Young Cancer Patients Research Articles

P–459 Ex vivo perfusion of whole ewe ovaries with follicular maturation for up to seven days: towards the development of an alternative fertility preservation method

Abstract Study question To develop an alternative fertility preservation method for young female cancer patients based on an ex vivo perfusion of whole ovaries serving as a platform for future ovarian stimulation studies. Summary answer It is possible to maintain viable follicles and to retrieve oocytes after ex vivo perfusion of ewe ovaries for up to 7 days. What is known already Some progress has been made in terms of follicular growth and the isolation of mature oocytes in vitro. However, full development, from early follicular stages to a viable offspring, has only been described in rodent models. The complex events controlling follicular expansion and the long time required for folliculogenesis and oocyte maturity in large mammalian species creating challenges and limitations for in vitro studies. Ex vivo perfusion of a whole ovary could potentially be a solution by exploiting the intact ovarian architecture to support folliculogenesis and oocyte maturation. Study design, size, duration Thirty-one ewe ovaries were divided into 4 groups and ex vivo perfused in a bioreactor. Group 1 (n = 14) perfusion for 48 hours with no hormone supplementation; Group 2 (n = 4) perfusion 96–101 hours with follicle stimulating hormone (FSH); Group 3 (n = 3) perfusion 120–168 hours with human menopausal gonadotropin (hMG); Group 4 (n = 10) perfusion 72–144 hours with hMG. Participants/materials, setting, methods Ewe ovaries from sexually mature ewes were ex vivo perfused in a bioreactor under normothermic conditions for up to 7 days (max total 168 hours). Histomorphological, immunohistochemical, hormonal and biochemical analyses were performed to assess ovarian structure and viability after cold ischemia and after perfusion which was subsequently compared to control ovaries. Main results and the role of chance The perfused ovaries in group 2 and 3 showed no significant differences in follicular density, viability and oocyte quality after ischemia and perfusion compared to control ovaries. Estradiol and progesterone levels did not increase during the perfusion. The perfused ovaries in group 1 and 4 showed a significant decrease in the ovarian reserve and oocyte quality. In total, 16 GV-MI oocytes were retrieved from groups 3 and 4. Limitations, reasons for caution 1. Ovaries were retrieved from ewes of unknown cycle and reproductive history. 2. The perfusion medium was changed after 24 hours from perfusion start to remove detrimental metabolites and this could affect the measured concentrations of hormones and metabolites in the perfusion medium. Wider implications of the findings: These results pave the way to propose ex vivo perfusion as a good platform for fertility preservation studies on whole mammalian and human ovaries to retrieve fully mature oocytes. Trial registration number Not applicable

P–699 Multi-scale study of the architecture, topography and mechanics of the human ovary from prepuberty to menopause: a blueprint for next-generation bioengineering and diagnosis

Abstract Study question Does the ovarian ECM have a precise and unique biophysical phenotype, specific to each age, from prepuberty to menopause? Summary answer Differences between healthy prepubertal, reproductive-age, and menopausal ovarian tissue, unravel and elucidate a unique biophysical phenotype of reproductive-age tissue, bridging biophysics and female fertility. What is known already Ovarian engineering has recently emerged to respond to patient needs and offer reliable models for basic research. It has relied on synthetic and natural biomaterials and microfluidics. However, these techniques were designed based on knowledge acquired from 2D cell culture and animal models. Our lack of information on the human ovary hampers our ability to mimic the main features of this organ, for clinical applications. The complex composition and hierarchical structure of its ECM complicates the design of truly biomimetic constructs, notably: fiber morphology, interstitial and perifollicular fiber orientation, porosity, topography, and viscoelasticity, which all play a role in mechanotransduction. Study design, size, duration Ovarian biopsies were taken from prepubertal (mean age [±SD]=7±3 years, n = 21), reproductive age (mean age [±SD]=27±5, n = 26 ) and menopausal (mean age [±SD]=61±6 years, n = 29) patients after obtaining their informed consent. All participating adult subjects were undergoing laparoscopic surgery for benign gynecological diseases not affecting the ovaries. Prepubertal tissue was derived from young cancer patients scheduled for ovarian cortex cryopreservation as a fertility preservation strategy, before being subjected to acute gonadotoxic cancer treatments. Participants/materials, setting, methods All samples were cryopreserved by slow freezing and kept frozen until the day of their analysis. Tissues provided from the same patients (n = 5 per age group) were investigated by scanning electron microscopy (SEM) (fiber, pore and topography analyses) and atomic force microscopy (AFM). A larger number of paraffin-fixed biopsies (prepubertal, n = 16, reproductive-age, n = 21, and menopausal, n = 24) obtained from the biobank of St-Luc’s Hospital were used to conduct computed fiber orientation analysis. Main results and the role of chance Our results revealed a unique ECM architecture at reproductive age, where fibers of intermediate diameter are assembled into thickest bundles compared to prepubertal and menopausal tissues(p < 0.0001). Indeed, during prepuberty the bundles assemble into a tight network with high number of small pores while reproductive-age ovary gain more porosity(p < 0.0001). However, at menopause tissue pore number and area change significantly(p < 0.001). These pore geometry and distribution changes contribute to diffusion and access of key molecules to/from cells, which can be translated into changes in permeability and molecule selectivity with age. Fiber directionality around follicle borders at preantral stages revealed that before and after puberty, secondary follicles appear to modify their microenvironment arrangement locally compared to follicles at earlier stages of development (p < 0.01), by reorienting the majority of collagen fibers below 50°.This could indicate that follicles at this stage require higher fiber contact and adhesion signaling to complete their development and maturation towards ovulation. AFM evidenced a relatively rigid ovarian tissue at prepuberty, softening significantly at reproductive age, then stiffening considerably upon menopause. These differences(p < 0.01) are not only structure-dependent, but also related to biochemical differences in ECM composition, as previously demonstrated in our follow-up of variations in elastic matrisome components from prepuberty to menopause. Limitations, reasons for caution The samples represent single time points from each age group which could present limitations, since following ovary dynamics from prepuberty to menopause in the same patient is not feasible. Wider implications of the findings: Our study provides the first conclusive proof of a link between ECM biophysics and fertility by comparing different stages of ovarian transformation related to a woman’s reproductive life, which will oriente new strategies for infertility prognoses based on ECM biophysics and may become a blueprint for designing functional engineered ovaries. Trial registration number Not applicable

P–442 Cancer does not adversely affect oocyte maturation in vitro with the exception of breast cancer

Abstract Study question Do different types of cancer affect the success of oocyte maturation in vitro compared to infertile women included in the in vitro fertilization (IVF) program? Summary answer Cancer does not adversely affect oocyte maturation in vitro, with the exception of breast cancer, compared to infertile women in the in vitro fertilization program. What is known already Vitrification and storage of oocytes in liquid nitrogen is one of the real options for maintaining reproductive function in cancer patients. Despite careful hormonal stimulation of the ovaries, however, the proportion of oocytes is immature and lost to the patient. In vitro maturation of oocytes can play an important role in resolving immature oocytes and increasing the chances of conception in cancer patients. Moreover, it can mean a safe way to store oocytes when ovarian hormonal stimulation could worsen the disease. Therefore, the aim of this study was to determine whether different types of cancer affect oocyte in vitro maturation. Study design, size, duration After ovarian stimulation in 18 cancer patients, the number and maturity of oocytes were compared to 21 infertile patients in the IVF program over a three-year period. In both groups, 119 germinal vesicle-GV oocytes were matured in vitro to compare the maturation rate. After IVF in a subset of 17 infertile patients, the fertilization of in vitro and in vivo matured oocytes was compared in the same cycles. The procedure was considered in cancer patients. Participants/materials, setting, methods In this prospective study, forty-five GV oocytes in cancer patients and 74 GV oocytes in infertile patients underwent in vitro maturation procedure. Each oocyte was matured in vitro in the MediCult IVM System by conditioning in LAG medium and maturation for up to 28 hours in IVM medium with added hormones FSH and hCG, in coculture with cumulus cells from mature oocytes in the same patients. Oocytes were fertilized by intracytoplasmic sperm injection (ICSI). Main results and the role of chance After controlled ovarian hormonal stimulation, 198 oocytes were retrieved in cancer patients and 259 oocytes in infertile women and there were no significant differences in the number of retrieved oocytes, proportion of degenerated oocytes and proportion of GV oocytes. In cancer patients, the proportion of oocytes that matured in vitro was lower than in infertile patients (66.0 vs. 80.0%), but the difference was not significant. Among cancer patients, the oocyte maturation rate tended to be lower in patients with breast cancer than in patients with other cancers (54.5% vs. 81.2%; difference not significant). However, in patients with breast cancer, significantly fewer oocytes matured in vitro than in infertile patients (54.5% vs. 80.0%; P < 0.05, Chi-Square test) even though they tended to be younger (29.3 ± 7.4 vs. 33.4 ± 5.0 years; non-significant difference). After in vitro maturation, there was a 13% increase in mature oocyte yield in cancer patients and a 20.1% increase in infertile women with no significant difference observed. After ICSI in a subset of infertile women, there was approximately the same fertilization rate between oocytes matured in vitro and in vivo (55.1% vs. 57.0%) in the same cycles. Limitations, reasons for caution For ICSI in oocytes matured in vitro, we had to use semen collected the day before, while oocytes matured in vivo were fertilized with fresh semen in the same cycle. Therefore, we could not compare the development of embryos in both groups. Wider implications of the findings: In vitro maturation of oocytes in connection with their vitrification or vitrification of embryos after their fertilization appears to be a valuable way to maintain the fertility of young cancer patients, but a worse outcome is expected in breast cancer patients. Trial registration number National Medical Ethical Committee Approval, No. 0120–222/2016–2; KME 115/04/16.

A simple test-based frailty index to predict survival among cancer patients with an unplanned hospitalization: An observational cohort study.

BackgroundFrailty is a state of increased vulnerability to stressors, and predicts risk of adverse outcomes, such as mortality. Frailty can be defined by a frailty index (FI) using an accumulation of deficits approach. An FI comprised of 20 items derived from our previously studied test‐based frailty index (TBFI) and an additional 33 survey‐based elements sourced from the standard CGA was developed to evaluate if predictive validity of survival was improved.MethodsOne hundred eighty‐nine cancer patients during acute hospitalization were consented between September 2018 and May 2019. Frailty scores were calculated, and patients were categorized into four groups: non‐frail (0–0.2), mildly frail (0.2–0.3), moderately frail (0.3–0.4), and severely frail (>0.4). Patients were followed for 1‐year to assess FI and TBFI prediction of survival. Area under the curve (AUC) statistics from ROC analyses were compared for the FI versus TBFI.ResultsIncreasing frailty was similarly associated with increased risk of mortality (HR, 4.5 [95% CI, 2.519–8.075] and HR, 4.1 [95%CI, 1.692–9.942]) and the likelihood of death at 6 months was about 11‐fold (odds ratio, 10.9 [95% CI, 3.97–33.24]) and 9.73‐fold (95% CI, 2.85–38.50) higher for severely frail patients compared to non‐frail patients for FI and TBFI, respectively. This association was independent of age and type of cancer. The FI and TBFI were predictive of survival for older and younger cancer patients with no significant differences between models in discriminating survival (FI AUC, 0.747 [95% CI, 0.6772–0.8157] and TBFI AUC, 0.724 [95% CI, 0.6513–0.7957]).ConclusionsThe TBFI was predictive of survival, and the addition of an in‐person assessment (FI) did not greatly improve predictive validity. Increasing frailty, as measured by a TBFI, resulted in a meaningfully increased risk of mortality and may be well‐suited for screening of hospitalized cancer patients.

Menopausal symptoms, sexual dysfunction, and hormone therapy use in young cervical cancer patients undergoing definitive treatment at a single institution

<h3>Objectives:</h3> To evaluate the incidence of menopausal symptoms, sexual dysfunction, and hormone therapy (HT) use in cervical cancer patients at a single public hospital. <h3>Methods:</h3> This is a retrospective cohort study evaluating all patients under the age of 55 with stage IA1-IVA squamous cell carcinoma (SCC) or adenocarcinoma of the cervix who underwent definitive treatment at our institution between 2015 and 2018. Demographic data, tumor characteristics, and treatment data were collected. All gynecologic and radiation oncology visits were reviewed for documentation of menopausal symptoms, sexual dysfunction, and use of HT and vaginal dilators. The frequency of these symptoms was measured as was the time a provider first documented them and readdressed them after diagnosis and initiation of treatment. <h3>Results:</h3> A total of 59 patients were identified, with a mean age of 42 years (range 27-55, 76% ≤50 years) and 83% Hispanic. 32% had clinically early stage disease (IB1 or less) and 68% had locally advanced disease. 68% had SCC, 24% adenocarcinoma and 8% adenosquamous carcinoma. Median recurrence free survival was 20 months (range 1-53) with median follow-up of 25 months (range 4-58). Ten women (17%) underwent hysterectomy or trachelectomy with ovarian conservation, and 1 (2%) underwent bilateral salpingo-oophorectomy (BSO) at the time of radical hysterectomy. 39 women (66%) underwent definitive chemoradiation. The remaining 9 (15%) women underwent surgery (hysterectomy and/or BSO) and adjuvant radiation. A total of 827 visits (median 14 per patient) were reviewed after diagnosis. Of the 48 women who received any radiation, only 27 (56%) were ever asked about vasomotor symptoms with a median time to asking of 19 weeks (range 1-132). When first asked, vasomotor symptoms were reported 71% of the time, but symptoms were only readdressed in 20% of subsequent visits. When first asked, 55% of patients reported vaginal dryness and 60% had sexual dysfunction. 24 patients (50%) were prescribed any kind of HT, and median time to counseling on HT use was 16 weeks (range 1-184). Once initiated, ongoing HT use was readdressed at 74% of visits. Of the 35 patients (73%) ever asked about vaginal dilator use, 54% reported use. None of the 11 patients who underwent hysterectomy±BSO without radiation were asked about the domains studied in any of their 70 visits. <h3>Conclusions:</h3> When asked, the majority of young cervical cancer patients report menopausal symptoms and sexual dysfunction after undergoing definitive treatment. Once initiated, women are compliant with HT use. However, many women are not being counseled about menopausal or sexual dysfunction symptoms nor treated with hormone therapy in a timely fashion. This study identified opportunities for quality improvement at our institution and will be combined with national guidelines to change clinical practice.

A Questionnaire Survey on Adolescent and Young Adult Hiroba, a Peer Support System for Adolescent and Young Adult Cancer Patients at a Designated Cancer Center in Japan.

Adolescent and young adult (AYA) cancer patients have few opportunities to interact with peers in the hospital. AYA Hiroba, a peer support system for AYA cancer patients, was launched and held regularly at the National Cancer Center Hospital in Japan. This questionnaire survey was conducted to investigate the degree of satisfaction and opinions of AYA cancer patients regarding this program. Participants reported that the content was satisfying and useful. Their impressions suggested that AYA Hiroba is potentially effective for promoting interaction with the same generation, change in mood, and acquisition of information.

Molecular Mechanism and Prevention Strategy of Chemotherapy- and Radiotherapy-Induced Ovarian Damage.

Fertility preservation is an emerging discipline, which is of substantial clinical value in the care of young patients with cancer. Chemotherapy and radiation may induce ovarian damage in prepubertal girls and young women. Although many studies have explored the mechanisms implicated in ovarian toxicity during cancer treatment, its molecular pathophysiology is not fully understood. Chemotherapy may accelerate follicular apoptosis and follicle reservoir utilization and damage the ovarian stroma via multiple molecular reactions. Oxidative stress and the radiosensitivity of oocytes are the main causes of gonadal damage after radiation treatment. Fertility preservation options can be differentiated by patient age, desire for conception, treatment regimen, socioeconomic status, and treatment duration. This review will help highlight the importance of multidisciplinary oncofertility strategies for providing high-quality care to young female cancer patients.

Initiation and changes in use of social media for peer support among young adult cancer patients and survivors.

Social isolation is a prominent challenge for many young adults with cancer. Despite desires for peer-to-peer connections through technology, little is known about how young adults initiate or use social media for support over time. We interviewed young adults with cancer (n=45; age 18-39, in or post cancer treatment) to explore their initiation of social media for support, changes in use over time, and types of connections sought. Young adults with cancer learn about online support through individual personal recommendations, advocacy organizations, or searching on Google or social media. Most were reluctant to use social media support initially because of feeling overwhelmed-from diagnoses, abundance of online information, or demands of participation-and joined when informational and emotional needs arose. Many wished they had joined earlier. Some participants use social media to make close connections while others simply want to "see" others' shared experiences or crowdsource information. Young adults with cancer often haphazardly find online support from personal recommendations or Internet searches. Desires for social media connections are not one-size-fits-all; there are important audience segmentations for the degree and type of peer support. Better promotion of online social support options and benefits-early in one's cancer timeline and systematically through healthcare providers, cancer organizations, or family and friends-could improve access to helpful peer-to-peer support.

Abstract 2629: Young onset colorectal cancer patients, survivors and caregivers: self-report clinical, psychosocial, financial and quality of life outcomes

Abstract Background: Colorectal cancer is the third-most commonly diagnosed cancer and the second-leading cause of cancer death in men and women combined in the United States. Young-onset colorectal cancer refers to individuals diagnosed under the age of 50. In recent years, the incidence has increased by 2.2% annually in individuals younger than 50 years, and 1% in individuals 50-64, in contrast to a 3.3% decrease in adults 65 years and older. Young-onset (YO) CRC patients and caregivers face unique clinical challenges including fear and stress around the disruption of family and career developmental tasks and goals suggesting a need for additional psychosocial and financial support. Methods: A cross-sectional study, conducted in the form of an online survey, was launched to better understand the experiences of YO-CRC patients and caregivers. YO-CRC patients and survivors (N=885) and caregivers (N=204) completed an online questionnaire that was based on established instruments including PROMIS, EORTC-QOL-30, and EORTC-CR-29. The final survey instrument and study plan were reviewed and approved by the Aspire Inc. Institutional Review Board. Results: Nearly 75% of patients/survivors shared that they have been concerned about their mental health and 64% responded that they have needed help for their depression. Further, 67% of caregivers surveyed responded that they were also concerned about their own mental health and 68% responded that they needed help with their depression. Emotional exhaustion was reported by 77% of caregivers, whether they were providing round-the-clock care or caregiving from a distance. Emotional exhaustion was more pronounced in the patient/survivor cohort, with 95% indicating that emotional exhaustion impacted their lives. As a result of psychosocial distress, 71% of caregivers and 29% of patients/survivors indicated that they had withdrawn from other people. YO-CRC diagnosis changes what the patient/survivor can contribute to the family, both physically and emotionally, resulting in the caregiver having a change in their previous responsibilities. Of our respondents, 48% of caregivers indicated that their role in childcare changed; in addition, changes occurred in household responsibilities (77%), sexual/intimacy (51%), work (59%), and financial responsibility (42%). Conclusions: These survey results indicate a need for the YO-CRC community to have access to resources to address unique issues. The physical and emotional stress on patients, survivors and caregivers is frequently not discussed which indicates a knowledge gap, not only in the lay population but also within the medical community. The Alliance is dedicated to working with all stakeholders, including policymakers, to address the unmet needs among caregivers, aiming to improve quality of life outcomes for caregivers in conjunction with their patients. Citation Format: Kimberly Lynn Newcomer, Ronit Yarden, Laura Porter. Young onset colorectal cancer patients, survivors and caregivers: self-report clinical, psychosocial, financial and quality of life outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2629.

Metastatic patterns and prognosis of young lung cancer patients: a population-based study by age.

BackgroundWe aimed to examine the different metastatic patterns and corresponding survival outcomes between all ages of young (aged <60 years) and elderly lung cancer patients.MethodsLung cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were divided into a young and elderly group. The young group was subdivided into four consecutive subgroups. Baseline characteristics were analyzed by the Chi-square test. Survival differences were evaluated by Kaplan-Meier curves and Cox proportional hazards models.ResultsOf the total 200,362 lung cancer patients, 155,348 were elderly patients and 45,014 were young patients, including 3,461 aged <45 years, 5,697 aged 45–49 years, 13,645 aged 50–54 years, and 22,211 aged 55–59 years. Compared with elderly lung cancer patients, extrathoracic metastases were significantly more frequent in each younger group, irrespective of the site and number of extrathoracic metastatic organs. Regardless of metastasis patterns, young ages were independent prognostic factors of lung cancer-specific survival (LCSS) [<45 years: hazard ratio (HR): 0.70; 45–49 years: HR: 0.87; 50–54 years: HR: 0.90; 55–59 years: HR: 0.93, all P values were <0.001]. In each age subgroup, patients with multi-organ extrathoracic metastasis had the worst LCSS.ConclusionsYoung lung cancer patients across all ages were at increased risk of extrathoracic metastasis, especially multi-organ patterns, but had a reduced risk of lung cancer-related death compared to elderly patients. Regular and meticulous monitoring of potential metastasized organs is required in young lung cancer patients throughout the follow-up period.

Abstract 810: Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort

Abstract Background: Li-Fraumeni syndrome (LFS) is a rare autosomal dominant inherited cancer syndrome; clinical diagnosis of it is mainly based on familial and personal history of cancer. Currently, most clinicians are lack of knowledge and experience of this rare disease, resulting in a difficulty to identify it. Consider that this is a rare tumor-type syndrome and 60-80% of the patients have germline variants of TP53, herein, we analyzed germline pathogenic/likely pathogenic (P/LP) TP53 variants in a Chinese tumor cohort with unknown familial history, and successfully established an analysis process to better screen for LFS patients. Methods: We retrospectively analyzed the germline TP53 mutations of a total of 19,226 Chinese tumor patients with unknown familial history. The screening process of LFS patients was as follows: 1) Germline P/LP TP53 variants must satisfy P/LP in any of the three databases: UMD_TP53, ClinVar or HGMD. It also must be defined as “non-functional” mutations in IARC database which includes all TP53 germline mutations of clinically determined LFS patients; 2) Follow up the familial and personal histories of patients with germline P/LP TP53 variants. Results: After screening, 26 germline P/LP TP53 variants were obtained, which involved 54 patients, mainly in brain cancer (34 pts) and lung cancer (9 pts). The median age of these 34 brain cancer patients was younger than that of 5,845 brain cancer patients in the cohort (28 vs. 44 year-old). Yet no such phenomenon was observed in lung cancer. It is necessary for young brain cancer patients to detect germline TP53 mutations. We then analyzed the relationship between germline P/LP TP53 variants and LFS in the 54 patients. According to the Chompret criterion of LFS, two patients who respectively had adrenocortical carcinoma (R175H of TP53) and choroid plexus carcinoma (G245S) were both LFS patients regardless of whether they had a familial history. We finally obtained follow-up information of 17 patients. Among them, four brain cancer patients (R248Q/R158H/C238Y/M237I), one lung cancer patient (R175H) and one leiomyosarcoma patient (R213Q) had family members who had cancers before 46-year-old. Another brain cancer patient (G245S; 1/17) had more than one cancer before 46-years-old. Hence, these seven patients (7/17; 41.18%) were also defined as LFS patients by the Chompret criterion. In total, 9 patients had LFS. It shows a high positive detection rate in our cohort by our analysis process. Conclusions: We have established an analysis process based on germline P/LP TP53 variants, which can efficiently screen for LFS patients in clinic. Citation Format: Changyu Lu, Yu Fang, Fachen Zhou, Yuntong Liu, Hongchuan Niu, Kai Li, Tonghui Ma, Xiaoyan Zhang. Enrichment and screening of LFS patients by analyzing TP53 germline mutations of a Chinese cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 810.

The young oral cancer patient: observations from the Hong Kong population

Oral squamous cell carcinoma (OSCC) is a lethal and deforming disease of rising global significance. Although traditionally presenting in older patients, evidence suggests that OSCC is increasingly...

Study on the clinical characteristics of young age pancreatic cancer using KOTUS registry

As the number of young patients diagnosed with pancreatic cancer increases, it is necessary to study the clinical characteristics of young pancreatic cancer patients. To date, there have been few studies of pancreatic cancer occurring at a young age. We evaluated clinical characteristics and survival rate of pancreatic cancer in young age using the KOTUS registry. A retrospective analysis of patients of pancreatic cancer from the KOTUS registry enrolled from 1991 to 2020. We compared demographics and clinical outcomes in patients who were younger than 45 (young age group) and older than 65 years (old age group). We estimated survival curve using the Kaplan-Meier method and hazard ratio by cox proportional hazard model. The total data was 5,617 patients, and 2,312 patients were analyzed, excluding patients with insufficient records. The old age group was 2,193 patients, and young age group was 193 patients. There were no statistically significant differences in overall survival and recurrence free survival between two groups in the total data. In the analysis of according to the stage, in Stage II-III, the rate of receiving adjuvant treatment was high in the young age group. As a result of analyzing only patients after 2016, by considering the period effect, the result of 5-year overall survival was statistically significant lower in the young age group (HR = 1.9, p = 0.04). Young age pancreatic cancer patients have the high rate of receiving adjuvant treatment, survival benefit can be obtained. Active treatment should be recommended for young patients.

Digital Phenotyping and Dynamic Monitoring of Adolescents Treated for Cancer to Guide Intervention: Embracing a New Era.

Adolescents diagnosed with and treated for cancer represent a particular vulnerable patient population with unique and complex medical and psychosocial needs that extend beyond the completion of treatment (1–4). These cancer patients are in the most critical phases of their development (5–7), with brain, body, mind, and social environment in constant transformation conferring vulnerability to some individuals and resilience to others. Adolescence is characterized by a heightened incidence (and first onset) of various mental illnesses (8–10). Cancer during adolescence influences peer relationships, changes mood and behavior, interferes with cognitive functioning, educational achievement, and increases the risk for the onset of psychopathology (11, 12). Furthermore, treatment is often accompanied by numerous physical and psychological symptoms such as nausea, vomiting, sleep disturbance, fatigue, pain, changes in body weight and body-image (2), treatment-induced psychosis, depression, and anxiety. Importantly, peer interactions in young cancer patients is often suddenly interrupted putting them at a higher risk for the development of emotional and behavioral problems. Even though many of these concerns remain largely unattended because of a lack of timely detection and management (13, 14), recent data indicate a growing awareness of the specific needs of this patient population suggesting that a concerted effort should be made to develop age-appropriate resources that could help them manage their illness and its treatment (15). When asked, adolescents indicate five domains of concern: 1) physical, emotional, behavioral, and mood problems related to treatment; 2) psychosocial issues; 3) present and future adjustments once the therapy has finished; 4) transition, organization, and management of survivorship; and 5) need to be better connected, involved, and informed (16–20). Given this, it is vital to capture, as early as possible, the biological, psychological, emotional, behavioral, and social modifications in young cancer patients to expand our day-to-day understanding of the factors affecting their vulnerability. Most importantly, reviews and guidelines based on best practice stress the fact that cancer in adolescents does not always have chronic negative outcome especially if we understand which individuals are at heightened risk (20). Any issue in the five domains of concern listed above must be detected early to put timely and preventive measures into place (21). Adolescent cancer patients represent an enormously heterogenous group and while most somatic treatments are accompanied by the development of acute or chronic unwanted effects (2, 4), we currently lack the capacity to distinguish individual trajectories leading to increased vulnerability or resilience. A paradigm shift is essential to detect the distinct clinical pathways of high-risk individuals (22–24). Current innovative digital approaches to patient care and monitoring offer a unique opportunity to create predictive models of individual vulnerability based on the integration and interdependencies of diverse sources of information. The analysis of the data contained in these platforms allow the projection of potential outcomes and disease trajectories, identifying those patients that are progressing from generic vulnerability to becoming at high risk for a negative event. Digital tools may have numerous potential benefits compared to traditional assessments: they are non-invasive, ecological, do not demand extra efforts, and provide continuous access which offers timely understandings of the emotional, behavioral, cognitive, and treatment related changes. Also, while not all studies underline a clear benefit, some of them indicate that they are unrestricted by time and place, and offer immediate access to data and intermediate endpoints, reduce stressful visits, remove barriers to access to care (fear, isolation), stimulate patient empowerment, and, most importantly, help in the identification of high-risk patients and their risk stratification (23–26). As a result, the integration of various digital tools in a “toolbox,” would offer a concrete opportunity to modify, replace, or accompany the current more categorical approach and shift to a multimodal dimensional methodology (27, 28) in which evidence is gathered from different domains, ranging from subtle neurocognitive disfunction (29–33) to biomarkers. Ultimately, the multidimensional continuous recording of data and especially their dynamic relationships would become an integral part of the care plan and serve as specifiers of an high-risk status (34, 35).

A Coordinated Clinical Center for Young Onset Colorectal Cancer.

The increase in young onset colorectal cancer and the complex care needs of young cancer patients spurred the development of the Center for Young Onset Colorectal Cancer at the Memorial Sloan Kettering Cancer Center. This article describes the lessons of the first 2 years at the Center, including development of the program and specific services provided.

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients.

BackgroundThe incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population.MethodsWe identified 6708 young adults aged 18–45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan–Meier estimation, log rank test, and multivariate Cox proportional hazards model.ResultsSixty‐three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31–0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43–0.49, p < 0.001 and HR 0.64, 95% CI: 0.55–0.76, p < 0.001, respectively).ConclusionThis is the largest observational study to evaluate survival outcomes in young‐onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.

Work ability and cognitive impairments in young adult cancer patients: associated factors and changes over time—results from the AYA-Leipzig study

PurposeAlthough young adults represent a significant portion of the working population, little is known about the work ability and cognitive impairments in adolescent and young adult (AYA) cancer patients (including the long-term course) following cancer treatment.MethodsAs part of the AYA-Leipzig study, we surveyed AYA cancer survivors (aged 18–39 years at diagnosis; time since diagnosis ≤ 4 years, including all cancer diagnoses) at two time points (t2 = 12 months after t1). Work ability (Work Ability Index, WAI-r) and cognitive impairments (Copenhagen Psychosocial Questionnaire, COPSOQ) were compared at both time points. We analysed predictors for work ability at, on average, 2 years post cancer diagnosis (t2) by using multivariate regression analyses.ResultsA total of 502 patients (74.7% women) participated in both measurements. Mean work ability increased significantly from t1 (6.0; SD = 2.3) to t2 (6.8; SD = 2.2) (t = −9.3; p < 0.001). As many as 380 (76%) AYA cancer survivors reported reduced work ability at t1; 1 year later, this still applied to 287 (57%) of them. Decreased work ability (t2) was associated with more cognitive impairment, higher effort coping with the disease, comorbidities, sick leave > 6 months (since diagnosis), and having children (adj R2 = .48). Cognitive impairments occurred in approximately every fifth patient at both surveys.ConclusionsAchieving maximum work ability is a major challenge for AYAs. Our results show the need for multimodal cancer survivorship and rehabilitation programmes with a special focus on improving cognitive and psychosocial functioning.Implications for Cancer SurvivorsAYAs with cancer should receive targeted occupational counselling early in the course of the disease.

Incidence of germline variants in Lynch syndrome-related genes among Japanese endometrial cancer patients aged 40years or younger.

[Objective] Lynch syndrome (LS) is an autosomal dominant inherited disorder caused by a germline pathogenic variant in DNA mismatch repair (MMR) genes. Endometrial cancer frequently precedes another LS-associated tumor. This study aimed to clarify the incidence and features of LS in young Japanese endometrial cancer patients.[Methods] Sixty-five patients aged 40years or younger, who were diagnosed with endometrial cancer, were enrolled in this study. Targeted sequencing of a hereditary colorectal cancer-related gene panel including the MMR genes MLH1, MSH2, MSH6, and PMS2 was conducted on DNA samples extracted from blood cells.[Results] Overall, 6 missense variants (2 in MSH2, 2 in MSH6, and 2 in PMS2), 1 inframe deletion variant in MSH2, 1 splice variant in MSH2, and 1 two-base substitution in the 3' untranslated region in MLH1 were detected in 9 (13.8%) patients. Among these, the splice variant c.1276G > T (p.Ile411_Gly426del16) in MSH2 was annotated as pathogenic, while other variants were of uncertain significance. The patient with the pathogenic variant had a family history of endometrial and colorectal cancer and was diagnosed with endometrial cancer at age 35.[Conclusion] The incidence of LS among Japanese endometrial cancer patients of reproductive age (≤ 40years) in this study was at least 1.5%; however, 12.3% of patients had variants of uncertain significance in MMR genes.

The impact of socio-demographic factors on the survival of cancer patients in Zimbabwe

We provide a survival analysis of cancer patients in Zimbabwe. Our results show that young cancer patients have lower but not significant hazard rate compared to old cancer patients. Male cancer patients have lower but not significant hazard rate compared to female cancer patients. Race and marital status are significant risk factors for cancer patients in Zimbabwe.

Clinical characteristics of renal cell carcinoma in patients under the age of 40

BackgroundRenal cell carcinoma (RCC) most commonly afflicts older patients while those 40 years old or younger represent an uncommon population. We aim to describe the tumor characteristics and treatment patterns for young kidney cancer patients utilizing the National Cancer Database. MethodsThe National Cancer Database Participant User File for RCC was queried from 2004 to 2016. Demographics and treatment trends were analyzed and compared between a young cohort, those aged 40 and younger vs. a conventional cohort, those older than 40. Pathology analyzed included clear cell, papillary, chromophobe, RCC not otherwise specified, and miscellaneous uncategorized. Subanalysis was performed for patients with localized disease and treatment type. ResultsAmongst the 514,879 patients diagnosed with RCC, 4.7% were ≤40 years old. RCC for individuals ≤40 has a higher proportion of female gender, non-Caucasian race, and chromophobe pathology, relative to the conventional cohort. Younger patients more often presented with cT1 disease with decreased rates of metastasis. Risk of 30-day readmission after surgery was similar between cohorts. For patients with cT1-2N0M0 disease, there was a decreasing rate of radical nephrectomy and increasing rate of partial nephrectomy; however, the conventional cohort had an increasing rate of percutaneous ablation while this remained stable in the younger cohort. ConclusionYoung RCC patients had a higher proportion of female gender, chromophobe histology, and favorable tumor characteristics. Partial nephrectomy has seen a dramatic increase in application regardless of age while percutaneous ablation increased only in the conventional cohort.