Correlation between response to neoadjuvant chemotherapy and survival in locally advanced breast cancer patients.

BACKGROUND: Measurement of residual disease following neoadjuvant chemotherapy that accurately predicts long-term survival in locally advanced breast cancer (LABC) is an essential requirement for clinical trials development. Several methods to assess tumor response have been described. However, the agreement between methods and correlation with survival in independent cohorts has not been reported. PATIENTS AND METHODS: We report survival and tumor response according to the measurement of residual breast cancer burden (RCB), the Miller and Payne classification and the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, in 151 LABC patients. Kappa Cohen's coefficient (К) was used to test the agreement between methods. We assessed the correlation between the treatment outcome and overall survival (OS) and relapse-free survival (RFS) by calculating Harrell's C-statistic (c). RESULTS: The agreement between Miller and Payne classification and RCB classes was very high (К = 0.82). In contrast, we found a moderate-to-fair agreement between the Miller and Payne classification and RECIST criteria (К = 0.52) and RCB classes and RECIST criteria (К = 0.38). The adjusted C-statistic to predict OS for RCB index (0.77) and RCB classes (0.75) was superior to that of RECIST criteria (0.69) (P = 0.007 and P = 0.035, respectively). Also, RCB index (c = 0.71), RCB classes (c = 0.71) and Miller and Payne classification (c = 0.67) predicted better RFS than RECIST criteria (c = 0.61) (P = 0.005, P = 0.006 and P = 0.028, respectively). CONCLUSIONS: The pathological assessment of tumor response might provide stronger prognostic information in LABC patients.

Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study.

BACKGROUND: Luminal breast cancer is a highly endocrine responsive disease. However, the therapeutic benefit of chemotherapy (CT) in this population is not fully characterized. This study investigates the value of CT and hormone therapy (HT) in luminal breast cancer patients in the neoadjuvant setting. PATIENTS AND METHODS: Patients with operable breast cancer and immunophenotypically defined luminal disease (ER+/PR+/HER2-/cytokeratin 8/18+) were recruited. Patients were randomized to CT (epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) 4 cycles followed by docetaxel 100 mg/m(2 )4 cycles [EC-T]) or HT (exemestane 25 mg daily 24 weeks [combined with goserelin in premenopausal patients]). The primary end point was the clinical response measured by magnetic resonance imaging. RESULTS: Ninety-five patients were randomized (47 CT, 48 HT). The clinical response rate was 66% for CT and 48% for HT (P = 0.075). We performed an unplanned analysis based on Ki67 levels (cut-off of 10%). Similar clinical response was seen between arms in patients with low Ki67 (CT: 63%, HT: 58%; P = 0.74); patients with high Ki67 had a better response with CT (67 versus 42%; P = 0.075). Grade 3/4 toxicity was more frequent with CT. CONCLUSIONS: Luminal immunophenotype is not enough to identify patients who do not benefit from neoadjuvant CT. Luminal patients with low proliferation index could potentially avoid CT.

Genomic predictors of response to doxorubicin versus docetaxel in primary breast cancer.

UNLABELLED: Taxanes and anthracyclines improve the outcome of early breast cancer, although the benefit is limited to a small proportion of patients and are toxic. We prospectively looked for predictors of response to these drugs. EXPERIMENTAL DESIGN: Four cycles of doxorubicin (75 mg/m²) or docetaxel (100 mg/m²) were compared as presurgical chemotherapy for breast cancer. Biomarkers were determined by immunohistochemistry and fluorescent in situ hybridization using prechemotherapy core biopsies. Tumors were also classified into one of the molecular intrinsic subtypes using an immunohistochemical panel of five biomarkers and genomic profiles. Single genes and intrinsic subtypes were correlated with response to doxorubicin versus docetaxel. Among the 204 evaluable patients, significant predictors of sensitivity in multivariate analysis were low topo2a expression and ER-negative status for doxorubicin and small tumor size and ER-negative status for docetaxel. Predictors of resistance in multivariate analysis were triple-negative status (ER/PgR/HER2 negative by IHC/FISH) for doxorubicin, and high TNM stage for docetaxel. Triple-negative tumors were associated with topo2a overexpression more than the other subtypes. In 94 patients with gene expression profiles, docetaxel was superior to doxorubicin in the basal-like subtype (good pathological response rate - PCR + class I of 56 vs. 0%; P = 0.034); no significant differences were observed in the other subtypes when comparing these two drugs. Low topo2a expression and ER-negative status were predictors of response to doxorubicin, while small tumor size and ER-negative status predicted response to docetaxel. Docetaxel was superior to doxorubicin in triple-negative/basal-like tumors, while no significant differences were seen in the remaining intrinsic subtypes.

C4D immunostaining in surveillance endomyocardial biopsies from well-functioning heart allografts.

OBJECTIVE: The meaning of biopsy C4d detection in heart allografts without dysfunction or morphologic changes suggesting antibody-mediated rejection (AMR) is not clear. The aim of this study was to search for an association between C4d detection in allograft biopsies of well-functioning hearts without changes suggestive of AMR, and clinical outcomes. METHODS: Endomyocardial protocol biopsies from 44 heart transplant patients with well-functioning grafts and without changes suggesting AMR were performed at 1 month and 1 year after transplantation and analyze the presence of C4d deposition using immunohistochemistry. Two-year follow-up was based on clinical parameters and echocardiographic information. Heart graft function was categorized as good vs. poor. The presence of C4d, using diverse schemes to graduate the extension of the deposition, was correlated with clinical graft outcomes. RESULTS: C4d deposition was observed in the capillary walls of 33 biopsies (37.5%; n = 25 patients; 56.8%). No biopsy had diffuse (>50%) immunostaining. Six patients presented with multifocal capillary C4d immunostaining in at least 1 biopsy. Capillary positivity for C4d (if focal or multifocal) showed no statistical association with cellular rejection or graft function. Perimyocytic C4d detection was neither associated with rejection nor graft outcome. CONCLUSION: Our work failed to demonstrate an association between C4d detection in protocol biopsies of heart grafts and clinical outcomes. The clinical utility of C4d staining in solid organ transplantation may vary by organ. Our results suggest that C4d did not have clinical utility in surveillance biopsies of well-functioning heart grafts without morphological changes suggesting AMR.

Cuirasse skin metastases secondary to gastric adenocarcinoma.

Skin metastases are infrequent manifestations of solid tumours. However, it is important to recognize them since they may be the first evidence of a neoplasia, or a sign of tumour progression or recurrence. Skin metastases from gastric adenocarcinomas are particularly rare, and represent 6% of the total in males and 1% in females. We report, here, the case of a patient diagnosed with gastric adenocarcinoma with extensive subcutaneous infiltration of the abdominal wall, resulting in an abdominal cuirass.

Cuirasse skin metastases secondary to gastric adenocarcinoma

No disponible

Pinning of tumoral growth by enhancement of the immune response.

Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor. The neutrophils hindered cell surface diffusion so much that they induced new dynamics compatible with the slower quenched-disorder Edwards-Wilkinson universality class. Important clinical effects were also seen, including remarkably high tumor necrosis (around 80%-90% of the tumor), a general increase in survival time [the death ratio in the control group is 15.76 times higher than in the treated group (equivalent to a Cox's model hazard ratio of 0.85; 95% confidence interval 0.76-0.95, p=0.004)], and even the total elimination of some tumors.

Correlación clínico-citohistológica de los quistes congénitos cervicales. Discusión / Clinical-cytohistological correlation of cervicofacial congenital cysts. Discussion

No disponible

Diagnóstico por PET de una recidiva única en un paciente con carcinoma epidermoide de pulmón estadio I previamente resecado / PET diagnosis of an isolated relapse in a patient with a previously resected stage I epidermoid carcinoma of the lung

Propósito: Descripción de un caso de recidiva única mediastínica adenopática diagnosticada por PET de carcinoma epidermoide de pulmón estadio I. Material y métodos: Varón de 70 años, intervenido quirúrgicamente de carcinoma epidermoide de pulmón estadio I, presentando tras 28 meses, recidiva ganglionar única subcarinal, confirmada por PET y tratada con quimioterapia con reducción del 50 por ciento tras 2 ciclos de quimioterapia. Resultados: Se realiza una revisión de la literatura orientada a determinar los factores pronósticos moleculares en cáncer de pulmón no de células pequeñas en estadios precoces y a valorar la utilidad de la tomografía por emisión de positrones (PET-FDG) en el diagnóstico de enfermedad recurrente. Conclusiones: Aunque el PET-FDG puede ayudar en el diagnóstico de las recaídas locales asintomáticas, no se conocen aún las consecuencias del tratamiento precoz de las mismas ni la repercusión en la supervivencia o el pronóstico final. La determinación del grado de proliferación celular con Ki 67 y c-erb2 realizados inicialmente podrían aportar información acerca de las posibilidades de respuesta a la quimioterapia (AU)

[Usefulness of PSA-complex in the diagnosis of prostatic carcinoma]. / Utilidad del PSA-complex en el diagnóstico del carcinoma de próstata.

OBJECTIVE: Since its discovery as a marker for prostate cancer, there have been many attempts to enhance the diagnostic efficacy of the prostate specific antigen (PSA). Among these are the studies that analyze the behavior of different forms of serum PSA bound to different antiproteases, such as alpha-1-antichymotrypsin, which forms the complexed PSA (PSA-c). This study analyzed the utility of PSA-c to enhance specificity without altering sensitivity in comparison to total PSA (PSA-t). METHODS: From September 1998 to March 1999, blood samples were obtained from 96 patients that had undergone a prostate biopsy due to a suspicion of prostate cancer. PSA-c, PSA-t (Technicon Immunol system, Bayer) and PSA-c/PSA-t ratio were analyzed in these patients. RESULTS: ROC curves were plotted and the optimal cutoffs were found for which the specificity was higher for PSA-c (44.6% [CI 95%, 32-57]) versus PSA-t (35.4% [CI 95%, 25-49]) and the PSA-c/PSA-t ratio (38.5% [CI 95%, 27-51]) while maintaining a similar sensitivity index (90%). PSA-c showed similar results for other values of sensitivity. CONCLUSIONS: PSA-c was found to improve specificity in comparison to PSA-t and PSA-c/PSA-t ratio. PSA-c determination could avoid unnecessary biopsies without altering sensitivity; i.e., the same number of prostate cancers will be detected.

[Usefulness of p53 oncoprotein immunohistochemistry in the follow-up of bladder carcinoma: a 5-year study]. / Utilidad de la oncoproteína p53-IHQ en el seguimiento del carcinoma vesical: estudio a 5 años.

OBJECTIVE: Mutations in the TP53 gene are frequently detected in some types of malignant tumors (bladder, prostate, kidney, lungs, breast, colon and rectum). This study analyzed the utility of semi-quantitative determination of p53 in transitional cell carcinoma of the bladder by an immunohistochemical technique and evaluated the results at 5 years. METHODS/RESULTS: A prospective clinical cohort study was conducted on 81 patients. The study comprised two groups: nontumoral bladder tissue specimens from 20 patients (group I) and tissue specimens from 61 patients with bladder carcinoma (group II). In both groups the tissue specimens were obtained between November 1992 and November 1993, and during the follow-up period until July 1998. p53 expression was determined by a semi-quantitative method based on an immunohistochemical technique (NCL-p53-DO7, Novocastra). CONCLUSIONS: p53 oncoprotein was not found to be useful in the characterization of carcinoma of the urinary bladder.