Citations

Acquired tracheoesophageal fistula (TEF) is a rare complication of esophageal or lung cancer. A 57-year-old male presented with complaints of vomiting, cough, 20 lb weight loss, and progressive dysphagia. Early laryngoscopy and CT chest showed a normal pharynx with an irregular thickness of the thoracic esophagus. The upper gastrointestinal endoscopy (UGIE) and upper endoscopic ultrasound (EUS) revealed a hypoechoic mass evolving as complete obstruction. During the procedure, minimal CO2 was used for insufflation; however, when attempts were made to traverse the obstruction, capnography revealed an end-tidal CO2 (EtCO2) estimating 90 mmHg indicating possible TEF. This case depicts the use of capnography during UGIE in diagnosing an acquired TEF.

AbstractNeuromodulation in epilepsy is a proven treatment for people with drug‐resistant focal epilepsy. Dual device therapies are increasingly utilized in people with drug‐resistant epilepsy. Vagus nerve stimulation (VNS) and deep brain stimulation (DBS) target the thalamus involving the primary neurobiological network in patients with genetic generalized epilepsy (GGE). We report a novel case of combined neuromodulation in a patient with drug‐resistant GGE who achieved a partial response with seizure reduction after VNS implantation yet following VNS‐DBS polyneurostimulation gradually achieved prolonged seizure freedom. We speculate that by combining the indirect activating effects of VNS with the direct inhibitory effects of DBS, this may provide synergy to thalamic modulated networks. We hypothesize a “rational polytherapy” may exist in some patients with GGE undergoing dual neuromodulation.

695 Background: Recent results from COSMIC 313 trial and updated findings from other contemporary trials have added to the existing body of evidence for 1L mRCC. Therefore, we present the most up-to-date results from our living, interactive systematic review (LISR) to facilitate the choice of optimal therapy in 1L mRCC setting. Methods: This LISR and network meta-analysis is maintained using a novel living evidence synthesis (LIvE) framework. The framework facilitates the identification of new or updated studies using an automated ‘living’ search which is followed by screening and extraction in a semi-automated fashion within a machine learning assisted graphical user interface. Relevant data is parsed and analyzed to compute mixed treatment comparisons and certainty of evidence is adjudicated using a rule-based algorithm. Detailed methods have been published before (PMID: 33824031). Results: As of October 1st 2022, this LISR includes 16 clinical trials (30 references). Mixed treatment comparisons showed statistically significant PFS benefit with lenvatinib-pembrolizumab (LenPem; rank 1) when compared to cabozantinib-nivolumab (CabNivo; rank 3; hazard ratio [HR]: 0.69, 95% confidence interval: 0.52-0.93), CaboNivo-ipilimumab (CaboNivoIpi; rank 4; HR: 0.62; 0.43-0.89), avelumab-axitinib (AveAxi; rank 5; HR: 0.56; 0.43-0.75), PemAxi (rank 6; HR: 0.55; 0.42-0.72), atezolizumab-bevacizumab (AteBev; rank 7; HR: 0.46; 0.35-0.59), and NivoIpi (rank 8; HR: 0.45; 0.35-0.59). No significant differences were observed between CaboNivoIpi and other combination therapies for PFS improvement. Similarly, for OS, LenPem (rank 1), PemAxi (rank 2) and CaboNivo (rank 3) were ranked as potentially more efficacious treatment options than other counterparts. However, no statistically significant difference was observed for OS benefit with mixed treatment comparisons. The odds of achieving an ORR were higher with LenPem (rank 1; odds ratio [OR]: 2.44; 1.43-4.17), and CaboNivo (rank 2; OR: 1.77; 1.04-3.03) when compared to CaboNivoIpi (rank 6). NivoIpi (rank 1), LenPem (rank 2), CaboNivoIpi (rank 3) were ranked potentially as more efficacious treatments for achieving a CR. In terms of grade 3 or higher treatment related adverse events, NivoIpi (rank 3) was ranked as potentially the safest option among other combinations while CaboNivoIpi (rank 12), LenPem (rank 11), and CaboNivo (rank 10) were more likely to increase the risk of toxicity compared to most other treatments. Conclusions: Triplet combination of CaboNivoIpi may not provide additional survival benefit compared to other immunotherapy combinations and may increase toxicity. Patient-level considerations such as treatment toxicity, and quality of life should be factored in when opting intensified 1L therapies in mRCC patients.

116 Background: The impact of socioeconomic status on genitourinary (GU) cancer mortality in the United States (US) is unclear. Hence, we evaluated the association of the socioeconomic status with GU cancer mortality across the US counties. Methods: County-level age-adjusted mortality rates (AAMR) per 100,000 person-years (PY) for populations diagnosed with GU cancers were abstracted from the wide-ranging online data for epidemiological research (WONDER) database. The agency for toxic substances and disease registry (ATSDR) was queried to obtain county-level social vulnerability indices from 2014-2018. Percentile ranking scores (PRS: ranging from 0-1) were computed for each US county and further categorized into quartiles (Q: 1st: 0-0.25 [least vulnerable]; 4th: 0.75-1.00 [most vulnerable]). AAMRs were then linked with quartile rankings. A population-weighted, Poisson regression analysis was conducted to compute rate ratios (RR) of AAMRs between 4th and 1st Q with the corresponding 95% confidence intervals (CI). Results: A total 3142 US counties were included in this analysis. The AAMR for GU cancers was 22.6 overall deaths (OD) and 4.20 premature deaths (PD; defined as death at age <65 years) per 100,000 PY. GU cancer-related mortality increased in a stepwise fashion from the 1st Q to the 4th Q (OD: 21.6 vs 24.1; PD: 3.48 vs 5.19). In terms of OD by specific GU cancers, significantly higher AAMRs were observed in the 4th Q compared to the 1st Q for patients with prostate cancer (RR; 1.19 [95% CI;1.14-1.24]), and renal cell carcinoma (RCC; 1.12 [1.04-1.21]) but not for those with lower urothelial tract cancers (0.92 [0.87-0.96]). Among subgroups, non-Hispanic Blacks (1.19 [1.07-1.33]), and Hispanics (1.28 [1.08-1.51]) with prostate cancer and men with RCC (1.11; 1.03-1.19) in the 4th Q experienced significantly higher overall mortality when compared to those in the 1st Q. With regards to PD, significantly higher AAMRs were observed in the 4th Q vs 1st Q for patients with prostate cancer (1.54 [1.34-1.77]), and RCC (1.28 [1.12-1.45]). Consistently, men with RCC in the 4th Q also experienced higher premature mortality when compared to the 1st Q. Sparsity of mortality data among different ethnic/racial subgroups across the US counties precluded any formal assessment of disparity by specific GU cancers. A sensitivity analysis, conducted using the weighted linear regression approach, showed consistent results. Conclusions: Population level data suggest that socially vulnerable populations, especially Non-Hispanic Black and Hispanic men with prostate cancer, and men with renal cell carcinoma may be at an increased risk of cancer-related mortality. Hence, there is a dire need to address this mortality gap across different socioeconomic subgroups to ensure health-care equity. Investigations at the patient level are required to further ascertain these findings.

A 35-year-old male greenhouse worker presented with myalgia, fatigue, and fever. Initially, he was thought to have an unspecified viral infection and was treated with conservative therapy. However, the patient’s symptoms persisted, and he reported additional symptoms of mild abdominal pain and headaches. Laboratory evaluation was significant for elevated liver enzymes. Due to concern for acute hepatitis and persistent fever the patient was hospitalized. During his hospital course, no infectious etiology was found to explain his symptoms. After discharge from the hospital, additional testing showed positive serology for Q fever IgG phase II antibody (1:8192) and phase II antibody IgM (> 1:2048). He was treated with doxycycline and had a good clinical response. Upon follow-up, he had worsening Phase I IgG serologies. Transesophageal echo demonstrated vegetations consistent with endocarditis.

Abstract Background: Adjuvant oral tamoxifen (TAM) benefits women with DCIS, but toxicity concerns have limited its acceptance. Transdermal therapy with 4-hydroxy tamoxifen (4-OHT) gel applied to the breast skin is a possible solution. Previous pilot data suggest equivalent anti-proliferative efficacy of TAM and 4-OHT gel, but minimal systemic exposure with transdermal therapy. We report a prospective double blinded randomized phase 2 trial comparing TAM to 4-OHT gel in women with DCIS. Methods: 107 women with estrogen receptor positive (≥10%) DCIS were randomized to TAM (20 mg/day + placebo gel) or 4-OHT gel (2mg 4-OHT gel/breast, bilaterally + oral placebo), for 4-10 weeks prior to surgery. The primary endpoint was reduction in DCIS Ki67 labeling index (LI). Secondary endpoints included the 12-gene DCIS Score assay (Exact Sciences), breast tissue and plasma concentrations of 4-OHT and endoxifen, TAM-responsive circulating proteins, and patient reported symptoms (Breast Eight Symptom Scale). We estimated that 80 evaluable participants would provide 80.5% power to establish non-inferiority of 4-OHT, defined as relative Ki67-LI decline &gt;35% and absolute decline &gt;2.6%, with one-sided 𝛼=0.10. Non-inferiority of 4-OHT gel for Ki67-LI reduction was tested using an ANCOVA model. Statistical comparisons within- and between-arms were calculated with paired t-test and Welch Two Sample t-test, respectively. Results: 72 of 87 women adhered to the protocol, and were evaluable for the primary endpoint (39 TAM and 33 4-OHT gel). Mean treatment duration was 47 days for TAM and 44 days for 4-OHT gel (p=0.2). The median absolute decline in Ki67 labeling index was significant in the oral TAM (-3.7%, p&lt; 0.001) but not in 4-OHT gel arm (-1.3%, p=0.2) (p=0.002). Ki67 results following menopausal stratification also favored the TAM arm: (-1.3%; p=0.06 in 37 premenopausal women and -3.7%; p=0.02 in 35 postmenopausal women). Similarly, DCIS score showed a significantly greater reduction in the TAM (-14, p&lt; 0.001) but not in the 4-OHT gel arm (-4, p=0.1). Tissue 4-OHT concentrations were non-significantly higher in the TAM arm and were similar between superficial and deep sampling locations (superficial 6.1 and 4.2 ng/g for TAM and 4-OHT gel, respectively, p= 0.55; deep 5.7 and 3.8 ng/g, respectively, p= 0.06), whereas plasma 4-OHT concentration was markedly lower in the gel group (2 ng/mL and 0.24 ng/mL for TAM and 4-OHT gel, respectively, P &lt; 0.001). Endoxifen was abundant in plasma (11 ng/mL) and deep tissue (13 ng/g) of the TAM arm, but present in trace amounts in the 4-OHT gel arm (undetectable in plasma and 0.31 ng/g in tissue; p &lt; 0.001). Circulating TAM responsive markers (insulin like growth factor 1, sex hormone binding globulin, von Willebrand factor, and protein S total) and vasomotor symptoms were significantly and unfavorably modulated by TAM, but not by 4-OHT gel therapy. Conclusions: The non-inferiority of transdermal 4-OHT gel to Tam in terms of anti-proliferative effect in DCIS lesions was not demonstrated at the doses used for this study. DCIS Score analysis gave similar results. Tissue 4-OHT concentration in 4-OHT gel and Tam-treated subjects was roughly similar. However, endoxifen exposure was higher with oral TAM therapy and may partially explain the observed differences in major endpoints. In future studies, use of higher 4-OHT gel doses, longer duration of treatment, or different formulation may overcome these. Citation Format: Oukseub Lee, Xinlei Mi, Yanfei Xu, Luis Blanco, Azza M. Akasha, Kelly Benante, Shanshan Zhang, Carissa LaBoy, Thomas Helland, Melissa Pilewskie, Amy Degnim, Zahraa Al-Hilli, Amanda L. Amin, E Shelley Hwang, Joseph M. Guenther, Simon Steinar Hustad, Demirkan B. Gursel, Masha Kocherginsky, Gunnar Mellgren, Eileen Dimond, Marjorie Perloff, Brandy M. Heckman-Stoddard, Seema Khan. PD15-12 A pre-surgical window trial of oral tamoxifen versus transdermal 4-hydroxytamoxifen gel in women with estrogen receptor positive duct carcinoma in situ (DCIS) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD15-12.

Abstract Background: Adjuvant ET has been the standard of care for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) EBC. A significant proportion of patients with increased risk still experience disease relapse despite available ET and more optimum ET is needed to prevent patients developing incurable metastatic cancer. Distant recurrence risk ranges from 20% to 40% after 5 years of adjuvant ET, depending on clinicopathological (clin-path) features at diagnosis. Consequently, there is a need to further optimize adjuvant treatment, particularly in those patients who are at increased risk of recurrence. Imlunestrant is an orally bioavailable selective estrogen receptor degrader (SERD) with pure antagonistic properties and the potential to overcome ET resistance. In early phase trials, imlunestrant monotherapy showed favorable safety with pharmacokinetic (PK) exposures exceeding fulvestrant and preliminary efficacy in ER+, HER2- advanced breast cancer patients (EMBER, Jhaveri 2022) along with robust biological/pharmacodynamic activity and tolerability in EBC (EMBER-2, Neven). Trial Design: EMBER-4 is a randomized, open-label, global phase 3 study comparing imlunestrant versus physicians’ choice of ET, in patients who are at an increased risk of recurrence based on clin-path features and who have received 2 to 5 years of standard adjuvant ET. Approximately 6,000 patients will be randomized 1:1 to receive imlunestrant (400 mg daily) for 5 years or physicians’ choice of adjuvant ET (tamoxifen or an aromatase inhibitor, AI, dosed per label). Study treatment duration is 5 years. Males and pre-/peri-menopausal women will receive concomitant treatment with a GnRH agonist if receiving imlunestrant or an AI. Stratification factors include time from initial adjuvant ET, use of prior adjuvant cyclin dependent kinase 4/6 inhibitors, nodal status, menopausal status, and geographic region. Eligibility criteria: Eligible patients are adult males and females (pre-, peri- or postmenopausal) with ER+, HER2- EBC who have completed definitive locoregional therapy and have received 2 to 5 years of prior adjuvant ET without disease recurrence, but who are at increased risk of recurrence based on clin-path features at diagnosis. Prior (neo) adjuvant chemotherapy and/or targeted therapy with a CDK4/6- or PARP- inhibitor is permitted. Study endpoints: The primary endpoint is invasive disease-free survival (IDFS), excluding second non-breast primary invasive cancers. Key secondary endpoints include distant relapse-free survival, overall survival, IDFS including second non-breast primary invasive cancers, safety, PK and patient reported outcomes. Recruitment for EMBER-4 begins globally in Q4 2022. Citation Format: Komal Jhaveri, Joyce O’Shaughnessy, Fabrice Andre, Matthew P. Goetz, Nadia Harbeck, Miguel Martín, Francois-Clement Bidard, Zachary M. Thomas, Suzanne Young, Roohi Ismail-Khan, Lillian M. Smyth, Michael Gnant. EMBER-4: A phase 3 adjuvant trial of imlunestrant vs standard endocrine therapy (ET) in patients with ER+, HER2- early breast cancer (EBC) with an increased risk of recurrence who have previously received 2 to 5 years of adjuvant ET [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT1-01-02.

Abstract Background and study aims Hemospray (TC-325) is a mineral powder with adsorptive properties designed for use in various gastrointestinal bleeding (GIB) scenarios. We conducted a systematic review & meta-analysis of randomized controlled trials (RCTs) comparing TC-325 to standard endoscopic therapy (SET) for non-variceal GIB (NVGIB). Methods Multiple databases were searched through October 2022. Meta-analysis was performed using a random-effects model to determine pooled relative risk (RR) and proportions with 95 % confidence intervals (CI) for primary hemostasis, hemostasis failure, 30-day rebleeding, length of stay (LOS), and need for rescue interventions. Heterogeneity was assessed using I2%. Results Five RCTs with 362 patients (TC-325 178, SET 184) – 123 females and 239 males with a mean age 65 ± 16 years). The most common etiologies were peptic ulcer disease (48 %), malignancies (35 %), and others (17 %). Bleeding was characterized as Forrest IA (7 %), IB (73 %), IIA (3 %), and IIB (1 %). SET included epinephrine injection, electrocautery, hemoclips, or a combination. No statistical difference in primary hemostasis between TC-325 compared to SET, RR 1.09 (CI 0.95–1.25; I2 43), P = 0.2, including patients with oozing/spurting hemorrhage, RR 1.13 (CI 0.98–1.3; I2 35), P = 0.08. Failure to achieve hemostasis was higher in SET compared to TC-325, RR 0.30 (CI 0.12–0.77, I2 0), P = 0.01, including patients with oozing/spurting hemorrhage, RR 0.24 (CI 0.09 – 0.63, I2 0), P = 0.004. We found no difference between the two interventions in terms of rebleeding, RR 1.13 (CI 0.62–2.07, I2 26), P = 0.8 and LOS, standardized mean difference (SMD) 0.27 (CI, –0.20–0.74; I2 62), P = 0.3. Finally, pooled rate of rescue interventions (angiography) was statistically higher in SET compared to TC-325, RR 0.68 (CI 0.5–0.94; I2 0), P = 0.02. Conclusions Our analysis shows that for acute NV GIB, including oozing/spurting hemorrhage, TC-325 does not result in higher rates of primary hemostasis compared to SET. However, lower rates of failures were seen with TC-325 than SET. In addition, there was no difference in the two modalities when comparing rates of rebleeding and LOS.

Abstract Objective COVID-19 vaccines have a favorable safety profile in patients with autoimmune rheumatic diseases (AIRDs) such as idiopathic inflammatory myopathies (IIMs); however, hesitancy continues to persist among these patients. Therefore, we studied the prevalence, predictors and reasons for hesitancy in patients with IIMs, other AIRDs, non-rheumatic autoimmune diseases (nrAIDs) and healthy controls (HCs), using data from the two international COVID-19 Vaccination in Autoimmune Diseases (COVAD) e-surveys. Methods The first and second COVAD patient self-reported e-surveys were circulated from March to December 2021, and February to June 2022 (ongoing). We collected data on demographics, comorbidities, COVID-19 infection and vaccination history, reasons for hesitancy, and patient reported outcomes. Predictors of hesitancy were analysed using regression models in different groups. Results We analysed data from 18 882 (COVAD-1) and 7666 (COVAD-2) respondents. Reassuringly, hesitancy decreased from 2021 (16.5%) to 2022 (5.1%) (OR: 0.26; 95% CI: 0.24, 0.30, P &lt; 0.001). However, concerns/fear over long-term safety had increased (OR: 3.6; 95% CI: 2.9, 4.6, P &lt; 0.01). We noted with concern greater skepticism over vaccine science among patients with IIMs than AIRDs (OR: 1.8; 95% CI: 1.08, 3.2, P = 0.023) and HCs (OR: 4; 95% CI: 1.9, 8.1, P &lt; 0.001), as well as more long-term safety concerns/fear (IIMs vs AIRDs – OR: 1.9; 95% CI: 1.2, 2.9, P = 0.001; IIMs vs HCs – OR: 5.4 95% CI: 3, 9.6, P &lt; 0.001). Caucasians [OR 4.2 (1.7–10.3)] were likely to be more hesitant, while those with better PROMIS physical health score were less hesitant [OR 0.9 (0.8–0.97)]. Conclusion Vaccine hesitancy has decreased from 2021 to 2022, long-term safety concerns remain among patients with IIMs, particularly in Caucasians and those with poor physical function.