Clinical Impact of Nutritional Status and Sarcopenia in Pediatric Patients with Bone and Soft Tissue Sarcomas: A Pilot Retrospective Study (SarcoPed).

BACKGROUND: We evaluated nutritional and sarcopenia status and their clinical impact in pediatric patients affected by bone and soft tissue sarcomas. METHODS: Body mass index (BMI), prognostic nutritional index (PNI), and total psoas muscle area (tPMA) at diagnosis and after 12 months were analyzed. tPMA was measured from single cross-sectional computed tomography (CT) images at L4-L5. Age-specific and sex-specific tPMA Z-scores were retrieved from an online calculator. RESULTS: A total of 21 patients were identified between February 2013 and December 2018. Twelve patients (57.1%) experienced sarcopenia at diagnosis, although not statistically associated with overall survival (OS) (p = 0.09). BMI Z-score, PNI, and tPMA Z-score significantly decreased between diagnosis and after 12 months of treatment (p < 0.05). Univariate analysis showed significant associations between poor OS and the presence of metastasis (p = 0.008), the absence of surgery (p = 0.005), PNI decrease (p = 0.027), and the reduction in tPMA > 25% (p = 0.042) over the 12 months. CONCLUSIONS: Sarcopenia affects more than half of the patients at diagnosis. Decreased PNI during 12 months of treatment has significant predictive value for OS. The role of tPMA derived from CT scan among pediatric patients with sarcoma should be investigated in further prospective and larger studies.

Successful pregnancy after limb-sparing hemipelvectomy for Ewing sarcoma: Case report and literature review.

OBJECTIVE: We present a case of successful pregnancy in a patient who underwent limb-sparing hemipelvectomy combined with multi-agent chemotherapy and radiotherapy for Ewing sarcoma. CASE REPORT: A 17-year-old girl was diagnosed with Ewing sarcoma of the left pelvis at the age of 17 and received limb-sparing hemipelvectomy combined with multi-agent chemotherapy and radiotherapy. The patient received oral contraceptives as hormone replacement therapy after completion of treatment. A normal menstruation cycle restored after the withdrawal of oral contraceptives. The patient spontaneously conceived at the age of 25. The patient complained of difficulty walking due to pelvic distortion during pregnancy and delivered a healthy neonate at term by cesarean section. CONCLUSION: Successful pregnancy and delivery can be achieved after limb-sparing hemipelvectomy combined with chemotherapy and radiotherapy for Ewing sarcoma. Our report provides important information on perinatal management, given the low incidence of pregnancy following treatment of Ewing sarcoma in the pelvis.

Metastatic pulmonary dissemination as differential diagnosis of COVID-19 disease.

A 13-year-old boy presented to hospital with 3-day self-limited fever, followed by dry cough, persistent asthenia and impaired general condition of 2 weeks' duration. Blood analyses showed a severe inflammatory status and chest X-ray images were consistent with bilateral COVID-19 pneumonia. He developed an acute respiratory failure that required paediatric intensive care admission and non-invasive ventilation. A targeted COVID-19 treatment was initiated with hydroxicloroquine, corticosteroids, enoxaparine and a single dose of tocilizumab. Repeated serological tests and real-time reverse transcription PCR for SARS-CoV-2 were negative. Other infectious pathogens were also ruled out. Thoracic high resolution CT showed an intense bilateral pulmonary dissemination with lytic vertebral bone lesions. After diagnostic investigations, Ewing's sarcoma with metastatic pulmonary dissemination was diagnosed. Nowadays, in the context of SARS-CoV-2 community pandemic, we cannot forget that COVID-19 clinical presentation is not specific and other entities can mimic its clinical features.

Identifying bone sarcoma survivors facing psychosocial challenges. A study of trajectories following treatment.

OBJECTIVE: Bone sarcoma survivors face a number of physical and psychosocial challenges in relation to the late effects they experience following treatment. The present study aimed to identify and explore the different trajectories that bone sarcoma survivors might navigate during follow-up. METHODS: In-depth and semi-structured interviews were conducted, and an inductive thematic analysis was performed. RESULTS: When they were interviewed three to ten years after the primary diagnosis, the eighteen bone cancer survivors were found to be in three different rehabilitation phases that followed fairly distinct trajectories, namely, back to normal, a new normal and still struggling. Only three participants felt that they had returned to a life that was quite similar to the one they had lived prior to having cancer. Fifteen participants considered their lives and their bodies to be significantly altered. CONCLUSION: Sarcoma survivors who undergo life-changing treatment and return to very different lives than they had before should be identified by healthcare professionals and guided through this demanding phase to better cope with their new living conditions. Information on and tailored guidance related to psychosocial challenges may be of particular importance. Active focus on reorientation, as well as possibilities for growth, seems to be important.

Use of Vascularized Fibular Free Flap in the Reconstruction of the Femur in Pediatric and Adolescent Bone Sarcomas: Complications and Functional Outcome.

BACKGROUND: Most reports on skeletal reconstruction using vascularized fibular free flap include patients with varying age groups and anatomic locations. This study has limited the inclusion criteria to pediatric and adolescent patients diagnosed with bone sarcoma of the femoral shaft. METHODS: Forty-one patients, diagnosed with a malignant bone tumor of the femoral shaft (21 Ewing's sarcomas and 20 osteosarcomas), were locally treated by joint sparing wide resection and reconstruction using a vascularized fibular free flap. All clinical and radiographic data were reviewed for graft healing and hypertrophy as well as oncologic and functional outcome. RESULTS: The mean follow-up period was 48.7 months (12-104 months). The mean age at presentation was 10.3 years (5-17 years). The average length of the resected femoral shaft was 19.2 cm (15-24 cm) and the average length of the harvested fibula was 17.4 cm (15-21 cm). The mean time to union was 4.8 months (1-6 months) and the mean hypertrophy index was 78% (15.5-184%). Complications included 12 fractures (33.3%), 5 non-unions (13.8%), and 5 failures of graft hypertrophy (13.8%). At the latest clinical evaluation, the mean MSTS score was 81% (56-100%) and the mean limb length inequality was 4.75 cm (3-11 cm). CONCLUSION: Despite the high functional demand and deleterious effect of chemotherapy on bone healing, reconstruction of the femur by vascularized fibular free flap in pediatric bone sarcomas can lead to a good functional outcome. Complications, such as fracture and non-union, can be successfully treated by revision of fixation and autologous iliac crest grafting. LEVEL OF EVIDENCE: IV.

Microsurgical reconstruction with vascularized fibula and massive bone allograft for bone tumors.

INTRODUCTION: Combining massive bone allograft and vascularized fibula in intercalary reconstruction following resection of bone tumors represents a complex reconstructive procedure that requires specialists in microvascular surgery as well as orthopedic surgery. The purpose of our study was to examine the outcomes using this surgical technique in patients with bone tumors in terms of oncologic results, complications related to surgery, Musculoskeletal Tumor Society (MSTS) scores and duration of surgery. MATERIALS AND METHODS: We analyzed 81 patients with femoral or tibial sarcomas who underwent intercalary resection and microsurgical reconstruction with massive bone allograft and vascularized fibula. There were 56 boys and 25 girls with a mean age of 13.4 years at the time of surgery. The patients' medical records were reviewed for clinical and functional outcomes as well as postoperative complications. The study group was comprised of 33 patients who underwent reconstruction of the femur with massive bone allograft and free vascularized fibula and 48 patients who underwent reconstruction of the tibia with massive bone allograft and free or pedicle vascularized fibula. The mean length of resection was 15.9 cm (8-31 cm). The functional evaluation of the patients was done at the end of the follow-up using MSTS score for the lower limb. All patients had at least a 2-year follow-up. RESULTS: The overall limb salvage rate was 94%, although many patients required re-operation after the procedure. Complications occurred in 24 patients, 18 of which underwent additional surgical procedures. They included fractures of the massive bone allograft-vascularized fibula construct with or without implant failure (19) and deep infection (5). After surgical or conservative treatment, all the fractures successfully healed. The overall MSTS functional score was good to excellent in 91% of patients. CONCLUSIONS: The combination of massive bone allograft and vascularized fibula seems to be a reasonable option for reconstruction of diaphyseal defects following intercalary resection of bone tumors. Although there was a high rate of complications and therefore re-operations, the biology of vascularized fibula was able to save the reconstruction in most of the cases that had complications.

Clinical Features and Prognostic Factors in Elderly Ewing Sarcoma Patients.

BACKGROUND Elderly patients with Ewing sarcoma have a very poor prognosis, and treatment remains a challenge. However, the outcomes and potential prognostic factors of elderly Ewing sarcoma patients are rarely documented. Therefore, we investigated the prognosis of this special cohort and determine independent prognostic factors. MATERIAL AND METHODS A cohort of Ewing sarcoma patients aged over 40 years from 1973 to 2015 was identified from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method and a Cox proportional hazard regression model were used for the prognostic analysis. RESULTS A total of 162 patients were included with a mean age of 53 years. The 5-year overall survival (OS) and cancer-specific survival (CSS) rates of the entire group were 43.7% and 47.9%, respectively. The sex, location, tumor size, and radiation treatment had no effect on survival outcomes on univariate analysis. Tumor stage, surgery, and chemotherapy were significant indicators of both OS and CSS on multivariable analysis. CONCLUSIONS Surgery in combination with chemotherapy had a significant survival benefit in elderly Ewing sarcoma patients and should be recommended.

Imaging features of Ewing's sarcoma: Special reference to uncommon features and rare sites of presentation.

CONTEXT: Ewing's sarcoma (EWS) commonly involves long bones with a permeative pattern of bone destruction and aggressive interrupted periosteal new bone formation. However, radiological features show wide variation and some presentations are uncommon, leading to diagnostic confusion. This study is aimed at studying the imaging features of proven EWS and highlight the uncommon features and rare sites of presentation. MATERIALS AND METHODS: The imaging findings of 100 consecutive histopathologically proven EWS were analyzed retrospectively. All uncommon presentations with respect to age and site and morphology of lesion were observed. RESULTS: Most of the patients were below 20 years of age and 8% were younger than 5 years. Other than long bones, ribs, and pelvis, other sites considered to be rare and were noted in 25%. Extraosseous site involvement was 11%. Uncommon features included epiphyseal involvement (4%), sclerosis (4%), expansion of bone (8%), sunray spiculation (10%), calcification in soft tissue (8%), saucerization (4%), pathological fracture (5%), fluid-fluid level (2%), vertebra plana (2%), and lesion crossing the joint (13%). CONCLUSIONS: The uncommon observations included incidence in children <5 years (8%) and occurrence in craniofacial bones, spine, scapula, and clavicles and in extraosseous sites such as retroperitoneum, adrenals, or extremity. Uncommon findings included epiphyseal involvement, sclerosis, saucerization, calcification in soft tissue component, and pathological fracture and lesion crossing the joint.

Ewing sarcoma.

Ewing sarcoma is the second most frequent bone tumour of childhood and adolescence that can also arise in soft tissue. Ewing sarcoma is a highly aggressive cancer, with a survival of 70-80% for patients with standard-risk and localized disease and ~30% for those with metastatic disease. Treatment comprises local surgery, radiotherapy and polychemotherapy, which are associated with acute and chronic adverse effects that may compromise quality of life in survivors. Histologically, Ewing sarcomas are composed of small round cells expressing high levels of CD99. Genetically, they are characterized by balanced chromosomal translocations in which a member of the FET gene family is fused with an ETS transcription factor, with the most common fusion being EWSR1-FLI1 (85% of cases). Ewing sarcoma breakpoint region 1 protein (EWSR1)-Friend leukaemia integration 1 transcription factor (FLI1) is a tumour-specific chimeric transcription factor (EWSR1-FLI1) with neomorphic effects that massively rewires the transcriptome. Additionally, EWSR1-FLI1 reprogrammes the epigenome by inducing de novo enhancers at GGAA microsatellites and by altering the state of gene regulatory elements, creating a unique epigenetic signature. Additional mutations at diagnosis are rare and mainly involve STAG2, TP53 and CDKN2A deletions. Emerging studies on the molecular mechanisms of Ewing sarcoma hold promise for improvements in early detection, disease monitoring, lower treatment-related toxicity, overall survival and quality of life.

Quality of Survivorship in a Rare Disease: Clinicofunctional Outcome and Physical Activity in an Observational Cohort Study of 618 Long-Term Survivors of Ewing Sarcoma.

Purpose Significantly improved survival rates in patients with Ewing sarcoma have raised interest in accessing the quality of long-term survivorship. In this study, subjective and objective measurement tools, preclassified as physical or mental scores, were used to assess clinicofunctional outcome and physical activity after intensive bone tumor treatment. Methods Long-term outcome of 618 survivors from consecutive Ewing sarcoma trials was assessed by the Toronto Extremity Salvage Score, Short-Form Health Survey (SF-36), Brief Symptom Inventory (BSI), and Rosenberg Self-Esteem Scale questionnaires and by the accelerometric StepWatch 3 Activity Monitor. Prospective measurements were correlated retrospectively with standardized primary trial data. Results were compared with 316 nonrandom healthy peers by using effect sizes ( d). Median observation time was 12.9 years from primary diagnosis (range, 3.7 to 31.2 years). Results Absolute subjective scores were moderate to good for survivors. Compared with control subjects, unfavorable outcome was shown on physical Toronto Extremity Salvage Score, SF-36 Physical Component Summary, and BSI-Somatization scales (| d| ≥ 0.50; P < .01), in contrast to SF-36 Mental Component Summary, BSI-Anxiety, BSI-Depression, and Rosenberg Self-Esteem Scale mental scales (| d| ≤ 0.31). Survivors were less active than control subjects, as demonstrated by a step count difference of 1,742 steps per day ( d = -0.43; P < .01); however, on average, the recommended level for an active lifestyle was achieved (≥ 10,000 steps). Location of pelvic tumor was the major inferior disease-specific prognostic factor in physical scores ( P < .01), whereas nondisease-specific inferior factors in questionnaires were older age and female sex ( P < .01). Conclusion Survivors of Ewing sarcoma apparently returned to a normal life with minor limitations. Observed reductions in physical scores should be a focus in future research to optimize treatment strategies to reduce a negative impact on the quality of survivorship.

Sarcoma survivors' perspectives on their body image and functional quality of life post-resection/limb salvage surgery.

Sarcomas often occur in patients' extremities and treatment typically involves bone resection/limb salvage surgery. Such treatments leave survivors with physical disfigurements, functional disabilities, and/or emotional traumas. Our post-surgery psychological intervention investigated how these experiences impinge on sarcoma survivors' lives. Twenty-three survivors aged 19-60 years (M = 36 years) participated in a tri-disciplinary (rehabilitative exercise, plastic surgery and psychological) intervention. Of these, 17 participated in psychodynamic counselling, 10 completed a mental-health questionnaire and seven kept a reflective journal. An exemplar case study research design was employed and data were subjected to interpretative phenomenological analysis. The findings reveal that survivors typically experience a number of body image issues and mobility difficulties, which they are reluctant to share with their oncologist in case they are viewed as being ungrateful or vain. In instances where such issues remain unaddressed, then sarcoma survivors have a tendency to adopt avoidant coping strategies and social isolation practices. These practices negatively impact on their mental health and functional quality of life. Hence, it is suggested that a short three part (body image, mobility, and coping strategy) screen be devised and used at all sarcoma 2-year follow-up assessment consults to identify which survivors are in need of psychological assistance.

Relationship between bone adaptation and in-vivo mechanical stimulus in biological reconstructions after bone tumor: A biomechanical modeling analysis.

BACKGROUND: Biomechanical interpretations of bone adaptation in biological reconstructions following bone tumors would be crucial for orthopedic oncologists, particularly if based on quantitative observations. This would help plan for surgical treatments, rehabilitative programs and communication with the patients. We aimed to analyze the biomechanical adaptation of a femoral reconstruction after Ewing sarcoma according to an increasingly-used surgical technique, and to relate in-progress bone resorption to the mechanical stimulus induced by different motor activities. METHODS: We created a multiscale musculoskeletal and finite element model from CT scans and motion analysis data at a 76-month follow-up of a patient, to analyze muscle and joint loads, and to compare the mechanical competence of the reconstructed bone with the contralateral limb, in the current real condition and in a possible revision surgery that removed proximal screws. FINDINGS: Our results showed strategies of muscle coordination that led to differences in joint loads between limbs more marked in more demanding motor activities, and generally larger in the contralateral limb. The operated femur presented a markedly low ratio of physiological strain due to load-sharing with the metal implant, particularly in the lateral aspect. The possible revision surgery would help restore a physiological strain configuration, while the safety of the reconstruction would not be threatened. INTERPRETATION: We suggest that bone resorption is related to load-sharing and to the internal forces exerted during movement, and the mechanical stimulus should be improved by adopting modifications in the surgical treatment and by promoting physical therapy aimed at specific muscle strengthening.

The Diagnosis of Iliac Bone Destruction in Children: 22 Cases from Two Centres.

Iliac bone destruction in children is uncommon and presents various imaging features. Correct diagnosis based on clinical and imaging features is difficult. This research aimed to retrospectively explore the clinical features, imaging, and histopathological diagnosis of children with iliac bone destruction. A total of 22 children with iliac bone destruction were enrolled in this retrospective analysis from two children's hospitals during July 2007 to April 2015. Clinical features, imaging, and histopathological findings were analysed. The mode of iliac bone destruction, lesion structure, and the relationship between the range of soft tissue mass and cortical destruction were determined based on imaging data. The data were analysed using descriptive methods. Of the iliac bone destruction cases, eight cases were neuroblastoma iliac bone metastasis, seven cases were bone eosinophilic granuloma, two cases were Ewing's sarcoma, two cases were osteomyelitis, one case was bone cyst, one case was bone fibrous dysplasia, and one case was non-Hodgkin's lymphoma. Iliac bone destruction varies widely in children. Metastatic neuroblastoma and eosinophilic granuloma are the most commonly involved childhood tumours.

Do patients with ewing's sarcoma continue with sports activities after limb salvage surgery of the lower extremity?

BACKGROUND: Limb salvage surgery has evolved to become the standard method of treating sarcomas of the extremities with acceptable oncologic results. However, little information exists relative to the activity level or ability to participate in sports after tumor reconstructions. QUESTIONS/PURPOSES: The aims of the study were to answer the following questions: (1) Which sports activity levels and what types of sports can be expected in the long term after tumor reconstruction? (2) Which frequency durations are patients with Ewing's sarcoma able to perform in long-term followup after local control? (3) Do surgical complications affect sports activity level? METHODS: Thirty patients (13 females, 17 males; mean age, 18 ± 8 years; range, 2-36 years at diagnosis; mean followup 16 ± 6 years [minimum, 5 years]) were included. Tumors were located in the pelvis, femur, tibia, and fibula. Surgical procedures included surgical resections alone (n = 8), surgical resection with biological reconstruction (n = 9), or endoprosthetic reconstruction (n = 13). We assessed UCLA sports activity levels, kinds of sports as well as the frequency per week and the duration of each training unit at long term (minimum followup, 5 years). RESULTS: In long-term followup 83% patients (25 of 30) were performing athletic activity regularly. The hours/week of sports depended on type of surgery and were highest after resections in the pelvis and femur (5.8) and were lowest after megaprosthetic reconstruction of the pelvis (1.0). Patients undergoing biologic reconstructions were able to perform high-impact sports. UCLA sports activity levels were high after joint-preserving vascularized fibula for tibia reconstruction (7.4) and after megaprosthetic reconstruction of the lower extremity (6.3-6.4) and were low after tumors located in the fibula (4.2). Complications during followup did not significantly influence sports activity in long-term survivors. CONCLUSIONS: Long-term survivors can achieve high levels of sports activity in many instances. Tumor sites are associated with the postoperative sports activity levels. This information can help surgeons counsel patients in terms of athletic expectations after limb salvage reconstruction for patients with Ewing's sarcoma. LEVEL OF EVIDENCE: Level III, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Ewing sarcoma inhibition by disruption of EWSR1-FLI1 transcriptional activity and reactivation of p53.

Translocations involving ETS-transcription factors, most commonly leading to the EWSR1-FLI1 fusion protein, are the hallmark of Ewing sarcoma. Despite knowledge of this driving molecular event, an effective therapeutic strategy is lacking. To test potential treatment regimes, we established a novel Ewing sarcoma zebrafish engraftment model allowing time-effective, dynamic quantification of Ewing sarcoma progression and tumour burden in vivo, applicable for screening of single and combined compounds. In Ewing sarcoma the tumour-suppressor gene TP53 is commonly found to be wild-type, thus providing an attractive target for treatment. Here, we study TP53 wild-type (EW7, CADO-ES1 and TC32) and TP53-deleted (SK-N-MC) Ewing sarcoma cell lines to investigate the potentiating effect of p53 reactivation by Nutlin-3 on treatment with YK-4-279 to block transcriptional activity of EWSR1-FLI1 protein. Blocking EWSR1-FLI1 transcriptional activity reduced Ewing sarcoma tumour cell burden irrespective of TP53 status. We show that simultaneous YK-4-279 treatment with Nutlin-3 to stabilize p53 resulted in an additive inhibition of TP53 wild-type Ewing sarcoma cell burden, whilst not affecting TP53-deleted Ewing sarcoma cells. Improved inhibition of proliferation and migration by combinatorial treatment was confirmed in vivo by zebrafish engraftments. Mechanistically, both compounds together additively induced apoptosis of tumour cells in vivo by engaging distinct pathways. We propose reactivation of the p53 pathway in combination with complementary targeted therapy by EWSR1-FLI1 transcriptional activity disruption as a valuable strategy against p53 wild-type Ewing sarcoma.

Paley's multiplier method does not accurately predict adult height in children with bone sarcoma.

BACKGROUND: The majority of patients with osteosarcoma and Ewing's sarcoma are diagnosed before skeletal maturity. Paley's multiplier is used for height prediction in healthy children, and has been suggested as a method to make growth predictions for children with osteosarcoma and Ewing's sarcoma when considering limb salvage options. To our knowledge, no evaluation of this method in this particular patient group has been performed, but a temporary growth deficit has been observed in children undergoing chemotherapy. QUESTIONS/PURPOSES: We asked whether (1) Paley's formula reliably predicts growth in children who received polychemotherapy; (2) chemotherapy impairs growth velocity; and (3) final adult height is impaired in these patients. METHODS: Retrospectively, data for 94 patients with osteosarcoma and Ewing's sarcoma were retrieved from databases of two sarcoma centers. Onset before 14 years of age in girls and 16 years in boys and a minimum followup until 18 years were required (mean, 67 months; range, 31-124 months) criteria. Exclusion criteria were the intake of growth hormones or no chemotherapy. Thirty-three patients (35%) fulfilled all inclusion criteria. Predicted adult heights were compared with actual adult height. The development of a growth deficit was evaluated for 23 children (without chemotherapy for recurrence) using age- and gender-specific standard deviation scores for height (WHO Z-scores). RESULTS: Height prediction using Paley's method showed a high percentage of false predictions (outside ± 1 SD, 70%; outside ± 2 SD, 61%). On average, the mean total height of the patients was overestimated (2.3 cm). The median absolute error of prediction was 5.0 cm (range, -17 to 8). Patients with osteosarcoma and Ewing's sarcoma showed a significant growth impairment during polychemotherapy. A catchup phase in growth before skeletal maturity was observed in patients with osteosarcoma but not with Ewing's sarcoma. CONCLUSIONS: Owing to its lack of reliability in this patient group, methods other than Paley's should be evaluated to predict adult height. Although limited by a small number of patients, our study results indicate a decreased adult height in patients with bone sarcoma after chemotherapy. LEVEL OF EVIDENCE: Level III, therapeutic study. See the Instructions for Authors for complete description of levels of evidence.

Modeling Ewing sarcoma tumors in vitro with 3D scaffolds.

The pronounced biological influence of the tumor microenvironment on cancer progression and metastasis has gained increased recognition over the past decade, yet most preclinical antineoplastic drug testing is still reliant on conventional 2D cell culture systems. Although monolayer cultures recapitulate some of the phenotypic traits observed clinically, they are limited in their ability to model the full range of microenvironmental cues, such as ones elicited by 3D cell-cell and cell-extracellular matrix interactions. To address these shortcomings, we established an ex vivo 3D Ewing sarcoma model that closely mimics the morphology, growth kinetics, and protein expression profile of human tumors. We observed that Ewing sarcoma cells cultured in porous 3D electrospun poly(ε-caprolactone) scaffolds not only were more resistant to traditional cytotoxic drugs than were cells in 2D monolayer culture but also exhibited remarkable differences in the expression pattern of the insulin-like growth factor-1 receptor/mammalian target of rapamycin pathway. This 3D model of the bone microenvironment may have broad applicability for mechanistic studies of bone sarcomas and exhibits the potential to augment preclinical evaluation of antineoplastic drug candidates for these malignancies.