Prolonged response to sorafenib in a patient with refractory metastatic osteosarcoma and a somatic PDGFRA D846V mutation

2018 ◽  
Vol 66 (1) ◽  
pp. e27493 ◽  
Author(s):  
Amy E. Armstrong ◽  
David O. Walterhouse ◽  
Patrick J. Leavey ◽  
Jennifer Reichek ◽  
Amy L. Walz
Keyword(s):  
Metastatic Osteosarcoma ◽  
Prolonged Response

Chest case of the day. Metastatic osteosarcoma to lung.

1990 ◽  
Vol 154 (6) ◽  
pp. 1321-1323
Author(s):  
P W Goose ◽  
M A Stull ◽  
H L Twigg
Keyword(s):  
Metastatic Osteosarcoma

scholarly journals A possible interaction between favipiravir and methotrexate: Drug-induced hepatotoxicity in a patient with osteosarcoma

2021 ◽  
pp. 107815522110313
Author(s):  
Emre Demir ◽  
Osman Sütcüoğlu ◽  
Beril Demir ◽  
Oktay Ünsal ◽  
Ozan Yazıcı
Keyword(s):  
Drug Interactions ◽  
Toxic Hepatitis ◽  
Antiviral Agents ◽  
Antiviral Agent ◽  
Aldehyde Oxidase ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Drug Induced ◽  
Metastatic Osteosarcoma ◽  
Grade 3

Introduction Favipiravir is an antiviral agent that is recently used for SARS-CoV2 infection. The drug-drug interactions of favipiravir especially with chemotherapeutic agents in a patient with malignancy are not well known. Case report The patient diagnosed with metastatic osteosarcoma was given high dose methotrexate treatment, and favipiravir was started on the third day of the treatment with suspicion of SARS-CoV2 infection. Grade 3 hepatotoxicity developed after favipiravir. Management & outcome: The acute viral hepatitis panel and autoimmune liver disease panel were negative. The ultrasound of the abdomen was unremarkable for any hepatobiliary pathology. The all viral and hepatobiliary possible etiological factors were ruled out. The patient’s liver enzymes increased just after (12 hours later) the initiation of favipiravir, and we diagnosed toxic hepatitis caused by favipiravir-methotrexate interaction. Therefore, methylprednisolone 1 mg/kg dose was started for a presumed diagnosis of toxic hepatitis. Hepatotoxicity completely regressed after favipiravir was discontinued. Discussion Favipiravir may inhibit methotrexate elimination by inhibiting aldehyde oxidase and its sequential use may cause hepatotoxicity in this case. The clinicians should keep in mind possible drug interactions while using new antiviral agents against SARS-CoV2 like favipiravir.

scholarly journals Complete remission of metastatic osteosarcoma using combined modality therapy: a retrospective analysis of unselected patients in China

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xiaowei Li ◽  
Zuli Zhou ◽  
Hongqing Zhuang ◽  
...  
Keyword(s):  
Pulmonary Metastases ◽  
Local Therapy ◽  
Hypofractionated Radiotherapy ◽  
Study Cohort ◽  
Sufficient Information ◽  
Progression Rate ◽  
Entire Study ◽  
Pulmonary Lesions ◽  
Metastatic Osteosarcoma ◽  
Significant Difference

Abstract Background Complete surgical remission (CSR) is the best predictor of overall survival (OS) for patients with metastatic osteosarcoma. However, metastasectomy has not been widely implemented in China in the last decade due to various factors, and instead, most physicians choose hypofractionated radiotherapy to treat pulmonary lesions. This study aimed to retrospectively evaluate the outcomes of different local treatments for pulmonary lesions and identify the best local therapy strategies for these patients. Methods We reviewed the clinical courses of osteosarcoma patients with pulmonary metastases who were initially treated in two sarcoma centres in Beijing, China, from June 1st, 2009, to March 26th, 2020. With a median follow-up of 32.4 (95% confidence interval (CI): 30.8, 36.1) months, a total of 127 patients with 605 pulmonary nodules, all of whom had received local therapy and firstly achieved CSR or complete radiated/metabolic remission (CRR), were included in the analysis. A total of 102 patients with 525 nodules were initially diagnosed with resectable lung metastases, while 25 patients had 80 indeterminate nodules at presentation and relapsed with pulmonary metastases within 6 months after the completion of adjuvant chemotherapy. Results Eighty-eight of 127 (69.3%) patients had fewer than 5 nodules at the time of local therapy, with 48 of 127 (37.8%) located in the unilateral pleura. No patient underwent thoracotomy, and 42 of 127 patients (85 nodules) received video-assisted thoracoscopic surgery (VATS). In addition, 79 of 127 patients (520 nodules) received hypofractionated stereotactic body radiotherapy (RT), such as Gamma Knife radiosurgery or CyberKnife radiosurgery. The twelve-month event-free survival (EFS) (from local therapy to progression) rate of this entire study cohort was 35.6% (95% CI: 26.8, 44.4%), without a significant difference between the two groups (44.7% for VATS vs. 28.4% for RT, P = 0.755). Radiation-induced pneumonitis was observed in 62 of 86 (72.1%) patients, with one patient (1/86, 1.2%) in grade 4. Conclusions Our past data showed a similar prognosis with the use of hypofractionated radiotherapy and VATS for the treatment of pulmonary metastasis and no inferiority to thoracotomy regarding historical outcomes. Currently, high-resolution chest computed tomography (CT) provides sufficient information on nodules, and less invasive modalities can thus be considered for treatment.

scholarly journals Pathways of immune exclusion in metastatic osteosarcoma are associated with inferior patient outcomes

2021 ◽  
Vol 9 (5) ◽  
pp. e001772
Author(s):  
John A Ligon ◽  
Woonyoung Choi ◽  
Gady Cojocaru ◽  
Wei Fu ◽  
Emily Han-Chung Hsiue ◽  
...  
Keyword(s):  
T Cell ◽  
Patient Outcomes ◽  
Immune Checkpoint ◽  
Tumor Antigens ◽  
Current Therapy ◽  
Normal Lung ◽  
Primary Bone Tumors ◽  
Metastatic Osteosarcoma ◽  
Immune Exclusion ◽  
Successful Immunotherapy

BackgroundCurrent therapy for osteosarcoma pulmonary metastases (PMs) is ineffective. The mechanisms that prevent successful immunotherapy in osteosarcoma are incompletely understood. We investigated the tumor microenvironment of metastatic osteosarcoma with the goal of harnessing the immune system as a therapeutic strategy.Methods66 osteosarcoma tissue specimens were analyzed by immunohistochemistry (IHC) and immune markers were digitally quantified. Tumor-infiltrating lymphocytes (TILs) from 25 specimens were profiled by functional cytometry. Comparative transcriptomic studies of distinct tumor-normal lung ‘PM interface’ and ‘PM interior’ regions from 16 PMs were performed. Clinical follow-up (median 24 months) was available from resection.ResultsIHC revealed a statistically significantly higher concentration of TILs expressing immune checkpoint and immunoregulatory molecules in PMs compared with primary bone tumors (including programmed cell death 1 (PD-1), programmed death ligand 1 (PD-L1), lymphocyte-activation gene 3 (LAG-3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), and indoleamine 2,3-dioxygenase (IDO1). Remarkably, these lymphocytes are excluded at the PM interface compared with PM interior. TILs from PMs exhibited significantly higher amounts of PD-1 and LAG-3 and functional cytokines including interferon-γ (IFNγ) by flow cytometry. Gene expression profiling further confirmed the presence of CD8 and CD4 lymphocytes concentrated at the PM interface, along with upregulation of immunoregulatory molecules and IFNγ-driven genes in the same region. We further discovered a strong alternatively activated macrophage signature throughout the entire PMs along with a polymorphonuclear myeloid-derived suppressor cell signature focused at the PM interface. Expression of PD-L1, LAG-3, and colony-stimulating factor 1 receptor (CSF1R) at the PM interface was associated with significantly worse progression-free survival (PFS), while gene sets indicative of productive T cell immune responses (CD8 T cells, T cell survival, and major histocompatibility complex class 1 expression) were associated with significantly improved PFS.ConclusionsOsteosarcoma PMs exhibit immune exclusion characterized by the accumulation of TILs at the PM interface. These TILs produce effector cytokines, suggesting their capability of activation and recognition of tumor antigens. Our findings suggest cooperative immunosuppressive mechanisms in osteosarcoma PMs including immune checkpoint molecule expression and the presence of immunosuppressive myeloid cells. We identify cellular and molecular signatures that are associated with patient outcomes, which could be exploited for successful immunotherapy.

scholarly journals Metastatic osteosarcoma of craniovertebral junction with cervicalgia and torticollis an a pediatric patient

2021 ◽  
Vol 24 ◽  
pp. 101059
Author(s):  
Valentina Baro ◽  
Elisa Garbin ◽  
Luca Sartori ◽  
Samuel L Caliri ◽  
Giulia M Furlanis ◽  
...  
Keyword(s):  
Pediatric Patient ◽  
Craniovertebral Junction ◽  
Metastatic Osteosarcoma

scholarly journals Continuous Tunnelled Femoral Nerve Block for Palliative Care of a Patient with Metastatic Osteosarcoma

2010 ◽  
Vol 38 (3) ◽  
pp. 563-565 ◽  
Author(s):  
H. L. Pacenta ◽  
R. N. Kaddoum ◽  
L. A. Pereiras ◽  
E. J. Chidiac ◽  
L. L. Burgoyne
Keyword(s):  
Palliative Care ◽  
Nerve Block ◽  
Femoral Nerve Block ◽  
Femoral Nerve ◽  
Metastatic Osteosarcoma

Prolonged response of skeletal muscle in the absence of penetrating anions

1960 ◽  
Vol 198 (2) ◽  
pp. 289-299 ◽  
Author(s):  
Gertrude Falk ◽  
Jorge F. Landa
Keyword(s):  
Action Potentials ◽  
Critical Concentration ◽  
Relaxation Oscillations ◽  
Plateau Phase ◽  
Slow Oscillations ◽  
Mechanical Responses ◽  
External Potassium ◽  
Prolonged Response ◽  
Plateau Level ◽  
Potassium Addition

Replacement of Ringer's chloride by a variety of nonpenetrating anions results in prolonged electrical and mechanical responses of muscle to stimulation. The ‘negative after-potential’ is characterized by a slowly increasing secondary depolarization which reaches a stable plateau lasting as long as 2 minutes. After-discharge frequently occurs during early depolarization. In most fibers repolarization is relatively abrupt, but in some, slow oscillations resembling relaxation oscillations arise following the plateau, grow gradually in amplitude and, only when they are of sufficient amplitude, does the membrane repolarize. Prolonged depolarization can still be produced when the spike has failed. At times, fibers may respond with short-duration action potentials, but may be primed to give prolonged responses by previous stimuli or by increase of external potassium. Addition of chloride has no effect below a critical concentration. Reduction of sodium to 25% of normal does not change plateau level or duration. Duration of the plateau phase is decreased by potassium.

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