		Clinical Psychology Postdoctoral Fellow

		Integrative Oncology and Behavioral Sleep Medicine Abramson Cancer Center

Cognitive behavioral therapy for insomnia (CBT-I) and mindfulness-based stress reduction (MBSR) can improve sleep for patients with cancer, but CBT-I continues to be the best nonpharmacologic option, according to findings of a study directly comparing the two approaches.

It is estimated that between 36% and 59% of patients with cancer suffer from sleep disorders during and following cancer treatment, and up to 28% of patients with cancer receive a formal diagnosis of insomnia. Although medications are available for the treatment of insomnia, many patients do not want to add to the already long list of medications they must take and also worry over possible side effects, drug interactions, and developing dependence.

For the study, 111 adults who received treatment at a Canadian tertiary cancer center for nonmetastatic cancer were randomly assigned to receive either CBT-I (n = 47) or MBSR (n = 64). The CBT-I protocol involved stimulus control, sleep restriction, cognitive therapy, and relaxation training. The MBSR program offered a psychoeducational component explaining the link between stress and health, accompanied by the practice of meditation techniques and gentle yoga. Both cohorts received 90-minute interventions weekly for 8 weeks. The MBSR group also participated in a 6-hour weekend retreat. To be eligible for the trial, participants needed to have completed their chemotherapy and radiotherapy treatments at least 1 month prior to enrollment; those taking psychotropic drugs could participate if their dosage had not changed over the previous 6 weeks.

The study’s primary outcome, insomnia severity, was measured by the Insomnia Severity Index (ISI), a seven-item questionnaire which assesses difficulties with sleep onset and sleep maintenance, the extent to which sleep problems interfere with daily function, and distress levels elicited by insomnia.

The researchers determined that a reduction of at least eight points on the ISI would be needed to demonstrate a reduction in insomnia severity, and they set a four-point noninferiority margin for comparing the two interventions.

Secondary outcomes of the study included sleep quality, sleep beliefs, mood, and stress. Patient sleep diaries and actigraphy monitoring were used to determine sleep efficiency, sleep onset latency, wake after sleep onset, and total sleep time.

Patients were assessed at baseline, at the end of the program, and at 5 months. After completing the 8-week programs, both CBT-I and MBSR resulted in reduced insomnia severity; the CBT-I cohort experienced more rapid results, whereas MBSR led to a more gradual improvement. At the 5-month follow-up, MBSR met the established noninferiority criterion.

Sleep onset latency was reduced by 22 minutes in the CBT-I cohort and by 14 minutes for those receiving the MSBR. Total sleep time increased by 0.60 hours with CBT-I and 0.75 hours with MBSR. Both groups experienced a reduction in the time it took to fall asleep and return to sleep during the night, as well as improvements in mood and stress-related symptoms.

“Insomnia and disturbed sleep are significant problems that can affect approximately half of all cancer patients,” said lead study author Sheila N. Garland, PhD, a clinical psychology postdoctoral fellow in Integrative Oncology and Behavioral Sleep Medicine at Penn’s Abramson Cancer Center, in a press release announcing the study findings.

“If not properly addressed, sleep disturbances can negatively influence therapeutic and supportive care measures for these patients, so it’s critical that clinicians can offer patients reliable, effective, and tailored interventions.”

Garland added that the study’s findings expand available treatment options for insomnia in cancer patients.

“This study suggests that we should not apply a ‘one-size-fits-all’ model to the treatment of insomnia and emphasizes the need to individualize treatment based on patient characteristics and preferences.”

Significant attrition occurred in the MBSR group, which, the researchers suggested, may be a result of patient preference and poses a possible limitation of the study, along with the fact that 27 potential participants were excluded because they had already engaged in an MBSR program. The researchers posited that when compared with the CBT-I intervention, the benefits of the MBSR approach may be less evident to those not already inclined toward a meditation/yoga approach.

1. Garland SN, Carlson LE, Stephens AJ, et al. Mindfulness- based stress reduction compared with cognitive behavioral therapy for the treatment of insomnia comorbid with cancer: a randomized, partially blinded, noninferiority trial [published online January 6, 2014]. 

Articles

Cognitive behavioral therapy for insomnia (CBT-I) and mindfulness-based stress reduction (MBSR) can improve sleep for patients with cancer, but CBT-I continues to be the best nonpharmacologic option

Patients Coping With Insomnia May Benefit from Behavioral Interventions

Treatment with the oral PI3K-delta inhibitor idelalisib produced an overall response rate (ORR) of 57% with an average response duration of 12.5 months in heavily pretreated patients with indolent non-Hodgkin’s lymphoma (iNHL), according to pivotal phase II data.

The results were presented in December at the 55th Annual Meeting of the American Society of Hematology (ASH) and were recently published in 

 The FDA has accepted a New Drug Application for idelalisib in refractory iNHL based on these data, with an approval decision expected on or before September 11, 2014.

Indolent non-Hodgkin’s lymphoma is currently treated with a combination of rituximab (Rituxan) and chemotherapy. This treatment is not curative and has shown decreasing efficacy with each administration.

The single-agent, phase II Study 101-09 involved 125 patients with various types of iNHL, including follicular lymphoma (72 patients), small lymphocytic lymphoma (28), marginal-zone lymphoma (15), and lymphoplasmacytic lymphoma with or without Waldenström’s macroglobulinemia (10). The majority of patients (89%) had stage III or IV disease and all patients had not responded favorably to rituximab and an alkylating agent or had relapsed within 6 months of treatment.

The median patient age was 64 years and the median number of therapies patients previously received was 4 (range, 2-12). Thirty percent of patients had elevated lactate dehydrogenase levels, 26% had lesions that were ≥7 cm in at least one dimension, 15% had a hemoglobin level <10 g/dL, and 14% had a neutrophil count <1500/mm3. Lead author Ajay Gopal, MD, director of Clinical Research for Hematology at the Seattle Cancer Care Alliance, and colleagues treated patients with 150 mg of idelalisib twice daily until disease progression or withdrawal from the study. ORR was the primary endpoint. Duration of response, progression-free survival (PFS), and safety were secondary endpoints.

The 57% ORR was determined by a ≥50% reduction in tumor size in 71 of 125 patients. Complete response (no measurable evidence of cancer) was reached in 6% of patients.

The median time to response was 1.9 months. Median PFS was 11 months. At the time of the analysis, the median overall survival (OS) was 20.3 months, with an estimated 1-year OS of 80%. The most commonly reported grade ≥3 adverse events were diarrhea (13% of patients), pneumonia (7%), and dyspnea (3%). Neutropenia (27%) and elevations in levels of serum alanine or aspartate aminotransferase (13%) were the most frequent grade ≥3 laboratory abnormalities that occurred during treatment. Additionally, the rates of grade ≥3 thrombocytopenia and anemia were 6% and 2%, respectively.

During the study, 28 deaths (22%) were reported. Of those, 11 deaths occurred during study treatment or within 30 days of the last dose. Causes of death included progressive disease (3 patients), pneumonia (3), and one case each of cardiac arrest, cardiac failure, splenic infarction, septic shock, and pneumonitis. The remaining 17 deaths occurred during long-term followup and were predominantly due to progressive disease. There was no evidence of cumulative toxic effects documented.

Gilead Sciences, Inc, which manufactures idelalisib, has also submitted a New Drug Application for the drug to treat patients with relapsed chronic lymphocytic leukemia (CLL). Idelalisib has received the FDA’s Breakthrough Therapy designation for this indication.

The CLL submission was based on the phase III Study 116, which found that the combination of idelalisib and rituximab significantly improved OS, PFS, and response rate in patients with high-risk relapsed/refractory CLL. The results of the study were also presented at the 55th ASH Annual Meeting and published in 

			Gopal AK, Kahl BS, de Vos S, et al. PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma [published online January 22, 2014]. 

			Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia [published online January 22, 2014]. 

Treatment with the oral PI3K-delta inhibitor idelalisib produced an overall response rate of 57% with an average response duration of 12.5 months in heavily pretreated patients with indolent non-Hodgkin's lymphoma.

Idelalisib Shows Promising Activity in Heavily Pretreated iNHL

Intensity-modulated radiation therapy (IMRT) improved survival and reduced toxicities compared with conventional radiation treatment in patients with head and neck cancer, according to a recent database analysis. The review was conducted by researchers at The University of Texas MD Anderson Cancer Center and was recently published in the journal Cancer.

IMRT was approved in 1999 to treat head and neck cancers and is designed to precisely target cancer cells while sparing nearby tissue. Although it is more expensive than conventional radiation, it has been widely adopted because it lowers toxicities such as xerostomia, dental complications, fibrosis, and motion impairments.

“Previous studies indicated that patients treated with IMRT did better when it came to treatment-related side effects, however these studies were not designed to examine survival,” said lead author Beth Beadle, MD, PhD, assistant professor in MD Anderson’s Department of Radiation Oncology, in a press release. “The survival data was not well-known because IMRT is intended to spare normal tissues but still deliver radiation to the tumor so previous models assumed it was equivalent survival at best.”

The researchers identified 3172 patients in the SEERMedicare database who had been treated for head and neck cancer between 1999 and 2007. Of the overall population, 1056 patients (33.3%) had received IMRT and 2116 (66.7%) were treated with conventional radiation. Overall, 1018 patients (32.1%) had surgery and adjuvant radiation therapy, and 2154 patients (67.9%) had definitive radiation therapy.

The most common type of head and neck cancer, squamous cell carcinoma, accounted for 91.2% of the study population. The primary cancer site among patients was oral cavity and oropharynx (58.3%), followed by larynx (18%) and hypopharynx (10.7%). The mean age at diagnosis was 72.2 years (range, 66-80). Primary outcome was identified as cause-specific survival (CSS), reflecting the chances of dying from head and neck cancer after 40 months of follow-up.

The study found that patients who were treated with IMRT had significantly improved CSS rates compared with patients who received conventional therapy: 84.1% versus 66% (

“From a scientific perspective, the findings support the use of IMRT and suggests we can provide excellent care while optimizing cancer outcomes and reducing toxicities,” said Beadle. “At a more global level, with concerns about healthcare financing and resource allocation, IMRT is more expensive than conventional radiation therapy, but the data suggest it’s worth it.”

In their analysis, Beadle et al referenced a separate study by Yong et al that examined the cost-effectiveness of using IMRT to treat oropharynx cancer. The study by Yong et al concluded that the IMRT technology could prove to be more cost-effective and therapeutically effective by reducing the need for costly salvage therapy for tumor recurrences and for side-effect management expenses, even if the upfront radiotherapy costs are higher.

Beadle said that additional work is needed to further examine the cost-effectiveness of IMRT, but if the therapy can reduce or eliminate subsequent disease recurrences or treatment-related side effects, the impact on cost would be favorable.

			Beadle BM, Liao KP, Elting LS, et al. Improved survival using intensity-modulated radiation therapy in head and neck cancers: a SEER-Medicare analysis [published online January 13, 2014]. 

			Yong JH, Beca J, O’Sullivan B, et al. Cost-effectiveness of intensity-modulated radiotherapy in oropharyngeal cancer. 

Intensity-modulated radiation therapy (IMRT) improved survival and reduced toxicities compared with conventional radiation treatment in patients with head and neck cancer, according to a recent database analysis.

Study Suggests IMRT Improves Survival in Head and Neck Cancer

		Chair, Department of Neurological Surgery

A personalized vaccine being tested as a therapy for recurrent glioblastoma multiforme (GBM) improved patient survival compared with standard treatments, according results of a study published in 

 that will help move the agent forward in clinical development.

The therapy tested in the multicenter, singlearm phase II trial was heat-shock protein peptide complex-96 (HSPPC-96), an autologous treatment made from dendritic cells extracted from patient’s tumor tissue after surgical resection with the aim of killing any tumor cells left behind. The vaccine contains a precise antigenic fingerprint of the patient’s cancer, and only targets cells with this fingerprint, greatly reducing the risk of off-target effects.

HSPPC-96 is part of the Prophage Series G-200 vaccine candidates, which have been funded in various studies by the National Cancer Institute and brain research advocacy organizations, according to Agenus Inc, the pharmaceutical developer. The Feinberg School of Medicine at Northwestern University is leading the research effort.

The vaccine’s results compare favorably with historical outcomes of patients with GBM, whose median survival is 15 months from time of diagnosis and 3 to 6 months after recurrence, Bloch et al reported.

 Chemotherapy and radiation following surgery are standard treatments for newly diagnosed GBM, but after recurrence, which is typical in the disease, there are no very effective therapies, said Andrew T. Parsa, MD, PhD, a coauthor of the study and chair of Neurological Surgery at Northwestern Memorial Hospital. The study followed patients who received the vaccine after surgery and standard adjuvant therapy.

		Figure. Key Statistics for 41 Patients in HSPPC-96 Vaccine Trial

With HSPPC-96, “Survival increased from an average of 33 weeks following progression to about 40 weeks,” said the study’s lead author, Orin Bloch, MD, a neurosurgeon at the hospital, in a press release. He described that result as “a substantial, though not enormous, increase in survival that gives us hope that vaccine therapy, perhaps in combination with other therapies, will increase survival and improve overall care.” In the study, overall survival at 6 months after treatment with HSPPC-96—the primary endpoint&mdash;was approximately 90%. After 12 months, nearly 30% of the patients were alive. Additional endpoints included overall survival, progression-free survival (PFS), safety, and immune profiling.

In all, 68 patients with recurrent GBM were screened and underwent surgical resection for the study from October 2007 through October 2011, researchers reported. Nearly 40% of the initial group (27 patients) were excluded postoperatively, including 13 patients from whom the tumor harvested was insufficient to generate the vaccine.

The resulting trial included an intent-to-treat population of 41 patients with a median age of 55 years (21-75 years) who had surgically resectable, recurrent, high-grade GBM. Karnofsky performance scores were >90 for 15 patients (37%), >80 for 20 patients (49%), and >70 for 6 patients (14%). Participants underwent surgery to remove more than 90% of the brain tumor (a gross total resection). The vaccine was then created for each patient using their removed mass, with approximately 7 g of tissue needed to produce a minimum of four 25-mg vaccine doses. The HSPPC-96 vaccine was administered once a week for 4 weeks, then every other week, with a median of 6 doses (range, 1-15 doses). Reasons for discontinuing the vaccine included disease progression (21 patients) and depleted vaccine (13 patients).

After treatment, 90.2% of patients were alive at 6 months (95% CI, 75.9-96.8) and 29.3% were alive at 12 months (95% CI, 16.6-45.7), the authors reported. Median overall survival was 42.6 weeks (95% CI, 34.7-50.5), they wrote. Patients who received a greater number of doses experienced statistically significant better outcomes, with a hazard ratio of 0.85 (95% CI, 0.73-0.99; 

 = .036) per incremental dosage. There were no treatment-related deaths.

During the trial, there were 37 serious (grade 3—5) adverse events reported. Seventeen could be attributed to the surgical resection, and 1 grade 3 constitutional event was related to the vaccine, the authors reported.

While HSPPC-96 had previously been tested in other tumor types, cancer vaccines work best in patients who have low residual disease, such as brain cancer, Parsa told OncologyLive. He said the HSPPC-96 vaccine was chosen for study because it flows well with treatment for patients who have GBM, with an interval of about two weeks between the tumor’s removal and the vaccine’s administration.

Parsa said that the main goals of the study were to prove the efficacy of the vaccine and prepare for a randomized three-arm trial (NCT01814813), currently under way, that will include about 200 patients. That trial is testing the efficacy of bevacizumab— considered a standard treatment for recurrent GBM&mdash;versus the cancer vaccine in tandem with bevacizumab, and is sponsored by the Alliance for Clinical Trials in Oncology, a cooperative group of the NCI.

In addition, an HSPPC-96 vaccine from the Prophage G-100 series that Agenus developed is under study for patients with newly diagnosed GBM in a combination regimen with temozolomide following radiation therapy (NCT00905060).

Forty-six patients have been treated in the phase II study, with a median PFS of 17.8 months, Agenus reported in September. The company is discussing a phase III trial with the FDA.

			Bloch O, Crane CA, Fuks Y, et al. Heat-shock protein peptide complex-96 vaccination for recurrent glioblastoma: a phase II, single-arm trial [published online December 12, 2013]. 

A personalized vaccine being tested as a therapy for recurrent glioblastoma multiforme (GBM) improved patient survival compared with standard treatments

Dendritic Vaccine Improves Survival in Recurrent Glioblastoma

 that are known to drive subsets of lung cancer are also present in colorectal cancer according to a recent study in 

. It is now hoped that the drugs targeting ALK and ROS1 can also be applied to treat patients with colorectal cancer (CRC).

Dara Aisner, MD, PhD, an investigator at the Colorado University (CU) Cancer Center and a molecular pathologist at the CU School of Medicine, and colleagues used fluorescence in situ hybridization (FISH) to test for the oncogenic gene arrangements in 236 tumor samples. Samples were collected from patients who had previously been studied as part of a clinical trial in Australia that looked at a particular chemotherapy combination in metastatic colon cancer and had histologically confirmed colorectal adenocarcinoma. From each patient, three tumor tissue cores were taken and distributed in 10 blocks, making up a 12x8 grid of cores on each slide. Thirtynine of the patients were sampled twice, and three were sampled three times for quality control.

Two cases (0.8%) showed FISH patterns that were consistent with 

 signals. One case (0.4%) exhibited a pattern consistent with 

 rearrangement and also had predominantly single 3’

 signals. Seven cases (3%) showed the atypical pattern 3’ALK doublets (3’/5’/3’

 were also identified, including 25 cases with 3’/5’ fusion ALK doublets (10.6%), and 12 cases each (5.1%) with 3’ROS1 doublets (3’/5’/3’

According to the study report, the researchers were surprised to find marked intratumoral heterogeneity for both 

 rearrangement status. Finding all four combinations of 

 status throughout the specimen was especially unexpected, as was the identification of a region of high-grade dysplasia harboring both molecular alterations. Several other studies have shown that the 

 mutation is an early event in colorectal carcinoma tumorigenesis.

“This is one of man y evolving studies demonstrating that while well described molecular alterations might be more common in a par ticular tumor type, to assume that they are exclusive to a single tumor type underestimates the diversity of biology,” Aisner explained in an interview with 

. “It is r eally only through sampling relatively large numbers of cases that we can f ind rare events, and in my mind, this further suggests that largescale evaluation for genomic alterations is an important part of the future of both scientific study and medicine. For colorectal carcinoma specifically, this identifies a rare but potentially targetable alteration that could provide treatment benefit for patients.”

Aisner said the researchers’ ultimate goal with this study is “to identify new targets for therapy for CRC patients, as well as patients with other tumor types.”

Aisner DL, Nguyen TT, Paskulin DD, et al. ROS1 and ALK fusions in colorectal cancer, with evidence of intratumoral heterogeneity for molecular drivers [published online ahead of print December 2, 2013]. 

Gene rearrangements ALK and ROS1 that are known to drive subsets of lung cancer are also present in colorectal cancer according to a recent study in Molecular Cancer Research.

ALK and ROS1 Lung Cancer Oncogenes May Also Drive Colorectal Cancer

Brentuximab vedotin (Adcetris) should not be given with bleomycin as a first-line therapy for patients with advanced-stage Hodgkin lymphoma, according to a phase I study comparing the agent in combination with standard (ABVD) or modified standard (AVD) treatment. The study also found that brentuximab vedotin combined with AVD is well tolerated by patients. An ongoing phase III trial (NCT01712490) will now determine whether frontline brentuximab vedotin plus AVD is better than ABVD for patients with Hodgkin lymphoma.

Standard treatment for Hodgkin lymphoma is approximately 4-6 cycles of ABVD—a combination of the chemotherapy drugs doxorubicin, bleomycin, vinblastine, and dacarbazine&mdash;and radiation therapy. This cycle of chemotherapy and radiation therapy can cause longterm side effects that include heart problems and other types of cancer.

Patients with relapsed Hodgkin lymphoma have successfully been treated with brentuximab vedotin, an antibody-drug conjugate containing an anti-CD30 monoclonal antibody. In this phase I, single-arm, openlabel, dose-escalation trial, Anas Younes, MD, chief of the Lymphoma Service at Memorial Sloan-Kettering Cancer Center, and colleagues sought to test whether combining brentuximab vedotin with ABVD or AVD would reduce the number of chemotherapy cycles needed to be effective as a treatment for newly diagnosed Hodgkin lymphoma.

Patient criteria for this study included treatment naïve, CD30-positive, aged 18 to 60 years, histologically confirmed stage IIA bulky or stage IIB—IV disease, ECOG performance status ≤2, and no known pulmonary disease requiring medication.

In the study, 51 patients were given intravenous infusions of brentuximab vedotin at 0.6, 0.9, or 1.2 mg/kg every 2 weeks with either ABVD (25 mg/m

 dacarbazine; n = 25) or AVD (same dosages without bleomycin; n = 26) for up to six cycles.

		Phase I Data for Brentuximab Vedotin Plus ABVD or AVD in Hodgkins Lymphoma

		Brentuximab vedotin is an antibody-drug conjugate containing an anti-CD30 monoclonal antibody.

Data are from 51 patients with newly diagnosed, treatment-naïve Hodgkins lymphoma who received brentuximab vedotin plus ABVD or AVD.

		ABVD indicates doxorubicin, bleomycin, vinblastine, and dacarbazine

The maximum tolerated dose of brentuximab vedotin combined with ABVD or AVD did not exceed 1.2 mg/ kg. Of 22 patients given brentuximab vedotin and ABVD who completed the study, 21 (95%) achieved complete remission. Of 25 patients given brentuximab vedotin and AVD who completed the study, 24 (96%) achieved complete remission. In the ABVD group, an unacceptable amount of pulmonary toxic effects (11 out of 25, 44%) were noted. No toxic pulmonary effects were noted in the AVD group.

The most common grade ≥3 adverse events included neutropenia (80% [20/25] of the ABVD group vs 77% [20 /26] of the AVD group), anemia (20% vs 12%), febrile neutropenia (20% vs 8%), pulmonary toxic effects (24% vs 0), syncope (12% vs 8%), dyspnoea (12% vs 4%), pulmonary embolism (12% vs 0), fatigue (4% each), and leucopenia (4% each).

Overall, serious events occurred in 56% of the ABVD group and 27% of the AVD group. Serious events occurring in >10% of patients included febrile neutropenia (16% in ABVD, 8% in AVD) and pulmonary toxicities (24%, ABVD group only).

Younes A, Connors JM, Park SI, et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin’s lymphoma: a phase 1, open-label, dose-escalation study. Lancet Oncol. 2013;14(13):1348-1356.

Brentuximab vedotin (Adcetris) should not be given with bleomycin as a first-line therapy for patients with advanced-stage Hodgkin lymphoma

Brentuximab Vedotin Should Not Be Combined With Bleomycin in First-Line Treatment of Hodgkin Lymphoma

A novel imaging technology was able to determine four days after treatment that experimental therapies for sarcoma were fighting the cancer in xenograft models, a study has demonstrated.

, Foroutan et al, of the H. Lee Moffitt Cancer Center & Research Institute in Tampa, Florida, used diffusion-weighted magnetic resonance imaging (MRI) to evaluate the activity of gemcitabine and Wee-1 cell cycle checkpoint inhibitor MK1775 in an osteosarcoma xenotransplant model soon after treatment.

Previous studies had found that standard techniques for volumetric analysis, including more conventional forms of MRI, could not accurately assess changes to tumor biology in sarcoma. The newer technology measures water mobility in biological tissue, quantified as Apparent Diffusion Coefficients (ADC); a rising ADC just after treatment may signify cancer cell death, the authors wrote. This application of the technology has not previously been investigated or reported, they added.

The authors embarked on the investigation because novel therapies to replace surgical resection followed by chemotherapy are critically needed in sarcoma, where progress has been hampered by the disease’s heterogeneity, and cure rates have not improved much in the last decade. In previous studies, gemcitabine and MK1775 demonstrated an ability to kill cancer cells, but a better way to measure their activity, particularly soon after treatment, was needed, the authors wrote.

For the study, tissue was harvested during an initial core biopsy of a distal femur osteosarcoma that was metastatic to the lungs. The osteosarcoma patient was chemotherapy-naïve at the time of biopsy. The harvested tissue was subcutaneously transplanted into both flanks of 16 six-week old female SHO/SCID athymic mice. When the tumors reached 500 mm

, the mice were randomly assigned to four treatment groups: a control group; a group receiving oral MK1775; a cohort receiving gemcitabine by intraperitoneal injection; and a group taking both MK1775 and gemcitabine. Each mouse had two implanted tumors, so there were 8 tumors per treatment group.

The investigators examined multiple descriptors of ADC parameters in the mice at baseline, 24 hours after each drug administration, and at day 14. They observed reduced cellularity and larger ranges in cell sizes for treated groups by day 4 of treatment.

Specifically, the researchers found that gemcitabine, with or without MK1775, significantly slowed tumor growth by day 4 after treatment; this response was heralded 24 hours after treatment by significant elevations in mean tumor ADC, ADC distribution, and entropy. Gemcitabine sparked apoptosis, and the increased ADC values that investigators observed correlated with that activity.

Further, the authors found, when tumor control happened slowly with MK1775 monotherapy, there were no significant changes in ADC or ADC distribution, indicating that therapy-induced edema can be absorbed faster than it is created. Since the MRI technology tested in the study was only able to measure apoptosis that occurred very rapidly, it could be useful in the assessment of the most active new agents, the authors suggested.

A novel imaging technology was able to determine four days after treatment that experimental therapies for sarcoma were fighting the cancer in xenograft models

Novel Imaging Identifies Changes in Osteosarcoma Earlier in Treatment

A new study has shown a possible correlation between men with short-ended chromosomes in the immune cells of their blood and an increased risk of developing aggressive prostate cancer, potentially pointing the way toward an accessible biomarker that could help inform treatment and surveillance decisions. An association between smoking and more aggressive disease also was uncovered.

Researchers from Johns Hopkins Medicine in Baltimore presented these findings from a retrospective study at the 12th Annual AACR International Conference on Frontiers in Cancer Prevention Research, held in October in National Harbor, Maryland.

The analysis built upon the team’s earlier research that examined whether alterations in telomere length in surgically treated men with primary prostate cancer could predict whether an individual patient would progress to metastasis and death from the disease (

“We found that men with prostate cancer who had high variability in the length of telomeres from one prostate cancer cell to another and shorter telomere length in prostate cancer-associated stromal cells were substantially more likely to develop metastases or die of their disease compared with men with prostate cancer harboring neither of these characteristics,” Elizabeth A. Platz, ScD, MPH, a professor in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health who presented the most recent findings at the AACR meeting, said in a statement.

In the new study, the goal was to determine whether circulating leukocyte telomere length more accessibly found in the blood could serve as a surrogate for prostate cell telomere length.

The study drew from the 18,018 members of Harvard University’s Health Professionals Follow-up Study, including 441 men who had developed prostate cancer and 421 men who did not develop prostate cancer. The men had provided blood samples in 1993—1995 and were followed through January 2000. The average time of cancer diagnosis was three years from first blood draw.

Using quantitative PCR, investigators measured relative telomere length in leukocytes from the blood samples and categorized these values based on distribution in the control group.

Among men who developed prostate cancer, those with telomeres in the bottom two tertiles for length—the shortest telomeres&mdash; were more than twice as likely to develop an aggressive form of prostate cancer (odds ratio [OR] = 2.29, 95% CI 0.99-5.34) when compared with those who had telomeres in the top tertile for length. When the researchers further refined the results into smokers and non-smokers, they found that those who were ever-smokers were more than four times as likely to have developed aggressive prostate cancer (OR = 4.47, 95% CI 0.99-20.2).

Platz EA, Heaphy CM, De Vivo I, et al. Prospective association between circulating leukocyte telomere length and risk of aggressive prostate cancer. Presented at 12th Annual AACR International Conference on Frontiers in Cancer Prevention Research; October 27—30, 2013; National Harbor, MD. Abstract C20.

A new study has shown a possible correlation between men with short-ended chromosomes in the immune cells of their blood and an increased risk of developing aggressive prostate cancer, potentially pointing the way toward an accessible biomarker that could help inform treatment and surveillance decisions. 

Haydia Haniff