Background: Sarcopenia and inflammation are independently associated with worse survival in cancer patients. This study aims to determine the impact of sarcopenia, body mass index (BMI), and inflammatory biomarkers on survival in advanced hepatocellular carcinoma (HCC) patients treated with anti-PD-1 antibody-based immunotherapy. Methods: A retrospective review of advanced HCC patients treated with immunotherapy at Winship Cancer Institute between 2015 and 2019 was performed. Baseline computed tomography and magnetic resonance images were collected at mid-L3 level, assessed for skeletal muscle density using SliceOmatic (TomoVision, version 5.0) and converted to skeletal muscle index (SMI) by dividing it by height (m2). Sex-specific sarcopenia was defined by the median value of SMI. The optimal cut for continuous inflammation biomarker was determined by bias-adjusted log-rank test. Overall survival (OS) was set as primary outcome and Cox proportional hazard model was used for association with survival. Results: A total of 57 patients were included; 77.2% male, 52.6% Caucasian, 58.5% Eastern Cooperative Oncology Group performance status 0-1, 80.7% Child Pugh A. Treatment was second line and beyond in 71.9% of patients. The median follow-up time was 6 months. Sarcopenia cut-off for males and females was SMI of 43 and 39, respectively. 49.1% of patients had sarcopenia. Median OS was 5 versus 14.3 months in sarcopenic versus nonsarcopenic patients (Log-rank P=0.054). Median OS was 5 and 17.5 months in patients with BMI <25 and BMI ≥25, respectively (Log-rank P=0.034). Median OS was 3.6 and 14.3 months for patients with neutrophil-to-lymphocyte ratio (NLR) ≥5.15 versus NLR <5.15 (Log-rank P<0.001). In multivariable Cox regression model, higher baseline NLR was associated with worse OS (hazard ratio [HR]: 4.17, 95% confidence interval [CI]: 1.52-11.39, P=0.005). Sex-specific sarcopenia showed a trend of worse OS (HR: 1.71, 95% CI: 0.73-4.00, P=0.215) but was not statistically significant. BMI<25 was associated with worse OS (HR: 2.28, 95% CI: 0.92-5.65, P=0.076). In the association with progression free survival, neither baseline BMI nor sex-specific sarcopenia showed statistical significance. Conclusion: After controlling for baseline Child Pugh score and NLR, sex-specific sarcopenia does not predict OS. Baseline BMI and NLR together may predict OS in advanced HCC patients treated with anti-PD-1 antibody.

Background. Immune checkpoint inhibitor (ICI) therapy is highly effective in metastatic mismatch repair-deficient (MMR-D) colorectal cancer (CRC). In this study, we evaluated molecular and clinical predictors of ICI response in MMR-D CRC. Patients and Methods. Patient databases at 4 cancer institutions were queried. The Fisher exact test was performed to test the association of clinical and molecular markers. The Kaplan-Meier method was used to estimate progression free survival (PFS) and compared by the log-rank test. Twelve-and 24-month PFS rates were compared by the Z test. Results. A total of 60 CRC patients with MMR-D/MSI-H who previously received ICI were identified. Patients with liver metastasis had a lower overall response rate (ORR) as compared to other sites of metastasis (36.4% vs 68.7%; P=0.081). Patients with MLH1/ PMS2 loss had worse 1-year and 2-year PFS rates compared to patients with MSH2/ MSH6 loss (84.2% vs 57.8% and 78.2% vs 54.2%, respectively; p<0.001). There were improved 1-year and 2-year PFS rates in patients with wild-type BRAF when compared to patients with BRAF V600E mutation (73.3% vs 40%, and 73.3% vs 26.7%; respectively [P<0.001]). Patients aged >65 had significantly worse PFS rates as compared to patients aged ≤ 65 (P<0.001). Conclusion. BRAF V600E mutation, MLH1 and/or PMS2 loss, as well as age >65 years and liver metastasis may be predictive of duration of ICI response in MMR-deficient CRC patients. Larger cohorts are needed to confirm our findings. The Oncologist 2021;9999:• • Implications for Practice: This results of this original research article reveals clinically important biomarkers that potentially predict immune checkpoint inhibitor response in mismatch repair deficient colorectal cancer patients.

119 patients (59%) who received at least a quarter of their ICI infusions in the morning had significantly longer OS (median 58 vs. 34 months, HR 0.51, 95% CI 0.29-0.89, P=0.017), independent of age, sex, RCC histology, liver and brain metastases, pre-treatment LDH, and choice of initial ICI; table 2, figure 1. Conclusions Patients with metastatic RCC may benefit from earlier time-of-day ICI infusions. Our findings are consistent with established mechanisms of chrono-immunology, as well as with preceding analogous studies in melanoma and lung cancer. Additional prospective randomized trials are warranted.

BackgroundThe NAPOLI-1 trial demonstrated that liposomal irinotecan in combination with fluorouracil (5-FU) and leucovorin (LV) prolonged survival with a manageable safety profile in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) previously treated with gemcitabine-based therapy. Real-world data on clinical outcomes associated with liposomal irinotecan in NAPOLI-1-based regimens is needed to further substantiate this.MethodsThis real-world, retrospective chart review study included patients with mPDAC who received NAPOLI-1-based regimens from six academic centers in the United States. Liposomal irinotecan initiation defined the index date. Overall survival (OS) and progression-free survival (PFS) were assessed with Kaplan-Meier methodology.ResultsThere were 374 patients evaluated; median age was 68 years, and 51% were female. Among 326 patients with baseline ECOG information, approximately 74% had ECOG score &lt;2. Liposomal irinotecan was administered as a doublet with 5-FU in a NAPOLI-1-based regimen in the first line (1L; 16%), 2L (42%), and 3L+ (42%) of the metastatic setting. For patients treated in 1L, 2L, and 3L+, median [95% confidence interval (CI)] OS was 8.0 [5.1, 11.2], 7.3 [5.3, 8.8], and 4.6 [4.0, 5.7] months, and median [95% CI] PFS was 4.2 [2.2, 6.6], 3.0 [2.6, 3.7], and 2.0 [1.7, 2.2] months, respectively.ConclusionsPatients in a real-world setting treated with NAPOLI-1-based liposomal irinotecan doublet regimens at academic centers were older with poorer performance status compared to trial patients yet had similar outcomes and efficacy. Furthermore, liposomal irinotecan was frequently used in the 3L+ setting where no treatment has been approved and provided clinical benefit.

Immunotherapy treatments in oncology have garnered much attention and use throughout the past several years. With increased use and new approvals in many different types of solid tumors and hematological malignancies, practitioners in oncology should have an appreciation and understanding of the potential adverse effects of these unique treatment approaches. The most common adverse effects with immunotherapy treatment are immune-related adverse effects with activation of patients' immune systems against a wide array of tissues and organ systems. Immune-related adverse effects are typically treated first with high doses of immunosuppressive corticosteroids. Patients with immune-related adverse effects refractory to high dose corticosteroid treatment may receive anti-tumor necrosis factor α therapy in an attempt to halt the immune system from causing further organ dysfunction. However, these agents are not always successful and other immunomodulatory agents should be considered for refractory cases. Presented here are three patient cases supporting the use of the calcinuerin inhibitor tacrolimus to treat immune-related adverse effects refractory to corticosteroids and anti-tumor necrosis factor α.