Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab

Ikoma, Tatsuki; Shimokawa, Mototsugu; Matsumoto, Toshihiko; Boku, Shogen; Yasuda, Takenori; Shibata, Nobuhiro; Kurioka, Yusuke; Takatani, Masahiro; Nobuhisa, Tetsuji; Namikawa, Tsutomu; Kitagawa, Hiroyuki; Hanazaki, Kazuhiro; Doi, Kouki; Shimada, Takanobu; Tsumura, Takehiko; Marusawa, Hiroyuki; Kanaya, Seichiro; Morita, Shuko; Inokuma, Tetsurou; Nagai, Hiroki; Yasui, Hisateru; Satake, Hironaga

doi:10.1007/s00262-022-03265-7

Cited by 12 publications

(14 citation statements)

References 33 publications

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“…We found that the CAR is a promising indicator of nutritional status. Cancer induces inflammatory cytokines, such as interleukin (IL)-6 and tumor necrosis factor (TNF)-α, and causes LBW [ 6 , 9 , 13 ]. Therefore, nutritional indicators reflecting these cytokines may indicate cancer cachexia more sensitively.…”

Section: Discussionmentioning

confidence: 99%

“…We collected data on body weight changes at three time points: onset of first-line treatment, onset of pretreatment with nivolumab, and onset of nivolumab treatment. Additionally, nutritional status was investigated by evaluating the C-reactive protein/albumin ratio (CAR) [ 9 , 10 , 11 ] based on blood tests at the three time points. We also investigated the changes in CAR during prior nivolumab treatments.…”

Section: Methodsmentioning

confidence: 99%

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Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy

Ikoma

Matsumoto

Kurioka

et al. 2022

JCM

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Nivolumab improves overall survival (OS) in patients with advanced gastric cancer (AGC) refractory to at least two previous chemotherapy regimens. We investigated whether changes in body weight and nutrition from first-line chemotherapy to nivolumab affected its efficacy. The correlation between weight change and nutritional status up to the start of nivolumab treatment and OS and progression-free survival (PFS) after starting nivolumab treatment was determined. Nutritional status was examined using the C-reactive protein/albumin ratio (CAR). A loss in body weight (LBW) from the onset of the first treatment of <4.5% led to OS prolongation and improved PFS outcomes. The median OS values in the LBW < 4.5% and ≥4.5% groups were 11.4 and 3.6 months, respectively. Similarly, changes in CAR from first-line chemotherapy (ΔCAR) affected OS; the ΔCAR < 0.01 group had a better prognosis than the ΔCAR ≥ 0.01 group. The median OS values in the ΔCAR < 0.01 and ≥0.01 groups were 9.4 and 4.5 months, respectively. The median OS in the group with LBW < 4.5% and ΔCAR < 0.01 was 12.9 months. LBW and deterioration of nutritional status following first-line chemotherapy are poor prognostic factors in AGC patients who received nivolumab as third- or later-line therapy. Early intervention to maintain body weight and nutritional status may improve the efficacy of immune checkpoint inhibitors.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy

Ikoma

Matsumoto

Kurioka

et al. 2022

JCM

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“…22,49,50 The increasing stature of immunotherapies has led to the identification and validation of a wide range of therapeutic biomarkers related to the prediction of tumor efficacy, including microsatellite viability and mismatch response, PD-L1 CPS scores, MHC-II molecules, CD73, CD8, and neoantigen. 22,51,52 In the present study, however, the association of these biomarkers with ICI treatment has yet to be fully demonstrated and requires further investigation and exploration in the future.…”

Section: Therapeutic Advances Inmentioning

confidence: 80%

Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma

et al. 2023

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Objective: To investigate the efficacy and safety differences between the cisplatin + paclitaxel (TP) and cisplatin + fluorouracil (PF) regimens in combination with or without immune checkpoint inhibitors (ICIs) in advanced esophageal squamous cell carcinoma (ESCC) first-line treatment and prognostic factors. Methods: We selected the medical records of patients with late stage ESCC admitted to the hospital between 2019 and 2021. Based on the first-line treatment regimen, control groups were divided into chemotherapy plus ICIs ( n = 243) and non-ICIs ( n = 171), 119 (49%) in the TP + ICIs group, 124 (51%) in the PF + ICIs group, 83 (48.5%) in the TP group, and 88 (51.5%) in the PF group in the control group. We analyzed and compared factors related to efficacy, safety, or response to toxicity and prognosis across four subgroups. Results: The overall objective response rate (ORR) and disease control rate (DCR) of the TP plus ICIs group were 42.1% (50/119) and 97.5% (116/119), respectively, which were 6.6% and 7.2% higher than those of the PF plus ICIs group. Patients in the TP combined with ICIs group had higher overall survival (OS) and progression-free survival (PFS) than those in the PF combined with ICIs group [hazard ratio (HR) = 1.702, 95% confidence interval (CI): 0.767–1.499, p = 0.0167 and HR = 1.158, 95% CI: 0.828–1.619, p = 0.0055] ORR and DCR were 15.7% (13/83) and 85.5% (71/83) in the TP chemotherapy alone group, significantly higher than the PF group [13.6% (12/88) and 72.2% (64/88)] ( p < 0.05), OS and PFS were also better in patients treated with TP regimen chemotherapy than PF (HR = 1.173, 95% CI: 0.748–1.839, p = 0.0014 and HR = 0.1.245, 95% CI: 0.711–2.183, p = 0.0061). Furthermore, following the combination of TP and PF diets with ICIs, the OS of the patients was higher than that of the group treated with chemotherapy alone (HR = 0.526, 95% CI: 0.348–0.796, p = 0.0023 and HR = 0.781, 95% CI: 0.0.491–1.244, p < 0.001). Regression analysis showed that the neutrophil-to-lymphocyte ratio (NLR), the control nuclear status score (CONUT), and the systematic immune inflammation index (SII) were independent prognostic factors for the efficacy of immunotherapy ( p < 0.05). The overall incidence of treatment-associated adverse events (TRAEs) was 79.4% (193/243) and 60.8% (104/171) in the experimental and control groups, respectively, and there was no statistically significant difference in TRAEs between TP + ICIs (80.6%) and PF + ICIs (78.2%) (61.4%) and PF groups (60.2%) ( p > 0.05). Overall, 21.0% (51/243) of patients in the experimental group experienced immune-related adverse events (irAEs), and all of these adverse effects were tolerated or remitted following drug treatment without affecting follow-up. Conclusion: The TP regimen was associated with better PFS and OS with or without ICIs. Furthermore, high CONUT scores, high NLR ratios, and high SII were found to be associated with poor prognosis in combination immunotherapy.

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“…We investigated three factors: body mass index (BMI), neutrophil/lymphocyte ratio (NLR), and C-reactive protein (CRP)/albumin (Alb) ratio (CAR) [ 17 ]. These factors were obtained from the results of the physical examination and blood test on the date of the first IO therapy initiation.…”

Section: Methodsmentioning

confidence: 99%

Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study

Ikoma,

Matsumoto,

Boku

et al. 2024

Cancer Immunol Immunother

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Background Immuno-oncology (IO) drugs are essential for treating various cancer types; however, safety concerns persist in older patients. Although the incidence of immune-related adverse events (irAEs) is similar among age groups, higher rates of hospitalization or discontinuation of IO therapy have been reported in older patients. Limited research exists on IO drug safety and risk factors in older adults. Our investigation aimed to assess the incidence of irAEs and identify the potential risk factors associated with their development. Methods This retrospective analysis reviewed the clinical data extracted from the medical records of patients aged > 80 years who underwent IO treatment at our institution. Univariate and multivariate analyses were performed to assess the incidence of irAEs. Results Our study included 181 patients (median age: 82 years, range: 80–94), mostly men (73%), with a performance status of 0–1 in 87% of the cases; 64% received IO monotherapy. irAEs occurred in 35% of patients, contributing to IO therapy discontinuation in 19%. Our analysis highlighted increased body mass index, eosinophil counts, and albumin levels in patients with irAEs. Eosinophil count emerged as a significant risk factor for any grade irAEs, particularly Grade 3 or higher, with a cutoff of 118 (/μL). The group with eosinophil counts > 118 had a higher frequency of irAEs, and Grade 3 or higher events than the group with counts ≤ 118. Conclusion IO therapy is a safe treatment option for patients > 80 years old. Furthermore, patients with elevated eosinophil counts at treatment initiation should be cautiously managed.

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Inflammatory prognostic factors in advanced or recurrent esophageal squamous cell carcinoma treated with nivolumab

Cited by 12 publications

References 33 publications

Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy

Improvement of Body Weight and Nutritional Status in Gastric Cancer Patients Enhances the Benefit of Nivolumab Therapy

Retrospective study of the combination of TP and PF regimens with or without immune checkpoint inhibitors for the first-line treatment of locally advanced or advanced esophageal squamous cell carcinoma

Safety of immune checkpoint inhibitors in patients aged over 80 years: a retrospective cohort study

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