BackgroundManipulation of immune checkpoints such as CTLA4 or PD-1 with targeted antibodies has recently emerged as an effective anticancer strategy in multiple malignancies. Sarcomas are a heterogeneous group of diseases in need of more effective treatments. Different subtypes of soft tissue and bone sarcomas have been shown to express PD-1 ligand.MethodsWe retrospectively analyzed a cohort of patients (pts) with relapsed metastatic/unresectable sarcomas, who were treated with nivolumab provided under a patient assistance program from the manufacturer. Pts underwent CT or PET/CT imaging at baseline and after at least four doses of nivolumab; RECIST 1.1 criteria were used for response assessment.ResultsTwenty-eight pts with soft tissue (STS, N = 24) or bone sarcoma (N = 4), received IV nivolumab 3 mg/kg every 2 weeks from July 2015. Median age was 57 (24–78), male:female ratio was 14:14; the median number of nivolumab cycles was eight. Eighteen pts concomitantly received pazopanib at 400–800 mg daily. The most common side effect was grade 1–2 LFT elevations; grade 3–4 toxicity occurred in five patients (colitis, LFT elevations, pneumonitis). Twenty-four pts received at least four cycles. We observed three partial responses: one dedifferentiated chondrosarcoma, one epithelioid sarcoma and one maxillary osteosarcoma (last two patients on pazopanib); nine patients had stable disease including three leiomyosarcomas; 12 patients had progression of disease including 4 leiomyosarcoma. Clinical benefit (response + stability) was observed in 50% of the evaluable patients.ConclusionsThese data provide a rationale for further exploring the efficacy of nivolumab and other checkpoint inhibitors in soft tissue and bone sarcoma.Electronic supplementary materialThe online version of this article (doi:10.1186/s13569-016-0064-0) contains supplementary material, which is available to authorized users.
Primary systemic therapy (PST) or neoadjuvant therapy is used in nonmetastatic breast cancer to treat systemic disease earlier, decrease tumor bulk ideally to a complete pathological response (pCR), and reduce the extent of surgery. The multitude of clinical trials using PST in breast cancer patients has not proven the fundamental hypotheses of improved overall survival and disease-free survival that drove the investigation of PST. The other potential advantages of PST, which include increasing the rate of breast-conserving surgery and predicting outcome to a particular chemotherapy regimen, are also not conclusively established. We examined the published literature on PST for breast cancer and predominantly focused our review on data from large, randomized clinical trials comparing primary systemic chemotherapy with adjuvant chemotherapy, different primary systemic chemotherapy regimens, primary systemic chemotherapy with hormonal therapy, and different preoperative hormonal therapies. Although the optimal neoadjuvant chemotherapy regimen has not been established, a combination of four cycles of an anthracycline followed by four cycles of a taxane appears to produce the highest pCR rate (22%-31%). In patients with HER-2-positive breast cancer, concurrent use of neoadjuvant trastuzumab with an anthracycline-taxane combination has produced provocative results that require further confirmatory studies. Preoperative hormonal therapy is associated with low pCR rates and should be reserved for patients who are poor candidates for systemic chemotherapy. The optimal management of patients with residual disease after the administration of maximum neoadjuvant therapy remains to be defined. The surgical approach, including the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients, is evolving. Ongoing clinical trials will help identify the subset of patients who would most benefit from the use of PST, establish the most effective PST regimen, and determine the optimal multidisciplinary approach in the management of breast cancer. The Oncologist 2006;11:574-589 Learning ObjectivesAfter completing this course, the reader will be able to:1. Describe the rationale for using primary systemic therapy (PST) in the treatment of nonmetastatic breast cancer.2. Discuss the pathologic complete response (pCR) rate as a surrogate marker of PST benefit.3. Select the most appropriate regimen for a patient with breast cancer considered for PST.4. Explain the role of sentinel node biopsy and delivery of radiation therapy after PST in breast cancer patients.Access and take the CME test online and receive 1 AMA PRA category 1 credit at CME.TheOncologist.com CME CME This material is protected by U.S.
Cardiac k-factors for all scanners and protocols are considerably higher than the k-factor currently used to estimate ED of cardiac CT studies, suggesting that radiation doses from cardiac CT have been significantly and systematically underestimated. Using cardiac-specific factors can more accurately inform the benefit-risk calculus of cardiac-imaging strategies.
AIMTo assess the accuracy of shear wave elastography (SWE) alone and in combination with aminotransferase platelet ratio index (APRI) score in the staging of liver fibrosis.METHODSA multicenter prospective study was conducted to assess the accuracy of SWE (medians) and APRI to predict biopsy results. The analysis focused on distinguishing the different stages of liver disease, namely, F0 from F1-4, F0-1 from F2-4, F0-2 from F3-4 and F0-3 from F4; F0-F1 from F2-F4 being of primary interest. The area under the receiver operating characteristic (AUROC) curve was computed using logistic regression model. The role of age, gender and steatosis was also assessed.RESULTSSWE alone accurately distinguished F0-1 from F2-4 with a high probability. The AUROC using SWE alone was 0.91 compared to 0.78 for using the APRI score alone. The APRI score, when used in conjunction with SWE, did not make a significant contribution to the AUROC. SWE and steatosis were the only significant predictors that differentiated F0-1 from F2-4 with an AUROC of 0.944.CONCLUSIONOur study validates the use of SWE in the diagnosis and staging of liver fibrosis. Furthermore, the probability of a correct diagnosis is significantly enhanced with the addition of steatosis as a prognostic factor.
Positron emission tomography (PET) is a functional imaging technique with important clinical applications in cardiology, oncology, and neurology. In cardiac imaging, its role has been extensively evaluated in the noninvasive diagnosis of coronary artery disease and in the determination of prognosis. Additionally, cardiac PET with F-18 fluorodeoxyglucose (FDG) is very helpful in selection of patients with coronary artery disease and left ventricular dysfunction who would benefit from coronary artery revascularization. Cardiac PET is arguably considered by many as a gold standard in this particular application. F-18, unlike other positron emitters, has a reasonably long physical half-life, which permits its distribution through commercial radiopharmacies. This is further facilitated by increasing popularity of FDG PET in oncology, which makes cardiac FDG PET a practical option for hospitals and outpatient centers equipped with PET scanners. In addition, gamma camera single photon emission computed tomography (SPECT) systems, routinely used in nuclear medicine departments, can be equipped with coincidence circuit or high-energy 511 KeV collimators, providing a cost-effective means of FDG cardiac imaging. Myocardial utilization of glucose as a substrate is variable, depending, among other factors, on serum levels of glucose and insulin. Therefore, patient preparation is important in obtaining good-quality images and in turn allowing for accurate interpretation of myocardial viability. There are various protocols to choose from that provide diagnostic image quality in both diabetic and nondiabetic patients. Mismatch between blood flow and FDG metabolism, an indicator of viable, jeopardized myocardium, can predict postrevascularization improvement in left ventricular function, symptomatic relief, and long-term survival.
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