Pathologic Complete Response Rates After Neoadjuvant Treatment in Rectal Cancer: An Analysis of the National Cancer Database

Lorimer, Patrick D.; Motz, B.; Kirks, Russell C.; Boselli, Danielle; Walsh, Kendall; Prabhu, Roshan S.; Hill, Joshua S.; Salo, Jonathan C.

doi:10.1245/s10434-017-5873-8

Cited by 64 publications

(61 citation statements)

References 18 publications

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“…The pCR rate in the 8‐week group was considered to be similar to a 13% pCR rate reported in the literature for a 6–8‐week interval . With the hypothesis that extending the waiting interval to 12 weeks would result in a 2‐fold increase in pCR rate to 26%, the minimum sample size for α = 0.05 and 85% power was 330 patients.…”

Section: Methodsmentioning

confidence: 92%

Randomized controlled trial of 8 weeks’ vs 12 weeks’ interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer

et al. 2019

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Aim The aim was to compare the pathological complete response (pCR) rate at 8 compared to 12 weeks’ interval between completion of neoadjuvant chemoradiotherapy (CRT) and surgery in patients with locally advanced rectal cancer. Method This was a randomized trial which included a total of 330 patients from two institutions. Patients with locally advanced (T3‐4N0M0, TxN+M0) rectal cancer were randomized into 8‐ and 12‐week interval groups. All the patients received long‐course CRT (45 Gy in 1.8 Gy fractions and concomitant oral capecitabine or 5‐fluorouracil infusion). Surgery was performed at either 8 or 12 weeks after CRT. The primary end‐point was pCR. Secondary end‐points were sphincter preservation, postoperative morbidity and mortality. Results Two‐hundred and fifty‐two patients (n = 125 in the 8‐week group, n = 127 in the 12‐week group) were included. Demographic and clinical characteristics were similar between groups. The overall pCR rate was 17.9% (n = 45): 12% (n = 15) in the 8‐week group and 23.6% (n = 30) in the 12‐week group (P = 0.021). Sphincter‐preserving surgery was performed in 107 (85.6%) patients which was significantly higher than the 94 (74%) patients in the 12‐week group (P = 0.016). Postoperative mortality was seen in three (1.2%) patients overall and was not different between groups (1.6% in 8 weeks vs 0.8% in 12 weeks, P = 0.494). Groups were similar in anastomotic leak (10.8% in 8 weeks vs 4.5% in 12 weeks, P = 0.088) and morbidity (30.4% in 8 weeks and 20.1% in 12 weeks, P = 0.083). Conclusion Extending the interval between CRT and surgery from 8 to 12 weeks resulted in a 2‐fold increase in pCR rate without any difference in mortality and morbidity.

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Section: Methodsmentioning

confidence: 92%

Randomized controlled trial of 8 weeks’ vs 12 weeks’ interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer

et al. 2019

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“…Local pathological response to radiochemotherapy impacts on outcome rates after nRCT, irrespective of tumor stage (Mohindra et al 2002 ). However, complete response rates vary between only 5–25%, while around 50% of rectal cancer patients respond poorly or are non-responsive to nRCT (Park et al 2012 ; Ferlay et al 2015 ; Lorimer et al 2017 ). Predictive markers are needed that allow an accurate selection of patients, who will most likely benefit from nRCT or those who could be spared therapy that is associated with high comorbidities.…”

Section: Introductionmentioning

confidence: 99%

FGF8 induces therapy resistance in neoadjuvantly radiated rectal cancer

Harpain

Ahmed

Hudec

et al. 2018

J Cancer Res Clin Oncol

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PurposeTherapy response to neoadjuvant radiochemotherapy (nRCT) of locally advanced rectal cancer varies widely so that markers predicting response are urgently needed. Fibroblast growth factor (FGF) and FGF receptor (FGFR) signaling is involved in pro-survival signaling and thereby may result in radiation resistance.MethodsIn a cohort of 43 rectal cancer patients, who received nRCT, we analyzed protein levels of FGF 8 and its downstream target Survivin by immunohistochemistry to assess their impact on nRCT response. In vitro resistance models were created by exposing colorectal cancer cell lines to fractionated irradiation and selecting long-term survivors.ResultsOur findings revealed significantly higher FGF8 and Survivin staining scores in pre-treatment biopsies as well as in surgical specimens of non-responsive compared to responsive patients. Functional studies demonstrated dose-dependent induction of FGF8 mRNA expression in mismatch-incompetent DLD1 cells already after one dose of irradiation. Surviving clones after one or two series of radiation were more resistant to an additional radiation fraction than non-irradiated controls and showed a significant increase in expression of the FGF8 receptor FGFR3 and of Survivin on both the RNA and the protein levels.ConclusionThe results of this study suggest that FGF8 and Survivin contribute to radiation resistance in rectal cancer and may serve as markers to select patients who may not benefit from neoadjuvant radiotherapy.Electronic supplementary materialThe online version of this article (10.1007/s00432-018-2757-7) contains supplementary material, which is available to authorized users.

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“…In a recent analysis of the National Cancer Database, odds of achieving pCR were independently associated with female sex. Hence, the observed pCR/CR rate of 33% was unlikely skewed due to the over-representation of male patients [25].…”

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confidence: 90%

Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Response in Rectal Cancer: a Pilot Phase I/II Trial

Wong

Chu

Ashamalla

et al. 2020

Preprint

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Background: Neoadjuvant radiotherapy with or without chemotherapy decreases the risk of local recurrence after surgery for stage II or III rectal cancer. Emerging data suggest that diabetic patients on metformin may have improved cancer outcome after radiotherapy. We asked if metformin given concurrently with long course chemoradiation (CRT) may improve pathologic complete response (pCR) in non-diabetic rectal cancer patients. A single-institutional pilot study was performed to build a confidence interval for the pCR rate and to determine the sample size for a phase 2 trial.Methods: Non-diabetic patients with biopsy confirmed adenocarcinoma of the rectum, and deemed candidates for long course neoadjuvant CRT were invited to participate. Radiation consisted of 50.4 Gy in 28 daily fractions. Capecitabine (825 mg/m2 twice daily, Monday-Friday) was self-administered during the 28 days of radiation only. The primary outcome was pCR. The study was designed to accrue 15 participants to construct a confidence interval (CI) for the pCR rate. Results: A total of 16 patients were accrued from January 2017 to May 2018. One patient withdrew from the study prior to CRT. Only grade 1 or 2 adverse events were observed from the intervention. Three patients had a clinical complete response (cCR) and did not have surgical resection. Of the 12 patients who underwent surgery, there were two pCRs. For the combined pCR/cCR rate of 33% (95% CI 19-47%), a total of 85 patients will be required to yield a 95% CI with a 10% margin of error. Conclusions: Adding metformin to neoadjuvant CRT for rectal cancer does not appear to enhance toxicities. These results will be used to refine the design and conduct of a future phase 2 trial to determine whether adding metformin to CRT improves pCR/cCR rates. Trial registration: NCT03053544. Registered December 20, 2016, https://clinicaltrials.gov/ct2/show/record/NCT03053544

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Pathologic Complete Response Rates After Neoadjuvant Treatment in Rectal Cancer: An Analysis of the National Cancer Database

Cited by 64 publications

References 18 publications

Randomized controlled trial of 8 weeks’ vs 12 weeks’ interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer

Randomized controlled trial of 8 weeks’ vs 12 weeks’ interval between neoadjuvant chemoradiotherapy and surgery for locally advanced rectal cancer

FGF8 induces therapy resistance in neoadjuvantly radiated rectal cancer

Metformin With Neoadjuvant Chemoradiation to Improve Pathologic Response in Rectal Cancer: a Pilot Phase I/II Trial

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