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PubMed2026

High-dose radiotherapy in patients with high-risk prostate cancers treated with long-term androgen deprivation therapy (GETUG AFU 18): a randomised, phase 3 trial.

BACKGROUND: For patients with high-risk prostate cancer, the role of dose-escalated radiotherapy in combination with long-term androgen deprivation treatment (ADT) is controversial, without any demonstrated benefit on cancer-specific or overall survival. We aimed to evaluate the effect of a 10 Gy dose increase, from 70 Gy to 80 Gy, on progression-free survival in men with high-risk prostate cancer. METHODS: In this multicentre, open-label, randomised, phase 3 trial, we enrolled patients with high-risk prostate cancer, defined as prostate-specific antigen of 20 ng/mL or more, Gleason score of at least 8, or clinical stage T3-T4, from 25 centres in France. Participants were randomly assigned (1:1) by minimisation, stratified by centre and previous pelvic lymph node dissection, to receive prostate-targeted dose-escalated external beam radiotherapy (80 Gy; 2 Gy per fraction for 8 weeks) or standard-dose external beam radiotherapy (70 Gy; 2 Gy per fraction for 7 weeks), combined with long-term ADT. Neither the participants nor the investigators were masked to the allocated treatment. The primary endpoint was 5-year progression-free survival defined as the time from randomisation to first biochemical (defined as prostate-specific antigen >nadir plus 2 ng/mL) or clinical (ie, local, regional, or metastatic) disease progression, analysed in the intention-to-treat population, with 197 events required. 5-year progression-free survival was the prespecified endpoint, and 10-year progression-free survival was additionally reported (post hoc) in view of the low number of events at 5 years. The trial is registered at ClinicalTrials.gov, NCT00967863, and is complete. FINDINGS: Between April 6, 2009, and Jan 24, 2013, 505 patients with high-risk prostate cancer were enrolled; 250 were assigned to receive dose-escalated radiotherapy (80 Gy) and 255 to receive standard dose radiotherapy (70 Gy). All participants were male and ethnicity data were not collected. At a median follow-up of 9&#xb7;5 years (IQR 8&#xb7;5-10&#xb7;3), 5-year progression-free survival was 91&#xb7;4% (95% CI 87&#xb7;0-94&#xb7;4) in the dose-escalation group versus 88&#xb7;1% (83&#xb7;2-91&#xb7;6) in the control group, and 10-year progression-free survival was 83&#xb7;6% (77&#xb7;8-88&#xb7;0) versus 72&#xb7;2% (65&#xb7;3-78&#xb7;0; stratified HR 0&#xb7;56, 95% CI 0&#xb7;40-0&#xb7;78, p<0&#xb7;0001). Grade 3 or worse adverse events assessed at 6 months (acute toxicity) were observed in 60 (24%) of patients in the dose-escalation group and 62 (25%) in the control group. The most frequent grade 3 or worse adverse events were sexual disorders (28 [11%] in the dose-escalation group vs 20 [8%] in the control group) and bladder or urethra disorders (12 [5%] vs 19 [8%]). Adverse events assessed at 5 years (late toxicity) occurred in 118 (70%) of 168 in the dose-escalation group and 122 (73%) of 168 in the control group; grade 3 or worse late toxicities occurred in 19 (8%) participants in the dose-escalated radiotherapy group versus 17 (7%) participants in the control group. The most common late grade 3 adverse event was bladder or urethra disorders (seven [4%] vs three [2%], respectively). Serious adverse events occurred in nine (4%) patients in the dose escalation group and nine (4%) in the control group; none were considered to be treatment related. There were no treatment-related deaths. INTERPRETATION: For patients with high-risk prostate cancer, radiotherapy at a total dose of 80 Gy, in combination with long-term ADT, improved progression-free survival and could be a potential option in this situation. However, given the low number of events, further research is needed to consolidate and confirm the benefit in dose-escalation in prostate cancer-specific survival and overall survival. FUNDING: French National Cancer Institute and AstraZeneca.

Aged↗
PubMed2006

Diffuse high-grade gliomas as second malignant neoplasms after radio-chemotherapy for pediatric malignancies.

OBJECTS: Diffuse high-grade gliomas are known to develop in children after cranial irradiation for other malignancies. Here, clinicopathological characteristics are outlined. METHODS: Nine children received cranial irradiation and chemotherapy for medulloblastoma (n=2) or acute lymphoblastic leukemia (n=7). They developed a high-grade glioma 7-14 years thereafter. Clinical charts, radiologic findings, and pathologic specimens were reviewed. Archival material was stained immunohistochemically. CONCLUSION: Gliomas evolving as second malignant neoplasms show peculiarities and differ in some aspects from their "spontaneous" counterparts. Most are supratentorial, contrast-enhancing, space-occupying lesions. They are composed mainly of small undifferentiated cells, which are mainly negative for glial fibrillary acidic protein and positive for microtubule associated proteins 2 (MAP2). Epidermal growth factor receptor labeling could not be detected in any of them. Ki67-labeling was usually high, whereas p53- and h-ras p21-staining was variable. The median survival was only 12 months despite intensive treatment.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Diagnosis of soft tissue tumors by fine-needle aspiration with combined cytopathology and ancillary techniques.

The diagnosis of mesenchymal neoplasm by fine-needle aspiration biopsy (FNAB) has presented a diagnostic challenge. Most reports claim an accuracy approaching 95%, but while they distinguish benign and malignant lesions, the most problematic group, the intermediary malignant group, is omitted. The purpose of this study was to determine whether rapid cytologic diagnosis of soft-tissue tumors could guide surgeons in therapeutic decisions without the need for a tissue biopsy. Ninety-four FNA cytologic specimens were examined by the National Soft Tissue Consortium of Hungary and compared with the corresponding histology. Ordinary lipomas were excluded. Morphologic evaluation was supplemented by ancillary techniques such as fluorescence in situ hybridization (FISH), DNA cytometry, and immunocytochemistry. From a practical clinicopathological point of view, the cases were grouped in the following categories: 1) tumors with definitive diagnosis: a) high-grade malignant neoplasms (high-grade sarcomas, metastatic carcinomas, lymphoma), b) tumors with precise histogenetic origin by cytogenetics, c) benign tumors; 2) tumors of questionable nature. In the first group there were 74 tumors: 22 high-grade sarcomas, six metastatic carcinomas, one malignant lymphoma, 16 malignant tumors in which the precise histogenetic origin could be established by cytogenetic studies, and 29 benign soft-tissue tumors other than lipomas. In the second group there were 20 tumors comprising benign and malignant soft tissue tumors of low grade, wherein the precise nature of the neoplasm could not be established with confidence on cytologic study, even using ancillary techniques. FNAB of soft-tissue tumors combined with ancillary techniques should be considered a viable diagnostic technique for therapeutic protocols. Although the second group is fairly large, we have reliable, well-characterized categories which provide great freedom for preoperative and surgical treatment, thus providing the best chance for healing.

Adolescent↗
PubMed1993

High-grade transformation of chronic lymphocytic leukemia and low-grade non-Hodgkin's lymphoma. Genotypic confirmation of clonal identity.

The abrupt appearance of a high-grade tumor in patients with low-grade malignant lymphoma usually is associated with an accelerated clinical disease course. The high-grade lymphoma may take a variety of histologic forms and often, but not always, represents evolution of the original low-grade disease, as shown by immunophenotypic or immunogenotypic studies. The authors describe the transformation of a variety of low-grade B-cell neoplasms to high-grade tumors in four patients. The initial diagnoses included chronic lymphocytic leukemia and mantle cell lymphoma in one patient each and low-grade follicular lymphoma in two patients. The high-grade tumors were classified as lymphoblastic lymphoma in one patient and small noncleaved cell lymphoma in two patients. The high-grade component manifests primarily in the peripheral blood as circulating blast-like cells consistent with large-cell lymphoma in the remaining patient. In each case, immunophenotypic studies showed identical monoclonal surface immunoglobulin expression on the low- and high-grade tumors. Immunoglobulin heavy chain gene and kappa light chain gene studies showed identical clonally rearranged bands in paired samples from three of the four patients, a finding indicative of clonal identity. Unexpectedly, dissimilar immunoglobulin light and heavy chain gene rearrangements were detected in the paired samples from one patient with previously diagnosed follicular lymphoma, making the relationship of the two tumors from this patient uncertain; however, additional Southern blot analysis of the bcl-2 gene showed identical rearrangements in both lesions. Furthermore, polymerase chain reaction across the t(14;18) major breakpoint region in both tumors amplified nucleotide fragments of identical size, confirming the clonal identity of the low- and high-grade lymphomas despite the divergent immunoglobulin gene studies. These studies show that low-grade malignant lymphomas of small lymphocytic, mantle cell, or follicular small cleaved cell types may assume high-grade morphologic characteristics, that this change is the result of transformation of the preexisting low-grade malignant neoplasm, and that this progression, like typical Richter's syndrome, is associated with a dramatically accelerated clinical course. In addition, these studies confirm previous reports that disparate immunoglobulin light and heavy chain gene rearrangements are not necessarily an indicator of different cellular origins, and additional genotypic studies occasionally may be required to show the clonal identity of the cell population involved in these morphologic transformations.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed2001

High detection rate of breast ductal carcinoma in situ calcifications on mammographically directed high-resolution sonography.

OBJECTIVE: To assess the high-frequency sonographic characteristics of ductal carcinoma in situ of the breast. METHODS: In a retrospective review, we identified 18 patients with biopsy-proven pure ductal carcinoma in situ who had received mammographic and high-frequency sonographic examinations at transducer frequencies of 8-15 MHz, 8-5 MHz and 5 to 13 MHz [corrected]. RESULTS: All 18 patients had mammographically identified calcifications. Four (22%) of the 18 had either asymmetric focal mammographically identified densities or masses with the calcifications. These calcifications were identified sonographically in 17 (94%) of the 18 patients. In 9 (50%) of 18 patients, the calcifications were associated with sonographically detected malignant masses, and in 3 (17%) of 18 patients the calcifications were within focally dilated ducts. Lesions that had masses or dilated ducts visible on sonography represented 9 (82%) of 11 of the grade 3 neoplasms and only 2 (28%) of 7 of the grade 1 and 2 tumors. This difference was statistically significant (P < .039). CONCLUSIONS: Our study showed that ductal carcinoma in situ may appear on sonography as calcifications, masses, or focally dilated ducts. Those lesions that were associated with masses or dilated ducts on sonography were more likely high-grade histologic specimens.

Breast Neoplasms↗
PubMed1993

Stage I renal cell carcinoma. A clinicopathologic study of 82 cases.

Stage has been established as the most important predictor of prognosis in renal cell carcinoma. The predictive value of other morphologic features is less well established. Therefore, in this study we assessed morphologic parameters in 82 Robson stage I renal cell carcinomas. Insufficient numbers of T1 lesions were present in this series to permit a confident comparison of Robson staging with the Union Internationale Contre le Cancer-American Joint Committee on Cancer TNM (tumor, node, metastasis) staging. Morphologic parameters--including size, character of cytoplasm, nuclear grade, and pelvic invasion--were studied. Both univariate survival analysis and multivariate or tree-structured survival analysis (TSSA) were employed, with disease-free survival and actuarial survival as end points. Nuclear grade was the most important predictor of prognosis in stage I neoplasms by TSSA. Nuclear grade greater than 2 correlated with significantly shorter survival (p = 0.018). Stage I tumors measuring less than 5.0 cm by survival analysis (or 6.0 cm by TSSA) were associated with improved disease-free survival (p = 0.040), although TSSA indicated that the effect was pronounced only in low-grade neoplasms. The character of cell cytoplasm was not independent of nuclear grade (Kruskal-Wallis test, p = 0.028). The contingency table indicated disproportionate numbers of grade 4 mixed cell tumors, grade 3 granular cell tumors, and low-grade clear cell tumors. By TSSA, younger patients with low-grade but larger tumors had a poor clinical outcome. Elderly patients with high-grade tumors had the worst overall survival. None of the other clinical parameters or architectural pattern correlated with survival or disease-free survival. When nuclear grade was combined with tumor size and age at diagnosis in a decision tree, patients with stage I neoplasms were separated into favorable, intermediate, and poor prognosis groups.

Adult↗
PubMed2000

Bilateral breast MALT lymphoma: a case report and review of the literature.

Breast lymphoma is a rare disease. Both primary and secondary breast involvement have been reported. Most primary breast lymphomas are high-grade malignant neoplasms, mainly large cell and Burkitt type. Low-grade lymphomas of the breast, particularly mucosa-associated lymphoid tissue (MALT) lymphomas, have been exceedingly rare. In this report we present a patient with bilateral breast involvement by MALT lymphoma. Our patient developed localized MALT lymphoma in both breasts in a sequential fashion. She was treated with bilateral lumpectomy, followed by radiation therapy to both breasts. The patient is alive and well more than 1 year after therapy with no recurrence. We believe this is the first such case described in detail in the literature.

Aged↗
PubMed2001

Comparative studies of the estrogen receptors beta and alpha and the androgen receptor in normal human prostate glands, dysplasia, and in primary and metastatic carcinoma.

An antibody, GC-17, thoroughly characterized for its specificity for estrogen receptor-beta (ER-beta), was used to immunolocalize the receptor in histologically normal prostate, prostatic intraepithelial neoplasia, primary carcinomas, and in metastases to lymph nodes and bone. Comparisons were made between ER-beta, estrogen receptor-alpha (ER-alpha), and androgen receptor (AR) immunostaining in these tissues. Concurrently, transcript expression of the three steroid hormone receptors was studied by reverse transcriptase-polymerase chain reaction analysis on laser capture-microdissected samples of normal prostatic acini, dysplasias, and carcinomas. In Western blot analyses, GC-17 selectively identified a 63-kd protein expressed in normal and malignant prostatic epithelial cells as well as in normal testicular and prostatic tissues. This protein likely represents a posttranslationally modified form of the long-form ER-beta, which has a predicted size of 59 kd based on polypeptide length. In normal prostate, ER-beta immunostaining was predominately localized in the nuclei of basal cells and to a lesser extent stromal cells. ER-alpha staining was only present in stromal cell nuclei. AR immunostaining was variable in basal cells but strongly expressed in nuclei of secretory and stromal cells. Overall, prostatic carcinogenesis was characterized by a loss of ER-beta expression at the protein and transcript levels in high-grade dysplasias, its reappearance in grade 3 cancers, and its diminution/absence in grade 4/5 neoplasms. In contrast, AR was strongly expressed in all grades of dysplasia and carcinoma. Because ER-beta is thought to function as an inhibitor of prostatic growth, androgen action, presumably mediated by functional AR and unopposed by the beta receptor, may have provided a strong stimulus for aberrant cell growth. With the exception of a small subset of dysplasias in the central zone and a few carcinomas, ER-alpha-stained cells were not found in these lesions. The majority of bone and lymph node metastases contained cells that were immunostained for ER-beta. Expression of ER-beta in metastases may have been influenced by the local microenvironment in these tissues. In contrast, ER-alpha-stained cells were absent in bone metastases and rare in lymph nodes metastases. Irrespective of the site, AR-positive cells were found in all metastases. Based on our recent finding of anti-estrogen/ER-beta-mediated growth inhibition of prostate cancer cells in vitro, the presence of ER-beta in metastatic cells may have important implications for the treatment of late-stage disease.

Aged↗
PubMed2004

INK4a-ARF alterations in Barrett's epithelium, intraepithelial neoplasia and Barrett's adenocarcinoma.

INTRODUCTION: The INK4a-ARF [CDKN2A]- locus on chromosome 9p21 encodes for two tumour suppressor proteins, p16INK4a and p14ARF, which act as upstream regulators of the Rb-CDK4 and p53 pathways. To study the contribution of each pathway to the carcinogenesis of Barrett's adenocarcinoma, we analysed the alterations of p14ARF and p16INK4a in preneoplastic and neoplastic lesions of this disease. MATERIALS AND METHODS: After microdissection, DNA of 15 Barrett's adenocarcinomas, 40 Barrett's intraepithelial neoplasms (n=20 low- and n=20 high-grade) and 15 Barrett's mucosa without neoplasia was analysed for INK4-ARF inactivation using DNA sequence and loss of heterozygosity (LOH) analysis, methylation-specific polymerase chain reaction, restriction-enzyme-related polymerase chain reaction and immunohistochemistry. RESULTS: We detected 9p21 LOH, p16INK4a methylation and p16INK4a mutations in Barrett's adenocarcinomas in 5 of 15 (33%), 8 of 15 (53%) and 1 of 15 (7%) patients, respectively. P14ARF was methylated in 3 of 15 (20%) adenocarcinomas. In Barrett's intraepithelial neoplasia, p16INK4a was altered in 12 of 20 (60%) high-grade and in 4 of 20 (20%) low-grade intraepithelial neoplasms. In Barrett's mucosa without intraepithelial neoplasia p16(INK4a) was methylated in one case (7%). P14ARF was intact in Barrett's mucosa without intraepithelial neoplasia. CONCLUSIONS: We conclude that most Barrett's intraepithelial neoplasms contain genetic and/or epigenetic INK4a-ARF alterations. Methylation of p16INK4a appears to be the most frequent epigenetic defect in the neoplastic progression of Barrett's tumourigenesis.

Barrett Esophagus↗
PubMedDate not supplied

Ovarian neoplasms and pregnancy.

The aim of our study was to investigate the incidence of ovarian malignant neoplasms in pregnancy. In the prospective study, during a 2-year period of time, we had the ethical dilemma concerning the conciliar treatment vs the patient's wish to deliver and save the reproductive capabilities. We examined 37 pregnant women; the incidence of ovarian cancer was 13.5% vs 6.5% in other works. Diagnoses were made by ultrasound criteria and physical examinations. Statistically significant results were obtained by Student t test. Mean gestational age was 20.1 weeks and mean age 31.1 years. Treatment depends on the neoplasms type, grade, and presence of the metastatic pathways. In benign neoplasms, we used laparoscopic treatment with minor invasion. Distribution of benign neoplasms was in the same range as that in other works.

Adult↗
PubMed1993

Computed tomography and histologic limits in glial neoplasms: tumor types and selection for volumetric resection.

Selective and accurate resection of any computed tomography (CT) or magnetic resonance imaging (MRI) defined intracranial volume is possible by employing imaging-based computer-assisted volumetric stereotactic methods. Although the target volume can be any intracranial lesion, volumetric resection techniques were most frequently applied to the most commonly referred intraaxial lesions: glial neoplasms located in eloquent brain regions. Requirements for understanding of glial neoplasms as target volumes prompted investigations of the three-dimensional spatial configuration of these lesions, their histologic margins, and the accuracy with which these margins could be detected on CT and MRI. Stereotactic serial biopsy studies have shown that glial neoplasms frequently comprise two elements: tumor tissue and isolated tumor cells which infiltrate brain parenchyma. The tumor tissue component of high grade gliomas is most accurately defined by the volume which exhibits contrast enhancement. However, tumor tissue in low grade (nonpilocytic) gliomas is usually indistinguishable from infiltrated parenchyma on CT and MRI; both are hypodense on CT and do not usually exhibit contrast enhancement. Stereotactic serial biopsy is the only reliable method by which CT hypodense tumor tissue can be differentiated from infiltrated parenchyma in low grade (nonpilocytic) astrocytomas, oligodendrogliomas, and mixed gliomas. Stereotactic volumetric resection of infiltrated parenchyma defined by CT/MRI is advisable only in nonessential brain regions. In eloquent brain areas, stereotactic resection is appropriate for the glial tumor tissue component of high grade glial neoplasms, pilocytic astrocytomas, and low grade CT hypodense gliomas in which a stereotactic serial biopsy procedure has confirmed tumor tissue only.

Biopsy↗
PubMed2005

Supratentorial low-grade gliomas. Neuroradiology.

The radiologic modality that most likely provides the imaging information needed in a patient suspected of having a brain tumors is magnetic resonance imaging. A brain tumors can be reliably ruled out, if the standard magnetic resonance examination is performed properly and experts interpret the results as negative for tumor. In this paper we will illustrate morphological aspects of low-grade supratentorial neoplasms, including tumors of neuroepithelial tissue, such as low-grade diffuse fibrillary astrocytomas, and circumscribed astrocytic lesions (pilocytic astrocytoma, pleomorphic xantoastrocytoma and subependymal giant cell astrocytoma). Then the main practical applications of functional imaging in neurosurgery will be also debated.

Brain↗
PubMed1996

Solid and papillary epithelial neoplasm of the pancreas: CT and MR findings.

Solid and papillary epithelial neoplasm of the pancreas is a very rare low-grade malignant neoplasm with only 126 cases reported in the literature and seen mostly in young female patients. Surgical excision means cure in cases before malignant degeneration developed. Its characteristic findings are typical location in the tail of the pancreas, peripheral capsule formation, hypodensity on CT images, and hyperintense internal signal characteristics on T1-weighted MR images secondary to hemorrhage and accumulation of methemoglobine molecule. These findings are enough for the preoperative diagnosis that may lead to early surgery and cure. We present the CT and MR findings of this very rare neoplasm in a case report.

Adult↗
PubMed1998

Intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) exhibits CD5 immunoreactivity: new evidence for thymic differentiation.

AIMS: Cases of intrathyroidal epithelial thymoma (ITET)/carcinoma showing thymus-like differentiation (CASTLE) were examined for CD5 immunoreactivity, a feature of true thymic carcinoma, but not other thymic epithelial neoplasms or carcinomas of other sites. ITET/CASTLE, a rare, low-grade malignant neoplasm arising within the thyroid gland which resembles lymphoepithelioma-like and squamous cell carcinoma of the thymus, is postulated to arise from remnants of branchial pouch capable of thymic differentiation, but thymic differentiation in this neoplasm remains unproven. METHODS AND RESULTS: The largest published series of cases of ITET/CASTLE was examined for CD5 immunoreactivity using an anti-CD5 antibody reactive in fixed, paraffin-embedded tissue with microwave antigen retrieval. Neoplastic cells in all five cases of ITET/CASTLE studied were immunoreactive for CD5, including foci of tumour metastatic to lymph node and lung. In contrast, none of five cases of thyroid carcinoma with squamous differentiation was immunoreactive for CD5. A minority of cases of typical thyroid carcinomas showed some weak immunoreactivity for CD5. Other carcinomas of the head and neck were nonimmunoreactive for CD5. CONCLUSIONS: CD5 immunoreactivity in ITET/CASTLE is new evidence in support of thymic differentiation in this neoplasm.

Adult↗