Concurrent nimotuzumab and intensity-modulated radiotherapy for elderly patients with locally advanced nasopharyngeal carcinoma.

Because of the common physical condition, reduced organ function, and comorbidities, elderly patients with nasopharyngeal carcinoma (NPC) are often underrepresented in clinical trials. The optimal treatment of elderly patients with locally advanced NPC remains unclear. The purpose of this study was to evaluate the efficacy of concurrent nimotuzumab combined with intensity-modulated radiotherapy (IMRT) in elderly patients with locally advanced NPC. We conducted a single-arm, phase II trial for elderly patients with stage III-IVA NPC (according to UICC-American Joint Committee on Cancer TNM classification, 8th edition). All patients received concurrent nimotuzumab (200 mg/week, 1 week prior to IMRT) combined with IMRT. The primary end-point was complete response (CR) rate. The secondary end-points were survival, safety, and geriatric assessment. Between March 13, 2017 and November 12, 2018, 30 patients were enrolled. In total, 20 (66.7%) patients achieved CR, and objective response was observed in 30 (100.0%) patients 1 month after radiotherapy. The median follow-up time was 56.05 months (25th-75th percentile, 53.45-64.56 months). The 5-year locoregional relapse-free survival, distant metastasis-free survival, cancer-specific survival, disease-free survival, and overall survival were 89.4%, 86.4%, 85.9%, 76.5%, and 78.8%, respectively. Grade 3 mucositis occurred in 10 (33%) patients and grade 3 pneumonia in 3 (10%) patients. Concurrent nimotuzumab combined with IMRT is effective and well-tolerated for elderly patients with locally advanced NPC.

Nutritional Status and Its Association With Radiation-Induced Oral Mucositis in Patients With Nasopharyngeal Carcinoma During Radiotherapy: A Prospective Study.

BACKGROUND AND AIMS: Malnutrition is a concern in patients with nasopharyngeal carcinoma (NPC) during chemoradiotherapy (CRT)/radiotherapy (RT), which is considered to be related with radiation-induced oral mucositis (ROM). The study aimed to evaluate the nutritional status of NPC patients during RT and investigate its association with ROM. METHODS: A prospective study was conducted in NPC patients. Patients were divided into three subgroups (mild, moderate, and severe groups) based on the duration of severe ROM (≥ grade 3). Body weight, body mass index (BMI), albumin, prealbumin, NRS2002, and ROM grade were assessed on a weekly basis before and during CRT/RT. The statistical analysis was performed in the overall group and between three subgroups. RESULTS: A total of 176 patients were included. In the overall group, body weight and BMI kept decreasing since week 1 of RT, and NRS2002 score and ROM grade increased (p < 0.001). NRS2002 score and prealbumin levels were significantly different between each subgroup (p ≤ 0.046). Significant differences were observed in the proportion of patients receiving enteral nutrition, duration of parenteral nutrition, and total calories provided by nutritional support among three subgroups (p = 0.045-0.001). CONCLUSIONS: Malnutrition occurred early in NPC patients and worsened continuously during RT. ROM was strongly associated with nutritional status. Nutritional support should be provided at the start of RT, especially in patients at high-risk of severe ROM.

Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial.

To report long-term results of a randomized controlled trial that compared cisplatin/fluorouracil/docetaxel (TPF) induction chemotherapy (IC) plus concurrent chemoradiotherapy (CCRT) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma (NPC). Patients with stage III-IVB (except T3-4 N0) NPC were randomly assigned to receive IC plus CCRT (n = 241) or CCRT alone (n = 239). IC included three cycles of docetaxel (60 mg/m2 d1), cisplatin (60 mg/m2 d1), and fluorouracil (600 mg/m2 /d civ d1-5) every 3 weeks. Patients from both groups received intensity-modulated radiotherapy concurrently with three cycles of 100 mg/m2 cisplatin every 3 weeks. After a median follow-up of 71.5 months, the IC plus CCRT group showed significantly better 5-year failure-free survival (FFS, 77.4% vs. 66.4%, p = 0.019), overall survival (OS, 85.6% vs. 77.7%, p = 0.042), distant failure-free survival (88% vs. 79.8%, p = 0.030), and locoregional failure-free survival (90.7% vs. 83.8%, p = 0.044) compared to the CCRT alone group. Post hoc subgroup analyses revealed that beneficial effects on FFS were primarily observed in patients with N1, stage IVA, pretreatment lactate dehydrogenase ≥170 U/l, or pretreatment plasma Epstein-Barr virus DNA ≥6000 copies/mL. Two nomograms were further developed to predict the potential FFS and OS benefit of TPF IC. The incidence of grade 3 or 4 late toxicities was 8.8% (21/239) in the IC plus CCRT group and 9.2% (22/238) in the CCRT alone group. Long-term follow-up confirmed that TPF IC plus CCRT significantly improved survival in locoregionally advanced NPC with no marked increase in late toxicities and could be an option of treatment for these patients.

Paranasal Sinus Invasion in Nasopharyngeal Carcinoma after Intensity-Modulated Radiotherapy.

PURPOSE: The aim of this study is to evaluate the prognostic significance of paranasal sinus invasion for nasopharyngeal carcinoma (NPC) and its suitable position in the T classification. MATERIALS AND METHODS: The magnetic resonance imaging (MRI) scans of 695 patients with previously untreated, biopsy-proven, non-metastatic NPC that was treated with intensity-modulated radiotherapy (IMRT) were reviewed retrospectively. RESULTS: The incidence of paranasal sinus invasion was 39.4% (274 of 695 patients). Multivariate analysis showed that paranasal sinus invasion was an independent negative prognostic factor for local failure-free survival (LFFS) (p < 0.05). According to the eighth American Joint Committee on Cancer (AJCC) staging system, 275 patients were classified as T3 classification. Of these, 78 patients (28.4%) developed paranasal sinus invasion (T3b) and 197 (71.6%) didn't (T3a). The estimated 5-year LFFS and overall survival (OS) rates for the patients with T3b and T3a classification were 88.6% versus 95.0% (p=0.047), and 84.5% versus 93.3% (p=0.183), respectively. The estimated 5-year LFFS and OS rates for the patientswith T4 classificationwere 89.5% and 83.2%,whichwere similarwith the outcomes of patients with T3b classification. CONCLUSION: MRI-determined paranasal sinus invasion is an independent prognostic factor of NPC treated by IMRT. Paranasal sinus invasion is recommended to classify as T4 classification in the 8th AJCC staging system for NPC.

Locoregional extension and patterns of failure for nasopharyngeal carcinoma with intracranial extension.

OBJECTIVE: To evaluate the locoregional extension and patterns of failure for nasopharyngeal carcinoma (NPC) with intracranial extension to improve clinical target volume (CTV) delineation. PATIENTS AND METHODS: A total of 205 NPC patients with intracranial extension by magnetic resonance imaging (MRI) were retrospectively reviewed. RESULTS: According to the cumulative incidence rates of tumor invasion, we initially classified anatomic sites surrounding the nasopharynx into three risk grades: high risk (≥35%), medium risk (≥10-35%), and low risk (<10%). It was concluded that the anatomic sites at high risk of tumor invasion were the middle/posterior skull base and the anatomic sites adjacent to the nasopharynx. The rate of lymph node (LN) metastasis was 90.2% (185/205). Retropharyngeal region (RP) and level IIb were the most frequently involved regions. Skip metastasis occurred in only 1.6% (3/185). At their last follow-up visit, 53 patients (25.9%) had developed treatment failure. Of the 18 local failures, 12 were considered in-field failure; the other 5 were marginal; one of the patients had outside-field failure. Among the 5 patients with marginal failures, 4 occurred mainly intracranially, and 1 occurred in the floor and the left lateral wall of the nasopharynx. Of the 11 regional failures, 10 were considered in-field failures and most of them (8/10) occurred in the unilateral upper neck. CONCLUSION: For NPC with intracranial extension, primary disease and regional LN spread follow an orderly pattern and LN skipping was unusual. Clinical target volume reduction may be feasible for selected patients.

Neoadjuvant chemotherapy with different dose regimens of docetaxel, cisplatin and fluorouracil (TPF) for locoregionally advanced nasopharyngeal carcinoma: a retrospective study.

OBJECTIVE: Compare high- vs. low-dose TPF neoadjuvant chemotherapy with chemoradiotherapy in Chinese patients with locoregionally advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Retrospective analysis of 210 stage III/IV NPC patients treated between April 1, 2012 and April 1, 2014; 138 received three cycles of high-dose TPF (H-TPF) every 3 weeks at Zhejiang Cancer Hospital and 72, three cycles of low-dose TPF (L-TPF) every 3 weeks at Sun Yat-Sen University Cancer Center. H-TPF was docetaxel (75 mg/m2; 1 h infusion), cisplatin (75 mg/m2; 0.5-3 h), then 5-fluorouracil (600 mg/m2/day; 4 days). L-TPF was docetaxel (60 mg/m2), cisplatin (65 mg/m2), then 5-fluorouracil (550 mg/m2/day; 5 days). All patients received chemoradiotherapy. RESULTS: During neoadjuvant chemotherapy, treatment delays were more frequent for H-TPF than L-TPF (33.3% vs. 19.4%; P = 0.034). During chemoradiotherapy, grade III-IV anemia, thrombocytopenia and neutropenia were more common for H-TPF than L-TPF (P < 0.001, P < 0.001, P = 0.048). Fewer patients in the H-TPF group finished two cycles of concurrent chemotherapy (81.2% vs. 100%, P < 0.001). Three-year PFS (84.5% vs. 80.6%, P = 0.484) and OS (91.1% vs. 93.5%, P = 0.542) were not significantly different between H-TPF and L-TPF. CONCLUSIONS: L-TPF neoadjuvant chemotherapy has substantially better tolerance and compliance rates and similar treatment efficacy to H-TPF neoadjuvant chemotherapy in locoregionally-advanced NPC.

The C-reactive Protein/Albumin Ratio Is an independent Prognostic Factor for Overall Survival in Patients with Nasopharyngeal Carcinoma Receiving Intensity-Modulated Radiotherapy.

This study aims to investigate the prognostic value of the C-reactive protein/albumin (CRP/ALB) ratio in nasopharyngeal carcinoma (NPC) in the intensity-modulated radiotherapy (IMRT) era. A total of 719 patients with NPC treated between January 2007 and December 2012 were retrospectively reviewed. Serum albumin and CRP levels were measured before treatment. The associations between the CRP/ALB ratio and clinicopathological parameters were analyzed. Multivariate analyses using the Cox proportional hazards model were performed to identify significant prognostic factors associated with overall survival (OS). The prognostic value of the CRP/ALB ratio was determined using receiver operating characteristic (ROC) curve analysis. The optimal CRP/ALB ratio cutoff value was 0.141. High CRP/ALB ratio was significantly associated with older age (P < 0.001), more advanced T category (P < 0.001) and advanced TNM stage (P = 0.024). Patients with an elevated CRP/ALB ratio (≥ 0.141) had poorer OS than those with a CRP/ALB ratio < 0.141 (5-year OS rates: 91.9% vs. 78.1%; P < 0.001). Multivariate analysis suggested clinical T category [hazard ratio (HR) 2.284; 95% confidence interval (CI), 1.429-3.652; P = 0.001]; clinical N category (HR 1.575; 95% CI, 1.007-2.464; P = 0.047) and CRP/ALB ratio (HR 2.173; 95% CI, 1.128-3.059; P = 0.015) were independently associated with OS. In conclusion, pretreatment CRP/ALB ratio is an objective biomarker with significant prognostic value for OS in NPC. The CRP/ALB ratio can enhance conventional TNM staging to stratify patients and may help facilitate individualized treatment of high-risk cases.

Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial.

BACKGROUND: The value of adding cisplatin, fluorouracil, and docetaxel (TPF) induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma is unclear. We aimed to compare TPF induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone in a suitably powered trial. METHODS: We did an open-label, phase 3, multicentre, randomised controlled trial at ten institutions in China. Patients with previously untreated, stage III-IVB (except T3-4N0) nasopharyngeal carcinoma, aged 18-59 years without severe comorbidities were enrolled. Eligible patients were randomly assigned (1:1) to receive induction chemotherapy plus concurrent chemoradiotherapy or concurrent chemoradiotherapy alone (three cycles of 100 mg/m2 cisplatin every 3 weeks, concurrently with intensity-modulated radiotherapy). Induction chemotherapy was three cycles of intravenous docetaxel (60 mg/m2 on day 1), intravenous cisplatin (60 mg/m2 on day 1), and continuous intravenous fluorouracil (600 mg/m2 per day from day 1 to day 5) every 3 weeks before concurrent chemoradiotherapy. Randomisation was by a computer-generated random number code with a block size of four, stratified by treatment centre and disease stage (III or IV). Treatment allocation was not masked. The primary endpoint was failure-free survival calculated from randomisation to locoregional failure, distant failure, or death from any cause; required sample size was 476 patients (238 per group). We did efficacy analyses in our intention-to-treat population. The follow-up is ongoing; in this report, we present the 3-year survival results and acute toxic effects. This trial is registered with ClinicalTrials.gov, number NCT01245959. FINDINGS: Between March 1, 2011, and Aug 22, 2013, 241 patients were assigned to induction chemotherapy plus concurrent chemoradiotherapy and 239 to concurrent chemoradiotherapy alone. After a median follow-up of 45 months (IQR 38-49), 3-year failure-free survival was 80% (95% CI 75-85) in the induction chemotherapy plus concurrent chemoradiotherapy group and 72% (66-78) in the concurrent chemoradiotherapy alone group (hazard ratio 0·68, 95% CI 0·48-0·97; p=0·034). The most common grade 3 or 4 adverse events during treatment in the 239 patients in the induction chemotherapy plus concurrent chemoradiotherapy group versus the 238 patients in concurrent chemoradiotherapy alone group were neutropenia (101 [42%] vs 17 [7%]), leucopenia (98 [41%] vs 41 [17%]), and stomatitis (98 [41%] vs 84 [35%]). INTERPRETATION: Addition of TPF induction chemotherapy to concurrent chemoradiotherapy significantly improved failure-free survival in locoregionally advanced nasopharyngeal carcinoma with acceptable toxicity. Long-term follow-up is required to determine long-term efficacy and toxicities. FUNDING: Shenzhen Main Luck Pharmaceuticals Inc, Sun Yat-sen University Clinical Research 5010 Program (2007037), National Science and Technology Pillar Program during the Twelfth Five-year Plan Period (2014BAI09B10), Health & Medical Collaborative Innovation Project of Guangzhou City (201400000001), Planned Science and Technology Project of Guangdong Province (2013B020400004), and The National Key Research and Development Program of China (2016YFC0902000).

A prognostic model combining CD4/CD8 ratio and N stage predicts the risk of distant metastasis for patients with nasopharyngeal carcinoma treated by intensity modulated radiotherapy.

This study aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables, and design an effective prognostic model for distant metastasis-free survival (DMFS) in NPC. In this study, subsets of circulating lymphocytes were determined in 719 non-metastatic NPC patients before treatment. Overall survival and DMFS was monitored. Significant prognostic factors were identified using univariate and multivariate analyses. Results showed that the percentage of CD19+ lymphocytes correlated negatively with TNM stage (r = -0.082, P = 0.028). Patients with higher CD4/CD8 ratios (≥ 1.77) showed better 5-year DMFS than patients with lower ratios (91.9% vs. 85.4%, P < 0.001). Multivariate analysis revealed that CD4/CD8 ratio (HR, 0.450; 95% confidence interval [CI], 0.266-0.760; P = 0.003) and N classification (HR, 2.294; 95% CI, 1.370-3.839; P = 0.002) were independently prognostic factors for DMFS. The prognostic N-R model was developed and divided patients into three groups: (1) low-risk (early N stage and CD4/CD8 ratio ≥ 1.77); (2) intermediate-risk (advanced N stage or CD4/CD8 ratio < 1.77) and (3) high-risk (advanced N stage and CD4/CD8 ratio < 1.77) of distant metastasis. In conclusion our prognostic model, based on clinical N stage and CD4/CD8 ratio, may predict the risk of distant metastasis, allowing individualized treatment for NPC.

Gastric adenocarcinoma with thyroid metastasis: A case study and literature review.

Previously, cases of metastatic thyroid cancer were only identified following mortality, by autopsy studies. Incidence of this disease is currently estimated to be between 0.5% in all malignant tumors and 24% in all patients based on autopsy studies. Metastatic thyroid cancer is associated with poor prognosis. In the present study, a 58-year-old male presented with a cervical mass. Subtotal gastrectomy and D2 lymph node dissection identified a poorly differentiated gastric adenocarcinoma. Following this, fine needle aspiration was performed, revealing that the thyroid tumor cells were similar to gastric tumor cells, indicative of metastasis from this organ of origin. In addition, immunohistochemical analysis was consistent with this diagnosis. Palliative radiotherapy of the thyroid mass was performed. At manuscript submission, the patient remained alive.

Prognostic role of serum cytokines in patients with nasopharyngeal carcinoma.

BACKGROUND: Th1/Th2 cytokine network imbalance plays a major role in cancer development and progression. In this study, we aim to evaluate the relationship between those cytokines and clinical outcome in patients with nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: The concentrations of Th1 cytokines (IL-2, TNF-α, IFN-γ) and Th2 cytokines (IL-4, IL-5, IL-10) in the serum were examined by Cytometric Bead Array in a total of 80 nasopharyngeal carcinoma patients pre and post treatment. Associations of those cytokines with clinical pathological factors, treatment response, and overall survival were analyzed. RESULTS: Pretreatment serum levels of IL-2 and TNF-α were closely associated with overall survival. Compared to patients with low IL-2 expression, those with high expression had less risk of death (hazard ratio (HR) = 0.31, 95% confidence interval (CI) 0.13-0.75, p = 0.009). In contrast, TNF-α showed opposite effects on overall survival in patients with NPC. Patients with high TNF-α expression had a more than 2-fold increase in risk of death than those with low TNF-α (HR = 2.66, 95% CI 1.04-6.78, p = 0.041). All HRs were adjusted for age, sex, stage, histology, and treatment. Kaplan-Meier survival analysis showed similar survival differences between the 2 groups. CONCLUSION: Lower serum IL-2 or elevated serum TNF-α concentrations predict an unfavorable prognosis for patients with NPC.