PFIZER HALTS ENROLLMENT IN LUNG CANCER TRIAL WITH IGF1R ANTIBODY FOR SAFETY REASONS

NEW YORK (Reuters) Oct 09 - Pfizer Inc has halted patient enrollment in a late-stage lung cancer trial of its experimental drug, figitumumab, for safety reasons, the drugmaker said on Friday.

The halt was recommended by independent safety monitors overseeing the study. In their review, the monitors found more serious adverse events, including deaths, with patients receiving figitumumab, the company said.

Pfizer said currently enrolled patients may continue their treatment in consultation with their physicians. As of Sept 30, 681 patients were enrolled in the phase 3 study out of a target of 820, a company spokesman said.

The company said it notified all clinical trial investigators and regulatory agencies and will work closely with the safety monitoring committee on analyzing the data before issuing further guidance.

The enrollment halt is a blow for Pfizer, which is seeking new medicines as many of its top sellers face patent expirations.

FURTHER TESTING IS NEEDED FOR SMOKERS WITH HEMOPTYSIS AND NORMAL X-RAY

NEW YORK (Reuters Health) Oct 09 - Clinicians should continue to evaluate smokers with hemoptysis even if the chest x-ray is normal as nearly 10% of these patients will have malignancy, say researchers from the UK.

Because the optimal strategy for investigating these patients remains unclear, Dr. David C. Currie and colleagues from Mid Yorkshire Hospitals NHS Trust, West Yorkshire, analyzed data from 270 patients with hemoptysis and a normal chest x-ray to see whether further investigations were justified.

Fiberoptic bronchoscopy was performed in 269 patients, and CT was performed in 257 patients, according to the report in the October Thorax.

Twenty-six of these patients (9.7%) were found to have a respiratory tract malignancy, and 9 of these were candidates for radical treatment. Six had curative surgical resection, 1 had radical radiotherapy, and 1 had photodynamic therapy, whereas 1 patient with non-small cell lung cancer refused radical treatment.

This cancer detection rate is similar to the 0-16% rate found in previous studies, the investigators say.

Nineteen of the patients were diagnosed as a result of their fiberoptic bronchoscopy, and 24 of those diagnosed had CT findings suggestive of cancer.

Based on these findings, the researchers conclude that "further investigation of hemoptysis in smokers with a normal chest radiograph is justified regardless of the amount or frequency of hemoptysis. We recommend that these patients are investigated with CT followed by bronchoscopy."

Thorax 2009;64:854-856.

USE THE RIGHT DOSE FOR ELDERLY PATIENTS WITH NSCLC

NEW YORK (Reuters Health) Oct 12 - In elderly patients with advanced non-small cell lung cancer (NSCLC), appropriate chemotherapy yields improved response rates and survival, according to two reports in the October issue of Lung Cancer.

However, the first paper points out, chemotherapy doses in elderly lung cancer patients are often inadequate.

"Unfortunately, (oncologists still hold) the opinion that in the elderly, dose intensity may mean heavy toxicity rather than efficacy, a belief frequently leading to unjustified chemotherapy undertreatment," write Dr. A. Luciani and associates at S. Paolo Hospital in Milan, Italy.

Comorbidities, polypharmacy and compromised organ function reserve can make it difficult to treat these patients, the researchers point out. To determine the association between delivered dose intensity and its effect on clinical outcomes, they studied 107 patients age 70 and older treated between 1998 and 2007.

Their subjects had not previously been treated with chemotherapy for their tumors, which had advanced to TNM stage IIIB or IV. The most common treatment regimens were single agent vinorelbine (47%), single agent gemcitabine (17%) and cisplatin in combination with vinorelbine (11%).

In roughly two thirds of patients, the relative dose intensity (RDI) was less than 80% of the originally planned dose, considered suboptimal for tumor shrinkage.

The overall response rate (partial response plus stable disease) was 55% when the RDI was greater than 80% versus 33% when the RDI was less than 80%. Corresponding median overall survival rates were 10 months versus 7 months (p <>

Multiple regression analysis identified baseline hemoglobin and body mass index as having significant impact on delivered RDI.

Therefore, Dr. Luciani and associates emphasize, "nutritional deficit as well as even mild anemia must be promptly managed in elderly (chemotherapy) candidates."

In the second paper, Spanish researchers report that the benefits of chemotherapy in elderly lung cancer patients are comparable to those for younger patients.

Their conclusion was based on a review of the clinical trials database of the Spanish Lung Cancer Group. Between 1998 and 2005, 1653 patients were treated with chemotherapy in 6 trials. Two hundred eighty (17%) were aged 70 or older.

Treatment was similar between patients younger and older than 70, with similar numbers of cycles and dose intensity.

Furthermore, "There were no statistically significant differences in the distribution of response, disease-free progression, overall survival or the relative survival rates at 1 year or at 2 years between the two groups," report Dr. Mariano Provencio at Hospital Puerta de Hierro in Madrid, and associates.

Time to progression was 4.2 months in the older group and 4.5 months in the younger group, while median survival was 7.5 months and 7.6 months, respectively.

Given the similar response, Dr. Provencio's group counsels physicians that "the choice between the different options must be based on the situation of the patient, performance status, toxicity profile, comorbidity and the patient's own wishes, rather than on chronological age in itself."

Lung Cancer 2009;66:94-96,103-106.

PET AND CT USEFUL FOR N+ MELANOMA PATIENTS

NEW YORK (Reuters Health) Oct 12 - In staging melanoma patients with palpable lymph nodes, 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are equivalent, but FDG-PET detects more metastatic sites, particularly bone and subcutaneous metastases, Dutch researchers report in the October 1st issue the Journal of Clinical Oncology.

Dr. Harald J. Hoekstra of University Medical Centre Groningen and colleagues came to these conclusions after prospectively studying data on 251 patients who underwent both FDG-PET and CT at five centers.

Distant metastases were suggested by FDG-PET in 32% of the patients and by CT in 29%. After correlation with cytology and histology or 6 months of follow-up, results proved correct in 27% of FDG-PET scans and 24% of CT scans.

The article notes that results were correct in 68 of 79 patients (86%) with positive FDG-PET scans and in 61 of 72 (85%) with positive CT scans.

False positive rates were not statistically different between hospitals, according to the researchers.

Significantly more sites were detected with FDG-PET than with CT (133 versus 112). This was particularly the case for bone metastases (27 versus 10) and subcutaneous metastases (11 versus 5).

Treatment changed in 19% of the patients. In most of these cases (79%), therapy was changed on the basis of both scans. Changes were made solely a result of FDG-PET in 17%, and solely a result of CT in 4%.

The researchers also calculated that FDG-PET provided value in addition to that of spiral CT in 17% of patients. Conversely, CT was of additional value in 9% of the patients.

"Due to the improved staging of melanoma patients with lymph node metastases," Dr. Hoekstra told Reuters Health, "surgical oncologists can better select melanoma patients for curative therapeutic lymph node dissection and refer patients with distant disease to a medical oncologist for systemic treatment."

Overall, he concluded, based on FDG-PET, "melanoma patients with lymph node metastases get the best tailored treatment."

J Clin Oncol 2009;27:4774-4780.

NEW DEFINITION FORM METABOLIC SYNDROME

October 12, 2009 — A new joint statement from a number of professional organizations has identified specific criteria for the clinical diagnosis of the metabolic syndrome, tightening up the definition, which previously differed from one organization to the next [1].

The statement, published online October 5, 2009, in Circulation, includes the participation of the International Diabetes Federation (IDF), the National Heart, Lung, and Blood Institute (NHLBI), the World Heart Federation, the International Atherosclerosis Society, and the American Heart Association (AHA) and is an attempt to eliminate some of the confusion regarding how to identify patients with the syndrome.

"This paper represents an attempt to make the definition global," Dr Robert Eckel (University of Colorado, Denver), one of the authors of the new report, told heartwire . "The IDF definition and the [National Cholesterol Education Program Adult Treatment Panel] ATP III definition have been the two that have been utilized most frequently, and now the different organizations--the IDF, the International Atherosclerosis Society, the NHLBI, and the AHA--have all signed on to a single definition. I think that's a step forward in terms of not continuing to confuse people who are working in this field."

Specifically, the new metabolic-syndrome definition streamlines previous differences related to abdominal obesity as defined by measurements in waist circumference. Substantial disparities existed between the previous IDF and the ATP III definitions of what constituted an excessively large waist circumference, by as much as 8 cm between the two groups, but these have been amended. Now, the criteria for elevated waist circumference are based on population- and country-specific definitions, which, although streamlined, do leave some work to be done, said Eckel.

"The problem that still exists is that regional differences around the world may be substantial in terms of what waist circumference confers additional risk for heart disease and diabetes," he said. "The new definition relies on different geographic regions, or different countries, to drill down into their own databases in terms of relating waist circumference to risk." Eckel noted that the IDF previously considered elevations in waist circumference mandatory when defining metabolic syndrome, although the ATP III did not. Now, waist circumference is just one of five criteria that physicians can use when diagnosing the metabolic syndrome. Patients with three of the five criteria--including elevated waist circumference, elevated triglycerides, reduced high-density lipoprotein (HDL)-cholesterol levels, elevated blood pressure, and elevated fasting-glucose levels--are considered to have the syndrome.

Criteria for Clinical Diagnosis of the Metabolic Syndrome

Measure	Categorical cut points
Elevated waist circumference	Population- and country-specific definitions
Elevated triglycerides (drug treatment for elevated triglycerides is an alternate indicator)	>150 mg/dL
Reduced HDL cholesterol (drug treatment for reduced HDL cholesterol is an alternate indicator)	<40>
Elevated blood pressure (drug treatment for elevated blood pressure is an alternate indicator)	Systolic >130 mm Hg and/or diastolic >85 mm Hg
Elevated fasting glucose (drug treatment for elevated glucose is an alternate indicator)	>100 mg/dL

Notably absent from the joint statement is the American Diabetes Association. As reported by heartwire , there are unresolved scientific issues between the ADA and other associations, including the AHA, regarding the metabolic syndrome. Specifically, the ADA, as well as the European Association for the Study of Diabetes (EASD), objected to the manner in which the metabolic syndrome was characterized as a risk factor for heart disease or diabetes, arguing that there was no need to diagnose a patient with the syndrome because emphasis should be placed on aggressively treating the individual risk factors. In 2005, the ADA and EASD issued their own joint statement calling for a critical appraisal of the metabolic syndrome, its designation as a syndrome, and its clinical utility.

To heartwire , Eckel said the IDF, AHA, NHLBI, and others began working on the new metabolic syndrome definition in 2008 and that they simply went ahead without ADA participation. He stressed the metabolic syndrome is not a disease but simply a clustering of risk factors. The original intention of identifying the syndrome was simply to draw clinicians' and the public's attention to the importance of a high-quality lifestyle, and the metabolic syndrome is never meant to be used as a predictor of heart disease or diabetes risk.

HPV VACCINATION NOT COST EFFECTIVE FOR MALES

October 12, 2009 — Vaccinating boys against human papillomavirus (HPV) in addition to girls is not likely to be cost-effective, conclude a new analysis and an accompanying editorial published online October 8 in the British Medical Journal.

Vaccination of girls is already underway in many countries to protect against cervical cancer. Around 70% of cervical cancer is caused by HPV types 16 and 18, and 2 vaccines protect against these: Gardasil (Merck & Co) and Cervarix (GlaxoSmithKline).

Previous studies that have consistently shown that HPV vaccination of preadolescent (12-year-old) girls is cost-effective, and the new analysis agrees, note the authors, Jane Kim, PhD, and Sue Goldie, MD, MPH, from the Department of Health Policy and Management at the Center for Health Decision Science at the Harvard School of Public Health in Boston, Massachusetts.

Vaccination of boys has been proposed to protect against genital warts. Around 90% of genital warts are caused by HPV types 6 and 11, and only Gardasil offers protection against these. There is also an argument that vaccinating boys will improve "herd immunity."

In the United States, this use of Gardasil — i.e., vaccinating boys to protect against genital warts — was recently recommended for approval by a US Food and Drug Administration Advisory Committee, as reported by Medscape Oncology.

However, the new analysis concludes that "including boys in an HPV vaccination program is unlikely to provide good value for resources, compared with vaccinating girls only."

Not Cost-Effective Under Any Scenario

The researchers used a disease-simulation model to process epidemiologic, clinical, and economic data from the United States. By inputting different sets of data into the model, they could envisage various different scenarios, such as the high and low uptake of the vaccine and shorter and longer duration of vaccine protection.

A similar conclusion was reached by 2 other cost-effectiveness analyses, by not a by third. The study that drew contrasting conclusions was supported by Merck & Co (Emerg Infect Dis 2007;13:28-41), manufacturer of Gardasil, notes an accompanying editorial.

The editorial was authored by Philip Castle, PhD, MPH, from the Division of Cancer Epidemiology and Genetics at the National Cancer Institute in Bethesda, Maryland, and Isabel Scarinci, PhD, from the Division of Preventive Medicine at the University of Alabama in Birmingham.

"Only under the most favorable assumptions for the benefits of adding male HPV vaccination to female vaccination did the cost fall below $100,000 per QALY [quality of life-year], the threshold below which an intervention is considered a good economic investment," the editorialist explain.

Under no scenario did the cost of including males in HPV vaccination programs fall below $50,000 per QALY, which is perhaps a "more fiscally responsible threshold, given the need to lower healthcare costs and increase efficiency," they add.

"By comparison, HPV vaccination of 12-year-old girls was always a good health investment," whatever the modeling, the editorial notes.

"Models used to generate cost-effectiveness projections have limitations imposed by the uncertainties about the course of HPV-related disease," the editorialists write. "Nevertheless, the relative benefits of HPV vaccination of females, compared with vaccination of both sexes, is unlikely to differ greatly with fine tuning of the models, and the health implications are clear — good coverage of females obviates the need to vaccinate boys."

The editorialists make one other point. The majority of cervical cancer (>80%) occurs in developing countries and in areas of low resources, which cannot afford or access HPV vaccines. "Targeting young women in these populations for HPV vaccination and screening older women would have a bigger effect on reducing the burden of cervical cancer than widespread vaccination of young men from resource-rich areas," they state.

JAPANESE MIRACLE

Jpn J Clin Oncol. 2009 Oct 6. [Epub ahead of print]

Related Articles, LinkOut

A Case of Bone, Lung, Pleural and Liver Metastases from Renal Cell Carcinoma Which Responded Remarkably Well to Zoledronic Acid Monotherapy.

Miwa S, Mizokami A, Konaka H, Izumi K, Nohara T, Namiki M.

Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Herein, we report a rare case in which bisphosphonate zoledronic acid (ZA) effectively treated not only multiple bone metastases but also lung, pleural and liver metastases from renal cell carcinoma (RCC). Recently, ZA is used to treat skeletal-related events (SREs) such as bone pain caused by bone metastasis from many kinds of cancer. The patient in the present report had multiple bone metastases from RCC. Remarkable improvement of the bone metastasis was observed following treatment with ZA at a dosage of 4 mg administered once every 4 weeks. Moreover, lung, pleural and liver metastases also diminished markedly in size in response to the treatment. The metastases have shown no progression for 20 months since starting the ZA treatment. We believe that the present report is the first of its kind announcing that ZA monotherapy has been effective for lung, pleural and liver metastases from RCC.

H1N1 EPIDEMIOLOGY

October 12, 2009 — H1N1 critical illness mostly affects young patients and is often fatal, according to the results of Canadian and Mexican studies and an editorial published online October 12 in the Journal of the American Medical Association (JAMA).

"Between March and July 2009, the largest number of confirmed cases of 2009 influenza A(H1N1) infection occurred in North America," write Anand Kumar, MD, from the Health Sciences Centre and St. Boniface Hospital in Winnipeg, Manitoba, Canada, and colleagues with the Canadian Critical Care Trials Group H1N1 Collaborative.

The goal of this prospective observational study was to evaluate clinical characteristics, treatment, and outcomes of critically ill patients who had 2009 influenza A (H1N1) infection in Canada. Between April 16 and August 12, 2009, 168 critically ill patients with 2009 influenza A (H1N1) infection in 38 adult and pediatric intensive care units (ICUs) in Canada were followed up for 28-day and 90-day mortality. Secondary study endpoints included frequency and duration of mechanical ventilation and duration of ICU stay.

Of 215 patients with critical illness, 162 had confirmed, 6 had probable, and 47 had suspected community-acquired 2009 influenza A (H1N1) infection. Mean age was 32.3 ± 21.4 years in the 168 patients with confirmed or probable 2009 influenza A (H1N1); 113 patients (67.3%) were women and girls, 50 patients (29.8%) were children, and 43 patients (25.6%) were aboriginal Canadians.

Among critically ill patients, overall 28-day mortality was 14.3% (95% confidence interval [CI], 9.5% – 20.7%), and shock and nonpulmonary acute organ dysfunction were common (sequential organ failure assessment mean score 6.8 ± 3.6 on day 1). At 90 days, overall mortality was 17.3% (95% CI, 12.0% – 24.0%; n = 29).

At ICU admission, all patients were severely hypoxemic (mean ratio of partial pressure of oxygen in arterial blood [PaO₂] to fraction of inspired oxygen [FIO₂] of 147 ± 128 mm Hg). Median time from symptom onset to hospital admission was 4 days (interquartile range [IQR], 2 – 7 days) and from hospitalization to ICU admission was 1 day (IQR, 0 – 2 days).

Most critically ill patients received neuraminidase inhibitors (n = 152 [90.5%]) and mechanical ventilation (n = 136 [81.0%]). Median duration of ventilation was 12 days (IQR, 6 – 20 days) and of ICU stay was 12 days (IQR, 5 – 20 days). Some patients also required lung rescue therapies, including neuromuscular blockade in 28% of patients, inhaled nitric oxide in 13.7%, high-frequency oscillatory ventilation in 11.9%, extracorporeal membrane oxygenation in 4.2%, and prone positioning ventilation in 3.0%.

"Critical illness due to 2009 influenza A(H1N1) in Canada occurred rapidly after hospital admission, often in young adults, and was associated with severe hypoxemia, multisystem organ failure, a requirement for prolonged mechanical ventilation, and the frequent use of rescue therapies," the study authors write. "Our data suggest that severe disease and mortality in the current outbreak is concentrated in relatively healthy adolescents and adults between the ages of 10 and 60 years, a pattern reminiscent of the W-shaped curve previously seen only during the 1918 H1N1 Spanish pandemic."

Limitations of this study include focus on severe disease requiring ICU admission, possible late deaths occurring after the observation period, and possible overrepresentation or underrepresentation of certain comorbidities and clinical features.

"We have demonstrated that 2009 influenza A(H1N1) infection–related critical illness predominantly affects young patients with few major comorbidities and is associated with severe hypoxemic respiratory failure, often requiring prolonged mechanical ventilation and rescue therapies," the study authors conclude. "With such therapy, we found that most patients can be supported through their critical illness."

Mexican Study

The goal of the second observational study was to describe baseline characteristics, treatment, and outcomes of critically ill patients with confirmed, probable, or suspected 2009 influenza A (H1N1) in 6 Mexico hospitals. Between March 24 and June 1, 2009, the investigators collected demographic data, symptoms, comorbid conditions, illness progression, treatments, and clinical outcomes from 58 critically ill patients with 2009 influenza A (H1N1). The main study endpoint was mortality, and secondary endpoints were rate of 2009 influenza A (H1N1)–related critical illness and mechanical ventilation and length of stay in the hospital and ICU.

Of 899 patients hospitalized with confirmed, probable, or suspected 2009 influenza (A) H1N1, 58 (6.5%) were critically ill. All presented with fever, and 57 of 58 presented with respiratory symptoms; median age was 44.0 years (range, 10 – 83 years). Although comorbid respiratory disorders occurred in few patients, 21 patients (36%) were obese. Median time from hospital to ICU admission was 1 day (IQR, 0 – 3 days). Mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia was needed in 56 of 58 patients. Median day 1 ratio of PaO₂ to FIO₂ was 83 mm Hg (IQR, 59 – 145).

Mortality by 60 days was 41.4% (24 deaths; 95% CI, 28.9% – 55.0%), with 19 deaths occurring within the first 2 weeks. Factors associated with mortality were greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. Neuraminidase inhibitor treatment (vs no treatment) was associated with better survival, after adjustment for a reduced opportunity to receive neuraminidase inhibitors among patients dying early (odds ratio, 7.4; 95% CI, 1.8 – 31.0).

"Critical illness from 2009 influenza A(H1N1) in Mexico occurred in young individuals, was associated with severe acute respiratory distress syndrome and shock, and had a high case-fatality rate," write Guillermo Domínguez-Cherit, MD, from Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán," Mexico City, and colleagues. "Fever and respiratory symptoms were harbingers of disease in almost all cases. There was a relatively long period of illness prior to presentation to the hospital, followed by a short period of acute and severe respiratory deterioration."

Study limitations include relatively early examination of the epidemiology of a severe infectious disease with possible overestimation of case-fatality rate.

"Early recognition of disease by the consistent symptoms of fever and a respiratory illness during times of outbreak, with prompt medical attention including neuraminidase inhibitors and aggressive support of oxygenation failure and subsequent organ dysfunction, may provide opportunities to mitigate the progression of illness and mortality observed in Mexico," the study authors conclude.

In an accompanying editorial, Douglas B. White, MD, MAS, and JAMA Contributing Editor Derek C. Angus, MD, MPH, from the University of Pittsburgh School of Medicine in Pennsylvania, note that many US hospitals may be inadequately staffed to provide treatment of the most seriously ill patients with 2009 influenza A (H1N1) in a timely fashion.

"Hospitals must develop explicit policies to equitably determine who will and will not receive life support should absolute scarcity occur," Dr. White and Dr. Angus write. "Any deaths from 2009 influenza A(H1N1) will be regrettable, but those that result from insufficient planning and inadequate preparation will be especially tragic."

The Canadian Public Health Agency of Canada, the Ontario Ministry of Health and Longterm Care, the Heart and Stroke Foundation Canada, and the Canadian Institutes of Health Research supported the Canadian study. The authors of both studies have disclosed no relevant financial relationships.

JAMA. Published online October 12, 2009.

H1N1 EPIDEMIOLOGY

October 9, 2009 — The reported number of children younger than 18 years who have died from H1N1 influenza in 2009 since April reached 76 this week, which is close to the number of children who normally die each year from seasonal influenza, an official from the US Centers for Disease Control and Prevention (CDC) said today, but the H1N1 virus in 2009 has yet to run its course.

"It's only the beginning of October," said Anne Schuchat, MD, director of the National Center for Immunization and Respiratory Diseases at the CDC in a press conference. "It's hard to predict what will happen next, but we're pretty sure that [the H1N1 virus] will be here going forward. Unfortunately, we do expect more illness, hospitalizations, and deaths in the weeks ahead, particularly among pregnant women and children."

This week the CDC received reports of 16 children dying from confirmed cases of the H1N1 virus and 3 children dying from likely cases. Dr. Schuchat said the pediatric death rate is climbing again after peaking during the spring, followed by a dip during the summer.

The majority of children who have died have had underlying diseases that put them at risk for influenza-related complications, she said, but between 20% and 30% of these children were healthy.

In comparison, the number of children who have died each year from complications of seasonal influenza has ranged from 46 to 88 during the past 3 years, according to Dr. Schuchat.

New Studies Focus on Vulnerability of Children

The risk faced by children in the H1N1 pandemic was underscored by a study published online October 8 in the New England Journal of Medicine. Researchers, including some from the CDC, studied 272 patients who were hospitalized this spring with H1N1 influenza. Of those patients, 45% were younger than 18 years and 5% were older than 65 years.

Further stoking concern about protecting children from the H1N1 virus was a CDC report released today showing that 20.8% of children aged 5 to 17 years were vaccinated for seasonal influenza during the 2008–2009 influenza season. Public health authorities want to see higher immunization rates than this for the H1N1 vaccine, as well as its seasonal counterpart.

However, the public is still getting used to the idea of routine vaccinations for these children. Until 2008, the Advisory Committee on Immunization Practices, an expert panel that advises the Department of Health and Human Services and the CDC, had not recommended annual vaccinations for seasonal influenza for this age group. In 2008, however, the ACIP said that these children should begin receiving the vaccine, beginning in the 2008–2009 season.

Clinicians Can Vaccinate Nonpriority Patients if Vaccine Supply Is Adequate

The national effort to vaccinate children and the rest of the population against the H1N1 virus began this past Monday, just 5 days ago. As of yesterday, vaccine manufacturers had 6.8 million doses available for distribution, and state and local public health authorities had placed orders for 3.7 million doses, said Dr. Schuchat, adding that there is usually a lag between the 2 numbers.

The initial scarcity of the vaccine has prevented states from immediately conducting school-based immunization programs that would reach the vulnerable pediatric population, she said. "We don't have enough for a large-scale rollout." She predicted that as vaccine production ramps up, "we'll be in good shape in the weeks ahead." The CDC has projected that between 40 and 50 million doses of vaccine will be on hand by mid-to-late October.

Anticipating shortages of the H1N1 vaccine, the CDC has recommended that clinicians first immunize a priority group of patients that consists of pregnant women, individuals who live with or care for children younger than 6 months, healthcare workers in direct contact with patients, children aged 6 months through 4 years, and children aged 5 through 18 years with a chronic illness. There is no recommended order of priority within this group.

However, on Thursday the CDC issued guidance for clinicians that would give them the green light to immunize patients who do not belong to this priority group if they have an ample supply of the vaccine.

CDC recommendations on who should be first in line "are not intended to deny 2009 H1N1 vaccine to anyone who wishes to be vaccinated," the agency stated. "However, until local supply of, and demand for, 2009 H1N1 flu vaccine balances out, the decision regarding who should get vaccinated is one that should be made between the provider and the patient, weighing whether there are enough doses available for those at greatest risk for infection and serious complications as well as the likelihood that patients turned away will come back for vaccine at a later date."

N Engl J Med. Published online October 8. Article

YOU CAN IMAGINE WHAT HAPPENS TO GREECE

October 10, 2009 — The US Food and Drug Administration (FDA) is reporting cases of radiation overexposures during brain perfusion computed tomography (CT) imaging. The overexposures took place at a single institution but may reflect a more widespread problem regarding CT quality assurance programs.

During an 18-month period, the agency found that 206 patients received radiation doses that were approximately 8 times the expected level.

According to an alert sent yesterday from MedWatch, the FDA's safety information and adverse event reporting program, "If patient doses are higher than the expected level, but not high enough to produce obvious signs of radiation injury, the problem may go undetected and unreported, putting patients at increased risk for long-term radiation effects."

Patients received 3 to 4 Gy instead of the expected 0.5 Gy (maximum) to the head, the FDA notes. "In some cases, this excessive dose resulted in hair loss and erythema."

The FDA is encouraging facilities that use CT imaging to monitor the dose indices displayed on the control panel, including the volume computed tomography dose index (in units of mGy) and the dose-length product (in units of mGy-cm). Values displayed should be within the range normally used with the protocol. Values should be confirmed again after the patient has undergone the procedure.

Clinicians suspecting reportable adverse events associated with CT devices should follow the reporting procedure established by their facility.

The FDA is collecting more data on this issue and will provide this information as it becomes available.

More information is available on the FDA's MedWatch Web site.

Suspected radiation overexposure after CT should be communicated to the FDA's MedWatch reporting program by telephone at 1-800-FDA-1088, by fax at 1-800-FDA-0178, online at http://www.fda.gov/medwatch, or by mail to 5600 Fishers Lane, Rockville, Maryland 20852-9787.

EXERCISE LOWERS RISK OF BREAST CANCER

October 9, 2009 — Postmenopausal women who maintain a regular, moderate to vigorous exercise program reduce their risk for breast cancer, even if they did not exercise in the past, according to a study published online October 1 in BMC Cancer.

"Among the few modifiable risk factors for breast cancer, a high versus low level of physical activity has been consistently associated with 20-40% reduced risk of postmenopausal breast cancer," write Tricia M. Peters, MPhil, of the National Cancer Institute in Bethesda, Maryland, and colleagues of the National Institute of Health-American Association of Retired Persons Diet and Health Study. "In order to better characterize the physical activity-breast cancer relation, further investigation of specific parameters of physical activity such as the intensity and the time of life of physical activity that may be most effective for breast cancer prevention among postmenopausal women is needed."

The study, begun in 1995, consisted of 118,899 women, ages 50 to 71 years, who answered questions about their exercise habits during 4 periods of their lives: ages 15 to 18 years, 19 to 29 years, 35 to 39 years, and in the past 10 years. Participants also indicated the number of hours exercised per week, from less than 1 to more than 7, and whether their activities were light (eg, bowling and fishing) or moderate to vigorous (eg, jogging and swimming) for each of the periods.

During 6.6 years of subsequent tracking, 4287 breast cancers, mostly estrogen receptor (ER)–positive (84%; n = 1352), were diagnosed among the participating women.

Researchers found that women who maintained a high level of activity for more than 7 hours a week during the 10 years before the study reduced their risk for breast cancer by 16% vs more sedentary women in age-adjusted and multivariate (each relative risk [RR], 0.84; 95% confidence interval [CI], 0.76 - 0.93) models. Adjustment for light exercise during the recent decade did not significantly affect the risk (RR, 0.85; 95% CI, 0.76 - 0.95). Further adjustment for body mass index (BMI) had limited impact on the correlation between brisk activity and the risk for breast cancer (RR, 0.87; 95% CI, 0.78 - 0.96).

The authors noted that their results regarding physical activity after menopause are consistent with previous findings. "Our observation that recent physical activity showed a stronger inverse association with breast cancer risk than historical activity is supported by two systematic review and three prospective studies among postmenopausal women," they point out, citing a review published in Epidemiology (2007;18:137-157) and a cohort study in the Journal of the American Medical Association (2003;290:1331-1336), among others.

Combined light and moderate to vigorous exercise across the lifespan somewhat affected risk (P = .49 -.53). A greater positive relationship between risk and all activity, regardless of intensity level, existed for ages 19 to 29 years and ages 35 to 39 years (P = .79 for both light and moderate to vigorous activity) vs light and moderate to vigorous exercise during the 10 years before the study or for the 15- to 18-year-old period (P = .35 for light activity; P = .28 for moderate to vigorous activity).

Reasons for the link between activity and reduction of breast cancer risk may include the ability of exercise to reduce levels of endogenous sex hormones, modulate insulin and insulin-like growth factors, increase immunity, and reduce ongoing inflammation, according to the researchers.

One limitation of the study was a relatively low response rate by the 3.5 million members of the American Association of Retired Persons who initially received the questionnaires. The authors also note that subjects' ability to remember physical activity that occurred 10 years ago vs in the more distant past may have colored the results. They point out that future studies of lifelong physical activity are needed to verify their findings and provide more details about how exercise intensity and timing affect breast cancer risk.

"Although controlled trials or intervention studies are the ideal study designs for disentangling the 'dose' of physical activity that may influence breast cancer risk, the cost and duration of such studies for researching the association of physical activity intensity and timing with primary breast cancer limits their feasibility," the authors write. "However, interventions and experimental research will be imperative to investigate the mechanism by which physical activity intensity and timing influence breast cancer risk."

The Intramural Research Program of the National Institutes of Health, National Cancer Institute supported this study. The study authors have disclosed no relevant financial relationships.

BMC Cancer. Published online October 2, 2009. Abstract