A Retrospective Comparative Analysis of Outcomes and Prognostic Factors in Adult and Pediatric Patients with Osteosarcoma

Osteosarcoma is the most common primary bone malignancy in both children and adults. Despite introduction of intensive multimodal treatment with chemotherapy and surgery, outcomes are still poor, especially for patients with metastatic disease and adults. Hence, there is an ongoing need for better prognostic markers and outcome data to inform management decisions in both the adult and pediatric setting. Here, we retrospectively analyzed 112 patients with bone osteosarcoma treated at two large adult and pediatric tertiary academic centers between 1989 and 2019. Patients were divided into an adult (≥18 years) and pediatric (<18 years) cohort for comparison. Our aim was to evaluate predictors of outcomes in pediatric and adult patients, with a specific focus on the role of methotrexate when added to a combination of doxorubicin-cisplatin; the prognostic value of tumor necrosis after neoadjuvant chemotherapy; and outlining any differences in outcomes between adults and pediatric patients that could inform clinical management. Adult patients treated with methotrexate-doxorubicin-cisplatin and those treated with doxorubicin-cisplatin had similar 5-year PFS (26%, 95%CI: 45.5%–10% vs. 50%, 95%CI: 69.6%–26.2%, p = 0.1) and 5-year OS (63%, 95%CI: 82%–34%, vs. 78%, 95%CI: 90.6%–52.6%, p = 0.5). In the adult cohort, there was no difference between patients with ≥90% necrosis and <90% necrosis in either 5-year PFS (42%, 95%CI: 71.1%–11.3% vs. 38%, 95%CI: 57.7%–18.2%, p = 0.4) or 5-year OS (85%, 95%CI: 97.8%–33.4% vs. 56%, 95%CI: 76.8%–27.6%, p = 0.4). In the pediatric cohort, compared to patients with <90% necrosis, those with ≥90% necrosis had significantly better 5-year PFS (30%, 95%CI: 49.3%–14.1% vs. 55%, 95%CI: 73.9%–38.5%, p = 0.003) and 5-year OS (64%, 95%CI: 80.8%–41.1% vs. 78%, 95%CI: 92%–60.9%, p = 0.04). Adult and pediatric patients had similar 5-year OS (69%, 95%CI: 83.2%–49.8% vs. 73%, 95%CI: 83.2%–59.3%, p = 0.8) and 5-year PFS (37%, 95%CI: 52.4%–22.9% vs. 43%, 95%CI: 56.2%–30.4% p = 0.3) even though the proportion of patients with ≥90% necrosis after neoadjuvant chemotherapy was higher for children compared to adults (60.3% vs. 30%, OR: 3.54, 95%CI: 1.38–8.46, p = 0.006). In conclusion, in adult patients, the addition of methotrexate to doxorubicin and cisplatin did not correlate with a significant survival benefit, questioning the therapeutic value of methotrexate overall. Our study confirms the prognostic utility of percent tumor necrosis after neoadjuvant chemotherapy in pediatric patients but not in adult patients. Lastly, this is one of the few reported studies where patients with osteosarcoma younger and older than 18 years had similar PFS and OS.

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Clinical Features, Treatment, and Outcome in 102 Adult and Pediatric Patients with Localized High-Grade Synovial Sarcoma

Sarcoma ◽

10.1155/2011/231789 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 32

Author(s):

H. Al-Hussaini ◽

D. Hogg ◽

M. E. Blackstein ◽

B. O'Sullivan ◽

C. N. Catton ◽

...

Keyword(s):

Neoadjuvant Chemotherapy ◽

Synovial Sarcoma ◽

Surgical Resection ◽

Pediatric Patients ◽

Response Rate ◽

High Grade ◽

En Bloc ◽

Positive Surgical Margins ◽

Response To Neoadjuvant Chemotherapy

Background. There remains controversy on the routine use of chemotherapy in localized SS.Methods. The records of 87 adult (AP) and 15 pediatric (PP) patients with localized SS diagnosed between 1986 and 2007 at 2 centres in Toronto were reviewed.Results. Median age for AP and PP was 37.6 (range 15–76) and 14 (range 0.4–18) years, respectively. 65 (64%) patients had large tumours (>5 cm). All patients underwent en bloc surgical resection resulting in 94 (92.2%) negative and 8 (7.8%) microscopically positive surgical margins. 72 (82.8%) AP and 8 (53%) PP received radiotherapy. Chemotherapy was administered to 12 (13.8%) AP and 13 (87%) PP. 10 AP and 5 PP were evaluable for response to neoadjuvant chemotherapy, with response rate of10%and40%, respectively. 5-year EFS and OS was69.3±4.8%and80.3±4.3%, respectively, and was similar for AP and PP, In patients with tumors >5 cm, in whom chemotherapy might be considered most appropriate, relapse occurred in 9/19 (47%) with chemotherapy, compared to 17/46 (37%) In those without.Conclusions. Patients with localized SS have a good chance of cure with surgery and RT. Evidence for a well-defined role of chemotherapy to improve survival In localized SS remains elusive.

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Does Modality of Adjuvant Chemotherapy After Interval Surgical Debulking Matter in Epithelial Ovarian Cancer?: An Exploratory Analysis

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000066 ◽

2014 ◽

Vol 24 (3) ◽

pp. 461-467 ◽

Cited By ~ 5

Author(s):

Nashmia Joudallah Al Mutairi ◽

Tien Le

Keyword(s):

Ovarian Cancer ◽

Neoadjuvant Chemotherapy ◽

Epithelial Ovarian Cancer ◽

Cox Regression ◽

Group Versus ◽

Progression Free Survival ◽

Outcome Data ◽

Categorical Variables ◽

Surgical Debulking

ObjectivesThis article aimed to study the role of adjuvant intraperitoneal (IP) chemotherapy after neoadjuvant chemotherapy and optimal interval surgical debulking.MethodAll patients with epithelial ovarian cancer treated with neoadjuvant chemotherapy were retrospectively reviewed from 2007 to 2009. Demographics, related diseases, and survival outcome data were abstracted from the medical records. χ2statistics were applied to categorical variables. Cox regression was used to model progression-free survival (PFS), adjusting for age, residual status, and use of adjuvant IP chemotherapy. AllPvalues less than 0.05 were considered statistically significant.ResultsSixty-five patients were reviewed. The median age was 63.3 years. The majority had stage III disease with serous histology. Optimal residual (<1 cm) after interval debulking was achieved in 34 (54%) of 63 patients. Sixteen patients chose to receive adjuvant IP chemotherapy. The median follow-up was 26.2 months. Fifty-one patients had progressed, with a median PFS of 17.5 months. Adjuvant IP chemotherapy was not predictive of PFS (hazard ratio, 0.91; 95% confidence interval [CI], 0.24–3.44;P= 0.89). The estimated median overall survival was 37.8 months (95% CI, 29.9–45.7) in the intravenous group versus 48.1 months (95% CI, 37.9–58.3) in the IP-treated patients (P= 0.162).ConclusionsAdjuvant IP chemotherapy was not predictive of survival after neoadjuvant chemotherapy in our small exploratory study. The role of IP chemotherapy in this setting needs to be further studied in a larger prospective patient cohort.

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The AG Genotype of the Wilms Tumor-1 rs16754 SNP Is Associated with Poor Outcome in Pediatric AML Patients Treated with Stem Cell Transplantation but Not in Adults

Blood ◽

10.1182/blood.v118.21.5237.5237 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5237-5237

Author(s):

Hala Abalkhail ◽

Hassan El-Solh ◽

Amal Alseraihy ◽

Mouhab Ayas ◽

Ali Al-Ahmari ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Pediatric Patients ◽

Wilms Tumor ◽

Adult Patients ◽

Hematopoietic Stem ◽

Wilms Tumor 1 ◽

Pediatric Aml

Abstract Abstract 5237 The synonymous single nucleotide polymorphism rs16754 in the Wilms Tumor-1 gene (WT1) has been reported to correlate with outcome in adult patients with acute myeloid leukemia (AML) when treated with intensive chemotherapy. Specifically the GG genotype is significantly associated with favorable outcome, but also the AG genotype has been reported to be associated with better outcome as well. The clinical relevance of the rs16754 SNP in pediatric AML patients is far from clarified. In addition, it is not known whether allogeneic hematopoietic stem cell transplantation (HSCT) can modify the role of this SNP and its association with outcome. Methods: Genotyping of the SNP by direct sequencing of the exon 7 was performed on bone marrow samples from 86 AML patients (38 pediatrics and 48 adults). All patients were treated with HSCT. Most patients (39 adults and 28 pediatrics) were transplanted in first remission (CR1). The median age was 25 years (range: 14–54) for adults and 8 years (range: 8 months–14 years) for the pediatric group. Results: In pediatric AML, we detected the AA genotype in 22 patients (53%), the GG genotype in 2 patients (5%) and the remaining (42%) had AG genotype. In the adult patients, the AA genotypye was present in 26 patients (54%), GG genotype in 3 (6%) patients, and the AG genotype in the remaining patients (39%). A similar distribution was observed in the normal population (58%, 12%, 30%, for AA, GG, and AG, respectively). In pediatric patients, the AG genotype significantly correlated with shorter overall survival (OS) (P=0.04) and event free survival (EFS) (P=0.04) when compared with the patients with AA genotype. In contrast, in adult AML, groups with AG and AA geneotypes completely overlapped for OS and EFS. When only patients treated with HSCT in CR1 were considered, the pediatric patients showed the same trend (P=0.07), but there was no correlation with survival in the adult group. This analysis included patients with intermediate and adverse risk cytogenetics. AG genotype was not a predictor of outcome in multivariate model incorporating cytogenetics and the WT1 genotype. The patients with the GG genotype were too few for analysis. Conclusion: This data supports the concept that the biology of AML in pediatric patient is different from that in adults. The role of this synonymous SNP in AML needs further exploration, especially investigating the potential that this SNP may have some effects on the host and not only the disease. Disclosures: No relevant conflicts of interest to declare.

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Evaluating the Trends of Bloodstream Infections among Pediatric and Adult Patients at a Teaching Hospital of Kathmandu, Nepal: Role of Drug Resistant Pathogens

Canadian Journal of Infectious Diseases and Medical Microbiology ◽

10.1155/2017/8763135 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 2

Author(s):

Narayan Prasad Parajuli ◽

Hridaya Parajuli ◽

Roshan Pandit ◽

Jyotsna Shakya ◽

Puspa Raj Khanal

Keyword(s):

Staphylococcus Aureus ◽

Antimicrobial Resistance ◽

Blood Culture ◽

Teaching Hospital ◽

Pediatric Patients ◽

Bloodstream Infections ◽

Adult Patients ◽

Beta Lactamase ◽

Drug Resistant

Bloodstream infections (BSIs) are among the significant causes of morbidity and mortality for patients of all age groups. However, very little is known about the trends of bacterial bloodstream infections and antimicrobial susceptibilities among pediatric and adult population from Nepal. In this study, we have investigated the different etiological agents responsible for bloodstream infections among pediatric and adult patients and the role of drug resistant organisms in these infections at a tertiary care teaching hospital of Kathmandu, Nepal. A total of 3,088 blood culture specimens obtained from pediatric and adult patients suspected to have bloodstream infections were processed by standard microbiological methods. Significant bacterial pathogens were identified by morphological, biochemical, and serological methods as suggested by American Society for Microbiology. In vitro antimicrobial susceptibility testing was performed by Kirby-Bauer disk diffusion method and interpreted according to the guidelines of Clinical and Laboratory Standards Institute. Overall, incidence of bloodstream infections among the suspected patients was 7.48%. Pediatric patients (n=90, 9.37%) were the significant subgroup of patients affected with bloodstream infections compared to adults (p<0.05, CI-95%). Gram positive (n=49, 54.4%) bacteria in pediatric and gram negative bacteria (n=141, 78.7%) in adult patients were the most common isolates for BSI.Staphylococcus aureus(n=41, 45.6%) in pediatric patients andSalmonella enterica(n=40, 28.3%) in adult patients were the leading pathogens. Trends of antimicrobial resistance among isolated bacterial strains were significantly high in adults compared to pediatric patients. Methicillin resistantStaphylococcus aureus(MRSA) (31.4%), extended spectrum beta-lactamase (ESBL) (12.5%), and metallo-beta-lactamase (MBL) (3.9%) producing gram negatives were major resistant strains. Our study shows higher rates of bloodstream infections in pediatric patients compared to adult patients. Alarming rates of antimicrobial resistance among blood culture isolates is a serious issue. Prompt and accurate diagnosis and rational antimicrobial therapy are extremely needed.

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Comparison Of Intravenous With Oral Busulfan In Allogeneic Hematopoietic Stem Cell Transplantation With Myeloablative Conditioning Regimens For Pediatric Acute Leukemia

Blood ◽

10.1182/blood.v122.21.3397.3397 ◽

2013 ◽

Vol 122 (21) ◽

pp. 3397-3397

Author(s):

Motohiro Kato ◽

Yoshiyuki Takahashi ◽

Daisuke Tomizawa ◽

Yasuhiro Okamoto ◽

Jiro Inagaki ◽

...

Keyword(s):

Stem Cell ◽

Clinical Outcome ◽

Acute Leukemia ◽

Pediatric Patients ◽

Myeloablative Conditioning ◽

Hematopoietic Stem ◽

Significant Survival ◽

The Difference

Abstract Recently, intravenous busulfan (iv-BU) has replaced oral-BU, which can suppress variety of bioavailability. Also, iv-BU showed less hepatic toxicity by avoiding the hepatic first-pass effect of oral-BU. Previous reports showed that the use of iv-BU reduced early complications and decreased early non-relapse mortality (NRM). Some reports demonstrated that iv-BU may provide better overall survival (OS) in adult with malignant diseases. Although several reports have been published on pediatric patients using iv-BU, the number of patients included was small, and the reports mainly focused on acute toxicity or early clinical outcome because of a short follow-up period. Thus, the role of iv-BU in HSCT for pediatric patients with acute leukemia is yet to be determined. In this study, to compare clinical outcome of HSCT with iv-BU and oral-BU, we retrospectively analyzed HSCT based on data reported to the Japan Society for Hematopoietic Cell Transplantation (JSHCT) registry. The patients were selected according to the following criteria: (1) patients diagnosed with either acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML), (2) aged 15 years or younger when receiving HSCT, (3) BU-based myeloablative (more than 8 mg/kg) preconditioning regimens, and (4) HSCT performed between 2000 and 2010. Therefore, we analyzed 460 children with iv-BU (n = 198) or oral busulfan (BU) (n = 262) receiving hematopoietic stem cell conditioning transplantation (HSCT) with BU-based myeloablative conditioning for acute leukemia. The median age at HSCT was 4 years (range, 0–15 years). The median follow-up period was 1,828 days (range, 85–4,619 days) after HSCT in all the surviving patients, and 1,185 days (range, 100–3,759 days) after HSCT in the iv-BU patients. Although OS with iv-BU and oral-BU at day 100 after HSCT was 72.5 ± 3.2% and 66.9 ± 2.9%, respectively, OS at 3 years after HSCT was similar (iv-BU, 53.4 ± 3.7%; oral-BU, 55.1 ± 3.1% ), and the log-rank test for OS did not show statistically significant difference (p = 0.77) (Figure 1a). The result was concordant even when an analysis was limited to patients with ALL or AML. OS at 3 years for patients with ALL using iv-BU (n = 90) and oral-BU (n = 151) was 56.4 ± 5.5% and 54.6 ± 4.1, respectively (p = 0.51) (Figure 1b). OS at 3 years for patients with AML using iv-BU (n = 108) and oral-BU (n = 111) was 51.0 ± 5.0% and 55.8 ± 4.8%, respectively (p = 0.83) (Figure 1c). The similarity of OS was reproduced even with the limited cohort of 247 patients who received HSCT after 1st CR or 2nd CR without prior HSCT. OS at 3 years was 78.3 ± 4.2% for iv-BU patients (n = 98) and 78.7 ± 3.4% for oral-BU patients (n = 149) and the difference was not statistically significant (p = 0.66). Multivariate analysis also showed no significant survival advantage with iv-BU. Cumulative incidence of relapse at 3 years with iv-BU was similar with that of oral-BU (39.0 ± 3.6% and 36.4 ± 3.1%, respectively) (p = 0.67). Cumulative incidence of NRM at 3 years was 16.6 ± 2.7% with iv-BU and 18.3 ± 2.5% with oral-BU (p = 0.51). The iv-BU group showed a tendency toward higher engraftment probability at day 60 (96.0 ± 1.5%) compared with the oral-BU group (89.3 ± 2.0%), but the difference was not statistically significant (p = 0.22) This study was a retrospective study using registry data, and there are some limitations of our data. For example, as selection of iv-BU or oral-BU was strongly associated with the transplantation period, which may have introduced bias. Further prospective studies are required to establish an optimal allogeneic HSCT treatment strategy for pediatric patients with acute leukemia. In conclusion, our study provides valuable information on the role of iv-BU in myeloablative HSCT for pediatric acute leukemia. In children, iv-BU could not show significant survival improvement in outcome of acute leukemia. Disclosures: No relevant conflicts of interest to declare.

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