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1068 poster PREOPERATIVE CAPECITABINE, RADIATION AND BEVACIZUMAB IN RECTAL CANCER: FINAL RESULTS OF THE CRAB PHASE II TRIAL
R ECTAL CANCER
of p53 immunohistochemical staining of pretreatment biopsy specimens and pathohistological response to preoperative chemoradiotherapy. Materials: Between October 2006 and December 2008, 50 patients with locally advanced rectal cancer (T3 stage -76%, T4 stage - 24%) were treated with preoperative radiotherapy with total dose of 45 Gy combined with concomitant chemotherapy Mitomycin C and Capecitabine. Surgery was performed six to eight weeks after the end of chemoradiation. p53 immumohistochemical staining was performed on pretreatment biopsy specimens in all patients and results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system. p53 was considered overexpressed when ≥10% of the malignant nuclei was positive. If fewer than 10% of the nuclei were stained, the specimen was scored as having normal p53 expression. Results: All patients underwent surgery. At pathologic examination, 8(16%) of 50 patients had a pathologic complete response (pCR), 8 (16%) were pT2, 32 (64 %) pT3 and 2 (4%) pT4. Positive lymph nodes were detected in 22 (44%) patients. Overall, 48% of patients had major tumor downstaging. Out of 50 pts, overexpression was noted in 33 pts (66%) and 17 pts (34%) had normal exspression on biopsy specimen. After surgical resection pathological complete response (pCR) was noted in 2pts(11,76%) with normal p53 expression and in 6 pts(18,18%) with p53 overexpression, but we didnt find statistical significant diference between tested groups (p=0.699). Conclusions: We did not find correlation between p53 overexpression and histopathological response to preoperative chemoradiotherapy. The same result was obtained by majority of other published studies until now.
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chemotherapy, followed by Capecitabine-based chemoradiation in patients with resected stage IB-IIIB gastric carcinoma. Materials: Patients with localized stage IB-IIIB resected gastric carcinoma, one month after gastrectomy, were treated with 3-weekly Irinotecan (65mg/m2) and Cisplatin (30mg/m2) for two courses, followed by 3D conformally planned radiotherapy (total dose 5040cGy in 28 fractions) concurrently with Capecitabine 1000mg/m2 divided in two doses as radiosensitizer. Patients received an additional course of chemotherapy upon completion of radiation therapy. Results: Between April 2005 and December 2009, 84 patients were enrolled in the study. There were 53 men and 31 women with median age at diagnosis of 56 years (range 37-78 years). Seventy-one of them had total gastrectomy with extensive lymphadenectomy and thirteen had subtotal gastrectomy. The most common hematological toxicity was grade 2 neutropenia in 60% of the patients, Grade 2 aneamia and thrombocytopenia occurred in 35% and 38% and Grade 2 nausea and vomiting in 40% of the patients. With a median follow-up of 39 months (9-58 months) 6 patients relapsed locally (7%), 4 developed small volume peritoneal deposits (5%) and 7 developed distant metastases (8%). Five year overall survival was 66% and disease-free survival 48%. Conclusions: Our results, indicate that the combination of postoperative Irinotecan and Cisplatin chemotherapy followed by chemoradiation (Capecitabine-based) is an effective and safe regimen with moderate toxicity for patients with resected adenocarcinoma of the stomach. 1068 poster
1066 poster PALLIATIVE RADIOTHERAPY INSTEAD OF SURGERY IN SYMPTOMATIC RECTAL CANCER WITH SYNCHRONOUS UNRESECTABLE METASTASES D. Tyc-Szczepaniak1 , L. Wyrwicz2 , M. Olszyna-Serementa1 , L. Pietrzak1 , J. ´ 2 , A. Rutkowski2 , K. Bujko1 Krynski 1 M ARIA S KLODOWSKA -C URIE M EMORIAL C ANCER C ENTRE, Department of Radiotherapy, Warsaw, Poland 2 M ARIA S KLODOWSKA -C URIE M EMORIAL C ANCER C ENTRE, Department of Gastrointestinal Cancer, Warsaw, Poland Purpose: Apart from chemotherapy, palliative primary tumour resection or diverting stoma creation is currently a standard method of management for patients with symptomatic rectal cancer and nonresectable synchronous distant metastases. The potential advantage of using conservative treatment over surgery is to avoid stoma and postoperative complications. In the frame of a prospective study, we aim to answer the question as to whether surgery can be avoided by using short-course pelvic irradiation and immediate consolidation chemotherapy. Materials: Patients with symptomatic mid and low-lying rectal cancer and unresectable distant metastases received 5 x 5 Gy to the pelvis and oxaliplatinebased chemotherapy after one week. Planning target volume included only gross tumour with a margin. The effectiveness of local treatment was assessed by the self-administered questionnaires filled out by patients. Results: All twenty-one consecutive patients (planned sample size) who fulfilled the entry criteria were enrolled into our study between December 2009 and September 2010. Tumour obstructive symptoms were most frequently reported (62%). One month after radiotherapy, 38% of patients reported complete relief from pelvic symptoms, 57% reduction of symptom’s intensity and 5% (one patient) had stoma creation. At the last follow-up, two patients (10%) had stoma. The remaining 19 patients (90%) did not need surgery during follow-up which ranged from 1 to 9 months; with the median of 6 months. In the last questionnaire, 37% of these patients reported complete relief from pelvic symptoms, 47% partial response and 16% improvement with consecutive progression of symptoms but without a need for surgery. Seven patients died within 1 to 8 months (median 3) post radiation. Of these, six patients had their pelvic symptom controlled and did not require surgery and one patient had a stoma. Updated results will be presented at the conference. Conclusions: For symptomatic rectal cancer patients with unresectable distant metastases, pelvic radiation with consolidation chemotherapy represents a promising approach. 1067 poster POSTOPERATIVE IRINOTECAN/CISPLATIN CHEMOTHERAPY FOLLOWED BY CHEMORADIATION FOR STAGE IB-IIIB GASTRIC CANCER. E. Diamantidou1 , L. Vini2 , D. Hourmouzi3 , C. Kakana4 , A. Silyvridou5 1 I NTERBALKAN M EDICAL C ENTER, Medical Oncology, Thessaloniki, Greece 2 ATHENS M EDICAL C ENTRE, Radiation Oncology, Athens, Greece 3 I NTERBALKAN M EDICAL C ENTER, Radiology, Thessaloniki, Greece 4 I NTERBALKAN M EDICAL C ENTER, Medical Physics, Thessaloniki, Greece 5 ATHENS M EDICAL C ENTRE, Medical Physics, Athens, Greece Purpose: The aim of this prospective study was to evaluate toxicity and efficacy of postoperative adjuvant sequential Irinotecan and Cisplatin
PREOPERATIVE CAPECITABINE, RADIATION AND BEVACIZUMAB IN RECTAL CANCER: FINAL RESULTS OF THE CRAB PHASE II TRIAL V. Velenik1 , J. Ocvirk2 , M. Music3 , M. Bracko4 , F. Anderluh1 , I. Oblak1 , I. Edhemovic5 , E. Brecelj5 , M. Kropivnik3 , M. Omejc6 1 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Radiation Oncology, Ljubljana, Slovenia 2 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Medical Oncology, Ljubljana, Slovenia 3 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Radiology, Ljubljana, Slovenia 4 U NIVERSITY MEDICAL CENTER, Department of Pathology 5 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Surgery, Ljubljana, Slovenia 6 U NIVERSITY MEDICAL CENTER, Department of Surgery Purpose: We assessed the efficacy and safety of adding bevacizumab (Bev) to standard, capecitabine-based neoadjuvant radiochemotherapy (CRT) to increase the pathological remission rate of locally advanced rectal cancer as primary end point. Materials: Enrolled patients (pts) with MRI-confirmed stage II/III rectal cancer were treated with an infusion of Bev (5 mg/kg) 2 weeks prior to neoadjuvant CRT, followed by Bev 5 mg/kg on week 3, 5, 7 and capecitabine 825 mg/m2 bid including weekends during RT. RT was administred at 50.4 Gy (25x1.8 Gy with boost 3x1.8 Gy, 3d conformal technique), starting on week 3. Total mesorectal excision was scheduled 6-8 weeks after completition of CRT. Tumor regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was complete pathological response (pCR; TRG 4). Results: A total of 60 pts were eligible for analysis. Median age was 60 (range: 31-79) years, 64% of pts were male. Three pts presented with stage T2 (4.9%), 53 with stage T3 (86.9%), 5 with stage T4 (8.2%), and lymph node involvement was detected in 49 pts (80.3%). In 28 pts (45.9%) tumor invaded the mesorectal fascia. The median tumor distance from anal verge was 6 (range: 0-11) cm.Dose eduction or treatment interruption was required for 7 pts (11.6%) due to grade 2 (n=2) and grade 3 (n=2) leukopenia, grade 3 diarrhea (n=1), grade 3 (n=1) and grade 4 (n=1) vascular toxicity. Other grade 3 toxicities included dermatitis (n=6), proteinuria (n=4) and hypertension (n=1). Treatment was terminated in 1 pt due to withdrawal of the informed consent.Radical resection was achieved in 57 pts (95%) and 42 pts (70%) had sphincter preserving surgery. TRG 4 (pCR) was recorded in 8 pts (13.3%) and TRG 3 in 9 pts (15%). T-, N- and overall downstaging rates were 46.7%, 65% and 75%, respectively.Thirty-eight pts (62.3%) developed perioperative complications, most common delayed wound healing (n=18, 30%), infection/abscess (n=12, 20%) and anastomotic leak (n=7, 11.7%). Six pts required surgical reintervention for leak (n=3), abdominal abscess (n=2) and pneumothorax (n=1).Fifty pts (83.3%) received postoperative chemotherapy. Conclusions: The addition of Bev to standad capecitabine-based preoperative CRT is feasible and well tolerated. The high rate of radical resections suggests its potential effect on tumor downstaging. However, it is associated with considerable toxicity and with no clinically relevant increase in pCR rate. Longer follow-up is needed to assess the impact on other efficacy endpoints.
of p53 immunohistochemical staining of pretreatment biopsy specimens and pathohistological response to preoperative chemoradiotherapy. Materials: Between October 2006 and December 2008, 50 patients with locally advanced rectal cancer (T3 stage -76%, T4 stage - 24%) were treated with preoperative radiotherapy with total dose of 45 Gy combined with concomitant chemotherapy Mitomycin C and Capecitabine. Surgery was performed six to eight weeks after the end of chemoradiation. p53 immumohistochemical staining was performed on pretreatment biopsy specimens in all patients and results were compared with histopathological tumor regression according to a standardized semiquantitative score grading system. p53 was considered overexpressed when ≥10% of the malignant nuclei was positive. If fewer than 10% of the nuclei were stained, the specimen was scored as having normal p53 expression. Results: All patients underwent surgery. At pathologic examination, 8(16%) of 50 patients had a pathologic complete response (pCR), 8 (16%) were pT2, 32 (64 %) pT3 and 2 (4%) pT4. Positive lymph nodes were detected in 22 (44%) patients. Overall, 48% of patients had major tumor downstaging. Out of 50 pts, overexpression was noted in 33 pts (66%) and 17 pts (34%) had normal exspression on biopsy specimen. After surgical resection pathological complete response (pCR) was noted in 2pts(11,76%) with normal p53 expression and in 6 pts(18,18%) with p53 overexpression, but we didnt find statistical significant diference between tested groups (p=0.699). Conclusions: We did not find correlation between p53 overexpression and histopathological response to preoperative chemoradiotherapy. The same result was obtained by majority of other published studies until now.
S 397
chemotherapy, followed by Capecitabine-based chemoradiation in patients with resected stage IB-IIIB gastric carcinoma. Materials: Patients with localized stage IB-IIIB resected gastric carcinoma, one month after gastrectomy, were treated with 3-weekly Irinotecan (65mg/m2) and Cisplatin (30mg/m2) for two courses, followed by 3D conformally planned radiotherapy (total dose 5040cGy in 28 fractions) concurrently with Capecitabine 1000mg/m2 divided in two doses as radiosensitizer. Patients received an additional course of chemotherapy upon completion of radiation therapy. Results: Between April 2005 and December 2009, 84 patients were enrolled in the study. There were 53 men and 31 women with median age at diagnosis of 56 years (range 37-78 years). Seventy-one of them had total gastrectomy with extensive lymphadenectomy and thirteen had subtotal gastrectomy. The most common hematological toxicity was grade 2 neutropenia in 60% of the patients, Grade 2 aneamia and thrombocytopenia occurred in 35% and 38% and Grade 2 nausea and vomiting in 40% of the patients. With a median follow-up of 39 months (9-58 months) 6 patients relapsed locally (7%), 4 developed small volume peritoneal deposits (5%) and 7 developed distant metastases (8%). Five year overall survival was 66% and disease-free survival 48%. Conclusions: Our results, indicate that the combination of postoperative Irinotecan and Cisplatin chemotherapy followed by chemoradiation (Capecitabine-based) is an effective and safe regimen with moderate toxicity for patients with resected adenocarcinoma of the stomach. 1068 poster
1066 poster PALLIATIVE RADIOTHERAPY INSTEAD OF SURGERY IN SYMPTOMATIC RECTAL CANCER WITH SYNCHRONOUS UNRESECTABLE METASTASES D. Tyc-Szczepaniak1 , L. Wyrwicz2 , M. Olszyna-Serementa1 , L. Pietrzak1 , J. ´ 2 , A. Rutkowski2 , K. Bujko1 Krynski 1 M ARIA S KLODOWSKA -C URIE M EMORIAL C ANCER C ENTRE, Department of Radiotherapy, Warsaw, Poland 2 M ARIA S KLODOWSKA -C URIE M EMORIAL C ANCER C ENTRE, Department of Gastrointestinal Cancer, Warsaw, Poland Purpose: Apart from chemotherapy, palliative primary tumour resection or diverting stoma creation is currently a standard method of management for patients with symptomatic rectal cancer and nonresectable synchronous distant metastases. The potential advantage of using conservative treatment over surgery is to avoid stoma and postoperative complications. In the frame of a prospective study, we aim to answer the question as to whether surgery can be avoided by using short-course pelvic irradiation and immediate consolidation chemotherapy. Materials: Patients with symptomatic mid and low-lying rectal cancer and unresectable distant metastases received 5 x 5 Gy to the pelvis and oxaliplatinebased chemotherapy after one week. Planning target volume included only gross tumour with a margin. The effectiveness of local treatment was assessed by the self-administered questionnaires filled out by patients. Results: All twenty-one consecutive patients (planned sample size) who fulfilled the entry criteria were enrolled into our study between December 2009 and September 2010. Tumour obstructive symptoms were most frequently reported (62%). One month after radiotherapy, 38% of patients reported complete relief from pelvic symptoms, 57% reduction of symptom’s intensity and 5% (one patient) had stoma creation. At the last follow-up, two patients (10%) had stoma. The remaining 19 patients (90%) did not need surgery during follow-up which ranged from 1 to 9 months; with the median of 6 months. In the last questionnaire, 37% of these patients reported complete relief from pelvic symptoms, 47% partial response and 16% improvement with consecutive progression of symptoms but without a need for surgery. Seven patients died within 1 to 8 months (median 3) post radiation. Of these, six patients had their pelvic symptom controlled and did not require surgery and one patient had a stoma. Updated results will be presented at the conference. Conclusions: For symptomatic rectal cancer patients with unresectable distant metastases, pelvic radiation with consolidation chemotherapy represents a promising approach. 1067 poster POSTOPERATIVE IRINOTECAN/CISPLATIN CHEMOTHERAPY FOLLOWED BY CHEMORADIATION FOR STAGE IB-IIIB GASTRIC CANCER. E. Diamantidou1 , L. Vini2 , D. Hourmouzi3 , C. Kakana4 , A. Silyvridou5 1 I NTERBALKAN M EDICAL C ENTER, Medical Oncology, Thessaloniki, Greece 2 ATHENS M EDICAL C ENTRE, Radiation Oncology, Athens, Greece 3 I NTERBALKAN M EDICAL C ENTER, Radiology, Thessaloniki, Greece 4 I NTERBALKAN M EDICAL C ENTER, Medical Physics, Thessaloniki, Greece 5 ATHENS M EDICAL C ENTRE, Medical Physics, Athens, Greece Purpose: The aim of this prospective study was to evaluate toxicity and efficacy of postoperative adjuvant sequential Irinotecan and Cisplatin
PREOPERATIVE CAPECITABINE, RADIATION AND BEVACIZUMAB IN RECTAL CANCER: FINAL RESULTS OF THE CRAB PHASE II TRIAL V. Velenik1 , J. Ocvirk2 , M. Music3 , M. Bracko4 , F. Anderluh1 , I. Oblak1 , I. Edhemovic5 , E. Brecelj5 , M. Kropivnik3 , M. Omejc6 1 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Radiation Oncology, Ljubljana, Slovenia 2 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Medical Oncology, Ljubljana, Slovenia 3 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Radiology, Ljubljana, Slovenia 4 U NIVERSITY MEDICAL CENTER, Department of Pathology 5 I NSTITUTE OF O NCOLOGY L JUBLJANA, Department of Surgery, Ljubljana, Slovenia 6 U NIVERSITY MEDICAL CENTER, Department of Surgery Purpose: We assessed the efficacy and safety of adding bevacizumab (Bev) to standard, capecitabine-based neoadjuvant radiochemotherapy (CRT) to increase the pathological remission rate of locally advanced rectal cancer as primary end point. Materials: Enrolled patients (pts) with MRI-confirmed stage II/III rectal cancer were treated with an infusion of Bev (5 mg/kg) 2 weeks prior to neoadjuvant CRT, followed by Bev 5 mg/kg on week 3, 5, 7 and capecitabine 825 mg/m2 bid including weekends during RT. RT was administred at 50.4 Gy (25x1.8 Gy with boost 3x1.8 Gy, 3d conformal technique), starting on week 3. Total mesorectal excision was scheduled 6-8 weeks after completition of CRT. Tumor regression grades (TRG) were evaluated on surgical specimens according to Dworak. The primary endpoint was complete pathological response (pCR; TRG 4). Results: A total of 60 pts were eligible for analysis. Median age was 60 (range: 31-79) years, 64% of pts were male. Three pts presented with stage T2 (4.9%), 53 with stage T3 (86.9%), 5 with stage T4 (8.2%), and lymph node involvement was detected in 49 pts (80.3%). In 28 pts (45.9%) tumor invaded the mesorectal fascia. The median tumor distance from anal verge was 6 (range: 0-11) cm.Dose eduction or treatment interruption was required for 7 pts (11.6%) due to grade 2 (n=2) and grade 3 (n=2) leukopenia, grade 3 diarrhea (n=1), grade 3 (n=1) and grade 4 (n=1) vascular toxicity. Other grade 3 toxicities included dermatitis (n=6), proteinuria (n=4) and hypertension (n=1). Treatment was terminated in 1 pt due to withdrawal of the informed consent.Radical resection was achieved in 57 pts (95%) and 42 pts (70%) had sphincter preserving surgery. TRG 4 (pCR) was recorded in 8 pts (13.3%) and TRG 3 in 9 pts (15%). T-, N- and overall downstaging rates were 46.7%, 65% and 75%, respectively.Thirty-eight pts (62.3%) developed perioperative complications, most common delayed wound healing (n=18, 30%), infection/abscess (n=12, 20%) and anastomotic leak (n=7, 11.7%). Six pts required surgical reintervention for leak (n=3), abdominal abscess (n=2) and pneumothorax (n=1).Fifty pts (83.3%) received postoperative chemotherapy. Conclusions: The addition of Bev to standad capecitabine-based preoperative CRT is feasible and well tolerated. The high rate of radical resections suggests its potential effect on tumor downstaging. However, it is associated with considerable toxicity and with no clinically relevant increase in pCR rate. Longer follow-up is needed to assess the impact on other efficacy endpoints.