scholarly journals Successful Treatment of Advanced Intrahepatic Cholangiocarcinoma With a High Tumor Mutational Burden and PD-L1 Expression by PD-1 Blockade Combined With Tyrosine Kinase Inhibitors: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Ze Zhang ◽  
Wenwen Zhang ◽  
Hongguang Wang ◽  
Bingyang Hu ◽  
Zhanbo Wang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Intrahepatic Cholangiocarcinoma ◽  
Kinase Inhibitors ◽  
Histopathological Examination ◽  
Stage Iv ◽  
Radical Resection ◽  
Mutational Burden ◽  
First Case ◽  
Tumor Mutational Burden

Advanced intrahepatic cholangiocarcinoma (iCCA) is not suitable for surgical treatment. Guided by the concept of precision medicine, preoperative systematic treatment may reshape the clinical outcomes of advanced intrahepatic cholangiocarcinoma patients. We describe the case of a 38-year-old female who has been diagnosed with stage IV intrahepatic cholangiocarcinoma with a high tumor mutational burden and positively programmed death-ligand 1 (PD-L1) expression. The patient was treated with programmed cell death 1 (PD-1) inhibitors combined with tyrosine kinase inhibitors (TKIs). After 7 cycles of combination therapy, she underwent radical resection and no tumor cells were found in the postoperative histopathological examination. In addition, the patient’s survival time had reached 25 months, as of August 2021. To date, this is the first case of successful radical resection after combined immunotherapy with TKIs for advanced PD-L1-positive intrahepatic cholangiocarcinoma with a high tumor mutational burden (TMB). The case provides a new approach to the treatment of advanced intrahepatic cholangiocarcinoma.

scholarly journals Integration of Stereotactic Body Radiation Therapy With Tyrosine Kinase Inhibitors in Stage IV Oncogene‐Driven Lung Cancer

2016 ◽  
Vol 21 (8) ◽  
pp. 964-973 ◽  
Author(s):  
Meghan Campo ◽  
Hani Al‐Halabi ◽  
Melin Khandekar ◽  
Alice T. Shaw ◽  
Lecia V. Sequist ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Radiation Therapy ◽  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Stereotactic Body Radiation Therapy ◽  
Stage Iv ◽  
Stereotactic Body Radiation

scholarly journals Neuromuscular Complications of Targeted Anticancer Agents: Can Tyrosine Kinase Inhibitors Induce Myasthenia Gravis? Getting Answers From a Case Report up to a Systematic Review

2021 ◽  
Vol 11 ◽  
Author(s):  
Dimitrios C. Ziogas ◽  
Dimitrios Mandellos ◽  
Charalampos Theocharopoulos ◽  
Panagiotis-Petros Lialios ◽  
Spyros Bouros ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Myasthenia Gravis ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Series ◽  
Braf Inhibitor ◽  
First Case ◽  
Long Term Treatment ◽  
Neuromuscular Complications

More than 40 tyrosine kinase inhibitors (TKIs) have received hematological or oncological indications over the past 20 years, following the approval of imatinib, and many others are currently being tested in clinical and preclinical level. Beyond their common toxicities, no certain agent from this large class of molecularly targeted therapies was strongly associated with “off-target” impairment of neuromuscular transmission, and although myasthenia gravis (MG) is a well-characterized autoimmune disorder, only few sporadic events proven by serologically detected causative autoantibodies and/or by positive electrophysiological tests are reported in the literature. Herein, we present the first case of anti-MUSK (+) MG in a woman with metastatic BRAF-mutant melanoma after long-term treatment with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor). Triggered by this report, a systematic literature review was conducted, summarizing all other cancer cases that developed MG, after exposure to any type of targeted agent and regardless of the underlying malignancy. All available data on the clinical diagnosis, the potential of administered TKIs to induce a seropositive myasthenic syndrome, the immune and non-immune-mediated pathogenesis of postsynaptic damage, and the challenging management of this neuromuscular toxicity were collected and discussed. In the presented case, MG was confirmed by both autoantibodies and nerve-conduction tests, while its reactivation after TKIs rechallenge supports a more than coincidental association. The following review identified 12 cancer cases with TKI-related MG in six case reports and one case series. In most of them, the myasthenia diagnosis was challenging, since the clinical symptomatology of fatigable weakness was not corroborating with consistent laboratory and electrophysiological findings. In fact, anti-AchR titers were positive in five and anti-MuSK only in the abovementioned individual. The symptomatology corresponded to TKI discontinuation and standard treatment with pyridostigmine and prednisolone; intravenous immunoglobulin was added only in three, and two required mechanical ventilation. In an era where TKIs will be prescribed more frequently for various malignancies, even in combinations with immune-checkpoint inhibitors, this report synthesizes their risk for neuromuscular complications and increases the clinicians’ awareness in order to extend the on-treatment and overall survival of TKI-treated cancer patients.

Equity in access to tyrosine kinase inhibitors among veterans diagnosed with renal cell carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18051-e18051
Author(s):  
Julie Ann Lynch ◽  
Kristine E. Lynch ◽  
Kelly Kristin Filipski ◽  
Brygida Berse ◽  
Donna Rivera ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Tyrosine Kinase ◽  
Cell Carcinoma ◽  
Tyrosine Kinase Inhibitors ◽  
Renal Cell ◽  
Kinase Inhibitors ◽  
Stage Iv ◽  
Clinical Information ◽  
Chi Square ◽  
Access To Treatment

e18051 Background: Tyrosine kinase inhibitors (TKIs) have dramatically improved outcomes of advanced renal cell carcinoma (RCC) patients, although complete remission is uncommon. Disease-specific survival in RCC varies by race/ethnicity, but race is not an independent predictor of survival within single-payer healthcare systems, pointing to the importance of access to treatment. We analyzed patient-level utilization of three TKIs (sunitinib, sorafenib, and pazopanib) among veterans with RCC. Methods: In this retrospective cohort study, we used data from Department of Veterans Affairs (VA) Corporate Data Warehouse to identify veterans diagnosed with RCC from 2006 to 2015 and exposed to TKIs, and to obtain their demographic and clinical information. The distribution of patients’ characteristics across treatments was evaluated using chi square and t-tests. Results: Of 2,410 patients exposed to TKIs, 956 (40%) received more than one TKI. Sunitinib was prescribed to 1,761 (73%) patients, pazopanib to 766 (32%), and sorafenib to 600 (25%) patients. The use of sorafenib declined steadily over time, from 37% of patients diagnosed in 2006 to 2% of those diagnosed in 2015, while the use of pazopanib grew from 8% to 38%, respectively. The comparison group were unexposed patients in Stage IV RCC (N = 1,144). Patients exposed to targeted treatments were significantly younger at diagnosis than those with no exposure (mean [M] age 65 years, SD 9 vs. m = 70 years, SD 10; p < 001). There were no statistically significant racial/ethnic or gender differences between patients exposed and unexposed to TKIs. Exposed patients had significantly higher body mass index (BMI) than unexposed (M = 29.6, SD 6 vs m = 27.9, SD 6, respectively; p < 0.01). Receipt of TKI was positively correlated with both surgery and chemotherapy, and negatively correlated with Charlson comorbidity index (p < 0.01). Conclusions: We documented equal access to TKIs treatment within the VA among RCC patients of different ethnic backgrounds and gender. Treatment with TKIs was correlated with younger age and fewer comorbidities, but higher BMI. We observed trends in use of individual TKIs, with more recently approved pazopanib gradually replacing sorafenib and sunitinib.

scholarly journals Tyrosine kinase inhibitors and modifications of thyroid function tests: a review

2009 ◽  
Vol 160 (3) ◽  
pp. 331-336 ◽  
Author(s):  
Frédéric Illouz ◽  
Sandrine Laboureau-Soares ◽  
Séverine Dubois ◽  
Vincent Rohmer ◽  
Patrice Rodien
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Thyroid Function ◽  
Tyrosine Kinases ◽  
Kinase Inhibitors ◽  
Thyroid Function Tests ◽  
Hormone Regulation ◽  
Clinical Observations ◽  
Function Tests ◽  
First Case

Tyrosine kinase inhibitors (TKI) belong to new molecular multi-targeted therapies that are approved for the treatment of haematological and solid tumours. They interact with a large variety of protein tyrosine kinases involved in oncogenesis. In 2005, the first case of hypothyroidism was described and since then, some data have been published and have confirmed that TKI can affect the thyroid function tests (TFT). This review analyses the present clinical and fundamental findings about the effects of TKI on the thyroid function. Various hypotheses have been proposed to explain the effect of TKI on the thyroid function but those are mainly based on clinical observations. Moreover, it appears that TKI could alter the thyroid hormone regulation by mechanisms that are specific to each molecule. The present propositions for the management of TKI-induced hypothyroidism suggest that we assess the TFT of the patients regularly before and during the treatment by TKI. Thus, a better approach of patients with TKI-induced hypothyroidism could improve their quality of life.

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