To establish prediction models to predict 2-year overall survival (OS) and stratify patients with different risks based on radiomics features extracted from magnetic resonance imaging (MRI) and computed tomography (CT) before definite chemoradiotherapy (dCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). Patients with locally advanced ESCC were recruited. We extracted 547 radiomics features from MRI and CT images. The least absolute shrinkage and selection operator (LASSO) for COX algorithm was used to obtain features highly correlated with survival outcomes in the training cohort. Based on MRI, CT, and the hybrid image data, three prediction models were built. The predictive performance of the radiomics models was evaluated in the training cohort and verified in the validation cohort using AUC values. A total of 192 patients were included and randomized into the training and validation cohorts. In predicting 2-year OS, the AUCs of the CT-based model were 0.733 and 0.654 for the training and validation sets. The MRI radiomics-based model was observed with similar AUCs of 0.750 and 0.686 in the training and validation sets. The AUC values of hybrid model combining MRI and CT radiomics features in predicting 2-year OS were 0.792 and 0.715 in the training and validation cohorts. It showed significant differences in 2-year OS in the high-risk and low-risk groups divided by the best cutoff value in the hybrid radiomics-based model. The hybrid radiomics-based model demontrated the best performance of predicting 2-year OS and can differentiate the high-risk and low-risk patients.

TRT is well-tolerated and effective for selected ES-SCLC patients in the modern era of immunotherapy. Prospective trials are still needed to further evaluate the combination of TRT and immunotherapy for patients with ES-SCLC.

PORT significantly improved the DFS and LRFS in patients with N2a2 and significantly improved the DFS, LRFS, and OS in patients with N2b. Patients with N2a1 could not benefit from PORT.

Purpose/Objective(s)Previous studies showed that prophylactic cranial irradiation (PCI) reduced brain metastases and improved overall survival of patients with limited-stage small-cell lung cancer (LS-SCLC). However, brain magnetic resonance imaging (MRI), currently recognized as the preferred modality for brain metastases detection, was not routinely used for staging and reassessment in previous trials. This retrospective study aimed to reevaluate the role of PCI for LS-SCLC patients in the modern MRI era.Materials/MethodsWe retrospectively reviewed LS-SCLC patients treated with definitive chemoradiotherapy (≥4 cycles of chemotherapy and thoracic intensity-modulated radiotherapy [IMRT]) between 2006 and 2014 in our center. Patients who responded to initial therapy were included and subsequently reassessed for brain metastases by MRI. The cumulative incidence of brain metastases was estimated using the Fine-Grey competing risks regression model. The overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox proportional hazards model.ResultsWe enrolled 177 patients in this study, of which 79 were treated by PCI and 98 were not (non-PCI). The median follow-up was 76.0 months (95% confidence interval, 71.2-80.8 months). All patients achieved complete response (n = 50, 28.2%) or partial response (n = 127, 71.8%) to initial chemoradiotherapy. The cumulative incidence of brain metastases in the PCI group was lower than in the non-PCI group (6.6% vs. 30.0% at 2 years, 12.2% vs. 31.0% at 5 years, P = 0.004). 5-year PFS in the PCI group was significantly higher than in the non-PCI group (45.3% vs. 26.5%, P = 0.002). However, 5-year OS of 48.8% and 39.2% in the PCI and non-PCI groups, respectively, were similar (P = 0.255). In the multivariate analysis, treatment response (P<0.001) and PCI (P = 0.038) were independent prognostic factors for PFS. Stratification analysis revealed that PCI did not improve 5-year PFS for patients with partial response to initial therapy (26.6% vs. 19.7%, P = 0.234).ConclusionIn the Modern Era with MRI Surveillance, PCI is associated with a lower incidence of brain metastases and improved PFS while OS benefit wasn't observed. Patients achieving partial response to initial therapy did not gain PFS benefit from PCI. Prospective trials are still needed to further evaluate the utility of PCI for patients with LS-SCLC.

Purpose/Objective(s) Accounting for 13-15% of lung cancer, small cell lung cancer (SCLC) is typically characterized by more extensive local invasion and more frequent metastases compared with other subtypes. Although SCLC is sensitive to chemoradiotherapy, 25% of the patients with limited stage SCLC would meet local regional relapse. Although thoracic radiation had significantly improved local control, primary tumor recurrence is common in clinic. So far, we had little acquaintance of the local relapse details to help us to make progress in the thoracic radiation. To investigate the patterns of patients with local regional recurrence and the prognosis of primary tumor recurrence, we proposed this study. Materials/Methods We searched patients with pathological diagnosis of SCLC, with disease of limited stage, received systemic chemotherapy and thoracic intensity modulate radiotherapy at our center with available follow-up records between August 1st, 2006 and May 31st,2014. Patients with intrapulmonary recurrence or regional lymph nodes recurrence by the last follow up time, without diffused lung metastasis were selected. All the patients received involved field thoracic radiotherapy with dose of 2Gy per fraction per day. Data regarding patient demographics and treatments. The first local recurrent sites were recorded. Local regional relapse time was calculated from the first day of the treatment delivery to the diagnosis of primary tumor or regional lymph nodes. Overall survival was calculated from the first day of the diagnosis of local relapse to the death using Kaplan Meir Method. Results We identified 482 patients with a diagnosis of limited stage SCLC. Among these, 125 patients fulfilled the eligibility criteria. The median dose of radiotherapy is 60Gy. The median local relapse time was 12.97 months. Primary tumor recurrence, ipsilateral hilar and/or mediastinal lymph node recurrence, contralateral hilar and/or lymph node recurrence, and supraclavicular lymph node recurrence, were observed in 92 patients (73.6%), 49 patients (39.2%), 1 patient (0.8%) and 13 patients (10.4%), respectively. There were 26 patients with multisite local recurrence. Out-field relapse was observed in 6 patients (4.8%). The median follows up time was 34.7 months. After second line therapies, the median survival time for these patients diagnosed as recurrent disease was 10.5 months. Of the 92 patients with primary tumor recurrence, 25 patient received re-radiation and 39 patients also met distant metastasis. Median survival time of patients with primary tumor recurrence is slightly shorter than the others (9.9months vs. 12.0months). Conclusion For patients with limited stage SCLC who received chemoradiotherapy, primary tumor recurrence is still the leading course in local regional relapses and accompanied by worse survival. Accordingly, simultaneous integrated boost might be taken into consideration to primary tumor. Involved field radiation is reasonable with low out-field local recurrence.

Purpose/Objective(s) The optimal role of radiotherapy (PORT) after complete thymectomy for thymoma remains controversial. We investigate the role of postoperative radiotherapy in the complete resection of Masaoka-Koga stage Ⅱ/Ⅲ thymoma with precision radiotherapy techniques. Materials/Methods From January 2000 to December 2017, patients with Masaoka-Koga stage Ⅱ/Ⅲ thymoma who underwent complete resection or complete surgical resection and underwent radiotherapy with precision techniques were included and analyzed. Clinical, pathological, therapeutic and follow-up information was collected. Kaplan-Meier estimates of overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS), and univariate and multivariate Cox proportional hazards regression analyses were performed. Results A total of 244 patients met the selection criteria, 142 (58.1%) of whom were received PORT. Of these, 172 (70.5%) patients with stage Ⅱ thymoma, 72 patients (29.5%) with stage Ⅲ. The median follow-up was 76 months. The 5-year and 10-year OS in the surgical and PORT groups were 93.8% vs 95.4% and 83.6% vs 86.9%, respectively (p=0.34), while the DSS was 93.8% vs 99.0% and 86.3% vs 93.9%, respectively (p=0.038), and the DFS was 85.0% vs 76.9% and 75.9% vs 65.5%, respectively (p=0.65). In stage Ⅲ patients,5-year and 10-year OS was 83.0% vs 95.8%, 54.4% vs 84.4% (HR 0.31, p=0.038) and DSS was 83.0% vs 97.6%, 54.4% vs 91.8% (HR 0.14, p=0.002) for surgery alone vs the PORT group. On multivariate analysis, stage Ⅲ was associated with poorer OS (HR 2.36, p=0.045) and DSS (HR 3.61, p=0.020), and PORT were associated with better DSS (HR=0.26, p=0.012). Conclusion Masaoka-Koga stage Ⅱ/Ⅲ thymoma complete resection after radiotherapy with precision radiotherapy techniques resulted in improved DSS but not significant improvement in OS and DFS; Subgroup analysis showed a more pronounced benefit of PORT in stage Ⅲ patients, with benefits in DSS and OS, suggesting that postoperative radiotherapy can be beneficial in more advanced thymoma.

Purpose/Objective(s) Recently published phase III trials showed that postoperative radiotherapy (PORT) did not improve the survival of patients with pN2 non-small-cell lung cancer (NSCLC) after complete resection. However, the effect of PORT for pN2 NSCLC with different EGFR status remains unclear. Materials/Methods From 2010 to 2019, consecutive patients with pN2 NSCLC after complete resection and adjuvant chemotherapy who had detection of EGFR status were retrospectively analyzed. PORT was administered using IMRT at 2 Gy per fraction up to 50 Gy over 5 weeks. Patients were categorized into 4 groups according to EGFR status and treatment: Group 1 (EGFR wild type with PORT), Group 2 (EGFR wild type without PORT), Group3 (EGFR-mutated with PORT), Group 4 (EGFR-mutated without PORT). The Kaplan-Meier method and log-rank test were used to evaluate the disease-free survival (DFS), overall survival (OS), locoregional relapse free survival (LRFS), and distant metastasis free survival (DMFS). Results Totally 575 patients were enrolled. 264 patients (45.9%) were EGFR wild type, including 96 with PORT and 168 without PORT. 311 patients (54.1%) were EGFR-mutated, including 109 with PORT and 202 without PORT. The median DFS was 28.4 months in Group 1 and 17.3 months in Group 2 (HR 0.70, 95% CI 0.52-0.96, p=0.032). The median OS was not reached in Group 1 and Group 2 (HR 0.75, 95%CI 0.46-1.21, p=0.263). LRFS was statistically higher in Group 1 than Group 2 (HR 0.64, 95%CI 0.43-0.96, p=0.041). However, no significant difference was shown in DMFS (HR 0.75, 95%CI 0.54-1.04, P=0.097). Group 3 and Group 4 showed median DFS of 20.2 months and 25.7 months (HR 1.113, 95% CI 0.84-1.53, p=0.402), respectively. The median OS was not reached in either Group 3 or Group 4 (HR 0.64, 95% CI 0.33-1.21, p=0.201). LRFS was not significantly different (HR 0.83, 95% CI 0.53-1.31, p=0.45) in Group3 vs Group4, neither was DMFS (HR 1.15, 95%CI 0.85-1.57, p=0.73). Conclusion For completely resected pN2 NSCLC, PORT can improve DFS and LRFS in EGFR wild type patients. However, PORT may not prolong survival in EGFR-mutated patients. Prospective randomized clinical trials are needed for validation.

Objective:Simultaneous integrated boost radiation technique in limited-stage small cell lung cancer is lack of evidence. This prospective study aims to evaluate whether the simultaneous integrated boost is as efficacious and safe as conventional fractionated radiotherapy.Methods:Patients diagnosed with treatment-naive and confirmed limited-stage SCLC were eligible. Participants were randomly assigned (1: 1) to receive simultaneous integrated boost radiotherapy (PGTV 60.2 Gy/2.15 Gy/28F, PTV 50.4 Gy/1.8 Gy/28F) or conventional fractionated radiotherapy (PTV 60 Gy/2 Gy/30F). The primary endpoint was 2-year progression-free survival, and the secondary endpoints were 2-year overall survival, 2-year local-regional recurrence-free survival and toxicity.Results:Between February 2017 and July 2019, 231 patients were enrolled. We analyzed 216 patients whose follow-up time was more than 2 years or who had died, among whom 106 patients in the conventional fractionated radiotherapy group and 110 patients in the simultaneous integrated boost radiotherapy group. The median follow-up time was 37 months (95% CI: 35.2-38.7). The 2-year progression-free survival rates were 45.2% vs. 38.2%( HR=1.22, 95% CI: 0.87-1.72, P=0.2). The 2-year overall survival rates were 73.5% vs. 60.9%( HR=1.35, 95% CI: 0.90-2.04, P=0.14). The 2-year local-regional recurrence-free survival rates were 68.7% vs. 69.9%( HR=0.98, 95% CI: 0.62-1.56, P=1.0). Multivariate analysis showed that early radiotherapy yielded better 2-year progression-free survival, overall survival and local-regional recurrence-free survival than delayed radiotherapy in two groups ( HR=1.69, 95% CI: 1.18-2.41, P=0.003; HR=1.72, 95% CI: 1.09-2.70, P=0.018; HR=1.66, 95% CI: 1.01-2.73, P=0.046). Tumor staging was an influencing factor of overall survival (stage Ⅲ vs. stage Ⅰ-Ⅱ, HR=3.64, 95% CI: 1.15-11.57, P=0.028). The most common grade 3-4 adverse events were myelosuppression (21.7% vs. 15.4%, P=0.83), radiation pneumonitis (4.7% vs. 2.7%, P=0.44) and radiation esophagitis (3.8% vs. 1.8%, P=0.51). Conclusions:Simultaneous integrated boost radiotherapy yields equivalent efficacy and toxicities to conventional fractionated radiotherapy for limited-stage small cell lung cancer. Early radiotherapy can enhance clinical prognosis.

The recurrence risk of IIIA-N2 NSCLC after complete resection and adjuvant chemotherapy increased to a high level in 18 months and maintained continuously high till 48 months after surgery, which hinted necessity of intensive follow-up during this period of time. This follow-up strategy implied an individualized surveillance for N2 disease which was different from clinical routine, and should be verified in further studies.

Although serum tumor makers of lung cancer, including carcinoembryonic antigen (CEA), Cytokeratin 19 fragment (CYFRA21-1), and carbohydrate antigen 125(CA 125) are widely used for diagnosis, whether they are prognosis predictors is still controversial. Here, we designed this study to gain a better insight into the association between serum tumor markers and the survivals of patients with postoperative IIIA-N2 nonsmall cell lung cancer (NSCLC) after R0 resection. Patients with pathologically confirmed operable stage IIIA-N2 NSCLC, underwent R0 resection in our institution and with available serum CEA, CYFRA21-1, CA125 pretreatment were eligible. Data on demographics, pathological subtypes, postoperative treatments and survivals were collected. All the patients were scored according to their serum CEA, CYFRA21-1 and CA125 and each abnormal marker gets 1 point. Overall survival (OS), progression free survival (PFS), local regional relapse free survival (LRFS) and distant metastasis free survival (DMFS) were calculated from the date of resection. The association between survivals and each serum tumor markers scores is assessed by log-rank test. Cox model is utilized to do multi-variate analysis. From March 2003 to September 2015, 1011 patients fulfilled the enrollment criteria. Six hundred and fifty-three patients were male. The median age was 57 years old (25-80 years old). Six hundred and sixty-six patients were diagnosed as adenocarcinoma and 275 patients were diagnosed as squamous cell carcinoma. In univariate analysis, abnormal CEA was associated with worse 5y OS (P = 0.025), 5y PFS (P = 0.000) and 5y DMFS (P = 0.000) but not associated with 5-year LRFS (P = 0.057). Abnormal CYFRA21-1 brought significantly worse 5y OS(P = 0.000), 5y LRFS(P = 0.000), but not significantly worse PFS(P = 0.218) or DMFS(P = 0.310).For patients with normal and abnormal CA125, 5-year OS were 53.1% and 38.0% (P = 0.000), 5-year PFS were 27.8% and 14.8%(P = 0.000),5-year LRFS were 40.3% and 24.5% (P = 0.000), 5-year DMFS were 32.3% and 21.0%(P = 0.000). In multivariate analysis, associations between single tumor marker and survivals got the same conclusion as the univariate analysis. Therefore, we made a combined model according to the scores of the patients. There were significant differences of 5y OS (63.9% vs.48.0% vs.38.9% P = 0.000), 5yPFS(32.3% vs.25.0% vs.18.0% P = 0.000 5y LRFS (47.7% vs.36.7% vs.27.2% P = 0.000)and 5y DMFS (37.8% vs.30.0% vs.22.0% P = 0.000) among patients with 0 point, 1 point and 2-3 points. Serum CEA, CYFRA 21- 1 and CA125 can be used as prognostic factors of postoperative N2 NSCLC patients. Combinative detection of the three indices can predict OS, PFS, LRFS and DMFS. The combined model is more reliable than a single marker in assessing the prognosis.

Predicting tumor response after chemoradiotherapy in ESCC remains lacking. This analysis aimed to identify preliminary results of Circulating tumor DNA (ctDNA) markers in predicting tumor response after 4-week chemoradiotherapy for ESCC. We consecutively enrolled patients with unresectable esophageal squamous cell carcinoma, staged as clinical stage III, or clinical stage IV consisting of metastatic lymph nodes in the supraclavicular area according to AJCC 8th. Definitive chemoradiotherapy (CRT) were delivered concurrently with S-1 monotherapy or cisplatin plus paclitaxel-based doublet chemotherapy depending on physician's decision. Plasma samples were collected at different time point if obtained (1) pretreatment (pre-CRT), (2) the 4th week during chemoradiotherapy (mid CRT), (3) 4–8 weeks after chemoradiotherapy (post CRT), (4) 4-6 months in early follow-up time, and (5) disease progression. All patients were subjected to next-generation sequencing (NGS) with a 474 cancer-related gene panel. RECIST and computer tomography (CT) simulation at mid CRT evaluated tumor response. This trial was registered with ClinicalTrials.gov, number NCT0414465. We analyzed 79 serial plasma samples from 37 patients. ctDNA was detectable in 73% (27/37), 46% (12/26) and 31% (5/16) of pretreatment, during chemoradiotherapy and postchemoradiotherapy plasma samples. The most commonly mutated genes in our cohort are TP53 (85.7%, 24/28), CDKN2A (17.9%, 5/28), and ATR (17.9%, 5/28). At diagnosis (pre-CRT), median relative ctDNA abundance was associated with higher clinical T stage (T4 vs T3, 0.76 vs 0.18, p = 0.043). ctDNA concentration was significantly higher with increasing clinical stage (stage IV vs stage III, 109.1 vs 53.4, p = 0.042). Blood-based tumor mutation burden (bTMB) was higher with increasing clinical stage but was not statistically significant. A significant association between ctDNA concentration (r = 0.898, p<0.001) and bTMB (r = 0.737, p<0.001) with relative ctDNA abundance were detected at diagnosis. At mid CRT, overall response rate (ORR) was seen in 67.7% (22/33), including four complete response and 18 partial response. Among 25 patients with both plasma samples and CT evaluation at mid CRT, decreased ctDNA concentration was found in 56% (14/25), increased in 8%, and undetectable ctDNA concentration pre and mid CRT in 36% (9/25). In nine patients with persistently undetectable ctDNA concentration, ORR occurred in 77.8% (7/9). While, in 14 patients with decreased ctDNA concentration, 8 (57%) were associated with ORR. As early assessment, four-week CRT was associated with decreased ctDNA burden. The patients with undetectable ctDNA concentration pretreatment may have a better response to CRT due to relatively lower tumor burden. Radiomics analysis of CT simulation would be used to combine ctDNA assessment in predicting response and prognosis in ESCC. And more enrolled cases with long-term follow-up are needed.

For patients with pⅢA-N2 non-small cell lung cancer (NSCLC) receiving complete resection followed by adjuvant chemotherapy, postoperative radiotherapy (PORT) has been widely used to improve locoregional control as well as survival. However, the optimal timing for the initiation of PORT has not been confirmed. We hypothesized that early PORT could provide better survival than later PORT. This study was designed to investigate the ideal timing of PORT in the treatment of completed resected pⅢA-N2 NSCLC. From January 2003 to December 2015, patients with completed resected pⅢA-N2 NSCLC treated with postoperative chemotherapy and PORT were included in this study. Overall survival (OS) was set as the primary endpoint; disease free-survival (DFS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed as secondary end points. X-tile analysis was conducted to identify the optimum cut-off point for time from surgery to the initiation of PORT. Comparisons of baseline characteristics between different groups were performed with Chi-square test. Kaplan-Meier method and log-rank test were used in survival analyses. A total of 256 patients were included in the final analyses. The optimum cut-off point identified by X-tile analysis was 145 days after surgery. The number of patients receiving early PORT (< 145 days) and later PORT (≥ 145 days) were 149 (58.2%) and 107 (41.8%), respectively. No significant differences were detected in the baseline characteristics between the two groups. Compared with the latter group, patients in the early group had significantly better OS (median 102 months vs. 63 months, p = 0.037), while there were no significant differences for DFS (median 21 months vs. 18 months, p = 0.502), LRFS (median 58 months vs. 61 months, p = 0.926) and DMFS (median 31 months vs. 20 months, p = 0.213). Subgroup analyses showed that for patients with poor or poor-moderate differentiated carcinoma (n = 137), early PORT yielded significantly better OS (median 102 months vs. 58 months, p = 0.020) and DMFS (median 36 months vs. 17 months, p = 0.039) compared with later PORT. It was the same situation in patients underwent pneumonectomy (n = 19), the OS (median not reached vs. 26 months, p = 0.032) and DMFS (median 23 months vs. 11 months, p = 0.014) were significantly better in the early PORT group. For pⅢA-N2 NSCLC patients treated with complete resection and adjuvant chemotherapy, the optimal timing for the initiation of PORT should be within 145 days after surgery. Patients with poor or poor-moderate differentiated carcinoma or those underwent pneumonectomy tend to benefit most from early PORT.

A large portion of patients with pIIIA-N2 non-small cell lung cancer (NSCLC) experience local recurrence and distant metastasis after radical surgery despite postoperative adjuvant chemotherapy ± radiotherapy, and the best option for these relapses remains unclear. This study retrospectively analyzed the correlation between follow-up treatment and survival of these patients and explored the optimal therapy for these patients. From January 2003 to January 2015, patients with pIIIA–N2 NSCLC who experienced local recurrence or distant metastasis after radical first-line treatment in our hospital were retrospectively analyzed to find the correlation between the choice of follow-up treatment and survival of the patients. The Kaplan-Meier, Log Rank test, and Cox regression were used for survival analysis and identification of prognostic factors. A total of 739 patients were enrolled for this study, including 440 males and 299 females, aged 25∼80 years old with an average of 57 years. The first-line treatment was surgery alone for 170 (23.00%) of the patients, surgery + adjuvant chemotherapy for 389 (52.64%), surgery + adjuvant radiotherapy for 13 (1.76%), surgery + adjuvant chemoradiotherapy for 167 (22.60%). Recurrences included 141 case of local-regional recurrence (19.08%), 390 cases of distant metastasis (52.77%), and 208 cases of local recurrence + distant metastasis (28.15%). In the follow-up treatment, chemotherapy was performed for 289 patients (39.11%), local radiotherapy for 279 (37.75%), target therapy (TKI) for 195 (26.39%). As a whole, median survival time of the patients was 47.5 months, and the 2-year and 5-year survival rates were 76.4% and 41.8% respectively. Multivariate Cox regression revealed age, KPS, pathological differentiation, pathological T staging, use of radiotherapy after recurrence, use of targeted therapy after recurrence, and type of recurrence as independent prognostic factors affecting survival. Subgroup analysis showed that for patients who had EGFR- or ALK-positive recurrence and received targeted therapy (TKI) after failure of first-line treatment, local radiotherapy in the follow-up treatment brings no significant benefits to survival, and may even have adverse effects on median survival time (53.26 months for those had local radiotherapy vs. 163.88 months for those didn't); but for those who did not receive targeted therapy, local radiotherapy significantly improved OS (median survival time: 59.14 months vs. 34.43 months, p <0.001). For patients with pIIIA–N2 NSCLC who had relapses after first-line radial therapy, local radiotherapy for local recurrence or distant metastasis may improve OS of those who did not receive targeted therapy (TKI) after recurrence, but may have adverse effect on survival of patients who received targeted therapy and is not recommended as follow-up treatment for the latter.

Postoperative radiotherapy is recommended as a regular treatment of Masaoka stage II-III thymoma and thymic carcinoma. Since thymic neoplasms are always with favorable prognosis, decreasing the dose of organs at risk (OAR) is of significance. Even though modern technology is usually utilized, it is hard to draw a definite conclusion which radiation technology is a suitable choice for these patients. To investigate dosimetric characteristic of volume modulate arc therapy (VMAT) and intensity modulated therapy (IMRT), we proposed this study. Twenty patients pathologically diagnosed as thymic epithelial neoplasms including thymoma and thymic carcinoma and previously received R0 resection were enrolled. Patients were immobilized in a supine position and computed tomography (CT) images were obtained at 5mm per slice under free-breathing for plan evaluation. Clinical target volume (CTV) was delineated with 10mm superior-inferior margins and 5mm anterior, posterior and lateral margins with respect to the tumor bed according to perioperative CT images and operation record. Planning target volume (PTV) was delineated with additional 5 mm margins to the CTV. OARs were delineated according to RTOG guidelines. The prescription dose given was 50 Gy, 2 Gy per fraction. For each patient, two plans were implemented:5 field-IMRT and 2 arc-VMAT. Homogeneity index (HI), conformity index (CI), and conformity number (CN) were calculated. Max dose (Dmax), mean dose (Dmean) and volume of certain dose of OARs were recorded. Two-tailed paired t-tests were performed and p values < 0.05 is defined with statistically significant difference. The median volume of PTV was 208.02 ml. Mean CI were 0.94 in both IMRT and VMAT (p = 0.13). Mean CN were 0.78 (±0.07) and 0.82 (±0.06) in IMRT and VMAT (p = 0.0026), respectively. The corresponding HI were 0.11 (±0.03) and 0.09 (±0.02) (p = 0.002). The two technologies achieved similar Dmax of spinal cord (p = 0.76), Dmax of esophagus (p = 0.70), Dmean of esophagus (p = 0.87), V30 and V40 of heart (p = 0.44 and 0.43), and Dmean of heart (p = 0.38). Mean lung doses in VMAT is lower than those in IMRT (8.07±2.24Gy vs. 8.34±2.20 Gy, p = 0.002). Bilateral lungs V5, V10 and V20 showed 40.10±11.44%, 23.73±8.37% and 11.43±4.51% in VMAT. The corresponding parameters in IMRT were 41.99±11.39%; 24.82±8.18% and 12.30±4.48%. The comparisons of V5, V10 and V20 of lungs all showed significant differences between the two techniques (p = 0.000, p = 0.036, p = 0.007). For the Dmax of LAD, VMAT revealed statistically significant dose decrement compared to IMRT (30.79Gy ±19.89vs. 32.31±20.28 Gy p = 0.035). Moreover, the Dmax of trachea was lower in VMAT than that in IMRT (47.28±8.09Gy vs. 48.55±7.21Gy, p = 0.042). VMAT technique provides superiority in dose conformality, uniformity as well as the protection of lungs, trachea and LAD. It is a more favorable choice for postoperative radiation in thymic neoplasms in comparison with IMRT.

To evaluate the effect of PORT on survivals as well as tumor control in patients with pN2 NSCLC after complete resection. From Jan. 2003 to Dec. 2015, patients with resected pN2 NSCLC at our institution were retrospectively studied. PSM analysis was conducted to generate comparable study arms. The effect of PORT on survivals (OS, DFS, LRFS, and DMFS) were evaluated using the Kaplan–Meier method and log-rank tests. Cox's proportional hazards model was used for multivariate analysis. A statistically significant difference was set as p<0.05. Totally 1434 patients were enrolled, including 341 (23.8%) in the PORT group and 1093 (76.2%) in the non-PORT group. The median follow-up time was 41.8 months. Patients treated with PORT had significantly longer OS (p<0.001) and DFS (p=0.001) when compared with the control, as well as LRFS (p<0.001) and DMFS (p=0.015). Multivariate analyses showed that PORT was an independent prognostic factor associating with better OS (HR=0.756, p=0.012). Moreover, we analyzed the effect of PORT on survivals for pⅢA–N2 NSCLC patients who received adjuvant chemotherapy using PSM to balance several covariates. After adjustment, PORT also significantly improved the survivals. The 3- and 5-year OS rates were 72.9% and 56.1%, respectively in the PORT group and were 62.6% and 41.7%, respectively in the control group (p=0.01). The 3- and 5-year DFS rates were 38.9% and 29.5%, respectively in the PORT group and were 21.6% and 13.2%, respectively in the control group (p<0.001). The 3- and 5-year LRFS rates were 59.0% and 43.8% versus 38.3% and 20.5% in the PORT versus control group, respectively(p<0.001). The 3- and 5-year DMFS rates were 44.5% and 33.2% versus 30.6% and 15.0% in the PORT versus control group, respectively (p<0.0001). For NSCLC patients with resected pN2 or pⅢA-N2 receiving adjuvant chemotherapy, PORT can significantly improve the rates of OS, DFS, LRFS and DMFS. A prospective randomized multicenter clinical trial led by our institution is ongoing now.

Systematic inflammation-immune has been showed to play a crucial role in tumorigenesis and progress. This study is to evaluate the impact of radiotherapy on the prognostic value of systematic inflammation-immune in patients with resected non-small cell lung cancer with pathological N2 nodal involvement (pN2-NSCLC). Preoperative systematic inflammation-immune score (SIS) was defined as preoperative peripheral platelet count ×neutrophil count / lymphocyte count. An optimal cutoff value was developed to stratify patients into high and low risk of distant metastasis (DM), disease-relapse and death in our previous publication (Ann Thoracic Surgery) . The impact of radiotherapy on the prognostic value was tested in subgroup analysis. In training group, 660 consecutive patients who had undergone a curative-intent resection were retrospectively reviewed at our institution between January 2006 and March 2015. Univariate and multivariate analyses revealed that the SIS>650×109 was an independent negative predictor for overall survival (OS) (p=0.001, HR=1.859), disease-free survival (DFS) (p=0.013, HR=1.486), distant metastasis-free survival (DMFS) (p=0.007, HR=1.679), and local recurrence-free survival (LRFS) (p=0.041, HR=2.315). When stratified by radiotherapy, subgroup analysis showed no survival differences whether SIS is over or below 650×109 in patients received postoperative radiotherapy (PORT). However, for patients without PORT, SIS>650×109 still independently predicted poor OS (p=0.001, HR=1.596), DFS (p<0.001, HR=1.619), DMFS (p=0.001, HR=1.648), and LRFS (p=0.022, HR=2.640). Similar results were observed in validation group (Table 2 and 3), which consisted of 189 patients with pN2-NSCLC enrolled between January 2009 and March 2014 from a prospective phase III clinical trial (NCT00880971). The preoperative SIS shows significant prognostic value in resected pN2-NSCLC patients, but not in the subgroup of those receiving further PORT. PORT may impact on systematic inflammation-immune status by local effect, and the mechanism needs further study.

To compare the toxicity and preliminary clinical outcome in patients with locally advanced non-small cell lung cancer receiving volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT). A total of 206 patients with unresectable locally advanced non-small cell lung cancer were included in this study. All patients received concurrent or sequential chemoradiotherapy including 67 patients using VMAT and 139 patients using IMRT. Overall, 40.3% of the patients had stage IIIA and 59.7% had stage IIIB disease. 82.5% of patients were treated with RT dose ≥ 60Gy. Concurrent chemoradiotherapy was used in 45.6% patients. The median follow-up was 19 months (2 months- 35 months). Sixteen (23.9%) patients in VMAT group and 41 (29.5%) in IMRT had symptomatic radiation pneumonitis (≥Grade 2). 2 (3.0%) patients in VMAT group and 5 (3.6%) patients in IMRT group had fatal radiation pneumonitis (P=0.973). 20 (29.9%) patients in VMAT group and 33 (23.7%) patients in IMRT group suffered from grade 2 or higher esophagitis (P=0.410). Univariate and multiple logistic regression showed VMAT was not a predictive factor for either radiation pneumonitis or symptomatic radiation pneumonitis. One-year PFS for VMAT and IMRT groups were 56.5% and 59.9%, respectively (P=0.718). One-year OS for VMAT and IMRT groups were 87.9% and 88.4%, respectively (P=0.331). VMAT was well tolerated without increasing the risk of radiation pneumonitis and had promising clinical outcome when compared with IMRT in the thoracic RT of locally advanced non-small cell lung cancer.

This trial was studying how well the combination of chemoradiation or radiation worked in resected locally advanced cancer of the esophagus compared with surgery alone. We randomly assigned patients with pathological stage ⅡB-Ⅲ esophageal squamous cell carcinoma to receive surgery alone or adjuvant radiotherapy alone (54 Gy in 27 fractions, 5 days per week) or postoperative chemotherapy with paclitaxel (135 to 150 mg per square meter of body-surface area) and cisplatin or nedaplatin (50 to 75 mg per square meter of body- surface area) every 21 days and concurrent radiotherapy (50.4 Gy in 28 fractions, 5 days per week). The primary end point was disease free survival. From October 2014 through July 2018, we enrolled 167 patients. 158 patients at least following up 1 year were analyzed, 50 patients in the surgery alone group (S), 51 patients in the adjuvant radiotherapy group (S+RT), 57 patients in the concurrent chemoradiotherapy group (S+CCRT). The median follow up time was 33.6 months. The 2-year DFS were 45.4% in the S, 46.8% in the S+RT and 63.8% in the S+CCRT, respectively (p=0.024). The 2-year OS was 72.0% in the S+CCRT, 68.8% in the S+RT and 54.9% in the S (p=0.032). The most common acute hematological toxic effects were grade 3 to 4 leukopenia (49.2%) and neutropenia (35.1%) in the S+CCRT, which were more than that in the S+RT group (3.9% and 0%, both p<0.001). There was no significant difference with regard to in-field and out-field recurrent rates between S+CCRT and S+RT (p=0.925). The adjuvant radiotherapy and concurrent chemoradiotherapy could statistically improve the disease free survival and overall survival compared with surgery alone.

For resected pathological ⅢA-N2 Non-small-cell Lung Cancer (pIIIA–N2 NSCLC), postoperative radiotherapy (PORT) is recommended after the adjuvant chemotherapy (ACT). However, pIIIA–N2 is a heterogeneous population, and not all patients can benefit from PORT. We tried to establish a prediction model in selecting fit subgroups for postoperative radiotherapy (PORT), by using the simplest existing clinical data without more examination. This study included 886 pIIIA–N2 patients completing radical resection and ACT at the Cancer Hospital, Chinese Academy of Medical Sciences from January 2003 to December 2015. Patients were divided into two groups: Group PORT, comprising of patients that underwent PORT after radical resection and ACT, and Group NON-PORT comprising of a control group of patients who just underwent radical resection and ACT. Accurate clinical lymph node staging is obtained through contrast-enhanced CT and/or PET-CT. Lymph nodes measured in the short axis≥ 10mm on CT or SUV>2.5 on PET-CT were considered as metastases. Using 3D-CRT/IMRT techniques, PORT was given by 2 Gy per fraction to a total dose of 50 Gy. Outcome measured by overall survival (OS). OS risk score was calculated based on the cox model using stata 15.0. Weight was based on the coefficient. We fitted a proportional odds model consisting of three categories: low, middle, and high survival risk. Statistically significant difference was set at P<0.05. The OS risk score index included a summation of the integer scores of the following variables: age, sex, preoperative T staging, preoperative N staging, the pathologic types, cycles of the ACT. OS risk score=-0.32*female +0.01*age + 0.18*cT-2 + 0.64*cT-3 -0.06*cT-4 + 0.42*cN-1 + 0.31 *cN-2 + 0.23*adenocarcinoma + 0.91*other pathologic types -0.29*cycles of the ACT. According to the distribution of risk score, the whole cohort was divided into three groups according to the trivariate: low-risk group (-1.65 to -0.48, n=270), medium-risk group (-0.48 to -0.14, n=269) and high-risk group (-0.14 to 1.54, n= 267). PORT did not improve OS in the low-risk group (HR = 1.18, P = 0.509) and medium-risk group (HR = 0.77, P = 0.268), but tended to improve OS in the high- risk group(HR = 0.71, P = 0.081). The prediction model is valuable in selecting patients with resected pIIIA-N2 NSCLC fit for PORT. Clinicians may consider implementing the OS risk score index and classifications to stratify patients before performing PORT. PORT is recommended for patients with high- risk group. Further research and long-term observation was required.

The role of postoperative radiotherapy (PORT) in patient with stage IIIA-N2 non-small cell lung cancer is still controversial. It is urgent to explore the prognostic factor which might be helpful to make treatment choice. Thyroid transcription factor-1 (TTF-1) is overexpressed in up to 95% of primary lung adenocarcinoma. Several studies stated that TTF-1 is a prognostic factor in NSQ-NSCLC with conflicting results by reasons of different stages and treatments. Here, we conducted this study to gain a better insight into the association between TTF-1 expression and the necessity of postoperative radiotherapy in patients with stage IIIA-N2 lung adenocarcinoma after R0 resection. Patients with pathologically confirmed inoperable stage IIIA-N2 lung adenocarcinoma and underwent R0 resection with or without PORT in our institution were eligible. Data on demographics, histology, invasion, radiotherapy, chemotherapy, and survival were collected.TTF-1 expressions were determined by immunohistochemistry using available specimen after resection. Patients were classified into the TTF-1 overexpression group (TTF-1 : 3+) and TTF-1 not overexpression group (TTF-1 score 0-2+). Overall survival(OS), progression free survival(PFS), local regional relapse free survival(LRFS) and distant metastasis free survival(DMFS) were calculated from the date of resection. The necessity of PORT is assessed by log-rank test. From October 2006 to April 2015,101 patients fulfilled the enrollment criteria. Fifty-seven patients were male and 44 patients were female. The median age was 56 years old (34-74 years old). Negative, score 1+, score 2+ and score 3+ TTF-1 expression were in 8, 8,17, 68 patients, respectively. Median follow up time was 26.8 months. In patients with TTF-1 overexpression, 19 patients received PORT and 49 did not. For these patients, none of the OS(82.9% vs.81.8%,P=0.731), PFS(57.9% vs. 51.5%P=0.518), LRFS(100% vs.97.6%P=0.513) and DMFS(63.2% VS.62.4%P=0.910) were associated with PORT .In patients without TTF-1 expression, patients who received PORT got more favorable OS (50.0% vs.20.8%P=0.137)and PFS(83.3%VS.22.0%,p=0.028) compared with who did not. Moreover, there is no significant differences in LRFS (100% VS 86.5%p=0.395) and DMFS (66.7%vs 47.1%P=0.442) between patients with and without PORT. This retrospective study demonstrates that patients with TTF-1 score 0-2+ might benefit more from postoperative radiotherapy.