Dataset Information

Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort.

ABSTRACT:

Background

In rectal cancer, prediction of tumor response and pathological complete response (pCR) to neoadjuvant treatment could contribute to refine selection of patients who might benefit from a delayed- or no-surgery approach. The aim of this study was to explore the association of clinical and molecular characteristics of rectal cancer with response to neoadjuvant treatment and to compare patient survival according to level of response.

Methods

Resected rectal cancer patients were selected from a population-based cohort study. Molecular tumor markers were determined from the surgical specimen. Tumor response and pCR were defined as downstaging in T or N stage and absence of tumor cells upon pathological examination, respectively. The associations of patient and tumor characteristics with tumor response and pCR were explored, and patient survival was determined by degree of response to neoadjuvant treatment.

Results

Among 1536 patients with rectal cancer, 602 (39%) received neoadjuvant treatment. Fifty-five (9%) patients presented pCR, and 239 (49%) and 250 (53%) patients showed downstaging of the T and N stages, respectively. No statistically significant associations were observed between patient or tumor characteristics and tumor response or pCR. Patients who presented any type of response to neoadjuvant treatment had significantly better cancer-specific and overall survival compared with non-responders.

Conclusion

In this study, patient characteristics were not associated with response to neoadjuvant treatment, and molecular characteristics determined after surgical resection of the tumor were not predictive of pCR or tumor downstaging. Future studies should include molecular biomarkers from biopsy samples before neoadjuvant treatment.

SUBMITTER: Alwers E

PROVIDER: S-EPMC7782441 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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Publications

Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort.

Alwers Elizabeth E Jansen Lina L Kather Jakob J Amitay Efrat E Bläker Hendrik H Kloor Matthias M Tagscherer Katrin E KE Roth Wilfried W Herpel Esther E Chang-Claude Jenny J Brenner Hermann H Hoffmeister Michael M

International journal of colorectal disease 20200919 1

<h4>Background</h4>In rectal cancer, prediction of tumor response and pathological complete response (pCR) to neoadjuvant treatment could contribute to refine selection of patients who might benefit from a delayed- or no-surgery approach. The aim of this study was to explore the association of clinical and molecular characteristics of rectal cancer with response to neoadjuvant treatment and to compare patient survival according to level of response.<h4>Methods</h4>Resected rectal cancer patients ...[more]

PMID: 32949260

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Project description:Background: Patients with rectal cancer who achieve pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) may have a better prognosis and may be eligible for non-operative management. The aim of this research was to identify variables for predicting pCR in rectal cancer patients after nCRT and to define clinical risk factors for poor outcome after pCR to nCRT and radical resection in rectal cancer patients. Methods: A retrospective review was performed using the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2013. Non-metastatic rectal cancer patients who received radical resection after neoadjuvant chemoradiotherapy were included in this study. Multivariate analysis of the association between clinicopathological characteristics and pCR was performed, and a logistic regression model was used to identify independent predictors for pCR. A nomogram based on the multivariate logistics regression was built with decision curve analyses to evaluate the clinical usefulness. Results: A total of 6,555 patients were included in this study. The proportion of patients with pCR was 20.5% (n = 1,342). The nomogram based on multivariate logistic regression analysis showed that clinical T4 and N2 stages were the most significant independent clinical predictors for not achieving pCR, followed by mucinous adenocarcinoma and positive pre-treatment serum CEA results. The 3-year overall survival rate was 92.4% for those with pCR and 88.2% for those without pCR. Among all the pCR patients, mucinous adenocarcinoma patients had the worst survival, with a 3-year overall survival rate of 67.5%, whereas patients with common adenocarcinoma had an overall survival rate of 93.8% (P < 0.001). Univariate and multivariate analyses showed that histology and clinical N2 stage were independent risk factors. Conclusion: Mucinous adenocarcinoma, positive pre-treatment serum CEA results, and clinical T4 and N2 stages may impart difficulty for patients to achieve pCR. Mucinous adenocarcinoma and clinical N2 stage might be indicative of a prognostically unfavorable biological tumor profile with a greater propensity for local or distant recurrence and decreased survival.

Project description:BACKGROUND:In recent decades, neoadjuvant therapy (NT) has been the standardized treatment for locally advanced rectal cancer (LARC). Approximately 8%-35% of patients with LARC who received NT were reported to have achieved a complete pathological response (pCR). If the pathological response (PR) can be accurately predicted, these patients may not need surgery. In addition, no response after NT implies that the tumor is destructive, resistant to both chemotherapy and radiotherapy, and prone to having a high metastatic potential. Therefore, developing accurate models to predict PR has great clinical significance and can help achieve individualized treatment in LARC patients. AIM:To establish nomograms for predicting PR to different NT regimens based on pretreatment parameters for patients with LARC. METHODS:Rectal cancer patients were identified from the database of The Sixth Affiliated Hospital, Sun Yat-sen University from January 2012 to December 2016. Logistic regression and nomograms were developed to predict the probability of pCR and good downstaging to ypT0-2N0M0 (ypTNM 0-I), respectively, based on pretreatment parameters for all LARC patients. Nomograms were also developed for three NT regimens (capecitabine/deGramont-RT, mFOLFOX6, and mFOLFOX6-RT) to predict pCR probability. RESULTS:Four hundred and three patients were included in this study; 72 (17.9%) had pCR at the final pathology report, and 177 (43.9%) achieved good downstaging to ypT0-2N0M0 (ypTNM 0-I). The nomogram for predicting pCR probability showed that NT regimens, tumor differentiation, mesorectal fascia (MRF) status, and tumor length significantly influenced pCR probability. When predicting the probability of good downstaging, tumor differentiation, MRF status, and clinical T stage were the significant factors. Nomograms were developed based on NT regimens. For the capecitabine/de Gramont-RT group, the multivariate analysis showed that the neutrophil-lymphocyte ratio (NLR) was the only significant factor, thus we could not develop a nomogram for this regimen. For the mFOLFOX6-RT group, the analysis showed that the significant factors were tumor length and MRF status; and for the mFOLFOX6 group, the significant factors were tumor length and tumor differentiation. CONCLUSION:We established accurate nomograms for predicting the PR to preoperative NT regimens based on pretreatment parameters for LARC patients.

Project description:BACKGROUND:Neoadjuvant radiotherapy (RT) has been shown to improve local control; however, whether it can improve overall survival (OS) in locally advanced rectal cancer (LARC) patients remains controversial. We therefore aimed to examine the benefits of surgery alone, neoadjuvant radiotherapy (RT), adjuvant RT, and surgery plus chemotherapy in stage II (T3/4N0M0) and III (any T and N?+?M0) on the OS of rectal cancer patients. METHODS:Date from the Surveillance, Epidemiology, and End Results (SEER) database diagnosed between 2004 and 2016 were used. Kaplan-Meier analyses were used to compare patient prognoses across different treatment modalities. Cox hazard regression analysis were used to identify independent predictors of OS. RESULTS:For stage T3/4N0M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p?>?0.05; mean survival, 115.89?months (M), 111.97?M, and 117.22?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p?<?0.001, mean survival, 88.96?M). For stage T1/2N?+?M0 patients, neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy resulted in similar OS (all p?>?0.05; mean survival, 121.50?M, 124.25?M, and 121.20?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p?<?0.001, mean survival 83.81?M). For stage T3/4N?+?M0 patients, neoadjuvant RT (HR?=?0.436; 95% CI, 0.396~0.478; p?<?0.001) resulted in significantly longer OS than adjuvant RT and surgery plus chemotherapy (mean survival, 104.47?M, 93.94?M, and 93.62?M, respectively), with better OS observed in these patients than in patients who underwent surgery alone (all p?<?0.001, mean survival 54.87?M). Older age (>?60?years), black race, unmarried status, high tumour grade, and tumour size >?5?cm were all associated with a poor prognosis (all p?<?0.05). CONCLUSIONS:Neoadjuvant RT, adjuvant RT, and surgery plus chemotherapy results in better OS than surgery alone in LARC patients. Neoadjuvant RT has the potential to be highly recommended over adjuvant RT and surgery plus chemotherapy for T3/4N?+?M0 patients; however, it showed no OS advantage over adjuvant RT or surgery plus chemotherapy for T3/4N0M0 and T1/2N?+?M0 patients.

Project description:Purpose To investigate the value of T2-weighted-based radiomics compared with qualitative assessment at T2-weighted imaging and diffusion-weighted (DW) imaging for diagnosis of clinical complete response in patients with rectal cancer after neoadjuvant chemotherapy-radiation therapy (CRT). Materials and Methods This retrospective study included 114 patients with rectal cancer who underwent magnetic resonance (MR) imaging after CRT between March 2012 and February 2016. Median age among women (47 of 114, 41%) was 55.9 years (interquartile range, 45.4-66.7 years) and median age among men (67 of 114, 59%) was 55 years (interquartile range, 48-67 years). Surgical histopathologic analysis was the reference standard for pathologic complete response (pCR). For qualitative assessment, two radiologists reached a consensus. For radiomics, one radiologist segmented the volume of interest on high-spatial-resolution T2-weighted images. A random forest classifier was trained to separate the patients by their outcomes after balancing the number of patients in each response category by using the synthetic minority oversampling technique. Statistical analysis was performed by using the Wilcoxon rank-sum test, McNemar test, and Benjamini-Hochberg method. Results Twenty-one of 114 patients (18%) achieved pCR. The radiomic classifier demonstrated an area under the curve of 0.93 (95% confidence interval [CI]: 0.87, 0.96), sensitivity of 100% (95% CI: 0.84, 1), specificity of 91% (95% CI: 0.84, 0.96), positive predictive value of 72% (95% CI: 0.53, 0.87), and negative predictive value of 100% (95% CI: 0.96, 1). The diagnostic performance of radiomics was significantly higher than was qualitative assessment at T2-weighted imaging or DW imaging alone (P < .02). The specificity and positive predictive values were significantly higher in radiomics than were at combined T2-weighted and DW imaging (P < .0001). Conclusion T2-weighted-based radiomics showed better classification performance compared with qualitative assessment at T2-weighted and DW imaging for diagnosing pCR in patients with locally advanced rectal cancer after CRT. © RSNA, 2018 Online supplemental material is available for this article.

Dataset Information

Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort.

Background

Methods

Results

Conclusion

Publications

Response to neoadjuvant treatment among rectal cancer patients in a population-based cohort.

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