Preoperative Chemoradiotherapy For Rectal Cancer Research Articles

The influence of treatment response on the impact of resection margin status after preoperative chemoradiotherapy in rectal cancer.

505 Background: Circumferential resection margin (CRM) and distal resection margin (DRM) have different impact on clinical outcomes after preoperative chemoradiotherapy (CRT) followed by surgery. Effect and adequate length of resection margin as well as impact of treatment response after preoperative CRT was evaluated. Methods: Total of 403 patients with locally advanced rectal cancer underwent preoperative CRT followed by total mesorectal excision between January 2004 and December 2010. After applying the criterion of margin less than 0.5 cm for CRM and/or less than 1 cm for DRM, 158 cases were included as a study cohort. All patients underwent conventionally fractionated radiation with dose over 50 Gy and concurrent chemotherapy with 5-FU or capecitabine. Median follow-up duration was 44.9 months. Results: The 5-year overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were 83.3%, 75.6%, 86.3%, and 77.4% respectively. CRM of 1.5 mm and DRM of 7 mm were cutting points showing maximal difference using maximal chi-square method. In univariate analysis, the shorter CRM was significantly related with worse clinical outcomes, whereas DRM was not. In multivariate analysis, CRM of 1.5mm, ypN, and perineural invasion were prognosticators for OS, DFS, LRFS, and DMFS. CRM was not a significant prognostic factor for good responders, defined as patients with near total regression or T down-staging. However, poor responders demonstrated a significant difference according to the CRM status. Conclusions: Close CRM, defined as 1.5 mm, was a significant prognosticator, but the impact was different for treatment response. Postoperative treatment strategy may be individualized based on this finding. However, findings from this study needs to be validated with larger independent cohort. [Table: see text]

P3-151 - Preoperative Chemoradiotherapy for Lower Rectal Cancer with Severe Tumor Pain

ABSTRACT Preoperative chemoradiotherapy for rectal cancer aims to decrease the local recurrence after the surgery. This measure adopted as a standard treatment internationally, however various symptoms caused by tumor could obstruct the preoperative treatment because 10-12 weeks are required before surgery. Among them, tumor pain caused by the invasion into surrounding tissue could be a big and prolonged problem during the treatment. In four cases of lower rectal cancer complaining of severe anal pain on first admission, we planned preoperative chemoradiotherapy with supporting treatment including administration of NSAIDs with or without opioids. After 4 weeks of chemoradiotherapy, all the patients could reduce of the amounts of the drugs. After preoperative chemotherapy as planned, all of them had curative surgery consecutively. The preoperative chemoradiotherapy for oncological safety must be carried out with special interest, care and treatment on the anal pain caused by rectal cancer.

Oncologic Outcome After Preoperative Chemoradiotherapy in Patients With Pathologic T0 (ypT0) Rectal Cancer

Little is known about the oncologic outcomes of patients with ypT0 rectal cancer after preoperative chemoradiotherapy. To evaluate the clinicopathologic characteristics and oncologic outcomes of patients with ypT0 rectal cancer after preoperative chemoradiotherapy and curative radical surgery. This was a retrospective review of factors influencing outcome of patients treated with preoperative chemoradiotherapy for rectal cancer at a tertiary care university medical center in Seoul, Korea between 2000 and 2008. A total of 830 rectal cancer patients underwent surgery after preoperative chemoradiotherapy. Patients were included in the study if they had a pretreatment clinical classification of T3-4 or N+ (or T2N0 and preoperative chemoradiotherapy for sphincter preservation) and if they were classified on pathologic examination as ypT0 after preoperative CRT and curative radical surgery. Patients were classified as. Overall survival and disease-free survival were evaluated in relation to ypT0N0 or ypT0N1-2 status and other factors that might influence outcome. Of 91 patients included in the study, 54 (59.3%) were men; the mean patient age was 55 (SD, 11) years, and mean follow-up duration was 44 (SD, 23) months. Surgical procedures included low anterior resection in 68 patients, abdominoperineal resection in 21, and intersphincteric resection in 2. Mean tumor distance from the anal verge was 4.7 (SD, 1.8) cm. Of the 91 patients, 85 were classified as ypT0N0 and 6 as ypT0N1-2. No patient experienced local recurrence. A total of 11 patients (12.1%) had distant metastases, after a mean 11.1 months, including 7 (8.2%) with ypT0N0 and 4 (66.7%) with ypT0N1-2 tumors. One patient with ypT0N0 and 2 patients with ypT0N1-2 tumors died of metastasis. In patients classified as ypT0N0, the 5-year disease free survival and overall survival rates were 82.3% and 89.2%, respectively. Multivariate analysis showed that ypN1-2 status (p = 0.001) was a significant independent risk factor for recurrence (decreased 5-year disease-free survival), but no factor was associated with 5-year overall survival. The study is limited by its retrospective nature. Oncologic outcomes in patients with ypT0N0 rectal cancer were excellent. The presence of residual cancer cells in mesorectal lymph nodes represents a risk factor for distant metastasis.

352. Gene and MicroRNA Expression Predictive of Tumour Response in Patients Treated with Preoperative Chemoradiotherapy for Rectal Cancer

Background Preoperative chemoradiotherapy (pCRT) followed by surgery is the standard treatment for locally advanced rectal cancer (LARC). However, the response to pCRT is not uniform, and there is no effective method to predict tumour response to pCRT. Identification of patients not responsive to pCRT could avoid useless exposure to radiation or chemotherapy which is associated with adverse effects. Moreover, the identification of pathological complete response could select patients candidated to a more preserving surgery. The aim of this study is to investigate whether gene and micro-RNA (miRNA) expression profiling is associated with rectal cancer response to pCRT. Materials and methods Tissue biopsies were obtained from patients with mid-low LARC, before pCRT. All the patients underwent standard pCRT followed by resection. All surgical specimens underwent standardized histopathological examination. The biopsies with ≥50% of cancer tissue were considered for the experiment. Gene and miRNA expression was analyzed using one color microarrays technique (Agilent®), after RNA isolation. The data were normalized intra- and inter-array, filtered and then clustered. Gene and miRNA expression was compared between responders (R) and non responders (NR) as measured by histopathological tumour regression grade (TRG). Validation of microarrays data was made by quantitative PCR (qPCR). Results Thirty-eight patients, 16 (42%) R (TRG1-2) and 22 (58%) NR (TRG3-5), were considered. Using SAM (Significance Analysis of Microarrays) two class, 256 genes were found differentially expressed between NR and R (188 over- and 68 down-expressed). Performing PAM (Prediction Analysis for Microarray), 12 genes were strongly predictive of tumour response. Using SAM two class, 30 miRNAs were found differentially expressed between NR and R (24 over- and 6 down-expressed). Anti-correlation analyses, using MAGIA (miRNA and genes integrated analysis), revealed the same 8 miRNAs both in NR and R group, except for miR-630, over-expressed only in NR group. ABCC2 gene, miR-7, miR-182, miR-200a, miR-630, miR-638, and miR-1300 were validated by qPCR, confirming the data obtained by microarray analysis. Conclusions Pre-treatment gene and miRNA expression profiling may be helpful to predict response to pCRT in LARC. Further analyses to confirm these findings are required.

Lymph Node Retrieval after Preoperative Chemoradiotherapy for Rectal Cancer

BackgroundCurrent guidelines recommend the assessment of at least 12 lymph nodes for rectal cancer staging. Preoperative chemoradiotherapy may affect lymph node yield in this malignancy. This study investigated the impact of neoadjuvant chemoradiotherapy on the number of lymph nodes retrieved from rectal cancer patients. MethodsAn analysis of 162 rectal cancer patients who underwent curative surgery between 2005 and 2010. Seventy-one patients with stage II or III tumors received preoperative chemoradiotherapy. Using multivariate analysis, we assessed the correlation between clinicopathologic variables and number of retrieved lymph nodes. We also evaluated the association between survival and number of lymph nodes obtained. ResultsOn multivariate analysis, preoperative chemoradiotherapy was the only variable to independently affect the number of lymph nodes obtained. The mean number of lymph nodes was 14.2 in patients treated with preoperative chemoradiotherapy and 19.4 in those not treated (P < 0.001). In the chemoradiotherapy group, 29.6 % of patients had fewer than 12 lymph nodes obtained compared with 9.9 % in the primary surgery group (P = 0.003). After chemoradiation, the number of retrieved lymph nodes was inversely correlated with tumor regression grade. Results showed that 5-year overall and disease-free survival were similar whether the patient had 12 or more nodes retrieved or not. ConclusionsPreoperative chemoradiotherapy reduces the lymph node yield in rectal cancer. The number of retrieved lymph nodes is affected by degree of histopathologic response of the tumor to chemoradiation. Thus, number of lymph nodes should not be used as a surrogate for oncologic adequacy of resection after neoadjuvant chemoradiotherapy for rectal cancer.

A single‐centre experience of chemoradiotherapy for rectal cancer: is there potential for nonoperative management?

The aim of the study was to assess the outcome of patients who received chemoradiotherapy (CRT) for locally advanced rectal cancer, specifically those with complete clinical response (CCR) and who were then managed nonoperatively with a 'Watch and Wait' follow-up protocol. A retrospective study was carried out of patients undergoing preoperative CRT for rectal cancer, conducted in a district general hospital managing rectal cancer through the multidisciplinary team process. Forty-nine patients received preoperative CRT over a 5-year period (2004-2009). Twelve (24%) were considered potentially to have had a complete response on MRI. Of these, six subsequently had clinical evidence of residual disease, leading to surgery (mean time to surgery, 24 weeks; range, 12-36 weeks). The remaining six had CCR, avoiding surgery (mean follow up, 26 months; range, 12-45 months), with all six patients disease free to date. A further six patients had complete pathological response (CPR) following surgery after comprehensive histopathological assessment of the specimen. In this consecutive series of patients with locally advanced rectal cancer treated with CRT, 12% demonstrated a CCR and have been actively managed conservatively, thereby avoiding surgery. With further improvements in diagnostic assessment of response to CRT, this figure may rise.

Increased CD133 expression after preoperative chemoradiotherapy in rectal cancers other than mucin-rich tumors

This study is to characterize the sequential change in CD133 expression after preoperative chemoradiotherapy (CRT) in rectal cancer and its impact on postoperative prognosis. Forty-one patients with rectal cancer who had received CRT before surgery were selected retrospectively. In each case, immunohistochemical analysis was performed to compare CD133 expression in biopsy specimens taken before and after CRT. After CRT, CD133 expression was significantly increased in 14 (34%) patients, mildly increased in 25 (61%), and decreased in 2 (5%). However, no mucin-rich tumors showed high CD133 expression before or after CRT (p < 0.001). Disease-free survival and overall survival were significantly poorer in patients with significantly increased CD133 (p = 0.049 and p = 0.038, respectively). Increased CD133 after CRT is a significant prognostic factor in rectal cancer patients treated with preoperative CRT and surgical resection. CD133 might be an essential cancer stem cell marker.

Short-term outcomes after laparoscopic surgery following preoperative chemoradiotherapy for rectal cancer

PurposeThe safety and the feasibility of performing laparoscopic surgery for rectal cancer after preoperative chemoradiotherapy (CRT) have not yet been established. Thus, the aim of this study was to evaluate the efficacy and the safety of laparoscopic rectal cancer surgery performed after preoperative CRT.MethodsWe enrolled 124 consecutive patients who underwent laparoscopic surgery for rectal cancer. Of these patients, 56 received preoperative CRT (CRT group), whereas 68 did not (non-CRT group). The patients who were found to have distant metastasis and open conversion during surgery were excluded. The clinicopathologic parameters were evaluated and the short-term outcomes were compared between the CRT and non-CRT groups.ResultsThe mean operation time was longer in the CRT group (294 minutes; range, 140 to 485 minutes; P = 0.004). In the non-CRT group, the tumor sizes were larger (mean, 4.0 cm; range, 1.2 to 8.0 cm; P < 0.001) and more lymph nodes were harvested (mean, 12.9; range, 0 to 35; P < 0.001). However, there was no significant difference between the two groups in time to first bowel movement, tolerance of a soft diet, length of hospital stay, and postoperative complication rate.ConclusionPerforming laparoscopic surgery for rectal cancer after preoperative CRT may be safe and feasible if performed by a highly skilled laparoscopic surgeon. Randomized controlled trials and long-term follow-up studies are necessary to support our results.

Clinical predictive factors of pathologic tumor response after preoperative chemoradiotherapy in rectal cancer

PurposeThe aim of this study was to identify clinical predictive factors for tumor response after preoperative chemoradiotherapy (CRT) in rectal cancer.Materials and MethodsThe study involved 51 patients who underwent preoperative CRT followed by surgery between January 2005 and February 2012. Radiotherapy was delivered to the whole pelvis at a dose of 45 Gy in 25 fractions, followed by a boost of 5.4 Gy in 3 fractions to the primary tumor with 5 fractions per week. Three different chemotherapy regimens were used (5-fluorouracil and leucovorin, capecitabine, or tegafur/uracil). Tumor responses to preoperative CRT were assessed in terms of tumor downstaging and pathologic complete response (ypCR). Statistical analyses were performed to identify clinical factors associated with pathologic tumor response.ResultsTumor downstaging was observed in 28 patients (54.9%), whereas ypCR was observed in 6 patients (11.8%). Multivariate analysis found that predictors of downstaging was pretreatment relative lymphocyte count (p = 0.023) and that none of clinical factors was significantly associated with ypCR.ConclusionPretreatment relative lymphocyte count (%) has a significant impact on the pathologic tumor response (tumor downstaging) after preoperative CRT for locally advanced rectal cancer. Enhancement of lymphocyte-mediated immune reactions may improve the effect of preoperative CRT for rectal cancer.

The Association Between Anal Function and Neural Degeneration After Preoperative Chemoradiotherapy Followed by Intersphincteric Resection

Preoperative chemoradiotherapy for rectal cancer is administered to improve local control, but it can also induce severe anal dysfunction after surgery. The goals of the study were to assess the influence of preoperative chemoradiotherapy on pathological findings and to examine the correlation of these findings with the cause of severe anal dysfunction after intersphincteric resection. Peripheral nerve degeneration was evaluated histopathologically with the use of hematoxylin and eosin-stained sections of surgical specimens after intersphincteric resection, based on karyopyknosis, vacuolar degeneration, acidophilic degeneration of cytoplasm, denucleation, and adventitial neuronal changes. Each item was scored to quantify the level of neural degeneration, and the relationship between degeneration and anal function was examined at 12 months after closure of the stoma. Anal function was assessed by questionnaire, and incontinence was evaluated based on the Wexner score. This study was conducted at the National Cancer Center Hospital East from 2001 to 2006. The subjects were 68 patients with lower rectal cancer who underwent intersphincteric resection with (n = 47) or without (n = 21) preoperative chemoradiotherapy. The findings in the 2 groups were compared to clarify the association between the degree of histological degeneration and postoperative anal function. Neural degeneration was significantly higher in the chemoradiotherapy group, and the neural degeneration and Wexner scores had a significant correlation (P = .003, r = 0.477). Preoperative chemoradiotherapy induced marked neural degeneration around the rectal tumor. The significant correlation between the degeneration score and postoperative anal function suggests that this score may be a useful marker to predict the influence of preoperative chemoradiotherapy on anal function after surgery.

Factors associated with use of preoperative chemoradiotherapy for rectal cancer.

e14079 Background: Studies of patients with stage II/III rectal cancer have demonstrated that preoperative (preop) chemoradiotherapy (CRT) improves local control, reduces toxicity and is associated with more sphincter preserving surgeries than postoperative (postop) CRT. While preop CRT has been recommended as the standard of care, many still receive postop CRT. We determined the proportion and associated characteristics of those who received preop CRT among our sample. Methods: We identified patients with stage II/III rectal cancer who had primary site resection and CRT in the population-based cohort studied by the Cancer Care Outcomes Research and Surveillance Consortium, and used data from patient surveys and abstracted medical records to construct patient variables (age, gender, marital status, race, education, income, insurance status, stage, comorbidity, patient treatment preferences, research site, types and sequence of providers seen) and determine sequence of CRT and surgery. Multivariable logistic regression was used to model the association between predictors and receipt of preop CRT. Results: Of the 220 patients meeting inclusion criteria, 64% received preop CRT and 36% received postop CRT. A multivariate model showed those visiting a medical oncologist (MO) or radiation oncologist (RO) prior to receiving any treatment had a 91% (95% CI, 86% to 97%) probability of receiving preop CRT, whereas those who did not had a 30% (95% CI, 19% to 41%) probability. Subjects visiting a RO prior to a surgeon had a 91% (95% CI, 79% to 100%) probability of receiving preop CRT, whereas those visiting a surgeon first had a 65% (95% CI, 57% to 73%) probability. No other patient characteristics remained significant in the multivariate model. Conclusions: Early visits to an oncologist and sequencing of provider visits appear to be more important predictors of receiving preop CRT than the extensive list of patient characteristics evaluated in this study. Further evaluation of provider characteristics, referral patterns and health system processes that determine treatment should be undertaken to help design targeted interventions to reduce variation from recommended care.

A Case of Marked Response to Preoperative Chemoradiotherapy for Rectal Cancer With Para-Aortic Lymph Node Metastasis

A 67-year-old man had rectal cancer with para-aortic lymph node metastasis. Prior to surgical resection, tegafur-uracil and leucovorin had been administered orally as chemotherapy, and radiotherapy (50.4 Gy) was applied for the rectum and para-aortic lymph nodes. Low anterior resection was then performed, followed by 45 cycles of chemotherapy in total. Enlargement of the left axillary lymph nodes was noted during treatment, but nodes shrank in response to treatment with bevacizumab + FOLFIRI (i.e., irinotecan + 5-fluorouracil/leucovorin). As of the time of writing, 36 months after diagnosis, no swelling of the para-aortic lymph nodes was evident and chemotherapy was being continued. This patient was alive after achieving response to neoadjuvant therapy comprising chemotherapy and irradiation of the para-aortic lymph nodes, along with postoperative chemotherapy. This therapeutic approach of preoperative chemotherapy plus irradiation of the primary lesion and para-aortic lymph nodes has potential as an effective treatment.

Circulating Cell-Free DNA: A Promising Marker of Pathologic Tumor Response in Rectal Cancer Patients Receiving Preoperative Chemoradiotherapy

The circulating cell-free DNA (cfDNA) in plasma has been reported to be a marker of cancer detection. The aim of this study was to investigate whether the cfDNA has a role as response biomarker in patients receiving preoperative chemoradiotherapy (CRT) for rectal cancer. Sixty-seven patients (median age 61years; male/female 42/25) who underwent CRT for rectal cancer were evaluated. After tumor regression grade (TRG) classification was made, the patients were classified as having disease that responded (TRG 1-2) and that did not respond (TRG 3-5) to therapy. Plasma samples were obtained from patients before and after CRT. The cfDNA levels were analyzed by quantitative real-time polymerase chain reaction of β-globin. On the basis of the Alu repeats, the cfDNA was considered as either total (fragments of 115bp, Alu 115) or tumoral (fragments of 247bp, Alu 247). The association between the pre- or post-CRT levels and between variations during CRT of the Alu 247, Alu 115 repeat, and Alu 247/115 ratio (cfDNA integrity index) and the pathologic tumor response was analyzed. The baseline levels of cfDNA were not associated with tumor response. The post-CRT levels of the cfDNA integrity index were significantly lower in responsive compared to nonresponsive disease (P=0.0009). Both the median value of the Alu 247 repeat and the cfDNA integrity index decreased after CRT in disease that responded to therapy (P<0.005 and P<0.005, respectively) compared to disease that did not respond to therapy (P=0.83 and P=0.726, respectively). The results of the multivariable logistic regression analysis showed that only the cfDNA integrity index was significantly and independently associated with tumor response to treatment. The plasma levels of the longer fragments (Alu 247) of cfDNA and the cfDNA integrity index are promising markers to predict tumor response after preoperative CRT for rectal cancer.

Prognostic Significance of Tumor Regression Grade after Preoperative Chemoradiotherapy for Rectal Cancer

Prognostic Significance of Tumor Regression Grade after Preoperative Chemoradiotherapy for Rectal Cancer

The Metabolic Response using 18F-fluorodeoxyglucose Positron Emission Tomography and Carinoembryonic Antigen as a Predictive Factor of Tumor Response to Preoperative Chemoradiotherapy in Rectal Cancer

The Metabolic Response using 18F-fluorodeoxyglucose Positron Emission Tomography and Carinoembryonic Antigen as a Predictive Factor of Tumor Response to Preoperative Chemoradiotherapy in Rectal Cancer

Prediction of Response to Preoperative Chemoradiotherapy in Rectal Cancer by Multiplex Kinase Activity Profiling

Tumor response of rectal cancer to preoperative chemoradiotherapy (CRT) varies considerably. In experimental tumor models and clinical radiotherapy, activity of particular subsets of kinase signaling pathways seems to predict radiation response. This study aimed to determine whether tumor kinase activity profiles might predict tumor response to preoperative CRT in locally advanced rectal cancer (LARC). Sixty-seven LARC patients were treated with a CRT regimen consisting of radiotherapy, fluorouracil, and, where possible, oxaliplatin. Pretreatment tumor biopsy specimens were analyzed using microarrays with kinase substrates, and the resulting substrate phosphorylation patterns were correlated with tumor response to preoperative treatment as assessed by histomorphologic tumor regression grade (TRG). A predictive model for TRG scores from phosphosubstrate signatures was obtained by partial-least-squares discriminant analysis. Prediction performance was evaluated by leave-one-out cross-validation and use of an independent test set. In the patient population, 73% and 15% were scored as good responders (TRG 1-2) or intermediate responders (TRG 3), whereas 12% were assessed as poor responders (TRG 4-5). In a subset of 7 poor responders and 12 good responders, treatment outcome was correctly predicted for 95%. Application of the prediction model on the remaining patient samples resulted in correct prediction for 85%. Phosphosubstrate signatures generated by poor-responding tumors indicated high kinase activity, which was inhibited by the kinase inhibitor sunitinib, and several discriminating phosphosubstrates represented proteins derived from signaling pathways implicated in radioresistance. Multiplex kinase activity profiling may identify functional biomarkers predictive of tumor response to preoperative CRT in LARC.

Preoperative chemoradiotherapy for rectal cancer: a comparison between intravenous 5‐fluorouracil and oral capecitabine

Capecitabine provides an attractive alternative to intravenous (IV) 5-flourouracil (5-FU) in chemoradiation regimes for rectal cancer by avoiding the need for intravenous access and inpatient stay. We aimed to compare retrospectively the efficacy of concurrent capecitabine with IV 5-FU in preoperative pelvic chemoradiation schedules for rectal cancer in our centre. Patients treated from January 2005 to June 2007 were included. Information was collected on patient characteristics; treatment details; pathological response to treatment; recurrence and survival. All statistical analyses were performed using SPSS V17. All patients had pelvic radiation. Ninety-nine patients were treated with capecitabine and 97 with 5-FU. The two groups were well matched for age, sex and TNM stage. There were significantly more PS (performance status) 0 patients in the capecitabine group (51%vs 30%) (P = 0.001). Of the 99 patients in the capecitabine group, 91 (92%) were able to undergo surgery with 84 (93%) achieving R0 resection. In the 5-FU group, these proportions were 87 (90%) and 70 (80%). The difference in the rate of R0 resection was statistically significant (P = 0.024). The APR rate was 35% in the capecitabine group compared with 47% in the 5-FU group (P = 0.06). There was no significant difference in pathological complete response (pCR) rates between capecitabine (14%) and 5-FU(12%). A higher pCR rate (30%) was observed in patients who underwent a brachytherapy boost (P = 0.051). There were three local recurrences in the whole patient group, (capecitabine 1; 5-FU 2). Thirty-five patients had distant metastases, 14 in the capecitabine and 21 in the 5-FU group. There was no significant difference in the risk of recurrence between the two groups. Six patients in each group had grade 3 toxicity with diarrhoea being more common with capecitabine. Preoperative chemoradiotherapy with capecitabine for rectal cancer is efficacious and comparable to 5-FU (IV). It is more convenient, is well tolerated and avoids the need for inpatient admission.

The use of FDG-PET/CT and diffusion-weighted magnetic resonance imaging for response prediction before, during and after preoperative chemoradiotherapy for rectal cancer

Purpose. To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusion-weighted magnetic resonance imaging (DW-MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. Material and methods. Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and five weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUVmax) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coefficients (ADC) were determined. The ΔSUVmax during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision (TME). Results. ΔSUVmax during and after CRT significantly correlated with the pathological response to treatment (during CRT: ΔSUVmax = 59% ± 12% for pCR vs. 25% ± 27% if no pCR, p=0.0036; post-CRT: 90% ± 11 for pCR vs. 63% ± 22 if no pCR p=0.013). ROC curve analysis revealed an optimal threshold for ΔSUVmax of 40% during CRT and 76% after CRT. The initial ADC value was also significantly correlated with pCR (0.94 ± 0.12 × 10−3 mm2/s for pCR vs. 1.2 ± 0.24 × 10−3 mm2/s, p=0.002) and ROC curve analysis revealed an optimal threshold of 1.06 × 10−3 mm2/s. Combining the provided ΔSUVmax thresholds during and after CRT increased specificity of the prediction (sensitivity 100% and specificity 94%). The combination of the thresholds for the initial ADC value and the ΔSUVmax during CRT increased specificity of the prediction to a similar level (sensitivity of 100% and specificity of 94%). Conclusions. The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT.

Mandard tumor regression grade as a prognostic factor following preoperative chemotherapy/radiotherapy for locally advanced rectal cancer.

e14024 Background: To assess the prognostic value of the Mandard tumour regression score (TRG) following preoperative chemo/radiotherapy in patients with locally advanced rectal cancer. Methods: The study involved 94 patients with locally advanced rectal cancer treated with preoperative chemo/radiotherapy at Nottingham University Hospital between April 2001 and December 2005. Patients were treated with CT planned radiotherapy to a dose of 50 Gy in 25 fractions over 5 weeks with or without concurrent capecitabine chemotherapy at a dose of 1,650 mg/m2/day. Surgery was performed after an interval of 6-10 weeks. The response to preoperative treatment was carefully graded by a single pathologist using the five point Mandard tumour regression grade (TRG). The median follow-up was 40 months (range 3-90 months). Results: Of the 94 patients 11% were TRG1, 39% were TRG2, 33% were TRG3, 16% were TRG4 and 1% were TRG5. In view of the small numbers in TRG4 and TRG5, the groups were combined into TRG1, TRG2 and TRG3-5 to simplify further analysis. The Mandard score was clearly related to both disease free (p = 0.001) and overall survival (p = 0.023) on Kaplan Meier analysis. The 5 year disease free and overall survival rate for patients with a complete response (TRG1) was 100%. Conclusions: The Mandard tumour regression score is a strong prognostic factor and predicts for long-term outcome following preoperative chemoradiotherapy in rectal cancer. The agreement of a reliable consistent method to evaluate tumour regression remains a clinical priority. No significant financial relationships to disclose.

Prospective assessment of imaging after preoperative chemoradiotherapy for rectal cancer

The aim of the study was to assess the accuracy of imaging techniques in predicting pathologic tumor (ypT), node (ypN) stages and the circumferential resection margin (ypCRM) status of rectal cancers after preoperative chemoradiotherapy (CRT). Using pelvic computed tomography (CT), magnetic resonance imaging (MRI), and endorectal ultrasound (ERUS), 90 consecutive patients with locally advanced mid-to-low rectal cancer were prospectively assessed. Postirradiation T and N stages and infiltration of the CRM, as assessed by CT, MRI and ERUS, were compared with histopathologic findings. The accuracy of ypT staging was low, whatever the imaging technique used (37% by CT, 34% by MRI, and 27% by ERUS), the most frequent inaccuracy being overstaging. Imaging showed a good specificity and good negative predictive values (NPV) when mural staging was grouped into ypT ≤ 3 and ypT4 categories; in particular, ERUS achieved a 92% specificity and 95% NPV. CRM involvement was correctly predicted in 71% of patients by CT (74% specificity; 93% NPV) and in 85% by MRI (88% specificity; 95% NPV). The accuracy for nodal staging was 62%, 68%, and 65% by CT, MRI and ERUS, respectively; the corresponding NPV were 88%, 78%, and 76%. Current imaging techniques are inaccurate in restaging rectal cancer after CRT but are useful in predicting T ≤ 3 tumors, cases with negative nodes and tumor-free CRM. These findings may be of clinical relevance for planning less invasive surgery.