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E. Vallieres
Moderator of
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ORAL 04 - Adjuvant Therapy for Early Stage Lung Cancer (ID 99)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 8
- Moderators:E. Vallieres, Y. Ohe
- Coordinates: 9/07/2015, 10:45 - 12:15, 205+207
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ORAL04.01 - Final Results of Phase III Trial of Adjuvant Chemo-Immunotherapy in Lung Cancer (ID 175)
10:45 - 10:56 | Author(s): H. Kimura, Y. Matsui, A. Ishikawa, T. Iizasa, M. Shingyoji, M. Nakajima, I. Yoshino
- Abstract
- Presentation
Background:
From our randomized controlled phase III trial of adjuvant chemo‑immunotherapy in lung cancer patients, the preliminary results indicated significant advantage in immunotherapy arm combined with chemotherapy. We report here the final analysis and long term results with 42.8 months of median follow up time.
Methods:
Between April 2007 and July 2012, 103 postsurgical non-small cell lung cancer patients were randomly assigned to receive either chemo-immunotherapy (group A) or chemotherapy (group B). The immunotherapy consisted of the adoptive transfer of autologous activated killer T cells and dendritic cells obtained from the lung cancer patients’ own regional lymph nodes.
Results:
The 2-year overall survival rates in groups A and B were 96.0 and 64.7 %, and the 5-year rates were 74.6 and 40.9 %, respectively, and the results confirmed the statistically significant difference analyzed 2 years previously. The hazard ratio (HR) was 0.321 (95% Confidence Interval 0.164~0.631). The 2- and 5-year recurrence-free survival rates were 68.0, 41.2 and 57.2, 29.2 % in groups A and B, respectively. Those differences were also statistically significant (log-rank test p = 0.0020). The HR was 0.435 (p = 0.0027) in favor of group A. Subgroup analysis between treatment groups using cox models indicated male (HR: 0.351, 95%CI: 0.171~0.721), Adenocarcinoma (HR: 0.279, 95%CI: 0.116~0.669), stage III (HR: 0.228, 95%CI: 0.092~0.564) and those who did not received preoperative chemotherapy had lower hazard ratio compared to other groups. Immunological analysis of cell surface markers in regional lymph-nodes of immunotherapy patients indicated the ratios of CD8 vs CD4 (CD8/4) are elevated in survivors.
Conclusion:
The final results of the statistical and immunological analysis of the study confirmed the efficacy of immunotherapy in adjuvant treatment of lung cancer patients. The study indicated the advantages and limitations of cell mediated immunotherapy and a large-scale multi-institutional RCT is inevitable for the clinical application of the study.
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- Abstract
- Presentation
Background:
Postoperative adjuvant chemotherapy is extensively received due to its extension of the time to recurrence and enhancement of survival rate in NSCLC. However, it has reached the plateau presently, the beneficial cases are few, and drug-resistance and over-treatment phenomena are in most of patients, hence it is necessary to seek new postoperative adjuvant chemotherapy to improve the survival rate. Angiogenesis is one premise of occurrence, development and metastasize of malignant tumors, but VEGF is one of the most important tumors in the process of neovascularization. Under normal conditions, VEGF is hardly expressed in a lot of normal tissues in vivo, while highly expressed in the tumors. Endostatin can significantly intervene the angiogenesis-promoting effect to block the nutritional supply for tumors and inhibit tumor proliferation or metastasis. We compare the curative effect of endostatin plus adjuvant chemotherapy and adjuvant chemotherapy alone in the treatment of patients with completely resected NSCLC at stage IB-IIIA.
Methods:
This is an open, multicenter, randomized (1:1) study, stratified by gender, stage and histology. Completely resected pts (stage IB to IIIA) were randomized to receive adjuvant NP plus Endostatin (Vinorelbine 25mg/m2 on d1 and d8 plus Cisplatin 75 mg/m2 on d1, and iv plus endostatin 7.5mg/m2 per day iv for consecutive 14 days, every 21 days as one cycle, 4 cycles in total) or NP regimen alone. The primary endpoint was disease-free survival (DFS). Secondary endpoints included tumor response rate, overall survival and safety.
Results:
250 pts (1:1) were included from 07/2007 to 06/2009. Two arms were well-balanced with regard to age, gender, histology, staging, and resection type. The follow-up time was 60 months. The two groups had no significant difference in the incidence of toxicity reaction. Endostatin plus NP can prolong the DFS of patients with completely resectable NSCLC at stage IIIA with high security, but with no statistical difference (19.33±3.73 m vs 17.10±9.68 m). Cases with high expression of VEGF showed a better DFS than cases with low expression in endostatin plus NP group (48.45±3.52m vs 40.18±4.54m, P < 0.05). The level of peripheral circulating endothelial progenitor cells (EPCs) in NSCLC patients was significantly higher than that in healthy volunteers. EPCs level was associated with NSCLC stage. The EPCs levels after treatment significantly decreased than that before treatment (P=0.014) in beneficiaries of NP or NP plus with endostatin. The time to progression (TTP) was longer in patients with lower levels of EPCs (<0.35%) before chemotherapy or endostatin treatment (P<0.001). However, no statistically significant difference in OS was noticed between the two arms (P = 0.962). The survival rate of endostatin plus NP group was higher for patients in stage IIIA NSCLC, but the differences did not reach statistical significance (MST 41.267 months vs 39.533 months, P = 0.760).
Conclusion:
Vascular targeted therapy could prolong the DFS of patients with complete resectable NSCLC in stage IIIA, but did not show benefits in OS for stage IB−IIIA. We shall develop new strategies to identify the patient subgroups that will be benefited or harmed by vascular targeted therapy.
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ORAL04.03 - Preliminary Results of the International Tailored Chemotherapy Adjuvant Trial: The ITACA Trial (ID 1262)
11:07 - 11:18 | Author(s): S. Novello, C. Grohé, M. Geissler, M.H. Serke, I. Colantonio, A. Meyer, E. Stoelben, M. Milella, W. Schuette, C. Kropf-Sanchen, G. Valmadre, R. Buosi, V. Torri, V. Monica, G.V.V. Scagliotti, M. Papotti, C. Manegold
- Abstract
Background:
In resected early stage (II-IIIA) non-small cell lung cancer (NSCLC) adjuvant chemotherapy improves overall survival but the benefit is limited and pharmacogenomics tailored treatment is a potential way to further improve outcome. A phase III multicenter randomized trial comparing adjuvant pharmacogenomics-driven chemotherapy, based on thymidylate synthase (TS) and excision-repair cross-complementing-1 (ERCC1) gene expression versus standard adjuvant chemotherapy in completely resected Stage II-IIIA NSCLC recently completed patients’ (pts) enrolment (EudraCT #: 2008-001764-36).
Methods:
The mRNA ERCC1 and TS expression by qRT-PCR was centrally assessed on paraffin-embedded, post-surgical tumor specimens in all registered pts. Immunohistochemistry (IHC) straining for ERCC1 (using 2 monoclonal antibodies, 8F1 and 4F9) and TS protein expression was also performed. Randomization was stratified by stage and smoking status. Trial was emended on February 2011 to include the 7th staging system. The primary end point of the study is overall survival; secondary end points include recurrence-free survival, therapeutic compliance, toxicity profile and comparative evaluation of ERCC1 and TS mRNA versus protein expression. Study design was already reported [Novello S et al, JTO 2013; 8 (Suppl 2) P3.12-023].
Results:
Enrolment was concluded in August 2014 and at that time all gene expression data were available. Recruitment and gene expression results were completed in August 2014. 386 pts were included in the control arm, 375 in the tailored arm and 41 were excluded as screening failures (14) or are not yet fully evaluable (27). Statistical correlations to compare treatments received, toxicity profiles and pts’ survival data in the tailored and control groups are ongoing. Further data analyses will include the correlation between biomarker ERCC1/TS mRNA and protein expression levels, as well as compare ERCC1-IHC scores with the 2 ERCC1 antibodies. The distribution of some baseline characteristics depending on the molecular profile is shown in Table 1. Figure 1
Conclusion:
This trial will provide robust evidence if a tailored therapeutic strategy based on selected gene expression profile may contribute to improve efficacy and to ameliorate toxicity of adjuvant chemotherapy in completely resected early stage NSCLC.
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ORAL04.04 - Discussant for ORAL04.01, ORAL04.02, ORAL04.03 (ID 3559)
11:18 - 11:28 | Author(s): H. Borghaei
- Abstract
- Presentation
Abstract not provided
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ORAL04.05 - Results Ph III Trial Customized Adjuvant CT after Resection of NSCLC with Lymph Node Metastases SCAT: A Spanish Lung Cancer Group Trial (ID 2983)
11:28 - 11:39 | Author(s): B. Massuti, J.M. Rodriguez-Paniagua, M. Cobo Dols, R. Arrabal, I. Ballesteros, Y.W. Pun, T. Moran, P. Lopez De Castro, J.L. González-Larriba, F. Hernando Trancho, J. De Castro, P. Diaz-Agüero, I. Barneto, C. Baamonde, S. Ponce, J.L. Martin De Nicolas, M.A. Muñoz, J.C. Peñalver, M.D. Isla, J.J. Rivas De Andres, G. Lopez-Vivanco, J. Pac, J.M. Sanchez, J. Sanchez-Paya, R. Rosell
- Abstract
- Presentation
Background:
Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement (St II-IIIA) but compliance and outcomes remain limited. Analysis of expression of genes involved in DNA repair could be used to individualize optimal CT. BRCA1 is primarily involved in the repair of double strand DNA breaks and functions as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. BRCA1 defficiency can enhance Cis resistance. Loss of BRCA1 function is associated to sensitivity to DNA-damaging CT and may also be associated with resistance to spindle poisons
Methods:
Randomized phase III multicenter trial. After surgery patients (p) with St II and III NCSLC were random 1:3 to control arm (3 cycles Cis-Docetaxel) or to experimental arm with treatment assigned according BRCA1 expression levels (low levels: Cis-Gemcitabine; intermediate levels: Cis-Doc; high levels: Docetaxel alone). Stratifification factors: N1 vs N2; age < or > 65 y; non-Squamous vs Squamous (Sq) histology; lobectomy vs pneumonectomy). Planned PORT in N2. Primary end-point OS. Secondary end-points DFS, toxicity profile (CTCAE v 3.0) /compliance, recurrence pattern. Statistical hypothesis: increase 20% 5y survival rate control group (45%)
Results:
From June/2007 to May/2013, a total of 591 p were screened and 500 of them were randomized in the study, 108 in control arm, 392 in experimental arm. In experimental arm 110 p received Cis-Gem, 127 Cis-Doc and 110 Doc alone. There were no significant differences between arm for known prognostic factors: Median age 64 y; 79% males, 21% females; 43% Sq, 49% Adenoca, 8% others; 57% former smokers, 32% current smokers, 11% never smokers; pneumonectomy 26%; N1 58%, N2 48%. Median tumor size 4.4 cm (0.8-15.5 cm). Median mRNA BRCA1 levels 15.78 (0.73-132). Mean BRCA1 levels 6.95 in Adenoca vs 20.29 in Sq (p<0.001). P with Sq histology showed a longer DFS (HR 0.73; p=0.05) but without differences in OR (HR 1) Median follow-up 28 months (0-79 m), with a cut-off of March 15[th] 2015, median survival has not reached both arms and no significant differences have been seen for OS with hazard ratio (HR) 0.866 (p=0.45) or DFS with HR 1. In experimental group HR for OS was 0.842 (NS) comparing low with high-BRCA1 levels. In p with high-BRCA1 levels control treatment (Cis-Doc) was superior to experimental (Doc) with HR 1.24 (NS).In non-Sq histology experimental treatment was superior to control with HR 0.75. For p receiving all planned treatment HR is 0.63 with p = 0.043 compared with p not able to complete treatment.
Conclusion:
Overall survival data are still immature because median survival is not reached with a median f-u 28 m for this N+ population. At this time analysis BRCA1 based adjuvant CT does not improve overall OS. In p with high BRCA1 levels Doc alone is inferior to Cis-Doc. BRCA-1 levels are higher in Sq and in non-Sq histology a trend to better survival in experimental arm was found. Full dose of planned treatment confers a survival advantage, however, longer follow-up is still warranted.
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ORAL04.06 - Impact of Demographic and Health System Factors on Adjuvant Chemotherapy Use in Stage II Non-Small Cell Lung Carcinoma: A National Cancer Database Analysis from 2000 to 2012 (ID 3056)
11:39 - 11:50 | Author(s): G. Goyal, P.T. Silberstein
- Abstract
- Presentation
Background:
Non-small cell carcinoma is the most common type of lung cancer. A few recent prospective trials have shown that the addition of adjuvant chemotherapy after operable stage II non-small cell carcinoma patients is associated with an improved survival[1,2]. Adjuvant chemotherapy is effective but underutilized. Our aim was to analyze the practice patterns for adjuvant chemotherapy use in stage II non-small cell lung carcinoma using the National Cancer Database (NCDB).
Methods:
We selected a historical cohort of patients diagnosed with stage II non-small cell carcinoma between 2000 and 2012. This cohort is selected from the National Cancer Database (NCDB). NCDB is a national oncology outcomes database that includes 70% of new cancer diagnoses from more than 1,500 Commission on Cancer accredited programs in the United States and Puerto Rico. We studied this cohort to find out the difference in patterns of adjuvant chemotherapy use among stage II non-small cell carcinoma patients based on demographic and insurance characteristics. Two-tailed chi-square test was used as the test of significance with a p-value < 0.05 being considered significant. All values are given in percentages.
Results:
The total number of patients diagnosed with stage II lung cancer between the years 2000 to 2012 was analyzed (n=112430). We observed an increase in the percentage of patients receiving adjuvant chemotherapy from 9% to 18% from the year 2003 to 2004. The factors associated with increased adjuvant chemotherapy use were private insurance, ages 30 to 69, White/Hispanic race, higher education, higher income groups and female gender (p<0.0001)(Table 1). Table 1. Adjuvant Chemotherapy use in stage II Non-Small cell lung cancer.VARIABLES INCLUDED PERCENTAGE OF PATIENTS RECEIVING ADJUVANT CHEMOTHERAPY Diagnosis year 2000-2003 6 2003-2012 23 Age <30 7 30-49 22 50-69 25 69-89 9 Insurance status Private/managed 26 Medicaid 19 Medicare 15 Uninsured 17 Sex Male 17 Female 19 Annual Household Income (USD: 2012 census) <36000 15 36000-43999 17 44000-52999 18 53000-68999 19 >69000 21 Educational Status (% Patients without HS degree) >23% 15 15-22.9% 17 11- 14.9% 18 6-10.9% 19 <6% 21 Race White 18 Black 17 Hispanic 19 Charlson comorbidity score None 21 One 23 >= 2 18
Conclusion:
This cohort illustrates the increase in adjuvant chemotherapy use from 2000 to 2012 with significant increase during the year of 2004. Access to adjuvant chemotherapy is dependent on various demographic factors. The treatment and outcomes of non-small cell carcinoma is dependent on the type of treatment used, which itself is affected by the population demographics and health system factors. These variables should be studied in detail to find out the cause for the underutilization of adjuvant chemotherapy despite the evidence of survival benefit in patients with stage II non-small cell carcinoma of lung.
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ORAL04.07 - Adjuvant Chemotherapy in Patients with Resected Non-Small-Cell-Lung Cancer Treated with Carboplatin and Oral Vinorelbine - SWITCH I Study (ID 497)
11:50 - 12:01 | Author(s): V. Kolek, I. Grygarkova, L. Koubkova, J. Skrickova, L. Ostrizkova, J. Svecova, D. Sixtova
- Abstract
- Presentation
Background:
Adjuvant cisplatinum-based chemotherapy is recommended in patients with stages IB (≥ 4 cm), IIA, IIB, and IIIA of non small-cell lung cancer (NSCLC) after radical resection. Vinorelbine with cisplatin are preferable drugs in this indication, but the side effects of this treatment were not negligible in big adjuvant trials. Carboplatin with vinorelbine given intravenously switched to orally were applied in a multicentre prospective study SWITCH I to give better comfort, higher tolerability and comparable effectivenes as standard adjuvant chemotherapy. The recruitment period started in January 12[th], 2005 and lasted till September 5[th], 2008.
Methods:
Consecutive chemo-naive patients were recruited after complete resection of NSCLC stages IB, IIA, IIB and IIIA. Chemotherapy was applied from 2 to 6 weeks after complete resection. Four cycles of 21 days regimens were planned, Patients received carboplatin AUC 5 on the day 1,vinorelbine 25 mg/m[2] intravenously on the day 1 switched to 60 mg/m[2] orally on the day 8. Follow-up visits with physical evaluation, chest CT and laboratory tests have been realized every 3 months for 2 years and then every 6 months. Tolerability, side effects, relative dose intensity and survival were evaluated.
Results:
Seventy four patients (pts) were recruited to the SWITCH I study: 53 men and 21 women, 45 smokers, 23 ex- smokers and 6 non-smokers. Median age was 64 y (48-75 y). Tumor was squamous in 46, adenocarcinoma in 22, giant cell in 4 and NOS in 2 pts. Stage of the tumor was IB in19, IIA in 8, IIB in 22 and IIIA in 25. Mean number of applied cycles was 3.77 four planned cycles finished 82,4% patients. The most frequent hematological toxicities grade 3/4 were neutropenia (25.7 %), leukopenia (16.2 %), anemia (8.1 %) and trombocytopenia (2.7 %). Non-hematological toxicities were alopecia (12.2 %), nausea (4.1%), nefrotoxicity (1.4%) and diarrhoea (1,4%). Median of follow up was 4.73 y. Median of disease specific survival was 7.63 y (95% CI: 4.57 to NR), median of overall survival (MOS) was 5.9 y (95% CI, 3.7 to, NR) and median of disease free survival (DFS) 4.43 y . Three-year survival of 70.3% and five-year survival of 56,2% were reached.
Conclusion:
Adjuvant chemotherapy with carboplatinum and vinorelbine given intravenously on the day 1 and orally on the day 8 in 21 day regimen appears to be a comfortable and tolerable therapy in radically resected NSCLC. It provides higher dose intensity and more of acomplished treatments compared to big adjuvant trials and LACE meta-analysis, in which these parametres varied between 50 % to 76 % only. Survival results are comparable to LACE (3-year survival 70,3% vs 64.3%), 5-year survival 56,2% vs 55.1%) and MOS 5.9 vs 5.15 y). Supported by Grant Grant IGA MZ ČR NT/13569 of the Czech Ministry of Health.
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ORAL04.08 - Discussant for ORAL04.05, ORAL04.06, ORAL04.07 (ID 3468)
12:01 - 12:11 | Author(s): G.V.V. Scagliotti
- Abstract
- Presentation
Abstract not provided
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GR 01 - Management of Challenging Clinical Scenarios in Localized Lung Cancer (ID 14)
- Event: WCLC 2015
- Type: Grand Rounds
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:G. Darling, J. Mitchell
- Coordinates: 9/08/2015, 14:15 - 15:45, 601+603
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GR01.04 - Salvage Surgery After Definitive Chemoradiation Therapy (CRT) (ID 1831)
15:20 - 15:40 | Author(s): E. Vallieres
- Abstract
- Presentation
Abstract:
After definitive CRT, approximately 25-30% of patients with stage III disease will fail at their primary site while the regional and systemic fields are under control. As a result, the question of whether some of these patients may potentially benefit from salvage resection of their primary site is often brought up at multidisciplinary tumor boards. The largest published series is from Duke who reported earlier this year on 31 patients in 17 years who underwent lobectomy after definitive radiation therapy (RT), 29 of whom had also received concurrent chemotherapy. Median dose of RT was 60Gy, ranging from 40 to more than 70. The median interval in between completion of the RT and the lobectomy was 18 weeks, ranging from 8 to 111. The majority of these resections were done open though, to their credit, 6 were done VATS without conversion. There was no operative mortality and 48% patients experienced some complications, only a third of these being major. There were no post op bronchopleural fistulae (BPF) despite only a third of patients having their stumps covered: 30/31 achieved an R0 resection, 19/31 had viable tumor in the specimen as histological confirmation of recurrence / persistent disease was not mandated before resection. Median follow-up (f-up) was 26 months and the median OS was 60 months: 20 months if persistent tumor was present in the resected specimen. For the patients who went to salvage resection for recurrent disease (n=3: DFIs being 240, 300 and 700 days) the OS was 9 months, significantly less than the 26 months of those who had persistent disease after RT. The 5 y survival was 31%, 0 if N1-2 disease was present at resection or if salvage was done for relapse, but very small numbers… (1) In 2013, the Yale group reported on 14 patients in 6 years who underwent salvage resection for biopsy proven persistent/ recurrent T disease after definitive CRT. Most underwent lobectomies (9), 2 pneumonectomies. 36% underwent stump coverage. There was no mortality at 90 days, 43% experienced some complication, including 1 ARDS and I BPF. Median post op survival was 9 months, mean 2 year survival was 49%.(2) Bauman in 2008 reported on 24 patients in 8 years who underwent salvage resection after RT, mean dose of 64 Gy (59 to 70), 22 had received concurrent chemo. The interval from completion of RT to surgery ranged from 5 to 94 weeks (median 21). Most underwent lobectomies but 10 were pneumonectomies, including 4 right sided. 19/24 had stump coverage, 16 by omentopexy. Median OR time was 5.5 hours. There was one post op death due to ARDS, 58% experienced some complications, no BPF. 80% of specimen had viable tumor, 2 had R1 resections, 11/24 had N1-2. Median f-up was 29 months, median OS was 30 months, 43 months if PET information/changes led to salvage resection. The estimated 3 year survival was 47%: 2 patients had were found to have brain metastases within 2 months of the salvage resection, neither had had brain imaging in the re-evaluation leading to salvage surgery.(3) Personal opinion (4): the preoperative evaluation of such candidates should always include fresh CT PET, brain MRI and PFTs including a DCO as well as a quantitative perfusion scan as the possibilities of pneumonectomy are not insignificant in this population. Smoking cessation is mandatory. The location of the tumor at presentation also matters: it may be technically much more difficult to perform a lobectomy for centrally radiated lesions. Though not the topic at hand, in my experience, the technical challenges to salvage after SABR pale in comparison as usually the hilar structures are relatively intact after SABR. These surgeries can be challenging and I would encourage that one obtain as much information as possible upfront before going to resection. This includes that one attempt to obtain histological confirmation of viable cancer before undertaking these surgeries. We now know that after RT, particularly after SABR, the PET information may be falsely positive. Along the same lines, I will get EBUS sampling of the mediastinal and hilar lymph nodes before resection. If negative, I will add mediastinoscopy evaluation even in those who had mediastinoscopy at presentation. (5) Intraoperatively, you need to communicate with anesthesia that these patients do not tolerate excess IV fluid well at all as a result of having had their mediastinum radiated. We prepare/ harvest the intercostal muscle bundle at entry. Early circumferential control of the proximal PA and PVs early on is also favored… just in case. Intrapericardial access to the PVs often helps when the hilum is fibrosed, in such instances, open division of the lobar bronchus will often help accessing the lobar PA branches, particularly with the RUL. We cover all of our stumps with the prepared intercostal bundle. Post-operatively, IV fluid restriction remains a priority. Patients whose left hilar dissection was difficult are kept fasting until the left recurrent nerve function is evaluated or judged to be intact. Any concern prompts immediate laryngoscopic evaluation and temporary medialization of any suspicious “lazy” vocal cord follows. The literature on the topic is sparse and all retrospective but we can conclude from its review that: in experienced hands, such resections can be performed safely with acceptable morbidity, such resections, particularly if one is attempting to perform less than a pneumonectomy can be technically challenging and that selection of the patients who may benefit the most from such surgery is not easy. References: Yang CJ, Meyerhoff RR, Stephens SJ, et al. Long-Term Outcomes of Lobectomy for Non-Small Cell Lung Cancer After Definitive Radiation Treatment. Ann Thorac Surg 2015; 99:1914–20 Kuzmik GA, Detterbeck FC, Decker RH, et al. Pulmonary resections following prior definitive chemoradiation therapy are associated with acceptable survival Eur J Card-Thorac Surg 44 (2013) e66–e70 Bauman JE, Mulligan MS, Martins RG, et al. Salvage Lung Resection After Definitive Radiation (>59 Gy) for Non-Small Cell Lung Cancer: Surgicaland Oncologic OutcomesAnn Thorac Surg 2008;86:1632–9 Page B, Blitz M, Louie BE, et al. Pulmonary Resection of NSCLC can be performed safely following definitive chemoradiotherapy. Oral presentation 13th World Conference on Lung Cancer, San Francisco, CA August 1[st] 2009, J Thorac Oncol. 4(9) Supplement 1:S301, September 2009 Louie BE, Kapur S, Farivar AS, et al. Safety and Utility of Mediastinoscopy in Non-Small Cell Lung Cancer in a Complex Mediastinum, Ann Thorac Surgery 92(1): 278-83, 2011
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ORAL 34 - Quality/Survival/Prognosis in Localized Lung Cancer (ID 153)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:B.C. Cho, R.L. Keith
- Coordinates: 9/09/2015, 16:45 - 18:15, 201+203
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ORAL34.03 - Prognostic Factors in Early Stage NSCLC: Analysis of the Placebo Group in the MAGRIT Study (ID 24)
17:07 - 17:18 | Author(s): E. Vallieres
- Abstract
- Presentation
Background:
The MAGRIT study was a worldwide, multicenter, phase-3 double-blind, randomized trial evaluating efficacy of the MAGE-A3 Cancer Immunotherapeutic in resected non-small cell lung cancer (NSCLC) (www.clinicaltrials.gov NCT00480025). We examined baseline patient and disease characteristics associated with overall survival (OS) and disease-free survival (DFS) among patients assigned to placebo.
Methods:
Study participants were ≥18 years, with histologically proven, MAGE-A3-positive stage IB, II or IIIA NSCLC (AJCC 6.0). Participants had undergone complete anatomical resection of the tumor (lobectomy or pneumectomy) with mediastinal lymph node (LN) dissection or sampling according to standard of care. Up to four cycles of platinum-based adjuvant chemotherapy were allowed. Cox regression models were used to explore characteristics that could predict DFS and OS. Factors statistically significant in univariate analysis (p<0.05) were included in multivariate models using a stepwise approach (p<0.05 to enter/remain in the model).
Results:
There were 757 placebo patients in the total treated population; median age 63 years, 76% male, 53% with squamous cell carcinoma (SCC), 34% with adenocarcinoma, 98% with performance status 0-1, 52% had received adjuvant chemotherapy.In univariate analyses, SCC, lower N-category and earlier disease stage were associated with improved DFS. Lower N-category, earlier stage and smaller tumor size were associated with improved OS. In multivariate analysis, N-category (HR 1.34, 95%CI [1.16-1.55]) and histological type (HR for SCC vs non-SCC 0.64, 95%CI [0.51-0.81]) remained significant for DFS. N-category (HR 1.47, 95%CI [1.21-1.79]) and tumor size (HR by unit increase 1.08, 95%CI [1.01-1.15]) did so for OS. No association was found between DFS or OS and age, gender, race, region, baseline performance status, quantitative MAGE-A3 expression, chemotherapy administration or type of chemotherapy, smoking status or type of LN sampling (minimal/systematic). Among patients with SCC, univariate analysis identified increased number of chemotherapy cycles and operative technique (pneumectomy) as associated with improved DFS (p<0.05). Only operative technique remained in the multivariate model. When including N-category (p<0.10 in univariate analysis) in the multivariate model, N-category and number of chemotherapy cycles were also selected. Lower N-category and smaller tumor size were significantly associated with improved OS, in univariate and multivariate analyses. Among patients with non-SCC, univariate analysis identified younger age, being female, lower N-category and earlier disease stage with improved DFS, and lower N-category, earlier disease stage and region (East Asia) with improved OS. N-category and gender, and N-category and region remained significant in the multivariate analysis for DFS and OS, respectively.
Conclusion:
This is the first prognostic factor analysis in resected NSCLC performed on data from a large, prospective randomized study. It highlighted that in terms of DFS, SCC patients have a better prognosis than non-SCC patients. N-category plays a major role in determining prognosis. Operative technique (pneumectomy), number of chemotherapy cycles (SCC) and gender (non-SCC) are also associated with outcome. Variables predictive for OS are N-category and tumor size (all) and region (non-SCC). These results confirm retrospective studies done within the context of TNM classification, but add that histopathology subtype is a strong determinant for DFS in resected NSCLC.
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ORAL 35 - Surgical Approaches in Localized Lung Cancer (ID 155)
- Event: WCLC 2015
- Type: Oral Session
- Track: Treatment of Localized Disease - NSCLC
- Presentations: 1
- Moderators:M. de Perrot, J. Mitchell
- Coordinates: 9/09/2015, 16:45 - 18:15, 601+603
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ORAL35.01 - Surgical Approach and Disease Recurrence in NSCLC Patients in the MAGRIT Study (ID 318)
16:45 - 16:56 | Author(s): E. Vallieres
- Abstract
- Presentation
Background:
Surgical resection is the standard treatment for early stage Non-Small Cell Lung Cancer (NSCLC). Anatomical resection with lymphadenectomy is recommended in surgically treated patients with Stage I-IIIA NSCLC. Whether mediastinal lymph node dissection (MLND) or mediastinal lymph node sampling (MLNS) should be performed remains controversial, and there is currently no consensus within the literature. We describe surgical approaches and patterns of disease recurrence in patients enrolled in MAGRIT: a large global randomized study of the MAGE-A3 Cancer Immunotherapeutic versus placebo after complete tumor resection (Phase III trial, MAGRIT, NCT00480025).
Methods:
Study participants were aged ≥18 years, with histologically-proven, MAGE-A3-positive Stage IB, II or IIIA NSCLC (AJCC 6.0) who had undergone R0 anatomic resection of their tumor (lobectomy or pneumonectomy) with mediastinal lymphadenectomy. Patients were randomized to MAGE-A3 or placebo in a 2:1 ratio. A total of 2,272 patients were treated at 556 centers in 34 countries. Because MAGRIT did not demonstrate efficacy overall, and because the number of recurrences in the placebo arm was small (n=271), recurrence patterns by surgical technique are presented in the overall population. An analysis of the placebo population was also conducted as the overall population results are subject to potential bias (a limited treatment effect in small sub-groups cannot be excluded). Cox regression models were used to explore whether lymphadenectomy procedure could be prognostic for disease-free survival (DFS) or overall survival (OS).
Results:
In the total treated population, 76% were men, 52% had squamous cell carcinoma, and 52% received adjuvant chemotherapy. More than half (57%) of patients were enrolled in Europe, with 23% in East Asia, 16% in North America and 4% in other countries. 47% of patients had Stage IB, 6.5% IIA, 30% IIB, and 17% IIIA disease. Lobectomy (including bi- and sleeve-lobectomy) was performed in 85% of patients, and 14% required pneumonectomy. MLNS was performed in 53% and MLND in 47% of patients. MLNS and MLND patients had a similar disease stage distribution. By region, the percentage of patients who underwent MLNS was: 36% in Europe, 65% in East Asia, 94% in North America and 59% in other countries. Among patients who had undergone MLNS or MLND, 37% (n=447/1202) and 36% (379/1067) developed recurrent disease, respectively. Loco-regional recurrence was observed in 40% (177/447) of patients after MLNS and 31% (118/379) after MLND, with distant recurrence observed in 55% (244/447) and 64% (244/379), respectively. There was no difference in the pattern of distant metastases between patients who had MLNS or MLND. Cox modeling showed no impact of the extent of lymphadenectomy on either DFS or OS. A separate analysis of patients in the placebo arm demonstrated similar trends to those of the total study population.
Conclusion:
Lobectomy (including bi- and sleeve-lobectomy) was the most frequently used treatment for patients who participated in the MAGRIT study. Important regional differences in lymphadenectomy were observed. Although the patterns of recurrence varied to some extent with the type of lymphadenectomy, our study did not demonstrate any prognostic impact related to the type of lymphadenectomy performed.
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