A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.
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ABSTRACT:
SUBMITTER: Fang XL
PROVIDER: S-EPMC11301085 | biostudies-literature | 2024 Aug
REPOSITORIES: biostudies-literature
Publications
A radiogenomic clinical decision support system to inform individualized treatment in advanced nasopharyngeal carcinoma.
Fang Xue-Liang XL Zhong Lian-Zhen LZ Jiang Wei W Huang Cheng-Long CL Lei Yuan Y Tang Si-Qi SQ Li Qing-Jie QJ Liu Li-Zhi LZ Tian Li L Li Ying-Qin YQ Chen Yu-Pei YP Lin Li L Guo Rui R Li Wen-Fei WF Tian Jie J Liu Na N Dong Di D Ma Jun J Tang Ling-Long LL
iScience 20240629 8
Both concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT) followed by CCRT are standard care of advanced nasopharyngeal carcinoma (NPC). However, tailoring personalized treatment is lacking. Herein, we established a radiogenomic clinical decision support system to classify patients into three subgroups according to their predicted disease-free survival (DFS) with CCRT and ICT response. The CCRT-preferred group was suitable for CCRT since they achieved good survival with CCRT, whi ...[more]
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Project description:BackgroundThe role of pretreatment Epstein-Barr virus DNA (pre-DNA) for individualized induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) still remains unknown. We aimed to address this clinical issue.MethodsIn total, data on 6218 patient with newly diagnosed LA-NPC receiving concurrent chemoradiotherapy (CCRT) with or without IC were retrospectively reviewed. Receiver operating characteristics (ROC) curve was adopted to calculate the cut-off value of pre-DNA based on disease-free survival (DFS). Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes between IC + CCRT and CCRT groups were compared.ResultsAmong the original cohort, no survival difference between IC + CCRT and CCRT groups was found. The cut-off value of pre-DNA was 4650 copies/ml (area under curve [AUC], 0.620; sensitivity, 0.6224; specificity, 0.5673). For patients with Pre-DNA ≤ 4650 copies/ml, the IC + CCRT and CCRT groups also achieved comparable survival outcomes (P > 0.05 for all rates). However, IC + CCRT was associated with significantly improved 3-year DFS (78.6% vs. 74.8%, P = 0.03), overall survival (OS; 91.4% vs. 87.5%, P = 0.002) and distant metastasis-free survival (DMFS; 86.0% vs. 82.2%, P = 0.036) for patient with pre-DNA > 4650 copies/ml. Multivariate analysis also confirm that IC + CCRT was an independent prognostic factor for DFS (HR, 0.817; 95% CI, 0.683-0.977; P = 0.027), OS (HR, 0.675; 95% CI, 0.537-0.848; P = 0.001) and DMFS (HR, 0.782; 95% CI, 0.626-0.976; P = 0.03).ConclusionsPre-DNA may be a feasible and powerful consideration for individualized IC apart from other baseline clinical characteristics in LA-NPC.
| S-EPMC6299978 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) has seen improved treatment outcomes and a decrease in incidence worldwide in recent years due to developments in medicine and improved public health. However, 70% of cases are still diagnosed at advanced stages and these advanced NPC cases show a poor prognosis. Reports on current and future treatment in advanced NPC are summarized. Chemoradiotherapy is the mainstay of treatment for advanced NPC. The administration of platinum agents as a concurrent drug and intensity modulated radiotherapy (IMRT) is the most appropriate irradiation method, and is associated with high local control rates. For induction and adjuvant chemotherapy, platinum-based two- or three-drug combination chemotherapy is recommended. The tumour volume, plasma Epstein-Barr virus (EBV)-DNA levels, and the tumour site are used to determine the indication for adjuvant and neo-adjuvant chemotherapy. The tolerability of induction chemotherapy is controversial, and the indications and timing should be carefully considered in each case. Chemotherapy is used for patients with distant metastasis. Gemcitabine/cisplatin is the first-line regimen. The efficacy of immune checkpoint inhibitor (ICI) treatment has recently been reported for NPC and, as in other areas of the head and neck, it is expected to be effective for patients with recurrent/distant metastasis. Trials are underway for various uses of ICIs, including induction chemotherapy, postoperative treatment, and use in combination with chemoradiotherapy. Immunotherapy for NPC, an EBV-associated cancer, has been reported to have some efficacy with immunotherapy used in other EBV-associated cancers. Immunotherapy may be introduced for NPC in the future, depending on the results of clinical trials. Future changes in the treatment of NPC are expected to include risk classification based on plasma EBV-DNA levels and the development of personalized treatment with individual selection of timing and type of therapy.
| S-EPMC9480178 | biostudies-literature
Project description:BackgroundInduction chemotherapy (ICT) plus concurrent chemoradiotherapy (CCRT) and CCRT alone were the optional treatment regimens in locoregionally advanced nasopharyngeal carcinoma (NPC) patients. Currently, the choice of them remains equivocal in clinical practice. We aimed to develop a deep learning-based model for treatment decision in NPC.MethodsA total of 1872 patients with stage T3N1M0 NPC were enrolled from four Chinese centres and received either ICT+CCRT or CCRT. A nomogram was constructed for predicting the prognosis of patients with different treatment regimens using multi-task deep learning radiomics and pre-treatment MR images, based on which an optimal treatment regimen was recommended. Model performance was assessed by the concordance index (C-index) and the Kaplan-Meier estimator.FindingsThe nomogram showed excellent prognostic ability for disease-free survival in both the CCRT (C-index range: 0.888-0.921) and ICT+CCRT (C-index range: 0.784-0.830) groups. According to the prognostic difference between treatments using the nomogram, patients were divided into the ICT-preferred and CCRT-preferred groups. In the ICT-preferred group, patients receiving ICT+CCRT exhibited prolonged survival over those receiving CCRT in the internal and external test cohorts (hazard ratio [HR]: 0.17, p<0.001 and 0.24, p=0.02); while the trend was opposite in the CCRT-preferred group (HR: 6.24, p<0.001 and 12.08, p<0.001). Similar results for treatment decision using the nomogram were obtained in different subgroups stratified by clinical factors and MR acquisition parameters.InterpretationOur nomogram could predict the prognosis of T3N1M0 NPC patients with different treatment regimens and accordingly recommend an optimal treatment regimen, which may serve as a potential tool for promoting personalized treatment of NPC.FundingNational Key R&D Program of China, National Natural Science Foundation of China, Beijing Natural Science Foundation, Strategic Priority Research Program of CAS, Project of High-Level Talents Team Introduction in Zhuhai City, Beijing Natural Science Foundation, Beijing Nova Program, Youth Innovation Promotion Association CAS.
| S-EPMC8365370 | biostudies-literature
Project description:Background: Recurrence remains one of the key reasons of relapse after the radical radiation for locally advanced nasopharyngeal carcinoma (NPC). Here, the multiple molecular and clinical variables integrated decision tree algorithms were designed to predict individual recurrence patterns (with VS without recurrence) for locally advanced NPC. Methods: A total of 136 locally advanced NPC patients retrieved from a randomized controlled phase III trial, were included. For each patient, the expression levels of 33 clinicopathological biomarkers in tumor specimen, 3 Epstein-Barr virus related serological antibody titer and 5 clinicopathological variables, were detected and collected to construct the decision tree algorithm. The expression level of 33 clinicopathological biomarkers in tumor specimen was evaluated by immunohistochemistry staining. Results: Three algorithm classifiers, augmented by the adaptive boosting algorithm for variable selection and classification, were designed to predict individual recurrence pattern. The classifiers were trained in the training subset and further tested using a 10-fold cross-validation scheme in the validation subset. In total, 13 molecules expression level in tumor specimen, including AKT1, Aurora-A, Bax, Bcl-2, N-Cadherin, CENP-H, HIF-1α, LMP-1, C-Met, MMP-2, MMP-9, Pontin and Stathmin, and N stage were selected to construct three 10-fold cross-validation decision tree classifiers. These classifiers showed high predictive sensitivity (87.2-93.3%), specificity (69.0-100.0%), and overall accuracy (84.5-95.2%) to predict recurrence pattern individually. Multivariate analyses confirmed the decision tree classifier was an independent prognostic factor to predict individual recurrence (algorithm 1: hazard ration (HR) 0.07, 95% confidence interval (CI) 0.03-0.16, P < 0.01; algorithm 2: HR 0.13, 95% CI 0.04-0.44, P < 0.01; algorithm 3: HR 0.13, 95% CI 0.03-0.68, P = 0.02). Conclusion: Multiple molecular and clinicopathological variables integrated decision tree algorithms may individually predict the recurrence pattern for locally advanced NPC. This decision tree algorism provides a potential tool to select patients with high recurrence risk for intensive follow-up, and to diagnose recurrence at an earlier stage for salvage treatment in the NPC endemic region.
| S-EPMC6603411 | biostudies-literature
Project description:Re-irradiation with intensity-modulated radiotherapy (IMRT) remains the primary treatment modality for inoperable locally recurrent nasopharyngeal carcinoma (NPC). However, the rate of radiation-related late adverse effects is often substantially high. Therefore, we aimed to explore failure patterns and individualized treatment plans of re-irradiation for inoperable locally recurrent NPC. Ninety-seven patients who underwent IMRT were retrospectively analyzed. Sixty-two patients had clinical target volume of recurrence (rCTV) delineated, and thirty-five patients had only gross tumor volume of recurrence (rGTV) delineated. Twenty-nine patients developed second local failures after re-irradiation with IMRT (28 cases available). Among those patients, 64.3% (18/28) of patients and 35.7% (10/28) developed in-field or out-field, respectively. No statistical correlation was observed between target volume (rGTV or rCTV) and the local recurrence rate, local failure patterns, grade ≥ 3 toxicity, and survival. Multivariate analysis showed that recurrent T (rT) stage (HR 2.62, P = 0.019) and rGTV volume (HR 1.73, P = 0.037) were independent prognostic factors for overall survival (OS). Risk stratification based on rT stage and rGTV volume revealed that low risk group had a longer 3-year OS rate (66.7% vs. 23.4%), lower total grade ≥ 3 toxicity (P = 0.004), and lower re-radiation associated mortality rates (HR 0.45, P = 0.03) than high risk group. This study demonstrates that the delineation of rCTV may not be beneficial for re-irradiation using IMRT in locally recurrent NPC. Patients with low risk were most suitable for re-irradiation, with maximizing local salvage and minimizing radiation-related toxicities. More precise and individualized plans of re-irradiation are warranted.
| S-EPMC11297266 | biostudies-literature
Project description:BackgroundThe optimal number of cycles of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LANPC) is unclear. We aimed to combine the tumor response during IC and tumor stage to individualize the number of IC cycles.MethodsTotally, 498 LANPC patients who received IC plus CCRT between 2014 and 2018 were reviewed. Tumor response during IC was used to stratify patients with different risks. All patients were classified into those who received two cycles of IC and those who were treated with three cycles. Propensity score matching methods were performed to compare the treatment efficiency.ResultsAfter two cycles of IC, 340/498 (68.3%) cases showed complete tumor response (CR)/partial response (PR) and 158 (31.7%) achieved stable disease (SD)/disease progression (PD). Unfavorable responders (SD/PD) exhibited poor survival outcomes. The three-cycle IC regimen was correlated with better OS and PFS than the two-cycle regimen for N2-3 patients in the CR/PR group. However, the use of different IC cycle strategies achieved similar survival outcomes for SD/PD or N0-1 patients. The incidences of acute toxicities were higher in the IC = 3 group.ConclusionsTumor response during IC could be a powerful predictor of LANPC and could be used to guide the individualized number of IC cycles. A three-cycle IC regimen seemed to be preferable for N2-3 patients who received CR/PR during IC. However, an additional cycle of IC could not benefit N0-1 or SD/PD patients, and the optimal treatment strategies for these patients require further consideration.
| S-EPMC9972137 | biostudies-literature
Project description:Background and objectivesChildren with congenital heart disease (CHD) are at risk of deterioration in the face of common childhood illnesses, and their resuscitation and acute treatment requires guidance of CHD experts. Many children with CHD, however, present to their local emergency departments (ED) with gastrointestinal and respiratory symptoms that closely mimic symptoms of CHD related heart failure. This can lead to incorrect or delayed diagnosis and treatment where CHD expertise is limited. An understanding of the differences in cognitive decision-making processes between CHD experts and ED physicians can inform how best to support ED physicians when treating CHD patients.MethodsCardiac intensivists (CHD experts) and pediatric emergency department physicians (ED physicians) in a major academic cardiac center were interviewed using the critical decision method. Interview transcripts were coded deductively based on Schubert and Klein's macrocognitive frameworks and inductively to allow for new or modified characterization of dimensions.ResultsIn total, 6 CHD experts and 7 ED physicians were interviewed for this study. Although both CHD experts and ED physicians spent a lot of time sensemaking, their approaches to sensemaking differed. CHD experts reported readily recognizing the physiology of complex congenital heart disease and focused primarily on ruling out cardiac causes for the presenting illness. ED physicians reported a delay in attributing the signs and symptoms of the presenting illness to congenital heart disease, because these clinical findings were often non-specific, and thus explored different diagnoses. CHD experts moved quickly to treatment and more time anticipating potential problems and making specific contingency plans, while ED physicians spent more time gathering a range of data prior to arriving at a diagnosis. These findings were then applied to develop a prototype web-based decision support application for patients with CHD.ConclusionThere are differences in the cognitive processes used by CHD experts and ED physicians when managing CHD patients. An understanding of differences in the cognitive processes used by CHD experts and ED physicians can inform the development of potential interventions, such as clinical decision support systems and training pathways, to support decision making pertaining to the acute treatment of pediatric CHD patients.
| S-EPMC8850471 | biostudies-literature
Project description:BackgroundImages from magnetic resonance imaging (MRI) are crucial unstructured data for prognostic evaluation in nasopharyngeal carcinoma (NPC). We developed and validated a prognostic system based on the MRI features and clinical data of locoregionally advanced NPC (LA-NPC) patients to distinguish low-risk patients with LA-NPC for whom concurrent chemoradiotherapy (CCRT) is sufficient.MethodsThis multicenter, retrospective study included 3444 patients with LA-NPC from January 1, 2010, to January 31, 2017. A 3-dimensional convolutional neural network was used to learn the image features from pretreatment MRI images. An eXtreme Gradient Boosting model was trained with the MRI features and clinical data to assign an overall score to each patient. Comprehensive evaluations were implemented to assess the performance of the predictive system. We applied the overall score to distinguish high-risk patients from low-risk patients. The clinical benefit of induction chemotherapy (IC) was analyzed in each risk group by survival curves.ResultsWe constructed a prognostic system displaying a concordance index of 0.776 (95% confidence interval [CI] = 0.746 to 0.806) for the internal validation cohort and 0.757 (95% CI = 0.695 to 0.819), 0.719 (95% CI = 0.650 to 0.789), and 0.746 (95% CI = 0.699 to 0.793) for the 3 external validation cohorts, which presented a statistically significant improvement compared with the conventional TNM staging system. In the high-risk group, patients who received induction chemotherapy plus CCRT had better outcomes than patients who received CCRT alone, whereas there was no statistically significant difference in the low-risk group.ConclusionsThe proposed framework can capture more complex and heterogeneous information to predict the prognosis of patients with LA-NPC and potentially contribute to clinical decision making.
| S-EPMC8096375 | biostudies-literature
Project description:PurposeCetuximab, an anti-epidermal growth factor receptor monoclonal antibody, carries the potential for combination treatment against nasopharyngeal carcinoma (NPC). We conducted a meta-analysis to assess the possible benefits and safety between the combination treatment with cetuximab and conventional treatment in NPC patients. Skin toxicity (ST) associated with additional cetuximab was evaluated as well.MethodsWe performed a systematic search (PubMed, Embase, Cochrane library, China National Knowledge Infrastructure, and WanFang Data) for studies comparing combination treatment with cetuximab versus conventional treatment in NPC patients. The selected studies included completely or partly reported clinical outcomes including survivals, complete and partial responses, and adverse reactions (ST). The pooled HR, relative risk (RR), and respective 95% CI were estimated by using fixed effects model or random effects model.ResultsA total of 23 relevant studies with available data were included in the final analysis. According to the pooled data, combination treatment with cetuximab showed improved efficacy on increased objective response rate (studies with cetuximab treatment: RR: 1.39, 95% CI: 1.29-1.50; concurrent chemoradiotherapy with or without cetuximab: RR: 1.39, 95% CI: 1.25-1.54) and prolonged survival (studies with cetuximab treatment: the pooled HR for OS was 0.70, 95% CI: 0.55-0.89; concurrent chemoradiotherapy with or without cetuximab: the pooled HR for OS was 0.64, 95% CI: 0.49-0.84) compared with conventional treatment. Moreover, the improved efficacy was invariably accompanied by an increased occurrence of ST (studies with cetuximab treatment: RR: 2.46, 95% CI: 1.81-3.34; concurrent chemoradiotherapy with or without cetuximab: RR: 1.84, 95% CI: 1.02-3.31). However, the majority of adverse reactions exhibited similar occurrence rates between the different treatments.ConclusionPatients with NPC receiving additional cetuximab treatment can benefit more from this systemic comprehensive therapy, while the efficiency of conventional treatment for NPC is limited. ST associated with cetuximab may be used as a potential on-treatment marker to guide treatment with cetuximab against NPC.
| S-EPMC6452812 | biostudies-literature
Project description:BackgroundThe role of induction chemotherapy is less clear in non-endemic locally advanced nanopharyngeal carcinomas (NPC).ResultsWith a total of 233 eligible patients and a median follow-up of 36 months, 3-year overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease free survival (DFS) were 84.5%, 94.9%, 78.6% and 69.2%, respectively. The overall failure rate was 21.0% and distant metastasis occurred in 17.2% patients. Multivariate analyses showed that retropharyngeal and bilateral neck lymph node metastasis were significant prognostic factors for DFS and OS. Moreover, patients receiving both GP (gemcitabine+cisplatin) and TP (docetaxel+cisplatin) regimes had significantly higher DFS and OS compared with PF (cisplatin+5-FU) regime. GP regimes lead to significantly improved OS than TP/PF in some subgroup of patients. No severe toxicities were observed.Materials and methodsWe retrospectively analyzed stage III-IVb NPC patients treated between Jan 2006 and Dec 2014, with induction chemotherapy followed by concurrent chemoradiation (IC-CCRT). Statistical analyses were performed on survival and failure patterns.ConclusionsThese results suggested IC-CCRT was safe and effective for NPCs from non-endemic region. The choice of induction regimen appeared to affect patient outcomes.
| S-EPMC5351667 | biostudies-literature