Multi-Institutional Validation of a Mammography-Based Breast Cancer Risk Model.

PURPOSE: Accurate risk assessment is essential for the success of population screening programs in breast cancer. Models with high sensitivity and specificity would enable programs to target more elaborate screening efforts to high-risk populations, while minimizing overtreatment for the rest. Artificial intelligence (AI)-based risk models have demonstrated a significant advance over risk models used today in clinical practice. However, the responsible deployment of novel AI requires careful validation across diverse populations. To this end, we validate our AI-based model, Mirai, across globally diverse screening populations. METHODS: We collected screening mammograms and pathology-confirmed breast cancer outcomes from Massachusetts General Hospital, USA; Novant, USA; Emory, USA; Maccabi-Assuta, Israel; Karolinska, Sweden; Chang Gung Memorial Hospital, Taiwan; and Barretos, Brazil. We evaluated Uno's concordance index for Mirai in predicting risk of breast cancer at one to five years from the mammogram. RESULTS: A total of 128,793 mammograms from 62,185 patients were collected across the seven sites, of which 3,815 were followed by a cancer diagnosis within 5 years. Mirai obtained concordance indices of 0.75 (95% CI, 0.72 to 0.78), 0.75 (95% CI, 0.70 to 0.80), 0.77 (95% CI, 0.75 to 0.79), 0.77 (95% CI, 0.73 to 0.81), 0.81 (95% CI, 0.79 to 0.82), 0.79 (95% CI, 0.76 to 0.83), and 0.84 (95% CI, 0.81 to 0.88) at Massachusetts General Hospital, Novant, Emory, Maccabi-Assuta, Karolinska, Chang Gung Memorial Hospital, and Barretos, respectively. CONCLUSION: Mirai, a mammography-based risk model, maintained its accuracy across globally diverse test sets from seven hospitals across five countries. This is the broadest validation to date of an AI-based breast cancer model and suggests that the technology can offer broad and equitable improvements in care.

Cytotoxic potential of selected medicinal plants in northeast Brazil.

BACKGROUND: Great biodiversity is a highlight of Brazilian flora. In contrast, the therapeutic potentialities of most species used in folk medicine remain unknown. Several of these species are commonly used to treat cancer. In this study, we investigated the cytotoxic activity of 18 plants from 16 families that are found in the northeast region of Brazil. METHODS: The following species were studied: Byrsonima sericea DC. (Malpighiaceae), Cupania impressinervia Acev. Rodr. var. (revoluta) Radlk (Sapindaceae), Duranta repens Linn. (Verbenaceae), Helicostylis tomentosa (Poepp. & Endl) Rusby (Moraceae), Himatanthus bracteatus (A.DC.) Woodson (Apocynaceae), Ipomoea purga (Wender.) Hayne (Convolvulaceae), Ixora coccinea Linn. (Rubiaceae), Mabea piriri Aubl. (Euphorbiaceae), Miconia minutiflora (Melastomataceae), Momordica charantia L. (Cucurbitaceae), Ocotea glomerata (Nees) Mez (Lauraceae), Ocotea longifolia Kunth (Oreodaphne opifera Mart. Nees) (Lauraceae), Pavonia fruticosa (Mill.) Fawc. & Rendle (Malvaceae), Psychotria capitata Ruiz & Pav. (Rubiaceae), Schefflera morototoni (Aubl.) Maguire, Steyerm. & Frodin (Araliaceae), Solanum paludosum Moric. (Solanaceae), Xylopia frutescens Aubl. (Annonaceae) and Zanthoxylum rhoifolium Lam. (Rutaceae). Their dried leaves, stems, flowers or fruits were submitted to different solvent extractions, resulting in 55 extracts. After incubating for 72 h, the cytotoxicity of each extract was tested against tumor cell lines using the alamar blue assay. RESULTS: The B. sericea, D. repens, H. bracteatus, I. purga, I. coccinea, M. piriri, O. longifolia and P. capitata extracts demonstrated the most potent cytotoxic activity. The chloroform soluble fractions of D. repens flowers and the hexane extract of I. coccinea flowers led to the isolation of quercetin and a mixture of α- and ß-amyrin, respectively, and quercetin showed moderate cytotoxic activity. CONCLUSION: The B. sericea, D. repens, H. bracteatus, I. purga, I. coccinea, M. piriri, O. longifolia and P. capitata plants were identified as having potent cytotoxic effects. Further investigations are required to determine the mechanisms of cytotoxicity exhibited and their in vivo activities. This work reinforces the need to understand the therapeutics potentialities of Brazilian medicinal plants.

Development and validation of a nomogram to estimate the risk of prostate cancer in Brazil.

AIM: To develop and validate a nomogram to estimate the probability of prostate cancer (PCa) in men undergoing opportunistic screening. PATIENTS AND METHODS: This was a cross-sectional observational study on a cohort of men screened for PCa at the Barretos Cancer Hospital (BCH) between January 2004 and December 2007. Patients' data were collected from their charts and binary logistic regression analyses were performed to assess the power of various factor combinations as predictors of the PCa risk. RESULTS: Out of the 1,313 screened men who underwent prostate biopsy, 553 (42.1%) had histopathological confirmation of PCa. The logistic regression analyses provided an area under the receiver operating characteristics (ROC) curve (AUC) of 0.737 (95% confidence interval (CI)=0.678-0.796) for the best predictor combination. A nomogram was constructed to estimate the individual risk for PCa prior to biopsy. CONCLUSION: Our nomogram provides an easy and practical method, superior in performance to the traditional criteria, predicting the diagnosis of PCa with a reasonable accuracy.

Comparison of clinical and pathologic findings of prostate cancers detected through screening versus conventional referral in Brazil.

INTRODUCTION: Data regarding prostate cancer screening in Brazil are limited. We compared features of prostate cancers detected through screening versus those referred for treatment in Brazil. PATIENTS AND METHODS: Group I included 500 of 13,754 men whose cancers were detected through screening, and Group II included 2731 men referred for treatment through the habitual public health system. We used Mann-Whitney and χ(2) tests to compare clinical and pathologic findings, considering significant any P < 0.05. RESULTS: Median prostate-specific antigen (PSA) was lower among screened patients (5.5 ng/mL versus 10.0 ng/mL; P < 0.001). Of the screened patients, 170 (34%) had biopsy Gleason score ≥ 7, compared with 1265 (46.3%) in the referred group (P < 0.001). Lymph node metastases were suspected in 8.6% of the referred versus 3.2% of the screened men (P = 0.002). Distant metastases were more common in the referred men (9.3% vs. 3.0%; P < 0.001). Only 6.0% of the screened cancers were locally advanced at diagnosis (T3 or T4) versus 26.5% of the referred (P < 0.001). Screened patients had a higher proportion of localized tumors after surgery (67.7% vs. 54.2%; P = 0.002). Pathology Gleason scores were also lower among screened men (P < 0.01). Lymphadenectomies were performed in 166/636 men (26.1%). No nodal metastases were found in screened cancers (0/28; 0.0%), while 6/138 referred cancers (4.3%) presented nodal involvement (P = 0.3). CONCLUSION: Clinical and pathologic characteristics of screen-detected cancers are more favorable than those of tumors diagnosed through the Brazilian health system.

Opportunistic screening for skin cancer using a mobile unit in Brazil.

BACKGROUND: Skin cancer is the most common malignancy in the white population worldwide. In Brazil, the National Cancer Institute (INCA) estimates that in 2010 there will be 119,780 and 5,930 new cases of non-melanoma skin cancer and melanoma, respectively. The aim of this study was to evaluate the use of a mobile unit in the diagnosis and treatment of skin cancer in several poor regions of Brazil. METHODS: The diagnosis of skin cancer was accomplished through active medical screening in the prevention Mobile Unit (MU) of Barretos Cancer Hospital (BCH). The study population consisted of patients examined in the MU between 2004 and 2007, and their suspicious lesions were subjected to histopathological evaluation. Data were collected prospectively from standardized forms and analyzed. RESULTS: During the screening, 17,857 consultations were carried out. A total of 2012 (11.2%) cases of skin cancer were diagnosed. The predominant histological type reported was basal cell carcinoma (n = 1,642 or 81.6%), followed by squamous cell carcinoma (n = 303 or 15.1%), Bowen's disease (n = 25 or 1.2%), malignant melanoma (n = 23 or 1.1%), basosquamous cell carcinoma (n = 3 or 0.1%), miscellaneous lesions (12 or 0.6%), and metatypical carcinoma (n = 4 or 0.2%). Only 0.6% of lesions were stage III. There were no stage IV non-melanoma skin lesions, as well as no melanomas stages III and IV, found. CONCLUSIONS: It was observed that the MU can be a useful tool for early skin cancer diagnosis and treatment. This program probably is important, especially in developing countries with inadequate public health systems and social inequality.

Determination of the phenolic content and antioxidant potential of crude extracts and isolated compounds from leaves of Cordia multispicata and Tournefortia bicolor.

In this work, the total phenolic content and antioxidant activity of extracts and four flavonoids isolated from leaves of two Boraginaceae species (Cordia multispicata Cham. and Tournefortia bicolor Sw.) were evaluated using Folin-Ciocalteu reagent, DPPH free radical scavenging and inhibition of peroxidation of linoleic acid by FTC method. For comparison, ascorbic acid, alpha-tocopherol and BHT were used. In general, extracts from T. bicolor (68.8 +/- 0.001 to > 1000 mg/g) showed higher phenolic content than C. multispicata (66.1 +/- 0.009 to 231 +/- 0.07 mg/g), and also scavenged radicals (IC(50) 12.8 +/- 2.5 to 437 +/- 3.5 mg/L) and inhibited lipid peroxide formation (IC(50) 51.2 +/- 2.29 to 89 +/- 0.59 mg/L). For these extracts a good correlation between the phenolic content and antioxidant activity was observed, suggesting that T. bicolor is richer in phenolic compounds and that it could serve as a new source of natural antioxidants or nutraceuticals with potential applications. Chromatographic procedures monitored by antioxidant assays afforded seven compounds, which were identified by spectral analyses (IR, MS and 1D and 2D NMR) and comparison with reported data as being trans-phytol (1), taraxerol (2), 3,7,4'-trimethoxyflavone (3), 5,3'-dihydroxy-3,7,4'-trimethoxyflavone (4), quercetin (5), tiliroside (6), and rutin (7). Compounds (4-7) were also evaluated and were effective as DPPH quenching (IC(50) 7.7 +/- 3.6 to 79.3 +/- 3.4 mg/L) and as inhibition of lipid peroxidation (IC(50) 80.1 +/- 0.98 to 88.7 +/- 3.62 mg/L). This is the first report on the total phenolic content, radical-scavenging and antioxidant activities of these species.

Program for prostate cancer screening using a mobile unit: results from Brazil.

OBJECTIVES: To evaluate the initial results of a prostate cancer screening program using mobile units in Brazil. METHODS: Since 2004, we have conducted a program of prostate cancer screening using mobile units across 231 municipalities from 6 Brazilian states. RESULTS: A total of 17 571 men were evaluated by clinical history, digital rectal examination (DRE), and serum free and total prostate-specific antigen (PSA) levels. The recommendations for biopsy were a PSA level of ≥ 4.0 ng/mL, DRE findings suspicious for cancer, or a PSA level of 2.5-4.0 ng/mL with a percent-free PSA level < 15%. The biopsy protocol included 12 biopsy cores from the peripheral zone, 2 from the transition zone, and additional sampling of suspicious areas. The cumulative cancer detection rate was 3.7%. The main indication for biopsy was a PSA level of ≥ 4.0 ng/mL (51.2%), with a positive predictive value (PPV) of 44.1%. Another 19.7% of biopsied men had suspicious DRE findings with a normal PSA level (PPV 23.5%). A percent-free PSA level of < 15% in men with a PSA level of 2.5-4.0 ng/mL and normal DRE findings yielded a PPV of 31.1%. The PPV was greater (70.9%) for the 7.1% of men with both suspicious DRE findings and a PSA level of ≥ 4.0 ng/mL. Most cancers were Stage T1-T2 (93.4%), and the percentage of Gleason score of ≥ 7 was 32.5%. The proportion of insignificant cancers according to Epstein's criteria was 13.5%. CONCLUSIONS: A mobile prostate cancer screening unit enabled an underserved population to gain access to specialized care through the public healthcare system. The cancer detection rate in this population was similar to those from international studies.