21 Jan 2013

Cancer Focus: Surgery for Ovarian Cancer

Gynecologic Oncologists Have Better Outcomes Than Surgeons Treating Ovarian Cancer
(reprinted with permission from Gregory Pawelski)

Elderly women with ovarian cancer tend to survive longer when treated by gynecologic oncologists than by general surgeons, according to results of a meta-analysis published in the Journal of the National Cancer Institute for February 1.

Dr. Craig C. Earle, from Dana-Farber Cancer Center in Boston, and his colleagues analyzed data from the Surveillance, Epidemiology and End Results (SEER) program for 3067 women aged 65 or older who underwent surgery for pathologically confirmed invasive epithelial ovarian cancer between 1992 and 1999.

These data were linked to Medicare data and American Medical Association files to obtain information about medical care they received and specialty type of the surgeon who performed cancer-related procedures. Records showed that 33% were operated on by a gynecologic oncologist, 45% by a general gynecologist, and 22% by a general surgeon.

Patients with stage I or stage II disease treated by gynecologic oncologists were more likely to undergo lymph node dissection (60% versus 36% by general gynecologists and 16% by general surgeons).

Those treated by gynecologic oncologists and general gynecologists were more likely to undergo a debulking procedure at the time of their first surgery than those operated on by general surgeons (58%, 51% and 40%, respectively) and to receive postoperative chemotherapy (79%, 76%, 62%).

Even though patients operated on by gynecologic oncologists tended to have more advanced disease at diagnosis, their survival rates were similar to those operated on by general gynecologists and better than those operated on by general surgeons (median survival 32.5 months, 35.6 months, and 24.3 months, respectively).

"Our data support professional societies' recommendations that it is preferable for ovarian cancer patients to be operated on by gynecologic oncologists when possible," Dr. Earle's group concludes.

SOURCE: J Natl Cancer Inst 2006;98:163-180.

Gregory D. Pawelski

17 Jan 2013

Cancer Focus: Pap Test for OVCA by G. Pawelski

'Pap' test possible for Ovarian Cancer?
(reprinted with permission from Gregory Pawelski)

Using cervical fluid obtained during routine Pap tests, scientists at the Johns Hopkins Kimmel Cancer Center have developed a test to detect ovarian and endometrial cancers. In a pilot study, the "PapGene" test, which relies on genomic sequencing of cancer-specific mutations, accurately detected all 24 (100 percent) endometrial cancers and nine of 22 (41 percent) ovarian cancers. Results of the experiments are published in the journal, Science Translational Medicine.

The investigators note that larger scale studies are needed before clinical implementation can begin, but they believe the test has the potential to pioneer genomic-based cancer screening tests.

The Papanicolaou (Pap) test, during which cells collected from the cervix are examined for microscopic signs of cancer, is widely and successfully used to screen for cervical cancers. However, no routine screening method is available for ovarian or endometrial cancers.

Since the Pap test occasionally contains cells shed from the ovaries or endometrium, cancer cells arising from these organs could be present in the fluid as well, says Luis Diaz, M.D., associate professor of oncology at Johns Hopkins and director of the Swim Across America Laboratory. The Laboratory is sponsored by a volunteer organization that raises funds for cancer research. "Our genomic sequencing approach may offer the potential to detect these cancer cells in a scalable and cost effective way," adds Diaz.

Cervical fluid of patients with gynecologic cancer carries normal cellular DNA mixed together with DNA from cancer cells, according to the investigators. Their task was to use genomic sequencing to distinguish cancerous from normal DNA.

The scientists had to determine the most common genetic changes in ovarian and endometrial cancers in order to prioritize which genomic regions to include in their test. They searched publically-available genome-wide studies of ovarian cancer, including those done by other Johns Hopkins investigators, to find ovarian-cancer specific mutations. Such genome-wide studies were not available for the most common type of endometrial cancer, so they conducted genome-wide sequencing studies on 22 of these endometrial cancers.

From the ovarian and endometrial cancer genome data, the Johns Hopkins-led team identified 12 of the most frequently mutated genes in both cancers and developed the PapGene test with this insight in mind.

The investigators then applied PapGene on Pap test samples from ovarian and endometrial cancer patients at The Johns Hopkins Hospital, Memorial Sloan-Kettering Cancer Center, the University of Sao Paulo in Brazil and ILSBio, a tissue bank. The new test detected both early and late stage disease in the endometrial and ovarian cancers tested. No healthy women in the control group were misclassified as having cancer.

The investigators' next steps include applying PapGene on more samples and working to increase the test's sensitivity in detecting ovarian cancer. "Performing the test at different times during the menstrual cycle, inserting the cervical brush deeper into the cervical canal, and assessing more regions of the genome may boost the sensitivity," says Chetan Bettegowda, M.D., Ph.D., assistant professor of neurosurgery at Johns Hopkins.

Together, ovarian and endometrial cancers are diagnosed in nearly 70,000 women in the United States each year, and about one-third of them will die from it.

"Genomic-based tests could help detect ovarian and endometrial cancers early enough to cure more of them," says graduate student Yuxuan Wang, who notes that the cost of the test could be similar to current cervical fluid HPV testing, which is less than $100.

PapGene is a high-sensitivity approach for the detection of cancer-specific DNA mutations, according to the investigators; however, false mutations can be erroneously created during the many steps - including amplification, sequencing, and analysis - required to prepare the DNA collected from a Pap test specimen for sequencing. The investigators needed to build a safeguard into PapGene's sequencing method, designed to weed out artifacts that could lead to misleading test results.

"If unaccounted for, artifacts could lead to a false positive test result and incorrectly indicate that a healthy person has cancer," says graduate student Isaac Kinde.

Kinde added a unique genetic barcode - a random set of 14 DNA base pairs - to each DNA fragment at an initial stage of the sample preparation process. Although each DNA fragment is copied many times before eventually being sequenced, all of the newly-copied DNA can be traced back to one original DNA molecule through their genetic barcodes. If the copies originating from the same DNA molecule do not all contain the same mutation, then an artifact is suspected and the mutation is disregarded. However, bonafide mutations, which exist in the sample before the initial barcoding step, will be present in all of the copies originating from the original DNA molecule.


Funding for the research was provided by Swim Across America, the Commonwealth Fund, the Hilton-Ludwig Cancer Prevention Initiative, the Virgina and D.K. Ludwig Fund for Cancer Research, the Experimental Therapeutics Center of Memorial Sloan-Kettering Cancer Center, the Chia Family Foundation, The Honorable Tina Brozman Foundation, The United Negro College Fund-Merck Graduate Science Dissertation Fellowship, the Burroughs Wellcome Career Award for Medical Scientists, the National Colorectal Cancer Research Alliance and the National Institutes of Health's National Cancer Center (N01-CN-43309, CA129825, CA43460).

In addition to Kinde, Bettegowda, Wang and Diaz, investigators participating in the research include Jian Wu, Nishant Agrawal, Ie-Ming Shih, Robert Kurman, Robert Giuntoli, Richard Roden, James R. Eshleman from Johns Hopkins; Nickolas Papadopoulos, Kenneth Kinzler and Bert Vogelstein from the Ludwig Center at Johns Hopkins; Fanny Dao and Douglas A. Levine from Memorial Sloan-Kettering Cancer Center; Jesus Paula Carvalho and Suely Kazue Nagahashi Marie from the University of Sao Paulo. Papadopoulos, Kinzler, Vogelstein and Diaz are co-founders of Inostics and Personal Genome Diagnostics. They own stocks in the companies and are members of their Scientific Advisory Boards. Inostics and Personal Genome Diagnostics have licensed several patent applications from Johns Hopkins. These relationships are subject to certain restrictions under The Johns Hopkins University policy, and the terms of these arrangements are managed by the University in accordance with its conflict-of-interest policies.

Citation: Johns Hopkins Medicine. "Detecting Ovarian, Endometrial Cancers Using "PapGene" Test." Medical News Today. MediLexicon, Intl., 11 Jan. 2013

Gregory D. Pawelski

Cancer Focus Reprints

Sunflower Sisters is pleased to announce that we have obtained permission from Gregory Pawelski, author and moderator of the Cancer Focus website, a forum for PhD's, to reprint his commentaries on ovarian cancer. 

In his own words - "I was a spouse/caregiver to an ovarian cancer patient. I became intensely interested in cancer medicine by virtue of working through, enduring and surviving my wife's illness. My college education (I trained as a political economist) and experience helped me to gather knowledge by virtue of voluminous reading and hundreds of hours of past and ongoing personal communication with noted authorities and experts in the field. Although now retired, privately, I've been a cancer patient advocate...my point...is to educate patients and others..." 

Here is a link to his wife's story http://www.cancerlynx.com/pawelski.html

Sunflower Sisters will post Greg's commentaries as and when they appear on his website.  For past postings or registration go to:  www.cancerfocus.org

Survivorship/Caregiver Program

We have been contacted by a representative of the Canadian Cancer Society to help them publicize a course that they are offering nationally to survivors and caregivers called Living Well Beyond Cancer.

The program has been licenced to them by Stanford University and was originally developed to help patients with chronic illnesses.  The new program has been tailored to meet the needs of post-treatment cancer survivors and caregivers, dealing with all aspects of everyday life.

It is an intimate learning/sharing environment limited to ten people per class and can be scheduled to accommodate the participants' availability.

For information and registration in your area, please call the Canadian Cancer Society:

9 Jan 2013

Never Assume

Yesterday was checkup day and as usual, it was a long one.  I sometimes take advantage of the wait by chatting with other "patient" patients.    

This story started with me seeing a lady and her husband come out of an examining room ahead of an older woman whom they had accompanied.  The younger woman plunked her purse and coat down on the chair beside me and to no one in particular said that she was completely confused.  I asked her if I could help and she said she didn't know.  I thought she was talking about her bearings - how to get to the right window for appointment bookings, where the blood lab is etc.  She laughed a kind of not happy laugh and said she just didn't understand.  Trying to pick up on her laughing, I said that I sincerely hoped that she never had to understand this place...to which she responded "it looks like we may have to".  Oh my...

Then she repeated "I don't understand...I just don't understand".  I looked at her.  She started to mumble that she had no idea what they were doing at a cancer clinic.  She said that her mother had been operated on recently resulting in the removal of a 14 pound tumour.  They said they "got it all".  So, what are we doing here??  The gyn/onc surgeon that they had just consulted told them that she thought that the mother's tumour was the result of ovarian cancer.  "Not possible" they all said.  "Mother had a hysterectomy ten years ago.  How can she possibly have ovarian cancer with no ovaries?"  The doctor told them that before this latest surgery, she still had ovaries.

The family was understandably reeling in shock and disbelief. 

After hearing this I too was stunned and then finally said "I'm so sorry". 

What could anyone say?  Where did the fault lie when all those years ago incorrect assumptions were made?  The patient is now 75 years old.  How does she adjust to all of these new realities?  What happens when she goes back to her original surgeon and asks the questions that should have been posed ten years earlier?  Was it standard procedure at that time to leave the ovaries in a 65 year old woman?  Should there have been heightened surveillance in view of her medical history?

This family's story represents a very sad lesson in reinforcing the importance of participating fully in all aspects of your healthcare and more importantly, in never assuming.