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EP-1081 LOCO-REGIONAL CONTROL AFTER RADIOCHEMOTHERAPY FOR ANAL CANCER: A SINGLE CENTRE RETROSPECTIVE ANALYSIS
ESTRO 31
chemoradiation (CCRT) using Helical Tomotherapy (HT) based Intensity Modulated and Image Guided Radiotherapy with radiation dose escalation and simultaneous integrated boost to gross disease. All patients underwent PET CT scan to rule out metastatic disease prior to starting chemoradiation and 6 weeks post chemoradiation to evaluate response. These patients were then planned for concomitant chemoradiation using Tomotherapy based IMRT to a doses of 57-60 Gy over 25 fractions to the gross tumour as a simultaneous integrated boost volume and 45-50 Gy to the surrounding tissues and the grossly uninvolved draining nodes. While planning special care was taken so that the dose to duodenum was restricted to 50% of the volume to receive less than 45 Gy. The patients underwent daily MVCT imaging co registration prior to RT. All the patients received concurrent chemotherapy with Inj. Gemcitabine (weekly 300mg/m2). Results: Of the 17 patients 1 patient could not complete RT due to repeated cholangitis during treatment and 1 developed liver metastasis during radiotherapy. Rest of the 15 patients could complete planned treatment. No patient developed acute grade 3 GI toxicity. Of these 8/17 (47%) underwent R0 resection. Rest either developed progressive disease or had metastatic disease during surgical exploration. Conclusions: Locally advanced gall bladder cancers not amenable to upfront surgical resection can be down staged by neoadjuvant chemoradiation to undergo curative surgical resection in almost 50% of the patients. EP-1080 FDG-PET SUV AND BIOLOGICAL MARKERS AS PREDICTIVE FACTORS OF TUMOUR RESPONSE IN ANAL CANAL CANCER TREATED WITH RT-CT M. Krengli1, M.E. Milia1, L. Deantonio1, L. Turri1, G. Loi2, G. Sacchetti3, R. Boldorini4, E. Maldi4, T. Cena5, C. Magnani5 1 University Hospital "Maggiore della Carità", Radiotherapy, Novara, Italy 2 University Hospital "Maggiore della Carità", Medical Physics, Novara, Italy 3 University Hospital "Maggiore della Carità", Nuclear Medicine, Novara, Italy 4 University Hospital "Maggiore della Carità", Phatology, Novara, Italy 5 University Hospital "Maggiore della Carità", Epidemiology and Biostatistics, Novara, Italy Purpose/Objective: PET/CT has an emerging role in management of anal cancer. FDG-PET standard uptake value (SUV) and molecular biomarkers have been identified as prognostic factors. The present study analyzed the role of SUV and biological markers as potential predictors of tumour response in a series of anal canal cancer patients treated with radio-chemotherapy (RT-CT). Materials and Methods: Forty-seven patients (pts), 17 male and 30 female, with a mean age of 67 years (range 40-95), with biopsy proven anal carcinoma and treated with RT-CT were included in the present analysis. Histology was squamous cell in 35/47 pts (75%), cloacogenic in 9/47 (19%) and adenocarcinoma in 3/47 (6%). Clinical stage according to TNM was: 3 T1, 18 T2, 22 T3 and 4 T4. Nineteen patients had lymph node involvement at presentation: 1 N1, 12 N2 and 6 N3. PET/CT for staging and simulation was performed in 41/47 pts (87%). Maximum (max) and average (avg) SUV was calculated for each patient. In 20/47 (43%) pts, KRAS, BRAF, EGFR and Ki67 expression and mutations were also analyzed. Forty of 47 pts (85%) received chemo-RT and 7 pts radiotherapy alone. Chemotherapy consisted of mytomicin C and 5-fluorouracil (FU) in 19/40 pts (48%) or cisplatin and 5-FU in 21/40 pts (52%). Response was evaluated by clinical examination, endoscopy, CT-scan and biopsy 2-4 months after end of chemo-RT. IMRT was delivered in 8/47 pts and 3D-conformal in 39/47. Dose ranged from 54 to 65 Gy to tumour target (median 59.4 Gy) and from 39.6 Gy to 45 Gy to the uninvolved lymph nodes (median 45 Gy) with 1.8 Gy/fx/daily. Results: We observed 22/47 (47%) complete response (CR), 23/47 (49%) partial response (PR) and 2/47 (4%) no response. SUVmax and SUVavg significantly correlated with T-stage (p=0.02 and p=0.01) and with clinical response (p=0.0023 and p=0.0291). Histology significantly influenced SUVavg. No significant correlation was found between SUV, grading and increased risk of N+. Higher SUVmax of the primary tumour was associated with a significant worse disease-free survival by LogRank Test (p=0.01). All pts were wild-type BRAF and 3 mutations of KRAS were observed. Two pts had high polysomy of EGFR. We did not find a correlation between EGFR amplification, KRAS mutations and treatment response.
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Conclusions: SUVmax and SUVavg were associated with response to CRT. Our results are in accord with those of the literature and confirm the negative predictive value of SUVmax and SUVavg and their association with a poor DFS. No correlation was found between biological markers and response. EP-1081 LOCO-REGIONAL CONTROL AFTER RADIOCHEMOTHERAPY FOR ANAL CANCER: A SINGLE CENTRE RETROSPECTIVE ANALYSIS F. Zehentmayr1, M.C. Wolf1, M.E. Kreis2, C. Belka1 1 Ludwig-Maximilian-University, Academic Department of Radiation Oncology, Munich, Germany 2 Ludwig-Maximilian-University, Academic Department of Surgery, Munich, Germany Purpose/Objective: To evaluate long term loco-regional control- and survival rates after radical radiochemotherapy for anal cancer in nonselected patients treated outside of controlled trials a retrospective analysis was performed. Materials and Methods: Between 07/2002 and 12/2010 109 consecutive patients with anal cancer were identified from the institutional data base. Chart review, data from the Munich Cancer Registry (MCR) and telephone follow up were undertaken to collect data. Results: 109 (69 female / 40 male) patients who received radiochemotherapy for anal cancer in a curative intention were identified. The median age at diagnosis was 63y (range 28-93). The disease stages (UICC 7th ed., 2010) were distributed as follows: 2/109 (1.8%) UICC 0, 19/109 (17.4%) UICC I, 47/109 (43.1%) UICC II, 23/109 (21.1%) UICC III and 4/109 (3.7%) UICC IV, 14/109 (12.8%) were unknown. 25/109 (22.9%) patients had tumours located at the anal verge, in 56/109 (51.4%) patients the tumour was located in the anal canal itself and in 26/109 (23.9%) patients it extended to the ampulla recti. The median dose to the primary tumour was 59.4 Gy (45 - 64.8 Gy). 99/109 (90.8%) received concomitant chemotherapy, 70/109 (64.2%) with MMC/5-FU, 13/109 (11.9%) with 5-FU mono, 4/109 (3.7) with MMC mono, 2/109 (1.8) platin based, 5/109 (4.6%) did not receive chemotherapy due to relevant co-morbidities and for 10/109 (9.2%) it was not possible to determine whether they received concomitant chemotherapy or not. Loco-regional control was defined as freedom from relapse of the primary or lymphnode of the pelvis and the groins. With a median follow-up (period from diagnosis until last follow up / death) of 36 months (mean 45 months) the local control rates were 97% at 1y, 95% at 2y, 93% at 3y, 92% at 5y, 82% at 10y; disease free survival is 88% at 2y, 84% at 3y, 80% at 4y, 74% at 5y. The addition of chemotherapy significantly improves loco-regional control (p=0.015). Conclusions: Although radiochemotherapy with MMC/5FU is a highly effective therapy for anal cancer, response rates might be further improved by individualised approaches. EP-1082 ROLE OF PRETREATMENT CEA LEVEL IN PATIENTS WITH RECTAL CANCER RECEIVING PREOPERATIVE CHEMORADIOTHERAPY S. Yeo1, D. Kim2 1 Soonchunhyang University College of Medicine, Department of Radiation Oncology, Cheonan, Korea Republic of 2 National Cancer Center, Center for Colorectal Cancer, Goyang, Korea Republic of Purpose/Objective: The pretreatment serum carcinoembryonic antigen (CEA) level is an independent prognostic factor in colorectal cancer. However, few studies have evaluated its prognostic significance after preoperative chemoradiotherapy (CRT), which has become widely adopted in patients with rectal cancer. Here, the significance of the CEA as a prognostic or predictive factor was investigated. Materials and Methods: In total, 609 patients with locally advanced (cStage II–III) mid to distal rectal cancer who underwent preoperative CRT and radical surgery between 2001 and 2008 were analyzed retrospectively. A prognostic factor analysis was performed using the log-rank test and Cox proportional hazards regression. Predictive factors for pathologic CRT response were determined using multivariate logistic regression. Results: Elevated CEA levels (> 5 ng/mL) were observed in 201 (33.0%) patients at diagnosis. Following preoperative CRT, a downstaging (ypStage 0–I) occurred in 255 (41.9%) patients, of whom 88 had pathologic complete tumor regression. The median follow-up period was 60 months, and the 5-year disease-free and overall survival rates
chemoradiation (CCRT) using Helical Tomotherapy (HT) based Intensity Modulated and Image Guided Radiotherapy with radiation dose escalation and simultaneous integrated boost to gross disease. All patients underwent PET CT scan to rule out metastatic disease prior to starting chemoradiation and 6 weeks post chemoradiation to evaluate response. These patients were then planned for concomitant chemoradiation using Tomotherapy based IMRT to a doses of 57-60 Gy over 25 fractions to the gross tumour as a simultaneous integrated boost volume and 45-50 Gy to the surrounding tissues and the grossly uninvolved draining nodes. While planning special care was taken so that the dose to duodenum was restricted to 50% of the volume to receive less than 45 Gy. The patients underwent daily MVCT imaging co registration prior to RT. All the patients received concurrent chemotherapy with Inj. Gemcitabine (weekly 300mg/m2). Results: Of the 17 patients 1 patient could not complete RT due to repeated cholangitis during treatment and 1 developed liver metastasis during radiotherapy. Rest of the 15 patients could complete planned treatment. No patient developed acute grade 3 GI toxicity. Of these 8/17 (47%) underwent R0 resection. Rest either developed progressive disease or had metastatic disease during surgical exploration. Conclusions: Locally advanced gall bladder cancers not amenable to upfront surgical resection can be down staged by neoadjuvant chemoradiation to undergo curative surgical resection in almost 50% of the patients. EP-1080 FDG-PET SUV AND BIOLOGICAL MARKERS AS PREDICTIVE FACTORS OF TUMOUR RESPONSE IN ANAL CANAL CANCER TREATED WITH RT-CT M. Krengli1, M.E. Milia1, L. Deantonio1, L. Turri1, G. Loi2, G. Sacchetti3, R. Boldorini4, E. Maldi4, T. Cena5, C. Magnani5 1 University Hospital "Maggiore della Carità", Radiotherapy, Novara, Italy 2 University Hospital "Maggiore della Carità", Medical Physics, Novara, Italy 3 University Hospital "Maggiore della Carità", Nuclear Medicine, Novara, Italy 4 University Hospital "Maggiore della Carità", Phatology, Novara, Italy 5 University Hospital "Maggiore della Carità", Epidemiology and Biostatistics, Novara, Italy Purpose/Objective: PET/CT has an emerging role in management of anal cancer. FDG-PET standard uptake value (SUV) and molecular biomarkers have been identified as prognostic factors. The present study analyzed the role of SUV and biological markers as potential predictors of tumour response in a series of anal canal cancer patients treated with radio-chemotherapy (RT-CT). Materials and Methods: Forty-seven patients (pts), 17 male and 30 female, with a mean age of 67 years (range 40-95), with biopsy proven anal carcinoma and treated with RT-CT were included in the present analysis. Histology was squamous cell in 35/47 pts (75%), cloacogenic in 9/47 (19%) and adenocarcinoma in 3/47 (6%). Clinical stage according to TNM was: 3 T1, 18 T2, 22 T3 and 4 T4. Nineteen patients had lymph node involvement at presentation: 1 N1, 12 N2 and 6 N3. PET/CT for staging and simulation was performed in 41/47 pts (87%). Maximum (max) and average (avg) SUV was calculated for each patient. In 20/47 (43%) pts, KRAS, BRAF, EGFR and Ki67 expression and mutations were also analyzed. Forty of 47 pts (85%) received chemo-RT and 7 pts radiotherapy alone. Chemotherapy consisted of mytomicin C and 5-fluorouracil (FU) in 19/40 pts (48%) or cisplatin and 5-FU in 21/40 pts (52%). Response was evaluated by clinical examination, endoscopy, CT-scan and biopsy 2-4 months after end of chemo-RT. IMRT was delivered in 8/47 pts and 3D-conformal in 39/47. Dose ranged from 54 to 65 Gy to tumour target (median 59.4 Gy) and from 39.6 Gy to 45 Gy to the uninvolved lymph nodes (median 45 Gy) with 1.8 Gy/fx/daily. Results: We observed 22/47 (47%) complete response (CR), 23/47 (49%) partial response (PR) and 2/47 (4%) no response. SUVmax and SUVavg significantly correlated with T-stage (p=0.02 and p=0.01) and with clinical response (p=0.0023 and p=0.0291). Histology significantly influenced SUVavg. No significant correlation was found between SUV, grading and increased risk of N+. Higher SUVmax of the primary tumour was associated with a significant worse disease-free survival by LogRank Test (p=0.01). All pts were wild-type BRAF and 3 mutations of KRAS were observed. Two pts had high polysomy of EGFR. We did not find a correlation between EGFR amplification, KRAS mutations and treatment response.
S419
Conclusions: SUVmax and SUVavg were associated with response to CRT. Our results are in accord with those of the literature and confirm the negative predictive value of SUVmax and SUVavg and their association with a poor DFS. No correlation was found between biological markers and response. EP-1081 LOCO-REGIONAL CONTROL AFTER RADIOCHEMOTHERAPY FOR ANAL CANCER: A SINGLE CENTRE RETROSPECTIVE ANALYSIS F. Zehentmayr1, M.C. Wolf1, M.E. Kreis2, C. Belka1 1 Ludwig-Maximilian-University, Academic Department of Radiation Oncology, Munich, Germany 2 Ludwig-Maximilian-University, Academic Department of Surgery, Munich, Germany Purpose/Objective: To evaluate long term loco-regional control- and survival rates after radical radiochemotherapy for anal cancer in nonselected patients treated outside of controlled trials a retrospective analysis was performed. Materials and Methods: Between 07/2002 and 12/2010 109 consecutive patients with anal cancer were identified from the institutional data base. Chart review, data from the Munich Cancer Registry (MCR) and telephone follow up were undertaken to collect data. Results: 109 (69 female / 40 male) patients who received radiochemotherapy for anal cancer in a curative intention were identified. The median age at diagnosis was 63y (range 28-93). The disease stages (UICC 7th ed., 2010) were distributed as follows: 2/109 (1.8%) UICC 0, 19/109 (17.4%) UICC I, 47/109 (43.1%) UICC II, 23/109 (21.1%) UICC III and 4/109 (3.7%) UICC IV, 14/109 (12.8%) were unknown. 25/109 (22.9%) patients had tumours located at the anal verge, in 56/109 (51.4%) patients the tumour was located in the anal canal itself and in 26/109 (23.9%) patients it extended to the ampulla recti. The median dose to the primary tumour was 59.4 Gy (45 - 64.8 Gy). 99/109 (90.8%) received concomitant chemotherapy, 70/109 (64.2%) with MMC/5-FU, 13/109 (11.9%) with 5-FU mono, 4/109 (3.7) with MMC mono, 2/109 (1.8) platin based, 5/109 (4.6%) did not receive chemotherapy due to relevant co-morbidities and for 10/109 (9.2%) it was not possible to determine whether they received concomitant chemotherapy or not. Loco-regional control was defined as freedom from relapse of the primary or lymphnode of the pelvis and the groins. With a median follow-up (period from diagnosis until last follow up / death) of 36 months (mean 45 months) the local control rates were 97% at 1y, 95% at 2y, 93% at 3y, 92% at 5y, 82% at 10y; disease free survival is 88% at 2y, 84% at 3y, 80% at 4y, 74% at 5y. The addition of chemotherapy significantly improves loco-regional control (p=0.015). Conclusions: Although radiochemotherapy with MMC/5FU is a highly effective therapy for anal cancer, response rates might be further improved by individualised approaches. EP-1082 ROLE OF PRETREATMENT CEA LEVEL IN PATIENTS WITH RECTAL CANCER RECEIVING PREOPERATIVE CHEMORADIOTHERAPY S. Yeo1, D. Kim2 1 Soonchunhyang University College of Medicine, Department of Radiation Oncology, Cheonan, Korea Republic of 2 National Cancer Center, Center for Colorectal Cancer, Goyang, Korea Republic of Purpose/Objective: The pretreatment serum carcinoembryonic antigen (CEA) level is an independent prognostic factor in colorectal cancer. However, few studies have evaluated its prognostic significance after preoperative chemoradiotherapy (CRT), which has become widely adopted in patients with rectal cancer. Here, the significance of the CEA as a prognostic or predictive factor was investigated. Materials and Methods: In total, 609 patients with locally advanced (cStage II–III) mid to distal rectal cancer who underwent preoperative CRT and radical surgery between 2001 and 2008 were analyzed retrospectively. A prognostic factor analysis was performed using the log-rank test and Cox proportional hazards regression. Predictive factors for pathologic CRT response were determined using multivariate logistic regression. Results: Elevated CEA levels (> 5 ng/mL) were observed in 201 (33.0%) patients at diagnosis. Following preoperative CRT, a downstaging (ypStage 0–I) occurred in 255 (41.9%) patients, of whom 88 had pathologic complete tumor regression. The median follow-up period was 60 months, and the 5-year disease-free and overall survival rates