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CHRONIC PPI USE INCREASE GASTRIC CANCER RISK

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Use of a proton-pump inhibitor (PPI) after Helicobacter pylori eradication more than doubles the risk for gastric cancer, according to a population-based study from Hong Kong.
The "clear dose-response and time-response" trend in PPI use and gastric cancer risk observed suggests the need for "caution when prescribing long-term PPIs to these patients even after successful eradication of H. pylori," write Wai Keung Leung, MBChB, MD, from Queen Mary Hospital, Hong Kong, and colleagues.
The study was published online October 31 in Gut.
The researchers point out, however, that this was an observational study, which can't prove cause and effect.
The new results also conflict with a recently published, US Food and Drug Administration–mandated follow-up study conducted with pantoprazole, said David A. Johnson, MD, chief of gastroenterology at Eastern Virginia Medical School in Norfolk (Aliment Pharmacol Ther2016;43:73-82).
"No increased risk [for gastric cancer] was observed with prolonged PPI exposure," he said.
Dr Johnson, who was asked for comment, also stated that the study has a "geographic bias" because it is from Hong Kong and "specific risks for gastric cancer are well recognized in Asian patients."
In the new study, Dr Leung and colleagues partly focused on H pylori infection and its relationship with gastric cancer.
H pylori eradication has been shown to reduce the risk for gastric cancer by 33% to 47%, but many patients develop gastric cancer even after eradication of H pylori. PPI therapy, "although generally considered safe," is associated with worsening gastric atrophy, particularly in H pylori–infected patients, the researchers point out. A recent meta-analysis found a 43% increased risk for gastric cancer among long-term PPI users, but it is was unable to adjust for H pylori, the major confounding factor.
Using a territory-wide health database in Hong Kong, Dr Leung and colleagues compared the risk for gastric cancer in PPI users and histamine-2 receptor antagonist (H2RA) users among 63,397 adults successfully treated with a 7-day course of triple therapy to eradicate H pylori between 2003 and 2012. 
"PPIs are much more potent than H2RA in terms of gastric acid suppression, and previous studies did not reveal any association between gastric cancer development and H2RA. Hence, H2RA was selected as a negative control exposure in our study," the researchers explain.
During a median follow-up of 7.6 years, 153 (0.24%) people developed gastric cancer after H pylori eradication therapy, mostly in noncardia regions (62%). None of the patients with gastric cancer tested positive for H pylori at diagnosis, but all had long-standing gastritis. The median age at cancer diagnosis was 71.4 years, and the median time from H pylori eradication to gastric cancer was 4.9 years.
After propensity score adjustment, people taking PPIs at least weekly had a greater than twofold increased risk for gastric cancer development (hazard ratio [HR], 2.44; 95% confidence interval [CI], 1.42 - 4.20). The propensity score–adjusted absolute risk difference between PPI use and non-PPI use was 4.29 excess gastric cancer cases per 10,000 person-years.
H2RA users had no increased risk (HR, 0.72; 95% CI, 0.48 - 1.07), which "further supports the specific role of PPIs on gastric cancer development," the researchers say.
After stratification by tumor site, PPI use was only significantly associated with an increased risk for noncardia gastric cancer (HR, 2.59; 95% CI, 1.42 - 4.72) but not cardia cancer (HR, 1.97; 95% CI, 0.57 - 6.82); "although this result should be interpreted with caution as this subgroup analysis has a relatively small number of cardia cancers," the researchers say.
Gastric cancer risk increased with longer duration of PPI use. The HR was 5.04 (95% CI, 1.23 - 20.61) for 1 year of use or longer, 6.65 (95% CI, 1.62 - 27.26) for 2 years of use or longer, and 8.34 (95% CI, 2.02 - 34.41) for 3 years use or longer.
More frequent use was also associated with greater risk. When compared with the reference group (less than weekly use), gastric cancer risk progressively increased with more frequent PPI use. The HR was 2.43 (95% CI, 1.37 - 4.31) for weekly to less than daily use, increasing to 4.55 (95% CI, 1.12 - 18.52) for daily PPI use.
The results remained significant by various sensitivity analyses.
A strength of the study is its use of data from a large population-based database with complete information on subsequent diagnoses and drug prescriptions, which minimizes selection, information, and recall biases, the researchers say. Use of strict exclusion criteria as well as propensity score adjustment to control for potential confounders and restricting the sample to patients with successful H pylorieradication are other strengths.
In terms of study weaknesses, the researchers  lacked information on some risk factors, such as diet, family history, and socioeconomic status.  And despite the large sample of more than 63,000 H pylori–infected patients, the small number of gastric cancer cases did not allow for any "meaningful evaluation of the dosage effect and role of different PPIs," the researchers say. 
The team also notes that PPIs users may have a higher chance of undergoing endoscopy than non-PPI users, leading to discovery of more gastric cancers due to surveillance bias.
Dr Johnson said there was another study weakness: "Important" demographic variables that are risk factors for gastric cancer — such as  smoking, alcohol use, obesity, diet, and family history — are not accounted for.  
He also made a general observation about PPI-related research: "Most studies showed that any potential effects of PPIs tend to disappear with time and that the most likely explanation for the effects is confounding by indication rather than causality."
Despite these limitations, Dr Leung and colleagues write that, to their knowledge, "this is the first study to demonstrate that long-term PPIs use, even after H. pylori eradication therapy, is still associated with an increased risk of gastric cancer. This is likely related to the profound acid suppression of PPIs that worsens atrophic gastritis, particularly in those patients with established gastric atrophy as a result of chronic H. pylori-induced inflammation."
EDITOR'S NOTE: The story has been updated to included comments from an expert not involved with the study.
The study had no specific funding. Dr Leung has received honorarium for attending advisory board meetings of Takeda and Abbott Laboratories. Dr Johnson has or has had financial ties to Pfizer Inc, which makes a PPI; Epigenomics; WebMD; CRH Medical; and Medtronic.

STATIN USE INCREASE DIABETES RISK

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Long-term statin use is associated with an increased risk of type 2 diabetes of approximately 30% in individuals at high risk of the disease, even after taking into account known risk factors and potential confounders, say US researchers.
They looked at the development of diabetes among statin users in the Diabetes Prevention Program (DPP), which included more than 3200 participants.
Over 10 years, statin use was linked to a 36% increased risk of being diagnosed with type 2 diabetes, falling to 27% after taking into account baseline risk factors and clinical criteria used to determine the need for statins.
The findings are consistent with previous studies suggesting that statin use substantially increases the risk of type 2 diabetes.
The new study was published online October 23 in BMJ Open Diabetes Research & Care by lead author Jill P Crandall, MD, department of medicine and diabetes research center, Albert Einstein College of Medicine, New York, New York, and colleagues.
As previously reported by Medscape Medical News, a study of more than 8700 Finnish men aged 45 to 73 years showed that over 6 years of statins therapy were linked to a 46% increased risk of type 2 diabetes — more than double prior estimates.
This was followed by recent data from the Australian Longitudinal Study on Women's Health, which indicated that, among almost 8400 women aged 76 to 82 years, the risk of new-onset diabetes ranged from 17% with the lowest statin doses to 51% with the highest doses.
Despite accumulating evidence, the current researchers still maintain that the overall healthcare advice remains unchanged — the benefits of statins outweigh the risks.
"For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment," they state.
They add: "Nonetheless, glucose status should be monitored and healthy lifestyle behaviors reinforced in high-risk patients who are prescribed statins for cardiovascular disease prophylaxis."

First Look at Diabetes Risk From Statins in High-Risk Patients

The researchers point out that the diabetogenic effect of statins has previously been studied in individuals typically at relatively low risk of diabetes and that the incidence of disease was based on self-report, rather than being the primary outcome.
They therefore set out to examine the issue in DPP participants, which included 3234 US adults randomized to intensive lifestyle intervention, metformin, or placebo.
After a mean follow-up of 3.2 years, participants were invited to take part in the DPP outcomes study, which included quarterly lifestyle sessions alongside open-label metformin for those originally randomized to the drug and two additional lifestyle programs per year for those originally randomized to the lifestyle intervention.
Approximately 50% of DPP participants were from ethnic groups and 20% were aged ≥ 60 years. To be included, they had to be aged ≥ 25 years and have a body mass index ≥ 24 kg/m2. They also had to have a fasting plasma glucose (FPG) of 95–125 mg/dL and impaired glucose tolerance, placing them at high risk of type 2 diabetes.
The primary end point was diabetes diagnosis using an annual 75-g oral glucose tolerance test or semiannual FPG level with repeat confirmation testing. Lipids and blood pressure were assessed annually and statin use was based on self-report.
From a baseline of approximately 4%, statin use progressively increased at the 10-year follow-up to reach 35% in the placebo group, 37% in the metformin group, and 33% in the lifestyle intervention group (P = .36 between groups).
Simvastatin was the most commonly used statin, taken by 40% of participants, followed by atorvastatin by 37% and, much less frequently, lovastatin and pravastatin, by 9% and 8%, respectively.
Statins users were typically older and more likely to be men than nonusers but did not differ by ethnicity. Compared with nonusers, they also had modestly higher baseline FPG and HbA1c, higher baseline low-density lipoprotein (LDL) cholesterol and triglycerides, and were more likely to have a history of cardiovascular disease and hypertension.
Taking into account age, sex, and ethnicity, researchers found that statin use was associated with a significantly increased risk of developing diabetes, at a hazard ratio (HR) of 1.36 for all three groups combined.
Further adjustment for baseline diabetes risk factors, including family history of diabetes and FPG, reduced the HR to 1.35, and additional adjustment for statin treatment confounders, such as blood pressure, cholesterol levels, baseline cardiovascular risk factors, and socioeconomic status, lowered the HR to 1.27.
Diabetes risk did not differ depending on statin potency or magnitude of LDL-cholesterol reduction, although longer statin use was significantly associated with greater diabetes risk (HR per visit with statin use, 1.06; P=.007).

Mechanisms Underlying Effect "Poorly Understood"

Discussing the findings, the researchers say that "it has been suggested that statins may 'uncover' diabetes in individuals at high risk, which on a population basis, could result in modest increase in diabetes risk."
They point out, however, that "variation in baseline diabetes risk factors failed to explain the further risk associated with statin therapy in our cohort, and the HR estimate was greatest among our lifestyle participants, who experienced the largest study-related reductions in diabetes risk."
The mechanisms underlying any diabetogenic effect of statins are "poorly understood," they add.
Although several studies have looked at changes in insulin sensitivity during statin use, "we saw no evidence of an effect of statins to modify insulin resistance, assessed as fasting insulin concentrations," they write.
And although statins have been reported to reduce pancreatic beta-cell insulin secretion in vitro, "the relevance to insulin secretion in vivo is not known," they state.
Taken together, evidence from studies published so far points to "an acceleration of typical glycemic deterioration, rather than a unique or statin-specific mechanism," they conclude.

LONG TERM RISK OF BREAST CANCER RECURRENCE

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LONG TERM RISK OF BREAST CANCER RECURRENCE

The risk of breast cancer returning continues long after the initial treatment has been completed. A new analysis shows that in the 20 years after initial diagnosis, there is an ongoing, steady risk of the cancer recurring in the form of deadly metastatic disease.
The absolute, cumulative risk for metastatic or distant recurrence among women with estrogen receptor–positive (ER+) breast cancer ranged from 10% to 41% over that time span, depending on various disease characteristics.
The findings about women with ER+ disease, which is the most common form of breast cancer, were published online November 8 in the New England Journal of Medicine.
The data come from a meta-analysis that included 88 clinical trials involving 62,923 women who were disease free after 5 years of scheduled endocrine therapy with tamoxifen or aromatase inhibitors.
Thus, all of the recurrences happened after that initial 5 years.
The women all had stage T1 (≤2 cm) or T2 (>2 cm to 5 cm) breast cancers (of varying grades) with fewer than 10 positive lymph nodes and no distant metastases. The patients were followed for up to 15 years after the 5-year treatment period, which generated 20-year data.
What is "surprising" about the findings is the "unrelenting risk over 20 years" and that metastases occur even among patients with the best prognoses, senior author Daniel Hayes, MD, of the University of Michigan Cancer Center in Ann Arbor, told Medscape Medical News.
The main aim of the study was to identify subgroups of patients for whom endocrine therapy could be stopped (thereby avoiding the side effects) after 5 years because their risk for long-term distant recurrence was "so small," say Dr Hayes and his international team of coauthors.
But they found that even among women with the least-threatening profile of small tumors (T1) who had no lymph node involvement (N0), there was a cumulative recurrence risk of 13% over a 20-year period. (The risk was 10% for the less aggressive, low-grade cancers; 13% for moderate-grade cancers; and 17% for high-grade.)
Notably, the annual rate of distant recurrence for these patients was about 1% for a period of 5 to 20 years (ie, after treatment ended), resulting in the 13% cumulative risk.
The new study "quantifies the 20-year risk more reliably than previous studies," owing to size, length of follow-up, and the quality of clinical trial-only evidence, say the authors.
The data "can help women and their health care professionals decide whether to extend therapy beyond 5 years and whether to persist if adverse events occur," they conclude.
An expert not involved with the study welcomed it but called attention to the concept of data reliability.
It is likely that the risk estimates presented in the paper do not completely apply to contemporary patients. Dr Lajos Pusztai
In short, some of the risks reported in the new study are probably higher than those seen currently, he suggested.
Nevertheless, Dr Pusztai agreed with the study authors that the major predictor of distant recurrence risk was status of the tumor stage and lymph node involvement at diagnosis.
Table 1. Distant Recurrence Risk to 20 Years
Stage at DiagnosisNodes InvolvedCumulative Risk
T1013%
 1 - 320%
 4 - 934%
T2019%
 1 - 326%
 4 - 941%
The main massage for me is that clinical stage matters. Dr Lajos Pusztai
The study authors state, "The risk of distant recurrence was strongly correlated with the original TN status." They also report that tumor grade and Ki-67 status were of only moderate independent predictive value for recurrence and that HER2 status was not predictive (however, only 2% of the women received trastuzumab).

Talking With Patients

Dr Pusztai said that the new data raise "a pressing clinical question: who are the patients who really need 10 years of endocrine treatment and who are cured with 5 years?"
He explained that several randomized clinical trials have demonstrated that 10 years of adjuvant antiestrogen therapy is more efficacious than 5 years of therapy. However, "the improvement is small, with 2% to 3% fewer distant recurrences, and the costs and potential side effects of taking a pill for 10 years are not negligible," he observed.
Useful" molecular diagnostic tests, including the Breast Cancer Index and the Prosigna assay, can now help identify patients who are both at risk for recurrence and remain endocrine sensitive and therefore benefit from extended endocrine therapy, he added.
Another expert who was approached for comment, Virginia Kaklamani, MD, of the Unitersity of Texas Health Science Center, San Antonio, said the new study "changes the conversation with patients.
"Extended endocrine therapy becomes an important part of the discussion, given the fact that [distant] recurrence after 5 years is higher than recurrence during the first 5 years," she told Medscape Medical News.
Extended endocrine therapy becomes an important part of the discussion. Dr Virginia Kaklamani
This is a reference to the fact that the study analyzed recurrence and disease-specific mortality risks in 5-year increments. And for each subgroup analysis, the same pattern was seen: a steady increase of associated risk over time, up to 20 years.
Steven Vogl, MD, a private practitioner in New York City, said the study was "good to have" and that he would look at it "again and again" with patients.
"What's nice about this paper is that they give you what you need to know ― the risk of distant metastases and death from breast cancer," he told Medscape Medical News.
He explained that breast cancer is only deadly once it spreads to distant vital organs.
Overall, the risk for breast cancer mortality "looks identical to distant recurrence except with lower percentages at each time point," summarized Dr Hayes.
Table 2. Cancer Mortality Risk to 20 Years
Stage at DiagnosisNodes InvolvedCumulative Risk
T107%
 1 - 313%
 4 - 922%
T2013%
 1 - 320%
 4 - 929%
The new meta-analysis has several limitations, including that it involved women who were scheduled to receive 5 years of endocrine therapy ― not who completed it. In six of the trials that investigated only tamoxifen, a "substantial minority" (11% to 31%) of women did not complete treatment.
That fact may lead to higher rates of recurrence risk in the study, just as 100% completion would lead to lower risk.
However, the authors also suspect that the rate of distant recurrence would have been 5% to 10% higher had the data not been tamped down by unreported breast-cancer events.
The team also could not "reliably assess" the relevance of chemotherapy to prognosis after the treatment period ended at 20 years. They acknowledged that the risk for recurrence after 5 years may be lower for women who receive contemporary chemotherapy compared to the risk for women in the study, echoing Dr Pusztai's comments.
The study was funded by Cancer Research UK, the British Heart Foundation, and the Medical Research Council at the University of Oxford. Dr Pusztai has worked with Biotheranostic to assess use of their Breast Cancer Index. Dr Hayes, and Dr Kaklamani, and Dr Vogl have disclosed no relevant financial relationships.

DISCUSSION FOR SEX WITH CANCER PATIENTS

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That is a question that a great many cancer patients would love to hear from their oncologists, but unfortunately, sexuality is not a topic that gets much attention.
A panel of experts here at the Palliative Care in Oncology Symposium (PCOS) 2017 tackled the subject of sex and the cancer patient and presented preliminary data demonstrating how "low-tech" interventions can make a dramatic difference for patients.
Sexuality is a somewhat taboo topic in oncology care, and perhaps even moreso in palliative care, explained panel member Anne Katz, PhD, RN, certified sexuality counselor at Cancer Care Manitoba, Canada. "But we know that this is important to patients and their partners across the cancer journey."
She cited a study (Psychooncology. 2011;21:594-601) that found that fewer than half (45%) of all cancer patients had a conversation with their healthcare provider about sex. By cancer type, 21% of lung cancer patients had such a conversation, as did 33% of breast cancer patients, 41% of colorectal cancer patients, and 80% of prostate cancer patients.
Men, it seems, get the "sex talk" a lot more frequently than women do.
According to Dr Katz, the "whole thing is skewed" by prostate cancer. More than twice as many men speak to their providers about sex as compared to women.
"If we didn't talk about nausea, if we didn't talk about constipation, we would be regarded as negligent, even indulging in malpractice," Dr Katz pointed out. "Yet we are leaving out conversations about this very important quality-of-life issue, which persists into end-of-life care.
"Sexuality is much more than just intercourse. It is about touch and intimacy and about much more than what we do in the bedroom," she said.
A recent study (J Cancer Surviv. 2017 Apr;11:175-188) again showed that a "preponderance" of men (60%) had a discussion about sex with their provider, whereas fewer than half as many women did (28%).
However, healthcare providers thought "they were doing a good job," with almost 90% reporting that they were. "So there is a very large gap as to who is saying what and who is hearing what," explained Dr Katz.
Another problem is that the cancer patient is much more likely to raise the topic with their provider, rather than the reverse. This is a problem, she pointed out, "because in every other area, we raise the topic with our patients, indicating that its important. By not opening the door, by not starting the conversation, we are saying to our patients that 'this is not important and I don't want to talk about it.' "
Panelist Sharon Bober, PhD, founder and director of the Sexual Health Program at the Dana-Farber Cancer Institute in Boston, Massachusetts, agreed with that summation. "We have to expand our perspective on what sexuality is, in the context of serious illness and palliative care. It's too easy to be reductionist and think about whether some can or cannot have sex - this isn't what it's about."
We have to expand our perspective on what sexuality is, in the context of serious illness and palliative care. Dr Sharon Bober
Sexuality, she noted, is a human experience across the lifespan. It's a multidimensional experience that involves physiology, behavior, emotion, cognition, and identity.
"What we can take from some of the qualitative and survey work that's been done to date is that expressions of sexuality can be a vital aspect of providing comfort and relieving suffering, maintaining connections in the face of life-limiting illness, and affirming a sense of self when other roles are lost," Dr Bober explained. "When sexually is not made part of care, there is an implicit message that is it no longer important and/or the challenges cannot be addressed."
Unfortunately, providers often took a medicalized approach, as was evidenced in one study (Contemp Nurse. 2007 Dec;27:49-60). Patient sexuality and intimacy were largely medicalized; the discussion remained at the level of patient fertility, contraception, and erectile or menopausal status, Dr Katz noted.
"There is a lot of active avoidance," she said. She pointed out that the "patient reports the topic and the oncologist takes three steps back and flies out the door."
The oncologist takes three steps back and flies out the door. Dr Anne Katz
Some of the reasons given for not discussing sexuality were reactions of colleagues, fear of litigation, and fear of misinterpretation.
The topic needs to be brought up in the context of quality of life, she emphasized, "but we need to open the door."
There is the fear of not knowing what to say, but there is "Dr Google, there are books, there are experts, and if you don't know, you will find the resources to refer patients to them," Dr Katz said. "We have a responsibility to discuss sexual side effects of cancer treatment."

Very Brief but Very Effective

Sexual function is profoundly disrupted by gynecologic cancer treatment, and 90% of patients with ovarian cancer report distressing changes in sexual function. "The good news is that ovarian cancer patients are living longer, and almost 50% of survivors will live many years post diagnosis," explained Dr Bober. "But they often have to endure multiple surgeries and multiple rounds of chemotherapy, and sexuality and distress are generally not addressed."
She pointed out that with ovarian cancer patients, "no one talks about this. The thought Is often that you have bigger fish to fry, you may not live anyway ― there are all kinds of reasons that this doesn't get addressed."
Dr Bober described an intervention that they devised at Dana Faber to address sexual dysfunction in ovarian cancer survivors. Not only was it brief, easily accessible, and "doable" by patients, but final results showed that it was quite effective.
The format was integrative. It was composed of a single half-day group intervention with a didactic teaching and experiential exercises, coupled with an individualized action plan. After the session was completed, the participants were asked to reflect on what was pertinent to them and what they were going to work on during the next 6 weeks.
The session was followed by a brief telephone call, in which the action plan was reviewed and additional support was offered if needed, to uncover additional challenges that needed to be addressed.
Because this was a pilot study, it did not include a control group per se, Dr Bober explained, but participants served as their own controls. This was accomplished by having a 2-month run-in period, during which women filled out surveys at baseline then waited for 2 months before completing the survey a second time before beginning the intervention. The purpose of the 2-month run-in period was to estimate changes in symptoms that could not be attributed to the intervention.
The design comprised three modules. Module 1 was targeted on sexual health education, which discussed vaginal health, enhancing arousal, and increasing low desire. Module 2 involved body awareness and relaxation training, in which participants learned pelvic floor education, progressive muscle relaxation, and body scan. Module 3 involved a mindfulness-based cognitive training, which sought to increase nonjudging awareness of automatic thoughts, with progression from avoidance/distraction to acceptance.
The cohort included 46 women with stage I-IV ovarian cancer who reported at least one distressing sexual symptom. The mean time since diagnosis was 6.3 years (range, 1 - 20 years). "Twenty years is a very long time to be dealing with distressing sexual problems," emphasized Dr Bober.
Within this group, 13% were currently receiving chemotherapy, and 44% were currently taking medication for anxiety, depression, or pain.
In evaluating the program, 97% of the women found the it helpful, 100% found it easy to understand, and 95% found the it enjoyable.
With regard to helping sexual functioning, "There were no changes during the run-in period, for the most part, demonstrating that time alone did not change the situation," said Dr Bober. "But at month 2 after the interactions, there was significant improvement over multiple domains of sexual function. And for the most part it held over to 6 months."
Although the pilot study was not focused on mental health per se, there was significantly less psychological distress observed in the participants, especially regarding symptoms of depression and distress.
It was a small pilot study, she emphasized, but the implications are that brief sexual health rehabilitation in the context of serious illness is effective. "There was meaningful improvement in sexual function and emotional distress, and improvements at 6 months."
Dr Bober emphasized that there is an enormous need for evidence-based intervention research, with interventions conducted outside of an academic center in order to reach more people. "There is a need for identify optimal methods for delivery," she said. "In some of the palliative care literature, patients talk about struggling with this issue within 2 to 3 months before they die, so this is not something that is relevant only if you're well."

Pilot Study in Transplant Patients

Similar to other oncology settings, sexual dysfunction is a common long-term complication for survivors of allogeneic hematopoietic stem cell transplant (HCT), but it is rarely discussed, and interventions to enhance sexual function in this population are lacking.
The preliminary efficacy of a multimodal intervention designed to improve sexual function in allogeneic HCT survivors was very encouraging, reported Areej El-Jawahri, MD, instructor of medicine at Harvard Medical School and director of the Bone Marrow Transplant Survivorship Program at the Massachusetts General Hospital, Boston.
Dr El-Jawahri and her colleagues conducted a pilot study to assess the feasibility and preliminary efficacy of the intervention in a cohort of 50 patients. The participants were at least 3 months' post transplant and had screened positive for distress caused by sexual dysfunction.
"There was a very wide age range, from 24 years to 75 years," she said. "The median time from HCT at enrollment was 29 months, but there was also a wide range between 3 and 173 months."
The primary endpoint of the study was feasibility: 75% of patients who screened positive would agree to participate and attend the first visit, and at least 80% would attend at least two intervention visits.
The majority of patients had acute leukemia (55%), and nearly 64% had chronic graft vs host disease (GVHD).
The format consisted of monthly intervention visits with trained study clinicians. The visits focused on assessing sexual dysfunction, educating and empowering patients to address this topic, and implementing therapeutic interventions that targeted their specific needs.
The PROMIS Sexual Function and Satisfaction Measure, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), and Hospital Anxiety and Depression Scale (HADS) were used to assess sexual function, quality of life (QOL), and mood at baseline and 6 months post intervention.
The study met its primary endpoint of feasibility; 94% (47/50) agreed to participate, and 100% of this group attended at least two interventions. The median number of visits were two (range, two to five). The median duration of the first visit was 50 min; for the second visit, it was 30 min. In addition, 28% (13/47) had a partner attend an intervention visit.
Results were encouraging, Dr El-Jawahri pointed out. "Sexual activity in the group increased."
Before the intervention, 32.6% of patients reported not engaging in any sexual activity; that number declined to 6.5% after the intervention.
In men, the following therapies were implemented: phosphodiesterase inhibitors (PDI) on demand (57%), psychoeducation (52%), penile constriction rings (48%), referral to a sexual health clinic (9%), daily PDI treatment (4%), topical GVHD treatment (4%), and hormone replacement therapy (4%).
For women, therapies included vaginal estrogen (67%), dilator (63%), lubricant (58%), psychoeducation (42%), topical GVHD treatment (42%), topical lidocaine (8%), and referral to a sexual health clinic (4%).
"All outcomes were clinically and statistically significant," said Dr El-Jawahri.
Table.
OutcomesPreintervention (%)Postintervention (%)P Value
Global satisfaction with sex16.0729.70<.0001
Interest in sex10.9815.39<.0001
Orgasm2.194.22<.0001
Vaginal discomfort33.7714.92.0005
Vaginal lubrication19.4434.310
Erectile functioning19.5832.74<.0001
The program was efficacious in improving QOL and mood.
"This has very promising efficacy, but we need to conduct a randomized clinical trial, and there is a need to asses longer-term outcomes," Dr El-Jawahri concluded. "It also has potential for adaptation to other types of cancer survivors as clinicians to deliver this kind of intervention and allow for dissemination."
Dr El-Jawahri's study was funded by the National Comprehensive Cancer Network and the Patty Brisben Foundation. Dr Bober has a relationship with Apexo Neuro; Dr Katz and Dr El-Jawahri have disclosed no relevant financial relationships. 
Palliative Care in Oncology Symposium (PCOS) 2017. Panel and abstract 191 (Dr El-Jawahri), presented October 28, 2017.

GENE SIGNATURES IN BREAST CANCER

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Results of a 70-gene signature assay (70-GS) can influence recommendations about adjuvant treatment for patients with early breast cancer classified as intermediate risk by a 21-gene assay (21-GA), researchers say.
“The use of genomic assays in early stage ER-positive, HER2-negative breast cancer has become a standard practice for determining who should get adjuvant chemotherapy,” Dr. Hatem Soliman of Moffitt Cancer Center in Tampa, Florida, told Reuters Health.
“There are still some situations where the initial genomic test doesn't provide a clear answer. In these cases, the provider and patient may require additional information - almost like a second opinion - to guide them,” he said by email.
“However,” he added, “this is costly and should be done only in cases where the clinicopathologic information and initial genomic test are equivocal.”
To investigate, Dr. Soliman and colleagues enrolled 840 patients (mean age, 59; 87% white) with early-stage breast cancer and a 21-gene assay recurrence score of 18 to 30 (intermediate risk). All patients also were classified with the 70-GS, and results were given to physicians before adjuvant treatment was started.
As reported in JAMA Oncology, online October 26, on the basis of 21-GA result (before 70-GS assessment), 382 patients (45.5%) were recommended to receive adjuvant chemotherapy and 458 (54.5%) were recommended not to receive it.
The 70-GS reclassified the intermediate-risk patients as low-risk in 374 cases (44.5%) and high-risk in 466 cases (55.5%).
Receiving the 70-GS classifications significantly influenced adjuvant treatment assessment. Among the low-risk patients, 108 (28.9%) had chemotherapy removed from their treatment recommendation, whereas 171 (36.7%) high-risk patients had chemotherapy added.
The 70-GS results were significantly associated with the physician’s adjuvant treatment recommendation: 88% of high-risk patients were recommended to receive adjuvant chemotherapy, and 91% of low-risk patients were recommended not to receive it.
After receiving the 70-GS results, physicians reported having greater confidence in their treatment recommendation in 79% of cases.
Dr. Soliman said, “The information provided by the 70-GS assay had a significant clinical impact on adjuvant therapy recommendations. So in cases where there is initial uncertainty regarding the use of adjuvant chemotherapy, the 70-GS assay can aid in identifying patients with an excellent prognosis using endocrine therapy alone.”
Experts in cancer genetics weighed in on the findings in emails to Reuters Health.
Dr. Sofia Merajver, Scientific Director of the Breast Cancer Program and Director of the Breast and Ovarian Cancer Risk Evaluation Program at the UM Comprehensive Cancer Center in Ann Arbor said, “It is unknown whether survival would be improved by the change in therapy for those patients, and that is the gold standard.”
“Plus, the total expression of proteins is not sufficient to define the signaling processes inside cells, nor is a single static measure robust enough to predict long-term survival or time to recurrence, the outcome variables patients are truly interested in,” she observed.
“In essence, this paper just proves what doctors and patients are willing to do. The hope is that the value of adjusting the therapy was not overstated during this research, since so much (outcomes) data still needs to be collected.”
Dr. Dana Zakalik, Director of the Beaumont Cancer Genetics Program at Beaumont Hospital in Royal Oak, Michigan, commented, “The 70-gene assay seems to ‘simplify’ the genomic risk score into two categories (high vs. low) and addresses the uncertainty of the ‘intermediate’ risk score of the 21-gene assay, for which we still await data.”
“We need more data and validation to answer whether this is a better assay or whether it merely simplified it by just having a high versus a low group,” he added.
“There has not been a head-to-head comparison between the different assays, so we need more research and longer follow-up. Hopefully,” he said, “we will soon have data on the ‘intermediate’ group of the 21-gene assay, and perhaps that will resolve some questions.”
Dr. Glenn Gerhard, Chair of the Department of Medical Genetics and Molecular Biochemistry at Temple University in Philadelphia said, “Risk stratification for breast cancer for the significant number of patients classified as intermediate risk by the 21-GA assay is problematic; thus, other approaches are needed.”
“More comprehensive genomic testing using the 70-GS assay provides important additional information in a setting in which physicians use limited clinical data and other more traditional information to guide decision making,” he added.
Like Dr. Merajver, Dr. Gerhard noted that “recurrence and survival data were not collected as part of the study; thus, whether the changes in treatment decisions altered outcomes has not yet been determined.”
“The results were also restricted to patients with ER-positive, HER2-negative cancers, to those with a designated range of 21-GA results, and to a largely white population,” noted. “Thus, the extent of generalizability is not known.”
The study was sponsored by Agendia, a molecular diagnostics company that employs four of the authors.