Folate hydrolase-1 (FOLH1) is a novel target for antibody-based brachytherapy in Merkel cell carcinoma.

BACKGROUNDS: Folate Hydrolase-1 (FOLH1; PSMA) is a type II transmembrane protein, luminally expressed by solid tumour neo-vasculature. Monoclonal antibody (mAb), J591, is a vehicle for mAb-based brachytherapy in FOLH1+ cancers. Brachytherapy is a form of radiotherapy that involves placing a radioactive material a short distance from the target tissue (e.g., on the skin or internally); brachytherapy is commonly accomplished with the use of catheters, needles, metal seeds and antibody or small peptide conjugates. Herein, FOLH1 expression in primary (p) and metastatic (m) Merkel cell carcinoma (MCC) is characterized to determine its targeting potential for J591-brachytherapy. MATERIALS & METHODS: Paraffin sections from pMCC and mMCC were evaluated by immunohistochemistry for FOLH1. Monte Carlo simulation was performed using the physical properties of conjugated radioisotope lutetium-177. Kaplan-Meier survival curves were calculated based on patient outcome data and FOLH1 expression. RESULTS: Eighty-one MCC tumours were evaluated. 67% (54/81) of all cases, 77% (24/31) pMCC and 60% (30/50) mMCC tumours were FOLH1+. Monte Carlo simulation showed highly localized ionizing tracks of electrons emitted from the targeted neo-vessel. 42% (34/81) of patients with FOLH1+/- MCC had available survival data f or analysis. No significant differences in our limited data set were detected based on FOLH1 status (p = 0.4718; p = 0.6470), staining intensity score (p = 0.6966; p = 0.9841) or by grouping staining intensity scores (- and + vs. ++, +++, +++) (p = 0.8022; p = 0.8496) for MCC-specific survival or recurrence free survival, respectively. CONCLUSIONS: We report the first evidence of prevalent FOLH1 expression within MCC-associated neo-vessels, in 60-77% of patients in a large MCC cohort. Given this data, and the need for alternatives to immune therapies it is appropriate to explore the safety and efficacy o f FOLH1-targeted brachytherapy for MCC.

Health-related quality of life in cutaneous T-cell lymphoma: A cross-sectional survey study.

Background: Patients with cutaneous T-cell lymphoma (CTCL) often have indolent but symptomatic disease. Objective: Assessment of the health-related quality of life (HRQoL) of patients with CTCL. Methods: Cross-sectional survey study. HRQoL was measured by Skindex-16 and FACT-G. Results: A total of 372 responses were received; 80 incomplete/ineligible responses were excluded. A majority of respondents identified as white (87%; 250/288) and female (67%; 193/286) with a mean age of 57 ± 14 years. Most patients had early-stage (IA-IIA) (74%; 162/203) mycosis fungoides (87%; 241/279). There were 33 (12%; 33/279) patients with Sézary syndrome. Mean itch score (visual analogue scale; VAS) was 3.2 ± 2.8, overall; 2.7 ± 2.6 for early, and 4.2 ± 2.9 for advanced disease (p = 0.008). Thirty-eight percent (108/284) and 24% (69/284) reported head/neck and groin/genital involvement, respectively.Overall HRQoL was 46 ± 27 (Skindex-16) and 71 ± 19 (FACT-G), with worse HRQoL for patients with advanced versus early disease (Skindex-16: 67 vs. 40; p=<0.001, FACT-G: 62 vs. 76; p = 0.001). Predictors of worse HRQoL included head/neck, hand/foot or groin/genital involvement, younger age and spending >15 min daily treating CTCL. Limitations: Include anonymous survey methodology, underrepresentation of certain CTCL subtypes and non-white respondents. Conclusions: Patients with CTCL, particularly those with advanced disease or involvement of the head/neck, acral or groin/genital sites, experience significant impact on HRQoL.

High somatostatin receptor expression and efficacy of somatostatin analogues in patients with metastatic Merkel cell carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive, high-grade, cutaneous neuroendocrine tumour (NET). Agents blocking programmed death 1/programmed death ligand 1 have efficacy in metastatic MCC (mMCC), but half of patients do not derive durable benefit. Somatostatin analogues (SSAs) are commonly used to treat low- and moderate-grade NETs that express somatostatin receptors (SSTRs). OBJECTIVES: To assess SSTR expression and the efficacy of SSAs in mMCC, a high-grade NET. Methods In this retrospective study of 40 patients with mMCC, SSTR expression was assessed radiologically by somatostatin receptor scintigraphy (SRS; n = 39) and/or immunohistochemically when feasible (n = 9). Nineteen patients (18 had SRS uptake in MCC tumours) were treated with SSA. Disease control was defined as progression-free survival (PFS) of ≥ 120 days after initiation of SSA. RESULTS: Thirty-three of 39 patients (85%) had some degree (low 52%, moderate 23%, high 10%) of SRS uptake. Of 19 patients treated with SSA, seven had a response-evaluable target lesion; three of these seven patients (43%) experienced disease control, with a median PFS of 237 days (range 152-358). Twelve of 19 patients did not have a response-evaluable lesion due to antecedent radiation; five of these 12 (42%) experienced disease control (median PFS of 429 days, range 143-1757). The degree of SSTR expression (determined by SRS and/or immunohistochemistry) did not correlate significantly with the efficacy endpoints. CONCLUSIONS: In contrast to other high-grade NETs, mMCC tumours appear frequently to express SSTRs. SSAs can lead to clinically meaningful disease control with minimal side-effects. Targeting of SSTRs using SSA or other novel approaches should be explored further for mMCC.

Opinions, hopes and concerns regarding pharmacogenomics: a comparison of healthy individuals, heart failure patients and heart transplant recipients.

It is not yet known whether healthy individuals and patients with a chronic disease have similar attitudes towards pharmacogenomics. Thus we conducted a survey of 175 healthy volunteers, 175 heart failure (HF) patients and 100 heart transplant recipients to compare their opinions on this subject. Most participants (>90%) stated that they would accept pharmacogenomic testing and expressed high hopes regarding its potential applications. Overall, interest for pharmacogenomics was shared equally among the three groups. In contrast, after adjusting for age, gender, education and income, healthy individuals were more likely to voice concerns about potential employment (P=0.008 vs HF, odds ratio (OR)=2.93, confidence interval (CI)=1.33-6.47; P=0.010 vs Transplant, OR=2.46, CI=1.24-4.90) and insurance discrimination (P=0.001 vs HF, OR=5.58, CI=2.01-15.48; P<0.001 vs Transplant, OR=4.98, CI=2.03-12.21) and were possibly more worried by confidentiality issues. These findings highlight the need for strict legislation and proper educational strategies directed at the general population to facilitate the clinical implementation of pharmacogenomics.

Modifying the PACT model: preserving critical elements.

Few agencies have the resources to replicate the Program for Assertive Community Treatment (PACT) model pioneered in Madison, Wisconsin, which calls for around-the-clock, comprehensive treatment and rehabilitation services for persons with serious mental illness. Most agencies modify the model program, and little is known about patient outcomes in such altered programs. This paper discusses issues in modifying the PACT model, especially for use in rural areas. The authors focus on six basic elements of the PACT model: multiservice teams, 24-hour service availability, small caseloads that do not vary in composition, ongoing and continuous services, assertive outreach, and in vivo rehabilitation. They describe how programs in South Carolina that are adaptations of the PACT model have retained these elements and achieved desired outcomes with smaller teams operating on modified schedules.

The response of an assertive community treatment program following a natural disaster.

A newly forming model treatment program for seriously mentally ill adults was dramatically affected by a natural disaster in September 1989. Hurricane Hugo rendered the offices of the Assertive Community Treatment Program uninhabitable, its vehicles marginally driveable, and its resources virtually nonexistent. In the three months following the storm, however, not a single psychiatric rehospitalization took place. Although the authors cannot claim that the program model was solely responsible for this outcome, this paper illustrates the service system elements that contributed to the program's effectiveness in the wake of one of the nation's most severe natural disasters.

Providing assertive community treatment for severely mentally ill patients in a rural area.

OBJECTIVE: The authors' goals were to describe an assertive community treatment program developed for patients in rural South Carolina and to evaluate the effect of the program on rates of hospital utilization and cost of care. METHODS: Twenty-three patients with chronic psychotic disorders living in rural areas of South Carolina were assigned to an assertive community treatment program. The patients' average number of days per year in the hospital, length of stay per admission, number of admissions per year, and estimated annual cost of care during the five years before assignment to the program and during a period from four to 26 months after assignment were compared. RESULTS: The intervention was associated with a 79 percent decrease in hospital days per year, a 64 percent decrease in the number of admissions per year, a 75 percent decrease in the average length of stay per admission, and a 52 percent reduction in estimated direct cost of care. CONCLUSIONS: Although the methods of assertive community treatment may need to be modified to suit the travel requirements and other characteristics of rural settings, the study results suggest that the model can be successfully used in rural areas.