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Antonio C Wolff

Publications and source records attributed to Antonio C Wolff.

8 recordsLinked to original sources
PubMed2026

Patient-reported outcomes from the TBCRC 022 study of neratinib and ado-trastuzumab emtansine for HER2-positive breast cancer brain metastases.

PURPOSE: In TBCRC 022 (NCT01494662), neratinib and ado-trastuzumab emtansine (T-DM1) demonstrated intracranial activity among patients with HER2-positive breast cancer brain metastases. However, gastrointestinal (GI) toxicities-particularly diarrhea-were common, potentially impacting quality of life. Clinician-reported adverse event (CTCAE) grading may underestimate the patient experience. We report GI toxicities using patient-reported outcomes (PROs) in TBCRC's neratinib-T-DM1 cohort. METHODS: Patients received neratinib (160&#x202f;mg daily) and T-DM1 (3.6&#x202f;mg/kg IV every 21 days). A pre-planned analysis assessed patient-reported GI toxicities during Cycles 1-4 using the Patient-reported Outcomes Measurement Information System (PROMIS) GI Diarrhea scale, Systemic Therapy-Induced Diarrhea Assessment Tool (STIDAT), and PRO-CTCAE. Descriptive statistics and linear mixed effects models evaluated symptom trajectories over time. We evaluated agreement for PRO and clinician-reported data. RESULTS: Forty-four patients enrolled; all completed &#x2265;1 PRO. GI symptom burden increased over Cycles 1-3. PROMIS scores worsened significantly by Cycle 2, with a peak mean increase of 6.62 (95% confidence interval (CI): 2.67-10.59; p&#x202f;=&#x202f;0.002) at Cycle 3. STIDAT scores also worsened by Cycle 3 (mean change 0.50; 95%CI: 0.11-0.90; p&#x202f;=&#x202f;0.015). Based on maximum PRO-CTCAE scores, moderate-to-severe symptoms were reported by 20.5% (diarrhea), 24.4% (appetite loss), and 41.0% (constipation). Agreement between PRO-CTCAE and clinician-reported CTCAE was low (kappa <0.2) with clinicians reporting less toxicity. PROMIS and STIDAT scores were significantly correlated. CONCLUSION: This GI-focused PRO analysis highlights the value of PROs in capturing patient-experienced toxicities that impact quality of life yet are underestimated by clinicians. Incorporating PROs into clinical trials can inform supportive care and prophylactic strategies.

Humans↗
PubMed2026

Artificial intelligence-based tumour infiltrating lymphocyte quantification in patients with triple-negative breast cancer: an independent validation study.

BACKGROUND: Tumour-infiltrating lymphocytes (TILs) are a robust prognostic marker in patients with triple-negative breast cancer. Artificial intelligence (AI)-derived computational tools assessing TILs could improve efficiency, but require independent validation against clinical outcomes. We aimed to compare the prognostic performance of AI-derived TIL scores with pathologist-scored TILs in a large, prospectively collected dataset pooled from randomised controlled trials. METHODS: CATALINA was an independent, external validation study using prospectively collected long-term clinical outcome data pooled from seven randomised clinical trials conducted at multiple sites. We independently evaluated two previously validated AI pipelines that generate five computationally assessed tumour-infiltrating lymphocyte (cTIL) scores by masked, independent deployment of locked models. cTIL scores were correlated with the mean of the pathologist-scored stromal TILs (sTILs) in 220 digitised haematoxylin and eosin whole slide images in a cohort of patients with early-stage triple-negative or HER-2 positive breast cancer, previously scored by trained pathologists in a TIL-reproducibility study. Prognostic performance was assessed in a separate cohort of patients with early triple-negative breast cancer pooled from seven prospective, randomised adjuvant trials. Multivariable Cox regression models adjusted for clinicopathological factors and study heterogeneity assessed associations of cTIL score and sTIL score with invasive disease-free survival, distant disease-free survival, and overall survival. 5-year discrimination was estimated using time-dependent area under the receiver operating characteristic curve (AUC). FINDINGS: Individual data were collated from 1759 patients, of whom 1356 had complete clinicopathological data, pathologist sTIL scores, and cTIL scores available. Modest correlation (r 0&#xb7;375-0&#xb7;473) was observed between cTIL scores and the mean pathologist sTIL score. Both sTIL and cTIL were independently associated with 5-year invasive disease-free survival, distant disease-free survival, and overall survival after adjustment for clinicopathological factors (hazard ratio for invasive disease-free survival was 0&#xb7;73 [95% CI 0&#xb7;66-0&#xb7;82]; q<0&#xb7;0001, distant disease-free survival was 0&#xb7;70 [0&#xb7;61-0&#xb7;79]; q<0&#xb7;0001, and overall survival was 0&#xb7;72 [0&#xb7;63-0&#xb7;82]; q<0&#xb7;0001 for sTIL scores and 0&#xb7;80 [0&#xb7;73-0&#xb7;89]; q<0&#xb7;0001, 0&#xb7;77 [0&#xb7;69-0&#xb7;86]; q<0&#xb7;0001, and 0&#xb7;79 [0&#xb7;70-0&#xb7;88]; q=0&#xb7;0002, respectively, for percentage_lymphocyte scores). In models adjusted for clinicopathological variables and sTIL score, cTIL score did not maintain a statistically significant prognostic association. Both sTIL and cTIL scores improved the 5-year AUC over clinicopathological variables alone, while cTIL score did not significantly further improve AUC when combined with clinicopathological variables and sTIL score. INTERPRETATION: Two cTIL models deployed entirely without retraining or modification provided statistically significant prognostic information and improved risk discrimination compared with clinicopathological variables alone in this large, platform-based, independent validation study. Although cTIL score did not incrementally improve prognostication compared with models combining clinicopathological variables with sTIL score, these findings support the application of cTILs as a reproducible prognostic biomarker, particularly in settings where routine or widespread pathologist assessment is unavailable. FUNDING: Breast Cancer Research Foundation (USA).

Humans↗
PubMed2003

Local failure and prognostic factors in ductal carcinoma in situ: concentration on recent publications.

PURPOSE OF REVIEW: Traditional therapy for ductal carcinoma in situ has been mastectomy or conservative surgery plus radiation, but interest in more expeditious therapies such as conservative surgery alone is growing. A first step in considering changes in an already successful treatment is to evaluate tumor and patient factors that may predict outcome. Identifying and understanding these prognostic factors will aid researchers in designing new treatment paradigms. The purpose of this review is to assess the value of commonly accepted potential prognostic factors in patients with ductal carcinoma in situ. RECENT FINDINGS: During this past year several retrospective studies have evaluated putative prognostic factors in ductal carcinoma in situ. We will compare these later publications with results from prospective randomized trials and one meta-analysis. SUMMARY: There does not appear to be unanimous agreement on the prognostic factors associated with increased risk of local failure in patients treated with conservative surgery and radiation for ductal carcinoma in situ. In our chosen papers, however, comedonecrosis and positive margins are most likely prognostic factors for increased local failure.

Adult↗
PubMed2003

Disposition of docosahexaenoic acid-paclitaxel, a novel taxane, in blood: in vitro and clinical pharmacokinetic studies.

PURPOSE: Docosahexaenoic acid-paclitaxel is as an inert prodrug composed of the natural fatty acid DHA covalently linked to the C2'-position of paclitaxel (M. O. Bradley et al., Clin. Cancer Res., 7: 3229-3238, 2001). Here, we examined the role of protein binding as a determinant of the pharmacokinetic behavior of DHA-paclitaxel. EXPERIMENTAL DESIGN: The blood distribution of DHA-paclitaxel was studied in vitro using equilibrium dialysis and in 23 cancer patients receiving the drug as a 2-h i.v. infusion (dose, 200-1100 mg/m(2)). RESULTS: In vitro, DHA-paclitaxel was found to bind extensively to human plasma (99.6 +/- 0.057%). The binding was concentration independent (P = 0.63), indicating a nonspecific, nonsaturable process. The fraction of unbound paclitaxel increased from 0.052 +/- 0.0018 to 0.055 +/- 0.0036 (relative increase, 6.25%; P = 0.011) with an increase in DHA-paclitaxel concentration (0-1000 microg/ml), suggesting weakly competitive drug displacement from protein-binding sites. The mean (+/- SD) area under the curve of unbound paclitaxel increased nonlinearly with dose from 0.089 +/- 0.029 microg.h/ml (at 660 mg/m(2)) to 0.624 +/- 0.216 microg.h/ml (at 1100 mg/m(2)), and was associated with the dose-limiting neutropenia in a maximum-effect model (R(2) = 0.624). A comparative analysis indicates that exposure to Cremophor EL and unbound paclitaxel after DHA-paclitaxel (at 1100 mg/m(2)) is similar to that achieved with paclitaxel on clinically relevant dose schedules. CONCLUSIONS: Extensive binding to plasma proteins may explain, in part, the unique pharmacokinetic profile of DHA-paclitaxel described previously with a small volume of distribution ( approximately 4 liters) and slow systemic clearance ( approximately 0.11 liters/h).

Adult↗
PubMed2002

Systemic therapy.

The systemic treatment of breast cancer is a moving target, reflected by the continuous update of treatment guidelines. Chemotherapy regimens, including the adjuvant role of taxanes and preoperative systemic therapy, continue to be optimized. A major challenge facing researchers and clinicians is how to improve the therapeutic index of present and future therapies, identify patients most likely to benefit from the proposed intervention, and avoid treating those who would be exposed to potential toxicities with minimal gain. Anti-estrogens are a prime example of a targeted therapy with a high therapeutic index. Data are now available on aromatase inhibitors in the adjuvant setting and pure antiestrogens in metastatic disease. The role of targeted antihuman epidermal growth factor receptor 2 therapy in the adjuvant setting is being actively investigated, but this is complicated by the inadequate standardization of human epidermal growth factor receptor 2 expression assays used in clinical practice. A long overdue revision of the breast cancer staging system becomes effective in January 2003, bringing it more in line with current standards of care and facilitating data collection for future outcome analysis of therapeutic interventions. These and other important developments since 2001 are examined in this review.

Antibodies, Monoclonal↗
PubMed2002

Preoperative therapy in breast cancer: lessons from the treatment of locally advanced disease.

The greater use of screening has changed the stage distribution of breast cancer, and an increasing number of patients are diagnosed with earlier stages of the disease. Still, locally advanced breast cancer (LABC) remains a major clinical problem in the United States and a common presentation in many parts of the world. There is no standard definition of LABC. One commonly used includes patients with large primary tumors greater than 5 cm (T3) or with skin/chest wall involvement (T4), and/or fixed axillary (N2) or ipsilateral internal mammary (N3) lymph node involvement. According to the tumor node metastasis staging, these usually include stage IIIa (T0-2N2 or T3N1-2) and stage IIIb (T4Nx or TxN3) disease. Inflammatory breast cancer (T4d) is included in most classifications despite its distinct clinical behavior and worse prognosis overall, but it serves as an example of combined modality intervention. Historically, the term LABC has been applied to those clinical presentations where the disease is considered inoperable. However, these therapeutic principles (including preoperative or primary systemic therapy [PST]) are increasingly being applied to patients presenting with tumors greater than 5 cm and negative lymph nodes (stage IIb-T3N0) or even smaller tumors, who are considered to have operable disease and a better outcome than those traditionally classified as having LABC. PST is increasingly being used in otherwise operable stage I and II patients aiming at greater rates of breast conservation and earlier efficacy assessment. This article reviews many of these issues and ongoing research questions.

Antineoplastic Agents, Hormonal↗
PubMed2002

Predicting cancer therapy-induced cardiotoxicity: the role of troponins and other markers.

Several anticancer drugs have been associated with cardiac toxicity, especially the anthracyclines and trastuzumab. The pathogenesis of anthracycline-associated toxicity has been well described, whereas the mechanism of trastuzumab-associated toxicity is unknown. Although routine cardiac imaging studies (e.g. echocardiogram or multiple gated acquisition scans) may identify subclinical evidence of myocardial dysfunction, available data do not support their routine use for monitoring asymptomatic patients undergoing cancer therapy. Other modalities such as nuclear medicine scintigraphy with indium-111-antimyosin antibody and endomyocardial biopsy have been shown to be useful in identifying early cardiac damage, but their routine use is limited by practical considerations such as feasibility and cost. Consequently, there is significant interest in developing simple and reproducible methods for identifying patients at risk for treatment-induced myocardial damage. Available data suggest that circulating markers such as troponins and natriuretic peptides could potentially be useful for this purpose. Measurement of plasma troponin levels are commonly used in clinical practice in order to provide diagnostic and prognostic information in patients with myocardial ischaemia. Elevated levels may likewise correlate with anthracycline-induced cardiac damage, although plasma levels are only minimally elevated (well below that associated with ischaemia), and elevations may persist for weeks or months after anthracycline exposure. Clinical trials are currently evaluating the role of these markers in predicting both early and late, clinical and subclinical damage associated with anthracyclines and trastuzumab.

Antibiotics, Antineoplastic↗