We analyzed the number of circulating tumor cells (CTCs) and Epstein–Barr virus DNA (EBV DNA) for diagnosis, monitoring and prognosis of patients with metastatic nasopharyngeal carcinoma (mNPC). The ...levels of CTCs and EBV DNA were measured at baseline and after first‐line chemotherapy in 148 mNPC patients prospectively enrolled between December 2014 and August 2016. We also collected 122 non‐mNPC cases within the same time frame for examining CTCs and EBV DNA at baseline. In 270 NPC patients, we observed improved specificity (86.0% vs. 41.0%) and inferior sensitivity (42.3% vs. 81.3%) of CTCs as compared to EBV DNA for diagnosis of distant metastasis. mNPC patients were stratified into unfavorable and favorable prognostic groups, respectively, based on CTC of 12 at baseline and 1 after first‐line chemotherapy and EBV DNA of 10,000 at baseline and 4,000 after first‐line chemotherapy. Conversion of baseline unfavorable CTCs and EBV DNA to favorable after first‐line chemotherapy was associated with significantly longer progression‐free survival (PFS) and overall survival (OS) compared to patients with unfavorable CTCs and EBV DNA at both time points. Among patients with a complete/partial response as per imaging evaluation, favorable CTCs and EBV DNA levels after first‐line chemotherapy were associated with significantly longer PFS and OS. In conclusion, our data demonstrated the number of CTCs and EBV DNA before, after and during first‐line chemotherapy were strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
What's new?
Endemic nasopharyngeal carcinoma (NPC) is associated with latent infection of the oncogenic Epstein‐Barr virus (EBV) and frequently metastasizes to distant lymph nodes and organs. Metastatic NPC is treated by serial administration of cytotoxic or targeted therapies and treatment response is generally assessed with serial imaging, which often fails to detect changes in tumor burden. Here, the authors show that the number of circulating tumor cells (CTCs) and EBV DNA levels before, after, and during first‐line chemotherapy are strong predictive markers for mNPC patients. When utilized in conjunction with imaging studies, CTCs and EBV DNA could provide additional prognostic information.
Objectives
Nasopharyngeal carcinoma (NPC) patients with retropharyngeal lymph node (RPLN) recurrence typically undergo reirradiation and experience severe radiotoxicity. Salvage open surgery is ...challenging because gaining access to the retropharyngeal space is complex and risky. Thus, only several centers can perform this procedure, and complications are common. We applied transoral robotic surgery RPLN dissection (TORS‐RPLND) to NPC patients with RPLN recurrence to address the problem with open surgery.
Materials and Methods
From March 2017 to October 2020, 10 NPC patients with RPLN recurrence underwent TORS‐RPLND using the da Vinci Si/Xi Surgical System. We applied the balloon occlusion test to protect the internal carotid artery, induction chemotherapy to shrink large tumors preoperatively, and ultrasound positioning to effectively locate unrecognizable RPLNs during surgery. Clinical characteristics, complications, and survival outcome data were retrospectively collected.
Results
Of 10 patients, 8 underwent en bloc resection via TORS‐RPLND, and the remaining 2 patients were converted to open surgery because we failed to identify the RPLN during TORS. After introducing intraoperative ultrasound positioning, no such failure occurred. The mean operative time and intraoperative blood loss were 297 ± 120 min and 40 ± 43 ml, respectively. All surgical margins were negative. TORS‐related complications were mild, and the most severe one was grade 3 dysphagia in one patient who underwent conversion to open surgery (10%). With a median follow‐up of 19 months, only 1 (10%) patient developed cervical recurrence.
Conclusions
TORS‐RPLND is feasible, safe, and effective in the treatment of NPC patients with RPLN recurrence, especially with the help of intraoperative ultrasound positioning.
Level of Evidence
4 Laryngoscope, 131:E1895–E1902, 2021
To compare intensity‐modulated radiotherapy (IMRT) with cisplatin (CDDP) versus cetuximab (CTX) and nimotuzumab (NTZ) for Stage II‐IVb Nasopharyngeal Carcinoma (NPC). A total of 1,837 patients with ...stage II–IVb NPC who received IMRT plus CTX or NTZ, or CDDP between January 2009 and December 2013 were included in the current analysis. Using propensity scores to adjust for potential prognostic factors, a well‐balanced cohort of 715 patients was created by matching each patient who underwent IMRT plus concomitant NTZ/CTX with four patients who underwent IMRT plus concomitant CDDP (1:4). Efficacy and safety were compared between the CTX/NTZ and CDDP groups of this well‐balanced cohort. Furthermore, we conducted multivariate analysis and subgroup analysis based on all the 1,837 eligible cases. There was no significant difference between CTX/NTZ group and CDDP group in terms of DFS (3‐year, 86.7% vs. 86.2%, p > 0.05), LRRFS (96.2% vs. 96.3%, p > 0.05), DMFS (91.1% vs. 92.3%, p > 0.05) and OS (91.7% vs. 91.9%, p > 0.05). Subgroup analysis demonstrated a significant interaction effect between patients with IMRT plus CTX/NTZ and N3 node stage on LRRFS with the highest risk of loco‐regional relapse (HR 8.85, p = 0.001). Significantly increased hematologic toxicities, gastrointestinal reactions were observed in the CDDP group (p < 0.05). Patients of 3.4–4.7% experienced severe hematologic toxicities during the treatment with concomitant CTX and NTZ. Increased rate of CTX related‐skin reaction and mucositis was observed in the CTX group. CTX/NTZ used concurrently with IMRT may be comparable to those of the standard CDDP‐IMRT combination for maximizing survival for patients with stage II‐IVb NPC.
What's new?
Standard treatment for nasopharyngeal carcinoma (NPC) that has spread to lymph nodes in the head and neck entails concurrent cisplatin (CDDP) and intensity‐modulated radiotherapy (IMRT). High toxicity rates, however, limit the utility of this approach. The present study examines an alternative strategy: cetuximab (CTX) and nimotuzumab (NTZ) plus IMRT. No differences in risk of disease progression, relapse, metastasis or death were observed in a direct comparison between CDDP plus IMRT and CTX/NTZ plus IMRT in NPC patients. Both regimens were associated with hematologic toxicities and with toxicities targeting different tissues, warranting further investigation of side effects specific to CTX/NTZ.
It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 ...matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8
T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.
Objective
To compare survival effects of comprehensive neck dissection (CND) and selective neck dissection (SND) for patients with nasopharyngeal carcinoma (NPC) with only regional failure.
Methods
A ...total of 294 recurrent T0N1‐3M0 NPC patients who underwent neck dissection in Sun Yat‐Sen University Cancer Center, Guangzhou, People's Republic of China, between January 1984 and February 2014, were enrolled in the survival and interaction analyses. Using propensity scores to adjust for potential prognostic factors, an additional well‐balanced cohort of 210 patients was constructed by matching each patient who received SND with one patient who underwent CND (1:1); the differences were then compared between SND and CND in terms of overall survival (OS), local recurrence‐free survival (LRFS), regional recurrence‐free survival (RRFS), and distant metastasis‐free survival (DMFS).
Results
Both univariate and multivariate analyses showed that SND was not inferior to CND (P > 0.05) but demonstrated that extracapsular spread (ECS) (hazard ratio HR 3.49, 95% confidence interval CI 2.30–5.29, P < 0.001), recurrent N stage (rN stage) (HR 1.96, 95% CI 1.29–2.97, P = 0.002), and positive margins (HR 3.67, 95% CI 2.40–5.62, P < 0.001) were independent poor prognostic factors for OS. The interaction effects between the dissection style and each independent factor were not significant for OS, LRFS, RRFS, or DMFS (P > 0.05). Furthermore, no survival differences were found between SND and CND in the case‐matched cohort in terms of OS, LRFS, RRFS, or DMFS (P = 0.550, 0.930, 0.214, and 0.146, respectively).
Conclusion
With a similar radical dissection extent around the tumor rather than dissection of extensive lymph region distal to the lesion, SND is not inferior to CND for patients with NPC with only cervical failure. ECS, rN stage, and positive margins were adverse independent prognostic factors for patients with NPC.
Level of Evidence
4 Laryngoscope, 129:387–395, 2019
We used randomized trials of radiotherapy (RT) with or without chemotherapy in non-metastatic nasopharyngeal carcinoma to investigate the survival benefit of chemoradiotherapy regimens between ...two/three-dimensional radiotherapy (2D/3D RT) and intensity-modulated radiotherapy (IMRT).
Overall, 27 trials and 7,940 patients were included. Treatments were grouped into seven categories including RT alone, induction chemotherapy (IC) followed by RT (IC-RT), RT followed by adjuvant chemotherapy (RT-AC), IC followed by RT followed by AC (IC-RT-AC), concurrent chemo-radiotherapy (CRT), IC followed by CRT (IC-CRT), and CRT followed by AC (CRT-AC). To distinguish between 2D/3D RT and IMRT, three categories in IMRT were newly added, including CRT in IMRT, IC-CRT in IMRT, and CRT-AC in IMRT. The P score was used to rank the treatments.
Both fixed- and random-effects frequentist and Bayesian network meta-analysis models were applied, which provided similar results and the same ranking. IC-CRT was the most effective regimen compared with CRT-AC and CRT in the IMRT era for overall survival (OS) (HR, 95% CI, IC-CRT vs. CRT-AC, 0.61 (0.45, 0.82); IC-CRT vs. CRT 0.65 (0.47, 0.91)), progression-free survival (PFS) (0.69 (0.54, 0.88); 0.63 (0.49, 0.80)), and distant metastasis-free survival (DMFS) (0.58 (0.28, 1.21); 0.60 (0.42, 0.85)). CRT-AC achieved the highest survival benefit compared with CRT, and IC-CRT for loco-regional relapse-free survival (LRRFS) (0.44 (0.15, 1.28); 0.72 (0.22, 2.33)). Among these 10 categories, after distinguishing between 2D/3D RT and IMRT, IC-CRT in IMRT ranked first for OS, PFS, and DMFS, and CRT-AC in IMRT ranked first for LRRFS.
IC-CRT should be the most suitable regimen for loco-regionally advanced NPC in the IMRT era.
Recent studies have shown that ovarian aging is strongly associated with the risk of breast cancer, however, its prognostic impact on breast cancer is not yet fully understood. In this study, we ...performed a multicohort genetic analysis to explore its prognostic value and biological features in breast cancer.
The gene expression and clinicopathological data of 3366 patients from the The Cancer Genome Atlas (TCGA) cohort, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) cohort and the GSE86166 cohort were analyzed. A total of 290 ovarian aging-related genes (OARGs) were included in the establishment of the prognostic model. Furthermore, functional mechanisms analysis, drug sensitivity, and immune cell infiltration were investigated using bioinformatic methods.
An eight OARG-based signature was established and validated using independent cohorts. Two risk subgroups of patients with distinct survival outcomes were identified by the OARG-based signature. A nomogram with good predictive performance was developed by integrating the OARG risk score with clinicopathological factors. Moreover, the OARG-based signature was correlated with DNA damage repair, immune cell signaling pathways, and immunomodulatory functions. The patients in the low-risk subgroup were found to be sensitive to traditional chemotherapeutic, endocrine, and targeted agents (doxorubicin, tamoxifen, lapatinib, etc.) and some novel targeted drugs (sunitinib, pazopanib, etc.). Moreover, patients in the low-risk subgroup may be more susceptible to immune escape and therefore respond less effectively to immunotherapy.
In this study, we proposed a comprehensive analytical method for breast cancer assessment based on OARG expression patterns, which could precisely predict clinical outcomes and drug sensitivity of breast cancer patients.
Background
Postradiation nasopharyngeal necrosis (PRNN) is a severe complication after radiotherapy in patients with nasopharyngeal carcinoma (NPC), which can severely affect the quality of life and ...threaten the patient's life. Only 13.4%–28.6% of patients can be cured by traditional repeated endoscopic debridement. Here, we introduced an innovative curative‐intent endoscopic surgery for PRNN patients and evaluated its clinical efficacy.
Methods
Clinical data of 72 PRNN patients who underwent radical endoscopic necrectomy, followed by reconstruction using a posterior pedicle nasal septum and floor mucoperiosteum flap were analyzed to determine the efficacy of this surgery. The endpoints were complete re‐epithelialization of the nasopharyngeal defect, relief of headache, and overall survival (OS).
Results
All surgeries were successfully performed without any severe postoperative complications or death. The median value of numeric rating scales of pain decreased from 8 before surgery to 0 after surgery (P < 0.001). Fifty‐one patients (70.8%) achieved complete re‐epithelialization of the nasopharyngeal defect. The number of cycles of radiotherapy (odds ratio OR, 7.254; 95% confidence interval CI 1.035–50.821; P = 0.046), postoperative pathological result (OR, 34.087; 95% CI 3.168–366.746; P = 0.004), and survival status of flap (OR, 261.179; 95% CI 17.176–3971.599; P < 0.001) were independent risk factors of re‐epithelialization of the nasopharyngeal defects. Postoperative pathological result (hazard ratio HR, 5.018; 95% CI 1.970–12.782; P = 0.001) was an independent prognostic factor for OS. The 2‐year OS rate of the entire cohort was 77.9%.
Conclusion
Curative‐intent endoscopic necrectomy followed by construction using the posterior pedicle nasal septum and floor mucoperiosteum flap is a novel, safe, and effective treatment of PRNN in patients with NPC.
The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear.
To investigate the efficacy and safety of locoregional radiotherapy in de novo ...mNPC.
Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months.
The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy.
The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety.
Overall, 126 patients were enrolled (105 men 83.3% and 21 women 16.7%; median IQR age, 46 39-52 years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio HR, 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group.
In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC.
ClinicalTrials.gov Identifier: NCT02111460.
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