Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Shiraishi, Yasuyuki; Fang, Penny; Cai, Xu; Song, Juhee; Krishnan, Sunil; Koay, Eugene J.; Mehran, Reza J.; Hofstetter, Wayne L.; Blum-Murphy, Mariela; Ajani, Jaffer A.; Komaki, Ritsuko; Minsky, Bruce D.; Mohan, Radhe; Hsu, Charles C.; Hobbs, Brian P.; Lin, Steven H.

doi:10.1016/j.radonc.2017.11.028

Cited by 122 publications

(123 citation statements)

References 20 publications

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“…Because of this consideration, a possibility exists that the observed HR of 3.42 underrepresents the full effect of PNI on RRL incidence. The observed correlation between PNI and RRL comports with the results of several other papers that showed that increased treatment volumes were associated with higher rates of RRL 11 , 13 , 14 , 15 , 17 , 18 (though there is no uniform agreement on this subject 16 ), and these results merit further investigation for PNI in prostate cancer.…”

Section: Discussionsupporting

confidence: 86%

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

Schad

Dutta

Muller

et al. 2019

Advances in Radiation Oncology

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Purpose Given the uncertainty with regard to the effectiveness of pelvic nodal irradiation (PNI) for prostate cancer, we aimed to determine whether patients with prostate cancer who are treated with PNI are at a higher risk of developing radiation-related lymphopenia (RRL). Methods and materials The electronic charts of 886 consecutive patients treated with radiation therapy for prostate cancer between 2006 and 2018 at our institution were retrospectively analyzed. Qualifying patients were those with total lymphocyte counts within 1 year before and 3 to 24 months after the start of radiation therapy. Lymphopenia was the primary outcome, and overall survival and biochemical progression-free survival were secondary outcomes. Results Thirty-six patients with and 95 patients without PNI qualified for inclusion. In the PNI cohort, 61.1% of patients developed RRL (median follow-up total lymphocyte count < 1000 cells/μL) versus 26.3% of non-PNI patients ( P < .001). On univariate analysis, initial prostate-specific antigen level, baseline lymphopenia, treatment modality, PNI status, increased planned target volume, and androgen deprivation therapy administration were all significant predictors of RRL ( P < .05). On multivariate analysis, PNI status was a significant predictor of RRL (hazard ratio [HR], 3.42; 95% confidence interval [CI], 1.22-9.61; P < .001), as were initial prostate-specific antigen values (HR, 1.05; 95% CI, 1.00-1.11; P = .006) and baseline lymphopenia (HR, 8.32; 95% CI, 2.19-31.6; P = .007). RRL was not predictive for biochemical progression-free survival, distant metastasis, or overall survival on multivariate analysis, but the number of events was likely insufficient for these analyses. Conclusions The higher risk of RRL among patients with PNI comports with other papers that show that increased treatment volumes are associated with higher rates of RRL. Mounting evidence for the adverse effects of RRL on clinical outcomes supports the significance of our findings and suggests that further studies are needed on RRL as a potential harm of PNI that may affect the interpretation of results from clinical trials of PNI.

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Section: Discussionsupporting

confidence: 86%

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

Schad

Dutta

Muller

et al. 2019

Advances in Radiation Oncology

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“…Although previous studies reported that preoperative NLR might predict severe postoperative complications for colorectal, head and neck, and gastric surgery (26,(42)(43)(44)(45)(46) , in the present study NLR and PLR were not related to postoperative complications in esophageal carcinoma. The role of eosinophils in solid tumors is unclear, and may favor an antitumor inflammatory response, depending on the surrounding stimuli (47)(48)(49)(50) .…”

Section: Discussioncontrasting

confidence: 84%

Lymphocyte Count and Platelet Volume Predicts Postoperative Complications in Esophagectomy for Cancer: A Cohort Study

Tustumi

Takeda

Brandão

et al. 2019

Arq. Gastroenterol.

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BACKGROUND: Biomarkers from routine complete blood count are known predictive factors of long-term outcomes in cancer patients. The value of these biomarkers in the setting of trimodal therapy for esophageal cancer in predicting early postoperative outcomes is not studied. OBJECTIVE: The present study evaluated the value of cellular blood components changes during neoadjuvant chemoradiotherapy followed by curative intent esophagectomy for cancer in predicting postoperative mortality and morbidity. METHODS: A cohort of 149 consecutive patients that underwent chemoradiotherapy using platinum- and taxane-based regimens followed by esophagectomy was analyzed. Cellular components of blood collected before neoadjuvant therapy (period A) and before surgery (period B) were assessed for postoperative mortality and complications. Univariate and multivariate Cox regression models were applied to evaluate the independent prognostic significance of blood count variables. RESULTS: Postoperative morbidity was present in 46% of the patients. On multiple regression analysis platelet volume (B) (OR: 1.53; 95% CI: 1.2-2.33) was an independent predictor of general complications. Severe postoperative surgical complications were present in 17% of the patients. On multiple regression analysis, lymphocyte decrease between B-A periods (OR: 0.992; 95% CI: 0.990-0.997) was related to higher risk for severe complications. Cervical anastomotic leakage was present in 25.6% of the patients. On univariate analysis eosinophil count in A and B periods was related to cervical anastomotic leakage. For this outcome, multivariate joint model could not identify independent risk variables of cellular components of blood. The 30-day mortality rate was 7.4%. On univariate analysis, platelet count in period B was associated to higher risk for mortality. The multivariate joint model could not accurately predict mortality due to the few number of patients in the mortality group. CONCLUSION: This is the first study to assess the relationship between peripheral blood count variables changes during neoadjuvant chemoradiotherapy using a platinum- and taxane-based regimen followed by curative intent esophagectomy for cancer in predicting postoperative complications. The platelet volume prior to surgery is related to postoperative complications and the lymphocyte count change prior to surgery predicts severe postoperative complications in the setting of trimodal therapy for esophageal cancer.

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“…proton therapy may be correlated to less severe lymphopenia compared with photon therapy. 16,25,26 We do not have lymphocyte data available for our patients, but changes in total WBC count, neutrophils, and hemoglobin were not different between proton therapy and IMRT in our series. Based on modeling series, even a low dose of radiation to a small portion of the circulation per fraction results in the entire circulation being radiated after 30 fractions.…”

Section: Discussionmentioning

confidence: 64%

“…15 Beyond pneumonitis, there has also been clinical data that proton therapy can decrease heart dose compared with IMRT, and decrease lymphopenia, both of which may be associated with improved outcomes. 13,16 To address some of these open questions, we present here our institutional experience in patients with locally advanced lung cancer being treated with curative intent radiation therapy. We present real-life dosimetry and clinical outcomes with the newer generation scanning beam proton therapy and photon IMRT/volumetric modulated arc therapy (VMAT).…”

Section: Introductionmentioning

confidence: 99%

Scanning Beam Proton Therapy versus Photon IMRT for Stage III Lung Cancer: Comparison of Dosimetry, Toxicity, and Outcomes

Zou

Bowen

Hecking³

et al. 2020

Advances in Radiation Oncology

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There are limited clinical data on scanning-beam proton therapy (SPT) in treating locally advanced lung cancer, as most published studies have used passive-scatter technology. There is increasing interest in whether the dosimetric advantages of SPT compared with photon therapy can translate into superior clinical outcomes. We present our experience of SPT and photon intensity modulated radiation therapy (IMRT) with clinical dosimetry and outcomes in patients with stage III lung cancer. Methods and Materials: Patients with stage III lung cancer treated at our center between 2013 and May 2018 were identified in compliance with our institutional review board (64 patients Z 34 SPT þ 30 IMRT). Most proton patients were treated with pencil beam scanning (28 of 34), and 6 of 34 were treated with uniform scanning. Fisher exact test, c 2 test, and Mann-Whitney test were used to compare groups. All tests were 2-sided. Results: Patient characteristics were similar between the IMRT and SPT patients, except for worse lung function in the IMRT group. Mean dose to lung, heart, and esophagus was lower in the SPT group, with most benefit in the low-dose region (lungs, 9.7 Gy vs 15.7 Gy for SPT vs IMRT, respectively [P Z .004]; heart, 7 Gy vs 14 Gy [P Z .001]; esophagus, 28.2 Gy vs 30.9 Gy [P Z .023]). Esophagitis and dermatitis grades were not different between the 2 groups. Grade 2þ pneumonitis was 21% in the SPT group and 40% in the IMRT group (P Z .107). Changes in blood counts were not different between the 2 groups. Overall survival and progression-free survival were not different between SPT and IMRT (median overall survival, 41.6 vs 30.7 months, respectively [P Z .52]; median progression-free survival, 19.5 vs 14.6 months [P Z .50]). Conclusions: We report our experience with SPT and IMRT in stage III lung cancer. Our cohort of patients treated with SPT had lower doses to normal organs (lungs, heart, esophagus) than our IMRT cohort. There was no statistically significant difference in toxicity rates or survival, although there may have been a trend toward lower rates of pneumonitis.

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Severe lymphopenia during neoadjuvant chemoradiation for esophageal cancer: A propensity matched analysis of the relative risk of proton versus photon-based radiation therapy

Cited by 122 publications

References 20 publications

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

Radiation-related Lymphopenia after Pelvic Nodal Irradiation for Prostate Cancer

Lymphocyte Count and Platelet Volume Predicts Postoperative Complications in Esophagectomy for Cancer: A Cohort Study

Scanning Beam Proton Therapy versus Photon IMRT for Stage III Lung Cancer: Comparison of Dosimetry, Toxicity, and Outcomes

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