Cost-effectiveness of the McGill interactive pediatric oncogenetic guidelines in identifying Li-Fraumeni syndrome in female patients with osteosarcoma.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a penetrant cancer predisposition syndrome (CPS) associated with the development of many tumor types in young people including osteosarcoma and breast cancer (BC). The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) decision-support tool provides a standardized approach to identify patients at risk of CPSs. METHODS: We conducted a cost-utility analysis, from the healthcare payer perspective, to compare MIPOGG-guided, physician-guided, and universal genetic testing strategies to detect LFS in female patients diagnosed at an age of less than 18 years with osteosarcoma. We developed a decision tree and discrete-event simulation model to simulate the clinical and cost outcomes of the three genetic referral strategies on a cohort of female children diagnosed with osteosarcoma, especially focused on BC as subsequent cancer. Outcomes included BC incidence, quality-adjusted life-years (QALYs), healthcare costs, and incremental cost-utility ratios (ICURs). We conducted probabilistic and scenario analyses to assess the uncertainty surrounding model parameters. RESULTS: Compared to the physician-guided testing, the MIPOGG-guided strategy was marginally more expensive by $105 (-$516; $743), but slightly more effective by 0.003 (-0.04; 0.045) QALYs. Compared to MIPOGG, the universal testing strategy was $1333 ($732; $1953) more costly and associated with 0.011 (-0.043; 0.064) additional QALYs. The ICUR for the MIPOGG strategy was $33,947/QALY when compared to the physician strategy; the ICUR for universal testing strategy was $118,631/QALY when compared to the MIPOGG strategy. DISCUSSION: This study provides evidence for clinical and policy decision-making on the cost-effectiveness of genetic referral strategies to identify LFS in the setting of osteosarcoma. MIPOGG-guided strategy was most likely to be cost-effective at a willingness-to-pay threshold value of $50,000/QALY.

Assessment of the Interval to Diagnosis in Pediatric Bone Sarcoma.

OBJECTIVES: The timely diagnosis of primary bone malignancies in pediatric patients is critical to clinical outcomes. The purpose of this study is to investigate the initial presentation of pediatric bone sarcoma patients to an academic health care system and assess the current interval to diagnosis. METHODS: We conducted a retrospective review of pediatric patients (aged 1-18) with biopsy-proven diagnosis of osteosarcoma or Ewing sarcoma presenting between 2004 and 2020. All living patients had 1 year or more of follow-up. Primary outcomes were interval to diagnosis, clinical features on initial presentation, percent of patients with negative radiographic workup at initial presentation, and number of health care encounters before diagnosis. RESULTS: Seventy-one patients (osteosarcoma, 51; Ewing sarcoma, 20) were included. Average age at presentation was 13.1 ± 3.3 years (range, 4.4-18.3). Average symptom duration was 5.4 ± 13.9 months (range, 0.1-84). Clinical features at initial presentation included limb/back pain (91.5% of patients), activity modification/pain medication use (78.9%), palpable mass (40.8%), night pain (35.2%), limp (25.4%), limb disuse (18.3%), and recent fever history (2.8%). Fourteen of 71 patients (19.7%) had negative radiographs at initial presentation. Average number of health care encounters before diagnosis was 1.9 ± 0.6 (range, 1.0-4.0), with most in the outpatient pediatrician clinics (81.2%) and emergency department (18.3%). Average time to diagnosis from initial presentation was 19.5 ± 65 days (range, 0-493); the 14 patients with initial negative radiographs had a statistically significant prolonged interval to diagnosis of 54 ± 134 days (range, 0-493; P = 0.018). CONCLUSIONS: We found pediatric patients with primary bone sarcoma present with an average interval to diagnosis of 20 days. Twenty percent of patients had a significantly prolonged interval to diagnosis of 54 days. Clinical features suggest night pain is not a sensitive indicator. In patients of appropriate age with persistent unilateral pain in suspicious locations, early advanced imaging with magnetic resonance imaging should be considered.

Expression of immune-related genes as prognostic biomarkers for the assessment of osteosarcoma clinical outcomes.

Cancer immunotherapy is a promising therapeutic approach, but the prognostic value of immune-related genes in osteosarcoma (OS) is unknown. Here, Target-OS RNA-seq data were analyzed to detect differentially expressed genes (DEGs) between OS subgroups, followed by functional enrichment analysis. Cox proportional risk regression was performed for each immune-related gene, and a risk score model to predict the prognosis of patients with OS was constructed. The risk scores were calculated using the risk signature to divide the training set into high-risk and low-risk groups, and validation was performed with GSE21257. We identified two immune-associated clusters, C1 and C2. C1 was closely related to immunity, and the immune score was significantly higher in C1 than in C2. Furthermore, we validated 6 immune cell hub genes related to the prognosis of OS: CD8A, KIR2DL1, CD79A, APBB1IP, GAL, and PLD3. Survival analysis revealed that the prognosis of the high-risk group was significantly worse than that of the low-risk group. We also explored whether the 6-gene prognostic risk model was effective for survival prediction. In conclusion, the constructed a risk score model based on immune-related genes and the survival of patients with OS could be a potential tool for targeted therapy.

Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas.

BACKGROUND: While racial/ethnic survival disparities have been described in pediatric oncology, the impact of income has not been extensively explored. We analyzed how public insurance influences 5-year overall survival (OS) in young patients with sarcomas. METHODS: The University of California San Francisco Cancer Registry was used to identify patients aged 0-39 diagnosed with bone or soft tissue sarcomas between 2000 and 2015. Low-income patients were defined as those with no insurance or Medicaid, a means-tested form of public insurance. Survival curves were computed using the Kaplan-Meier method and compared using log-rank tests and Cox models. Causal mediation was used to assess whether the association between public insurance and mortality is mediated by metastatic disease. RESULTS: Of 1106 patients, 39% patients were classified as low-income. Low-income patients were more likely to be racial/ethnic minorities and to present with metastatic disease (OR 1.96, 95% CI 1.35-2.86). Low-income patients had significantly worse OS (61% vs 71%). Age at diagnosis and extent of disease at diagnosis were also independent predictors of OS. When stratified by extent of disease, low-income patients consistently had significantly worse OS (localized: 78% vs 84%, regional: 64% vs 73%, metastatic: 23% vs 30%, respectively). Mediation analysis indicated that metastatic disease at diagnosis mediated 15% of the effect of public insurance on OS. CONCLUSIONS: Low-income patients with bone and soft tissue sarcomas had decreased OS regardless of disease stage at presentation. The mechanism by which insurance status impacts survival requires additional investigation, but may be through reduced access to care.

Psychosocial Distress in Follow-up Care - Results of a Tablet-based Routine Screening in 202 Patients With Sarcoma.

BACKGROUND: Patients with sarcoma are particularly vulnerable to psychosocial distress. The aim of this study was to collect preliminary data on the prevalence of psychosocial distress in such patients during follow-up care and identify risk factors associated with higher psycho-oncological stress levels. PATIENTS AND METHODS: The study retrospectively enrolled 202 patients with bone or soft-tissue sarcomas who underwent routine psychosocial distress screening during their follow-up care. All patients were screened using an electronic cancer-specific questionnaire. RESULTS: Females and patients who underwent radiotherapy were more distressed. Psychosocial distress levels were markedly higher in the early postoperative phase, but approximately one-third of patients showed high psychosocial distress levels even more than 2 years postoperatively. CONCLUSION: The results underscore the importance of routine psychosocial distress screenings in patients with sarcoma, which should be performed throughout the follow-up period.

Viable and necrotic tumor assessment from whole slide images of osteosarcoma using machine-learning and deep-learning models.

Pathological estimation of tumor necrosis after chemotherapy is essential for patients with osteosarcoma. This study reports the first fully automated tool to assess viable and necrotic tumor in osteosarcoma, employing advances in histopathology digitization and automated learning. We selected 40 digitized whole slide images representing the heterogeneity of osteosarcoma and chemotherapy response. With the goal of labeling the diverse regions of the digitized tissue into viable tumor, necrotic tumor, and non-tumor, we trained 13 machine-learning models and selected the top performing one (a Support Vector Machine) based on reported accuracy. We also developed a deep-learning architecture and trained it on the same data set. We computed the receiver-operator characteristic for discrimination of non-tumor from tumor followed by conditional discrimination of necrotic from viable tumor and found our models performing exceptionally well. We then used the trained models to identify regions of interest on image-tiles generated from test whole slide images. The classification output is visualized as a tumor-prediction map, displaying the extent of viable and necrotic tumor in the slide image. Thus, we lay the foundation for a complete tumor assessment pipeline from original histology images to tumor-prediction map generation. The proposed pipeline can also be adopted for other types of tumor.

Comparative Assessment of the Accuracy of Cytological and Histologic Biopsies in the Diagnosis of Canine Bone Lesions.

BACKGROUND: Osteosarcoma (OSA) should be differentiated from other less frequent primary bone neoplasms, metastatic disease, and tumor-like lesions, as treatment and prognosis can vary accordingly. Hence, a preoperative histologic diagnosis is generally preferred. This requires collection of multiple biopsies under general anesthesia, with possible complications, including pathological fractures. Fine-needle aspiration cytology would allow an earlier diagnosis with a significant reduction of discomfort and morbidity. HYPOTHESIS/OBJECTIVES: The aim of this study was to compare the accuracy of cytological and histologic biopsies in the diagnosis of canine osteodestructive lesions. ANIMALS: Sixty-eight dogs with bone lesions. METHODS: Retrospective study. Accuracy was assessed by comparing the former diagnosis with the final histologic diagnosis on surgical or post-mortem samples or, in the case of non-neoplastic lesions, with follow-up information. RESULTS: The study included 50 primary malignant bone tumors (40 OSAs, 5 chondrosarcomas, 2 fibrosarcomas, and 3 poorly differentiated sarcomas), 6 carcinoma metastases, and 12 non-neoplastic lesions. Accuracy was 83% for cytology (sensitivity, 83.3%; specificity, 80%) and 82.1% for histology (sensitivity, 72.2%; specificity, 100%). Tumor type was correctly identified cytologically and histologically in 50 and 55.5% of cases, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: The accuracy of cytology was similar to histology, even in the determination of tumor type. In no case was a benign lesion diagnosed as malignant on cytology. This is the most important error to prevent, as treatment for malignant bone tumors includes aggressive surgery. Being a reliable diagnostic method, cytology should be further considered to aid decisions in the preoperative setting of canine bone lesions.

Unplanned Resection of Sarcoma.

Unplanned resection is a common problem in the management of sarcoma. Because sarcomas are so rare, they may be misdiagnosed initially as more common benign lesions. When the treating surgeon is unaware of or does not adhere to proper surgical principles of orthopaedic oncology, an intralesional procedure may be performed without the requisite preoperative imaging, staging, or wide resection margins for optimal management of sarcoma. Studies show that oncologic outcomes after unplanned resections are mixed; however, surgical outcomes drastically deteriorate. Failure to adhere to oncologic principles accounts for increased morbidity and amputation rates with re-resection. No diagnostic modality has been proven to accurately predict residual disease in the resection bed following unplanned resection. Thus, repeat surgery with or without adjuvant treatment is usually offered to these patients, thereby adding considerable cost and morbidity. Medical malpractice litigation associated with unplanned sarcoma resection is common, with delayed diagnosis and unnecessary amputation most often cited in cases decided in favor of the plaintiff.

Performance of Positron Emission Tomography and Positron Emission Tomography/Computed Tomography Using Fluorine-18-Fluorodeoxyglucose for the Diagnosis, Staging, and Recurrence Assessment of Bone Sarcoma: A Systematic Review and Meta-Analysis.

To investigate the performance of fluorine-18-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) and PET/computed tomography (CT) in the diagnosis, staging, restaging, and recurrence surveillance of bone sarcoma by systematically reviewing and meta-analyzing the published literature.To retrieve eligible studies, we searched the MEDLINE, Embase, and the Cochrane Central library databases using combinations of following Keywords: "positron emission tomography" or "PET," and "bone tumor" or "bone sarcoma" or "sarcoma." Bibliographies from relevant articles were also screened manually. Data were extracted and the pooled sensitivity, specificity, and diagnostic odds ratio (DOR), on an examination-based or lesion-based level, were calculated to appraise the diagnostic accuracy of F-FDG PET and PET/CT. All statistical analyses were performed using Meta-Disc 1.4.Forty-two trials were eligible. The pooled sensitivity and specificity of PET/CT to differentiate primary bone sarcomas from benign lesions were 96% (95% confidence interval [CI], 93-98) and 79% (95% CI, 63-90), respectively. For detecting recurrence, the pooled results on an examination-based level were sensitivity 92% (95% CI, 85-97), specificity 93% (95% CI, 88-96), positive likelihood ratio (PLR) 10.26 (95% CI, 5.99-17.60), and negative likelihood ratio (NLR) 0.11 (95% CI, 0.05-0.22). For detecting distant metastasis, the pooled results on a lesion-based level were sensitivity 90% (95% CI, 86-93), specificity 85% (95% CI, 81-87), PLR 5.16 (95% CI, 2.37-11.25), and NLR 0.15 (95% CI, 0.11-0.20). The accuracies of PET/CT for detecting local recurrence, lung metastasis, and bone metastasis were satisfactory. Pooled outcome estimates of F-FDG PET were less complete compared with those of PET/CT.F-FDG PET and PET/CT showed a high sensitivity for diagnosing primary bone sarcoma. Moreover, PET/CT demonstrated excellent accuracy for the staging, restaging, and recurrence surveillance of bone sarcoma. However, to avoid misdiagnosis, pathological examination or long-term follow-up should be carried out for F-FDG-avid lesions in patients with suspected bone sarcoma.

Diagnostic assessment of osteosarcoma chemoresistance based on Virtual Clinical Trials.

Osteosarcoma is the most common primary bone tumor in pediatric and young adult patients. Successful treatment of osteosarcomas requires a combination of surgical resection and systemic chemotherapy, both neoadjuvant (prior to surgery) and adjuvant (after surgery). The degree of necrosis following neoadjuvant chemotherapy correlates with the subsequent probability of disease-free survival. Tumors with less than 10% of viable cells after treatment represent patients with a more favorable prognosis. However, being able to predict early, such as at the time of the pre-treatment tumor biopsy, how the patient will respond to the standard chemotherapy would provide an opportunity for more personalized patient care. Patients with unfavorable predictions could be studied in a protocol, rather than a standard setting, towards improving therapeutic success. The onset of necrotic cells in osteosarcomas treated with chemotherapeutic agents is a measure of tumor sensitivity to the drugs. We hypothesize that the remaining viable cells, i.e., cells that have not responded to the treatment, are chemoresistant, and that the pathological characteristics of these chemoresistant tumor cells within the osteosarcoma pre-treatment biopsy can predict tumor response to the standard-of-care chemotherapeutic treatment. This hypothesis can be tested by comparing patient histopathology samples before, as well as after treatment to identify both morphological and immunochemical cellular features that are characteristic of chemoresistant cells, i.e., cells that survived treatment. Consequently, using computational simulations of dynamic changes in tumor pathology under the simulated standard of care chemotherapeutic treatment, one can couple the pre- and post-treatment morphological and spatial patterns of chemoresistant cells, and correlate them with patient clinical diagnoses. This procedure, that we named 'Virtual Clinical Trials', can serve as a potential predictive biomarker providing a novel value-added decision support tool for oncologists.

A novel assessment method of serum alkaline phosphatase for the diagnosis of osteosarcoma in children and adolescents.

BACKGROUND: A high serum alkaline phosphatase (ALP) level is valuable for the diagnosis of osteosarcoma in adults, but its use in teenagers is problematic because ALP levels are affected by age, gender, and pubertal stage. Because serum acid phosphatase (ACP) shows the same tetraphasic pattern as serum ALP in children and adolescents, we presumed that serum levels of ALP and ACP would have a strong correlation and that the ratio of ALP to ACP (ALP/ACP) would show little variation and would be useful for the diagnosis of osteosarcoma in teenagers. The purpose of this study was to evaluate the correlation between the serum levels of ALP and ACP and to investigate the validity of ALP/ACP in the differential diagnosis of osteosarcoma in children and adolescents. METHODS: We retrospectively examined 538 patients aged 1-18 years, including 24 with osteosarcomas, 8 with other malignant bone tumors, 56 with benign bone tumors, and with 450 non-tumor lesions (controls). We evaluated the serum levels of ALP and ACP, both obtained by preoperative examination. RESULTS: There were significant correlations between the serum ALP and ACP levels in the controls (r = 0.805 in males and r = 0.860 in females). The ratios of ALP to ACP in the controls showed little variation with age. In ROC curve analysis, to discriminate between the osteosarcomas and the controls, the cutoff levels of serum ALP and ALP/ACP were 956 (U/l) and 50.9 in males and 748 (U/l) and 43.3 in females, respectively. The sensitivity and specificity of serum ALP and ALP/ACP in the differential diagnosis of osteosarcoma were 50.0 and 89.0%, and 60.0 and 94.1%, respectively in males, and 61.5 and 72.7%, and 69.2 and 84.2%, respectively, in females. CONCLUSIONS: The results suggest that ALP/ACP is more useful than the serum ALP level in diagnosing osteosarcoma because it is little affected by the age.

Role of dynamic MRI and clinical assessment in predicting histologic response to neoadjuvant chemotherapy in bone sarcomas.

BACKGROUND: Neoadjuvant chemotherapy has become the first-line therapy in management of malignant bone tumors. Response to it is best assessed with evaluation of tumor necrosis postoperatively. This study was carried out to evaluate the role of clinical parameters and dynamic magnetic resonance imaging (MRI) to predict the histologic response before surgery. MATERIALS AND METHODS: Our study included 14 patients (12 osteosarcoma and 2 malignant fibrous histiocytoma) with mean age of 21.8 years, treated with neoadjuvant chemotherapy followed by surgery, who were evaluated clinically and with dynamic MRI twice, before starting chemotherapy and before surgery. Clinical parameters (pain, tumor girth, maximum tumor diameter, surface temperature, and consistency) and dynamic MRI parameter (slope of signal intensity-time curve) were correlated with histologic response (percentage of necrosis) using Pearson and Spearman correlation test. RESULTS: Significant correlation with histologic necrosis was seen in change in pain, tumor girth, maximum tumor diameter, surface temperature, and dynamic MRI slope (P<0.01). Change in consistency did not show significant correlation (P>0.05). Complete relieve of pain with reduction of >4 grades, ≥5% reduction in tumor girth, ≥8% reduction in tumor diameter, attainment of normal body temperature or decrease of ≥2°F temperature, and ≥60% reduction in slope proved to be an indicator of good histologic response. CONCLUSIONS: Both dynamic MRI and clinical evaluation are reliable methods of assessment of response of the bone tumors to neoadjuvant chemotherapy.

Quantitative assessment of the association of COX-2 (Cyclooxygenase-2) immunoexpression with prognosis in human osteosarcoma: a meta-analysis.

BACKGROUND: Numerous studies examining the relationship between Cyclooxygenase-2 (COX-2) immunoexpression and clinical outcome in osteosarcoma patients have yielded inconclusive results. METHODS: We accordingly conducted a meta-analysis of 9 studies (442 patients) that evaluated the correlation between COX-2 immunoexpression and clinical prognosis (death). Pooled odds ratios (OR) and risk ratios (RR) with 95% confidence intervals (95% CI) were calculated using the random-effects or fixed-effects model. RESULTS: Meta-analysis showed no significant association between COX-2 positivity and age, gender, tumor location, histology, stage, metastasis or 90% necrosis. Conversely, COX-2 immunoexpression was associated with overall survival rate (RR=2.12; 95% CI: 1.10-3.74; P=0.009) and disease-free survival rate (RR=1.63; 95% CI: 1.17-2.28; P=0.004) at 2 years. Sensitivity analysis performed by omitting low quality studies showed that the pooled results were stable. CONCLUSIONS: COX-2 positivity was associated with a lower 2-year overall survival rate and disease-free survival rate. COX-2 expression change is an independent prognostic factor in patients with osteosarcoma.

Sociooccupational and physical outcomes more than 20 years after the diagnosis of osteosarcoma in children and adolescents: limb salvage versus amputation.

BACKGROUND: To the best of the authors' knowledge, there has been relatively little research published to date regarding very long-term survivors of childhood and adolescent osteosarcoma. In the current study, the authors compared the very long-term survival outcomes of patients with osteosarcoma who were treated with either limb salvage procedures or amputation. METHODS: A total of 38 patients with osteosarcoma who survived ≥ 20 years from the time of diagnosis were divided into 2 groups according to whether they underwent amputation or limb salvage. Participants were asked to complete a questionnaire concerning their education, employment, annual income, marital status, health insurance, lifestyle, siblings, and all current and past health issues. RESULTS: Education, employment, marital status, and health insurance were not found to differ significantly between the 2 groups of survivors, who described themselves as being similar to their siblings. Eight percent of survivors underwent secondary amputation because of complications with an endoprosthesis. The cumulative incidence of second primary neoplasms was 13%, and this finding was significantly higher in females and in survivors who underwent radiotherapy and had a genetic predisposition. The second primary malignancies were breast cancer (ductal invasive carcinoma, ductal in situ carcinoma, and leiomyosarcoma), mediastinal leiomyosarcoma, and squamocellular carcinoma of the oral cavity and the uterine cervix. Amputees required more assistive walking support than survivors who received limb salvage treatment (P<.05, chi-square test). CONCLUSIONS: Despite the many challenges that osteosarcoma survivors face, patients who survived ≥ 20 years after their initial diagnosis reported having overall adjusted well to their physical limitations and were productive individuals.

Malignant fibrous histiocytoma and fibrosarcoma of bone: a re-assessment in the light of currently employed morphological, immunohistochemical and molecular approaches.

Malignant fibrous histiocytoma (MFH) and fibrosarcoma (FS) of bone are rare malignant tumours and contentious entities. Sixty seven cases labelled as bone MFH (57) and bone FS (10) were retrieved from five bone tumour referral centres and reviewed to determine whether recent advances allowed for reclassification and identification of histological subgroups with distinct clinical behaviour. A panel of immunostains was applied: smooth muscle actin, desmin, h-caldesmon, cytokeratin AE1-AE3, CD31, CD34, CD68, CD163, CD45, S100 and epithelial membrane antigen. Additional fluorescence in situ hybridisation and immunohistochemistry were performed whenever appropriate. All cases were reviewed by six bone and soft tissue pathologists and a consensus was reached. Follow-up for 43 patients (median 42 months, range 6-223 months) was available. Initial histological diagnosis was reformulated in 18 cases (26.8 %). Seven cases were reclassified as leiomyosarcoma, six as osteosarcoma, three as myxofibrosarcoma and one each as embryonal rhabdomyosarcoma and interdigitating dendritic cell sarcoma. One case showed a peculiar biphasic phenotype with epithelioid nests and myofibroblastic spindle cells. Among the remaining 48 cases, which met the WHO criteria for bone FS and bone MFH, we identified five subgroups. Seven cases were reclassified as undifferentiated pleomorphic sarcoma (UPS) and 11 as UPS with incomplete myogenic differentiation due to positivity for at least one myogenic marker. Six were reclassified as spindle cell sarcoma not otherwise specified. Among the remaining 24 cases, we identified a further two recurrent morphologic patterns: eight cases demonstrated a myoepithelioma-like phenotype and 16 cases a myofibroblastic phenotype. One of the myoepithelioma-like cases harboured a EWSR1-NFATC2 fusion. It appears that bone MFH and bone FS represent at best exclusion diagnoses.

Imaging assessment of osteosarcoma in childhood and adolescence: diagnosis, staging, and evaluating response to chemotherapy.

Osteosarcoma is an aggressive tumor of mesenchymal origin, capable of producing osteoid and immature bone. It is the most frequent primary malignant skeletal neoplasm in children and adolescents. Imaging studies play a major role in initial diagnosis, staging, and assessment of tumor response to chemotherapy. Conventional radiography is the prime imaging modality for diagnosis of bony tumors. Radionuclide bone scan is used in detection of metastatic lesions in the other bones. Computed tomography may be used as an adjunct to conventional radiography, but its main role is detection of pulmonary metastasis. The standard magnetic resonance imaging is the most specific modality for local staging and monitoring response to chemotherapy, and distinguishing postsurgical changes from residual tumor. Dynamic contrast-enhanced magnetic resonance imaging has been introduced to quantify the percentage of tumor necrosis, identify early responders, and thus predict survival. The role of 18F fluorodeoxyglucose positron emission tomography (PET) in the staging and management of osteosarcoma is evolving. It has the advantage of total body imaging and may have an overall role in tumor staging and grading, detection of early response, and therefore, in the prognosis and detection of recurrence.

[The role of clinical and imaging criteria in risk assessment during preoperative chemotherapy for osteosarcoma].

Prognosis for stage IIB osteosarcoma was evaluated versus the role of preoperative management of clinico-radiologic status in 293 patients. Three--five preoperative intra-arterial cycles of doxorubicin 90mg/m2 or cisplatin 120mg/m2 were given in 1986-1999, and later were followed by 3-4 cycles of doxorubicin and cisplatin in similar doses. Clinico-radiologic status was assessed in the course of preoperative chemotherapy. One hundred fifty patients were alive at the last examination, 139 had died of tumor progression, and 4 - chemotherapy complication. The two courses of preoperative chemotherapy were followed by more favorable outcome. Complete clinical response, tumors downsized to 300 mm, intra-osseous healing, periosteal assimilation and margination of extra-osseous masses had a significant positive impact on disease-free survival in the chemotherapy group. The data were used for the developing of models for individual risk evaluation and prognosis. Clinico-radiologic status monitoring in the course of preoperative chemotherapy is instrumental in predicting risks as well as designing alternative strategies of treatment at earlier stages.

Assessment of cytological criteria for diagnosing osteosarcoma in dogs.

OBJECTIVES: To evaluate the specific cytological criteria of osteosarcomas in dogs. METHODS: Significant cytological characteristics of osteosarcoma and benign mesenchymal bone proliferations were determined from imprint smears of 25 dogs with osteosarcoma (group 1) and 20 dogs admitted for removal of surgical bone implants after uncomplicated healing of bone fractures (group 2). RESULTS: Mild to moderate cellular necrosis occurred frequently in patients with osteosarcoma. The cytoplasm of osteoblasts was pale blue to blue with a more pronounced basophilia in group 2. In 48 per cent of the patients in group 1, but none in group 2, osteoblasts showed a slight to moderate eosinophilic cytoplasmic granulation. In both groups, osteoblasts contained one red to pale blue nucleus with one or two grey-red to blue nucleoli in group 2. Forty-four per cent of animals in group 1 had osteoblasts with more than two nucleoli per nucleus. The median nuclear:cytoplasmic ratio was higher in group 1 (1:2.0) than in group 2 (1:3.5). Osteoblasts in group I were frequently seen to have a clumped chromatin pattern and showed significantly more criteria of malignancy (median six criteria per patient) than those in group 2 (median two criteria per patient). In group 1, mitoses of osteoblasts were detectable in 23 of 25 dogs, whereas only one dog in group 2 had evidence of mitotic osteoblasts. CLINICAL SIGNIFICANCE: Cytological criteria can be helpful in the diagnosis of canine osteosarcoma.

[Follow-up of patients with osteosarcoma and Ewing's sarcoma: a retrospective cost-benefit analysis]. / Nachsorge bei Patienten mit Osteosarkom und Ewing-Tumoren. Eine retrospektive Nutzenanalyse.

PURPOSE: Determination of the respective roles of clinical investigation, laboratory tests and various imaging techniques in the follow up of children and adolescents with osteosarcoma and Ewing's sarcoma. METHODS: In a retrospective monocenter analysis, charts of 72 patients with osteosarcoma and 47 patients with Ewing's sarcoma were reviewed with respect to ability of different diagnostic methods to detect the relapse, and correlated outcome. RESULTS: In about 25% of relapses, a second remission could be achieved. The most sensitive methods to detect a potentially curable relapse were clinical investigations and chest x-ray in the case of osteosarcoma and chest x-ray and whole body scintigraphy in the case of Ewing's sarcoma. CONCLUSIONS: The different value of diagnostic methods in the follow-up of the two illnesses may be explained by the different tumor biologies and by distinct therapeutic strategies for the treatment of relapses in the two tumor entities. However, an ongoing evaluation of current follow-up strategies is necessary to take into account new therapeutic developments which may shift the importance of certain imaging techniques.