The treatment of immune thrombocytopenia (ITP) in adults has evolved rapidly over the past decade. The second-generation thrombopoietin receptor agonists (TPO-RAs), romiplostim, eltrombopag, and ...avatrombopag are approved for the treatment of chronic ITP in adults. However, their use in pregnancy is labeled as category C by the United States Food and Drug Administration (FDA) due to the lack of clinical data on human subjects. ITP is a common cause of thrombocytopenia in the first and second trimester of pregnancy, which not only affects the mother but can also lead to thrombocytopenia in the neonatal thrombocytopenia secondary to maternal immune thrombocytopenia (NMITP). Corticosteroids, intravenous immunoglobulins (IVIGs) are commonly used for treating acute ITP in pregnant patients. Drugs such as rituximab, anti-D, and azathioprine that are used to treat ITP in adults, are labeled category C and seldom used in pregnant patients. Cytotoxic chemotherapy (vincristine, cyclophosphamide), danazol, and mycophenolate are contraindicated in pregnant women. In such a scenario, TPO-RAs present an attractive option to treat ITP in pregnant patients. Current evidence on the use of TPO-RAs in pregnant women with ITP is limited. In this narrative review, we will examine the preclinical and the clinical literature regarding the use of TPO-RAs in the management of ITP in pregnancy and their effect on neonates with NMITP.
Opinion statement
Desmoid tumors are rare tumors with a tendency to infiltrate locally. The lack of a standard treatment approach makes choosing the most appropriate treatment for patients ...challenging. Most experts recommend watchful observation for asymptomatic patients as spontaneous regression of tumor is observed in up to 20% of patients. Upfront resection of the desmoid tumor has fallen out of favor due to high morbidity and high relapse rates associated with the tumor. Systemic therapy has evolved over several decades. Where chemotherapy, hormonal therapy, and non-steroidal anti-inflammatory drugs were used over the last several decades, tyrosine kinase inhibitors came to the forefront within the last decade. Most recently, gamma-secretase inhibitors have shown significant clinical benefit in patients with desmoid tumors, bringing forth an entirely new mechanistic approach. Several Wnt pathway inhibitors are also under development. Invasive approaches like cryoablation have also shown clinical benefit in patients with extra-abdominal desmoid tumors in recent years. The recent approval of nirogacestat has ushered in a new era of treatment for patients diagnosed with desmoid tumors. Several new molecules are expected to be approved over the coming years.
A primary cardiac angiosarcoma is a rare type of soft-tissue sarcoma with a high mortality rate. This report describes a young woman who presented with chest pain and worsening shortness of breath ...over the course of a year. She was diagnosed with and treated for latent tuberculosis and autoimmune pericarditis over the last year, however, her condition kept worsening. Further workup revealed a large pericardial and right atrial mass associated with multiple lung nodules. The biopsy from the lung mass showed angiosarcoma, and she was diagnosed with primary metastatic angiosarcoma of the pericardium. She was treated with doxorubicin and Ifosfamide (AIM-75 regimen), which led to a partial response. However, soon after completion of six cycles, the tumour progressed rapidly, leading to cardio-respiratory failure. In this report, we will discuss the clinical challenges and treatment options (surgical and medical) that are available for treating patients with angiosarcoma of the heart.
Background: To determine the risk of mortality and factors associated with survival amongst patients diagnosed with primary hepatic angiosarcoma (PHA). Methods: All patients diagnosed with ...hepatocellular carcinoma (HCC) or PHA from 2004 to 2014 were identified from the National Cancer Database (NCDB). Further analysis was performed within the cohort of patients with PHA to assess the impact of surgery, chemotherapy, radiation, and facility type on overall survival (OS). A multivariable analysis using the Cox proportional methods and a survival analysis using the Kaplan−Meier method were used. Results: A total of 117,633 patients with HCC were identified, out of whom 346 patients had PHA. Patients with PHA had a mean age of 62.9 years (SD 13.7), the majority were men (64.7%), white (85.8%), and had a Charlson comorbidity index (CCI) of zero (66.2%). A third of the patients with PHA (35.7%) received chemotherapy, and 14.6% underwent a surgical resection. The median survival was 1.9 months (1.8−2.4 months) compared to patients with HCC (10.4 months, 10.2−10.5) (aHR-2.41, 95% CI: 2.10−2.77, p < 0.0001). Surgical resection was associated with a higher median survival (7.7 versus 1.8 months, aHR-0.23, 95% CI: 0.15−0.37, p < 0.0001). A receipt of chemotherapy was associated with a higher median survival than no chemotherapy (5.1 versus 1.2 months, aHR-0.44, 95% CI: 0.32−0.60, p < 0.0001), although the survival benefit did not persist long term. Conclusion: PHA is associated with poor outcomes. A surgical resection and chemotherapy are associated with improved survival outcomes; however, the long-term benefits of chemotherapy are limited.
Background: Several drugs and treatment modalities are under investigation to improve current melanoma therapy options. This review profiles the trends in clinical trial investment in late-stage ...melanoma, and anticipates what changes are expected in melanoma treatment, with a focus on exploratory drug mechanisms. Methods: We reviewed nine international clinical trial databases for registered, interventional, and phase 3 cutaneous melanoma clinical trials since 2010. Results: 73 trials studied drug therapies in late-stage (stage III and IV) melanoma. Exploratory mechanisms were investigated in 32% (23/73) of the late-stage melanoma drug therapy trials. Most exploratory drug trials include immunotherapy drug mechanisms (15/23 trials). Two exploratory mechanisms showed promise: the anti-LAG3 antibody, relatlimab, and the hapten modified vaccine, MVax. Many (52%) trials of exploratory mechanisms are ongoing including the use of adoptive cell transfer immunotherapies, dendritic cell vaccine therapy, and histone deacetylase (HDAC) inhibitors, among others. Conclusions: Since most clinical trials focus on previously approved drug mechanisms, it is likely that paradigm-changing treatments will involve these therapies being used in new treatment contexts or combinations. Only 2 exploratory drug mechanisms studied since 2010 have achieved promising results in the phase 3 setting, though many other trials are ongoing at this time.
Cardiac angiosarcoma is a rare malignancy with an aggressive course and poor prognosis. We present a 26‐year old man who came to our clinic with shortness of breath and was diagnosed with a ...right‐sided atrial mass. He underwent urgent resection of the mass. The pathology confirmed the mass to be cardiac angiosarcoma with positive microscopic margins (R1 resection). Since reresection was not feasible, the patient started treatment with concurrent paclitaxel (80 mg/m2 weekly) and proton beam therapy (61 Cobalt equivalent delivered over five weeks). After completing the concurrent chemotherapy and radiation therapy, he was treated with adjuvant chemotherapy using gemcitabine (900 mg/m2 on Days 1 and 8) and docetaxel (100 mg/m2 on Day 8) every three weeks. After three cycles, the patient developed severe dermatitis, and hence further chemotherapy was withheld. The patient is alive at 26 months since receiving his surgery and 18 months since the completion of treatment. Patients with cardiac angiosarcoma who undergo R1 resection have a median survival of six months. More radical approaches such as orthotopic heart‐lung transplant or prolonged durations of chemotherapy lead to minimal improvement in survival at the cost of increased morbidity. Here, we describe a novel approach to a rare disease that resulted in prolonged survival and led to a better quality of life without any long‐term morbidity to the patient.
Cardiac angiosarcoma is a rare tumor of the heart associated with a poor prognosis. Patients who undergo R1 resection have a median survival of six months. Multiple efforts to improve the outcome have resulted in severe morbidity and mortality, without increasing survival. Here, we report a novel approach of concurrent chemotherapy and proton beam therapy followed by adjuvant chemotherapy that resulted in continued survival beyond two years without any recurrence or any toxicity to the heart.
BackgroundImmune checkpoint inhibitors (ICI) and targeted therapies (TT) have improved the survival outcomes in patients with advanced melanoma. However, less is known about their impact on Asian ...patients with melanoma. In this study, we hypothesize that patients of Asian ancestry would have improved survival for advanced melanoma since the introduction of ICI and TT in 2011.MethodsAsian patients with melanoma were identified in the National Cancer Database (NCDB) from 2004–2016. Patient, tumor, and treatment characteristics were compared for populations treated before and after 2011 using Chi-square analyses. Overall survival (OS) was analyzed using Kaplan-Meier estimates.Results1,411 Asian patients with melanoma were identified. Overall, 21% were melanoma in situ, and 79% were invasive melanomas. 62% of patients did not have a documented histologic subtype. The most common reported histologies were superficial spreading (14%) and acral lentiginous (10%) melanomas. Primary locations included 41% lower extremity, 17% upper extremity, and 11% head and neck. The age at diagnosis has increased during the study period - 38% over 60 years old in 2004, to 54% in 2016 (P<0.002). Kaplan-Meier survival estimates were performed for the whole Asian melanoma population and showed worse OS for all patients diagnosed after 2011 compared with patients diagnosed before 2011 - 83% vs 84% at 24 months (P=0.0033), 71% vs 76% at 48 months (P<0.001), respectively. However, the OS for those stage IV melanomas diagnosed after 2011 is better compared to patients diagnosed before 2011 - 52% vs. 26% at 24 months (P<0.001), and 20% vs. 13% at 48 months (P<0.001), respectively. (table 1) The worse OS trend seen for all patients was driven by those with early stage disease and likely does not reflect melanoma specific survival. Utilization rates of ICI and TT in Stage IV melanoma in Asian populations was significantly higher after 2011 (9% versus 30% before and after 2011 respectively, p=0.026). This was comparable to the utilization rates of 12% vs 34% for all patients (all races) with stage IV melanomas captured in the NCDB for the periods from 2004–2011 and 2012–2016.Abstract 729 Table 1Survival for stage IV asian melanoma*Longest follow up time in group 2 (Asian Melanoma diagnosed 2012 and after)ConclusionsAsian patients with melanoma are receiving diagnoses at older ages. Despite decreases in OS for all Asian patients with melanoma, advanced stage IV of the diseases have improved outcomes for the group treated in the era of ICI and TT. Further investigation is warranted to understand the treatment, patient, and tumor characteristics that predict response in this demographic of patients.
Background
This study analyzes the pattern of use of single agent anticancer therapy (SAACT) in the treatment and survival of advanced hepatocellular carcinoma (aHCC) before and after sorafenib was ...FDA approved in 2007.
Methods
Adult patients diagnosed with HCC and treated with only ACT from 2004 – 2014 were identified in NCDB database. Patients were analyzed during three time frames: 2004–2006 (pre‐sorafenib (PS)), 2007–2010 (early sorafenib (ES)) and 2011–2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan‐Meier method were used for analyses.
Results
The NCDB contained 31,107 patients with HCC diagnosed from 2004–2014 and treated with ACT alone. Patients were generally men (78.0%), >50 years of age (92.5%). A significant increase in the rate of adaption of SAACT was observed over time: 6.2% PS, 15.2% ES, and 22.2% LS (p < 0.0001). During this later period, the highest proportion of SAACT is among academic and integrated network facilities (23.3%) as compared to community facilities (17.0%, p < 0.0001). The median overall survival of patients with aHCC treated only with SAACT improved significantly over time from 8.0 months (m) (95% CI: 7.4–8.8) to 10.7 m (10.4–11.2) to 15.6 m (15.2–16.0, p < 0.001). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.28, (5% CI: 1.23–1.32), patients without insurance (HR 1.11, 1.06–1.16) and estimated household income of <$63,000 (HR 1.09, 1.05–1.13).
Conclusion
aHCC patients treated only with ACT have experienced an overall improvement in survival, but significant differences exist between facility type, insurance status, and income.
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