Subjective voice quality, communicative ability and swallowing after definitive radio(chemo)therapy, laryngectomy plus radio(chemo)therapy, or organ conservation surgery plus radio(chemo)therapy for laryngeal and hypopharyngeal cancer

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Abstract

This retrospective analysis focusses on the impact of therapy on perceived long-term post-cancer treatment function. A validated questionnaire including items and components for the assessment of communicative ability, quality of voice and swallowing was sent to 129 patients. All patients were treated between 1998 and 2007. A total of 76 patients (58.9%) with carcinoma of the larynx or hypopharynx replied to the questionnaire. Data was evaluated retrospectively. Therapy delivered was definitive radio(chemo)therapy (defchRT/RT) (21/76, 28%), laryngectomy + radio(chemo)therapy (LE + chRT/RT) (28/76, 37%), or larynx conservation surgery + radio(chemo)therapy (LCS + chRT/RT) (27/76, 36%). Radiotherapy was administered using 2D- or 3D-conformal planning. The most common concomitant chemotherapy delivered was cisplatin + 5FU. For statistical analyses of the components, averages were calculated and tested using the Kruskal–Wallis test and the U-test of Mann and Whitney. Differences were assessed by the Monte Carlo method or Fisher's exact test. The single item rates were compared with Fisher's exact test. Mean follow-up was 56.7 months (range, 8–130 months). After defchRT/RT, patients trended towards more substantial–strong hoarseness compared with LCS + chRT/RT ( P = 0.2). After LE, patients were dissatisfied with their artificial larynx/electrolarynx and the tone of their voice ( P = 0.3, P = 0.07) and communicative ability ( P = 0.005, P = 0.008) compared with those treated with defchRT/RT and LCS + chRT/RT, respectively. Dysphagia and additional percutaneous endoscopic gastrostomy (PEG) feeding were more frequent after defchRT/RT in comparison with the other two groups ( P < 0.05). Voice quality and communicative ability were slightly worse after defchRT/RT and LE + chRT/RT, but satisfying with all treatment modalities. Further development of the therapy approach is necessary to reduce long-term side effects, with measures of post-treatment function as important endpoints.

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Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group.

Gregory Wolf, Susan Gross Fisher, Waun Hong … (1991)

We performed a prospective, randomized study in patients with previously untreated advanced (Stage III or IV) laryngeal squamous carcinoma to compare the results of induction chemotherapy followed by definitive radiation therapy with those of conventional laryngectomy and postoperative radiation. Three hundred thirty-two patients were randomly assigned to receive either three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy. The clinical tumor response was assessed after two cycles of chemotherapy, and patients with a response received a third cycle followed by definitive radiation therapy (6600 to 7600 cGy). Patients in whom ther was no tumor response or who had locally recurrent cancers after chemotherapy and radiation therapy underwent salvage laryngectomy. After two cycles of chemotherapy, the clinical tumor response was complete in 31 percent of the patients and partial in 54 percent. After a median follow-up of 33 months, the estimated 2-year survival was 68 percent (95 percent confidence interval, 60 to 76 percent) for both treatment groups (P = 0.9846). Patterns of recurrence differed significantly between the two groups, with more local recurrences (P = 0.0005) and fewer distant metastases (P = 0.016) in the chemotherapy group than in the surgery group. A total of 59 patients in the chemotherapy group (36 percent) required total laryngectomy. The larynx was preserved in 64 percent of the patients overall and 64 percent of the patients who were alive and free of disease. These preliminary results suggest a new role for chemotherapy in patients with advanced laryngeal cancer and indicate that a treatment strategy involving induction chemotherapy and definitive radiation therapy can be effective in preserving the larynx in a high percentage of patients, without compromising overall survival.

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Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

Arlene Forastiere, Qiang Zhang, Randal Weber … (2013)

To report the long-term results of the Intergroup Radiation Therapy Oncology Group 91-11 study evaluating the contribution of chemotherapy added to radiation therapy (RT) for larynx preservation. Patients with stage III or IV glottic or supraglottic squamous cell cancer were randomly assigned to induction cisplatin/fluorouracil (PF) followed by RT (control arm), concomitant cisplatin/RT, or RT alone. The composite end point of laryngectomy-free survival (LFS) was the primary end point. Five hundred twenty patients were analyzed. Median follow-up for surviving patients is 10.8 years. Both chemotherapy regimens significantly improved LFS compared with RT alone (induction chemotherapy v RT alone: hazard ratio [HR], 0.75; 95% CI, 0.59 to 0.95; P = .02; concomitant chemotherapy v RT alone: HR, 0.78; 95% CI, 0.78 to 0.98; P = .03). Overall survival did not differ significantly, although there was a possibility of worse outcome with concomitant relative to induction chemotherapy (HR, 1.25; 95% CI, 0.98 to 1.61; P = .08). Concomitant cisplatin/RT significantly improved the larynx preservation rate over induction PF followed by RT (HR, 0.58; 95% CI, 0.37 to 0.89; P = .0050) and over RT alone (P < .001), whereas induction PF followed by RT was not better than treatment with RT alone (HR, 1.26; 95% CI, 0.88 to 1.82; P = .35). No difference in late effects was detected, but deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% v 20.8% with induction chemotherapy and 16.9% with RT alone). These 10-year results show that induction PF followed by RT and concomitant cisplatin/RT show similar efficacy for the composite end point of LFS. Locoregional control and larynx preservation were significantly improved with concomitant cisplatin/RT compared with the induction arm or RT alone. New strategies that improve organ preservation and function with less morbidity are needed.

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Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?

Avraham Eisbruch, Marco Schwartz, Coen Rasch … (2004)

To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT. A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer. The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose. The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.

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Author and article information

Journal

Journal ID (nlm-ta): J Radiat Res

Journal ID (iso-abbrev): J. Radiat. Res

Journal ID (publisher-id): jrr

Journal ID (hwp): jrr

Title: Journal of Radiation Research

Publisher: Oxford University Press

ISSN (Print): 0449-3060

ISSN (Electronic): 1349-9157

Publication date (Print): January 2015

Publication date (Electronic): 26 October 2014

Publication date PMC-release: 26 October 2014

Volume: 56

Issue: 1

Pages: 159-168

Affiliations

[1 ]Department of Radiotherapy, University of Rostock , Südring 75, 18059 Rostock, Germany

[2 ]Department of Radiotherapy, University of Leipzig , Stephanstraße 9a, 04103 Leipzig, Germany

[3 ]Department of Otolaryngology, Head and Neck Surgery ‘Otto Körner’, University of Rostock , Doberaner Straße 137–139, 18057 Rostock, Germany

[4 ]Department of Radiation Oncology, Hospital Chemnitz , Bürgerstraße 2, 09113 Chemnitz, Germany

Author notes

[* ]Corresponding author. Department of Radiotherapy, University of Rostock, Südring 75, 18059 Rostock, Germany. Tel: +49-381-494-9001; Fax: +49-381-494-9002; Email: marcella.szuecs@ 123456uni-rostock.de

Article

Publisher ID: rru093

DOI: 10.1093/jrr/rru093

PMC ID: 4572584

PubMed ID: 25348250

SO-VID: d4882fb0-b9a0-42d5-90c9-e60d793ca7d6

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 7 June 2014

Date revision received : 6 September 2014

Date accepted : 10 September 2014

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Subjective voice quality, communicative ability and swallowing after definitive radio(chemo)therapy, laryngectomy plus radio(chemo)therapy, or organ conservation surgery plus radio(chemo)therapy for laryngeal and hypopharyngeal cancer

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Most cited references 31

Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group.

Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer.

Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?

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