Rectal Cancer Regression Grade Research Articles

Response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy.

To determine the response of various histological types of locally advanced rectal cancer to neoadjuvant multimodality therapy. The non-randomised, quasi-experimental retrospective cohort study was conducted at the Combined Military Hospital, Rawalpindi, Pakistan, and comprised data of patients treated between January 1, 2020, to September 30, 2021. The data retrieved related to histologically proven and locally advanced rectal cancer patients aged 18-70 years receiving neoadjuvant chemoradiotherapy. Radiotherapy dose was 45 gray to pelvis with a boost to gross tumour of 5.4 gray in 3 fractions by using volumetric arc therapy concurrently with capecitabine 625mg/m² daily. A magnetic resonance imaging scan of pelvis with contrast was done at 5-10 weeks before surgery. Histological response to neoadjuvant treatment of various histological types was evaluated using the Rectal Cancer Regression Grade. Data was analysed using SPSS 22. Of the 182 patients evaluated, 108(59.34%) were included; 64(59.3%) males and 44(40.7%) females. The overall mean age was 45.4±5.2 years. Regression status was grade 1 in 24(22%) patients, grade 2 in 43(40%) and grade 3 in 41(38%) (p=0.074). There were 12(11.11%) patients with signet ring cell and 10(83.3%) showed pathological tumour regression. There were 17(15.74%) patients with mucinous variant, and 12(70.5%) had tumour regression. There were 79(73.15%) patients with adenocarcinoma, and 59(74.6%) of them showed tumour regression. . There was less tumour regression in mucinous and signet ring cell variants of adenocarcinoma. Modification and intensification of neoadjuvant therapy may be required in such histologies.

Artemis as Predictive Biomarker of Responsiveness to Preoperative Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer.

The aim of this study was to identify Artemis as a predictive biomarker for guiding preoperative chemoradiotherapy in locally advanced rectal cancer. The resection specimens were collected from 50 patients with rectal cancer who underwent preoperative chemoradiotherapy. Artemis expression in biopsy tissues was evaluated using immunohistochemical staining according to the percentage of positively stained cells combined with staining intensity. Among the 50 patients, 36 (72%) had a weakly positive Artemis protein expression, 10 (20%) had a moderately positive expression, and 4 (8%) showed a strongly positive expression. The criteria of magnetic resonance imaging tumor regression grade (mrTRG) and pathological rectal cancer regression grade (RCRG) were used to assess the tumor response to chemoradiotherapy. Correlation analysis shows that there is a significant negative correlation between high Artemis immunoscore and treatment response (r = -0.532, p < 0.001). The results imply that high Artemis expression was associated with poor treatment response. Our study suggested a potential role of Artemis as a predictive biomarker of the tumor response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer.

Dual energy CT − a possible new method to assess regression of rectal cancers after neoadjuvant treatment

The measurement of tumor regression after neoadjuvant oncological treatment has gained increasing interest because it has a prognostic value and because it may influence the method of treatment in rectal cancer. The assessment of tumor regression remains difficult and inaccurate with existing methods. Dual Energy Computed Tomography (DECT) enables qualitative tissue differentiation by simultaneous scanning with different levels of energy. We aimed to assess the feasibility of DECT in quantifying tumor response to neoadjuvant therapy in loco-advanced rectal cancer. We enrolled 11 patients with histological and MRI verified loco-advanced rectal adenocarcinoma and followed up on them prospectively. All patients had one DECT scanning before neoadjuvant treatment and one 12 weeks after using the spectral imaging scan mode. DECT analyzing tools were used to determine the average quantitative parameters; effective-Z, water- and iodine-concentration, Dual Energy Index (DEI), and Dual Energy Ratio (DER). These parameters were compared to the regression in the resection specimen as measured by the pathologist. Changes in the quantitative parameters differed significantly after treatment in comparison with pre-treatment, and the results were different in patients with different CRT response rates. DECT might be helpful in the assessment of rectal cancer regression grade after neoadjuvant treatment.

Significance of Anemia in Outcomes After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

BackgroundApproximately one quarter of patients receiving neoadjuvant chemoradiotherapy (NCRT) for locally advanced rectal cancer will be anemic at presentation. The outcomes of these anemic patients have historically been less favorable. We assessed the potential of anemia to act as an independent biomarker for a poor prognosis in patients with locally advanced rectal cancer. Materials and MethodsWe performed a retrospective, observational study of consecutive patients with locally advanced rectal adenocarcinoma who underwent NCRT from 2004 to 2009 at 3 English National Health Service trusts. The main outcomes were Rectal Cancer Regression Grade, mortality rate, and disease-free survival. These were compared between the anemic and nonanemic patients. ResultsA total of 273 patients were included. Of these patients, 63 (23%) had a hemoglobin level of < 120 g/L (anemic) at presentation. The Rectal Cancer Regression Grades were higher (less regression) in the anemic patients than in the nonanemic patients (χ2 = 10.14; P = .006). A subgroup analysis stratified by disease stage at presentation demonstrated less tumor regression in anemic patients with Dukes stage C disease (Dukes stage B, χ2 = 4.31, P = .12; Dukes stage C, χ2 = 5.36, P = .07). After adjusting for age, gender, and initial Dukes stage, the anemic patients demonstrated greater mortality rates than the nonanemic patients (hazard ratio, 1.73; 95% confidence interval, 1.05-2.86). The consistency with which the 2 independent reviewers were able to generate the rectal cancer regression grades from the historic pathology reports varied. Also, the subgroup analyses in the present study were often limited by low power. ConclusionThe present large UK study examined patients receiving NCRT for magnetic resonance imaging-proven, locally advanced rectal adenocarcinoma. Our findings have demonstrated that patients who were anemic at presentation have higher regression grades (less regression) in response to the treatment than nonanemic patients. This trend appeared to persist despite radiologic disease stage at presentation. Anemia at presentation was also associated with increased mortality rates compared with that of nonanemic patients.

Efficacy of neoadjuvant chemoradiotherapy combined with surgery for rectal mucinous adenocarcinoma

Objective To explore the efficacy of neoadjuvant chemoradiotherapy (NACRT) combined with surgery for rectal mucinous adenocarcinoma. Methods The retrospective cohort study was conducted. The clinical data of 313 patients with locally advanced rectal carcinoma who underwent NACRT combined with surgery at the Fujian Medical University Union Hospital between January 2008 and December 2013 were collected. Among the 313 patients, 32 and 281 patients were respectively allocated into the mucinous adenocarcinoma (MA) group and non-mucinous adenocarcinoma (NMA) group. Irradiation range included primary rectal lesion and pelvic lymph drainage, the upper bound is the fifth lumbar vertebra lower edge, both sides beyond true pelvic brim 1.5 cm, and the lower bound is the anus verge. Chemotherapy regimens included fluorouracil capecitabine and capecitabine combined with oxaliplatin. Operation was carried out after 6-8 weeks at the end of radiation according to the standard of total mesorectal excision (TME). Postoperative chemotherapy was conducted using the same preoperative regimen for 6 months. Observation indicators: (1) the sensitivity comparison of NACRT between the 2 groups [ypTNM stage, T downstaging, N downstaging, pathological complete response (PCR), rectal cancer regression grade (RCRG)] ; (2) long-term outcomes comparison after neoadjuvant chemoradiotherapy between the 2 groups. Follow-up using telephone interview, correspondence and outpatient examination was conducted once every 3 months within postoperative 2 years, once every 6 months at postoperative 3 years and once every year at postoperative 4 years up to June 30, 2015 and the end of follow-up (tumor recurrence and metastasis or death). Follow-up included physical examination, carcinoembryonic antigen (CEA) and CA19-9 test, chest X-ray and hepatic ultrasound and colonoscopy. Chest computed tomography (CT) and abdominal magnetic resonance imaging (MRI) or bone emission computed tomography (ECT) were conducted and PET/CT was conducted when necessary. Measurement data with normal distribution were represented as ±s, and comparison between groups was analyzed using an independent sample t test. Measurement data with skewed distribution were represented as M (range). Ordinal data were analyzed by the Mann-Whitney U test. Comparisons of count data were done using chi-square test. The Kaplan-Meier method was used to draw the survival curve and assess survival rate. The Log-rank test was used to compare survival. Results (1) The sensitivity comparison of NACRT between MA and NMA groups: number of patients in stage ypTNM 0, Ⅰ, Ⅱ and Ⅲ was 2, 5, 12, 13 in the MA group and 56, 65, 77, 83 in the NMA group, respectively, with a statistically significant difference between the 2 groups (Z=4.845, P 0.05). (2) The long-term outcomes comparison after neoadjuvant chemoradiotherapy between the 2 groups: 259 patients were followed up for a median time of 39 months (range, 6-90 months), 54 were dead and 72 had tumor recurrence or metastasis. The 3-year overall survival rate and 3-year tumor-free survival rate were 82.3%, 73.8% in the MA group and 84.4%, 78.0% in the NMA group, respectively, with no statistically significant difference between the 2 groups (χ2=0.399, 0.359, P>0.05). Conclusion The NACRT combined with surgery for rectal cancer has also benefited mucinous rectal carcinoma, and it is equivalent in the overall survival of patients with non-mucinous adenocarcinoma. Key words: Rectal neoplasms; Mucinous adenocarcinoma; Neoadjuvant therapy; Multivariate analysis

Value of percent change in tumoral volume measured at T2 -weighted and diffusion-weighted MRI to identify responders after neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinoma.

To evaluate the percent change in tumoral volume measured at T2 -weighted magnetic resonance imaging (T2 WMRI) and diffusion-weighted (DWI) as a method to identify responders after chemo- and radiation therapy (CRT) in patients with locally advanced rectal carcinoma. Forty-five consecutive patients (mean age ± SD: 72 years ± 9.7; male/female = 24/21) with locally advanced rectal carcinoma underwent CRT followed by surgery. Each patient underwent T2 WMRI and DWI at 1.5T before and 6 weeks after the completion of CRT. The percent change in tumoral volume before and 6 weeks after CRT was compared in patients classified as responders and nonresponders according to rectal cancer regression grade. Twenty-five patients were classified as responders with either partial (n = 20) or complete response (n = 5), while 20 patients were classified as nonresponders due to stable disease (n = 18) or disease progression (n = 2). Responders vs. nonresponders differed in the percent change of tumoral volume at T2 WMRI (-67% ± 26% vs. -29% ± 26%; P < 0.05) and DWI images (-72% ± 24% vs. -33% ± 28%; P < 0.05) with a cutoff ≤ -70% for T2 WMRI (sensitivity = 69%, 95% confidence interval [CI]: 48-85%; specificity = 100%, 95% CI 81-100%) and ≤66% for DWI (sensitivity = 73%, 95% CI: 52-88%; specificity = 100%, 95% CI 81-100%). The percent change in tumoral volume at T2 WMRI and DWI images can differentiate responders from nonresponders in patients with locally advanced rectal carcinoma after neoadjuvant CRT. J. Magn. Reson. Imaging 2016;44:1415-1424.

PWE-294 The significance of the rectal cancer regression grade (RCRG) in prognosis after neo-adjuvant chemoradiotherapy treatment of adenocarcinoma of the rectum

Introduction Complete pathological response is widely accepted to be an independent predictor for better prognosis after neo-adjuvant chemoradiotherapy treatment (NCRT) of locally-advanced adenocarcinoma of the rectum. 1 Less is known about the role of the Rectal Cancer Regression Grades (RCRGs) in predicting prognosis where partial tumour regression is seen. The aim of this study was to examine the relationship between RCRG and mortality in patients with locally-advanced adenocarcinoma of the rectum treated with NCRT. Method A retrospective study of all patients treated with NCRT for locally-advanced rectal cancer between 2004–2009 in 3 UK centres was undertaken. Data was collected from oncology, radiology and laboratory databases as well as patient records. Differences in mortality rates were compared for patients within the 3 different RCRG groups using univariate and multivariate analysis. The multivariate analysis adjusted for the known confounders of age, sex and stage of disease at presentation. A subset analysis was performed on patients with partial tumour regression by excluding those patients with a complete pathological response. Results Of 273 patients treated, 183 (67%) were male. Median follow up time was 3.60 years (2.58–4.99). Univariate analysis demonstrated an association between higher RCRGs and increased mortality with hazard ratios (HRs) for RCRG1:RCRG2 of 2.05 (95% CI 1.67–3.59) and RCRG1:RCRG3 of 3.25 (95% CI 1.82–5.82). This association persisted when multivariate analysis was performed, with HRs for mortality of RGRC1:RCRG2 2.12 (95% CI 1.20–3.74) and RCRG1:RCRG3 of 3.14 (95% CI 1.74–5.67). Fifty-five patients demonstrated a complete pathological response and were excluded from the analysis of patients with partial tumour regression. Of the remaining 218 patients, univariate analysis demonstrated a HR for mortality in RCRG1:RCRG2 of 1.40 (95% CI 0.77–2.56) and RCRG1:RCRG3 of 2.30 (95% CI 1.24–4.26). Multivariate analysis of mortality gave HRs of 1.52 (95% CI 0.82–2.81) and 2.38 (95% CI 1.27–4.45) respectively. Conclusion This study demonstrated an association between higher rectal cancer regression grades and an increased risk of mortality. This association, although weakened, appeared to persist amongst the subset of rectal cancer patients who only demonstrated partial tumour regression following chemoradiation. Disclosure of interest None Declared. Reference Maas M, Nelemans PJ, Valentini V, et al . Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44

Predictive factors and prognostic significance of tumor regression grade in rectal cancer.

739 Background: Several systems describe tumour regression grade (TRG) after neo-adjuvant chemo-radiotherapy (nCRT) in rectal cancer; however, there is lack of literature on factors predicting TRG and its prognostic significance when comparing two TRG systems. Methods: Chart review of 187 patients (pts) diagnosed with rectal cancer managed at our institution identified clinical T3 or T4 and/ or node positive adenocarcinoma who completed nCRT between 2005-2011. Assessment of TRG post-nCRT in 104 pts was determined using College of American Pathologists (CAP) and Modified Rectal Cancer Regression Grade (mRCRG) scoring systems. Logistic regression model was used to identify factors associated with TRG. Overall survival (OS) was estimated using Kaplan-Meier method, log-rank test to compare groups and Cox proportional hazard model to estimate hazard ratio. Results: Median age of 103 eligible pts was 64 (range [r] 31-88) and 70% were male. Median pre-nCRT tumour size was 4 cm (r 0.5-12). 61% tumours were distal. Radiation dose (RD) was &gt;54 Gy in 57%, 50.4 Gy in 40%, and 45 Gy in 3% patients. 71% received concomitant 5 FU; 12% capecitabine and 17% according to clinical trials prior to radical surgery. Median time between completion of nCRT and surgery was 49 days. CAP scoring was 0 (21%), 1 (7%), 2 (19%), and 3 (53%) whereas mRCRG scoring was 1 (31%), 2 (21%), and 3 (48%). With median follow up 5.04 years (yr), 5 yr OS was 65%. OS was 77% for CAP 0 and 1 vs. 59% for CAP 2 and 3 (p=0.0483, HR2.4); mRCRG 1 and 2 OS was 75% vs 54% for mRCRG 3 (p= 0.0060, HR2.6). &gt;30% reduction in pre-nCRT tumour occurred in 63% of CAP 1, 2, and 3 cases. Age (≥65 yr), higher RD and higher pre-op CEA were associated with mRCRG grade 3 (p=0.0339, 0.0415, and 0.0760 respectively). Tumour size, location, grade, type of chemotherapy, or gender were not predictive of TRG. Conclusions: Favorable TRG post-nCRT is associated with a statistically significant OS advantage. Younger age and RD escalation are associated with favorable TRG. CAP and mRCRG scoring systems of TRG were comparable for prognosis. nCRT leads to a significant cytoreduction in 63% of non-complete responders. TRG may have a future role in decisions on surgery, organ sparing, adjuvant chemotherapy, surveillance and patient counseling.

Pathological prognostic factors in locally advanced rectal carcinoma after neoadjuvant radiochemotherapy: analysis of 113 cases

Neoadjuvant radiochemotherapy (RCT) followed by surgical resection is the treatment for locally advanced mid-rectal or low rectal cancer. The aim of this study was to evaluate postoperative histological prognostic factors in a series of surgical specimens after neoadjuvant RCT. One hundred and thirteen patients were included. Macroscopic and microscopic examinations were performed according to CAP recommendations, with additional criteria such as tumour budding, the presence of calcifications, and response to neoadjuvant therapy assessed according to Modified Rectal Cancer Regression Grade (m-RCRG). The 3-year disease-free survival (DFS) was 67.6%. In univariate analysis, ypTN stage, tumour budding, circumferential margin, invaded margin and vascular and perineural invasion were prognostic factors. In multivariate analysis, the presence of calcifications (P=0.04) and an involved circumferential margin (P=0.03) were the only independent factors for worse DFS. mRCRG was not correlated with DFS. Among the 50 m-RCRG1 tumours, DFS was better in ypT0 patients than in other ypT stages (P=0.003). The presence of calcifications in the tumour bed is described for the first time as a prognostic factor in rectal cancer. The prognostic value of budding was demonstrated in this study after neoadjuvant RCT. ypT stage appears to be a more reliable predictor of oncological outcome than histological tumour regression grade, which needs to be standardized for better reproducibility.

Association between Anal Function and Therapeutic Effect after Preoperative Chemoradiotherapy followed by Intersphincteric Resection

Background/Aims: Preoperative chemoradiotherapy (CRT) for rectal cancer improves local control, but can also induce severe anal dysfunction after surgery. The goal of the study was to assess the relationship of the therapeutic effect of CRT with anal function and prognosis after intersphincteric resection (ISR). Methods: The subjects were 37 patients with lower rectal cancer who underwent ISR with preoperative CRT. The rectal cancer regression grade (RCRG) was quantified based on histologic features of surgical specimens. The relationships of RCRG with anal function (assessed by questionnaire) and incontinence (Wexner score) were examined at 12 months after surgery. Results: The median Wexner scores at 12 months after stoma closure in RCRG1, -2, and -3 cases were 18.0, 7.5, and 4.5, respectively, and anal function differed significantly among these groups (p = 0.001). Four cases had local recurrence, but 5-year local recurrence rates did not differ significantly among the groups. The 5-year disease-free survival rates were 88.9, 50.8, and 50.0% and the 5-year overall survival rates were 100, 77.3, and 66.7% in RCRG1, -2, and -3 cases, respectively, with no significant differences among the groups. Conclusion: Postoperative anal function is decreased when the effect of preoperative CRT is strong in patients treated with ISR.

Rectal cancer staging post neoadjuvant therapy – how should the changes be assessed?

To compare the utility and reproducibility of tumour regression grade scoring systems during histopathological assessment of rectal cancers resected after neoadjuvant (i.e. pre-operative) chemoradiotherapy. The histopathological features of tumour regression were assessed independently in 54 rectal cancer resection specimens using three scoring systems: the Tumour Regression Grade (TRG), modified Rectal Cancer Regression Grade (m-RCRG) and RCPath Cancer Dataset (RCPath) methods. Good interobserver agreement was achieved for all three systems (kappa scores: TRG system 0.719, m-RCRG system 0.734, RCPath system 0.742). Both observers diagnosed complete tumour regression and little/no regression in 11 cases (20% of all cases) and four cases (11% of all cases), respectively. A mean of 5.6 tumour blocks/case were taken and the mean lymph node yield was 8.4/case. All three scoring systems were usable in a diagnostic setting. The clinical significance of differing degrees of tumour regression is not yet universally agreed and, with this in mind, the m-RCRG system provided the optimum balance between applicability and the accurate recording of low, moderate and high degrees of tumour regression, thus facilitating future clinicopathological studies of moderate and high degrees of tumour regression and clinical outcome.

Magnetic resonance imaging predicts circumferential resection margin status in patients receiving preoperative chemoradiotherapy for rectal cancer

Objective: Accurate tumour re‐assessment after down‐sizing preoperative chemoradiotherapy (CRT) for locally advanced middle and lower rectal cancer provides valuable prognostic information prior to surgical resection. We assessed the accuracy of post‐CRT magnetic resonance imaging (MRI) in predicting circumferential resection margin status. The accuracy of MRI in staging chemoradiation down‐sized rectal tumours was also assessed.Method: Patients from a single tertiary referral centre who received preoperative CRT for biopsy‐proven rectal cancer between January 2003 and February 2005 were identified from a database. All patients received long‐course CRT (50Gy over 5 weeks and five‐fluorouracil/leucovorin) prior to surgery. A comprehensive MRI reporting proforma was completed for each patient and results were compared directly with histological specimens.Results: A total of 50 patients were eligible for the study. The overall accuracy for predicting circumferential resection margin status was 76% (38/50, P = 0.006, sensitivity = 96.9%, specificity = 73.8%, negative predictive value = 96.9%). For T staging MRI was accurate in 52% (26/50) and for nodal staging MRI was correct in 60% (30/50). Venous invasion was predicted in 66% (33/50, P = 0.04). A radiological rectal cancer regression grade was derived and this correlated with histological rectal cancer regression grade in 65% (32/49).Conclusion: This study demonstrates that post‐CRT MRI is accurate in predicting the circumferential resection margin status which provides useful prognostic information prior to surgery.

Magnetic resonance imaging predicts circumferential resection margin status in patients receiving preoperative chemoradiotherapy for rectal cancer

Objective: Accurate tumour re-assessment after down-sizing preoperative chemoradiotherapy (CRT) for locally advanced middle and lower rectal cancer provides valuable prognostic information prior to surgical resection. (1) We assessed the accuracy of post-CRT magnetic resonance imaging (MRI) in predicting circumferential resection margin status. (2) The accuracy of MRI in staging chemoradiation down-sized rectal tumours was also assessed. Method: Patients from a single tertiary referral centre who received preoperative CRT for biopsy-proven rectal cancer between January 2003 and February 2005 were identified from a database. All patients received long-course CRT (50 Gy over 5 weeks and 5-fluorouracil/leucovorin) prior to surgery. A comprehensive MRI reporting proforma was completed for each patient and results were compared directly with histological specimens. Results: Fifty patients were eligible for the study. The overall accuracy for predicting circumferential resection margin status was 76% (38/50, P = 0.006, sensitivity = 96.9%, specificity = 73.8%, negative predictive value = 96.9%). For T staging, MRI was accurate in 52% (26/50) and for nodal staging MRI was correct in 60% (30/50). Venous invasion was predicted in 66% (33/50, P = 0.04). A radiological rectal cancer regression grade was derived and this correlated with histological rectal cancer regression grade in 65% (32/49). Conclusion: This study demonstrates that post-CRT MRI is accurate in predicting the circumferential resection margin status, which provides useful prognostic information prior to surgery.

Growth hormone receptor overexpression predicts response of rectal cancers to pre-operative radiotherapy

In this study, we evaluated the possible role of Growth Hormone Receptor (GHR) expression pattern in determining rectal cancer radiosensitivity. We examined GHR expression in pre-treatment biopsy materials and post-operative specimens from 98 patients by immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR). GHR expression was evaluated for association with tumour radiosensitivity, which was defined according to Rectal Cancer Regression Grade (RCRG). IHC results demonstrated that GHR overexpression was significantly associated with a poor response to radiotherapy ( P < 0.001, r s = 0.399); RT-PCR detection of GHR expression on pre-radiation biopsy specimens also showed that GHR mRNA negative group had a higher radiation sensitivity ( P < 0.001, r s = 0.398). Compared with the pre-radiation biopsy specimens, the paired post-operative specimens showed a significantly up-regulated GHR expression in the reliquus cancer cells ( P < 0.001). In conclusion, GHR expression levels may be an indicator for rectal cancer radiosensitivity before pre-operative irradiation. The administration of GHR antagonist may have the potential to increase rectal cancer radiosensitivity.

Preoperative Chemoradiotherapy and Total Mesorectal Excision Surgery for Locally Advanced Rectal Cancer: Correlation With Rectal Cancer Regression Grade

Preoperative Chemoradiotherapy and Total Mesorectal Excision Surgery for Locally Advanced Rectal Cancer: Correlation With Rectal Cancer Regression Grade

Neoadjuvant Therapy for Rectal Cancer: Improved Tumor Response, Local Recurrence, and Overall Survival in Nonanemic Patients

Preoperative, long-course chemoradiotherapy is recommended for rectal cancers involving or threatening the mesorectal resection margin, but tumor response is variable. Some highly radiosensitive cancers completely regress, leading to reduced local recurrence and improved survival. This study was designed to evaluate the influence of anemia during chemoradiotherapy on tumor response, local and distant recurrence, and overall survival. Mean hemoglobins during chemoradiotherapy of consecutive patients with rectal cancer undergoing chemoradiotherapy and surgery were calculated and ranked. Anemia was defined as lowest quartile for males and females. Tumor response was histologically quantified using rectal cancer regression grade. Of 100 patients, 5 females and 20 males were anemic. Nonanemic patients achieved better tumor response (54 percent regression Grade 1) than anemic patients (28 percent, P = 0.028). There were more locally advanced cancers in anemic (48 percent T4) compared with nonanemic patients (21 percent T4), but radiologic T stage did not influence tumor response (50 percent T3 vs. 43 percent T4 regression Grade 1, P = 0.53) or overall survival. Mesorectal margin positivity was less in nonanemic (15 percent) compared with anemic patients (36 percent, P = 0.021). At median follow-up of 39 months, nonanemic patients (7 percent) suffered less local recurrence than anemic patients did (38 percent, P = 0.003). Overall survival at two years was improved in nonanemic (91 percent) compared with anemic patients (64 percent, P = 0.021), but was similar for T3 and T4 patients. Patients with normal hemoglobin during chemoradiotherapy achieved better tumor response, less local recurrence, and improved overall survival compared with anemic patients, independent of radiologic T stage. Correcting anemia before chemoradiotherapy might improve tumor response and oncologic outcomes.

Preoperative Chemoradiotherapy and Total Mesorectal Excision Surgery for Locally Advanced Rectal Cancer: Correlation With Rectal Cancer Regression Grade

Preoperative long-course chemoradiotherapy is recommended for rectal carcinoma when there is concern that surgery alone may not be curative. Downstaging of the tumor can be measured as rectal cancer regression grade (1-3) and may be of importance when estimating the prognosis. The aim of this study was to look at the long-term results of tumor regression in patients receiving long-course chemotherapy before surgical resection of rectal cancer. We reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinoma of the mid rectum or distal rectum found to be stage T3/4 between January 1995 and November 1999. Patients received 45 to 50 Gy irradiation in 2-Gy fractions and an infusion of 5-fluorouracil. Surgical specimens were assessed for rectal cancer regression grade. Patients were followed up routinely with clinical examination, computed tomography, and colonoscopy. Sixty-five patients with a mean age 65 (range, 32-83) years underwent chemoradiotherapy before surgical resection. Thirty patients (46 percent) were classified as rectal cancer regression Grade 1, with 9 patients (14 percent) having complete sterilization of the tumor. Fifty-three patients (82 percent) underwent a curative resection. Overall survival, with a median follow-up of 39 (range, 24-83) months, was 67 percent and was associated with tumor downstaging. The local recurrence rate was 5.8 percent in those patients who underwent a curative resection and was significantly lower with rectal cancer regression Grade 1 tumors (P = 0.03). Eight of nine patients (89 percent) whose tumor had been sterilized were alive and well with no recurrence of tumor at a median follow-up of 41 (range, 24-70) months. Preoperative chemoradiotherapy resulted in significant regression of tumor. Overall survival was high and was associated with downstaging of tumor. The local recurrence rate was significantly lower with rectal cancer regression Grade 1 tumors and was not seen in patients with sterilized tumors.

Histopathology of residual rectal carcinoma following preoperative radiochemotherapy

Preoperative radiotherapy with (CRT) or without chemotherapy (RT) in the management of patients with locally advanced rectal carcinoma is increasingly accepted as therapeutic modality to reduce local recurrence and improve survival, decrease tumor size and/or stage, has less toxicity compared to postoperative therapy, improves sphincter preservation and the ability to perform a curative resection. In a brief review of literature we discussed the possible prognostic role of most important pathologic parameters and their clinical implications. At present, predictive value of tumor response to neoadjuvant therapy remains uncertain, whether evaluated as five-point histological tumor regression grade (TRG) or recently proposed three-point rectal cancer regression grade (RCRG). However, most reports emphasize reduced local reccurence rates and disease-free survival advantage in patients with complete tumour regression or tumour down-staging, occuring in up to 20% and 60% of cases, respectively. Patients with advanced post-treatment tumour stage (ypT3/4), positive lymph nodes (ypN1/2), vascular invasion, positive circumferential resection margin, clearance < 2mm, or absence of tumor regression are shown to have poor clinical outcome. Among CRT-induced morphological features, only "fibrotic-type" stromal response with minimal inflammatory infiltrates and absence of surface ulceration are correlated to recurrence-free survival. Preliminary unpublished results of a pilot study from our multidisciplinary prospective trial relate to correlation of histopathologic parameters and morphologic changes to rectal cancer regression grade (RCRG). Therefore, we studied 22 consecutive patients, mean age 56 (range 23-69) years, with transmural cT3/4 stage and were subgrouped as follows: RCRG-1 (7 patients, 31.8%), RCRG-2 (9 patients, 40.,9%) and RCRG-3 (6 patients, 27,2%). In addition, 14 patients (63%) showed tumour downstaging and only 1 patient (4.5%) nodal down-staging after ypTNM restaging. There was the predominance of fibrotic-type stroma (16 patients, 72.8%) versus fibro-inflammatory response (6 patients, 27.2%), frequent tumoral necrosis (13 patients, 59%) but infrequent surface ulceration (5 patients, 22.7%) and peritumoural eosinophylic infiltration as well as endocrine cell differentiation (4 patients, 18%). The second aim of our study was to investigate determinants of radiosensitivity, i.e. the relationship between proliferative activity indices (Ki-67 and PCNA) as well as the induction of apoptosis (p53) and the tumour regression (RCRG) after neoadjuvant CRT. The interaction between Ki-67 and PCNA immunoexpression levels and the benefit of CRT was significant for Ki-67 (p = 0.03), but not for PCNA (p = 0.08) and p53 levels (p = 0.4). In a conclusion, high percentage of Ki-67-positive tumor cells in the preoperative biopsy predicts an decreased treatment response after preoperative CRT of rectal cancer. However, long-term follow-up and large studies are necessary to establish the value of regression grade and the need for its prediction by reliable biological markers.

Quantification of histologic regression of rectal cancer after irradiation: a proposal for a modified staging system.

Long-course preoperative radiotherapy has been recommended for rectal carcinoma when there is concern about the ability to perform a curative resection, for example, in larger tethered tumors or those sited anteriorly or near the anal sphincter. "Downstaging" of the tumor may occur, and this is of importance when estimating the prognosis and selecting postoperative therapy for patients. We studied the effects of preoperative chemoradiotherapy on the pathology of rectal cancer, and we propose a simplified measurement of tumor regression, the Rectal Cancer Regression Grade. We have reviewed those patients who received preoperative chemoradiotherapy followed by surgical resection for carcinomas of the mid or distal third of the rectum found to be Stage T3/4 on transrectal ultrasound or CT between January 1995 and December 1998. Patients received 45 to 50 Gy irradiation and an infusion of 5-fluorouracil. The surgical specimens were examined by one pathologist, and the Rectal Cancer Regression Grade was quantified. Forty-two patients, mean age 60 (range, 42-86) years, underwent chemoradiotherapy before surgery for rectal carcinoma. There were 28 anterior resections (67 percent; 9 with a colonic pouch), 12 abdominoperineal resections (27 percent), and 2 Hartmann's procedures (5 percent). Comparison of preoperative and pathologic staging revealed that the depth of invasion was downstaged in 17 patients (38 percent), and the status of involved lymph nodes was downstaged in 13 (50 percent) of 26 patients. Tumor regression was more than 50 percent (Rectal Cancer Regression Grades 1 and 2) in 36 patients (86 percent), with 7 patients (17 percent) having complete regression with absence of residual cancer cells. Significant tumor regression was seen in 86 percent of cases after chemoradiotherapy, with 19 patients showing a "good" responsiveness. We propose a modified pathologic staging system for irradiated rectal cancer, the Rectal Cancer Regression Grade, which includes a measurement of tumor regression. The utility of the proposed Rectal Cancer Regression Grade must be tested against long-term outcomes before its value in predicting prognosis and survival can be determined.