Measuring handicap: the London Handicap Scale, a new outcome measure for chronic disease.

OBJECTIVE--To develop a handicap measurement scale in a self completion questionnaire format, with scale weights allowing quantification of handicap at an interval level of measurement. DESIGN--Adaptation of the International Classification of Impairments, Disabilities and handicaps into a practical questionnaire incorporating the dimensions of handicap mobility, occupation, physical independence, social integration, orientation, and economic self sufficiency and scale weights derived from interviews with a general population sample, with the technique of conjoint analysis. SETTING--Two general practices in different areas of London. SUBJECTS--240 adults aged 55-74 years randomly selected from the practices, 101 (42%) of whom agreed to be interviewed, and 79 (78%) of whom completed the exercise. MAIN MEASURES--Rating of severity of handicap associated with 30 hypothetical health scenarios on a visual analogue scale, from which was derived a matrix of scale weights ("part utilities") relating to different levels of disadvantage on each dimension, with a formula for combining them into an overall handicap score. Severity scores measured directly for five scenarios not used to derive the scale weights were compared with those calculated from the formula to validate the model. RESULTS--The part utilities obtained conformed with the expected hierarchy for each dimension, confirming the validity of the method. The measured severities and those calculated from the formula for the five scenarios used to validate the model agreed closely (Pearson's r = 0.98, p = 0.0009; Kendall's tau = 1.00, p = 0.007). CONCLUSIONS--This interval level handicap measurement scale will be useful in assessing both specific therapies and health services, in clinical trials, in analyses of cost effectiveness, and in assessments of quality assurance.     

Activity of the morpholino anthracycline 3′-deamino-3′-morpholino-13-deoxo-10-hydroxycarminomycin (MX2) against human tumor colony-forming unitsin vitro

Summary In several preclinical systems, the morpholino anthracycline MX2 has greater antitumor activity than doxorubicin, is less cardiotoxic, and is effective against multidrug resistant cancer cells. We used a human tumor soft-agar cloning assay to test the cytotoxicity of MX2 against single cell suspensions from freshly obtained human tumors. Tumor cells were exposed to MX2 at 0.05 and 0.5 g/ml either for 1 hour (201 specimens; 77 [38%] assessable) or continuously (231 specimens; 91 [39%] assessable). Superior antitumor activity was observed with continuous exposure (19%in vitro response at 0.05 g/ml and 69% at 0.5 g/ml) than with 1-hour exposure (1.3% at 0.05 g/ml and 12% at 0.5 g/ml). Activity was seen against all types of cancer tested including renal (91%), melanoma (88%), ovarian (73%), breast (71%) and non-small-cell lung (67%) cancer at a MX2 concentration of 0.5 g/ml after continuous exposure. If appropriate plasma levels can be achieved in patients, MX2 could have significant clinical activity in patients with those tumors.     

Results of a phase II upfront window of pharmacokinetically guided topotecan in high-risk medulloblastoma and supratentorial primitive neuroectodermal tumor.

PURPOSE: To assess the antitumor efficacy of pharmacokinetically guided topotecan dosing in previously untreated patients with medulloblastoma and supratentorial primitive neuroectodermal tumors, and to evaluate plasma and CSF disposition of topotecan in these patients. PATIENTS AND METHODS: After maximal surgical resection, 44 children with previously untreated high-risk medulloblastoma were enrolled, of which 36 were assessable for response. The topotecan window consisted of two cycles, administered initially as a 30-minute infusion daily for 5 days, lasting 6 weeks. Pharmacokinetic studies were conducted on day 1 to attain a topotecan lactone area under the plasma concentration-time curve (AUC) of 120 to 160 ng/mL.h. After 10 patients were enrolled, the infusion was modified to 4 hours, with dosage individualization. RESULTS: Of 36 assessable patients, four patients (11.1%) had a complete response and six (16.6%) showed a partial response, and disease was stable in 17 patients (47.2%). Toxicity was mostly hematologic, with only one patient experiencing treatment delay. The target plasma AUC was achieved in 24 of 32 studies (75%) in the 30-minute infusion group, and in 58 of 93 studies (62%) in the 4-hour infusion group. The desired CSF topotecan exposure was achieved in seven of eight pharmacokinetic studies when the topotecan plasma AUC was within target range. CONCLUSION: Topotecan is an effective agent against pediatric medulloblastoma in patients who have received no therapy other than surgery. Pharmacokinetically guided dosing achieved the target plasma AUC in the majority of patients. This drug warrants testing as part of standard postradiation chemotherapeutic regimens. Furthermore, these results emphasize the importance of translational research in drug development, which in this case identified an effective drug.     

Atypical teratoid/rhabdoid tumors (ATRT): improved survival in children 3 years of age and older with radiation therapy and high-dose alkylator-based chemotherapy.

PURPOSE: To describe clinical features, therapeutic approaches, and prognostic factors in pediatric patients with atypical teratoid/rhabdoid tumors (ATRT) treated at St Jude Children's Research Hospital (SJCRH). PATIENTS AND METHODS: Primary tumor samples from patients diagnosed with ATRT at SJCRH between July 1984 and June 2003 were identified. Pathology review included histologic, immunohistochemical analysis, and fluorescence in situ hybridization for SMARCB1 (also known as hSNF5/INI1) deletion. Clinical records of patients with pathologic confirmation of ATRT were reviewed. RESULTS: Thirty-seven patients were diagnosed with ATRT at SJCRH during the 19-year study interval. Six patients were excluded from this clinical review based on pathologic or clinical criteria. Of the remaining 31 patients, 22 were younger than 3 years. Posterior fossa primary lesions and metastatic disease at diagnosis were more common in younger patients with ATRT. All patients underwent surgical resection; 30 received subsequent chemotherapy. The majority of patients aged 3 years or older received postoperative craniospinal radiation. Two-year event-free (EFS) and overall survival (OS) of children aged 3 years or older (EFS, 78% + 14%; OS, 89% +/- 11%) were significantly better than those for younger patients (EFS, 11% +/- 6%; OS, 17% +/- 8%); EFS, P = .009 and OS, P = .0001. No other clinical characteristics were predictive of survival. Three of four patients 3 years or older with progressive disease were successfully rescued with ifosfamide, carboplatin, and etoposide therapy. CONCLUSION: Children presenting with ATRT before the age of 3 years have a dismal prognosis. ATRT presenting in older patients can be cured using a combination of radiation and high-dose alkylating therapy. Older patients with relapsed ATRT can have salvage treatment using ICE chemotherapy.     

Invasive Breast Carcinoma Tumor Size on Core Needle Biopsy: Analysis of Practice Patterns and Effect on Final Pathologic Tumor Stage

Introduction

In the absence of nodal metastasis, pathologic tumor (pT) size remains one of the most important factors in adjuvant treatment decisions and patient prognosis in breast cancer. The aim of this study was to evaluate the effect of core needle biopsy (CNB) tumor size on final pT stage.

Role of 3D sonohysterography in the investigation of uterine synechiae/asherman's syndrome: Pictorial assay

Several imaging methods have been applied for evaluation of suspected uterine synechiae; however, sonohysterography is yet recognised as a valid and accurate modality. Performing three‐dimensional (3D) imaging along with sonohysterography enables evaluation of the uterus in the coronal plane to detect and grade the adhesions that characterise this condition. Thus, 3D sonohysterography is a minimally invasive and cost‐effective tool for investigating suspected synechiae and is particularly useful when the transvaginal sonography findings are normal.