Pai, Tanmayi

592 Background: The introduction of peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) DOTATATE has led to a paradigm shift in the treatment of neuroendocrine tumors (NETs). Hematological toxicity is a well-recognized adverse effect (AE) of 177Lu DOTATATE. Most cytopenias are transient, with an estimated incidence of 10-25%, typically mild to moderate in severity (grade G1-2). The most dreaded AE of PRRT is therapy-related myeloid neoplasm (t-MN), with an estimated 2-8% incidence and a higher incidence reported in patients who also received prior chemotherapy. We sought to evaluate the hematological safety of 177Lu PRRT in the setting of NETs with extensive (i.e., innumerable) bone metastases. Methods: We retrospectively reviewed the medical records of all Mayo Clinic patients (pts) with extensive/innumerable osseous metastases, defined as >50% skeletal involvement by positron emission tomography (PET) DOTATATE, who were treated with 177Lu DOTATATE. Pts characteristics and laboratory results were collected before, during, and after 177Lu DOTATATE treatment. Hematotoxicity was graded according to the NCI-CTCAE v5. Results: Out of 27 pts, 13(48%) developed cytopenia(s) of any grade after treatment with one or more cycles of 177Lu DOTATATE. In total, there were 13(48%) pts with anemia, 13(48%) with thrombocytopenia, and 6(22%) with neutropenia. Six (22%) pts had severe hematological toxicity (G3-4). Twelve months post-PRRT, 7(26%) pts continued to experience cytopenia(s) of any grade, of whom 4(15%) had G3-4 hematotoxicity. One pt developed t-MN, and two pts had myelophthisis on bone marrow biopsy from infiltrating NET. 16(59%) pts received cytotoxic chemotherapy before PRRT, and 7(25.9%) developed subsequent cytopenia(s). Overall, 15(55%) pts completed four cycles, while 3 pts didn’t complete four cycles of 177Lu DOTATATE due to hematotoxicity. Conclusions: Pts with advanced NETs and extensive/innumerable bone metastases treated with PRRT could be at higher risk for myelosuppression than historical controls. Our study highlights the importance of carefully monitoring and assessing hematological parameters in pts being considered for 177Lu DOTATATE with extensive/innumerable bone metastasis. [Table: see text]

269 Background: There are strong data showing that patients (pts) with metastatic non-small cell lung cancer (NSCLC) receiving chemotherapy experience better quality of life (QOL) and longer overall survival (OS) when palliative care (PC) services are integrated early in their treatment course. Therefore, at our cancer center, pts with stage IV NSCLC have been referred to PC by oncology providers. In this study, we evaluated the uptake of PC services, specifically in pts with NSCLC who received immune checkpoint inhibitors (ICIs). ICIs have been considered to have less severe or less frequent adverse effects as compared to chemotherapy, possibly leading to fewer referrals to PC. Methods: We conducted a retrospective review of all pts at the Mayo Clinic Cancer Center in Florida who received single-agent ICI therapy for the treatment of stage IV NSCLC at any point between July 1, 2015, and July 1, 2022. The primary aim was to evaluate the uptake of PC services before or during treatment with ICIs. Descriptive statistics were used to characterize pt demographics and outcomes. Results: 129 pts were identified. 53.4% were male, and 46.6% were female. The majority of pts (84.4%) were white. 62 pts (48.0%) were seen by a PC provider before or during ICI treatment; 41 of these (31.7%) were seen by PC after starting ICI therapy. When grouped by year of ICI initiation, 30/73 pts (41.0%) treated between 2015 and June 2018 were seen by a PC provider, as compared to 15/31 pts (48.3%) treated between July 2018 and June 2020 and 17/25 pts (68.0%) treated between July 2020 and July 2022. Interestingly, the majority of pts who received PC services in the 2020-2022 group (12/17, or 70.5%) were seen by a PC provider for the first time prior to ICI initiation, whereas the majority of pts who received PC services prior to July 2020 (37/45, or 82.2%) were seen by a PC provider for the first time after ICI initiation. The mean number of PC visits increased from 1.59 in the 2015-2018 group to 1.84 in the 2018-2020 group and 4.96 in the 2020-2022 group. Conclusions: Uptake of PC services in pts with stage IV NSCLC receiving single-agent ICIs at our cancer center has increased over time, which is encouraging. Nevertheless, the numbers remain suboptimal, with less than 70% of pts receiving PC services. We plan to develop a multidisciplinary quality improvement project involving implementation of a mechanism to ensure that most patients with stage IV NSCLC, regardless of the type of systemic treatment they receive, are receiving PC services.

e21156 Background: Immunotherapy (IO) is one of the major treatments for patients with metastatic non-small cell lung cancer (mNSCLC). IO may be discontinued in patients for many reasons, the most common being progression of disease (POD). For those patients who discontinued IO for reasons other than POD, such as immune-related adverse event (irAE), there is limited data that compare progression-free survival (PFS) and overall survival (OS) when IO is continued vs. stopped. Methods: We conducted a retrospective study of all patients with mNSCLC (stage IV) treated with IO at our institution from 2011 to 2022. Patients who discontinued IO due to POD were excluded from the analysis. The clinical outcomes, including PFS, OS, and irAE were investigated among patients with no POD who stopped IO prior to 6 or 12 months (m) vs. those that continued IO > 6 or 12m. Results: The analysis at the 6m timepoint included 92 patients, 82.6% were white, 50% were male, 67.4% had adenocarcinoma, and 82.6% used tobacco. The most common site of metastasis was bone (28.3%), followed by CNS (20.7%). 51.2% of patients had received IO as the first line systemic therapy and 32.6% received it as their second. Pembrolizumab was the most used IO (84.78%). Among these patients, 25 discontinued IO before 6m, and 67 patients continued IO beyond 6m. irAE, of any grade, occurred in 44.0% vs 37.3% when comparing IO discontinued with IO continued group at 6m. Patients who continued treatment beyond 6m had a longer duration of PFS (22.8m vs 11.8m, p = 1.14E-04) with a significant increase in OS (34.5m vs 14.0m, p = 1.34E-07). The analysis at the 12m timepoint included 71 patients, 87.3% were white, 46.5% were male, 78.9% had adenocarcinoma, and 80.3% used tobacco. The most common site of metastasis was bone (29.9%), followed by CNS (22.5%). 62.0% of patients had received IO as the first line systemic therapy and 28.7% received it as their second. Pembrolizumab was the most used IO (87.3%). Among these patients, 30 discontinued IO before 12m, and 41 patients continued IO beyond 12m. irAE, of any grade, occurred in 36.7% vs 41.5% when comparing IO discontinued with IO continued group at 12m. Similarly, patients who continued treatment beyond 12m had a longer duration of PFS (28.4m vs 14.2m, p = 1.91E-06) with a significant increase in OS (39.9m vs 17.6m, p = 3.45E-09). Conclusions: We observed that patients with mNSCLC and no POD, who continued IO beyond 6m and 12m, experienced a significant increase in PFS and OS than those who discontinued IO, with more significant increases in those who continued IO past 12m. These findings need to be verified in a larger cohort.

e18883 Background: Women comprise more than 40% of the American workforce, with many women working at the time of a breast cancer diagnosis. Pre-diagnosis psychological distress is a rarely studied factor that may affect cancer survivors’ workforce participation and mental health status post treatment. In this 2-site prospective cohort study, we evaluated return to work (RTW) in breast cancer patients (pts) with and without reported pre-diagnosis stress. Methods: We enrolled 198 female pts at Mayo Clinic in Minnesota and Florida with newly diagnosed stage 0-III breast cancer who worked 35-plus hours/week at time of diagnosis. Pts were screened for eligibility at the intake visit. Eligible pts were emailed a baseline survey at the time of diagnosis, then a follow-up survey at 3 months. Surveys assessed demographics, work factors, treatment, and psychological distress per the validated Kessler Psychological Distress Scale (K6). Primary aims were to assess 1) the impact of pre-diagnosis psychological distress on RTW in pts with a breast cancer diagnosis and 2) the incidence of severe psychological distress (K6 ≥13) in those with and without delay in RTW. Wilcoxon rank sum tests were used to compare pts with and without pre-diagnosis stress at baseline and 3 months. Results: 189 and 142 pts took part in the baseline and 3-month surveys, respectively. Here, 40.7% of enrolled pts reported experiencing one or more major life stressors in the 18 months before diagnosis. At 3 months, 6 of the 75 pts who responded (8.0%) endorsed a delay in RTW after breast cancer diagnosis. Half of these pts (3/75) had reported a pre-diagnosis stressor, revealing no significant difference in time to RTW between the stressed and not-stressed groups. Median K6 at diagnosis in those with delay in RTW was 14 (range, 10-17), significantly higher than the median K6 of 9 in those without delay in RTW (range, 6-23; p = 0.026). 5/6 pts who reported delay in RTW had baseline or 3-month K6 ≥13. There was no significant difference in the number of pts with K6 ≥13 at baseline vs. 3 months (31.2% vs. 21.8%, p = 0.85). Overall, the pt population was well educated and well salaried. Conclusions: Pre-diagnosis psychological distress is prevalent, but it does not seem to be associated with delayed RTW in breast cancer pts; indeed, few pts reported a delay in RTW. Pts with delayed RTW after a breast cancer diagnosis had significantly higher median K6, generally ≥13. Thus, delay in RTW in breast cancer pts may be a surrogate marker of more serious psychological illness. Additional study in a socioeconomically diverse pt population is needed.

Abstract Background: SARS-CoV-2 mRNA vaccines have been demonstrated to have robust and durable humoral immune response in healthy individuals. However, their effectiveness in immunocompromised patients, particularly cancer patients, remains less known. Newer data suggests that cancer patients may not mount adequate protective immune response after vaccination. Methods: A retrospective study of patients ≥ 18 years old who had SARS-CoV-2 spike antibody (anti-S Ab) testing after 2 doses of SARS-CoV-2 mRNA vaccines between 12-90 days at Mayo Clinic between January 1, 2021 and May 10, 2021 was performed. The Elecsys Anti-SARS-CoV-2 S electrochemiluminescence immunoassay (Roche Diagnostics, Switzerland) was used to measure the antibody response. Patients with prior COVID-19 infection and patients on immunosuppressive therapy for an indication other than cancer were excluded. Categorical variables were summarized as frequencies (percentages) and continuous variables were reported as median with range. Wilcoxon signed rank test was used to compare continuous variables between groups and Chi-squared or Fisher’s exact test was used to compare categorical variables. All tests were two-sided with p value < 0.05 considered statistically significant. The analysis was done using R program version 3.6.2. Results: Among 201 patients, 79 had breast cancer, 91 had a hematologic malignancy, 6 had other solid malignancies, and 25 had no history of cancer. All breast cancer patients on endocrine therapy or trastuzumab ± pertuzumab without chemotherapy (n=35) had anti-S Ab titer ≥ 500 U/mL. Patients on cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) appeared to have low level of anti-S Ab with 28.6% (n=4/14) had anti-S Ab titer ≤ 500 U/mL. Patients on chemotherapy also had low levels of anti-S Ab with 47% (n=14/30) having anti-S Ab titers ≤ 500 U/mL. When combining breast cancer patients on endocrine therapy alone or anti-HER2 therapy with patients without history of cancer as an immunocompetent group, there was significantly greater proportion of immunocompetent patients (97%) who had anti-S Ab titer ≥ 500 U/mL compared with only 8% of patients with hematologic malignancy and 55% of patients with solid malignancy on chemotherapy or CDK4/6i (p < 0.001). Using multivariate logistic regression analysis adjusted for age, gender, and vaccine type, patients with solid malignancies and treatment-related cytopenia, including chemotherapy and CDK4/6i, (OR 35.51 [95%CI 8.38-255.25, p < 0.001]) were more likely than immunocompetent patients to have a suboptimal anti-S Ab results ≤ 500 U/mL.Conclusion: A significant number of breast cancer patients on chemotherapies and CDK4/6i had poor humoral responses after SARS-CoV-2 mRNA vaccination. While CDK4/6i is not commonly considered as immunosuppressive therapy, breast cancer patients on CDK4/6i appeared to have suboptimal response to SARS-CoV-2 mRNA vaccine. Our study also highlights the significance of assessing antibody response after COVID-19 vaccines in these vulnerable patients. Citation Format: Saranya Chumsri, Pooja P. Advani, Tanmayi S Pai, Zhou Li, Marites Acampora, Gina A Reynolds, Alvaro Moreno-Aspitia, Christopher P Marquez, Keith L. Knutson. Antibody responses after SARS-CoV-2 mRNA vaccination in breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-23-01.

Hemophagocytic lymphohistiocytosis (HLH) syndrome is a hyperinflammatory state that leads to life-threatening, disproportionate activation of the immune system and may be confused for and concomitantly exist with sepsis. However, its treatment differs from sepsis, requiring early initiation of immunosuppressive treatment. While HLH syndrome is more commonly diagnosed in children, internists and other primary care providers must be familiar with the diagnosis and treatment of adult patients with HLH in the hospital and outpatient setting. In this article, we review the essentials that an internist and other primary care providers managing adult HLH patients should know.

Abstract Background: Multiple studies have identified an association between diagnosis of breast cancer and post-diagnosis psychological distress. Some have taken a step further, identifying predictive markers of distress in diagnosed patients and interventions to minimize post-diagnosis distress. Data regarding pre-diagnosis psychological distress and its impact on surgical decision making and clinical outcomes in the breast cancer population are limited. Here, we assessed pre-diagnosis major life stressors and breast cancer outcomes in a single-center population. Methods: Patients with newly diagnosed stage 0-3 breast cancer seen at Mayo Clinic Florida between June 11, 2018, and October 7, 2019, were included. Prior to their initial visit, patients were administered a voluntary telephone survey regarding the incidence of major life events and stressors during the 18 months preceding their diagnosis. Demographic data including age and ethnicity were also included. Subsequent clinical outcomes were obtained through retrospective chart review. Clinical outcomes were assessed with descriptive statistics. Chi-square tests were used to compare subgroups, with p < 0.05 considered statistically significant. Results: Of 469 patients seen for a new breast cancer diagnosis, 222 patients completed the intake survey and met inclusion criteria. Median age was 60 (27-84) years. 80.6% of patients were white, 7.7% were black, 5.4% were Asian/Pacific Islander, and 2.3% were Latino. Over 95% endorsed having some form of social support. 51.3% reported experiencing a major life event prior to breast cancer diagnosis. Of these patients (n = 114), 43.9% denoted this stressor as family-related, as compared to 20.2% citing non-breast cancer illness, 14.9% claiming relationship stress, and 14% describing employment-related stress. Only 1.8% endorsed stress caused by financial concerns. Multiple major life events were reported by 10.8% of all included patients. Subgroup analysis of the patients with pre-diagnosis stress revealed a similar demographic distribution to the overall sample. Compared to the subgroup without pre-diagnosis stress (n = 108), there were more patients with carcinoma in situ and stage T3/T4 disease (21.1% versus 13.0%, p = 0.11) and 11.4% versus 10.2%, p = 0.77), respectively) in the subgroup with pre-diagnosis stress, although these differences were not statistically significant. More patients with pre-diagnosis stress elected to undergo mastectomy (34.2% versus 22.2%, p = 0.048) as compared to the group without stress. Conclusions: With over half of sample patients reporting pre-diagnosis major life stressors, psychological distress is prevalent prior to breast cancer diagnosis and should be considered as a factor for early intervention, such as psychological and financial counseling, during breast cancer evaluation. The sample population was predominantly white and resource-rich in terms of financial and social support, highlighting a need for characterization of pre-diagnosis psychological distress in more ethnically diverse and/or resource-limited settings. Although additional study is recommended, current data suggest possible associations between pre-diagnosis psychological distress and treatment decision making, particularly the decision to pursue mastectomy. Citation Format: Tanmayi Pai, Laura Vallow, Danushka Seneviratne, Dawn Mussallem, Lauren Cornell. Pre-diagnosis major life stressors and breast cancer outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-46.

e21069 Background: Lobectomy remains the standard of care for definitive management of stage I non-small cell lung cancer (NSCLC). Stereotactic body radiation therapy (SBRT) is considered primarily for patients who were either unwilling to have surgery or deemed to be medically unfit for surgery. Current NCCN guidelines indicate the use of CT for surveillance following curative-intent therapies and recommend CT every 6 months for 2-3 years followed by CT annually without clear guidance on how long to keep doing annual CT scans. This study aims to evaluate the patterns of lung cancer recurrence within and beyond five years post curative therapy. Methods: Patients diagnosed with stage I NSCLC and treated with either curative surgery or SBRT from 1998-2016 at Mayo Clinic Florida were identified. Through retrospective chart review, data was collected on clinical and demographic features, surveillance imaging, pathology, time to recurrence or new primary lung cancer, and location of recurrence (loco-regional vs. distant). Statistical analysis with chi-square test was performed to identify risk factors associated with recurrence. Results: In total, 203 patients with stage I NSCLC were identified with most patients treated with surgery (n = 181) compared with SBRT (n = 22). Median time of follow up is 85 months. Overall, 48 patients (23.6%) developed a recurrence, with the median time to recurrence of 22.3 (3.9-69.8) months. Most recurrences were identified within 5 years from curative therapy (42/48) with 6 patients having a recurrence between 5 and 10 years post curative therapy. Of the 37 patients followed for more than 10 years, there were no recurrences. Twenty seven patients had new primary lung cancers identified and among them, 15 were found within 5 years, 10 found between 5-10 years and 2 found beyond 10 years. Median time to new primary lung cancer was 58.1 months. A positive smoking history and stage IB were found significantly associated with lung cancer recurrence (chi-square test P = 0.007 and P = 0.04 respectively), while age, gender, histology, grade, and treatment type had no association. Conclusions: In this study of 203 patients with stage I NSCLC treated with curative intention, there was no evidence of recurrent disease after 10 years following curative therapy, questioning the utility of continued annual CT surveillance once patients hit this milestone.

529 Background: Multiple prognostic models exist to predict late relapse risk in early stage hormone receptor-positive (HR+) breast cancer (BC). The CTS5 is one such model that has been validated in HR+ HER2-negative BC. The value of this model in HR+ HER2+ has not been established. Here, we assessed CTS5 in patients (pts) with early stage HER2+ BC treated in the NCCTG N9831 (Alliance) trial. Methods: Pts with stage I-III HER2+ HR+ BC who survived ≥ 5 years were included. The online CTS5 calculator was used to determine CTS5 score and risk group (low, intermediate, and high) based on age, tumor size, grade, and number of involved nodes. Kaplan-Meier (KM) estimates, Cox regression models, and C index were used for analysis. Results: From 3,130 pts, 1,204 pts met the criteria and were included. Median age was 49 (22-79) years and median tumor size was 2.4 (0.1-12) cm. 63.6% had grade 3 tumors, 33.6% grade 2, and 2.8% grade 1. Median follow up was 10.89 (5.01-15.32) years. Based on CTS5, 821 (68.2%) pts were classified as high risk, 289 (24%) as intermediate risk, and 94 (7.8%) as low risk. Overall, using univariate Cox regression analysis, there was no statistically significant difference in recurrence free survival (RFS) among pts with intermediate vs. low (HR 0.47 95%CI 0.18-1.22, p = 0.12) and high vs. low (HR1.23 95%CI0.57-2.67, p = 0.6) with the C index of 0.58. Among pts who received concurrent trastuzumab (H) with HR+ BC, there was also no statistical difference in RFS between high vs. low (HR 0.68 95%CI0.24-1.97, p = 0.48) with the C index of 0.55. Paradoxically, pts with intermediate risk had better RFS than low risk (HR 0.18 95%CI0.03-0.97, p = 0.05). As a continuous variable, there is also no significant improvement in RFS per 1 unit increase in CTS5 score (HR 1.19 95%CI 0.73-1.96, p = 0.49) with the C index of 0.54. After 5 years, 7.06% (n = 30/425) of HR+ pts treated with concurrent H recurred. Conclusions: The CTS5 model is not prognostic in pts with early stage HR+ HER2+ BC receiving adjuvant H. While most HR+ HER2+ pts are classified as high risk by CTS5, the recurrence between years 5-10 was low in pts who received adjuvant H. This study highlights the need to develop a new predictive model for risk of late relapse in this specific group of pts to enable clinicians to determine which pts would benefit from extended adjuvant endocrine therapy. Support: BCRF-19-161, U10CA180821, Genentech. https://acknowledgments.alliancefound.org Clinical trial information: NCT00005970 .