Metastatic lymph nodes often need intervention after comprehensive treatment of head, neck and chest tumors. Since the first course of radiotherapy often leads to local tissue fibrosis and vascular occlusion, it is difficult for drugs to pass through, and coupled with the poor physical condition of patients with advanced tumors, it is difficult to tolerate the adverse reactions arising from chemotherapy and other drugs, local treatment becomes an essential part. Temam et al. [2] have suggested that only 20% of patients with recurrence can undergo palliative surgery due to local structural disturbances arising from the initial surgery and external radiation. With the continuous improvement of radiotherapy techniques, high-dose rate brachytherapy has been well employed in a wide variety of solid tumors [3, 4] (e.g., good results in metastatic lymph nodes) [5, 6]. In this study, 38 patients who received 192Ir high-dose-rate brachytherapy for neck metastatic lymph nodes that recurred in the field after radiotherapy were analyzed retrospectively.

The recent efficacy is an important index to assess the treatment effect. The efficacy evaluation results of this study indicated that the overall remission rate (CR + PR) of 52 lymph nodes reached 76.9%, comprising 89.5% (34/38) for lymph nodes less than or equal to 3 cm and 42.9% (6/14) for lymph nodes over 3 cm, P = 0.028. In the previous literature, in Nikolaos Tselis et al [7], 74 patients were treated for inoperable recurrent cervical lymphadenopathy with 192Ir High-Dose-Rate Brachytherapy, with a 67% probability of local control at 1, 2, and 3 years. In Christos Kolotas et al [8], 49 recurrent metastatic neck lesions underwent 192Ir High-Dose-Rate Brachytherapy, with a response rate of 83% (41/49), a complete response of 20% (10/49), a partial response of 63% (31/49), and 8/49 patients (17%) who did not respond to the treatment at a minimum of 6 weeks of follow-up. After a median follow-up of 19 months, the local control rate was 69%, with 15/49 patients (30%) experiencing localized disease progression. Although the overall response rate of this study is similar to the above studies, the follow-up period is still short, and the evaluation of long-term efficacy needs to be further analyzed.

Particle therapy, a minimally invasive treatment modality, has accumulated considerable experience treating neck lymph nodes. In a study by Jiang Yuliang et al. [9], the recent efficacy of 125I particles in 36 patients with recurrent neck lymph nodes after radiotherapy for head and neck tumors was manifested as seven patients of complete remissions, 21 patients of partial remissions, six patients of no changes, and two patients of progressions in the whole group, at an effective rate of 81%. The recent efficacy of this study is similar to it. Both modalities are similar in that they can achieve rapid dose drop in a small area, killing the tumor by high dose radiation and protecting the surrounding endangered organs well. Moreover, tumors are often resistant to radiotherapy in terms of patients previously administrated with radiotherapy. Relevant literature has suggested that the radiation-resistant tumor treatment effect can be increased by increasing the single dose, reducing the number of divisions, and shortening the treatment time. Under the effect of the single large dose of radiation energy in high-dose rate brachytherapy, tumor cells become more susceptible to lethal injury, anti-tumor immunity is induced, T-cell immunity is activated, and a regional or distant metastasis distant tumor suppression effect is formed [10, 11]. On the other hand, the correlation between lymph node size and the efficacy of high-dose rate brachytherapy was analyzed in this study. In the study by Wang Juan [12]et al., 17 patients were administrated with recurrence of metastatic lymph nodes in the neck who had previously received external radiotherapy with particle implantation. The local control rate reached 65.2%, where the control rate of lymph nodes smaller than 4 cm (CR + PR) was determined as 90%, while the control rate of lymph nodes larger than 4 cm was 46%, P = 0.038; the difference achieved statistical significance; the control rate of 21 lymph nodes with isolated and clear borders was obtained as 71%, and the control rate of lymph nodes with fusion and unclear borders reached 0. The control rate of 21 isolated lymph nodes with clear borders determined as 71%, and the local control rate of fused lymph nodes with unclear borders reached 0. In another study, Ashamalla et al. [13] reported a local control rate of 64% for head and neck malignancies < 2.5 cm in diameter and 33% for > 2.5 cm in diameter using radioactive particles. The present study also showed poor control of larger lymph nodes compared to the above two studies. To be specific, 12 patients of CR, 22 patients of PR, 4 patients of SD, and 0 patients of PD in lymph nodes less than or equal to 3 cm, with an objective remission rate of 89.5% (34/38), and 2 patients of CR, 4 patients of PR, 4 patients of SD, and 4 patients of PD in lymph nodes greater than 3 cm, with an objective remission rate of 42.9% (6/14), P = 0.028, which achieved statistical significance, suggesting the effect of high-dose rate brachytherapy can be accurate for ≤ 3 cm lymph nodes. Although no statistical difference was identified between the different subdivisions of the neck and the efficacy in this study, Level II and III of the neck were adjacent to the spinal cord, pharynx, large blood vessels in the neck and other endangered organs, such that the difficulty of needle access was often increased, and it was also limited by the dose. Four patients with unclear relationship with surrounding tissues and enlarged lymph nodes larger than 5 cm were in Level III in this study, two of which was adjacent to the spinal cord and two to the pharynx, and the prescribed dose was 20 Gy/1f in two patients, with an effective peripheral biological dose of 60 Gy and short-term progression after loading at high-dose-rates. There are two reasons for the above-mentioned result. 1. large tumor size. As the tumor size is increased, the blood supply to the center of the tumor becomes poorer, and the percentage of hypoxic cells is increased, resulting in increased radiation resistance. 2. insufficient dose. Fletcher et al. [14] reported that for a 5-cm diameter adenocarcinoma tumor, the external irradiation dose should be 80–90 Gy or even 100 Gy, and the peripheral dose is a direct factor affecting the efficacy. The peripheral dose exerts a direct effect on the efficacy, which may be better if the peripheral dose exceeds 75 Gy. In contrast, the prescribed dose of high-dose rate brachytherapy given to metastatic lymph nodes that progressed after treatment in this study was 20 Gy/1f, with an effective peripheral biological dose of 60 Gy, which is a low dose compared with previous reports in the literature, and the tumor control was poor. Therefore, for larger lymph nodes or lymph nodes with unclear relationship to surrounding tissues, it is unknown whether increasing the brachytherapy dose can improve the local remission rate while ensuring that normal tissues can tolerate it, and further studies are needed.

In terms of adverse reactions, there were four patients of skin injury: grade II, six patients of grade I, and no grade III or IV skin injury; bone marrow suppression: two patients of leukopenia grade I; no serious complications (e.g., hemorrhage, infection, or other organ damage). Grade III-IV complications occurred in 13% of patients in the study by Nikolaos Tselis et al [7]. In the study by Christos Kolotas et al [8], for skin reactions, 13% grade II reactions and 4% grade III reactions were seen. No carotid bursts or hemorrhages were seen in any of the patients. No late complications occurred in any of the patients. The lesser radioskin injury in the present study compared to the present study may be considered to be related to the small size and location of the recurrent lymph nodes in our patients. In contrast, Lee et al. [15]reported that grade 3–4 radiotherapy adverse reactions occurred in 38% of 21 patients with neck lymph node recurrence who underwent re-course radiotherapy. Wang Juan [12] et al. have suggested that acute cutaneous radiotherapy reactions after particle implantation were re-evaluated: eight patients of grade II, 7 patients of grade I, and two patients of grade 0. No significant serious complications (e.g., spinal cord damage, pharyngeal edema, infection, and bleeding) were identified. As indicated by the above result, in terms of adverse reactions, the insertion of post-implantation radiotherapy is not inferior to particle implantation treatment and is significantly better than re-course radiotherapy.

This study also had some limitations: (1) as a retrospective study, the sample size was small and the patients underwent multiple treatment modalities, such that the sample was heterogeneous to a certain extent; (2) to set the prescribed dose, the size and location of the tumors of the patients were considered, and a more flexible individualized treatment plan was adopted, such causing differences in the prescribed dose (single dose of 20–30 Gy). In brief, 192Ir high-dose-rate brachytherapy shows potential advantages as an alternative local treatment for recurrent or residual neck metastatic lymph nodes in the field after external radiotherapy for its recent efficacy (especially for ≤ 3 cm lymph nodes) and low incidence and tolerability of adverse events. In patients with cervical lymphadenopathy who have recurrent head and neck tumors,192Ir high-dose-rate brachytherapy, plays an important role in providing palliative care and tumor control [7, 8]. Still, the small number of patients and short follow-up time should be studied in depth.