Adolescent and young adult cancers: unmet needs and closing the gaps.

PURPOSE OF REVIEW: There is a growing population of adolescent and young adult (AYA, ages 15-39 years) cancer patients and survivors, and the field of AYA oncology is rapidly evolving. Despite an increased focus on survival and quality of life for AYAs, gaps in knowledge remain. The current review focuses on what is known across several domains unique to AYA cancer care as well as areas of improvement and future directions in research and intervention. RECENT FINDINGS: Due to the developmental stages included in the AYA age range, a cancer diagnosis and treatment can affect relationships, education and employment, finances, and long-term health differently than diagnoses in younger or older populations. Recent studies that have focused on these unique aspects of AYA cancer care, including health-related quality of life (HRQoL), fertility, financial toxicity, barriers to clinical trial enrollment, genetic predisposition, and survivorship care are included in the current review. SUMMARY: Although studies have described many of the challenges faced by AYAs across the cancer continuum from diagnosis to survivorship, more work is needed, particularly in systematically measuring HRQoL, eliminating barriers to clinical trial enrollment, addressing financial toxicity, and increasing access to fertility preservation and high-quality survivorship care.

Children's Oncology Group 2023 blueprint for research: Adolescent and young adult oncology.

Over the past few decades, 5-year cancer survival has steadily improved for all adolescents and young adults (AYA, 15-39 years at diagnosis) combined. While encouraging, this progress simultaneously highlights a compelling need for improving survival in higher risk AYA subsets and for addressing health outcomes and health-related quality of life (HRQoL) among long-term survivors. The Children's Oncology Group (COG), in collaboration with the National Cancer Institute (NCI) and the adult network groups within the NCI National Clinical Trials Network (NCTN), has developed a large and growing portfolio of therapeutic AYA cancer clinical trials to identify optimal treatment approaches for common AYA cancers. Additional initiatives, led by the COG AYA Oncology Discipline Committee for increasing collaboration between the COG and the adult network groups, optimizing AYA clinical trial enrollment, and standardizing the assessment of HRQoL, have been highly successful to date. Further, NCTN-wide collaborations are currently underway focused on improving survival for AYA malignancies with poor prognosis and, through development of supportive care and care delivery trials, reducing the short- and long-term toxicity caused by cancer treatment. Leveraging the research infrastructure within the NCTN and the NCI Community Oncology Research Program, the COG will continue to champion meaningful advancements in health and survival for AYAs with cancer.

Genome-wide characterization of lncRNAs in acute myeloid leukemia.

Long noncoding RNAs (lncRNAs) are a large family of noncoding RNAs that play a critical role in various normal bioprocesses as well as tumorigenesis. However, the expression patterns and biological functions of lncRNAs in acute leukemia have not been well studied. Here, we performed transcriptome-wide lncRNA expression profiling of acute myeloid leukemia (AML) patient samples, along with non-leukemia control hematopoietic samples. We found that lncRNAs were differentially expressed in AML samples relative to control samples. Notably, we identified that lncRNAs upregulated in AML (relative to the control samples) are associated with a lower degree of DNA methylation and a higher ratio of being bound by transcription factors such as SP1, STAT4, ATF-2 and ELK-1 compared with those downregulated in AML. Moreover, an enrichment of H3K4me3 and a depletion of H3K27me3 were observed in upregulated lncRNAs in AML. Expression patterns of three types of lncRNAs (antisense, enhancer and intergenic lncRNAs) have previously been characterized. Of the identified lncRNAs, we found that high expression level lncRNA LOC285758 is associated with the poor prognosis in AML patients. Furthermore, we found that LOC285758 regulates proliferation of AML cell lines by enhancing the expression of HDAC2, a key factor in carcinogenesis. Collectively, our study depicts a landscape of important lncRNAs in AML and provides novel potential therapeutic targets and prognostic markers for AML treatment.

A critical role of epigenetic inactivation of miR-9 in EVI1high pediatric AML.

Ectopic Viral Integration site 1 (EVI1) upregulation is implicated in 10-25% of pediatric acute myeloid leukemia (AML) and has an inferior outcome with current chemotherapy regimens. Here we report that EVI1 upregulation is associated with methylation of the miR-9 promoter and correlated with downregulation of miR-9 in human AML cell lines and bone marrow (BM) cells from pediatric patients. Reactivation of miR-9 by hypomethylating agents and forced expression of miR-9 in EVI1high leukemia cell lines and primary leukemia cells results in apoptosis and decreased proliferation of EVI1high leukemia cells. Furthermore, re-expression of miR-9 delays disease progression in EVI1high leukemia-xenograft mice. Our results suggest that EVI1-induced hypermethylation and downregulation of the miR-9 plays an important role in leukemogenesis in EVI-1high pediatric AML, indicating that hypomethylating agents may be a potential therapeutic strategy for EVI1high pediatric AML.

Steroid Responsive Atypical Hemolytic Uremic Syndrome Triggered by Influenza B Infection.

Atypical hemolytic uremic syndrome (aHUS) is characterized by uncontrolled complement activation leading to thrombotic microangiopathy and severe end-organ damage. The most common trigger for an episode of aHUS in the background of genetic deregulation of the alternative complement pathway is systemic infection. There are only 4 reported cases of aHUS triggered by influenza B thus far. Current accepted therapies for aHUS include plasma exchange and eculizumab. We describe a unique patient with aHUS with a rare membrane cofactor protein mutation triggered by influenza B infection, who achieved complete remission with treatment with high-dose corticosteroids after failure of plasmapheresis.

Primary Orbital Histiocytic Sarcoma in a Child Successfully Treated With Multiagent Chemotherapy.

Histiocytic sarcoma (HS), a malignant proliferation of mature tissue histiocytes presenting with single or multifocal extranodal tumors, is rarely seen in children. Primary orbital HS has never been reported in a child. Disseminated disease to the bone marrow typically has an aggressive course and poor prognosis. There is no consensus currently on the optimal therapeutic approach for HS. We present the case of a 2-year-old girl with orbital HS with likely bone marrow involvement treated successfully with multiagent chemotherapy, now in complete remission and disease free 3.5 years from end of therapy.

A unique description of stage IV extranodal marginal zone lymphoma (EMZL) in an adolescent associated with gamma heavy chain disease.

Extranodal Marginal zone lymphoma (EMZL) is a rare, usually localized disease in children. Advanced stage EMZL in adults is considered incurable, with prolonged remissions after chemotherapy. Gamma heavy chain disease (γHCD) is a rare disease of adults associated with lympho-proliferative processes with no comparable reports in children. A case of stage-IV EMZL with γHCD in an adolescent is discussed including treatment with Bendamustine plus Rituximab. The patient remains disease free 18 months from diagnosis. This case highlights necessity for careful diagnostic work-up to identify indolent lymphomas in children which may respond to less toxic chemotherapy than used for common pediatric lymphomas.

Utilization of Teleconsent for Adolescent and Young Adult Cancer Clinical Trials, a Report from the Children's Oncology Group.

Purpose: Adolescents and young adults (AYAs, ages 15-39 years) are underrepresented in oncology clinical trials. Reasons for this include accessibility of the trial and whether the trial is presented to AYAs. The coronavirus disease 2019 (COVID-19) pandemic not only amplified these enrollment challenges but also presented opportunities for improving the enrollment process through virtual methods such as electronic informed consent and teleconsent. While AYAs are well positioned to take advantage of these opportunities, the extent to which institutions utilize remote enrollment processes is unclear. The goal of this study was to identify the utilization of and barriers to using teleconsent for AYA oncology clinical trials. Methods: The Children's Oncology Group (COG) AYA Responsible Investigator (RI) Network Teleconsent Working Group sought to understand teleconsent utilization both before and during the pandemic. The working group developed an online survey distributed via email to COG AYA RI Network members (n = 197). Results: The survey received 49 responses (25%) from 40 different institutions. Before the pandemic, 13% of respondents reported that their institution allowed study enrollment via teleconsent. After the pandemic, 23% reported using teleconsent for clinical trial enrollment and 38% reported changes in institutional Review Board policies and procedures allowing teleconsent. Respondents reported that the greatest benefit of teleconsent was patient convenience and the greatest barrier was institutional restrictions on teleconsent utilization. Respondents reported that sharing institutional guidelines would be the most helpful intervention to improve teleconsent adoption. Conclusion: Teleconsent is a promising but underutilized approach. Institutions should work together to address common challenges to accessibility and acceptance of clinical trials by AYA cancer patients.

Creation of a quality improvement collaborative to address adolescent and young adult cancer clinical trial enrollment: ATAQI (AYA trial access quality initiative).

Adolescent and young adult (AYA) participation in cancer clinical trials (CCTs) is suboptimal, hindering further improvements in survival, quality of life, and basic understanding of cancer pathophysiology in this population. Prior studies have identified barriers and facilitators to AYA CCT enrollment; however, few interventional studies have attempted to address these barriers and measure tangible changes. In September 2020, a task force was established to address CCT enrollment barriers at a multi-institutional level utilizing a quality improvement collaborative model for improvement. The AYA Trial Access Quality Initiative was developed with the goal of bring multidisciplinary teams together across multiple sites to learn, apply and share their methods of improvement. It uses a structured process of learning sessions lead by quality improvement and clinical experts who help facilitate learning and problem solving which are followed by action phases. During the pilot phase of the collaboration, one key driver of CCT enrollment in AYA's will be addressed: communication between adult and pediatric oncology by implementation of various interventions at sites. The number of AYAs screened for and enrolled on CCTs will be tracked over the course of the collaborative along with the process measures. It is expected that the interventions will promote engagement of stakeholders in the process of screening AYA oncology patients for eligibility on CCTs. This will hopefully create a favorable environment conducive for increasing enrollment on CCTs and lead to the development of a system-wide quality improvement framework to improve AYA CCT enrollment.

Shared barriers and facilitators to enrollment of adolescents and young adults on cancer clinical trials.

Adolescent and young adult (AYA) enrollment in cancer clinical trials (CCT) is suboptimal. Few studies have explored site level barriers and facilitators to AYA enrollment on CCTs and the efficacy of interventions to enhance enrollment. A cross sectional survey was developed by the COG AYA Oncology Discipline Committee Responsible Investigator (RI) Network to identify perceived barriers and facilitators to enrollment, as well as opportunities to improve enrollment. Associations of barriers and facilitators to enrollment with program demographics were assessed. The survey was sent to all AYA RI Network members (n = 143) and quantitative and thematic analyses were conducted. The overall response rate was 42% (n = 60/143). Participants represented diverse institutions based on size, presence or absence of dedicated AYA programs, and proximity and relationship between pediatric and medical oncology practices within the institution. The most frequently cited barriers to enrolling AYAs in CCTs were administrative logistical issues (45%), disparate enrollment practices (42%) and communication issues (27%) between pediatric and medical oncology and perceived limited trial availability (27%). The most frequently reported facilitators to enrollment included having strong communication between pediatric and medical oncology (48%), having a supportive research infrastructure (35%) and the presence of AYA champions (33%). Many barriers and facilitators were similar across institutions and AYA program types. Shared barriers and facilitators to AYA CCT enrollment exist across the landscape of cancer care settings. Interventions aimed at increasing coordination between pediatric and medical oncology clinical trials offices and providers have high potential to improve site-level AYA enrollment.

Maternal and Perinatal Outcomes of COVID-19-Positive Pregnant Women.

Background The risks of adverse maternal and perinatal outcomes are not very clear in coronavirus disease 2019 (COVID-19)-positive pregnant women. Therefore, this study aimed to determine the maternal and fetal outcomes in COVID-19-positive pregnancies. Methodology This prospective, cohort study was conducted in a tertiary care center over the period of one year. The study group comprised pregnant patients who presented with COVID-19 in the first and second waves of the pandemic. Maternal symptoms due to COVID-19 infection, comorbidities, number of admissions to the intensive care unit (ICU), and maternal mortality were noted for every patient. Perinatal outcomes were recorded in the form of intrauterine growth retardation (IUGR), mode of delivery, preterm deliveries, birth weight of newborns, neonatal intensive care unit (NICU) admissions, and neonatal mortality. Data analysis was done in the form of a variable percentage and mean ± standard deviation (SD). Results COVID-19-positive pregnant patients were mostly asymptomatic (48.07%). Term deliveries (37-40 weeks) were seen in 44 (89.8%) patients. The percentage of normal vaginal delivery was 74% and cesarean section was 24%. Out of 52 patients, two (3.8%) patients were admitted to the high dependency unit (HDU), one (1.9%) patient was admitted to the ICU, and 49 (94.3%) patients were in the isolation ward. Of the 49 live births, four (8.16%) newborns were admitted to the NICU. No neonatal death was recorded. Conclusions In this study, COVID-19-pregnant women were mostly asymptomatic. Neonates of COVID-19-infected women also mostly tested COVID-19 negative. More studies are needed with larger sample sizes to determine the effect of COVID-19 infection in pregnant women and neonates.

A Comparative Analysis of Nondescent Vaginal Hysterectomy, Laparoscopy-Assisted Vaginal Hysterectomy, and Total Laparoscopic Hysterectomy for Benign Uterine Diseases at a Rural Tertiary Care Center.

Objectives: The aim of this study was to compare operative data and postoperative complications among nondescent vaginal hysterectomy (NDVH), laparoscopy-assisted vaginal hysterectomy (LAVH), and total laparoscopic hysterectomy (TLH) at a rural tertiary care center. Materials and Methods: This is a prospective analytical study, of 145 hysterectomies for benign conditions with or without salpingo-oophorectomy in women from 30 to 60 years, over 3 years from January 2016 to December 2019, with 60 cases of NDVH, 46 cases of LAVH, and 39 cases of TLH. The three groups were compared intraoperatively in terms of blood loss, operating time, and intraoperative complications and postoperative complications and postoperative duration of hospital stay. Results: There was no significant difference between the three groups in terms of age, parity, body mass index, and indications for hysterectomies. The mean operative time was significantly shorter (P = 0.000) in the NDVH group (54.67 ± 15.67 min) as compared to the LAVH (102.45 ± 10.53 min) and TLH (126.79 ± 8.7 min) groups. Intraoperative blood loss was greater (P = 0.000) in the TLH group (111.025 mL ± 20.8) as compared to the NDVH (59.50 mL ± 16.7) and LAVH (91.85 mL ± 10.66) groups. The intraoperative complications and postoperative complications were higher in the TLH group as compared to the LAVH and NDVH groups. The duration of hospital stay was almost similar in all the groups. Conclusion: NDVH may be the preferred approach for experienced surgeons, as it is less time-consuming, has a small amount of blood loss, and is a scarless surgery, whereas LAVH and TLH may be the preferred approaches in the cases of presence of adnexal masses and adhesions or whenever salpingo-oophorectomy is indicated.

Comparative Analytical Study of Dinoprostone Gel and Hyaluronidase Injection for Induction of Labour in Term Primigravida in Tertiary Rural Medical Centre of Western Uttar Pradesh.

Objective: To compare the efficacy of intracervical dinoprostone gel and hyaluronidase injection for induction of labour in term primigravida. Materials and methods: This is a hospital based analytical prospective interventional study conducted in a rural tertiary care centre over a period of 18 months. A total of 70 patients who required induction of labour for one or another reason with Bishop score of less than 6 were included in the study. All the cases were randomly divided into two groups, Group A received dinoprostone gel and Group B received hyaluronidase injection. Chi square test & unpaired T test were applied for statistical analysis. Results: Time interval from induction to active phase of labour was comparatively shorter in group A than in group B (10.74 ± 6.17 vs 15.94 ± 7.1) and the difference was significant (p= 0.001). Time interval from induction to delivery time was comparatively shorter in group A than group B (14.84 ± 8.86 vs 21.33 ± 7.86) and difference was significant (P= 0.009). Maternal complications were more common in group A as compared to group B. Conclusion: This study showed that labour could be accelerated significantly by intracervical injection of hyaluronidase. Hyaluronidase injection has less maternal and fetal side-effects as compared to dinoprostone gel and can be a good choice for induction of labour.

Barriers to Pediatric Oncologist Enrollment of Adolescents and Young Adults on a Cross-Network National Clinical Trials Network Supportive Care Cancer Clinical Trial.

Few studies have explored interventions to improve adolescent and young adult (AYA) cancer care delivery. While many AYAs receive cancer care at NCI Community Oncology Research Program (NCORP) sites, few enroll on clinical trials. Barriers and facilitators to pediatric oncologist activation of and enrollment on an AYA cross-network National Clinical Trials Network (NCTN) supportive care trial were assessed using a survey that was administered to 162 stakeholders representing all 47 children's oncology group (COG) institutions affiliated to an NCORP. Fifty-eight stakeholders participated representing 62% of all sites surveyed. Approximately half of participants (45%) were unaware of the trial. Seven sites had the study open and one enrolled a patient. Reasons for not opening and enrolling on the trial included limited research staff and resources, low anticipated accrual, and lower prioritization of the trial. Enrollment facilitators included having a local "AYA champion," improving communication between pediatric and medical oncology, and having site education on available AYA trials. Interventions focused on increasing site and provider awareness of AYA trials and decreasing local barriers to AYA enrollment are needed.

Use of Communication Technology to Improve Clinical Trial Participation in Adolescents and Young Adults With Cancer: Consensus Statement From the Children's Oncology Group Adolescent and Young Adult Responsible Investigator Network.

Adolescents and young adults (AYAs; age 15-39 years) with cancer are under-represented in cancer clinical trials because of patient, provider, and institutional barriers. Health care technology is increasingly available to and highly used among AYAs and has the potential to improve cancer care delivery. The COVID-19 pandemic forced institutions to rapidly adopt novel approaches for enrollment and monitoring of patients on cancer clinical trials, many of which have the potential for improving AYA trial participation overall. This consensus statement from the Children's Oncology Group AYA Oncology Discipline Committee reviews opportunities to use technology to optimize AYA trial enrollment and study conduct, as well as considerations for widespread implementation of these practices. The use of remote patient eligibility screening, electronic informed consent, virtual tumor boards, remote study visits, and remote patient monitoring are recommended to increase AYA access to trials and decrease the burden of participation. Widespread adoption of these strategies will require new policies focusing on reimbursement for telehealth, license portability, facile communication between electronic health record systems and advanced safeguards to maintain patient privacy and security. Studies are needed to determine optimal approaches to further incorporate technology at every stage of the clinical trial process, from enrollment through study completion.

Experience on Safety, Expulsion, and Complication of Intracesarean Post-Partum Intrauterine Copper Device.

Background The post-partum period is one of the critical times when ovulation is highly unpredictable and couples often underestimate the likelihood of pregnancy. According to the World Health Organization, intrauterine copper device (IUCD) can be inserted within 48 hours post-partum, referred to as post-partum IUCD (PPIUCD). The objectives of the present study were to determine the safety and expulsion of intracesarean PPIUCD. This study also has an objective to determine the complications (undescended/missed thread, bleeding, pain, and infection) following intracesarean PPIUCD insertion among the women. Materials and methods This was a prospective interventional hospital-based study conducted in the Department of Obstetrics & Gynecology, Uttar Pradesh University of Medical Sciences, Saifai, Etawah, Uttar Pradesh, India, from November 1, 2016, to October 31, 2019. Women were followed up at six weeks and six months for various objectives. Results Intracesarean PPIUCD was inserted in a total of 1,586 patients, and 1,029 cases came for follow-up at six weeks and six months; thus, the concluded sample size was 1,029. The majority of patients were of 20 to 25 years of age, belonged to rural areas, and were having parity 2. The most common complaint was of undescended/missed thread in 22.2% women followed by bleeding (11.9%), expulsion (2.2%), pain (2%), and local infection (1.3%) at six weeks follow-up. At six months, the most common complaint was missed thread in 8.6% followed by bleeding (6.0%), pain (1.6%), expulsion (1.2%), and local infection (0.7%). There was no case of perforation. While 19.05% women wanted the removal of PPIUCD, but at the end of the study period, it was removed in a total of 11.27% cases due to various reasons. Conclusions PPIUCD is an effective tool to reduce the unmet need of contraception. This study showed that most of the women were satisfied with the intracesarean insertion of IUCD, indicating its important place within the basket of post-partum family planning methods.

The Children's Oncology Group Adolescent and Young Adult Responsible Investigator Network: A New Model for Addressing Site-Level Factors Impacting Clinical Trial Enrollment.

Purpose: In the Children's Oncology Group (COG), there is precedent for scientific committees designating institutional Responsible Investigators (RIs) to promote clinical trial enrollment and coordinate related research activities. In response to low enrollment of adolescents and young adults (AYAs) on COG clinical trials, the COG AYA RI Network was established. Leveraging this network, we undertook an initiative to identify site-level factors influencing AYA enrollment. Methods: The overarching goal of the AYA RI Network is to increase AYA enrollment onto COG trials. At each site, RIs highlight AYA disparities, facilitate activation of relevant trials, improve recruitment processes, and expand interactions with medical oncologists. Through a series of monthly national webinars and workshops, participating RIs reported local barriers and facilitators enrolling AYAs. A mixed-methods approach was utilized to determine major themes of factors affecting site-level enrollment. Results: For this report, there were 145 participating RIs representing 122 demographically and geographically diverse sites. There were 13 interactive webinars and 3 symposia involving 25 speakers focused on addressing enrollment barriers. Major thematic categories for site-level barriers were (1) Lack of available trials; (2) Poor communication between pediatric and medical oncology; (3) Logistical constraints to accessing trials; and (4) Need for leadership support, sufficient resources and appropriate policies. Conclusion: The COG AYA RI Network has identified multiple site-level barriers impeding AYA clinical trial enrollment and represents a novel model for developing and implementing appropriate solutions through a nationally coordinated strategy.