Radiation Oncology/Head & Neck/Larynx/Supraglottis

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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 of supraglottis or glottis or regional outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus), 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.

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