Tumor Volume Nadir in Patients With ALK-Rearranged Non-Small-Cell Lung Cancer Treated With Alectinib.

PURPOSE: Patients with oncogene-driven advanced non-small-cell lung cancer (NSCLC) treated with effective targeted therapy demonstrate characteristic tumor volume dynamics with initial response, nadir, and subsequent regrowth. This study investigated tumor volume nadir and time to nadir in patients with ALK-rearranged advanced NSCLC treated with alectinib. MATERIALS AND METHODS: In patients with advanced ALK-rearranged NSCLC treated with alectinib monotherapy, tumor volume dynamics were evaluated on serial computed tomography (CT) scans using a previously validated CT tumor measurement technique. A linear regression model was built to predict tumor volume nadir. Time-to-event analyses were performed to evaluate time to nadir. RESULTS: Among 45 patients who experienced initial volume decrease, 37 patients (25 with tumor regrowth and 12 without regrowth but >6 months follow-up) were studied for nadir volume (Vp). The linear model to predict tumor volume nadir was built using the baseline tumor volume (V0): V0-Vp = .696 × V0 + 5,326 (P < 2 × 10-16; adjusted R2 = 0.86). The percent volume changes at nadir (median, -90.9%, mean, -85.3%) showed larger decrease in patients who were treated with alectinib as first-line therapy than in the ≥2nd-line group and were independent of V0 and clinical variables. Time to nadir had a median of 11.5 months and was longer in the first-line group (P = .04). CONCLUSION: The tumor nadir volume in patients with ALK-rearranged advanced NSCLC treated with alectinib can be predicted by the liner regression model and consists of approximately 30% of the baseline volume minus 5 cm3, providing additional insights into precision therapy monitoring and potential guides for local ablative therapy to prolong disease control.

Down-regulation of love feelings after a romantic break-up: Self-report and electrophysiological data.

Because remaining love feelings for an ex-partner are negatively associated with recovery from a romantic break-up, it may be helpful to decrease those love feelings. Love regulation is the use of behavioral or cognitive strategies to change the intensity of current feelings of romantic love. This study evaluated three regulation strategies: (1) negative reappraisal of the ex-partner, (2) reappraisal of love feelings, and (3) distraction. It was tested how these regulation strategies change love feelings for the ex-partner, valence of affect, and motivated attention for the ex-partner. Participants who were upset about a romantic break-up performed these regulation strategies before passively viewing a picture of their ex-partner, during which their electroencephalogram was recorded. Negative reappraisal decreased love feelings and made participants feel more unpleasant. Love reappraisal did not change how in love or pleasant/unpleasant participants felt. Distraction did not change love feelings but made participants feel more pleasant. This suggests that in the context of a romantic break-up, negative reappraisal is an effective love down-regulation strategy, whereas distraction is an effective positive emotion up-regulation strategy. Furthermore, all three strategies decreased motivated attention for the ex-partner, as indicated by a reduced amplitude of the late positive potential. This reduced motivated attention for the ex-partner could make it easier to deal with encounters of (reminders of) the ex-partner. Love regulation is a promising phenomenon with important everyday life and clinical implications. (PsycINFO Database Record

Aging diminishes lamellar and woven bone formation induced by tibial compression in adult C57BL/6.

Aging purportedly diminishes the ability of the skeleton to respond to mechanical loading, but recent data show that old age did not impair loading-induced accrual of bone in BALB/c mice. Here, we hypothesized that aging limits the response of the tibia to axial compression over a range of adult ages in the commonly used C57BL/6. We subjected the right tibia of old (22 month), middle-aged (12 month) and young-adult (5 month) female C57BL/6 mice to peak periosteal strains (measured near the mid-diaphysis) of -2200 µÎµ and -3000 µÎµ (n=12-15/age/strain) via axial tibial compression (4 Hz, 1200 cycles/day, 5 days/week, 2 weeks). The left tibia served as a non-loaded, contralateral control. In mice of every age, tibial compression that engendered a peak strain of -2200 µÎµ did not alter cortical bone volume but loading to a peak strain of -3000 µÎµ increased cortical bone volume due in part to woven bone formation. Both loading magnitudes increased total volume, medullary volume and periosteal bone formation parameters (MS/BS, BFR/BS) near the cortical midshaft. Compared to the increase in total volume and bone formation parameters of 5-month mice, increases were less in 12- and 22-month mice by 45-63%. Moreover, woven bone incidence was greatest in 5-month mice. Similarly, tibial loading at -3000 µÎµ increased trabecular BV/TV of 5-month mice by 18% (from 0.085 mm3/mm3), but trabecular BV/TV did not change in 12- or 22-month mice, perhaps due to low initial BV/TV (0.032 and 0.038 mm3/mm3, respectively). In conclusion, these data show that while young-adult C57BL/6 mice had greater periosteal bone formation following loading than middle-aged or old mice, aging did not eliminate the ability of the tibia to accrue cortical bone.

Adaptation of tibial structure and strength to axial compression depends on loading history in both C57BL/6 and BALB/c mice.

Tibial compression can increase murine bone mass. However, loading protocols and mouse strains differ between studies, which may contribute to conflicting results. We hypothesized that bone accrual is influenced more by loading history than by mouse strain or animal handling. The right tibiae of 4-month-old C57BL/6 and BALB/c mice were subjected to axial compression (10 N, 3 days/week, 6 weeks). Left tibiae served as contralateral controls to calculate relative changes: (loaded - control)/control. The WashU protocol applied 60 cycles/day, at 2 Hz, with a 10-s rest-insertion between cycles; the Cornell/HSS protocol applied 1,200 cycles/day, at 6.7 Hz, with a 0.1-s rest-insertion. Because sham loading, sedation, and transportation did not affect tibial morphology, unhandled mice served as age-matched controls (AC). Both loading protocols were anabolic for cortical bone, but Cornell/HSS loading elicited a more rapid response that was greater than WashU loading by 13 %. By 6 weeks, cortical bone volume of each loading group was greater than of AC (average + 16 %) and not different from each other. Ultimate displacement and energy to fracture were greater in tibiae loaded by either protocol, and ultimate force was greater with Cornell/HSS loading. At 6 weeks, independent of mouse strain, the WashU protocol produced minimal trabecular bone and the trabecular bone volume fraction of Cornell/HSS tibiae was greater than that of AC by 65 % and that of WashU by 44 %. We concluded that tibial adaptation to loading was more influenced by waveform than mouse strain or animal handling and therefore may have targeted similar osteogenic mechanisms in C57BL/6 and BALB/c mice.