Introduction: Systemic inflammation is associated with prognosis in solid tumors. The neutrophil-to-lymphocyte ratio (NLR) is a marker for the general immune response to various stress stimuli. Studies have shown correlation of NLR to outcomes in immune checkpoint blockade, peripheral neutrophil count to intratumor neutrophil population, and NLR to intratumoral levels of myeloid-derived suppressor cells. Studies have shown elevated peripheral blood regulator T cells accompanied by elevated NLR are associated with poor outcomes further highlighting the importance of inflammation in the prognosis of cancer patients. Methods: We performed a meta-analysis of published articles on the utility of baseline NLR in predicting outcomes in patients treated with immune checkpoint inhibitors (ICIs) using Review Manager, version 5.3. Seven studies on the prognostic utility of NLR in ICI treatment were included in this analysis. For outcomes of interest, the hazard ratios (HRs) were computed. Subgroup analyses were planned based on type of malignancy and type of immune checkpoint inhibitor. Results/discussion: A high NLR resulted in worse overall survival (OS) (HR, 1.92; 95% CI, 1.29–2.87; p=0.001) and progression-free survival (PFS; HR, 1.66; 95% CI, 1.38–2.01; p<0.00001) across types of malignancies studied (melanoma, non-small-cell lung cancer, and genitourinary cancer). Subgroup analysis across different types of malignancies treated with ICI showed similar results for OS and PFS. The single study on genitourinary cancers also showed worse OS and PFS (OS: HR, 1.82; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.83; 95% CI, 0.97–3.44; p=0.06). A high NLR also showed worse OS and PFS across all ICIs (ipilimumab, nivolumab, and unspecified or pooled pembrolizumab and nivolumab; OS: HR, 1.92; 95% CI, 1.29–2.87; p=0.001 and PFS: HR, 1.66; 95% CI, 1.38–2.01; p<0.00001). Subgroup analysis by type of ICI showed similar results. Conclusion: A high NLR is associated with poorer outcomes across studies. This shows that NLR has the potential as a readily available prognostic indicator for patients receiving ICI based on available studies. Studies utilizing more stringent design may serve to better determine the utility of this tool.

Evasion of immune destruction is considered one of the hallmarks of cancer. Chronic inflammation can enable immune escape by suppressing immune surveillance and permitting the development of tumors and creating a tumor microenvironment that sustains cancer. This includes generating mechanisms that prevent the effectiveness of anti-tumor treatment including immune checkpoint inhibitor therapy. In this review, we explore the interplay of inflammation and immunosuppression, their effects on the tumor microenvironment, and their implications for immune checkpoint inhibitor therapy particularly in the context of predictive biomarkers for their use.

Small-cell lung cancer (SCLC) methylome is understudied. Here, we comprehensively profile SCLC using cell-free methylated DNA immunoprecipitation followed by sequencing (cfMeDIP-seq). Cell-free DNA (cfDNA) from plasma of 74 patients with SCLC pre-treatment and from 20 non-cancer participants, genomic DNA (gDNA) from peripheral blood leukocytes from the same 74 patients, and 7 accompanying circulating tumor cell-derived xenografts (CDXs) underwent cfMeDIP-seq. Peripheral blood leukocyte methylation (PRIME) subtraction to improve tumor specificity. SCLC cfDNA methylation is distinct from non-cancer but correlates with CDX tumor methylation. PRIME and k-means consensus identified two methylome clusters with prognostic associations that related to axon guidance, neuroactive ligand−receptor interaction, pluripotency of stem cells, and differentially methylated at long noncoding RNA and other repeats features. We comprehensively profiled the SCLC methylome in a large patient cohort and identified methylome clusters with prognostic associations. Our work demonstrates the potential of liquid biopsies in examining SCLC biology encoded in the methylome.

PURPOSE: Cancer treatment causes significant financial burden, especially in developing countries such as the Philippines. This led the Philippine Department of Health to create the Z-Package colorectal cancer benefit program, an insurance system specifically designed to treat Filipinos with colorectal cancers with early to locally advanced-stage disease. The main goal of this program is to optimize treatment outcomes for this curable disease without causing financial toxicity. MATERIALS AND METHODS: Three-year data on patients enrolled in the Z-Package colorectal cancer benefit program from 2016 to 2018 were reviewed by the University of the Philippines, Philippine General Hospital Colorectal Polyp and Cancer Study Group. RESULTS: A total of 251 patients were enrolled in the Z-package colorectal cancer benefit program from 2016 to 2018. Mean age was 57 years old and a majority of patients (66%) were male. A majority of patients had rectal cancer (78%) and were diagnosed with stage III disease (82%). A majority (75%) were compliant to their treatment plans and clinic follow-up. Specifically, compliance to the prescribed surgery, chemotherapy, and/or radiation treatment were 90%, 77%, and 96%, respectively. Recurrence, morbidity, and mortality rates of enrolled patients in the Z-Package program from 2016 to 2018 were 17%, 22%, and 19%, respectively. Morbidities were mostly chemotherapy related (8%). Finally, patients in this program had a 2- and 3-year survival probability of 74% and 70%, respectively, which are comparable with data from more developed nations. CONCLUSION: Results of this study include real-world data that show that when the highest standards of patient care are provided through a multidisciplinary team, patients’ overall survival is also maximized.

Introduction: Young-onset colorectal cancer is recognized as a distinct disease that may be sporadic or hereditary in nature. Microsatellite instability testing is recommended as a routine procedure in evaluating colorectal cancer specimens, especially in young-onset disease, because of implications in management. Immunohistochemistry of mismatch repair proteins serves as an inexpensive alternative to microsatellite instability testing with the added advantage of monitoring protein expression levels that may suggest underlying genetic or epigenetic alterations. This descriptive study aimed to determine the frequencies of proficient and deficient mismatch repair status among Filipino young-onset colorectal cancer patients, and to investigate their clinicopathologic profile. Methods: Tumor tissues were prospectively collected from patients from two tertiary hospitals in the Philippines. Patients of age ≤ 45 years with resected adenocarcinoma of the colon or rectum were recruited. Results: Seventy-seven out of 124 patients had tumor samples sent for immunohistochemistry. Of these, 61 samples (79%) were found to have proficient status while 16 samples (21%) had deficient status. Mismatch repair protein deficiencies, when present, more commonly involved MSH2 and MSH6 (9%) rather than MLH1 and PMS2 (5%). The deficient group had a mean age of 37.1 years and a female preponderance (56.25%), presenting as locally advanced ascending or descending colon tumors with mucinous histology in half of the population. The mismatch repair proficient group presented as locally advanced rectal and sigmoid tumors but with fewer mucinous adenocarcinomas (26.2%) compared to the deficient group. In both the mismatch repair proficient and deficient patients with family history reports, most did not have any known relative with cancer (75.4% and 68.75%, respectively). Conclusion: This is the first attempt to perform mismatch repair testing among young-onset colorectal cancer patients in the Philippines and to gather data on their clinicopathologic characteristics. However, the limited sample size precludes conclusive results for the associations of mismatch repair with clinicopathologic features.

Treatment of cancer patients during the COVID-19 pandemic in the Philippines Frederic Ivan Ting1a, Danielle Benedict Sacdalan1b, Honey Sarita Abarq