Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study.

BACKGROUND: Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS: A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION: Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.

A nomogram to predict the cumulative risk for brain metastases in patients with limited-stage small cell lung cancer without prophylactic cranial irradiation.

OBJECTIVE: Patients with small cell lung cancer (SCLC) have a high risk of developing brain metastases (BM). Prophylactic cranial irradiation (PCI) is a standard therapy for limited-stage SCLC (LS-SCLC) patients who achieved complete or partial response after thoracic chemoradiotherapy (Chemo-RT). Recent studies have indicated that a subgroup of patients with a lower risk of BM can avoid PCI, and the present study therefore tries to construct a nomogram to predict the cumulative risk of development of BM in LS-SCLC patients without PCI. METHODS: After screening of 2298 SCLC patients who were treated at the Zhejiang Cancer Hospital from December 2009 to April 2016, a total of 167 consecutive patients with LS-SCLC who received thoracic Chemo-RT without PCI were retrospectively analyzed. The paper analyzed clinical and laboratory factors that may be correlated with BM, such as response to treatment, pretreatment serum neuron-specific enolase (NSE) and lactate dehydrogenase (LDH) levels, and TNM stage. Thereafter, a nomogram was constructed to predict 3­ and 5­year intracranial progression-free survival (IPFS). RESULTS: Of 167 patients with LS-SCLC, 50 developed subsequent BM. Univariate analysis showed that pretreatment LDH (pre-LDH) ≥ 200 IU/L, an incomplete response to initial chemoradiation, and UICC stage III were positively correlated to a higher risk of BM (p < 0.05). Multivariate analysis identified pretreatment LDH level (hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.08-3.34, p = 0.026), response to chemoradiation (HR 1.87, 95% CI 1.04-3.34, p = 0.035), and UICC stage (HR 6.67, 95% CI 1.03-49.15, p = 0.043) as independent predictors for the development of BM. A nomogram model was then established, and areas under the curve of 3­year and 5­year IPFS were 0.72 and 0.67, respectively. CONCLUSION: The present study has developed an innovative tool that is able to predict the individual cumulative risk for development of BM in LS-SCLC patients without PCI, which is beneficial for providing personalized risk estimates and facilitating the decision to perform PCI.

Using clinical and radiomic feature-based machine learning models to predict pathological complete response in patients with esophageal squamous cell carcinoma receiving neoadjuvant chemoradiation.

OBJECTIVE: This study aimed to build radiomic feature-based machine learning models to predict pathological clinical response (pCR) of neoadjuvant chemoradiation therapy (nCRT) for esophageal squamous cell carcinoma (ESCC) patients. METHODS: A total of 112 ESCC patients who underwent nCRT followed by surgical treatment from January 2008 to December 2018 were recruited. According to pCR status (no visible cancer cells in primary cancer lesion), patients were categorized into primary cancer lesion pCR (ppCR) group (N = 65) and non-ppCR group (N = 47). Patients were also categorized into total pCR (tpCR) group (N = 48) and non-tpCR group (N = 64) according to tpCR status (no visible cancer cells in primary cancer lesion or lymph nodes). Radiomic features of pretreatment CT images were extracted, feature selection was performed, machine learning models were trained to predict ppCR and tpCR, respectively. RESULTS: A total of 620 radiomic features were extracted. For ppCR prediction models, radiomic model had an area under the curve (AUC) of 0.817 (95% CI: 0.732-0.896) in the testing set; and the combination model that included rad-score and clinical features had a great predicting performance, with an AUC of 0.891 (95% CI: 0.823-0.950) in the testing set. For tpCR prediction models, radiomic model had an AUC of 0.713 (95% CI: 0.613-0.808) in the testing set; and the combination model also had a great predicting performance, with an AUC of 0.814 (95% CI: 0.728-0.881) in the testing set. CONCLUSION: This study built machine learning models for predicting ppCR and tpCR of ESCC patients with favorable predicting performance respectively, which aided treatment plan optimization. CLINICAL RELEVANCE STATEMENT: This study significantly improved the predictive value of machine learning models based on radiomic features to accurately predict response to therapy of esophageal squamous cell carcinoma patients after neoadjuvant chemoradiation therapy, providing guidance for further treatment. KEY POINTS: • Combination model that included rad-score and clinical features had a great predicting performance. • Primary tumor pCR predicting models exhibit better predicting performance compared to corresponding total pCR predicting models.

A research on the improved rotational robustness for thoracic organ delineation by using joint learning of segmenting spatially-correlated organs: A U-net based comparison.

PURPOSE: To study the improved rotational robustness by using joint learning of spatially-correlated organ segmentation (SCOS) for thoracic organ delineation. The network structure is not our point. METHODS: The SCOS was implemented in a U-net-like model (abbr. SCOS-net) and evaluated on unseen rotated test sets. Two hundred sixty-seven patients with thoracic tumors (232 without rotation and 35 with rotation) were enrolled. The training and validation images came from 61 randomly chosen unrotated patients. The test data included two sets. One consisted of 3000 slices from the rest 171 unrotated patients. They were rotated by us by -30°âˆ¼30°. One was the images from the 35 rotated patients. The lung, heart, and spinal cord were delineated by experienced radiation oncologists and regarded as ground truth. The SCOS-net was compared with its single-task learning counterparts, two published multiple learning task settings, and rotation augmentation. Dice, 3 distance metrics (maximum and 95th percentile of Hausdorff distances and average surface distance (ASD)) and the number of cases where ASD = infinity were adopted. We analyzed the results using visualization techniques. RESULTS: In terms of no augmentation, the SCOS-net achieves the best lung and spinal cord segmentations and comparable heart delineation. With augmentation, SCOS performs better in some cases. CONCLUSION: The proposed SCOS can improve rotational robustness, and is promising in clinical applications for its low network capacity and computational cost.

Apatinib in patients with recurrent or metastatic thymic epithelial tumor: a single-arm, multicenter, open-label, phase II trial.

BACKGROUND: Thymic epithelial tumors (TETs) are rare malignancies and the treatment options are limited. We aimed to evaluate the efficacy and safety of apatinib, an angiogenesis inhibitor, in advanced TETs. METHODS: This was an open-label, single-arm, phase II trial at three centers in China. Patients with TET who had progressed after failure of at least one line of platinum-based chemotherapy were enrolled. Patients received apatinib 500 mg orally per day. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. RESULTS: From June 29, 2017, to April 18, 2019, 25 patients were enrolled. At data cut off (September 30, 2021), one patient achieved complete response, nine achieved partial response, and 11 achieved stable disease, with an ORR of 40% (95% CI 21-61%) and DCR of 84% (95% CI 64-95%). The median PFS was 9.0 (95% CI 5.4-12.6) months. The median OS was 24.0 (95% CI 8.2-39.8) months. All patients reported treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred 26 times in 15 patients. No grade 4 or 5 toxicities occurred. CONCLUSIONS: This is the first trial of apatinib for the treatment of TETs. Apatinib showed promising antitumor activity and the toxicities were tolerable and manageable.

Serum lactate dehydrogenase predicts brain metastasis and survival in limited-stage small cell lung cancer patients treated with thoracic radiotherapy and prophylactic cranial irradiation.

BACKGROUND: Small cell lung cancer (SCLC) is characterized by a high risk of brain metastasis and poor survival. This study aims to assess the prognostic role of lactate dehydrogenase (LDH) in limited-stage small cell lung cancer (LS-SCLC) treated with thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI). METHODS: This study retrospectively evaluated 197 consecutive patients who underwent TRT and PCI for LS-SCLC between November 2005 and October 2017. Both pretreatment and maximal serum LDH levels (mLDH) during treatment were checked, and an increased LDH level was defined as more than 240 IU/ml. Clinical factors were tested for associations with intracranial progression-free survival (IPFS) and overall survival (OS) after PCI. The Kaplan-Meier method was used to calculate survival rates, and multivariate Cox regression analyses were carried out to identify variables associated with survival. RESULTS: Of the total patients, 28 had higher pretreatment LDH levels and mLDH levels were increased in 95 patients during treatment. In patients in the normal and elevated mLDH groups, the 1­, 2­, and 5­year IPFS rates were 96.7% vs. 90.1%, 91.7% vs. 73.8%, and 87.8% vs. 61.0% (P < 0.01), respectively. Compared to those with normal LDH levels, patients with increased mLDH levels had a higher cumulative risk of intracranial metastasis (hazard ratio [HR] 3.87; 95% confidence interval [CI] 1.73-8.63; P < 0.01) and worse overall survival (HR 2.59; 95% CI 1.67-4.04; P < 0.01). The factors LDH level at baseline or changes between pretreatment level and maximum level during treatment failed to predict brain metastases or OS with statistical significance. In the multivariate analyses, both mLDH during treatment (HR 3.53; 95% CI 1.57-7.92; P = 0.002) and patient age ≥ 60 (HR 2.46; 95% CI 1.22-4.94; P = 0.012) were independently associated with worse IPFS. Factors significantly associated with worse OS included mLDH during treatment (HR 2.45; 95% CI 1.56-3.86; P < 0.001), IIIB stage (HR 1.75; 95% CI 1.06-2.88; P = 0.029), and conventional radiotherapy applied in TRT (HR 1.66; 95% CI 1.04-2.65; P = 0.034). CONCLUSION: The mLDH level during treatment predicts brain metastasis and survival in LS-SCLC patients treated with TRT and PCI, which may provide valuable information for identifying patients with poor survival outcomes and possible candidates for treatment intensification.

Psychological distress of cancer patients caused by treatment delay during the COVID-19 pandemic in China: A cross-sectional study.

OBJECTIVE: The currents study sought to explore the impact of treatment delay on the mental health for patients with cancer during the 2019 coronavirus disease (COVID-19) pandemic. METHODS: Travel restrictions were imposed in most areas of the country between 23 January 2020 and 25 February 2020 owing to the COVID-19 epidemic. Travel restrictions were lifted from 26 February 2020 to 12 March 2020. The number of new confirmed cases significantly reduced after 12 March 2020. Study participants, comprised of individuals from three distinct groups: (1) 835 cancer patients who attended Zhejiang Cancer Hospital between 26 February 2020 and 12 March 2020; (2) 185 healthy volunteers recruited between 26 February 2020 and 12 March 2020; (3) 168 cancer patients who attended the hospital during the non-epidemic period (after 12 March 2020). Two outcome measures including patients' posttraumatic stress responses and general psychological distress (GPD) were assessed using the Chinese versions of the Impact of Events Scale-Revised and the Kessler Psychological Distress Scale (K10). Treatment delay was assessed via counting the time interval from diagnosis to treatment initiation, or from planned treatment date to actual date of therapy. Communication satisfaction was evaluated via a self-report questionnaire. An independent sample t-test or Wilcoxon rank sum test was used for comparison. Statistical analysis included Chi-square test, Mann-Whitney test and multivariate logistic regression. RESULTS: All 1188 participants (835 patients with cancer and 185 controls during the outbreak, and 168 patients with cancer during the non-epidemic period) completed and submitted the questionnaires. A positive association was observed between treatment delays and increased GPD levels (OR 1.716; 95% confidence interval ,CI 1.254-2.348; p = 0.001) as well as posttraumatic stress disorder (PTSD) symptoms (OR: 1.545, 95% CI: (1.166-2.047), p = 0.002). Patients who reported good communication with their doctors showed a significantly lower risk of GPD (OR: 0.526, 95% CI (0.348-0.794), p = 0.002) and PTSD (OR: 0.683, 95% CI (0.490-0.951), p = 0.024) compared with patients who reported unsatisfactory communication or had no contact with their doctors. Multivariate logistic regression analysis showed that treatment at a local hospital, treatment delays and unsatisfactory or no communication with cancer-care professionals were significantly correlated with severe GPD and PTSD symptoms of patients (all p ≤ 0.05). CONCLUSION: The findings indicate that cancer patients who underwent treatment delays during the COVID-19 pandemic may become vulnerable to psychological distress. The results showed that effective communication with doctors and cancer-care professionals during outbreak significantly reduces GPD levels and PTSD symptoms.

Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench.

BACKGROUND: Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC. METHODS: LDHA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan-Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and monodansylcadaverine (MDC) staining was used to examine cell autophagy. RESULTS: Both mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity. CONCLUSIONS: Our study suggests that inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.

Elevated platelet count is a strong predictor of poor prognosis in stage I non-small cell lung cancer patients.

Stage I non-small cell lung cancer (NSCLC) show a highly variable biological behavior which cannot be accurately predicted by the current available prognostic markers. Platelet plays a significant role in cancer cell growth, progression and metastasis. This study aimed to investigate whether preoperative platelet count correlate with clinical prognosis in localized NSCLC. A retrospective clinical analysis was designed for a total of 234 stage I NSCLC patients in our hospital between October 2006 and December 2009. Pre-operative platelet count was measured. The association of platelet count with clinical pathological factors and patient outcome was evaluated. A significant correlation was detected between platelet count and tumor cell differentiation and T stage. Patients with elevated platelet count had an elevated risk of disease progression and death compared to patients with normal platelet count. The hazard ratio was 5.314 (95% confidence interval [CI] 2.750-10.269) for disease progression and 3.139 (95% CI 1.227-8.034) for death. The trend linking increasing platelet count with risk was also statistically significant for both the outcomes (p < 0.05). These finding demonstrate that preoperative platelet count is a useful predictor of high risk progression and poor prognosis in stage I NSCLC patients.

Correlation of NAT10 expression with clinical data and survival profiles in esophageal squamous cell carcinoma patients, and its impact on cell proliferation and apoptosis.

BACKGROUND: This study investigates the association between NAT10 expression and clinical parameters while assessing prognostic outcomes in esophageal squamous cell carcinoma (ESCC) patients. Furthermore, the study seeks to elucidate the functional role of NAT10 in neoplastic cell proliferation and apoptosis. MATERIALS AND METHODS: NAT10 expression was assessed in ESCC tissue microarrays through immunohistochemistry (IHC) tests. We employed SPSS software to analyze the correlation between NAT10 staining data, clinical indicators, and their implications for patient prognosis. Small interference RNA (siRNA) was utilized to inhibit NAT10 expression in two esophageal cancer cell lines, TE-1 and KYSE150. Subsequently, we meticulously quantified and compared cellular proliferation and apoptotic ratios among experimental groups. NAT10, Ki67, and Caspase3 expression levels in different groups were evaluated using quantitative polymerase chain reaction (qPCR) and Western blot (WB) assays. Statistical analyses were conducted using GraphPad Prism software, with significance at p<0.05. RESULTS: Our findings indicate that NAT10 is overexpressed in ESCC tissues and exhibits a significant correlation with tumor diameter and overall patient survival. Decreasing NAT10 expression led to the inhibition of tumor cell proliferation and the promotion of apoptosis. Furthermore, siRNA-mediated NAT10 inhibition resulted in the downregulation of Ki67 expression and the concomitant upregulation of Caspase3. CONCLUSION: The observed overexpression of NAT10 in ESCC tissues is associated with larger tumor diameters and reduced patient survival. NAT10 appears to play a pivotal role in the progression of esophageal cancer by influencing cell proliferation and apoptosis. These findings suggest potential clinical implications, with Ki67 and Caspase3 potentially participating in this intricate molecular biological process.

Qingfei mixture modulates the immune responses in lung cancer through modulating mTOR signaling and gut microbiota-derived short-chain fatty acids.

Lung cancer ranks among the primary contributors to cancer-related fatalities on a global scale. Multiple research investigations have demonstrated that there exists a dysbiosis within the intestinal bacteria and short-chain fatty acids (SCFAs) is linked with immune responses in lung cancer. Qingfei mixture (QFM) has been widely used in treating lung cancer, yet the active ingredients and roles of the QFM on immune responses by targeting gut microbiota remain to be elucidated. The chemical constituents of QFM were qualitatively examined by UPLC/Q-TOF-MS. Additionally, we evaluated the therapeutic impact of the organic substance QFM on lung cancer, aiming to elucidate its mechanisms for improving the tumor-immune microenvironment. Herein, we constructed a Lewis lung carcinoma (LLC)-bearing mice model with QFM treatment to observe tumor growth and immune cell changes. Then, the feces were collected and a combinatory study using metagenomes, non-targeted metabonomics, and targeted metabonomics of SCFAs was performed. In vitro experiments have been conducted to estimate the roles of acetate and sodium propionate in CD8+ T cells. Furthermore, we treated tumor-bearing mice with QFM, QFM + MHY1485 (an mTOR activator), and QFM + an antibiotic mixture (ABX) to explore the potential therapeutic benefit of regulation of the tumor microenvironment. A total of 96 compounds were obtained from QFM by UPLC/Q-TOF-MS. Besides, the findings demonstrated that QFM exhibited significant efficacy against lung cancer, manifesting in reduced tumor growth and improved immune responses. In investigating its mechanisms, we integrated gut microbiota sequencing and fecal metabolomics, revealing that QFM effectively restored disruptions in gut microbiota and SCFAs in mice with lung cancer. QFM, acetate, or sodium propionate contributed to the up-regulation of IFN-γ, Gzms-B, perforin, IL-17, IL-6, IL-12, TNF-α expressions and decreased HDAC and IL-10 levels in vitro and in vivo. Moreover, MHY1485 and ABX weakened the effects of QFM on immunomodulation. Collectively, these results suggest that QFM may facilitate immune responses in the LLC-bearing mice via regulating the gut microbiota-derived SCFAs at least partially through targeting the mTOR signaling pathway.

Factors Affecting the Risk of Brain Metastasis in Limited-Stage Small Cell Lung Cancer After Prophylactic Cranial Irradiation.

Background: Prophylactic cranial irradiation (PCI) can reduce the risk of brain metastases (BM) and improve overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC) after partial or complete response to primary therapy. However, some SCLC patients still develop BM after PCI. This study aimed to evaluate the risk factors of BM in patients with LS-SCLC after PCI and identify characteristics of patients who may not benefit from PCI. Methods and Materials: We identified 550 patients with LS-SCLC who received chemoradiotherapy at Zhejiang Cancer Hospital between 2002 and 2017. All patients received PCI. Kaplan-Meier analyses and Cox regression analyses were used to identify factors affecting OS and brain metastasis-free survival (BMFS). Results: For this patient population, the median survival time was 27.9 months, and the 5-year OS rate was 31%. The median survival time was 24.9 months (95% CI: 22.6-27.2 months), and 30.2 months (95% CI: 24.2-36.3 months) in patients with or without BM (P = 0.000). The overall BM rate was 15.6% (86/550). The frequency of BM in patients with pathologic stages I, II, and III were 9.3% (4/43), 13.4% (7/52), and 16.5% (75/455). The patients with tumors ≥5 cm had an increased risk of BM (HR: 1.781, 95% CI: 1.044-3.039, P = 0.034) but not death (HR: 1.126, 95% CI: 0.925-1.663, P = 0.182). The median survival time among patients <60 years was significantly longer than patients ≥60 years (34.9 months vs 24.6 months, P = 0.001); however, the difference in the BM risk between the two groups was not statistically significant. Conclusion: PCI remains the standard of care for LS-SCLC patients who achieve complete or partial response after completion of chemoradiotherapy. However, patients with tumors ≥5 cm may have a higher risk of developing BM after PCI.

Treatment Patterns and Outcomes of Elderly Patients With Potentially Curable Esophageal Cancer.

OBJECTIVES: The proportion of elderly patients with esophageal cancer (EC) is increasing due to prolonged life expectancy and aging process. The aim of the study is to explore the optimal treatment strategy for elderly patients (aged ≥70 years) with locally advanced EC. METHODS: Eligible patients with cT2-4aNxM0 EC were identified in the Surveillance, Epidemiology, and End Results database from 2010 to 2016. Treatment patterns were divided into six groups: surgical resection (S), chemoradiotherapy (CRT), trimodality therapy (CRT+S), radiotherapy (RT), chemotherapy (CT), or observation with no treatment (Obs). Survival between groups was compared using the log-rank test, and the Cox proportional hazards model was used to identify factors associated with overall survival (OS). RESULTS: A total of 2917 patients with potentially curable EC were identified. Of all the patients included, 6.7%, 51.8%, 18.0%, 9.4% and 3.6%received S, CRT, CRT+S, RT, and CT, respectively, whereas 10.6% underwent Obs. The 3-year OS estimates were 30.2% (95% confidence interval [CI]: 23.5-38.9%), 25.4% (95% CI: 22.8-28.3%),44.3% (95% CI: 39.3-49.9%), 11.4% (95% CI: 7.7-17.0%), 16.1% (95% CI: 9.1-28.3%), and 5.6% (95% CI: 3.2-9.8%) for S, CRT, CRT+S RT, CT, and Obs (p<0.001), respectively. Overall, patents underwent CRT+S had the longest OS, compared to other treatment patterns, and the survival difference was not significant between patients receiving CRT and S (p=0.12) in the elderly population. However, the survival benefits of trimodality therapy over CRT gradually weakened with the increase in age, and became statistically non-significant for EC patients aged ≥80 years (p=0.35). Multivariate analysis showed that treatment patterns, age, sex, tumor grade, T stage, N stage, and marital status were significantly associated with OS. CONCLUSION: Generally, the use of trimodality therapy was associated with the longest OS, the survival benefits were comparable between CRT and S alone, and CRT was superior to RT or CT alone in elderly patients with curable EC. For patients intolerable to surgery or aged ≥80 years, definitive CRT should be considered as a preferable option.

Crosstalk between the gut microbiome and clinical response in locally advanced thoracic esophageal squamous cell carcinoma during neoadjuvant camrelizumab and chemotherapy.

Background: The gut microbiome is associated with the response to immunotherapy in a variety of advanced cancers. However, the influence of the gut microbiome on locally advanced esophageal squamous cell carcinoma (ESCC) during programmed cell death protein 1 (PD-1) antibody immunotherapy plus chemotherapy is not clearly demonstrated. To explore the crosstalk between the gut microbiome and clinical response in locally advanced thoracic ESCC during neoadjuvant camrelizumab and chemotherapy. Methods: Patients who were diagnosed with locally advanced thoracic ESCC and had not received treatment were enrolled. The treatment regimen was two cycles of camrelizumab combined with carboplatin and albumin paclitaxel before surgery. The research endpoints were pathological complete response (pCR) and major pathological response (MPR). Fecal samples were collected at three time points: before neoadjuvant therapy, after two cycles of neoadjuvant therapy, and after surgery. We performed 16S ribosomal ribonucleic acid (rRNA) V3-V4 sequencing of the gene amplicons of fecal samples, as well as bacterial diversity and differential abundance analyses. Results: A total of 46 patients were recruited, and 44, 42, and 35 fecal samples were collected at the three time points, respectively. Statistically significant differences were observed in the amplicon sequence variant (ASV)-level alpha diversity indices, including Chao1, Shannon, and Good's coverage, between the three time points. The non-pCR-enriched gut microbiota included Proteobacteria, Dialister, Aeromonadales, Pseudomonadales, Thermi, Deinococci, Moraxellaceae, Rhodocyclales, Rhodocyclaceae, and Acinetobacter. The non-MPR-enriched gut microbiota included Pseudomonadales and the mitochondria family. The MPR-enriched gut microbiota included the Barnesiellaceae, Pyramidobacter, Dethiosulfovibrionaceae, Odoribacteraceae, Butyricimonas, Prevotella, Barnesiella, and Odoribacter. Patients with ≥3 grade adverse events (AEs) exhibited enrichment in the Succiniclasticum, Nakamurella, Rhizobium, Granulicella, Phyllobacteriaceae, Pelagibacteraceae, Actinosynnemataceae, Aquirestis, Flavisolibacter, Chelativorans, Coxiellaceae Acidicapsa, Acidobacteriaceae, Lentzea, Staphylococcus, Plesiomonas, Dysgonomonas, Pseudonocardia, and Ellin6075. Conclusions: We found that the diversity of the gut microbiome declined after neoadjuvant PD-1 antibody immunotherapy plus chemotherapy and surgery. Patients with pCR had different types and proportions of gut microbiota before treatment compared to those without pCR. We also observed the difference between patients with or without ≥ grade 3 AEs. The taxonomic features of the gut microbiome are potential biomarkers that could predict the pathological response and AEs.

A combined predictive model based on radiomics features and clinical factors for disease progression in early-stage non-small cell lung cancer treated with stereotactic ablative radiotherapy.

Purpose: To accurately assess disease progression after Stereotactic Ablative Radiotherapy (SABR) of early-stage Non-Small Cell Lung Cancer (NSCLC), a combined predictive model based on pre-treatment CT radiomics features and clinical factors was established. Methods: This study retrospectively analyzed the data of 96 patients with early-stage NSCLC treated with SABR. Clinical factors included general information (e.g. gender, age, KPS, Charlson score, lung function, smoking status), pre-treatment lesion status (e.g. diameter, location, pathological type, T stage), radiation parameters (biological effective dose, BED), the type of peritumoral radiation-induced lung injury (RILI). Independent risk factors were screened by logistic regression analysis. Radiomics features were extracted from pre-treatment CT. The minimum Redundancy Maximum Relevance (mRMR) and the Least Absolute Shrinkage and Selection Operator (LASSO) were adopted for the dimensionality reduction and feature selection. According to the weight coefficient of the features, the Radscore was calculated, and the radiomics model was constructed. Multiple logistic regression analysis was applied to establish the combined model based on radiomics features and clinical factors. Receiver Operating Characteristic (ROC) curve, DeLong test, Hosmer-Lemeshow test, and Decision Curve Analysis (DCA) were used to evaluate the model's diagnostic efficiency and clinical practicability. Results: With the median follow-up of 59.1 months, 29 patients developed progression and 67 remained good controlled within two years. Among the clinical factors, the type of peritumoral RILI was the only independent risk factor for progression (P< 0.05). Eleven features were selected from 1781 features to construct a radiomics model. For predicting disease progression after SABR, the Area Under the Curve (AUC) of training and validation cohorts in the radiomics model was 0.88 (95%CI 0.80-0.96) and 0.80 (95%CI 0.62-0.98), and AUC of training and validation cohorts in the combined model were 0.88 (95%CI 0.81-0.96) and 0.81 (95%CI 0.62-0.99). Both the radiomics and the combined models have good prediction efficiency in the training and validation cohorts. Still, DeLong test shows that there is no difference between them. Conclusions: Compared with the clinical model, the radiomics model and the combined model can better predict the disease progression of early-stage NSCLC after SABR, which might contribute to individualized follow-up plans and treatment strategies.

Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial.

IMPORTANCE: Most older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed. OBJECTIVE: To evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer. DESIGN, SETTING, AND PARTICIPANTS: A randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021. INTERVENTIONS: Patients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone. MAIN OUTCOMES AND MEASURES: The primary end point was the 2-year overall survival rate using intention-to-treat analysis. RESULTS: Of the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group. CONCLUSIONS AND RELEVANCE: In this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02813967.

Comparison of radiotherapeutic management of operated breast cancer in 1999 and in 2006: a sampling survey on the southeast coast of China.

AIMS: To obtain a better understanding of the changes in radiotherapeutic management of breast cancer patients in the more developed areas of China over the past decade. METHODS: Four academic radiation therapy departments located on the Southeast Coast of China were selected for the study. The survey was conducted on female breast cancer patients who received radiotherapy in 1999 and 2006. The questionnaires were designed to determine the purposes of radiotherapy and to address the postoperative radiotherapy techniques used. The data for these two years were analyzed and compared. RESULTS: The percentage of breast-conserving treatment increased from 3% in 1999 to 13% in 2006, but the percentage of patients treated with postmastectomy radiotherapy dropped from 69% in 1999 to 66% in 2006 (P < 0.05). As regards the changes in techniques from 1999 to 2006, the use of special immobilization devices, treatment planning systems, and CT simulations increased from 46% to 80%, 23% to 70%, and 0% to 14%, respectively (P <0.01). From 1999 to 2006, irradiation of the chest wall following mastectomy increased from 67% to 90%, but for internal mammary irradiation it decreased from 76% to 30% and for the axilla, from 69% to 37% (P < 0.01). There were no obvious differences between 1999 and 2006 on the field design, boost treatment on the tumor bed, or dose prescription. CONCLUSIONS: Breast-conserving treatment was performed more frequently in China in 2006 than in 1999, but postmastectomy radiotherapy did not change a great deal and it was still an essential option. Although the international treatment guidelines have been accepted and implemented by physicians in recent years, prompt improvement in the quality of breast cancer radiotherapy is needed.

Video-Assisted Thoracoscopic Lobectomy Versus Stereotactic Body Radiotherapy Treatment for Early-Stage Non-Small Cell Lung Cancer: A Propensity Score-Matching Analysis.

BACKGROUND: Compared the overall outcomes of video-assisted thoracoscopic surgery (VATS) versus stereotactic body radiotherapy (SBRT) for stage I-II non-small cell lung cancer (NSCLC). METHODS: We retrospectively compared overall survival (OS), cancer-specific survival (CSS), locoregional control (LRC), and disease-free survival (DFS) at our institution between January 2012 and December 2016. Propensity score-matching was performed to reduce patient selection bias based on age, gender, Karnofsky performance score, Charlson comorbidity index, pulmonary function, and tumor diameter. RESULTS: A total of 567 patients treated with SBRT (n = 109) or surgery (n = 458) were included. Of those, 104 patients were matched for further analyses. Median follow-up was 44 months. At 3 and 5 years, OS was 88.6 and 79.9% for SBRT, and 94.2 and 91.6% for surgery (p = 0.097). There were no differences noted in 5-year CSS (83.7 vs. 91.6%, respectively; p = 0.270). The cumulative incidence of LRC at 3 and 5 years was comparable (93.5 and 93.5% vs. 94.0 and 85.9%, respectively; p = 0.621). Differences in the rates of disease-free survival at 5 years were not statistically significant (79.0 and 80.5%, respectively; p = 0.624). CONCLUSIONS: This propensity score-matching analysis suggests that SBRT can be an alternative option to VATS lobectomy for stage I-II NSCLC.

Network analysis of differentially expressed smoking-associated mRNAs, lncRNAs and miRNAs reveals key regulators in smoking-associated lung cancer.

Lung cancer is the leading cause of cancer-associated mortality worldwide. Smoking is one of the most significant etiological contributors to lung cancer development. However, the molecular mechanisms underlying smoking-induced induction and progression of lung cancer have remained to be fully elucidated. Furthermore, long non-coding RNAs (lncRNAs) are increasingly recognized to have important roles in diverse biological processes. The present study focused on identifying differentially expressed mRNAs, lncRNAs and micro (mi)RNAs in smoking-associated lung cancer. Smoking-associated co-expression networks and protein-protein interaction (PPI) networks were constructed to identify hub lncRNAs and genes in smoking-associated lung cancer. Furthermore, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses of differentially expressed lncRNAs were performed. A total of 314 mRNAs, 24 lncRNAs and 4 miRNAs were identified to be deregulated in smoking-associated lung cancer. PPI network analysis identified 20 hub genes in smoking-associated lung cancer, including dynein axonemal heavy chain 7, dynein cytoplasmic 2 heavy chain 1, WD repeat domain 78, collagen type III α 1 chain (COL3A1), COL1A1 and COL1A2. Furthermore, co-expression network analysis indicated that relaxin family peptide receptor 1, receptor activity modifying protein 2-antisense RNA 1, long intergenic non-protein coding RNA 312 (LINC00312) and LINC00472 were key lncRNAs in smoking-associated lung cancer. A bioinformatics analysis indicated these smoking-associated lncRNAs have a role in various processes and pathways, including cell proliferation and the cyclic guanosine monophosphate cGMP)/protein kinase cGMP-dependent 1 signaling pathway. Of note, these hub genes and lncRNAs were identified to be associated with the prognosis of lung cancer patients. In conclusion, the present study provides useful information for further exploring the diagnostic and prognostic value of the potential candidate biomarkers, as well as their utility as drug targets for smoking-associated lung cancer.