Time to Chemotherapy and Oncofertility Counseling in Pediatric Hematology/Oncology Patients: A Single Center Retrospective Review

Time to Chemotherapy and Oncofertility Counseling in Pediatric Hematology/Oncology Patients: A Single Center Retrospective Review | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 8 May 2025 V1 Latest version Share on Time to Chemotherapy and Oncofertility Counseling in Pediatric Hematology/Oncology Patients: A Single Center Retrospective Review Authors : John Mariano 0000-0001-9908-5128 [email protected] , Hayley Flanagan 0009-0004-2423-0182 , Kimberly Seymour H , Nicole SanGiacomo , Nneka Ogbutor , Arman Niknafs , Brittany Hodges , Adam Evans , Andrea Baran , and Jeffrey Andolina 0000-0001-6502-6859 Authors Info & Affiliations https://doi.org/10.22541/au.174668975.53823254/v1 Published Frontiers in Oncology Version of record Peer review timeline 272 views 164 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background American Society of Reproductive Medicine and American Society of Clinical Oncology emphasize the importance oncofertility counseling. Survivors often report inadequate attention to this crucial aspect of care. Balancing timely treatment initiation with oncofertility counseling presents challenges including cost, age at diagnosis, information overload, and time constraints. Procedures We performed chart abstraction of 265 pediatric patients diagnosed at University of Rochester Medical Center (January 1 st 2015 - May 31 st 2022). Hematologic malignancies made up 37.65% of the population. Median age was 7 with male predominance (56.2%). The majority of patients were Caucasian (80.7%). Results Only 12.5 % of the population had an oncofertility visit with reproductive endocrinology or urology and 42.4% had documented counseling with their oncology team. Sexual health was discussed in 2.6% of patients and 12.1% of patients had documented Tanner staging. Hematologic malignancy patients had a lower time to therapy (4.2 days) compared to extracranial solid tumors (14.8 days) and CNS tumors (97.8 days) when outliers were removed. Longer time to therapy trended towards significance for oncofertility visits and there was no statistical difference in oncofertility vists or primary team counseling rates based on disease severity. Conclusions The time before chemotherapy initiation is a unique barrier to oncofertility counseling for pediatric patients with malignancy. While most patients will have retained fertility on current protocols, patients with high risk of relapse will receive therapy more likely to threaten fertility. The results of this study indicate targeted intervention prior to relapse for this population may be a more feasible approach. Title Page: Time to Chemotherapy and Oncofertility Counseling in Pediatric Hematology/Oncology Patients: A Single Center Retrospective Review John Mariano, MD 1 , Hayley Brianne Flanagan, MD 1 , Kimberly H Seymour, MD, MS 1 , Nicole SanGiacomo, CPNP-AC, MSN, RN, CPHON 1 , Nneka Ogbutor, MD 1 , Arman Niknafs, BSc 1 , Brittany Hodges, BA 1 , Adam Evans, MD 1 , Andrea Baran, MS 1 and Jeffrey R. Andolina, MD, MS 1 1 University of Rochester Medical Center, Rochester, NY Corresponding author: Name: John Mariano Phone: (585) – 507- 6289 Email: [email protected] Word Count for: a) Abstract: 249 words (Max 250 words) b) Main Text (excludes title page, abstract, Conflicts of Interest, Acknowledgments, References, Tables, Figures, and Legends): Max 3500 words The number of Tables, Figures, and Supporting Information files: 5 tables and 1 figure (Max 7) A short running title (not to exceed 50 characters): Time to Chemotherapy and Oncofertility Counseling Three to six keywords to index the content: Oncofertility, Chemotherapy, Barriers Abbreviations Key: Published Abstracts: The 16th Annual Conference of the Oncofertility Consortium 2024 “Time to Chemotherapy Initiation is a Barrier to Oncofertility Counseling in Pediatric Cancer Patients” John Mariano, MD 1 ; Hayley Flanagan, MD 1 ; Kimberly Seymour, MD 1 ; Nicole SanGiacomo, CPNP-AC, MSN, RN, CPHON 1 ; ; Nneka Ogbutor, MD 1 ; Arman Niknafs, BSc 1 , Brittany Hodges, BA 1 , Adam Evans, MD 1 ; Jeffery Andolina, MD 1 1 University of Rochester, Wilmot Cancer Institute, University of Rochester Medical Center American Society of Hematology Annual Meeting 2023 “ Time to Chemotherapy Initiation is a Barrier to Oncofertility Counseling in Pediatric Hematologic Malignancies” John Mariano, MD 1 ; Hayley Flanagan, MD 1 ; Kimberly Seymour, MD 1 ; Nicole SanGiacomo, CPNP-AC, MSN, RN, CPHON 1 ; ; Nneka Ogbutor, MD 1 ; Arman Niknafs, BSc 1 , Brittany Hodges, BA 1 , Adam Evans, MD 1 ; Jeffery Andolina, MD 1 1 University of Rochester Medical Center Time to Chemotherapy and Oncofertility Counseling in Pediatric Hematology/Oncology Patients: A Single Center Retrospective Review John Mariano, MD 1 , Hayley Brianne Flanagan, MD 1 , Kimberly H Seymour, MD, MS 1 , Nicole SanGiacomo, CPNP-AC, MSN, RN, CPHON 1 , Nneka Ogbutor, MD 1 , Arman Niknafs, BSc 1 , Brittany Hodges, BA 1 , Adam Evans, MD 1 , Andrea Baran 1 and Jeffrey R. Andolina, MD, MS 1 1 University of Rochester Medical Center, Rochester, NY Background American Society of Reproductive Medicine and American Society of Clinical Oncology emphasize the importance oncofertility counseling. Survivors often report inadequate attention to this crucial aspect of care. Balancing timely treatment initiation with oncofertility counseling presents challenges including cost, age at diagnosis, information overload, and time constraints. Procedures We performed chart abstraction of 265 pediatric patients diagnosed at University of Rochester Medical Center (January 1 st 2015 - May 31 st 2022). Hematologic malignancies made up 37.65% of the population. Median age was 7 with male predominance (56.2%). The majority of patients were Caucasian (80.7%). Results Only 12.5 % of the population had an oncofertility visit with reproductive endocrinology or urology and 42.4% had documented counseling with their oncology team. Sexual health was discussed in 2.6% of patients and 12.1% of patients had documented Tanner staging. Hematologic malignancy patients had a lower time to therapy (4.2 days) compared to extracranial solid tumors (14.8 days) and CNS tumors (97.8 days) when outliers were removed. Longer time to therapy trended towards significance for oncofertility visits and there was no statistical difference in oncofertility vists or primary team counseling rates based on disease severity. Conclusions The time before chemotherapy initiation is a unique barrier to oncofertility counseling for pediatric patients with malignancy. While most patients will have retained fertility on current protocols, patients with high risk of relapse will receive therapy more likely to threaten fertility. The results of this study indicate targeted intervention prior to relapse for this population may be a more feasible approach. Time to Chemotherapy and Oncofertility Counseling in Pediatric Hematology/Oncology Patients: A Single Center Retrospective Review John Mariano, MD 1 , Hayley Brianne Flanagan, MD 1 , Kimberly H Seymour, MD, MS 1 , Nicole SanGiacomo, CPNP-AC, MSN, RN, CPHON 1 , Nneka Ogbutor, MD 1 , Arman Niknafs, BSc 1 , Brittany Hodges, BA 1 , Adam Evans, MD 1 , Andrea Baran, MS 1 and Jeffrey R. Andolina, MD, MS 1 1 University of Rochester Medical Center, Rochester, NY Introduction: The American Society of Clinical Oncology (ASCO) clinical practice guidelines recommend standardized fertility counseling for all adult and pediatric patients as soon as possible before receiving anticancer therapy to maximize options for fertility preservation 1 . The American Society for Reproductive Medicine recommends programmatic requirements for comprehensive fertility preservation care including rapid access, an interdisciplinary and collaborative medical team, and specific baseline laboratory testing 2 . While these recommendations apply to both pediatric and adult patients, pediatric patients have a very specific set of challenges that make fertility preservation and sexual health care challenging. Barriers to appropriate fertility preservation care in pediatric patients include high pressure to initiate therapy rapidly, potential financial expense for families, variable fertility preservation options in pre-pubescent vs. post-pubescent patients, need for counseling tailored to varying developmental stages, and the need for coordination around sedated baseline procedures (central line placement, echocardiogram, imaging, biopsies, lumbar punctures, etc). Since the Research and Care Imperatives for Adolescents and Young Adults with Cancer Progress Review Group identified care gaps in adolescent and young adult patients with cancer in 2006, there has been abundant literature investigating fertility preservation in this population 3 . Many targeted cross-sectional or retrospective analyses have investigated specific populations restricted by age, gender, or disease type, as summarized by Flink et al 4 . While a number of these studies have estimated the prevalence of fertility counseling and/or successful preservation among patients receiving gonadotoxic therapies, many were limited by sample selection (i.e., gender, age, disease type, etc.) 5 - 13 . Other studies have sought to assess the perspective of cancer survivors, who often report limited or ineffective pre-treatment fertility counseling despite their expressed desire for more dedicated support in this area 14 – 20 . Despite potential for recall bias and loss to follow up impacting these findings, these qualitative data indicate an area of supportive oncologic care in need of improvement. Notably, while patients recognize the importance of fertility preservation discussions, as evidenced by a group of adolescent female cancer survivors who indicated interest in treatments to help preserve fertility when feasible, these patients also expressed a lack of willingness to postpone cancer therapy 21 . Most oncologists also appreciate the need for fertility preservation counseling and management. However, many report feeling underequipped to do so due to lack of education and/or formalized resources 22 – 25 . Numerous single-institution reports have highlighted the benefits of standardized oncofertility programs. These studies have measured improvement in documentation of fertility discussions, referrals placed for fertility services, and ultimate pursuit of fertility preservation in pediatric or young adult patients 26 – 32 . Methods: We conducted a retrospective review of Pediatric Hematology/Oncology patients at the University of Rochester Medical Center from January 1 st 2015 – and May 31 st 2022 using manual chart abstraction. Electronic medical record data was collected with the following variables: Demographic information (age, gender, race, ethnicity, zip code); Diagnosis; Date of pathologic diagnosis; Date of systemic chemotherapy initiation; Disease risk factors (Stage, Risk Stratification, Etc); Oncofertility documentation by treating oncologist; Oncofertility documentation from fertility provider; and Tanner Staging. Statistical Analysis: Patient and disease characteristics were summarized using medians for continuous variables, and counts and proportions for categorical variables. Time to therapy was calculated in days from the date of diagnosis to the date of systemic chemotherapy initiation, and summarized using median within diagnosis group. Fertility counseling outcomes were summarized using counts and proportions, overall and within diagnosis group. Multivariate logistic regression was used to assess the association of time to therapy, age, patient sex and disease risk with the fertility counseling outcomes. All p-values are two-sided, and all hypothesis tests were conducted at the 0.05 level of significance. SAS v9.4 (SAS Institute, Inc., Cary, NC, USA) was used for all analyses. Results: Hematologic malignancies comprised 37.65% of the cohort, with acute lymphoblastic leukemia (15.43%) and acute myeloid leukemia (7.72%) being the most prevalent. The median age was 7, with a male predominance (56.2%). Patients were predominantly Caucasian (80.6%) (Tables 1 and 2). Hematologic malignancy patients generally had a shorter time between pathologic diagnosis and treatment initiation (14.4 days) compared to extracranial solid tumors (14.8 days) and CNS tumors (97.8 days). When outliers such as nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and B-cell lymphoblastic lymphoma were removed from the hematologic malignancy group, this interval was shortened even further to 4.2 days (Table 3). Additionally, diagnoses that generally require an immediate inpatient admission for treatment initiation following diagnosis such as acute leukemia and Burkitt lymphoma had an expectedly very short (1-4 days) time to therapy while those diagnosed and treated primarily in the outpatient setting such as sarcomas or Hodgkin lymphoma had a less acute initiation of therapy (7 – 20 days). Given a number of CNS tumors may have had periods of post-operative monitoring or observation prior to therapy initiation, these patients’ protracted period prior to therapy initiation correlated as expected to disease course. With respect to oncofertility outcomes, only 12.5% of the patient population saw reproductive endocrinology or urology for an oncofertility visit and 42.4% had documented oncofertility discussions with their oncology team not including consent forms which were not universally readily available. Sexual health was discussed in only 2.6% of patients, and only 12.1% of patients had documented Tanner staging before treatment initiation (data not shown). These rates did however increase in the populations with a median age at diagnosis that typically occurs in the adolescent and young adult range defined by the World Health Organization of 15 to 39 years old. For example, oncofertility visits and primary team oncofertility discussions were relatively high in Hodgkin lymphoma (42.9% and 53.8%), diffuse large B-cell lymphoma (40.0% and 60.0%), and germ cell tumors (70% and 50%) (Table 4), all of which are more commonly diagnosed in adolescent and young adult populations. Adjusted for age, gender and disease risk, time to therapy trended towards significance for oncofertility outcomes both in terms of oncofertility specialist visits and primary team oncofertility counseling. Interestingly, these rates trended inversely in that a longer time to therapy led to increased odds of an oncofertility visit while a shorter time to therapy led to decreased odds of primary team oncofertility counseling. There was insufficient evidence of an association of disease risk and patient sex with either outcome. The only factor that was significantly associated with counseling outcome was older age at diagnosis. with an adjusted OR of 1.28 (p for oncofertility subspecialist visits and primary team oncofertility counseling respectively Discussion: Barriers to oncofertility care have been extensively described since the identification of this supportive care need in the oncologic population. While the narrow time window prior to therapy initiation is often cited, the specific effects of time to chemotherapy initiation have not been studied in depth. In this study, we provide a retrospective assessment of time to chemotherapy initiation and oncofertility counseling in a medium sized pediatric hematology/oncology center. This study provides a foundational basis for the real-world assessment of these measures considering there is no formal oncofertility structure currently in place at this center. It confirms that providers instinctively tend to counsel and refer post-pubescent patients despite guidelines indicating this should be universally applied across the age spectrum. In part this is likely due to the more limited and often more invasive options for fertility preservation that are available for pre-pubescent patients 33 . Additionally, it highlights the need for a standardized approach to oncofertility counseling and documentation by the primary oncology team to meet the goal of ensuring all patients receive adequate and appropriate information prior to chemotherapy initiation. Because potential infertility risk was not readily available for this population, we used disease risk severity as a potential marker not only for upfront therapy intensity but for the potential for disease recurrence which often leads to much more intensive therapy in the pediatric oncology landscape. We did not see that disease severity had any impact on rates of oncofertility counseling or subspecialist referral. Importantly, this data was inclusive of the survivorship period, so this care gap occurred not only prior to initial therapy but potentially within the window of remission. This is of particular importance for patients with hematologic malignancies in which frontline therapy itself may not result in infertility or sexual health disruption whereas second line therapy, particularly if including allogenic stem cell transplant, would be very likely to do so. This highlights another layer of need in oncofertility standardization that extended from upfront counseling to continued monitoring and revisited assessment during the survivorship period. This study has a number of limitations including the retrospective design, lack of longitudinal fertility preservation outcomes, and lack of specific details regarding infertility risk of therapy. Additionally, the assessment was limited to the electronic medical record assessment and did not include potential other areas of documentation of oncofertility discussions such as chemotherapy consents. In conclusion, this is the first study to characterize the relationship of time to therapy and oncofertility outcomes. It can serve as a foundation for prospective interventional studies aimed at instituting a standardized operating procedure both for upfront oncofertility counseling and referral as well as longitudinal oncofertility counseling during survivorship. Additionally, it highlights a key area of need in the pre-pubescent population with an achievable goal of improving counseling despite the challenges of fertility preservation in this population. Conflict of Interests: The authors have no conflicts of interest to report. Acknowledgments: We would like to acknowledge Andrea Baran for providing the statistical support for this study. REFERENCES 1. Fertility Preservation in Patients With Cancer: ASCO Clinical Practice Guideline Update Kutluk Oktay, Brittany E. Harvey, Ann H. Partridge, Gwendolyn P. Quinn, Joyce Reinecke, Hugh S. Taylor, W. Hamish Wallace, Erica T. Wang, and Alison W. Loren. Journal of Clinical Oncology 2018 36:19, 1994-2001 2. Dina M. Flink, Jeanelle Sheeder, and Laxmi A. 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Information & Authors Information Version history V1 Version 1 08 May 2025 Peer review timeline Published Frontiers in Oncology Version of Record 11 May 2026 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords all aml brain tumors chemotherapy endocrinology long term survival sarcoma Authors Affiliations John Mariano 0000-0001-9908-5128 [email protected] University of Rochester Medical Center View all articles by this author Hayley Flanagan 0009-0004-2423-0182 University of Rochester Medical Center View all articles by this author Kimberly Seymour H University of Rochester Medical Center View all articles by this author Nicole SanGiacomo University of Rochester Medical Center View all articles by this author Nneka Ogbutor University of Rochester Medical Center View all articles by this author Arman Niknafs University of Rochester Medical Center View all articles by this author Brittany Hodges University of Rochester Medical Center View all articles by this author Adam Evans University of Rochester Medical Center View all articles by this author Andrea Baran University of Rochester Medical Center View all articles by this author Jeffrey Andolina 0000-0001-6502-6859 University of Rochester Medical Center View all articles by this author Metrics & Citations Metrics Article Usage 272 views 164 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation John Mariano, Hayley Flanagan, Kimberly Seymour H, et al. 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