Purpose: Performing lingual tonsillectomies with transoral robotic surgery (TORS) or laser microsurgery (TLM) may improve the identification rate of hidden primary base-of-tongue (BOT) cancers presenting as squamous cell carcinoma (SCC) of unknown primary (CUP). We evaluated the potential therapeutic value for this approach by comparing differences in radiotherapy (RT) volumes and clinical outcomes for CUP and small BOT carcinomas.
Methods:Retrospective review of BOT (T1N1-3M0) and CUP (T0N1-3M0) patients treated at Princess Margaret Cancer Centre between 2001-2013 with known p16 status. The characteristics of mucosal (CTV-T) and nodal (CTV-N) clinical target volumes, and organ-at-risk (OAR) dosimetry were obtained. Local (LC), regional (RC), distant control (DC), cause-specific (CSS), overall survival (OS) and RTOG grade ≥3 late toxicity (LT) were analyzed.
Results: Fifty-four BOT (93% p16-positive) and 61 CUP (62% p16-positive) patients were identified. Respective N classifications included: N1 (15 vs 8%), N2a (17 vs 31%), N2b (28 vs 36%), N2c (24 vs 8%) and N3 (17 vs 16%). High-dose CTV-T was prescribed in 100% of BOT and 38% of CUP patients (P<0.001). Low-dose CTV-T included mucosal sites outside of the oropharynx (i.e., nasopharynx, hypopharynx, and/or larynx) in 0% of BOT and 26% of CUP patients (P<0.001), with greater volume of low-dose CTV-T in CUP than BOT patients (113+/-8 vs 84+/-6 cm3, P=0.003). Bilateral neck irradiation was used in 53/54 (98%) BOT and 46/61 (75%) CUP patients (P<0.001). OAR dosimetry demonstrated that BOT patients received higher maximum dose (Dmax) to the mandible with a trend toward higher Dmax and lower average dose (Dmean) to the larynx. There were no differences in LC, RC, DC, CSS, and OS between BOT and CUP groups stratified by p16 status (P>0.05). Grade 3 LT recorded in 2 (3%) CUP patients (neck fibrosis) and 5 (9%) BOT patients (2 neck fibrosis, 2 osteoradionecrosis, and 1 dysphagia).
Conclusion: Patients treated with primary RT for CUP or small BOT SCC had similar clinical outcomes. Identifying small volume hidden BOT primary carcinomas using TORS or TLM suggests a reduction in the volume of low-dose CTV-T, with more frequent use of high-dose CTV-T and bilateral neck irradiation. Future studies are required to investigate the potential impact of these volumetric and dosimetric differences on quality-of-life and functional outcomes.
Clinical outcomes for BOT and CUP carcinomas
| |
p16-postive BOT
n=50 |
p16-positive CUP
n=38 |
P-value |
p16-negative BOT
n=4 |
p16-negative CUP
n=23 |
P-value |
| Median (range) follow up (years) |
5.2
(0.2-10) |
3.3
(0.6-8.4) |
|
8.3
(7.2-9.4) |
1.9
(0.2-5.6) |
|
| 3-year LC |
100% |
95% |
0.19 |
75% |
100% |
0.57 |
| 3-year RC |
98% |
100% |
0.68 |
75% |
82% |
0.87 |
| 3-year DC |
94% |
91% |
0.67 |
100% |
85% |
0.44 |
| 3-year CSS |
94% |
93% |
0.55 |
75% |
85% |
0.6 |
| 3-year OS |
88% |
91% |
0.78 |
50% |
74% |
0.59 |
OAR dosimetry for BOT and CUP carcinomas
| |
BOT
n=54 |
CUP
n=61 |
P-value |
| Dmax, mandible |
71+/-4.5 |
67.2+/- 6.7 |
0.001 |
| Dmean, mandible |
42.8+/-5 |
41+/-8.1 |
0.188 |
| Dmax, larynx |
66.1+/-7.6 |
62.8+/-9.3 |
0.059 |
| Dmean, larynx |
43.8+/-7.5 |
47.1+/-10.7 |
0.071 |
| Dmax, inferior constrictor |
63.5+/-6.9 |
62.1+/-7.8 |
0.35 |
| Dmean, inferior constrictor |
43.7+/-6.4 |
45.2+/-10.4 |
0.37 |
| Dmax, esophagus |
54.7+/-7.8 |
54.4+/-9.5 |
0.83 |
| Dmean, esophagus |
32.5+/-9.3 |
30.2+/-10.4 |
0.26 |