GENERAL THORACIC
2024
PENNATHUR ET AL SRS/SBRT/SABR FOR RECURRENT LUNG NEOPLASM
2. Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol 2005;23:3270–8. 3. Zimmerman FB, Molls M, Jeremic B. Treatment of recurrent disease in lung cancer. Semin Surg Oncol 2003;21:122–7. 4. Hung JJ, Hsu WH, Hsieh CC, et al. Post-recurrence survival in completely resected stage I non-small cell lung cancer with local recurrence. Thorax 2009;64:192–6. 5. Pairolero PC, Williams DE, Bergstralh EJ, et al. Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 1984;38:331–6. 6. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995;13:8–10. 7. Hellman S, Weichselbaum RR. Importance of local control in an era of systemic therapy. Nat Clin Pract Oncol 2005;2:60–1. 8. Tree AC, Khoo VS, Eeles RA, et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol 2013;14:e28–37. 9. Luketich JD, Martini N, Ginsberg RJ, Rigberg D, Burt ME. Successful treatment of solitary extracranial metastases from non-small cell lung cancer. Ann Thorac Surg 1995;60:1609–11. 10. Luketich JD, Burt ME. Does resection of adrenal metastases from non–small-cell lung cancer improve survival? Ann Thorac Surg 1996;62:1614–6. 11. Sugimura H, Nichols FC, Yang P, et al. Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Ann Thorac Surg 2007;83:409–18. 12. Song D, Kavanagh B, Benedict SH, Schefter T. Stereotactic body radiation therapy. Rationale, techniques, applications, and optimization. Oncology 2004;18:1419–30. 13. Corbin KS, Hellman S, Weichselbaum RR. Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy. J Clin Oncol 2013;31:1384–90. 14. Pennathur A, Luketich JD, Heron DE, et al. Stereotactic radiosurgery for the treatment of lung neoplasm: experience in 100 consecutive patients. Ann Thorac Surg 2009;88:1594–600. 15. Whyte RI, Crownover R, Murphy MJ, et al. Stereotactic radiosurgery for lung tumors preliminary report of a phase I trial. Ann Thorac Surg 2003;75:1097–101. 16. Pennathur A, Luketich JD, Burton S, et al. Stereotactic radiosurgery for the treatment of lung neoplasm: initial experience. Ann Thorac Surg 2007;83:1820–5. 17. Charlson ME, Pompeii P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal
Ann Thorac Surg 2015;100:2019–25
18. 19.
20. 21.
22.
23. 24.
25.
26.
27.
28.
studies: development and validation. J Chronic Dis 1987;40: 373–83. Okamoto Y, Murakami M, Yoden E, et al. Reirradiation for locally recurrent lung cancer previously treated with radiation therapy. Int J Radiat Oncol Biol Phys 2002;52:390–6. Tada T, Fukuda H, Matsui K, et al. Non-small-cell lung cancer: reirradiation for loco-regional relapse previously treated with radiation therapy. Int J Clin Oncol 2005;10: 247–50. Tada T, Fukuda H, Nakagawa K, et al. Non-small cell lung cancer: radiation therapy for locoregional recurrence after complete resection. Int J Clin Oncol 2005;10:425–8. Lanni TB, Grills IS, Kestin LL, et al. Stereotactic radiotherapy reduces treatment cost while improving overall survival and local control over standard fractioned radiation therapy for medically inoperable non-small-cell lung cancer. Am J Clin Oncol 2011;34:494–8. Mitera G, Swaminath A, Rudoler D, et al. Cost-effectiveness analysis comparing conventional versus stereotactic body radiotherapy for surgically ineligible stage I non-small-cell lung cancer. J Oncol Pract 2014;10:130–6. Hishida T, Nagai K, Yoshida J, et al. Is surgical resection indicated for a solitary non-small cell lung cancer recurrence? J Thorac Cardiovasc Surg 2006;131:838–42. Birim O, Maat APWM, Kappetein AP, Van Meerbeeck JP, Damhuis RAM, Bogers AJ. Validation of the Charlson comorbidity index in patients with operated primary nonsmall cell lung cancer. Eur J Cardiothorac Surg 2003;23:30–4. Onishi H, Araki T, Shirato H, et al. Stereotactic hypofractionated high dose irradiation for stage I nonsmall cell lung carcinoma. Clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer 2004;101:1623–31. Timmerman R, McGarry R, Yiannoutsos C. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable earlystage lung cancer. J Clin Oncol 2006;24:4833–9. Pennathur A, Abbas G, Gooding WE, et al. Image-guided radiofrequency ablation of lung neoplasm in 100 consecutive patients by a thoracic surgical service. Ann Thorac Surg 2009;88:1601–8. Leung VA, DiPetrillo TA, Dupuy DE. Image-guided tumor ablation for the treatment of recurrent non-small cell lung cancer within the radiation field. Eur J Radiol 2011;80:e491–9.
INVITED COMMENTARY Dr Pennathur and colleagues [1] describe an experience with 100 patients who have undergone some degree of stereotactic body radiotherapy (SBRT) subsequent to the initial treatment for a primary lung cancer. Their results indicate that, after a median follow-up of 51 months, they observed a 5-year survival of 31%, lending validation to their conclusion that SBRT may play a role in controlling recurrent or persistent lung cancer after failure of initial therapy. The finding is important, as this treatment modality should serve as an option in our arsenal of therapy for patients with limited pulmonary reserve and complicated oncologic histories. As would be expected with complicated cancer patients, those in this report received a variety of therapies such as radiofrequency ablation, chemotherapy, and SBRT as follow-up therapy for having either failed initial therapy (surgery or combined medical therapy) or manifesting another lesion consistent with recurrent lung cancer. The doses of radiation were varied—31% received
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
20 Gy or less—and this variable appears to be associated with a significantly increased hazard ratio for (decreased) survival compared with 60 Gy in the regression analysis. Although the location of recurrence was not reported to be a significant variable in the regression, it would be important to know whether location played a role in the variability of treatment dose, potentially leading to a surrogate outcome or statistical bias. The vast majority of the patients in this series (87) had bronchopulmonary disease, which we would interpret as parenchymal or stump-related recurrence. The median onset of SBRT was 25 months, from which it could be inferred that in many situations parenchymal lesions could be new, early-stage primary tumors. It would be very interesting to know how many of these were additional ground glass opacities. Indeed, characterization of recurrence is of significant interest to surgeons, because patients with sublobar resection followed by marginal staple line recurrence are very different from patients
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.10.059
with a central stump recurrence that would have required a difficult sleeve or a completion pneumonectomy to resect. At our institution, this group of patients, if inoperable, have been considered for intensity-modulated proton therapy, given the restrictions of SBRT to the hilum [2]. Knowledge of response to SBRT in these specific types of cases in Dr Pennathur’s series would be very useful. Certainly, the expert opinion of the surgeon was critical in the initial decision making for therapeutic direction in all of these cases. The complexity of the patients in this series and the bias that was inherent in how each patient arrived at the final treatment modality once the recurrence was identified must be made apparent to the reader. Overall, we applaud this paper as it elucidates the concept of multimodality therapy with the inclusion of SBRT for patients with complex lung cancer courses. To fully appreciate the applicability of these results, however, more information or future reporting of a more homogeneous population will be required. Finally, an arsenal of local therapies that includes surgery, external beam, proton therapy, and SBRT is extremely useful. Perhaps in the future, tissue analysis for
PENNATHUR ET AL SRS/SBRT/SABR FOR RECURRENT LUNG NEOPLASM
2025
mutational analysis will obviate the need for local salvage strategies. For this reason, in cases where it is feasible, histologic confirmation of disease and tissue analysis should be pursued. Wayne Hofstetter, MD Ara Vaporciyan, MD Department of Thoracic and Cardiovascular Surgery University of Texas, MD Anderson Cancer Center 1400 Pressler Ave, Unit 1489 Houston, TX 77030 e-mail: [email protected]
References 1. Pennathur A, Luketich JD, Heron DE, et al. Stereotactic radiosurgery/stereotactic body radiotherapy for recurrent lung neoplasm: an analysis of outcomes in 100 patients. Ann Thorac Surg 2015;100:2019–25. 2. Timmerman R, McGarry R, Yiannoutsos C, et al. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 2006;24:4833–9.
GENERAL THORACIC
Ann Thorac Surg 2015;100:2019–25
2024
PENNATHUR ET AL SRS/SBRT/SABR FOR RECURRENT LUNG NEOPLASM
2. Pisters KM, Le Chevalier T. Adjuvant chemotherapy in completely resected non-small-cell lung cancer. J Clin Oncol 2005;23:3270–8. 3. Zimmerman FB, Molls M, Jeremic B. Treatment of recurrent disease in lung cancer. Semin Surg Oncol 2003;21:122–7. 4. Hung JJ, Hsu WH, Hsieh CC, et al. Post-recurrence survival in completely resected stage I non-small cell lung cancer with local recurrence. Thorax 2009;64:192–6. 5. Pairolero PC, Williams DE, Bergstralh EJ, et al. Postsurgical stage I bronchogenic carcinoma: morbid implications of recurrent disease. Ann Thorac Surg 1984;38:331–6. 6. Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol 1995;13:8–10. 7. Hellman S, Weichselbaum RR. Importance of local control in an era of systemic therapy. Nat Clin Pract Oncol 2005;2:60–1. 8. Tree AC, Khoo VS, Eeles RA, et al. Stereotactic body radiotherapy for oligometastases. Lancet Oncol 2013;14:e28–37. 9. Luketich JD, Martini N, Ginsberg RJ, Rigberg D, Burt ME. Successful treatment of solitary extracranial metastases from non-small cell lung cancer. Ann Thorac Surg 1995;60:1609–11. 10. Luketich JD, Burt ME. Does resection of adrenal metastases from non–small-cell lung cancer improve survival? Ann Thorac Surg 1996;62:1614–6. 11. Sugimura H, Nichols FC, Yang P, et al. Survival after recurrent nonsmall-cell lung cancer after complete pulmonary resection. Ann Thorac Surg 2007;83:409–18. 12. Song D, Kavanagh B, Benedict SH, Schefter T. Stereotactic body radiation therapy. Rationale, techniques, applications, and optimization. Oncology 2004;18:1419–30. 13. Corbin KS, Hellman S, Weichselbaum RR. Extracranial oligometastases: a subset of metastases curable with stereotactic radiotherapy. J Clin Oncol 2013;31:1384–90. 14. Pennathur A, Luketich JD, Heron DE, et al. Stereotactic radiosurgery for the treatment of lung neoplasm: experience in 100 consecutive patients. Ann Thorac Surg 2009;88:1594–600. 15. Whyte RI, Crownover R, Murphy MJ, et al. Stereotactic radiosurgery for lung tumors preliminary report of a phase I trial. Ann Thorac Surg 2003;75:1097–101. 16. Pennathur A, Luketich JD, Burton S, et al. Stereotactic radiosurgery for the treatment of lung neoplasm: initial experience. Ann Thorac Surg 2007;83:1820–5. 17. Charlson ME, Pompeii P, Ales KL, et al. A new method of classifying prognostic comorbidity in longitudinal
Ann Thorac Surg 2015;100:2019–25
18. 19.
20. 21.
22.
23. 24.
25.
26.
27.
28.
studies: development and validation. J Chronic Dis 1987;40: 373–83. Okamoto Y, Murakami M, Yoden E, et al. Reirradiation for locally recurrent lung cancer previously treated with radiation therapy. Int J Radiat Oncol Biol Phys 2002;52:390–6. Tada T, Fukuda H, Matsui K, et al. Non-small-cell lung cancer: reirradiation for loco-regional relapse previously treated with radiation therapy. Int J Clin Oncol 2005;10: 247–50. Tada T, Fukuda H, Nakagawa K, et al. Non-small cell lung cancer: radiation therapy for locoregional recurrence after complete resection. Int J Clin Oncol 2005;10:425–8. Lanni TB, Grills IS, Kestin LL, et al. Stereotactic radiotherapy reduces treatment cost while improving overall survival and local control over standard fractioned radiation therapy for medically inoperable non-small-cell lung cancer. Am J Clin Oncol 2011;34:494–8. Mitera G, Swaminath A, Rudoler D, et al. Cost-effectiveness analysis comparing conventional versus stereotactic body radiotherapy for surgically ineligible stage I non-small-cell lung cancer. J Oncol Pract 2014;10:130–6. Hishida T, Nagai K, Yoshida J, et al. Is surgical resection indicated for a solitary non-small cell lung cancer recurrence? J Thorac Cardiovasc Surg 2006;131:838–42. Birim O, Maat APWM, Kappetein AP, Van Meerbeeck JP, Damhuis RAM, Bogers AJ. Validation of the Charlson comorbidity index in patients with operated primary nonsmall cell lung cancer. Eur J Cardiothorac Surg 2003;23:30–4. Onishi H, Araki T, Shirato H, et al. Stereotactic hypofractionated high dose irradiation for stage I nonsmall cell lung carcinoma. Clinical outcomes in 245 subjects in a Japanese multiinstitutional study. Cancer 2004;101:1623–31. Timmerman R, McGarry R, Yiannoutsos C. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable earlystage lung cancer. J Clin Oncol 2006;24:4833–9. Pennathur A, Abbas G, Gooding WE, et al. Image-guided radiofrequency ablation of lung neoplasm in 100 consecutive patients by a thoracic surgical service. Ann Thorac Surg 2009;88:1601–8. Leung VA, DiPetrillo TA, Dupuy DE. Image-guided tumor ablation for the treatment of recurrent non-small cell lung cancer within the radiation field. Eur J Radiol 2011;80:e491–9.
INVITED COMMENTARY Dr Pennathur and colleagues [1] describe an experience with 100 patients who have undergone some degree of stereotactic body radiotherapy (SBRT) subsequent to the initial treatment for a primary lung cancer. Their results indicate that, after a median follow-up of 51 months, they observed a 5-year survival of 31%, lending validation to their conclusion that SBRT may play a role in controlling recurrent or persistent lung cancer after failure of initial therapy. The finding is important, as this treatment modality should serve as an option in our arsenal of therapy for patients with limited pulmonary reserve and complicated oncologic histories. As would be expected with complicated cancer patients, those in this report received a variety of therapies such as radiofrequency ablation, chemotherapy, and SBRT as follow-up therapy for having either failed initial therapy (surgery or combined medical therapy) or manifesting another lesion consistent with recurrent lung cancer. The doses of radiation were varied—31% received
Ó 2015 by The Society of Thoracic Surgeons Published by Elsevier
20 Gy or less—and this variable appears to be associated with a significantly increased hazard ratio for (decreased) survival compared with 60 Gy in the regression analysis. Although the location of recurrence was not reported to be a significant variable in the regression, it would be important to know whether location played a role in the variability of treatment dose, potentially leading to a surrogate outcome or statistical bias. The vast majority of the patients in this series (87) had bronchopulmonary disease, which we would interpret as parenchymal or stump-related recurrence. The median onset of SBRT was 25 months, from which it could be inferred that in many situations parenchymal lesions could be new, early-stage primary tumors. It would be very interesting to know how many of these were additional ground glass opacities. Indeed, characterization of recurrence is of significant interest to surgeons, because patients with sublobar resection followed by marginal staple line recurrence are very different from patients
0003-4975/$36.00 http://dx.doi.org/10.1016/j.athoracsur.2015.10.059
with a central stump recurrence that would have required a difficult sleeve or a completion pneumonectomy to resect. At our institution, this group of patients, if inoperable, have been considered for intensity-modulated proton therapy, given the restrictions of SBRT to the hilum [2]. Knowledge of response to SBRT in these specific types of cases in Dr Pennathur’s series would be very useful. Certainly, the expert opinion of the surgeon was critical in the initial decision making for therapeutic direction in all of these cases. The complexity of the patients in this series and the bias that was inherent in how each patient arrived at the final treatment modality once the recurrence was identified must be made apparent to the reader. Overall, we applaud this paper as it elucidates the concept of multimodality therapy with the inclusion of SBRT for patients with complex lung cancer courses. To fully appreciate the applicability of these results, however, more information or future reporting of a more homogeneous population will be required. Finally, an arsenal of local therapies that includes surgery, external beam, proton therapy, and SBRT is extremely useful. Perhaps in the future, tissue analysis for
PENNATHUR ET AL SRS/SBRT/SABR FOR RECURRENT LUNG NEOPLASM
2025
mutational analysis will obviate the need for local salvage strategies. For this reason, in cases where it is feasible, histologic confirmation of disease and tissue analysis should be pursued. Wayne Hofstetter, MD Ara Vaporciyan, MD Department of Thoracic and Cardiovascular Surgery University of Texas, MD Anderson Cancer Center 1400 Pressler Ave, Unit 1489 Houston, TX 77030 e-mail: [email protected]
References 1. Pennathur A, Luketich JD, Heron DE, et al. Stereotactic radiosurgery/stereotactic body radiotherapy for recurrent lung neoplasm: an analysis of outcomes in 100 patients. Ann Thorac Surg 2015;100:2019–25. 2. Timmerman R, McGarry R, Yiannoutsos C, et al. Excessive toxicity when treating central tumors in a phase II study of stereotactic body radiation therapy for medically inoperable early-stage lung cancer. J Clin Oncol 2006;24:4833–9.
GENERAL THORACIC
Ann Thorac Surg 2015;100:2019–25
