Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

Lee, Anne W.M.; Tung, Stewart Y.; Chan, Anthony T.C.; Chappell, Rick; Fu, Yiu Tung; Lu, Tai Xiang; Tan, Terence; Chua, Daniel T.T.; O’Sullivan, Brian; Xu, Shuning; Pang, Elizabeth; Sze, W.M.; Leung, TW; Kwan, W. H.; Chan, Pak Tat; Liu, Xiu Fang; Tan, Eng Huat; Sham, Jonathan S. T.; Siu, Lillian L.; Lau, W.S.

doi:10.1016/j.ijrobp.2006.03.054

Cited by 149 publications

(117 citation statements)

References 16 publications

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“…Gao once reported an excellent 5-year L-FFS rate of 88.6% in their N 0 NPC series, better than that obtained in our analysis . One of the possible explanations for this difference was that a considerable proportion of patients (Lee et al, 2006), finding that significant improvement only in failure-free survival was achieved in the concurrent chemoradiotherapy arm, when compared with the radiotherapy arm. The results of other studies also demonstrated that chemotherapy was not the significant prognostic factor for patients with N 0 NPC Xie et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

Long Term Outcomes and Prognostic Factors of N₀Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Sun

Chen²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Treatment responses of N 0 stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with N 0 NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with N 0 NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with N 0 NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.

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Section: Discussionmentioning

confidence: 99%

Long Term Outcomes and Prognostic Factors of N₀Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Sun

Chen²,

Chen³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…However, the majority of NPC patients present with a late stage disease accompanying neck nodal metastases when diagnosed, and the cure rate for those advanced NPCs remains unsatisfactory (4). In addition, numerous NPC survivors are often affected by moderate to severe late complications, resulting from the impact of radiation on the organs that are adjacent to the nasopharynx and neck nodes, and chemotherapy in advanced cases further exacerbates these side-effects (5). Therefore, exploring novel therapeutic regimens and improvements in disease monitoring is required.…”

Section: Introductionmentioning

confidence: 99%

Parametric contrast-enhanced ultrasound as an early predictor of radiation-based therapeutic response for lymph node metastases of nasopharyngeal carcinoma

Huang

Zhou

et al. 2014

Molecular and Clinical Oncology

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Abstract. Nasopharyngeal carcinoma (NPC) is a common type of cancer in South East Asia with peculiar epidemiology, pathology, clinical behavior and response to treatment characteristics. To the best of our knowledge, this is the first study to investigate the use of a contrast-enhanced ultrasound (CEUS) as a predictor for the therapeutic response in lymph node metastases of NPC patients treated with radiation-based therapy. Sixty-seven NPC patients with lymph node metastases underwent the lymph nodes CEUS examination twice; pre-and in-treatment (at the 5th fraction radiotherapy), respectively. The CEUS parameters were acquired through Qontrast_4.0 software and mainly included peak intensity (PI) and time to peak (TTP). The response assessment at the lymph nodes revealed a complete response (CR) in 48 patients and partial response (PR) in 19 patients. There was a significant difference in pre-treatment PI (PI pre ) between the patients who showed CR or PR, but the predicted sensitivity and specificity of PI pre was low. The mean in-treatment PI (PI in ) value of the lymph nodes that achieved a CR was 34.24±3.78%, which was significantly higher than the PI in value for PR, 25.62±2.30% (P<0.001). Furthermore, the PI ratio , a PI-quotient, was calculated by dividing the PI in by the corresponding PI pre . The higher PI ratio was also observed in CR lymph nodes (0.81±0.01 vs. 0.66±0.01; P=0.001), and the mean change in PI (PI Δ ; PI Δ = PI pre -PI in ) was smaller in the patients with CR nodes compared to the patients with PR nodes (7.79±3.28 vs. 13.77±1.90%; P=0.000). No difference was observed in TTP pre or TTP in between the CR or PR lymph nodes patients. A receiver operating characteristic curve was constructed to assess the accuracy of the parameters for the prediction of the therapeutic responses. The sensitivity and specificity of PI in in predicting the therapeutic response was 94.3 and 88.2%, and the corresponding figures of the PI ratio were 92.5 and 83.8%, respectively. The CEUS parameters during the early course of radiation-based therapy, PI in and PI ratio , are associated with the therapeutic response of NPC lymph node metastases, with a high predicted sensitivity and specificity, thus yielding the conceivable predictors with the potential to individualize treatment.

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“…Measurements were obtained at baseline (pre-RT), 15 min, 30 min, 1 h, 4 h, and 24 h. Mean ± SE from three independent experiments, each done in triplicate. chemotherapy such as cisplatin, which unfortunately is associated with significant long-term normal tissue toxicities, particularly hearing loss (30,31); hence, any novel therapeutic modalities that could enhance the long-term cure rate of radiation therapy for nasopharyngeal carcinoma would be welcomed.…”

Section: Discussionmentioning

confidence: 99%

Therapeutic Efficacy of Seliciclib in Combination with Ionizing Radiation for Human Nasopharyngeal Carcinoma

Hui

Yue

Shi

et al. 2009

Clinical Cancer Research

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Purpose: Seliciclib is a small-molecule cyclin-dependent kinase inhibitor, which has been reported to induce apoptosis and cell cycle arrest in EBV-negative nasopharyngeal carcinoma cell lines. Because most nasopharyngeal carcinoma patients harbor EBV, we proceeded to evaluate the cytotoxic effects of seliciclib in EBV-positive nasopharyngeal carcinoma models. Experimental Design: Cytotoxicity of seliciclib was investigated in the EBV-positive cell line C666-1 and the C666-1 and C15 xenograft models. Caspase activities and cell cycle analyses were measured by flow cytometry. Efficacy of combined treatment of seliciclib with radiation therapy was also evaluated. Results: Seliciclib caused significant cytotoxicity in the C666-1 cells in a time-and dosedependent manner, with accumulation of cells in both sub-G 1 and G 2 -M phases, indicative of apoptosis and cell cycle arrest, respectively. Caspase-2, -3, -8, and -9 activities were all increased, with caspase-3 being the most significantly activated at 48 h after treatment. These cells also showed a reduction of Mcl-1 mRNA and protein levels. Combined treatment of seliciclib with radiation therapy showed a synergistic interaction with enhanced cytotoxicity in C666-1 cells and delayed repair of double-strand DNA breaks. For in vivo models, significant delays in tumor growth were observed for both C666-1 and C15 tumors, which were associated with enhanced apoptosis as determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and immunohistochemistry analyses. Conclusions: Seliciclib enhanced the antitumor efficacy of radiation therapy in EBVpositive nasopharyngeal carcinoma, characterized by G 2 -M arrest, and apoptosis, associated with an induction in caspase activity. This process is mediated by reduction in Mcl-1 expression and by attenuation of double-strand DNA break repair.

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Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

Cited by 149 publications

References 16 publications

Long Term Outcomes and Prognostic Factors of N₀Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Long Term Outcomes and Prognostic Factors of N₀Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Parametric contrast-enhanced ultrasound as an early predictor of radiation-based therapeutic response for lymph node metastases of nasopharyngeal carcinoma

Therapeutic Efficacy of Seliciclib in Combination with Ionizing Radiation for Human Nasopharyngeal Carcinoma

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Preliminary results of a randomized study (NPC-9902 Trial) on therapeutic gain by concurrent chemotherapy and/or accelerated fractionation for locally advanced nasopharyngeal carcinoma

Cited by 149 publications

References 16 publications

Long Term Outcomes and Prognostic Factors of N0Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Long Term Outcomes and Prognostic Factors of N0Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Parametric contrast-enhanced ultrasound as an early predictor of radiation-based therapeutic response for lymph node metastases of nasopharyngeal carcinoma

Therapeutic Efficacy of Seliciclib in Combination with Ionizing Radiation for Human Nasopharyngeal Carcinoma

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Long Term Outcomes and Prognostic Factors of N₀Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients

Long Term Outcomes and Prognostic Factors of N₀Stage Nasopharyngeal Carcinoma: a Single Institutional Experience with 610 Patients