Efficacy and safety of cadonilimab in previously treated recurrent or metastatic nasopharyngeal carcinoma(COMPASSION-06): A phase II multicenter study.

OBJECTIVE: This study was designed to assess the efficacy and safety of cadonilimab monotherapy, a first-in-class, bi-specific PD-1/CTLA-4 antibody, in patients with previously treated recurrent or metastatic nasopharyngeal carcinoma (R/M-NPC). PATIENTS AND METHODS: This multicenter, open-label, single-arm, phase II clinical trial enrolled patients with R/M-NPC who had failed first-line platinum-based chemotherapy and second-line single agent or combined chemotherapy, and immunotherapy-naive. Patients received cadonilimab for 6 mg/kg once every 2 weeks (Q2W). The primary endpoint was objective response rate (ORR) in full analysis set (FAS) assessed by investigators according to RECIST v.1.1. The secondary endpoint included progression-free survival (PFS), overall survival (OS), duration of response (DoR), time to response (TTR) and safety. RESULTS: A total of 23 patients were assessed. The median time from first dose to data cutoff was 16.56 (range, 0.8-25.2) months. ORR was 26.1 % (95 %CI:10.2-48.4). The ORR were 44.4 % (95 %CI: 13.7-78.8) and 14.3 % (95 %CI:1.8-42.8) in patients with tumor PD-L1 expression ≥50 % and <50 %, respectively. ORR was achieved in 40.0 % (95 %CI:12.2-73.8) of patients with EBV-DNA level <4000 IU/ml (n = 10) and 15.4 % (95 %CI:1.9-45.4) of those with ≥4000 IU/ml. The median PFS was 3.71 months (95 %CI: 1.84-9.30). respectively. Median OS was not reached, and the 12-month OS rate was 79.7 % (95 % CI:54.5-91.9). Only two patients (8.3 %) experienced Grade ≥3 treatment-related adverse events (TRAEs) with hypothyroidism (30.4 %), rash (21.7 %) and pruritus (21.7 %) being the most prevalent TRAEs. CONCLUSION: Cadonilimab monotherapy demonstrated a promising efficacy and manageable toxicity in patients with previously treated R-M/NPC and provide an efficacious salvage treatment option.

MRI-based deep learning model predicts distant metastasis and chemotherapy benefit in stage II nasopharyngeal carcinoma.

Chemotherapy remains controversial for stage II nasopharyngeal carcinoma because of its considerable prognostic heterogeneity. We aimed to develop an MRI-based deep learning model for predicting distant metastasis and assessing chemotherapy efficacy in stage II nasopharyngeal carcinoma. This multicenter retrospective study enrolled 1072 patients from three Chinese centers for training (Center 1, n = 575) and external validation (Centers 2 and 3, n = 497). The deep learning model significantly predicted the risk of distant metastases for stage II nasopharyngeal carcinoma and was validated in the external validation cohort. In addition, the deep learning model outperformed the clinical and radiomics models in terms of predictive performance. Furthermore, the deep learning model facilitates the identification of high-risk patients who could benefit from chemotherapy, providing useful additional information for individualized treatment decisions.

Comparison the acute toxicity of two different induction chemotherapy schedules with cisplatin and fluorouracil in nasopharyngeal carcinoma patients.

PURPOSE: To compare the acute toxicity of two different induction chemotherapy (IndCT) regimen followed by the same IMRT in patients with advanced nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: From July 2015 to December 2016, 110 NPC patients with stage III-IV diseases were prospectively randomized to receive either a conventional triweekly cisplatin + 5-fluorouracil (PF) for 3 cycles or weekly P-F for 10 doses, followed by the same IMRT to both arms. The primary endpoints of this study were grade 3/4 and any grade acute toxicities during IndCT period. The secondary endpoints included tumor response and various survivals. RESULTS: Baseline patient characteristics were comparable in both groups. Patients who received weekly P-F experienced significant reduction of grade 3/4 acute toxicities, including neutropenia (12.7% vs. 40.0%, P = 0.0012), anorexia (0% vs. 14.6%, P = 0.0059), mucositis (0% vs. 14.6%, P = 0.0059), and hyponatremia (0% vs. 16.4%, P = 0.0027), compared with the triweekly PF group, resulting in fewer IndCT interruptions (1.8% vs. 16.4%, P = 0.0203), emergency room visits (0% vs. 12.7%, P = 0.0128), and additional hospitalizations (0% vs. 9.1%, P = 0.0568). The acute toxicities during IMRT period were similar. Weekly P-F arm had higher complete response rates (83.6% vs. 61.8%, P = 0.0152) and lower relapse rates (16.4% vs. 33.3%, P = 0.0402) after a median follow-up of 67 months. Kaplan-Meier survival analyses revealed a better trend of locoregional failure-free (P = 0.0892), distant metastasis failure-free (P = 0.0775), and progression-free (P = 0.0709) survivals, favoring the weekly P-F arm. CONCLUSION: IndCT of weekly schedule does reduce acute toxicities without compromised tumor response and survivals.

The role of radiologic extranodal extension in predicting prognosis and chemotherapy benefit for T1-2 N1 nasopharyngeal carcinoma: A multicenter retrospective study.

BACKGROUND AND PURPOSE: This multicenter retrospective study aimed to investigated the prognostic value of unequivocal radiologic extranodal extension (rENE) and the efficacy of chemotherapy for stage T1-2 N1 nasopharyngeal carcinoma (NPC) in the IMRT era. MATERIALS AND METHODS: We included 1,082 patients treated in 2005-2017 from three centers. rENE was recorded as G1 (coalescent nodal mass comprising ≥ 2 inseparable nodes) or G2 (invading beyond perinodal fat to frankly infiltrate adjacent structures). Multivariable analysis (MVA) evaluated the prognostic value of rENE. The value of chemotherapy was assessed in rENE-positive (rENE + ) and rENE-negative (rENE - ) subset separately. RESULTS: Centers 1, 2, and 3 had 139/515 (27.0 %), 100/365 (27.4 %), and 43/202 (21.3 %) cN + patients with rENE, respectively. Compared to rENE-, rENE + patients had a worse distant metastasis-free survival (DMFS) and overall survival (OS) (all p < 0.001). MVA confirmed the prognostic of both G1-rENE and G2-rENE for distant metastasis [G1: hazard ratio (HR): 2.933, G2: HR: 6.942, all p < 0.001] and death (G1: HR: 1.587, p = 0.040; G2: HR: 6.162, p < 0.001). There was no significant difference for DMFS and OS between chemo-radiotherapy and radiotherapy alone in rENE + and rENE - groups (all p > 0.1). However, rENE + patients with a cumulative cisplatin/nedaplatin dose (CCND) of > 160 mg/m2 had an improved DMFS (p = 0.033) but no OS (p = 0.197). CONCLUSION: Unequivocal rENE is prognostic in patients with T1-2 N1 NPC. Addition of chemotherapy to radiotherapy did not affect DMFS and OS in rENE - patients. Chemotherapy with a CCND of > 160 mg/m2 improved DMFS in rENE + patients.

Comparison of radiotherapy combined with nimotuzumab vs. chemoradiotherapy for locally recurrent nasopharyngeal carcinoma.

BACKGROUND: The present study compared the effectiveness and toxicity of two treatment modalities, namely radiotherapy combined with nimotuzumab (N) and chemoradiotherapy (CRT) in patients with locally recurrent nasopharyngeal carcinoma (LR-NPC). METHODS: Patients with LR-NPC who were treated with radiotherapy were retrospectively enrolled from January 2015 to December 2018. The treatment included radiotherapy combined with N or platinum-based induction chemotherapy and/or concurrent chemotherapy. The comparison of survival and toxicity between the two treatment modalities was evaluated using the log-rank and chi-squared tests. Overall survival (OS) was the primary endpoint. RESULTS: A total of 87 patients were included, of whom 32 and 55 were divided into the N group and the CRT group, respectively. No significant differences were noted in the survival rate between the N and the CRT groups (4-year OS rates, 37.1% vs. 40.7%, respectively; P = 0.735). Mild to moderate acute complications were common during the radiation period and mainly included mucositis and xerostomia. The majority of the acute toxic reactions were tolerated well. A total of 48 patients (55.2%) demonstrated late radiation injuries of grade ≥ 3, including 12 patients (37.5%) in the N group and 36 patients (66.5%) in the CRT group. The CRT group exhibited significantly higher incidence of severe late radiation injuries compared with that of the N group (P = 0.011). CONCLUSION: Radiotherapy combined with N did not appear to enhance treatment efficacy compared with CRT in patients with LR-NPC. However, radiotherapy combined with N may be superior to CRT due to its lower incidence of acute and late toxicities. Further studies are required to confirm the current findings.

The Chinese Society of Clinical Oncology (CSCO) clinical guidelines for the diagnosis and treatment of nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi-disciplinary team comprising of experts from all sub-specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence-based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow-up of NPC, which aim to improve the management of NPC.

Autocrine INSL5 promotes tumor progression and glycolysis via activation of STAT5 signaling.

Metabolic reprogramming plays important roles in development and progression of nasopharyngeal carcinoma (NPC), but the underlying mechanism has not been completely defined. In this work, we found INSL5 was elevated in NPC tumor tissue and the plasma of NPC patients. Plasma INSL5 could serve as a novel diagnostic marker for NPC, especially for serum VCA-IgA-negative patients. Moreover, higher plasma INSL5 level was associated with poor disease outcome. Functionally, INSL5 overexpression increased, whereas knockdown of its receptor GPCR142 or inhibition of INSL5 reduced cell proliferation, colony formation, and cell invasion in vitro and tumorigenicity in vivo. Mechanistically, INSL5 enhanced phosphorylation and nuclear translocation of STAT5 and promoted glycolytic gene expression, leading to induced glycolysis in cancer cells. Pharmaceutical inhibition of glycolysis by 2-DG or blockade of INSL5 by a neutralizing antibody reversed INSL5-induced proliferation and invasion, indicating that INSL5 can be a potential therapeutic target in NPC. In conclusion, INSL5 enhances NPC progression by regulating cancer cell metabolic reprogramming and is a potential diagnostic and prognostic marker as well as a therapeutic target for NPC.

Potential diagnostic value of PD-1 in peripheral blood mononuclear cells of postmenopausal osteoporosis patients.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is an estrogen deficiency-induced skeletal disorder. Bone mineral density (BMD) testing is the gold standard for diagnosing osteoporosis. However, its sensitivity for fracture risk assessment is low. Programmed cell death protein 1 (PD-1) is a key immune checkpoint molecule implicated in the pathophysiology of bone remodeling, but its role in osteoporosis has not yet been explored. Thus, this study aimed to assess the expression and diagnostic utility of PD-1 in PMOP. METHODS: A total of 56 patients with PMOP and 37 postmenopausal healthy controls (NC) were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient centrifugation, and PD-1 expression was measured by quantitative polymerase chain reaction (qPCR). Pearson's correlation test was performed to explore the associations between PD-1 level and clinical variables, while receiver operating characteristic (ROC) curve analysis was used to evaluate the potential diagnostic value of PD-1 in patients with PMOP. RESULTS: We found that PD-1 level was significantly upregulated in the PBMCs of PMOP patients than those of NC (P = .016). PD-1 expression was positively correlated with C-reactive protein (CRP) levels. ROC curve analysis showed that PD-1 had certain diagnostic value for PMOP (area under the curve = 0.65, standard error = 0.06, 95% confidence interval [0.53,0.76], P = .016), with a sensitivity and specificity of 44.64% and 81.08%, respectively. CONCLUSION: Programmed cell death protein 1 is significantly upregulated in the PBMCs of PMOP patients and has certain diagnostic value for PMOP.

Epstein-Barr virus-coded miR-BART13 promotes nasopharyngeal carcinoma cell growth and metastasis via targeting of the NKIRAS2/NF-κB pathway.

Based on analysis of Epstein-Barr virus (EBV) BART microRNA expression profiles, we previously reported that EBV-encoded miR-BART13 is upregulated in nasopharyngeal carcinoma (NPC) plasma specimens. However, the effects and molecular mechanisms of miR-BART13 in NPC remain largely unknown. We found that miR-BART13 was significantly upregulated in NPC tissue specimens. Ectopic expression of miR-BART13 promoted NPC cell proliferation, epithelial mesenchymal transition, and metastasis in vitro, and facilitated xenograft tumor growth and lung metastasis in vivo. Molecularly, NF-κB inhibitor interacting Ras-like 2 (NKIRAS2), a negative regulator of the NF-κB signaling, was identified to be a direct target of miR-BART13 in NPC cells, and NKIRAS2 mRNA and protein expression was inversely correlated with miR-BART13 in NPC tissues, respecitvely. Furthermore, the NF-κB signaling pathway was activated by miR-BART13. By rescued experiments, reconstitution of NKIRAS2 expression abrogated all the phenotypes upregulated by miR-BART13, and attenuated activity of NF-κB signaling pathway activated by miR-BART13 in NPC cells. Our findings indicated the newly identified miR-BART13/NKIRAS2/NF-κB signaling axis may provide further insights into better understanding of NPC initiation and development, and targeting of this pathway could be further studied as a therapeutic strategy for NPC patients.

Systemic immune-inflammation index as a prognostic marker in patients with newly diagnosed metastatic nasopharyngeal carcinoma: a propensity score-matched study.

BACKGROUND: Systemic immune-inflammation index (SII) is significantly associated with poor survival in variety of cancers. However, SII has not yet been investigated in patients with newly diagnosed metastatic nasopharyngeal carcinoma (mNPC). Thus, our aim is to explore the role of SII in metastatic Nasopharyngeal Carcinoma. METHODS: Two hundred and forty-three patients with newly diagnosed mNPC were retrospectively enrolled. The Kaplan-Meier analysis and Cox regression analysis was performed to evaluate the prognostic value of SII in overall survival (OS) and progression-free survival (PFS). Heterogeneity of factors was balanced by using propensity score-matched (PSM) analysis (1:1 for high SII versus low SII). RESULTS: Kaplan-Meier analysis showed that patients with high SII were associated with poor median OS (18.0 vs. 36.0 m, P<0.001) and PFS (10.0 vs. 22.0 m, P<0.001) in mNPC. The Cox regression analysis suggested that high SII was a prognostic factor for OS (HR 1.75, 95% CI: 1.22-2.52, P=0.001) and PFS (HR 1.69, 95% CI: 1.22-2.35, P=0.002). PSM analysis still confirmed that SII was an independent marker for OS (HR 1.86, 95% CI: 1.22-2.83, P=0.004) and PFS (HR 1.84, 95% CI: 1.23-2.77, P=0.003). CONCLUSIONS: SII is an independent prognostic biomarker for poor OS and PFS in patients with newly diagnosed mNPC and might be a promising tool for guiding treatment strategy decisions.

Prognostic nomogram for refining the prognostication of the proposed 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy.

BACKGROUND: The objective of this study was to develop a nomogram for refining prognostication for patients with nondisseminated nasopharyngeal cancer (NPC) staged with the proposed 8th edition of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) staging system. METHODS: Consecutive patients who had been investigated with magnetic resonance imaging, staged with the proposed 8th edition of the AJCC/UICC staging system, and irradiated with intensity-modulated radiotherapy from June 2005 to December 2010 were analyzed. A cohort of 1197 patients treated at Fujian Provincial Cancer Hospital was used as the training set, and the results were validated with 412 patients from Pamela Youde Nethersole Eastern Hospital. Cox regression analyses were performed to identify significant prognostic factors for developing a nomogram to predict overall survival (OS). The discriminative ability was assessed with the concordance index (c-index). A recursive partitioning algorithm was applied to the survival scores of the combined set to categorize the patients into 3 risk groups. RESULTS: A multivariate analysis showed that age, gross primary tumor volume, and lactate dehydrogenase were independent prognostic factors for OS in addition to the stage group. The OS nomogram based on all these factors had a statistically higher bias-corrected c-index than prognostication based on the stage group alone (0.712 vs 0.622, P <.01). These results were consistent for both the training cohort and the validation cohort. Patients with <135 points were categorized as low-risk, patients with 135 to <160 points were categorized as intermediate-risk, and patients with ≥160 points were categorized as high-risk. Their 5-year OS rates were 92%, 84%, and 58%, respectively. CONCLUSIONS: The proposed nomogram could improve prognostication in comparison with the TNM stage group. This could aid in risk stratification for individual NPC patients. Cancer 2016;122:3307-3315. © 2016 American Cancer Society.

High-density lipoprotein cholesterol as a predictor of poor survival in patients with nasopharyngeal carcinoma.

PURPOSE: We aimed to assess the prognostic value of pretreatment high density lipoprotein cholesterol (HDL-C) levels in patients with nasopharyngeal carcinoma (NPC) and investigate the possible biological effects of these lipoproteins on NPC cells in vitro. EXPERIMENTAL DESIGN: We examined the prognostic value of pretreatment HDL-C levels in 2443 patients with non-metastatic NPC from three independent institutions. The Cox proportional hazard model and log-rank test were used to analyze the correlation between HDL-C levels and overall survival (OS). Cell growth, colony formation, and apoptotic assays were used to determine the biological functions of HDL on NPC cells in vitro. All of the statistical tests were two-sided. RESULTS: OS was decreased in patients with high pretreatment HDL-C levels compared with those with low HDL-C levels (P < 0.05). Similarly, a decreased OS was noted in advanced stage (stage III-IV), NPC patients with high pretreatment HDL-C levels (P < 0.01). Multivariate analyses indicated that HDL-C was an independent prognostic factor associated with shorter OS in training cohorts. These findings were confirmed in both independent validation cohorts (P < 0.01). In vitro experiments demonstrated that HDL could increase cell proliferation, invasion, and colony formation, which were largely dependent on the expression of its receptor SR-B1. Finally, HDL could enhance chemoresistance by protecting cancer cells from apoptosis. CONCLUSIONS: Pretreatment HDL-C is a poor prognostic factor for patients with NPC. This effect may be associated with the ability of HDL to enhance proliferation, colony formation, migration, and chemoresistance in NPC cells.

Proposal for the 8th edition of the AJCC/UICC staging system for nasopharyngeal cancer in the era of intensity-modulated radiotherapy.

BACKGROUND: An accurate staging system is crucial for cancer management. Evaluations for continual suitability and improvement are needed as staging and treatment methods evolve. METHODS: This was a retrospective study of 1609 patients with nasopharyngeal carcinoma investigated by magnetic resonance imaging, staged with the 7th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system, and irradiated by intensity-modulated radiotherapy at 2 centers in Hong Kong and mainland China. RESULTS: Among the patients without other T3/T4 involvement, there were no significant differences in overall survival (OS) between medial pterygoid muscle (MP) ± lateral pterygoid muscle (LP), prevertebral muscle, and parapharyngeal space involvement. Patients with extensive soft tissue involvement beyond the aforementioned structures had poor OS similar to that of patients with intracranial extension and/or cranial nerve palsy. Only 2% of the patients had lymph nodes > 6 cm above the supraclavicular fossa (SCF), and their outcomes resembled the outcomes of those with low extension. Replacing SCF with the lower neck (extension below the caudal border of the cricoid cartilage) did not affect the hazard distinction between different N categories. With the proposed T and N categories, there were no significant differences in outcome between T4N0-2 and T1-4N3 disease. CONCLUSIONS: After a review by AJCC/UICC preparatory committees, the changes recommended for the 8th edition include changing MP/LP involvement from T4 to T2, adding prevertebral muscle involvement as T2, replacing SCF with the lower neck and merging this with a maximum nodal diameter > 6 cm as N3, and merging T4 and N3 as stage IVA criteria. These changes will lead not only to a better distinction of hazards between adjacent stages/categories but also to optimal balance in clinical practicability and global applicability.

Analysis on clinical characteristics and influencing factors of patients with locoregionally advanced nasopharyngeal carcinoma.

BACKGROUND: To explore the independent prognostic factors for the recurrence/metastasis of patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). MATERIALS AND METHODS: A total of 604 patients initially diagnosed as LANPC by pathohistology in Fujian Provincial Cancer Hospital were selected to analyze the relationship between the clinical pathological patterns, therapeutic protocols and clinical stages with the recurrence/metastasis of LANPC. RESULTS: The 1-, 3- and 5-year locoregionally recurrent rates of LANPC patients were 2.0%, 9.5% and 12.9% respectively, with average recurrent period being 78 months. Univariate analysis results indicated that clinical stages had certain influence on the recurrent period of LANPC patients. However, COX regression models showed that ages, genders and clinical stages were not the independent prognostic factors influencing the recurrence. The 1-, 3- and 5-year metastatic rates of LANPC patients were 6.6%, 17.5% and 18.8% respectively, with average metastatic period of 73 months. Univariate analysis results demonstrated that ages, N stages, clinical stages, locations of lymph node, retropharyngeal lymph node and extracapsular invasion of lymph node had certain influence on the metastatic period of LANPC patients. Additionally, further COX regression analysis results suggested that T stages, reduction protocols and extracapsular invasion of lymph node were the independent prognostic factors influencing the metastasis of patients with LANPC, in which T stages and extracapsular invasion of lymph node were the pestilent factors while reduction protocols the protective factor. CONCLUSIONS: Induction chemotherapy is beneficial to LANPC patients with initial treatment, and the metastatic rate decreases greatly after the application of reduction chemotherapy.

Multi-subject atlas-based auto-segmentation reduces interobserver variation and improves dosimetric parameter consistency for organs at risk in nasopharyngeal carcinoma: A multi-institution clinical study.

BACKGROUND AND PURPOSE: To assess whether consensus guideline-based atlas-based auto-segmentation (ABAS) reduces interobserver variation and improves dosimetric parameter consistency for organs at risk (OARs) in nasopharyngeal carcinoma (NPC). MATERIALS AND METHODS: Eight radiation oncologists from 8 institutes contoured 20 OARs on planning CT images of 16 patients via manual contouring and manually-edited ABAS contouring. Interobserver variation [volume coefficient of variation (CV), Dice similarity coefficient (DSC), three-dimensional isocenter difference (3D-ICD)] and dosimetric parameters were compared between the two methods of contouring for each OAR. RESULTS: Interobserver variation was significant for all OARs in manual contouring, resulting in significant dosimetric parameter variation (P<0.05). Edited ABAS significantly improved multiple metrics and reduced dosimetric parameter variation for most OARs; brainstem, spinal cord, cochleae, temporomandibular joint (TMJ), larynx and pharyngeal constrictor muscle (PCM) obtained most benefit (range of mean DSC, volume CV and main ICD values was 0.36-0.83, 12.1-84.3%, 2.2-5.0mm for manual contouring and 0.42-0.86, 7.2-70.6%, 1.2-3.5mm for edited ABAS contouring, respectively; range of dose CV reduction: 1.0-3.0%). CONCLUSION: Substantial objective interobserver differences occur during manual contouring, resulting in significant dosimetric parameter variation. Edited ABAS reduced interobserver variation and improved dosimetric parameter consistency, particularly for brainstem, spinal cord, cochleae, TMJ, larynx and PCM.

[Clinical analysis of 60 cases with radiative nasopharyngeal necrosis in nasopharyngeal carcinoma].

OBJECTIVE: To study the clinical characteristics, diagnosis, treatment and prognostic factors of patients with postradiation nasopharyngeal necrosis (PRNN) in nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with PRNN were studied retrospectively, 50 males and 10 females, age ranging from 30 - 70 years of (median 51.5 years). All patients were treated with endoscopic debridement and systemic or local anti-inflammatory treatment. Kruskal-Wallis H test was used to assess the interval time between irradiation completion and necrosis onset and related factors of treatment outcome. Multivariate Cox proportional hazards regression survival analysis was performed to analyze risk factors. RESULTS: The latent period between the last irradiation and the onset of the symptom ranged from 1 to 156 months, with a median of 5 months. The median interval time was 7.0 months in 1 course group and 4.5 months in ≥2 courses group (χ2=5.527, P=0.031), and 7.5 months in T2 group and 5.0 months in ≥T3 group (χ2=4.330, P=0.037), respectively. Forty-one patients of them had nasopharyngeal infection, and the difference in curative effect between infection group and non-infection group was significantly (χ2=14.775, P<0.001). Symptoms were alleviated in all patients after endoscopic debridement and systemic or local anti-inflammatory treatment. Follow-up for all patients ranged from 2 to 46 months (median 12.5 months). Seven patients with internal carotid artery exposure died of sudden nasopharyngeal massive bleeding and fifteen patients died of tumor or systemic exhaustion; five cases were lost, and the rest were all in survival. Inter carotid artery erosion was an independent prognostic risk factor according to multivariate Cox proportional hazards regression survival analysis (P<0.05). CONCLUSIONS: Endoscopic debridement is effective in treating irradiation-related nasopharyngeal necrosis. The occurrence of nasopharyngeal necrosis is related to infection, irradiation dose and course, and T stage. Internal carotid artery erosion is a severe situation and also an independent prognostic factor for the patients. The most common causes of death were nasopharyngeal bleeding and systemic exhaustion.

Prognostic factors of 305 nasopharyngeal carcinoma patients treated with intensity-modulated radiotherapy.

BACKGROUND AND OBJECTIVE: Radiotherapy is effective in treating nasopharyngeal carcinoma (NPC). This study evaluated the treatment efficacy, toxicity, and prognostic factors of intensity-modulated radiotherapy (IMRT) in the treatment NPC. METHODS: Between September 2003 and September 2006, 305 patients with NPC were treated with IMRT in Fujian Provincial Cancer Hospital. IMRT was delivered as follows: gross tumor volume (GTV) received 66.0-69.8 Gy in 30-33 fractions, high-risk clinical target volume (CTV-1) received 60.0-66.65 Gy, low-risk clinical target volume (CTV-2) and clinical target volume of cervical lymph node regions (CTV-N) received 54.0-55.8 Gy. Patients with stages III or IV disease also received cisplatin-based chemotherapy. All patients were assessed for local-regional control, survival, and toxicity. RESULTS: With a median follow-up of 35 months (range, 5-61 months), there were 16, 8, and 39 patients who had developed local, regional, and distant recurrence, respectively. The 3-year rates of local control, regional control, metastasis-free survival, disease-free survival, and overall survival were 94.3%, 97.7%, 86.1%, 80.3%, and 89.1%, respectively. Multivariate analyses revealed that T-classification had no predictive value for local control and survival, whereas N-classification was a significant prognostic factor for overall survival (P < 0.001), metastasis-free survival (P < 0.001), and disease-free survival (P = 0.003). For stages III-IV disease, concurrent and adjuvant chemotherapy did not influence prognosis. The most severe acute toxicities included Grade III mucositis in 14 patients (4.6%), Grade III skin desquamation in 90 (29.5%), and Grades III-IV leucocytopenia in 20 (6.5%). There were 7% patients with Grade II xerostomia after 2 years of IMRT, no Grades 3 or 4 xerostomia was detected. CONCLUSIONS: IMRT provided favorable locoregional control and survival rates for patients with NPC, even in those with locally advanced disease. The acute and late toxicities were acceptable. N-classification was the main factor of prognosis. Further study is needed on chemotherapy for patients with NPC.

[Concurrent control study of different radiotherapy for primary nasopharyngeal carcinoma: intensity-modulated radiotherapy versus conventional radiotherapy].

BACKGROUND AND OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has recently gained popularity in the treatment of nasopharyngeal carcinoma (NPC) and improved the local-regional control rate. This study was to explore whether IMRT could improved the survival rate while reduce the radiation-related injury for primary NPC patients compared with conventional radiotherapy (CRT). METHODS: From Nov. 2003 to Dec. 2005, 190 patients with NPC treated with IMRT in a single hospital were retrospectively analyzed. Another 190 patients treated with conventional radiotherapy at the same period were matched by prognostic factors respectively. The survival status and treatment-induced adverse effects were investigated. Treatment results, the occurrence and severity of adverse effects of two groups were compared. RESULTS: In the treatment of NPC, IMRT was superior to CRT in term of 4-year local regional control rate, relapse-free survival rate without reducing the overall survival rate. But there were no significant differences in the 4-year progress-free survival rate and distant metastasis-free survival rate between the two groups. Significant reductions of the occurrence rates and severity of acute skin reaction, neck fibrosis, trismus and xerostomia were noted in IMRT arm. But there were no differences in mucositis, hematological toxicity, hearing loss and radiation induced cranial neuropathy between IMRT arm and CRT arm. CONCLUSIONS: IMRT could improve the local regional control rate and relapse-free survival rate while reduce some radiation-related complications in patients with NPC. But the improvement of overall survival rate did not reach significant level.

[Long-term efficacy of external radiotherapy plus intracavitary hyperfractionated brachytherapy on nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Intracavitary hyperfractionated brachytherapy is one of the main methods in brachytherapy for early stage nasopharyngeal carcinoma (NPC). We developed the parapharyngeal space interstitial brachytherapy for the NPC patients with residual tumor in the parapharyngeal space after external radiotherapy, and used hyperfractionated brachytherapy as a boosting radiation for the locally advanced patients who have no tumor invasion in the base of skull. This study was to analyze the long-term efficacy of external radiotherapy plus intracavitary hyperfractionated brachytherapy on NPC, and explore the clinical value and suitable dose. METHODS: From Jan. 1998 to Dec. 2002, 352 NPC patients were treated by external radiotherapy plus intracavitary hyperfractionated brachytherapy in Fujian Provincial Tumor Hospital. The parapharyngeal space interstitial brachytherapy was used in the patients with residual tumor in the parapharyngeal space after external radiotherapy. The external irradiation dose varied from 50 to 70 Gy. Brachytherapy was delivered by 2.5-3.0 Gy per fraction, and 2 fractions per day with an interval of 6 h; the total dose ranged from 5 to 32 Gy with a median of 17 Gy. RESULTS: The overall 1-, 2-, 3-, and 5-year disease-free survival rates were 97.0%, 91.3%, 87.6%, and 84.7%, respectively. The 5-year survival rate was significantly higher in stage I-II patients than in stage III-IV patients (88.2% vs. 79.2%, P=0.016)û but the local control rate was similar in the 2 groups (94.1% vs. 91.7%). Thirty-two (9.4%) patients had radiation injury at the lower cranial nerve. CONCLUSION: External radiotherapy plus intracavitary and interstitial hyperfractionated brachytherapy can improve local control rate and survival rate of NPC, but the occurrence rate of radiation injury at the lower cranial nerve is higher in the patients with parapharyngeal space involvement than in other patients.

[Prognostic factors for brain metastatic tumors treated with stereotactic radiosurgery].

OBJECTIVE: To assess the clinical outcome of brain metastatic tumors treated with linac-based stereotactic radiosurgery (SRS) and evaluate the potential prognostic factors. METHODS: We reviewed 102 patients with 131 brain metastatic tumors treated with a linac-based SRS from 1994 to 2002, including 78 patients with solitary and 24 with multiple brain metastases, with the diameter of tumor all within 4 cm. Among these 102 patients, 18 received planned whole-brain radiation therapy (WBRT) before or after SRS. Ninety-three patients with 120 lesions were evaluated for local tumor control analysis with follow-up imaging data. The patients' survival and local control of the tumors were estimated using Kaplan-Meier method, and the potential prognostic factors were analyzed with univariate and multivariate analysis. RESULTS: The overall local tumor control rate and the actuarial local tumor control rate at 1 year were 92.5% and 87.6%, respectively. The tumor volume was the single significant predictor for local tumor control (P=0.035). The median survival of the 102 patients was 11 months. In univariate analysis, patients aged over 60 years (P=0.038) with KPS score above 70 (P=0.001), absence of extracranial metastases (P=0.031) and administration of planned WBRT (P=0.025) were significant factors for survival. After adjustment of multivariate analysis, only KPS score was identified as the independent predictor (P=0.033). CONCLUSION: SRS is an effective method for treatment of brain metastases, and multiple factors may affect the local tumor control and survival of the patients.