The National Comprehensive Cancer Network (NCCN) recently updated the NCCN Guidelines for Ovarian Cancer to include two additional combination treatment regimens for women with select types of recurring ovarian cancer.
These modifications made to the NCCN Guidelines for ovarian cancer are based on results from recent studies in The Lancet and The Journal of Clinical Oncology demonstrating that both combination regimens improved medianprogression-free survival in women with specific types of recurring ovarian cancer as compared to conventional regimens. In addition, the carboplatin/weekly paclitaxel regimen improved overall survival.
Robert J. Morgan, Jr., M.D., F.A.C.P., Professor, Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center
“Ovarian cancer is a challenge to treat because by the time the majority of the women are diagnosed with the disease, it has already progressed to stage III or IV,” says Robert J. Morgan, MD, of City of Hope Comprehensive Cancer Center and the chair of the NCCN Guidelines Panel for Ovarian Cancer. “Although finding effective screening tools remains a priority, new treatment options for women with ovarian cancer such as the ones outlined in the updated NCCN Guidelines, remains imperative to making steady progress against the disease.”
Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and the country’s fifth most common cause of cancer mortality in women. In the year 2009, there were more than 21,000 new diagnoses and nearly 15,000 deaths from this neoplasm in the United States.
The National Comprehensive Cancer Network (NCCN), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives.
How do you define tragedy? … The loss of Archibald “Moonlight” Graham and Sue-Louise Newmann is certainly tragic, however, their lives exemplify hope and inspiration.
Alabama Crimson Tide 37 — Texas Longhorns 21. That was the final score of the Citi BCS National Championship football game, which was played in the Rose Bowl on January 7, 2010. The Texas team experienced a major setback in that game when quarterback Colt McCoy, a 2008 Heisman Trophy Finalist, was injured during the first quarter of the game. More specifically, the Texas quarterback was injured on the fifth play of the game. At that moment, all football fans understood the significance of the injury in light of the following records held by Colt McCoy at game’s start: highest NCAA single season passing completion percentage (77.6%); highest NCAA career passing completion percentage (70.9%); and most NCAA football game wins by a starting quarterback (44).
I watched that BCS National Championship game with a friend. Immediately after Marcell Dareus –an Alabama defensive lineman — hit McCoy, and it was clear that the Texas starting quarterback would not return to the game due to a shoulder injury, my friend exclaimed: “That’s a tragedy!” He elaborated upon his initial comment by describing how important McCoy was to the Texas football team and how Texas’ chance for victory walked off the field along with its injured quarterback. In total dismay, my friend went on to described how important this game was to Colt McCoy and his future National Football League career and related compensation package.
Shortly after football game ended in a Texas defeat, I began to think about my friend’s comment. It seemed fair in the heat of a sporting moment. A few hours later, it seems outright ridiculous. I began to think about what most people consider “a tragedy” in life, and what, if any, example(s) could be used to appropriately define this term in the context of an individual’s life. Two individuals came to mind as a way to place a human face on the proper meaning of the term: Dr. Archibald “Moonlight” Graham and Sue-Louise Newmann.
Dr. Archibald “Moonlight” Graham
Archibald “Moonlight” Graham was an American professional baseball player who appeared as a right fielder in a single major league game for the New York Giants on June 29, 1905. His story was popularized by Shoeless Joe, a novel by W. P. Kinsella, and the subsequent 1989 Oscar-Nominated “Best Picture” Field of Dreams, starring Kevin Costner, and featuring Burt Lancaster and Frank Whaley as older and younger incarnations of “Moonlight” Graham. On June 29, 1905, the Giants were the visiting team against the Brooklyn Superbas. In the bottom of the eighth inning of that baseball game, Graham was sent in to play right field, replacing George Browne. In the top of the ninth inning, Graham was on deck to bat next when his teammate Claude Elliott flied out resulting in the third and final out. Graham played the bottom of the ninth inning in right field but never came to bat, and that game turned out to be his only appearance in the major leagues.
After playing in the minor baseball leagues through the 1908 season, Graham completed his medical degree from the University of Maryland in 1908. He obtained his medical license the following year and began his practice in Chisholm, Minnesota. According to Veda Ponikvar, founder of The Chisholm Free Press and Tribune, Graham jumped on a train to Minnesota after reading a small ad listing a doctor’s position. Once in Chisholm, Graham never left. He lived in Chisholm until his death 54 years later in 1965. “Doc” Graham, as he became known after his career as a ballplayer, served the people of Chisholm for fifty years. From 1915 to 1959, Graham was the doctor for the Chisholm public schools.
In the movie Field of Dreams, Iowa farmer Ray Kinsella (Kevin Costner) hears a disembodied voice in his cornfield, telling him “If you build it, he will come.” This mysterious occurrence leads Ray into the past, on an unexpected cross-country journey, and in search of an elusive connection with his long deceased father. This is a magical film about the transformative power of baseball, the love of a son for his father, and believing in something that you can’t quite define in words. In the later part of the movie, a mystical clue leads Ray to Chisholm, Minnesota. Once in Chisholm, Ray meets the reincarnated spirit of elderly “Doc” Graham.” Graham tells Ray the story of his life including his single appearance in a major league baseball game — a game in which he never batted. The movie dialogue below provides one example of the proper definition of “tragedy” in the context of an individual’s life:
Dr. Archibald "Moonlight" Graham as portrayed by Burt Lancaster in the 1989 "Best Picture" Oscar-Nominated movie "Field of Dreams."
Dr. Archibald “Moonlight” Graham: Well, you know I… I never got to bat in the major leagues. I would have liked to have had that chance. Just once. To stare down a big league pitcher. To stare him down, and just as he goes into his windup, wink. Make him think you know something he doesn’t. That’s what I wish for. Chance to squint at a sky so blue that it hurts your eyes just to look at it. To feel the tingling in your arm as you connect with the ball. To run the bases – stretch a double into a triple, and flop face-first into third, wrap your arms around the bag. That’s my wish, Ray Kinsella. That’s my wish. And is there enough magic out there in the moonlight to make this dream come true?
Ray Kinsella: Fifty years ago, for five minutes you came within… y-you came this close. It would KILL some men to get so close to their dream and not touch it. God, they’d consider it a tragedy.
Dr. Archibald “Moonlight” Graham: Son, if I’d only gotten to be a doctor for five minutes… now that would have been a tragedy.
Ray, like my friend, defined “tragedy” in the context of a kid’s game that turned professional. “Moonlight” Graham would have been one of fiction’s (and Hollywood’s) great characters, except for the fact that “Moonlight” Graham was a real person. He really did become the beloved town doctor of Chisholm, Minnesota. And, he really did play in just one major league baseball game. That one game was played over 100 years ago, and was the subject of a msnbc feature narrated by Keith Olbermann, entitled Moonlight Graham Remembered.
Shortly after his death in 1965, Veda Ponikvar wrote the following obituary for Dr. Archibald Graham in the local Chisholm newspaper:
As the community grew, Doc became an integral part of the population. There were good years and lean ones. There were times when children could not afford eyeglasses, or milk, or clothing because of the economic upheavals, strikes, and depressions. Yet no child was ever denied these essentials, because in the background, there was a benevolent, understanding Doctor Graham. Without a word, without any fanfare or publicity, the glasses or the milk, or the ticket to the ball game found their way into the child’s pocket.
A person would be fortunate to possess the qualities embodied by “Moonlight Graham;” humility, grace, kindness, hope and inspiration. Dr. Graham is a genuine example of a life well-spent. Archibald “Moonlight” Graham, in life, and as portrayed in the movie, understands the true meaning of the word “tragedy.”
Sue-Louise Newmann
Did you ever sense the inner character an individual without ever meeting that person? I did, and her name is Sue-Louise Newmann. About a week ago, I was updating the Libby’s H*O*P*E* ovarian cancer video library when I came across three YouTube videos posted by Sue-Louise Newmann’s husband. Each video consists of a picture montage set to music. The picture montages reveal the couple’s special life moments such as getting married, having children, celebrating birthdays and anniversaries, and traveling overseas. The background music playing in each video was composed and sung by Sue-Louise.
In terms of “internet presence,” I only discovered a limited amount of information about Sue-Louise Newmann. Sue-Louise was married and a mother to two young daughters. She lived in Australia. Newmann was also the head of human resources for an Australian utility company. As a gifted songwriter and muscian, she played many of the instruments that were used to record her songs.
Sue-Louise was diagnosed with ovarian cancer in 2006, and she died in February 2009 at the age of 46. The three songs that accompany the video picture montages were recorded by Sue-Louise after her doctor informed her that she would likely live for only nine more months. The video titles (and the song titles) are Time of My Life, Waiting For a Miracle, and Don’t You Forget About Me. I extend my highest gratitude to Sue-Louise’s husband for creating and publicly sharing these videos.
Time of My Life
Despite the fact that I never met Sue-Louise, the video picture montages leave no doubt that her life was filled with love, family, and music. Sue-Louise’s inner character shines bright in each picture. I believe that Sue-Louise possessed “ordinary grace,” a term coined by the author Kathleen Brehony in her book bearing the same title. In that book, Brehony explains that ordinary grace does not only live in great cathedrals and holy ashrams, it lives in ordinary people who have found a place in their lives for love, generosity and simple kindness. Sue-Louise’s ordinary grace manifests itself in her pictures, as well as the notes and lyrics of her songs. In proper context, the death of Sue-Louise Newmann, as a wife, a mother, a friend and a talented songwriter, is clearly a tragedy. The loss of any women from ovarian cancer is a tragedy.
From Tragedy Comes Hope & Inspiration
The loss of Archibald “Moonlight” Graham and Sue-Louise Newmann is certainly tragic, however, their lives exemplify hope and inspiration. Dr. Graham turned the loss of a professional baseball career into a life of helping others through medicine and random acts of kindness. Sue-Louise Newmann also lived a full life. When confronted with imminent death from ovarian cancer, Newmann chose to write and sing beautiful songs that will forever touch and inspire us. Each individual, when faced with difficulty or life-threatening circumstances, chose to inspire hope in others. In the end, such inspiration creates an everlasting legacy that transcends death.
So, the next time you experience a bad day, a career disappointment, an angry driver, or a curt salesperson, take a moment to realize that these events do not rise to the level of a tragedy. And, at the end of each day, ask yourself the following question: “How will I be remembered in my eulogy or tribute video?”
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*”Vox Populi,” a Latin phrase that means “voice of the people,” is a term often used in broadcast journalism to describe an interview of the “man on the street.”
In the spirit of Vox Populi, Libby’s H*O*P*E*™ searches online for original pieces of writing or visual media created by ovarian cancer survivors, survivors’ family members, cancer advocates, journalists, and health care professionals, which address one or more aspects of ovarian cancer within the context of daily life. The written and visual media features that we discover run the gamut; sometimes poignant, sometimes educational, sometimes touching, sometimes comedic, but always honest. The Vox Populi feature may take the form of an essay, editorial, poem, letter, story, song or picture montage.
It is our hope that the Vox Populi feature will allow our readers to obtain, in some small way, a better understanding of how ovarian cancer impacts the life of a woman diagnosed with the disease and her family. We invite all readers to submit, or bring to our attention, original written or visual media pieces suitable for publication as Vox Populi features.
Fred Hutchinson Cancer Center researchers discovered that concentrations of the serum biomarkers CA125, human epididymis protein 4 (HE4), and mesothelin began to rise 3 years before clinical diagnosis of ovarian cancer, according to a new study published online December 30 in the Journal of the National Cancer Institute. However, the biomarkers became substantially elevated only in the last year prior to diagnosis. … In an accompanying editorial to the study results reported by Anderson et. al., Patricia Hartge, ScD, of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, applauds the researchers for taking the field one step closer to successful screening study designs by showing that the levels of certain biomarkers do not increase early enough to be used for screening.
Garnet L. Anderson, Ph.D., Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.
CA125, HE4, mesothelin, B7-H4, decoy receptor 3, and spondin-2 have been identified as potential ovarian cancer serum biomarkers, but their behavior in the prediagnostic period, with the exception of CA125, has not been evaluated. In the JNCI study, Garnet L. Anderson, Ph.D., of the Division of Public Health Sciences at the Fred Hutchinson Cancer Research Center in Seattle, and colleagues analyzed prediagnostic serum samples and patient data from the Carotene and Retinol Efficacy Trial (CARET), a randomized, double-blind, placebo-controlledchemoprevention trial testing the effects of beta-carotene and retinol on lung cancer incidence among individuals at high risk for lung cancer. Prediagnostic serum samples (taken up to 18 years prior to diagnosis) were obtained for 34 CARET patients with ovarian cancer and 70 matched control CARET subjects. Changes in the levels of these biomarkers prior to ovarian cancer diagnosis were analyzed.
Anderson et. al. discovered that concentrations of CA125, HE4, and mesothelin (but not B7-H4, decoy receptor 3, and spondin-2) began to increase slightly in cancer patients relative to control subjects approximately 3 years before diagnosis, but became substantially elevated within one year prior to diagnosis. Thus, the diagnostic value of these biomarkers is limited because accuracy only increased shortly before diagnosis. “Although these markers are not accurate enough to prompt early intervention in existing screening protocols, the multivariable regression analyses identified modest but statistically significant increases in risk associated with CA125, HE4, and mesothelin, which are consistent with many of the established epidemiological risk factors for ovarian cancer,” say the authors of the study.
“I still think biomarkers may play a role in a cost-effective screening program, although none of these seem accurate enough either alone or together to justify their use in average-risk women,” Anderson told Medscape Oncology. “I do not know of any other currently identified biomarkers that hold more promise than these, but there has been a massive effort over the last few years to identify candidates and not all have been thoroughly vetted,” said Dr. Anderson.
One problem, cites Dr. Anderson, may lie in the approach used in identifying potential ovarian cancer biomarkers. “Most of the discovery work done so far has been conducted in women with advanced-stage disease and compared them to healthy women,” she explained. “If discovery work were done in samples like the ones we used here, representing specimens collected months to years prior to the advanced stage diagnosis, we might have a better chance of finding earlier signals of aggressive disease.”
Another opportunity for improving screening and early diagnosis lies in imaging, she adds. “Currently the most common and only affordable imaging option that could be considered for routine screening is transvaginal ultrasound, but it performs poorly in terms of accurately determining those women [who] have ovarian cancer from those who do not,” said Dr. Anderson. “A substantial improvement in this area would be very exciting.”
Study Limitations Cited By JNCI Editors
The JNCI editors state three limitations that they believe are associated with the study by Anderson et. al. First, the study sample size was small. Second, all women who participated in CARET had a history of heavy smoking, and therefore, the JNCI editors believe that the blood serum testing results obtained by Anderson et. al. may not apply to other non-smoking groups. Third, the blood collected from women participating in CARET was collected at different times, but only a few samples were collected during the last 2–3 years before ovarian cancer diagnosis.
Designing Ovarian Cancer Early Detection Programs — Accompanying JNCI Editorial
Patricia Hartge, Sc.D. Deputy Director, Epidemiology and Biostatistics Program, Division of Cancer Epidemiology & Genetic, National Cancer Institute
Dr. Hartge notes that despite the discovery that CA125 and other serum markers increase before the clinical onset of ovarian cancer, it has been exceedingly difficult to devise a successful ovarian cancer early screening program for asymptomatic women. Nevertheless, Hartge believes that Anderson et al. take a valuable step toward the design of such a successful screening program by demonstrating why screening regimens that are based on markers, or panels of markers, can fail. Specifically, the researchers discovered that blood levels of CA125, HE4, mesothelin, and three other promising markers did not increase early enough in the course of the disease to allow detection in early stages. Dr. Hartge emphasizes that the markers typically rose within one year of the disease symptoms that led to an accurate diagnosis, and therefore, many of the ovarian cancer patients were diagnosed with advanced stage disease.
Hartge further states “[t]hat the results of Anderson et al. are not the last word in serum markers or in combinations of markers.” “Serum markers likely will form a key element in any screening regimen, with the lead time and other parameters of each marker or combination of markers being taken into account. The careful evaluation technique applied in the current study fits into a staged approach necessary for testing performance of early markers of disease.” Hartge adds that “[o]nly the time-consuming, expensive, and demanding randomized clinical trial can reveal whether an early detection program that includes the biomarkers can save lives.”
In support of her position, Dr. Hartge observes that current randomized trials are testing the value of different screening programs that are built on combinations of CA125, ultrasound, and risk factor data (e.g., family history and age). After four rounds of screening 34,261 postmenopausal women for ovarian cancer with both CA125 and ultrasound, University of Alabama at Birmingham School of Medicine investigators of the large U.S. screening trial observed that the predictive value of a positive screen was quite low — approximately 1%. Of the 60 screen-detected cancers, 72% had already advanced to at least stage III. [3] In addition, of every 20 women who underwent surgery after a positive screen, only one women was diagnosed with cancer. Furthermore, in a recent UK trial with a slightly different design, positive predictive values from the first round of screening were higher; 35% in the 50,078 women whose risk was assessed with CA125 and risk factor data, followed by ultrasound only if indicated, and 3% in the 50,639 women screened first with ultrasound. [4] The effects on mortality in both trials remain to be determined.
Confronting The “Daunting Arithmetic” Required To Detect Early Stage Ovarian Cancer
Based upon the foregoing, Dr. Hartge highlights the “daunting arithmetic” required to detect early stage ovarian cancer. In the U.S., Surveillance, Epidemiology and End Results (SEER) data indicates that incidence amounts to 13 cases of ovarian cancer per 100,000 woman per year, referred to by Dr. Hartge as the “proverbial needles in the haystack.” [5] So as not to present a problem without a potential solution, Hartge provides a roadmap to additional factors that may help future researchers develop early screening methods to identify those rare cases of ovarian cancer in the general population. Notably, SEER data also indicates that incidence of ovarian cancer steadily increases with age from 21 cases per 100,000 women per year within the 50-54 age range to 57 cases per 100,000 women per year within the 80-84 age range. [6] Furthermore, family history, low parity, and more ovulations over a woman’s lifetime predict additional risk, with the strongest but least common predictor being a mutation in the BRCA1 or BRCA2 gene. Thus, the general approach suggested by Hartge focuses on women with higher baseline risks, for whom the predictive value of a positive serum test tends to increase. Dr. Hartge believes that the performance of an overall screening program will improve by targeting higher-risk subgroups of women for screening by combining personal history, genetic abnormality status, and levels of serum markers in one prediction model. With ongoing advances in understanding the origin and causes of ovarian cancer, Hartge states that the risk models that are useful for screening programs should also improve.
Further technology advancements may also improve future ovarian cancer early detection screening models, says Hartege. For example, a screening program that is based on a panel of biomarkers can be improved by developing new medical imaging technology that is more specific than current ultrasound technology. If better imaging existed, fewer women would undergo surgery following a suspicious biomarker finding. Similarly, development of less invasive surgery could further reduce harmful side effects. Although Hartge observes that a highly accurate biomarker(s) or an overall screening program does not yet exist, she also explains that the current study by Anderson et. al., with its sobering implications, brings future researchers closer to understanding the crucial elements in designing an effective early detection program for ovarian cancer.
5/ Horner MJ, Ries LAG, Krapcho M, et al, eds. SEER Cancer Stat Fact Sheets (2009) Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/statfacts/html/ovary.html. Accessed December 2, 2009.
The National Comprehensive Cancer Network (NCCN) recently updated the NCCN Clinical Practice Guidelines for Oncology™ for Ovarian Cancer to reflect the addition of two preferred combination regimens for a specific cohort of patients based on data from recent clinical research studies.
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