Early after Anth-bC, LV mass reductions associate with worsening HF symptomatology independent of LVEF. These data suggest an alternative mechanism whereby anthracyclines may contribute to HF symptomatology and raise the possibility that surveillance strategies during Anth-bC should also assess LV mass.

BackgroundSmall cell lung cancer (SCLC) is a common lung cancer which presents with extensive stage disease at time of diagnosis in two-thirds of patients. For treatment of advanced disease, traditional platinum doublet chemotherapy induces response rates up to 80% but with few durable responses. CPI-613 is a novel anti-cancer agent that selectively inhibits the altered form of mitochondrial energy metabolism in tumor cells.MethodsWe evaluated CPI-613 with a single-arm, open-label phase II study in patients with relapsed or refractory SCLC. CPI-613 was given at a dose of 3,000 mg/m2 on days 1 and 4 of weeks 1–3 of 4 week cycle. The primary outcome was response rate as assessed by CT imaging using RECIST v1.1 criteria. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and toxicity. Twelve patients were accrued (median age 57yo) who had previously received between 1 and 4 lines of chemotherapy (median 1) for SCLC with a treatment-free interval of less than 60 days in 9 of the 12 patients.ResultsNo complete or partial responses were seen. Ten patients (83%) progressed as best response and 2 (17%) were not evaluable for response. Median time to progression was 1.7 months (range 0.7 to 1.8 months). Eleven patients (92%) died with median overall survival of 4.3 months (range 1.2 to 18.2 months). The study was closed early due to lack of efficacy. Of note, three out of three patients who progressed after CPI-613 and were subsequently treated with standard topotecan then demonstrated treatment response with survival for 18.2, 7.4, and 5.1 months. We conducted laboratory studies which found synergy in-vitro for CPI-613 with topotecan.ConclusionsSingle agent CPI-613 had no efficacy in this study. Further study of CPI 613 in combination with a topoisomerase inhibitor is warranted.

High-dose glucocorticoids such as prednisone are combined with cytotoxic chemotherapy in the R-CHOP or dose adjusted R-EPOCH regimens used for non-Hodgkin lymphoma (NHL). In this retrospective study, our primary objective was to evaluate the incidence of hyperglycemia during first-line R-CHOP or DA-EPOCH-R. The secondary objectives were to evaluate the incidence of chemotherapy alteration and overall survival in those with and without hyperglycemia. One hundred and sixty patients were eligible. We found that 47% of all patients had at least one hyperglycemic episode and hyperglycemia was associated with chemotherapy alteration (p =.028). Multivariate analysis revealed international prognostic index (IPI) ≥3 (p =.045) and chemotherapy alteration (p =.001) were associated with decreased overall survival. We conclude that hyperglycemia is common during first-line NHL treatment with R-CHOP or DA-EPOCH-R, even in the absence of known diabetes and is associated with alterations of chemotherapy. Baseline pre-PET scan fasting blood glucose of 100 mg/dL or higher may predict hyperglycemia during therapy.

Background Although changes in left ventricular end‐systolic volume ( LVESV ), left ventricular end‐diastolic volume, and global circumferential strain occur during cancer treatment, the relationship of these changes to the 2‐year post–cancer‐treatment measures of left ventricular ejection fraction ( LVEF ) are unknown. Methods and Results In a prospective, continuously recruited cohort of 95 patients scheduled to receive potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or soft tissue sarcoma, measures of left ventricular end‐diastolic volume, LVESV , global circumferential strain, and LVEF were acquired via cardiac magnetic resonance imaging before and then 3 and 24 months after initiating treatment by individuals blinded to all patient identifiers. Participants had an average age of 54±15 years; 68% were women, and 82% were of white race. LVEF declined from 62±7% to 58±9% over the 24 months ( P <0.0001), with 42% of participants experiencing a >5% decline in LVEF at 24 months. Predictors of a 24‐month >5% decline in LVEF included the following factors from baseline to 3 months into treatment: (1) >3‐mL increases in LVESV ( P =0.033), (2) >3‐mL increases in LVESV or 10‐mL declines in left ventricular end‐diastolic volume with little change in LVESV ( P =0.001), or (3) ≥10% deteriorations in global circumferential strain with little change in LVESV ( P =0.036). Conclusion During receipt of potentially cardiotoxic chemotherapy, increases in LVESV , the absence of its deterioration during decreases of left ventricular end‐diastolic volume, or the deterioration of global circumferential strain without a marked decrease in LVESV help identify those who will develop more permanent 2‐year declines in LVEF .

We sought to determine the frequency by which decreases in left ventricular (LV) end-diastolic volume (LVEDV) with and without increases in end-systolic volume (LVESV) influenced early cancer treatment-associated declines in left ventricular ejection fraction (LVEF) or LV mass. One hundred and twelve consecutively recruited individuals (aged 52 ± 14 years) with cancer underwent blinded cardiovascular magnetic resonance (CMR) measures of LV volumes, mass, and LVEF before and 3 months after initiating potentially cardiotoxic chemotherapy (72 % of participants received anthracyclines). Twenty-six participants developed important declines in LVEF of >10% or to values <50% at 3 months, in whom 19% versus 60%, respectively, experienced their decline in LVEF due to isolated declines in LVEDV versus an increase in LVESV; participants who dropped their LVEF due to decreases in LVEDV lost more LV mass than those who dropped their LVEF due to an increase in LVESV (p=0.03). Nearly a fifth of individuals experience marked LVEF declines due to an isolated decline in LVEDV after initiating potentially cardiotoxic chemotherapy. Since reductions in intravascular volume (which could be treated by volume repletion) may account for LVEDV related declines in LVEF, these data indicate that LV volumes should be reviewed along with LVEF when acquiring imaging studies for cardiotoxicity during treatment for cancer.

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Background: Symptoms of psychological distress, including fear of cancer recurrence (FCR) and quality of life (QOL) deficits are common along the hematopoietic stem cell transplantation (HCT) survivorship trajectory. Identifying patterns over time could contribute to timely interventions. Materials and Methods: HCT recipients completed the Distress Thermometer (DT), the Center for Epidemiologic Studies-Depression scale (CES-D), the Fear of Relapse and Recurrence Scale, and the Functional Assessment of Cancer Therapy (FACT-BMT) at hospital admission, discharge, 3, 6, 12, and 24 months post-HCT. Demographic data and performance status (PS) were collected at baseline. Mean scores (standard deviation) and frequencies were calculated. We utilized a linear mixed model approach on the repeated measures data (outcome of FCR, with predictors of distress, depressive symptoms and QOL). A multivariate repeated measures regression was constructed to assess what variables were associated with FCR. Results: A total of 198 patients completed questionnaires at admission. A total of 144 patients were deceased or lost to follow-up at 2 years. Both CES-D (P = .006) and DT (P = .0019) scores changed significantly over time and were higher at hospital discharge. FCR did not change significantly (P = .28). QOL was most impaired at hospital discharge. FCR did not correlate with actual recurrence. A significant percentage of recipients were afraid of cancer recurrence; however, a much greater percentage did not feel that fear of recurrence got in the way of enjoying life. QOL (P < .0001) and PS (P = .014) were significant predictors of FCR. A substantial percentage of patients reported significant (>16) depressive symptoms and distress levels (≥4) during the 2-year study period. Conclusions: Depressive symptoms and distress were highest at discharge, whereas overall QOL was lowest. FCR was prominent; yet for the majority, it was not an impediment to enjoying life. A psychosocial intervention may be most useful if introduced at hospital discharge and initiated during the first 3 months following HCT when distress is high.

Although the sensitivity of EBUS-TBNA for the diagnosis of lymphoma did not reach values of published data for non-small cell lung cancer, EBUS-TBNA can be considered as a first-line diagnostic tool for patients with mediastinal and/or hilar lymphadenopathy suspected to be lymphoma. Because of the inherent limitations in small volume needle biopsies it is essential that negative samples obtained in the setting of high clinical suspicion warrant further evaluation.