Cancer patients rarely demand unnecessary tests and treatments

Physicians often blame patient demands for contributing to high medical costs, however, a new study involving more than 5,000 patient-clinician visits indicates that cancer patients rarely push for unnecessary tests and treatments from their health care providers.

The study, conducted by Ezekiel Emanuel, MD, PhD and colleagues in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania and published in the inaugural issue of JAMA Oncology, examined a total of 5,050 patient-clinician encounters, and found that 440 (8.7 percent) of those included a patient demand or request for a medical intervention. Clinicians complied with 365 of the demands they deemed clinically appropriate. However, of the 50 demands requesting clinically inappropriate tests or treatments, clinicians only complied with seven (0.14 percent of the 5,050 encounters).

About half of the requests (49.1 percent) were for imaging studies, 13.6 percent were for laboratory tests such as tumor markers, and 5.2 percent were for genetic tests or chemosensitivity tests. Surprisingly, 15.5 percent of patient demands or requests were for palliative care interventions, such as pain medications and sleeping aides. Just 3.6 percent of patient demands or requests were for chemotherapy, and less than one percent for expensive proton beam therapy.

We decided to look specifically at cancer patients’ demands because oncology is a setting where there are life-and-death stakes for patients and the drugs and tests can get very expensive,” said senior author Emanuel, chair of the department of Medical Ethics and Health Policy at Penn. “However, we found, contrary to expectations, that patient demands are low and cannot be a key driver of increasing health care costs.”

The Penn Medicine team surveyed 60 clinicians — including 34 oncologists, 11 oncology fellows, and 15 nurse practitioners and physician assistants — immediately after patient encounters at three Philadelphia Hospitals (The Hospital of the University of Pennsylvania, Penn Presbyterian Medical Center and Pennsylvania Hospital) between October 2013 and June 2014. The goals of the interviews were to determine frequency of patient requests or demands for tests and treatments, whether those requests were appropriate, whether they were granted and why.

The study also found that patients who had worse relationships with their physicians, and those on active therapy, were more likely to make demands or requests for tests or treatments.

We observed very few patient demands for inappropriate treatments, and it was even rarer that a physician complied with the demand,” said lead author Keerthi Gogineni, MD, MSHP, who was an instructor in Penn’s Abramson Cancer Center when the study was conducted and is now a faculty member at Emory University. “In this age of unregulated consumer medical information on the Internet, it’s encouraging to see that this hasn’t translated to cancer patients requesting inappropriate — and often costly — tests and treatments.”

Gogineni et al. Patient Demands and Requests for Cancer Tests and Treatments. JAMA Oncol. 2015;  doi:10.1001/jamaoncol.2014.197 [Article]

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Young adult survivors most distressed after leukemia and lymphoma treatment

Two University of Colorado Cancer Center studies published in the Journal of Psychosocial Oncology show that young adult survivors (ages 18-39) of leukemia and lymphoma are more likely to report high distress than older survivors (ages 65+). Specifically, 45 percent of younger patients report moderate-to-high distress, whereas only 18 percent of older patients report similarly elevated levels. Interestingly, in both groups this distress was not affected by time since treatment – distress was just as likely to be high in survivors who had completed treatment four years prior as in survivors who were three months out of treatment.

Now that patients are living longer with cancer and after cancer, it is becoming more and more important to look at how survivors are living. What is their quality of life and how can we help make it better?” says Whitney Jones, PhD, the studies’ first author, working with data collected by Carly Parry, PhD, research scientist at Kaiser Permanente, California. Both Jones and Parry are family members of cancer survivors. Jones says, “It was natural – I just kind of fell into survivorship research.”

Jones explains the effect of age on distress using a framework called the Lifespan Perspective. Because there is an expected social, cultural and developmental course of a person’s life, an event (such as cancer) that is highly disruptive in one lifespan stage may be less disruptive in another.

For younger survivors, cancer is out of context,” Jones says. “When you’re under forty, you’re finishing your education, entering the workforce, starting a family, and cancer may be interpreted as disruptive and unexpected in that phase. On the other hand, some of our older survivors said things like, ‘Cancer isn’t the most difficult thing I’ve experienced in life.’ And they knew friends and family members who had dealt with similar cancer experiences,” she says.

One paper surveyed 477 cancer survivors, using a widely-used measure of distress after trauma and several items from a measure of quality of life in cancer survivors. These measures allowed Jones, Parry and colleagues to ask which factors of a cancer survivor’s life after treatment are the best predictors of persistent distress after treatment completion. Survivors under age 40 had the highest prevalence of distress, while a risk profile showed that a person’s fear of cancer recurrence was the best predictor of elevated distress – people who feared recurrence were most likely to also report high overall distress levels. High financial burden due to cancer treatment also predicted distress.

The second study used interviews with 51 leukemia survivors to explore the human side of these numbers and better understand the sources of distress as articulated by survivors themselves.

For example, this was before the Affordable Care Act, and we had one survivor who talked about having only the basic college student insurance when he was diagnosed. After treatment he discovered he had substantial medical debt and was uninsurable. It helped to hear survivors talk about their experiences in their own words. To hear them articulate it helped us understand the real struggles behind our data,” Jones says.

Interviews may also help explain why distress lingers even years after treatment ends.

A patient told us that, after lymphoma treatment, her doctor said that it would take two years to recover physically and mentally, and that almost all the gains would be in these two years,” Jones says. “She said something like, ‘I was really patient for two years, then after those two years passed, I didn’t feel any better and realized this is what I was going to be living with.'”

Distress detection and treatment is increasingly being seen as part of the standard of care for cancer patients and post-treatment survivors. For example, organizations like the National Comprehensive Cancer Network (NCCN) and the American College of Surgeons Commission on Cancer (ACS CoC) mandate distress screening and treatment in order to earn accreditation from these institutions.

Understanding which individuals are most likely to experience elevated distress,” for example young adult survivors who report fear of recurrence and financial strain due to cancer, “can be useful in targeting interventions to potential participants,” Jones says.

Jones et al. Understanding Distress in Post-Treatment Adult Leukemia and Lymphoma Survivors: A Lifespan Perspective. J Psycho Oncol. 2015; DOI:10.1080/07347332.2014.1002658 [Abstract]

Jones et al. Prevalence and Predictors of Distress in Post-Treatment Adult Leukemia and Lymphoma Survivors. J Psycho Oncol. 2015; DOI:10.1080/07347332.2014.992085 [Abstract]

One-two punch catches cancer cells in vulnerable state

Timing may be decisive when it comes to overcoming cancer’s ability to evade treatment. By hitting breast cancer cells with a targeted therapeutic immediately after chemotherapy, researchers from Brigham and Women’s Hospital (BWH) were able to target cancer cells during a transitional stage when they were most vulnerable, killing cells and shrinking tumors in the lab and in pre-clinical models. The team reports its findings in Nature Communications.

We were studying the fundamentals of how resistance develops and looking to understand what drives relapse. What we found is a new paradigm for thinking about chemotherapy,” said senior author Shiladitya Sengupta, PhD, associate bioengineer at BWH.

Previous studies have examined cancer stem cells (CSCs) – small populations of cells within a tumor that are resistant to chemotherapy. Sengupta and his colleagues took breast cancer cells that did not have the markings of CSCs and exposed them to docetaxel, a common chemotherapy drug.

This confocal microscopy image depicts drug-tolerant cancer cells. By hitting breast cancer cells with a targeted therapeutic immediately after chemotherapy, researchers were able to target cancer cells during a transitional stage when they were most vulnerable. Credit: Aaron Goldman

The team found that after exposure to chemotherapy, the cells began developing physical markings usually seen in CSCs, including receptors on the cell surface to which specific proteins can bind. These “markers of stemness” suggested that the cells were transitioning into a different state, during which time they might be vulnerable to other cancer drugs.

To test this, the researchers treated the cells with a variety of targeted therapeutics immediately after chemotherapy. The researchers observed that two drugs each killed a large fraction of the cells that had begun transitioning: dasatinib, a drug that targets the Src Family Kinase (SFK) and RK20449, a new drug in pre-clinical testing that specifically targets one of the SFK proteins called Hck. The researchers confirmed these findings in a mammary carcinoma mouse model – treatment with dasatinib just a few days after administering two high doses of chemotherapy prevented tumor growth and increased survival rates. Treating cells simultaneously with docetaxal and dasatinib or administering dasatinib after a longer period of time did not produce the same effects. The researchers theorize that the cancer cells go through a temporary transition state, which means that administering the drugs in a very specific timeframe and sequence is important.

By treating with chemotherapy, we’re driving cells through a transition state and creating vulnerabilities,” said first author Aaron Goldman, PhD, a postdoctoral fellow in biomedical engineering at BWH. “This opens up the door: we can then try out different combinations and regimens to find the most effective way to kill the cells and inhibit tumor growth.

To make these observations, the researchers developed and leveraged three-dimensional “explants” – tissue derived from a patient’s tumor biopsy and grown in serum from that specific patient for research purposes. This model mimics the tumor’s microenvironment and preserves the tumor’s cellular diversity.

In a continuation of this work, Goldman is also using mathematical modeling to pursue the most effective dose of chemotherapy to induce the vulnerable transition state of the cancer cell demonstrated in this research.

Our goal is to build a regimen that will be efficacious for clinical trials,” said Goldman. “Once we understand specific timing, sequence of drug delivery and dosage better, it will be easier to translate these findings clinically.”

Goldman et al. Temporally sequenced anticancer drugs overcome adaptive resistance by targeting a vulnerable chemotherapy-induced phenotypic transition. 2015; Nature Comm. 6: 6139 doi:10.1038/ncomms7139 [Article]

Twelve-year study suggests procedures to prevent cervical cancer do not affect fertility

Common surgical procedures used to diagnose and treat precancerous cervical lesions do not decrease women’s chances of becoming pregnant, according to a study that followed nearly 100,000 women for up to 12 years.

To the contrary, researchers found that women who had one of these procedures were actually more likely to become pregnant than women who did not have a procedure. The new Kaiser Permanente study is published today in PLOS ONE.

According to the Centers for Disease Control and Prevention, about 3 million women in the United States will have an unclear or abnormal pap test each year. Many of them will go on to have a diagnostic colposcopy and biopsy to determine if they have pre-cancerous lesions on their cervix. If these lesions are found, the women may have a LEEP procedure, cryotherapy or another surgical procedure to remove the cells so they don’t progress to cervical cancer.

This is great news for the millions of women who have one of these procedures, but still want to have a family,” said Allison Naleway, PhD, lead author and senior investigator at the Kaiser Permanente Center for Health Research in Portland, Oregon. “There was a fear that these procedures could weaken the cervix, and reduce fertility, but our study suggests that this is not the case.”

The researchers examined medical records for 4,137 women between the ages of 14 and 53 who were members of the Kaiser Permanente health plan in the states of Oregon and Washington between 1998 and 2009 and who had had a cervical treatment procedure. They followed the women for up to 12 years after the procedure to find out if they became pregnant. The researchers compared those women to 81,435 women in the health plan who did not have a cervical treatment procedure and 13,676 who had a colposcopy or biopsy diagnostic procedure.

Fourteen percent of women who had cervical treatment procedures got pregnant, compared to 9 percent of women who did not have a procedure and 11 percent of women who had a biopsy or colposcopy. After adjusting for age, contraceptive use and infertility, women who had a treatment procedure were still almost 1.5 times more likely to conceive compared to untreated women. Pregnancy rates among women who had a biopsy or colposcopy were the same as rates among women who had a surgical treatment procedure.

While the data we collected did not include sexual history, it is possible that the women who had these procedures may have been more sexually active than the untreated group, and that would explain the higher pregnancy rates,” Naleway said.

This is the largest study to date to examine whether these surgical procedures decrease fertility. Other, smaller studies have relied on patient recall and survey data rather than examination of medical records, which was what Naleway used for her study.

Researchers also examined whether these procedures affected birth outcomes such as preterm delivery. Results of that study are expected later this year.

Naleway et al. Pregnancy after treatment for cervical cancer precursor lesions in a retrospective matched cohort. PLoS ONE. 2015; 10(2): e0117525. doi:10.1371/journal.pone.0117525 [Article]