Purpose: The study compared interobserver variation in the delineation of the primary tumour (GTVp) and lymph nodes (GTVln) between three different 4DCT reconstruction types; Maximum Intensity Projection (MIP), Mid-Ventilation (Mid-V) and Mid-Position (Mid-P). Material and methods: Seven radiation oncologists delineated the GTVp and GTVln on the MIP, Mid-V and Mid-P 4DCT image reconstructions of 10 lung cancer patients. The volumes, the mean standard deviation (SD) and distribution of SD (SD/area) over the median surface contour were compared for different tumour regions. Results: The overall mean delineated volume on the MIP was significantly larger (p < 0.001) than the Mid-V and Mid-P. For the GTVp the Mid-P had the lowest interobserver variation (SD = 0.261 cm), followed by Mid-V (SD = 0.314 cm) and MIP (SD = 0.330 cm) For GTVln the Mid-V had the lowest interobserver variation (SD = 0.425 cm) followed by the MIP (SD = 0.477 cm) and Mid-P (SD = 0.543 cm). The SD/area distribution showed a statistically significant difference between the MIP versus Mid-P and Mid-P versus Mid-V for both GTVp and GTVln (p < 0.001), with outliers indicating interpretation differences for GTVp located close to the mediastinum and GTVln. Conclusion: The Mid-P reduced the interobserver variation for the GTVp. Delineation protocols must be improved to benefit from the improved image quality of Mid-P for the GTVln. (C) 2017 Elsevier B.V. All rights reserved. Radiotherapy and Oncology 126 (2018) 325-332
Background and purpose: To study whether cytokine markers may improve predictive accuracy of radiation esophagitis (RE) in non-small cell lung cancer (NSCLC) patients. Materials and methods: A total of 129 patients with stage I-III NSCLC treated with radiotherapy (RT) from prospective studies were included. Thirty inflammatory cytokines were measured in platelet-poor plasma samples. Logistic regression was performed to evaluate the risk factors of RE. Stepwise Akaike information criterion (AIC) and likelihood ratio test were used to assess model predictions. Results: Forty-nine of 129 patients (38.0%) developed grade >= 2 RE. Univariate analysis showed that age, stage, concurrent chemotherapy, and eight dosimetric parameters were significantly associated with grade >= 2 RE (p < 0.05). IL-4, IL-5, IL-8, IL-13, IL-15, IL-1 alpha, TGF alpha and eotaxin were also associated with grade >= 2 RE (p < 0.1). Age, esophagus generalized equivalent uniform dose (EUD), and baseline IL-8 were independently associated grade >= 2 RE. The combination of these three factors had significantly higher predictive power than any single factor alone. Addition of IL-8 to toxicity model significantly improves RE predictive accuracy (p = 0.019). Conclusions: Combining baseline level of IL-8, age and esophagus EUD may predict RE more accurately. Refinement of this model with larger sample sizes and validation from multicenter database are warranted. (C) 2018 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 126 (2018) 506-510 This is an openaccess article under the CC BY license (http://creativecommons.orgilicenses/by/4.0/).
Background and purpose: The prognostic significance of circulating tumor cells (CTCs) in head and neck cancer is still under debate, as only a few studies have been reported and limited conclusions are reached. Besides, CTCs' count alone was utilized as an indicator in the previous researches. As a form of 'liquid biopsy', the further identification of genetic or phenotypic biomarkers on CTCs could possibly provide further clinical significance. Materials and methods: The prospective study enrolled 131 patients with nasopharyngeal carcinoma (NPC). CTCs were isolated at baseline and at the end of concurrent chemoradiotherapy, and cyclooxygenase-2 (COX-2) expression status of CTCs was detected by RNA-in situ hybridization (ISH) method. Results were correlated with patient's clinicopathological parameters and treatment outcomes. Univariate and multivariate survival analyses were performed to determine the prognostic significance. Results: COX-2 expression was found in 87/131 (66.4%) patients at baseline and 53/115 (46.1%) patients at the end of concurrent chemoradiotherapy. Patients with post-therapeutic COX-2 expression had significantly poorer treatment response (P = 0.011) and higher risk of tumor relapse (P = 0.026) and metastasis (P = 0.007). Besides, multivariate analysis revealed that post-therapeutic COX-2 expression on CTCs remained an independent prognostic indicator for poorer progression-free survival (HR 2.17, P = 0.019) and overall survival (HR 2.41, P = 0.024). Conclusion: The study demonstrated that post-therapeutic COX-2 expression on CTCs was a novel and promising prognostic indicator for NPC patients. Future studies are needed to validate our findings and further clarify the value of integrating the indicator with current clinical strategies in improving survival of NPC patients. (C) 2018 Elsevier B.V. All rights reserved.
Background and purpose: Complications after stereotactic radiosurgery (SRS) for brain metastases (BMs) were analyzed in detail using our database including nearly 3000 BM patients. Materials and methods: This was an institutional review board-approved, retrospective cohort study using our prospectively accumulated database including 3271 consecutive patients who underwent gamma knife SRS for BMs during the 1998-2016 period. Excluding four patients lost to follow-up, 112 with three-staged treatment and 189 with post-operative irradiation, 2966 who underwent a single-session of SRS only as radical irradiation were studied. Results: The overall median survival time after SRS was 7.8 (95% CI; 7.4-8.1) months. Post-SRS complications occurred in 86 patients (2.9%) 1.9-211.4 (median; 24.0, IQR; 12.0-64.6) months after treatment. RTOG neurotoxicity grades were 2, 3 and 4 in 58, 25 and 3 patients, respectively. Cumulative incidences determined with a competing risk analysis were 1.4%, 2.2%, 2.4%, 2.6% and 2.9% at the 12th, 24th, 36th, 48th and 60th post-SRS month, respectively. Among various pre-SRS clinical factors and radiosurgical parameters, multivariable analyses demonstrated solitary tumor (Adjusted HR; 0.584, 95% CI; 0.3810.894, p = 0.0133), controlled primary cancer (Adjusted HR; 2.595, 95% CI; 1.646-4.091, p < 0.0001), no extra-cerebral metastases (Adjusted HR; 1.608, 95% CI; 1.028-2.514, p = 0.0374), KPS >= 80% (Adjusted HR; 2.715, 95% CI; 1.245-5.924, p = 0.0121) and largest tumor volume >= 3.3 cc (Adjusted HR; 0.516, 95% CI; 0.318-0.836, p = 0.0072) to be independently significant predictors of a higher incidence of complications. Conclusion: The post-SRS complication incidence is acceptably low (2.9%). Meticulous long-term follow-up after SRS is crucial for all patients. (C) 2018 Elsevier B.V. All rights reserved.
Purpose: To develop a predictive model for stratification of patients with pancreatic cancer who may achieve survival benefits from re-irradiation with stereotactic body radiation therapy (SBRT). Methods: The score was developed based on clinical predictors of OS in 31 patients receiving two courses of SBRT with Cox proportional hazards model. Results were then validated in another cohort with 11 participants to assess the performance of the score. Results: In the training cohort, the median BED10 of the first and second SBRT was 59.5 Gy (48-85.5 Gy) and 50.2 Gy (43.7-66.9 Gy) in 5-8 fractions, while in the validation cohort, the median BED10 of the first and second SBRT was 59.5 Gy (52.5-66.9 Gy) and 47.7 Gy (40.6-54.8 Gy) in 5-8 fractions. The interval between the first and second SBRT of the training cohort and validation cohort was 10.5 months (6.1-24.3 months) and 12.8 months (6.5-29.1 months), respectively. Multivariable analysis showed that tumor stage (P = 0.005), BED10 (P = 0.006) and CA19-9 response (P = 0.04) were significantly predictive of overall survival, which formed SCAD score (named after the initials of factors). Patients with the score < 3 points had a superior OS compared with those with the score >= 3 points in the validation cohort (median OS has not been reached vs. 15.9 months, P = 0.032). Conclusions: The SCAD score may have the potential to identify individuals benefiting from re-SBRT and be a step toward more personalized medicine. (C) 2018 Elsevier B.V. All rights reserved.
Background and purpose: To evaluate the safety and efficacy of Total neoadjuvant treatment (TNT) in patients with rectal cancer with high risk factors. Methods and materials: We did this phase 2 trial in patients who were diagnosed with stage II-III rectal cancer with at least one of the high risk factors. Three cycles of induction CAPOX were followed by pelvic radiotherapy of 50.4 Gy/28 fractions and two cycles of concurrent CAPOX. Three cycles of consolidation CAPOX were delivered after radiotherapy. Primary endpoints were pathological complete response (pCR) and R0 resection. Results: Fifty patients were enrolled and 47 patients were evaluable. A total of 34 patients (72.3%) completed 6 to 8 cycles of chemotherapy and 46 patients (98%) completed the planned radiotherapy. 17 patients (36%) achieved a pCR or clinical complete response (cCR). Three cCR patients (6.4%) refused the operation and selected a watch-and-wait approach. The most common grade 3 or worse adverse events were leucopenia (10.6%) and radiation dermatitis (6.4%). The major surgical complications included pelvic abscesses/infection in 2 patients (4.3%), anastomotic leakage and hemorrhage in1 patient (2.2%), respectively, which were all addressed with conservative management. Conclusions: TNT is effective and safe in patients with locally advanced rectal cancer with high risk factors. Long-term efficacies of TNT need to be further evaluated. This trial is registered with Chinese Clinical Trial Registry, number ChiCTR-OIN-17012284. (C) 2018 Published by Elsevier B.V.
Background and purpose: To evaluate the safety profile and efficacy of high-dose (60 Gy) concurrent chemoradiotherapy (CCRT) compared with standard-dose (50.4-54 Gy) CCRT. Materials and methods: Patients with oesophageal squamous cell carcinoma (OSCC) undergoing CCRT were eligible for a propensity score matched cohort (1: 1 for high dose versus standard dose). Adverse events, local control (LC) and overall survival (OS) were assessed. Results: A total of 380 patients with good balance in observed co-variables were enrolled. OS and LC rates of patients receiving high-dose CCRT were significantly higher than those receiving standard-dose CCRT, with the 10-year OS at 24% versus 13.3%, respectively. In contrast, there was a trend towards increased grades 2-3 acute oesophagitis toxicity among patients receiving high-dose versus standard-dose CCRT (37.4% versus 27.9%, respectively). None experienced grade 5 acute oesophagitis and grade 4 acute toxicities were rare. Similar rates of late radiation oesophagitis, radiation pneumonitis, gastrointestinal reactions and haematological toxicities were observed between patients receiving high-dose versus standard-dose CCRT. Six patients (3.2%) receiving high-dose CCRT experienced >grade 3 leucocytopaenia, and two (1.1%) received standard-dose CCRT, whereas none experienced >grade 3 thrombocytopaenia or anaemia. Three patients (2.3%) receiving high-dose CCRT died of infections caused by myelosuppression. Multivariate analysis showed that anaemia is a significant independent predictor of poor prognosis. Conclusions: Compared with standard-dose CCRT, high-dose CCRT yielded more favourable local control and survival outcomes for patients with OSCC. Grades 2-3 acute oesophagitis toxicity in patients undergoing high-dose CCRT increased, whereas severe, life-threatening toxicities (>grade 3) did not. (C) 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Purpose: No prospective randomized trials have been conducted to date to evaluate the efficacy of palliation of pain or jaundice without treatment, definitive concurrent chemoradiotherapy (CCRT), sequential chemotherapy and radiotherapy (CTRT), or chemotherapy (CT) alone for treating unresectable intrahepatic cholangiocarcinoma (ICC). We designed a nationwide, population-based, cohort study to determine the effects of different treatments on patients with unresectable ICC using propensity score matching (PSM) with the Mahalanobis metric. Patients and methods: We classified patients with unresectable ICC from the Taiwan Cancer Registry database into the following 4 treatment groups: group 1, definitive CCRT; group 2, sequential CTRT; group 3, no treatment (palliative therapy for relief of pain, pruritus, or jaundice); and group 4, CT alone. Confounding factors among the 4 treatment groups were minimized through propensity score matching (PSM). Results: After PSM, the final cohort consisted of 844 patients (211 patients in each of the 4 groups). In both univariable and multivariable Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) derived for groups 1 and 2 compared with group 4 were 0.65 (0.59-0.71) and 0.95 (0.83-1.48), respectively. Furthermore, an aHR (95% CI) of 2.25 (1.89-2.67) was derived for significant independent prognostic risk factors for poor overall survival for group 3 compared with group 4. Conclusions: Definitive CCRT is the optimal therapy for patients with unresectable ICC without distant metastasis. (C) 2018 Elsevier B.V. All rights reserved.
Purpose: To investigate the predictive value of the perfusion (Q) single-photon emission computed tomography (SPECT)-weighted dose-function histogram (DFH) obtained mid-treatment (mid-Tx) with radiotherapy (RT) for radiation-induced lung toxicity (RILT) in patients with non-small cell lung cancer (NSCLC). Materials and methods: The study population consisted of NSCLC patients who were undergoing RT treatment and enrolled in prospective imaging studies. Q-SPECT was performed prior to and during RT (at similar to 40-45 Gy). A baseline dose-volume histogram (DVH) and mid-Tx DVH based on simulation CT as well as a baseline DFH and mid-Tx DFH based on Q-SPECT were calculated. Only patients with stage III NSCLC and visible functional lung (FL) changes on the mid-Tx scan were eligible for this enriched analysis. RILT was graded according to a reported scale. Results: Forty-two stage III NSCLC patients met the criteria for inclusion. The accumulative incidence of grade >= 2 RILT was 31% in this high-risk population. Significant differences in functional metrics such as functional lung volume FV5-FV20 at increments of 5 Gy and functional MLD (FMLD) were observed between patients with and without grade >= 2 RILT (p < 0.05). Similar results were also obtained for anatomical metrics from V5-V20 and MLD (p < 0.05). The areas under the receiver operating characteristic curves (AUCs) ranged from 0.724to 0.812 for baseline DVH parameters, from 0.745 to 0.830 for midTx DVH parameters, from 0.764 to 0.878 for baseline DFH parameters, and from 0.767 to 0.891 for mid-Tx DFH parameters. Further principal components analysis showed that the AUCs were 0.814/0.817 and 0.790/0.857 for baseline/mid-Tx DVH and baseline/mid-Tx DFH, respectively. Conclusions: Mid-Tx DFH parameters based on Q-SPECT were significantly elevated in patients with grade >= 2 RILT in this study population. Among the metrics compared, mid-Tx DFH seemed to have better predictive accuracy, but this difference did not reach statistical difference. (C) 2018 Elsevier B.V. All rights reserved.