Factors associated with psychological distress amongst outpatient chemotherapy patients: An analysis of depression, anxiety and stress using the DASS-21.

AIM: This study sought to identify clinical, demographic and service-related factors associated with psychological distress amongst outpatient chemotherapy patients. BACKGROUND: Distress in cancer patients leads to increased risk of psychological comorbidity, contributing to sub-optimal treatment adherence and potentially leading to poorer health outcomes. Screening and recognition of distress and risk factors is an important aspect of holistic care within a multidisciplinary team environment. METHODS: Data were obtained via survey and chart review of ambulatory chemotherapy patients at three public tertiary referral hospitals in Perth, Western Australia. The DASS-21 was used to screen for psychological distress. Regression analyses were used to assess the relationship between distress and a range of cancer, socioeconomic and treatment factors. RESULTS: Patients with a Karnofsky Performance Score≤80 (OR 3.8, 95% CI [1.7, 78.7]) and average waiting time (between oncology outpatient appointment and commencement of chemotherapy infusion) >60min (OR 2.4, 95% CI [1.04, 5.5]) were at increased risk of moderate-severe distress. Patients with a household income between $AU 50-75,000 p.a. had a lower risk of distress compared to <$25,000 p.a. (OR 0.05, 95% CI [0.01, 0.52]). On sub-scale analysis, depression and anxiety contributed more to overall distress than the stress subscales. CONCLUSIONS: Performance status, waiting times and household income were key predictors of distress. Findings could assist clinicians to identify higher-risk population subsets that could benefit from targeted screening and additional psychological and social work support. Findings could also assist administrators to consider the contribution of modifiable factors such as waiting times to patient distress.

A phase 1b clinical trial optimizing regulatory T cell depletion in combination with platinum-based chemotherapy in thoracic cancers.

Background: Single-agent cyclophosphamide can deplete regulatory T-cells (Treg). We aimed to determine optimal dosing and scheduling of oral cyclophosphamide, alongside pemetrexed-based chemotherapy, to deplete Treg in mesothelioma or non-small-cell lung cancer patients.Methods: 31 Patients received pemetrexed ± cisplatin or carboplatin on day 1 of a 21-day cycle (maximum 6 cycles). From cycle two, patients received cyclophosphamide, 50 mg/day, with intrapatient escalation to maximum 100/150 mg/day alternately. Immunological changes were examined by flow cytometry. Primary endpoint was Treg proportion of CD4+ T-cells, with doses tailored to target Treg nadir <4%.Results: Reduction in Treg proportion was observed on day 8 of all cycles, and was not augmented by cyclophosphamide. Few patients achieved the <4% Treg target. Treg proliferation reached nadir one week after chemotherapy, and peaked on day 1 of the subsequent cycle. Efficacy parameters were similar to chemotherapy alone. Seventeen percent of patients ceased cyclophosphamide due to toxicity.Conclusions: Specific Treg depletion to the degree seen with single-agent cyclophosphamide was not observed during pemetrexed-based chemotherapy. This study highlights the poor evidence basis for use of cyclophosphamide as an immunotherapeutic in combination with chemotherapy, and the importance of detailed flow cytometry studies.Trial registration: Clinical trial registration: www.anzctr.org.au identifier is ACTRN12609000260224.

What Matters to Potential Patients in Chemotherapy Service Delivery? A Discrete Choice Experiment.

INTRODUCTION: Designing and funding chemotherapy care to meet patient expectations is challenging. Issues including convenience, outcomes, cost, and continuity of care are all potentially important and the appropriate trade-off between them is not clear. Regions with significant geographic spread and concentration of care in metropolitan areas pose a particular problem as ensuring low-cost convenient care is potentially difficult. However, the relative value of different aspects of chemotherapy are as yet unknown. The objective of this work is to quantify the relative value of different aspects of chemotherapy service delivery in an older Australian general population sample. METHODS: A discrete choice experiment was administered in an older Australian general population sample without cancer. The survey approach asks a series of hypothetical choice tasks and allows estimation of the relative value of different aspects of care. Analysis considered the average respondent, and then also explored the level of preference divergence across the population. RESULTS: One thousand and sixty-two individuals provided data and were included in the analysis. There was a strong population preference for home-based chemotherapy, for follow-up by a specialist, for psycho-social support, and for low cost care. CONCLUSION: These strong population preferences should be considered when designing chemotherapy care. This poses a significant challenge, both logistically and financially. However, this information can help policy makers identify the components of good value care.

Patients prefer chemotherapy on the same day as their medical oncology outpatient appointment.

PURPOSE: Numerous oncology units have separated outpatient appointments and chemotherapy delivery to another day (TOD) to improve efficiency. This survey assessed patient preferences for scheduling medical oncology outpatient appointments and chemotherapy delivery for either treatment delivered on the same day as the outpatient appointment (TSD) or TOD. PATIENTS AND METHODS: Patients (N = 198) from two major metropolitan tertiary centers in Perth-Sir Charles Gairdner Hospital (n = 110) and Royal Perth Hospital (n = 88)-completed surveys from April 15 to May 24, 2013. Eligibility criteria included any adult patient with cancer receiving an intravenous chemotherapy or targeted agent who had completed ≥ two cycles of treatment or attended ≥ two chemotherapy appointments on a concurrent chemoradiotherapy program. RESULTS: The majority of patients preferred TSD (85%) versus TOD. Convenience (50%) and distance or difficulty in transportation to hospital (25%) were the most common reasons for TSD preference. Current treatment schedule (odds ratio [OR], 59.2; 95% CI, 18.7 to 265.2) was significantly associated with treatment schedule preference. Younger age (58.3 v 65.2 years; P = .01) and presence of household dependents (OR, 4.2; 95% CI, 1.2 to 27.1) were also associated with TSD preference. Scheduling preference was not influenced by time prepared to wait for chemotherapy (χ(2) (2) = 3.86; P = .14), with 44% and 39% of patients willing to wait up to 60 and 120 minutes, respectively. Almost all patients preferred chemotherapy delivery before 2 pm (99%). CONCLUSION: Patients preferred to receive chemotherapy on the same day as their medical oncology outpatient appointment. Morning delivery of chemotherapy was preferred. Meeting patients' expectations will present significant challenges to efficient service provision as caseloads increase.

Optimization of response classification criteria for patients with malignant pleural mesothelioma.

INTRODUCTION: Response-assessment metrics play an important role in clinical trials and routine patient management. For patients with malignant pleural mesothelioma (MPM), the standard for response assessment is image-based measurements of tumor thickness made according to the modified RECIST (Response Evaluation Criteria in Solid Tumors) protocol. To classify tumor response, changes in tumor thickness are compared with the standard RECIST -30% and +20% cutoffs for partial response (PR) and progressive disease (PD), respectively, which are not specific to MPM. The purpose of this work is to optimize the correlation between tumor response and patient survival by assessing the validity of existing response criteria in MPM and proposing alternative criteria. METHODS: Computed tomography measurements of tumor thickness were acquired at baseline and throughout treatment for 78 patients undergoing standard-of-care chemotherapy. Overall survival was correlated with best response and first follow-up response using Harrell's C statistic. The response criteria for PD and PR were each varied in 1% increments to obtain optimized classification criteria. The performance was cross-validated using a leave-one-out approach. RESULTS: Median survival was 14.9 months. The performance of the standard RECIST criteria in correlating response with survival was C=0.778, whereas the optimized performance of C=0.855 was obtained with criteria of -64% for PR and +50% for PD. After cross-validation, this performance was slightly reduced to C=0.829. CONCLUSIONS: Optimized tumor-response classification criteria were obtained for patients with MPM. These criteria improve the correlation between image-based response and patient survival.

A phase II study of intermittent sunitinib malate as second-line therapy in progressive malignant pleural mesothelioma.

INTRODUCTION: There is no accepted second-line therapy for patients with advanced malignant pleural mesothelioma (MPM), whose disease has progressed after first-line chemotherapy. The multitargeted tyrosine kinase inhibitor sunitinib malate targets several pathways overexpressed in mesothelioma. This phase II study assessed objective response to sunitinib and correlative biomarkers in patients with progressive pretreated MPM. METHODS: Eligible patients had confirmed MPM, radiological progression after chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 1, and measurable disease. Patients received oral sunitinib 50 mg daily for 28 of every 42 days. The primary endpoint was objective radiological response. Patients without prior pleurodesis had fluorodeoxyglucose positron emission tomographic response assessed by total glycolytic volume criteria. Correlative biomarkers included serum mesothelin, vascular endothelial growth factor (VEGF)-A, VEGF-C, interleukin-8, sVEGFR-2, sVEGFR-3, and s-kit. RESULTS: Fifty-three patients received sunitinib between July 2006 and December 2009; 51 were assessable for response. Patients received a median of two cycles (range, 1-12); 40% required dose reduction. Fatigue was the most prominent toxicity. Six patients (12%) had a confirmed radiological partial response, 34 (65%) had stable disease, and 11 (22%) had progressive disease as best response. Six of 20 patients had a decrease in fluorodeoxyglucose positron emission tomographic total glycolytic volume of 15% or more. Median overall survival was 6.1 months, and median time to progression was 3.5 months. Correlative biomarkers did not predict treatment response. CONCLUSIONS: Sunitinib has activity in a subset of patients with pretreated MPM. Consideration should be given to different treatment schedules and examination of other biomarkers for further study of sunitinib in MPM.

Classification and toxicities of vascular disrupting agents.

Vascular disrupting agents (VDAs) are an exciting new group of targeted therapies under active clinical research in many solid tumors, in particular, lung cancer. Small-molecule VDAs are the focus of current clinical research, and consist of the flavonoids and the tubulin-binding agents. Toxicities of single-agent VDAs are characterized by acute, transient, and generally noncumulative side effects including headaches, nausea and vomiting, tumor pain, hypertension, and tachycardia. Flavonoid agents can also cause infusion site pain, visual disturbances, electrocardiac abnormalities, and symptoms consistent with an acute release of serotonin. Tubulin-binding agents can result in cardiac ischemia, abdominal pain, neuromotor abnormalities and cerebellar ataxia, and acute hemodynamic changes. Clinical trials investigating VDAs in combination with traditional chemotherapy have also shown the potential for significant pharmacologic and adverse toxicity interactions. Further research will need to focus on pharmacokinetic and pharmacodynamic parameters to optimize dosing schedules, determine effective combinations with chemotherapy, and minimize toxicities associated with VDAs.

Audit of patients with mesothelioma treated with pemetrexed in a single institution in Western Australia.

Malignant pleural mesothelioma (MPM) is a devastating malignancy that until recently has had no effective treatment. Pemetrexed in combination with cisplatin entered routine clinical practice following reports of efficacy in 2003. We performed a retrospective analysis of all patients with malignant mesothelioma at a single institution treated with pemetrexed in any combination or as monotherapy between 2004 and 2007. During this period, 62 patients received pemetrexed-based chemotherapy for MPM, most of whom were male (87%), treated in the palliative setting (84%) and received pemetrexed in combination with a platinum agent (95%). Pemetrexed was found to be well tolerated and produced clinical benefit and response rates similar to other published studies for its use in MPM in the phase IV or community practice settings. Patients with progressive disease as their best radiological response had very poor outcomes, while patients with stable disease had similar outcomes to those with responses. We confirmed that survival after commencement of pemetrexed-based chemotherapy remains under one year in this group of patients, somewhat less than the survival reported in phase III trials that currently inform clinical decision making. Further research is required to identify those patients who might benefit from pemetrexed based on molecular predictive markers.

Bilateral thoracoscopy, mediastinoscopy and laparoscopy, in addition to CT, MRI and PET imaging, are essential to correctly stage and treat patients with mesothelioma prior to trimodality therapy.

BACKGROUND: Trimodality therapy (TMT; extrapleural pneumonectomy (EPP), chemotherapy and radiation therapy) offers the potential of optimal survival in selected patients with Brigham stage I-II epitheliod mesothelioma based on CT, MRI and PET scanning. We hypothesized that these scanning modalities were inadequate to accurately stage these patients. METHODS: Patients suitable for TMT, in addition to CT, MRI and PET scanning, prior to EPP, underwent bilateral thoracoscopy, mediastinoscopy and laparoscopy (surgical staging). Follow-up CT scans were performed, six monthly, quality of life assessments yearly. RESULTS: From 1 June 2004 to 28 February 2007, 34 patients were referred; mean age was 66 years (range: 44-69). Surgical staging was performed in 30 patients; 24 patients were confirmed as Brigham Stage I-II. However, six were upstaged, five as stage IV disease (one contralateral chest, two contralateral chest and abdomen, two abdomen) and one as mediastinal node positive; two further patients were reclassified histologically (one sarcomatoid, one biphasic). These eight patients fared poorly, 50% dying within 1 year from mesothelioma. Following surgical staging, 3 patients declined further surgery; thus, 19 patients proceeded to surgery, 3 were unresectable and 16 received EPP. Follow-up of all 34 patients is complete. CONCLUSION: Surgical staging identified 26% of patients who would have received no benefit from TMT.

Outcome for patients with malignant pleural mesothelioma referred for Trimodality therapy in Western Australia.

INTRODUCTION: Trimodality therapy (TMT), consisting of extrapleural pneumonectomy (EPP), preoperative or postoperative combination chemotherapy, and high-dose hemithoracic radiotherapy, is the only therapy reported to achieve long-term survival in selected patients with malignant pleural mesothelioma (MPM). Thus, TMT was introduced as an option for such patients in Western Australia in 2004. However, TMT has never been compared with non-TMT therapy in the same patient population, thereby introducing a potential for selection bias. METHOD: We performed a retrospective review of all patients referred for TMT consisting of EPP, adjuvant chemotherapy, and hemithoracic radiotherapy at a quaternary referral institution. Patient eligibility for referral for TMT was based on patients' tolerability for pneumonectomy, epithelioid subtype, and computed tomography and positron emission tomography scanning indicating operable disease, with the exclusion of extrapleural lymphadenopathy and metastatic disease (clinical stage T1-3N0-1M0). Eligible patients consenting to TMT also underwent a surgical staging procedure (bilateral thoracoscopy, mediastinoscopy, and laparoscopy) to confirm eligibility before EPP. RESULTS: Thirty-six patients have been referred for TMT since 2004, and there has been a median of 27 months follow-up; of 31 patients having surgical staging, eight were ineligible for EPP and one declined EPP. Of the 22 planned for EPP, 18 underwent EPP and four had unresectable disease at surgery. There was one death in hospital six days post-EPP and another death postdischarge and 28 days post-EPP (30-day mortality 11%); 15 of 16 EPP survivors received adjuvant chemotherapy and 14 completed adjuvant radiotherapy. Pathologic analysis of the 18 resected EPP specimens revealed N2 disease in seven patients (39%) and nonepithelioid subtype in six patients (33%). Local recurrence did not occur among EPP survivors; however, 56% (9 of 16 patients) developed distant recurrence. Median and 1-year survival did not differ between the 18 EPP patients and 18 non-EPP patients (20.4 versus 20.7 months and 76 versus 78%, respectively; p = NS). DISCUSSION: In this case series, we could not demonstrate a survival benefit for patients in the EPP group compared with that in the non-EPP group. After surgical staging, 26% of patients were ineligible for TMT. Thus, surgical staging is essential before proceeding with EPP. Despite aggressive imaging and surgical staging, 39% of patients will have N2 disease and 18% will have unresectable disease at operation. Although complete locoregional control was achieved with TMT, distant recurrence affected most EPP survivors despite careful patient selection and a high rate of completion of adjuvant therapy. We conclude that TMT for operable epithelioid MPM requires further assessment in randomized controlled trials.