- Email: [email protected]
53. Optimal timing of surgery after neoadjuvant chemo-radiation therapy in locally advanced rectal cancer
ABSTRACTS Background: The indication for resection of the primary tumour in patients with asymptomatic metastatic colorectal cancer is under debate. So far, there are no results from RCTs; the CAIRO4 study is still enrolling patients and these results should be awaited. Several retrospective studies suggested a survival benefit in patients who underwent resection of the primary tumour, but bias due to confounding by indication is highly likely. Comparative Effectiveness Research, by using country as instrumental variable, could provide clues to the best treatment strategy for asymptomatic incurable metastatic colorectal cancer. Material and methods: Population-based cohorts (2007e2013) from the Netherlands and Norway including all patients with synchronous metastatic colorectal cancer (who had no surgery of metastatic disease) were compared on treatment strategy and overall survival. Using country as an instrumental variable (pseudo-randomisation), we assessed the effect of different treatment strategies on mortality within the first year. Analyses were adjusted for age, gender, localisation, year of diagnosis, and localisation of metastases. Results: Overall, 21,196 patients were included; 16,144 Dutch patients and 5,052 Norwegian patients. The proportion of patients who had surgery of the primary tumour was 38.6% in the Netherlands compared with 51.5% in Norway (p < 0.001). Of all Dutch patients, 58.4% received chemotherapy compared with 21.4% of Norwegian patients. Radiotherapy was given in 10.2% of Dutch patients compared with 11.2% of Norwegian patients. With the Netherlands as a reference category, the adjusted HR for overall survival was 0.98 (95% CI 0.93e1.03; p ¼ 0.36). Instrumental variable analysis showed an adjusted OR of 1.00 (95% CI 0.98e1.03; p ¼ 0.72). Conclusions: The present international comparison shows variations in treatment strategy between the Netherlands and Norway. However, we did not observe a difference in overall survival between these countries. Instrumental variable analysis showed no benefit of a treatment strategy with more surgery of the primary tumour on mortality within the first year. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2016.06.058
53. Optimal timing of surgery after neoadjuvant chemo-radiation therapy in locally advanced rectal cancer Z. Gad1, W. Gareer1, H. El Hossieny2, A. Naguib3, S. Abo Amer1 1 NCI e Cairo University, Surgical Oncology, Cairo, Egypt 2 NCI e Cairo University, Radiotherapy, Cairo, Egypt 3 NCI e Cairo University, Medical Oncology, Cairo, Egypt Background: Surgery is the corner stone for the management of rectal cancer. An unsolved aspect of neoadjuvant chemo-radiation is the appropriate timing of surgery after completion of neoadjuvant chemo-radiation. The purpose of this study was to demonstrate the optimal time of surgical resection after the completion of neoadjuvant chemo-radiotherapy in treatment of locally advanced rectal cancer. Material and methods: This study compared 2 groups of patients with locally advanced rectal cancer, treated with neoadjuvant chemo-radiotherapy followed by surgical resection either 6e8 weeks (group 1) or 9e14 (group 2) weeks after the completion of chemo-radiotherapy. The impact of delaying surgery was tested in comparison to early surgical resection after completion of chemo-radiotherapy. Results: There was no statistically significant difference between the 2 groups regarding treatment toxicity. The difference between the two groups regarding the type of surgery was statistically not significant (P ¼ 0.382). The total significant response rate that could result in functional preservation was estimated to be 3.85% in group I and 15.38% in group II. 9.62% of our patients had residual malignant cells at one cm surgical margin. All those patients with positive margins at one cm were in group I (19.23%). No patients in group II had positive margins at 1 cm (0%). There was less operative time in group II, but the difference between both groups was statistically insignificant (P ¼ 0.845). The difference between both groups regarding operative blood loss and intra operative blood transfusion was significantly less in group II (P ¼ 0.044). There was no
S87 statistically significant difference between both groups regarding the intra operative complications (P ¼ 0.609). The current study showed significantly less post-operative hospital stay period, and less post-operative wound infection in group II (P ¼ 0.012 and 0.017). The current study showed more tumor regression and necrosis in group II with a highly significant main effect of time F ¼ 61.7 (P < 0.001). Pathological TN stage indicated better pathological tumor response in group II (P ¼ 0.04). Pathological complete response rate was reported in only one patient in group I (3.85%), and in 7/26 patients (26.92%) in group II. The current study showed recurrence free survival for all cases at 18 months of 84.2%. In group I, survival rate at the same duration was 73.8%, however none of group II cases had local recurrence (censored). The difference was of statistical significance (P ¼ 0.031). Disease free survival (DFS) during the same duration (18 months) was 69.4% for patients in group I and 82.3% for group II. The difference was of no statistical significance (P ¼ 0.429). Conclusion: Surgical resection delay up to 9e14 weeks after chemoradiation was associated with better outcome and better recurrence free survival. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2016.06.059
54. Proactive treatment of pelvic T4 locally advanced and recurrent colorectal cancer C. Sassaroli1, A. Cassata2, O. Catalano3, E. Cardone1, F. Ruffolo1, P. Delrio1 1 National Cancer Institute of Naples, Colorectal Surgery, Naples, Italy 2 National Cancer Institute of Naples, Abdominal Oncology, Naples, Italy 3 National Cancer Institute of Naples, Radiology, Naples, Italy Introduction: Colorectal cancer with localized pelvic disease is amenable to a curative approach. Even more advanced cases, including T4 tumours and recurrent pelvic cancer can be managed with extensive surgery to achieve local control. Peritoneal involvement can also be dealed with and early referral or simultaneous HIPEC (Hyperthermic Perioperative Chemotherapy), together with appropriate surgery; it may be able to provide a complete clearance of the primary cancer and prevent intraabdominal diffusion of the disease. Patients and methods: From 2010 to 2015, among 50 consecutive pelvectomies performed both for pelvic recurrence or locally advanced rectosigmoid tumors, we performed simultaneous HIPEC (proactive treatment) in 13 patients. Total pelvectomy was performed in 3 patients: 2 for T4 tumors (1 mucinous) and one for pelvic recurrence (mucinous); posterior pelvectomy was performed in 10 patients: 3 for T4 tumors (all mucinous) and 7 for pelvic recurrence (4 mucinous). All patients received extended pelvic peritonectomy, intraperitoneal oxaliplatin with systemic 5 e Fluorouracil for a 30 min HIPEC treatment. Peritoneal dissection was started at the transverse umbilical line. Results: Among patients treated with HIPEC there were 4 Clavien Dindo grade IIIeIV complications. No postoperative death occurred. The median postoperative hospital stay was 17 days. Up to date 11 patients are disease free: respectively after 64, 52, 47, 40, 38, 26, 25, 17, 4 and 3 months. Of these, 1 patient developed liver disease and is now disease free after chemotherapy; 1 patient, pre-treated with chemotherapy for a lung metastasis before proactive HIPEC, underwent lung resection after abdominal surgery; 2 patients underwent an APR for recurrent cancer on rectal stump and colorectal anastomosis respectively. None of these patients developed a peritoneal recurrence. One patient died after 20 months with a huge pelvic recurrence of a G3 mucinous tumour and 1 patient is alive at 30 months with metastatic disease (liver and lung). Conclusions: In high risk patients (peritoneal involvement, ovarian metastases, perforated tumours, previous R1-2 resections or intraoperative tumour disruption, positive cytology, adjacent organs involvement, T3 mucinous tumor, T4 cancers) “proactive” HIPEC is a very promising treatment option to prevent intra-abdominal diffusion of pelvic disease. Our
53. Optimal timing of surgery after neoadjuvant chemo-radiation therapy in locally advanced rectal cancer Z. Gad1, W. Gareer1, H. El Hossieny2, A. Naguib3, S. Abo Amer1 1 NCI e Cairo University, Surgical Oncology, Cairo, Egypt 2 NCI e Cairo University, Radiotherapy, Cairo, Egypt 3 NCI e Cairo University, Medical Oncology, Cairo, Egypt Background: Surgery is the corner stone for the management of rectal cancer. An unsolved aspect of neoadjuvant chemo-radiation is the appropriate timing of surgery after completion of neoadjuvant chemo-radiation. The purpose of this study was to demonstrate the optimal time of surgical resection after the completion of neoadjuvant chemo-radiotherapy in treatment of locally advanced rectal cancer. Material and methods: This study compared 2 groups of patients with locally advanced rectal cancer, treated with neoadjuvant chemo-radiotherapy followed by surgical resection either 6e8 weeks (group 1) or 9e14 (group 2) weeks after the completion of chemo-radiotherapy. The impact of delaying surgery was tested in comparison to early surgical resection after completion of chemo-radiotherapy. Results: There was no statistically significant difference between the 2 groups regarding treatment toxicity. The difference between the two groups regarding the type of surgery was statistically not significant (P ¼ 0.382). The total significant response rate that could result in functional preservation was estimated to be 3.85% in group I and 15.38% in group II. 9.62% of our patients had residual malignant cells at one cm surgical margin. All those patients with positive margins at one cm were in group I (19.23%). No patients in group II had positive margins at 1 cm (0%). There was less operative time in group II, but the difference between both groups was statistically insignificant (P ¼ 0.845). The difference between both groups regarding operative blood loss and intra operative blood transfusion was significantly less in group II (P ¼ 0.044). There was no
S87 statistically significant difference between both groups regarding the intra operative complications (P ¼ 0.609). The current study showed significantly less post-operative hospital stay period, and less post-operative wound infection in group II (P ¼ 0.012 and 0.017). The current study showed more tumor regression and necrosis in group II with a highly significant main effect of time F ¼ 61.7 (P < 0.001). Pathological TN stage indicated better pathological tumor response in group II (P ¼ 0.04). Pathological complete response rate was reported in only one patient in group I (3.85%), and in 7/26 patients (26.92%) in group II. The current study showed recurrence free survival for all cases at 18 months of 84.2%. In group I, survival rate at the same duration was 73.8%, however none of group II cases had local recurrence (censored). The difference was of statistical significance (P ¼ 0.031). Disease free survival (DFS) during the same duration (18 months) was 69.4% for patients in group I and 82.3% for group II. The difference was of no statistical significance (P ¼ 0.429). Conclusion: Surgical resection delay up to 9e14 weeks after chemoradiation was associated with better outcome and better recurrence free survival. Conflict of interest: No conflict of interest. http://dx.doi.org/10.1016/j.ejso.2016.06.059
54. Proactive treatment of pelvic T4 locally advanced and recurrent colorectal cancer C. Sassaroli1, A. Cassata2, O. Catalano3, E. Cardone1, F. Ruffolo1, P. Delrio1 1 National Cancer Institute of Naples, Colorectal Surgery, Naples, Italy 2 National Cancer Institute of Naples, Abdominal Oncology, Naples, Italy 3 National Cancer Institute of Naples, Radiology, Naples, Italy Introduction: Colorectal cancer with localized pelvic disease is amenable to a curative approach. Even more advanced cases, including T4 tumours and recurrent pelvic cancer can be managed with extensive surgery to achieve local control. Peritoneal involvement can also be dealed with and early referral or simultaneous HIPEC (Hyperthermic Perioperative Chemotherapy), together with appropriate surgery; it may be able to provide a complete clearance of the primary cancer and prevent intraabdominal diffusion of the disease. Patients and methods: From 2010 to 2015, among 50 consecutive pelvectomies performed both for pelvic recurrence or locally advanced rectosigmoid tumors, we performed simultaneous HIPEC (proactive treatment) in 13 patients. Total pelvectomy was performed in 3 patients: 2 for T4 tumors (1 mucinous) and one for pelvic recurrence (mucinous); posterior pelvectomy was performed in 10 patients: 3 for T4 tumors (all mucinous) and 7 for pelvic recurrence (4 mucinous). All patients received extended pelvic peritonectomy, intraperitoneal oxaliplatin with systemic 5 e Fluorouracil for a 30 min HIPEC treatment. Peritoneal dissection was started at the transverse umbilical line. Results: Among patients treated with HIPEC there were 4 Clavien Dindo grade IIIeIV complications. No postoperative death occurred. The median postoperative hospital stay was 17 days. Up to date 11 patients are disease free: respectively after 64, 52, 47, 40, 38, 26, 25, 17, 4 and 3 months. Of these, 1 patient developed liver disease and is now disease free after chemotherapy; 1 patient, pre-treated with chemotherapy for a lung metastasis before proactive HIPEC, underwent lung resection after abdominal surgery; 2 patients underwent an APR for recurrent cancer on rectal stump and colorectal anastomosis respectively. None of these patients developed a peritoneal recurrence. One patient died after 20 months with a huge pelvic recurrence of a G3 mucinous tumour and 1 patient is alive at 30 months with metastatic disease (liver and lung). Conclusions: In high risk patients (peritoneal involvement, ovarian metastases, perforated tumours, previous R1-2 resections or intraoperative tumour disruption, positive cytology, adjacent organs involvement, T3 mucinous tumor, T4 cancers) “proactive” HIPEC is a very promising treatment option to prevent intra-abdominal diffusion of pelvic disease. Our