Residual Nasopharyngeal Carcinoma Research Articles

Toripalimab plus capecitabine in the treatment of patients with residual nasopharyngeal carcinoma: a single-arm phase 2 trial

Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

The Role of Circulating Tumor Cells in the Prognosis of Local Recurrence and Local Residual Nasopharyngeal Carcinoma Undergoing Endoscopic Resection.

Purpose To investigate the role of circulating tumor cells in the prognosis of local recurrence and local residual nasopharyngeal carcinoma undergoing endoscopic surgery. Methods A total of 56 patients with locally residual nasopharyngeal carcinoma (NPC) who underwent nasal endoscopic surgery from August 2018 to December 2021 were included. The status of circulating tumor cells (CTC) before and after surgery was detected, and its relationship with clinical characteristics and postoperative survival was analyzed. Results After nasal endoscopy, the positive rates of CTC and mesenchymal CTC (MCTC) detected in patients with nasopharyngeal carcinoma were significantly lower than those before treatment (P=0.0376; P=0.0212). Before nasal endoscopy, the status of CTC and MCTC was significantly correlated with the T stage (P < 0.05). After nasal endoscopy, the status of CTC and MCTC was significantly correlated with the TNM stage, T stage, and first radiotherapy mode (P < 0.05). The PFS of patients with different clinical characteristics was analyzed, and the results showed that the PFS of NPC patients with CTC (+) was significantly shorter than that of CTC (−) patients (18.71 vs. 22.47, P < 0.05) and the PFS of NPC patients with MCTC (+) was significantly shorter than that of MCTC (−) patients (18.22 vs. 22.30, P < 0.05). The PFS of NPC patients in TNM stage (I-II) was significantly longer than that in TNM stage (III) patients (22.53 vs. 18.57, P < 0.05). The PFS of NPC patients whose first radiotherapy mode was conventional was significantly longer than that of patients whose first radiotherapy mode was enhanced (22.14 vs. 16.85, P < 0.05). The COX analysis showed that MCTC and TNM stages were independent risk factors affecting the prognosis of local recurrence or local residual nasopharyngeal carcinoma after endoscopic resection (P < 0.05). Conclusion The detection of CTC is helpful for the prognosis evaluation of local recurrence or local residual NPC after endoscopic resection of NPC. The MCTC is an important factor affecting the prognosis of NPC patients.

The Dual-Targeted Peptide Conjugated Probe for Depicting Residual Nasopharyngeal Carcinoma and Guiding Surgery.

Detecting residual nasopharyngeal carcinoma (rNPC) can be difficult because of the coexistence of occult tumours and post-chemoradiation changes, which poses a challenge for both radiologists and surgeons using current imaging methods. Currently, molecular imaging that precisely targets and visualises particular biomarkers in tumours may exceed the specificity and sensitivity of traditional imaging techniques, providing the potential to distinguish tumours from non-neoplastic lesions. Here, we synthesised a HER2/SR-BI-targeted tracer to efficiently position NPC and guide surgery in living mice. This bispecific tracer contained the following two parts: IRDye 800 CW, as an imaging reagent for both optical and optoacoustic imaging, and a fusion peptide (FY-35), as the targeting reagent. Both in vitro and in vivo tests demonstrated that the tracer had higher accumulation and longer retention (up to 48 h) in tumours than a single-targeted probe, and realised sensitive detection of tumours with a minimum size of 3.9 mm. By visualising the vascular network via a customised handheld optoacoustic scan, our intraoperative fluorescence molecular imaging system provides accurate guidance for intraoperative tumour resection. Integrating the advantages of both optical and optoacoustic scanning in an intraoperative image-guided system, this method holds promise for depicting rNPC and guiding salvage surgery.

Failure Patterns of Recurrence and Metastasis After Intensity-Modulated Radiotherapy in Patients With Nasopharyngeal Carcinoma: Results of a Multicentric Clinical Study.

PurposeThis study aimed to explore factors associated with recurrence and metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) and provide evidence for NPC treatment.MethodsWe retrospectively analysed the treatment dose and survival outcomes of 645 patients with nasopharyngeal carcinoma without distant metastases treated with IMRT for the first time at three treatment centres in the Guangxi Zhuang Autonomous Region, China, between January 2009 and December 2012.ResultsThere were 9.3% of patients (60/645) had recurrence and 17.5% (113/645) had distant metastasis 5 years after treatment. The 1-year, 3-year and 5-year local recurrence rates were 0.9%, 6.5% and 9.0% respectively. And the 1-year, 3-year and 5-year distant metastasis rates were 3.4%, 10% and 17.2%, respectively. In the 60 patients with recurrence, the in-field, marginal-field, and out-field recurrence rates were 93.3% (56/60), 5.0% (3/60) and 1.7% (1/60), respectively. Recurrence failures occurring within the first three years after treatment accounted for 81.7% (49/60). In the 113 patients with metastasis, the size of the cervical lymph node, the presence of lower cervical lymph node metastasis, the residual cervical lymph node size and the time of residual cervical lymph node complete response (CR) were independent prognostic factors for DMFS (P <0.05).ConclusionMost recurrences occured in the first three years after IMRT. In-field recurrence was the most common pattern for loco-regional failure of NPC treatment. The risk of distant metastasis was positively correlated with higher N stage, lower neck nodal metastasis, larger size of cervical lymph nodes, and longer time to response for residual NPC in cervical adenopathy.

Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be a phantom tumor phenomenon.

Some nasopharyngeal carcinoma (NPC) patients may present convincing radiological evidence mimicking residual or recurrent tumor after radiotherapy. However, by means of biopsies and long term follow-up, the radiologically diagnosed residuals/recurrences are not always what they appear to be. We report our experience on this “phantom tumor” phenomenon. This may help to avoid the unnecessary and devastating re-irradiation subsequent to the incorrect diagnosis.In this longitudinal cohort study, we collected 19 patients of image-based diagnosis of residual/recurrent NPC during the period from Feb, 2010 to Nov. 2016, and then observed them until June, 2019. They were subsequently confirmed to have no residual/recurrent lesions by histological or clinical measures. Image findings and pathological features were analyzed.Six patients showed residual tumors after completion of radiotherapy and 13 were radiologically diagnosed to have recurrences based on magnetic resonance imaging (MRI) criteria 6 to 206 months after radiotherapy. There were 3 types of image patterns: extensive recurrent skull base lesions (10/19); a persistent or residual primary lesion (3/19); lesions both in the nasopharynx and skull base (6/19). Fourteen patients had biopsy of the lesions. The histological diagnoses included necrosis/ inflammation in 10 (52.7%), granulation tissue with inflammation in 2, and reactive epithelial cell in 1. Five patients had no pathological proof and were judged to have no real recurrence/residual tumor based on the absence of detectable plasma EB virus DNA and subjective judgment. These 5 patients have remained well after an interval of 38–121 months without anti-cancer treatments.Image-based diagnosis of residual or recurrent nasopharyngeal carcinoma may be unreliable. False positivity, the “phantom tumor phenomenon”, is not uncommon in post-radiotherapy MRI. This is particularly true if the images show extensive skull base involvement at 5 years or more after completion of radiotherapy. MRI findings compatible with NPC features must be treated as a real threat until proved otherwise. However, the balance between under- and over-diagnosis must be carefully sought. Without a pathological confirmation, the diagnosis of residual or recurrent NPC must be made taking into account physical examination results, endoscopic findings and Epstein-Barr virus viral load. A subjective medical judgment is needed based on clinical and laboratory data and the unique anatomic complexities of the nasopharynx.

Comparing endoscopic surgeries with open surgeries in terms of effectiveness and safety in salvaging residual or recurrent nasopharyngeal cancer: Systematic review and meta‐analysis

Consensus has yet to be reached on the optimal operation for patients with residual or recurrent nasopharyngeal carcinoma (NPC). To compare effectiveness and safety of open surgery and endoscopic surgery for patients with residual or recurrent NPC. Pubmed, Embase, and Cochrane were searched for relevant publications from January 1, 2000 to May 1, 2017. Included studies reported specific residual or local recurrent nasopharyngeal cancer survival data. Proportional meta-analysis was performed on both outcomes with a random-effects model, and the 95% confidential intervals were calculated by Stata 12.0 software. For patients with different tumor classification, a downward trend of 2-year overall survival (OS) was observed for both surgical populations. Endoscopic surgeries achieved bigger rates than open surgeries in patients with recurrent tumor (rT) 1, rT2, and rT3 (93% vs 87%, 77% vs 63%, 67% vs 53%). As for patients with rT4, 2-year OS was similar (35% vs 35%).In addition, the former is less severe complications, lower local recurrence rates (27% vs 32%). Our study found that, compared to open surgery, endoscopic surgery was a safer and more effective treatment modality in managing patients with recurrent or residual NPC.

Preliminary exploration of 3D printed individualized applicator for 3D-image-guided intracavitary HDR-brachytherapy for nasopharyngeal carcinoma

Objective To explore the feasibility of 3D printed individualized applicator for the intracavitary HDR-brachytherapy for nasopharyngeal carcinoma. Methods CT scan was performed in 1 case of recurrent rT1 nasopharyngeal carcinoma and 1 case of T2 residual nasopharyngeal carcinoma and the obtained images were transmitted to 3D image processing software. The geometric contour parameters of the nasopharyngeal cavity were obtained and a pipeline was designed to make it close to the recurrent gross tumor volume (rGTV). Individualized cavity applicators were created by using 3D printer. The applicator was inserted into the patient′s nasopharyngeal cavity through oral cavity. The source tube and false source were inserted into the preset pipe of the applicator. CT scan was performed again and the images were transmitted to the 3D brachytherapy planning system. After delineating the target volume and organ at risk, treatment plan was optimized. After completing the first treatment, the applicator was removed. Before second treatment in a few days, CT scan was reviewed to confirm whether the position was correct. Results When the applicator was inserted into the nasopharyngeal cavity, it could be fully aligned with the nasopharyngeal wall and self-fixed without additional fixation measures. Comparing the location of false source in multiple reviews of CT scan, the error was ≤1 mm. No significant discomfort was reported throughout the treatment. In optimized three-dimensional treatment, 100% prescription dose curve included the full rGTV, maximum dose of the brain stem and spinal cord was<30% prescription dose. Recurrent patients were given with a prescription dose of DT 40Gy/8 fractions/4 weeks and patients with residual tumors were given with 12Gy/2 fractions/1 week. No tumor recurrence was observed at postoperative 3 months in two cases. Conclusions The 3D printed individualized nasopharyngeal intracavitary applicator has the advantages of self-fixation, accurate location, good repeatability and good patient tolerance. The short-term outcome is effective, whereas its long-term clinical effect and adverse reactions need to be further observed. Key words: 3D printed; Individualized applicator; Nasopharyngeal neoplasm/intracavitary radiotherapy

Diffusion weighted magnetic resonance imaging of pre and post treatment nasopharyngeal carcinoma

ObjectivesTo evaluate the utility of different Apparent Diffusion Coefficient (ADC) values on Diffused Weighted Magnetic Resonance Imaging (DW-MRI) for nasopharyngeal carcinoma (NPC). Study design and settingA retrospective cohort study in a single tertiary medical center. Subjects and methodsThe study group consists of patients with pathology proven NPC that underwent DW-MRI prior or/and following a non-surgical chemo radiation treatment between the years 2007 and 2017. ADC thresholds were analyzed and compared for primary (pre-treatment) and expected post-irradiation NPC cases and healthy controls. ResultsWe recruited 144 patients who underwent 195 MRI's for NPC. 25 DW-MRI were performed before (primary, active NPC) and 56 following (no residual NPC) treatment. 45 out of 225 patients who had brain DW-MRI for other reasons (control group) had measurable nasopharynx tissue (N = 33, adjusted for age and gender). The mean ADC of NPC prior to treatment (0.69 ± 0.13 × 10−3 mm2/s) was significantly lower (ANOVA, P < 0.001) compared to the mean ADC of the adjusted controls (1.11 ± 0.25 × 10−3 mm2/s) and post-treatment (1.49 ± 0.28 × 10−3 mm2/s) groups. An ADC threshold of 0.805 × 10−3 mm2/s had 94% and 93.9% sensitivity and specificity rates, respectively and an odds ratio of 175[95%CI(23.25–1000)], comparing ADC levels of pre-treatment NPC patients and adjusted control group. An ADC threshold of 0.965 × 10−3 mm2/s yielded 100% positive and negative predicted values distinguishing pre-treatment and post-treatment NPC patients (free of disease). There was no statistical association between ADC levels and tumor volume/stage, nodal stage or group staging. ConclusionsADC levels have distinct values in newly diagnosed and follow up of NPC.

POST-TREATMENT FOLLOW-UP OF NASOPHARYNGEAL CARCINOMA PATIENTS: A REVIEW

Introduction&#x0D; Locoregional failure of nasopharyngeal carcinoma (NPC) occurs despite the aggressive treatment that has been done. Optimal and accurate follow-up schedule after the radiotherapy or chemoradiotherapy sessions could improve the patient's quality of life (QoL).&#x0D; Discussion&#x0D; Kwong et al. reported complete histological remission within 3 months after therapy and positive histological signs at &gt;12 weeks considered a persistent disease. Kong et al. (2017) showed that the pathological treatment response using CT scan and MRI and stated that the median time to full regressions is 4.9 months. Some studies also reported that primary tumor continuously regressed &gt;4 months after treatment and delayed remission &gt;12 weeks is not a prognostic factor for poor survival.&#x0D; The use of MRI is superior to CT scan to detect residual or recurrent NPC. MRI showed good results in differentiating mature scar and tumor, whereas CT scan could not differentiate fibrosis and tumor because of the radiation therapy-induced inflammation. On the other hand, PET-CT has higher sensitivity compared to CT scan and MRI, but poor cost-effectiveness. Various studies and NCCN 2018 guidelines recommend the use of imaging between the third and sixth months after therapy to evaluate treatment response. &#x0D; Conclusion&#x0D; Assessment of treatment-related late toxicities also an important factor to improve patient’s QoL. Evaluation of nutrition, speech difficulties, swallowing, hearing, dental care should be done annually and peer support groups can help improve patient’s QoL.&#x0D; Assessment of residual disease should be done at the minimum of 10 weeks after the completion of the therapy and long-term follow-up is a must because locoregional recurrences of NPC are common within the first two to three years after the treatment.

Failure Patterns of Distant Metastasis after Intensity-Modulated Radiation Therapy in Patients with Nasopharyngeal Carcinoma

This study aimed to explore factors associated with distant metastasis after intensity-modulated radiotherapy (IMRT) in patients with nasopharyngeal carcinoma (NPC), and to provide evidence that could be used to design new treatment strategies for NPC. We performed a retrospective analysis of 645 patients with NPC at three treatment centers in China, from January 2009 to December 2011. All patients had untreated, non-metastatic NPC prior to receiving IMRT. The Kaplan-Meier method was used to calculate patient survival rates, and log-rank testing was used to compare survival differences. Univariate analysis and Cox proportional hazard analysis were performed to explore treatment failure patterns and risk factors for distant metastasis after radiotherapy. Of the 645 patients, 17.5% (113/645) had distant metastasis 5 years after treatment. The median metastatic age was 47 years (range: 20-74 years), and the median metastatic time was 24 months after IMRT (range: 6-79 months). The 5-year overall survival rate (OS) was 84.2% and the 5-year recurrence-free survival (RFS) rate was 90.1%. The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) rates were 96.6%, 87.4%, and 82.8%, respectively. Univariate and multivariate analysis showed that N staging, the size of the cervical lymph node, the presence of lower cervical lymph node metastasis, residual cervical lymph nodes at the end of radiotherapy, the residual cervical lymph node lesion size, and the time of cervical lymph node lesion complete remission were independent prognostic factors for DMFS (p<0.05). Radiotherapy combined with chemotherapy can reduce the incidence of distant metastasis after IMRT. The risk of distant metastasis after IMRT was positively correlated with N staging, lower cervical lymph node metastasis, the size of the cervical lymph nodes, residual NPC in cervical lymph nodes at the end of radiotherapy, and the residual cervical lymph node lesion size. Persistent residual cervical lymph node lesions three months after IMRT was a risk factor for poor prognosis, therefore more effective interventions should be explored.

Clinical outcomes of residualorrecurrent nasopharyngeal carcinoma treated with endoscopic nasopharyngectomy plus chemoradiotherapy or with chemoradiotherapy alone: a retrospective study.

BackgroundLocal residual and recurrent nasopharyngeal carcinoma (NPC) generally shows treatment failure after standard radiotherapy with or without concurrent chemotherapy. Whether endoscopic nasopharyngectomy might provide an additional therapeutic advantage remains controversial. Therefore, we retrospectively compared the clinical prognoses of patients with residual or recurrent NPC treated with endoscopic nasopharyngectomy combined with chemoradiotherapy (CRT) with those of patients treated with CRT alone.Methods and MaterialsA total of sixty-two patients with local residual or recurrent NPC were studied retrospectively: 36 patients received endoscopic nasopharyngectomy combined with CRT, whereas 26 patients who refused the surgery or had surgical contraindications received CRT alone. Serum Epstein-Barr virus (EBV) DNA levels were measured pre- and post-treatment. The differences in prognosis between the two treatment regimens and the pre- and post-treatment changes in EBV-DNA levels were analyzed.ResultsThe median follow-up time was 31 months, with a 3-year overall survival (OS) of 51.40% and a 3-year disease-free survival (DFS) of 46.86%. The surgery + CRT group had a better OS than the CRT alone group did (χ2 = 4.054, P = 0.044). The pretreatment EBV-DNA levels showed a positive correlation with the clinical staging of recurrent NPC (χ2 = 11.674, P = 0.009). Patients with negative pretreatment serum EBV-DNA levels showed a superior OS to those of patients who tested positive for EBV-DNA (>0 copy/mL) (χ2 = 9.833, P = 0.002). The post-treatment EBV-DNA levels, compared with the pretreatment levels, decreased significantly in the surgery + CRT group (Z = − 3.484, P = 0.000). In contrast, the EBV-DNA levels after CRT alone did not decrease significantly (Z = − 1.956, P = 0.051). Multivariate analysis indicated that local staging, pretreatment EBV-DNA load, and the treatment method were independent risk factors for OS. Subgroup analysis indicated that the patients who tested negative for EBV-DNA before the treatment and those who received surgery + CRT showed a better OS than those who received CRT alone.ConclusionsThe pretreatment serum EBV-DNA level was associated with disease prognosis. The combination therapy preceded by surgery can effectively decrease the copy number of EBV-DNA. Patients with local intermediate- and late-stage NPC, especially those negative for EBV-DNA, may consider opting for surgery followed by post-operative adjuvant radiotherapy or chemotherapy.

Salvage endoscopic nasopharyngectomy for local recurrent or residual nasopharyngeal carcinoma: a 10-year experience

Our aim was to review the outcomes of endoscopic nasopharyngectomy performed on a large series of patients with residual or recurrent nasopharyngeal carcinomas and to identify the prognostic factors. Ninety-one patients with residual (10) and recurrent (81) nasopharyngeal carcinomas who underwent endoscopic nasopharyngectomy were enrolled in our study. Clinical information including gender, age, medical history, symptoms, radiographic findings, tumor stage, treatment, recurrence time, postoperative pathological examination, complications, and outcomes at last follow-up visit was collected. The survival curves and multivariate survival analysis were analyzed using the Kaplan-Meier and Cox proportional hazards model. Our study included 71 men and 20 women with a median age of 51years. The lesions were staged as follows: rT1, 30; rT2, 13; rT3, 29; and rT4, 19. No serious operative or postoperative complication was observed. The median follow-up period was 23months (range, 4-109months). Tumor necrosis was identified in 40 of 91 patients. At the last follow-up, 42 patients were free of disease, 10 were alive with disease, and 39 had died. At 2- and 5-year follow-up, the overall survival rates were 64.8% and 38.3%, respectively; the disease-free survival rates were 57.5% and 30.2%, respectively, for the two periods. Multivariate analysis showed that T classification (P=0.02) and tumor necrosis (P=0.024) were independent risk factors. Endoscopic nasopharyngectomy is a feasible and effective surgical treatment for recurrent and residual nasopharyngeal carcinomas.

Clinical Study on Photodynamic Therapy (PDT) In Patients with Nasopharyngeal Carcinoma in Yogyakarta Review of Life Expectancy and Cytokine Level

Background: Nasopharyngeal carcinoma is a malignancy in nasopharynx cavity originated from mucosal epithelial cell of nasopharynx. In Indonesia, nasopharyngeal carcinoma is the most considerable malignancy in head and neck area with the highest mortality rate. Objective: To perceive that photodynamic therapy in nasopharyngeal carcinoma either residual or recurrence patients after receiving radiation or in chemo radiation therapy will yield a well-responded therapy, better life expectancy compared to those who didn't receive PDT, and inducing systemic anti-tumor response which was marked by the increased level of immune-response cytokines. Methods: This research took place in Department of Otorhinolaryngology Head and Neck Surgery Faculty of Medicine University of Gadjah Mada/Dr Sardjito General Hospital Yogyakarta, Indonesia using cohort retrospective design. The subjects of this research are patients with residual or recurrence nasopharyngeal carcinoma who had received photodynamic therapies between the years 2005-2011. Pre and posttest examination were used to test the hypothesis of the cytokines level difference before and after photodynamic therapies. Results: As much as 58.1% patients were men, and 41.9% of patients were female. Most of the patients were above 40 years of age. As much as 21 out of 31 patients (67.7%) were previously diagnosed as nasopharyngeal carcinomas in late stages, in this case the given treatment was chemo radiation. The 5 years life expectancy of residual or recurrence nasopharyngeal carcinoma is 60.7%. This number was preferable compared to the life expectancy of nasopharyngeal carcinoma patients who received standard therapy of either radiation or chemo radiation. Residual and recurrence nasopharyngeal carcinoma patients diagnosed between year 2009- 2013 without photodynamic therapy showed the 5 year overall survival rate as much as 22.9% with the median 23.6 months. There was a significant difference of life expectancy either clinically or statistically in patients with residual of recurrence nasopharyngeal cancer who received PDT compared to those who did not (p=0.004). Conclusion: In long-term observation, it was reported that photodynamic therapy (PDT) increased the 5 years survival rate in patients with residual or recurrence nasopharyngeal carcinoma. Patients who received PDT had life expectancy 5 years longer than patients who did not receive PDT.

Application of 18F-FDG PET-CT in nasopharyngeal carcinoma

18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) is the integration of functional imaging and anatomic information, which is found to be particularly valuable in TNM staging, tumor volume delineating, post-treatment assessment, identification of recurrent and residual nasopharyngeal carcinoma (NPC). The combination of 18F-FDG PET-CT with other image technologies, diffe-rent tracer agents, and specific molecular biomarkers can improve the application value of 18F-FDG PET-CT in NPC. Key words: Nasopharyngeal neoplasms; Radiotherapy; Fluorodeoxyglucose F18; Positron-emission tomography

Ionizing radiation promotes advanced malignant traits in nasopharyngeal carcinoma via activation of epithelial-mesenchymal transition and the cancer stem cell phenotype.

Post-irradiation residual mass and recurrence always suggest a worse prognosis for nasopharyngeal carcinoma (NPC). Our study aimed to investigate the malignant behaviors of post-irradiation residual NPC cells, to identify the potential underlying mechanisms and to search for appropriate bio-targets to overcome this malignancy. Two NPC cell lines were firstly exposed to 60 Gy irradiation, and residual cells were collected. In our previous study, colony formation assay detected the radioresistance of these cells. Here, the CCK-8 assay examined the cell sensitivity to paclitaxel and cisplatin. Wound-healing and Transwell assays were performed to investigate cell motility and invasion capabilities. Inverted phase-contrast microscopy was used to observe and photograph the morphology of cells. Expression levels of epithelial-mesenchymal transition (EMT)-related proteins were detected by western blot assay in NPC cells and tissues. The mRNA levels of cancer stem cell (CSC)-related genes were detected via qRT-PCR. The results revealed that residual NPC cells exhibited enhanced radioresistance and cross-resistance to paclitaxel and cisplatin. Higher capacities of invasion and migration were also observed. An elongated morphology with pseudopodia formation and broadening in the intercellular space was observed in the residual cells. Downregulation of E-cadherin and upregulation of vimentin were detected in the residual NPC cells and tissues. CSC-related Lgr5 and c-myc were significantly upregulated in the CNE-2-Rs and 6-10B-Rs radioresistance cells. Higher proportions of Lgr5+ cells were observed in radioresistant cells via immunofluorescent staining and flow cytometry. In conclusion, our study demonstrated that residual NPC cells had an advanced malignant transition and presented with both EMT and a CSC phenotype. This provides a possible clue and treatment strategy for advanced and residual NPC.

Analysis of clinical efficacy and the quality of life after endoscopic nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma

To explore the clinical efficacy of patients who underwent endoscopic salvage nasopharyngectomy for residual or recurrent nasopharyngeal carcinoma (rNPC) after irradiation failure, and examine the quality of life (QOL) of them who were at different tumor stage and given different postoperative treatment. Ninety-six patients who underwent endoscopic salvage nasopharyngectomy for rNPC between June 2009 and March 2015 were retrospectively reviewed. rTNM stage: 20 cases were at stage I, 16 at stage II, 44 at stage III, 16 at stage IV; rT1 22 cases (22.9%), rT2 16 cases (16.7%), rT3 42 cases (43.8%), rT4 16 cases (16.7%); rN0 92 cases (95.8%), rN1 2 cases (2.1%), rN2 2 cases (2.1%); No with distance metastasis. All the patients underwent endoscopic resection of lesions, and four cases with cervical metastasis received neck dissection at the same time.Postoperatively the self-reported, health-related QOL questionnaires were used to assess and compare the QOL of survival patients.SPSS 19.0 software was used to analyzed the data. The overall 1 year survival rates (SR), 2 year SR, 3 year SR were 83%, 68%, 63%, respectively. The median follow-up was 43 months. Cox regression analysis indicated the complete resection for rNPC and pathology were two independent factors affecting survival. The QOL of patients who received endoscopic salvage nasopharyngectomy only were better than the patients who received concurrent chemoradiation therapy or chemotherapy. The patients who underwent endoscopic salvage nasopharyngectomy for rNPC had a good survival rates and QOL.

Photodynamic therapy as salvage therapy for patients with nasopharyngeal carcinoma experiencing local failures following definitive radiotherapy

Treating local failures of nasopharyngeal carcinoma (NPC) is a challenge. This study evaluates photodynamic therapy (PDT) in the treatment of residual and recurrent NPC. In this phase II study, patients with local recurrent or residual NPC after curative intent (chemo-) radiation could be included. Exclusion criterion was a tumour depth more than 10mm. Foscan® 0.15mg/kg was administered intravenously. After 96h, the illumination was performed under local anaesthesia with a nasopharyngeal light applicator. Tumour response was measured 10 weeks after illumination by endoscopy, biopsy and CT-scan. Kaplan-Meier method was used for survival analysis. Twenty-one patients were included. Fourteen patients were treated for residual disease (67%), and two for recurrent (10%). For five patients this distinction could not be made, due to uncertainty about complete response after initial treatment. The median follow-up time was 32 months. Twenty patients (95%) had a complete response 10 weeks post-treatment. Two patients had recurrent local disease at 5 and 7 months post-PDT. They received another course of PDT, one with success. The 2-year local control rate was 75%, progression free survival was 49% and overall survival was 65%. Nine patients (43%) had no evidence of disease and were in a good clinical condition (ECOG Performance Scale 0) at the end of the study period. No serious adverse events were observed. This study showed that PDT is effective in treating local failures of NPC with a depth of less than 10mm. The treatment was easy to perform under local anaesthesia. Especially in regions were other modalities like radiation and surgery are limited PDT can be a good alternative treatment.

The effect of adjuvant chemotherapy on survival in patients with residual nasopharyngeal carcinoma after undergoing concurrent chemoradiotherapy.

BackgroundGuidelines from the U.S. National Comprehensive Cancer Network have recommended use of concurrent chemoradiotherapy (CCRT), followed by a 3-cycles combination of platinum and 5-fluorouracil chemotherapy as standard treatment for nasopharyngeal carcinoma (NPC). The benefits of CCRT for treatment of locally advanced NPC have been established. Whether platinum and 5-fluorouracil chemotherapy should be routinely added to locally advanced NPC after CCRT is still open to debate. Whether adjuvant chemotherapy provides an additional survival benefit for the subgroup of patients with residual nasopharyngeal carcinoma who have undergone CCRT is also unclear. This retrospective study was initiated to determine the survival benefit of adjuvant chemotherapy (AC) in residual NPC patients who have undergone concurrent chemoradiotherapy.MethodsThe retrospective study included 155 nasopharyngeal carcinoma patients who had local residual lesions after the platinum-based CCRT without or with AC. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), local relapse-free survival (LRFS) and distant metastasis-free survival (DMFS).ResultsMedian follow-up was 47 months. Adjuvant cisplatin or nedaplatin plus 5-fluorouracil chemotherapy did not significantly improve 3-year OS, LRFS, FFS, and DMFS for patients with residual nasopharyngeal carcinoma after undergoing CCRT. The 3-year OS rates for the no-AC group and AC group were 71.6% and 73.7%, respectively (P= 0.44). The 3-year FFS rates for no-AC group and AC group were 57.5% and 66.9%, respectively ((P= 0.19). The 3-year LRFS rates for no-AC group and AC group were 84.7% and 87.9%, respectively ((P= 0.51). The 3-year DMFS rates for no-AC group and AC group were 71.4% and 77.4%, respectively ((P= 0.23).ConclusionsSince we did not find sufficient data to support significant survival in 3-year OS, LRFS, FFS, and DMFS, whether Adjuvant cisplatin or nedaplatin and 5-fluorouracil chemotherapy should be routinely added to residual nasopharyngeal carcinoma patients after undergoing CCRT remain uncertain.

Endoscope-Guided Interstitial Intensity-Modulated Brachytherapy and Intracavitary Brachytherapy as Boost Radiation for Primary Early T Stage Nasopharyngeal Carcinoma

BackgroundIntracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC.Methodology/Principal FindingsTwo hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005–2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups.Conclusions/SignificanceIMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC.

Current treatment options for local residual nasopharyngeal carcinoma.

Opinion statementLocal residual disease occurs in 7-13 % after primary treatment for nasopharyngeal carcinoma (NPC). To prevent tumor progression and/or distant metastasis, treatment is indicated. Biopsy is the “gold standard” for diagnosing residual disease. Because late histological regression frequently is seen after primary treatment for NPC, biopsy should be performed when imaging or endoscopy is suspicious at 10 weeks. Different modalities can be used in the treatment of local residual disease. Interestingly, the treatment of residual disease has better outcomes than treatment of recurrent disease. For early-stage disease (rT1-2), treatment results and survival rates are very good and comparable to patients who had a complete response after the first treatment. Surgery (endoscopic or open), brachytherapy (interstitial or intracavitary), external or stereotactic beam radiotherapy, or photodynamic therapy all have very good and comparable response rates. Choice should depend on the extension of disease, feasibility of the treatment, and doctor’s and patient’s preferences and experience, as well as the risks of the adverse events. For the more extended tumors, choice of treatment is more difficult, because complete response rates are poorer and severe side effects are not uncommon. The results of external beam reirradiation and stereotactic radiotherapy are better than brachytherapy for T3-4 tumors. Photodynamic therapy resulted in good palliative responses in a few patients with extensive disease. Also, chemotherapeutics or the Epstein-Barr virus targeted therapies can be used when curative intent treatment is not feasible anymore. However, their advantage in isolated local failure has not been well described yet. Because residual disease often is a problem in countries with a high incidence of NPC and limited radiotherapeutic and surgical facilities, it should be understood that most of the above mentioned therapeutic modalities (radiotherapy and surgery) will not be readily available. More research with controlled, randomized trials are needed to find realistic treatment options for residual disease.