Multicenter Trial of Stereotactic Body Radiation Therapy for Low- and Intermediate-Risk Prostate Cancer: Survival and Toxicity Endpoints.

PURPOSE: The radiobiology of prostate cancer may favor the extreme hypofractionation inherent in stereotactic body radiation therapy (SBRT); however, data from a large multicenter study are lacking. We therefore examined the hypothesis that dose-escalated SBRT can be safely administered across multiple institutions, with favorable 5-year disease-free survival (DFS) rates compared with historical controls. METHODS AND MATERIALS: Twenty-one centers enrolled 309 patients with prostate adenocarcinoma: 172 with low-risk (LR) and 137 with intermediate-risk (IR) disease. All were treated with a non-coplanar robotic SBRT platform using real-time tracking of implanted fiducials. The prostate was prescribed 40 Gy in 5 fractions of 8 Gy. We assessed toxicities using Common Terminology Criteria for Adverse Events (CTCAE) version 3 and biochemical failure using the "nadir + 2" definition. The study population yielded 90% power to identify excessive (>10%) rates of grade ≥3 genitourinary (GU) or gastrointestinal toxicities and, in the LR group, 80% power to show superiority in DFS over a 93% historical comparison rate. RESULTS: At a median follow-up of 61 months, 2 LR patients (1.2%) and 2 IR patients (1.5%) experienced grade 3 GU toxicities, far below the 10% toxicity rate deemed excessive (upper limits of 95% confidence interval, 3.5% and 4.3%, respectively). No grade 4 or 5 toxicities occurred. All grade 3 toxicities were GU, occurring 11 to 51 months after treatment. For the entire group, the actuarial 5-year overall survival rate was 95.6% and the DFS rate was 97.1%. The 5-year DFS rate was 97.3% for LR patients (superior to the 93% DFS rate for historical controls; P = .0008; lower limit of 95% confidence interval, 94.6%) and 97.1% for IR patients. CONCLUSIONS: Dose-escalated prostate SBRT was administered with minimal toxicity in this multi-institutional study. Relapse rates compared favorably with historical controls. SBRT is a suitable option for LR and IR prostate cancer.

Vanished Twins and Misdiagnosed Sex: A Case Report with Implications in Prenatal Counseling Using Noninvasive Cell-Free DNA Screening.

Cell-free DNA testing is a recently introduced method for screening pregnant women for fetal trisomy, which is associated with some common significant genetic diseases, as well as the sex of the fetus. The case described here demonstrates the connection between the ultrasound "vanishing twin" phenomenon and the misdiagnosis of prenatal sex using cell-free DNA testing.

US term stillbirth rates and the 39-week rule: a cause for concern?

BACKGROUND: More than a decade ago an obstetric directive called "the 39-week rule" sought to limit "elective" delivery, via labor induction or cesarean delivery, before 39 weeks 0 days of gestation. In 2010 the 39-week rule became a formal quality measure in the United States. The progressive adherence to the 39-week rule throughout the United States has caused a well-documented, progressive reduction in the proportion of term deliveries occurring during the early-term period. Because of the known association between increasing gestational age during the term period and increasing cumulative risk of stillbirth, however, there have been published concerns that the 39-week rule-by increasing the gestational age of delivery for a substantial number of pregnancies-might increase the rate of term stillbirth within the United States. Although adherence to the 39-week rule is assumed to be beneficial, its actual impact on the US rate of term stillbirth in the years since 2010 is unknown. OBJECTIVE: To determine whether the adoption of the 39-week rule was associated with an increased rate of term stillbirth in the United States. STUDY DESIGN: Sequential ecological study, based on state data, of US term deliveries that occurred during a 7-year period bounded by 2007 and 2013. The patterns of the timing of both term childbirth and term stillbirth were determined for each state and for the United States as a whole. RESULTS: A total of 46 usable datasets were obtained (45 states and the District of Columbia). During the 7-year period, there was a continuous reduction in all geographic entities in the proportion of term deliveries that occurred before 39 weeks of gestation. The overall rate of term stillbirth, when we compared 2007-2009 with 2011-2013, increased significantly (1.103/1000 vs 1.177/1000, RR 1.067, 95% confidence interval 1.038-1.096). Furthermore, during the 7-year period, the increase in the rate of US term stillbirth appeared to be continuous (estimated slope: 0.0186/1000/year, 95% confidence interval 0.002-0.035). Assuming 3.5 million term US births per year, and given 6 yearly "intervals" with this rate increase, it is possible that more than 335 additional term stillbirths occurred in the United States in 2013 as compared with 2007. In addition, during the 7-year period, there was a progressive shift in the timing of delivery from the 40th week to the 39th week. Absent this confounding factor, the magnitude of association between the adoption of the 39-week rule and the increase in rate of term stillbirth might have been greater. CONCLUSIONS: Between 2007 and 2013 in the United States, the adoption of the 39-week rule caused a progressive reduction in the proportion of term births occurring before the 39th week of gestation. During the same interval the United States experienced a significant increase in its rate of term stillbirth. This study raises the possibility that the 39-week rule may be causing unintended harm. Additional studies of the actual impact of the adoption of the 39-week rule on major childbirth outcomes are urgently needed. Pressures to enforce the 39-week rule should be reconsidered pending the findings of such studies.

Occupational health characteristics of women on dairy farms in Pennsylvania.

Women play a significant role in Pennsylvania production agriculture, thereby exposing themselves to occupational health risks. The goal of this cross-sectional study was to assess the incidence of health conditions with a possible zoonotic origin in this underserved population. A written survey was sent to a stratified, random sample of dairy farms in Pennsylvania (n = 3709) using a modified version of the Dillman method. In addition to demographic data, the survey was used to collect information on the occurrence of zoonotic diseases, gastrointestinal illnesses, respiratory problems, dermatoses, and women's reproductive health issues. Of the 624 respondents, 10.4% (n = 65) reported that they had contracted a disease from an animal. Interestingly, only 9 respondents indicated that they had suffered from foodborne illnesses in the past year including salmonellosis (n = 1), campylobacteriosis (n = 1), and gastroenteritis due to Escherichia coli (n = 1). A risk factor associated with difficulty breathing was the lack of use of a breathing mask, whereas ventilation in the free stall area appeared to offer a protective effect. Difficulty breathing was reported by 9.8% (n = 61) of the respondents. Risk factors associated with skin disorders included raising fruits and/or vegetables, raising swine, and not wearing gloves when milking. The findings of the study suggest that many of the illnesses and conditions could have been acquired by working with dairy animals and their environment. Based on the findings of this study, additional investigations on the causes and prevention of these illnesses are warranted.

Occupational health behaviors and habits of women on dairy farms in Pennsylvania.

The goal of this study was to determine what tasks women perform, behaviors that could result in exposure to zoonotic disease, and preventative measures practiced by women on dairy farms. A written survey was sent to a stratified, random sample of dairy farms in Pennsylvania (n = 3709) using a modified version of the Dillman method. The tasks most commonly performed by the respondents (n = 624) included milking (70.8%), feeding (60.6%), and cleaning stalls (42.6%). The use of personal protective equipment was infrequent. Gloves were always worn when milking by 32.7%. More respondents, 96.5%, changed their clothes at least sometimes before working in the barn as compared to when leaving the barn. Handwashing was always performed by 86.7% after assisting with delivering calves, whereas 71.1% always washed their hands after milking. Eating and drinking in the barn were practiced by 45.0% and 72.0%, respectively. Veterinary obstetric drugs were administered by 28.2% of the respondents. Most of the respondents, 89.7%, indicated that they felt they had minimal to no risk of contracting a disease from the animals with which they worked.

Reason for visit: is migrant health care that different?

PURPOSE: The purpose of this pilot study was to determine the reasons for which migrant agricultural workers in Pennsylvania seek health care. METHODS: Participants were individuals 14 years of age and over, actively involved in agricultural labor and presenting for medical care at 6 migrant health care centers. Bilingual health care providers randomly selected and interviewed the participants. FINDINGS: The most commonly reported reason for visiting the health care provider was for physical examination. The most frequent acute problems were related to the musculoskeletal and integumentary systems. Frequently cited problems in the medical history were hypertension, musculoskeletal/back pain, and gastrointestinal conditions. Most medications being taken were for cardiovascular or pain-related problems. CONCLUSIONS: These results suggest that migrant workers present with medical problems that are similar to those of the general primary care population. Many problems were recurrent and represented common chronic medical conditions.

Short-term and long-term reproducibility of lung tumor position using active breathing control (ABC).

PURPOSE: To evaluate the short-term and long-term reproducibility of lung tumor position for scans acquired using an active breathing control (ABC) device. METHODS AND MATERIALS: Ten patients with lung cancer were scanned over three sessions during the course of treatment. For each session, two scans were acquired at deep inhale, and one scan each at half of deep inhale and at exhale. Long-term reproducibility was evaluated by comparing the same breathing state scans from two sessions, with setup variation removed by skeletal alignment. Tumor alignment was based on intensity matching of a small volume around the tumor. For short-term reproducibility, the two inhale volumes from the same session were compared. RESULTS: For the short-term reproducibility, the mean and the standard deviation (SD) of the displacement of the center of tumor were 0.0 (1.5) mm in anteroposterior (AP), 0.3 (1.4) mm in superior/inferior (SI), and 0.2 (0.7) mm in right/left (RL) directions. For long-term reproducibility, the mean (SD) were -1.3 (3.1) mm AP, -0.5 (3.8) mm SI, and 0.3 (1.6) mm RL for inhale and -0.2 (2.8) mm AP, 0.2 (2.1) mm SI, and -0.7 (1.1) mm RL for exhale. CONCLUSION: The ABC device demonstrates very good short-term and long-term reproducibility. Increased long-term variability in position, primarily in the SI and AP directions, indicates the role of tumor-directed localization in combination with breath-held immobilization.

Survey of health needs and concerns of rural Pennsylvanians.

INTRODUCTION: This survey was undertaken to determine the most important health and safety needs of farmers and rural citizens of Pennsylvania. METHODS: In June of 2004, a one-page questionnaire was distributed by mail to 32,700 members of the Pennsylvania Farm Bureau as an attachment to their monthly newsletter. RESULTS: The lack of affordable health care insurance was overwhelmingly cited as the most important unmet health care need (73%). No other issue was chosen by more than 10 percent of respondents. This lack of affordable health insurance was also cited as the most important health or safety problem to be addressed in the respondent's communities (71%). When asked the most important health or safety problem affecting them as individuals or their community, the respondents chose "no major problem or need" as the most frequent response (46%). The issue of affordable health insurance was not an option for this question. The predominant concern regarding the lack of affordable health insurance was consistent across all regions of the Commonwealth and for farmers as well as residents of all community sizes sampled. DISCUSSION: This study would indicate that the lack of affordable health insurance is the preeminent health and safety issue for many Pennsylvania farmers and rural citizens.

Results following treatment to doses of 92.4 or 102.9 Gy on a phase I dose escalation study for non-small cell lung cancer.

BACKGROUND AND PURPOSE: The University of Michigan lung dose escalation study has increased the dose of external beam radiation for non-small cell lung cancer based on the volume of normal lung irradiated. The results of patients treated to either 92.4 or 102.9 Gy are reported. MATERIALS AND METHODS: Seventeen patients have completed treatment to 92.4 or 102.9 Gy and have been followed for at least 6 months. The treatment planning goal was to minimize the effective volume (V(eff)) of total lung irradiated as computed using the Kutcher-Burman DVH reduction scheme. Dose was escalated independently within each of five V(eff) bins. Toxicity, freedom from local progression (FFLP), overall survival (OS) and cause specific survival (CSS) are reported. RESULTS: Thirteen patients were Stage I, one was Stage II and three were Stage III. V(eff) ranged from 0.06 to 0.21. The median pretreatment FEV(1) was 1.24 L or 44% of predicted. Median follow-up for survivors was 37.9 months. No patient had significant pulmonary toxicity. One patient each had grades 2 and 3 esophagitis. Median percent change in FEV1 was -11%. Two- and three-year actuarial FFLP and OS rates for the entire group were 68 and 58% and 51 and 26%, respectively. For Stage I patients, the 2 and 3 year FFLP, OS and CSS rates were 82 and 68%, 54 and 33%, 76 and 48% respectively. CONCLUSIONS: These results suggest that doses of radiation of 92.4 and 102.9 Gy can be delivered safely to limited lung volumes with minimal toxicity.

Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability.

PURPOSE: To compare different normal tissue complication probability (NTCP) models to predict the incidence of radiation pneumonitis on the basis of the dose distribution in the lung. METHODS AND MATERIALS: The data from 382 breast cancer, malignant lymphoma, and inoperable non-small-cell lung cancer patients from two centers were studied. Radiation pneumonitis was scored using the Southwestern Oncology Group criteria. Dose-volume histograms of the lungs were calculated from the dose distributions that were corrected for dose per fraction effects. The dose-volume histogram of each patient was reduced to a single parameter using different local dose-effect relationships. Examples of single parameters were the mean lung dose (MLD) and the volume of lung receiving more than a threshold dose (V(Dth)). The parameters for the different NTCP models were fit to patient data using a maximum likelihood analysis. RESULTS: The best fit resulted in a linear local dose-effect relationship, with the MLD as the resulting single parameter. The relationship between the MLD and NTCP could be described with a median toxic dose (TD(50)) of 30.8 Gy and a steepness parameter m of 0.37. The best fit for the relationship between the V(Dth) and the NTCP was obtained with a D(th) of 13 Gy. The MLD model was found to be significantly better than the V(Dth) model (p <0.03). However, for 85% of the studied patients, the difference in NTCP calculated with both models was <10%, because of the high correlation between the two parameters. For dose distributions outside the range of the studied dose-volume histograms, the difference in NTCP, using the two models could be >35%. For arbitrary dose distributions, an estimate of the uncertainty in the NTCP could be determined using the probability distribution of the parameter values of the Lyman-Kutcher-Burman model. CONCLUSION: The maximum likelihood method revealed that the underlying local dose-effect relation for radiation pneumonitis was linear (the MLD model), rather than a step function (the V(Dth) model). Thus, for the studied patient population, the MLD was the most accurate predictor for the incidence of radiation pneumonitis.

Adjuvant external beam radiation therapy with concurrent chemotherapy in the management of gallbladder carcinoma.

PURPOSE: This study was performed to evaluate the outcome of patients with gallbladder cancer who received postoperative concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Curative resection followed by adjuvant combined modality therapy with external beam radiation therapy (EBRT) and chemotherapy was attempted in 21 consecutive gallbladder carcinoma (GBC) patients at the Mayo Clinic from 1985 through 1997. All patients received concurrent 5-fluorouracil during EBRT. EBRT fields encompassed the tumor bed and regional lymph nodes (median dose of 54 Gy in 1.8-2.0-Gy fractions). One patient received 15 Gy intraoperatively after EBRT. A retrospective analysis was performed for the end points of local control, distant failure, and overall survival. RESULTS: After maximal resection, 12 patients had no residual disease on pathologic evaluation, 5 had microscopic residual disease, and 4 had gross residual disease. One patient had Stage I disease, and 20 had Stage III-IV disease. With median follow-up of 5 years (range: 2.6-11.5 years), 5-year survival for the entire cohort was 33%. The 5-year survival rate of patients with Stage I-III disease was 65% vs. 0% for those with Stage IV disease (p < 0.02). For patients with no residual disease, 5-year survival was 64% vs. 0% for those with residual disease (p = 0.002). The median survival was 0.6, 1.4, and 5.1 years for patients with gross residual, microscopic residual, and no residual disease, respectively (p = 0.02). The 5-year local control rate for the entire cohort was 73%. Two-year local control rates were 0%, 80%, and 88% for patients with gross residual, microscopic residual, or no residual disease, respectively (p < 0.01). Five-year local control rates were 100% for the 6 patients who received total EBRT doses >54 Gy (microscopic residual, 3 patients; gross residual, 1 patient; negative but narrow margins, 2 patients) vs. 65% for the 15 who received a lower dose (3, gross residual; 2, microresidual; 10, negative margins). CONCLUSION: Patients with completely resected (negative margins) GBC followed by adjuvant EBRT plus 5-fluorouracil chemotherapy had a relatively favorable prognosis, with a 5-year survival rate of 64%. These results seem to be superior to historical surgical controls from the Mayo Clinic and other institutions, which report 5-year survival rates of approximately 33% with complete resection alone. Both tumor stage and extent of resection seemed to influence survival and local control. More aggressive measures using current cancer therapies and integration of new cancer treatment modalities will be required to favorably impact on the poor prognosis of patients with Stage IV or subtotally resected GBC. Additional investigation leading to earlier diagnosis is warranted, because most patients with GBC present with advanced disease.

Policy and organizational issues in agromedicine: a survey of 2001 NAAC meeting attendees.

The field of agromedicine faces numerous policy and organizational development challenges as it enters the 21st Century. To gauge these, the authors surveyed attendees of the 14th Annual Meeting of the North American Agromedicine Consortium (NAAC) in Charleston, South Carolina, in November 2001. Survey questions dealt with agromedicine policy issues, organizational/programmatic issues, the agromedicine core areas, the usefulness of state reports at the meeting, and important policy, organizational and programmatic issues that were missing from, or insufficiently covered at the meeting. While respondents clearly saw serious obstacles facing agromedicine as it continues to develop, they also felt that the NAAC and the profession served important roles in furthering education, research and client service.