Thermal performance is a key component of fitness particularly for ectotherms living in thermally variable environments. Local adaptation can occur within populations of a species that inhabit regions with divergent thermal conditions, but this adaptation may result in trade-offs in other measures of fitness. If these trade-offs affect other aspects of thermal performance, several different patterns are possible (Huey and Kingsolver 1993). One potential pattern from a trade-off is a shift in the thermal niche, meaning that an or¬ ganism that can handle a new range of higher temperatures can no longer handle colder temperatures as well. A second type of pattern is a generalist/specialist trade-off whereby populations may have broader thermal niches but lower fitness at optimal temperatures [i.e. "a jack-of-all-trades is a master of none" (Huey and Hertz 1984)]. Another possibility is that increased investment associated with local thermal adaptation (i.e. high tempera¬ ture tolerance) may result in trade-offs in non-thermally dependent traits (Angilletta et al. 2003). The nature and structure of these trade-offs could determine the degree to which organisms will be able to respond to a changing climate.The copepod Tigriopus californicus (Baker, 1912) has become an important system in which to study the evolution of local adaptation to the thermal environment. Geographi¬ cally distinct populations of this copepod occur in upper intertidal pools along the Pacific coast from central Baja Mexico to Alaska. These populations often show high degrees of genetic divergence from one another indicating that levels of gene flow between popula¬ tions can be very limited over long periods of time (Burton 1997;Edmands 2001; Willett and Ladner 2009). There is also a clear latitudinal gradient in high temperature survival that is suggestive of local thermal adaptation for this species (Willett 2010;Kelly et al. 2012;Leong et al. 2018). This latitudinal gradient for high temperature tolerance has been seen for nauplii and copepodids as well as adults (Tangwancharoen and Burton 2014).Local thermal adaptation in T. californicus is also suggested by studies of fitness com¬ ponents and competitive fitness under non-extreme temperatures. Hong and Shurin (2015) examined 15 populations of T. californicus from Vancouver Island, BC, Canada, to south¬ ern California (CA) for a set of life history traits that contribute to fitness under four different temperature conditions (from 15°C to 30°C). They estimated the net fitness ef¬ fect of these traits by calculating an intrinsic population growth rate (r) and found a con¬ sistent shift in the thermal niche from south to north and also higher r in the northern populations. Willett (2010) also found that for comparisons across a set of moderate tem¬ peratures there was a flip in competitive fitness between pairs of southern and central CA T. californicus populations. Central CA populations outcompeted southern populations at 16°C while the opposite pattern was observed in a fluctuating environ...
BackgroundImmune checkpoint inhibitors (ICIs) are used to treat locally-advanced and metastatic lung cancer, which can lead to severe immunogenic-related cardiotoxicities. We assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy.MethodsRetrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed in correlation with the timing of radiotherapy (RT) in relation to ICI, and the mean RT heart dose. The rate of cardiac events in relation to RT timing and heart dose was compared using multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy.ResultsOf 194 ICI-treated patients evaluated, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). 38 patients who received RT concurrently with ICI did not develop any cardiotoxicity whereas 14.1% (n=22/156) of those who did not receive concurrent RT developed cardiotoxicities (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.ConclusionICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy in this retrospective review. Further validation of prospective studies is needed to confirm these results.
BackgroundImmune checkpoint inhibitors (ICIs) are used in the treatment of locally advanced and metastatic lung cancer. ICIs can lead to severe immunogenic related cardiotoxicities. The cardiotoxic profile of these agents when combined with thoracic radiotherapy is not well-defined. Here, we assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy. Methods Retrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed by cardiologists and medical oncologists in correlation with the timing of RT in relation to ICI and the mean RT heart dose. RT was delivered between cycles of immunotherapy for patients who received RT concurrently with ICI. Multivariate analysis on the rate of cardiac events/cardiotoxicity in relation to radiotherapy timing and heart dose was performed on multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy.ResultsOf 194 ICI-treated patients evaluated, 66 (34.02%) and 128 (65.98%) had Stage III and IV SCLC or NSCLC, respectively, the median age was 64 years (range, 36-88), and 42.47% were female. Within the total cohort, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). There were 38 patients who received RT concurrently with ICI and did not develop any cardiotoxicity whereas cardiotoxicity was observed in 14.1% (n=22/156) of those who did not receive concurrent RT (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI.ConclusionICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy. Univariate analysis suggests a potential cardioprotective effect of thoracic RT with ICI’s, which may be due to modulation of the immune response through reduction of lymphocytes involved in autoimmune processes.
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