With cardiac doses < 4 Gy, declines in LVEF were not related to tumor laterality or heart dosimetric parameters. Statistically significant LVEF decreases were mainly attributed to doxorubicin.

Amyloid β-protein (Aβ) assembly is a seminal process in Alzheimer's disease. Elucidating the mechanistic features of this process is thought to be vital for the design and targeting of therapeutic agents. Computational studies of the most pathologic form of Aβ, the 42-residue Aβ42 peptide, have suggested that hydrogen bonding involving Ser26 may be particularly important in organizing a monomer folding nucleus and in subsequent peptide assembly. To study this question, we experimentally determined structure-activity relationships among Aβ42 peptides in which Ser26 was replaced with Gly, Ala, α-aminobutryic acid (Abu), or Cys. We observed that aliphatic substitutions (Ala and Abu) produced substantially increased rates of formation of β-sheet, hydrophobic surface, and fibrils, and higher levels of cellular toxicity. Replacement of the Ser hydroxyl group with a sulfhydryl moiety (Cys) did not have these effects. Instead, this peptide behaved like native Aβ42, even though the hydropathy of Cys was similar to that of Abu and very different from that of Ser. We conclude that H bonding of Ser26 is the factor most important in its contribution to Aβ42 conformation, assembly, and subsequent toxicity.

Purpose/Objective(s): Oligometastases is hypothesized to represent a potentially curable disease. With the emergence of stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS), additional treatment options have been presented to patients with limited metastases. Studies have shown that breast cancer patients with oligometastases tend to fair better than those patients with oligometastases from other primary sites. However, no studies have been performed that examine predictors of outcomes in patients with oligometastatic breast cancer. Materials/Methods: We identified 380 patients treated at our institution with SBRT or SRS from 2010-2014. We retrospectively reviewed the records of 62 patients with metastatic breast cancer. We defined oligometastases as metastases at 5 distinct clinical sites. Oligometastases was determined by imaging and clinical documentation. Kaplan Meier curves were used to determine survival after metastases. Cox proportional hazards model was used to assess the effects of patient, tumor, and treatment characteristics as predictors of survival after metastases. Results: There were 30 patients with oligometastases and 32 patients with non-oligometastases. 60% had initial stage I, II, or III disease, while 40% had stage IV. The tumor was ER, PR, and HER-2 positive in 63%, 46%, 20% of oligometastatic patients and 66.7%, 57%, 28% of nonoligometastatic respectively. Triple negative disease was noted in 27% in both arms. 95% received chemotherapy and about 60% received hormonal therapy in both groups. 5-year survival after metastases was 79.6% for oligometastatic vs 45.7% for non-oligometastatic patients. Univariate models showed predictors of inferior survival after metastases included: absence of oligometastases [HR 3.39; 95% CI (1.28, 9.19) p Z 0.016], HER-2 negative status [HR 12.42; 95% CI (1.63, 94.56) p Z 0.015], and triple negative status [HR 3.61; 95% CI (1.43, 9.07) p Z 0.006]. On bivariate analyses, absence of oligometastases remained a significant predictor of worse survival after metastasis; in model 1, absence of oligometastases [HR 6.07; 95% CI (1.56,23.71) p Z 0.009] adjusted for HER-2 positive status [HR 17.55; 95% CI (2.13,144.84) p Z 0.008] and in model 2, absence of oligometastases [HR 5.31; 95% CI (1.54,18.31) p Z 0.008], adjusted for triple negative status [HR 3.65; 95% CI (1.43,9.29) p Z 0.007]. Conclusion: Our study showed oligometastatic breast cancer patients have improved 5-year survival after metastases compared to those with nonoligometastases. In patients with oligometastases and HER-2 positive disease or without triple negative disease, survival after metastases was superior. Further studies are needed to identify a favorable subset of patients with oligometastases that would benefit from aggressive therapy.