Search

Background: For patients with esophageal squamous cell carcinoma (ESCC) treated with surgery alone, the incidence of local-regional recurrence remains unfavorable. Postoperative radiotherapy (PORT) has been associated with increased local-regional recurrence-free survival (LRFS), although its application is limited by concerns of PORT-related toxicities. Methods: Among 3591 patients with ESCC analyzed in this study, 2765 patients with T3-4N0 and T1-4N1-3 lesions and specific local-regional status information were analyzed in a subsequent analysis of adjuvant radiation dose (aRTD) effect. Application of the restricted cubic spline regression model revealed a non-linear relationship between aRTD and survival/radiotoxicity. Linear regression analysis (LRA) was performed to evaluate correlations between LRFS and overall survival (OS)/ disease-free survival (DFS). Results: For patients staged T1–2N0, T1–2N1–3, T3–4N0, and T3–4N1–3, 5-year OS in PORT and non-PORT groups were 77.38% vs. 72.91%, p = 0.919, 52.35% vs. 46.60%, p = 0.032, 73.41% vs. 61.19%, p = 0.005 and 38.30% vs. 25.97%, p < 0.001. With aRTD escalation, hazard ratios (HRs) of OS/DFS declined until aRTD exceeded 50Gy, then increased, whereas that of LRFS declined until aRTD exceeded 50 Gy, then remained steady. HR of treatment-related mortality was stable until aRTD exceeded 50 Gy, then increased. LRA revealed strong correlations between LRFS and OS/DFS (r = 0.984 and r = 0.952, respectively). An absolute 1% advancement in LRFS resulted in 0.32% and 0.34% improvements in OS and DFS. Conclusions: An aRTD of 50Gy was well-tolerated, with favorable survival resulting from PORT-related LRFS improvement in patients staged T3–4N0 or T1-4N1–3. Further stratification analyses based on tumor burden would help determine potential PORT-beneficiaries.

Esophageal carcinosarcoma is a rare type of esophageal cancer; however, few studies have investigated the effects of radiotherapy in locally advanced patients. This study aimed to report experience of the safety and efficacy of intensity-modulated radiotherapy for locally advanced esophageal carcinosarcoma and review the literature. By searching the institutional database between January 2010 and December 2020, along with the literature review, 25 patients were eligible for the study. The clinical and radiologic information of all patients with esophageal carcinosarcoma who underwent radiotherapy were collected. Survival outcomes were calculated using Kaplan-Meier plots. In our series, 5 patients were in the curative/neoadjuvant radiotherapy group and 10 patients were in the adjuvant group. Most tumors were protruding (n = 10, 66.7%). All patients underwent intensity-modulated radiotherapy. In the curative/neoadjuvant radiotherapy group, 2 patients underwent concurrent chemoradiotherapy before surgery, and the other three received radiotherapy alone as the initial treatment. The median follow-up time was 43.1 months. All patients showed a partial response at the efficacy evaluation. The median time of overall survival and progression-free survival were 40.2 months (95% confidence interval [CI], 13.1-67.3 months) and 19.0 months (95% CI, 13.9 months-24.1 months) for the entire cohort, but were not reached for curative/neoadjuvant radiotherapy group. Overall survival (hazard ratio [HR] 0.81, 95% CI, 0.15-4.43; P = .805) and progression-free survival (HR 1.68, 95% CI, 0.35-8.19; P = .514) did not differ significantly between the 2 groups. When considering the literature review data in the final analysis, overall survival (HR 0.84, 95% CI, 0.25-2.81; P = .779) and progression-free survival (HR, 0.68; 95% CI, 0.26-1.76; P = .425) were also not different between the 2 groups. Treatment based on intensity-modulated radiotherapy with neoadjuvant or curative intent may be an option for patients with unresectable esophageal carcinosarcoma. Further research with a larger sample size is needed to validate the reliability.

Purpose: Thymic neuroendocrine tumors (TNETs) are a collection of slow-progressing neoplasms located in the anterior mediastinum. Relatively few previously published studies have focused on thymic carcinomas. This study investigated the basic clinical characteristics, treatment, and prognosis of TNETs. Methods: Patients were enrolled in the study from January 2003 to December 2017 who had been diagnosed with TNETs through pathological screening and treated at our institution. Demographic data from each patient, the Masaoka stage, histology and size of the tumor, tumor invasion characteristics, and therapeutic strategies were gathered. The Kaplan–Meier method was used to assess patient survival. In addition, the log-rank test was used to carry out univariate analyses. Results: Twenty-six patients were eligible for inclusion in the study. The median age of the patients was 46.5 (25–69) years. The tumor median maximum diameter was 7.9 cm (from 3 to 19 cm). Twenty-four patients were treated surgically. Nineteen patients completed radiation therapy, and sixteen patients underwent chemotherapy. A median follow-up time of 54.95 months was observed. The survival rate for three years was 75.0% and 70.6% for five years. The corresponding progression-free survival rates for three and five years were 55.7% and 37.7%, respectively. The local, regional recurrence-free survival (LRFS) rates were 87.2% and 81.7%, and the distant metastasis-free survival (DMFS) rates were 55.7% and 37.7%, at three and five years, respectively. Local recurrence (six patients) and bone metastasis (six patients) were observed as the most frequent failures. Conclusion: TNET was observed to be an aggressive but rare malignant lesion. While the predominant treatment was complete resection, chemotherapy and radiotherapy were also required due to the high recurrence rate.

Background Retrospective studies have shown that adjuvant treatment improves survival of patients with stage IIB–III esophageal squamous cell carcinoma, but there is no evidence from prospective trials so far. Materials and Methods Patients with pathological stage IIB–III esophageal squamous cell carcinoma were randomly assigned to receive surgery alone (SA), postoperative radiotherapy (PORT), or postoperative concurrent chemoradiotherapy (POCRT). PORT patients received 54 Gy in 27 fractions; the POCRT group received 50.4 Gy in 28 fractions, plus concurrent chemotherapy with paclitaxel (135–150 mg/m2) and cisplatin or nedaplatin (50–75 mg/m2) every 28 days. The primary endpoint was disease-free survival (DFS), and the secondary endpoint was overall survival (OS). Results A total of 172 patients were enrolled (SA, n = 54; PORT, n = 54; POCRT, n = 64). The 3-year DFS was significantly better in PORT/POCRT patients than in SA patients (53.8% vs. 36.7%; p = .020); the 3-year OS was also better in PORT/POCRT patients (63.9% vs. 48.0%; p = .025). The 3-year DFS for SA, PORT, and POCRT patients were 36.7%, 50.0%, 57.3%, respectively (p = .048). The 3-year OS for SA, PORT, and POCRT patients were 48.0%, 60.8%, 66.5%, respectively (p = .048). Conclusion PORT/POCRT (especially POCRT) may significantly improve DFS and OS in stage IIB–III esophageal squamous cell carcinoma. Implications for Practice The results of this phase III study indicated that postoperative radiotherapy/postoperative concurrent chemoradiotherapy (PORT/POCRT) could significantly improve disease-free survival and overall survival in stage IIB–III esophageal squamous cell carcinoma compared with surgery alone with acceptable toxicities. In-field and out-of-field recurrences were comparable between the POCRT and PORT groups, which demonstrates the rationality and safety of the radiation field used in this study. The postoperative regimens in this trial might be accepted as standard treatment options for pathological stage IIB–III esophageal cancer. Larger sample size prospective randomized trials to identify the value are warranted.

The aim of this study was to compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) staging system with the 8th edition of the American Joint Committee on Cancer (AJCC) staging system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on a substage of the JES staging system. Area under the curve (AUC) values of the receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus PORT [S+RT group]) across substages of the 11th JES staging system according to independent prognostic factors for overall survival (OS) identified using Cox proportional hazards regression. A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC staging system was significantly higher than that for the 11th JES staging system (0.701 vs. 0.675, p

Background To investigate the survival benefit of concurrent chemoradiotherapy (CCRT) for patients with locally advanced esophageal squamous cell carcinoma (ESCC) during the years of intensity‐modulated radiotherapy (IMRT). Methods Medical records of 1089 patients with ESCC who received IMRT from January 2005 to December 2017 were retrospectively reviewed. A total of 617 patients received CCRT, 472 patients received radiotherapy (RT) alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterward. Results After a median follow‐up time of 47.9 months (3.2–149.8 months), both overall survival (OS) and progression‐free survival (PFS) of the CCRT group were better than those of the RT alone group, either before or after PSM. After PSM, the 1‐, 3‐, and 5‐year OS of RT alone and CCRT groups were 59.0% versus 70.2%, 27.7% versus 40.5% and 20.3% versus 33.1%, respectively (p, Concurrent chemoradiotherapy versus radiotherapy alone in the era of intensity modulated radiotherapy retrospective analysis of more than 1000 patients.

To determine the survival and prognostic factors of esophageal squamous cell carcinoma (ESCC) patients undergoing radical (chemo)radiotherapy in the era of three-dimensional conformal radiotherapy (3DCRT) and intensity modulated radiotherapy (IMRT) in China.The Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) conducted the first nationwide survey of nine institutions. Detailed information was accumulated on 5185 patients with ESCC who received definitive 3DCRT/IMRT between 2002 and 2018. Relevant prognostic factors were evaluated to assess their influence on overall and progression-free survivals.After a median follow-up time of 47.0 (0.9-157.4) months, the 1-year, 2-year, 3-year and 5-year overall survival rates of the whole group were 69.8%, 46.6%, 37.9% and 30.1%. The 1-year, 2-year, 3-year, and 5-year progression-free survival rates were 54.1%, 36.6%, 30.5% and 24.9%. Multivariate analysis demonstrated that sex, clinical stage, treatment modality and radiation dose were prognostic factors for OS. The survival of patients who received concurrent chemoradiotherapy (CCRT) was better than that of patients who received radiotherapy alone or sequential chemoradiotherapy. Patients receiving adjuvant chemotherapy after CCRT had a better OS than patients receiving CCRT alone. Patients receiving higher radiation dose had a better OS than those patients receiving low-dose radiotherapy.The survival of ESCC patients undergoing radical (chemo)radiotherapy was relatively satisfactory in the era of 3DCRTand IMRT. As the largest-scale multicenter research on esophageal cancer radiotherapy conducted in China, this study establishes national benchmarks and helps to provide references for subsequent related researches.

Background Concurrent epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKI) with radiotherapy in patients with EGFR‐mutant unresectable stage III non‐small cell lung cancer (NSCLC) might improve survival. However, both treatments carry a potential risk of pneumonitis. Methods Between May 2012 and December 2017, patients with unresectable stage III NSCLC treated with concurrent radiotherapy and EGFR‐TKI were enrolled in this retrospective study. The baseline characteristics were evaluated to determine correlations with toxicity development. Results Among 45 eligible patients, 20 (44.4%) had an EGFR mutation and 44 (97.8%) received 50–66 Gy of radiotherapy. The median follow‐up was 62.7 months. The median progression free survival (PFS) and overall survival (OS) for patients with EGFR‐mutations were 27.9 (95% CI: 18.7–37.2) and 49.7 (95% CI: 27.7–71.8) months, and 13.8 (95% CI: 8.8–18.9) and 31.1 (95% CI: 9.8–52.4) months for EGFR wild‐type/unknown patients. A total of 17 patients (37.7%) developed radiation pneumonitis/pneumonitis (14 grade 2, 3 grade 3). In 16 patients, pneumonitis occurred within the radiation field and one patient had bilateral pneumonitis. The median time from the initial radiotherapy to pneumonitis was 74 days. Logistic regression analysis revealed a trend between the time of EGFR‐TKI and the development of G2+ pneumonitis. For late toxicity, only two patients had G2+ fibrosis. The daily dyspnea symptoms of patients with G2+ pneumonitis recovered significantly after the phase of pneumonitis (P = 0.007). Conclusions Combined EGFR‐TKI and radiotherapy showed favorable survival in EGFR‐mutant patients with inoperable stage III NSCLC, with a 6.7% incidence of grade 3 radiation pneumonitis/pneumonitis, despite a higher incidence of mild‐to‐moderate radiation pneumonitis. Key points Significant findings of the study We evaluated the outcomes and radiation pneumonitis after EGFR‐TKI during interval radiotherapy. EGFR‐TKI plus radiotherapy increased survival in patients with EGFR‐mutant inoperable stage III NSCLC. The mild‐to‐moderate radiation pneumonitis incidence increased but no grade 4–‐5 adverse events occurred. What this study adds The combination of EGFR‐TKI and radiotherapy might carry a risk of pneumonitis; however, there are limited data concerning dose constraints. Our results showed a slightly higher incidence of mild or moderate radiation pneumonitis by strict dose limitation., Our study evaluated the outcomes and radiation pneumonitis which occurred in patients following EGFR‐TKI during interval radiotherapy. The results of combined EGFR‐TKI and radiotherapy showed favorable survival in EGFR‐mutant patients with inoperable stage III NSCLC, a higher incidence of mild to moderate radiation pneumonitis was observed and no grades 4‐5 adverse events occurred.

Performance of thoracic radiotherapy may be assisted by the use of thoracoabdominal flat immobilization devices (TAFIDs) and integrated cervicothoracic immobilization devices (ICTIDs). This study was performed to compare setup errors of TAFIDs and ICTIDs. Forty-four patients with lung cancer were retrospectively reviewed; 22 patients were immobilized with a TAFID and 22 with an ICTID. In total, 343 cone-beam computed tomography images of these patients were collected for radiotherapy setup. The 3-dimensional setup errors and the displacement of the acromioclavicular joint against the supraclavicular region were calculated. An independent-samples t-test and rank-sum test were used for statistical analyses. The translational setup errors of the TAFID group vs ICTID group in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were 0.14 ± 0.17 vs 0.14 ± 0.16 cm (p = 0.364), 0.23 ± 0.26 vs 0.15 ± 0.15 cm (p = 0.000), and 0.16 ± 0.15 vs 0.12 ± 0.14 cm (p = 0.049), respectively. The relative displacement of the acromioclavicular joint against the supraclavicular joint in the LR, SI, and AP directions were 0.10 ± 0.12 vs 0.09 ± 0.10 cm (p = 0.176), 0.13 ± 0.13 vs 0.11 ± 0.12 cm (p = 0.083), and 0.17 ± 0.16 vs 0.12 ± 0.11 cm (p = 0.001), respectively. The overall displacement of the supraclavicular region was 0.28 ± 0.19 vs 0.23 ± 0.15 cm (p0.001). The recommended planning target volume margins in the LR, SI, and AP directions were 0.46 vs 0.74 cm, 0.51 vs 0.47 cm, and 0.49 vs 0.41 cm, respectively. For patients with lung cancer, using an ICTID can reduce setup errors in the SI direction and displacements of the acromioclavicular joint and supraclavicular region compared with a TAFID. Therefore, an ICTID is preferred for patients with lung cancer with supraclavicular target volume.

Background Currently, adjuvant therapy is not recommended for patients with thoracic esophageal squamous cell cancer (TESCC) after radical surgery, and a proportion of these patients go on to develop locoregional recurrence (LRR) within 2 years. Besides, there is no evidence for salvage chemoradiation therapy (CRT) in patients with residual tumor after esophagectomy (R1/R2 resection). In addition, factors like different failure patterns and relationship with normal organs influence the decision for salvage strategy. Here, we aimed to design a modularized salvage CRT strategy for patients without a chance of salvage surgery according to different failure patterns (including R1/R2 resection), and further evaluated its efficacy and safety. Methods Our study was designed as a one arm, multicenter, prospective clinical trial. All enrolled patients were stratified in a stepwise manner based on the nature of surgery (R0 or R1/2), recurrent lesion diameter, involved regions, and time-to-recurrence, and were further assigned to undergo either elective nodal irradiation or involved field irradiation. Then, radiation technique and dose prescription were modified according to the distance from the recurrent lesion to the thoracic stomach or intestine. Ultimately, four treatment plans were established. Discussion This prospective study provided high-level evidence for clinical salvage management in patients with TESCC who developed LRR after radical surgery or those who underwent R1/R2 resection. Trial registration Prospectively Registered. ClinicalTrials.govNCT03731442, Registered November 6, 2018.

Background Information on the optimal salvage regimen for recurrent esophageal cancer is scarce. We aimed to assess the patterns of locoregional failure, and evaluate the therapeutic efficacy of salvage therapy along with the prognostic factors in recurrent thoracic esophageal squamous cell carcinoma (TESCC) after radical esophagectomy. Methods A total of 193 TESCC patients who were diagnosed with recurrence after radical surgery and received salvage treatment at our hospital were retrospectively reviewed from 2004 to 2014. The patterns of the first failure were assessed. The post-recurrence survival rate was determined using the Kaplan-Meier method and analyzed using the log-rank test. Multivariate prognostic analysis was performed using the Cox proportional hazard model. Results The median time of failure was 7.0 months. Among the 193 patients, 163 exhibited isolated locoregional lymph node (LN) recurrence and 30 experienced locoregional LN relapse with hematogenous metastasis. Among the 193 patients, LN recurrence was noted at 302 sites; the most common sites included the supraclavicular (25.8%; 78/302) and mediastinal LNs (44.4%; 134/302), particularly stations 1 to 6 for the mediastinal LNs (36.4%; 110/302). The median overall survival (OS) was 13.1 months after recurrence. In those treated with salvage chemoradiotherapy, with radiotherapy, and without radiotherapy, the 1-year OS rates were 68.5, 55.0, and 28.6%; the 3-year OS rates were 35.4, 23.8, and 2.9%; and the 5-year OS rates were 31.8, 17.2, 2.9%, respectively (P P = 0.044). Multivariate analysis showed that the pathological TNM stage and salvage treatment regimen were independent prognostic factors. Conclusions Supraclavicular and mediastinal LN failure were the most common types of recurrence after R0 surgery in TESCC patients. Salvage chemoradiotherapy or radiotherapy could significantly improve survival in esophageal cancer with locoregional LN recurrence.

Background Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0–28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer. Method This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135–150 mg/m2) plus cisplatin or nedaplatin (50–75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT. Discussion This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma. Trial registration clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.

Background The low incidence of primary mediastinal seminomas has precluded the development of clinical trials on mediastinal seminomas. We investigated the clinicopathologic characteristics, prognosis of patients with primary mediastinal seminomas as well as the efficiency of nonsurgical treatments compared with treatments containing surgery. Methods We retrospectively collected data on the clinicopathologic characteristics, treatments, toxicities, and survival of 27 patients from a single center between 2000 and 2018. Patients were divided into two groups according to whether they received operation. Survivals were assessed using the Kaplan–Meier method. Univariate analysis was performed using the log-rank test. Results The median age was 28 (13–63) years. The most common symptoms were chest pain (29.6%), cough (25.9%), and dyspnea (22.2%). There were 13 and 14 patients in surgery and non-surgery group. Patients in the non-surgical group were more likely to be with poor performance scores (100% vs. 76.9%) and disease invaded to adjacent structures (100% vs. 76.9%) especially great vessels (100% vs. 46.2%).The median follow-up period was 32.23 (2.7–198.2) months. There was no significant difference of overall survival (5-year 100% vs. 100%), cancer-specific survival (5-year 100% vs. 100%), local regional survival (5-year 91.7% vs. 90.0%, p = 0.948), distant metastasis survival (5-year 90.9% vs. 100.0%, p = 0.340) and progression-free survival (82.5% vs. 90.0%, p = 0.245) between patients with and without surgery. Conclusions Primary mediastinal seminoma was with favorable prognosis, even though frequently invasion into adjacent structures brings difficulties to surgery administration. Chemoradiotherapy is an alternative treatment with both efficacy and safety.

Background This study aimed to establish a predictive nomogram integrating epidermal growth factor receptor (EGFR) mutation status for 3‐ and 5‐year overall survival (OS) in unresectable/inoperable stage III non‐small cell lung cancer (NSCLC) treated with definitive chemoradiotherapy. Methods A total of 533 stage III NSCLC patients receiving chemoradiotherapy from 2013 to 2017 in our institution were included and divided into training and testing sets (2:1). Significant factors impacting OS were identified in the training set and integrated into the nomogram based on Cox proportional hazards regression. The model was subject to bootstrap internal validation and external validation within the testing set and an independent cohort from a phase III trial. The accuracy and discriminative capacity of the model were examined by calibration plots, C‐indexes and risk stratifications. Results The final multivariate model incorporated sex, smoking history, histology (including EGFR mutation status), TNM stage, planning target volume, chemotherapy sequence and radiation pneumonitis grade. The bootstrapped C‐indexes in the training set were 0.688, 0.710 for the 3‐ and 5‐year OS. For external validation, C‐indexes for 3‐ and 5‐year OS were 0.717, 0.720 in the testing set and 0.744, 0.699 in the external testing cohort, respectively. The calibration plots presented satisfying accuracy. The derivative risk stratification strategy classified patients into distinct survival subgroups successfully and performed better than the traditional TNM staging. Conclusions The nomogram incorporating EGFR mutation status could facilitate survival prediction and risk stratification for individual stage III NSCLC, providing information for enhanced immunotherapy decision and future trial design., The nomogram incorporating EGFR mutation status which could facilitate the 3‐ and 5‐year overall survival prediction for individual stage III NSCLC patients treated with definitive chemoradiotherapy. The derivative risk stratification could successfully classify patients into distinct outcome groups and provide information to enhance immunotherapy decision and future trial design.

Background: EGFR tyrosine kinase inhibitor (TKI) is recommended as the first-line therapy for patients with EGFR-mutant metastatic non-small cell lung cancer (NSCLC). Yet, resistance often occurs in 1 year after therapy and most progressions occur at the initial sites of disease. Addition of local therapy to the first-line TKI therapy may delay the progression and provide survival benefit to the patients. Methods: From 2010 to 2017, metastatic NSCLC patients with EGFR activating mutations who received first-line TKI and relatively radical local therapy (RRLT) were reviewed. RRLT was defined as local curative therapy to the main site or any intensity of local therapy to all sites of disease. The Kaplan-Meier method and log-rank test were used for survival estimation and comparison. Results: A total of 45 patients were included in this retrospective study with a median follow-up of 48.0 months. The median progression-free survival (PFS) and overall survival (OS) was 17.0 months (95% confidence interval [CI]: 14.6-19.3) and 55.0 months (95% CI: 49.3-60.6), respectively. Univariate analysis indicated that age ⩽ 60 years ( P = .019), first-line TKI duration ⩾ 10 months ( P = .028), and accumulated TKI duration ⩾ 20 months ( P = .016) were significantly associated with favorable OS. Among the 36 patients who progressed during the follow-up, 55.8% of the progressions occurred at the new sites. RRLT combined with TKI did not show any severe toxicity to the patients. Conclusions: Combined application of RRLT and first-line TKI may improve the survival and alter the pattern of failure for metastatic NSCLC patients with EGFR activating mutations.

Purpose To investigate the interobserver variability (IOV) in target volume delineation of definitive radiotherapy for thoracic esophageal cancer (TEC) among cancer centers in China, and ultimately improve contouring consistency as much as possible to lay the foundation for multi-center prospective studies. Methods Sixteen cancer centers throughout China participated in this study. In Phase 1, three suitable cases with upper, middle, and lower TEC were chosen, and participants were asked to contour a group of gross tumor volume (GTV-T), nodal gross tumor volume (GTV-N) and clinical target volume (CTV) for each case based on their routine experience. In Phase 2, the same clinicians were instructed to follow a contouring protocol to re-contour another group of target volume. The variation of the target volume was analyzed and quantified using dice similarity coefficient (DSC). Results Sixteen clinicians provided routine volumes, whereas ten provided both routine and protocol volumes for each case. The IOV of routine GTV-N was the most striking in all cases, with the smallest DSC of 0.37 (95% CI 0.32–0.42), followed by CTV, whereas GTV-T showed high consistency. After following the protocol, the smallest DSC of GTV-N was improved to 0.64 (95% CI 0.45–0.83, P = 0.005) but the DSC of GTV-T and CTV remained constant in most cases. Conclusion Variability in target volume delineation was observed, but it could be significantly reduced and controlled using mandatory interventions.

BackgroundThe aim of this study was to compare the effects of simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) and conventional fractionated-IMRT (CF-IMRT) for patients with esophageal squamous cell carcinoma (ESCC).MethodsThe data of 1173 patients treated with either CF-IMRT or SIB-IMRT for a curative intent from 2005 to 2016 were retrospectively reviewed. Propensity score matching (PSM) was used to create a well-balanced cohort of 687 patients at 1:2 ratio (237 patients in SIB-IMRT group and 450 patients in CF-IMRT group). Overall survival (OS), progression-free survival (PFS), recurrence pattern, and toxicity profiles were evaluated and compared between the two groups after PSM.ResultsAfter a median follow-up time of 42.3 months (range, 3.0-153.2 months) for surviving patients, survival results were comparable in the two groups. After PSM, the 1-year, 2-year and 4-year OS rates in the SIB-IMRT and CF-IMRT groups were 70.0% vs. 66.4%, 41.9% vs. 41.7% and 30.2% vs. 27.6%, respectively (p = 0.87). The 1-year, 2-year and 4-year PFS rates were 48.4% vs. 49.1%, 31.2% vs. 29.4%, and 26.1% vs. 17.9%, respectively (p = 0.64). Locoregional recurrence (p = 0.32) and distant metastasis (p = 0.54) rates were also comparable between two groups. The toxicity profile was similar in the two groups. Multivariate analyses in the matched samples showed that female, concurrent chemotherapy and earlier clinical stage were independently associated with longer OS and PFS.ConclusionsSIB-IMRT appears to be equivalent to CF-IMRT in treatment efficacy and safety, and could become an alternative option for definitive radiotherapy of ESCC.

Background Surveillance was recommended for patients after R0 esophagectomy by National Comprehensive Cancer Network (NCCN) guidelines. However, local failure was high in locally advanced patients (48–78%). The present study aimed to determine whether adjuvant treatment improved survival for stage IIb-III thoracic esophageal squamous cell carcinoma (TESCC). Methods A retrospective review of patients diagnosed as esophageal carcinoma at the Chinese Academy of Medical Sciences Cancer hospital, between January 2004 and December 2011, was performed. A database compiling 975 patents with node positive or stage III thoracic esophageal carcinoma after R0 surgery with or without postoperative radiation/chemoradiation was created. A 1:1 matched study group was generated by the Greedy method after propensity score matching (PSM) analysis. Survival curves were calculated by the Kaplan–Meier method and compared with the log-rank test. Univariate and multivariate analyses were using the Cox proportional hazards regression model. Results 975 patients were enrolled in the study, 510 patients (52.3%) did not receive any postoperative treatment after R0 surgery and 465 patients had either postoperative chemoradiation or radiotherapy. Median follow-up was 69.2 months. After PSM, 222 well-balanced patients in each group demonstrated the same results. The 3-year, 5-year survival rates and median survival in surgery group (33.0%, 26.4%, 24.3 months) were inferior to those in postoperative treatment group (48.3%, 37.1% and 34.3 months), ( P = 0.002). Compared with radiotherapy, postoperative chemoradiation did not improve DFS and OS ( P = 0.692; P = 0.368). N stage and adjuvant treatment are independent prognostic factors. Conclusions Adjuvant treatment could improve survival for patients with stage IIb-III TESCC.

Introduction: The high intracranial efficacy of EGFR-TKI challenges the role of upfront intracranial radiation therapy (RT) in non-small cell lung cancer (NSCLC) patients with EGFR mutation and brain metastases (BM). Therefore, we conducted a retrospective analysis to demonstrate the role of upfront RT in these patients. Materials and Methods: Patients that had histologically confirmed NSCLC with EGFR mutation, brain metastases, and received TKI or upfront RT with TKI were included in this study. Intracranial progression was estimated using the Fine-Gray competing risks model. Kaplan-Meier analysis and Log-rank test were used to evaluate and compare intracranial progression-free survival (iPFS), systemic PFS (sPFS), time to second-line systematic therapy (SST) and overall survival (OS). Results: Among the 93 patients included, 53 patients received upfront RT and TKI, and 40 patients received TKI only. Upfront RT group showed lower intracranial progression risk with adjusted SHR 0.38 (95% CI, 0.19 to 0.75, P= 0.006) and longer median time to sPFS (15.6 vs 8.9 months, P= 0.009). There were 9 out of 36 (25%) and 16 out of 34 (47.1%) patients who had oligo-progression received salvage RT in the RT group and TKI group, respectively. After the salvage RT, upfront RT did not prolong the median time to SST (23.6 vs 18.9 months, P=0.862) and OS (median time, 35.4 vs 35.8 months, P=0.695) compared to TKI alone. Conclusion: Compared to upfront intracranial RT, the salvage RT to oligo-progressive disease allowed patients getting TKI to have similar time on initial TKI and OS despite worse iPFS. The best timing of intracranial RT remains to be further verified.

Aim The need or otherwise for lateral pelvic node dissection (LPND) in rectal cancer patients with clinical lateral pelvic node metastasis (LPNM) after neoadjuvant chemoradiotherapy (nCRT) is controversial. This study was designed to explore the predictive factors for pathological LPNM in rectal cancer patients with clinical LPNM after nCRT. Method From January 2010 to February 2018, a consecutive series of patients with rectal cancer and clinical LPNM after nCRT who underwent total mesorectal excision and LPND were reviewed. Patient demographics, operative and pathological outcomes were collected and analysed. Results A total of 76 consecutive cases were included in this study: 53 (69.7%) patients underwent unilateral LPND and 23 (30.3%) bilateral LPND. The pathological results showed that LPNM was found in 13 (17.1%) patients. Multivariate logistic regression analysis showed that the post-nCRT lateral pelvic node size ≥ 5 mm (OR = 7.67, 95% CI = 1.45-40.63, P = 0.017) and mucinous/signet-ring adenocarcinoma (OR = 4.60, 95% CI = 1.11-19.08, P = 0.035) were independent risk factors for pathological LPNM. Conclusion Post-nCRT lateral pelvic node size ≥ 5 mm and mucinous/signet-ring adenocarcinoma were independent predictive factors of pathological LPNM for rectal cancer patients with clinical LPNM after nCRT, and patients with these characteristics may benefit from LPND.

Objective To investigate the safety and efficacy of nimotuzumab combined with radiotherapy for elderly patients with non-resectable esophageal carcinoma (EC). Methods Eligible patients were aged 70 years or older and had treatment-naive, histologically proven inoperable locally advanced EC. Enrolled patients received radiotherapy with a total dose of 50-60 Gy in 25-30 fractions, concurrent with weekly infusion of nimotuzumab. The primary end point was the rate of more than grade 3 toxicities. Results From June 2011 to July 2016, 46 patients with stage II-IV EC with a median age of 76.5 years were enrolled. There were 10, 28 and 8 patients with stage II, III and IV disease, respectively. The common acute toxicities included esophagitis (grade 1-2, 75.4%; grade 3, 8.7%), pneumonitis (grade 1, 4.3%; grade 2, 6.5%; grade 3, 2.2%), leukopenia (grade 1-2, 60.9%; grade 3-4, 4.4%), gastrointestinal reaction (grade 1-2, 17.3%; grade 3, 2.2%), thrombocytopenia (grade 1-2, 21.7%; grade 3, 2.2%), and radiothermitis (grade 1-2, 39.2%). The incidence of grade 3-4 adverse effects was 17.4%. No grade 5 toxicities were observed. Clinical complete response, partial response, stable disease, and progressive disease were observed in 1 (2.2%), 31 (67.4%), 12 (26.1%), and 2 (4.3%) patients, respectively. The median overall survival (OS) and progression-free survival (PFS) were 17 and 10 months, respectively. The 2-, 3-, and 5-year OS and PFS rates were 30.4%, 21.7%, 19.6%, and 26.1%, 19.6%, 19.6%, respectively. Conclusions Nimotuzumab combined with radiotherapy is a safe and effective therapy for elderly patients who are not surgical candidates. Further studies are warranted to confirm its therapeutic effects in elderly EC patients.

PURPOSE/OBJECTIVE(S) A reliable model is needed to estimate the risk of postoperative recurrence and the benefits of postoperative radiotherapy (PORT) in patients with thoracic esophageal squamous cell cancer (TESCC). MATERIALS/METHODS The study retrospectively reviewed 3652 TESCC patients in stage I-III after radical esophagectomy, with or without PORT. In one institution as the training cohort (n = 1620), independent risk factors associated with locoregional recurrence (LRR), identified by the competing risk regression, were used to establish a predicting nomogram, which was validated in an external cohort (n = 1048). Area under curve (AUC) values of receiver operating characteristic curves were calculated to evaluate discrimination. Risk stratification was conducted using a decision tree analysis based on the cumulative point score of the LRR nomogram, and the effect of PORT was evaluated in each risk group. RESULTS Sex, age, tumor location, tumor grade, and N category were identified as independent risk factors for LRR and added into the nomogram. The AUC values were 0.638 and 0.706 in the training and validation cohorts, respectively. Three risk groups were established. For patients in the intermediate- and high-risk groups, PORT significantly improved the 5-year overall survival by 8.8% and 11.1%, respectively (P < 0.05). Though PORT was significantly associated with reduced LRR in the low-risk group, overall survival was not improved. CONCLUSION The nomogram can effectively estimate the individual risk of LRR, and patients in the intermediate- and high-risk groups are highly recommended to undergo PORT.

Purposes This study aimed to evaluate the role of radiotherapy (RT) and intensity modulated radiation therapy (IMRT) in adjuvant and definitive settings of tracheal-bronchial adenoid cystic carcinoma (TACC) treatment. Materials/methods TACC patients (n = 133) treated with surgery and/or RT curatively in our institution between January 1st, 1984 and December 31st, 2017 were analyzed retrospectively. Results Among the 116 patients undergoing surgery, 50 (43.1 %) achieved complete resections and 66 (56.9 %) had positive surgical margins. For patients with positive margins, overall adjuvant RT was correlated with no significantly improved OS (10-year: 58.0 % vs. 47.9 %; P = 0.340) and a slight LRFS benefit (5-year: 81.9 % vs.75.6 %; P = 0.056), but adjuvant IMRT showed significant superiority in both OS (10-year: 82.9 % vs. 47.9 %; P = 0.031) and LRFS (5-year: 100.0 % vs. 75.6 %; P = 0.001) in comparison with no postoperative RT. Multivariate analysis also identified adjuvant IMRT as a significant favorable factor with OS (HR = 0.186, 95 %CI: 0.039–0.883; P = 0.034). For 17 patients receiving definitive RT, IMRT achieved promising 5-year OS of 88.9 % and LRFS of 64.3 %, yet no significant difference from non-IMRT group was reached (P = 0.447 and 0.706). Different therapies presented no significantly different impact on DMFS, whilst DMFS explained more of the OS variances (P Conclusion IMRT could confer greatly improved OS and LRFS in postoperative setting for TACC patients with positive surgical margins. IMRT was also a good therapeutic option for definitive TACC with promising survival and local control.

Background: Whether thoracic radiotherapy (TRT) could be applied to interstitial lung diseases and lung cancer(ILD-LC) patients safely remains unclear. This retrospective study aims to evaluate the efficacy and safety of definitive TRT in locally advanced non-small cell lung cancer (LA-NSCLC) patients with pre-existing ILD, and to analyze the associated risk factors for radiation induced lung toxicities (RILTs) in the clinical setting. Methods: Patients with histologically confirmed LA-NSCLC and pre-existing ILD treated definitive TRT between 2010 and 2019 were retrospectively reviewed. Patient, tumor, and treatment characteristics were evaluated to determine the risk factors for RILTs. Pre-radiation CT of all patients were reviewed by two radiologists and one pulmonologist and are scored according to Muller’s thin-section CT scoring system for IPF: 0-no discrete honeycombing, with interlobular septal thickening; 1-honeycombing involving 0-5% of the lobe; 2-honeycombing 6-24%; 3-honeycombing 25-49%; 4-honeycombing 50-74%;5-honeycombing >75%. Univariate and multivariate analyses with logistic regression models and cox proportional hazards approach were performed to identify the risk factor(s) of RILTs and overall survival(OS) respectively. Findings: Among 1261 LA-NSCLC patients, 85 were found with pre-existing ILD and enrolled in the analysis. 36·5% of them were scored more than 1 point on CT. 20% patients developed G3+ RILTs within 1 year after the last irradiation, with remarkably 11·8% dying from lung toxicities. And the incidence of symptomatic (G3+) RILTs abruptly dropped to 11·1%(6/54),3·8%(1/26),and 0%(0/19)for patients with CT score≤1, V20 1 and V20≥20% were independently associated with higher risk of G3+ RILTs. The median OS and PFS were 14·0 months and 7·4 month respectively. In the univariate analysis for OS, clinical stage and G3+RILT were evaluated as risk factors while patients in low-risk group, defined as honeycombing score1 and V20≥20% were significantly associated with high incidence of severe lung toxicities, leading to poor survival. However, patients at low risk might benefit from TRT with a considerable overall survival. Funding: None to declare Declaration of Interest: None to declare. Ethical Approval: The study was approved by the institutional review board of National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College (IRB No·NCC2612).

Background: To investigate the survival benefit of concurrent chemoradiotherapy for patients with locally advanced esophageal squamous cell carcinoma during the years of intensity-modulated radiotherapy. Methods: Medical records of 1273 patients with esophageal squamous cell carcinoma who received intensity-modulated radiotherapy from January 2005 to December 2017 in the CAMS were retrospectively reviewed. 683 patients received concurrent chemoradiotherapy, 590 patients received radiotherapy alone. Propensity score matching (PSM) method was used to eliminate baseline differences between the two groups. Survival and toxicity profile were evaluated afterwards. Results: After a median follow-up time of 50.4 months (3.2-157.4 months), both overall survival and progression-free survival of the concurrent chemoradiotherapy group were better than those of the radiotherapy group, either before or after PSM. After PSM, the 1-, 3-, 5-year OS of radiotherapy and concurrent chemoradiotherapy groups were 63.3% vs 72.2%, 31.6% vs 42.2% and 28.5% vs 38.1%, respectively (p=0.003). The 1-year, 3-year and 5-year PFS rates of radiotherapy and concurrent chemoradiotherapy group were 44.3% vs 48.6%, 23.4% vs 31.2% and 15.8% vs 25.2%, respectively (p=0.002). The rates of ≥ grade 3 leukopenia and radiation esophagitis in the concurrent chemoradiotherapy were higher than those in the radiotherapy alone group (pp=0.359). Multivariate logistic regression analysis showed ≥ 70 years old, female, KPS ≤ 70, stage I-II, and patients diagnosed at earlier years (2005-2010) had lower probability of receiving concurrent chemoradiation (p Conclusions: Concurrent chemotherapy can bring survival benefits to patients with locally advanced esophageal squamous cell carcinoma receiving intensity-modulated radiotherapy. For patients who cannot tolerate concurrent chemotherapy, radiation monotherapy is an effective alternative with promising results.

Background The aim of this study was to evaluate the efficacy of postoperative radiotherapy (PORT) in stage pIIIA‐N2 non‐small cell lung cancer (NSCLC) patients with positive surgical margins. Methods Between January 2003 and December 2015, patients who had undergone lobectomy or pneumonectomy plus mediastinal lymph node dissection or systematic sampling in our single institution were retrospectively reviewed. Those with pIIIA‐N2 NSCLC and positive surgical margins were enrolled into the study. The Kaplan‐Meier method was used for survival analysis, and the log‐rank test was used to analyze differences between the groups. Univariate and multivariate analyses using Cox proportional hazards regression models were performed to evaluate potential prognostic factors for OS. Statistically significant difference was set as P, Postoperative radiotherapy (PORT) has been recommended to treat patients with positive surgical margins. However, the existing evidence is controversial and high‐level evidence is lacking. In our study, the PORT group had markedly, but not statistically significant, longer median OS compared with the non‐PORT group in R1 resection patients. OS was significantly longer in the R1 resection patients receiving adjuvant CRT than the surgery alone group.

BACKGROUND: Chemoradiotherapy is the recommended treatment for patients with unresectable locally advanced non-small cell lung cancer (NSCLC). This study aimed to determine the impact of age on the survival outcomes and risk of radiation pneumonitis (RP) in patients with unresectable locally advanced NSCLC. METHODS: The data of patients with unresectable locally advanced NSCLC who were treated with radiotherapy (RT), sequential chemoradiotherapy, or concurrent chemoradiotherapy between January, 2013, and December, 2017, in our institution were retrospectively reviewed and analyzed. Student’s t-test and χ(2) test were used to evaluate the differences between groups divided by optimal cutoff. Survival rates were calculated using the Kaplan-Meier method, and multivariate cox regression was performed to determine the prognostic factors for survival outcomes. RESULTS: A total of 749 patients were included in this analysis. Based on the optimal cutoff, the patients were stratified into two age groups

Introduction: Intensive treatments can often not be administered to elderly patients with esophageal squamous cell carcinoma (ESCC), leading to a poorer prognosis. This multi-center phase II trial aimed to determine the toxicity profile and efficiency of S-1-based simultaneous integrated boost radiotherapy (SIB-RT) followed by consolidation chemotherapy with S-1 in elderly ESCC patients and to evaluate the usefulness of comprehensive geriatric assessment (CGA). Patients and Methods: We prospectively enrolled 46 elderly patients (age ≥ 70 years) with histopathologically proven ESCC. The patients underwent pretreatment CGA followed by SIB-RT (dose, 59.92 Gy/50.4 Gy) in 28 daily fractions administered using intensity-modulated radiotherapy or volumetric-modulated arc therapy. S-1 was orally administered (40-60 mg/m2) concurrently with radiotherapy and 4-8 weeks later, for up to four 3-week cycles at the same dose. Results: The median survival time was 22.6 months. The 1- and 2-year overall survival rates were 80.4 and 47.8%, respectively. The overall response rate was 78.3% (36/46). The incidence of grade 3-4 toxicities was 28% (13/46). The most common grade 3-4 toxicities were radiation esophagitis (5/46, 10.9%), nausea (4/46, 8.7%), anorexia (3/46, 6.5%), and radiation pneumonitis (3/46, 6.5%). There were no grade 5 toxicities. CGA identified that 48.8% of patients were at risk for depression and 65.5% had malnutrition. Conclusion: Concurrent S-1 treatment with SIB-RT followed by 4 cycles of S-1 monotherapy yielded satisfactory tumor response rates and manageable toxicities in selected elderly patients with ESCC. Pretreatment CGA uncovered numerous health problems and allowed the provision of appropriate supportive care. Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT02979691.

Daquan Wang,1,* Jiayun Chen,1,* Xiaodong Zhang,2 Tao Zhang,1 Luhua Wang,1 Qinfu Feng,1 Zongmei Zhou,1 Jianrong Dai,1 Nan Bi1 1Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA*These authors contributed equally to this workCorrespondence: Nan BiDepartment of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 17 Panjiayuannanli, Chaoyang District, Beijing 100021, People’s Republic of ChinaTel +86 10 87788995Email binan_email@163.comBackground: The technique of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) has been widely used in locally advanced non-small cell lung cancer; however, its dosimetric advantages are seldom reported. This study aimed to quantify dosimetric advantages of SIB-VMAT.Methods: Forty patients with stage III non-small cell lung cancer in our hospital were retrospectively included. SIB-VMAT and conventional VMAT (C-VMAT) plans were generated for every patient using the automatic treatment planning system. A reduced dose was delivered to PTV in SIB-VAMT plans compared to C-VMAT plans (50.4Gy vs 60Gy). The prescribed dose was 50.4 Gy in 28 fractions to PTV and 59.92 Gy in 28 fractions to PGTV in SIB-VMAT plans, while 60 Gy in 30 fractions to PTV in C-VMAT plans. Dose-volume metrics of PTV, total lung, heart, esophagus and spinal cord were recorded. The quality score was used to evaluate organs at risk (OAR) protection for two type prescription plans.Results: Conformal coverage of the targets (PGTV/PTV) by 95% of the prescription dose was well achieved in radiation plans. SIB-VMAT plans achieved significantly higher quality score than C-VMAT plans (Mean: 68.15± 13.32 vs 49.15± 13.35, P< 0.001). More plans scored above sixty in SIB-VMAT group compared to C-VMAT group (72.5% vs 20%, P< 0.001). Notable reductions in mean dose, V30, V40 and V50 of total lung were observed in SIB-VMAT plans compared to C-VMAT plans, with median decreased proportions of 6.5%, 8.7%, 19.6% and 32.1%, respectively. Statistically significant decrease in heart V30 and V40 was also achieved in SIB-VMAT plans, with median decreased proportions of 26.1% and 38.8%. SIB-VMAT plans achieved significant reductions in the maximum doses to both esophagus and spinal cord. Patients with CTV/(GTV+GTVnd) ≥ 8.6 showed more notable decrease in total lung V50 (median, 33.6% vs 28.8%, P=0.001) in SIB-VMAT plans compared to those with the ratio being less than 8.6.Conclusion: SIB-VMAT technique could lead to a substantial sparing of normal organs, including lung, heart, esophagus and cord, mainly through reducing high and inter-median dose exposure. Patients with CTV/(GTV+GTVnd) ≥ 8.6 might benefit more from SIB-VMAT.Keywords: lung cancer, simultaneous integrated boost, radiotherapy, automatic planning, organ at risks

Background: The low incidence of primary mediastinal seminomas has precluded the development of clinical trials on mediastinal seminomas. We evaluated the characteristics, treatments, and prognosis of patients with primary mediastinal seminoma. Methods: We retrospectively collected data on the clinicopathologic characteristics, treatments, toxicities, and survival of 27 patients from a single center between 2000 and 2018. Mediastinal lymph node staging for lung cancer and Masaoka staging for thymic neoplasms were used for disease characterization. Survival was assessed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test. Results: The median age was 28 (13-63) years. The most common symptoms were chest pain (29.6%), cough (25.9%), and dyspnea (22.2%). Twenty-four patients showed tumor invasion into adjacent structures. Seven and two patients were diagnosed as having lymph node metastasis and distant metastasis, respectively, whereas 48.1% of patients were diagnosed as having Masaoka stage IIIb disease. Sixteen patients (59.3%) had undergone radiotherapy, whereas 25 (92.6%) had undergone chemotherapy. The most widely used chemotherapy regimens were bleomycin, etoposide, and cisplatin. The median follow-up period was 32.23 (2.7-198.2) months. At 5 and 10 years, the rates of local regional relapse-free survival were 90.9% and 90.9%; overall survival, 100.0% and 80.0%; progression-free survival, 86.4% and 86.4%; distant metastasis-free survival, 95.2% and 95.2%; and cancer-specific survival, 100.0% and 100.0%, respectively. Conclusions: Primary mediastinal seminoma was frequently diagnosed in patients with tumor invasion into adjacent structures. Chemotherapy was the most widely used treatment. The disease was sensitive to chemoradiotherapy, and the prognosis was favorable.

Background The objectives of this study were to determine the objective effective response rate, survival, and safety of radiotherapy combined with gefitinib in patients with locally advanced non-small cell lung cancer (NSCLC) who were unfit for surgery or concurrent chemoradiotherapy. Methods The patients with the locally advanced NSCLC who were unfit to receive surgery or concurrent chemoradiotherapy, received thoracic intensity-modulated radiotherapy (IMRT) combined with gefitinib 250 mg daily. Results 29 patients were enrolled between July 2014 and March 2017. 28 patients was in the analysis. Of the 28 patients, 21 (75.0%) experienced a partial response, 5 (17.9%) had stable disease, and 2 (7.1%) experienced progression of disease. The objective response rate was 75.0%, and the disease control rate was 92.9%. The median follow-up time was 51 months. The disease progression showed in 25 (89.3%) patients, including local progression in 19 (67.9%) and distant metastasis in 16 (57.1%). The median overall survival and progression-free survival time (PFS) were 26 and 11 months, respectively. The 3-, 4-, 5-year survival rates were 39.0, 30.1 and 30.1%, respectively. The 3-, 4-, 5-year PFS rates were 14.3, 9.5 and 9.5%. Two patients developed grade 3 acute adverse events. Seven patients developed grade 2 acute irradiation pneumonitis, and there was no grade 3 acute irradiation pneumonitis. Conclusions For patients with locally advanced NSCLC who are not eligible for surgery or concurrent chemoradiotherapy, IMRT combined with gefitinib can improve the objective effective rate and is generally well-tolerated.

Background : The technique of simultaneous integrated boost volumetric modulated arc therapy (SIB-VMAT) have been widely used in locally advanced non-small cell lung cancer, however, its dosimetric advantages are seldom reported. This study aimed to investigate the dosimetric benefit of SIB-VMAT compared to conventional VMAT plans (C-VMAT). Methods : Forty patients with stage III non-small cell lung cancer in our hospital were randomly selected for the two type prescriptions. SIB-VMAT and C-VMAT plans were generated for each patient with the same optimization parameter by the automatic treatment planning system (TPS). The prescribed dose was 50.4 Gy in 28 fractions to PTV and 59.92 Gy in 28 fractions to PGTV in SIB-VMAT plans, with 60 Gy in 30 fractions to PTV in C-VMAT plans. Dose-volume metrics for the planning target volume, lung, heart, esophagus and spinal cord were recorded. The quality score (S D ) was used to evaluate organ at risks (OARs) protection for two type prescription plans. Results : Conformal coverage of the PGTV/PTV by the 95% of the prescription dose was well achieved in automated plans. SIB-VMAT plans achieved significantly lower S D values than C-VMAT plans (Mean: 0.064±0.106 vs. 0.145±0.181, P=0.001). Obvious reductions in mean dose, V 30 , V 40 and V 50 of total lung were observed in SIB-VMAT plans compared to C-VMAT plans, with median decreased proportions of 6.5%、8.7%、19.6% and 32.1%. Statistically significant decrease in heart V 30 and V 40 were also achieved in SIB-VMAT plans, with median decreased proportions of 26.1% and 38.8%. SIB-VMAT plans achieved significant reductions in the maximum doses to both esophagus and spinal cord. Conclusions : SIB-VMAT technique could lead to a substantial sparing of normal organs, including lung, heart, esophagus and cord, mainly through reducing high and inter-median dose exposure.

Background Baseline lung immune prognostic index (LIPI) was reported as a potential predictive biomarker of immune checkpoint inhibitor treatment and a prognostic biomarker for metastatic non-small cell lung cancer (NSCLC). However, it remains unclear whether LIPI is associated with outcomes in locally advanced NSCLC (LA-NSCLC). Materials/methods Patients with LA-NSCLC receiving radiotherapy between 2000 to 2017 were retrospectively reviewed. Based on pretreatment dNLR and LDH level made up LIPI per previous publications, patients were divided into good group (0 score) and intermediate-poor group (1 or 2 scores). Propensity score matching (PSM) was conducted to balance confounding variables. Results A total of 1079 patients were eligible for analysis. Patients with intermediate-poor pretreatment LIPI had inferior overall survival (OS), progression-free survival (PFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) than those with good LIPI. Multivariate analysis suggested that LIPI was an independent prognostic marker for OS (hazard ratio [HR] = 1.19, 95% CI: 1.02–1.40), PFS (HR = 1.18, 95% CI: 1.02–1.36), and LRRFS (HR = 1.22, 95% CI: 1.05–1.41) in patients with inoperable LA-NSCLC. PSM analysis further verified that intermediate-poor LIPI was an independent prognostic factor for shorter survivals (OS, PFS and LRRFS). Conclusions LIPI is a simple and promising prognostic marker for patients with unresectable LA-NSCLC. Further prospected studies are warranted to validated these findings.

Background There is no consensus on the therapeutic approach to ECOG 2 patients with locally advanced non-small-cell lung cancer (LA-NSCLC), despite the sizable percentage of these patients in clinical practice. This study focused on the efficacy, toxicity and the optimal chemotherapy regimen of CCRT in ECOG 2 patients in a phase III trial. Methods Patients capable of all self-care with bed rest for less than 50% of daytime were classified as ECOG 2 subgroup. A subgroup analysis was performed for ECOG 2 patients recruited in the phase III trial receiving concurrent EP (etoposide + cisplatin)/PC (paclitaxel + carboplatin) chemotherapy with intensity-modulated radiation therapy (IMRT) or three-dimensional conformal external beam radiation therapy (3D-CRT). Results A total of 71 ECOG 2 patients were enrolled into the study. Forty-six (64.8%) patients were treated with IMRT technique. The median overall survival (OS) and progression free survival (PFS) for ECOG 2 patients were 16.4 months and 9 months, respectively. No difference was observed in treatment compliance and toxicities between ECOG 2 patients and ECOG 0–1 patients. Within the ECOG 2 group (31 in the EP arm and 40 in the PC arm), median OS and 3-year OS were 15.7 months and 37.5% for the EP arm, and 16.8 months and 7.5% for the PC arm, respectively (p = 0.243). The incidence of grade ≥ 3 radiation pneumonitis was higher in the PC arm (17.5% vs. 0.0%, p = 0.014) with 5 radiation pneumonitis related deaths, while the incidence of grade 3 esophagitis was numerically higher in the EP arm (25.8% vs. 10.0%, p = 0.078). Conclusions CCRT provided ECOG 2 patients promising outcome with acceptable toxicities. EP might be superior to PC in terms of safety profile in the setting of CCRT for ECOG 2 patients. Prospective randomized studies based on IMRT technique are warranted to validate our findings. Trial registration ClinicalTrials.gov registration number: NCT01494558. (Registered 19 December 2011).

Supplemental material, Supplementary for Role of modern neoadjuvant chemoradiotherapy in locally advanced thymic epithelial neoplasms by Yirui Zhai, Dazhi Chen, Yushun Gao, Zhouguang Hui, Liyan Xue, Zongmei Zhou, Yang Luo, Zefen Xiao and Qinfu Feng in Tumori Journal

Radiation pneumonitis (RP) is one of the major side effects of thoracic radiotherapy. The aim of this study is to build a dose distribution based prediction model, and investigate the correlation of RP incidence and high-order features of dose distribution. A convolution 3D (C3D) neural network was used to construct the prediction model. The C3D network was pre-trained for action recognition. The dose distribution was used as input of the prediction model. With the C3D network, the convolution operation was performed in 3D space. The guided gradient-weighted class activation map (grad-CAM) was utilized to locate the regions of dose distribution which were strongly correlated with grade≥2 and grade

Backgrounds: Chemoradiation therapy (CRT) is the standard care for unresectable locally advanced non-small cell lung cancer (LA-NSCLC). The optimal management of patients with epidermal growth factor receptor gene (EGFR) mutant LA-NSCLC is not determine. Methods: We retrospectively collected data from patients with unresectable stage III lung adenocarcinoma (LAC) harboring EGFR mutations from 2012 to 2018 and categorized their primary treatment as CRT (group 1), combined radiation therapy (RT) and EGFR-tyrosine kinase inhibitors (TKI) with/without chemotherapy (group 2), or EGFR-TKI alone until tumor progression (group 3). Inverse probability of multiple treatment weighting (IPTW) of propensity score was used to compare overall survival (OS) and progression free survival (PFS) between treatments and account for confounding. Findings: EGFR mutations were present in 24.1% of genotyped patients (N=516/2137). Of 440 patients with adequate information, 104, 105, and 231 patients were in groups 1-3. Upon IPTW analysis, adjusted median PFS was 12.4, 26.2 and 16.2 months (log-rank P=0.001) for groups 1-3, and median OS was 51.0, 67.4 and 49.3 months (log-rank P= 0.084), respectively. Comparing to CRT, RT+TKI with/without chemotherapy significantly improved both PFS (adjusted HR [aHR], 0.40; 95% CI, 0.29-0.54; P= 0.001) and OS (aHR, 0.61; 95% CI, 0.38-0.98; P=0.039);TKI alone prolonged PFS (aHR=0.66; 95%CI, 0.50-0.87; P=0.003) but not OS (aHR,0.90; 95% CI, 0.62-1.32; P= 0.595). Similar findings were found in doubly robust IPTW analysis and multivariable Cox regression analysis. Interpretation: First-line use of RT+TKI with/without chemotherapy was associated with the longest PFS and OS compared with CRT or TKI alone in patients with EGFR-mutant unresectable LA-NSCLC. Trial Registration: The study was registered with Clinical Trials.gov, number NCT04304638. Funding Statement: This trial was funded by the National Natural Sciences Foundation Key Program (81572971); CAMS Innovation Fund for Medical Sciences (No. 2017-I2M-1-005), and Sanming Project of Medicine in Shenzhen (No. SZSM201612063) Declaration of Interests: All authors have declared no conflicts of interest. Ethics Approval Statement: The study protocol was approved by the ethics review boards of the Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College. Each participating center obtained regulatory approval per their institutional ethics guidelines.

OBJECTIVES: This study aimed to: (1) assess the prognostic significance of serum tumor markers in locally advanced squamous cell carcinoma in lung (LA-SCCL); (2) generate a nomogram to predict the overall survival (OS) and (3) identify a prognostic stratification to assist the therapeutic decision-making. METHODS: LA-SCCL patients receiving definitive radiotherapy and baseline tumor marker measurement were eligible for this retrospective study. Cox proportional hazards regression was used to determine independent factors associated with various survival indexes and a nomogram was created to estimate the 5-year OS probability for individual patient. The identified prognostic factors were recruited into a recursive partitioning analysis (RPA) for OS to stratify patients with distinct outcome. RESULTS: A total of 224 patients were eligible for analysis. Increased cytokeratin-19 fragment (CYFRA 21-1) was independently associated with inferior OS, progression free survival (PFS) and a borderline decreased local-regional progression free survival (LRPFS). Elevated carcino-embryonic antigen (CEA) served as an unfavorable determinant for OS and increased neuron-specific enolase (NSE) was predictive of poor distant metastasis free survival (DMFS). A nomogram integrating KPS, TNM stage, CEA and CYFRA 21-1 was created, resulting in a c-index of 0.62. RPA identified 4 prognostic classifications, with median OS of 27.6, 19.9, 17.3 and 10.9 months for low, intermediate, high and very-high risk groups, respectively. CONCLUSIONS: Baseline tumor marker panel including CYFRA 21-1, CEA and NSE can be prognostic of outcome for LA-SCCL receiving definitive radiotherapy. The RPA identified four prognostic subgroups, which could assist personalized therapy and clinical trial design in LA-SCCL.

PURPOSE/OBJECTIVE(S) To compare the prognostic predictive power of the 11th Japan Esophageal Society (JES) system with the 8th American Joint Committee on Cancer (AJCC) system in patients with thoracic esophageal squamous cell carcinoma (TESCC), and to estimate the survival benefits of postoperative radiotherapy (PORT) based on substage of the JES system. MATERIALS/METHODS Area under the curve (AUC) values of receiver operating characteristic curve were calculated to evaluate prognostic efficacy. Propensity score matching (PSM) analysis was conducted to balance the two groups (surgery only [S group] or surgery plus postoperative radiotherapy [S+RT group]) across substages of the 11th JES system according to independent prognostic factors for overall survival (OS) identified using the Cox proportional hazards regression. RESULTS A total of 2960 patients were eligible. The 5-year OS AUC for the 8th AJCC system was significantly higher than that for the 11th JES system (0.701 vs. 0.675, P < 0.001). Before PSM, PORT significantly improved 5-year OS rates for patients in stage III and IVA by 9.1% (P < 0.001) and 21.1% (P < 0.001), respectively. After PSM, the 5-year OS rates in stage II, III, and IVA of the S+RT group were significantly higher than those in the S group (70.9%, 39.7%, and 35.1% vs. 57.8%, 27.2%, and 10.3%, respectively; P < 0.001). CONCLUSION The 11th JES system was less capable of predicting prognosis than the 8th AJCC system and patients in stage III of the JES system were highly recommended to undergo PORT.

Purpose/Objective(s) In our previous study, it has been proven that high level of soluble programmed death-ligand 1 (sPD-L1) is considered a predictor of negative clinical outcomes in glioma. However, the expression of sPD-L1 can change dynamically during radiotherapy (RT), and the effect of sPD-L1 has not been thoroughly elucidated. The purpose of this study was to uncover the dynamics of circulating sPD-L1 levels in glioma patients undergoing RT and to investigate the significance of plasma sPD-L1 levels as a biomarker for combining anti-PD-L1 antibody and RT. Materials/Methods Glioma patients treated with RT between October 2019 and September 2020 were prospectively recruited and sPD-L1 levels were measured using enzyme-linked immunosorbent assay (ELISA). Blood samples were obtained before RT (0f), during RT (15 ± 2f) and RT end (30 ± 2f). Flow cytometry were used to address whether circulating sPD-L1 molecules can affect the CD8+ T cells activation and function in the adaptive immune response. Glioma murine model were used to validate whether combine RT and anti-PD-L1 antibody can be a promising therapeutic strategy in gliomas. Results Thirty-two GBM patients treated with RT were included. The proportions of grade I, II, III, and IV gliomas were 6.2%, 28.1%, 21.9%, and 43.8%. RT significantly increased the mean level of sPD-L1 (0f vs. 15 ± 2f: 55.7 ± 19.2 vs.76.7 ± 38.8, P = 0.008; 0f vs. 30 ± 2f: 55.7 ± 19.2 vs.80.94 ± 44.9, P = 0.005). However, there was no significantly difference between during RT (15 ± 2f) and RT end (30 ± 2f). We performed the CD8+ T cells suppression analysis using mice plasma in vitro. The plasma from mice after anti-PD-L1 treatment (the concentration of sPD-L1 could not be detected) didn't show any suppression activity. Instead, the plasma from the mice without anti-PDL1 treatment exhibited the remarkable CD8+ T cell suppression capacity. These results indicated that the sPD-L1 can play an important role in T cell suppression. Furthermore, the glioma murine model indicated that the combination of irradiate (IR) and anti-PD-L1 significantly reduced tumor growth than either IR or anti-PD-L1 antibody monotherapy (anti-PD-L1 vs. IR plus anti-PD-L1: 789.67 ± 55.86 mm3 vs. 292.16 ± 102.98 mm3 on day 31, P Conclusion This study reported that sPD-L1 might be a potential biomarker in glioma patients receiving RT. This finding means that compensation for the potential sequestration of antibodies needs to be considered in the optimization of PD-L1 blockade therapies. Because not all administered anti-PD-L1 immunotherapeutic antibodies may reach the surface of tumor cells, with a potentially appreciable proportion being sequestered by sPD-L1 within the circulation. The elevated level of sPD-L1 after RT suggested that the strategy of a combination of immune checkpoint inhibitors and RT might be promising for glioma patients. Author Disclosure X. Ding: None. Z. Zhou: None. Z. Ge: None. Y. Guo: None. Y. Chen: None. S. Nie: None. J. Yu: None. M. Hu: None.

Purpose/objective(s) To investigate the timing and pattern of recurrence in stage IIIA-N2 non-small cell lung cancer (NSCLC) patients after complete resection and adjuvant chemotherapy. Materials/methods The study cohort included pathologically confirmed stage IIIA-N2 NSCLC patients treated with complete resection and adjuvant chemotherapy from 2003 to 2015 in our single institution. Recurrence was categorized as local-regional recurrence (LRR), distant metastasis (DM) and both LRR and DM. The risk distribution was assessed by using clinical and pathological factors. The hazard rate function and competing risk analysis were used to evaluate the recurrence dynamics. The Gray's test was employed to estimate the cumulative recurrence rates and compare the differences between groups. Results Among 854 patients, 61.9% had multiple station N2 involvement. The 1, 3 and 5-year cumulative incidence rates of recurrence was 16.85%, 50.74% and 67.37%, respectively. Of the 510 patients who experienced recurrence, 95 (18.6%) experienced LRR, 285 (55.9%) experienced DM, whereas 130 (25.5%) had both LRR and DM. The hazard rate function for overall recurrence revealed a continuous increase between 0-18 months after surgery, consistent high level during 8-48 months and marked decline thereafter. And the DM displayed a hazard rate curve similar to that of overall recurrence. However, a double-peaked pattern of hazard rate was present in LRR and both LRR and DM. What's more, the peak recurrence frequency of DM differed by organs. A comparison of clinical and pathological factors revealed that patients with lower pT stage, single pN2 station and postoperative radiotherapy had a lower recurrence risk but similar pattern of recurrence. Conclusion 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.

Importance The role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non–small cell lung cancer (NSCLC). Objective To evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy. Design, Setting, and Participants The PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020. Interventions Patients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy. Main Outcomes and Measures The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence–free survival (LRFS), distant metastasis–free survival, and toxic effects. Results In total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09;P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rankP = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02;P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97;P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00;P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30;P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray testP = .04). No radiotherapy-related grade 4 or 5 adverse event was observed. Conclusions and Relevance In this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed. Trial Registration ClinicalTrials.gov Identifier:NCT00880971

Background Systematic inflammation has been thought to play a crucial role in tumorigenesis and metastasis. This study is aimed to evaluate the prognostic value of time-series behavior of systematic inflammation-immune status before and after definitive chemoradiotherapy (dCRT) in patients with locally advanced non-small cell lung cancer (LA-NSCLC). Methods The relation between systematic inflammation-immune score (SIS, defined as pretreatment peripheral platelet count × neutrophil count / lymphocyte count) and prognosis was tested in a retrospective study of 386 consecutive LA-NSCLC patients (Group A) with pretreatment SIS and 161 patients (Group B) with SIS before and one month after dCRT. Results SIS of 1400 × 109 was found to be an optimal cutoff point to stratify the patients into high (>1400 × 109) and low (≤1400 × 109) SIS groups. Univariate and multivariate analyses revealed that the SIS, whether before or after dCRT, was an independent predictor for overall survival (OS), progress-free survival (PFS) and distant metastasis-free survival (DMFS). High SIS (>1400 × 109) was shown to predict poor 3-year OS (p=0.006, hazard ratio [HR]=2.427), PFS (p=0.001, HR=2.442) and DMFS (p=0.015, HR=2.119). However, SIS was not related with Local regional recurrence-free survival either in Group A (p=0.346) or Group B (p=0.486). Further, the area under the receiver operating characteristic curve of the SIS for OS was higher than neutrophil count / lymphocyte count ratio, platelet count / lymphocyte count ratio and other conventional clinic-pathological indices. Conclusions The SIS is a stable and more sensitive survival predictor than other inflammation‑based factors and conventional clinical indices, which may aid in more accurately stratifying patients for risk assessment and treatment decision.