Long-term functional outcome of limb-sparing surgery for paediatric bone sarcoma around the knee.

Aims: Surgical limb sparing for knee-bearing paediatric bone sarcoma is considered to have a clinically significant influence on postoperative function due to complications and leg-length discrepancies. However, researchers have not fully evaluated the long-term postoperative functional outcomes. Therefore, in this study, we aimed to elucidate the risk factors and long-term functional prognosis associated with paediatric limb-sparing surgery. Methods: We reviewed 40 patients aged under 14 years who underwent limb-sparing surgery for knee bone sarcoma (15 cases in the proximal tibia and 25 in the distal femur) between January 2000 and December 2013, and were followed up for a minimum of five years. A total of 35 patients underwent reconstruction using artificial materials, and five underwent biological reconstruction. We evaluated the patients' postoperative complications, survival rate of reconstruction material, and limb, limb function, and leg-length discrepancy at the final follow-up, as well as the risk factors for each. Results: Complications were observed in 55% (22/40) of patients. The limb survival and reconstruction material rates at five and ten years were 95% and 91%, and 88% and 66%, respectively. Infection was the only risk factor in both survivals (p < 0.001, p = 0.019). In the 35 patients with limb preservation, the median International Society of Limb Salvage (ISOLS) score at the final follow-up was 80 (47% to 97%). Younger age (p = 0.027) and complications (p = 0.005) were poor prognostic factors. A negative correlation was found between age and leg-length discrepancy (R = -0.426; p = 0.011). The ISOLS scores were significantly lower in patients with a leg-length discrepancy of more than 5 cm (p = 0.005). Conclusion: Young age and complications were linked to an unfavourable functional prognosis. Leg-length correction was insufficient, especially in very young children, resulting in decreased function of the affected limb. Limb-sparing surgery for these children remains a considerable challenge.

Development of an Artificial Intelligence System for Distinguishing Malignant from Benign Soft Tissue Tumors Using Contrast-Enhanced MR Images.

INTRODUCTION: The integration of artificial intelligence (AI) into orthopedics has enhanced the diagnosis of various conditions; however, its use in diagnosing soft-tissue tumors remains limited owing to its complexity. This study aimed to develop and assess an AI-driven diagnostic support system for magnetic resonance imaging (MRI)-based soft-tissue tumor diagnosis, potentially improving accuracy and aiding radiologists and orthopedic surgeons. METHODS: Experienced orthopedic oncologists and radiologists annotated 720 images from 77 cases (41 benign and 36 malignant soft-tissue tumors). Eleven tumor subtypes were identified and classified into benign and malignant groups based on histological diagnosis. Utilizing the standard machine learning classifier pipeline, we examined and down-selected imaging protocols and their predominant radiomic features within the tumor's three-dimensional region to differentiate between benign and malignant tumors. Among the scan protocols, contrast-enhanced T1 weighted fat-suppressed images showed the most accurate classification based on radiomics features. We focused on the two-dimensional features from the largest tumor boundary surface and its neighboring slices, leveraging texture-based radiomic and deep convolutional neural network features from a pretrained VGG19 model. RESULTS: The test data comprised 44 contrast-enhanced images (22 benign and 22 malignant soft-tissue tumors) containing six malignant and five benign subtypes distinct from the training data. We compared expert and non-expert human performances against AI by assessing malignancy detection and the time required for classification. The AI model showed comparable accuracy (AUC 0.91) to that of radiologists (AUC 0.83) and orthopedic surgeons (AUC 0.73). Notably, the AI model processed data approximately 400 times faster than its human counterparts, showcasing its capacity to significantly boost diagnostic efficiency. CONCLUSION: We developed an AI-driven diagnostic support system for MRI-based soft-tissue tumor diagnosis. While additional refinement is necessary for clinical applications, our system has exhibited promising potential in differentiating between benign and malignant soft-tissue tumors based on MRI.

Out-of-pocket fertility preservation expenses: data from a Japanese nationwide multicenter survey.

BACKGROUND: The expenses related to fertility preservation or subsequent assisted reproductive treatments are significant for adolescents and young adult patients in Japan's current healthcare system. With fertility preservation becoming more widespread in developed countries, it is expected that these costs will be covered by insurance or subsidies. It is critical for patients, healthcare providers, and the government to know the costs that patients will be responsible for. In Japan, the costs of fertility preservation and subsequent assisted reproductive technology are not covered by insurance, but patients can apply for subsidies from the local and central governments if certain conditions are met. Presently, the above-mentioned costs, as well as the amount paid by the patient, vary by facility. Therefore, it is essential to ensure patients' continued access to necessary medical care despite the associated costs. METHODS: In this study, questionnaires were mailed to 186 certified fertility preservation facilities in Japan to assess patients who had undergone fertility preservation or assisted reproduction. The questionnaires were sent between October 27, 2023 and March 31, 2024, with 140 of the 186 facilities responding (response rate: 75.3%). RESULTS: Our findings show that approximately one-third of the costs was borne by the patients. CONCLUSION: Given these circumstances, sustainable pricing and insurance coverage are necessary for both patients and facilities.

Bilateral Upper Arm Granulomas Induced by Leuprorelin Acetate Injection Mimicking Malignant Soft Tissue Tumors: A Case Report.

Leuprorelin acetate is a common anticancer medication used for prostate cancer treatment. One of the local adverse reactions after leuprorelin injection is the development of reactive granulomas, typically presenting as subcutaneous nodules. In this case report, we describe a 73-year-old patient with prostate cancer who developed unusually large sized intramuscular reactive granulomas, which mimicked malignant soft tissue tumors. The patient, who had been receiving leuprorelin acetate treatment for the past 12 months, noticed painful masses in both upper arms. Based on the findings of magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography/computed tomography, a diagnosis of malignant soft tissue tumor was strongly suggested. However, further investigation through needle biopsy ultimately led us to the final diagnosis of reactive granuloma. The masses spontaneously resolved after discontinuation of leuprorelin injection. While reactive granulomas after leuprorelin injections are not rare, intramuscular cases are relatively uncommon. Despite using imaging studies as a rational initial approach in the diagnostic process, as we did in our case, their results turned out to be indistinguishable from those of malignant soft tissue tumors, thus highlighting the importance of pathological examination in confirming diagnosis, especially when a patient presents with atypical clinical manifestations.

Translational Aspects of Epithelioid Sarcoma: Current Consensus.

Epithelioid sarcoma (EpS) is an ultra-rare malignant soft-tissue cancer mostly affecting adolescents and young adults. EpS often exhibits an unfavorable clinical course with fatal outcome in ∼50% of cases despite aggressive multimodal therapies combining surgery, chemotherapy, and irradiation. EpS is traditionally classified in a more common, less aggressive distal (classic) type and a rarer aggressive proximal type. Both subtypes are characterized by a loss of nuclear INI1 expression, most often following homozygous deletion of its encoding gene, SMARCB1-a core subunit of the SWI/SNF chromatin remodeling complex. In 2020, the EZH2 inhibitor tazemetostat was the first targeted therapy approved for EpS, raising new hopes. Still, the vast majority of patients did not benefit from this drug or relapsed rapidly. Further, other recent therapeutic modalities, including immunotherapy, are only effective in a fraction of patients. Thus, novel strategies, specifically targeted to EpS, are urgently needed. To accelerate translational research on EpS and eventually boost the discovery and development of new diagnostic tools and therapeutic options, a vibrant translational research community has formed in past years and held two international EpS digital expert meetings in 2021 and 2023. This review summarizes our current understanding of EpS from the translational research perspective and points to innovative research directions to address the most pressing questions in the field, as defined by expert consensus and patient advocacy groups.

Multiple Recurrent Atypical Lipomatous Tumors/Well-Differentiated Liposarcomas and Dedifferentiated Liposarcomas Treated with Multiple Surgical Resections: A Case Report.

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLPS) is usually a solitary adipocytic tumor. ALT/WDLPS shows no potential for metastasis unless it undergoes dedifferentiation. No case of multiple ALT/WDLPS has been reported in recent years. We present a rare case of multiple recurrent liposarcomas. A 71-year-old man with a history of scrotal ALT/WDLPS at 61 years presented with multiple large tumors spread throughout the body. The patient was bedridden and severely limited in his activities of daily living (ADL) due to multiple large tumors in the trunk and lower extremities. Radiological examination revealed multiple adipocytic tumors, mainly in the soft tissues of the trunk and extremities, with several visceral lesions. Tumors were resected in stages, starting with large tumors directly related to disability. Repeated palliative resections improved the patient's ADL; he regained ambulation and was discharged 18 months after admission. Twelve surgeries were performed to remove 44 adipocytic tumors from the testis, left chest wall, perigastric area, ileum, left inguinal region, both buttocks, thighs, and lower legs. Histological examination revealed dedifferentiated components in five tumors, while 39 tumors were diagnosed as ALT/WDLPS. At the age of 76 years, the patient developed an unresectable dedifferentiated liposarcoma between the heart and aorta, leading to fatality at 79 years. The patient's clinical course suggested multiple metastases of ALT/WDLPS of scrotal origin or ALT/WDLPS of multicentric origin. Although multicentric ALT/WDLPS or ALT/WDLPS metastases are rare, they should be considered when multiple large adipocytic tumors are found throughout the body. Despite the presence of numerous large malignant tumors, surgical treatments of the lesions can improve ADL and prolong life if the tumors are of low-grade malignancy.

A multicentre retrospective study on extra-thoracic solitary fibrous tumour: preoperative MRI findings predict intraoperative findings and postoperative prognosis.

OBJECTIVE: The present study investigated the relationships between the preoperative and operative findings of solitary fibrous tumour (SFT) and between preoperative findings and prognosis. METHODS: We reviewed 50 SFT patients treated at our musculoskeletal oncology hospital group. We analyzed preoperative clinical findings, particularly MRI imaging findings, and intraoperative information as well as the relationship between preoperative findings and outcomes. RESULTS: Mean age was 48.9 years and the mean follow-up was 51.8 months. Prior to surgery, needle biopsy was performed on 27 patients and open biopsy on 14. T2-weighted images showed a high signal intensity in 24 patients and heterogeneous signal intensity in 20. Tumours had polylobular contours in 17 patients and smooth and round contours in 27. Collateral feeding vessels were detected in 22 patients. Gd-enhanced MRI was performed on 23 patients, and showed 15 with homogeneous enhancement and 8 with heterogeneous enhancement. Surgical times were significantly longer in patients with a retroperitoneal origin, a tumour of 10 cm or more, and polylobular-type tumours. Intraoperative blood loss was significantly greater in patients with a retroperitoneal origin and heterogeneous Gd-MRI-enhanced tumours. In histopathological evaluations, surgical margins were positive in 12 patients. Local recurrence was observed in one patient. Distant metastasis was noted in eight patients, four of whom had pulmonary metastases. Positive surgical margins were more common in polylobular-type tumours. Distant metastases were more likely to appear in patients with observable collateral feeding vessels and heterogeneous Gd-MRI enhancement. CONCLUSION: The present results suggest that preoperative clinical findings in SFT patients predict longer surgical times and the risk of increased intraoperative blood loss. Moreover, the risk of a positive surgical margin and postoperative distant metastases may be predicted based on preoperative MRI.

Additional Wide Resection of Infantile Dermatofibrosarcoma Protuberans after Unplanned Excision: A Case Report.

Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive intermediate soft tissue neoplasm that occurs in the dermis. DFSP generally occurs in young to middle-aged adults and rarely in infancy. Because of its extreme rarity, DFSP is difficult to diagnose and treat, especially when it occurs in infancy. In this paper, we reported a case of infantile DFSP in which we performed additional wide resection with a 3-cm horizontal margin for a mass that had previously undergone unplanned excision. No tumor recurrence has been seen for 3 years postoperatively. We suggest that the possibility of DFSP should always be considered when an enlarging superficial mass is identified on the trunk, even in an infant. Additionally, radical local treatment is as important for DFSP in infancy as it is for DFSP in adults, even after unplanned excision.

Protocol for the 2ND-STEP study, Japan Clinical Oncology Group study JCOG1802: a randomized phase II trial of second-line treatment for advanced soft tissue sarcoma comparing trabectedin, eribulin and pazopanib.

BACKGROUND: Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS. METHODS: The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial. DISCUSSION: This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials ( jRCTs031190152 ) on December 5, 2019.

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG).

BACKGROUND: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. METHODS: Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. RESULTS: A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. CONCLUSIONS: The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.

Intramedullary osteoid osteoma in the humerus of a toddler-A case report and review of the literature.

Osteoid osteoma (OO) is a benign osteoblastic tumor characterized by nocturnal pain that responds well to non-steroidal anti-inflammatory drugs. This condition commonly affects adolescents and young adults, and patients between 5 and 24 years of age account for 85% of all OO cases; it occurs very rarely in patients under 5 years old. Tumors often occur in the cortical bone in the diaphysis and metaphysis of the appendicular skeleton and are more common in the lower extremities than upper extremities. Here, we present an extremely rare case of intramedullary OO that arose in the proximal metaphysis of the humerus in a 2-year-old boy, which mimicked subacute osteomyelitis on imaging studies. We also conducted a retrospective literature review and found that the intramedullary location was fairly common in very young patients (<6 years old) with OO.

Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306.

BACKGROUND: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS). METHODS: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS. RESULTS: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD. CONCLUSIONS: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk. CLINICAL TRIAL REGISTRATION: jRCTs031180003.