Subclinical Systolic Dysfunction during Chemotherapy for Breast Cancer

Abstract Background Cardiotoxicity is the main complication related to cancer therapy. Studies indicate that global longitudinal strain is an early detector of subclinical dysfunction of the left ventricle, preceding the decline in ejection fraction (EF). However, the reproducibility of such methodology has not been tested outside specialized centers. Objectives To assess the frequency of subclinical cardiotoxicity and to compare global longitudinal strain and EF measurements during the clinical course of patients undergoing chemotherapy for breast cancer. Methods This was an observational prospective study of 78 adult women who underwent serial echocardiograms (baseline and 1, 3, and 6 months after the beginning of chemotherapy), to evaluate biplane and 3D EF and global longitudinal strain. Cardiotoxicity and subclinical dysfunction were defined according to American Society of Echocardiography/European Association of Cardiovascular Imaging criteria. Statistical significance was set at p < 0.05. Results The mean age of the patients was 50.1 ± 11.48 years. The frequency of subclinical cardiotoxicity (defined by global longitudinal strain) was 14.9% after 30 days of chemotherapy, 16.7% after 3 months, and 19.7% after 6 months, compared to 4.5%, 3%, and 6.6%, respectively, when clinical cardiotoxicity was determined according to EF. The group that developed subclinical cardiotoxicity by 30 days (group A) had a higher frequency of clinical cardiotoxicity at 3 months (p=0.028) and a lower mean biplane EF after 30 days (p= 0.036) than the group that showed no evidence of subclinical cardiotoxicity (group B). Conclusion Subclinical cardiotoxicity was frequent and began early, being associated with a drop in EF during the clinical course.

Malignancy-Related Hypercalcemia in Advanced Solid Tumors: Survival Outcomes.

Purpose Malignancy-related hypercalcemia (MRH) is associated with a dismal prognosis. The widespread use of bisphosphonates (BPs), availability of more effective drugs in cancer treatment, and improvement in supportive care might have attenuated its impact. Patients and Methods To assess overall survival (OS) of patients with MRH in a contemporary setting, we conducted a retrospective analysis of 306 patients with solid cancer hospitalized for symptomatic hypercalcemia. A multivariable Cox proportional hazards regression model was performed to evaluate possible prognostic factors associated with MRH. Results All patients had serum ionized calcium > 5.5 mg/dL or total Ca > 10.5 mg/dL. Median age was 57 years, and the majority had squamous cell carcinoma (62%) and Eastern Cooperative Oncology Group performance status > 1 (96%). Head and neck was the most frequent primary site (28%). Forty-five percent had no previous chemotherapy (CT), and subsequent CT was administered to 32%. Eighty-three percent received BP with no survival gain. Median OS was 40 (95% CI, 33 to 47) days. Patients with a performance status > 2, altered mental status, C-reactive protein > 30 mg/L, albumin < 2.5 g/dL, or body mass index < 18 kg/m2 had significantly poorer survival in a univariable analysis, and longer OS was related to treatment-naive patients, subsequent CT, and breast primary site. In the multivariable analysis, subsequent CT led to a median OS improvement of 144 versus 25 days (hazard ratio, 0.24; 95% CI, 0.14 to 0.40; P < .001). Conclusion In a contemporary setting, MRH remains a marker of poor prognosis. Patients treated with CT had better survival, which suggests that appropriate treatment of selected patients might alter the course of this syndrome.

The effects of palliative chemotherapy in metastatic colorectal cancer patients with an ECOG performance status of 3 and 4.

BACKGROUND: Although chemotherapy is standard for patients with mCRC and ECOG PS of 0/1, the real benefit for patients with ECOG PS > 2 remains uncertain, because they are generally excluded from clinical trials. Our objectives were to compare the survival and safety of ECOG PS 3/4 patients who were administered chemotherapy with those who received BSC only. PATIENTS AND METHODS: We retrospectively analyzed all consecutive mCRC patients who started first-line chemotherapy at our institution in a 4-year period. A multivariable Cox regression model was used to adjust for prognostic factors and logistic regression, to identify predictive factors of Grade 3/4 toxicity. RESULTS: From June 2008 to June 2012, 240 consecutive patients were included: 100 (41.7%) had an ECOG PS of 0/1, 75 (31.3%) ECOG PS of 2, and 65 (27%) ECOG PS of 3/4. Median survival for patients treated with chemotherapy was 18.4 months for patients with ECOG PS of 0/1, 10.8 months for those with ECOG PS of 2, and 6.8 months for patients with ECOG PS of 3/4. Among those with ECOG PS of 3/4, chemotherapy use led to a nonsignificant survival gain (median, 6.8 vs. 2.3 months for BSC; P = .13). Factors significantly associated with worse survival in an adjusted analysis were right-sided tumors (hazard ratio [HR], 2.97; P = .005) and ECOG PS status (ECOG PS 2 vs. 0/1; HR, 1.67; P = .025, and ECOG PS 3/4 vs. 0/1; HR, 2.67; P < .0001). The rate of Grade ≥ 3 toxicities during the first cycle did not differ significantly across ECOG groups; likely because 40% of ECOG PS 3/4 patients received upfront dose-reduced therapy. The rates of treatment-related hospitalization were similar across all ECOG groups. All deaths were disease-associated. CONCLUSION: Our retrospective study suggests that chemotherapy might benefit selected mCRC patients with poor PS. With up-front dose reduction and close monitoring for toxicity, the risk of serious adverse events is minimized.