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Title: Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: Long-term results of Phase III clinical trial

Abstract

Purpose: To update 5-year results of a previously published study on special 7-days-a-week fractionation continuous accelerated irradiation (CAIR) for head-and-neck cancer patients. Methods and Materials: One hundred patients with squamous cell carcinoma of head and neck in Stage T{sub 2-4}N{sub 0-1}M were randomized between two definitive radiation treatments: accelerated fractionation 7 days a week including weekends (CAIR) and conventional 5 days a week (control). Hence the overall treatment time was 2 weeks shorter in CAIR. Results: Five-year local tumor control was 75% in the CAIR group and 33% in the control arm (p < 0.00004). Tumor-cure benefit corresponded with significant improvement in disease-free survival and overall survival rates. Confluent mucositis was the main acute toxicity, with the incidence significantly higher in CAIR patients than in control (respectively, 94% vs. 53%). When 2.0-Gy fractions were used, radiation necrosis developed in 5 patients (22%) in the CAIR group as a consequential late effect (CLE), but when fraction size was reduced to 1.8 Gy no more CLE occurred. Actuarial 5-year morbidity-free survival rate was similar for both treatments. Conclusions: Selected head-and-neck cancer patients could be treated very effectively with 7-days-a-week radiation schedule with no compromise of total dose and with slight 10% reductionmore » of fraction dose (2 Gy-1.8 Gy), which article gives 1 week reduction of overall treatment time compared with standard 70 Gy in 35 fractions over 47-49 days. Although this report is based on the relatively small group of patients, its results have encouraged us to use CAIR fractionation in a standard radiation treatment for moderately advanced head-and-neck cancer patients.« less

Authors:
 [1];  [2];  [3];  [2];  [4];  [5];  [2];  [3];  [3]
  1. Department of Radiation Oncology, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice (Poland). E-mail: skladowski@io.gliwice.pl
  2. Department of Radiotherapy, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice (Poland)
  3. Department of Radiation Oncology, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice (Poland)
  4. (Poland)
  5. Department of Medical Physics, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice (Poland)
Publication Date:
OSTI Identifier:
20850154
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 66; Journal Issue: 3; Conference: 48. annual meeting of the American Society for Therapeutic Radiology and Oncology, Pennsylvania, PA (United States), 5-9 Nov 2006; Other Information: DOI: 10.1016/j.ijrobp.2006.05.026; PII: S0360-3016(06)00865-0; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CARCINOMAS; CLINICAL TRIALS; FRACTIONATED IRRADIATION; HEAD; NECK; NECROSIS; PATIENTS; RADIATION DOSES; RADIOTHERAPY; TOXICITY

Citation Formats

Skladowski, Krzysztof, Maciejewski, Boguslaw, Golen, Maria, Tarnawski, Rafal, Department of Radiobiology and Biostatistics, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice, Slosarek, Krzysztof, Suwinski, Rafal, Sygula, Mariusz, and Wygoda, Andrzej. Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: Long-term results of Phase III clinical trial. United States: N. p., 2006. Web. doi:10.1016/j.ijrobp.2006.05.026.
Skladowski, Krzysztof, Maciejewski, Boguslaw, Golen, Maria, Tarnawski, Rafal, Department of Radiobiology and Biostatistics, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice, Slosarek, Krzysztof, Suwinski, Rafal, Sygula, Mariusz, & Wygoda, Andrzej. Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: Long-term results of Phase III clinical trial. United States. doi:10.1016/j.ijrobp.2006.05.026.
Skladowski, Krzysztof, Maciejewski, Boguslaw, Golen, Maria, Tarnawski, Rafal, Department of Radiobiology and Biostatistics, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice, Slosarek, Krzysztof, Suwinski, Rafal, Sygula, Mariusz, and Wygoda, Andrzej. 2006. "Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: Long-term results of Phase III clinical trial". United States. doi:10.1016/j.ijrobp.2006.05.026.
@article{osti_20850154,
title = {Continuous accelerated 7-days-a-week radiotherapy for head-and-neck cancer: Long-term results of Phase III clinical trial},
author = {Skladowski, Krzysztof and Maciejewski, Boguslaw and Golen, Maria and Tarnawski, Rafal and Department of Radiobiology and Biostatistics, Center of Oncology-Maria Sklodowska-Curie Memorial Institute, Gliwice and Slosarek, Krzysztof and Suwinski, Rafal and Sygula, Mariusz and Wygoda, Andrzej},
abstractNote = {Purpose: To update 5-year results of a previously published study on special 7-days-a-week fractionation continuous accelerated irradiation (CAIR) for head-and-neck cancer patients. Methods and Materials: One hundred patients with squamous cell carcinoma of head and neck in Stage T{sub 2-4}N{sub 0-1}M were randomized between two definitive radiation treatments: accelerated fractionation 7 days a week including weekends (CAIR) and conventional 5 days a week (control). Hence the overall treatment time was 2 weeks shorter in CAIR. Results: Five-year local tumor control was 75% in the CAIR group and 33% in the control arm (p < 0.00004). Tumor-cure benefit corresponded with significant improvement in disease-free survival and overall survival rates. Confluent mucositis was the main acute toxicity, with the incidence significantly higher in CAIR patients than in control (respectively, 94% vs. 53%). When 2.0-Gy fractions were used, radiation necrosis developed in 5 patients (22%) in the CAIR group as a consequential late effect (CLE), but when fraction size was reduced to 1.8 Gy no more CLE occurred. Actuarial 5-year morbidity-free survival rate was similar for both treatments. Conclusions: Selected head-and-neck cancer patients could be treated very effectively with 7-days-a-week radiation schedule with no compromise of total dose and with slight 10% reduction of fraction dose (2 Gy-1.8 Gy), which article gives 1 week reduction of overall treatment time compared with standard 70 Gy in 35 fractions over 47-49 days. Although this report is based on the relatively small group of patients, its results have encouraged us to use CAIR fractionation in a standard radiation treatment for moderately advanced head-and-neck cancer patients.},
doi = {10.1016/j.ijrobp.2006.05.026},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 3,
volume = 66,
place = {United States},
year = 2006,
month =
}
  • Purpose: To report long-term results of randomized trial comparing 2 accelerated fractionations of definitive radiation therapy assessing the need to irradiate during weekend in patients with head and neck squamous cell carcinoma. Methods and Materials: A total of 345 patients with SCC of the oral cavity, larynx, and oro- or hypo-pharynx, stage T2-4N0-1M0, were randomized to receive continuous accelerated irradiation (CAIR: once per day, 7 days per week) or concomitant accelerated boost (CB: once per day, 3 days per week, and twice per day, 2 days per week). Total dose ranged from 66.6-72 Gy, dose per fraction was 1.8 Gy,more » number of fractions ranged from 37-40 fractions, and overall treatment time ranged from 37-40 days. Results: No differences for all trial end-points were noted. At 5 and 10 years, the actuarial rates of local-regional control were 63% and 60% for CAIR vs 65% and 60% for CB, and the corresponding overall survival were 40% and 25% vs 44% and 25%, respectively. Confluent mucositis was the main acute toxicity, with an incidence of 89% in CAIR and 86% in CB patients. The 5-year rate of grade 3-4 late radiation morbidity was 6% for both regimens. Conclusions: Results of this trial indicate that the effects of accelerated fractionation can be achieve by delivering twice-per-day irradiation on weekday(s). This trial has also confirmed that an accelerated, 6-weeks schedule is a reasonable option for patients with intermediate-stage head-and-neck squamous cell carcinoma because of the associated high cure rate and minimal severe late toxicity.« less
  • Purpose: To report the long-term results of the ARO 95-06 randomized trial comparing hyperfractionated accelerated chemoradiation with mitomycin C/5-fluorouracil (C-HART) with hyperfractionated accelerated radiation therapy (HART) alone in locally advanced head and neck cancer. Patients and Methods: The primary endpoint was locoregional control (LRC). Three hundred eighty-four patients with stage III (6%) and IV (94%) oropharyngeal (59.4%), hypopharyngeal (32.3%), and oral cavity (8.3%) cancer were randomly assigned to 30 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total of 70.6 Gy concurrently with mitomycin C/5-FU (C-HART) or 16 Gy/2 Gy daily followed by twice-daily 1.4 Gy to a total dose of 77.6 Gy alone (HART). Statisticalmore » analyses were done with the log-rank test and univariate and multivariate Cox regression analyses. Results: The median follow-up time was 8.7 years (95% confidence interval [CI]: 7.8-9.7 years). At 10 years, the LRC rates were 38.0% (C-HART) versus 26.0% (HART, P=.002). The cancer-specific survival and overall survival rates were 39% and 10% (C-HART) versus 30.0% and 9% (HART, P=.042 and P=.049), respectively. According to multivariate Cox regression analysis, the combined treatment was associated with improved LRC (hazard ratio [HR]: 0.6 [95% CI: 0.5-0.8; P=.002]). The association between combined treatment arm and increased LRC appeared to be limited to oropharyngeal cancer (P=.003) as compared with hypopharyngeal or oral cavity cancer (P=.264). Conclusions: C-HART remains superior to HART in terms of LRC. However, this effect may be limited to oropharyngeal cancer patients.« less
  • Purpose: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. Methods and Materials: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. Results: Compliance with the treatment protocol was high, with 87% of the patients receiving at least fivemore » cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. Conclusion: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.« less
  • Purpose: To determine the prognostic and predictive values of molecular marker expression profiles based on data from a randomized clinical trial of postoperative conventional fractionation (p-CF) therapy versus 7-day-per-week postoperative continuous accelerated irradiation (p-CAIR) therapy for squamous cell cancer of the head and neck. Methods and Materials: Tumor samples from 148 patients (72 p-CF and 76 p-CAIR patients) were available for molecular studies. Immunohistochemistry was used to assess levels of EGFR, nm23, Ki-67, p-53, and cyclin D1 expression. To evaluate the effect of fractionation relative to the expression profiles, data for locoregional tumor control (LRC) were analyzed using the Coxmore » proportional hazard regression model. Survival curves were compared using the Cox f test. Results: Patients who had tumors with low Ki-67, low p-53, and high EGFR expression levels and oral cavity/oropharyngeal primary cancer sites tended to benefit from p-CAIR. A joint score for the gain in LRC from p-CAIR based of these features was used to separate the patients into two groups: those who benefited significantly from p-CAIR with respect to LRC (n = 49 patients; 5-year LRC of 28% vs. 68%; p = 0.01) and those who did not benefit from p-CAIR (n = 99 patients; 5-year LRC of 72% vs. 66%; p = 0.38). The nm23 expression level appeared useful as a prognostic factor but not as a predictor of fractionation effect. Conclusions: These results support the studies that demonstrate the potential of molecular profiles to predict the benefit from accelerated radiotherapy. The molecular profile that favored accelerated treatment (low Ki-67, low p-53, and high EGFR expression) was in a good accordance with results provided by other investigators. Combining individual predictors in a joint score may improve their predictive potential.« less
  • Purpose: To prove an expected benefit of concurrent radiochemotherapy (RCT), a two-arm randomized multicentric study was performed. In a subgroup analysis the influence of pretherapeutical hemoglobin level (p-Hb) on survival under locoregional control (SLC) was tested. Patients and Methods: The study included primarily untreated Stage III/IV (International Union Against Cancer [UICC]) oropharyngeal and hypopharyngeal carcinomas. Patients were randomized to receive either hyperfractionated (hf) and accelerated (acc) RCT with two cycles 5-fluorouracil (600 mg/m{sup 2}/day) and carboplatin (70 mg/m{sup 2}/day) on Days 1-5 and 29-33 or hf-acc radiotherapy (RT) alone. Total RT dose in both arms was 69.9 Gy in 38more » days in concomitant boost technique. Results: After a median follow-up time of 57 months, SLC is significantly better in RCT than in RT (p = 0.01), with median SLC of 17 months and 11 months, respectively. Also overall survival (OS) shows a benefit for RCT (p 0.016), with a median survival of 23 months for RCT and 16 months for RT. However, the benefit in SLC and OS is not seen in hypopharyngeal carcinomas. In a multivariate analysis of oropharyngeal cancer patients, p-Hb levels lower than 12.7 g/dL resulted in lower SLC compared with higher p-Hb levels up to 13.8 g/dL. P-Hb levels >13.8 g/dL did not further improve SLC. Conclusions: Hyperfractionated-accelerated RCT is superior to hf-acc RT in oropharyngeal carcinomas. P-Hb levels >13.8 g/dL do not further improve SLC.« less