Liam Davenport

Disclosures

August 04, 2017

The American Society of Clinical Oncology (ASCO) Annual Meeting not only provides a focus for cancer specialists looking for updates on state-of-the-art treatments and novel therapies but also presents research directly related to primary care physicians (PCPs).

The following abstracts from the 2017 meeting in Chicago look at, among other topics, genetic and multimodal screening, the impact of lifestyle interventions on fatigue and survival, programs to help individuals navigate cancer screening, and novel interventions to reduce fear among cancer survivors and improve stress management in patients with newly diagnosed disease.

To provide takeaways on how the findings could influence primary care, Medscape asked two experts to discuss the research: William K. Oh, MD, chief of the Division of Hematology and Medical Oncology, and professor of medicine and urology at Icahn School of Medicine at Mount Sinai, New York, New York, who offered an oncologist's perspective; and Lewis E. Foxhall, MD, professor of clinical cancer prevention and associate professor in the Department of Family and Community Medicine at the MD Anderson Cancer Center, the University of Texas, Houston, Texas, who gave a more PCP-oriented interpretation.

Screening

Helping Smokers Navigate Lung Cancer Screening Can Improve Detection Rates

To examine the impact of a patient navigation tool on rates of lung cancer screening in community care, the study reported in abstract 1506 involved 1200 current smokers aged 55-77 years in five community health centers. They were randomly assigned in a 1:2 ratio to receive either the intervention, which involved cessation counseling, shared decision-making, scheduled appointments, reminders to order CT, and active follow-up, or usual care.

After 76 intervention-assigned patients declined to participate and 126 were deemed ineligible for screening, the team found that, in intention-to-treat analysis, lung cancer screening CT was performed in 94 (23.5%) intervention-group patients and 69 (8.6%) controls (P < .001). Lung cancer was subsequently diagnosed in eight (2.0%) intervention-group patients and four (0.5%) controls (P < .01).

Dr Oh: We know that over the past few years, randomized trials have demonstrated the benefit of lung cancer screening in smokers. The question of how well implemented it is remains unclear, because this requires active intervention, particularly by primary care doctors.

In this study, there was evidence that this approach really worked, particularly in community health centers, where lower-income smokers may not have the same access to some of the lung cancer screening guidelines as patients in private centers.

It really suggests, just like other studies have, that if you have a patient who is in a community health center, an active patient navigation may allow patients to have greater access to knowledge and to care that is potentially lifesaving.

Dr Foxhall: This is related to the relatively recent recommendations for lung cancer screening for community adults with high levels of tobacco exposure. They are basically using a navigator to help patients go through the recommended process, and it appears that it was useful, and a lot more people got screened. It is not clear what effect it had on their tobacco consumption, but it appears that it did guide people through the process.

It's a nice intervention; it seems to help. But it's not clear how that role would be filled in a primary care setting, unless perhaps a staff member could be trained, or perhaps the screening center could have a navigator who could be trained to do this sort of intervention and connect the patient back into primary care.

But this is certainly a good opportunity for screening; I think screening is still underutilized, and the ability to take advantage of screening opportunities to help encourage smoking cessation is important too.

Genetic Screening During Community Breast Imaging Identifies High-Risk Women

Although the National Comprehensive Cancer Network has published guidelines for the screening and testing of patients at hereditary risk for breast and ovarian cancer, the impact of screening genetic testing among women attending breast imaging centers is unclear.

For abstract 1507, the researchers therefore developed a guidelines-based screening tool that was added to the intake forms of almost 35,000 women undergoing breast imaging between 2012 and 2015. Of those, 1214 (3.5%) were flagged as potentially high-risk, of whom 189 had been genetically tested previously.

Of the remaining 1025 women, 258 (25.2%) made a genetic counseling appointment, 163 (15.9%) received genetic counseling, and 106 (10.3%) were tested for BRCA1 and BRCA2 mutations. Nine (0.9%) women tested positive for BRCA mutations, and eight (0.8%) were found to have a variant of unknown significance.

Dr Oh: We know that breast imaging centers are very high-throughput centers where women are getting mammograms, for which there may be an opportunity to assess them for other health risks.

Of those who were referred for genetic counseling, a significant proportion—up to 16%—wound up having a pathogenic mutation or one that could be of some concern for a BRCA mutation, which would change their subsequent follow-up. So it suggests that going to point of care for women who go for their mammography might allow you to detect some women who may be at greater risk for breast cancer.

Dr Foxhall: This was done by some of our MD Anderson team, so I have this disclosure.

It was an effort, through a questionnaire, to try to pick out people who might be candidates for counseling and testing, and to look for BRCA mutations. They found nine patients, but they had to screen 35,000 people. Although the intervention was fairly low-intensity and without any major downsides, in that they didn't need to do much more than ask to fill out a questionnaire, the yield in an otherwise generic population was fairly low.

But for those nine women who were positive, that was important. It's one of these trade-offs between volume and frequency, and it may well vary depending on the population involved.

Does Adding MRI to Mammography Improve Breast Cancer Survival?

The study reported in abstract 1508 included 3002 women with increased breast cancer risk, defined as a > 20% cumulative lifetime risk of developing breast cancer, who underwent two or more screening rounds between 2001 and 2005 and had ≥ 5 years' follow-up. Of the women, 1534 received combined MRI and mammography screening and 1468 received mammography screening alone.

The cancer yield with combined screening was 24.8 per 1000 women, versus 15.0 per 1000 women with mammography alone. Over a median follow-up of 10.8 years, there were six recurrences in the combined screening group and five in the mammography-only group. There were five deaths during follow-up, all in the mammography-only group.

Although there was no significant difference in disease-free survival with combined screening (P = .325), MRI plus mammography was associated with significantly better overall survival compared with mammography alone (P = .002).

Dr Oh: The results suggest, as we might expect, that the added sensitivity of MRI improves cancer detection. What was interesting, though, is that, when they looked at the disease-free and overall survival in this group, there was no difference in the disease-free survival, but the overall survival appeared to be better in the combined screening group compared to mammography only.

This not a prospective trial, so we have to be careful not to overinterpret it. But it does suggest that if you have more sensitive screening and you pick up cancers at an early stage, you might be able to alter overall survival. This needs to be validated in a more prospective study.

Dr Foxhall: There may have been some other factors in these groups that accounted for that the disease-free survival issues, but it certainly confirms the recommendation, which ASCO and others have agreed on, that people who don't want to go through surgery but are at high risk can do combined screening with MRI and mammography.

So, for people in the practice who have risk factors determined by a family history or BRCA genetic testing, that's certainly an important thing to do.

Lifestyle Modifications

Exercise May Reduce Breast Cancer Risk Among BRCA1 and BRCA2 Carriers

Can lifestyle interventions reduce an individual's genetic risk of developing cancer? This was the question tackled in abstract 1505, in which current and adolescent physical activity and smoking status was collected on 892 women from 279 families with a BRCA1/BRCA2 germ-line mutation, of whom 481 also answered a food-frequency questionnaire.

Women who exercised daily had a significantly reduced risk for breast cancer than sedentary women, with odds ratios (ORs) of 0.53 for current exercise (P = .043) and 0.40 for exercise in adolescence (P = .007). Women who exercise daily in both periods had an even lower risk (OR, 0.22; P < .001), and the effect was greater in premenopausal women.

Alcohol intake, smoking habits, and diet did not significantly alter the BRCA-associated risk of developing breast cancer.

Dr Oh: Looking at a population who have high risk for getting cancer but do not necessarily have cancer—the BRCA gene carriers—the researchers found that, particularly in younger women, the more physical exercise they did, the less likely they were to get breast cancer in particular.

So the question is: Does exercise improve the risk for cancer in a woman who may carry a BRCA1 or BRCA2 gene? This seems to suggest that it is one possible modifier of risk for breast cancer.

Dr Foxhall: I don't have the whole paper, so I'm not clear on how the groups matched up or how long they followed these individuals. But it's interesting that at the end of the study, the investigators felt that, all other things being fairly equal, people doing regular physical activity in this high-risk group had about one half the risk for breast cancer than that in the sedentary group.

Although correlation between physical activity and breast cancer risk has been demonstrated in other populations, it's interesting that, in this high-risk group, there appears to be a relatively significant difference. Again, I don't have the whole picture here, but certainly the conclusions of the abstract are very interesting.

These women, who we know are at increased risk, should be encouraged to maintain their physical activity or increase their physical activity if they're not doing it, because it is one of several interventions to help mitigate some of the risk involved in germline mutations.

Following Nutrition and Exercise Guidelines Improves Colon Cancer Survival

Abstract 10006 took a different slant on lifestyle interventions, in a study that asked whether following the American Cancer Society Nutrition and Physical Activity Guidelines for Cancer Survivors is indeed associated with improved survival outcomes in patients with colon cancer.

Among 992 patients with stage III colon cancer who underwent adjuvant chemotherapy between 1999 and 2001, there were 335 recurrences and 299 deaths over a median follow-up of 7 years.

A high score of 5-6 on McCullough and colleagues' scale of adherence to the guidelines, which was recorded in 9% of patients, was associated with a significantly lower risk for death compared with a score of 0-1 (seen in 26% of patients); the hazard ratio (HR) was 0.58 (P for trend = .01). They also had a trend toward improved disease-free survival (HR, 0.69; P for trend = .03). Adding alcohol intake into the analysis yielded similar results.

Dr Oh: This study seems to suggest that in patients who have curable cancer, all the things that we know are good for you may actually have a greater impact in terms of survival. What we don't know from studies such as this is whether patients who tend to adopt these behaviors also have other aspects that we don't recognize that may make them live longer.

But, in general, it suggests that these are good activities and behaviors to undertake.

Dr Foxhall: Patients with relatively advanced colon cancer who adhered more closely to the guidelines, especially in terms of body weight and physical activity, and consumed the recommended diet appeared to have fewer deaths than the comparison group.

Basically, it was confirmation that it's worthwhile trying to encourage our patients in these situations, even those with more advanced disease, to follow the recommended guidelines for activity.

Yoga Reduces Fatigue in Cancer Survivors, in Part by Improving Sleep

Abstract 10007 reported on one of two studies to examine the benefits of lifestyle interventions on cancer-related fatigue (CRF). Here, data on 321 cancer patients who took part in a phase III randomized controlled trial of a yoga intervention and reported both sleep quality and CRF were analyzed.

Compared with standard care alone, yoga was associated with significant improvements in both CRF and sleep quality (P < .01 for both), with a total reduction on the Multidimensional Fatigue Inventory of 6.5 points.

Further analysis indicated that 22% of the reduction in CRF associated with the yoga intervention was mediated by improving sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI). It was also found that 37% of the impact of yoga on CRF was mediated through the daytime dysfunction subscale of the PSQI.

Dr Oh: CRF is a significant issue for all patients with cancer. People have looked at various interventions to try to improve CRF, and what this study suggests is two things: One is that we don't really understand why patients with cancer and cancer survivors have so much fatigue, but sleep dysregulation is probably an important component of it; and that yoga improves fatigue, but it may do so, at least a quarter to a third of the effect, by just allowing patients and survivors to sleep better.

Dr Foxhall: Improvements in their measures of cancer-related fatigue as well as the quality of sleep were found, and there appeared to be some correlation between the two—in that yoga was improving sleep quality and that, in turn, may be contributing to improvements in fatigue.

That was interesting. There's certainly an opportunity to potentially give some guidance to patients who are having problems with CRF, which can be challenging to manage.

Colon Cancer Fatigue during Chemotherapy Reduced with Korean Red Ginseng

Abstract 10008 shifted the focus from exercise to diet. In this study, 438 patients with colorectal cancer at 15 institutions undergoing mFOLFOX-6 chemotherapy were randomly assigned to receive to Korean red ginseng 2000 mg/day or placebo for 16 weeks.

Compared with placebo, consumption of Korean red ginseng was associated with an improvement in global Brief Fatigue Inventory scores (78.54 vs 75.89; P = .0363) and usual fatigue scores (76.15 vs. 73.05; P = .0454).

There were also significant improvements in mood (P = .0086), relations with others (P = .0080), walking ability (P = .0090), and enjoyment of life (P = .0150), with ginseng consumption compared with placebo. There were no significant differences in toxicities between the two groups.

Dr Oh: It's hard for me to quantify exactly how much better the patients felt because the abstract doesn't really describe it very well, but basically what I would say is: This is a very well-conducted study, very carefully done, that seems to suggest that there's at least a statistically significant improvement in CRF with the use of Korean red ginseng.

The researchers also suggested that there were no significant side effects from this. It remains to be seen whether this type of approach could be more broadly used, because herbal therapies or natural products such as this may interact with other drugs, and we don't know enough about it yet to say that this should be done routinely during chemotherapy. But it is an encouraging study.

Dr Foxhall: It doesn't really say what stages of colorectal cancer the patients were in, but it appeared that there was some trend toward a reduction in fatigue, as measured by the Brief Fatigue Inventory, although it was of borderline significance. The investigators used another scale, a usual fatigue measure, which also showed some modest trends toward improvement and changes in mood. They don't really say which scale they used, but nonetheless, they assessed mood, and this improved at a fairly significant level. I'm not totally sure how clinically significant that change is, but there was a measured change.

There did not appear to be any significant toxicities associated with taking that dose of the drug, so they suggest that data support the benefits of consuming Korean red ginseng for fatigue. We should probably get some more information on whether or not this is something we would want to recommend to patients, but it's interesting at least. It showed some potential.

Psychological Interventions

Can Fear Be Conquered in Breast Cancer, Colorectal Cancer, and Melanoma Survivors?

One of the late-breaking abstracts presented at ASCO 2017, LBA10000 examined the effectiveness of Conquer Fear,—a psychological intervention comprising five sessions on attention training, detached mindfulness, challenging unhelpful metacognitions, value clarifications, and psychoeducation.

Disease-free survivors of stage I-III breast cancer, colorectal cancer, or melanoma were randomly assigned to receive the intervention (n = 121) or a relaxation training control (n = 101). The active intervention was associated with significantly greater reductions in Fear of Cancer Recurrence Inventory scores immediately after treatment (P < .001) and at 3- and 6-month follow-ups (P = .02 for both).

Dr Oh: As an oncologist, I know that patients are extremely anxious about the possibility that cancer may recur, even though they may potentially be cured. In some patients, this type of fear can be really debilitating.

I think this type of work suggests that we, as oncologists, don't pay enough attention to the psychological needs of our patients, even if they may be cured, because for some patients, anxiety and fear may be debilitating.

Dr Foxhall: The investigators said that 70% of people with cancer report significant fear, so it certainly is a common challenge for all patients. They showed a significant reduction in anxiety-related fear of recurrence with their intervention.

This is an evidence-based intervention, using psychological approaches to help address chronic fatigue. However, it's fairly intensive, with multiple counseling sessions that require trained counsellors to administer this over at least a 6-month period.

A CALM Approach to Managing Distress and Challenges in Advanced Cancer

Abstract LBA10001 reported on a study that examined a novel, brief, manualized psychotherapeutic intervention, Managing Cancer and Living Meaningfully (CALM), consisting of up to six sessions on symptom management and communication, recognizing changes in oneself and in relation to others, identifying meaning and purpose, and dealing with the future and mortality.

The researchers randomly assigned 305 patients with advanced cancer recruited from outpatient clinics to receive the CALM intervention or usual care. Compliance with the intervention was 77.5%. Those assigned to receive the CALM intervention reported significantly less severe depressive symptoms than those assigned to usual care at 3 months (P < .04) and at 6 months (P < .01).

The intervention was also associated with significant improvements in psychological well-being and preparation for the end of life at both time points compared with usual care.

Dr Oh: There was a high compliance rate. Patients were able to participate in the intervention, and the group that received the CALM training did significantly better in terms of depression and other signs of psychological well-being compared with the control group.

Again, this suggests that active interventions to reduce anxiety and stress in advanced cancer may help patients to manage their concerns about having advanced cancer.

Dr Foxhall: This study is about helping people with advanced cancer find better ways to cope with their situation, which is a significant challenge. The intervention appeared to have some benefits: People reported less problem with severe depression, and they reported less distress.

Again, it's multisession counseling, so it's hard to know how practical some of these are in a primary care setting, but nevertheless this and the previous study are certainly interesting opportunities to add some benefit to patients.

Tackling Distress in Newly Diagnosed Cancer With a Web-based Program

Finally, abstract LBA10002 looked at the distress associated with a new diagnosis of cancer, which is often accompanied by a lack of psychological support. The researchers conducted a prospective, wait-list controlled trial in which 128 patients recently diagnosed with cancer were randomly assigned to start an 8-week, web-based, modular minimal-contact stress management intervention either immediately or after a delay.

At baseline, 75% of participants reported a distress level greater than 4 on a 10-point scale. At week 8, compared with the wait-list control group, patients who started the intervention straight away had significantly higher quality of life on the Functional Assessment of Chronic Illness Therapy-Fatigue scale (P = .044) and a significantly lower distress score (P = .032).

There were no differences between the two groups in anxiety or depression scores on the Hospital Anxiety and Depression Scale at follow-up.

Dr Oh: In this category, the third approach looked at a web-based stress management tool. Now, we understand that very active interventions to treat distress may be very labor-intensive and expensive, so looking for simpler tools that are more convenient for both patients and providers could be valuable.

The study suggests that even a relatively simple online tool to manage patient stress at the diagnosis of cancer can improve quality of life and minimize stress.

Dr Foxhall: This intervention was delivered over the web, so there's potentially an opportunity for dissemination and broader use. The investigators showed, with an 8-week course, that they could deliver this, it was feasible to do, and it was effective in reducing distress.

This is a potentially useful opportunity to provide counseling for anxiety and stress reduction by using a web-based approach. This may be something that might be more accessible to a broader group in primary care.

Drs Oh and Foxhall have disclosed no relevant financial relationships.

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