I. J. Radiation Oncology d Biology d Physics
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Volume 81, Number 2, Supplement, 2011
A Retrospective Study of Local Control and Survival for Esophageal Squamous Cell Carcinoma Treated with Three-Dimensional Conformal Radiotherapy (3DCRT)
C. Han, J. Li, S. Zhu, Z. Liu, Y. Wang, W. Shen, J. Su, J. Wang The Fourth Hospital of Hebei Medical University, Shijiazhuang, China Purpose/Objective(s): Locally advanced esophageal carcinoma (LAEC) is associated with poor survival and more effective treatments are needed. The aim of this study was to investigate the long-term outcomes and explore particular imaging prognostic factors of LAEC treated with 3DCRT. Materials/Methods: From July 200l to December 2006, 375 patients with unresectable LAEC (without distance metastases) received definitive 3DCRT as primary treatment was retrospectively analyzed. There were 240 male and 135 female patients with a median age of 67 years (range 38-87). Primary tumors were all squamous cell carcinoma located in cervical- (18), upper- (115), middle- (182) and lower-thoracic (60) esophagus. The median length of primary tumor was 5.5cm (range1.0-15cm). Clinical TNM stages were: stage I = 9, stage II = 106, stage III = 158 and stage IV = 102. Kaplan-Meier method was used for local control rate and overall survival (OS) analysis. Multivariate analysis with Cox regression model was used to assess independent prognostic factors with SPSS 11.0 software package. Results: Of all patients, 94.7% were followed up for a median of 26 months by December 2010. The 1, 3, 5-year locally regional control rates were 80.5%, 53.7%, 44.9%, respectively. The 1,3, 5-year OS rates and medial survival were 67.2%, 29.4%, 19.0% and 19 months, respectively. Univariate analysis showed that significant prognostic factors included tumor length, largest diameter of tumor in CT, clinical TNM stage, short-term effect of completed treatment, grades of acute radiation esophagitis and pneumonitis (Table). The OS rates of patients with esophagitis . = 2 grade was significantly different from those with \2 grade (X2 = 7.13, P = 0.008).Multivariate analysis revealed tumor length (X2 = 1.334, P = 0.031), clinical TNM stage (X2 = 18.000, P = 0.000), esophagitis (X2 = 1.175, P = 0.011) and chemotherapy (X2 = 4.874, P = 0.027) were independent prognostic factors. 291 patients passed away at the end of follow-up, due to locally regional relapse 145 (40.8%), distance metastases 90(30.9%), local and distance failures 25(8.6%), and non-tumor death 31 (10.7%). Conclusions: The locally regional control rate has been improved with 3DCRT although there is no benefit for long-term survival. Our data indicated tumor length, clinical stage, acute radiation esophagitis and chemotherapy were the independent prognostic factors for LAEC. Table Variables Length of tumor(cm) \ = 5.0 5.1-7.0 .7.1 Largest diameter of tumor(cm) \ = 4.0 .4.1 Clinical TNM stage I II III IV
No. cases
1-year
Survival 3-year
rates(%) 5-year
X2
P
170 114 91
79.4 61.3 48.3
39.4 25.5 10.3
23.8 18.8 5.1
18.52
0.000
193 182
80.2 53.8
39.6 16.5
25.4 10.3
30.24
0.000
9 106 158 102
100 84.1 69.8 42.7
67.8 45.5 28.8 10.3
53.5 28.5 16.3 5.0
75.68
0.000
Author Disclosure: C. Han: None. J. Li: None. S. Zhu: None. Z. Liu: None. Y. Wang: None. W. Shen: None. J. Su: None. J. Wang: None.
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High-dose-rate Intraluminal Brachytherapy Combined with External Beam Radiation Therapy for Medically Inoperable Patients with Stage I Thoracic Esophageal Cancer
H. Ishikawa1, S. Noda1, T. Tamaki1, T. Nonaka2, T. Ebara1, H. Katoh1, T. Kaminuma1, T. Sato1, T. Takahashi1, T. Nakano1 1 Gunma University Graduate School of Medicine, Maebashi Gunma 371-8511, Japan, 2Kanagawa Cancer Center, Yokohama, Japan
Purpose/Objective(s): Brachytherapy has possibility to improve the local tumor control without increasing the side-effects of the organs at risk. The aim of this study is to analyze the effects of high-dose-rate intraluminal brachytherapy (HDR-IB) boost following external beam radiotherapy (EBRT) on the clinical outcomes for medically inoperable patients with Stage I esophageal cancer in radiation therapy. Materials/Methods: Between 1997 and 2010, 40 patients (34 males and 6 females) with stage I (T1N0M0) squamous cell carcinoma at the thoracic esophagus received definitive radiation therapy alone. Median age of the subjects was 72 years (range, 4986), and tumors were located at upper-, middle-, and lower-thoracic esophagus in 5, 25, and 10, respectively. The examination using endoscopic ultrasound revealed that 6 patients had mucosal cancer (MC) but 34 tumors showed submucosal cancer (SMC). The total EBRT dose of 56 Gy and 60 Gy with a conventional daily fractionation dose at 2 Gy were given for MC and SMC, respectively. In HDR-IB using an Ir-192 source, the prescribed dose was 9 Gy (3 Gy x 3 times) over 10 days. Median follow-up time was 41 months (range, 7-120 months), and clinical outcomes were investigated. Results: Recurrences were noted in 9 (26%) of 34 SMC patients but in 1 (17%) of 6 MC patients. Of 10 recurrence tumors, 8 were determined as local recurrences (infield in 6, outfield in 3), 1 as regional recurrence, and 1 as lung metastasis as an initial recurrence. Salvage therapy such as curative surgery and endoscopic mucosal resection was performed for patients with loco-regional recurrence, and 7 were successfully rescued. At the last follow-up, 3 patients had died of tumor recurrence and 11 patients had
Proceedings of the 53rd Annual ASTRO Meeting died of intercurrent diseases without evidence of recurrence. In addition, another patient died of treatment related death because of esophageal fistula. The 5-year cause-specific survival (CSS) and the loco-regional control (LRC) rates were 84% and 73%, respectively. The use of HDR-IB tended towards statistical significance for CSS (p = 0.07), if compared with 19 patients who received EBRT alone during the period of this study (59%). For cardio-pulmonary adverse effects, Grade 1 and Grade 2 toxicities were observed in 3 and 2 patients, respectively, but no Grade 3 or severe toxicities developed. Conclusions: Radiation therapy alone using HDR-IB is very effective and tolerable for Stage I thoracic esophageal cancer, even in patients with SMC. Severe cardio-pulmonary adverse events in this study were much less than those reported by recent studies using concurrent chemoradiotherapy Author Disclosure: H. Ishikawa: None. S. Noda: None. T. Tamaki: None. T. Nonaka: None. T. Ebara: None. H. Katoh: None. T. Kaminuma: None. T. Sato: None. T. Takahashi: None. T. Nakano: None.
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Does 3-D CRT Plan Become a Clinical Relevant Factor to Radiation Pneumonitis Risk in Patients with Esophageal Cancer Treated with Definitive Chemoradiotherapy?
M. Myojin1, S. Tanabe1, M. Hosokawa1, S. Shimizu2 Keiyukai Sapporo Hospital, Sapporo 003-27, Japan, 2Hokkiado University School of Medicine, Sapporo, Japan
1
Purpose/Objective(s): For definitive chemoradiotherapy (CRT) in patients (pts.) with SCC of the thoracic esophagus, it is believed in Japan that all of the three-field (neck, thorax and abdomen) lymphatics should be evenly included in the CTV because of the advanced surgical data on three-field lymph node dissection. To reduce radiation pneumonitis (RP) risk, we evaluated onearm cohort for the 3-D CRT plan, which was developed for the reduction of peripheral lung dose, by a review of the consecutive series including historical control pts. with conventional treatment plan. Materials/Methods: We retrospectively reviewed the records of 260 consecutive patients who were treated with definitive CRT (50.4Gy/28F 3-regional RT+ 2 cycles of FP +/- 9Gy/5F boost RT) between Sep. 2004 and Oct. 2010. After we ruled out those who had passed away from cancer without RP within less than 4 months from the beginning, 244 (Age 37-80, median 66.5) out of the 260 records were available for this study. RP were defined as ARDS and pneumonitis in CTCAE ver. 4. Every grade 2-5 RP has been observed from 1.6 to 5 months from the beginning in this series. From June 2009, eighty-four pts. of the 244 were enrolled to a cohort for the treatment plan in 3-D CRT different from conventional method for the 50.4Gy to the CTV covering the three-field lymphatics. The new treatment plan consisted of basic AP-PA and supporting two oblique beams separated vertically at the spinal curvature (weight; upper 10-12% and lower 20-22%). Those plans were characterized that V5 and V10 were significantly lower than the conventional plans (AP-PA , and RAO-LPO after 40Gy) in our other presentation. To clarify the clinical relevant factors to improve RP risk, Fisher’s exact method and logistic regression analysis were available for statistics. Results: We had experienced 9 RP(Grade 5: 2, Grade 4: 2, Grade 3: 3, and Grade 2: 2) cases in this study . There was no RP in the cohort group. Statistical analyses between onset of RP and each of several independent factors; age ($71 vs. #70; n 75:169), COPD/ respiratory disorder (+ vs. -; n 17:227), gender (M vs. F; n 220:24), RT dosage (50.4Gy vs. 59.4Gy; n 52:192), chemo. cycles (2 vs.1; n 210:34), main tumor location (mid-thoracic vs. other thoracic) and 3D CRT plan (cohort vs. conventional; n 84:160) resulted that age and 3D CRT plan are significant factors to RP risk (age; p = 0.013 and 3D CRT plan; p = 0.032 in a logistic regression analysis). Conclusions: The causal relationship between RP and RT dose distribution was confirmed in the practice under the environment of intensive CRT. Author Disclosure: M. Myojin: None. S. Tanabe: None. M. Hosokawa: None. S. Shimizu: None.
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Retrospective Review of the Dosimetric and Treatment-Related Determinants of Toxicity in Patients with Esophageal Cancer Treated with Concurrent Chemoradiation with or without Surgery
R. Shiloh1, S. S. Rakhra1, J. Evans2, I. Helenowski2, Z. Kang1, M. F. Mulcahy1, W. Small1, J. P. Hayes1 1
Northwestern Memorial Hospital, Chicago, IL, 2Northwestern University Feinberg School of Medicine, Chicago, IL
Purpose/Objective(s): To investigate the dosimetric determinants and the effects of different radiotherapy techniques on acute and late pulmonary and cardiac toxicity in patients with esophageal cancer. Materials/Methods: Between January 2003 and November 2010, 71 patients treated at our institution met criteria of our IRBapproved protocol. Eligibility included patients of all ages with esophageal cancer of any stage or histology treated with definitive multimodality therapy that included radiotherapy. Data collected for each patient included cancer stage and histology, chemotherapy regimen, RT technique, surgical status, dose-volume histograms, acute and late toxicity based on CTCAE 4.0 criteria, and survival. DVH values were calculated with and without heterogeneity correction. Results: The median mean lung dose (heterogeneity corrected) was 1315 cGy for AP/PA with off-cord boost and 1227 cGy for multi-field conformal (MFC) radiation therapy (p = 0.44). The median lung V20 (heterogeneity corrected) was 20.4% for AP/PA/ off-cord boost and 21.7% for MFC (p = 0.85). The median mean heart dose (heterogeneity corrected) was 3593 cGy for AP/PA/ off-cord boost and 3398 cGy for MFC (p = 0.08). Only Heart V30 (AP/PA/off-cord boost 72.5% vs. MFC 58.0%, P = 0.02) and V40 (AP/PA/off-cord boost 51.0% vs. MFC 34.7%, p = 0.04) had statistically significant differences between the two techniques. There was no significant difference when DVH parameters were calculated with heterogeneity correction. There was 1 case of grade 3/4 acute lung toxicity (1.4%), 5 cases of grade 3/4 late lung toxicity (7.0%), 1 case of grade 3/4 acute cardiac toxicity (1.4%), and 4 cases of grade 3/4 late cardiac toxicity (5.6%). No DVH parameter was significantly associated with increased risk of any toxicity. Twenty two patients (31.0%) had surgery after chemoradiation. Those patients who had surgery had a higher rate of late grade 3/4 cardiac toxicity than those who did not have surgery (18.2% vs. 0%, p = 0.008). No cardiac DVH parameters were significantly associated with toxicity in the subset of patients who ultimately underwent surgery. Overall survival at 3 years was 57.0% for Stage I/II, 40.5% for Stage III, and 10.2% for Stage IV (p = 0.045). There was no significant difference in survival based on histology.
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