TSH-secreting pituitary adenoma: late diagnosis and effectiveness of therapy

The modern therapeutic and diagnostic algorithms allow timely detection of pituitary disorder to prescribe adequate treatment. Meanwhile, when interpreting the thyroid status, physicians need to take into account the extremely rare but the actually existing possibility of central thyrotoxicosis. The worldwide practice shows that diagnosis of this condition is rather challenging. We report a clinical case of a TSH-secreting pituitary adenoma in a 47-year-old female who received a long-term thyrostatic therapy for thyrotoxicosis. The patient was diagnosed with Graves’ disease; however, thyrotoxicosis was actually caused by TSH-oma. The key laboratory signs of central thyrotoxicosis included the combination of episodes of normal or elevated TSH level with the high or normal free T4 level. MRI showed a pituitary macroadenoma. The clinical manifestations of thyrotoxicosis made it possible to rule out the thyroid hormone resistance syndrome. The attempted therapy with octreotide eliminated the clinical and laboratory signs of thyrotoxicosis, so the conservative method was selected as first-line therapy. The features of clinical and laboratory signs, as well as the principles of differential diagnosis and modern methods for treating TSH-secreting pituitary adenomas are discussed.

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Long-Term Sustained Disease Control With Immunotherapy in Chemotherapy-Refractory Merkel Cell Carcinoma

healthbook TIMES Oncology Hematology ◽

10.36000/hbt.oh.2019.01.003 ◽

2019 ◽

pp. 8-11

Author(s):

Deborah Yihler ◽

Kathrin Vollmer ◽

Antonio Cozzio

Keyword(s):

Cell Carcinoma ◽

Merkel Cell Carcinoma ◽

Inadequate Response ◽

Merkel Cell ◽

First Line ◽

Treatment Protocols ◽

First Line Therapy ◽

Significant Toxicity ◽

Clinical Responses

ABSTRACT Merkel cell carcinoma (MCC) is a rare and difficult-to-treat cutaneous malignancy with a poor prognosis. Treatment protocols for localized MCC are well established. Until recently, metastatic MCC has generally been treated with chemotherapy, which was often associated with poor clinical responses and significant toxicity. In this report, the case of a patient with metastatic MCC who received avelumab, an immune checkpoint inhibitor, after an inadequate response to first-line radiotherapy and chemotherapy, is presented. Nine months after the initiation of the treatment with avelumab, the patient achieved a partial remission with no treatment-related adverse events. After a follow-up of 17 months, a systematically ongoing partial response was reported. In conclusion, this case study offers a clinical insight into the patient’s case and highlights the importance of immunotherapy as a first-line therapy for metastatic MCC.

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First-Line Atezolizumab Plus Bevacizumab versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Cancers ◽

10.3390/cancers13050931 ◽

2021 ◽

Vol 13 (5) ◽

pp. 931

Author(s):

Chi-Leung Chiang ◽

Sik-Kwan Chan ◽

Shing-Fung Lee ◽

Horace Cheuk-Wai Choi

Keyword(s):

Hepatocellular Carcinoma ◽

Cost Effectiveness ◽

Lifetime Cost ◽

Cost Effective ◽

First Line ◽

First Line Therapy ◽

Payer Perspective ◽

Life Years ◽

Using Data

Background: The IMbrave 150 trial revealed that atezolizumab plus bevacizumab (atezo–bev) improves survival in patients with unresectable hepatocellular carcinoma (HCC) (1 year survival rate: 67.2% vs. 54.6%). We assessed the cost-effectiveness of atezo–bev vs. sorafenib as first-line therapy in patients with unresectable HCC from the US payer perspective. Methods: Using data from the IMbrave 150, we developed a Markov model to compare the lifetime cost and efficacy of atezo–bev as first-line systemic therapy in HCC with those of sorafenib. The main outcomes were life-years, quality-adjusted life-years (QALYs), lifetime costs, and incremental cost-effectiveness ratio (ICER). Results: Atezo–bev demonstrated a gain of 0.44 QALYs, with an additional cost of USD 79,074. The ICER of atezo–bev was USD 179,729 per QALY when compared with sorafenib. The model was most sensitive to the overall survival hazard ratio and body weight. If we assumed that all patients at the end of the IMbrave 150 trial were cured of HCC, atezo–bev was cost-effective (ICER USD 53,854 per QALY). However, if all patients followed the Surveillance, Epidemiology, and End Results data, the ICER of atezo–bev was USD 385,857 per QALY. Reducing the price of atezo–bev by 20% and 29% would satisfy the USD 150,000/QALY and 100,000/QALY willingness-to-pay threshold. Moreover, capping the duration of therapy to ≤12 months or reducing the dosage of bev to ≤10 mg/kg would render atezo–bev cost-effective. Conclusions: The long-term effectiveness of atezo–bev is a critical but uncertain determinant of its cost-effectiveness. Price reduction would favorably influence cost-effectiveness, even if long-term clinical outcomes were modest. Further studies to optimize the duration and dosage of therapy are warranted.

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Not BCL2 mutation but dominant mutation conversation contributed to acquired venetoclax resistance in acute myeloid leukemia

Biomarker Research ◽

10.1186/s40364-021-00288-7 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Xiang Zhang ◽

Jiejing Qian ◽

Huafeng Wang ◽

Yungui Wang ◽

Yi Zhang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Underlying Mechanism ◽

Lymphocytic Leukemia ◽

First Line ◽

Dominant Mutation ◽

First Line Therapy ◽

Line Therapy ◽

Acute Myeloid

AbstractVenetoclax (VEN) plus azacitidine has become the first-line therapy for elderly patients with acute myeloid leukemia (AML), and has a complete remission (CR) plus CR with incomplete recovery of hemogram rate of ≥70%. However, the 3-year survival rate of these patients is < 40% due to relapse caused by acquired VEN resistance, and this remains the greatest obstacle for the maintenance of long-term remission in VEN-sensitive patients. The underlying mechanism of acquired VEN resistance in AML remains largely unknown. Therefore, in the current study, nine AML patients with acquired VEN resistance were retrospectively analyzed. Our results showed that the known VEN resistance-associated BCL2 mutation was not present in our cohort, indicating that, in contrast to chronic lymphocytic leukemia, this BCL2 mutation is dispensable for acquired VEN resistance in AML. Instead, we found that reconstructed existing mutations, especially dominant mutation conversion (e.g., expanded FLT3-ITD), rather than newly emerged mutations (e.g., TP53 mutation), mainly contributed to VEN resistance in AML. According to our results, the combination of precise mutational monitoring and advanced interventions with targeted therapy or chemotherapy are potential strategies to prevent and even overcome acquired VEN resistance in AML.

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Long‐term outcome comparing histological grades of follicular lymphoma patients treated with immunochemotherapy as first‐line therapy: A retrospective analysis from two institutions

European Journal Of Haematology ◽

10.1111/ejh.13359 ◽

2019 ◽

Vol 104 (3) ◽

pp. 198-206

Author(s):

Santiago Mercadal ◽

Juan‐Manuel Sancho ◽

Fina Climent ◽

Gustavo Tapia ◽

Helena Pomares ◽

...

Keyword(s):

Follicular Lymphoma ◽

Retrospective Analysis ◽

First Line ◽

Term Outcome ◽

Long Term Outcome ◽

First Line Therapy ◽

Line Therapy

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Diagnosis and Multimodality Management of Cushing’s Disease: A Practical Review

International Journal of Endocrinology ◽

10.1155/2013/893781 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 10

Author(s):

Gabriel Zada

Keyword(s):

Pituitary Adenoma ◽

Cushing’S Disease ◽

Patient Survival ◽

Clinical Laboratory ◽

Management Strategies ◽

Serum Cortisol ◽

Cushing's Disease ◽

First Line ◽

Stepwise Approach

Cushing’s Disease is caused by oversecretion of ACTH from a pituitary adenoma and results in subsequent elevations of systemic cortisol, ultimately contributing to reduced patient survival. The diagnosis of Cushing’s Disease frequently involves a stepwise approach including clinical, laboratory, neuroimaging, and sometimes interventional radiology techniques, often mandating multidisciplinary collaboration from numerous specialty practitioners. Pituitary microadenomas that do not appear on designated pituitary MRI or dynamic contrast protocols may pose a particularly challenging subset of this disease. The treatment of Cushing’s Disease typically involves transsphenoidal surgical resection of the pituitary adenoma as a first-line option, yet may require the addition of adjunctive measures such as stereotactic radiosurgery or medical management to achieve normalization of serum cortisol levels. Vigilant long-term serial endocrine monitoring of patients is imperative in order to detect any recurrence that may occur, even years following initial remission. In this paper, a stepwise approach to the diagnosis, and various management strategies and associated outcomes in patients with Cushing’s Disease are discussed.

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Cost-Effectiveness of Pembrolizumab Plus Chemotherapy Versus Pembrolizumab Monotherapy in Metastatic Non-Squamous and Squamous NSCLC Patients With PD-L1 Expression ≥ 50%

Frontiers in Pharmacology ◽

10.3389/fphar.2021.803626 ◽

2022 ◽

Vol 12 ◽

Author(s):

Qiao Liu ◽

Zhen Zhou ◽

Xia Luo ◽

Lidan Yi ◽

Liubao Peng ◽

...

Keyword(s):

Cost Effectiveness ◽

Life Expectancy ◽

Cost Effective ◽

Base Case ◽

First Line ◽

Term Survival ◽

First Line Therapy ◽

Line Therapy ◽

Nsclc Patients

Objective To compare the cost-effectiveness of the combination of pembrolizumab and chemotherapy (Pembro+Chemo) versus pembrolizumab monotherapy (Pembro) as the first-line treatment for metastatic non-squamous and squamous non-small-cell lung cancer (NSCLC) with PD-L1expression ≥50%, respectively, from a US health care perspective.Material and Methods A comprehensive Makrov model were designed to compare the health costs and outcomes associated with first-line Pembro+Chemo and first-line Pembro over a 20-years time horizon. Health states consisted of three main states: progression-free survival (PFS), progressive disease (PD) and death, among which the PFS health state was divided into two substates: PFS while receiving first-line therapy and PFS with discontinued first-line therapy. Two scenario analyses were performed to explore satisfactory long-term survival modeling.Results In base case analysis, for non-squamous NSCLC patients, Pembro+Chemo was associated with a significantly longer life expectancy [3.24 vs 2.16 quality-adjusted life-years (QALYs)] and a substantially greater healthcare cost ($341,237 vs $159,055) compared with Pembro, resulting in an ICER of $169,335/QALY; for squamous NSCLC patients, Pembro+Chemo was associated with a slightly extended life expectancy of 0.22 QALYs and a marginal incremental cost of $3,449 compared with Pembro, resulting in an ICER of $15,613/QALY. Our results were particularly sensitive to parameters that determine QALYs. The first scenario analysis yielded lower ICERs than our base case results. The second scenario analysis founded Pembro+Chemo was dominated by Pembro.Conclusion For metastatic non-squamous NSCLC patients with PD-L1 expression ≥50%, first-line Pembro+Chemo was not cost-effective when compared with first-line Pembro. In contrast, for the squamous NSCLC patient population, our results supported the first-line Pembro+Chemo as a cost-effective treatment. Although there are multiple approaches that are used for extrapolating long-term survival, the optimal method has yet to be determined.

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Optimized first-line therapy for stage IV breast cancer brings long-term disease-free survival: a case report and biological analysis

Translational Breast Cancer Research ◽

10.21037/tbcr.2020.04.01 ◽

2020 ◽

Vol 1 ◽

pp. 7-7

Author(s):

Li Bian ◽

Fengrui Xu ◽

Tao Wang ◽

Huiqiang Zhang ◽

Yang Cao ◽

...

Keyword(s):

Breast Cancer ◽

Disease Free Survival ◽

Stage Iv ◽

First Line ◽

Free Survival ◽

First Line Therapy ◽

Line Therapy ◽

Stage Iv Breast Cancer ◽

Disease Free

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Development of atrial fibrillation catheter ablation and ablation strategies

ESC CardioMed ◽

10.1093/med/9780198784906.003.0509 ◽

2018 ◽

pp. 2168-2173

Author(s):

Gerhard Hindricks ◽

Nikolaos Dagres ◽

Philipp Sommer ◽

Andreas Bollmann

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Antiarrhythmic Drug ◽

Left Ventricular ◽

Left Ventricular Ejection ◽

First Line ◽

Ventricular Ejection Fraction ◽

First Line Therapy

Catheter ablation has evolved to an established therapy for patients with symptomatic atrial fibrillation (AF). Complete pulmonary vein isolation currently is the best endpoint for catheter ablation. This can be achieved with balloon-based cryoablation as well as by point-by-point radiofrequency ablation supported by non-fluoroscopic mapping technologies—both technologies seem equally effective. AF catheter ablation is indicated in patients with symptomatic AF usually after failure of antiarrhythmic drug therapy. Selected patients with AF and tachycardia-induced heart failure may benefit from ablation by a significant improvement of left ventricular ejection fraction. The success rate (i.e. freedom from AF and atrial tachycardia) after a single procedure is approximately 50–60% for patients with paroxysmal AF and 40% for patients with persistent AF. With multiple procedures, freedom from AF can be achieved in up to 80% of patients with paroxysmal AF and 60% of patients with persistent AF. When performed after failed rhythm control attempts with antiarrhythmic drugs, catheter ablation is superior to a further attempt with antiarrhythmic drug medication. When applied as first-line therapy, catheter ablation tends to be slightly superior to first-line antiarrhythmic drug treatment. The complication rate of AF catheter ablation is 5–7%; severe complications occur in 2–3% (cardiac tamponade, periprocedural stroke, atrio-oesophageal fistula). Catheter ablation significantly improves quality of life but has no proven effect on mortality and/or stroke. Thus, in general, oral anticoagulation should be continued long term even if ablation is considered successful.

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