results The median follow-up was 29 months. The median age of patients was 51 years, and 66% of patients were male. The median relapse-free survival (RFS) of the study population was 31 months (range: 1.0-61.1 months), and the median overall survival (OS) was 115 months (range: 60.8-169.2 months). The univariable analysis revealed that treatment modalities showed a significant impact on RFS (p = 0.021); however, no difference was found in its impact on OS (p = 0.137). R0 resection did not showed impact on RFS (p = 0.130), but a significant association was found with OS (p = 0.004). In multivariable analysis, T stage of the tumor (hazard ratio [HR]: 3.834; 95% CI: 1.631-9.008; p = 0.002) and treatment with surgery and sequential RT and CT (HR: 0.115; 95% CI: 0.035-0.371; p < 0.001) were independent factors associated with RFS. R0 resection was independently associated with OS (HR: 4.902; 95% CI: 1.301-18.465; p = 0.019). Conclusion Our study revealed that R0 resection improved OS, and T3-4 stage of tumor was a negative independent factor for RFS in surgically resected HNSTS patients. The use of sequential CT and RT after resection was associated with a better RFS, which emphasizes the importance of multidisciplinary evaluation of the treatment of HNSTS. Randomized prospective studies are needed.

Untargeted multi-omic analysis of colorectal cancer-specific exosomes reveals joint pathways of colorectal cancer in both clinical samples and cell culture.

Exosomes are naturally secreted nano-vesicles consisting of biochemical molecules including RNAs, metabolites, lipids, and proteins, that emerge as diagnostic tools and disease-specific reporters. Here we offer a systematic and integrative approach for the simultaneous analysis of altered molecules namely metabolites, lipids, and proteins. These components tend to augment the discovery of low abundance signature components, and assist in explanation of molecular basis of colorectal cancer (CRC). In order to investigate CRC-derived exosomes, we selected mi-R19a, miR-21, miR-92a, and miR-1246 positive exosomes for downstream experiments. The overall multi-omic changes were investigated comparatively in cell culture and serum samples. Following a systematic multi-omic study, 37 (cell culture) and 31 (serum) metabolites; 130 (cell culture) and 56 (serum) lipids; 9 (cell culture) and 13 (serum) proteins were seen to be differentially expressed (p < 0.05), enabling discrimination between CRC and control. By using these enriched components, we demonstrated that the joint pathways mainly involving fatty acid and amino acid metabolism related pathways changed in CRC significantly. We conclude that this study increases our understanding of molecular basis of CRC, and provides potential exosomal biomarkers for the non-invasive detection, and discrimination of CRC.