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Conventional cancer chemotherapy has enjoyed mixed success because it fails to differentiate patients by the unique molecular characteristics of their disease. 

We know that only a fraction of patients respond to first-line chemotherapy, while the efficacy of adjuvant therapy can vary significantly. This is evident in early stage breast cancer, with which only about 10% of women experience recurrence but all receive adjuvant chemotherapy. A better understanding of breast cancer recurrence could spare most women the trouble, expense, and toxicity of chemotherapy, and save the healthcare system billions of dollars per year. 

Biomarkers help in selecting candidates for various cancer treatments, but only a handful of validated drug—biomarker combinations have been approved, most notably Her2-neu, ERCC1, and K-ras for treating with trastuzumab, platinum compounds, and bevacizumab, respectively. The problem with biomarkers is that they test for only one specific therapy. An assay for sensitivity to platinum, for example, says nothing about what other drugs might work. 

Cultured tumor cell sensitivity testing involves culturing fresh tumor cells and testing them against one or more chemotherapy agents, either in vitro or after implantation into test animals. These tests predict resistance to chemotherapy agents, but not sensitivity. That is, they easily eliminate drugs that do not work, but only poorly predict those that do. Poor predictability is a consequence of cells losing the primary tumor’s physical, biochemical, and even genetic characteristics. 

Biomerk Tumorgrafts™ (“tumor xenograft”), under development by 

, represents a dramatic break from the paradigms of correlative biomarker testing and cell- or tissue-based chemotherapy assays. Tumorgrafts involve harvesting tumor tissue from patients through biopsy or surgery and implanting it in immune-incompetent mice. The tumors are “grown” in these animals and re-transplanted to expand the test animal population to dozens or hundreds of mice. I developed Tumorgraft technology along with Manuel Hidalgo, MD, PhD, at the Johns Hopkins School of Medicine. 

A Tumorgraft established in mice provides a living test bed for investigating anti-neoplastic agents and combinations, including experimental agents. 

Grafted tumors growing in test animals retain the salient characteristics of the original human cancer. The animals may be used to screen anticancer drugs and combinations to personalize treatment for the patient donating the tumor tissue, or can serve as screening platforms for new drugs and combinations or for discovering biomarkers for recurrence, toxicology, or treatment efficacy. Unlike cultured tumor cells in vitro or after transplantation into test animals, Tumorgrafts have been shown to predict both resistance and susceptibility to chemotherapy agents, generating data that might take years to otherwise uncover. 

The Tumorgraft platform is not appropriate for every cancer patient. It requires approximately four to six months to generate enough tumorbearing mice to perform studies. A Tumorgraft candidate must therefore be expected to live at least six months. Tumorgraft development and testing is also an expensive process that is not currently covered by insurance. 

The greatest benefit of Tumorgrafts is the potential to discover treatments that work, while sparing patients from toxicities of drugs that will be ineffective in their particular case. In addition to the resulting treatment efficacy, the patient may also be afforded a significant reduction in the costs of care, as well as improvement in quality of life. 

Tumorgrafts have profound implications for drug development and personalized medicine. The high failure rate for new drugs is in part a function of relying too heavily on “generic” subject populations during human clinical testing. Tumorgrafts, when coupled with advanced biomarker and genetic testing, will enable investigators to hone in on cancers that are distinct within their phenotype and accurately match them with the therapy most likely to work. 

In addition to cancer type, stage, origin, patient age and sex, and treatment history, Tumorgraft characterization includes gene expression, mutations, comparative genomic hybridizations, methylation, and analysis of the proteome and microRNA. This opens the possibility for long-term studies of the efficacy of chemotherapy in specific cancer genotypes. A large database correlating molecular data with treatment outcomes might eventually eliminate the need to grow the tumors in mice. 

Tumorgrafts fill a significant unmet need for cancer drug screening. Unlike biomarkers, which test for only one therapy, or assays based on cultured cells, Tumorgrafts are designed to reproduce human disease in a robust animal model. Genomic and proteomic data generated through Tumorgrafts could eventually serve as the ultimate correlate between chemotherapy regimens and cancer, bridging the gap between phenotype and genotype.

Dr. Sidransky is the chairman of the board of directors of Champions Biotechnology, Inc, the Director of the Head and Neck Cancer Research Division at Johns Hopkins University School of Medicine, and a professor of Oncology, Otolaryngology, Cellular & Molecular Medicine, Urology, Genetics, and Pathology at Johns Hopkins University and Hospital. 

Articles

Tumor Xenotransplantation: The Ultimate Testing Platform for Chemotherapy Drugs

The American Society of Hematology held its 50th Annual Meeting in San Francisco in December, hosting more than 21,000 hematologists, clinicians, and scientists from around the world. This grand forum presented a superb educational program, cutting-edge scientific sessions, and peer-reviewed oral and poster presentations about the latest and most exciting developments in scientific research. The following represents just a few of the meeting’s highlights. For more, visit 

http://abstracts.hematologylibrary.org/content/vol112/issue11

Romidepsin Shows Encouraging Activity in Heavily Pretreated Refractory Cutaneous T-cell Lymphoma 

The novel histone deacetylase inhibitor (HDAC) romidepsin showed encouraging activity in treatment-refractory cutaneous T-cell lymphoma in an international, multicenter, open-label, Phase IIb registration trial, according to Youn Kim, MD, Stanford Comprehensive Cancer Center, Stanford, CA. The noteworthy activity of romidepsin, as well as the favorable safety profile for the drug, suggest that it will be further evaluated as a potential treatment for advanced, refractory cutaneous T-cell lymphoma. Vorinostat was the first HDAC inhibitor to be approved for cutaneous T-cell lymphoma. Romidepsin, a potent pan-HDAC inhibitor, is active against multiple HDAC isoforms. The drug has exhibited activity in both cutaneous T-cell lymphoma and peripheral T-cell lymphoma. 

In 72 evaluable patients, overall disease control rate was 78% (overall response rate [ORR] 42%, complete response [CR] 8%, partial response [PR] 33%, stable disease [SD] 36%). An intent-to-treat (ITT) analysis of 96 patients who entered the study (regardless of whether they received treatment) showed an overall disease control rate of 63% (ORR 34%, CR 6%, PR 28%, SD 29%). Romidepsin achieved responses in advanced stage cutaneous T-cell lymphoma; ORR was 48% in patients with  stage > IIB disease, and four of eight patients with  Sezary syndrome achieved PR. Duration of response was noteworthy in these heavily pre-treated patients who received a median of three prior systemic therapies, according to Kim. The median time to disease progression was 8.3 months in the ITT analysis and 17.7 months in 72 evaluable patients. 

Pruritus, as assessed by a decrease in visual analogue scale (VAS) of at least 30mm, was evaluated as a secondary outcome in this trial. The majority of patients experienced relief of moderate or severe pruritus, despite not being given concomitant steroids or antihistamines. Romidepsin improved pruritus in 33 of 52 patients (63%) with  moderate to severe pruritus at baseline: 17 patients who achieved CR or PR and 16 patients who did not achieve overall response. Thus, although a proportion of patients don’t achieve CR or PR on romidepsin, they may achieve symptomatic relief of pruritus. 

Romidepsin was well tolerated by this difficult-to-treat population. Grade 3 or 4 adverse events occurred as single occurrences in 15% of patients. The most common grade 3 or 4 events included fatigue (6%), nausea (2%), diarrhea (1%), and vomiting (1%). The most frequently reported treatment-related events of all grades were nausea (56%), fatigue (30%), vomiting (26%), anorexia (20%), diarrhea (14%), headache (14%), loss of taste (13%), persistent abnormal taste (11%), and thrombocytopenia (10%). The study allayed concern about cardiac toxicity with  an HDAC inhibitor, since minimal or no effect on the QTc interval was observed. 

FCR New Standard of Care for Untreated and Treatment-refractory CLL 

Rituximab added to fludarabine and cyclophosphamide (FCR) represents a new standard of care for previously untreated patients with  chronic lymphocytic leukemia (CLL), as well as those with  relapsed/refractory CLL, according to two large randomized controlled clinical trials comparing FCR to standard chemotherapy with  FC.

The first study (CLL 8) evaluated 817 previously untreated patients with  advanced CLL. About three-quarters were male, about two-thirds were Binet Stage B, and median age was 61 years. First-line treatment with  FCR was superior to FC for response rate and progression-free survival. Patients in the FCR arm had a 44.5% complete response (CR) rate compared with 22.9% in the FC arm (P=.01). The partial response (PR) rate was lower in the FCR arm (3.3% versus 8.8% for FC), which was attributed to the higher CR rate with  FCR. 

“A higher CR translates to longer time to progression,” explained Michael Hallek, MD, of the University of Cologne in Cologne, Germany, who led this trial on behalf of the German CLL Study Group. 

At a median observation time of 25.5 months, median progression-free survival was 42.8 months for FCR versus 32.3 months for FC, a highly statistically significant difference favoring the addition of rituximab (P=.000007). 

FCR was deemed safe. Although a higher rate of neutropenia occurred in the rituximab-containing arm, no increase in the number of infections or other serious side effects were seen in the FCR arm. FCR was well tolerated in physically fit patients who were older than ages 65 or 70 years, Hallek said. Final results of the REACH trail showed that the addition of rituximab to FC extended event-free survival by 10 months, compared with  standard FC for patients with r elapsed/refractory CLL. 

“We consider this a major advance,” said lead investigator Tadeusz Robak, MD, PhD, Medical University in Lodz, Poland. “There is now enough evidence to support use of FCR in untreated and difficult-to-treat patients with  CLL,” said lead investigator Tadeusz Robak, MD, PhD, Medical University in Lodz, Poland. 

REACH was the largest study in relapsed/refractory CLL, enrolling 552 patients from 17 countries in Europe, North America, Australia, and New Zealand. Patients were randomized to three cycles of FCR or FC, then restaged and treated for three more cycles; those with  progressive disease at restaging were dropped from the study. 

FCR doubled the CR rate: 24.3% versus 13% for FC (P=.0007). Median progression-free survival was 30.6 months with  FCR and 20.6 months with  FC (P=.0002). 

The study did not raise any new or unexpected safety concerns related to rituximab. The safety was in line wit hprevious studies of rituximab, Robak said. A slight increase in adverse events was observed with  the addition of rituximab, including febrile neutropenia, infusion-related reactions, benign and malignant neoplasms, and Hepatitis B. Infections were manageable and similar in both arms. 

Four-Drug Combination as Initial Therapy in Previously Untreated Multiple Myeloma 

Noting that various combination regimens of bortezomib, lenalidomide, dexamethasone, and cyclophosphamide have demonstrated substantial activity in previously untreated multiple myeloma, researchers began a randomized, multicenter, three-arm, phase I/ II study to determine whether combining all four agents would show even greater activity. Shaji Kumar, MD, and colleagues presented safety and efficacy data from the phase-I arm of their study, which focused on identifying the maximum-tolerated dose of this combination. 

Twenty-five treated patients (median age, 61 years) received bortezomib 1.3mg/m2, dexamethasone 40mg PO, lenalidomide 15mg PO, and cyclophosphamide 100, 200, 300, 400, or 500mg/m2 PO for up to eight 21-day cycles, followed by bortezomib 1.3mg/m2 for four 42-day maintenance cycles. When required, patients received prophylactic antibiotics, acyclovir, transfusion support, and concomitant anticoagulants. The primary end-point, maximum tolerated does, was the highest dose of cyclophosphamide in combination with  bortezomib —dexamethasone– lenalidomide resulting in ≤1 dose-limiting toxicity in six patients. 

Adverse events notwith standing (constipation [64%], fatigue [60%], and nausea [52%]), hematologic toxicities were acceptable (grade-3 neutropenia [16%], grade-4 [4%], and grade-4 thrombocytopenia [4%]). The researchers reported their preliminary response rates as follows: 100% ≥ partial response, 68% ≥ very good partial response, 32% complete response (CR)/near CR, 28% CR/stringent CR, and 20% stringent CR. 

Overall, concluded Kumar, the four-drug combination was well tolerated, hematologic toxicities were manageable, and the regimen proved feasible and highly active in patients newly diagnosed with  multiple myeloma. Accordingly, enrollment to the phase-II section of the study will proceed. 

Decitabine as Treatment for Elderly Patients with  Acute Myeloid Leukemia 

To determine the morphologic complete response rate in patients age 60 years or older who have newly diagnosed, untreated acute myeloid leukemia (AML)—who were not candidates for standard induction chemotherapy&mdash;researchers conducted a multicenter, open-label, phase- II trial of decitabine, a potent DNA hypomethylating agent approved for the treatment of patients with  all French—American–British subtypes of myelodysplastic syndrome (MDS). Owing to these patients’ comorbidities and poor performance status, it was thought decitabine therapy would be less intense and better tolerated. 

Of the 55 patients enrolled—all of whom received decitabine 20mg/m2 IV over one hour for five consecutive days every four weeks&mdash;most had intermediate (53%) or poor (42%) risk cytogenetics. With  a median time to response of three months, responses were seen in all subgroups of patients (including five of 19 with  previous MDS and five of 23 with  poor-risk cytogenetics). With  one year follow-up, Amanda F. Cashen, MD, and her colleagues determined the patients’ overall median survival to be 9.6 months. 

Compared with  the roughly 20% 30-day mortality rate usually associated with this population when receiving standard induction therapy, patients on this trial experienced that rate at merely 4%. In light of its efficacy and manageable toxicity profile in this small population of elderly patients with AML, an ongoing phase-III survival trial is being conducted in a similar, but larger group of patients with  the disease. 

Bendamustine Plus Rituximab More Tolerable than CHOP Plus Rituximab for Lymphoma 

Mathias J. Rummel, MD, PhD, and colleagues sought to evaluate the effi cacy and safety of the combination bendamustine plus rituximab (B-R), compared with the combination cyclophosphamide-doxorubicin-vincristine- prednisone plus rituximab (CHOP-R) for the first-line treatment of patients with follicular, indolent, and mantle cell lymphomas. As the study’s primary endpoint was event-free survival (EFS), the investigators attempted to show a noninferior EFS for the B-R treatment, which was defined by a less-than-10% difference in EFS between the two comparative arms after three years. 

Patients randomly received rituximab 375mg/m2 (day 1) plus either bendamustine 90mg/m2 (days 1+2) every 28 days or the CHOP course of therapy every 21 days for a six-cycle maximum. Of the 437 evaluable patients, the overall response rate for those receiving B-R was 94%, similar to the 93% achieved by those associated with CHOP-R. Complete response for the group receiving B-R compared similarly to those getting CHOP-R as well (41% vs. 33%, respectively). Fifty-eight cases of progressive or relapsed disease were noted in the B-R group’s follow-up period, compared with 75 in the CHOP-R group. 

The B-R combination is considered noninferior to the standard CHOPR combination and has a better toxicity profile, stated the researchers. Overall, its recipients had lower rates of alopecia (B-R 0% vs. 89% CHOP-R), less infectious complications (B-R 25% vs. CHOP-R 37%), and less hematotoxic incidences (B-R 19% vs. CHOP-R 36%). 

Studies Analyze Deferasirox for Treatment of Patients with Iron Overload 

Several studies presented this year at ASH centered on the use of deferasirox (Exjade) in patients with transfusion-dependent anemias. Maria Domenica Cappellini, MD, and colleagues conducted an analysis of the EPIC study, a large, prospective, multicenter trial, and evaluated the efficacy and safety of fixed starting doses of deferasirox based on transfusion history, with subsequent dose titration based on serum ferritin (SF) trends. 

All study participants had transfusion-dependent anemia and SF levels ≥1000 ng/mL, or <1000 ng/mL with a history of multiple transfusions, and R2 magnetic resonance imaging—confirmed liver iron concentration of >2 mg Fe/g dry weight. The starting dose was deferasirox 20 mg/kg/d for those patients receiving 2–4 blood units/ month; patients receiving more blood transfusions received 30 mg/kg/d, while those receiving less blood transfusions received 10 mg/kg/d. The primary efficacy endpoint was an SF change from baseline at one year. 

Of the 1,744 enrolled participants, many had underlying anemias, including: ß-thalassemia (N = 1,115), myelodysplastic syndromes (N = 341), sickle cell disease (N = 80), aplastic anemia (N = 116) and other conditions associated with anemia (N = 92). Eighty-nine percent (1,555) of the patients started on ≤20 mg/kg/d and 11% (187) started on >20 mg/kg/d. Twenty-four weeks (median) after treatment initiation, 39% of patients had dose increases (range 2—53). Overall, median SF was significantly decreased from baseline by 264 ng/mL after one year (P < 0.0001) at an average actual received dose of 22.2}5.9 mg/kg/d. 

Despite some patients discontinuing because of adverse events (diarrhea, rash, nausea, or abdominal pain), consent with drawal, unsatisfactory therapeutic effect, or other reasons, none of these was considered treatment related and deferasirox was generally well tolerated with a safety profile consistent with previous clinical trials. According to the researchers, this study not only confirms the efficacy of deferasirox to reduce iron load in a wide range of patients who have transfusion-related iron overload, but it also supports the clinical approach to chronically transfused patients by significantly reducing toxic iron that can damage key organs. 

Another analysis of the EPIC study concerning deferasirox was performed by Norbert Gattermann, MD, and fellow researchers to determine the efficacy and safety of the drug to maintain or reduce body iron and SF in patients with myelodysplastic syndrome (MDS). Noting that such patients are susceptible to iron overload from repeated blood transfusions and increased dietary iron absorption, the investigators enrolled 341 patients with MDS who had a median baseline SF of 2730 ng/mL. 

Those patients had a mean transfusion duration of 3.6 years, and received a mean 116.4 mL/kg of blood in the previous year. The mean actual dose of deferasirox over one year of treatment was 19.2}5.4 mg/kg/day. Gattermann and colleagues determined at one year that there was a significant reduction in median SF from baseline (by last observation carried forward: —253.0 ng/mL; P = 0.0019). The median SF (range) ng/mL values at baseline, three, six, nine, and 12 months were 2729.5, 2358.0, 2209.5, 2076.0, and 1903.5, respectively. Like the previous analysis, this one assessed the same AEs that occurred, most of which were mild-to-moderate in severity. 

Gattermann and colleagues determined similar results in their review of the EPIC study; that deferasirox significantly reduced SF levels over one year of treatment in patients who have MDS with iron overload when appropriate dose adjustments are made every three months based on SF trends and safety markers. 

Nadroparin Reduces Thromboembolic Events in Patients Receiving Chemotherapy 

As patients receiving chemotherapy for cancer are known to be at increased risk for thromboembolic events, Giancarlo Agnelli, MD, and colleagues conducted a placebo-controlled, double-blind, multicenter, clinical outcome—based study called PROTECHT. This study, which was designed to evaluate the efficacy of the low molecular weight heparin nadroparin for prophylaxis of such events, had a primary endpoint of the composite of clinically overt venous or arterial thromboembolic events, and a main safety outcome measure of major bleeding. 

Of the 1,166 patients who were randomized, two groups were to receive either subcutaneous injections of nadroparin (3,800 anti-Xa IU once daily) or placebo, which was to start at the initiation of chemotherapy and last throughout the patient’s entire treatment or up to a maximum of four months. With a multitude of cancer types represented (lung, colon, breast, ovary, stomach, rectum, pancreas, head and neck), 1,150 patients received at lease one dose of the study treatment. 

Agnelli noted that 16/769 (2.1%) of patients who received nadroparin and 15/381 (3.9%) of patients who received placebo experienced a thromboembolic event (interim-adjusted P = 0.033). Fifteen of the thromboembolic events occurred in patients with lung cancer (4.0%, nadroparin group; 8.8%, placebo group). Patients with pancreatic cancer experienced an overall rate of thromboembolic events of 7.5%. With  regard to major bleeding, five patients in the nadroparin group (0.7%) and none in the placebo group experienced a major bleeding (P = 0.177). The minor bleeding events were similar in bothgroups: 77 events in 57 patients receiving nadroparin (7.4%) and 38 events in 30 patients (7.9%) receiving placebo. 

In light of these results, the investigators concluded that, whereas nadroparin reduces the incidence of thromboembolic events in patients with cancer who are receiving chemotherapy, future confirmatory studies should center on patients who are at high thromboembolic risk, like those with lung and pancreatic cancer. 

Study Evaluates Eltrombopag for Treatment of Idiopathic Thrombocytopenic Purpura 

Idiopathic thrombocytopenic purpura (ITP) is a blood disorder that occurs fairly commonly in children and adults, with 50—150 new cases per million people each year. Researchers examined how eltrombopag, a first-in-class, oral, small molecule, non-peptide, thrombopoietin receptor agonist, may be used for treatment of ITP. With the RAISE study, investigators used a six-month, randomized, double-blind, placebo-controlled, phase-III study to analyze the efficacy and safety of eltrombopag in previously treated adults with the disease who had platelet counts <30,000/μL. 

Gregory Cheng, MD, and colleagues enrolled 197 patients (eltrombopag 135); and had all patients’ doses individualized according to each person’s platelet response (75 mg once daily or 25 mg once daily or less). With the primary endpoint being the odds of responding during the treatment period for patients getting eltrombopag versus placebo, the researchers determined that those patients who received the drug were eight times more likely to achieve platelet counts of between 50,000 and 400,000/μL during the six-month trial period compared with those patients who received placebo (overall response [95% confidence interval] = 8.2 [4.32, 15.38]; P < 0.001). 

In the group receiving eltrombopag, platelets rose after one week to 36,000/μL and later ranged from 52,000/μL to 91,000/μL for the remainder of the study. Not only did all patients respond to the drug, regardless of their splenectomy status, use of baseline ITP medications, or baseline platelet counts, but much fewer patients treated with  eltrombopag had any clinically significant bleeding compared with those patients who received placebo. Furthermore, more patients receiving the drug stopped or reduced their dosages of their ITP medications compared with placebo (59% vs. 32%, respectively). 

Overall, the RAISE study found long-term eltrombopag therapy success in significantly increasing platelet counts, decreasing bleeding symptoms, allowing for a reduction or discontinuation of baseline ITP therapies, and reducing the use of rescue ITP medications compared with placebo. As it was well-tolerated, with a similar safety profile to placebo, eltrombopag is an important new treatment option for patients with chronic ITP. 

Dexamethasone vs. Dexamethasone and Rituximab for Treatment of Idiopathic Thrombocytopenic Purpura 

In a two-year trial extending from July 2005 through June 2007, researchers conducted an analysis seeking to determine the activity of rituximab in patients with idiopathic thrombocytopenic purpura (ITP) relapsed or refractory to standards treatments. Their prospective, randomized, multicenter, phase-III study compared treatment of patients with previously untreated ITP and a platelet count of ≤ 20 x109/L who received dexamethasone alone (arm A) versus dexamethasone plus rituximab (arm B). 

Arm-A patients received a single course of oral dexamethasone 40 mg (days 1, 2, 3, 4), and arm-B patients received the same as the first group plus IV rituximab 375 mg/m2 (days 7, 14, 21, 28). The primary endpoint of the study was to compare the sustained response (SR), that is, platelet count ≥50 x 109/L at month+ 6 of treatment. Using an intention-to-treat (ITT) and a per-protocol (PP) analysis, Francesco Zaja, MD, and colleagues evaluated 101 patients (arm A, 52; arm B, 49), and 64 patients (arm A, 38; arm B, 26), respectively. (27 pts who began on arm A failed to achieve initial response or SR, so they received salvage treatment with dexamethasone plus rituximab.) 

Patients were systematically followed up on past the sixth month for a median observation period of 18 months (arm A, 12 patients; arm B, 27; salvage therapy, 19). The SR-loss rate (platelets < 50 x 109/L) for these three groups was 25% (3/12), 11% (3/27) and 10.5% (2/19), respectively, and the safety profile was good with no substantial difference between the two arms of randomization. 

Zaja believes the combination of dexamethasone plus rituximab for treatment of patients with ITP improves overall outcome with out worsening the safety profile. The treatment is recommended as a presplenectomy option, especially for those patients with higher risk of complications. It prolonged SR and reduced rates of relapse to the point where it might even suggest a possible curative effect.

Highlights from the 50th Annual Meeting of the American Society of Hematology.

50th Annual Meeting of the American Society of Hematology

Couldn’t make it to the Henry B. Gonzalez Convention Center in San Antonio, TX December 10—14, 2008 for the San Antonio Breast Cancer Symposium (SABCS)? Don’t worry, we’ve got you covered, with highlights straight from the convention center, thanks to our editors, who covered the best of the 2008 SABCS. This year’s symposium, the first SABCS to be presented by the CTRC, AACR, and the Baylor College of Medicine, encompassed “the full spectrum of breast cancer research” and was designed to “facilitate the rapid transition of new knowledge into improved care for breast cancer patients.” 

Early Breast Cancer Patients Live Longer on Sequencing Tamoxifen and Anastrozole Versus 5 Years of Tamoxifen 

Giving tamoxifen for 2 years followed by 3 years of anastrozole (sequencing strategy) improved relapse-free survival and overall survival compared to 5 years of tamoxifen in postmenopausal women with newly diagnosed, hormone-sensitive, early breast cancer, according to analysis of the sequencing arm and the total population in the large, prospective, randomized ABCSG 8 trial.

Although other landmark trials of adjuvant hormonal therapy have confirmed the superiority of aromatase inhibitors (AIs) over tamoxifen in preventing breast cancer recurrence in patients with early breast cancer, ABCSG is the first to show that patients live longer when treated with an AI. “As distinct from other trials, mature data from ABCSG 8 show a high overall survival benefit,” said Raimund Jakesz, MD, Vienna Medical School, Austria, who presented results.

The study enrolled postmenopausal women withlow- to intermediate-risk, estrogen receptor-positive/progesterone-receptor-positive (ER+/ PgR+), ductal cancer grade 1 or 2, and lobular cancer (18%). Dr. Jakesz pointed out that ABCSG 8 had several unique factors compared with other AI trials: including lobular cancer, including women age 80 years and younger, and not allowing chemotherapy.

ABCSG 8 was originally designed to compare tamoxifen for 2 years followed by tamoxifen for 3 years versus tamoxifen for 2 years followed by anastrozole for 3 years. The trial was stopped early in 2004, and women in the tamoxifen alone arm were allowed to cross over to the sequencing arm.

A benefit of sequencing was observed regardless of age, Dr. Jakesz said. “Women with high expression of ER/PgR did particularly well,” he noted. Those with eR+++/PgR+++ enjoyed longer relapse-free survival and overall survival, he noted.

Analysis of 2922 patients (including crossovers to the sequencing arm) showed that sequencing significantly improved relapse-free survival by 21% (P=.038) compared with5 years of tamoxifen regardless of received treatment. Moreover, sequencing tamoxifen followed by anastrozole improved overall survival by 23% (P=.025) compared with5 years of tamoxifen. “Deathwas reduced in women without recurrence as well as those with recurrence,” Dr. Jakesz stated.

Analysis of the total study population of 3714 showed that sequencing therapy with anastrozole improved relapse-free survival by 27% (P=.001) in patients according to actually received therapy, and sequencing improved overall by 22% (P=.032).

The study turned up no new concerns about safety. As in previous trials, more bone and joint pain was reported in patients taking an AI, and more gynecologic symptoms were reported in the tamoxifen group.

Communicating Risk Prediction of Breast Cancer for an Individual Woman an Elusive Goal 

When an individual patient asks a physician, “What is my risk of getting breast cancer,” the physician has little to offer. “For a woman sitting in my office, her risk is either 0 [she won’t get breast cancer] or 100% [she will get breast cancer],” explained JoAnn Elmore, MD, University of Washington, Seattle, WA. “The ideal risk model needs to work well for the individual woman, so we can counsel her, but we have lots of work to do before we have an ideal risk prediction model,” she said.

The Gail model, developed in 1989, is widely used to estimate expected cancer incidence among populations, but not individuals. This model is based on agreed-upon risk factors that include age, age at first period, age at first birth/or nulliparity, number of first-degree relatives with breast cancer, and history of benign atypical hyperplasia of the breast.

“Websites, such as the American Cancer Society, get hundreds of thousands of hits by women attempting to use this model to estimate their risk of developing breast cancer,” Elmore explained.

A study by Rockhill et al. attempted to validate the Gail model in 82,109 women enrolled in the Nurses’ HealthStudy. Over the first five years of the study, about 1000 women developed breast cancer (1.65%). The expected incidence, according to the Gail model, was 1.55%, “so the risk model worked well at a population level,” Elmore said.

The validation study also found, however, that many of the women diagnosed with breast cancer did not turn out to have high risk factors. In fact, 42% had a lower risk level than cancer-free counterparts. “Among 47 women with a high Gail risk score followed for five years, only one will be diagnosed with breast cancer,” she stated. “The Gail model is equivalent to a coin flip for an individual patient,” she said.

Why is it so difficult to develop an ideal risk prediction model? Elmore said that many risk factors are not highly sensitive or highly specific. Moreover, among most women, the risk is too small to be predicted.

Effects of Aromatase Inhibitors and Tamoxifen on Coagulation Factors 

Tamoxifen, long considered the gold standard for treating estrogen-receptor (ER) positive, early-stage breast cancer, is known to increase the risk of thrombotic events (blood clots). This is of particular concern for women who have clotting disorders. Investigations have been ongoing to determine if aromatase inhibitors (AIs), also approved for treating postmenopausal women with eR-positive tumors, similarly increase a patient’s risk for thrombotic events. Data from various studies suggest that although AIs may increase the incidence of thrombotic events in cancer patients, the risk is not as great as it is with tamoxifen.

Researchers in Edinburgh, Scotland, conducted an open, randomized, pharmacodynamic study to determine whether different AIs affected individual blood coagulation factors differently. They also wanted to find out how switching from an AI to tamoxifen might further affect blood coagulation. Investigators recruited 120 postmenopausal women with invasive ER+ breast cancer, described as “otherwise healthy,” and randomized them to receive 16 weeks of adjuvant therapy with either letrozole (Femara), anastrozole (Arimidex), or exemestane (Aromasin). Following the initial 16- week treatment period, all the patients were switched to tamoxifen.

The women’s fasting blood levels were obtained at baseline and remeasured following 12 and then 16 weeks of treatment. Final fasting blood level measures were obtained after 8 months of tamoxifen therapy. Specific coagulation factors analyzed included plasminogen activator inhibitor antigen, von Willenbrand’s Factor (vWF) antigen, antithrombin III (ATIII), protein C, protein S total, protein S free, activated protein C, resistance (APCR), factor VIII, and fibrinogen.

At the outset of the trial, the researchers hypothesized that because AIs reduce the level of circulating estrogens, their effect on coagulation would be either positive or negligible. Instead they found that the AIs did affect coagulation factors, but not all of the AIs affected every factor in the same manner. Results were evaluated using covariate analysis. Researchers determined the following:

• Only minor changes were seen in any coagulation factors for patients who received the nonsteroidal AIs anastrozole or letrozole.

• Exemestane, the only steroidal AI, significantly reduced levels of the anticoagulants protein C and ATIII, which investigators suggested might predispose patients to an increased risk of thromboembolic disease.

• The non-steroidal AIs produced a significant increase in vWF from baseline, but the mean percentage change did not differ significantly from that seen with exemestane.

• The effects of tamoxifen on coagulant levels were significant and complex; tamoxifen significantly decreased levels of protein C and the anticoagulant ATIII, which investigators theorized might “explain the increased risk of deep vein thrombosis observed with this drug.” The agent also caused a significant increase in protein S free.

The authors concluded that AIs and tamoxifen have different but significant effects on coagulation that might account for their association with an increased risk of thrombosis. The more significant effect of tamoxifen on certain coagulation factors might account for its stronger association with thrombotic events.

Alternating Mammography and MRI for Breast Cancer Detection 

Alternating mammography and MRI every 6 months appears to be the best way to detect cancer in high-risk women, an M.D. Anderson study found. This strategy can identify cancers not found by mammography alone, said Huong Le-Petross, MD, assistant professor, Diagnostic Radiology, who presented a retrospective pilot study at a poster session during the San Antonio Breast Cancer Symposium.

“Standard of practice for high-risk women is to perform mammography and MRI every year at the same time. We wanted to see if imaging women every 6 months with alternating modalities would improve detection yield,” she said.

The study was based on a retrospective chart review of 334 women who participated in a high-risk breast cancer-screening program from January 1997 to December 2007 and had one to four MRI screening cycles. Women were deemed high risk if they had hereditary breast and ovarian cancer syndrome, a personal history of breast cancer, a biopsy indicating atypia or lobular carcinoma in situ, or a 20% or higher lifetime risk of developing breast cancer according to the Gail Model.

Of these women, 86/334 (26%) underwent alternate mammography/MRI alternating every 6 months. The other 248 women either had prophylactic mastectomy or initiated chemoprevention strategies. All study participants had a clinical breast exam every 6 months. Median follow-up was 2 years (range, 1-4 years).

Nine cancers were detected in seven of the 86 women (8.1%) who underwent screening MRI (five invasive ductal carcinomas, one invasive lobular carcinoma, and three ductal carcinoma in situ [DCIS]).

Of these nine cancers, five (55%) were found by MRI but not by mammography, three (33%) were found by both modalities, and both mammography and MRI missed one cancer (11%) 1mm in size that was found by mastectomy. Mammography alone did not detect any of these cancers. Of the nine tumors, eight were found by MRI, for a sensitivity of 89%. Mean size of the cancers was 10.4 mm (range, 1 mm to 25 mm).

“MRI identified the majority of cancers, while mammography picked up only three of nine. For five of the eight MRI-detected cancers, the mammogram from 6 months earlier was normal or showed benign findings. The global picture is that MRI can pick up breast cancers that mammography cannot,” Dr. Le-Petross said. Future studies are needed to confirm these findings.

Longer follow-up will be needed to determine whether earlier detection with an alternative imaging strategy will be lifesaving. “We are challenging the gold standard—mammography,” she said.

Accuracy of Oncotype DX Confirmed for Patients with early Stage Breast Cancer 

Treated with aromatase Inhibitors Previous studies have shown that the Oncotype DX Recurrence Score (RS) accurately estimates the risk of breast cancer recurrence in postmenopausal women with a diagnosis of invasive node-negative early stage estrogen-receptor (ER)—positive breast cancer who have undergone treatment with tamoxifen. The Oncotype DX molecular assay also helps clinicians select a chemotherapy regimen most likely to benefit the patient.

With a growing number of studies suggesting aromatase inhibitors (AIs) are superior to tamoxifen as an adjuvant treatment for early stage ER-positive breast cancer, researchers from the Royal Marsden Hospital in London, United Kingdom, decided to find out how Oncotype DX would fare in predicting distant recurrence for patients treated with aIs.

Using Oncotype DX, Mitch Dowsett, PhD, and colleagues from the ATAC Trialists’ Group analyzed tumor samples from 1231 women enrolled in the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial. All the patients had been treated previously for early stage ER-positive breast cancer with tamoxifen or anastrozole monotherapy.

Researchers assessed rates of distant recurrence at 9 years and stratified patients according to the number of disease-affected lymph nodes, which ranged from 0 to >4. A total 872 patients (59%) were node-negative, and 306 (17%) were nodepositive. The remaining 53 patients were node-status unknown. Researchers classified an RS <18 as low risk, 18-30 as intermediate risk, and >31 as high risk. Distant recurrence rates at 9-year follow-up correlated with RS. For node-negative patients with a low-risk RS, 4% developed distant recurrence, as did 12% of those in the intermediate range and 25% with a high-risk RS. Distant recurrence rates were higher for node-positive patients: 17% in the low-risk group, 28% in the intermediate group, and 49% in the high-risk group. Researchers noted that regardless of the RS result, the rate of distant recurrence increased in accordance with the number of positive lymph nodes.

Investigators performed a multivariate analysis, adjusting for tumor size, grade, age, and treatment. Dr. Dowsett said, “Our multivariate analysis confirms that along with other standard measures such as tumor size, Oncotype DX contributes independently to providing a more complete picture of prognosis.” He added that the information provided by Oncotype DX would be useful in helping clinicians make chemotherapy decisions “for both node-negative and node-positive early stage breast cancer patients planned for either anastrozole or tamoxifen treatment.”

In addition to validating the benefit of Oncotype DX in predicting distant recurrence, researchers said they found a lower risk of recurrence in patients treated with aIs regardless of node status. At 5 years, the rate of recurrence was 9.1% in the tamoxifen monotherapy group versus 7.8% for those in the anastrozole group; at 9 years, 15.6% of women who received tamoxifen had experienced recurrence compared with 13.2% of women who took anastrozole.

Dr. Dowsett and associates evaluated the same set of patients using Adjuvant! Online. They concluded that Oncotype DX had “highly statistically significant predictive value for distant recurrence beyond that provided by Adjuvant! Online.”

As the use of AIs continues to expand, clinicians needed an accurate means to predict recurrence risk and help clinicians tailor chemotherapy to their patients with early stage ER-positive breast cancer. Dr. Dowsett said that his team’s study “demonstrated for the first time that RS is an independent predictor of distant recurrence in node-negative and nodepositive hormone-receptor—positive patients treated with anastrozole.”

Highlights from the 31st Annual San Antonio Breast Cancer Symposium.

31st Annual San Antonio Breast Cancer Symposium

Online patient support groups and other health 2.0 resources can be a valuable component of cancer treatment. Rather than being dismissive or suspicious of patients’ attempts to find information and support online, oncologists and their staff should offer guidance and encouragement, and view it as an opportunity to strengthen the physician—patient relationship.  

Guiding a futuristic, humanlike character through a maze, players blast away at deadly enemies, always making sure that their energy levels are high, their defense shields are strong, and they have sufficient stores of ammunition. 

It may sound like a classic shoot-’em-up videogame, until you learn that the player controls a humanoid “nanobot;” that the maze really is the human bloodstream; that the bad guys are cancer cells, bacteria, mouth sores, and neuronal impulses; and that the weapons include radiation guns, chemotherapy, and antibiotic rockets. No, 

 is not your typical videogame. Instead, it is an educational tool aimed at adolescents and young adults with cancer. 

 offers a “digital storytelling” section on its website, with videos from a 2007 meeting of young cancer survivors. The Re-Mission site features a community of players, that includes blogs, message boards, and a “What’s up, doc?” section, where cancer patients can pose questions such as, “Is it safe to play basketball at school next year if I have cancer?” Users can submit artwork and poetry as well. In this sense, the principles behind Re-Mission are similar to those of myriad interactive, health-related websites, where patients have been flocking for support and information about cancer and other serious conditions. 

 study on direct-to-consumer pharmaceutical marketing, released in November 2008, found that as many as 145 million adults in the US had sought health information online in the previous 12 months, and that at least 90 million looked on the Internet for drug information. Of them, 60 million were visiting sites with“health2.0” technologies—interactive or user-generated content such as blogs, support groups, message forums, chat rooms, rating services, and audio/ video postings&mdash;more than double the number of people than a year earlier. 

Meredith Abreu Ressi, Manhattan Research’s vice president of research, says there is a cluster effect around health2.0 applications for people with serious health issues. “The highest correlation is age,” Ressisays. “It really kicks in around age 25.” She sees very active communities for chronic obstructive pulmonary disease, depression, fibromyalgia, and emphysema. With cancer, however, age is less of a factor. “It’s the condition that drives them to online communities,” says Ressi, who adds that patients are particularly likely to seek out advice from the Internet when they are being asked to make difficult decisions. 

The study found that cancer patients who looked for health information online were twice as likely to participate in condition specific online communities as the general population of online health consumers. Manhattan Research also says that more than one-fourth of cancer patients in its study could be defined as health2.0 consumers. 

On December 5, as part of a series called “Second Opinion: Medicine Online,” the CBS Evening News aired a story about how social media are affecting medical treatment and research. The piece featured popular online community 

, and talked about how its policy of making de-identified medical records available—with patient consent&mdash;for research purposes is helping to accelerate drug discovery for ALS. 

PatientsLikeMe and similar sites truly are changing the paradigm in the physician—patient relationship. Following a redesign last summer, consumer health information site 

 now incorporates blogs, multimedia content, and “community” pages for various health and wellness topics, including cancer. The site gets about 3 million unique visitors a month. “It’s an environment where people can get all the information they need on a health condition,” says Wellsphere’s chief information officer and chief medical information officer Geoff Rutledge, MD, PhD. “We view this as a combination of information and support.” Each community has designated “health mavens”—clinicians and patients alike&mdash;to lead discussions and answer questions. “Patients can be an enormous source of support,” according to Rutledge. 

This is particularly true among those who see doctors as authoritarian. “Many patients won’t ask questions such as ‘What are the side effects?’ or ‘How much time do I have to live?’ because they fear they’ll be frozen in their tracks,” says Michael Nissenblatt, MD, associate director of medical oncology at 

, New Brunswick, NJ. “If they can find the information on their own time, it is less likely to be threatening to them.” Nissenblatt says well-educated patients are more likely to mention to him information they have found online, in part because they tend to be less intimidated in front of doctors and are more willing to ask questions. 

Though there is some danger with misinformation, Nissenblatt says the Internet often helps patients “integrate information into their lives in a more rational way.” This is particularly true when they have rare diseases. In many ways, the online information supplements what the doctor tells them, such as with knowing the side effects of various treatments. “Everybody knows about hair loss and vomiting from chemotherapy, but not everybody knows about infections,” Nissenblatt notes. 

Sacramento (CA) Center for Hematology and Medical Oncology

 board member, largely agrees that patients should do whatever they can to learn about and understand their conditions. “My practice certainly encourages it,” Miller says. 

Miller tends to direct patients toward “more mainstream” sites, such as ASCO’s cancer.net (formerly 

. Although he says the ACOR site is “old-school Web 1.0 stuff, it’s a very good resource in terms of tumor type.” 

, tends to prefer condition-specific sites, including the 

 for the rare gastrointestinal stromal tumor (GIST), and various carcinoid support groups. Miller also mentions a few that are specific to certain types of cancer, including the 

. The latter has an ongoing partnership with ASCO. 

Because cancer is such a serious ailment, oncologists naturally see online resources as supplements to, rather than replacements for, professional medical care. The Manhattan Research survey found that 40% of medical oncologists actually went online while consulting with patients to show them some of the available resources. “They’re more likely than other physicians to recommend an online support group,” Ressi says. “That said, oncologists aren’t swayed [by online information] in their decisions.” 

Indeed, Nissenblatt views online support groups and consumer education sites in the same light as treatment guidelines: helpful, but by no means the last word. A computer might guide the doctor toward a prognosis or course of treatment; “however, it doesn’t tell me anything about the human being sitting in front of me,” he says. “There’s no computer that can be compassionate or understanding, or hold my hand, and that’s my job,” Nissenblatt adds. “It is vital to sit down and inform the patient and family of the diagnosis and treatment … in the context of that particular type of cancer.” 

Anna Gottlieb, executive director of cancer support group 

, agrees that there is nothing like some good, old-fashioned face-to- face compassion. “There’s a big difference between getting educational information online and getting social and emotional support,” says Gottlieb, who started the Seattle chapter of the well-known cancer support group in 2002. For this reason, Gilda’s Club has remained a traditional support organization. However, she sees a benefit in the online world as a supplement to in-person meetings and as a way of reaching people in rural areas. “In a city like this, you have an option to do both,” Gottlieb says. “People in smaller towns might not.” And for younger people who essentially were weaned on computers, online support groups might offer an easier path to comfort. “It is hard for people who are diagnosed very young,” Gottlieb says. “They need as much support as they can get.” 

Although doctors certainly do make mistakes, it is important to know that some corners of the Internet are rife with bad or misleading information and hidden agendas. For one thing, Gottlieb says, “You don’t know who you’re talking to.” And often, information is unfiltered and unverified. Nissenblatt often reads consumer cancer sites. “The sites in which no products are being sold are probably more reliable,” he says. He has seen sites that hawk such dubious remedies as intravenous vitamin C, chelation therapy, and even horse urine, which was a widely accepted cancer remedy in the 1950s and ’60s. 

Nissenblatt notes that herbals and other alternative medications are widely used for cancer treatment in Germany. “These things have very little value and many side effects and extreme costs,” he says. Three of his current patients regularly travel to Germany and hear about these options, but they have run the idea by him rather than tried the substances on their own. “If they try to navigate it on their own, they are likely to be misled.” 

, the popular online reference tool that relies on the general public to update and edit its millions of entries. Comedian Stephen Colbert coined the term “wikiality,” a combination of wikiand reality, to illustrate that a falsehood can be taken as fact simply if enough people believe something is true. Kevin Clauson, PharmD, associate professor of pharmacy practice at 

 in Palm Beach Gardens, FL, has studied the accuracy of drug information on Wikipedia. “The onus is on health professionals to recognize its limitations,” Clauson says. 

Clauson led a study that appeared in the December issue of 

, comparing Wikipedia to the free, online 

. The study checked the scope and accuracy of the two reference tools against FDA-approved package inserts from drug manufacturers. “Drug information in Wikipedia has a narrower scope, is less complete, and has more errors of omission than the comparator database,” the article concludes. However, the researchers say Wikipedia showed improvement over time as users fixed earlier shortcomings. “That’s one of the strengths of Wikipedia,” Clauson says: the ability to make quick updates. 

Clauson tells doctors and other practitioners not to just dismiss any information patients bring in from Wikipedia or similar sources. “If you’re going to do that, offer them an alternative,” he advises. On this point, Rutledge agrees. “The unguided exploration of the Internet on medical topics is not nearly as effective as exploration in conjunction with a physician. The real value of the Internet is in conjunction with the doctor,” he says. “Not to diagnose … but to engage the doctor,” Rutledge explains. “It is overwhelming sometimes to go online,” says Gottlieb, and patients need all the help they can get. Physicians just might be uniquely suited to apply their compassionate healing skills to helping their patients navigate the world’s largest storehouse of knowledge and opinion, the Internet.

Neil Versel is a freelance writer and proprietor of 

Is the rising chorus of online opinion good for you and your patients?

Are You Losing Your Voice?

In today’s busy medical practice setting, physicians often fail to communicate everything that patients need or want to know. If verbal instructions are shared, they are readily forgotten. Patient handouts are helpful, but in a 

, 80% of physicians reported doing a “poor” or “very poor” job of distributing handouts during office visits. When patients leave the office with unanswered questions, they naturally turn to the Internet to fill the information gap.

Google, WebMD, and other online resources off er in-depth health information about virtually every possible medical topic. But casual online searches by patients can quickly lead to misinformation, conflicting recommendations, and a general feeling of being overwhelmed.

Patients need information from the source they trust most: their own physician. But most doctors don’t offer patient education information online. Most practice websites are focused on providing administrative information and promoting the physicians and their business. And those practices that have taken the time to publish educational content often find it difficult to maintain.

There are several benefits to having your own patient education resource available online. In a 2007 physician survey distributed by 

48% of respondents stated that having patient education available online reduces phone calls regarding therapy.

57% stated that offering an online educational resource saves time during patient discharge.

67% stated that patient education improves patient satisfaction. 

The educational content you provide on your practice website should cover the conditions you treat, procedures you perform, and medications you prescribe. If you have already created patient handouts, you should make them available online. Your website can also be populated with content from third-party sources that you have evaluated and determined are balanced and reliable. These may include:

• Government agencies (eg, NIH, CDC, NCI, etc)

• Professional medical societies and associations (AAFP, AAP, ACC, ACAAI), many of which now offer basic information about the conditions their members treat. Some have developed more in-depth patient-resources, such as 

 from the American College of Cardiology. • Patient advocacy organizations (eg, AHA, ALA, ACS). These groups often provide practical information about insurance, employment, school, and other lifestyle issues on their sites.

To make your patient educational offering particularly robust, you might consider licensing interactive content from a medical publisher, such as the 

, which sells online presentations and videos.

Or you could try Vivacare, a free patient education service that enables physicians to quickly create their own Web-based patient education library that is preloaded with printable handouts and clinical images. The content can be easily customized to match your specialty and personal approach to care. Topics can be turned on or off, photos can be published, and handouts can be edited or replaced with your own. The library can be integrated into your existing website or serve as the basis of a standalone practice website.

It benefits you and your patients if you can tell them “to learn more about your diagnosis, visit my website.” Patients and their families benefit by gaining convenient access to health information that reinforces what they learned (or should have learned) in your office. They gain a firm grasp of your qualified opinion before going to anonymous websites for second and third opinions. You can strengthen your voice amidst the online noise and have a useful tool that improves clinical care and increases patient satisfaction.

Dr. Becker is a pediatrician and President-founder of 

, which provides medical practices with customizable Web-based patient education services.

	In today’s busy medical practice setting, physicians often fail to communicate everything that patients need or want to know. If verbal instructions are shared, they are readily forgotten. Patient handouts are helpful, but in a 

	Google, WebMD, and other online resources off er in-depth health information about virtually every possible medical topic. But casual online searches by patients can quickly lead to misinformation, conflicting recommendations, and a general feeling of being overwhelmed.

	Patients need information from the source they trust most: their own physician. But most doctors don’t offer patient education information online. Most practice websites are focused on providing administrative information and promoting the physicians and their business. And those practices that have taken the time to publish educational content often find it difficult to maintain.

	There are several benefits to having your own patient education resource available online. In a 2007 physician survey distributed by 

	57% stated that offering an online educational resource saves time during patient discharge.

	67% stated that patient education improves patient satisfaction. 

	The educational content you provide on your practice website should cover the conditions you treat, procedures you perform, and medications you prescribe. If you have already created patient handouts, you should make them available online. Your website can also be populated with content from third-party sources that you have evaluated and determined are balanced and reliable. These may include:

	• Government agencies (eg, NIH, CDC, NCI, etc)

	• Professional medical societies and associations (AAFP, AAP, ACC, ACAAI), many of which now offer basic information about the conditions their members treat. Some have developed more in-depth patient-resources, such as 

	To make your patient educational offering particularly robust, you might consider licensing interactive content from a medical publisher, such as the 

	Or you could try Vivacare, a free patient education service that enables physicians to quickly create their own Web-based patient education library that is preloaded with printable handouts and clinical images. The content can be easily customized to match your specialty and personal approach to care. Topics can be turned on or off, photos can be published, and handouts can be edited or replaced with your own. The library can be integrated into your existing website or serve as the basis of a standalone practice website.

	It benefits you and your patients if you can tell them “to learn more about your diagnosis, visit my website.” Patients and their families benefit by gaining convenient access to health information that reinforces what they learned (or should have learned) in your office. They gain a firm grasp of your qualified opinion before going to anonymous websites for second and third opinions. You can strengthen your voice amidst the online noise and have a useful tool that improves clinical care and increases patient satisfaction.

	Dr. Becker is a pediatrician and President-founder of 

Patients are going online for health information but would prefer to get it from you. Are you there to help them?

Provide Your Patients with an Online Resource You can Both Trust...Your Own!

	How does today’s connected, “always on” world translate to your medical practice? Should you be e-mailing your patients? Performing online consults? Telephone consults? What about telemedicine? The 

 defines telemedicine as “the use of medical information exchanged from one place to another via electronic communications to improve patients’ health status. This includes providing direct patient outreach and services and use of the Internet and other technologies for tele-consultations, patient medical education, remote patient monitoring, online medical records, specialist referrals and much more.”

 that as many as 70% of all doctor visits are for information only or for matters that can be easily handled over the phone. Data shows that more than 36 million Americans have been treated successfully through 

telemedicine, telephone, or e-mail consultations

. In addition, there is also a growing population of patients who can’t travel to the doctor easily, compromising their health and increasing their incidence of medical complications. Therefore, physicians and patients are gradually turning to electronic communication as a supplement to traditional visits. This technological step forward raises concerns about time, cost, liability, privacy, and security, remembering that communications need to be HIPAA compliant. But what if you could set up a system in which patients could receive e-mail and telephone consultations, including diagnosis and treatment for the more minor issues that don’t require office visits? What if for chronic patients you could set up a telemedicine system with secure video visits, with the ability to take vitals, obtain pertinent history, and measure important variables? What would systems that address all these concerns look like? What, if any, are the technical, liability, and ethical issues? “There is a whole move toward consumer-oriented healthcare: Your time, your place, your way,” says Jonathan Weiner, professor of health policy, Johns Hopkins Bloomberg School of Public Health.

	Since a variety of modalities and technologies now make it possible for physicians to exchange information, from brief messages to complete patient records, with each other and with patients—including tools as simple as e-mail and as sophisticated as two-way secure video with biometric patient monitoring&mdash; many physicians are integrating them into their practice. A host of services are becoming available at various levels of service, both to physicians and directly to patients.

	Physician adoption of electronic communication, particularly with their patients, has grown slowly in recent years; an estimated 38% of physicians reported using online communication with their patients in 2008, up from 31% in 2007, and 25% in 2006, according to 

. While the telephone appears to remain the channel of choice for urgent contact, many physicians are discovering that e-mail is a more efficient means for eliminating phone tag and documenting transactions.

	So what services are available? Some physicians have begun to offer patient access via e-mail. Although convenient, e-mail correspondence does raise the concern that a physician won’t be able to respond in a timely fashion to a barrage of messages. Many physician users say this has not been the case and that the bulk of patient correspondence tends to be regarding setting appointments, refilling prescriptions, and transmitting lab results, which would probably have been more time-consuming through traditional methods.

, the number of physicians who offer online patient consultations might increase in the wake of several developments in 2008:

 for online evaluation and management services provided by a physician (formerly Category III CPT Code 0074T.

		Large medical malpractice insurers will offer premium discounts to physicians who e-mail with patients.

How does today's connected, "always on" world translate to your medical practice?

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Provide Your Patients with an Online Resource You can Both Trust...Your Own!

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