Group Of Solid Tumors Research Articles

Assessment of enrollment characteristics for Children’s Oncology Group (COG) upfront therapeutic clinical trials 2004-2015.

6564 Background: Improvements in pediatric cancer survival are attributed to cooperative clinical trials. Under representation of specific demographic groups has been described in adult and pediatric cancer and poses a threat to the generalizability of trial results. A comprehensive evaluation of data provided by the Children’s Oncology Group (COG) of upfront trial enrollment for US patients 0 to 29 years old between 2004 and 2015 was performed to assess for disparities in participation. Methods: Estimates of cancer cases were calculated using the Surveillance, Epidemiology, and End Results registry and the US Census and compared to observed COG cases. Percent enrollment and Standardized Ratios of enrollment were calculated across various demographic, disease, and socioeconomic groups. The COG website was utilized to quantify available upfront trials during the study period and assess age eligibility criteria. Results: 21.3% of estimated US cancer patients age 0 to 19 years enrolled on COG trials. Younger patients were consistently more represented across disease types and race/ethnicities. Patients with hematologic malignancies were more represented compared to solid and central nervous system (CNS) tumors. Conclusions: COG clinical trial enrollment rates are declining, which may be due to challenges in pediatric drug development, difficulty designing feasible trials for highly curable diseases, and issues in ensuring trial availability for the heterogeneous group of solid and CNS tumors. Though racial/ethnic groups and county-level socioeconomic factors were proportionally represented, under representation of the adolescent/young adult (AYA) population and younger patients with solid and CNS tumors remain significant concerns. Targeted enrollment efforts should focus on the identified subgroups and further research should evaluate AYA enrollment across all available trials to provide continued treatment advances for all patients.

Multiplatform molecular profiling: Observational study to determine the effect of treatment selection in advanced or refractory metastatic solid tumors.

e14730 Background: To assess the clinical benefit of treatment in advanced and refractory solid tumors utilizing evidence-guided molecular profiling (MP) of tumors in routine clinical practice. Methods: This retrospective observational study was conducted on patients with advanced or refractory metastatic solid tumors, whose tumor biopsy samples were referred for profiling using a multi-platform tumor profiling service (Caris Molecular Intelligence) between January 2014 and April 2017. Specific testing was performed per physician’s request and included a combination of next-generation sequencing (NGS), protein expression (IHC), gene amplification (CISH or FISH), and/or RNA fusion analysis. Results: Data of twenty five patients with solid tumors was analyzed (median age of 58 years, range 25-82 years). Patients had received a median of 2 prior lines of therapy (range 0-6). In evaluable patients, 1 (4%) patient had a complete response, 10 (46%) patients had a partial response, 5 (23%) had stable disease and 6 (27%) had progressive disease, giving a disease control rate of 73%. The majority of patients received chemotherapy (CT) alone (13; 56%). Five patients received CT combined with targeted therapy (TT), 2 received TT alone, 2 received TT combined with hormone therapy (HT), 2 have received immunotherapy and 1 received HT alone. Two patients were not evaluable for response. In responding patients, median duration of response was 7 months (3-18 months). Conclusions: The result of this study show that treatment based on Broad tumor profiling in a select group of advanced and refractory solid tumors was associated with a high disease control rate.

SPORADIC AND HEREDITARY FORMS OF MULTIPLE PRIMARY MALIGNANT TUMORS IN CHILDREN

The article presents the features of the clinical manifestation of multiple primary sporadic and heritable malignant tumors in 104 children who observed at Pediatric Oncology and Hematology Research Institute of «NN Blokhin's National Medical Research Center of Oncology» from 1998 to 2012. The age of patients at the time of occurrence of the second malignant tumor ranged from 2.8 to 28 years and averaged 15.6 years. The second neoplasia occurred significantly more frequently in the group of primary hemoblastosis, compared with the group of solid tumors - 8.7% versus 3.4%, respectively (p <0.0001). In children with multiple primaries, were found tumors that occur in common the most frequency. Retinoblastoma patients have an increased risk of developing sarcoma. Patients with Hodgkin's lymphoma have an increased risk of developing leukemia. In surviving children after treatment of the first neoplasia the thyroid, bone tissue and breast have a specific risk for the development of metachronous cancer and are target organs for control. Children with new hematopoietic tumors may be candidates for metachronous development of leukemia and bone tissue tumors. The using methods Next Generation Sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) revealed germinal mutations in 12 children with of multiple primary tumors. The mutations in the TP53, RB1, CHEK2, FANCN/PALB2, MLH1, PMS2 genes identified in patients were associated with hereditary syndromes and an increased risk of developing second tumors, among which: sarcomas, brain tumors, hematopoietic tumors were the most frequent. It was shown that the second tumors can appear at the any age. Children who survived the treatment of the first tumor in later life should be monitored annually. Clinical management of children with multiple primary tumors requires a multidisciplinary approach.

Multifactorial Contribution of Notch Signaling in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) defines a group of solid tumors originating from the mucosa of the upper aerodigestive tract, pharynx, larynx, mouth, and nasal cavity. It has a metastatic evolution and poor prognosis and is the sixth most common cancer in the world, with 600,000 new cases reported every year. HNSCC heterogeneity and complexity is reflected in a multistep progression, involving crosstalk between several molecular pathways. The Notch pathway is associated with major events supporting cancerogenic evolution: cell proliferation, self-renewal, angiogenesis, and preservation of a pro-oncogenic microenvironment. Additionally, Notch is pivotal in tumor development and plays a dual role acting as both oncogene and tumor suppressor. In this review, we summarize the role of the Notch pathway in HNSCC, with a special focus on its compelling role in major events of tumor initiation and growth.

Secondary Malignancies after Hematopoietic Cell Transplantation in Pediatric Patients; A Single Center Experience

Background Hematopoietic cell transplantation (HCT) is a standard therapeutic modality for many hematological malignant and nonmalignant disorders. Advances in supportive care after HCT have led to improvement in survival. Secondary malignant neoplasm (SMN) is a devastating late effect after HCT that is associated with significant morbidity and high mortality. Methods Records of 1910 pediatric patients (pts) ≤14 years of age who underwent HCT at our center between 1995-2015 were reviewed to study the incidence of SMN after HCT in our population and potential risk factors. Factors studied were age at HCT, gender, indication of HCT, number and type of transplant, stem cells source, GVHD prophylaxis regimen, use of radiation-based conditioning regimens. Results A total of 2034 HCT were performed on 1910 pts; 1789 (93.7%) had 1 transplant, and 121(6.3%) ≥2 transplants; 25 pts (1.3%) developed SMN. Fifteen had solid tumors (Group A), 6 had leukemia or lymphoma (Group B) and 4 had post-transplant lymphoproliferative disorder (PTLD; Group C). Median time to development of SMN from first HCT was 100.8 months (range, 3.7-244.8). Approximately three quarters of pts who developed SMN were transplanted for non-malignant disorders (18 of 25, 72%), and amongst non-malignant disorders, bone marrow failure syndromes pts had the highest incidence (10 of 18, 55.6%, P-value 0.008). Twelve pts (48%) who developed SMN received radiation-based conditioning regimen (p-value 0.001). The 10-year probability of overall survival (OS) at 10-years for those who developed SMN was not significantly different than OS in those who did not (0.748±0.089 vs. 0.664±0.011, p-value: 0.154). Among those who developed SMN, 10-year OS was better in Group A compared to Group B and Group C (0.929±0.069, 0.625±0.213 and 0.250±217 respectively; p-value: 0.015). Conclusion SMN developed in 1.3% of our pts post HCT; use of radiation in the conditioning regimen appears to be a significant risk factor.`

Myeloid/Histiocytic Neoplasms Associated with Germ Cell Tumors Harbor Shared Genetic Abnormalities Indicating a Clonal Relationship, Unique Molecular Pathogenesis and Cellular Origin

IntroductionNeoplasms of different lineages that arise in the same patient and show a clonal relationship are exceedingly rare, but have been described in instances of histiocytic and myeloid/lymphoid neoplasms (Durham BH, et al. Blood 2017;130(2):176-80; Ansari J, et al. Eur J Haematol 2016;97(1):9-16). The clonal relationships can be demonstrated by shared genetic abnormalities such as translocations, somatic mutations, and other chromosomal level alterations. Nevertheless, a clonal link between germ cell tumors (GCT), a group of solid tumors derived from primitive stem cells, and hematologic malignancies has been less well-characterized. Relevant literature has mostly reported associations of GCT with acute leukemias, without a comprehensive assessment of genetic alterations (Mukherjee S et al. Ann Hematol 2017;96: 1435-39). To further characterize this phenomenon, we identified a small cohort of patients diagnosed with both GCT and any myeloid/histiocytic neoplasm. We evaluated their molecular and cytogenetic alterations, identifying shared and unique abnormalities, providing evidence of a clonal relationship between these two groups of neoplasms, which traditionally represent different cellular origins.MethodsA search of the pathology database at a major referral center (Memorial Sloan-Kettering Cancer Center) was performed to identify patients diagnosed with GCT between 2012-2018, and had at least 1 prior or subsequent bone marrow biopsy. The medical records were reviewed for details of clinical presentations and evidence of myeloid neoplasm, with corresponding morphologic, cytogenetic, and molecular findings. The findings were correlated with the genetic alterations detected in the GCT during diagnostic work-up. Cytogenetic analyses include karyotyping, fluorescence in situ hybridization (FISH) studies for common abnormalities among myeloid neoplasms, and single nucleotide polymorphism (SNP) array for copy number gain/loss and copy neutral-loss of heterozygosity (CN-LOH). Molecular analyses include an amplicon capture-based next generation sequencing (NGS) assay for 49 genes relevant for hematologic malignancies, and MSK-IMPACTTM, a hybrid capture-based NGS assay for mutation and copy number alteration in 400+ genes. Somatic nature of the identified variants was confirmed on MSK-IMPACTTM by germline variant filtering with the aid of appropriate normal control samples (blood or nail).Results8 patients with GCT diagnoses showed marrow findings consistent with or suspicious for involvement by myeloid/histiocytic neoplasms, with clinical presentations not typical for therapy-related myeloid neoplasms. The patients were predominantly male (n=6) and young (age range: 13-55, median=26.5). The GCT included mixed GCT (n=6), mature teratoma (n=1) and immature teratoma (n=1). The primary sites of involvement were mediastinum (n=4), testes (n=2), and ovaries (n=2). In all cases, the myeloid/histiocytic neoplasms and GCT were diagnosed in close proximity in time (range: <1 to 24 months). So far, cytogenetic and molecular data in 4 patients with mediastinal-based tumors showed shared alterations between the GCT and myeloid/histiocytic neoplasms, including isochromosome 12p in 3 patients, an alteration characteristic of GCT. Other shared alterations observed included identical mutations in TP53, PIK3CD, KRAS, BCOR; trisomy 1, 8, 21; gain of 21q; loss of 13q; and CN-LOH of 2q, 5q, 17p. Interestingly, in all 4 patients, the GCT and myeloid/histiocytic neoplasm each showed additional unique genetic alterations.ConclusionThese findings suggest that a subset of patients with GCT can develop clonally-related myeloid/histiocytic neoplasms, with a relatively short latency period. The genetic changes seen in our cases are relatively less common in conventional myeloid neoplasms, suggesting unique molecular pathogenesis. Yolk sac component in the GCT, which has been described to harbor hematopoietic precursor cells, may contribute to pathogenesis (Orazi A, et al Cancer 1993;71(12):3873-81). Although the detailed pathogenic mechanism remains uncertain, we observed that in the cohort, the GCT and myeloid/histiocytic neoplasm each harbored additional unique genetic changes. This suggests the presence of a common neoplastic progenitor giving rise to neoplasms of different lineages, which subsequently accumulated additional alterations. [Display omitted] DisclosuresHo:Invivoscribe, Inc.: Honoraria. Yabe:Y-mAbs Therapeutics: Consultancy. Arcila:Invivoscribe, Inc.: Consultancy, Honoraria.

Soft Tissue Sarcoma Cancer Stem Cells: An Overview.

Soft tissue sarcomas (STSs) are an uncommon group of solid tumors that can arise throughout the human lifespan. Despite their commonality as non-bony cancers that develop from mesenchymal cell precursors, they are heterogeneous in their genetic profiles, histology, and clinical features. This has made it difficult to identify a single target or therapy specific to STSs. And while there is no one cell of origin ascribed to all STSs, the cancer stem cell (CSC) principle—that a subpopulation of tumor cells possesses stem cell-like properties underlying tumor initiation, therapeutic resistance, disease recurrence, and metastasis—predicts that ultimately it should be possible to identify a feature common to all STSs that could function as a therapeutic Achilles' heel. Here we review the published evidence for CSCs in each of the most common STSs, then focus on the methods used to study CSCs, the developmental signaling pathways usurped by CSCs, and the epigenetic alterations critical for CSC identity that may be useful for further study of STS biology. We conclude with discussion of some challenges to the field and future directions.

1631P - Efficacy and safety of apatinib in advanced sarcoma

Background: Sarcoma constitutes a heterogeneous group of rare solid tumors and has no standard second-line treatment. Anti-angiogenesis tyrosine kinase inhibitors have shown promising efficacy for advanced sarcoma after failure of first-line chemotherapy. Apatinib is a highly selective vascular endothelial growth factor receptor 2 (VEGFR-2) antagonist from China. In the present study, we retrospectively assessed apatinib for safety and activity in advanced sarcoma patients from our cancer center. Methods: Patients with advanced sarcomas treated with apatinib 250-500mg daily between August 2015 and February 2018 were retrospectively analyzed. Objective response was determined according to RECIST 1.1 criteria, progression-free survival (PFS) was estimated by the Kaplan-Meier curves and safety profile was analyzed. Results: In total, 52 patients were treated with apatinib and 37 patients (23 males and 14 females) were included for analysis, including 7 alveolar soft part sarcoma (ASPS), 5 PNET/Ewing’s sarcoma, 4 osteosarcoma, 4 chondrosarcoma, 3 synovial sarcoma, 4 undifferentiated pleomorphic sarcoma, 4 leiomyosarcoma, 2 angiosarcoma,1 rhabdomyosarcoma, 1 chordoma, 1dedifferentiated liposarcoma and 1 clear cell sarcoma. 5 (13.5%) patients received apatinib as first-line treatment, 17 (45.9%) and 15 (40.5%) were treated with apatinib as second line or later therapy respectively.18 (48.6%) achieved tumor regression, 1 patient with ASPS had complete response, 8 (21.6%) experienced partial response, and disease was stable in 21 (56.8%) patients. The disease control rate was 100% in 5 patients with ASPS. The median PFS for all patients was 12 months, and median PFS of patients except ASPS was 5.9 m. The most frequent treatment-related adverse events included hypothyroidism [11 (29.7%)], Proteinuria [8 (21.6%)], hypertension [11 (29.7%)), hand-foot syndrome [19 (51.4%)], diarrhea [9 (24.3%)], fatigue [5 (13.5%)], hemorrhage [4 (10.8%)], anorexia [5 (13.5%)], oral ulcer [3 (5.4%)], rash [2 (8.1%)], bleaching hair [2 (5.4%)] and aerothorax [2 (5.4%)]. Conclusions: Apatinib may be effective and tolerable in advanced sarcoma, especially in ASPS. Legal entity responsible for the study: Union Hospital, Tongji Medical College, Huazhong University of Science and Technology. Funding: Clinical Research Physician Program of Tongji Medical College, HUST. Disclosure: All authors have declared no conflicts of interest.

Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma

BackgroundSoft tissue sarcomas are a heterogeneous and rare group of solid tumors of mesenchymal origin that can arise anywhere in the body. Although surgical resection is the mainstay of treatment for patients with localized disease, disease recurrence is common and 5-year overall survival is poor (~ 65%). Both radiation therapy and conventional chemotherapy are used to reduce local and distant recurrence. However, the utility of radiation therapy is often limited by disease location (in the case of retroperitoneal sarcomas, for instance) while systemic therapy with conventional lines of chemotherapy offer limited efficacy and are often poorly tolerated and associated with significant toxicity. Within the past decade, major advances have been made in the treatment of other malignancies including melanoma, renal cell carcinoma, and non-small cell lung carcinoma with the advent of immune-checkpoint inhibitors such as ipilimumab (anti-CTLA4), pembrolizumab (anti-PD1), and nivolumab (anti-PD1). The recently published SARC028 (NCT02301039), an open label, phase II, multicenter trial of pembrolizumab in patients with advanced bone and soft tissue sarcomas reported promising activity in select histologic subtypes of advanced STS, including undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma.MethodsThere is a clear need for novel and effective adjuncts in the treatment of STS. We hypothesize that immune checkpoint blockade will be effective in patients with surgically resectable primary or locally recurrent dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma when administered in the neoadjuvant setting. The primary aim of this phase II, single-center, open label, randomized non-comparative trial is to determine the pathologic response to neoadjuvant nivolumab monotherapy and combination nivolumab/ipilimumab in patients with resectable dedifferentiated liposarcoma of the retroperitoneum or undifferentiated pleomorphic sarcoma of the trunk or extremity treated with concurrent standard of care neoadjuvant radiation therapy.DiscussionThis study will help define the role of single agent anti-PD1 and combination anti-CTLA4 and anti-PD1 therapy in patients with surgically resectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma.Trial registrationClinicalTrials.govNCT03307616, registered October 12, 2017.

Social adjustment in adolescent survivors of pediatric central nervous system tumors: A report from the Childhood Cancer Survivor Study.

The purpose of this study was to examine the prevalence and predictors of social difficulties in adolescent survivors of central nervous system (CNS) tumors. Six hundred sixty-five survivors of CNS tumors (53.8% male and 51.7% treated with cranial radiation therapy [CRT]), who had a current median age of 15.0 years (range, 2.0-17.0 years) and were a median of 12.1 years (range, 8.0-17.7 years) from their diagnosis, were compared with 1376 survivors of solid tumors (50.4% male), who had a median age of 15.0 years (range, 12.0-17.0 years) and were a median of 13.2 years (range, 8.3-17.9 years) from their diagnosis, and 726 siblings (52.2% male), who had a median age of 15.0 years (range, 12.0-17.0 years). Social adjustment was measured with parent-proxy responses to the Behavior Problems Index. Latent profile analysis defined social classes. Multinomial logistic regression, adjusted for age, sex, and age at diagnosis, identified predictors of class membership. Path analyses tested mediating effects of physical limitations, sensory loss, and cognitive impairment on social outcomes. Caregivers reported that survivors of CNS tumors were more likely to have 0 friends (15.3%) and to interact with friends less than once per week (41.0%) in comparison with survivors of solid tumors (2.9% and 13.6%, respectively) and siblings (2.3% and 8.7%, respectively). Latent profile analysis identified 3 social classes for survivors of CNS tumors: well-adjusted (53.4%), social deficits (16.2%), and poor peer relationships (30.4%). However, 2 classes were identified for survivors of solid tumors and siblings: well-adjusted (86.2% and 91.1%, respectively) and social deficits (13.8% and 8.9%, respectively). CRT predicted class membership for CNS survivors (odds ratio [OR] for poor peer relationships, 1.16/10 Gy; 95% confidence interval [CI], 1.08-1.25; OR for social deficits 1.14/10 Gy; 95% CI, 1.04-1.25; reference, well-adjusted). Cognitive impairment mediated the association between all social outcomes and CRT (P values < .001). Almost 50% of survivors of CNS tumors experience social difficulties; the pattern is unique in comparison with solid tumor and sibling groups. Cognitive impairment is associated with increased risk, and this highlights the need for multitargeted interventions.

Oral Nutritional Supplementation in Children Treated for Cancer in Low- and Middle-Income Countries Is Feasible and Effective: the Experience of the Children's Hospital Manuel De Jesus Rivera "La Mascota" in Nicaragua.

Children with cancer are particularly vulnerable to malnutrition, which can affect their tolerance of chemotherapy and outcome. In Nicaragua approximately two-thirds of children diagnosed with cancer present with under-nutrition. A nutritional program for children with cancer has been developed at “La Mascota” Hospital. Results of this oral nutritional intervention including difficulties, benefits, and relevance for children treated for cancer in low− and middle-income countries are here reported and discussed.

Soft tissue sarcomas in the precision medicine era: new advances in clinical practice and future perspectives.

Soft tissue sarcomas (STSs) represent a rare and heterogeneous group of solid tumours derived from mesenchymal progenitors and account for 1% of all adult malignancies. Although in the last decade anthracycline-based chemotherapy single agent or in combinations has been able to improve clinical benefits, prognosis is still poor and STSs represent an important unmet medical need. Continuous advances in cancer genetics and genomics have contributed to change management paradigms of STSs as it occurred for other solid tumours. Several treatments have been recently developed with the specific aim of targeting different cell pathways and immune-checkpoints that have been recognized to drive tumour progression. The following attempts to provide a review of literature focusing on the available data concerning novel treatments and future prospective for the management of metastatic STSs.

399P - Prognostic impact of new T1 descriptors in TNM classification of non-small cell lung cancer

Background: In the 8th edition of the tumor, node and metastasis (TNM) classification for non-small cell lung cancer (NSCLC), T category is defined by tumor size, only the size of the solid component size on computed tomography (CT) or the size of the invasive component size at pathologic examination. Thus, whether patients with solid tumors should be treated similarly to those with part-solid tumors with solid components of equal size is unclear. In the present study, we assessed the prognostic value of the newly proposed T1 descriptors with regard to solid component size in patients with NSCLC. Methods: We included 255 consecutive patients who were diagnosed with clinical stage IA NSCLC according to the TNM 7th edition, and underwent lobectomies between January 2005 and December 2010 at our medical center. We assessed the prognostic value of the newly proposed T1 descriptors with regard to solid component size. Survival analysis was performed between solid tumor group and part-solid tumor group for all patients and for their propensity score-matched pairs. In addition, the new staging system was used for classification and comparison of survival. Results: Chest CTs found 7 non-solid tumors, 123 part-solid tumors and 125 solid tumors. Mean whole tumor size and maximum diameter of solid components were 20 mm (range: 0–30 mm) and 17 mm (0–30 mm), respectively. Mean duration of follow-up after surgical resection was 59 months. For the entire cohort, the 5-year overall survival (OS) rate was 77.2%, and the 5-year disease-free survival (DFS) rate was 72.1%. The 5-year OS and DFS differed significantly between patients with solid tumors (5-year OS: 71.2%; 5-year DFS: 65.4%) and the part-solid tumor group (5-year OS: 83.2%; 5-year DFS: 78.2%). However, among 81 propensity score-matched pairs, (including matching for solid component size), OS and DFS did not significantly differ between the solid and part-solid tumor groups. Using the 8th TNM edition, 5-year OS rates were patients diagnosed with cIA1 disease: 88.0%; cIA2: 79.4%; and cIA3: 67.6%. Conclusions: The propensity score matching based on solid component size showed no significant difference in survival between the solid and part-solid tumor groups. The 8th edition T descriptors have prognostic value for NSCLC. Legal entity responsible for the study: Tomoyoshi Takenaka Funding: None Disclosure: All authors have declared no conflicts of interest.

Treatment and survival of childhood neuroblastoma: Evidence from a population-based study in the United States

ABSTRACTBackground: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors, that are treated per risk profile. We sought to describe treatment patterns and survival using population-based data from throughout the United States.Materials and Methods: Using the National Cancer Institute (NCI)'s Patterns of Care data, we analyzed treatment provided to newly diagnosed, histologically confirmed neuroblastoma patients in 2010 and 2011, registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians contacted for verification. Application of the Children's Oncology Group (COG)'s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making provided insight to community-based treatment patterns. Kaplan-Meier survival analyses, based on 5-years of follow-up, were also performed.Results: 76% of the 250 patients were enrolled on an open/active clinical trial. All low-risk patients received surgery. Most intermediate-risk patients (81%) received a chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, myeloablative chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. 21% patients had died at the end of the maximum 60-month follow-up period. The 5-year estimated survival rates were lower for patients diagnosed with stage 4 disease, unfavorable DNA ploidy, MYCN gene amplification or classified as high-risk.Conclusion: Most neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy received by these patients.

A population-based analysis of a rare oncologic entity: Malignant pancreatic tumors in children

To examine the clinicopathological characteristics and prognosis of pediatric patients with malignant pancreatic tumors in a population-based cohort. The Surveillance, Epidemiology, and End Results (SEER) database was utilized to identify all pediatric patients with malignant pancreatic tumors, diagnosed between 1973 and 2013. Kaplan-Meier analysis was performed to determine median and five-year overall survival (OS) rates. Univariate survival analysis was executed using the log-rank test. Cox proportional hazards model was used to identify variables independently associated with mortality. A total of 114 patients with pancreatic malignancies were identified. Median patient age was 16years and the majority of patients were white (64%) females (61.4%). The most prevalent histologic subtype was neuroendocrine tumors (35.1%), whereas pancreatoblastoma was more common during the first decade of life (P<0.001). Distant metastases were noted in 41.7% of the patients, while 33.3% and 25% had localized and regional disease respectively. Five-year OS rates were 77%, 66.4% and 64.8% for patients with pancreatoblastoma, neuroendocrine and epithelial tumors respectively. No death was observed in the solid pseudopapillary tumor group. Only history of having cancer-directed surgery (CDS) was significantly associated with lower overall mortality (HR: 5.1, 95% CI: 2.1, 12.4). Pancreatic malignancies are rare in children. Their prognosis is variable and only CDS was independently associated with superior survival. Prognosis study, Level II.

Patterns of care in treating childhood neuroblastoma: Evidence from a population level study (SEER) in the United States.

e22011 Background: Childhood neuroblastoma describes a heterogeneous group of extracranial solid tumors. This heterogeneity is reflected in the sequence and variety of treatment modalities administered. We describe the treatment pattern and survival of childhood neuroblastoma patients using population-based data in the United States. Methods: Using the National Cancer Institute’s (NCI) Patterns of Care data, we examined treatment provided to childhood neuroblastoma patients newly diagnosed in 2010 and 2011 and registered to one of 14 Surveillance, Epidemiology, and End Results (SEER) cancer registries. Data were re-abstracted from hospital records and treating physicians were contacted to verify the treatment given. Stratifying by the Children’s Oncology Group (COG)’s 3-level (low, intermediate and high) neuroblastoma risk classification system for therapeutic decision-making, gave a snapshot of community-based treatment patterns. Kaplan-Meier survival analyses were also performed. Results: The majority of 250 patients (76%) were enrolled on an open/active clinical trial. All low-risk patients received surgery with/without chemotherapy. The majority of intermediate-risk patients (77%) received chemotherapy regimen that included carboplatin, etoposide, cyclophosphamide and doxorubicin. High-risk patients received extensive, multimodal treatment consisting of chemotherapy, surgery, high dose chemotherapy with stem cell rescue (transplant), radiation, immunotherapy (dinutuximab), and isotretinoin therapy. Cyclophosphamide was the most utilized chemotherapy agent (94%) in high-risk patients. Survival with a maximum follow-up of 48 months, was lowest (68%) for patients diagnosed with high-risk disease. Conclusions: The majority of childhood neuroblastoma patients are registered on a risk-based open/active clinical trial. Variation in modality, systemic agents and sequence of treatment reflects the heterogeneity of therapy for childhood neuroblastoma patients.

Anthropometric and Laboratory Variables Related to Weight Loss-Comparison of Heart Failure Patients with Tumor Patients and Control Population.

Body weight loss is an important feature of heart failure (HF) and tumors. It is related to both reduced survival and adverse reactions to therapy in both of these conditions. The mechanisms of body weight loss in patients with HF and tumors are considered to be similar. Yet, studies comparing those two populations are generally lacking. The aim of this study was to compare anthropometric and laboratory data, related to weight loss, between patients with chronic HF and patients with different tumors as well as control population. Laboratory and anthropometric data on 143 consecutive patients with chronic HF and malignant diseases as well as data for 20 controls were collected. Patients with HF had lower levels of C-reactive protein (CRP) and albumin compared to controls. Anthropometric measurements revealed lower body mass index (BMI), muscle strength, mid-arm circumference, and waist circumference in patients with HF compared to controls. Measurements of biceps, triceps, subscapular, and suprailiac skinfolds were also lower in HF group. Compared to solid tumor group, HF patients had lower levels of CRP and higher levels of hemoglobin. Solid tumor patients had lower values of BMI and subscapular skinfold thickness, as well as higher muscle strength compared to HF group. Finally, compared to patients with solid hematological tumors, HF group had lower levels of albumin, lower muscle strength, as well as lower mid-arm circumference. We found differences in anthropometric and laboratory features, related to weight loss, in patients with HF compared to control population that were expected. On the other hand, observed differences in HF group compared to patients with various tumors could imply different pathophysiological mechanisms of weight loss between those groups. Such data could serve as a cornerstone for studies with larger numbers of patients and deeper pathophysiological insight.

Neoadjuvant chemotherapy in soft tissue sarcomas: latest evidence and clinical implications.

Soft tissue sarcomas are a rare and multifaceted group of solid tumours. Neoadjuvant chemotherapy is increasingly used to limit loss of function after wide surgical excision with the ultimate aim of improving patient survival. Recently, advances in the identification of effective treatment strategies and improvements in patient risk stratification have been reached. A randomized trial demonstrated that neoadjuvant epirubicin and ifosfamide improves survival of patients affected by five high-risk soft tissue sarcoma histologies of trunk and extremities, including undifferentiated pleomorphic sarcoma, myxoid liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumours, and leiomyosarcoma. Selection of patients for these treatments is expected to be improved by the eighth edition of the American Joint Committee on Cancer (AJCC) TNM staging system, as it tailors T-stage categories on primary tumour site and considers a prognostic nomogram for retroperitoneal sarcoma, which also includes soft tissue sarcoma histology and other patient and tumour features not directly included in the TNM staging. Within this framework, this article will present neoadjuvant treatment strategies for high-risk soft tissue sarcoma, emphasizing the most recent advances and discussing the need for further research to improve the effectiveness of neoadjuvant treatments.

Autologous hematopoietic stem cell transplantation following high-dose chemotherapy for nonrhabdomyosarcoma soft tissue sarcomas.

Soft tissue sarcomas (STS) are a highly heterogeneous group of rare malignant solid tumors. Nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) comprise all STS except rhabdomyosarcoma. In people with advanced local or metastatic disease, autologous hematopoietic stem cell transplantation (HSCT) applied after high-dose chemotherapy (HDCT) is a planned rescue therapy for HDCT-related severe hematologic toxicity. The rationale for this update is to determine whether any randomized controlled trials (RCTs) have been conducted and to clarify whether HDCT followed by autologous HSCT has a survival advantage. To assess the efficacy and safety of high-dose chemotherapy (HDCT) followed by autologous hematopoietic stem cell transplantation (HSCT) for all stages of nonrhabdomyosarcoma soft tissue sarcomas (NRSTS) in children and adults. For this update, we revised the search strategy to improve the precision and reduce the number of irrelevant hits. We searched the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 8), PubMed from 2012 to 6 September 2016, and Embase from 2012 to 26 September 2016. We searched online trial registries and congress proceedings from 2012 to 26 September 2016. Terms representing STS and autologous HSCT were required in the title or abstract. We restricted the study design to RCTs. We included studies if at least 80% of participants had a diagnosis listed in any version of the World Health Organization (WHO) classification and classified as malignant. The search included children and adults with no age limits. We used standard methodologic procedures expected by Cochrane. The primary outcomes were overall survival and treatment-related mortality. We identified 1549 records; 85 items from electronic databases, 45 from study registries, and 1419 from congress proceedings. The revised search strategy did not identify any additional RCTs. In the previous version of the review, we identified one RCT comparing HDCT followed by autologous HSCT versus standard-dose chemotherapy (SDCT). The trial randomized 87 participants who were considerably heterogeneous with respect to 19 different tumor entities. The data from 83 participants were available for analysis.In the single included trial, overall survival at three years was 32.7% in the HDCT arm versus 49.4% in the SDCT arm and there was no difference between the treatment groups (hazard ratio (HR) 1.26, 95% confidence interval (CI) 0.70 to 2.29, P = 0.44; 1 study, 83 participants; high quality evidence). In a subgroup of participants who had a complete response before HDCT, overall survival was higher in both treatment groups and overall survival at three years was 42.8% in the HDCT arm versus 83.9% in the SDCT arm and favored the SDCT group (HR 2.92, 95% CI 1.1 to 7.6, P = 0.028; 1 study, 39 participants).In the single included trial, the authors reported one treatment-related leukemia death two years after HDCT. They also evaluated severe adverse events WHO grade 3 to 4 in 22 participants in the HDCT arm and in 51 participants in the SDCT arm. The authors reported 11 events concerning digestive-, infection-, pain-, or asthenia-related toxicity in the HDCT arm and one event in the SDCT arm (moderate quality evidence). The development of secondary neoplasia was not addressed. We judged the study to have an overall unclear risk of bias as three of seven items had unclear and four items had low risk of bias. For GRADE, we judged three items as high quality and three items were not reported. The limited data of a single RCT with an unclear risk of bias and moderate to high quality evidence showed no survival advantage for HDCT. If this treatment is offered it should only be given after careful consideration on an individual person basis and possibly only as part of a well-designed RCT.

Impact of Malignancy Category on Vancomycin Dosage Requirements in Pediatric Oncology Patients

Objectives: To determine the dosage of vancomycin in milligrams/kilogram/day (mg/kg/day) required to achieve a trough value of 10 to 20 micrograms/milliliter (mcg/mL) in pediatric patients with differing types of malignancies. Methods: Retrospective review of pediatric patients with hematologic malignancy, solid tumor, or status post autologous or allogeneic hematopoietic stem cell transplantation (HSCT) receiving at least two doses of intravenous vancomycin with at least one evaluable trough concentration. Primary outcome was the dosage of vancomycin required to achieve first therapeutic trough value. Secondary endpoints included dosage requirement by age, proportion of patients achieving goal, incidence of supratherapeutic trough values and nephrotoxicity. Results: Mean dosage requirements were 72.5 [± 2.3] mg/kg/day among patients with hematologic malignancies, 66.5 [± 3.3] mg/kg/day in patients with solid tumors, and 77.3 [± 4.1] mg/kg/day in HSCT patients (p=0.12). Younger patients required significantly increased daily dosages in order to meet their trough goals in the hematologic malignancy and solid tumor groups (p<0.05). The proportion of patients achieving trough goals was also similar between groups (p=0.5). Supratherapeutic trough values were more common in the solid tumor groups (p<0.05). Nephrotoxicity occurred more frequently in the HSCT group (p<0.05). Conclusion: Vancomycin dosage requirements are similar between pediatric patients with differing categories of malignancies. Patients with solid tumors and HSCT appear to be at higher risk for supratherapeutic trough values, and HSCT patients appear to be at an increased risk for nephrotoxicity.