Review of current best practice and priorities for research in radiation oncology for elderly patients with cancer: the International Society of Geriatric Oncology (SIOG) task force.

Radiotherapy (RT) is a key component of the management of older cancer patients. Level I evidence in older patients is limited. The International Society of Geriatric Oncology (SIOG) established a task force to make recommendations for curative RT in older patients and to identify future research priorities. Evidence-based guidelines are provided for breast, lung, endometrial, prostate, rectal, pancreatic, oesophageal, head and neck, central nervous system malignancies and lymphomas. Patient selection should include comorbidity and geriatric evaluation. Advances in radiation planning and delivery improve target coverage, reduce toxicity and widen eligibility for treatment. Shorter courses of hypofractionated whole breast RT are safe and effective. Conformal RT and involved-field techniques without elective nodal irradiation have improved outcomes in non-small-cell lung cancer (NSCLC) without increasing toxicity. Where comorbidities preclude surgery, stereotactic body radiotherapy (SBRT) is an option for early-stage NSCLC and pancreatic cancer. Modern involved-field RT for lymphoma based on pre-treatment positron emission tomography data has reduced toxicity. Significant comorbidity is a relative contraindication to aggressive treatment in low-risk prostate cancer (PC). For intermediate-risk disease, 4-6 months of hormones are combined with external beam radiotherapy (EBRT). For high-risk PC, combined modality therapy (CMT) is advised. For high-intermediate risk, endometrial cancer vaginal brachytherapy is recommended. Short-course EBRT is an alternative to CMT in older patients with rectal cancer without significant comorbidities. Endorectal RT may be an option for early disease. For primary brain tumours, shorter courses of postoperative RT following maximal debulking provide equivalent survival to longer schedules. MGMT methylation status may help select older patients for temozolomide alone. Stereotactic RT provides an alternative to whole-brain RT in patients with limited brain metastases. Intensity-modulated radiation therapy provides an excellent technique to reduce dose to the carotids in head and neck cancer and improves locoregional control in oesophageal cancer. Best practice and research priorities are summarised.

Preliminary results of Radiation Therapy Oncology Group 97-03: a randomized phase ii trial of concurrent radiation and chemotherapy for advanced squamous cell carcinomas of the head and neck.

PURPOSE: To define further the role of concurrent chemoradiotherapy for patients with advanced squamous carcinoma of the head and neck. PATIENTS AND METHODS: The Radiation Therapy Oncology Group developed this three-arm randomized phase II trial. Patients with stage III or IV squamous carcinoma of the oral cavity, oropharynx, or hypopharynx were eligible. Each of three arms proposed a radiation schedule of 70 Gy in 35 fractions. Patients on arm 1 were to receive cisplatin 10 mg/m(2) daily and fluorouracil (FU) 400 mg/m(2) continuous infusion (CI) daily for the final 10 days of treatment. Treatment on arm 2 consisted of hydroxyurea 1 g every 12 hours and FU 800 mg/m(2)/d CI delivered with each fraction of radiation. Arm 3 patients were to receive weekly paclitaxel 30 mg/m(2) and cisplatin 20 mg/m(2). Patients randomly assigned to arms 1 and 3 were to receive their treatments every week; patients on arm 2 were to receive their therapy every other week. RESULTS: Between 1997 and 1999, 241 patients were entered onto study; 231 were analyzable. Ninety-two percent, 79%, and 83% of patients on arms 1, 2, and 3, respectively, were able to complete their radiation as planned or with an acceptable variation. Fewer than 10% of patients had unacceptable deviations or incomplete chemotherapy in the three arms. Estimated 2-year disease-free and overall survival rates were 38.2% and 57.4% for arm 1, 48.6% and 69.4% for arm 2, and 51.3% and 66.6% for arm 3. CONCLUSION: We have demonstrated that three different approaches of concurrent multiagent chemotherapy and radiation were feasible and could be delivered to patients in a multi-institutional setting with high compliance rates.

Comparison of high dose-rate and low dose-rate dose distributions for vaginal cylinders.

PURPOSE: The identification of appropriate high dose-rate parameters required to produce a "uniform" dose distribution on the surface of a vaginal cylinder. The high dose-rate dose distribution is then compared to the traditional low dose-rate dose distributions obtained with Burnett cylinders. METHODS AND MATERIALS: Dose distributions were calculated for 2, 3, and 3.5 cm diameter Burnett cylinders with and without crossing sources. Three models for the high dose-rate cylinders were developed and compared. High dose-rate dose distributions were calculated for 2, 3, and 3.5 cm diameter cylinders with and without anisotropic corrections for various dose specification points. RESULTS: Low dose-rate distributions are not uniform over the surface of the applicator. The exact distribution depends upon cylinder diameter and upon the exact source loading. High dose rate dose distributions can be configured to provide for a "uniform" dose on the surface, if an apex dose specification point is used together with dose specification points on the surface of the applicator opposite each dwell position. CONCLUSIONS: The conversion of low dose rate techniques to high dose rate techniques for vaginal cylinders involves an appreciation of the details of dose distributions of both approaches. The comparison between traditional low dose-rate distributions and high dose-rate distributions shows that, unlike the low dose-rate distributions, a relatively uniform high dose-rate distribution can be obtained independent of cylinder diameter. The clinical significance of the differences in the low dose-rate and high dose-rate dose distributions remains to be determined by long-term follow up of patients treated with high dose-rate techniques.

Pulmonary function changes in long-term survivors of bone marrow transplantation.

PURPOSE: This study was undertaken to evaluate long-term pulmonary function changes in patients undergoing bone marrow transplantation (BMT), to assess their clinical significance, and to identify factors influencing these changes. METHODS AND MATERIALS: Pulmonary function tests (PFT) were evaluated before and after BMT in 111 adult patients undergoing BMT between 1985 and 1991. Forced expiratory volume at 1 s (FEV1), forced vital capacity (FVC), diffusing capacity (DLCO), and total lung capacity (TLC) were evaluated. One hundred and three patients (92.8%) received total body irradiation (TBI) to a total dose of 14 Gy in nine equal fractions. The lung dose was restricted to < 6.5 Gy in 95% of patients with partial transmission lung shielding. Seventy-eight percent of patients had acute graft-versus-host disease (aGVHD), 69% chronic graft-vs.-host disease (cGVHD), and 63% posttransplant pulmonary infection. Effects of GVHD, TBI, radiation dose to the lungs, dose rate of TBI, posttransplant pulmonary infection, Busulfan use for conditioning, age, and history of smoking were evaluated for their influence on pulmonary function. RESULTS: Posttransplant FEV1, FVC, and TLC were lower than pretransplant values (p < 0.05) at 6 months and 1 year posttransplant with subsequent recovery. DLCO was significantly lower at all posttransplant intervals. FEV1 did not fall significantly in patients without acute or chronic GVHD and recovered earlier than in patients without posttransplant pulmonary infection. Recovery of FVC, TLC, and DLCO was also delayed in patients with acute and chronic GVHD and posttransplant pulmonary infection. Multiple regression analysis revealed an association between a higher radiation dose to the lungs, and decreased FVC at 2 years (p = 0.01). Progressive obstructive pulmonary disease was not observed. CONCLUSION: An initial decline in PFTs with subsequent recovery was observed. Factors associated with delayed recovery and incomplete recovery of PFTs were GVHD, posttransplant pulmonary infection, and higher radiation dose to the lungs. The conditioning regimen used at Medical College of Wisconsin, including relatively high TBI doses with partial transmission pulmonary shielding, appears to be well tolerated by the lungs in long-term survivors. No progressive decline in PFTs or symptomatic decline in pulmonary function was observed during the time interval studied.

Outcome and predictors of outcome in pediatric submersion victims receiving prehospital care in King County, Washington.

Predictors of outcome in pediatric submersion victims treated by Seattle and King County's prehospital emergency services were studied. Victims less than 20 years old were identified from hospital admissions and paramedic and medical examiners' reports. The proportion of fatal or severe outcomes in patients were compared with various risk factors. Of 135 patients, 45 died and 5 had severe neurologic impairment. A subset of 38 victims found in cardiopulmonary arrest had a 32% survival rate, with 67% of survivors unimpaired or only mildly impaired. The two risk factors that occurred most commonly in victims who died or were severely impaired were submersion duration greater than 9 minutes (28 patients) and cardiopulmonary resuscitation duration longer than 25 minutes (20 patients). Both factors were ascertained in the prehospital phase of care. Submersion duration was associated with a steadily increasing risk of severe or fatal outcomes: 10% risk (7/67) for 0 to 5 minutes, 56% risk (5/9) for 6 to 9 minutes, 88% risk (21/25) for 10 to 25 minutes, 100% risk (4/4) for greater than 25 minutes. None of 20 children receiving greater than 25 minutes of cardiopulmonary resuscitation escaped death or severe neurologic impairment. Our rates for saving all victims, particularly victims in cardiopulmonary arrest, are considerably higher than has been reported before the children. Prompt prehospital advanced cardiac life support is the most effective means of medical intervention for the pediatric submersion victim. Prehospital information provided the most valuable predictors of outcome.

Ten-year study of pediatric drownings and near-drownings in King County, Washington: lessons in injury prevention.

The factors associated with submersion events among less than 20-year-old persons that occurred in King County from 1974 to 1983 were studied to focus prevention efforts. Near-drowning (n = 103) and drowning (n = 96) victims were identified from medical examiners' reports, paramedics' reports, and hospital discharge registers. Annual incidence was 5.5; the mortality rate was 2.6 per 100,000 children. Although preschool-aged children had the largest incidence (12.8), followed by older adolescents (4.9), adolescents had the largest case fatality rate, 77%. Lake and river victims had the largest incidence, mortality, and case fatality rate; swimming pools, the smallest case fatality rate (25%). A total of 89% of all victims had absent or no supervision; victims supervised by lifeguards had a 42% case fatality rate. Prior seizures were part of the history of 7.5% of all victims; 25% of fatal submersions by adolescents were associated with alcohol. Bathtub submersions were associated with child abuse in three of 16 preschool-aged children and epilepsy in four of five older children. Certain age groups and sites combined had the greatest incidence: preschool-aged children in swimming pools, infants in bathtubs, teenagers in lakes and rivers. Incidence decreased in public and semipublic pools coincident with fencing regulations. These findings suggest prevention strategies: extending fencing requirements to private pools, discouraging alcohol consumption during water sports, changing bathing practices of epileptics, and improving lifeguard efficacy.

A controlled time-series trial of clinical reminders: using computerized firm systems to make quality improvement research a routine part of mainstream practice.

OBJECTIVE: To explore the feasibility of conducting unobtrusive interventional research in community practice settings by integrating firm-system techniques with time-series analysis of relational-repository data. STUDY SETTING: A satellite teaching clinic divided into two similar, but geographically separated, primary care group practices called firms. One firm was selected by chance to receive the study intervention. Forty-two providers and 2,655 patients participated. STUDY DESIGN: A nonrandomized controlled trial of computer-generated preventive reminders. Net effects were determined by quantitatively combining population-level data from parallel experimental and control interrupted time series extending over two-month baseline and intervention periods. DATA COLLECTION: Mean rates at which mammography, colorectal cancer screening, and cholesterol testing were performed on patients due to receive each maneuver at clinic visits were the trial's outcome measures. PRINCIPAL FINDINGS: Mammography performance increased on the experimental firm by 154 percent (0.24 versus 0.61, p = .03). No effect on fecal occult blood testing was observed. Cholesterol ordering decreased on both the experimental (0.18 versus 0.1 1, p = .02) and control firms (0.13 versus 0.07, p = .03) coincident with national guidelines retreating from recommending screening for young adults. A traditional uncontrolled interrupted time-series design would have incorrectly attributed the experimental-firm decrease to the introduction of reminders. The combined analysis properly indicated that no net prompting effect had occurred, as the difference between firms in cholesterol testing remained stochastically stable over time (0.05 versus 0.04, p = .75). A logistic-regression analysis applied to individual-level data produced equivalent findings. The trial incurred no supplementary data collection costs. CONCLUSIONS: The apparent validity and practicability of our reminder implementation study should encourage others to develop computerized firm systems capable of conducting controlled time-series trials.

Safety of aerosol tobramycin administration for 3 months to patients with cystic fibrosis.

To determine the potential toxicity of prolonged aerosol tobramycin administration, 22 patients with cystic fibrosis were monitored while receiving inhaled tobramycin three times a day for 12 weeks. Prior to, four times during administration and approximately 6 weeks after discontinuation of treatment, we assessed pulmonary function, weight, height, body temperature, eighth cranial nerve function, serum creatinine, blood urea nitrogen, urinary creatinine clearance, plasma iothalamate clearance, urinary beta-2 microglobulin concentration, and Pseudomonas aeruginosa density in sputum. There was no detectable laboratory evidence of nephrotoxicity. Neither a decrease in auditory acuity (range 250-20,000 Hz) nor vestibular dysfunction was detected. Pulmonary function tests significantly improved during the first month in all subjects (P less than 0.05) but returned to enrollment values by the end of the 12th week of administration of tobramycin aerosol. Sputum P. aeruginosa density initially decreased from a mean of 10(7) cfu/gm to a mean of 10(4) cfu/gm after 2 weeks of aerosol tobramycin administration and remained significantly below the enrollment value throughout. Coincident with the reduced bacterial density, a reduction in cough frequency and sputum production, as well as a weight gain was observed. Seventy-three percent of the patients with sputum P. aeruginosa isolates susceptible to tobramycin on enrollment yielded resistant organisms during aerosol administration. However, 1 year later all sputum P. aeruginosa isolates obtained from patients were susceptible to tobramycin. We conclude that thrice daily aerosol tobramycin administration for 3 months is not associated with detectable eighth cranial nerve or renal toxicity. Transient emergence of tobramycin resistant P. aeruginosa may occur.

Two decades of experience in the University of Washington Family Medicine Residency Network: practice differences between graduates in rural and urban locations.

This study describes how graduates of the University of Washington Family Medicine Residency Network who practice in rural locations differ from their urban counterparts in demographic characteristics, practice organization, practice content and scope of services, and satisfaction. Five hundred and three civilian medical graduates who completed their residencies between 1973 and 1990 responded to a 27-item questionnaire sent in 1992 (84% response rate). Graduates practicing outside the United States in a specialty other than family medicine or for fewer than 20 hours per week in direct patient care were excluded from the main study, leaving 116 rural and 278 urban graduates in the study. Thirty percent of graduates reported practicing in rural counties at the time of the survey. Rural graduates were more likely to be in private and solo practices than urban graduates. Rural graduates spent more time in patient care and on call, performed a broader range of procedures, and were more likely to practice obstetrics than urban graduates. Fewer graduates in rural practice were women. A greater proportion of rural graduates had been defendants in medical malpractice suits. The more independent and isolated private and solo practice settings of rural graduates require more practice management skills and support. Rural graduates' broader scope of practice requires training in a full range of procedures and inpatient care, as well as ambulatory care. Rural communities and hospitals also need to develop more flexible practice opportunities, including salaried and part-time positions, to facilitate recruitment and retention of physicians, especially women.

An evaluation of computerized documentation of resident experiences in training.

This paper describes an evaluation of the University of Washington family practice project to document resident experiences in training. The production of aggregate reports using clustering techniques and peer group comparisons were well received by residents and faculty. A questionnaire survey and personal interview with a sample of faculty and residents analyzed attitudes toward the usefulness of such a documentation system as well as the actual uses of the reports produced. Documentation of inpatient and outpatient procedures was the most highly regarded application, but an overview of the scope and content of a resident ambulatory practice experience was also considered useful. Physician behavior was altered in subtle ways as a result of the feedback.

Preclinical development of keliximab, a Primatized anti-CD4 monoclonal antibody, in human CD4 transgenic mice: characterization of the model and safety studies.

The preclinical safety assessment of biopharmaceuticals necessitates that studies be conducted in species in which the products are pharmacologically active. Monoclonal antibodies are a promising class of biopharmaceuticals for many disease indications; however, by design, these agents tend to have limited species cross-reactivity and tend to only be active in primates. Keliximab is a human-cynomolgus monkey chimeric (Primatized) monoclonal antibody with specificity for human and chimpanzee CD4. In order to conduct a comprehensive preclinical safety assessment of this antibody to support chronic treatment of rheumatoid arthritis in patients, a human CD4 transgenic mouse was used for chronic and reproductive toxicity studies and for genotoxic studies. In addition, immunotoxicity studies were conducted in these mice with Candida albicans, Pneumocystis carinii and B16 melanoma cells to assess the effects of keliximab on host resistance to infection and immunosurveillance to neoplasia. The results of these studies found keliximab to be well tolerated with the only effects observed being related to its pharmacologic activity on CD4+ T lymphocytes. The use of transgenic mice expressing human proteins provides a useful alternative to studies in chimpanzees with biopharmaceutical agents having limited species cross-reactivity.

Hospital privileges for family physicians: documentation of family practice residents' experiences in training.

This report describes a study of the content and uses of the University of Washington Affiliated Residency Network documentation system for future hospital privileges. The selected procedures and problems considered important to document for future hospital privileges were validated by means of a graduate survey conducted in 1985. Fifty percent of the 43 graduates responding used their personal documentation when applying for hospital privileges. Intermediate-sized hospitals of 50 to 199 beds were significantly more likely to require documentation than either small (fewer than 50 beds) or large (more than 200 beds) hospitals. However, 84 percent of the hospitals where graduates are located either require documentation or would find it helpful for privilege application. The three-year cumulative experiences of the 1986 cohort of graduating residents are also presented. Thirty-six of the residents (71 percent) participated actively in the voluntary network documentation system. None of the items selected as important to document for future hospital privileges were recorded by 100 percent of the residents. Obstetric procedures and problems were the items most commonly documented.

Content of the model teaching unit ambulatory care training and continuity of care in six family practice residency programs.

This article summarizes the practice content and continuity for 35 senior residents in six family medicine residency model teaching units utilizing a computerized information management system. Comparisons are drawn with the content of family practices in the National Ambulatory Medical Care Survey (NAMCS), showing that family medicine third-year residents provide a large proportion of pregnancy care and general medical examinations and treat a smaller number of chronic illness patients compared with family physicians in practice. Third-year residents performed few surgical procedures in the model teaching units. Continuity of care, though espoused by family medicine residencies in principle, was deficient in the model teaching units studied. Intensive training to compensate for these deficiencies is recommended.

Wadia type olivopontocerebellar degeneration: a case history and review of literature.

Olivocerebellar pontine degeneration of the Wadia type is characterized by progressive symmetrical cerebellar ataxia, slow eye movements, absent deep tendon reflexes, autosomal dominant inheritance, and onset between the second and fourth decades. The only available treatments are genetic counseling, social and psychological support, and physiotherapy. This article presents a case of this subtype of hereditary ataxia and a review of the literature.

Flying and midface fractures: the truth is out there.

There are no clear, evidence-based guidelines that dictate when it is safe for a patient to fly after sustaining a midface fracture. From January 2006 to December 2009, the Royal Darwin Hospital Maxillofacial Unit had 48 out of 201 patients with an orbital fracture that involved a paranasal air sinus transported by a variety of aircraft to the unit for definitive management. No orbital complications were recorded for the 24% of patients requiring air travel to our tertiary referral centre. Furthermore, there were no recorded deviations from the standard flight plan. We believe that this demonstrates there are no absolute contraindications to flying on a variety of aircraft with a midface fracture, but clinical assessment remains crucial for an informed decision to transport these patients by air.

RTOG 0518: randomized phase III trial to evaluate zoledronic acid for prevention of osteoporosis and associated fractures in prostate cancer patients.

BACKGROUND: RTOG 0518 evaluated the potential benefit of zoledronic acid therapy in preventing bone fractures for patients with high grade and/or locally advanced, non-metastatic prostate adenocarcinoma receiving luteinizing hormone-releasing hormone (LHRH) agonist and radiotherapy (RT). METHODS: Eligible patients with T-scores of the hip (<-1.0, but >-2.5 vs >-1.0) and negative bone scans were prospectively randomized to either zoledronic acid, 4 mg, concurrently with the start of RT and then every six months for a total of 6 infusions (Arm 1) or observation (Arm 2). Vitamin D and calcium supplements were given to all patients. Secondary objectives included quality of life (QOL) and bone mineral density (BMD) changes over a period of three years. RESULTS: Of 109 patients accrued before early closure, 96 were eligible. Median follow-up was 36.3 months for Arm 1 and 34.8 months for Arm 2. Only two patients experienced a bone fracture (one in each arm) resulting in no difference in freedom from any bone fracture (P=0.95), nor in QOL. BMD percent changes from baseline to 36 months were statistically improved with the use of zoledronic acid compared to observation for the lumbar spine (6% vs -5%, P<0.0001), left total hip (1% vs -8%, P=0.0002), and left femoral neck (3% vs -8%, P=0.0007). CONCLUSIONS: For patients with advanced, non-metastatic prostate cancer receiving LHRH agonist and RT, the use of zoledronic acid was associated with statistically improved BMD percent changes. The small number of accrued patients resulted in decreased statistical power to detect any differences in the incidence of bone fractures or QOL.

Emergence of a limit cycle for swimming microorganisms in a vortical flow of a viscoelastic fluid.

We propose that the rheological properties of background fluid play an important role in the interaction of microorganisms with the flow field. The viscoelastic-induced migration of microorganisms in a vortical flow leads to the emergence of a limit cycle. The shape and formation rate of patterns depend on motility, vorticity strength, and rheological properties of the background fluid. Given the inherent viscoelasticity of exopolysaccharides secreted by microorganisms, our results can suggest new mechanisms leading to the vital behavior of microorganisms such as bacterial aggregation and biofilm formation.