Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy

Li, Yaqi; Fan, Xiaolin; Qi, Yu; Zhai, Haoyang; Mo, Miao; Sun, Jun; Mi, Jing; Lu, Renquan; Mao, Jingfang; Chen, Jian; Ma, Ningyi; Yang, Weijun; Zhu, Ji; Jia, Guanghong; K, Wu

doi:10.1016/j.ijrobp.2022.12.030

Cited by 10 publications

(7 citation statements)

References 38 publications

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“…27 In LA-NSCLC specifically, retrospective studies have shown that in addition to proton therapy, larger PTV, higher thoracic vertebral body V5 Gy, aorta V5 Gy, and lung V5 Gy were found to be important predictors of severe lymphopenia in those undergoing definitive treatment. 5,28 Our results also demonstrated that larger GTV and higher nodal stage were associated with G3 lymphopenia, suggesting that larger irradiated volumes could lead to a higher degree of lymphocyte depletion. In contrast to our results, other studies also found that severe radiation-induced lymphopenia was associated with inferior survival outcomes.…”

Section: Discussionsupporting

confidence: 58%

“…For instance, secondary analysis of a phase 2 randomized trial showed that proton therapy was associated with a reduction in grade 4 lymphopenia for patients with esophageal cancer undergoing cCRT 27 . In LA‐NSCLC specifically, retrospective studies have shown that in addition to proton therapy, larger PTV, higher thoracic vertebral body V5 Gy, aorta V5 Gy, and lung V5 Gy were found to be important predictors of severe lymphopenia in those undergoing definitive treatment 5,28 . Our results also demonstrated that larger GTV and higher nodal stage were associated with G3 lymphopenia, suggesting that larger irradiated volumes could lead to a higher degree of lymphocyte depletion.…”

Section: Discussionsupporting

confidence: 56%

See 1 more Smart Citation

Acute hospitalizations after proton therapy versus intensity‐modulated radiotherapy for locally advanced non–small cell lung cancer in the durvalumab era

Iocolano,

Yegya‐Raman,

Friedes

et al. 2024

Cancer

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IntroductionIt was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non–small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity‐modulated radiotherapy (IMRT).MethodsPatients with locally advanced non–small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90‐day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan–Meier method was used for progression‐free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups.ResultsOf 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38–0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37–0.81; p = .003). There was no difference in other G3+ toxicities, progression‐free survival, or overall survival.ConclusionsPBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

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Section: Discussionsupporting

confidence: 58%

Section: Discussionsupporting

confidence: 56%

Acute hospitalizations after proton therapy versus intensity‐modulated radiotherapy for locally advanced non–small cell lung cancer in the durvalumab era

Iocolano,

Yegya‐Raman,

Friedes

et al. 2024

Cancer

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“…For example, Xu et al indicated that G4 lymphopenia during CCRT was associated with higher lung V 10 and heart V 10 and poorer survival 11 . Another recent study conducted by the Shanghai Proton and Heavy Ion Center showed that severe lymphopenia was associated with aortic V 5 and affected prognosis 28 . Recently, a study that included 110 ESCC receiving IMRT showed that radiation‐induced lymphopenia (RIL) was associated with cardiac and pulmonary dose parameters, and the results also demonstrated that RIL could predict survival and radiation pneumonia 29 .…”

Section: Discussionmentioning

confidence: 99%

“… 11 Another recent study conducted by the Shanghai Proton and Heavy Ion Center showed that severe lymphopenia was associated with aortic V 5 and affected prognosis. 28 Recently, a study that included 110 ESCC receiving IMRT showed that radiation‐induced lymphopenia (RIL) was associated with cardiac and pulmonary dose parameters, and the results also demonstrated that RIL could predict survival and radiation pneumonia. 29 A meta‐analysis also revealed that RIL was associated with dosimetric factors such as PTV, cardiac dose, and effective dose to immune cells (EDIC), and it was correlated with lower pCR rates, as well as poorer OS and progression‐free survival (PFS).…”

Section: Discussionmentioning

confidence: 99%

Pericardial irradiation dose may be strongly associated with grade 4 lymphopenia and affect prognosis in patients with locally advanced esophageal cancer receiving definitive concurrent chemoradiotherapy

Chen

Tian²,

Zhang

et al. 2023

Thoracic Cancer

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BackgroundThe immune system may influence prognosis, and lymphopenia is a frequent side effect of concurrent chemoradiotherapy (CCRT). Radical irradiation for locally advanced esophageal cancer (LA‐EC) exposes significant vascular and heart volumes. In this study, we hypothesized that lymphopenia is linked to cardiac and pericardial doses and affects patient prognosis.Methods and MaterialsWe identified 190 LA‐EC patients who received radical CCRT. Multivariate analysis (MVA) was performed to correlate clinical factors and dosimetric parameters with overall survival (OS). We collected lymphocyte‐related variables and ratios before and during CCRT. MVA was performed to correlate hematologic toxicity with OS. The relationship between dosimetric parameters and G4 lymphopenia was determined using logistic stepwise regression. Finally, a nomogram of G4 lymphopenia was developed and validated externally.ResultsMedian follow‐up time for all patients was 27.5 months. On MVA for OS, higher pericardial V30 (PV30) was linked to worse survival (HR: 1.013, 95% CI: 1.001–1.026, p = 0.039). The median OS stratified by PV30 > 55.3% and PV30 ≤ 55.3% was 24.0 months and 54.0 months, respectively (p = 0.004). G4 lymphopenia was shown to be linked with worse OS in the MVA of hematological toxicity with OS (HR: 2.042, 95% CI: 1.335–3.126, p = 0.001). Thirty of the 100 patients in the training set had G4 lymphopenia. Logistic stepwise regression was used to identify variables associated with G4 lymphopenia, and the final model consisted of stage‐IVA (p = 0.017), platelet‐to‐lymphocyte ratio during CCRT (p = 0.008), Heart V50 (p = 0.046), and PV30 (p = 0.048). Finally, a nomogram predicting G4 lymphocytopenia were constructed and externally validated. The ROC curve showed an AUC for internal validation of 0.775 and external validation of 0.843.ConclusionHigher doses of pericardial radiation might affect LA‐EC patients' prognosis by inducing G4 lymphopenia during CCRT. Further prospective studies are warranted to confirm these findings, especially in the era of immune‐checkpoint inhibitor treatment.

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“…Similarly, the NICE study enrolled patients with multisite lymph node metastatic LA-ESCC who were treated with neoadjuvant chemotherapy in combination with camrelizumab immunotherapy and reported a pCR rate of 45.4% ( 30 ). Exploratory analyses have highlighted the detrimental effects of excessive irradiation on the heart and large blood vessels, leading to damage to the lymphatic system, which ultimately affects patient survival ( 31 – 33 ). For the first time, our study recorded a significant association between higher cardio-pulmonary irradiation and G4 lymphopenia in the nCRT setting, and the ENI technique was more likely to lead to lymphopenia ( p =0.019).…”

Section: Discussionmentioning

confidence: 99%

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival

Chen,

Zhang,

Zhou

et al. 2023

Front. Oncol.

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PurposeTo compare the differences between involved-field irradiation (IFI) and elective nodal irradiation (ENI) in selecting the optimal target area for neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC).Materials and methodsWe retrospectively analyzed 267 patients with LA-ESCC, of whom 165 underwent ENI and 102 underwent IFI. Dosimetry, treatment-related complications, pathological responses, recurrence/metastasis patterns, and survival were compared between the two groups.ResultsThe median follow-up duration was 27.9 months. The R0 resection rates in the IFI and ENI groups were 95.1% and 92.7%, respectively (p=0.441), while the pathological complete response (pCR) rates were 42.2% and 34.5%, respectively (p=0.12). The ENI group received higher radiation doses to the heart (HV30:23.9% vs. 18%, p=0.033) and lungs (LV30:7.7% vs. 4.9%, p<0.001) than the IFI group. Consequently, the ENI group showed a higher incidence of grade 2 or higher radiation pneumonitis (30.3% vs. 17.6%, p=0.004) and pericardial effusion (26.7% vs. 11.8%, p=0.021) than the IFI group. Post-operation fistulas were observed in 3 (2.9%) and 17 cases (10.3%) in the IFI and ENI groups, respectively (p=0.026). In the multivariate analysis, smoking, positive lymph node involvement (pN+), and anastomotic fistula were independent predictors of overall survival (OS). The pN+ patients exhibited a greater propensity for recurrence compared to pN- patients, especially in the first year of follow-up (6.67% vs. 0.56%, p=0.003).ConclusionThe ENI group had a higher incidence of radiation-induced adverse events compared to the IFI group, likely due to the higher radiation doses to normal tissues. Considering the similar disease-free survival (DFS) and OS rates in the two groups, IFI may be suitable for nCRT in patients with LA-ESCC, although further prospective studies are warranted.

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Proton and Carbon Ion Radiation Therapy Decreased Severe Lymphopenia by Reducing Thoracic Vertebra and Aortic Doses in Non-Small Cell Lung Cancer Versus Intensity Modulated Radiation Therapy

Cited by 10 publications

References 38 publications

Acute hospitalizations after proton therapy versus intensity‐modulated radiotherapy for locally advanced non–small cell lung cancer in the durvalumab era

Acute hospitalizations after proton therapy versus intensity‐modulated radiotherapy for locally advanced non–small cell lung cancer in the durvalumab era

Pericardial irradiation dose may be strongly associated with grade 4 lymphopenia and affect prognosis in patients with locally advanced esophageal cancer receiving definitive concurrent chemoradiotherapy

Involved-field irradiation or elective-nodal irradiation in neoadjuvant chemo-radiotherapy for locally-advanced esophageal cancer: comprehensive analysis for dosimetry, treatment-related complications, impact on lymphocyte, patterns of failure and survival

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