Prior Smokers Research Articles

8425 Cancer Risk in Transgender Veterans Undergoing Gender-Affirming Hormone Therapy in a Single Medical Center

Abstract Disclosure: A. Vanasco: None. A. Chitnavis: None. K.L. Vinales: None. R.R. Correa: None. Background: The risk of cancer in the transgender patients while on Gender Affirming Therapy is still a source of safety concern among healthcare professionals. We aimed to assess the cancer incidence and potential risk factors in this population. Methods: An initial cohort of 428 charts within the Phoenix VA Healthcare System from January 1990 through October 2023 were identified using ICD codes consistent with a diagnosis of gender dysphoria. From this initial cohort, we completed a chart review of 94 patients who received GAHT through the endocrinology department. The collected information included type of cancer diagnosis, self-reported GAHT start date if not at the Phoenix VA, and risk factors for cancer (HPV, HIV, smoking history) along with recommended cancer screening, like latest mammogram, pap smear, and colonoscopy. Results: We identified 67 transgender women and 27 transgender men, 53.8± 16.0 and 43.8 years ± 12.6 years-old, with an average of 10 years of GAHT (10.1±7.4 years for estradiol therapy and 10.2±4.4 years for testosterone therapy, range 0.5-44 years of use). Cancer was diagnosed in 18 (27.7%) transgender women, including 8 skin, 3 lung, 2 prostate, 2 tongue, 1 thyroid, 1 musculoskeletal, 1 sinus, 1 bladder cancer. Among our transgender women, 37% were current and 33% were prior smokers. Two (3.0%) were HPV positive and both had cancer diagnoses, while two (3.0%) were HIV positive and neither had a cancer diagnosis. 19 (28.4%) underwent colonoscopies with benign results and 48 (71.6%) were untested. 21 (31.3%) underwent mammograms with benign findings, 1 (1.5%) had a mastectomy and reconstruction, and 45 (67.2%) were untested. Cancer was diagnosed in 3 (10.3%) transgender men, and included 2 skin, 1 breast, 1 cervical cancer. 4 (14.8%) were HPV positive, none of which had cancer. Forty percent of the transgender men were active smokers and an additional 30% were prior smokers. None were HIV positive. 8 (29.6%) underwent colonoscopy, 7 of which were benign and 1 pending results, and 19 (70.1%) were untested. Three (11.1%) underwent mammograms with benign findings, 16 (59.3%) had bilateral mastectomies, and 8 (29.6%) were untested. Eleven (40.7%) had pap smears with 10 benign findings and 1 ASCUS, 11 (40.7%) had hysterectomies, and 5 (18.5%) were untested. Conclusion: Our study sheds light on cancer incidence in transgender veterans undergoing GAHT. Incidence of cancer was higher in transgender women than transgender men, and the leading type of cancer for both groups was of the skin, not considered a GAHT risk. Significant numbers of both transgender men and women did not receive recommended health screenings, highlighting the need for improved education of screening importance. Presentation: 6/2/2024

Smoking cessation prior to elective total joint arthroplasty results in sustained abstinence postoperatively.

Tobacco use is a well-documented modifiable risk factor for perioperative complications. To determine the tobacco abstinence rates of patients who made cessation efforts prior to a total joint arthroplasty (TJA) procedure. A retrospective evaluation was performed on 88 self-reported tobacco users who underwent TJA between 2014-2022 and had tobacco cessation dates within 3 mo of surgery. Eligible patients were contacted via phone survey to understand their tobacco use pattern, and patient reported outcomes. A total of 37 TJA patients participated. Our cohort was on average 61-years-old, 60% (n = 22) women, with an average body mass index of 30 kg/m2. The average follow-up time was 2.9 ± 1.9 years. A total of 73.0% (n = 27) of patients endorsed complete abstinence from tobacco use prior to surgery. Various cessation methods were used perioperatively including prescription therapy (13.5%), over the counter nicotine replacement (18.9%), cessation programs (5.4%). At final follow up, 43.2% (n = 16) of prior tobacco smokers reported complete abstinence. Patients who were able to maintain cessation postoperatively had improved Patient-Reported Outcomes Measurement Information System (PROMIS)-10 mental health scores (49 vs 58; P = 0.01), and hip dysfunction and osteoarthritis outcome score for joint replacement (HOOS. JR) scores (63 vs 82; P = 0.02). No patients in this cohort had a prosthetic joint infection or required revision surgery. We report a tobacco cessation rate of 43.2% in patients undergoing elective TJA nearly 3 years postoperatively. Patients undergoing TJA who were able to remain abstinent had improved PROMIS-10 mental health scores and HOOS. JR scores. The perioperative period provides clinicians a unique opportunity to assist active tobacco smokers with cessation efforts and improve postoperative outcomes.

Pulmonary toxicities in patients (pts) with metastatic breast cancer (mBC) treated with trastuzumab deruxtecan (T-DXd): The Mayo Clinic experience.

11145 Background: T-DXd is increasingly used in mBC. A T-DXd toxicity of special interest is interstitial lung disease/pneumonitis (ILD), occurring in 10-15% of pts in the DESTINY-Breast trials, and with potential lower incidence/severity in earlier line settings [Krop et al, ASCO 2023]. However, in routine practice, T-DXd may be used in pts with more heavily pre-treated mBC and previously exposed to other antibody-drug conjugates (ADC) [Premji et al SABCS 2023]. We evaluated the incidence/severity of T-DXd related ILD in mBC at Mayo Clinic. Methods: We retrospectively identified pts with mBC who received ≥1 dose of T-DXd at Mayo Clinic, Rochester, MN, between July 2022-December 2023. Demographic, mBC, and pulmonary clinical variables were abstracted from the clinical records. Data was summarized using descriptive statistics. Diagnosis of ILD was determined by treating clinicians, and severity to CTCAE V5 based on clinical documentation. Results: 77 pts with mBC received T-DXd during the study period. All were female, the majority (70, 91%) were Caucasian, and median age was 58. 53 (69%) had HER2-low mBC (37 HR+, 16 HR-) and 24 (31%) had HER2+ mBC (17 HR+, 7 HR-). 31 (40%) were active or former smokers. 11 (14%) had pulmonary comorbidities, including 6 (7.8%) with asthma, 2 (2.6%) with prior pneumonitis, and 3 (3.9%) with other pulmonary comorbidities. They had previously received a median of 1 line of endocrine therapy, and 4 lines of chemotherapy, with 20 (26%) having received another ADC. 17 (22%) developed any grade ILD [G1: 3 (4%), G2: 7 (9%), G3: 2 (3%), G4: 1 (1%), G5: 4 (5%)]. Among pts with ILD of any grade, 13 (76.5%) presented with at least 1 symptom (cough/SOB). The median number of T-DXd cycles prior to onset of any grade ILD was 6 (range 2-13), or 18 (range 6-39) weeks. 5 (29%) pts with any grade ILD received a prior ADC. Of pts with ≥G3 ILD (n=7), all were Caucasian, 2 (30%) were prior smokers, none had prior lung disease, and had received a median of 5 prior lines of chemo, with 4 (57%) having received a prior ADC. All grade ≥2 ILDs were treated with systemic steroids, and 1 also received IVIG. CT chest was used for diagnosis of all ILD. 7 pts (41%) required hospitalization, all of whom had bronchoscopy, with 5 (29%) requiring intubation. All pts with G1 ILD (3, 18%) restarted T-DXd without ILD recurrence. Conclusions: In this case series,22% of ps treated with T-DXd experienced ILD (5% G5), higher than the rate observed in the pivotal DESTINY-Breast trials, possibly due to real-world use of T-DXd in more heavily pre-treated pts and in pts with pulmonary comorbidities.

Effects of clinical covariates on serum miRNA expression among women without ovarian cancer.

Serum microRNAs (miRNAs) are potential biomarkers for ovarian cancer; however, many factors may influence miRNA expression. To understand potential confounders in miRNA analysis, we examined how sociodemographic factors and comorbidities, including known ovarian cancer risk factors, influence serum miRNA levels in women without ovarian cancer. Data from 1,576 women from the Mass General Brigham Biobank collected between 2012 and 2019, excluding subjects previously or subsequently diagnosed with ovarian cancer, were examined. Using a focused panel of 179 miRNA probes optimized for serum profiling, miRNA expression was measured by flow cytometry using the Abcam Fireplex® assay and correlated with subjects' electronic medical records. The study population broadly reflected the New England population. The median age of subjects was 49 years, 34% were current or prior smokers, 33% were obese (BMI >30kg/m2), 49% were postmenopausal, and 11% had undergone prior bilateral oophorectomy. Significant differences in miRNA expression were observed among ovarian risk factors such as age, obesity, menopause, BRCA1 or BRCA2 germline mutations or breast cancer in family history. Additionally, miRNA expression was significantly altered by prior bilateral oophorectomy, hypertension, and hypercholesterolemia. Other variables, such as smoking, parity, age at menarche, hormonal replacement therapy, oral contraception, breast, endometrial, or colon cancer, and diabetes were not associated with significant changes in the panel when corrected for multiple testing. Serum miRNA expression patterns are significantly affected by patient demographics, exposure history, and medical comorbidities. Understanding confounders in serum miRNA expression is important for refining clinical assays for cancer screening.

The natural history of isolated common femoral endarterectomy for chronic limb-threatening ischemia

ObjectiveOcclusive disease of the common femoral artery can generate profound lower extremity ischemia as the normal collateral pathways from the profunda to the superficial femoral artery cannot adequately develop. In patients with lifestyle-limiting claudication, isolated common femoral endarterectomy (CFE) is highly effective. Because CFE does not provide direct, in-line flow to the plantar arch, it has been felt to provide inadequate revascularization to patients with chronic limb-threatening ischemia (CLTI). The purpose of this retrospective clinical study was to report and assess the natural history of selected patients with CLTI treated with isolated CFE (without concomitant infrainguinal revascularization). MethodsConsecutive CFEs performed in a large, urban hospital for CLTI between 2014 and 2021 were reviewed. Patient characteristics, limb, and anatomical stages using the Wound, Ischemia, foot Infection (WIfI) and Global Limb Anatomic Staging System were tabulated. Limb-specific and survival-related end points were analyzed. ResultsFifty-eight patients presenting with CLTI underwent isolated CFE (mean age, 74 ± 10 years; 62% male, 90% current or prior smoker). Comorbidities included diabetes (52%), coronary artery disease (55%), congestive heart failure (22%), and end-stage renal failure on hemodialysis (5%). Patients presented with either rest pain (36%) or tissue loss (64%); the latter group exhibited advanced limb threat (68% in WIfI stage 3 or 4). The majority of patients had associated severe infrainguinal disease (50% Global Limb Anatomic Staging Systems 3). After a median follow-up of 17 months (range, 10-29 months), vascular reintervention was required in 7 patients (12%). One patient (2%) required major limb amputation after presentation in WIfI stage 4 (W3I3fI0). Indeed, WIfI stage 4 was a significant univariate predictor of the need for subsequent infrainguinal bypass (P = .034). ConclusionsIsolated CFE as primary therapy in highly selected patients with CLTI was safe and effective. Index limb stage is predictive of the need for associated infrainguinal revascularization in this complex population.

Abstract TP29: Neurodegenerative Plasma Biomarker Associations With Cognitive Resilience in Adults With High White Matter Hyperintensity Volume: A Post-Hoc Analysis of Systolic Blood Pressure Intervention Trial Memory & Cognition in Decreased Hypertension (SPRINT MIND)

Introduction: Although high cerebral white matter hyperintensity volume (WMHv) is associated with cognitive decline, many adults with high WMHv show no cognitive deficits. Neurodegenerative plasma biomarkers may be associated with cognitive decline via vascular processes causing higher WMHv such as cerebral amyloid angiopathy & inflammatory small vessel disease. We determined associations of plasma amyloid β 42 (AB42), amyloid β 40 (AB40), AB42/AB40, total tau, & neurofilament light chain (NfL) with cognitive resilience (CR) in adults with high WMHv using baseline MRIs & measurements from SPRINT MIND. Methods: This study included baseline data from 186 SPRINT MIND participants who were in the highest WMHv tertile & had available plasma biomarker concentrations & Montreal Cognitive Assessment (MoCA) scores. We defined CR two ways: A) MoCA score >25 or B) MoCA score >22. We determined univariate & adjusted odds ratios (OR) & 90% confidence intervals (CI) for each aforementioned plasma biomarker with CR. Confounders in adjusted models were: age, sex, race-ethnicity (Non-Hispanic white, Non-Hispanic Black, Hispanic, or other) education (no college education, college education, or post-graduate education), smoking history (never smoker, prior smoker, or current smoker) physical activity (0, 1-4, or ≥ 5 days of vigorous physical activity), diabetes, having insurance, & average systolic blood pressure. Residual confounding and effect modification by WMHv were tested in sensitivity analyses. Results: In our sample, the mean age was 72.6 years, 45.7% were female & 66% were Non-Hispanic white. The median WMHv was 10.0 cm 3 (25%-75% range: 6.3 - 16.9 cm 3 ). . CR defined as MoCA scores > 25 & >22 was present in 28.5% & 56.5% of participants respectively. Lower plasma AB40 was marginally associated with CR using a MoCa cutoff of >25 (OR 1.003, 90% CI: 1.001-1.006) in univariate analyses. There were no other significant (P>0.1) univariate or adjusted associations between plasma biomarkers with CR using either MoCa cutoff, nor significant confounding or effect modification by WMHv (P> 0.1). Conclusion: There were no significant adjusted associations between any plasma biomarker with CR. Future work should identify factors associated with CR in adults with high WMHv.

Examining the effect of COVID-19 on hypertrophic cardiomyopathy hospitalizations in the USA: a nationwide propensity-score matched analysis

Abstract Background Impact of COVID-19 infection in patient with underlying cardiovascular conditions has been widely studied, but its impact in patients with cardiomyopathies like hypertrophic cardiomyopathy (HCM) still lack data leading to this population-based analysis. Methods We queried the National Inpatient Sample (2020) to identify adult hospitalizations with HCM in patients with vs without COVID-19. Baseline characteristics, comorbidities, and outcomes of HCM-related admissions with vs. without COVID-19 were analyzed on a propensity score matched [1:2 ratio] sample controlled for age, sex, race, income quartile, insurance payer type, and discharge quarter. Multivariate logistic regression was used to assess the impact of COVID-19 on all-cause mortality and major adverse cardiac events (MACE), a composite of Atrial Fibrillation (AF), Cardiac arrest, and Acute ischemic stroke (AIS). Results After exclusion of samples with missing data, 50400 HCM related hospitalizations were recorded in 2020 of which 2005 (4.0%) had COVID-19. 1:2 propensity matched analysis led to two HCM cohorts, 1970 patients with COVID-19 and 3905 without COVID-19 (Table 1). Of all HCM related admissions, the COVID-19 group comprised majorly of Hypertension (81.5% vs 76.2%; all p<0.001), diabetes (40.9% vs 34.8%; all p<0.001), Obesity (25.9% vs 22.8%; p=0.0090). However, had less burden of Peripheral vascular disease (6.9% vs 10.8%), prior coronary artery bypass graft (3.05 vs 5.0%), smoker (22.3% vs 28.8%), Alcohol abuse (1.8% vs 4.0%) and drug abuse (1.0% vs 3.3%); all p<0.001. In terms of outcome, the length of stay [days, median (IQR); 12(6-3) vs 7 (4-2)] and cost [median (IQR); $120777(54298-30976) vs 111138 (51450-25636)]; all p<0.001 was significantly higher in COVID-19 cohort compared to non-COVID-19 cohort. The HCM cohort admitted with COVID-19 had significantly higher all-cause mortality (15.7% vs 3.8% p<0.001) and cardiac arrest, including ventricular fibrillation (4.6% vs 2.6%; p<0.001) compared to non-COVID-19 patients. However, interestingly, the COVID-19 group revealed lower rates of AF (36.8% vs 41.5) and AIS (2.5% vs 5.9%) in HCM hospitalization compared to non-COVID-19 group; all p<0.001. Multivariate odds revealed nearly 4 times higher risk of all-cause mortality [OR 4.08, 95%CI (2.59-6.42), p<0.001] in the COVID-19 group. However, odd of AF [OR, 95% CI; 0.76 (0.58-1.00), P<0.04] and AIS [OR, 95% CI; 0.41 (0.19-0.89), P<0.02] related admissions were lower which could be attributed to lockdowns due to the pandemic rather than lower risk of these events. Conclusion This large-scale nationwide analysis revealed that HCM patients who were infected with SARS-CoV-2 infection had nearly four times higher odds of all-cause mortality with lower probability of admissions with AF and AIS. Long-term prospective studies are warranted to validate these findings and longitudinal outcomes in HCM patients infected with COVID-19, especially following vaccination.

Effect of Smoking Cessation on the Risk of Subarachnoid Hemorrhage: A Nested Case-Control Study in Korean Men.

Smoking is a well-established risk factor for subarachnoid hemorrhage (SAH), and current smokers have an increased risk of SAH. However, there are insufficient data on whether smoking cessation in current smokers reduces the risk of SAH. A nested case-control study was conducted based on the National Health Insurance Service-National Health Screening Cohort, which comprises nationwide health claims data and a national health screening program in Korea (2002-2019). We constructed a cohort of current male smokers without a history of stroke at the baseline health screening (2002-2003). From this cohort, cases were defined as individuals who experienced a nontraumatic SAH during the follow-up period up to 2019. Five controls were matched to each case using incidence density sampling. Smoking status (continuation or cessation) before the occurrence of SAH was evaluated using the repeated national health screening program. We conducted a multivariable conditional logistic regression analysis, adjusting for alcohol consumption, physical activity, body mass index, systolic blood pressure, and fasting blood glucose levels, to evaluate the association between SAH risk and smoking cessation. At baseline, there were 112 142 current male smokers. After excluding individuals with prior stroke or insufficient data, the cohort consisted of 105 223 eligible participants (mean age, 50.3±8.5 years). Among them, we identified 318 cases of SAH and 1590 matched controls. Those who quit smoking had a significantly lower risk of SAH compared with current smokers (adjusted odds ratio, 0.55 [95% CI, 0.41-0.73]). The risk of SAH decreased with a longer period of smoking cessation. The risk reduction with smoking cessation was consistent even among prior heavy smokers. Smoking cessation in current male smokers reduced the risk of SAH, and the risk reduction was greater as the cessation period increased. These findings warrant intensive efforts to encourage smokers, even heavy smokers, to quit.

Opioid prescribing patterns for head and neck cancer radiation patients, with a comparison to breast cancer radiation patients.

e18051 Background: Curative-intent radiation treatment for head and neck cancer (HNC) is painful and often requires opioids. Opioid prescribing patterns and duration are not known for these patients. Identifying patients using high amounts of opioids may permit targeted interventions to reduce overall opioid usage. Methods: This retrospective observational study collected EMR prescription data on 10755 patients with a diagnosis of HNC, along with 15664 patients with a diagnosis of breast cancer (BC), between 2008-2022 at Stanford. We identified every non-IV opioid and adjunctive medicine (e.g. gabapentin) prescription using the Stanford Research Repository (STARR). We analyzed opioid prescriptions in 894 HNC and 1100 BC patients who received definitive or adjuvant radiation for 4-6 weeks, and compared usage by age, gender, and ethnicity. A multivariate logistic regression was used to estimate the odds ratio of prescribing opioids, adjusting for age, gender, race, ethnicity, insurance type, and substance use history. Results: HNC patients prescribed opioids were 69% male; 66% white, 17% Asian; median age of 65.9 years (IQR: 56.9-73.9); 48% prior smokers and 2% reported prior heavy drinking. 774 of 894 HNC radiation patients were ever prescribed opioids. Relative to the start of radiation, the numbers of HNC radiation patients prescribed opioids were: 259 (29%) within < 30 days prior; 355 (40%) within 30 days after; 329 (37%) within 30-60 days after; 142 (16%) within 60-90 days after; 86 (10%) within 90-120 after; 67 (7%) within 120-150 days after; 56 (6%) within 150-180 days after; 53 (6%) within 80-210 days after; 43 (5%) within 210-240 days after. Across all time periods for HNC radiation patients fentanyl (72-83%) and oxycodone (79-85%) were the most common opioid prescriptions, while morphine (14-24%) and hydromorphone (22-27%) were the least common opioid prescriptions. Concurrent gabapentin prescriptions were given to > 80% of HNC patients with opioid prescriptions at every time period, peaking at 91% at the end of radiation. Compared to BC radiation patients, HNC radiation patients had an odds ratio of 3.34 (95% CI: 1.79-6.80, p = < 0.01) in favor of opioid prescriptions and 8.26 (95% CI: 5.74-12.15, p = < 0.01) for adjunctive medicine prescriptions. There was no significant difference between prescriptions by age, race, ethnicity, or prior smoking history. Males compared to females had a lower odds ratio of 0.37 (p = < 0.01) for opioid prescriptions. Conclusions: HNC radiation patients have high rates of opioid and adjunctive medicine prescriptions at our center. Opioids are most prescribed before and during radiation and decrease by > 80% by 6 months after radiation started. 6% of HNC patients still require opioid prescriptions over 6 months after the start of radiation. HNC radiation patients use opioids and adjunctive medicines much more frequently than BC radiation patients.

Real-world use, dose intensity, and adherence to enfortumab vedotin (EV) in locally advanced or metastatic urothelial cancer (la/mUC).

e16567 Background: EV, the first antibody drug conjugate approved for la/mUC, received accelerated approval in the US in 2019 as later-line therapy (post-immunotherapy and platinum-chemotherapy) and regular approval in 2021 with label expansion to include earlier-line therapy (cisplatin-ineligible, ≥1 prior therapy). Because EV delivery per current labelling (1.25 mg/kg, D1, 8, 15 of a 28D cycle) may differ from routine practice, we examined real-world EV use, dose intensity and adherence across 280 US cancer clinics. Methods: This descriptive post-marketing retrospective cohort study used the Flatiron Health longitudinal database derived from EHR records of US patients with la/mUC initiating EV on or after December 19, 2019. We summarized EV use, including but not limited to: % cisplatin-ineligible, and median duration of use and number of cycles administered. We computed metrics of dose intensity: average treatment rate (mean number of treatments per patient-month), dosing frequency (mean number of treatments per cycle), dose (mean dose, mg/kg), and % change in dose (mg) from baseline (difference in dose between last recorded treatment in last cycle and first recorded treatment in first cycle). Finally, we measured treatment adherence, defined as % of cycles across all patients where a patient had > 2 treatments per 28D cycle. Results: Among patients with la/mUC, we identified 416 EV users (mean [SD] age 71 [9] years, 27.4% female, 24.8% non-white, 70.2% prior smokers, 17.5% ECOG 2+, 81.5% from community sites). EV use, dose intensity, and adherence are shown (table). Most were cisplatin-ineligible (55%). Average dosing frequency (2.4 [0.5] treatments per cycle) and dose (1.1 [0.2] mg/kg) were lower than label indication guidelines; 58.8% received > 2 treatments per 28D cycle. Conclusions: Among la/mUC patients treated with EV in contemporary practice, treatment frequency and dosing were lower than recommended in the product labelling. Further research is required to understand clinical factors and outcomes associated with the differences observed. [Table: see text]

Change in Smoking Behavior and Outcome After Ischemic Stroke: Post-Hoc Analysis of the SPS3 Trial.

Cigarette smoking is a known risk factor for cardiovascular disease, including ischemic stroke. The literature regarding the rate of persistent smoking after acute ischemic stroke and its effect on subsequent cardiovascular events is scarce. With this study, we aimed to report the rate of persistent smoking after ischemic stroke and the association between smoking status and major cardiovascular outcomes. This is a post-hoc analysis of the SPS3 trial (Secondary Prevention of Small Subcortical Strokes). Patients were divided into 4 groups based on smoking status at trial enrollment: (1) never smokers, (2) former smokers, (3) smokers who quit at 3 months, and (4) persistent smokers. The primary outcome is a major adverse cardiovascular events composite of stroke (ischemic and hemorrhagic), myocardial infarction, and mortality. Outcomes were adjudicated after month 3 of enrollment until an outcome event or the end of study follow-up. A total of 2874 patients were included in the study. Of the total cohort, 570 patients (20%) were smokers at enrollment, of whom 408 (71.5%) patients continued to smoke and 162 (28.4%) quit smoking by 3 months. The major adverse cardiovascular events outcome occurred in 18.4%, 12.4%, 16.2%, and 14.4%, respectively, in persistent smokers, smokers who quit, prior smokers, and never smokers. In a model adjusted for age, sex, race, ethnicity, education, employment status, history of hypertension, diabetes, hyperlipidemia, myocardial infarction, and intensive blood pressure randomization arm, the risk of major adverse cardiovascular events, and death were higher in the persistent smokers compared with never smokers (HR for major adverse cardiovascular events: 1.56 [95% CI, 1.16-2.09]; HR for death: 2.0 [95% CI, 2.18-3.12]). The risk of stroke, and MI did not differ according to smoking status Conclusions: Compared with never smoking, persistent smoking after acute ischemic stroke was associated with an increased risk of cardiovascular events and death. URL: https://www. gov; Unique identifier: NCT00059306.

847 CONCENTRATIONS OF GROWTH DIFFERENTIATION FACTOR 15 AND LEFT VENTRICULAR FUNCTION IN SURVIVORS FROM HODGKIN LYMPHOMA TREATED WITH ANTHRACYCLINE-CONTAINING CHEMOTHERAPY

Abstract Background Recent studies have shown that the concentrations of growth differentiation factor 15 (GDF-15) increase after anthracycline administration and may be associated with cardiotoxicity during or shortly after treatment. The relation of GDF-15 with late-onset cardiotoxicity has far less been studied. Methods We examined GDF-15 levels across the spectrum of left ventricular (LV) function in a single-center cohort of adult patients who had received curative chemotherapy for Hodgkin lymphoma and underwent comprehensive cardiologic assessment including transthoracic echocardiography (TTE) as part of long-term follow-up. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay, and the concentrations between TTE phenotypes were compared by unpaired Student's t test. The correlation between GDF-15 values and echocardiographic parameters was investigated by linear regression. Results 35 (18 males, 51%) patients were evaluated a median of 47 months (IQR 24-67) after doxorubicin-containing chemotherapy. The median age at the end of treatment and at the time of TTE was 35 years (IQR 28-50) and 40 years (IQR 32-56), respectively. All subjects had received ABVD with or without rituximab as a first-line treatment; 2 (6%) had also received mediastinal irradiation, 6 (17.4%) a second-line therapy, 2 (8.7%) a third-line treatment, and 8 (17.4%) had ultimately undergone bone marrow transplantation. None had a history of heart disease or atrial fibrillation, nor NYHA class ≥II. Body mass index was 24 ± 5 Kg/m2. Seven (20%) patients had hypertension, 9 dyslipidemia (26%), and 2 (6%) diabetes; 28 (80%) were prior or current smoker. Mean GDF-15 was 1132,9 ± 485,0 pg/mL. LV ejection fraction (LVEF) was always >50%; 3 (9%) subjects had global longitudinal strain (GLS) < -18%. Moreover, 7 (20%) had mild or moderate diastolic dysfunction, as defined by E/A ratio <1 or a pseudonormal mitral inflow pattern, respectively. There was no significant relation between GDF-15 and LVEF or GLS values. By contrast, GDF-15 levels were higher in patients with diastolic dysfunction than in those without. Moreover, GDF-15 concentrations correlated with E/A and E/e’ ratios, estimated pulmonary capillary wedge pressure, and estimated systolic pulmonary artery pressure (Figure). Conclusions Our results suggest that GDF-15 tracks with LV diastolic, rather than systolic, dysfunction years after anthracycline chemotherapy.

Abstract 13351: Firefighter Coronary Atherosclerotic Burden Compared to Non-Firefighters

Introduction: Cardiovascular (CV) disease is the leading cause of death for on-duty firefighters. According to the National Fire Protection Association (NFPA), 44% of all fatalities were due to sudden cardiac deaths, and 90% of which were due to coronary artery disease. Furthermore, firefighters are prone to occupational behaviors, conditions, and environmental exposures that may increase their adverse outcomes. In this study, we will attempt to explore the atherosclerotic differences between firefighters and non-firefighter individuals. Methods: 302 firefighters from the Los Angeles fire department who underwent coronary computed tomography angiogram from 2008 to 2021 were matched 1:1 for age, gender, race, diabetes mellitus (DM), hyperlipidemia (HLD), hypertension (HTN), and past smoking to a control cohort for comparison of semi-quantitative coronary plaque burden. Each coronary segment was assessed by a semi-quantify plaque severity (0 for no plaque, 1 for minimal or mild, 2 for moderate, 3 for severe) and luminal stenosis (0: none, 1: <30%, 2: 30-49%, 3: 50-69%, 4: 70-99% and 5:100%). The total plaque severity score (TPS) was calculated by the sum of the individual segment plaque severity score. The total segment stenosis score (TSS) was calculated by adding all the individual segment stenosis score (SSS). Segment involvement score (SIS) was calculated by summing the total number of coronary segments with plaque. Results: Mean (SD) age was 51.3 (6.6); 2% were diabetic; 34% had hyperlipidemia; 19% were hypertensive; 10% were prior smokers in each cohort. The Fire Fighter cohort had significantly higher coronary calcium scores (mean 42.5 vs 12); p<0.0001, TPS at 3 (IQR (1,6) vs 2 (IQR (0,5)); p<0.0001, TSS 3 (IQR (1,5) vs 2 (IQR (0,5)); p<0.0001 , and SIS 2 (IQR (1,4) vs 2 (IQR (0,4)); p<0.0001. Conclusions: After matching for age, gender, race, DM, HTN, HLD, and past smoking. Firefighters had more plaque burden, more stenosis, and more diffuse disease when compared to nonfirefighters, illustrating the occupational effects on the atherosclerotic process

Subsidence after lateral lumbar interbody fusion using a 3D-printed porous titanium interbody cage: single-institution case series.

Cage subsidence is a well-known phenomenon after lateral lumbar interbody fusion (LLIF), occurring in 10%-20% of cases. A 3D-printed porous titanium (pTi) cage has a stiffness that mimics the modulus of elasticity of native vertebrae, which reduces stress at the bone-hardware interface, lowering the risk of subsidence. In this study, the authors evaluated their institutional rate of subsidence and resultant reoperation in patients who underwent LLIF using a 3D-printed pTi interbody cage. This is a retrospective case series of consecutive adult patients who underwent LLIF using pTi cages from 2018 to 2020. Demographic and clinical characteristics including age, sex, bone mineral density, smoking status, diabetes, steroid use, number of fusion levels, posterior instrumentation, and graft size were collected. The Marchi subsidence grade was determined at the time of last follow-up. Outcome measures of interest were subsidence and resultant reoperation. Univariable logistic regression analysis was performed to assess the extent to which clinical and operative characteristics were associated with Marchi grade I-III subsidence. Significance was assessed at p < 0.05. Fifty-five patients (38 with degenerative disc disease and 17 with adult spinal deformity) were treated with 97 pTi interbody cages with a mean follow-up of 18 months. The mean age was 63.6 ± 10.1 years, 60% of patients were female, and 36% of patients had osteopenia or osteoporosis. Patients most commonly underwent single-level LLIF (58.2%). Sixteen patients (29.1%) had posterior instrumentation. The subsidence grade distribution was as follows: 89 (92%) grade 0, 5 (5%) grade I, 2 (2%) grade II, and 1 (1%) grade III. No patients who were active or prior smokers and no patients with posterior instrumentation experienced graft subsidence. No clinical or operative characteristics were significantly associated with graft subsidence. One patient (1.8%) required reoperation because of subsidence. In this institutional case series, subsidence of pTi intervertebral cages after LLIF occurred in 8% of operated levels, 3% of which were grade II or III. Only 1 patient required reoperation. These reported rates are lower than those reported for polyetheretherketone implants. Further studies are necessary to compare the impact of these cage materials on subsidence after LLIF.

Personalized circulating tumor DNA (ctDNA) analysis in patients with recurrent/metastatic head and neck squamous cell cancer (R/M HNSCC).

6052 Background: Immuno-oncology agents (IO) have become standard-of-care in the treatment of R/M HNSCC, but only a subset of patients (pts) benefit. Highly sensitive quantification of plasma circulating tumor DNA (ctDNA) may permit real time assessment of disease under selective pressures of treatment. Methods: R/M HNSCC pts treated with platinum-based chemotherapy (CT) or IO (anti-PD1/L1 +/- second IO) underwent serial ctDNA collection pre-cycles 1/2/3 and at disease progression, corresponding to timepoints (T) 1-4. T1 was considered baseline. Whole exome sequencing of pt tumor tissue identified patient specific somatic variants which were used as targets for RaDaR, a personalized multiplexed PCR-based NGS assay. Matched buffy coat DNA was sequenced to filter germline mutations and identify confounding CHIP. RaDaR was applied at each available T, an estimated variant allele frequency (eVAF) was calculated and correlated with progression free- (PFS) and overall- survival (OS). Findings were compared against prior (ESMO 2021) data generated using a fixed 580 gene CAPP-seq (CAncer Personalized Profiling by deep Sequencing) panel designed specifically against squamous cell carcinoma. Results: A total 114 plasma samples from 38 pts were analyzed. Of 35 pts with ctDNA detected at T1 and/or T2, 26 received IO and 9 CT. Median age was 62 (20-84), 77% were male, 69% prior smokers and 26% HPV positive. Median PFS and OS, for all 35 pts, was 2.57 mo (95% CI 0.48-4.66) and 8.37 mo (95% CI 5.42-11.32) respectively. For IO treated pts, median PFS was 2.45 mo (95% CI 0-5.18) and median OS 7.38 mo (95% CI 3.84-10.93). RaDaR panels targeted a median 48 variants (17-50). ctDNA was detected in 35/38 (92%) patients at baseline, with median eVAF 0.345% (range 0.0004% - 43.37%). ctDNA abundance at baseline did not correlate with PFS or OS. A decrease in Δ eVAF from T1 to T2, by &gt; 30%, or &gt; 50% identified pts with improved PFS, with HR 0.45 (0.21, 0.96) p = 0.04, 0.31 (0.14, 0.70) p &lt; 0.01, and 0.23 (0.10, 0.56) p &lt; 0.01, respectively. Similar results were observed for the 26 IO pts, with HR 0.40 (0.16, 1.03) p = 0.06, 0.19 (0.05, 0.66) p &lt; 0.01, and 0.06 (0.01, 0.47) p &lt; 0.01, respectively. A similar, but non-significant, trend was seen in median OS for pts with a decrease vs. increase in Δ eVAF (T1 to 2), 8.8 mo vs 7.3 mo (HR = 0.87 (0.42, 1.79)). For 31 pts, a comparison of Δ ctDNA levels, based on personalized RaDaR vs. CAPP-seq assays, from T1 to T2 demonstrated a correlation coefficient of R = 0.57, P &lt; 0.01. Conclusions: In pts with R/M HNSCC, a decrease in ctDNA eVAF after first treatment correlated with improved PFS. There was a significant correlation between fixed CAPP-seq and personalized RaDaR assays when comparing Δ in ctDNA levels. Clinical Trial: NCT03712566.

A novel approach to assessing the effects of smoking on treatment response rate in muscle-invasive bladder cancer.

e16554 Background: Cigarette smoking is the strongest modifiable risk factor for bladder cancer and has been implicated in mechanisms of chemotherapy resistance. Prior studies examining tobacco exposure on chemotherapy response were limited by use of retrospective design and self-report assessment of smoking status, potentially under-estimating the association and risking bias towards the null. Cotinine is the central metabolite of nicotine and can be detected in saliva for up to 4 days after tobacco use. In this prospective cohort study, we tested the association between salivary cotinine level and pathologic response to neoadjuvant chemotherapy, assessed post-chemotherapy at the time of cystectomy, among patients with muscle-invasive bladder cancer (MIBC). Methods: Thirty-one patients with MIBC were prospectively recruited and surveyed on their smoking habits. Salivary cotinine was measured during chemotherapy using NicAlert test strips with cotinine concentration &gt; 10ng/mL indicating active smoking (cotinine = 1) and cotinine concentration &lt; 10ng/mL indicating no evidence of active tobacco use (cotinine = 0). Primary outcome was pathologic response at cystectomy, defined as complete response (pT0) or residual disease (pT1-4 or node+). For patients with prior history of tobacco use, the association between pre-chemotherapy cotinine level and post-chemotherapy response at cystectomy was assessed using a chi-squared test and an odds ratio with a 95% confidence interval (CI) using the Baptista-Pike method. Results: Thirty-one patients had cotinine levels measured during chemotherapy and 25 reported prior history of smoking. Of these 25 patients, 17 patients denied active smoking, 2 of whom had cotinine levels = 1 during chemotherapy. Response to chemotherapy by cotinine level among patients with prior history of tobacco use are shown in table 1. One patient declined cystectomy and was excluded from the analysis. The odds ratio of a complete response at cystectomy for patients with cotinine = 0 vs. cotinine = 1 was 3.86 (95% CI: 0.54-22.05) (p = 0.148). The odds ratio of residual disease with cotinine = 0 vs. cotinine = 1 was 0.26 (95% CI: 0.045-1.86) (p = 0.148). Conclusions: Prior smokers with no evidence of active tobacco use during curative chemotherapy were more than three-times as likely to demonstrate a complete response at the time of cystectomy compared to those with evidence of current tobacco use based on salivary cotinine levels. While this study was limited by a small sample size, it highlights a novel approach to tobacco use monitoring and the importance of continued smoking cessation counseling in patients with bladder cancer even after the diagnosis of cancer is made.[Table: see text]

Landscape of KRASG12C, Associated Genomic Alterations, and Interrelation With Immuno-Oncology Biomarkers in KRAS-Mutated Cancers.

PURPOSEPromising single-agent activity from sotorasib and adagrasib in KRASG12C-mutant tumors has provided clinical evidence of effective KRAS signaling inhibition. However, comprehensive analysis of KRAS-variant prevalence, genomic alterations, and the relationship between KRAS and immuno-oncology biomarkers is lacking.MATERIALS AND METHODSRetrospective analysis of deidentified records from 79,004 patients with various cancers who underwent next-generation sequencing was performed. Fisher's exact test evaluated the association between cancer subtypes and KRAS variants. Logistic regression assessed KRASG12C comutations with other oncogenes and the association between KRAS variants and immuno-oncology biomarkers.RESULTSOf the 79,004 samples assessed, 13,758 (17.4%) harbored KRAS mutations, with 1,632 (11.9%) harboring KRASG12C and 12,126 (88.1%) harboring other KRAS variants (KRASnon-G12C). Compared with KRASnon-G12C across all tumor subtypes, KRASG12C was more prevalent in females (56% v 51%, false discovery rate-adjusted P value [FDR-P] = .0006), current or prior smokers (85% v 56%, FDR-P < .0001), and patients age > 60 years (73% v 63%, FDR-P ≤ .0001). The most frequent KRAS variants across all subtypes were G12D (29.5%), G12V (23.0%), G12C (11.9%), G13D (6.5%), and G12R (6.2%). KRASG12C was most prevalent in patients with non–small-cell lung cancer (9%), appendiceal (3.9%), colorectal (3.2%), tumor of unknown origin (1.6%), small bowel (1.43%), and pancreatic (1.3%) cancers. Compared with KRASnon-G12C-mutated, KRASG12C-mutated tumors were significantly associated with tumor mutational burden-high status (17.9% v 8.4%, odds ratio [OR] = 2.38; FDR-P < .0001). KRASG12C-mutated tumors exhibited a distinct comutation profile from KRASnon-G12C-mutated tumors, including higher comutations of STK11 (20.59% v 5.95%, OR = 4.10; FDR-P < .01) and KEAP1 (15.38% v 4.61%, OR = 3.76; FDR-P < .01).CONCLUSIONThis study presents the first large-scale, pan-cancer genomic characterization of KRASG12C. The KRASG12C mutation was more prevalent in females and older patients and appeared to be associated with smoking status. KRASG12C tumors exhibited a distinct comutation profile and were associated with tumor mutational burden-high status.

Chemoradiation with Hypofractionated Proton Therapy in Stage II-III Non-Small Cell Lung Cancer: A Proton Collaborative Group Phase 2 Trial

Hypofractionated radiation therapy has been safely implemented in the treatment of early-stage non-small cell lung cancer (NSCLC) but not locally advanced NSCLC owing to prohibitive toxicities with photon therapy. Proton therapy, however, may allow for safe delivery of hypofractionated radiation therapy. We sought to determine whether hypofractionated proton therapy with concurrent chemotherapy improves overall survival. The Proton Collaborative Group conducted a phase 1/2 single-arm nonrandomized prospective multicenter trial from 2013 through 2018. We received consent from 32 patients, of whom 28 were eligible for on-study treatment. Patients had stage II or III unresectable NSCLC (based on the 7th edition of the American Joint Committee on Cancer's staging manual) and received hypofractionated proton therapy at 2.5 to 4 Gy per fraction to a total 60 Gy with concurrent platin-based doublet chemotherapy. The primary outcome was 1-year overall survival comparable to the 62% reported for the Radiation Therapy Oncology Group (RTOG) 9410 trial. The trial closed early owing to slow accrual, in part, from a competing trial, RTOG 1308. Median patient age was 70 years (range, 50-86 years). Patients were predominantly male (n=20), White (n=23), and prior smokers (n=27). Most had stage III NSCLC (n=22), 50% of whom had adenocarcinoma. After a median follow-up of 31 months, the 1- and 3-year overall survival rates were 89% and 49%, respectively, and progression-free survival rates were 58% and 32%, respectively. No acute grade ≥3 esophagitis occurred. Only 14% developed a grade ≥3 radiation-related pulmonary toxic effect. Hypofractionated proton therapy delivered at 2.5 to 3.53 Gy per fraction to a total 60 Gy with concurrent chemotherapy provides promising survival, and additional examination through larger studies may be warranted.

458 Pulsed Electromagnetic Fields (PEMF) Used in Cervical Spine Fusion for Patients with Risk Factors for Non-Union

INTRODUCTION: A post market prospective study was conducted to examine the effect of the adjunctive use of a pulsed electromagnetic field (PEMF) device on cervical fusion rate in subjects with risk factors for non-union. PEMF has been shown to stimulate bone healing and can be a valuable tool to help overcome biological deficiencies in patients at risk for non-union. METHODS: Patients undergoing cervical fusion surgery were identified for enrollment from 11 investigator sites based on being classified as having one or more risk factors for non-union. Subjects were those having a multi-level (2 or more) fusion, prior cervical spine fusion, diabetes, osteoporosis, or smokers. Subjects were required to wear the PEMF device for 4 hours/day for 6 months. Compliance was measured based on usage data downloaded from the device. The primary outcome measure was fusion status at 12 month follow-up period as indicated by x-ray and CT. Fusion status was determined by the site investigator using A/P, lateral, and flexion/extension radiographs in addition to CT (without contrast). RESULTS: Out of 152 subjects, 138 (90.8%) were graded as fused (all levels) at the 12 month visit About half of the subjects (49.3%) had 3 or more levels fused. Fusion success for subjects with 2 or more risk factors was 88.5%, and was 94.4% for subjects with a single risk factor. On average, compliance rates (minutes using device/minutes prescribed) were 83.8% and 74.9% for the 3 and 6 month visit, respectively. The followup rate at the 12 month visit was 97%. CONCLUSION: The results of our study suggest that adjunctive use of PEMF is effective in cervical spine fusion patients with factors associated with non-union. Favorable fusion rates were obtained with patients having elevated comorbidity and/or complex surgeries. Further research is planned to include a control group in a real world setting to better assess the impact of the PEMF device in this population.

Postoperative decline in ambulatory function after lower extremity bypass is associated with higher short- and long-term mortality

ObjectiveAlthough the importance of preexisting functional and ambulatory status among patients undergoing lower extremity bypass (LEB) has been increasingly recognized, a paucity of reported data is available on the significance of a postoperative decline in ambulatory status after LEB surgery. The purpose of the present analysis was to determine the effects of a new decline in ambulatory status after LEB surgery on the postoperative short- and long-term outcomes. MethodsThe Vascular Quality Initiative infrainguinal bypass dataset was queried from 2003 to 2021 for patients with peripheral arterial disease (PAD) who had undergone LEB. Information on ambulatory status at admission and discharge from the hospital was recorded. Patients with a decline in ambulatory status at discharge from the hospital were included in group I, and those who had maintained their ambulatory status at discharge were included in group II. The primary outcomes were mortality, amputation, and a composite outcome of mortality or amputation at 30 days and 1 year postoperatively. The secondary outcomes were major adverse cardiovascular events, myocardial infarction, congestive heart failure, stroke, dysrhythmia, pneumonia, and the need for prolonged ventilation. ResultsA total of 40,478 patients were included in the present study, of whom 16,032 (39.6%) were included in group I and 24,446 (60.4%) were included in group II. The patients in group I were more often aged >70 years, women, African American, transferred from another hospital or rehabilitation facility, prior or current smokers, or had an American Society of Anesthesiologists classification of III or IV compared with those with unchanged ambulatory status (P < .05 for all). Patients with a decline in ambulatory status had had a greater incidence of mortality at 30 days (2.4% vs 0.6%; P < .001) and 1 year (9.7% vs 7%; P < .001) postoperatively. Patients with a decline in ambulatory status had had a greater occurrence of major adverse cardiovascular events, myocardial infarction, stroke, dysrhythmia, and the need for prolonged ventilation. The following factors were associated with a decline in postoperative ambulatory status: older age (70-79 years: adjusted odds ratio [aOR], 1.20; 95% confidence interval [CI], 1.07-1.34; P = .001; and ≥80 years: aOR, 1.18; 95% CI, 1.05-1.35; P = .007), female sex (aOR, 1.06; 95% CI, 1.00-1.11; P = .019), African-American race (aOR, 1.15; 95% CI, 1.07-1.21; P < .001), transfer from another hospital or rehabilitation unit (aOR, 1.30; 95% CI, 1.18-1.41; P < .001), and a history of diabetes mellitus (aOR, 1.12; 95% CI, 1.06-1.17; P = .004). The magnitude of decline in ambulatory function was associated with worse primary outcomes. Patients whose ambulatory function had declined from ambulatory to bedridden after LEB surgery had had the highest mortality (aOR, 21 at 30 days and 15 at 1 year). ConclusionsA new decline in ambulatory function at discharge from the hospital after LEB surgery was associated with increased short- and long-term mortality and the composite outcome of mortality or amputation. It was also associated with reduced amputation-free survival at 30 days and 1 year postoperatively.