Oncologic emergencies: Pathophysiology, presentation, diagnosis, and treatment.

Oncologic emergencies can occur at any time during the course of a malignancy, from the presenting symptom to end-stage disease. Although some of these conditions are related to cancer therapy, they are by no means confined to the period of initial diagnosis and active treatment. In the setting of recurrent malignancy, these events can occur years after the surveillance of a cancer patient has been appropriately transferred from a medical oncologist to a primary care provider. As such, awareness of a patient's cancer history and its possible complications forms an important part of any clinician's knowledge base. Prompt identification of and intervention in these emergencies can prolong survival and improve quality of life, even in the setting of terminal illness. This article reviews hypercalcemia, hyponatremia, hypoglycemia, tumor lysis syndrome, cardiac tamponade, superior vena cava syndrome, neutropenic fever, spinal cord compression, increased intracranial pressure, seizures, hyperviscosity syndrome, leukostasis, and airway obstruction in patients with malignancies. Chemotherapeutic emergencies are also addressed.

Low level of hepatitis B virus screening among patients receiving chemotherapy.

BACKGROUND & AIMS: Chemotherapy of patients with inactive hepatitis B virus (HBV) infection can lead to viral reactivation and hepatitis flares. We investigated the proportion of patients screened for HBV infection before chemotherapy over time and the outcomes of screened patients. METHODS: In a retrospective study, we collected data from a pharmacy database on patients who underwent cytotoxic chemotherapy for solid or hematologic malignancies at the Mayo Clinic in Rochester, Minnesota, from January 1, 2006, through September 30, 2011. Laboratory data were collected from electronic medical records. Screening was identified based on tests for hepatitis B surface antigen, for any reason at any time before chemotherapy. RESULTS: Of 8005 patients undergoing chemotherapy, 1279 (16%) were screened for HBV infection before chemotherapy, including 668 of 1805 patients with hematologic malignancies (37%). The proportion of patients screened for HBV increased from 14.3% in 2006 to 2008 to 17.7% in 2009 to 2011 (P < .01). This trend was attributed mostly to an increase in the proportion of patients with hematologic malignancies, from 32.7% in 2006 to 2008 to 40.6% in 2009 to 2011 (P < .01). Of 13 patients who tested positive for HBV, 5 did not receive prophylactic antiviral therapy; HBV infection was reactivated in 2 of these patients. None of the 8 patients who received an antiviral agent before chemotherapy experienced HBV reactivation. Of 58 unscreened patients who had increases in their alanine aminotransferase level (>300 U/L), only 1 patient appeared to have an undiagnosed HBV infection. CONCLUSIONS: Only a small percentage of patients receiving chemotherapy are screened for HBV infection. However, a larger proportion of patients was screened during 2009 to 2011 than during 2006 to 2008, especially patients with hematologic malignancies. Strategies are needed to ensure that patients receiving chemotherapy are protected from the consequences of undiagnosed HBV infection.

Cryoablation of sternal metastases for pain palliation and local tumor control.

PURPOSE: To determine safety and effectiveness of cryoablation of sternal metastases for pain palliation and local tumor control. MATERIALS AND METHODS: A tumor ablation database was retrospectively reviewed for sternal cryoablation procedures performed between January 2005 and June 2013, which yielded 15 procedures to treat 12 sternal metastases in 12 patients (five men). Median patient age was 57 years (range, 38-80 y). Metastases arose from five primary sites (breast, lung, kidney, ampulla, and thyroid), and median tumor size was 3.8 cm (range, 2.2-7.5 cm). Seven patients (58%) underwent cryoablation for pain palliation, and five (42%) underwent cryoablation for local tumor control of oligometastatic disease. Clinical outcomes (including complications, local tumor control, and pain response) were evaluated retrospectively. RESULTS: Mean pain scores decreased from 7.0 ± 1.9 (median, 7; range, 4-10) at baseline to 1.8 ± 1.2 (median, 1.5; range, 0-4) following cryoablation (P = .00049). Two patients had durable pain palliation, and four had greater than 1 month of pain relief, with a median duration of 5.7 months (range, 1.5-14.7 mo). Two patients in whom recurrent pain developed underwent repeat cryoablation, with durable pain relief. Allowing for a single repeat treatment, local tumor control was achieved in four of five patients (80%) treated for this indication, with median follow-up of 8.4 months (range, 2.6-13.6 mo). In one patient (8%), an infectious complication developed that was successfully treated with antibiotics on an outpatient basis. CONCLUSIONS: Cryoablation is a safe and potentially effective treatment for patients with painful sternal metastases and can achieve local tumor control in select patients.

An exploratory pilot study of palliative medicine compared to anesthesia-pain consultation for pain in patients with cancer.

Oncologists often manage cancer-associated symptoms including pain. When symptoms are severe, anesthesia-pain medicine (APM) and/or palliative medicine (PM) can effectively treat symptoms. Nevertheless, symptom management may be suboptimal, leading to diminished quality of life (QOL). We assessed the value of PM vs. APM consultation in cancer patients referred for pain management alone. Patients referred to an APM-based Cancer Pain Clinic (CPC) over an 8-month period were evaluated by PM or APM based on the first available appointment. Symptoms and QOL were assessed by the MD Anderson Symptom Inventory and Linear Analog Self-Assessment at baseline and 4-6 weeks after initial encounter. Data were analyzed on an available-case basis. Sixty-two patients (37 PM, 25 APM) completed the initial survey, with 48 patients (31 PM, 17 APM) completing followup. Mean pain score improved from 7.97 to 5.47 in the PM group (P < 0.0001) and from 7.1 to 4.5 (P = 0.29) in the APM group. The PM group demonstrated a clinically significant improvement in 8/19 symptoms vs. 3/19 in the APM group and in 3/5 QOL parameters in the PM group vs. 1/5 in the APM group. Our small sample size weakens our power and ability to detect significant differences between the groups. Only one follow-up symptom-assessment point was obtained. PM consultation is as effective as APM in improving cancer pain but may be more effective with symptom management and improving QOL.

Resurrecting the Hospital Autopsy: Impact of an Office of Decedent Affairs on Consent Rates, Providers, and Next-of-Kin.

CONTEXT.­: Autopsy rates have decreased dramatically despite providing important clinical information to medical practices and social benefits to decedents' families. OBJECTIVE.­: To assess the impact of an institutional Office of Decedent Affairs (ODA), a direct communication link between pathology and decedents' families, on hospital autopsy consent rates, autopsy-related communication, practitioner views, and next-of-kin experiences. DESIGN.­: A before and after study involving all hospital decedents whose deaths did not fall within the jurisdiction of the medical examiner's office from 2013 to 2018. A pathology-run ODA launched in May 2016 to guide next-of-kin through the hospital death process (including autopsy-related decisions) and serve as the next-of-kin's contact for any subsequent autopsy-related communication. Critical care and hematology/oncology practitioners were assessed for their autopsy-related views and decedents' next-of-kin were assessed for their autopsy-related experiences. Autopsy consent rates for non-medical examiner hospital deaths, autopsy-related communication rates, practitioner views on the role and value of autopsy, and next-of-kin autopsy experiences and decisions factors were compared prior to and after ODA launch. RESULTS.­: Autopsy consent rates significantly increased from 13.2% to 17.3% (480 of 3647 deaths versus 544 of 3148 deaths; P < .001). There were significant increases in the rate of autopsy-related discussions and bereavement counseling provided to decedents' families. Practitioner views on the positive role of autopsy for any hospital death and those with advanced stage cancer also significantly increased. Next-of-kin indicated more consistent autopsy-related discussions with the potential benefits of autopsy discussed becoming key decision factors. CONCLUSIONS.­: An ODA improves hospital autopsy consent rates, autopsy-related communication, providers' autopsy-related views, and next-of-kins autopsy experiences.

Pre- and Postoperative Neratinib for HER2-Positive Breast Cancer Brain Metastases: Translational Breast Cancer Research Consortium 022.

PURPOSE: This pilot study was performed to test our ability to administer neratinib monotherapy before clinically recommended craniotomy in patients with HER2-positive metastatic breast cancer to the central nervous system, to examine neratinib's central nervous system penetration at craniotomy, and to examine postoperative neratinib maintenance. PATIENTS AND METHODS: Patients with HER2-positive brain metastases undergoing clinically indicated cranial resection of a parenchymal tumor received neratinib 240 mg orally once a day for 7 to 21 days preoperatively, and resumed therapy postoperatively in 28-day cycles. Exploratory evaluations of time to disease progression, survival, and correlative tissue, cerebrospinal fluid (CSF), and blood-based analyses examining neratinib concentrations were planned. The study was registered at ClinicalTrials.gov under number NCT01494662. RESULTS: We enrolled 5 patients between May 22, 2013, and October 18, 2016. As of March 1, 2019, patients had remained on the study protocol for 1 to 75+ postoperative cycles pf therapy. Two patients had grade 3 diarrhea. Evaluation of the CSF showed low concentrations of neratinib; nonetheless, 2 patients continued to receive therapy without disease progression for at least 13 cycles, with one on-study treatment lasting for nearly 6 years. Neratinib distribution in surgical tissue was variable for 1 patient, while specimens from 2 others did not produce conclusive results as a result of limited available samples. CONCLUSION: Neratinib resulted in expected rates of diarrhea in this small cohort, with 2 of 5 patients receiving the study treatment for durable periods. Although logistically challenging, we were able to test a limited number of CSF- and parenchymal-based neratinib concentrations. Our findings from resected tumor tissue in one patient revealed heterogeneity in drug distribution and tumor histopathology.

TBCRC 022: A Phase II Trial of Neratinib and Capecitabine for Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer and Brain Metastases.

PURPOSE: Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)-positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. PATIENTS AND METHODS: Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m2 twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. RESULTS: Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B).Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.

Malignant primary cardiac tumors: review of a single institution experience.

BACKGROUND: Primary cardiac sarcomas are uncommon. The authors undertook to review the Mayo Clinic's experience with primary cardiac sarcomas consisting of 34 patients seen over a 32-year period. METHODS: The patient database at the Mayo Clinic was searched to identify patients with malignant tumors of the heart seen during the 32-year period between 1975 and 2007. Thirty-four patients with primary cardiac sarcomas were identified and their medical records reviewed for details pertaining to presenting symptoms, staging modalities, treatment approaches, and outcomes. RESULTS: Of the 34 patients, 17 were men and 17 were women. The median age was 44 years. The mean duration of symptoms at the time of diagnosis was 3.6 months. The most common histologic type was angiosarcoma (41%). The median follow-up for the entire group was 12 months (range, 0-61 months). The median survival for those who underwent a complete surgical excision was 17 months compared with 6 months for those in whom a surgical complete remission could not be achieved (P = .01). Patients with angiosarcoma had a lower survival compared with patients with other histologies (5 months vs 17 months; P = .01). The median survival of patients with metastatic disease was 5 months versus 15 months in patients without metastatic disease (P = .03 by the log-rank test). CONCLUSIONS: Cardiac sarcomas remain a rare but lethal disease. Compared with extracardiac sarcomas, the prognosis for patients with cardiac sarcomas remains very poor. A complete surgical excision should be performed if possible. Innovative treatment strategies are required.

A phase I multiple dose, dose escalation study of cG250 monoclonal antibody in patients with advanced renal cell carcinoma.

The chimeric monoclonal antibody cG250 recognises the G250/CAIX/MN antigen found on 95% of clear cell renal cell carcinomas (RCCs). We performed a phase I clinical trial to evaluate the safety, blood pharmacokinetics (PK), and biodistribution of repeated doses of cG250. The primary endpoint was toxicity. Secondary endpoints were cG250 biodistribution and PK; measurement of human anti-chimeric-antibodies (HACA); and tumour response rates. Eligible patients had unresectable or metastatic clear cell RCC. Doses of 5, 10, 25, or 50 mg/m(2) were given weekly by intravenous infusion for six weeks. Three patients were treated at each dose level. Trace (131)I-labelled cG250 was administered on weeks 1 and 5. Thirteen patients participated and were evaluable. One patient developed brain metastases and was replaced. No grade 3 or 4 toxicities and no dose-limiting toxicity occurred. One patient died due to progressive disease within 30 days of receiving the study drug. One patient developed HACA during the second six-week cycle. PK analysis showed mean whole body and blood alpha and beta half-lives of cG250 of 18.99 +/- 6.84 and 180.19 +/- 86.68 hours, respectively. All patients had cG250 tumour localization by gamma camera imaging in week 1 and 5. One patient had a complete response, nine patients had stable disease, and three had progressive disease. One patient received 11 six-week cycles of treatment with no toxicity or HACA. In conclusion, repeated intravenous doses of up to 50 mg/m(2) of cG250 are safe. Furthermore cG250 has a long half-life and targets clear cell RCC effectively.

Applying quality-of-life data formally and systematically into clinical practice.

The systematic integration of quality-of-life (QOL) assessment into the clinical setting, although deemed important, infrequently occurs. Barriers include the need for a practical approach perceived as useful and efficient by patients and clinicians and the inability of clinicians to readily identify the value of integrating QOL assessments into the clinical setting. We discuss the use of QOL data in patient care and review approaches used to integrate QOL assessment into the clinical setting. Additionally, we highlight select QOL measures that have been successfully applied in the clinical setting. These measures have been shown to identify key QOL issues, improve patient-clinician communications, and improve and enhance patient care. However, the work done to date requires continued development. Continued research is needed that provides information about benefits and addresses limitations of current approaches.

Pathology, imaging, and treatment of cardiac tumours.

Cardiac tumours are a rare, but often devastating, clinical diagnosis. They encompass a broad set of lesions that include both neoplastic and non-neoplastic conditions. Cardiac tumours are often diagnosed incidentally during work-up for other conditions, or during ultrasound, CT, or MRI scans for unusual or nonspecific symptoms. In the past decade, important changes have been made in the nomenclature and the recommendations for diagnosis of cardiac tumours, as highlighted by the WHO's 2015 revision of the classification of cardiac tumours. Moreover, important advances in molecular genetics and therapeutics offer new approaches for the diagnosis and treatment of affected patients. In this Review, we provide an overview of the clinical, pathological, and imaging characteristics of all types of cardiac masses, including both benign and malignant primary cardiac neoplasms.

Efficacy of the PARP Inhibitor Veliparib with Carboplatin or as a Single Agent in Patients with Germline BRCA1- or BRCA2-Associated Metastatic Breast Cancer: California Cancer Consortium Trial NCT01149083.

Purpose: We aimed to establish the MTD of the poly (ADP-ribose) (PAR) polymerase inhibitor, veliparib, in combination with carboplatin in germline BRCA1- and BRCA2- (BRCA)-associated metastatic breast cancer (MBC), to assess the efficacy of single-agent veliparib, and of the combination treatment after progression, and to correlate PAR levels with clinical outcome.Experimental Design: Phase I patients received carboplatin (AUC of 5-6, every 21 days), with escalating doses (50-20 mg) of oral twice-daily (BID) veliparib. In a companion phase II trial, patients received single-agent veliparib (400 mg BID), and upon progression, received the combination at MTD. Peripheral blood mononuclear cell PAR and serum veliparib levels were assessed and correlated with outcome.Results: Twenty-seven phase I trial patients were evaluable. Dose-limiting toxicities were nausea, dehydration, and thrombocytopenia [MTD: veliparib 150 mg po BID and carboplatin (AUC of 5)]. Response rate (RR) was 56%; 3 patients remain in complete response (CR) beyond 3 years. Progression-free survival (PFS) and overall survival (OS) were 8.7 and 18.8 months. The PFS and OS were 5.2 and 14.5 months in the 44 patients in the phase II trial, with a 14% RR in BRCA1 (n = 22) and 36% in BRCA2 (n = 22). One of 30 patients responded to the combination therapy after progression on veliparib. Higher baseline PAR was associated with clinical benefit.Conclusions: Safety and efficacy are encouraging with veliparib alone and in combination with carboplatin in BRCA-associated MBC. Lasting CRs were observed when the combination was administered first in the phase I trial. Further investigation of PAR level association with clinical outcomes is warranted. Clin Cancer Res; 23(15); 4066-76. ©2017 AACR.

Oncologic emergencies: diagnosis and treatment.

Patients with malignancies are subject to developing a unique set of complications that require emergent evaluation and treatment. With the increasing incidence of cancer in the general population and improved survival, these emergencies will be more frequently encountered. Physicians must be able to recognize these conditions and institute appropriate therapy after a focused initial evaluation. The approach to definitive therapy is commonly multidisciplinary, involving surgeons, radiation oncologists, medical oncologists, and other medical specialists. Prompt interventions can be lifesaving and may spare patients considerable morbidity and pain. In this review, we discuss the diagnosis of and initial therapy for common emergencies in hematology and oncology.

Use of opioids in the treatment of severe pain in terminally ill patients--dying should not be painful.

Pain is a common symptom at the end of life. The vast majority of pain can be readily managed if simple principles of practice are followed. Chronic pain requires continuous analgesia, and severe pain requires use of strong analgesics, most commonly the opioids. In addition to drugs administered continually, short-acting medications must be available for "breakthrough" pain. This article reviews the principles of pain management in terminally ill patients, using a case-based demonstration.