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Title: Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma

Abstract

Purpose: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. Methods and Materials: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n = 14), cisplatin plus FHX (n = 23), paclitaxel plus FHX (n = 42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n = 26), and irinotecan plus FHX (n = 10). Results: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%,more » respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. Conclusion: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials.« less

Authors:
 [1];  [1];  [2];  [2];  [1];  [1];  [1];  [3];  [2];  [1];  [4]
  1. Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States)
  2. (United States)
  3. Cancer Research Center, University of Chicago Pritzker School of Medicine, Chicago, IL (United States)
  4. Department of Radiation and Cellular Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL (United States) and Cancer Research Center, University of Chicago Pritzker School of Medicine, Chicago, IL (United States). E-mail: dharaf@radonc.uchicago.edu
Publication Date:
OSTI Identifier:
20793294
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 64; Journal Issue: 2; Other Information: DOI: 10.1016/j.ijrobp.2005.07.005; PII: S0360-3016(05)01165-X; 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; CHEMOTHERAPY; CLINICAL TRIALS; COMBINED THERAPY; HEAD; HEMORRHAGE; HYDROXYUREA; METASTASES; NECK; PATIENTS; RADIATION DOSES; SURGERY; TOXICITY; URACILS

Citation Formats

Salama, Joseph K., Vokes, Everett E., Section of Hematology/Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL, Cancer Research Center, University of Chicago Pritzker School of Medicine, Chicago, IL, Chmura, Steven J., Milano, Michael T., Kao, Johnny, Stenson, Kirsten M., Section of Otolaryngology/Head and Neck Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, Witt, Mary Ellyn R.N., and Haraf, Daniel J.. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. United States: N. p., 2006. Web. doi:10.1016/J.IJROBP.2005.0.
Salama, Joseph K., Vokes, Everett E., Section of Hematology/Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL, Cancer Research Center, University of Chicago Pritzker School of Medicine, Chicago, IL, Chmura, Steven J., Milano, Michael T., Kao, Johnny, Stenson, Kirsten M., Section of Otolaryngology/Head and Neck Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, Witt, Mary Ellyn R.N., & Haraf, Daniel J.. Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma. United States. doi:10.1016/J.IJROBP.2005.0.
Salama, Joseph K., Vokes, Everett E., Section of Hematology/Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL, Cancer Research Center, University of Chicago Pritzker School of Medicine, Chicago, IL, Chmura, Steven J., Milano, Michael T., Kao, Johnny, Stenson, Kirsten M., Section of Otolaryngology/Head and Neck Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL, Witt, Mary Ellyn R.N., and Haraf, Daniel J.. Wed . "Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20793294,
title = {Long-term outcome of concurrent chemotherapy and reirradiation for recurrent and second primary head-and-neck squamous cell carcinoma},
author = {Salama, Joseph K. and Vokes, Everett E. and Section of Hematology/Oncology, University of Chicago Pritzker School of Medicine, Chicago, IL and Cancer Research Center, University of Chicago Pritzker School of Medicine, Chicago, IL and Chmura, Steven J. and Milano, Michael T. and Kao, Johnny and Stenson, Kirsten M. and Section of Otolaryngology/Head and Neck Surgery, University of Chicago Pritzker School of Medicine, Chicago, IL and Witt, Mary Ellyn R.N. and Haraf, Daniel J.},
abstractNote = {Purpose: To define favorable pretreatment characteristics for overall survival (OS), progression-free survival (PFS), locoregional control, and freedom from distant metastasis for patients with recurrent and second primary head-and-neck cancer treated with concomitant chemotherapy and reirradiation. Methods and Materials: Our study population comprised a subset of 115 previously irradiated patients without overt metastases from 304 poor-prognosis head-and-neck cancer patients treated in seven consecutive phase I-II protocols. Of the 115 patients, 49, who had undergone surgical resection, were treated with a median of four cycles of concurrent chemotherapy and reirradiation and 66, who had not undergone surgical resection, were treated with a median of five cycles. The following regimens were used: 5-fluorouracil and hydroxyurea concurrent with reirradiation (FHX) (n = 14), cisplatin plus FHX (n = 23), paclitaxel plus FHX (n = 42), gemcitabine plus paclitaxel and 5-fluorouracil concurrent with reirradiation (n = 26), and irinotecan plus FHX (n = 10). Results: The median lifetime radiation dose was 131 Gy. The median follow-up for surviving patients was 67.4 months (range, 18.5-158.7). The median OS and PFS was 11 and 7 months (range, 0.2-158.7), respectively. The 3-year OS, PFS, locoregional control, and freedom from distant metastasis rate was 22%, 33%, 51%, and 61%, respectively. Multivariate analysis identified reirradiation dose, triple agent (cisplatin-, paclitaxel-, or gemcitabine-containing chemotherapy), and surgery before protocol treatment as independently prognostic for OS, PFS, and locoregional control. Triple-agent chemotherapy was prognostic for freedom from distant metastasis. Nineteen patients died of treatment-related toxicity, five of these of carotid hemorrhage. Conclusion: For recurrent and second primary head-and-neck cancer, trimodality therapy with surgery, concurrent chemotherapy, and reirradiation for a full second dose offers potential for long-term survival. Owing to the substantial toxicity and lack of an optimal regimen, reirradiation of recurrent head-and-neck cancer should be limited to clinical trials.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 2,
volume = 64,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2006},
month = {Wed Feb 01 00:00:00 EST 2006}
}
  • Purpose: Previous analysis of this Intergroup trial demonstrated that with a median follow-up among surviving patients of 45.9 months, the concurrent postoperative administration of cisplatin and radiation therapy improved local-regional control and disease-free survival of patients who had high-risk resectable head-and-neck carcinomas. With a minimum of 10 years of follow-up potentially now available for all patients, these results are updated here to examine long-term outcomes. Methods and Materials: A total of 410 analyzable patients who had high-risk resected head-and-neck cancers were prospectively randomized to receive either radiation therapy (RT: 60 Gy in 6 weeks) or identical RT plus cisplatin, 100more » mg/m{sup 2}i.v. on days 1, 22, and 43 (RT + CT). Results: At 10 years, the local-regional failure rates were 28.8% vs 22.3% (P=.10), disease-free survival was 19.1% vs 20.1% (P=.25), and overall survival was 27.0% vs 29.1% (P=.31) for patients treated by RT vs RT + CT, respectively. In the unplanned subset analysis limited to patients who had microscopically involved resection margins and/or extracapsular spread of disease, local-regional failure occurred in 33.1% vs 21.0% (P=.02), disease-free survival was 12.3% vs 18.4% (P=.05), and overall survival was 19.6% vs 27.1% (P=.07), respectively. Conclusion: At a median follow-up of 9.4 years for surviving patients, no significant differences in outcome were observed in the analysis of all randomized eligible patients. However, analysis of the subgroup of patients who had either microscopically involved resection margins and/or extracapsular spread of disease showed improved local-regional control and disease-free survival with concurrent administration of chemotherapy. The remaining subgroup of patients who were enrolled only because they had tumor in 2 or more lymph nodes did not benefit from the addition of CT to RT.« less
  • Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformalmore » RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54%, 31%, and 20% respectively. Conclusions: Continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin has an acceptable toxicity profile and offers a potentially curative option in a subset of patients with few other options.« less
  • Purpose: The aim of this study was to evaluate the efficacy of adjuvant radiotherapy after transoral laser microsurgery for advanced recurrent head-and-neck squamous cell carcinoma (HNSCC). Patients and Methods: Between 1988 and 2000, 37 patients with advanced local recurrences (23 local and 14 locoregional recurrences) of HNSCC without distant metastases were treated in curative intent with organ-preserving transoral laser microsurgery and adjuvant radiotherapy (before 1994 split-course radiotherapy with carboplatinum, after 1994 conventional radiotherapy). Initial therapy of the primary (8.1% oral cavity, 35.1% oropharynx, 13.5% hypopharynx, and 43.3% larynx) before relapse was organ-preserving transoral laser microsurgery without any adjuvant therapy. Results:more » After a median follow-up of 124 months, the 5-year overall survival rate was 21.3%, the loco-regional control rate 48.3%, respectively. In multivariate analysis, stage of original primary tumor (Stage I/II vs. Stage III/IV), and patient age (<58 years vs. {>=}58 years) showed statistically significant impact on prognosis. In laryngeal cancer, larynx preservation rate after treatment for recurrent tumor was 50% during follow-up. Conclusion: Our data show that organ-preserving transoral laser microsurgery followed by adjuvant radiotherapy is a curative option for patients who have advanced recurrence after transoral laser surgery and is an alternative to radical treatment.« less
  • Purpose: To examine the effects the proteasome inhibitor bortezomib (VELCADE) on transcription factor nuclear factor-{kappa}B (NF-{kappa}B) and target genes and the feasibility of combination therapy with reirradiation in patients with recurrent head-and-neck squamous cell carcinoma (HNSCC). Methods and Materials: The tolerability and response to bortezomib 0.6 mg/m{sup 2} and 0.9 mg/m{sup 2} given twice weekly concurrent with daily reirradiation to 50-70 Gy was explored. Blood proteasome inhibition and NF-{kappa}B-modulated cytokines and factors were measured. Proteasome inhibition, nuclear localization of NF-{kappa}B phospho-p65, apoptosis, and expression of NF-{kappa}B-modulated mRNAs were compared in serial biopsies from accessible tumors. Results: The maximally tolerated dosemore » was exceeded, and study was limited to 7 and 2 patients, respectively, given bortezomib 0.6 mg/m{sup 2} and 0.9 mg/m{sup 2}/dose with reirradiation. Grade 3 hypotension and hyponatremia were dose limiting. Mucositis was Grade 3 or less and was delayed. The mean blood proteasome inhibition at 1, 24, and 48 h after 0.6 mg/m{sup 2} was 32%, 16%, and 7% and after 0.9 mg/m{sup 2} was 56%, 26%, and 14%, respectively. Differences in proteasome and NF-{kappa}B activity, apoptosis, and expression of NF-{kappa}B-modulated cell cycle, apoptosis, and angiogenesis factor mRNAs were detected in 2 patients with minor tumor reductions and in serum NF-{kappa}B-modulated cytokines in 1 patient with a major tumor reduction. Conclusions: In combination with reirradiation, the maximally tolerated dose of bortezomib was exceeded at a dose of 0.6 mg/m{sup 2} and the threshold of proteasome inhibition. Although this regimen with reirradiation is not feasible, bortezomib induced detectable differences in NF-{kappa}B localization, apoptosis, and NF-{kappa}B-modulated genes and cytokines in tumor and serum in association with tumor reduction, indicating that other schedules of bortezomib combined with primary radiotherapy or reirradiation may merit future investigation.« less
  • Purpose: To report our experience with a prospective protocol of external beam reirradiation (Re-RT) combined with cetuximab for patients with inoperable, recurrent squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Between August 2008 and June 2010, 18 patients with inoperable recurrence of SCCHN after adjuvant or definitive radiotherapy (RT) and simultaneous or sequential cisplatin-based chemotherapy for primary SCCHN were enrolled. Acute and late toxicity from the experimental regimen were recorded every week during RT and every 3 months thereafter. Efficacy was assessed with repeated imaging using response evaluation criteria in solid tumors and clinical examinations 8-12more » weeks after completion of the treatment and every 3 months thereafter. Results: Median follow-up time for all patients was 9.4 (range: 3.85-31.7) months and for patients alive 30.4 (range: 15.7-31.7) months. Acute toxicity was generally mild or moderate. Five patients developed a grade 3 acneiform rash related to cetuximab. Late toxicity occurred as grade 3 trismus in five and as grade 3 abacterial salivary gland inflammation in one patient, respectively. Overall response rate was 47%. Median overall and progression-free survival for all patients was 8.38 months and 7.33 months, respectively. The overall survival rate was 44% at 1 year, with a 1 year local control rate of 33%. Conclusion: Notwithstanding the limitations of our preliminary data Re-RT combined with cetuximab for recurrent and inoperable SCCHN is feasible and the integration of newer targeted agents seems to be less toxic compared to conventional chemotherapy with encouraging response rates at least for a subset of patients.« less