Cancer treatment in 2014: Making the most of research
Cancer will be defeated not in one enormous advance, experts agree, but in incremental advances. Those incremental advances often go unnoticed by the public at the time of their discovery, but in the years to come, they add up – to more life years, to greater survival rates, to more time spent with families and loved ones.
In 2014, patients will begin to see the benefits of many of those advances. Here, City of Hope's physicians describe some of the recent scientific and medical developments they expect to benefit patients in the year ahead.
Breast cancer: A first-step therapy, now taken more seriously
Breast cancer remains a leading cancer killer of women (second only to lung cancer), but Joanne Mortimer, M.D., director of City of Hope's Women's Cancers Program, pointed to several studies that could begin to have a positive impact on treatment and survival.
The most significant recent development, she said, is the use of the monoclonal antibody pertuzumab as pretherapy (more formally known as neoadjuvant therapy) in HER2-positive breast cancer that has advanced locally. Such disease can be difficult to treat – and time is of the essence – so the Food and Drug Administration (FDA) earlier this year approved pertuzumab as neoadjuvant therapy when used along with the drugs Herceptin and docetaxel.
Such early treatment in high-risk patients is considered crucial to effectively fighting the disease.
"The results of this trial paved the way for using response to neoadjuvant chemotherapy as a surrogate for response and benefit to treatment of metastatic disease," Mortimer said.
Other recent research suggests more effective therapies for women with metastatic disease. Mortimer pointed to a study that found neither mastectomy or lumpectomy and radiation were of benefit in treating the primary cancer, either initially or after response to systemic therapy.
"That suggests surgery may actually result in more rapid progression of metastatic disease," she said. "In the absence of pain or local problems, mastectomy should not be performed outside of a clinical trial in this population."
Cervical cancer: A notable drug advance and a simple, but powerful, test
Adding one drug to a treatment regimen can often have a significant difference; that appears to be the case with cervical cancer and the drug bevacizumab, which slows the growth of new blood vessels.
Robert J. Morgan M.D., co-director of the Gynecological Oncology/Peritoneal Malignancy Program at City of Hope, explained a recent study evaluating the role of the drug in addition to chemotherapy in metastatic carcinoma of the uterine cervix. "The addition of bevacizumab to chemotherapy resulted in a survival benefit from 13.3 months to an improved 17 months with very acceptable toxicity," Morgan said.
"This is the first study that has resulted in a meaningful survival benefit for recurrent cervical cancer compared to the 'standard' chemotherapy of cisplatin and paclitaxel," he added.
But cervical cancer must be detected before it can be treated and, for many parts of the world, that detection remains a significant hurdle. Recent findings could begin to change the outlook.
"In India, a study was carried out that used a simple method of identifying potential cervical cancers in areas that are too poor to have access to pap smear technology," Morgan said. The method? The application of vinegar.
"Using trained observers and using acetic acid (vinegar) on the cervix, many early cervical cancers were identified," Morgan said. "It is estimated that the mortality rate of this illness can be slashed by up to one third by this simple technique. "
He added: "It is still though important, particularly in this country, that women obtain regular gynecologic care and also that pre-teens and teenagers obtain the HPV vaccine."
Endometrial (uterine) cancer: Understanding molecular changes
To fight a disease, doctors need to understand it.
"One problem with uterine and all gynecologic cancer is that we have not had a good understanding of how molecular changes in combination with histology may be beneficial in directing treatments," said Morgan, also a professor and associate director for medical education in the Department of Medical Oncology & Therapeutics Research at City of Hope.
One recent study has improved that understanding considerably, giving researchers new avenues to explore. Morgan points to a large study using the Cancer Genome Atlas that analyzed molecular characteristics of 373 endometrial cancers, including low-grade endometrioid cancers, high-grade endometrioid cancers and papillary serous cancers. Researchers were able to identify four new categories of endometrial cancer based on the molecular characterizations of the tumors.
"This may well lead to treatment decisions based on molecular markers in addition to histological markers and allow better treatment with targeted agents," Morgan said. "For example, one subset of high-grade endometrioid tumors had p53 mutations similar to papillary serous tumors, and the supposition is made that these may respond better to treatments designed for serous tumors."
For women with endometrial cancer – and the doctors treating them – that kind of research-based guidance will be crucial to better outcomes.
Lung cancer: The benefit of precision therapies
In treating lung cancer, think "precision."
Karen L. Reckamp, M.D. M.S., co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope, said physicians are increasingly using information on the genomics of lung tumors. With this information, they can better block cancer growth and improve outcomes by providing precision therapy for patients.
“In addition, we are beginning to understand the impact of activating the immune system to enhance the attack on tumor cells," Reckamp said. "We may see a day when a patient's own immune system can be directed against lung cancer.”
Meanwhile, Dan J. Raz, M.D., co-director of the Lung Cancer and Thoracic Oncology Program at City of Hope, is emphasizing the importance of screening.
“Lung cancer screening is recommended by the U.S. Preventive Services Task Force," he said. "Widespread adoption of lung cancer screening with low-dose radiation CT scanning has the potential to dramatically reduce death from lung cancer and turn lung cancer into a disease that is detected at an early stage a majority of the time.”
Ovarian cancer: Improved treatments on the way
The treatment of ovarian cancer is becoming both more effective and more complex.
"There are problems with the current standard treatments of ovarian cancer, including the fact that our treatments are similar despite differences in histology and grading of the tumors," acknowledged Morgan. He cites a lack of research in smaller subsets of ovarian cancer and a lack of effective alternative therapies, despite the development of many targeted agents in the past decade.
But several developments suggest room for improvement in the coming year. For starters, a new drug, salumetinib, is showing promise against low-grade ovarian tumors that have been very difficult to treat. Further, Morgan added: "More agents directed at specific genomic mutations should result in improved treatments in the next few years."
He also said that treatments could become easier on the patients themselves, pointing to new research on weekly schedules of the chemotherapy drugs carboplatin and taxol that suggests the regimen is just as effective, but less toxic than more traditional regimens.
Meanwhile, ongoing research into the PARP inhibitor olaparib suggests that it may improve treatment of hereditary ovarian cancers when used in the maintenance setting and that the angiogenesis inhibitor cediranib could improve survival in recurrent ovarian cancer.
More research is needed on these drugs before they can be used routinely, but the potential is promising.
Drugs aren't the only option. "At City of Hope, we are collaborating in a T cell study investigating whether immune therapy may be beneficial in specific subsets of ovarian cancer patients," Morgan said. "This is based on new knowledge of the immune system and how it plays a role in ovarian cancer."
Pancreatic cancer: A novel approach to improve survivability
Pancreatic cancer's lethal reputation comes from its stealth. As Gagandeep Singh, M.D., interim chair of the Department of Surgery at City of Hope, described the disease: "Fifty percent of pancreatic cancer is diagnosed at Stage IV, i.e., after it has spread, giving it a very bleak outlook."
On the positive side, he noted, 50 percent of patients do not have metastatic disease. "While only 10 percent are operable at the time of diagnosis, the remaining 35 to 40 percent are considered locally advanced," he said. "We strive to make these 40 percent operable, too, by a combination of neoadjuvant chemotherapy with radiotherapy followed by aggressive surgery or just aggressive surgery up front."
Singh is optimistic about the future, especially as it relates to improvements in a procedure known as the Whipple, which involves the removal of the head of the pancreas along with the bile duct and the upper part of the intestine. During the surgery, tissue from the intestine is used to reconstruct the bile system, intestine and pancreas.
"We have been able to harness the advantage of the robot to do robotic-assisted Whipples by inserting hand-simulated instruments through tiny holes and then conducting the operation through these keyhole incisions," Singh said. "The magnification, coupled with ease of use of these robotic instruments, adds to better and more radical clearance of the cancer."
But choosing the right institution is crucial. "This is what is key – making sure those patients that have nonmetastatic pancreatic cancer go to the right institution at the right time to improve their survivability," Singh said.
Prostate cancer: Using fluorescents to target disease
Timothy Wilson, M.D., the Pauline & Martin Collins Family Chair in Urology at City of Hope and director of the Prostate Cancer Program, has high hopes for doctors increasing ability to see precisely where cancerous cells stop and non-diseased cells begin. The key is fluorescence.
"The concept is the fluorescent label antibody against an antigen that sits on prostate cells, cancerous or not," Wilson said. "You inject the fluorescent label antibody into the patient; it then targets and locates the prostate cell. And then during surgery, while doing it robotically, a switch is flipped that lights up that fluorescent label antibody so you see prostate tissue."
He added: "This helps make sure we get all the cancer out or will help us see prostate cancer cells in lymph nodes."
City of Hope plans to begin a clinical trial of that technique within months. It's also exploring how to improve active surveillance, also known as "watchful waiting," in men who have prostate cancer but who may not need immediate treatment. One method uses magnetic resonance imaging assessment of the prostate; another uses biomarkers.
Wilson referred specifically to the promise of a biomarker study by Steven Smith, Ph.D., professor of molecular science, urology and urologic oncology, that could help determine which men should stay on active surveillance and which men should receive treatment.
Radiation oncology: Getting a clear picture
For Jeffrey Wong, M.D., chair of City of Hope’s Department of Radiation Oncology, the future is looking not only brighter, but much clearer.
“There are two exciting trends for the field with the integration of imaging in radiation oncology," he said. One involves what's known as SBRT, for stereotactic body radiation therapy. This type of therapy uses very precise, very concentrated beams of radiation directed directly at the tumor. The other trend to watch uses ultrafocused sound with magnetic resonance imaging.
"For patients who refuse surgery or are medically unable to have surgery, SBRT can be used for lung patients with a 90 percent effectiveness in controlling the cancer," Wong said.
As for magnetic resonance-guided focused ultrasound, or MRgFUS, it's currently being evaluated by the Food and Drug Administration and is being tested to ablate prostate cancer, Wong said.
City of Hope's Vicky Hoffman contributed to this report.