Management and Outcomes of Older Patients (Age ≥ 70 Years) with Advanced Soft Tissue Sarcoma and Role of Geriatric Assessment and Oncological Multidimensional Prognostic Index (Onco-MPI) in a Real-World Setting.

Background: Incidences of soft tissue sarcomas (STS) steadily increase with age. Yet, despite the high prevalence in advanced age, older patients (pts) are underrepresented in sarcoma clinical trials and evidence-based guidelines for chemotherapy are lacking. International oncological societies suggest using geriatric tools to evaluate older patients with cancer to optimise treatment indication. Comprehensive geriatric assessment (CGA) is a multidimensional assessment of older subjects, based on which pts can be classified as fit, vulnerable or frail. Onco-MPI (multidimensional prognostic index) is a CGA-based score which also considers tumour characteristics, classifying pts into three risk groups of death at one year: high-risk, intermediate-risk and low-risk. Methods: This is a single-centre retrospective study which aims at describing real-word management and outcomes of older pts with advanced stage STS and at assessing the ability of CGA and onco-MPI to predict survival in these pts. Consecutive pts with advanced stage STS aged 70 years or older and treated at the Istituto Oncologico Veneto from January 2009 to June 2020 were retrieved from a prospectively maintained database. Pts' demographics, CGA assessments and tumour characteristics were analysed. Statistical analysis was performed with R version 3.4.3 Results: Out of 101 pts, with a median age of 77 years, 76 received chemotherapy (75.3%), which was anthracycline-based for 46 pts (60.5%). Anthracyclines were used in a higher proportion in fit pts (58.9% fit vs. 45.1% vulnerable vs. 12.5% frail pts). Frail pts and pts in the onco-MPI high-risk group experienced a higher rate of chemotherapy-related toxicities. Median OS was 13.8 months (95% CI 11.3-17.7 months). According to CGA, the median OS was 19.53 months (95% CI 15.23-36.8) for fit pts, 12.83 months (95% CI 9.7-17.5) for vulnerable and 7.75 months (95% CI 2.73-30) for frail pts (p = 0.005). Onco-MPI confirmed a predictive value for 1-year survival with intermediate risk pts not reaching a median OS at 1 year, and high-risk pts having a median one-year OS of 11.5 months (95%CI 9.7-NA), p = 0.02. In multivariate analysis, onco-MPI and CGA were associated with survival (high risk onco-MPI: HR 5.5, 95%CI 1.25-24.7 p = 0.02; fitness at CGA HR 0.552 95% 0.314-0.973; p = 0.040) as well as chemotherapy use (HR 0.24, 95% CI 0.11-0.51, p < 0.005). Conclusions: Both CGA and onco-MPI retain prognostic value for survival in pts with metastatic STS. Pts frail/vulnerable at CGA and pts within the onco-MPI high risk category should be offered an oncogeriatric management approach in order to optimise treatment-related survival and reduce toxicity.

Trabectedin and Radiation Therapy for Cardiac Metastasis From Leiomyosarcoma: A Case Report and Review of the Literature.

Leiomyosarcoma (LMS) is one of the most frequent subtypes of soft-tissue sarcomas (STSs). Metastatic spread to the heart in cancer patients carries a poor prognosis and there is no known effective treatment. Cardiac metastases of STSs are very rare. Here we present the case of a 55-year-old patient who underwent surgical resection of a retroperitoneal leiomyosarcoma and then developed widespread metastatic disease, treated with a combination of local treatment and systemic therapy. Three years after surgical resection she presented with a cardiac intraventricular mass, which was treated with radiation therapy, while receiving systemic therapy with trabectedin. Such combination therapy was well-tolerated and effective, allowing a substantial dimensional reduction which is perduring to date, 18 months after diagnosis of cardiac metastasis. Available literature and data point to the feasibility and good tolerability of radiation therapy and trabectedin in metastatic sarcoma, yet this is the first report on the effectiveness of the combination for the treatment of cardiac disease. The extended survival since a metastatic relapse (more than 3 years) is likely the result of integrated systemic and loco-regional treatment, which should be always discussed within the framework of a multiprofessional and multidisciplinary setting.

Cardiotoxicity from Capecitabine Chemotherapy: Prospective Study of Incidence at Rest and During Physical Exercise.

BACKGROUND: Physical activity may increase the risk of cardiotoxicity (myocardial ischemia, major arrhythmias) of 5-Fluorouracil, but this risk has never been investigated for its prodrug capecitabine. PATIENTS AND METHODS: One hundred and ninety-two consecutive patients undergoing capecitabine chemotherapy from December 1, 2010 through July 31, 2016 were prospectively evaluated. The baseline evaluation included electrocardiography (ECG) and echocardiography (2DE); a follow-up evaluation, including ECG and exercise stress testing (2DE in case of ECG abnormalities), was done after ≥10 days of treatment. Cardiotoxicity was suspected from ischemic ECG changes, new kinetic abnormalities at 2DE, Lown classification ≥2 ventricular arrhythmia, symptomatic arrhythmias, or positive stress test, and confirmed by a negative stress test after capecitabine washout. RESULTS: Cardiotoxicity was diagnosed in 32 patients (16.7%): six at rest and 26 during exercise. All 32 patients had ECG abnormalities: ST-segment changes (24 patients), negative T-waves (2) and/or arrhythmias: ventricular arrhythmias (14 cases), supraventricular tachycardia (2), complete heart block (1). Eight patients had typical symptoms, 6 had atypical symptoms, 1 had syncope, 17 (53%) were asymptomatic. Cardiotoxicity was more common in patients with atypical symptoms during daily life (OR = 15.7) and in those on a therapeutic schedule of 5 days/week (OR = 9.44). CONCLUSION: Capecitabine cardiotoxicity is frequent, and often elicited by physical effort. Oncologists, cardiologists, and general practitioners should be aware of this risk. Active cardiotoxicity surveillance with ECG (and echocardiogram and/or stress testing in suspected cases) during therapy is recommended. CLINICAL TRIALS REGISTRATION NUMBER: CRO-2010-17.

Neoplastic Pericardial Effusion: A Monocentric Retrospective Study.

Background: Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. Objective: We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients. Design: We reviewed clinical, pathological, and echocardiographic features, therapeutic strategies, and outcome in NPE patients referred to our institute from August 2011 to December 2017. Measurements: Twenty-nine patients with NPE from solid tumors have been identified: 21 lung, 5 breast, and 3 other cancer patients. Results: Median age was 62 years. Most of the patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (69%) and a symptomatic NPE (69%). In 52% of patients NPE was detected at first diagnosis of metastatic disease, and in 20% of patients pericardium was the only site of metastases. Most of the patients (62%) received systemic therapy, 28% received combined locoregional and systemic therapy, and 10% received locoregional therapy alone. Median overall survival (OS) from NPE diagnosis was 3.9 months. Patients with PS ≥2 had worse OS than patients with better PS <2 (hazard ratio [HR] 3.56, IC 95% 1.19-10.65, p 0.02). Older age, extrapericardial disease, and NPE at progression showed a trend of association with worse OS. Patients treated with locoregional therapy alone showed the shortest median OS (p 0.05). Conclusions: NPE is related to dismal prognosis. Poor PS significantly worsens survival and influences therapeutic approaches. Randomized studies are required to investigate prognostic factors and appropriate clinical management for patients with NPE.

Opacification patterns of cardiac masses using low-mechanical index contrast echocardiography: comparison with histopathological findings.

BACKGROUND: Two-dimensional echocardiography is the main noninvasive imaging tool to identify cardiac masses but is unable to provide detailed tissue characterization. AIM: The aim of the study was to assess the ability of low mechanical index (MI) contrast echocardiography to detect presence and amount of tissue vascularization as validated by histopathology study of cardiac masses. METHODS AND RESULTS: Twelve consecutive patients (5 females and 7 males, age range 51-82 years) underwent conventional and contrast two-dimensional echocardiography with low MI. By contrast echocardiography, mass enhancement was classified as absent (suggesting thrombus), partial, or complete (suggesting vascularized mass, both with early or late >20 cycles of opacification) as compared to the adjacent myocardium. The precise nature of the cardiac masses was provided by histopathology examination and/or by resolution after anticoagulation therapy during follow-up. Presence, type, and degree of mass vascularization were assessed by histology, immunohistochemistry, and morphometric analysis. Among the 12 cases, mass enhancement was absent, late and peripheral, late and partial, and early and complete in three cases each. Cardiac masses consisted of thrombus (three), secondary malignant cardiac tumor (three), myxoma (three), papillary fibroelastoma (two), and cavernous hemangioma (one). At histology, cardiac hemangioma had the highest degree of vascularization, at difference from thrombi which were not vascularized, and data were in keeping with contrast echocardiography findings. CONCLUSIONS: Low MI contrast echocardiography is an easy, noninvasive cardiac imaging tool to assess cardiac mass vascularization. The degree of contrast enhancement and time to opacification are highly variable among cardiac masses and correspond to different extent of vascularization.

Role of dose exposure and inflammatory status in a single center, real-world analysis of sunitinib in patients with metastatic renal cell carcinoma.

UNLABELLED: AIM, PATIENTS & METHODS: To evaluate the real-world setting use of sunitinib, we reviewed data of our patients from January 2007 to December 2014. RESULTS: In 114 patients, sunitinib was used as first-line TKI. Out of 110 evaluable patients, 5 complete responses, 37 partial responses, 42 stabilizations were reported. Median progression-free survival and overall survival (OS) were 14.3 and 28.4 months. Patients who received ≥ 4 full-dose cycles had a better OS (p = 0.02). A neutrophil-lymphocyte ratio <3 was associated both with OS and progression-free survival (50.4 vs 8.4 and 20.0 vs 3.3 months). CONCLUSION: Sunitinib is active and feasible. Patients receiving <4 full-dose cycles or having increased neutrophil-lymphocyte ratio achieved worse outcomes: therefore, these are present potential predictive factors.

Unusual echocardiographic appearance of a cardiac metastasis from lung carcinoma.

During hospitalization in the Oncology Department, a woman with nonsmall cell lung cancer and no previous cardiac event complained of episodes of chest pain and palpitations. Preliminary instrumental examinations diagnosed atrial fibrillation in pericarditis. A subsequent complete transthoracic echocardiogram showed the presence of a large mass involving the left ventricular apex, without echo-contrast enhancement. A thoracic CT with iodized contrast agent revealed its necrotic composition and was concluded as cardiac metastasis. This is an unusual case of a malignant neoplasm showing no contrast enhancement at echocardiogram because of its necrotic composition, mimicking a thrombus. © 2015 Wiley Periodicals, Inc. J Clin Ultrasound 44:392-394, 2016.

Hypertension as a biomarker in patients with recurrent glioblastoma treated with antiangiogenic drugs: a single-center experience and a critical review of the literature.

Treatment with angiogenesis inhibitors is becoming a cornerstone of modern anticancer therapy. Hypertension (HTN) is a common adverse event during antiangiogenic treatment and might represent a cancer biomarker in patients with recurrent glioblastoma treated with angiogenesis inhibitors. In a retrospective study, we analyzed 53 patients with recurrent glioblastoma treated with antiangiogenic drugs. Thirty patients were treated with sorafenib and 23 patients were treated with bevacizumab. All patients underwent brain gadolinium-enhanced MRI assessments according to the Radiologic Assessment in Neuro-Oncology criteria every 2 months or when clinically indicated. Blood pressure was measured before and during the treatment. We investigated whether treatment-related HTN may be associated with outcome in patients treated with antiangiogenic drugs. After 2 months of treatment, 24 patients (45%) achieved disease control: stable disease (17 patients) or a partial response (seven patients). The median overall survival from the start of antiangiogenic treatment was 7.3 months [95% confidence interval (CI) 6.02-8.5]; the median progression-free survival (PFS) was 2.7 months (95% CI 1.5-3.5); and the 6-month PFS was 32%. Twenty patients (38%) developed grades 2-3 HTN within 2 months of treatment. A significant association was found between HTN and disease control rate, and HTN and 6-month PFS; no significant association was found between HTN and the median PFS. According to univariate and multivariate analyses, HTN was related to a longer survival from antiangiogenic drug administration: 9.8 versus 4.8 months (P=0.001; hazard ratio=3.5, 95% CI 1.6-7.6). Our data indicate that HTN may be an effective biomarker in patients with recurrent glioblastoma treated with antiangiogenic drugs; in particular, it may be associated with a favorable effect on disease control, 6-month PFS, and the median overall survival.

Bi-weekly liposomal doxorubicin for advanced breast cancer in elderly women (≥ 70 years).

BACKGROUND: We conducted a multicenter prospective trial to assess tolerability and activity of pegylated liposomal doxorubicin (PLD) in women ≥ 70 years with locally-advanced or metastatic breast cancer. PATIENTS AND METHODS: All patients underwent Multidimensional Geriatric Assessment (MGA). Frail patients were excluded. Normal cardiac function was required for inclusion. A bi-weekly schedule of PLD at 20mg/mq was adopted. RESULTS: Thirty-two patients were enrolled with a median age of 78 years, 78.1% with visceral involvement, and 37.6% previously treated with chemotherapy for advanced disease. A mean of 7.8 cycles were delivered (range 1 to 20), with a median cumulative dose intensity of 8.9 mg/m(2)/week. Grade 3-4 toxicities were anemia (6.3%), palmar-plantar erythrodysesthesia (6.3%), mucositis (6.3%), infection (3.1%), and pulmonary embolism (3.1%). No cardiac events were registered. Causes of treatment interruption were maximal response (15.6%), progression (40.6%), refusal/loss to follow-up (28.1%), toxicities (9.4%), or other (6.3%). Response was obtained in 33.3% of 27 evaluable patients; median time to progression (TTP) was 10.3 months. MGA status (vulnerable vs. fit) did not have an impact on response, progression, and toxicity. CONCLUSIONS: Bi-weekly PLD is well tolerated in both fit and vulnerable patients, with an apparently fairly good response rate and TTP (possibly biased by subsequent endocrine therapy and loss to follow-up). Close observation of patients is recommended in order to avoid early refusal/loss to follow-up.

An unusual mediastinal outline.

Thymoma is the most common primary neoplasm of the anterior mediastinum. We describe the case of a 40-year-old man with asymptomatic thymoma involving the right atrium, and the diagnostic pathway.

Low molecular weight heparin (parnaparin) for cardioembolic events prevention in patients with atrial fibrillation undergoing elective electrical cardioversion: a prospective cohort study.

Systemic thromboembolism is a severe complication in patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Vitamin K antagonists greatly reduce the risk of thromboembolic events, but the administration scheme before ECV is troublesome as difficulties in reaching and maintaining the target therapeutic range for 3 weeks often delay the restoration and likelihood of maintaining sinus rhythm. Low molecular weight heparins (LMWHs) do not need dose adjustment, and may be preferable in this clinical setting. In this multicentre study, the LMWH parnaparin was used at a dose of 85 anti-factor Xa U/kg b.i.d. 2 weeks before and 3 weeks after ECV of AF. In an intention to treat analysis of 102 patients, there was no systemic thromboembolism or major bleeding (0%, 95% CI 0-3.6). Two clinically relevant non-major bleeds (2.5%, 95% CI 0.7-8.8) and three minor bleeds (3.8%, 95% CI 1.3-10.6) were recorded. No heparin-induced thrombocytopenia or other major adverse events were recorded. Parnaparin appears effective and safe for thromboprophylaxis of elective ECV in patients with AF.

Large infero-posterior wall pseudoaneurysm of the left ventricle: an unusual presentation.

Post-myocardial infarction left ventricular pseudoaneurysm resulting from free wall rupture is a rare finding and its recognition during life is uncommon. The diagnosis is difficult since symptoms, clinical evaluation and electrocardiographic and X-ray findings are usually non-specific. We herein present a case of a pseudoaneurysm manifesting after a silent myocardial infarction and diagnosed at echocardiography in a patient who, at the time of hospitalization, had a history and clinical and laboratory findings suggestive of pulmonary embolism. The patient was successfully operated. The present report underlines the diagnostic and prognostic value of two-dimensional transthoracic echocardiography. The clinical and laboratory findings are also discussed in the light of the recent literature.