The question of involvement of glucocorticoid hormones as temporal signals for the synchronization of the timekeeping system was addressed in rats with different corticosterone status. The authors showed that adrenalectomy had no effects on the synchronization of wheel-running activity rhythms to a steady-state LD 12:12 cycle, regardless of whether it was compensated for by a corticosterone replacement therapy that either reinstated constant plasma concentrations of the hormone or mimicked its natural rhythm. However, after a 12-h phase shift (daylight reversal), the lack of circulating corticosterone induced a significant shortening of the resynchronization rate (less than 3 days vs. 7 days). Normalization required restoration of a rhythmic corticosterone secretion that was synchronized to the new photoperiod. Under constant darkness, the corticosterone rhythm did not show any synchronizing effect, providing evidence that it participates in entrainment of the locomotor activity rhythm through modulation of light effects. It is proposed that, under stable lighting conditions, circulating glucocorticoids contribute to stabilizing activity rhythms by reinforcing resistance of the circadian timing system to variations of the photoperiod. Experimental evidence that serotonergic neurons are involved in relaying their modulatory effects to the clock is also presented.

IntroductionThe purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC).Material and methodsThis retrospective study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models.ResultsMedian follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ΔTLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8–18, p = 0.002) and for patients with ΔTLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5–9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ΔSUVmax. Patients with MTV2> 23cc and ΔSUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1–15.4, p< 0.01).ConclusionPost-induction FDG PET might be an added value to assess the patients’ prognosis in inoperable stage II/III NSCLC. TLG, ΔTLG as well as the association of MTV and ΔSUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.

ObjectivesTo propose an easily applicable segmentation method (perPET-RT) for delineation of tumour volume during radiotherapy on interim fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with non-small cell lung cancer (NSCLC).Material and methodsSixty-seven patients (51 primary tumours, 60 lymph nodes), from 4 prospective studies, underwent an FDG PET/CT scan during the fifth week of radiation therapy, using different generations of PET/CT. Per-therapeutic PET/CT scans were delineated in consensus by two experienced physicians leading to the gold standard threshold to be applied. The mathematical expression of Thopt, the optimal threshold to be applied as a function of the maximum standard uptake value (SUVmax), was determined. The performance of this method (perPET-RT) was assessed by computing the DICE similarity coefficient (DSC) and was compared with 8 fixed threshold values and 3 adaptive thresholding methods.ResultsThopt verified the following expression: Thopt = A.ln(1/SUVmax) + B where A and B were 2 constants. A and B were independent from the generation of PET/CT, but depended on the type of lesions (primary lung tumours vs. lymph nodes). PerPET-RT showed good to very good agreement in comparison to the gold standard. The mean and standard deviation of DSC value was 0.81 ± 0.13 for lung lesions and 0.78 ± 0.15 for lymph nodes. PerPET-RT showed a significant better agreement than the other segmentation methods (p < 0.001), except for one of the adaptive thresholding method ADT (p = 0.11).ConclusionOn the database used, perPET-RT has proven its reliability and accuracy for tumour delineation on per-therapeutic FDG PET/CT using only SUVmax measurement. This method may be used to delineate tumour volume for dose-escalation planning.Trial registrationNCT01261598, NCT01261585, NCT01576796.

No abstract

No abstract