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Paola Collini

Publications and source records attributed to Paola Collini.

At least 37 records · Page 2Linked to original sources
PubMed2005

Evolving treatment strategies for parameningeal rhabdomyosarcoma: the experience of the Istituto Nazionale Tumori of Milan.

BACKGROUND: Ninety pediatric patients with parameningeal rhabdomyosarcoma (PM-RMS) were treated between 1970 and 2002 at the Istituto Nazionale Tumori, Milan. METHODS: Combined treatment was implemented in high-risk patients with whole-brain irradiation and intrathecal chemotherapy between 1978 and 1981 and intrathecal methotrexate alone between 1982 and 1987. Radiotherapy was given with conventional fractionation until 1988 and hyperfractionated accelerated radiotherapy (HART) thereafter. RESULTS: The 5-year disease-free survival was 41.3%, increasing from 15.4% (1970-1977) to 55.9% (1989-2002) for localized cases. Local failure rates were 41% and 24% with conventional fractionation and HART, respectively. In patients treated with HART, acute toxicities were more pronounced, but the treatment compliance was better. Severe radiation-related late sequelae were observed. CONCLUSIONS: The outcome for patients with PM-RMS has improved over the years but is still not as satisfactory as that for patients with RMS of other sites. Thanks to improvements in radiotherapy techniques and chemotherapy efficacy, meningeal prophylaxis is no longer necessary. Although more evidence is needed to confirm our data, the results obtained with twice-daily HART seem promising.

Adolescent↗
PubMed2005

WT1 gene analysis in sporadic early-onset and bilateral wilms tumor patients without associated abnormalities.

The WT1 gene is responsible for two different genetic conditions characterized by genitourinary anomalies and susceptibility to Wilms tumor (WT): the WAGR syndrome and the Denys-Drash syndrome. Although only rarely, WT1 constitutional mutations have been reported also in WT patients without congenital defects. Due to the high survival rates that characterize the disease, these individuals must be identified and counseled in relation to their risk to transmit a cancer-predisposing genetic lesion to their offspring. Recently, tumor bilaterality and early age of onset have been suggested to be risk factors for carrying germline WT1 mutations. The authors investigated 20 patients with sporadic WT, without evidence of congenital abnormalities, diagnosed before 2 years of age and/or with bilateral presentation, for the occurrence of WT1 mutations. Southern blot analyses identified homozygous whole-gene or intragenic deletions at the tumor level in three cases. However, none of the identified alterations was found to be present at the germline level. In addition, no mutation in the coding exons and flanking sequences of WT1 was detected in the remaining 17 cases. These results suggest that early age of diagnosis and bilaterality are not by themselves efficient predictors of germline WT1 alterations in WT patients without associated abnormalities.

Age of Onset↗
PubMed2005

Wilms tumor in monozygous twins: clinical, pathological, cytogenetic and molecular case report.

The concomitant occurrence of Wilms tumor (WT) was observed in two monozygotic twin sisters without evidence of congenital malformations. Twin 1 was diagnosed with a stage I WT at 11 months of age, whereas twin 2 developed a bilateral (stage V) WT at 13 months of age. In both cases pathologic examination showed a nonanaplastic stromal type WT, with marked rhabdomyomatous elements. Cytogenetic analyses performed on blood samples and on tumor specimens revealed no karyotypic abnormality. No alteration of the WT1 and POU6F2 genes was identified in constitutional and tumor DNA of both sisters, and no anomaly in WT1 expression was evidenced in the normal kidney of one of them. However, loss of heterozygosity on chromosome 11p, involving the alleles of maternal origin, was detected both in the single tumor of twin 1 and in the two distinct tumors of twin 2, thus suggesting a common etiology of the diseases. To the authors' knowledge, this is the first report describing at both the clinical and genetic level a couple of monozygotic twins concordant for WT development.

Child, Preschool↗
PubMed2005

Sequential chemotherapy, high-dose thiotepa, circulating progenitor cell rescue, and radiotherapy for childhood high-grade glioma.

Childhood malignant gliomas are rare, but their clinical behavior is almost as aggressive as in adults, with resistance to therapy, rapid progression, and not uncommonly, dissemination. Our study protocol incorporated sequential chemotherapy and high-dose thiotepa in the preradiant phase, followed by focal radiotherapy and maintenance with vincristine and lomustine for a total duration of one year. The induction treatment consisted of two courses of cisplatin (30 mg/m2) plus etoposide (150 mg/m2) x 3 days and of vincristine (1.4 mg/m2) plus cyclophosphamide (1.5 g/m2) plus high-dose methotrexate (8 g/m2), followed by high-dose thiotepa (300 mg/m2 x 3 doses), with harvesting of peripheral blood progenitor cells after the first cisplatin/etoposide course. From August 1996 to March 2003, 21 children, 14 females and 7 males, with a median age of 10 years were enrolled, 18 presenting with residual disease after surgery. Histologies were glioblastoma multiforme in 10, anaplastic astrocytoma in nine, and anaplastic oligodendroglioma in two; sites of origin were supratentorial areas in 17, spine in two, and posterior fossa in two. Of the 21 patients, 12 have died (10 after relapse, with a median time to progression for the whole series of 14 months; one with intratumoral bleeding at 40 months after diagnosis; and one affected by Turcot syndrome for duodenal cancer relapse). Four of 12 relapsed children had tumor dissemination. At a median follow-up of 57 months, overall survival and progression-free survival at four years were 43% and 46%, respectively. Sequential and high-dose chemotherapy can be afforded in front-line therapy of childhood malignant glioma without excessive morbidity and rather encouraging results.

Adolescent↗
PubMed2005

Does melanoma behave differently in younger children than in adults? A retrospective study of 33 cases of childhood melanoma from a single institution.

OBJECTIVE: To ascertain whether childhood melanoma presents any peculiar clinical features or differences in prognosis with respect to adults, we retrospectively analyzed the data from 33 patients who were up to 14 years of age and treated for cutaneous melanoma at the Istituto Nazionale Tumori, Milan, over a 25-year period. METHODS: Primary lesions were amelanotic in half of the cases and raised in 73%. Lower extremities were the most common primary sites. Histologically, 9 cases were classified as nodular type, and median thickness was 2.5 mm. Nine children had nodal involvement at diagnosis, 2 in-transit metastases, and 1 distant spread. Surgery was the mainstay of treatment; 9 patients underwent lymph node dissection, 3 received chemotherapy, and 2 received radiotherapy. RESULTS: With a median follow-up of 122 months, 5-year event-free survival and overall survival were 60% and 70%, respectively. Age seemed to correlate with survival, event-free survival being 90% in children under 10 and 47% in older patients, although the initial microstaging seemed worse in the former. CONCLUSION: By comparison with adult cases, childhood melanoma can have a higher percentage of atypical clinical features (amelanotic and raised lesions), nodular histotype, and thick lesions. Although we have no data to support any suggestion of biological differences between young children and adolescents or adults, our findings give the impression that melanoma behaves differently in the younger age group.

Adolescent↗
PubMed2004

Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer.

Papillary thyroid carcinoma (PTC) is associated with RET and NTRK1 rearrangements and BRAF mutations. A series of 60 PTCs collected in a single center from Italian patients were histologically re-examined and subclassified as well differentiated or tall cell variant. The sample collection was analysed for the presence of all the reported PTC-associated genetic alterations through DNA or cDNA amplification, followed by automated sequencing. The analysis of exons 11 and 15 of BRAF gene revealed the T1796A (V599E) mutation in 32% of cases, and this alteration is significantly associated with PTC tall cell variant. Oncogenic rearrangements of RET and NTRK1 receptors were found in 33 and 5% of cases, respectively. No Ras mutations were detected. Overall, genetic alterations were detected in two-thirds of samples, and in no single case more than one mutational event was found simultaneously. Gene expression profiling of a subset of 31 tumors performed using cDNA microarray chips showed no strong differences in global gene expression among the different cases. However, a supervised analysis of the obtained data identified a subset of genes differentially expressed in tumors carrying BRAF mutation or RTK rearrangement.

Adenocarcinoma, Papillary↗
PubMed2004

Synovial sarcoma: a retrospective analysis of 271 patients of all ages treated at a single institution.

BACKGROUND: The optimal treatment strategy for synovial sarcoma (SS) is subject to debate, and different strategies have been used for pediatric and adult patients. The current retrospective analysis examined a large group of patients of all ages who were treated at a single institution over a 30-year period. METHODS: The study included 271 patients who ranged in age from 5 years to 87 years; 255 had localized disease, which was macroscopically resected in 215 cases and deemed unresectable at diagnosis in 40 cases. Chemotherapy was administered to 41% of patients, corresponding to 76% of patients age or 16 years and < 20% of older patients; 28% of patients with macroscopically resected disease received chemotherapy on an adjuvant basis. RESULTS: The 5-year event-free survival rate for the study cohort as a whole was 37%, although this rate varied with age (66%, 40%, and 31% for patients age < or = 16 years, 17-30 years, and > 30 years, respectively). Chemotherapy was used more commonly for children than for adults. Among patients with surgically resected disease, the 5-year metastasis-free survival (MFS) rate was 60% for those who were treated with chemotherapy and 48% for those who were not; the benefit associated with chemotherapy use appeared to be greatest for patients age > or = 17 years who had tumors measuring > 5 cm (MFS, 47% [chemotherapy] vs. 27% [no chemotherapy]). In the subgroup of patients with measurable disease, the rate of tumor response to chemotherapy was approximately 48%. CONCLUSIONS: Although the authors await more convincing proof of the efficacy of adjuvant chemotherapy in the treatment of adult soft tissue sarcoma, they recommend that patients with high-risk SS (tumor size > 5 cm) be the first to be considered for this type of treatment.

Adolescent↗
PubMed2004

Adult Wilms' tumor: A monoinstitutional experience and a review of the literature.

BACKGROUND: The authors reviewed their institutional experience regarding adult patients with Wilms' tumor (WT) to assess their clinical characteristics and compliance with respect to children's treatment guidelines. METHODS: A total of 17 adult patients (median age at the time of diagnosis of 17.5 years; range, 16-29 years) were referred to the study institute between 1983 and 2001 and were followed for a median of 131 months. The treatment modality was planned according to the two consecutive Italian protocols for WT that were active during the referral years. The patients were staged according to the National Wilms Tumor Study-4 (NWTS) staging system as follows: eight patients had Stage II disease, four patients had Stage III disease, and five patients had Stage IV disease. RESULTS: All the patients but one underwent nephrectomy, with three incomplete surgeries performed. Two patients with Stage II disease were treated elsewhere with nephrectomy only and they were admitted to the study institution at the time of disease recurrence. Anaplasia was found to be present in only one patient with Stage IV disease. The authors noted 9 cases of disease recurrence or progression occurring during treatment and 6 of these 9 patients died of their disease, with an overall survival rate of 62.4% at 5 years. CONCLUSIONS: Compared with children, adults with WT are reported to have a worse prognosis. In the current study, the authors found that poor compliance with specific therapeutic guidelines may contribute to this poorer outcome. Because of the rarity of this disease, adults with WT are at a risk of either undertreatment or incorrect treatment.

Adolescent↗
PubMed2004

Hyperfractionated radiotherapy and chemotherapy for childhood ependymoma: final results of the first prospective AIEOP (Associazione Italiana di Ematologia-Oncologia Pediatrica) study.

PURPOSE: A postsurgical "stage-based" protocol for ependymoma was designed. METHODS AND MATERIALS: Children were given: (1) focal hyperfractionated radiotherapy (HFRT) if with no evidence of disease (NED), or (2) 4 courses with VEC followed by HFRT for residual disease (ED). HFRT dose was 70.4 Gy (1.1 Gy/fraction b.i.d.); VEC consisted of VCR 1.5 mg/m2 1/w, VP16 100 mg/m2/day x 3, CTX 3 g/m2 d 1. When feasible, second-look surgery was recommended. RESULTS: Sixty-three consecutive children were enrolled: 46 NED, 17 ED; the tumor was infratentorial in 47 and supratentorial in 16, with spinal metastasis in 1. Of NED patients, 35 of 46 have been treated with HFRT; 8 received conventionally fractionated radiotherapy, and 3 received no treatment. Of the 17 ED patients, 9 received VEC + HFRT; violations due to postsurgical morbidity were as follows: HFRT only (2), conventionally fractionated radiotherapy (3) + VEC (2), and no therapy (1). Objective responses to VEC were seen in 54%; objective responses to RT were seen in 75%. Overall survival and progression-free survival at 5 years for all 63 children were 75% and 56%, respectively; for the NED subgroup, 82% and 65%; and for the ED subgroup, 61% and 35%, respectively. All histologies were centrally reviewed. At multivariate analysis, grading, age, and site proved significant for prognosis. CONCLUSIONS: HFRT, despite the high total dose adopted, did not change the prognosis of childhood ependymoma as compared to historical series: New radiotherapeutic approaches are needed to improve local control. Future ependymoma strategies should consider grading when stratifying treatment indications.

Adolescent↗
PubMed2004

Germline mutations of the POU6F2 gene in Wilms tumors with loss of heterozygosity on chromosome 7p14.

Wilms tumor (WT) is a kidney malignancy of childhood characterized by highly heterogeneous genetic alterations. We previously reported the molecular and cytogenetic characterization of a WT (Case 30) carrying an interstitial deletion in chromosome 7p14 between markers D7S555 and D7S668. Loss of heterozygosity (LOH) analyses had revealed that this same region was lost in 8 out of 38 examined WTs, suggesting that the identified interval contains a putative tumor suppressor gene. To confirm this hypothesis, in this work, we analyzed an additional 35 WTs, four of which showed LOH in the region of interest. Furthermore, we were able to more accurately define the extension of the deletion in Case 30, mapping it within an interval not exceeding 390 kb, proximally to D7S555. To date, only a single expressed gene, POU6F2 (the POU domain, class 6, transcription factor 2; also known as RPF1), has been recognized in this interval. Sequencing of the gene in the 12 WTs showing LOH and in a corresponding numbers of WT cases without LOH, led to the identification of two germline nucleotide substitutions. The first occurred in the 5'-untranslated region, while the second caused an amino acid change in a glutamine repeat domain. These mutations, whose occurrence was not observed in more than 100 control subjects, were detected in two patients showing the loss of the constitutionally wild-type allele in tumor DNA. Together with the finding of the expression of the POU6F2 mouse homolog in both fetal and adult kidney, our observations suggest that the gene is a tumor suppressor and is involved in hereditary predisposition to WT.

Alleles↗
PubMed2004

Molecular detection of dopamine decarboxylase expression by means of reverse transcriptase and polymerase chain reaction in bone marrow and peripheral blood: utility as a tumor marker for neuroblastoma.

A highly sensitive molecular method was used to evaluate the presence of dopamine decarboxylase (DDC) mRNA in the bone marrow and peripheral blood of patients with neuroblastoma (NB). DDC, like tyrosine hydroxylase (TH), is an enzyme involved in the catecholamine synthesis pathway and has recently been proposed as a specific marker of NB among pediatric malignancies. DDC transcript was detected in five of five NB cell lines, 10 of 10 NB primary tumors, 17 of 18 (94%) bone marrow samples, and 12 of 18 (66%) blood samples drawn at diagnosis in 18 patients affected by disseminated NB. In contrast, no PCR signal was found in 20 bone marrow samples obtained from patients with other malignancies or in eight of nine marrow and blood samples drawn from patients with localized NB (two stage 2 and seven stage 3). In addition, all marrow and blood samples obtained from NB patients at relapse revealed DDC mRNA. Furthermore, the percentage of DDC-positive samples was lower among the samples drawn from these patients during treatment. By comparison with conventional methods for disease evaluation, DDC transcript research can increase the sensitivity of NB cell detection in marrow and blood samples at diagnosis and during the treatment and follow-up of NB patients. These results suggest that finding DDC mRNA in NB patients could be a potential marker for minimal residual disease study.

Biomarkers, Tumor↗
PubMed2003

Antigen-specific immunity in neuroblastoma patients: antibody and T-cell recognition of NY-ESO-1 tumor antigen.

Neuroblastoma cells have been shown to express molecularly defined tumor-associated antigens, which could represent potential targets of T and/or B cell-mediated immunity. However, the existence of a spontaneous immune response to such tumor antigens in neuroblastoma patients has yet to be investigated. In the present work we addressed the issue of whether NY-ESO-1, a germ cell antigen aberrantly expressed in different tumor types, is expressed by neuroblastoma cells and may represent a target for humoral and/or cellular immune responses in neuroblastoma patients. We found that a large fraction of neuroblastoma biopsies, independently from the clinical stage and degree of tumor cell differentiation, expressed significant levels of NY-ESO-1 as assessed by reverse transcription-PCR and immunohistochemistry. NY-ESO-1-specific IgG antibodies were detected in the sera of 10% of neuroblastoma patients with stage III or IV disease, but not in patients in clinical remission or with earlier stages. This suggests that antibody production occurred as a late event in the course of disease. NY-ESO-1-specific immune responses were observed for CD4(+) and CD8(+) T cells from peripheral blood lymphocytes in 4 of 8 neuroblastoma patients, as detected by IFN-gamma enzyme-linked immunospot assay after in vitro stimulation either with the NY-ESO-1 recombinant protein or with the HLA-A2-restricted peptide NY-ESO-1(157-167). NY-ESO-1-specific CD4(+) and CD8(+) T cells were also able to recognize NY-ESO-1 expressing neuroblastoma cells. The presence of T cells specific for NY-ESO-1 antigen was not associated with the stage of disease, or to the presence or absence of NY-ESO-1 specific antibodies. We conclude that NY-ESO-1 is an immunogenic antigen in neuroblastoma patients and represents a candidate target for immune-based therapy.

Antigens, Neoplasm↗
PubMed2003

Rhabdomyosarcoma in adults. A retrospective analysis of 171 patients treated at a single institution.

BACKGROUND: The goal of the current study was to clarify treatment outcomes for adult patients with rhabdomyosarcoma (RMS). Published series have reported definitively worse results for adults with RMS compared with children with RMS. This finding casts doubt on whether RMS is the same disease in adults as it is in children. METHODS: Of 190 patients with RMS who were age 18 years or older and whose cases were recorded over a 25-year span in the pathology database of the Istituto Nazionale Tumori (Milan, Italy), 171 could be analyzed retrospectively for treatment outcome. The authors attempted to stratify patients according to the degree to which they had been treated appropriately, based on current treatment guidelines for childhood RMS. RESULTS: The overall rate of response to chemotherapy was 85%. For the entire series, 5-year event-free survival and 5-year overall survival (OS) were 28% and 40%, respectively. Among the 110 patients with embryonal, alveolar, or 'not otherwise specified' RMS, 5-year OS was 46%; however, 5-year OS was 61% for patients within this group (39% of the total) who had high scores for appropriate treatment. CONCLUSIONS: The current series parallels other published series in that it confirms the finding of a relatively poor long-term outcome for adult patients with RMS. However, for patients whose treatment adhered to the current guidelines for treatment of children, outcome was similar to what has been reported in pediatric series. In addition, the rate of response to chemotherapy for the entire series was similar to the rate typically observed among children. These findings suggest that adults and children with RMS should receive similar treatment. Treatment protocols adopted from pediatric programs but tailored to adults could increase adults' chances of receiving appropriate treatment; prospective studies are needed to test this idea.

Adult↗
PubMed2003

Differential expression of telomerase activity in neuroendocrine lung tumours: correlation with gene product immunophenotyping.

Telomerase activity was examined by the telomeric repeat amplification protocol (TRAP) assay in 38 neuroendocrine (NE) lung tumours. A significantly (p = 0.001) different frequency of telomerase positivity was observed among different histological tumour types. Specifically, a positive TRAP signal was observed in 14 of 15 (93%) small cell lung cancers (SCLCs), 7 of 8 (87%) large-cell NE carcinomas (LCNECs), and only 1 of 15 (7%) typical carcinoid tumours. When telomerase activity was correlated with the gene product-based immunophenotypic profile of individual tumours, it was found that the absence of telomerase activity was associated with a lack of bcl-2, p53, and c-kit expression, and characterized by a low proliferation index consistent with the absence of cdk-4 expression and the presence of the cdk inhibitor Rb. Such a phenotype was appreciable in most of the carcinoid tumours. Conversely, telomerase-positive tumours generally showed an immunophenotype consistent with gene product alterations (including high expression of bcl-2, p53, and c-kit, and loss of Rb) and were characterized by a high proliferation index. These telomerase data support the previously reported evidence for two genetically unrelated groups of NE lung tumours (SCLC, and to some extent LCNEC, versus carcinoid tumours) that have distinct phenotypic profiles.

Biomarkers, Tumor↗