Splenic irradiation contributes to grade ≥ 3 lymphopenia after adjuvant chemoradiation for stomach cancer

• Published in: Clinical and translational radiation oncology Vol. 36; pp. 83 - 90
• Main Authors: Lee, Shing Fung, Yip, Pui Lam, Wong, Aray, Ng, Francesca, Koh, Vicky, Wong, Lea Choung, Luk, Hollis, Ng, Chuk Kwan, Lee, Francis Ann Shing, Mamon, Harvey J.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.09.2022; Elsevier
• Subjects: Gastric cancer; Normal tissue toxicity; Original; Postoperative chemoradiotherapy; Spleen; Survival; Spleen; Normal tissue toxicity; Gastric cancer; Survival; Postoperative chemoradiotherapy
• ISSN: 2405-6308; 2405-6308
• DOI: 10.1016/j.ctro.2022.07.007

•Severe lymphopenia occurs commonly after adjuvant chemoradiation for gastric cancer.•High splenic radiation doses increase the chances of severe lymphopenia.•Severe lymphopenia predicts a poorer overall survival and higher risk of infections.•The spleen is not routinely considered an organ-at-risk with dosimetric constraint.•Applying dose constraints to the spleen might lower the risk of severe lymphopenia. Adjuvant chemoradiation therapy (CRT) in gastric cancer inevitably results in an unintentional spleen radiation dose. We aimed to determine the association between the spleen radiation dose and the observed severity of lymphopenia which may affect the clinical outcomes (survival time and infection risk). Patients who received adjuvant CRT for gastric cancer between January 2015 and December 2020 were analyzed. The splenic dose-volume histogram (DVH) parameters were reported as mean splenic dose (MSD) and percentage of splenic volume receiving at least × Gray (Gy). Peripheral blood counts were recorded pre- and post-CRT. The development of severe (Common Terminology Criteria for Adverse Events, version 5.0, grade ≥ 3) post-CRT lymphopenia (absolute lymphocyte count [ALC] < 0.5 K/μL) was assessed by multivariable logistic regression using patient and dosimetric factors. Overall survival (OS), recurrence-free survival (RFS), and cumulative incidence of infectious events were estimated and analyzed using the Cox model or competing risk analysis. Eighty-four patients with a median follow-up duration of 42 months were analyzed. Pre- and post-CRT median ALC values were 1.8 K/μL (0.9–3.1 K/μL) and 0.9 K/μL (0.0–4.9 K/μL), respectively (P < 0.001). MSD > 40 Gy (odds ratio [OR], 1.13; 95 % confidence interval [CI], 1.01–1.26; P = 0.041), sex (OR for male to female, 0.25; 95 % CI, 0.09–0.70; P = 0.008), and baseline absolute neutrophil count (OR per 1 unit increase, 1.61; 95 % CI, 1.02–2.58; P = 0.040) were associated with the development of severe post-CRT lymphopenia, which was a risk factor for poorer OS (hazard ratio [HR] = 2.47; 95 % CI, 1.24–4.92; P = 0.010) and RFS (HR = 2.27; 95 % CI, 1.16–4.46; P = 0.017). The cumulative incidence of infections was higher among severe post-CRT lymphopenia patients (2.53, 95 % CI, 1.03–6.23, P = 0.043). High splenic radiation doses increase the odds of severe post-CRT lymphopenia, an independent predictor of lower OS and higher risks of recurrence and infections in gastric cancer patients receiving adjuvant CRT. Therefore, optimizing the splenic DVH parameters may decrease the risk of severe post-CRT lymphopenia.