Considerations for multidisciplinary management of synchronous primary breast cancer and primary lung cancer - Analysis of thirty-one patients.

BACKGROUND: The simultaneous (synchronous) presence of primary breast cancer and primary lung cancer diagnosed in a single individual is not an uncommon phenomenon. However, reference data for treatment strategy is scarce and "chaotic". In the present study we discuss the management strategy for this group of patients. METHODS: We retrospectively reviewed patients in the primary breast cancer database of the Breast Center and the primary lung cancer database of the Thoracic Surgery Department I of Peking University Cancer Hospital. Patients with synchronous primary breast cancer and primary lung cancer who underwent surgery between December 2010 and December 2023 were included in the study. The sequence of outpatient visits, recommendations of multidisciplinary teams, perioperative treatment, and surgical procedures were reviewed. Meanwhile, survival analysis based on propensity score matching with 1:1 ratio was performed between the 31 patients and those with lung cancer only during the same period. RESULTS: A total of 31 patients with synchronous primary breast cancer and primary lung cancer were identified; all of the patients were women. The average age was 61 years. A total of 24 of the patients had visited the breast center first, and routine chest computed tomography (CT) showed evidence of primary lung cancer. The other seven patients had visited the thoracic surgery clinic first, and routine positron emission tomography (PET)-CT revealed the coexistence of primary breast cancer. All the patients had multidisciplinary team consultations, after which 20 patients were recommended to have preoperative treatment for breast cancer, two patients were recommended to have preoperative treatment for lung cancer, and nine patients were recommended to undergo surgery directly. After surgery, 23 patients received postoperative adjuvant treatment for breast cancer, and no patients needed postoperative adjuvant treatment for lung cancer. Survival analysis showed that there was no significant difference between the 31 patients and those with lung cancer only. CONCLUSION: Routine chest CT is needed for breast cancer patients before surgery, and PET-CT is required for the accurate staging of lung cancer patients. A multidisciplinary expert team should manage synchronous primary breast cancer and primary lung cancer. Emphasis should be placed on patients who need preoperative treatment before surgery. Particularly, for patients who need preoperative chemotherapy, a regimen should be chosen that balances the treatment of lung cancer and breast cancer.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

Erlotinib versus gemcitabine plus cisplatin as neoadjuvant treatment of stage IIIA-N2 EGFR-mutant non-small-cell lung cancer: final overall survival analysis of the EMERGING-CTONG 1103 randomised phase II trial.

EMERGING-CTONG 1103 showed improved progression-free survival (PFS) with neoadjuvant erlotinib vs. chemotherapy for patients harbouring EGFR sensibility mutations and R0 resected stage IIIA-N2 non-small cell lung cancer (NSCLC) (NCT01407822). Herein, we report the final results. Recruited patients were randomly allocated 1:1 to the erlotinib group (150 mg/day orally; neoadjuvant phase for 42 days and adjuvant phase to 12 months) or to the GC group (gemcitabine 1250 mg/m2 plus cisplatin 75 mg/m2 intravenously; 2 cycles in neoadjuvant phase and 2 cycles in adjuvant phase). Objective response rate (ORR), complete pathologic response (pCR), PFS, and overall survival (OS) were assessed along with safety. Post hoc analysis was performed for subsequent treatments after disease recurrence. Among investigated 72 patients (erlotinib, n = 37; GC, n = 35), the median follow-up was 62.5 months. The median OS was 42.2 months (erlotinib) and 36.9 months (GC) (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.47-1.47; p = 0.513). The 3- and 5-year OS rates were 58.6% and 40.8% with erlotinib and 55.9% and 27.6% with GC (p3-y = 0.819, p5-y = 0.252). Subsequent treatment was administered in 71.9% and 81.8% of patients receiving erlotinib and GC, respectively; targeted therapy contributed mostly to OS (HR, 0.35; 95% CI, 0.18-0.70). After disease progression, the ORR was 53.3%, and the median PFS was 10.9 months during the EGFR-TKI rechallenge. During postoperative therapy, grade 3 or 4 adverse events (AEs) were 13.5% in the erlotinib group and 29.4% in the GC group. No serious adverse events were observed. Erlotinib exhibited clinical feasibility for resectable IIIA-N2 NSCLC over chemotherapy in the neoadjuvant setting.

Pre-operative oil ingestion reduces the probability of thoracic duct trunk ligation during esophagectomy.

Chylothorax is an important complication after esophagectomy. Ligation of the injured thoracic duct is the main method to prevent chylothorax after esophagectomy, but may be associated with adverse effects. Whether ligation of the injured tributary alone, keeping the main trunk intact, may suffice to prevent post-operative chylothorax is not well known. Since March 2017, 40 mL of olive oil was administered to patients posted for esophagectomy. We compared patients admitted between March 2017 and December 2019 with patients admitted between July 2014 and February 2017, who had not received pre-operative oil. The outcome measures were the need for thoracic duct main trunk or tributary ligation, development of chylothorax and missed ligation. There were 371 patients in the oil ingestion group and 308 patients in the standard control group. Chylothorax in the oil ingestion group was significantly lower than that in the standard control group (1.3% vs. 4.5%, P = 0.012). Chyle leak from thoracic duct tributaries was diagnosed in a significantly higher percentage (5.7% vs. 0.0%, P < 0.001) and missed ligation of the injured thoracic duct was significantly lower (0.3% vs. 3.9%, P = 0.002) in the oil ingestion group compared with the standard control group. The incidence of post-operative chylothorax was not statistically different (6.3% vs. 10.0%, P = 1.000) between the tributary and the trunk ligation group. Pre-operative oil ingestion can help visualize the thoracic duct trunk and its tributaries during esophagectomy. Thus, non-selected thoracic duct trunk ligation and missed ligation during esophagectomy can be reduced. Precise ligation of the injured tributary while the main trunk is intact can also prevent post-operative chylothorax.

Adebrelimab (SHR-1316) in Combination With Chemotherapy as Perioperative Treatment in Patients With Resectable Stage II to III NSCLCs: An Open-Label, Multicenter, Phase 1b Trial.

INTRODUCTION: This study evaluated adebrelimab (a programmed death-ligand 1 antibody) plus nab-paclitaxel and carboplatin as perioperative treatment for resectable NSCLC. METHODS: Eligible patients had resectable stage II to III NSCLCs without driver gene. Patients received neoadjuvant treatment with three cycles of intravenous adebrelimab (20 mg/kg on day 1), nab-paclitaxel (100 mg/m2 on days 1, 8, and 15), and carboplatin (area under the curve 5 mg/mL per min on day 1), of each 21-day cycle before surgical resection, and followed by 16 cycles of adebrelimab (20 mg/kg on day 1 in 3 wk) adjuvant treatment. The primary end point was major pathologic response (MPR) per blinded independent pathologic review. RESULTS: A total of 37 patients were enrolled and received planned neoadjuvant therapy. There were 34 patients (91.9%) who underwent surgery. As of data cutoff on January 25, 2022, 19 of the 37 patients (51.4%, 95% confidence interval [CI]: 35.9-66.6) achieved MPR per blinded independent pathologic review and 11 patients (29.7%, 95% CI: 17.5-45.8) achieved pathologic complete response. Furthermore, 26 patients (70.3%, 95% CI: 54.2-82.5) had an objective response per Response Evaluation Criteria in Solid Tumors version 1.1. The 12-month event-free survival rate was 77.8% (95% CI: 54.1-90.3). In addition, 29 patients (78.4%) had grade greater than or equal to three treatment-related adverse events (AEs) and nine (24.3%) had treatment-related serious AEs. No treatment-related deaths occurred. Grade greater than or equal to three surgery-related AEs within 30 or 90 days after surgery were both reported in five patients (14.7%). CONCLUSIONS: Adebrelimab plus nab-paclitaxel and carboplatin as perioperative therapy led to a substantial proportion of MPR and high resectability, with manageable toxicities. On the basis of the phase 1b results, phase 3 trial was initiated.

Endobronchial ultrasound-guided transbronchial needle aspiration in patients with previously treated malignancies: diagnostic performance and predictive value.

BACKGROUND: Endobronchial ultrasound-guided transbronchial needle aspiration is a minimally invasive and effective sampling approach for patients with mediastinal or hilar lymphadenopathy. Increased recognition of the ultrasonographic features revealed the value of its images in predicting mediastinal lymph node malignancy. However, its diagnostic validity and the predictive value of its ultrasonographic features have not been demonstrated well in patients after systemic anti-tumor therapy. This study aimed to evaluate the efficiency of endobronchial ultrasound-guided transbronchial needle aspiration in patients with suspicious lymph nodes after anti-tumor therapy. METHODS: We retrospectively reviewed cases of endobronchial ultrasound-guided transbronchial needle aspiration performed between January 2019 and August 2021 at a single tertiary hospital center. Patients with suspected mediastinal or hilar lymph nodes within 5 years of systemic anti-tumor therapy were enrolled. Final diagnoses were determined by pathologic diagnoses of samples from transbronchial needle aspiration, surgery, or follow-up for at least 6 months. Ultrasonographic features were analyzed to assess the predictive value of malignant lymph nodes after treatment. RESULTS: Overall, 168 lymph nodes of 138 patients were analyzed. Among 110 (65.5%) malignant lymph nodes, 75 originated from lung cancers; the other 35 were from other malignancies. No complications related to endobronchial ultrasound-guided transbronchial needle aspiration were observed. Of 58 negative results of transbronchial needle aspiration, 51 were proven to be true negatives; 7 were false. The overall sensitivity and the negative predictive value were 94.02% and 87.93%, respectively. Univariate and multivariate analysis revealed the absence of central hilar structure and short axis > 10 mm as independent predictive factors for malignancy. CONCLUSIONS: Endobronchial ultrasound-guided transbronchial needle aspiration performs satisfactorily in diagnosing mediastinal and hilar lymphadenopathy even after anti-tumor treatment.

IGFBP1hiWNT3Alo Subtype in Esophageal Cancer Predicts Response and Prolonged Survival with PD-(L)1 Inhibitor.

PD-(L)1 inhibitor could improve the survival of locally advanced esophageal cancer (ESCA) patients, but we cannot tailor the treatment to common biomarkers. WNT signaling activation was associated with primary resistance to immunotherapy. In this study, we used our two clinical cohorts (BJCH n = 95, BJIM n = 21) and three public cohorts to evaluate and verify a new immunotherapeutic biomarker based on WNT signaling in ESCA patients. Our findings showed that WNT signaling-related genes stratified TCGA patients into Cluster 1, 2, and 3, among which, Cluster 3 had the worst prognosis. The most up- and down-regulated genes in Cluster 3 were IGFBP1 and WNT3A. Further analysis validated that IGFBP1hiWNT3Alo ESCA patients had significantly poor RFS and OS in the TCGA and BJCH cohorts. Interestingly, IGFBP1hiWNT3Alo patients had a good response and prognosis with immunotherapy in three independent cohorts, exhibiting better predictive value than PD-L1 expression (signature AUC = 0.750; PD-L1 AUC = 0.571). Moreover, IGFBP1hiWNT3Alo patients may benefit more from immunotherapy than standard treatment (p = 0.026). Immune cell infiltration analysis revealed a significant increase in DC infiltration in IGFBP1hiWNT3Alo patients post-immunotherapy (p = 0.022), which may enhance immune response. The IGFBP1hiWNT3Alo signature could predict patients who benefited from PD-(L)1 inhibitor treatment and may serve as a biomarker in ESCA.

Malignant transformation of heterotopic pancreas as middle esophagus adenocarcinoma-A rare case report and comprehensive literature review.

Heterotopic pancreas is a rare congenital abnormality that occurs during the growth and development process. It can be found in any part of the digestive tract, but the most common sites are the stomach, duodenum, and jejunum. Malignant transformation especially in the esophagus is rare. Here, we aim to report an unusual case of mid-esophageal adenocarcinoma that originated from a heterotopic pancreas.

Risk factors for early local lymph node recurrence of thoracic ESCC after McKeown esophagectomy.

Objectives: Even underwent radical resection, some patients of thoracic esophageal squamous cell carcinoma (ESCC) are still exposed to local recurrence in a short time. To this end, the present study sought to differentiate patient subgroups by assessing risk factors for postoperative early (within one year) local lymph node recurrence (PELLNR). Methods: ESCC patients were selected from a prospective database, and divided into high- and low-risk groups according to the time of their local lymphatic recurrence (within one year or later). Survival analysis was conducted by the Cox regression model to evaluate the overall survival (OS) between the two groups. The hazard ratio (HR) and 95% confidence interval (CI) of different variables were also calculated. Logistic regression analysis was used to explore the high-risk factors for PELLNR with the odds ratio (OR) and 95% CI calculated. Results: A total of 432 cases were included. The survival of patients in the high-risk group (n = 47) was significantly inferior to the low-risk group (n = 385) (HR = 11.331, 95% CI: 6.870-16.688, P < 0.001). The 1-year, 3-year, and 5-year OS rate of the patients in high/low-risk groups were 74.5% vs. 100%, 17% vs. 88.8%, and 11.3% vs. 79.2%, respectively (P < 0.001). Risk factors for local lymph node recurrence within one year included upper thoracic location (OR = 4.071, 95% CI: 1.499-11.055, P = 0.006), advanced T staging (pT3-4, OR = 3.258, 95% CI: 1.547-6.861, P = 0.002), advanced N staging (pN2-3, OR = 5.195, 95% CI: 2.269-11.894, P < 0.001), and neoadjuvant treatment (OR = 3.609, 95% CI: 1.716-7.589, P = 0.001). In neoadjuvant therapy subgroup, high-risk group still had unfavorable survival (Log-rank P < 0.001). Multivariate analysis demonstrated that upper thoracic location (OR = 5.064, 95% CI: 1.485-17.261, P = 0.010) and advanced N staging (pN2-3) (OR = 5.999, 95% CI: 1.986-18.115, P = 0.001) were independent risk factors for early local lymphatic recurrence. However, the cT downstaging (OR = 0.862, 95% CI: 0.241-3.086, P = 0.819) and cN downstaging (OR = 0.937, 95% CI: 0.372-2.360, P = 0.890) for patients in the neoadjuvant subgroup failed to lower PELLNR. The predominant recurrence field type was single-field. Conclusions: Thoracic ESCC patients with lymph node recurrence within one year delivered poor outcomes, with advanced stages (pT3-4/pN2-3) and upper thoracic location considered risk factors for early recurrence.

Lower Background Infusion of Oxycodone for Patient-Controlled Intravenous Analgesia, Combined with Ropivacaine Intercostal Nerve Block, in Patients Undergoing Thoracoscopic Lobectomy for Lung Cancer: A Randomized, Double-Blind, Controlled Clinical Trial.

PURPOSE: To compare the efficacy of a lower dose background infusion of oxycodone for patient-controlled intravenous analgesia (PCIA) with the conventional dose, following intercostal nerve block, for the management of postoperative pain in patients undergoing thoracoscopic lobectomy for lung cancer. PATIENTS AND METHODS: This was a prospective, single-center, randomized, parallel-group, double-blind, controlled clinical trial. In total, 155 patients scheduled for elective radical lobectomy via video-assisted thoracoscopy were recruited from December 2018 to July 2019, of whom 140 were ultimately included in the study population. Patients were randomized to receive either oxycodone 0.25 mg/h (low-dose group, n=70) or oxycodone 0.5 mg/h (control group, n=70) as a background infusion for PCIA, following ropivacaine intercostal nerve block, for postoperative pain management. The primary endpoints were rest and dynamic visual analogue scale (VAS) scores within 72 h of the operation. The secondary endpoints were patient satisfaction scores, consumption of postoperative analgesics, times of patient-controlled analgesia (PCA), and adverse events. RESULTS: All 140 enrolled patients completed the study requirements and were included in the final analysis. The rest and dynamic VAS scores at 4 h, 24 h, 48 h, and 72 h postoperative were comparable between the low-dose group and the control group (P>0.05). However, the low-dose group had statistically significantly higher patient satisfaction scores (P<0.001) and lower postoperative analgesic consumption (P<0.001) as well as lower incidence of nausea and vomiting (P<0.05). The times of PCA was not statistically significantly different between the two groups, and no serious adverse events occurred in either group (P>0.05). CONCLUSION: A low-dose background infusion of oxycodone for postoperative PCIA can achieve a comparable analgesic effect to the conventional dose after thoracoscopic lobectomy for lung cancer. Furthermore, the low-dose regimen was associated with reduced consumption of oxycodone and increased patient satisfaction.

Efficacy of programmed cell death protein 1 inhibitor in resection transformation treatment of esophageal cancer.

BACKGROUND: Surgery is an important component in the treatment of esophageal cancer. For patients not eligible for R0 resection, defined as locally advanced unresectable esophageal cancer, a new approach is to transform the cancer into a resectable state by preoperative treatment. However, preoperative chemo/radiation is unsatisfactory. Therefore, the aim of this study was to assess the safety and efficacy of chemo/radiotherapy combined with a programmed cell death protein 1 (PD-1) inhibitor in the preoperative transformation of unresectable esophageal cancer. METHODS: Patients were evaluated as having unresectable, locally advanced esophageal cancer at baseline and were re-evaluated as possible R0 resection candidates after PD-1 inhibitor treatment. Patient data were derived from the prospective database of Peking University Cancer Hospital Thoracic Surgery I. Preoperative chemotherapy plus PD-1 inhibitor treatment was defined as "transformation treatment." The objective response rate, operation rate (proportion of patients who underwent surgery), R0 rate, and treatment safety were analyzed retrospectively. RESULTS: A total of 36 patients were enrolled into the study, and 94.4% (34/36) completed the planned transformation treatment. The objective response rate was 71.4% (25/35), and 75% (27/36) of the patients who completed transformation treatment underwent surgery. For these surgical patients, 81.5% (22/27) obtained R0 resection, and 22.2% (6/22) had pathological complete response (pCR). During transformation treatment, 22.2% (8/36) patients had ≥ grade 3 complications. There were no reoperations or perioperative deaths. After surgery, 29.6% (8/27) had ≥ grade 3 complications. CONCLUSIONS: Esophagectomy after immunotherapy is safe with acceptable complications. Compared with chemotherapy alone, chemotherapy combined with immunotherapy had a more favorable transformation effect for patients with unresectable esophageal cancer.

Virtual bronchoscopic navigation without fluoroscopy guidance for peripheral pulmonary lesions in inexperienced pulmonologist.

OBJECTIVE: Fluoroscopy guidance is generally required for endobronchial ultrasonography with guide sheath (EBUS-GS) in peripheral pulmonary lesions (PPLs). Virtual bronchoscopic navigation (VBN) can guide the bronchoscope by creating virtual images of the bronchial route to the lesion. The diagnostic yield and safety profiles of VBN without fluoroscopy for PPLs have not been evaluated in inexperienced pulmonologist performing EBUS-GS. METHODS: Between January 2016 and June 2017, consecutive patients with PPLs referred for EBUS-GS at a single cancer center were enrolled. The diagnostic yield as well as safety profiles was retrospectively analyzed, and our preliminary experience was shared. RESULTS: A total of 109 patients with 109 lesions were included, 99 (90.8%) lesions were visible on EBUS imaging. According to the procedure time needed to locate the lesion on EBUS, 24.8% (27/109) were deemed technically difficult procedures; however, no significant relationships were identified between candidate parameters and technically difficult procedures. The overall diagnosis yield was 74.3% (81/109), and the diagnostic yield of malignancy was 83.7% (77/92). Lesions larger than 20 mm [odds ratio (OR), 2.758; 95% confidence interval (95% CI), 1.077-7.062; P=0.034] and probe of within type (OR, 3.174; 95% CI, 1.151-8.757, P=0.026) were independent factors leading to a better diagnostic yield in multivariate analysis. About 30 practice procedures were needed to achieve a stable diagnostic yield, and the proportion of technically difficult procedures decreased and stabilized after 70 practice procedures. Regarding complications, one patient (0.9%) had intraoperative hemorrhage (100 mL) which was managed under endoscopy. CONCLUSIONS: VBN without fluoroscopy guidance is still useful and safe for PPLs diagnosis, especially for malignant diseases when performed by pulmonologist without previous experience of EBUS-GS. VBN may simplify the process of lesion positioning and further multi-center randomized studies are warranted.

Efficacy of transcutaneous electrical acupoint stimulation combined with general anesthesia for sedation and postoperative analgesia in minimally invasive lung cancer surgery: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Multimodal opioid-sparing analgesia is a key component of an enhanced recovery pathway after surgery that aims to improve postoperative recovery. Transcutaneous electrical acupoint stimulation (TEAS) is assumed to alleviate pain and anxiety and to modify the autonomic nervous system. This study aimed to determine the efficacy of TEAS for sedation and postoperative analgesia in lung cancer patients undergoing thoracoscopic pulmonary resection. METHODS: A total of 80 patients were randomized into two groups: the TEAS group and the sham TEAS combined with general anesthesia group. Postoperative pain levels at six, 24, 48 hours, and one month after surgery were measured using the visual analogue scale (VAS). Bispectral index (BIS) score during the TEAS prior to anesthetic induction, Observer's Assessment of Alertness/Sedation (OAAS) score, sufentanil consumption during postoperative patient-controlled intravenous analgesia (PCIA), number of total and effective attempts of PCIA pump use, and incidence of postoperative nausea and vomiting were recorded and analyzed statistically. RESULTS: Patients in the TEAS group had significantly lower VAS scores at six, 24, and 48 hours after surgery (P < 0.01); lower BIS scores at 10, 20, and 30 minutes before induction (P < 0.01); lower levels of postoperative sufentanil consumption; lower number of PCIA attempts and effective rates (P < 0.01); lower incidences of nausea at 0, six, 24, and 48 hours; and lower incidence of vomiting at 24 hours after surgery (P < 0.05). The postoperative OAAS scores were similar between the groups. CONCLUSIONS: TEAS could be a feasible approach for sedation and postoperative analgesia in thoracoscopic pulmonary resection.

HOXB7 mediates cisplatin resistance in esophageal squamous cell carcinoma through involvement of DNA damage repair.

BACKGROUND: DNA damage repair is an important mechanism of platinum resistance. HOXB7 is one member of HOX family genes, which are essential developmental regulators and frequently dysregulated in cancer. Recently, its relevance in chemotherapy resistance and DNA damage repair has also been addressed. However, little is known regarding the association between HOXB7 and chemotherapy resistance in esophageal squamous cell carcinoma (ESCC). METHODS: The association between HOXB7 expression detected by immunohistochemisty and tumor regression grade (TRG) and long-term survival was analyzed in 143 ESCC patients who underwent neoadjuvant chemotherapy. CCK8 assay was used to examine the effect of cisplatin in a panel of four ESCC cell lines. A stable cell strain with HOXB7 knockdown of KYSE150 and KYSE450 was established to explore the effect on cisplatin sensitivity. The interaction of HOXB7 with Ku70, Ku80 and DNA-PKcs was determined by GST-pull down, coimmunoprecipitation and immunofluorescent colocalization. Finally, we investigated whether disrupting HOXB7 function by a synthetic peptide HXR9 blocking the formation of HOXB7/PBX could enhance cisplatin sensitivity in vitro and in vivo. RESULTS: High expression of HOXB7 was associated with cisplatin resistance and worse chemotherapy efficacy. HOXB7 knockdown reinforced cisplatin sensitivity. It was identified that HOXB7 interacts with Ku70, Ku80 and DNA-PKcs. HOXB7 knockdown was related to the downregulation of Ku70, Ku80 and DNA-PKcs as well as arrested cell cycle in S phase. HOXB7 inhibition by HXR9 had a synergistic effect to improve cisplatin sensitivity. CONCLUSION: HOXB7 may be a biomarker for the prediction of chemoresistance of ESCC and serves as a promising therapeutic target.

Multiple Pulmonary Resections for Synchronous and Metachronous Lung Cancer at Two Chinese Centers.

BACKGROUND: To determine oncologic and surgical outcomes after multiple pulmonary resections (MPR) for synchronous or metachronous lung cancer with multiple pulmonary sites of involvement and to identify prognostic factors for these patients. METHODS: We retrospectively analyzed data from two Chinese high-volume institutions. Eligible patients underwent MPR for synchronous or metachronous lung cancer with multiple pulmonary sites of involvement. Overall survival and disease-free survival after MPR were analyzed, and prognostic factors were explored using multivariable Cox analysis. Postoperative mortality and major morbidities within 30 days were evaluated. RESULTS: In total, 142 patients were included: 36 (25%) underwent MPR for the metachronous disease, and 106 (75%) underwent MPR for the synchronous disease. Five-year disease-free survival was 85.4% for the metachronous group and 69.1% for the synchronous group; 5-year overall survival was 86.1% and 84.8%, respectively. Five-year accumulated local and distant recurrence rates were 11.9% and 3.0% for the metachronous group and 26.6% and 5.9% for the synchronous group, respectively. In the synchronous MPR group, a larger sum of tumor size (hazard ratio [HR] 1.04; 95% confidence interval [CI], 1.00 to 1.08) and regional nodal involvement (HR 6.17; 95% CI, 1.42 to 35.46) were both independently associated with worse overall survival. In the metachronous MPR group, the longer disease-free interval was independently associated with favorable overall survival (HR 0.94; 95% CI, 0.88 to 0.98) and disease-free survival (HR 0.96; 95% CI, 0.93 to 0.99). There was no 30-day mortality. The overall rate of major morbidities was 12%. CONCLUSIONS: Multiple pulmonary resection is valid for patients with synchronous and metachronous lung cancer with multiple pulmonary sites of involvement.

Genome-scale CRISPR activation screening identifies a role of ELAVL2-CDKN1A axis in paclitaxel resistance in esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) may provide survival benefits for patients with advanced esophageal squamous cell carcinoma. However, tumor cells can display primary or secondary resistance to paclitaxel (PTX), a primary component of induction chemotherapy regimen. To identify genes capable of conveying PTX resistance, we performed a genome-wide CRISPR transcriptional activation library in human KYSE-180 cells. High throughput next generation sequencing was further applied to establish the phenotype-to-genotype relationship. Our highest-ranking hits are CDKN1A, TSPAN4, ELAVL2, JUNB and PAAF1. We generated evidence that esophageal tumors with high CDKN1A, ELAVL2 and TSPAN4 levels, quantified using qRT-PCR and Western blot assays, showed poorer chemotherapy response. Higher expression levels of TSPAN4 and ELAVL2 protein are independent risk factors for poor chemotherapy response in ESCC patients. We then found that overexpression of CDKN1A, ELAVL2 or TSPAN4 in ESCC cell lines significantly promoted the resistance to PTX by inhibiting cell apoptosis. Interestingly, ESCC cells overexpressed CDKN1A, ELAVL2 or TSPAN4 also acquired resistance to cisplatin (DDP). This phenomenon may be explained by cross-resistance of chemotherapy. We additionally found an association between ELAVL2 and CDKN1A, which may be regarded as the upstream and downstream factors that synergistically involved in the regulation of chemo-resistance in ESCC. Therefore, our study demonstrated that the genome-wide CRISPR activation library is a powerful strategy for the discovery of chemo-resistant genes critical for ESCC and we reported the first evidence that the ELAVL2-CDKN1A axis may be an important mechanism involved in chemo-resistance in ESCC.

Erlotinib Versus Gemcitabine Plus Cisplatin as Neoadjuvant Treatment of Stage IIIA-N2 EGFR-Mutant Non-Small-Cell Lung Cancer (EMERGING-CTONG 1103): A Randomized Phase II Study.

PURPOSE: To assess the benefits of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors as neoadjuvant/adjuvant therapies in locally advanced EGFR mutation-positive non-small-cell lung cancer. PATIENTS AND METHODS: This was a multicenter (17 centers in China), open-label, phase II, randomized controlled trial of erlotinib versus gemcitabine plus cisplatin (GC chemotherapy) as neoadjuvant/adjuvant therapy in patients with stage IIIA-N2 non-small-cell lung cancer with EGFR mutations in exon 19 or 21 (EMERGING). Patients received erlotinib 150 mg/d (neoadjuvant therapy, 42 days; adjuvant therapy, up to 12 months) or gemcitabine 1,250 mg/m2 plus cisplatin 75 mg/m2 (neoadjuvant therapy, two cycles; adjuvant therapy, up to two cycles). Assessments were performed at 6 weeks and every 3 months postsurgery. The primary end point was objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; secondary end points were pathologic complete response, progression-free survival (PFS), overall survival, safety, and tolerability. RESULTS: Of 386 patients screened, 72 were randomly assigned to treatment (intention-to-treat population), and 71 were included in the safety analysis (one patient withdrew before treatment). The ORR for neoadjuvant erlotinib versus GC chemotherapy was 54.1% versus 34.3% (odds ratio, 2.26; 95% CI, 0.87 to 5.84; P = .092). No pathologic complete response was identified in either arm. Three (9.7%) of 31 patients and zero of 23 patients in the erlotinib and GC chemotherapy arms, respectively, had a major pathologic response. Median PFS was significantly longer with erlotinib (21.5 months) versus GC chemotherapy (11.4 months; hazard ratio, 0.39; 95% CI, 0.23 to 0.67; P < .001). Observed adverse events reflected those most commonly seen with the two treatments. CONCLUSION: The primary end point of ORR with 42 days of neoadjuvant erlotinib was not met, but the secondary end point PFS was significantly improved.

Survival After Induction Chemotherapy and Esophagectomy Is Not Improved by Adjuvant Chemotherapy.

BACKGROUND: It remains unclear whether postoperative chemotherapy improves survival among patients with esophageal squamous cell carcinoma who have undergone preoperative chemotherapy and radical resection. METHODS: Patients treated between January 2000 and December 2016 were reviewed. Eligible patients were divided into two groups: perioperative chemotherapy (preoperative and postoperative chemotherapy) and neoadjuvant chemotherapy only. The primary endpoint was disease-free survival; the secondary endpoints were overall survival and toxicities attributable to postoperative chemotherapy. To minimize the effect of patient heterogeneity between the two groups, we used propensity score matching. The survival analysis was performed using univariate analysis and a multivariable Cox regression model. RESULTS: In total, 252 patients were included in the study. Most were men (208 of 252; 82.5%); median age was 59 years. The follow-up rate was 93.3%. Age, performance status, minimally invasive surgery, and Clavien-Dindo classification were statistically different between the groups (P <.05). After propensity score matching, each group had 59 patients. Five-year disease-free survival (52.4% vs 43.6%, P = .372) and overall survival (68.6% vs 62.4%, P = .359) were not statistically different between the neoadjuvant chemotherapy group and the perioperative chemotherapy group. Cox regression identified both pathologic nodal stage and tumor regression grade are independent prognostic factors for disease-free survival and overall survival (P < .05); adjuvant chemotherapy did not influence disease-free survival (hazard ratio 1.049, 95% confidence interval, 0.587 to 1.876, P = .872) or overall survival (hazard ratio 1.297; 95% confidence interval, 0.606 to 2.775, P = .504). In the perioperative chemotherapy group, 8.5% of patients (5 of 59) had grade 3 or greater toxicity. CONCLUSIONS: Adjuvant chemotherapy is not indicated for patients with locally advanced esophageal squamous cell carcinoma after neoadjuvant platinum-based chemotherapy and surgery.

Preemptive one lung ventilation enhances lung collapse during thoracoscopic surgery: A randomized controlled trial.

In routine practice, one lung ventilation (OLV) is initiated upon pleural opening. We conducted a randomized controlled trial to compare lung collapse after preemptive OLV versus conventional OLV in thoracoscopic surgery. A total of 67 patients were enrolled (34 with conventional OLV; 33 with preemptive OLV). Preemptive OLV was conducted by closing the DLT lumen to the non-ventilated lung immediately upon assuming the lateral position with the distal port closed to the atmosphere until pleural opening (>6 minutes in all cases). Lung collapse was assessed at 1, 5, 10, 20, 30 and 40 minutes after pleural opening using a 10-point rating scale (10: complete collapse). The primary end point was the duration from pleural opening to satisfactory lung collapse (score of 8). Secondary end points included PaO2 and hypoxemia. The duration from pleural opening to satisfactory lung collapse was shorter in the preemptive OLV group (9.1 ± 1.2 vs. 14.1 ± 4.7 minutes, P < 0.01). PaO2 was comparable between the two groups prior to anesthetic induction (T0), and 20 (T2), 40 minutes (T3) after pleural incision, but was lower in the preemptive OLV group at zero minutes after pleural incision (T1) (457.5 ± 19.0 vs. 483.1 ± 18.1 mmHg, P < 0.01). No patients in either group developed hypoxemia. In summary, preemptive OLV expedites lung collapse during thoracoscopic surgery with minimal safety concern.

[Diagnostic Utility of Virtual Bronchoscopic Navigation Assisted Endobronchial 
Ultrasonography with Guide Sheath for Peripheral Pulmonary Lesions].

BACKGROUND: Virtual bronchoscopic navigation (VBN) assisted endobronchial ultrasonography with guide sheath (EBUS-GS) has reduced the difficulty and even avoiding radiation exposure during performing transbronchus lung biopsy (TBLB). To evaluate the feasibility and safety of virtual bronchoscopic navigation assisted endobronchial ultrasonography with guide sheath for peripheral pulmonary lesions. METHODS: We performed a retrospective analysis of the patients with PPLs who received VBN assisted EBUS-GS-TBLB in Peking University Cancer Hospital from January 2016 to December 2017. Their clinicopathologic data and complications were assessed. RESULTS: A total of 121 patients were enrolled in the study. The patients included 65 men and 56 women, with a mean age of (58.8±10.3) years. A total of 121 PPLs were examined, and 108 lesions of which could be detected by EBUS. The overall diagnostic yield of EBUS-GS was 73.5%. The diagnostic yield of malignancy was 82.5%. The combination of transbronchial lung biopsy, brush smear and bronchoalveolar lavage fluid provided the greatest diagnostic yield (χ²=6.084, P=0.014). Factors that significantly affected and predicted diagnostic success were EBUS probe within the lesions (χ²=20.372, P=0.000) and PPLs located in the central two-thirds of the lung (χ²=10.810, P=0.001). 1 patient (0.8%) suffered from intraoperative bleeding which could be managed under endoscopy. CONCLUSIONS: VBN assisted EBUS-GS-TBLB for PPLs was an effective and safe procedure.