A Re-Examination of Neoadjuvant Therapy for Thymic Tumors: A Long and Winding Road.

For most patients with advanced thymic epithelial tumors (TETs), a complete resection is a strong indicator of a better prognosis. But sometimes, primary surgery is unsatisfactory, and preoperative therapy is needed to facilitate complete resection. Neoadjuvant chemotherapy is the most used form of preoperative therapy. But studies on neoadjuvant chemotherapy have included mainly patients with thymoma; its efficacy in patients with thymic carcinoma is less known. Neoadjuvant chemoradiation has also been explored in a few studies. Novel therapies such as immunotherapy and targeted therapy have shown efficacy in patients with recurrent/metastatic TETs as a second-line option; their role as preoperative therapy is still under investigation. In this review, we discuss the existing evidence on preoperative therapy and the insight it provides for current clinical practice and future studies.

Internal jugular vein pressure monitoring guided venous reconstruction could improve perioperative safety after superior vena cava resection for mediastinal tumors: a cohort study.

INTRODUCTION: After superior vena cava (SVC) resection, the decision on unilateral or bilateral reconstruction was mostly based on the expertise of surgeons without objective measurements. This study explored the use of internal jugular vein pressure (IJVP) monitoring to guide the SVC reconstruction strategy. METHODS: In a retrospective cohort, perioperative outcomes of unilateral and bilateral reconstruction based on surgeons' experience were compared. Then, IJVP threshold was measured when temporarily clamping the left innominate vein in a testing cohort. Venous reconstruction according to IJVP monitoring was performed in a prospective validation cohort afterward. Perioperative outcomes were compared between the prospective and the retrospective cohorts. For some interested variables, intuitive explanations would be given using Bayesian methods. Potential risk factors for postoperative complications were investigated by multivariable analysis. RESULTS: From March 2009 to September 2022, 57 patients underwent SVC reconstruction based on surgeons' experience. Bayesian analysis indicated a posterior probability of 80.49% that unilateral reconstruction had less blood loss than bilateral reconstruction (median 550 ml vs. 1200 ml). Cerebral edema occurred in two patients after unilateral reconstruction. In the testing cohort, median IJVP was 22.7 (18-27) cmH 2 O after temporary left innominate vein clamping in 10 patients. In the prospective cohort, unilateral reconstruction only was performed if the contralateral IJVP was <30 cmH 2 O in 16 patients. Bilateral reconstruction was performed if IJVP was ≥30 cmH 2 O after unilateral bypass in nine patients. No cerebral edema occurred in the prospective cohort. Less postoperative complications occurred in the prospective cohort than the retrospective cohort (12.0 vs. 38.6%, P =0.016). Upon multivariable analysis, IJVP-monitoring guided SVC reconstruction was associated with significantly less postoperative complications ( P =0.033). CONCLUSIONS: Intraoperative IJVP-monitoring is a useful strategy for selection of unilateral or bilateral SVC reconstruction and improving perioperative safety in patients with mediastinal tumors.

[Microbial remediation of cadmium-contaminated soils and its mechanisms: a review].

Excessive levels of cadmium (Cd) in soil exert serious negative impacts on soil ecosystems. Microorganisms are a common component of soil and show great potential for mitigating soil Cd. This review summarizes the application and remediation mechanisms of microorganisms, microbial-plants, and microbial-biochar in Cd-contaminated soil. Microorganisms such as Bacillus, Acinetobacter, Pseudomonas, and arbuscular mycorrhizal fungi (AMF) can change the biological validity of Cd through adsorption, mineralization, precipitation and dissolution. Different factors such as pH, temperature, biomass, concentration, and duration have significant effects on Cd bioavailability by microorganisms. Pseudomonas, Burkholderia, and Flavobacterium can promote the uptake of Cd2+ by hyperaccumulator through promotion and activation. Biochar, a soil amendment, possesses unique physicochemical properties and could act as a shelter for microorganisms in agriculture. The use of combined microbial-biochar can further stabilize Cd compared to using biochar alone.

A uniport subxiphoid approach with a modified sternum retractor is safe and feasible for anterior mediastinal tumors.

Background: Minimally invasive surgery has been used to treat anterior mediastinal tumors. This study sought to describe a single team's experience of uniport subxiphoid mediastinal surgery using a modified sternum retractor. Methods: Patients who underwent uniport subxiphoid video-assisted thoracoscopic surgery (USVATS) or unilateral video-assisted thoracoscopic surgery (LVATS) from September 2018 to December 2021 were retrospectively enrolled in this study. A 5-cm vertical incision approximately 1-cm caudal to the xiphoid process was usually made followed by the installment of a modified retractor, which was able to raise the sternum by 6-8 cm. Next, the USVATS was performed. In the unilateral group, 3 1-cm incisions were usually made, among which, 2 are made in the 2nd or 3rd and 5th intercostal anterior axillary line, and the 3rd was made in the 5th intercostal midclavicular line. In some instances, an additional subxiphoid incision was made to remove the large tumors. All the clinical and perioperative data, including the prospectively recorded visual analogue scale (VAS) score, were analyzed. Results: In total, 16 patients who underwent USVATS and 28 patients who underwent LVATS were enrolled in this study. With the exception of tumor size (USVATS 7.9±1.6 cm vs. LVATS 5.1±2.4 cm, P<0.001), the baseline data of the patients in the 2 groups were comparative. Blood loss in surgery, conversion, draining duration, postoperative stay, postoperative complications, pathology and tumor invasion were similar between the 2 groups. Although the operation time was significantly longer in the USVATS group than the LVATS group (115±19 vs. 83±30 min, P<0.001), the VAS score at 1st postoperative day (1.9±1.1 vs. 3.1±1.1, P<0.001) and moderate pain level (a VAS score >3) (6.3% vs. 32.1%, P=0.049) were better in the USVATS group than the LVATS group. Conclusions: Uniport subxiphoid mediastinal surgery is a feasible and safe procedure, especially for large tumors. Our modified sternum retractor is especially helpful during uniport subxiphoid surgery. Compared to lateral thoracic surgery, this approach has the advantages of less injury and lower postoperative pain, which may lead to a faster recovery. However, its long-term follow-up outcomes need to be observed.

Minimally Invasive Thymectomy Could Be Attempted for Locally Advanced Thymic Malignancies: A Real-World Study With Propensity Score-Matched Analysis.

INTRODUCTION: Increasing evidence supports minimally invasive thymectomy (MIT) for early stage thymic malignancies than open median sternotomy thymectomy (MST). Nevertheless, whether MIT could be attempted for locally advanced disease remains unclear. METHODS: The clinical data of consecutive patients with stage T2-3NxM0 (eighth edition TNM staging) thymic malignancies who underwent MIT or MST were identified from a prospectively maintained database. The co-resected structures were rated with a resection index to evaluate surgical difficulty. The impact of surgical approach on treatment outcomes was investigated through propensity score-matched analysis and multivariable analysis. RESULTS: From January 2008 to December 2019, a total of 128 patients were included; MIT was initially attempted in 58 (45.3%) cases, and eight (13.8%) were converted to MST during surgery. The conversion group had similar perioperative outcomes to the MST group, except for a longer operation time. After propensity score matching, the resection index scores were similar between the MIT and MST groups (3.5 versus 3.7, p = 0.773). The MIT group had considerably less blood loss (p < 0.001), fewer postoperative complications (p = 0.048), a shorter duration of chest drainage (p < 0.001), and a shorter hospitalization duration (p < 0.001) than the MST group. The 5-year freedom from recurrence rate was not different between the two groups (78.2% versus 78.5%, p = 0.942). In multivariable analysis, surgical approach was not associated with freedom from recurrence (p = 0.727). CONCLUSIONS: MIT could be safely attempted in carefully selected patients with locally advanced thymic tumors. Conversion did not compromise the surgical outcomes. Patients may benefit from the less traumatic procedure and thus better recovery, with comparable long-term oncologic outcomes.

Impact of Lymph Node Dissection on Survival After Neoadjuvant Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

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.

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010.

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 surgery 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: recurrence 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 locoregional 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 interval, 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 suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence. CONCLUSIONS: Prerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.

Discovery of Quinacrine as a Potent Topo II and Hsp90 Dual-Target Inhibitor, Repurposing for Cancer Therapy.

Topo II and Hsp90 are promising targets. In this study, we first verified the structural similarities between Topo IIα ATPase and Hsp90α N-ATPase. Subsequently, 720 compounds from the Food and Drug Administration (FDA) drug library and kinase library were screened using the malachite green phosphate combination with the Topo II-mediated DNA relaxation and MTT assays. Subsequently, the antimalarial drug quinacrine was found to be a potential dual-target inhibitor of Topo II and Hsp90. Mechanistic studies showed that quinacrine could specifically bind to the Topo IIα ATPase domain and inhibit the activity of Topo IIα ATPase without impacting DNA cleavage. Furthermore, our study revealed that quinacrine could bind Hsp90 N-ATPase and inhibit Hsp90 activity. Significantly, quinacrine has broad antiproliferation activity and remains sensitive to the multidrug-resistant cell line MCF-7/ADR and the atypical drug-resistant tumor cell line HL-60/MX2. Our study identified quinacrine as a potential dual-target inhibitor of Topo II and Hsp90, depending on the ATP-binding domain, positioning it as a hit compound for further structural modification.

Management of incidentally detected small anterior mediastinal nodules: Which way to go?

OBJECTIVES: With increasing use of CT screening for lung cancers, there is a tendency toward increased detection of asymptomatic small anterior mediastinal nodules (SAMNs). In face of high rate of non-therapeutic surgery in these patients, workup and follow-up strategy for such lesions remains to be established. MATERIALS AND METHODS: This is a real-world study in patients with SAMNs (baseline diameter ≤ 3 cm) during 2013-2018. Interval growth of the nodules was reviewed. Accuracy of preoperative diagnosis was evaluated, and tumor doubling time (TDT) was calculated in resected tumors. RESULTS: A total of 419 patients were entered into the study, among them 91 received surgery. Eighty-four patients (92.3%) turned out to have thymic tumors, with a non-therapeutic surgery rate of only 6.6%. For 73 patients receiving both CT and MRI examinations, the sensitivity for diagnosing thymic tumors by CT alone was merely 72.1%, which was significantly improved to 97.1% (p < 0.001) when MRI was incorporated. Among 38 thymic tumor patients who had previous CT scan before surgery, significant difference in median TDT was seen between low-grade tumors and intermediate-/high-grade tumors (23.8 vs. 10.1 months, p = 0.021). Of the 328 patients not receiving surgery, 269 (82.0%) were diagnosed of having benign cysts by CT + MRI, followed by 24 (7.3%) lymph nodes, 22 (6.7%) thymic hyperplasia, and 13 (4%) thymic tumors. During follow-up (median 33 months), 319 (97.3%) lesions remained unchanged. CONCLUSION: The majority of incidentally detected SAMNs remain stable during long-term follow-up. Incorporating MRI with CT scan is helpful in differentiating benign cysts from small thymic tumors, thus avoiding non-therapeutic intervention. Follow-up is safe and warranted upon first detection when high-grade malignancies could be ruled out by careful imaging studies.

Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial.

Platinum-based chemotherapy is the standard first-line treatment for advanced esophageal squamous cell carcinoma (ESCC). In this phase 3 study (ClinicalTrial.gov: NCT03829969), 514 patients with treatment-naïve advanced ESCC were randomized (1:1) to receive toripalimab or placebo in combination with paclitaxel plus cisplatin (TP) every 3 weeks for up to 6 cycles, followed by toripalimab or placebo maintenance. At the prespecified final analysis of progression-free survival (PFS), a significant improvement in PFS is observed for the toripalimab arm over the placebo arm (hazard ratio [HR] = 0.58; 95% CI, 0.46-0.74; p < 0.0001). The prespecified interim analysis of overall survival (OS) also reveals a significant OS improvement for patients treated with toripalimab plus TP over placebo plus TP (HR = 0.58; 95% CI, 0.43-0.78; p = 0.0004). The incidences of grade ≥3 treatment-emergent adverse events are similar between the two arms. Toripalimab plus TP significantly improves PFS and OS in patients with treatment-naïve, advanced ESCC, with a manageable safety profile.

Study protocol of an open-label prospective phase II umbrella study of precise neoadjuvant therapy for patients with stage II-IIIB resectable non-small cell lung cancer (PURPOSE).

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.

Clinical characteristics and survival of esophageal cancer patients: annual report of the surgical treatment in Shanghai Chest Hospital, 2016.

Background: Esophageal cancers present a significant burden of disease and remain one of the most lethal of cancers worldwide, particular in China. Surgical treatment remains the cornerstone of esophageal cancers, and a real-world data from a high-volume esophageal cancer center have guiding significance in evaluation of the current clinical practice. This report describes the clinical characteristics, treatment outcomes, and survival of surgical treatment in patients with esophageal cancer in Shanghai Chest Hospital (SCH). Methods: All patients diagnosed with esophageal cancer who received esophagectomy or endoscopic resection at SCH in 2016 were included in this study. The baseline characteristics, treatment-related outcomes, and follow-up data were collated from the medical records and a prospectively maintained database. The clinicopathological characteristics, surgical complications, and oncologic outcomes were summarized. Kaplan-Meier method was used to estimate their survival and Cox regression model was used to estimate the associated risk factors. Results: In 2016, a total of 546 patients with esophageal cancer received surgical or endoscopic resection at SCH (including 517 esophagectomies and 29 endoscopic resections). Most patients (52.4%) were between 60-69 years old, 79.5% were male, and for more than half of all patients (51.3%), the tumor was located at the middle thoracic esophagus. Overall, 11.0% (60/546) of patients received neoadjuvant therapy and 45.8% (250/546) of patients were treated with adjuvant therapy. Minimally invasive esophagectomy (including thoracoscopy and robot-assisted) was performed in 58.0% of patients and the R0 resection rate was 90.3%. The postoperative 30- and 90-day mortality was 0.73% and 1.1%, respectively. For the esophagectomy cohort, the 1-, 2-, 3-, 4-, and 5-year overall survival (OS) rates were 86.5%, 67.8%, 59.9%, 54.5%, 51.8%, and for cancer specific survival (CSS), the rates were 91.8%, 74.2%, 66.6%, 61.2%, and 59.1%, respectively. Conclusions: Through a standardized surgical procedure, the short- and long-term outcomes of patients with esophageal cancer were acceptable with good safety and oncological control in a high-volume center in China. This study reveals important surgical treatment effects of esophageal cancer patients and contributes to improvement of clinical management and future treatment development.

Novel Tumor-Specific Antigens for Immunotherapy Identified From Multi-omics Profiling in Thymic Carcinomas.

Thymic carcinoma (TC) is the most aggressive thymic epithelial neoplasm. TC patients with microsatellite instability, whole-genome doubling, or alternative tumor-specific antigens from gene fusion are most likely to benefit from immunotherapies. However, due to the rarity of this disease, how to prioritize the putative biomarkers and what constitutes an optimal treatment regimen remains largely unknown. Therefore, we integrated genomic and transcriptomic analyses from TC patients and revealed that frameshift indels in KMT2C and CYLD frequently produce neoantigens. Moreover, a median of 3 fusion-derived neoantigens was predicted across affected patients, especially the CATSPERB-TC2N neoantigens that were recurrently predicted in TC patients. Lastly, potentially actionable alterations with early levels of evidence were uncovered and could be used for designing clinical trials. In summary, this study shed light on our understanding of tumorigenesis and presented new avenues for molecular characterization and immunotherapy in TC.

Pathological complete response after neoadjuvant treatment determines survival in esophageal squamous cell carcinoma patients (NEOCRTEC5010).

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.

Effect of Camrelizumab vs Placebo Added to Chemotherapy on Survival and Progression-Free Survival in Patients With Advanced or Metastatic Esophageal Squamous Cell Carcinoma: The ESCORT-1st Randomized Clinical Trial.

Importance: Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma. Objective: To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. Design, Setting, and Participants: This randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020). A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized. Interventions: Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All treatments were given intravenously every 3 weeks. Main Outcomes and Measures: Coprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). Results: Of the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumab-chemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively. Conclusions and Relevance: Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03691090.

Long-term Efficacy of Neoadjuvant Chemoradiotherapy Plus Surgery for the Treatment of Locally Advanced Esophageal Squamous Cell Carcinoma: The NEOCRTEC5010 Randomized Clinical Trial.

Importance: The prognosis of patients with locally advanced esophageal squamous cell carcinoma (ESCC) remains poor after surgery. Neoadjuvant chemoradiotherapy (NCRT) has been shown to potentially improve survival. Objective: To compare the treatment efficacy of NCRT plus surgery with surgery alone for long-term survival among patients with locally advanced ESCC. Design, Setting, and Participants: The Neoadjuvant Chemoradiotherapy for Esophageal Cancer 5010 study was a multicenter open-label randomized phase 3 clinical trial that enrolled patients between June 1, 2007, and December 31, 2014. Follow-up ended on December 31, 2019. The study was conducted at 8 centers in China. A total of 451 patients aged 18 to 70 years with thoracic ESCC stage T1-4N1M0/T4N0M0 were enrolled and randomized. Data were analyzed from December 1, 2019, to June 30, 2020. Interventions: Patients randomized to receive NCRT plus surgery (NCRT group) received preoperative chemotherapy (25 mg/m2 of vinorelbine on days 1 and 8 and 75 mg/m2 of cisplatin on day 1 or 25 mg/m2 of cisplatin on days 1 to 4) every 3 weeks for 2 cycles and concurrent radiotherapy (40.0 Gy, administered in 20 fractions of 2.0 Gy for 5 days per week) followed by surgery. Patients randomized to receive surgery alone (surgery group) underwent surgery after randomization. Main Outcomes and Measures: The primary end point was overall survival in the intention-to-treat population. The secondary end point was disease-free survival. Results: A total of 451 patients (mean [SD] age, 56.5 [7.0] years; 367 men [81.4%]) were randomized to the NCRT (n = 224) and surgery (n = 227) groups and were eligible for the intention-to-treat analysis. By December 31, 2019, 224 deaths had occurred. The median follow-up was 53.5 months (interquartile range, 18.2-87.4 months). Patients receiving NCRT plus surgery had prolonged overall survival compared with those receiving surgery alone (hazard ratio, 0.74; 95% CI, 0.57-0.97; P = .03), with a 5-year survival rate of 59.9% (95% CI, 52.9%-66.1%) vs 49.1% (95% CI, 42.3%-55.6%), respectively. Patients in the NCRT group compared with the surgery group also had prolonged disease-free survival (hazard ratio, 0.60; 95% CI, 0.45-0.80; P < .001), with a 5-year survival rate of 63.6% (95% CI, 56.0%-70.2%) vs 43.0% (95% CI, 36.0%-49.7%), respectively. Conclusions and Relevance: In this randomized clinical trial, treatment with NCRT plus surgery significantly improved long-term overall survival and disease-free survival and therefore may be considered a standard of care for patients with locally advanced ESCC. Trial Registration: ClinicalTrials.gov Identifier: NCT01216527.

The possibility of endoscopic treatment of cN0 submucosal esophageal cancer: results from a surgical cohort.

BACKGROUND: We analyzed the pathological characteristics and recurrence pattern of cN0 submucosal esophageal cancer after esophagectomy and conducted risk stratification to determine the feasibility of performing endoscopic resection for cN0pT1b esophageal squamous cell malignancies. METHODS: We retrospectively enrolled 167 patients who underwent right-sided transthoracic esophagectomy and extended thoracic/abdominal two-field lymphadenectomy. Patients with pathologically confirmed lymph node metastasis or tumor recurrence constituted the high-risk group for endoscopic submucosal resection, and the remainder were defined as low risk. Factors affecting lymphatic metastasis and long-term recurrence were identified by univariate and multivariate analyses. RESULTS: Postoperative pathology showed that five patients (5/167; 3%) had lymph node metastases. Follow-up ranged from 12-60 months, with a median of 29 months. A total of 17 patients (10.2%) had recurrences during follow-up, including three patients with pathologic nodal metastasis (pN +) found at surgery. Invasion depth, differentiation, and tumor size differed significantly in high-risk patients. Overall 3-year survival rates were 94.2% (low-risk) and 40.9% (high-risk) (p < 0.01). Twenty-one patients with sm1 cancer, high tumor differentiation, and tumor length < 2 cm had no lymph node metastasis or lymphovascular invasion, and none of these patients experienced recurrence. CONCLUSIONS: Endoscopic submucosal resection alone may be feasible for patients with small (≤ 2 cm) clinically N0 submucosal esophageal squamous cell carcinoma with low invasion depth (sm1) and higher differentiation, but prospective studies are required for confirmation. Other patients require surgical resection with extended two-field thoracic/abdominal lymphadenectomy.

Prognostic Impact of Postoperative Lymph Node Metastases After Neoadjuvant Chemoradiotherapy for Locally Advanced Squamous Cell Carcinoma of Esophagus: From the Results of NEOCRTEC5010, a Randomized Multicenter Study.

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.

A Recurrence Predictive Model for Thymic Tumors and Its Implication for Postoperative Management: a Chinese Alliance for Research in Thymomas Database Study.

OBJECTIVE: Our aim was to investigate appropriate postoperative management based on the risk of disease recurrence in thymic epithelial tumors after complete resection. METHODS: The Chinese Alliance for Research in Thymomas retrospective database was reviewed. Patients having stage I to IIIa tumors without pretreatment and with complete resection were included. Clinicopathologic variables with statistical significance in the multivariate Cox regression were incorporated into a nomogram for building a recurrence predictive model. RESULTS: A total of 907 cases, including 802 thymomas, 88 thymic carcinomas, and 17 neuroendocrine tumors, were retrieved between 1994 and 2012. With a median follow-up of 52 months, the 10-year overall survival rate was 89.5%. Distant and/or locoregional recurrences were noted in 53 patients (5.8%). The nomogram model revealed histologic type and T stage as independent predictive factors for recurrence, with a bootstrap-corrected C-index of 0.86. On the basis of this model, patients with T1 thymomas or T2 or T3 type A, AB, or B1 thymomas had a significantly lower incidence of recurrence (low-risk group) than those with T2 or T3 type B2 or B3 thymomas and all thymic carcinomas and neuroendocrine tumors (high-risk group) (2.7% versus 20.1% [p < 0.001]). In the high-risk group, more than half of the recurrences (55.2% [16 of 29]) were seen within the first 3 postoperative years, whereas all recurrences but one were recorded within 6 years after surgery. Recurrence occurred quite evenly over 10 postoperative years in the low-risk group. CONCLUSIONS: A 6-year active surveillance should be considered in high-risk patients regardless of adjuvant therapy. For low-risk patients, annual follow-up may be sufficient. Studies examining postoperative adjuvant therapies would be plausible in high-risk patients.

Pulmonary echinococcosis in China.

Pulmonary echinococcosis is a zoonotic parasitic disease caused by the larval stage of cestodes belonging to the genus echinococcus, which is the top killer of residents in pastoral areas and requires more attention. Prevention is the top priority; screening is another important strategy. Surgery is still the preferred treatment for pulmonary echinococcosis. Fortunately, the Chinese government has equipped each county hospital with CT machines. In the foreseeable future, the screening for pulmonary echinococcosis will begin in many areas including Tibet, which will allow us to cure early pulmonary echinococcosis in a more minimally-invasive way.