Risk of Second Cancer Following Radiation Therapy Is Small

In a study of adults who survived at least 5 years after being treated for solid cancers that are routinely treated with radiation therapy, 9 percent developed a second solid cancer over an average follow-up time of 12 years. About 8 percent of those cancers appear to be related to radiation therapy. Results from the study, led by Dr. Amy Berrington de González of NCI’s Division of Cancer Epidemiology and Genetics, were published online March 29 in Lancet Oncology.

In the first comprehensive analysis of its kind, Dr. Berrington de González and her colleagues examined data from nearly 650,000 adult patients recorded in nine of the Surveillance, Epidemiology, and End Results (SEER) registries between 1973 and 2002. Depending on their initial cancer type, between 23 percent and 79 percent of the patients received radiation therapy during treatment.

The researchers calculated the relative risk of developing a second cancer for patients who received radiation therapy during their initial treatment compared with patients who did not. The relative risk of developing a second cancer associated with radiation varied with type of first cancer and was highest in survivors of testicular seminoma. After adjusting for factors such as age, time since initial diagnosis, and year of diagnosis, the researchers estimated that about 3,300 of the 60,271 second cancers observed over the study period could be attributed to radiation therapy.

The study also described for the first time the overall absolute risk of second cancers related to radiation therapy: an estimated 5 of every 1,000 patients treated with radiation therapy who survive for 15 years would be anticipated to develop a radiation-related cancer. “That number can be used by doctors to convey the message to patients that the absolute risk of developing a second cancer related to radiotherapy is quite small,” explained Dr. Berrington de González.

Further research will be needed to determine the risks from newer radiation therapy technologies, such as intensity-modulated radiation therapy (IMRT), which expose normal tissues to different patterns of radiation than older techniques. Previous studies have raised concerns “that the second cancer risk might be higher in patients treated with IMRT. We will need to study this exposure in the future to assess that risk,” concluded Dr. Berrington de González.

source:NCI bulletin

Test May Detect Mesothelioma at the Earliest Stages

An investigational test based on a panel of 13 protein markers in the blood may be able to detect malignant mesothelioma in people exposed to asbestos, even when the disease is in its earliest stages, according to findings from a study presented at the AACR annual meeting. To conduct the study, researchers used a technology that relies, in part, on DNA molecules called aptamers that bind to proteins in blood samples.

The study used a test developed by Colorado-based SomaLogic (which also funded the study). The test was used to analyze blood samples from 90 patients who had been exposed to asbestos and developed malignant mesothelioma and blood samples from 80 healthy participants who had been exposed to asbestos (control subjects). The research team, led by Dr. Harvey Pass from the New York University Langone Medical Center, used 75 percent of the samples to identify a panel of proteins that were routinely seen in blood samples from patients with mesothelioma but not in samples from the control subjects. Dr. Pass’ laboratory is supported by NCI’s Early Detection Research Network.

The biomarker panel in this “training set” had 80 percent sensitivity and 100 percent specificity for distinguishing between mesothelioma patients and control subjects and detected 15 of the 19 early-stage mesotheliomas, reported Dr. Pass. Similar results were seen in the remaining 25 percent of the samples, known as the validation set. During a press briefing, Dr. Pass also presented data on the test’s performance in a different blinded validation set of samples from 38 patients with asbestos-related mesothelioma and 62 healthy asbestos-exposed control subjects. In this set, the marker panel had 92 percent specificity and 92 percent sensitivity.

In most patients with malignant mesothelioma, the disease is typically diagnosed at an advanced stage, when treatment has very limited success. So the ability to detect early-stage disease is important “because these are the people with mesothelioma who will have long-term survival,” Dr. Pass said during the briefing.

The current incidence of malignant mesothelioma is low: approximately 3,000 cases a year in the United States. However, according to Dr. Pass, an estimated 27.5 million people in the United States alone had occupational exposure to asbestos between 1940 and 1979, and because of its long latency period, the incidence of mesothelioma is not expected to peak for another 20 years.

Additional validation studies of the assay are being planned, Dr. Pass said in an interview, and more aptamers are being added to the test in an effort to improve its performance.

source: NCI bulletin

Aspirin Linked to Lower Pancreatic Cancer Risk

Study Shows Association Between Regular Aspirin Use and Reduced Risk of Pancreatic Cancer


close up of generic aspirin bottle

Preventing pancreatic cancer may be an additional health benefit of using aspirin to treat everyday aches and pains or prevent heart disease.

A new study shows people who took aspirin at least once a month were 29% less likely to develop pancreatic cancer than those who used other types of pain relievers or nothing at all.

Researchers also found people who regularly take low-dose aspirin to reduce their risk of heart disease had a 35% lower risk of pancreatic cancer.

But researchers are quick to point out that aspirin may not be for everyone, and these results need to be confirmed by further studies. The study shows an association but is not designed to show cause and effect.

“The results are not meant to suggest everyone should start taking aspirin once monthly to reduce their risk of pancreatic cancer,” says researcher Xiang-Lin Tan, of the Mayo Clinic College of Medicine in Rochester, Minn., in a news release. “Individuals should discuss use of aspirin with their physicians because the drug carries some side effects.”

Comparing Pain Relievers

The study, presented this week at the American Association for Cancer Research 102nd Annual Conference in Orlando, Fla., examined the relationship between the use of three common types of pain relievers (aspirin, NSAIDs, and acetaminophen) and pancreatic cancer.

Researchers compared pain reliever use in 904 people who had been diagnosed with pancreatic cancer and 1,223 similarly matched healthy adults 55 years or older. The study showed that those who regularly used aspirin were less likely to develop pancreatic cancer.

After adjusting for other factors known to affect pancreatic cancer risk, such as body mass index (BMI) and smoking status, the study showed people who used aspirin at least at least one day during a month had a 29% lower risk of cancer compared with those who did not take aspirin regularly.

Researchers found no association between NSAID or acetaminophen use and pancreatic cancer risk.

source: webMD

Early Initiation of Hemodialysis

One-year mortality was higher with earlier than with later initiation, even in healthier patients.

Recent trends toward early initiation of hemodialysis (HD) — at estimated glomerular filtration rates (eGFRs) >10 mL/minute/1.73 m2 — have been driven by expectations that it would lower early morbidity and mortality in patients with end-stage renal disease (ESRD). Because prior studies were criticized for not controlling for comorbidity, researchers based this study on a U.S. ESRD database of 81,000 HD patients (age range, 20–64) without substantial comorbidities other than hypertension; survival was assessed specifically among the 36,000 “healthiest” patients (those with serum albumin levels 3.5 g/dL).

In analyses adjusted for several clinical and demographic factors in the healthy cohort, death by 1 year was more common among patients who initiated HD at higher eGFRs. For example, compared with mortality in patients who initiated HD at an eGFR <5.0 mL/minute/1.73 m2, mortality was 53% higher for patients with an eGFR of 10.0–14.9 and 118% higher for patients with an eGFR >15.0. These results corroborate those of a recent Canadian study (JW Gen Med Feb 1 2011).

Comment: An editorialist challenges the current clinical focus on initiating HD at the earliest signs of uremic symptoms irrespective of eGFR, because this study and others (including a recent randomized trial; JW Gen Med Jul 22 2010) do not support such an approach. She calls for a more structured assessment of the burden of early uremic symptoms compared to the burdens and potentially higher mortality associated with HD initiation at higher eGFRs.

Source:Journal Watch General Medicine


Telemedicine for Stroke Care: The Finnish Experience

Two-year outcomes support the safety and effectiveness of telestroke.

The Finnish Telestroke Taskforce has established a telemedicine network to assist with acute stroke evaluations. For this study, the taskforce prospectively analyzed the clinical characteristics and 3-month outcomes of patients evaluated via this telemedicine network during a 2-year period. The authors examined outcomes in patients who were evaluated at the single large hub facility and at five community spoke hospitals (all of which have stroke units and thrombolysis services available during regular working hours; telemedicine was used outside of these hours). Follow-up was conducted via in-person or telephone assessment. The investigators used the National Institute of Neurological Disorders and Stroke study definition of symptomatic intracerebral hemorrhage (sICH).

During the study period, telemedicine consultations occurred regarding 106 patients considered potentially eligible for thrombolytic therapy at the spoke facilities. Sixty-one of these patients (57.5%) underwent thrombolysis, a rate higher than in other published telemedicine studies. Reasons for not treating with thrombolysis included mild or resolving symptoms, stroke mimics, large hypodensity on computed tomographic imaging, time since symptom onset greater than the recommended treatment window, multiple potential causes of the stroke, premorbid dependency, severe stroke or NIH Stroke Scale score >25, ICH, elevated blood pressure, or elevated international normalized ratio. After thrombolysis, the sICH rate was 6.7% and 3-month mortality was 11.5%. At 3 months, “good” outcomes (modified Rankin Scale scores [mRS] 0–2) occurred in 49.1% of patients who were treated with thrombolysis at spoke centers and “excellent” outcomes (mRS 0–1) occurred in 29.4% — rates that were comparable to those at the hub (58.1% and 36.8%, respectively).

Comment: Telestroke enables remote stroke practitioners to evaluate patients’ clinical deficits reliably (Class I, Level A) and to render medical decision-making in favor of or against the use of thrombolysis for acute stroke when a bedside practitioner is not immediately available (Class I, Level B; JW Neurology Jul 21 2009). This nonrandomized cohort analysis shows that (1) sustainable telemedicine programs in stroke are feasible, (2) timeframes for acute management are comparable to those for in-person management, (3) high rates of thrombolysis treatment for acute stroke using telemedicine technologies are achievable, and (4) most important, acute stroke treatment guided by telemedicine yields outcomes similar to those of standard bedside evaluations. Although randomized, long-term outcome data are needed, reports such as this help add considerable confidence about the safety and effectiveness of telemedicine for stroke care.

Source:Journal Watch Neurology


Denosumab for Bone Metastases from Advanced Prostate Cancer

Denosumab was superior to zoledronic acid in preventing skeletal-related events.

Advanced prostate cancer is a highly bone-tropic disease, as demonstrated by the fact that >90% of men who die of metastatic prostate cancer have evidence of bone metastases. Administration of zoledronic acid has been shown to reduce skeletal-related events (SREs) compared with placebo in men with metastatic castrate-resistant prostate cancer. However, despite this treatment, SREs continue to occur in mCRPC patients.

Now, an international group of investigators has conducted an industry-sponsored, randomized, double-blind, phase III trial to determine whether denosumab — a human monoclonal antibody that binds to the receptor activator of nuclear factor-B ligand (RANKL), a critical driver of osteoclast formation and function — would be more effective than zoledronic acid for treating bone metastasis from advanced prostate cancer. A total of 1904 mCRPC patients received either denosumab (120 mg subcutaneously) or zoledronic acid (4 mg intravenously) every 4 weeks. Patients also received either intravenous or subcutaneous placebo, as part of the double-dummy study design. The primary endpoint, assessed for noninferiority, was time to first on-study SRE — defined as pathological fracture, radiation therapy, surgery to bone, or spinal cord compression. The same outcome was assessed for superiority as a secondary endpoint.

The median time that patients remained on the study was 12.2 months in the denosumab group and 11.2 months in the zoledronic acid group. The median time to first SRE was longer in the denosumab group than in the zoledronic acid group (20.7 months vs. 17.1 months; P=0.0002 for noninferiority, and P=0.008 for superiority); the median time to subsequent SRE was also longer in the denosumab group. Incidence of adverse events was similar in both treatment groups, except that more patients in the denosumab group experienced hypocalcemia events (13% vs. 6%; P<0.0001). Osteonecrosis of the jaw occurred at low rates in both treatment arms.

Comment: In a previous trial of men receiving androgen-deprivation therapy for nonmetastatic prostate cancer disease, denosumab was shown to be superior to placebo in increasing bone mineral density and reducing incidence of fractures Also, preliminary data from a large randomized study involving men with nonmetastatic disease suggest that denosumab delays the time to development of metastatic disease. Formal presentation of these data is eagerly awaited..

Source: Journal Watch Oncology and Hematology


Prediction of Venous Thromboembolism in Patients With Cancer By Measuring Thrombin Generation: Results From the Vienna Cancer and Thrombosis Study

Patients with cancer are at increased risk of venous thromboembolism (VTE). Laboratory tests measuring the overall thrombophilic tendency might be useful to assess VTE risk. The aim of this study was to investigate thrombin generation, a key process in hemostasis, as predictor of cancer-associated VTE.

Patients and Methods The Vienna Cancer and Thrombosis Study (CATS) is a prospective observational cohort study of patients with newly diagnosed cancer or progression of disease after remission. The study end point is occurrence of objectively confirmed symptomatic or fatal VTE within a follow-up period of 2 years. Thrombin generation was measured with a commercially available assay.

Results One thousand thirty-three patients with malignancies of the breast (n = 151), lung (n = 148), upper (n = 44) and lower gastrointestinal tract (n = 125), pancreas (n = 67), kidney (n = 34), prostate (n = 122), and brain (n = 134) or lymphoma (n = 126), multiple myeloma (n = 26), and other tumor types (n = 56) were observed for a median observation period of 517 days. VTE occurred in 77 patients (7.5%). Patients with elevated peak thrombin (defined as values ≥ 611 nM thrombin, representing the 75th percentile of the total study population) had an increased risk of VTE with a hazard ratio of 2.1 (95% CI, 1.3 to 3.3, P = .002) in multivariable analysis including age, sex, surgery, chemotherapy, and radiotherapy. The cumulative probability of developing VTE after 6 months was significantly higher in patients with elevated peak thrombin than in those with lower peak thrombin (11% v 4%; log-rank test: P = .002).

Conclusion Measurement of thrombin generation may help identify patients with cancer at high risk of VTE.

source: JCO