Concurrent-Adjuvant Chemoradiation Therapy for Stage III-IVB Nasopharyngeal Carcinoma—Exploration for Achieving Optimal 10-Year Therapeutic Ratio

Ng, Wai Tong; Tung, Stewart Y.; Lee, Victor; Ngan, Roger K.C.; Choi, H.C.W.; Chan, Lucy; Leung, TW; Siu, Lillian L.; Lu, Tai Xiang; Tan, Terence; Tan, Eng Huat; Sze, Henry C.K.; Ng, Aik Seng; Yiu, Harry; O’Sullivan, Brian; Chappell, Rick; Lee, Anne W.M.

doi:10.1016/j.ijrobp.2018.04.069

Cited by 26 publications

(18 citation statements)

References 13 publications

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“…[4][5][6][7] However, the NPC-9901 trial cautioned that the benefit for distant control was inadequate, particularly for patients with regionally advanced disease, partly due to poor compliance in the adjuvant phase. 8,9 Cancer August 15, 2020…”

Section: Introductionmentioning

confidence: 99%

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NPC‐0501 trial on the value of changing chemoradiotherapy sequence, replacing 5‐fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma

Lee

Ngan

et al. 2020

Cancer

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BACKGROUND: A current recommendation for the treatment of patients with locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy (RT) with concurrent cisplatin followed by adjuvant cisplatin and 5-fluorouracil (PF). This randomized NPC-0501 trial evaluated the therapeutic effect of changing to an induction-concurrent sequence or acceleratedfractionation sequence, and/or replacing 5-fluorouracil with capecitabine (X). METHODS: Patients with American Joint Committee on Cancer/International Union Against Cancer stage III to stage IVB NPC initially were randomly allocated to 1 of 6 treatment arms (6-arm full-randomization cohort). The protocol was amended in 2009 to permit centers to opt out of randomization regarding fractionation (3-arm chemotherapy cohort). RESULTS: A total of 803 patients were accrued (1 of whom was nonevaluable) from 2006 to 2012. Based on the overall comparisons, neither changing the chemotherapy sequence nor accelerated fractionation improved treatment outcome. However, secondary analyses demonstrated that when adjusted for RT parameters and other significant factors, the inductionconcurrent sequence, especially the induction-PX regimen, achieved significant improvements in progression-free survival (PFS) and overall survival. Efficacy varied among different RT groups: although no impact was observed in the accelerated-fractionation group and the 3-arm chemotherapy cohort, a comparison of the induction-concurrent versus concurrent-adjuvant sequence in the conventionalfractionation group demonstrated a significant benefit in PFS (78% vs 62% at 5 years; P = .015) and a marginal benefit in overall survival (84% vs 72%; P = .042) after adjusting for multiple comparisons. Comparison of the induction-PX versus the adjuvant-PF regimen demonstrated better PFS (78% vs 62%; P = .027) without an increase in overall late toxicity. CONCLUSIONS: For patients irradiated using conventional fractionation, changing the chemotherapy sequence from a concurrent-adjuvant to an induction-concurrent sequence, particularly using induction cisplatin and capecitabine, potentially could improve efficacy without an adverse impact on late toxicity. However, further validation is needed for confirmation of these findings.

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Section: Introductionmentioning

confidence: 99%

“…Three subsequent trials confirmed the overall efficacy of this concurrent‐adjuvant strategy 4‐7 . However, the NPC‐9901 trial cautioned that the benefit for distant control was inadequate, particularly for patients with regionally advanced disease, partly due to poor compliance in the adjuvant phase 8,9 …”

Section: Introductionmentioning

confidence: 99%

NPC‐0501 trial on the value of changing chemoradiotherapy sequence, replacing 5‐fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma

Lee

Ngan

et al. 2020

Cancer

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“…A long-term results of a phase 3 multicentre randomised controlled trial reported that adjuvant cisplatin and fluorouracil chemotherapy still failed to demonstrate significant survival benefit after CCRT in locoregionally advanced NPC based on the long-term follow-up data, and addition of adjuvant cisplatin and fluorouracil did not significantly increase late toxicities 14 . Another two 10-year studies have confirmed that the addition of concurrent cisplatin plus adjuvant cisplatin-fluorouracil could significantly improve OS without excessive late toxicities for patients with regionally advanced NPC 19,21 . Li et al undertook a network meta-analysis to establish the optimal chemotherapy strategy in advanced NPC, they found that CCRT + AC achieved better overall survival www.nature.com/scientificreports www.nature.com/scientificreports/ than CCRT (HR, 0.82; 95% CI, 0.67-1.00).…”

Section: Discussionmentioning

confidence: 94%

Prognostic Nomogram For Locoregionally Advanced Nasopharyngeal Carcinoma

Jiang

Pan

et al. 2020

Sci Rep

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the tnM staging system of npc is the most important model for survival prediction. However, this model does not consider the biological variability of the tumor itself. this study aimed to develop a nomogram for predicting the overall survival of loco-regionally advanced nasopharyngeal carcinoma. 487 Patients with confimed nasopharyngeal carcinoma who underwent IMRT and chemotherapy were included in this study. We established prognostic nomogram for overall survival (oS) based on the cox proportional hazards model. the predictive accuracy and discriminative ability were measured using the concordance index (c-index) and calibration curve. nomogram was validated externally by assessing discrimination and calibration using an independent data set. Continuous net reclassification improvement (nRi) and integrated discrimination improvement (iDi) were used to analyze whether nomogram improve the prediction of survival than tnM stage system. Recursive partitioning analysis (RpA) was performed to stratifying risk of patients. Age, t-stage, n-stage, nLR, LDH were included in the nomogram for OS. The C-index of the nomogram for OS were 0.726 (95% CI, 0.690 to 0.762); The calibration curve showed the nomogram was able to predict 5-year OS accurately. The nomogram had a higher C-index than the TNM stage system (0.726 VS 0.632, P-value < 0.001). The NRI was 0.235 (95% CI: 0.129 to 0.396, P < 0.001), the IDI was 0.079 (95% CI: 0.034 to 0.396, p < 0.001). RPA was performed to stratify patients into three risk group, OS was significantly different between all three risk groups. High risk groups can be benefited survival from adjuvant chemotherapy. The nomogram outperformed the tnM staging system in predicting the oS of loco-regionally advanced nasopharyngeal carcinoma underwent intensity modulated radiation therapy and chemotherapy. Nasopharyngeal carcinoma (NPC) is endemic to the south of China and Asia; an NPC incidence of 2 per million people in China has been reported 1. More than 70% of the newly diagnosed cases are classified as locoregionally advanced disease 2. Concurrent chemoradiotherapy is the standard treatment for locally advanced nasopharyngeal carcinoma 3. However, in some patients, the disease progresses within a few years after chemoradiotherapy. Therefore, identifying a prognostic model for early progression would allow for a better therapeutic plan. The TNM staging system of NPC is the most important model for survival prediction. However, this model does not consider the biological variability of the tumor itself. The prognosis of patients at the same stage receiving the same treatment varies greatly. Therefore, another prognostic model, based on the TNM staging system combined with other prognosis factors, has been evaluated 4 ; however, this model was not validated and has limited clinical applicability. Therefore, in this study, we established and validated a nomogram for locoregionally advanced NPC patients who received intensity-modulated radiation therapy (IMRT) and chemotherapy. Results Baseline chara...

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“…Exploratory analyses showed that only patients who could tolerate ≥2 chemotherapy cycles in both the concurrent and adjuvant phases achieved statistically significant improvement in distant control (73% vs. 65%, p = 0.037) and maximum survival gain. 9 The ability to deliver adjuvant chemotherapy is poor in NPC patients because they are still recuperating from the acute CRT toxicities. Therefore, distant failure (~20-30%) remains the leading cause of death in NPC.…”

Section: Chemoradiation Regimensmentioning

confidence: 99%

Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy

Colevas

O’Sullivan

et al. 2019

JNCI: Journal of the National Cancer Institute

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Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer with a distinctive regional and racial prevalence. It is associated with Epstein-Barr virus infection and has a high propensity for regional and distant metastases, while it is very sensitive to radiation and chemotherapy. A common feature of Epstein-Barr virus-positive NPC is the dense infiltration of lymphocytes in the tumor stroma and positive programmed death-ligand 1 expression in tumor cells, making it an attractive target for immunotherapy, especially immune checkpoint inhibitors. As new immunotherapeutic agents are being rapidly adopted in many cancers, including head and neck cancer, the National Cancer Institute sponsored a clinical trial planning meeting to identify opportunities for developing phase II and III trials testing immunotherapy in different stages of NPC. The meeting started with the summary of the biology of the disease, current standards of care, and evidence of immunotherapy in this cancer. Three subcommittees were tasked to develop clinical trials: loco regionally advanced, nonmetastatic NPC; widely metastatic NPC; and either local recurrence after initial treatment or presenting with oligometastatic disease. This article summarizes the proceedings of this clinical trial planning meeting and provides a road map for future trials incorporating immune checkpoint inhibitors for therapeutic management of NPC. This road map, though specific for NPC, may also be applicable to other virally driven cancers that have similar ability to evade the host’s immune system.

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Concurrent-Adjuvant Chemoradiation Therapy for Stage III-IVB Nasopharyngeal Carcinoma—Exploration for Achieving Optimal 10-Year Therapeutic Ratio

Cited by 26 publications

References 13 publications

NPC‐0501 trial on the value of changing chemoradiotherapy sequence, replacing 5‐fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma

NPC‐0501 trial on the value of changing chemoradiotherapy sequence, replacing 5‐fluorouracil with capecitabine, and altering fractionation for patients with advanced nasopharyngeal carcinoma

Prognostic Nomogram For Locoregionally Advanced Nasopharyngeal Carcinoma

Current Treatment Landscape of Nasopharyngeal Carcinoma and Potential Trials Evaluating the Value of Immunotherapy

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