A phase IIa, nonrandomized study of radium-223 dichloride in advanced breast cancer patients with bone-dominant disease

Radium-223 dichloride (radium-223) mimics calcium and emits high-energy, short-range alpha-particles resulting in an antitumor effect on bone metastases. This open-label, phase IIa nonrandomized study investigated safety and short-term efficacy of radium-223 in breast cancer patients with bone-dominant disease. Twenty-three advanced breast cancer patients with progressive bone-dominant disease, and no longer candidates for further endocrine therapy, were to receive radium-223 (50 kBq/kg IV) every 4 weeks for 4 cycles. The coprimary end points were change in urinary N-telopeptide of type 1 (uNTX-1) and serum bone alkaline phosphatase (bALP) after 16 weeks of treatment. Exploratory end points included sequential 18F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to assess metabolic changes in osteoblastic bone metastases. Safety data were collected for all patients. Radium-223 significantly reduced uNTX-1 and bALP from baseline to end of treatment. Median uNTX-1 change was −10.1 nmol bone collagen equivalents/mmol creatinine (−32.8 %; P = 0.0124); median bALP change was −16.7 ng/mL (−42.0 %; P = 0.0045). Twenty of twenty-three patients had FDG PET/CT identifying 155 hypermetabolic osteoblastic bone lesions at baseline: 50 lesions showed metabolic decrease (≥25 % reduction of maximum standardized uptake value from baseline) after 2 radium-223 injections [32.3 % metabolic response rate (mRR) at week 9], persisting after the treatment period (41.5 % mRR at week 17). Radium-223 was safe and well tolerated. Radium-223 targets areas of increased bone metabolism and shows biological activity in advanced breast cancer patients with bone-dominant disease

18F-fluorodeoxyglucose positron emission tomography-positive sarcoidosis after chemoradiotherapy for Hodgkin’s disease: a case report

<p>Abstract</p> <p>Introduction</p> <p>The occurrence of granulomatous disease in the setting of Hodgkin's disease is rare; however, when it occurs it can pose significant clinical and diagnostic challenges for physicians treating these patients.</p> <p>Case presentation</p> <p>We report the case of a 33-year-old Caucasian woman of Mediterranean descent with newly diagnosed ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET)/computed tomography (CT) scan-positive, early-stage Hodgkin's disease involving the cervical nodes who, despite having an excellent clinical response to chemotherapy, had a persistent ¹⁸F-FDG PET scan-positive study, which was suggestive of residual or progressive disease. A subsequent biopsy of her post-chemotherapy PET-positive nodes demonstrated sarcoidosis with no evidence of Hodgkin's disease.</p> <p>Conclusion</p> <p>This case highlights the fact that abnormalities observed on posttherapy PET/CT scans in patients with Hodgkin's disease are not always due to residual or progressive disease. An association between Hodgkin's disease and/or its treatment with an increased incidence of granulomatous disease appears to exist. Certain patterns of ¹⁸F-FDG uptake observed on PET/CT scans may suggest other pathologies, such as granulomatous inflammation, and because of the significant differences in prognosis and management, clinicians should maintain a low threshold of confidence for basing their diagnosis on histopathological evaluations when PET/CT results appear to be incongruent with the patient's clinical response.</p

CLRM-14. OPEN-LABEL, MULTINATIONAL, MULTICENTER, PHASE 3B/4 STUDY OF TRASTUZUMAB DERUXTECAN (T-DXD) IN PATIENTS WITH OR WITHOUT BASELINE BRAIN METASTASIS (BM) WITH PREVIOUSLY TREATED ADVANCED/METASTATIC HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2–POSITIVE BREAST CANCER (HER2+ BC): DESTINY-BREAST12

Abstract BACKGROUND Despite treatment advances, up to 50% of patients with advanced HER2+ BC develop BM (Zimmer. Cancer Rep. 2020). Patients with HER2+ BC with BM have a worse prognosis than patients without BM. In DESTINY-Breast01, T-DXd demonstrated efficacy in the overall population and preliminary efficacy in a subgroup with stable BM, with a confirmed objective response rate (ORR) of 61.4% and an extracranial confirmed ORR by independent central review (ICR) of 58.3%, median progression-free survival (PFS) of 19.4 and 18.1 mo, and median duration of response (DOR) of 20.8 and 16.9 mo (Modi. Cancer Res. 2021; Jerusalem. Ann Oncol. 2020). Here we describe a trial evaluating T-DXd in patients with previously treated advanced/metastatic HER2+ BC ±BM. DESIGN DESTINY-Breast12 (NCT04739761) is an open-label, multicenter, international (86 sites in the US, Europe, Australia, and Japan), phase 3b/4 study assessing T-DXd 5.4 mg/kg q3w efficacy and safety in patients with previously treated advanced/metastatic HER2+ BC ±BM that progressed with ≥1 prior anti-HER2–based regimen and received ≤2 lines of therapy in the metastatic setting (excluding patients with prior tucatinib). Patients (n=250/cohort) will be enrolled in cohort 1 (−BM at baseline) or 2 (+BM at baseline). BM must be untreated and not needing immediate local therapy or previously treated and stable or progressing. Primary endpoints are ORR (cohort 1) and PFS (cohort 2) (both by RECIST version 1.1 per ICR). Secondary endpoints are OS, DOR, time to progression, duration of subsequent therapy, PFS2, safety, and changes in symptoms, functioning, and QOL in both cohorts; incidence of new symptomatic CNS metastasis (CNSM) in cohort 1; and ORR and CNS ORR by RECIST 1.1 per ICR, CNS PFS and DOR, and time to new CNSM in cohort 2. This is an encore; the original presentation will be at The European Society for Medical Oncology 2021

Cancer Med

Objective Several studies show that self‐perception of aging (SPA) is a significant predictor of mental and physical health. In this study, we analyze the effect of SPA on mortality in the specific context of geriatric oncology. Methods The sample constituted of 140 individuals aged 65 years and older suffering from a recent nonmetastatic cancer (breast, lung, gynecological, or hematological), followed up to 6 years. We used Cox proportional hazards model to assess the effect of SPA at baseline on mortality. It was adjusted for age, gender, educational and cognitive level, oncological information (the site and kind of cancer), number of comorbidities, and physical and mental health at baseline. Results Patients were aged 73 years at diagnosis and were more often women (85.7%). Individuals with more negative SPA were 3.62 times more likely to die than those with a more positive SPA, with control of gender, age, education and cognitive level, mental and physical health, the category (breast, lung, gynecological, or hematological), and kind (initial or recurrence) of cancer. Conclusions These findings suggest that SPA influence the mortality of older people in the particular context of oncology. Therefore, the need to change our attitudes toward aging and older people implied indirectly by these results is discussed

Ribociclib plus fulvestrant for postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer in the phase III randomized MONALEESA-3 trial: updated overall survival

Background: Ribociclib plus fulvestrant demonstrated significant progression-free survival (PFS) and overall survival (OS) benefits in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC). Here we present a new landmark in survival follow-up for a phase III cyclin-dependent kinases 4 and 6 inhibitor clinical trial in patients with ABC (median, 56.3 months). Patients and methods: This phase III, randomized, double-blind, placebo-controlled trial was conducted at 174 sites (30 countries). Patients were men and postmenopausal women (age ≥18 years) with histologically/cytologically confirmed HR+/HER2- ABC. Patients could have received ≤1 line of endocrine therapy (ET) but no chemotherapy for ABC. Patients, assigned 2:1, were stratified by the presence/absence of liver/lung metastases and previous ET. Patients received intramuscular fulvestrant (500 mg, day 1 of each 28-day cycle plus day 15 of cycle 1) with oral ribociclib (600 mg/day, 3 weeks on, 1 week off) or placebo. Efficacy analyses were by intention to treat. Safety was assessed in patients receiving ≥1 dose study treatment. OS was a secondary endpoint. MONALEESA-3 is registered with ClinicalTrials.gov (NCT02422615; no longer enrolling). Results: Between 18 June 2015 and 10 June 2016, 726 patients were randomly assigned (484, ribociclib; 242, placebo). At data cut-off (30 October 2020), median OS (mOS) was 53.7 months (ribociclib) versus 41.5 months (placebo) [hazard ratio (HR), 0.73; 95% confidence interval (CI) 0.59-0.90]. Subgroup analyses were consistent with overall population. In the first-line setting, most patients in the ribociclib arm (∼60%) lived longer than median follow-up; mOS was 51.8 months in the placebo arm (HR, 0.64; 95% CI 0.46-0.88). In the second-line setting, mOS was 39.7 months (ribociclib) versus 33.7 months (placebo) (HR, 0.78; 95% CI 0.59-1.04). No apparent drug-drug interaction between ribociclib and fulvestrant or new safety signals were observed. Conclusions: This analysis reported extended OS follow-up in MONALEESA-3. mOS was ∼12 months longer in patients with HR+/HER2- ABC treated with ribociclib plus fulvestrant compared with fulvestrant monotherapy

Effect of maternal panic disorder on mother-child interaction and relation to child anxiety and child self-efficacy

To determine whether mothers with panic disorder with or without agoraphobia interacted differently with their children than normal control mothers, 86 mothers and their adolescents (aged between 13 and 23 years) were observed during a structured play situation. Maternal as well as adolescent anxiety status was assessed according to a structured diagnostic interview. Results showed that mothers with panic disorder/agoraphobia showed more verbal control, were more criticizing and less sensitive during mother-child interaction than mothers without current mental disorders. Moreover, more conflicts were observed between mother and child dyadic interactions when the mother suffered from panic disorder. The comparison of parenting behaviors among anxious and non-anxious children did not reveal any significant differences. These findings support an association between parental over-control and rejection and maternal but not child anxiety and suggest that particularly mother anxiety status is an important determinant of parenting behavior. Finally, an association was found between children’s perceived self-efficacy, parental control and child anxiety symptoms

A Self-Consistent Model for Positronium Formation from Helium Atoms

The differential and total cross sections for electron capture by positrons from helium atoms are calculated using a first-order distorted wave theory satisfying the Coulomb boundary conditions. In this formalism a parametric potential is used to describe the electron screening in a consistent and realistic manner. The present procedure is self consistent because (i) it satisfies the correct boundary conditions and post-prior symmetry, and (ii) the potential and the electron binding energies appearing in the transition amplitude are consistent with the wave functions describing the collision system. The results are compared with the other theories and with the available experimental measurements. At the considered range of collision energies, the results agree reasonably well with recent experiments and theories. [Note: This paper will be published on volume 42 of the Brazilian Journal of Physics

Stress among UK academics : identifying who copes best?

This paper examined the levels of stress and coping strategies among UK academics. Adopting a positive psychology approach, the influence of the character strengths of hope, optimism, gratitude and self-efficacy, on stress, subjective well-being (SWB), and mental health (GHQ) was examined in 216 academics in a UK university. The study explored the relationship between coping styles and work-coping variables of sense of coherence and work locus of control and stress. No significant differences on the stress, well-being and mental health measures were found for participants' gender, whether in full-time or part-time employment and level of seniority within the university. Participants using problem-focussed coping experienced lower levels of stress while dysfunctional coping was a positive predictor of stress. Hope agency, hope pathway, gratitude, optimism and self-efficacy were the strongest positive predictors of satisfaction with life (SWL), while levels of perceived stress negatively predicted SWL. Gratitude, hope agency and self-efficacy positively predicted positive affect, while stress was a negative predictor. Gratitude, hope agency, self-efficacy and optimism were negative significant predictors of negative affect while stress was a positive predictor. Gratitude positively predicted mental health, while stress was a negative predictor and optimism was a significant moderator of the relationship between stress and mental health. Academics with higher levels of gratitude, self-efficacy, hope and optimism report lower levels of stress at work and higher levels of well-being as measured by higher life satisfaction, higher positive affect and lower negative affect. New approaches to stress management training are suggested based on these findings

Gene expression profiling may improve diagnosis in patients with carcinoma of unknown primary

Carcinomas of unknown primary (CUP) represent between 3 and 10% of malignancies. Treatment with nonspecific chemotherapy is commonly unhelpful and the median survival is between 3 and 6 months. Gene expression microarray (GEM) analysis has demonstrated that molecular signatures can aid in tumour classification and propose foster primaries. In this study, we demonstrate the clinical utility of a diagnostic gene expression profiling tool and discuss its potential implications for patient management strategies. Paraffin tumour samples from 21 cases of ‘true' CUP patients in whom standard investigation had failed to determine a primary site of malignancy were investigated using diagnostic gene profiling. The results were reviewed in the context of histology and clinical history. Classification of tumour origin using the GEM method confirmed the clinicians' suspicion in 16 out of 21 cases. There was a clinical/GEM inconsistency in 4 out of 21 patients and a pathological/GEM inconsistency in 1 patient. The improved diagnoses by the GEM method would have influenced the management in 12 out of 21 cases. Genomic profiling and cancer classification tools represent a promising analytical approach to assist with the management of CUP patients. We propose that GEM diagnosis be considered when the primary clinical algorithm has failed to provide a diagnosis