The feasibility of reducing fractions in early-stage laryngeal cancer has not previously been prospectively studied, and we will therefore conduct a careful phase I bio-equivalent dose fraction reduction study.

Patients enrolled at each dose level will undergo routine evaluations to identify potential toxicities as well functional voice analyses. Adequate waiting periods will be used to ensure that fraction reduction does not proceed prior to observing toxicity. The purpose of the study will be either to determine the maximal fraction reduction possible until a dose is reached where a dose-limiting toxicity occurs. The initial dose and fractionation will be 50 Gy in 15 fractions with the goal to reduce number of fractions to a dose of 42.5 Gy in 5 fractions. The rationale for using 5 fractions is that it is tolerated in centrally located lung tumors at a dose of 50 Gy in 5 fractions, and thus, is likely to be tolerated in large calliber airways.

Inclusion Criteria:

3.1.1 Stage Tis, T1, or T2 laryngeal squamous cancer as defined by American Joint Commission on Cancer (AJCC) 2007 staging system

3.1.2 Biopsy proven squamous cell carcinoma histology or squamous cell variants (sarcomatoid, verrucous, basaloid, and papillary subtypes) involving the true vocal cord

3.1.3 Direct laryngoscopy showing no evidence of greater than Stage II true glottic larynx cancer

3.1.4 PET/CT, X-ray, CT-scan of the chest showing no evidence of metastatic disease

3.1.5 PET/CT or CT-scan of the neck showing no evidence of nodal involvement

3.1.6 Age ≥ 18 years.

3.1.7 Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

3.1.7.1 A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:

• Has not undergone a hysterectomy or bilateral oophorectomy; or
• Has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).

3.1.8 Ability to understand and the willingness to sign a written informed consent

3.1.9 Eastern Cooperative Oncology Group (ECOG) performance status 0-1

3.1.10 Negative Urine β-HCG or negative serum quantitative β-HCG or within 2 weeks prior to registration for women of childbearing potential

Exclusion Criteria:

3.2.1 Evidence of fixed vocal cord (Stage cT3)

3.2.2 Evidence of thyroid or soft tissue invasion (Stage cT4)

3.2.3 Evidence of positive nodal disease (Stage N1)

3.2.4 Evidence of metastatic disease (Stage M1)

3.2.5 Subjects may not be receiving any other investigational agents.

3.2.6 Non-squamous histology including lymphoma, neuroendocrine carcinoma, adenocarcinoma, or other histology.

3.2.7 Previous laryngeal surgery.

3.2.8 Previous laser therapy within one year prior to protocol treatment.

3.2.9 Previous head and neck radiation therapy involving the glottic larynx

3.2.10 Patients with collagen vascular disease, specifically dermatomyositis with a CPK level above normal or active skin rash, systemic lupus erythematosis, or scleroderma.

3.2.11 Any prior treatment with radiation therapy or chemotherapy for the currently diagnosed larynx cancer prior to registration.

3.2.12 History of another active uncontrolled malignancy at the time of study enrollment

3.2.13 Subjects must not be pregnant due to the potential for congenital abnormalities.

3.2.14 Patients smoking in excess of 2 packs of cigarettes per day.

3.2.15 ECOG performance status ≥ 2

3.2.16 Life expectancy < 3 years