Tuesday, April 21, 2015
Approximately half of cancer patients scheduled for major surgery are anemic. Also, a significant number of patients will present to the operating room with low platelet counts and coagulopathic disorders. Unfortunately, administration of red blood cells, platelets concentrates and fresh-frozen plasma is associated with unwanted adverse effects including fever, hemolytic reactions and transfusion-related immunomodulation (TRIM). TRIM is a multifactorial immunologic phenomenon in the recipient mediated by donor leukocytes, microparticles such as ectosomes, and growth factors. As some of these molecules are secreted in a time-dependent manner, blood storage time may play an important in TRIM, although the evidence is limited. Perioperative administration of red blood cells and associated TRIM has also been associated with increased recurrence of certain solid tumors, such as colorectal, lung, and hepatobiliary tumors. In this continuing education article, we review the available evidence on how perioperative blood product transfusions can affect oncological outcomes, such as cancer recurrence.
A Phase 2 study of cediranib in recurrent or persistent ovarian, peritoneal or fallopian tube cancer
A Trial of the Princess Margaret, Chicago and California Phase II Consortia
- •Cediranib has activity in recurrent ovarian cancer
- •Expected toxicities were manageable with a dose reduction of cediranib (30 mg daily)
Cediranib is a potent multitargeted inhibitor of vascular endothelial growth factor receptor (VEGFR) 1, 2 and 3. The study was initiated to evaluate the activity of cediranib in patients (pts) with recurrent ovarian, peritoneal or fallopian tube cancer (OC).
MethodsEligible pts had persistent/recurrent OC following one prior platinum-based chemotherapy with measurable disease or progression based on Gynecologic Cancer Inter Group CA-125 criteria. Because of toxicities observed in the first 23 pts, the initial starting dose of oral daily (od) cediranib was reduced from 45 mg to 30 mg. The primary endpoint was objective response rate at 16 weeks. This study was stratified into two arms: platinum-sensitive (PL-S) and platinum-resistant (PL-R).
Results74 pts were enrolled; 39 were PL-S and 35 PL-R, with a median age of 58 years [31–87]. In PL-S group, 10 partial responses (PR) and stable disease (SD) in 20 (51%) were confirmed while in the PL-R arm there were no confirmed PR and 23 pts (66%) had SD. The main grade 3/4 toxicities were hypertension (24%), fatigue (17%) and diarrhea (9%). The median progression-free survival for all patients was 4.9 months [3.9-7.0], 7.2 months [4.3-9] for PL-S and 3.7 months [2.6-4.5] for PL-R group. The median overall survival was 18.9 months (95% CI: 13.5-31.5); 27.7 months [17.8-43.3] for PL-S and 11.9 months [8.1-18.9] for PL-R group.
ConclusionCediranib shows significant activity in recurrent platinum sensitive OC. The toxicities were expected and manageable at the dose of 30 mg od.
OCRF has teamed up with Stand Up To Cancer, Ovarian Cancer National Alliance (OCNA), and the National Ovarian Cancer Coalition (NOCC) to fund an Ovarian Cancer “Dream Team,” which will conduct a large-scale research project to help change the future of ovarian cancer. The project will be spearheaded by Alan D’Andrea, MD (Dana-Farber Cancer Institute) and Elizabeth Swisher, MD (University of Washington), who is a member of the OCRF Scientific Advisory Committee and also an OCRF grantee.
The SU2C-OCRF-OCNA-NOCC Ovarian Cancer Dream Team, which was announced on April 20, 2015, will focus on “DNA Repair Therapies for Ovarian Cancer,” building on recent advances that have identified DNA repair as a common weakness in ovarian cancer. Researchers will also explore the prevention and early detection of ovarian cancer by developing a web-based approach to genetic testing and counseling. Dream Team researchers hope to offer women identified as genetically high-risk a choice of surgical options, including one that removes the fallopian tubes but spares the ovaries. The Dream Team grant will provide funding over a three-year period, starting in July 2015..........
Monday, April 20, 2015
Objectives: With IMRT and advanced radiation planning, anatomy and contouring is becoming increasingly important in the field of radiation oncology. The use of iodinated computed tomography (CT) contrast for radiation simulation CT scans can help define anatomy more precisely and thus improve contouring. The major risks of CT contrast (which at least partly accounts for the aversion by some departments to its routine use) are contrast induced nephropathy and allergic-like reactions.
Results: The evidence of complications attributable to standard doses of contrast for diagnostic CT examinations is weak. The preponderance of data on contrast induced nephropathy has been compiled from interventional cardiology procedures, and the current guidelines regarding diagnostic CT contrast require extrapolation on mostly retrospective data. The evidence available suggests that CT contrast related adverse events are rare, and contrast related nephropathy most often spontaneously resolves without further decline in baseline renal function.
Conclusion: The current data regarding safety of CT contrast provides a limited foundation on which to make evidence-based recommendations. We have reviewed the literature on CT contrast. By following some simple algorithms CT contrast can be safely utilized.
Full Text: PDF
Sunday, April 19, 2015
Women 50–59 years of age at time of randomization to CEE or placebo in the WHI Estrogen-Alone Trial were similar in median age to women initiating hormone replacement therapy in clinical practice. In the intervention phase, for women 50–59 years of age with CEE, there was an increased risk of DVT, gall bladder disease, and stroke, while the reduction in MI, invasive breast cancer, and global index of events was not statistically significant. With cumulative 13-year long-term follow-up, women 50–59 years of age with CEE showed a reduction in MI, as well as a reduced global index of events. The increased risk of stroke and DVT in the intervention phase for women 50–79 years of age, which did not show significant trends with age, declined with cessation of CEE. Long-term follow-up including at least 5 years of follow-up after completion of hormone therapy is necessary to optimally evaluate effects of hormone replacement therapy on cardiovascular, cancer, and mortality outcomes. Though a subgroup analysis does not provide an adequate basis for making guideline recommendations for primary prevention, the preponderance of evidence in the WHI Estrogen-Alone Trial strongly suggests an overall benefit with CEE with cumulative long-term follow-up in women 50–59 years of age. These potential benefits only apply to women with prior hysterectomy and for duration of CEE use similar to what was used in the trial. The WHI Estrogen-Alone Trial data does not provide information on longer durations of use and strongly suggests that initiation of hormone therapy at significantly later ages is harmful.
Friday, April 17, 2015
Note: study does not discuss Lynch Syndrome
"...These findings rationalize genetic testing for all women with ovarian cancer, which is currently not the standard of care. We need to inform women of the benefits of this option." "
The study "A targeted analysis identifies a high frequency of BRCA1 and BRCA2 mutation carriers in women with ovarian cancer from a founder population" was co-authored by Moria H. Belanger and Lena Dolman of McGill University; Suzanna L. Arcand of the RI-MUHC; Zhen Shen and George Chong of the Jewish General Hospital; Anne-Marie Mes-Masson and Diane Provencher of Centre de recherche du Centre Hospitalier de l'Université de Montréal and Institut du cancer de Montréal; and Patricia N Tonin of the RI-MUHC and McGill University.
Genetic variability in drug transport, metabolism or DNA repair affecting toxicity of chemotherapy in ovarian cancer
BACKGROUND:This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer.
METHODS:Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival.
RESULTS:The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1, A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1, T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004, OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T > C; p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1, A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free interval (p = 0.016).
CONCLUSIONS:Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer.
.....The past several years have seen increasing calls for an ecumenical approach to clinical research, with more flexible standards for what counts as acceptable study designs. Physicians have developed new methods to extract robust analyses from patient registries and from the ever-growing databases provided by electronic medical records. Will this erode the status of RCTs as a gold standard? The rise of personalised medicine, meanwhile, might make it more difficult to defend gold standards in diagnostic and therapeutic practice. Personalised medicine refocuses clinical attention away from the “typical” patients analysed by RCTs and onto the idiosyncrasies, genetic or otherwise, of individual patients. Has the phrase outlived its usefulness in medicine? It is too soon to tell. Yet even as some physicians turn away from their commitment to medical gold standards, some politicians, newly wary about global financial turbulence, talk of restoring the financial gold standard. Gold standards, whether actual or figurative, represent structures of exchange and aspirations toward stability, despite developments that threaten both.