Purpose

Brachytherapy plays a major role in the treatment of patients with carcinoma of the cervix. However, routine intracavitary brachytherapy may not be feasible or adequate to treat locally advanced disease. The purpose of this retrospective study (spanning a 20-year period) was to determine the outcome of interstitial low-dose-rate brachytherapy in the treatment of bulky or locally advanced cervical cancer. The long-term survival and safety of this technique were evaluated, along with its impact on local and locoregional control, disease-free survival, and complications.

Methods and materials

A total of 185 previously untreated patients with cervical cancer were treated between 1977 and 1997. According to the International Federation of Gynecology and Obstetrics classification, 21 patients had Stage IB (barrel), 77 Stage II, 77 Stage III, and 10 Stage IV disease. All patients were treated by a combination of external megavoltage irradiation to the pelvis to a dose of 5040 cGy followed by interstitial-intracavitary implants to a dose of 40-50 Gy to the implanted volume in two applications.

Results

Clinical local control was achieved in 152 (82%) of the 185 patients. A 5-year disease-free survival rate of 65%, 67%, 49%, and 17% was achieved for patients with Stage IB, II, III, and IV disease, respectively. Eighteen (10%) of the 185 patients developed Radiation Therapy Oncology Group Grade 3 or 4 late complications.

Conclusion

Patients with locally advanced cervical cancer, or with distorted anatomy, may be treated adequately with interstitial brachytherapy to achieve excellent locoregional control and a reasonable chance of cure with acceptable morbidity.

We identify amino acid variants within dominant SARS-CoV-2 T cell epitopes by interrogating global sequence data. Several variants within nucleocapsid and ORF3a epitopes have arisen independently in multiple lineages and result in loss of recognition by epitope-specific T cells assessed by IFN-γ and cytotoxic killing assays. Complete loss of T cell responsiveness was seen due to Q213K in the A∗01:01-restricted CD8+ ORF3a epitope FTSDYYQLY_207-215; due to P13L, P13S, and P13T in the B∗27:05-restricted CD8+ nucleocapsid epitope QRNAPRITF_9-17; and due to T362I and P365S in the A∗03:01/A∗11:01-restricted CD8+ nucleocapsid epitope KTFPPTEPK_361-369. CD8+ T cell lines unable to recognize variant epitopes have diverse T cell receptor repertoires. These data demonstrate the potential for T cell evasion and highlight the need for ongoing surveillance for variants capable of escaping T cell as well as humoral immunity.