Primary tumor resection of non-small cell lung cancer patients with ipsilateral pleural dissemination (M1a) in the era of targeted therapy.
ABSTRACT: BACKGROUND:Non-small cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination (M1a) are generally contraindicated for surgery. Recently, several studies have demonstrated that these patients might benefit from primary tumor resection (PTR). However, whether PTR is beneficial for driver oncogene-positive patients treated with targeted therapy, remains unclear. Here, we investigated the effects of PTR on survival in the era of targeted therapy. METHODS:In total, 105 NSCLC patients with ipsilateral pleural dissemination were identified. The mode of systemic treatment was assessed in this study. Survival analysis was performed with the Kaplan-Meier method and Cox proportional hazards regression. The overall survival (OS) of patients with or without PTR was compared between propensity score-matched groups (caliper: 0.02). RESULTS:In the entire cohort, PTR was associated with improved OS in both unmatched (median survival time [MST]: 50.0 vs. 29.6?months, P = 0.019) and matched (MST: 50.0 vs. 34.4?months, P = 0.052) cohorts. Multivariate regression models showed that surgery was an independent favorable prognostic factor for OS. A total of 70 patients underwent genetic testing, and targeted therapies, such as EGFR-TKIs or ALK-TKIs, were used in the driver oncogene-positive patients. Subgroup analysis showed that PTR did not improve OS in the targeted therapy group (MST: 57.1 months vs. 50.4?months, P = 0.840). However, surgery significantly prolonged survival in the nontargeted therapy group (MST: 39.8 vs. 14.2?months, P = 0.002). CONCLUSIONS:The results of this study indicated that PTR could prolong OS in stage IV NSCLC patients with ipsilateral pleural dissemination, especially in patients who are not candidates for targeted therapy. KEY POINTS:Non-small cell lung cancer patients with ipsilateral pleural dissemination can benefit from primary tumor resection. Primary tumor resection could prolong overall survival (OS) in non-small cell lung cancer patients with ipsilateral pleural dissemination who are not candidates for targeted therapy.
Project description:<h4>Background</h4>Non-small-cell lung cancer (NSCLC) patients with ipsilateral pleural dissemination are defined as M1a in the eighth of American Joint Committee on Cancer (AJCC) TNM staging. We aimed to build a nomogram to predict lung cancer specific survival (LCSS) of NSCLC patients with ipsilateral pleural dissemination and to compare the impact of primary tumor resection (PTR) on LCSS among patients with different features.<h4>Methods</h4>A total of 3,918 NSCLC patients with ipsilateral pleural dissemination were identified from the Surveillance, Epidemiology, and End Results (SEER) database. We selected and integrated significant prognostic factors based on competing risk regression to build a nomogram. The model was subjected to internal validation within SEER cohort and external validation with the cohort of 97 patients from Peking University People's Hospital.<h4>Results</h4>Age (<i>P</i> < 0.001), gender (<i>P</i> = 0.037), T stage (<i>P</i> = 0.002), N stage (<i>P</i> < 0.001), metastasis pattern (<i>P</i> = 0.005), chemotherapy (<i>P</i> < 0.001), and PTR (<i>P</i> < 0.001) were independent prognostic factors. The calibration curves presented a good consistency and the Harrell's C-index of nomogram were 0.682 (95%CI: 0.673-0.691), 0.687 (95%CI: 0.670-0.704) and 0.667 (95%CI: 0.584-0.750) in training, internal, and external validation cohort, respectively. Interaction tests suggested a greater LCSS difference caused by PTR in patients without chemotherapy (P < 0.001).<h4>Conclusions</h4>We developed a nomogram based on competing risk regression to reliably predict prognosis of NSCLC patients with ipsilateral pleural dissemination and validated this nomogram in an external Chinese cohort. This novel nomogram might be a practical tool for clinicians to anticipate the 1-, 3- and 5-year LCSS for NSCLC patients with pleural dissemination. Subgroup analysis indicated that patients without chemotherapy could get more benefit from PTR. In order to assess the role of PTR in the management of M1a patients more accurately, further prospective study would be urgently required.
Project description:<h4>Background</h4>Primary tumor resection (PTR) as a treatment option for patients with stage IV pancreatic cancer (PC) is controversial.<h4>Patients and methods</h4>Stage IV PC patients, with treatment data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER), were screened. The main outcomes were overall survival (OS) and cancer-specific survival (CSS).<h4>Results</h4>We enrolled 15,836 stage IV PC patients in this study. Propensity score-matched analyses revealed improved OS and CSS of patients receiving chemotherapy plus PTR versus chemotherapy (median survival time [MST<sub>OS</sub> ]: 13 vs. 9 months, p = 0.024; MST<sub>CSS</sub> : 14 vs. 10 months, p = 0.035), and chemoradiotherapy plus PTR versus chemoradiotherapy (MST<sub>OS</sub> : 14 vs. 7 months, p = 0.044; MST<sub>CSS</sub> : 14 vs. 7 months, p = 0.066). Multivariate adjusted analyses further confirmed these results. Stratified with different metastatic modalities, multivariate analyses suggested that PTR significantly improved the OS and CSS among patients with ≤1 metastatic organ, and that patients with brain metastasis might not benefit from chemotherapy treatment.<h4>Conclusion</h4>PTR improves the OS and CSS of stage IV PC patients on the basis of chemotherapy or chemoradiotherapy, provided that the metastases involve ≤1 organ. Chemotherapy, however, should be carefully considered in patients with metastases involving the brain.
Project description:<h4>Background</h4>Whether patients with non-small cell lung cancer (NSCLC) with unexpected pleural dissemination (UPD) could get survival benefit from tumor resection remained controversial.<h4>Methods</h4>Totally, 169 patients with NSCLC with UPD were included between 2012 and 2016. Patients were divided into the tumor resection and open-close group. Progression-free survival (PFS) and overall survival (OS) were compared with a log-rank test. The multivariable Cox analysis was applied to identify prognostic factors.<h4>Results</h4>Sixty-five patients received open-close surgery and 104 patients underwent main tumor and visible pleural nodule resection. Tumor resection significantly prolonged OS (hazard ratio [HR]: 0.408, P < 0.001), local PFS (HR: 0.283, P < 0.001), regional PFS (HR: 0.506, P = 0.005), and distant metastasis (HR: 0.595, P = 0.032). Multivariable Cox analysis confirmed that surgical method was an independent prognostic factor for OS, local PFS and regional PFS, except distant metastasis. Subgroup analyses indicated that tumor resection could not improve OS in the patients who received targeted therapy (HR: 0.649, P = 0.382), however, tumor resection was beneficial for the patients who received adjuvant chemotherapy alone (HR: 0.322, P < 0.001). In the tumor resection group, lobectomy (HR: 0.960, P = 0.917) and systematic lymphadenectomy (HR: 1.512, P = 0.259) did not show survival benefit for OS.<h4>Conclusions</h4>Main tumor and visible pleural nodule resection could improve prognosis in patients with UPD who could not receive adjuvant targeted therapy. Sublobar resection without systematic lymphadenectomy may be the optimal procedure.
Project description:<h4>Background</h4>The role of primary tumor resection in occult M1a lung adenocarcinoma remains unclear, especially for patients receiving targeted therapy. The purpose of this study is to assess the effect of primary tumor resection on overall survival (OS) in lung adenocarcinoma patients with occult pleural disseminations receiving targeted therapy.<h4>Methods</h4>Lung adenocarcinoma patients with intraoperatively-confirmed occult pleural dissemination (M1a), who hospitalized in the Department of Thoracic Surgery in Fudan Shanghai Cancer Center from May 2008 to December 2017 and received EGFR-TKIs therapy, were enrolled. Log-rank tests were used to compare the survival differences between groups.<h4>Results</h4>34 patients receiving EGFR-TKIs were enrolled. The majority of them were never smokers (29/34, 85.3%). Among the enrolled patients, 20 (58.8%) patients underwent primary tumor resection, while 14 (41.2%) patients not. There was no distributional difference of baselines between patients undergoing and not undergoing primary tumor resection. Further analyses demonstrated that the patients undergoing primary tumor resection had a prolonged OS compared with those not (log-rank <i>P</i>= 0.042). The 2-year and 5-year OS for patients receiving primary tumor resection and EGFR-TKIs was 90.0% and 60.1%.<h4>Conclusions</h4>Primary tumor resection was associated with improved survival in patients with occult intraoperatively-confirmed M1a adenocarcinoma receiving EGFR-TKIs.
Project description:<h4>Background</h4>Previous studies comparing primary tumor resection (PTR) to palliative treatment for advanced-stage pancreatic ductal adenocarcinoma (PDA) were limited by strong selection bias. We used multiple methods to control for confounding and selection bias to estimate the effect of PTR on survival for late-stage PDA.<h4>Methods</h4>Surveillance, Epidemiology, and End Results (SEER) 18 registry database for 2004 through 2014 was retrieved for the present study. A total of 4322 patients with stage III (AJCC, 6th) PDA were included in this study. Propensity score matching (PSM) was performed to eliminate possible bias. In addition, instrumental variable (IV) analysis was utilized to adjust for both measured and unmeasured confounders.<h4>Results</h4>A total of 4322 patients with stage III PDA including 552 (12.8%) who underwent PTR, 3770 (87.2%) without PTR, were identified. In the multivariable cohort, a clear prognostic advantage of PTR was observed in overall survival (OS) (P?<?0.001) and disease-specific survival (DSS) (P?<?0.001) compared to patients after non-surgery therapy. In the PSM cohort, patients in PTR group showed a better OS and DSS (both P values <?0.001) compared to patients in non-surgery group. The survival benefit of PTR for stage III PDA was not observed in the two-stage residual inclusion (2SRI) model. Estimates based on this instrument indicated that patients treated with PTR had similar OS (P?=?0.448) and DSS (P?=?0.719). In IV analyses stratified by chemotherapy and tumor location, patients undergoing PTR had similar OS and DSS compared to patients in non-surgery group across all subgroups.<h4>Conclusions</h4>Survival with PTR did not differ significantly from palliative treatment in marginal patients with stage III pancreatic adenocarcinoma. High-quality randomized trials are needed to validate these results.
Project description:BACKGROUND:The TRICC0808 trial is a phase II multi-institutional trial that investigated the efficacy of preoperative mFOLFOX6 + bevacizumab (BV) therapy for liver-only metastasis that is unsuitable for upfront resection. The R0 resection rate in the efficacy analysis has been reported to be 44.4%, and the final analysis for survival was conducted (data fixation on February 16, 2015). METHODS:Six cycles of mFOLFOX6 + BV therapy were applied to patients with liver-only metastases, which were > 5 cm in diameter or more than four tumors (H2 and H3), and hepatectomy was performed if possible. Primary and secondary endpoints were the R0 hepatectomy rate and overall survival (OS), respectively. RESULTS:Of 46 patients registered, OS was analyzed for 45 patients in whom the 3-year OS rate from the starting date of chemotherapy was 44.0% with a 33.6-month median survival time (MST). The 3-year OS rate of 31 patients with hepatectomy, including resection after an additional chemotherapy, was 61.3% with a 43.1-month MST, which was significantly better than 0% of the 3-year OS rate with a 21.0-month MST of 14 patients without hepatectomy (p value < 0.0001). In 24 patients who underwent hepatectomy after six cycles of protocol chemotherapy, the 3-year relapse-free survival rate was 8.3%, with a 36.8-month MST. CONCLUSIONS:This final analysis of the TRICC0808 trial revealed a better long-term survival in patients with hepatectomy after mFOLFOX6 + BV therapy, although most examined patients eventually developed recurrence. Thus, hepatectomy after chemotherapy might improve the survival in patients with advanced liver metastases, although cure remains difficult.
Project description:Gram-negative bacterial infections, especially multidrug-resistant (MDR) bacterial infection, are becoming a serious threat to public health. Although it is widely accepted that both appropriate initial empirical therapy and targeted therapy are important, but for patients needing therapy adjustment, few studies have explored whether adjustment strategy based on microbiologic susceptibility test (MST) brings better outcome compared with empirical adjustment.A total of 320 patients with gram-negative bacterial infection (airway, blood, or pleural effusion) were selected and a prospective cohort study was conducted. Baseline characteristics and outcomes (microbiologic, clinical, and economic) were documented during follow-up.MDR and nosocomial infections were common among subjects. Initial therapies consistent with MST could result in reduced in-hospital mortality, treatment failure rate, infection-related death, percentages of patients needing therapy adjustment, and daily hospitalization cost with increased successful treatment rate compared with inconsistent with MST, and microbiologic outcomes were also better with appropriate therapies.For patients needing therapy adjustment, relying on MST gained no significant benefit on mortality, clinical, or microbiologic outcomes compared with depending on clinical experience. But for patients with MDR infection, adjustment relying on MST gained more benefit than non-MDR infection.Appropriate initial therapy significantly improved the prognosis of patients with gram-negative bacterial infections, but improvement was not that obvious for patients needing therapy adjustment which was based on MST compared with clinical experience, and more beneficial effects of adjustment relying on MST were obtained for patients with MDR bacterial infection.
Project description:<h4>Background</h4> The prognostic prolongation effect of surgical resection in the management of gastric neuroendocrine carcinoma (GNEC) with distant metastases was still uncertain. The purpose of this study was to investigate the association of primary tumor resection (PTR) with outcomes in patients with stage IV GNEC. <h4>Methods</h4> This retrospective study analyzed patients with distant metastatic GNEC diagnosed between 2000 and 2018 and identified using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were divided into PTR and non-PTR groups. The stabilized inverse probability of treatment weighting (IPTW) method was used to reduce the selection bias. Overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan–Meier method and log-rank test. Cox-regression analyses (uni- and multivariate) were performed to evaluate factors potentially influencing survival. <h4>Results</h4> A total of 126 patients with a median follow-up of 79 months were identified. Forty-four patients underwent PTR and 82 patients did not undergo surgery. After the IPTW approach, PTR improved the OS in patients with stage IV GNEC (median OS 12 vs. 6 months, P = 0.010). The 1- and 3-year OS for patients with or without PTR were 43.8% and 34.5%, and 27.9% and 6.5%, respectively. The median CSS was 12 months for patients undergoing PTR and 6 months for those who did not. The 1 and 3-year CSS for patients with or without PTR were 45.1% and 37.0%, and 27.9% and 6.5%, respectively. In IPTW-adjusted Cox proportional hazards regression analysis, PTR was recognized as an independent factor for improved survival after the occurrence of distant metastatic disease [OS: hazard ratio (HR) = 0.305; 95% confidence interval (CI): 0.196, 0.475; and CSS: HR = 0.278; 95% CI: 0.171, 0.452]. <h4>Conclusion</h4> PTR for stage IV GNEC contributes to a better prognosis compared with non-surgery. This study supported the resection of the primary tumor in patients with distant metastatic GNEC.
Project description:<h4>Objective</h4>To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation.<h4>Patients and methods</h4>Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan-Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR.<h4>Results</h4>A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0-22.0 vs 8.0, 95% CI: 5.0-11.0 for median OS; 22.0, 95% CI: 13.0-33.0 vs 9.0, 95% CI: 5.0-11.0 for median CSS; both log-rank <i>P</i><0.001). Patients receiving PTR plus chemotherapy showed better survival compared with those receiving only chemotherapy (median OS: 18, 95% CI: 13-27 vs 9.0, 95% CI: 8.0-11.0; median CSS: 23.0, 95% CI: 14.0-36.0 vs 9.0, 95% CI: 8.0-13.0; both log-rank <i>P</i><0.001).<h4>Conclusion</h4>PTR might bring a survival benefit to ampullary cancer patients with distant metastasis at the initial presentation and might provide a more favorable prognosis when combined with chemotherapy.
Project description:<h4>Background and aims</h4>Sequential therapy with molecular-targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first-line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)-related HCC.<h4>Methods</h4>We evaluated 504 HCC patients treated with SORA (Study-1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early-, mid-, and late-term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid- and late-term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study-2).<h4>Results</h4>Overall survival (OS) of HCC patients who received sequential MTA therapy after first-line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early-term group, mid-term group, and the later-time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study-1). In Study-2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin-bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA.<h4>Conclusions</h4>Sequential therapy with SORA as the first-line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.