Radiation Oncology/Head & Neck/Larynx/Supraglottis

Anatomy

• Subsites of the supraglottic larynx: epiglottis, arytenoid cartilages, false cords, aryepiglottic folds
• Major lymphatic drainage of supraglottic larynx are levels II, III, IV.
• 55% clinically positive nodes at diagnosis, 16% bilateral
• Anatomic Landmarks
  • Hyoid bone - C3
  • Superior border of thyroid cartilage - C4
  • Cricoid cartilage - C6

Staging

AJCC Staging System

• Tumor
  • T1 - limited to one subsite, normal vocal cord mobility
  • T2 - more than one adjacent subsite, but no fixation of vocal cords
  • T3 - vocal cord fixation, or invasion of the following: postcricoid area, pre-epiglottic tissues, paraglottic space, or minor thyroid cartilage erosion (inner cortex)
  • T4a - invades through thyroid cartilage or invades tissues beyond the larynx (trachea, soft tissue of neck, extrinsic muscles of the tongue, strap muscles, thyroid, esophagus)

    Note: extrinsic muscles of the tongue are: genioglossus, hyoglossus, styloglossus, and palatoglossus

  • T4b - invades prevertebral space, carotid, or mediastinum

• Nodes (same as for most H&N sites)

NX - Cannot be assessed N0 - No regional lymph nodes metastasis N1 - Single ipsilateral lymph node, <= 3cm in greatest dimension N2 N2a - Single ipsilateral lymph node, 3-6 cm in greatest dimension N2b - Multiple ipsilateral lymph nodes, <= 6cm in greatest dimension N2c - Bilateral or contralateral lymph nodes, <= 6cm in greatest dimension N3 - Lymph node(s) >6 cm in greatest dimension

• Metastasis
  • M0 - none
  • M1 - yes

Stage Grouping

• Stage I - T1N0
• Stage II - T2N0
• Stage III - T3N0, T1-3N1
• Stage IVA - T4a or N2
• Stage IVB - T4b or N3
• Stage IVC - M1

Treatment

• T1 and favorable T2N0 can be treated w/ definitive xrt or larynx conserving surgery.
• Unfavorable T2N0 can be treated w/ definitive chemoxrt or larynx conserving surgery.
• Indications for postoperative xrt include: close/positive margins, LVI, PNI
• Locally advanced disease should be treated with definitive chemoxrt

Pre-op RT vs. Post-op RT

• RTOG 73-03 (1973-1979)
  • Randomized. 320 patients. Operable stage T2-T4 any N (but not fixed); oral cavity, oropharynx, supraglottic larynx, hypopharynx, or maxillary sinus. Arm 1) Pre-op RT 50 Gy vs. Arm 2) Post-op RT 60 Gy. In addition, OC and OP lesions may be randomized Arm 3) definitive RT 65-70 Gy, with surgery reserved for salvage (n=43).
  • 10-years; 1999 PMID 1993628 — "Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03." (Tupchong L et al. Int J Radiat Oncol Biol Phys. 1991 Jan;20(1):21-8.)
    • Only pre-op vs. post-op subset (n=277). Oral cavity (14%), oropharynx (17%), hypopharynx (43%), supraglottic larynx (26%)
    • Outcome: LRC pre-op 58% vs. post-op 70% (SS), <2 years no difference (failures 59% vs. 58%), but marked >2 years (failures 27% vs 8%); OS no difference due to late (>2 years) deaths from DM and from second primaries
    • Supraglottic larynx: LRC pre-op 53% vs. post-op 77% (SS); 78% failures <2 years
    • Toxicity: no difference
    • Conclusion: Post-op RT better for LRC (especially in SGL), but no impact on OS due to distant failure and second primaries
  • Comment: some argument for definitive chemoRT instead of surgery and post-op RT since after 2 yrs, distant mets are primary cause of failure resulting in similar 10 OS in this trial. LRC still better for post-op vs definitive RT alone. Also, different doses used, at the time believed equivalent given the setting

Definitive RT

• Varese, Italy, 1997 (1983-92) PMID 9282245 -- Spriano G et al. "Conservative management of T1-T2N0 supraglottic cancer: a retrospective study." Am J Otolaryngol. 1997 Sep-Oct;18(5):299-305.
  • 166 pts w/ SGL CA tx'd w/ larynx conserving surgery or definitive xrt
  • DFS 88% (surg) vs 76% (xrt)
  • Ultimate local control for xrt was 92% if salvage surgery was taken into account.
  • Likely of salvage rescuing a local failure was ~50%.
  • Larynx preservation rate was 95% (surg) vs 72% (xrt)

• Rotterdam, 1990 (1965-79) PMID 2298616 -- Hoekstra CJ et al. "Squamous cell carcinoma of the supraglottic larynx without clinically detectable lymph node metastases: problem of local relapse and influence of overall treatment time." Int J Radiat Oncol Biol Phys. 1990 Jan;18(1):13-21.
  • 203 pts w/ SCC of SGL tx'd curatively. 193 tx'd w/ primary xrt reserving surgery for salvage; re-evaluation occurred at 40 Gy and definitive course to 60-70 Gy was given if pts had response at re-eval. 33 pts required surgery.
  • 53% RFS for T2, 39% RFS for T4

Hyperfractionation

• MDACC, 1989 (1984-87) PMID 2808039 -- Wendt CD et al. "Hyperfractionated radiotherapy in the treatment of squamous cell carcinomas of the supraglottic larynx." Int J Radiat Oncol Biol Phys. 1989 Nov;17(5):1057-62.
  • 41 pts w/ SCC of SGL tx'd w/ 1.2 Gy BID to 72-79 Gy (76.8 median).
  • Local control rates improved w/ hyperfractionation over historical MDACC controls (96% vs 82% at 1 yr, 87% vs 76% at 2 yrs).

• MGH, 1986 (1979-84) PMID 3943989 -- Wang CC et al. "Twice-a-day radiation therapy for supraglottic carcinoma." Int J Radiat Oncol Biol Phys. 1986 Jan;12(1):3-7.
  • 106 pts tx'd w/ 1.6 Gy BID to 64 Gy in split course compared to 79 pts tx'd w/ conventional fractionation to 65 Gy
  • 3yr local control was 76% (hyperfractionated) vs 50% (conventional)
  • 3yr local control for T1/T2 was 88% vs 63%
  • 3yr local control for T3/T4 was 66% vs 33%

Induction Chemo-RT vs. Primary RT alone

• RTOG 68-01 -- methotrexate
  • Randomized. 638 patients, Stage III-IV oral cavity (23%), oropharynx (55%), supraglottic larynx (12%), hypopharynx (10%). Arm 1) RT alone vs. Arm 2) IV MTX 25 mg q3d x5 followed by RT. RT 55-80 Gy
  • 1980 PMID 7410127 -- "Adjuvant intravenous methotrexate or definitive radiotherapy alone for advanced squamous cancers of the oral cavity, oropharynx, supraglottic larynx or hypopharynx." (Fazekas JT, Int J Radiat Oncol Biol Phys. 1980 May;6(5):533-41.)
    • Outcome: median OS RT vs. MTX-RT: oral cavity 11.8 mo vs. 12.4 mo, oropharynx 13.6 mo vs. 13.1 mo, SGL 17.2 mo vs. 19.2 mo, hypopharynx 9.7 mo vs. 13.4 mo
    • Conclusion: Minimal gain, induction methotrexate should not be used

Salvage Surgery

• Gainesville, 1995 (1964-91) PMID 7790245 -- Parsons JT et al. "Salvage surgery following radiation failure in squamous cell carcinoma of the supraglottic larynx." Int J Radiat Oncol Biol Phys. 1995 Jun 15;32(3):605-9.
  • 206 pts tx'd curatively w/ xrt. 46 pts had local failure (22%). Deemed successful surgical salvage if NED at 2 yrs.
  • 26 pts had total laryngectomy, 4 had voice sparing salvage procedure.
  • Most failures after salvage were b/c of inability to control local dz.
  • Rate of post-surgical complications 37%
  • 1/2 to 2/3 of pts w/ local failure undergo salvage surgery. 25-30% long term DFS in this population.