Sotorasib Shows Intracranial Activity in Patients with KRAS G12C-Mutated Adenocarcinoma of the Lung and Untreated Active Brain Metastases.

Treatment with sotorasib has shown intracranial complete responses and continued intracranial stabilization in KRAS G12C-mutated non-small-cell lung carcinoma (NSCLC) patients with previously treated, stable brain metastases in a post hoc analysis of the ongoing CodeBreaK 100 trial. We present the case of a patient with KRAS G12C-mutant adenocarcinoma of the lung with active untreated brain metastases with a nearly complete intracranial response only 6 weeks after start of sotorasib illustrating the benefit of sotorasib in patients with active, previously untreated brain metastases in KRAS G12C-mutated NSCLC

Patient satisfaction with divided anesthesia care.

BACKGROUND Up to now, no prospective cohort study using a validated questionnaire has assessed patients' expectation and perception of divided anesthesia care and its influence on patient satisfaction. OBJECTIVE We assessed patient satisfaction with divided anesthesia care in a district general hospital in Switzerland. We hypothesized that patient expectations, combined with their perceptions of the (un)importance of continuous anesthesia care would influence patient satisfaction. MATERIAL AND METHODS A total of 484 eligible in-patients receiving anesthesia from October 2019 to February 2020 were included and received preoperative information about divided care via a brochure and face-to-face. The primary outcome was the assessment of patient satisfaction with divided anesthesia care using a validated questionnaire. In group 1 continuity of care was considered important but not performed. In group 2 continuity was ensured. In group 3 continuity was regarded as not important and was not performed. In group 4 patients could not remember or did not answer. A psychometrically developed validated questionnaire was sent to patients at home after discharge. RESULTS A total of 484 completed questionnaires (response rate 81%) were analyzed. In group 1 (n = 110) the mean total dissatisfaction score was 25% (95% confidence interval [CI] 21.8-28.1), in group 2 (n = 61) 6.8% (95% CI 4.8-8.7), in group 3 (n = 223) 12.1% (95% CI 10.7-13.4), and in group 4 (n = 90) 15% (95% CI 11-18); ANOVA: p < 0.001, η = 0.43. Of the patients 286 (59%) considered continuity of care by the same anesthetist relatively unimportant (34%) or not important at all (25%). The other 40% considered it important (22%) or very important (18%). CONCLUSION Despite receiving comprehensive preoperative information about divided anesthesia care, 40% of patients still considered continuity of care by the same anesthetist important. We recommend further research evaluating whether and how patient expectations can be modified towards the common practice of divided care and patient satisfaction can be increased

Prognostic Significance of the Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) in Patients with Myelofibrosis: A Retrospective Study.

In myelofibrosis, comorbidities (CMs) add prognostic information independently from the Dynamic International Prognostic Scoring System (DIPSS). The Myelodysplastic Syndrome-Specific Comorbidity Index (MDS-CI) offers a simple tool for CM assessment as it is calculable after having performed a careful history and physical examination, a small routine chemistry panel (including creatinine and liver enzymes) and a limited set of functional diagnostics. To assess the prognostic impact of the MDS-CI in addition to the DIPSS and the Mutation-Enhanced International Prognostic Scoring System (MIPSS)-70, we performed a retrospective chart review of 70 MF patients who had not received allogeneic stem cell transplantation (primary MF, n = 51; secondary MF, n = 19; median follow-up, 40 months) diagnosed at our institution between 2000 and 2020. Cardiac diseases (23/70) and solid tumors (12/70) were the most common CMs observed at MF diagnosis. Overall survival (OS) was significantly influenced by the MDS-CI (median OS MDS-CI low (n = 38): 101 months; MDS-CI intermediate (n = 25): 50 months; and high (n = 7): 8 months; p < 0.001). The MDS-CI added prognostic information after inclusion as a categorical variable in a multivariate model together with the dichotomized DIPSS or the dichotomized MIPSS70: MDS-CI high HR 14.64 (95% CI 4.42; 48.48), p = 0.0002, and MDS-CI intermediate HR 1.97 (95% CI 0.96; 4.03), p = 0.065, and MDS-CI high HR 19.65 (95% CI 4.71; 81.95), p < 0.001, and MDS-CI intermediate HR 1.063 (95% CI 0.65; 4.06), p = 0.2961, respectively. The analysis of our small and retrospective MF cohort suggests that the MDS-CI represents a useful tool to identify MF patients with an increased vulnerability due to comorbidities. However, analyses of larger cohorts are necessary to define the value of the MDS-CI as a prognostic tool in comparison with other comorbidity indices

Patient-reported perioperative anaesthesia-related anxiety is associated with impaired patient satisfaction: a secondary analysis from a prospective observational study in Switzerland

Abstract Perioperative anxiety is common. The relationship between anxiety and patient satisfaction with anaesthesia is still under debate. We assessed the prevalence and different causes of anaesthesia-related fears leading to perioperative anxiety and its association with patient satisfaction. A multiple-time validated, psychometrically developed questionnaire assessing the presence of anxiety, causes of fear, and different dimensions of patient satisfaction was sent to patients after discharge. The clinical data were obtained from a previous study. The sample size was calculated to recruit a minimum of 300 completed questionnaires. Statistical analyses included multivariate logistic regression models. Complete data were available for 474 of the 600 patients recruited for the study (response rate: 79%). A total of 141 patients (30%) reported anxiety regarding anaesthesia before hospital admission. The prevalence of anxiety was significantly associated with patient age ( 54 years: n = 263, prevalence = 24%; p = 0.002), female sex (female: n = 242, prevalence 39%; male: n = 223, prevalence 20%; p < 0.001), and surgical speciality (gynaecology (n = 61, prevalence = 49%), otolaryngology (n = 56, prevalence = 46%); p < 0.001). Fear of not awakening from anaesthesia (n = 44, prevalence = 32%, SD 45.8) and developing postoperative nausea or vomiting (n = 42, prevalence = 30%, SD 46.0) were the most reported anaesthesia-related causes of fear. Anxiety was associated with impaired overall patient satisfaction (mean dissatisfaction score 15%, versus 23%, SD 16.3 in the anxious group, SD 16.3, p < 0.001), especially regarding the dimensions “information and involvement in decision-making” (14% of deficits stated in the non-anxious group compared to 23% in the anxious group, p < 0.001), “respect and trust” (2% vs 6.26%, p < 0.001) and “continuity of care” (50% vs 57%, p < 0.015). Patient-reported anaesthesia-related anxiety is common and may affect important outcome parameters such as patient satisfaction. Abstract presented in e-poster format at Euroanaesthesia 2023, June 3–5, Glasgow

A Literature Review of Racial Disparities in Prostate Cancer Research

Background: Despite recent awareness of institutional racism, there are still important racial disparities in prostate cancer medical research. We investigated the historical development of research on racial disparities and bias. Methods: PubMed was searched for the term ‘prostate cancer race’ and added key terms associated with racial disparity. As an indicator of scientific interest in the topic, we analyzed whether the number of publications increased linearly as an indicator of growing interest. The linearity is expressed as R2. Results: The general search term “prostate cancer race” yielded 4507 publications. More specific search terms with ≥12 publications showing a higher scientific interest were found after 2005. The terms with the most publications when added to the general term were “genetic” (n = 1011), “PSA” (n = 995), and “detection” (n = 861). There was a linear increase in publications for “prostate cancer race” (R2 = 0.75) since 1980. Specific terms added to the general terms with a high linear increase (R2 ≥ 0.7) were “screening” (R2 = 0.82), “detection” (R2 = 0.72), “treatment access” (R2 = 0.71), and “trial underrepresentation” (R2 = 0.71). However, only a few studies have investigated its association with sexual activity. A combination with “sexual” showed 157 publications but only two years with ≥12 publications/year. Conclusion: The terms “genetic”, “PSA”, and “detection” have been the focus of recent research on racial differences in prostate cancer. We found that old stereotypes are still being mentioned but seem to find little interest in the current literature. Further research interest was found in “treatment access”. Recently, interest in socioeconomic factors has decreased

TLD-1, a novel liposomal doxorubicin, in patients with advanced solid tumors: Dose escalation and expansion part of a multicenter open-label phase I trial (SAKK 65/16).

BACKGROUND TLD-1 is a novel liposomal doxorubicin that compared favorably to conventional doxorubicin liposomal formulations in preclinical models. This phase I first-in-human study aimed to define the maximum tolerated dose (MTD), recommended phase 2 dose (RP2D), safety and preliminary activity of TLD-1 in patients with advanced solid tumors. PATIENTS AND METHODS We recruited patients with advanced solid tumors who failed standard therapy and received up to 3 prior lines of palliative systemic chemotherapy. TLD-1 was administered intravenously every 3 weeks up to a maximum of 9 cycles (6 for patients with prior anthracyclines) from a starting dose of 10 mg/m2, according to an accelerated titration design followed by a modified continual reassessment method. RESULTS 30 patients were enrolled between November 2018 and May 2021. No dose-limiting toxicities (DLT) were observed. Maximum administered dose of TLD-1 was 45 mg/m2, RP2D was defined at 40 mg/m2. Most frequent treatment-related adverse events (TRAE) of any grade included palmar-plantar erythrodysesthesia (PPE) (50% of patients), oral mucositis (50%), fatigue (30%) and skin rash (26.7%). Most common G3 TRAE included PPE in 4 patients (13.3%) and oral mucositis in 2 (6.7%). Overall objective response rate was 10% in the whole population and 23.1% among 13 patients with breast cancer; median time-to-treatment failure was 2.7 months. TLD-1 exhibit linear pharmacokinetics, with a median terminal half-life of 95 h. CONCLUSIONS The new liposomal doxorubicin formulation TLD-1 showed a favourable safety profile and antitumor activity, particularly in breast cancer. RP2D was defined at 40 mg/m2 administered every 3 weeks. (NCT03387917)