Failure Patterns and Toxicity of Concurrent Proton Therapy and Chemotherapy for Stage III...
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2588 Promising Outcome of Stereotactic Body Radiation Therapy for Old Patients with Inoperable Stage III Non–small Cell Lung Cancer Y. Wang, T. Xia, H. Q. Li, P. Li, Q. X. Sun Air Force General Hospital, Beijing, China Purpose/Objective(s): To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) in old patients (age $65 years) with Stage III non–small-cell lung cancer. Materials/Methods: Forty-nine patients with medically inoperable Stage III non–small-cell lung cancer underwent treatment us- ing the stereotactic gamma-ray whole-body therapy system (Body Gamma-Knife Radiosurgery) with 30 rotary conical-surface Co 60 sources focused on the target volume. Low-speed CT simulation was conducted, which was followed by three-dimensional conformal radiotherapy planning. A total dose of 48 Gy (range, 39–57 Gy) was delivered at 4 Gy/fraction(range, 2.5–6 Gy/fraction) to the 50% isodose line covering the planning target volume of tumor, while a total dose of 41 Gy (range, 30–52 Gy) was delivered at 3.5 Gy/fraction(range, 3–5 Gy/fraction) to the planning target volume of metastatic lymph nodes. SBRT was given with five fractions a week and was completed within three weeks. The objective response was evaluated three to six months at completion of SBRT, overall survival and relapse-free survival was acquired with the median follow-up of 24 months. Results: The objective response rate was 69.4% (complete response: 26.5%, 13/49; partial response: 42.9%, 21/49) and median survival was 22 months. The 1-year, 2-year relapse-free survival rates were 95.5% in all patients. The 1-year, 2-year overall sur- vival rates were 61.2% and 43.0%, respectively. There was no severe pulmonary and esophagus acute radiation reaction. Only 5.3% (1/49) of the patients occurred Grade 3 esophageal late radiation reaction. Conclusions: Body Gamma Knife Therapy with a highly focused SBRT technique resulted in promising local control with min- imal toxicity for old patients (age $65 years) with Stage III inoperable non–small-cell lung cancer. Author Disclosure: Y. Wang, None; T. Xia, None; H.Q. Li, None; P. Li, None; Q.X. Sun, None. 2589 Does Pre-treatment Metabolic Tumor Growth Rate (MTGR) Predict Progression in Lung Cancer? D. V. Eastham 1 , C. H. Chapman 1 , A. K. Rao 1 , B. Narasimhan 2 , A. Quon 3 , M. S. Vasanawala 3 , H. Wakelee 1 , Q. Le 1 , A. D. Colevas 1 , B. W. Loo 1 , et al. 1 Stanford University Cancer Center, Stanford, CA, 2 Department of Health and Research Policy, Stanford, CA, 3 Department of Nuclear Medicine, Stanford, CA Purpose/Objective(s): We previously reported that pretreatment metabolic tumor volume (MTV) measured by FDG-PET is a strong prognostic factor in patients with lung cancer treated by radiation therapy (most with concurrent chemotherapy). Metabolic tumor growth rate (MTGR) measured by serial PET imaging is a dynamic assessment that may be a more sensitive indicator of biological tumor aggressiveness. We conducted an exploratory study to quantify pre-treatment MTGR in patients with lung cancer treated with radiation therapy to see if pre-treatment MTGR was predictive of time to progression (TTP). Materials/Methods: We identified patients with lung cancer who had both a treatment planning PET-CT and a prior diagnostic PET-CT. Inclusion criteria were patients with newly diagnosed lung cancer, treated with curative intent with radiotherapy (+/- che- motherapy), who received no treatment between the two pre-treatment scans. MTV was segmented on each scan using semi-au- tomated software employing an intensity gradient-based algorithm to define the edges of the metabolically active regions. Results: Of 187 patients with two pretreatment scans, 39 met inclusion criteria. Median interval between the two scans was 4.2 weeks. The median total body MTV increase between scans was 23.6%; 6 of 39 had over 100% increases. Median total body MTGR was 6.0% per week (range, -5.7% to 38.5% per week). 11 of 39 patients (28.2%) had a MTGR greater than 10% per week. Median follow-up time was 46.5 weeks and 18 of 39 patients had progression events at the time of this analysis. A Cox proportional model of this preliminary data showed no association between the TTP and MTGR (p value 0.42). Conclusions: MTGR may reflect tumor biology more accurately than static measures of tumor size. Approximately 1/3 of the pa- tients in this cohort had MTGR greater than 10% per week, indicating that clinically significant growth was occurring during the pretreatment interval. Preliminary analysis of our data after a median of 46.5 weeks of follow-up demonstrates that MTGR has no statistically significant association with TTP. The strength of this analysis is limited by only 18 progression events to date. It is possible that the complexity of growth kinetics may blur any association between progression and MTGR. Smaller tumors which have a greater likelihood of cure may be undergoing exponential growth kinetics while larger tumors which are more likely to prog- ress may be growing at a less than exponential rate due to environmental constraints. Gompertzian growth kinetics produces higher growth rates in smaller, more curable tumors, and vice versa, making it difficult to disentangle the effects of biological aggressive- ness and absolute tumor burden. Data will be re-analyzed after more progression events have occurred to clarify a possible asso- ciation with MTGR. Author Disclosure: D.V. Eastham, None; C.H. Chapman, None; A.K. Rao, None; B. Narasimhan, None; A. Quon, None; M.S. Vasanawala, None; H. Wakelee, None; Q. Le, None; A.D. Colevas, None; B.W. Loo, Dr. Billy Loo has received honoraria from Varian Medical Systems, Inc., Accuray, Inc., General Electric Healthcare, and CyberHeart, Inc., D. Speakers Bureau/ Honoraria. 2590 Failure Patterns and Toxicity of Concurrent Proton Therapy and Chemotherapy for Stage III Non–small Cell Lung Cancer J. Y. Chang, R. Komaki, M. K. Bucci, C. Lu, H. Y. Wen, B. DeGracia, M. Gillin, R. Mohan, J. D. Cox The University of Texas M. D. Anderson Cancer Center, Houston, TX Purpose/Objective(s): Local failure rates after conventional photon therapy (60 Gy) for non–small cell lung cancer (NSCLC) ex- ceed 50%. Dose escalation can improve local control and potentially survival but toxicity is significant, particularly when S446 I. J. Radiation Oncology d Biology d Physics Volume 75, Number 3, Supplement, 2009
Transcript of Failure Patterns and Toxicity of Concurrent Proton Therapy and Chemotherapy for Stage III...
S446 I. J. Radiation Oncology d Biology d Physics Volume 75, Number 3, Supplement, 2009
2588 Promising Outcome of Stereotactic Body Radiation Therapy for Old Patients with Inoperable Stage III
Non–small Cell Lung CancerY. Wang, T. Xia, H. Q. Li, P. Li, Q. X. Sun
Air Force General Hospital, Beijing, China
Purpose/Objective(s): To evaluate the efficacy and toxicity of hypofractionated stereotactic body radiotherapy (SBRT) in oldpatients (age $65 years) with Stage III non–small-cell lung cancer.
Materials/Methods: Forty-nine patients with medically inoperable Stage III non–small-cell lung cancer underwent treatment us-ing the stereotactic gamma-ray whole-body therapy system (Body Gamma-Knife Radiosurgery) with 30 rotary conical-surfaceCo60 sources focused on the target volume. Low-speed CT simulation was conducted, which was followed by three-dimensionalconformal radiotherapy planning. A total dose of 48 Gy (range, 39–57 Gy) was delivered at 4 Gy/fraction(range, 2.5–6 Gy/fraction)to the 50% isodose line covering the planning target volume of tumor, while a total dose of 41 Gy (range, 30–52 Gy) was deliveredat 3.5 Gy/fraction(range, 3–5 Gy/fraction) to the planning target volume of metastatic lymph nodes. SBRT was given with fivefractions a week and was completed within three weeks. The objective response was evaluated three to six months at completionof SBRT, overall survival and relapse-free survival was acquired with the median follow-up of 24 months.
Results: The objective response rate was 69.4% (complete response: 26.5%, 13/49; partial response: 42.9%, 21/49) and mediansurvival was 22 months. The 1-year, 2-year relapse-free survival rates were 95.5% in all patients. The 1-year, 2-year overall sur-vival rates were 61.2% and 43.0%, respectively. There was no severe pulmonary and esophagus acute radiation reaction. Only5.3% (1/49) of the patients occurred Grade 3 esophageal late radiation reaction.
Conclusions: Body Gamma Knife Therapy with a highly focused SBRT technique resulted in promising local control with min-imal toxicity for old patients (age $65 years) with Stage III inoperable non–small-cell lung cancer.
Author Disclosure: Y. Wang, None; T. Xia, None; H.Q. Li, None; P. Li, None; Q.X. Sun, None.
2589 Does Pre-treatment Metabolic Tumor Growth Rate (MTGR) Predict Progression in Lung Cancer?
D. V. Eastham1, C. H. Chapman1, A. K. Rao1, B. Narasimhan2, A. Quon3, M. S. Vasanawala3, H. Wakelee1, Q. Le1,A. D. Colevas1, B. W. Loo1, et al.1Stanford University Cancer Center, Stanford, CA, 2Department of Health and Research Policy, Stanford, CA, 3Department ofNuclear Medicine, Stanford, CA
Purpose/Objective(s): We previously reported that pretreatment metabolic tumor volume (MTV) measured by FDG-PET isa strong prognostic factor in patients with lung cancer treated by radiation therapy (most with concurrent chemotherapy). Metabolictumor growth rate (MTGR) measured by serial PET imaging is a dynamic assessment that may be a more sensitive indicator ofbiological tumor aggressiveness. We conducted an exploratory study to quantify pre-treatment MTGR in patients with lung cancertreated with radiation therapy to see if pre-treatment MTGR was predictive of time to progression (TTP).
Materials/Methods: We identified patients with lung cancer who had both a treatment planning PET-CT and a prior diagnosticPET-CT. Inclusion criteria were patients with newly diagnosed lung cancer, treated with curative intent with radiotherapy (+/- che-motherapy), who received no treatment between the two pre-treatment scans. MTV was segmented on each scan using semi-au-tomated software employing an intensity gradient-based algorithm to define the edges of the metabolically active regions.
Results: Of 187 patients with two pretreatment scans, 39 met inclusion criteria. Median interval between the two scans was 4.2weeks. The median total body MTV increase between scans was 23.6%; 6 of 39 had over 100% increases. Median total bodyMTGR was 6.0% per week (range, -5.7% to 38.5% per week). 11 of 39 patients (28.2%) had a MTGR greater than 10% perweek. Median follow-up time was 46.5 weeks and 18 of 39 patients had progression events at the time of this analysis. A Coxproportional model of this preliminary data showed no association between the TTP and MTGR (p value 0.42).
Conclusions: MTGR may reflect tumor biology more accurately than static measures of tumor size. Approximately 1/3 of the pa-tients in this cohort had MTGR greater than 10% per week, indicating that clinically significant growth was occurring during thepretreatment interval. Preliminary analysis of our data after a median of 46.5 weeks of follow-up demonstrates that MTGR has nostatistically significant association with TTP. The strength of this analysis is limited by only 18 progression events to date. It ispossible that the complexity of growth kinetics may blur any association between progression and MTGR. Smaller tumors whichhave a greater likelihood of cure may be undergoing exponential growth kinetics while larger tumors which are more likely to prog-ress may be growing at a less than exponential rate due to environmental constraints. Gompertzian growth kinetics produces highergrowth rates in smaller, more curable tumors, and vice versa, making it difficult to disentangle the effects of biological aggressive-ness and absolute tumor burden. Data will be re-analyzed after more progression events have occurred to clarify a possible asso-ciation with MTGR.
Author Disclosure: D.V. Eastham, None; C.H. Chapman, None; A.K. Rao, None; B. Narasimhan, None; A. Quon, None; M.S.Vasanawala, None; H. Wakelee, None; Q. Le, None; A.D. Colevas, None; B.W. Loo, Dr. Billy Loo has received honorariafrom Varian Medical Systems, Inc., Accuray, Inc., General Electric Healthcare, and CyberHeart, Inc., D. Speakers Bureau/Honoraria.
2590 Failure Patterns and Toxicity of Concurrent Proton Therapy and Chemotherapy for Stage III Non–small
Cell Lung CancerJ. Y. Chang, R. Komaki, M. K. Bucci, C. Lu, H. Y. Wen, B. DeGracia, M. Gillin, R. Mohan, J. D. Cox
The University of Texas M. D. Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Local failure rates after conventional photon therapy (60 Gy) for non–small cell lung cancer (NSCLC) ex-ceed 50%. Dose escalation can improve local control and potentially survival but toxicity is significant, particularly when
Proceedings of the 51st Annual ASTRO Meeting S447
concurrent chemotherapy is used. Here we analyzed failure patterns, survival, and toxicity in a phase II study of patients with StageIII NSCLC treated with dose escalated proton therapy and concurrent chemotherapy.
Materials/Methods: Patients with Stage III NSCLC were to be given proton therapy to 74 cobalt-Gray equivalents (CGE) con-current with weekly carboplatin and paclitaxel. Most patients were not considered candidates for conventional-dose (60-Gy) pho-ton therapy because of bulky primary tumors or multiple stations of mediastinal nodes or contralateral mediastinal/hilar orsupraclavicular node involvement. All patients underwent staging with PET/CT and treatment simulation with 4-dimensional(4D) CT; internal gross tumor volumes (IGTV) were delineated using maximal intensity projection (MIP) and modified by visualverification of the target volume throughout 10 breathing phases. Elective lymph nodes were not irradiated intentionally. IGTVwith MIP density was used to design compensators and apertures to account for tumor motion. Passively scattered protonswere delivered in 3-field arrangements. All patients underwent 4D CT resimulation during treatment to determine whether adaptedreplanning was needed. Follow-up care comprised CT imaging and clinical examination every 3 months after treatment for 2 yearsplus PET imaging at 3–5 months and annually thereafter. Recurrence was defined as evidence of persistent or progressive diseaseon avid PET or biopsy.
Results: Of 42 enrolled patients, findings for the 30 with at least 7 months’ follow-up are reported here. At a median follow-up timeof 16 months (range, 7–26 months), no patients had experienced Grade 4 or 5 toxicity. The most common non-hematologic Grade 3adverse effect was dermatitis (13.3%) followed by esophagitis (6.7%) and pneumonitis (3.3%). Rates of isolated local failure in theplanned target volume (PTV) and in regional lymph nodes outside the PTV (elective nodal region) were both 13.3%; rate of distantmetastasis was 20%; and rate of distant metastasis + local/regional failure was 16.7%. Median overall survival has not been reachedwith current follow-up.
Conclusions: Dose-escalated concurrent proton therapy and chemotherapy seems to improve local control with less toxicity thanphoton therapy. Longer follow-up is needed.
Author Disclosure: J.Y. Chang, None; R. Komaki, None; M.K. Bucci, None; C. Lu, None; H.Y. Wen, None; B. DeGracia, None;M. Gillin, None; R. Mohan, None; J.D. Cox, None.
2591 Local Failure after Complete Resection of ‘‘Early-Stage’’ Non–small Cell Lung Cancer: The Potential Role
of Postoperative Radiation TherapyM. Saynak1,2, N. K. Veeramachaneni2, J. L. Hubbs2, J. Nam2, L. B. Marks2
1Trakya University Hospital, Edirne, Turkey, 2University of North Carolina, Chapel Hill, NC
Purpose/Objective(s): Surgery is the standard treatment for early stage non–small cell lung cancer (NSCLC). ‘‘Conventional wis-dom’’ is that the rate of local/regional failure (LRF) is low, and that adjuvant postoperative RT is not necessary. We herein quantifythe risk of local/regional failure in a large series of resected patients at tertiary referral center.
Materials/Methods: The records of 270 patients undergoing complete resection (lobectomy, or pneumonectomy) for pathologicalT1–3 N0–1 (UICC 7th edition staging) NSCLC from 1996–2006 were reviewed. (N2 disease, benign diagnosis, or carcinoid tu-mors were excluded). Median age 66 years. Pathology: Adeno 43%, squamous 43%, other 14%. Adjuvant chemotherapy was givenin 11%, but no patient received postoperative RT. Crude and actuarial (Kaplan-Meier) rates of LRF, as the first site of failure, werecomputed. LRF was considered as the lung, surgical stump, or hilar, mediastinal or supraclavicular nodes. Follow-up duration inthe patients without an event was 1–148 (median 39) months; 232 patients had $ 6 months of follow-up. The numbers of evaluablesurviving patients at $1, $3, and $5 years postresection are 130, 88, and 55, respectively.
Results: For the overall group, the crude rate of LRF was 26%; 14% as the sole site of failure, and 12% with concurrent local/re-gional and distant recurrence. The crude rates of the LRF by pathologic stage are T1N0 20% (n = 94), T1N1 25% (n = 17), T2N019% (n = 83), T2N1 33% (n = 24), T3N0 31% (n = 32), T3N1 50% (n = 12), T4N0 67% (n = 6), T4N1 0% (n = 2). For the overallgroup, the actuarial 5 year LRF rate was 37%. The actuarial 5 years rates of LRF by stage are: T1N0 30%, T1N1 42%, T2N0 31%,T2N1 53%, T3N0 46%, T3N1 100%, T4N0 77%, T4N1 0%. The rate of failure at the different sites was lung (10%), stump (4.8%),hilum (5.2%), mediastinum (12.6%), supraclavicular (1.5%), and chest wall (2.6%); several patients who failed in multiple local/regional sites are counted more than once.
Conclusions: LRF rates (by both crude and actuarial measures) are high ($ 20–30%) following gross total resection of early stageNSCLC. The role of postoperative RT in these patients should be reassessed.
Author Disclosure: M. Saynak, None; N.K. Veeramachaneni, None; J.L. Hubbs, None; J. Nam, None; L.B. Marks, None.
2592 The Effect of Bioequivalent Radiation Dose with Treatment Time on Survival of Limited-stage Small–cell
Lung CancerB. Xia, X. L. Fu, X. W. Cai, J. D. Zhao, G. Y. Chen, M. Fan, H. J. Yang, K. L. Zhao
Fudan University Cancer Hospital, Shanghai, China
Purpose/Objective(s): This study aimed to investigate the effect of bioequivalent radiation dose with treatment time on overallsurvival in patients with limited-stage small–cell lung cancer (LS-SCLC).
Materials/Methods: LS-SCLC patients treated with radical radiotherapy(. or =50 Gy) and sequential chemotherapy (EP scheme)between January 2000 and June 2006 were analyzed retrospectively. Bioequivalent radiation dose that contained the factor of treat-ment time (BED-T) was calculated to compare the radiation response because of various fractionated radiotherapy regimens. Thesurvival curves were constructed by the Kaplan-Meier method and compared by the log–rank test. The relative significance of thevariables in the predictive factors of overall survival was assessed by multivariate Cox proportional hazards regression analysis.
Results: A total of one hundred and fifty-one patients were entered (121 men and 30 women), the median age was 62 years (range,35 to 83 years). Radiation dose ranged from 50 to 70.2 Gy (median 56 Gy) given over 24–66 days, corresponding to a BED-T of25.12 to 59.19 Gy10 (median 41.2 Gy10). The median survival of the entire cohort was 22.3 months, and 2- and 5-year survival rateswere 43% and 23%, respectively. Patients with a BED-T . or = 39.66 Gy10 (equivalent to 60 Gy in 30 fractions in 6 weeks) have
