[Show abstract][Hide abstract] ABSTRACT: The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m(2) day 1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Exploratory studies assessed DNA-based biomarkers [homologous recombination deficiency (HRD) score, and HR deficiency status (HRD score + BRCA1/BRCA2 mutation status)], protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3), and clinical pretreatment factors as predictors of pCR. 13/30 (43.3 %) patients enrolled in the study achieved pCR. 24 (80.0 %) had a clinical complete or partial response. The combination was safe with mostly grade 1 and 2 toxicities. HRD score (P = 0.0024) and HR deficiency status (P = 0.0012) significantly predicted pCR. Pretreatment cytoplasmic CDK2 was also associated with pCR (P = 0.021). Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D (P = 0.020), nuclear CDK4 (P = 0.0030), and nuclear Smad3 (P = 0.015) were detected. The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC. HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pCR in this patient population.
Breast Cancer Research and Treatment 05/2015; 151(3). DOI:10.1007/s10549-015-3435-y · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Palliative care is a fundamental component of cancer care. As part of the 2011 to 2012 Leadership Development Program (LDP) of the American Society of Clinical Oncology (ASCO), a group of participants was charged with advising ASCO on how to develop a service model integrating palliative care throughout the continuum of cancer care. This article presents the findings of the LDP group. The group focused on the process of palliative care delivery in the oncology setting. We identified key elements for models of palliative care in various settings to be potentially equitable, sustainable, feasible, and acceptable, and here we describe a dynamic model for the integrated, simultaneous implementation of palliative care into oncology practice. We also discuss critical considerations to better integrate palliative care into oncology, including raising consciousness and educating both providers and the public about the importance of palliative care; coordinating palliative care efforts through strengthening affiliations and/or developing new partnerships; prospectively evaluating the impact of palliative care on patient and provider satisfaction, quality improvement, and cost savings; and ensuring sustainability through adequate reimbursement and incentives, including linkage of performance data to quality indicators, and coordination with training efforts and maintenance of certification requirements for providers. In light of these findings, we believe the confluence of increasing importance of incorporation of palliative care education in oncology education, emphasis on value-based care, growing use of technology, and potential cost savings makes developing and incorporating palliative care into current service models a meaningful goal.
[Show abstract][Hide abstract] ABSTRACT: Achieving balance in the appropriate use of opioids for the treatment of cancer pain is complex. The definition of "balance" is continually being modified. Palliative care professionals, pain specialists, and oncologists have long been advocating for the aggressive management of pain for patients with advanced cancer. Some progress has been made in this arena but barriers persist. Fear of addiction by patients, family members, and oncology professionals presents a serious obstacle to the provision of adequate pain control. This is further complicated by societal factors that receive extensive media coverage, such as diversion of prescribed opioids for recreational use and increasing deaths as a result of this inappropriate use of prescription opioids. This growing concern has led to more opioid regulation, which increases obstacles to pain management in this population. Another evolving concern is whether the long-term use of opioids is safe and effective. Data from the chronic nonmalignant pain literature suggest that toxicities may result and misuse has been underestimated, yet little information is available in the cancer population. These issues lead to serious questions regarding how balance might be successfully achieved for patients in an oncology setting. Can pain relief be provided while reducing negative consequences of treatment? Which patient should be prescribed what medications, in what situations, for what kind of pain, and who should be managing the pain?
[Show abstract][Hide abstract] ABSTRACT: Burnout among physicians can lead to decreased career satisfaction, physical and emotional exhaustion, and increased medical errors. In oncologists, high exposure to fatal illness is associated with burnout.
The Maslach Burnout Inventory, measuring Emotional Exhaustion (EE), Depersonalization (DP), and Personal Accomplishment (PA), was administered to second-year US oncology fellows. Bivariate and multivariate analyses explored associations between burnout and fellow demographics, attitudes, and educational experiences.
A total of 254 fellows out of 402 eligible US fellows responded (63.2%) and 24.2% reported high EE, 30.0% reported high DP, and 26.8% reported low PA. Over half of the fellows reported burnout in at least one domain. Lower EE scores were associated with the fellows' perceptions of having received better teaching, explicit teaching about certain end-of-life topics, and receipt of direct observation of goals-of-care discussions. Fellows who reported better overall teaching quality and more frequent observation of their skills had less depersonalization. Fellows who felt a responsibility to help patients at the end of life to prepare for death had higher PA.
This survey relies on the fellows' self-reported perceptions without an objective measure for validation. Factors associated with burnout may not be causal. The number of analyses performed raises the concern for Type I errors; therefore, a stringent P value (0.01) was used.
Burnout is prevalent during oncology training. Higher-quality teaching is associated with less burnout among fellows. Fellowship programs should recognize the prevalence of burnout among oncology fellows as well as components of training that may protect against burnout.
The journal of supportive oncology 06/2013; 11(2):95-102. DOI:10.12788/j.suponc.001
[Show abstract][Hide abstract] ABSTRACT: Background:
This study sought to develop a predictive model for 30-day mortality in hospitalized cancer patients, by using admission information available through the electronic medical record.
Observational cohort study of 3062 patients admitted to the oncology service from August 1, 2008, to July 31, 2009. Matched numbers of patients were in the derivation and validation cohorts (1531 patients). Data were obtained on day 1 of admission and included demographic information, vital signs, and laboratory data. Survival data were obtained from the Social Security Death Index.
The 30-day mortality rate of the derivation and validation samples were 9.5% and 9.7% respectively. Significant predictive variables in the multivariate analysis included age (P < .0001), assistance with activities of daily living (ADLs; P = .022), admission type (elective/emergency) (P = .059), oxygen use (P < .0001), and vital signs abnormalities including pulse oximetry (P = .0004), temperature (P = .017), and heart rate (P = .0002). A logistic regression model was developed to predict death within 30 days: Score = 18.2897 + 0.6013*(admit type) + 0.4518*(ADL) + 0.0325*(admit age) - 0.1458*(temperature) + 0.019*(heart rate) - 0.0983*(pulse oximetry) - 0.0123 (systolic blood pressure) + 0.8615*(O2 use). The largest sum of sensitivity (63%) and specificity (78%) was at -2.09 (area under the curve = -0.789). A total of 25.32% (100 of 395) of patients with a score above -2.09 died, whereas 4.31% (49 of 1136) of patients below -2.09 died. Sensitivity and positive predictive value in the derivation and validation samples compared favorably.
Clinical factors available via the electronic medical record within 24 hours of hospital admission can be used to identify cancer patients at risk for 30-day mortality. These patients would benefit from discussion of preferences for care at the end of life.
Cancer 06/2013; 119(11). DOI:10.1002/cncr.27974 · 4.89 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Palliative cancer care is the integration into oncologic care of therapies that address the issues that cause physical and psychosocial suffering for the patient and family. Effective provision of palliative cancer care requires an interdisciplinary team that can provide care in all settings (home, inpatient, and outpatient). There is clear evidence for improved outcomes in multiple domains-symptoms, quality of end-of-life care, provider satisfaction, cost of care-with the integration of palliative care into cancer care. As a result, there are now guideline-based recommendations for incorporating palliative care into cancer care. Unfortunately there continue to be barriers to effective integration; these include gaps in education and research, and a cultural stigma that equates palliative care with end-of-life care. These barriers will need to be addressed in order to achieve seamless palliative care integration across the continuum of cancer care for all patients and their families.
[Show abstract][Hide abstract] ABSTRACT: As management of patients with cancer is evolving, an increased focus is being placed on individualized patient-centered care. Early integration of palliative care into the overall management of patients with cancer can help achieve this paradigm shift. Despite recommendations for earlier integration of palliative care by national and international societies, several barriers remain to achieving this goal. Survey studies have indicated a significant need for increased education regarding palliative care for both medical undergraduates and postgraduate physicians. Key issues in the early integration of palliative care include relationship-building across multiple health systems and specialties; development of a standardized definition of palliative care, making clear that it should be fully integrated with cancer-directed therapy; identification of physician and nonphysician champions; standardization of tools for patient assessment; education programs designed to meet the needs of health care professionals; and ongoing evaluation to assess program benefits and limitations.
Journal of the National Comprehensive Cancer Network: JNCCN 03/2013; 11 Suppl 1:S11-6. · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: ABSTRACT Despite the recent advances in cancer therapeutics for Lymphoma (Lym), a continuum of disease, treatment, and psychological challenges remain for the clinical management of the Lym patient adversely impacting health-related quality of life. In response, this study presents the development and validation of the NCCN-FACT Lymphoma Symptom Index-18 (FLymSI-18). Advanced Lym patients (N=50) rated the significance of 40 symptoms and hematologists-oncologists (N=10) rated these symptoms according to importance and disease-related or treatment-related origin. Patient symptom priorities were unified with clinician-priorities for symptom measurement in Lym for instrument development. Reliability estimates indicate FLymSI-18 has acceptable internal consistency (α=0.87), content validity, and concurrent validity as indicated by moderate to strong correlations with the FACIT. Overall, the FLymSI-18 provides evidence for reliability and validity as a brief assessment of the most important symptoms associated with advanced Lym in the clinical trial research environment.
[Show abstract][Hide abstract] ABSTRACT: These guidelines were developed and updated by an interdisciplinary group of experts based on clinical experience and available scientific evidence. The goal of these guidelines is to help patients with cancer experience the best quality of life possible throughout the illness trajectory by providing guidance for the primary oncology team for symptom screening, assessment, palliative care interventions, reassessment, and afterdeath care. Palliative care should be initiated by the primary oncology team and augmented by collaboration with an interdisciplinary team of palliative care experts.
Journal of the National Comprehensive Cancer Network: JNCCN 10/2012; 10(10):1284-309. · 4.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: CONTEXT: The Functional Assessment of Cancer Therapy-Head and Neck is a well-validated assessment of quality of life used with patients diagnosed with head and neck cancers (HCNs). The present study is an attempt to evaluate and modify this instrument as necessary in light of the recent regulatory guidelines from the Food and Drug Administration on the use of patient-reported outcomes in clinical trials. OBJECTIVES: Overall, the goal was to identify patients' highest priority cancer symptoms, compare these symptoms with those suggested by oncology experts, and construct a brief symptom index to assess these symptoms and categorize them as treatment-related, disease-related, or related to general function and well-being. METHODS: Patients (N=49) with advanced (Stages III and IV) HCNs were recruited from participating National Comprehensive Cancer Network institutions and community cancer support organizations in the Chicago area. Patients completed open-ended interviews and symptom checklists. Participating oncology physician experts also rated symptoms. Content validity was obtained by evaluating results alongside items in the Functional Assessment of Chronic Illness Therapy system. Eleven oncologists categorized symptoms in terms of importance and also whether the symptoms were primarily related to disease, treatment, or functional well-being. RESULTS: HCN-related symptoms endorsed as high priority by both patients and oncology experts were selected for the new National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Head and Neck Cancer Symptom Index-22. The final version includes 22 items, which are broken down into disease-related symptoms, treatment side effects, or general function and well-being. The new scale has acceptable internal consistency (Cronbach's coefficient alpha=0.86), content validity for use in chemotherapy trials of patients with advanced disease, and concurrent validity as demonstrated by moderate-to-strong correlations with the existing Functional Assessment of Chronic Illness Therapy measure. CONCLUSION: The National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Head and Neck Cancer Symptom Index-22 adequately reflects symptom and side effect concerns of advanced HCN patients as well as oncology physicians. This instrument can be used to evaluate the most important disease-related symptoms, treatment side effects, and function/well-being in patients with advanced HCNs in clinical practice and research.
Journal of pain and symptom management 09/2012; 46(1). DOI:10.1016/j.jpainsymman.2012.06.004 · 2.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: By using methods consistent with recent regulatory guidance on patient-reported outcomes as endpoints in clinical trials, we created a new version of the Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index (FBSI), with emphasis on patient input during the development process.
We obtained input on the most important symptoms to monitor during treatment for stage III or IV breast cancer from 52 patients recruited from National Comprehensive Cancer Network institutions as well as support service organizations. Participating patients shared their top-priority symptoms/concerns through open-ended interviews and symptom checklists. To ensure adequate content coverage, we evaluated results alongside the original version of the FBSI, which was created on the basis of a survey of oncology clinicians at National Comprehensive Cancer Network institutions and items in the Functional Assessment of Chronic Illness Therapy measurement system. We also obtained input from 10 National Comprehensive Cancer Network oncologists regarding whether symptoms were primarily related to disease or treatment.
We selected breast cancer-related symptoms and concerns endorsed as high priority by both oncology patients and clinicians for inclusion in the new National Comprehensive Cancer Network-Functional Assessment of Cancer Therapy-Breast Cancer Symptom Index-16 (NFBSI-16), which includes all eight items from the original FBSI and eight additional items from Functional Assessment of Chronic Illness Therapy measures. The NFBSI-16 is formatted by subscale: Disease-Related Symptom, Treatment Side-Effect, and General Function and Well-Being. Results provide preliminary support for NFBSI-16's internal consistency reliability (α = 0.87) and validity as evidenced by moderate-to-strong relationships with expected criteria.
Reflecting the priority symptoms of breast cancer patients and clinicians, the NFBSI-16 can be used to help evaluate the effectiveness of treatments for advanced breast cancer in clinical practice and research.
Value in Health 02/2012; 15(1):183-90. DOI:10.1016/j.jval.2011.08.1739 · 3.28 Impact Factor