RESUMO
Wilms tumor is the most common pediatric renal cancer, and lungs represent the major site of metastasis and recurrence. Relapse occurs in 15%, months or years after treatment; so due to the small sample, acquiring more data about the pattern of lung relapse remains a challenge. The aim of our study was to evaluate if pulmonary relapse, detected by computed tomography (CT), occurred at the initial site of lung metastases or in a different location. According to our data, the CT pattern of lung relapse showed high probability of recurrence at the same site of initial metastasis.
Assuntos
Neoplasias Renais , Neoplasias Pulmonares , Tumor de Wilms , Criança , Humanos , Recidiva Local de Neoplasia , Tumor de Wilms/patologia , Neoplasias Renais/patologia , Neoplasias Pulmonares/secundário , Pulmão/patologiaRESUMO
Germ cell tumors (GCTs) are a heterogeneous group of pediatric cancers. In up to one-third of male patients, a primary mediastinal location is associated with the presence of Klinefelter syndrome (KS). We describe a case of mediastinal GCT in a patient, with unacknowledged KS, that presented a relapse 7 years from diagnosis, that is, 2 years after the end of the follow-up program usually recommended for patients with GCT. There are no recommendations for screening for KS in patients with mediastinal GCT and there are no specific guidelines for surveillance of GCT in KS patients. Our experience suggests that KS should be suspected in patients with mediastinal GCT, and a longer follow-up plan should be implemented when GCT occurs in patients with KS.
Assuntos
Síndrome de Klinefelter , Neoplasias do Mediastino , Neoplasias Embrionárias de Células Germinativas , Criança , Humanos , Masculino , Síndrome de Klinefelter/complicações , Síndrome de Klinefelter/diagnóstico , Recidiva Local de Neoplasia , Neoplasias do Mediastino/complicações , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/patologia , Neoplasias Embrionárias de Células Germinativas/complicações , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Doença CrônicaRESUMO
BACKGROUND: Rhabdomyosarcoma (RMS) is an aggressive malignancy, and 20% of children present with metastases at diagnosis. Patients presenting with disseminated disease very occasionally have no clear evidence of a primary tumor mass. As these patients have rarely been investigated, we report on a series of patients with RMS and unknown primary tumor site registered in the Metastatic (MTS) RMS 2008 protocol (October 2008 to December 2016) coordinated by the European pediatric Soft tissue sarcoma Study Group. METHODS: Patients were administered nine cycles of induction chemotherapy, and 48 weeks of maintenance chemotherapy. Surgery and/or radiotherapy were planned after the first assessment of tumor response, and implemented after six cycles of chemotherapy. If feasible, radiotherapy to all sites of metastasis was recommended. RESULTS: We identified 10 patients with RMS and unknown primary site, most of them adolescents (median age 15.8 years, range: 4.6-20.4). Nine had fusion-positive alveolar RMS. Multiple organ involvement was identified in seven patients, two only had bone marrow disease, and one only had leptomeningeal dissemination. All patients were given chemotherapy, four were irradiated, and none had surgery. Three patients underwent allogeneic bone marrow transplantation. At the time of this analysis, only two patients are alive in complete remission: one had received radiotherapy; and one had a bone marrow transplant. CONCLUSIONS: RMS with unknown primary tumor occurs mainly in adolescents and is typically fusion-positive alveolar. Radiotherapy may be important, but survival is poor and patients should be offered enrollment in investigational trials.
Assuntos
Neoplasias Primárias Desconhecidas , Rabdomiossarcoma Alveolar , Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Criança , Adolescente , Humanos , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Rabdomiossarcoma/patologia , Rabdomiossarcoma Embrionário/tratamento farmacológico , Rabdomiossarcoma Alveolar/patologiaRESUMO
BACKGROUND: Irinotecan is a drug active against pediatric sarcomas with a toxicity profile that theoretically allows for its association with more myelotoxic drugs. We examined the feasibility of a dose-density strategy integrating irinotecan in standard chemotherapy regimens for patients with high-risk sarcomas. METHODS: Between November 2013 and January 2020, 23 patients ≤25 years old were included in the study. Eleven patients newly diagnosed with metastatic disease received nine cycles of IrIVA (irinotecan-ifosfamide-vincristine-actinomycin D; ifosfamide 3 g/m2 on days 1 and 2, vincristine 1.5 mg/m2 on day 1, actinomycin D 1.5 mg/m2 on day 1, irinotecan 20 mg/m2 for 5 consecutive days starting on day 8) as first-line therapy. Two relapsed patients received IrIVA and 10 IrVAC (irinotecan-vincristine-actinomycin D-cyclophosphamide; cyclophosphamide 1.5 g/m2 on day 1 instead of ifosfamide). Feasibility was assessed in terms of toxicity and time to complete the treatment. RESULTS: Seventeen rhabdomyosarcomas, four Ewing sarcomas, two desmoplastic small round cell tumors received a total of 181 cycles (range 2-10). Grade 4 neutropenia occurred in 62.4% of the cycles. Thirteen patients had febrile neutropenia. Diarrhea occurred in 14 cycles. The median time to complete the treatment was 195 days (range 170-231), 83.4% of cycles were administered on time or with a delay <1 week. With a median follow-up of 2.6 years (range 0.2-5.0), 12 patients are alive, nine complete remissions, three with the disease. CONCLUSIONS: A dose-density strategy combining irinotecan with standard chemotherapy is feasible. This approach will be investigated in the next trial coordinated by the European pediatric Soft tissue sarcoma Study Group.
Assuntos
Irinotecano/uso terapêutico , Sarcoma , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida/uso terapêutico , Dactinomicina/uso terapêutico , Doxorrubicina/uso terapêutico , Etoposídeo/uso terapêutico , Humanos , Ifosfamida/uso terapêutico , Sarcoma/tratamento farmacológico , Vincristina/efeitos adversosRESUMO
PROCEDURE: The survival of children with rhabdomyosarcoma (RMS) has gradually improved as a result of the adoption of multidisciplinary treatments. Dedicated skills and facilities are indispensable and more readily available at reference centers. In this study, we examined the role of centers' experience (based on the number of patients treated) in their management of patients with RMS. METHODS: We analyzed 342 patients with localized RMS enrolled in the European RMS 2005 protocol from October 2005 to December 2016 at 31 Italian centers that are part of the Soft Tissue Sarcoma Committee (STSC). We grouped the centers by the number of patients each one enrolled (Group 1: >40; Group 2: <40 and >10; and Group 3: <10), and compared a number of indicators to assess the appropriateness of patients' diagnostic workup and treatment and their survival. RESULTS: Overall, 74.6% of patients were treated at 10 centers, and only three of them classifiable as high-volume centers. Only minor differences emerged between the three patient groups in terms of diagnostic investigations and treatment modalities. Survival was similar in the three groups. Approximately, one in four children treated at the centers in Groups 2 and 3 traveled to another center for surgery or radiotherapy. CONCLUSION: Patients treated at STSC centers with different amounts of experience had similar results in terms of survival. This is attributable to all centers in the network adhering to protocol recommendations and receiving the STSC's support on diagnostics and multidisciplinary treatments for RMS.
Assuntos
Rabdomiossarcoma Embrionário , Rabdomiossarcoma , Neoplasias de Tecidos Moles , Criança , Humanos , Itália , Rabdomiossarcoma/cirurgia , Neoplasias de Tecidos Moles/terapiaRESUMO
PURPOSE: To evaluate clinical features at diagnosis, prognostic factors, and outcomes of malignant sacrococcygeal germ cell tumors (SC-GCTs) in patients enrolled in the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) TCG 2004 protocol. PATIENTS AND METHODS: A prospective analysis was conducted on all consecutive patients diagnosed with malignant SC-GCTs between January 2004 and May 2017. Patients with stage I underwent surgery and subsequent surveillance, the others received pediatric cisplatinum-etoposide-bleomycin (pPEB) regimen and eventual deferred surgery. RESULTS: Of 45 patients, 35 were females. Age at diagnosis ranged from 1 day to 3.6 years (median 1.6 years); 26 were stage IV. Of 38 patients who underwent surgery, pathology revealed yolk sac tumor (YST) in 27 and teratoma + YST/embryonal carcinoma in 11, while seven patients were diagnosed based on imaging and elevated levels of alpha-fetoprotein (AFP). Of six patients approached with surgery, only one relapsed and was rescued with first-line chemotherapy. Overall, 38 out of 45 achieved complete remission, three a partial remission, and four were resistant. Ten out of 41 patients who entered remission later relapsed and nine were rescued with a second-line treatment. We observed a global failure percentage of 31% and a 5-year overall survival (OS) and event-free survival (EFS) of 95% and 69%, respectively. CONCLUSIONS: Chemotherapyis generally effective in malignant SC-GCTs, even though almost one-third of our patients experienced events salvageable with second-line treatment. Most of the relapses occurred within 1 year from diagnosis. A close follow up with serial AFP level monitoring should be done for at least 2 years after diagnosis.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Região Sacrococcígea/patologia , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Prognóstico , Estudos Prospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The prognosis for patients with relapsed rhabdomyosarcoma (RMS) depends on a number of variables, including tumor characteristics, type of relapse, and treatment received. All published studies have considered tumor characteristics at initial diagnosis, but not at the time of recurrence. In this study, we compared tumor characteristics at diagnosis and at the moment of local relapse to better define the chance of cure in this group of patients. METHODS: We first analyzed 92 children with localized RMS treated according to the RMS96 and RMS2005 protocols who developed relapse after achieving complete remission at the end of treatment. Then we restricted our analysis to 51 patients with local recurrence to compare their initial tumor characteristics with those at relapse. All characteristics were studied using univariate and multivariate analyses. RESULTS: The 10-year progression-free survival (PFS) and overall survival (OS) rates for the whole group were 23.5% (15.4-32.6) and 34.4% (24.8-44.1), respectively. On multivariate analysis, only primary tumor site appeared to have a strong impact on prognosis (P = .0010). The 10-year PFS and OS rates of patients with locoregional recurrences were 22.7% (12.3-35.0) and 34.9% (22.1-47.9), respectively. Multivariate analysis showed that tumors at unfavorable sites (P = .0044), and tumor size > 5 cm at recurrence (P = .0088) were associated with the poorest prognosis. CONCLUSION: Our study demonstrates that to estimate the chance of cure in patients with relapsed RMS, we should also consider tumor characteristics at the time of relapse, and tumor size in particular.
Assuntos
Recidiva Local de Neoplasia/mortalidade , Rabdomiossarcoma/mortalidade , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Prognóstico , Estudos Retrospectivos , Rabdomiossarcoma/patologia , Rabdomiossarcoma/cirurgia , Taxa de SobrevidaRESUMO
Schimke immuno-osseous dysplasia (SIOD) is a rare multisystemic disorder with a variable clinical expressivity caused by biallelic variants in SMARCAL1. A phenotype-genotype correlation has been attempted and variable expressivity of biallelic SMARCAL1 variants may be associated with environmental and genetic disturbances of gene expression. We describe two siblings born from consanguineous parents with a diagnosis of SIOD revealed by whole exome sequencing (WES). Results: A homozygous missense variant in the SMARCAL1 gene (c.1682G>A; p.Arg561His) was identified in both patients. Despite carrying the same variant, the two patients showed substantial renal and immunological phenotypic differences. We describe features not previously associated with SIOD-both patients had congenital anomalies of the kidneys and of the urinary tract and one of them succumbed to a classical type congenital mesoblastic nephroma. We performed an extensive characterization of the immunophenotype showing combined immunodeficiency characterized by a profound lymphopenia, lack of thymic output, defective IL-7Rα expression, and disturbed B plasma cells differentiation and immunoglobulin production in addition to an altered NK-cell phenotype and function. Conclusions: Overall, our results contribute to extending the phenotypic spectrum of features associated with SMARCAL1 mutations and to better characterizing the underlying immunologic disorder with critical implications for therapeutic and management strategies.
Assuntos
Arteriosclerose , DNA Helicases , Rim , Células Matadoras Naturais/imunologia , Mutação de Sentido Incorreto , Nefroma Mesoblástico , Síndrome Nefrótica , Osteocondrodisplasias , Fenótipo , Doenças da Imunodeficiência Primária , Embolia Pulmonar , Sistema Urinário , Substituição de Aminoácidos , Arteriosclerose/diagnóstico por imagem , Arteriosclerose/genética , Arteriosclerose/imunologia , DNA Helicases/genética , DNA Helicases/imunologia , Feminino , Humanos , Subunidade alfa de Receptor de Interleucina-7/genética , Subunidade alfa de Receptor de Interleucina-7/imunologia , Rim/anormalidades , Rim/diagnóstico por imagem , Rim/imunologia , Masculino , Nefroma Mesoblástico/diagnóstico por imagem , Nefroma Mesoblástico/genética , Nefroma Mesoblástico/imunologia , Síndrome Nefrótica/diagnóstico por imagem , Síndrome Nefrótica/genética , Síndrome Nefrótica/imunologia , Osteocondrodisplasias/diagnóstico por imagem , Osteocondrodisplasias/genética , Osteocondrodisplasias/imunologia , Doenças da Imunodeficiência Primária/diagnóstico por imagem , Doenças da Imunodeficiência Primária/genética , Doenças da Imunodeficiência Primária/imunologia , Embolia Pulmonar/diagnóstico por imagem , Embolia Pulmonar/genética , Embolia Pulmonar/imunologia , Sistema Urinário/anormalidades , Sistema Urinário/diagnóstico por imagem , Sistema Urinário/imunologia , Sequenciamento Completo do GenomaRESUMO
INTRODUCTION: The treatment paradigm in desmoid-type fibromatosis (DF) has changed in recent years from a surgery-based strategy to a multidisciplinary approach that includes systemic therapies. Among various medical therapies, hydroxyurea has been considered of potential interest. This case series summarizes the experience gained at four centers using hydroxyurea in relapsing DF. METHODS: Eligibility requirements were age < 21 years, histologically confirmed DF, and progressive or recurrent disease after at least one line of systemic therapy. Hydroxyurea was given orally at an initial dose of 20 mg/kg/day (escalated up to 30 mg/kg/day as necessary, if well tolerated). RESULTS: The series included 16 patients treated between 2008 and 2016. Hydroxyurea was the second systemic therapy in nine cases, and the third (at least) in seven. There was no reported G3-G4 hematological toxicity, and one case of G3 diarrhea. Dose reductions were reported in three cases (due to G2 neutropenia). The response rate was 18.7% major partial remissions, 37.5% considering any amount of shrinkage, 68.7% considering symptom response or signs of tissue response as well. In patients with no progression, the treatment was continued for 9-24 months. CONCLUSION: This is the first published series on the efficacy of hydroxyurea in pediatric DF. The response rate was moderate, but similar to that reported for other medical therapies currently considered as treatment options in this disease. Though further, larger series are needed to confirm as much, hydroxyurea has potential as an effective alternative therapy for DF.
Assuntos
Antineoplásicos/uso terapêutico , Fibromatose Agressiva/cirurgia , Hidroxiureia/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Progressão da Doença , Feminino , Seguimentos , França/epidemiologia , Humanos , Incidência , Lactente , Masculino , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Adulto JovemRESUMO
BACKGROUND: Rhabdomyosarcoma (RMS) occurring at nonparameningeal head and neck (NPM-HN) sites carries a better prognosis than parameningeal RMS and some other sites. We analyzed the treatments administered and results obtained in patients with localized NPM-HN RMS, included in the protocols coordinated by the Italian Soft Tissue Sarcoma Committee (STSC), in an effort to identify prognostic factors that could facilitate the tailoring of treatment. METHODS: Sixty-six patients up to 18 years of age with previously untreated, localized NPM-HN RMS were prospectively registered in three consecutive protocols: RMS79, RMS88, and RMS96. Primary surgery was recommended when complete tumor resection was deemed feasible without mutilations. In other cases, only a biopsy was performed, followed by chemotherapy and delayed surgery and/or radiotherapy (RT). RESULTS: NPM-HN RMS showed favorable characteristics: 72.7% were <5 cm, 72.7% were T1, and 80.3% were N0. With a median follow-up of 16 years (range 7-27), the 10-year progression-free survival and overall survival for the whole group were 65.1% (confidence interval [CI]: 52.3-75.3) and 74.2% (CI: 61.8-83.1). Progressive improvement has been seen in the successive protocols. Age and RT emerged as independent prognostic factors. The group of young children (age Assuntos
Neoplasias de Cabeça e Pescoço/terapia
, Rabdomiossarcoma/terapia
, Adolescente
, Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Criança
, Pré-Escolar
, Ensaios Clínicos como Assunto
, Terapia Combinada
, Feminino
, Seguimentos
, Neoplasias de Cabeça e Pescoço/mortalidade
, Humanos
, Lactente
, Recém-Nascido
, Itália
, Estimativa de Kaplan-Meier
, Masculino
, Procedimentos Cirúrgicos Otorrinolaringológicos
, Prognóstico
, Intervalo Livre de Progressão
, Radioterapia
, Rabdomiossarcoma/mortalidade
RESUMO
BACKGROUND: Malignant peripheral nerve sheath tumor (MPNST) is one of the most common nonrhabdomyosarcoma soft tissue sarcomas encountered in pediatric age, and it is generally characterized by poor outcome, particularly for relapsing patients. MATERIALS AND METHODS: This study considered 73 patients <21 years of age with relapsing MPNST observed among 120 patients enrolled in Italian pediatric protocols from 1979 to 2004. With the aim of possibly establishing a risk-adapted stratification, patients' outcome was examined using univariate and multivariate analysis based on clinical features at onset, first-line treatments, clinical findings at the time of first relapse, and second-line treatments. RESULTS: The time to relapse ranged from 1 to 204 months after first diagnosis (median 7 months). The first relapse event was mainly local. At the time of our analysis, nine patients were alive in remission. The median overall survival after first relapse was 11 months, and the survival rates were 39.2% at 1 year and 15.8% at 5 years. The factors revealing the greatest impact on prognosis were as follows: initial tumor invasiveness, time of relapse, and achievement of a secondary complete remission (which was related to the feasibility of radical surgery). CONCLUSIONS: Our study confirmed the unsatisfactory prognosis for pediatric patients with relapsing MPNST and pointed to a risk-adapted stratification model for the purposes of deciding second-line treatments. For the time being, an aggressive surgical approach seems to be the only effective salvage treatment and should be recommended. New therapeutic approaches are under evaluation with a view to improving current outcomes.
Assuntos
Neurilemoma/diagnóstico , Neurilemoma/mortalidade , Neurilemoma/terapia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Invasividade Neoplásica , Neurilemoma/patologia , Prognóstico , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Pediatric nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) may rarely occur in visceral tissues, and little is known about their clinical history. The present study retrospectively analyzed a group of patients prospectively registered in Italian pediatric protocols conducted between 1979 and 2004. METHODS: Inclusion criteria for the study were as follows: a pathological diagnosis of "adult-type NRSTS," arising at visceral sites (lung-pleurae, liver, kidney, and mesentery-bowel); age under 18 years; no previous treatment except for primary surgery; available clinical data; and written consent. RESULTS: Thirty cases with visceral NRSTS were collected and analyzed. Sites of origin were as follows: mesentery-bowel in 12 cases, lung-pleurae in 11, liver in 5, and kidney in 2. According to the Intergroup Rhabdomyosarcoma Study (IRS) surgical grouping system, patients were classified as follows: nine IRS group I, three group II, 12 group III, and six group IV. Patients were treated with a multimodal approach including surgery, radiotherapy, and/or chemotherapy, according to their characteristics. For the series as a whole, the 5-year event-free and overall survival rates were 33.3% and 40.0%, respectively. The IRS group (reflecting the feasibility of initial complete resection) emerged as the main prognostic factor. Survival rates also correlated with tumor size and local invasiveness, histological subtype, and tumor sites (the worst outcome was seen for tumors arising in the lung and pleurae). CONCLUSIONS: This study confirmed that visceral NRSTS are aggressive tumors carrying a worse prognosis than pediatric NRSTS arising in soft tissues of the extremities. Local treatment remains the main challenge for these tumors.
Assuntos
Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Prognóstico , Vísceras/patologiaRESUMO
BACKGROUND: Enhancer of Zeste Drosophila Homologue 2 (EZH2) is a key regulator of transcription as a member of polycomb repressive complex 2 (PRC2) which exerts repression of downstream genes and is correlated to invasiveness and progression of different tumours. Therefore, we evaluated the expression of PRC2 proteins in pediatric soft tissue sarcoma (rhabdomyosarcoma, RMS and extraosseous Ewing sarcoma, EES) correlating them to the clinical outcome of the patients. METHODS: We analyzed PRC2 protein expression by quantitative real time PCR, western blotting and immunohistochemistry in 17 soft tissue sarcomas (11 RMS and 6 EES) enrolled at Paediatric Oncology Units of the Second University of Naples. Expression analysis was performed for EZH2, SUZ12 and EED. RESULTS: Enhancer of Zeste Drosophila Homologue 2 was expressed with a different degree in 60 % of samples. Interestingly, the magnitude of EZH2 up regulation was significantly higher in patients presenting lymph node and/or distant metastases at the diagnosis. Moreover, patients overexpressing EZH2 had a lower probability of survival compared to patients negative or with low EZH2 expression. CONCLUSIONS: Our study suggests that high EZH2 expression is associated to increased aggressiveness of the disease. Therefore, drugs that control its activity could be potentially used in the epigenetic target treatment of tumors with these alterations.
RESUMO
Objective: The incidence of Wilms' tumor (WT) among adult individuals accounts for less than 1% of kidney cancer cases, with a prognosis usually less favorable when compared to younger individuals and an overall survival rate of 70% for the adult patients versus 90% for the pediatric cases. The diagnosis and treatment of WT are complex in the preoperative setting; neoadjuvant chemotherapy (NAC) or robotic surgery has rarely been described. This study aimed to review the literature of robotic surgery in WT and report the first adult WT management using both NAC and robotic strategy. Methods: We reported a case of WT managed in a multidisciplinary setting. Furthermore, according to Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations, a systematic review of the literature until August 2020 of WT treated with a robotic approach was carried out. Results: A 33-year-old female had a diagnosis of WT. She was scheduled to NAC, and according to the clinical and radiological response to a robotic radical nephrectomy with aortic lymph nodes dissection, she was managed with no intraoperative rupture, a favorable surgical outcome, and a follow-up of 25 months, which did not show any recurrence. The systematic review identified a total number of 230 cases of minimally invasive surgery reported in the literature for WT. Of these, approximately 15 patients were carried out using robotic surgery in adolescents while none in adults. Moreover, NAC has not been administered before minimally invasive surgery in adults up until now. Conclusion: WT is a rare condition in adults with only a few cases treated with either NAC or minimally invasive approach so far. The advantage of NAC followed by the robotic approach could lead to favorable outcomes in this complex scenario. Notwithstanding, additional cases of adult WT need to be identified and investigated to improve the oncological outcome.
RESUMO
BACKGROUND: In certain rare undifferentiated small round cell sarcomas new specific molecular CIC-DUX4/other partner, BCOR-CCNB3/other partner, YWHAE fusions, or BCOR-ITD (internal tandem duplication) were identified. These new "CIC fused" (CIC-fused/ATXN1::NUTM1) and "BCOR rearranged" (BCOR fused/ITD/ YWHAE) soft tissue sarcomas (STS) are not well described. METHODS: Multi-institutional European retrospective analysis of young patients (0-24 years) with CIC-fused and BCOR rearranged STS. RESULTS: Overall, out of the 60 patients selected, the fusion status was CIC-fused (n = 29), ATXN1::NUTM1 (n = 2), BCOR::CCNB3 (n = 18), BCOR-ITD (n = 7), and YWHAE (n = 3), MAML::BCOR STS (n = 1). The main primaries were abdomen-pelvic (n = 23) and limbs (n = 18). Median age was 14 years (0.9-23.8) and 0.9 (0.1-19.1) for CIC-fused and BCOR-rearranged groups, respectively (n = 29; p < 0.001). IRS stages were I (n = 3), II (n = 7), III (n = 35), and IV (n = 15). Overall, 42 patients had large tumors (>5 cm) but only six had lymph node involvement. Patients received mainly chemotherapy (n = 57), local surgery (n = 50), and/or radiotherapy (n = 34). After a median follow-up of 47.1 months (range, 3.4-230), 33 (52%) patients had an event and 23 patients died. Three-year event-free survivals were 44.0% (95% CI 28.7-67.5) and 41.2% (95% CI 25.4-67.0) for CIC and BCOR groups (p = 0.97), respectively. Three-year overall survivals were 46.3% (95% CI 29.6-72.4) and 67.1% (95% CI 50.4-89.3; p = 0.24), respectively. CONCLUSIONS: Pediatric patients often present with large tumors and metastatic disease, especially CIC sarcomas. Overall outcome is dismal. New treatment options are needed.
Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Criança , Adolescente , Adulto Jovem , Proteínas Repressoras/genética , Estudos Retrospectivos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/análise , Fatores de Transcrição , Sarcoma/genética , Sarcoma/terapia , Biomarcadores Tumorais/análise , Proteínas de Fusão OncogênicaRESUMO
Myositis ossificans circumscripta (MOC) is a benign disease characterized by localized heterotopic bone formation within muscles or soft tissue, usually interesting great muscles of extremities. We report a rare case of unusual location in the neck not associated with previous trauma, mimicking a solid tumor, with well-documented diagnostic imaging features. During COVID-19 pandemic outbreak in Italy, in May 2020, a 14-year-old boy developed a progressive and persistent neck pain on the right side, without known history of trauma. Initial therapy with non-steroid anti-inflammatory drugs and physiokinetic therapy gave only a slight improvement. A neck ultrasound showed an inhomogeneous right neck mass, with posterior shadowing due to calcifications. Computed tomography and magnetic resonance imaging confirmed a huge right neck mass, located in the paravertebral space with peripheral calcifications and mild central contrast enhancement. After surgical excision of the lesion, pathology revealed the presence of muscular tissue mixed with fibroblastic/myofibroblastic proliferation and ossification areas consistent with myositis ossificans. A careful analysis of clinical and radiological features is very important to manage young patients showing progressive pain and swelling of the neck, since MOC can mimic soft tissue or bone tumors, and it should be suspected even in the absence of a known history of trauma.
RESUMO
Liquid biopsy analysis represents a powerful and noninvasive tool to uncover biomarkers for disseminated disease assessment and longitudinal monitoring of patients. Herein, we explored the value of circulating and disseminated tumor cells (CTC and DTC, respectively) and cell-free DNA (cfDNA) in pediatric rhabdomyosarcoma (RMS). Peripheral blood and bone marrow samples were analyzed to detect and enumerate CTC and DTC, respectively. We used the epithelial cellular adhesion molecule (EpCAM)-based CellSearch platform coupled with an automatic device to collect both EpCAM-positive and EpCAM-low/negative CTCs. The standard assay was implemented, including the mesenchymal marker desmin. For selected cases, we molecularly profiled primary tumors and liquid biopsy biomarkers using whole-exome sequencing and droplet digital PCR, respectively. RMS patients with metastatic disease had a significantly higher number of CTCs compared to those with localized disease, whereas DTCs were detected independently of disease presentation. The use of the desmin marker remarkably increased the identification of CTCs and DTCs in RMS samples. Of note, CTC clusters were detected in RMS patients with disseminated disease. Further, cfDNA and CTC molecular features closely reflected the molecular makeup of primary tumors and informed of disease course.
Assuntos
Ácidos Nucleicos Livres , Células Neoplásicas Circulantes , Rabdomiossarcoma , Biomarcadores , Biomarcadores Tumorais/genética , Criança , Desmina/genética , Molécula de Adesão da Célula Epitelial , Humanos , Células Neoplásicas Circulantes/patologia , Rabdomiossarcoma/diagnóstico , Rabdomiossarcoma/genéticaRESUMO
Inflammatory myofibroblastic tumors (IMTs) are locally aggressive malignancies occurring at various sites. Surgery is the mainstay of treatment and prognosis is generally good. For children with unresectable or metastatic tumors, however, outcome is particularly severe, limited also by the lack of predictive biomarkers of therapy efficacy and disease progression. Blood represents a minimally invasive source of cancer biomarkers for real-time assessment of tumor growth, particularly when it involves the analysis of circulating tumor cells (CTC). As CTCs potentially represent disseminated disease, their detection in the blood correlates with the presence of metastatic lesions and may reflect tumor response to treatment. Herein, we present a case report of a 19-year-old boy with an ALK-positive IMT of the bladder, proximal osteolytic and multiple bilateral lung lesions, who received ALK inhibitor entrectinib postoperatively and underwent longitudinal CTC analysis during treatment. Antitumor activity of entrectinib was demonstrated and was accompanied by regression of lung lesions, elimination of CTCs from the blood and no development of relapses afterwards. Therapy continued without any clinical sign of progression and 24 months since the initiation of treatment the patient remains symptom-free and disease-free.
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We describe three children who developed an osteosarcoma after receiving treatment for acute lymphoblastic leukemia, which included an allogeneic bone marrow transplant (BMT). We discuss the therapeutic options. None of the patients responded to conventional chemotherapy, but one patient given regorafenib showed a temporary response. We conclude that osteosarcoma after BMT has an aggressive course and it is worth further investigating multikinase inhibitors in this setting.
Assuntos
Transplante de Medula Óssea/efeitos adversos , Osteossarcoma/secundário , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , MasculinoRESUMO
Pediatric renal cancer is rare, and robust evidence for treatment recommendations is lacking. In the perspective of personalized medicine, clinicians need new biomarkers to improve risk stratification and patients' follow-up. Herein, we analyzed some liquid biopsy tools, which have been never tested in pediatric renal cancer: namely, circulating tumor cells (CTCs); the expression of M30, an apoptosis marker, to test CTC metastatic potential; and c-MET expression in CTCs, because of its role in renal cancer progression and drug-resistance. Furthermore, we evaluated the Circulating Endothelial Cells (CECs), whose utility we previously demonstrated in adult metastatic renal cancer treated with anti-angiogenic therapy. We compared two renal cell carcinomas of clear-cell type, stage I and IV, which underwent surgery and surgery plus Sunitinib, respectively. Baseline CTC level and its changes during follow-up were consistent with patients' outcome. In case 2, stage IV, the analysis of CECs performed during Sunitinib revealed a late response to treatment consistent with poor outcome, as the finding of M30-negative, viable cells. Noteworthily, few CTCs were MET-positive in both cases. Our study highlights the feasibility for a change in the prognostic approach and follow-up of childhood renal cancer, with a view to guide a better treatment design.