Treatment Option Overview
Small superficial cancers without laryngeal fixation or lymph node involvement are successfully treated by radiation therapy or surgery alone, including laser excision surgery. Radiation therapy may be selected to preserve the voice and to reserve surgery for salvaging failures. The radiation field and dose are determined by the location and size of the primary tumor. A variety of curative surgical procedures are also recommended for laryngeal cancers, some of which preserve vocal function. An appropriate surgical procedure must be considered for each patient, given the anatomic problem, performance status, and clinical expertise of the treatment team. Advanced laryngeal cancers are often treated by combining radiation with concurrent chemotherapy for larynx preservation and total laryngectomy for bulky T4 disease or salvage.[1-6]
Evaluation of treatment outcome can be reported in various ways: locoregional control, disease-free survival, determinate survival, and overall survival (OS) at 2 to 5 years. Preservation of voice is an important parameter to evaluate. Outcome should be reported after initial surgery, initial radiation, planned combined treatment, or surgical salvage of radiation failures. Primary source material should be consulted to review these differences.
A review of published clinical results of radical radiation therapy for head and neck cancer suggests a significant loss of local control when the administration of radiation therapy was prolonged; therefore, lengthening of standard treatment schedules should be avoided whenever possible.[7,8]
Direct comparison of the results of radiation therapy versus endolaryngeal surgery (with or without laser) has not been made for patients with early stage laryngeal cancer. The evidence is insufficient to show a clear difference in the results between treatment options in regard to local control or OS. Retrospective data suggests that in comparison with surgery, radiation therapy might cause less perturbation of voice quality without a significant difference in patient perception.
A direct comparison of chemotherapy followed by radiation therapy versus upfront surgery was made by The Department of Veterans Affairs (VA) Laryngeal Cancer Study Group in a trial in which 332 patients were randomly assigned to three cycles of chemotherapy (cisplatin and fluorouracil) and radiation therapy or surgery and radiation therapy. After two cycles of chemotherapy, the clinical tumor response was complete in 31% of the patients, and there was a partial response in 54% of the patients. Survival was similar in both arms; however, larynx preservation was possible in 64% of the patients in the chemotherapy-followed-by-radiation therapy arm.
The VA study was followed up in a randomized study, RTOG-91-11 (NCT00002496), in which the laryngeal preservation arm of the VA study was compared with the concomitant chemoradiation and radiation-alone arms, and the primary endpoint was laryngectomy-free survival (LFS). The RTOG 91-11 study evaluated 547 patients with locally advanced laryngeal cancer who were enrolled between August 1992 and May 2000, with a median follow-up for surviving patients of 10.8 years (range, 0.07–17 years). Three regimens were compared, including induction chemotherapy plus radiation therapy, concomitant chemoradiation, and radiation therapy alone. Both chemotherapy regimens improved LFS compared with radiation therapy alone (induction chemotherapy vs. radiation therapy alone, hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.59–0.95; P = .02; concomitant chemotherapy vs. radiation therapy alone, HR, 0.78; 95% CI, 0.78–0.98; P = .03).
Concurrent radiation therapy plus cisplatin resulted in a statistically significantly higher percentage of patients with an intact larynx at 10 years (67.5% for patients who had induction chemotherapy; 81.7% for patients who had concomitant chemotherapy; and 63.8% for patients who received radiation alone); 80% of laryngectomies were performed during the first 2 years (84 laryngectomies during year 1 and 35 laryngectomies during year 2).
Concomitant cisplatin with radiation therapy resulted in a 41% reduction in risk of locoregional failure compared with radiation therapy alone (HR, 0.59; 95% CI, 0.43–0.82; P = .0015) and a 34% reduction in risk compared with induction chemotherapy (HR, 0.66; 95% CI, 0.48–0.92; P = .004). Both chemotherapy regimens had a lower incidence of distant metastases, although this did not reach statistical significance compared with radiation therapy alone.
The 10-year cumulative rates of late toxicity (grades 3–5) were 30.6% for induction chemotherapy, 33.3% for concomitant chemotherapy, and 38% for radiation alone, and were not significantly different between the arms.
OS was not significantly different between the groups, although there was possibly a worse outcome in the concomitant groups compared with the induction chemotherapy group (HR, 1.25; 95% CI, 0.98–1.61; P = .08). The OS rates were 58% (5 year) and 39% (10 year) for induction chemotherapy, 55% (5 year) and 28% (10 year) for concomitant chemoradiation, and 54% (5 year) and 32% (10 year) for radiation alone. The number of deaths not attributed to larynx cancer or treatment were higher with concomitant chemotherapy (30.8% vs. 20.8% with induction chemotherapy and 16.9% with radiation alone), because after approximately 4.5 years, the survival curves began to separate and favor induction, although the difference was not statistically significant.
The risk of lymph node metastases in patients with stage I glottic cancer ranges from 0% to 2%, and for more advanced disease, such as stage II and stage III glottic, the incidence is only 10% and 15%, respectively. Thus, there is no need to treat glottic cancer cervical lymph nodes electively in patients with stage I tumors and small stage II tumors. Consideration should be given to using elective neck radiation for larger or supraglottic tumors.
For patients with cancer of the subglottis, combined modality therapy is generally preferred for the uncommon small lesions (i.e., stage I or stage II); however, radiation therapy alone may be used.
Patients who smoke during radiation therapy appear to have lower response rates and shorter survival durations than those who do not; therefore, patients should be counseled to stop smoking before beginning radiation therapy.
Accumulating evidence has demonstrated a high incidence (i.e., >30%–40%) of hypothyroidism in patients who have received external-beam radiation to the entire thyroid gland or to the pituitary gland. Thyroid-junction testing of patients should be considered prior to therapy and as part of posttreatment follow-up.[13,14]
- Silver CE, Ferlito A: Surgery for Cancer of the Larynx and Related Structures. 2nd ed. Philadelphia, Pa: Saunders, 1996.
- Wang CC, ed.: Radiation Therapy for Head and Neck Neoplasms. 3rd ed. New York: Wiley-Liss, 1997.
- Thawley SE, Panje WR, Batsakis JG, et al., eds.: Comprehensive Management of Head and Neck Tumors. 2nd ed. Philadelphia, Pa: WB Saunders, 1999.
- Mendenhall WM, Werning JW, Pfister DG: Treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 729-80.
- Chepeha DR, Haxer MJ, Lyden T: Rehabilitation after treatment of head and neck cancer. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 781-8.
- Forastiere AA, Zhang Q, Weber RS, et al.: 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. J Clin Oncol 31 (7): 845-52, 2013. [PUBMED Abstract]
- Fowler JF, Lindstrom MJ: Loss of local control with prolongation in radiotherapy. Int J Radiat Oncol Biol Phys 23 (2): 457-67, 1992. [PUBMED Abstract]
- Hansen O, Overgaard J, Hansen HS, et al.: Importance of overall treatment time for the outcome of radiotherapy of advanced head and neck carcinoma: dependency on tumor differentiation. Radiother Oncol 43 (1): 47-51, 1997. [PUBMED Abstract]
- Yoo J, Lacchetti C, Hammond JA, et al.: Role of endolaryngeal surgery (with or without laser) compared with radiotherapy in the management of early (T1) glottic cancer: a clinical practice guideline. Curr Oncol 20 (2): e132-5, 2013. [PUBMED Abstract]
- Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. The Department of Veterans Affairs Laryngeal Cancer Study Group. N Engl J Med 324 (24): 1685-90, 1991. [PUBMED Abstract]
- Spaulding CA, Hahn SS, Constable WC: The effectiveness of treatment of lymph nodes in cancers of the pyriform sinus and supraglottis. Int J Radiat Oncol Biol Phys 13 (7): 963-8, 1987. [PUBMED Abstract]
- Browman GP, Wong G, Hodson I, et al.: Influence of cigarette smoking on the efficacy of radiation therapy in head and neck cancer. N Engl J Med 328 (3): 159-63, 1993. [PUBMED Abstract]
- Turner SL, Tiver KW, Boyages SC: Thyroid dysfunction following radiotherapy for head and neck cancer. Int J Radiat Oncol Biol Phys 31 (2): 279-83, 1995. [PUBMED Abstract]
- Constine LS: What else don't we know about the late effects of radiation in patients treated for head and neck cancer? Int J Radiat Oncol Biol Phys 31 (2): 427-9, 1995. [PUBMED Abstract]