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62 Upper abdominal organ motion during conformal radiotherapy for gastric carcinoma
CARO 2 0 0 6
Results: The records of 80 patients were reviewed. The mean age was 58 years (range 22-75), with 53 (66%) males. Stage distribution was: IB - 13 (16%), II - 32 (40%), I I I A - 24 (30%), IIIB - 4 (9%) and IV - 7 (9%). 45 Gy in 25 fractions was delivered with a conformal technique. Bolus 5FU and folinic acid was given in 69; 11 received investigational 5FU and Cisplatin in escalating dose. All treatment was completed in 56 (70%) patients; nine (11%) did not complete radiotherapy and 22 (27.5 %) had chemotherapy dose omissions. Median follow up is 30 months (range 6-62). At two years, overall survival was 84% (95% CI 73%-90%). Mean V30 (volume receiving 30 Gy or more) for liver was 31%, whereas mean V22.5 was 31%, 18% and 25% for left kidney, right kidney and combined volume of both kidneys, respectively. Mean of means was 22 Gy for liver and 15 Gy for kidneys. Late toxicity occurred in six patients at nine to 53 months following treatment: bowel obstruction/ perforation (2) and anastomotic stricture (4), in volumes treated to 45 Gy. There was no clinical renal or hepatic toxicity. Grade 1 (CTCAE v3.0) creatinine elevation was observed in eight (10%) patients; at least one liver test was altered in 22 (27.5%): grade 1-17; 2-4; 3-1. Abnormal bloodwork occurred nine days to 55 months after treatment and did not correlate with higher kidney and liver doses. Conclusions: In our cohort of patients treated with radiochemotherapy, small bowel and anastomotic toxicity prevailed, with no clinical renal or hepatic toxicity observed. Biochemical renal and hepatic changes were not related to clinical toxicity or dose delivered. 62 Upper Abdominal Organ Motion During Conformal Radiotherapy for Gastric Carcinoma B. Wysocka, Z. Kassam, G. Lockwood, L. Dawson, J. Brierley, J. Ringash Princess Margaret Hospital, University of Toronto, Toronto, Ontario Barbara. Wysocka@rmp. uh n. on. ca
Aim: To determine respiratory and interfraction organ motion in gastric cancer patients receiving adjuvant radiochemotherapy. Methods: Abdominal CTs in free breathing (FB), inhale (I) and exhale (E) states were obtained on 17 patients in weeks one, three and five of post-operative gastric cancer treatment with BodyFix immobilization. Images from 138 scans were registered to the planning CT using automated bone registration. Volumes of interest (VOI) were contoured [right (RK) and left (LK) kidney, liver (L), stomach (S), pancreas (P), celiac axis (C) and porta-hepatis (PH) and the centre of mass of each organ was identified as a point of interest (POI). POIs were also placed at dome of diaphragm (D) and splenic hilum (SH). Organ motion was measured using the difference of POI position in cranial-caudal (CC), anterior-posterior (AP) and right-left (RL) directions. Inhale and exhale positions at each time point were used to determine respiratory motion. Interfractional motion at weeks one, three and five was determined and compared to planning (FB) or week one (I, E) scan. Results: Respiratory motion is maximal in the CC direction with median absolute displacements of: SH 24, LK 20.8/RK 19.6, D 20.5, L 16.1, S 15.5, P 15.1, PH 12 and C 3.Smm. In the AP direction, the greatest median displacement was: SH 9.4ram and in the RL direction motion was less (maximal for PH and SH, 2.9ram). Median absolute respiratory displacement for all organs was: 17.5mm CC, 5.9mm AP, and 2.7ram RL. Median interfraction displacement (range, mm) for all organs was: CC 4.6 (0-38), AP 2.2 (0-20.5), RL 2.2 (0-37.1) in FB; CC 6.3 (0-36), AP 3.8 (0.1-16.6), RL 2.5 (0-19.6) in I and CC 6 (046), RL 2.6 (0-19.4), AP 2.3 (0-12.9) in E. Conclusions: 1) Organ motion in upper abdomen can be substantial and should be incorporated in the planning target volume for conformal or IMRT planning. 2) Median interfraction organ position variability is substantial and similar for all phases of breathing.
September 13-16
$19
63 Primary and Adjuvant Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase I / I I Study with Long Term Outcome A.M. Brade, C. Townsley, C. Brezden-Masley, D. Hedley, M. MacLean, S. Gallinger, G, Pond, A.M. Oza, M.J. Moore, J. Brierley Princess Margaret Hospital, University of Toronto, Toronto, Ontario anthony, brade@rm p. uhn. on. ca
Objectives: Gemcitabine (G) is active against pancreatic carcinoma and is a potent radiosensitizer. We present extended follow-up data from a Phase I/II study of patients treated with combination Gemcitabine and radiation (GRT). Methods: Eligible patients had either LA or high risk resected (R) pancreatic cancer (positive nodes or positive margin). Twenty-eight were enrolled in a Phase I study of increasing doses of radiotherapy (35 Gy [n=7]/43.75 Gy [n=11]/52.5 Gy (n=10) given over 4, 5 or 6 weeks, respectively in 1.75 Gy fractions) concurrently with 40 mg/m 2 gemcitabine biweekly. Subsequently 35 were treated with induction G 1000 rag/m2 7/8 weeks followed by concurrent bi-weekly Gemcitabine (40 mg/m2) with 52.5 Gy (30 fractions of 1.75 Gy over six weeks). In total there were 63 patients (30 LA and 33 R) treated between March 1999 - July 2001. Results: In the LA population the best response observed was CR - 1, PR - 2, SD - 10, PD - 10. GRT was not delivered to eight patients due to progression on G alone (n=5) or patient request (n=3). By intent to treat analysis, the median survival in LA disease was 14.5 months and two-year survival was 17%. In the resected population the median time to progression was 8.3 months, the median survival was 17.9 months and the two and five-year survival rates were 36 and 19%. The, treatment was generally well tolerated during both the induction G and the GRT. Episodes of Gr 3/4 toxicity on GRT (n=55): leukopenia - 10/0, lympho-penia - 8/13, neutropenia - 8/0, thrombocytopenia 4/0, fatigue 9/0, pain 5/0, nausea/vomiting 8/0. Episodes of Gr 3/4 toxicity on induction G (n=35): leukopenia - 1/0, lymphopenia - 1/0, neutropenia 5/3, fatigue - 1/0, pain - 5/1, nausea/vomiting - 1/0. Conclusion: Survival for both LA and HR patients with this concurrent gemcitabine radiotherapy regimen is promising and warrants further investigation. 64 Phase I Study of Stereotactic Radiotherapy for Unresectable Primary and Metastatic Liver Cancer L. Dawson, M. Hawkins, C. Eccles, T. Craig, J-P. Bissonnette, G. Lockwood, J. Zhang, J. Kim, B. Cummings, M. Sherman, J. Knox, S. Gallinger Princess Margaret Hospital, University of Toronto, Toronto, Ontario laura, dawson~rmp, uhn. on. ca
Purpose: To report results of a Phase I study of highly individualized, stereotactic radiotherapy (SRT) in unresectable liver cancer. M e t h o d s : Eligible patients had unresectable or medically inoperable hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CC) and liver metastases (LM), liver enzymes <6 fold higher than normal and Child score A. Patients were stratified based on diagnosis (primary, metastatic) and effective liver volume irradiated (low <20%, mid 20-50%, high 50-80%). Patients were treated with breath hold if feasible and daily image guidance. SRT was delivered in six fractions. The dose was individualized to maintain the same nominal estimated risk of classic radiation-induced liver disease (RILD) at three levels (I - 5% risk, II - 10% risk, I l I - 20%, maximum dose 60 Gy). Results: From August 2003 to March 2006, 82 maximally pretreated patients initiated SRT. Three patients discontinued treatment early due to a variceal bleed (HCC), sepsis (CC) and progressive disease (LM). Seventy-nine patients completed SRT (34 LM, 33 HCC, 12 CC). The median age was 64 years (38-92 years). The median tumour volume was 293 cc (2.9-3088 cc).
Results: The records of 80 patients were reviewed. The mean age was 58 years (range 22-75), with 53 (66%) males. Stage distribution was: IB - 13 (16%), II - 32 (40%), I I I A - 24 (30%), IIIB - 4 (9%) and IV - 7 (9%). 45 Gy in 25 fractions was delivered with a conformal technique. Bolus 5FU and folinic acid was given in 69; 11 received investigational 5FU and Cisplatin in escalating dose. All treatment was completed in 56 (70%) patients; nine (11%) did not complete radiotherapy and 22 (27.5 %) had chemotherapy dose omissions. Median follow up is 30 months (range 6-62). At two years, overall survival was 84% (95% CI 73%-90%). Mean V30 (volume receiving 30 Gy or more) for liver was 31%, whereas mean V22.5 was 31%, 18% and 25% for left kidney, right kidney and combined volume of both kidneys, respectively. Mean of means was 22 Gy for liver and 15 Gy for kidneys. Late toxicity occurred in six patients at nine to 53 months following treatment: bowel obstruction/ perforation (2) and anastomotic stricture (4), in volumes treated to 45 Gy. There was no clinical renal or hepatic toxicity. Grade 1 (CTCAE v3.0) creatinine elevation was observed in eight (10%) patients; at least one liver test was altered in 22 (27.5%): grade 1-17; 2-4; 3-1. Abnormal bloodwork occurred nine days to 55 months after treatment and did not correlate with higher kidney and liver doses. Conclusions: In our cohort of patients treated with radiochemotherapy, small bowel and anastomotic toxicity prevailed, with no clinical renal or hepatic toxicity observed. Biochemical renal and hepatic changes were not related to clinical toxicity or dose delivered. 62 Upper Abdominal Organ Motion During Conformal Radiotherapy for Gastric Carcinoma B. Wysocka, Z. Kassam, G. Lockwood, L. Dawson, J. Brierley, J. Ringash Princess Margaret Hospital, University of Toronto, Toronto, Ontario Barbara. Wysocka@rmp. uh n. on. ca
Aim: To determine respiratory and interfraction organ motion in gastric cancer patients receiving adjuvant radiochemotherapy. Methods: Abdominal CTs in free breathing (FB), inhale (I) and exhale (E) states were obtained on 17 patients in weeks one, three and five of post-operative gastric cancer treatment with BodyFix immobilization. Images from 138 scans were registered to the planning CT using automated bone registration. Volumes of interest (VOI) were contoured [right (RK) and left (LK) kidney, liver (L), stomach (S), pancreas (P), celiac axis (C) and porta-hepatis (PH) and the centre of mass of each organ was identified as a point of interest (POI). POIs were also placed at dome of diaphragm (D) and splenic hilum (SH). Organ motion was measured using the difference of POI position in cranial-caudal (CC), anterior-posterior (AP) and right-left (RL) directions. Inhale and exhale positions at each time point were used to determine respiratory motion. Interfractional motion at weeks one, three and five was determined and compared to planning (FB) or week one (I, E) scan. Results: Respiratory motion is maximal in the CC direction with median absolute displacements of: SH 24, LK 20.8/RK 19.6, D 20.5, L 16.1, S 15.5, P 15.1, PH 12 and C 3.Smm. In the AP direction, the greatest median displacement was: SH 9.4ram and in the RL direction motion was less (maximal for PH and SH, 2.9ram). Median absolute respiratory displacement for all organs was: 17.5mm CC, 5.9mm AP, and 2.7ram RL. Median interfraction displacement (range, mm) for all organs was: CC 4.6 (0-38), AP 2.2 (0-20.5), RL 2.2 (0-37.1) in FB; CC 6.3 (0-36), AP 3.8 (0.1-16.6), RL 2.5 (0-19.6) in I and CC 6 (046), RL 2.6 (0-19.4), AP 2.3 (0-12.9) in E. Conclusions: 1) Organ motion in upper abdomen can be substantial and should be incorporated in the planning target volume for conformal or IMRT planning. 2) Median interfraction organ position variability is substantial and similar for all phases of breathing.
September 13-16
$19
63 Primary and Adjuvant Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Phase I / I I Study with Long Term Outcome A.M. Brade, C. Townsley, C. Brezden-Masley, D. Hedley, M. MacLean, S. Gallinger, G, Pond, A.M. Oza, M.J. Moore, J. Brierley Princess Margaret Hospital, University of Toronto, Toronto, Ontario anthony, brade@rm p. uhn. on. ca
Objectives: Gemcitabine (G) is active against pancreatic carcinoma and is a potent radiosensitizer. We present extended follow-up data from a Phase I/II study of patients treated with combination Gemcitabine and radiation (GRT). Methods: Eligible patients had either LA or high risk resected (R) pancreatic cancer (positive nodes or positive margin). Twenty-eight were enrolled in a Phase I study of increasing doses of radiotherapy (35 Gy [n=7]/43.75 Gy [n=11]/52.5 Gy (n=10) given over 4, 5 or 6 weeks, respectively in 1.75 Gy fractions) concurrently with 40 mg/m 2 gemcitabine biweekly. Subsequently 35 were treated with induction G 1000 rag/m2 7/8 weeks followed by concurrent bi-weekly Gemcitabine (40 mg/m2) with 52.5 Gy (30 fractions of 1.75 Gy over six weeks). In total there were 63 patients (30 LA and 33 R) treated between March 1999 - July 2001. Results: In the LA population the best response observed was CR - 1, PR - 2, SD - 10, PD - 10. GRT was not delivered to eight patients due to progression on G alone (n=5) or patient request (n=3). By intent to treat analysis, the median survival in LA disease was 14.5 months and two-year survival was 17%. In the resected population the median time to progression was 8.3 months, the median survival was 17.9 months and the two and five-year survival rates were 36 and 19%. The, treatment was generally well tolerated during both the induction G and the GRT. Episodes of Gr 3/4 toxicity on GRT (n=55): leukopenia - 10/0, lympho-penia - 8/13, neutropenia - 8/0, thrombocytopenia 4/0, fatigue 9/0, pain 5/0, nausea/vomiting 8/0. Episodes of Gr 3/4 toxicity on induction G (n=35): leukopenia - 1/0, lymphopenia - 1/0, neutropenia 5/3, fatigue - 1/0, pain - 5/1, nausea/vomiting - 1/0. Conclusion: Survival for both LA and HR patients with this concurrent gemcitabine radiotherapy regimen is promising and warrants further investigation. 64 Phase I Study of Stereotactic Radiotherapy for Unresectable Primary and Metastatic Liver Cancer L. Dawson, M. Hawkins, C. Eccles, T. Craig, J-P. Bissonnette, G. Lockwood, J. Zhang, J. Kim, B. Cummings, M. Sherman, J. Knox, S. Gallinger Princess Margaret Hospital, University of Toronto, Toronto, Ontario laura, dawson~rmp, uhn. on. ca
Purpose: To report results of a Phase I study of highly individualized, stereotactic radiotherapy (SRT) in unresectable liver cancer. M e t h o d s : Eligible patients had unresectable or medically inoperable hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (CC) and liver metastases (LM), liver enzymes <6 fold higher than normal and Child score A. Patients were stratified based on diagnosis (primary, metastatic) and effective liver volume irradiated (low <20%, mid 20-50%, high 50-80%). Patients were treated with breath hold if feasible and daily image guidance. SRT was delivered in six fractions. The dose was individualized to maintain the same nominal estimated risk of classic radiation-induced liver disease (RILD) at three levels (I - 5% risk, II - 10% risk, I l I - 20%, maximum dose 60 Gy). Results: From August 2003 to March 2006, 82 maximally pretreated patients initiated SRT. Three patients discontinued treatment early due to a variceal bleed (HCC), sepsis (CC) and progressive disease (LM). Seventy-nine patients completed SRT (34 LM, 33 HCC, 12 CC). The median age was 64 years (38-92 years). The median tumour volume was 293 cc (2.9-3088 cc).