NEJM -- The Path to Personalized Medicine (U.S.)

"...In February, the NIH and the FDA announced a new collaboration on regulatory and translational science to accelerate the translation of research into medical products and therapies; this effort includes a joint funding opportunity for regulatory science. Working with academic experts, companies, doctors, patients, and the public, we intend to help make personalized medicine a reality. A recent example of this collaboration is an effort to identify new investigational agents to which certain tumors, identified by their genetic signatures, are responsive.
Real progress will come when clinically beneficial new products and approaches are incorporated into clinical practice. As the field advances, we expect to see more efficient clinical trials based on a more thorough understanding of the genetic basis of disease. We also anticipate that some previously failed medications will be recognized as safe and effective and will be approved for subgroups of patients with specific genetic markers.


When the federal government created the national highway system, it did not tell people where to drive — it built the roads and set the standards for safety. Those investments supported a revolution in transportation, commerce, and personal mobility. We are now building a national highway system for personalized medicine, with substantial investments in infrastructure and standards. We look forward to doctors' and patients' navigating these roads to better outcomes and better health."

ASCO: Continuity of care for cancer patients at the end of life (EoL). -- Bascioni et al. 28 (15): 6145 -- ASCO Meeting Abstracts

Conclusion: Continuity of care at the EoL is a priority issue for the families of cancer pts. The daily routine of palliative care and hospice facilities should involve the oncologist to improve the experience of care. Patients' families expect a commitment by the oncologist in bereavement activities.

Gene Expression Profile of BRCAness That Correlates With Responsiveness to Chemotherapy and With Outcome in Patients With Epithelial Ovarian Cancer -- Konstantinopoulos et al., 10.1200/JCO.2009.27.5719 -- Journal of Clinical Oncology

Commentary: June 14th: Personalizing Therapy for Ovarian Cancer: BRCAness and Beyond -- Bast and Mills, 10.1200/JCO.2010.28.5791 -- Journal of Clinical Oncology

Note: links directly to pdf article/overview of ovarian cancer treatments including PARPs, Avastin, Tamoxifen, AZ6244..

"If we are to progress at an optimal pace, accrual of a larger fraction of patients to clinical trials will be essential, requiring referral of ovarian cancer patients to major centers at first recurrence of their disease."

Merger of Cancer Australia and NBOCC will unify efforts to address increasing cancer rates

15 June 2010

"The Australian Government’s planned amalgamation of Cancer Australia and the National Breast and Ovarian Cancer Centre (NBOCC) should consolidate efforts to address the nation’s escalating cancer incidence rates, Cancer Council Australia and the Clinical Oncological Society of Australia (COSA) said today (15 June)...."

Trials to detect early ovarian cancer - The West Australian (media report)

Society of Gynecologic Oncologists Statement on Use of CA125 in Screening for Ovarian Cancer

press release:
June, 2010
Society of Gynecologic Oncologists Statement on Use of CA125 in Screening for Ovarian Cancer

Results of a multicenter screening trial using calculated algorithms based on age and trends in CA125 levels over time in women without familial risk of developing ovarian cancer have recently been reported at the annual meeting of the American Society of Clinical Oncology. Transvaginal ultrasound (TVUS) was not performed automatically but as indicated by the CA125 algorithm results. This study provides early evidence that incorporating a CA125 algorithm followed by TVUS may be a feasible strategy for screening low-risk women over 50 years of age. The results of this study have been featured in various professional and consumer media outlets, causing physicians and patients to seek guidance regarding the implications.

The Society of Gynecologic Oncologists commends the investigators of this study for contributing valuable data, and eagerly awaits the results of additional larger randomized controlled trials to confirm the usefulness of Risk of Ovarian Cancer Algorithm (ROCA) in screening women without familial risk of ovarian cancer. The positive predictive value noted in the study of 37.5% is superior to what has been reported from prior studies. However, as a screening strategy, that eventually could be applied to the general population, this figure is modest. There remains insufficient evidence to support routine CA125 +/- TVUS screening in low-risk women who are not part of a clinical trial. An additional limitation of this study was the lack of a control, observation-only arm, without which it is difficult to attribute any real benefit to the screening strategy. As with any prospective screening tool or treatment option, the impact of false positive and false negative screening results must be considered and balanced against the potential benefits of true positive and negative results. Finally, while the number of participants who needed more frequent CA125 monitoring, ultrasound, or referral to a specialist appeared small, a complete cost effectiveness analysis of this approach would be critical before adopting any universal screening program.

As specialists in women’s cancer care, gynecologic oncologists offer patients individualized treatment plans. Patients and their physicians are encouraged to discuss the pros and cons of CA125 and TVUS screening and the implications for subsequent treatment and quality of life.

Breakthrough Pain Significant for Many Cancer Patients

Note: this is a good article/registration required (free)

MuGard (oral mucositis - U.S.) Access Pharma Initiates US MuGard Sampling Program with Leading Oncology Groups - MarketWatch

"...Sampling efforts for the company include providing large oncology groups with MuGard kits containing six weeks' worth of MuGard therapy for patients undergoing radiation and chemotherapy. Through these oncology groups, Access Pharma initially will provide 500 patients throughout 20 top metropolitan areas full courses of therapy to protect them from oral mucositis."

p53 autoantibodies as potential detection and prognostic biomarkers in serous ovarian cancer

IMPACT: Although their utility as a preoperative diagnostic biomarker, beyond CA 125 and HE4, is limited, p53-AAb are prognostic for improved overall survival.

Hospice enrollment for terminally ill patients with gynecologic malignancies: Impact on outcomes and interventions

CONCLUSIONS: While retrospective reviews evaluating hospice are challenging, our data suggest no detrimental impact on survival for hospice patients (vs non hospice). Continued evaluation for patients at the end-of-life is necessary in order to optimize resource utilization.

Neurobiological cause of intergroup conflict: 'Bonding hormone' drives aggression towards competing out-groups (altruism)

"The evolution of altruism in intergroup conflict
The research team at the University of Amsterdam, directed by Dr. Carsten de Dreu, wondered why oxytocin would promote altruistic behavior. Whereas classic economic theory has difficulty accounting for altruism, an evolutionary perspective suggests that altruism functions to strengthen one's own group, from which the individual benefits in the long run. Because aggression towards competing out-groups helps one's own group to become relatively stronger, aggression is an indirect form of altruistic, loyal behavior towards one's own group........Charles Darwin already observed that groups whose members are altruistic towards the own group have a greater likelihood to prosper, to survive, and spread...."

First-in-human trial of a poly(ADP-ribose) polymerase (PARP) inhibitor MK-4827 in advanced cancer patients (pts) with antitumor activity in BRCA-deficient and sporadic ovarian cancers (phase 1)

Results: 39 pts (male 10, female 29; median age 58 years; 11 BRCA mutation carriers) were treated...
Conclusions: MK-4827 is well tolerated, blocks PARP and has promising antitumor activity in both BRCA-deficient and sporadic cancers.

Efficacy of lower dose of weekly topotecan in recurrent epithelial ovarian and primary peritoneal cancer resistant to platinum-based therapy

Conclusions: Lower dose of weekly topotecan was well tolerated in patients with platinum-resistant ovarian or peritoneal cancer at first relapse, with a favourable hematologic profile. Moreover, antitumor activity was similar to that reported for the standard dose of weekly regimen.

Associations between age and quality of life in advanced ovarian cancer

Background:
..... Few studies have examined whether age influences advanced ovarian cancer patients' prognostic understanding or quality of life at the time of diagnosis."

Conclusions: EpCAM is highly expressed in primary chemotherapy- resistant ovarian carcinoma cell lines, and these chemotherapy-resistant tumors are highly sensitive to MT201-mediated cytotoxicity in vitro. MT201 may represent a novel, potentially highly effective treatment option for patients harboring chemotherapy-resistant ovarian carcinoma.

Note: EpCAM epithelial cell adhesion molecule (EpCAM); EpCAM gene can be tested either independently or as part of genetic testing - depending on the testing procedure (eg. Lynch Syndrome); study included clear cell ovarian cancer

(Review) Methodologic challenges in assessing patient-reported outcomes among women with relapsed/refractory ovarian cancer - QOL

Note: study of mechanisms in identifying QOL

Conclusions: PRO among women with R/R ( relapsed/refractory)ovarian cancer is limited in quality. More data are needed from R/R ovarian cancer studies to identify not only the most appropriate PRO instruments, but also methodologic strategies necessary to yield useful PRO data

Interleukin-6 as a therapeutic target in advanced ovarian cancer

Note: "Four of the eighteen patients completed 6 months of treatment and this included the partial responder who had continued decreases..."

Nonepithelial ovarian cancer: Outcomes after aggressive treatment with surgery and platinum-based chemotherapy

Conclusions:
In this high-recurrence-risk group of nonepithelial ovarian cancers, aggressive treatment with surgery and platinum- based chemotherapy resulted in excellent survival outcomes.

A KRAS-variant as a biomarker of ovarian cancer risk

Note: KRAS has been studied in colorectal cancer impacting on treatment program/no indication if ovarian cancer/Lynch Syndrome patients were included

Conclusions: These findings strongly support the hypothesis that the KRAS-variant is a genetic marker of an increased risk of developing ovarian cancer, and suggests that the KRAS- variant may be a new biomarker of risk for HBOC families without other known genetic abnormalities. In addition, the KRAS-variant predicts for the most deadly ovarian cancers, which are likely the most important to prevent or catch early.

abstract: A prospective U.S. ovarian cancer screening study using the risk of ovarian cancer algorithm (ROCA)

ASCO (Post-Meeting Edition)
Abstract
5003
Background: There are currently no effective screening tools for the early detection of ovarian cancer in women at average population risk. We evaluated a screening strategy that incorporates change of CA-125 over time and age of the participant to estimate risk of ovarian cancer, referring a small fraction (2%) of apparently healthy individuals annually to transvaginal sonography (TVS).
Methods: A single arm, prospective, multicenter screening study enrolled postmenopausal women age 50 to 74 with no significant family history of breast or ovarian cancer. Participants underwent a CA-125 blood test annually. Based on the Risk of Ovarian Cancer Algorithm (ROCA) result, women were triaged to the next annual CA-125 (low risk), repeat CA-125 in 3 months (intermediate risk), or TVS and referral to a gynecologic oncologist (high risk). Based on clinical findings and TVS, the gyn onc made the decision whether to proceed with surgery.
Results: 3238 women participated over an eight year period. The average annual rate of referral to 3 monthly CA125 was 6.8%, and the average annual rate of TVS and gyn onc referral was 0.9%. Cumulatively 85 women (2.6%) received TVS and referral to a gyn onc. Eight women subsequently underwent surgery based on the TVS and referral, with 3 invasive ovarian cancers, 2 borderline ovarian tumors and 3 benign ovarian tumors, providing a positive predictive value of 37.5% (95% CI 8.5%,75.5%).The combined specificity of ROCA followed by TVS for referral to surgery is 99.7% (95% CI 99.5%, 99.9%). The 3 invasive ovarian cancers were high-grade epithelial tumors that were all early stage (two stage 1C and stage IIB). All 3 women with invasive ovarian cancer had at least 3 years with low risk, annual CA-125 values prior to a rising CA-125.
Conclusions: In this prospective, single arm study, the ROCA followed by TVS demonstrated excellent specificity and PPV in a population of U.S. women at average risk for ovarian cancer. As expected, less than 1% of participants annually required a TVS. In addition, the invasive high-grade ovarian cancers that were detected were early stage. This study provides early evidence that ROCA followed by TVS is a feasible strategy for screening women over 50 years of age.