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Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma: a single center experience.

ABSTRACT: OBJECTIVE:: To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT). METHODS:: This study recruited 64 patients. The patients had resectable cancer of the lower and the middle rectum (T3/T4 and/or N+) without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal excision (TME) between January 2006 and December 2011. The patients were classified into non-response (NR), partial response (PR), and pathologic complete response (pCR) based on the Dworak tumor regression grading system. RESULTS:: The median age of patients was 57 years (ranging from 22 to 85). A total of 24 patients were treated with neoadjuvant CCRT, whereas 40 patients were treated with RT alone. Abdominoperineal resection (APR) was performed on 29 patients (45%). Anterior resection with TME was performed on 34 patients (53%). One patient had local resection. Histologically, 12 (19%), 24 (73%), and 28 (44%) patients exhibited pCR, PR, and NR, respectively. Univariate analysis revealed that the predictors of tumor regression were as follows: the absence of lymph node involvement from initial imaging (cN0) (P=0.021); normal initial carcinoembryonic antigen (CEA) level (P=0.01); hemoglobin level ?12 g/dl (P=0.009); CCRT (P=0.021); and tumor downstaging in imaging (P=0.001). Multivariate analysis showed that the main predictors of pCR were CT combined with neoadjuvant RT, cN0 stage, and tumor regression on imaging. CONCLUSIONS:: Identifying the predictors of pCR following neoadjuvant therapy aids the selection of responsive patients for non-aggressive surgical treatment and possible surveillance.

SUBMITTER: Letaief F

PROVIDER: S-EPMC5570609 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma: a single center experience.

Letaief Feryel F Nasri Meher M Ayadi Mouna M Meddeb Khedija K Mokrani Amina A Yahyaoui Yosra Y Chraiet Nesrine N Raies Henda H Mezlini Amel A

Cancer biology & medicine 20170801 3

<h4>Objective</h4>: To assess the response rate of patients with rectal adenocarcinoma to neoadjuvant therapy and to identify the predictors of histological regression after neoadjuvant radiotherapy (RT) or concurrent chemoradiotherapy (CCRT).<h4>Methods</h4>: This study recruited 64 patients. The patients had resectable cancer of the lower and the middle rectum (T3/T4 and/or N+) without distant metastasis and received neoadjuvant RT or CCRT followed by radical surgery with total mesorectal exci ...[more]

PMID: 28884049

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Project description:ObjectivePathologic complete response (pCR) of breast cancer after neoadjuvant chemotherapy (NAC) is highly related to molecular subtypes. Patients who achieved tumor pCR after NAC have a better prognosis. However, despite of better prognosis, pCR patients have a potential for recurrence. There is little evidence of risk factors of recurrence in patients with pCR. We aim to analyze factors associated with tumor recurrence in patients who achieved pCR.MethodsThis study retrospectively reviewed the data of patients diagnosed with breast cancer who achieved pCR after receiving NAC between January 2009 and December 2018 in Samsung Medical Center. pCR was defined as no residual invasive cancer in the breast and axillary nodes even if there is residual ductal carcinoma in situ (ypT0 or ypTis with ypN0). Breast cancers are classified into 4 subtypes based on hormone receptors (HR) and human epithelial growth factor receptor 2 (HER2) status. Patients who had bilateral breast cancer, ipsilateral supraclavicular or internal mammary lymph node metastasis, inflammatory breast cancer, distant metastasis, unknown subtype, and histologically unique case were excluded from the study.ResultsIn total 483 patients were included in this study except for patients who corresponded to the exclusion criteria. The median follow-up duration was 59.0 months (range, 0.5-153.3 months). Breast cancer recurred in 4.1% of patients (20 of 483). There was a significant difference in clinical T (P = 0.004) and clinical N (P = 0.034) stage in the Kaplan-Meier curve for disease-free survival. Molecular subtypes (P = 0.573), Ki67 (P = 1.000), and breast surgery type (P = 0.574) were not associated with tumor recurrence in patients who achieved pCR after NAC. In the clinical T stage and clinical N stage, there was a significant difference between recurrence and no-recurrence groups (clinical T stage; P = 0.045, clinical N stage; P = 0.002). Univariable Cox regression revealed statistical significance in the clinical T stage (P = 0.049) and clinical N stage (P = 0.010), while multivariable Cox regression demonstrated non-significance in the clinical T stage (P = 0.320) and clinical N stage (P = 0.073).ConclusionResults in this study showed that clinical T, clinical N stage, and molecular subtypes were not statistically significant predictors of recurrence in patients who achieved pCR after NAC. In spite of that, pCR after NAC may be more important than clinical staging and molecular subtype in early breast cancer. In addition, escalated treatments for patients with HER2 + or triple-negative tumors would be considered with a strict patient selection strategy to prevent over-treatment as well as achieve pCR.

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:ObjectivesTrastuzumab (H) and pertuzumab (P) with standard chemotherapy is approved for use in the neoadjuvant setting for human epidermal growth receptor 2 -positive patients. A retrospective analysis was performed of patients treated with dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T), trastuzumab, and pertuzumab (THP) in the neoadjuvant setting. Here, the pathologic complete response (pCR) rates are reported.MethodsAn electronic medical record review was conducted of patients treated with HP-based therapy in the neoadjuvant setting from September 1, 2013, to March 1, 2015. Data on patient demographics, stage of breast cancer, pathology reports, surgical data, and information on systemic therapy were collected. The pCR was defined as total (tpCR, ypT0/is ypN0), German Breast Group (GBG) pCR (ypT0 ypN0), breast pCR (bpCR) with in situ disease (ypT0/is) and without in situ disease (ypT0), and explored axillary pCR (ypN0).ResultsCharts from 66 patients were reviewed, and 57 patients were evaluable for pCR. Median age was 46 years (range 26-68 years). Median tumor size was 4 cm. Of 57 patients, 53 (93%) had operable breast cancer (T1-3, N0-1, M0). Three patients (5.3%) had locally advanced disease (T2-3, N2-3, M0 or T4a-c, any N, M0), and 1 (1.7%) had inflammatory breast cancer (T4d, any N, M0). Overall, 44 (77%) and 13 (23%) had hormone receptor (HR)-positive and negative diseases, respectively. Median numbers of cycles of neoadjuvant treatment were as follows: AC (4, range 1-4), T (4, range 1-4), trastuzumab (6, range 3-8), and pertuzumab (6, range 2-8). In these 57 patients, the rates of tpCR and bpCR with in situ disease were demonstrated in 41/57 (72%) patients, and the rates of GBG pCR and bpCR without in situ disease were found in 30/57 (53%) patients. Of 26 patients with biopsy-proven lymph nodal involvement, axillary pCR occurred in 22 (85%) patients.ConclusionAt a single center, the tpCR and GBG pCR rates of dd AC followed by THP are high at 72% and 53%, respectively. The Oncologist 2017;22:139-143Implications for Practice: This is the first study describing the role of doxorubicin and cyclophosphamide followed by paclitaxel and dual anti-HER2 therapy with trastuzumab and pertuzumab (ACTHP) in patients with early stage HER2-positive breast cancer. Total (breast + lymph node) pathological complete remission (pCR) remission (ypT0/is ypN0) and German Breast Group pCR rates (ypT0/ ypN0) were high at 72% and 53%, respectively, with the ACTHP regimen. Rate of axillary clearance in patients with known axillary involvement was high at 85%, which may translate into less extensive axillary surgeries in this subset in the future.

Project description:BackgroundPatients with a rectal foreign body (RFB) are still a rare entity in general surgery departments but with an increasing incidence over the last years. This case is sometimes difficult to treat, and due to a lack of standardized treatment options, the aim of the study was to present our clinical experiences with the diagnostic and therapeutic approach to RFBs and a review of the currently available literature.Materials and methodsData were collected retrospectively from the patient's records of 20 patients who were treated due to an RFB between 2006 and 2016. Patient's demographics, circumstances of insertion, inserted objects, clinical presentation, laboratory and imaging results, as well as surgical treatment and duration of hospital stay were analyzed. Additionally, a review of the literature was performed with the search items "rectal foreign body" and "surgical therapy". Because many publications were just case reports, we did not perform a meta-analysis or a systematic review.ResultsTwenty-two cases in 20 patients (80% male) presented to the emergency room. The mean age was 38.5±13.7 years. In 68.2% of the cases, the cause of RFB was due to sexual preferences. The following objects were inserted: six dildos, three vibrators, two bottles, one glass, one deodorant, one apple, one fever thermometer, multiple glass fragments and razor blades in one patient and six unknown objects. For 18 RFBs, manual peranal removal without anesthesia was possible in the emergency room, but two patients required intravenous analgesia. Two patients were transferred to the operating room and the foreign body was removed via the anus under general anesthesia. Open surgery with a laparotomy was necessary for two complicated cases. One patient was in need of surgery due to a vacuum generated by the RFB, whereas the second patient suffered from a sigmoid perforation. In all cases, there was no morbidity or mortality.ConclusionIn most cases, the removal of an RFB can be performed peranally in the emergency room without further complications, therefore representing the therapy of choice for RFB. Only in cases with perforation, acute abdomen, or failed peranal approaches, surgery is indicated to remove the foreign body.

Project description:PurposePathologic complete response (pCR) is a critical factor in determining whether patients with rectal cancer (RC) should have surgery after neoadjuvant chemoradiotherapy (nCRT). Currently, a pathologist's histological analysis of surgical specimens is necessary for a reliable assessment of pCR. Machine learning (ML) algorithms have the potential to be a non-invasive way for identifying appropriate candidates for non-operative therapy. However, these ML models' interpretability remains challenging. We propose using explainable boosting machine (EBM) to predict the pCR of RC patients following nCRT.MethodsA total of 296 features were extracted, including clinical parameters (CPs), dose-volume histogram (DVH) parameters from gross tumor volume (GTV) and organs-at-risk, and radiomics (R) and dosiomics (D) features from GTV. R and D features were subcategorized into shape (S), first-order (L1), second-order (L2), and higher-order (L3) local texture features. Multi-view analysis was employed to determine the best set of input feature categories. Boruta was used to select all-relevant features for each input dataset. ML models were trained on 180 cases from our institution, with 37 cases from RTOG 0822 clinical trial serving as the independent dataset for model validation. The performance of EBM in predicting pCR on the test dataset was evaluated using ROC AUC and compared with that of three state-of-the-art black-box models: extreme gradient boosting (XGB), random forest (RF) and support vector machine (SVM). The predictions of all black-box models were interpreted using Shapley additive explanations.ResultsThe best input feature categories were CP+DVH+S+R_L1+R_L2 for all models, from which Boruta-selected features enabled the EBM, XGB, RF, and SVM models to attain the AUCs of 0.820, 0.828, 0.828, and 0.774, respectively. Although EBM did not achieve the best performance, it provided the best capability for identifying critical turning points in response scores at distinct feature values, revealing that the bladder with maximum dose >50 Gy, and the tumor with maximum2DDiameterColumn >80 mm, elongation <0.55, leastAxisLength >50 mm and lower variance of CT intensities were associated with unfavorable outcomes.ConclusionsEBM has the potential to enhance the physician's ability to evaluate an ML-based prediction of pCR and has implications for selecting patients for a "watchful waiting" strategy to RC therapy.

Dataset Information

Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma: a single center experience.

Publications

Potential predictive factors for pathologic complete response after the neoadjuvant treatment of rectal adenocarcinoma: a single center experience.

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