Efficacy of receptor tyrosine kinase inhibitors (RTKIs) and immunotherapy (PD-1/PD-L1) for treatment of osseous vs. soft tissue metastases of renal cell carcinoma (RCC).

e16094 Background: Checkpoint inhibitors and RTKIs have changed the standard of care in metastatic RCC. However, anecdotal evidence suggests these therapies may be less effective for treating bone metastases than soft tissue metastases. Our study aimed to evaluate this potential difference in treatment response between osseous and visceral metastases. Methods: Our institutional Cancer Registry database was queried for RCC patients treated at Johns Hopkins Hospital from 1997-2017 (n = 2212). 68 patients were identified with measurable bone and soft tissue metastatic disease who were treated with RTKIs and/or PD-1 inhibitors over the study period. The extent of metastasis was quantified at the time of therapy initiation, 3 mos., 6 mos., and 1 yr. Changes in disease status from baseline were categorized as partial response (PR), complete response (CR), stable (S), mixed (M) or progressive disease (PD) based upon RECISTv1.1 and MDA criteria for soft tissue and bone metastases, respectively. These categories were further organized into Controlled Disease (PR, CR, S) or Evidence of Progression (M, PD) in order to generate a generalized linear effects model with visceral response as the independent variable and bone response as the dependent. Results: Visceral response correlates with bone response at 3 (p = 0.005, n = 76) and 6 months (p = 0.017, n = 48). At 3 mos. 46 patients were treated with RTKI and 30 with PD-1. At 6 mos. 31 patients were treated with RTKI and 17 with PD-1. Of patients with controlled visceral disease, only 19% had progression in bone at 3 mos. (32% at 6 mos.). Of patients with progression in soft tissue, 42% had controlled bone disease at 3 mos. (41% at 6 mos.). Conclusions: This suggests that, contrary to anecdotal reports of a divergent response to biologic therapy, osseous metastases do not appear to respond worse than soft tissue metastases upon treatment with these agents. [Table: see text]

Privacy and Manipulation in the Digital Age

The digital age brings with it novel forms of data flow. As a result, individuals are constantly being monitored while consuming products, services and content. These abilities have given rise to a variety of concerns, which are most often framed using “privacy” and “data protection”-related paradigms. An important, oft-noted yet undertheorized concern is that these dynamics might facilitate the manipulation of subjects; a process in which firms strive to motivate and influence individuals to take specific steps and make particular decisions in a manner considered to be socially unacceptable. That it is important and imperative to battle manipulation carries with it a strong intuitive appeal. Intuition, however, does not always indicate the existence of a sound justification or policy option. For that, a deeper analytic and academic discussion is called for. This Article begins by emphasizing the importance of addressing the manipulation-based argument, which derives from several crucial problems and flaws in the legal and policy setting currently striving to meet the challenges of the digital age. Next, the Article examines whether the manipulation-based concerns are sustainable, or are merely a visceral response to changing technologies which cannot be provided with substantial analytical backing. Here the Article details the reasons for striving to block manipulative conduct and, on the other hand, reasons why legal intervention should be, in the best case, limited. The Article concludes with some general implications of this discussion for the broader themes and future directions of privacy law, while trying to ascertain whether the rise of the manipulation-based discourse will lead to information privacy’s expansion or perhaps its demise.

‘Vein by Vein’: The Pneumatics of Retribution in John Marston’s Antonio’s Revenge

This chapter argues that John Marston’s Antonio’s Revenge adopts a Galenic understanding of corporeal pneumatics to debunk Stoic apatheia and reveal it as inherently incompatible with nature. Marston’s play not only represents the body’s subtlest operations as instinctively countering the trauma wrought by tragedy through its pneumatic systems. He also, by affiliating revenge with a pneumatic process of instinctive self-healing, undercuts Stoicism's broader cosmological notion of pneuma as a “containing cause,” a pervasive force that imbues the universe with rationality and provides for the Stoic sage tranquility amid suffering. By appropriating Galen's theory of corporeal pneumatics and sharing the physician-philosopher's anti-stoic sentiment, Marston creates an ontological framework for his play that situates Antonio's final vengeance as acting in accordance with how his world, at its most rudimentary levels, operates. Drawing on Galenic medical theory and anti-stoic philosophy, Marston surprisingly figures retribution as physiologically beneficial, a visceral response to trauma that addresses the body’s intrinsic need for constitutional equilibrium. In doing so, Marston’s play introduces a therapeutic register to revenge attentive, unlike the rigors of Stoicism, to the body's inherent impulse – extending even to its most attenuated material components – toward attaining palliation for the debilitating effects of physical and emotional trauma.

Everyday Moments

Chapter two seeks to reframe the way in which we approach the affective potential of extreme cinema by investigating an implicit dynamic at work in its reception: the distinction between an immediate visceral response, and a more pervasive enduring kind of affect. Arguing that the triangulation of disturbing affect, the violent, and the everyday is not purely a recent phenomenon, chapter two traces two lines of continuity between past and recent extreme cinema. The first thread is a “discourse of immediacy”: the tendency of critics and scholars to privilege immediate visceral responses such as shock, outrage and disgust when articulating the kinds of affect extreme films produce. Secondly, the chapter reveals that the aesthetic tension between the extreme and the everyday is observable in films prior to the new extremism, albeit in more discreet ways. This latter argument is demonstrated through detailed studies of Pier Paolo Pasolini’s Salò or the 120 Days of Sodom (1975) and Elem Klimov’s Come and See (1985). Significant not only for their notoriety as extreme, but because despite their seeming incongruence with the everyday, their subtle gestures towards it at key moments is crucial to their affective quality, these films signal that the distinction between the extreme and the everyday is not necessarily clear cut.