Citations

Abstract Background: Extended adjuvant endocrine therapy (eET) beyond the first 5 years of ET improves long-term outcomes in breast cancer survivors. For women who remain premenopausal, evidence for benefit has only been demonstrated to date for 5 years of additional tamoxifen, after an initial 5 years of tamoxifen (from ATLAS, aTTom). There are no data available for eET among premenopausal women treated with initial adjuvant aromatase inhibition (AI) and ovarian functions suppression (OFS). Thus, there is uncertainty regarding the optimal eET regimen for young breast cancer survivors. Methods: The Young Women’s Breast Cancer Study (YWS) is a multicenter prospective cohort of women age ≤40 years newly diagnosed with breast cancer between 2006-2016. Women with stage I-III hormone receptor positive breast cancer, ≥6 years post-diagnosis without breast cancer recurrence were considered candidates for eET. Use of eET was elicited on surveys completed at 6, 7 and/or 8 years post-diagnosis, censoring for recurrence or death. Those completing ≥1 survey were eligible for analysis. Patient characteristics were compared by Chi-square test between eET users and non-users, and logistic regression applied to identify factors associated with eET use. Results: Of 667 potential eET candidates, 73.9% (493/667) returned ≥1 survey between year 6-8 and were eligible for analysis. Compared to those without a year 6-8 survey, the analytic cohort tended to be more non-Hispanic white (86.0% v. 77.6%), more financially comfortable (53.9% v. 39.5%) and more likely to have children pre-diagnosis (59.6% v. 41.4%); age and disease characteristics were similar. Overall, 59.6% (294/493) reported any eET use, with use declining over time from 56.9% (265/466) to 51.4% (219/426) to 46.8% (162/346) at years 6, 7 and 8 post-diagnosis, respectively. Among eET users (n=294), tamoxifen monotherapy was the most common approach (76.9%, 226/294), followed by AI monotherapy (22.1%, 65/294, presumably women who transitioned into menopause), AI-OFS (7.1%, 21/294) and tamoxifen-OFS (3.1%, 9/294). Women diagnosed after 2012 were as likely to receive eET as those diagnosed 2006-2011 (59.4%, 117/197 v. 59.8%, 177/296 p=0.928), however eET more often included AI, with or without OFS (41.0% v. 18.6%, p<0.001), or OFS (17.9% v. 7.3%, p=0.005) in later years. In multivariable analysis, increasing age (per year odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.15, p<0.001), higher stage (II v. I: OR: 2.85, 95% CI: 1.81-4.48, p<0.001; III v. I: OR: 3.73, 95% CI: 1.87-7.42, p<0.001) and receipt of chemotherapy (OR: 3.50, 95% CI: 2.08-5.91, p<0.001) were independently significantly associated with any eET use, while women not of white non-Hispanic race/ethnicity were less likely to report eET use (OR: 0.49, 95% CI: 0.28-0.87, p=0.014). Rates of pregnancy in years 1-5 did not differ between eET users and non-users (10.0%, 29/291 v. 8.7%, 17/195, p=0.645) Conclusion: The majority of eligible young breast cancer survivors in the YWS have received eET despite limited data regarding its utility in this population. Heterogeneity exists regarding strategies utilized, and while some factors associated with eET use appear to reflect appropriate risk-based care, such as stage and receipt of chemotherapy, others, including age and race, suggest disparate uptake. Clinical studies are needed in order to determine the optimal approach to eET for young women with a history of early stage hormone receptor-positive breast cancer who remain premenopausal following 5 years of ET. Ensuring risk and preference-based uptake of eET should be a priority. Citation Format: Tal Sella, Yue Zheng, Shoshana M Rosenberg, Kathryn J Ruddy, Shari I Gelber, Rulla M Tamimi, Jeffrey M Peppercorn, Lidia Schapira, Virgina F Borges, Steven E Come, Lisa A Carey, Eric P Winer, Ann H Partridge. Extended adjuvant endocrine therapy in a longitudinal cohort of young breast cancer survivors [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 PD13-10.

Abstract Background: Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China.Methods: After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021.Results: There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.3 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%) and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far.Conclusions: There has been increasing number of patients with BHDS recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.

Abstract Alveolar macrophages (AMs) are major lung tissue-resident macrophages capable of proliferating and self-renewal in situ. AMs are vital in pulmonary antimicrobial immunity and surfactant clearance. The mechanisms regulating AM compartment formation and maintenance remain to be fully elucidated currently. In this study, we have explored the roles of mitochondrial transcription factor A (TFAM)–mediated mitochondrial fitness and metabolism in regulating AM formation and function. We found that TFAM deficiency in mice resulted in significantly reduced AM numbers and impaired AM maturation in vivo. TFAM deficiency was not required for the generation of AM precursors nor the differentiation of AM precursors into AMs, but was critical for the maintenance of AM compartment. Mechanistically, TFAM deficiency diminished gene programs associated with AM proliferation and self-renewal and promoted the expression of inflammatory genes in AMs. We further showed that TFAM-mediated AM compartment impairment resulted in defective clearance of cellular debris and surfactant in the lung and increased the host susceptibility to severe influenza virus infection. Finally, we found that influenza virus infection in AMs led to impaired TFAM expression and diminished mitochondrial fitness and metabolism. Thus, our data have established the critical function of TFAM-mediated mitochondrial metabolism in AM maintenance and function.

SummaryThere have been no large studies comparing reduced‐intensity/non‐myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T‐cell non‐Hodgkin lymphoma (T‐NHL) patients undergoing allogeneic transplant (allo‐HCT). A total of 803 adults with peripheral T‐cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T‐cell lymphoma (age 18–65 years), undergoing allo‐HCT between 2008–2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79–1.29; p = 0.95). Similarly, non‐relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61–1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98–1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92–1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3–4 acute graft‐versus‐host disease (HR = 0.67; 95% CI = 0.46–0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo‐HCT for T‐cell NHL.

AbstractPurposeThe Leksell Gamma Knife Icon unit (IU) was introduced recently as an upgrade to the Perfexion unit (PU) at our Gamma Knife practice. In the current study, we sought mainly to characterize dosimetry and targeting accuracy of the IU treatment deliveries using both invasive frame and frameless treatment workflows.MethodsRelative output factors were measured by delivering single‐shot 4, 8 and 16 mm radiation profiles in the manufacturer's acrylonitrile butadiene styrene spherical phantom in coronal and sagittal planes using EBT3 film. Resultant dosimetry was compared with the manufacturer's dose calculation and derived output factors were compared with the manufacturer's published value. Geometric consistency of stereotactic coordinates based on cone‐beam computed tomography (CBCT) versus the traditional conventional CT‐based method was characterized using a rigid phantom containing nine fiducial indicators over four separate trials. End‐to‐end (E2E) testing using EBT3 film was designed to evaluate both dosimetric and geometric accuracy for hypothetical framed and frameless workflows.ResultsRelative output factors as measured by the manufacturer were independently confirmed using EBT3 film measurements to within 2%. The mean 3D radial discrepancy in stereotactic space between CBCT and CT‐based definition over the sampled locations in our rigid geometry phantom was demonstrated to be between 0.40 mm and 0.56 mm over the set of trials, larger than prior reported values. E2E performed in 2D demonstrates sub‐mm (and typically < 0.5 mm) accuracy for framed and frameless workflows; geometric accuracy of framed treatments using CBCT‐defined stereotactic coordinates was shown to be slightly improved in comparison with those defined using conventional CT. Furthermore, in phantom, frameless workflows exhibited better accuracy than framed workflows for fractionated treatments, despite large magnitudes of introduced interfraction setup error. Accuracy of dosimetric delivery was confirmed in terms of qualitative comparisons of dose profiles and in terms of 2D gamma pass rates based on 1%/1 mm criteria.ConclusionThe IU was commissioned for clinical use of frameless and framed treatment protocols. The present study outlines an extensive E2E methodology for confirmation of dosimetric and geometric treatment accuracy.

Objective: Robust disease and syndromic surveillance tools are underdeveloped in the United States, as evidenced by limitations and heterogeneity in sociodemographic data collection throughout the COVID-19 pandemic. To monitor the COVID-19 pandemic in Minnesota, we developed a federated data network in March 2020 using electronic health record (EHR) data from 8 multispecialty health systems. Materials and Methods: In this serial cross-sectional study, we examined patients of all ages who received a COVID-19 polymerase chain reaction test, had symptoms of a viral illness, or received an influenza test from January 3, 2016, through November 7, 2020. We evaluated COVID-19 testing rates among patients with symptoms of viral illness and percentage positivity among all patients tested, in aggregate and by zip code. We stratified results by patient and area-level characteristics. Results: Cumulative COVID-19 positivity rates were similar for people aged 12-64 years (range, 15.1%-17.6%) but lower for adults aged ≥65 years (range, 9.3%-10.7%). We found notable racial and ethnic disparities in positivity rates early in the pandemic, whereas COVID-19 positivity was similarly elevated across most racial and ethnic groups by the end of 2020. Positivity rates remained substantially higher among Hispanic patients compared with other racial and ethnic groups throughout the study period. We found similar trends across area-level income and rurality, with disparities early in the pandemic converging over time. Practice Implications: We rapidly developed a distributed data network across Minnesota to monitor the COVID-19 pandemic. Our findings highlight the utility of using EHR data to monitor the current pandemic as well as future public health priorities. Building partnerships with public health agencies can help ensure data streams are flexible and tailored to meet the changing needs of decision makers.