scholarly journals Predicting Residual Rectal Adenocarcinoma in the Surgical Specimen after Preoperative Brachytherapy with Endoscopic Ultrasound

2004 ◽  
Vol 18 (7) ◽  
pp. 435-440 ◽  
Author(s):  
Joseph Romagnuolo ◽  
Josée Parent ◽  
Té Vuong ◽  
Mélanie Bélanger ◽  
René P Michel ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Endoscopic Ultrasound ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Resected Specimen ◽  
High Dose ◽  
Residual Tumour ◽  
Predictive Values ◽  
Surgical Specimen ◽  
The Mean

BACKGROUND AND STUDY AIMS:A novel brachytherapy (BT) protocol evaluated at McGill University has shown promise in terms of downstaging and achieving high tumour sterilization rates in rectal cancer. Endoscopic ultrasound (EUS) has emerged as the imaging modality of choice for local staging of rectal cancer. However, external beam radiotherapy appears to decrease the accuracy of EUS from 85% to 40%. The aim of the present study was to prospectively evaluate the accuracy of EUS in assessing the response of rectal cancer to BT.PATIENTS AND METHODS:Thirty-three patients with locally advanced (stage T2 or T3) operable rectal carcinomas were included in an experimental protocol involving a novel conformal technique, using three-dimensional planning, to administer high-dose rate preoperative BT. The 18 patients who were able to have a post-BT EUS exam arranged within two weeks before surgery (eg, four to eight weeks post-BT) were included in this study. Tumour (T)- and lymph node (N)-staging on radial EUS, as well as interpretation of the residual tumour, were assessed prospectively. Pathologists were blinded to the post-BT EUS results.RESULTS:The mean age was 70 years (SD ±11; range, 52 to 93 years) and 78% of the patients were male. Pre-BT EUS indicated that 16 patients (89%) were stage T3, and two were stage T2. Five patients (28%) had positive nodes (N1) by ultrasound. With BT, the mean maximal wall thickness on EUS decreased from 14 mm to 9.4 mm (PÃ0.001). At the time of surgery, seven of the 18 patients (39%) had no detectable tumour in the resected specimen; one had carcinoma in situ, one was stage T1, one was stage T2, and eight were stage T3. Eleven patients (61%) underwent an abdominoperineal resection, including four of the 11 (36%) with no ultimate evidence of residual carcinoma. Eight patients (44%) were node-positive. The sensitivity, specificity, and positive and negative predictive values of post-BT EUS in predicting residual tumour were 82%, 29%, 64% and 50%, respectively. The post-BT EUS accurately predicted the T-stage in eight (44%) patients; most errors were due to overstaging.CONCLUSIONS:Rectal cancer T-staging by EUS post-BT is inaccurate, and although it appears sensitive in predicting the presence or absence of residual tumor in rectal adenocarcinoma after preoperative BT, the low predictive values in this setting limit its utility at this time.

Association of perineural invasion with outcomes after neodjuvant chemoradiation for locally advanced rectal adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 750-750
Author(s):  
Priyanka Vinod Chablani ◽  
Phuong Nguyen ◽  
Charles Andrew Robinson ◽  
Xueliang Jeff Pan ◽  
Steve Andrew Walston ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Perineural Invasion ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Rectal Adenocarcinoma ◽  
Residual Tumor ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Resected Specimen ◽  
Free Survival

750 Background: Perineural invasion (PNI) as a prognostic indicator has not been well studied in patients with rectal adenocarcinoma treated with neoadjuvant chemoradiation (nCRT). In this study, we investigated the incidence and prognostic significance of PNI in patients with stages II-III locally advanced rectal cancer treated with nCRT. Methods: We performed a retrospective study of 110 consecutive patients treated with nCRT for locally advanced rectal adenocarcinoma at a single institution from 2004 to 2011. 88 of these patients had residual tumor in the resected specimen after nCRT. We evaluated the association of PNI with clinical outcomes, including disease-free survival (DFS), distant-metastasis-free survival (DMFS), and overall survival (OS), using log-rank and Cox proportional hazard modeling. Results: Of the 88 patients with residual tumor at surgery, 14 patients (16%) had PNI and 74 patients (84%) did not. Baseline distribution of selected variables in the PNI+ and PNI- groups are shown in Table 1. Median follow-up was 27 months (range 0.9 to 84 months). The median DFS was 13.5 months for PNI+ patients and 39.8 months for PNI- patients (p<0.0001). The median DMFS was 13.5 months for PNI+ patients and median not reached (> 40 months) for PNI- patients (p<0.0001). We did not detect a significant association between the presence of PNI and worse OS, perhaps due to a high rate of censored patients in the OS analysis. In a multivariate model including pT stage, pN stage, tumor location, tumor size, type of surgery, and radial margin status, PNI remained a significant predictor of DFS (HR 16.8, 95% CI, 3.7–75.5, p<0.0002) and DMFS (HR 18.9, 95% CI, 4.4–81.9, p<0.0001). Conclusions: For patients with locally advanced rectal cancer treated with nCRT prior to surgical resection, PNI found at the time of surgery is significantly associated with worse DFS and DMFS. [Table: see text]

Analysis of fiducials implanted during endoscopic ultrasound (EUS) for locally advanced rectal cancer patients receiving high-dose rate endorectal brachytherapy (Endo-HDR).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 655-655
Author(s):  
Shalini Moningi ◽  
Ashkan Malayeri ◽  
Susan Gearhart ◽  
Jonathan Efron ◽  
Elizabeth C. Wick ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Radiation Therapy ◽  
Dose Rate ◽  
Cancer Patients ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
High Dose Rate ◽  
High Dose ◽  
The Mean

655 Background: Rectal cancer affects over 40,000 patients in the US per year. The current standard of care for patients with localized rectal cancer is neoadjuvant radiation therapy with concurrent chemotherapy (NCRT) followed by surgery; however, it has shown no proven survival benefit for locally advanced rectal cancer patients. Preliminary results show that a short course of radiation therapy, using high-dose rate endorectal brachytherapy (Endo-HDR), may be as effective with less toxicity and delay to time of surgery. This requires the placement of fiducial markers, using an endoscopic ultrasound guided method (EUS), into the tumor for accurate source placement and treatment. Our aim is to compare three different types of fiducials in terms of visibility and migration. Methods: 12 patients with locally advanced rectal cancer that received Endo-HDR and EUS guided fiducial placement were retrospectively evaluated at JHH. Results: 12 patients underwent EUS guided placement of 42 fiducials. For 11 of our 12 patients, the mean number of fiducials placed per patient was 3.63 (SD 1.03) using a 19-gauge needle. One patient received 2 fiducials using a 22- gauge needle. Of the 12 patients that received fiducials, 3 received traditional fiducials (TF), 8 received segmented fiducials (SF) and 1 received foldable fiducials. All fiducials were clearly visible. The mean number of fiducials that detached from implanted site before surgery for patients with TFs was 0.667, and for patients with SFs was 0.875 (p=0.744). The median migration distance, as measured by interfiduciary distance, for segmented fiducials was significantly larger when compared to traditional fiducials (0.45 cm for SF compared to 0.1 cm for TF; p=0.049) Conclusions: SFs appear to be less stable, with regards to migration, in the rectum when compared to traditional fiducials in our patient population. These differences could be due to placement difficulty or operator dependent differences. Improvement in fiducial structure is required in order to help decrease migration and detachment and maximize visualization, which will lead to more accurate administration of Endo-HDR.

The effects of neoadjuvant chemoradiation on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal adenocarcinoma.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 101-101
Author(s):  
Moh'd M. Khushman ◽  
Pranitha Prodduturvar ◽  
Shalla Akbar ◽  
Wadad Mneimneh ◽  
Valeria Dal Zotto ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Advanced Rectal Cancer ◽  
Underlying Mechanism ◽  
Staining Intensity ◽  
Normal Mucosa ◽  
Locally Advanced Rectal Cancer ◽  
Concurrent Chemoradiation ◽  
The Mean

101 Background: Exosomes mediate intercellular communications and have pivotal roles in cancer development. CD63 and CD9 are widely accepted exosomal markers. The effect of concurrent chemoradiation on the expression of exosomal markers is unknown. Here we explored the effect of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression in patients with locally advanced rectal cancer (LARC). Methods: Between 2015 and 2018, 33 patients had LARC treated with NCCR and had pre NCCR biopsy and post NCCR resected rectum examined for exosomal markers expression using immunohistochemistry. Two pathologists independently scored CD63 and CD9 staining in the tumor. Staining intensity was graded from 1-3. Staining percentage was estimated in 10% increments. Mean quick-score (Q-score) was calculated (intensity x percentage). Un-Paired t test was used for statistical analysis. Results: In our cohort, median age was 59 years. Males represented 79% of the patients. Caucasians, African American and other ethnic groups represented 70%, 27% and 3% respectively.The mean tumor CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 106 vs 165 (p = 0.0022). The mean tumor CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 136 vs 215 (p < 0.0001). The exosomal markers expression in the adjacent normal mucosa (ANM) from pre NCCR biopsy and post NCCR resected rectum was only performed in16 out of 33 patients (due to ANM tissue availability). The mean ANM CD63 score in pre NCCR biopsy vs post NCCR resected rectum was 166 vs 183 (p = 0.37). The mean ANM CD9 score in pre NCCR biopsy vs post NCCR resected rectum was 104 vs 145 (p = 0.0897). Conclusions: In patients with LARC, the expression of exosomal markers (CD63 and CD9) increased after treatment with NCCR. Our results show that the expression of CD63 and CD9 is relatively higher in rectal cancer specimens treated with NCCR and thus suggest a possible role of these exosomes in adaptive response to NCCR. Further follow-up and laboratory studies are required to precisely understand the underlying mechanism(s).

Role of clinical variables for predicting pathologic response to neoadjuvant chemoradiation in locally advanced rectal cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e14691-e14691
Author(s):  
Paula Mendonca Taglietti ◽  
Samuel Aguiar ◽  
Paulo Henrique Amor Divino ◽  
Maria D. Begnami ◽  
Ranyell Spencer Sobreira Batista ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Residual Disease ◽  
Locally Advanced ◽  
Rectal Adenocarcinoma ◽  
Neoadjuvant Chemoradiation ◽  
Pathologic Response ◽  
Pathological Response ◽  
Resected Specimen ◽  
Clinical Variables ◽  
Endoscopic Assessment

e14691 Background: pathologic response to neoadjuvant chemoradiation is a strong prognostic factor for rectal cancer. Some studies have suggesting a wait and see approach for rectal cancer after clinical complete response to chemoradiation. In this study, we tried to identify clinical predictive factors of pathologic response to neoadjuvant chemoradiation. Methods: we retrospectively reviewed data of 129 patients from a prospective database, treated between January, 2008 and December, 2012. Patients with mid and low rectal adenocarcinoma, clinically staged (MRI) as T3,T4 any N or any T, N+, received pre-operative chemoradiation, which consists in 5040 cGy, concomitant to 5-FU-based chemotherapy. All patients were operated, by radical TME procedures. The clinical variables analyzed were: age, gender, distance from dentate line, cT stage, cN stage, pre-treatment CEA level, NIH toxicity during chemoradiation, endoscopic assessment of response, and interval between the end of radiation and surgery. We investigate associations between these variables with complete pathological response (cPR) and “good” pathological response (gPR), defined as ypT0orT1 N0. Results: the rate of cPR was 20.2%. The rate of gPR was 31.8%. For predicting cPR, only the endoscopic assessment of response showed significant association with cPR. Among 18 patients with complete endoscopic response, 8 (44.4%) confirmed cPR after resection. Among 93 patients with endoscopic findings suggesting residual disease, 14 (15.1%) presented cPR (p=0.008). 55.6% (10/18) of patients with complete endoscopic response still have microscopic residual disease in the resected specimen. For predicting gPR, only the cN staging was significantly associated with ypT0orT1 N0 (23.9% of gPR among cN+ patients against 41.3% among cN0 patients; p=0.038). Conclusions: clinical tools are very poor for predicting pathological response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal carcinomas. Despite endoscopic assessment of response by retoscopy have showed significant association with cPR, the predictive value was weak.

Preoperative high dose rate endorectal brachytherapy (HDREBT) for locally advanced operable rectal cancer

2004 ◽  
Vol 60 ◽  
pp. S294-S294
Author(s):  
T VUONG ◽  
J PARENT ◽  
L PORTELANCE ◽  
G BOURDON ◽  
C EMOND ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Dose Rate ◽  
Locally Advanced ◽  
High Dose Rate ◽  
High Dose

A multicenter phase Ib/II study of DNA-PK inhibitor peposertib (M3814) in combination with capecitabine and radiotherapy in patients with locally advanced rectal cancer.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS144-TPS144
Author(s):  
Paul Bernard Romesser ◽  
Emma B. Holliday ◽  
Tony Philip ◽  
Rocio Garcia-Carbonero ◽  
Jaume Capdevila ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Colon Cancer ◽  
Phase Ii ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Phase Ib

TPS144 Background: Perioperative radiotherapy and chemotherapy, followed by total mesorectal excision, is the standard of care for patients with locally advanced rectal cancer (LARC). However, 1/3 of these patients still develop distant metastases, indicating the need for more effective therapies. In addition, strategies that increase pathological complete response rates are needed to enable non-surgical management of LARC. DNA-dependent protein kinase (DNA-PK) regulates a key DNA damage repair pathway for double-strand break repair. Peposertib (M3814), a potent, selective, orally administered DNA-PK inhibitor, has been shown to potentiate the effect of ionizing radiation in a human colon cancer xenograft model and several colon cancer cell lines. Peposertib is being investigated in several different trials across multiple indications. This Phase Ib/II study (NCT03770689) aims to evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of the neoadjuvant treatment combination of peposertib, capecitabine, and radiotherapy (RT) in patients with LARC. Methods: Patients aged ≥18 years with histologically confirmed and resectable Stage II/III rectal adenocarcinoma are eligible. Induction chemotherapy is permitted, but residual disease must first be documented by MRI, digital rectal examination and endoscopy. Patients who received other anticancer therapies or those with prior pelvic RT are excluded. At open-label Phase Ib (open), 18–30 patients (n = 3 per cohort) will receive peposertib + capecitabine (orally, 825 mg/m2 twice daily [BID]) + RT (45–50.4 Gy), 5 days/week. Peposertib 50 mg once daily (QD) was the starting dose. Additional dose levels will range between 100─800 mg QD. Dose escalation is determined by the safety monitoring committee and guided by a Bayesian 2-parameter logistic regression model. At Phase II (planned), 150 patients will be randomized (1:1) to receive oral capecitabine (825 mg/m2 BID) + RT (45–50 Gy), with either oral peposertib (recommended phase II dose [RP2D] or placebo, QD for 5 days/week. Primary objectives are to define a maximum tolerated dose and RP2D (Phase Ib), and to evaluate the efficacy of peposertib + capecitabine + RT in terms of pathological/clinical complete response (Phase II). Secondary objectives include assessment of antitumor activity (Phase Ib), quality of life outcomes (Phase II), and PK of peposertib, and the safety and tolerability of the combination therapy (both phases). To date, one patient has received peposertib 50 mg QD, six patients peposertib 100 mg QD, three patients peposertib 150 mg QD, and three patients peposertib 250 mg QD. Clinical trial information: NCT03770689.

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