Exceptional response to neoadjuvant targeted therapy with the selective RET inhibitor selpercatinib in RET-fusion-associated sarcoma.

With the increasing use of next-generation sequencing, highly effective targeted therapies have been emerging as treatment options for several cancer types. Recurrent gene-fusions have been recognized in sarcomas; however, options for targeted therapy remain scarce. Here, we describe a case of a sarcoma, associated with a RET::TRIM33-fusion gene with an exceptional response to a neoadjuvant therapy with the selective RET inhibitor selpercatinib. Resected tumor revealed subtotal histopathologic response. This is the first report of successful targeted therapy with selpercatinib in RET-fusion-associated sarcomas. As new targeted therapies are under development, similar treatment options may become available for sarcoma patients.

Clinical performance of the Femoral Neck System within 1 year in 125 patients with acute femoral neck fractures, a prospective observational case series.

INTRODUCTION: Osteosynthesis of femoral neck fractures (FNFs) is an important treatment option, especially for younger patients. We aimed to assess the rate of early implant-related complications in FNF osteosynthesis using the Femoral Neck System (FNS). PATIENTS AND METHODS: Consecutive patients diagnosed with displaced or nondisplaced FNFs were treated with FNS in this prospective, observational, multicenter investigation. Patients were followed up for minimally 3 months and up to 12 months if radiologic bone union and no pain was not achieved beforehand. Predefined treatment-related adverse events (AEs, defined as implant failure, loss of reduction, iatrogenic fractures, deep infection, and surgical revision), radiologic bone union, and patient-reported Harris hip score (HHS) and EQ-5D-5L index score were assessed. RESULTS: One hundred and twenty-five patients were included in the study. Thirty-eight (30.4%) fractures were displaced (Garden III and IV), and 37 (29.6%) were vertical fractures (Pauwels type III). Predefined treatment-related AE rate at 3 months was 8 patients, 6.4% (95% CI, 2.8-12.2), and at 12 months, 11 patients, 8.8% (95% CI, 4.5-15.2). Cumulative incidences of bone union were 68% at 3 months, 90% at 6 months, and 98% at 12 months. The mean changes of HHS and EQ-5D-5L index score between preinjury and at 12 months were -7.5 (95% CI, [ - 21.1] to [6.2]) and - 0.03 (95% CI, [ - 0.21] to [0.15]), respectively; neither were statistically significant. CONCLUSION: The current study on osteosynthesis of FNFs with the FNS resulted in treatment-related complication rates of 6.4% (95% CI, 2.8-12.2) at 3 months and 8.8% (95% CI, 4.5-15.2) at 12 months. On average, patients returned to preinjury function and quality of life. The current study may also indicate that the conventional wisdom of treating stable FNF in patients aged between 60 and 80 years with osteosynthesis may need to be reconsidered. REGISTRATION: The study is registered with ClinicalTrials.gov (registration number: NCT02422355).

The use of denosumab in the setting of acute pathological fracture through giant cell tumour of bone.

BACKGROUND: Denosumab (XgevaTM) is a fully human antibody to RANK-Ligand, an important signal mediator in the pathogenesis of giant cell tumour of bone (GCTB). The use of denosumab in the treatment of GCTB has changed the way in which these tumours are managed over the past years. CASE PRESENTATION: Described is the case of an acute fracture through a GCTB of the distal radius of a fit and well 32-year-old, non-smoking, female patient following a simple fall onto her outstretched, dominant hand. The aim was to enable joint sparing management for the patient, as opposed to an acute fusion procedure of the carpus. The patient underwent percutaneous k-wire fixation with application of plaster and immediate commencement with denosumab to halt the activity of the GCTB. Bone healing was rapid; plaster and k-wires were removed after 6 weeks. At 6 months denosumab, was ceased and an open curettage and grafting procedure of the tumour bed was undertaken (using MIIG X3, Wright Medical, aqueous calcium sulphate as graft material). CONCLUSIONS: The use of denosumab in the acute setting of pathological fracture through giant cell tumour of bone allowing joint salvage has not been previously described. The treatment was well tolerated and functional outcomes are excellent, with very promising 4-year follow-up. This novel approach may allow for more joint sparing strategies in the future for other patients in this difficult situation. Further cases will need to be gathered to establish this technique as a suitable treatment pathway.

NUT midline carcinoma in a young pregnant female: a case report.

INTRODUCTION: The NUT midline carcinoma is a rare tumor mostly reported in the midline of upper aerodigestive tract and mediastinum. Children as well as adolescents are affected without a gender distribution. A standard treatment is not established. So far, there exists no reported case of a pregnant female suffering from NUT midline carcinoma with musculoskeletal manifestation. CASE PRESENTATION: A 34-year-old woman was referred to our outpatient clinic by the general practitioner during her 31st week of pregnancy suffering from shoulder pain and dyspnea. So far, dyspnea was interpreted as a typical pregnancy-related symptom. However, a chest X-ray showed a tumor mass in the right lung in close relation to the scapula. Further examinations found metastases in different areas of the body. No pregnancy-related complications were detected by obstetric examination. After an interdisciplinary perinatal case discussion, cesarean section was directly followed by an open biopsy of the right side scapula tumor lesion. A NUT midline carcinoma was diagnosed by immunohistochemistry. Due to disseminated tumor disease in multiple non-resectable locations, a palliative systemical chemotherapy was started by the oncological outpatient clinic. CONCLUSION: This report presents the case of the very rare NUT midline carcinoma under pregnancy which made interdisciplinary case discussions indispensable for therapy planning.

Factors influencing quality of life, function, reintegration and participation after musculoskeletal tumour operations.

BACKGROUND: The number of people living with soft-tissue and bone sarcomas is increasing due to improved individual therapy and changes in demographics. At present, there are no recommendations for psychological co-treatment, occupational and social reintegration following the treatment of soft tissue and bone sarcomas. METHODS: Seventy-four patients, 42 males and 32 females, aged between 18 and 80 years (54.58 ± 16.99 yr.) with soft-tissue (62) and bone sarcomas (12) were included to answer five standardized and one personal questionnaire regarding quality of life, function, reintegration and participation after surgical treatment. RESULTS: A number of tumour-specific and patient-specific factors were identified that affected the therapeutic outcome. Patients with sarcoma of the lower extremity described poorer mobility. Patients who underwent amputation reported a higher anxious preoccupation. Patients with a higher range of education were less fatalistic and avoiding. The size of tumours or additive radiation therapy did not affect the post-therapeutic quality of life, coping and function. There was a good correlation between anxiety and depression with occupational reintegration, function, quality of life and coping. CONCLUSION: Patients with sarcomas of the lower limb have a higher demand for postoperative rehabilitation and need more help in the postoperative occupational reintegration. Furthermore patients that underwent limb-preserving operations reported better postoperative function and quality of life. Risk assessment using patient-specific factors and an intensive psychological co-treatment may have a large role in the co-treatment of patients from the beginning of their cancer therapy.

Acute atraumatic carpal tunnel syndrome due to flexor tendon rupture following palmar plate osteosynthesis in a patient taking rivaroxaban.

INTRODUCTION: Few case reports describe the development of a hematoma under oral anticoagulation as the cause of an atraumatic carpal tunnel syndrome. CASE REPORT: A 76 years old woman presented an acute atraumatic carpal tunnel syndrome of her left hand under oral anticoagulation with rivaroxaban due to atrial fibrillation. 12 years ago, palmar plate osteosynthesis of a distal radius fracture had been performed on the affected wrist. Open decompression of the carpal canal was performed due to persistent severe pain under intense pain therapy and progressive neurological symptoms. The cause of the pain was a hematoma due to a rupture of the flexor pollicis longus and the second flexor digitorum profundus tendon with concomitant synovitis at the plate's distal rim. After decompression, pain relieved and neurological deficits improved rapidly. DISCUSSION: Ruptures of the flexor tendons occur in palmar plate osteosynthesis in up to 1.5% in the long term postoperative course. Very distal plate positions, like in this case, increase that risk. Under anticoagulation, the rupture induced a hematoma increasing local pressure resulting in an acute carpal tunnel syndrome. Acute nerve compression syndromes should be treated surgically without delay. CONCLUSION: Therapy with anticoagulants may increase hematoma after tendon rupture, thus supporting the development of an atraumatic acute carpal tunnel syndrome and complicating the surgical therapy. Hardware removal after fracture healing should be advised in patients with Soong grade 2 plate positions especially those taking anticoagulants.

Desmoid Tumor of the Popliteal Fossa during Pregnancy.

Desmoid tumors are fibroblastic neoplasms that have an intermediate behavior with a highly aggressive infiltrative growth arising from deep muscle or aponeurosis. We present the case of a 34-year-old woman that developed a painless mass in the right popliteal fossa during pregnancy after intracytoplasmic sperm injection and hormonal therapy. The MRI scan showed a hyperintense mass of 6,7 cm × 4,7 cm × 3,8 cm surrounding the lateral head of the gastrocnemius muscle. The open biopsy was done one week after delivery, and the histology showed a desmoid tumor. We performed the resection one week later and found the common peroneal nerve completely surrounded by the tumor. The close resection due to the neurolysis was the reason why an adjuvant radiation with 56 Gy was done. The last clinical examination, 18 month later, did not show any signs of recurrence and an excellent functional outcome. This case demonstrates the possible influences of pregnancy and hormonal therapy on the evolution of desmoid tumors.