Epidemiological studies on wildfire smoke exposure and its associated disease morbidities and mortalities are rapidly accumulating in recent years. However, the findings of the existing studies have not been quantitatively evaluated with a conclusion. We conducted a systematic review and meta-analysis for the studies focused on associations of wildfire-sourced particles (PM2.5 and PM10) with cardiorespiratory diseases and mortality. We reviewed all literatures related to wildfire particles (PM2.5 and PM10) and cardiorespiratory disease morbidities [hospital admission, emergency department (ED) visits] and mortality (all-cause and cause-specific) from January 1, 2000 to August 1, 2024. Meta-analyses were conducted to summarize Relative Risks (RRs) and 95% confidence intervals (CIs) across studies when at least three studies were available for a particular exposure-outcome. All articles were assessed for risk of bias using a standard tool (Grading of Recommendations Assessment, Development and Evaluation, GRADE) for quality assurance. Studies (N = 45) were increasingly published between the years of 2020-2024 and from North America (N = 21) and Australia (N = 11) where wildfires are common. In the meta-analysis of over 124 million patients, wildfire smoke was consistently associated with increased risk of all-cause mortality (RR: 1.02, 95% CI 1.01-1.03 for PM2.5 per 10 μg/m3) and respiratory outcomes, including hospital admission (1.04, 95% CI 1.02-1.05 for wildfire PM2.5 and 1.01, 95% CI 1.00-1.02 for wildfire PM10) and ED visits (1.04, 95% CI 1.02-1.06 for wildfire PM2.5). Associations between wildfire PM2.5 and cardiovascular diseases were inconclusive (mortality: 1.02, 95% CI 1.01-1.03; hospital admission: 1.01, 95% CI 1.00-1.02; ED visit: 1.01, 95%CI: 0.98-1.04). Current studies provide evidence of an increased risk of hospitalization and ED visits for respiratory diseases and all-cause mortality due to wildfire PM2.5 and PM10 exposures worldwide. Future research is needed to explore health effects of wildfire exposure on cardiovascular diseases.

ABSTRACTIntroductionTo identify high‐risk patients for recurrence in resected stage IA lung adenocarcinoma and evaluate the impact of adjuvant chemotherapy (ACT) on their prognosis, as well as explore potential novel adjuvant therapies.MethodsConsecutive stage IA patients with ≥ 5% solid or micropapillary subtypes were analyzed. A nomogram was developed using Cox proportional hazards regression to predict recurrence‐free survival (RFS). In the high‐risk group after stratification, RFS was compared between patients receiving ACT and those under observation, as well as between patients with and without driver gene alterations.ResultsThis real‐world study included 1328 patients, with a 5‐year RFS of 79.0%. T stage and predominant subtype were independent risk factors for RFS. Patients with T1c or solid/micropapillary‐predominant tumors were stratified into a high‐risk group (n = 483) using the nomogram. A significant difference in 5‐year RFS was observed between the high‐ and low‐risk groups (73.6% vs. 84.3%, p < 0.001). Among high‐risk patients, sixty‐seven (13.8%) received ACT; however, there was no improvement in 5‐year RFS compared to observation alone (69.1% vs. 75.0%, p = 0.655). Testing rates for EGFR mutation and ALK fusion among high‐risk patients were only 52.4% and 43.9%, respectively, while mutation rates reached up to 55.7% and 9.4%, respectively. These molecular alterations exhibited numerically worse 5‐year RFS compared to wild‐type (EGFR mutation, 70.6% vs. 87.8%, p = 0.108; ALK fusion, 66.3% vs. 73.6%, p = 0.404), though not significant.ConclusionsACT failed to meet the needs of stage IA patients with histological high‐risk features. Further exploration of effective adjuvant target therapies is warranted for this patient subgroup.

Background: Immunotherapy has been recommended for neoadjuvant therapy in patients with locally advanced non-small cell lung cancer (NSCLC). However, its effect on surgical resection has not yet been examined. This study aimed to examine the effect of induction immunotherapy on surgical resection in terms of the surgical approach, resection extent, and perioperative recovery. Methods: We performed a real-world study comprising consecutive patients with clinical stage IB-IIIB NSCLC who received surgical resection after induction immunotherapy from January 2019 to September 2021. The perioperative outcomes were compared in terms of the surgical approach and resection extent. Results: Among 68 patients, 37 (54.4%) achieved a clinical objective response. Standard resection was performed in 37 patients (54.4%), while extended resection was necessary in the other 31 patients (45.6%). Minimally invasive surgery (MIS) was attempted in 37 cases (54.4%), with only 1 (2.7%) conversion. MIS was significantly more commonly accomplished in patients with a clinical objective response than those without (67.6% vs. 35.5%, P=0.008). Patients with a clinical objective response were more likely to have their tumors removed via MIS and/or standard resection (75.7% vs. 51.6%, P=0.04), while those without a clinical objective response more often required extended resection using an open approach. Patients receiving standard resection or MIS had significantly better perioperative outcomes than those who underwent extended resection or thoracotomy (all P<0.05). Conclusions: The results of this large single-center retrospective cohort indicate that in terms of a better clinical response, effective induction immunotherapy could help reduce the resection extent and/or provide more opportunities to perform MIS, resulting in better recovery.

Postoperative radiotherapy (PORT) is crucial for patients with thoracic locally advanced esophageal squamous cell carcinoma (LA-ESCC, pT3-4aN0-3M0) following esophagectomy. However, the appropriate radiation volume has not been well established. This study aimed to determine the optimal PORT volume for LA-ESCC patients. LA-ESCC patients post-esophagectomy were randomly assigned to either the large-field irradiation (LFI, primary lesion and lymph node tumor bed plus elective nodal irradiation) group or the small-field irradiation (SFI, primary lesion and lymph node tumor bed alone) group. Stratification was based on T stage and the number of lymph node metastases. The primary endpoint was disease-free survival (DFS), while the secondary endpoints included overall survival (OS), adverse events, and patterns of initial failure. A total of 401 patients were randomly assigned to the intention-to-treat analysis(LFI group, n = 210; SFI group, n = 191). The median DFS of patients in the LFI group was 47.9 months and 48.1 months in the SFI group (HR = 0.87, 95

OBJECTIVE:To clarify whether systemic LND influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT).SUMMARY OF BACKGROUND DATA:Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification.METHODS:This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence, and survival outcomes were analyzed in the nCRT group.RESULTS:Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P = 0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (hazard ratio, 0.358; P < 0.001) and disease-free survival (hazard ratio, 0.415; P = 0.001), but without any negative impact on postoperative complications. Less LND (<20 vs ≥20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P = 0.004) and total recurrence rates (41.2% vs 25.8%, P = 0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥20, but not in those with LND <20.CONCLUSIONS:Systemic LND does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local diseasecontrol. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

Background and purpose: More and more patients with multiple primary early-stage lung cancer are choosing to receive stereotactic body radiation therapy (SBRT), and this study aimed to retrospectively analyze the efficacy and prognostic factors of SBRT. Methods: In this study, patients who underwent SBRT at Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine from August 2014 to December 2020 and who met the inclusion criteria were included. Patients with multiple primary early-stage lung cancer were examined for efficacy and prognostic factors. After using propensity score matching (PSM), the difference in efficacy of SBRT between single and multiple primary early-stage lung cancer was observed. Results: This study included 241 early-stage lung cancer patients with SBRT, including 94 patients with multiple primary early-stage lung cancer. The 3- and 5-year local control rate (LC), progression-free survival (PFS) and overall survival (OS) were 87.1% and 71.3%, 84.0% and 66.9%, 93.3% and 79.3% in multiple primary early-stage lung cancer, respectively. Patients with multiple primary early-stage lung cancer did not experience any grade 3 or higher pulmonary toxicity with an overall toxicity incidence of 54.3%, and grade 2 toxicity occurred in 24 patients (25.5%). There was a total of 18 (19.1%) recurrences, and there were 3 (3.2%), 1 (1.1%), 12 (12.7%) and 2 (2.1%) patients with multiple primary early-stage lung cancers who experienced local recurrence, regional recurrence, distant metastasis and uncertain death, respectively. Patients with multiple primary early-stage lung cancer and those with single primary early-stage lung cancer had significant differences in clinical features prior to PSM. After PSM, there were 56 patients with multiple primary early-stage lung cancer and 56 patients with single primary early-stage lung cancer, and there was no statistically significant difference in LC (P = 0.291), PFS (P = 0.954) and OS (P = 0.880). Age≥70 years was an independent risk factor for OS of multiple primary early-stage lung cancer, according to an analysis of the prognostic variables of SBRT in 94 patients with multiple primary early-stage lung cancer. Regarding synchronous (≤180 d) and metachronous (>180 d) multiple primary early-stage lung cancer, there was no discernible difference between the two groups (P = 0.440). There was no significant difference in the total number of treatments for multiple primary early-stage lung cancer (P = 0.232) and no significant difference in the type of treatment for multiple primary early-stage lung cancer (P = 0.225) among 59 patients with synchronous multiple primary early-stage lung cancer within 5 years of the first-to-last treatment interval. Conclusion: SBRT has a strong and comparable efficacy for multiple primary early-stage lung cancer compared with single primary early-stage lung cancer, making it a viable treatment choice. Based on age and tumor biological behavior of the lesion, future strategies and procedures for local intervention of multiple primary early-stage lung cancer need to be investigated.

Background:The outcomes of locally advanced non-small cell lung cancer (LA-NSCLC) are unfavorable mainly due to a high risk of cancer recurrence. Only around 5% of patients can benefit from perioperative chemotherapy which is the current standard treatment. Recently, promising results with neoadjuvant targeted and immune-therapy therapy have been seen. However, most clinical trials are looking for patients eligible for certain drugs, instead of seeking suitable treatments for certain patients. Therefore, it is necessary to look for more efficient perioperative therapies to increase resectability, reduce recurrence and improve prognosis.Methods/Design:The study is an open-label, prospective, phase II, umbrella trial, enrolling patients diagnosed with treatment-naïve potentially resectable Stage II-IIIB NSCLC. Next-generation sequencing (NGS) using a 68-gene panel is performed for biopsies of tumor tissues from eligible patients. Enrolled patients are then stratified into six independent cohorts based on the status of gene mutations and PD-L1 status in tumor tissues, that is, ①EGFR 19del group, ②EGFR 21 L858R group, ③EGFR rare mutation group, ④Other driver mutation group, ⑤Drive mutation-negative group with PD-L1≥1%, ⑥Drive mutation-negative group with PD-L1<1%. A Simon's two-stage design is performed in each cohort independently and patients receive corresponding standard therapies accordingly. We aim to enroll 26 patients in each cohort and totally 156 patients will be enrolled. The primary endpoint is objective response rate (ORR). Secondary endpoints include oncological prognosis and perioperative outcomes. Exploratory endpoint is to investigate patient-specific minimal residual disease (MRD) in predicting treatment efficacy and oncological prognosis.Discussions:This is the first umbrella trial focusing on the safety and efficacy of precise neoadjuvant therapy for patients diagnosed with potentially resectable LA-NSCLC based on NGS results. The results of this trial would help improve overall treatment results in LA-NSCLC patients.Trial registration:Chinese Clinical Trial Registry. Trial registration number: ChiCTR2100053021.Advantages and limitations of this study:There is no neoadjuvant umbrella trial focusing on LA-NSCLCs. This is the first neoadjuvant umbrella trial, using a precise individualized approach and seeking suitable drugs for LA-NSCLC patients, with the aim to improve overall treatment outcomes.Clinical trial registration:https://www.chictr.org.cn/, identifier ChiCTR2100053021.

Objectives: The prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis.Methods: The phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or sur-gery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy.Results: In total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recur-rence versus recurrence-free (17.8% vs 89.2%; P <.001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locore-gional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence inter-val, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression sug-gested that NCRT, age >60 years, early recurrence, and the pN1 stage were inde-pendent risk factors for shortened survival after recurrence.Conclusions: Prerecurrence primary tumor stage is inaccurate in predicting post-recurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is asso-ciated with a worse prognosis in patients with recurrence, especially early recur-rence. (J Thorac Cardiovasc Surg 2023;165:888-97)

PURPOSE:To identify the valuable predictors of grade≥2 radiation pneumonitis (RP) in patient treated with radiotherapy after pneumonectomy for non-small cell lung cancer (NSCLC); and to construct a nomogram predicting the incidence of grade≥2 RP in such patients. PATIENTS AND METHODS:We reviewed 82 patients with NSCLC received radiotherapy after pneumonectomy from 2008 to 2018. The endpoint was grade≥2 RP. Univariate and multivariate regression analysis were conducted to evaluate significant factors of grade≥2 RP. Receiver operating characteristic (ROC) curve was used to establish optimal cutoff values and the nomogram was built to make the predictive model visualized. Descriptive analysis was performed on 5 patients with grade 3 RP. RESULTS:A total of 22(26.8%) patients developed grade 2 RP and 5(6.1%) patients were grade 3 RP. V5, V10, V20, V30, MLD, PTV, and PTV/TLV were associated with the occurrence of grade≥2 RP in univariate analysis, while none of the clinical factors was significant; V5(OR,1.213;95%CI,1.099-1.339; P<0.001) and V20(OR,1.435;95%CI,1.166-1.765; P=0.001) were the independent significant predictors by multivariate analysis and were included in the nomogram. The ROC analysis for the cutoff values for predicting grade≥2 RP were V5>23% (AUC=0.819, sensitivity:0.701, specificity:0.832) and V20>8% (AUC=0.812, sensitivity:0.683, specificity:0.811). Additionally, grade≥3 RP did not occur when V5<30%, V20<13% and MLD<751.2cGy, respectively. CONCLUSIONS:Our study showed that V5 and V20 were independent predictors for grade≥2 RP in NSCLC patients receiving radiotherapy after pneumonectomy. Grade 3 RP did not occur whenV5<30%, V20<13% and MLD<751.2cGy, respectively. In addition, patient underwent right pneumonectomy may have a lower tolerance to radiation compared to left pneumonectomy.

Background: Few studies have exclusively investigated the value of pathological complete response (pCR), in esophageal squamous cell carcinoma (ESCC) patients, although it is a clinically significant parameter to evaluate the impact of neoadjuvant chemoradiotherapy (nCRT) on treatment outcome after surgery. The aim of our study was to explore the relationship between pCR after nCRT and survival among patients with local ESCC. Methods: All patients receiving nCRT followed by surgery in NEOCRTEC5010-trial (NCT01216527) were included. Non-pCR patients were classified into three subgroups: ypTanyN0M0, ypT0NanyM0 and ypTanyNanyM0. The Kaplan-Meier method with log-rank test was employed to evaluate disease-free survival (DFS) and overall survival (OS). Multivariate regression analysis was performed using a Cox proportional hazards model to identify clinicopathological parameters associated with pCR. Results: Among the 185 patients included, 80 (43.2%) achieved pCR after nCRT. The mean survival time of the pCR group was significantly longer than that of the non-pCR group (92.6 vs. 69.2 months; HR, 2.70; 95% CI, 1.48-4.92; P=0.001). The 5-year OS and DFS of the pCR group were 79.3% and 77% respectively, compared to 54.8% and 51.2%, respectively, in the non-pCR group. The results showed that the OS and DFS of the ypTanyN0M0 group were better than those of the ypT0NanyM0 group and the ypTanyNanyM0 group. We also found that the number of dissected lymph nodes and pCR were independent risk factors for DFS and OS rates. Conclusions: pCR after nCRT is an important prognostic indicator of OS and DFS in patients with ESCC. In addition, lymph-node status could represent an important parameter in the prognostic evaluation of esophageal cancer patients.

Objectives: This study aimed to evaluate the effect of postoperative radiotherapy (PORT) in patients with resected pathologic N2 (pN2) non-small cell lung cancer (NSCLC) with different locoregional recurrence (LRR) risks. Materials and methods: The primary cohort and validation cohort were retrieved from two independent medical centres. Data for all consecutive patients with completely resected pathologic stage T1-3N2M0 NSCLC were analysed. Patients without PORT in the primary cohort were identified as a training set. Significant prognostic factors for LRR were identified by the Fine-Gray model to develop a prognostic index (PI) in the training set. Results: The primary cohort consisted of 357 patients who met the eligibility criteria (training set, 287 patients without PORT). The external validation cohort consisted of 1044 patients who met the eligibility criteria (validation set, 711 patients without PORT). Heavy cigarette smoking history, clinical N2 status (cN2), and the number of positive lymph nodes >4 were identified as independent risk factors. The PI was computed as follows: PI=0.8*smoking history+0.5*cN2+0.7*the number of involved lymph nodes (reference level was assigned the value 1 and risk level the value 2). In the low-risk group (PI score< = 3), PORT showed a trend towards decreased LRR rates but not significantly improved overall survival (OS). In the high-risk group (PI score>3), PORT significantly reduced the risk of LRR and improved OS. Conclusions: We constructed and validated a PI to predict individually the effect of PORT in patients with completely resected pN2 NSCLC. Patients with a higher PI score can benefit from PORT in terms of OS.

Objective: To clarify whether systemic LND influences the safety of surgery and the survival of patients with locally advanced esophageal squamous cell carcinoma (ESCC) after neoadjuvant chemoradiotherapy (nCRT). Summary of Background Data: Prognostic impact of systemic lymphadenectomy during surgery after nCRT for ESCC is still uncertain and requires clarification. Methods: This is a secondary analysis of NEOCRTEC5010 trial which compared nCRT followed by surgery versus surgery alone for locally advanced ESCC. Relationship between number of LND and perioperative, recurrence, and survival outcomes were analyzed in the nCRT group. Results: Three-year overall survival was significantly better in the nCRT group than the S group (75.2% vs 61.5%; P = 0.011). In the nCRT group, greater number of LND was associated with significantly better overall survival (hazard ratio, 0.358; P < 0.001) and disease-free survival (hazard ratio, 0.415; P = 0.001), but without any negative impact on postoperative complications. Less LND (<20 vs ≥20) was significantly associated with increased local recurrence (18.8% vs 5.2%, P = 0.004) and total recurrence rates (41.2% vs 25.8%, P = 0.027). Compared to patients with persistent nodal disease, significantly better survival was seen in patients with complete response and with LND ≥20, but not in those with LND <20. Conclusions: Systemic LND does not increase surgical risks after nCRT in ESCC patients. And it is associated with better survival and local disease control. Therefore, systemic lymphadenectomy should still be considered as an integrated part of surgery after nCRT for ESCC.

The aim of this study is to evaluate fertility preservation (FP) popularization in China among female cancer patients in terms of awareness of fertility, knowledge about FP, and attitudes toward FP. A questionnaire-based survey was conducted among female cancer patients in Tongji Hospital in China from March 2019 to July 2019. The 29 fertility-related issues, which were presented in either five-point Likert scales or "yes or no", in this questionnaire consisted of demographic characteristic and disease-related situation, awareness of fertility, knowledge about FP, and attitudes toward FP. Participants were required to finish the questionnaire, and data were gathered and analyzed by SPSS. Forty-five valid questionnaires without missing data remained in the final analysis. The survey discovered that a regional imbalanced limitation in knowledge of infertility risk and FP in young cancer patients acted as a major obstacle in FP promotion nationwide and FP decision-making in patients. Compared with rural patients, patients from urban areas were more eager to give birth and more likely to have a better understanding of FP with a more positive attitude. Moreover, most of the participants (62.2%) had a low level of understanding of FP, although they remained positive toward it. "Cancer treatment as the priority", "Cancer relapse caused by FP", and "Health of the next generation" were the top three factors affecting decisions on FP. The findings revealed a general FP actuality in China and specifically offered some intervention targets in the near future to improve FP service and networks, benefiting more female patients of childbearing age who are at risk of infertility.

PURPOSE:This study aimed to evaluate the efficacy and safety of intensity modulated radiation therapy (IMRT) for pleural recurrence of thymoma that was not suitable for surgery and had progressed after chemotherapy.MATERIALS AND METHODS:From February 2012, consecutive patients with pleural recurrence of thymoma were prospectively enrolled. Due to dose restrictions to normal tissue (lung, liver, and kidney), 3 different levels of radiation doses (30 Gy, 40 Gy, and 50 Gy) were prescribed for pleural lesions of different sizes and locations, with a daily fraction dose of 2 Gy. The objective response rate, local control time (LCT), overall survival time, and toxicity were recorded, respectively.RESULTS:By August 2016, 31 patients had completed the IMRT treatment. There were 21 male and 10 female patients, with a median age of 49 (range, 22-70) years. B3 thymoma was the major (62%) tumor subtype observed. During the median follow-up of 48 (24-70) months, the objective response rate was 97%, and the median LCT was 49 (95% confidence interval, 40.4-58.1) months. However, 29 (93.5%) patients developed out-of-field recurrence, among whom 10 (32%; 30 Gy, n = 7; 40 Gy, n = 3) developed both out-of-field and in-field recurrence. The median progression-free survival was 19 months, and no in-field recurrence occurred in the 50 Gy group. Moreover, a higher dose was related to a longer LCT. No toxicities higher than a grade 4 occurred after IMRT within the normal-tissue dose limitation. The 5-year overall survival of the patients was 81%.CONCLUSIONS:IMRT for pleural recurrence may act as an alternative treatment when surgery is not feasible, with a higher dose resulting in a longer LCT. In this study, out-of-field recurrence was considerably common, but repeated IMRT for new recurrence should be cautiously carried out due to the high risk of radiation-induced pneumonitis.

BACKGROUND:The study aimed to evaluate the role of postoperative radiotherapy (PORT) in the treatment of trachea and main bronchus adenoid cystic carcinoma (ACC) with a positive surgical margin. METHODS:Patients with pathologically confirmed trachea or main bronchus ACC operated on at Shanghai Chest Hospital were enrolled. Survival, univariate, and multivariate analyses were performed. The χ2 test was applied to analyze the failure patterns among different groups (R0/0: negative margin resection without PORT; R1/0: positive margin resection without PORT; R1/1: positive margin resection with PORT). RESULTS:From January 2001 to December 2014, 77 patients were deemed eligible for the study. Pairwise comparisons showed that the overall survival rate of group R1/1 was comparable to that of group R0/0 (P = .438), and significantly longer than the rate of group R1/0 (P = .032). Additionally, the local disease-free survival rate of group R1/1 was much higher than that of group R0/0 (P = .023) and R1/0 (P = .001). Cox multivariate analysis identified the radiologic feature (P = .012) and PORT (P = .006) as significantly favorable prognostic factors for locoregional disease-free survival. By contrast, for overall survival, PORT (P = .032) was the only corresponding variable identified by univariate analysis. Furthermore, PORT significantly decreased the locoregional recurrence rate (P = .002) but not distant metastases (P > .999). CONCLUSIONS:PORT helped patients with tracheobronchial ACC and microscopic positive surgical margins to achieve a similar outcome as patients with complete resection. R0 resection may not be necessary for tracheobronchial ACC if it is difficult to be completely resected.

Background: Inflammation plays a vital role in tumor growth and progression and can be affected by radiotherapy (RT) and chemotherapy. We sought to investigate the prognostic significance of neutrophilto-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), and their associations with dosimetric factors in locally advanced non-small cell lung cancer (LA-NSCLC). Methods: In this retrospective study, subjects consisted of 244 patients who had received definitive RT +/- chemotherapy for LA-NSCLC between 2012 and 2016. Absolute lymphocyte count (ALC), NLR and PLR recorded at pretreatment, during RT and post-RT were analyzed. Multivariable analysis (MVA) was performed to correlate clinical factors and inflammatory biomarkers with progression-free survival (PFS) and overall survival (OS) using a Cox regression model. Relationships between NLR or PLR with OS and PFS were evaluated with Kaplan-Meier analysis and compared with log-rank test results. Multiple stepwise linear regression was used to assess the associations between dosimetric factors and NLR or PLR. Results: The median PFS and OS for all patients were 8.6 and 15.8 months, respectively. On MVA for PFS and OS, higher 1-month post-RT start NLR [hazard ratio (HR) 1.049; 95% CI: 1.018-1.080; P=0.001] or higher 1-month post-RT start PLR (HR 1.001; 95% CI: 1.000-1.002; P<0.001) was associated with inferior PFS. Higher 1-month post-RT start NLR (HR 1.040; 95% CI: 1.013-1.069; P=0.004) or PLR (HR 1.001; 95% CI: 1.001-1.002; P< 0.001) was also an independent predictor of OS. ALCmin, baseline NLR and PLR were not associated with treatment outcomes. Multiple stepwise linear regression analysis confirmed that baseline NLR (P<0.001), heart V20 (P<0.001), heart V40 (P<0.001), and mean body dose (MBD) were significantly associated with 1-month post-RT start NLR. Also, baseline PLR (P<0.001) and MBD (P<0.001) were significantly associated with 1-month post-RT start PLR. Conclusions: Higher NLR and PLR during treatment were associated with worse patient outcomes, and heart dose or body dose was correlated with NLR or PLR in advanced NSCLC patients treated with definitive RT.

OBJECTIVE:To determine the prognostic impact of pathologic lymph node (LN) status and investigate risk factors of recurrence in esophageal squamous cell carcinoma (ESCC) patients with pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (NCRT).SUMMARY BACKGROUND DATA:There are no large-scale prospective study data regarding ypN status and recurrence after pCR in ESCC patients receiving NCRT.METHODS:The NEOCRTEC5010 trial was a prospective multicenter trial that compared the survival and safety of NCRT plus surgery (S) with S in patients with locally advanced ESCC. The relationships between survival and cN, pN, and ypN status were assessed. Potential prognostic factors in patients with ypN+ and pCR were identified.RESULTS:A total of 389 ESCC patients (NCRT: 182; S: 207) were included. Patients with pN+ in the S group and ypN+ in the NCRT group had decreased overall survival (OS) and disease-free survival (DFS) compared with pN0 and ypN0 patients, respectively. Partial response at the primary site [hazard ratio (HR), 2.09] and stable disease in the LNs (HR, 3.26) were independent risk factors for lower DFS, but not OS. For patients with pCR, the recurrence rate was 13.9%. Patients with distant LN metastasis had a median OS and DFS of 16.1 months and 14.4 months, respectively. Failure to achieve the median total dose of chemotherapy was a significant risk factor of recurrence and metastasis after pCR (HR, 44.27).CONCLUSIONS:Persistent pathologic LN metastasis after NCRT is a strong poor prognostic factor in ESCC. Additionally, pCR does not guarantee a cure; patients with pCR should undergo an active strategy of surveillance and adjuvant therapy.

BACKGROUND There has been no study comparing the difference in the failure patterns between patients with or without postoperative radiotherapy (PORT) after esophagectomy for pT3-4N0-3M0 esophageal squamous cell carcinoma (ESCC). AIM To investigate the difference in the failure patterns of stage pT3-4N0-3M0 ESCC patients with or without PORT. METHODS Patients with stage pT3-4N0-3M0 ESCC, who underwent surgery with or without PORT, were enrolled in this study. The primary endpoint was to investigate the difference in the failure patterns between patients with or without PORT after esophagectomy. The secondary endpoint was to estimate whether patients with stage pT3-4 ESCC could achieve a disease-free survival (DFS) advantage after receiving adjuvant PORT. Statistical analyses were performed by the Kaplan-Meier method, Cox regression model, and Chi-squared test or Fisher’s exact test. RESULTS In total, 230 patients with stage pT3-4N0-3M0 ESCC were included in this study. Fifty-six patients who received PORT were screened from a prospective cohort (S + R arm). And 174 patients involving surgery alone were retrospectively selected from July 2006 to October 2014 (S arm). There were no significant differences in the clinical or pathological characteristics of patients between the two arms, except for tumor location (P = 0.031). The failure patterns between the two arms were significantly different (P < 0.001). Patients in the S arm had a significantly higher proportion of locoregional recurrence and a lower proportion of distant metastasis than those in the S + R arm (92.0% vs 35.7%, P < 0.001 and 19.0% vs 75.0%, P < 0.001, respectively). The difference in the median DFS between the two arms was statistically significant (12.7 vs 8 mo, P = 0.048). Univariate analysis and multivariate analysis both demonstrated that the number of lymph node metastases ≥ 3 (HR = 0.572, 95%CI: 0.430-0.762, P < 0.001) was an independent poor prognostic factor for DFS in patients with stage pT3-4N0-3M0 ESCC. CONCLUSION PORT could improve DFS and local control of patients with stage pT3-4N0-3M0 ESCC. However, further studies need to be conducted to control hematogenous metastasis after PORT.

BACKGROUND:Combined small cell lung cancer (C-SCLC) is defined as small cell lung cancer (SCLC) combined with any of non-small cell lung cancer (NSCLC) histological types, such as large cell carcinoma, squamous cell carcinoma, or adenocarcinoma. Since C-SCLC is an increasingly recognized subtype of small cell carcinoma, we conducted a retrospective study in our institution to explore the value of prophylactic cranial irradiation (PCI) in patients with C-SCLC treated by surgery.METHODS:Between 2005 and 2014, the records of all consecutive patients with pathologically diagnosed C-SCLC after surgery in our institution were reviewed. Overall survival (OS), disease-free survival (DFS), and brain metastasis free survival (BMFS) were estimated by Kaplan-Meier method. Survival differences were evaluated by log-rank test, while multivariate analysis was performed by a Cox proportional hazards model.RESULTS:Of the total 91 patients included in this analysis, 11 patients (12.1%) were in PCI group and 80 (87.9%) in non-PCI group. The 5-year cumulative incidence of brain metastasis in the whole group was 22.2% (26.3% in non-PCI group vs. 0% in PCI group), and 5-year OS rate was 44.1%. Patients treated with PCI had significantly longer OS (P=0.011) and DFS (P=0.013), also had the trend to live a longer BMFS with marginal significance (P=0.092) than non-PCI-treated patients. The multivariate analysis showed that PCI [hazard ratio (HR) =0.102, P=0.024] was one of independent prognostic factors of the OS in surgery-treated C-SCLC patients.CONCLUSIONS:C-SCLC patients have a relative high risk of developing brain metastases based on our study. These data showed that PCI could improve OS and DFS, as well as tend to decrease brain metastases in surgically resected C-SCLC. However, whether PCI could be part of comprehensive treatment modalities in C-SCLC should be assessed in prospective studies.