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

2019 ◽  
Vol 37 (35) ◽  
pp. 3369-3376 ◽  
Author(s):  
Carlos Rodriguez-Galindo ◽  
Mark D. Krailo ◽  
Matthew J. Krasin ◽  
Li Huang ◽  
M. Beth McCarville ◽  
...  

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.

2020 ◽  
Vol 12 ◽  
pp. 175883592092821
Author(s):  
Li-Ting Liu ◽  
Yu-Jing Liang ◽  
Shan-Shan Guo ◽  
Hao-Yuan Mo ◽  
Ling Guo ◽  
...  

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.


2020 ◽  
Vol 12 ◽  
pp. 175883592093742 ◽  
Author(s):  
Liang Peng ◽  
Jia-Luo Chen ◽  
Guang-Li Zhu ◽  
Cheng-Long Huang ◽  
Jun-Yan Li ◽  
...  

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.


2012 ◽  
Vol 30 (26) ◽  
pp. 3181-3186 ◽  
Author(s):  
David M. Ashley ◽  
Thomas E. Merchant ◽  
Douglas Strother ◽  
Tianni Zhou ◽  
Patricia Duffner ◽  
...  

Purpose P9934 was a prospective trial of systemic chemotherapy, second surgery, and conformal radiation therapy (CRT) limited to the posterior fossa and primary site for children between 8 months and 3 years old with nonmetastatic medulloblastoma. The study was open from June 2000 until June 2006. Patients and Methods After initial surgery, children received four cycles of induction chemotherapy, followed by age- and response-adjusted CRT to the posterior fossa (18 or 23.4 Gy) and tumor bed (cumulative 50.4 or 54 Gy) and maintenance chemotherapy. Neurodevelopmental outcomes were evaluated and event-free survival (EFS) results were directly compared with a previous study of multiagent chemotherapy without irradiation (Pediatric Oncology Group [POG] trial 9233). Results Seventy-four patients met eligibility requirements. The 4-year EFS and overall survival probabilities were 50% ± 6% and 69% ± 5.5%, respectively, which compared favorably to the results from POG 9233. Analysis showed that the desmoplastic/nodular subtype was a favorable factor in predicting survival. Our 4-year EFS rate was 58% ± 8% for patients with desmoplasia. Whereas seven of 10 patients who had disease progression before CRT had primary-site failure, 15 of 19 patients who progressed after CRT had distant-site failure. Neurodevelopmental assessments did not show a decline in cognitive or motor function after protocol-directed chemotherapy and CRT. Conclusion The addition of CRT to postoperative chemotherapy in young children with nonmetastatic medulloblastoma increased event-free survival compared with the use of postoperative chemotherapy alone. Future studies will use histopathologic typing (desmoplastic/nodular versus nondesmoplastic/nodular) to stratify patients for therapy by risk of relapse.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6004-6004 ◽  
Author(s):  
Ming-Yuan Chen ◽  
Qi Yang ◽  
Minghuang Hong ◽  
Ming-Huang Hong

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.


2021 ◽  
Vol 11 ◽  
Author(s):  
Horace Cheuk-Wai Choi ◽  
Sik-Kwan Chan ◽  
Ka-On Lam ◽  
Sum-Yin Chan ◽  
Sze-Chun Chau ◽  
...  

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.


2008 ◽  
Vol 26 (4) ◽  
pp. 633-638 ◽  
Author(s):  
Paul A. Meyers ◽  
Cindy L. Schwartz ◽  
Mark D. Krailo ◽  
John H. Healey ◽  
Mark L. Bernstein ◽  
...  

Purpose To compare three-drug chemotherapy with cisplatin, doxorubicin, and methotrexate with four-drug chemotherapy with cisplatin, doxorubicin, methotrexate, and ifosfamide for the treatment of osteosarcoma. To determine whether the addition of muramyl tripeptide (MTP) to chemotherapy enhances event-free survival (EFS) and overall survival in newly diagnosed patients with osteosarcoma. Patients and Methods Six hundred sixty-two patients with osteosarcoma without clinically detectable metastatic disease and whose disease was considered resectable received one of four prospectively randomized treatments. All patients received identical cumulative doses of cisplatin, doxorubicin, and methotrexate and underwent definitive surgical resection of primary tumor. Patients were randomly assigned to receive or not to receive ifosfamide and/or MTP in a 2 × 2 factorial design. The primary end points for analysis were EFS and overall survival. Results In the current analysis, there was no evidence of interaction, and we were able to examine each intervention separately. The chemotherapy regimens resulted in similar EFS and overall survival. There was a trend toward better EFS with the addition of MTP (P = .08). The addition of MTP to chemotherapy improved 6-year overall survival from 70% to 78% (P = .03). The hazard ratio for overall survival with the addition of MTP was 0.71 (95% CI, 0.52 to 0.96). Conclusion The addition of ifosfamide to cisplatin, doxorubicin, and methotrexate did not enhance EFS or overall survival for patients with osteosarcoma. The addition of MTP to chemotherapy resulted in a statistically significant improvement in overall survival and a trend toward better EFS.


2021 ◽  
Author(s):  
Hao-Yun Tao ◽  
Hui Liu ◽  
Cai-Xian He ◽  
Ran Li ◽  
Kun-Peng Du ◽  
...  

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.


2021 ◽  
Vol 10 ◽  
Author(s):  
Rui Zou ◽  
Jing-Jing Yuan ◽  
Qiang Li ◽  
Jian-Wu Ding ◽  
Bing Liao ◽  
...  

PurposeTo analyze the outcomes and toxicities of induction chemotherapy (ICT) followed by concurrent chemoradiotherapy (CCRT) plus adjuvant chemotherapy (ACT) in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).MethodsRetrospective analysis of 163 patients with LA-NPC referred from August 2015 to December 2018 was carried out. All patients underwent platinum-based ICT followed by CCRT plus ACT.ResultsThe median follow-up time was 40 months, ranging from 5 to 69 months. The 3-year disease-free survival (DFS), overall survival (OS), locoregional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates were 80.8, 90.0, 91.6, and 87.4%, respectively. The most frequent acute grade 3/4 adverse events were leukopenia (66.8%), neutropenia (55.8%), mucositis (41.1%), thrombocytopenia (27.0%), and anemia (14.7%).ConclusionICT followed by CCRT plus ACT did not seemingly enhance DFS and OS in LA-NPC patients compared to the addition of ICT to CCRT (historical controls). In contrast, ICT followed by CCRT plus ACT had more acute adverse events than ICT followed by CCRT. Longer-term clinical studies are required to examine the treatment outcomes and late toxicities.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1414-1414
Author(s):  
Donna L Johnston ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Betsy A. Hirsch ◽  
Nyla A. Heerema ◽  
...  

Abstract Abstract 1414 Introduction: Studies of acute myeloid leukemia (AML) in adults have documented that abnormalities of chromosome 5q (-5/5q-), primarily deletions, confer a poor prognosis. However, there are no large studies that specifically focus on -5/5q- in pediatric AML. Methods: To elucidate the disease correlates of this group, we retrospectively analyzed cytogenetic data from 5 studies of childhood AML: Children's Oncology Group (COG-AAML03P1), Children's Cancer Group (CCG-2961 and 2891) and Pediatric Oncology Group (POG-8821 and 9421). Data from all patients whose cytogenetic clones included -5/5q-, with the exception of those with acute promyelocytic leukemia (M3) or Down syndrome, were included. A total of 2035 patients from these 5 studies had cytogenetic data available for review. Results: Twenty-two (1.1%) of the 2035 patients had −5 or 5q-. The majority of these patients were male (63.6%). The median age was 12.9 years (range 0.3–20.7 years) with a significant number of patients in the 11–21 year age range (63.6%, p=0.032). The median white blood cell count was 17.4 ×103/μL (range 1.4–98 ×103/μL) and the median bone marrow blast percentage was 77% (range 15–99%). Patients with -5/5q- had a significantly higher median platelet count at diagnosis than those without this abnormality (88×103/μL versus 53×103/μL, p=0.015). Of the 22 patients with -5/5q-, their FAB classification showed that a significant number of patients had M0 morphology (28.6%, p<0.001) versus patients without -5/5q- (2.6%). The remaining patients had M1 morphology (23.8%), M2 (19%), M4 (9.5%), M5 (9.5%), M6 (4.8%) and M7 (4.8%) morphology. Eighteen of the 22 patients (81.8%) had a complete response (CR) to induction chemotherapy. The 5-year event free survival (EFS) from the time of diagnosis for these 22 patients was 27% (±19%) and the 5-year overall survival (OS) was 32% (±20%). The 5-year EFS and OS for the patients on these studies without -5/5q- were 41% (±2%) and 51% (±2%) respectively. The 5-year EFS and OS rates were not significantly different between the two groups (p=0.182 and 0.120 respectively). For the 18 patients who achieved a CR with induction chemotherapy, from time of CR the 5-year disease free survival (DFS) was 33% (±22%), the 5-year OS was 39% (±25%), the 5-year relapse risk (RR) was 61% (±23%) and the 5-year treatment related mortality (TRM) was 6% (±11%). For the 1674 patients without -5/5q- who obtained a CR after induction, from the time of CR the 5-year DFS was 47% (±2%), OS was 57% (±2%), RR was 44% (±3%) and TRM was 9% (±5%). None of these values were significantly different between the groups (p>0.1). Conclusions: In this, the largest retrospective study of pediatric patients with AML and -5/5q- to date, this cytogenetic subgroup was found to have a poor outcome. The median 5-year overall survival across studies was 32%, and the median 5-year event free survival was 27%. These findings support the use of more aggressive therapy for the treatment of children with -5/5q- AML, as has been previously supported based on data from adults with -5/5q- AML. This subset of patients may also benefit from treatment with innovative agents. Disclosures: No relevant conflicts of interest to declare.


Sign in / Sign up

Export Citation Format

Share Document