Spirituality can improve quality of life and decrease the incidence of anxiety and depression in cancer patients. Our results highlight the need to incorporate spiritual care in healthcare systems.

Brain metastases (BM) are diagnosed frequently in non-small cell lung cancer (NSCLC) patients. Despite the high incidence of BM (up to 40% in unselected patients), patients with untreated and/or unstable BM were excluded from pivotal immune checkpoint inhibitors (ICI) NSCLC trials. Percentage of patients with stable and treated BM in these trials ranged from 9.1 to 14.7% and ICI benefit over chemotherapy was not always demonstrated. Only small trials have been completed that demonstrated ICI efficacy in locally untreated, selected BM patients. With 33%, cranial objective response rate (ORR) was comparable to extracranial ORR and responses were often durable. With the promising survival benefits of ICI, in daily practice also unstable and/or untreated BM patients will often receive treatment with ICI and extrapolating clinical trial data to these patients can be challenging. In this review, we will summarize the preclinical rationale and potential concerns for the use of ICI in BM patients. Furthermore, we will summarize BM subgroup data from the pivotal NSCLC trials, retrospective series, the NSCLC BM specific ICI trials and the use of cranial radiation and ICI. Last, we provide an overview of response measurement criteria and future directions.

Doxorubicin (DXR) incorporated into biodegradable acrylate nanoparticles such as polyisohexylcyanoacrylate (PIHCA) has been shown to increase DXR cytotoxicity and reduce cardiotoxicity by modifying tissue distribution in preclinical studies. We have conducted a phase I clinical trial of DXR-PIHCA in 21 patients with refractory solid tumors (10 male, 11 female, median age: 53 years, median PS: 1, prior free-DXR therapy: 7 patients). A total of 32 courses at 28 day intervals were administered at 6 dose levels (15, 30, 45, 60, 75 and 90 mg/m2). The drug was given as a 10 minute IV infusion on day 1 to the first 5 patients: 2 of them presented a grade 2 allergic reaction (W.H.O. criteria) during infusion, which was rapidly reversible once drug administration was discontinued. Subsequently, in the other 16 patients, the administration was modified to a 60 minute i.v. perfusion diluted in 250 cc of Dextrose 5%: only 1 patient presented the same allergic reaction. Grade 2 fever and vomiting occurred in 9 patients and 7 patients respectively during the first 24 h after treatment. There was no cardiac toxicity among the 18 evaluable patients. Grade 3 or 4 hematologic toxicity occurred at the 75 and 90 mg/m2 dose level. The dose limiting toxicity was neutropenia. The maximum tolerated dose was 90 mg/m2 and the recommended phase II dose was 75 mg/m2. A pharmacokinetic evaluation of DXR-PIHCA was conducted in 3 patients each at a different dose level (60, 60 and 75 mg/m2) and was compared with free DXR given to the same patients in the same conditions.