Pathological Circumferential Resection Margin Research Articles

Defining distal splenopancreatectomy by the mesopancreas.

The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

Postchemoradiation magnetic resonance imaging circumferential resection margin predicts treatment failure after multidisciplinary directed sphincter preservation in low rectal cancer.

This study aimed to review the magnetic resonance imaging (MRI) features of patients with low rectal cancer (LRC) undergoing preoperative chemoradiotherapy (CRT) and investigate the risk factors for treatment failure after sphincter preserving surgery following preoperative CRT based on multidisciplinary approach. Patients who underwent standard CRT and sphincter preserving radical surgery for LRC between January 2000 and December 2011 were retrospectively reviewed. Sphincter preservation failure (SPF) was defined as any one of the following: positive pathologic circumferential resection margin, local recurrence, failure to repair ileostomy, or permanent stoma formation due to anastomotic complications. Among the 191 patients, there were no overall significant differences between sphincter preservation success (n = 161) and SPF (n = 30) groups. SPF group showed a higher MRI circumferential resection margins (mrCRM) positive rate before and after CRT (before CRT: 33.3% vs. 16.1%, p = 0.027; after CRT: 23.3% vs. 6.2%, p = 0.002). Multivariate analysis showed that only mrCRM after CRT was associated with SPF (hazard ratio = 4.596, p = 0.005). SPF group showed worse 5-year cancer-specific survival (51% vs. 92.7%, p < 0.001). MRI-based assessment of the tumor after CRT plays a crucial role in predicting the success and feasibility of sphincter preservation as well as oncological outcomes in patients with LRC.

Predicting Positive Radial Margin on Restaging MRI of Patients with Low Rectal Cancer: Can We Do Better?

Objective The aim of this study was to characterize the tissue involving the margin and study if this information will affect margin prediction on restaging magnetic resonance imaging (MRI) in low rectal adenocarcinoma (LRC) patients treated with neoadjuvant long-course chemoradiotherapy (LCCRT). Methods In this retrospective study of nonmetastatic LRC (distal margin <5 cm from the anal verge) treated with LCCRT followed by surgery, a radiologist blinded to outcome reread the restaging MRI and documented if the radial margin was involved by tumor, fibrosis, or mucin reaction using T2 high-resolution (HR) and diffusion-weighted imaging (DWI). The diagnostic performance of tumor-involving margin on restaging MRI was assessed using surgical histopathology as a reference. Interobserver agreement between three independent radiologists was assessed in a subset. Results We included 133 patients (80 males and 53 females) with a mean (range) age of 44.7 (21-86) years and 82% of them had well or moderately differentiated adenocarcinoma. Baseline MRI showed T3 ( n = 58) or T4 ( n = 60) disease in 89% of the patients. The pathological margin was positive in 21% ( n = 28) cases. In restaging MRI, the circumferential resection margin (CRM) ≤1 mm in 75.1% ( n = 100) cases and MRI predicted tumor, fibrosis, and mucin reaction at the margin in 60, 34, and 6%, respectively, and histopathology showed tumor cells in 33, 14.7, and 16.6% of them, respectively. LRC with tumor-involving margin and bad response (MR tumor regression grade [mr-TRG] 3-5) on restaging MRI had fourfold increased risk of positive pathological circumferential resection margin (pCRM). There was moderate and fair inter-reader agreement for the tissue type involving the CRM ( κ = 0.471) and mr-TRG ( κ = 0.266), p < 0.05. The use of both distance criteria and tumor-involving margins improved the diagnostic accuracy for margin prediction from 39 to 66% on restaging MRI. Conclusions Margin prediction on restaging MRI can be improved by characterizing the tissue type involving the margin in low rectal cancer patients. The inter-reader agreement was moderate for determining the tissue type.

Preoperative computed tomography assessment of circumferential resection margin in retroperitonealized colon cancer predicts disease-free survival.

The aim of this retrospective study was to predict circumferential resection margin (CRM) involvement on preoperative CT, and prognostic impact of CRM assessment by CT (ctCRM) in patients with retroperitonealized colon cancer. This study included patients who underwent resection for ascending or descending colon cancer between July 2010 and February 2013. Positive ctCRM was defined as tumor distance to the retromesenteric plane of ≤ 1 mm. The origin of positive CRM was divided into primary tumor or other tumor components including lymph nodes, tumor deposits, or extramural venous invasions. Logistic regression analysis was performed to identify preoperative factors to predict pathologic CRM (pCRM). A Cox proportional hazards model was used in multivariable analysis to determine the preoperative factors affecting disease-free survival (DFS). A total of 274 patients (mean age, 64.0 years ± 11.0 [standard deviation]; 157 men) with retroperitonealized colon cancer were evaluated. Of 274 patients, 67 patients (24.5%) had positive CRM on surgical pathology. The accuracy of preoperative CT in predicting pCRM was 79.6% (218/274). Among preoperative factors, only CRM assessment on CT was independently associated with pCRM (p < 0.001). Positive ctCRM by primary tumor was an independent factor for DFS (HR, 3.362 [1.714-6.593]) and systemic recurrence (HR, 3.715 [1.787-7.724], but not for local recurrence on multivariable analyses. Preoperative CT can accurately predict pCRM, and positive ctCRM by primary tumor is an independent risk factor for DFS and systemic recurrence, but not for local recurrence in retroperitonealized colon cancer. • Preoperative CT can predict pathologic circumferential resection margin (CRM) with approximately 80% of accuracy in patients with retroperitonealized colon cancer. • Positive CRM by a primary tumor on preoperative CT is a poor prognostic factor for disease-free survival and systemic recurrence in patients with retroperitonealized colon cancer. • CRM involvement on CT was not associated with local recurrence in patients with retroperitonealized colon cancer.

Japanese multicenter prospective study investigating laparoscopic surgery for locally advanced rectal cancer with evaluation of CRM and TME quality (PRODUCT trial).

In Japan, we have not been able to validate the results of laparoscopic surgery for locally advanced rectal cancer using the universal index "circumferential resection margin (CRM)." Previously, we established a semi-opened circular specimen processing method and validated its feasibility. In the PRODUCT trial, we aimed to assess CRM in patients with locally advanced rectal cancer who underwent laparoscopic rectal resection. This was a multicenter, prospective, observational study. Eligible patients had histologically confirmed rectal adenocarcinoma located at or below 12 cm above the anal verge with clinical stage II or III and were scheduled for laparoscopic or robotic surgery. The primary endpoint was pathological CRM. CRM ≤1 mm was defined as positive. A total of 303 patients operated on between August 2018 and January 2020 were included in the primary analysis. The number of patients with clinical stage II and III was 139 and 164, respectively. Upfront surgery was performed for 213 patients and neoadjuvant therapy for 90 patients. The median CRM was 4.0 mm (IQR, 2.1-8.0 mm), and CRM was positive in 26 cases (8.6%). Univariate and multivariate analyses demonstrated that a predicted CRM from the mesorectal fascia of ≤1 mm on MRI was the significant factor for positive CRM (P=.0012 and P=.0045, respectively). This study showed the quality of laparoscopic rectal resection based on the CRM in Japan. Preoperative MRI is recommended for locally advanced rectal cancer to prevent CRM positivity.

Feasibility of the semi-opened method of specimen resection for a circumferential resection margin in rectal cancer surgery: a multicenter study.

A circumferential resection margin (CRM) > 1mm is a surrogate marker of oncologic outcomes in rectal cancer patients. In Japan, because the mesentery is removed from the rectum, the CRM cannot be measured. This multicenter prospective study evaluates the feasibility of a resected specimen processing method that allows CRM measurement. Fifty patients with rectal cancer were enrolled. Resected specimens were processed as previously reported. The primary outcomes were CRM measurement and the rate of CRM positivity. The secondary outcomes were the quality of total mesorectal excision, the possibility to visualize and sample the tumor, the number of harvested lymph nodes, and comparison between the pathological CRM and preoperative mesorectal fascia (MRF) involvement. This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry under identification number UMIN000031735. The CRM was measurable in all patients and found to be positive in three (6%). We confirmed tumor localization, sampled the tumor, and measured the distal margin in all patients. A median of 20 lymph nodes were harvested. The concordance rate between preoperative MRF involvement and pathological CRM status was 90%. A semi-opened rectal specimen with transverse slicing is a feasible method for measuring the CRM.

Outcomes of rectal cancer patients with a positive pathological circumferential resection margin.

Evidence-based management of positive pathological circumferential resection margin (pCRM) following preoperative radiation and an adequate rectal resection for rectal cancers is lacking. Retrospective analysis of prospectively maintained single-centre institutional database was done to study the patterns of failure and management strategies after a rectal cancer surgery with a positive pCRM. A total of 86 patients with rectal adenocarcinoma with a positive pCRM were identified over 8years (2011-2018). Majority had low-lying rectal cancers (90.7%) and were operated after preoperative radiotherapy (95.3%). Operative procedures included abdomino-perineal resections, inter-sphincteric resections, low anterior resections and pelvic exenteration in 61 (70.9%), 9 (10.5%), 11(12.8%) and 5 (5.8%) patients respectively. A total of 83 (96.5%) received chemotherapy as the sole adjuvant treatment modality while 2 patients (2.3%) were given post-operative radiotherapy and 1 patient underwent revision surgery. A total of 53 patients (61.6%) had recurrence, with 16 (18.6%), 20 (23.2%), 8(9.3%) and 9 (10.5%) patients having locoregional, systemic, peritoneal and simultaneous local-systemic relapse. Systemic recurrences were more often detected either by surveillance in an asymptomatic patient (20.1%) while local (13.1%) and peritoneal (13.2%) recurrences were more often symptomatic (p = 0.000). The 2-year overall survival (OS) and disease-free survival (DFS) of the cohort was 82.4% and 74.0%. Median local recurrence-free survival (LRFS) was 10.3months. Patients with a positive pCRM have high local and distal relapse rates. Systemic relapses are more often asymptomatic as compared to peritoneal or locoregional relapse and detected on follow-up surveillance. Hence, identification of such recurrences while still salvageable via an intensive surveillance protocol is desirable.

Impact of circumferential tumor location of mid to low rectal cancer on oncologic outcomes after preoperative chemoradiotherapy.

PurposeSome studies have suggested that circumferential tumor location (CTL) of rectal cancer may affect oncological outcomes. However, studies after preoperative chemoradiotherapy (CRT) are rare. This study aimed to evaluate the impact of CTL on oncologic outcomes of patients with mid to low rectal cancer who received preoperative CRT.MethodsPatients with mid to low rectal cancer who underwent total mesorectal excision after CRT from January 2013 to December 2018 were included in this retrospective study. The impact of CTL on the pathological circumferential resection margin (CRM) status, local recurrence-free survival (LRFS), disease-free survival (DFS), and overall survival (OS) was analyzed.ResultsOf the 381 patients, 98, 70, 127, and 86 patients were categorized into the anterior, posterior, lateral, and circumferential tumor groups, respectively. Tumor location was not significantly associated with the pathological CRM involvement (anterior, 12.2% vs. posterior, 14.3% vs. lateral, 11.0% vs. circumferential, 17.4%; P = 0.232). Univariate analyses revealed no correlation between CTL and 3-year LRFS (93.0% vs. 89.1% vs. 91.5% vs. 88%, P = 0.513), 3-year DFS (70.3% vs. 70.2% vs. 75.3% vs. 75.7%, P = 0.832), and 5-year OS (74.7% vs. 78.0% vs. 83.9% vs. 78.2%, P = 0.204). Multivariate analysis identified low rectal cancer and pathological CRM involvement as independent risk factors for all survival outcomes (all P < 0.05).ConclusionCTL of rectal cancer after preoperative CRT was not significantly associated with the pathological CRM status, recurrence, and survival.

Diagnostic Accuracy of CT for Evaluating Circumferential Resection Margin Status in Resectable or Borderline Resectable Pancreatic Head Cancer: A Prospective Study Using Axially Sliced Surgical Pathologic Correlation

ObjectiveCT plays a central role in determining the resectability of pancreatic cancer, which directs the use of neoadjuvant therapy. This study aimed to assess the diagnostic accuracy of CT in predicting circumferential resection margin (CRM) involvement in patients with resectable or borderline resectable pancreatic head cancer.Materials and MethodsSeventy-seven patients who were scheduled for upfront surgery for resectable or borderline resectable pancreatic head cancer were prospectively enrolled, and 75 patients (38 male and 37 female; mean age ± standard deviation, 68 ± 11 years) were finally analyzed. The CRM status was evaluated separately for the superior mesenteric artery (SMA) and posterior and superior mesenteric vein/portal vein (SMV/PV) margins. Three independent radiologists reviewed the preoperative CT images and evaluated the resection margin status. The reference standard for CRM status was pathologic examination of pancreaticoduodenectomy specimens in an axial plane perpendicular to the axis of the second portion of the duodenum. The diagnostic accuracy of CT was assessed for overall CRM involvement, defined as involvement of the SMA or posterior margins (per-patient analysis), and involvement of each of the three resection margins (per-margin analysis). The data were pooled using a crossed random effects model.ResultsForty patients had pathologically confirmed overall CRM involvement in pancreatic cancer, while CRM involvement was not seen in 35 patients. For overall CRM involvement, the pooled sensitivity and specificity were 15% (95% confidence interval: 7%–49%) and 99% (96%–100%), respectively. For each of the resection margins, the pooled sensitivity and specificity were 14% (9%–54%) and 99% (38%–100%) for the SMA margin, 12% (8%–46%) and 99% (97%–100%) for the posterior margin; and 37% (29%–53%) and 96% (31%–100%) for the SMV/PV margin, respectively.ConclusionCT showed very high specificity but low sensitivity in predicting pathological CRM involvement in pancreatic cancer.

Laparoscopic versus open resection in locally advanced rectal cancers: a propensity matched analysis of oncological and short-term outcomes.

The aim was to compare oncological and short-term outcomes between open and laparoscopic surgery in locally advanced rectal cancers. It is a retrospective analysis conducted in a high volume tertiary centre. Matching was carried out for nine variables, including preoperative factors, neoadjuvant treatment and sphincter preservation. Both the open and laparoscopic surgery arms had 239 patients each. The distributions of pretreatment MRI T3, T4, circumferential resection margin (CRM) positive tumours, neoadjuvant long-course chemoradiation and sphincter preservation were 80.3%, 13.6%, 50%, 89% and 56.4% respectively. The mean number of nodes harvested (12.9 vs. 12.7, P=0.716), pathological CRM positivity (6.3% in open vs. 5.4% in laparoscopic, P=0.697) and distal resection margins were similar. The mean blood loss was higher in open surgeries (910ml vs. 349ml, P<0.001). Anastomotic leaks and Clavien-Dindo Grade 3-4 complications were higher in the open arm than in the laparoscopy arm (5.9% vs. 1.7%, P=0.024, and 12.5% vs. 6.7%, P=0.015 respectively). The median postoperative hospital stay was significantly shorter in the laparoscopy arm (7 vs. 6, P=0.015). In CRM positive and threatened cases, the measured outcomes were similar between the two groups except for blood loss which was significantly higher in the open surgery (872 vs. 379, P=0.000). In high volume centres, in the hands of experienced colorectal surgeons, laparoscopic rectal surgery is oncologically safe in locally advanced rectal cancers and has lesser morbidity and shorter hospital stay than open surgery. In CRM positive and threatened cases the laparoscopic surgery showed less blood loss compared to open surgery, while other outcome measures were similar to open surgery.

Phase II trial of neoadjuvant mFOLFOX 6 with panitumumab (P) in T3 rectal cancer with clear mesorectal fascia (MRF) and KRAS, NRAS, BRAF, PI3KCA wild type (4WT). GEMCAD 1601 PIER trial.

3512 Background: Patients with advanced colorectal cancer with 4WT tumors achieve increased response rates with chemotherapy and anti-EGFR therapy as compared with chemotherapy alone. In clinically staged (c) T3 rectal cancer neoadjuvant oxaliplatin/fluoropyrimidine combination has shown to induce encouraging pathological complete response (pCR). We hypothesize that combining FOLFOX and P could improve outcomes in 4WT tumors. Methods: PIER was an investigator-initiated phase II, single-arm, multicentre clinical trial to evaluate the safety and efficacy of neoadjuvant mFOLFOX6 with P in pts &lt; 75-y, with 4WT rectal cancer of the middle third staged as T3 by centrally-reviewed magnetic resonance imaging (MRI) and clear MRF, who were candidate for a R0 resection with sphincter preservation surgery. Pts received 6 cycles and underwent re-staging with MRI and sigmoidoscopy. Pts without progression underwent total mesorectal excision 4 weeks after the last cycle. Patients with progression were treated with pre-op chemoradiotherapy. The primary endpoint was pCR. The study followed a 2-Stage Simon’s MiniMax design (P0 of 16%, P1 of 35%, alpha and beta of 0.1). The target sample size was 35 patients and if 9 or more achieved a pCR, the results would be compatible with efficacy. We present primary and early secondary endpoints. Results: Between 9/2017 and 6/2020, 90 patients were screened (56 excluded; 42 were excluded due to mutations, 12 were excluded due to discrepancies with central review of radiology) of whom 34 were enrolled. In the ITT population a pCR was observed in 11 pts (32.3%; [95% CI 17.39-50.53]) and a near-complete pathological response (Mandard 1+2) was observed 17 pts (52.9%). Clinical complete or near complete response was achieved in 50% and there were no progressions. R0 resection rate and pathological circumferential resection margin neg- were 100%. Full compliance with induction was 88%. Neoadjuvant G3/4 toxicity occurred in 54% and was consistent with FOLFOX/P safety profile. G3/4 postoperative related toxicity was 19% with one reoperation. Conclusions: The study met the threshold for efficacy. mFOLFOX6 with P as neoadjuvant therapy can be effective and safe without unexpected toxicities in mrT3, clear MRF and 4WT rectal cancer and resulted in a higher rate of pCR compared with our previous series (GEMCAD 0801; The Oncologist 2014) in a similar molecular-unselected population. This study was funded by Amgen S.A. Clinical trial information: NCT03000374.

Patterns of failure and outcomes of rectal cancer patients who had a positive pathological circumferential resection margin (pCRM)

Background: There is lack of data regarding the patterns of failure and outcomes after positive pathological circumferential resection margin (pCRM) resections in rectal cancer. Evidence based management strategies after positive pCRM resections are lacking.

Can Post-Treatment MRI Features Predict Pathological Circumferential Resection Margin (pCRM) Involvement in Low Rectal Tumors.

The MERCURY II study demonstrated the use of MRI-based risk factors such as extramural venous invasion (EMVI), tumor location, and circumferential resection margin (CRM) involvement to preoperatively predict pCRM (pathological CRM) outcomes for lower rectal tumors in a mixed group of upfront operated patients and patients who received neoadjuvant treatment. We aim to study the applicability of results of MERCURY II study in a homogeneous cohort of patients who received neoadjuvant chemoradiation (NACTRT) prior to surgery. After Institutional Review Board approval, post NACTRT restaging MRI of 132 patients operated for low rectal cancer between 2014 and 2018 were retrospectively reviewed by two radiologists for site of tumor, EMVI status, distance from anal verge (<4 or > 4cm), and mrCRM positivity. Findings were compared with post surgery pCRM outcomes using Fisher's exact test. Only 9/132(7%) patients showed pCRM involvement on histopathology, 8 of them being CRM positive on MRI (p= 0.01). The positive predictive value (PPV) of mrCRM positive status and pCRM status was 12.7% (95% CI: 9.7-16.5%), while the negative predictive value was 98.5% (95% CI: 91.4-99.8%) (p= 0.01). EMVI positive and anteriorly located tumors showed higher incidence of pCRM positivity but were not found to be significant (15% vs 5.2% and p= 0.13 and 8.6% vs 2.1% and p= 0.28, respectively). Unsafe mrCRM was the only factor significantly associated with pCRM positivity on post neoadjuvant restaging MRI. Tumors less than 4cm from anal verge, anterior tumor location, and mrEMVI positivity did not show statistically significant results to predict pCRM involvement.

Management of the positive pathologic circumferential resection margin in rectal cancer: A national cancer database (NCDB) study

BackgroundThe circumferential resection margin (CRM) is a primary predictor of local recurrence and survival in rectal cancer, and an important consideration in guiding treatment. CRM is usually predicted preoperatively, so optimal management of an unexpected pathologic positive CRM involvement is debatable. We aimed to investigate the postoperative management of T3N0 rectal cancers with a positive pathologic CRM, and the impact of each strategy on survival. MethodsThe NCDB was reviewed for pathological T3N0 rectal cancer cases from 2010 to 2015, that received neoadjuvant chemotherapy, had surgical resection with pathological clear margins, but a positive pathologic CRM(disease≤2 mm from radial margin). The main outcomes were the incidence, treatment modalities used, and impact of each modality on survival. Univariate analysis evaluated the demographic and provider characteristics across treatment groups. Kaplan-Meier and Cox regression analysis assessed survival and factors associated with overall survival (OS). ResultsOf 1607 cases with a positive CRM, 65% (1045) received no adjuvant treatment and 35% (n = 562) received adjuvant chemotherapy (AC). After matching, the 1-, 3-, and 5-year OS rates were 98.5%, 88.6% and 76.6% for AC and 96.9%, 84.6% and 68.4% for with no treatment (p = .027). Factors independently associated with improved OS were treatment at an academic/research facility (p = .009), minimally invasive approach (p = .005), well and moderately differentiated tumor (p < .001), absence of perineural invasion (p = .015) and AC administration (p = .047). ConclusionIn T3N0 rectal cancers resected with local clear margins but a positive pathologic CRM, AC improved OS. However, only a third received this option. Further study is needed to investigate the disparities in AC use in these patients with unexpected pathologic results.

MRI-Based Use of Neoadjuvant Chemoradiotherapy in Rectal Carcinoma: Surgical Quality and Histopathological Outcome of the OCUM Trial.

Preoperative magnetic resonance imaging (MRI) allows highly reliable imaging of the mesorectal fascia (mrMRF) and its relationship to the tumor. The prospective multicenter observational study OCUM uses these findings to indicate neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma. nCRT was indicated in patients with positive mrMRF (≤ 1mm) in cT4 and cT3 carcinomas of the lower rectal third. A total of 527 patients (60.2%) underwent primary total mesorectal excision, and 348 patients (39.8%) underwent long-term nCRT followed by surgery. The mrMRF was involved in 4.6% of the primary surgery group and 80.7% of the nCRT group. Rates of resections within the mesorectal plane (90.8%), sparing of pelvic nerves on both sides (97.8%), and number of regional lymph nodes (95.3% with ≥ 12 lymph nodes examined) are indicative of high-quality surgery. Resection was classified as R0 in 98.3%, the pathological circumferential resection margin (pCRM) was negative in 95.1%.Patients in the nCRT group had more advanced carcinomas with a significantly higher rate of abdominoperineal excision. Independent risk factors for pCRM positivity were advanced stage (T4), metastatic lymph nodes, resection in the muscularis propria plane, and location in the lower third. The risk classification of rectal cancer patients by MRI seems to be highly reliable and allows the restriction of nCRT to approximately half of the patients with clinical stage II and III rectal carcinoma, provided there is a high-quality MRI diagnostic protocol, high-quality surgery, and standardized examination of the resected specimen.

Clinical Outcomes of Patients With Locally Advanced Rectal Cancer With Persistent Circumferential Resection Margin Invasion After Preoperative Chemoradiotherapy.

PurposeTreatment after failure of circumferential resection margin (CRM) conversion after preoperative chemoradiotherapy (pCRT) for locally advanced rectal cancer (LARC) has not been evaluated well. We conducted a single‐center, retrospective analysis to fill this information gap.MethodsFrom 2008 to 2016, we included 112 patients who had predictive CRM involvement on baseline magnetic resonance imaging (MRI) and who underwent surgery following pCRT for LARC. Baseline and posttreatment radiologic and clinical factors were analyzed.ResultsOf 493 patients with LARC, 112 had CRM involvement by baseline MRI (mrCRM). In 40 patients (35.7%), mrCRM involvement was converted as negative posttreatment CRM (ymrCRM−). Multivariate analysis showed the risk factors for persistent CRM involvement (ymrCRM+) after pCRT were extramural venous invasion (mrEMVI+) (P = 0.030) and lower tumor location (P = 0.007). In addition, persistent CRM involvement after pCRT was an independent risk factor for predicting pathologic CRM involvement. The Cox proportional hazard model showed baseline positive mrEMVI remained significant for disease-free survival (DFS) (P < 0.001). On posttreatment MRI, abdominoperineal resection (P = 0.031), intersphincteric resection (P = 0.006), and persistent CRM involvement (P = 0.001) remained significant for local recurrence-free survival. With regard to DFS, persistent CRM involvement (P = 0.048) and positive EMVI on posttreatment MRI (ymrEMVI) (P = 0.014) were significant. In the patient subgroup with persistent CRM involvement, 5-year DFS in patients with mrEMVI and ymrEMVI was 29.8% and 21.2%, respectively.ConclusionPatients who fail to convert to negative CRM have extremely poor oncologic outcomes. Lower tumor height and negative mrEMVI status were good responders to ymrCRM conversion. Our results suggest that these patients require a more intensive treatment modality.

Can CRM Status on MRI Predict Survival in Rectal Cancers: Experience from the Indian Subcontinent

To determine the role of MRI as a predictor of circumferential resection margin (CRM) involvement. To study the impact of CRM status on MRI on recurrence and survival, in correlation with pathology. Analysis of a prospective database was performed over a period of 1year. All patients with adenocarcinoma of rectum were included in the study. The MRI at presentation for all patients irrespective of stage (MRIT), pre-NACTRT MRI (MRI1) for patients with locally advanced tumours, and post-NACTRT MRI (MRI2) of these patients were analysed separately. The status of CRM on MRI was compared to that on histopathology and as a predictor of recurrence and survival. Two hundred twenty-one patients were included with a median follow-up 30months. Sensitivity, specificity, positive predictive value, negative predictive value (NPV) and accuracy were 50%, 65.46%, 5.63%, 96.95% and 64.85% for MRIT; 50%, 55.32%, 5.97%, 95.12% and 55.03% for MRI1; and 77.78%, 63.29%, 10.77%, 98.04% and 64.07% for MRI2, respectively. On multivariate analysis, pathological positive margin alone predicted a poor overall survival (OS) whereas involved CRM on pathology and MRIT predicted poorer disease-free survival (DFS) and local recurrence. Pre-treatment and post-treatment MRI scans have a moderate sensitivity, specificity and accuracy and a high negative predictive value to predict CRM status on pathology. Pathological CRM status is the only factor to impact OS, DFS and LR on multivariate analysis. CRM status on MRI at presentation (MRIT) does impact DFS and local recurrence but not OS.

A rectal cancer feasibility study with an embedded phase III trial design assessing magnetic resonance tumour regression grade (mrTRG) as a novel biomarker to stratify management by good and poor response to chemoradiotherapy (TRIGGER): study protocol for a randomised controlled trial

BackgroundPre-operative chemoradiotherapy (CRT) for MRI-defined, locally advanced rectal cancer is primarily intended to reduce local recurrence rates by downstaging tumours, enabling an improved likelihood of curative resection. However, in a subset of patients complete tumour regression occurs implying that no viable tumour is present within the surgical specimen. This raises the possibility that surgery may have been avoided. It is also recognised that response to CRT is a key determinant of prognosis. Recent radiological advances enable this response to be assessed pre-operatively using the MRI tumour regression grade (mrTRG). Potentially, this allows modification of the baseline MRI-derived treatment strategy. Hence, in a ‘good’ mrTRG responder, with little or no evidence of tumour, surgery may be deferred. Conversely, a ‘poor response’ identifies an adverse prognostic group which may benefit from additional pre-operative therapy.Methods/designTRIGGER is a multicentre, open, interventional, randomised control feasibility study with an embedded phase III design. Patients with MRI-defined, locally advanced rectal adenocarcinoma deemed to require CRT will be eligible for recruitment. During CRT, patients will be randomised (1:2) between conventional management, according to baseline MRI, versus mrTRG-directed management. The primary endpoint of the feasibility phase is to assess the rate of patient recruitment and randomisation. Secondary endpoints include the rate of unit recruitment, acute drug toxicity, reproducibility of mrTRG reporting, surgical morbidity, pathological circumferential resection margin involvement, pathology regression grade, residual tumour cell density and surgical/specimen quality rates. The phase III trial will focus on long-term safety, regrowth rates, oncological survival analysis, quality of life and health economics analysis.DiscussionThe TRIGGER trial aims to determine whether patients with locally advanced rectal cancer can be recruited and subsequently randomised into a control trial that offers MRI-directed patient management according to radiological response to CRT (mrTRG). The feasibility study will inform a phase III trial design investigating stratified treatment of good and poor responders according to 3-year disease-free survival, colostomy-free survival as well as an increase in cases managed without a major resection.Trial registrationClinicalTrials.gov, ID: NCT02704520. Registered on 5 February 2016.

Prospective Validation of a Low Rectal Cancer Magnetic Resonance Imaging Staging System and Development of a Local Recurrence Risk Stratification Model: The MERCURY II Study.

This study aimed to validate a magnetic resonance imaging (MRI) staging classification that preoperatively assessed the relationship between tumor and the low rectal cancer surgical resection plane (mrLRP). Low rectal cancer oncological outcomes remain a global challenge, evidenced by high pathological circumferential resection margin (pCRM) rates and unacceptable variations in permanent colostomies. Between 2008 and 2012, a prospective, observational, multicenter study (MERCURY II) recruited 279 patients with adenocarcinoma 6 cm or less from the anal verge. MRI assessed the following: mrLRP "safe or unsafe," venous invasion (mrEMVI), depth of spread, node status, tumor height, and tumor quadrant. MRI-based treatment recommendations were compared against final management and pCRM outcomes. Overall pCRM involvement was 9.0% [95% confidence interval (CI), 5.9-12.3], significantly lower than previously reported rates of 30%. Patients with no adverse MRI features and a "safe" mrLRP underwent sphincter-preserving surgery without preoperative radiotherapy, resulting in a 1.6% pCRM rate. The pCRM rate increased 5-fold for an "unsafe" compared with "safe" preoperative mrLRP [odds ratio (OR) = 5.5; 95% CI, 2.3-13.3)]. Posttreatment MRI reassessment indicated a "safe" ymrLRP in 33 of 113 (29.2%), none of whom had ypCRM involvement. In contrast, persistent "unsafe" ymrLRP posttherapy resulted in 17.5% ypCRM involvement. Further independent MRI assessed risk factors were EMVI (OR = 3.8; 95% CI, 1.5-9.6), tumors less than 4.0 cm from the anal verge (OR = 3.4; 95% CI, 1.3-8.8), and anterior tumors (OR = 2.8; 95% CI, 1.1-6.8). The study validated MRI low rectal plane assessment, reducing pCRM involvement and avoiding overtreatment through selective preoperative therapy and rationalized use of permanent colostomy. It also highlights the importance of posttreatment restaging.

Circumferential resection margin positivity after preoperative chemoradiotherapy based on magnetic resonance imaging for locally advanced rectal cancer: implication of boost radiotherapy to the involved mesorectal fascia.

To identify patients who are at a higher risk of pathologic circumferential resection margin involvement using preoperative magnetic resonance imaging. Between October 2008 and November 2012, 165 patients with locally advanced rectal cancer (cT4 or cT3 with <2 mm distance from tumour to mesorectal fascia) who received preoperative chemoradiotherapy were analysed. The morphologic patterns on post-chemoradiotherapy magnetic resonance imaging were categorized into five patterns from Pattern A (most-likely negative pathologic circumferential resection margin) to Pattern E (most-likely positive pathologic circumferential resection margin). In addition, the location of mesorectal fascia involvement was classified as lateral, posterior and anterior. The diagnostic accuracy of the morphologic criteria was calculated using receiver operating characteristic curve analysis. Pathologic circumferential resection margin involvement was identified in 17 patients (10.3%). The diagnostic accuracy of predicting pathologic circumferential resection margin involvement was 0.73 using the five-scale magnetic resonance imaging pattern. The sensitivity, specificity, positive predictive value and negative predictive value for predicting pathologic circumferential resection margin involvement were 76.5, 65.5, 20.3 and 96.0%, respectively, when cut-off was set between Patterns C and D. On multivariate logistic regression, the magnetic resonance imaging patterns D and E (P= 0.005) and posterior or lateral mesorectal fascia involvement (P= 0.017) were independently associated with increased probability of pathologic circumferential resection margin involvement. The rate of pathologic circumferential resection margin involvement was 30.0% when the patient had Pattern D or E with posterior or lateral mesorectal fascia involvement. Patients who are at a higher risk of pathologic circumferential resection margin involvement can be identified using preoperative magnetic resonance imaging although the predictability is moderate.