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Clinical Impact of Supraclavicular Lymph Node Involvement of Stage IIIC Non-Small Cell Lung Cancer Patients.

ABSTRACT: Background and Objective: Investigations on the clinical impact of supraclavicular lymph node (SCN) involvement in stage IIIC non-small cell lung cancer (NSCLC) remain scarce. We evaluated the oncological outcomes of definitive radiochemotherapy and the clinical significance of SCN involvement. Materials and Methods: Between November 2009 and June 2019, a total of 40 patients with N3-positivity and NSCLC were evaluated. Most patients received concomitant chemotherapy, but six patients who received radiotherapy (RT) alone were also included. Twenty-one patients (52.5%) received 3D-conformal RT (3DCRT), and the remainder received intensity-modulated RT (IMRT). Results: The median follow-up duration was 10.7 months (range: 1.7-120.6 months). Median overall survival (OS) and cause-specific survival (CSS) times were 10.8 months and 16.3 months, respectively. Among the 40 patients, 17 (42.5%) had SCN involvement. SCN involvement negatively affected progression-free survival (hazard ratio (HR): 2.08, 95% confidence interval (CI): 1.04-4.17, p = 0.039) and local control (HR: 3.05, 95% CI: 1.09-8.50, p = 0.034). However, IMRT use was correlated with higher local control (HR: 0.28, 95% CI: 0.09-0.86, p = 0.027). Grade ≥3 esophagitis and pneumonitis accounted for 7.5% and 15.0% of all cases, respectively. A higher RT dose (mean dose: 66.6 vs. 61.7 Gy) was significantly correlated with grade ≥3 pneumonitis (p = 0.001). RT modality was a significant factor (p = 0.042, five of six cases occurred in the IMRT group). Conclusions: SCN involvement could negatively affect oncologic outcomes of stage IIIC NSCLC patients. High-dose irradiation with IMRT could increase local control but may cause lung toxicities.

SUBMITTER: Park S

PROVIDER: S-EPMC8004859 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAccurate predictions of tumor dissemination risks and medical treatment outcomes are critical to personalize therapy. Patient-derived xenograft (PDX) models in mice have demonstrated high accuracy in predicting therapeutic outcomes, but methods for predicting tumor invasiveness and early stages of vascular/lymphatic dissemination are still lacking. Here we show that a zebrafish tumor xenograft (ZTX) platform based on implantation of PDX tissue fragments recapitulate both treatment outcome and tumor invasiveness/dissemination in patients, within an assay time of only 3 days.MethodsUsing a panel of 39 non-small cell lung cancer PDX models, we developed a combined mouse-zebrafish PDX platform based on direct implantation of cryopreserved PDX tissue fragments into zebrafish embryos, without the need for pre-culturing or expansion. Clinical proof-of-principle was established by direct implantation of tumor samples from four patients.ResultsThe resulting ZTX models responded to Erlotinib and Paclitaxel, with similar potency as in mouse-PDX models and the patients themselves, and resistant tumors similarly failed to respond to these drugs in the ZTX system. Drug response was coupled to elevated expression of EGFR, Mdm2, Ptch1 and Tsc1 (Erlotinib), or Nras and Ptch1 (Paclitaxel) and reduced expression of Egfr, Erbb2 and Foxa (Paclitaxel). Importantly, ZTX models retained the invasive phenotypes of the tumors and predicted lymph node involvement of the patients with 91% sensitivity and 62% specificity, which was superior to clinically used tests. The biopsies from all four patient tested implanted successfully, and treatment outcome and dissemination were quantified for all patients in only 3 days.ConclusionsWe conclude that the ZTX platform provide a fast, accurate, and clinically relevant system for evaluation of treatment outcome and invasion/dissemination of PDX models, providing an attractive platform for combined mouse-zebrafish PDX trials and personalized medicine.

Project description:ObjectiveSelected patients with stage IV non-small cell lung cancer (NSCLC) who underwent primary tumor resection have witnessed a survival benefit. Whether additional lymph node dissection (LND) would result in a better effect remain unknown. We investigated the prognostic impact of LND on patients with stage IV NSCLC who received primary tumor resection (PTR).MethodsPatients with stage IV NSCLC who underwent PTR were identified from the Surveillance, Epidemiology, and End Results database from 2004 to 2016. Propensity-score matching was performed to minimize the confounding effect, and lung cancer-specific survival (CSS) and overall survival (OS) were compared after matching. Multivariable Cox regression was used to identify prognostic factors and to adjust for covariates in subgroup analysis. The effect of the number of lymph nodes examined on the CSS was evaluated by repeating the Cox analysis in a binary method.ResultsA total of 4,114 patients with stage IV NSCLC who receive surgery met our criteria, of which 2,622 (63.73%) underwent LND and 628 patients were identified 1:1 in LND and non-LND groups after matching. Compared with the non-LND group, the LND group had a longer CSS (median: 23 vs. 16 months, p < 0.001) and OS (median: 21 vs. 15 months, p < 0.001). Multivariable regression showed that LND was independently associated with favorable CCS [hazard ratio (HR) = 0.78, 95% confidence interval (CI) 0.69-0.89, P < 0.001] and OS (HR = 0.79, 95% CI 0.70-0.89, P < 0.001). Subgroup analysis suggested that LND is an independent favorable predictor to survival in the surgical patients who were older age (>60 years old), female, T3-4, N0, and M1a stage and those who underwent sublobar resection. In addition, a statistically significant CCS benefit was associated with an increasing number of lymph nodes examined through 25 lymph nodes.ConclusionsLND with a certain range of lymph nodes number examined was associated with improved survival for patients with stage IV NSCLC who received primary tumor resection. The results may have implications for guidelines on lymph nodes management in selective advanced NSCLC for surgery.

Project description:BackgroundThe current preferred approach for surgical mediastinal staging of non-small-cell lung carcinoma is video-assisted mediastinoscopy. An alternative technique in which lymph nodes are resected instead of biopsied is video-assisted mediastinoscopic lymphadenectomy (VAMLA) that is suggested to be superior in detecting N2 disease. Yet, evidence is conflicting and furthermore limited by sample size. The objective was to compare mediastinal staging through VAMLA and video-assisted mediastinoscopy.MethodsA single-center cohort study was conducted. All consecutive patients that underwent surgical mediastinal staging of non-small-cell lung carcinoma by VAMLA (2011 to 2018) were compared to historic video-assisted mediastinoscopy controls (2007 to 2011). Patients with negative surgical mediastinal staging underwent subsequent anatomical resection with systematic regional lymphadenectomy. Primary outcome was the sensitivity and negative predictive value for detecting N2 disease.ResultsTwo-hundred-sixty-nine video-assisted mediastinoscopic lymphadenectomies and 118 video-assisted mediastinoscopies were performed. The prevalence of N2 disease was 20% and 26% respectively in the VAMLA and video-assisted mediastinoscopy group, while the rate of unforeseen pN2 resulting from lymph node dissection during anatomical resection was 4% and 11%, respectively. Invasive staging using VAMLA demonstrated superior sensitivity of 0.82 and a negative predictive value of 0.96 when compared to video-assisted mediastinoscopy (0.62 and 0.89, respectively), offering a 64% decrease in risk of unforeseen pN2 following anatomical resection. However, VAMLA is also associated with a 75% risk increase on complications (P=0.36).ConclusionsWe conclude that performing invasive mediastinal lymph node assessment for staging of non-small-cell lung carcinoma, VAMLA should be the preferred technique with superior sensitivity and negative predictive value in detecting N2 disease. Though, VAMLA is also associated with an increased risk of complications.

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Clinical Impact of Supraclavicular Lymph Node Involvement of Stage IIIC Non-Small Cell Lung Cancer Patients.

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