Pathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) of uT2uN0 rectal cancer (RC) treated by local excision (LE): Results of the ACOSOG Z6041 trial.

e14535 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August, 2005 to July, 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19% N1 or N2, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]

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Assessment of macroscopic features in relation to tumor response to neoadjuvant chemoradiation therapy in rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.507 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 507-507

Author(s):

Amanda Kathleen Arrington ◽

Julio Garcia-Aguilar ◽

Marjun Philip Duldulao ◽

Carrie Luu ◽

Julian Sanchez ◽

...

Keyword(s):

Rectal Cancer ◽

Tumor Response ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Chemoradiation Therapy ◽

Oncologic Outcomes ◽

Neoadjuvant Chemoradiation Therapy ◽

Pathologic Features

507 Background: Several studies show locally advanced rectal cancer patients with clinical complete response (cCR) have comparable oncologic outcomes to pathologic complete response (pCR) to neoadjuvant chemoradiation therapy (NCRT). Thus, total mesorectal excision (TME) could potentially be avoided. Our objective was to validate macroscopic features of cCR. Methods: 164 patients with stage II/III rectal cancer were previously enrolled in a phase II trial and treated by NCRT and TME. Tumor response in the surgical specimens was assessed according to AJCC guidelines. A pCR was defined as absence of viable tumor cells. Gross macroscopic features by the pathologist were tabulated and our cohort was applied to previously published cCR criteria. Results: 25.0% (n = 41) had pCR; 75.0% (n = 123) had non-pCR. Descriptors were condensed into 14 macroscopic features by combining terms and excluding those rarely mentioned. Several reports affirm that scarring signifies cCR, while others suggest that fibrosis, edema, ulceration and nonpalpable tumor to be consistent with cCR. In our study, scarring was found in 6.1% of patients, 16.7% of which had pCR. We found that hyperemia, scarring, flat, smooth, and tan-pink mucosa were significantly associated with pCR (p < 0.05). In contrast, a firm lesion and ulceration were frequently observed in patients with non-pCR (p = 0.02 and 0.05 respectively). Conclusions: Our study suggests that macroscopic pathologic features do correlate with pCR. Although cCR has comparable oncologic outcomes as pCR with favorable outcomes, standard criteria of cCR should first be defined so NCRT patients can safely be selected for observation only. [Table: see text]

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Survival differences in patients (pts) with resected rectal cancer who received neoadjuvant therapy with or without postoperative chemotherapy (CT).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.518 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 518-518

Author(s):

Christina Sing-Ying Wu ◽

Lai Wei ◽

Katherine Glass ◽

John Wilson ◽

Sherif Abdel-Misih ◽

...

Keyword(s):

Rectal Cancer ◽

Survival Benefit ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Wilcoxon Test ◽

Stage Ii ◽

Categorical Variables ◽

Rank Test ◽

Significant Difference

518 Background: Pts with stage II/III rectal cancers are treated with neoadjuvant chemoradiation and surgical resection followed by adjuvant CT per practice guidelines. It is unclear whether adjuvant CT provides survival benefit, and the purpose of this study was to measure outcome in pts who did and did not receive adjuvant CT. Methods: We used a prospectively collected database for pts treated at The Ohio State University, and analyzed overall survival (OS), time to recurrence (TTR), pt characteristics, tumor features, and treatments. Survival curves were estimated using Kaplan-Meier method and compared by the log-rank test. Age was compared using the Wilcoxon test, and other categorical variables were compared using Chi-square test or Fisher’s exact test. Results: Between August 2005 to July 2011, 110 pts were identified and 71 pts had received adjuvant CT. There was no significant difference in sex, race, pathologic tumor (T) stage, and pathologic complete response between the two pt groups. Pts receiving adjuvant CT were significantly younger (median age 54.3 vs. 62 years, p=0.01) and had more advanced pathologic nodal (N) stage (43 vs. 19%, p=0.02). Median OS was 72.6 months with CT vs. 36.4 months without CT (p=0.0003). Median TTR has not yet been reached. Conclusions: In this retrospective analysis, adjuvant CT was associated with a longer OS despite more advanced pathologic nodal staging. Prospective randomized studies are warranted to determine whether adjuvant CT provides a survival benefit for pts across the spectrum of stage II and III rectal cancer. [Table: see text]

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Residual rectal cancer after preoperative radiochemotherapy (ypT1-2): An indication for local excision instead of radical surgery?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.546 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 546-546

Author(s):

Thilo Sprenger ◽

Hilka Rothe ◽

Lena-Christin Conradi ◽

Kia Homayounfar ◽

Tim Beissbarth ◽

...

Keyword(s):

Rectal Cancer ◽

Local Excision ◽

Bowel Wall ◽

Radical Surgery ◽

Pathologic Complete Response ◽

Residual Tumor ◽

Complete Response ◽

Phase Iii ◽

Preoperative Radiochemotherapy ◽

Cancer Trial

546 Background: Preoperative radiochemotherapy (RCT) followed by total mesorectal excision (TME) has improved local tumor control and led to a significant tumor downstaging. For patients with pathologic complete response (ypT0) as well as residual tumor restricted only to the bowel wall (ypT1-2) local excision has increasingly been discussed to avoid significant morbidity and functional deficits associated with TME. Therefore we investigated the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with ypT0, ypT1-2 and ypT3-4 rectal cancers, respectively. Methods: TME specimens from 81 patients with locally advanced rectal cancer treated with neoadjuvant RCT within the phase III German Rectal Cancer Trial CAO/ARO/AIO-04 were evaluated. The entire mesorectal compartment was screened microscopically after complete paraffin embedding. The number and localization of all detectable LN metastases was specified in relation to the primary tumor. Results: Whereas 50 patients (62%) had ypT3-4 carcinomas after neoadjuvant RCT 20 patients (25%) presented with residual tumor within the bowel wall (ypT1-2). 11 patients (14%) had pathologic complete response (ypT0). 28 ± 13.7 LN were detected per specimen. 25 patients (31%) had residual LN metastases after RCT. Although the incidence was higher in the ypT3-4 group (40% ypN+) still 25% of patients in the ypT1-2 group had a mean number of 2.2 residual LN metastases. 55% of these metastases were located afar from the primary lesion in the proximal mesorectum. No patient with ypT0 status had residual LN metastases. Conclusions: Even in patients with good response and tumors restricted only to the bowel wall (ypT1-2) after RCT there is a considerable risk for residual LN metastases. The majority of metastases were located clearly outside the tumor region. Local excision of residual rectal cancer would be accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in those patients.

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Totally neoadjuvant chemoradiation therapy with mFOLFOX6 in locally advanced rectal cancer: A single arm phase II study (FOTAC).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.tps816 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. TPS816-TPS816

Author(s):

Jianwei Zhang ◽

Yue Cai ◽

Huabin Hu ◽

Jian Xiao ◽

Dianke Chen ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii Study ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Neoadjuvant Chemoradiation ◽

Chemoradiation Therapy ◽

Neoadjuvant Chemoradiation Therapy

TPS816 Background: Preoperative 5-Fluorouracil based chemoradiotherapy is the standard of treatment for locally advanced rectal cancer. About 15% to 18% of patients would achieve pathologic complete response (pCR) after 5-Fluorouracil based chemoradiation. And the survival outcome of patients with pCR was much better than that of non-pCR. In our previous FOWARC study, in the group of preoperative systemic chemotherapy with mFOLFOX6 combined with radiation, the pCR rate was up to 27.5%. In another study, adding mFOLFOX6 after neoadjuvant chemo radiation in locally advanced rectal cancer improve the pCR rate to 38%. This phase II study aimed to explore whether totally neoadjuvant chemoradiation therapy with mFOLFOX6 could further improve the pCR rate in locally advanced rectal cancer. Methods: The primary endpoint is the pathologic complete response rate (pCR).The secondary endpoint included 3-year disease free survival rate, 3-year local recurrence rate, and safety. We hypothesized that totally neoadjuvant chemoradiation therapy with mFOLFOX6 could improve the pCR rate from 18% to 45% with 5% type I error and 80% power. Fifty patients met inclusion criteria will be enrolled in the trial. All patients will receive long term radiation for 25 times and 50Gy before surgery. Four cycles of mFOLFOX6 would be performed every 2 weeks during radiotherapy, and another 4-6 cycles would be added after radiotherapy and before operation. Totally, the patients will receive 8-10 cycles of chemotherapy before surgery. MRI of the pelvic will be performed every 4 cycles of the therapy to assess clinical response. Then the patient will receive total mesorectal excision at least 8 weeks after radiotherapy. The post-operative chemotherapy will be omitted and all the patients go to surveillance. Clinical trial information: NCT02887313.

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Association of adjuvant chemotherapy with improved overall survival for patients with locally advanced rectal cancer (LARC) who achieve a pathologic complete response (pCR) to neoadjuvant chemoradiation (nCRT).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.716 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 716-716

Author(s):

Danish Shahab ◽

Emmanuel M. Gabriel ◽

Kristopher Attwood ◽

Valerie Francescutti ◽

Wen Wee Ma ◽

...

Keyword(s):

Rectal Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Adjuvant Therapy ◽

Locally Advanced ◽

Pathologic Complete Response ◽

Complete Response ◽

Neoadjuvant Chemoradiation ◽

Comorbidity Score ◽

N Stage

716 Background: 15-20% of patients with locally advanced rectal adenocarcinoma (LARC) achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation (nCRT). The role of adjuvant chemotherapy has been questioned. Methods: Patients with rectal cancer receiving nCRT in the National Cancer Data Base (NCDB) 2006-2013 data set were evaluated. The primary outcome was overall survival (OS). The association between OS and patient characteristics were examined using multivariable Cox regression models. Results: 2,903 patients were identified who achieved a pCR. The median follow up was 43.2 months. 2,102 received nCRT and 789 received nCRT + adjuvant chemotherapy. Factors significantly associated with OS included age (p<0.001), gender (p=0.011), Charlson-Deyo comorbidity score (CDI) (p<0.001), grade (p=0.029), clinical T stage (p=0.030), and CEA negativity (p=0.002), but not nodal status. The 3-year OS rate was 94% in the adjuvant therapy group as compared to 84% in the nCRT alone group (p<0.001). In considering clinical N-stage, the benefit was comparable for both N+ and N- tumors. Adjuvant chemotherapy was more likely to be given for younger patients (age < 60), lower comorbidity score, higher grade, positive CEA status, higher clinical T stage, and higher clinical N stage. When stratifying by these factors, similar benefits in OS were observed in the adjuvant cohort. Conclusions: Following nCRT and achievement of a pCR, the receipt of adjuvant chemotherapy is associated with improved OS. Patients receiving adjuvant therapy were more likely to be younger and have a low CDI, but have more advanced stage disease. Thus, a selection bias may be present. Nonetheless, in the setting of the already excellent outcome associated with pCR, the additional benefit of adjuvant chemotherapy should be weighed against toxicity.

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