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1.
Nat Commun ; 12(1): 1797, 2021 Mar 30.
Article in English | MEDLINE | ID: mdl-33785749

ABSTRACT

So far, only two interstellar objects have been observed within our Solar System. While the first one, 1I/'Oumuamua, had asteroidal characteristics, the second one, 2I/Borisov, showed clear evidence of cometary activity. We performed polarimetric observations of comet 2I/Borisov using the European Southern Observatory Very Large Telescope to derive the physical characteristics of its coma dust particles. Here we show that the polarization of 2I/Borisov is higher than what is typically measured for Solar System comets. This feature distinguishes 2I/Borisov from dynamically evolved objects such as Jupiter-family and all short- and long-period comets in our Solar System. The only object with similar polarimetric properties as 2I/Borisov is comet C/1995 O1 (Hale-Bopp), an object that is believed to have approached the Sun only once before its apparition in 1997. Unlike Hale-Bopp and many other comets, though, comet 2I/Borisov shows a polarimetrically homogeneous coma, suggesting that it is an even more pristine object.

2.
Philos Trans A Math Phys Eng Sci ; 375(2097)2017 07 13.
Article in English | MEDLINE | ID: mdl-28554971

ABSTRACT

We present a summary of the campaign of remote observations that supported the European Space Agency's Rosetta mission. Telescopes across the globe (and in space) followed comet 67P/Churyumov-Gerasimenko from before Rosetta's arrival until nearly the end of the mission in September 2016. These provided essential data for mission planning, large-scale context information for the coma and tails beyond the spacecraft and a way to directly compare 67P with other comets. The observations revealed 67P to be a relatively 'well-behaved' comet, typical of Jupiter family comets and with activity patterns that repeat from orbit to orbit. Comparison between this large collection of telescopic observations and the in situ results from Rosetta will allow us to better understand comet coma chemistry and structure. This work is just beginning as the mission ends-in this paper, we present a summary of the ground-based observations and early results, and point to many questions that will be addressed in future studies.This article is part of the themed issue 'Cometary science after Rosetta'.

3.
Nature ; 515(7525): 88-91, 2014 Nov 06.
Article in English | MEDLINE | ID: mdl-25327247

ABSTRACT

Isolated cool white dwarf stars more often have strong magnetic fields than young, hotter white dwarfs, which has been a puzzle because magnetic fields are expected to decay with time but a cool surface suggests that the star is old. In addition, some white dwarfs with strong fields vary in brightness as they rotate, which has been variously attributed to surface brightness inhomogeneities similar to sunspots, chemical inhomogeneities and other magneto-optical effects. Here we describe optical observations of the brightness and magnetic field of the cool white dwarf WD 1953-011 taken over about eight years, and the results of an analysis of its surface temperature and magnetic field distribution. We find that the magnetic field suppresses atmospheric convection, leading to dark spots in the most magnetized areas. We also find that strong fields are sufficient to suppress convection over the entire surface in cool magnetic white dwarfs, which inhibits their cooling evolution relative to weakly magnetic and non-magnetic white dwarfs, making them appear younger than they truly are. This explains the long-standing mystery of why magnetic fields are more common amongst cool white dwarfs, and implies that the currently accepted ages of strongly magnetic white dwarfs are systematically too young.

4.
Science ; 310(5746): 265-9, 2005 Oct 14.
Article in English | MEDLINE | ID: mdl-16150977

ABSTRACT

On 4 July 2005, many observatories around the world and in space observed the collision of Deep Impact with comet 9P/Tempel 1 or its aftermath. This was an unprecedented coordinated observational campaign. These data show that (i) there was new material after impact that was compositionally different from that seen before impact; (ii) the ratio of dust mass to gas mass in the ejecta was much larger than before impact; (iii) the new activity did not last more than a few days, and by 9 July the comet's behavior was indistinguishable from its pre-impact behavior; and (iv) there were interesting transient phenomena that may be correlated with cratering physics.


Subject(s)
Meteoroids , Cosmic Dust , Jupiter , Organic Chemicals , Photometry
5.
Eur J Clin Pharmacol ; 58(8): 495-500, 2002 Nov.
Article in English | MEDLINE | ID: mdl-12451425

ABSTRACT

OBJECTIVE: . The aim of this study was to evaluate the number and the characteristics of medicines approved for children in Europe by the European Agency for the Evaluation of Medicinal Products (EMEA) and whether the paediatric studies supporting the authorisation were in accordance with the Note for Guidance on the Clinical Investigation of Medicinal Products in children (CPMP/ICH/2711/99). We also considered any possible difference between the EMEA and the Food and Drug Administration (FDA) paediatric medicines evaluations. METHODS: . We examined the drugs authorised by the EMEA through the centralised procedure from January 1995 to September 2001 deriving information from the "European Medicines - Database" (EMD) set up in 1998 by the Italian Group for Pharmacoeconomic Studies (GISF) and sponsored by the Italian Ministry of Health. The analysis of paediatric data has been managed by experts belonging to the Clinical Pharmacology Working Group of the Italian Paediatric Society. The following parameters were assessed: active substance, year of approval, anatomical therapeutic and chemical (ATC) code, therapeutic indications, age for which the drug is authorised, interest to children and paediatric studies supporting a paediatric authorisation. European Public Assessment Reports (EPARs) were considered as reference sources. RESULTS: . The median percentage of drugs authorised for children from 1995 to 2001 (September) is 35% of the total of commercially available drugs; only 16 medicines have been approved for children under 2 years of age (11%), ten of these being vaccines. Medicines for children shared out 9 ATC classes, 24 belonging to the J- (anti-infective agents) -ATC class. Thirty-nine medicines were authorised on the basis of at least one clinical trial (27 phase III, 6 phase II, 6 phase I) while eight active substances have been licensed without any paediatric investigation. CONCLUSIONS: . Under the EMEA centralised procedure, several active substances have been licensed for children. Consequently serious and life-threatening diseases as AIDS and diabetes are now treatable, in a legal framework overcoming the orphan status of the past years. Despite the reported encouraging results, the number of drugs devoted to children remain low and important ATC classes, as L-(oncology) or N-(neurology), are still 'orphans' of innovative medicines. At the same time few medicinal products are specifically studied in children. Consequently, more efforts have to be made to increase the number of drugs assessed and licensed for the paediatric population, and manufacturers should be required to supply data on the effects of new drugs in children when the products are expected to offer a benefit over existing therapies.


Subject(s)
Drug Approval/legislation & jurisprudence , Drug Utilization Review , Government Agencies/legislation & jurisprudence , Licensure , Pediatrics , Adolescent , Age Factors , Child , Child, Preschool , Databases, Factual , Drug Approval/organization & administration , Drug Labeling/legislation & jurisprudence , Europe , Humans , Infant , Infant, Newborn , Orphan Drug Production/legislation & jurisprudence , United States , United States Food and Drug Administration
6.
Bone Marrow Transplant ; 28(2): 131-6, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11509930

ABSTRACT

This retrospective study from the Italian Association of Pediatric Hematology Oncology-Bone Marrow Transplant Group (AIEOP-TMO) reports the results of consolidation with high-dose melphalan and autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with acute myeloid leukemia (AML) in first complete remission (CR1). From October 1994 to July 1999, 20 patients (median age 9.9 years, range 0.11-16.2) were treated in six centers. Eighteen had de novo AML and two had secondary AML. According to BFM criteria, 10 were classified as standard- and 10 as high-risk patients, respectively. The median time from diagnosis to CR1 and from diagnosis to Auto-HSCT were 1.1 months (range 0.8-1.6) and 4.3 months (range 3.1-6.2), respectively. Purging with either mafosfamide (three) or in vivo interleukin-2 (four) was performed in seven of 20 patients. Melphalan was administered at a dosage of 150-220 mg/m(2) (median 180). Median total number of nucleated cells infused was 2.5 x 10(8)/kg (range 1.1-8.9). The myeloablative regimen was well tolerated with no toxic death, veno-occlusive disease or life-threatening complications. All patients had hematopoietic recovery in a median time of 27 days for neutrophils and 44 days for platelets. Eight of 20 patients relapsed after a median time of 7.2 months from transplant (range 5.7-15.9). Six of them died (five of progression of disease and one of sepsis) while the remaining two patients are alive in CR2. The 3-year cumulative probability of survival and event-free-survival (EFS) is 62% and 56%, respectively. This study showed that in pediatric patients with AML consolidation of CR1 with high-dose melphalan allows survival and EFS to be obtained comparable to other auto-HSCT or chemotherapy published series with a potential sparing effect both on duration of treatment (with respect to chemotherapy) and on long-term side-effects (with respect to auto-HSCT with TBI or busulfan containing regimens).


Subject(s)
Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Melphalan/therapeutic use , Adolescent , Antineoplastic Agents, Alkylating/therapeutic use , Bone Marrow Purging/methods , Child , Child, Preschool , Combined Modality Therapy , Cyclophosphamide/analogs & derivatives , Cyclophosphamide/therapeutic use , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Infant , Interleukin-2/therapeutic use , Italy , Leukemia, Myeloid, Acute/classification , Leukemia, Myeloid, Acute/genetics , Leukemia, Myeloid, Acute/mortality , Male , Melphalan/adverse effects , Patient Selection , Retrospective Studies , Survival Rate , Transplantation, Autologous
7.
J Clin Oncol ; 19(1): 183-90, 2001 Jan 01.
Article in English | MEDLINE | ID: mdl-11134211

ABSTRACT

PURPOSE: To report on the treatment of patients with newly diagnosed neuroblastoma presenting with spinal cord compression (SCC). PATIENTS AND METHODS: Of 1,462 children with neuroblastoma registered between 1979 and 1998, 76 (5.2%) presented with signs/symptoms of SCC, including motor deficit in 75 patients (mild in 43, moderate in 22, severe [ie, paraplegia] in 10), pain in 47, sphincteric deficit in 30, and sensory loss in 11. Treatment of SCC consisted of radiotherapy in 11 patients, laminectomy in 32, and chemotherapy in 33. Laminectomy was more frequently performed in cases with favorable disease stages and in those with severe motor deficit, whereas chemotherapy was preferred in patients with advanced disease. RESULTS: Thirty-three patients achieved full neurologic recovery, 14 improved, 22 remained stable, and eight worsened, including three who become paraplegic. None of the 10 patients with grade 3 motor deficit, eight of whom were treated by laminectomy, recovered or improved. In the other 66 patients, the neurologic response to treatment was comparable for the three therapeutic modalities. All 11 patients treated by radiotherapy and 26 of 32 patients treated by laminectomy, but only two of 33 treated by chemotherapy, received additional therapy for SCC. Fifty-four of 76 patients are alive at time of the analysis, with follow-up of 4 to 209 months (median, 139 months). Twenty-six (44%) of 54 survivors have late sequelae, mainly scoliosis and sphincteric deficit. CONCLUSION: Radiotherapy, laminectomy, and chemotherapy showed comparable ability to relieve or improve SCC. However, patients treated with chemotherapy usually did not require additional therapy, whereas patients treated either with radiotherapy or laminectomy commonly did. No patient presenting with (or developing) severe motor deficit recovered or improved. Sequelae were documented in 44% of surviving patients.


Subject(s)
Neuroblastoma/pathology , Neuroblastoma/therapy , Spinal Cord Compression/therapy , Spinal Cord Neoplasms/pathology , Spinal Cord Neoplasms/therapy , Adolescent , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Infant, Newborn , Laminectomy , Male , Neoplasm Invasiveness , Neuroblastoma/mortality , Spinal Cord Compression/drug therapy , Spinal Cord Compression/radiotherapy , Spinal Cord Neoplasms/mortality , Survival Rate , Treatment Outcome
8.
Cancer ; 89(6): 1396-401, 2000 Sep 15.
Article in English | MEDLINE | ID: mdl-11002236

ABSTRACT

BACKGROUND: Pleuropulmonary blastoma (PPB) is a rare and aggressive malignant tumor that affects children and adults. This neoplasm is histologically characterized by primitive blastema and a malignant mesenchymal stroma that often demonstrates multidirectional differentiation. Despite the introduction of multimodal therapy, the prognosis of patients with PPB remains poor. METHODS: In the current study the authors reported on PPB cases from a national retrospective search performed in 18 Italian Associations for Pediatric Hematology and Oncology centers. Clinical data, surgical notes, pathologic findings, and summaries of chemotherapy and radiotherapy were obtained from reports and correlated with outcome by standard statistical methods. RESULTS: The series included 11 patients (7 boys and 4 girls) with a median age of 32 months. Respiratory distress was the most common clinical symptom. In three patients the PPB developed from other primary dysplastic diseases: cystic adenomatoid malformation in one case and congenital lung cysts in the other two cases. Five patients experienced disease recurrences (local recurrence in three patients and distant metastasis in two patients, within the central nervous system and an intraocular location, respectively). Patients with a type 2 histologic pattern and/or pleural involvement were found to have a worse outcome compared with patients without such features. Event free survival at 2 years from the time of diagnosis was 45% for all patients. Overall survival at 2 years was 72% for all patients. CONCLUSIONS: PPB is an aggressive neoplasm of early childhood and to the authors' knowledge no adequate therapy has been defined to date for patients with PPB. After making the diagnosis, the main goal of therapy should be radical surgery, even in patients with microscopic residual disease. Because the response to chemotherapy is poor, the authors' experience suggests that chemotherapy should be given with local radiotherapy in the majority of patients.


Subject(s)
Lung Neoplasms/therapy , Pleural Neoplasms/therapy , Pulmonary Blastoma/therapy , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Male , Pleural Neoplasms/diagnosis , Pleural Neoplasms/pathology , Prognosis , Pulmonary Blastoma/diagnosis , Pulmonary Blastoma/pathology , Survival Analysis , Treatment Outcome
9.
J Pediatr Surg ; 35(1): 88-91, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10646781

ABSTRACT

BACKGROUND/PURPOSE: The growing use of routine ultrasonography during pregnancy is leading to an increasing number of prenatally diagnosed neuroblastomas. Optimal strategy has not yet been defined for these patients, because knowledge on this particular neuroblastoma (NB) population is still limited. However, definite guidelines are needed to avoid inadequate treatment. The authors analyzed the cases of antenatally detected NB (ADNB) reported in the Italian Neuroblastoma Registry during the past 6 years to elucidate the features of this subset of NB. METHODS: The Italian Neuroblastoma Registry was reviewed for the period January 1993 to December 1998 to collect clinical, radiographic, surgical, and histopathological data on ADNB cases. NB stage was evaluated according to INSS criteria. All patients had undergone imaging (computed tomography or magnetic resonance imaging) of the primary tumor and bone marrow biopsy before surgical resection. RESULTS: Seventeen patients were identified. Primary tumour site was adrenal glands in 16 cases and retroperitoneal ganglia in 1. Stage distribution was stage I, 13 cases; stage II-A, 1 case; stage II-B, 1 case; stage IV-S, 2 cases. All cases underwent primary tumour resection. Mean age at surgery was 4 weeks. Resection of primary tumor was radical in 16 cases, partial in 1. All tumors were characterised by favourable histology according to Shimada classification. N-myc gene amplification was studied in 14 patients. N-myc amplification was detected only in a newborn with stage II-A NB, who died of massive bleeding 2 days after tumor resection. DNA index and 1p deletion were studied in 11 and 8 patients, respectively. Both diploidy and deletion of 1p were observed in a newborn who subsequently died of disease progression despite surgery, chemotherapy, and radiation therapy. Fourteen of 17 patients currently are alive and free of disease, and one with IV-S NB and short follow-up is alive with disease. CONCLUSIONS: Our data give evidence that in most cases infants with ADNB represent a subset of patients with excellent outcome. Aggressive treatment may not always be necessary. Infants with ADNB with unfavorable features should undergo early surgical excision, whereas patients with favourable features could be observed awaiting spontaneous regression of the mass, reserving delayed surgery for tumors that increase in size or do not regress.


Subject(s)
Adrenal Gland Neoplasms/diagnosis , Neuroblastoma/diagnosis , Prenatal Diagnosis , Adrenal Gland Neoplasms/congenital , Adrenal Gland Neoplasms/genetics , Adrenal Gland Neoplasms/surgery , Female , Follow-Up Studies , Gene Deletion , Genes, myc , Humans , Infant , Infant, Newborn , Neuroblastoma/congenital , Neuroblastoma/genetics , Neuroblastoma/surgery , Ploidies , Pregnancy , Retroperitoneal Neoplasms/congenital , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/genetics , Retroperitoneal Neoplasms/surgery , Retrospective Studies , Ultrasonography, Prenatal
10.
Pediatr Med Chir ; 20(1): 33-7, 1998.
Article in Italian | MEDLINE | ID: mdl-9658419

ABSTRACT

We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.


Subject(s)
beta-Thalassemia/therapy , Bone Marrow Transplantation , Child , Child, Preschool , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Female , Humans , Hypogonadism/etiology , Infant , Iron Chelating Agents/administration & dosage , Male , Splenectomy , beta-Thalassemia/diagnosis
11.
Eur J Cancer ; 31A(4): 612-5, 1995.
Article in English | MEDLINE | ID: mdl-7576980

ABSTRACT

Based upon phase I and II studies of deferoxamine alone and in combination with cytotoxic agents cyclophosphamide, etoposide, carboplatin, and thiotepa (D-CECaT), we initiated a single arm multicentre trial in 1992 for advanced neuroblastoma. 57 of 65 patients who entered the trial were evaluable. Following 4 courses of the D-CECaT, almost all the patients underwent surgery. Toxicity was moderate and mainly reversible myelosuppression. The post-surgically defined responses in stage 3 high risk, stage 4 moderate risk and stage 4 high risk patients included 24 complete responses, 26 partial responses, and 3 minor responses, and 4 patients had progressive disease. These patients are being followed to determine the impact of this programme on their overall survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neuroblastoma/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carboplatin/administration & dosage , Carboplatin/adverse effects , Chemotherapy, Adjuvant , Child , Child, Preschool , Cyclophosphamide/administration & dosage , Cyclophosphamide/adverse effects , Deferoxamine/administration & dosage , Deferoxamine/adverse effects , Etoposide/administration & dosage , Etoposide/adverse effects , Humans , Infant , Neoplasm Staging , Neuroblastoma/pathology , Neuroblastoma/surgery , Risk Factors , Thiotepa/administration & dosage , Thiotepa/adverse effects
12.
Pediatr Med Chir ; 16(1): 95-9, 1994.
Article in Italian | MEDLINE | ID: mdl-8029102

ABSTRACT

This is a case report of bilateral nephroblastomatosis in a 19 month child, who underwent a unilateral nephrectomy and chemotherapy. Further review of the nephrectomy specimen and biopsies of the contralateral kidney revealed mature features of nephrogenic rests progressing to Wilms' tumor. We have reviewed the literature and discuss the presentation and different therapeutic approaches.


Subject(s)
Kidney Neoplasms , Neoplasms, Multiple Primary , Wilms Tumor , Child , Child, Preschool , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Infant , Infant, Newborn , Kidney Neoplasms/therapy , Male , Wilms Tumor/therapy
13.
Med Pediatr Oncol ; 23(1): 8-13, 1994.
Article in English | MEDLINE | ID: mdl-8177149

ABSTRACT

A multicentric retrospective study on leukemic ophthalmopathy (LO) is reported. It includes 21 patients, 16 males and 5 females, with acute leukemia (AL) observed in 10 SIOP centers. LO developed in three patients at the time of diagnosis of AL; five patients were in first complete remission (three off therapy); four patients were in second or third remission; and nine were in combined relapse. Most frequent symptoms were blurred vision, photophobia, and ocular pain. Two patients with acute nonlymphoblastic leukemia died before treatment; another underwent bone marrow transplantation; one patient with B-cell acute lymphoblastic leukemia (B-ALL) treated with chemotherapy and radiotherapy died 4 months after LO; the remaining 17 children were treated according to different schedules with (10) or without (7) radiotherapy on the affected eye. Twelve patients achieved ocular remission and four of these had a second ocular relapse. Complete remission after LO treatment lasting for more than 3, 7, 24, 29 months was observed in four patients. The authors conclude that cure is possible in patients who had LO in first complete remission treated with chemotherapy and radiotherapy at high dose on the affected eye.


Subject(s)
Eye/pathology , Leukemic Infiltration/therapy , Acute Disease , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Male , Recurrence , Retrospective Studies , Treatment Outcome
14.
J Clin Oncol ; 11(9): 1770-9, 1993 Sep.
Article in English | MEDLINE | ID: mdl-8355044

ABSTRACT

PURPOSE: To define factors that influence outcome in children with localized but unresectable neuroblastoma by retrospective investigation of response to therapy and outcome in 21 Italian institutions. PATIENTS AND METHODS: Of 145 assessable children diagnosed between 1979 and 1990, 77 were treated between 1979 and 1984 with three consecutive standard-dose (SD) protocols, and 68 between 1985 and 1990 with a high-dose (HD) protocol. All protocols included chemotherapy, followed by resection of primary tumor if feasible. If at least partial resection was achieved, consolidation therapy followed, except that from 1985 onward, patients considered disease-free following surgery received no further treatment. RESULTS: Ninety-four of 145 patients (65%) achieved a complete response (CR) or partial response (PR) with chemotherapy and 75 (52%) subsequently underwent complete resection of the primary tumor. Eighty-one patients are alive (73 without disease, eight with disease), 63 have died, and one is lost to follow-up. The 5-year overall survival (OS) rate is 55% and progression-free survival (PFS) rate 50%. Both OS and PFS correlated with response to chemotherapy, removal of primary tumor, HD therapy, and serum lactate dehydrogenase (LDH) levels. Infants (< 1 year), independent of primary tumor site, and children aged 1 to 15 years with a nonabdominal primary tumor, did better compared with children aged 1 to 15 years with an abdominal primary tumor (PFS, 72% and 64% v 30%; P < .001 and < .01, respectively). Outcome of this last group improved with the HD protocol (PFS, 40% v 23%; P = .01). CONCLUSION: In children with unresectable neuroblastoma, risk categories can be defined by age and primary tumor site. HD chemotherapy should be investigated for the poor-risk category age 1 to 15 years with an abdominal primary tumor.


Subject(s)
Neuroblastoma/therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Multivariate Analysis , Neoplasm Staging , Neuroblastoma/drug therapy , Neuroblastoma/pathology , Neuroblastoma/surgery , Remission Induction , Survival Analysis , Treatment Outcome
15.
J Clin Oncol ; 10(12): 1870-8, 1992 Dec.
Article in English | MEDLINE | ID: mdl-1453202

ABSTRACT

PURPOSE: The objective of the present study was to determine whether an increase in the intensity of therapy improves outcome for children with disseminated poor-risk neuroblastoma. PATIENTS AND METHODS: From January 1982 through November 1989, 181 children 1 year or older with newly diagnosed disseminated neuroblastoma were entered onto two consecutive studies of the Italian Cooperative Group for Neuroblastoma (ICGNB): 75 (study NB82) were enrolled from 1982 to 1984 and were treated with standard-dose (SD) chemotherapy, and 106 (study NB85) were enrolled from 1985 to 1989 and received high-dose (HD) chemotherapy. In both treatment protocols, induction therapy included peptichemio and cisplatin (at SD or HD, respectively) and removal of the primary tumor. In study NB82, children who achieved complete or partial tumor regression received SD consolidation therapy, and in study NB85 they received three cycles of HD chemotherapy (3cCT) or one cycle of myeloablative therapy (MAT) followed by autologous bone marrow transplantation (ABMT). RESULTS: Compared with group NB82, the NB85 group had significantly fewer failures (no tumor response or disease progression) after administration of peptichemio (9% v 31%; P < .01), had more complete responses (CRs) and partial responses (PRs) both after treatment with cisplatin (60% v 43%; P = .01) and after surgery (76% v 57%; P < .01), and was more likely to have achieved complete excision of the primary tumor (70% v 46%; P < .01). Overall survival (OS) and progression-free survival (PFS) at 5 years were 11% and 9% in NB82, and 27% and 18% in NB85 (P < .01 for both); however, in NB85, relapses occurred even after 5 years of CR, so that PFS curves converge approximately 7 years after diagnosis. Median survival time was 14 months in NB82 and 24 months in NB85. Children in the NB85 group who after achievement of CR were consolidated with 3cCT had a 5-year PFS of 24% compared with 32% of those treated with MAT followed by ABMT (P = .5). CONCLUSION: Intensified therapy improves response rate and prolongs survival of children with disseminated neuroblastoma, although its impact on the eventual cure rate remains to be established.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neuroblastoma/drug therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Child , Child, Preschool , Cisplatin/administration & dosage , Female , Humans , Infant , Male , Neoplasm Staging , Neuroblastoma/secondary , Peptichemio/administration & dosage , Statistics as Topic , Treatment Outcome
16.
Cancer ; 70(6): 1625-33, 1992 Sep 15.
Article in English | MEDLINE | ID: mdl-1516016

ABSTRACT

BACKGROUND: Infants (age 0-11 months) with disseminated neuroblastoma are known to have a better prognosis than older children with the disease, but there is little information regarding factors that influence the outcome of the disease in these patients. METHODS: The authors report a series of 110 infants with disseminated neuroblastoma with disease diagnosed between March 1976 and February 1991 in 21 institutions participating in the Italian Cooperative Group on Neuroblastoma (ICGNB). Of the 110 infants, 34 had Stage IV disease, and 76 had Stage IV-S disease. RESULTS: The 5-year survival probability was 77% for all patients, 71% for those with Stage IV disease, and 81% for those with Stage IV-S disease. Of the 34 infants with Stage IV disease, the 9 who were 5 months or younger at the time of disease diagnosis are all alive (1 with active disease) at 7-143 months after diagnosis, whereas of the 25 infants who were 6-11 months of age at the time of disease diagnosis, 10 have died. Of the 76 infants with Stage IV-S disease, 12/64 who were 5 months of age or younger at the time of disease diagnosis died (mostly of massive hepatomegaly); 9 of these deaths occurred in infants with disease diagnosed before they were 2 months old, whereas 1 death occurred in the 12 infants with disease diagnosed when they were 6-11 months old. Four infants with Stage IV-S disease achieved complete disease remission and subsequently had relapse of disease. High levels of serum LDH and low urinary excretion of vanillylmandelic acid were associated with worse prognosis. CONCLUSIONS: The authors suggest that infants older than 6 months of age who have Stage IV disease require aggressive therapy. For infants with disease diagnosed before they are 2 months old, Stage IV-S disease may have a worse prognosis than Stage IV disease.


Subject(s)
Neuroblastoma/mortality , Neuroblastoma/pathology , Age Factors , Female , Humans , Infant , Male , Neoplasm Staging , Neuroblastoma/secondary , Neuroblastoma/therapy , Prognosis , Retrospective Studies , Survival Analysis
17.
Pediatr Med Chir ; 14(1): 61-5, 1992.
Article in Italian | MEDLINE | ID: mdl-1315963

ABSTRACT

UNLABELLED: A retrospective study on germ cell tumors on children is reported. The purpose of this study was to evaluate some prognostic factors (age, sex, site, histology, treatment) as well as to compare the casistic of Puglia Region with the results of the National literature. 45 patients (30 females, 15 males) aging 2 days-12 years observed in three Pediatric Centres of Bari into 23 years. Primary site of the tumor was: ovary 9, testis 9, sacrococcygeal 16, and others site 11 (head 4, mediastinum 2, pelvis 2, abdomen 2, gluteus 1). HISTOLOGY: teratoma 31, choriocarcinoma 1, embryonal carcinoma 7, endodermal sinus tumor 5, germinoma 1. TREATMENT: surgery 35 patients, surgery+chemotherapy 6, surgery+chemotherapy+radiotherapy 4. Results of treatment: 37 of 41 valuable patients achieved a response (34 complete, 3 partial response); 4 patients had no response. Of the 37 patients that have had a complete or partial remission, 8 subsequently relapsed; of these 8 patients, 5 obtained a second remission after second line therapy, 3 are dead for progressive disease. Better prognosis was observed in children with gonadal tumors treated with surgery alone.


Subject(s)
Neoplasms, Germ Cell and Embryonal/therapy , Child , Child, Preschool , Combined Modality Therapy , Female , Humans , Infant , Infant, Newborn , Italy/epidemiology , Male , Neoplasms, Germ Cell and Embryonal/epidemiology , Prognosis , Retrospective Studies , Treatment Outcome
18.
J Hepatol ; 13(2): 187-91, 1991 Sep.
Article in English | MEDLINE | ID: mdl-1744423

ABSTRACT

The absence of detectable anti-HBc antibodies in some hepatitis B virus (HBV) infected patients may be due to altered core-protein (HBc) sequences. To investigate this possibility we sequenced the pre-C/C-region of HBV isolated from 12 juvenile cancer patients who incurred a nosocomial infection of HBV during chemotherapy but did not develop anti-HBc antibodies or acute cytolytic episodes. The sequences demonstrated the highest sequence homology to the pre-C/C region of a previously cloned HBV genome (subtype ayw) and no deletions or striking mutations were detected. Up to 7 years after infection almost all the survivors developed low titers of anti-HBc antibodies but no clinical signs of hepatic damage. These results suggest that chemotherapy may induce a tolerance status to HBcAg, the most immunogenic HBV protein.


Subject(s)
Hepatitis B Antibodies/blood , Hepatitis B Core Antigens/immunology , Hepatitis B/immunology , Neoplasms/drug therapy , Viral Core Proteins/chemistry , Base Sequence , Child , Child, Preschool , Drug-Related Side Effects and Adverse Reactions , Hepatitis B/etiology , Hepatitis B virus/isolation & purification , Humans , Molecular Sequence Data , Neoplasms/complications , Polymerase Chain Reaction , Sequence Homology, Nucleic Acid
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