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.     

Novel targeted strategies to overcome resistance in small-cell lung cancer: focus on PARP inhibitors and rovalpituzumab tesirine

Introduction: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumour, and its outcome is strongly conditioned by the rapid onset of resistance to conventional chemotherapeutics. First-line treatment with a combination of platinum agents and topoisomerase inhibitors has been the standard of care for over 30 years, with disappointing clinical outcome caused by early-acquired chemoresistance. In this disheartening scenario, novel treatment strategies are being implemented in order to either revert or bypass resistance mechanisms.

Areas covered: The general mechanism of action of the standard frontline treatment regimens for SCLC, as well as the known resistance mechanisms to these drugs, is reviewed. Moreover, we focus on the current preclinical and clinical evidence on the potential role of PARP inhibitors and rovalpituzumab tesirine (Rova-T) to tackle chemoresistance in SCLC.

Expert opinion: Preliminary evidence supports PARP inhibitors and Rova-T as two promising approaches to either revert or bypass chemoresistance in SCLC, respectively. The identification of potential predictive biomarkers of response to these innovative treatments (SLFN11 and DLL3) has shortened the gap between SCLC and personalized targeted therapy. Further large-scale clinical studies are urgently needed for a better designation of PARP inhibitors and Rova-T in the therapeutic algorithm of SCLC patients.     

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.     

Targeted and immuno-biology driven treatment strategies for triple-negative breast cancer: current knowledge and future perspectives

Introduction: Accounting for about 15% of breast cancer patients, triple-negative breast cancer (TNBC) is responsible for 25% of disease related deaths, more frequent distant spread and visceral metastasis. However, improving survival in TNBC failed and primary resistance, immunological ignorance and tumor heterogeneity limit clinical activity of novel therapies. In view of recent molecular, genetic and immunologic insights, this review aims to describe the current status of immunological and targeted treatments from a hypothesis driven perspective.

Areas covered: Recent preclinical studies and ongoing clinical trials for immune directed and targeted treatments of TNBC are summarized, including immune-checkpoint blockade, resistance mechanisms, inhibition of poly (ADP-ribose) polymerase (PARP), combinatorial strategies as well as preclinical, hypothesis generating studies.

Expert commentary: Sustained responses have been observed with immune-checkpoint blockade and PARP inhibitors demonstrated remarkable efficacy in germline BRCA mutated TNBC. In order to generate clinical success of many other, to date ineffective, targeted and immune therapies, the integration of multidimensional, large amounts of data, will be essential and likely accelerate treatment progress of TNBC.     

Exploiting DNA repair defects in breast cancer: from chemotherapy to immunotherapy

Introduction: Impaired DNA damage response (DDR) and subsequent genomic instability are associated with the carcinogenic process itself, but it also results in sensitivity of tumor cells to certain drugs and can be exploited to treat cancer by inducing deadly mutations or mitotic catastrophe. Exploiting DDR defects in breast cancer cells has been one of the main strategies in both conventional chemotherapy, targeted therapies, or immunotherapies.

Areas covered: In this review, the authors first discuss DDR mechanisms in healthy cells and DDR defects in breast cancer, then focus on current therapies and developments in the treatment of DDR-deficient breast cancer.

Expert opinion: Among conventional chemotherapeutics, platinum-based regimens, in particular, seem to be effective in DDR-deficient patients. PARP inhibitors represent one of the successful models of translational research in this area and clinical data showed high efficacy and reasonable toxicity with these agents in patients with breast cancer and BRCA mutation. Recent studies have underlined that some subtypes of breast cancer are highly immunogenic. Promising activity has been shown with immunotherapeutic agents, particularly in DDR-deficient breast cancers. Chemotherapeutics, DNA-repair pathway inhibitors, and immunotherapies might result in further improved outcomes in certain subsets of patients with breast cancer and DDR.     

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.     

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.     

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.     

Complicating “the good result”: narratives of colorectal cancer screening when cancer is not found

Objectives: In this paper, we analyze narratives from a Photovoice project on colorectal cancer screening that was carried out with people who had undergone screening and were found to not have cancer.

Methods: Three groups, totaling eighteen participants, took part in the project, meeting multiple times over the course of approximately 10 weeks, and discussing photos they took about colorectal cancer screening.

Results: A common way in which the participants conveyed their screening experiences was through reflection on their own or other people's illnesses. Our findings highlight the multiple meanings of receiving a “good” or noncancerous screening result after undergoing cancer screening.

Conclusion: Such findings suggest that framing noncancerous results only in terms of relief or other positive emotions may ignore the realities people and their families face and their remaining concerns. This paper has broader implications for policies to reduce cancer disparities as well as public health and patient-provider communication about screening.     

Cancer epigenetics and the potential of epigenetic drugs for treating solid tumors

Introduction: Epigenetic modification without DNA sequence mutation plays an important role in cancer development. Some small molecular inhibitors targeting key epigenetic molecules have been approved by the Food and Drug Administration to treat hematological malignancies. However, the anticancer effects of these drugs on solid tumors are not satisfactory, and the mechanisms of action remain largely unknown.

Areas covered: The review summarizes the latest research on cancer epigenetics and discusses the potentials and limitations of using epigenetic drugs to treat solid tumors. An analysis of possible reasons for epigenetic drug treatment failure in solid tumors in some clinical trials is discussed along with prospects for future development.

Expert commentary: Next-generation small molecule inhibitors will target novel epigenetic regulators with high cancer specificity. Combined modalities exploiting epigenetic drugs with chemo-/radiotherapy, molecular-targeting drugs, and immunotherapy will be able to effectively treat solid tumors in the near future.     

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.     

Immune checkpoint inhibitors: a new era for esophageal cancer

Introduction: The poor prognosis for patients with esophageal cancer (EC) requires evolving current treatment regimens. Immune checkpoint inhibitors show clinical efficacy and a great safety profile in multiple tumors. And the monoclonal antibodies that target programmed death receptor-1/programmed death receptor ligand-1 or the cytotoxic T lymphocyte antigen-4 pathway has shown potential curable effect of EC.

Areas covered: This review article covers the prognostic significance of immune checkpoint expression, the accumulating current clinical studies of checkpoint inhibitors in esophageal cancer patients, and future directions.

Expert opinion: Many clinical studies have reported favorable survival results with manageable toxicity of anti-programmed death receptor-1/programmed death receptor ligand-1 and anti-cytotoxic T lymphocyte antigen-4 treatment. More results are expected from future clinical studies. It is believed that combining chemoradiotherapy and immune checkpoint inhibitors can induce safe and efficient anti-tumor immune responses and can be a promising therapeutic strategy.     

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.     

Maternal stress and pediatric brain cancer: A French study

Background: Despite evidence that pediatric cancer induces a trajectory of parental stress, studies including mothers of children with malignant brain tumors remain scarce. The present work aims to add to the scientific literature by evaluating maternal stress with a French translation of the Pediatric Inventory for Parents (PIP) in a population of mothers whose children have been diagnosed with a brain tumor.

Procedure: The mothers of 35 children with malignant brain tumors completed the Pediatric Inventory for Parents (PIP), the State-Trait Anxiety Inventory (STAI) and the Family Assessment Device (FAD) at a mean time since diagnosis of 2.3 years.

Results: The PIP showed good internal consistency and correlated significantly with the STAI and the FAD. Maternal stress scores were higher in younger mothers and in mothers of younger children. Emotional functioning was the most affected domain.

Conclusions: Emotional stress as assessed by the PIP in mothers of children with malignant brain tumors is considerable, and should be routinely assessed, in order to implement appropriate specific psychosocial interventions when needed.     

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.     

Ixazomib promotes CHOP-dependent DR5 induction and apoptosis in colorectal cancer cells

Background: Ixazomib (Ninlaro), a novel proteasome inhibitor, has been developed for the treatment of many cancers and has demonstrated anti-tumor efficacy against various malignancies. However, the mechanism of the anti-tumor effect of ixazomib in colorectal cancer (CRC) cells remains unclear.

Methods: MTS and flow cytometry were performed to determine the effect of ixazomib on CRC cells. Western blotting and real-time RT-PCR were performed to detect ixazomib-induced DR5 upregulation. ChIP was performed to detect CHOP binding to DR5 promoter. Finally, xenograft experiments were carried out to measure the antitumor effect of ixazomib in vivo.

Results: In this study, we revealed the mechanism by which ixazomib inhibits the growth of CRC cells. Our findings indicated that ixazomib treatment induces CHOP-dependent DR5 induction, irrespective of p53 status. Furthermore, DR5 is necessary for ixazomib-mediated apoptosis. Ixazomib also synergized with TRAIL to induce marked apoptosis via DR5 in CRC cells.

Conclusions: Our findings further suggested that ixazomib sensitizes TRAIL/death receptor signaling pathway-targeted CRC and suggested that DR5 induction could be a valuable indicator of ixazomib sensitivity.     

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.     

Therapeutic potential of trametinib to inhibit the mutagenesis by inactivating the protein kinase pathway in non-small cell lung cancer

Introduction:Mitogen-activated protein kinase (MAPK) pathway is known to be involved in the tumorigenesis of cancer cells including non-small cell lung cancer (NSCLC) and kinases involved in this pathway are frequently mutated. The development of new targeted therapies in cancer has led to the evaluation of MEK-inhibitors.

Areas covered: This article reviews different studies using trametinib alone, in combination with other targeted therapies or associated with other non-targeted therapies in NSCLC, with a focus on KRAS mutant and BRAF mutant NSCLC.

Expert commentary: Trametinib demonstrated activity in association with a BRAF inhibitor when BRAF was mutated. The combination of trametinib and dabrafenib has been approved for this population of BRAF mutant NSCLC patients. For KRAS mutant NSCLC, the combination of trametinib with chemotherapy has showed promising results and should be further assessed. Several clinical trials are ongoing, assessing trametinib in combination with other targeted therapies. In addition, preclinical studies suggest a synergistic effect of trametinib in combination with immune checkpoint inhibitors and such combinations should be studied in clinical trials.