Assessment of Micronuclei Frequency in the Peripheral Blood of Adult and Pediatric Patients Receiving Fractionated Total Body Irradiation.

The cytokinesis-block micronucleus (CBMN) assay is an established method for assessing chromosome damage in human peripheral blood lymphocytes resulting from exposure to genotoxic agents such as ionizing radiation. The objective of this study was to measure cytogenetic DNA damage and hematology parameters in vivo based on MN frequency in peripheral blood lymphocytes (PBLs) from adult and pediatric leukemia patients undergoing hematopoietic stem cell transplantation preceded by total body irradiation (TBI) as part of the conditioning regimen. CBMN assay cultures were prepared from fresh blood samples collected before and at 4 and 24 h after the start of TBI, corresponding to doses of 1.25 Gy and 3.75 Gy, respectively. For both age groups, there was a significant increase in MN yields with increasing dose (p < 0.05) and dose-dependent decrease in the nuclear division index (NDI; p < 0.0001). In the pre-radiotherapy samples, there was a significantly higher NDI measured in the pediatric cohort compared to the adult due to an increase in the percentage of tri- and quadri-nucleated cells scored. Complete blood counts with differential recorded before and after TBI at the 24-h time point showed a rapid increase in neutrophil (p = 0.0001) and decrease in lymphocyte (p = 0.0006) counts, resulting in a highly elevated neutrophil-to-lymphocyte ratio (NLR) of 14.45 ± 1.85 after 3.75 Gy TBI (pre-exposure = 4.62 ± 0.49), indicating a strong systemic inflammatory response. Correlation of the hematological cell subset counts with cytogenetic damage, indicated that only the lymphocyte subset survival fraction (after TBI compared with before TBI) showed a negative correlation with increasing MN frequency from 0 to 1.25 Gy (r = -0.931; p = 0.007). Further, the data presented here indicate that the combination of CBMN assay endpoints (MN frequency and NDI values) and hematology parameters could be used to assess cytogenetic damage and early hematopoietic injury in the peripheral blood of leukemia patients, 24 h after TBI exposure.

Toxicity and outcomes of thoracic re-irradiation using stereotactic body radiation therapy (SBRT).

BACKGROUND: Patients treated for a thoracic malignancy carry a significant risk of developing other lung lesions. Locoregional control of intrathoracic recurrences is challenging due to the impact of prior therapies on normal tissues. We examined the safety and efficacy of thoracic re-irradiation using high-precision image-guided stereotactic body radiation therapy (SBRT). METHODS: Records of 39 patients with prior intra-thoracic conventionally fractionated radiation therapy (RT) who underwent SBRT for a subsequent primary, recurrent or metastatic lung tumor from 11/2004 to 7/2011 were retrospectively reviewed. RESULTS: Median dose of prior RT was 61 Gy (range 30-80 Gy). Median biologically effective prescription dose (α/ß = 10) (BED(10)) of SBRT was 70.4 Gy (range 42.6-180 Gy). With a median followup of 12.6 months among survivors, 1- and 2-year actuarial local progression-free survival (LPFS) were 77% and 64%, respectively. Median recurrence-free (RFS) and overall survival (OS) were 13.8 and 22.0 months, respectively. Patients without overlap of high-dose regions of the primary and re-irradiation plans were more likely to receive a BED(10) ≥100 Gy, which was associated with higher LPFS (hazard ratio, [HR] = 0.18, p = 0.04), RFS ([HR] = 0.31, p = 0.038) and OS ([HR] = 0.25, p = 0.014). Grade 2 and 3 pulmonary toxicity was observed in 18% and 5% of patients, respectively. Other grade 2-4 toxicities included chest wall pain in 18%, fatigue in 15% and skin toxicity in 5%. No grade 5 events occurred. CONCLUSIONS: SBRT can be safely and successfully administered to patients with prior thoracic RT. Dose reduction for cases with direct overlap of successive radiation fields results in acceptable re-treatment toxicity profile.

Can we safely avoid fasting before abortions with low-dose procedural sedation? A retrospective cohort chart review of anesthesia-related complications in 47,748 abortions.

BACKGROUND: Some licensing authorities require fasting before abortions under intravenous sedation to avoid aspiration of gastric contents. This study was conducted to estimate the incidence of anesthesia-related complications in women undergoing abortions without preprocedure fasting. STUDY DESIGN: This is a retrospective cohort chart review of patients having abortions with both fentanyl and midazolam at two urban free-standing abortion clinics with routine policy of advising women to eat a light meal before the procedure. RESULTS: There were no reports of anesthesia-related complications in the 47,748 charts reviewed from 1998 to 2010. Applying Hanley's formula for rare events that have not occurred, the upper 95% confidence interval for the true incidence of anesthesia-related complications for women having abortion under low-dose procedural sedation without fasting was estimated to be 0.00006%. CONCLUSIONS: This large retrospective cohort chart review identified no complications related to low-dose procedural sedation in over 47,000 consecutive nonfasting patients having abortions through 18 weeks' gestation. Eliminating the requirement to fast would decrease unnecessary stress and unpleasant symptoms without increase in the anesthesia-related complications for women having abortions.

Long-term outcomes in breast cancer patients undergoing immediate 2-stage expander/implant reconstruction and postmastectomy radiation.

BACKGROUND: Breast reconstruction with tissue expander (TE)/permanent implant (PI) followed by postmastectomy radiation (PMRT) is an increasingly popular treatment for breast cancer patients. The long-term rates of permanent implant removal or replacement (PIRR) and clinical outcomes in patients treated with a uniform reconstructive surgery and radiation regimen were evaluated. METHODS: Between 1996 and 2006, 1639 patients with stage II-III breast cancer received modified radical mastectomy (MRM) at Memorial Sloan-Kettering Cancer Center. A total of 751 received TE placement at the time of mastectomy. Of these, 151 patients went on to receive chemotherapy and exchange of the TE for a permanent implant, followed by PMRT. Clinical outcomes and PIRR-free rates were estimated by Kaplan-Meier methods. Cox regression model was used to examine patient, disease, and treatment characteristics associated with PIRR. RESULTS: Median follow-up was 86 months (range, 11-161 months). The 7-year PIRR-free rate was 71% (38 PIRRs in 35 patients). The 7-year rate of PI replacement was 17.1% (21), and removal was 13.3% (17). Reasons for PIRR included infection (15); implant extrusion, shift, leak, or rupture (4); patient request (1), or multifactorial (17). On univariate analysis, no factor was significantly associated with PIRR. Two patients experienced local recurrence in the chest wall, both after 7 years. The 7-year distant metastasis-free survival rate was 81% and overall survival 93%. CONCLUSIONS: Favorable 7-year PIRR rates and clinical outcomes were achieved in a sizable cohort of patients treated with homogeneous sequencing, radiation, and reconstructive surgery and lengthy follow-up. Factors predictive for high risk of PIRR were not identifiable in this population.

Prediction of in vivo radiation dose status in radiotherapy patients using ex vivo and in vivo gene expression signatures.

After a large-scale nuclear accident or an attack with an improvised nuclear device, rapid biodosimetry would be needed for triage. As a possible means to address this need, we previously defined a gene expression signature in human peripheral white blood cells irradiated ex vivo that predicts the level of radiation exposure with high accuracy. We now demonstrate this principle in vivo using blood from patients receiving total-body irradiation (TBI). Whole genome microarray analysis has identified genes responding significantly to in vivo radiation exposure in peripheral blood. A 3-nearest neighbor classifier built from the TBI patient data correctly predicted samples as exposed to 0, 1.25 or 3.75 Gy with 94% accuracy (P < 0.001) even when samples from healthy donor controls were included. The same samples were classified with 98% accuracy using a signature previously defined from ex vivo irradiation data. The samples could also be classified as exposed or not exposed with 100% accuracy. The demonstration that ex vivo irradiation is an appropriate model that can provide meaningful prediction of in vivo exposure levels, and that the signatures are robust across diverse disease states and independent sample sets, is an important advance in the application of gene expression for biodosimetry.

The effect of age in the outcome and treatment of older women with ductal carcinoma in situ.

The effect of increasing age on outcomes and type of treatment given to older women with ductal carcinoma in situ (DCIS) was assessed. 646 women ≥60 years old (654 cases) receiving surgery for DCIS at Memorial Sloan-Kettering Cancer Center between 2000 and 2007 (8 bilateral) had wide local excision (WLE; 37%), WLE plus radiotherapy (WLE+RT; 41%), or mastectomy (22%). 45%, 38%, and 16% of patients 60-69 years, 70-79 years, and ≥80 years, respectively, received WLE+RT (P<0.001) and 25%, 20%, and 13%, received mastectomy, respectively (P<0.001). Age (P<0.001), grade (P<0.001), and necrosis (P<0.01) were highly associated with treatment. Four-year local recurrence was 3.6%. Overall local recurrence differed by treatment (mastectomy, 0%; WLE, 5%; WLE+RT, 4%; P<0.00001) but not age. It is possible to identify older women with DCIS in whom the risk of recurrence is acceptably low after WLE alone. WLE alone may be a viable treatment option for select older women with DCIS.