Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

Chadha, Awalpreet S.; Guan, Lan; Chen, Hsiang Chun; Das, Prajnan; Minsky, Bruce D.; Mahmood, Usama; Delclos, Marc E.; Suh, Yelin; Sawakuchi, Gabriel O.; Beddar, Sam; Katz, Matthew H.; Fleming, Jason B.; Javle, Milind; Varadhachary, Gauri R.; Wolff, Robert A.; Crane, Christopher H.; Wang, Xuemei; Thames, Howard D.; Krishnan, Sunil

doi:10.1016/j.ijrobp.2016.10.046

Cited by 90 publications

(80 citation statements)

References 39 publications

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“…Irradiation of both primary lymphoid organs, including functional bone marrow and thymus, and secondary lymphoid organs such as spleen may lead to damage and decrease in lymphocytes following treatment [23][24][25]. Moreover, Yovino et al estimated that 99% of circulating blood receives at least 0.5 Gy after 60 Gy (in 2 Gy fractions) of delivered RT dose in glioma patients [26].…”

Section: Discussionmentioning

confidence: 99%

Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy

Abravan

Eide

Helland

et al. 2020

Clinical and Translational Radiation Oncology

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Background: Lymphopenia during radiotherapy (RT) may have an adverse effect on treatment outcome. The aim of this study is to investigate associations between lymphopenia and RT parameters in patients with advanced lung cancer. Moreover, to investigate the prognostic role of lymphopenia, blood protein levels, and treatment and patient-related factors. Material and Methods: Sixty-two advanced stage non-small cell lung cancer (NSCLC) patients were retrospectively analyzed. Blood counts were available prior to, during, and after RT (3Gyx10). For each patient, a thoracic volume of interest (VOI)-including thoracic soft tissue and trabecular bone-was obtained by applying a CT window of À500 to 1200 HU in the planning CT. Dose parameters from thoracic VOI and other regions including lungs and vertebrae were calculated. Association between risk of lymphopenia ! G3 (lymphocytes at nadir according to CTCAE v4.0) and therapeutic parameters was investigated using Logistic regression. Relationships between overall survival (OS) and RT dose parameters, baseline blood counts and protein levels, and clinical factors were evaluated using Log-rank and Cox models. Result: Mean thoracic RT dose (odds ratio [OR] 1.67; p = 0.04), baseline lymphocytes (OR 0.65; p = 0.01), and corticosteroids use (OR 6.07; p = 0.02) were significantly associated with increased risk of lymphopenia ! G3 in multivariable analysis. Worse OS was associated with high mean thoracic RT dose, high CRP/ Albumin, large tumor volume and corticosteroids use (p < 0.05, univariate analysis), but not with lymphopenia ! G3. CRP/Albumin ratio > 0.12 (hazard ratio [HR] 2.28, p = 0.03) and corticosteroid use (HR 2.52, p = 0.01) were independently associated with worse OS. Conclusion: High thoracic RT dose gave a higher risk of lymphopenia ! G3; hence limiting dose volume to the thorax may be valuable in preventing severe lymphopenia for patients receiving palliative fractionated RT. Still, lymphopenia ! G3 was not associated with worse OS. however, high baseline CRP/ Albumin was associated with poorer OS and may carry important information as a prognostic factor of OS in advanced NSCLC receiving palliative RT.

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Section: Discussionmentioning

confidence: 99%

Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy

Abravan

Eide

Helland

et al. 2020

Clinical and Translational Radiation Oncology

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“…However, splenic irradiation presents a unique challenge as it can lead to immunosuppression from functional hyposplenia and lymphopenia, potentially reducing the body's anti-tumor immune response and increasing the risk for infection. Higher mean spleen radiation dose has been associated with post-irradiation lymphopenia, [38][39][40] and SBRT-induced severe lymphopenia with an absolute lymphocyte count of less than 0.5 K/UL in lung cancer patients has been correlated with worse overall survival. 41 In addition, splenic irradiation with 40 Gy has been shown to cause splenic atrophy and functional hyposplenia, placing patients at risk for developing pneumococcal sepsis.…”

Section: Discussionmentioning

confidence: 99%

Stereotactic Body Radiation Therapy to a Splenic Metastasis in Oligoprogressive Non-small Cell Lung Cancer

Kim

Lee

et al. 2020

Advances in Radiation Oncology

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“…Our results suggesting the predictive value of spleen dosevolume parameters, are consistent with several studies. A study of 177 patients with locally advanced pancreatic cancer who received CRT demonstrated that higher splenic doses increased the risk of the development of severe post-CRT lymphopenia (10). A study of 59 patients with hepatocellular carcinoma demonstrated that higher spleen irradiation doses correlated significantly with lower minimum ALC during RT for hepatocellular carcinoma (21).…”

Section: Discussionmentioning

confidence: 99%

Spleen Dose–Volume Parameters as a Predictor of Treatment-related Lymphopenia During Definitive Chemoradiotherapy for Esophageal Cancer

Saitô

Toya

Yoshida

et al. 2018

In Vivo

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Aim: Our study sought to identify dosimetric predictors of treatment-related lymphopenia during chemoradiotherapy for esophageal cancer. Materials and Methods: Patients with esophageal cancer who had received definitive chemoradiotherapy at our Institution were retrospectively assessed. The absolute volume of the spleen, body, and bone marrow that had received 5, 10, 20, and 30 Gy and the mean splenic dose were recorded. Results: Multivariate linear regression analysis revealed that docetaxel use and spleen dose-volume parameters (V5, V10, V20, V30, and mean splenic dose) were significant independent factors negatively influencing the absolute lymphocyte count at nadir. An increase of 1 Gy in mean splenic dose predicted a 2.9% decrease in nadir absolute lymphocyte count. Univariable logistic regression analysis showed that the mean splenic dose was a significant predictor of grade 4 lymphopenia. None of the body or bone marrow dose-volume parameters significantly predicted lymphopenia. Conclusion: Higher spleen dose-volume parameters were associated with severe lymphopenia during chemoradiotherapy. The important role of lymphocytes in the immune response to cancer is evidenced by reports that show better survival of patients with lung, colorectal, and breast cancer who have lymphocyte infiltration in the tumor tissue (1-3). Recent studies demonstrated that treatment-related lymphopenia was associated with poor outcome in patients undergoing definitive chemoradiotherapy (CRT) for esophageal, pancreatic, lung, cervical, and nasopharyngeal cancer (4-8). Lymphocytes are highly radiosensitive, and exposure to low doses of radiation can lead to a decrease in the number of peripheral blood lymphocytes (9). Radiation-related lymphopenia can thus affect the immune system and the treatment outcome. Previous studies have suggested that radiation-related lymphopenia is associated with the irradiation of lymphoid tissue including the spleen (10) and bone marrow (11), or the irradiation of peripheral blood lymphocytes (12,13). However, in CRT for esophageal cancer, mechanisms of treatment-related lymphopenia have not been clarified. Therefore, focusing on dose-volume parameters, we sought to identify predictors of lymphopenia during CRT for esophageal cancer. Materials and Methods Patients. This retrospective study was approved by the Institutional Review Board of our hospital (approval number, 1533). Patient informed consent was waived due to the retrospective nature of the study. The study was carried out according to the Declaration of Helsinki. Our inclusion criteria were as follows: Patients who completed definitive CRT for esophageal cancer between January 2011 and August 2015 and whose chemotherapy regimen included cisplatin. The exclusion criteria were: Previous radiotherapy (RT); chemotherapy performed before CRT; and CRT performed as preoperative treatment. Laboratory data. The study endpoints were as follows: (i) the absolute lymphocyte count (ALC) at nadir, defined as the lowest value recorded during CRT; and (ii) ...

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Does Unintentional Splenic Radiation Predict Outcomes After Pancreatic Cancer Radiation Therapy?

Cited by 90 publications

References 39 publications

Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy

Radiotherapy-related lymphopenia in patients with advanced non-small cell lung cancer receiving palliative radiotherapy

Stereotactic Body Radiation Therapy to a Splenic Metastasis in Oligoprogressive Non-small Cell Lung Cancer

Spleen Dose–Volume Parameters as a Predictor of Treatment-related Lymphopenia During Definitive Chemoradiotherapy for Esophageal Cancer

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