Locally Advanced Nasopharyngeal Carcinoma Research Articles

1125P - Prophylactic versus reactive nutritional supplement in local advanced nasopharyngeal carcinoma patients receiving radical chemo-radiotherapy

1125P - Prophylactic versus reactive nutritional supplement in local advanced nasopharyngeal carcinoma patients receiving radical chemo-radiotherapy

Magnetic Resonance Imaging Volumetry of Primary Nasopharyngeal Cancer in Patients Treated with Induction Gemcitabine and Cisplatin Followed by Concurrent Cisplatin and Volumetric Modulated Arc Therapy.

IntroductionThe addition of induction chemotherapy (IC) to the standard concurrent chemoradiotherapy (CCRT) is under consideration in locally advanced nasopharyngeal carcinoma (LANPC). To-date, no studies have reported primary gross tumour volume (GTVp) changes using gemcitabine and cisplatin as the IC phase in LANPC. We investigated the timing and magnitude of GTVp response throughout sequential gemcitabine and cisplatin IC and CCRT for LANPC. Toxicity and tumour control probability (TCP) analyses are also presentedMethodsTen patients with LANPC underwent sequential IC and CCRT between 2011 and 2015. All patients had magnetic resonance imaging (MRI) at three time points: before IC (MRI0), after IC (MRI1), and three months after CCRT (MRI3). Five of the 10 patients had an additional MRI four to five weeks into CCRT (MRI2). GTVp contours were delineated retrospectively using contrast-enhanced MRIs, and each GTVp underwent secondary review by a neuroradiologist. Acute toxicities were graded retrospectively via chart review based on the National Cancer Institute Common Terminology for Adverse Events version 4.0 (NCI CTCAE v4.0).ResultsMean GTVp reduction between MRI0 - MRI1 was from 68 cc to 47 cc and from 47 cc to 9 cc between MRI1 - MRI3. In patients with MRI2, the mean GTVp reduction between MRI1 - MRI2 was from 57 cc to 32 cc. Tumour control probability estimates increased by 0.11 after IC. Patients tolerated the treatment well with one Grade IV toxicity event.ConclusionThe observed GTVp response and improved tumor control probability support further investigation into the use of IC in LANPC.

Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy followed by adjuvant chemotherapy in locally advanced nasopharyngeal carcinoma

BackgroundConcurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) is currently recommended as the standard treatment for locally advanced nasopharyngeal carcinoma (LA-NPC). Neoadjuvant chemotherapy followed by concurrent chemoradiotherapy (NAC-CCRT) is an alternative strategy for decreasing tumor size and controlling micrometastases before main treatment. The aim of this study was to investigate and compare survival outcomes between LA-NPC patients treated with CCRT-AC and those treated with NAC-CCRT.MethodsThis retrospective cohort study included consecutive histologically confirmed LA-NPC patients that were treated with NAC-CCRT or CCRT-AC at Siriraj Hospital during the March 2010 to October 2014 study period. CCRT in both protocols consisted of 3-week cycles of cisplatin 100 mg/m2 with concurrent radiotherapy. Either NAC or AC consisted of 3-week cycles of cisplatin on day 1 and fluorouracil/leucovorin on days 1–4 for a maximum three cycles. The primary endpoint was 5-year overall survival (OS). Flexible parametric survival analysis was used, because the proportional hazards assumption of Cox regression was violated.ResultsOf the 266 LA-NPC patients that received treatment during the study period, 79 received NAC-CCRT and 187 received CCRT-AC. Median follow-up was 37 months. Significantly more patients with advanced clinical stage (stage IVA-IVB) received NAC-CCRT (86% in NAC-CCRT vs. 29% in CCRT-AC; p < 0.001). Compared to CCRT-AC in crude analysis, 3-year and 5-year OS of NAC-CCRT were 72% vs. 86% and 62% vs. 75% respectively (p = 0.059). Interestingly, the 3-year and 5-year post-estimation adjusted OS was 84% and 74% for NAC-CCRT and 81% and 70% for CCRT-AC, respectively (HR: 0.83, 95% confidence interval (CI): 0.45–1.56; p = 0.571). Also, adjusted analysis of distant-metastasis survival, NAC-CCRT showed HR was 0.79 (95% CI:0.37–1.72, p = 0.557). Conversely, adjusted analysis of locoregional relapse (LLR)-free survival revealed NAC-CCRT to have a significantly higher risk of LRR (HR: 2.18, 95% CI: 0.98–4.87; p = 0.057).ConclusionsThe results suggested that prognosis in the NAC-CCRT treated patients was not superior to that of the CCRT-AC treated individuals. In patients that receive neoadjuvant chemotherapy, locoregional relapse should be of concern. High-risk distant metastasis patients (N3 stage) that could achieve survival advantage from NAC-CCRT is an interesting and important topic for further study.

Induction chemotherapy for locally advanced nasopharyngeal carcinoma treated with concurrent chemoradiation: A systematic review and meta-analysis

PurposeTo determine if the addition of induction chemotherapy (IC) to concurrent chemoradiation (CCRT) in locally advanced nasopharyngeal carcinoma (LA-NPC) can improve survival. MethodsWe performed a meta-analysis of both randomized controlled trials (RCTs) and observational studies (OBS) to compare the effects of addition of IC to CCRT versus (vs) CCRT alone on overall survival (OS), progression free survival (PFS), distant metastasis-free survival (DMFS) and adverse events (AE) in LA-NPC. We searched MEDLINE for eligible studies comparing IC plus CCRT vs CCRT for LA-NPC from Jan 1996 to May 2017. We selected RCTs and OBS that included patients with non-metastatic, LA-NPC who received IC followed by CCRT or CCRT alone. Three reviewers independently assessed the abstracts for eligibility. We assessed the methodological quality of the included studies using the MERGE criteria. We performed the meta-analysis with random effects model. We used the GRADE approach to appraise the quality of evidence from RCTs. The primary outcome was OS; secondary outcomes included PFS, DMFS and AE. ResultsWe found six RCTs and five OBS including 2802 patients with low to moderate risk of bias in their methodological quality. There was high quality evidence from the RCTs that IC improved PFS (HR 0.69, 95% CI 0.57–0.84, P = 0.0003, I2 = 0%) and OS (HR 0.77, 95% CI 0.60–0.98, P = 0.03, I2 = 0%) significantly and was associated with more frequent AE. The estimates of IC effects from RCTs and OBS were similar (PFS HR 0.69 vs 0.71, interaction P (IP) = 0.92; OS HR 0.77 vs 0.58, IP = 0.27). ConclusionsIC delays disease progression and improves survival significantly for LA-NPC treated with CCRT, and was associated with more toxicity. There were no divergent results between RCTs and OBS. IC followed by CCRT can be considered one of the standard treatment options for LA-NPC.

Intensity-modulated radiotherapy plus nimotuzumab with or without concurrent chemotherapy for patients with locally advanced nasopharyngeal carcinoma.

ObjectiveThis study aimed to evaluate the safety and efficacy of intensity-modulated radiotherapy (IMRT) plus nimotuzumab with or without concurrent chemotherapy (CCT) for patients with locally advanced nasopharyngeal carcinoma (LA-NPC).Patients and methodsA total of 50 newly diagnosed patients with LA-NPC treated at the Affiliated Hospital of Jiangnan University between November 2011 and January 2017 were retrospectively analyzed. All patients received the combined treatment modality of nimotuzumab plus IMRT. Nimotuzumab was administered concurrently with IMRT at a weekly dose of 200 mg. Neoadjuvant, concurrent or adjuvant chemotherapy with the doublet regimen of taxanes (docetaxel or paclitaxel) plus platinum (cisplatin or nedaplatin) were administered. Among the 50 patients, 43 (86.0%) received ≥6 cycles of nimotuzumab (median 7 cycles, range 2–14 cycles) and 29 (58.0%) received two cycles of CCT with docetaxel plus nedaplatin.ResultsWith a median follow-up of 28.0 months, the 2-year progression-free survival (PFS) and overall survival were 83.29% (95% confidence interval [CI]: 67.93%–91.72%) and 97.67% (95% CI: 84.62%–99.67%), respectively. Both univariate and multivariate analyses revealed that cycles of nimotuzumab were significantly associated with PFS. Patients who received ≥6 cycles of nimotuzumab showed a better PFS than those receiving <6 cycles (P=0.006), whereas the addition of CCT failed to improve PFS. Oral mucositis was the most common adverse event, which was recorded as grade 3–4 in 18 (36.0%) patients. Besides, two (4.0%) patients experienced nimotuzumab-related anaphylaxis, and no skin rash was found in any patient. Subgroup analysis revealed that the patients who received CCT had more grade 3–4 adverse events as compared to those who did not receive CCT (62.1% vs 33.3%, P=0.045).ConclusionThe regime of nimotuzumab plus IMRT for the treatment of LA-NPC was well tolerated, with encouraging survival data, and it could be an effective treatment alternative for patients with LA-NPC. Further clinical trials are needed to confirm these findings.

Complete Clinical Response after Induction Chemotherapy Followed by Chemoradiotherapy in Nasopharyngeal Carcinoma: Impact on Oncologic Outcomes

Concomitant chemoradiation (RCT) represents the standard of care for locally-advanced nasopharyngeal carcinoma (NPC).Nevertheless induction chemotherapy (IC) followed by RCT is currently an attractive approach.

Oral Mucosa Dose Parameters Predict Grade ≥3 Acute Toxicity in Locally Advanced Nasopharyngeal Carcinoma Treated with Concurrent IMRT and Chemotherapy: A Study Comparing Oral Cavity Versus Mucosal Surface Contouring Techniques

To determine whether volumes based on the contours of the mucosal surface can be used instead of the contours of the oral cavity to predict for grade ≥3 acute oral mucosa toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. A standardized method for the oral cavity (oral cavity contours, OCC) and a novel method for the mucosal surface (mucosal surface contours, MSC) were developed for the oral mucosa and prospectively applied to the radiation treatment plans of 92 patients treated with concurrent IMRT and chemotherapy for LANPC. Dose–volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Grade ≥3 oral mucosa toxicity occurred in 20.7% (19/92) of patients in the study. A highly significant dose–volume relationship between oral mucosa irradiation and acute oral mucosa toxicity was supported by using both oral cavity and mucosal surface contouring techniques. In logistic regression, body weight loss was an independent factor related to grade ≥3 toxicity for OCC and MSC (p=0.017 and 0.005, respectively), and the independent factor of dosimetric parameters for OCC and MSC were V30Gy (p=0.003) and V50Gy (p=0.003), respectively. In the receiver operating characteristics curve, the areas under V30Gy of the OCC curves was 0.753 (p=0.001), and the areas under V50Gy of MSC curves was 0.714 (p=0.004); the cut-off value was 73.155% (sensitivity, 0.842; specificity, 0.671) and 14.32% (sensitivity, 0.842; specificity, 0.575), respectively. DVH analysis of mucosal surface volumes accurately predicts grade ≥3 oral mucosa toxicity in patients with LANPC receiving concurrent IMRT and chemotherapy, but the MSC method is still no better than the OCC method in clinical application.

1101P - Oral mucosa dose parameters predicting grade ≥3 acute toxicity in locally advanced nasopharyngeal carcinoma patients treated with concurrent intensity-modulated radiation therapy and chemotherapy

Background: To determine whether volumes based on the contours of the mucosal surface can be used instead of the contours of the oral cavity to predict for grade ≥3 acute oral mucosa toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. Methods: A standardized method for the oral cavity (oral cavity contours, OCC) and a novel method for the mucosal surface (mucosal surface contours, MSC) were developed for the oral mucosa and prospectively applied to the radiation treatment plans of 92 patients treated with concurrent IMRT and chemotherapy for LANPC. Dose–volume histogram (DVH) data were extracted and analyzed against patient toxicity. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. Results: Grade ≥3 oral mucosa toxicity occurred in 20.7% (19/92) of patients in the study. A highly significant dose–volume relationship between oral mucosa irradiation and acute oral mucosa toxicity was supported by using both oral cavity and mucosal surface contouring techniques. In logistic regression, body weight loss was an independent factor related to grade ≥3 toxicity for OCC and MSC (p=0.017 and 0.005, respectively), and the independent factor of dosimetric parameters for OCC and MSC were V30Gy (p=0.003) and V50Gy (p=0.003), respectively. In the receiver operating characteristics curve, the areas under V30Gy of the OCC curves was 0.753 (p=0.001), and the areas under V50Gy of MSC curves was 0.714 (p=0.004); the cut-off value was 73.155% (sensitivity, 0.842; specificity, 0.671) and 14.32% (sensitivity, 0.842; specificity, 0.575), respectively. Conclusions: DVH analysis of mucosal surface volumes accurately predicts grade ≥3 oral mucosa toxicity in patients with LANPC receiving concurrent IMRT and chemotherapy, but the MSC method is still no better than the OCC method in clinical application. Clinical trial identification: NCT02945878 Legal entity responsible for the study: Yuanyuan Chen Funding: None Disclosure: All authors have declared no conflicts of interest.

Oral Mucosa Dose Parameters Predicting Grade ≥3 Acute Toxicity in Locally Advanced Nasopharyngeal Carcinoma Patients Treated With Concurrent Intensity-Modulated Radiation Therapy and Chemotherapy: An Independent Validation Study Comparing Oral Cavity versus Mucosal Surface Contouring Techniques

PURPOSE: To determine whether volumes based on the contours of the mucosal surface instead of the oral cavity can be used to predict grade ≥3 acute oral mucosa toxicity in patients with locally advanced nasopharyngeal carcinoma (LANPC) treated with concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy. METHODS AND MATERIALS: A standardized method for the oral cavity (oral cavity contours, OCC) and a novel method for the mucosal surface (mucosal surface contours, MSC) were developed for the oral mucosa and prospectively applied to the radiation treatment plans of 92 patients treated with concurrent IMRT and chemotherapy for LANPC. Dose–volume histogram (DVH) data were extracted and then toxicity was analyzed. Receiver operating characteristic analysis and logistic regression were carried out for both contouring methods. RESULTS: Grade ≥3 acute oral mucosa toxicity occurred to 20.7% (19/92) of patients in the study. A highly significant dose–volume relationship between oral mucosa irradiation and acute oral mucosa toxicity was supported by using both oral cavity and mucosal surface contouring techniques. In logistic regression, body weight loss was an independent factor related to grade ≥3 acute toxicity for OCC and MSC (P=.017 and 0.005, respectively), and the independent factor of dosimetric parameters for OCC and MSC were V30Gy (P=.003) and V50Gy (P=.003) respectively. In the receiver operating characteristics curve, the areas under V30Gy of the OCC curves was 0.753 (P=.001), while the areas under V50Gy of MSC curves was 0.714 (P=.004); the cut-off value was 73.155% (sensitivity, 0.842; specificity, 0.671) and 14.32% (sensitivity, 0.842; specificity, 0.575), respectively. CONCLUSION: DVH analysis of mucosal surface volumes accurately predicts grade ≥3 acute oral mucosa toxicity in patients with LANPC receiving concurrent IMRT and chemotherapy, but in clinical practice the MSC method appears no better than the OCC one.

Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a non-endemic area.

The prognostic value of pre-treatment Epstein-Barr Virus (EBV) DNA viral load for non-endemic, locally-advanced, EBV-related nasopharyngeal cancer (NPC) patients is yet to be defined. All patients with EBV encoded RNA (EBER)-positive NPC treated at our Institution from 2005 to 2014 with chemotherapy (CT) concurrent with radiation (RT) +/- induction chemotherapy (ICT) were retrospectively reviewed. Pre-treatment baseline plasma EBV DNA (b-EBV DNA) viral load was detected and quantified by PCR. Median b-EBV DNA value was correlated to potential influencing factors by univariate analysis. Significant variables were then extrapolated and included in a multivariate linear regression model. The same variables, including b-EBV DNA, were correlated with Disease Free Survival (DFS) and Overall Survival (OS) by univariate and multivariate analysis.A total of 130 locally-advanced EBER positive NPC patients were evaluated. Overall, b-EBV DNA was detected in 103 patients (79.2%). Median viral load was 554 copies/mL (range 50–151075), and was positively correlated with T stage (p=0.002), N3a-b vs N0-1-2 stage (p=0.048), type of treatment (ICT followed by CTRT, p=0.006) and locoregional and/or distant disease recurrence (p=0.034). In the overall population, DFS and OS were significantly longer in patients with pre-treatment negative EBV DNA than in positive subjects at the multivariate analysis.Negative b-EBV DNA can be considered as prognostic biomarker of longer DFS and OS in NPC in non-endemic areas. This finding needs confirmation in larger prospective series, with standardized and inter-laboratory harmonized method of plasma EBV DNA quantification.

A phase II trial of induction NAB-paclitaxel and cisplatin followed by concurrent chemoradiotherapy in patients with locally advanced nasopharyngeal carcinoma

ObjectivesNanoparticle albumin-bound paclitaxel (NAB-paclitaxel) was designed to avoid solvent-related toxicities, and improve anti-tumor efficacy via increasing paclitaxel’s intratumoral concentration and its uptake by tumor cells. This trial aimed to determine the safety and efficacy of induction NAB-paclitaxel combined with cisplatin followed by concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Patients and methodsPatients with stage III-IVb NPC received NAB-paclitaxel (260mg/m2) combined with cisplatin (80mg/m2) intravenously on days 1 and 22, followed by cisplatin (80mg/m2) on days 43 and 64, concomitant with intensity-modulated radiation therapy. This trial is registered with the Chinese Clinical Trials Registry, number ChiCTR-ONC-12002615. ResultsFrom July 2010 to November 2013, 36 eligible patients with nonmetastatic stage III-IVb NPC were enrolled. The objective response rates were 97.2% (eight complete responses [CRs] and 27 partial responses [PRs]) and 100% (30 CRs and six PRs) after two cycles of induction chemotherapy (ICT) and CCRT, respectively. With a median follow-up time of 45months, the estimated 3-year progression-free survival and cancer-specific survival were 86.1% (95% confidence interval [CI], 69.8–99.8%) and 91.7% (95% CI, 68.9–100.0%), respectively. The most frequent grade 3–4 toxicities were neutropenia (8.6%) and nausea (8.6%) after ICT and thrombocytopenia (34.3%) and leukopenia (28.6%) after CCRT. ConclusionNAB-paclitaxel combined with cisplatin as an ICT regimen showed encouraging anti-tumor effects and manageable toxicities in LA-NPC. Further randomized controlled trials in phase III of NAB-paclitaxel in patients with LA-NPC are warranted.

Effect observation of sodium cantharidate and vitamin B6 combined with concurrent chemoradiotherapy in treatment of locally advanced nasopharyngeal carcinoma

Objective To study the clinical efficacy of sodium cantharidinate and vitamin B6 injection combined with concurrent chemoradiotherapy in treatment of locally advanced nasopharyngeal carcinoma (LA-NPC). Methods 115 patients with LA-NPC in Shanxi Cancer Hospital were randomly assigned to observation group (61 cases) and control group (54 cases) from February 2014 to April 2016. The patients in the observation group were treated with sodium cantharidate and vitamin B6 injection combined with concurrent chemoradiotherapy. The patients in the control group were treated with concurrent chemoradiotherapy. The differences between the two groups were compared in respect of recent curative effect, the quality of life (QOL) and the adverse reactions. Results The recent effective rate was 93.44% (57/61) in the observation group and 79.63% (43/54) in the control group, and there was significant difference between the two groups (χ2= 4.818, P= 0.049). The improvement rate of QOL was 73.77% (45/61) in the observation group and 53.70% (29/54) in the control group, and there was significant difference between the two groups (χ2= 5.028, P= 0.032). The incidence rates of oral cavity mucous membrane inflammation, hematology toxicity, pharynx and esophagus adverse reactions, the gastrointestinal tract adverse reactions and skin fibrosis in the observation group were lower than those in the control group, and there were significant differences between the two groups (all P < 0.05). Conclusion The recent effect of sodium cantharidinate and vitamin B6 injection combined with concurrent chemoradiotherapy on the patients with LA-NPC is obvious. The comprehensive treatment can also reduce adverse reactions and improve the QOL. Key words: Nasopharyngeal neoplasms; Sodium cantharidinate and vitamin B6; Concurrent chemoradiotherapy

Survival benefit of adding docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy to concurrent chemoradiotherapy for locally advanced nasopharyngeal carcinoma with nodal Stage N2-3.

Concurrent chemoradiotherapy followed by adjuvant chemotherapy (CCRT-AC) has been established as the standard of care in locally advanced nasopharyngeal carcinoma (LA-NPC). The survival benefit of induction chemotherapy (ICT) for LA-NPC remains controversial. We analyzed the efficacy and feasibility of docetaxel, cisplatin and 5-fluorouracil (TPF) ICT followed by CCRT for LA-NPC with nodal Stage N2-3. We performed a retrospective analysis of 28 LA-NPC patients with nodal Stage N2-3 receiving induction TPF followed by CCRT (TPF group; n = 12) or CCRT-AC (CCRT group; n = 16) between October 2006 and May 2016. The median follow-up periods were 36.4 (range 6.7-55.2) and 40.1 months (range 4.3-99.0) for the TPF and CCRT groups, respectively. One- and three-year overall survival for the TPF group vs. the CCRT group were 100% and 100% vs. 94% and 75%, respectively (P = 0.21). The cumulative one- and three-year incidences of locoregional recurrence or progression for the TPF group vs. the CCRT group were 10% and 21% vs. 16% and 32% (P = 0.49), and those of distant metastasis were 0% and 0% vs. 26% and 26%, respectively (P = 0.08). The common Grade 3-4 acute toxicities were neutropenia, anorexia, febrile neutropenia, and stomatitis in the TPF group. The Grade 3-4 late toxicities did not differ significantly between the two groups. This study suggests that induction TPF followed by CCRT might reduce distant metastasis, so this combination may be feasible for the treatment of LA-NPC with nodal Stage N2-3.

Dosimetric and clinical factors for predicting acute radiation oral mucositis in locally advanced nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy with concurrent chemotherapy

Objective To prospectively determine the dosimetric and clinical factors for predicting the risk of acute radiation oral mucositis (ROM) in patients receiving intensity-modulated radiotherapy (IMRT) with concurrent chemotherapy for local advanced nasopharyngeal carcinoma. Methods Ninety-two patients who were treated with IMRT with concurrent chemotherapy from 2015 to 2016 for local advanced nasopharyngeal carcinoma were included in this study, and their acute ROM was scored according to the RTOG criteria. Grade ≥3 ROM was used as a surrogate marker for severe mucositis, which was defined as a toxicity endpoint. The clinical data were reviewed, and the dose-volume histograms (DVHs) of the patients were exported from the IMRT planning system. Optimal thresholds for predicting the incidence of severe ROM were evaluated by the area under the receiver operating characteristic (ROC) curve (AUC). Results The incidence of severe ROM was 21%(19/92). Weight loss and V30 of the oral mucosa were determined as the independent predictors for severe ROM (P=0.017 and 0.003, respectively). The optimal cut-off point and AUC of V30 of the oral mucosa as a predictor for severe ROM were 73.16%(0.842 sensitivity and 0.671 specificity) and 0.753(P=0.001), respectively. Conclusion Weight loss and V30 of the oral mucosa are predictors for severe ROM. Key words: Nasopharyngeal neoplasms/chemoradiotherapy; Radiotherapy, intensity modulated; Radiation oral mucositis; Dose volume histogram

A comparative study of long-term effects between induction chemotherapy and concurrent chemotherapy on patients with local advanced nasopharyngeal carcinoma

Objective:To investigate the long-term efficacy and safety between induction chemotherapy and concurrent chemotherapy in patients with locally advanced nasopharyngeal carcinoma.Method:From January 2006 to January 2011, 190 patients with nasopharyngeal carcinoma were enrolled in the study. Among them, 92 patients received induction chemotherapy and radiotherapy who were classified as the study group, while 98 cases received concurrent radiotherapy and chemotherapy plus adjuvant chemotherapy who were classified as the control group. The general data, overall survival rate, progression free survival rate, acute and chronic adverse reactions were compared between the two groups, and the prognostic factors of local advanced nasopharyngeal carcinoma were analyzed.Result:The 5 year progression free survival (70.7%, 67.3%, P= 0.591) and overall survival (78.3%, 78.6%, P= 0.635) did not differ significantly between the two groups. There was no significant difference in recurrence or metastasis rate between the two groups (29.3%, 35.7%, P= 0.435). The incidence of grade Ⅲ-Ⅳ leukopenia and nausea and vomiting was significantly lower in the study group than that in the control group (P< 0.05), while there was no significant difference in the incidence of late adverse reactions between the two groups (P 0.05). Multivariate analysis showed that age (P= 0.000) and N stage (P= 0.003) were independent prognostic factors for overall survival in patients with locally advanced nasopharyngeal carcinoma.Conclusion:The effect of induction chemotherapy combined with radiotherapy and chemoradiotherapy plus adjuvant chemotherapy was equivalent to locally advanced nasopharyngeal carcinoma, however, the acute adverse reaction rate of induction chemotherapy+radiotherapy was lower. Therefore, induction chemotherapy+radiotherapy may be more effective and safe treatment for patients with local advanced nasopharyngeal carcinoma.

Effect of collimator angles on the dosimetric results of volumetric modulated arc therapy planning for patients with a locally-advanced nasopharyngeal carcinoma

In volumetric modulated arc therapy (VMAT) planning, usually the collimator is rotated to minimize interleaf leakage and the tongue-and-groove effect. The objective of this study was to evaluate the effect of collimator angle on the dosimetric results of VMAT plans for patients with a locally-advanced nasopharyngeal carcinoma (LA-NPC). VMAT treatment planning sets were generated using the same planning parameters, but with different collimator angles for 11 LA-NPC patients. Each set was composed of 10 plans with collimator angles at 0, 5, 10, 15, 20, 25, 35, 40, and 45 degrees. Dosimetric parameters, such as target coverage, organs at risk (OAR), and dose conformity, were analyzed at various collimator angles. With increasing collimator angles, the absorbed doses to the optic apparatus were increased by up to 35% comparing to that at a collimator angle of 0°. The best value of the conformity index (CI) was 0.971 ± 0.023 at collimator angles of 20° and 30°. The worst value of CI was 0.917 ± 0.051 at a collimator angle of 0°. The homogeneity index (HI)95 and HI98 had the best values of 0.106 ± 0.040 and 0.079 ± 0.031, respectively, at a collimator angle of 25°. The worst values of HI95 and HI98 were 0.136 ± 0.039 and 0.105 ± 0.032, respectively, at a collimator angle of of 0°. The maximum doses for some OARs (body, ear, parotid gland, mandible, and brainstem) and the HI did not show any statistically significant differences. However, the mean doses had positive correlations (r = 0.449 ~ 0.773, p<0.001) with the irradiated volume. The CI had a weak positive correlation (r = 0.316, p<0.001) with the irradiated volume. Other comparison parameters were evaluated as functions of the collimator angle. These findings will give useful information for choosing the collimator angle in VMAT plans for patients with a LA-NPC.

Safety and efficacy of lobaplatin combined with 5-fluorouracil as first-line induction chemotherapy followed by lobaplatin-radiotherapy in locally advanced nasopharyngeal carcinoma: preliminary results of a prospective phase II trial

BackgroundDue to improvements in imaging and radiological techniques as well as the use of chemotherapy, distant metastasis has become the predominant mode of treatment failure in patients with locally advanced nasopharyngeal carcinoma (LA-NPC). Platinum-based systemic chemotherapy has shown survival benefits and is now the standard strategy for systemic therapy in patients with LA-NPC. Notably, the third-generation platinum reagent lobaplatin has shown anti-tumor effects in several solid tumors with lower incidences of gastrointestinal, hepatic and renal toxicity relative to other platinum drugs. However, the safety and efficacy of lobaplatin as a first-line regimen in patients with LA-NPC are undetermined.MethodsPatients with stage III–IVa-b NPC received lobaplatin at a dose of 30 mg/m2 on days 1 and 22 combined with a continuous 120-h intravenous injection of 5-fluorouracil at a dose of 4 g/m2 followed by lobaplatin at a dose of 50 mg/m2 on days 43 and 64 concomitant with intensity-modulated radiation therapy. Objective response rates and acute toxicity were assessed based on RECIST (1.1) and CTCAE v.3.0, respectively. Kaplan-Meier analysis was used to calculate survival rates.ResultsFifty-nine patients were enrolled, and 44 patients (74.6%) received allocated cycles of chemotherapy. The objective response rates were 88.1% (95% confidence interval [CI], 0.77 to 0.95) and 100% after induction chemotherapy (ICT) and concurrent chemoradiotherapy (CRT), respectively. With a median follow-up period of 44 months, the 3-year estimated progression-free survival and overall survival were 86.4% (95% CI, 69.8 to 98.8) and 94.9% (95% CI, 89.5 to 100), respectively. The most common grade 3–4 toxicities were neutropenia (8.5%) and thrombocytopenia (40.7%) after ICT and CRT, respectively.ConclusionLobaplatin combined with 5-fluorouracil followed by lobaplatin-RT treatment showed encouraging anti-tumor effects with tolerable toxicities in patients with LA-NPC. Randomized controlled trials of lobaplatin in patients with LA-NPC are warranted.Trial registrationThis trial was registered with the Chinese Clinical Trials Registry and approved on March 31st, 2012, number ChiCTR-ONC-12002060.

Nasopharyngeal carcinoma: Experience and treatment outcome with radical conformal radiotherapy from a tertiary care center in India.

The majority of nasopharyngeal carcinoma (NPC) reports on the outcome and prognostic factors are from endemic high-risk regions. Data on the outcome of Indian patients are sparse. In this study, we retrospectively analyzed the outcome of NPC patients treated radically with conformal radiotherapy (RT). The primary objective was to assess the outcome, and the secondary objectives were to assess treatment-related morbidities and the impact of various prognostic factors on the outcome. Sixty-eight patients with biopsy-proven NPC who received radical conformal RT, i.e., three-dimensional conformal RT or intensity-modulated RT (IMRT) during 2004-2013 were analyzed. All patients received conformal RT with or without chemotherapy. Statistical analysis was performed using Statistical Package for the Social Sciences (SPSS, version 20.0) software, IBM, USA. Survival analysis was performed using Kaplan-Meier method. For calculating the hazard ratio of the prognostic factors, univariate and multivariate Cox regression analyses were done. Chi-square test was used to determine the association. In this study, with a median follow-up of 43 months, the overall survival (OS), disease-free survival, and cause-specific survival were 91, 85.2, and 98.4% at 2 years and 78.3, 72.8, and 88.2% at 3 years, respectively. The locoregional failure was low (3%), and the 5-year cause-specific survival with chemoradiation was excellent (79%), even with 50% of the patients being nonmetastatic Stage IV. Eleven out of 12 failures were distant metastases. The treatment-related late morbidities were acceptable and better with IMRT. Significant prognostic factors affecting the outcome were composite stage of the disease and the interval between diagnosis and treatment initiation. In locally-advanced NPC, excellent local control is possible with modern conformal RT with concurrent chemotherapy. Distant metastases remain a therapeutic challenge despite systemic chemotherapy. Novel systemic therapies are needed in the future for improving the OS of these patients.

Abstract 5038: The repression of the extracellular matrix protein TGFBI induces chemoresistance in nasopharyngeal carcinoma

Abstract Introduction: Nasopharyngeal carcinoma (NPC) is a malignancy that is strongly associated with Epstein-Barr virus (EBV). The five-year overall survival (OS) rate of locally-advanced NPC patients is ∼65%. Therapeutic options for such patients are limited; ionizing radiation is the primary mode of therapy for early-stage NPC, while chemoradiotherapy is used for more advanced stages. The use of chemotherapy (combined with radiation) provides a modest benefit in OS, but causes significant toxicities. The major cause of death in NPC is distant metastasis (DM), which remains a clinical challenge. In order to identify novel mechanisms underlying this process, our laboratory has recently completed global RNA sequencing of NPC samples which were fully clinically annotated. The extracellular matrix protein TGFBI (Transforming Growth Factor, Beta-Induced) was identified as a potential marker for chemoresistance. The objective of this study was to elucidate the role of TGFBI, and acquire greater insight into the biological pathways leading to chemoresistance and contributing to DM in NPC. Methods: Nasopharyngeal cell lines including NP69 (normal nasopharyngeal, SV-40 immortalized), and C666-1 (NPC, EBV positive) were used to assess the differential expression of TGFBI between normal and malignant cells. TGFBI under-expressing NP69 cells were engineered using shRNA vectors, and the impact of the loss of TGFBI expression was assessed by cell death, clonogenic, and migration assays. Downstream target gene expression was evaluated by quantitative real-time PCR (qRT-PCR) and Western blot. C666-1 cells, which had no expression of TGFBI (RNA or protein), were used as controls. Results: RNA-seq data identified poorer distant relapse-free survival in chemoradiotherapy-treated patients with low TGFBI expression vs. those with high TGFBI expression. In concordance with this observation, in vitro down-regulation of TGFBI induced cisplatin resistance via the phosphorylation of Akt and PTEN. TGFBI downregulation also increased cellular migration in spheroid cultures. Furthermore, TGFBI was identified to be a target of miR-449b, one of the 4 microRNAs in a DM prognostic signature that was previously identified by our group (Oncotarget 6:4537, 2015). In turn, over-expression of miR-449b in nasopharyngeal cells increased phospho-Akt expression, phenocopying the results observed in the TGFBI experiments. Conclusion: Together, these data suggest that the miR-449∼TGFBI-Akt axis plays a significant role in both treatment resistance and metastasis in NPC. Further studies will allow us to elucidate additional components of this pathway, and identify novel therapeutic targets which can benefit future patients with NPC. Citation Format: Pierre-Antoine Bissey, Jeff W. Bruce, Jacqueline Law, Kenneth W. Yip, Fei-Fei Liu. The repression of the extracellular matrix protein TGFBI induces chemoresistance in nasopharyngeal carcinoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5038.

Radiation plus concurrent nimotuzumab versus CDDP in locally advanced nasopharyngeal cancer: Results of a phase III randomised trial.

6002Background: Nimotuzumab, a novel humanized anti-EGFR monoclonal antibody, is one of the recommended concurrent regimen with radiotherapy (RT)for locally advanced nasopharyngeal cancer (LA-NPC)b...