Mar 7, 2014 - PG 6.2. SPEAKER ABSTRACT. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs.
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European Journal of Cancer 50, suppl. 1 (2014) S1–S8
operated on immediately after post-treatment assessment. LR after the first 12 months was almost always amenable to salvage surgery of the time. There were no oncologic differences between patients undergoing immediate radical resection compared to those who sustained a cCR for 12 months or longer. Conflict of interests: No conflict of interests PG 6.2 SPEAKER ABSTRACT Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin vs. capecitabine alone in locally advanced rectal cancer: disease free survival results at interim analysis H-J. Schmoll, K. Haustermans, T. Price, B. Nordlinger, R.D. Hofheinz, J-F. Daisne, J. Janssens, B. Brenner, P. Schmidt, H. Reinel, S. Hollerbach, K. Caca, F. Fauth, C.V. Hannig, J. Zalcberg, N. Tebbutt, M.E. Mauer, C. Messina, M. Lutz, E. Van Cutsem, for the EORTC GITCG, AIO, AGITG, EORTC ROG, BGDO, FFCD Background: The PETACC-6 trial investigates whether the addition of oxaliplatin to preoperative oral fluoropyrimidine-based chemoradiation (CRT) followed by postoperative adjuvant fluoropyrimidine-based chemotherapy (CT) improves disease-free survival (DFS) in locally advanced rectal cancer. Methods: Between 11/2008 and 09/2011, patients with rectal cancer within 12 cm from the anal verge, T3/4 and/or node-positive, with no evidence of metastatic disease and considered either resectable at the time of entry or expected to become resectable, were randomly assigned to receive 5 weeks of preoperative CRT with capecitabine, followed by 6 cycles of adjuvant CT with capecitabine (arm 1) with or without the addition of oxaliplatin before and after surgery (arm 2). 440 DFS events were required to have 80% power to detect an improvement in 3-year DFS from 65% with capecitabine alone to 72% with capecitabine and oxaliplatin (HR = 0.763) using a two-sided alpha of 5% and owing for an interim analysis for early efficacy at 200 events. The primary analysis was intent-to-treat and adjusted for stratification factors (clinical T category, nodal status, distance from the tumor to the anal verge and method of locoregional staging) but the center. Results: 1094 patients were randomized (547 in each arm). 98% and 92% of patients respectively, received at least 45 Gy of preoperative RT in arm 1 and arm 2. More than 90% of full dose concurrent CT was delivered in 91% and 63% of patients in arm 1 and 2 respectively; 68% and 53% of patients completed 6 cycles of postoperative CT. At median follow-up of 23 months, there is no difference in locoregional control. Conclusions: Interim results did not show early efficacy but support that the addition of oxaliplatin does not improve locoregional control in this setting. This is in accordance with three of the four previous trials comparing 5FU with 5FU/Oxaliplatin in the preoperative chemoradiaton indicating that the standard remains 5FU, preferably oral capecitabine. Conflict of interests: No conflict of interests PG 6.3 SPEAKER ABSTRACT Is there a need for adjuvant chemotherapy after combined modality treatment? E. Van Cutsem. Leuven Cancer Institute, Leuven, Belgium
Invited Publications
treatment. On the other hand, there is evidence and consensus that only the resection of all tumour cells can lead to long-term survival. For both reasons, new strategies for advanced synchronous liver metastases should include a very effective neoadjuvant chemotherapy followed by R0 surgery. Neoadjuvant chemotherapy allows to resect patients who were unresectable and to select patients who respond or stabilize for surgery, as opposed to patients in whom the disease progresses despite chemotherapy [1]. Furthermore, in a majority of cases, the neoadjuvant chemotherapy has also an impact on the primary tumour of the colon or rectum. Despite the high response rate to chemotherapy in advanced colorectal liver metastases (about 80% with new agents), however, a sustained response is limited in time allowing only a window of some months to eradicate surgically viable cancer cells that persist after chemotherapy. Several arguments support a strategy that considers the liver metastases as the primary target of both chemotherapy and surgery and that operates on the liver first: (a) The use of powerful systemic chemotherapy as the initial step allows immediate treatment of the liver disease, which constitutes the most imminent threat to the patient’s life. (b) By applying chemotherapy first it is possible to select patients in whom a curative treatment can still be attempted. (c) Among responders, removing all known liver metastases first protects from re-growth of the liver lesions while optimal treatment is given to the primary tumour (e.g. preoperative radiotherapy for rectal cancer can be given without the fear that liver metastases will meanwhile progress beyond the possibility of cure, or that complications of colorectal surgery would further delay the start of chemotherapy). (d) In many cases, the decreased size of the liver metastases allows more conservative − yet radical − resections that spare liver parenchyma. Concerning the liver-first approach, however, some caveats should be remembered: although this new strategy may be ideally suited to patients whose liver metastases represent the main threat, it cannot be recommended yet for patients with obstructive symptoms or advanced rectal tumours in whom treatment of the colorectal primary must come first. Another concern is that the optimal timing for resection is limited and requires careful multidisciplinary surveillance [1]. In conclusion, high-impact neoadjuvant chemotherapy first, followed by resection of liver metastases as a second step, and removal of the primary tumour last appears as a promising approach in patients with advanced synchronous liver metastases from colorectal cancer. The liver first approach was associated with a high rate of curative resections and with improved long-term survival for patients with advanced disease (median number of metastases 6, median size of the largest 6 cm) in our experience (60% at 3 years and 31% at 5 years) [3]. Reference(s) [1] Adam R, et al. Tumor progression while on chemotherapy. A contraindication to liver resection for multiple colorectal metastases? Ann Surg 2004; 240: 1052–1064. [2] Mentha G., et al. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg 2006; 93: 872–878. [3] Mentha G., et al. Liver first approach in the treatment of colorectal cancer with synchronous liver metastases. Dig Surg 2008; 25: 430−35. Conflict of interests: No conflict of interests
Abstract not available. PG 7.2 SPEAKER ABSTRACT Limits of resectability and how to overcome them
Friday, 7 March 2014, 14:00−15.30
Session 7: Rectal cancer with synchronous liver metastases I Chairs: Gunnar Folprecht (Germany), Robert Glynne-Jones (UK) PG 7.1 SPEAKER ABSTRACT Liver First Approach in synchronous liver metastases from colorectal cancer G. Mentha1 . 1 Department of Surgery and HPB Centre, University Hospitals of Geneva, Switzerland Synchronous liver metastases are associated to a particular poor outcome. For synchronous liver metastases, the standard treatment is either resection of the primary tumour at the same time as the liver metastases, followed by chemotherapy, or resection of the primary tumour followed by chemotherapy for 3−6 months, with the aim of removing the liver metastases if they stabilize or respond. Unfortunately, most hepatic metastases are inoperable because of tumour number, size and location. Patients with multiple or large synchronous liver metastases or with locally advanced rectal tumours are at particular risk of a poor outcome as the liver disease may progress beyond the possibility of cure during treatment of the primary, especially if complications of colorectal surgery are encountered. When synchronous liver metastases of a colorectal cancer are present, the disease can be considered as systemic and it is logical to use a systemic
´ Universite´ de Bordeaux, France S. Evrard1 . 1 Institut Bergonie, Introduction: Despite survival rates of 40 months achieved by chemotherapy in patients with liver only colorectal metastases, surgical curability still remains the real cut-off point, offering 5-year survivals between 33 and 56%. Deciding on resectability however is a challenge for the surgeon, who has to deal subjectively with multiple objective parameters. Where are the limits? Anatomical limitations include an unfavorable right/left repartition and previous hepatectomies. De facto, liver homeostasis is affected after each line of surgery. One portal pedicule, two segments and one hepatic vein are the minimum anatomical structures to spare. Technical limitations are mainly vascular. Juxta-portal LM are mostly resected R1 and not R0 as hyperthermic ablation is contra-indicated due to biliary duct sensitivity. Ablation with vascular exclusion is a good approach to treat LM close to a hepatic vein. Lastly, a scared Glisson capsulae is an obstacle to the ultrasounds guidance. Oncologic limitations are no longer based on a maximal metastases number even if, it keeps some prognostic evidence. Extra-hepatic disease is no longer a contra-indication providing it is limited. Nevertheless, it remains a poor prognostic factor. Conversion chemotherapy can limit the technical possibilities due to induced toxicities. How to overcome them? MDT meetings every four cures of chemotherapy are key for an optimal management pathway: preoperative treatment toxicity must be kept to a minimum and the patient should be resected as soon as possible. Portal vein obliteration can be used to cause atrophy of the invaded segments and hypertrophy of the healthy ones. Surgery can be planned as
