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Commentary
Saturday, August 27, 2016
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Clinical Actionability of Comprehensive Genomic Profiling for Management of Rare or Refractory Cancers
the Oncologist
Background. The frequency with which targeted tumor sequencing
results will lead to implemented change in care is unclear.
Prospective assessment of the feasibility and limitations
of using genomic sequencing is critically important.
Methods. A prospective clinical study was conducted on 100
patients with diverse-histology, rare, or poor-prognosis cancers
to evaluate the clinical actionability of a Clinical Laboratory
Improvement Amendments (CLIA)-certified, comprehensive
genomic profiling assay (FoundationOne), using formalin-fixed,
paraffin-embedded tumors. The primary objectives were to
assess utility, feasibility, and limitations of genomic sequencing
for genomically guided therapy or other clinical purpose in the
setting of a multidisciplinary molecular tumor board.....
RESULTS
Genomic Spectrum Reflects Both Intertumoral and Tumor Type–Specific Commonalities
Four pediatric and 96 adult patients with rare histology or refractory
cancers underwent tumor genomic profiling for a varied spectrum
of epithelial and mesenchymal origin tumors (supplemental online
Figs. 1, 2; supplemental online Table 1). At enrollment, 91% of
patients were stage IV and had received a mean of 2.5 prior
therapies.....
Dr. Robert Coleman on BRCA Testing in Ovarian Cancer (video 1:34 min)
Dr. Robert Coleman (onclive)
Aug 26, 2016
Robert Coleman, MD, professor in the department of Gynecologic Oncology and Reproductive Medicine, University of Texas MD Anderson Cancer Center, discusses BRCA testing for ovarian cancer.
The current recommendations for BRCA testing say that high-grade serous patients should get it at the diagnosis. However, recent data has shown that other histology types have enough of a frequency that it's worth testing there as well, says Coleman. Outside mucinous tumors, germline testing has been done across the board, says Coleman.
Germline and somatic BRCA alterations look similar, says Coleman. There isn’t much data on other non-BRCA germline mutations that might be associated with familial or genetic risk, and what their likelihood is, but that field is expanding, says Coleman.
Spotlight on ASCO’s Geriatric Oncology Webpage - The ASCO Post
The ASCO Post
ASCO’s Web-Based Resource
Through a recent grant sponsored by the Association of Specialty Professors, ASCO, in conjunction with the Geriatric Oncology Special Interest Group, has been able to develop the first Web-based resource for many aspects pertaining to geriatric oncology, ranging from patient care to training (https://www.asco.org/practice-guidelines/cancer-care-initiatives/geriatric-oncology/geriatric-oncology-resources).
Currently, the geriatric oncology resource Webpage is divided into six main sections:....
Dear Health Minister Eric Hoskins – Concerned Ontario Doctors letter to healthcare minister
Dear Health Minister Eric Hoskins – letter
Dear Health Minister Eric Hoskins
Thank you for your letter on August 25, 2016.
A motivated profession is a productive profession. We stand united in our belief that you are wrong.
Doctors
want binding arbitration as it is our right. It was granted once to us,
and legislated away. So we have a challenge before the courts to get it
back. We’ll likely win, but it will take years. Until then, we will
continue to serve our patients.....
Aug 25th letter - legal opinion re: Ontario Doctors (OMA/Ontario Government)
legal opinion/history of events (pdf)
plus Twitter:
http://goo.gl/UKgTyY
Editorial: (Lynch et al) Rare diseases of the digestive system (case studies/publication)
Editorial: Rare diseases of the digestive system
... It appears clear to the editors that rare diseases involving the digestive system may have significant impact on the individual patients, public health, medical education and scientific advancement. There are currently 7,000 rare diseases identified [5, 17]. CD and Lynch syndrome are just two examples where case reports eventually led to critical scientific and clinical research findings, and benefited numerous patients. Many rare diseases, however, are poorly studied. Their etiopathogenesis, clinical presentation, diagnosis, management and prognosis are poorly defined. We therefore believe that there is an under-recognized need for more reports and studies on rare or uncommon diseases. A decision of accepting case reports in American Journal of Digestive Disease is thus made to meet such a need. While many journals have started eliminating the category of case report, we hope that this journal will offer a platform for publication of rare, yet interesting, cases with exceptional educational values. We are particularly interested in publishing cases with unique clinical, pathological and molecular features, ideally exceedingly rare yet clinically important. It is our hope that the publications will increase the awareness of rare diseases and thus strengthen the world-wide efforts in combating these diseases [5, 18].
We hope our decision of publishing case reports will contribute to the effort
The Dualistic Model of Ovarian Carcinogenesis - Revisited, Revised, and Expanded
abstract
full text (pdf)
Epithelial ovarian cancer and type of peritoneal insult: a case–control study
abstract:
Epithelial ovarian cancer and type of peritoneal insult: a case–control study - European Journal of Obstetrics and Gynecology and Reproductive Biology
Objective
To evaluate the association between different types of peritoneal insults and the development of sporadic epithelial ovarian cancer (EOC) subtypes in the general population.Study design
Hospital based case control study comparing sporadic cases of EOC with age matched control group between 2003 and 2008. Medical, surgical, and gynecological histories were compared between 208 women with histological diagnosis of EOC and 224 women in the control group matched for age at presentation for well woman examination.MRI for discriminating metastatic ovarian tumors from primary epithelial ovarian cancers
Full Text
(small study/references to related research)
Published: 28 August 2015
Study subjects
This retrospective study was approved by the institutional review boards of Shanghai First People’s Hospital, Shanghai, China. The informed consent requirement was waived. We searched for data of patients with ovarian tumors from January 2012 to December 2014 on a hospital information system—a picture archiving and communication system (PACS). We encountered 11 consecutive cases (median age, 42 years; range, 21–58 years) of metastatic ovarian tumors confirmed by pathology. Six gastric cancers, two colon cancers, one cervical cancer, one breast cancer and one thyroid cancer were found among the patients. It is obvious that the most common site of primary origin of metastatic ovarian cancers was stomach. Meanwhile, we detected 26 consecutive cases (median age, 56 years; range, 17–82 years) with pathologically confirmed primary epithelial ovarian cancers. None of these cases witnessed the history of malignant tumors except the present cancers. All the primary epithelial ovarian cancers had undergone surgery. Then the cancers were confirmed by histopathological pathologists in Shanghai First People’s Hospital. Consequently, ten serous cystadenocarcinoma, six clear cell cancers, five borderline malignancy, three mucinouscystadenocarcinoma and two endometrioid adenocarcinomas were found (Table 1). (see below)Conclusions
In
conclusion, metastatic ovarian tumors seem to be smaller in size, more
bilateral, more uniform in locules and more moderate enhancement in
solid portions than those of primary ovarian cancers. Metastatic ovarian
tumors were with less elevated levels of CA125 and HE4 in contrast with
primary ovarian cancers. (note: see Table 3) Although the sensitivity, specificity, and
accuracy of any features are not sufficient for diagnoses, the
combination of three key features (patients’ age, small size, and
bilaterality) tends to have a high sensitivity, specificity, and
accuracy for identifying metastatic ovarian tumors. The radiologist must
depend on a combination of the imaging features as well as the clinical
examinations in order to diagnose metastatic ovarian tumors.
Table 1
Summary of the cases
Tumor type
|
Total cases
|
Histopathologically confirmed cases
| |
|---|---|---|---|
Metastatic ovarian tumors
|
Gastric cancer
|
6
|
6
|
Colon cancer
|
2
|
2
| |
Thyroid cancer
|
1
|
1
| |
Uterine cervical cancer
|
1
|
1
| |
Breast cancer
|
1
|
1
| |
Subtotal
|
11
|
11
| |
Primary ovarian tumors
|
Serous cystadenocarcinoma
|
10
|
10
|
Clear cell carcinoma
|
6
|
6
| |
Borderline malignancy
|
5
|
5
| |
Mucinous cystadenocarcinoma
|
3
|
3
| |
Endometrioid adenocarcinoma
|
2
|
2
| |
Subtotal
|
26
|
26
| |
Total
|
37
|
37
| |
Potential implications on female fertility and reproductive lifespan in BRCA germline mutation women
open access
First Online: 25 August 2016
Conclusions
BRCAm
women should not delay pregnancy, especially if they are BRCA1, older
than 35 years or with previous gonadotoxic treatments. Future
prospective studies on infertility outcomes in this population are
needed.
Consequences of the germline mutation on cancer risk are widely known, but not the non-oncological implications [2]. Controversy exists about the impact of BRCA1/2 germline mutations (BRCA1/2m) on female fertility [3]. There is a current interest in identifying the possible association between BRCA germline mutation (BRCAm) and reproductive performance [1]. Recent research articles suggest that BRCAm, especially BRCA1, decreases ovarian reserve [4], increases fertility-related problems [1] and determines early menopause (also known as premature or occult primary ovarian failure) [5] (Fig. 1).....
Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials
abstract:
Prognostic factors in young ovarian cancer patients: An analysis of four prospective phase III intergroup trials of the AGO Study Group, GINECO and NSGO
Highlights
Abstract
Objectives
We evaluated in a large study meta-database of prospectively randomised phase III trials the prognostic factors for progression-free survival (PFS) and overall survival (OS) in patients < and >40 years of age with advanced epithelial ovarian cancer.Methods
A total of 5055 patients of the AGO, GINECO, NSGO intergroup studies AGO-OVAR 3, 5, 7 and 9 were merged to identify 294 patients <40 years and 4761 patients ≥40 years. We conducted survival analyses and Cox proportional hazard regression models and additionally analysed a very homogeneous subcohort of 405 patients with serous epithelial ovarian cancer, excellent performance status, who had received complete macroscopic upfront cytoreduction and ≥5 chemotherapy cycles.Results
For patients <40 years, the median PFS was 28.9 months and the median OS was 75.3 months, while the median PFS for patients ≥40 years was 18.1 months and the median OS was 45.7 months. Independent prognostic factors were similar in both age groups. In a multivariate analysis including prognostic factors potentially leading to confounding, young age appeared to improve PFS and OS. The observed effect was even stronger in the subcohort of optimally treated patients with SEOC: PFS and OS.Discussion
Prognostic factors were similar in both age groups. Young age appeared a strong independent protective prognostic factor for PFS and OS in the subcohort.The dual role of complement in cancer and its implication in anti-tumor therapy
open access- Annals of Translational Medicine
(technical)
Review Article July 2016
The dual role of complement in cancer and its implication in anti-tumor therapy
1Department of Clinical Pathobiochemistry, Technische Universität Dresden, 01307 Dresden, Germany; 2Ovarian Cancer Research Center, University of Pennsylvania, Philadelphia, PA 19104-6160, USA
Contributions: (I) Conception and design: All authors;
(II) Administrative support: None; (III) Provision of study materials or
patients: None; (IV) Collection and assembly of data: None; (V) Data
analysis and interpretation: None; (VI) Manuscript writing: All authors;
(VII) Final approval of manuscript: All authors.Cochrane: search "cancer" eg. Gynaecology (92)
Search results ("cancer")
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New and updated
Podcasts
Has podcast (32)Friday, August 26, 2016
Gene testing in rare tumor type could uncover 'cancer families (sarcoma/BRCA...)
Science news
....They found that over half of 1,162 patients with sarcoma tested were born with mutations in at least one gene already known to increase cancer risk.
Some of the most common inherited mutations occurred in genes known to drive the development of multiple tumour types -- p53, APC, BRCA1 and BRCA2 -- putting these patients at increased risk of other cancers such as breast, ovarian or bowel cancer. When such mutations are found, families can be offered genetic counselling and screening, where appropriate....
A fifth of the patients had mutations in more than one of the genes tested and, importantly, people with genetic errors in multiple cancer genes were found to be more likely to get cancer at a younger age than those with a single genetic mutation. This is the first evidence that multiple genetic mutations interacting could be causing sarcomas in some patients, rather than a single gene driving their disease.abstract
Unfurling the Genetic Map of Sarcomas
Abstract
An international team of researchers has
uncovered multiple new germline mutations that may influence the
development of sarcomas.
Notably, they found that variants in several DNA
damage sensing and repair genes contribute greatly to sarcoma risk,
including
BRCA2, ATM, ATR, and ERCC2.
- ©2016 American Association for Cancer Research.
Individualised benefit–harm balance of aspirin as primary prevention measure – a good proof-of-concept, but could have been better… | BMC Medicine | Full Text
open access
BMC Medicine201614:101
Published: 6 July 2016
Abstract
Guidelines
from different organisations regarding the use of aspirin for primary
prevention vary despite being based on similar evidence. Translating
these in practice presents a further major challenge. The benefit–harm
balance tool developed by Puhan et al. (BMC Med
13:250, 2015) for aspirin can overcome some of these difficulties and
is therefore an important step towards personalised medicine. Although a
good proof-of-concept, this tool has some important limitations that
presently preclude its use in practice or for further research. One of
the major benefits of aspirin that has become apparent in the last
decade or so is its effect in preventing cancer and cancer-related
deaths. However, this benefit is clear and consistent in randomised as
well as observational evidence only for specific cancers. Additionally,
it has long lag-time and carry-over periods. These nuances of aspirin’s
effects demand a specific and a more sophisticated model such as a
time-varying model. Further refinement of this tool with respect to
these aspects is merited to make it ready for evaluation in qualitative
and quantitative studies with the goal of clinical utility.
Please see related article: http://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-015-0493-2
....After a thorough review of the evidence [8], we concluded that a clear and large benefit exists for colorectal, oesophageal and stomach cancer, and the benefit for lung, breast and prostate cancer is smaller and less clear. Many aspirin experts agree with a beneficial effect on only three gastrointestinal (GI) tract cancers due to the biological and pharmacological plausibility of such an effect [19], as well as due to some uncertainty regarding aspirin’s effects on lung, breast and prostate cancer. Therefore, we provided sensitivity analyses with aspirin’s beneficial effect being limited to three GI cancers as well as colorectal cancer alone [8]. Recent analyses by the U.S. Preventive Services Task Force also take into account only the beneficial effect on colorectal cancer [20]. Therefore, assuming aspirin’s effect on cancers other than colorectal, oesophageal, stomach, lung, breast and prostate cancers is not correct, even when simulations and repetitions consider the statistical uncertainty of effect on other cancers.....
Stem cell propagation fuels cancer risk in different organs
Medical News (research)
The results appear online today in the journal Cell.
Article: Multi-organ Mapping of Cancer Risk, Liqin Zhu, et al., Cell, doi: 10.1016/j.cell.2016.07.045, published 25 August 2016.
The scientists also showed that stem cells in newborn animals are far less likely to undergo malignant transformation than adult stem cells. This finding suggests that stem cells in the newborn are intrinsically resistant to the formation of tumors. "If this biology were to hold true in humans, then it may explain why cancer rates are many-fold lower in children than adults, despite the fact that childhood cancers accrue significant numbers of mutations that alter proteins, and that the growth rates of organs peak in childhood," said Zhu....
Port site metastatic disease in ovarian carcinoma (2015 small study)
abstract
Introduction
Port-site
metastases are a recognised complication of laparoscopy in the presence
of malignancy. With the increased use of minimally invasive technology
to surgically manage gynaecological malignancy, their incidence is
likely to increase. We describe three cases where patients underwent
laparoscopy prior to referral for definitive surgery.
Materials and methods
Patient
one attended a secondary centre complaining of urinary incontinence and
abdominal pain. Pre-operative imaging identified omental thickening and
ascites. Laparoscopy was performed and malignancy of the omentum and
peritoneum was identified in addition to a suspicious appearing ovary.
The second case concerned a 65 year-old patient presented with abdominal
pain and underwent emergent laparoscopy in which adenocarcinoma of the
ovary was diagnosed. After biopsies were obtained, the patient was
referred for definitive surgical management. Patient three underwent
laparoscopy due to abdominal pain. Pre-operative imaging identified
ascites and a pelvic mass. Biopsies were taken at laparoscopy which
confirmed ovarian malignancy.
Results
All
three patients developed histologically proven port-site metastatic
disease prior to undergoing definitive surgical management.
Conclusion
In
all cases, port-site metastatic disease developed rapidly and was
clinically suspected at the time of definitive surgery. We recommend
that consideration be given towards removing port sites when performing
cytoreductive surgery for gynaecological malignancy.
Identification of therapeutic targets applicable to clinical strategies in ovarian cancer
open access (technical)
August 24, 2016
Table of Contents
Conclusions
Loss-of-function screen
followed by in vitro target validation using chemical inhibitors
identified clinically relevant targets. This approach has the potential
to systematically refine therapeutic strategies in OC. These molecular
target-driven strategies may provide additional therapeutic options for
women whose tumors have become refractory to standard chemotherapy.
Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening
open access
Abnormal plasma DNA profiles in early ovarian cancer using a non-invasive prenatal testing platform: implications for cancer screening
The 32 cancer cases comprised 16 women with International Federation of Gynecology and Obstetrics (FIGO) stage I and II HGSOC (‘early cancer’), and 16 women with FIGO stages III and IV HGSOC (‘advanced cancer’). The control group included women with benign gynecologic disease undergoing surgery (n = 24), or germline BRCA1 and BRCA2 mutation carriers without evidence of malignancy who were undergoing risk-reduction surgery (n = 8).Discussion
In
this proof of concept study, low coverage plasma DNA sequencing and
analysis for chromosomal CNVs ≥ 15 Mb detected 40 % of HGSOC.
Surprisingly, we detected similar proportions of early and advanced
stage HGSOC cancers with this approach. This finding was unexpected
because one would assume a higher detection rate in the advanced stage
cases, given the lower tumor bulk of early disease. This suggests that
the detection of ovarian tumor CNVs in plasma is not directly related to
cancer stage; other biological factors such as fractional concentration
of tumor DNA in plasma, tumor genetic heterogeneity, vascularity, and
cell turnover may also be important influences on detection rates.....
Aug 12, 2016: Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (note blogger comments)
Ovarian Epithelial, Fallopian Tube, and Primary Peritoneal Cancer Treatment (PDQ®)
August 12, 2016
Estimated new cases and deaths from ovarian cancer in the United States in 2016:[5]
- New cases: 22,280.
- Deaths: 14,240.(Blogger's Note: this summary (above) does a poor job of referencing genetic links aside from the BRCA's)
- Lynch HT, Watson P, Lynch JF, et al.: Hereditary ovarian cancer. Heterogeneity in age at onset. Cancer 71 (2 Suppl): 573-81, 1993. [PubMed] [Reference list]
- Pennington KP, Swisher EM: Hereditary ovarian cancer: beyond the usual suspects. Gynecol Oncol 124 (2): 347-53, 2012. [PubMed] [Reference list]
‘We’ve been there’ the Metaxa oncologists who went public about their lives as patients + video
Cancerworld
Doctors get cancer too, but not many of them choose to make a documentary film about the experience. Vasiliki Michopoulou talked to some who did, and asked them why?
The emotions and insights generated by this ‘two-way’ battle would later be captured in a documentary by film director Stavros Psillakis. First shown in April 2012, Metaxa: Listening to Time heard not just from Karvounis, but from six other doctors at the cancer hospital who had themselves been diagnosed with cancer.ΜΕΤΑΧΑ listening to time. (video 1:26 min))
Newsroom : Minister Hoskin's letter to OMA (see blogger comment re: 'we")
Allow me to begin by reiterating my sincere disappointment in the outcome of the vote on the draft agreement that we both endorsed.
Blogger's Note: the 'we' refers to the government and the OMA made apparently without the knowledge or consent of the physicians - the 'battle' continues
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Newsroom : Minister Hoskin's letter to OMA
Ontario Newsroom
Minister Hoskin's letter to OMA
Virginia M. Walley, MD
Ontario Medical Association150 Bloor St. West, Suite 900
Toronto, Ontario M5S 3C1
Dear Dr. Walley,
I am writing in reply to your recent open letter with respect to physicians' compensation.
Allow me to begin by reiterating my sincere disappointment in the outcome of the vote on the draft agreement that we both endorsed.
Join the Ontario Genetic Advisory Committee - deadline Sept 6th
Health Quality Ontario (HQO)
The Ontario Genetic Advisory Committee, a proposed sub-committee of the Ontario Health Technology Advisory Committee, will review health technology assessments produced by Health Quality Ontario and advise on the clinical utility, validity, and value for money of new and existing genetic and genomic tests in Ontario.
The Ontario Health Technology Advisory Committee is appointed by the Health Quality Ontario Board of Directors and makes recommendations to the Minister of Health and Long-Term Care on which tests should be publicly funded.
We are seeking membership nominations for the following individuals from across Ontario to serve as members of the proposed Ontario Genetic Advisory Committee:
Patients and Caregivers with Lived Experience: Two individuals who can provide the patient perspective and are not employed in the health care sector. Read the role description.
Expected commitment:
- Participate in 4-8 meetings annually in Toronto, typically lasting 4 to 6 hours.
- Commit to a three year membership.
- Review documents circulated between meetings, and participate in occasional teleconference meetings.
For more information, please read the draft Terms of Reference for the proposed Ontario Genetic Advisory Committee.
Health Quality Ontario will be accepting applications until September 6th, 2016.
Novel Toxicity Examinations for Patients Treated With Targeted Therapies (research)
Blogger's Note: not exactly 'new' news - reference Q-TWiST google search (per below)
cancer research news
Prevalence assesses the rate of toxicity over time and can tease out some AEs that are resolved by medical intervention or spontaneous improvement with time. Q-TWiST (google search) can help evaluate the tradeoffs between toxicity and survival. This tool looks at toxicity, time without symptom and toxicity, and relapse. The researchers highlighted the strengths of these approaches in a phase 2 trial and a hypothetical simulated clinical trial.
Important advance made with new approach to 'control' cancer, not eliminate it (eg. ovarian cancer)
research news
August 26, 2016
Researchers have created a new drug delivery system that could improve the effectiveness of an emerging concept in cancer treatment - to dramatically slow and control tumors on a long-term, sustained basis, not necessarily aiming for their complete elimination.The approach, called a "metronomic dosage regimen," uses significantly lower doses of chemotherapeutic drugs but at more frequent time intervals. This would have multiple goals of killing cancer cells, creating a hostile biological environment for their growth, reducing toxicity from the drug regimen and avoiding the development of resistance to the cancer drugs being used.
A system just published in Chemistry of Materials by a group of researchers from Oregon and the United Kingdom offers an even more effective way to deliver such drugs and may be able to greatly improve this approach, scientists say. Further testing is needed in both animals and humans for safety and efficacy.
"This new system takes some existing cancer therapy drugs for ovarian cancer, delivers both of them at the same time and allows them to work synergistically," said Adam Alani, an associate professor in the Oregon State University/Oregon Health & Science University College of Pharmacy, and lead author on the new study.
"Imagine if we could manage cancer on a long-term basis as a chronic condition, like we now do high blood pressure or diabetes. This could be a huge leap forward."
This approach is still in trial stages, Alani said, but shows promise. In some prior work with related systems in animal tests, OSU and collaborating researchers have been able to completely eradicate tumors.....
More information: Deepa A. Rao et al, Combinatorial Polymeric Conjugated Micelles with Dual Cytotoxic and Antiangiogenic Effects for the Treatment of Ovarian Cancer, Chemistry of Materials (2016). DOI: 10.1021/acs.chemmater.6b01280
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