International Journal of
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation
Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival John M. Varlotto, MD,* Aaron N. Yao, PhD,y Malcolm M. DeCamp, MD,z,x Satvik Ramakrishna, MD,x Abe Recht, MD,jj John Flickinger, MD,{ Adin Andrei, PhD,# Michael F. Reed, MD,**,yy Jennifer W. Toth, MD,**,zz Thomas J. Fizgerald, MD,* Kristin Higgins, MD,xx Xiao Zheng, PhD,y Julie Shelkey, MD,jjjj Laura N. Medford-Davis, MD,{{ Chandra Belani, MD,## and Christopher R. Kelsey, MD*** *Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts; yDepartment of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia; zDivision of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois; xNorthwestern University School of Medicine, Chicago, Illinois; jjDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; {Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; #Northwestern University, Chicago, Illinois; **Pennsylvania State University College of Medicine, Hershey, Pennsylvania; yyHeart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania; zzDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania; xxDepartment of Radiation Oncology, Emory University, Atlanta, Georgia; jjjjDepartment of Anesthesiology, Columbia University, New York, New York; {{ Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas; ##Pennsylvania State University-Hershey Cancer Institute, Hershey, Pennsylvania; and ***Department of Radiation Oncology, Duke University Cancer Institute, Durham, North Carolina Received Jul 28, 2014, and in revised form Dec 8, 2014. Accepted for publication Dec 11, 2014.
Summary Nodal stage of surgically resected non-small cell lung cancer is related to distal recurrence and overall survival, but not local recurrence.
Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202,
Reprint requests to: John M. Varlotto, MD, University of Massachusetts, Health Alliance Medical Center, 275 Nichols St, Fitchburg, MA 01420. E-mail: [email protected] Int J Radiation Oncol Biol Phys, Vol. 91, No. 4, pp. 765e773, 2015 0360-3016/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.12.028
Dr Yao was supported by National Cancer Institute grant 2R25CA093423. Conflict of interest: none.
766
International Journal of Radiation Oncology Biology Physics
Varlotto et al.
and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] Z 1.84, 95% confidence interval [CI]: 1.30-2.59; PZ.001; N2, HR Z 2.32, 95% CI: 1.55-3.48; P70 Predicted 70 Predicted Unknown Type of surgery Pneumonectomy Segmentectomy Wedge Bilobectomy Tumor size Mean (SD) >3 cm 3 cm Unknown No. of hilar/intralobar LNs removed (range) No. of hilar/intralobar LNs involved (range) No. of med LNs removed (range) No. of med LNs involved (range) Adjuvant chemotherapy Yes No Histology Adenocarcinoma Adenosquamous Bronchoalveolar carcinoma Large-cell cancer NSCLC-NOS Squamous cell Unknown Grade 1
67.1 (9.7)
67.5 (9.7)
65.8 (9.2)
65 (9.9)
848 (54.1) 720 (45.9)
648 (52.2) 593 (47.8)
132 (65.4) 70 (34.7)
68 (54.4) 57 (45.6)
200 (12.8) 1362 (86.9) 6 (0.4)
154 (12.4) 1084 (87.4) 3 (0.2)
28 (13.9) 173 (85.6) 1 (0.5)
18 (14.4) 105 (84) 2 (1.6)
P value .003 .002
.18
.012 210 442 244 71 574 27
(13.4) (28.2) (15.6) (4.5) (36.6) (1.7)
167 351 189 59 465 10
(13.5) (28.3) (15.2) (4.8) (37.5) (0.8)
25 59 36 7 69 6
(12.4) (29.2) (17.8) (3.5) (34.2) (3)
18 36 19 5 40 7
(14.4) (28.8) (15.2) (4) (32) (5.6)
67.9 181 328 1059
(20.3) (11.5) (20.9) (67.5)
66.8 104 199 938
(21.6) (8.4) (16) (75.6)
69 42 70 90
(18.6) (20.8) (34.7) (44.6)
70.3 35 59 31
(17.9) (28) (47.2) (24.8)
2 209 259 1100
(0.7) (13.3) (16.5) (70.2)
1.9 110 163 968
(0.8) (8.9) (13.1) (78)
2.1 50 58 94
(0.7) (24.8) (28.7) (46.5)
2.2 49 38 38
(0.7) (39.2) (30.4) (30.4)
78.5 251 166 1151
(23.2) (16) (10.6) (73.4)
76.6 132 103 1006
(24.5) (10.6) (8.3) (81.1)
82.4 67 31 104
(20.9) (33.2) (15.3) (51.5)
79.2 52 32 41
(21.9) (41.6) (25.6) (32.8)
102 66 237 1163
(6.5) (4.2) (15.1) (74.2)
38 61 229 913
(3.1) (4.9) (18.5) (73.6)
45 3 5 149
(22.3) (1.5) (2.5) (73.8)
19 2 3 101
(15.2) (1.6) (2.4) (80.8)
3.3 626 912 30 4.7 2.2 3.5 1.6
(2.1) (39.9) (58.2) (1.9) (0-34) (0-15) (0-9) (0-6)
3.1 454 778 9 4.2 0 3.4 0
(2) (36.6) (62.7) (0.7) (0-30) (0) (0-9) (0)
4.2 124 76 2 6.8 2.0 3.8 0
(2.4) (61.4) (37.6) (1) (1-34) (1-13) (0-8) (0)
3.6 48 58 19 5.2 2.7 4.0 1.6
(2.4) (38.4) (46.4) (15.2) (1-20) (1-15) (1-9) (1-6)
Radiation Oncology biology
physics
www.redjournal.org
Clinical Investigation
Nodal Stage of Surgically Resected Non-Small Cell Lung Cancer and Its Effect on Recurrence Patterns and Overall Survival John M. Varlotto, MD,* Aaron N. Yao, PhD,y Malcolm M. DeCamp, MD,z,x Satvik Ramakrishna, MD,x Abe Recht, MD,jj John Flickinger, MD,{ Adin Andrei, PhD,# Michael F. Reed, MD,**,yy Jennifer W. Toth, MD,**,zz Thomas J. Fizgerald, MD,* Kristin Higgins, MD,xx Xiao Zheng, PhD,y Julie Shelkey, MD,jjjj Laura N. Medford-Davis, MD,{{ Chandra Belani, MD,## and Christopher R. Kelsey, MD*** *Department of Radiation Oncology, University of Massachusetts Medical Center, Worcester, Massachusetts; yDepartment of Healthcare Policy and Research, Virginia Commonwealth University, Richmond, Virginia; zDivision of Thoracic Surgery, Department of Surgery, Northwestern Memorial Hospital, Chicago, Illinois; xNorthwestern University School of Medicine, Chicago, Illinois; jjDepartment of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts; {Department of Radiation Oncology, Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; #Northwestern University, Chicago, Illinois; **Pennsylvania State University College of Medicine, Hershey, Pennsylvania; yyHeart and Vascular Institute, Pennsylvania State University-Hershey, Hershey, Pennsylvania; zzDivision of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Pennsylvania State University-Hershey, Hershey, Pennsylvania; xxDepartment of Radiation Oncology, Emory University, Atlanta, Georgia; jjjjDepartment of Anesthesiology, Columbia University, New York, New York; {{ Department of Emergency Medicine, Baylor College of Medicine, Houston, Texas; ##Pennsylvania State University-Hershey Cancer Institute, Hershey, Pennsylvania; and ***Department of Radiation Oncology, Duke University Cancer Institute, Durham, North Carolina Received Jul 28, 2014, and in revised form Dec 8, 2014. Accepted for publication Dec 11, 2014.
Summary Nodal stage of surgically resected non-small cell lung cancer is related to distal recurrence and overall survival, but not local recurrence.
Purpose: Current National Comprehensive Cancer Network guidelines recommend postoperative radiation therapy (PORT) for patients with resected non-small cell lung cancer (NSCLC) with N2 involvement. We investigated the relationship between nodal stage and local-regional recurrence (LR), distant recurrence (DR) and overall survival (OS) for patients having an R0 resection. Methods and Materials: A multi-institutional database of consecutive patients undergoing R0 resection for stage I-IIIA NSCLC from 1995 to 2008 was used. Patients receiving any radiation therapy before relapse were excluded. A total of 1241, 202,
Reprint requests to: John M. Varlotto, MD, University of Massachusetts, Health Alliance Medical Center, 275 Nichols St, Fitchburg, MA 01420. E-mail: [email protected] Int J Radiation Oncol Biol Phys, Vol. 91, No. 4, pp. 765e773, 2015 0360-3016/$ - see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ijrobp.2014.12.028
Dr Yao was supported by National Cancer Institute grant 2R25CA093423. Conflict of interest: none.
766
International Journal of Radiation Oncology Biology Physics
Varlotto et al.
and 125 patients were identified with N0, N1, and N2 involvement, respectively; 161 patients received chemotherapy. Cumulative incidence rates were calculated for LR and DR as first sites of failure, and Kaplan-Meier estimates were made for OS. Competing risk analysis and proportional hazards models were used to examine LR, DR, and OS. Independent variables included age, sex, surgical procedure, extent of lymph node sampling, histology, lymphatic or vascular invasion, tumor size, tumor grade, chemotherapy, nodal stage, and visceral pleural invasion. Results: The median follow-up time was 28.7 months. Patients with N1 or N2 nodal stage had rates of LR similar to those of patients with N0 disease, but were at significantly increased risk for both DR (N1, hazard ratio [HR] Z 1.84, 95% confidence interval [CI]: 1.30-2.59; PZ.001; N2, HR Z 2.32, 95% CI: 1.55-3.48; P70 Predicted 70 Predicted Unknown Type of surgery Pneumonectomy Segmentectomy Wedge Bilobectomy Tumor size Mean (SD) >3 cm 3 cm Unknown No. of hilar/intralobar LNs removed (range) No. of hilar/intralobar LNs involved (range) No. of med LNs removed (range) No. of med LNs involved (range) Adjuvant chemotherapy Yes No Histology Adenocarcinoma Adenosquamous Bronchoalveolar carcinoma Large-cell cancer NSCLC-NOS Squamous cell Unknown Grade 1
67.1 (9.7)
67.5 (9.7)
65.8 (9.2)
65 (9.9)
848 (54.1) 720 (45.9)
648 (52.2) 593 (47.8)
132 (65.4) 70 (34.7)
68 (54.4) 57 (45.6)
200 (12.8) 1362 (86.9) 6 (0.4)
154 (12.4) 1084 (87.4) 3 (0.2)
28 (13.9) 173 (85.6) 1 (0.5)
18 (14.4) 105 (84) 2 (1.6)
P value .003 .002
.18
.012 210 442 244 71 574 27
(13.4) (28.2) (15.6) (4.5) (36.6) (1.7)
167 351 189 59 465 10
(13.5) (28.3) (15.2) (4.8) (37.5) (0.8)
25 59 36 7 69 6
(12.4) (29.2) (17.8) (3.5) (34.2) (3)
18 36 19 5 40 7
(14.4) (28.8) (15.2) (4) (32) (5.6)
67.9 181 328 1059
(20.3) (11.5) (20.9) (67.5)
66.8 104 199 938
(21.6) (8.4) (16) (75.6)
69 42 70 90
(18.6) (20.8) (34.7) (44.6)
70.3 35 59 31
(17.9) (28) (47.2) (24.8)
2 209 259 1100
(0.7) (13.3) (16.5) (70.2)
1.9 110 163 968
(0.8) (8.9) (13.1) (78)
2.1 50 58 94
(0.7) (24.8) (28.7) (46.5)
2.2 49 38 38
(0.7) (39.2) (30.4) (30.4)
78.5 251 166 1151
(23.2) (16) (10.6) (73.4)
76.6 132 103 1006
(24.5) (10.6) (8.3) (81.1)
82.4 67 31 104
(20.9) (33.2) (15.3) (51.5)
79.2 52 32 41
(21.9) (41.6) (25.6) (32.8)
102 66 237 1163
(6.5) (4.2) (15.1) (74.2)
38 61 229 913
(3.1) (4.9) (18.5) (73.6)
45 3 5 149
(22.3) (1.5) (2.5) (73.8)
19 2 3 101
(15.2) (1.6) (2.4) (80.8)
3.3 626 912 30 4.7 2.2 3.5 1.6
(2.1) (39.9) (58.2) (1.9) (0-34) (0-15) (0-9) (0-6)
3.1 454 778 9 4.2 0 3.4 0
(2) (36.6) (62.7) (0.7) (0-30) (0) (0-9) (0)
4.2 124 76 2 6.8 2.0 3.8 0
(2.4) (61.4) (37.6) (1) (1-34) (1-13) (0-8) (0)
3.6 48 58 19 5.2 2.7 4.0 1.6
(2.4) (38.4) (46.4) (15.2) (1-20) (1-15) (1-9) (1-6)
