Friday, February 12, 2016
SATB2 Expression Distinguishes Ovarian Metastases of Colorectal and Appendiceal Origin From Primary Ovarian Tumors of Mucinous or Endometrioid Type
The primary origin of some ovarian mucinous tumors may be challenging to determine, because some metastases of extraovarian origin may exhibit gross, microscopic, and immunohistochemical features that are shared by some primary ovarian mucinous tumors. Metastases of primary colorectal, appendiceal, gastric, pancreatic, and endocervical adenocarcinomas may simulate primary ovarian mucinous cystadenoma, mucinous borderline tumor, or mucinous adenocarcinoma. Recently, immunohistochemical expression of SATB2, a transcriptional regulator involved in osteoblastic and neuronal differentiation, has been shown to be a highly sensitive marker of normal colorectal epithelium and of colorectal adenocarcinoma. SATB2 expression has not been reported in normal epithelium of the female reproductive tract. Therefore, we hypothesized that SATB2 may be of value in distinguishing ovarian metastases of colorectal adenocarcinoma from primary ovarian mucinous tumors and from primary ovarian endometrioid tumors.
Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes
Invasion Patterns of Metastatic Extrauterine High-grade Serous Carcinoma With BRCA Germline Mutation and Correlation With Clinical Outcomes
Characteristic histopathologic features have been described in high-grade serous carcinoma associated with BRCA abnormalities (HGSC-BRCA), which are known to have relatively favorable clinical outcomes. The aim of this study was to evaluate the clinical significance of invasion patterns in metastatic HGSC-BRCA cases. Of the 37 cases of advanced-stage HGSC with known BRCA1 or BRCA2 germline mutation retrieved from our institutional files, 23 patients had a germline mutation of BRCA1 and 14 had a BRCA2 mutation. The pattern of invasion at metastatic sites was recorded and classified as a pushing pattern (either predominantly or exclusively), an exclusively micropapillary infiltrative pattern, or an infiltrative pattern composed of papillae, micropapillae, glands, and nests (mixed infiltrative pattern). Histologic evaluation of metastases was performed without knowledge of genotype or clinical outcome. Clinical data were abstracted from medical records. Median age was 56 years (range, 31 to 73 y).
Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type
Loss of SMARCA4 Expression Is Both Sensitive and Specific for the Diagnosis of Small Cell Carcinoma of Ovary, Hypercalcemic Type
Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare ovarian neoplasm that occurs in young women
Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma...
Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors
Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell–like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.
Extreme ﬁnancial distress appeared to inﬂuence survival after cancer diagnosis and may be taking a greater toll on patients than previously recognized, Seattle researchers have found.1.....
“Oncologists need to be mindful that their patients may have a tenuous financial situation that could prevent them from completing planned therapies,” said study investigator Scott Ramsey, MD, PhD, director of the Hutchinson Institute for Cancer Outcomes Research at the Fred Hutchinson Cancer Center in Seattle, WA, in an interview with Cancer Therapy Advisor.
Vinay Prasad, MD, MPH, assistant professor of medicine at the Oregon Health & Science University Knight Cancer Institute in Portland, said this is becoming a greater concern than ever before.
“We are already thinking about biological toxicity, and now we have to think about a whole new class of toxicity. We have to deal with these toxicities and no longer ignore them,” Dr Prasad told Cancer Therapy Advisor.
Editorial: The Lancet Oncology
This year's JP Morgan Annual Healthcare Conference (Jan 11–15, 2016) in San Francisco, CA, USA, saw the announcement of a new biotechnology company called Grail—a spinoff from Illumina (San Diego, CA, USA; one of the world's largest diagnostics companies). Chaired by the Illumina Chief Executive Officer Jay Flatley, and with a science advisory board headed by José Baselga (Memorial Sloan Kettering Cancer Center, New York, NY, USA), Grail declared its mission to be “the early detection of cancer in asymptomatic individuals through a blood screen”. Flatley's aim is to deliver this ambitious pan-tumour test in just 3 years. The notion of cancer detection by liquid biopsy is not a new concept: indeed, many other companies are also developing blood-based tests to monitor cancer progression or screen high-risk asymptomatic individuals. However, such tests to date have focused on specific cancer types, rather than a single test to detect all aysmptomatic cancers based on circulating tumour DNA (ctDNA). Is this objective possible? And what are the wider implications for patients with cancer?....
Grail's endeavour, however, is laudable in its ambitious scope, and it will be fascinating to watch over the coming years whether the company achieves its objective.
JAMA Oncology (Narod)
Differing Perspectives on Breast Cancer Chemoprevention
Jack Cuzick, PhD; Larry Wickerham, MD; Trevor Powles, MD
Differing Perspectives on Breast Cancer Chemoprevention
V. Craig Jordan, OBE, PhD, DSc, FMedSci
Clarifying Assumptions and Outcomes in Cost-effectiveness Analyses
Kevin ten Haaf, MSc; Harry J. de Koning, MD, PhD
Differing Perspectives on Breast Cancer Chemoprevention—Reply
Steven A. Narod, MD
Clarifying Assumptions and Outcomes in Cost-Effectiveness Analyses—Reply
John R. Goffin, MD, FRCPC; William M. Flanagan, BM; William K. Evans, MD, FRCPC
JAMA (full access requires $$)
Advances in cancer therapy have led to increased survival; there are more than 9 million 5-year survivors of cancer in the United States.1 As this number continues to grow, focus on improved health and quality of life becomes a priority. It is especially important in survivors of childhood, adolescent, and young adult cancer who have 5-year survival rates exceeding 80%1 and who are expected to live many decades after diagnosis and treatment. Because of their young age at treatment, this population is the most vulnerable to long-term detrimental effects of cancer therapy. Many studies have shown that childhood and adolescent cancer survivors are at increased risk for chronic medical problems and emotional late effects as they age.2- 5 These late effects influence overall health and quality of life.
JAMA: Incomplete Conflict of Interest Disclosure (Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: The ABOUT Study)
Incomplete Conflict of Interest Disclosure
In the Original Investigation titled “Utilization and Outcomes of BRCA Genetic Testing and Counseling in a National Commercially Insured Population: The ABOUT Study,”1 published in the December 2015 issue of JAMA Oncology, the conflict of interest disclosure statement in the Article Information section was incomplete. The original statement was “Dr Sutphen has received personal fees from InformedDNA outside the present work. No other disclosures are reported.” This should have been “Dr Sutphen received payment for serving as President and Chief Medical Officer of InformedDNA, which provides a network of genetics specialists and a library of genetic tests and hereditary conditions. No other disclosures are reported.” The article has been corrected online.
In contrast, somatic mosaic mutations in TP53 were not significantly associated with chemotherapy or age.
Conclusions and Relevance Chemotherapy exposure and age influence the accumulation of PPM1D-mutated PBMC (peripheral blood mononuclear cells) clones. Care should be taken to control for chemotherapy exposure and age at blood draw when testing the association of somatic mosaic mutations in PBMCs with cancer risk.
Increased Reach of Genetic Cancer Risk Assessment as a Tool for Precision Management of Hereditary Breast Cancer
JAMA Network - Editorial (open access)
It is disconcerting that 48% of those who did not get testing indicated that they and/or their physician did not think a BRCA mutation was likely, despite the fact that the National Comprehensive Cancer Network (NCCN) guideline2 has recommended genetic counseling and BRCA testing for women with breast cancer diagnosed at 40 years or younger since the outset of the YWS study.
Thursday, February 11, 2016
Blogger's Note: new website/venture (aka. at your own risk)
The HEROIC Registry, Hereditary Cancer Research Champions
HEROIC Registry - Hereditary Cancer Research Champions
SHARE... Answer as many questions as you would like, and control how and with whom that information is shared. CONNECT... Find out how you compare to others, and let support and helpful resources come to you. DISCOVER... If you wish, let researchers access your information to help spark innovation for all. Simply click on Start Now! to begin, or Sign In if you are a returning user....
GI news: Lynch Syndrome patient registry
AliveAndKickn has announced the launch of the HEROIC Registry, a genetic database for people with Lynch Syndrome to share data and further research, according to a press release.
“If other Lynch patients are like me they will want their data shared with researchers to get a better understanding of how to manage their condition and get involved with research studies and clinical trials,” David Dubin, founder of AliveAndKickn and three-time Lynch cancer survivor, said in the press release. “This registry will enable me as a patient to truly make a difference in the research of this condition.”The registry will enable researchers to utilize patient data in their efforts to better understand the mutations, perform clinical trials and develop new treatments, according to the press release. Patients will have control over what data are provided.
The Challenge of Turning Negative Patient Experiences Into Positive Learning Opportunitiesprint version (text all on one page)
ConclusionIt seems evident that before educators broadly engage patients and families in patient safety training, they will need to: (1) know more about the link between the affective impact of patient narratives and long-term learner outcomes; and (2) develop strategies to mitigate potential negative emotional and cognitive impacts on the learner and the patient or family. One suggestion would be to borrow from more well-established educational approaches, such as the use of high-fidelity simulation and SPs, to inform the patient training and faculty development requirements needed to maximise learning outcomes. Understanding exactly how these elements factor into the planning and delivery of patient safety education that involves patient narratives needs further attention, and will rely on a broad range of study methodologies that extend beyond traditional experimental designs. Future research must also focus on better understanding and mitigating the potential harms that patients experience as trainers. Only then can we be confident that we are optimising the use of patient narratives to deliver the best possible patient safety training to our learners.
JAMA Network - open access
Viewpoint | February 11, 20161Division of Medical Ethics, NYU Langone Medical Center, New York, New York
2Janssen Research & Development LLC, Titusville, New Jersey
Requests for rapid access to agents still under investigation fall into 2 categories—requests for groups of persons with the same disease and requests by individuals. The former are often described as requests for expanded access, the latter as requests for compassionate use. Regulatory bodies in various countries have created various programs for providing greater access to requests from groups, including the creation of expanded-access programs and emergency use waivers for patients who do not qualify for clinical trials. Compassionate use requests have proven to be more difficult to resolve.
Comparison of cancer survival trends (U.S.) of adolescents & young adults with those in children & older adults
With prior reports indicating a lack of progress in survival improvement in older adolescents and young adults (AYAs) aged 15 to 39 years with cancer compared with both younger and older patients with cancer, the current analysis provides an update of survival trends of cancers among AYAs, children, and older adults.
Data from the National Cancer Institute Surveillance, Epidemiology, and End Results database for 13 regions were used to ascertain survival trends of the 34 most frequent cancers diagnosed in AYAs compared with children and older adults.
As of 2002 through 2006, the 5-year relative survival rate for all invasive cancers in AYAs was 82.5% (standard error, 0.2%). In AYAs, 14 cancers demonstrated evidence of a statistically significant improvement in their 5-year relative survival since 1992. Survival improved less in AYAs than in children for acute myeloid leukemia and medulloblastoma. Fourteen cancers had survival improvements that were found to be less in AYAs compared with older adults, including hepatic carcinoma, acute myeloid leukemia, high-grade astrocytoma, acute lymphocytic leukemia, pancreatic carcinoma, low-grade astrocytoma, gastric carcinoma, renal carcinoma, cancer of the oral cavity and pharynx, Hodgkin lymphoma, ovarian cancer, fibromatous sarcoma, other soft tissue sarcoma, and thyroid carcinoma.
CONCLUSIONSImprovements in the survival of several cancer types that occur frequently in AYAs are encouraging. However, survival does not appear to be improving to the same extent in AYAs as in children or older adults for several cancers. Further investment in exploring the distinct biology of tumors in this age group, and of their hosts, must be a priority in AYA oncology.
Ototoxicity is a well-established toxicity associated with a subgroup of antineoplastic therapies that includes platinum chemotherapy, radiation or surgery involving the ear and auditory nerve, and supportive care agents such as aminoglycoside antibiotics and loop diuretics. The reported prevalence of ototoxicity in patients who have received potentially ototoxic therapy ranges from 4% to 90% depending on factors such as age of the patient population, agent(s) used, cumulative dose, and administration techniques. The impact of ototoxicity on subsequent health-related and psychosocial outcomes in these patients can be substantial, and the burden of morbidity related to ototoxic agents is particularly high in very young children. Considerable interindividual variability in the prevalence and severity of ototoxicity has been observed among patients receiving similar treatment, suggesting genetic susceptibility as a risk factor. The development and testing of otoprotective agents is ongoing; however, to the author's knowledge, no US Food and Drug Administration-approved otoprotectants are currently available. Prospective monitoring for ototoxicity allows for comparison of auditory outcomes across clinical trials, as well as for early detection, potential alterations in therapy, and auditory intervention and rehabilitation to ameliorate the adverse consequences of hearing loss.
The use of real-world evidence is critical to transforming health care, and policies need to address this issue. Although the availability of multiple standards/guidelines has the potential to improve the quality and credibility of observational studies, there may be unintended consequences. If those guidelines differ from one another, decisions based on one guideline may subsequently be found deficient if measured against a different one.
- Nine major standards/guidelines for observational studies have areas of disagreement based on a comparison of 23 common elements.
What this adds to what was known?
- Comparison of the standards/guidelines is presented, along with an assessment of how actionable each is, and a policy discussion of next steps is provided.
What is the implication and what should change now?
- Lack of standard/guideline agreement may contribute to variation in study conduct.
- Common standards/guidelines for conducting observational studies will benefit funders, researchers, journal editors, and decision makers.
- A consensus process to determine a common set of standards/guidelines needs to be established.The nine standards/guidelines are as follows: Agency for Healthcare Research Quality (AHRQ): Developing a Protocol for Observational Comparative Effectiveness Research ; Comparative Effectiveness Research Collaborative: Observational Study Assessment Questionnaire ; European Network of Centres for Pharmacoepidemiology and Pharmacovigilance (ENCePP) Checklist for Study Protocols ; ENCePP Guide on Methodological Standards in Pharmacoepidemiology ; The United States Food and Drug Administration (FDA): Guidance for Industry Good Pharmacovigilance Practices and Pharmacoepidemiologic Assessment ; Good ReseArch for Comparative Effectiveness (GRACE) Checklist ; GRACE Principles ; ISPOR Good Research Practices for Retrospective Database Analysis Task Force Report (Parts I, II, and III combined) ,  and ; and Patient-Centered Outcomes Research Institute (PCORI) Methodology Standards .
open access (pdf)
The diagnosis of Lynch syndrome is essential since the patient has a high risk for developing many other cancers and needs appropriate surveillance.
"Descriptions of the identity of these genes and their frequency was lacking in the medical literature," Dr. DiSilvestro explains. "The goal of this research was to better define these issues."
More than 1,900 women with ovarian cancer who were identified through the University of Washington gynecologic tissue bank and from various GOG clinical trials made up the study population.
What the evaluations revealed was that 18 percent of the women with ovarian cancer carried mutations in genes associated with ovarian cancer risk beyond the BRCA1 and BRCA2 genes.Journal Reference:
- Inherited Mutations in Women With Ovarian Carcinoma. JAMA Oncology, 2015; 1 DOI: 10.1001/jamaoncol.2015.5495
Conclusions and Relevance Of 1915 patients with OC, 347 (18%) carried pathogenic germline mutations in genes associated with OC risk. PALB2 and BARD1 are suspected OC genes and together with established OC genes (BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, and MSH6) bring the total number of genes suspected to cause hereditary OC to 11.
Running Time: (4:26)
Wednesday, February 10, 2016
Blogger's note: for the many ovarian cancer survivors and their love of horses
Clear cell carcinoma arising in previous episiotomy scar: a case report and review of the literature
Malignant transformation of endometriosis associated with episiotomy scar is a rare event, especially histological type of clear cell adenocarcinoma. There are only three clear cell carcinoma in episiotomy scar reported, no standard treatment established.
We report a case of clear cell carcinoma arising from episiotomy scar. There are only three clear cell carcinoma in episiotomy scar reported, no standard treatment established. Accumulation of management data on these rare tumors and long-term follow-up of such patients is therefore important.
A 36-year-old woman presented with a two-month history of painless but puritic perineal lump which she noticed was gradually enlarging. The patient’s past gynecological history included frequent vaginitis owing to bad health habits and the lack of professional treatment. Because of discomfort, the patient often scratched the vulva including the lesion of the episiotomy scar for many years. In addition, her past obstetric history was significant. She had a history of a forceps delivery 20 years ago. The postoperative recovery of perineal wound was slow. Several months after delivery, she experienced cyclic perineal pain and swelling of the episiotomy scar. Mifesterone and Medroxyprogesterone acetate injectable suspension (DMPA) were used and the pain was relieved. She had undergone surgical excision of a mass in the episiotomy scar 9 year ago and resequently histological type of endometriosis. DMPA was administrated for one year and then mifesterone for half a year. Medical treatment with Chinese traditional medicine was prescribed after that.....
BACKGROUND:We present the results of the TGM-95 study for gonadal sex-cord stromal tumors (SCT).
METHODS:Between 1995 and 2005, children (<18 years) with gonadal SCT were prospectively registered. Primary gonadal resection was recommended whenever feasible. Patients with disseminated disease or an incomplete resection received neoadjuvant or adjuvant VIP chemotherapy (etoposide, ifosfamide, cisplatinum).
RESULTS:Thirty-eight children with ovarian SCT were registered. Median age was 10.7y. Endocrine symptoms were present in 21 cases. The histological diagnoses were as follows: juvenile (23) and adult (3) granulosa cell tumors, Sertoli-Leydig cell tumors (11), and mixed germ cell SCT (1). An initial oophorectomy ± salpingectomy led to complete resection in 23 patients who did not receive adjuvant treatment; two of them relapsed: one achieved second complete remission whereas the other one died of disease. Fifteen patients had tumor rupture and/or malignant ascites: 11 received chemotherapy and did not relapse, four did not receive chemotherapy and relapsed with a fatal outcome in two cases. With a median follow-up of 5.9y, the 5-y EFS and OS rates were respectively 85% and 94%. Eleven patients had localized testicular tumors (median age 0.83y): juvenile granulosa cell tumors (4), Sertoli or Leydig cell tumors (5) and not otherwise specified SCT (2). Treatment was surgery alone with an inguinal orchiectomy. None have relapsed (median follow-up: 5.4y).
CONCLUSIONS:Childhood SCT carry favorable prognosis. In ovarian SCT, surgery should be complete and non-mutilating. Adjuvant chemotherapy efficiently prevents recurrences in cases of tumor rupture. In childhood testicular SCT, the prognosis is excellent with an inguinal orchiectomy, prompting the debate on testis-sparing surgery.
Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2
Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2 | Breast Cancer Research | Full Text
The lifetime risk of developing MBC has been estimated to be in the range of 1–5 % for BRCA1 and 5–10 % for BRCA2 mutation carriers, compared with a risk of 0.1 % in the general population [6–9].
On the basis of the largest series analysed to date, our results show that BRCA1/2 MBCs display distinct pathologic characteristics compared with BRCA1/2 FBCs (female), and we identified a specific BRCA2-associated MBC phenotype characterised by a variable suggesting greater biological aggressiveness (i.e., high histologic grade). These findings could lead to the development of gender-specific risk prediction models and guide clinical strategies appropriate for MBC management.
Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports
open access: Etiology of Ascites and Pleural Effusion Associated with Ovarian Tumors: Literature Review and Case Reports of Three Ovarian Tumors Presenting with Massive Ascites, but without Peritoneal Dissemination
BACKGROUND:Patient navigation (PN) is a patient-centered health-care service delivery model that assists individuals, particularly the medically underserved, in overcoming barriers (e.g., personal, logistical, and system) to care across the cancer care continuum. In 2012, the American College of Surgeons Commission on Cancer (CoC) announced that health-care facilities seeking CoC-accreditation must have PN processes in place starting January 1, 2015. The CoC mandate, in light of the recent findings from centers within the Patient Navigation Research Program and the influx of PN interventions, warrants the present literature review.
METHODS:PubMed and Medline were searched for studies published from January 2010 to October 2015, particularly those recent articles within the past 2 years, addressing PN for breast and gynecological cancers, and written in English. Search terms included patient navigation, navigation, navigator, cancer screening, clinical trials, cancer patient, cancer survivor, breast cancer, gynecological cancer, ovarian cancer, uterine cancer, vaginal cancer, and vulvar cancer.
RESULTS:Consistent with prior reviews, PN was shown to be effective in helping women who receive cancer screenings, receive more timely diagnostic resolution after a breast and cervical cancer screening abnormality, initiate treatment sooner, receive proper treatment, and improve quality of life after cancer diagnosis. However, several limitations were observed. The majority of PN interventions focused on cancer screening and diagnostic resolution for breast cancer. As observed in prior reviews, methodological rigor (e.g., randomized controlled trial design) was lacking.
CONCLUSION:Future research opportunities include testing PN interventions in the post-treatment settings and among gynecological cancer patient populations, age-related barriers to effective PN, and collaborative efforts between community health workers and patient navigators as care goes across segments of the cancer control continuum. As PN programs continue to develop and become a standard of care, further research will be required to determine the effectiveness of cancer PN across the cancer care continuum, and in different patient populations.
Predicting Low Accrual in the National Cancer Institute’s Cooperative Group Clinical Trials
JNCI J Natl Cancer Inst (2016) 108 (2): djv324 doi:10.1093/jnci/djv324 First published online December 29, 2015 (7 pages)
Tuesday, February 09, 2016
Dr. Lucy Gilbert, chief of the MUHC’s gynecologic-oncology division and one of the signatories of the letter, said that under the proposal, the Women’s Health Mission would likely be split between the departments of pediatrics and surgery in the hope of saving up to $12 million a year.
So who is actually articulating these superlatives?
Mostly, it is journalists (55% of all the superlatives used, with no other attribution). Then, in order of frequency, it is physicians (27%), industry experts (9%), patients (8%), and a member of the US Congress (1%).
Clinical Oncology News
Yet, quite remarkably, despite extensively reported and validated data regarding objectively impressive improvements in both the quality and quantity of life for individuals diagnosed with advanced or metastatic cancers, these facts do not appear to have reached the consciousness of the entire medical establishment.
Clinical Oncology News (requires login to view - free)
Although Lynch syndrome is almost as prevalent as hereditary breast and ovarian cancer (HBOC), twice as many patients are undergoing testing for breast and ovarian cancer as for GI cancer syndromes, according to a recent study presented at the 2015 annual meeting of the American College of Gastroenterology (abstract P159)......
Observing that there were few referrals for GI cancers during the interim analysis of this study, the researchers set out to quantify the extent of the problem. In an analysis of 500 patients, almost twice as many patients received genetic testing for a primary workup of HBOC as for a workup of GI cancer syndromes (66.4% vs. 28.8%). Although newly diagnosed colorectal and gastric cancer constituted 42% of the approximately 1,798 new diagnoses of all breast, ovarian, colorectal and GI cancers at the three centers, only 29% of the tests were ordered for GI indications.
ecancer - News
A novel Yale study answers age-old questions about how cancers spread by applying tools from evolutionary biology.
The new insights will help scientists better understand the genetic origins of tumour metastases, and lead to more effective targets for treatment, said the researchers.
The study, led by associate professor of public health (biostatistics) Jeffrey Townsend, was published by the Proceedings of the National Academy of Sciences.
Scientists have long thought that cancer is an evolutionary process that involves cells acquiring mutations that replicate and persist over time, gaining an advantage over normal cells.
But questions remained about the timing and course of tumour progression.....
Background: Hormonal and reproductive factors contribute to the development of ovarian cancer, but few studies have examined associations between circulating estrogens and estrogen metabolites and ovarian cancer risk. We evaluated whether serum estrogens and estrogen metabolite levels are associated with ovarian cancer risk among postmenopausal women in a nested case-control study in the Women's Health Initiative (WHI) Observational Study (OS).
Editorial: Making a Difference: Distinguishing 2 Primaries From Metastasis in Synchronous Tumors of the Ovary/Uterus
For women with early-stage ovarian or endometrial cancers, prognosis is very good, with overall survival for both sites between 80% and 90%. This stands in stark contrast to metastatic disease (advanced stage), where the overall survival is less than 15%. We have long recognized that subtypes of disease also inform these statistics, with high-grade serous carcinomas conferring a far worse prognosis compared with others, including low-grade serous or endometrioid tumors. Yet even with our present understanding, a not uncommon finding is the diagnosis of women with carcinoma at both the ovary and the uterus (a situation that occurs in up to 10% of patients), raising the question of synchronous primaries or of metastatic disease. The implications of these clinical senarios are very relevant: If a conclusion of synchronous primaries is made, then prognosis should be excellent and hence no further treatment beyond surgery is required for cure. However, the finding of metastatic disease (from the ovary to the uterus or vice versa) will substantially change the prognostic implications, with these patients having a higher risk of recurrence and death from metastatic disease. In addition, this differential diagnosis can change therapeutic recommendations, with metastatic disease requiring more aggressive adjuvant therapy. Thus, the issue is both a biologic and clinical one.
Massively Parallel Sequencing-Based Clonality Analysis of Synchronous Endometrioid Endometrial and Ovarian Carcinomas
Synchronous early-stage endometrioid endometrial carcinomas (EECs) and endometrioid ovarian carcinomas (EOCs) are associated with a favorable prognosis and have been suggested to represent independent primary tumors rather than metastatic disease. We subjected sporadic synchronous EECs/EOCs from five patients to whole-exome massively parallel sequencing, which revealed that the EEC and EOC of each case displayed strikingly similar repertoires of somatic mutations and gene copy number alterations. Despite the presence of mutations restricted to the EEC or EOC in each case, we observed that the mutational processes that shaped their respective genomes were consistent. High-depth targeted massively parallel sequencing of sporadic synchronous EECs/EOCs from 17 additional patients confirmed that these lesions are clonally related. In an additional Lynch Syndrome case, however, the EEC and EOC were found to constitute independent cancers lacking somatic mutations in common. Taken together, sporadic synchronous EECs/EOCs are clonally related and likely constitute dissemination from one site to the other.
Many women with ovarian endometrioid carcinoma present with concurrent endometrial carcinoma. Organ-confined and low-grade synchronous endometrial and ovarian tumors (SEOs) clinically behave as independent primary tumors rather than a single advanced-stage carcinoma. We used 18 SEOs to investigate the ancestral relationship between the endometrial and ovarian components. Based on both targeted and exome sequencing, 17 of 18 patient cases of simultaneous cancer of the endometrium and ovary from our series showed evidence of a clonal relationship, ie, primary tumor and metastasis. Eleven patient cases fulfilled clinicopathological criteria that would lead to classification as independent endometrial and ovarian primary carcinomas, including being of FIGO stage T1a/1A, with organ-restricted growth and without surface involvement; 10 of 11 of these cases showed evidence of clonality. Our observations suggest that the disseminating cells amongst SEOs are restricted to physically accessible and microenvironment-compatible sites yet remain indolent, without the capacity for further dissemination.
new release: B.C. is taking the right approach to managing cancer of uterus and ovary (dual early stage primaries)
BC Cancer Agency
....The scientists explain the apparent paradox of the same cancer appearing simultaneously as two independent early-stage tumours on two different organs by invoking a novel process they call “pseudo-metastasis”. They propose that the process is distinct from usual metastasis in that the cancer likely spreads through the fallopian tube, not the blood stream, and that the host organs (ovary and uterus) provide a unique environment where these cancers are initially constrained.
“Pseudo-metastasis is still something of a mystery,” says Dr. Michael Anglesio, lead author and Research Associate in the department of Molecular Oncology at the BC Cancer Agency. “Whether the initial event takes place in the ovary or the endometrium, and what keeps cells temporarily restricted to these special organs without metastasizing to the rest of the body, are things that we are now researching.”.....
.....Meanwhile, a highly complementary study from Memorial Sloan Kettering Cancer Center (MSKCC), published in the same issue of JNCI, is giving both research teams overwhelming confidence in their findings.
“We are delighted that the findings of our studies are in agreement,” says Dr. Britta Weigelt, Assistant Member of the Department of Pathology at MSKCC. “Together, these studies have resulted in a paradigm shift in the way SEO cancers are perceived. By bringing together pathology and genetics, we have solved a long standing biological question and clinical dilemma.”....
Monday, February 08, 2016
Continuous Low-Dose Oral Cyclophosphamide and Methotrexate as Maintenance Therapy in Patients With Advanced Ovarian Carcinoma After Complete CR to Platinum + Paclitaxel Chemotherapy
open access - Egypt
Continuous Low-Dose Oral Cyclophosphamide and Methotrexate as Maintenance Therapy in Patients With Advanced Ovarian Carcinoma After Complete Clinical Response to Platinum and Paclitaxel Chemotherapy
Purpose: The aim of this study was to evaluate efficacy and safety of continuous, low dose of oral, metronomic chemotherapy as maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy.
Patients and Methods: In this nonrandomized study, patients older than 18 years, with Eastern Cooperative Oncology Group performance status less than 2, with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy were enrolled in 2 arms-arm A (maintenance arm), treated with continuous low-dose oral cyclophosphamide 50 mg and methotrexate 2.5 mg, and arm B (observation arm). Both arms were followed up for progression-free survival and toxicity.
Results: Thirty patients were accrued in each arm from January 2009 to December 2010 in Ain Shams University Hospitals, where they received the treatment and followed up for disease progression and toxicity. Patients had a median age of 53 years in maintenance arm and 52.5 years in the observational arm, respectively. Over 80% had papillary serous adenocarcinoma, and over 40% of them had a stage IV disease in both arms. After median follow-up of 27 months, patients achieved median progression-free survival of 18 months in maintenance arm (A) and 15.5 months in observational arm (B), respectively. Toxicity profile was excellent with no grade 3 or 4 toxicity reported.
Conclusions: Current study may provide an evidence of efficacy and tolerability of continuous low-dose oral cyclophosphamide and methotrexate as a maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy.
2) The study findings were presented on January 11 at the 2016 Cancer Survivorship Symposium in San Francisco