Biological consequences of MLC calibration errors in IMRT delivery and QA.

PURPOSE: The purpose of this work is threefold: (1) to explore biological consequences of the multileaf collimator (MLC) calibration errors in intensity modulated radiotherapy (IMRT) of prostate and head and neck cancers, (2) to determine levels of planning target volume (PTV) and normal tissue under- or overdose flagged with clinically used QA action limits, and (3) to provide biologically based input for MLC QA and IMRT QA action limits. METHODS: Ten consecutive prostate IMRT cases and ten consecutive head and neck IMRT cases were used. Systematic MLC offsets (i.e., calibration error) were introduced for each control point of the plan separately for X1 and X2 leaf banks. Offsets were from - 2 to 2 mm with a 0.5 mm increment. The modified files were imported into the planning system for forward dose recalculation. The original plan served as the reference. The generalized equivalent uniform dose (gEUD) was used as the biological index for the targets, rectum, parotid glands, brainstem, and spinal cord. Each plan was recalculated on a CT scan of a 27 cm diameter cylindrical phantom with a contoured 0.6 cc ion chamber. Dose to ion chamber and 3D gamma analysis were compared to the reference plan. QA pass criteria: (1) at least 95% of voxels with a dose cutoff of 50% of maximum dose have to pass at 3 mm/3% and (2) dose to chamber within 2% of the reference dose. RESULTS: For prostate cases, differences in PTV and rectum gEUD greater than 2% were identified. However, a larger proportion of plans leading to greater than 2% difference in prostate PTV gEUD passed the ion chamber QA but not 3D gamma QA. A similar trend was found for the rectum gEUD. For head and neck IMRT, the QA pass criteria flagged plans leading to greater than 4% differences in PTV gEUD and greater than 5% differences in the maximum dose to brainstem. If pass criteria were relaxed to 90% for gamma and 3% for ion chamber QA, plans leading to a 5% difference in PTV gEUD and a 5%-8% difference in brainstem maximum dose would likely pass IMRT QA. A larger proportion of head and neck plans with greater than 2% PTV gEUD difference passed 3D gamma QA compared to ion chamber QA. CONCLUSIONS: For low modulation plans, there is a better chance to catch MLC calibration errors with 3D gamma QA rather than ion chamber QA. Conversely, for high modulation plans, there is a better chance to catch MLC calibration errors with ion chamber QA rather than with 3D gamma QA. Ion chamber and 3D gamma analysis IMRT QA can detect greater than 2% change in gEUD for PTVs and critical structures for low modulation treatment plans. For high modulation treatment plans, ion chamber and 3D gamma analysis can detect greater than 2% change in gEUD for PTVs and a 5% change in critical structure gEUD since either QA methods passes the QA criteria. For gEUD changes less than those listed above, either QA method has the same proportion of passing rate.

Reproductive Hormone Concentrations and Associated Anatomical Responses: Does Soy Formula Affect Minipuberty in Boys?

CONTEXT: Soy formula feeding is common in infancy and is a source of high exposure to phytoestrogens, documented to influence vaginal cytology in female infants. Its influence on minipuberty in males has not been established. OBJECTIVE: To assess the association between infant feeding practice and longitudinally measured reproductive hormones and hormone-responsive tissues in infant boys. METHODS: The Infant Feeding and Early Development study was a prospective cohort of maternal-infant dyads requiring exclusive soy formula, cow milk formula, or breast milk feeding during study follow-up. In the 147 infant boy participants, serum testosterone, luteinizing hormone, stretched penile length, anogenital distance, and testis volume were longitudinally assessed from birth to 28 weeks. We examined feeding-group differences in age trajectories for these outcomes using mixed-effects regression splines. RESULTS: Median serum testosterone was at pubertal levels at 2 weeks (176 ng/dL [quartiles: 124, 232]) and remained in this range until 12 weeks in all feeding groups. We did not observe differences in trajectories of hormone concentrations or anatomical measures between boys fed soy formula (n = 55) and boys fed cow milk formula (n = 54). Compared with breastfed boys (n = 38), soy formula-fed boys had a more rapid increase in penile length (P = .004) and slower initial lengthening of anogenital distance (P = .03), but no differences in hormone trajectories. CONCLUSION: Reproductive hormone concentrations and anatomical responses followed similar trajectories in soy and cow milk formula-fed infant boys. Our findings suggest that these measures of early male reproductive development do not respond to phytoestrogen exposure during infancy.

Comparison of Rapid to Standard Volumetric Modulated Arc Therapy for Palliative Radiotherapy in Lung Cancer Patients.

Patients with incurable lung cancer often present with debilitating symptoms that require urgent palliative radiotherapy. Volumetric modulated arc therapy (VMAT) provides several dosimetric advantages compared to basic non-conformal techniques, but involves complex planning resulting in a slower turn-around time for treatment. A simplified planning technique known as 'rapid VMAT' was developed with an aim to deliver palliative treatment to patients within 48 hours. The purpose of this study was to prospectively compare the dosimetric quality of rapid VMAT plans to standard VMAT plans. Fourteen consecutive rapid VMAT cases were re-planned de novo as per standard VMAT planning guidelines. Planning target volume (PTV) and organs at risk (OARs) were then compared. PTV coverage and dose to OARs including the spinal canal, lung, heart, and esophagus were similar between rapid and standard VMAT. Each plan was ready for treatment within 48 hours of the CT simulation. This study describes an expedited process for which palliative radiotherapy can be delivered to lung tumors with a similar robust quality that is provided for curative intent VMAT radiotherapy plans.

A Longitudinal Study of Estrogen-Responsive Tissues and Hormone Concentrations in Infants Fed Soy Formula.

Purpose: Chemicals with hormonelike activity, such as estrogenic isoflavones, may perturb human development. Infants exclusively fed soy-based formula are highly exposed to isoflavones, but their physiologic responses remain uncharacterized. Estrogen-responsive postnatal development was compared in infants exclusively fed soy formula, cow-milk formula, and breast milk. Methods: We enrolled 410 infants born in Philadelphia-area hospitals between 2010 and 2014; 283 were exclusively fed soy formula (n = 102), cow-milk formula (n = 111), or breast milk (n = 70) throughout the study (birth to 28 or 36 weeks for boys and girls, respectively). We repeatedly measured maturation index (MI) in vaginal and urethral epithelial cells using standard cytological methods, uterine volume and breast-bud diameter using ultrasound, and serum estradiol and follicle-stimulating hormone levels. We estimated MI, organ-growth, and hormone trajectories by diet using mixed-effects regression splines. Results: Maternal demographics did not differ between cow-milk-fed and soy-fed infants but did differ between formula-fed and breastfed infants. Vaginal-cell MI trended higher (P = 0.01) and uterine volume decreased more slowly (P = 0.01) in soy-fed girls compared with cow-milk-fed girls; however, their trajectories of breast-bud diameter and hormone concentrations did not differ. We observed no significant differences between boys fed cow-milk vs soy formula; estradiol was not detectable. Breastfed infants differed from soy-formula-fed infants in vaginal-cell MI, uterine volume, and girls' estradiol and boys' breast-bud diameter trajectories. Conclusions: Relative to girls fed cow-milk formula, those fed soy formula demonstrated tissue- and organ-level developmental trajectories consistent with response to exogenous estrogen exposure. Studies are needed to further evaluate the effects of soy on child development.

Tracking Medicaid managed care in rural communities: a fifty-state follow-up.

This study updates a 1997 study examining implementation of rural Medicaid managed care programs. Most states operate Medicaid managed care programs for their beneficiaries, but the types of programs vary across urban and rural settings. Over the past four years the number of rural counties covered by Medicaid managed care, including fully capitated programs, has grown, although primary care case management (PCCM) remains the predominant program type in rural areas. Health plan withdrawals from rural areas have led some states with rural capitated programs to provide financial incentives or develop alternative approaches, such as enhanced PCCM programs.

Volumetric modulated arc therapy for delivery of prostate radiotherapy: comparison with intensity-modulated radiotherapy and three-dimensional conformal radiotherapy.

PURPOSE: Volumetric modulated arc therapy (VMAT) is a novel form of intensity-modulated radiotherapy (IMRT) optimization that allows the radiation dose to be delivered in a single gantry rotation of up to 360 degrees , using either a constant dose rate (cdr-VMAT) or variable dose rate (vdr-VMAT) during rotation. The goal of this study was to compare VMAT prostate RT plans with three-dimensional conformal RT (3D-CRT) and IMRT plans. PATIENTS AND METHODS: The 3D-CRT, five-field IMRT, cdr-VMAT, and vdr-VMAT RT plans were created for 10 computed tomography data sets from patients undergoing RT for prostate cancer. The parameters evaluated included the doses to organs at risk, equivalent uniform doses, dose homogeneity and conformality, and monitor units required for delivery of a 2-Gy fraction. RESULTS: The IMRT and both VMAT techniques resulted in lower doses to normal critical structures than 3D-CRT plans for nearly all dosimetric endpoints analyzed. The lowest doses to organs at risk and most favorable equivalent uniform doses were achieved with vdr-VMAT, which was significantly better than IMRT for the rectal and femoral head dosimetric endpoints (p < 0.05) and significantly better than cdr-VMAT for most bladder and rectal endpoints (p < 0.05). The vdr-VMAT and cdr-VMAT plans required fewer monitor units than did the IMRT plans (relative reduction of 42% and 38%, respectively; p = 0.005) but more than for the 3D-CRT plans (p = 0.005). CONCLUSION: The IMRT and VMAT techniques achieved highly conformal treatment plans. The vdr-VMAT technique resulted in more favorable dose distributions than the IMRT or cdr-VMAT techniques, and reduced the monitor units required compared with IMRT.