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.

The impact of arm lymphedema on healthcare utilization during long-term breast cancer survivorship: a population-based cohort study.

PURPOSE: Cancer treatment-related late effects degrade survivors' quality of life, independence, and societal integration, yet may be ameliorated, or even reversed, with effective care. Unfortunately, survivors inconsistently receive this care and the impact on their healthcare utilization is unknown. We sought to estimate differences in utilization between breast cancer (BC) survivors with and without upper extremity lymphedema; a common, remediable late effect. METHODS: We conducted a population-based, retrospective longitudinal cohort study of survivors with incident BC diagnosed from January 1, 1990, through December 31, 2010. HC utilization was characterized using the Berenson-Eggers Type of Service (BETOS) categories. Outcomes included overall healthcare utilization as well as its compartmentalization into the BETOS categories of (1) Evaluation and management, (2) Procedures, (3) Imaging, (4) Tests, (5) Durable medical equipment, (6) Physical/occupational therapy, (7) Other, and (8) Exceptions/Unclassified. RESULTS: The cohort included 1906 subjects of which 94% (1800) had records meeting the inclusion criteria. Mean follow-up per survivor was 12.8 years (mean, 11, range 1-25 years). Analysis revealed that (1) survivors with BC-associated lymphedema used > 30% more services annually; (2) their increased utilization lessened but persisted for at least 10 years after diagnosis; and (3) this finding of increased utilization extends across all BETOS categories, is further amplified as BMI increases, and cannot be explained solely by lymphedema-directed care. CONCLUSIONS: BC-related lymphedema appears to be an important driver of survivors' healthcare utilization and guideline-concordant activities to reduce its incidence and severity may be cost neutral or saving. IMPLICATIONS FOR CANCER SURVIVORS: Early detection and effective management of cancer-related late effects like lymphedema may reduce survivors' healthcare needs in the decades that follow their cancer treatment.

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.

Effect of Collaborative Telerehabilitation on Functional Impairment and Pain Among Patients With Advanced-Stage Cancer: A Randomized Clinical Trial.

IMPORTANCE: Most patients with advanced-stage cancer develop impairment and pain-driven functional losses that jeopardize their independence. OBJECTIVE: To determine whether collaborative telerehabilitation and pharmacological pain management improve function, lessen pain, and reduce requirements for inpatient care. DESIGN, SETTING, AND PATIENTS: The Collaborative Care to Preserve Performance in Cancer (COPE) study was a 3-arm randomized clinical trial conducted at 3 academic medical centers within 1 health care system. Patient recruitment began in March 2013 and follow-up concluded in October 2016. Participants (N = 516) were low-level community or household ambulators with stage IIIC or IV solid or hematologic cancer. INTERVENTIONS: Participants were randomly assigned to the (1) control arm, (2) telerehabilitation arm, or (3) telerehabilitation with pharmacological pain management arm. All patients underwent automated function and pain monitoring with data reporting to their care teams. Participants in arms 2 and 3 received 6 months of centralized telerehabilitation provided by a physical therapist-physician team. Those in arm 3 also received nurse-coordinated pharmacological pain management. MAIN OUTCOMES AND MEASURES: Blinded assessment of function using the Activity Measure for Postacute Care computer adaptive test, pain interference and average intensity using the Brief Pain Inventory, and quality of life using the EQ-5D-3L was performed at baseline and months 3 and 6. Hospitalizations and discharges to postacute care facilities were recorded. RESULTS: The study included 516 participants (257 women and 259 men; mean [SD] age, 65.6 [11.1] years), with 172 randomized to 1 of 3 arms. Compared with the control group, the telerehabilitation arm 2 had improved function (difference, 1.3; 95% CI, 0.08-2.35; P = .03) and quality of life (difference, 0.04; 95% CI, 0.004-0.071; P = .01), while both telerehabilitation arms 2 and 3 had reduced pain interference (arm 2, -0.4; 95% CI, -0.78 to -0.09; P = .01 and arm 3, -0.4; 95% CI, -0.79 to -0.10; P = .01), and average intensity (arm 2, -0.4; 95% CI, -0.78 to -0.07; P = .02 and arm 3, -0.5; 95% CI, -0.84 to -0.11; P = .006). Telerehabilitation was associated with higher odds of home discharge in arms 2 (odds ratio [OR], 4.3; 95% CI, 1.3-14.3; P = .02) and 3 (OR, 3.8; 95% CI, 1.1-12.4; P = .03) and fewer days in the hospital in arm 2 (difference, -3.9 days; 95% CI, -2.4 to -4.6; P = .01). CONCLUSIONS AND RELEVANCE: Collaborative telerehabilitation modestly improved function and pain, while decreasing hospital length of stay and the requirement for postacute care, but these outcomes were not enhanced with the addition of pharmacological pain management. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01721343.

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.

The rationale, design, and methods of a randomized, controlled trial to evaluate the effectiveness of collaborative telecare in preserving function among patients with late stage cancer and hematologic conditions.

Disablement affects over 40% of patients with advanced stage cancer, devastates their quality of life (QoL), and increases their healthcare costs. Proactively treating the causes of disablement; physical impairments, pain, and immobility, can prolong functional independence, improve QoL and, potentially, reduce utilization. However rehabilitation service delivery models are reactive in nature and focus on catastrophic rather than incipient disability. A validated collaborative approach, the Three Component Model (TCM), optimizes important clinical outcomes and may provide an ideal framework to overcome barriers to proactively integrating rehabilitation into cancer care. A novel expansion of the TCM that targets disablement by engaging local physical therapists to address physical impairments and immobility, the TCM-Rehabilitation Services (TCM-RS), benefits and is well received by patients. However, its effectiveness has not been rigorously assessed. The 3-arm randomized COllaborative Care to Preserve PErformance in Cancer (COPE) Trial compared: 1) enhanced usual care, 2) rehabilitation services targeting physical impairments and immobility via the TCM-RS, and 3) TCM-RS plus conventional TCM pain management TCM-RS+Pain. Of the 516 participants, those randomized to arms 2 and 3 underwent an initial 4-week intervention period and were then followed for 6months with remote monitoring and monthly telephone calls. The trial's primary outcome, functional status, and secondary outcomes were assessed at baseline, 3, and 6months. Utilization was abstracted from clinical records. By estimating the effectiveness and cost-utility implications of the TCM-RS and TCM-RS+Pain, COPE will inform future delivery research, practice and policy in the means to reduce disablement in chronically diseased populations.

A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or III PIK3CA-Mutant ER-Positive and HER2-Negative Breast Cancer.

Purpose: Hyperactivation of AKT is common and associated with endocrine resistance in estrogen receptor-positive (ER+) breast cancer. The allosteric pan-AKT inhibitor MK-2206 induced apoptosis in PIK3CA-mutant ER+ breast cancer under estrogen-deprived condition in preclinical studies. This neoadjuvant phase II trial was therefore conducted to test the hypothesis that adding MK-2206 to anastrozole induces pathologic complete response (pCR) in PIK3CA mutant ER+ breast cancer.Experimental Design: Potential eligible patients with clinical stage II/III ER+/HER2- breast cancer were preregistered and received anastrozole (goserelin if premenopausal) for 28 days in cycle 0 pending tumor PIK3CA sequencing. Patients positive for PIK3CA mutation in the tumor were eligible to start MK-2206 (150 mg orally weekly, with prophylactic prednisone) on cycle 1 day 2 (C1D2) and to receive a maximum of four 28-day cycles of combination therapy before surgery. Serial biopsies were collected at preregistration, C1D1 and C1D17.Results: Fifty-one patients preregistered and 16 of 22 with PIK3CA-mutant tumors received study drug. Three patients went off study due to C1D17 Ki67 >10% (n = 2) and toxicity (n = 1). Thirteen patients completed neoadjuvant therapy followed by surgery. No pCRs were observed. Rash was common. MK-2206 did not further suppress cell proliferation and did not induce apoptosis on C1D17 biopsies. Although AKT phosphorylation was reduced, PRAS40 phosphorylation at C1D17 after MK-2206 persisted. One patient acquired an ESR1 mutation at surgery.Conclusions: MK-2206 is unlikely to add to the efficacy of anastrozole alone in PIK3CA-mutant ER+ breast cancer and should not be studied further in the target patient population. Clin Cancer Res; 23(22); 6823-32. ©2017 AACR.

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.

NeoPalAna: Neoadjuvant Palbociclib, a Cyclin-Dependent Kinase 4/6 Inhibitor, and Anastrozole for Clinical Stage 2 or 3 Estrogen Receptor-Positive Breast Cancer.

Purpose: Cyclin-dependent kinase (CDK) 4/6 drives cell proliferation in estrogen receptor-positive (ER+) breast cancer. This single-arm phase II neoadjuvant trial (NeoPalAna) assessed the antiproliferative activity of the CDK4/6 inhibitor palbociclib in primary breast cancer as a prelude to adjuvant studies.Experimental Design: Eligible patients with clinical stage II/III ER+/HER2- breast cancer received anastrozole 1 mg daily for 4 weeks (cycle 0; with goserelin if premenopausal), followed by adding palbociclib (125 mg daily on days 1-21) on cycle 1 day 1 (C1D1) for four 28-day cycles unless C1D15 Ki67 > 10%, in which case patients went off study due to inadequate response. Anastrozole was continued until surgery, which occurred 3 to 5 weeks after palbociclib exposure. Later patients received additional 10 to 12 days of palbociclib (Cycle 5) immediately before surgery. Serial biopsies at baseline, C1D1, C1D15, and surgery were analyzed for Ki67, gene expression, and mutation profiles. The primary endpoint was complete cell cycle arrest (CCCA: central Ki67 ≤ 2.7%).Results: Fifty patients enrolled. The CCCA rate was significantly higher after adding palbociclib to anastrozole (C1D15 87% vs. C1D1 26%, P < 0.001). Palbociclib enhanced cell-cycle control over anastrozole monotherapy regardless of luminal subtype (A vs. B) and PIK3CA status with activity observed across a broad range of clinicopathologic and mutation profiles. Ki67 recovery at surgery following palbociclib washout was suppressed by cycle 5 palbociclib. Resistance was associated with nonluminal subtypes and persistent E2F-target gene expression.Conclusions: Palbociclib is an active antiproliferative agent for early-stage breast cancer resistant to anastrozole; however, prolonged administration may be necessary to maintain its effect. Clin Cancer Res; 23(15); 4055-65. ©2017 AACR.

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.

Phase 1 study of sorafenib in combination with bortezomib in patients with advanced malignancies.

BACKGROUND: Sorafenib (a VEGFR and multi-targeted kinase inhibitor) and Bortezomib (a proteasome inhibitor) have clinical antineoplastic activities as single agents, and combine synergistically in preclinical models. METHODS: This Phase I study was undertaken to define the toxicity and the maximum tolerated doses (MTD) of the combination in patients with advanced solid tumors. Patients with cytologic or histologic proof of unresectable solid tumors were treated with escalating doses of sorafenib (twice daily) and bortezomib (days 1, 4, 8 and 11 intravenously) with 21-day cycles. RESULTS: Fourteen patients (7 males, median age 65, range 24-74), with renal (3), lung (3), pancreas (2), and breast, adrenal gland, melanoma, spindle cell tumor, chronic lymphocytic leukemia and multiple myeloma (1 each) were enrolled. All patients are off treatment, 10 due to disease progression. DLT was seen in two patients (one grade 3 abdominal pain and grade 4 lipase elevation; one with grade 3 vomiting) at sorafenib 200 mg twice daily and bortezomib 1.3 mg/m(2), establishing the MTD. No grade 4 hematologic or grade 5 toxicities were seen. One patient with renal cell cancer had a partial response and 5 patients attained stable disease. CONCLUSIONS: The combination of sorafenib and bortezomib was tolerated well. The recommended phase 2 doses are sorafenib 200 mg twice daily continuously with bortezomib 1 mg/m(2) on days 1, 4, 8, 11 (21 day cycles). The combination shows preliminary signs of efficacy, supporting phase 2 studies.

A phase I trial of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer.

The mammalian target of rapamycin (mTOR) plays a critical role in promoting tumor cell growth and is frequently activated in breast cancer. In preclinical studies, the antitumor activity of mTOR inhibitors is attenuated by feedback up-regulation of AKT mediated in part by Insulin-like growth factor type 1 receptor (IGF-1R). We designed a phase I trial to determine the maximum-tolerated dose (MTD) and pharmacodynamic effects of the IGF-1R antibody Cixutumumab in combination with temsirolimus in patients with metastatic breast cancer refractory to standard therapies. A 3 + 3 Phase I design was chosen. Temsirolimus and Cixutumumab were administered intravenously on days 1, 8, 15, and 22 of a 4-week cycle. Of the 26 patients enrolled, four did not complete cycle 1 because of disease progression (n = 3) or comorbid condition (n = 1) and were replaced. The MTD was determined from the remaining 22 patients, aged 34-72 (median 48) years. Most patients (86 %) had estrogen receptor positive cancer. The median number of prior chemotherapy regimens for metastatic disease was 3. The MTD was determined to be Cixutumumab 4 mg/kg and temsirolimus 15 mg weekly. Dose-limiting toxicities (DLTs) included mucositis, neutropenia, and thrombocytopenia. Other adverse events included grade 1/2 fatigue, anemia, and hyperglycemia. No objective responses were observed, but four patients experienced stable disease that lasted for at least 4 months. Compared with baseline, there was a significant increase in the serum levels of IGF-1 (p < 0.001) and IGFBP-3 (p = 0.019) on day 2. Compared with day 2, there were significant increases in the serum levels of IGF-1 (p < 0.001), IGF-2 (p = 0.001), and IGFBP-3 (p = 0.019) on day 8. A phase II study in women with metastatic breast cancer is ongoing.

End-of-life care in a population-based cohort of cancer patients: clinical trial participation versus standard of care.

OBJECTIVES: To evaluate end-of-life care in a cohort of oncology patients in Olmsted County, Minnesota, USA, and compare differences between patients participating in clinical trials and those not in clinical trials. METHODS: A population-based cohort of subjects with active oncological disease who died between 2000 and 2002 was constructed retrospectively using institutional databases. Clinical trial participation and care during the last 2 months of life were analysed. RESULTS: A total of 395 eligible patients were identified. In the 2 months prior to death, 94 (24%) patients received chemotherapy, 232 (59%) were hospitalised, 249 (63%) were in hospice and 315 (80%) had a do not resuscitate (DNR) code status. Only 8 (2%) patients received cardiopulmonary resuscitation (CPR) and 26 (7%) patients participated in a clinical trial. Patients in clinical trials were more likely to receive chemotherapy (69.2% vs 20.6%; p<0.001), undergo intubation/mechanical ventilation (15.4% vs 5.4%; p=0.040) and less likely to have DNR code status (50.0% vs 81.8%; p<0.001) when compared with patients not in clinical trials. However, no differences in hospice enrolment, days in hospice, days in the hospital, CPR or location of death were noted. CONCLUSIONS: Although opportunities for improvement exist, high quality end-of-life care was found in this study of patients with active malignancy. A majority (over 60%) of patients enrolled in hospice prior to death, 80% had a DNR status and only 2% received CPR. Although clinical trial participants received more aggressive treatments during the last 2 months of life, they did not appear to have lower quality end-of-life care.