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Title: Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer

Abstract

Introduction: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. Subjects: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m{sup 2} on Day 1 and 5-FU 1,000 mg/m{sup 2}/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m{sup 2} on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed onmore » patients with persistent or recurrent disease. Methods: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months. Results: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09). Conclusions: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.« less

Authors:
 [1];  [2];  [3];  [4];  [4];  [4];  [4];  [3];  [5];  [5];  [5];  [5];  [5]
  1. Head and Neck Oncology Program, University of Michigan, Ann Arbor, MI (United States). E-mail: kevin.fung@lhsc.on.ca
  2. Speech-Language Pathology Program, Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI (United States)
  3. Department of Biostatistics, University of Michigan, Ann Arbor, MI (United States)
  4. Department of Internal Medicine, Division of Hematology, University of Michigan, Ann Arbor, MI (United States)
  5. Head and Neck Oncology Program, University of Michigan, Ann Arbor, MI (United States)
Publication Date:
OSTI Identifier:
20788231
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 63; Journal Issue: 5; Other Information: DOI: 10.1016/j.ijrobp.2005.05.004; PII: S0360-3016(05)00812-6; Copyright (c) 2005 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; BIOPSY; CARCINOMAS; CHEMOTHERAPY; CLINICAL TRIALS; COMBINED THERAPY; HEAD; INTAKE; LARYNGECTOMY; LARYNX; NECK; NUTRITION; PATIENTS; PRESERVATION; RADIOTHERAPY; SPEECH; TOXICITY

Citation Formats

Fung, Kevin, Lyden, Teresa H., Lee, Julia, Urba, Susan G., Worden, Frank, Eisbruch, Avraham, Tsien, Christina, Bradford, Carol R., Chepeha, Douglas B., Hogikyan, Norman D., Prince, Mark E.P., Teknos, Theodoros N., and Wolf, Gregory T. Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer. United States: N. p., 2005. Web. doi:10.1016/J.IJROBP.2005.0.
Fung, Kevin, Lyden, Teresa H., Lee, Julia, Urba, Susan G., Worden, Frank, Eisbruch, Avraham, Tsien, Christina, Bradford, Carol R., Chepeha, Douglas B., Hogikyan, Norman D., Prince, Mark E.P., Teknos, Theodoros N., & Wolf, Gregory T. Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer. United States. doi:10.1016/J.IJROBP.2005.0.
Fung, Kevin, Lyden, Teresa H., Lee, Julia, Urba, Susan G., Worden, Frank, Eisbruch, Avraham, Tsien, Christina, Bradford, Carol R., Chepeha, Douglas B., Hogikyan, Norman D., Prince, Mark E.P., Teknos, Theodoros N., and Wolf, Gregory T. Thu . "Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer". United States. doi:10.1016/J.IJROBP.2005.0.
@article{osti_20788231,
title = {Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer},
author = {Fung, Kevin and Lyden, Teresa H. and Lee, Julia and Urba, Susan G. and Worden, Frank and Eisbruch, Avraham and Tsien, Christina and Bradford, Carol R. and Chepeha, Douglas B. and Hogikyan, Norman D. and Prince, Mark E.P. and Teknos, Theodoros N. and Wolf, Gregory T.},
abstractNote = {Introduction: Organ-preservation treatment approaches for advanced laryngeal cancer patients that use combination chemoradiotherapy result in cure rates similar to primary laryngectomy with postoperative radiotherapy. In the national VA Larynx Cancer Trial, successful organ preservation was associated with an overall improvement in quality of life but not in subjective speech compared with long-term laryngectomy survivors. As part of a Phase II clinical trial, a prospective study of speech and swallowing results was conducted to determine if larynx preservation is associated with improved voice and swallowing compared with results in patients who require salvage laryngectomy. Subjects: A total of 97 patients with advanced laryngeal cancer (46 Stage III, 51 Stage IV) were given a single course of induction chemotherapy (cisplatin 100 mg/m{sup 2} on Day 1 and 5-FU 1,000 mg/m{sup 2}/day x 5 days), followed by assessment of response. Patients with less than 50% response underwent early salvage laryngectomy, and patients with 50% or better response underwent concurrent chemoradiation (72 Gy and cisplatin 100 mg/m{sup 2} on Days 1, 22, and 43), followed by two cycles of adjuvant chemotherapy (DDP/5-FU). Direct laryngoscopy and biopsy were performed 8 weeks after radiation therapy to determine final tumor response. Late salvage surgery was performed on patients with persistent or recurrent disease. Methods: Completed survey data on voice and swallowing utilizing the Voice-Related Quality of Life Measure (V-RQOL) and the List Performance Status Scale for Head and Neck Cancer Patients (PSS-HN) were obtained from 56 patients who were alive and free of disease at the time of survey, with a minimum follow-up of 8 months. Comparisons were made between patients with an intact larynx (n = 37) vs. laryngectomy (n = 19), as well as early (n = 12) vs. late salvage laryngectomy (n = 7). Multivariate analysis was performed to determine factors predictive of voice and swallowing outcomes. Overall 3-year determinant survival was 87%, with median follow-up of 40 months. Results: Patients with an intact larynx demonstrated significantly higher (p = 0.02) mean V-RQOL scores (80.3) than did laryngectomy patients (65.4). This finding was consistent in the social-emotional (p = 0.007) and physical functioning domains (p = 0.03). No differences in V-RQOL scores were found in comparisons between early and late salvage laryngectomy. Multiple linear regression revealed that predictors of higher total V-RQOL scores include lower T stage (p = 0.03), organ preservation (p = 0.0007), and longer duration since treatment (p = 0.01). Understandability of speech was better in patients with an intact larynx (p = 0.001). Overall swallowing function was comparable between groups. Multiple logistic regression revealed that longer duration since treatment (p = 0.03, odds ratio = 1.1) and lower maximal mucositis grade (p = 0.03, odds ratio = 0.3) were predictive of higher likelihood of eating in public. Nutritional mode consisting of oral intake alone without nutritional supplements was achieved in 88.9% of patients with an intact larynx compared with 64.3% of laryngectomees (p = 0.09). Conclusions: Voice-related quality of life is better in patients after chemoradiation therapy compared with salvage laryngectomy. Earlier salvage, although known to be associated with fewer surgical complications, did not result in improved voice; however, the number of patients analyzed is small. Overall swallowing function is good in all patients; however, patients with an intact larynx are more likely to obtain nutrition with oral intake alone without supplements. Such measures of function and quality of life are important endpoints to help judge overall effectiveness as newer, more aggressive treatment protocols with added toxicities are developed and evaluated.},
doi = {10.1016/J.IJROBP.2005.0},
journal = {International Journal of Radiation Oncology, Biology and Physics},
number = 5,
volume = 63,
place = {United States},
year = {Thu Dec 01 00:00:00 EST 2005},
month = {Thu Dec 01 00:00:00 EST 2005}
}
  • Purpose: To determine the rates of organ preservation and function in patients with advanced laryngeal and hypopharyngeal carcinomas treated with concurrent chemoradiotherapy (CRT). Methods and Materials: Between April 1999 and September 2005, 82 patients with advanced laryngeal (67%) and hypopharyngeal carcinomas (33%) underwent conventional radiotherapy and concurrent platinum-based chemotherapy with curative intent. Sixty-two patients were male (75.6%). The median age was 59 years. Eighteen patients (22%) were in Stage III and 64 (78%) were in Stage IV. The median radiation dose was 70 Gy. The median potential follow-up was 3.9 years. Results: Overall survival and disease-free survival were respectively 63%more » and 73% at 3 years. Complete response rate from CRT was 75%. Nineteen patients (23%) experienced significant long-term toxicity after CRT: 6 (7.3%) required a percutaneous endoscopic gastrostomy, 5 (6%) had persistent Grade 2 or 3 dysphagia, 2 (2.4%) had pharyngoesophageal stenosis requiring multiple dilations, 2 (2.4%) had chronic lung aspiration, and 7 (8.5%) required a permanent tracheostomy. Four patients (4.9%) underwent laryngectomy without pathologic evidence of disease. At last follow-up, 5 (6%) patients were still dependent on a gastrostomy. Overall, 42 patients (52%) were alive, in complete response, with a functional larynx and no other major complications. Conclusions: In our institution, CRT for advanced hypopharyngeal and laryngeal carcinoma has provided good overall survival and locoregional control in the majority of patients, but a significant proportion did not benefit from this approach because of either locoregional failure or late complications. Better organ preservation approaches are necessary to improve locoregional control and to reduce long-term toxicities.« less
  • Purpose: To conduct prospective electroglottographic analyses of voice outcomes after radical chemoradiotherapy for locally advanced laryngopharyngeal cancers and to compare them with patients who have undergone total laryngectomy (TL). Patients and Methods: Twenty-one patients (19 male, 2 female, median age [range] 65 [50-85] years) with Stage III/IV laryngopharyngeal cancer received induction chemotherapy followed by radical chemoradiotherapy. Electroglottography, using the sustained vowel /i/ and connected speech, was performed before treatment and 1, 6, and 12 months after treatment. In addition, single voice recordings were taken from 21 patients (16 male, 5 female, aged 65 [50-84] years) who had undergone TL andmore » surgical voice restoration and from 21 normal controls (18 male, 3 female, aged 65 [33-80] years). Results: Before treatment the vocal measures for the chemoradiotherapy patients were significantly different from normal controls in jitter (p = 0.02), maximum phonation time (MPT) (p = 0.001), and words per minute (WPM) (p = 0.01). At 12 months after treatment MPT and WPM had normalized, but jitter and normalized noise energy were significantly worse than in normal controls. Comparison of voice outcomes at 12 months for chemoradiotherapy patients revealed superiority over the TL group in all parameters except MPT (18.2 s vs. 10.4 s, p = 0.06). Analysis of the recovery of voice up to 12 months after treatment revealed progressive improvement in most electroglottographic measures. Conclusions: This prospective study demonstrates significantly better outcome for patients treated with chemoradiotherapy as compared with TL. Progressive normalization of many voice parameters occurs over the 12 months following chemoradiotherapy.« less
  • Purpose: To investigate, in rectal cancer, the benefit of a neoadjuvant radiation dose escalation with endocavitary contact radiotherapy (CXRT) in addition to external beam radiotherapy (EBRT). This article provides an update of the Lyon R96-02 Phase III trial. Methods and Materials: A total of 88 patients with T2 to T3 carcinoma of the lower rectum were randomly assigned to neoadjuvant EBRT 39 Gy in 13 fractions (43 patients) vs. the same EBRT with CXRT boost, 85 Gy in three fractions (45 patients). Median follow-up was 132 months. Results: The 10-year cumulated rate of permanent colostomy (CRPC) was 63% in themore » EBRT group vs. 29% in the EBRT+CXRT group (p < 0.001). The 10-year rate of local recurrence was 15% vs. 10% (p = 0.69); 10-year disease-free survival was 54% vs. 53% (p = 0.99); and 10-year overall survival was 56% vs. 55% (p = 0.85). Data of clinical response (CR) were available for 78 patients (36 in the EBRT group and 42 in the EBRT+CXRT group): 12 patients were in complete CR (1 patient vs. 11 patients), 53 patients had a CR {>=}50% (24 patients vs. 29 patients), and 13 patients had a CR <50% (11 patients vs. 2 patients) (p < 0.001). Of the 65 patients with CR {>=}50%, 9 had an organ preservation procedure (meaning no rectal resection) taking advantage of major CR. The 10-year CRPC was 17% for patients with complete CR, 42% for patients with CR {>=}50%, and 77% for patients with CR <50% (p = 0.014). Conclusion: In cancer of the lower rectum, CXRT increases the complete CR, turning in a significantly higher rate of long-term permanent sphincter and organ preservation.« less
  • Purpose: Concomitant treatment with radiation therapy and cisplatin (CDDP) remains the gold standard for bladder preservation in the treatment of muscle-invasive bladder cancer (MIBC). We present the long-term results of a phase 1 clinical trial to assess the association of twice-weekly gemcitabine with CDDP and radiation therapy in this setting. Methods and Materials: Patients with pT2-pT4N0M0 MIBC without hydronephrosis or diffuse carcinoma in situ were enrolled in this study. After maximal transurethral resection of the bladder tumor, patients received concomitant radiation therapy (63 Gy in 1.8 fractions) and chemotherapy (CDDP 20 mg/m²/day over 4 days every 21 days and gemcitabinemore » twice a week). The starting dose of gemcitabine was 15 mg/m² with dose escalation to 20, 25, and 30 mg/m². The primary endpoint was the maximum tolerated dose (MTD). Secondary endpoints included toxicity and tumor control. Results: Fourteen patients were enrolled. Dose-limiting toxicity occurred in 2 patients treated with 30 mg/m² gemcitabine (grade 4 thrombocytopenia and severe impairment of World Health Organization performance status, respectively). Nine patients received the complete chemoradiation therapy protocol. The recommended dose of gemcitabine was 25 mg/m². The median follow-up time was 53 months, and the overall and disease-specific 5-year survival rates were 62% and 77%, respectively. Among the patients who received the complete treatment, bladder-intact survival was 76% at 5 years, and the median overall survival was 69.6 months. Conclusions: This regimen was well tolerated. The gemcitabine MTD was 25 mg/m². Bladder preservation and disease control were promising. A multicenter phase 2 randomized trial is ongoing.« less
  • Purpose: To analyze dosimetric variables and outcomes after adaptive replanning of radiation therapy during concurrent high-dose protons and chemotherapy for locally advanced non-small cell lung cancer (NSCLC). Methods and Materials: Nine of 44 patients with stage III NSCLC in a prospective phase II trial of concurrent paclitaxel/carboplatin with proton radiation [74 Gy(RBE) in 37 fractions] had modifications to their original treatment plans after re-evaluation revealed changes that would compromise coverage of the target volume or violate dose constraints; plans for the other 35 patients were not changed. We compared patients with adaptive plans with those with nonadaptive plans in termsmore » of dosimetry and outcomes. Results: At a median follow-up of 21.2 months (median overall survival, 29.6 months), no differences were found in local, regional, or distant failure or overall survival between groups. Adaptive planning was used more often for large tumors that shrank to a greater extent (median, 107.1 cm{sup 3} adaptive and 86.4 cm{sup 3} nonadaptive; median changes in volume, 25.3% adaptive and 1.2% nonadaptive; P<.01). The median number of fractions delivered using adaptive planning was 13 (range, 4-22). Adaptive planning generally improved sparing of the esophagus (median absolute decrease in V{sub 70}, 1.8%; range, 0%-22.9%) and spinal cord (median absolute change in maximum dose, 3.7 Gy; range, 0-13.8 Gy). Without adaptive replanning, target coverage would have been compromised in 2 cases (57% and 82% coverage without adaptation vs 100% for both with adaptation); neither patient experienced local failure. Radiation-related grade 3 toxicity rates were similar between groups. Conclusions: Adaptive planning can reduce normal tissue doses and prevent target misses, particularly for patients with large tumors that shrink substantially during therapy. Adaptive plans seem to have acceptable toxicity and achieve similar local, regional, and distant control and overall survival, even in patients with larger tumors, vs nonadaptive plans.« less