Dataset Information

Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy.

ABSTRACT:

Purpose

We investigated the dynamics of lymphocyte depletion and recovery during and after definitive concurrent chemoradiotherapy (CCRT), dose to which structures is correlated to them, and how they affect the prognosis of stage III non-small cell lung cancer (NSCLC) patients undergoing maintenance immunotherapy.

Methods and materials

In this retrospective study, absolute lymphocyte counts (ALC) of 66 patients were obtained before, during, and after CCRT. Persistent lymphopenia was defined as ALC < 500/μL at 3 months after CCRT. The impact of regional dose on lymphocyte depletion and recovery was investigated using voxel-based analysis (VBA).

Results

Most patients (n = 65) experienced lymphopenia during CCRT: 39 patients (59.0%) had grade (G) 3+ lymphopenia. Fifty-nine patients (89.3%) recovered from treatment-related lymphopenia at 3 months after CCRT, whereas 7 (10.6%) showed persistent lymphopenia. Patient characteristics associated with persistent lymphopenia were older age and ALC before and during treatment. In multivariable Cox regression analysis, recovery from lymphopenia was identified as a significant prognostic factor for Progression Free Survival (HR 0.35, 95% CI 0.13-0.93, p = 0.034) and Overall Survival (HR 0.24, 95% CI 0.08-0.68, p = 0.007). Voxel-based analysis showed strong correlation of dose to the upper mediastinum with lymphopenia at the end of CCRT, but not at 3 months after CCRT.

Conclusion

Recovery from lymphopenia is strongly correlated to improved survival of patients undergoing CCRT and adjuvant immunotherapy, and is correlated to lymphocyte counts pre- and post-CCRT. VBA reveals high correlation of dose to large vessels to lymphopenia at the end of CCRT. Therefore, efforts should be made not only for preventing lymphocyte depletion during CCRT but also for helping lymphocyte recovery after CCRT.

SUBMITTER: Cho Y

PROVIDER: S-EPMC9036741 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy.

Cho Yeona Y Kim Yejin Y Chamseddine Ibrahim I Lee Won Hee WH Kim Hye Ryun HR Lee Ik Jae IJ Hong Min Hee MH Cho Byung Chul BC Lee Chang Geol CG Cho Seungryong S Kim Jin Sung JS Yoon Hong In HI Grassberger Clemens C

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 20220113

<h4>Purpose</h4>We investigated the dynamics of lymphocyte depletion and recovery during and after definitive concurrent chemoradiotherapy (CCRT), dose to which structures is correlated to them, and how they affect the prognosis of stage III non-small cell lung cancer (NSCLC) patients undergoing maintenance immunotherapy.<h4>Methods and materials</h4>In this retrospective study, absolute lymphocyte counts (ALC) of 66 patients were obtained before, during, and after CCRT. Persistent lymphopenia w ...[more]

PMID: 35033601

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Project description:PurposeRadiation therapy (RT)-induced lymphopenia (RIL) is linked with inferior survival in esophageal and pancreatic cancers. Previous work has demonstrated a correlation between spleen dose and RIL risk. The present study correlates spleen dose-volume parameters with fractional lymphocyte loss rate (FLL) and total percent change in absolute lymphocyte count (%ΔALC) and suggests spleen dose constraints to reduce RIL risk.Methods and materialsThis registry-based study included 140 patients who underwent RT for pancreatic (n = 67), gastroesophageal (n = 61), or biliary tract (n = 12) adenocarcinoma. Patient-specific parameters of lymphocyte loss kinetics, including FLL and %ΔALC, were calculated based on serial ALCs obtained during RT. Spearman's rho was used to correlate spleen dose-volume parameters with %ΔALC, end-treatment ALC, and FLL. Multivariable logistic regression was used to identify predictors of ≥grade 3 and grade 4 RIL.ResultsSpleen dose-volume parameters, including mean spleen dose (MSD), all correlated with %ΔALC, end-treatment ALC, and FLL. Controlling for baseline ALC and planning target volume (PTV), an increase in any spleen dose-volume parameter increased the odds of developing ≥grade 3 lymphopenia. Each 1-Gy increase in MSD increased the odds of ≥grade 3 RIL by 18.6%, and each 100-cm3 increase in PTV increased the odds of ≥grade 3 lymphopenia by 20%. Patients with baseline ALC < 1500 cells/μL had a high risk of ≥grade 3 RIL regardless of MSD or PTV. FLL was an equally good predictor of ≥grade 3 lymphopenia as any spleen dose-volume parameter.ConclusionsIn patients undergoing RT for upper abdominal malignancies, higher spleen dose is associated with higher per-fraction lymphocyte loss rates, higher total %ΔALC, and increased odds of severe lymphopenia. Spleen dose constraints should be individualized based on baseline ALC and PTV size to minimize RIL risk, although our findings require validation in larger, ideally prospective data sets.

Project description:ObjectivesTo evaluate the efficacy and the incidence of symptomatic radiation pneumonitis (RP) of the adaptive radiation strategy with V20 limitation in stage III non-small cell lung cancer (NSCLC) patients receiving concurrent immunotherapy and radiotherapy Materials and Methods: We retrospectively reviewed stage III NSCLC patients received thoracic radiation with or without immunotherapy from January 2015 to September 2024 in the Third Xiangya Hospital. The overall survival (OS), progression free survival (PFS), objective response rate (ORR), and the incidence of symptomatic RP were compared among patients stratified by the sequential of immunotherapy and radiotherapy.Results45 patients received concurrent immunotherapy and radiotherapy with application of the adaptive radiation strategy (the CIR group). 32 patients received simultaneous integrated boost intensity-modulated radiotherapy (SIB-IMRT), 26 patients received 2 to 4 cycles neoadjuvant immuno-chemotherapy before the concurrent immunotherapy and radiotherapy, 7 patients received thoracic radiotherapy with a prescribed dosage of 50 Gy, and 10 patients received radiotherapy with CTV omission. 86.67 % (39/45) patients had a V20 ≤ 20 %. The ORR was 86.67 %. The median PFS of these patients was significantly longer than those received concurrent chemo-radiotherapy followed by immunotherapy (the PACIFIC paradigm, HR, 2.40; 95 % CI, 1.15 to 5.02; log-rank p = 0.013; median, 28.6 vs. 16.1 months p = 0.013). The median OS was not reached. 13.3 % patients in the CIR group experienced grade ≥ 2 RP and the incidence was significantly lower than that of patients received radiotherapy without immunotherapy or concurrent chemo-radiotherapy with immunotherapy consolidation.ConclusionsThe application of adaptive radiotherapy strategies with V20 limitation demonstrated robust antitumor activity and reduced pulmonary toxicity in stage III NSCLC patients receiving concurrent ICIs treatment and thoracic radiation. This treatment modality deserves further validation as a promising therapy in patients with treatment-naive, unresectable, stage III NSCLC.

Project description:BackgroundDurvalumab as maintenance treatment after platinum-based concurrent chemoradiotherapy (cCRT) has become the standard of care in inoperable stage III non-small cell lung cancer (NSCLC). In this nationwide survey, we solicited members of the German Radiation Oncology Society to review the current distribution and clinical settings of durvalumab treatment after cCRT, observed side effects and summarize follow-up management.MethodsWe surveyed radiation oncology institutions in Germany via an anonymous online questionnaire sent by e-mail to all members of the German Radiation Oncology Society which agreed their willingness to participate.ResultsWe received a total of 255 responses (response rate: 18%). Of which 203 (80%) were completed and returned and thus eligible for further evaluation. The respondents work in 87 different cities and 44% in a private medical practice, 29% in university and 22% in a general hospital. Durvalumab was implemented in clinical routine by 70% of respondents. Major reasons for failed implementation in clinical practice reported by the respondents were patient's ineligibility (42%), lack of required PD-L1 status (25%), decision of medical oncologists (7%) or absence of updated German guidelines (7%). Thirty-six percent of all respondents report low (≤30%) PD-L1 testing before cCRT based on IHC assay. No respondent had applied durvalumab in less than 14 days after the completion of CRT. Severe side effects requiring hospital admission in more than 10% of all patients were reported by 12% of all respondents.ConclusionsDurvalumab maintenance is already implemented in the radiation oncology community and administered by the absolute majority of respondents. Low testing rates of PD-L1 at initial diagnosis were observed and should be considered a major barrier to universal adoption and integration in the clinical work-flow in countries with durvalumab approval restricted to PD-L1 positive patients. No respondent applies durvalumab in less than 14 days after cCRT.

Dataset Information

Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy.

Purpose

Methods and materials

Results

Conclusion

Publications

Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy.

Similar Datasets

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