Francisco Luís Pimentel

Background: When companies are uncertain about the potential of a new formulation to be bioequivalent to a Reference product, it is common practice to carry out downsized pilot studies as a gatekeeping in vivo strategy to decide whether to move forward or not with a full-size pivotal study. However, due to the small study size, these studies are inarguably more sensitive to variability. Objectives: To address and mitigate the uncertainty of the conclusions of pilot studies concerning the maximum observed concentration (C_max), the f₂ factor was proposed as an alternative approach to the average bioequivalence statistical methodology. Methods: In this work, the alternative methodology is applied to pharmacokinetic data from pilot bioequivalence trials performed with pazopanib 200 mg and 400 mg. Results: Despite the small sample size, and very high intra-subject variability, the f₂ factor demonstrated the potential for predicting bioequivalence. The positive results were confirmed in the full sized pivotal studies. Conclusions: In conclusion, this alternate methodology shows promise in reducing uncertainty associated with pilot studies and aiding in decisions to go forward with pivotal bioequivalence studies.

Background/Objectives: Population aging is a worldwide phenomenon and is often associated with multimorbidity and polypharmacy. Complex medication regimens are common among older adults and contribute to the occurrence of harmful health outcomes. Age is one of the main risk factors for cancer. This study aimed to determine and characterize the therapeutic complexity in older patients with cancer, and analyze the factors associated with high complexity and the impact of the oncological context. Methods: A cross-sectional study with patients aged ≥65 years with cancer was conducted in three hospitals in northern Portugal. Data collection was obtained using self-reports. The medication regimen complexity was assessed using the Medication Regimen Complexity Index (MRCI). Descriptive and association statistical analysis were performed. Logistic, linear, simple and multiple regression analysis were conducted, with and without automatic variable selection. Results: A total of 552 patients were included (median age, 71; IQR, 68–76). The mean MRCI before the oncological context was 18.67 (SD 12.60) and 27.39 (SD 16.67) after the oncological context, presenting a statistically significant difference in the values obtained (p < 0.001). An elevated complexity was significantly associated with polypharmacy, chronic diseases and with the administration of high-risk medications (p < 0.05). High MRCI values showed a relationship with the occurrence of potential drug interactions (p < 0.001). There was no relationship with the existence of cardiac risk comorbidity. Conclusions: This study demonstrated the existence of high therapeutic complexity in older patients with cancer, suggesting the need for intervention to prevent medication-related problems in this vulnerable population.

O projeto NEWAYS − Cancer Network for Welfare Aging pretendeu criar uma consciência nacional para o problema da Oncologia Geriátrica em Portugal. Para isso, propôs-se definir estratégias de atuação em quatro áreas preponderantes dos cuidados ao doente idoso com cancro, que fomentassem a sua otimização e promovessem o desenvolvimento de políticas em Oncologia Geriátrica em Portugal: clínica, economia e políticas de saúde, investigação epidemiológica e social e outras áreas de atuação (literacia em saúde, tecnologias de informação para os doentes, questões éticas, patient advocacy e awareness). Após um consenso alargado entre os especialistas que constituíram a network que alavancou este projeto, apresentam- se agora as linhas de atuação propostas.

Background: There is currently a lack of consensus on how health-related quality of life and other patient-reported outcome measures in cancer randomized clinical trials are analyzed and interpreted. This makes it difficult to compare results across randomized controlled trials (RCTs) synthesize scientific research, and use that evidence to inform product labeling, clinical guidelines, and health policy. The Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data for Cancer Clinical Trials (SISAQOL) Consortium aims to develop guidelines and recommendations to standardize analyses of patient-reported outcome data in cancer RCTs. Methods and Results: Members from the SISAQOL Consortium met in January 2017 to discuss relevant issues. Data from systematic reviews of the current state of published research in patient-reported outcomes in cancer RCTs indicated a lack of clear reporting of research hypothesis and analytic strategies, and inconsistency in definitions of terms, including “missing data,”“health-related quality of life,” and “patient-reported outcome.” Based on the meeting proceedings, the Consortium will focus on three key priorities in the coming year: developing a taxonomy of research objectives, identifying appropriate statistical methods to analyze patient-reported outcome data, and determining best practices to evaluate and deal with missing data. Conclusion: The quality of the Consortium guidelines and recommendations are informed and enhanced by the broad Consortium membership which includes regulators, patients, clinicians, and academics.

We present the case of a patient with history of colon cancer, referred for the evaluation of indeterminate pulmonary nodules by 18F-FDG PET/CT. A dual–time point protocol was performed, and images were reconstructed using VUE Point HD and a Bayesian-penalized likelihood reconstruction algorithm (Q.Clear). Visually, the quality of the images was considered better when Q.Clear was used with β value of 200, uptake in the smallest nodule (7 mm) was clearly visible only with Q.Clear reconstruction, and uptake in the smaller nodules was best defined in the delayed time point acquisition. Quantitative parameters were also higher for Q.Clear.

The ⁶⁸ Ga-prostate-specific membrane antigen ( ⁶⁸ Ga-PSMA) has been recently developed to be used, as a ligand, in positron emission tomography/computed tomography (PET/CT) prostate cancer imaging, to detect prostate disease. The main objective of this review was to collect data and findings from other studies and articles to assess, theoretically, if ⁶⁸ GA-PSMA PET/CT is a more appropriate prostate cancer diagnostic technique in comparison with others available such as CT, ¹⁸ F-fluoro-2-deoxyglucose PET/CT, or ¹⁸ F-fluoromethylcholine ( ¹⁸ F-choline) PET/CT. For that purpose, PubMed, the online scientific articles' database, was consulted where the keywords "PSMA" and "PET" were used to find relevant articles. The clinicaltrials.gov, clinical trials' database, was also consulted where the keywords " ⁶⁸ Ga-PSMA" and "prostate" were used to search clinical trials. Based on the reviewed scientific literature, several studies were conducted to assess and compare the ⁶⁸ Ga-PSMA PET/CT detection rate in prostate cancer with other available techniques. One of those studies, conducted by Giesel et al., concluded, within study sample, that 75% of patients with lymph nodes detected by ⁶⁸ Ga-PSMA PET/CT would have not been identified using other conventional morphological criteria based techniques. In Eiber et al.'s study, ⁶⁸ Ga-PSMA PET detected prostatic disease findings in 67% of patients with prostate-specific antigen levels et al.'s study, ⁶⁸ Ga-PSMA identified positive prostatic disease in 43.8% of the patients with negative findings in F-choline PET/CT. Findings from this review demonstrate that ⁶⁸ Ga-PSMA PET/C is more effective in detecting metastases, lymph nodes, and recurrent prostate cancer when compared to ¹⁸ F-choline-based PET/CT and CT. ⁶⁸ Ga-PSMA PET/CT presents also more imaging contrast and can be more cost-effective. ⁶⁸ Ga-PSMA has already been subjected to first-in-human trials, and it is now being tested in Phase II and III trials.

Neways: Cancer Network for Welfare Aging