Advances in Radiotherapy in Operable Rectal Cancer (original) (raw)
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Outcomes following a limited approach to radiotherapy in rectal cancer
British Journal of Surgery, 2011
Background: Variation in the use of neoadjuvant and adjuvant radiotherapy for rectal cancer suggests an opportunity to avoid it in all but patients at highest risk of local recurrence. Methods: Between 1 July 1999 and 1 February 2006, patients with primary rectal cancer were treated by a single surgeon operating at McMaster University, Hamilton, Ontario, Canada. Digital rectal examination and pelvic computed tomography were used to determine whether the mesorectal margin was threatened by tumour and thus whether preoperative radiotherapy would be needed. The study outcome was local tumour recurrence.
Current evidence does not support routine adjuvant radiotherapy for rectal cancer
ANZ Journal of Surgery, 2002
Background : There is widespread support in the published literature for routine adjuvant radiotherapy for rectal cancer. Methods : In the present paper, the current evidence regarding adjuvant radiotherapy is reviewed, particularly the most recent studies of preoperative radiotherapy (usually including patients with Stage I, II and III disease) and postoperative radiotherapy (usually for Stage II and III disease), and meta-analyses. Two questions in particular are addressed: Does radiotherapy improve survival when surgeons are able to achieve low local recurrence rates with surgery alone? Does radiotherapy improve patients' quality of life? Results : Radiotherapy has only been demonstrated to significantly improve survival in one individual study and one recent metaanalysis. The local recurrence rates in the no-radiotherapy arm of these studies were 27% and 21-36.5%, respectively. In more recent studies, with lower local recurrence rates reflecting modern surgical standards, no survival advantage has been found. It is currently unknown whether radiotherapy improves patients' quality of life. Studies have demonstrated that radiotherapy has acute and long-term detrimental effects on quality of life. While local recurrence can be very debilitating, it can also be asymptomatic, and the overall effect of the local recurrence statistics found in adjuvant therapy studies on quality of life has not been systematically investigated. The most recent studies demonstrate that 17-20 patients need to undergo adjuvant radiotherapy to prevent one local recurrence. Conclusion : Current evidence does not support the widespread advocacy for routine adjuvant radiotherapy as used in the treatment arms of recent trials.
Current treatment of rectal cancer adapted to the individual patient
Reports of Practical Oncology & Radiotherapy, 2013
Preoperative radiochemotherapy and total mesorectal excision surgery is a recommended standard therapy for patients with locally advanced rectal cancer. However, some subgroups of patients benefit more than others from this approach. In order to avoid long-term complications of radiation and chemotherapy, efforts are being made to subdivide T3N0 stage using advanced imaging techniques, and to analyze prognostic factors that help to define subgroup risk patients. Long-course radiochemotherapy has the potential of downsizing the tumor before surgery and may increase the chance of sphincter preservation in some patients. Short-course radiotherapy (SCRT), on the other hand, is a practical schedule that better suits patients with intermediated risk tumors, located far from the anal margin. SCRT is also increasingly being used among patients with disseminated disease, before resection of the rectal tumor. Improvements in radiation technique, such as keeping the irradiation target below S2/S3 junction, and the use of IMRT, can reduce the toxicity associated with radiation, specially long-term small bowel toxicity.
BMC Cancer, 2009
The additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control.
Radiotherapy and Oncology, 2011
Purpose: To assess efficacy and tolerance of intra-operative radiation therapy (IORT) in patients suffering from locally advanced rectal cancer, treated with preoperative radiotherapy followed by surgical resection. Methods and materials: In this French, multicenter, comparative, phase III study, 142 patients with locally advanced rectal cancer (T3 or T4 or N+, and M0), treated with a 4-week preoperative radiotherapy (40 grays) were randomly assigned to either surgical resection alone (Control group: n = 69) or combined to 18-gray intra-operative radiation therapy (IORT group: n = 73) between 1993 and 2001. Results: The 5-year cumulative incidence of local control was 91.8% with IORT and 92.8% with surgery alone (p = 0.6018); the mean duration without local relapse (Kaplan-Meier method) was 107 versus 126 months, respectively. No statistically significant difference was demonstrated for overall survival (p = 0.2578) disease-free survival (p = 0.7808) and probability of metastatic relapse (p = 0.6037) with 5-year cumulative incidences of 69.8% versus 74.8%, 63.7% versus 63.1%, and 26.1% versus 30.2%, respectively. 48 patients of the IORT group and 53 patients of the control group were alive with a median follow-up of 60.1 and 61.2 months, respectively. Post-operative complications were observed in the IORT group in 21 patients (29.6%) and in the control group in 13 patients (19.1%) (p = 0.15), with an acceptable tolerance profile. Conclusions: Although this randomized study did not demonstrate any significant improvement in local control and disease-free survival in rectal cancer patients treated with preoperative radiation therapy receiving IORT or not, it confirmed the technical feasibility and the necessity for evaluating IORT for rectal carcinoma in further clinical studies.
Rectal cancer treatment: Improving the picture
World Journal of Gastroenterology, 2007
therapy with radiotherapy improved local tumor control and survival in stage Ⅱ and Ⅲ rectal cancer relative to surgery alone. Although currently the big picture mostly remains, some of the characters of the puzzle have changed. The main milestones in this development began with the improvement of the surgical technique, total mesorectal excision (TME). TME became the choice surgical procedure, with a relevant increase in local control. Actually, at some point it was thought that TME could make radiotherapy (RT) unnecessary. Nevertheless, a randomized study soon followed showing the maintained benefit of RT despite an excellent surgery, at least in terms of local control [4] , outcomes that even are improving with longer follow-up. The second landmark was to move the CHRT segment before the surgery. Initially, preoperative radiotherapy was found to improve overall survival as compared with surgery alone [5,6]. In the last decade, the dominant tendency in the therapeutic development of rectal cancer, both in Europe and North America, has been the use of preoperative radiotherapy with conventional protracted fractionation (45-50 Gy in daily fractions of 1.8-2 Gy during 5-6 wk) with concurrent chemotherapy followed by surgery at 4-8 wk. Extensive experience with preoperative CHRT showed feasibility and promising results in terms of down staging, sphincter preservation and disease control and survival parameters as interesting elements of analysis, with an acceptable toxicity profile. The most frequently used chemotherapy agent in this clinical context is 5-fluorouracil (5-FU, i.v.) [7-13]. More recently, the only phase Ⅲ trial concluded comparing pre-vs post-operative CHRT, demonstrated better tolerance, sphincter-saving surgical procedures and local control with preoperative CHRT [14]. Preoperative radiotherapy alone (no chemotherapy) and delayed surgery reported down staging rates of 18% [15,16]. However, the prolonged administration of CH-RT achieves down staging figures of around 65% [7-11,17]. Additionally, induction of tumor down staging improves the probability of a complete resection and sphincterpreserving surgery [11,13,18-20]. Complete pathologic response (pCR) rates range from 8% to 27% using i.v. 5-FU with preoperative irradiation [7,10,11,14,21]. In studies of postoperative 5-FU-based CHRT, severe acute toxicity ranges from 24%-40% [1,14,22,23]. However, in Phase Ⅱ studies of preoperative CH-RT, Grade 3-4 acute toxicity occurs in 15%-28% of patients [7,11,13,14,20]. Regarding tumor control and survival, published series
A trial of preoperative radiotherapy in the management of operable rectal cancer
British Journal of Surgery, 1982
In a multicentre study, 824 patients with operable rectal cancer were randomized to receive surgery alone, surgery plus a single fraction of 500 rad (5 Gy) and surgery plus 2000 rad (20 Gy) in 10 equal daily, i.e. multiple, fractions. The ratio of abdominoperineal excision to anterior restorative operations was 3:1. There was no evidence of an increased morbidity or mortality following irradiation. The multiple fraction 2000 rad group had tumours which were significantly smaller than those of the other groups. There was also a reduction in the Dukes' C cases in the multiple fraction group. Neither the tumour size nor the lymph node status was altered in the single fraction group.