125I seed implantation brachytherapy for glottic carcinoma: an experimental and clinical study

Abstract

¹²⁵I seed implantation brachytherapy (ISIB) is the preferred treatment for prostate cancer. Is ISIB technically suitable for glottic carcinoma (GC)? This question has not been answered in the literature; thus, the present study was carried out to evaluate the feasibility and effect of ISIB on GC in animal and clinical studies. An animal model of Tu-212 cell laryngeal carcinoma xenografts (n = 20 animals) underwent ISIB treatments [experimental group (EG) using 0.8-mCi/seed, control group (CG) using 0-mCi/seed]; at 4 weeks, haematoxylin-eosin (HE) staining was performed, and the mRNA and protein expression of Bax, Bcl-2 and PCNA was analysed. Moreover, thirty healthy beagle dogs underwent ISIB under CT guidance (EG, 0.8 mCi/seed, CG, 0 mCi/seed), and injuries to the normal tissue were analysed by HE and Masson staining at 2, 4, and 8 weeks. Finally, twenty-one GC patients (T2-3N0M0) underwent percutaneous ISIB at a mean prescription dose of 116.8 Gy; the technical success, complications, local tumour response, voice quality, local progression and overall survival were analysed. The results showed that the xenograft tumours were significantly inhibited in the EG. The Bax protein levels were significantly increased in this group (P<0.05), while the Bcl-2 and PCNA protein levels were decreased (P<0.05). Moreover, the glottic injury scores increased with the dose accumulation (P<0.05), while the adjacent tissue did not show pathohistological injury, and the routine blood tests showed no change between the pre-treatment baseline levels and the levels 2, 4, or 8 weeks later (P>0.05). The clinical study found that the rate of technical success was 100% with no procedure-related complications; furthermore, complete response was achieved in all patients, and no local progression occurred. All patients survived and showed improvements in their voice quality (P<0.05) during the follow-up period (median 23.5 months). The results show that ISIB is a safe and effective treatment for GC; randomized controlled trials are needed to further evaluate its clinical efficacy.

Keywords: 125I brachytherapy; clinical study; experimental study; glottic carcinoma.

Figure 4

A: Local disinfection and puncture of a normal vocal cord in a beagle dog; B, C: Four ¹²⁵I seeds were implanted on one side of the normal vocal cord under CT guidance; D-F: TPS dose verification and dose volume histogram after ISIB; E: Local radiation damage resulted in mucosal atrophy on the side of the ¹²⁵I seed, while the contralateral side was normal.

Figure 1

A: Tumours in the 0.8-mCi and 0-mCi groups 30 days after ISIB; B: ¹²⁵I seed in the tumour (arrow); C, D: ¹²⁵I seed dose TPS and dose volume histogram, with an absorbed dose of 23.06 Gy at 4 weeks; E: HE showing local necrosis (marked with a star) near the ¹²⁵I seed after 4 weeks of ISIB (×200, bar = 50 μm); F: Tumour weight comparison between the 0.8- and 0-mCi groups; G: Tumour volume comparison between the 0.8- and 0-mCi groups; *P<0.05, **P<0.01.

Figure 2

A, B: mRNA and protein expression of Bax, Bcl-2 and PCNA in the 0.8- and 0-mCi groups, all of which showed significant differences between the groups; *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Figure 3

Protein expression of Bax, Bcl-2 and PCNA in the 0.8- and 0-mCi groups, all of which showed significant differences between the EG and CG (×200, bar = 50 μm); *P<0.05, **P<0.01, ***P<0.001, ****P<0.0001.

Figure 7

A, B: C-arm CT guided ¹²⁵I seed implantation, C, D: Implantation of 10 ¹²⁵I seeds under fluoroscopy; E: The positioning of the ¹²⁵I seeds was confirmed by CT; F: SPECT showing the local nuclide concentration with good dose coverage; G, H: TPS dose verification and dose volume histogram.

Figure 5

HE and Masson staining of vocal cords at different times in the high-activity group. Large white arrow: a small amount of inflammatory cell infiltration; large black arrow: epithelial cell rupture and shedding; small black arrow: epithelial cell proliferation and protrusion; black five-point star: collagen fibre hyperplasia; white five-point star: muscle fibre hyperplasia. HE and Masson staining showing that the radiation injury and fibrosis were gradually aggravated (×100, bar = 100 μm).

Figure 6

Cartilage, thyroid gland and muscle showing a normal structure with no irradiation injury at 8 weeks (×200, bar = 50 μm).

Figure 8

(A-F) An 82-year-old male patient with hoarseness and dyspnoea. (A) Preoperative PET showing that the local metabolism of the right vocal cord was active and involved the anterior commissure; (B) Preoperative laryngoscopy; (C, D, F) Laryngoscopy at 2 months (C), 6 months (D) and 12 months (E) postoperatively showing that the local tumour completely disappeared after ISIB. (F) PET/CT showing no local metabolism 32 months after the operation. (G-I) A 69-year-old male patient with severe hoarseness. (G) Preoperative PET showing active local metabolism in the right vocal cord; (H) A GC was located on the right vocal cord; 24 months after ISIB, the tumour curvature was no longer visible on laryngoscopy.