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PL 02.06 The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for R Status Descriptors for Non-Small Cell Lung Cancer
November 2017
Abstracts
S1605
PL 02.04 SCAT Ph III Trial: Adjuvant CT Based on BRCA1 Levels in NSCLC N+ Resected Patients. Final Survival Results a Spanish Lung Cancer Group Trial
PL 02.06 The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for R Status Descriptors for Non-Small Cell Lung Cancer
B. Massuti,1 M. Cobo,2 M. Rodriguez-Paniagua,1 I. Ballesteros,3 T. Moran,4 R. Arrabal,2 J.L. Gonzalez Larriba,5 I. Barneto,6 Y. Wah Pun,3 J. de Castro Carpeño,7 S. Ponce-Aix,8 C. Baamonde,6 M.A. Muñoz,9 G. Lopez-Vivanco,10 J.J. Rivas de Andres,11 D. Isla,12 R. Lopez,13 J.M. Sanchez,14 J. Sánchez-Payá,1 R. Rosell15 1Alicante University Hospital, Alicante/ES, 2Hospital Carlos Haya, Malaga/ES, 3 Hospital La Princesa, Madrid/ES, 4Catalan Institute of Oncology, Badalona/ES, 5Hospital Clínico San Carlos, Madrid/ES, 6Hospital Reina Sofia, Cordoba/ES, 7Hospital Universitario La Paz, Madrid/ES, 8 Hospital 12 de Octubre, Madrid/ES, 9Instituto Valenciano Oncología, Valencia/ES, 10Hospital de Cruces de Barakaldo, Vizcaya/ES, 11 Hospital Miguel Servet, Zaragoza/ES, 12Hospital Lozano Blesa, Zaragoza/ES, 13Hospital Clinico Universitario de Santiago de Compostela, Santiago De Compostela/SPAIN, 14MD Anderson Cancer Center, Madrid/ES, Grupo Español de Cancer de Pulmon (GECP), Barcelona/ES, 15Grupo Español de Cancer de Pulmon (GECP), Barcelona/ES
J. Edwards,1 K. Chansky,2 L. Shemanski,2 P. Van Schil,3 H. Asamura,4 R. Rami-Porta5 1Department of Cardiothoracic Surgery, University of Sheffield, Sheffield/GB, 2Biostatistics, Cancer Research and Biostatistics, Seattle, WA/US, 3Department of Thoracic and Vascular Surgery, Antwerp University Hospital and University of Antwerp, Edegem/BE, 4Division of Thoracic Surgery, Keio University School of Medicine, Tokyo/JP, 5Thoracic Surgery, Hospital Universitari Mutua Terrassa, and Ciberes Lung Cancer Group, Terrassa/ES
Background: Postop platinum-based CT is considered standard of care in resected NSCLC with lymph node involvement. BRCA1 and BRCA2 are important DNA repair factors primarily involved in the repair of double strand DNA breaks. BRCA-1 functions may act as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. BRCA1 defficiency enhances Cis resistance and loss of BRCA1 function is associated to sensitivity to DNA-damaging CT and may also be associated with resistance to spindle poisons. Methods: SCAT randomized phase III multicenter trial tests individualized optimal CT based on expression of BRCA1. 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). Stratification 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: 5y survival rate control group (45%) could be increase 20% in experimental arm. 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). Compliance of CT was better in experimental arm with less dose-reductions and without differences according extent of surgery. CT compliance was lower in patients older 70 y. Median PFS: 38.7 m (control), 32.2 m Cis-Gem, 34.3 m Cis-Doc and 41 m Doc. At 5 years, event-free rate is 54% in control arm and 56% in experimental arm and median OS 73.3 m (control) vs 77.5 m (exp) (p¼0.75). In experimental arm: Docetaxel alone 80.2 m, Cis-Doc 80.5 m and Cis-Gem 74 m. Conclusions: Higher survival than expected in patients with lymph node involvement. No significant difference in survival achieved with the experimental arm. In case of high levels BRCA CT treatment without cisplatin is not detrimental.
Background: The residual tumor (R) classification describes the tumor status after treatment. It reflects the effectiveness of treatment has prognostic impact and may affect further treatment. We analyzed existing and potential R status criteria, including the proposed IASLC definition for “uncertain” resection margin status (2005), from data collected for the IASLC Lung Cancer Staging Project. Method: This analysis is based on 14,712 patients undergoing NCSLC surgery, for whom full R status and survival data were available. R status criteria and the following data were evaluated: number of N2 stations explored; lobe-specific systematic lymph node dissection (SLND); extra-capsular extension (ECE); status of the highest station; bronchial carcinoma in situ (cis) at bronchial resection margin (BRM); pleural lavage cytology (PLC). Revised categories of R0, R(un), R1 and R2 were designated and tested for survival impact. Result: There were 14,293 R0, 263 R1 and 156 R2 cases, with median survival not reached, 33 and 29 months (p<0.0001). R status correlated with T and N stages (p<0.0001). Greater or equal to 3 N2 stations were explored for 9,290 cases (63%) and lobe-specific SLND in 6,619 (45%), with positive associations for increasing pN2 stage (p<0.0001). ECE was recorded in 61 (20%) of 304 N+ cases evaluated. The highest station was positive in 942 (6.4%) cases. PLC was positive in 59 (3.6%) of 1,646 cases and there was BRM cis in 13 cases. After reassignment according to the IASLC proposed definition, there were 6,103 R0 cases, 8,203 R(un), 250 R1 and 156 R2. Conclusion: These data confirm the proposed criteria for Uncertain R status, R(un), with a prognosis stratifying between R0 and R1. Further detailed prospective data collection is required to characterize fully the prognostic impact of these criteria. Detailed evaluation of R status is of particular importance in the design and analyses of clinical trials of adjuvant therapies. Keywords: Resection margin, Staging, Prognosis
Abstracts
S1605
PL 02.04 SCAT Ph III Trial: Adjuvant CT Based on BRCA1 Levels in NSCLC N+ Resected Patients. Final Survival Results a Spanish Lung Cancer Group Trial
PL 02.06 The IASLC Lung Cancer Staging Project: Analysis of Resection Margin Status and Proposals for R Status Descriptors for Non-Small Cell Lung Cancer
B. Massuti,1 M. Cobo,2 M. Rodriguez-Paniagua,1 I. Ballesteros,3 T. Moran,4 R. Arrabal,2 J.L. Gonzalez Larriba,5 I. Barneto,6 Y. Wah Pun,3 J. de Castro Carpeño,7 S. Ponce-Aix,8 C. Baamonde,6 M.A. Muñoz,9 G. Lopez-Vivanco,10 J.J. Rivas de Andres,11 D. Isla,12 R. Lopez,13 J.M. Sanchez,14 J. Sánchez-Payá,1 R. Rosell15 1Alicante University Hospital, Alicante/ES, 2Hospital Carlos Haya, Malaga/ES, 3 Hospital La Princesa, Madrid/ES, 4Catalan Institute of Oncology, Badalona/ES, 5Hospital Clínico San Carlos, Madrid/ES, 6Hospital Reina Sofia, Cordoba/ES, 7Hospital Universitario La Paz, Madrid/ES, 8 Hospital 12 de Octubre, Madrid/ES, 9Instituto Valenciano Oncología, Valencia/ES, 10Hospital de Cruces de Barakaldo, Vizcaya/ES, 11 Hospital Miguel Servet, Zaragoza/ES, 12Hospital Lozano Blesa, Zaragoza/ES, 13Hospital Clinico Universitario de Santiago de Compostela, Santiago De Compostela/SPAIN, 14MD Anderson Cancer Center, Madrid/ES, Grupo Español de Cancer de Pulmon (GECP), Barcelona/ES, 15Grupo Español de Cancer de Pulmon (GECP), Barcelona/ES
J. Edwards,1 K. Chansky,2 L. Shemanski,2 P. Van Schil,3 H. Asamura,4 R. Rami-Porta5 1Department of Cardiothoracic Surgery, University of Sheffield, Sheffield/GB, 2Biostatistics, Cancer Research and Biostatistics, Seattle, WA/US, 3Department of Thoracic and Vascular Surgery, Antwerp University Hospital and University of Antwerp, Edegem/BE, 4Division of Thoracic Surgery, Keio University School of Medicine, Tokyo/JP, 5Thoracic Surgery, Hospital Universitari Mutua Terrassa, and Ciberes Lung Cancer Group, Terrassa/ES
Background: Postop platinum-based CT is considered standard of care in resected NSCLC with lymph node involvement. BRCA1 and BRCA2 are important DNA repair factors primarily involved in the repair of double strand DNA breaks. BRCA-1 functions may act as a differential regulator of response to cisplatin (Cis) and antimicrotubule agents. BRCA1 defficiency enhances Cis resistance and loss of BRCA1 function is associated to sensitivity to DNA-damaging CT and may also be associated with resistance to spindle poisons. Methods: SCAT randomized phase III multicenter trial tests individualized optimal CT based on expression of BRCA1. 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). Stratification 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: 5y survival rate control group (45%) could be increase 20% in experimental arm. 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). Compliance of CT was better in experimental arm with less dose-reductions and without differences according extent of surgery. CT compliance was lower in patients older 70 y. Median PFS: 38.7 m (control), 32.2 m Cis-Gem, 34.3 m Cis-Doc and 41 m Doc. At 5 years, event-free rate is 54% in control arm and 56% in experimental arm and median OS 73.3 m (control) vs 77.5 m (exp) (p¼0.75). In experimental arm: Docetaxel alone 80.2 m, Cis-Doc 80.5 m and Cis-Gem 74 m. Conclusions: Higher survival than expected in patients with lymph node involvement. No significant difference in survival achieved with the experimental arm. In case of high levels BRCA CT treatment without cisplatin is not detrimental.
Background: The residual tumor (R) classification describes the tumor status after treatment. It reflects the effectiveness of treatment has prognostic impact and may affect further treatment. We analyzed existing and potential R status criteria, including the proposed IASLC definition for “uncertain” resection margin status (2005), from data collected for the IASLC Lung Cancer Staging Project. Method: This analysis is based on 14,712 patients undergoing NCSLC surgery, for whom full R status and survival data were available. R status criteria and the following data were evaluated: number of N2 stations explored; lobe-specific systematic lymph node dissection (SLND); extra-capsular extension (ECE); status of the highest station; bronchial carcinoma in situ (cis) at bronchial resection margin (BRM); pleural lavage cytology (PLC). Revised categories of R0, R(un), R1 and R2 were designated and tested for survival impact. Result: There were 14,293 R0, 263 R1 and 156 R2 cases, with median survival not reached, 33 and 29 months (p<0.0001). R status correlated with T and N stages (p<0.0001). Greater or equal to 3 N2 stations were explored for 9,290 cases (63%) and lobe-specific SLND in 6,619 (45%), with positive associations for increasing pN2 stage (p<0.0001). ECE was recorded in 61 (20%) of 304 N+ cases evaluated. The highest station was positive in 942 (6.4%) cases. PLC was positive in 59 (3.6%) of 1,646 cases and there was BRM cis in 13 cases. After reassignment according to the IASLC proposed definition, there were 6,103 R0 cases, 8,203 R(un), 250 R1 and 156 R2. Conclusion: These data confirm the proposed criteria for Uncertain R status, R(un), with a prognosis stratifying between R0 and R1. Further detailed prospective data collection is required to characterize fully the prognostic impact of these criteria. Detailed evaluation of R status is of particular importance in the design and analyses of clinical trials of adjuvant therapies. Keywords: Resection margin, Staging, Prognosis