Predictors of recurrence and death for UCS and OCS include poorly differentiated epithelial or serous histology, rhabdomyosarcomatous components, advanced stage, Black race, older age, lymphovascular space invasion, and a history of cancer.This study was sized to assess inferiority of PC to PI in subgroups defined by self-reported race or age. We note several important differences in the two regimens investigated in the trial. First, PI requires a 3-day infusion, whereas PC can be delivered in 1 day. Second, PI requires growth factor support and has complex dosing requirements. Finally, PI likely costs considerably more than PC, although we did not assess cost in this study. In this study, patients in the PI arm were more likely than those in the PC arm to have central neurotoxicity, despite the eligibility requirement of serum albumin $ 3.0 g/dL. In other studies, between 5% and 20% of patients receiving ifosfamide have had central nervous system toxicity, including mild confusion, somnolence, seizure, coma, and death, although most events resolved with appropriate therapy.Central nervous system toxicity has been a major deterrent to ifosfamide use in gynecologic malignancies and has hampered development of ifosfamide-containing drug combinations. Although paclitaxel causes predictable peripheral neurotoxicity, several clinical management optionscan be used to decrease the risk of grade 3 or worse neurotoxicity. In this study,vertical grow shelf dose reductions and dose holds were used to manage peripheral neurotoxicity.
Given that paclitaxel was included in both arms of the study, it is not surprising that no significant interarm differences were seen in quality-of-life assessments of neurotoxicity administered at four time points. The utility of radiation for UCS, especially for early-stage UCS, is unclear. In this study, 13% of the entire cohort received previous pelvic radiation therapy, including 10% of stage I, 15% of stage II, 13% of stage III, 4% of stage IV, and 45% of recurrent disease patients. These rates are somewhat lower than older published data but may reflect recent trends in omitting radiation therapy for these patients in response to data from several studies. For example, GOG 150 noted no statistically significant difference in survival or recurrence rates among patients with UCS who received chemotherapy versus whole abdominal radiation.In European Organisation for Research and Treatment of Cancer protocol 55874, which started in the 1980s and took 13 years to accrue, 91 of 224 patients had UCS. Among the patients with UCS, those in the pelvic radiotherapy arm had fewer local recurrences than those in the observation arm but no statistically significant differences in PFS or OS.In both these trials, relapse tended to occur outside the radiated field or in areas with decreased dose of radiation, compelling many gynecologic oncologists to combine radiation and chemotherapy. Our understanding of carcinosarcoma biology has improved recently. For example, we now know that expression of epithelial-mesenchymal transition–related genes and DNA methylation changes underly the sarcoma differentiation. In addition, like the more common endometrial carcinomas, UCSs can be classified into four molecular subtypes: polymerase epsilon -mutated, microsatellite instability, copy number high, and copy number low.
These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathologic features, including patient outcomes.A predominance of copy number high subtype may explain the aggressive behavior and poor prognosis of UCS. Some differences are noted among the two major UCS molecular characterization studies. Although 81.3% of specimens in The Cancer Genome Atlas contained an epithelial component , 85% of specimens in the Japanese Foundation for Cancer Research were endometrioid. Thus, the histologic appearance of the epithelial component may be important to consider when evaluating treatment decisions. For example, de-escalating treatment of POLE-mutated tumors, using immunotherapy to treat mismatch repair–deficient tumors, and decreasing radiation and escalating chemotherapy to treat human epidermal growth factor receptor 2 –positive tumors are options that can be explored in clinical trial designs. A potentially important target in UCS is HER2 overexpression. Rottman et al found that 16% of 80 gynecologic carcinosarcoma specimens were HER2-positive, similar to the frequency of HER2 expression in endometrial serous carcinomas. Importantly, heterogeneity of HER2 protein expression was observed in 38% of HER2-positive tumors, and a lateral or basolateral membranous staining pattern was common.In a randomized phase II trial, PC plus trastuzumab improved PFS and OS for patients with HER2- positive uterine serous carcinoma.Future studies should assess the utility of this approach in patients with UCS, especially given our findings that PC is an effective therapy for these patients. In conclusion, these results establish a new standard regimen–PC—for women with UCS of all stages and especially for stage III patients.
Toxicity was as predicted and manageable. Identifying and targeting the molecular aberrations in these tumors should lead to further improvements in treatment.Youth in contact with and impacted by the juvenile justice and child welfare systems have high rates of substance use and mental health needs but experience significant disparities in behavioral health services access and engagement relative to youth who are not system-impacted. Among youth at first juvenile court contact , 50% endorse cannabis use and 30% report clinically significant mental health needs.Of the 50% not using cannabis at first contact, 18% initiate cannabis use within the subsequent 12 months.Experiencing multiple adverse childhood experiences , such as parental incarceration, domestic violence exposure, and abuse, is also common by first system contact, and abuse ACEs predict alcohol use and post traumatic stress symptoms 12 months after initial court contact.Yet surprisingly, only 8–16% of youth with legal system contact receive behavioral health services.Factors associated with disparities in service access are complex and include individual, family,neighborhood,and structural barriers associated with racism, poverty, and other macro-level influences.For example, a national survey of juvenile justice community supervision agencies and associated behavioral health provider agencies found that 33% of these systems provide youth substance use prevention services;this is a staggeringly low proportion of services availability relative to need. Even when behavioral health needs are identified, other barriers prevent youth from finding, accessing, and engaging in services. One significant barrier stems from siloed serving systems, which hampers the necessary cross-system collaboration that can improve youth access to community based care.For example, the juvenile dependency court legally oversees the care of all foster care youth. It is responsible for the safety, health, and well-being of these youth in conjunction with multiple stakeholders in numerous systems . Implementation of local change teams and development of cross-system collaborative tools are examples of promising, empirically supported approaches to increasing access to behavioral health services for system-impacted youth and families. Technological advances also hold promise to support increased behavioral health services access; yet, there has been minimal empirical investigation of the use of technology for this purpose and this population of youth, at any level.In 2020, the Youth Justice and Family Well-Being Technology Collaborative was formed to identify and resolve juvenile justice and child welfare system-level barriers to youth behavioral healthcare services access and utilization, specifically using technology. There are three goals of this paper: first, to describe the development, guiding frameworks, and implementation of the JTC model and approach; second, to outline the JTC composition and logistical processes; and third, to present preliminary descriptive outcomes, lessons learned, and suggest next steps for the fields of public health and juvenile justice to consider for cross-system collaborative approaches to advance behavioral health equity through technology for system-impacted youth.Developed by the National Frontier and Rural Addiction Technology and Transfer Center, the TCAT was designed to assist behavioral health organizations to assess their readiness to adopt telehealth technology to increase behavioral health services access. The TCAT highlights six domains that require assessment of their interplay to identify organizational capacity building needs and to develop a Capacity Strengthening Plan to successfully use telehealth technology. The TCAT can also be used to monitor and evaluate the impact of organizational capacity building over time. JTC stakeholders broadened the application of the TCAT framework to incorporate any technology-based interventions and not just telehealth and expand TCAT data collection to other systems beyond behavioral health to examine technology services readiness and capacity within and across multiple JTC systems and organizations .
A TCAT Capacity Strengthening Plan is dynamic and intended to be iteratively revised according to plan progress. The templated plan includes identified TCAT domain and domain subcomponent gaps , listing internal and external resources needed to address the gap, specific planned actions to close the gap, priority determination ,vertical farming supplies assigning stakeholder responsibility for planned actions, and result description.Based on initial meetings guided by the Cascade and TCAT frameworks, the JTC formed subcommittees to allow for simultaneous progress on multiple projects. Subcommittees aligned with key “stuck” points in the Cascade . The JTC also identified a need for a Data Gathering/Sharing subcommittee to support the development and implementation of data-driven approaches to address identified gaps. Below are two examples of subcommittee identified gaps and associated capacity strengthening plans. The Initial Access subcommittee focuses on the TCAT domain of Workforce Capacity and aims to use technology to build clinical workforce capacity. Stakeholders identified the lack of community based child mental health providers with empirically supported substance use intervention training as a workforce gap to address. As part of their Capacity Strengthening Plan, the group is leveraging an existing tele-mentoring model at the University of California, San Francisco to provide ongoing telehealth training and case consultation on adolescent substance use assessment and intervention to behavioral health providers serving system-impacted youth; ECHO is an internationally implemented learning, mentoring, and peer support model to improve health outcomes of under served populations.The Initial Access subcommittee co-developed an ECHO curriculum on trauma-responsive adolescent substance use assessment and intervention that has been successfully implemented with child behavioral health providers in Northern California who serve system-impacted youth. Available data regarding youth and family technology access was identified as a gap particularly because personnel continue to encounter barriers to technology access for youth and families under probation supervision. The Data Gathering/Sharing subcommittee developed a two-question screener to assess at intake to the county juvenile justice system, whether each youth had access to a technology device and internet access. Stakeholders wanted to develop standardized items that would be incorporated into each juvenile legal system’s intake procedures so that courts, probation, public defender, and district attorney could systematically advocate for youth technology access, as needed. The Capacity Strengthening Plan also includes working closely with juvenile legal stakeholders to allow other system stakeholders access to these data so that they may collaborate in reducing barriers to technology access for individual youth and families in need.The TCAT is a 68-item self-report measure designed for stakeholders to plan, design, and monitor implementation of telehealth technology services.The six TCAT domains and their sub-components include organizational readiness , technology , regulatory and policy , financing and reimbursement , clinical , and workforce . Response options are “Don’t Know/Not Applicable” , “No, never considered” , “No, but have considered” , “Yes, in progress , “Yes, nearly completed , and “Yes, in place” for each item. Mean scores were calculated within each of the six domains. After presenting aggregated first time point results to the JTC, stakeholders expressed that it would be helpful to have distinct response options for “Don’t Know” and “Not Applicable”; the TCAT was revised to split into two response options for time points two and three such that “Don’t Know” was assigned a and “Not Applicable” was considered missing data. Response rates varied from 50.0 to 69.2% of stakeholders at any given time point.Quantitative data were analyzed using SPSS 27.Mean scores were calculated for all six domains and then stratified by system. Qualitative data were analyzed via atlasTI.7 in Windows using Inductive Thematic Analysis methods.The initial code book was derived from the six TCAT domains related to incorporating technology into practice and was further refned based on emergent themes identified by two research team members through preliminary coding of two de-identified meeting notes. This process was repeated until all redundancies were removed and potential themes were identified. The two members of the research team then consulted with two qualitative experts on the research team who made minor revisions and provided feedback on the preliminary code book. Regular meetings between these two researchers and the qualitative experts were held to reach consensus and to develop the finalized codebook. Once finalized, the code book was used with qualitative analysis computer software for identification of major themes by two members on the research team with all meeting notes.