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.

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.