RESUMO
Background: Both everolimus and peptide receptor radionuclide therapy (PRRT) are approved as monotherapies for advanced neuroendocrine tumors (NETs). Research in animal models showed synergism between the two treatment modalities. This study aimed to evaluate the safety and efficacy of combining everolimus and PRRT in the treatment of unresectable NETs. Methods: Adult patients (≥18 years) with progressing and unresectable histologically confirmed grade 1-2 NETs of all origins were enrolled. Everolimus was started at a 5 mg daily dose and was increased after the initial three patients to 10 mg daily. Patients were treated concurrently with 177Lu-DOTATATE at an 8-week interval, with planned four cycles. Safety was the primary endpoint, with response rate and progression-free survival (PFS) being secondary. Results: Eleven patients were enrolled. The trial was terminated early for poor accrual. The median age was 51 years (18-64), and 4 were males. The median number of cycles of 177Lu-DOTATATE was 3, and the median cumulative dose was 300 mCi. The most frequent grade 1-2 toxicities were stomatitis (90.9%) and nausea (72.7%). Less frequent were fatigue (63.6%), anorexia, diarrhea, and skin changes (each at a 36.4% rate). Grade 3 toxicities occurred in 36% (fatigue, infection, pneumonitis, neutropenia, and stroke). No patient developed grade 4 toxicity. Treatment was stopped because of progression in three patients, and toxicity in another three patients, in addition, in four patients due to therapy interruption and in one patient who developed stroke. One patient achieved partial response, and nine had stable disease. One patient developed disease progression. At a median follow-up of 18.9 months, three died and one was lost to follow-up. The median PFS was 23.3 months. Conclusions: The combination of everolimus at a dose of 10 mg daily and 177Lu-DOTATATE appears not to be feasible. A larger trial at a lower dose of everolimus is warranted.
RESUMO
Road traffic injury (RTI) is the third leading cause of death in Saudi Arabia. Using a mobile phone when driving is associated with distracted driving, which may result in RTIs. Because of limited empirical data, we investigated the association between mobile phone use and RTI in injured patients and community controls in Riyadh. Cases were patients admitted to King Abdulaziz Medical City (KAMC) between October 2016 and March 2018 due to RTIs. During admission, mobile phone use at the time of the accident was investigated. The controls were drivers observed at various locations citywide. A logistic regression model was constructed to estimate the association between mobile phone use while driving and sustaining RTIs. We included 318 cases and 1700 controls. For the cases, using a mobile phone was associated with higher severity and prevalence of disability. In addition, using a mobile phone while driving is associated with 44% higher odds of incurring a severe RTI (p = 0.04). Mobile phone use while driving is prevalent in Riyadh and pose a significant threat of disability. In addition, the low prevalence of seatbelt use is alarming and requires significant improvement. Prevention programs may use these findings to educate the public and policymakers and to advocate for increased visibility of enforcement to reduce RTIs and improve population health.
