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Development of a Nomogram Model for Treatment of Elderly Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

ABSTRACT: (1) Purpose: This study aims to explore risk-adapted treatment for elderly patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) according to their pretreatment risk stratification and the degree of comorbidity. (2) Methods: A total of 583 elderly LA-NPC patients diagnosed from January 2011 to January 2018 are retrospectively studied. A nomogram for disease-free survival (DFS) is constructed based on multivariate Cox regression analysis. The performance of the model is evaluated by using the area under the curve (AUC) of the receiver operating characteristic curve and Harrell concordance index (C-index). Then, the entire cohort is divided into different risk groups according to the nomogram cutoff value determined by X-tile analysis. The degree of comorbidities is assessed by the Charlson Comorbidity Index (CCI). Finally, survival rates are estimated and compared by the Kaplan-Meier method and the log-rank test. (3) Results: A nomogram for DFS is constructed with T/N classification, Epstein-Barr virus DNA and albumin. The nomogram shows well prognostic performance and significantly outperformed the tumor-node-metastasis staging system for estimating DFS (AUC, 0.710 vs. 0.607; C-index, 0.668 vs. 0.585; both p < 0.001). The high-risk group generated by nomogram has significantly poorer survival compared with the low-risk group (3-year DFS, 76.7% vs. 44.6%, p < 0.001). For high-risk patients with fewer comorbidities (CCI = 2), chemotherapy combined with radiotherapy is associated with significantly better survival (p < 0.05) than radiotherapy alone. (4) Conclusion: A prognostic nomogram for DFS is constructed with generating two risk groups. Combining risk stratification and the degree of comorbidities can guide risk-adapted treatment for elderly LA-NPC patients.

SUBMITTER: Kou J

PROVIDER: S-EPMC8618502 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceBecause of tumor heterogeneity, overall survival (OS) differs significantly among individuals with nasopharyngeal carcinoma (NPC), even among those with the same clinical stage. Relying solely on TNM staging to guide treatment remains imperfect.ObjectivesTo establish a comprehensive nomogram to estimate individualized OS and to explore stratified treatment regimens for risk subgroups in nonmetastatic NPC.Design, setting, and participantsThis cohort study included 8093 patients diagnosed with NPC at a single center in China from April 2009 to December 2015. The sample was split into a training cohort (5398 participants [66.7%]) and validation cohort (2695 [33.3%]). Data were analyzed in May 2020.ExposuresAge, T stage, N stage, Epstein-Barr virus (EBV) DNA level, serum lactate dehydrogenase (LDH) levels, and albumin (ALB) levels.Main outcomes and measuresThe primary end point was OS. The nomogram for estimating OS was generated based on multivariate Cox proportional hazards regression. The performance of the nomogram was quantified using Harrell concordance index (C index), the area under the curve (AUC) of the receiver operating characteristic curve, and a calibration curve. OS rates were established using the Kaplan-Meier method, and intersubgroup differences were examined by the log-rank test.ResultsAmong the 8093 participants, 5688 (70.3%) were men, and the median age at diagnosis was 45 years (range, 7-85 years). Six variables (age, T stage, N stage, EBV DNA levels, LDH levels, and ALB levels) were identified through multivariate Cox regression and incorporated into a nomogram to estimate OS. The resulting nomogram showed excellent discriminative ability and significantly outperformed the eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for estimating OS (C index, 0.716 [95% CI, 0.698-0.734] vs 0.643 [95% CI, 0.624-0.661]; P < .001; AUC, 0.717 [95% CI, 0.698-0.737] vs 0.643 [95% CI, 0.623-0.662]; P < .001), and the calibration curves showed satisfactory agreement between the actual and nomogram-estimated OS rates. The validation cohort confirmed the results. Patients were stratified into 4 risk groups based on the 25th, 50th, and 75th percentile score values estimated from the nomogram. The 4 nomogram-defined risk groups demonstrated significantly different intergroup OS (3-year OS rates: risk group 1, 1328 of 1345 [98.7%]; risk group 2, 1289 of 1341 [96.1%]; risk group 3, 1222 of 1321 [92.5%]; risk group 4, 1173 of 1391 [84.3%]; P < .001). These risk groups were associated with the efficacy of different treatment regimens. For example, for risk group 4, induction chemotherapy with concurrent chemoradiotherapy was associated with a significantly better OS than concurrent chemoradiotherapy (log-rank P = .008) and intensity-modulated radiotherapy alone (log-rank P < .001).Conclusions and relevanceIn this study, the proposed nomogram model enabled individualized prognostication of OS and could help to guide risk-adapted treatment for patients with nonmetastatic NPC.

Project description:BACKGROUND: To clarify the feasibility and efficacy of chemoradiotherapy (CRT) in elderly (age?65 years) patients with locoregionally advanced nasopharyngeal carcinoma (NPC). METHODS: From January 2000 to December 2006, 101 newly diagnosed elderly non-metastatic NPC patients (age?65 years) who received cisplatin 3-weekly or weekly concurrent CRT with/without sequential chemotherapy were recruited. Each patient from the CRT group was matched to another patient treated with radiotherapy (RT) alone based on age, gender, pathological type, performance status, overall stage, stage method, Adult Comorbidity Evaluation-27 (ACE-27) score and RT technique, from the same institute and time period. We also recruited 101 young patients (age<65 years) as the referent group, which had been matched to the CRT group based on patient characteristics and treatment parameters. Treatment tolerability and toxicity were clarified, and treatment outcomes were calculated and compared among groups. RESULTS: CRT was feasible in elderly NPC patients, while a concurrent regimen of weekly cisplatin was more tolerable. Grade?3 acute toxicity in CRT group was similar with referent group, although it was significantly higher than the RT alone group (65.3% vs. 43.6%, P=0.002). Furthermore, patients with ACE-27 score?2 in the CRT group had significantly higher severe acute toxicity and dose reduction. Survival was poorer in elderly patients than the referent group. Compared to RT alone, CRT significantly improved the 5-year overall survival (OS: 54.6% vs. 39.3%, P=0.009), cancer-specific survival (CSS: 56.6% vs. 42.7%, P=0.022), disease-free survival (DFS: 51.6% vs. 30.2%, P=0.028) and locoregional relapse-free survival (LRRFS: 78.4% vs. 52.2%, P=0.003), but not distant metastasis-free survival (DMFS: 69.6% vs. 63.6%, P=0.669). However, CRT did not significantly improve 5-year OS (43.6% vs. 27.3%, P=0.893) or CSS (43.6% vs. 34.1%, P=0.971) in elderly NPC patients with ACE-27 score?2. CONCLUSIONS: CRT is feasible and effective in elderly patients with locoregionally advanced NPC without severe comorbidities. CRT should be used under serious consideration and be further tested in elderly patients with severe comorbidities. As such, it is essential to perform a comprehensive evaluation of pretreatment comorbidity status for all elderly NPC patients.

Project description:BackgroundThis study aims to investigate the prognostic value of changes in hematological and inflammatory markers during induction chemotherapy (IC) and concurrent chemo-radiation (CCRT), thus construct nomograms to predict progression free survival (PFS) of patients with locally advanced nasopharyngeal carcinoma (LANPC).Methods130 patients were included in this prospective analysis. Univariate and multivariate cox regression analyses were conducted to identify prognostic factors. Three multivariate analyses integrating different groups of variables were conducted independently. Concordance indexes (c-index), calibration plots and Kaplan-Meier curves were used to evaluate the nomograms. Bootstrap validation was performed to determine the accuracy of the nomogram using 1000 resamples. The performances of proposed nomograms and TNM staging system were compared to validate the prognostic value of hematological and inflammatory markers.ResultsPretreatment gross tumor volume of nodal disease (GTVn), Δe/bHGB (hemoglobin count at end of treatment/baseline hemoglobin count), and stage were selected as predictors for 3-year PFS in first multivariate analysis of clinical factors. The second multivariate analysis of clinical factors and all hematological variables demonstrated that ΔminLYM (minimum lymphocyte count during CCRT/lymphocyte count post-IC), pretreatment GTVn and stage were associated with 3-year PFS. Final multivariate analysis, incorporating all clinical factors, hematological variables and inflammatory markers, identified the following prognostic factors: pretreatment GTVn, stage, ΔmaxPLR (maximum platelet-to-lymphocyte ratio (PLR) during CCRT/PLR post-IC), and ΔminPLT (minimum platelet count during CCRT/platelet count post-IC). Calibration plots showed agreement between the PFS predicted by the nomograms and actual PFS. Kaplan-Meier curves demonstrated that patients in the high-risk group had shorter PFS than those in the low-risk group (P ≤ 0.001). The c-indexes of the three nomograms for PFS were 0.742 (95% CI, 0.639-0.846), 0.766 (95% CI, 0.661-0.871) and 0.815 (95% CI,0.737-0.893) respectively, while c-index of current TNM staging system was 0.633 (95% CI, 0.531-0.736).ConclusionWe developed and validated a nomogram for predicting PFS in patients with LANPC who received induction chemotherapy and concurrent chemo-radiation. Our study confirmed the prognostic value of dynamic changes in hematological and inflammatory markers. The proposed nomogram outperformed the current TNM staging system in predicting PFS, facilitating risk stratification and guiding individualized treatment plans.

Project description:There is no standard third-line or further systemic treatment for patients with inoperable locoregionally advanced recurrent or metastatic nasopharyngeal carcinoma (NPC). Metronomic oral cyclophosphamide provides an acceptable and cheap option for these heavily pretreated patients who had limited choices. We conducted a prospective phase II single-arm open-label study of metronomic oral cyclophosphamide. Patients with locoregionally advanced recurrent inoperable (rT3/T4, rN2-N3b) or metastatic (rM1) NPC who had Eastern Cooperative Oncology Group (ECOG) performance status (PS) (0-2) and had progressed after at least 2 lines of palliative systemic chemotherapy were eligible. They received oral cyclophosphamide between 50 and 150 mg once daily until progressive disease or unacceptable toxicity. Objective response rate (ORR), disease control rate (DCR), biochemical response (two consecutive declines of plasma EBV DNA after treatment), progression-free survival (PFS), overall survival (OS), and safety profiles were evaluated. A total of 56 patients were recruited. Thirty-three, 13, 6, 3, and 1 patients received cyclophosphamide as 3rd, 4th, 5th, 6th, and 7th line of therapy respectively. After a median follow-up of 9.95 months (range 1.76-59.51 months), the ORR was 8.9% and the DCR was 57.1%. The median PFS and OS were 4.47 and 9.20 months, respectively. Those with PS 1 had longer median PFS (5.49 months) compared to those with PS 2 (3.75 months, P = .011). Besides, those who had locoregionally recurrent disease had better PFS (8.97 months, 95% CI, 0.53-17.41 months) compared to those who had distant metastases (4.14 months, 95% CI, 2.53-5.75 months, P = .020). Multivariable analysis revealed that PS 1 (vs 2) (P = .020) and locoregional recurrence (vs metastasis) (P = .029) were the only significant independent prognostic factors of PFS. Around 16 (28.6%) patients developed grade ≥3 adverse events, including malaise (5.4%), hematological (8.9%), gastrointestinal (3.6%), feverish (3.6%), and hemorrhagic (1.8%) events. The median cost of the whole drug treatment was 51.65 US dollars (USD) (range 4.15-142.75 USD) (1 USD = 7.8 HK dollars [HKD]). Metronomic oral cyclophosphamide is an acceptable third-line or beyond systemic therapy for locoregionally advanced recurrent or metastatic NPC with acceptable toxicity and limited financial burden.

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Development of a Nomogram Model for Treatment of Elderly Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

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