Prostate cancer: the influence of stigma on quality of life and relationship satisfaction for survivors and their partners

Objectives: Prostate cancer (PCa) stigma and its relationship to quality of life (QoL) is a relatively new finding. As the experiences of couples facing PCa are shared, the study examined the relationship between of PCa stigma, QoL, and relationship satisfaction of PCa survivors and their spouses.

Design: A correlational design with dyadic data was used.

Sample: Participants (N?=?80 dyads) were PCa survivors and their spouses sampled from an oncology center and PCa support groups.

Methods: Structural equation modeling was used to assess how stigma related to the QoL and relationship satisfaction of participants.

Findings: Stigma had a negative association with QoL, but not relationship satisfaction. There were no significant demographic differences in regards to stigma.

Conclusion: Overall, stigma has a relationship with the experience of couples, but not with every aspect of their experience.

Implications for psychosocial providers: Implications for clinicians in regards to addressing PCa stigma with clients and areas for future research are discussed.     

Benefits,challenges, and needs of people living with cancer and their companion dogs: An exploratory study

Purpose/Objectives: The study examined whether the bond with a companion dog is associated with well-being among people with cancer, and described the perceived benefits, challenges, and needs accompanying the relationship with the dog.

Design: The design was cross-sectional.

Sample: Participants were 140 people recently diagnosed with cancer with at least one dog in their household.

Methods: The online survey included measures of the human–pet bond, depressive symptoms, positive affect, and health-related quality of life, as well as open-ended questions about the experience of having a dog since being diagnosed with cancer.

Findings: Although the bond with a companion dog was not directly linked with well-being, the association between the human–pet bond and depressive symptoms depended in part on treatment status.

Conclusions: Companion dogs may play an important role in the lives of people recently diagnosed with cancer.

Implications for psychosocial providers: Health care providers can help to support the bond with a companion dog.     

Family dynamics in young adult cancer caregiving: “It should be teamwork”

Purpose/Objectives: Young adult cancer patients undergo stress at a time when their primary source of psychosocial support may be changing. Our goal was to provide insight into the expectations young adult patients and their family caregivers for types of psychosocial support.

Research Approach: Semi-structured interviews.

Participants: Fifteen patients, 9 caregivers recruited from an AYA clinic.

Methodological Approach: Thematic content analysis using the constant comparison method.

Findings: Two themes were identified. First, families described coordinating support around strengths to determine who would take on caregiving roles/tasks. Second, families described the importance of patient-caregiver relationship status/history in determining trust and expectations.

Interpretation: Family strengths and existing relationships can impact caregiving roles and expectations for families of young adult cancer patients.

Implications for Psychosocial Providers: Cancer clinics may need to involve members of the psychosocial provider team to better understand the family dynamics of their patients and how these relate to support.     

Prevalence of psychosocial distress in cancer patients across 55 North American cancer centers

Routine distress screening in United States oncology clinics has been mandatory since 2015.

Objective: This study was the first to assess distress in a geographically diverse sample of cancer patients following mandated distress screening implementation by oncology social workers.

Methods: Sites were self-selected via social workers who applied to participate in the Association of Oncology Social Work’s Project to Assure Quality Cancer Care, advertised through their social media outlets and conference. Electronic screening records were collected from 55 cancer treatment centers in the United States and Canada. Cases required cancer diagnoses and Distress Thermometer (DT) scores to be included. Distress rates and rates by age, sex, cancer type, and ethnicity were examined.

Results: Of 4664 cases, 46% (2157) experienced significant distress (DT score?≥?4). Being female, age 40-59, and having diagnoses of pancreatic or lung cancer was associated with increased likelihood of distress. Half of cases experience clinically-significant distress, though this need was not evenly distributed across patient or cancer types.

Conclusion: Identifying those at risk for distress may help inform optimal resource allocation. Methods to address needs of distressed patients in cases of limited resources are discussed.     

Proteomic and bioinformatic analysis of condyloma acuminata: mild hyperthermia treatment reveals compromised HPV infectivity of keratinocytes via regulation of metabolism,differentiation and anti-viral responses

Background: Hyperthermia has proved successful in treating cutaneous human papillomavirus infectious diseases such as plantar wart and condyloma acuminata (CA). Moreover, this treatment provides improved therapeutic efficacy in these conditions as compared with conventional therapies.

Objectives: To investigate the global proteome changes in CA in response to hyperthermia and achieve a better understanding of the mechanisms of hyperthermia therapy against HPV-infectious diseases.

Methods: CA tissue was obtained from patients undergoing pathological examinations. Diagnosis was verified as based on results of both HE staining and HPV-DNA PCR assay. Hyperthermia was achieved with a 44?°C water bath. Differentially expressed proteins (DEPs) were identified by iTRAQ labeling, SCX chromatography and LC-MS/MS assay. Validation of proteomic results was performed using real-time qPCR and western blot, while bioinformatic analysis of DEPs was accomplished by R 3.4.1, STRING and Cytoscape softwares.

Results: In response to hyperthermia, a total of 102 DEPs were identified with 37 being upregulated and 65 downregulated. Among these DEPs, hyperthermia induced proteins involved with anti-viral processes such as OAS1, MX1, BANF1, CANX and AP1S1, whereas it inhibited proteins that participated in cellular metabolism, such as GALT, H6PD, EXOSC4 and EXOSC6; protein translation, such as RPS4Y1; as well as keratinocyte differentiation, such as KRT5, KRT27, KRT75, KRT76 and H2AFY2.

Conclusions: Hyperthermia inhibited enzymes and molecules responsible for metabolism modulation and keratinocyte differentiation in CA tissue, whereas it promoted factors involved in anti-viral responses. Such effects may, in part, contribute to the efficacy of local hyperthermia therapy against HPV infection.     

Microwave ablation of hyperplastic parathyroid glands is a treatment option for end-stage renal disease patients ineligible for surgical resection

Background: Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD). Some patients with severe SHPT could not be managed by medical treatment and are ineligible for surgical resection.

Purpose: Our objective was to evaluate the efficacy, safety of microwave ablation (MWA) on these patients.

Materials and Methods: Between 1 April 2015 and 28 February 2017, 35 patients (M/F 19/16, age 49.8?±?12.9?years) were enrolled. All patients were treated with MWA. Levels of intact parathyroid hormone (iPTH) and of serum calcium and phosphorus were compared pre- and post-ablation. Repeated-measures ANOVA was used to compare treatment outcomes pre- and post-ablation.

Results: Complete ablation was achieved in all 63 glands in the 35 patients with SHPT. The mean follow-up time was 15.9?±?2.2?months. The maximum gland diameter was 6–31?mm (mean, 14.9?±?5.5?mm). The trends of the changes in iPTH and calcium levels showed a curve: the level of iPTH and calcium at 6?months post-ablation were lower than those pre-ablation (both p?<?.0001); after then iPTH remained relatively stable and the end of follow up, with no rebound (p?<?.0001), while instead of calcium at the end of follow up was not significantly lower than pre-ablation (p?=?.462). The trend in the change in phosphate levels showed a straight line; the level of phosphate at 6?months post-ablation and at the end of follow up both were significantly lower than pre-MWA (p?<?.001). There was no major complication.

Conclusions: In this series, MWA was used successfully to treat SHPT patients who are ineligible for surgical resection.     

Goal disturbance in early-stage breast cancer survivors

Purpose: Cancer-related goal disturbance can influence long-term outcomes in cancer patients and survivors; however, few studies have examined the factors that contribute to goal disturbance in early survivorship.

Design: The current study examined the relationships between demographic variables, cancer- and treatment-related factors, and behavioral and psychological symptoms (i.e., fatigue, pain, cognitive complaints, depressive symptoms, and anxiety) and goal disturbance in breast cancer survivors 1?year after treatment completion.

Methods: Women diagnosed with early-stage breast cancer (n?=?171) completed assessments following primary treatment (i.e., surgery, radiation, and chemotherapy) and again 6?months and 1?year later. We focused on the 1-year post-treatment assessment when participants were asked if they had experienced a cancer-related goal disturbance.

Findings: Approximately, 27% of women reported a cancer-related goal disturbance. Analyses indicated that both receipt of chemotherapy and behavioral and psychological symptoms—analyzed as a composite score and individually—were associated with a higher probability of reporting a goal disturbance.

Conclusions: Chemotherapy and behavioral and psychological symptoms were unique correlates of goal disturbance, suggesting that the impact of chemotherapy extends beyond its influence on persistent symptoms.

Implications: Elucidating factors that inhibit the pursuit of meaningful activities in early survivorship is critically important to understanding the long-term psychosocial impacts of cancer diagnosis and treatment.     

Starvation in cancer cells: circulating arginine is good for cancer but bad for patients

Introduction: Currently, basic understanding of heterogeneity and complexity of tumors is depicted at molecular, cellular, genetic, epigenetic and metabolic adaptations levels.

Areas covered: There are appreciable numbers of views to pinpoint signaling axis that support metabolic adaptations of cancer cells in response to environmental pressures including nutritional factors and drug treatments. Specifically, nutritional deprivation and autophagy in certain types of cancer are linked to the abilities of cancer cells to use arginine in an auxotrophic or prototrophic manner.

Expert opinion: Hence, this paper highlights the current scope of arginine- and autophagy-centered metabolic adaptations across tumor types and possible avenues to bring tumors towards cytotoxic or cytostatic death.     

Mental health comorbidities and cost/utilization outcomes in head and neck cancer patients

Purpose: Examine the relationship between mental health comorbidities and health services outcomes in non-elderly adults with head and neck cancer (HNC).

Design: Retrospective, cross-sectional.

Sample: Non-elderly adults with a primary diagnosis of HNC in U.S. Department of Defense (TRICARE) administrative claims data for fiscal years (FY) 2007–2014.

Methods: Linear regression and generalized linear models were used to examine predictors of reimbursed cost and healthcare utilization, respectively.

Findings: On average, there were 2944 HNC patients each year, the majority age 55–64, male, military retirees or family members of retirees, cared for in civilian facilities, and residing in the U.S. southern region. Between FY2007 and FY2014, there were slight increases in prevalence rates for diagnosed depression (12.4%–13.1%), anxiety (8.2%–11.9%), adjustment disorders (3.7%–5.8%), and drug use disorders (10.3%–19.4%), and a slight decrease in alcohol use disorders (12.3%–11.4%). In the cost regression model, depression and anxiety were the seventh and eighth strongest predictors (p?<?.001), behind hospice use, treatment modalities, chronic physical conditions, and tobacco use. In the utilization regression models, depression, adjustment disorder, and anxiety ranked seventh, ninth, and eleventh as the strongest predictors for the number of ambulatory visits; anxiety, depression and substance use disorder ranked fifth, sixth, and eighth in the model examining predictors of the number of annual hospitalizations; and anxiety and depression ranked fifth and sixth in the model examining predictors of the annual number of bed days.

Conclusions: We found strong evidence that mental health comorbidities impact cost and utilization among HNC patients, independent of other factors.

Implications for Psychosocial Providers or Policy: Addressing mental health comorbidities among HNC patients may reduce cost and improve resource efficiency.     

Predicting social withdrawal,anxiety and depression symptoms in pediatric brain tumor survivors

Objective: Pediatric brain tumor survivors (PBTSs) are at risk for impairments in social adjustment and psychological distress. This study investigated longitudinal associations between symptoms of social withdrawal and anxiety/depression in PBTS, as well as medical, demographic, and personal characteristics that may also influence reports of social withdrawal and anxiety/depression.

Method: About 91 PBTS (51% male, mean age 11.21?years, off-treatment) participated. At baseline and 8?months follow-up, primary caregivers of PBTS completed measures of social withdrawal, anxiety, and depression symptoms. Medical information (e.g. tumor type and location, cranial irradiation therapy) and child personal characteristics (e.g. child’s age and gender, executive function, social skills) were obtained at baseline.

Results: Baseline reports of depression symptoms and social skills predicted social withdrawal 8?months later. Social withdrawal at baseline predicted greater combined anxiety and depression symptoms 8?months later. Depression alone predicted greater anxiety symptoms at follow-up. Anxiety symptoms and poor global executive functioning predicted greater depression symptoms at follow-up.

Conclusions: The social adjustment and psychological distress of PBTSs are interrelated and can influence each other across time. These findings support the importance of multifaceted interventions targeting both psychological distress and social adjustment, in order to support the optimal psychosocial adjustment of PBTSs.     

The impact of epidermal growth factor receptor mutations on the efficacy of definitive chemoradiotherapy in patients with locally advanced unresectable stage III non-small cell lung cancer: a systematic review and meta-analysis

Objectives: To investigate the impact of EGFR mutations on the efficacy of definitive chemoradiotherapy (CRT) in patients with locally advanced unresectable stage III NSCLC.

Methods: PubMed and EMBASE were searched for eligible studies. Efficacy outcomes included objective response rate (ORR), overall disease progression, local-regional recurrence (LRR), distant progression (DP), brain metastasis, progression-free survival (PFS) and overall survival (OS). Meta-analysis was performed when relevant data were available.

Results: The authors identified seven eligible studies including 695 patients. No significant difference was detected in ORR (Risk Ratio [RR] 1.13, 95% confidence interval [CI] 0.91–1.39, P = 0.28) and overall disease progression (RR 1.06, 95% CI 0.95–1.19, P = 0.29) between EGFR-mutant and EGFR-wild-type groups. EGFR-mutant group had significantly lower LRR (RR 0.49, 95% CI 0.33–0.72, P < 0.01), higher DP (RR 1.36, 95% CI 1.18–1.55, P < 0.01) and higher brain metastasis (RR 2.48, 95% CI 1.46–4.20, P < 0.01) than the EGFR-wild-type group. No sufficient data were available to perform pooled analysis regarding PFS and OS.

Conclusion: For patients with locally advanced unresectable stage III NSCLC treated with definitive CRT, the presence of EGFR mutations may be indicative of lower locoregional recurrence and higher distant progression, especially brain metastasis.     

Emotions and coping methods of Turkish parents of children with cancer

Objective: This hermeneutic phenomenological study was conducted with the aim to determine the emotions and coping methods of Turkish parents whose children were diagnosed with cancer.

Methods: Data were collected through in-person, in-depth interviews with 12 parents (8 mothers, 4 fathers). The semi-structured interview form was developed based on Elisabeth Kübler-Ross's model of the five stages of grief (denial, anger, bargaining, depression and acceptance) with the addition of questions on coping methods.

Data interpretation proceeded through three phases: superficial reading, structural analysis and comprehensive understanding.

Results: All the parents made statements indicating their devastation while expressing their feelings at the moment they learned of the diagnosis. After overcoming the first shock, most thought it was a false diagnosis, and some thought it was a test from God. The parents were angry mostly with the doctors, themselves, their spouses and God. All the parents participating in the study stated that they had regrets about the past. Most engaged in more emotion-oriented and fewer problem-focused coping efforts. However, some parents used negative coping methods.

Conclusion: These parents need help from healthcare professionals to come to terms with their grief.     

Larotrectinib for the treatment of TRK fusion solid tumors

Introduction: TRK fusions occur across a wide range of cancers in children and adults. These fusions drive constitutive expression and ligand-independent activation of the TRK kinase and are oncogenic. Larotrectinib is the first highly potent and selective small molecule ATP competitive inhibitor of all three TRK kinases to enter clinical development.

Areas covered: This review covers the current preclinical and clinical evidence for TRK inhibitors for TRK fusion cancers, focusing on larotrectinib.

Expert commentary: Larotrectinib has demonstrated a remarkable 75% centrally confirmed objective response rate in patients with TRK fusion cancers in phase 1 and phase 2 clinical trials with generally mild side effects. Responses appear independent of the patient’s age, underlying histology, and specific fusion partner and are durable in many patients. Larotrectinib is likely to be the first FDA-approved histology-agnostic molecularly targeted therapy. The evolving role of molecular profiling of advanced cancers is discussed.     

Decision-making,knowledge, and psychosocial outcomes in pediatric siblings identified to donate hematopoietic stem cells

Purpose: To (a) describe the decision-making experience and psychosocial outcome of sibling hematopoietic stem cell (HSC) donors, and (b) to determine the feasibility of completing a prospective and longitudinal assessment of HSC sibling donors at a single institution.

Design: A mixed-methods approach was utilized.

Sample and methods: 12 potential siblings HSC donors aged 10–21?years completed various psychological measures and participated in semi-structured interviews at three time points in the donation experience: pre-donation, within 1?week after the harvest procedure, and six months post-donation. Caregivers also completed parent-proxy measures.

Findings: Qualitative analysis indicated donors want to make their own decision about donation but may not be given the option or may feel that there is no choice given their limited awareness of alternative options. Donors felt well prepared for the donation procedure but demonstrated a poor understanding of possible recipient outcomes. A minority of donors endorsed emotional distress prior to and after donation; however, this was not linked to recipient health. Forty percent of donors felt that they had inadequate support following their donation. Small sample size restricted quantitative data analysis.

Conclusions and implications: Utilizing a donor advocate offers opportunity to work with donors to encourage decision-making tied to ideals rather obligation, increase education about possible recipient outcomes, and offer support at key times, such as when a recipient dies. Future research should include prospective multi-site studies.     

Addressing the psychosocial needs of cancer patients: a retrospective analysis of a distress screening and management protocol in clinical care

Background: A growing recognition of the impact of distress on the quality of life and adherence to treatment of cancer patients has been documented. As a result, national guidelines and standards of care mandate providers to implement distress screening protocols to connect patients with psychosocial services. However, limited literature has examined whether distressed patients are referred to care and their needs addressed. This article assessed differences in rates of referral and psychosocial services by demographic factors, clinical characteristics, and distress severity. Potential predictors of these two outcomes were investigated.

Methods: A retrospective analysis of patient data abstracted from electronic medical records of a NCI-designated Academic Comprehensive Cancer Center was conducted. Of the 399 cases meeting the inclusion criteria, 302 (75.7%) were screened for distress with the Distress Thermometer. Differences were examined with chi-square, t-tests, and ANOVAs. Predictors were identified with multivariate logistic regressions.

Results: Overall, patients who were identified as distressed were referred to a psychosocial provider (71.4%) and psychosocial services were delivered in approximately 64% of the cases. Referrals and service delivery rates varied by age group, clinic, health insurance coverage, distress severity, and presence of psychosocial issues. Only the distress score predicted the likelihood of being referred, and of a provider intervention to occur.

Conclusions and implications for psychosocial providers: Although the protocol appeared to facilitate referral and service delivery to patients scoring above the cutoff for distress, our results suggest that patients were more likely to not have their distress and psychosocial needs addressed if they were older, without insurance coverage, and were seen in clinics where a social worker was not consistently available. Future studies able to monitor patient outcomes in terms of quality of life, satisfaction with care, and service utilization are recommended.     

Reactivation of heat-inactivated Ku proteins by heat shock cognate protein HSC73

Purpose: Mouse double-stranded DNA-dependent protein kinase (DNA-PK) activity is heat sensitive. Recovery of heat-inactivated DNA repair activity is a problem after combination therapy with radiation and heat. We investigated the mechanism of recovery of heat-inactivated DNA-PK activity.

Methods: Hybrid cells containing a fragment of human chromosome 8 in scid cells (RD13B2) were used. DNA-PK activity was measured by an in vitro assay. Immunoprecipitation of the nuclear extract was performed with an anti-Ku80 antibody. Proteins co-precipitated with Ku80 were separated by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis and detected by Western blotting using anti-heat shock protein (HSP)72 and anti-heat shock cognate protein (HSC)73 antibodies. HSC73 was overexpressed with the pcDNA3.1 vector. Short hairpin (sh)RNA was used to downregulate HSC73 and HSP72.

Results: The activity of heat-inactivated DNA-PK recovered to about 50% of control during an additional incubation at 37?°C after heat treatment at 44?°C for 15?min in the presence of cycloheximide (which inhibits de novo protein synthesis). Maximal recovery was observed within 3?h of incubation at 37?°C after heat treatment. Constitutively expressed HSC73, which folds newly synthesized proteins, reached maximal levels 3?h after heat treatment using a co-immunoprecipitation assay with the Ku80 protein. Inhibiting HSC73, but not HSP72, expression with shRNA decreased the recovery of DNA-PK activity after heat treatment.

Conclusions: These results suggest that de novo protein synthesis is unnecessary for recovery of some heat-inactivated DNA-PK. Rather, it might be reactivated by the molecular chaperone activity of HSC73, but not HSP72.     

Unique genomic profiles obtained from cerebrospinal fluid cell-free DNA of non-small cell lung cancer patients with leptomeningeal metastases

Background: Leptomeningeal metastases (LM), associated with poor prognosis, are frequent complications of advanced non-small cell lung cancer (NSCLC) patients, especially in patients with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the mutational landscape of LM has not been comprehensively investigated in large cohorts and the underlining biology of LM remains elusive. Some studies have explored the potential of cerebrospinal fluid (CSF) in reflecting the molecular profile of LM but with limited number of patients enrolled.

Methods: In this study, we performed capture-based targeted sequencing using a panel consisting of 168 lung cancer-related genes on matched CSF and plasma samples from 72 advanced NSCLC patients with confirmed LM to interrogate the potential of CSF as a source of liquid biopsy.

Results: We revealed a rate of detection of 81.5% and 62.5% for CSF and plasma, respectively (p = 0.008). The maximum allelic fraction (MaxAF) was also significantly higher in CSF (43.6% vs. 4.6%) (p < 0.001). CSF, harboring a unique genomic profile by having a significant number of CSF-specific mutations, primarily copy number variations, is superior to plasma in reflecting the mutational profile of LM. Further pathway enrichment analysis revealed that most of CSF-specific mutations participated in pathways relevant to the tumorigenesis and the development of metastases. Moreover, our data also revealed that TP53 loss of heterozygosity (LOH) predominantly existed in CSF (p < 0.001).

Conclusions: Collectively, we demonstrated that CSF provides a more comprehensive profile of LM than plasma in a large cohort, thus can be used as an alternative source of liquid biopsy for LM patients.