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Dr. Donald F. Gleason, who developed the Gleason prostate cancer scoring system, died on December 28 in Edina, MN. The scoring system helps physicians determine the aggressiveness of prostate cancer, and the Gleason score is considered the most reliable indicator of the potential for prostate cancer to grow and spread.
ASCO Urges KRAS Gene Testing for Colorectal Cancer
The American Society of Clinical Oncology (ASCO) recommended today that patients with metastatic colorectal cancer who are candidates for anti-EFGR therapy have their tumors tested for KRAS gene mutations. In a "provisional clinical opinion," ASCO recommends that patients with mutated forms of the KRAS gene should not receive the drugs cetuximab (Erbitux) and panitumumab (Vectibix), based on recent studies indicating that these drugs are only effective in patients with normal forms of the gene.
5-FU-Based Chemotherapy Cures Some Patients with Colon Cancer
Researchers from the Adjuvant Colon Cancer Endpoints (ACCENT) Group used individual patient data from 18 phase III trials of adjuvant fluorouracil-based chemotherapy for colon cancer to show that the regimens provide their survival benefit primarily by reducing the high risk of recurrence within the first 2 years after surgery. Read more > >
Validated Colorectal Cancer Risk Assessment Tool Available OnlinePhysicians can use the tool to help patients make decisions about screening and care
Colonoscopy Reduces Death from Cancer in the Left Colon, but Not the RightReasons for the difference are not clear
PLCO Update Suggests Positive Predictive Value of Prostate Screening Drops over TimeCancers found at baseline in the study were more aggressive than those found in subsequent screenings
Radiation Plus Hormone Therapy for Locally Advanced Prostate Cancer Improves SurvivalPatients experienced similar overall health and quality of life compared to hormone therapy alone
Researchers Learn Why Some Platinum Drugs Are Toxic to Ear TissueThe study compared cisplatin and oxaliplatin in guinea pigs
Director's Update: Resource Digs Deep into NCI's Research Funding
NCI recently launched a newly enhanced Funded Research portal on its Web site. For a decade or more visitors to www.cancer.gov could search the cancer research portfolio, but the enhanced portal now provides consolidated information from varying NCI locations on one site, including funding and other data on NCI's intramural research program. The result is a significant increase in public access to this broader range of data. Read more > >
Special Report: Genome Studies Yield Insights into Childhood LeukemiaChanges to the IKAROS gene may help explain why chemotherapy fails some patients with ALL and could lead to a prognostic test
Spotlight: Looking to Refine HER2-targeted TherapyResearchers are investigating better ways to identify the best candidates for HER2-targeted therapy
Featured Clinical Trial: Immune System Reconstitution Following Unrelated HSCT and GVHD PreventionHow does the immune system regenerate following hematopoietic stem cell transplantation from an unrelated donor and graft-versus-host disease prevention?
Community Update: ASCO Proposes Strategies for Oncology Workforce ShortageUtilizing more non-physician practitioners may help meet patient needs
FDA Update
- New Prostate Cancer Drug Approved
- Gardasil Indication for Men Reviewed
- A Warning for Bone Density Drug
CMS Update
- CMS Proposes Expanding Medicare Coverage of PET Scans in Cancer Patients
- NCI Scientists Receive 2008 HHS Awards
- NCI Holds Annual Intramural Scientific
- New Issue of CCR Connections Released
- NCI Scientists Receive 2008 HHS Awards
The NCI Cancer Bulletin is produced by the National Cancer Institute (NCI), which was established in 1937. Through basic, clinical, and population-based biomedical research and training, NCI conducts and supports research that will lead to a future in which we can identify the environmental and genetic causes of cancer, prevent cancer before it starts, identify cancers that do develop at the earliest stage, eliminate cancers through innovative treatment interventions, and biologically control those cancers that we cannot eliminate so they become manageable, chronic diseases.
For more information about cancer, call 1-800-4-CANCER or visit http://www.cancer.gov.
NCI Cancer Bulletin staff can be reached at email@example.com.
Featured Article
5-FU-Based Chemotherapy Cures Some Patients with Colon Cancer
For several decades, chemotherapy regimens based on the drug fluorouracil (5-FU) have been part of the treatment for high-risk stage II or stage III colon cancer. Many clinical trials have shown that these regimens improve overall survival, but how they affect the risk of recurrence over time has not been clear.
In a study published online January 5 in the Journal of Clinical Oncology, researchers from the Adjuvant Colon Cancer Endpoints (ACCENT) Group used individual patient data from 18 phase III trials of adjuvant 5-FU-based chemotherapy for colon cancer to show that the regimens provide their survival benefit primarily by reducing the high risk of recurrence within the first 2 years after surgery.
By 5 years after treatment with 5-FU-based adjuvant chemotherapy, the risk of recurrence dropped to 1.5 percent, and dropped again to 0.5 percent by 8 years after treatment. Instead of delaying recurrence, "5-FU-based chemotherapy truly eradicates the disease and results in long-term cure in some patients," explained Dr. Daniel Sargent, professor of biostatistics and oncology at the Mayo Clinic and lead author of the study.
Measuring True Risk of Recurrence over Time
The ACCENT investigators reviewed survival data from 8 years of follow up for 20,898 patients in the 18 trials. Instead of the Kaplan-Meier method usually used to calculate survival after treatment, the investigators used a system called hazard-rate estimation, which requires a large data set but provides results that are easier to interpret. Hazard-rate estimation "allowed us to estimate and graphically present the true risk of recurrence at any given time" after treatment, said Dr. Sargent.
Out of the 20,898 patients, 35 percent had their cancer recur during 8 years of follow up, and 38 percent died from any cause during the same time period. For both patients who did and did not receive chemotherapy, "most relapses [occurred] in the first 2 years after surgery," stated the authors. However, the risk of death remained lower during that period of time and during the entire 8 years of follow up for patients who had received chemotherapy.
Overall, adjuvant chemotherapy with an 5-FU-based regimen improved 8-year overall survival by 7 percent (5 percent for patients with stage II cancer and 10 percent for patients with stage III cancer).
Implications for Follow-up Care
The authors cautioned against extending these results to newer combinations of chemotherapeutic and biologic drugs that do not contain 5-FU. "Longer-term follow up is likely to be required to establish a long-term survival benefit," they explained. The ACCENT group plans to update their analysis with data from newer treatment regimens as they become available. Dr. Sargent pointed out that "such analyses are only possible through individual clinical trialists making their data available for such pooled or meta-analyses, which has been made increasingly possible due to improvements in technology and by standardization of clinical trial data elements."
The results from the current study have important implications for follow-up care of patients with stage II or III colon cancer, he noted. "The risk of a patient's disease returning is highest in the first 2 years, and therefore the patient and their physician have to be very vigilant in their follow up during that period to make sure that if the cancer does come back, it is detected quickly.
"After 5 years and particularly after 8 years, the risk of the patient's disease coming back is very, very low, and physicians can then turn their attention to other priorities for that patient," he said.
—Sharon Reynolds
Cancer Research Highlights
Validated Colorectal Cancer Risk Assessment Tool Available Online
NCI researchers have developed one of the first colorectal cancer (CRC) absolute risk assessment models for people aged 50 to 85 without known genetic susceptibility to the disease, using data from two large case-control studies and validating the model in the NIH-AARP Diet and Health Study population. The tool uses answers about lifestyle, screening, and family history of CRC to calculate a person's 5-year, 10-year, and lifetime risk of developing the disease. Both the development and validation papers were published December 29 in the Journal of Clinical Oncology, and an online risk assessment tool based on the model is now available for use by physicians at http://www.cancer.gov/ColorectalCancerRisk/.
"This colorectal cancer risk model provides physicians and their patients with a new tool to help make informed decisions about colorectal cancer screening and other prevention strategies. It may also assist policy makers in evaluating the usefulness of current and future population colorectal cancer prevention approaches," said Dr. Andrew Freedman, lead author of the study, in an accompanying press release.
Dr. Freedman of NCI's Division of Cancer Control and Population Sciences and Dr. Ruth Pfeiffer of NCI's Division of Cancer Epidemiology and Genetics (DCEG) led the team that developed the model using data from two population-based, case-control studies, one for colon cancer and one for rectal cancer, and cancer incidence rates from the SEER database. Since non-Hispanic white men and women aged 50 years or older made up the majority of participants in both case-control studies, the researchers restricted their model to this group.
They determined the relative risks for a cancer diagnosis in three different areas of the colon and rectum based on known risk factors, including history of CRC screening, body mass index, and family history of CRC. The researchers also constructed a short risk-assessment patient questionnaire that easily captures the information used in the model.
To assess the model's performance, the researchers, led by DCEG's Dr. Yikyung Park, used the model to estimate the number of CRC cases expected in the 155,345 men and 108,057 women in the NIH-AARP cohort. They then compared those results to the actual number of cases diagnosed in that cohort between 1995 and 2003. They found that their model was well calibrated, with the estimated-to-observed ratio for CRC diagnoses being 0.99 in men and 1.05 in women.
The researchers are in the process of updating the Web tool with data from SEER to improve accuracy for other racial and ethnic groups.
Colonoscopy Reduces Death from Cancer in the Left Colon, but Not the Right
In a large case-control study performed by researchers at the University of Toronto, patients who had undergone colonoscopy at least once were significantly less likely to die of colorectal cancer (CRC) arising in the left side of the colon (the part of the colon closest to the rectum) than patients who had never had a colonoscopy. However, colonoscopy did not reduce mortality from CRC in the right side of the colon, according to results published in the December 15 Annals of Internal Medicine.
Using four Ontario-based databases, the investigators matched 10,292 patients who had died of CRC with 51,460 controls who did not have CRC. Each patient was matched to five controls by age, sex, income, and location of residence, and all controls were alive at the date of the patient's death.
Because the investigators could not distinguish screening colonoscopies from diagnostic colonoscopies using the database records, they excluded all colonoscopies done within 6 months before a diagnosis of CRC.
Seven percent of case patients and almost 10 percent of controls had undergone colonoscopy. "Case patients were less likely than controls to have undergone any attempted colonoscopy…or complete colonoscopy," stated the authors. Both attempted and complete colonoscopy reduced the likelihood of death from left-sided CRC, but not right-sided CRC.
The reasons for the lack of efficacy in preventing right-sided CRC are not clear, but may include less effective bowel preparation or colonoscopy technique in the right colon or differences in the biology and natural history of cancer arising in the right colon, explained the authors.
These results "seem consistent with a CRC mortality risk reduction of about 60 percent to 70 percent for the left colon and highlight the fact that we have very little data…about efficacy in the right colon," said Dr. David Ransohoff of the University of North Carolina at Chapel Hill, in an accompanying editorial.
PLCO Update Suggests Positive Predictive Value of Prostate Screening Drops over Time
Also in the News
In the most recent update of prostate cancer screening data from NCI's PLCO trial, the number of positive screening tests among the more than 38,000 men enrolled in the intervention arm has remained consistent during the 4 years of study. However, the positive predictive value of these tests—that is, the ratio of true positives to the total number of true and false positives—decreased over time. The full report appeared in the December issue of the British Journal of Urology International.
Researchers attributed this decrease in the positive predictive value from baseline screening, which was 17.9 percent, to the subsequent annual screens, which ranged from 10.4 percent to 12.3 percent, to the fact that initial screening identified many of the cancers and left men with elevated prostate-specific antigen (PSA) levels but negative biopsies to be identified in subsequent screening rounds. The cancers found at baseline were more likely than those found in subsequent screenings to be advanced stage (5.8 versus 2.9 percent) and to have a Gleason score of 7 to 10 (34 versus 25.5 percent).
PLCO is one of two major ongoing trials expected to show whether screening for prostate cancer saves lives. The other is the European Randomized Study of Screening for Prostate Cancer (ERSPC), which screens participants less frequently, at 2- and 4-year intervals. In a related commentary, ERSPC director Dr. Fritz H. Schröder addressed the issue of more aggressive prostate cancer, noting that the data in both trials "suggest that certain cancers escape screening irrespective of the screening interval used."
Radiation Plus Hormone Therapy for Locally Advanced Prostate Cancer Improves Survival
A randomized clinical trial, published online December 15 in The Lancet, that tested hormone therapy (HT) alone versus HT plus radiation therapy (RT) for locally advanced prostate cancer adds to the body of evidence that adding RT to HT is more effective than HT alone for this group of patients.
Investigators from two European research groups, led by Dr. Anders Widmark of Umeå University in Sweden, assigned 875 men with locally advanced prostate cancer—cancer that had invaded local tissue but had not spread to the lymph nodes or distant sites—to receive either HT alone or HT plus standard 3D conformal RT. HT consisted of leuprorelin (known in the United States as leuprolide) given for 3 months and flutamide given until disease progression or death. Patients could switch to the drug bicalutamide if they experienced unacceptable side effects while taking flutamide.
After a median follow up of 7.6 years, 18 percent of the men in the HT group had died of prostate cancer compared to 8.5 percent of the men in the HT-plus-RT group. Ten-year mortality from prostate cancer was 23.9 percent for men in the HT group versus 11.9 percent in the HT-plus-RT group.
Follow-up visits revealed "a small but significant increase of moderate to severe late effects related to urinary and sexual function" in the HT-plus-RT group, stated the authors. However, patients did not report significant differences in their overall health and quality of life on surveys taken 4 years after treatment, with the exception of social function, which was decreased in the HT-plus-RT group.
Researchers Learn Why Some Platinum Drugs Are Toxic to Ear Tissue
Ototoxicity, or damage to inner-ear cells that detect sound, is a known side effect of platinum-based chemotherapy drugs. The damage is much more common with cisplatin than with oxaliplatin, though the reason for this difference has been unknown. Swedish researchers have now tested some of the possible explanations by comparing the activity of these two drugs in the inner ears of guinea pigs. Their analysis appeared December 30 in the Journal of the National Cancer Institute.
Cisplatin and oxaliplatin are thought to work by attaching to DNA and binding the genetic material so that it cannot replicate properly, thereby preventing cell division. But because the cells in the inner ear are already differentiated and less susceptible to this mechanism, the researchers hypothesized that cisplatin and oxaliplatin may also have an effect outside of the nucleus by generating reactive oxygen species, or free radicals.
They cultured colon carcinoma cells and measured the extent to which each drug induced cell death, or apoptosis, and found that cisplatin is significantly more dependent on free radicals than is oxaliplatin for triggering death in these cells. Guinea pigs showed more signs of free radical-induced apoptosis in their cochlea after exposure to cisplatin than to oxaliplatin.
The two drugs also showed marked effects on the transmission of sound signals from the cochlea to the brain, with cisplatin causing more damage to the hair cells that detect vibrations, and ultimately causing deafness, while comparable exposure to oxaliplatin did not. Cisplatin absorbed into the inner ear more easily than oxaliplatin did, and it remained in the tissues for a longer time.
"[It] should not be taken for granted that human subjects have the same cochlear pharmacokinetics [as guinea pigs]," the researchers noted, though they believe that the major aspects of their conclusions are valid for humans.
Director's Update
Resource Digs Deep into NCI's Research Funding
It is critically important that scientific investments made by NCI be transparent, ensuring accountability of the Institute and providing essential information to the entire cancer community who tirelessly advocate on behalf of patients. Since its creation in 1937, NCI has been tracking its research portfolio and over time has developed a robust system for coding each research project the Institute supports. NCI uses highly trained, experienced indexers who carefully review each grant to ensure that a given project's scientific contributions are accurately captured, allowing the dollars associated with the project to be assigned to specific categories.
The importance of ensuring that the public has ready access to the scientific investments made by NCI, and the results of those investments, has been articulated in legislation numerous times over the past three decades. While NCI has focused on the rigors of the scientific coding process, the same level of attention was required to report its research investments in a clear and comprehensive manner. To address this, NCI recently launched a newly enhanced Funded Research Portfolio on its Web site.
Since 1998, visitors to NCI's Web site, Cancer.gov, could search the cancer research investments made by the Institute, but often data had to be obtained from multiple sources. The enhanced portal now provides consolidated information on one site, including funding and other data on NCI's intramural research program, grants to extramural scientists, and research contracts. The result is significantly improved access to this broader range of data and enhanced user-friendliness of the portal. Users can navigate to the funded research database from various points on NCI's Web site, including the "Research and Funding" tab along the top of the home page or the "Science Serving People" or "Director's Corner" portals.
The data can be searched using individual disease categories or conditions, or via a more overarching approach that can include a variety of parameters such as year, disease category, disease condition, key word, etc. Search results include all of the research projects and grants covered by those criteria, with links to the abstracts that outline the methodology and goals of each project or grant.
Users can also select one of two ways to view the output of their searches: a detailed "coding" report that shows all of the codes NCI's expert indexers used to categorize each research project or grant, or a budget report that reveals the pro-rated funding for each project and the proportional relevance of that research to a given cancer type. In either case, users can then export their reports into a Microsoft Excel spreadsheet.
We are also concentrating our efforts on building analysis tools. One area on which there will be an ongoing focus, for example, is how to both define and incorporate "outcomes" into the research portfolio, including things like published papers, impact factors of publications, grant renewals, and changes to laboratory and clinical practice brought about by these investments. NCI is working with other NIH institutes to understand how they utilize evolving tools to conduct portfolio analysis and to determine if there are ways that we can work collectively to better demonstrate the return on investment for NCI funding.
Finally, let me emphasize that this enhanced resource is a work in progress, and we are integrating feedback from formal user testing sessions into plans for future improvement. We are actively seeking input on how to make the Funded Research Portfolio even more useful and accessible, and we encourage users to submit their comments on this resource to email@example.com. We are committed to refining this resource to meet the broad needs of the cancer community and using this tool to better communicate the investments in cancer research being made on behalf of the American people.
I hope you find this tool helpful. We believe it is another important way to connect you with your NCI.
Dr. John E. Niederhuber
Director, National Cancer Institute
Special Report
Genome Studies Yield Insights into Childhood Leukemia
The vast majority of children treated for acute lymphoblastic leukemia (ALL) survive the disease. But the standard treatments fail in about 20 percent of cases, and the reasons are not always understood. A new study suggests that changes to a gene called IKAROS (or IZKF1) may help explain why chemotherapy fails some patients with ALL.
An analysis of patients' DNA and health records revealed that the IKAROS gene was mutated or deleted in two independent groups of ALL patients who had high rates of relapse. These children, the researchers concluded, may have a previously unrecognized subtype of ALL with a very poor prognosis.
If confirmed, the discovery could lead to genetic tests that identify children at high risk of relapse who may benefit from more aggressive treatments. ALL is a cancer of the blood, and IKAROS plays a role in the development of the cells that are abnormal in the disease.
"This study is an important first step toward learning how to treat ALL patients better and attaining our goal of curing all children with leukemia," said coauthor Dr. Stephen Hunger of the University of Colorado Denver School of Medicine and chair of the Children's Oncology Group ALL Committee. "To improve the outcomes for patients who do not respond to treatment, we need to better understand how their leukemias differ from those of children who do."
Results from TARGET
The IKAROS findings, which were published online in the New England Journal of Medicine last week, are the first results from the Childhood Cancer TARGET Initiative. TARGET is an NCI-supported project that brings together investigators with expertise on childhood cancers and genome analysis. The ALL study included investigators from St. Jude Children's Research Hospital, the Children's Oncology Group, the University of New Mexico Cancer Research and Treatment Center, and NCI.
Using state-of-the-art technologies, the team screened ALL cells for gains and losses of DNA, profiled their gene activity, and sequenced selected genes. By integrating these results and information about each patient's clinical course, the researchers uncovered a potential contributing factor to poor outcomes in ALL.
"We were able to accelerate the pace of discovery substantially and to identify a previously unknown group of ALL patients at risk for treatment failure," said coauthor Dr. Malcolm Smith of NCI's Cancer Therapy Evaluation Program and an NCI leader of the TARGET Initiative.
One major identifier of high-risk ALL has been the Philadelphia chromosome, and some researchers have wondered whether there were other comparable lesions associated with poor outcome. "We now know that there are, and the IKAROS deletion provides an opening for further exploring the biology of this subtype of high-risk ALL," said Dr. Smith.
The Same Gene
The discovery builds on a report published last year showing that IKAROS is often deleted in a specific subset of ALL patients at high risk of treatment failure—those who carry the Philadelphia chromosome. IKAROS, it now appears, may be altered in children who lack the Philadelphia chromosome but who also have a high risk of relapse.
"Here we have two subtypes of leukemia that share some but not all of the same genetic changes," said Dr. Charles Mullighan of St. Jude, the study's first author. "Our results suggest that IKAROS has a fundamental role in the behavior of these leukemias."
The researchers are not recommending that physicians test IKAROS in ALL patients at this time. Dr. Mullighan noted that it is not clear which types of deletions and mutations are most relevant to prognosis, and more research is needed in additional populations.
Nonetheless, knowing that IKAROS deletions occur in a second subtype of high-risk ALL "helps us to better understand the genetic heterogeneity of the disease," said Dr. Hunger.
Counting Copies
Gains and losses of DNA—also known as copy number changes—have been reported in ALL, but it has not been known whether they influence patient outcomes. Using high-resolution microarrays and cells from 221 patients with high-risk ALL, the researchers detected copy number changes in 50 chromosome regions.
The most striking finding was the association between IKAROS changes and poor outcome. The relapse rate was approximately 75 percent for patients with IKAROS alterations, which is extremely high for ALL, noted Dr. Mullighan. This was confirmed in another group of 258 children with ALL who were treated at St. Jude.
When the team profiled gene activity in ALL tumors, they discovered patterns like those of Philadelphia chromosome-positive ALL, which involves an overactive kinase protein. The similarity suggests that an overactive kinase protein may play a role in the new subtype, a theory the TARGET team is now investigating. Kinases have been the basis for successful cancer drugs such as imatinib (Gleevec).
A Gold Mine
Although changes to IKAROS may play a central role in some forms of ALL, other genes are also involved. The investigators are now cataloguing the molecular changes in the new subtype and intend to publish more results later this year.
"This is really just the beginning of what we are going to learn," said coauthor Dr. Daniela S. Gerhard, who directs NCI's Office of Cancer Genomics and is an NCI leader of the TARGET Initiative. The project has a wealth of biological and clinical information on these patients that can be a resource as new discoveries emerge, she explained. In the meantime, the data are available to researchers online at the TARGET Web site.
Dr. Gerhard is also a leader of The Cancer Genome Atlas (TCGA) project, which employs a similar approach and has shared tools and resources with the TARGET investigators. "In terms of providing a foundation for personalized medicine, the ability to integrate genomic data and clinical information in this way has been a goldmine," she said.
—Edward R. Winstead
Looking to Refine HER2-targeted Therapy
When is a patient a candidate for a targeted therapy? That's a question some breast cancer researchers are attempting to answer in the wake of results from several studies presented in 2007 that suggested the definition of HER2-positive—that is, women whose breast tumors produce an excess of the HER2 protein—may be too strict. These retrospective studies showed that even women who were HER2-negative benefited from the HER2-targeted agent trastuzumab (Herceptin).
A monoclonal antibody, trastuzumab has been one of the most frequently cited success stories of the early era of molecularly targeted therapies. Its use improves progression-free and overall survival in women with HER2-positive metastatic breast cancer, and current data suggest it has a dramatic impact on the likelihood of cure for women with early stage HER2-positive disease.
Not all of the studies that continue trickling into the literature support the findings from those 2007 studies, but there is enough evidence, argued Dr. Peter Kaufman, professor of medicine at the Norris Cotton Cancer Center at the Dartmouth Hitchcock Medical Center, to suggest "that we may need to rethink conventional dogma."
Hints of Something, but What?
Breast cancer experts agree that the recent studies are hypothesis-generating and should not dictate current clinical practice. After all, choosing breast cancer patients' treatment based on HER2 status has been a successful paradigm, said Dr. Laura Esserman, who directs the breast cancer program at the Helen Diller Comprehensive Cancer Center at the University of California, San Francisco.
"In general, targeting HER2 has proven to be the right thing to do," she said. "I think it's pretty clear that we've done a good job. It hasn't been perfect, though. There's room for improvement."
The Measure of a Target
IHC (immunohistochemistry) and FISH (fluorescence in situ hybridization) are the two testing methods recommended in the ASCO/CAP HER2-testing guidelines, which detail how the tests should be performed and what constitutes HER2-positive, -negative, and equivocal or borderline results. The IHC assay measures the amount of HER2 protein expressed in cancer cells, while the FISH assay measures either the total number of copies of the HER2 gene in a tumor cell or the ratio of HER2 genes to chromosome 17 copies.
|FISH (two approaches)
|<6 HER2 copies per cell or HER2:ch 17 ratio of 2.2 to 1
|0+, 1+
|<4 HER2 copies per cell or HER2:ch 17 ratio <1.8 to 1
|4 – 5 HER2 copies or 1.8 – 2.2 HER2:ch 17 ratio
For example, researchers would like to find ways to improve the response rate to trastuzumab, which hovers between 25 and 30 percent. There are also misgivings about the accuracy of HER2 testing, concerns that were significant enough to prompt the American Society of Clinical Oncology (ASCO) and College of American Pathologists (CAP) to develop clinical guidelines for HER2 testing.
"This is a tumor marker that's being used as the sole determinant of therapy selection," explained the guidelines panel co-chair, Dr. Antonio C. Wolff of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. "That's why it's important that pathologists do their best to adhere to the guidelines and clinicians ask questions about the quality of testing."
It's also critical to continue clinical research on the use of HER2-targeted therapies like trastuzumab and lapatinib (Tykerb), Dr. Wolff added. "You need to be confident that you're talking about true HER2-positive or -negative tumors. Then you can start looking at clinical outcomes," he said.
The response rate and accuracy issues overlap with the questions about the definition of HER2-positive, which is most commonly determined with two tests, IHC and FISH. (See sidebar.)
The IHC and FISH cutoffs that correspond with response to trastuzumab were established based on clinical trials involving women with metastatic breast cancer, explained Dr. Tracy Lively, associate chief of the Diagnostics Evaluation Branch in NCI's Division of Cancer Treatment and Diagnosis. The recent data, she added, suggest that perhaps those cutoffs may need to be modified for women being treated for early stage disease.
At the 2007 ASCO annual meeting, Dr. Soonmyung Paik, director of the Division of Pathology for the National Surgical Adjuvant Breast and Bowel Project (NSABP) in Pittsburgh, first suggested the same thing. Dr. Paik and his colleagues had conducted an unplanned, retrospective analysis of available tumor samples from the B-31 trial, which compared adjuvant chemotherapy and trastuzumab to chemotherapy alone in women with HER2-positive, early stage breast cancer.
After retesting the tumor blocks, they found that 10 percent were truly HER2-negative (meaning the women shouldn't have been enrolled in the trial). Nevertheless, there was a statistically significant trend toward improved outcomes in HER2-negative patients treated with trastuzumab. In fact, every HER2-negative patient subset saw some benefit, although not all reached statistical significance.
The findings were consistent with data from two other studies presented at the meeting, including another unplanned, retrospective analysis led by Dr. Kaufman of tumor samples from women with metastatic breast cancer in the CALGB 9840 trial. Some women in the trial whose tumors were HER2-negative according to FISH but who also had polysomy of chromosome 17—extra copies of chromosome 17, where the HER2 gene resides—had improved response rates to treatment with trastuzumab and chemotherapy compared to chemotherapy alone.
"That raised a fair number of eyebrows," Dr. Kaufman said. "But, again, these findings are preliminary. It could just be a fluke due to the small sample size and retrospective analysis."
Data on this topic continue to emerge, including a recent study led by Dr. Michael Press from the Norris Comprehensive Cancer Center at the University of Southern California, which found no benefit from lapatinib in HER2-negative women.
Where to Go from Here
A large clinical trial is needed to determine whether some women, whose tumors reside somewhere in the molecular middle between HER2-negative and -positive, could benefit from HER2-targeted therapy, said Dr. Lively.
Such a study could be on the horizon. A validation study to confirm the results from Dr. Paik's earlier study "is moving forward quickly," explained NSABP Director of Medical Affairs Dr. Charles Geyer. If the results are positive, he continued, NSABP plans to conduct a clinical trial that would look at whether women with breast tumors that fall into a "HER2-low" category may benefit clinically from HER2-targeted therapy.
In the meantime, Dr. Esserman said, although the available data have raised some tough questions, she sees a positive side.
"It's not necessarily that these assays are wrong," she said. "Maybe there's just a better way to measure."
Dr. Esserman, for instance, is a co-principal investigator of a clinical trial of neoadjuvant chemotherapy for women with early stage breast cancer called I-SPY. The trial is using molecular analyses of serial biopsies and serial MRI scans to identify markers of response to treatment. One area showing promise, she noted, is the correlation of the levels of phosphorylated HER2 protein (the addition of phosphate groups to the protein, which regulates its activity) with other measures of HER2 expression and response to trastuzumab.
Much further along the clinical spectrum is an assay developed by San Francisco-based Monogram Biosciences called HERmark. According to the company, the assay provides a more exact measurement of HER2 levels, as well as the extent of the complexes formed by HER2 proteins on the surface of cancer cells (called dimers). Smaller studies presented at national meetings have suggested the assay can more accurately predict which women, including those who are HER2-positive, will respond to trastuzumab.
"Without the controversy," Dr. Esserman said, "I don't think there would be as much motivation to develop new and better assays."
—Carmen Phillips
Featured Clinical Trial
Studying Immune System Reconstitution Following Unrelated Donor Transplantation and Graft-Versus-Host Disease Prevention
Name of the Trial
Phase I/II Randomized Pilot Study of Targeted Immune-Depleting Chemotherapy, Reduced-Intensity Allogeneic Hematopoietic Stem Cell Transplantation from an HLA-Matched Unrelated Donor, and Graft-Versus-Host Disease Prophylaxis Comprising Tacrolimus, Methotrexate, and Sirolimus versus Alemtuxumab and Cyclosporine in Patients with High-Risk Advanced Hematologic Malignancies or Other Diseases (NCI-07-C-0195). See the protocol summary.
Principal Investigators
Dr. Michael Bishop and Dr. Steven Pavletic, NCI Center for Cancer Research
Why This Trial Is Important
Allogeneic hematopoietic stem cell transplantation (allogeneic HSCT) is one of the few potentially curative therapies available to patients with some advanced leukemias, lymphomas, or other blood or bone marrow diseases (collectively known as hematologic malignancies). In allogeneic HSCT, patients first receive high-dose chemotherapy and/or radiation therapy to destroy their hematopoietic stem cells; then, stem cells from a donor, either a relative or an unrelated volunteer, are used to restore bone marrow function.
Unrelated Donors Help Save Lives
This week's Featured Clinical Trial focuses on restoration of the immune system in patients receiving blood-forming stem cells from unrelated donors. According to principal investigator Dr. Michael Bishop, only 1 in 4 patients who can be helped by a donor stem cell transplant has a suitable related donor available, so unrelated donors play an important role in permitting patients to receive this potentially life-saving therapy.
For more information about donating stem cells, visit the National Marrow Donor Program Web site.
Many patients undergoing allogeneic HSCT receive prophylactic treatment with immunosuppressive or other drugs to prevent graft-versus-host disease (GVHD), a common and potentially serious complication of allogeneic HSCT. GVHD occurs when transplanted cells (the graft) attack the recipient's (the host's) organs and tissues. The effects of GVHD-prevention therapies on immune system reconstitution following allogeneic HSCT are not well understood.
In this clinical trial, patients with high-risk (refractory or progressive), advanced hematologic malignancies will undergo chemotherapy to induce remission; those achieving remission will then undergo reduced-intensity, immune-depleting chemotherapy followed by allogeneic HSCT from a matched, unrelated donor. After HSCT, the patients will be treated with one of two distinct drug regimens that are currently used to prevent GVHD. The researchers will assess the effectiveness and safety of these treatments and examine how the immune system rebuilds itself in these patients.
"The drugs used to prevent GVHD have a significant effect on how the immune system regenerates after stem cell transplant," said Dr. Bishop. "Our purpose with this trial is to study how two proven GVHD-prevention regimens affect immune reconstitution following transplantation from unrelated donors, and then, based on the knowledge we gain, to design future trials to enhance immune system recovery, further reduce toxicity, and strengthen the antitumor activity of HSCT."
For More Information
See the lists of entry criteria and trial contact information or call the NCI Clinical Trials Referral Office at 1-888-NCI-1937. The call is toll free and confidential.
An archive of "Featured Clinical Trial" columns is available at http://www.cancer.gov/clinicaltrials/ft-all-featured-trials.
Community Update
ASCO Proposes Strategies for Oncology Workforce Shortage
The Oncologist Workforce by the Numbers
- Nearly 70 percent of oncology visits are for patients 1 year or more post diagnosis
- 76 percent of patients receive chemotherapy only in a medical office
- 50 percent of practicing oncologists are age 50 or older
By 2020:
- Cancer incidence is expected to increase by 50 percent
- The number of survivors, currently at 12.1 million, is expected to increase by 81 percent
- 6,400 oncologists will be age 65 or older
The American Society of Clinical Oncology (ASCO) is calling for the development of "innovative practice arrangements" and an expansion of oncology fellowship programs to help ease the impact of a forecasted shortage of oncologists in the United States by 2020.
The steps are outlined in a new strategic plan released by the organization in November 2008. The plan was prompted by a 2007 ASCO-fund report by the Association of American Medical Colleges (AAMC) that projected a shortfall of as many as 4,080 medical oncologists by the end of the next decade.
The cause of the forecasted shortage is multi-fold, explained Dr. Dean Bajorin of Memorial Sloan-Kettering Cancer Center, a co-chair of the working group that developed the strategic plan. But the primary causes driving the shortage are clear.
"Our country is getting older," Dr. Bajorin said. "As the population ages, we will have more cases of cancer. The second aspect is that we're getting better at treating cancer. More and more patients are surviving and they are surviving longer."
Other factors are at play, including stagnation in the growth of oncology fellowship programs due in large part to a lack of funding, the 2007 ASCO/AAMC report concluded.
Among the changes to clinical practice advocated in the strategic plan, Dr. Bajorin said, is the expanded use of so-called nonphysician practitioners (NPPs) such as oncology nurses, nurse practitioners, and physician assistants.
According to Dr. Betty Ferrell, from the City of Hope Cancer Center and co-chair of an Institute of Medicine (IOM)-sponsored workshop on the oncology workforce held last year, the time for such arrangements has already arrived.
"Much of medical oncologists' time is now spent with cancer survivors or patients with advanced disease, and we're running into this dilemma where oncologists don't have as much time to see newly diagnosed patients," she said. In areas such as palliative care and survivorship, NPPs can provide valuable services, she stressed.
ASCO has launched a study to assess the extent to which these "physician extenders" are playing a role in oncology practices, and to determine their impact on the number of patients seen and the quality of care provided.
There are early clues about such arrangements from the surveys done as part of the 2007 workforce report, Dr. Bajorin explained. "Practices that used nurse practitioners and physician assistants were able to see more patients," he said. "It turned out to be a 'win-win-win' for everybody involved. The patients preferred that model. The NPPs liked the model, and the oncologists did, as well."
Other changes to clinical practice, Dr. Bajorin added, include finding ways to bring retired oncologists back into the workforce on a limited basis.
"The workforce problems we're having now are only going to get worse in the future," said Dr. Ferrell. Addressing the problem will require a broad range of activities, such as improved training for primary care physicians—a field that is already in the midst of a shortage—on meeting the unique needs of cancer survivors.
With established model programs in areas like training and palliative care, and the attention brought to topics like palliative care and survivorship through reports from the IOM and President's Cancer Panel, there is an opportunity to make much needed changes that could also improve the overall quality of cancer care, Dr. Ferrell said.
"We have an opportunity to solve some serious problems and to much better serve patients and survivors," she said.
—Carmen Phillips
FDA Update
New Prostate Cancer Drug Approved
The FDA recently approved the injectable drug degarelix for the treatment of advanced, hormone-sensitive prostate cancer. Developed by Ferring Pharmaceuticals, degarelix prevents tumor growth by blocking signals from the pituitary gland that trigger the release of testosterone. A phase III study comparing it with a similar drug, leuprolide (Lupron Depot), showed that degarelix was just as effective at lowering testosterone levels, though it did so more quickly than leuprolide.
Gardasil Indication for Men Reviewed
The FDA is reviewing an application for approval of the Merck & Co. vaccine Gardasil for use in males. Data for the review come from a study of 4,000 boys and men aged 16 to 26, in which the vaccine reduced the risk of external genital lesions by 90 percent, according to a company press release. Gardasil targets the two types of human papillomavirus that are most commonly linked to cancer, including cancers of the cervix, vulva, vagina, anus, penis, and head and neck, and two other types linked to genital warts. It is currently approved for use in girls and women aged 9 to 26 years.
A Warning for Bone Density Drug
The January 1, 2009 issue of the New England Journal of Medicine includes a letter from Dr. Diane Wysowski of the FDA's Division of Drug Risk Evaluation, citing reports of esophageal cancer and deaths in patients confirmed or suspected of taking the oral bisphosphonate alendronate (Fosamax) or other drugs in this class, which prevent bone weakness. In the United States, between 1995 and the middle of last year, 23 patients developed the disease and 8 died. In Europe and Japan, 31 patients developed esophageal cancer and 6 died. In some cases, these patients had Barrett esophagus, a known precursor to esophageal cancer.
"Esophagitis has been associated with oral bisphosphonates, usually when the drugs are not taken according to directions," wrote Dr. Wysowski. She warned that physicians should not prescribe oral bisphosphonates to patients who have Barrett esophagus and that the drugs should be considered possible risk factors for esophageal cancer.
CMS Update
CMS Proposes Expanding Medicare Coverage of PET Scans in Cancer Patients
The Centers for Medicare and Medicaid Services (CMS) has issued a national coverage determination (NCD) that would expand Medicare coverage of PET scans as an initial diagnostic test for cancer patients. Under an existing NCD issued in 2005, Medicare only covers such PET scans for certain cancers if the treating physician and patient agree to submit data on the scans to a clinical registry.
The registry, the National Oncologic PET Registry (NOPR), was organized as a result of a collaboration among CMS and several radiology- or cancer-related professional associations. It was the first such registry established under CMS' Coverage with Evidence Development program, the goal of which is "to develop evidence on the utilization and impact of the item or service evaluated in an NCD," according to a CMS statement.
The proposed NCD would lift the requirement for submission of data to the NOPR for the first PET scan intended to guide the course of a patient's treatment. The proposal follows an analysis of NOPR data published last spring, which found that PET scan results altered how physicians intended to manage patients more than one-third of the time, including the type of treatment they would prescribe.
CMS is accepting public comments on the proposed NCD through February 5, 2009.
NCI Scientists Receive 2008 HHS Awards
On January 6, four NCI scientists from the Center for Cancer Research (CCR) were honored by the Department of Health and Human Services with 2008 Departmental Awards.
Dr. Ira Pastan, of the Laboratory of Molecular Biology, was presented the Secretary's Award for Meritorious Service for his outstanding contributions to the development of immunotoxins against cancer. Drs. Douglas Lowy and John Schiller received the Hubert H. Humphrey Award for Service to America, for their contributions to the development of the first HPV vaccines. And Dr. Robert Wiltrout received the Career Achievement Award for exceptional leadership of CCR and consistently outstanding research in the immunology and cancer fields.
NCI Holds Annual Intramural Scientific Retreat
On January 8, NCI's intramural scientific investigators came together to share their research at the Annual Intramural Scientific Retreat. The retreat was an opportunity for investigators to interact with colleagues from different disciplines and to learn about the work being done in labs across the institute.
Over the course of the day, three award lectures were presented. Dr. Ira Pastan delivered the 5th Annual Alan S. Rabson Award Lecture for Intramural Research. Dr. Carol Prives of Columbia University presented the 8th Annual Rosalind E. Franklin Award Lecture for Women in Cancer Research, and Dr. Brian Druker, director of the Knight Cancer Institute at Oregon Health and Science University, spoke about translational research and his work developing imatinib (Gleevec) during the 13th Annual Alfred G. Knudson Award Lecture in Cancer Genetics.
Finally, a number of NCI scientists received NCI Director's Intramural Innovation Awards, which are designed to support the development of highly innovative approaches and technologies aimed at significant cancer-related problems.
New Issue of CCR Connections Released
NCI's Center for Cancer Research (CCR) recently released a new issue of their news magazine, CCR Connections. To view the Web version of Volume 2, Issue 2, please visit: http://home.ccr.cancer.gov/connections/index.asp.
In the latest issue, readers will find information on recent journal articles and staff awards, as well as a conversation with CCR's new chief of the Medical Oncology Branch; features on targeted imaging technologies, the DNA of drug discovery, and ovarian cancer; and a commentary by former CCR investigator Dr. Bruce Johnson.
CCR Connections is published biannually. Send a request for a print or online subscription to firstname.lastname@example.com.


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Me (40) DH (47) & furbabies * m/c 7/08 4/12 11/12
I confess these days of four+-hour commutes are completely exhausting me, mentally and physically. I was cranky all weekend because I was so tired and couldn't get caught up.
I thought the bridge would re-open on Friday afternoon, so I drove the long way around in the morning, and it took nearly 3 hours to get home. When I take public transit, it's about 2 hours each way. Sigh.
I thought that I was ready to move to adoption but we have put the process on hold. I don't think that I have quite given up yet on the idea of having a genetic baby....and now that I'm trying to lose weight again, maybe that will jumpstart things. Plus DH and I are not really that active so maybe a lot of the times I was trying to time it right, I wasn't. And I was worried that we might get a child and have bonding/attachment issues and I'm having a hard time justifying spending our pretty much entire savings for adoption. Plus my aunt is pushing us to think about foster care to adopt...which is how she got my cousins....in a few years if we still don't have a child.
So now that we just signed a year lease a few weeks ago, we are back to a house. We are looking at building next year....waiting to see if they extend the tax credit because if they do, we will try to build sooner and get it. If not, probably looking at having the house ready for next fall...usually takes 4-5 months to build.
We are chatting with one bank on Friday. Didn't think that it would be an issue because we were approved earlier this year for a 290k house and we are looking at about 180K to build. Until I found out that at least some banks are requiring 20-25% down for new construction. We were going to do 10-15% down...NOT 20.
So yeah I'm driving DH nuts because we have this money and can do adoption or a house....and I keep changing my mind on which I want more. He was joking with me and calling me Brett Farve (ok we are in WI and Packer fans so this is a definite dig).
Of course DH is not being helpful at all. He is ok with either and has no preference....well he does. His is to stay renting because it's cheap, he hates moving and likes to see his savings grow. So he just says for me to pick and he is good with either but just to make up my mind already and stop making his head hurt with the back and forth and talking about the same thing over and over.
He says what he really wants most is me to be happy.
I confess that it's November 3rd and I only have 400ish words for NaNoWriMo.
Ashley - I'm so happy that they're finally getting off your butt!!! Come on Charlie, put on some pudge! My friend's son is having trouble gaining weight, too, and her first pedi actually said that he'd rather the baby be on formula so he could have proof of how much he eats daily (as opposed to her denying him the boob? I don't get it )
Lydia - I totally thought of you and my other Bay Area friends when the bridge closed... I'm so sorry you guys had to deal with that!!! I can't even imagine... that thing is such an important part of everyone's commute.
Sorry you are so torn Jennifer. You have 2 very big totally different decisions to make.
I hope your bridge gets fixed ASAP!!! That is beyond unimaginable!
Last edited by rhiannasmoms43; 11-03-2009 at 10:49 AM.
Me: Julie-46 DH: Kelly-52 DD: Rhianna-17 DS: Gage-He's 3!
I confess -- Our vehicle is a "loaner" (of sorts) from my parents... My dad recently told me that DH was not allowed to drive it because he hasn't found a job yet. Well he had an interview yesterday, and my mom and I had plans at the same time, so he drove the truck to it. On his way to meet up with us, someone sideswiped him, and now we have to deal with all the insurance, etc........................ and calling my dad and telling him that DH was driving the truck........
I confess I'm here but totally exhausted. What's up?
Me (40) DH (47) & furbabies * m/c 7/08 4/12 11/12
I confess APA is way slow tonight. To liven things up, here's a cute kid comment from work today.
Me: What do you do with a toaster?
Kid: You put toaster strudels in it!
Me (40) DH (47) & furbabies * m/c 7/08 4/12 11/12
I'm off to read in bed, I think. I'm tired of being tired all the time!
Me (40) DH (47) & furbabies * m/c 7/08 4/12 11/12
I tried to hold Ronin and rock him to sleep and it's now been two hours and I gave up. I came out to the living room, dh went in there, and he lasted 10 minutes before coming out again. I handled Ronin's waking-up-every-hour for 15 months better than this. It's a new level of frustration. The other thing is that Claire goes to sleep quickly and easily, so I know it's just Ro's mind that can't shut down, and not anything specific I'm doing to screw up his sleep. Still, I can't help but wonder if I should be doing or should have done something different.
Also, the vaccine debates are driving me crazy.
That is all.
Lydia- must be something in the air. I was up ALL NIGHT between Savana and Kai. I got up for my day at 5:30 and I'm dragging. They are 2 and 4! When will they sleep through the night!? Savana ususally does actually but Kai is another story.
I confess that ;my mom gets the results of her latest scan today to see if the chemo treatments have been working on the cancer in her body. I am going nuts thinking about the possible outcomes. I just don't know if her emotional stability could take another blow. Or my dads. Between losing my cousin and finding out my dad's best friend has brain cancer, it has been a really rough two weeks for them.
I confess that Savana and Kai are driving me totally batty with their "poopy" talk. It's poopy this and poopy that all the time. I tell them I don't like it, and that it is bathroom talk. So the little stinkers go stand in the bathroom and say and say "poopypoopypoopypoopy" It's so annoying, but really that's all it is, so I know I need to just chill out and let it go but it BUGS me!
I confess that my cousin is getting married next weekend and it's a catholic ceremony which means really long with a full mass. I'ts a child friendly wedding but I'm nervous to bring Savana and Kai to the ceremony. They have never been to church and would not know why or how to sit still and be quiet for an hour. I'm considering leaving them and dbf at the hotel but I know my family will all be like, "Why didn't you bring them?" and I'm going to have to say "Um, because they have no idea how to act in church."
Last edited by Bridget; 11-04-2009 at 06:29 AM.
Your bridge is open! Hurray for shorter commutes!
Sorry about your mom. BTDT and it is terrible.
Me: Julie-46 DH: Kelly-52 DD: Rhianna-17 DS: Gage-He's 3!
I confess that I am going into menopause.
I confess that menopause is a nasty state to be in. I have been getting so wired up over the silliest things that I am grinding/clenching my teeth 24/7. I have actually broke 3 fillings because of this.
I confess that my cat came back! He has been gone since Halloween night and we had posters up, an ad in the newspaper, phoned all the vets/ animal control/ Humane society to leave his stats. He has a brutal cough that got 150% worse from being exposed to the elements (rain, hail, sub-zero temp) for the last 4 days, but he is home and eating like a horse
Last edited by rhiannasmoms43; 11-04-2009 at 07:51 AM.
Me: Julie-46 DH: Kelly-52 DD: Rhianna-17 DS: Gage-He's 3!


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Ekta Kapoor first established herself as a successful producer on the small screen and then transitioned into films with equal success. The last release from her production house 'Ek Villain' became a big financial success. Ekta is known to be always on the lookout for interesting projects but re
Ekta Kapoor snapped at PVR
ekta kapoor News
The hunk with the killer smile, Siddharth Malhotra talked about his upcoming film, 'Ek Villain', his love life and tidbits about his daily life to T2 at Ekta Kapoor's place in Juhu beach. He disclosed that his character in 'Ek villain' is "as black as can be" and he had accepted the role to sho
Looks like producer Ekta Kapoor's next 'Kuku Mathur Ki Jhand Ho Gayi' can get tangled in legal trouble. NL Mathur, a resident of Bhopal has filed a PIL (Public Interest Litigation) in court against Ekta's production company Balaji Motion Pictures claiming the title of the film is offending to Kay


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A 17-year-old boy is dead after being stabbed early Saturday morning when a party in Clovis turned violent. Police say it happened around midnight in the 1300 Block of Reid street.
Upon arriving at the scene, officers found three males suffering from stab wounds. The 17-year-old victim, later identified as Devin Saiz, was stabbed in the torso. He was taken to a local hospital where he later died from his injuries.
The two other young men, 21-year-old Havier Bara and 23-year-old Jose Lopez were also treated for stab wounds, but their wounds were non-life threatening.
Later Saturday evening around 7:00 p.m., officials arrested 27-year-old Ricardo Sena for an Open Count of Murder. Another unidentified female juvenile was also arrested for Aggravated Battery with a Deadly Weapon. Other charges could be filed as the investigation continues.
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Jameson 2 Eco Kids
Black/Green3.5 / 5
This product is out of stock!
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Product Overview
Help reforest Brazil's Atlantic Rainforest by buying the Jameson 2 Eco Kids. The shoe is part of etnies' Buy a Shoe, Plant a Tree reforestation program, which is pretty cool. It's a canvas low-top made with faux-vulc cupsole construction, recycled rubber in the outsole and recycled plastic in the PET shoe laces. It also has a thinly padded tongue and collar for protection and added comfort. Want to plant more than one tree? Check out the entire etnies Buy a Shoe, Plant a Tree kids collection.
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I like colors and the typical Etnies style.
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By Kelly Schremph, Hollywood.com Staff
Money changes everything. Whether you're earning it, spending it, losing it, or in the case of Grey's Anatomy's plane crash victims winning a whopping $15 million in court, any significant change in the moola department can impact your life in a huge way for better or for worse. This week's episode titled "The End Is the Beginning Is the End," made sure to drive this point home with a little trial and error. So grab your scalpels courtroom gavels and let's get this recap started!
McDreamy Returns Sort of: Ever since Derek's surgical hand has been out of commission, so has our beloved McDreamy's storyline. But fortunately, it looks like all of that's about to change. Fresh off his recent nerve surgery, Callie's instructed Derek to play 8 hours of ping-pong with Dr. Williams as a form of physical therapy. And though things got a little overly competitive at one point (though both guys need to work on their trash-talking skills), his hand didn't bother him once, which means our favorite neurological surgeon should be able to scrub back into the OR in no time. Huzzah!
The Ex-Factor: Ironically, Cristina and Owen's divorce is doing wonders for their relationship not to mention their re-established sex life. Yes, they may no longer be husband and wife, but that isn't stopping this on-again, off-again couple from having hot, steamy, on-call sex with one another. So what does this mean? Who knows! But fans can take comfort in knowing that these star-crossed lovers haven't thrown in the towel just yet.
Richard the Remorseful: It's been weeks since Adele's death, but Richard is still suffering from a severely guilty conscience. Not only has he been thwarting Catherine's attempts to comfort him, but he's also flat-out refusing to perform any surgeries. Instead, the ex-Chief has taken to cataloging all the weird Fear Factor-like body parts that he's removed from patients throughout his years as a surgeon (seriously, are hospitals actually allowed to keep all that stuff?!?!). But what were once thought of as (gross) trophies, now serve as bitter reminders of all the times he chose surgery over spending time with his wife. Luckily, Meredith who is bizarrely one of the most normal people on the show now pushes him to get back to the OR and forgive himself for his past wrongdoings. This, naturally, led to some sweet hand-holding between Catherine and a teary-eyed Richard over dinner.
Show Me the Money: And last, but certainly not least, we come to the main event: the lawsuit trial. It's time to decide if the hospital is found guilty and needs to pay the piper or rather the doctors, in this case. The plane crash victims (which include Cristina, Arizona, Meredith, and Derek) were summoned to court where a judge charged Seattle Grace (aka their employer) with negligence and awarded the plaintiffs with a total of $15 million. Each. So they won! They can finally put the ordeal behind them! However, the only one who really feels like celebrating is Callie, who suggests they all go out for a "Survivors Dinner" to commemorate the victory. I get it. It'd be hard to celebrate a win like that when's there's so much that you lost in return (Lexie, Sloan, Arizona's leg). But Callie eventually coaxes all of them into going and manages to put everything into perspective as only she can. "It feels weird and sad and wrong, but it also feels exciting," she said during a toast. "I miss Mark and Lexie and I'm heartbroken that they're not here tonight. But I'm also grateful that all of you are, and I'm going to celebrate that." This seemed to sufficiently lighten the mood and even gave Meredith the courage to officially announce to the group that she's pregnant.
Derek and Cristina call Owen to try and get him to come join in the festivities, but the poor Chief of Surgery is too busy dealing with another huge crisis. During an important meeting with the hospital board, Owen learns that thanks to a loophole in the contract the insurance company is refusing to pay for the lawsuit, forcing the hospital to pay the millions ($60 million to be exact) from its own pocket. The problem is, Seattle Grace doesn't have that kind of cash on hand and will be forced to go bankrupt and close its doors, possibly for good. In other words this could be the end of Seattle Grace.
Other noteworthy items:
-Karev and Wilson are hellbent on keeping things in the friends zone (even though she just bought him furniture for his place, which is a totally girlfriend thing to do).
-Avery admitted to a brokenhearted April that he's currently sleeping with the intern Stephanie. Sorry April, but you only have yourself to blame.
-Bailey learns about vajazzling from an elderly patient (it's hilarious, but also mildly unsettling).
So what did you think of this week's episode? Did you see this big twist coming? Were you surprised by the court's decision? Could this really be the end of Seattle Grace Hospital? Did you know what vajazzling was before now? Sound off on your dissections and opinions in the comments below!
Follow Kelly on Twitter @KellyBean0415
[Photo credit: ABC]
Grey's Anatomy Recap: Bride and Gloom
Grey's Anatomy Recap: Wedding Belle Blues
Grey's Anatomy Recap: We Need to Talk About the Interns
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DANCING WITH THE STARS - This season's dynamic lineup of stars will perform for the first time on live national television with their professional partners during the two-hour season premiere of "Dancing with the Stars," MONDAY, MARCH 18 (8:00-10:01 p.m., ET) on the ABC Television Network. (ABC/Adam Taylor) LINDSAY ARNOLD, SASHA FARBER, GLEB SAVCHENKO
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Grupo Simec, S.A.B. de C.V. announces repurchases of its own shares
GUADALAJARA, Mexico, Oct. 14, 2013 /PRNewswire/ -- Grupo Simec, S.A.B de C.V. (NYSE: SIM) announces to the general public that through its repurchase fund, on October 11, 2013, bought 160,000 of its own shares, (SIMEC-B).
Grupo Simec, S.A.B de C.V. has authorized a repurchase fund of $ 1,000 million pesos, which will be used to support interested investors in generating greater liquidity of its stock in the market, buying stocks when needed and selling them when there is excess of demand.
Grupo Simec and the Group who controls them, reports that they have no interest in selling their shares, as has been the case since the current administration took over, this fund will be operated only to give the necessary support to investors.
The objective of this fund is to increase the turnover of the floating shares, it is not intended to decrease or increase the current number of shares in the market.
Mario Moreno Cortez
SOURCE Grupo Simec, S.A.B. de C.V.
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- Jul 24, 2014, 15:12 ET
- Grupo Simec, S.A.B. de C.V. announces repurchases of its own shares
- Jun 13, 2014, 12:51 ET
- Grupo Simec, S.A.B. de C.V. announces repurchases of its own shares
- Jun 12, 2014, 12:37 ET
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Farm Bureau News BEAVER COUNTY, UTAH Volume 1, BEAVER, UTAH, MAY 1, 1917 Number 2 Street Loafing is a Waste and Crime Against a Country in Need. Loafers Should be Drafted to the Army IT MUST BE DONE NOW "War, except in the interests of righteousness, is a prostitution of all the higher motives of humanity. War for righteousness is the most sublime dedication that mankind can make 1 ecause it involves the giving of the 'last full measure of devotion.' "America is launched upon a war for righteousness. Every resource of the nation will be drawn upon in the prosecution of relentless measures. The farmer particularly will be a soldier of the Republic, because he will supply the one great indispensable— food— without which armies perish and the nation will be defeated." Many of our people could not go to war if they would, many would not if they could, but whatever be our condition in this cause for right- ousness we owe the rendition of our services to the greatest advantage for our country. The boys who have gone to the firing lines to hazard their lives for their country left with full confidence in the support of those they left at home in safety. If we cannot go to the army we must render the next best service. We must produce all the necessary supplies. Every family should strive to raise enough food stuffs to be self- supporting with a surplus for the ones who can't. All promising land should grow crops. Remember, you can't reap unless you sow. For the surplus a non-perishable crop should be grown, such as beans, corn, potatoes, etc. Eat vegetables in season instead of other more expensive things that can he used in winter. Can, preserve and cure all surplus vegetables fruits, eggs and meats. Especially roast and bottle surplus roosters to save feeding them until; wanted to eat. Keep down expenditures for clothing by making over wearing apparel At this time of labor scarcity and need for increased food supplies public sentiment should be so strong against street loafing that everybody will be ashamed to be found in such a condition. City boards should have conspicuous signs printed and erected on prominent loafing corners and places which should read thus: LOAFING IS CRIME AGAINST COUNTRY NEEDS The city police officers should be requested to keep all persons moving on streets, and barber shops and other places should not allow loafing on their premises. and by using the old ones a little longer. Remember, it is not so much the high cost of living as it is the cost of high living. The American people are without doubt the most extravagant people. America is the granary of the world and we must furnish our allies with unstinted amounts of food supplies. The food requirement per capita will be greater this year. We must face the possibility of food destruction in trans-Atlantic shipment. Remember, what is done now will be realized in a few months; what is not done now cannot be corrected to realization for at least one and one-half years from now. USE BEST METHODS Throw away personal notions and be reasonable. Don't bring on a calamity in this time of need by allowing any chances for reduced yields. Be safe by treating all seeds planted against disease. Plant only the best seed obtainable. The difference in price is always compensated for many times over in the yields. Make the best possible seed bed before you plant for you must have a good stand in order to get the biggest yields. MUST SAVE $700,000,000 Dietary specialists of the U. S. Department of Agriculture say $700,- 000,000 worth of good human food is wasted every year in the homes of the United States in the following ways: 1. Edible food thrown into the garbage pail or into the kitchen sink. 2. Spoilage of food due to careless handling and storing in the home. 3. Food spoiled by careless cooking. 4. Waste in preparation. 5. Over-generous serving of food. Let's make the saving of this $700,000,000, rather than spending, our social standard. Let's abandon food prejudices and eat for economy and efficiency. Let's feed our own family first before the hogs. CHILDREN WILL HELP In complinace with the State Executive's call, the county commissions called a meeting of all the county and city leaders, many of whom were present, to take part in planning for Beaver County's part in the struggle. A large share of the county's youth has volunteered and gone to the front. To take their place ir. production the women's organizations and school children are volunteering their services. The County Board of Education are retaining one of their teaching force to supervise club work during tne summer season. The AVilson clubs, Home Economics associations, Relief societies and Young Ladies' Mutual Improvement associations and others are cooperating in arranging for exhibits and canning demonstrations to promote this club work. It is hoped that the public will yield their.part, when asked to do so.
Object Description
|Beaver County Farm Bureau News, 1917-1918;
|Intermitent issues of the Beaver County Farm Bureau News May 1917-September 1918.;
|Date (Display)
|May 1917-September 1918
|Geographic Locations
Beaver County (Utah)
|Time Periods
20th century
Newsletters--Utah--Beaver County
Agriculture, Cooperative--Newspaper
Cooperative societies--Newspaper
|Utah State University, Merrill-Cazier Library, Special Collections and Archives, University Archives 19.21/9 Box 1 Fds 1-15;
|Physical Collection
|University Archives 19.21/9
|Digital Collection
Extension, Enterprise, and Education: the Legacy of Co-operatives and Cooperation in Utah Digital Collection
|Call Number
|Archives 19.21/9 Box 1 Fds 1-15
|Date Digital
|Digital Publisher
|Digitized by : Utah State University, Merrill-Cazier Library;
|Reproduction for publication, exhibition, web display or commercial use is only permissible with the consent of the USU Libraries USU Archives curator, phone (435) 797-0894.;
|Contributing Institution
|Utah State University, Merrill-Cazier Library;
|Conversion Specifications
|Scanned by Utah State University, Merrill-Cazier Library using Epson Expression 10000 scanner, 8-bit RGB, at 400 dpi. Archival file is uncompressed TIFF (400 dpi); display file is JPEG2000.;
|Date (Original)
|1917; 1918
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The following arrests were made by Minden Police the week of March 11 through March 17
March 11
Monica Robertson, 33, of Arcadia, was arrested for felony possession of CDS Sch. I marijuana and a Probation and Parole violation.
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