Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients.
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ABSTRACT:
SUBMITTER: Wadhwa R
PROVIDER: S-EPMC5572179 | biostudies-literature | 2017 Aug
REPOSITORIES: biostudies-literature
Publications
Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients.
Wadhwa Roopma R Wang Xuemei X Baladandayuthapani Veerabhadran V Liu Bin B Shiozaki Hironori H Shimodaira Yusuke Y Lin Quan Q Elimova Elena E Hofstetter Wayne L WL Swisher Stephen G SG Rice David C DC Maru Dipen M DM Kalhor Neda N Bhutani Manoop S MS Weston Brian B Lee Jeffrey H JH Skinner Heath D HD Scott Ailing W AW Kaya Dilsa Mizrak DM Harada Kazuto K Berry Donald D Song Shumei S Ajani Jaffer A JA
British journal of cancer 20170720 5
<h4>Background</h4>Predictive biomarkers or signature(s) for oesophageal cancer (OC) patients undergoing preoperative therapy could help administration of effective therapy, avoidance of ineffective ones, and establishment new strategies. Since the hedgehog pathway is often upregulated in OC, we examined its transcriptional factor, Gli-1, which confers therapy resistance, we wanted to assess Gli-1 as a predictive biomarker for chemoradiation response and validate it.<h4>Methods</h4>Untreated OC ...[more]
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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.
| S-EPMC9771385 | biostudies-literature
Project description:ObjectiveTo evaluate whether pCR exclusively defines major pathologic response to treatment with improved survival.Summary background datapCR after trimodality therapy for EAC is infrequent but associated with improved prognosis. Yet most clinical trials and correlative studies designate pCR as the primary endpoint.MethodsWe analyzed our prospectively maintained database for patients who underwent trimodality therapy for locally advanced esophageal adeno-carcinoma between 1995 and 2017. Overall survival (OS) was examined by percentage TR in the primary tumor bed and pathologic nodal stage (ypN0) using Kaplan-Meier plots. Optimal thresholds of TR for differentiating patients in terms of OS were investigated with descriptive plots using restricted cubic spline functions; associations were quantified using Cox multivariable analysis.ResultsAmong 788 patients, median follow-up was 37.5 months (range, 0.4210.6); median OS was 48.3 months (95% CI, 42.2-58.8). Absence of residual nodal disease was independently associated with improved survival ( P < 0.001). Survival curves for 90% to 99% TR and 100% TR were similar, and a change in probability of improved OS was observed at 90% TR. On multivariable analysis, combining 90% to 99% and 100% TR was independently associated with improved OS, compared with 50% to 89% and <50% TR.ConclusionsypN0 status is the strongest indicator of major pathologic response to trimodality therapy, in addition to >90% TR in the primary tumor bed. These findings may allow the definition of major pathologic response to be expanded, from pCR to > 90% TR and ypN0. This has meaningful implications for future clinical trials and correlative studies.
| S-EPMC8126574 | biostudies-literature
Project description:Approximately 25% of patients with esophageal cancer (EC) who undergo preoperative chemoradiation, achieve a pathologic complete response (pathCR). We hypothesized that a model based on clinical parameters could predict pathCR with a high (?60%) probability.We analyzed 322 patients with EC who underwent preoperative chemoradiation. All the patients had baseline and postchemoradiation positron emission tomography (PET) and pre- and postchemoradiation endoscopic biopsy. Logistic regression models were used for analysis, and cross-validation via the bootstrap method was carried out to test the model.The 70 (21.7%) patients who achieved a pathCR lived longer (median overall survival [OS], 79.76 months) than the 252 patients who did not achieve a pathCR (median OS, 39.73 months; OS, P = 0.004; disease-free survival, P = 0.003). In a logistic regression analysis, the following parameters contributed to the prediction model: postchemoradiation PET, postchemoradiation biopsy, sex, histologic tumor grade, and baseline (EUS)T stage. The area under the receiver-operating characteristic curve was 0.72 (95% confidence interval [CI] 0.662-0.787); after the bootstrap validation with 200 repetitions, the bias-corrected AU-ROC was 0.70 (95% CI 0.643-0.728).Our data suggest that the logistic regression model can predict pathCR with a high probability. This clinical model could complement others (biomarkers) to predict pathCR.
| S-EPMC3457750 | biostudies-other
Project description:The response to neoadjuvant chemoradiation therapy is an important prognostic factor for locally advanced rectal cancer. Although the majority of the patients after neoadjuvant therapy are referred to following surgery, the clinical data show that complete clinical or pathological response is found in a significant proportion of the patients. Diagnostic accuracy of confirming the complete response has a crucial role in further management of a rectal cancer patient. As the rate of clinical complete response, unfortunately, is not always consistent with pathological complete response, accurate diagnostic parameters and predictive markers of tumor response may help to guide more personalized treatment strategies and identify potential candidates for nonoperative management more safely. The management of complete response demands interdisciplinary collaboration including oncologists, radiotherapists, radiologists, pathologists, endoscopists and surgeons, because the absence of a multidisciplinary approach may compromise the oncological outcome. Prediction and improvement of rectal cancer response to neoadjuvant therapy is still an active and challenging field of further research. This literature review is summarizing the main, currently known clinical information about the complete response that could be useful in case if encountering such condition in rectal cancer patients after neoadjuvant chemoradiation therapy, using as a source PubMed publications from 2010-2021 matching the search terms "rectal cancer", "neoadjuvant therapy" and "response".
| S-EPMC8537499 | biostudies-literature
Project description:PURPOSE:To examine the value of early changes in quantitative diffusion-weighted imaging and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for discriminating complete pathologic response (pCR) to chemoradiation in esophageal cancer. METHODS AND MATERIALS:Twenty esophageal cancer patients treated with chemoradiation followed by surgery were prospectively enrolled. Patients underwent magnetic resonance imaging and FDG-PET/CT scans at baseline, interim (2 weeks after chemoradiation start), and first follow-up. On the basis of pathologic findings at surgery, patients were categorized into tumor regression groups (TRG1, TRG2, and TRG3+). Distributions of summary statistics in apparent diffusion coefficient (ADC) and FDG-PET at baseline and relative changes at interim and follow-up scans were compared between pCR/TRG1 and non-pCR/TRG2+ groups and across readers. Receiver operating characteristics were evaluated for summary measures to characterize discrimination of pCR from non-pCR. RESULTS:Relative changes in tumor volume ADC (?ADC) mean and 25th and 10th percentiles from baseline to interim were able to completely discriminate (area under the curve = 1, P < .0011) between pCR and non-pCR (thresholds = 27.7%, 29.2%, and 32.1%, respectively) and were found to have high interreader reliability (95% limits of agreement of 1.001, 0.944, and 0.940, respectively). Relative change in total lesion glycolysis (TLG) from baseline to interim was significantly different among pCR and non-pCR groups (P=.0117) and yielded an area under the curve of 0.947 (95% confidence interval 0.8505-1.043). An optimal threshold of 59% decrease in TLG provided optimal sensitivity (specificity) of 1.000 (0.867). Changes in ADC summary measures were negatively correlated with that of TLG (Spearman, -0.495, P=.027). CONCLUSIONS:Quantitative volume ?ADC and TLG during treatment may serve as early imaging biomarkers for discriminating pathologic response to chemoradiation in esophageal cancer. Validation of these data in larger, prospective, multicenter studies is essential.
| S-EPMC6119639 | biostudies-literature
Project description:BackgroundTo retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients.MethodsA multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7-12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively.ResultsData on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001), respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while 3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p < 0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001) were significantly correlated to pCR. The positive impact of interval (p < 0.001) was confirmed at multivariate analysis as the only correlated factor.ConclusionWe confirmed on a population-level that lengthening the interval (>13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.
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Project description:BackgroundTo investigate the association of axillary pathologic complete response (pCR) rate among breast cancer patients with pCR after neoadjuvant chemotherapy (NCT).MethodsThe retrospective clinical data of 1,903 patients who were treated with NCT between March, 2010 and December, 2018, were collected from one Chinese database and analyzed. The correlations between clinicopathological characteristics and breast pCR with axillary pCR were calculated by χ2 test. Binary logistic regression analysis was used for multivariate analysis. The relative risk of positive axillary nodes after NCT in patients with and without breast pCR was analyzed using a Cochran-Mantel-Haenszel (CMH) test stratified by initial N stage and tumor subtype.ResultsThe rate of axillary pCR was increased in the cases with initial cN0, Ki67 high expression, HR+HER2+/HR-HER2+/TN subtypes, and breast pCR. After NCT, the relative risk of nodal disease burden was 4.81 in patients without breast pCR compared with patients with breast pCR. The relative risk of positive nodal status in patients with cN0, cN1, cN2, and cN3 disease without vs. with breast pCR was 6.45, 4.88, 5.69 and 6.24, respectively. The relative risk of positive nodal status in patients with HR+HER2-, HR+HER2+, HR-HER2+, and TN disease was 4.02, 4.50, 3.82 and 4.18, respectively. Of cN0 patients with breast pCR, only 4 out of 44 (9%) with HER2-positive disease had 1 or 2 axillary lymph node metastases at final surgical pathology compared to 30 out of 98 (31%) of those without breast pCR. There was no evidence of positive nodal residue among all 21 patients (100%) with TN disease compared to 65% (36 of 55) of patients without breast pCR.ConclusionsNodal status is strongly correlated with breast pCR after NCT. Patients with initial cN0/1 TN/HER2 positive disease who achieve breast pCR at surgery have a low risk of nodal metastasis. These results suggest that the failure rate of missing positive lymph nodes among those patients was very low and that it is safe for such patients to undergo sentinel lymph node biopsy (SLNB) after NCT. This study also provides a theoretical basis for clinical trials focused on the avoidance of axillary surgery in selected patients.
| S-EPMC7475504 | biostudies-literature
Project description:BackgroundAnti-EGFR-based therapies have limited success in HNSCC patients. Predictive biomarkers are greatly needed to identify the patients likely to be benefited from these targeted therapies. Here, we present the prognostic and predictive association of biomarkers in HPV-negative locally advanced (LA) HNSCC patients.MethodsTreatment-naive tumour tissue samples of 404 patients, a subset of randomised Phase 3 trial comparing cisplatin radiation (CRT) versus nimotuzumab plus cisplatin radiation (NCRT) were analysed to evaluate the expression of HIF1α, EGFR and pEGFR by immunohistochemistry and EGFR gene copy change by FISH. Progression-free survival (PFS), locoregional control (LRC) and overall survival (OS) were estimated by Kaplan-Meier method. Hazard ratios were estimated by Cox proportional hazard models.ResultsBaseline characteristics of the patients were balanced between two treatment groups (CRT vs NCRT) and were representative of the trial cohort. The median follow-up was of 39.13 months. Low HIF1α was associated with better PFS [HR (95% CI) = 0.62 (0.42-0.93)], LRC [HR (95% CI) = 0.56 (0.37-0.86)] and OS [HR (95% CI) = 0.63 (0.43-0.93)] in the CRT group. Multivariable analysis revealed HIF1α as an independent negative prognostic biomarker. For patients with high HIF1α, NCRT significantly improved the outcomes [PFS:HR (95% CI) = 0.55 (0.37-0.82), LRC:HR (95% CI) = 0.55 (0.36-0.85) and OS:HR (95% CI) = 0.54 (0.36-0.81)] compared to CRT. While in patients with low HIF1α, no difference in the clinical outcomes was observed between treatments. Interaction test suggested a predictive value of HIF1α for OS (P = 0.008).ConclusionsHigh HIF1α expression is a predictor of poor clinical response to CRT in HPV-negative LA-HNSCC patients. These patients with high HIF1α significantly benefited with the addition of nimotuzumab to CRT.Clinical trial registrationRegistered with the Clinical Trial Registry of India (Trial registration identifier-CTRI/2014/09/004980).
| S-EPMC7722894 | biostudies-literature
Project description:BackgroundTo analyze clinical characteristics in the prediction of death within 1 year in advanced oropharyngeal cancer patients treated with chemoradiation.MethodsOne hundred forty-seven advanced oropharyngeal cancer patients who underwent curative-intent chemoradiation treatment were retrospectively enrolled. The pre-treatment clinical parameters including inflammatory markers were reviewed.ResultsThe 1-year death rate for all patients was 29% [95% confidence interval (CI): 23-37%]. In multivariate logistic regression analysis, hemoglobulin (Hb) < 13.5 g/dl was an independent indicator of death within 1-year [Odds ratio (OR) 5.85, 95% CI 2.17-15.75, p < 0.001]. Systemic immune inflammation (SII) ≥ 1820 was also a significant factor for prediction of death within 1 year (OR 4.78, 95% CI 1.44-15.85, p = 0.011). We further used gander, age, Hb and SII to develop a nomogram to predict death within 1 year. The c-index of the model was 0.75 (95%CI 0.66-0.83). For patients with low nomogram score (< 14) versus high nomogram score (≥ 14), the 1-year and 2-year OS rates were 91 and 71% versus 53 and 29%, respectively. (p < 0.001). A difference in the disease persistence or recurrence rate between patients with high and low nomogram score was significant (73 and 28%, respectively; p < 0.001).ConclusionsThe pre-treatment Hb < 13.5 g/dl and SII ≥ 1820 are associated with higher risks of death within 1-year in patients with advanced oropharyngeal cancers. Nomogram can aid in patient counseling and treatment modality adjustment. The development of a more effective treatment protocol for patients with high nomogram score will be essential.
| S-EPMC9167527 | biostudies-literature
Project description:To identify predictors of long-term outcome for patients with clinical complete response (cCR) after definite chemoradiotherapy (CRT) or radiation therapy (RT) for oesophageal cancer (EC).In this retrospective study, we reviewed the files of all patients from our institution that underwent definitive RCT or RT for EC, from January 1998 to December 2003. Among 402 consecutive patients with EC, 110 cCR responses were observed, i.e. without evidence of tumour on morphological examination of the biopsy specimens, 8 to 10 weeks after radiation. Baseline patient and tumour characteristics were as follows: male?=?98/110, median age?=?60, squamous histology?=?103/110, tumour site (upper/middle/lower third)?=?41/50/19, weight loss none/<10%/?10%?=?36/45/29, dysphagia grade 1/2/?3?=?30/14/66. Patients were staged according to endosonography and/or computed tomography. There were 9 stage I, 31 stage IIA, 15 stage IIB, 41 stage III, 6 stage IV. Post treatment nutritional characteristics were as follows: weight loss during treatment none/<10%???10%?=?35/38/37, remaining dysphagia grade 1/2/?3?=?54/24/32. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method.During follow up (median: 6 [0.4-9.8] years), 16 patients had salvage surgery. Median OS was 2.5 years, and 5-year OS was 33.5%. Histological type, stage, age, gender, and treatment characteristics had no significant impact on outcome. The risk of death was increased two-fold for patients with grade???3 dysphagia after treatment (HR?=?1.9 [1.2-3.1], p?=?0.007). Weight loss ?10% during treatment also negatively affected outcome (HR?=?1.8 [1.0-3.2], p?=?0.040).One EC patient among 3 with cCR after definite CRT/RT is still alive at 5 years. Variables related to reduced OS were: remaining significant dysphagia after treatment and weight loss ?10% during treatment.
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