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

Introduction: 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). Methods: 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. Results: 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). Conclusion: 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.

Early toxicities of ultrahypofractionated stereotactic body radiotherapy for intermediate risk localized prostate cancer using cone-beam computed tomography and real-time three-dimensional transperineal ultrasound monitoring.

PURPOSE: Image-guided radiotherapy (IGRT) is central to the safe and effective delivery of ultrahypofractionated (UF) stereotactic body radiotherapy (SBRT) for localized prostate cancer. However, the optimal IGRT modality remains uncertain. We aim to study the safety of performing UF-SBRT using cone-beam computed tomography (CBCT) and real-time transperineal ultrasound (TPUS) monitoring. MATERIALS AND METHODS: We retrospectively review the medical records of 26 patients who had received UF-SBRT for intermediate risk localized prostate cancer in our institution from October 2018 to December 2020. All patients were treated with SBRT without fiducial marker and received 35-40 Gy to the clinical target volume in 5 fractions over 2-5 weeks. CBCT was used to correct for interfraction displacement while intrafraction displacement of the prostate gland was monitored using Elekta Clarity Autoscan TPUS with 4 mm isotropic warning level. All patients also received neoadjuvant and concurrent androgen deprivation therapy for a total of 6 months. The primary endpoints were incidence of acute toxicities and patient reported urinary toxicities in terms of the International Prostate Symptom Score: before (IPSS1), at the completion of (IPSS2), and at 3-6 months (IPSS3) after SBRT. RESULTS: All men were treated and followed up for at least 3 months after SBRT. Patients experienced transient worsening of their urinary symptoms at the end of SBRT but they usually recovered in 3-6 months afterwards. The median IPSS1, IPSS2, and IPSS3 were 12, 12.5, and 8, respectively. One patient developed grade 3 rectal bleeding which was related to underlying hemorrhoid. No other grade 3-4 acute toxicity was observed. CONCLUSION: It appears safe to deliver UF-SBRT without fiducial marker for prostate cancer patients using CBCT and non-invasive hybrid imaging modalities for positioning and tracking. Longer follow-up is necessary to monitor the treatment efficacy and long-term toxicities.

Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data.

We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5-69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47-2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52-1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79-0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients.

Lipiodol versus diaphragm in 4D-CBCT-guided stereotactic radiotherapy of hepatocellular carcinomas.

PURPOSE: The purpose of this work was to investigate the potential of lipiodol as a direct tumor surrogate alternative to the diaphragm surrogate on four-dimensional cone-beam computed tomography (4D-CBCT) image guidance for stereotactic radiotherapy of hepatocellular carcinomas. METHODS: A total of 29 hepatocellular carcinomas (HCC) patients treated by stereotactic radiotherapy following transarterial chemoembolization (TACE) with homogeneous or partial defective lipiodol retention were included. In all, 4-7 pretreatment 4D-CBCT scans were selected for each patient. For each scan, either lipiodol or the diaphragm was used for 4D registration. Resulting lipiodol/diaphragm motion ranges and position errors relative to the reconstructed midventilation images were analyzed to obtain the motion variations, and group mean (ΔM), systematic (Σ), and random (σ) errors of the treatment setup. RESULTS: Of the lipiodolized tumors, 55 % qualified for direct localization on the 4D-CBCT. Significant correlations of lipiodol and diaphragm positions were found in the left-right (LR), craniocaudal (CC), and anteroposterior (AP) directions. ΔM and σ obtained with lipiodol and diaphragm were similar, agreed to within 0.5 mm in the LR and AP, and 0.3 mm in the CC directions, and Σ differed by 1.4 (LR), 1.1 (CC), and 0.6 (AP) mm. Variations of diaphragm motion range > 5 mm were not observed with lipiodol and in one patient with diaphragm. The margin required for the tumor prediction error using the diaphragm surrogate was 6.7 (LR), 11.7 (CC), and 4.1 (AP) mm. CONCLUSION: Image-guidance combining lipiodol with 4D-CBCT enabled accurate localization of HCC and thus margin reduction. A major limitation was the degraded lipiodol contrast on 4D-CBCT.