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.     

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.     

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.     

Hedgehog pathway inhibition as a therapeutic target in acute myeloid leukemia

Introduction: The Hedgehog (HH) pathway constitutes a collection of signaling molecules which critically influence embryogenesis. In adults, however, the HH pathway remains integral to the proliferation, maintenance, and apoptosis of adult stem cells including hematopoietic stem cells.

Areas covered: We discuss the current understanding of the HH pathway as it relates to normal hematopoiesis, the pathology of acute myeloid leukemia (AML), the rationale for and data from combination therapies including HH pathway inhibitors, and ultimately the prospects that might offer promise in targeting this pathway in AML.

Expert opinion: Efforts to target the HH pathway have been focused on impeding this disposition and restoring chemosensitivity to conventional myeloid neoplasm therapies. The year 2018 saw the first approval of a HH pathway inhibitor (glasdegib) for AML, though for an older population and in combination with an uncommonly-used therapy. Several other clinical trials with agents targeting modulators of HH signaling in AML and MDS are underway. Further study and understanding of the interplay between the numerous aspects of HH signaling and how it relates to the augmented survival of AML will provide a more reliable substrate for therapeutic strategies in patients with this poor-risk disease.     

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.     

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.     

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.     

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.     

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.     

Adjuvant therapeutic approaches of HER2-positive breast cancer with a focus on neratinib maleate

Introduction: Breast cancer (BC) is the most common cancer in women. Human epidermal growth factor receptor 2-positive (HER2-positive) BC represents up to 15% of all BC cases and is associated with a poor prognosis. Despite the substantial improvement obtained with the addition to the treatment of trastuzumab in this subtype of BC, disease recurrence can still occur.

Areas covered: Anti-HER2 targeting drugs such as trastuzumab, pertuzumab, and T-DM1 have shown significant results in (neo)adjuvant setting. In this article, we will focus on available data for neratinib to reduce BC recurrence based mainly on the results of the ExteNET trial. This trial aimed to investigate whether neratinib can further reduce the risk of recurrence of patients diagnosed with HER2-positive BC. This trial demonstrated a significant reduction in the risk of invasive disease-free survival, particularly in hormone receptor-positive population. In addition, this review provides an expert opinion and analysis of the current situation in the adjuvant HER2-positive BC setting and in particular the escalation strategy of HER2 targeting.

Expert opinion: The treatment landscape of HER2 positive BC in this setting will evolve in the coming years with a need for clinical and molecular perspective tools to guide therapy.     

New and important changes in breast cancer TNM: incorporation of biologic factors into staging

Introduction: Cancer staging has historically been based solely on the anatomic extent of the tumor (T), spread to lymph nodes (N), and the presence of distant metastases (M). More recently biologic factors have been added to modify TNM stage groups to provide more accurate prognosis for patients.

Areas covered: The American Joint Committee on Cancer (AJCC) updated breast cancer staging in 2016 to include T, N, M, tumor grade and expression of estrogen and progesterone receptors and HER2. Addition of these factors changed the stage group for a large fraction of cases compared to prior TNM stage groupings. This updated ‘prognostic stage’ provides more robust and precise prognosis information.

Expert opinion: Inclusion of biological information in staging changes the meaning and the use of stage in clinical practice. This paper reviews the evidence supporting these changes, limitations affecting staging, and discusses the implications for clinical practice and the future of breast cancer staging.     

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.     

The evolving role of receptors as predictive biomarkers for metastatic breast cancer

Introduction: In breast cancer, estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2) are essential biomarkers to predict response to endocrine and anti-HER2 therapies, respectively. In metastatic breast cancer, the use of these receptors and targeted therapies present additional challenges: temporal heterogeneity, together with limited sampling methodologies, hinders receptor status assessment, and the constant evolution of the disease invariably leads to resistance to treatment.

Areas covered: This review summarizes the genomic abnormalities in ER and HER2, such as mutations, amplifications, translocations, and alternative splicing, emerging as novel biomarkers that provide an insight into underlying mechanisms of resistance and hold potential predictive value to inform treatment selection. We also describe how liquid biopsies for sampling of circulating markers and ultrasensitive detection technologies have emerged which complement ongoing efforts for biomarker discovery and analysis.

Expert commentary: While evidence suggests that genomic aberrations in ER and HER2 could contribute to meeting the pressing need for better predictive biomarkers, efforts need to be made to standardize assessment methods and better understand the resistance mechanisms these markers denote. Taking advantage of emerging technologies, research in upcoming years should include prospective trials incorporating these predictors into the study design to validate their potential clinical value.     

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.     

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.     

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.     

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.     

Successful treatment of a BRAF V600E-mutant extracranial metastatic anaplastic oligoastrocytoma with vemurafenib and everolimus

Background: Extracranial metastasis is a rare phenomenon of anaplastic oligoastrocytoma. When patients progress after comprehensive treatment, there is often no effective treatment. Rapid development of gene detection technology makes precision treatment of glioma possible.

Patient and methods: A 22-year-old girl was firstly diagnosed with anaplastic oligoastrocytoma WHO grade III-IV in 2014, and progressed rapidly after chemoradiotherapy in multiple extraneural lesions in 2016. She was expected to have a short life and Next-Generation Sequencing (NGS) was applied.

Results: Mutation of BRAF (V600E) was reported by 1st NGS and oral vemurafenib stabilized her disease for 6 months. PIK3CA was reported by 2nd NGS after her progression of vemurafenib. The oral administration of everolimus together with vemurafenib stabilized her disease for another 6 months. However, the patient died due to the rapid progression of the disease on 24 February 2018.

Conclusion: We successfully treated a BRAF V600E-mutated anaplastic oligoastrocytoma with multiple extraneural metastases with vemurafenib and everolimus. For late-staged patients who have no clear and effective treatment plan, NGS may serve as an effective option.