Treatment effects of cumulative cisplatin dose during radiotherapy following induction chemotherapy in nasopharyngeal carcinoma: propensity score analyses

Background: The treatment effects of cumulative cisplatin dose (CCD) during radiotherapy (RT) following induction chemotherapy (IC) have not been determined for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 3460 patients with locoregionally advanced NPC who were treated with IC plus cisplatin-based concurrent chemoradiotherapy or RT alone were included in this retrospective study. Three CCD groups (0 mg/m2 ⩽ CCD <100 mg/m2, 100 mg/m2 ⩽ CCD <200 mg/m2, CCD ⩾200 mg/m2) were balanced through the inverse probability of treatment weighting based on propensity scores estimated by a general boosted model. The primary endpoint was overall survival (OS); the secondary endpoints were distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS). Results: CCD ⩾200 mg/m2 and <200 mg/m2 exhibited similar treatment effects for OS and DMFS, and were both superior to CCD <100 mg/m2 for OS and DMFS in patients with stage IVa NPC. The three CCD groups achieved similar treatment effects for patients with stage II–III NPC. After IC, CCD during RT appeared to exert little treatment effect on LRFS. Conclusion: The CCD during RT exerts treatment effects and improves OS by reducing the risk of distant metastasis for patients with stage IVa NPC following IC, and CCD <200 mg/m2 (mainly 160 mg/m2 in this group) is recommended. However, RT alone may be sufficient after IC in patients with stage II–III NPC.

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Adjuvant Chemotherapy Following Combined Induction Chemotherapy and Concurrent Chemoradiotherapy Improves Survival in N2-3-positive Nasopharyngeal Carcinoma Patients

10.21203/rs.3.rs-848732/v1 ◽

2021 ◽

Author(s):

Hao-Yun Tao ◽

Hui Liu ◽

Cai-Xian He ◽

Ran Li ◽

Kun-Peng Du ◽

...

Keyword(s):

Adjuvant Chemotherapy ◽

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Distant Metastasis ◽

Concurrent Chemoradiotherapy ◽

Cox Regression ◽

Disease Free Survival ◽

Clinical Value ◽

Free Survival ◽

Kaplan Meier

Abstract Objective: This study aimed to explore the clinical value of adjuvant chemotherapy (ACT) in locoregionally advanced nasopharyngeal carcinoma (LANC) following concurrent chemoradiotherapy (CCRT) and induction chemotherapy (ICT).Methods: We included 839 newly diagnosed LANC patients in the study. ICT plus CCRT (ICT+CCRT group) was administered to 443 patients and 396 patients who received ACT after receiving ICT plus CCRT (ICT+CCRT+ACT group). Univariate and multivariate Cox regression analyses were carried out in this study. Furthermore, to balance the study and control groups, propensity score matching (PSM) was applied.Results: 373 pairs of LANC patients were obtained after the PSM analysis. We found that ACT following ICT+CCRT had no significant effect on improving the survival of LANC patients. By further exploring the ICT+CCRT+ACT regimen, we excluded N0-1-positive patients and performed PSM in the ICT+CCRT and ICT+CCRT+ACT groups again. Each group consisted of 237 patients. Kaplan-Meier analysis revealed that there was a difference between the ICT+CCRT and ICT+CCRT+ACT groups in terms of the 5-year overall survival (OS) (78.9% vs. 85.0%, P = 0.034), disease-free survival (DFS) (73.4% vs. 81.7%, P = 0.029), and distant metastasis-free survival (DMFS) (84.9% vs. 76.0%, P = 0.019). In addition, the ICT+CCRT+ACT group had a higher incidence of grade 3-4 acute leukocytopenia/neutropenia.Conclusion: Compared with ICT+CCRT, ACT following ICT plus CCRT can reduce distant metastasis of N2-3-positive LANC and improve the OS and DFS of these patients, thus demonstrating higher clinical feasibility.

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A novel scoring model to predict benefit of additional induction chemotherapy to concurrent chemoradiotherapy in stage II–IVa nasopharyngeal carcinoma

Oral Oncology ◽

10.1016/j.oraloncology.2018.10.007 ◽

2018 ◽

Vol 86 ◽

pp. 258-265 ◽

Cited By ~ 3

Author(s):

Liang Peng ◽

Yu-Pei Chen ◽

Cheng Xu ◽

Ling-Long Tang ◽

Lei Chen ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Stage Ii ◽

Scoring Model

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Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920928214 ◽

2020 ◽

Vol 12 ◽

pp. 175883592092821

Author(s):

Li-Ting Liu ◽

Yu-Jing Liang ◽

Shan-Shan Guo ◽

Hao-Yuan Mo ◽

Ling Guo ◽

...

Keyword(s):

High Risk ◽

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Risk Group ◽

Risk Groups ◽

Rank Test ◽

Intermediate Risk ◽

Free Survival ◽

Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

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Treatment of Childhood Nasopharyngeal Carcinoma With Induction Chemotherapy and Concurrent Chemoradiotherapy: Results of the Children’s Oncology Group ARAR0331 Study

Journal of Clinical Oncology ◽

10.1200/jco.19.01276 ◽

2019 ◽

Vol 37 (35) ◽

pp. 3369-3376 ◽

Cited By ~ 6

Author(s):

Carlos Rodriguez-Galindo ◽

Mark D. Krailo ◽

Matthew J. Krasin ◽

Li Huang ◽

M. Beth McCarville ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Advanced Disease ◽

Black Children ◽

Oncology Group ◽

Event Free Survival ◽

Free Survival ◽

The Impact ◽

To Receive

PURPOSE The treatment of childhood nasopharyngeal carcinoma has been adapted from adult regimens; pediatric-specific studies are limited. The ARAR0331 study sought to evaluate the impact of induction chemotherapy (IC) and concurrent chemoradiotherapy (CCR). PATIENTS AND METHODS Patients with American Joint Committee on Cancer stages IIb to IV were scheduled to receive three cycles of IC with cisplatin and fluorouracil, followed by CCR with three cycles of cisplatin. Patients with complete or partial response to IC received 61.2 Gy to the nasopharynx and neck, and patients with stable disease received 71.2 Gy. RESULTS Between February 2006 and January 2012, 111 patients (75 male) were enrolled. Median age was 15 years, and 46.8% of the patients were African American. After a feasibility analysis, the study was amended to reduce cisplatin to two cycles during CCR. The 5-year event-free survival (EFS) and overall survival estimates were 84.3% and 89.2%, respectively. The 5-year EFS for stages IIb, III, and IV were 100%, 82.8%, and 82.7%, respectively. The 5-year cumulative incidence estimates of local, distant, and combined relapse were 3.7%, 8.7%, and 1.8%, respectively. Patients treated with three versus two CCR cycles of cisplatin had improved 5-year postinduction EFS (90.7% v 81.2%, P = .14). CONCLUSION Patients in ARAR0331 were characterized by advanced disease and by a high proportion of black children and adolescents. Treatment with IC and CRT resulted in excellent outcomes. A radiation dose reduction is possible for patients responding to IC. Although the outcomes are comparable, we observed a trend toward decreased EFS for patients assigned to receive fewer doses of cisplatin during CCR.

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Clinical Profile and Treatment Outcomes in Patients Treated with Intensity-Modulated Radiotherapy (IMRT) for Carcinoma Nasopharynx: A Retrospective Analysis

Journal of Oncology ◽

10.1155/2021/9932749 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Farida Nazeer ◽

R. Rejnish Kumar ◽

Malu Rafi ◽

Tapesh Bhattacharya ◽

Aparna Mullangath Prakasan ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Distant Metastasis ◽

Univariate Analysis ◽

Disease Free Survival ◽

Stage Iv ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Pattern Of Failure ◽

Free Survival

Objective. To retrospectively evaluate the clinical outcome of carcinoma nasopharynx patients treated with the IMRT technique. Methods. Eighty-one nasopharyngeal carcinoma patients who were treated with IMRT with or without chemotherapy between the period January 2011 and December 2014 at a comprehensive tertiary cancer center, Kerala, India, were included in the study. The mean age was 43 years (range 13–77 years), and majority of the patients were males (67.9%). The stagewise distribution of disease at presentation was 2 (2.5%) in stage I, 19 in stage II (23.5%), 31 (38.3%) in stage III, and 29 (35.8%) in stage IV. All patients were treated using simultaneous integrated boost (SIB) schedule using IMRT with 6 MV photon to a dose of 66 Gy in 30 fractions, 2.2 Gy per fraction prescribed to high-risk PTV; 60 Gy in 30 fractions, 2 Gy per fraction to intermediate risk PTV; and 54 Gy in 30 fractions, 1.8 Gy per fraction to low-risk PTV. Concurrent chemotherapy with cisplatin was offered to patients with stage II and above disease. Neoadjuvant chemotherapy with cisplatin and 5FU was given to patients with initially advanced disease (T3, T4, N2, and N3). Survival estimates were generated using the Kaplan–Meier method. The univariate analysis was performed using log-rank tests. Results. The 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.5%, 87%, 61.6%, and 62.5%, respectively. The 5-year OS was 100% for stage I (n = 2), 67% for stage II (n = 19), 70.4% for stage III (n = 31), and 68.1% for stage IV (n = 29). The DFS at 5 years was 100% for stage I, 61.1% for stage II, 56.2% for stage III, and 84.8% for stage IV disease. The univariate analysis showed that age, nodal stage, and use of induction chemotherapy showed an improved trend towards OS, though the results were not statistically significant. The predominant pattern of failure in the present study was distant metastasis. Most patients who developed distant metastasis in our study had either an advanced T stage or N3 disease at presentation. Conclusion. The present study shows our initial experience with IMRT for nasopharyngeal carcinoma. The compliance to RT was good in this study. The 5-year LRC and OS rate of nasopharyngeal carcinoma patients treated with IMRT were 87.5% and 62.5%. Distant metastasis was the main pattern of failure.

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Induction chemotherapy followed by concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: Long-term results of a phase 3 multicenter randomized controlled trial.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6004 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6004-6004 ◽

Cited By ~ 2

Author(s):

Ming-Yuan Chen ◽

Qi Yang ◽

Minghuang Hong ◽

Ming-Huang Hong

Keyword(s):

Clinical Trial ◽

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Long Term Results ◽

Phase 3 ◽

Free Survival ◽

Multicenter Randomized Controlled Trial

6004 Background: Initial 3-year results from our clinical trial in locoregionally advanced nasopharyngeal carcinoma (NPC) patients showed that induction chemotherapy (IC) with cisplatin and fluorouracil (PF) resulted in improved disease-free survival (DFS) with a marginally significant effect on distant metastasis-free survival (DMFS), but the effect of IC on locoregional relapse-free survival (LRRFS) and overall survival (OS) did not differ significantly. Here, we present 5-year follow-up results. Methods: Our trial was a randomized, open-label phase 3 trial comparing IC followed by concurrent chemoradiotherapy (CCRT) versus CCRT alone in patients with stage III-IVB (except T3N0-1) NPC. The IC followed by CCRT group received cisplatin (80 mg/m² d1) and fluorouracil (800 mg/m² d1-5) every three weeks for two cycles before CCRT. Both groups were treated with 80 mg/m² cisplatin every three weeks concurrently with radiotherapy. The primary endpoints were DFS and DMFS. We did efficacy analyses in the 476 randomized patients (intention-to-treat population). Results: After a median follow-up of 82.6 months, the 5-year DFS rate was 73.4% (95% confidence interval (CI) 67.7-79.1) in the IC followed by CCRT group and 63.1% (95% CI 56.8-69.4) in the CCRT alone group (P = 0.005). The 5-year DMFS rate was also significantly higher in the IC followed by CCRT group (82.8%, 95% CI 77.9-87.7) than in the CCRT alone group (73.1%, 95% CI 67.2-79.0, P = 0.013). Our updated analysis revealed an OS benefit of IC: the 5-year OS rate was 80.8% in the IC followed by CCRT group versus 76.8% in the CCRT alone group (P = 0.045). There were no significant differences in the rate of grade 3–4 late adverse events during follow-up between the two groups. Conclusions: IC followed by CCRT provides long-term DFS, DMFS, and OS benefits compared with CCRT alone in locoregionally advanced NPC and, therefore, can be recommended for these patients. Clinical trial information: NCT00705627.

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The Most Efficacious Induction Chemotherapy Regimen for Locoregionally Advanced Nasopharyngeal Carcinoma: A Network Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.626145 ◽

2021 ◽

Vol 11 ◽

Author(s):

Horace Cheuk-Wai Choi ◽

Sik-Kwan Chan ◽

Ka-On Lam ◽

Sum-Yin Chan ◽

Sze-Chun Chau ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Fixed Effects ◽

Concurrent Chemoradiotherapy ◽

Meta Analysis ◽

Intensity Modulated Radiation Therapy ◽

Progression Free Survival ◽

Free Survival ◽

Hazard Ratios ◽

Analysis Models

BackgroundInduction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT) for non-metastatic locoregionally advanced nasopharyngeal carcinoma (NPC) has gained considerable attention. However, the most efficacious IC regimens remain investigational. We aimed to compare the survival benefits of all available IC regimens followed by CCRT in this network meta-analysis.MethodsAll randomized-controlled trials of CCRT with or without IC in non-metastatic locoregionally advanced NPC were included, with an overall nine trials of 2,705 patients counted in the analysis. CCRT alone was the reference category. Eight IC regimens followed by CCRT were analyzed: docetaxel + cisplatin (DC), gemcitabine + carboplatin + paclitaxel (GCP), gemcitabine + cisplatin (GP), mitomycin + epirubicin + cisplatin + fluorouracil + leucovorin (MEPFL), cisplatin + epirubicin + paclitaxel (PET), cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX) and cisplatin + fluorouracil (PF), cisplatin + capecitabine (PX). Fixed-effects frequentist network meta-analysis models was applied and P-score was used to rank the treatments.ResultsDC, GP, and PX were the top three IC regimens with the highest probability of benefit on overall survival (OS). Their corresponding hazard ratios (HRs) (95% CIs) compared with CCRT alone were of 0.24 (0.08–0.73), 0.43 (0.24–0.77), and 0.54 (0.27–1.09) and the respective P-scores were 94%, 82%, and 68%. The first three IC regimens showing significantly improved progression-free survival (PFS) were PX, followed by GP and DC with respective HRs of 0.46 (0.24–0.88), 0.51 (0.34–0.77), and 0.49 (0.20–1.20), and P-scores of 82%, 78%, and 74%. Among the studies in the intensity-modulated radiation therapy (IMRT) era, GP and PX were the best performed IC regimens, whilst DC performed the best among non-IMRT studies. Doublet and gemcitabine-based IC regimens had better survival benefits compared to triplet and taxane-based IC regimens, respectively.ConclusionsGiven its consistent superiority in both OS and PFS, DC, GP, and PX ranked among the three most efficacious IC regimens in both the overall and subgroup analysis of IMRT or non-IMRT studies. Exploratory analyses suggested that doublet and gemcitabine-based IC regimens showed better survival performance.

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Impact of RhoA overexpression on clinical outcomes in cervical squamous cell carcinoma treated with concurrent chemoradiotherapy

Journal of Radiation Research ◽

10.1093/jrr/rrz093 ◽

2020 ◽

Vol 61 (2) ◽

pp. 221-230

Author(s):

Keiichi Tanaka ◽

Yoshitaka Matsumoto ◽

Hitoshi Ishikawa ◽

Nobuyoshi Fukumitsu ◽

Haruko Numajiri ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Cancer Patients ◽

Clinical Outcomes ◽

Squamous Cell ◽

Distant Metastasis ◽

Concurrent Chemoradiotherapy ◽

Cervical Squamous Cell Carcinoma ◽

Stage Ii ◽

Free Survival

Abstract The Rho-associated coiled-coil-containing protein kinase (ROCK) pathway is known to influence metastasis in several cancers; however, the impact of the pathway on clinical outcomes in patients undergoing radiotherapy remains unknown. In the present study, the expression of RhoA, RhoC, ROCK-1, ROCK-2 and p53 was immunohistochemically evaluated using biopsy specimens obtained from 49 patients with stage II–III cervical squamous cell carcinoma treated with concurrent chemoradiotherapy (CCRT). The relationship between the expression of these proteins and patient outcomes was investigated. RhoA overexpression was associated with significantly impaired disease-free survival and distant metastasis-free survival (P = 0.045 and P = 0.041, respectively) in stage III cancer patients. No differences in survival were observed based on the expression of the other proteins among stage III cancer patients. In stage II cancer patients, no differences in survival were noted based on the expression of any of the proteins. The expression of RhoA was able to successfully differentiate cervical cancer patients with distant metastasis after CCRT. This information may help stratify patients according to the risk of metastasis, thereby leading to the potential to provide individualized treatment.

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