Pancras C . W . Hogendoorn
Leiden University, Pathology, Faculty Member
- Professor of Pathology and Dean of the Leiden University Medical Center Doctor Honoris Causa Semmelweis University, ... moreProfessor of Pathology and Dean of the Leiden University Medical Center
Doctor Honoris Causa Semmelweis University, Budapest, Hungary
Visiting Professor at University of Oxford and Free University Brussels
Member of the European and Royal Netherlands Academy of Arts and Sciences
https://orcid.org/0000-0002-1513-8104edit
Aims The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with... more
Aims
The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands.
Methods and results
We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist-assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations.
Conclusions
This population-based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers.
The discovery of somatic genetic alterations established many histiocytic disorders as haematologic neoplasms. We aimed to investigate the demographic characteristics and additional haematologic cancers of patients diagnosed with histiocytic disorders in The Netherlands.
Methods and results
We retrieved data on histiocytosis patients from the Dutch Nationwide Pathology Databank (Palga). During 1993 to 2022, more than 4000 patients with a pathologist-assigned diagnosis of a histiocytic disorder were registered in Palga. Xanthogranulomas were the most common subtype, challenging the prevailing assumption that Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder. LCH and juvenile xanthogranuloma (JXG) had a peak incidence in the first years of life; males were overrepresented among all histiocytosis subgroups. 118 patients had a histiocytic disorder and an additional haematologic malignancy, including 107 (91%) adults at the time of histiocytosis diagnosis. In 16/118 patients, both entities had been analysed for the same genetic alteration(s). In 11 of these 16 patients, identical genetic alterations had been detected in both haematologic neoplasms. This included two patients with PAX5 p.P80R mutated B cell acute lymphoblastic leukaemia and secondary histiocytic sarcoma, further supporting that PAX5 alterations may predispose (precursor) B cells to differentiate into the myeloid lineage. All 4/11 patients with myeloid neoplasms as their additional haematologic malignancy had shared N/KRAS mutations.
Conclusions
This population-based study highlights the frequency of xanthogranulomas. Furthermore, our data add to the growing evidence supporting clonal relationships between histiocytic/dendritic cell neoplasms and additional myeloid or lymphoid malignancies. Particularly adult histiocytosis patients should be carefully evaluated for the development of these associated haematologic cancers.
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The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate... more
The phase III clinical study of adjuvant liposomal muramyl tripeptide (MTP-PE) in resected high-grade osteosarcoma (OS) documented positive results that have been translated into regulatory approval, supporting initial promise for innate immune therapies in OS. There remains, however, no new approved treatment such as MTP-PE for either metastatic or recurrent OS. Whilst the addition of different agents, including liposomal MTP-PE, to surgery for metastatic or recurrent high-grade osteosarcoma has tried to improve response rates, a mechanistic hiatus exists in terms of a detailed understanding the therapeutic strategies required in advanced disease. Here we report a Bayesian designed multi-arm, multi-centre, open-label phase II study with randomisation in patients with metastatic and/or recurrent OS, designed to investigate how patients with OS might respond to liposomal MTP-PE, either given alone or in combination with ifosfamide. Despite the trial closing because of poor recruitment within the allocated funding period, with no objective responses in eight patients, we report the design and feasibility outcomes for patients registered into the trial. We demonstrate the feasibility of the Bayesian design, European collaboration, tissue collection with genomic analysis and serum cytokine characterisation. Further mechanistic investigation of liposomal MTP-PE alone and in combination with other agents remains warranted in metastatic OS.
10037 Background: Brostallicin (B) is a DNA minor groove binder which showed activity in a recent phase II study in patients with soft tissue sarcoma (STS) failing first line therapy (Leahy et al, Eur J Cancer 2007;43:308-15). The present... more
10037 Background: Brostallicin (B) is a DNA minor groove binder which showed activity in a recent phase II study in patients with soft tissue sarcoma (STS) failing first line therapy (Leahy et al, Eur J Cancer 2007;43:308-15). The present study assessed the safety and efficacy of first line B compared to doxorubicin (D) in patients with advanced or metastatic STS older than 60 or not fit enough to receive combination chemotherapy. Methods: Patients (pts) with progressive advanced (metastatic or locally advanced and inoperable) intermediate to high grade STS were randomized in a 2:1 ratio between IV B 10mg/m2 and D 75 mg/m2 once every 3 weeks for a maximum of 6 cycles. The primary endpoint was documented disease stabilization (RECIST) at 26 weeks, and 35+/72 successes were required to consider results as positive. Results: 118 pts were included (B 79 pts and D 39 pts). Median age was 66 years (range 27-88), male/female ratio 50/50, WHO 0/1 ratio 51/49. Primary tumour or recurrence was present in 39% of pat...
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Gadolinium-enhanced magnetic resonance (MR) images were correlated with histopathologic findings in patients with cartilaginous tumors. Short repetition time/echo time spin-echo MR images obtained before and after intravenous... more
Gadolinium-enhanced magnetic resonance (MR) images were correlated with histopathologic findings in patients with cartilaginous tumors. Short repetition time/echo time spin-echo MR images obtained before and after intravenous administration of gadopentetate dimeglumine in 34 patients were evaluated. Twenty-four of 27 low-grade chondrosarcomas showed septal enhancement. The enhancing curvilinear speta consisted of fibrovascular tissue. The nonehancing areas consisted of paucicellular hyaline cartilage, cystic mucoid tissue, and necrosis. This enhancement pattern and corresponding histopathologic findings were not seen in three benign osteochondromas or four high-grade chondrosarcomas. Inhomogeneous or homogeneous enhancement correlating with highly cellular areas at histopathologic analysis was seen in all high-grade chondrosarcomas. The three osteochondromas showed peripheral enhancement that correlated with fibrovascular tissue covering the non-enhancing cartilage cap. The authors conclude that septal enhancement on MR images after intravenous administration of gadopentetate dimeglumine improves tissue characterization of cartilaginous tumors and may assist in identifying low-grade chondrosarcoma.
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1. Lancet. 1990 Feb 24;335(8687):481. Searching publication data bases. Schoones JW. Comment in Lancet. 1990 Apr 14;335(8694):917. Comment on Lancet. 1990 Jan 6;335(8680):20-1. PMID: 1968206 [PubMed - indexed for MEDLINE]. Publication... more
1. Lancet. 1990 Feb 24;335(8687):481. Searching publication data bases. Schoones JW. Comment in Lancet. 1990 Apr 14;335(8694):917. Comment on Lancet. 1990 Jan 6;335(8680):20-1. PMID: 1968206 [PubMed - indexed for MEDLINE]. Publication Types: Comment; Letter; Meta-Analysis. MeSH Terms. MEDLARS; Meta-Analysis as Topic; Online Systems*; Publishing*; United States.
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The c-kit oncogene, encoding for a transmembrane growth-factor receptor with tyrosine-kinase activity (KIT), plays an important role in the tumourigenesis of gastrointestinal stroma-cell tumours (GISTs). GISTs are a heterogeneous group of... more
The c-kit oncogene, encoding for a transmembrane growth-factor receptor with tyrosine-kinase activity (KIT), plays an important role in the tumourigenesis of gastrointestinal stroma-cell tumours (GISTs). GISTs are a heterogeneous group of mesenchymal tumours, mainly localised in the abdomen. Immunohistochemical staining using antibodies directed towards the c-kit protein on the cell surface, is a useful tool in the often difficult differential diagnosis of GISTs from other mesenchymal tumours. The correct diagnosis of GISTs is crucial for the new treatment option with imatinib, the tyrosine-kinase inhibitor specifically targeted against KIT. The clinical development of imatinib for patients with GISTs has been extraordinarily rapid. As a result of the short period of time between the drug's experimental introduction and actual registration, many unanswered questions about its use for the treatment of GISTs remain. These can only be answered in well-designed clinical trials. It i...
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Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns surrounded by fibrous cells. Evidence as to whether this neoplasm should be designated as an... more
Adamantinoma of long bones is a rare malignant tumor composed of cells with epithelial characteristics in various differentiation patterns surrounded by fibrous cells. Evidence as to whether this neoplasm should be designated as an epithelial bone tumor or a biphasic sarcoma with both epithelial and mesenchymal features is lacking. In this study the nature of the mesenchymal and epithelial components of adamantinoma was investigated by DNA flow cytometry, DNA image cytometry, p53 immunohistochemistry, and polymerase chain reaction-based loss of heterozygosity detection at the p53 locus. Specimens from 6 of 15 patients (40%) analyzed by flow cytometry had an aneuploid DNA index. Image cytometry analysis of Feulgen-stained paraffin sections of 6 aneuploid and 2 diploid tumors revealed that aneuploid nuclei were detected in cells with an epithelial phenotype only, whereas all fibrous cells were diploid. Immunohistochemistry for p53 on specimens from 25 patients revealed moderate or str...
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The pathogenesis of pulmonary leukostasis in leukemia was studied in a rat model by investigating the course of its development. Leukemia was induced by inoculating rats with leukemic cells. The earliest stage of leukostasis was found... more
The pathogenesis of pulmonary leukostasis in leukemia was studied in a rat model by investigating the course of its development. Leukemia was induced by inoculating rats with leukemic cells. The earliest stage of leukostasis was found from day 14 onward, when leukemic cells appeared in the peripheral blood, and was characterized by accumulation of leukemic cells at the capillary level. Simultaneous with the increase of leukemic cell concentrations in the peripheral blood, accumulation in capillaries increased gradually over a period of several days. This was accompanied by increasing severity of tachypnea. Shortly before death, aggregates consisting almost solely of leukemic cells were found in medium-sized blood vessels. This stage was rapidly followed by the end-stage, characterized by complete obstruction of the lung vasculature--including the largest arteries and veins--by leukemic cell aggregates, giving rise to extensive hemorrhages and edema. The end-stage was considered to b...
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The interaction between nephritogenic antibodies and antigens in the glomerular capillary wall is influenced by physicochemical determinants such as the electrical charge. We studied the effect of neutralization of a negative glomerular... more
The interaction between nephritogenic antibodies and antigens in the glomerular capillary wall is influenced by physicochemical determinants such as the electrical charge. We studied the effect of neutralization of a negative glomerular capillary wall (GCW) charge by polyethyleneimine (PEI) on the binding of anti-renal tubular epithelium (RTE) IgG in passive Heymann nephritis. For these studies, glomerular binding of intravenously administered radiolabeled anti-RTE IgG was determined in Wistar rats preinjected 30 minutes earlier with either 0.2 ml 0.05% PEI (molecular weight 40,000 kd) or 0.2 ml saline solution; control rats received 0.025 mg radiolabeled nonimmune rabbit IgG (NRIgG) after PEl or saline solution. Glomerulus-bound antibody was measured in saline solution-perfused isolated glomeruli 1 hour after this injection. Intravenously administered radiolabeled anti-RTE IgG binding was found to be significantly increased in rats pretreated with PEI compared with those given sali...
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Two men aged 17 and 23 years had a swelling on the foot which was neither an abscess nor a ganglion. Histological study revealed Ewing's sarcoma and synoviosarcoma, respectively. In both patients amputation under the knee was... more
Two men aged 17 and 23 years had a swelling on the foot which was neither an abscess nor a ganglion. Histological study revealed Ewing's sarcoma and synoviosarcoma, respectively. In both patients amputation under the knee was performed; nevertheless both developed metastases. In case of a swelling of the foot the possibility of malignancy has to be considered in order to shorten the diagnostic period. Consultation of the 'Commissie voor Beentumoren' may be desirable because of the low incidence and often difficult diagnostic process.
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It is sometimes difficult to make an unequivocal diagnosis of tumours of bone and soft tissue based upon classical morphology alone, which has led to an increased use of additional diagnostic tools. In the past decade new techniques have... more
It is sometimes difficult to make an unequivocal diagnosis of tumours of bone and soft tissue based upon classical morphology alone, which has led to an increased use of additional diagnostic tools. In the past decade new techniques have become available, based on tumour specific genetic alterations, for instance chromosomal translocations. With the cloning of the translocation breakpoints and the identification of the genes involved, the reverse transcriptase polymerase chain reaction (RT-PCR) detection of the fusion gene has become an important diagnostic test. Also, non-tumour specific genetic alterations with prognostic value can be detected.
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ABSTRACT
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Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is... more
Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is the subject of conflicting discussions and the potential link has implications for the diagnosis, prognosis, and treatment. Clinical aspects of adamantinomas are described: location, age, gender, symptoms, imaging, diagnosis, treatment, clinical course, prognosis. Histopathology is extensively covered for usual and peculiar forms. Immunohistochemical results are described and discussed. Data of electron microscopy, cytological findings, and DNA flow cytometry are also reported. The putative association with osteofibrous dysplasia is the subject of an extensive development with the report of the personal experience and works of the authors, and arguments for viewing osteofibrous dysplasia and "osteofibrous dysplasia-like" adamantinomas as ...
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Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response... more
Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP). Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be </= 65 years of age. Treatment consisted of doxorubicin 25 mg/m(2)/d days 1 through 3 and cisplatin 100 mg/m(2) by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. Forty-one patients had operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 1...
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To prospectively evaluate color Doppler flow imaging (CDFI) with spectral analysis versus dynamic gadolinium-enhanced magnetic resonance (MR) imaging and three-phase bone scintigraphy in monitoring the effect of chemotherapy on bone... more
To prospectively evaluate color Doppler flow imaging (CDFI) with spectral analysis versus dynamic gadolinium-enhanced magnetic resonance (MR) imaging and three-phase bone scintigraphy in monitoring the effect of chemotherapy on bone sarcomas. Seventeen osteosarcomas and five Ewing sarcomas were examined with these imaging techniques before and after chemotherapy. Results were compared with the histopathologic response. Before chemotherapy, high systolic Doppler frequency shifts (DFSs) and/or low-impedance Doppler signals were found in all but one tumor. Resistive indexes (RIs) in tumor-feeding arteries were substantially lower than in contralateral normal arteries. After chemotherapy, DFSs disappeared in five of seven good respondents and remained substantial in all but one poor respondent. RIs increased substantially in all good respondents and decreased or showed minor changes only in all but one poor respondent. CDFI with spectral analysis has an advantage over the other two tech...
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Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the... more
Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l). Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation.
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Purpose Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased... more
Purpose Single-agent doxorubicin remains the standard treatment for advanced soft tissue sarcomas. Combining doxorubicin with standard-dose ifosfamide has not been shown to improve survival and is associated with a significantly increased toxicity; it is not known whether higher dose single-agent ifosfamide is superior to doxorubicin. Patients and Methods This randomized prospective multicenter phase III trial was designed to compare progression-free survival of patients with advanced soft tissue sarcoma receiving either regimen of standard doxorubicin 75 mg/m2 every 21 days, ifosfamide 9 g/m2 over 3 days continuous infusion, or ifosfamide 3 g/m2 per day in 3 hours over 3 days. The primary end point was progression-free survival. Secondary end points included overall survival, response rate, and toxicity. Results The study included 326 patients. Grade 4 leukopenia, neutropenia, febrile neutropenia, and encephalopathy were more frequent in the ifosfamide arms. Progression-free surviv...
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Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL High-grade osteosarcoma is a tumor with a complex genomic profile, occurring primarily in adolescents. The extensive genomic alterations obscure the... more
Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL High-grade osteosarcoma is a tumor with a complex genomic profile, occurring primarily in adolescents. The extensive genomic alterations obscure the identification of genes driving tumorigenesis in osteosarcoma progenitor cells. In order to identify such driver genes, we integrated DNA copy number profiles (Affymetrix SNP 6.0) of 32 diagnostic biopsies with 84 expression profiles (Illumina Human-6 v2.0) of osteosarcoma as compared with its putative progenitor cells, i.e. mesenchymal stem cells (n=12) or osteoblasts (n=3). In addition, we performed paired analyses between copy number and expression profiles of a subset of 29 patients for which we had both DNA and mRNA profiles. Integrative analyses were performed in Nexus Copy Number Software and statistical language R. Paired analyses were performed on all probes which were significantly differentially expressed in corresponding LIMMA analyses. For both non-paired and paired analyses, copy number aberration frequency was set to >35%. Non-paired integrative analyses resulted in 45 genes that were present in both analyses using different control sets, i.e. MSCs and osteoblasts. 101 genes overlapped between the two paired integrative analyses. Paired analyses detected >90% of all genes found with the corresponding non-paired analyses. Remarkably, approximately twice as many genes as found in the corresponding non-paired analyses were detected. Affected genes were compared with differential expression in osteosarcoma cell lines. An overrepresentation of altered cell division related genes was found, such as MCM4 and LATS2, suggesting that deregulation of the cell cycle is an initial driver of osteosarcomagenesis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5128. doi:1538-7445.AM2012-5128
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Introduction: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be... more
Introduction: Giant cell tumour of bone (GCTB) is an expansile osteolytic tumour of bone which contains numerous osteoclast-like giant cells. GCTB is a locally aggressive tumour which can cause extensive bone destruction that can be difficult to control surgically, up to 35% of cases recurring after simple curettage. Bisphosphonates are anti-resorptive agents that have proved effective in the treatment of a number of osteolytic conditions. Methods: This study reports results from four European centres where bisphosphonates are being used to treat problematic GCTBs. Details of treatment with bisphosphonates of 25 cases of primary, recurrent and metastatic GCTBs was assessed clinically and radiologically. Results: Most primary/recurrent tumours did not exhibit progressive enlargement and, in some cases, both primary and metastatic GCTBs showed a degree of radiological improvement following treatment. Some patients also noted relief of pain following treatment. In a few cases, no apparent treatment effect was noted and there was disease progression. Several inoperable large spinal/pelvic GCTBs remained stable in size following treatment. Discussion: Our findings provide preliminary evidence for the use of bisphosphonates to inhibit the progressive osteolysis associated with GCTB. These agents had a beneficial clinical and/or radiological effect in most cases. This study reports results from four European centres and highlights the fact that these centres are all employing different clinical indications and different regimes of bisphosphonate treatment. Bisphosphonates have significant side effects and indications for treatment and standardisation of drug type and dosage regimes (and measurement of agreed outcome measures to determine treatment efficacy) should be established for the use of these agents to control GCTB tumour growth and osteolysis.
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ABSTRACT
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Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the... more
Enchondromatosis is characterized by the presence of multiple benign cartilage lesions in bone. While Ollier disease is typified by multiple enchondromas, in Maffucci syndrome these are associated with hemangiomas. Studies evaluating the predictive value of clinical symptoms for development of secondary chondrosarcoma and prognosis are lacking. This multi-institute study evaluates the clinical characteristics of patients, to get better insight on behavior and prognosis of these diseases. A retrospective study was conducted using clinical data of 144 Ollier and 17 Maffucci patients from 13 European centers and one national databank supplied by members of the European Musculoskeletal Oncology Society. Patients had multiple enchondromas in the hands and feet only (group I, 18%), in long bones including scapula and pelvis only (group II, 39%), and in both small and long/flat bones (group III, 43%), respectively. The overall incidence of chondrosarcoma thus far is 40%. In group I, only 4 patients (15%) developed chondrosarcoma, in contrast to 27 patients (43%) in group II and 26 patients (46%) in group III, respectively. The risk of developing chondrosarcoma is increased when enchondromas are located in the pelvis (odds ratio, 3.8; p = 0.00l). Overall incidence of development of chondrosarcoma is 40%, but may, due to age-dependency, increase when considered as a lifelong risk. Patients with enchondromas located in long bones or axial skeleton, especially the pelvis, have a seriously increased risk of developing chondrosarcoma, and are identified as the population that needs regular screening on early detection of malignant transformation.
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Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is... more
Adamantinoma of long bones is a perplexing tumor for its histology as well as for its histogenesis. Recent progress has been made with ultrastructural and immunohistochemical works. The possible relationship with osteofibrous dysplasia is the subject of conflicting discussions and the potential link has implications for the diagnosis, prognosis, and treatment. Clinical aspects of adamantinomas are described: location, age, gender, symptoms, imaging, diagnosis, treatment, clinical course, prognosis. Histopathology is extensively covered for usual and peculiar forms. Immunohistochemical results are described and discussed. Data of electron microscopy, cytological findings, and DNA flow cytometry are also reported. The putative association with osteofibrous dysplasia is the subject of an extensive development with the report of the personal experience and works of the authors, and arguments for viewing osteofibrous dysplasia and &quot;osteofibrous dysplasia-like&quot; adamantinomas as precursor lesions of classic adamantinomas are favoured.
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Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response... more
Studies involving small case series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival. In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP). Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be &lt;/= 65 years of age. Treatment consisted of doxorubicin 25 mg/m(2)/d days 1 through 3 and cisplatin 100 mg/m(2) by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. Forty-one patients had operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 16 (42%) of 38 assessable specimens showed a good pathologic response (&gt;/= 90% necrosis). Median time to progression was 56 months, and the 5-year progression-free survival rate was 56% (95% confidence interval [CI], 40% to 72%). Median survival time was 63 months, and the 5-year survival rate was 59% (95% CI, 41% to 77%). Patients with a good pathologic response had longer survival times and times to progression than did those with a poor response. Also treated were two patients with locally recurrent and nine with metastatic disease, and these patients had a median survival time of 17.5 months. Our study suggests that adjuvant or neoadjuvant chemotherapy with DOX/DDP is beneficial in MFH-B. Good pathologic response rates and survivals are quite comparable with those for osteosarcoma, a related bone tumor for which adjuvant or neoadjuvant chemotherapy is an accepted practice.
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Research Interests: Magnetic Resonance Imaging, Immunohistochemistry, Adolescent, Medicine, Literature Review, and 15 moreHumans, Female, Male, Magnetic Resonance, Differential Diagnosis, Contrast-Enhanced Ultrasound, Clinical Sciences, Aged, Middle Aged, Malignant Melanoma, Adult, Retrospective Studies, Musculoskeletal system, Soft Tissue, and Mr Imaging
To prospectively evaluate color Doppler flow imaging (CDFI) with spectral analysis versus dynamic gadolinium-enhanced magnetic resonance (MR) imaging and three-phase bone scintigraphy in monitoring the effect of chemotherapy on bone... more
To prospectively evaluate color Doppler flow imaging (CDFI) with spectral analysis versus dynamic gadolinium-enhanced magnetic resonance (MR) imaging and three-phase bone scintigraphy in monitoring the effect of chemotherapy on bone sarcomas. Seventeen osteosarcomas and five Ewing sarcomas were examined with these imaging techniques before and after chemotherapy. Results were compared with the histopathologic response. Before chemotherapy, high systolic Doppler frequency shifts (DFSs) and/or low-impedance Doppler signals were found in all but one tumor. Resistive indexes (RIs) in tumor-feeding arteries were substantially lower than in contralateral normal arteries. After chemotherapy, DFSs disappeared in five of seven good respondents and remained substantial in all but one poor respondent. RIs increased substantially in all good respondents and decreased or showed minor changes only in all but one poor respondent. CDFI with spectral analysis has an advantage over the other two techniques in monitoring the efficacy of chemotherapy in bone sarcomas because of its superior accuracy, noninvasive nature, availability, and low cost.
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The purpose of this study was to use color Doppler flow imaging to predict the response to preoperative chemotherapy in patients with Ewing&#39;s sarcoma or high-grade osteosarcomas early in treatment. Color Doppler flow imaging was... more
The purpose of this study was to use color Doppler flow imaging to predict the response to preoperative chemotherapy in patients with Ewing&#39;s sarcoma or high-grade osteosarcomas early in treatment. Color Doppler flow imaging was done in 31 patients before, during, and after chemotherapy. In each phase of treatment, semiquantitative changes in intratumoral blood flow, changes in maximum intratumoral Doppler shifts, and changes in resistive indexes of arteries feeding limbs that contained tumors relative to contralateral normal arteries were compared with the histopathologic response, as evaluated on the resected specimens. Before chemotherapy, pathologic flow was found in the extraosseous component of all but two patients. Resistive indexes in arteries that fed tumors were significantly lower (p &lt; .001) than the resistive indexes in the contralateral normal arteries. Histopathologic response could not be predicted on the basis of the initial measurements of Doppler shifts and resistive indexes taken before or after the first cycle of chemotherapy. Histopathologic response could be predicted after the second cycle of chemotherapy. After the second cycle of chemotherapy, the resistive index in the arteries that fed tumors increased in eight of nine good respondents but did not change or decreased in eight of nine poor respondents (p = .03). Lower intratumoral Doppler shifts were measured in six of 10 good respondents but also in five of 13 poor respondents (p = .07). After the full course of chemotherapy, persistent lower resistive indexes were measured in the arteries that fed tumors in all poor respondents but one. Intratumoral flow and Doppler shifts further decreased in all good respondents but one. Changes in Doppler shifts (p = .001) and resistive indexes (p &lt; .001) were statistically significant between good and poor respondents, irrespective of the tumor type studied. Decreased or unaltered resistive index in the arteries that feed tumors in addition to persistent intratumoral flow and high-frequency Doppler shifts after two cycles of chemotherapy suggest poor histologic response to chemotherapy in osteosarcoma and Ewing&#39;s sarcoma. An increased resistive index after two cycles is indicative of good response.
Research Interests: Adolescent, Medicine, Humans, Child, Female, and 6 moreOsteosarcoma, Male, American, Clinical Sciences, Adult, and Ewing sarcoma
10525 Background: The EORTC STBSG has coordinated the two largest trials of adCT vs no adCT in localized high grade STS. In both studies adCT failed to demonstrate any benefit on overall survival (OS). The aim of this analysis was to... more
10525 Background: The EORTC STBSG has coordinated the two largest trials of adCT vs no adCT in localized high grade STS. In both studies adCT failed to demonstrate any benefit on overall survival (OS). The aim of this analysis was to identify subgroups of patients who benefit more from adjuvant CT than others. Methods: We pooled individual patient (pt) data from two EORTC trials comparing adCT (CYVADIC in 62771 and AI in 62931) to a control arm in completely resected STS (R0 or R1) to identify prognostic factors, by univariate and a multivariate analysis. The outcome of pts (OS or PFS) was subsequently compared between the two groups of pts according to each investigated factor. Results: A total of 819 pts were included, with a median follow-up of 8.2 years (62771 trial: 468 pts, 9.7 yrs; 62931 trial: 351 pts; 6.6 yrs). Large tumor size, high histologic grade and R1 resection are independent adverse prognostic factors for both PFS and OS. AdCT is an independent favourable prognostic factor for PFS but not...
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Results Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having... more
Results Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were ...
Research Interests: Publishing, Nonparametric Statistics, Evidence Based Medicine, Treatment Outcome, Medicine, and 15 moreEngland, Humans, United States, Bibliographic Databases, Publication Bias, Information Storage and Retrieval, New England, Review Literature As Topic, Drug Industry, New England Journalof Medicine, Government Regulation, Clinical Trials as Topic, Treatment Failure, Medical and Health Sciences, and Antidepressive agents
Ten-Year Progression-Free and Overall Survival in Patients With Unresectable or Metastatic GI Stromal Tumors: Long-Term Analysis of the European Organisation for Research and Treatment of Cancer, Italian Sarcoma Group, and Australasian Gastrointestinal Trials Group Intergroup Phase III Randomized...more
Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and... more
Purpose To report on the long-term results of a randomized trial comparing a standard dose (400 mg/d) versus a higher dose (800 mg/d) of imatinib in patients with metastatic or locally advanced GI stromal tumors (GISTs). Patients and Methods Eligible patients with advanced CD117-positive GIST from 56 institutions in 13 countries were randomly assigned to receive either imatinib 400 mg or 800 mg daily. Patients on the 400-mg arm were allowed to cross over to 800 mg upon progression. Results Between February 2001 and February 2002, 946 patients were accrued. Median age was 60 years (range, 18 to 91 years). Median follow-up time was 10.9 years. Median progression-free survival times were 1.7 and 2.0 years in the 400- and 800-mg arms, respectively (hazard ratio, 0.91; P = .18), and median overall survival time was 3.9 years in both treatment arms. The estimated 10-year progression-free survival rates were 9.5% and 9.2% for the 400- and 800-mg arms, respectively, and the estimated 10-yea...
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ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European... more
ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific tumour type. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Colorectal cancer: essential requirements for quality care CONCLUSION: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality CRC service. The ECCO expert group is aware that it is not possible to propose a 'one size fits all' system for all countries, but urges that access t...
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The presence of a t(11;22)(q24;q12) translocation is one of the characteristic features of the Ewing family of tumors. The detection of the fusion gene product by RT-PCR using primers at both sides of the breakpoints has been advocated as... more
The presence of a t(11;22)(q24;q12) translocation is one of the characteristic features of the Ewing family of tumors. The detection of the fusion gene product by RT-PCR using primers at both sides of the breakpoints has been advocated as a diagnostic tool. By applying this technique appropriate internal controls are required. We found that the use of normal non-rearranged EWS mRNA as an internal control for RNA quality may lead to conflicting data. We obtained PCR products of the expected size for the normal EWS mRNA in both RNA and DNA samples, suggesting, the existence of one or more EWS pseudogenes. A 109 bp sequence at the 5&#39; end of this PCR-product contained a correctly spliced exon junction and was 97% homologous to the EWS cDNA sequence. Similarly two such junctions were found in a 346 bp sequence of the 3&#39; end, which was 89% homologous. Hence EWS should not be used as an internal control for the RNA quality in a RT-PCR based test for the presence of the translocation.