Multi-omic molecular profiling guide's efficacious treatment selection in refractory metastatic breast cancer: a prospective phase II clinical trial.

This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi-omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA-Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP-selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow-up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11-22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan-based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan-based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease.

Utility of routine left ventricular ejection fraction measurement before anthracycline-based chemotherapy in patients with diffuse large B-cell lymphoma.

PURPOSE: Despite the lack of evidence, routine left ventricular ejection fraction (LVEF) measurement in diffuse large B-cell lymphoma (DLBCL) before anthracycline-based chemotherapy (ABC) is recommended by practice guidelines and required in DLBCL trials in the United States. METHODS: We determined the frequency of the following in 197 consecutive patients with newly diagnosed DLBCL treated at our institution: one, LVEF measurement before ABC; two, finding of asymptomatic LV dysfunction (ALVD); and three, modification in treatment strategy as a result of LVEF measurement. RESULTS: The median age was 71 years, and 54% of patients were men. LVEF was measured in 128 patients (65%) pretreatment, including in 15 with prior congestive heart failure (CHF). The reasons for not measuring LVEF were: clinically low risk for ALVD (n = 32), medical frailty (n = 15), palliative care (n = 3), ABC not standard therapy (n = 12), and prior CHF (n = 7). Among patients without prior CHF who had LVEF assessed (n = 113), ALVD was detected in four (4%), with LVEF ranging from 41% to 48%. Four patients were not treated despite normal LVEF because of comorbidities and anticipated toxicities. In contrast, all four patients with ALVD received ABC. No patient had a modification in treatment strategy as a result of LVEF measurement. After a median follow-up of 60 months, among those who remained alive, CHF developed in 15% versus 6% of patients receiving ABC who did and did not have LVEF measured, respectively (P = .246). CONCLUSION: Our findings challenge the utility of routine LVEF measurement in patients with DLBCL before ABC. Potential cost savings to our health care system could be substantial.

Contralateral testicular relapse after prophylactic radiation in a patient with primary testicular diffuse large B-cell lymphoma.

Prophylactic radiation to the contralateral uninvolved testicle has become a standard practice in the treatment of primary testicular lymphoma. While it is generally felt to be very effective, its failure rate is unknown. We describe a patient with primary testicular diffuse large B-cell lymphoma, who developed recurrent disease in the contralateral testicle despite receiving prophylactic testicular radiation, central nervous system prophylaxis, and anthracycline-based chemo-immunotherapy. Review of the literature shows that the testicular failure rate after prophylactic radiation may be unexpectedly high at 10% or more. We put forward hypotheses on testicular relapse and discuss potential alternative preventive strategies.