TROPONIN T AND MORTALITY AFTER PULMONARY EMBOLISM

NEW YORK (Reuters Health) Dec 24 - Elevated troponin T levels in patients with pulmonary embolism are associated with higher in-hospital and 1-year mortality, according to a report in the European Respiratory Journal for December.

A recent meta-analysis suggested an association between mortality and plasma levels of troponins in patients with acute pulmonary embolism, the researchers explain, but the predictive value of elevated troponins for adverse outcomes has remained unclear.

Dr. Karin M. Janata from the Medical University of Vienna, Austria, and colleagues investigated the relationship between troponin T (TNT) and survival in 737 patients diagnosed with pulmonary embolism.

During 1 year of follow-up, 44 (29%) of the TNT-positive patients died, compared with 42 (10%) of the TNT-negative patients.

The in-hospital death rate was 21% among TNT-positive patients, the authors report, but only 6% among TNT-negative patients.

For patients who survived the initial hospitalization, 1-year mortality was 10% in TNT-positive patients versus 5% in TNT-negative patients.

TNT independently predicted mortality after adjusting for cancer, immobility, and age, the investigators say, and after exclusion of initially hemodynamically unstable patients.

"Elevated TNT levels meant a four-times higher risk of in-hospital death and a three-times higher risk of 1-year mortality, even after adjustment for the other most important risk factors of death in this population," the authors report.

Although researchers should perform more trials to determine whether TNT-positive patients could benefit from thrombolysis, the authors conclude, TNT has the advantage of being an objective measure for a condition marked by "soft" subjective parameters.

Eur Respir J 2009;34:1357-1363.

CANCER MORTALITY TRENDS IN EUROPE

December 31, 2009 — New figures for cancer mortality rates in Europe for 2000 to 2004 show "persistent favourable trends over the last years," according to a report published online in the November 30 Advance Access issue of the Annals of Oncology.

Overall cancer mortality rates in the European Union decreased by 9% in men and 8% in women from 1990 to 1994 and from 2000 to 2004.

These decreases are comparable in magnitude to those observed in the last decade in the United States (–0.8% per year in men, –0.4% per year in women) and are similar to those seen in Japan, say the study authors.

Led by Carlo La Vecchia, MD, head of epidemiology at the Mario Negri Institute for Pharmacological Research in Milan, Italy, the team of authors comments that the favorable trend of decreasing cancer mortality rates was seen in all European countries, with the sole exception of Romania.

However, there remains an approximately 2-fold difference in cancer mortality rate (as well as incidence) across European countries. For men, the highest mortality rates were seen in Hungary, the Czech Republic, and Poland, whereas the lowest rates were in Sweden, Finland, and Switzerland. For women, the highest mortality rates were seen in Denmark, Hungary, and Scotland, and the lowest were seen in Spain, Greece, and Portugal.

These differences between the sexes reflect, in part, the different spread of cigarette smoking among men and women across various European countries, the study authors comment. Smoking had declined substantially among men during the last few decades but has increased among women in several countries, they note.

Cancers Linked to Tobacco and Alcohol

These trends in smoking have influenced the patterns seen for several cancers, most noticeably lung cancer. In the European Union as a whole, the lung cancer mortality rate has been declining in men (decreasing by 17% from the late 1980s to the early 2000s), but has increased in women (by 27% during the same period).

A similar, though less pronounced, pattern was seen for oral cancer. Overall, the mortality rate from oral cancer declined by approximately 10% from 1990 to 1994 and from 2000 to 2004, but increased mortality rates were seen in women.

However, mortality rates from oral cancer have also been influenced by changing patterns of alcohol consumption. Together, tobacco and alcohol are associated with more than 80% of cases of cancer of the oral cavity and pharynx, the study authors point out.

Countries such as France and Italy, which had the highest rates of drinking up to the 1980s, have seen a substantial reduction in alcohol consumption in the last few decades. They have also seen a reduction in mortality rates from oral cancer since the mid to late 1980s.

In contrast, alcohol consumption has been increasing in most countries from northern Europe, and the trends for oral cancer here are less favorable, the study authors comment. In particular, the highest rates of mortality from oral cancer were seen in Hungary and Slovakia, and this trend may point to a specific role of fruit-based alcoholic drinks that are popular in these areas, they suggest.

These trends in alcohol consumption have also influenced patterns in mortality from liver cancer. France and Italy had some of the highest mortality rates from primary liver cancer, but these have been decreasing in recent years, mainly because of the reduction in alcohol consumption in these countries since the early 1980s, the authors note. In contrast, mortality rates for liver cancer have been increasing in several central and northern European countries, reflecting the recent increase in drinking there, they add.

Esophageal cancer is also strongly associated with tobacco and alcohol use, and the patterns for this cancer are similar to those for oral cancer, at least in part. As for oral cancer, in the last decade, mortality rates for esophageal cancer were substantially decreased in France, Italy, and Spain, following the decline in alcohol consumption in these countries and a decline in smoking among men. In contrast, the esophageal cancer mortality rate has increased in most northern, central, and eastern European countries.

However, part of the increase in northern Europe is because of an increase in esophageal adenocarcinoma, which is related to obesity, as well as to gastroesophageal reflux disease and tobacco (but not alcohol) use. "Therefore, at least part of the rise in esophageal cancer mortality in northern Europe can be attributed to increased prevalence of obesity," the authors comment.

Factors Influencing Mortality Rates

For several individual cancers, the authors highlight factors that have contributed to the decline seen in mortality rates.

Mortality rates for gastric cancer declined by approximately 30% in both sexes from 1990 to 1994 and from 2000 to 2004. This is attributed to improved diet, diet variety, and food conservation, as well as a decline in the prevalence of Helicobacter pylori infection in more recent generations.

Mortality rates for breast cancer declined by 13% from 1990 to 1994 and from 2000 to 2004, and the variation in rates across Europe was relatively limited. Breast cancer mortality rates have been declining substantially in the last 2 decades in western Europe, the authors note. Improved treatment through antiestrogens and chemotherapy has played a major role, but a favorable impact from screening mammography is also likely in recent years, they comment.

Mortality rates for prostate cancer showed a modest 4% decline from 1900 to 1994 and from 2000 to 2004. Both in western Europe and in the United States, peak mortality rates for prostate cancer were observed in the 1990s, with a levelling off thereafter, the authors comment. This trend likely reflects a favorable impact of advances in treatment, such as androgen deprivation therapy, wider adoption of radical prostatectomy in the elderly population, and radiotherapy for patients with locally advanced disease, they suggest. Less likely to have had an impact is the introduction of prostate-specific antigen testing, they add.

Testicular cancer mortality rates have declined steadily, with a decrease of 26% seen between 1990 and 1994 and 2000 and 2004. This follows a favorable trend observed since the 1970s, which was, however, delayed vs that observed in the United States, the authors comment. Adoption of standard therapeutic protocols has played a role, they suggest.

Testicular cancer is one of the most curable neoplasms if adequate treatment is adopted, they point out. However, such treatment involves platinum-derived chemotherapy and other expensive drugs, and the inadequate availability of these therapies accounts for the smaller decline seen in eastern European vs western European countries, and also in Latin America vs the United States.

"Widespread adoption of efficacious therapy is therefore a priority to avoid unnecessary deaths from testicular cancer worldwide," Dr. La Vecchia and colleagues comment.

The study authors have disclosed no relevant financial relationships.

Ann Oncol. Published online November 30, 2009. Abstract.

COLONOSCOPY REDUCES LEFT SIDE CANCER RISK

December 30, 2009 — Another study of colonoscopy screening in the community setting has shown that it does reduce the risk for colorectal cancer, but this reduction is seen only for left-sided, not right-sided, colorectal cancer.

The latest findings come from Germany, from a study of 3287 participants, and are published online December 30 in the Journal of the National Cancer Institute.

Advanced colorectal cancer was detected by colonoscopy in 36 (6.1%) of 586 participants who had undergone a previous colonoscopy in the preceding 10 years vs 308 (11.4%) of 2701 participants with no previous colonoscopy.

This is a "substantial risk reduction," comment the study authors, headed by Hermann Brenner, MD, MPH, from the German Cancer Research Center in Heidelberg, Germany.

However, the risk reduction was seen only in left-sided advanced neoplasms and not right-sided ones, the researchers point out. A previous colonoscopy was associated with a 67% reduced risk for advanced neoplasia in the left side of the colon and the rectum, but no risk reduction was seen in the right side of the colon.

"However, because most neoplasms in the colon and rectum are located on the left side, substantial overall risk reduction for colorectal cancers and advanced adenomas was observed," they add.

"Remarkably Consistent" With Previous Studies

These results are "remarkably consistent with a number of recently published studies, all of which demonstrate the overall effectiveness of colonoscopy for reduction of colorectal cancer incidence and mortality but with a marked variance in effectiveness for proximal and distal cancers," comment editorialists Nancy Baxter, MD, PhD, from St. Michael's Hospital, Toronto, Ontario, Canada, and Linda Rabeneck, MD, MPH, from the Odette Cancer Center, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.

They add that the study is an important contribution to the observational evidence that "must inform our understanding of the effectiveness of colonoscopy."

The editorialists also point out that observational evidence is all that is available at present to address the question of how effective colonoscopy is at reducing the burden of colorectal cancer in the population. A definitive answer can come only from a randomized trial, and although one is underway (the Northern European Initiative on Colorectal Cancer), outcome data are not expected until 2026.

In the meantime, as the observational evidence continues to mount, the answer to this question becomes less certain, they suggest.

Is Right-Sided Colon Cancer Different?

One of the limitations of this study was the small number of advanced neoplasms found at any location, the researchers comment. "Nevertheless, consistent patterns of risk reduction in all parts of the left colon and rectum were observed, with absence of risk reduction in all parts of the right colon," they add. These site-specific findings are also "remarkably consistent" with several previous studies, they note.

"Possibly, the lack of effect in the right colon could be overcome to some extent by enhanced training of endoscopists, by enhanced measures of quality assurance, and by development of technology that enhances inspection of the right colon," they suggest.

"Nevertheless, the possibility that cancer in the right colon simply does not lend itself equally well to early detection on biological grounds has to be considered," they continue. "If this possibility could be demonstrated in other investigations, then the relative merits of sigmoidoscopy and colonoscopy in the early detection and prevention of colorectal cancer would need to be re-evaluated."

In their editorial, Drs. Baxter and Rabeneck add that there is "compelling evidence that colonoscopy is a less effective tool in the proximal colon than [the] distal colon," but they also add that the "underlying reasons for the differential performance are unclear."

"There may be biological differences that limit the potential effectiveness of colonoscopy in the proximal colon," the editorialists continue. "Right-sided colonic adenomas tend to be flatter than left-sided lesions and are, therefore, harder to identify and remove."

The potential limitations of colonoscopy for preventing colorectal cancer in the proximal part of the colon — as identified in this and other studies — raises very important questions, the editorialists note. Is there an incremental benefit of colonoscopy vs flexible sigmoidoscopy for colorectal cancer screening? Also, if there is an incremental benefit, is it large enough to justify the additional risks and cost of colonoscopy for screening in the population, they ask.

The study was supported in part by a grant from the Central Research Institute of Ambulatory Health Care in Germany. The study authors and editorialists have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online December 30, 2009.

BIOMARKERS FOR OVARIAN CANCER DETECTION NOT SUFFICIENTLY ACCURATE

December 30, 2009 — Ovarian cancer is often a lethal disease, and one reason for this dismal prognosis is that it is usually not diagnosed until it has reached an advanced stage. Early detection could help reduce the associated mortality rate, but currently there are no specific and sensitive screening methods. Potential ovarian cancer biomarkers include cancer antigen CA125, human epididymis protein 4 (HE4), mesothelin, B7-H4, decoy receptor 3 (DcR3), and spondin-2 proteins. Researchers now report that serum concentrations of CA125, HE4, and mesothelin may provide evidence of ovarian cancer 3 years before a clinical diagnosis is made.

However, these biomarkers only become substantially elevated in the last year before diagnosis, according to findings published in the January 6, 2010, issue of the Journal of the National Cancer Institute.

However, although these markers are not accurate enough to prompt early intervention in existing screening protocols, the study authors explain, modest but statistically significant increases in risk associated with CA125, HE4, and mesothelin were identified. This finding is consistent with many of the established epidemiologic risk factors for ovarian cancer.

"I still think biomarkers may play a role in a cost-effective screening program, although none of these seem accurate enough either alone or together to justify their use in average-risk women," lead author Garnet Anderson, PhD, told Medscape Oncology.

"I do not know of any other currently identified biomarkers that hold more promise than these, but there has been a massive effort over the last few years to identify candidates and not all have been thoroughly vetted," said Dr. Anderson, who is with the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, Washington.

One problem, cites Dr. Anderson, may lie in the approach used in identifying candidate biomarkers. "Most of the discovery work done so far has been conducted in women with advanced-stage disease and compared them to healthy women," she explained. "If discovery work were done in samples like the ones we used here, representing specimens collected months to years prior to the advanced stage diagnosis, we might have a better chance of finding earlier signals of aggressive disease."

Another opportunity for improving screening and early diagnosis lies in imaging, she adds. "Currently the most common and only affordable imaging option that could be considered for routine screening is transvaginal ultrasound, but it performs poorly in terms of accurately determining those women [who] have ovarian cancer from those who do not," said Dr. Anderson. "A substantial improvement in this area would be very exciting."

Detectable Levels Reached Shortly Before Diagnosis

In this study, Dr. Anderson and colleagues analyzed prediagnostic serum samples and patient data from the Carotene and Retinol Efficacy Trial, a randomized chemoprevention trial that evaluated the effects of beta-carotene and retinol on the incidence of lung cancer among individuals at high risk for the disease.

The serum samples were obtained 0 to 18 years before a diagnosis of ovarian cancer was made in 34 patients (15 with advanced-stage serous carcinoma) and during a comparable interval before the reference date from 70 matched control subjects. Immunoassays were conducted to determine concentrations of CA125, HE4, mesothelin, B7-H4, DcR3, and spondin-2 proteins in the samples.

Results showed that concentrations of CA125, HE4, and mesothelin became slightly elevated in patients with ovarian cancer vs the control subjects approximately 3 years before their diagnosis. However, these biomarkers only reached detectable elevations within the final year before diagnosis. Thus, the discriminatory power of the markers was limited, the study authors note, because accuracy only increased shortly before diagnosis.

Not the Last Word

In an accompanying editorial, Patricia Hartge, ScD, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, Bethesda, Maryland, notes that it has been "surprisingly difficult" to create a successful screening program for asymptomatic women with ovarian cancer.

However, the authors of this study have taken a "valuable step toward the successful design of such a screening program by demonstrating one reason why screening regimens that are based on markers, or panels of markers, can fail," writes Dr. Hartge.

She points out that these results are "not the last word in serum markers or in combinations of markers." Instead, serum markers are likely to form a key element in any screening regimen, with the lead time and other parameters being taken into account.

However, for right now, there are no proven biomarkers, panel of biomarkers, or overall screening program that works well, explained Dr. Hartge. "The current report, with its sobering implications, brings us closer to understanding the crucial elements in designing any effective early detection program for ovarian cancer."

The National Cancer Institute funded the study. Dr. Anderson has disclosed no relevant financial relationships. Coauthor Lieling Wu is currently employed by Baxter Healthcare, Inc, and holds stock in this company but is not involved in projects related to ovarian cancer.

J Natl Cancer Inst. 2010;102:1-3, 26-38.

FIGITUMUMAB FOR EWING SARCOMA

December 29, 2009 — An experimental agent has demonstrated antitumor activity in Ewing's sarcoma, according to results of a preliminary study published in the December 24 online issue of the Lancet Oncology.

Figitumumab, developed by Pfizer, was shown to be safe for both adult and pediatric patients with sarcoma and also showed single-agent antitumor activity in different subtypes of the disease.

Of 28 patients who were assessed for a response to figitumumab, 2 patients with Ewing's sarcoma experienced objective responses — 1 complete response and 1 partial response. In addition, 8 other patients had disease stabilization (6 with Ewing's sarcoma, 1 with synovial sarcoma, and 1 with fibrosarcoma) that lasted 4 months or longer.

Possible Benefit From Insulin-Like Growth-Factor-1 Receptor Inhibitors

Figitumumab is a fully human immunoglobulin G2 monoclonal antibody that targets the insulin-like growth-factor-1 receptor (IGF-1R). The IGF-1R signaling pathway is involved in sarcomagenesis and regulates cellular growth, proliferation, survival, and transformation, and plays a critical role in the growth of tumor cells, the study authors note. IGF-1R has also specifically been implicated in the growth, metastasis, and angiogenesis in Ewing's sarcoma, with early reports showing antitumor activity of IGF-1R-targeting drugs in these conditions.

However, although there is reason for optimism regarding use of IGF-1R inhibitors in patients with Ewing's sarcoma, it is also crucial to identify the subset of patients who are most likely to respond to this therapy, notes an accompanying editorial.

"Despite the strong preclinical evidence that suggests a universal benefit with inhibiting IGF-1R, the progressive disease seen in some patients indicates that not all tumors are addicted to IGF-1R signaling or develop rapid resistance," write Jeffrey A. Toretsky, MD, from Georgetown University, Washington, DC, and Richard Gorlick, MD, from the Albert Einstein College of Medicine of Yeshiva University, Bronx, New York.

Because many drug makers are currently developing IGF-1R inhibitors, there could be "ample opportunity to optimize clinical benefit from IGF-1R blockade, although the development of these antibodies may be complicated," they explain. "Five-drug chemotherapy is routine in the treatment of Ewing's sarcoma; therefore, improvement in outcome for these patients will likely require demonstration of the feasibility of combining the antibody with standard chemotherapy."

Well Tolerated and Responses Seen

The phase 1 study was conducted by Johann S. de Bono, MBBS, PhD, of the Institute for Cancer Research, Sutton, United Kingdom, and the Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, and colleagues. Between January 2006 and August 2008, a total of 29 patients with refractory, advanced sarcomas were separated into 2 groups within the same trial: the first cohort (n = 15) included patients 18 years or older with multiple subtypes of sarcoma, and the second group (n = 14) consisted of patients 9 years or older with refractory Ewing's sarcoma.

All patients received intravenous figitumumab 20 mg/kg and continued with their treatment until disease progression or unacceptable toxicity. The primary endpoint of the study was to assess the safety and tolerability of figitumumab, and secondary endpoints included pharmacokinetic profiling and preliminary antitumor activity.

For all patients in this study, the rate of nonprogression at 3 months was 34% (95% confidence interval [CI], 10% - 58%) and at 6 months was 28% (95% CI, 5% - 51%). The authors observed objective antitumor activity in patients with Ewing's sarcoma. One patient had a complete response that has lasted 21.5 months to date, whereas a second patient had a partial response that has lasted 11.4 months. Both are still continuing to receive treatment, the authors note. In addition, disease stabilization has lasted more than 9 months in 4 patients (range, 9.8 - 16.1 months), and 2 of these patients also are continuing to receive this treatment.

Apart from the 2 patients who had a response, 5 other patients with Ewing's sarcoma experienced shrinkage of the target tumor lesions, and the authors observed small reductions in tumor size among some patients with chondrosarcoma, fibrosarcoma, and synovial sarcoma.

Figitumumab was well tolerated in this population, and adverse events were primarily mild to moderate in severity and were reversible. Grade 3 events included deep venous thrombosis (n = 1), vomiting (n = 1), and back pain (n = 1). Grade 3/4 laboratory abnormalities were seen in 2 patients, and grade 1 hyperglycemia occurred in 4 patients. A delayed onset of puberty was noted in 1 prepubertal male patient who is still receiving treatment.

The researchers conclude that figitumumab is well tolerated and has antitumor activity in Ewing's sarcoma, thus warranting further investigation. "Phase 2 studies of figitumumab and other anti-IGF-R agents in Ewing's sarcoma and other sarcoma subtypes are now completing accrual and rational combinations with other treatments are also being pursued," they write.

Pfizer Global Research and Development funded the study. Several of the study authors have received research funding from, have served in a consultant or advisory role, are employees, own stock, or received honoraria for Pfizer Oncology, as detailed in the original article.

Lancet Oncol. Published online December 24, 2009.

PSA VELOCITY AND PROSTATE CANCER RISK

NEW YORK (Reuters Health) Dec 21 - Prostate-specific antigen velocity (PSAV), increasingly recognized as a marker of potentially lethal prostate cancer, can also predict the likelihood that a given patient's cancer is insignificant, researchers say.

"A controversy of current prostate specific antigen based prostate cancer screening is the over detection of potentially insignificant prostate cancer," Dr. William J. Catalona, of Northwestern Feinberg School of Medicine, Chicago, and colleagues write. "A promising marker is prostate specific antigen velocity (rapidly increasing PSA)."

The 2010 National Comprehensive Cancer Network Guidelines recommend a PSAV threshold of about 0.35 to 0.4 ng/mL per year for prostate cancer screening protocols. Dr. Catalona and his co-authors sought to determine "whether this PSAV threshold is associated with...histologically insignificant prostate cancer at radical prostatectomy."

As they report in the January issue of the Journal of Urology, their study focused on 1073 men who underwent radical prostatectomy between 1992 and 2008. Insignificant prostate cancer was defined (on the basis of the Ohori criteria) as confined to the prostate, with a tumor volume 0.5 cc or less and no Gleason pattern 4 or 5.

The patients' mean age was 62 years. Their median PSA at diagnosis was 4.3 ng/mL, and most had a clinical stage T1c disease with a Gleason score of 6.

Preoperative PSAV greater than 0.4 ng/mL per year was significantly associated with positive surgical margins (19% versus 12%, p = 0.003) seminal vesicle invasion (4% versus 1%, p = 0.007), a Gleason score of 7 or greater (p = 0.008), and greater tumor volume.

Sixty-nine men (6%) had pathologically insignificant cancer. Insignificant disease was significantly more likely in men with preoperative PSAV less than 0.4 ng/mL per year (10%, vs. 5% for PSAV greater than 0.4 ng/mL per year; p = 0.003).

"These results suggest that PSAV may be useful in conjunction with other variables to help enhance the specificity of prostate cancer screening to detect clinically significant prostate cancer," the authors conclude.

J Urol 2010;183:112-117.

NEW STANDARD IN EARLY STAGE HODGKIN LYMPHOMA

December 21, 2009 (New Orleans, Louisiana) — A new standard of care for the treatment of early-stage Hodgkin's lymphoma has now been established. The final results from a large German study presented here at the American Society of Hematology 51st Annual Meeting show that the best results were seen with a combination of chemotherapy and radiation.

Two cycles of chemotherapy with ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, dacarbazine) followed by 20 Gy involved-field radiotherapy (IFR) is the new standard of care for patients with Hodgkin's lymphoma in early favorable stages, concluded lead researcher Andreas Engert, MD, from the University of Cologne, Germany.

In the discussion period following his presentation, several experts congratulated him and agreed that this should be the new standard of care. In an interview with Medscape Oncology, Richard Van Etten MD, PhD, director of the Cancer Center at Tufts Medical Center, in Boston, Massachusetts, explained that there was a long-standing question about the treatment of these patients with favorable early-stage disease, and this trial has finally offered an answer as to what is the best option.

Ongoing Debate About Best Approach

In the ongoing debate about the best approach to the treatment of patients with early favorable Hodgkin's lymphoma, one of the main questions has been whether to use chemotherapy alone or chemotherapy in combination with radiation, but there have also been questions about the optimum radiation dose and about the optimal number of chemotherapy cycles, Dr. Engert explained.

The German Hodgkin Study Group addressed these questions in a large trial, conducted in 1370 patients, which had 4 treatment groups. Each group had a different combination of chemotherapy with ABVD (2 or 4 cycles) and IFR (20 Gy or 30 Gy).

The 4 treatment groups were: 4 cycles of ABVD plus 30 Gy IFR; 4 cycles of ABVD plus 20 Gy IFR; 2 cycles of ABVD plus 30 Gy IFR; and 2 cycles of ABVD plus 20 Gy IFR.

All of the groups showed a similar efficacy, but there were significant differences in toxicity, Dr. Engert told the meeting.

Complete remission was achieved in 97% of patients who were treated with either 4 or 2 cycles of ABVD and who received 20 Gy IFR, and in 99% of patients who received 30 Gy.

With a median follow-up of 79 to 91 months, there was no significant difference between 4 and 2 cycles of chemotherapy in terms of overall survival at 5 years (97.1% with 4 cycles of ABVD and 96.6% with 2 cycles), in freedom from treatment failure (93% vs 91.1%), or in progression-free survival (3.5% vs 91.2%).

There were also no significant differences between the 2 doses of radiotherapy in terms of overall survival at 5 years (97.6% with 30 Gy and 97.5% with 20 Gy), in freedom from treatment failure (93.4% vs 92.9%), or progression-free survival (93.7% vs 93.2%).

"Importantly, there were also no significant differences in overall survival, freedom from treatment failure, or progression-free survival when all 4 arms were compared," Dr. Engert explained.

However, there were significant differences in toxicity, Dr. Engert reported. Four cycles of ABVD were significantly more toxic than 2 cycles. Overall adverse events were reported in 52% of patients receiving 4 cycles and in 33% receiving 2 cycles; leukopenia was seen in 24% and 15%, respectively, and alopecia was seen in 28% and 15%, respectively.

A similar pattern was seen with radiotherapy, with more toxicity at the higher dose. Overall adverse events were reported in 8.2% of patients treated with 30 Gy and in 2.9% treated with 20 Gy, dysphagia was seen in 3% and 2%, respectively, and mucositis was seen in 3.4% and 0.7%, respectively.

Dr. Engert concluded that because all of the treatment groups showed a similar efficacy, the new standard of care should be the least toxic treatment of 2 cycles of ABVD and 20 Gy IFR.

Dr. Engert also said that his group is continuing with this research and is looking at whether the radiotherapy portion of the treatment is necessary. A new trial will compare 2 cycles of ABVD with and without the addition of 20 Gy IFR. In addition, an ongoing study is looking at the various components of the chemotherapy regimen to see if any drug can be dropped, he said. This trial is comparing ABVD with ABV, AVD, and AV, he added.

The researchers have disclosed no relevant financial relationships.

American Society of Hematology (ASH) 51st Annual Meeting: Abstract 716. Presented December 7, 2009.