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 in the room: common emotional reactions to discussions of poor prognosis and tools to address them

Introduction: Advanced cancer patients often want prognostic information, and discussions of prognosis have been shown to enhance patient understanding of their illness. Such discussions can lead to high-quality, value-consistent care at the end of life, yet they are also often emotionally challenging. Despite how common and normal it is for patients to experience transient emotional distress when receiving ‘bad news’ about prognosis, emotional responses have been under-addressed in existing literature on prognostic discussions.

Areas covered: Drawing upon psychology research, principles of skilled clinical communication, and published approaches to discussions of serious illness, we summarize patients’ common emotional reactions and coping strategies. We then provide suggestions for how to respond to them in clinic.

Expert opinion: Ultimately, effective management of emotional reactions to bad news may lead to earlier, more frequent, and more transparent discussions of prognosis, thus promoting cancer patients’ understanding of, and adjustment to, their illness and improving the quality of their end-of-life care.     

Exploring the link between diabetes and pancreatic cancer

Introduction: Epidemiological studies indicate an association between type 2 diabetes and pancreatic cancer but the complex and multidirectional relationship between them remains unclear.

Areas covered: We summarized epidemiological evidence on diabetes and pancreatic cancer exploring the time–risk relationship. We described mechanisms linking long-standing diabetes to pancreatic cancer. We discussed pancreatic cancer-associated diabetes and its implication in the early detection of pancreatic cancer.

Expert opinion: The markedly increased risk of pancreatic cancer in patients with new-onset diabetes compared with long-standing diabetes observed in several epidemiological studies indicates a complex and bidirectional connection, with long-standing diabetes being a predisposing factor for pancreatic cancer (increasing the risk of the malignancy 1.5- to 2-fold) and new-onset diabetes an early manifestation of the tumor. Identifying clinical features and biomarkers to distinguish pancreatic cancer-associated diabetes from type 2 diabetes is an important goal to improve management and survival of this cancer. Imaging (MRI) for middle-age patients with new-onset diabetes may be considered.     

Sacituzumab govitecan: breakthrough targeted therapy for triple-negative breast cancer

Introduction: Triple negative breast cancer (TNBC) is an aggressive breast cancer subtype associated with an increased risk of recurrence and cancer-related death. Unlike hormone receptor-positive or HER2-positive breast cancers, there are limited targeted therapies available to treat TNBC and cytotoxic chemotherapy remains the mainstay of treatment. Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate targeting Trop-2 expressing cells and selectively delivering SN-38, an active metabolite of irinotecan.

Areas covered: This review covers the mechanism of action, safety and efficacy of sacituzumab govitecan in patients with previously treated, metastatic TNBC. Additionally, efficacy data in other epithelial malignancies is included based on a PubMed search for ‘sacituzumab govitecan’ and ‘clinical trial’.

Expert opinion: Sacituzumab govitecan has promising anti-cancer activity in patients with metastatic TNBC previously treated with at least two prior lines of systemic therapy based on a single arm Phase I/II clinical trial. A confirmatory Phase III randomized clinical trial is ongoing. Sacituzumab govitecan has a manageable side effect profile, with the most common adverse events being nausea, neutropenia, and diarrhea. The activity of sacituzumab govitecan likely extends beyond TNBC with promising early efficacy data in many other epithelial cancers, including hormone receptor-positive breast cancer.     

Capmatinib for the treatment of non-small cell lung cancer

Introduction: Activation of the MET pathway through MET amplifications or mutations is present in 3–4% of stage IV non-squamous non-small cell lung cancers (NSCLC). High MET amplifications and exon 14 skipping mutations are associated with poor prognosis: new treatments are needed for these patients. Capmatinib is a highly selective, potent small-molecule MET inhibitor with antitumor activity in NSCLC in vitro and in vivo.

Areas covered: This article provides an overview of the capmatinib clinical development program in NSCLC, both as monotherapy in NSCLC with a dysregulated MET pathway, and in combination with epidermal growth factor receptor (EGFR) inhibitor therapy in EGFR-mutant NSCLC with MET-based acquired resistance to previous EGFR inhibition.

Expert opinion: In the GEOMETRY Mono-1 study, treatment with capmatinib resulted in high response rates in stage IV NSCLC with MET exon 14 skipping mutations, particularly in first line, supporting testing for this biomarker at the time of diagnosis. Durable responses have been reported and results in MET-amplified NSCLC are eagerly anticipated. In EGFR-mutant NSCLC, notable responses have been observed in combination with an EGFR-tyrosine kinase inhibitor (TKI) in case of acquired resistance to EGFR-TKIs based on high MET amplification.     

The use of alternative therapies in conjunction with opioids for cancer pain

Introduction: There is a growing recognition of the role of interventional techniques (IT) for the management of cancer pain (CP). However, there are many controversies on how and when to use such techniques.

Areas covered: Patients who are unresponsive to systemic opioid analgesics or patients unable to tolerate systemic opioids may benefit from different IT for which the successful use depends on the selection of the right therapy for the right patient. The evidence regarding these techniques is often anecdotal and the potential risks, benefits, alternatives, and complications should be balanced to take a decision.

Expert opinion: The successful use of IT depends on many factors, including a careful assessment of previous treatments, patient’s characteristics, and the logistics. Risks, benefits, alternatives, and complications should be balanced to take a decision. Although IT have been described as effective in patients with CP, the evidence is still limited, unless for celiac plexus block, which has a high benefit-risk ratio. The intrathecal therapy should be chosen in patients who were poorly responding to opioid therapy, after an appropriate trial with different opioids. A careful selection of patients and techniques, a large experience in performing the procedures, sufficient logistics and staff skills, appropriate indications, and assessment of benefits and risks may help to achieve the best benefit for patients in individual cases.     

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.     

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.     

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.     

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-based therapy in myeloid malignancies: a promise yet to be fulfilled

Introduction: Immune system evasion is essential for tumor cell survival and is mediated by the immunosuppressive tumor microenvironment and the activation of inhibitory immune checkpoints. While immune checkpoint-based therapy yielded impressive results in several advanced solid malignancies such as melanoma and non-small cell lung cancer, its role in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) is still evolving.

Areas covered: Here we review the immunology in the tumor microenvironment in the bone marrow and discuss the current preclinical and clinical data for immune checkpoint-based therapy in myeloid neoplasms.

Expert commentary: Clinical trials of immune checkpoint inhibitors (ICI) in AML and MDS are still in early stages and reported results so far have been modest especially for monotherapy use in the refractory settings. However, there are preliminary data for synergistic effects for combination of multiple ICI with hypomethylating agents and conventional chemotherapy. ICI might also be effective in eradicating minimal residual disease and to prevent relapse following induction chemotherapy or hematopoietic stem cell transplant. Additional trials to provide insight into the efficacy and safety profile of immune checkpoint-based therapy, its optimal timing and potential combination with other types of therapy as well as identification of predictive biomarkers are needed.     

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.     

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.     

Advancing treatment of acute myeloid leukemia: the future of FLT3 inhibitors

Introduction: Mutations of the FLT3 gene are among most common genetic abnormalities occurring in acute myeloid leukemia (AML) and are associated with dismal prognosis. Tremendous effort has been devoted to developing clinically effective FLT3 inhibitors. First generation inhibitors consisted of multi-kinase inhibitors (sorafenib, lestaurtinib, midostaurin), which blocked FLT3 as well as multiple other kinase receptors. The failure of these agents to induce durable responses led to the development of second generation FLT3 tyrosine kinase inhibitors (quizartinib, crenolinib, gilteritinib) exhibiting high potency and specificity for mutant FLT3 kinases and sustained in vivo FLT3 inhibition. These myriad FLT3 inhibitors possess diverse kinase inhibitory properties, toxicity profiles, and pharmacokinetics, which impact on their incorporation into therapeutic regimens.

Areas covered: This article reviews the medical literature on current and future FLT3 inhibitors for AML therapy. We provide algorithms for which kinase inhibitor should be utilized for different FLT3 mutations (ITD±TKD) and clinical scenarios (de novo, relapsed/refractory, fit vs. unfit) and discuss novel FLT3 targeted therapeutic approaches.

Expert commentary: Integration of clinically active FLT3 inhibitors into all stages of therapy for all individuals with FLT3 mutant AML promises to significantly improve outcomes for this poor prognosis disease.     

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.     

Activated hepatic stellate cells promote progression of post-heat residual hepatocellular carcinoma from autophagic survival to proliferation

Background: Microscopic residual tumor often occurs after thermal ablation for medium-large hepatocellular carcinoma (HCC), leading to early aggressive recurrence or late relapse during follow-up. The mechanism how microscopic residual HCC cells survive sublethal heat stress and develop rapid outgrowth remains poorly understood.

Methods: HCC cells were exposed to sublethal heat treatment and co-cultured with conditioned media from activated HSCs (HSC-CM). Changes of cell proliferation, parameters of cell autophagy and activation of signaling pathways in heat-treated residual HCC cells were analyzed. An HCC orthotopic model was subjected to partial thermal ablation and antitumor effects of a combined treatment regimen were studied.

Results: HCC cells survived sublethal heat stress via activation of autophagy. HSC-CM enhanced autophagic survival within 24?h and then promoted proliferation of heat-treated residual HCC cells through HGF/c-Met signaling. Inhibition of autophagy or c-Met increased apoptosis of heat-treated residual HCC cells and reversed the protective effect of HSC-CM. HGF modulated biological status in autophagic survival or proliferation of heat-treated residual HCC through HGF/c-Met/ERK signaling and downstream components of ATG5/Beclin1 or cyclinD1. In an animal model, inhibiting autophagy in combination with c-Met inhibitor significantly thwarted tumor progression of residual HCC after incomplete thermal ablation via the suppressed autophagy, the decreased proliferation and the increased apoptosis.

Conclusions: Activated HSCs promote progression of residual HCC cells after sublethal heat treatment from autophagic survival to proliferation via HGF/c-Met signaling. A combined treatment regimen of inhibiting autophagy and c-Met signaling could be used to suppress tumor progression of residual HCC after incomplete thermal ablation.     

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.