Preoperative Radiotherapy For Rectal Cancer Research Articles

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Quality of life, anorectal and sexual functions after preoperative radiotherapy for rectal cancer: Report of a randomised trial

Background and purpose Patients ( N = 316) with resectable cT3-4 low-lying and mid-rectal cancer were randomised to receive either preoperative 5 × 5 Gy irradiation with subsequent surgery performed within 7 days or chemoradiation (50.4, 1.8 Gy per fraction plus boluses of 5-fluorouracil and leucovorin) followed by surgery after 4–6 weeks. No differences were found in sphincter preservation, survival, local control and late complications. Early complications were less frequent in the short-course group. The aim of this report is to find out whether large doses per fraction of short-course schedule result in more severe anorectal and sexual dysfunction and quality of life (QoL) impairment. Materials and method Patients who were free of disease were asked to answer the QLQ-C30 and those without stoma were, additionally, asked to fill in a questionnaire of anorectal (19 items) and sexual function (1 item). Results Two hundred and twenty-two patients (86% response rate) completed the QLQ-C30 and 118 (86% response rate) the anorectal–sexual function questionnaire. The median time from surgery to filling in the QLQ-C30 questionnaire was 12 months, and to filling in the anorectal–sexual function questionnaire – 13 months. We did not find significant differences between the randomised groups regarding QoL and the anorectal and sexual functions. Approximately two-thirds of patients had anorectal function impairment. Approximately 20% of patients stated that this considerably influenced their QoL. Conclusions QoL and the anorectal and sexual functioning did not differ in patients receiving short-course radiotherapy, as compared to those receiving chemoradiation.

MRI after preoperative radiotherapy for rectal cancer; correlation with histopathology and the role of volumetry

The objective is to assess if tumor size after radiotherapy in patients with rectal cancer can be assessed by a second magnetic resonance imaging (MRI), after radiotherapy prior to surgery and to correlate changes observed on MRI with findings at histopathology at surgery. Twenty-five patients with MRI before and after radiotherapy were included. Variables studied were changes in tumor size, T-staging and distance to the circumferential resection margin (CRM). RVs was measured as tumor volume at surgery (Vs) divided by tumor volume at the initial MRI (Vi) in percent. RVm was defined as the tumor volume at the second MRI (Vm) divided by Vi in percent. The ypT-stage was the same or more favorable than the initial MRI T-stage in 24 of 25 patients. The second MRI was not more accurately predictive than the initial MRI for ypT-staging or distance to CRM (p > 0.05). Vm correlated significantly to Vs, as did RVs to RVm, although the former was always smaller than the latter. Vm and RVm correlated well with ypT-stage (p < 0.001). Volumetry seems to correlate with ypT-stage after preoperative radiotherapy for resectable rectal cancer. The value of a second MRI after radiotherapy for assessment of distance to CRM and ypT-staging is, however, not apparent.

Is the timing of chemotherapy important in patients undergoing preoperative radiotherapy for rectal cancer?

Is the timing of chemotherapy important in patients undergoing preoperative radiotherapy for rectal cancer?

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Late adverse effects of short-course preoperative radiotherapy in rectal cancer

Preoperative radiotherapy improves local control and survival in rectal cancer, but there are few reports on long-term morbidity. The aims of this study were to compare long-term morbidity and quality of life in patients undergoing rectal cancer surgery with or without preoperative radiotherapy. A total of 252 patients, randomized within the two Stockholm trials on preoperative radiotherapy in rectal cancer, were alive at a mean of 15 years after surgery. Some 139 of these patients were available for follow-up by questionnaires and clinical examination. Questionnaires regarding medical history and quality of life were completed by all patients. All patients had a clinical examination, and those without a stoma underwent rigid sigmoidoscopy. Overall, patients who had preoperative radiotherapy experienced significantly more late complications than those who did not (69 versus 43 per cent; P = 0.002). This morbidity consisted mainly of cardiovascular disease (35 versus 19 per cent; P = 0.032), faecal incontinence (12 of 21 versus 11 of 42 patients having anterior resection; P = 0.013) and urinary incontinence (45 versus 27 per cent; P = 0.023). No significant differences between groups were found for hip or pelvic fractures, small bowel obstruction or global quality of life. Preoperative short-course, high-dose radiotherapy in patients with rectal cancer increases the risk of anal and urinary dysfunction, and may lead to increased cardiovascular morbidity, at long-term follow-up.

The impact of the Calman–Hine report on the processes and outcomes of care for Yorkshire's colorectal cancer patients

The 1995 Calman–Hine plan outlined radical reform of the UK's cancer services with the aim of improving outcomes and reducing inequalities in NHS cancer care. Its main recommendation was to concentrate care into the hands of site-specialist, multi-disciplinary teams. This study aimed to determine if the implementation of Calman–Hine cancer teams was associated with improved processes and outcomes of care for colorectal cancer patients. The design included longitudinal survey of 13 colorectal cancer teams in Yorkshire and retrospective study of population-based data collected by the Northern and Yorkshire Cancer Registry and Information Service. The population was all colorectal cancer patients diagnosed and treated in Yorkshire between 1995 and 2000. The main outcome measures were: variations in the use of anterior resection and preoperative radiotherapy in rectal cancer, chemotherapy in Dukes stage C and D patients, and five-year survival. Using multilevel models, these outcomes were assessed in relation to measures of the extent of Calman–Hine implementation throughout the study period, namely: (i) each team's degree of adherence to the Manual of Cancer Service Standards (which outlines the specification of the ‘ideal’ colorectal cancer team) and (ii) the extent of site specialisation of each team's surgeons. Variation was observed in the extent to which the colorectal cancer teams in Yorkshire had conformed to the Calman–Hine recommendations. An increase in surgical site specialisation was associated with increased use of preoperative radiotherapy (OR=1.43, 95% CI=1.04–1.98, P<0.04) and anterior resection (OR=1.43, 95% CI=1.16–1.76, P<0.01) in rectal cancer patients. Increases in adherence to the Manual of Cancer Service Standards was associated with improved five-year survival after adjustment for the casemix factors of age, stage of disease, socioeconomic status and year of diagnosis, especially for colon cancer (HR=0.97, 95% CI=0.94–0.99 P<0.01). There was a similar trend of improved survival in relation to increased surgical site specialisation for rectal cancer, although the effect was not statistically significant (HR=0.93, 95% CI=0.84–1.03, P=0.15). In conclusion, the extent of implementation of the Calman–Hine report has been variable and its recommendations are associated with improvements in processes and outcomes of care for colorectal cancer patients.

Chemotherapy with Preoperative Radiotherapy in Rectal Cancer

Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer. We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival. We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%. In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].).

Intensity-modulated radiotherapy with a belly board for rectal cancer

Intensity-modulated radiotherapy (IMRT) techniques can reduce the irradiated small bowel volume in rectal cancer patients, but combined use of IMRT and a belly board is yet to be reported on for rectal cancer patients. The aim of this study was to determine whether additional use of a belly board reduced the irradiated small bowel volume observed using IMRT alone in rectal cancer patients. Twenty patients scheduled to receive preoperative radiotherapy for rectal cancer underwent two series of CT scans, with and without a belly board. IMRT planning was performed using 6-MV photon beams and seven equispaced fields. The bladder, small bowel, and planning target volume (PTV) were analyzed for doses between 10% and 100% of the prescribed dose at 10% intervals. Data were analyzed using Wilcoxon signed rank tests. There were no significant differences between patients undergoing IMRT with a belly board and those without a belly board in terms of total small bowel volumes, bladder, and PTV (p=0.571, p=0.841, and p=0.870, respectively). Statistical analysis showed that the irradiated small bowel volume with a belly board was smaller than that without a belly board (p<0.05 at 20-100% dose levels), with the mean relative reduction in the irradiated small bowel volume being 37.8+/-32.8%. IMRT with a belly board is more effective than IMRT alone in reducing the irradiated small bowel volume. These findings suggest that the use of a belly board with IMRT may reduce small bowel complications in preoperative radiotherapy.

Mortality trends in colorectal cancer (CRC) and influencing factors

13527 Background: A decline in overall cancer death rate was observed in the early 1990s after more than six decades of increase in cancer mortality. Effective prevention, screening and early detection as well as improved treatment strategies may be influencing factors. The aim of this study is to compare the overall survival of patients (pts) with CRC in two different years using our prospective regularly updated register database. Methods: Patients diagnosed of CRC during 1996 and 2000 were included in the study. To analyse the relation between variables the exact Fisher test was used. Survival curves were constructed according to the Kaplan-Meier method and compared by log rank analysis. Analyses were performed using the SPSS package. Results: 289 pts in 1996 and 380 in 2000 were included. Demographic data and tumour characteristics were similar in both groups. 42% of pts in 1996 and 56% in 2000 had received chemotherapy (ChT) (p&lt;0.05). In adjuvant setting, 41.8% of patients with stage II-III colon cancer received ChT in 1996 and 57.5% in 2000 (p=0.019). ChT schedules for advanced CRC included Oxaliplatin and Irinotecan in 23% of ChT in 1996 and in 68% in 2000 (p&lt;0.005). The number of palliative ChT lines was significantly higher in 2000 (p&lt;0.05). Radiotherapy was administered as part of rectal cancer therapy to 48% of pts 1996 and to 60% in 2000 (p=0.05). From those, preoperative radiotherapy was administered to 21% of pts in 1996 and to 66% in 2000 (p&lt;0.05). 4.1% of all pts were lost of follow up. With a median follow up of 104.5 months (m) for 1996 and 56.3 m for 2000, the 5-year overall survival (OS) was 45% and 61.6% respectively (p&lt;0.001). The 5-year disease free survival (DFS) of pts with radical surgery was 73% and 81% respectively (p=0.09). The median survival of pts with radical surgery that relapse during follow up was 13.4 m in 1996 and 17.6 m in 2000 (p&lt;0.04). There were statistical significant differences in OS between 1996 and 2000 in tumour site, stage II-III cancer and males, not in females. DFS for stages II-III was better in 2000, but no significant differences were observed. Conclusions: A positive CRC mortality trend was observed. The influencing factors were related with the use of ChT as an adjuvant treatment and the addition of new drugs in colon cancer therapies as well as preoperative radiotherapy for rectal cancer. No significant financial relationships to disclose.

Negative influence of delayed surgery on survival after preoperative radiotherapy in rectal cancer

In Europe, until recently the standard treatment for locally advanced rectal cancer was preoperative radiotherapy (RT). The objective of this study was to evaluate the influence on survival of intervals between diagnosis and treatment. The influence on survival of intervals between diagnosis and surgery (Dg-Surg), diagnosis and initiation of RT (Dg-Rad), and completion of RT and surgery (Rad-Surg) was evaluated in a retrospective series of patients treated with preoperative RT. Between 1991 and 1998, 102 patients received treatment with preoperative RT without concomitant chemotherapy at the René Gauducheau Cancer Center. Patients generally received 45 Gy (80%) in 25 fractions over 35 days for T2-T3-T4 N0-N1 M0 rectal adenocarcinoma located mainly (62.7%) in the lower third of the rectum (< or = 5 cm from anal margin). Thirty-five pN1 patients were treated with postoperative chemotherapy. Differences between survival were assessed by the log-rank test, and prognostic factors by the Cox test. Median time was 14.7 weeks for Dg-Surg, 4.6 weeks for Dg-Rad and 5.1 weeks for Rad-Surg. Median follow-up from diagnosis was 57.4 months. Five-year local relapse-free survival was 83.9%, metastasis-free survival 64% and overall survival 60.8%. No factor was predictive of tumour response to RT. Log-rank and multivariate analysis showed that overall survival was significantly influenced by lower-third tumours, pT, pN and Dg-Surg (poorer survival when > or = 16 weeks: OR = 2.59, P = 0.005). Metastasis-free survival correlated significantly with Dg-Surg (> or = 16 weeks: OR = 2.05, P = 0.05). An interval of more than 16 weeks between diagnosis and surgery may reduce overall survival of patients treated with preoperative RT for locally advanced rectal cancer. Surgery should be performed shortly after completion of RT for patients with no possibility of sphincter preservation, or a minimal risk of morbidity from an abdominoperineal excision.

Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary

In many patients with advanced synchronous liver metastases from colorectal tumours, the metastases progress during treatment of the primary, precluding curative treatment. The authors have investigated a management strategy that involves high-impact chemotherapy first, resection of liver metastases second and finally removal of the primary tumour in patients with adverse prognostic factors. Twenty consecutive patients with non-obstructive colonic (nine patients) or rectal (11 patients) cancer and advanced synchronous liver metastases were treated according to this strategy. Median age was 56 years. Patients received between two and six cycles of 5-fluorouracil, oxaliplatin and irinotecan-based chemotherapy. Data were collected prospectively. Overall survival rates at 1, 2, 3 and 4 years after the start of treatment were 85, 79, 71 and 56 per cent respectively, with a median survival of 46 months. Sixteen of the 20 patients had complete removal of liver metastases and colorectal tumours (resectability rate 80 per cent). This new strategy produced resectability and survival rates better than those expected from the published data on patients with disease of similar severity. It allows initial control and downstaging of liver metastases, and delivery of preoperative radiotherapy for rectal cancer without the fear that liver metastases will meanwhile progress beyond the possibility of cure.

Harm and benefits of short-term pre-operative radiotherapy in patients with resectable rectal carcinomas

Aim To weigh the harms and benefits of short-term pre-operative radiotherapy in the treatment of resectable rectal cancer. Methods The benefits (reduction of local recurrence) and harm (increase of short-term complications) of short-term pre-operative radiotherapy are balanced using a model which classifies patients in one of five outcome combinations; 1—benefit without additional harm, 2—benefit with additional harm, 3—no benefit, no additional harm, 4—no benefit but additional harm, 5—mortality due to combined treatment. The results of four randomised clinical trials (RCT) which study the addition of short-term pre-operative radiotherapy in rectal cancer were classified according to this model. Results Five to thirteen percent of the patients have benefit without additional harm of pre-operative radiotherapy, while 0–2% have benefit with additional harm; 74–87% has neither benefit nor additional harm and 6–11% have no benefit but additional harm. A small percentage of patients (1–6%) dies post-operatively as a result of the addition of radiotherapy. Conclusion This model provides a transparent appreciation of the harmful and beneficial effects of any treatment modality investigated by means of a randomised clinical trial. As for short-term pre-operative radiotherapy in resectable rectal cancer is shown, a small percentage of patients benefits from such treatment. Most patients have neither benefit nor additional harm, while a small percentage suffers from additional harm while not receiving any benefit.

Preoperative radiotherapy for rectal cancer: beyond local control

Preoperative radiotherapy for rectal cancer: beyond local control

Is pre‐operative radiotherapy necessary in T1‐T3 rectal cancer with TME?

The indications for pre-operative radiotherapy in rectal cancer are still unclear with the exception of T4 tumours. The aim of this study was to assess local and overall recurrence in patients with T1-T3 rectal cancers undergoing total mesorectal excision (TME). Prospective data was collected from 150 patients with rectal cancer treated in one surgical centre between July 1997 and July 2002. One hundred and twenty-nine primary resections were carried of which 102 were with curative intent. Seventy-nine patients with T1-T3 tumours were included in the analysis. Nine had local resections and 70 underwent TME; 19 of the 70 patients were node positive and 51 were node negative. At a median follow-up of 37 months (range 19-79 months) there were 3 (4.3%) isolated local recurrences. One node positive patient developed isolated local recurrence compared with 2 node negative patients. The node positive patient died from a myocardial infarction while the two node negative patients died as a consequence of local recurrence. Three (4.3%) of 70 patients developed systemic relapse all of whom were node positive. The cancer specific mortality rate over the same follow-up period was 3/19 for node positive patients and 2/51 for node negative patients. Of 9 patients who had local resections, none developed local recurrence or systemic relapse. With TME the rate of local recurrence in T1-T3 tumours is low. Our results do not support the use of pre-operative radiotherapy for these patients.

Clearance technique for the detection of lymph nodes in colorectal cancer.

Lymph node metastases are an important determinant of prognosis following surgery for colorectal cancer. A xylene alcohol clearance technique has been employed in Guildford to facilitate the identification of lymph nodes in the mesorectum of rectal cancer specimens. The numbers of lymph nodes and lymph node metastases were compared with seven other centres and St. Mark's Hospital, where clearance techniques were not employed in patients undergoing a randomized trial of pre-operative radiotherapy for rectal cancer. The total number of lymph nodes identified per patient in the mesorectum of patients at Guildford (mean = 23.1 +/- 1.18) was significantly higher when compared with patients at St. Mark's Hospital alone (mean = 13.1 +/- 0.86) and the seven combined "non-cleared' centres (mean = 10.5 +/- 0.6) (P less than 0.001). The number of lymph node metastases per patient was significantly higher in the Guildford series (mean = 3.21 +/- 0.58) when compared with the seven combined centres (mean = 1.9 +/- 0.3) (P less than 0.05). The numbers of lymph node metastases found in the lowest part of the specimen close to the levator ani were significantly higher in the Guildford patients (mean = 1.2 +/- 0.4) compared with St. Mark's Hospital (mean = 0.13 +/- 0.1) and the seven combined 'non-cleared' centres (mean = 0.56 +/- 0.1). This clearance technique identified not only a greater number of lymph nodes but also more metastases within those nodes, particularly in the supralevator area of the mesorectum.

Enhanced Tumorocidal Effect of Chemotherapy With Preoperative Radiotherapy for Rectal Cancer: Preliminary Results—EORTC 22921

The European Organisation for Research and Treatment of Cancer (EORTC) trial evaluated the addition of chemotherapy (CT) to preoperative radiation (preop RT) and the value of postoperative CT for improving the survival in patients with T3-4 resectable rectal cancer. Patients were allocated to the following four arms: arm 1, preop RT 45 Gy in 5 weeks; arm 2, preop RT plus two 5-day CT courses (fluorouracil 350 mg/m2/d and leucovorin 20 mg/m2/d) in the first and fifth week of RT; arm 3, preop RT plus four postoperative CT courses; and arm 4, preop RT and CT plus postoperative CT. We investigated the effect of adding CT on the pathologic parameters. One thousand eleven patients were entered onto the trial; 505 received preop RT (arms 1 and 3), and 506 received preop RT-CT (arms 2 and 4). We analyzed the differences in tumor size, tumor node stage, number of retrieved nodes, and histologic features such as lymphatic, venous, and perineural invasions, tumor differentiation, and tumor type. After preop RT-CT, tumors were smaller (P < .0001), had less advanced pT (P < .001) and pN stages (P < .001), had small numbers of examined nodes (P = .046), and less frequent LVN invasions (P < or = .008). Mucinous tumors increased after preop RT-CT (P < .001). In patients with rectal cancer, preliminary results of EORTC Trial 22921 indicate that the addition of CT to preop RT induces down-sizing, downstaging, and significant changes in histologic characteristics. Longer follow-up is needed to assess the impact on local control and survival.

Prognostic impact of epidermal growth factor receptor (EGFR) expression on loco-regional recurrence after preoperative radiotherapy in rectal cancer.

BackgroundEpidermal growth factor receptor (EGFR) represents a major target for current radiosensitizing strategies. We wished to ascertain whether a correlation exists between the expression of EGFR and treatment outcome in a group of patients with rectal adenocarcinoma who had undergone preoperative radiotherapy (RT).MethodsWithin a six-year period, 138 patients underwent preoperative radiotherapy and curative surgery for rectal cancer (UICC stages II-III) at our institute. Among them, 77 pretherapeutic tumor biopsies were available for semi-quantitative immunohistochemical investigation evaluating the intensity and the number (extent) of tumor stained cells. Statistical analyses included Cox regression for calculating risk ratios of survival endpoints and logistic regression for determining odds ratios for the development of loco-regional recurrences.ResultsMedian age was 64 years (range: 30–88). Initial staging showed 75% and 25% stage II and III tumors, respectively. RT consisted of 44-Gy pelvic irradiation in 2-Gy fractions using 18-MV photons. In 25 very low-rectal-cancer patients the primary tumor received a boost dose of up to 16 Gy for a sphincter-preservation approach. Concomitant chemotherapy was used in 17% of the cases. All patients underwent complete total mesorectal resection. Positive staining (EGFR+) was observed in 43 patients (56%). Median follow-up was 36 months (range: 6–86). Locoregional recurrence rates were 7 and 20% for EGFR extent inferior and superior to 25%, respectively. The corresponding locoregional recurrence-free survival rate at two years was 94% (95% confidence interval, CI, 92–98%) and 84% (CI 95%, 58–95%), respectively (P = 0.06). Multivariate analyses showed a significant correlation between the rate of loco-regional recurrence and three parameters: EGFR extent superior to 25% (hazard ratio = 7.18, CI 95%, 1.17–46, P = 0.037), rectal resection with microscopic residue (hazard ratio = 6.92, CI 95%, 1.18–40.41, P = 0.032), and a total dose of 44 Gy (hazard ratio = 5.78, CI 95%, 1.04–32.05, P = 0.045).ConclusionEGFR expression impacts on loco-regional recurrence. Knowledge of expression of EGFR in rectal cancer could contribute to the identification of patients with an increased risk of recurrences, and to the prediction of prognosis.

Pathological quality assurance in gastro-intestinal cancer

Quality assurance has become an integrated and important part of surgical pathology. Not only laboratory quality systems and quality control of pathology reporting have been introduced, also interdisciplinary quality systems are being developed. This review focuses on the different aspects of quality assurance that can nowadays be used in the daily practice of pathology management of gastrointestinal cancers, especially, gastric- and colorectal cancer. Own data are, especially, derived from the recently conducted clinical trial on pre-operative radiotherapy for rectal cancer and emphasize the importance of multidisciplinary approaches.