As part of the cancer care team, UCLA Radiation Oncology is among the top departments in the nation and is ranked No. 4 in grant research funding among Radiation Oncology Departments nationwide. At UCLA Radiation Oncology, we have reinvented the model of cancer patient care to be a 360-degree approach that revolves around patients and their families. In this process we actively shepherd patients through the complexities of cancer care, coordinating each patient’s care. In addition, to ensure safety, our eam embraces a no-errors, quality-matters culture.
BACKGROUND:Cancer is frequently associated with tumor-related anemia, and many chemotherapeutic agents impair hematopoiesis, leading to impaired quality of life for affected patients. The use of erythropoiesis-stimulating agents has come under scrutiny after prospective clinical trials using recombinant erythropoietin to correct anemia reported increased incidence of thromboembolic events and cancer-related deaths. Furthermore, previous preclinical reports indicated expansion of the pool of breast cancer-initiating cells when erythropoietin was combined with ionizing radiation. METHODS:Using four established breast cancer cell lines, we test the effects of recombinant human erythropoietin and the number of breast cancer-initiating cells in vitro and in vivo and study if recombinant human erythropoietin promotes the phenotype conversion of non-tumorigenic breast cancer cells into breast cancer-initiating cells. In a prospective study, we evaluate whether elevated endogenous serum erythropoietin levels correlate with increased numbers of tumor-initiating cells in a cohort of breast cancer patients who were scheduled to undergo radiation treatment. RESULTS:Our results indicate that recombinant erythropoietin increased the number of tumor-initiating cells in established breast cancer lines in vitro. Irradiation of breast cancer xenografts caused a phenotype conversion of non-stem breast cancer cells into induced breast cancer-initiating cells. This effect coincided with re-expression of the pluripotency factors c-Myc, Sox2, and Oct4 and was enhanced by recombinant erythropoietin. Hemoglobin levels were inversely correlated with serum erythropoietin levels, and the latter were correlated with disease stage. However, tumor sections revealed a negative correlation between serum erythropoietin levels and the number of ALDH1A3-positive cells, a marker for breast cancer-initiating cells. CONCLUSIONS:We conclude that physiologically slow-rising serum erythropoietin levels in response to tumor-related or chemotherapy-induced anemia, as opposed to large doses of recombinant erythropoietin, do not increase the pool of breast cancer-initiating cells.
From whole gland to hemigland to ultra-focal high-dose-rate prostate brachytherapy: A dosimetric analysis.
To assess the magnitude of dosimetric reductions of a focal and ultra-focal high-dose-rate (HDR) prostate brachytherapy treatment strategy relative to standard whole gland (WG) treatment.HDR brachytherapy plans for five patients treated with WG HDR monotherapy were optimized to assess different treatment strategies. Plans were generated to treat the hemigland (HG), one-third gland (1/3G), and one-sixth gland (1/6G), as well as to assess treating the WG with a boost to one of those sub-volumes (WG + HG, WG + 1/3G, WG + 1/6G). Dosimetric parameters analyzed included Target D90%, V100%, V150%, Bladder (B), Rectal (R), Urethral (U) D0.1, 1 and 2cc, Urethral V75%, and the V50% to the contralateral HG. Two-tailed t tests were used for comparison of means, and p-values less than 0.05 were considered statistically significant.Target objectives (D90 > 100% and V100 > 97%) were met in all cases. Significant organs at risk dose reductions were achieved for all approaches compared with WG plans. 1/6G vs WG plans resulted in the greatest reduction in dose with a mean bladder D2cc 24.7 vs 64.8%, rectal D2cc 32.8 vs 65.3%, urethral D1cc 52.1 vs 103.8%, and V75 14.5 vs 75% (p < 0.05 for all comparisons).Significant dose reductions to organs at risk can be achieved using HDR focal brachytherapy. The magnitude of the reductions achievable with treating progressively smaller sub-volumes suggests the potential to reduce morbidity, but the clinical impact on morbidity and tumor control remain to be investigated.
Our ability to use ionizing radiation as an energy source, as a therapeutic agent, and, unfortunately, as a weapon, has evolved tremendously over the past 120 years, yet our tool box to handle the consequences of accidental and unwanted radiation exposure remains very limited. We have identified a novel group of small molecule compounds with a 4-nitrophenylsulfonamide (NPS) backbone in common that dramatically decrease mortality from the hematopoietic acute radiation syndrome (hARS). The group emerged from an in vitro high throughput screen (HTS) for inhibitors of radiation-induced apoptosis. The lead compound also mitigates against death after local abdominal irradiation and after local thoracic irradiation (LTI) in models of subacute radiation pneumonitis and late radiation fibrosis. Mitigation of hARS is through activation of radiation-induced CD11b+Ly6G+Ly6C+ immature myeloid cells. This is consistent with the notion that myeloerythroid-restricted progenitors protect against WBI-induced lethality and extends the possible involvement of the myeloid lineage in radiation effects. The lead compound was active if given to mice before or after WBI and had some anti-tumor action, suggesting that these compounds may find broader applications to cancer radiation therapy.