Larotrectinib in a NTRK-rearranged soft tissue sarcoma in the neoadjuvant setting: A case report.
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SUBMITTER: Percy C
PROVIDER: S-EPMC7981750 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundMetachronous osteosarcoma is a rare form of osteosarcoma. The occurrence of metachronous tumor in soft tissue is exceedingly rare. The pathogenesis of metachronous osteosarcoma, as to whether it represents multiple true primaries or metastatic disease, is still obscure.Case presentationA 49-year-old Indian man presented with progressively increasing swelling in his left hand of 2 months' duration. An X-ray showed a soft tissue lesion. Contrast-enhanced computed tomography showed a soft tissue mass lesion, with peripheral enhancement and central necrotic areas in radial palmar soft tissue overlying second metacarpophalangeal region with no obvious bony osteolysis. Possibilities of acute abscess, resolving hematoma, or aggressive soft tissue mass lesion were suggested. An incision biopsy showed morphological features of epithelioid osteosarcoma, which was confirmed on immunohistochemistry. A detailed history revealed that our patient was diagnosed as having osteosarcoma of his right leg 3 years previously. Based on history, radiology, morphology, and immunohistochemistry, a final diagnosis of extraskeletal (soft tissue) epithelioid osteogenic sarcoma of the left hand occurring as a metachronous tumor 3 years after diagnosis of primary osteosarcoma in the right leg was given.ConclusionThis is probably the first reported case of extraskeletal (soft tissue) epithelioid osteosarcoma occurring as a metachronous tumor 3 years after diagnosis of primary osteosarcoma in the right leg. The prognosis of metachronous skeletal osteosarcoma is poor as compared to that of relapse limited to lungs. In late metachronous osteosarcoma, combined-modality therapy comprising surgery and aggressive chemotherapy may affect long-term survival. Lifelong follow-up of surviving patients with osteosarcoma is necessary and if metachronous osteosarcoma is discovered, it should be treated with curative intent.
| S-EPMC6507060 | biostudies-literature
Project description:IntroductionCapicua transcriptional repressor (CIC)-DUX4 rearranged sarcoma is a subtype of CIC-rearranged sarcomas composed of undifferentiated Wilms' tumor 1 (WT1)+, CD99+ round cells with recurrent CIC gene rearrangement. The diagnosis of CIC-rearranged sarcoma remains challenging, and the prognosis of CIC-rearranged sarcomas is poor.Case presentationIn this report, we described a case of CIC-DUX4 rearranged sarcoma presenting in the skin, expressing WT1 and CD99 in a dot-like pattern. In addition, the assessment of genomic alterations using genome panel testing was useful to confirm the accurate diagnosis.ConclusionOur present case suggests that widespread use of genomic panel testing in the future may lead to early treatment and improve the prognosis of CIC-rearranged sarcomas.
| S-EPMC11249449 | biostudies-literature
Project description:NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) are rare soft tissue tumor molecularly characterized by NTRK gene rearrangement, which occurs mostly in children and young adults, and rarely in adults. The abnormal tumor located in superficial or deep soft tissues of human extremities and trunk mostly, and rarely also involves abdominal organs. In this case, we report a malignant NTRK-RSCN that occurred in the pelvic region of an adult. The patient was found to have a large tumor in the pelvic region with a pathological diagnosis of infiltrative growth of short spindle-shaped tumor cells with marked heterogeneity. Immunohistochemistry of this patient showed positive vimentin, pan-TRK and Ki67 (approximately 60%) indicators with negative S100, Desmin and DOG1. Molecular diagnosis revealed c-KIT and PDGFRα wild type with TPM3-NTRK1 fusion, unfortunately this patient had a rapidly progressive disease and passed away. This case highlights the gene mutation in the molecular characteristics of NTRK-RSCNs, and the significance of accurate molecular typing for the diagnosis of difficult cases.
| S-EPMC10864579 | biostudies-literature
Project description:Soft-tissue sarcomas (STSs) are a heterogeneous group of tumors, which accounts for 1-2% of adult cancers worldwide. Despite quite a few reports on traumatic events followed by STS formation, the link between the two events remains a point of controversy. In this paper, we present the case of a young patient who had a rhabdomyosarcoma in the lower extremity, which had developed in the same location where the patient was wounded by a gunshot 9 years earlier. X-ray and CT scans clearly showed metal fragments in the area of sarcoma formation. The patient underwent neoadjuvant chemotherapy treatment, to which the tumor was, unfortunately, unresponsive. Therefore, the patient was referred to below-knee amputation of the injured leg. There are several possible etiological factors for sarcoma development in this patient, including tissue damage and inflammation, as well as the presence of metal fragments in the tissue and the limb's exposure to radiation during multiple imaging tests. Here, we will discuss the potential influence wielded by the injury itself, as well as its complications and its medical management on the formation of the sarcoma, in light of the current literature.
| S-EPMC5483586 | biostudies-other
Project description:BackgroundNeoadjuvant radiotherapy (RT) for soft tissue sarcoma (STS) is widely used abroad, but rarely reported in China. We assessed the preliminary clinical outcomes of preoperative RT followed by surgery in patients with STS.MethodsA total of 19 patients (14 male, 5 female) with intermediate- or high-grade primary STS were treated with neoadjuvant RT in 2-Gy fractions over 25 sessions for a total dose of 50 Gy. Surgical resection was then performed. The pathologic specimens were reviewed for percentage of residual tumor cells. And the skin complications, wound complications and local recurrence and distant metastasis were also evaluated.ResultsAfter neoadjuvant RT, 2 patients had progressive disease (PD), 6 showed a partial remission (PR), and 11 demonstrated stable disease (SD). The objective response rate (ORR) was 31.6%, and the disease control rate (DCR) was 89.5%. The median follow-up was 14.3 months (11.9-24.7 months). Six patients (31.6%) had wound complications: 3 cases of epidermal complications and 3 of severe complications (15.8%) comprising 2 cases of skin flap necrosis, and 1 case of local hematoma. The European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) histopathological response score was used to evaluate the post-RT response. A total of 9 patients (47.4%) achieved pathological complete remission (pCR). No recurrence was found, but metastasis occurred in 2 patients (10.5%) in the preliminary follow-up.ConclusionsNeoadjuvant RT for STS has a quietly high DCR and pathological remission rate. Surgical wound complications can be controlled after neoadjuvant RT.
| S-EPMC9096360 | biostudies-literature
Project description:Hyperprogression associated with immunotherapy has been reported previously with melanoma, non-small cell lung cancer (NSCLC), renal, and urothelial cancers but not with sarcoma. A 63-year old man with a biopsy-proven, localized 13 cm high-grade myxoid/round cell liposarcoma of the thigh was treated with concurrent, neoadjuvant checkpoint inhibitor immunotherapy and radiotherapy. After his subsequent wide surgical resection, he developed small hepatic lesions that rapidly progressed and caused his death, raising the possibility of hyperprogression in this entity.
| S-EPMC7358953 | biostudies-literature
Project description:To investigate the clinical efficacy of neoadjuvant chemotherapy in the treatment of extremity soft tissue sarcomas (STSs). We retrospectively analyzed 28 patients with extremity STS that received 2 cycles of preoperative and 6 cycles of postoperative neoadjuvant chemotherapy between May 2009 and June 2012. Chemotherapy comprised intravenous cisplatin (DDP) (120? mg/m(2), for 1 day), followed 1 week later with 5 days 2? g/m(2) ifosfamide (IFO) and 3 days 30 ?mg/m(2) adriamycin (ADM). CT scans of the lungs and X-ray films of the lesion sites were reviewed. Eighteen patients were treated for primary tumor and 10 for tumor recurrence. Overall tumor diameter ranged from 8 to 30? cm based on body surface measurement. A total of 224 cycles of chemotherapy were carried out and patients were followed up for 12 to 59 months. Twenty-five patients underwent wide resection surgery (89.2%), and 3 underwent amputation (10.7%). Disease-free survival was realized in 20 patients and 3 patients survived with tumors. Two-year disease-free survival rate was 71.4%, and overall 2-year survival rate was 82.1%. Postoperative metastases were observed in 5 patients, and all died of lung metastases. Postoperative recurrence was observed in 4 patients (including 1 patient occurred metastases later). Tumor size was reduced by 30%?±?11.3% on average after the preoperative chemotherapy, and was reduced by 43%?±?7.8% in 22 patients with tumors >15 ?cm in the diameter. Twelve patients achieved partial remission, 14 stable disease and 2 experienced progressive disease. Objective response rate was 42.9%. Disease control rate was 92.9%. Chemotherapy was well tolerated in all the patients. Main adverse reactions were transient and resolved after chemotherapy. Neoadjuvant chemotherapy is effective in the treatment of extremity STS.
| S-EPMC5291584 | biostudies-literature
Project description:Historically, patients with localized soft tissue sarcomas (STS) of the extremities would undergo limb amputation. It was subsequently determined that the addition of radiation therapy (RT) delivered prior to (neoadjuvant) or after (adjuvant) a limb-sparing surgical resection yielded equivalent survival outcomes to amputation in appropriate patients. Generally, neoadjuvant radiation offers decreased volume and dose of high-intensity radiation to normal tissue and increased chance of achieving negative surgical margins-but also increases wound healing complications when compared to adjuvant radiotherapy. This review elaborates on the current neoadjuvant/adjuvant RT approaches, wound healing complications in STS, and the potential application of novel radioprotective agents to minimize radiation-induced normal tissue toxicity.
| S-EPMC7465163 | biostudies-literature
Project description:PurposeWhether the therapeutic response of soft-tissue sarcoma to neoadjuvant treatment is predictive for clinical outcomes is unclear. Given the rarity of this disease and the confounding effects of chemotherapy, this study analyzes whether a favorable pathologic response (fPR) after neoadjuvant radiation therapy (RT) alone is associated with clinical benefits.Methods and materialsAn institutional review board-approved retrospective review was conducted on a database of patients with primary soft-tissue sarcoma treated at our institution between 1987 and 2015 with neoadjuvant RT alone followed by surgical resection. Time-to-event outcomes estimated with a Kaplan-Meier analysis included overall survival, progression-free survival (PFS), locoregional control, and distant control (DC). Cox regression analyses were performed to determine prognostic variables associated with clinical outcomes.ResultsOf the overall cohort of 315 patients, 181 patients (57%) were included in the primary analysis with documented pathologic necrosis (PN) rates (mean: 59%) and a median follow up from diagnosis of 48 months (range, 4-170 months). The median neoadjuvant RT dose was 50 Gy (range, 40-60 Gy), and the majority of patients had negative surgical margins (79%). Only 35 patients (19%) achieved a fPR (PN ≥95%), which was associated with a higher R0 resection rate (94% vs. 75%; P = .013), a significant 5-year PFS benefit (74% vs. 43%; P = .014), and a nonsignificant 5-year DC benefit (76% vs. 62%; P = .12) compared with PN <95%. On multivariable analysis, fPR was an independent predictor for PFS (hazard ratio: 0.47; 95% confidence interval, 0.25-0.90; P = .022).ConclusionsAchieving fPR with neoadjuvant RT alone is associated with a higher R0 resection rate and possible DC benefit, translating into a significant improvement in PFS. Further studies to improve pathologic response rates and prospectively validate this endpoint are warranted.
| S-EPMC9723307 | biostudies-literature
Project description:Background:Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection. Methods:Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation. Biomarkers were measured using automated computerized imaging (AQUA or ACIS). Expression was correlated with disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). Results:Specimens from 60 patients included 23 pretreatment (PRE), 40 posttreatment (POST), and 12 matched pairs (MPs). In the MP set, CAIX, GLUT1, and PARP1 expression significantly decreased following neoadjuvant therapy, but p53 nuclear/cytoplasmic (N/C) ratio increased. In the PRE set, no biomarker expression was associated with DFS, DDFS, or OS. In the POST set, increased p53 N/C ratio was associated with a significantly decreased DFS and DDFS (HR 4.13, p=0.017; HR 4.16, p=0.016), while increased ERCC1 and XPF expression were associated with an improved DFS and DDFS. No POST biomarkers were associated with OS. Conclusions:PRE biomarker expression did not predict survival outcomes. Expression pattern changes after neoadjuvant chemoradiation supports the concepts of tumor reoxygenation, altered HIF-1? signaling, and a p53 nuclear accumulation DNA damage response. Clinical Trial Registration:NRG Oncology RTOG 9514 is registered with ClinicalTrials.gov. The ClinicalTrials.gov Identifier is NCT00002791.
| S-EPMC5851029 | biostudies-literature