Treatment-related Sequelae Research Articles

Quality of life in patients with skull base meningiomas treated with microsurgery: a prospective observational study.

Skull base meningiomas are chronic conditions that can present with a wide variety of symptoms ranging from near normalcy to chronic and prolonged disability and also often worsen by treatment-related sequelae. Hence, it is necessary to investigate the quality of life (QOL) among patients with skull base meningioma and evaluate the impact of microsurgery on their overall well-being. In this prospective observational study, 36 patients undergoing microsurgery for skull base meningioma were assessed for QOL using SF-36 questionnaires. Results were compared to the QOL of 36 patients with a non-neurosurgical chronic disease (diabetes mellitus) and 36 matched healthy volunteers. This study commenced from 2019 and ended in 2022. All QOL parameters in skull base meningioma patients were preoperatively significantly worse than in the healthy population. The most affected QOL domain were role limitation due to physical health (RLPH) and role limitation due to emotional problems (RLEP). Within one year after surgery, skull base meningioma patients showed a significant improvement of all QOL parameters. The domains of physical functioning (PF), emotional well-being (EWB), body pain (BP) and general health (GH) improved to similar values as their matched healthy controls. However, social functioning (SF), RLPH, and RLPE remained still significantly affected. Compared to chronic diabetic patients, the domains PF, EWB, BP, and GH showed significantly better QOL values after one year in skull base meningioma patients, but RLEP and RLPH were worse. Microsurgery can significantly improve all QOL domains in skull base meningioma patients within one year. Physical activity, overall health, and mental well-being have been observed to return to even normal levels. While certain QOL domains may still be affected post-microsurgery, it is evident that microsurgery can yield a substantial improvement, ultimately raising QOL to levels surpassing those seen in other non-neurosurgical chronic diseases, such as diabetes mellitus.

Feasibility Study of Adverse Childhood Experiences, Treatment-Related Sequelae, and Inflammatory Markers in Breast Cancer Survivors.

To explore the incidence of adverse childhood experiences (ACEs) in breast cancer survivors and potential associations with long-term treatment-related sequelae. English-speaking breast cancer survivors three or more years from diagnosis with complete treatment response (N = 120) were recruited prior to scheduled survivorship clinic visits. Participants in this cross-sectional observational feasibility study rated anxiety, depression, fatigue, sleep disturbance, cognitive issues, resilience, and ACEs (experienced prior to age 18 years). Blood samples were analyzed for inflammatory and epigenetic biomarkers. ACEs assessment was feasible. Higher ACE scores correlated with greater fatigue, anxiety, and depression, and with lower cognitive function (p < 0.05). Resilience was positively associated with cognitive function and negatively associated with fatigue, anxiety, and depression. There is evidence for the impact of ACEs on long-term treatment-related sequelae in women with breast cancer. Oncology nurses should consider incorporating ACEs assessment into the workflow for women receiving survivorship care.

Neuropsychological task outcomes among survivors of childhood acute lymphoblastic leukemia in Malaysia

This study intended to explore the neuropsychological ramifications in childhood acute lymphoblastic leukemia (ALL) survivors in Malaysia and to examine treatment-related sequelae. A case-control study was conducted over a 2-year period. Seventy-one survivors of childhood ALL who had completed treatment for a minimum of 1 year and were in remission, and 71 healthy volunteers were enlisted. To assess alertness (processing speed) and essential executive functioning skills such as working memory capacity, inhibition, cognitive flexibility, and sustained attention, seven measures from the Amsterdam Neuropsychological Tasks (ANT) program were chosen. Main outcome measures were speed, stability and accuracy of responses. Mean age at diagnosis was 4.50 years (SD ± 2.40) while mean age at study entry was 12.18 years (SD ± 3.14). Survivors of childhood ALL underperformed on 6 out of 7 ANT tasks, indicating poorer sustained attention, working memory capacity, executive visuomotor control, and cognitive flexibility. Duration of treatment, age at diagnosis, gender, and cumulative doses of chemotherapy were not found to correlate with any of the neuropsychological outcome measures. Childhood ALL survivors in our center demonstrated significantly poorer neuropsychological status compared to healthy controls.

Physiotherapy management of breast cancer treatment-related sequelae

Physiotherapy management of breast cancer treatment-related sequelae

Dyadic Yoga for Head and Neck Cancer Patients Undergoing Chemoradiation and their Family Caregivers

ObjectivesConcurrent chemoradiation to treat head and neck cancer (HNC) may result in debilitating toxicities. Targeted exercise such as yoga therapy may buffer against treatment-related sequelae; thus, this pilot RCT examined the feasibility and preliminary efficacy of a yoga intervention. Because family caregivers report low caregiving efficacy and elevated levels of distress, we included them in this trial as active study participants. MethodsHNC patients and their caregivers were randomized to a 15-session dyadic yoga program or a waitlist control (WLC) group. Prior to randomization, patients completed standard symptom (MDASI-HN) and patients and caregivers completed quality of life (SF-36) assessments. The 15-session program was delivered parallel to patients’ treatment schedules. Participants were re-assessed at patients’ last day of chemoradiation and again 30 days later. Patients’ emergency department visits, unplanned hospital admissions and gastric feeding tube placements were recorded over the treatment course and up to 30 days later. ResultsWith a consent rate of 76%, 37 dyads were randomized. Participants in the yoga group completed a mean of 12.5 sessions and rated the program as “beneficial.” Patients in the yoga group had clinically significantly less symptom interference and HNC symptom severity and better QOL than those in the WLC group. They were also less likely to have a hospital admission (OR = 3.00), emergency department visit (OR = 2.14), and/or a feeding tube placement (OR = 1.78). ConclusionYoga therapy appears to be a feasible, acceptable, and possibly efficacious behavioral supportive care strategy for HNC patients undergoing chemoradiation. A larger efficacy trial is warranted.

Yoga-based supportive care for patients with head and neck cancer undergoing radiotherapy: Results of a three-arm randomized controlled trial.

292 Background: Radiotherapy (RT) to treat head and neck cancer (HNC) may result in debilitating toxicities and functional problems. Targeted yoga therapy delivered concurrently to RT may buffer against treatment-related sequelae. Given the high distress rates in spouses and interdependence of distress in couples, involving a spousal caregiver in the intervention may have additional benefits. Thus, we randomized patient-caregiver dyads to either a dyadic yoga (DY), patient yoga (PY) or usual care (UC) control arm. We hypothesized that both yoga arms are better than the UC arm regarding functional outcomes and healthcare utilization (i.e., feeding tube (FT) placements, emergency department (ED) and hospital admissions (HA) across the standard RT period. The comparison between the DY vs PY group was considered exploratory. Methods: HNC patients planned to receive ≥25 fractions of RT and their caregivers completed baseline assessments and were then randomized to the DY, PY or UC arm. Both yoga programs consisted of 15 sessions delivered parallel to the RT schedule. Sessions were either in person or via videoconference. Patients completed the self-report part of the PG-SGA on a weekly basis during the RT period (5-6 weeks). We extracted FT, ED and HA as healthcare utilization metrics from patients’ electronic medical records as binary variables (yes/no). Results: 100 patients (mean age: 60.3 yrs., 85% male, 79% NHW, 67% early stage, 54% chemo-RT) and caregivers (mean age: 54.9 yrs., 83% female, 78% NHW) were randomized (DY: n=34; PY: n=33, UC: n=33). Session attendance was high for both yoga arms (88% attended ≥ 10 session) with mean of 13.13 sessions in the DY and 13.30 sessions in the PY group. Intent to treat analyses using multi-level modeling controlling for patient age, sex, disease stage and treatment (RT vs CRT) revealed a significant effect between the DY and UC group for the physical function (F=5.27, p=.03) and the nutrition intake (F=4.97, p=.03) PG-SGA subscales favoring the DY group. The other comparisons (PY vs UC and DY vs PY) were not significant. None of the comparisons for the symptom and weight subscales were significant. Logistic regression analyses revealed a significant effect for FT placement so that both DY (p=.05) and PY (p=.02) groups had significantly fewer FTs than the UC group. The effect for ED visits was marginally significant and the effect for HA was not significant. Conclusions: Yoga therapy, particularly when delivered to patient-caregiver dyads, appears to be a beneficial behavioral supportive care strategy for HNC patients undergoing RT. We revealed significantly improved physical function and nutrition intake and fewer FTs relative to a UC comparison group. A larger comparative effectiveness trial is warranted. Clinical trial information: NCT04607590 .

CE Workshop 07: Cognitive Effects of Cancer and Treatment: “Chemobrain” and Beyond

Abstract &amp; Learning Objectives:Improvements in treatment for non-CNS cancer have greatly improved survivorship, allowing increased attention to cancer- and treatment-related sequelae. Cognitive symptoms (cancer-related cognitive impairment, or CRCI) are reported by a large percentage of cancer survivors, and can have a clinically meaningful impact on educational, vocational, and social functioning, and thus overall quality of life. Better understanding of these concerns is therefore of critical importance, and is needed to guide treatment and potential prevention strategies. Neuropsychological studies over the past 40 years have demonstrated cognitive domains commonly affected in cancer patients treated with chemotherapy, but have also shown cognitive differences in patients not treated with systemic therapy and those receiving other types of treatment (e.g., hormonal therapies) relative to non-cancer control groups. More recently, structural and functional neuroimaging research has added to our understanding of the neural substrate of these cognitive symptoms. This course will describe various neuroimaging modalities used to investigate CRCI, including examination of grey and white matter volume and structural integrity, blood flow, brain activation during cognitive processing and at rest, and structural and functional connectivity. The presentation will also review how neuroimaging findings relate to objective and self-reported cognition and clinical and treatment factors, and discuss potential approaches currently being investigated to treat CRCI. Upon conclusion of this course, learners will be able to:1.Explain commonly affected cognitive domains after non-CNS cancer and treatment2.Discuss structural and functional brain changes related to cancer, chemotherapy, and other treatments3.Describe treatment interventions being investigated to treat cancer- and treatment-related cognitive symptoms.

Understanding advanced practice registered nurse perspectives on providing care to people with a history of breast cancer.

People with a history of breast cancer (PHBC) face a lifelong risk of treatment-related sequelae affecting their quality of life. Stakeholders advocate for improving breast cancer survivorship outcomes by increasing clinicians' knowledge of cancer survivorship issues. In Missouri, advanced practice registered nurses (APRNs) in nononcology settings provide routine survivorship care to PHBC; however, little is known about how they approach survivorship care planning for PHBC. Examine perspectives of Missouri APRNs practicing in nononcology settings about providing survivorship care to PHBC. A combination of grounded theory and thematic analysis techniques was used for focus groups and semistructured interviews. The interviews were audio-recorded, transcribed, and analyzed using grounded theory coding methods. Nineteen nononcology Missouri-based APRNs (18 NPs, 1 CNS/DNP) shared their perspectives about managing care for PHBC. We identified four major themes. Our participants (1) attuned their baseline assessment techniques to a history of breast cancer; (2) were prepared to order additional evaluations; (3) were willing to proactively figure out next best steps for PHBC beyond theneed for breast cancer recurrence surveillance; and (4) suggest that streamlining cancer survivorship care resources would benefit both clinicians and PHBC. Our findings shed light on how APRNs approach care planning for PHBC and the needs of nononcology APRNs for managing PHBC. Advanced practice registered nurses are well-positioned to improve cancer survivorship care. Increasing knowledge of cancer survivorship care guidelines could improve long-term health outcomes of PHBC. Access to cancer survivorship resources or experts via telehealth/technology for both APRNs and patients could improve survivorship care and overall health of PHBC.

Dissecting the prognostic role of baseline body mass index (BMI) in early breast cancer (BC): Individual patient-level analysis from five mammella interGruppo (MIG) and gruppo italiano mammella (GIM) randomized clinical trials (RCTs).

12067 Background: Nearly half of patients (pts) are overweight or obese at BC diagnosis (dx). Higher BMI at dx has been associated with cardiometabolic comorbidities, higher risk of severe treatment-related sequelae, and worse quality of life. Previous studies showed inferior survival outcomes among patients with early BC and high BMI, although not consistently. The aim of this study was to explore the prognostic role of BMI at dx using data from five RCTs of adjuvant therapy for early stage BC with long-term follow-up. Methods: Pts with known BMI at dx, randomized in the MIG-1, MIG-5, GIM-2, GIM-3 and GIM-6 phase III RCTs were included. BMI was categorized as lean ( &lt; 25 kg/m2), overweight (25-30 kg/m2) or obese (≥ 30 kg/m2). Outcomes included disease-free survival (DFS), breast cancer free-interval (BCFI) and overall survival (OS). Survival estimates were compared using the Kaplan-Meier method and log-rank test. Multivariable Cox proportional hazard models stratified by trial and relevant prognostic factors assessed associations between BMI and outcomes. Results: Among 7334 pts in the overall population, mean age was 56.4 years (SD 11.2), 67.8% had node-positive disease, 76.9% received chemotherapy and 83.0% endocrine therapy. Most pts were overweight (33.1%) or obese (21.0%) and 45.9% were lean. Higher BMI was associated with older age, larger tumor size, higher nodal status, and HR+/HER2- subtype. At a median follow-up of 10.0 years (IQR 6.1-15.1) there were 2165 DFS, 1674 BCFI and 1354 OS events. Pts with higher BMI had worse DFS and OS (log-rank p = 0.007 and p &lt; .0001, respectively), but similar BCFI (p = 0.48). BMI at dx was an independent risk factor for worse OS, but not for DFS and BCFI (Table). Results in the HR+/HER2- population (n = 4093) were consistent: pts with higher BMI had worse DFS, BCFI, and OS (log-rank p = 0.001, p &lt; .006, and p &lt; .0001, respectively) and BMI at dx was an independent risk factor only for worse OS (aHR [95%CI] 1.06 [0.84-1.32] and 1.31 [1.02-1.67] for overweight and obese vs lean pts, respectively). Conclusions: In this large study of pts with early BC treated in RCTs with long-term follow-up, higher BMI at dx was an independent risk factor for overall mortality but not for BC-specific outcomes. Weight loss interventions may mitigate the detrimental effect of excess body weight on outcomes of BC survivors, including by reducing the burden and risks of associated cardiometabolic comorbidities. [Table: see text]

Smaller cornu ammonis (CA3) as a potential risk factor for suicidal behavior in mood disorders

Mood disorders and suicidal behavior have moderate heritability and familial transmission, and are associated with smaller hippocampal volumes. However, it is unclear whether hippocampal alterations reflect heritable risk or epigenetic effects of childhood adversity, compensatory mechanisms, illness-related changes, or treatment effects. We sought to separate the relationships of hippocampal substructure volumes to mood disorder, suicidal behavior, and risk and resilience to both by examining high familial risk individuals (HR) who have passed the age of greatest risk for psychopathology onset. Structural brain imaging and hippocampal substructure segmentation quantified Cornu Ammonis (CA1-4), dentate gyrus, and subiculum gray matter volumes in healthy volunteers (HV, N = 25) and three groups with one or more relatives reporting early-onset mood disorder and suicide attempt: 1. Unaffected HR (N = 20); 2. HR with lifetime mood disorder and no suicide attempt (HR-MOOD, N = 25); and 3. HR with lifetime mood disorder and a previous suicide attempt (HR-MOOD + SA, N = 18). Findings were tested in an independent cohort not selected for family history (HV, N = 47; MOOD, N = 44; and MOOD + SA, N = 21). Lower CA3 volume was found in HR (vs. HV), consistent with the direction of previously published findings in MOOD+SA (vs. HV and MOOD), suggesting the finding reflects a familial biological risk marker, not illness or treatment-related sequelae, of suicidal behavior and mood disorder. Familial suicide risk may be mediated in part by smaller CA3 volume. The structure may serve as a risk indicator and therapeutic target for suicide prevention strategies in high-risk families.

The Potential of Proton Therapy for Locally Advanced Breast Cancer: Clinical and Technical Considerations

Proton therapy is a promising therapeutic modality with unique physical properties that allow for abrupt dose fall-off distal to the target of interest, thereby sparing nearby organs at risk. A number of studies have identified the utility of proton radiation in mitigating treatment related sequelae for patients with locally advanced breast cancers. Thus, in the following review, we highlight clinical and technical considerations for proton radiotherapy delivery in patients with locally advanced breast cancer.

Radiotherapy with Helium Ions Has the Potential to Improve Both Endocrine and Neurocognitive Outcome in Pediatric Patients with Ependymoma

Ependymomas are the third most-frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Compared to photon radiation treatment, proton therapy often achieves even better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions could further reduce side effects, providing better protection of healthy tissue despite similar target coverage. In our in silico study, 15 pediatric ependymoma patients were considered. All patients underwent adjuvant radiotherapeutic treatment with active-scanned protons at Heidelberg Ion Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric advantage of ion beam therapy compared to the current state-of-the-art photon-based treatments. To estimate the potential clinical benefit of helium ions, normal tissue complication probabilities (NTCP) were calculated. Target coverage was comparable in all three modalities. As expected, the integral dose absorbed by healthy brain tissue could be significantly reduced with protons by up to -48% vs. IMRT. Even compared to actively scanned protons, relative dose reductions for critical neuronal structures of up to another -39% were achieved when using helium ions. The dose distribution of helium ions is significantly superior when compared to proton therapy and IMRT due to the improved sparing of OAR. In fact, previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose-response relationship of critical organs at risk combined with NTCP calculation, the results of our study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

Management of treatment-related sequelae following colorectal cancer.

Colorectal cancer survivors are one of the most rapidly growing groups of patients living with and beyond cancer. In a national multidisciplinary setting, we have examined the extent of late treatment-related sequelae in colorectal cancer survivors and present the scientific evidence for management of these conditions in this patient category with the aim of facilitating identification and treatment. A systematic search for existing guidelines and relevant studies was performed across 16 and 4 databases, respectively, from inception to 2021. This yielded 13 guidelines and 886 abstracts, of which 188 were included in the finalized guideline (231 included for full text review). Secondarily, bibliographies were cross-referenced and 53 additional articles were included. Symptoms have been divided into overall categories including psychosocial, bowel-related, urinary, sexual (male and female), pain/neuropathy and fatigue symptoms or complaints that are examined individually. Merging and grading of data resulted in 22 recommendations and 42 management strategies across categories. Recommendations are of a more general character, whereas management strategies provide more practical advice suited for initiation on site before referral to specialized units. Treatment-related sequelae in colorectal cancer survivors are common and attention needs to be focused on identifying patients with unmet treatment needs and the development of evidence-based treatment algorithms.

Retrospective evaluation of the utility of two-stepsurgery for facial basal cell carcinoma and squamous cell carcinoma.

In older patients with facial basal cell carcinoma (BCC) or squamous cell carcinoma (SCC), surgery should be aimed to reduce treatment-related sequelae and burden with achieving local tumor care. Therefore, we adopted a two-step surgery (TSS) involving the application of a dermal regeneration template onto the skin defect after tumor resection and subsequent reconstruction by full-thickness skin grafting. We performed a detailed comparison of conventional one-step surgery (OSS) and TSS, including evaluation of local tumor curability, postoperative cosmetic and/or functional impairments, and patient burden. Forty-six patients who underwent TSS and 104 patients treated with OSS were retrospectively investigated. The cohort consisted of 77 men and 73 women (median age, 83 years). The BCC: SCC ratio was 56.7%: 43.3%. The tumor size and excision margin were significantly larger in the TSS group than in the OSS group (p = 0.03). The histopathological margin was positive after the first surgery in six cases, but was negative after additional resection in all cases, regardless of OSS or TSS. Local recurrence was not observed in this study. The frequency of postoperative sequelae (POS) in TSS was slightly lower than in OSS (17.4% vs. 27.9%, p = 0.16). A shorter average operation time per session was significantly associated with the location of the vertical defect [below adipose tissue vs. within adipose tissue, estimate: −0.28 (hour), p < 0.001] and surgical procedure [OSS vs. TSS, estimate: −0.13 (hour), p = 0.03] by multiple regression models. The ratio of general anesthesia was relatively lower in TSS than in OSS (9.8% vs. 17.3%, p = 0.12). Thus, TSS showed a good local curability and POS statistically equivalent to OSS, reducing the surgical burden, particularly shortening each operation time without any adverse events, despite the TSS group having significantly larger tumors than the OSS group. Since TSS is a simple procedure, it can be an outstanding option for facial BCC and SCC.

Biomarkers for risk-based treatment modifications for CNS germ cell tumors: Updates on biological underpinnings, clinical trials, and future directions.

CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland. Histopathologically, GCTs are broadly classified into germinomas and non-germinomatous GCTs (NGGCTs). In general, germinoma responds well to chemotherapy and radiation therapy, with a 10-year overall survival (OS) rate of approximately 90%. In contrast, NGGCTs have a less favorable prognosis, with a five-year OS of approximately 70%. Germinomas are typically treated with platinum-based chemotherapy and whole-ventricular radiation therapy, while mature teratomas can be surgically cured. Other NGGCTs require intensive chemotherapy with radiation therapy, including whole brain or craniospinal irradiation, depending on the dissemination status and protocols. Long-term treatment-related sequelae, including secondary neoplasms and cerebrovascular events, have been well recognized. These late effects have a tremendous impact in later life, especially since patients are mostly affected in childhood or young adults. Intending to minimize the treatment burden on patients, the identification of biomarkers for treatment stratification and evaluation of treatment response is of critical importance. Recently, tumor cell content in germinomas has been shown to be closely related to prognosis, suggesting that cases with low tumor cell content may be safely treated with a less intensive regimen. Among the copy number alterations, the 12p gain is the most prominent and has been shown to be a negative prognostic factor in NGGCTs. MicroRNA clusters (mir-371-373) were also revealed to be a hallmark of GCTs, demonstrating the potential for the application of liquid biopsy in the diagnosis and detection of recurrence. Recurrent mutations have been detected in the MAPK or PI3K pathways, most typically in KIT and MTOR and low genome-wide methylation has been demonstrated in germinoma; this most likely reflects the cell-of-origin primordial germ cells for this tumor type. These alterations can also be leveraged for liquid biopsies of cell-free DNA and may potentially be targeted for treatment in the future. Advancements in basic research will be translated into clinical practice and can directly impact patient management. Additional understanding of the biology and pathogenesis of GCTs will lead to the development of better-stratified clinical trials, ultimately resulting in improved treatment outcomes and a reduction in long-term treatment-related adverse effects.

EPEN-15. Radiotherapy with helium ions has the potential to improve both endocrine and neurocognitive outcome in pediatric patients with ependymoma

BACKGROUND: Ependymoma are the third most frequent pediatric brain tumors. To prevent local recurrence, the resection site should be irradiated. Especially the treatment of pediatric patients requires precise dose application and optimal protection of organs at risk. Compared to photon radiation treatment, proton therapy often achieves better results regarding target coverage and organ-sparing. Due to their physical properties, helium ions can further reduce side effects, providing better protection of healthy tissue despite similar target coverage. PATIENTS AND METHODS: In our in-silico study, 15 pediatric patients (median age six years) with ependymoma located in the posterior cranial fossa were considered. All patients underwent adjuvant radiotherapeutic treatment with active scanned protons at Heidelberg Ion-Beam Therapy Center (HIT). Both helium ion and highly conformal IMRT plans were calculated to evaluate the potential dosimetric (and clinical) benefit of ion beam therapy compared to the current state of the art photon-based treatments. RESULTS: Target coverage was comparable in all three modalities (He, H+, Ph): homogeneity indices (HI) and inhomogeneity coefficients (IC) of HIHe=5.8±3.8, HIH+=7.5±4.0, HIPh=6.4±4.3, ICHe=0.2±0.1, ICH+=0.2±0.1, ICPh=0.2±0.1. As expected, the integral dose absorbed by the healthy brain tissue could be reduced significantly using helium ions versus IMRT (-45.3%±15.1%). Based on our preliminary results, even compared to active scanned protons – currently the most precise radiation technique worldwide – the relative dose reduction for critical neuronal structures using helium ions on average amounts to -27.2%±14.4%. CONCLUSION: Previous studies could clearly demonstrate that the dosimetric advantage of protons translates into a measurable clinical benefit for pediatric patients with brain tumors. Given the dose response relationship of critical organs at risk, the results of our in-silico study provide a strong rationale that the use of helium ions has the potential to even further reduce the risk for treatment related sequelae.

MEDB-07. Long-term medical and functional outcomes of medulloblastoma survivors: a population-based, matched cohort study

BACKGROUND: Most medulloblastoma survivors suffer from late treatment-related sequelae. There are no population-based studies examining such late effects in a dedicated cohort of medulloblastoma survivors. METHODS: Using a provincial pediatric cancer registry, all 5+ year medulloblastoma survivors diagnosed between 1987-2015 in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (five years from latest of diagnosis, or relapse or subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse or new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, and receipt of homecare services between cohorts, accounting for matching and competing risks. RESULTS: We identified 230 cases [65.7% female; median diagnostic age: 7y, interquartile range (IQR) 4-10; median attained age: 24y, IQR 18-31] and 1150 controls. One hundred eighty-seven (81.3%) received craniospinal irradiation. Ten-year survival probability after index was 92.4% in cases and 99.4% in controls (HR 21.5, 95% CI 9.8-54.0). Cases were at higher risk for hospitalizations (HR 3.4, 95% CI 2.7-4.3), stroke (HR 45.6, 95% CI 12.8-289.8), hearing loss (HR 96.3, 95% CI 39.7-317.3), and requiring homecare services (HR 7.9, 95% CI 5.8-10.9). By 10 years after index, 4.8% (95% CI 2.2-9.0) of survivors had experienced a stroke compared to 0.1% (95% CI 0.01-0.7) of controls. CONCLUSIONS: Survivors of childhood medulloblastoma experienced an increased risk of mortality and serious morbidity compared to population controls. Consideration for mitigation strategies or early interventions in preventing neurovascular sequelae and hearing loss is warranted, as are dedicated supports for survivors.

Characterizing genitourinary exam disruptions in women presenting to a sexual health after cancer program.

e24048 Background: While treatment-related sexual health sequelae are documented using validated patient-reported outcome measures, the anatomic changes associated with cancer treatment are not well described, which may lead to an underestimation of the severity of these symptoms. To fill this knowledge gap and improve the management of these anatomic disruptions, we sought to objectively report the genitourinary findings of women presenting to a sexual health after cancer program over one year. Methods: At their first visit, patients undergo a thorough history and physical with a focus on the genitourinary exam. Patient demographics, primary symptoms, and treatment history were retrospectively collected and correlated to vaginal assessment scale (VAS) scores of female cancer patients presenting to the MUSIC (Menopause, Urogenital, Sexual Health and Intimacy Clinic) Program at an NCI-designated cancer center. Results: Between 2020-2021, 104 female cis-gender women with a median age of 46 (range 19-75) at diagnosis were seen. 56% identified as Hispanic/Latinx. Mean age was 47 (19-75), and most were treated for breast (80%) or gynecologic (10%) cancer. Primary complaints included vaginal dryness (53%), painful sex (45%), low desire (36%), hot flashes (22%), problems with orgasm (5%), urinary symptoms (10%), chronic pelvic pain (4%), or a need for complex contraceptive counseling (1%). Of those where a VAS was performed (n = 89), patients were found to have mild or moderate/severe loss of rugae (78%), loss of elasticity (84%), loss of vascularity (86%), and/or dryness (88%). Alarmingly, almost half were found to have some element of vaginal stenosis on exam, either vaginal scarring/adhesions (6%), foreshortened vagina (13%), or a narrowed introitus (47%) (Table). Conclusions: In an initial consult of women seeking care for sexual health after cancer treatment, the most common concerns were vaginal dryness, painful sex, and low desire. Despite only approximately half reporting either dryness or painful sex, most were found to have genitourinary disruptions in anatomy at presentation, including vaginal stenosis. The presence of vaginal stenosis in sexual health survivors who did not undergo pelvic radiation deserves future study as these findings often present as a complete inability to have penetrative intercourse.[Table: see text]

Survivorship profile and post-treatment quality of life of oral cancer survivors in comparison with caregivers: An analysis of a real-world cohort of a developing country.

e18036 Background: Oral cavity cancer is the second most common cancer in India; India bears the most burden of oral cancer in the world. The most effective way to study the effectiveness of treatments is in clinical trials, but the quality of life (QOL) and post-treatment effects of those treatments are seldom studied in real-world settings. Methods: All oral cancer survivors treated with curative intent at our institute from September 2019 to January 2021, who were disease-free for a minimum of six months following treatment, were included in this study. The QOL of these cancer survivors was compared with that of their caregivers using the WHOQOL BREF questionnaire. The complete survivorship profile was evaluated using a Constant shoulder score for shoulder dysfunction, clinical oral dryness score (CODS) for xerostomia, Sydney Swallow Questionnaire (SSQ) for swallowing dysfunction, Patterson scale for lymphedema, Comprehensive Score for financial Toxicity (COST)‐Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire for financial toxicity, Depression, Anxiety and Stress Scale - 21 Items (DASS-21) for psychological wellbeing. Results: A total of seventy-nine survivors were included. The median age was 49 years. Though both survivors and caregivers had similar QOL scores in the physical and environmental domains, survivors had poor scores in the social (M = 58.7,SD = 21.9) and psychological domains (M = 60.4,SD = 15.6). The T stage (p = 0.06), surgery (p = 0.008), and trismus (p = 0.03) were significant factors affecting swallowing. Those patients who had undergone selective neck dissection had better shoulder scores compared to those who had modified radical neck dissection (p = 0.006). 75% of people had xerostomia and 10.9% had severe xerostomia. Internal lymphedema was seen in 30.4% of people. Depression and anxiety were recorded in 46 (58.2%) and 33 (41.8%) patients respectively. Employment status (p = 0.04) and treatment modality (p = 0.05) were significant factors affecting financial toxicity. Conclusions: Oral cancer survivors had a poor psychosocial QOL compared to their caregivers. Treatment-related functional sequelae had a significant negative impact on quality of life across all domains. Clinical trial information: CTRI/2020/07/026848.

Long-term medical and functional outcomes of medulloblastoma survivors: A population-based, matched cohort study.

10053 Background: Most medulloblastoma survivors suffer from late treatment-related sequelae. There are no population-based studies examining such late effects in a dedicated cohort of medulloblastoma survivors. Methods: Using a provincial pediatric cancer registry, all 5+ year medulloblastoma survivors diagnosed between 1987-2015 at &lt;18 years of age in Ontario, Canada were identified and matched to cancer-free population controls based on age, sex, and geographical location. Cases were followed from the index date (five years from latest of diagnosis, or relapse/subsequent malignancy prior to age 18 years) until December 31, 2020 or censorship (death, or relapse/new cancer after age 18 years). Clinical data were linked to administrative health databases to estimate the cumulative incidences and cause-specific hazard ratios (HR) of mortality, hospitalizations, strokes, hearing loss requiring a hearing aid, and receipt of homecare services between cohorts, accounting for matching and competing risks. We evaluated demographic, disease, and treatment predictors of mortality using Cox proportional hazards models. Results: Of 389 medulloblastoma diagnoses in the study period, 159 (40.9%) were excluded, most commonly due to early death prior to the index date. Two hundred thirty cases were matched to 1150 controls (Table). Ten-year survival probability after index was 92.4% in cases and 99.4% in controls (HR 21.5, 95% CI 9.8-54.0). Cases were at higher risk for hospitalizations (HR 3.4, 95% CI 2.7-4.3), stroke (HR 45.6, 95% CI 12.8-289.8), hearing loss (HR 96.3, 95% CI 39.7-317.3), and requiring homecare services (HR 7.9, 95% CI 5.8-10.9). By 10 years after index, 4.8% (95% CI 2.2-9.0) of survivors had experienced a stroke compared to 0.1% (95% CI 0.01-0.7) of controls. None of the candidate predictors were significantly associated with mortality on univariate analyses. Conclusions: Survivors of childhood medulloblastoma experienced an increased risk of mortality and serious morbidity compared to population controls. Consideration for mitigation strategies or early interventions for preventing neurovascular sequelae and hearing loss is warranted, as is dedicated supports for survivors. [Table: see text]