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Outcomes after Stereotactic Body Radiation Therapy (SBRT) or Anatomic Surgical Resection (ASR) for Clinical Stage I Non-small Cell Lung Cancer
Proceedings of the 52nd Annual ASTRO Meeting
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Outcomes after Stereotactic Body Radiation Therapy (SBRT) or Anatomic Surgical Resection (ASR) for Clinical Stage I Non-small Cell Lung Cancer
C. G. Robinson, I. El Naqa, T. Crabtree, B. Meyers, V. Puri, J. Zoole, P. Parikh, J. D. Bradley Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): ASR (lobectomy, pneumonectomy) is the standard treatment for medically operable patients with clinical stage I non-small cell lung cancer (NSCLC), while SBRT provides excellent control rates for medically inoperable patients. Limited comparisons have been made between these treatments to date. We reviewed outcomes of patients with clinical stage I NSCLC treated at a single institution with ASR or SBRT. Materials/Methods: From January 2004 to December 2007, 321 patients underwent definitive treatment for histologically confirmed clinical stage I NSCLC with SBRT (n = 75) or ASR (n = 246). SBRT patients received a median dose of 54 Gy in 3 fractions (range, 40-54 Gy in 3-6 fractions). ASR patients primarily underwent lobectomy (n = 226), with the rest undergoing bilobectomy (n = 6) or pneumonectomy (n = 14). Patients were followed with serial CT chest imaging, with PET reserved for evaluation of suspected recurrence. SBRT and ASR were compared with regards to local control (LC), regional control (RC), distant metastases-free survival (DMFS), and overall survival (OS). A propensity-matched analysis (PMA) was also performed, with 46 patients in each group matched for age (\75 vs. .75 years), ACE-27 co-morbidity score (0-1 vs. 2-3), and T-stage (T1 vs. T2). Results: Median follow-up was 33 months (range, 6-71) for ASR and 25 months (range, 6-62) for SBRT. ASR and SBRT groups were balanced for gender (45% vs. 49% female, p = 0.601) and histology (76% vs. 67% non-squamous, p = 0.154). ASR patients were younger (median age 66 vs. 75 years, p \ 0.0001), healthier (median ACE-27 score 1 vs. 2, p \ 0.0001), and had superior pulmonary function (median FEV1 2.02 vs. 1.29 L, p \ 0.0001; DLCO 16.08 vs. 9.7 mL/min/mm Hg, p \ 0.0001). Slightly more patients in the ASR group had T2 tumors (45.5% vs. 29.3%, p = 0.016). Final pathology up-staged 34% of ASR patients, and 21% received adjuvant chemotherapy. No SBRT patients received adjuvant chemotherapy. On direct comparison, 4-year LC (94% vs. 87%, p = 0.016), DMFS (84% vs. 64%, p = 0.006), and OS (68% vs. 34%, p \ 0.0001) favored ASR over SBRT, while RC (88% vs. 81%, p = 0.256) was not significantly different. On PMA, 4-year LC (91% vs. 86%, p = 0.465), RC (81% vs. 79%, p = 0.354), and DMFS (70% vs. 77%, p = 0.924) was similar between ASR and SBRT, though OS remained greater for ASR (57% vs. 33%, p = 0.028). Conclusions: In a direct comparison of outcomes for clinical stage I NSCLC, ASR appears to have superior cancer-specific and overall survival. However, after matching for age, co-morbidity score, and T-stage, SBRT was equivalent to ASR in 4-year LC, RC, and DMFS. Despite equivalent cancer control rates, SBRT patients had inferior OS, perhaps reflecting an excess of non-cancer deaths. Author Disclosure: C.G. Robinson, None; I. El Naqa, None; T. Crabtree, None; B. Meyers, None; V. Puri, None; J. Zoole, None; P. Parikh, None; J.D. Bradley, None.
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A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) Combined with Erlotinib for Patients with Recurrent Non-small Cell Lung Cancer (NSCLC)
B. Kavanagh1, R. Abdulrahman2, D. R. Camidge1, D. E. Gerber2, P. A. Bunn1, J. Schiller2, H. Choy2, L. Gaspar1, R. Doebele1, R. D. Timmerman2 1
University of Colorado School of Medicine, Aurora, CO, 2University of Texas Southwestern, Dallas, TX
Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is a spatially targeted therapy that can ablate metastatic lesions from solid tumors. Erlotinib is an EGFR-inhibitory, molecular-targeted agent that improves overall survival (OS) in recurrent nonsmall cell lung cancer (NSCLC). The objectives of this IRB-approved prospective study were to estimate the six-month progression-free survival (PFS), pattern of failure (POF), and OS for patients treated with SBRT and erlotinib for recurrent NSCLC. Materials/Methods: Eligible patients had #6 measurable, PET-avid extracranial lesions after $1 prior chemotherapy regimen for NSCLC. Subjects received erlotinib (starting dose, 150 mg po/day) followed by SBRT to all active disease sites 1-4 weeks after the initiation of erlotinib. SBRT was given in 1-5 fractions according to guidelines established in prior studies; conservative tumor doses and normal tissue dose constraints were applied. Maintenance erlotinib continued until disease progression or intolerable toxicity. Results: Fifteen patients have been enrolled: 7 female, 8 male; median age, 68 yrs (range, 56-86); $2 prior regimens, n = 6; median number of sites irradiated, 2 (range, 1-5). A total of 30 lesions were treated with SBRT to a median dose of 31.5 Gy in 3 fractions (range, 18-40, 1-5 fractions). One patient treated for adrenal metastasis had serious wound healing complications after salvage surgery for local failure 12 months after treatment. Median follow-up among surviving patients is 10 months. The 6 month PFS was 55%; six-month OS was 77%, and median OS exceeds 12 months. Progression outside of the SBRT field is the dominant POF observed: the six-month rates of freedom from initially involved site or initially uninvolved site progression are 89% and 63%, respectively. Conclusions: The combination of erlotinib and SBRT was well tolerated and shifted the POF away from initially involved sites to predominantly initially uninvolved sites. The PFS and OS compare favorably with reports of erlotinib alone. Larger studies of the novel paradigm of combining molecular-targeted systemic agents and spatially targeted interventions such as SBRT are warranted for specific cancer types. Author Disclosure: B. Kavanagh, None; R. Abdulrahman, None; D.R. Camidge, None; D.E. Gerber, None; P.A. Bunn, None; J. Schiller, Genentech, B. Research Grant; OSI, B. Research Grant; Genentech, F. Consultant/Advisory Board; OSI, F. Consultant/ Advisory Board; H. Choy, None; L. Gaspar, None; R. Doebele, None; R.D. Timmerman, None.
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CT-based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients with Mass-like Consolidation after Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-small Cell Lung Cancer (NSCLC)
N. E. Dunlap, W. Yang, A. McIntosh, K. Sheng, S. H. Benedict, P. W. Read, J. M. Larner University of Virginia, Charlottesville, VA
S15
32
Outcomes after Stereotactic Body Radiation Therapy (SBRT) or Anatomic Surgical Resection (ASR) for Clinical Stage I Non-small Cell Lung Cancer
C. G. Robinson, I. El Naqa, T. Crabtree, B. Meyers, V. Puri, J. Zoole, P. Parikh, J. D. Bradley Washington University School of Medicine, St. Louis, MO Purpose/Objective(s): ASR (lobectomy, pneumonectomy) is the standard treatment for medically operable patients with clinical stage I non-small cell lung cancer (NSCLC), while SBRT provides excellent control rates for medically inoperable patients. Limited comparisons have been made between these treatments to date. We reviewed outcomes of patients with clinical stage I NSCLC treated at a single institution with ASR or SBRT. Materials/Methods: From January 2004 to December 2007, 321 patients underwent definitive treatment for histologically confirmed clinical stage I NSCLC with SBRT (n = 75) or ASR (n = 246). SBRT patients received a median dose of 54 Gy in 3 fractions (range, 40-54 Gy in 3-6 fractions). ASR patients primarily underwent lobectomy (n = 226), with the rest undergoing bilobectomy (n = 6) or pneumonectomy (n = 14). Patients were followed with serial CT chest imaging, with PET reserved for evaluation of suspected recurrence. SBRT and ASR were compared with regards to local control (LC), regional control (RC), distant metastases-free survival (DMFS), and overall survival (OS). A propensity-matched analysis (PMA) was also performed, with 46 patients in each group matched for age (\75 vs. .75 years), ACE-27 co-morbidity score (0-1 vs. 2-3), and T-stage (T1 vs. T2). Results: Median follow-up was 33 months (range, 6-71) for ASR and 25 months (range, 6-62) for SBRT. ASR and SBRT groups were balanced for gender (45% vs. 49% female, p = 0.601) and histology (76% vs. 67% non-squamous, p = 0.154). ASR patients were younger (median age 66 vs. 75 years, p \ 0.0001), healthier (median ACE-27 score 1 vs. 2, p \ 0.0001), and had superior pulmonary function (median FEV1 2.02 vs. 1.29 L, p \ 0.0001; DLCO 16.08 vs. 9.7 mL/min/mm Hg, p \ 0.0001). Slightly more patients in the ASR group had T2 tumors (45.5% vs. 29.3%, p = 0.016). Final pathology up-staged 34% of ASR patients, and 21% received adjuvant chemotherapy. No SBRT patients received adjuvant chemotherapy. On direct comparison, 4-year LC (94% vs. 87%, p = 0.016), DMFS (84% vs. 64%, p = 0.006), and OS (68% vs. 34%, p \ 0.0001) favored ASR over SBRT, while RC (88% vs. 81%, p = 0.256) was not significantly different. On PMA, 4-year LC (91% vs. 86%, p = 0.465), RC (81% vs. 79%, p = 0.354), and DMFS (70% vs. 77%, p = 0.924) was similar between ASR and SBRT, though OS remained greater for ASR (57% vs. 33%, p = 0.028). Conclusions: In a direct comparison of outcomes for clinical stage I NSCLC, ASR appears to have superior cancer-specific and overall survival. However, after matching for age, co-morbidity score, and T-stage, SBRT was equivalent to ASR in 4-year LC, RC, and DMFS. Despite equivalent cancer control rates, SBRT patients had inferior OS, perhaps reflecting an excess of non-cancer deaths. Author Disclosure: C.G. Robinson, None; I. El Naqa, None; T. Crabtree, None; B. Meyers, None; V. Puri, None; J. Zoole, None; P. Parikh, None; J.D. Bradley, None.
33
A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) Combined with Erlotinib for Patients with Recurrent Non-small Cell Lung Cancer (NSCLC)
B. Kavanagh1, R. Abdulrahman2, D. R. Camidge1, D. E. Gerber2, P. A. Bunn1, J. Schiller2, H. Choy2, L. Gaspar1, R. Doebele1, R. D. Timmerman2 1
University of Colorado School of Medicine, Aurora, CO, 2University of Texas Southwestern, Dallas, TX
Purpose/Objective(s): Stereotactic body radiation therapy (SBRT) is a spatially targeted therapy that can ablate metastatic lesions from solid tumors. Erlotinib is an EGFR-inhibitory, molecular-targeted agent that improves overall survival (OS) in recurrent nonsmall cell lung cancer (NSCLC). The objectives of this IRB-approved prospective study were to estimate the six-month progression-free survival (PFS), pattern of failure (POF), and OS for patients treated with SBRT and erlotinib for recurrent NSCLC. Materials/Methods: Eligible patients had #6 measurable, PET-avid extracranial lesions after $1 prior chemotherapy regimen for NSCLC. Subjects received erlotinib (starting dose, 150 mg po/day) followed by SBRT to all active disease sites 1-4 weeks after the initiation of erlotinib. SBRT was given in 1-5 fractions according to guidelines established in prior studies; conservative tumor doses and normal tissue dose constraints were applied. Maintenance erlotinib continued until disease progression or intolerable toxicity. Results: Fifteen patients have been enrolled: 7 female, 8 male; median age, 68 yrs (range, 56-86); $2 prior regimens, n = 6; median number of sites irradiated, 2 (range, 1-5). A total of 30 lesions were treated with SBRT to a median dose of 31.5 Gy in 3 fractions (range, 18-40, 1-5 fractions). One patient treated for adrenal metastasis had serious wound healing complications after salvage surgery for local failure 12 months after treatment. Median follow-up among surviving patients is 10 months. The 6 month PFS was 55%; six-month OS was 77%, and median OS exceeds 12 months. Progression outside of the SBRT field is the dominant POF observed: the six-month rates of freedom from initially involved site or initially uninvolved site progression are 89% and 63%, respectively. Conclusions: The combination of erlotinib and SBRT was well tolerated and shifted the POF away from initially involved sites to predominantly initially uninvolved sites. The PFS and OS compare favorably with reports of erlotinib alone. Larger studies of the novel paradigm of combining molecular-targeted systemic agents and spatially targeted interventions such as SBRT are warranted for specific cancer types. Author Disclosure: B. Kavanagh, None; R. Abdulrahman, None; D.R. Camidge, None; D.E. Gerber, None; P.A. Bunn, None; J. Schiller, Genentech, B. Research Grant; OSI, B. Research Grant; Genentech, F. Consultant/Advisory Board; OSI, F. Consultant/ Advisory Board; H. Choy, None; L. Gaspar, None; R. Doebele, None; R.D. Timmerman, None.
34
CT-based Anatomic Assessment Overestimates Local Tumor Recurrence in Patients with Mass-like Consolidation after Stereotactic Body Radiation Therapy (SBRT) for Early Stage Non-small Cell Lung Cancer (NSCLC)
N. E. Dunlap, W. Yang, A. McIntosh, K. Sheng, S. H. Benedict, P. W. Read, J. M. Larner University of Virginia, Charlottesville, VA
S15