Analysis of data from the PALOMA-3 trial confirms the efficacy of palbociclib and offers alternatives for novel assessment of clinical trials.

PURPOSE: There remains a need for novel therapies for patients with metastatic breast cancer (MBC). We explore the use of a novel biomarker of survival that could potentially expedite the testing of novel therapies. METHODS: We applied a tumor regression-growth model to radiographic measurement data from 393 women with MBC enrolled in PALOMA-3 examining efficacy of palbociclib in disease that had progressed on previous endocrine therapy. 261 and 132 women were randomized to fulvestrant plus palbociclib or placebo, respectively. We estimated rates of regression (d) and growth (g) of the sensitive and resistant fractions of tumors, respectively. We compared the median g of both arms. We examined the relationship between g and progression-free and overall survival (OS). RESULTS: As in other tumors, g is a biomarker of OS. In PALOMA-3, we found significant differences in g among patients with tumors sensitive to endocrine therapy but not amongst resistant tumors, emulating clinical trial results. Subgroup analysis found favorable g values in visceral metastases treated with palbociclib. Palbociclib efficacy demonstrated by slower g values was evident early in the trial, twelve weeks after the first 28 patients had been enrolled. CONCLUSION: Values of g, estimated using data collected while a patient is enrolled in a clinical trial is an excellent biomarker of OS. Our results correlate with the survival outcomes of PALOMA-3 and argue strongly for using g as a clinical trial endpoint to help inform go/no-go decisions, improve trial efficiency, and deliver novel therapies to patients sooner.

Application of the Chinese Version of the Montreal Cognitive Assessment-Basic for Assessing Mild Cognitive Impairment in Parkinson's Disease.

Mild cognitive impairment (MCI) is a common and pivotal non-motor symptom in Parkinson's disease (PD). It is necessary to use the appropriate tools to characterize the cognitive profiles and identify the subjects at risk of MCI in clinical practice. A cohort of 207 non-demented patients with PD and 52 age- and gender-matched cognitively normal controls (NCs) underwent the Chinese Version of Montreal Cognitive Assessment-Basic (MoCA-BC) evaluation. Patients with PD also received detailed motor and non-motor evaluation by serial scales. Cognitive profiles were investigated in patients with PD-MCI, relative to patients with normal cognition (PD-NC) and cognitively NCs. In addition, differences in demography, major motor and non-motor symptoms were compared between patients with PD-MCI and PD-NC. There were 70 patients with PD-MCI, occupying 33.8% of the total patients. Patients with PD-MCI had impairment in multiple cognitive domains, especially in executive function, memory and visuospatial function on MoCA-BC, relative to cognitively NCs or PD-NC. Compared with PD-NC patients, PD-MCI patients were older (p = 0.002) and had a later onset age (p = 0.007) and higher score of the Unified Parkinson's Disease Rating Scale (UPDRS) part III (p = 0.001). The positive rate of clinical possible rapid eye movement sleep behavior disorder (cpRBD) in the PD-MCI group was significantly increased relative to the PD-NC group (p = 0.003). Multivariate logistic analysis showed that older age (OR = 1.06; p = 0.012), higher score of UPDRS-III (OR = 1.03; p = 0.018) and the presence of cpRBD (OR = 2.10; p = 0.037) were independently associated factors of MCI in patients with PD. In conclusion, executive function, memory and visuospatial function are the main impaired cognitive profiles in PD-MCI via MoCA-BC. Aging, motor severity and RBD may be independently related factors of MCI in PD.

ROLE OF MAGNETIC RESONANCE IMAGING IN THE ASSESSMENT OF ACTIVE THYROID-ASSOCIATED OPHTHALMOPATHY PATIENTS WITH LONG DISEASE DURATION.

Objective: In thyroid-associated ophthalmopathy (TAO), long disease duration is negatively correlated with the response to immunosuppression treatment. The current treatment decision-making process does not involve magnetic resonance imaging (MRI); thus, we investigated the predictive value of MRI parameters for the immunosuppressive response in active moderate to severe TAO patients with different disease durations. Methods: We retrospectively analyzed the baseline MRI parameters of active TAO patients treated with guideline-recommended weekly glucocorticoid therapy in our center. Data were stratified by the quartile of disease duration. The signal intensity ratio (SIR) of T2-weighted images was used to describe the activity of extraocular muscles (EOMs). Results: Compared to the lowest quartile of disease duration, SIR values of EOMs were significantly lower in quartile 3 (Q3) and quartile 4 (Q4). Meanwhile, the clinical activity score (CAS) curve did not change in parallel and was not correlated with the SIR curve. In the highest quartile of disease duration, nonresponders had significantly lower SIR values of the most inflamed muscle (P = .03) and the medial rectus (P = .004) than did the responders, while no such significance was observed in patients within the lower 3 quartiles. A multivariable predictive model (including CAS, TAO duration, and SIR value) was established in each quartile. The fit of the model was better than CAS with regard to prognostic prediction and showed a high positive predictive value (Model 1: 86.67%; Model 2: 92.86%) and negative predictive value (Model 1: 88.89%; Model 2: 90%) in the top quartile. Conclusion: The anterior manifestation assessed by CAS is not always consistent with retro-orbital activity in long-term TAO patients. CAS is sufficient to reflect disease activity in short-term TAO patients. The supplementation of CAS with orbital MRI would be valuable in selecting appropriate active patients with a long disease duration. Abbreviations: AUC = area under the curve; CAS = clinical activity score; EOM = extraocular muscle; FT3 = free triiodothyronine; FT4 = free thyroxine; GC = glucocorticoid; ivGC = intravenous glucocorticoids; MRI = magnetic resonance imaging; NPV = negative predictive value; PPV = positive predictive value; SIR = signal intensity ratio; TAO = thyroid-associated ophthalmopathy; TRAb = thyroid-stimulating hormone receptor antibody; TSH = thyroid-stimulating hormone.