Embryonal sarcoma of the liver (ESL) is a rare mesenchymal tumor most common in childhood; the optimal treatment approach is uncertain. The clinical features and outcomes of patients with ESL ...enrolled in a Children's Oncology Group (COG) clinical trial that evaluated a risk-based strategy for treating soft tissue sarcomas in patients aged <30 years were evaluated.
This subset analysis included patients with ESL enrolled in COG study ARST0332. Central review of records, pathology, and imaging confirmed the diagnosis, presenting features, and surgery extent and complications. All patients received dose-intensive ifosfamide/doxorubicin chemotherapy, with cycle timing dependent on surgery and radiotherapy. Tumor resection occurred before study entry or after four cycles of chemotherapy; radiotherapy for residual tumor was optional.
Thirty-nine eligible/evaluable patients with ESL were analyzed. All tumors were >10 cm in diameter; four were metastatic. Tumor resection was performed upfront in 23 and delayed in 16. Positive surgical margins (n = 6) and intraoperative tumor rupture (n = 6) occurred only in upfront resections. Eight patients received radiotherapy. Estimated 5-year event-free and overall survival were 79% (95% confidence interval CI, 65%-93%) and 95% (95% CI, 87%-100%), respectively. Positive margins increased the local recurrence risk. One of 13 patients with documented hemorrhagic ascites and/or tumor rupture developed extrahepatic intra-abdominal tumor recurrence.
The treatment strategy used in ARST0332 achieved favorable outcomes for patients with ESL despite a substantial proportion having high-risk disease features. Deferring tumor resection until after neoadjuvant chemotherapy may decrease the risk of intraoperative tumor rupture and improve the likelihood of adequate surgical margins.
Pediatric soft tissue tumors are one of the areas of pediatric pathology that frequently generate consult requests. Evolving classification systems, ancillary testing methods, new treatment options, ...research enrollment opportunities, and tissue archival processes create additional complexity in handling these unique specimens. Pathologists are at the heart of this critical decision-making, balancing responsibilities to consider expediency, accessibility, and cost-effectiveness of ancillary testing during pathologic examination and reporting.
To provide a practical approach to handling pediatric soft tissue tumor specimens, including volume considerations, immunohistochemical staining panel recommendations, genetic and molecular testing approaches, and other processes that impact the quality and efficiency of tumor tissue triage.
The World Health Organization Classification of Soft Tissue and Bone Tumors, 5th edition, other recent literature investigating tissue handling, and the collective clinical experience of the group are used in this manuscript.
Pediatric soft tissue tumors can be difficult to diagnose, and evaluation can be improved by adopting a thoughtful, algorithmic approach to maximize available tissue and minimize time to diagnosis.
Regional lymph node disease (RLND) is a component of the risk-based treatment stratification in rhabdomyosarcoma (RMS). The purpose of this study was to determine the contribution of RLND to ...prognosis for patients with RMS.
Patient characteristics and survival outcomes for patients enrolled onto Intergroup Rhabdomyosarcoma Study IV (N = 898, 1991 to 1997) were evaluated among the following three patient groups: nonmetastatic patients with clinical or pathologic negative nodes (N0, 696 patients); patients with clinical or pathologic positive nodes (N1, 125 patients); and patients with a single site of metastatic disease (77 patients).
Outcomes for patients with nonmetastatic alveolar N0 RMS were significantly better than for patients with N1 RMS (5-year failure-free survival FFS, 73% v 43%, respectively; 5-year overall survival OS, 80% v 46%, respectively; P < .001). Patients with a single site of alveolar metastasis had even worse FFS and OS (23% FFS and OS, P = .01) when compared with patients with N1 RMS; however, the differences was not as large as the differences between patients with N0 RMS and N1 RMS. For embryonal RMS, there was no statistically significant difference in FFS or OS (P = .41 and P = .77, respectively) for patients with N1 versus N0 RMS. Gene array analysis of primary tumor specimens identified that genes associated with the immune system and antigen presentation were significantly increased in N1 versus N0 alveolar RMS.
RLND alters prognosis for alveolar but not embryonal RMS. For patients with N1 disease and alveolar histology, outcomes were more similar to distant metastatic disease rather than local disease. Current data suggest that more aggressive therapy for patients with alveolar N1 RMS may be warranted.
The formative period of the specialty of gynecologic oncology was from 1968 to 1972 and became a board-certified specialty in 1973. During this formation there were no Black physicians participating ...in this process. We chronicle and document the incorporation of the first three board-certified Black physicians in the specialty of gynecologic oncology here for historical purposes.
We highlight the hostile climate experienced by Black physicians before and during the formation of gynecologic oncology, review the acceptance and training of the first three Black physicians in the specialty and recognize their significant contributions to the field.
The biographies and the narrative of these men describe their impact and contribution to medicine. We chronicle the historic presence of the first board-certified Black gynecologic oncologists and pelvic surgeons in the United States.
These three men represent the Black Founding Fathers of gynecologic oncology. Their perseverance in the face of adversity and commitment to excellence have left an indelible impact on the institutions that they developed, the individuals that they trained, and the patients that they served.
•Black Founding Fathers of Gynecologic Oncology.•Historic chronicle of the first three Black fellowship trained board-certified gynecologic oncologist in the U.S.•Development of academic forum in the Ob/Gyn section of the National Medical Association.•Savage Boyce Walton Gynecologic Oncology Honor Society.
This study presents the first messenger RNA (mRNA) therapy for metastatic ovarian cancer and cachexia‐induced muscle wasting based on lipid nanoparticles that deliver follistatin (FST) mRNA ...predominantly to cancer clusters following intraperitoneal administration. The secreted FST protein, endogenously synthesized from delivered mRNA, efficiently reduces elevated activin A levels associated with aggressive ovarian cancer and associated cachexia. By altering the cancer cell phenotype, mRNA treatment prevents malignant ascites, delays cancer progression, induces the formation of solid tumors, and preserves muscle mass in cancer‐bearing mice by inhibiting negative regulators of muscle mass. Finally, mRNA therapy provides synergistic effects in combination with cisplatin, increasing the survival of mice and counteracting muscle atrophy induced by chemotherapy and cancer‐associated cachexia. The treated mice develop few nonadherent tumors that are easily resected from the peritoneum. Clinically, this nanomedicine‐based mRNA therapy can facilitate complete cytoreduction, target resistance, improve resilience during aggressive chemotherapy, and improve survival in advanced ovarian cancer.
Through the suppression of negative regulators of muscle mass and modulation of ovarian cancer cluster morphology, follistatin mRNA lipid nanoparticle treatment prevents malignant ascites, enhances solid tumor form, delays cancer progression, and preserves muscle mass in cancer‐bearing mice. Follistatin mRNA treatment increases mice survival while decreasing chemotherapy‐induced muscular atrophy and cancer‐associated cachexia.
Endometrial cancer is the most commonly diagnosed female genital tract malignancy in the United States of America. Racial disparities surrounding this particular disease have been extensively ...investigated for over 26-years. We sought to determine if research in this area has led to any significant improvements in this disparity.
We performed a rapid systematic review of English language publications on racial disparities in endometrial cancer among African American (AAW) and white American women (WAW), from 1997 to 2023. We looked at trends in incidence and survival; impact of known poor prognostic factors (stage at diagnosis, histological subtypes, grade); co-morbidities; differences in treatment (surgery, radiation and chemotherapy); socioeconomic factors; differences in biological and genetic markers; and policies/declarations.
During the period under review (1997–2023), there was a notable increase in both disease incidence (39%) and mortality (26%) rates for AAW, in comparison to WAW among whom the incidence rates increased by 2% and mortality rates rose, but 9% less than for AAW. It should be noted that the current incidence rate of 29.4% in AAW represent a reversal of what is was 26-years ago, when the incidence rate was 17.8%.
In comparison to WAW, AAW had a higher prevalence of poor prognostic variables, more co-morbidities, lower income levels, less insurance coverage, and were more frequently under treated with surgery, chemotherapy and radiation. To date no actionable molecular/genetic markers have been identified. We were unable to locate any published recommendations or active programs of implementation strategies/policies designed to effectively mitigate the documented racial disparity.
Racial disparities in disease incidence and mortality in endometrial cancer rates between WAW and AAW have widened during a 26-year period of robust research, suggesting that current research alone is not enough to eliminate this disparity. Based on this rapid systematic review we have identified and analyzed the impact of causation variables on this disparity. Additionally, we have made strong and pertinent recommendations for the benefit of mitigating this escalating racial disparity.
•Racial disparities in endometrial cancer between white American and African American continue to widen•Three decades of current research has not lead to the elimination of this disparity•There is a complex intermingling of causation variables negatively affecting survival disparity•Race alone as a social construct is not the cause of this disparity•No biological markers have been identified that are clinically actionable for therapy or explain this disparity
The OncoKids panel is an amplification-based next-generation sequencing assay designed to detect diagnostic, prognostic, and therapeutic markers across the spectrum of pediatric malignancies, ...including leukemias, sarcomas, brain tumors, and embryonal tumors. This panel uses low input amounts of DNA (20 ng) and RNA (20 ng) and is compatible with formalin-fixed, paraffin-embedded and frozen tissue, bone marrow, and peripheral blood. The DNA content of this panel covers the full coding regions of 44 cancer predisposition loci, tumor suppressor genes, and oncogenes; hotspots for mutations in 82 genes; and amplification events in 24 genes. The RNA content includes 1421 targeted gene fusions. We describe the validation of this panel by using a large cohort of 192 unique clinical samples that included a wide range of tumor types and alterations. Robust performance was observed for analytical sensitivity, reproducibility, and limit of detection studies. The results from this study support the use of OncoKids for routine clinical testing of a wide variety of pediatric malignancies.
Abstract
Chute (CS) and exit (ES) scores are common subjective methods used to evaluate temperament in cattle production systems. A pen test, which allows behavior to be observed in a non-restrained ...setting, may also be an effective method to evaluate temperament by allowing more variation among animals to be expressed. The merit of pen scores in assisting producers in evaluating temperament is equivocal. The objectives of this study were to validate the usefulness of a pen score in delineating temperamental cattle and to determine whether these behavioral scores change under repeated and routine management. Over 3 consecutive years, a factorial design of two measurement protocols (frequent F, infrequent IN) and three recording periods was used. The F measurements were collected over 3 consecutive days and IN measurements only on day 1 within a recording period. Each year, 20 mostly Angus commercial Bos taurus heifers were randomly assigned to each protocol. Behavior was measured using a CS, ES, and exit velocity. Body temperature and heart rate also were recorded. A fecal and blood sample were collected and analyzed for levels of various metabolites including glucose concentration and serum cortisol. Following routine handling, each heifers’ response to 30 s of exposure to a human stressor was recorded both individually and in groups of four. An individual (IPS) and group (GPS) pen scores were assigned from 1 (docile) to 6 (aggressive). For all heifers, protocol, event, and their interaction, were compared on the first day of an event. For F heifers, event and day within event were instead used. Body weight was included as a covariate, with sire and year fitted as random effects. Reliability of IPS and GPS were determined using a kappa (K) coefficient. Both IPS and GPS were reliably assigned (K = 0.64 and 0.44 for IPS and GPS, respectively) and positively correlated with body temperature, heart rate, glucose, and serum cortisol (r = 0.28 to 0.37). Furthermore, F heifers acclimated to repeated handling in an individual pen setting (P < 0.05) while acclimation to handling within groups was not evident (P > 0.14). IPS provides a reliable evaluation of temperament in a non-restrained setting that is indicative of an animal’s response to stress and may be useful when attempting to make phenotypic selection decisions. However, temperamental heifers became calmer with repeated gentle handling.
Lay Summary
Chute and exit scores are common subjective methods used to evaluate temperament in cattle production systems. A pen test, which allows behavior to be observed in a non-restrained setting, may also be an effective method to evaluate temperament by allowing more variation among animals to be expressed. However, the merit of pen scores in assisting producers in evaluating temperament has yet to be discerned. Therefore, the objectives of this study were to validate the usefulness of pen scores in delineating temperamental cattle and to determine whether these behavioral scores change under repeated and routine management. Pen scores collected on heifers either individually or as a group could be assigned reliably and were indicative of an animal’s response to stress during normal handling practices. Temperamental heifers, when handled more frequently, acclimated to repeated handling in an individual pen setting but not in a group. Therefore, regardless of method, when cattle are excitable during their first handling experience, more than one observation of temperament may be beneficial before assessing temperament.
Pen scores collected on heifers either individually or as a group can be reliably assigned and are indicative of an animal’s response to stress during normal handling practices.
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