Cancer-directed Therapy Research Articles

Non-AIDS defining cancers in HIV-infected individuals: a concise review

Non-acquired immunodeficiency syndrome (AIDS)-defining cancers (NADCs) present a growing concern in human immunodeficiency virus (HIV)-infected individuals, impacting morbidity and mortality rates. This paper synthesizes current epidemiological data and explores the multifaceted relationship between HIV infection and NADC risk. Epidemiological studies indicate a shifting landscape of cancer incidence among HIV-infected populations, with a notable rise in NADCs over recent decades. Factors such as prolonged life expectancy due to effective antiretroviral therapy (ART) and aging of the HIV-infected population contribute to this trend. Despite the overall decline in AIDS-defining cancers, NADCs have emerged as a significant cause of morbidity and mortality in HIV-infected individuals. Immunodeficiency, chronic inflammation, and oncogenic viral co-infections, such as human papillomavirus and hepatitis C virus, compound the risk of developing NADCs. Diagnostic challenges persist, with delayed detection and suboptimal management contributing to poor outcomes. Treatment modalities for NADCs in HIV-infected individuals require careful consideration, balancing cancer-directed therapy with potential interactions with ART and immune reconstitution. Prevention strategies, including cancer screening and lifestyle modifications, are crucial in mitigating the burden of NADCs in this population. As the landscape of HIV care continues to evolve, understanding the epidemiology and clinical characteristics of NADCs is imperative for optimizing clinical management and improving outcomes in HIV-infected individuals.

Prevalence, treatment patterns, and survival of patients with brain metastases from small cell lung cancer: A retrospective study using the TriNetX Oncology Database

Abstract Background Brain metastases (BM) portend increased morbidity and mortality in patients with small cell lung cancer (SCLC). We aimed to characterize the prevalence, timing, treatment patterns, and survival outcomes of BM associated with SCLC over the past decade. Methods Data from 4014 patients with histologically confirmed SCLC were extracted from the TriNetX Oncology database. Clinical and demographic variables were compared between patients with and without BM using Chi-squared and t-tests. Kaplan–Meier and Cox regression analyses were used to evaluate overall survival (OS), after propensity score matching cohorts for age at diagnosis, sex, cancer stage at diagnosis, extracranial metastases, and cancer-directed therapy. Results Among 4014 patients with SCLC, 35.0% had BM (9.9% synchronous, 21.2% metachronous, 3.9% precocious). Patients who developed BM were younger (P < .001) at SCLC diagnosis, more likely Black/African American (P = .0068), and presented with more advanced cancer stages (P < .001) than patients who did not develop BM. The median BM-free survival from the time of SCLC diagnosis was 27.9 months. Patients with BM received higher rates of cancer-directed therapies than those without BM. Synchronous BM was associated with lower OS than metachronous BM after the diagnosis of SCLC (HR[95% CI] = 1.56[1.32–1.83]), but there was no difference in OS after the BM diagnosis. OS did not differ between patients with BM and patients with extracranial metastases only, following the diagnosis of metastatic disease. Conclusions Our findings support that independently of the chronicity of BM diagnosis, patients with SCLC have poor survival once the diagnosis of BM is conferred.

Adherence to pretreatment hepatitis B virus (HBV) screening in patients with cancer after implementation of built-in order set.

330 Background: Patients with a history of HBV exposure are at risk of reactivation when receiving treatments that affect the immune system, such as cancer-directed therapies. ASCO guidelines recommend universal HBV screening prior to initiation of cancer-directed therapies to prevent hepatic dysfunction and delays in cancer care. However, significant variation remains in clinical practice. Improving HBV screening is of special interest at our institution, given that we serve a large proportion of Asian immigrants at high risk of prior HBV exposure. With our institution’s transition to EPIC on Apr 1, 2022, the HBV serology order set was incorporated into the pre-treatment checklist of every cancer therapy plan. We studied the rates of HBV screening before and after implementing this change. Methods: We identified patients with cancer starting systemic cancer treatment at our institution between Oct 1, 2021 – Mar 31, 2022 (pre-EPIC period), and Oct 1, 2023 – Mar 31, 2023 (post-EPIC period). Patients who received only endocrine therapy, transferred care, or lost to follow-up prior to treatment initiation were excluded. To select a random sample from each time-period of interest, patients were assigned a random number, sorted based on this random number, and then reviewed in order. All data was collected retrospectively by manual chart review. Results: We randomly selected and reviewed 69 patients from pre-EPIC period, and 75 from post-EPIC period. Their demographic, disease, and treatment characteristics are summarized in the table. HBV screening rates were 42% and 80% in the pre-and post-EPIC periods, respectively (p<0.001). Twenty-one (14.6%) patients screened positive for HBV core antibody, among whom six (5.1%) had negative surface antibodies. Conclusions: The built-in HBV serology order set significantly improved rates of hepatitis B screening prior to starting systemic cancer-directed treatment. It is a low-cost and highly effective intervention. Our next steps are to determine how a higher adherence to HBV screening guidelines impacted the management of patients with prior HBV exposure. Pre-EPIC:Oct 1, 2021 - Mar 31, 2022 (N=69) Post-EPIC: Oct 1, 2022 – Mar 31, 2023 (N=75) P values Age at diagnosis (years), mean (SD) 62.1 (1.4) 65.2 (1.6) 0.15 Female (%) 40 (58.0) 35 (46.7) 0.18 Race (%): 0.051 White 51 (73.9) 49 (65.3) Asian 8 (11.6) 20 (26.7) Other 10 (14.5) 6 (8.0) Cancer type (%): 0.39 Hematological Malignancies 19 (27.5) 16 (21.3) Solid Tumor 50 (72.7) 59 (78.7) Metastatic Disease (%) 24 (34.8) 25 (33.3) 0.95 Treatment Type (%): 0.13 CD20 mAb+/- other 3 (4.4) 9 (12.0) Chemotherapy+/-other 52 (75.4) 57 (76.0) Other 14 (20.3) 9 (12.0) mAb: monoclonal antibody.

Abstract C071: Comprehensive genomics-informed prospective older adult (OA) cancer registry: Initial findings from gastrointestinal (GI) malignancy

Abstract The REACH study (Resilience and Equity in Aging, Cancer, and Health) assesses the impact of geriatric consultation on reducing emergency department and/or unplanned hospitalization visits (EDH) for OA age 70+ diagnosed with GI cancer. We sought to develop an OA GI cancer registry (REACH Registry) within the REACH intervention integrating 1) disease and treatment factors from the PRISSMM cancer taxonomy model with 2) patient reported outcomes and 3) geriatric assessment (GA) measures predictive of function, toxicity, and survival. We reviewed GA measures using the modified Rockwood frailty scale, PROMIS-10 global mental and physical scores, Karnofsky performance status, health-related social needs, and disease/treatment factors using PRISSMM cancer taxonomy for OA consented to REACH in the GI Cancer Center at Dana-Farber Cancer Institute (DFCI) from January 2022–April 2024. OA were eligible if age 70+ at initial DFCI consult visit and diagnosed with any GI cancer. The GA stratifies OA by frailty level on a 0-1 scale: Fit/Robust (score range 0–0.19), Pre-Frail (0.2–0.34), and Frail (0.35–1.0). PRISSMM is a cancer data modeling system developed for the American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative; it includes pathology, radiology/imaging, symptoms, and molecular markers curated by trained research staff from unstructured EHR data. From Jan. 2022–Apr. 2024, 50 OA consented to REACH registry (94 eligible). Of those, 44% (n=22) have PRISSMM data available for analysis. Most OA reported white race (90%, n=45) and female gender (52%, n=26). Pancreatic cancer was the most common diagnosis (n=21), followed by colon (9), biliary (5), and esophageal (4). Most OA completed GA (90%, n=45) with 51% screened Fit/Robust (n=23), 47% Pre-Frail (n=21), and 2% Frail (n=1). Type 2 diabetes mellitus was the most commonly reported comorbid condition (26%, n=13), followed by chronic kidney disease (n=6) and congestive heart failure (n=3). Of the 22 OA with available PRISSMM data, 59% (n=13) were diagnosed with stage IV disease and 100% received cancer-directed therapy; 72% (n=16) received standard care, 27% clinical trial (n=6). Most OA consented for tumor somatic genomic testing (77%, n=17). At the time of data curation 24 months from assessment, 20 patients had died, 30 were alive. Evaluation of the REACH intervention geriatric consultation on EDH outcome is forthcoming. REACH registry is the first GI cancer database inclusive of geriatric specific measures alongside curated disease, treatment and genomic data. We observed a higher rate of genomic testing and treatment initiation than reported in the literature. We anticipate that by September 2024, a larger cohort of REACH Registry participants will have completed PRISSMM data available for analysis. Future study will compare EDH for REACH vs. non-REACH OA as well as treatment patterns of this OA cohort evaluated at a large comprehensive cancer center and associated community sites. Citation Format: Tammy T. Hshieh, Rachel L. Weitzner, Siri Rosenberg, Leila Rostamnjad, Lauren K. Brais, Nora Horick, Tamryn Gray, Jiping Wang, Jeffrey Meyerhardt, Nadine J. McCleary. Comprehensive genomics-informed prospective older adult (OA) cancer registry: Initial findings from gastrointestinal (GI) malignancy [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C071.

COVID-19 Disease in Children With ALL Receiving Maintenance Therapy: Do Not Discount the Risk.

Unlike most childhood cancers, therapy for ALL includes a prolonged maintenance phase during which children typically resume regular activities. Physicians need data regarding the persistent impact of COVID-19 in this population to help guide families after the pandemic. The Pediatric Oncology COVID-19 Case Report (POCC) collects deidentified data (sociodemographics, clinical data [cancer, COVID-19 course]) on children, adolescents, and young adults with cancer and COVID-19 from 104 US pediatric oncology institutions. The analysis presented here compares children (≤21 years) with ALL in maintenance (ALL-MTN) with all other children with cancer and COVID-19. Multivariable analyses adjust for age, race/ethnicity, insurance, absolute neutrophil count at the time of infection, vaccination, and comorbidities. Compared with other children reported to POCC (n = 1,190), those in ALL-MTN (n = 481) were less often hospitalized (23% v 29%, P = .01) or admitted to the intensive care unit (ICU: 3% v 5%, P = .01); these findings persisted in multivariable analysis (hospitalization: odds ratio [OR], 0.7 [95% CI, 0.6 to 0.9]; ICU: OR, 0.5 [95% CI, 0.2 to 0.8]). However, cancer-directed therapy was changed more often for children in ALL-MTN (50% v 33%, P ≤ .01; OR, 2.0 [95% CI, 1.6 to 2.5[). Vaccination was an independent prognostic factor in our multivariable model, decreasing odds of hospitalization (OR, 0.7 [95% CI, 0.5 to 0.9]). Children in ALL-MTN required fewer hospitalizations and ICU admissions but more therapy modifications than other children with cancer. Vaccination against COVID-19 reduced the odds of hospitalization.

Glucospanlastics: innovative antioxidant and anticancer ascorbyl-2-glucoside vesicles for striking topical performance of repurposed itraconazole.

Presently, the development of functional derivatives exploiting biocompatible pharmaceutical materials has become a pressing demand. Among them, ascorbyl-2-glucoside (AA-2G), an ascorbic acid derivative, has significant potential owing to its stability, solubilization and antioxidant prospects. Herein, AA-2G was utilized for the fabrication of itraconazole (ITZ) spanlastics, which were denoted as "glucospanlastics". Subsequently, the newly designed glucospanlastics were characterized to determine their dimensions, charge, entrapment, solubilization efficiency, morphology, stability and antioxidant activity. Further, their cytotoxicity towards A431 cells and their ex vivo skin deposition were investigated. Subsequently, the competence of the formulated cream containing glucospanlastics to suppress Ehrlich carcinoma and modulate the antioxidant profile was evaluated in vivo. The results revealed that the proposed nano-sized glucospanlastics performed better than conventional spanlastics (without AA-2G) with respect to optimal solubilization efficiency and ITZ entrapment (>95%) together with antioxidant, cytotoxic and skin permeation potentials. More importantly, glucospanlastics containing 10 and 20 mg AA-2G demonstrated considerable tumor suppression and necrosis, improvement in glutathione (GSH) content by 1.68- and 2.26-fold, elevation of total antioxidant capacity (TAC) levels by 1.67- and 2.84-fold and 1.78- and 2.03-fold reduction in malondialdehyde (MDA) levels, respectively, compared to a conventional ITZ cream. These innovative antioxidant vesicles show future potential for the dermal delivery of cancer-directed therapies.

Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214

BackgroundImmunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of...

The spectrum of late radiation sequelae in head and neck cancer

ABSTRACT Introduction: Concurrent Chemoradiation is the standard of care in the treatment of unresectable locally advanced head and neck cancer. Some of the acute side effects seen after or alongside the head and neck radiotherapy include dermatitis, mucositis, xerostomia, dysphagia and swallowing dysfunction. Evolving data demonstrate that acute toxicities may persist long-term and develop into late effects. In addition, late effects may manifest months or years after completion of therapy, persisting for years or even lifelong, far longer than previously believed. When severe, late effects may profoundly affect function and quality of life. The present study was conducted to analyze the spectrum of late radiation toxicities in head and neck cancer patients treated with radical external beam radiation therapy and to determine its prevalence and severity. Materials and Methods: This prospective observational study was conducted in the Department of Radiotherapy, Christian Medical College and Hospital, Ludhiana. In all patients with a histopathological diagnosis of head and neck carcinoma who have received radical radiation therapy alone or definitive chemoradiation as part of cancer-directed therapy. Results: Salivary gland toxicity was the most common toxicity encountered in head and neck cancer survivors resulting in dysphagia followed by dental caries, subcutaneous late effects and dysphagia. As expected, the spectrum of side effects correlated with the primary site, stage of disease and ECOG performance status. Conclusion: Technological advancement in radiation planning and equipment has resulted in a reduction in the most feared side effects of radiation which has led to improvement in the quality of life of the survivors. As no technology can entirely protect normal tissues from irradiation, utmost care should be taken to minimize the radiation dose received by normal tissues by following preventive and supportive measures.

Randomized double-blind placebo-controlled trial evaluating pregabalin for chronic cough in patients with lung cancer.

LBA12082 Background: Chronic cough is a distressing symptom that detracts from the quality of life (QoL) of patients with cancer. Developing effective therapies for cough is an unmet need, with no approved medicines available. Neuromodulators like pregabalin may act centrally as cough suppressants. Methods: Randomized double-blind placebo-controlled study in the Department of Medical Oncology at Tata Memorial Hospital (Mumbai, India) in patients with locally advanced/metastatic non-small-cell lung cancer (NSCLC) with at least 2 weeks history of moderate or severe cough. Patients had ECOG PS 0-2, and creatinine clearance > 60 mL/min. Randomization was 1:1 to pregabalin 300 mg orally daily or matching placebo, both administered for 9 weeks. Primary endpoint was the difference in cough severity as measured by Visual Analog Scale (VAS) after 9 weeks treatment with pregabalin versus placebo. Secondary endpoints included cough severity on day 7 and week 9 measured by VAS, and Manchester Cough in Lung Cancer Scale (MCLCS); side-effects, and QoL assessed by EORTC QLQ C30 and LC13. Means of the change from baseline scores were calculated for patients in each arm, and compared between two arms by independent samples Mann Whitney U test. P < 0.05 was considered significant. Results: Between Jul 2022 and Dec 2023, we enrolled 166 patients: 83 to each arm. Median age was 56 years (IQR, 47-62.5); 112 (67.5%) were male, and 149 (89.8%) had metastatic NSCLC. Baseline cough severity was grade 2 in 127 (76.5%) and grade 3 in 37 (22.6%); median cough duration was 163 days. The therapy (pregabalin/placebo) was well tolerated in both arms, with no difference in grade > 3 toxicities between the two arms; P=0.908. Systemic cancer-directed therapy was started in 95.2% and 91.4% of patients in the pregabalin and placebo arms, respectively; P=0.328. By week 9, subjective improvement in cough was reported by 45 (57%) patients in pregabalin arm, and 40 (52.6%) patients in placebo arm; P=0.846. The mean VAS score (in mm) decreased from 71.58 at baseline, to 45.32 at day 7, and 19.73 by week 9 in the pregabalin arm; corresponding values in the placebo arm were 71.74, 46.23, and 21.18, respectively; P=0.530. Cough assessment by mean MCLCS scores showed a similar decrease throughout the course of the study, with no statistically significant differences between the two arms (Pregabalin-Baseline: 27.63, Day 7: 23.49, Week 9: 17.39; Placebo-Baseline: 27.28, Day 7: 23, Week 9: 17.34); P=0.455. There was no significant difference in QoL between the two arms. Mean LCCO (cough symptom question on QLQ LC13) score decreased from 75.9 (baseline) to 54.2 (day 7) to 36.4 (week 9) in pregabalin arm, vs 66.3, 54, and 31.4, respectively, in placebo arm; P=0.150. Conclusions: Pregabalin does not lead to a significant decrease in cough in patients with lung cancer. Systemic cancer-directed therapy is the most effective antitussive therapy for cancer-induced cough. Clinical trial information: CTRI/2020/11/029275 .

Inpatient outcomes of patients with new solid tumors admitted to a comprehensive cancer center.

e23056 Background: Hospitalized cancer patients demonstrate multiple challenges including management of acute illnesses, establishment of the cancer diagnosis, creation of a goal concordant care plan, and post-hospital disposition. Yet, there has been limited research regarding characteristics and outcomes of new to hospital oncology patients. Methods: We performed a retrospective chart review of patients with suspicion or confirmed solid tumor cancer diagnosis who were admitted without an established MD Anderson Cancer Center oncologist. We assessed length of stay, ICU utilization, 30-day readmission rate, inpatient mortality, and discharge disposition. We compared the results to our group’s established oncology patients. Statistical analysis was performed using Chi-squared testing. Results: Between November 2022 and January 2023, 201 unique new patients were reviewed out of 1635 admissions. Of those 103 (51.2%) were males, median age of 60 (range: 22-79), White including Hispanics 118 (59%), African Americans 46 (23%), others 33 (18%). Of the study population, 88 (43.8%) did not have a confirmed cancer diagnosis, of which we established a cancer diagnosis in 68 (77.3%) and ruled out cancer in 8 (4%). Of the 113 (56.2%) diagnosed at outside facilities, 63 (55.8%) were treatment naive and 22 (19.4%) had their cancer diagnosis revised. Of 175 patients which had staging information, 150 (85.7%) were stage 4. During the index admission, 45 (22.4%) patients had cancer-directed therapy. The average and geometric mean length of stay (days) for new patients was 12.1 and 8.8, respectively, compared to the established group of 8.2 and 6.1 (p < 0.001). Inpatient mortality was higher in new patients (10.5% vs 6.8%, p < 0.001) and they were more likely to be referred to hospice services (17.4% vs 8.3%, p < 0.001). Furthermore, hospice referral was higher in the unestablished, previously treated group compared to treatment naive patients (28% vs 13.9%, p = 0.003), however inpatient mortality was similar (12% vs 9.9%, p = 0.63). ICU stay, 30-day readmission rate, discharge to home vs placement were similar in new and established patients (Table 1). Conclusions: Admitted new oncology patients typically present with advanced disease and had longer length of stay, mortality rates, and hospice referrals compared to established patients. Further research is needed to identify and improve care barriers to new inpatients, focusing on improving workflow process and timely goal concordant care discussions. [Table: see text]

PLWH and lung cancer: A single cancer center experience in Philadelphia, PA.

e20502 Background: Lung cancer has been identified as the leading cause of cancer-related deaths in people living with HIV (PLWH), and disproportionately affects this population independently of smoking status and CD4 count. At the Sidney Kimmel Cancer Center (SKCC) at Jefferson Health, we serve a uniquely underserved patient population of PLWH. As PLWH were categorically excluded from most lung cancer clinical trials, we aim to study the clinical course of our patients with HIV and lung cancer. Methods: A retrospective review of 36 patients within SKCC at Jefferson Health in Philadelphia, PA from 2016 to 2023 were obtained utilizing ICD codes for lung cancer and HIV. Patients who were found to have HIV after their lung cancer diagnosis were excluded. Patient demographics, viral status, antiviral therapy, lung cancer stage, histology, molecular and fusion status, PD-L1 status, form of cancer-directed therapy, date of progression, last date of treatment, and date of death were recorded. Results: Of our 36 patients, 24 (66.7%) were male, and 20 (55.6%) racially identified as Black. 27 patients had NSCLC (20 with adenocarcinoma, 7 with squamous cell carcinoma), and 3 had SCLC. 24 (66.7%) patients had an undetectable viral load at the time of diagnosis and 35 (97.2%) were on antiviral therapy. 32 of 36 patients (88.9%) had advanced stage at the time of diagnosis; 11 had stage III disease (30.6%), and 21 (58.3%) had stage IV disease. Only 4 patients (11.1%) were diagnosed with stage I disease. The mean age of patients at diagnosis was 61.6 years (+/- 8.7 years). Of 18 patients with molecular testing performed, 4 had a KRAS mutation (22.2%) and 1 (5.6%) had a targetable EGFR mutation. Of 16 patients with PD-L1 testing, 7 (43.8%) had 0% expression, 8 (50%) had 1-49% expression, and 1 patient (6.2%) had PD-L1 expression > 50%. The OS among this cohort was 1.3 years (95% CI: 0.8-3.8 years). Conclusions: Our cohort of patients demonstrated more advanced disease at presentation, a younger mean age at diagnosis and poor OS. These trends exist despite the majority of these patients having an undetectable HIV viral load at the time of diagnosis in the setting of ongoing antiviral therapy, indicating a potential relationship between even well-controlled HIV and aggressive lung cancer that warrants further exploration.

End of life treatment in gynecological cancers in an integrated care model: A single institution experience from Oman.

e24036 Background: The use of chemotherapy closer to the end of life (EOL) and the optimal time of initiating palliative care interventions are subjects of ongoing debate. In a traditional care model (TCM), the institution of EOL care is a complex decision-making process, that involves patient, family members, and the oncologist, and involves transfer of patients from one to the other service. Integrated care model (ICM) is a newer concept, is designed around the needs of the patients, and may have the potential to improve quality of life and reduce the cost of healthcare towards EOL. At our center, we work in ICM in organ-based clinical programs and report the use of systemic treatment in patients with gynecological cancers (GC) nearing EOL. Methods: We analyzed retrospectively the use of chemotherapy and other systemic cancer-directed therapies in patients with GC, who died between Sept 2021 and December 2023 at a single institution. Information on the cancer-type, intention of treatment, and the time between last treatment and death was obtained from electronic patient records (EPR). Results: Over the study period, a total of 22 patients passed away. All patients received palliative care as part of the integrated care. All patients had been declared ‘not for resuscitation’ before death. Twelve patients had ovarian cancer, 5 had endometrial cancer, 4 had cancer of cervix, and one had vulvar cancer. The median age at diagnosis was 53 years (29-80). The systemic treatment was 1st line in 5 patients (23%), 2nd line in 8 patients (36%), and 3rd or more line in 6 patients (27%) respectively. Three patients (14%) did not receive any cancer-directed treatment (aged 80, 71 and 61). The ultimate line of treatment was cytotoxic chemotherapy for all patients, except for one who received Olaparib, and one who received trastuzumab with chemotherapy. There was no treatment-related mortality. The median time from last treatment to death was 55 days. Of the 19 patients who received treatment, 6 patients (32%) received treatment in the last 30 days, 5 between 30 and 60 days (26%), 5 between 60 and 90 days (26%), and 3 more than 90 days before death. Four patients died at home. Age at diagnosis (51 vs 55 years), age at death (51.5 vs 57.5 years), or time from diagnosis to death (11.5 vs 22 months), did not predict whether patients received treatment within the 30 days of death or earlier. Conclusions: All patients received palliative care as part of integrated cancer care. The ICM may have led to lower use of cancer treatment near EOL. The data may provide a benchmark for the region.

Survival analysis and associated factors in metastatic early-onset colorectal cancer vs. metastatic average-onset colorectal cancer.

e15549 Background: Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before age 50 and its incidence has been increasing during the last decade. Average-onset colorectal cancer (AO-CRC) has presented a steady decline in incidence and related mortality over the past 20 years. There is controversy surrounding the disparities in outcomes and overall survival (OS) in EO-CRC vs. AO-CRC. Our study compared the OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified associated factors. Methods: Data on patient characteristics, tumor characteristics, incidence and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 with confirmed diagnosis of all histologic subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site code C180, C182-9, C209 and histology codes: 8000, 8010, 8012, 8013, 8020-2, 8031-33, 8041, 8045, 8070-2, 8083, 8123-4, 8140, 8144-45, 8201, 8210-11, 8213, 8220-1, 8240, 8243-46, 8249, 8253, 8255, 8260-3, 8261-3, 8265, 8310, 8323, 8480-1, 8490, 8507, 8510, 8550, 8560, 8570, 8574, 8936, 8980. OS distributions and CCS were conducted using the Kaplan-Meier method and log-rank test was used to assess differences between mEO-CRC and mAO-CRC. Cox regression model used to assess associations between variables. Results: mEO-CRC constituted 17.79% of the cases, while 82.21% were mAO-CRC. Most patients with mEO-CRC were between 45-49 years old (47.66%), males (52.16%), white (72.57%), with histology of adenocarcinoma (87.30%). Left colon tumors were most prevalent in both groups (40.26%), but higher among mEO-CRC than in mAO-CRC (49.63% vs 38.23%, p < 0.001). mEO-CRC were more likely to receive chemotherapy (87.23% vs. 66.66%, p < 0.001) and radiotherapy (14.92% vs. 9.51%, p < 0.001), while surgery was similar in both groups (87.71% vs. 88.52%, p = 0.140). Patients with mEO-CRC had a higher OS (HR: 1.53, CI 95% 1.47-1.59, p < 0.001), as well as a higher CSS (HR: 1.33, 95% CI: 1.27-1.39, p < 0.001) when compared to mAO-CRC. mEO-CRC also had a significantly better median overall survival (30 months vs. 18 months p < 0.001). Factors associated with worse OS include mAO-CRC (p < 0.001), mucinous adenocarcinoma (p < 0.001), male sex (p 0.003) and no surgical intervention (p < 0.001). Conclusions: Patients with mEO-CRC had better OS and CSS when compared to patients with mAO-CRC and were more likely to receive cancer-directed therapy which could be explained by the mEO-CRC cohort having a higher performance status, less comorbidities, and better tolerance to cancer-related therapy. Factors associated with worse OS and CSS are mAO-CRC, mucinous adenocarcinoma, male sex and lack of surgical intervention. Furthermore, it is crucial to continue studying potential candidates who would benefit from early CRC screening.

Treatment rates and reasons for non-treatment in a real-world cohort of patients with pancreatic cancer.

e13554 Background: The proportion of patients who receive treatment for pancreatic ductal adenocarcinoma (PDAC) and reasons for non-treatment in real-world patient populations are poorly understood. Our study aims to determine treatment rates, predictors for non-treatment, and the rationale for declining treatment in a well-defined, diverse, community-based patient population. Methods: We identified all adult patients with PDAC (n = 3852) between 2010 and 2020 through the Kaiser Permanente Northern California Cancer Registry. Patients were stratified by age and tumor characteristics to determine rates of oncologic therapy. Multivariable logistic regression was used to assess how covariates were associated with receiving treatment. A detailed chart review of all patients ≤ 65 years and a random sample of 100 patients > 65 years with non-metastatic disease who did not receive treatment was performed to better understand the reasons for non-treatment. A random sample of 20 patients with metastatic disease who did not receive treatment were also reviewed. Results: Of patients with PDAC, 77.7% of patients with non-metastatic and 56.2% with metastatic disease received any cancer-directed treatment. A multivariate analysis showed no statistically significant differences by race/ethnicity or gender. Increasing age was a significant negative predictor of treatment. Charlson comorbidity index (CCI) did not influence treatment rates in patients with non-metastatic PDAC, but in patients with metastatic disease those with CCI 3+ had a decreased odds of receiving treatment. Of patients ≤ 65 years with non-metastatic disease, 90.3% were seen by an oncologist, and of those patients 89.3% were offered treatment. The primary reason for declining treatment was patient/family preference in 80.8%, followed by PDAC-related frailty in 11.5%, and medical comorbidity/other malignancy in 7.69%. Similarly, of patients > 65 years with non-metastatic disease, the majority were also seen by an oncologist, offered treatment, and declined due to personal preference. The same trends were noted in patients with metastatic PDAC. Conclusions: A significant proportion of patients with PDAC did not receive cancer-directed treatment in a real-world, community-based patient population, and this was more likely for patients with metastatic disease. Race and gender did not influence whether patients received treatment in this fully insured patient population and comorbidity had a small effect. Patients of increasing age, however, were less likely to receive treatment. Most patients who did not initiate treatment did so primarily due to patient/family preference despite being offered cancer-directed therapy by their treatment team. These findings may help guide the development and utilization of patient decision-aids in PDAC to improve goal concordant care that accounts for patients’ preferences and values.

Effect of the timing of recurrence on survival among patients with breast cancer with brain metastasis.

e14005 Background: Patients with Metastatic Breast Cancer (MBC) and brain metastasis (BM) have poor prognosis. There is a lack of data on the effects of timing of MBC diagnosis [de novo (d) vs recurred (r) MBC] and BM diagnosis [dBM vs later onset (lo) BM] on overall survival (OS). We conducted a natural history-type study to investigate these effects among MBC BM patients. Methods: The data for this retrospective single institute study was extracted from a database of MBC BM patients diagnosed with BM from Jan 2010 to June 2021. Definitions: dMBC= MBC at initial diagnosis (Dx); rMBC= MBC with prior history of early stage BC; dBM= BM diagnosed< 6 weeks (wk) from MBC Dx; loBM= BM diagnosed ≥ 6 wk from MBC Dx. The following endpoints were compared between dMBC vs rMBC: 1. interval from MBC to BM Dx (Interval MBC-BM) 2. OS from MBC Dx 3. OS from BM Dx. OS from BM Dx was compared between dBM vs loBM. Median endpoints were estimated using the Kaplan-Meier method and reported with 95% confidence intervals (CI). Cohorts were compared using the Logrank test and adjusted for other variables using Cox models. Results: Interval MBC-BM, OS from MBC Dx, and BM Dx were not statistically different between dMBC and rMBC groups in unadjusted analyses (See Table) and when adjusted in multivariate analyses. Median OS from BM Dx was significantly longer in dBM group vs loBM group (See Table). In multivariate model adjusting for variables at BM Dx (age, race, performance status, visceral disease, number of BM >1cm, leptomeningeal disease, BC receptor types), risk of death was higher in loBM group vs dBM group (Hazard Ratio, HR = 0.499; p=0.006). In dMBC group, 28.1% had dBM compared to 45.6% in the rMBC (p=0.083, Chi-square test). Subset analyses: Among rMBC group, median OS from BM Dx with dBM (n=42, OS=44.3 months (m), 95% CI 19.0-Not evaluable (NE)) was significantly longer compared to loBM (n=50, OS=13.7m (6.6-21.4)), p=0.002 (LogRank Test); but among dMBC group, there was no significant difference in OS from BM Dx with dBM (n=9, OS=32.4m (12.9-122.5)) vs. with loBM (n=23, OS= 17.8m (6.6-NE)), p=0.885. Conclusions: In a retrospective database of patients with BM from BC, time from MBC to BM diagnosis, OS from MBC diagnosis, and OS from BM diagnosis did not differ between those with recurrent vs de novo MBC. Interestingly, in unadjusted and adjusted analyses, OS from BM diagnosis was longer for those with de novo BM diagnosed at/around MBC diagnosis than those whose BM was later in onset. Earlier-onset BM in the MBC disease course could be more sensitive to cancer-directed therapies. Studies are needed to test this hypothesis.[Table: see text]

COVID-19 infection in children, adolescents, and young adults with Down syndrome and hematologic malignancies.

Children, adolescents, and young adults (CAYAs) with Down syndrome (DS) and hematologic malignancies are particularly vulnerable to infections and related complications. There are limited data regarding COVID-19 infections in this group. We aimed to understand the clinical course of COVID-19 in this population. This observational study leverages the de-identified clinical and sociodemographic data captured by the Pediatric Oncology COVID-19 Case Report Registry (POCC) regarding CAYAs with cancer and COVID-19. We evaluated CAYAs (≤21years at COVID-19 infection) with hematologic malignancies and COVID-19 reported from April 1, 2020 to May 2, 2023, comparing those with and without DS. Using multivariable logistic regression, we examined rates of hospitalization, intensive care unit (ICU) admission, respiratory support, and changes in cancer-directed therapy. Among 1408 CAYAs with hematologic malignancies, 55 had DS (CAYA-DS). CAYA-DS had higher rates of hospitalization, ICU admission, and respiratory support (p<.001) than CAYAs without DS. Similarly, multivariable analyses found higher odds of hospitalization (odds ratio [OR]=2.8, 95% confidence interval [CI]: 1.5-5.1), ICU admission (OR=4.2, 95% CI: 1.9-9.1), and need for respiratory support (OR=4.2, 95% CI: 2.0-8.8) among CAYA-DS. Modifications to cancer-directed therapy were more common among CAYA-DS when related to neutropenia (p=.001), but not when unrelated to neutropenia (p=.88); CAYA-DS did not have higher odds of changes to cancer-directed therapy (OR=1.20, 95% CI: 0.7-2.1). We identify CAYA-DS with hematologic malignancies as a vulnerable subpopulation at greater risk for severe COVID-19 infection. This can inform conversations with patients and families regarding therapeutic and preventive measures, as well as the risks and benefits of modifying chemotherapy in the setting of COVID-19.

Pleasurable and problematic receptive anal intercourse and diseases of the colon, rectum and anus.

The ability to experience pleasurable sexual activity is important for human health. Receptive anal intercourse (RAI) is a common, though frequently stigmatized, pleasurable sexual activity. Little is known about how diseases of the colon, rectum, and anus and their treatments affect RAI. Engaging in RAI with gastrointestinal disease can be difficult due to the unpredictability of symptoms and treatment-related toxic effects. Patients might experience sphincter hypertonicity, gastrointestinal symptom-specific anxiety, altered pelvic blood flow from structural disorders, decreased sensation from cancer-directed therapies or body image issues from stoma creation. These can result in problematic RAI - encompassing anodyspareunia (painful RAI), arousal dysfunction, orgasm dysfunction and decreased sexual desire. Therapeutic strategies for problematic RAI in patients living with gastrointestinal diseases and/or treatment-related dysfunction include pelvic floor muscle strengthening and stretching, psychological interventions, and restorative devices. Providing health-care professionals with a framework to discuss pleasurable RAI and diagnose problematic RAI can help improve patient outcomes. Normalizing RAI, affirming pleasure from RAI and acknowledging that the gastrointestinal system is involved in sexual pleasure, sexual function and sexual health will help transform the scientific paradigm of sexual health to one that is more just and equitable.

Abstract PO5-12-10: Eyebrow and eyelash loss in breast cancer survivors

Abstract Background: Eyebrow and eyelash loss, known as madarosis, can occur secondary to breast cancer-directed therapy. However, the incidence and predictors of this phenomenon are not well-known. The purpose of this study is to ascertain the proportion of breast cancer survivors who experience madarosis, potential contributing factors to eyebrow and eyelash loss, and associations between this symptom and mental health. Methods: Breast cancer survivors were invited to participate in an ongoing longitudinal cohort study, the Mayo Clinic Breast Disease Registry (MCBDR), after having been seen at least once for breast cancer at Mayo Clinic in Rochester, MN. Those who consented were mailed a survey approximately one year after diagnosis. Respondents were asked to report their degree of eyebrow and eyelash loss experienced since their diagnosis on a 4-point scale of “no loss” (0) to “complete loss” (3). The proportions of participants who reported eyebrow and eyelash loss were evaluated overall and according to treatment type by descriptive statistics. Relationships between eyebrow and eyelash loss and mental health scores collected using the PROMIS-10 project scales (ranging from 0-20), with the poorest mental health indicated by scores under 8, were explored. Results: 838 registry participants responded to the year 1 survey’s alopecia questions. The median age of breast cancer survivors was 59.4 years (range 22-100 years). The majority were diagnosed at stage I-II (69%). 315 (37%) had received chemotherapy (+/- endocrine therapy), 415 (50%) had received endocrine therapy only, and 108 (13%) had received neither. Nearly half reported eyebrow loss (49%) or eyelash loss (49%). Eyebrow loss was reported by 89% of chemotherapy recipients, 27% of endocrine therapy only recipients, and 19% of those not treated with chemotherapy or endocrine therapy. 102 (32%) of those with chemotherapy-associated eyebrow loss reported that it was complete. Eyelash loss was reported by 274 (87%) of chemotherapy recipients, 112 (27%) of endocrine therapy only recipients, and 23 (21%) of those who received neither. Although no formal statistical testing was performed, there was a numerically higher proportion of patients with eyebrow and/or eyelash loss who reported poor mental health. Conclusions: Madarosis is a bothersome symptom in cancer survivors, particularly after chemotherapy. Future investigation into the incidence, predictors, and treatment of anti-neoplastic medication-related madarosis is needed. Table. Global mental health scores on PROMIS scale for eyebrow and eyelash loss Citation Format: Sarah Premji, Kathryn Ruddy, Nicole Larson, Charles Loprinzi, Brittany Dulmage, Maryam Lustberg, Fergus Couch, Janet Olson, Elizabeth Cathcart-Rake. Eyebrow and eyelash loss in breast cancer survivors [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-12-10.

Palliative care for patients with gastroesophageal cancer at all stages: a narrative review.

Gastroesophageal junction (GEJ) cancer is a highly morbid disease with a poor prognosis. While uncommon in the United States, globally it is ranked as the sixth or seventh most common cancer depending on survey tool. GEJ cancer presents a unique and challenging symptom profile for patients at all disease stages, regardless of histology. Even patients with early stage disease experience debilitating cancer-related symptoms and treatment side effects. The heavy symptom burden associated with this disease includes dysphagia, nausea and vomiting, pain, anxiety, depression and malnutrition. These symptoms require a multidisciplinary approach involving local therapies including radiation and stent placement, systemic cancer-directed therapy, nutritional support, and supportive medical management. This review aims to examine the unique symptom burden experienced by patients with GEJ cancer and provide an updated overview of symptom management techniques. A PubMed search was conducted using the terms "gastroesophageal junction cancer AND palliative care". Articles published from 2008 to 2022 with a primary focus on supportive care for patients with GEJ cancers were reviewed. A total of 119 articles were identified and screened in our database search. Of these, 22 full text articles met inclusion criteria and were reviewed. Seventeen articles addressed technical interventions for the alleviation of dysphagia, 1 article focused on nutrition, 1 article described the impact of multidisciplinary tumor boards, 1 article presented the effect of home nurse visits, 1 article described the use of antiemetics, and 1 article was a narrative review of supportive care. In this narrative review, we examine specific supportive care needs in the GEJ cancer population. While the predominant symptom addressed in the literature is dysphagia, patients with GEJ cancer carry a complex symptom burden from diagnosis, through cancer-directed therapy to end-of-life care. Early referral to specialty palliative care should be considered for all patients with GEJ cancer to foster symptom management and delivery of goal concordant care.

Investigating the safety and feasibility of osteopathic manipulative medicine in hospitalized children and adolescent young adults with cancer.

Children and adolescents young adults (AYAs) undergoing treatment for oncologic diagnoses are frequently hospitalized and experience unwanted therapy-induced side effects that diminish quality of life. Osteopathic manipulative treatment (OMT) is a medical intervention that utilizes manual techniques to diagnose and treat body structures. Few studies have investigated the implementation of OMT in the pediatric oncology outpatient setting. To date, no studies have investigated the safety and feasibility of OMT in the pediatric oncology inpatient setting. The objective of this study is to investigate the safety and feasibility of OMT in the pediatric oncology inpatient setting. This is a prospective, single-institution pilot study evaluating children and AYAs aged≥2 years to≤30 years with a diagnosis of cancer hospitalized at Riley Hospital for Children (RH) from September 2022 to July 2023. Approval was obtained from the Indiana University Institutional Review Board (IRB). Patients were evaluated daily with a history and physical examination as part of routine inpatient management. Patients who reported chemotherapy side effects commonly encountered and managed in the inpatient setting, such as pain, headache, neuropathy, constipation, or nausea, were offered OMT. Patients provided written informed consent/assent prior to receiving OMT. OMT was provided by trained osteopathic medical students under the supervision of a board-certified osteopathic physician and included techniques commonly taught in first- and second-year osteopathic medical school curricula. Safety was assessed by a validated pain (FACES) scale immediately pre/post-OMT and by adverse event grading per Common Terminology Criteria for Adverse Events (CTCAE) 24 h post-OMT. All data were summarized utilizing descriptive statistics. A total of 11 patients were screened for eligibility. All patients met the eligibility criteria and were enrolled in the study. The majority of patients were male (n=7, 63.6 %) with a median age of 18.2 years at time of enrollment (range, 10.2-29.8 years). Patients had a variety of hematologic malignancies including B-cell acute lymphoblastic leukemia (ALL) (n=5, 45.5 %), T-cell ALL (n=1, 9.1 %), acute myeloid leukemia (AML) (n=2, 18.2 %), non-Hodgkin's lymphoma (n=2, 18.2 %), and Hodgkin's lymphoma (n=1, 9.1 %). All patients were actively undergoing cancer-directed therapy at the time of enrollment. There were 40 unique reasons for OMT reported and treated across 37 encounters, including musculoskeletal pain (n=23, 57.5 %), edema (n=7, 17.5 %), headache (n=5, 12.5 %), peripheral neuropathy (n=2, 5.0 %), constipation (n=2, 5.0 %), and epigastric pain not otherwise specified (n=1, 2.5 %). Validated FACES pain scores were reported in 27 encounters. Of the 10 encounters for which FACES pain scores were not reported, 8 encounters addressed lower extremity edema, 1 encounter addressed peripheral neuropathy, and 1 encounter addressed constipation. The total time of OMT was documented for 33 of the 37 encounters and averaged 9.8 min (range, 3-20 min). Hospitalized children and AYAs with cancer received OMT safely with decreased pain in their reported somatic dysfunction(s). These findings support further investigation into the safety, feasibility, and efficacy of implementing OMT in the pediatric oncology inpatient setting and to a broader inpatient pediatric oncology population.