Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial

Yang, Hongxia; Chen, Xin; Lin, Sheng; Rong, Jin‐Feng; Yang, Mi; Wen, Qinglian; Shang, Chang‐Ling; He, Lvqin; Ren, Pei-Rong; Xu, Shan; Zhang, Jianwen; Liu, Qiaoli; Pang, Haowen; Shi, Xiangxiang; Fan, Juan; Sun, Xiaoyang; Ma, Dong; Tan, Bangxian; Zhang, Tao; Zhang, Ling; Hu, Defeng; Du, Xiaobo; Zhang, Yu; Wen, Shifeng; Zhang, Xiaopeng; Wu, Jingbo

doi:10.1016/j.radonc.2017.07.020

Cited by 82 publications

(67 citation statements)

References 16 publications

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“…In our study, the incidences of severe late radiation‐related toxicities were comparable with those in previous studies of patients with locoregionally advanced NPC treated with conformal radiotherapy . Although IC has the benefit of shrinking tumor volume before radiotherapy, the incidence of late radiation‐related toxicities were similar between both groups, probably because of the inconsistency in target volume delineation based on pre‐IC or post‐IC images . For chemotherapy‐related toxicities, the incidence and severity of long‐term paresthesias are determined mainly by cumulative cisplatin dose and dose intensity .…”

Section: Discussionsupporting

confidence: 84%

“…24,30 Although IC has the benefit of shrinking tumor volume before radiotherapy, the incidence of late radiation-related toxicities were similar between both groups, probably because of the inconsistency in target volume delineation based on pre-IC or post-IC images. 31 For There were no grade 3-4 acute adverse events for nephrotoxicity, ototoxicity, and neurotoxicity. 1 p Values were calculated using the Chi-square test (or Fisher's exact test).…”

Section: Discussionmentioning

confidence: 96%

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

Chen

Zhang

et al. 2019

Intl Journal of Cancer

200

179

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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.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 96%

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

Chen

Zhang

et al. 2019

Intl Journal of Cancer

200

179

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“…The use of induction therapy in T4 and N3 is likely to reduce the target volumes for the definitive chemoradiation therapy. Studies have shown that use of induction therapy successfully reduces the target volumes of RT in order to avoid overdosing of critical neurological structures and reduce RT related toxicities 16, 17. For that reason, it is not surprising that we see higher use of induction therapy in these patients with very advanced disease.…”

Section: Discussionmentioning

confidence: 99%

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care

et al. 2018

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The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T‐ and N‐stage had a higher likelihood of being treated with induction chemotherapy. The 5‐year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3‐T4N1 or TanyN2‐3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3‐T4N1 or TanyN2‐3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone.

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“…First, deintensification of radiation after induction chemotherapy (IC) is potentially feasible to reduce toxicities. According to Yang et al (35) and Zhao et al (36), delineation of GTV on post-IC MRI while lowering prescription dose to shrink GTV significantly decreased radiation dose to organs at risk without damaging long-term survival. Niu et al reported encouraging treatment outcome with reduced dose to optic nerves and chiasm by mid-course replanning during radiation following IC (37).…”

Section: Discussionmentioning

confidence: 99%

Impact of Paranasal Sinus Invasion on Oncologic and Dosimetric Outcomes in Nasopharyngeal Carcinoma Following Intensity-Modulated Radiation Therapy—Implications for Risk Stratification and Planning Optimization

Zhou

Xue

et al. 2020

Front. Oncol.

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Purpose: This study aims to investigate the prognostic value and dosimetric impact of paranasal sinus invasion (PSI) in patients with nasopharyngeal carcinoma (NPC), and further to explore the feasibility of an integrative prognostic model based on anatomic, volumetric, and dosimetric features.Methods: Two hundred six patients with T3 NPC receiving intensity-modulated radiation therapy (IMRT) were retrospectively analyzed. Dosimetric parameters were calculated from dose-volume histograms. Primary gross tumor volume (GTV-P) and dosimetric parameters were categorized using optimal cutpoints determined by R. Local recurrence-free survival (LRFS) was estimated using Kaplan-Meier method. Independent risk factors for LRFS were identified through univariable and multivariable analyses by Cox proportional hazards models.Results: The incidence of PSI was 10.7% (22/206). Patients with PSI had significantly inferior 5-year LRFS (77.3 vs. 93.8%, P = 0.006). IMRT plans for patients with PSI had larger dose heterogeneity, higher frequency of underdosing, and higher maximum dose to optic structures. When categorized by optimal cutpoints, GTV-P > 38.67 cm 3 (5-year LRFS, 84.8 vs. 97.4%, P = 0.008), and V66.88 < 89.87% (5-year LRFS, 67.1 vs. 94.5%, P < 0.001) were associated with significantly worse local outcome. Multivariable analyses showed that PSI, GTV-P > 38.67 cm 3 , and V66.88 < 89.87% were independent risk factors for local relapse, either in patients with or without concurrent chemotherapy. An integrative prognostic model was then established upon the cumulative score of risk factors. Subgroups with score of 0, 1-2, and 3 had distinctive local outcomes; the 5-year LRFS was 96.6, 84.7, and 58.3%, respectively (P < 0.001).Zhou et al. Impact of PSI on NPC Following IMRTConclusions: Paranasal sinus invasion jeopardized local control in T3 NPC patients due to large tumor burden and inadequate radiation dose in GTV-P. The presence of PSI, GTV-P, and radiation underdosing combined are critical for the risk stratification of local failure.

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Treatment outcomes after reduction of the target volume of intensity-modulated radiotherapy following induction chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma: A prospective, multi-center, randomized clinical trial

Cited by 82 publications

References 16 publications

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

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

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care

Impact of Paranasal Sinus Invasion on Oncologic and Dosimetric Outcomes in Nasopharyngeal Carcinoma Following Intensity-Modulated Radiation Therapy—Implications for Risk Stratification and Planning Optimization

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