- Email: [email protected]
1065 poster P53 AS PREDICTIVE BIOMARKER IN LOCALLY ADVANCED RECTAL CANCER TREATED WITH PREOPERATIVE CHEMORADIOTHERAPY
S 396
R ECTAL CANCER
1062 poster NEOADJUVANT CHEMORADIATION IN LOCALLY ADVANCED RECTAL CANCER P. Meireles1 , D. Fonte1 , A. Costa2 , D. Almeida2 , M. Reis Lima Marques1 , C. Sarmento2 , C. Rey2 , G. Pinto1 1 H OSPITAL DE S ÃO J OÃO, Department of Radiation Oncology, Porto, Portugal 2 H OSPITAL DE S ÃO J OÃO, Department of Medical Oncology, Porto, Portugal Purpose: Neoadjuvant combined therapy has become the standard of care in Locally Advanced Rectal Cancer. This approach has demonstrated improved local control rates, pathological complete response and downstage of locally advanced disease preoperatively. The endpoints of this study were downstaging and pathological complete response. Materials: We retrospectively evaluated 140 patients that received neoadjuvant chemoradiation for locally advanced rectal cancer between January 2003 and June 2010. Ten cases were excluded from this analysis due to the lack of information regarding the chemotherapy regimen used. RT dose ranged from 45 Gy in 25 fractions to 50,4 in 28 fractions. The most recent patients received 50 Gy in 25 fractions. Concurrent chemotherapy was either 5-FU based or with capecitabine. Surgery was performed 6-8 weeks after the end of neoadjuvancy. Results: The median age at diagnosis was 63 years with a minimum of 34 and a maximum of 83 years. There was a male predominance (63,1%) in the study population. Regarding location 9,2% of the cases where in the upper third of the rectum, 38,5% in the middle third and 52,3% in the lower third. According to clinical staging, 33,8% of the cases were in stage IIa, 4,6% in stage IIb, 60,8% in stage IIIb and 0,8% in stage IIIc. All patients received chemoradiation. The chemotherapy regimen was 5-FU based in 60,8% of the patients and capecitabine in 39,6%. The radiotherapy fractionation was either 1,8 or 2 Gy/daily fraction, with a total dose that ranged from 45 Gy to 50,4 Gy for the patients with a 1,8 Gy/daily fraction and 46 to 50 Gy for patients with a 2 Gy/daily fraction. One patient had to stop treatment with a total dose of 36 Gy due to hematologic toxicity. Surgery was performed in 129 patients and 1 patient refused. Of those 129 patients 41,1% had an abdominoperineal ressection, 52,7% a low anterior ressection and in 6,2% was nonresectable. There was downstaging after neoadjuvante chemoradiation in 61,2% of cases. In 13,2% (17 patients) there was a pathological complete response (pCR) after neoadjuvant chemoradiation. Conclusions: Neoadjuvant chemoradiation with 5-FU or capecitabine allows pCR and downstaging. These results are similar to those published in the literature 1063 poster NEOADJUVANT VOLUMETRIC MODULATED ARC THERAPY FOR RECTAL CANCER: ANALYSIS OF ACUTE TOXICITY DATA OF 16 PATIENTS A. Cecconi1 , P. Porcu2 , M. C. Leonardi1 , R. Lazzari1 , B. A. JereczekFossa1 3 , A. Vavassori1 , R. Mauro1 3 , E. Rondi4 , S. Vigorito4 , F. Cattani4 , C. Fodor1 , R. Orecchia1 3 1 E UROPEAN I NSTITUTE OF O NCOLOGY, Division of Radiotherapy, Milan, Italy 2 F ONDAZIONE S ALVATORE M AUGERI, Division of Radiotherapy, Pavia, Italy 3 U NIVERSITY OF M ILAN, Milan, Italy 4 E UROPEAN I NSTITUTE OF O NCOLOGY, Division of Medical Physics, Milan, Italy Purpose: Pre-operative chemo-radiotherapy (CT-RT) of rectal cancer (RC) in locally advance stage has become a widely accepted treatment modality. Aim of the present study is to evaluate feasibility and acute toxicity in a series of 16 patients (pts) treated with neoadjuvant volumetric intensity modulated arc therapy with RapidArc (RA-IMRT) for RC. Materials: From February to October 2010 16 pts affected by locally advanced RC were treated with neoadjuvant RA-IMRT. 11 pts were male and 5 pts were female, median age was 63 years. The T stage distribution was as follows: T2, T3 and T4 in 2 pts (12.5%) in 13 pts (81.5%) and in 1 pts (6.25%), respectively. The N stage distribution was as followes: N0, N1 and N2 in 3 pts (18.7%), 9 pts (56.2%) and 4 (25%), respectively. 3 pts had proximal, 3 pts had medium-distal and 9 distal(RC).In all pts concomitant chemotherapy with oral capecitabine schedule was added to RA-IMRT. All pts underwent a 3 mm slicing simulation/treatment planning CT scan from diaphragm to lesser trochanter.Clinical target volume (CTV) of the primary tumor was created by addition of 10 mm to GTV. Margins of 5/10mm and 5 mm were added to create PTV-T (planning target volume) and PTV-N from CTV-T and CTV-N, respectively.Dose prescription was set according to simultaneous integrated boost (SIB) strategy to 55 Gy to the primary tumor and positive lymph nodes (N) (at 2.2Gy/fraction) and to 45 Gy (at 1.8 Gy/fraction) to N risk area including presacral, internal and external iliac and obturator N. Before treatment all pts were seen by radiation oncologist. During RA-IMAT patients were visited twice a week, and then at the end of treatment.The RTOG/EORTC criteria were used to evaluate the acute genito-urinary (GU), the gastro-intestinal (GI) and the skin toxicity (SKT).
Results: Before treatment all pts had a Karnofsky performance status (KPS) 100 and 2 pts complained about pain, 9 pts bleeding, 4 pts constipation, 1 pt abdominal distension, 2 pts diarrhea, and 4 pt had diarrhea or constipation alternately. 15 out of 16 pts have now completed treatment without any interruption. 1 pt stopped treatment for "metabolic syndrome X" (36 Gy). Acute toxicity at the end of RA-IMRT included GI (G0: 4 pts; G1: 5 pts, G2:6 pts); GU (G0: 7 pts, G1: 4 pts; G2:4 pts); and SKT (G0:7 pts, G1: 7 pts, G2:1 pts). Conclusions: Our preliminary experience showed that RA-IMAT is a highly tolerable treatment modality with low GU, GI and SKT, as demonstrated by the complete absence of toxicity G3 at the end of treatment despite dose escalation and SIB.Further investigation with higher patient number and longer follow-up is warranted in order to verify if low acute toxicity observed in our preliminary analysis is translated to low late toxicity and satisfactory tumour control. 1064 poster ON THE DEVELOPMENT AND CLINICAL IMPLEMENTATION OF AN INCLINED BELLY BOARD FOR CONSISTENT SMALL BOWEL DISPLACEMENT V. Kundapur1 , G. Cranmer-Sargison2 , H. Vachhrajani1 , N. Sidhu2 1 S ASKATOON C ANCER C ENTRE, Radiation Oncology, Saskatoon, Saskatchewan, Canada 2 S ASKATOON C ANCER C ENTRE, Department of Medical Physics and Radiation Safety, Saskatoon, Saskatchewan, Canada
Purpose: Excluding small bowel (SB) during pelvic radiation is challenging. Techniques and devices reported on in the literature are varied. To date, very little data has been published on the true SB displacement during treatment and no published work on the reproducibility in SB displacement. We have developed an inclined belly board (iBB) that is ergonomic, ensures stable patient set up and provides reproducible small bowel displacement. We validate the reproducibility in SB displacement during treatment using CBCT. Materials: An initial 49 patients were treated on an iBB constructed in-house. Patient set-up, comfort and small bowel displacement were all assessed and from our recommendations a commercial iBB produced by CDR System Inc. A total of 69 patients have now been treated on the commercial iBB. Patient treatment position, as well as the consistency in small bowel displacement, has been quantitatively and qualitatively assessed for 24 of the 69 patients using CBCT data. At treatment, a set of kV-kV images were taken daily, a bony anatomy match performed and subsequent couch moves made along each axis. CBCT data was acquired once every 5 fractions (weekly) for a total of 5 images per patient. A 3D-3D bony anatomy auto-match was performed offline and the residual difference in position recoded for analysis. A Likert response scale questionnaire was used to assess the quality in small bowel displacement (CT data) and the consistency of the displacement over the course of treatment (CBCT data). The evaluations were conducted on 12 of the 24 patients by 2 ROs blinded for patient information. A quality assurance (QA) program has been developed for the routine use of the iBB to ensure consistent small bowel displacement and patient setup while irradiating malignant tumours in the pelvis. Results: The average residual difference in patient position calculated using the bony anatomy auto-match was AP = -1.07 ± 2.25 mm, SI = 0.85 ± 1.45 mm and LR = -0.07 ± 1.11 mm. The grading associated with the normalized Likert response scores for SB displacement and consistency in SB displacement were as follows: moderate (0.4 to 0.6), good (0.6 to 0.8) and excellent (0.8 to 1.0). The average scores taken over the 12 data sets were 0.72 (displacement) and 0.73 (consistency) for RO1 and 0.79 and 0.83 for RO2. Using the findings of this investigation we developed a QA program for using the iBB which encompasses the initial patient set-up at CT simulation, isocenter selection, treatment set-up as well as CBCT acquisition frequency. These details will be presented. Conclusions: Our work resulted in the development of an ergonomically iBB which provides robust patient set-up resulting in satisfactory displacement of the small bowel for rectal cancer patients during radiation treatment 1065 poster P53 AS PREDICTIVE BIOMARKER IN LOCALLY ADVANCED RECTAL CANCER TREATED WITH PREOPERATIVE CHEMORADIOTHERAPY S. Stojanovic-Rundic1 , M. Micev2 , I. Popov3 , Z. Krivokapic4 , D. Gavrilovic5 1
I NSTITUTE FOR O NCOLOGY AND R ADIOLOGY OF S ERBIA, Radiotherapy, Belgrade, Serbia I NSTITUTE FOR D IGESTIVE D ISEASE , C LINICAL C ENTER OF S ERBIA, Pathology, Belgrade, Serbia 3 I NSTITUTE FOR O NCOLOGY AND R ADIOLOGY OF S ERBIA, Medical Oncology, Belgrade, Serbia 4 I NSTITUTE FOR D IGESTIVE D ISEASE , C LINICAL C ENTER OF S ERBIA, Surgery, Belgrade, Serbia 5 I NSTITUTE FOR O NCOLOGY AND R ADIOLOGY OF S ERBIA, Data Centre, Belgrade, Serbia 2
Purpose: This study was performed to investigate correlation between value
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.
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.
R ECTAL CANCER
1062 poster NEOADJUVANT CHEMORADIATION IN LOCALLY ADVANCED RECTAL CANCER P. Meireles1 , D. Fonte1 , A. Costa2 , D. Almeida2 , M. Reis Lima Marques1 , C. Sarmento2 , C. Rey2 , G. Pinto1 1 H OSPITAL DE S ÃO J OÃO, Department of Radiation Oncology, Porto, Portugal 2 H OSPITAL DE S ÃO J OÃO, Department of Medical Oncology, Porto, Portugal Purpose: Neoadjuvant combined therapy has become the standard of care in Locally Advanced Rectal Cancer. This approach has demonstrated improved local control rates, pathological complete response and downstage of locally advanced disease preoperatively. The endpoints of this study were downstaging and pathological complete response. Materials: We retrospectively evaluated 140 patients that received neoadjuvant chemoradiation for locally advanced rectal cancer between January 2003 and June 2010. Ten cases were excluded from this analysis due to the lack of information regarding the chemotherapy regimen used. RT dose ranged from 45 Gy in 25 fractions to 50,4 in 28 fractions. The most recent patients received 50 Gy in 25 fractions. Concurrent chemotherapy was either 5-FU based or with capecitabine. Surgery was performed 6-8 weeks after the end of neoadjuvancy. Results: The median age at diagnosis was 63 years with a minimum of 34 and a maximum of 83 years. There was a male predominance (63,1%) in the study population. Regarding location 9,2% of the cases where in the upper third of the rectum, 38,5% in the middle third and 52,3% in the lower third. According to clinical staging, 33,8% of the cases were in stage IIa, 4,6% in stage IIb, 60,8% in stage IIIb and 0,8% in stage IIIc. All patients received chemoradiation. The chemotherapy regimen was 5-FU based in 60,8% of the patients and capecitabine in 39,6%. The radiotherapy fractionation was either 1,8 or 2 Gy/daily fraction, with a total dose that ranged from 45 Gy to 50,4 Gy for the patients with a 1,8 Gy/daily fraction and 46 to 50 Gy for patients with a 2 Gy/daily fraction. One patient had to stop treatment with a total dose of 36 Gy due to hematologic toxicity. Surgery was performed in 129 patients and 1 patient refused. Of those 129 patients 41,1% had an abdominoperineal ressection, 52,7% a low anterior ressection and in 6,2% was nonresectable. There was downstaging after neoadjuvante chemoradiation in 61,2% of cases. In 13,2% (17 patients) there was a pathological complete response (pCR) after neoadjuvant chemoradiation. Conclusions: Neoadjuvant chemoradiation with 5-FU or capecitabine allows pCR and downstaging. These results are similar to those published in the literature 1063 poster NEOADJUVANT VOLUMETRIC MODULATED ARC THERAPY FOR RECTAL CANCER: ANALYSIS OF ACUTE TOXICITY DATA OF 16 PATIENTS A. Cecconi1 , P. Porcu2 , M. C. Leonardi1 , R. Lazzari1 , B. A. JereczekFossa1 3 , A. Vavassori1 , R. Mauro1 3 , E. Rondi4 , S. Vigorito4 , F. Cattani4 , C. Fodor1 , R. Orecchia1 3 1 E UROPEAN I NSTITUTE OF O NCOLOGY, Division of Radiotherapy, Milan, Italy 2 F ONDAZIONE S ALVATORE M AUGERI, Division of Radiotherapy, Pavia, Italy 3 U NIVERSITY OF M ILAN, Milan, Italy 4 E UROPEAN I NSTITUTE OF O NCOLOGY, Division of Medical Physics, Milan, Italy Purpose: Pre-operative chemo-radiotherapy (CT-RT) of rectal cancer (RC) in locally advance stage has become a widely accepted treatment modality. Aim of the present study is to evaluate feasibility and acute toxicity in a series of 16 patients (pts) treated with neoadjuvant volumetric intensity modulated arc therapy with RapidArc (RA-IMRT) for RC. Materials: From February to October 2010 16 pts affected by locally advanced RC were treated with neoadjuvant RA-IMRT. 11 pts were male and 5 pts were female, median age was 63 years. The T stage distribution was as follows: T2, T3 and T4 in 2 pts (12.5%) in 13 pts (81.5%) and in 1 pts (6.25%), respectively. The N stage distribution was as followes: N0, N1 and N2 in 3 pts (18.7%), 9 pts (56.2%) and 4 (25%), respectively. 3 pts had proximal, 3 pts had medium-distal and 9 distal(RC).In all pts concomitant chemotherapy with oral capecitabine schedule was added to RA-IMRT. All pts underwent a 3 mm slicing simulation/treatment planning CT scan from diaphragm to lesser trochanter.Clinical target volume (CTV) of the primary tumor was created by addition of 10 mm to GTV. Margins of 5/10mm and 5 mm were added to create PTV-T (planning target volume) and PTV-N from CTV-T and CTV-N, respectively.Dose prescription was set according to simultaneous integrated boost (SIB) strategy to 55 Gy to the primary tumor and positive lymph nodes (N) (at 2.2Gy/fraction) and to 45 Gy (at 1.8 Gy/fraction) to N risk area including presacral, internal and external iliac and obturator N. Before treatment all pts were seen by radiation oncologist. During RA-IMAT patients were visited twice a week, and then at the end of treatment.The RTOG/EORTC criteria were used to evaluate the acute genito-urinary (GU), the gastro-intestinal (GI) and the skin toxicity (SKT).
Results: Before treatment all pts had a Karnofsky performance status (KPS) 100 and 2 pts complained about pain, 9 pts bleeding, 4 pts constipation, 1 pt abdominal distension, 2 pts diarrhea, and 4 pt had diarrhea or constipation alternately. 15 out of 16 pts have now completed treatment without any interruption. 1 pt stopped treatment for "metabolic syndrome X" (36 Gy). Acute toxicity at the end of RA-IMRT included GI (G0: 4 pts; G1: 5 pts, G2:6 pts); GU (G0: 7 pts, G1: 4 pts; G2:4 pts); and SKT (G0:7 pts, G1: 7 pts, G2:1 pts). Conclusions: Our preliminary experience showed that RA-IMAT is a highly tolerable treatment modality with low GU, GI and SKT, as demonstrated by the complete absence of toxicity G3 at the end of treatment despite dose escalation and SIB.Further investigation with higher patient number and longer follow-up is warranted in order to verify if low acute toxicity observed in our preliminary analysis is translated to low late toxicity and satisfactory tumour control. 1064 poster ON THE DEVELOPMENT AND CLINICAL IMPLEMENTATION OF AN INCLINED BELLY BOARD FOR CONSISTENT SMALL BOWEL DISPLACEMENT V. Kundapur1 , G. Cranmer-Sargison2 , H. Vachhrajani1 , N. Sidhu2 1 S ASKATOON C ANCER C ENTRE, Radiation Oncology, Saskatoon, Saskatchewan, Canada 2 S ASKATOON C ANCER C ENTRE, Department of Medical Physics and Radiation Safety, Saskatoon, Saskatchewan, Canada
Purpose: Excluding small bowel (SB) during pelvic radiation is challenging. Techniques and devices reported on in the literature are varied. To date, very little data has been published on the true SB displacement during treatment and no published work on the reproducibility in SB displacement. We have developed an inclined belly board (iBB) that is ergonomic, ensures stable patient set up and provides reproducible small bowel displacement. We validate the reproducibility in SB displacement during treatment using CBCT. Materials: An initial 49 patients were treated on an iBB constructed in-house. Patient set-up, comfort and small bowel displacement were all assessed and from our recommendations a commercial iBB produced by CDR System Inc. A total of 69 patients have now been treated on the commercial iBB. Patient treatment position, as well as the consistency in small bowel displacement, has been quantitatively and qualitatively assessed for 24 of the 69 patients using CBCT data. At treatment, a set of kV-kV images were taken daily, a bony anatomy match performed and subsequent couch moves made along each axis. CBCT data was acquired once every 5 fractions (weekly) for a total of 5 images per patient. A 3D-3D bony anatomy auto-match was performed offline and the residual difference in position recoded for analysis. A Likert response scale questionnaire was used to assess the quality in small bowel displacement (CT data) and the consistency of the displacement over the course of treatment (CBCT data). The evaluations were conducted on 12 of the 24 patients by 2 ROs blinded for patient information. A quality assurance (QA) program has been developed for the routine use of the iBB to ensure consistent small bowel displacement and patient setup while irradiating malignant tumours in the pelvis. Results: The average residual difference in patient position calculated using the bony anatomy auto-match was AP = -1.07 ± 2.25 mm, SI = 0.85 ± 1.45 mm and LR = -0.07 ± 1.11 mm. The grading associated with the normalized Likert response scores for SB displacement and consistency in SB displacement were as follows: moderate (0.4 to 0.6), good (0.6 to 0.8) and excellent (0.8 to 1.0). The average scores taken over the 12 data sets were 0.72 (displacement) and 0.73 (consistency) for RO1 and 0.79 and 0.83 for RO2. Using the findings of this investigation we developed a QA program for using the iBB which encompasses the initial patient set-up at CT simulation, isocenter selection, treatment set-up as well as CBCT acquisition frequency. These details will be presented. Conclusions: Our work resulted in the development of an ergonomically iBB which provides robust patient set-up resulting in satisfactory displacement of the small bowel for rectal cancer patients during radiation treatment 1065 poster P53 AS PREDICTIVE BIOMARKER IN LOCALLY ADVANCED RECTAL CANCER TREATED WITH PREOPERATIVE CHEMORADIOTHERAPY S. Stojanovic-Rundic1 , M. Micev2 , I. Popov3 , Z. Krivokapic4 , D. Gavrilovic5 1
I NSTITUTE FOR O NCOLOGY AND R ADIOLOGY OF S ERBIA, Radiotherapy, Belgrade, Serbia I NSTITUTE FOR D IGESTIVE D ISEASE , C LINICAL C ENTER OF S ERBIA, Pathology, Belgrade, Serbia 3 I NSTITUTE FOR O NCOLOGY AND R ADIOLOGY OF S ERBIA, Medical Oncology, Belgrade, Serbia 4 I NSTITUTE FOR D IGESTIVE D ISEASE , C LINICAL C ENTER OF S ERBIA, Surgery, Belgrade, Serbia 5 I NSTITUTE FOR O NCOLOGY AND R ADIOLOGY OF S ERBIA, Data Centre, Belgrade, Serbia 2
Purpose: This study was performed to investigate correlation between value
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.
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.