Ting Jin

Long-term outcomes and failure patterns of patients with nasopharyngeal carcinoma staged by magnetic resonance imaging in intensity-modulated radiotherapy era: The Zhejiang Cancer Hospital's experience

PURPOSE To study and report the clinical outcomes and patterns of failure in the patients with nasopharyngeal carcinoma (NPC) staged by magnetic resonance imaging (MRI) and treated with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS From January 2007 to December 2011, 720 NPC patients without metastasis staged by MRI were treated with definitive IMRT at Zhejiang Cancer Hospital. The IMRT prescribed dose was 69 Gy to planning target volume (PTV) of gross disease in nasopharynx and 67.5 Gy to PTV of positive lymph nodes in 30 fractions, high risk, and low risk region PTV was 60 and 54 Gy in 30 fractions, respectively. The treatment outcomes and patterns of failure were observed. RESULTS Using the 7th edition of the American Joint Committee on Cancer staging system for NPC, the proportions of the 720 patients with Stages I, II, III, and IVa-b disease were 2.1% (15/720), 17.8% (128/720), 51.7% (372/720), and 28.5% (205/720), respectively. After the median follow-up period of 48 months (range: 3-89 months), a total of 146/720 (20.3%) patients had experienced failure: 37 (5.1%) at primary sites, 17 (2.4%) at regional sites, 79 (11.0%) at distant sites, and 13 (1.8%) at multiple sites. The 5-year overall survival, cancer-specific survival, disease-free survival, local relapse-free survival (LRFS), regional relapse-free survival, and distant metastasis (DM) free survival were 86.1%, 88.1%, 76.6%, 90.8%, 93.6%, and 87.2%, respectively. LRFS of T1 to T3 was all >90% and has no significant difference. In addition to N stage, T category, and neoadjuvant chemotherapy were independent predictors for DM in multivariate analysis. CONCLUSION Our long-term outcome of large NPC series supports the effectiveness of IMRT for excellent local-regional control though up to 20% patients would develop DM, which becomes the main pattern of failure. T4 disease remained difficult to be cured not only for local recurrence but distant failure. A taxane-based combination chemotherapy might be useful to reduce DM in the induction setting and worth further studying.

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.

Interim analysis of a prospective randomized non-inferiority trial of cisplatin and fluorouracil induction chemotherapy with or without docetaxel in nasopharyngeal carcinoma

In this study, we aim to compare the progression-free survival (PFS) rates and side effects of induction chemotherapy based on docetaxel, cisplatin and fluorouracil (TPF) versus cisplatin and fluorouracil (PF) in patients with locoregionally-advanced nasopharyngeal carcinoma who received subsequent chemoradiotherapy. We randomly assigned 278 patients with stage III or IV NPC (without distant metastases) to receive either TPF or PF induction chemotherapy, followed by cisplatin-based chemoradiotherapy every 3 weeks and intensity-modulated radiation therapy for 5 days per week. After a minimum of 2 years follow-up, a PFS benefit was observed for TPF compared to PF, though this difference was not statistically significant (84.5% vs. 77.9%, P = 0.380). Due to increased frequencies of grade 3 or 4 neutropenia and diarrhea, significantly more patients in the TPF group required treatment delays and dose modifications. Our findings suggest that PF induction chemotherapy has substantially better tolerance and compliance rates than TPF induction chemotherapy. However, the treatment efficacy of PF is not superior to TPF induction chemotherapy in patients with locoregionally-advanced NPC (ClinicalTrials.gov number, NCT01536223).

Endostar Combined with Gemcitabine and Cisplatin Chemotherapy for Patients with Metastatic Nasopharyngeal Carcinoma: an Update

OBJECTIVE: A previous phase-2 trial to assess the addition of Endostar to gemcitabine and cisplatin (GC) chemotherapy showed that it improves prognosis in metastatic nasopharyngeal carcinoma (M-NPC) but the study cohort was small. We wished to update that phase-2 trial by enrolling an additional 44 patients and to assess the benefit of Endostar+GC chemotherapy. METHODS: An analysis of 72 M-NPC patients treated between July 2010 and November 2016 was done. The treatment regimen was a combination of gemcitabine (1,000 mg/m2) on days 1 and 8, cisplatin (80 mg/m2) on day 1, and Endostar (15 mg/day) from day 1 to day 14 of a 21-day cycle for ≥2 cycles. The acute toxic effects and therapeutic efficacy were analyzed. RESULTS: The response rate was 77.8%. The median progression-free and overall survivals were 12 and 19.5 months, respectively. A total of 329 cycles of GC and 288 cycles of Endostar were delivered to 72 patients, with the median number of four (range, 2–10) cycles administered per patient. The main grade-3/4 hematologic toxicities were leukopenia (54.1%) and neutropenia (59.8%). The number of non-hematologic adverse events was minimal. The regimen was well-tolerated. CONCLUSIONS: Endostar+GC chemotherapy is an effective, well-tolerated regimen for M-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.

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.

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.

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.

6051Background: Distant metastasis is a poor prognostic factor in nasopharyngeal carcinoma (NPC). We aimed to evaluate the correlation between circulating lymphocyte subsets and clinical variables,...

Repeat biopsy of primary disease negatively affects the outcome of patients with nasopharyngeal cancer treated with definitive intensity-modified radiotherapy: a cohort analysis of 795 patients

OBJECTIVE To determine whether pretreatment repeat biopsy of nasopharynx is associated with an impaired outcome in nasopharyngeal carcinoma patients in an intensity-modified radiotherapy era. METHODS We performed a retrospective data review of the association between pretreatment nasopharyngeal biopsy and outcomes for all nasopharyngeal carcinoma patients treated at our center between January 2007 and December 2011. Of the 720 patients enrolled, 693 (96.3%) were diagnosed after initial biopsy and 27 (3.7%) after repeat biopsy. Five-year cancer-specific survival, disease-free survival and distant metastasis-free survival for the two groups were compared using univariate and multivariate analyses to evaluate the effects of repeat biopsy on the outcome. RESULTS Five-year estimated cancer-specific survival (75.9 vs. 88.5%, P= 0.045) and disease-free survival (63.3 vs. 77.1%, P= 0.041) were significantly poorer in the repeat biopsy group than the initial biopsy group. After adjustment for other prognostic factors (age, gender, T and N stage), pretreatment biopsy remained independently associated with poorer both 5-year cancer-specific survival and disease-free survival. The hazard ratios for cancer-specific survival and disease-free survival in the repeat biopsy group were 2.73 (95% confidence interval 1.09-6.82) and 2.22 (95% confidence interval 1.12-4.37) compared with the initial biopsy group (reference), respectively. The repeat biopsy group also had a higher risk of distant failure compared with the initial biopsy group (hazard ratio 2.82, 95% confidence interval 1.22-6.51, P= 0.015). CONCLUSION Pretreatment repeat biopsy of nasopharynx has a detrimental effect on survivals of nasopharyngeal carcinoma patients, which may be partly due to an increased frequency of distant metastasis.