scholarly journals Optimizing the treatment mode for de novo metastatic nasopharyngeal carcinoma with bone-only metastasis

BMC Cancer ◽  
2022 ◽  
Vol 22 (1) ◽  
Author(s):  
Cheng Lin ◽  
Sheng Lin ◽  
Lili Zhu ◽  
Shaojun Lin ◽  
Jianji Pan ◽  
...  

Abstract Background No standard radiotherapy regimens have been established for the treatment of de novo metastatic nasopharyngeal carcinoma (mNPC) with bone-only metastasis. The current study aimed to investigate the efficacy of palliative chemotherapy (PCT) plus locoregional radiotherapy (LRRT) with or without local radiotherapy (RT) for metastatic bone lesions in mNPC. Methods We retrospectively analysed 131 de novo patients with mNPC who had bone-only metastasis and received at least two cycles of PCT with LRRT. The difference in survival was evaluated by the log-rank test. Univariable and multivariable analyses were performed by Cox regression. Results The median overall survival (OS) and progression-free survival (PFS) were 33.0 months and 24.0 months, respectively. Patients with five or fewer metastatic bone lesions had significantly longer OS (72.0 months vs. 23.0 months, Hazard ratios (HR) = 0.45, p <  0.001) and PFS (48.0 months vs. 15.0 months, HR = 0.52, p = 0.004) than those who had more than five metastatic bone lesions. Patients who received four or more cycles of chemotherapy were associated with significantly longer OS (unreached vs. 19.0 months, HR = 0.27, p <  0.001) and PFS (66 months vs. 16.0 months, HR = 0.32, p <  0.001). Multivariate analysis confirmed that fewer bone metastases (≤ 5) and more chemotherapy cycles (≥ 4) were favourable prognostic factors for OS. Subgroup analysis revealed that RT to metastatic bone lesions tended to prolong OS (83.0 months vs. 45.0 months) and PFS (60 months vs. 36.5 months) in patients with five or fewer metastatic bone lesions than in those without RT to metastatic bone lesions (p > 0.05). Patients who received a RT dose > 30 Gy had neither better OS (63.5 months vs. 32.0 months, p = 0.299) nor PFS (48.0 months vs. 28.0 months, p = 0.615) than those who received a RT dose ≤30 Gy. Conclusions Local RT to bone metastases may not significantly improve survival in patients with de novo mNPC with bone-only metastasis who have already received PCT plus LRRT. Receiving four or more cycles of chemotherapy can significantly prolong survival and is a favourable independent protective factor.

2021 ◽  
Author(s):  
Cheng Lin ◽  
Sheng Lin ◽  
li Li Zhu ◽  
jun Shao Lin ◽  
ji Jian Pan ◽  
...  

Abstract Purpose: No standard radiotherapy regimens was established in the treatment of de novo metastatic nasopharyngeal carcinoma (mNPC) with bone-only metastasis. The current study aimed to investigate the efficacy of palliative chemotherapy (PCT) plus locoregional radiotherapy (LLRT) with or without local radiotherapy (RT) to bone metastatic lesions in mNPC, and identify the optimal candidates.Methods: We retrospectively analyzed 141 de novo mNPC patients with bone-only metastasis who received at least two cycles of PCT with or without LLRT and RT to bone metastasis. The difference in survival was evaluated by the log-rank test. Univariable and multivariable analysis was made by Cox regression. Results: Patients who received PCT plus LLRT had significantly longer overall survival (OS) (45.0 months vs 13.5 months, HR = 0.30 , p = 0.001) and progression-free survival (PFS) (29.0 months vs 11.0 months, HR = 0.34, p = 0.014), especially in patients who had less than 3 metastatic bone lesions. Multivariate analysis confirmed that LRRT, more chemotherapy cycles (≥ 4) and limited number of bone metastasis (≤ 3) were favorable prognostic factors for OS. Subgroup analysis revealed that RT to metastatic bones had a tendency to prolong the survival time in the unselected population who received PCT plus LLRT (p > 0.05), while further data suggested that RT to metastatic bones dramatically improve OS (72.0 months vs 26.0 months, p = 0.002) and PFS (60.0 months vs 20.0 months, p = 0.006) for mNPC with less than 3 metastatic bone lesions.Conclusions: LLRT and RT to bone metastatic lesions followed by PCT in de novo mNPC with bone-only metastasis significantly prolonged survival in patients with less than 3 metastatic bone lesions.


2021 ◽  
Author(s):  
Cheng Lin ◽  
Sheng Lin ◽  
lili Zhu ◽  
JianJi Pan ◽  
Yun Xu ◽  
...  

Abstract Purpose: No standard radiotherapy regimens was established in the treatment of de novo metastatic nasopharyngeal carcinoma (mNPC) with bone-only metastasis. The current study aimed to investigate the efficacy of palliative chemotherapy (PCT) plus locoregional radiotherapy (LLRT) with or without local radiotherapy (RT) to bone metastatic lesions in mNPC, and identify the optimal candidates.Methods: We retrospectively analyzed 141 de novo mNPC patients with bone-only metastasis who received at least two cycles of PCT with or without LLRT and RT to bone metastasis. The difference in survival was evaluated by the log-rank test. Univariable and multivariable analysis was made by Cox regression. Results: Patients who received PCT plus LLRT had significantly longer overall survival (OS) (45.0 months vs 13.5 months, HR = 0.30 , p = 0.001) and progression-free survival (PFS) (29.0 months vs 11.0 months, HR = 0.34, p = 0.014), especially in patients who had less than 3 metastatic bone lesions. Multivariate analysis confirmed that LRRT, more chemotherapy cycles (≥ 4) and limited number of bone metastasis (≤ 3) were favorable prognostic factors for OS. Subgroup analysis revealed that RT to metastatic bones had a tendency to prolong the survival time in the unselected population who received PCT plus LLRT (p > 0.05), while further data suggested that RT to metastatic bones dramatically improve OS (72.0 months vs 26.0 months, p = 0.002) and PFS (60.0 months vs 20.0 months, p = 0.006) for mNPC with less than 3 metastatic bone lesions.Conclusions: LLRT and RT to bone metastatic lesions followed by PCT in de novo mNPC with bone-only metastasis significantly prolonged survival in patients with less than 3 metastatic bone lesions.


2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Paul Rogowski ◽  
Christian Trapp ◽  
Rieke von Bestenbostel ◽  
Nina-Sophie Schmidt-Hegemann ◽  
Run Shi ◽  
...  

Abstract Background The aim of this work was to investigate the outcome of metastasis-directed radiotherapy (MDT) in prostate cancer patients with bone metastases following current ESTRO/EORTC subclassifications for oligometastatic disease. Methods Clinical data of 80 consecutive oligometastatic patients with 115 bone lesions receiving MDT between 2011 and 2019 were retrospectively evaluated. Hormone-sensitive (77.5%) and castrate-resistant (22.5%) patients were included. MDT was delivered with conventional fractionated or stereotactic body radiotherapy (SBRT) techniques. Kaplan–Meier method, log rank test, as well as Cox regression were used to calculate local control (LC) and biochemical and clinical progression-free survival (bPFS/cPFS). Results At the time of MDT 31% of patients had de-novo synchronous oligometastatic disease, 46% had de-novo metachronous oligorecurrence after primary treatment and 23% had either de-novo oligoprogressive disease, repeat oligometastatic disease or induced oligometastatic disease. The median BED3 was 93.3 Gy (range 75.8–95.3 Gy). Concomitant ADT was administered in 69% of patients. After a median follow-up of 23 months the median bPFS and cPFS were 16.5 and 21.5 months, respectively. The 2-year LC rate was 98.3%. In multivariate analysis, age ≤ 70 (HR = 2.60, 95% CI 1.20–5.62, p = 0.015) and concomitant ADT (HR = 0.26, 95% CI 0.12–0.58, p = 0.001) significantly correlated with cPFS. Category of oligometastatic disease and hormone-sensitivity were predictive for cPFS in univariate analysis. Of 45 patients with biochemical relapse, nineteen patients (42.2%) had repeat oligometastatic disease. Fourteen patients (31%) underwent a second course of MDT. No patients experienced grade ≥ 3 toxicities. Conclusions MDT is safe and offers high local control rates in bone oligometastases of prostate cancer. At 2 years after treatment, more than 2 out of 5 patients are progression-free. Trial registration Retrospectively registered.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Xiaojing Yang ◽  
Hanru Ren ◽  
Weiwei Yu ◽  
Hongling Li ◽  
Xinmiao Yang ◽  
...  

Objective. To evaluate the prevalence rate and survival situation of bone metastases in initial nasopharyngeal carcinoma (NPC) patients and the hazard and forecast elements of bone metastases NPC patients. Patients and Methods. The data collected from Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2016 were evaluated. Univariate and multivariable logistic analysis and the Cox regression were carried out to estimate predictors and elements of the being of bone metastases at diagnosis, respectively. The overall survival of different subgroups were appraised by log-rank tests and the Kaplan–Meier analysis. Results. Factors including male sex, higher N stage, presence of liver, and brain or lung metastases were largely related to the occurrence of bone metastases. The median survival time for bone metastasis NPC patients was 14.0 months. A factor of more than one primary sequence number predicted worse survival. Conclusion. The data offer corresponding risks and prognostic indicators of bone metastases for NPC patients.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Dan Bao ◽  
Yanfeng Zhao ◽  
Zhou Liu ◽  
Hongxia Zhong ◽  
Yayuan Geng ◽  
...  

Abstract Purpose To explore the value of MRI-based radiomics features in predicting risk in disease progression for nasopharyngeal carcinoma (NPC). Methods 199 patients confirmed with NPC were retrospectively included and then divided into training and validation set using a hold-out validation (159: 40). Discriminative radiomic features were selected with a Wilcoxon signed-rank test from tumors and normal masticatory muscles of 37 NPC patients. LASSO Cox regression and Pearson correlation analysis were applied to further confirm the differential expression of the radiomic features in the training set. Using the multiple Cox regression model, we built a radiomic feature-based classifier, Rad-Score. The prognostic and predictive performance of Rad-Score was validated in the validation cohort and illustrated in all included 199 patients. Results We identified 1832 differentially expressed radiomic features between tumors and normal tissue. Rad-Score was built based on one radiomic feature: CET1-w_wavelet.LLH_GLDM_Dependence-Entropy. Rad-Score showed a satisfactory performance to predict disease progression in NPC with an area under the curve (AUC) of 0.604, 0.732, 0.626 in the training, validation, and the combined cohort (all 199 patients included) respectively. Rad-Score improved risk stratification, and disease progression-free survival was significantly different between these groups in every cohort of patients (p = 0.044 or p < 0.01). Combining radiomics and clinical features, higher AUC was achieved of the prediction of 3-year disease progression-free survival (PFS) (AUC, 0.78) and 5-year disease PFS (AUC, 0.73), although there was no statistical difference. Conclusion The radiomics classifier, Rad-Score, was proven useful for pretreatment prognosis prediction and showed potential in risk stratification for NPC.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 6046-6046
Author(s):  
Sik-Kwan Chan ◽  
Cheng Lin ◽  
Shao Hui Huang ◽  
Tin Ching Chau ◽  
Qiaojuan Guo ◽  
...  

6046 Background: The eighth edition TNM (TNM-8) classified de novo metastatic (metastatic disease at presentation) nasopharyngeal carcinoma (NPC) as M1 without further subdivision. However, survival heterogeneity exists and long-term survival has been observed in a subset of this population. We hypothesize that certain metastatic characteristics could further segregate survival for de novo M1 NPC. Methods: Patients with previously untreated de novo M1 NPC prospectively treated in two academic institutions (The University of Hong Kong [n = 69] and Provincial Clinical College of Fujian Medical University [n = 114] between 2007 and 2016 were recruited and re-staged based on TNM-8 in this study. They were randomized in 2:1 ratio to generate a training cohort (n = 120) and validation cohort (n = 63) respectively. Univariable and multivariable analyses (MVA) were performed for the training cohort to identify the anatomic prognostic factors of overall survival (OS). We then performed recursive partitioning analysis (RPA) which incorporated the anatomic prognostic factors identified in multivariable analyses and derived a new set of RPA stage groups (Anatomic-RPA groups) which predicted OS in the training cohort. The significance of Anatomic-RPA groups in the training cohort was then validated in the validation cohort. UVA and MVA were performed again on the validation cohorts to identify significant OS prognosticators. Results: The training and the validation cohorts had a median follow-up of 27.2 months and 30.2 months, respectively, with the 3-year OS of 51.6% and 51.1%, respectively. Univariable analysis (UVA) and multivariable analysis (MVA) revealed that co-existing liver and bone metastases was the only factor prognostic of OS. Anatomic-RPA groups based on the anatomic prognostic factors identified in UVA and MVA yielded good segregation (M1a: no co-existing liver and bone metastases and M1b: co-existing both liver and bone metastases; median OS 39.5 and 23.7 months respectively; P =.004). RPA for the validation set also confirmed good segregation with co-existing liver and bone metastases (M1a: no co-existing liver and bone metastases and M1b: co-existing liver and bone metastases), with median OS 47.7 and 16.0 months, respectively; P =.008). It was also the only prognostic factor in UVA and MVA in the validation cohort. Conclusions: Our Anatomic-RPA M1 stage groups with anatomical factors provided better subgroup segregation for de novo M1 NPC. The study results provide a robust justification to refine M1 categories in future editions of TNM staging classification.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21032-e21032
Author(s):  
Xuanzong Li ◽  
Linlin Wang

e21032 Background: Previous studies suggested that MET exon 14 ( METex14) mutation regarding as a distinct subset was sensitive to MET-inhibitors, but poorly response to immunotherapy. Conversly, MET non-exon-14 (non-ex14) mutations including those undetermined functions and affecting the kinase or extracellular domains were found to be associated with the resistance to MET-inhibitors. However, therapeutic strategies for MET-non-ex14 mutant cancer are still largely unknown, and the relationship between MET-non-ex14 mutations and the efficacy of immune checkpoint inhibitors (ICIs) has never been reported. Using two public ICIs-treated cohorts, we aimed to assess the role of MET mutations including both METex14 and MET-non-ex14 mutations in NSCLC patients undergoing ICIs therapy. Methods: A total of 385 ICIs-treated NSCLC patients were enrolled to our study. MET mutations were defined as any nonsynonymous mutations, and we divided them into METex14 and MET-non-ex14 mutation subsets according to the mutated-position on MET. Kruskal-Wallis test was used to analyze the difference of tumor mutational burden (TMB) score, and the Fisher’s exact test was applied to compare the rates of durable clinical benefit (DCB). Log-rank test was used to analyze the differences between Kaplan-Meier survival curves. Results: In the entire cohort, we found that 17 patients (17/385, 4.4%) had MET mutations, most of which were pure METex14 mutations (10/17, 58.8%). The median TMB of patients in the entire NSCLC cohort was 6.89 mut/Mb. MET-non-ex14 mutant patients (7/385, 1.8%) possessed a significantly higher TMB than METex14-mutant (10/385, 2.6%) and MET wild-type (368/385, 95.6%) sub-cohorts, respectively (median TMB, 17.92 mut/Mb versus 4.17 mut/Mb, p = 0.008; 17.92 mut/Mb versus 6.96 mut/Mb, p = 0.01, respectively). DCB was more common in patients harbored MET-non-ex14 mutations than patients with METex14 mutations and MET wild-type (66.7% versus 14.3%, p = 0.103; 66.7% versus 29.9%, p = 0.075, respectively). We found that patients with MET-non-ex14 mutations had a numerically longer progression free survival (PFS) than those with METex14 mutations and MET wild-type (p = 0.169). Moreover, the PFS was significantly longer in MET-non-ex14-mutant subgroup than patients with METex14 mutations (median PFS, 9.1 versus 2.1 months, p = 0.025). Correspondingly, the overall survival (OS) was significantly longer in MET-non-ex14-mutant subgroup than their wild-type counterparts (median OS, not reached versus 11 months, p = 0.039). Additionally, patients with MET-non-ex14 mutations exhibited relatively better OS versus METex14-mutant patients (median OS, not reached versus 18 months, p = 0.175). Conclusions: MET-non-ex14 mutations were associated with higher TMB, improved DCB rate, and could act as a favorable prognostic biomarker in ICIs-treated NSCLC patients.


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