RESUMEN
BACKGROUND: Osteosarcoma stratification relies on clinical parameters and histological response. We developed a new personalized stratification using less invasive circulating tumor DNA (ctDNA) quantification. PATIENTS AND METHODS: Plasma from patients homogeneously treated in the prospective protocol OS2006, at diagnosis, before surgery and end of treatment, were sequenced using low-passage whole-genome sequencing (lpWGS) for copy number alteration detection. We developed a prediction tool including ctDNA quantification and known clinical parameters to estimate patients' individual risk of event. RESULTS: ctDNA quantification at diagnosis (diagCPA) was evaluated for 183 patients of the protocol OS2006. diagCPA as a continuous variable was a major prognostic factor, independent of other clinical parameters, including metastatic status [diagCPA hazard ratio (HR) = 3.5, P = 0.002 and 3.51, P = 0.012, for progression-free survival (PFS) and overall survival (OS)]. At the time of surgery and until the end of treatment, diagCPA was also a major prognostic factor independent of histological response (diagCPA HR = 9.2, P < 0.001 and 11.6, P < 0.001, for PFS and OS). Therefore, the addition of diagCPA to metastatic status at diagnosis or poor histological response after surgery improved the prognostic stratification of patients with osteosarcoma. We developed the prediction tool PRONOS to generate individual risk estimations, showing great performance ctDNA quantification at the time of surgery and the end of treatment still required improvement to overcome the low sensitivity of lpWGS and to enable the follow-up of disease progression. CONCLUSIONS: The addition of ctDNA quantification to known risk factors improves the estimation of prognosis calculated by our prediction tool PRONOS. To confirm its value, an external validation in the Sarcoma 13 trial is underway.
Asunto(s)
Biomarcadores de Tumor , Neoplasias Óseas , ADN Tumoral Circulante , Osteosarcoma , Humanos , Osteosarcoma/genética , Osteosarcoma/sangre , Osteosarcoma/patología , Osteosarcoma/cirugía , Osteosarcoma/mortalidad , Osteosarcoma/diagnóstico , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Masculino , Femenino , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/sangre , Neoplasias Óseas/cirugía , Neoplasias Óseas/mortalidad , Adulto , Adolescente , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Estudios Prospectivos , Adulto Joven , Niño , Variaciones en el Número de Copia de ADN , Clasificación del Tumor , Persona de Mediana Edad , Secuenciación Completa del Genoma , Supervivencia sin ProgresiónRESUMEN
BACKGROUND AND AIMS: Prognosis of hepatoblastoma patients has increased with cisplatin-based chemotherapy and high-quality resection including liver transplant. Consequently current risk-adapted therapeutic strategy aims to reduce long-term side effects in patients with standard risk disease. METHODS: We report long-term mortality and morbidity data concerning 151 2-year hepatoblastoma survivors treated with SIOPEL risk-adapted strategies (sex-ratio M/F = 1.6, median age at diagnosis = 2.6 years [range 0-17.7], median year at diagnosis = 2008 [1994-2017]). Fifty-three patients had loco-regional risk factors VPEFR, 12 were PRETEXT-IV and 30 were metastatic. All received cisplatin and 84 anthracyclines. Twelve had liver transplant. To assess hearing, renal and cardiac functions, audiograms were performed in 116/151 patients (76.8%), glomerular filtration rate in 113/151 (74.8%) and cardiac ultrasound in 65/84 (77.4%) anthracycline-exposed patients. RESULTS: With a median follow-up of 9.4 years (range 2.1-25.8), four late relapses, one second malignancy (Acute Myeloid Leukemia AML-M5) and two deaths (one from hepatoblastoma, one from AML) occurred. The 10-years event free survival and overall survival probabilities were 95.5% (95% CI 91.9-99.1) and 98.7% (95% CI 96.8-100), respectively. Sixty-eight non-oncologic health-events included 57 cases of hearing loss (including 25 Brock 3-4), three liver cirrhosis, three pre-operative portal cavernoma, two focal nodular hyperplasia, two grade-1 chronic kidney diseases and one asymptomatic cardiac dysfunction were reported. Ototoxicity was significantly associated with cisplatin cumulative dose (OR = 2.07, 95% CI 1.32-3.24, p = 0.001) and carboplatin exposure (OR = 3.14, 95% CI 1.30-7.58, p = 0.01) in multivariable analysis adjusted for sex and age at diagnosis. CONCLUSIONS: With current risk-adapted strategies, hepatoblastoma is a highly curable disease, with very rare relapses, and few late effects except hearing loss which remains a serious condition in these very young patients.
Asunto(s)
Hepatoblastoma , Neoplasias Hepáticas , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/uso terapéutico , Niño , Preescolar , Cisplatino/efectos adversos , Humanos , Lactante , Recién Nacido , Neoplasias Hepáticas/tratamiento farmacológico , Morbilidad , SobrevivientesRESUMEN
Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum of benign and malignant tumors. Basal cell carcinomas (BCC), odontogenic keratocysts and medulloblastomas are the main tumor types encountered, but meningiomas, ovarian or cardiac fibromas and sarcomas have also been described. The clinical features and tumor risks are different depending on the causative gene. Due to the rarity of this condition, there is little data on phenotype-genotype correlations. This report summarizes genotype-based recommendations for screening patients with PTCH1 and SUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 in PTCH1, and at age 20 in SUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 for PTCH1 PV carriers only. For medulloblastomas, repeated brain MRI from birth to 5 years should be proposed for SUFU PV carriers only. Brain MRI for meningiomas and pelvic ultrasound for ovarian fibromas should be offered to both PTCH1 and SUFU PV carriers. Follow-up of patients treated with radiotherapy should be prolonged and thorough because of the risk of secondary malignancies. Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required.
Asunto(s)
Síndrome del Nevo Basocelular , Neoplasias Cerebelosas , Neoplasias Cutáneas , Síndrome del Nevo Basocelular/diagnóstico , Síndrome del Nevo Basocelular/genética , Neoplasias Cerebelosas/diagnóstico , Neoplasias Cerebelosas/genética , Niño , Preescolar , Proteínas Hedgehog/genética , Humanos , Receptor Patched-1/genética , Proteínas Represoras/genética , Adulto JovenAsunto(s)
Neoplasias Encefálicas , Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN/genética , Síndromes Neoplásicos Hereditarios , Adolescente , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Niño , Colonoscopía , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , ADN Polimerasa II/genética , ADN Polimerasa III/genética , Diagnóstico Diferencial , Asesoramiento Genético , Mutación de Línea Germinal , Guías como Asunto , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Síndrome de Li-Fraumeni/psicología , Lupus Eritematoso Sistémico/genética , Síndromes Neoplásicos Hereditarios/diagnóstico , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/terapia , Países Bajos , Proteínas de Unión a Poli-ADP-Ribosa/genética , Vacunación , Adulto JovenAsunto(s)
Neoplasias Óseas/terapia , Oncología Médica/normas , Osteosarcoma/terapia , Participación del Paciente , Adulto , Cuidados Posteriores/métodos , Cuidados Posteriores/normas , Factores de Edad , Protocolos de Quimioterapia Combinada Antineoplásica/normas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Neoplasias Óseas/diagnóstico , Neoplasias Óseas/epidemiología , Neoplasias Óseas/patología , Huesos/diagnóstico por imagen , Huesos/patología , Huesos/cirugía , Niño , Europa (Continente) , Humanos , Incidencia , Cuidados a Largo Plazo/métodos , Cuidados a Largo Plazo/normas , Imagen por Resonancia Magnética , Oncología Médica/métodos , Terapia Neoadyuvante/métodos , Terapia Neoadyuvante/normas , Estadificación de Neoplasias , Procedimientos Ortopédicos/métodos , Procedimientos Ortopédicos/normas , Osteosarcoma/diagnóstico , Osteosarcoma/epidemiología , Osteosarcoma/patología , Tomografía Computarizada por Tomografía de Emisión de Positrones , Cintigrafía , Radioterapia Adyuvante/métodos , Radioterapia Adyuvante/normas , Grupos de Autoayuda/normas , Sociedades Médicas/normas , Supervivencia , Resultado del TratamientoRESUMEN
The cure rate for childhood and adolescent patients with cancer has currently reached almost 80% and protecting future fertility and thereby promoting quality of life have become a major challenge in the care of these patients (Bioethics Law, 2004). Age, sex and associated treatments influence the risk of future subfertility. Certain chemotherapies (particularly alkylating agents) and radiotherapy fields that include the gonads or hypothalamopituitary axis may negatively impact the future fertility of patients. Evaluation of the gonadotoxic potential of therapeutic measures and the utilization of appropriate methods to preserve fertility require the combined efforts of a multidisciplinary team that includes pediatric oncologists, radiotherapists, surgeons, reproductive physicians and biologists and psychologists. Techniques for fertility preservation vary depending on the age of the child and range from surgical transposition of the gonads for pelvic radiotherapy to cryopreservation of the ovary or testicle in case of sterilizing chemotherapy. While scientists still do not yet fully understand the maturation of immature germ cells, these children will be seeking the assistance of Medically Assisted Procreation (MAP) in 20-30 years. In the meanwhile, it is to be hoped that many more advances will be achieved in the utilization of harvested germinal tissue.
Asunto(s)
Preservación de la Fertilidad/métodos , Infertilidad/prevención & control , Neoplasias/terapia , Adolescente , Factores de Edad , Niño , Preescolar , Femenino , Humanos , Infertilidad/etiología , MasculinoRESUMEN
Most of tumours of the foot are tumour-like (synovial cyst, foreign body reactions and epidermal inclusion cyst) or benign conditions (tenosynovial giant cells tumours, planta fibromatosis). Malignant tumours of the soft-tissue and skeleton are very rare in the foot and their diagnosis is often delayed with referral to specialised teams after initial inappropriate procedures or unplanned excisions. The adverse effect of these misdiagnosed tumours is the increasing rate of amputation or local recurrences in the involved patients. In every lump, imaging should be discussed before any local treatment. Every lesion which is not an obvious synovial cyst or plantar fibromatosis should have a biopsy performed.After the age of 40 years, chondrosarcoma is the most usual malignant tumour of the foot. In young patients bone tumours such as osteosarcoma or Ewing's sarcoma, are very unusually located in the foot. Synovial sarcoma is the most frequent histological diagnosis in soft tissues. Epithelioid sarcoma or clear cell sarcoma, involve more frequently the foot and ankle than other sites. The classic local treatment of malignant conditions of the foot and ankle was below-knee amputation at different levels. Nowadays, with the development of adjuvant therapies, some patients may benefit from conservative surgery or partial amputation after multidisciplinary team discussions.The prognosis of foot malignancy is not different from that at other locations, except perhaps in chondrosarcoma, which seems to be less aggressive in the foot. The anatomy of the foot is very complex with many bony and soft tissue structures in a relatively small space making large resections and conservative treatments difficult to achieve. Cite this article: EFORT Open Rev 2017;2. DOI: 10.1302/2058-5241.2.160078. Originally published online at www.efortopenreviews.org.
RESUMEN
Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.
Asunto(s)
Neoplasias/epidemiología , Adolescente , Investigación Biomédica/organización & administración , Atención a la Salud/organización & administración , Europa (Continente)/epidemiología , Unión Europea , Humanos , Cooperación Internacional , Oncología Médica/organización & administración , Neoplasias/psicología , Neoplasias/terapia , Adulto JovenRESUMEN
BACKGROUND: Constitutional mismatch repair deficiency (CMMRD) syndrome is a childhood cancer predisposition syndrome involving biallelic germline mutations of MMR genes, poorly recognised by clinicians so far. METHODS: Retrospective review of all 31 patients with CMMRD diagnosed in French genetics laboratories in order to describe the characteristics, treatment and outcome of the malignancies and biological diagnostic data. RESULTS: 67 tumours were diagnosed in 31 patients, 25 (37%) Lynch syndrome-associated malignancies, 22 (33%) brain tumours, 17 (25%) haematological malignancies and 3 (5%) sarcomas. The median age of onset of the first tumour was 6.9â years (1.2-33.5). Overall, 22 patients died, 9 (41%) due to the primary tumour. Median survival after the diagnosis of the primary tumour was 27â months (0.26-213.2). Failure rate seemed to be higher than expected especially for T-cell non-Hodgkin's lymphoma (progression/relapse in 6/12 patients). A familial history of Lynch syndrome was identified in 6/23 families, and consanguinity in 9/23 families. PMS2 mutations (n=18) were more frequent than other mutations (MSH6 (n=6), MLH1 (n=4) and MSH2 (n=3)). CONCLUSIONS: In conclusion, this unselected series of patients confirms the extreme severity of this syndrome with a high mortality rate mostly related to multiple childhood cancers, and highlights the need for its early detection in order to adapt treatment and surveillance.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Colorrectales/diagnóstico , Síndromes Neoplásicos Hereditarios/diagnóstico , Proteínas Adaptadoras Transductoras de Señales/genética , Adenosina Trifosfatasas/genética , Adolescente , Adulto , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/terapia , Niño , Preescolar , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/terapia , Enzimas Reparadoras del ADN/genética , Proteínas de Unión al ADN/genética , Femenino , Humanos , Lactante , Masculino , Endonucleasa PMS2 de Reparación del Emparejamiento Incorrecto , Homólogo 1 de la Proteína MutL , Proteína 2 Homóloga a MutS/genética , Mutación , Síndromes Neoplásicos Hereditarios/genética , Síndromes Neoplásicos Hereditarios/terapia , Proteínas Nucleares/genética , Resultado del Tratamiento , Adulto JovenRESUMEN
Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a treatment option for relapsed anaplastic large cell lymphoma (ALCL) in children, but reports on its efficacy in this disease are still limited. We analyzed data concerning 34 patients under 18 years of age prospectively registered in the French SFGM-TC database, who had undergone an allo-SCT for the treatment of ALK+ ALCL between 1993 and 2011. At transplant, 28 patients (82.4%) were in CR, whereas 6 exhibited detectable disease. Conditioning regimens were mostly myelo-ablative (n=31). With a median follow-up of 6 years, 5-year overall and event-free survival rates were 70% (SE=8%) and 58% (SE=9%), respectively. The 5-year cumulative incidence of relapse and treatment-related mortality was 18% (SE=7%) and 24% (SE=8%), respectively. Six patients had relapsed (median time, 141 days (35-235)). A durable CR had been obtained in 4/6 patients after injection of donor lymphocytes (n=1) or vinblastine-corticosteroid therapy (n=3). Ten patients had died, eight due to transplant toxicity and two due to progressive disease. Allo-SCT is an efficient treatment for pediatric patients with high-risk relapsed ALK+ ALCL. However, the overall morbidity of allo-SCT raises questions about its place, given the efficacy of targeted agents currently under development in this disease.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma Anaplásico de Células Grandes/mortalidad , Linfoma Anaplásico de Células Grandes/terapia , Proteínas Tirosina Quinasas Receptoras , Acondicionamiento Pretrasplante , Adolescente , Aloinjertos , Quinasa de Linfoma Anaplásico , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Recurrencia , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Radiofrequency ablation (RFA) has demonstrated its effectiveness in controlling metastases measuring less than 3 cm in several adult malignancies but not yet in osteosarcoma. We report our experience of RFA in the treatment of metastases in adolescents and young adults (AYA) with osteosarcoma. PROCEDURE: Sixteen patients treated for osteosarcoma in French Society of Childhood Cancer centers had undergone an RFA procedure between 2006 and 2012. RESULTS: Thirteen sessions were performed in 10 patients to treat 22 lung metastases. Seven patients were in complete remission at last follow up (range 19-51 months; median, 24 months after RFA). None had a recurrence at RFA sites. We report three cases each of hemoptysis and pneumothorax. Eight sessions were performed in seven patients to treat bone lesions. PROCEDURE was intended as: curative for a small metastatic lesion (n = 3, all in remission more than 3 years after); local control of small bone lesions in multi-metastatic diseases (n = 3); analgesia (n = 1). Complications included one first-degree burn, one fracture, and one soft tissue infection. CONCLUSIONS: RFA is feasible in AYA with osteosarcoma. It efficiently achieved local control of small peripheral lung metastases. Its role in the curative care of small secondary bone lesions remains to be confirmed.
Asunto(s)
Neoplasias Óseas , Ablación por Catéter/métodos , Neoplasias Pulmonares , Osteosarcoma , Adolescente , Adulto , Neoplasias Óseas/patología , Neoplasias Óseas/cirugía , Ablación por Catéter/efectos adversos , Niño , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/cirugía , Masculino , Metástasis de la Neoplasia , Osteosarcoma/patología , Osteosarcoma/cirugía , Estudios RetrospectivosRESUMEN
Lynch syndrome (LS) is an autosomal dominant disorder caused by a defect in one of the DNA mismatch repair genes: MLH1, MSH2, MSH6 and PMS2. In the last 15 years, an increasing number of patients have been described with biallelic mismatch repair gene mutations causing a syndrome referred to as 'constitutional mismatch repair-deficiency' (CMMR-D). The spectrum of cancers observed in this syndrome differs from that found in LS, as about half develop brain tumours, around half develop digestive tract cancers and a third develop haematological malignancies. Brain tumours and haematological malignancies are mainly diagnosed in the first decade of life, and colorectal cancer (CRC) and small bowel cancer in the second and third decades of life. Surveillance for CRC in patients with LS is very effective. Therefore, an important question is whether surveillance for the most common CMMR-D-associated cancers will also be effective. Recently, a new European consortium was established with the aim of improving care for patients with CMMR-D. At a workshop of this group held in Paris in June 2013, one of the issues addressed was the development of surveillance guidelines. In 1968, criteria were proposed by WHO that should be met prior to the implementation of screening programmes. These criteria were used to assess surveillance in CMMR-D. The evaluation showed that surveillance for CRC is the only part of the programme that largely complies with the WHO criteria. The values of all other suggested screening protocols are unknown. In particular, it is questionable whether surveillance for haematological malignancies improves the already favourable outcome for patients with these tumours. Based on the available knowledge and the discussions at the workshop, the European consortium proposed a surveillance protocol. Prospective collection of all results of the surveillance is needed to evaluate the effectiveness of the programme.
Asunto(s)
Neoplasias Encefálicas/diagnóstico , Trastornos por Deficiencias en la Reparación del ADN/genética , Neoplasias del Sistema Digestivo/diagnóstico , Neoplasias/diagnóstico , Neoplasias Encefálicas/etiología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales Hereditarias sin Poliposis/tratamiento farmacológico , Neoplasias Colorrectales Hereditarias sin Poliposis/genética , Trastornos por Deficiencias en la Reparación del ADN/complicaciones , Humanos , Leucemia/diagnóstico , Mutación , Neoplasias/etiología , Vigilancia de la PoblaciónRESUMEN
BACKGROUND: Beckwith-Wiedemann syndrome (BWS) is an overgrowth syndrome associated with an increased risk of pediatric tumors. The underlying molecular abnormalities may be genetic (CDKN1C mutations or 11p15 paternal uniparental isodisomy, pUPD) or epigenetic (imprinting center region 1, ICR1, gain of methylation, ICR1 GOM, or ICR2 loss of methylation, ICR2 LOM). AIM: We aimed to describe a cohort of 407 BWS patients with molecular defects of the 11p15 domain followed prospectively after molecular diagnosis. RESULTS: Birth weight and length were significantly higher in patients with ICR1 GOM than in the other groups. ICR2 LOM and CDKN1C mutations were associated with a higher prevalence of exomphalos. Mean adult height (regardless of molecular subtype, n = 35) was 1.8 ± 1.2 SDS, with 18 patients having a final height above +2 SDS. The prevalence of tumors was 8.6% in the whole population; 28.6 and 17.3% of the patients with ICR1 GOM (all Wilms tumors) and 11p15 pUPD, respectively, developed a tumor during infancy. Conversely, the prevalence of tumors in patients with ICR2 LOM and CDKN1C mutations were 3.1 and 8.8%, respectively, with no Wilms tumors. CONCLUSION: Based on these results for a large cohort, we formulated guidelines for the follow-up of these patients according to the molecular subtype of BWS.
Asunto(s)
Síndrome de Beckwith-Wiedemann/complicaciones , Transformación Celular Neoplásica/genética , Desarrollo Infantil , Monitoreo Fisiológico/normas , Neoplasias/etiología , Adulto , Síndrome de Beckwith-Wiedemann/epidemiología , Síndrome de Beckwith-Wiedemann/genética , Síndrome de Beckwith-Wiedemann/fisiopatología , Niño , Preescolar , Estudios de Cohortes , Femenino , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Masculino , Monitoreo Fisiológico/métodos , Neoplasias/epidemiología , Neoplasias/genética , Guías de Práctica Clínica como Asunto , Prevalencia , Factores de Riesgo , Transducción de Señal/genéticaRESUMEN
PURPOSE: Fibrolamellar hepatocellular carcinoma (FL-HCC) and conventional hepatocellular carcinoma (HCC) cases in two consecutive paediatric HCC trials were analysed to compare outcome and derive treatment implications. PATIENTS AND METHODS: Data of 24 FL-HCC (24% PRETEXT IV) and 38 HCC (42% PRETEXT IV) cases from SIOPEL-2 and -3 (1995-1998, 1998-2006) were analysed. Patients were treated according to SIOPEL-2 and -3 high-risk protocol (carboplatin+doxorubicin alternating with cisplatin; seven preoperative, three postoperative cycles) or with primary surgery followed by chemotherapy as indicated. RESULTS: Thirteen of 24 FL-HCC (54%) and 32/38 HCC (84%) were initially treated with chemotherapy. Eight FL-HCC (33%) and five HCC patients (13%) had primary surgery. Partial response was observed in 31% of FL-HCC versus 53% of HCC patients (p=0.17). Complete resection was achieved in ten FL-HCC and seven HCC patients (p=0.08). Three-year event free survival (EFS) was 22% for FL-HCC versus 28% for HCC. Overall survival (OS) was not significantly different at 3 years follow up (42% for FL-HCC versus 33% for HCC, p=0.24). EFS/OS Kaplan-Meier curves did not differ significantly, with median follow up of 43 (FL-HCC) and 60 (HCC) months. No significant correlation was found between potential prognostic factors and OS. In the entire cohort nine out of 23 (39%) patients with complete resection or orthotopic liver transplantation versus 34/39 (87%) without successful surgical treatment, died. CONCLUSIONS: Long-term OS in FL-HCC and HCC is similar. With low response rates, complete resection remains the treatment of choice.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Hígado/efectos de los fármacos , Adolescente , Carboplatino/administración & dosificación , Carcinoma Hepatocelular/cirugía , Niño , Preescolar , Cisplatino/administración & dosificación , Estudios de Cohortes , Terapia Combinada , Doxorrubicina/administración & dosificación , Femenino , Hepatectomía/métodos , Humanos , Lactante , Estimación de Kaplan-Meier , Hígado/patología , Hígado/cirugía , Neoplasias Hepáticas/cirugía , Masculino , Resultado del TratamientoRESUMEN
BACKGROUND: Mandibular osteosarcomas (MOS) mostly affect young adults. Their treatment is extrapolated from that of extragnathic osteosarcomas. MATERIAL AND METHODS: A retrospective multicooperative group study was conducted to determine the impact of chemotherapy, adjuvant radiation therapy and surgery on outcomes and to identify prognostic factors. This ethical committee-approved study included a centralized review of histology slides and operative reports. RESULTS: Of 111 patients, 58.6% were male, median age 35 years (13%, ≤18 years). Histology was osteoblastic, chondroblastic, fibroblastic, conventional not otherwise specified and others in 39.6%, 30.6%, 8.1%, 12.6% and 8.0%, respectively. Pathological World Health Organisation grades were low, intermediate and high grade in 6.4%, 11.8% and 81.8%, respectively. Surgery was carried out for 94.5% of patients. Neoadjuvant chemotherapy (mixed protocols) was carried out in 93.1% of patients. Postoperative chemotherapy and radiotherapy were carried out in 54.7% and 23.8%, respectively. Median follow-up was 59.6 months (range). Five-year local control, metastasis-free, disease-free and overall survival rates were 64.6%, 68.9%, 53.2% and 69.2%, respectively. Survival was significantly associated with age, tumor size and surgery. Wide surgery with clear margins and free flap reconstruction was the strongest prognostic factor. Neoadjuvant chemotherapy improved disease-free and metastatic-free survival and increased clear margins rates from 50% to 68%. Intermediate grades behaved like high grades in terms of metastatic-free and disease-free survival. CONCLUSION: This homogeneous series is the largest to date and emphasizes the major impact of clear margins and multidisciplinary management. Neoadjuvant chemotherapy improves disease-free survival and should be recommended for both high and intermediate grade MOS.
Asunto(s)
Manejo de la Enfermedad , Neoplasias Mandibulares/terapia , Recurrencia Local de Neoplasia/prevención & control , Osteosarcoma/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Neoplasias Mandibulares/mortalidad , Neoplasias Mandibulares/patología , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/mortalidad , Osteosarcoma/mortalidad , Osteosarcoma/secundario , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
PURPOSE: To analyse the clinical characteristics and outcome of hepatoblastoma (HB) patients who relapsed after enrolment on SIOPEL studies 1-3. PATIENTS AND METHODS: Analysis of clinical data of all 59 patients (pts) registered in SIOPEL 1-3 studies, who relapsed after achieving complete remission (CR). RESULTS: The median time from the initial diagnosis to relapse was 12 months (4-115 m). The site of relapse was lung N=27, liver N=21, both liver and lung N=5 and other N=5 (missing data-MD: 1 patient). All but 9 pts had an alpha-fetoprotein level >10 ng/mL at the time of relapse. Treatment of the relapse included chemotherapy and surgery N=25, chemotherapy alone N=21, surgery alone N=7 and only palliative treatment N=5 (MD: 1 pt). Overall, 31 pts (52%) achieved a second CR. With a median follow-up of 83 months, 23 pts are alive, (18 in 2nd CR, 5 after a second relapse) and 36 pts have died (35 from disease and 1 from complications). Three-year event-free survival and overall survival are 34% and 43% respectively (95% confidence interval [CI] 0.28-0.69). The main factors associated with a good outcome were PRETEXT group I-III at diagnosis, a high AFP level at relapse and relapse treatment including both chemotherapy and surgery. CONCLUSION: Relapses in HB are rare events occurring in less than 12% of pts after CR. Combined treatment with chemotherapy and surgical removal of the tumour is essential for long-term survival.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hepatectomía , Hepatoblastoma/mortalidad , Neoplasias Hepáticas/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Terapia Recuperativa , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Estudios de Seguimiento , Hepatoblastoma/patología , Hepatoblastoma/terapia , Humanos , Lactante , Recién Nacido , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/terapia , Masculino , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Inducción de Remisión , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
A group composed of parents, nurses, and physicians involved in pediatric cancerology has reflected on medical errors within the Espace Éthique de l'Assistance publique-Hôpitaux de Paris. Based on narratives and qualitative analysis of histories and testimonies, this discussion aimed at exploring the causes, circumstances, and impacts of medical errors on the relations between these individuals. The study demonstrated that some circumstances actually promote medical errors, such as hard working conditions, mistrust, unreliable control procedures, not listening to parents, and caring for children in extreme situations of pain and suffering. Errors almost always result from the accumulation of several shortcomings. The tensions raised by a medical error can be overcome, provided that parents and caregivers trust each other from the onset of disease and that the medical errors are disclosed in a sincere way, whatever the medical consequences. The feelings raised by the painful experience of a medical error do not solely depend on the severity of the consequences, since seemingly benign errors may lead to long-term trauma, whereas severe errors, even those leading to death, do not necessarily breach trust. The keyword here is permanent vigilance. The capacity of caregivers to question their practice, from both a technical and ethical point of view, will determine their ability to learn from an error for the future. The depth and quality of this questioning, in the best of times encouraged by the institution, may also help children affected by a medical error and their family to move forward in their personal history, beyond such painful experiences.