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Effect of Tumor Volume Doubling Time on Prognosis for Stage I Non–small Cell Lung Cancers
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Volume 99 Number 2S Supplement 2017 Author Disclosure: A. Nikolaev: None. R.K. Benda: None. C.Y. Shang: None. M.E. Kasper: None. T.R. Williams: None.
3153 Effect of Tumor Volume Doubling Time on Prognosis for Stage I Nonesmall Cell Lung Cancers H. No,1 H.M. Gagne,2 C.J. Nelson,2 M. Kinsey,3 G. Garrison,3 J. Kikut,4 G. Gentchos,5 D. Seward,6 N. Sidiropoulos,6 E. Folefac,7 B. Leavitt,8 T. Ashikaga,9 K. Dragnev,10 S.H. Lin,11 and C.J. Anker2; 1The University of Vermont Robert Larner MD College of Medicine, Burlington, VT, 2 Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, VT, 3Division of Pulmonary and Critical Care Medicine, University of Vermont Medical Center, Burlington, VT, 4Nuclear Medicine and Diagnostic Radiology, University of Vermont Medical Center, Burlington, VT, 5Department of Radiology, University of Vermont Medical Center, Burlington, VT, 6Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT, 7 Department of Hematology and Oncology, University of Vermont Cancer Center, Burlington, VT, 8Division of Cardiothoracic Surgery, University of Vermont Medical Center, Burlington, VT, 9College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT, 10Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 11Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Computed tomography (CT)-based screening has been found to improve overall survival (OS) by detecting earlier stage non-small cell lung cancers (NSCLC); however, some tumors may exhibit indolent growth and additional prognostic indicators are needed for treatment management decisions. The literature suggests that lung cancers with volume doubling times (VDTs) 400 days might be overdiagnosed. We hypothesized better outcomes would be associated with longer VDTs. Materials/Methods: A retrospective review identified 172 consecutive patients from XXXX with Stage I NSCLC diagnosed between January 2010 - December 2012, of whom 37 met the following additional criteria for this study: 1 year follow-up and 3 month interval between 2 CT scans prior to treatment. Collected data included patient demographics, stage, operability status, histology, Karnofsky Performance Score, Charlson-Deyo Comorbidity Index (CDCI) grades, smoking status, and tumor size changes. VDTs were calculated using a modified Schwartz equation for exponential growth from CT-derived tumor measurements. Estimates of recurrence-free survival (RFS) and OS were calculated from the date of biopsy using the KaplaneMeier method. Univariate Cox proportional hazards models for RFS and OS were evaluated, with significance defined as p<0.05. Results: Median follow-up for all patients was 60.4 months, and the median time between analyzed scans was 10.2 months. The median age was 71 years (range, 46 - 86), with a median KPS of 70 and all patients having a CDCI 1. Fifty-nine percent (nZ22) of the patients were female and 54% (nZ20) exhibited VDTs 400 days. Seventy eight percent (nZ29) were diagnosed with adenocarcinoma, 14% squamous cell, and 8% were not specified. Regarding treatment, 59% (nZ22) underwent surgery, 24% received radiation, 11% received radiofrequency ablation, and 5% were observed. Improved RFS was significantly associated with a VDT 400 days (pZ0.003), with a 5-year RFS of 100% vs. 57%. Fourteen percent (nZ5) recurred locally and 1 patient had distant failure, all with VDTs <400 days. No other investigated factor was significantly associated with either OS or RFS, but 5-year OS was 74% vs. 62% (pZ0.34) for patients with VDTs 400 and <400, respectively. Conclusion: Longer VDT (‡400 days) was associated with significantly improved RFS. Results suggest patients with longer VDTs have a better prognosis and perhaps less aggressive management may be taken, such as an active surveillance approach. Prospective studies with an emphasis on cause-specific survival are warranted to investigate whether it is safe to delay or avoid biopsy and treatment of indolent lesions.
Author Disclosure: H. No: Research Grant; Northern New England Clinical Oncology Society. H.M. Gagne: None. C.J. Nelson: Travel Expenses; Elekta. M. Kinsey: None. G. Garrison: Research Grant; Northern New England Clinical Oncology Society. J. Kikut: Research Grant; Northern New England Clinical Oncology Society. G. Gentchos: None. D. Seward: None. N. Sidiropoulos: Research Grant; Northern New England Clinical Oncology Society. E. Folefac: None. B. Leavitt: Research Grant; Northern New England Clinical Oncology Society. T. Ashikaga: None. K. Dragnev: Consultant; Borhringer Ingelheim. S.H. Lin: Research Grant; Elekta, Inc, Hitachi Chemical, Inc, Peregrine Pharmaceuticals, Inc, Roche/Genentech, STCube Pharmaceuticals, Inc. C.J. Anker: Research Grant; Northern New England Clinical Oncology Society.
3154 Local Tumor Control After Stereotactic Body Radiation Therapy for Early Lung Cancer is Not Impacted by the Use of Intensity Modulated Radiation Therapy or Respiratory Gating T. Nsouli, J. Frandina, S. Tanny, R. Chaudhari, P. Rosenbaum, M.D. Mix, J.A. Bogart, and P.D. Aridgides; SUNY Upstate Medical University, Syracuse, NY Purpose/Objective(s): Though stereotactic body radiation therapy (SBRT) has become a standard treatment option for stage I NSCLC, the majority of published results relate to three-dimensional treatment planning (3D-CRT). Less data is available following treatment with IMRT, and there is also limited published experience using respiratory gating, where treatment is only delivered to a portion of the breathing cycle, during SBRT. Materials/Methods: Retrospective review of patients treated with SBRT for Stage I NSCLC between 2007 and 2015. All patients had a 4D simulation with the Varian RPMTM system and abdominal compression was used in the majority (81%). Respiratory gating was typically used if longitudinal tumor motion exceeded 1cm. Patient characteristics, treatment planning and delivery parameters, dosimetry information, and patient outcomes were collected and analyzed using SPSS statistical software (descriptive stats, bivariate procedures and survival analyses). Results: A total of 297 patients (median age 71, range 43-89) with stage I NSCLC were included. Pathology was confirmed in 94.6% of patients. The majority of lesions were located in the upper lobes (60.9%) and clinical stage T1A (68%). The use of 3DCRT and IMRT planning was similar, 52% vs 48%, although an increased frequency of IMRT was noted in more recent years. Respiratory gating was employed in approximately 16% of cases (nZ51). The gating cohort included 78% lower lobe tumors, while 26% of lesions treated without gating were in the lower lobes. The most common SBRT regimens were 48Gy in 4 fractions and 54-60Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local tumor relapse was similar in patients treated with 3DCRT and IMRT (6.5% vs 4.9%, pZ0.962), and relapse likewise was similar with and without respiratory gating (7.8% vs 4.9%, pZ0.560). In addition, Tstage, tumor size, pathology and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment appeared tolerated well with 6 documented grade 3+ events, and thus there were too few events to compare toxicity amongst treatment cohorts. Conclusion: The utilization of respiratory gating or the use of IMRT does not appear to compromise the therapeutic ratio for patients treated with SBRT for stage I NSCLC. Author Disclosure: T. Nsouli: None. J. Frandina: None. S. Tanny: None. R. Chaudhari: None. P. Rosenbaum: None. M.D. Mix: None. J.A. Bogart: Partner; Upstate University Radiation Oncology. Travel Expenses; Alliance Clinical Trials. Chair, radiation oncology committee; Alliance. P.D. Aridgides: None.
Volume 99 Number 2S Supplement 2017 Author Disclosure: A. Nikolaev: None. R.K. Benda: None. C.Y. Shang: None. M.E. Kasper: None. T.R. Williams: None.
3153 Effect of Tumor Volume Doubling Time on Prognosis for Stage I Nonesmall Cell Lung Cancers H. No,1 H.M. Gagne,2 C.J. Nelson,2 M. Kinsey,3 G. Garrison,3 J. Kikut,4 G. Gentchos,5 D. Seward,6 N. Sidiropoulos,6 E. Folefac,7 B. Leavitt,8 T. Ashikaga,9 K. Dragnev,10 S.H. Lin,11 and C.J. Anker2; 1The University of Vermont Robert Larner MD College of Medicine, Burlington, VT, 2 Division of Radiation Oncology, University of Vermont Cancer Center, Burlington, VT, 3Division of Pulmonary and Critical Care Medicine, University of Vermont Medical Center, Burlington, VT, 4Nuclear Medicine and Diagnostic Radiology, University of Vermont Medical Center, Burlington, VT, 5Department of Radiology, University of Vermont Medical Center, Burlington, VT, 6Department of Pathology and Laboratory Medicine, University of Vermont Medical Center, Burlington, VT, 7 Department of Hematology and Oncology, University of Vermont Cancer Center, Burlington, VT, 8Division of Cardiothoracic Surgery, University of Vermont Medical Center, Burlington, VT, 9College of Engineering and Mathematical Sciences, University of Vermont, Burlington, VT, 10Norris Cotton Cancer Center, Dartmouth-Hitchcock Medical Center, Lebanon, NH, 11Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX Purpose/Objective(s): Computed tomography (CT)-based screening has been found to improve overall survival (OS) by detecting earlier stage non-small cell lung cancers (NSCLC); however, some tumors may exhibit indolent growth and additional prognostic indicators are needed for treatment management decisions. The literature suggests that lung cancers with volume doubling times (VDTs) 400 days might be overdiagnosed. We hypothesized better outcomes would be associated with longer VDTs. Materials/Methods: A retrospective review identified 172 consecutive patients from XXXX with Stage I NSCLC diagnosed between January 2010 - December 2012, of whom 37 met the following additional criteria for this study: 1 year follow-up and 3 month interval between 2 CT scans prior to treatment. Collected data included patient demographics, stage, operability status, histology, Karnofsky Performance Score, Charlson-Deyo Comorbidity Index (CDCI) grades, smoking status, and tumor size changes. VDTs were calculated using a modified Schwartz equation for exponential growth from CT-derived tumor measurements. Estimates of recurrence-free survival (RFS) and OS were calculated from the date of biopsy using the KaplaneMeier method. Univariate Cox proportional hazards models for RFS and OS were evaluated, with significance defined as p<0.05. Results: Median follow-up for all patients was 60.4 months, and the median time between analyzed scans was 10.2 months. The median age was 71 years (range, 46 - 86), with a median KPS of 70 and all patients having a CDCI 1. Fifty-nine percent (nZ22) of the patients were female and 54% (nZ20) exhibited VDTs 400 days. Seventy eight percent (nZ29) were diagnosed with adenocarcinoma, 14% squamous cell, and 8% were not specified. Regarding treatment, 59% (nZ22) underwent surgery, 24% received radiation, 11% received radiofrequency ablation, and 5% were observed. Improved RFS was significantly associated with a VDT 400 days (pZ0.003), with a 5-year RFS of 100% vs. 57%. Fourteen percent (nZ5) recurred locally and 1 patient had distant failure, all with VDTs <400 days. No other investigated factor was significantly associated with either OS or RFS, but 5-year OS was 74% vs. 62% (pZ0.34) for patients with VDTs 400 and <400, respectively. Conclusion: Longer VDT (‡400 days) was associated with significantly improved RFS. Results suggest patients with longer VDTs have a better prognosis and perhaps less aggressive management may be taken, such as an active surveillance approach. Prospective studies with an emphasis on cause-specific survival are warranted to investigate whether it is safe to delay or avoid biopsy and treatment of indolent lesions.
Author Disclosure: H. No: Research Grant; Northern New England Clinical Oncology Society. H.M. Gagne: None. C.J. Nelson: Travel Expenses; Elekta. M. Kinsey: None. G. Garrison: Research Grant; Northern New England Clinical Oncology Society. J. Kikut: Research Grant; Northern New England Clinical Oncology Society. G. Gentchos: None. D. Seward: None. N. Sidiropoulos: Research Grant; Northern New England Clinical Oncology Society. E. Folefac: None. B. Leavitt: Research Grant; Northern New England Clinical Oncology Society. T. Ashikaga: None. K. Dragnev: Consultant; Borhringer Ingelheim. S.H. Lin: Research Grant; Elekta, Inc, Hitachi Chemical, Inc, Peregrine Pharmaceuticals, Inc, Roche/Genentech, STCube Pharmaceuticals, Inc. C.J. Anker: Research Grant; Northern New England Clinical Oncology Society.
3154 Local Tumor Control After Stereotactic Body Radiation Therapy for Early Lung Cancer is Not Impacted by the Use of Intensity Modulated Radiation Therapy or Respiratory Gating T. Nsouli, J. Frandina, S. Tanny, R. Chaudhari, P. Rosenbaum, M.D. Mix, J.A. Bogart, and P.D. Aridgides; SUNY Upstate Medical University, Syracuse, NY Purpose/Objective(s): Though stereotactic body radiation therapy (SBRT) has become a standard treatment option for stage I NSCLC, the majority of published results relate to three-dimensional treatment planning (3D-CRT). Less data is available following treatment with IMRT, and there is also limited published experience using respiratory gating, where treatment is only delivered to a portion of the breathing cycle, during SBRT. Materials/Methods: Retrospective review of patients treated with SBRT for Stage I NSCLC between 2007 and 2015. All patients had a 4D simulation with the Varian RPMTM system and abdominal compression was used in the majority (81%). Respiratory gating was typically used if longitudinal tumor motion exceeded 1cm. Patient characteristics, treatment planning and delivery parameters, dosimetry information, and patient outcomes were collected and analyzed using SPSS statistical software (descriptive stats, bivariate procedures and survival analyses). Results: A total of 297 patients (median age 71, range 43-89) with stage I NSCLC were included. Pathology was confirmed in 94.6% of patients. The majority of lesions were located in the upper lobes (60.9%) and clinical stage T1A (68%). The use of 3DCRT and IMRT planning was similar, 52% vs 48%, although an increased frequency of IMRT was noted in more recent years. Respiratory gating was employed in approximately 16% of cases (nZ51). The gating cohort included 78% lower lobe tumors, while 26% of lesions treated without gating were in the lower lobes. The most common SBRT regimens were 48Gy in 4 fractions and 54-60Gy in 3 fractions. With a median follow up of 22.7 months, there were 17 local failures for a crude relapse rate of 5.7%. Local tumor relapse was similar in patients treated with 3DCRT and IMRT (6.5% vs 4.9%, pZ0.962), and relapse likewise was similar with and without respiratory gating (7.8% vs 4.9%, pZ0.560). In addition, Tstage, tumor size, pathology and SBRT regimen did not correlate with local tumor control. Overall survival for the entire population approximated 72% at 2 years. Treatment appeared tolerated well with 6 documented grade 3+ events, and thus there were too few events to compare toxicity amongst treatment cohorts. Conclusion: The utilization of respiratory gating or the use of IMRT does not appear to compromise the therapeutic ratio for patients treated with SBRT for stage I NSCLC. Author Disclosure: T. Nsouli: None. J. Frandina: None. S. Tanny: None. R. Chaudhari: None. P. Rosenbaum: None. M.D. Mix: None. J.A. Bogart: Partner; Upstate University Radiation Oncology. Travel Expenses; Alliance Clinical Trials. Chair, radiation oncology committee; Alliance. P.D. Aridgides: None.