Current Treatment Considerations in Metastatic Renal Cell Carcinoma

OPINION STATEMENT: In general, debulking neprhectomy is still considered for metastatic RCC patients with primary tumor in place, assuming good performance status. Initial systemic therapy should consider high-dose IL-2 for the highly select patient. One reason for initial consideration of this therapy is the less certain risk/benefit profile if employed after targeted therapy. Notably, due to its potential toxicity and emergence of new effective and more tolerable drugs, IL-2 has become a less favorable and subsequently a less utilized therapeutic tool in the current era. Otherwise, VEGF-targeted therapy is the treatment of choice, preferably on a clinical trial. Off trial, sunitinib has long been favored but pazopanib is gaining more use for tolerance pending the comparative trial. Continued VEGF targeting is favored by these authors given the underlying biology of RCC and the prospective clinical data, noting no direct comparison of mTOR and VEGF agents has yet occurred. Maintaining patient dose is critical and requires optimal supportive care and appreciation/early intervention for toxicity. Predictive biomarkers are desperately needed, and enrollment on clinical trials remains a priority to optimize patient outcome.     

Treatment of renal cell carcinoma: Current status and future directions

Answer questions and earn CME/CNE Over the past 12 years, medical treatment for renal cell carcinoma (RCC) has transitioned from a nonspecific immune approach (in the cytokine era), to targeted therapy against vascular endothelial growth factor (VEGF), and now to novel immunotherapy agents. Multiple agents—including molecules against vascular endothelial growth factor, platelet‐derived growth factor, and related receptors; inhibitors of other targets, such as the mammalian target of rapamycin and the MET and AXL tyrosine‐protein kinase receptors; and an immune‐checkpoint inhibitor—have been approved based on significant activity in patients with advanced RCC. Despite these advances, important questions remain regarding biomarkers of efficacy, patient selection, and the optimal combination and sequencing of agents. The purpose of this review is to summarize present management and future directions in the treatment of metastatic RCC. CA Cancer J Clin 2017;67:507‐524. © 2017 American Cancer Society.     

Efficacy and safety of deep sedation by non-anesthesiologists for cardiac MRI in children

Background

Cardiac MRI has become widespread to characterize cardiac lesions in children. No study has examined the role of deep sedation performed by non-anesthesiologists for this investigation.

Objective

We hypothesized that deep sedation provided by non-anesthesiologists can be provided with a similar safety and efficacy profile to general anesthesia provided by anesthesiologists.

Materials and methods

This is a retrospective chart review of children who underwent cardiac MRI over a 5-year period. The following data were collected from the medical records: demographic data, cardiac lesion, American Society of Anesthesiologists (ASA) physical status, sedation type, provider, medications, sedation duration and adverse events or interventions. Image and sedation adequacy were recorded.

Results

Of 1,465 studies identified, 1,197 met inclusion criteria; 43 studies (3.6%) used general anesthesia, 506 (42.3%) had deep sedation and eight (0.7%) required anxiolysis only. The remaining 640 studies (53.5%) were performed without sedation. There were two complications in the general anesthesia group (4.7%) versus 17 in the deep sedation group (3.4%). Sedation was considered inadequate in 22 of the 506 deep sedation patients (4.3%). Adequate images were obtained in 95.3% of general anesthesia patients versus 86.6% of deep sedation patients.

Conclusion

There was no difference in the incidence of adverse events or cardiac MRI image adequacy for children receiving general anesthesia by anesthesiologists versus deep sedation by non-anesthesiologists. In summary, this study demonstrates that an appropriately trained sedation provider can provide deep sedation for cardiac MRI without the need for general anesthesia in selected cases.     

Adaptive immune contexture at the tumour site and downmodulation of circulating myeloid-derived suppressor cells in the response of solitary fibrous tumour patients to anti-angiogenic therapy

Background:

Host immunity is emerging as a key player in the prognosis and response to treatment of cancer patients. However, the impact of the immune system and its modulation by therapies are unknown in rare soft tissue sarcomas such as solitary fibrous tumours (SFTs), whose management in the advanced forms includes anti-angiogenic therapy. Here, we studied the in situ and systemic immune status of advanced SFT patients and the effects of sunitinib malate (SM) in association with the clinical efficacy.

Methods:

Immune contexture of SFTs was assessed by immunohistochemistry in lesions from untreated or SM-treated patients. Frequency of circulating myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs) and T-cell functions was assessed ex vivo in SFT patients prior and during anti-angiogenic therapy. Patients with long-term tumour control were included to correlate immune profiles and clinical responses.

Results:

Anti-angiogenic naïve SFT lesions were heavily infiltrated by CD163⁺CD14⁺CD68⁻ and CD163⁺CD14⁻CD68⁻ myeloid cells but devoid of T cells. Conversely, post-SM tumours acquired a new subset of CD68⁺CD14⁺ myeloid cells and displayed traits of an on-going adaptive immunity, strongly enriched in activated CD8⁺ and CD4⁺ T cells. These changes at the tumour site paralleled the alleviation of systemic immunosuppression and the drop in the frequency of circulating monocytic MDSCs (mMDSCs) and granulocytic MDSCs (gMDSCs). Rebound in the number of mMDSCs, but not of gMDSCs occurred at disease progression, and a reduced percentages of mMDSCs, comparable to those found in healthy donors (HDs), endured only in the SM-responsive patients.

Conclusions:

The immune contexture of SFT patients is heavily involved in anti-angiogenic therapy and it could be exploited to achieve more durable disease control through immune-based combination strategies.     

Molecular genetics of hereditary renal cancer: new genes and diagnostic and therapeutic opportunities

Renal cell carcinoma may be sporadic or occur in the setting of an inherited cancer syndrome, such as von Hippel-Lindau or Birt-Hogg-Dube syndrome. Although the clinical spectrum of heritable renal cancer syndromes varies significantly, commonalities include the often young age of presentation, multifocal and bilateral nature of renal lesions, and autosomal dominant pattern of inheritance. Molecular studies have recently begun to elucidate the genetic abnormalities and subsequent alterations in downstream intracellular signaling cascades that underlie the development of these syndromes. This review will highlight the clinicopathologic and molecular features associated with the diverse array of heritable renal cancer syndromes and emphasize the potential cellular pathways that may be utilized to develop novel treatment strategies for patients with these syndromes.