Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer

Background Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. Methods Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. Results Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38–18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09–9.19, respectively). Conclusions Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.

MRI-Based Random Survival Forest Model Improves the Prediction of Progression-Free Survival to Induction Chemotherapy plus Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma

BackgroundThe present study aimed to explore the application value of random survival forest (RSF) model and Cox model in predicting the progression-free survival (PFS) among patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) after induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT).MethodsEligible LANPC patients underwent magnetic resonance imaging (MRI) scan before treatment were subjected to radiomics feature extraction. Radiomics and clinical features of patients in the training cohort were subjected to RSF analysis to predict PFS and were tested in the testing cohort. The performance of an RSF model with clinical and radiologic predictors was assessed with the area under the receiver operating characteristic (ROC) curve (AUC) and Delong test and compared with Cox models based on clinical and radiologic parameters. Further, the Kaplan-Meier method was used for risk stratification of patients.ResultsA total of 294 LANPC patients (206 in the training cohort; 88 in the testing cohort) were enrolled and underwent magnetic resonance imaging (MRI) scans before treatment. The AUC value of the clinical Cox model, radiomics Cox model, clinical + radiomics Cox model, and clinical + radiomics RSF model in predicting 3- and 5-year PFS for LANPC patients was [0.545 vs 0.648 vs 0.648 vs 0.899 (training cohort), and 0.566 vs 0.736 vs 0.73 vs 0.861 (testing cohort); 0.556 vs 0.604 vs 0.611 vs 0.897 (training cohort), and 0.591 vs 0.661 vs 0.676 vs 0.847 (testing cohort), respectively]. Delong test showed that the RSF model and the other three Cox models were statistically significant, and the RSF model markedly improved prediction performance (P<0.001). Additionally, the PFS of the high-risk group was lower than that of the low-risk group in the RSF model (P<0.001), while comparable in the Cox model (P>0.05).ConclusionThe RSF model may be a potential tool for prognostic prediction and risk stratification of LANPC patients.

Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial

Objective To investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC). Methods We retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up. Results The leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P<0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P<0.05). The absolute neutrophil count was 4.17±0.79 on day 1 and peaked (6.81±2.37) on day 10 in the experimental group; the value in the control group was 2.81±0.86 on day 1. It decreased significantly and reached the minimum (0.91±0.53) on day 10 (P<0.05). The experimental group had a lower FN incidence than the control group (P<0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 vs. 8.7, P=0.958) or OS (23.9 vs. 17.3, P=0.325) over an 18.6-month median follow-up time. Conclusion PEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.

Clinical Significance of Frailty on Treatment Outcome in Nongeriatric Patients With Head and Neck Cancer and Esophageal Cancer Undergoing Curative-Intent Concurrent Chemoradiotherapy

Background Whether the prevalence of frailty and its clinical significance are relevant to treatment outcomes in younger (aged < 65 years) cancer patients remains uncertain. This study aimed to evaluate the impact of frailty on treatment outcomes in younger cancer patients with head and neck and esophageal malignancy. Material and methods This multicenter prospective study recruited 502 patients with locally advanced head and neck and esophageal cancer during 2016–2017 in Taiwan, aged 20–64 years who received curative-intent concurrent chemoradiotherapy (CCRT) as first-line antitumor treatment. Baseline frailty assessment using geriatric assessment (GA) was performed for each patient within 7 days before CCRT initiation. Results Frailty was observed in 169 (33.7%) of 502 middle-aged patients. Frail patients had significantly higher incidences of chemotherapy incompletion (16.6% versus 3.3%, P < .001) and radiotherapy incompletion (16.6% versus 3.6%, P < .001) than fit patients. During CCRT, frail patients had a significantly higher percentage of hospitalizations (42.0% versus 24.6%, P < .001) and a trend toward a higher percentage of emergency room visits (37.9% versus 30.0%, P = .08) than fit patients. Frail patients more likely had a significantly higher incidence of grade ≥ 3 adverse events than fit patients during CCRT. The 1-year survival rate was 68.7% and 85.2% (hazard ratio 2.56, 95% confidence interval 1.80–3.63, P < .001) for frail and fit patients, respectively. Conclusions This study demonstrated the significance of pretreatment frailty on treatment tolerance, treatment-related toxicity, and survival outcome in younger patients with head and neck and esophageal cancer undergoing CCRT. While GA is commonly targeted toward the older population, frailty assessment by GA may also be utilized in younger patients for decision-making guidance and prognosis prediction.

OUTCOME OF PATIENTS TREATED WITH BLADDER PRESERVATION PROTOCOL IN UROTHELIAL CARCINOMA OF URINARY BLADDER

Objective: To explore trimodality treatment with neoadjuvant chemotherapy followed by concurrent chemoradiotherapy as an alternative approach to neoadjuvant chemotherapy followed by radical cystectomy, for the treatment of non-metastatic muscle invasive bladder carcinoma. Study Design: Retrospective observational study. Place and Duration of Study: Combined Military Hospital Rawalpindi Pakistan, from 2006 and 2015. Methodology: A total of 122 patients were evaluated in a retrospective manner. Primary endpoint was overall survival. Patients received four courses of neoadjuvant chemotherapy followed by radical concurrent chemoradiotherapy with Cisplatin as radiation sensitizer. Result: 5-year overall survival was 80 (66%) in this population and a complete response following completion of treatment was seen in 93 (76.3%) patients. Subset analysis showed markedly increased 5-year overall survival of around 104 (85%) in patients having complete response after neoadjuvant chemotherapy. Conclusion: The study concludes that bladder preservation is an acceptable alternative to radical cystectomy in selected population especially among those who had a complete response to the initial four courses of chemotherapy.

Correlation Between Changes of Pelvic Bone Marrow Fat Content and Hematological Toxicity in Concurrent Chemoradiotherapy for Cervical Cancer

Objectives: To quantify the pelvic bone marrow (PBM) fat content changes receiving different radiation doses of concurrent chemoradiotherapy for cervical cancer and to determine association with peripheral blood cell counts. Methods: Fifty-four patients were prospectively collected. Patients underwent MRI iterative decomposition of water and fat with echo asymmetrical and least squares estimation (IDEAL IQ) scanning at RT-Pre, RT mid-point, RT end, and six months. The changes in proton density fat fraction (PDFF%) at 5–10 Gy, 10–15 Gy, 15–20 Gy, 20–30 Gy, 30–40 Gy, 40–50 Gy, and >50 Gy doses were analyzed. Spearman’s rank correlations were performed between peripheral blood cell counts versus the differences in PDFF% at different dose gradients before and after treatment. Results: The lymphocytes (ALC) nadirs appeared at the midpoint of radiotherapy, which was only 27.6% of RT-Pre; the white blood cells (WBC), neutrophils (ANC), and platelets (PLT) nadirs appeared at the end of radiotherapy which was 52.4%, 65.1%, and 69.3% of RT-Pre, respectively. At RT mid-point and RT-end, PDFF% increased by 46.8% and 58.5%, respectively. Six months after radiotherapy, PDFF% decreased by 4.71% under 5–30 Gy compared to RT-end; while it still increased by 55.95% compared to RT-Pre. There was a significant positive correlation between PDFF% and ANC nadirs at 5–10 Gy (r = 0.62, P = 0.006), and correlation was observed between PDFF% and ALC nadirs at 5–10 Gy (r = 0.554, P = 0.017). Conclusion: MRI IDEAL IQ imaging was a non-invasive approach to evaluate and track the changes of PBM fat content with concurrent chemoradiotherapy for cervical cancer. The limitation of low-dose bone marrow irradiation volume in cervical cancer concurrent chemoradiotherapy should be paid more attention.