Clinical features and outcomes of advanced HER2+ esophageal/GEJ cancer with brain metastasis.

BACKGROUND: Brain metastasis (BRM) is uncommon in gastroesophageal cancer. As such, clinicopathologic and molecular determinants of BRM and impact on clinical outcome remain incompletely understood. METHODS: We retrospectively analyzed clinicopathologic data from advanced esophageal/gastroesophageal junction (E/GEJ) patients at Johns Hopkins from 2003 to 2021. We investigated the association between several clinical and molecular features and the occurrence of BRM, with particular focus on human epidermal growth factor receptor 2 (HER2) overexpression. Survival outcomes and time to BRM onset were also evaluated. RESULTS: We included 515 patients with advanced E/GEJ cancer. Tumors were 78.3% esophageal primary, 82.9% adenocarcinoma, 31.0% HER2 positive. Cumulative incidence of BRM in the overall cohort and within HER2+ subgroup was 13.8% and 24.3%, respectively. HER2 overexpression was associated with increased risk of BRM [odds ratio 2.45; 95% confidence interval (CI) 1.10-5.46]. On initial presentation with BRM, 50.7% had a solitary brain lesion and 11.3% were asymptomatic. HER2+ status was associated with longer median time to onset of BRM (14.0 versus 6.3 months, P < 0.01), improved median progression free survival on first-line systemic therapy (hazard ratio 0.35, 95% CI 0.16-0.80), and improved median overall survival (hazard ratio 0.20, 95% CI 0.08-0.54) in patients with BRM. CONCLUSION: HER2 overexpression identifies a gastroesophageal cancer molecular subtype that is significantly associated with increased risk of BRM, though with later onset of BRM and improved survival likely reflecting the impact of central nervous system-penetrant HER2-directed therapy. The prevalence of asymptomatic and solitary brain lesions suggests that brain surveillance for HER2+ patients warrants prospective investigation.

Introducing magnetic resonance imaging into the lung cancer radiotherapy workflow - An assessment of patient experience.

INTRODUCTION: Magnetic resonance imaging (MRI) offers superior soft tissue contrast to computed tomography (CT), the current standard imaging modality for planning radiotherapy treatment. Improved soft tissue contrast could reduce uncertainties in identifying tumour and surrounding healthy tissues, potentially leading to improved outcomes in patients with lung cancer. This study explored patient experience of MR treatment planning scans in addition to a CT scan. METHODS: Participants were recruited to the 'Magnetic Resonance Imaging for the Delineation of Organs At Risk and Target Volumes in Lung Cancer Patients (MR-Lung)' study at a UK specialist cancer centre. Participants completed their standard of care radiotherapy planning CT scan and two additional MRI scans. Baseline and post-scan questionnaires were completed assessing anxiety and claustrophobia. Motion artefact during MRI was assessed by a modified visual grading analysis. Sixteen participants completed semi-structured interviews; transcripts were analysed thematically. RESULTS: 29 people (66% female; aged 54-89 years) participated. Nineteen participants completed all imaging and 10 participants withdrew before completion. There was minimal adverse impact on state and scan-specific anxiety levels from completing the MRI scans. Completers experienced significantly less scan-specific anxiety during MRI 1 compared to non-completers (U = 33, z = -1.98, p < 0.05). 78% of those who withdrew during or post MRI 1 were positioned 'arms up'. Motion artefact negatively impacted image quality in 34% of scans. Participants commonly reported concerns during MRI; noise, claustrophobia and pain in upper limbs. CONCLUSION: Two thirds of participants tolerated two additional MR scans with minimal adverse impact on anxiety levels. IMPLICATIONS FOR PRACTICE: Patient arm positioning and comfort ought to be considered when introducing MR-Linac systems. A screening tool to identify those at high risk of non-completion should be developed.

Financial toxicity in lung cancer: an assessment of magnitude, perception, and impact on quality of life.

BACKGROUND: Advances in lung cancer therapy have resulted in improved clinical outcomes. Unfortunately, advances can come at a financial cost to patients and their families that poses a significant risk to overall quality of life (QoL). Financial distress has been shown to be associated with increased symptom burden and decreased treatment compliance but the magnitude of financial distress is not well characterized in lung cancer populations. PATIENTS AND METHODS: Patients with stage II-IV newly diagnosed lung cancer and starting first-line therapy were recruited at a tertiary academic institution between July 2018 and April 2019. The comprehensive score for financial toxicity (COST) was used to assess financial toxicity and the Functional Assessment of Cancer Therapy-Lung (FACT-L) was used to assess QoL. Associations between financial toxicity and baseline variables were assessed using multivariable linear regression and correlations were assessed using the Pearson correlation. RESULTS: In this study, 143 consecutive patients were approached and 91.6% agreed to participate (N = 131). The median age was 65 years (35-90); 52.7% were male (n = 69), and 75.6% were white (n = 99). The inability to afford basic necessities and having <1 month of savings was associated with increased financial toxicity (P < 0.001) after adjusting for other factors such as age, race, insurance, and income. There was also a trend toward increased financial toxicity among those who were employed but on sick leave (P = 0.06). Increased financial toxicity was correlated with a decrease in QoL (correlation coefficient 0.41, P < 0.001). Patients' anticipated out-of-pocket (OOP) expenses for the upcoming 6 months ranged from $0 to $50 000 (median $2150). However, there was no correlation between anticipated OOP expenses and either financial toxicity or QoL. CONCLUSIONS: These data identify key factors for identifying at-risk patients and builds a framework for exploring the benefit of financial counseling interventions, which may improve QoL and oncologic outcomes.

Tissue biomarkers for prostate cancer radiation therapy.

Prostate cancer is the most common cancer and second leading cause of cancer deaths among men in the United States. Most men have localized disease diagnosed following an elevated serum prostate specific antigen test for cancer screening purposes. Standard treatment options consist of surgery or definitive radiation therapy directed by clinical factors that are organized into risk stratification groups. Current clinical risk stratification systems are still insufficient to differentiate lethal from indolent disease. Similarly, a subset of men in poor risk groups need to be identified for more aggressive treatment and enrollment into clinical trials. Furthermore, these clinical tools are very limited in revealing information about the biologic pathways driving these different disease phenotypes and do not offer insights for novel treatments which are needed in men with poor-risk disease. We believe molecular biomarkers may serve to bridge these inadequacies of traditional clinical factors opening the door for personalized treatment approaches that would allow tailoring of treatment options to maximize therapeutic outcome. We review the current state of prognostic and predictive tissue-based molecular biomarkers which can be used to direct localized prostate cancer treatment decisions, specifically those implicated with definitive and salvage radiation therapy.

Assessing oncologic benefit in clinical trials of immunotherapy agents.

BACKGROUND: USA Food and Drug Administration approval for cancer therapy requires demonstration of patient benefit as a marker of clinical efficacy. Prolonged survival is the gold standard for demonstration of efficacy, but other end points such as antitumor response, progression-free survival, quality of life, or surrogate end points may be used. DESIGN: This study was developed based on discussion during a roundtable meeting of experts in the field of immunotherapy. RESULTS: In most clinical trials involving cytotoxic agents, response end points use RECIST based on the premise that 'effective' therapy causes tumor destruction, target lesion shrinkage, and prevention of new lesions. However, RECIST may not be appropriate in trials of immunotherapy. Like other targeted agents, immunotherapies may mediate cytostatic rather than direct cytotoxic effects, and these may be difficult to quantify with RECIST. Furthermore, significant time may elapse before clinical effects are quantifiable because of complex response pathways. Effective immunotherapy may even mediate transient lesion growth secondary to immune cell infiltration. CONCLUSIONS: RECIST may not be an optimal indicator of clinical benefit in immunotherapy trials. This article discusses alternative clinical trial designs and end points that may be more relevant for immunotherapy trials and may offer more effective prediction of survival in pivotal phase III studies.

A survival strategy for an academic psychiatry department in a managed care environment.

The changing economics of medical practice have had a profound effect on the educational, research, and service missions of academic departments of psychiatry across the country. The authors describe the development of a managed behavioral health care organization in their parent academic health system as a survival strategy for allowing their department to function in a managed care environment. They present a series of lessons learned in this effort to adapt to a highly volatile managed behavioral health care market: know how you fit into your market as well as your institution, form cooperative alliances within and outside of your institution, provide incentives to manage risk, focus on core competencies, innovate in your areas of strength, and collect data.

Weaning children from mechanical ventilation: a prospective randomized trial of protocol-directed versus physician-directed weaning.

OBJECTIVE: Compare outcomes between physician-directed and protocol-directed weaning from mechanical ventilation in pediatric patients. DESIGN: Prospective-randomized. SETTING: Pediatric and cardiac intensive care units in a 307-bed tertiary referral hospital for children. INTERVENTIONS: The control group (physician-directed) was weaned according to individual physician order for reduction in minute ventilation, positive end-expiratory pressure, and ordered oxygen saturation parameters for reduction in fraction of inspired oxygen (F(IO)(2)). The study group (protocol-directed) was weaned according to a predetermined algorithm developed for the purpose of this investigation. METHODS: The study enrolled 223 patients (116 physician-directed, 107 protocol-directed). All patients were monitored for hemodynamics, ventilator parameters, arterial blood gas values when available, oxygen saturation, weaning time, pre-weaning time, extubation time, and time on F(IO)(2) > or = 0.40. We also monitored the incidence of reintubation, subglottic stenosis, tracheitis, and pneumonia. The protocol-directed group had additional measurements of actual versus predicted minute volume, comparisons of respiratory rate (actual versus predicted for age), and presence of spontaneous breathing effort for 10 consecutive minutes. Data analysis was done according to intent to treat. RESULTS: There was no significant difference in 12-hour and 24-hour pediatric risk of mortality (PRISM III) scores between groups. The protocol-directed group overall had shorter total ventilation time, weaning time, pre-weaning time, time to extubation, and time on F(IO)(2) >0.40, although after stratification for respiratory diagnosis, only the difference in weaning time remained significant. There was no difference in the incidence of reintubation, new-onset tracheitis, subglottic stenosis, or pneumonia. CONCLUSIONS: Protocol-directed weaning resulted in a shorter weaning time than physician-directed weaning in these pediatric patients.

CNS Sjögren's syndrome: an underrecognized and underappreciated neuropsychiatric disorder.

Sjögren's syndrome is a common medical condition that may produce psychiatric symptoms. Untreated deficits can become permanent, sometimes resulting in death. The hypothesized mechanism involves CNS vasculitis. Psychoactive medications treat psychiatric symptoms but leave the underlying medical process unaffected. Laboratory tests to diagnose Sjögren's syndrome and specific treatments for this condition are improving.

The psychotic patient.

Psychotic disorders are relatively rare in the primary care setting, compared with depressive and anxiety disorders, but patient suffering is significantly higher for patients with psychotic symptoms. Primary care physicians are assuming more responsibility for the area of these patients in today's managed care environment. The practitioner needs to eliminate medical, substance, and mood origins of the psychotic symptoms before assuming a patient has a psychotic disorder (e.g., schizophrenia). This article outlines a diagnostic and treatment approach for patients with psychotic symptoms who are managed in the primary care setting.

A review of bipolar disorder among adults.

OBJECTIVE: This paper reviews the epidemiology, etiology, assessment, and management of bipolar disorder. Special attention is paid to factors that complicate treatment, including noncompliance, comorbid disorders, mixed mania, and rapid cycling. Advances in biopsychosocial treatments are briefly reviewed, including new health service models for providing care. METHODS: A MEDLINE search was done for the period from January 1988 through October 1997 using the key terms of bipolar disorder, diagnosis, and treatment. Papers selected for further review included those published in English in peer-reviewed journals. Preference was given to articles reporting randomized, controlled trials. RESULTS: Bipolar disorder is a major public health problem. The etiology of the disorder appears multifactorial. Diagnosis often occurs years after onset of the disorder. Comorbid conditions are common. Management includes a lifetime course of medication and attention to psychosocial issues for patients and their families. Standardized treatment guidelines for the management of acute mania have been developed. New potential treatments are being investigated. CONCLUSIONS: Assessment of bipolar disorder must include careful attention to comorbid disorders and predictors of compliance. Randomized trials are needed to further evaluate the efficacy of medication, psychosocial interventions, and other health service interventions, particularly as they relate to the management of acute bipolar depression, bipolar disorder co-occurring with other disorders, and maintenance prophylactic treatment.

Acute stress disorder as a predictor of posttraumatic stress symptoms.

OBJECTIVE: Using the DSM-IV diagnostic criteria for acute stress disorder, the authors examined whether the acute psychological effects of being a bystander to violence involving mass shootings in an office building predicted later posttraumatic stress symptoms. METHOD: The participants in this study were 36 employees working in an office building where a gunman shot 14 persons (eight fatally). The acute stress symptoms were assessed within 8 days of the event, and posttraumatic stress symptoms of 32 employees were assessed 7 to 10 months later. RESULTS: According to the Stanford Acute Stress Reaction Questionnaire, 12 (33%) of the employees met criteria for the diagnosis of acute stress disorder. Acute stress symptoms were found to be an excellent predictor of the subjects' posttraumatic stress symptoms 7-10 months after the traumatic event. CONCLUSIONS: These results suggest not only that being a bystander to violence is highly stressful in the short run, but that acute stress reactions to such an event further predict later posttraumatic stress symptoms.