RESULTS OF EXTERNAL BEAM RADIOTHERAPY IN 448 PATIENTS WITH CLINICALLY LOCALIZED ADENOCARCINOMA OF THE PROSTATE

The results of external beam radiotherapy for clinically localized adenocarcinorna of the prostate in 448 patients treated in the period 1980–90 were reviewed. The average follow up was 4.9 years. The patients were aged 44–87 years (median 69 years) and all had histopathological evidence of adenocarcinoma by needle biopsy or transurethral resection of prostate. The histopathological grading was: 127 G₁; 154 G₂; 127 G₃; 12 G₄; 28 G_x. Clinical staging according to TNM (American Urological Association) was: 29 T₀ (A2); 4 T₁ (B1); 173 T₂ (B2); 176 T₃ (C1); 63 T₄ (C2); 3 T_x. Routine surgical pelvic lymph node staging was not performed but patients had radiological (computerized tomography scan or lymphogram) nodal staging: 350 N₀; 22 N₁; 12 N₂; 64 N_x. High energy linear accelerator external beam radiotherapy was given by multiple fields to total doses of 50–70 Gy (median 60 Gy). The majority of patients (307, 69%) was treated by a uniform policy under the care of one radiation oncologist (HM). The rates of local and distant failure at 5 years were 10% (s.e. = 2%) and 42% (s.e. = 3%), respectively. The late complication rate at 5 years was 25% (s.e. = 2%), comprising mild 16%, moderate 7% and severe 1.3%. The 5 year overall survival rate was 64% (s.e. = 2%) and the cancer-specific survival rate was 74% (s.e. = 3%). Both histological grade and clinical stage were strongly predictive of overall survival and distant failure. Only histological grade was predictive of local failure. Treatment with external beam radiotherapy for this common cancer resulted in survival and disease control rates that compare favourably with other published radiotherapy series and has been accompanied by acceptably low morbidity.     

Measurement of mesothelioma on thoracic CT scans: a comparison of manual and computer-assisted techniques

Our purpose in this study was to evaluate the variability of manual mesothelioma tumor thickness measurements in computed tomography (CT) scans and to assess the relative performance of six computerized measurement algorithms. The CT scans of 22 patients with malignant pleural mesothelioma were collected. In each scan, an initial observer identified up to three sites in each of three CT sections at which tumor thickness measurements were to be made. At each site, five observers manually measured tumor thickness through a computer interface. Three observers repeated these measurements during three separate sessions. Inter- and intra-observer variability in the manual measurement of tumor thickness was assessed. Six automated measurement algorithms were developed based on the geometric relationship between a specified measurement site and the automatically extracted lung regions. Computer-generated measurements were compared with manual measurements. The tumor thickness measurements of different observers were highly correlated (r > or = 0.99); however, the 95% limits of agreement for relative inter-observer difference spanned a range of 30%. Tumor thickness measurements generated by the computer algorithms also correlated highly with the average of observer measurements (r > or = 0.93). We have developed computerized techniques for the measurement of mesothelioma tumor thickness in CT scans. These techniques achieved varying levels of agreement with measurements made by human observers.     

Mindfulness-based interventions for eating disorders: The potential to mobilize multiple associative-learning change mechanisms

Mindfulness is a two-component skill that includes mindful awareness (attentional monitoring of present moment experience) and mindful acceptance (adopting an attitude of acceptance toward this experience). Although mindfulness-based interventions (MBIs) are efficacious for many conditions, there is a lack of research on MBIs for eating disorders (EDs). We propose that MBIs may be promising for EDs given their potential to mobilize not one, but multiple associative-learning change mechanisms in EDs–defined as adaptive processes of change involving one of two forms of associative-learning: Pavlovian and operant learning. We hypothesize how MBIs–via increasing either mindful awareness or mindful acceptance–may mobilize up to eight associative-learning change mechanisms, two involving Pavlovian learning, and six involving operant learning. We also elaborate on similarities and differences between MBIs and CBT approaches for EDs, as well as opportunities for synergy. Finally, we present recommendations for future research related to the development and evaluation of novel MBI interventions for EDs and the testing of mechanisms and patient-treatment matching hypotheses.     

Phase II study of pemetrexed with and without folic acid and vitamin B12 as front-line therapy in malignant pleural mesothelioma.

PURPOSE: This phase II clinical study evaluated the efficacy of pemetrexed for the treatment of malignant pleural mesothelioma (MPM). PATIENTS AND METHODS: Patients with a histologically proven diagnosis of MPM, chemotherapy-naive measurable lesions, and adequate organ function received pemetrexed (500 mg/m2) intravenously over 10 minutes every 3 weeks. After a protocol change, most patients also received folic acid and vitamin B12 supplementation to improve safety. RESULTS: A total of 64 patients were enrolled. Nine (14.1%) of the 64 patients had a partial response. The Kaplan-Meier estimate for median overall survival was 10.7 months. Forty-three patients received vitamin supplementation for all courses of therapy, and 21 patients did not. Seven of the nine responders were vitamin supplemented. The median overall survival was 13.0 months for supplemented patients and 8.0 months for nonsupplemented patients. Vitamin-supplemented patients completed more cycles of therapy than nonsupplemented patients (median, six v two cycles, respectively). Grade 3/4 neutropenia (23.4%) and grade 3/4 leukopenia (18.8%) were the most common laboratory toxicities. Fatigue and febrile neutropenia were the most commonly reported nonlaboratory events (grade 3, 6.3%; grade 4, 0.0% each). The incidence of these toxicities was generally lower in the supplemented patients. CONCLUSION: Single-agent pemetrexed for MPM resulted in a moderate response rate (14.1%) and median overall survival of 10.7 months. Patients supplemented with folic acid and vitamin B12 tolerated treatment better (less toxicity and more cycles of treatment) and had a 5-month greater median overall survival than nonsupplemented patients. These results indicate that patients with MPM could benefit from single-agent pemetrexed treatment combined with vitamin supplementation.     

Plasma levels of angiopoietin-2, VEGF-A,and VCAM-1 as markers of bevacizumab-induced hypertension: CALGB 80303 and 90401 (Alliance)

Hypertension is a common toxicity induced by bevacizumab and other antiangiogenic drugs. There are no biomarkers to predict the risk of bevacizumab-induced hypertension. This study aimed to identify plasma proteins related to the function of the vasculature to predict the risk of severe bevacizumab-induced hypertension. Using pretreated plasma samples from 398 bevacizumab-treated patients in two clinical trials (CALGB 80303 and 90401), the levels of 17 proteins were measured via ELISA. The association between proteins and grade 3 bevacizumab-induced hypertension was performed by calculating the odds ratio (OR) from logistic regression adjusting for age, sex, and clinical trial. Using the optimal cut-point of each protein, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for hypertension were estimated. Five proteins showed no difference in levels between clinical trials and were used for analyses. Lower levels of angiopoietin-2 (p?=?0.0013, OR 3.41, 95% CI 1.67–7.55), VEGF-A (p?=?0.0008, OR 4.25, 95% CI 1.93–10.72), and VCAM-1 (p?=?0.0067, OR 2.68, 95% CI 1.34–5.63) were associated with an increased risk of grade 3 hypertension. The multivariable model suggests independent effects of angiopoietin-2 (p?=?0.0111, OR 2.71, 95% CI 1.29–6.10), VEGF-A (p?=?0.0051, OR 3.66, 95% CI 1.54–9.73), and VCAM-1 (p?=?0.0308, OR 2.27, 95% CI 1.10–4.92). The presence of low levels of 2–3 proteins had an OR of 10.06 (95% CI 3.92–34.18, p?=?1.80?×?10^–5) for the risk of hypertension, with sensitivity of 89.7%, specificity of 53.5%, PPV of 17.3%, and NPV of 97.9%. This is the first study providing evidence of plasma proteins with potential value to predict patients at risk of developing bevacizumab-induced hypertension.

Clinical trial registration: ClinicalTrials.gov Identifier: NCT00088894 (CALGB 80303); and NCT00110214 (CALGB 90401).

     

Colorectal Polyps in Carriers of the APC I1307K Polymorphism

PURPOSE The probability of colorectal cancer is moderately increased among carriers of the APC I1307K polymorphism. However, it is not known if endoscopic surveillance of this high-risk group is warranted. The prevalence of polyps and adenomas in specimens of colorectal cancer who are carriers and noncarriers of the APC I1307K polymorphism is compared. METHOD Prevalence of adenomatous polyps in the pathology specimens of the study participants, stratified by their APC I1307K polymorphism status, was studied in 900 consecutive cases of colorectal cancer diagnosed in northern Israel between 1998 and 2002, within the framework of a population-based, case-controlled study (MECC Study). RESULTS The APC I1307K mutation was detected in 78 colorectal cancer cases (8.7 percent) of the study population. Prevalence was higher among Ashkenazi Jews (11.2 percent) than among non-Ashkenazi Jews (2.7 percent) or Arabs (3.1 percent). After adjustment for age, APC I1307K carriers were significantly more likely than noncarriers to have polyps in their surgical specimen (51.3 percent vs. 32.6 percent, P = 0.002). Adenomas with a tubular component (either tubular adenomas or tubulovillous adenomas), but not villous adenomas, were significantly more frequent among carriers (37.2 percent vs. 23.6 percent, P = 0.005). CONCLUSION Together with former evidence of I1307K being a risk factor for colorectal cancer, these data suggest that colonoscopic surveillance for colorectal adenomas and cancer may be warranted in I1307K carriers, even in the absence of other identifiable risk factors. Supported by the National Institutes of Health grant RO1-CA81488 to S.B.G. and G.R.     

Trigeminal trophic syndrome

Ulceration of the nose may be inadvertently induced by the patient. Although trigeminal trophic syndrome is an uncommon cause of chronic ulcers, healthcare providers should consider the possibility of this disorder when encountering a patient with nasal ulcerations. Trigeminal trophic syndrome most commonly occurs in older women following therapy for trigeminal neuralgia. The ulcers usually involve the nasal ala and paranasal areas. The clinical vignette of a man with a self-induced nasal ulcer secondary to trigeminal trophic syndrome, which was initially suspected to be skin cancer, is presented. Since nasal ulcerations can be secondary to other conditions, a lesional biopsy should be performed to exclude other diagnoses when trigeminal trophic syndrome is entertained. In addition to trigeminal trophic syndrome, the differential diagnosis of conditions that can cause nasal ulcers include factitial disorders with self-induced ulcerations (such as dermatitis artifacta and neurotic excoriations), granulomatous conditions, infectious diseases, malignancy, and pyoderma gangrenosum. Treatment of trigeminal trophic syndrome requires prevention of digital manipulation of the lesion-either by occluding contact with the ulcer, initiating psychotropic medication, or both. Psychiatric and/or pharmacologic intervention should be considered to reduce or resolve further habitual self-inflicted injury before surgical intervention.