Doctors at Washington University School of Medicine in St. Louis have shown that testing cervical tumors before treatment for vulnerability to chemotherapy predicts whether patients will do well or poorly with standard treatment. The study supports the future possibility of personalized medicine for cervical cancer, a tumor normally addressed with a one-size-fits-all approach.
“Even though this is a small study, its strength is that it links a lab test of the tumor’s chemotherapy response to survival outcomes for the patients,” said Julie K. Schwarz, MD, PhD, assistant professor of radiation oncology. “Very few cancers have been studied this way, and this is the first such report for cervical cancer.”
Since 1999, nearly all cervical cancer cases have been treated the same way: daily radiation therapy targeted to the tumor plus a weekly intravenous infusion of the chemotherapy drug cisplatin.
“We believe that radiation does the majority of the work with cervical cancer,” said Schwarz, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “But a randomized trial published in 1999 showed that combining it with cisplatin chemotherapy improved survival outcomes.”
Even today, according to Schwarz, doctors have no way of knowing who will do well or poorly with the combined radiation and chemotherapy that every patient receives. Now, Schwarz and her colleagues have shown that the tumor’s response to chemotherapy, independent of radiation, may be a major deciding factor in whether a patient will do well with the standard treatment.
The study appears online in the journal Gynecologic Oncology.
“This is evidence that cisplatin is not just helping the radiation work better,” Schwarz said. “It is having some direct toxic effect on cancer cells that may be hiding elsewhere in the body, some place where the radiation is not hitting it, since we target the radiation so precisely to the main tumor. We think it would be beneficial for that drug to be selected appropriately for the patient’s individual tumor.”
A cervical tumor is a tumor, or abnormal growth, on the cervix and is a condition that primarily indicates cervical cancer. Cervical cancer is the second leading type of cancer in women, behind breast cancer. A cervical tumor results from abnormal cell growth and has been linked to the human papilloma virus, for which there is now a vaccine for certain strains. Cervical cancer can be detected with a laboratory test that examines cervical cells obtained through a gynecological procedure called a Pap test.
Like other types of cancer, cervical cancer is staged based on characteristics. Staging depends on the formation of a cervical tumor and whether or not the cervical tumor is confined to the cervix alone or has metastasized to other areas of the vagina or pelvis.
The most effective way of screening for cervical cancer is through routine cervical Pap tests. Though not all women receive routine screening, those that do have a better chance of early diagnosis and treatment. Many women become fearful of abnormal results from cervical pap tests, but doctors generally order a second test within three months to confirm an abnormality since other factors can contribute to abnormal results.
The investigators tested tumors from 33 cervical cancer patients before their treatment began. They divided the patients’ tumors into three categories – responsive, intermediate response and nonresponsive – based on how well cisplatin killed the tumor cells growing in a dish.
For tumors categorized as responsive – those cancer cells that cisplatin killed most easily – 100 percent of the patients were alive and disease-free after two years. For those that showed an intermediate response, 83 percent of the patients were alive and disease-free after two years. And for those tumors deemed nonresponsive, only 58 percent of patients had two-year disease-free survival.
Cervical cancers can be divided into two main types based on how they look under a microscope – squamous cell carcinoma and adenocarcinoma. The nonresponsive number was even worse for patients diagnosed with the more common squamous cell carcinoma, with 46 percent disease-free survival at two years.
Pap testing has decreased the death rate from cervical cancer greatly over the last 50 years. However, in 2009, an estimated 11,270 new cases of cervical cancer will be diagnosed in the U.S.
Infection with HPV, or human papillomavirus, is the main cause of cervical cancer. When exposed to HPV, a woman’s immune system usually prevents the virus from causing harm. The virus survives in a small percentage of women though and eventually it turns cells on the surface of the cervix into cancerous cells. Half of cases of cervical cancer occur in women ages 35-55.
HPV infection and other risk factors may act together to increase the risk. Other risk factors include a weakened immune system, smoking, sexual history, using birth control pill for 5 or more years, having 5 or more children, or a lack of regular Pap tests which help doctors find abnormal cells.
“Ideally, we would like to be able to design clinical trials for the nonresponsive patients,” Schwarz said. “One chemotherapy drug isn’t working for everyone, but there isn’t going to be one explanation for why the chemo doesn’t work. It’s going to be 50 different explanations, and figuring that out is the challenge.”
Schwarz is quick to point out the weaknesses of this study. In addition to the small number of patients, the lab test used was not ideal and should not be used to decide therapy for patients, she said. The investigators initially evaluated 75 tumors for chemotherapy response. And though some patients’ data was not included because they did not adhere to the treatment regimen, 31 patients were excluded from the analysis because their tumor cells did not grow well in the lab.
“This is definitely not the definitive test,” Schwarz said. “But I think our results should prompt investigators to think outside the box and start generating new ideas about how best to treat this disease. The bottom line is a one-size-fits-all treatment for each patient is going by the wayside. As we develop personalized strategies, this is the sort of testing that can guide it.”
Julie K. Schwarz is supported by a K12 career development grant from the National Institutes of Health (NIH), grant number 5K12HD00145910.
Grigsby PW, Zighelboim I, Powell MA, Mutch DG, Schwarz JK. In vitro chemoresponse to cisplatin and outcomes in cervical cancer. Gynecologic Oncology. Published online before print April 13, 2013. doi: 10.1016/j.ygyno.2013.04.005
Washington University School of Medicine’s 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked sixth in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.
The Siteman Cancer Center, the only National Cancer Institute-designated Comprehensive Cancer Center in Missouri, is ranked a top 10 cancer facility by U.S. News & World Report. Comprising the cancer research, prevention and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine, Siteman is also Missouri’s only member of the National Comprehensive Cancer Network.
By Julia Evangelou Strait