Longitudinal associations of plasma metabolites with persistent fatigue among colorectal cancer survivors up to 2 years after treatment

The underlying biological mechanisms causing persistent fatigue complaints after colorectal cancer treatment need further investigation. We investigated longitudinal associations of circulating concentrations of 138 metabolites with total fatigue and subdomains of fatigue between 6 weeks and 2 years after colorectal cancer treatment. Among stage I-III colorectal cancer survivors (n = 252), blood samples were obtained at 6 weeks, and 6, 12 and 24 months posttreatment. Total fatigue and fatigue subdomains were measured using a validated questionnaire. Tandem mass spectrometry was applied to measure metabolite concentrations (BIOCRATES AbsoluteIDQp180 kit). Confounder-adjusted longitudinal associations were analyzed using linear mixed models, with false discovery rate (FDR) correction. We assessed interindividual (between-participant differences) and intraindividual longitudinal associations (within-participant changes over time). In the overall longitudinal analysis, statistically significant associations were observed for 12, 32, 17 and three metabolites with total fatigue and the subscales “fatigue severity,” “reduced motivation” and “reduced activity,” respectively. Specifically, higher concentrations of several amino acids, lysophosphatidylcholines, diacylphosphatidylcholines, acyl-alkylphosphatidylcholines and sphingomyelins were associated with less fatigue, while higher concentrations of acylcarnitines were associated with more fatigue. For “fatigue severity,” associations appeared mainly driven by intraindividual associations, while for “reduced motivation” stronger interindividual associations were found. We observed longitudinal associations of several metabolites with total fatigue and fatigue subscales, and that intraindividual changes in metabolites over time were associated with fatigue severity. These findings point toward inflammation and an impaired energy metabolism due to mitochondrial dysfunction as underlying mechanisms. Mechanistic studies are necessary to determine whether these metabolites could be targets for intervention.     

A mixed method study of medical oncologists’ perceived barriers and motivators to addressing long-term effects in breast cancer survivors

Breast Cancer Research and Treatment - The purpose of this study was to identify oncologist-reported barriers and motivators in addressing long-term effects with breast cancer survivors. This study...     

Learning and memory performance in breast cancer survivors 2 to 6 years post-treatment: the role of encoding versus forgetting

Purpose

Our previous retrospective analysis of clinically referred breast cancer survivors’ performance on learning and memory measures found a primary weakness in initial encoding of information into working memory with intact retention and recall of this same information at a delay. This suggests that survivors may misinterpret cognitive lapses as being due to forgetting when, in actuality, they were not able to properly encode this information at the time of initial exposure. Our objective in this study was to replicate and extend this pattern of performance to a research sample to increase the generalizability of this finding in a sample in which subjects were not clinically referred for cognitive issues.

Methods

We contrasted learning and memory performance between breast cancer survivors on endocrine therapy 2 to 6 years post-treatment with age- and education-matched healthy controls. We then stratified lower- and higher-performing breast cancer survivors to examine specific patterns of learning and memory performance. Contrasts were generated for four aggregate visual and verbal memory variables from the California Verbal Learning Test-2 (CVLT-2) and the Brown Location Test (BLT): Single-trial Learning: Trial 1 performance, Multiple-trial Learning: Trial 5 performance, Delayed Recall: Long-delay Recall performance, and Memory Errors: False-positive errors.

Results

As predicted, breast cancer survivors’ performance as a whole was significantly lower on Single-trial Learning than the healthy control group but exhibited no significant difference in Delayed Recall. In the secondary analysis contrasting lower- and higher-performing survivors on cognitive measures, the same pattern of lower Single-trial Learning performance was exhibited in both groups, with the additional finding of significantly weaker Multiple-trial Learning performance in the lower-performing breast cancer group and intact Delayed Recall performance in both groups.

Conclusions

As with our earlier finding of weaker initial encoding with intact recall in a cohort of clinically referred breast cancer survivors, our results indicate this same profile in a research sample of breast cancer survivors. Further, when the breast cancer group was stratified by lower and higher performance, both groups exhibited significantly lower performance on initial encoding, with more pronounced encoding weakness in the lower-performing group. As in our previous research, survivors did not lose successfully encoded information over longer delays, either in the lower- or higher-performing group, again arguing against memory decay in survivors. The finding of weaker initial encoding of information together with intact delayed recall in survivors points to specific treatment interventions in rehabilitation of cognitive dysfunction.

Implications for Cancer Survivors

The finding of weaker initial encoding of information together with intact delayed recall in survivors points to specific treatment interventions in rehabilitation of cognitive dysfunction and is discussed.

     

Are the effects of cognitive behavior therapy for severe fatigue in cancer survivors sustained up to 14 years after therapy?

Purpose

Cognitive behavior therapy (CBT) reduces cancer-related fatigue (CRF) in cancer survivors in the short term. We examined fatigue levels up to 14 years after CBT.

Methods

Eligible participants of two randomized controlled trials who had completed CBT for CRF and a post-treatment assessment were contacted (n?=?81). Fatigue was assessed with the subscale “fatigue severity” of the Checklist Individual Strength (CIS-fatigue). The course of fatigue over time was examined with linear mixed model analyses. Fatigue levels of participants were compared to matched population controls at long-term follow-up. We tested with multiple regression analysis if fatigue at follow-up was predicted by the patients’ fatigue level and fatigue-perpetuating factors directly after CBT (post-CBT).

Results

Seventy-eight persons completed a follow-up assessment (response rate?=?96%, mean time after CBT?=?10 years). The mean level of fatigue increased from 23.7 (SD?=?11.1) at post-CBT to 34.4 (SD?=?12.4) at follow-up (p?<?0.001). Population controls (M?=?23,9, SD?=?11.4) reported lower fatigue levels than participants. Half of the patients (52%) who were recovered from severe fatigue at post-CBT (CIS-fatigue <?35) were still recovered at long-term follow-up. Patients with lower fatigue levels at post-CBT were less likely to show relapse.

Conclusion

Despite initial improvement after CBT, levels of fatigue deteriorated over time. Half of the patients who were recovered from severe fatigue after CBT still scored within normal ranges of fatigue at long-term follow-up.

Implications for Cancer Survivors

It should be explored how to help patients with a relapse of severe fatigue following an initially successful CBT. They may profit from CBT again, or another evidence-based intervention for fatigue (like mindfulness or exercise therapy). Future research to gain insight into reasons for relapse is warranted.

     

Are survivorship care plans responsive to African-American breast cancer survivors?: voices of survivors and advocates

Purpose

African-American breast cancer survivors (AABCS) suffer the greatest from cancer recurrence, morbidity, and mortality in part due to the lack of cancer follow-up care and surveillance. To improve survival and survivorship, the Institute of Medicine advises that cancer survivors be provided a survivorship care plan (SCP). The current study investigated AABCS’ understanding of SCP and gathered preliminary feedback on infusing cultural and socioecological responsiveness.

Methods

The study embraced a community-based participatory research framework. Three facilitated, structured, consensus meetings were conducted with AABCS (N?=?25) and advocates (N?=?3) to provide information towards identifying the content domains of an SCP that are culturally responsive to AABCS.

Results

AABCS recommended inclusion of patient-centered information on the purpose and use of the SCP. They raised concerns that higher mortality in AABCS may be due to greater comorbidities and inadequate surveillance and follow-up care. Participants recommended that the SCP document all comorbidities and medications, regardless of relationship to cancer; referrals for cancer-related providers; and culturally informed health advisories.

Conclusion

Study findings indicate that the available SCP template lacked adequate content on health history, comorbidity, health promotion, and functioning. These factors constitute the underlying clinical, psychosocial, and behavioral risks for poor disease outcomes that may be exacerbated in AABCS.

Implications for Cancer Survivors

SCPs are intended to educate and activate patients to join their oncology care team as informed partners. However, the emerging science and implementation of SCPs seem void of patient input. Our investigation suggests a practical approach for survivor engagement in the SCP discourse to increase their cultural responsiveness and patient-centeredness.     

Long-term survivors of childhood cancer: cure and care—the Erice Statement (2006) revised after 10 years (2016)

Purpose

The number of persons who have successfully completed treatment for a cancer diagnosed during childhood and who have entered adulthood is increasing over time, and former patients will become aging citizens.

Methods

Ten years ago, an expert panel met in Erice, Italy, to produce a set of principles concerning the cure and care of survivors of childhood and adolescent cancer. The result was the Erice Statement (Haupt et al. Eur J Cancer 43(12):1778–80, 2007) that was translated into nine languages. Ten years on, it was timely to review, and possibly revise, the Erice Statement in view of the changes in paediatric oncology and the number and results of international follow-up studies conducted during the intervening years.

Results

The long-term goal of the cure and care of a child with cancer is that he/she becomes a resilient and autonomous adult with optimal health-related quality of life, accepted in society at the same level as his/her age peers. “Cure” refers to cure from the original cancer, regardless of any potential for, or presence of, remaining disabilities or side effects of treatment. The care of a child with cancer should include complete and honest information for parents and the child.

Conclusions and implication for cancer survivors

Some members of the previous expert panel, as well as new invited experts, met again in Erice to review the Erice Statement, producing a revised version including update and integration of each of the ten points. In addition, a declaration has been prepared, by the Childhood Cancer International Survivors Network in Dublin on October 2016 (see Annex 1).

     

Ependymoma in children under the age of 3 years: a report from the Canadian Pediatric Brain Tumour Consortium

The determination of optimal therapy for ependymoma (EP) in infants is ongoing. We describe the incidence, management and outcomes of Canadian infants with EP to discern potential future research questions. Of 579 cases registered in a national database of children <36 months of age diagnosed with a brain tumor from 1990 to 2005, inclusive, 75 (13 %) were EP. These cases were analyzed. A mean annual age-adjusted incidence rate of 4.6 per 100,000 children years was calculated. The male:female ratio was 1.77. Of the tumors, 80 % were infratentorial in location, 67 % were WHO grade II histology, and 29 % were metastatic at diagnosis. All patients underwent a surgical procedure. A complete resection of the tumor was achieved in 56 % of the cases; 43 % of these patients survive while 36 % of the patients with tumors less than completely resected survive. Initial therapy consisted of surgery alone in 23 % of patients, or surgery plus chemotherapy (37 %), radiation therapy (RT; 19 %), or both (21 %). Any use of RT increased with patient age. The 5-year EFS rates for patients in each of the four treatment groups was 22, 11.5, 46.2 and 64.8 %, respectively. For all patients the median survival was 63 ± 6 months and 5-year overall survival was 55 ± 6 %. Patients treated with surgery and chemotherapy alone were younger and had a lower rate of survival than older patients who were more often treated with radiation therapy containing regimens. Further study is needed to determine which patients are optimally served with these treatment modalities.     

Employment experience of cancer survivors 2?years post-diagnosis in the Study of Cancer Survivors-I

Introduction  

A large percentage of cancer survivors are in the workforce and it is important to understand their experiences and challenges in the workplace and work status changes.     

Quality of life among long-term (⩾5 years) colorectal cancer survivors – Systematic review

BackgroundDue to the growing number of long-term (?5 years) colorectal cancer survivors, investigation of their quality of life (QoL) is important for an evaluation of chronic or late effects of the disease and treatment and to adjust treatment strategies to patients’ needs.MethodTo summarise current research results, multiple databases including PubMed, EMBASE and CINAHL were used to identify articles about long-term QoL of colorectal cancer survivors. The content of 10 included studies was independently extracted by two reviewers.ResultsColorectal cancer survivors indicated a good overall QoL, but may have slightly lower physical QoL than the general population. Furthermore, survivors had worse depression scores and reported to suffer from long-term symptoms such as bowel problems and distress regarding cancer. Apart from stoma and recurrence of the disease, mainly general and health-related factors such as age, social network size, income, education, BMI and number of comorbidities were associated with QoL. Studies were mainly conducted in the United States (US) (n = 7) and were heterogeneous with respect to the QoL instrument used and the adjustment to covariates. QoL assessment was cross-sectional in all studies.ConclusionDespite an overall good QoL, colorectal cancer survivors have specific physical and psychological problems. The reported determinants of QoL may serve to identify survivors with special needs. But further studies are needed that focus on problems like distress, depression and bowel problems of long-term colorectal cancer survivors.     

Sexual health problems in French cancer survivors 2 years after diagnosis—the national VICAN survey

Purpose

The purpose of this study is to assess French cancer survivors’ sexual health 2 years after diagnosis.

Methods

Using the French National Health Insurance System database, the representative national VICAN survey was created comprising 4349 adults (12 cancer sites), still alive 2 years after diagnosis and aged 18–52 (“younger”) or 53–82 (“older”). Sexual health was evaluated using six items from the Relationship and Sexuality Scale, and an overall indicator was created.

Results

Among the study’s 1955 sexually active participants, 18.6 % (versus 13.1 %), 39.8 % (versus 39.9 %) and 29.4 % (versus 29.8 %) of men (versus women) were affected, respectively, by “strong”, “moderate” and “weak” sexual health deterioration, while 12.2 % (versus 17.1 %) were spared sexual problems (P?=?0.001). Strong deterioration more often concerned older men with prostate (27.7 %) and lung (26.1 %) cancers, younger men with upper aero-digestive tract cancers (25.2 %) and women (younger/older) with cervical cancer (24.2 %). Substantial (strong/moderate) sexual health deterioration was observed for all cancer sites, rates ranging from 68.3 % (prostate) to 37.2 % (melanoma). In all four gender/age subgroups, increasing age predicted poorer sexual health, although statistical significance was not reached in older women. Apart from genital cancer, perceived consequences, such as general sequelae and fatigue, were the primary factors associated with severe sexual problems.

Conclusions

Two years after diagnosis, the majority of sexually active French cancer survivors reported impaired sexual health. Younger and older men and women with cancer in non-reproductive sites also reported problems.

Implications for Cancer Survivors

Interventions aimed at improving sexual health irrespective of age and cancer site should be developed.

     

Anti-Müllerian hormone screening to assess ovarian reserve among female survivors of childhood cancer

Purpose

Anti-Müllerian hormone (AMH) is an indicator of oocyte reserve in healthy females. The role of AMH testing in oncology remains investigational, although its sensitivity and stability over the menstrual cycle make it an attractive screening test for fertility assessment among female cancer survivors. We measured AMH level in survivors of childhood cancer and evaluated its association with treatment and patient factors.

Methods

Participants were adult female survivors of childhood malignancy treated with chemotherapy. Serum AMH was measured at a random day of the menstrual cycle. Multivariate analysis was used to evaluate the association between AMH level, alkylating agent exposure using the cyclophosphamide equivalent dose (CED), and other covariates.

Results

Sixty-six females with a median attained age of 23.3 years were eligible for analysis. Median AMH was 25.5 pM (range 0.5–108.0), at a median time of 11.5 years (range 1.4–25.1) since cancer diagnosis. Twenty-three patients (34.8 %) had low AMH, including a significant proportion that reported normal menstrual cycles. Compared to ALL survivors, sarcoma survivors had significantly lower AMH levels. Among alkylating agents evaluated, procarbazine had the greatest adverse effect on AMH. In multivariate analysis, higher CED (p?=?0.001), older age at diagnosis (p?p?=?0.04) remained significantly associated with lower AMH.

Conclusions

Random AMH can reveal evidence of oocyte depletion among female survivors reporting normal cycles, although low AMH should be interpreted cautiously among those taking oral contraception. Age at exposure and CED can aid identification of those more likely to have low AMH, although CED may underestimate the effect of procarbazine on oocyte reserve.

Implications for cancer survivors

Measurement of AMH can reveal apparent depletion of ovarian reserve in female childhood cancer survivors reporting normal menstrual cycles. Sarcoma survivors and those exposed to procarbazine may benefit from targeted AMH evaluation in an outpatient setting, and thereby allow appropriate fertility counseling before the onset of premature ovarian failure. The cyclophosphamide equivalent dose may facilitate comparison of the potential effect of different regimens on fertility.