- Email: [email protected]
Acute Toxicities and Clinical Outcomes of Intensity Modulated Proton Therapy for Non-Small Cell Lung Cancer
Volume 96 Number 2S Supplement 2016 Author Disclosure: Z. Hui: None. Y. Men: None. J. Liang: None. X. Wang: None. J. Lv: None. Z. Zhou: None. Q. Feng: None. Z. Xiao: None. D. Chen: None. H. Zhang: None. W. Yin: None. L. Wang: None.
3061 Impact of Pretreatment Interstitial Lung Disease on Radiation Pneumonitis and Survival in Patients Treated With Lung Stereotactic Body Radiation Therapy (SBRT) D. Glick,1,2 S. Lyen,3 L. Le,1 P.E. Lindsay,2,4 O. Wong,1 A. Bezjak,2,5 A.M. Brade,2,5 J. Cho,1,2 A.J. Hope,1,2 A. Sun,1,2 S. Shapera,3 S. Kandel,3 and M.E. Giuliani1,2; 1Princess Margaret Cancer Centre, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada, 3University Health Network, Toronto, ON, Canada, 4Department of Radiation Physics, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada, 5Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada Purpose/Objective(s): To determine the impact of pre-treatment interstitial lung disease (ILD) on radiation pneumonitis and overall survival (OS) in patients treated with lung SBRT. Materials/Methods: Patients treated with lung SBRT between October 2004 and July 2015 at our institution were included. Pre-treatment CT scans were reviewed by experienced thoracic radiologists and interstitial changes were classified according to American Thoracic Society guidelines. Ground glass opacities (GGO), reticulations and honeycombing were scored and involvement to the nearest 5% was used to calculate Washko and Kazerooni scores. Radiation pneumonitis (RP) was prospectively documented using the CTCAE V4.0 criteria. Pre-treatment imaging characteristics, lung and heart dose parameters and clinical variables including smoking status and pulmonary function were assessed by univariate (UVA) and multivariate analysis (MVA). OS was assessed by log rank test and impact of ILD on overall survival was assessed by Cox regression. Results: 542 patients were assessed with 56 having evidence of interstitial changes on pretreatment scans. These included 12 cases of usual interstitial pneumonia (UIP), 27 cases of possible UIP and 17 cases of age related reticulations thought to be unrelated to ILD. RP was significantly higher in the 39 patients with ILD (grade 2 20.5% vs 5.8%, P<0.01; grade 3 10.3% vs 1.0%, P<0.01). Of the 3 cases of grade 5 RP observed in our series, 2 had imaging features of ILD. On UVA, radiographic evidence of ILD, Washko score, lung parameters (V5/V10/V15/V20/mean lung dose) and performance status were significant predictors of grade 2 RP. Age related reticulations were not associated with increased toxicity. On MVA, ILD (OR 5.18, P<0.01) and mean lung dose (OR 1.003, P<0.01) were predictors of RP. ILD did not significantly affect OS on UVA or MVA. Median survival was 26.5 months in the ILD cohort and 36.6 in the ILD negative cohort (P Z 0.09). Conclusion: Radiographic evidence of ILD is a significant risk factor for RP in patients treated with lung SBRT, but did not impact OS. CT scans should be reviewed for evidence of ILD prior to SBRT and involvement of respirology for management is essential. If ILD patients are treated with SBRT, they should be monitored closely for RP. Author Disclosure: D. Glick: None. S. Lyen: None. L. Le: None. P.E. Lindsay: None. O. Wong: None. A. Bezjak: None. A.M. Brade: None. J. Cho: None. A.J. Hope: Travel Expenses; Elekta Inc. A. Sun: None. S. Shapera: None. S. Kandel: None. M.E. Giuliani: Travel Expenses; Elekta Inc.
3062 Stereotactic Ablative Body Radiation Therapy (SABR) for Primary Non-Small Cell Lung Cancer: Achieving Local Control With a Lower Biologically Effective Dose (BED) S. Zhu,1 J. Lightsey,1 B.S. Hoppe,2 P. Okunieff,1 P. Gopalan,3 F.J. Kaye,3 C.G. Morris,2 and A.R. Yeung1; 1Department of Radiation Oncology, University of Florida, Gainesville, FL, 2Department of Radiation Oncology, University of Florida, Jacksonville, FL, 3Department of Medicine, University of Florida, Gainesville, FL
Poster Viewing E431 Purpose/Objective(s): The optimal fractionation schedule and BED for SABR for non-small cell lung cancer (NSCLC) is controversial. We evaluated outcomes in patients with NSCLC treated with primary SABR with a relatively low BED (BED10) of either 100 Gy or 105.6 Gy. Materials/Methods: We retrospectively reviewed the medical records of all patients treated with definitive SBRT for primary NSCLC from June 2003 to November 2013 at our institution under an IRB-approved protocol. All patients were either deemed poor surgical candidates or refused surgery. Patients were treated with either 48 Gy in 4 fractions (BED10 Z 105.6 Gy) or 50 Gy in 5 fractions (BED10 Z 100 Gy). The KaplaneMeier product-limit method was used to calculate the rates of overall survival (OS), cause-specific survival (CSS), disease-free survival (DFS), local control, local-lobar control, local-lobar-nodal control, and freedom from distant metastases. A lobar failure was defined as a recurrence in the same lobe, but a different location, as the treated tumor. Local versus lobar failure was determined by reviewing the imaging used to determine recurrence, and comparing the location of the recurrent lesion to the original pretreatment lesion. Toxicities were graded with Common Terminology Criteria for Adverse Events, version 4.0. Results: Ninety-four patients met the inclusion criteria. Median follow-up duration for living patients was 3.3 years (range, 2.1 to 9.4). The median age of the cohort was 69 years (range, 50-87 years), and 54 (57%) were women. Ninety-two (98%) patients were previous or current smokers. Seventy-eight (83%) had chronic obstructive pulmonary disease. Median tumor size was 2.0 cm (range, 0.7-4.3 cm); 50% had stage T1a disease and 37% had T1b. Forty-five patients (48%) had biopsy-proven tumors. Unbiopsied lesions had at least one prior comparison scan to show serial growth over time. Patients were treated with one of two fractionation schedules: 34 (36%) received 4 fractions of 12 Gy (BED10 105.6 Gy) and 60 (64%) received 5 fractions of 10Gy (BED10 100 Gy). At 3 years, rates for OS, CSS, DFS, local control, local-lobar control, and local-lobar-nodal control were 42%, 68%, 63%, 92%, 84%, and 82%, respectively. At 3 years, 21% of patients developed distant metastases. Seven patients (7.4%) experienced grade 3 toxicities including radiation pneumonitis (n Z 2), pneumonia (n Z 2), pleural effusion (n Z 2), and esophageal stenosis (n Z 1). Conclusion: Our results show that treating early-stage NSCLC with SABR fractionation schedules with a BED10 of 100 Gy to 105.6 Gy yielded excellent local and local-regional control rates, which are comparable to those previously reported in the literature with higher BED10. Author Disclosure: S. Zhu: None. J. Lightsey: None. B.S. Hoppe: None. P. Okunieff: None. P. Gopalan: None. F.J. Kaye: None. C.G. Morris: None. A.R. Yeung: None.
3063 Acute Toxicities and Clinical Outcomes of Intensity Modulated Proton Therapy for Non-Small Cell Lung Cancer G. Green,1 F. Giap,2 R. Lepage,3 L. Dong,3 C.J. Rossi,3 J.J. Urbanic,1 and H. Giap3; 1University of California, San Diego, La Jolla, CA, 2 University of Texas Southwestern, Dallas, TX, 3Scripps Proton Therapy Center, San Diego, CA Purpose/Objective(s): Intensity modulated proton therapy (IMPT) has been used exclusively at our institution to treat lung cancer patients over the past 2 years as opposed to other centers which predominantly use passive scattering proton radiation. IMPT may better spare critical organs at risk compared to intensity modulated photon radiation therapy (IMRT), or passive scattering proton therapy. This may allow dose escalation while minimizing toxicities; however, range uncertainties associated with IMPT complicate its use, particularly with moving targets within the lung. The primary endpoint of our study was to investigate acute toxicity associated with IMPT. Secondary endpoints were local control, local-regional failure, recurrence free survival, and overall survival. Materials/Methods: We identified 20 patients between 2014 and 2015, stage I-II (n Z 6) III (n Z 14), with NSCLC. Median follow up was 4.1 months (range 2-9 months). Radiation dose and guideline was prescribed using guidelines of RTOG 1308 for stage III patients and 67.5Gy in 15 fractions for stage I. Patients, immobilized with a custom cushion, were set
E432
International Journal of Radiation Oncology Biology Physics
up in the supine position with arms over their head. All patients underwent 4-D CT simulation for treatment planning. If movement was less than 1 cm, then the ITV technique was used. If the tumor motion was more than 1 cm, then motion management was done using the DIBH SDX system. Image guidance was done with daily OBI using orthogonal kv-kV x-rays prior to treatment. Treatment was delivered with 2 beams using IMPT with Single Field Optimization technique. Weekly adaptive simulation was done with CT. Acute toxicity was graded according to CTCAE 4.0. Results: There were no grade 3 or greater acute esophageal or pulmonary toxicities. Two patients (10%) had grade 2 acute esophagitis. There were no grade 4-5 toxicities. The crude rate of local-regional failure at 1 year was 86% for both the stage I and stage III patients. Overall survival at 1 year was 86% for the stage III patients and 100% for the early stage patients. Predictive factors for clinical outcomes were analyzed. Conclusion: IMPT is feasible, and it is a safe and effective modality to treat both early and locally advanced lung cancer. Our preliminary data suggest that IMPT had low acute toxicity and local failure rate compared to historical data. Further validation in prospective randomized trials are currently underway to confirm efficacy and safety as compared to other treatment modalities. Author Disclosure: G. Green: None. F. Giap: None. R. Lepage: None. L. Dong: None. C.J. Rossi: None. J.J. Urbanic: None. H. Giap: None.
formate were detected in 75% and 50% of the cancer group and 43% and 57% of the control group, with higher median concentration of the metabolites in cancer group. Methanol was detected in 75% and 100% of the cancer and control group respectively, with median lower concentration of the metabolite in the cancer group (P Z 0.040). Subsequently EBC samples were also analyzed by an LC-QTOF-Mass Spectroscopy (MS) using a non-targeted approach. A total of 625 compounds were detected in all EBC samples combined among which, 4 were up regulated in patients with lung cancer (T-Test, P<0.05) Conclusion: Lower concentrations of methanol (EBC), glycoprotein (sputum), absence of glucose in sputum identified through MRS and up regulation of 4 specific metabolites in EBC identified through MS in patients with known lung cancer suggest that MRS and MS may provide a lung cancer specific metabolic profile that can be used to develop a noninvasive tool to screen for lung cancer in high risk population. Author Disclosure: N. Ahmed: None. T. Bezabeh: None. O. Ijare: None. R. Myers: None. R.K. Alomran: None. S. Banerji: None. Z. Nugent: None. Z. Bshouty: None.
3064 Proton Magnetic Resonance Spectroscopy (1H MRS) of Sputum and Exhaled Breath Condensate: A Noninvasive Tool for Lung Cancer Screening N. Ahmed,1 T. Bezabeh,2 O.B. Ijare,2 R. Myers,3 R.K. Alomran,4 S. Banerji,5 Z. Nugent,6 and Z. Bshouty7; 1CancerCare Manitoba, Winnipeg, MB, Canada, 2University of Winnipeg, Winnipeg, MB, Canada, 3 Health Sciences Centre, University of Manitoba, Winnipeg, MB, Canada, 4 University of Manitoba, Winnipeg, MB, Canada, 5CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada, 6Department of Epidemiology and Cancer Registry, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada, 7Health Sciences Centre, University of Manitoba, Winnipeg, MB, Canada Purpose/Objective(s): Lung cancer is the leading cause of cancer-specific mortality in North America with over 158,000 estimated deaths in the USA and 20,000 deaths in Canada. Main reason for the high mortality is the advanced stage at diagnosis in the majority of patients. Early detection of lung cancer by screening high-risk individuals has been proposed to improve survival. An effective screening program may prevent up to 80% of the deaths from lung cancer. We undertook this study to determine if 1H Magnetic Resonance Spectroscopy (MRS) of sputum and exhaled breath condensate samples can complement and or provide an alternate tool to screen and detect lung cancer among high-risk population. Materials/Methods: Sputum and exhaled breath condensate (EBC) samples were collected from 15 patients. Pathologically confirmed non-small cell lung cancer (NSCLC, n Z 8), and patients with respiratory conditions other than lung cancer (controls, n Z 7) were enrolled. Both sputum and EBC samples were collected in thirteen patients; two patients provided EBC samples only. Sputum samples were thawed and 250 mL of each sample was dispersed in 2M NaCl (prepared in PBS buffer) solution in the ratio 1:1 (v/v) and vortexed to get homogenous clear suspension; frozen EBC samples were thawed and 500 mL neat sample was transferred into the NMR tube (with a reusable co-axial capillary tube containing standard TSP solution in D2O) for analysis. All MRS experiments were performed on a Bruker Avance 400 MHz NMR spectrometer at our university. In order to detect metabolite signals, the water signals in both EBC and sputum samples were suppressed using PRESAT or excitation sculpting (ES) pulse sequence. The MRS lab staff was blind to the diagnoses until all the samples were analyzed. Results: In EBC samples, propionate was detected in 43% of the patients in both groups; with similar median concentration of the metabolite. Ethanol and acetate were detected in all patients, with relatively higher median concentration of the metabolites in the cancer group. Acetone and
3065 Tumor Regression Curve During and After Concurrent Chemotherapy and Proton Therapy for Unresectable Stage III NonSmall Cell Lung Cancer: Comparison With Chemo-X-Radiation Therapy H. Iwata,1,2 H. Ogino,1 K. Akita,3 N. Takama,4 T. Murai,2 K. Uchiyama,5 K. Nakamae,6 M. Iwana,7 F. Baba,7 Y. Shibamoto,2 and J.E. Mizoe1; 1 Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan, 2Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Department of Respiratory Medicine, Nagoya City West Medical Center, Nagoya, Japan, 4Department of Radiology, Nagoya Medical Center, Nagoya, Japan, 5Department of Radiology, Nagoya Daini Red Cross Hospital, Nagoya, Japan, 6Department of Thoracic Surgery, Nagoya City West Medical Center, Nagoya, Japan, 7Department of Radiation Therapy, Nagoya City West Medical Center, Nagoya, Japan Purpose/Objective(s): Since proton therapy provides a more focused dose distribution on the tumor compared with X-ray therapy, dose escalation is feasible, and it is expected to improve the therapeutic ratio. The relative biological effectiveness of proton therapy has been reported to be about 1.1, but many biological aspects, including anti-tumor effects when combined with concomitant chemotherapy, remain unclear. In this study, we evaluated the tumor regression curves during and after concurrent chemotherapy and proton therapy (CCPT) for unresectable stage III non-small cell lung cancer (NSCLC), and compared them with those obtained using X-rays. Materials/Methods: A clinical study was conducted involving patients with unresectable stage III NSCLC. Two courses of 4-week-cycle chemotherapy with CDDP 60 mg/m2 on day 1 and S-1 80 mg/m2/day for 14 consecutive days were performed with concurrent proton therapy with 70 GyE in 35 fractions. About 10, 20, and 30 days after the beginning and on the last day of proton therapy, verification CT simulation was carried out under the same conditions as performed at the initial treatment planning, and the gross tumor volume (GTV) of the primary lesion was compared with that before irradiation using a radiation therapy planning support tool. Then, we compared the changes of GTV in the series of concurrent chemotherapy and X-rays (CCRT) using 60-66 Gy and the same or another (2 courses of 4-week-cycle chemotherapy with CDDP 80 mg/m2 on day 1 and vinorelbine 20 mg/m2 on days 1 and 8) regimen of chemotherapy. In the CCRT series, verification CT was carried out at the beginning and about 30 days later. Results: A total of 25, 20 and 20 patients were registered and treated using CCPT, CCRT using the same regimen and CCRT with CDDP and vinorelbine, respectively. The median GTV at about 10, 20, and 30 days after the beginning and on the last day of proton therapy compared with that before treatment was 73.1% (range, 24.4-93.7), 54.1% (2.2-87.8), 44.8% (0-75.0), and 28.3% (0-65.3), respectively. Although squamous cell carcinomas regressed relatively quickly, the volume decreased to half or less of the
3061 Impact of Pretreatment Interstitial Lung Disease on Radiation Pneumonitis and Survival in Patients Treated With Lung Stereotactic Body Radiation Therapy (SBRT) D. Glick,1,2 S. Lyen,3 L. Le,1 P.E. Lindsay,2,4 O. Wong,1 A. Bezjak,2,5 A.M. Brade,2,5 J. Cho,1,2 A.J. Hope,1,2 A. Sun,1,2 S. Shapera,3 S. Kandel,3 and M.E. Giuliani1,2; 1Princess Margaret Cancer Centre, Toronto, ON, Canada, 2University of Toronto, Toronto, ON, Canada, 3University Health Network, Toronto, ON, Canada, 4Department of Radiation Physics, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada, 5Department of Radiation Oncology, Princess Margaret Cancer Centre/University of Toronto, Toronto, ON, Canada Purpose/Objective(s): To determine the impact of pre-treatment interstitial lung disease (ILD) on radiation pneumonitis and overall survival (OS) in patients treated with lung SBRT. Materials/Methods: Patients treated with lung SBRT between October 2004 and July 2015 at our institution were included. Pre-treatment CT scans were reviewed by experienced thoracic radiologists and interstitial changes were classified according to American Thoracic Society guidelines. Ground glass opacities (GGO), reticulations and honeycombing were scored and involvement to the nearest 5% was used to calculate Washko and Kazerooni scores. Radiation pneumonitis (RP) was prospectively documented using the CTCAE V4.0 criteria. Pre-treatment imaging characteristics, lung and heart dose parameters and clinical variables including smoking status and pulmonary function were assessed by univariate (UVA) and multivariate analysis (MVA). OS was assessed by log rank test and impact of ILD on overall survival was assessed by Cox regression. Results: 542 patients were assessed with 56 having evidence of interstitial changes on pretreatment scans. These included 12 cases of usual interstitial pneumonia (UIP), 27 cases of possible UIP and 17 cases of age related reticulations thought to be unrelated to ILD. RP was significantly higher in the 39 patients with ILD (grade 2 20.5% vs 5.8%, P<0.01; grade 3 10.3% vs 1.0%, P<0.01). Of the 3 cases of grade 5 RP observed in our series, 2 had imaging features of ILD. On UVA, radiographic evidence of ILD, Washko score, lung parameters (V5/V10/V15/V20/mean lung dose) and performance status were significant predictors of grade 2 RP. Age related reticulations were not associated with increased toxicity. On MVA, ILD (OR 5.18, P<0.01) and mean lung dose (OR 1.003, P<0.01) were predictors of RP. ILD did not significantly affect OS on UVA or MVA. Median survival was 26.5 months in the ILD cohort and 36.6 in the ILD negative cohort (P Z 0.09). Conclusion: Radiographic evidence of ILD is a significant risk factor for RP in patients treated with lung SBRT, but did not impact OS. CT scans should be reviewed for evidence of ILD prior to SBRT and involvement of respirology for management is essential. If ILD patients are treated with SBRT, they should be monitored closely for RP. Author Disclosure: D. Glick: None. S. Lyen: None. L. Le: None. P.E. Lindsay: None. O. Wong: None. A. Bezjak: None. A.M. Brade: None. J. Cho: None. A.J. Hope: Travel Expenses; Elekta Inc. A. Sun: None. S. Shapera: None. S. Kandel: None. M.E. Giuliani: Travel Expenses; Elekta Inc.
3062 Stereotactic Ablative Body Radiation Therapy (SABR) for Primary Non-Small Cell Lung Cancer: Achieving Local Control With a Lower Biologically Effective Dose (BED) S. Zhu,1 J. Lightsey,1 B.S. Hoppe,2 P. Okunieff,1 P. Gopalan,3 F.J. Kaye,3 C.G. Morris,2 and A.R. Yeung1; 1Department of Radiation Oncology, University of Florida, Gainesville, FL, 2Department of Radiation Oncology, University of Florida, Jacksonville, FL, 3Department of Medicine, University of Florida, Gainesville, FL
Poster Viewing E431 Purpose/Objective(s): The optimal fractionation schedule and BED for SABR for non-small cell lung cancer (NSCLC) is controversial. We evaluated outcomes in patients with NSCLC treated with primary SABR with a relatively low BED (BED10) of either 100 Gy or 105.6 Gy. Materials/Methods: We retrospectively reviewed the medical records of all patients treated with definitive SBRT for primary NSCLC from June 2003 to November 2013 at our institution under an IRB-approved protocol. All patients were either deemed poor surgical candidates or refused surgery. Patients were treated with either 48 Gy in 4 fractions (BED10 Z 105.6 Gy) or 50 Gy in 5 fractions (BED10 Z 100 Gy). The KaplaneMeier product-limit method was used to calculate the rates of overall survival (OS), cause-specific survival (CSS), disease-free survival (DFS), local control, local-lobar control, local-lobar-nodal control, and freedom from distant metastases. A lobar failure was defined as a recurrence in the same lobe, but a different location, as the treated tumor. Local versus lobar failure was determined by reviewing the imaging used to determine recurrence, and comparing the location of the recurrent lesion to the original pretreatment lesion. Toxicities were graded with Common Terminology Criteria for Adverse Events, version 4.0. Results: Ninety-four patients met the inclusion criteria. Median follow-up duration for living patients was 3.3 years (range, 2.1 to 9.4). The median age of the cohort was 69 years (range, 50-87 years), and 54 (57%) were women. Ninety-two (98%) patients were previous or current smokers. Seventy-eight (83%) had chronic obstructive pulmonary disease. Median tumor size was 2.0 cm (range, 0.7-4.3 cm); 50% had stage T1a disease and 37% had T1b. Forty-five patients (48%) had biopsy-proven tumors. Unbiopsied lesions had at least one prior comparison scan to show serial growth over time. Patients were treated with one of two fractionation schedules: 34 (36%) received 4 fractions of 12 Gy (BED10 105.6 Gy) and 60 (64%) received 5 fractions of 10Gy (BED10 100 Gy). At 3 years, rates for OS, CSS, DFS, local control, local-lobar control, and local-lobar-nodal control were 42%, 68%, 63%, 92%, 84%, and 82%, respectively. At 3 years, 21% of patients developed distant metastases. Seven patients (7.4%) experienced grade 3 toxicities including radiation pneumonitis (n Z 2), pneumonia (n Z 2), pleural effusion (n Z 2), and esophageal stenosis (n Z 1). Conclusion: Our results show that treating early-stage NSCLC with SABR fractionation schedules with a BED10 of 100 Gy to 105.6 Gy yielded excellent local and local-regional control rates, which are comparable to those previously reported in the literature with higher BED10. Author Disclosure: S. Zhu: None. J. Lightsey: None. B.S. Hoppe: None. P. Okunieff: None. P. Gopalan: None. F.J. Kaye: None. C.G. Morris: None. A.R. Yeung: None.
3063 Acute Toxicities and Clinical Outcomes of Intensity Modulated Proton Therapy for Non-Small Cell Lung Cancer G. Green,1 F. Giap,2 R. Lepage,3 L. Dong,3 C.J. Rossi,3 J.J. Urbanic,1 and H. Giap3; 1University of California, San Diego, La Jolla, CA, 2 University of Texas Southwestern, Dallas, TX, 3Scripps Proton Therapy Center, San Diego, CA Purpose/Objective(s): Intensity modulated proton therapy (IMPT) has been used exclusively at our institution to treat lung cancer patients over the past 2 years as opposed to other centers which predominantly use passive scattering proton radiation. IMPT may better spare critical organs at risk compared to intensity modulated photon radiation therapy (IMRT), or passive scattering proton therapy. This may allow dose escalation while minimizing toxicities; however, range uncertainties associated with IMPT complicate its use, particularly with moving targets within the lung. The primary endpoint of our study was to investigate acute toxicity associated with IMPT. Secondary endpoints were local control, local-regional failure, recurrence free survival, and overall survival. Materials/Methods: We identified 20 patients between 2014 and 2015, stage I-II (n Z 6) III (n Z 14), with NSCLC. Median follow up was 4.1 months (range 2-9 months). Radiation dose and guideline was prescribed using guidelines of RTOG 1308 for stage III patients and 67.5Gy in 15 fractions for stage I. Patients, immobilized with a custom cushion, were set
E432
International Journal of Radiation Oncology Biology Physics
up in the supine position with arms over their head. All patients underwent 4-D CT simulation for treatment planning. If movement was less than 1 cm, then the ITV technique was used. If the tumor motion was more than 1 cm, then motion management was done using the DIBH SDX system. Image guidance was done with daily OBI using orthogonal kv-kV x-rays prior to treatment. Treatment was delivered with 2 beams using IMPT with Single Field Optimization technique. Weekly adaptive simulation was done with CT. Acute toxicity was graded according to CTCAE 4.0. Results: There were no grade 3 or greater acute esophageal or pulmonary toxicities. Two patients (10%) had grade 2 acute esophagitis. There were no grade 4-5 toxicities. The crude rate of local-regional failure at 1 year was 86% for both the stage I and stage III patients. Overall survival at 1 year was 86% for the stage III patients and 100% for the early stage patients. Predictive factors for clinical outcomes were analyzed. Conclusion: IMPT is feasible, and it is a safe and effective modality to treat both early and locally advanced lung cancer. Our preliminary data suggest that IMPT had low acute toxicity and local failure rate compared to historical data. Further validation in prospective randomized trials are currently underway to confirm efficacy and safety as compared to other treatment modalities. Author Disclosure: G. Green: None. F. Giap: None. R. Lepage: None. L. Dong: None. C.J. Rossi: None. J.J. Urbanic: None. H. Giap: None.
formate were detected in 75% and 50% of the cancer group and 43% and 57% of the control group, with higher median concentration of the metabolites in cancer group. Methanol was detected in 75% and 100% of the cancer and control group respectively, with median lower concentration of the metabolite in the cancer group (P Z 0.040). Subsequently EBC samples were also analyzed by an LC-QTOF-Mass Spectroscopy (MS) using a non-targeted approach. A total of 625 compounds were detected in all EBC samples combined among which, 4 were up regulated in patients with lung cancer (T-Test, P<0.05) Conclusion: Lower concentrations of methanol (EBC), glycoprotein (sputum), absence of glucose in sputum identified through MRS and up regulation of 4 specific metabolites in EBC identified through MS in patients with known lung cancer suggest that MRS and MS may provide a lung cancer specific metabolic profile that can be used to develop a noninvasive tool to screen for lung cancer in high risk population. Author Disclosure: N. Ahmed: None. T. Bezabeh: None. O. Ijare: None. R. Myers: None. R.K. Alomran: None. S. Banerji: None. Z. Nugent: None. Z. Bshouty: None.
3064 Proton Magnetic Resonance Spectroscopy (1H MRS) of Sputum and Exhaled Breath Condensate: A Noninvasive Tool for Lung Cancer Screening N. Ahmed,1 T. Bezabeh,2 O.B. Ijare,2 R. Myers,3 R.K. Alomran,4 S. Banerji,5 Z. Nugent,6 and Z. Bshouty7; 1CancerCare Manitoba, Winnipeg, MB, Canada, 2University of Winnipeg, Winnipeg, MB, Canada, 3 Health Sciences Centre, University of Manitoba, Winnipeg, MB, Canada, 4 University of Manitoba, Winnipeg, MB, Canada, 5CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada, 6Department of Epidemiology and Cancer Registry, CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada, 7Health Sciences Centre, University of Manitoba, Winnipeg, MB, Canada Purpose/Objective(s): Lung cancer is the leading cause of cancer-specific mortality in North America with over 158,000 estimated deaths in the USA and 20,000 deaths in Canada. Main reason for the high mortality is the advanced stage at diagnosis in the majority of patients. Early detection of lung cancer by screening high-risk individuals has been proposed to improve survival. An effective screening program may prevent up to 80% of the deaths from lung cancer. We undertook this study to determine if 1H Magnetic Resonance Spectroscopy (MRS) of sputum and exhaled breath condensate samples can complement and or provide an alternate tool to screen and detect lung cancer among high-risk population. Materials/Methods: Sputum and exhaled breath condensate (EBC) samples were collected from 15 patients. Pathologically confirmed non-small cell lung cancer (NSCLC, n Z 8), and patients with respiratory conditions other than lung cancer (controls, n Z 7) were enrolled. Both sputum and EBC samples were collected in thirteen patients; two patients provided EBC samples only. Sputum samples were thawed and 250 mL of each sample was dispersed in 2M NaCl (prepared in PBS buffer) solution in the ratio 1:1 (v/v) and vortexed to get homogenous clear suspension; frozen EBC samples were thawed and 500 mL neat sample was transferred into the NMR tube (with a reusable co-axial capillary tube containing standard TSP solution in D2O) for analysis. All MRS experiments were performed on a Bruker Avance 400 MHz NMR spectrometer at our university. In order to detect metabolite signals, the water signals in both EBC and sputum samples were suppressed using PRESAT or excitation sculpting (ES) pulse sequence. The MRS lab staff was blind to the diagnoses until all the samples were analyzed. Results: In EBC samples, propionate was detected in 43% of the patients in both groups; with similar median concentration of the metabolite. Ethanol and acetate were detected in all patients, with relatively higher median concentration of the metabolites in the cancer group. Acetone and
3065 Tumor Regression Curve During and After Concurrent Chemotherapy and Proton Therapy for Unresectable Stage III NonSmall Cell Lung Cancer: Comparison With Chemo-X-Radiation Therapy H. Iwata,1,2 H. Ogino,1 K. Akita,3 N. Takama,4 T. Murai,2 K. Uchiyama,5 K. Nakamae,6 M. Iwana,7 F. Baba,7 Y. Shibamoto,2 and J.E. Mizoe1; 1 Department of Radiation Oncology, Nagoya Proton Therapy Center, Nagoya City West Medical Center, Nagoya, Japan, 2Department of Radiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, 3Department of Respiratory Medicine, Nagoya City West Medical Center, Nagoya, Japan, 4Department of Radiology, Nagoya Medical Center, Nagoya, Japan, 5Department of Radiology, Nagoya Daini Red Cross Hospital, Nagoya, Japan, 6Department of Thoracic Surgery, Nagoya City West Medical Center, Nagoya, Japan, 7Department of Radiation Therapy, Nagoya City West Medical Center, Nagoya, Japan Purpose/Objective(s): Since proton therapy provides a more focused dose distribution on the tumor compared with X-ray therapy, dose escalation is feasible, and it is expected to improve the therapeutic ratio. The relative biological effectiveness of proton therapy has been reported to be about 1.1, but many biological aspects, including anti-tumor effects when combined with concomitant chemotherapy, remain unclear. In this study, we evaluated the tumor regression curves during and after concurrent chemotherapy and proton therapy (CCPT) for unresectable stage III non-small cell lung cancer (NSCLC), and compared them with those obtained using X-rays. Materials/Methods: A clinical study was conducted involving patients with unresectable stage III NSCLC. Two courses of 4-week-cycle chemotherapy with CDDP 60 mg/m2 on day 1 and S-1 80 mg/m2/day for 14 consecutive days were performed with concurrent proton therapy with 70 GyE in 35 fractions. About 10, 20, and 30 days after the beginning and on the last day of proton therapy, verification CT simulation was carried out under the same conditions as performed at the initial treatment planning, and the gross tumor volume (GTV) of the primary lesion was compared with that before irradiation using a radiation therapy planning support tool. Then, we compared the changes of GTV in the series of concurrent chemotherapy and X-rays (CCRT) using 60-66 Gy and the same or another (2 courses of 4-week-cycle chemotherapy with CDDP 80 mg/m2 on day 1 and vinorelbine 20 mg/m2 on days 1 and 8) regimen of chemotherapy. In the CCRT series, verification CT was carried out at the beginning and about 30 days later. Results: A total of 25, 20 and 20 patients were registered and treated using CCPT, CCRT using the same regimen and CCRT with CDDP and vinorelbine, respectively. The median GTV at about 10, 20, and 30 days after the beginning and on the last day of proton therapy compared with that before treatment was 73.1% (range, 24.4-93.7), 54.1% (2.2-87.8), 44.8% (0-75.0), and 28.3% (0-65.3), respectively. Although squamous cell carcinomas regressed relatively quickly, the volume decreased to half or less of the