Home treatment of patients with cancer-associated venous thromboembolism - An evaluation of daily practice.

BACKGROUND: Home treatment of cancer-associated venous thromboembolism (VTE) is challenging due to the high risk of adverse events. While home treatment is quite agreeable to cancer patients, studies evaluating the safety of VTE home treatment in this setting are largely unavailable. METHODS: This was an observational study in patients with cancer-associated VTE. The main outcomes were the proportion of patients treated at home (hospital discharge <24 h after diagnosis) and the 3-month incidence of VTE-related adverse events (major bleeding, recurrent VTE and/or suspected VTE-related mortality) in patients managed in hospital versus at home. RESULTS: A total of 183 outpatients were diagnosed with cancer-associated VTE: 69 had deep vein thrombosis (DVT) and 114 had pulmonary embolism (PE ±â€¯DVT). Of those, 120 (66%) were treated at home; this was 83% for patients with DVT and 55% for patients with PE (±DVT). The 3-month incidence of any VTE-related adverse event was 13% in those treated at home versus 19% in the hospitalized patients (HR 0.48; 95%CI 0.22-1.1), independent of initial presentation as PE or DVT. All-cause 3-month mortality occurred in 33 patients treated as inpatient (54%) compared to 29 patients treated at home (24%; crude HR 3.1 95%CI 1.9-5.0). CONCLUSIONS: Two-third of patients with cancer-associated VTE - including PE - were selected to start anticoagulant treatment at home. Cancer-associated VTE is associated with high rates of VTE-related adverse events independent of initial in hospital or home treatment. However, home treatment may be a good option for selected patients with cancer-associated DVT or PE.

Atrial fibrillation and cancer - An unexplored field in cardiovascular oncology.

An increasing body of evidence suggests an association between cancer and atrial fibrillation (AF). The exact magnitude and underlying mechanism of this association are however unclear. Cancer-related inflammation, anti-cancer treatment and other cancer-related comorbidities are proposed to affect atrial remodelling, increasing the susceptibility of cancer patients for developing AF. Moreover, cancer is assumed to modify the risk of thromboembolisms and bleeding. A thorough and adequate understanding of these risks is however lacking, as current literature is scarce and show ambiguous results in AF patients. The standardized risk-models that normally aid the clinician in the decision of initiating anticoagulant therapy do not take the presence of malignancy into account. Other factors that complicate risk assessment in AF patients with cancer include drug-drug interactions and other cancer-related comorbidities such as renal impairment. In this review, we highlight the available literature regarding epidemiological association, risk assessment and anticoagulation therapy in AF patients with cancer.

Incidence and demographics of giant cell tumor of bone in The Netherlands: First nationwide Pathology Registry Study.

Background and purpose - Giant cell tumors of bone (GCT-B) are rare, locally aggressive tumors characterized by an abundance of giant cells. Incidence studies for GCT-B are rare. This is the first study using a fully automated 100% covering pathology database, the nationwide Dutch Pathology Registry (17 million inhabitants), PALGA, to calculate incidence rates for GCT-B. Patients and methods - From PALGA, all pathology excerpts were retrieved for patients diagnosed with GCT-B, giant cell tumors of tenosynovium, and giant cell tumors of soft tissue between January 1, 2009 and December 31, 2013. The incidence of GCT-B was calculated. Results - In total, 8,156 excerpts of 5,922 patients were retrieved; these included 138 first GCT-B diagnosis. For GCT-B the incidence was 1.7 per million inhabitants per year with a male to female ratio of 1:1.38 and a median age of 35 years (9-77). Most common localization was the femur (35%), followed by the tibia (18%). No differences in localization according to age and sex were found. The incidence rate of local recurrence was 0.40 per million inhabitants per year. Interpretation - This is the first nationwide study reporting the incidence of GCT-B, based on a nationwide pathology database with 100% coverage of pathology departments. Current incidence calculations are based only on doctor-driven registries. We confirmed that GCT-B is a rare disease with an incidence that is slightly higher than previously published. The relatively young median age of patients and the high incidence of recurrence stresses the importance of developing more effective treatments for this disease.

Outcome of Nonsurgical Management of Extra-Abdominal, Trunk, and Abdominal Wall Desmoid-Type Fibromatosis: A Population-Based Study in the Netherlands.

INTRODUCTION: Nonsurgical management of patients with desmoid-type fibromatosis (DF) is increasing. This study tries to provide insight on type, usage, and outcome of first-line nonsurgical management strategies. PATIENTS AND METHODS: From the Dutch Pathology Registry (PALGA), patients with extra-abdominal or trunk/abdominal wall DF, diagnosed between 1993 and 2013, were identified. First-line treatment was analyzed. Best response (BR) using RECIST criteria from start of treatment/surveillance until change of treatment or last follow-up was analyzed. RESULTS: Ninety-one of the 1141 identified patients had first-line nonsurgical management. The percentage of patients treated nonsurgically increased from 0.6% in 1993-1998 to 12.8% in 2009-2013. Thirty-seven patients had surveillance (41%), 35 radiotherapy (38%), and 19 systemic treatment (21%). BR for surveillance was complete response (CR) in 2/37, partial response (PR) in 4/37, stable disease (SD) in 21/37, progressive disease (PD) in 5/37, and unknown in 5/37 patients. BR for radiotherapy was CR in 4/35, PR in 11/35, SD in 16/35, and unknown in 4/35. BR for systemic treatment was CR in 1/19, PR in 1/19, SD in 10/19, PD in 2/19, and unknown in 5/19. Totally, 91% of patients did not progress. DISCUSSION: Given the low percentage (9%) of PD of nonsurgical management, these data can be used in shared decision making with the patient regarding optimal treatment.

The incidence, mutational status, risk classification and referral pattern of gastro-intestinal stromal tumours in the Netherlands: a nationwide pathology registry (PALGA) study.

Symptomatic gastrointestinal stromal tumours (GIST) are infrequent with an incidence of 12.7 per million inhabitants in the western population. We studied whether the incidence of GIST has further increased between 2003 and 2012 and assessed the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. From PALGA, the nationwide Dutch Pathology Registry, pathology excerpts from all patients with a GIST or GIST-like tumour between 2003 and 2012 were retrieved to calculate incidence rates. Full pathology reports were retrieved of resections in 2011 and 2012 to study the frequency of mutations, risk groups, histological subtypes and immunohistochemistry results. The incidence of GIST increased to 17.7 per million inhabitants in 2012 with a median age of 67 years. Mutational analysis was performed in 33.9% of patients with a resection between 2011 and 2012 (KIT mutation 67.5%, PDGFRA 16.3%, wild-type 11.4%). The percentage of high risk patients in the different risk classifications varied from 19.9% to 38.0% depending on the used classification. Only 35.9% of patients had diagnosis or revision of pathology diagnosis within three months in a designated GIST referral centre. No increase in proportion of central pathology reviews was found. Proportion of patients with mutational analysis increased over the years. The registered incidence of GIST, 17.7 per million inhabitants in 2012 in the Netherlands, is still rising. Despite incorporation in the ESMO GIST guidelines since 2008 for mutational testing and since 2010 for central review of pathology, both are performed in a minority of patients.

A remarkable response to pazopanib, despite recurrent liver toxicity, in a patient with a high grade endometrial stromal sarcoma, a case report.

BACKGROUND: Pazopanib is an oral tyrosine kinase inhibitor registered for metastatic renal cell carcinoma and soft tissue sarcoma. Liver toxicity is a common side effect for this class of agents. The current opinion is that in case of severe liver toxicity pazopanib should be interrupted and restarted at a lower dose after returning to Common Terminology Criteria for Adverse Events (CTCAE) grade 1. After recurrence of liver toxicity at the lower dose it is advised to permanently stop pazopanib. We describe a patient with an YWHAE-FAM22 translocated endometrial stromal sarcoma with a remarkable response to pazopanib despite recurrent liver toxicity. CASE PRESENTATION: A 40 year old woman was diagnosed with metastatic YWHAE-FAM22 translocated endometrial stromal sarcoma. She was treated successively with doxorubicin, megestrol acetate and anastrozole, before pazopanib was initiated. Several dose interruptions and reductions were necessary due to liver toxicity, but nevertheless she had a good partial response. Seven months after the start, pazopanib was permanently stopped because of a bilateral pneumothorax. Nine months later it was reinitiated because of progression and was continued for another 8 months until final disease progression. CONCLUSION: In contrast to the current summary of product characteristics of pazopanib, the drug was successfully continued despite recurrent liver toxicity, and no further liver function deterioration was found. This case suggests that further dose reductions are good practice when liver toxicity limits treatment in responding patients. Secondly, this patient with rare YWHAE-FAM22 translocated endometrial stromal sarcoma showed a remarkable response to VEGFR/KIT inhibitor pazopanib. Recently, it was reported that this specific subtype of endometrial stromal sarcoma overexpresses CD117, but has no KIT mutations. This case illustrates that (a) pazopanib can be continued in patients with recurrent liver toxicity after dose reductions under strict surveillance and that (b) pazopanib shows good efficacy in YWHAE-FAM22 translocated endometrial stromal sarcoma.

Radiation-induced Sarcomas Occurring in Desmoid-type Fibromatosis Are Not Always Derived From the Primary Tumor.

Desmoid-type fibromatosis is a rare, highly infiltrative, locally destructive neoplasm that does not metastasize, but recurs often after primary surgery. Activation of the Wnt/ß-catenin pathway is the pathogenic mechanism, caused by an activating mutation in exon 3 of CTNNB1 (85% of the sporadic patients). Radiotherapy is a frequent treatment modality with a local control rate of approximately 80%. In very rare cases, this may result in the development of radiation-induced sarcoma. It is unclear whether these sarcomas develop from the primary tumor or arise de novo in normal tissue. In 4 tertiary referral centers for sarcoma, 6 cases of desmoid-type fibromatosis that subsequently developed sarcoma after radiotherapy were collected. The DNA sequence of CTNNB1 exon 3 in the desmoid-type fibromatosis and the subsequent postradiation sarcoma was determined. Sarcomas developed 5 to 21 years after the diagnosis of desmoid-type fibromatosis and included 2 osteosarcomas, 2 high-grade undifferentiated pleomorphic sarcomas, 1 fibrosarcoma, and 1 undifferentiated spindle cell sarcoma. Three patients showed a CTNNB1 hotspot mutation (T41A, S45F, or S45N) in both the desmoid-type fibromatosis and the radiation-induced sarcoma. The other 3 patients showed a CTNNB1 mutation in the original desmoid-type fibromatosis (2 with a T41A and 1 with an S45F mutation), which was absent in the sarcoma. In conclusion, postradiation sarcomas that occur in the treatment area of desmoid-type fibromatosis are extremely rare and can arise through malignant transformation of CTNNB1-mutated desmoid fibromatosis cells, but may also originate from CTNNB1 wild-type normal cells lying in the radiation field.

Pneumothorax as adverse event in patients with lung metastases of soft tissue sarcoma treated with pazopanib: a single reference centre case series.

BACKGROUND: Recently, the phase III PALETTE study introduced pazopanib (Votrient®) as treatment for adult patients with locally advanced or metastatic non-liposarcoma soft tissue sarcoma after prior treatment with doxorubicin and/or ifosfamide. Pneumothorax was reported as adverse event in 8 of 246 treated patients (3.3%) in that study. This case series presents the incidence and clinic of this complication in the Leiden University Medical Centre. CASES: Forty-three patients were treated with pazopanib of which six patients (14.0%) developed a pneumothorax. These six patients were treated for malignant peripheral nerve sheath tumour, angiosarcoma, synovial sarcoma, fibromyxomatoid sarcoma, pleomorphic sarcoma and endometrial stromal sarcoma. All six patients had subpleural pulmonary or pleural metastases at the start of pazopanib and the pneumothorax developed during or shortly after treatment with pazopanib and was difficult to treat. DISCUSSION: The incidence reported by us is higher than the incidence in the PALETTE study. Trials with pazopanib in renal cell carcinoma, urothelial carcinoma and cervix carcinoma did not report pneumothorax as an adverse event, suggesting pneumothorax as a specific adverse event in soft tissue sarcoma patients treated with pazopanib. This may be related to the fact that there is often pleural metastatic involvement and cystic degeneration due to pazopanib treatment may add to the risk. CONCLUSION: The risk of an, often difficult to treat, pneumothorax during pazopanib therapy should be discussed with the patient before initiation of treatment for a pulmonary metastasized sarcoma and physicians should be alert to the occurrence of such an event.