Induction Chemoradiation and Surgical Resection for Superior Sulcus Non–Small-Cell Lung Carcinomas: Long-Term Results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160)

2007 ◽  
Vol 25 (3) ◽  
pp. 313-318 ◽  
Author(s):  
Valerie W. Rusch ◽  
Dorothy J. Giroux ◽  
Michael J. Kraut ◽  
John Crowley ◽  
Mark Hazuka ◽  
...  
Keyword(s):  
Cox Regression ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Complete Resection ◽  
Small Cell ◽  
Long Term Results ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Superior Sulcus

PurposeTraditional treatment for superior sulcus non–small-cell lung cancers (SS NSCLC), radiation plus surgery, yields a 50% rate of complete resection and a 30% 5-year survival. On the basis of improved outcomes in other subsets of stage III NSCLC, this trial tested the feasibility of induction chemoradiotherapy for SS NSCLC.Patients and MethodsPatients with T3-4, N0-1 SS NSCLC received two cycles of cisplatin and etoposide concurrently with radiation (45 Gy). Patients with stable or responding disease underwent thoracotomy. All patients received two more cycles of chemotherapy. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed by Cox regression analysis.ResultsFrom April 1995 to November 1999, 110 eligible patients (76 men, 34 women) were entered onto the study (78 T3, 32 T4 tumors). Induction therapy was completed by 104 (95%) patients. Of 95 patients eligible for surgery, 88 (80%) underwent thoracotomy, two (1.8%) died postoperatively, and 83 (76%) had complete resection. Pathologic complete response (CR) or minimal microscopic disease was seen in 61 (56%) resection specimens. Five-year survival was 44% for all patients and 54% after complete resection, with no difference between T3 and T4 tumors. Pathologic CR led to better survival than when any residual disease was present (P = .02). Disease progression occurred mainly in distant sites.ConclusionThis combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.

Long-Term Results of Combined-Modality Therapy in Resectable Non–Small-Cell Lung Cancer

2002 ◽  
Vol 20 (8) ◽  
pp. 1989-1995 ◽  
Author(s):  
Jocelyne Martin ◽  
Robert J. Ginsberg ◽  
Ennapadam S. Venkatraman ◽  
Manjit S. Bains ◽  
Robert J. Downey ◽  
...  
Keyword(s):  
Combined Modality Therapy ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Complete Resection ◽  
Small Cell ◽  
Long Term Results ◽  
Small Cell Lung ◽  
Combined Modality

PURPOSE: Assessment of long-term results of combined-modality therapy for resectable non–small-cell lung cancer is hampered by insufficient follow-up and small patient numbers. To evaluate this, we reviewed our collective experience. PATIENTS AND METHODS: This study was a retrospective chart review recording demographics, tumor stage, treatment, and outcome of consecutive patients undergoing surgery. Survival was analyzed by Kaplan-Meier, and prognostic factors were analyzed by log-rank and Cox regression. RESULTS: From January 1993 to December 1999, 470 patients were treated, with follow-up in 446: 27 stage I, 55 stage II, 316 stage III, 43 stage IV (solitary M1), and five uncertain. Chemotherapy was mitomycin/vinblastine/cisplatin (174 patients [39.0%]), carboplatin/paclitaxel (148 [33.2%]), and other combination (124 [27.8%]); 75 patients (16.8%) received induction radiation. Resection was complete in 77.4%, incomplete in 8.3%, attempted but with gross residual disease afterward in 1.8%, and not performed in 12.6%. Pathologic complete response occurred in 20 patients (4.5%). With median follow-up of 31.0 months for patients still alive, median and 3-year survival for pathologic stages 0, I, II, III, and IV were more than 90 months, 73%; 42 months, 52%; 23 months, 35%; 16 months, 28%; and 16 months, 23% (P < .001). In a multivariate analysis, age, complete resection, pathologic stage, and pneumonectomy, but not induction regimen, significantly influenced survival. CONCLUSION: Although pathologic complete response outside the protocol setting is low, survival of this large patient cohort is comparable to that of patients in published combined-modality trials. Survival is significantly influenced by patient age, complete resection, pathologic stage, and pneumonectomy. These results can help guide standard clinical practice and emphasize the need for novel induction regimens.

Phase II Trial of Preoperative Chemoradiotherapy Followed by Surgical Resection in Patients With Superior Sulcus Non–Small-Cell Lung Cancers: Report of Japan Clinical Oncology Group Trial 9806

2008 ◽  
Vol 26 (4) ◽  
pp. 644-649 ◽  
Author(s):  
Hideo Kunitoh ◽  
Harubumi Kato ◽  
Masahiro Tsuboi ◽  
Taro Shibata ◽  
Hisao Asamura ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Survival Rates ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Preoperative Chemoradiotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Lung Cancers ◽  
Superior Sulcus ◽  
Boost Radiotherapy

PurposeTo evaluate the safety and efficacy of preoperative chemoradiotherapy followed by surgical resection for superior sulcus tumors (SSTs).Patients and MethodsPatients with pathologically documented non–small-cell lung cancer with invasion of the first rib or more superior chest wall were enrolled as eligible; those with distant metastasis, pleural dissemination, and/or mediastinal node involvement were excluded. Patients received two cycles of chemotherapy every 4 weeks as follows; mitomycin 8 mg/m2on day 1, vindesine 3 mg/m2on days 1 and 8, and cisplatin 80 mg/m2on day 1. Radiotherapy directed at the tumor and the ipsilateral supraclavicular nodes was started on day 2 of each course, at the total dose of 45 Gy in 25 fractions, with a 1-week split. Thoracotomy was undertaken 2 to 4 weeks after completion of the chemoradiotherapy. Those with unresectable disease received boost radiotherapy.ResultsFrom May 1999 to November 2002, 76 patients were enrolled, of whom 20 had T4 disease; 75 patients were fully assessable. Chemoradiotherapy was generally well tolerated. Fifty-seven patients (76%) underwent surgical resection, and pathologic complete resection was achieved in 51 patients (68%). There were 12 patients with pathologic complete response. Major postoperative morbidity, including chylothorax, empyema, pneumonitis, adult respiratory distress syndrome, and bleeding, was observed in eight patients. There were three treatment-related deaths, including two deaths owing to postsurgical complications and one death owing to sepsis during chemoradiotherapy. The disease-free and overall survival rates at 3 years were 49% and 61%, respectively; at 5 years, they were 45% and 56%, respectively.ConclusionThis trimodality approach is safe and effective for the treatment of patients with SSTs.

Clinical Prediction of Pathologic Complete Response in Superior Sulcus Non-Small Cell Lung Cancer

2016 ◽  
Vol 101 (1) ◽  
pp. 211-217 ◽  
Author(s):  
Mara B. Antonoff ◽  
Wayne L. Hofstetter ◽  
Arlene M. Correa ◽  
Jennifer M. Bell ◽  
Boris Sepesi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Small Cell ◽  
Clinical Prediction ◽  
Small Cell Lung ◽  
Superior Sulcus

Efficacy and toxicity hypofractionated radiotherapy for centrally located non-small cell lung cancer

2021 ◽  
pp. 1-4
Author(s):  
Tanzeel Janjua ◽  
Fei Sun ◽  
Katy Clarke ◽  
Pete Dickinson ◽  
Kevin Franks ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Early Stage ◽  
Performance Status ◽  
Small Cell ◽  
Small Cell Lung ◽  
Early Stage Lung Cancer ◽  
Cox Regression Analysis

Abstract Aim: Centrally located early-stage non-small cell lung cancer in patients who are unfit for surgery are treated with fractionated radiotherapy. We present the outcomes of a moderately hypofractionated accelerated dose regimen of 50 Gy in 15 fractions from a single centre in the UK. Materials and methods: Electronic case notes and radiotherapy records of lung cancer patients treated between January 2014 and December 2016 were retrospectively reviewed. Adult Comorbidity Evaluation-27 score was used to evaluate comorbidities. Mean lung doses and percentage of lung receiving more than 20 Gy were calculated for all patients. Survival outcomes were estimated using Kaplan–Meier curves. Results: Fifty-three patients were included in the study; the median follow-up was 20.2 months. 87% of patients had stage I disease. There was no 30-day post-treatment mortality. Ninety-day mortality rate after radiotherapy was 3.8%. Grade 2 pneumonitis was seen in five patients while no grade 3 or 4 pneumonitis was observed. The median progression-free survival (PFS) and overall survival (OS) were 18.5 months and 28.2 months, respectively. The estimated 1 and 2 years PFS were 62.3% and 41.3%, respectively, and OS were 77.4% and 56.6%, respectively. Worsening performance status was associated with worse survival on cox regression analysis. Disease relapsed in 36% of patients. 7.5% of patients with relapsed disease had infield recurrence. Findings: 50 Gy in 15 fractions radiotherapy for central early-stage lung cancer is a feasible choice that requires further randomised trials.

Factors Predictive of Distant Metastases in Patients With Breast Cancer Who Have a Pathologic Complete Response After Neoadjuvant Chemotherapy

2005 ◽  
Vol 23 (28) ◽  
pp. 7098-7104 ◽  
Author(s):  
Ana M. Gonzalez-Angulo ◽  
Sean E. McGuire ◽  
Thomas A. Buchholz ◽  
Susan L. Tucker ◽  
Henry M. Kuerer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Regression Analysis ◽  
Neoadjuvant Chemotherapy ◽  
Distant Metastasis ◽  
Cox Regression ◽  
Clinical Stage ◽  
Pathologic Complete Response ◽  
Distant Metastases ◽  
Complete Response ◽  
Cox Regression Analysis

Purpose To identify clinicopathological factors predictive of distant metastasis in patients who had a pathologic complete response (pCR) after neoadjuvant chemotherapy (NC). Methods Retrospective review of 226 patients at our institution identified as having a pCR was performed. Clinical stage at diagnosis was I (2%), II (36%), IIIA (27%), IIIB (23%), and IIIC (12%). Eleven percent of all patients were inflammatory breast cancers (IBC). Ninety-five percent received anthracycline-based chemotherapy; 42% also received taxane-based therapy. The relationship of distant metastasis with clinicopathologic factors was evaluated, and Cox regression analysis was performed to identify independent predictors of development of distant metastasis. Results Median follow-up was 63 months. There were 31 distant metastases. Ten-year distant metastasis-free rate was 82%. Multivariate Cox regression analysis using combined stage revealed that clinical stages IIIB, IIIC, and IBC (hazard ratio [HR], 4.24; 95% CI, 1.96 to 9.18; P < .0001), identification of ≤ 10 lymph nodes (HR, 2.94; 95% CI, 1.40 to 6.15; P = .004), and premenopausal status (HR, 3.08; 95% CI, 1.25 to 7.59; P = .015) predicted for distant metastasis. Freedom from distant metastasis at 10 years was 97% for no factors, 88% for one factor, 77% for two factors, and 31% for three factors (P < .0001). Conclusion A small percentage of breast cancer patients with pCR experience recurrence. We identified factors that independently predicted for distant metastasis development. Our data suggest that premenopausal patients with advanced local disease and suboptimal axillary node evaluation may be candidates for clinical trials to determine whether more aggressive or investigational adjuvant therapy will be of benefit.

scholarly journals In Situ Overexpression of Matricellular Mechanical Proteins Demands Functional Immune Signature and Mitigates Non-Small Cell Lung Cancer Progression

2021 ◽  
Vol 12 ◽  
Author(s):  
Lygia Bertalha Yaegashi ◽  
Camila Machado Baldavira ◽  
Tabatha Gutierrez Prieto ◽  
Juliana Machado-Rugolo ◽  
Ana Paula Pereira Velosa ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Cox Regression ◽  
Cytotoxic T Cells ◽  
Small Cell ◽  
Malignant Cells ◽  
Pathological Stage ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Cox Regression Analysis

Non-small cell lung carcinoma (NSCLC) is a complex cancer biome composed of malignant cells embedded in a sophisticated tumor microenvironment (TME) combined with different initiating cell types, including immune cells and cancer-associated fibroblasts (CAFs), and extracellular matrix (ECM) proteins. However, little is known about these tumors’ immune-matricellular relationship as functional and mechanical barriers. This study investigated 120 patients with NSCLC to describe the immune-matricellular phenotypes of their TME and their relationship with malignant cells. Immunohistochemistry (IHC) was performed to characterize immune checkpoints (PD-L1, LAG-3, CTLA-4+, VISTA 1), T cells (CD3+), cytotoxic T cells (CD8+, Granzyme B), macrophages (CD68+), regulatory T cells (FOXP3+, CD4+), natural killer cells (CD57+), and B lymphocytes (CD20+), whereas CAFs and collagen types I, III, and V were characterized by immunofluorescence (IF). We observed two distinct functional immune-cellular barriers—the first of which showed proximity between malignant cells and cytotoxic T cells, and the second of which showed distant proximity between non-cohesive nests of malignant cells and regulatory T cells. We also identified three tumor-associated matricellular barriers: the first, with a localized increase in CAFs and a low deposition of Col V, the second with increased CAFs, Col III and Col I fibers, and the third with a high amount of Col fibers and CAFs bundled and aligned perpendicularly to the tumor border. The Cox regression analysis was designed in two steps. First, we investigated the relationship between the immune-matricellular components and tumor pathological stage (I, II, and IIIA), and better survival rates were seen in patients whose tumors expressed collagen type III &gt; 24.89 fibers/mm². Then, we included patients who had progressed to pathological stage IV and found an association between poor survival and tumor VISTA 1 expression &gt; 52.86 cells/mm² and CD3+ ≤ 278.5 cells/mm². We thus concluded that differential patterns in the distribution of immune-matricellular phenotypes in the TME of NSCLC patients could be used in translational studies to predict new treatment strategies and improve patient outcome. These data raise the possibility that proteins with mechanical barrier function in NSCLC may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction, which can otherwise be targeted effectively with immunotherapy or collagen therapy.

Safety and Feasibility of Thoracoscopic Lung Resection for Non-Small-Cell Lung Cancer in Octogenarians

2020 ◽  
pp. 155698452097162
Author(s):  
Xiaoying Lou ◽  
Andrew Sanders ◽  
Kaustubh Wagh ◽  
Jose N. Binongo ◽  
Manu Sancheti ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cox Regression ◽  
Lung Resection ◽  
Small Cell ◽  
Small Cell Lung ◽  
Preoperative Risk ◽  
Term Survival ◽  
Long Term Survival ◽  
Cox Regression Analysis

Objective Octogenarians comprise an increasing proportion of patients presenting with non-small-cell lung cancer (NSCLC). This study examines postoperative morbidity and mortality, and long-term survival in octogenarians undergoing thoracoscopic anatomic lung resection for NSCLC, compared with younger cohorts. Methods We conducted a retrospective review of our institutional Society of Thoracic Surgeons General Thoracic Surgery Database of all patients ≥60 years old undergoing elective lobectomy or segmentectomy for pathologic stage I, II, and IIIA NSCLC between 2009 and 2018. Results were compared between octogenarians ( n = 71) to 2 younger cohorts of 60- to 69-year-olds ( n = 359) and 70- to 79-year-olds ( n = 308). Long-term survival among octogenarians was graphically summarized using the Kaplan–Meier method. Cox regression analysis was used to identify preoperative risk factors for mortality. Results A greater proportion of octogenarians required intensive care unit admission and discharge to extended-care facilities; however, postoperative length of stay was similar between groups. Among postoperative complications, arrhythmia and renal failure were more likely in the older cohort. Compared to the youngest cohort, in-hospital and 30-day mortality were highest among octogenarians. Overall survival among octogenarians at 1, 3, and 5 years was 87.3%, 61.8%, and 50.5%, respectively. On multivariable Cox regression analysis of baseline demographic variables, presence of stroke (hazard ratio [HR] = 28.5, 95% confidence interval [CI]: 6.1 to 132.7, P < 0.001) and coronary artery disease (HR = 2.5, 95% CI: 1.2 to 5.3, P = 0.02) were significant predictors of overall mortality among octogenarians. Conclusions Thoracoscopic resection can be performed with favorable early postoperative outcomes among octogenarians. Long-term survival, although comparable to their healthy peers, is worse than those of younger cohorts. Further study into preoperative risk stratification and alternative therapies among octogenarians is needed.

scholarly journals Serum miR-1228-3p and miR-181a-5p as Noninvasive Biomarkers for Non-Small Cell Lung Cancer Diagnosis and Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wei-Xiao Xue ◽  
Meng-Yu Zhang ◽  
Rui Li ◽  
Xiao Liu ◽  
Yun-Hong Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Roc Analysis ◽  
Cox Regression ◽  
Small Cell ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis ◽  
Noninvasive Biomarkers ◽  
Nsclc Patients

Background. Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods. A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs’ target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription– quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results. A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P =0.006) and miR-181a-5p (P =0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563–0.806; P =0.006) and 0.647 (95% CI, 0.506–0.758; P =0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593–0.828; P =0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions. Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.

A new measurement of residual cancer burden to predict survival after neoadjuvant chemotherapy

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 536-536 ◽  
Author(s):  
W. Symmans ◽  
F. Peintinger ◽  
C. Hatzis ◽  
H. Kuerer ◽  
V. Valero ◽  
...  
Keyword(s):  
Neoadjuvant Chemotherapy ◽  
Cox Regression ◽  
Residual Disease ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Continuous Measure ◽  
Residual Cancer ◽  
Cancer Burden ◽  
Residual Cancer Burden ◽  
Ajcc Stage

536 Background: The strength of association between tumor response and survival is critical for neoadjuvant chemotherapy trials. Pathologic complete response (pCR) reliably predicts survival benefit, but residual disease contains a range of pathologic responses that likely contain different prognostic groups, including near complete response and resistance. Methods: Pathologic slides and reports were reviewed from 432 patients in two completed neoadjuvant trials: 1) fluorouracil, doxorubicin and cyclophosphamide (FAC) in 189 patients, and 2) paclitaxel followed by FAC (T/FAC) in 243 patients. Paclitaxel was administered as twelve weekly (n=126) or four 3-weekly cycles (n=117). Residual cancer burden (RCB) was calculated as an index that combines pathologic measurements of primary tumor (size and cellularity) and nodal metastases (number and size). We compared four RCB categories, from RCB-0 (pCR) to RCB-3 (chemoresistant), and post-treatment revised AJCC Stage (0-III) for prediction of distant relapse-free survival (DRFS) in multivariate Cox regression analyses (stratified by ER status). Results: The pCR rate was greater after T/FAC than FAC (24% vs. 16%, LR p<0.05), and after weekly (vs. 3-weekly) paclitaxel in T/FAC (30% vs. 16%, LR p<0.01). In patients with residual disease, RCB measurements were significantly lower after T/FAC than FAC (t-test, p<0.0001), but were not different between paclitaxel schedules in T/FAC. RCB was a continuous predictor of DRFS after T/FAC (HR=1.86, 95%CI 1.51–2.30) or FAC (HR=1.67, CI 1.38–2.01) with median follow-up 5 and 8 years, respectively. The resistant category RCB-3 predicted relapse more strongly than AJCC Stage III and identified a larger group of high-risk patients ( Table ). Conclusions: RCB is a new continuous measure of pathologic response that is defined from routine pathologic materials, represents the distribution of residual disease, is a significant predictor of DRFS, and defines chemotherapy resistance more effectively than revised AJCC Stage. [Table: see text] [Table: see text]

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