The Impact of Total Neo-adjuvant Treatment on Nonoperative Management in Patients With Locally Advanced Rectal Cancer: The Evaluation of 66 Cases in a Single Center

In locally advanced rectal cancer, radiotherapy (RT) followed by surgery have improved locoregional control, but distant recurrences remain frequent. Although checkpoint inhibitors have demonstrated objective response in several cancers, the clinical benefit of PD-1/PD-L1 blockade remains uncertain in rectal cancer. We collected data from biopsies and surgical specimens in 74 patients. The main objective was to evaluate the impact of neoadjuvant RT and fractionation on PD-L1 expression. Secondary objectives were to study the relation between PD-L1 expression and tumor regression grade (TRG), progression-free survival (PFS), overall survival (OS), and CD8 TILs infiltration. Median rates of cells expressing PD-L1 pre- and post-RT were 0.15 (range, 0–17) and 0.5 (range, 0–27.5), respectively (p = 0.0005). There was no effect of RT fractionation on PD-L1+ cell rates. We found no relation between CD8+ TILs infiltration and PD-L1 expression and no difference between high-PD-L1 or low-PD-L1 expression and TRG. High-to-high PD-L1 expression profile had none significant higher OS and PFS compared to all other groups (p = 0.06). Median OS and PFS were higher in biopsies with >0.08 PD-L1+ cells. High-to-high PD-L1 profile and ypT0-2 were significantly associated with higher OS and PFS. This study did not show the differential induction of PD-L1 expression according to fractionation.

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Primary Tumor Response to Preoperative Chemoradiation With or Without Oxaliplatin in Locally Advanced Rectal Cancer: Pathologic Results of the STAR-01 Randomized Phase III Trial

Journal of Clinical Oncology ◽

10.1200/jco.2010.34.4911 ◽

2011 ◽

Vol 29 (20) ◽

pp. 2773-2780 ◽

Cited By ~ 496

Author(s):

Carlo Aschele ◽

Luca Cionini ◽

Sara Lonardi ◽

Carmine Pinto ◽

Stefano Cordio ◽

...

Keyword(s):

Rectal Cancer ◽

Primary Tumor ◽

Tumor Response ◽

Locally Advanced ◽

Muscularis Propria ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Phase Iii ◽

Preoperative Treatment ◽

The Impact

Purpose To investigate oxaliplatin combined with fluorouracil-based chemoradiotherapy as preoperative treatment for locally advanced rectal cancer. Patients and Methods Seven hundred forty-seven patients with resectable, locally advanced (cT3-4 and/or cN1-2) adenocarcinoma of the mid-low rectum were randomly assigned to receive pelvic radiation (50.4 Gy in 28 daily fractions) and concomitant infused fluorouracil (225 mg/m2/d) either alone (arm A, n = 379) or combined with oxaliplatin (60 mg/m2 weekly × 6; arm B, n = 368). Overall survival is the primary end point. A protocol-planned analysis of response to preoperative treatment is reported here. Results Grade 3 to 4 adverse events during preoperative treatment were more frequent with oxaliplatin plus fluorouracil and radiation than with radiation and fluorouracil alone (24% v 8% of treated patients; P < .001). In arm B, 83% of the patients treated with oxaliplatin had five or more weekly administrations. Ninety-one percent, compared with 97% in the control arm, received ≥ 45 Gy (P < .001). Ninety-six percent versus 95% of patients underwent surgery with similar rates of abdominoperineal resections (20% v 18%, arm A v arm B). The rate of pathologic complete responses was 16% in both arms (odds ratio = 0.98; 95% CI, 0.66 to 1.44; P = .904). Twenty-six percent versus 29% of patients had pathologically positive lymph nodes (arm A v arm B; P = .447), 46% versus 44% had tumor infiltration beyond the muscularis propria (P = .701), and 7% versus 4% had positive circumferential resection margins (P = .239). Intra-abdominal metastases were found at surgery in 2.9% versus 0.5% of patients (arm A v arm B; P = .014). Conclusion Adding oxaliplatin to fluorouracil-based preoperative chemoradiotherapy significantly increases toxicity without affecting primary tumor response. Longer follow-up is needed to assess the impact on efficacy end points.

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The impact of driving time, distance, and socioeconomic factors on outcomes of patients with locally advanced rectal cancer

Public Health in Practice ◽

10.1016/j.puhip.2020.100012 ◽

2020 ◽

Vol 1 ◽

pp. 100012

Author(s):

Joanna Gotfrit ◽

Tharshika Thangarasa ◽

Shaan Dudani ◽

Rachel Goodwin ◽

Patricia A. Tang ◽

...

Keyword(s):

Rectal Cancer ◽

Socioeconomic Factors ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Driving Time ◽

Time Distance ◽

The Impact

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

BMC Cancer ◽

10.1186/1471-2407-13-576 ◽

2013 ◽

Vol 13 (1) ◽

Cited By ~ 10

Author(s):

Joo Ho Lee ◽

Eui Kyu Chie ◽

Kyubo Kim ◽

Seung-Yong Jeong ◽

Kyu Joo Park ◽

...

Keyword(s):

Rectal Cancer ◽

Treatment Response ◽

Resection Margin ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer ◽

Margin Status ◽

Resection Margin Status ◽

The Impact

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A randomized phase II study of capecitabine-based chemoradiation with or without bevacizumab in resectable locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.3571 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 3571-3571 ◽

Cited By ~ 1

Author(s):

Mercedes Martinez Villacampa ◽

Jaume Capdevila ◽

Jose Luis Manzano ◽

Carles Pericay ◽

Ramon Salazar ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Correct Selection ◽

Randomized Phase Ii ◽

Grade 3 ◽

The Impact

3571 Background: The addition of bevacizumab (BEV) to capecitabine (CAP)-based chemoradiation (CRT) has shown encouraging efficacy in locally advanced rectal cancer (LARC), in nonrandomized studies. This randomized phase II study investigated the effect of adding BEV to preoperative CAP-based CRT in patients (pts), with LARC. Methods: The primary end point was pathologic complete response (pCR). A two-stage design was used. Assuming a minimum pCR rate of at least 15% in one of the arms, a difference between the two arms of 10%, and accepting a probability of correct selection of 87%, 41 pts per arm were needed. Patients with LARC (Stages II-III assessed by MRI) and ECOG PS <2 were randomized to concurrent radiotherapy 45Gy/25f/5 weeks + CAP (825mg/m²/bid) + BEV every 2 weeks (5 mg/kg for 3 doses) (arm A) or the same schedule without BEV (arm B). Surgery was scheduled 6-8 weeks after completing CRT. Results: 90 pts were randomized (arm A/B: 44/46). Patient’s characteristics were well balanced between both arms: male 61%, median age 62 years, median distance from anal verge 7 cm, T3 79%, N+ 87%. 40 (91%)/43 (93%) of pts (arm A/B) finalized the planned CRT + surgery treatment. Overall grade 3-4 toxicity rates were 18 % and 13% (arm A/B, p=0.50); no grade 3-4 hematological toxicity was reported. Postoperative complications were 19(43%)/17(37%)(arm A/B). Efficacy data on patients who actually underwent surgery are reported in the table. Conclusions: The addition of BEV to CAP-based preoperative CRT has shown to be feasible and safe in the local control of LARC. No differences in pCR were observed and longer follow-up is needed to assess the impact on survival endpoints. [Table: see text]

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Effects of adjuvant oxaliplatin on anal function in locally advanced rectal cancer treated with preoperative chemoradiotherapy and low anterior resection.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.718 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. 718-718

Author(s):

Fernando Arias ◽

Clara Eito ◽

Antonio Viudez ◽

Gemma Asin ◽

Berta Ibañez ◽

...

Keyword(s):

Rectal Cancer ◽

Adjuvant Treatment ◽

Anterior Resection ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Anal Function ◽

Sphincter Function ◽

Anal Sphincter Function ◽

Incontinence Score

718 Background: The main purpose of the present study was to determine if the addition of adjuvant oxaliplatin (OXA) could have some influence on sphincter function in patients with locally advanced rectal cancer (LARC) treated with preoperative capecitabine/radiotherapy followed by lower anterior resection (LAR). Methods: Those patients with LARC treated at our center with LAR and without two-years loco-regional relapse were retrospectively analyzed independent of the type of adjuvant treatment received. Anal sphincter function was assessed by Wexner´s incontinence score (0 to 20 points, being punctuation inversely proportional to sphincter function). All questionnaires were completed between January 2010 and December 2012. Comparisons of sphincter function measured with the Wexner test between patients with and without OX were conducted with the Mann-Whitney test. Statistical analyses were conducted using IBM SPSS Statistics, version 20. Results: From 2006, 92 consecutive patients were included in our study. Mean time from LAR to fecal function assessment was 58 months (25 to 96 months). Wexner test median values did not differ significantly (p=0.450) between patients with and without adjuvant OXA. The median (IQR) for the group without adjuvant OXA was 6.0 (1.0-11.25), being for group that received adjuvant OXA of 5.0 (1.0-10.0). Conclusions: Based on our findings, OXA could be used as adjuvant treatment in LARC, due to its absent of deleterious influence over the sphincter anal function. Because of the retrospective nature of our study, prospective studies should be warranted in similar scenarios. This study has been supported by a grant of “Mutua Madrileña Fundation.”

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