High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patient... more High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and m...
With improvements in the survival rates after childhood cancer, many clinicians have turned their... more With improvements in the survival rates after childhood cancer, many clinicians have turned their attention to reporting on late effects, and how they might be prevented or treated. In childhood the thyroid gland is especially vulnerable to the carcinogenic action of ionizing radiation. This retrospective study focused on secondary thyroid cancers seen at our institution over more than 30 years (between 1980 and 2012) in patients treated for other malignancies in pediatric age. 36 patients were identified. In most cases, the primary cancer had been Hodgkin disease, and all the patients had been administered radiotherapy for their first malignancy. The secondary thyroid cancers were treated with total thyroidectomy in 27 cases (six with lymphadenectomy), and hemithyroidectomy in nine (one with lymphadenectomy). 12 Patients were also given radiometabolic therapy. All but two had TSH suppression therapy. The histological diagnoses were: 31 papillary and five follicular carcinomas. At 5 and 10 years, the OS was 100 and 95 %, respectively, and the PFS was 96 and 83 %. None of the patients died of their thyroid disease. Nodal involvement at onset was the only factor correlating with recurrence. Surgical sequelae only occurred in patients who underwent total thyroidectomy. Survival in these patients did not depend on the extent of surgery on the thyroid parenchyma. Our data confirm a good prognosis for secondary thyroid cancer, prompting us to encourage a minimalist approach to the treatment of these particular patients wherever possible.
The treatment applied in our Institution to children with localized osteosarcoma between 1991 and... more The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 10(6) IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.
The treatment applied in our Institution to children with localized osteosarcoma between 1991 and... more The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 10(6) IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.
Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing th... more Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing the presence of metastatic cells in bone marrow (BM) and peripheral blood (PB) obtained from rhabdomysarcoma (RMS) patients. Myogenin (Myf4), a specific molecular RMS marker, was also investigated in the same samples. Since neuroblastoma (NB) metastasizes to the BM, the potential application of cytometry in differential diagnosis was explored. Patients and Methods: CD45, CD56, CD90 and CD57 antibodies were used in 7 paired BM and PB samples (from 7 RMS stage IV patients at presentation), 23 BM samples (from 13 RMS stage I and II patients at presentation), and ten paired BM and PB samples taken at presentation and five BM samples taken at recurrence from 13 NB stage 4 patients. Results: All seven BM samples from RMS stage IV (but not those from patients with localized disease) showed both the CD45-CD56+ phenotype and the Myf4 transcript. Four cases also showed CD90 and two CD57 positivity. Neither the CD45-CD56+ phenotype, nor Myf4 were recorded in the BM and PB samples from patients with localized disease. All the NB BM samples (15/15) showed the CD45-CD56+ CD90+ phenotype and 10/15 also showed CD57 positivity. Only 3/10 blood samples from the NB patients revealed tumor cells. Conclusion: CD45, CD56, CD90 and CD57 antibodies can be used in FCM for marrow metastasis detection in both, RMS and NB patients.
Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing th... more Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing the presence of metastatic cells in bone marrow (BM) and peripheral blood (PB) obtained from rhabdomysarcoma (RMS) patients. Myogenin (Myf4), a specific molecular RMS marker, was also investigated in the same samples. Since neuroblastoma (NB) metastasizes to the BM, the potential application of cytometry in differential diagnosis was explored. Patients and Methods: CD45, CD56, CD90 and CD57 antibodies were used in 7 paired BM and PB samples (from 7 RMS stage IV patients at presentation), 23 BM samples (from 13 RMS stage I and II patients at presentation), and ten paired BM and PB samples taken at presentation and five BM samples taken at recurrence from 13 NB stage 4 patients. Results: All seven BM samples from RMS stage IV (but not those from patients with localized disease) showed both the CD45-CD56+ phenotype and the Myf4 transcript. Four cases also showed CD90 and two CD57 positivity. Neither the CD45-CD56+ phenotype, nor Myf4 were recorded in the BM and PB samples from patients with localized disease. All the NB BM samples (15/15) showed the CD45-CD56+ CD90+ phenotype and 10/15 also showed CD57 positivity. Only 3/10 blood samples from the NB patients revealed tumor cells. Conclusion: CD45, CD56, CD90 and CD57 antibodies can be used in FCM for marrow metastasis detection in both, RMS and NB patients.
The potential impact of diagnostic delays on patients&amp... more The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools. To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS. Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, nonrhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61). Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
The potential impact of diagnostic delays on patients&amp... more The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools. To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS. Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, nonrhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61). Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages w... more Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages w... more Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ew... more To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma. The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0. A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients' median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectiv...
To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ew... more To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma. The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0. A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients' median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectiv...
We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying se... more We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying serum and CSF anti-Hu antibodies that were able to recognize antigens of the patient's own tumor.
We describe the case of a woman cured of osteosarcoma who took part in a mono-institutional study... more We describe the case of a woman cured of osteosarcoma who took part in a mono-institutional study using different questionnaires to assess pediatric cancer survivors' quality of life and behavioral features 12 years after completing her cancer treatment. The high levels of psychological distress and psychopathologic symptoms revealed by this patient prompted us to offer her specific and prolonged support at our institution, since she refused to seek the help of other psychiatric services. The woman revealed a dysfunctional social and family setting and a borderline personality disorder. She was hospitalized after attempting suicide. No psychological distress had previously come to light during her long follow-up for cancer. Cancer survivors are at risk of psychological and behavioral problems, so they should be followed up over time. Questionnaires and standard scales are important, but not enough: the physician-patient relationship is crucial to bring out a patient's psychological issues and needs. This means that dedicated resources should be made available, whenever possible.
High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patient... more High-dose chemotherapy with haemopoietic stem-cell rescue improves event-free survival in patients with high-risk neuroblastoma; however, which regimen has the greatest patient benefit has not been established. We aimed to assess event-free survival after high-dose chemotherapy with busulfan and melphalan compared with carboplatin, etoposide, and melphalan. We did an international, randomised, multi-arm, open-label, phase 3 cooperative group clinical trial of patients with high-risk neuroblastoma at 128 institutions in 18 countries that included an open-label randomised arm in which high-dose chemotherapy regimens were compared. Patients (age 1-20 years) with neuroblastoma were eligible to be randomly assigned if they had completed a multidrug induction regimen (cisplatin, carboplatin, cyclophosphamide, vincristine, and etoposide with or without topotecan, vincristine, and doxorubicin) and achieved an adequate disease response. Patients were randomly assigned (1:1) to busulfan and m...
With improvements in the survival rates after childhood cancer, many clinicians have turned their... more With improvements in the survival rates after childhood cancer, many clinicians have turned their attention to reporting on late effects, and how they might be prevented or treated. In childhood the thyroid gland is especially vulnerable to the carcinogenic action of ionizing radiation. This retrospective study focused on secondary thyroid cancers seen at our institution over more than 30 years (between 1980 and 2012) in patients treated for other malignancies in pediatric age. 36 patients were identified. In most cases, the primary cancer had been Hodgkin disease, and all the patients had been administered radiotherapy for their first malignancy. The secondary thyroid cancers were treated with total thyroidectomy in 27 cases (six with lymphadenectomy), and hemithyroidectomy in nine (one with lymphadenectomy). 12 Patients were also given radiometabolic therapy. All but two had TSH suppression therapy. The histological diagnoses were: 31 papillary and five follicular carcinomas. At 5 and 10 years, the OS was 100 and 95 %, respectively, and the PFS was 96 and 83 %. None of the patients died of their thyroid disease. Nodal involvement at onset was the only factor correlating with recurrence. Surgical sequelae only occurred in patients who underwent total thyroidectomy. Survival in these patients did not depend on the extent of surgery on the thyroid parenchyma. Our data confirm a good prognosis for secondary thyroid cancer, prompting us to encourage a minimalist approach to the treatment of these particular patients wherever possible.
The treatment applied in our Institution to children with localized osteosarcoma between 1991 and... more The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 10(6) IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.
The treatment applied in our Institution to children with localized osteosarcoma between 1991 and... more The treatment applied in our Institution to children with localized osteosarcoma between 1991 and 1999 consisted of four interleukin 2 (IL-2) courses (9 x 10(6) IU/mL/daily x 4), alternated with pre- and post-operative polichemotherapy. The aims of the present study were to quantify the modifications of some immunological parameters induced by IL-2 and to verify whether polychemotherapy could reduce them. An additional aim was to assess whether any correlation between the immune modifications and the clinical outcome could be found. We evaluated in 18 consecutive patients the following changes, induced in blood by each IL-2 course: number of lymphocyte subpopulations and natural killer (NK) cells, lymphokine activated killer (LAK) and NK activities. Chemotherapy did not influence the modifications of the number of NK and CD4+ cells and of the LAK and NK activities, induced by each of the four courses of IL-2. The magnitudo of the NK activity and the peak of the NK absolute counts significantly correlated with the clinical outcome. The results show that the use of IL-2 permitted a repeated immune activation despite the intensive chemotherapy. Furthermore, although the limited number of cases precludes any definitive conclusion, the results suggest a possible role of the NK cells in the control of osteosarcoma.
Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing th... more Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing the presence of metastatic cells in bone marrow (BM) and peripheral blood (PB) obtained from rhabdomysarcoma (RMS) patients. Myogenin (Myf4), a specific molecular RMS marker, was also investigated in the same samples. Since neuroblastoma (NB) metastasizes to the BM, the potential application of cytometry in differential diagnosis was explored. Patients and Methods: CD45, CD56, CD90 and CD57 antibodies were used in 7 paired BM and PB samples (from 7 RMS stage IV patients at presentation), 23 BM samples (from 13 RMS stage I and II patients at presentation), and ten paired BM and PB samples taken at presentation and five BM samples taken at recurrence from 13 NB stage 4 patients. Results: All seven BM samples from RMS stage IV (but not those from patients with localized disease) showed both the CD45-CD56+ phenotype and the Myf4 transcript. Four cases also showed CD90 and two CD57 positivity. Neither the CD45-CD56+ phenotype, nor Myf4 were recorded in the BM and PB samples from patients with localized disease. All the NB BM samples (15/15) showed the CD45-CD56+ CD90+ phenotype and 10/15 also showed CD57 positivity. Only 3/10 blood samples from the NB patients revealed tumor cells. Conclusion: CD45, CD56, CD90 and CD57 antibodies can be used in FCM for marrow metastasis detection in both, RMS and NB patients.
Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing th... more Background: The goal of this study was to develop a flow cytometric (FCM) method for assessing the presence of metastatic cells in bone marrow (BM) and peripheral blood (PB) obtained from rhabdomysarcoma (RMS) patients. Myogenin (Myf4), a specific molecular RMS marker, was also investigated in the same samples. Since neuroblastoma (NB) metastasizes to the BM, the potential application of cytometry in differential diagnosis was explored. Patients and Methods: CD45, CD56, CD90 and CD57 antibodies were used in 7 paired BM and PB samples (from 7 RMS stage IV patients at presentation), 23 BM samples (from 13 RMS stage I and II patients at presentation), and ten paired BM and PB samples taken at presentation and five BM samples taken at recurrence from 13 NB stage 4 patients. Results: All seven BM samples from RMS stage IV (but not those from patients with localized disease) showed both the CD45-CD56+ phenotype and the Myf4 transcript. Four cases also showed CD90 and two CD57 positivity. Neither the CD45-CD56+ phenotype, nor Myf4 were recorded in the BM and PB samples from patients with localized disease. All the NB BM samples (15/15) showed the CD45-CD56+ CD90+ phenotype and 10/15 also showed CD57 positivity. Only 3/10 blood samples from the NB patients revealed tumor cells. Conclusion: CD45, CD56, CD90 and CD57 antibodies can be used in FCM for marrow metastasis detection in both, RMS and NB patients.
The potential impact of diagnostic delays on patients&amp... more The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools. To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS. Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, nonrhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61). Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
The potential impact of diagnostic delays on patients&amp... more The potential impact of diagnostic delays on patients' outcomes is a debated issue in pediatric oncology and discordant results have been published so far. We attempted to tackle this issue by analyzing a prospective series of 351 consecutive children and adolescents with solid malignancies using innovative statistical tools. To address the nonlinear complexity of the association between symptom interval and overall survival (OS), a regression tree algorithm was constructed with sequential binary splitting rules and used to identify homogeneous patient groups vis-à-vis functional relationship between diagnostic delay and OS. Three different groups were identified: group A, with localized disease and good prognosis (5-year OS 85.4%); group B, with locally or regionally advanced, or metastatic disease and intermediate prognosis (5-year OS 72.9%), including neuroblastoma, Wilms tumor, nonrhabdomyosarcoma soft tissue sarcoma, and germ cell tumor; and group C, with locally or regionally advanced, or metastatic disease and poor prognosis (5-year OS 45%), including brain tumors, rhabdomyosarcoma, and bone sarcoma. The functional relationship between symptom interval and mortality risk differed between the three subgroups, there being no association in group A (hazard ratio [HR]: 0.96), a positive linear association in group B (HR: 1.48), and a negative linear association in group C (HR: 0.61). Our analysis suggests that at least a subset of patients can benefit from an earlier diagnosis in terms of survival. For others, intrinsic aggressiveness may mask the potential effect of diagnostic delays. Based on these findings, early diagnosis should remain a goal for pediatric cancer patients.
Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages w... more Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages w... more Forty-three fresh tumor specimens of human neuroblastoma belonging to different clinical stages were analyzed for the expression of 2 proto-oncogenes: trk, which encodes a tyrosine-kinase receptor for nerve growth factor (NGF) and ret, another receptor-type tyrosine kinase whose ligand is unknown. The mRNA expression of the trk gene was detected in 67.4% of cases, with increased frequency in I, II and IVs Evans' stages and in patients with favorable prognosis according to the Shimada classification. Moreover, trk expression inversely correlated with Nmyc-gene amplification. ret mRNA was found in 36.8% of cases and equally distributed in the different stages. In addition, ngfR (low-affinity NGF receptor)-gene expression was present in 9 out of 25 cases. The simultaneous presence of mRNA related to both forms of the NGF receptor, while not proving the presence of a functional receptor, indicates the existence of a sub-set of neuroblastoma cells potentially responsive to NGF.
To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ew... more To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma. The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0. A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients' median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectiv...
To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ew... more To assess the efficacy and toxicity of low-dose oral etoposide (VP) 16 in relapsing/refractory Ewing sarcoma. The records of all patients treated at our department between 1989 and 2012 for relapsing/refractory Ewing sarcoma who received oral VP-16 were analyzed. The dose was 40 mg/m2 daily for 21 consecutive days in every 28. Response was assessed after 2/3 cycles according to Response Evaluation Criteria in Solid Tumors 1.0. A total of 46 of 58 patients completed at least 2 cycles; 12 suspended the treatment earlier due to rapid disease progression. The patients' median age at diagnosis was 14 years and 25/58 had metastatic disease. All patients received intensive polychemotherapy including VP-16 IV as first- (n = 53) or second-line (n = 5) treatment; 21/58 had myeloablative regimens with peripheral blood stem cell rescue, and 1 underwent allogeneic stem cell transplantation. Oral VP-16 was prescribed as 2nd-, 3rd-, and 4th-line treatment for 19, 27, and 12 patients, respectiv...
We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying se... more We describe a case of a patient with neuroblastoma and opsoclonus- myoclonus ataxia displaying serum and CSF anti-Hu antibodies that were able to recognize antigens of the patient's own tumor.
We describe the case of a woman cured of osteosarcoma who took part in a mono-institutional study... more We describe the case of a woman cured of osteosarcoma who took part in a mono-institutional study using different questionnaires to assess pediatric cancer survivors' quality of life and behavioral features 12 years after completing her cancer treatment. The high levels of psychological distress and psychopathologic symptoms revealed by this patient prompted us to offer her specific and prolonged support at our institution, since she refused to seek the help of other psychiatric services. The woman revealed a dysfunctional social and family setting and a borderline personality disorder. She was hospitalized after attempting suicide. No psychological distress had previously come to light during her long follow-up for cancer. Cancer survivors are at risk of psychological and behavioral problems, so they should be followed up over time. Questionnaires and standard scales are important, but not enough: the physician-patient relationship is crucial to bring out a patient's psychological issues and needs. This means that dedicated resources should be made available, whenever possible.
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Papers by Roberto Luksch