Impact of perioperative chemotherapy on survival in patients with cholangiocarcinoma undergoing curative resection.

BACKGROUND: Most patients with localized cholangiocarcinoma (CCA) endure cancer relapse after curative resection underscoring the importance of systemic therapy. The current study attempts to determine the impact of perioperative chemotherapy (PC) on survival in patients with CCA undergoing resection. METHODS: Patients diagnosed with CCA undergoing curative-intent resection between January 1, 2000, and December 31, 2019, in a tertiary care center were included. Cox proportional hazard modeling was used to determine the impact of PC on disease-free survival (DFS) and overall survival (OS). In addition, a nomogram was constructed to estimate 3-year DFS. RESULTS: Among the 182 patients included in the analysis, 102 underwent surgery alone, and 80 received surgery plus PC. Forty-two patients received neoadjuvant therapy, and 38 patients received adjuvant therapy. On multivariate analysis, PC was significantly associated with an improved DFS (HR, 95% CI: 0.63, 0.41-0.98; p = 0.04) and OS (HR, 95% CI: 0.46, 0.27-0.78; p < 0.01). In the interaction analysis, the survival benefit was especially seen in patients with positive resection margins and tumor size > 5 cm. CONCLUSION: In patients with CCA undergoing curative resection, receipt of PC was associated with improved DFS and OS. The nomogram constructed from this database provides an estimate of 3-year DFS after surgical resection. Randomized trials are needed to define the optimal regimen and sequence.

Outcomes following FGFR Inhibitor Therapy in Patients with Cholangiocarcinoma.

BACKGROUND: Sequencing efforts in patients with cholangiocarcinoma (CCA) have provided insights into molecular mechanisms including fibroblast growth factor receptor (FGFR) alterations. There is a lack of data on outcomes of patients following cessation of FGFR inhibitor (FGFRi) therapy. OBJECTIVE: We describe the clinical outcomes following initial FGFRi treatment in CCA harboring FGFR alterations. PATIENTS AND METHODS: We conducted a multicentric, retrospective analysis of patients with FGFR-altered CCA diagnosed between 2010 and 2021. Median overall survival (OS) and progression-free survival (PFS) analyses were performed using the Kaplan-Meier method. RESULTS: We identified 88 advanced or metastatic CCA patients, 28 males (31.8%) and 60 females (68.2%), harboring FGFR alterations who received FGFRi. Median PFS on initial FGFRi was 6.6 months (95% confidence interval (CI): 5.5-8.3). Following cessation of first FGFRi therapy, 55% patients received systemic therapy as next line: 67% received chemotherapy or targeted treatment and 33% received another FGFRi. Median PFS for patients who received chemotherapy or targeted agent was 2.1 months (95% CI 1.6-5.7) and for patients who received a second FGFRi was 3.7 months (95% CI 1.5-not evaluable). OS was 2.0 months for patients who did not receive any therapy compared to 8.7 months with chemotherapy and 8.6 months with another FGFRi. In addition, one patient treated with pemigatinib developed FGFR2 M540_I541insMM alteration at time of resistance, which has not been functionally characterized and its effect on protein function remains unknown. CONCLUSIONS: Understanding the mechanisms of resistance with FGFRi is essential to understand sequencing of treatments. In this study, patients received standard chemotherapy in the first line and were fit enough to be considered for subsequent therapy with an FGFRi. Almost half of the patients become ineligible to receive further systemic therapy following progression on FGFRi. As more agents are being introduced, detailed understanding of outcomes following treatment with an FGFRi, including subsequent FGFRi, is essential.

Tumor Mutational Burden Is a Potential Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients With Advanced Biliary Tract Cancer.

PURPOSE: Patients with advanced biliary tract cancers (BTCs) have a dismal prognosis. This multisite, single-institution study analyzed the efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with advanced BTC. MATERIALS AND METHODS: The prospectively maintained institutional database was searched for patients with advanced BTC. Electronic medical records of the patients with advanced BTC treated with an ICI that included programmed death-1 or programmed death-ligand 1 blockers were retrospectively reviewed to obtain data on patient characteristics, tumor characteristics including molecular biomarkers, detailed treatment, response characteristics, survival, and toxicities. The analysis included overall response rate, survival, and correlation between survival and molecular biomarkers. RESULTS: The institutional database query identified 47 patients with advanced BTC who received at least one dose of an ICI; 11 (24%) patients in the first-line setting and the rest of the patients had refractory disease. The median age of the cohort was 62 years, and 51% were female. The overall response rate was 10.6%, with a disease control rate of 53.2%. The median progression-free survival (PFS) and overall survival were 3.6 months and 6.9 months, respectively. Biomarker analysis revealed improved PFS in patients with tumor mutational burden > 5 mutations per megabase (median PFS: 6.4 v 2.2 months; P = .0027). No unexpected adverse events were observed. CONCLUSION: ICIs are well tolerated and have modest antitumor activity in patients with advanced BTC. The study result supports the exploration of tumor mutational burden as a potential predictive biomarker for response to ICIs in patients with advanced BTC.

Update on the role of pembrolizumab in patients with unresectable or metastatic colorectal cancer.

Colorectal cancer (CRC) is the third most common cancer type in both men and women in the USA. Most patients with CRC are diagnosed as local or regional disease. However, the survival rate for those diagnosed with metastatic disease remains disappointing, despite multiple treatment options. Cancer therapies for patients with unresectable or metastatic CRC are increasingly being driven by particular biomarkers. The development of various immune checkpoint inhibitors has revolutionized cancer therapy over the last decade by harnessing the immune system in the treatment of cancer, and the role of immunotherapy continues to expand and evolve. Pembrolizumab is an anti-programmed cell death protein 1 immune checkpoint inhibitor and has become an essential part of the standard of care in the treatment regimens for multiple cancer types. This paper reviews the increasing evidence supporting and defining the role of pembrolizumab in the treatment of patients with unresectable or metastatic CRC.

HPV Status and Survival in Non-Oropharyngeal Squamous Cell Carcinoma of the Head and Neck.

BACKGROUND/AIM: HPV-mediated oropharyngeal squamous cell carcinoma is associated with an increased survival. The prognostic value of HPV status for other primary sites is unclear. We aimed to assess the effect of HPV status on overall survival in patients with non-oropharyngeal head and neck squamous cell carcinoma (non-OPSCC) using the National Cancer Database (NCDB). PATIENTS AND METHODS: Adults with non-OPSCC [gum, lip, floor of mouth, tongue (excluding base), hypopharynx, nasopharynx, other pharynx] and known HPV status were included in our study. Associations between HPV status, primary site, patient characteristics and overall survival (OS) were assessed. RESULTS: HPV positivity was associated with a better OS compared to HPV-negative patients (HR=0.83, 95%CI=0.74-0.93, p<0.001). Female gender, gum, lip, nasopharynx primaries, and private insurance predicted for improved OS. CONCLUSION: HPV positivity and female gender are good prognostic factors in non-OPSCC. Routine HPV testing should be considered for HPV positive non-OPSCC, as well as studies evaluating de-escalation of treatment if this association is confirmed.

Evaluating Symptom Distress in Cancer Patients.

BACKGROUND: Distress in cancer patients negatively affects emotions and coping abilities and can reduce treatment adherence, quality of life, and survival rates. The prevalence of distress in cancer patients has been reported at 35.1 percent and 37.8 percent, but is frequently undiagnosed. Previous studies have produced conflicting results regarding reported symptoms.This study aims to help health care providers identify symptoms correlated with distress to improve recognition and treatment. METHODS: A cross-sectional study was performed via medical record review of 40 adult cancer patients at the Avera Cancer Institute. Responses were compared using Pearson's chi-square test and the t-test. RESULTS: The average age of participants was 56.8 ± 12.0, and 65 percent had breast cancer. The mean overall score for distress was 4.6 ± 2.7 points on a 0-10 scale (95 percent CI 3.71 - 5.45). Twenty-four patients (60 percent) reported clinically significant distress. Females were more likely to report sadness. Specific symptoms with a statistically significant association with a higher overall distress included: fears, depression, sleep, worry, fatigue, nervousness, eating, and loss of interest in normal activities. CONCLUSIONS: Although our sample size was small and homogeneous, the results demonstrated statistically significant associations between overall distress and the symptoms of fears, depression, sleep, worry, fatigue, nervousness, eating, and loss of interest in normal activities. These findings can increase awareness of symptoms associated with distress and allow clinicians to recommend specific interventions. Though many oncology clinics screen for distress, distress remains an important factor affecting quality of life and warrants further investigation.