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Cone Beam Computed Tomography in Lung Stereotactic Ablative Radiation Therapy: Predictive Parameters of Early Response
E462
International Journal of Radiation Oncology Biology Physics
Patient population was divided into 2 subgroups by optimal cut off values of PTV, GTV (ml), mean lung dose (Gy), ipsilateral and bilateral V5, V10, V15, V20, V25, V30, V35, and V40 (%). Selected cut off values are calculated according to ROC curve analysis. Selected cut off values of each variables are obtained from the receiver operating characteristic (ROC) curves. Results: At the median follow-up time of 9 months (range, 3-31), symptomatic RP was observed in 12 patients (20.3%). PTV of less than 14.36 cc showed significantly lower symptomatic RP rate compared to larger PTV group (8.6% vs 27.0%, P Z 0.042). According to the dose volume features, symptomatic RP was observed in 29.0% for the patients whose V25 is greater than 2.78%, while the rate was 9.8% for the remainder (P Z 0.035). Two patients developed grade 3 RP while none did grade 4 and 5. There was no local failure for treated sites so far. Conclusion: The incidence of symptomatic RP following our SABR protocol was acceptable with limited number of grade 3 or more. We were able to suggest statistically significant cut off values for PTV and V25 in symptomatic RP events. Despite a short follow-up time and the variation of prescribed dose, no local failure so far is encouraging. Author Disclosure: K. Kim: None. C. Lee: None. J. Cho: None.
moment. Continued follow-up is needed to obtain the long-term therapeutic and safety results and to demonstrate that AHypoFR just like this study can be safely delivered to the central type small lung tumors with appreciable anti-tumor effects. It may become possible, our simple AHypoFR can be an alternative treatment of central type small lung tumors to SBRT which is difficult to apply to those tumors because of the higher risk of complications of mediastinal organs. Author Disclosure: Y. Hatayama: None. M. Aoki: None. H. Kawaguchi: None. K. Hirose: None. M. Sato: None. H. Akimoto: None. Y. Takai: None.
3137 Preliminary Results of Accelerated Hypofractionated Radiation Therapy for Small Central Lung Tumors Y. Hatayama,1 M. Aoki,1 H. Kawaguchi,1 K. Hirose,1 M. Sato,1 H. Akimoto,1 and Y. Takai2; 1Hirosaki University, Hirosaki, Japan, 2 Southern Tohoku BNCT Research Center, Koriyama, Japan Purpose/Objective(s): To improve the local control rates and survival rates over conventional radiation therapy and to reduce adverse effect, we attempted to treat central type stage I non-small cell lung cancers and small solitary metastatic lung tumors with accelerated hypo-fractionated radiation therapy (AHypoFR) using a fraction size of 2.5-3 Gy. The purpose of the study is to evaluate preliminary efficacy and toxicity of AHypoFR. Materials/Methods: Forty patients with small central lung tumors underwent AHypoFR between November 2006 and January 2015. We used 10 MV X-rays and coplanar three fields. The number of fractions ranged between 24 and 28 with a fraction size of 2.5 3 Gy. A total dose of 7075 Gy at the isocenter of the PTV (planning target volume) was administered in each patient. No patients received chemotherapy during radiation therapy. The cumulative survival rate and local control rate were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 3 of the Common Terminology Criteria for Adverse Events. Results: The study included 27 males and 13 females with a median age of 79 years (age range, 60-87 years). The tumor size was T1a in 9 patients, T1b in 17, and T2a in 14 with a median size of 26.5cm (range, 1149cm). The histology was adenocarcinoma in 20 cases, squamous cell carcinoma in 11, other histologies in two, and clinically diagnosed in seven. The median follow-up period was 23 months. Complete response was achieved in 3 (7.5%) patients after treatment and partial response in 17 (42.5%) patients. A total of 40 patients, the 2-year and 3-year local control rates were 87.3% and 81.8%, respectively. The 2-year and 3-year overall survival rates were 78.9% and 66.7%, respectively. During the follow-up, local progression occurred in three patients (7.5%). Seven patients developed distant metastasis, 2 developed carcinomatous pleurisy, 2 developed intrapulmonary metastasis, and 2 developed lymph node metastasis. Eight patients have died so far. In 5 patients, death was a result of disease progression. One patient died of interstitial pneumonia unrelated lung irradiation and 1 patient died of cerebral hemorrhage and unknown cause in 1 patient. Three patients experienced Grade 3 pneumonitis, but no more severe adverse events (grade 3) have yet been observed in any patients. Conclusion: We have introduced AHypoFR for small central lung tumors in order to improve outcomes than conventional radiation therapy and to reduce toxicities than SBRT. Our report is one of the best results at the
3138 Cone Beam Computed Tomography in Lung Stereotactic Ablative Radiation Therapy: Predictive Parameters of Early Response F. Alongi,1 R. Mazzola,1 F. Ricchetti,1 A. Fiorentino,1 S. Fersino,1 N. Giaj Levra,1 U. Tebano,2 G. Sicignano,1 S. Naccarato,1 and R. Ruggieri1; 1 Radiation Oncology Department Sacro Cuore Hospital, Negrar-Verona, Italy, 2Radiation Oncology School, University of Padova, Padova, Italy Purpose/Objective(s): To analyze lung lesion volume variations by contouring on cone-beam computed tomography (CBCT) images to evaluate early predictive parameters of stereotactic ablative radiation therapy (SABR) treatment response. Materials/Methods: The prescribed dose of SABR varied according to the tumor site (central or peripheral) and maximum diameter of the lesions using a strategy of risk-adapted dose prescription with a range of dose between 48 and 70 Gy in 3-10 consecutive fractions. For the purpose of the analysis, gross tumor volume (GTV) was re-contoured for each patient at first and last CBCT using 2 lung levels/window: a) -600/1000 Hounsfield Units (HU), b) -1000/250 HU. Univariate analysis was performed to evaluate a correlation between lung lesions variations on CBCT using the two window levels with the treatment response 6 months after SABR. The analysis was conducted considering the following variables: number of fractions, time between initial and final fraction, BED, Pre-SABR GTV volume. Cut-points of lesion volume reduction were evaluated to determine the correlation with lung lesions complete response six months after SABR. Results: Forty-one lung lesions were evaluated. Eighty-two lung lesions were re-contoured for each CBCT levels/window. A lung lesions shrinkage of at least 20% revealed to be statistically correlated to lesions complete response six months after SABR for both the CBCT levels/windows used. The probability of complete response ranged between 6 and 8 times higher in respect to the CBCT lung level adopted comparing to patients without a GTV decrease of 20%. Conclusion: Early predictive parameters of SABR efficacy could be helpful for clinicians in order to improve patient-tailored surveillance and management. According to current findings, a lung lesion shrinkage at least of 20% at last session of SABR could be predictable for early complete response. Further investigations are needed. Author Disclosure: F. Alongi: None. R. Mazzola: None. F. Ricchetti: None. A. Fiorentino: None. S. Fersino: None. N. Giaj Levra: None. U. Tebano: None. G. Sicignano: None. S. Naccarato: None. R. Ruggieri: None.
3139 The Safety of Critical Structures Throughout Treatment for DoseEscalated Locally Advanced Non-Small Cell Lung Cancer Patients T.B. Nielsen,1 M. Nielsen,1 T. Schytte,2 C. Brink,1,3 O. Hansen,2 and R.S. Thing3; 1Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark, 2Department of Oncology, Odense University Hospital, Odense, Denmark, 3Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Purpose/Objective(s): In the ongoing multi-center trial NARLAL2 by the Danish Oncologic Lung Cancer Group, patients with locally-advanced NSCLC are randomized to standard homogeneous treatment of 66 Gy/33 fractions and inhomogeneous dose-escalated treatment in 33 fractions. The
International Journal of Radiation Oncology Biology Physics
Patient population was divided into 2 subgroups by optimal cut off values of PTV, GTV (ml), mean lung dose (Gy), ipsilateral and bilateral V5, V10, V15, V20, V25, V30, V35, and V40 (%). Selected cut off values are calculated according to ROC curve analysis. Selected cut off values of each variables are obtained from the receiver operating characteristic (ROC) curves. Results: At the median follow-up time of 9 months (range, 3-31), symptomatic RP was observed in 12 patients (20.3%). PTV of less than 14.36 cc showed significantly lower symptomatic RP rate compared to larger PTV group (8.6% vs 27.0%, P Z 0.042). According to the dose volume features, symptomatic RP was observed in 29.0% for the patients whose V25 is greater than 2.78%, while the rate was 9.8% for the remainder (P Z 0.035). Two patients developed grade 3 RP while none did grade 4 and 5. There was no local failure for treated sites so far. Conclusion: The incidence of symptomatic RP following our SABR protocol was acceptable with limited number of grade 3 or more. We were able to suggest statistically significant cut off values for PTV and V25 in symptomatic RP events. Despite a short follow-up time and the variation of prescribed dose, no local failure so far is encouraging. Author Disclosure: K. Kim: None. C. Lee: None. J. Cho: None.
moment. Continued follow-up is needed to obtain the long-term therapeutic and safety results and to demonstrate that AHypoFR just like this study can be safely delivered to the central type small lung tumors with appreciable anti-tumor effects. It may become possible, our simple AHypoFR can be an alternative treatment of central type small lung tumors to SBRT which is difficult to apply to those tumors because of the higher risk of complications of mediastinal organs. Author Disclosure: Y. Hatayama: None. M. Aoki: None. H. Kawaguchi: None. K. Hirose: None. M. Sato: None. H. Akimoto: None. Y. Takai: None.
3137 Preliminary Results of Accelerated Hypofractionated Radiation Therapy for Small Central Lung Tumors Y. Hatayama,1 M. Aoki,1 H. Kawaguchi,1 K. Hirose,1 M. Sato,1 H. Akimoto,1 and Y. Takai2; 1Hirosaki University, Hirosaki, Japan, 2 Southern Tohoku BNCT Research Center, Koriyama, Japan Purpose/Objective(s): To improve the local control rates and survival rates over conventional radiation therapy and to reduce adverse effect, we attempted to treat central type stage I non-small cell lung cancers and small solitary metastatic lung tumors with accelerated hypo-fractionated radiation therapy (AHypoFR) using a fraction size of 2.5-3 Gy. The purpose of the study is to evaluate preliminary efficacy and toxicity of AHypoFR. Materials/Methods: Forty patients with small central lung tumors underwent AHypoFR between November 2006 and January 2015. We used 10 MV X-rays and coplanar three fields. The number of fractions ranged between 24 and 28 with a fraction size of 2.5 3 Gy. A total dose of 7075 Gy at the isocenter of the PTV (planning target volume) was administered in each patient. No patients received chemotherapy during radiation therapy. The cumulative survival rate and local control rate were calculated using the Kaplan-Meier method. Treatment toxicities were evaluated using version 3 of the Common Terminology Criteria for Adverse Events. Results: The study included 27 males and 13 females with a median age of 79 years (age range, 60-87 years). The tumor size was T1a in 9 patients, T1b in 17, and T2a in 14 with a median size of 26.5cm (range, 1149cm). The histology was adenocarcinoma in 20 cases, squamous cell carcinoma in 11, other histologies in two, and clinically diagnosed in seven. The median follow-up period was 23 months. Complete response was achieved in 3 (7.5%) patients after treatment and partial response in 17 (42.5%) patients. A total of 40 patients, the 2-year and 3-year local control rates were 87.3% and 81.8%, respectively. The 2-year and 3-year overall survival rates were 78.9% and 66.7%, respectively. During the follow-up, local progression occurred in three patients (7.5%). Seven patients developed distant metastasis, 2 developed carcinomatous pleurisy, 2 developed intrapulmonary metastasis, and 2 developed lymph node metastasis. Eight patients have died so far. In 5 patients, death was a result of disease progression. One patient died of interstitial pneumonia unrelated lung irradiation and 1 patient died of cerebral hemorrhage and unknown cause in 1 patient. Three patients experienced Grade 3 pneumonitis, but no more severe adverse events (grade 3) have yet been observed in any patients. Conclusion: We have introduced AHypoFR for small central lung tumors in order to improve outcomes than conventional radiation therapy and to reduce toxicities than SBRT. Our report is one of the best results at the
3138 Cone Beam Computed Tomography in Lung Stereotactic Ablative Radiation Therapy: Predictive Parameters of Early Response F. Alongi,1 R. Mazzola,1 F. Ricchetti,1 A. Fiorentino,1 S. Fersino,1 N. Giaj Levra,1 U. Tebano,2 G. Sicignano,1 S. Naccarato,1 and R. Ruggieri1; 1 Radiation Oncology Department Sacro Cuore Hospital, Negrar-Verona, Italy, 2Radiation Oncology School, University of Padova, Padova, Italy Purpose/Objective(s): To analyze lung lesion volume variations by contouring on cone-beam computed tomography (CBCT) images to evaluate early predictive parameters of stereotactic ablative radiation therapy (SABR) treatment response. Materials/Methods: The prescribed dose of SABR varied according to the tumor site (central or peripheral) and maximum diameter of the lesions using a strategy of risk-adapted dose prescription with a range of dose between 48 and 70 Gy in 3-10 consecutive fractions. For the purpose of the analysis, gross tumor volume (GTV) was re-contoured for each patient at first and last CBCT using 2 lung levels/window: a) -600/1000 Hounsfield Units (HU), b) -1000/250 HU. Univariate analysis was performed to evaluate a correlation between lung lesions variations on CBCT using the two window levels with the treatment response 6 months after SABR. The analysis was conducted considering the following variables: number of fractions, time between initial and final fraction, BED, Pre-SABR GTV volume. Cut-points of lesion volume reduction were evaluated to determine the correlation with lung lesions complete response six months after SABR. Results: Forty-one lung lesions were evaluated. Eighty-two lung lesions were re-contoured for each CBCT levels/window. A lung lesions shrinkage of at least 20% revealed to be statistically correlated to lesions complete response six months after SABR for both the CBCT levels/windows used. The probability of complete response ranged between 6 and 8 times higher in respect to the CBCT lung level adopted comparing to patients without a GTV decrease of 20%. Conclusion: Early predictive parameters of SABR efficacy could be helpful for clinicians in order to improve patient-tailored surveillance and management. According to current findings, a lung lesion shrinkage at least of 20% at last session of SABR could be predictable for early complete response. Further investigations are needed. Author Disclosure: F. Alongi: None. R. Mazzola: None. F. Ricchetti: None. A. Fiorentino: None. S. Fersino: None. N. Giaj Levra: None. U. Tebano: None. G. Sicignano: None. S. Naccarato: None. R. Ruggieri: None.
3139 The Safety of Critical Structures Throughout Treatment for DoseEscalated Locally Advanced Non-Small Cell Lung Cancer Patients T.B. Nielsen,1 M. Nielsen,1 T. Schytte,2 C. Brink,1,3 O. Hansen,2 and R.S. Thing3; 1Laboratory of Radiation Physics, Odense University Hospital, Odense, Denmark, 2Department of Oncology, Odense University Hospital, Odense, Denmark, 3Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Purpose/Objective(s): In the ongoing multi-center trial NARLAL2 by the Danish Oncologic Lung Cancer Group, patients with locally-advanced NSCLC are randomized to standard homogeneous treatment of 66 Gy/33 fractions and inhomogeneous dose-escalated treatment in 33 fractions. The