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Berlanga Charriel, Pablo
Font de Mora Sainz, Jaime (dir.); Cañete Nieto, Adela (dir.) Departament de Pediatria, Obstetrícia i Ginecologia |
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Aquest document és un/a tesi, creat/da en: 2017 | |
Introduction
Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Current management of high-grade osteosarcoma consists of administration of neoadjuvant/adjuvant chemotherapy and complete surgical removal of all tumour sites. The most important prognostic factors for long-term survival are: disease
extension (localized/metastatic), primary tumour location (extremity/axial), histologic response to first-line induction chemotherapy and surgical removal of all detectable lesions.
The addition of chemotherapy to surgery in the 1970s and 80s increased substantially long-term survival of osteosarcoma patients. However, no further improvement of survival has been observed since then, with currently 5-year overall survival of 60-70% for localized and 20-30% for metastatic osteosarcoma. Therefore, there is an urgent need for new therapeutic agents to im...
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Introduction
Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Current management of high-grade osteosarcoma consists of administration of neoadjuvant/adjuvant chemotherapy and complete surgical removal of all tumour sites. The most important prognostic factors for long-term survival are: disease
extension (localized/metastatic), primary tumour location (extremity/axial), histologic response to first-line induction chemotherapy and surgical removal of all detectable lesions.
The addition of chemotherapy to surgery in the 1970s and 80s increased substantially long-term survival of osteosarcoma patients. However, no further improvement of survival has been observed since then, with currently 5-year overall survival of 60-70% for localized and 20-30% for metastatic osteosarcoma. Therefore, there is an urgent need for new therapeutic agents to improve prognosis for osteosarcoma patients.
General objective:
- To identify prognostic factors, at diagnosis and relapse, for children and adolescents with high-grade osteosarcoma and identify new therapeutic targets.
Specific objectives:
- To identify prognostic factors and survival of children and adolescents with highgrade osteosarcoma at diagnosis and relapse.
- To determine the incidence and cancer distribution, treatment setting and provider
specialty of children and adolescents in the Comunidad Valenciana.
- To identify new therapeutic targets in paediatric and adolescent osteosarcoma Methods:
This PhD thesis consists of four papers of which the candidate is the first author:
1. Pablo Berlanga, Adela Cañete, Roberto Díaz, Marta Salom, Francisco Baixauli,
Jacinto Gómez, Margarita Llavador, Victoria Castel. Presentation and Long-term
Outcome of High-grade Osteosarcoma: A Single-institution Experience. J Pediatric
Hematol Oncol 2015; 37: e272-e277.
2. Pablo Berlanga, Adela Cañete, Marta Salom, Joaquin Montalar, María Guasp,
Alfredo Marco, Victoria Castel. Postrelapse Prognostic Factors in Nonmetastatic
Osteosarcoma: A Single-Institution Experience. J Pediatric Hematol Oncol 2016; 38:
176-181.
3. Pablo Berlanga, María Luisa Vicente, Adela Cañete, Carmen Alberich, Victoria
Castel. Cancer in cancer in children and adolescents in Spain: incidence, treatment
setting and provider specialty. Clin Transl Oncol 2016; 18: 27-32.
4. Pablo Berlanga, Lisandra Muñoz, Marta Piqueras, Antoni Sirerol, María Dolors
Sánchez-Izquierdo, David Hervás, Miguel Hernández, Margarita Llavador, Isidro
Machado, Antonio Llombart-Bosch, Adela Cañete, Victoria Castel, Jaime Font de
Mora. miR-200c and Akt predict osteosarcoma progression and lung metastasis.
Mol Oncol. 2016; 10: 1043-53.
This work was supported by a Predoctoral Research Fellowship from the Instituto de
Investigación Sanitaria La Fe (2011/0319)
Results and conclusions:
Five-year overall survival (OS), event-free survival (EFS) and main prognostic
factors for high-grade osteosarcoma patients in our cohort are similar to those previously described: A) At diagnosis: metastatic disease, poor histologic response to first-line induction chemotherapy and incomplete surgical removal of all detectable lesions are the main negative prognostic factors. B) At first relapse: good histologic response to neoadjuvant first-line chemotherapy and complete surgical removal of all lesions at relapse are the main favourable prognostic factors. Chemotherapy and surgery are the cornerstone of osteosarcoma treatment. Despite the important role of chemotherapy in the treatment of metastatic disease,surgical removal of all tumour lesions at first-line treatment and relapse is necessary for
long-term survival. The improvement of imaging techniques, such as the computed
tomography (TC) scan, has increased its sensitivity while decreasing its specificity in the identification of pulmonary metastases and a new definition of “pulmonary metastases” at diagnosis with current imaging techniques is needed. In order to maintain chemotherapy intensity, a delay in the resumption of chemotherapy after primary tumour surgery needs to be avoided.
Osteosarcoma incidence is higher during adolescence. Adolescents are a unique
group, with patterns of disease and healthcare challenges distinctly different than those faced by younger children and adults. In our region, childhood and adolescent cancer incidence is similar to other European countries, with higher overall incidence of malignancy in adolescents than children. Of importance, our results show an important dispersion of treatment of adolescents compared to children in the Comunidad Valenciana. We suggest the centralization of care of adolescents with cancer with the creation of specific teenager and young adult cancer centres in which these patients can benefit from the shared expertise of medical and paediatric specialists. There is an urgent need for new therapeutic agents to improve prognosis for osteosarcoma patients. PI3K/AKT/mTOR activation, determined by phopho-AKT
immunostaining, is associated with lower overall survival in osteosarcoma primary
tumours. MiR-200 is overexpressed in lung metastases and plays a role in the molecular processes of lung metastasis. Therefore, PI3k/AKT/mTOR and miR-200c inhibitors are potential therapeutic targets to prevent progression and metastasis of paediatric osteosarcomas.Introduction
Osteosarcoma is the most common primary malignant bone tumour in children and adolescents. Current management of high-grade osteosarcoma consists of administration of neoadjuvant/adjuvant chemotherapy and complete surgical removal of all tumour sites. The most important prognostic factors for long-term survival are: disease
extension (localized/metastatic), primary tumour location (extremity/axial), histologic response to first-line induction chemotherapy and surgical removal of all detectable lesions.
The addition of chemotherapy to surgery in the 1970s and 80s increased substantially long-term survival of osteosarcoma patients. However, no further improvement of survival has been observed since then, with currently 5-year overall survival of 60-70% for localized and 20-30% for metastatic osteosarcoma. Therefore, there is an urgent need for new therapeutic agents to improve prognosis for osteosarcoma patients.
General objective:
- To identify prognostic factors, at diagnosis and relapse, for children and adolescents with high-grade osteosarcoma and identify new therapeutic targets.
Specific objectives:
- To identify prognostic factors and survival of children and adolescents with highgrade osteosarcoma at diagnosis and relapse.
- To determine the incidence and cancer distribution, treatment setting and provider
specialty of children and adolescents in the Comunidad Valenciana.
- To identify new therapeutic targets in paediatric and adolescent osteosarcoma Methods:
This PhD thesis consists of four papers of which the candidate is the first author:
1. Pablo Berlanga, Adela Cañete, Roberto Díaz, Marta Salom, Francisco Baixauli,
Jacinto Gómez, Margarita Llavador, Victoria Castel. Presentation and Long-term
Outcome of High-grade Osteosarcoma: A Single-institution Experience. J Pediatric
Hematol Oncol 2015; 37: e272-e277.
2. Pablo Berlanga, Adela Cañete, Marta Salom, Joaquin Montalar, María Guasp,
Alfredo Marco, Victoria Castel. Postrelapse Prognostic Factors in Nonmetastatic
Osteosarcoma: A Single-Institution Experience. J Pediatric Hematol Oncol 2016; 38:
176-181.
3. Pablo Berlanga, María Luisa Vicente, Adela Cañete, Carmen Alberich, Victoria
Castel. Cancer in cancer in children and adolescents in Spain: incidence, treatment
setting and provider specialty. Clin Transl Oncol 2016; 18: 27-32.
4. Pablo Berlanga, Lisandra Muñoz, Marta Piqueras, Antoni Sirerol, María Dolors
Sánchez-Izquierdo, David Hervás, Miguel Hernández, Margarita Llavador, Isidro
Machado, Antonio Llombart-Bosch, Adela Cañete, Victoria Castel, Jaime Font de
Mora. miR-200c and Akt predict osteosarcoma progression and lung metastasis.
Mol Oncol. 2016; 10: 1043-53.
This work was supported by a Predoctoral Research Fellowship from the Instituto de
Investigación Sanitaria La Fe (2011/0319)
Results and conclusions:
Five-year overall survival (OS), event-free survival (EFS) and main prognostic
factors for high-grade osteosarcoma patients in our cohort are similar to those previously described: A) At diagnosis: metastatic disease, poor histologic response to first-line induction chemotherapy and incomplete surgical removal of all detectable lesions are the main negative prognostic factors. B) At first relapse: good histologic response to neoadjuvant first-line chemotherapy and complete surgical removal of all lesions at relapse are the main favourable prognostic factors. Chemotherapy and surgery are the cornerstone of osteosarcoma treatment. Despite the important role of chemotherapy in the treatment of metastatic disease,surgical removal of all tumour lesions at first-line treatment and relapse is necessary for
long-term survival. The improvement of imaging techniques, such as the computed
tomography (TC) scan, has increased its sensitivity while decreasing its specificity in the identification of pulmonary metastases and a new definition of “pulmonary metastases” at diagnosis with current imaging techniques is needed. In order to maintain chemotherapy intensity, a delay in the resumption of chemotherapy after primary tumour surgery needs to be avoided.
Osteosarcoma incidence is higher during adolescence. Adolescents are a unique
group, with patterns of disease and healthcare challenges distinctly different than those faced by younger children and adults. In our region, childhood and adolescent cancer incidence is similar to other European countries, with higher overall incidence of malignancy in adolescents than children. Of importance, our results show an important dispersion of treatment of adolescents compared to children in the Comunidad Valenciana. We suggest the centralization of care of adolescents with cancer with the creation of specific teenager and young adult cancer centres in which these patients can benefit from the shared expertise of medical and paediatric specialists. There is an urgent need for new therapeutic agents to improve prognosis for osteosarcoma patients. PI3K/AKT/mTOR activation, determined by phopho-AKT
immunostaining, is associated with lower overall survival in osteosarcoma primary
tumours. MiR-200 is overexpressed in lung metastases and plays a role in the molecular processes of lung metastasis. Therefore, PI3k/AKT/mTOR and miR-200c inhibitors are potential therapeutic targets to prevent progression and metastasis of paediatric osteosarcomas.
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