Lymphocyte-Sparing Radiotherapy: The Rationale for Protecting Lymphocyte-rich Organs When Combining Radiotherapy With Immunotherapy.

Serum markers associated with treatment response and survival in non-small cell lung cancer patients treated with anti-PD-1 therapy.

The present study aimed to determine the correlation between controlling nutritional status (CONUT) and prognosis in resected breast cancer patients. Totally, 861 breast cancer patients with surgical resection in West China Hospital of Sichuan University between 2007 and 2010 were included. The relationship between CONUT and various clinicopathological factors as well as prognosis was evaluated. The results showed that the optimal cutoff value for CONUT to predict the 5-year survival was 3 and CONUT had a higher area under the ROC curve (AUC) for 5-year disease free survival (DFS) and overall survival (OS) prediction compared with the neutrophil lymphocyte ratio (NLR) and prognostic nutritional index (PNI). High CONUT was significantly correlated with older age, lymph node involvement, advanced T-stage, and surgery type. In the multivariate analysis, CONUT-high patients had worse DFS and OS, when compared with CONUT-low patients. In conclusion, preoperative CONUT is a useful marker for predicting long term outcomes in breast cancer patients after curative resection.

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Controlling Nutritional Status (CONUT) score is a prognostic factor in patients with resected breast cancer.

Purpose We hypothesized that radiation-induced lymphopenia could be predicted by the effective dose to the circulating immune cells (EDIC) in advanced esophageal squamous cell carcinoma treated with trimodality therapy according to the Dutch ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial regimen. To test this hypothesis, we examined the effect of EDIC on the degree of lymphocyte drop (lymphocyte nadir). Methods and Materials Patients with advanced nonmetastatic esophageal squamous cell carcinoma treated in a single tertiary cancer center from 2012 to 2018 were eligible for this study. All patients had to have a radiation therapy plan available for EDIC computation and received neoadjuvant chemoradiation according to the Dutch CROSS trial regimen before radical esophagectomy. The EDIC was calculated as a function of integral doses to the lung, heart, and total body with a verified mathematical model. The association between EDIC and lymphocyte nadir was studied, and the relationships of overall survival (OS) with lymphocyte nadir and EDIC were assessed using multivariable Cox regression model. Results This analysis included 92 eligible consecutive patients (77 men and 15 women). The mean EDIC was 2.8 Gy (range, 0.6-4.4). EDIC was significantly correlated with lymphocyte nadir (Spearman coefficient = –0.505; P 4 Gy). The 2–year OS rates were 66.7%, 42.7%, and 16.7% for EDIC 4 Gy, respectively. Conclusions There was a significant correlation between radiation dose to circulating immune cells and lymphocyte nadir, which in turn affected OS in patients with advanced nonmetastatic esophageal squamous cell carcinoma treated by trimodality therapy.

Lymphopenia and Radiation Dose to Circulating Lymphocytes With Neoadjuvant Chemoradiation in Esophageal Squamous Cell Carcinoma.

Immuno-oncology (IO) therapies have transformed the therapeutic landscape of non-small cell lung cancer (NSCLC) However, patient responses to IO are variable and influenced by a heterogeneous combination of health, immune, and tumor factors There is a pressing need to discover the distinct NSCLC subgroups that influence response We have developed a deep patient graph convolutional network, we call "DeePaN", to discover NSCLC complexity across data modalities impacting IO benefit DeePaN employs high-dimensional data derived from both real-world evidence (RWE)-based electronic health records (EHRs) and genomics across 1937 IO-treated NSCLC patients DeePaN demonstrated effectiveness to stratify patients into subgroups with significantly different (P-value of 22 × 10-11) overall median survival of 2035 months and 942 months post-IO therapy Significant differences in IO outcome were not seen from multiple non-graph-based unsupervised methods Furthermore, we demonstrate that patient stratification from DeePaN has the potential to augment the emerging IO biomarker of tumor mutation burden (TMB) Characterization of the subgroups discovered by DeePaN indicates potential to inform IO therapeutic insight, including the enrichment of mutated KRAS and high blood monocyte count in the IO beneficial and IO non-beneficial subgroups, respectively Our work has proven the concept that graph-based AI is feasible and can effectively integrate high-dimensional genomic and EHR data to meaningfully stratify cancer patients on distinct clinical outcomes, with potential to inform precision oncology

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DeePaN: deep patient graph convolutional network integrating clinico-genomic evidence to stratify lung cancers for immunotherapy.

The neutrophil-to-lymphocyte (ANC/ALC) ratio is associated with worse prognosis in patients with NSCLC on immunotherapies, but the role of ALC remains unclear. The previous radiation therapy causes lymphopenia, and given approaches of combining radiation with immunotherapies, it is critical to better understand the impact of peripheral lymphocytes. We evaluated retrospectively 22 patients with advanced NSCLC treated with nivolumab at Boston Medical Center from January 2014 to September 2016 and correlated the peripheral blood counts with the overall survival (OS) and overall time on treatment. We assessed the effect of the previous radiation on peripheral blood counts and clinical outcomes. Baseline ALC and ANC/ALC ratios are positively and negatively correlated, respectively, with the OS on nivolumab. The ALC and ALC/WBC ratios at 6 weeks on treatment are positively associated with the OS. Kaplan–Meier analysis at baseline and at 6 weeks showed significantly increased OS in the group of patients with the highest ALC. The previous radiation therapy was positively correlated with the ANC and negatively correlated with the ALC/WBC ratio at 8 weeks after the initiation of nivolumab. Our finding that ALC at baseline and at 6 weeks on treatment is positively correlated with the OS provides an easily obtained predictive marker. Our result that the previous radiation is associated with higher ANC and lower ALC during treatment supports that the combination of radiation therapy with immunotherapy should be carefully applied and potentially peripheral blood counts can be utilized to stratify patients for this approach.

S. Karanika

Papers

The absolute lymphocyte count can predict the overall survival of patients with non-small cell lung cancer on nivolumab: a clinical study