skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Predicting the Effect of Accelerated Fractionation in Postoperative Radiotherapy for Head and Neck Cancer Based on Molecular Marker Profiles: Data From a Randomized Clinical Trial

Abstract

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 Cox 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 ofmore » 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

Authors:
 [1]; ;  [2];  [1];  [3]; ;  [1];  [2]
  1. Department of Radiation Oncology, Center of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch (Poland)
  2. Department of Pathology, Center of Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice Branch (Poland)
  3. Department of Radiation Oncology, Regional Center of Oncology, Bydgoszcz (Poland)
Publication Date:
OSTI Identifier:
21372291
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 77; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2009.05.021; PII: S0360-3016(09)00769-X; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CLINICAL TRIALS; FRACTIONATED IRRADIATION; HEAD; NECK; NEOPLASMS; RADIOTHERAPY; SURVIVAL CURVES; BODY; DISEASES; IRRADIATION; MEDICINE; NUCLEAR MEDICINE; RADIOLOGY; TESTING; THERAPY

Citation Formats

Suwinski, Rafal, E-mail: rafals@io.gliwice.p, Jaworska, Magdalena, Nikiel, Barbara, Grzegorz, Wozniak, Bankowska-Wozniak, Magdalena, Wojciech, Majewski, Krzysztof, Skladowski, and Dariusz, Lange. Predicting the Effect of Accelerated Fractionation in Postoperative Radiotherapy for Head and Neck Cancer Based on Molecular Marker Profiles: Data From a Randomized Clinical Trial. United States: N. p., 2010. Web. doi:10.1016/j.ijrobp.2009.05.021.
Suwinski, Rafal, E-mail: rafals@io.gliwice.p, Jaworska, Magdalena, Nikiel, Barbara, Grzegorz, Wozniak, Bankowska-Wozniak, Magdalena, Wojciech, Majewski, Krzysztof, Skladowski, & Dariusz, Lange. Predicting the Effect of Accelerated Fractionation in Postoperative Radiotherapy for Head and Neck Cancer Based on Molecular Marker Profiles: Data From a Randomized Clinical Trial. United States. doi:10.1016/j.ijrobp.2009.05.021.
Suwinski, Rafal, E-mail: rafals@io.gliwice.p, Jaworska, Magdalena, Nikiel, Barbara, Grzegorz, Wozniak, Bankowska-Wozniak, Magdalena, Wojciech, Majewski, Krzysztof, Skladowski, and Dariusz, Lange. 2010. "Predicting the Effect of Accelerated Fractionation in Postoperative Radiotherapy for Head and Neck Cancer Based on Molecular Marker Profiles: Data From a Randomized Clinical Trial". United States. doi:10.1016/j.ijrobp.2009.05.021.
@article{osti_21372291,
title = {Predicting the Effect of Accelerated Fractionation in Postoperative Radiotherapy for Head and Neck Cancer Based on Molecular Marker Profiles: Data From a Randomized Clinical Trial},
author = {Suwinski, Rafal, E-mail: rafals@io.gliwice.p and Jaworska, Magdalena and Nikiel, Barbara and Grzegorz, Wozniak and Bankowska-Wozniak, Magdalena and Wojciech, Majewski and Krzysztof, Skladowski and Dariusz, Lange},
abstractNote = {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 Cox 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.},
doi = {10.1016/j.ijrobp.2009.05.021},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 77,
place = {United States},
year = 2010,
month = 6
}
  • Purpose: Based on our demonstration of a circadian rhythm in the human oral mucosa cell cycle, with most cells in the G{sub 1} phase in the morning and M phase at night, we hypothesized that morning radiotherapy (RT) would lead to less oral mucositis than afternoon RT. Methods and Materials: A total of 216 patients were randomized to morning (8-10 AM) vs. afternoon (4-6 PM) RT and stratified by radiation dose, smoking status, and center. Patients receiving primary or postoperative RT alone were eligible. Oral mucositis was scored using the Radiation Therapy Oncology Group (RTOG) criteria and a validated scoringmore » system. Results: Of 205 evaluable patients, 52.9% vs. 62.4% developed RTOG Grade 3 or greater mucositis after morning vs. afternoon RT, respectively (p = 0.17). Morning RT was also associated with significantly less weight loss after 5 months (p = 0.024). In a subgroup of 111 patients treated to a dose of 66-70 Gy in 33-35 fractions, exploratory analyses revealed a significant reduction in Grade 3 or greater mucositis with morning RT (44.6% vs. 67.3%, p = 0.022) and a longer interval to the development of Grade 3 or greater mucositis (median, >7.9 vs. 5.6 weeks, p = 0.033). In 53 patients, who smoked during therapy, a significant reduction was found in Grade 3 or greater mucositis with morning RT (42.9% vs. 76%, p = 0.025). Conclusion: In this proof of principle study, morning RT was associated with significantly less weight loss after 5 months and an apparent reduction in oral mucositis in a subset of patients receiving {>=}66 Gy and in patients who smoked during therapy.« less
  • 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 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
  • Purpose: To evaluate long-term late adverse events and treatment outcome of a randomized, multicenter Phase III trial of continuous, hyperfractionated, accelerated radiotherapy (CHART) compared with conventional radiotherapy (CRT) in 918 patients with advanced squamous cell carcinomas of the head and neck. Methods and Materials: Survival estimates were obtained for locoregional relapse-free survival, local relapse-free survival, overall survival, disease-specific survival, disease-free survival and for late adverse events. Results: The 10-year estimates (+-1 standard error) for locoregional relapse-free survival, overall survival, disease-free survival, and disease-specific survival were 43% +- 2% for CHART and 50% +- 3% with CRT (log-rank p = 0.2);more » 26% +- 2% and 29% +- 3% (p = 0.4), respectively; 41% +- 2% and 46% +- 3% (p = 0.3), respectively; and 56% +- 3% and 58% +- 3% (p = 0.5), respectively. There was a small but significant reduction in the incidence of slight or worse and moderate or worse epidermal adverse events with CHART (p = 0.002 to 0.05). Severe xerostomia, laryngeal edema, and mucosal necrosis were also significantly lower with CHART (p = 0.02 to 0.05). Conclusions: Despite the reduction in total dose from 66 Gy to 54 Gy, control of locoregional disease and survival with CHART were similar to those with CRT. These findings, together with the low incidence of long-term severe adverse events, suggest that CHART is a treatment option for patients with low-risk disease and for those unable to withstand the toxicity of concurrent chemoradiotherapy.« less
  • 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 significantmore » 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.« less