Clinical outcomes in patients with adamantinoma: Report from the bone and soft tissue tumor registry in Japan

Adamantinomas are rare malignant bone tumors. Due to their low incidence, there are few reports on the clinical results of adamantinoma.

propensity for distant metastasis and local recurrence. 7After incomplete resection, however, the recurrence rate has been reported to be up to 30%. 8Metastatic adamantinoma has a reportedly poor prognosis. 9Because of its rarity, there is a paucity of information on survival rates and treatment options.
In Japan, the National Bone and Soft Tissue Tumor (BSTT) Registry has been used to analyze treatment outcomes for rare bone tumors.The purpose of this study was to clarify the clinical profile of adamantinomas in Japan using data from the BSTT registry.

| MATERIALS AND METHODS
The BSTT registry is a nationwide organ-specific cancer registry for BSTTs in Japan. 10The registry is organized and funded by the Japanese Orthopaedic Association (JOA) and promoted by the National Cancer Twenty-four were male and 14 were female, with a mean age of 37 (6-87) years and a mean follow-up of 35 (1-128) months (Table 1).This study included pathological diagnosis, site of origin, tumor diameter, skip metastasis, compartment, lymph node and distant metastasis, histological grade, and Enneking stage. 11We performed analysis on biopsy type, treatment method, surgical margin, reconstruction type, surgical technique, and method of reconstruction.The Kaplan-Meier survival method was used to estimate survival.

| RESULTS
The site of origin was the proximal tibia in 4 cases, diaphysis in 32 cases, distal tibia in one case, and unknown in one case.The mean tumor size was 11 cm.Histological grade was reported as low in T A B L E 1 Demographic and clinical characteristics of patients.3).
Reconstruction using FVFG was performed in three out of six cases (50%) with nonunion of grafting bone.Oncologic outcomes were death from other causes (DOC) in only one case and no evidence of disease (NED) in 37 cases (Table 4).The overall 5-year survival rate was 91.7% (Figures 1-4).

| DISCUSSION
In this study, we evaluated the oncological outcomes of tibia adamantinoma using the Japanese National BSTT Registry.In our series of 38 patients with tibia adamantinoma, outcome status was NED for 37 patients (97%) and DOC for one patient, after a mean follow-up of 35 months.
Adamantinomas are low-grade bone tumors that occur in the long bones, with a predilection for the tibia. 1,12,13Males are at slightly higher risk than females. 1,12,14,15They are most common between the ages of 20 and 50 years, and childhood onset is rare. 7,15,16The most common site of origin is the diaphyses of the long bones, and 80%-85% of cases occur in the tibia. 9Conversely, the ribs, fingers, and spine are rarely involved.Initial symptoms are reported as swelling and pain, and in 30% of cases, symptoms may persist for several years or more.Pulmonary and lymph node metastases may also be present.Imaging findings are osteolytic, and sclerotic lesions may be seen in the periphery.A "soap-bubble sign" is often present.It is important to distinguish adamantinoma from fibrous dysplasia and osteofibrous dysplasia on imaging, but this is often challenging.
Magnetic resonance imaging shows low signal on T1-weighted images and high signal on T2-weighted images. 9amantinomas are slowly progressing malignant bone tumors.
In recent years, en bloc resection has often been the treatment of choice, but because of the rarity of this tumor, there are no clear treatment guidelines.There is no evidence of the effectiveness of radiation therapy or chemotherapy as treatment for adamantinomas.
Intralesional and marginal resection reportedly increase the risk of recurrence.
Mortality associated with adamantinomas is reported to be 12%-17% 1 ; the 5-year survival rate is reportedly 92%-98.8%. 14,17her reports on the clinical outcomes of adamantinomas are summarized in Table 5.Overall, we found favorable outcomes, with 37 of the 38 patients (97%) showing NED at final follow-up.However, 11 patients (29%) required revision surgery.The most common reason for revision was bone fusion failure related to reconstruction.Houdek et al.
analyzed 46 cases of adamantinomas and reported that 39% of the patients later required reoperation. 15In the present study, the major complications were delayed or nonunion at host reconstruction sites.
Compared to previous studies, the rate of revision surgery was slightly lower.In Japan, the main reconstruction methods are FVFG and EDA.
FVFG is technically more difficult and requires longer operative time but is considered to have lower risks of nonunion and fracture.
In contrast, VFG and allografts are more commonly used for reconstruction in other countries.
The strong point of this study is that it is the first Asian study of adamantinomas to use a multicenter registry.We have two limitations in this study.First is the short follow-up period.
Schwarzkopf et al. 18 reported that local recurrence and distant metastasis occurred after more than 20 years from initial diagnosis.
Especially in low-grade malignant tumors, longer follow-up periods may be necessary.However, because Japan's National BSTT Registry began gathering data in 2006, it is not yet possible to perform studies with longer follow-up periods.Clinicians should keep in mind the potential for adamantinomas to recur and metastasize even 20 or more years after resection.Second, because this study is based on a national registry, some patient data is unavailable, such as pathological diagnoses and details of surgical procedures.

| CONCLUSIONS
We evaluated the oncological outcomes of tibia adamantinoma using the Japanese BSTT Registry.The results of treatment of adamantinomas in Japan have been extremely favorable.
Center.Detailed data for patients treated at participating hospitals are collected annually in a two-part survey completed by physicians.The first part collects patient characteristics including basic patient data (sex, age, date of diagnosis, and treatment status at first visit [initial therapy: yes or no]), tumor data (diagnosis, histological details [malignant or benign disease and histological grade for malignant tumors], tumor location, and data required for TNM staging [Seventh Edition AJCC staging]), surgical data (date of definitive surgery, type of surgery, and additional surgery for complications) and information about neoadjuvant/adjuvant treatment (including chemotherapy, radiotherapy, and/or hyperthermia).The second part of the survey collects information on prognosis at 2, 5, and 10 years after the initial registration.This includes information about several outcomes at the time of the latest followup, such as local recurrence, distant metastasis, and oncological outcome.The use of the BSTT database for clinical research was initiated in 2014 following approval by the Musculoskeletal Tumor Committee of the JOA.This study received Institutional Review Board approval.Of the adamantinoma cases registered in the National BSTT Registry from 2006 to 2019, 38 cases of tibial origin were included.

F I G U R E 1
The Kaplan-Meier curve shows the proportion of surviving patients plotted against the months from diagnosis to death or final follow-up.The overall 5-year survival rate was 91.7%.F I G U R E 2 Preoperative radiograph showing adamantinoma in the tibia of a 7-year-old boy.An eccentric osteolytic multilocular lesion with well-circumscribed sclerotic margin is visible (A: anteroposterior view, B: mediolateral view).F I G U R E 3 T1-weighted gadolinium-enhanced fat-suppressed MRI showing the tumor depicted as a highly enhanced lesion.MRI, magnetic resonance imaging.
Treatment of patients with adamantinoma.
T A B L E 3 Complications in patients with adamantinoma.