Steven E Kalloger

Univariable DSS according to immune biomarkers. Kaplan–Meier curves show DSS stratified by (A) PD-L1 CPS 0 vs. ≥1; (B) PD-L1 CPS <10 vs. ≥10; (C) dMMR vs. pMMR; (D) intraepithelial CD3+ T-cell presence vs. absence; (E) intraepithelial CD8+ T-cell presence vs. absence; (F) stromal CD3+ T-cell counts categorized as low vs. high; (G) intraepithelial CD3+ T-cell counts categorized as low vs. high; (H) stromal CD8+ T-cell counts categorized as low vs. high; and (I) intraepithelial CD8+ T-cell counts categorized as low vs. high. High vs. low count categories were defined using the cohort mean for each marker and compartment (CD3: 56 cells in stroma and 11 cells in epithelium; CD8: 27 cells in stroma and 5 cells in epithelium). Numbers at risk are displayed within each panel. P values are from two-sided log-rank tests. Epi, epithelium; Str, stroma.

Prevalence of descriptive MMR/CD8 phenotypes among 98 tumors with both markers evaluable. dMMR was assigned regardless of CD8 localization; inflamed pMMR denotes pMMR with intraepithelial CD8+ T-cell presence; and noninflamed pMMR denotes pMMR without intraepithelial CD8+ T-cell presence. The categories are descriptive and are not treatment-selection classes.

Table 1 from Compartment-Specific CD8 Infiltration and Disease-Specific Survival in Resected Ampullary Adenocarcinoma

Likelihood-ratio P values for biomarker associations with pathology variables.

Exploratory adjusted associations between TIL measures and DSS.

Ampullary adenocarcinoma is rare, and its immune biomarker landscape is incompletely characterized. This article evaluated mismatch repair (MMR), programmed cell death ligand 1 (PD-L1; CD274), and compartment-specific CD3 (CD3E)/CD8 (CD8A) tumor-infiltrating lymphocytes (TIL) in resected tumors and explored associations with disease-specific survival (DSS). Ninety-nine patients underwent pancreaticoduodenectomy at Vancouver General Hospital (VGH) between 1984 and 2013. Duplicate 0.6-mm tissue microarrays (TMA) were assessed for MMR proteins, PD-L1 combined positive score (CPS), and stromal and intraepithelial CD3 and CD8 counts. DSS was estimated using the Kaplan–Meier method. Exploratory Cox models were adjusted for age, histologic subtype, pathologic tumor (pT) group, pathologic node (pN) status, and adjuvant chemotherapy. There were 44 DSS events. MMR deficiency (dMMR) was present in 37 of 99 (37.4%) tumors. PD-L1 was evaluable in 87 tumors; 57 of 87 (65.5%) tumors had CPS ≥1, and 24 of 87 (27.6%) tumors had CPS ≥10. Intraepithelial CD8+ T cells were present in 23 of 98 (23.5%) tumors. PD-L1 CPS ≥1, PD-L1 CPS ≥10, and MMR status were not associated with DSS by log-rank testing (P = 0.35, P = 0.98, and P = 0.74, respectively). In the pT-adjusted model, intraepithelial CD8 presence was associated with lower disease-specific hazard [hazard ratio (HR), 0.422; 95% confidence interval (CI), 0.144–0.994; likelihood-ratio P = 0.048], although the Wald sensitivity test was not significant (P = 0.074). Continuous log-transformed intraepithelial CD8 counts showed a concordant, method-dependent signal. dMMR and PD-L1 expression were common in this historical resected cohort. Intraepithelial CD8 infiltration was associated with DSS, but the borderline and inferential method–dependent estimates require external validation. These prognostic data do not establish benefit from immune checkpoint blockade. Significance:Ampullary cancer is a rare disease in which treatment is extrapolated from other gastrointestinal cancers. In this cohort, immune features varied among tumors with functioning MMR. CD8+ T cells within the tumor epithelium showed an exploratory association with improved DSS, which supports the prospective evaluation of immune stratification, not immediate treatment selection.

Ampullary adenocarcinoma is rare, and its immune biomarker landscape is incompletely characterized. This article evaluated mismatch repair (MMR), programmed cell death ligand 1 (PD-L1; CD274), and compartment-specific CD3 (CD3E)/CD8 (CD8A) tumor-infiltrating lymphocytes (TIL) in resected tumors and explored associations with disease-specific survival (DSS). Ninety-nine patients underwent pancreaticoduodenectomy at Vancouver General Hospital (VGH) between 1984 and 2013. Duplicate 0.6-mm tissue microarrays (TMA) were assessed for MMR proteins, PD-L1 combined positive score (CPS), and stromal and intraepithelial CD3 and CD8 counts. DSS was estimated using the Kaplan–Meier method. Exploratory Cox models were adjusted for age, histologic subtype, pathologic tumor (pT) group, pathologic node (pN) status, and adjuvant chemotherapy. There were 44 DSS events. MMR deficiency (dMMR) was present in 37 of 99 (37.4%) tumors. PD-L1 was evaluable in 87 tumors; 57 of 87 (65.5%) tumors had CPS ≥1, and 24 of 87 (27.6%) tumors had CPS ≥10. Intraepithelial CD8+ T cells were present in 23 of 98 (23.5%) tumors. PD-L1 CPS ≥1, PD-L1 CPS ≥10, and MMR status were not associated with DSS by log-rank testing (P = 0.35, P = 0.98, and P = 0.74, respectively). In the pT-adjusted model, intraepithelial CD8 presence was associated with lower disease-specific hazard [hazard ratio (HR), 0.422; 95% confidence interval (CI), 0.144–0.994; likelihood-ratio P = 0.048], although the Wald sensitivity test was not significant (P = 0.074). Continuous log-transformed intraepithelial CD8 counts showed a concordant, method-dependent signal. dMMR and PD-L1 expression were common in this historical resected cohort. Intraepithelial CD8 infiltration was associated with DSS, but the borderline and inferential method–dependent estimates require external validation. These prognostic data do not establish benefit from immune checkpoint blockade. Significance: Ampullary cancer is a rare disease in which treatment is extrapolated from other gastrointestinal cancers. In this cohort, immune features varied among tumors with functioning MMR. CD8+ T cells within the tumor epithelium showed an exploratory association with improved DSS, which supports the prospective evaluation of immune stratification, not immediate treatment selection.

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Cancer-related fatigue (CRF) continues to be a challenging phenomenon that is often underreported and poorly understood. With etiologies in both disease and treatment manifesting as a symptom and a side effect, respectively, CRF is highly incident and presents a significant clinical problem that impacts survivorship. We conducted a survey to ascertain the patient-reported incidence of symptoms and side effects for people with lymphoma or chronic lymphocytic leukemia. We found that CRF was enhanced in those who received more intense therapies that coincided with more aggressive lymphoma subtypes. These data illuminate an unmet need among patients with lymphoma and provide an opportunity to further refine treatment regimens in order to reduce the burden of CRF in this vulnerable population. Significance: CRF is a highly incident phenomenon in lymphoma that can be ascribed to a combination of causes. We have demonstrated substantial variability across various subtypes of lymphoma and have estimated that nearly half of the reported fatigue comes from treatment. Increased screening for and monitoring of fatigue will yield favorable health-related quality of life that will benefit health technology assessment activities and yield improved outcomes for patients.

The effect of age and biological sex on the probability of experiencing CRF as a symptom, side effect or both. Panels A and B demonstrate that for patients with DLBCL, the probability of experiencing CRF as both a symptom and side effect increases by a factor of 1.37 for females relative to males given a static age of 50 years. Panels C and D demonstrate a similar but milder phenomenon for patients with follicular lymphoma. Increasing age was also associated with experiencing CRF as both a symptom and side effect. In contrast, the way CRF was experienced by patients with mantle cell lymphoma was not influenced by biological sex but rather age. A 30 year increase in age saw the probability of experiencing CRF as both a symptom and a side-effect increase by a factor of 2.21 (E and F).