lung cancer patients

Depression Linked to Deadly Inflammation in Lung Cancer Patients

Posted by

0


Summary: Higher levels of inflammation linked to poorer survival rates are two to three times more likely in lung cancer patients with depression.

Source: Ohio State University

Lung cancer patients with moderate to severe depression are two to three times more likely to have inflammation levels that predict poor survival rates, a new study found.

The results may help explain why a substantial portion of lung cancer patients fail to respond to new immunotherapy and targeted treatments that have led to significantly longer survival for many people with the disease.

“These patients with high levels of depression are at much higher risk for poor outcomes,” said Barbara Andersen, one of the lead authors of the study and professor of psychology at The Ohio State University.

“Depression levels may be as important or even more important than other factors that have been associated with how people fare with lung cancer.”

The study was published online recently in the journal PLOS ONE.

Andersen and colleagues at Ohio State’s College of Medicine and The Ohio State University Comprehensive Cancer Center—Arthur G. James Cancer Hospital and Richard J. Solove Research Institute studied 186 patients who were newly diagnosed with advanced lung cancer (Stage IV). They were interested in how depression levels were related to systemic inflammation ratio (SIR) biomarker levels at diagnosis.

SIRs include three biomarkers associated with inflammation in the body. Higher inflammation is more dangerous and linked to lower survival rates.

All participants also completed a depression measure. The results showed that a large proportion of patients—35%—had moderate to severe depressive symptoms.

“Of all cancer patients, those with lung cancer are among those with the highest rates of depression, which makes the findings of our study even more concerning,” Andersen said.

Results showed an association between higher depression scores and higher inflammation scores, but the key finding was that patients with the highest depression levels were driving the relationship, Andersen said.

For example, take the platelet-to-lymphocyte ratio, one of the biomarkers in the study. For those with no or mild depression symptoms, 56% of patients were above the cutoff for dangerous levels of inflammation, versus 42% who were below.

But for those with high depression levels, 77% were above the cutoff for high levels of inflammation and only 23% were below.

“It was patients with high depression levels who had strikingly higher inflammation levels, and that is what really drove the correlation we saw,” she said.

These highly depressed patients were 1.3 to 3 times more likely to have high inflammation levels, even after controlling for other factors related to inflammation biomarker levels, including demographics and smoking status.

And analyses had shown that the baseline levels of all three biomarkers predicted overall survival. Specifically, patients with elevated neutrophil-to-lymphocyte ratios (one of the inflammatory biomarkers) were approximately twice as likely to die at any time point in the next two years compared to those with a lower inflammation ratio.

Andersen noted that this study measured the link between depression and inflammation when patients were first diagnosed, and as yet untreated.

But in a previous study by Andersen and her colleagues, they controlled for depression levels at diagnosis and found that the trajectory of continuing depression symptoms thereafter predicted survival. This was the first examination of the survival risk posed when depressive symptoms continue through treatment and thereafter.

This shows a depressed looking man
Higher inflammation is more dangerous and linked to lower survival rates.

The accumulating data suggest the importance of measuring and treating depression in patients with lung cancer, Andersen said.

She noted that there were more patients in this study with high depression/elevated inflammation than those having other indicators associated with poor survival in cancer patients: high school or lower education, overweight status, and a poor score on a test of ability to perform everyday activities.

Some doctors may think it is normal for cancer patients to be depressed, but that’s not true, she said.

“It is normal to be upset, sad and anxious about a cancer diagnosis, but it is not normal to have major depression,” Andersen said.

“Depression should not be discounted. This study shows the strong link between depression and inflammation, with both related to poor outcomes.”

Abstract

Depression in association with neutrophil-to-lymphocyte, platelet-to-lymphocyte, and advanced lung cancer inflammation index biomarkers predicting lung cancer survival

Lung cancer is a product of inflammation and a dysfunctional immune system, and depression has similar dysregulation. Depression disproportionately affects lung cancer patients, having the highest rates of all cancers.

Systemic inflammation and depression are both predictive of non-small cell lung cancer (NSCLC) survival, but the existence and extent of any co-occurrence is unknown. Studied is the association between systemic inflammation ratio (SIR) biomarker levels and patients’ depressive symptoms, with the hypothesis that depression severity would be significantly associated with prognostically poor inflammation.

Newly diagnosed stage-IV non-small cell lung cancer (NSCLC; N = 186) patients were enrolled (ClinicalTrials.gov Identifier: NCT03199651) and blood draws and depression self-reports (Patient Health Questionnaire-9) were obtained. For SIRs, cell counts of neutrophils (N), lymphocytes (L), and platelets (P) were abstracted for ratio (R) calculations for NLR, PLR, and the Advanced Lung cancer Inflammation Index (ALI). Patients were followed and biomarkers were tested as predictors of 2-year overall survival (OS) to confirm their relevance.

Next, multivariate linear regressions tested associations of depression with NLR, PLR, and ALI. Overall 2-year mortality was 61% (113/186). Cox model analyses confirmed higher NLR [hazard ratio (HR) = 1.91; p = 0.001] and PLR (HR = 2.08; p<0.001), along with lower ALI (HR = 0.53; p = 0.005), to be predictive of worse OS. Adjusting for covariates, depression was reliably associated with biomarker levels (p ≤ 0.02).

Patients with moderate/severe depressive symptoms were 2 to 3 times more likely to have prognostically poor biomarker levels. Novel data show patients’ depressive symptoms were reliably associated with lung-relevant systemic inflammation biomarkers, all assessed at diagnosis/pretreatment.

The same SIRs were found prognostic for patients’ 2-year OS. Intensive study of depression, combined with measures of cell biology and inflammation is needed to extend these findings to discover mechanisms of depression toxicity for NSCLC patients’ treatment responses and survival.

Yoga Offers Supportive Care for Lung Cancer Patients

Posted by

0


the pros and cons of exercise for lung cancer patients, Chinese researchers suggested that studies on physical activity in this patient population focus on methods such as Tai Chi and yoga.

Researchers at the University of Texas MD Anderson Cancer Center in Houston answered that call with a feasibility study of a dyadic yoga program for lung cancer patients and their caregivers, which was presented at the ASCO 2017 Palliative and Supportive Care in Oncology Symposium in San Diego.

 The Reading Room checked in with lead investigator Kathrin Milbury, PhD, on the results of the study, and also with physical therapist and yoga therapist Jaimie Perkunas, DPT, founder of Yoga is Therapy in Tucson, Arizona, on how lung cancer specialists can guide their patients to the appropriate yoga programs.

Partner Poses

Milbury’s group looked at the effects of their intervention on quality of life (QoL) and physical function versus a waitlist control group. Patients in the study had stage I-III non-small cell lung cancer (NSCLC), and were undergoing 25 fractions or more of intensity-modulated radiation therapy for 6 weeks.

“This program was particularly designed to address physical symptoms (e.g., dyspnea, fatigue) and psychological needs (e.g., distress, blame) common among lung cancer patients and their caregivers, a vulnerable yet understudied population,” the team wrote in a 2015 paper.

The dyadic yoga program was based on the Vivekananda yoga program. MD Anderson has an ongoing research collaboration with the Vivekananda Yoga Anusandhana Samsthana (VYASA), a yoga research foundation and university in Bangalore, India, Milbury noted.

 “The Vivekananda program allows us to tailor our yoga interventions to the type of cancer, so the program for the breast cancer patients is different than for the lung cancer patients. Some of the other yoga schools, like Iyengar, tend to be a bit more rigid, while other types of yoga are too fast moving. This program lets us adapt the sequence of physical postures to the patient populations’ needs.”

The yoga program consisted of 15, 60-minute sessions with four main components:

  • Joint loosening with mindfulness training
  • Physical postures (called asanas) paired with deep relaxation techniques
  • Breath work (called pranayama) with sound resonance
  • Meditation and guided imagery

“With these patients undergoing radiation, we wanted to focus on keeping the upper chest flexible,” Milbury said of the asana work. “We focused on a lot of chest-opening exercises to loosen up the muscles around the lungs. In general, there was more emphasis on stretching the upper body.”

As for the meditation and guided imagery, “we also focused on the needs of the population. Most of these patients are smokers, and with smoking-related etiology, there tends to be a lot of self-blame. So we focused on the idea of self-acceptance — compassion toward self and their partners.”

Sessions were jointly attended by the 26 pairs of patients and caregivers. The mean age of patients was 66.7, while the mean age of caregivers was 59.3. The vast majority of patients had stage IIIA and IIIB disease, with 57% having an ECOG status of 1.

 The dyads in the intervention group attended a mean of 12 sessions, with 65% attending a dozen or more. All participants rated components of the yoga program as very beneficial or beneficial, the researchers reported.

In terms of efficacy outcomes for the intervention, there was a statistically and clinically significant improvement for patients based on the 6 Minute Walk Test or 6MWT (478 m for the yoga mean versus 402 m for the control group (>70 m3, P<0.05).

The intervention patients also reported significant improvements in QoL domains, including physical function, stamina, and mental health (P<0.05), and clinically significant differences in symptoms at the end of radiotherapy, such as less distress, sadness, dyspnea, and fatigue, as well as better sleep.

One of the potential adverse events of radiotherapy in lung cancer patients is acute radiation pneumonitis, and the breathing techniques in the yoga program offered any benefits for patients who experienced symptoms such as breathlessness and cough.

“We found that the yoga intervention buffered against an increase in breathlessness,” Milbury said. “We weren’t able to eliminate this adverse event, but we were able to significantly buffer against it. Also, some patients experienced coughing, so we modified some of the yoga program components. For example, for some patients, lying flat on the ground in a supine position induced coughing, so we modified by propping their head up and so forth.”

As for the caregivers, “marginally to clinically significant” differences were seen in vitality (VT) and role performance (RP) versus waitlist controls, the authors noted. However, they pointed out that “based on dyadic analyses, [caregivers’] increase in VT and RP were significantly associated with patients’ 6MWT (P<0.01).”

While the randomized, controlled study was deemed feasible, study limitations included the racially homogenous sample (89% white patients; 100% white caregivers), the lack of a stringent control group, and the small sample size.

Milbury said the group is now in the process of seeking funding for an efficacy trial with a more stringent control group.

“We’ve known for some time that yoga can have a wide range of benefits for people who practice it,” commented Andrew S. Epstein, MD, of Memorial Sloan Kettering Cancer Center in New York City, a designated ASCO expert. “Ideally, the findings of this study will encourage people with advanced cancer and their caregivers to practice yoga.”

Into Practice

According to a 2014 Canadian study on yoga for health-related QoL, “patients across groups reported strong preferences for the following components of yoga: small class sizes, cancer-specific group, stretching, breathing practices, meditation, and physical postures for strength conditioning and restorative poses.”

While MD Anderson offers an in-house yoga program with classes that meet those criteria, many lung cancer patients will have to seek yoga outside their care facility. Given the incredible popularity of yoga – now estimated to be a $27 billion industry with more than 20 million practitioners in the U.S. alone — and the wide variety of yoga styles, how can lung cancer specialists best guide their patients to appropriate classes?

Milbury suggested that patients avoid yoga classes that contain the labels “power,” “hot,” or “flow,” as these will most likely be too vigorous for lung cancer patients. She also said patients may want to steer clear of gym-based classes versus those held at a dedicated yoga studio, as the latter will likely mean more individual attention. And she advised clinicians to emphasize that a patient should discuss the class style with the yoga teacher prior to attending.

Finally, “I’d recommend staying in the realm of gentle yoga,” she explained. “It’s also important that the yoga class focus on breathing exercises. Unfortunately in the West, a lot of the yoga classes are very focused on strengthening. That’s good to an extent, because lung cancer patients do experience deconditioning, so some strengthening is good, but the chest openers and breathing exercises have a lot of benefit for this population.”

Perkunas cautioned that sometimes classes called gentle can still be in the “flow” style, which consists of moving from one pose to the next fairly quickly. She advised directing patients to certified yoga therapists, through organizations such as the International Association of Yoga Therapists.

‘Yoga Therapy’ vs ‘Yoga’

What’s the difference between yoga therapy and yoga? As explained by yoga therapist Gary Kraftsow, writing in Yoga International, yoga therapy “fundamentally focuses on … clients’ needs. [A yoga therapist’s] job is to understand why their clients have come to see them and determine what they can do to support them … Therapists look for ways to help their clients reduce or manage their symptoms, improve their function, and help them with their attitude in relation to their health conditions … therapists choose yoga techniques in relation to how they will specifically benefit individual clients.”

Perkunas explained that when she has worked with lung cancer patients, they generally come to her post-treatment: “They are looking for a way regain a sense of trust with their bodies — to get back in touch with their bodies after this life-changing event.”

While she and the patients will often focus on asanas that promote chest opening, they will also look for ways to rebuild overall strength and mobility. But patients aren’t necessarily looking to improve QoL directly, Perkunas added.

“When I’ve worked with lung cancer patients, they are more interested in managing their physical symptoms — aches, pains. As a result of their ongoing [yoga] practice, they often notice they sleep better, they have less anxiety, they feel more relaxed. So these are benefits that come with a yoga practice, but they aren’t necessarily the person’s primary interest.”

Perkunas advised that clinicians focus more on yoga to regain strength and mindfulness: “Be careful not to set up expectations that yoga will fix or cure their symptoms. Yoga is not a cure-all, but it is an effective management tool for symptoms.”

Finally, Perkunas pointed out that yoga does have a spiritual and philosophical component to it that may not appeal to all patients. She suggested having patients experience a variety of yoga teachers to determine which style of teaching works best for them. Again, directing patients to a dedicated yoga therapy class may be the best option.

Of course, cost may be an issue as patients are likely to have to pay out-of-pocket. “I have people who call me and, after talking, we determine that I charge more than they are willing to pay,” Perkunas noted. “I’ll refer them to classes in the community, with teachers that I trust, that may be better for their budget. Asking around in your community is a route to finding an appropriate class.”

Statins Linked to Improved Lung Cancer Survival

Posted by

0


Mortality modestly lower for statin users in observational study..

Sustained statin use was associated with modestly better survival in lung cancer, an observational study in Great Britain showed.

People already on statins before diagnosis had a hazard ratio of 0.88 for lung cancer–specific mortality compared with other lung cancer patients after adjustment for various factors (P<0.001), Chris Cardwell, PhD, of Royal Victoria Hospital in Belfast, Ireland, and colleagues found.

Use after diagnosis was associated with a similar adjusted hazard ratio of 0.89 for lung cancer–specific mortality, albeit not statistically significant at P=0.09, the group reported in the May issue ofCancer Epidemiology, Biomarkers & Prevention.

That association was stronger after 12 prescriptions (adjusted HR 0.81, P=0.03) and when limited to lipophilic statins (adjusted HR 0.81, P=0.01), particularly simvastatin (Zocor), although attenuated in some sensitivity analyses.

Although these “associations could be causal or could reflect residual confounding or other biases,” the researchers pointed out “preclinical evidence for anticancer properties of statins from lung cancer cell lines and mouse models.”

Observational studies have also linked statins to better cancer-specific mortality in breast, prostate, and colorectal cancers.

“These results require confirmation in further large epidemiologic studies, particularly those with complete stage data, which could inform the decision to conduct a trial of simvastatin in lung cancer patients,” Cardwell’s group concluded.

Their study included 3,638 newly-diagnosed lung cancer patients in the English cancer registry from 1998 to 2009, linked to prescription records in the U.K. Clinical Practice Research Datalink and national mortality data up to 2012.

Decision-Making in Lung Cancer.

Posted by

0


TAKE-HOME MESSAGE

  • Adherence to treatment guidelines for lung cancer is estimated to range from 44% to 52%, with lower adherence for older patients and those with comorbidities. There is uncertainty regarding the benefit and toxicities of guideline treatments. Patients with lung cancer tend to have characteristics that may have been exclusion criteria for clinical trials (such as older age, comorbidities, or borderline performance status). Further research could help to define proper treatment of lung cancer to improve the applicability of the guidelines to the general population of lung cancer patients.
  • Further research to define the best treatments in the general lung cancer population would help to translate evidence from clinical trials into clinical practice.

ABSTRACT

Modelling demand for radiotherapy is contingent on the uniform application of clinical practice guidelines. However, decision making in lung cancer is a complex process requiring the integration of multimodality treatment in patients who frequently have underlying comorbidities. Population studies have shown that guideline adherence in lung cancer is modest, ranging from 44 to 52%. The application of guideline treatment decreases with increasing age and the presence of comorbidities. Patient and clinician attitudes also impact on this. In some regions, sociodemographic factors, such as lower income and non-White race, have been associated with a lack of guideline treatment. One of the major barriers in treating lung cancer patients according to guidelines is the mismatch between the clinic population and those enrolled in clinical trials from which evidence is derived. The lung cancer clinic population often consists of patients who are older, have multiple comorbidities and are of borderline performance status, all characteristics that are usually exclusion criteria for clinical trials. Hence, there is uncertainty not only about the magnitude of benefit, but also potential toxicities of guideline treatment. Further research is necessary in order to define the best treatment in these patients and thus increase the applicability of guidelines to the general lung cancer population. Lung cancer is an extreme example of the difficulties in translating evidence into clinical practice. The applicability of guidelines to specific cancer populations will affect the modelling of demand for radiotherapy and other treatment modalities.

 

Targeted drugs get first test in early stage lung cancer

Posted by

0


The National Cancer Institute (NCI) has launched an ambitious new nationwide clinical trial to find out if two molecularly targeted drugs that have improved outcomes in advanced lung cancer can increase survival of patients with early-stage lung cancer that has been surgically removed.

Dana-Farber Cancer Institute researchers Pasi Jänne, MD, PhD, director, Lowe Center for Thoracic Oncology at Dana-Farber, andGeoffrey Oxnard, MD, are leading the screening phase of the trial, in which some 6,000 to 8,000 patients will have their tumors tested for uncommon genetic alterations that are associated with improved response to targeted cancer drugs. Those who have the alterations will randomly receive either a targeted drug or a placebo, and all patients will be followed for five years to determine if the drug treatment prolongs survival.

One of the genetic alterations, in the EGFR gene, is found in about 10 percent of patients with adenocarcinoma of the lung, and 5 percent have an alteration in the ALK gene.

The opening of the clinical trial, called ALCHEMIST, was announced Monday by the NCI and by two NCI organizations that coordinate clinical trials. One is the Alliance for Clinical Trials in Oncology, and the other is the ECGG-ACRIN Cancer Research Group. ALCHEMIST is an acronym for the Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials.

Patients will be recruited at multiple centers across the country over the next five or six years. To be eligible, patients must already have had surgery to completely remove their lung tumors, and must have completed any adjuvant (follow-up) treatment such as chemotherapy and radiation. Samples of the removed tumor will be analyzed for the presence of EGFR and ALK mutations.

Patients found to have EGFR mutations in their tumors will be referred to a trial of the drug erlotinib (commercial name Tarceva®), while those with ALK mutations will enter a separate trial of treatment with crizotinib (Xalkori®). In each trial, patients will be randomized to the drug or a placebo. Trial leaders expect about 800 patients to receive a drug or placebo in the two treatment trials. All patients will be followed for five years, including the large number of patients who will be found to lack either mutation.

Although the Food and Drug Administration has approved erlotinib and crizotinib for treatment of advanced lung cancer, it’s not known whether the drugs will be effective in patients who have undergone complete removal of lung tumors with one of the mutations.

More than half of patients experience recurrences of lung cancer, even if it was completely removed, because tiny clumps of cancer cells invisible to the surgeon metastasize through the blood vessels to cause new cancers.

“We are excited to participate in this ambitious undertaking,” said Oxnard. “Through this large-scale collaborative effort to genotype thousands of early-stage lung cancer patients, ALCHEMIST allows us to test better adjuvant treatments while simultaneously teaching us important lessons about the genetic complexity of lung cancer.”

The trial will investigate, in addition to the potential survival benefit of the targeted drugs, each patient’s lung cancer risk characteristics, and will analyze tumor specimens when patients relapse to determine how their tumors become resistant to treatment.