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Purpose We initially aimed to ascertain the application value of inflammatory indexes in predicting severe acute radiation pneumonitis (SARP). Furthermore, a novel nomogram and risk classification system integrating clinicopathologic, dosimetric, and biological parameters were built to provide individualized risk assessment and accurate prediction of SARP in patients with esophageal cancer who received radiation therapy. Methods and Materials All data were retrospectively collected from 416 esophageal cancer patients in 2 participating institutes. A novel nomogram was constructed that forecasted SARP based on logistic regression analyses. The concordance index, calibration curves, and decision curve analyses were used by both internal and external validation to demonstrate discriminatory and predictive capacity. Moreover, a corresponding risk classification system was generated by recursive partitioning analysis. Results The Subjective Global Assessment score, pulmonary fibrosis score, planning target volume/total lung volume, mean lung dose, and ratio of change regarding systemic immune inflammation index at 4 weeks in the course of treatment were independent predictors of SARP and finally incorporated into our nomogram. The concordance index of nomogram for SARP prediction was 0.852, which showed superior discriminatory power (range, 0.604-0.712). Calibration curves indicated favorable consistency between the nomogram prediction and the actual outcomes. Decision curve analyses exhibited satisfactory clinical utility. A risk classification system was established to perfectly divide patients into 3 different risk groups, which were low-risk group (6.1%, score 0-158), intermediate-risk group (37.3%, score 159-280), and high-risk group (78.9%, score >280). Conclusions The Subjective Global Assessment score, pulmonary fibrosis score, planning target volume/total lung volume, mean lung dose, and ratio of change regarding systemic immune inflammation index at 4 weeks were potential valuable markers in predicting SARP. The developed nomogram and corresponding risk classification system with superior prediction ability for SARP could assist in patient counseling and provide guidance when making treatment decisions.

Objectives We aimed to identify the risk factors and provide a nomogram for the prediction of radiotherapy-related esophageal fistula in patients with esophageal cancer (EC) using a case-control study. Patients and methods Patients with esophageal fistula who received radiotherapy or chemoradiotherapy between 2003 and 2017 were retrospectively collected in two institutions. In the training cohort (TC), clinical, pathologic, and serum data of 136 patients (cases) who developed esophageal fistula during or after radiotherapy were enrolled and compared with 272 controls (1:2 matched with the diagnosis time of EC, sex, marriage, and race). After the univariable and multivariable logistic regression analyses, the independent risk factors were identified and incorporated into a nomogram. Then the nomogram for the risk prediction was externally validated in the validation cohort (VC; 47 cases and 94 controls) using bootstrap resampling. Results Multivariable analyses demonstrated that ECOG PS, BMI, T4, N2/3 and re-radiotherapy were independent factors for esophageal fistula. Then a nomogram was constructed with the C-index of 0.805 (95% CI, 0.762–0.848) for predicting the risk of developing esophageal fistula in EC patients receiving radiotherapy. Importantly, the C-index maintained 0.764 (95% CI, 0.683–0.845) after the external validation. Conclusions We created and externally validated the first risk nomogram of esophageal fistula associated with radiotherapy. This will aid individual risk stratification of patients with EC developing esophageal fistula.

Aim: To compare the efficacy and toxicity of local therapy plus chemotherapy versus chemotherapy in non-small-cell lung cancer (NSCLC) patients with oligometastases after surgery. Patients & methods: A total of 152 patients with oligometastases after surgery were enrolled. Data of patient survival, treatment response and toxicities were compared between the groups receiving local ablative therapy plus chemotherapy and chemotherapy alone. Results: Compared with chemotherapy, the combination treatment conferred better progression-free survival, objective response rate and disease control rate (10 vs 7 months; 66.7 vs 31.9%; 94.3 vs 80.9%, respectively), but with more grade ≥3 adverse events. Besides, the overall survival was not significantly different (19 vs 20 months). Conclusion: The addition of local therapy to chemotherapy improved progression-free survival, objective response rate and disease control rate, but not overall survival in postoperative oligometastatic non-small-cell lung cancer.

Aim: To dynamically investigate the prognostic value of albumin-to-alkaline phosphatase ratio (AAPR) in limited stage small-cell lung cancer. Materials & methods: The AAPR within 1 week before and after chemoradiation therapy (pre- and post-AAPR) was collected and analyzed. Results: Patients with low pre- or post-AAPR had shorter overall survival and progression-free survival than the high groups (p-values all

Background: Bevacizumab combined with chemotherapy is still one of the standard options for treatment of advanced non-small cell lung cancer (NSCLC) patients without driver mutations. Serum inflammatory factors, representing the systemic immune status, are shown to have complicated relationships with tumor angiogenesis, and proved to be associated with survival of advanced NSCLC patients. However, the information from the baseline factors is relatively limited, which cannot reflect the dynamic changes of systemic immune status during bevacizumab treatment. We, thus, attempted to evaluate longitudinal kinetics of systemic inflammatory factors during treatment of bevacizumab and to explore their predictive role in treatment response and patient outcomes in advanced NSCLC. Method: Systemic inflammatory factors (neutrophil/lymphocyte (NLR), platelet/lymphocyte (PLR), neutrophil×platelet/lymphocyte (SII) and lymphocyte/monocyte (LMR)) and clinical variables were collected and analyzed from 161 advanced NSCLC patients treated with bevacizumab. Mixed effect regression models were first performed for longitudinal analysis of the changes of serum inflammatory factors during bevacizumab treatment. Then, univariate and multivariate Cox models were used for overall survival (OS) and progression free survival (PFS) analyses to determine the independent prognostic factors. Results: In the first 6 cycles of bevacizumab treatment, patients with complete response/partial response (CR/PR) had a -0.11, -0.066, -0.15, and 0.073 change every 2 cycles in transformed NLR (95%CI: -0.19--0.03, p=0.008), PLR (95%CI: -0.12--0.013, p=0.015), SII (95%CI: -0.23--0.05, p

4016 Background: 70% of esophageal carcinoma are unresectable at diagnosis. Despite active clinical research on the treatment of esophageal squamous cell carcinoma (ESCC), the long-term survival rate of advanced patients is still very low, with a 5-year survival rate of 30%-40%. A prospective, randomized-controlled, double-blinded, multicenter, and phase III study (NXCEL1311) was designed to investigate the efficacy and safety of nimotuzumab (anti-EGFR humanized monoclonal antibody;abbreviate,Nimo) plus concurrent chemo-radiotherapy compared with placebo plus chemo-radiotherapy in unresectable locally advanced ESCC. Methods: Unresectable locally advanced ESCC patients were randomized (1:1) to receive Nimo (400 mg, qw) or placebo in combination with concurrent chemo-radiotherapy (paclitaxel+ cisplatin+3DCRT/IMRT) for seven weeks. Patients were followed for five years.The primary endpoints were OS, and the secondary endpoints included ORR, DCR, PFS. Results: 200 patients were assigned to the Nimo group (n = 99) or placebo group (n = 101). An interim analysis was conducted for short term efficacy, i.e secondary endpoints (ORR, DCR) and safety, after completing the 6 months follow-up. The OS events are not enough for analysis. The two groups were comparable on baseline characteristics. Eighty patients in the Nimo group and eighty-two patients in the placebo group were evaluable. The ORR of the Nimo group (75/80, 93.8%) was significantly higher than the placebo group (59/82, 72.0%;Chi-square test, p < 0.001). Twenty-six patients in the Nimo group reached the complete response (CR), and ten placebo group patients were CR. The CR rate in the Nimo group was significantly higher than placebo group (32.5% vs.12.2%, p = 0.002). The DCR of the Nimo group and placebo group were 98.8% (79/80) and 91.5% (75/82), respectively (p = 0.064). Single factor logistic aggression analysis showed that age, sex, target lesion number, and BMI did not affect ORR, CR, and DCR (p > 0.05). Multiple factor correction analysis showed the difference of CR, ORR and DCR between two groups is 20% (95%CI 6.0%̃40.2%), 30% (95%CI 10.6%̃52.1%) and 10% (95%CI -5.2%̃31.1%). The incidence of grade 3-5 drug-related AEs was 11.1%vs.10.9% (p > 0.05). Common drug-related AEs in patients with Nimo plus chemo-radiotherapy treatment were leucopenia, neutrophilic granulocytopenia, thrombocytopenia, hemoglobin, bone marrow inhibition, nutritional anemia, and radioactive inflammation. Conclusions: This interim analysis showed that nimotuzumab in combination with chemo-radiotherapy is safe and can increase the CRR and ORR of the treated patients. The OS needs to be followed and finally analyzed. Clinical trial information: 02409186.

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and thoracic radiotherapy (TRT) has shown significant clinical activity in patients with non-small cell lung cancer (NSCLC). However, the currently available data on adverse events (AEs) were derived from a small subset of patients included in prospective clinical trials or retrospective studies. Thus, we conducted this systematic review to determine the AEs associated with this combination treatment.MethodsAn electronic literature search was performed in databases and conference proceedings of prospective clinical trials assessing the combination of ICIs and TRT for patients with NSCLC. The systematic analysis was conducted to determine the profile and incidence of AEs of combination treatment. We further performed the comparison of AEs between programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors, and sequential and concurrent administration of ICIs and TRT to help identify high risk patients. The systematic analyses were conducted with the Review Manager (version 5.3; The Cochrane Collaboration, Oxford, United Kingdom) and Stata version 12.0 (StataCorp, College Station, TX, USA) software.ResultsEleven clinical trials involving 1,113 patients with NSCLC were eligible for analysis. The incidence of all-grade AEs was 95.5%; that of high-grade AEs (grade ≥3) was 30.2%. The most frequent all-grade AE was fatigue (49.7%), while pneumonitis was the most common high-grade AE (3.8%) and grade 5 AE (0.6%). Notably, the toxicity profiles of PD-1 and PD-L1 inhibitors were similar. Concurrent treatment was associated with a higher incidence of higher-grade AEs (41.6% vs 24.8%, P=0.17) and pneumonitis (7.1% vs 3.9%, P=0.14) compared to sequential treatment, but no significant difference was observed.ConclusionMost AEs of this combination treatment are tolerable; as the most common high-grade AE, pneumonitis deserves the utmost attention of physicians. The toxicity profiles of patients receiving PD-1 or PD-L1 were similar, and no significant difference was observed between concurrent and sequential treatment.

Background Radiation-induced pneumonitis (RP) is a non-negligible and sometimes life-threatening complication among patients with thoracic radiation. We initially aimed to ascertain the predictive value of acute radiation-induced esophagitis (SARE, grade ≥ 2) to symptomatic RP (SRP, grade ≥ 2) among thoracic cancer patients receiving radiotherapy. Based on that, we established a novel nomogram model to provide individualized risk assessment for SRP. Methods Thoracic cancer patients who were treated with thoracic radiation from Jan 2018 to Jan 2019 in Shandong Cancer Hospital and Institute were enrolled prospectively. All patients were followed up during and after radiotherapy (RT) to observe the development of esophagitis as well as pneumonitis. Variables were analyzed by univariate and multivariate analysis using the logistic regression model, and a nomogram model was established to predict SRP by “R” version 3.6.0. Results A total of 123 patients were enrolled (64 esophageal cancer, 57 lung cancer and 2 mediastinal cancer) in this study prospectively. RP grades of 0, 1, 2, 3, 4 and 5 occurred in 29, 57, 31, 0, 3 and 3 patients, respectively. SRP appeared in 37 patients (30.1%). In univariate analysis, SARE was shown to be a significant predictive factor for SRP (P P Conclusions As an early index that can reflect the tissue’s radiosensitivity visually, SARE can be used as a predictor for SRP in patients receiving thoracic radiation. And the nomogram containing SARE may be fully applied in future’s clinical work.

Introduction The immune status of the tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status, and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients. Methods In this study, 100 patients who were diagnosed as having inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A five immune features-based signature was then constructed using the nested repeat 10-fold cross validation with least absolute shrinkage and selection operator (LASSO) Cox regression model. Nomograms were then established for predicting prognosis. Results The immune signature combining five immuno-features was significantly associated with overall survival (OS) and progression-free survival (PFS) (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of -0.05 stratified patients into two groups with 5-year OS rates of 39.8 and 8.8%, and 2-year PFS rates of 22.2 and 5.5% for the high- and low-immune signature groups, respectively. Integrating immune signature, we proposed predictive nomograms that were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that the immune signature plays a significant role in improving the prognostic value. Conclusion Multiple immune features-based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients and complemented the prognostic value of the TNM staging system.

Butuo Li,1 Chao Jiang,2 Ruiqing Wang,3 Bing Zou,1 Peng Xie,1 Wanlong Li,1 Xindong Sun,1 Jinming Yu,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250017, Shandong Province, People’s Republic of China; 2Department of Otorhinolaryngology, Head and Neck Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province 250021, People’s Republic of China; 3Department of Breast Surgery, Linyi People’s Hospital, Linyi 276000, Shandong Province, People’s Republic of ChinaCorrespondence: Linlin Wang Tel +86-531-67626142Fax +86-531-67626141Email wanglinlinatjn@163.comPurpose: Small-cell lung cancer (SCLC) is known as the characteristics of high invasion, rapid progression, and poor prognosis. Therefore, identification of patients with high risk of progression and death is critical to improve the survival of patients with extensive-stage SCLC (ES-SCLC). This study was designed to determine the prognostic importance of the albumin-to-alkaline phosphatase ratio (AAPR) in the survival of patients with ES-SCLC and to develop a nomogram based on AAPR dynamics for ES-SCLC prognosis.Patients and Methods: Characteristics were reviewed from 300 patients with ES-SCLC. Training and validation cohorts included 200 and 100 patients, respectively. We applied univariate and multivariate Cox models to assess the prognostic value of AAPR for ES-SCLC. The nomogram for progression-free survival (PFS) and overall survival (OS) of ES-SCLC patients was developed based on the multivariate survival analysis of the training cohort. External validation of the established nomogram was performed using the validation cohort.Results: N3 stage, thoracic radiotherapy, and post-AAPR were the independent factors identified for PFS. T stage, thoracic radiotherapy, and high post-AAPR were the independent risk factors identified for death. The prognostic nomogram was established by integrating the independent significant factors for PFS and OS in the training cohort with the c-indices of 0.675 and 0.662, respectively, and validated in the validation cohort. The nomogram had superior prognosis prediction ability than did TNM stage. Decision curve analysis (DCA) also indicated clinical net benefits from the nomogram.Conclusion: AAPR was valuable for prognosis prediction in patients with ES-SCLC and was recommended to be dynamically evaluated to guide patient treatment. Additionally, the nomogram covering post-AAPR accurately predicted individual survival probability.Keywords: extensive-stage small-cell lung cancer; ES-SCLC, albumin-to-alkaline phosphatase ratio; AAPR, dynamic, nomogram, prognosis prediction

Platinum-based chemotherapy is recommended as the standard treatment for metastatic esophageal cancer (EC) patients; however, the outcome is poor. Oligometastasis is less aggressive and has limited growth potential. However, the prognostic factors for EC patients with oligometastases was largely unknown. Thus, we intend to determine the prognostic factors, and develop and validate nomograms for prediction of survival for EC patients with oligometastases. In this study, characteristics of 273 oligometastatic EC patients were analyzed using univariate and multivariate Cox models to determine the independent prognostic factors for progression-free survival (PFS) and overall survival (OS). The result showed that history of alcohol consumption, longer tumor, no local radiotherapy for EC, and no local treatment for metastases were independent factors for PFS. Sex, esophageal fistula, number of metastatic organs, and local radiotherapy for EC were independent prognostic factors for OS. On the basis of Cox models, the respective nomogram for prediction of PFS and OS was established with the corrected concordance index of 0.739 and 0.696 after internal cross-validation. In conclusion, local treatment for metastases and local radiotherapy for EC were demonstrated to be beneficial for oligometastatic EC patients, and the validated nomograms are valuable in prognosis prediction and could guide individualized management for these patients.

To assess tumor cell proliferation and repopulation during fractionated radiotherapy and investigate the spatial concordance of cell proliferation and repopulation according to the uptake of 3′-[18F]fluoro-3′-deoxythymidine ([18F]FLT). Mice bearing A549 xenograft tumors were assigned to five irradiated groups, including 3 fraction (f)/6 days (d), 6f/12d, 9f/18d, 12f/24d, and 18f/36d with 2 Gy/f irradiations performed every other day and one non-irradiated group. Serial [18F]FLT positron emission tomography (PET) scans were performed at different time points as the groups finished the radiotherapy. The maximum of standard uptake values (SUVmax) were measured to confirm the likely time of tumor repopulation. A layer-by-layer comparison between SUVmax of PET images and Ki-67 LI of pathology images, including the thresholds at which maximum overlap occurred between FLT-segmented areas and cell proliferation areas were conducted to evaluate the spatial correlation. The SUVmax decreased in the 3f/6d group (P = 0.000) compared to the non-irradiated group, increased in the 6f/12d group and then gradually reduced with prolonged treatment. Proliferation changes in 6f/12d group on pathology images were also confirmed. Significant correlations were found between the SUVmax and Ki-67 LI in each in vitro tumor of cell proliferation group and accelerated repopulation group (both of the P

Extramedullary hematopoiesis (EMH) usually occurs in hematological disease, but more rarely develops in cases of malignant solid tumors. Due to its features on computed tomography (CT) and magnetic resonance imaging (MRI) that are atypical, EMH in tumor patients might easily be misdiagnosed as metastasis leading to the improper TNM staging and inappropriate therapy. Here, we reported the first case of pleural EMH occurring in a patient with esophageal carcinoma whose pleural lesion was first diagnosed as metastasis and confirmed EMH after the needle biopsy. In addition, a retrospective review was conducted by analyzing patients presented with EMH with malignant solid tumors from PubMed and Medline databases. A total of 42 solid tumor patients with EMH were enrolled, and breast cancer was the most common (n=13, 31.0%), followed by renal carcinoma (n=7, 16.7%) and lung cancer (n=6, 14.3%). A wide variety of body sites may be affected by EMH in malignant solid tumor patients, of which the lymph nodes (n=8, 19.0%) and liver (n=7, 16.7%) were the most common, followed by the kidney (n=6, 14.3%). All patients were diagnosed with EMH by excision, biopsy, or autopsy. Treatment strategies for EMH included surgery (n=25, 59.5%), hydroxyurea (n=1, 2.4%), and blood transfusions (n=2, 4.8%); a further 14 patients (33.3%) were subjected to clinical observation without intervention. Of the patients for whom outcome was reported, 10 patients maintained a good performance status (23.8%) and a further six patients died from the malignant tumor. This was the first study to summarize the presentations of EMH in malignant solid tumors, and our findings might provide some useful guidance for clinical practice, especially for treating patients harboring nonresponse lesions during the antitumor treatment.

// Qiang Wen 1, 2 , Xue Meng 1, 2 , Peng Xie 1, 2 , Shijiang Wang 1, 2 , Xindong Sun 1, 2 and Jinming Yu 1, 2 1 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong University, Jinan, 250117, China 2 Shandong Academy of Medical Sciences, Jinan, 250117, China Correspondence to: Jinming Yu, email: sdyujinming@163.com Keywords: small cell lung cancer, refractory, platinum-sensitivity status, survival, chemoradiotherapy Received: January 04, 2017 Accepted: June 27, 2017 Published: July 07, 2017 ABSTRACT In this retrospective study, we analyzed the association of clinicopathological factors and therapeutic plans with platinum-sensitivity status and survival of limited-stage small cell lung cancer (LS-SCLC) patients. We enrolled 452 LS-SCLC patients with 279 platinum sensitive and 173 platinum refractory patients. The low serum neuro-specific enolase levels (NSE; p = 0.011), neutrophil-to-lymphocyte ratios (NLR; p = 0.013) and higher objective response rates ( p = 0.003) were associated with sensitive group but not the refractory group. Multivariate analysis showed that treatment modality (HR = 0.267, p < 0.001), serum lactate dehydrogenase (LDH; HR = 1.894, p = 0.016), NLR (HR = 2.043, p = 0.043) and platinum-sensitivity status (HR = 0.561, p = 0.036) were independent prognostic factors for survival. We further showed that the numbers of chemotherapy cycles and response to first-line therapy were independent prognostic factors for refractory patients only. Our study demonstrates that platinum-sensitivity status is of prognostic importance, as it is strongly associated with survival in LS-SCLC patients.

// Bingjie Fan 1 , Pingping Fan 1, 2, 3 , Li Kong 1, 2, 3 , Xindong Sun 1, 2, 3 , Shuqiang Zhao 1, 2, 4 , Xiaorong Sun 1, 2, 4 , Zheng Fu 1, 2, 4 , Jinsong Zheng 1, 2, 4 , Li Ma 1, 2, 4 , Shijiang Wang 1, 2, 3 , Man Hu 1, 2, 3 and Jinming Yu 1, 2, 3 1 Shandong Cancer Hospital Affiliated to Shandong University, Jinan, China 2 Shandong Academy of Medical Sciences, Jinan, China 3 Departments of Radiation Oncology and Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, China 4 Departments of Nuclear Medicine, Shandong Cancer Hospital and Institute, Jinan, China Correspondence to: Man Hu, email: hu5770@sina.com Jinming Yu, email: sdyujinming@163.com Keywords: esophageal squamous cell carcinoma, radiotherapy, FDG PET/CT, concurrent chemoradiotherapy, local failure Received: October 15, 2016 Accepted: January 04, 2017 Published: February 22, 2017 ABSTRACT Esophageal squamous cell carcinoma (ESCC) patients are at risk for local failure (LF) following treatment. Predicting tumor regions at high risk for local failure before radiotherapy may increase treatment efficacy by permitting an escalated radiation dose specifically to those regions critical for tumor control. Forty-one patients with non-resectable locally advanced ESCC underwent 18 F-deoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging before concurrent chemoradiotherapy (CCRT). After CCRT, a second (failure) FDG PET/CT was performed in cases of relapse. Failure FDG PET/CT scans were fused to pre-treatment scans to identify tumor regions at high risk for LF. Within a median follow-up time of 26 months, 20 patients (48.8%) had LF. In 19 patients, the failure occurred within a pre-treatment high FDG uptake region; the failure occurred outside these regions in only one patient. Pre-treatment metabolic tumor volume (MTV) was independently associated with LF ( P

Objectives: To compare treatment plans of intensity modulated radiotherapy (IMRT), volumetric modulated arc radiotherapy (VMAT), and helical tomotherapy (HT) with simultaneous integrated boost (SIB) technique for esophageal cancer (EC) of different locations using dosimetry and radiobiology.Methods: Forty EC patients were planned for IMRT, VMAT, and HT plans, including 10 cases located in the cervix, upper, middle, and lower thorax, respectively. Dose-volume metrics, conformity index (CI), homogeneity index (HI), tumor control probability (TCP), and normal tissue complication probability (NTCP) were analyzed to evaluate treatment plans.Results: HT showed significant improvement over IMRT and VMAT in terms of CI (p = 0.007), HI (p < 0.001), and TCP (p < 0.001) in cervical EC. IMRT yielded more superior CI, HI and TCP compared with VMAT and HT in upper and middle thoracic EC (all p < 0.05). Additionally, V30 (27.72 ± 8.67%), mean dose (1801.47 ± 989.58cGy), and NTCP (Niemierko model: 0.44 ± 0.55%; Lyman-Kutcher-Burman model: 0.61 ± 0.59%) of heart in IMRT were sharply reduced than VMAT and HT in middle thoracic EC. For lower thoracic EC, the three techniques offered similar CI and HI (all p > 0.05). But VMAT dramatically lowered liver V30 (9.97 ± 2.84%), and reduced NTCP of lungs (Niemierko model: 0.47 ± 0.48%; Lyman-Kutcher-Burman model: 1.41 ± 1.07%) and liver (Niemierko model: 0.10 ± 0.08%; Lyman-Kutcher-Burman model: 0.17 ± 0.17%).Conclusions: HT was a good option for cervical EC with complex target coverage but little lungs and heart involvement as it achieved superior dose conformity and uniformity. Due to potentially improving tumor control and reducing heart dose with acceptable lungs sparing, IMRT was a preferred choice for upper and middle thoracic EC with large lungs involvement. VMAT could ameliorate therapeutic ratio and lower lungs and liver toxicity, which was beneficial for lower thoracic EC with little thoracic involvement but being closer to heart and liver. Individually choosing optimal technique for EC in different location will be warranted.

Objectives Cisplatin-based chemotherapy as an adjuvant therapy for resected non-small cell lung cancer (NSCLC) has reached its plateau, and it is limited by a high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected NSCLC harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as an adjuvant therapy for targeted patients. Materials and methods Studies were identified via electronic search. The pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for the meta-analysis. Results There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. The results showed that adjuvant treatment with EGFR-TKIs can prolong both the OS and DFS when compared to treatment without TKIs as an adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I2 = 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P Conclusion The addition of EGFR-TKIs to adjuvant chemotherapy can prolong the OS and PFS for resected NSCLC. Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completely resected patients with EGFR mutation-positive NSCLC. Statement of significance The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. This study demonstrates that EGFR-TKIs as an adjuvant therapy could prolong the DFS and potentially prolong the OS in postoperative patients. Therefore, this therapy paves the way for EGFR-TKIs to be an adjuvant treatment for NSCLC.

OBJECTIVE Inflammation plays critical roles in tumor growth and progression, and can be adversely affected by chemotherapy and radiotherapy. However, there have been few studies on the prognostic value of delta (Δ) inflammatory biomarkers before and after chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS In this study, pre/post-treatment and Δ inflammatory biomarkers of 370 patients who were diagnosed as having inoperable LA-NSCLC in Shandong Cancer Hospital between January 2005 and January 2016 were analyzed. Nomograms were then established for predicting prognosis. RESULTS Median overall survival (OS) and progression free survival (PFS) for all patients were 28.1 (range 1.9-129.0) months and 11.1 (range 1.7-58.7) months, respectively. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) significantly increased and the lymphocyte-to-monocyte ratio (LMR) significantly decreased during the concurrent chemoradiotherapy course (P

Differences in gross target volume (GTV) and central point positions among moving lung cancer models constructed by CT scanning at different frequencies were compared, in order to explore the effect of different respiratory frequencies on the GTV constructions in moving lung tumors. Eight models in different shapes and sizes were established to stimulate lung tumors. The three-dimensional computed tomography (3DCT) and four-dimensional computed tomography (4DCT) scanning were performed at 10, 15 and 20 times/min in different models. Differences in GTV volumes and central point positions at different motion frequencies were compared by means of GTV3Ds (GTV3D-10, GTV3D-15, GTV3D-20) and IGTV4Ds (IGTV4D-10, IGTV4D-15, IGTV4D-20). Volumes of GTV3D-10, GTV3D-15, GTV3D-20 were 12.41±14.26, 10.38±11.18 and 12.50±15.23 cm3 respectively (P=0.687). Central point coordinates in the x-axis direction were −8.16±96.21, −8.57±96.08 and −8.56±95.73 respectively (P=0.968). Central point coordinates in the y-axis direction were 108.22±25.03, 110.41±22.47 and 109.04±24.24 (P=0.028). Central point coordinates in the z-axis direction were 65.19±13.68, 65.43±13.40 and 65.38±13.17 (P=0.902). The difference was significant in the y-axis direction (P=0.028). Volumes of IGTV4D-10, IGTV4D-15, IGTV4D-20 were 17.78±19.42, 17.43±19.56 and 17.44±18.80 cm3 (P=0.417). Central point coordinates in the x-axis direction were −7.73±95.93, −7.86±95.56 and −7.92±95.14 (P=0.325). Central point coordinates in the y-axis direction were 109.41±24.54, 109.60±24.13 and 109.16±24.28 (P=0.525). Central point coordinates in the z-axis direction were 65.52±13.31, 65.59±13.39 and 65.51±13.34 (P=0.093). However, the central point position of GTV in the head and foot direction by 3DCT scanning was severely affected by the respiratory frequency.

4553 Background: We aimed to propose a risk model based on MM-Atten-CNN for predicting esophageal fistula in patients with esophageal cancer (EC) from computerized tomography (CT) -based radiomics. Methods: EC patients who didn’t received esophageal surgery between July 2014 and August 2019 were collected. Of these, 186 patients (cases) who developed esophageal fistula were enrolled and compared with 372 controls (1:2 matched with the diagnosis time of EC, sex, marriage, and race). All 558 patients were divided into training set (n = 390) and validation set (n = 168) randomly. The MM-Atten-CNN risk model was trained over 2D slices from nine views of planes, where there were three patches of contextual CT, segmented tumor and neighbouring information in each view. In the training set (130 cases and 260 controls), data augmentation was performed including pixel shifting [-10, -5, +5, +10] and rotation [-10, +10]. In total, there were (130+260) *16*2 = 12480 subjects used for training. Finally, the risk model was validated in the validation set (56 cases and 112 controls) and measured by accuracy (acc), sensitivity (sen), and specificity (spe). Results: The developed risk model achieved (acc, sen, spe) of (0.839, 0.807, 0.926), which were more predictive for the occurrence of esophageal fistula when compared to CNN models using single coronal view (acc 0.763, sen 0.581, spe 0.837), multi-view 2D contextual CT slices (acc 0.779, sen 0.656, spe 0.896), and 3D CNN using contextual CT volumes (acc 0.781, sen 0.689, spe 0.852). Conclusions: MM-Atten-CNN CT-based model improved the performance of esophageal fistula risk prediction, which has the potential to assist individualized stratification and treatment planning in EC patients.

e21066 Background: The immune status of tumor microenvironment is extremely complex. One single immune feature cannot reflect the integral immune status and its prognostic value was limited. We postulated that the immune signature based on multiple immuno-features could markedly improve the prediction of post-chemoradiotherapeutic survival in inoperable locally advanced non-small-cell lung cancer (LA-NSCLC) patients. Methods: In this study, 100 patients who were diagnosed as inoperable LA-NSCLC between January 2005 and January 2016 were analyzed. A 5-immune feature-based signature was then constructed using the nested repeat 10-fold cross validation with LASSO Cox regression model. Nomograms were then established for predicting prognosis. Results: Immune signature combining 5 immuno-features were significantly associated with OS and PFS (P = 0.002 and P = 0.014, respectively) in patients with inoperable LA-NSCLC, and at a cutoff of -0.198 stratified patients into two groups with 5-year OS rates of 39.8% and 8.8%, and 2-year PFS rates of 22.2% and 5.5% for the high- and low-immune signature groups, respectively. Using immune signature, we proposed immune signature nomograms, which were better than the traditional TNM staging system in terms of discriminating ability (OS: 0.692 vs. 0.588; PFS: 0.672 vs. 0.586, respectively) or net weight classification (OS: 32.96%; PFS: 9.22%), suggesting that immune signature plays a complementary role in the prognosis prediction of patients with inoperable LA-NSCLC. Conclusions: Multiple immune features based immune signature could effectively predict recurrence and survival of inoperable LA-NSCLC patients, and complemented the prognostic value of the TNM staging system.

e21721 Background: Accelerated reproliferation during radiation is a classic theory in radiobiology. The long intervals between cycles of chemotherapy provides a better micro-circumstance to reproliferate of cancer cells. Few studies explored the accelerated reproliferation among cycles of chemotherapy. Methods: Patients with inoperable stage III and stage IV lung cancer from Shandong Cancer Hospital and Institute were enrolled prospectively. Tumor tissue and sequential peripheral blood were obtained before treatment and among cycles of chemotherapy to detect Ki-67 and let-7a expression. All patients were followed up to observe the occurrence and survival. Results: Fifty-two consecutive consenting patients were enrolled prospectively. The median follow-up was 13 months (range, 2–62 months). A strong correlation was found between serum let-7a and tissue Ki-67 before treatment (r = − 0.667, P < 0.001). The serum let-7a expression level was significantly upregulated at the time point after 2 and 4 cycles of chemotherapy, respectively, compared with the original. Then, at the time point after 6 cycles of chemotherapy, the expression levels of let-7a returned to relatively low level (F = 7.994, P < 0.001). Patients with high level of baseline serum let-7a had significantly better OS and PFS than patients with relatively low level of baseline serum let-7a (The 1-year OS and PFS rates were 80.6% VS 33.3%, X2 = 12.81, P < 0.001, and 54.2% VS 20%, X2 = 8.001, P = 0.005, respectively). Conclusions: The study showed that serum let-7a could reflect the proliferation of tumor tissue reliably in lung cancer, with high prognostic value. Furthermore, the study showed that accelerated reproliferation exists during treatment of cancer, not only in radiotherapy, but also in chemotherapy, which can give us a new perspective to overcome drug resistance of lung cancer, and would help in determining individual treatment strategy. This project was supported by National Natural Science Foundation of China (Grant No. 81502667) and Key Research and Development Plan of Shandong, China (Grant No. 2016GSF201167).

e21030 Background: The clinical benefits of immunotherapy in patients with stage I non-small cell lung cancer (NSCLC) is still controversial. Immune status plays critical role in the development and progression of NSCLC, and is associated with the patient survival outcomes. The analysis of immune features is thus valuable for the determination of immunotherapy. However, one single immune feature cannot reflect the complex immune status, and its prognostic value is extremely limited. In this study, we aimed to construct an immunoscore classifier based on multiple immuno-genes to predict the prognosis of patients with early NSCLC. Methods: A total of 522 patients with stage I NSCLC were included in this study. All patients' follow-up records and gene expression data were completely preserved. A least absolute shrinkage and selection operator (LASSO) algorithm was used to screen immune-related genes, and a COX proportional hazard regression model was used to construct the immunoscore classifier based on multiple immune-genes. Besides, the net reclassification improvement (NRI) calculation and concordance index (C-index) were applied to quantify the improvement of usefulness added by the immunoscore classifier compared to TNM staging system. Results: The immunoscore classifier including CCL5, CD8A, CXCL9, HLA-DQA1, LAG3, STAT1, and CD276 was significantly correlated with OS (HR: 2.785 CI: 1.809-4.289 P < 0.001) in patients with stage I NSCLC. With the optimal cut-off value of 4.32, all patients can be divided into a low-risk immune group and a high-risk immune group. The 10-year survival rates of the two groups were 36.8% and 12.3%, respectively. Besides, the immunoscore classifier was superior to the traditional TNM staging system in terms of distinguishing ability (C-index improvement by 0.075) and net reclassification ability (NRI improvement by 11.29%), indicating that the immunoscore classifier plays an important role in improving prognostic value. Conclusions: Multiple immune-genes based immunoscore classifiers can effectively predict the prognosis of patients with stage I NSCLC, and is significantly superior to the traditional TNM staging system in terms of prediction effectiveness and accuracy. As a new assessment tool, the immunoscore classifier may be helpful for determining the immune status of patients with stage I NSCLC and screening patients suitable for subsequent immunotherapy.

e21669 Background: In the new era of immunotherapy, the regimen based on bevacizumab is still one of the standard options for treatment of advanced non-small cell lung cancer (NSCLC) patients without driver mutations. However, the prognostic factors for bevacizumab are still missing. We aimed to determine the integrative value of computed tomography (CT), epigenetic modifications, clinicopathological and systemic inflammatory factors for predicting the survival of advanced NSCLC patients with bevacizumab. Methods: Clinicopathological parameters, dynamic systemic inflammatory factors, radiomics features, and DNA methylation profiling in advanced non-squamous NSCLC patients receiving first- or second- line bevacizumab plus chemotherapy were included in this study. The prognostic radiomics signature were constructed by least absolute shrinkage and selection operator (LASSO) Cox analysis. A multi-omics prediction nomogram for progression-free survival (PFS) based on radiomics, clinicopathological and systemic inflammatory features was established and independently validated. Furthermore, radiomics signature-related DNA methylation were submitted to functional enrichment analysis. Results: Total of 272 patients were included in analysis, 224 in training cohort and 48 in validation cohort. Five radiomics features, including Information Measure Corr1, Inverse Variance, Local Std Max, Gauss Area, Spherical Disproportion, were finally selected to construct radiomics signature with the AUC of 0.71. Smoking history, anatomical feature, liver metastasis, LDH4, NLR2 and radiomics signature were found to be independent prognostic factors for PFS. A multi-omics nomogram was developed based on these features in training cohort with the C-index of 0.76, and external validated with the C-index of 0.75. The tissue slices of 20 patients receiving bevacizumab were used for DNA methylation profiling. Functional enrichment analysis indicated widespread and statistically significant associations between radiomics features and DNA methylation changes which involved in several pathways related to angiogenesis and immune system, such as Notch signaling pathway, small GTPase Rho signal transduction, TGFβ signal transduction. Conclusions: This multi-omics nomogram integrating radiomics, clinicopathological, systemics inflammatory features improved the prediction of PFS in advanced NSCLC patients receiving bevacizumab. And the radiomics signature were found to be related to angiogenesis and immune status.

Shuheng Shang,1,2 Yi Su,3 Zhaofeng Zhu,4 Butuo Li,2,5 Meiying Guo,1,2 Yiyue Xu,1,2 Xindong Sun,2 Linlin Wang,2 Jinming Yu2 1Department of Radiation Oncology, School of Medicine, Shandong University, Jinan, China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, China; 3Department of Radiotherapy, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Institution, Yantai, China; 4Department of Radiotherapy, Tai’an Central Hospital, Tai’an, China; 5Department of Radiation Oncology, Tianjin Medical University, Tianjin, China Background: The optimal treatment strategy for patients with non-small-cell lung cancer (NSCLC) with postoperative oligometastases is poorly defined. This two-institution analysis sought to retrospectively compare the efficacy and toxicity of local ablative treatment plus chemotherapy vs local treatment alone in patients with NSCLC who developed oligometastases after surgery.Patients and methods: Among patients who underwent surgery for stage I–III NSCLC, 163 patients with oligometastases were enrolled between 2005 and 2016 in this study. All patients had ≤5 metachronous metastases with a disease-free interval (DFI) of ≥6months after surgery. Patients with a second primary cancer, local recurrence, or driver mutations were excluded. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), failure patterns, and treatment-related toxicities were compared between groups receiving local ablative treatment plus chemotherapy and local treatment alone.Results: A total of 105 patients who underwent local ablative therapy combined with chemotherapy and 58 patients who received local ablative therapy alone were included in this study. The median follow-up was 19 (range, 1.5–107) months. The combination therapy group had a higher ORR than the local therapy alone group (66.7% vs 46.5%, P=0.012), while the median PFS was 10 vs 7months (P=0.006) and the median OS was 19 vs 18.5months (P=0.498), respectively. By multivariate analysis, combination therapy and DFI ≥24months were associated with superior PFS. Age was the only independent prognostic factor for OS (P

Butuo Li,1,2,* Cheng Li,3,* Meiying Guo,2,4 Shuheng Shang,2,4 Xiaogang Li,5 Peng Xie,2 Xindong Sun,2 Jinming Yu,1,2 Linlin Wang2 1Department of Radiation Oncology and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Tianjin, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, People’s Republic of China; 3Department of Dean’s Office, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Science, Jinan, People’s Republic of China; 4Department of Radiation Oncology, School of Medicine, Shandong University, Jinan, People’s Republic of China; 5Department of Radiation Oncology, School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, People’s Republic of China *These authors contributed equally to this work Background: The combination of bevacizumab and chemotherapy is still one of the standard treatments for advanced non-small-cell lung cancer (NSCLC) patients in the new era of targeted therapy. Although a high level of baseline lactate dehydrogenase (LDH) was found to predict survival benefit from bevacizumab in patients with metastatic colorectal cancer, the predictive value of serum level of LDH in NSCLC patients treated with bevacizumab has not been investigated yet. Moreover, dynamic evaluation of serum level of LDH changes may be more informative and promising in predicting patients’ prognosis. We thus sought to analyze LDH kinetics and evaluate its predictive role in the response and survival of advanced NSCLC patients treated with bevacizumab. Method: We retrospectively collected and analyzed a total of 161 advanced NSCLC patients who had undergone treatment with bevacizumab. Univariate and multivariate logistic regression analyses of serum level of LDH were used for response analyses, and Cox models for both overall survival (OS) and progression-free survival analyses (PFS). Longitudinal analysis of LDH was performed using a mixed-effect regression model. Results: On multivariate Cox models, increase of serum level of LDH after 4 cycles with bevacizumab (INC4) treatment was shown to be the independent risk factor for OS (hazard ratio =2.17, 95% CI: 1.21–3.90, P=0.009), and the serum level of LDH after 2 cycles (LDH2) and the increase of LDH after 6 cycles with bevacizumab (INC6) treatment were the predictive factors for PFS (hazard ratio =2.33, 95% CI: 1.38–3.93, P=0.001; hazard ratio =1.96, 95% CI: 1.27–3.03, P=0.002, respectively). Patients with increase of serum level of LDH after 2 cycles of treatment with bevacizumab (INC2) (odds ratio =3.75, 95% CI: 1.83–7.68, P

Introduction Locally advanced nonsmall‐cell lung cancer (LA‐NSCLC) represented a highly heterogeneous group, with more than half of the patients aged ≥65 years at the time of diagnosis. However, the optimal treatment for elderly LA‐NSCLC patients was still not defined. Methods A total of 33530 elderly patients (≥65 years) diagnosed with LA‐NSCLC from 2004 to 2014 were identified from Surveillance, Epidemiology, and End Results (SEER) database. Results Locally advanced nonsmall‐cell lung cancer patients aged 65‐74 years were more frequently treated with chemoradiotherapy (CRT) (40%), while patients aged ≥75 years received more best supportive care (BSC) (36%). For age group of 65‐74 years, patients who had surgery with or without (neo)adjuvant therapy had a median survival of 28 months, CRT 15 months, radiotherapy (RT) alone 6 months, chemotherapy alone 11 months, and BSC 3 months; while for patients aged ≥ 75 years, the median OS was 20, 13, 7, 9, and 2, respectively. Besides, independent clinicopathological factors were integrated into nomograms for OS and CSS prediction, C‐indexes achieved 0.692 and 0.698, respectively. Importantly, the discrimination of nomogram was superior to that of the American Joint Committee on Cancer TNM classification (0.742 vs 0.572 for training set and 0.731 vs 0.565 for validation set). Conclusion For elderly patients with LA‐NSCLC, the curative‐intent treatment (surgery or CRT) conferred better survival compared to chemotherapy alone, RT alone and BSC. The proposed nomograms based on independent clinicopathological variables may be practical and helpful for precise evaluation of patient prognosis, and guiding the individualized treatment for elderly LA‐NSCLC.

As the crucial issue in the development of anti‑angiogenic drugs is how to predict which patients will and will not benefit prior to the initiation of therapy, angiogenic 18F‑alfatide positron emission computed tomography (PET) was assessed in the present study. Lung adenocarcinoma A549 (high angiogenesis) and prostate PC‑3 (low angiogenesis) cell xenografted tumor‑bearing mice underwent 18F‑alfatide PET at baseline and following treatment with either an anti‑angiogenic therapy or vehicle. The evaluation index for the inhibition of tumor growth in the individuals in the treated groups was represented by treatment/control (T/C) ratio (%). Anti‑angiogenic responses were denoted by the changes in 18F‑alfatide uptake in the same animal. The T/C ratio was lower in high‑uptake tumors than in low‑uptake tumors (P=0.001). A significant difference in the tumor volumes between the anti‑angiogenic therapy group and the control group occurred earlier in the A549 model than in the PC‑3 model. 18F‑alfatide uptake decreased more for A549 tumors than for PC‑3 tumors following anti‑angiogenic therapy. In each treatment group, the degree of tumor response to anti‑angiogenic therapy was associated well with the tumor uptake prior to treatment (P

Concerns regarding end-of-life (EOL) chemotherapy are being increasingly raised. Tumor chemosensitivity may influence the decision for aggressive chemotherapy near the EOL. Data on EOL chemotherapy in highly chemosensitive tumors, such as small cell lung cancer (SCLC), are scarce. A total of 143 SCLC decedents were consecutively included. Data about clinical factors and treatment modalities were obtained from the electronic medical records. The relationships among EOL chemotherapy, clinical features, overall survival (OS), and aggressive care were investigated. About 64% of patients had chemosensitive disease. In total, 30.8 and 16.1% of patients received EOL chemotherapy within the last 1 and 2 months of life, respectively. Younger age was associated with a higher rate of EOL chemotherapy. We determined that EOL chemotherapy was related to inferior OS not only in the entire group, but also in the chemosensitive subgroup. Furthermore, more intensive care was observed among patients who underwent EOL chemotherapy compared with those who did not. EOL chemotherapy was correlated with shorter survival and more aggressive care in patients with SCLC. More research is needed to develop indications for terminating palliative chemotherapy, to help physicians and patients with their difficult choices.

Primary non-Hodgkin's lymphoma (NHL) of the vagina is uncommon. The present case study reports the case of a 54-year-old female with a palpable mass between the rectum and vagina. The patient presented with symptoms consistent with vaginal cancer but lacked any of the 'B' symptoms often associated with systemic lymphoma, including fever, weight loss, night sweats and fatigue. The mass was resected under anesthesia. Immunohistochemistry and biopsy confirmed diffuse large B-cell NHL (DLBCL). Following surgery, six cycles of chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone were administered. Subsequently, a vertebral body metastasis was observed using a computed tomography scan and whole-body bone imaging. The patient received palliative radiation for the vertebral body metastasis. Additionally, the available literature was reviewed in order to further characterize this rare disease.

Intramuscular myxoma (IMM) as a rare soft-tissue tumor arising from the muscles is completely benign. When IMM accompanies malignance, it may be misdiagnosed as muscle metastasis, and for this extremely rare concurrence, the subsequent treatment would vary accordingly. The current study presents, to the best of our knowledge, the first case of non-small cell lung cancer (NSCLC) concomitant with IMM mimicking skeletal muscle metastasis. A 64-year-old female was hospitalized with a history of chest discomfort and right lumbar pain that had persisted for four months. The computed tomography scan showed a lesion in the left upper lobe of the lung and the right psoas, respectively. Serum biomarkers for NSCLC were abnormal. A presumptive clinical diagnosis was compatible with left NSCLC and right psoas muscle metastasis (cT2aN3M1b, stage IV). Stage IV lung cancer would receive palliative treatment. However, the final diagnosis of synchronous left lung squamous cell carcinoma (cT2aN3M0, stage IIIB) and IMM in the right psoas was confirmed by biopsy. The patient therefore underwent definitive chemoradiotherapy for lung carcinoma, and conservative treatment, including analgesics, for IMM. The diagnosis process for a malignant neoplasm concomitant with IMM is not straightforward due to a lack of clinical experience, and it significantly affects the tumor staging and subsequent treatment strategy. The present case suggests that IMM should be included in the differential diagnosis when an abnormal intramuscular lesion concomitant with malignancy is identified. The value of histopathological diagnosis prior to definitive treatment also requires highlighting.

Background Acute radiation-induced esophagitis (ARIE) is one of main toxicities complicated by thoracic radiotherapy, influencing patients' quality of life and radiotherapy proceeding seriously. It is difficult to be cured rapidly so far. Our phase I trial preliminarily showed that EGCG may be a promising strategy in the treatment of ARIE. Materials and methods We prospectively enrolled patients with stage III lung cancer from the Shandong Tumor Hospital & Institute in China from January 2013 to September 2014. All patients received concurrent or sequential chemo-radiotherapy, or radiotherapy only. EGCG was administrated once ARIE appeared. EGCG was given with the concentration of 440μmol/L during radiotherapy and additionally two weeks after radiotherapy. RTOG score, dysphagia and pain related to esophagitis were recorded every week. Results Thirty-seven patients with stage IIIA and IIIB lung cancer were enrolled in this trial. In comparison to the original, the RTOG score in the 1st, 2nd, 3rd, 4th, 5th week after EGCG prescription and the 1st, 2nd week after radiotherapy decreased significantly ( P =0.002, 0.000, 0.000, 0.001, 0.102, 0.000, 0.000, respectively). The pain score of each week was significantly lower than the baseline ( P =0.000, 0.000, 0.000, 0.000, 0.006, 0.000, 0.000, respectively). Conclusion This trial confirmed that the oral administration of EGCG is an effective and safe method to deal with ARIE. A phase III randomized controlled trial is expected to further corroborate the consequence of EGCG in ARIE treatment.

Rationale: The pathogenesis and progression of lung cancer is a complicated process in which many genes take part. But molecular gene testing is typically only performed in advanced-stage non-squamous non-small-cell lung cancer (NSCLC). The value of tyrosine kinase inhibitors (TKI) administration is not widely recognized with respect to early-stage NSCLC. Patient concerns: Here, we present a case of a man, heavy smoker who initially presented with stage IA lung adenocarcinoma (LADC). Three years after a lung lobectomy, he was diagnosed with advanced lung squamous cell carcinoma (SCC), according to laboratory, imaging, and pathological examinations. Diagnoses The case initially had an early-stage LADC with an L858R epidermal growth factor receptor (EGFR) mutation. A subsequent advanced SCC bearing EGFR L858R/T790M mutations occurred 3 years after surgery. Interventions: The comprehensive therapy we utilized, including surgical resection for the early-stage lesion and GP chemotherapy and local radiotherapy as the first line therapy along with gefitinib maintenance treatment for the advanced metachronous second primary tumors (MST). Outcomes: The synthetical therapy, have resulted in our patient with remaining alive and progression free for 4.5 years. Lessons: This case suggests that changes in molecular pathology should be monitored closely throughout cancer progression to guide personalized therapy and improve prognosis. We further review administration of TKI to early-stage NSCLC and to the metachronous second primary tumors (MST) in survivors.

Despite administration of prophylactic cranial irradiation (PCI), some small cell lung cancer (SCLC) patients still suffer from brain metastases (BM) with unknown risk factors. We conducted this study to identify patients with higher BM risk after PCI and improve their outcome. The characteristics and survival of all the SCLC patients underwent PCI in our institute from 2003 to 2014 were analyzed. Kaplan-Meier method was applied to estimate BM free survival (BMFS) and overall survival (OS). Cox regression analyses were performed to explore risk factors for BM. A total of 175 patients with the median age of 55 years (range, 29–76) were eligible, among whom 36 (20.6%) developed BM with median follow-up of 42 months. Both univariate and multivariate analyses showed HART and TNM classification (p p > 0.05). Stage IIIB-IV and HART were independent risk factors for BM after PCI in SCLC. TNM classification was more valuable on prognosis than two-stage system. Further large-scale studies are needed to confirm our findings.

The aim of the current study was to investigate the prognostic significance of epidermal growth factor receptor (EGFR) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) receiving concurrent chemoradiotherapy (CCRT). In total, 47 patients with locally advanced ESCC who were treated with CCRT were included in the present study. The chemotherapeutics comprised of 5-fluorouracil (750–1,000 mg/m2/day; days one to five) and cisplatin (30 mg/m2/day; days one to three) in combination with radiation therapy (~60 Gy), which was performed as the initial treatment. EGFR expression was compared with the clinicopathological features, local recurrence, metastasis status and overall survival (OS). Overall, EGFR overexpression (percentage of immunoreactive tumor cells, ≥50%) was identified in 59.6% of the patients. The median survival time (MST) of the EGFR-positive group was 15 months and the MST of the EGFR-negative group was 23.5 months. A significant correlation was observed between EGFR overexpression and poor OS (P=0.024). EGFR overexpression was found to exhibit a correlation with lymph node metastasis (P=0.011), but no correlation was identified with other clinicopathological features. In addition, a correlation was identified between OS and gender (P=0.021), age (P=0.018), depth of invasion stage (P=0.035) and tumor location (P=0.023). EGFR overexpression determined by pretreatment biopsy may be a clinically useful biomarker for predicting the OS of ESCC patients.

8508 Background: Cisplatin-based chemotherapy as adjuvant therapy for resected NSCLC has reached its plateau, and was limited by high risk of recurrence and significant toxicities. The clinical value of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in resected non-small cell lung cancer (NSCLC) harboring EGFR mutations remains controversial. In this study, we performed a meta-analysis to evaluate the role of EGFR inhibitors as adjuvant therapy for targeted patients. Methods: Studies were identified via an electronic search on Pubmed, EMBASE, ISI Web of Science, ScienceDirect, SpringerLink, The Cochrane library and so on. Pooled odds ratio (OR) for disease-free survival (DFS) and overall survival (OS) were calculated for meta-analysis. Registration number: PROSPERO (CRD42018093144). Results: There were 11 trials (1,152 resected NSCLC patients with EGFR sensitive mutations) in this meta-analysis. Results showed that adjuvant treatment with EGFR-TKIs can prolong both OS and DFS when compared to treatment without TKIs as adjuvant therapy (OS: OR, 0.63; 95% CI, 0.46 to 0.87, P = 0.004; heterogeneity I2= 61%, P = 0.008; DFS: OR, 0.56; 95% CI, 0.43 to 0.72, P < 0.00001; heterogeneity I2= 37%, P = 0.1). Results of predefined subgroup analyses in this meta-analysis suggested a greater DFS with EGFR-TKI mono compared with chemotherapy, whereas the OS benefit failed to show a similar difference between the two arms (p = 0.3). And we also find that treatment with EGFR-TKI plus chemotherapy was associated with significantly longer DFS as well as OS than chemotherapy mono in patients with completely resected EGFR-mutant NSCLC (DFS: OR, 0.48; 95%CI, 0.34-0.68; P < 0.00001; heterogeneity I2= 15%, P = 0.29; OS: OR, 0.50; 95% CI, 0.31-0.78; P = 0.003; heterogeneity I2 = 57%, P = 0.05). And less grade 3 or higher AEs were observed in the TKIs group (OR, 0.22; 95% CI, 0.14 to 0.37, P < 0.00001; heterogeneity I2= 22%, P = 0.28). Conclusions: Adjuvant EGFR-TKIs may be a potential treatment option compared to adjuvant chemotherapy in completed resected patients with EGFR mutation-positive NSCLC. This project was supported by the National Natural Science Foundation of China (Grant No. 81502667), Key Research and Development Plan of Shandong, China (Grant No. 2016GSF201167).

Xiaoli Zhang,1,2 Jinming Yu,1,2 Minghuan Li,2 Hui Zhu,2 Xindong Sun,2 Li Kong2 1Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong Province, People’s Republic of China Background: The association of high mobility group box 1 (HMGB1) expression with clinicopathological significance and prognosis in Asian patients with colorectal carcinoma (CRC) remains controversial. The purpose of this study was to conduct a meta-analysis and literature review to identify the role of HMGB1 in the development and prognosis of CRC in Asians. Methods: All eligible studies regarding the association between HMGB1 expression in tissue with clinicopathological significance and prognosis in Asian patients with CRC published up to January 2015 were identified by searching PubMed, Web of Science, Chinese National Knowledge Infrastructure, and WanFang database. Analysis of pooled data was performed, while odds ratio (OR) or hazard radio with 95% confidence interval (CI) was calculated and summarized to evaluate the strength of this association in fixed- or random-effects model. Results: The expression level of HMGB1 in CRC tissues was much higher than normal colorectal tissues (OR =27.35, 95% CI 9.32–80.26, P

Purpose Accurate staging of mediastinal lymph nodes metastases is critical for determining the application of stereotactic body radiation therapy (SBRT) for patients with early stage non-small cell lung cancer (NSCLC). In this multicenter study the accuracy of 18 F-FDG PET/CT to detect lymph node metastases was evaluated for early stage NSCLC. Materials and methods The data from the patients with stage1 NSCLC who received preoperative 18 F-FDG PET/CT staging and radical surgery was retrospectively reviewed of five centers from February 2004 to August 2010. The lymph node metastases were confirmed histopathologically after radical surgery. And the sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) were calculated for PET/CT staging. Results Two hundred patients were enrolled. The sensitivity, specificity, accuracy, PPV and NPV for lymph node metastases on PET/CT were 44%, 83%, 78%, 29% and 91%, respectively. There were eight and 19 cases positive for lymph node metastases with central ( n =62) and peripheral ( n =138) NSCLC ( P> 0.05), respectively. Conclusion 18 F-FDG PET/CT was specific in N 0 staging for T 1–2 NSCLC. The NPV was about 91% in clinical N 0 patients, suggested that 18 F-FDG PET/CT may help to accurately stage N 0 patients and thus identify patients for SBRT.

Background Accelerated reproliferation, usually deemed to occur late during the course of radiation therapy, is an important factor resulting in radiotherapy failure. The identification of strategies that accurately reflect accelerated reproliferation might help to determine radiotherapy strategy, and thus implementation of individualized treatment. Patients and Methods Patients with lung cancer were enrolled from Shandong Cancer Hospital and Institute in China between March 2014 and March 2015. Tumor tissue and sequential peripheral blood samples were obtained before treatment and during radiotherapy to detect Ki-67 and let-7 expression. Results We found a strong correlation between serum let-7 and tissue Ki-67 before treatment (r = −0.773; P = .003). Patients with a high level of baseline serum let-7 expression level had significantly better overall survival (the overall survival were 100% and 27.3%, respectively; P = .024). For patients with a relatively low expression level of baseline serum let-7, there was a peak of expression levels at week 4 (the mean expression levels were 1.40, 5.01, and 1.36, respectively). However, for patients with relatively high expression levels of baseline serum let-7, the expression levels were constantly downregulated at week 4 and 6 compared with the original (the mean expression levels were 6.16 vs. 1.34 vs. 0.80, respectively). Conclusion The study showed that serum let-7 expression level could reflect the proliferation of tumor tissue reliably in patients with lung cancer. Furthermore, the study might change conventional views of accelerated reproliferation. We showed that initial accelerated proliferation exists in patients with a relatively slow proliferation rate before radiotherapy, and late course accelerated reproliferation exists in patients with relatively fast proliferation before radiotherapy.

UNLABELLED Outcomes are suboptimal when molecularly targeted therapies are used in patient populations unselected for the molecular target. This pilot study examines the correlation of PET using (11)C-labeled 4-N-(3-bromoanilino)-6,7-dimethoxyquinazoline ((11)C-PD153035), an imaging biomarker of epidermal growth factor receptor (EGFR), with outcomes in patients with non-small cell lung cancer (NSCLC) treated with the EGFR tyrosine kinase inhibitor erlotinib. METHODS Patients with advanced chemotherapy-refractory NSCLC were prospectively enrolled on a trial of erlotinib at a dose of 150 mg daily and imaged by (11)C-PD153035 PET/CT at baseline, after 1-2 wk, and after 6 wk from the start of treatment. Overall survival and progression-free survival (OS and PFS, respectively) times were correlated with the (11)C-PD153035 standardized uptake value (SUV) at each of the imaging times. RESULTS Twenty-one patients were enrolled. Follow-up to progression was complete in all patients and to death in 18 of 21. By Cox regression analysis, baseline maximum SUV correlated strongly with OS and PFS (hazard ratio = 0.40, P = 0.002, and hazard ratio = 0.044, P < 0.001, respectively) independent of histology. Patients with higher maximum SUV (≥median) survived more than twice as long as patients with lower maximum SUV (median OS = 11.4 vs. 4.6 mo, P = 0.002; PFS = 4.4 vs. 1.8 mo, P < 0.001). However, (11)C-PD153035 uptake on follow-up scans was less well correlated with survival. CONCLUSION Our preliminary results suggest (11)C-PD153035 PET/CT may be a noninvasive and rapid method for identifying patients with refractory advanced NSCLC of adenocarcinoma or squamous histology likely to respond to the EGFR tyrosine kinase inhibitor but not for monitoring treatment response.

The purpose of this meta-analysis was to evaluate the prognostic value of standard uptake value (SUV) from serial Fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with head and neck cancer.We searched for articles limited to head and neck cancer, dealt with the impact of SUV on survival and published in English. The endpoints were disease-free survival (DFS), overall survival (OS), and local control (LC). Two reviewers extracted data independently.Thirty-five studies were identified; of which, 26 studies involving 1,415 patients met the inclusion criteria. Pooled survival data suggested better DFS, OS, and LC in patients with low SUV of pre-treatment, and the odds ratio (OR) was 0.23, 0.24, and 0.27, respectively. Patients having tumors with low SUV of post-treatment also had significantly better DFS (OR = 0.17) and OS (OR = 0.28) than those with high SUV.The present meta-analysis showed that (18)F-FDG uptake, as measured by the SUV before treatment and metabolic response after treatment, are valuable for predicting long-term survival in head and neck cancer. High (18)F-FDG uptake may be useful for identifying patients requiring more aggressive treatment.

A treatment planning comparison study was performed to evaluate the dosimetric characteristic and treatment efficiency of volumetric modulated arc therapy with step-and-shoot intensity modulated radiotherapy (IMRT) for the hypofractionated stereotactic radiotherapy (HFSRT) in patients with multiple brain metastases. CT datasets of 10 patients with two to four brain metastases were selected for the comparison. Three plans were generated for each case: seven-field step-and-shoot IMRT, single (RA1) and double (RA2) arcs with RapidArc technique (RA, Varian Medical System). The prescribed dose was 50 Gy in 10 fractions and plans were all normalized to the mean dose to the PTV. For PTV, plans aim to achieve at least 98% of PTV was covered with the 95% of prescription dose, at least 95% of PTV was encompassed by the prescription dose, and an over-dosage of 110% of the prescription dose was allowed to 5% volume of the PTV. The plans generated using three techniques were clinically acceptable. The target conformity and homogeneity were improved slightly with RA2 compared to IMRT and RA1. The Paddick CI was 0.868 (IMRT), 0.863 (RA1) and 0.895 (RA2), and HI was 7.7 (IMRT), 7.5 (RA1) and 6.5 (RA2), respectively. Compared with IMRT, the maximum dose in RA2 plans to the brainstem, left and right optic nerves, left and right lens was reduced by 1.6 Gy, 6 Gy, 3 Gy, 1.5 Gy, 1.3 Gy, respectively. The percentage of healthy tissue volume receiving 5 Gy was larger with RA1 (56.7%) and RA2 (57.1%) than with IMRT (52.9%), while the percentages of volume receiving 15 Gy and 20 Gy were smaller with RA1 (27.1%, 18.7%) and RA2 (25%, 16.3%) than with IMRT (28.8%, 19.1%). No significant difference was observed between RA1 and RA2. The mean number of MU per fraction of 5 Gy was 1944 ± 374 (IMRT), 1199 ± 173 (RA1) and 1387 ± 186 (RA2), respectively. Compared with IMRT, the MUs were reduced by 36.8% and 27.2% with RA1 and RA2. The pure beam-on time needed per fraction was 6.5 ± 1.2 min (IMRT), 1.25 min (RA1) and 2.5 min (RA2), respectively. The beam-on time for RA1 and RA2 was approximately 80% and 40% less compared to IMRT. In conclusion, RA, single arc or double arcs, is a feasible technique with highly conformal dose distribution for the HFSRT in patients with oligo brain metastases. Compared with IMRT, RA1 provides similar plan quality, while RA2 achieves slight improvements in PTV coverage and sparing of organs at risk. The treatment efficiency, using less monitor units and shorter treatment delivery time, is the most obvious advantage.

The purpose of this study was to evaluate the prognostic value of metabolic tumor volume (MTV) and metabolic index (MI) from fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in patients with nasopharyngeal carcinoma (NPC).From October 2002 to July 2004, 41 patients with NPC who underwent (18)F-FDG PET-CT scan before and after radiotherapy were reviewed retrospectively. All patients received intensity-modulated radiotherapy using 6MV X-rays. We examined the association of MTV and the results of long-term follow-up of the patients.Patients having tumors with an MTV below 30 cm(3) had significantly better 5-year overall survival (OS) (84.6:46.7%, P = 0.006) and disease-free survival (DFS) (73.1:40.0%, P = 0.014) than patients with an MTV of 30 cm(3) or greater. And the patients with MI below 130 had significantly higher 5-year OS (88.0:43.8%, P = 0.002) and DFS (76.0:37.5%, P = 0.005) than other patients. In the Cox multivariate analysis, MI and metabolic response (MR) were predictive of DFS, and we did not find a significant relationship between standard uptake value (SUV) and OS or DFS.The present study shows that tumor volume parameters, especially the combination of MTV and SUV in the "metabolic index", are valuable for predicting long-term survival. High MI may be useful for identifying patients requiring more aggressive treatment.

OBJECTIVES To determine the prognostic value of standardized uptake value (SUV) of F-fluorodeoxyglucose by serial positron emission tomography and computed tomography (PET/CT) in nonsmall cell lung cancer (NSCLC). METHODS Forty-seven patients (37 male, 10 female) with NSCLC in stage III were enrolled. All patients had at least 2 serial F-fluorodeoxyglucose PET/CT scans, both before and after therapy, and the maximum standardized uptake value (SUVmax) of the primary lung lesion was calculated. The value changes of SUVmax before and after treatment were calculated according to the following equation: DeltaSUV = (SUVbefore - SUVafter) x 100%/SUVbefore. RESULTS Of the 47 eligible patients, after a median follow-up of 23.5 months (range, 13-34 months), 26 patients had local and regional recurrence or metastasis and 21 remained disease-free. Significant differences in SUVmax were observed either before (P1 = 0.003) or after (P2 = 0.002) treatment between the 2 groups. However, the percent change of SUVmax before and after therapy were not significantly different (P = 0.054). CONCLUSIONS SUV from 2 serial PET/CT scans, before and after concurrent chemoradiotherapy were significant predictors for local and regional recurrence or metastasis. SUV is a significant predictor for local and regional recurrence or metastasis in patients of NSCLC.

Radiation dose escalation is limited by the high incidence of pulmonary and esophageal toxicity, leading to calls for the omission of elective nodal irradiation (ENI) and the willingness to use involved-field irradiation (IFI) in patients with nonsmall cell lung cancer (NSCLC).A total of 200 eligible patients with inoperable stage III NSCLC were treated with concurrent chemoradiotherapy and randomized into either an IFI or ENI arm. A total of 4 to 6 cycles of cisplatin-based chemotherapy were delivered, and concurrent radiotherapy was started after the second cycle of chemotherapy. Three-dimensional conformal radiotherapy was delivered in once-daily fractions of 1.8 to 2 Gy to 68 to 74 Gy for IFI or 60 to 64 Gy for ENI.Patients in the IFI arm achieved better overall response rate (90% vs. 79%, P = 0.032) and better 5-years local control rate (51% vs.36%, P = 0.032) than those in the ENI arm. The radiation pneumonitis rate in patients with IFI was lower than in patients with ENI (17% vs. 29%, P = 0.044), and similar trends appeared in the radiation esophagitis, myelosuppression, and radiation pericarditis between 2 study arms, although not significantly. The 1-, 2-, and 5-year survival rates were 60.4%, 25.6%, and 18.3% for the ENI arm and 69.9%, 39.4%, and 25.1% for the IFI arm, respectively. Only the 2-year survival rates were statistically significant (P = 0.048).IFI arm achieved better overall response and local control than ENI arm, and it allowed a dose of 68 to 74 Gy to be safely administered to patients with inoperable stage III NSCLC. Outcome improvement can be expected by conformal IFI combined with chemotherapy for stage III NSCLC.

Purpose: To determine the optimal clinical target volume (CTV) margins around the nodal gross tumor volume (GTV) in non–small-cell lung cancer (NSCLC) patients by assessing microscopic tumor extension beyond regional lymph node capsules. Methods and Materials: The incidence of nodal extracapsular extension (ECE) and relationship with nodal size were reviewed in 243 patients. Histologic sections of dissected regional lymph nodes up to 30 mm in size were examined to measure the extent of microscopic ECE. We determined the distribution of cases according to extent of ECE and the relationships between ECE extent and lymph node size, regional nodal disease extent, histologic type, and degree of differentiation. Results: The nodal ECE was seen in 41.6% of patients (101/243) and 33.4% of lymph nodes (214/640), and the incidence correlated to larger lymph node size positively. The extent of ECE was 0.7 mm in mean (range, 0–12.0 mm) and ≤3 mm in 95% of the nodes. Positive correlations were found between extent of ECE and larger lymph node size (≥20 mm vs. 10–19 mm or p = 0.005), advanced nodal stage (N2 vs. N1, p = 0.046), and moderate or poor (vs. good or unknown) nodal differentiation ( p = 0.002). ECE did not differ significantly by histologic type or nodal station. Conclusions: The incidence of ECE related to lymph node size, and ECE extent related to lymph node size, stage, and differentiation. It may be reasonable to recommend 3-mm CTV margins for pathologic lymph nodes

Objective: To evaluate the relationship between 99m Tc-HL91 ( 99m Tc labeled 4,9-diaza-3,3,10,10-tetramethyldodecan-2,11-dione dioxime) SPECT (single photon emission computed tomography) hypoxia imaging and the treatment outcome and also to assess changes in tumor oxygenation during the course of radiotherapy. Methods: There were 32 patients enrolled in the study with pathologically proven nonsmall cell lung cancer that received 3-dimensional conformal radiotherapy. A 99m Tc-HL91 SPECT scan was performed in all patients 1 or 2 days before radiotherapy and repeated during and after radiotherapy completion in 18 patients. The radioactivity ratios of tumor to normal tissue (T/N) were calculated. Results: The relationship between T/N ratios at 4 hours images after injection that was shown as the best of 3 acquired images before radiotherapy and tumor response and over survival were analyzed for all 32 patients. The results of 99m Tc-HL91 imaging of 32 patients correlate well with tumor response (P = 0.002) and also patient survival (P = 0.043). The T/N ratios of 18 patients were decreased before, during and after radiotherapy and there was significant statistic difference (P = 0.000...). Conclusions: HL91 SPECT imaging identified the hypoxia status and changes during radiotherapy in lung cancer. It was confirmed that hypoxia imaging with HL91 SPECT before radiotherapy may predict tumor response and patient survival.

e23100 Background: PET imaging with 18F-fluorothymidine (18F-FLT) can potentially be used to identify tumor subvolumes for selecting dose escalation in radiation therapy. The aim of this study was to monitor tumor cell proliferation and repopulation during fractionated radiotherapy and investigated the spatial concordance of tumor cell proliferation and repopulation with 18F-FLT tracer uptake. Methods: Mice bearing A549 xenograft tumors were assigned to 5 different irradiated groups (3f/6d, 6f/12d, 9f/18d, 12f/24d and 18f/36d) with 2 Gy/fractions and non-irradiated group. Serial 18F-FLT micro PET scans were performed at different time points, the maximum of standard uptake value (SUVmax) were measured to detect the feasible time of tumor repopulation during irradiation. Ex vivo images of the spatial pattern of intratumor 18F-FLT uptake and Ki-67 labeling index (LI) were obtained from thin tumor tissue sections. A layer-by-layer comparison between SUVmax and Ki-67 LI results, including the thresholds at which maximum overlap occurred between FLT-segmented areas and areas of active cell proliferation, were conducted to evaluate the spatial imaging pathology correlation. Results: The SUVmax were observed decreases in the 3f/6d group (P = 0.000), compared to these for non-irradiated tumors. However, it was significantly increased in the 6f/12d later, and then gradually reduced with treatment time prolonged again after 6f/12d group. Proliferation changes on pathology imaging at 6f/12d were also confirmed. Significant correlations were found between the SUVmax and Ki-67 LI of all ROIs in each in vitro tumor of cell proliferation group (Ps < 0.001). Similar results were also found in each tumor of accelerated repopulation group (Ps < 0.001). Furthermore, both of the mean ORRs were more than 50% in all layer of the tumor cell proliferation and accelerated groups. Regions of high-intensity 18F-FLT uptake in the autoradiographs exhibited prominent staining for Ki-67. Conclusions: 18F-FLT PET may be a promising imaging surrogate of tumor proliferative response to fractionated radiotherapy and might help make adaptive radiation oncology treatment plan.

Brain metastases (BM) are common and disastrous occurrence in patients with non-small cell lung cancer (NSCLC). Currently increasing studies suggest remarkable efficacy and mild toxicity of the epidermal growth factor tyrosine kinase inhibitor (EGFR TKI) in these patients, making targeted therapy an attractive option to BM from NSCLC. We here present a review about the use of EGFR-TKIs in this context and the following questions would be discussed: Are TKIs capable of permeating across brain–blood barrier (BBB)? How to boost exposure of EGFR TKI in cerebrospinal fluid to overcome the resistance of refractory metastases? Would the combination with other treatment like radiotherapy bring about advanced effect? And which patients with BM is the fittest population to EGFR-TKI treatment? In fact, though the administration of EGFR TKI only could achieve certain effect with limited penetration across BBB, increasing dose and combined radiotherapy would carry out better outcome. Unsurprisingly EGFR mutations were still the most important predictor of the sensitivity.