Advanced Nasopharyngeal Cancer Research Articles

Comparison of weekly versus triweekly cisplatin delivered concurrently with radiation therapy in patients with locally advanced nasopharyngeal cancer: A multicenter randomized phase II trial (KCSG-HN10-02)

PurposeTriweekly delivery of cisplatin concurrent with a course of radiation therapy (RT) has been the standard regimen for treatment of locally advanced nasopharyngeal carcinoma (NPC) despite a high level of concern regarding treatment-related complications. We conducted a randomized phase II study to compare weekly and triweekly cisplatin delivery during RT with respect to efficacy and toxicity profiles. Material and methodsPatients with locally advanced NPC (stage II–IVb) were randomly assigned to a regimen of either seven doses of cisplatin (40mg/m2) given once a week or three doses of cisplatin (100mg/m2) given every 3weeks concurrently during RT. ResultsOf 109 eligible patients, 53 were assigned to the weekly regimen and 56 to the triweekly regimen. The two groups were comparable with respect to demographic and clinical characteristics. There were no significant differences in mean RT dose (68.3Gy vs. 67.3Gy, p=0.559) and mean cisplatin dose (248.9mg/m2vs. 256.6mg/m2, p=0.433) between the two regimens. The primary endpoint was 3-year progression-free survival, which was not different between the regimens (64.9% vs. 63.8%, p=0.074). Overall, the occurrence of grade 3–4 toxicities was similar between the two arms (47.2% vs. 39.3%, p=0.443). Quality of life (QoL) related to functional outcomes 3weeks after treatment completion was better for the weekly regimen. ConclusionsAlthough no definitive conclusions can be made, a once-weekly cisplatin regimen appears to be associated with improved QoL and is not inferior to the standard triweekly regimen with respect to efficacy and toxicity profiles.

Screening for nasopharyngeal cancer.

Nasopharyngeal cancer is endemic in a few well-defined populations. The prognosis for advanced nasopharyngeal cancer is poor, but early-stage disease is curable and a high survival rate can be achieved. Screening for early-stage disease could lead to improved outcomes. Epstein-Barr virus (EBV) serology and nasopharyngoscopy are most commonly used for screening. The efficacy and true benefit of screening remain uncertain due to potential selection, lead-time and length-time biases. To determine the effectiveness of screening of asymptomatic individuals by EBV serology and/or nasopharyngoscopy in reducing the mortality of nasopharyngeal cancer compared to no screening. To assess the impact of screening for nasopharyngeal cancer on incidence, survival, adverse effects, cost-effectiveness and quality of life. The Cochrane Ear, Nose and Throat Disorders Group (CENTDG) Trials Search Co-ordinator searched the CENTDG Trials Register; Central Register of Controlled Trials (CENTRAL 2015, Issue 6); PubMed; EMBASE; CINAHL; Web of Science; Clinicaltrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 6 July 2015. Randomised controlled trials (RCT) and controlled clinical trials (CCT) evaluating screening for nasopharyngeal cancer versus no screening. Randomisation either by clusters or individuals was acceptable. We used the standard methodological procedures expected by The Cochrane Collaboration. Our primary outcome measure was nasopharyngeal cancer-specific mortality. Secondary outcomes were incidence of nasopharyngeal cancer by stage and histopathological classification at diagnosis, survival (two-year, three-year, five-year and 10-year), harms of screening (physical and psychosocial), quality of life (via validated tools such as the SF-36 and patient satisfaction), cost-effectiveness and all-cause mortality. We identified no trials that met the review inclusion criteria. We retrieved 31 full-text studies for further investigation following the search. However, none met the eligibility criteria for a RCT or CCT investigation on the efficacy of screening for nasopharyngeal cancer. No data from RCTs or CCTs are available to allow us to determine the efficacy of screening for nasopharyngeal cancer, or the cost-effectiveness and cost-benefit of a screening strategy. High-quality studies with long-term follow-up of mortality and cost-effectiveness are needed.

Radiation dose to the tongue and velopharynx predicts acoustic-articulatory changes after chemo-IMRT treatment for advanced head and neck cancer

The aim of this study was to investigate to what extent changes in speech after C-IMRT treatment are related to mean doses to the tongue and velopharynx (VP). In 34 patients with advanced hypopharyngeal, nasopharyngeal, or oropharyngeal cancer, changes in speech from pretreatment to 10 weeks and 1 year posttreatment were correlated with mean doses to the base of tongue (BOT), oral cavity (OC) and tonsillar fossa/soft palate (VP). Differences in anteroposterior tongue position, dorsoventral degree of tongue to palate or pharynx constriction, grooving, strength, nasality, and laryngeal rise, were assessed by acoustic changes in three speech sounds that depend on a (post-) alveolar closure or narrowing (/t/, /s/, /z/), three with a tongue to palate/pharyngeal narrowing (/l/, /r/, /u/), and in vowel /a/ at comfortable and highest pitch. Acoustically assessed changes in tongue positioning, shape, velopharyngeal constriction, and laryngeal elevation were significantly related to mean doses to the tongue and velopharynx. The mean dose to BOT predicted changes in anteroposterior tongue positioning from pre- to 10-weeks posttreatment. From pretreatment to 1-year, mean doses to BOT, OC, and VP were related to changes in grooving, strength, laryngeal height, nasality, palatalization, and degree of pharyngeal constriction. Changes in speech are related to mean doses to the base of tongue and velopharynx. The outcome indicates that strength, motility, and the balance between agonist and antagonist muscle forces change significantly after radiotherapy.

Evaluation of salivary function by sialoscintigraphy in locally advanced nasopharyngeal cancer patients after intensity modulated radiotherapy.

This study aimed to evaluate the salivary gland function changes by sialoscintigraphy in locally advanced nasopharyngeal cancer (NPC) after intensity modulated radiotherapy (IMRT). Salivary function was assessed by sialoscintigraphy. Quantitative sialoscintigraphy was performed in 24 NPC patients prior to and after IMRT. Results were categorized in four groups according to the duration of treatment. The sialoscintigraphy parameters were examined. Sialoscintigraphy showed a significant difference in the secretion of each interval groups. The parameters of scintigraphy, except maximum accumulation (MA) of submandibular glands, decreased first after radiotherapy, and then recovered. However, the MA of submandibular glands was continuously downhill after radiation. The sialoscintigraphy parameters of each gland changed with the different radiation dose and follow-up intervals. The salivary function was influenced after radiotherapy in locally advanced NPC, especially, in the submandibular gland. Strategies to improve the salivary function should be assessed.

Correlation between ERCC1 expression and concurrent chemotherapy and radiotherapy in patients with locally advanced nasopharyngeal cancer.

In this study, the expression of DNA excision repair cross-complementing gene 1 (ERCC1) in local advanced nasopharyngeal carcinoma has been correlated with the efficacy of concurrent chemoradiotherapy. A total of 76 patients diagnosed with undifferentiated nasopharyngeal carcinoma diagnosed by nasopharyngeal biopsy and undergoing single-agent cisplatin chemotherapy (80 mg/m(2)) with concurrent radiotherapy (on the first, twenty-second, and forty-third day, 5 times per week, mean dose 74 Gy, range 70-78 Gy) at the Affiliated Cancer Hospital of Guangxi Medical University between January and December 2010 were included. After chemoradiotherapy, outcomes and long-term survival were evaluated. Immunohistochemistry was used to detect expression of ERCC1 protein in nasopharyngeal carcinoma. The relationship between the expression of ERCC1 and efficacy of concurrent chemoradiotherapy and long-term survival were analyzed. ERCC1 was expressed in 42.1% of cases. The expression of ERCC1 was correlated with T stage and clinical staging (P < 0.05), but not with gender, age, or N stage. The response rate in the ERCC1-positive and ERCC1-negative groups was 75.0% and 97.7%, respectively (P < 0.05). In the 72 cases with follow-up available, 1-, 2-, and 3-year survival rates were 91.0, 83.3, and 79.0%; they were 92.4, 87.8, 80.5%, respectively, in the ERCC1-positive group, and 87.9, 77.4, 77.4%, respectively, in the ERCC1-negative group. The expression of ERCC1 may be a sensitive prognostic indicator of concurrent chemoradiotherapy in locally advanced nasopharyngeal carcinoma.

Retrospective Investigation of 49 Cases of Locally Advanced Nasopharyngeal Cancer Patients who were Given Neoadjuvant Docetaxel/Cisplatin Chemotherapy and Concomitant Chemoradiotherapy

Nasopharyngeal cancer (NPC) generally shows higher incidence in China, South-east Asia and some regions of the world. Being radioand chemo-sensitive, NPCs have higher prevalence in middle ages and occupy a special place among head and neck tumors. The aim of this study is to investigate the results of 49 locally advanced NPC patients who were given Docetaxel/cisplatin as neoadjuvant therapy and concomitant chemoradiotherapy. Our study included 49 locally advanced NPC patients who presented to our clinic between 2004 and 2011 and received two to three cures of neoadjuvant Docetaxel/Cisplatin therapy followed by concomitant chemoradiotherapy. Neoadjuvant chemotherapy scheme was docetaxel 75 mg /m2/day and cisplatin 75 mg/m2/day in three weeks. Median age of the patients was 50 years, and median follow-up period was 40.4 months. After concomitant chemotherapy of the patients, complete response was obtained in 47 (95.9%) patients and partial response in 2 (4.1%) patients. Average survival was found to be 78.3 months, and 3-year and 5-year survivals were 93% and 89% respectively. 8 of 49 patients developed recurrence. Average disease-free survival (DFS) was 67.4 months and 5-year DFS rate was 84%. Neoadjuvant chemotherapy in NPC increased disease-free survival rates, but failed to increase general survival. In our study, our patients disease-free survival and 5-year overall survival is quite good, these values have been found promising for the treatment of nasopharyngeal cancer. So this treatment regimen became a promising treatment choice due to its tolerable toxicity.

Metabolic Tumor Volume (MTV) and Maximum Standardized Uptake Value (SUVmax) as Predictive Factors in Locally Advanced Nasopharyngeal Cancer Treated With Definitive Chemoradiation Therapy

Metabolic Tumor Volume (MTV) and Maximum Standardized Uptake Value (SUVmax) as Predictive Factors in Locally Advanced Nasopharyngeal Cancer Treated With Definitive Chemoradiation Therapy

MRI to delineate the gross tumor volume of nasopharyngeal cancers: which sequences and planes should be used?

BackgroundMagnetic resonance imaging (MRI) has been found to be better than computed tomography for defining the extent of primary gross tumor volume (GTV) in advanced nasopharyngeal cancer. It is routinely applied for target delineation in planning radiotherapy. However, the specific MRI sequences/planes that should be used are unknown.MethodsTwelve patients with nasopharyngeal cancer underwent primary GTV evaluation with gadolinium-enhanced axial T1 weighted image (T1) and T2 weighted image (T2), coronal T1, and sagittal T1 sequences. Each sequence was registered with the planning computed tomography scans. Planning target volumes (PTVs) were derived by uniform expansions of the GTVs. The volumes encompassed by the various sequences/planes, and the volumes common to all sequences/planes, were compared quantitatively and anatomically to the volume delineated by the commonly used axial T1-based dataset.ResultsAddition of the axial T2 sequence increased the axial T1-based GTV by 12% on average (p = 0.004), and composite evaluations that included the coronal T1 and sagittal T1 planes increased the axial T1-based GTVs by 30% on average (p = 0.003). The axial T1-based PTVs were increased by 20% by the additional sequences (p = 0.04). Each sequence/plane added unique volume extensions. The GTVs common to all the T1 planes accounted for 38% of the total volumes of all the T1 planes. Anatomically, addition of the coronal and sagittal-based GTVs extended the axial T1-based GTV caudally and cranially, notably to the base of the skull.ConclusionsAdding MRI planes and sequences to the traditional axial T1 sequence yields significant quantitative and anatomically important extensions of the GTVs and PTVs. For accurate target delineation in nasopharyngeal cancer, we recommend that GTVs be outlined in all MRI sequences/planes and registered with the planning computed tomography scans.

Randomized phase III trial of concurrent chemoradiation with or without neoadjuvant gemcitabine, carboplatin, and paclitaxel in locally advanced nasopharyngeal cancer.

6003 Background: The role of neoadjuvant chemotherapy in addition to concurrent chemoradiation (CRT) in locally advanced nasopharyngeal cancer (NPC) is unclear. This trial investigates the overall ...

Comparison of concurrent chemoradiation therapy with 3-weekly versus weekly cisplatin in patients with locally advanced nasopharyngeal cancer: A multicenter randomized phase II noninferiority trial (KCSG-HN10-02).

6023 Background: Concurrent chemoradiation therapy (CCRT) with every 3 week schedule of cisplatin is the standard treatment for locally advanced nasopharyngeal carcinoma (NPC), but concerns have be...

Comparison of three different induction regimen in nasopharyngeal cancer: CF versus DC versus DCF.

6075 Background: The standard treatment of local advanced nasopharyngeal cancer is chemoradiotherapy. There is no enough data about the induction therapy. In this study we retrospectively examined ...

Factors Affecting Outcomes of Alternating Chemoradiotherapy for Nasopharyngeal Cancer

Nasopharyngeal cancer (NPC) is radiosensitive and chemosensitive. We evaluated the efficacy of alternating chemoradiotherapy in patients with advanced NPC. Alternating chemoradiotherapy was initiated in 30 patients with NPC, and 27 patients with cancer stages II (n = 6), III (n = 8), IVA (n = 9), and IVB (n = 4) were retrospectively analyzed. Chemotherapy was initially administered followed by radiotherapy, and chemotherapy, radiotherapy, and chemotherapy were alternately administered. Of the 27 patients, 22 patients received cisplatin (50 mg/m2/day, days 6 and 7) and 5-fluorouracil (5-FU; 800 mg/m2/day, days 1-5), whereas 5 patients received carboplatin (AUC 4-5, day 6) and 5-FU. Of the 27 patients, 19 (70%) received 3 chemotherapy courses. The total duration of alternating chemoradiotherapy was 81 to 101 days (median, 90 days). At a median follow-up of 53 months, the 5-year progression-free survival (PFS) was 71%. Multivariate analysis showed that weight loss and the number of chemotherapy courses had a significant effect on PFS. Alternating chemoradiotherapy led to similar or higher survival rates compared with concurrent chemoradiotherapy, which was characterized by good compliance and adaptable intensity.

Evaluation of hippocampus dose for patients undergoing intensity-modulated radiotherapy for nasopharyngeal carcinoma

To evaluate the dose received by the hippocampus among patients undergoing intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer. 10 patients with biopsy-proven, locally advanced nasopharyngeal cancer constituted the study population. The total prescribed dose to the planning target volume (PTV) was 70 Gy (D95%) delivered in 2.12-Gy daily fractions using IMRT. Using established anatomical guidelines, MRI co-registration and the assistance of a board-certified neuroradiologist, the right and left hippocampi were delineated on axial imaging from the CT scan obtained at simulation for each patient beginning at the most anterior portion of the lateral ventricle. IMRT treatment plans were generated without dose-volume constraints to the hippocampus. A range of dose-volume statistics was calculated. The mean hippocampus volume was 6.01 ± 2.61 cm(3). The mean V20 was 72.2%; V40 was 22.0%; V50 was 10.2%; and V60 was 5.5%. The average mean, minimum and maximum hippocampus doses were 30.27 Gy (range, 19.08-47.99 Gy); 17.54 Gy (range, 11.66-33.17 Gy); and 54.95 Gy (range, 35.59-75.57 Gy), respectively. The hippocampus received a maximum dose exceeding 70 Gy in 30% of cases. Our dosimetric analysis suggests that, for patients undergoing IMRT for nasopharyngeal cancer, the hippocampus routinely receives significantly high doses. The hippocampus receives a fair amount of incidental radiation during treatment for nasopharyngeal cancer. Given the importance of this structure with respect to memory and neurocognitive function, consideration should be given to identifying the hippocampus as a critical organ at risk in the IMRT optimization process.

Combining Drugs and Biologics to Treat Nasopharyngeal Cancer

Combining Drugs and Biologics to Treat Nasopharyngeal Cancer

The Predictive Value of Pretreatment 18-F-FDG-PET-CT in Locally Advanced Nasopharyngeal Cancer Patients Treated Definitively with Induction Chemotherapy Followed by Concurrent Chemo-Radiotherapy.

AimsThis study aimed to evaluate the role of pretreatment 18F-Fluorodeoxyglucose positron emission tomography (18F-FDG-PET-CT) as a predictor of disease-free survival (DFS), and overall survival (OS) in locally advanced nasopharyngeal carcinoma (LANPC) patients treated definitively with docetaxel-based induction chemotherapy followed by concurrent chemoradiation (CRT).Materials and methodsThis is a retrospective study approved by the institutional review board and included LANC patients treated definitively and consecutively between January 2008 and December 2012 with induction chemotherapy; docetaxel, cisplatin, and 5-flurouracil (TPF) followed by CRT utilizing weekly cisplatin. All patients had baseline pretreatment 18F-FDG-PET-CT. We studied the association between the baseline primary tumor maximum standardized uptake value (SUVmax) and the treatment outcomes; OS and DFS.ResultsThe study included 70 eligible LANPC patients. The 4-year OS and DFS rates were 86.7% and 78.6%, respectively. The median OS and DFS intervals were not reached. On a univariate analysis, the 4-years DFS was significantly higher in patients with pretreatment SUVmax <8 compared versus ≥ 8 (95% vs 57.7%, P=0.002). Furthermore, DFS was significantly correlated with pretreatment T stage (P=0.01), N stage (P=0.02), treatment response (P<0.001) and treatment breaks (P<0.001). On a multivariate analysis, the SUVmax category was the only factor correlated with 4-year DFS (Hazard ratio=10.2, 95% C I 1.3-116.8, P=0.035) but not OS (P=0.085).Disclosure statementThere is no actual or potential conflict of interest with the production and publication of this work. No author has a direct or indirect commercial financial incentive associated with the publication of this article.ConclusionThis study shows that the pretreatment primary tumor 18F-FDG-PET-CT SUVmax is a potential independent prognostic predictor of clinical outcomes in patients with LANC treated definitively with TPF induction chemotherapy followed by CRT. Further controlled clinical trials are worthwhile.

Low Expression of Excision Repair Cross-complementation Group-1 Protein Predicts Better Outcome in Patients with Locally Advanced Nasopharyngeal Cancer Treated with Concurrent Chemoradiotherapy

Low Expression of Excision Repair Cross-complementation Group-1 Protein Predicts Better Outcome in Patients with Locally Advanced Nasopharyngeal Cancer Treated with Concurrent Chemoradiotherapy

External Beam Radiation Therapy Followed by Stereotactic Radiosurgery for Primary Nasopharyngeal Carcinoma With Intracranial Extension

External Beam Radiation Therapy Followed by Stereotactic Radiosurgery for Primary Nasopharyngeal Carcinoma With Intracranial Extension

Neoadjuvant chemotherapy followed by concurrent chemoradiation for locoregionally advanced nasopharyngeal carcinoma

The authors studied the efficacy of neoadjuvant chemotherapy, consisting of a taxane, cisplatin, and 5-fluorouracil (5-FU) (the TPF regimen) followed by concurrent chemoradiation, in 2 separately designed and synchronously executed phase 2 trials for stage III and IVA/IVB nasopharyngeal cancer (NPC). Patients with newly diagnosed NPC were accrued to 2 trials, 1 for patients with stage III disease and the other for patients with IVA/IVB disease. All patients received TPF (docetaxel 75 mg/m(2), cisplatin 75 mg/m(2), and 5-FU 2500 mg/m(2) every 3 weeks for 3 cycles) followed by cisplatin 40 mg/m(2) per week concurrently with either 3-dimensional conformal radiation therapy or intensity-modulated radiation therapy. From January 2007 to July 2011, 52 eligible patients with stage III NPC and 64 eligible patients with nonmetastatic stage IV NPC were accrued. With a median follow-up of 32.9 months, the 3-year overall survival rates were 94.8% (95% confidence interval [CI], 87.6%-100%) and 90.2% (95% CI, 81.8%-98.6%) for the stage III NPC group and the IVA/IVB NPC group, respectively. The 3-year progression-free survival, distant metastasis-free survival, and local progression-free survival rates were 78.2% (95% CI, 64.6%-91.8%), 90.5% (95% CI, 79.7%-100%), and 93.9%(87.1%-100%), respectively, for patients with stage III NPC and 85.1% (95% CI, 75.1%-95.1%), 88% (95% CI, 78.6%-97.4%), and 100%, respectively, for patients with stage IVA/IVB NPC. The most common severe (grade 3/4) hematologic and nonhematologic adverse events were neutropenia (64 patients; 55.2%) and nausea/vomiting (23 patients; 19.8%). Neoadjuvant TPF followed by concurrent chemoradiation was well tolerated and produced encouraging outcomes in patients with locally advanced NPC in this hypothesis-generating study. The authors concluded that randomized controlled trials are warranted to definitively confirm this aggressive and potentially efficacious strategy.

Comorbidity and prognosis in head and neck cancers: Differences by subsite, stage, and human papillomavirus status

The prognostic utility of comorbidity on head and neck cancer may differ by subsite, stage, and human papillomavirus (HPV) status. We reviewed the medical records of 4953 patients with head and neck cancer for comorbidity (Charlson Comorbidity Index [CCI]), smoking, and alcohol history. Multivariate proportional hazards assessed the association of CCI with survival. HPV status was determined using p16 immunohistochemistry. After accounting for stage, higher CCI was associated with worse overall survival (OS) in nasopharyngeal (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.53-5.62), oropharyngeal (HR, 1.99; 95% CI, 1.63-2.43), and oral cavity cancers (HR, 1.54; 95% CI, 1.27-1.86). These associations were most prominent in the early stage oral cavity (HR, 2.11; 95% CI, 1.50-2.96) and laryngeal (HR, 1.87; 95% CI, 1.35-2.58) cancers, and in advanced stage oropharyngeal (HR, 2.23; 95% CI, 1.81-2.74) and nasopharyngeal (HR, 3.50; 95% CI, 1.76-6.97) cancers. CCI was independently prognostic even in the HPV-adjusted oropharyngeal cancers. Comorbidity was prognostic in subsets of nasopharyngeal, oropharyngeal, oral cavity, and laryngeal cancers. Comorbidity may be a partial surrogate for age and social habits.

Efficacy and safety of concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced nasopharyngeal cancers

Chemoradiation using cisplatin-based regimens has become the standard care in the treatment of nasopharyngeal cancers. The impact of taxanes as radiosensitizing agents with concurrent chemoradiation regimens is unknown. We retrospectively evaluated the efficacy and tolerability of weekly cisplatin + docetaxel combination with chemoradiation in locally advanced nasopharyngeal cancers. Forty-two patients with locally advanced nasopharyngeal cancers (59.5% stage IV, 23.3% stage III, and 16.7% stage II) were assessed retrospectively. Total radiation dose to the planning target volume of gross disease (primary and/or node) was 70 Gy/35 fractions, 5 fractions per week. Minimum doses of 60 Gy and 50 Gy were administered to planning target volume of elective high-risk and low-risk disease, respectively. Chemotherapy consisted of weekly cisplatin (20 mg/m(2)) + docetaxel (20 mg/m(2)) concurrently with radiotherapy. The median age of the patients was 46.5 years (range, 17-79). Objective response rate was 86%. The 4-year progression-free survival and overall survival were 65.4% and 91.3%, respectively. The most common grade 3 and 4 toxicities were mucositis (48%), nausea (22%), neutropenia (12%), dermatitis (5%), fatigue (5%) and weight loss (5%). Weekly cisplatin and docetaxel concurrent with radiotherapy for locally advanced nasopharyngeal cancers was found tolerable with a high efficacy.