Impact of Treatment-Related Lymphopenia on Immunotherapy for Advanced Non-Small Cell Lung Cancer

Cho, Yeona; Park, Sangjoon; Byun, Hwa Kyung; Lee, Chang Geol; Cho, Jaeho; Hong, Min Hee; Kim, Hye Ryun; Cho, Byoung Chul; Kim, Sinae; Park, Ju‐Young; Yoon, Hong In

doi:10.1016/j.ijrobp.2019.08.047

Cited by 109 publications

(97 citation statements)

References 28 publications

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“…11 A recent study clearly demonstrates that lymphopenia is indicative of poor prognosis in non-small cell lung cancer (NSCLC) patients receiving immunotherapy. 12,13 Nonetheless, to date, immunotherapy is usually administered in advanced stage or metastatic lung carcinoma when the lymphocyte count is already expected to be low. 14 Furthermore, based on a recent study, platelets are also greatly involved in immune regulation, tumor cell cross-talk and tumor growth.…”

Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of complete blood count parameters in advanced‐stage lung cancer patients

et al. 2020

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Background Metastatic lung cancer is a debilitating disease, but with the advances in immunotherapy, therapeutic options have vastly increased. Numerous complete blood count parameters (CBC) have been described as easily accessible biomarkers that might predict response to immunotherapy. However, to date, no comprehensive study has been performed on the longitudinal changes of these parameters during cancer progression. Methods The clinicopathological variables and CBC parameters of 986 advanced stage lung cancer patients were retrospectively analyzed. Blood tests were performed as part of the routine checkup and the results were recorded at the time of the diagnosis of the primary tumor, the diagnosis of brain or bone metastases, and also during the last available follow‐up. Results In the experimental subcohort, 352 and 466 patients were diagnosed with brain and bone metastases, respectively. The control group consisted of 168 patients without clinically detectable or other distant organ metastases. In our longitudinal analyses, we found significantly decreasing absolute lymphocyte count (ALC: P < 0.001), and significantly increasing absolute neutrophil count (ANC: P < 0.001) levels in all patient subgroups, irrespective of histopathological type and metastatic site. Interestingly, patients with brain metastases had significantly descending‐ascending platelet count (PLT) trendlines ( P < 0.001), while the bone metastatic subgroup exhibited significantly ascending‐descending trendlines ( P = 0.043). Conclusions Significantly decreasing ALC, significantly increasing ANC and fluctuating PLT levels may be found in brain and bone metastatic lung cancer patients during disease progression. Our findings might contribute to improve personalized healthcare in this devastating malignancy. Key points Significant findings of the study Significantly decreasing ALC, and significantly increasing ANC levels can be found in advanced‐stage lung cancer patients during disease progression Patients with brain metastases have descending‐ascending PLT trendlines, while patients with bone metastases exhibit ascending‐descending trendlines during disease progression What this study adds The descending values for ALC, and the ascending mean values for PLT and ANC, might be suggestive of poor response to second‐ or third‐line immunotherapy in advanced‐stage lung cancer patients. The current study might help to improve patient selection and treatment strategies for brain and/or bone metastatic lung cancer patients.

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Section: Introductionmentioning

confidence: 99%

Longitudinal analysis of complete blood count parameters in advanced‐stage lung cancer patients

et al. 2020

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“…The mean lymphocyte count at two months was below 1000 cells/mm 3 , exceeding this count only at six months after radiotherapy. Cho et al 5 showed that patients with metastatic lung cancer treated with immunotherapy had an OS of 5.7 versus 12.1 months (P < 0.001) when lymphocyte counts were less than or greater than 1000 cells/mm 3 , respectively. The median PTV in our sample was 532 cc, including the primary tumor plus involved lymph nodes with CTV and ITV margins, which resulted in a large volume of irradiated blood.…”

Section: Discussionmentioning

confidence: 99%

“…3 Blockade of programmed death 1 (PD-1) and programmed death ligand 1 (PD-L1) has allowed increased local tumor control and survival in patients with lung cancer 4 but treatment success may be hindered if total and CD4 lymphocyte counts are reduced. 5 A sufficient lymphocyte count is necessary for PD-1/PD-L1 blockade to occur, via immunosuppression, and to allow an increase in immune activity. It has been shown that absolute lymphocyte count <500 cells/mL can compromise the action of drugs that block the PD-1/PD-L1 pathway in several tumor types.…”

Section: Introductionmentioning

confidence: 99%

Impacts of post‐radiotherapy lymphocyte count on progression‐free and overall survival in patients with stage III lung cancer

et al. 2020

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Background We evaluated the impact of thoracic radiation in patients with non‐small cell lung cancer (NSCLC), considering the depletion of total lymphocytes, use or not of chemotherapy, and radiation doses in healthy lung tissue. Methods Patients with stage III NSCLC, ECOG 0 to 2, receiving radiotherapy with or without chemotherapy were prospectively evaluated. All patients should be treated with three‐dimensional radiotherapy and received biologically effective doses (BED10α/β 10) of 48 to 80 Gy. Peripheral blood lymphocyte total counts were measured at the start of radiotherapy and at 2, 6 and 12 months after radiotherapy. Along with lymphocytes, PTV and doses of 5 Gy and 20 Gy in healthy lung tissue were also evaluated as potential factors influencing overall survival (OS) and progression‐free survival (PFS). Results A total of 46 patients were prospectively evaluated from April 2016 to August 2019, with a median follow‐up of 13 months (interquartile range, 1–39 months). The median of OS of all cohort was 22,8 months (IC 95% 17,6–28,1) and the median PFS was 19,5 months (IC 95%: 14,7–24,2). Most patients received concurrent or neoadjuvant chemotherapy (43; 93.4%). No patient received adjuvant immunotherapy. The lower the lymphocyte loss at 6 months after radiotherapy (every 100 lymphocytes/mcL), the greater the chance of PFS (HR, 0.44; 95%CI, 0.25–0.77; P = 0.004) and OS (HR, 0.83; 95%CI, 0.70–0.98; P = 0.025; P = 0.025). BED was a protective factor for both PFS (HR, 0.52; 95%CI 0.33–0.83; P = 0.0006) and OS (HR, 0.73; 95%CI 0.54–0.97; P = 0.029). Conclusions Our results suggest that lymphocyte depletion after radiotherapy reduces tumor control and survival in patients with stage III lung cancer. Radiation doses equal or higher than 60 Gy (BED 10 72 Gy) improve PFS and OS, but they negatively affect lymphocyte counts for months, which reduces survival and the potential of immunotherapy. Key points Significant findings of the study Thoracic irradiation for locally advanced lung cancer depletes T lymphocytes for months. Patients whose lymphocyte loss is lower have better overall survival and progression‐free survival. What this study adds It is necessary to protect the lymphocyte population, as well as other organs at risk. New forms of irradiation for large fields are needed. Furthermore, could immunotherapy before chemo‐radiotherapy, with a greater number of lymphocytes, bring an even better result?

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“…Conversely, lymphocytes are known to play a fundamental role in cell-mediated immune response against cancer. Lymphopenia, which re ects the decreased immune surveiilance against cancer, has been reportedly to be associated with poor survival in various solid tumors [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma

Hong

Cho²,

Yoon

2020

Preprint

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Background Regorafenib has shown promising results as a second-line therapy for patients with hepatocellular carcinoma (HCC) who progressed on sorafenib. Although several data regarding the efficacy of sequential therapy with sorafenib and that of regorafenib in real-life, specific inflammation markers for predicting the prognosis have not been studied. This study aimed to investigate prognostic value of systemic inflammatory markers in patients with HCC who received sorafenib-regorafenib sequential therapy. Methods We retrospectively analyzed medical data of patients who received regorafenib for the treatment of HCC after sorafenib failure. Progression free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier survival curves. Univariate and multivariate analyses were performed to analyze the factors associated with survival. Results A total of 58 patients who received at least one dose of regroafenib and fulfilled the eligibility criteria, good performance status (Eastern Cooperative Oncology Group [ECOG] 0–1) and preserved liver function (Child-Pugh-A), were included in the analysis. The median PFS was 3 months (95% confidence interval [CI] = 0.981–5.019) and the median OS was 8 months (95% CI = 5.761–10.239). Elevated systemic immune-inflammation index (SII ≥ 340) was independently associated with poor OS. In multivariate analysis, the SII (hazard ratio [HR] = 2.211, 95% CI = 1.089–4.489, P = 0.028) and alpha-fetoprotein (AFP) (HR = 2.750, 95% CI = 1.259–6.010, P = 0.011) were independent predictors of OS. Conclusion Elevated SII is associated with poor OS in patients with HCC who received sequential therapy with sorafenib and regorafenib. In addition, when selecting a treatment strategy, the SII can be used in combination with the AFP level as a promising prognostic tool for HCC.

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Impact of Treatment-Related Lymphopenia on Immunotherapy for Advanced Non-Small Cell Lung Cancer

Cited by 109 publications

References 28 publications

Longitudinal analysis of complete blood count parameters in advanced‐stage lung cancer patients

Longitudinal analysis of complete blood count parameters in advanced‐stage lung cancer patients

Impacts of post‐radiotherapy lymphocyte count on progression‐free and overall survival in patients with stage III lung cancer

Systemic immune-inflammation index predicts prognosis of sequential therapy with sorafenib and regorafenib in hepatocellular carcinoma

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