Hormone therapy for postmenopausal osteoporosis management.

Menopausal hormone therapy (MHT) has been used for prevention and treatment of postmenopausal osteoporosis for several decades. However, public concerns were raised over the safety of MHT after the initial report was published in 2002 by the Women's Health Initiative. We conducted a historical review on this subject, primarily focusing on level I evidence from randomized controlled trials, systematic reviews and meta-analyses, and summarized high-quality evidence on the efficacy and safety of MHT in management of postmenopausal osteoporosis. Clinical issues were also discussed on MHT initiation, identification of treatment candidates and treatment duration, as well as discontinuation of MHT.

Uterine bleeding with hormone therapies in menopausal women: a systematic review.

Uterine bleeding is a common reason why women discontinue menopausal hormone therapy (HT). This systematic review compared bleeding profiles reported in studies for continuous-combined HT approved in North America and Europe for moderate to severe vasomotor symptoms in postmenopausal women with a uterus. Non-head-to-head studies showed that uterine bleeding varies by formulation and administration route, with oral having a better bleeding profile than transdermal formulations. Cumulative amenorrhea over a year ranged from 18 to 61% with oral HT and from 9 to 27% with transdermal HT, as reported for continuous-combined HT containing 17ß-estradiol (E2)/progesterone (P4) (56%), E2/norethisterone acetate (NETA) (49%), E2/drospirenone (45%), conjugated equine estrogens/medroxyprogesterone acetate (18-54%), ethinyl estradiol/NETA (31-61%), E2/levonorgestrel patch (16%), and E2/NETA patch (9-27%). Amenorrhea rates and the mean number of bleeding/spotting days improved over time. The oral E2/P4 combination was amongst those with lower bleeding rates and may be an appropriate alternative for millions of women seeking bioidentical HT and/or those who have bleeding concerns with other HT.

Treatment of moderate to severe dyspareunia with intravaginal prasterone therapy: a review.

The loss of sex steroids (e.g. estradiol, dehydroepiandrosterone [DHEA], progesterone) that causes menopause commonly affects a woman's general health and produces bothersome physical changes that may interfere with normal sexual and genitourinary functioning. Although both over-the-counter and prescription treatments are available, there remains a large unmet need, as less than 10% of women are treated. Adrenal DHEA and its sulfate are the most abundant steroids in humans. Here we review the development of intravaginal prasterone, the synthetic equivalent to endogenous DHEA. Prasterone is approved by the US Food and Drug Administration for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Prasterone has been shown to decrease the pain associated with dyspareunia, and to improve vaginal pH, as well as superficial and parabasal cell counts, while maintaining serum hormone levels within the range of those seen in normal postmenopausal women. Unlike other menopausal prescription therapies, intravaginal prasterone does not carry a boxed warning, thus allowing the clinician and patient to engage in meaningful and reassuring discussion around a new approach that treats this common, debilitating condition.

TX-004HR clinically improves symptoms of vulvar and vaginal atrophy in postmenopausal women.

Objective: This study aimed to evaluate improvement of dyspareunia and associated vaginal dryness with a 17ß-estradiol softgel vaginal insert (TX-004HR; TherapeuticsMD, Boca Raton, FL, USA) in women with postmenopausal vulvar and vaginal atrophy (VVA). Methods: Postmenopausal women with VVA and moderate to severe dyspareunia received TX-004HR (4, 10, or 25 µg) or placebo in the 12-week, randomized, double-blind, placebo-controlled, phase 3 REJOICE trial. Post hoc analyses examined improvement levels in dyspareunia and concurrent vaginal dryness with TX-004HR and assessed the effects of patient characteristics on vaginal dryness treatment. Results: Significantly more women treated with TX-004HR (all doses) than placebo had complete resolution or substantial improvement in dyspareunia or vaginal dryness (concurrent with dyspareunia) by 12 weeks, observed as early as week 2 with most doses. TX-004HR significantly improved both dyspareunia and vaginal dryness at least one level versus placebo by week 12 in women with both symptoms. Subgroup analyses showed TX-004HR improved vaginal dryness associated with dyspareunia regardless of age, body mass index, uterine status, prior pregnancy, and vaginal birth number. Conclusion: TX-004HR provided clinically meaningful improvements in dyspareunia and vaginal dryness associated with dyspareunia in postmenopausal women with VVA. Clinicians may be able to use this information when discussing patients' expectations regarding symptom improvement with the estradiol vaginal insert.

Estrogen therapy for osteoporosis in the modern era.

Menopause predisposes women to osteoporosis due to declining estrogen levels. This results in a decrease in bone mineral density (BMD) and an increase in fractures. Osteoporotic fractures lead to substantial morbidity and mortality, and are considered one of the largest public health priorities by the World Health Organization (WHO). It is therefore essential for menopausal women to receive appropriate guidance for the prevention and management of osteoporosis. The Women's Health Initiative (WHI) randomized controlled trial first proved hormonal therapy (HT) reduces the incidence of all osteoporosis-related fractures in postmenopausal women. However, the study concluded that the adverse effects outweighed the potential benefits on bone, leading to a significant decrease in HT use for menopausal symptoms. Additionally, HT was not used as first-line therapy for osteoporosis and fractures. Subsequent studies have challenged these initial conclusions and have shown significant efficacy of HT in various doses, durations, regimens, and routes of administration. These studies support that HT improves BMD and reduces fracture risk in women with and without osteoporosis. Furthermore, the studies suggest that low-dose and transdermal HT are less likely associated with the adverse effects of breast cancer, endometrial hyperplasia, coronary artery disease (CAD), and venous thromboembolism (VTE) previously observed in standard-dose oral HT regimens. Given the need for estrogen in menopausal women and evidence supporting the cost effectiveness, safety, and efficacy of HT, we propose that HT should be considered for the primary prevention and treatment of osteoporosis in appropriate candidates. HT should be individualized and the once "lowest dose for shortest period of time" concept should no longer be used. This review will focus on the prior and current studies for various HT formulations used for the prevention and treatment of osteoporosis, exploring the safety profile of low-dose and transdermal HT that have been shown to be safer than oral standard-dose HT.

Electrocution of Raptors on Power Lines: A Review of Necropsy Methods and Findings.

Decades after the problem was first identified, power line electrocution continues to be a cause of avian mortality. Currently, several federal laws protect eagles and other migratory birds, meaning that utility companies may be liable for electrocution-related deaths. Veterinarians and veterinary pathologists called upon to diagnose and treat electrocuted birds should keep this in mind when conducting clinical and postmortem examinations. This review details necropsy findings and methods used to diagnose electrocution. A combination of gross, subgross, and radiographic examinations can aid in identification of subtle injury. Diagnosis is made based on the presence of skin and/or feather burns. Other necropsy findings may include skin lacerations, subcutaneous burns, bruising, limb avulsion, hemopericardium, and vascular rupture. At the US Fish and Wildlife Service's National Forensics Laboratory, from 2000 to 2015, 417 raptor deaths were determined to have been caused by electrocution. Bald eagles and golden eagles were the most commonly submitted species. In a retrospective review of 377 cases, for which whole bodies were submitted, 18% of the electrocuted birds had only a single, small (less than 3 cm in diameter) external burn. Small, isolated burns tended to occur on the undersides of the wings at and distal to the elbow and on the lower legs and feet. These areas should be most carefully examined in cases where electrocution injury is not immediately apparent.

Treatment rates and healthcare costs of patients with fragility fracture by site of care: a real-world data analysis.

In a characterization of treatment rates and healthcare costs among patients with an osteoporotic-related fragility fracture overall and by site of care, costs were high and treatment rates were low. PURPOSE: Osteoporotic fractures can be debilitating, even fatal, among older adults. The cost of osteoporosis and related fractures is projected to increase to more than $25 billion by 2025. The objective of this analysis is to characterize disease-related treatment rates and healthcare costs of patients with an osteoporotic fragility fracture overall and by site of fracture diagnosis. METHODS: In this retrospective analysis, individuals with fragility fractures were identified in the Merative MarketScan® Commercial and Medicare Databases among women 50 years of age or older and diagnosed with fragility fracture between 1/1/2013 and 6/30/2018 (earliest fracture diagnosis = index). Cohorts were categorized by clinical site of care where the diagnosis of fragility fracture was made and were continuously followed for 12 months prior to and following index. Sites of care were inpatient admission, outpatient office, outpatient hospital, emergency room hospital, and urgent care. RESULTS: Of the 108,965 eligible patients with fragility fracture (mean age 68.8), most were diagnosed during an inpatient admission or outpatient office visit (42.7%, 31.9%). The mean annual healthcare costs among patients with fragility fracture were $44,311 (± $67,427) and were highest for those diagnosed in an inpatient setting ($71,561 ± $84,072). Compared with other sites of care at fracture diagnosis, patients diagnosed during an inpatient admission also had highest proportion of subsequent fractures (33.2%), osteoporosis diagnosis (27.7%), and osteoporosis therapy (17.2%) during follow-up. CONCLUSION: The site of care for diagnosis of fragility fracture affects treatment rates and healthcare costs. Further studies are needed to determine how attitude or knowledge about osteoporosis treatment or healthcare experiences differ at various clinical sites of care in the medical management of osteoporosis.

Osteoporosis management in post-menopausal women.

Osteoporosis is most prevalent in women over the age of 50 as the hormonal influence of estrogen on bone health dissipates with the onset of menopause. The progressive changes in bone structure, quality and density lead to pathological fractures and an increase in morbidity and mortality among menopausal women. This review will examine the 2010 North American Menopause Society (NAMS) position statement and other recent publications to summarize the data and combinations of therapies used to treat women 50 years or older with osteoporosis. To review the latest research and guidelines for osteoporosis management we performed a PubMed search using the parameters Linked to free full text, Humans, Female, Review, English, Middle Age (45-64 years and 45+ years), Age 65+ years, and published in the last five years. Articles were sorted by relevance and hand searching of these articles was done to further increase the yield. While a perfect treatment has yet to be discovered to completely cure this progressive disease, many breakthroughs have been made in order to prevent fractures and improve quality of life. Calcium and vitamin D supplementation are recommended for patients undergoing pharmacological treatment, however, trials looking at their effectiveness have mixed findings. Bisphosphonates are considered the first line therapy in the treatment of osteoporosis and reduce vertebral fractures by 40% to 70% and non-vertebral fractures by 20% to 35%. Calcitonin showed promise during early trials in 2000 with a 33% reduction in fractures but these results have not been replicated and this therapy is now relegated to a second line treatment. Teriparatide is recommended for patients with severe osteoporosis and has been shown to reduce vertebral fractures 65% and non-vertebral fractures 53%. Selective estrogen receptor modulators (SERMs) are another useful therapy resulting in a 55% reduction in vertebral fractures without any documented advantage when looking at non-vertebral fractures. The currently available SERMs for this indication include raloxifene, available in the USA, and bazedoxifene, in Europe. Estrogen is effective, with a 27% reduction in fractures, but often is reserved for concomitant use for other menopausal symptoms or in patients intolerant of other available osteoporosis therapies. The newly approved monoclonal antibody for osteoporosis treatment in postmenopausal women, denosumab, leads to a 68% and 19% reduction of vertebral and non-vertebral fractures, respectively. In conclusion, the 2010 NAMS position statement provides an excellent framework to discuss treatment options with patients. Lifestyle optimization should be the bedrock of any good treatment approach. When pharmacological intervention is warranted, many good therapies are available which have been shown to reduce the risk of fractures in osteoporotic patients. Any treatment plan, however, will be ineffective if the patient is not compliant. Therefore, a detailed discussion regarding each therapeutic intervention should ensue, including its usefulness and side effects.

Neuronal embryonal tumors in fish.

This article describes 11 cases of neuronal embryonal neoplasia in captive adult teleost fish. Neoplasms were located within 1 or both eyes of 8 fish and the skin of 3 other fish. Ocular neoplasms most often presented as unilateral or bilateral exophthalmia. Seven ocular and 1 cutaneous mass were composed of small triangular (carrot-shaped) neoplastic cells with Flexner-Wintersteiner-type rosette formation. Mass location and histologic and ultrastructural features were suggestive of retinoblastomas. One ocular mass was composed of ribbons and rosettes of neoplastic cells with multiple areas of neuronal differentiation and was diagnosed as a teratoid medulloepithelioma. A cutaneous mass from an electric eel (Electrophorus electricus) consisted of rosettes and streams of elongate neoplastic cells. The epidermal electroreceptor (ampullary) organ was considered as an origin. Although distant metastases were not observed, neoplasms were generally locally aggressive with postexcision recurrence. There was occasional spread to or de novo occurrence within the contralateral eye.

Morphologic evidence suggestive of hypertension in western gray kangaroos (Macropus fuliginosus).

Marked renal vascular changes, suggestive of hypertension, were present in adult western gray kangaroos (Macropus fuliginosus) from a single facility over a 14-year period. A subset of these kangaroos also had vague clinical nervous system deficits, including blindness. To characterize the vascular lesions, determine prevalence, and document other changes, case histories and archival tissue sections from 21 adult kangaroos (8 male, 13 female) that died or were euthanatized between 1994 and 2008 were reviewed. Relevant lesions included increased thickness of the renal arteriolar tunica media with smooth muscle hypertrophy and/or hyperplasia, accumulation of extracellular matrix within arterioles, increased vascular tortuosity, and varying degrees of juxtaglomerular hyperplasia. Renal tissue from two more severely affected animals was further examined by transmission electron microscopy, highlighting arteriolar endothelial cell hypertrophy and disruption of the medial architecture. Hypertrophy of arteries and arterioles in other organ systems was also present (3/21), including vessels in the brain and spinal cord of one animal with clinical neurologic signs. Four kangaroos had antemortem retinal detachment, a potential sequel of hypertension in humans and domestic mammals. The cause of these vascular lesions in this mob is uncertain. Lesions were not associated with an infectious disease process, age, underlying renal disease, or thyroid abnormalities. In the absence of other causes, hypertension was a differential. Further investigation into clinical significance and predisposing factors, such as genetics and diet, is warranted.

Molecular basis of antagonism between K70E and K65R tenofovir-associated mutations in HIV-1 reverse transcriptase.

The K70E mutation in HIV-1 reverse transcriptase was observed in 10% of virologic non-responders of the abacavir/lamivudine/tenofovir arm of ESS30009, alone, or in mixtures with K65R by population sequencing. Clonal analysis of six ESS30009 K70E isolates failed to identify double mutants carrying K65R+K70E. Site-directed K70E mutants had a replication capacity of 97+/-29%, but only 2.4+/-0.9% for K65R+K70E and 0.01% for K65R+K70E+M184V mutants. K65R+K70E phenotypic fold changes for abacavir, lamivudine and tenofovir were comparable to reported values for K65R alone. In molecular dynamic simulations, the epsilon-amino group of K65 was positioned 2.7+/-0.1A from the gamma-phosphate of the dTTP ligand and stabilized the triphosphate. In the R65 mutant, this distance increased to 4.2+/-0.4A and the interaction energy with the ligand was less favorable, but the K70 epsilon-amino group was repositioned closer to the gamma-phosphate and had a more favorable interaction energy. In the double mutant, E70 could not stabilize the gamma-phosphate, resulting in a more severe defect. The net effect of the atomic-level changes in the double mutant may be to destabilize the pyrophosphate leaving group of the ligand, more severely affecting the catalytic rate of the polymerization reaction than the R65 single mutation.

Increasing prevalence of HIV-1 protease inhibitor-associated mutations correlates with long-term non-suppressive protease inhibitor treatment.

Treatment of human immunodeficiency virus type 1 with protease inhibitors (PIs) is associated with the emergence of resistance-associated mutations. Treatment-characterized datasets have been used to identify novel treatment-associated protease mutations. In this study, we utilized two large reference laboratory databases (>115,000 viral sequences) to identify non-established resistance-associated protease mutations. We found 20 non-established protease mutations occurring in 82% of viruses with a PI resistance score of 4-7, 62% of viruses with a resistance score of 1-3, and 35% of viruses with no predicted PI resistance. We correlated mutational prevalence to treatment duration in a treatment-characterized dataset of 2161 patients undergoing non-suppressive PI therapy. In the non-suppressed dataset, 24 mutations became more prevalent and three mutations became less prevalent after more than 48 months of non-suppressive PI-therapy. Longer durations of non-suppressive treatment correlated with higher PI resistance scores. Mutations at eight non-established positions that were more common in viruses with the longest duration of non-suppressive therapy were also more common in viruses with the highest PI resistance score. Covariation analysis of 3036 protease amino acid substitutions identified 75 positive and nine negative correlations between resistance associated positions. Our findings support the utility of reference laboratory datasets for surveillance of mutation prevalence and covariation.

Pigmentation and microanatomy of skin regenerated from composite grafts of cultured cells and biopolymers applied to full-thickness burn wounds.

Rapid coverage and epithelial closure of extensive burns remains a major requirement for patient recovery. Although many skin substitutes have been described, permanent regeneration of both epithelial and connective tissues after a single surgical application of a skin substitute has not become routine. To replace both dermal and epidermal skin, cultured skin substitutes (CSS) were prepared from autologous keratinocytes and fibroblasts seeded onto collagen-glycosaminoglycan (C-GAG) substrates. CSS were applied to excised, full-thickness burns on 5 patients. Histologic analysis showed a fully stratified, hyperkeratotic epidermis within 12 days of grafting with little to no evidence of an inflammatory reaction. Epidermal and connective tissues are interdigitated in analogy to rete pegs and dermal papillae, and the neovascular plexus approximates the dermal-epidermal junction. Transmission electron microscopy identified a continuous basement membrane with hemidesmosomes and anchoring fibrils that connected the epidermis with the underlying connective tissue. Within 14-28 days, the C-GAG had been degraded and replaced by newly synthesized collagen in regenerated connective tissue. Spontaneous repigmentation of healing CSS from passenger melanocytes in keratinocytes culture was observed within 2 months after grafting. Electron microscopy revealed the presence of numerous melanosomes within the keratinocytes, illustrating pigment transfer between melanocytes and keratinocytes after wound closure. These results demonstrate that the CSS develop into functional permanent skin tissue capable of spontaneous repigmentation after grafting onto burn wounds.

Serious wound infections in burned patients.

Wound infections are a major problem in burned patients. To determine the rate of wound infection associated with initial wound size and the amount of open full-thickness wound, we prospectively studied all patients admitted within 1 week of burn injury during a 2-year period using weekly wound cultures. Wounds were treated with topical silver sulfadiazine and occlusive dressings. Burn wound excision and immediate grafting were initiated during the first postburn week. One thousand five hundred twenty-three patient weeks (483 patients) were evaluated. Serious burn wound infections developed during 55/185 patient weeks (42.3%) when the initial total burn (ITB) was greater than 40% body surface area (BSA). This decreased to 27/304 (8.9%) when the ITB was 21% to 40% and 60/1034 (5.8%) when the ITB was less than 20% BSA. Burn wound infections developed during 57/211 patient weeks (27.0%) when the initial full-thickness burn (IFB) was greater than 20% BSA. The rate of wound infection decreased to 73/776 (9.4%) when the IFB was 1% to 20% and to 12/536 (2.2%) when no IFB was present. We further analyzed the prevalence of serious wound infections in relation to the open wound size during the hospital course. Wound infections occurred during 47 of 96 patient weeks (49.0%) when the current full-thickness wound was greater than 10% BSA. The infection rate decreased to 76 of 594 (12.8%) and 17 of 833 patient weeks (2.0%) when the remaining full-thickness wound was reduced to 1% to 10% and less than 1% BSA, respectively (p less than 0.05). Early wound closure would appear to reduce the risk of serious wound infections, especially in patients with full-thickness burns.

The importance of burn wound size in determining the optimal calorie:nitrogen ratio.

Calorie requirements in hypermetabolic burned patients have been established based on burn size and patient weight. However, the requirement for nitrogen (N), especially with variable open wound sizes, is not clear. Thirty-six adult burned patients were fed with diets containing two different calorie to N (kcal:N) ratios--150:1 (group 1) and 100:1 (group 2)--and N balance was studied with wounds of different sizes. Calorie requirements were calculated with the Curreri formula (25 cal X weight (kg) + 40 Cal X % body surface area [BSA] burned). Daily N balance was calculated from total N intake less total N output (estimated by adding 4 gm to the measured 24-hour urea N production). The data were selected on 233 patient-days when actual calorie intakes were 100% to 150% of the calculated requirement. For a wound size of 1% to 10% BSA, group 1 patients had an N balance of +2.33 gm/day and group 2, +5.54 gm/day. For a wound size of 11% to 30% BSA, N balance was +0.13 and +3.49 gm/day, respectively. For a wound size of 31% to 60% BSA, N balance was -3.38 and +3.88 gm/day, respectively. The traditional 150:1 kcal:N ratio may be adequate for patients with open wounds of less than 10% BSA. Patients with greater than 10% BSA open wounds require a dietary regimen containing a nonprotein kcal: N ratio of 100:1 in order to achieve positive N balance.

Pseudocyst of the pancreas in childhood. Current advances in diagnosis.

A pseudocyst of the pancreas is an uncommon problem in the pediatric patient. When present, more than half of these cases are caused by blunt trauma to the abdomen. Recent experience in the management of three cases demonstrated the importance of sonography in the diagnosis of lesion. Sonography is most effective and noninvasive, and false-positive results are rare. Sonography also was used to follow the progress of a resolving pseudocyst in one of these three cases. A more aggressive surgical approach is necessary in the management of this lesion.

Lack of effect of sleep on energy expenditure and physiologic measures in critically ill burn patients.

OBJECTIVE: Energy expenditure measurements, performed while patients are in standardized resting conditions, are often used as an indicator of care by which to evaluate the adequacy of nutrition support regimens. Little attention has been directed toward examining potential errors incurred by deriving daily energy needs based on a single 15- to 20-minute measurement. This study was designed to differentiate energy expenditure during periods of sleep (defined as time spent in any of the standard sleep stages) and wakefulness in pediatric burn patients. DESIGN: Twenty-four-hour indirect calorimetry, polysomnography, and physiologic assessments (mean arterial pressure, heart rate, body temperature, oxygen saturation, and respiratory rate) were conducted simultaneously in 14 patients, who were thermally injured and tracheally intubated, for a total of 45 24-hour intervals. SUBJECTS: Mean age of the patients was 10.8+/-1.2 years. Mean total body surface area of the injury was 55.7+/-4.7%, and mean full-thickness burn was 48.8+/-6.0%. STATISTICAL ANALYSES PERFORMED: A nested general linear analysis of variance model was used to evaluate the association between sleep, wakefulness, and energy needs; adjustments were made for postburn day and multiple test runs per patient. RESULTS: On average, subjects slept 699+/-46 minutes/day. They experienced a large number of awakenings from sleep (mean=53+/-6.3 awakenings per 24 hours). Patients had mean energy expenditure of 2,529+/-396 kcal/day while awake and 2,360+/-291 kcal/day while asleep, and these mean values did not differ significantly. No differences in physiologic measurements during the awake and sleep states were found. APPLICATIONS: There appears to be little difference in the metabolism of seriously injured burn patients while asleep and while awake. The study deemphasizes the importance of performing indirect calorimetry at rest in critically ill pediatric burn patients, and it supports the extrapolation of daily energy expenditure from a 15- to 20-minute steady-state measurement obtained during either sleep or wakefulness.

Outcome of care. Complications from radiation therapy treatment.

This study was undertaken to examine radiation treatment complications. From September 1987 through December 1989, 29,380 patients were screened at their follow-up visits for possible radiation complications. Of these patients, 1,380 were singled out for further study. These 1,380 charts were examined by a radiation oncologist and physicist to determine if there was a radiation complication, the severity of the complication, and whether a calculation or setup error could account for the complications. Of the 1,380 patients studied, 178 (3% of new patients treated each year) were determined to have radiation complications. These complications were divided into four categories of severity and entered into our computerized tumor registry as follows: complication type R1, complete recovery from symptoms, n = 59; R2, injury requiring medications to control injury, n = 104; S1, surgical intervention for one organ, n = 12; and S2, surgical intervention for two organs, n = 3. We believe that a baseline complication rate of 5% is acceptable in radiation oncology practices. However, the examination and documentation of the outcome of care in the form of radiation complications can help improve patient care and keep the radiation oncologist abreast of treatment outcome trends in the department.

Uninterrupted moderately accelerated radiotherapy in the treatment of unresectable/advanced head and neck cancer: one institution's experience and a comparative review.

Conventional radiotherapy alone in treatment of unresectable or locally advanced head and neck cancer has poor results. To improve outcome without significant increase in acute and late morbidity, we began a moderately accelerated hyperfractionation radiation therapy protocol without breaks for treatment of unresectable/advanced head and neck malignancies. From August 1984 to June 1995, 48 patients with unresectable or advanced carcinoma of the head and neck were treated using a protocol of accelerated hyperfractionation radiation therapy at Kaiser Permanente Medical Center, Los Angeles. Patients were treated twice a day using 150 cGy per fraction, 4 days per week, to a final dose of 60 Gy. Two patients were excluded from this analysis because they did not complete treatment. With a median follow-up of 33 months, 31 (67%) patients have had disease recurrence, 30 (65%) of whom had a locoregional component to their failures. At the last follow-up, 12 patients (26%) were alive with no evidence of disease, 30 patients had died of disease, and 4 had died of intercurrent disease without recurrence. Nine (19%) patients required treatment interruptions averaging 8 days in duration. This accelerated regimen resulted in outcomes similar to those with conventional radiotherapy, most likely because of a conservative total dose. Further refinement of fractionation schedules with potential incorporation of chemotherapy must be investigated.