Low-risk Nasopharyngeal Carcinoma Research Articles

Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma

Concurrent chemoradiotherapy has been the standard treatment for stage II nasopharyngeal carcinoma (NPC) based on data using 2-dimensional conventional radiotherapy. There is limited evidence for the role of chemotherapy with use of intensity-modulated radiation therapy (IMRT). To assess whether concurrent chemotherapy can be safely omitted for patients with low-risk stage II/T3N0 NPC treated with IMRT. This multicenter, open-label, randomized, phase 3, noninferiority clinical trial was conducted at 5 Chinese hospitals, including 341 adult patients with low-risk NPC, defined as stage II/T3N0M0 without adverse features (all nodes <3 cm, no level IV/Vb nodes; no extranodal extension; Epstein-Barr virus DNA <4000 copies/mL), with enrollment between November 2015 and August 2020. The final date of follow-up was March 15, 2022. Patients were randomly assigned to receive IMRT alone (n = 172) or concurrent chemoradiotherapy (IMRT with cisplatin, 100 mg/m2 every 3 weeks for 3 cycles [n = 169]). The primary end point was 3-year failure-free survival (time from randomization to any disease relapse or death), with a noninferiority margin of 10%. Secondary end points comprised overall survival, locoregional relapse-free survival, distant metastasis-free survival, adverse events, and health-related quality of life (QOL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (QLQ-C30; range, 0-100 points; minimum clinically important difference ≥10 for physical function, symptom control, or health-related QOL; higher score indicates better functioning and global health status or worse symptoms). Among 341 randomized patients (mean [SD] age, 48 [10] years; 30% women), 334 (98.0%) completed the trial. Median follow-up was 46 months (IQR, 34-58). Three-year failure-free survival was 90.5% for the IMRT-alone group vs 91.9% for the concurrent chemoradiotherapy group (difference, -1.4%; 1-sided 95% CI, -7.4% to ∞; P value for noninferiority, <.001). No significant differences were observed between groups in overall survival, locoregional relapse, or distant metastasis. The IMRT-alone group experienced a significantly lower incidence of grade 3 to 4 adverse events (17% vs 46%; difference, -29% [95% CI, -39% to -20%]), including hematologic toxicities (leukopenia, neutropenia) and nonhematologic toxicities (nausea, vomiting, anorexia, weight loss, mucositis). The IMRT-alone group had significantly better QOL scores during radiotherapy including the domains of global health status, social functioning, fatigue, nausea and vomiting, pain, insomnia, appetite loss, and constipation. Among patients with low-risk NPC, treatment with IMRT alone resulted in 3-year failure-free survival that was not inferior to concurrent chemoradiotherapy. ClinicalTrials.gov Identifier: NCT02633202.

Endostar combined with intensity-modulated radiotherapy in low-risk local advanced nasopharyngeal carcinoma: A phase II, randomized, multicentric clinical trial.

6050 Background: A Phase II, randomized, prospective, multicentric trial was conducted to evaluate the efficacy and safety of Endostar plus radiotherapy in patients with low-risk local advanced nasopharyngeal carcinoma (NPC). This study reported the preliminary results of NCT02237924. Methods: From 09/2014 to 08/2016, patients with low-risk local advanced NPC were randomly treated with Endostar plus radiotherapy (ERT group, n=60) and concurrent chemoradiotherapy (CCRT group, n=60). Primary endpoint was the 5-year overall survival (OS) rate. The secondary endpoints were 3-year OS rate, progression free survival (PFS) rate, loco-regional recurrence free survival (LRRFS) rate and distance metastasis free survival (DMFS) rate. Results: After a median follow-up of 47 months, 3-year OS rate were 93.2% and 79.3% (p=0.032), 3-year PFS rate were 89.8% and 70.6% (p=0.011), 3-year DMFS rate were 93.2% and 80.7%, in two groups, respectively (P=0.042). 3-year LRRFS rate were 96.6% and 92.0% in two groups, respectively (but P=0.565). For short-term curative effects, CR rate were 71.2% and 60.0% for primary tumor, 74.6％and 63.3％for cervical lymph nodes, in two groups, respectively (P &lt; 0.05). Moreover, the incidences of adverse events were significantly lower in ERT group compared with in CCRT group. The grade 3/4 Hyponatraemia (0 [0%] vs 3 [5%], p=0·04), the grade 1/2 vomiting (10 [16.7%] vs 52 [86.7%], p=0.000), dry mouth (45 [75.0%] vs 56 [93.3%], p=0.012), leukopenia (22 [36.7%] vs 42 [70.0%], p=0.000) and weight loss (30 [50.0%] vs 45 [75.0%], p=0.005). No patients died of treatment-related causes. Conclusions: OS, PFS, and DMFS rates can be improved, adverse events be reduced, with better tolerability, by Endostar plus radiotherapy, when compared to concurrent chemoradiotherapy for local advanced low-risk NPC. Clinical trial information: NCT02237924. [Table: see text]

Nomogram Predicting the Benefits of Adding Concurrent Chemotherapy to Intensity-Modulated Radiotherapy After Induction Chemotherapy in Stages II-IVb Nasopharyngeal Carcinoma.

BackgroundTo compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus induction chemotherapy plus radiotherapy (IC+RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).Patients and MethodsOne thousand three hundred twenty four patients with newly-diagnosed NPC treated with IC+CCRT or IC+RT were enrolled. Progression-free survival (PFS), distant metastasis-free survival (DMFS), overall survival (OS), locoregional relapse-free survival (LRFS), and acute toxicities during radiotherapy were compared using propensity score matching (PSM). A nomogram was developed to predict the 3- and 5-year PFS with or without concurrent chemotherapy (CC).ResultsPSM assigned 387 patients to the IC+CCRT group and IC+RT group, respectively. After 3 years, no significant difference in PFS (84.7 vs. 87.5%, P = 0.080), OS (95.5 vs. 97.6%, P = 0.123), DMFS (89.7 vs. 92.8%, P = 0.134), or LRFS (94.0 vs. 94.1%, P = 0.557) was noted between the groups. Subgroup analysis indicated comparable survival outcomes in low-risk NPC patients (II–III with EBV DNA <4,000 copies/ml) between the groups, although IC+RT alone was associated with fewer acute toxicities. However, IC+CCRT was associated with significantly higher 3−year PFS, OS, DMFS, and LRFS rates, relative to IC+RT alone, in high-risk NPC patients (IVa-b or EBV DNA ≥4,000 copies/ml). Multivariate analysis showed that T category, N category, EBV DNA level, and treatment group were predictive of PFS, and were hence incorporated into the nomogram. The nomogram predicted that the magnitude of benefit from CC could vary significantly.ConclusionsIC+RT had similar efficacy as IC+CCRT in low-risk NPC patients, but was associated with fewer acute toxicities. However, in high-risk patients, IC+CCRT was superior to IC+RT.

Endostar Combined with Intensity-Modulated Radiotherapy in Low-Risk Local Advanced Nasopharyngeal Carcinoma: A Phase II, Randomized, Multicentric Clinical Trial

Background: A Phase II, randomized, prospective, multicentric trial (NCT02237924) was conducted to evaluate the efficacy and safety of Endostar plus radiotherapy in patients with low-risk local advanced nasopharyngeal carcinoma (NPC). Methods: From 09/2014 to 08/2016, patients with low-risk local advanced NPC were randomly treated with Endostar plus radiotherapy (ERT group, n=60) and concurrent chemoradiotherapy (CCRT group, n=60). Primary endpoint was the 5-year overall survival (OS) rate. The secondary endpoints were 3-year progression free survival (PFS) rate, OS rate, loco-regional recurrence free survival (LRRFS) rates and distance metastasis free survival (DMFS) rates. Findings: After a median follow-up of 47 months, 3-year OS rates were 93.2% and 79.3%, 3-year PFS rates were 89.8% and 70.6%, 3-year DMFS rates were 93.2% and 80.7%, in two groups, respectively (P 0.05). Moreover, the incidences of complications were significantly lower in ERT group. For short-term curative effects, CR rates were 70.0% and 60.0% for primary tumor, 73.3%and 65.0% for cervical lymph nodes, in two groups, respectively (P 0.05). Interpretation: OS, PFS, and DMFS rates can be improved, adverse events be reduced, with better tolerability, by Endostar plus radiotherapy, when compared to concurrent chemoradiotherapy for local advanced low-risk NPC. Trial Registration: (NCT02237924). Funding Statement: This work was supported by National Natural Science Foundation of China (No. 81760542), the Projects for Research and Development of Medical and Health Appropriate Technology of Guangxi Zhuang Autonomous Region (No. S2018087), the Key Research and Development Program of Guangxi (No. Guike AB18281003), Guangxi Medical University Training Program for Distinguished Young Scholars, and Medical Excellence Award Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University, “139” Program for high-level medical talents in Guangxi, Innovation Team of the First Affiliated Hospital of Guangxi Medical University. Guangxi Science and Technology Program Project (GK AD17129013), Simcere. Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of Guangxi Medical University. All procedures performed in the study involving human participants were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments. Written informed consent was obtained from the patient and his/her immediate families.

290O - Long-term results of phase II trial of reduced modified clinical target volume in low-risk nasopharyngeal carcinoma treated with intensity modulated radiotherapy

BackgroundIntensity modulated radiation therapy (IMRT) is the standard of care for nasopharyngeal carcinoma (NPC). Part of the IMRT quality assurance process involves accurate target volume delineation, which is crucial for local control and survival. Current practice utilizes a uniform contouring method for clinical target volume (CTV) for all stages of NPC. Here, we conducted a single-arm phase 2 trial investigating the tumor control rates of reduced CTV margins and corresponding doses in low-risk, early-stage NPC. MethodsPatients with biopsy-proven stage I-IIb (6th UICC/AJCC) NPC were enrolled. All patients were treated with IMRT alone. Two CTVs (CTV1 [high risk] and CTV2 [low risk]) were outlined; CTV1 was defined by grossly identified tumour (on MRI or CT) plus 5-mm margin (3-mm posteriorly); CTV2 was CTV1 plus 5-mm margin (3-mm posteriorly). 60 Gy and 50–54 Gy in 30 fractions were prescribed to CTV1 and CTV2, respectively. Primary end-point was locoregional recurrence free survival (LRRFS). ResultsFrom May 2001 to August 2006, 103 patients were recruited; all patients completed IMRT as planned (time duration 39-61 days). At a median follow-up of 12.6 years, five patients developed locoregional failures; of which one was in-field, and four were regional recurrence (two in-field and two marginal). 10-year LRRFS, distant metastasis free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 95.0% and 94.1%, 94.0% and 91.1%, respectively. The most common grade 1-2 late toxicities included subcutaneous fibrosis (79.6%), hearing loss (53.4%) and skin dystrophy (43.2%); grade 3 included subcutaneous fibrosis (2.9%) and hearing loss (2.9%); and no grade 4 late toxicity. ConclusionsReduced CTV margins and corresponding doses results in optimal longterm tumour control, with minimal late adverse events. Clinical trial identificationNCT03839602. Legal entity responsible for the studyProf. Chong Zhao. FundingHas not received any funding. DisclosureM.L.K. Chua: Honoraria (self), Advisory / Consultancy: Janssen, Astellas, Varian, Ferring Singapore and AstraZeneca; Research grant / Funding (institution): Ferring Singapore, GenomeDx Biosciences, Varian, MedLever. All other authors have declared no conflicts of interest.

1141P - Long-term results of phase II trial of reduced modified clinical target volume in low-risk nasopharyngeal carcinoma treated with intensity modulated radiotherapy

BackgroundIntensity modulated radiation therapy (IMRT) is the standard of care for nasopharyngeal carcinoma (NPC). Part of the IMRT quality assurance process involves accurate target volume delineation, which is crucial for local control and survival. Current practice utilizes a uniform contouring method for clinical target volume (CTV) for all stages of NPC. Here, we conducted a single-arm phase 2 trial investigating the tumor control rates of reduced CTV margins and corresponding doses in low-risk, early-stage NPC. MethodsPatients with biopsy-proven stage I-IIb (6th UICC/AJCC) NPC were enrolled. All patients were treated with IMRT alone. Two CTVs (CTV1 [high risk] and CTV2 [low risk]) were outlined; CTV1 was defined by grossly identified tumour (on MRI or CT) plus 5-mm margin (3-mm posteriorly); CTV2 was CTV1 plus 5-mm margin (3-mm posteriorly). 60Gy and 50–54Gy in 30 fractions were prescribed to CTV1 and CTV2, respectively. Primary end-point was locoregional recurrence free survival (LRRFS). ResultsFrom May 2001 to August 2006, 103 patients were recruited; all patients completed IMRT as planned (time duration 39-61 days). At a median follow-up of 12.6 years, five patients developed locoregional failures; of which one was in-field, and four were regional recurrence (two in-field and two marginal). 10-year LRRFS, distant metastasis free survival (DMFS), disease specific survival (DSS) and overall survival (OS) were 95.0% and 94.1%, 94.0% and 91.1%, respectively. The most common grade 1-2 late toxicities included subcutaneous fibrosis (79.6%), hearing loss (53.4%) and skin dystrophy (43.2%); grade 3 included subcutaneous fibrosis (2.9%) and hearing loss (2.9%); and no grade 4 late toxicity. ConclusionsReduced CTV margins and corresponding doses results in optimal long-term tumour control, with minimal late adverse events. Clinical trial identificationNCT03839602. Legal entity responsible for the studyChong Zhao. FundingNational Natural Science Foundation of China [No. 81872469]; Science and Technology Project of Guangdong Province [No. 2014A020212433]. DisclosureM.L.K. Chua: Honoraria (institution), Advisory / Consultancy: Janssen, Astellas, Varian, Ferring Singapore and AstraZeneca; Research grant / Funding (institution), Structured research agreement/Research funding - Ferring Singapore, GenomeDx Biosciences, Varian, MedLever.: Ferring Singapore, GenomeDx Biosciences, Varian, MedLever. All other authors have declared no conflicts of interest.

Childhood Nasopharyngeal Carcinoma: State-of-the-Art, and Questions for the Future.

In children, nasopharyngeal carcinoma (NPC) is a very rare tumor, mostly Epstein-Barr Virus related and quite always diagnosed at a locally advanced stage. With current protocols associating induction cisplatin-based chemotherapy and concomitant chemoradiotherapy, prognosis is excellent with overall survival higher than 85%. However, long-term toxicities are frequent. Improvement in radiation therapy modalities like intensity-modulated radiation therapy and new strategies with radiation dose adaptation to chemotherapy response have been introduced to reduce acute and long-term toxicities. Actually, 2 main questions remain: is it possible to pursue a therapeutic deescalation in children with low-risk NPC or very good response to induction chemotherapy in order to reduce the risk of late effects? Could an immunologic maintenance treatment improve prognosis of children with high-risk NPC? International collaborative groups and prospective trials including biological studies are necessary to answer these questions to improve childhood NPC treatment and knowledge.

The Feasibility of Selectively Omission of Radiation to Level IB Lymph Nodes in Low-Risk Nasopharyngeal Carcinoma

The Feasibility of Selectively Omission of Radiation to Level IB Lymph Nodes in Low-Risk Nasopharyngeal Carcinoma

The feasibility analysis of omission of elective irradiation to level IB lymph nodes in low-risk nasopharyngeal carcinoma based on the 2013 updated consensus guideline for neck nodal levels

BackgroundLevel IB metastasis is rare in nasopharyngeal carcinoma (NPC). The purpose of this study is to investigate the high-risk factors for level IB metastasis and evaluate the feasibility of omission of elective irradiation to level IB in the low-risk subgroups in NPC.MethodsThis retrospective study identified 532 patients with NPC treated by definitive radiation in our institution from 2009 to 2010. Level IB nodes were electively irradiated based on the physician’s decision. Diagnostic head and neck MRIs were reviewed. The involvements of nodal levels were evaluated according to 2013 updated guidelines of RTOG. The correlations of level IB metastasis and other factors were studied using Chi-square test and logistic regression model. Log-rank tests were used to compare survival rates. Cox proportional-hazards models were used to evaluate the effect of various factors. Patient-reported xerostomia was recoded in every follow-up and the extents of delayed xerostomia at 1 year post-radiation were compared between those with/without elective level IB irradiation.ResultsN stage, bilateral nodal metastasis, level II involvement, level IIA involvement, level IIA with multiple levels involvement, maximal axial diameter (MAD) of level IIA nodes > 20 mm, MAD of neck lymph nodes > 30 mm, necrosis of level IIA nodes, extracapsular spread of level IIA correlated with level IB metastasis by univariate analysis. In multivariate analysis (MVA), bilateral nodal involvement, MAD of level IIA nodes > 20 mm or extracapsular spread of level IIA nodes, were independent predictive factors for level IB metastasis. Patients without either these factors were denoted low-risk group and the rest high-risk group. Of the low-risk group, there was no significant difference of regional control and overall survival (OS) between those with or without elective irradiation. The percentage of level IB recurrence of those without elective irradiation was 0.46%. Elective level IB irradiation was not significant upon MVA both for regional control and OS. Of the high-risk group, elective level IB irradiation was marginal significant for regional control, but not for OS upon MVA. No regional recurrence located at level IB. Overall, omission of elective irradiation to level IB reduced the mean doses of submandibular glands, but did not improve patient-reported xerostomia.ConclusionFor patients without high-risk factors of level IB metastasis, omission of elective level IB irradiation did not impair regional control and OS in NPC.

A phase II randomized, multicentric clinical trail comparing recombinant human endostatin plus intensity-modulated radiotherapy versus concurrent chemoradiotherapy in locally advanced low-risk nasopharyngeal carcinoma.

6063 Background: A prospective, randomized, and multicentric phase II study was performed to evaluate the short-term efficacy and safety of Endostar plus intensity-modulated radiotherapy (IMRT) versus concurrent chemoradiotherapy(CCRT) in locally advanced low-risk nasopharyngeal carcinoma(NPC). Methods: From September 2014 to August 2016, 120 patients with low-risk NPC at stages III-IVa from 9 centers were randomly divided into experimental group (Endostar plus radiotherapy (ERT); n = 60) and control group (CCRT; n = 60). ERT patients were given Endostar (7.5 mg/m2/day) by continuous intravenous infusion (CIV) from 5 days before radiotherapy for consecutive 10 days for 2 cycles with an interval of 14 days. Then, ERT patients received 2 cycles of 10 days of maintenance treatment with Endostar after radiotherapy. The CCRT patients were given cisplatin (100 mg/m2) on days 1, 22, and 43 for 3 cycles. Immediate and 3-month efficacy and adverse effects were evaluated between the two groups. ClinicalTrials registration number was NCT02237924. Results: All patients were eligible for toxicity and response analysis. Regarding immediate efficacy, the complete response(CR) rates were 45.0% for ERT arm and 33.3% for CCRT arm in nasopharynx (P = 0.190), and 43.3% for ERT arm and 36.7% for CCRT arm in regional nodes (P = 0.456). Three months after RT, the CR rates were 71.2% for ERT arm and 60.0% for CCRT arm in nasopharynx (P = 0.151), and 74.6% for ERT arm and 63.3% for CCRT arm in regional nodes (P = 0.172). The rate and severity of leukopenia, hemoglobin reduction and thrombocytopenia in ERT arm were significantly lower than CCRT arm (P &lt; 0.01). The occurrence rates of Xerostomia, oral mucositis, nausea / vomiting, constipation and weight loss in ERT arm were significantly lower than those in CCRT arm (P &lt; 0.01). Conclusions: The present study demonstrates that ERT has similar short-term efficacy on locally advanced low-risk NPC compared with CCRT, but the acute adverse effects of ERT are fewer, and the compliance and tolerability of patients are better. Clinical trial information: NCT02237924.

Propensity score matching analysis of cisplatin-based concurrent chemotherapy in low risk nasopharyngeal carcinoma in the intensity-modulated radiotherapy era.

Patients with stage II nasopharyngeal carcinoma were reported to benefit from adding cisplatin-based concurrent chemotherapy to two-dimensional conventional radiotherapy. But this benefit becomes uncertain in the intensity-modulated radiotherapy (IMRT) era, owing to its significant advantage. We enrolled 661 low risk (T1N1M0, T2N0-1M0 or T3N0M0, the 2010 UICC/AJCC staging system) patients who underwent IMRT with or without concurrent chemotherapy. Particularly, patients with IMRT alone or IMRT plus cisplatin-based concurrent chemotherapy were equally matched using propensity-score matching method. Overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were assessed with Kaplan-Meier method, log-rank test and Cox regression. Among 661 patients, IMRT alone achieved parallel OS (P = 0.379), DMFS (P = 0.169) and LRFS (P = 0.849) to IMRT plus concurrent chemotherapy. In the propensity-matched cohort of 482 patients, similar survival were observed between both arms (4-years OS 97.4% vs 96.1%, P = 0.134; DMFS 96.5% vs 95.1%, P = 0.763; LRFS 93.8% vs 91.5%, P = 0.715). In multivariate analysis, cisplatin-based concurrent chemotherapy did not lower the risk of death, distant metastasis or locoregional relapse. And this association remained unchanged in subgroups by age, sex, histology and stage. In this study, low risk nasopharyngeal carcinoma patients who underwent IMRT could not benefit from cisplatin-based concurrent chemotherapy.

Concurrent chemoradiotherapy with adjuvant chemotherapy for high-risk nasopharyngeal carcinoma

Objectives To evaluate the impact of invasion of the prevertebral or parapharyngeal spaces and large tumor volume on treatment outcomes in patients with nasopharyngeal carcinoma (NPC). Methods A total of 105 patients with newly diagnosed NPC were enrolled in this study. TNM stage and presence of invasion of the prevertebral or parapharyngeal spaces were recorded. All patients received a total dose of 70–75 Gy. Results After controlling for age, sex, and chemotherapy status, invasion of the prevertebral or parapharyngeal spaces and large primary tumor volume produced a significantly increased hazard ratio for distant metastasis and recurrence. We defined patients with two or more such prognostic factors as high-risk patients, in whom the 3-year metastasis-free survival rate, with and without adjuvant chemotherapy, was 100% and 69.6%, respectively ( P = 0.02). Their 3-year recurrence-free survival rate, with and without adjuvant chemotherapy, was 93.3% and 70.2% ( P = 0.09). This benefit was not observed in low-risk NPC patients. Conclusion NPC patients with any two or more of the factors, involvement of the prevertebral space, large primary tumor volume, or advanced parapharyngeal space invasion, had more recurrence and poor survival rates and benefited from concurrent chemoradiotherapy followed by adjuvant chemotherapy.