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

Title: Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience

Abstract

Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HRmore » 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.« less

Authors:
 [1];  [2];  [3];  [1];  [4];  [5];  [6];  [4];  [7];  [8];  [9];  [10];  [11];  [2];  [12]
  1. Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania (United States)
  2. NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania (United States)
  3. University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin (United States)
  4. University of Texas M. D. Anderson Cancer Center, Houston, Texas (United States)
  5. H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida (United States)
  6. Radiological Associates of Sacramento, Sacramento, California (United States)
  7. Virginia Mason Medical Center, Seattle, Washington (United States)
  8. Mayo Clinic, Rochester, Minnesota (United States)
  9. University of Colorado Comprehensive Cancer Center, Denver, Colorado (United States)
  10. McGill University, Montreal, Quebec (Canada)
  11. University of Alabama at Birmingham, Birmingham, Alabama (United States)
  12. Stanford University Medical Center, Stanford, California (United States)
Publication Date:
OSTI Identifier:
22648753
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 95; Journal Issue: 5; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The 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; CHEMOTHERAPY; CORRELATIONS; DERMATITIS; GY RANGE 10-100; HEAD; NECK; NEOPLASMS; PATIENTS; RADIOTHERAPY; SKIN

Citation Formats

Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu, Zhang, Qiang, Harari, Paul M., Axelrod, Rita, Rosenthal, David I., Trotti, Andy, Jones, Christopher U., Garden, Adam S., Song, Guobin, Foote, Robert L., Raben, David, Shenouda, George, Spencer, Sharon A., Harris, Jonathan, and Le, Quynh-Thu. Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience. United States: N. p., 2016. Web. doi:10.1016/J.IJROBP.2016.03.011.
Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu, Zhang, Qiang, Harari, Paul M., Axelrod, Rita, Rosenthal, David I., Trotti, Andy, Jones, Christopher U., Garden, Adam S., Song, Guobin, Foote, Robert L., Raben, David, Shenouda, George, Spencer, Sharon A., Harris, Jonathan, & Le, Quynh-Thu. Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience. United States. doi:10.1016/J.IJROBP.2016.03.011.
Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu, Zhang, Qiang, Harari, Paul M., Axelrod, Rita, Rosenthal, David I., Trotti, Andy, Jones, Christopher U., Garden, Adam S., Song, Guobin, Foote, Robert L., Raben, David, Shenouda, George, Spencer, Sharon A., Harris, Jonathan, and Le, Quynh-Thu. Mon . "Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience". United States. doi:10.1016/J.IJROBP.2016.03.011.
@article{osti_22648753,
title = {Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience},
author = {Bar-Ad, Voichita, E-mail: voichita.bar-ad@jefferson.edu and Zhang, Qiang and Harari, Paul M. and Axelrod, Rita and Rosenthal, David I. and Trotti, Andy and Jones, Christopher U. and Garden, Adam S. and Song, Guobin and Foote, Robert L. and Raben, David and Shenouda, George and Spencer, Sharon A. and Harris, Jonathan and Le, Quynh-Thu},
abstractNote = {Purpose: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab. Methods and Materials: Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin). Results: Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002). Conclusion: Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.},
doi = {10.1016/J.IJROBP.2016.03.011},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 95,
place = {United States},
year = {Mon Aug 01 00:00:00 EDT 2016},
month = {Mon Aug 01 00:00:00 EDT 2016}
}
  • The purpose of this study was (1) to evaluate dose to skin between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) treatment techniques for target sites in the head and neck, pelvis, and brain and (2) to determine if the treatment dose and fractionation regimen affect the skin dose between traditional sequential boost and integrated boost regimens for patients with head and neck cancer. A total of 19 patients and 48 plans were evaluated. The Eclipse (v11) treatment planning system was used to plan therapy in 9 patients with head and neck cancer, 5 patients with prostate cancer, andmore » 5 patients with brain cancer with VMAT and static-field IMRT. The mean skin dose and the maximum dose to a contiguous volume of 2 cm{sup 3} for head and neck plans and brain plans and a contiguous volume of 5 cm{sup 3} for pelvis plans were compared for each treatment technique. Of the 9 patients with head and neck cancer, 3 underwent an integrated boost regimen. One integrated boost plan was replanned with IMRT and VMAT using a traditional boost regimen. For target sites located in the head and neck, VMAT reduced the mean dose and contiguous hot spot most noticeably in the shoulder region by 5.6% and 5.4%, respectively. When using an integrated boost regimen, the contiguous hot spot skin dose in the shoulder was larger on average than a traditional boost pattern by 26.5% and the mean skin dose was larger by 1.7%. VMAT techniques largely decrease the contiguous hot spot in the skin in the pelvis by an average of 36% compared with IMRT. For the same target coverage, VMAT can reduce the skin dose in all the regions of the body, but more noticeably in the shoulders in patients with head and neck and pelvis cancer. We also found that using integrated boost regimens in patients with head and neck cancer leads to higher shoulder skin doses compared with traditional boost regimens.« less
  • One hundred outpatients with proved advanced epidermoid carcinoma of the head and neck underwent complete treatment with concomitant hydroxyurea and irradiation therapy. Seventy-three patients exhibited complete regression of the tumor. All patients became candidates for operation after completion of combination therapy, although not all patients accepted surgery.
  • Purpose: To assess the rate of serious (>Grade 2, CTCAE 3.0) dermatitis in our head-and-neck cancer (HNC) patients undergoing simultaneous integrated boost intensity-modulated radiotherapy with concomitant cetuximab (SIB-IMRT-cetuximab). We hypothesized a positive association between the radiation dose to the skin and the degree of dermatitis in patients receiving cetuximab. Methods and Materials: Between April 2006 and December 2009, 99 HNC patients underwent SIB-IMRT-cetuximab. In 69/99 (70%), systemic treatment consisted of concomitant cetuximab only, whereas 30 (30%) were switched from concomitant cisplatin to concomitant cetuximab. Treatment-related dermatitis was prospectively monitored. Ninety-nine patients treated with four to seven concomitant cycles of cisplatinmore » only served as an internal control group. The radiation dose delivered to the skin was measured and related to dermal reactions. Results: Grade 3/4 dermatitis developed in 34% of the cetuximab cohort, which was substantially higher than in the control cohort (3%, p < 0.01). No cases of skin necrosis or other fatal events related to cetuximab have occurred so far. A significantly larger mean skin area was found exposed to high radiation doses in patients with severe cetuximab-related dermatitis, compared with those without (p < 0.01). Conclusion: Concomitant cetuximab resulted in a {approx}10-fold increase in the rate of severe transient dermatitis compared with the use of concomitant cisplatin. We found a positive association between the incidence of Grade 3/4 dermatitis and the radiation dose delivered to the skin in patients receiving cetuximab.« less
  • Purpose: Report of clinical cancer control outcomes on Radiation Therapy Oncology Group (RTOG) 9406, a three-dimensional conformal radiation therapy (3D-CRT) dose escalation trial for localized adenocarcinoma of the prostate. Methods and Materials: RTOG 9406 is a Phase I/II multi-institutional dose escalation study of 3D-CRT for men with localized prostate cancer. Patients were registered on five sequential dose levels: 68.4 Gy, 73.8 Gy, 79.2 Gy, 74 Gy, and 78 Gy with 1.8 Gy/day (levels I-III) or 2.0 Gy/day (levels IV and V). Neoadjuvant hormone therapy (NHT) from 2 to 6 months was allowed. Protocol-specific, American Society for Therapeutic Radiation Oncology (ASTRO),more » and Phoenix biochemical failure definitions are reported. Results: Thirty-four institutions enrolled 1,084 patients and 1,051 patients are analyzable. Median follow-up for levels I, II, III, IV, and V was 11.7, 10.4, 11.8, 10.4, and 9.2 years, respectively. Thirty-six percent of patients received NHT. The 5-year overall survival was 90%, 87%, 88%, 89%, and 88% for dose levels I-V, respectively. The 5-year clinical disease-free survival (excluding protocol prostate-specific antigen definition) for levels I-V is 84%, 78%, 81%, 82%, and 82%, respectively. By ASTRO definition, the 5-year disease-free survivals were 57%, 59%, 52%, 64% and 75% (low risk); 46%, 52%, 54%, 56%, and 63% (intermediate risk); and 50%, 34%, 46%, 34%, and 61% (high risk) for levels I-V, respectively. By the Phoenix definition, the 5-year disease-free survivals were 68%, 73%, 67%, 84%, and 80% (low risk); 70%, 62%, 70%, 74%, and 69% (intermediate risk); and 42%, 62%, 68%, 54%, and 67% (high risk) for levels I-V, respectively. Conclusion: Dose-escalated 3D-CRT yields favorable outcomes for localized prostate cancer. This multi-institutional experience allows comparison to other experiences with modern radiation therapy.« less
  • Purpose: To compare the M. D. Anderson Symptom Inventory-Head and Neck (MDASI-HN) module, a symptom burden instrument, with the Functional Assessment of Cancer Therapy-Head and Neck (FACT-HN) module, a quality-of-life instrument, for the assessment of mucositis in patients with head-and-neck cancer treated with radiotherapy and to identify the most distressing symptoms from the patient's perspective. Methods and Materials: Consecutive patients with head-and-neck cancer (n = 134) completed the MDASI-HN and FACT-HN before radiotherapy (time 1) and after 6 weeks of radiotherapy or chemoradiotherapy (time 2). The mean global and subscale scores for each instrument were compared with the objective mucositismore » scores determined from the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Results: The global and subscale scores for each instrument showed highly significant changes from time 1 to time 2 and a significant correlation with the objective mucositis scores at time 2. Only the MDASI scores, however, were significant predictors of objective Common Terminology Criteria for Adverse Events mucositis scores on multivariate regression analysis (standardized regression coefficient, 0.355 for the global score and 0.310 for the head-and-neck cancer-specific score). Most of the moderate and severe symptoms associated with mucositis as identified on the MDASI-HN are not present on the FACT-HN. Conclusion: Both the MDASI-HN and FACT-HN modules can predict the mucositis scores. However, the MDASI-HN, a symptom burden instrument, was more closely associated with the severity of radiation-induced mucositis than the FACT-HN on multivariate regression analysis. This greater association was most likely related to the inclusion of a greater number of face-valid mucositis-related items in the MDASI-HN compared with the FACT-HN.« less