Patrick Chaftari

Association of Body Composition with Outcome of Docetaxel Chemotherapy in Metastatic Prostate Cancer: A Retrospective Review

Background Docetaxel, a lipophilic drug, is indicated for castration-resistant metastatic prostate cancer. Most men with such disease would have had androgen-deprivation therapy, which decreases muscle and increases body fat. Obesity and body composition changes may influence the outcomes of docetaxel therapy. Methods We conducted a retrospective review of 333 patients with metastatic prostate cancer treated with docetaxel at a comprehensive cancer center between October 7, 2004 and December 31, 2012. Body composition parameters were measured based on the areas of muscle and adipose tissues in the visceral and subcutaneous compartments on CT images at L3-4 levels. Dose calculations, toxicity and adverse reaction profiles, and overall survival were analyzed. Results Obese patients were younger at the diagnosis of prostate cancer and had a shorter duration from diagnosis to docetaxel therapy. Analysis of body composition found that a high visceral fat-to-subcutaneous fat area ratio (VSR) was associated with poor prognosis but a high visceral fat-to-muscle area ratio (VMR) and high body mass index were associated with increased duration from starting docetaxel to death, allowing such men to catch up with patients with normal body mass index in overall survival from cancer diagnosis to death. Cox proportional hazard regression showed that age ≥65 years, high VSR, abnormal serum alkaline phosphatase, and >10% reduction of initial dosage were significant predictors of shorter time between starting docetaxel and death, and that high VMR, obesity, and weekly regimens were significant predictors of longer survival after docetaxel. Conclusion Obese and overweight patients may benefit more from weekly docetaxel regimens using the reference dosage of 35 mg/m2 without empirical dosage reduction.

Procalcitonin Guiding Antimicrobial Therapy Duration in Febrile Cancer Patients with Documented Infection or Neutropenia

In this analysis, we identified febrile cancer patients with documented infections or neutropenia, whose procalcitonin levels are low at baseline or decrease on antibiotics. These patients had similar outcomes in terms of mortality and relapse of infection regardless of the duration of antimicrobial therapy (less or more than 7 days).

Biomarkers of Sepsis and Bloodstream Infections: The Role of Procalcitonin and Proadrenomedullin With Emphasis in Patients With Cancer

Sepsis and bloodstream infections remain a leading cause of death in immunocompromised patients with cancer. The management of these serious infections consist of empiric use of antimicrobial agents which are often overused. Procalcitonin and proadrenomedullin are biomarkers that have been extensively evaluated in the general populations but with little emphasis in the population immunocompromised patients with cancer, where they may have promising roles in the management of febrile patients. In this review, we summarize the available evidence of the potential role of these available biomarkers in guiding antimicrobial therapy to optimize the use of resources in the general patient population. Special emphasis is given to the role of these 2 biomarkers in the immunocompromised and critically ill patients with cancer, highlighting the distinctive utility of each.

Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center

Study objective Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune‐related adverse effects among cancer patients visiting emergency departments (EDs). Methods We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune‐related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune‐related adverse effect with overall survival from the ED visit to death. Results We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune‐related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival. Conclusion Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune‐related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.

Presenting Symptoms in the Emergency Department as Predictors of Intensive Care Unit Admissions and Hospital Mortality in a Comprehensive Cancer Center.

PURPOSE The identification of patients at high risk for poor outcomes may allow for earlier palliative care and prevent futile interventions. We examined the association of presenting symptoms on risk of intensive care unit (ICU) admission and hospital death among patients with cancer admitted through an emergency department (ED). METHODS We queried MD Anderson Cancer Center databases for all patients who visited the ED in 2010. Presenting symptoms, ICU admissions, and hospital deaths were reviewed; patient data analyzed; and risk factors for ICU admission and hospital mortality identified. RESULTS The main presenting symptoms were pain, fever, and respiratory distress. Of the patients with cancer who visited the ED, 5,362 (58%) were admitted to the hospital at least once (range, 1 to 13 admissions), 697 (13%) were admitted to the ICU at least once, and 587 (11%) died during hospitalization (31% of 233 patients with hematologic malignancies and 27% of 354 patients with solid tumors died in the ICU; P < .001). In multivariable logistic regression, presenting symptoms of respiratory distress or altered mental status; lung cancer, leukemia, or lymphoma; and nonwhite race were independent predictors of hospital death. Patients who died had a longer median length of hospital stay than patients discharged alive (14 v 6 days for hematologic malignancies and 7 v 5 days for solid tumors; P < .001). CONCLUSION Patients with cancer admitted through an ED experience high ICU admission and hospital mortality rates. Patients with advanced cancer and respiratory distress or altered mental status may benefit from palliative care that avoids unnecessary interventions.

Advance care planning: challenges at the emergency department of a cancer care center

IntroductionCode status discussions form an important part of advance care planning (ACP) as it enables physicians to respect the patient’s wishes for end-of-life care. However, in some cases, code status discussions can be challenging causing the physician to go against the patient’s wishes and the code of medical ethics. This is especially true in an emergency setting. In this paper, we will discuss three cases of advanced cancer patients, where code status discussions posed challenges to healthcare providers.Case reportsIn the first case, the patient was a 26-year-old male diagnosed with advanced osteosarcoma. Code status was discussed with him, while he was still functional, wherein he agreed to a do-not-resuscitate (DNR) order. However, at the time of end-of-life care, despite of previous code status agreement, the patient’s mother insisted on full code. As a result, the DNR order was reverted and the patient was intubated. The second case discusses an 83-year-old female patient with metastatic gastric cancer. Code status was extensively discussed with the patient and her son who agreed to sign a DNR order. This case posed a challenge because when the patient’s condition deteriorated, her son demanded cardioversion and other aggressive treatment measures without any chest compressions or intubation. In the third case, the patient was a 40-year-old woman with advanced metastatic adenocarcinoma with neuroendocrine features of the parotid. On admission to the ED, as per the patient’s wishes expressed by her husband, a DNR/DNI order was placed. However, this order had to be reverted when the patient’s aunt and sister opposed vehemently to the DNR/DNI order.ConclusionThe three cases demonstrate the challenges that can arise in the implementation of code status order in the ED as it pertains for end-of-life care. In any scenario, respecting the patient’s wishes and adherence to the code of medical ethics take precedence over any familial objections arising difficulties with coping.

Genome-wide association study identifies genes associated with neuropathy in patients with head and neck cancer

Neuropathic pain (NP), defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system, is a debilitating chronic pain condition often resulting from cancer treatment. Among cancer patients, neuropathy during cancer treatment is a predisposing event for NP. To identify genetic variants influencing the development of NP, we conducted a genome-wide association study in 1,043 patients with squamous cell carcinoma of the head and neck, based on 714,494 tagging single-nucleotide polymorphisms (SNPs) (130 cases, 913 controls). About 12.5% of the patients, who previously had cancer treatment, had neuropathy-associated diagnoses, as defined using the ICD-9/ICD-10 codes. We identified four common SNPs representing four genomic regions: 7q22.3 (rs10950641; SNX8; P = 3.39 × 10−14), 19p13.2 (rs4804217; PCP2; P = 2.95 × 10−9), 3q27.3 (rs6796803; KNG1; P = 6.42 × 10−9) and 15q22.2 (rs4775319; RORA; P = 1.02 × 10−8), suggesting SNX8, PCP2, KNG1 and RORA might be novel target genes for NP in patients with head and neck cancer. Future experimental validation to explore physiological effects of the identified SNPs will provide a better understanding of the biological mechanisms underlying NP and may provide insights into novel therapeutic targets for treatment and management of NP.

Improvement of Smoking Abstinence Rates with Increased Varenicline Dosage

Purpose/Background It is unclear whether increasing the dose of varenicline beyond the standard dose of 2 mg/d would improve smoking abstinence. Methods We examined the effect of 3 mg/d of varenicline on smoking abstinence among smokers who had reduced their smoking by 50% or more in response to 2 mg/d for at least 6 weeks but had not quit smoking. Of 2833 patients treated with varenicline, dosage of a subset of 73 smokers was increased to 3 mg/d after 6 weeks. We used a propensity score analysis involving multiple baseline covariates to create a comparative sample of 356 smokers who remained on 2 mg/d. All smokers received concurrent and similar smoking-cessation counseling. Results At 3 months, we found higher 7-day point prevalence smoking-abstinence rate in the 3-mg group (26%) than in the 2-mg group (11.5%, &khgr;2 = 10.60, P < 0.001; risk ratio [RR], 2.3; 95% confidence interval [CI], 1.4–3.6). The difference in abstinence rates remained significant at the 6-month (P < 0.001; RR, 2.6; 95% CI, 1.6–3.9) and 9-month follow-up (P < 0.001; RR, 2.2; 95% CI, 1.4–3.3). Conclusions A relatively small increase in the daily dose of varenicline seems to offer a benefit for those who are not able to achieve total abstinence after approximately 6 weeks of 2 mg/d.

Emergency Department Intervention Program for Enhancing Choice at the Endof Life: A Quality Improvement Project at a Comprehensive Cancer Center

Background: Advance care planning (ACP) for end-of-life care is especially important for individuals with terminal illnesses such as advanced cancer. It ensures that patients’ wishes are honored and alleviates the decisionmaking burden on family members and medical providers. It reduces unnecessary medical costs, and prevents waste of valuable resources. We proposed a quality improvement project to improve documentation of advanced care directives in the Emergency Department (ED) of a tertiary cancer center. Methods: We developed a pocket card to help emergency physicians screen patients in need of ACP. The goal was to assist ED staff in initiating conversations about end-of-life issues, and encourage patients and their caregivers to get involved in decisions about their medical treatment. Intervention: The project was implemented in a Plan-Do-Study-Act design. Baseline data was collected from the medical records of all patients visiting the ED on seven consecutive days prior to the distribution of the pocket card tool. After the launch of the intervention, the charts of all patients visiting the emergency center were reviewed for documentation of advanced care planning. Metrics polled included presence of a health care power of attorney and determination of code status, specifically the do-not-resuscitate (DNR) status. Results: 429 patients who visited the ED seven consecutive days prior to institution of the screening tool. Of these, we found that 66 (15.4%) had indicated their do-not-resuscitate (DNR) status in their charts, and 82 (19.1%) had a health care power of attorney. Post launch of the intervention, 391 patients visited the ED over seven consecutive days. Of these, 125 (32.0%) indicated their DNR status in their charts before leaving the ED, and 95 (24.3%) had a health care power of attorney. After implementation of our screening tool, there was a 107.8% increase in documentation of DNR status and a 76% increase in patients with a health care power of attorney. Conclusions: In this quality improvement project, a straightforward, low cost intervention was successfully implemented to improve documentation of patients’ ACP goals.

Methotrexate-induced leukoencephalopathy presenting as stroke in the emergency department

Methotrexate‐induced leukoencephalopathy is to be considered as a potential etiology in any patient presenting with stroke‐like symptoms after receiving methotrexate. One of our cases suggests that the method of administration of the methotrexate can be IV or intrathecal and still results in leukoencephalopathy.