Cervical cancer is the third most common cancer among women worldwide and is usually managed with chemoradiation in advanced disease. This case presents a 41-year-old female with locally advanced cervical cancer who underwent combination intracavitary/interstitial brachytherapy after chemoradiation for local disease control. At her fifth brachytherapy session, one of the interstitial needles was malpositioned and lead to vascular injury with significant blood loss. She subsequently underwent emergent embolization of a branch of the right obturator artery with immediate clinical improvement and no complications. This is the first reported case of vascular injury from an interstitial brachytherapy needle that required arterial embolization for hemostasis.
Vasculitic immune checkpoint inhibitor-related adverse events (irAEs) are rare, with limited data to guide their management. Here, we present a case of a 67-year-old female with stage IV cutaneous melanoma who received first-line pembrolizumab. She had completed 21 cycles of pembrolizumab dosed at 200 mg every 21 days over 15 months when she developed fatigue, chills, decreased appetite, night sweats, nausea, diarrhea, dry cough, and chest pain. A routine, staging positron emission tomography (PET) scan revealed aortitis of the transverse aortic arch. An extensive workup was unremarkable for other causes, so her condition was labeled a grade III immune-related vasculitis. Based on this diagnosis, we started high-dose prednisone and discontinued pembrolizumab. After two months of high-dose prednisone, she developed bothersome weight gain and insomnia, leading to a switch from prednisone to tocilizumab as a steroid-sparing agent. The selection of tocilizumab was based on its routine use for giant cell arteritis which can have extracranial symptoms including thoracic aortitis. Her symptoms resolved, and subsequent PET scans showed resolution of the aortitis and no evidence of metastatic melanoma. As the indications for immunotherapy expand, rare complications are becoming more prevalent, and more data will be needed to guide their management. While there is evidence for tocilizumab use as a steroid-sparing treatment for large-vessel vasculitides due to other conditions, this is the first case of its use to treat an aortitis irAE to our knowledge. In this case, it was an effective means of treating the patient while sparing them from prolonged corticosteroids.
Introduction: Acute myeloid leukemia (AML) has historically been considered an oncologic emergency, requiring immediate intervention and initiation of therapy. Although urgency to initiate treatment has been debated, no guidelines exist to address the impact of diagnosis to treatment interval (DTI) in patients with AML. Recent FDA approvals have added treatment options using targeted therapy as monotherapy in older patients (e.g. - ivosidenib), or in combination with chemotherapy in younger patients (e.g.- midostaurin) in the newly diagnosed setting with improved outcomes. Unfortunately, results of molecular mutation testing often return several days after the initial diagnosis of AML has been made. While immediate induction is important to control disease and to minimize disease-related morbidity and mortality (Sekkers et al), molecular testing is becoming increasingly important for treatment decisions, and there may be benefit in waiting for these results. In addition, in 'real world settings', several barriers (e.g., lack of resources, correct diagnostic testing) often delay time to diagnosis, and initiation of therapy. We conducted a retrospective study in two academic centers in a major metropolitan area in the United States to evaluate the impact of DTI on the outcomes of patients with AML. Methods: We collected data from 196 patients who presented to George Washington University Hospital (120 patients) between June 2010 and July 2018 and Georgetown University hospital (76 patients) between January 2014 and December 2018. All patients were older than 18 years. Patients with acute promyelocytic leukemia and those who decided to pursue treatment elsewhere were excluded. Patients characteristics including age, gender, race, smoking past medical history and disease characteristics (Cytogenetics, FISH and NGS when available) were collected using retrospective chart review. Type of treatment received (low intensity vs high intensity), and the time from diagnosis to initiation of therapy were collected. We recorded mortality at day 30 and day 90. Multivariable logistic regression models were used to evaluate the association of DTI with mortality independently from patient age. Chi-square test was used to examine the association of 30- and 90-day mortality with DTI. Results: A total of 140 patients were used in the analysis, 71% of whom were treated within 5 days of diagnosis (DTI <1-5 days), 16% in 6-10 days, and 12% in >10 days. Incidence of 30-day mortality was 15%, 14%, and 0% (p=.24), while 90-day mortality was 28% 18%, and 13% for <1-5, 6-10, and >10 days respectively (p=.33). Neither association was statistically significant, and adjusting for age and type of therapy did not change the findings. Conclusion: Our data does not support that shorter DTI is associated with improved mortality regardless of age or type of therapy. Although there was no statistical significance, there was a numerical trend of improved mortality in patients with delayed DTI (6-10 days) compared to those with a DTI of <1-5 days. Larger prospective studies need to be conducted to investigate DTI in AML patients based on patient's age, disease characteristics, and treatment type. In particular, given the growing importance of knowing molecular mutations at diagnosis, used for both prognosis and incorporation of potential targeted agents, it will be important to understand how long we can safely wait to treat patients without affecting outcomes. Disclosures Lai: Jazz Pharma: Membership on an entity's Board of Directors or advisory committees; Jazz Pharma: Speakers Bureau; Astellas: Speakers Bureau; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Agios: Membership on an entity's Board of Directors or advisory committees.
Introduction: Systemic sclerosis (aka scleroderma) is an autoimmune disease with no known definitive etiology, but genetic, infectious, and non-infectious exposures have been associated with its occurrence. Previous studies have shown that systemic sclerosis can be a paraneoplastic phenomenon and may be associated with increased risk of malignancy, most commonly lung, skin, and breast cancers. The association of renal cell carcinoma with systemic sclerosis is rare. Case Description: Here, we present a case of a 75-year-old male patient with a rapidly progressive scleroderma despite the initial treatment with methotrexate and prednisone 5 mg daily. Shortly after the diagnosis of scleroderma, the patient was found to have a renal mass. The patient underwent a right partial nephrectomy revealing papillary renal cell carcinoma. The surgical margin was negative indicating complete removal of the cancer. The patient, later, developed scleroderma renal crisis and progressed to end-stage renal disease despite treatment with captopril, mycophenolate mofetil, plasmapheresis, and intravenous immunoglobulin. Conclusions: The purpose of this case report and literature review is to highlight that diffuse scleroderma can potentially be paraneoplastic from a renal cell carcinoma and to add more data to the literature given there are only a handful of reported cases. Our patient is unique in the sense that he was discovered to have renal cell carcinoma shortly after being diagnosed with scleroderma suggesting a paraneoplastic etiology yet continued to worsen despite full resection of the renal cell carcinoma. This is in contrast to the other reported cases of renal cell carcinoma associated scleroderma where scleroderma worsened around the time of the diagnosis of renal cell carcinoma and improved after nephrectomy. There also are case reports of the patients with renal cell carcinoma associated scleroderma where the patient had scleroderma for several years before the diagnosis of renal cell carcinoma, which raises the question, if scleroderma could also represent a risk factor for developing renal cell carcinoma.
PURPOSE: Hematology and oncology (HO) lags behind all medicine subspecialties in fellows under-represented in medicine (URM) despite a growing minority patient population. Websites have been effectively used in URM recruitment. We evaluated all US HO program websites to facilitate a more informed and URM-considerate recruitment. We also performed a stratified analysis on programs affiliated with National Cancer Institute (NCI) Designated Cancer Centers, National Comprehensive Cancer Center Network (NCCN) member institutions, and ranked as a top 50 cancer hospital by US News, given their stated commitment to outreach. MATERIALS AND METHODS: Websites of all 2019-2020 Accreditation Council for Graduate Medical Education–accredited HO programs were assessed for 28 informational and three diversity categories. Websites with > 70% of categories were comprehensive. Affiliation with NCI, NCCN, and US News was noted. RESULTS: One hundred fifty-six websites were analyzed: 20% were comprehensive and 22% had any diversity information. Inclusion of diversity content and being comprehensive were significantly associated ( P = .001). NCI, NCCN, and US News ranking were significantly associated with inclusion of more information in univariate analyses ( P < .001, P = .008, and P < .001, respectively). Multivariate analyses showed that US News ranking was significantly associated with more information ( P = .005). Diversity-related univariate and multivariate analyses showed a significant association with US News ranking ( P = .006 and P = .029, respectively). CONCLUSION: Most HO fellowship websites are not comprehensive and lack diversity content. Given COVID-19 travel restrictions limit in-person interviews, digital program presence remains an important opportunity. HO programs should offer comprehensive and inclusive websites to better inform applicants, including URM. This may increase institutional diversity and potentially improve URM representation in the HO workforce.
11004 Background: Fellowship in hematology and oncology (HO) is widely sought after but lags behind all other internal medicine subspecialties in attracting applicants underrepresented in medicine (URM). An approach to appealing to URMs involves preexisting in-person strategies but also adapting virtual tools to promote inclusion. Specifically, program websites serve as the first impressions of a program, as well as influence the perception of diversity and inclusion. We evaluated the content and diversity representation of HO program websites to facilitate a generally more informed and URM-considerate recruitment. Methods: The websites of 2019-2020 ACGME accredited HO programs were assessed between June 1st to July 1st, 2020. Data focused on 30 informational categories, derived from published methodology, along with three additional categories concerning diversity, based on suggestions for inclusive graduate medical education recruitment strategies, were compared using two-tailed t tests. We defined websites with 70% or more of the 30 informational categories as “comprehensive websites.” Affiliation with a National Cancer Institute (NCI) Designated Cancer Center, NCI Designated Cancer Center + National Cancer Center Network (NCCN) member institution, and a top 50 ranked cancer hospital by U.S. News was also considered in the analysis. Results: A total of 156 program websites were analyzed: 37.2% NCI; 19.9% NCCN; 29.5% U.S. News ranked. Only 31 (19.9%) were “comprehensive websites,” and 34 (21.8%) had information pertaining to at least one of the diversity categories. There was a significant association between inclusion of diversity content and being a “comprehensive website” (p = 0.001). Compared to those that were neither designated nor ranked, programs designated by NCI, NCCN, or ranked by U.S. News were more likely to have more complete information available (p < 0.001, = 0.008, and < 0.001, respectively). However, only programs ranked by U.S. News were more likely to include information about diversity on their websites (p = 0.006). Conclusions: The vast majority of HO fellowship program websites were not comprehensive, including a lack of diversity and inclusivity content. NCI designation, NCCN participation, and US News ranking were significantly associated with more complete fellowship websites. Given the context of the COVID-19 pandemic in which institution visitation is restricted, program websites may have elevated importance in recruitment. HO programs should direct resources to offering more complete and inclusive websites to better inform applicants, including URM residents.
BackgroundImmune-related adverse events (irAEs) are a unique characteristic of immune checkpoint inhibitors (ICIs) and can confer survival benefits. For example, melanoma patients who develop vitiligo as an irAE tend to have improved overall survival (OS), hypothesized to be due to molecular mimicry between similar antigens.1 2 Further analysis of the impact of irAEs on OS among real-world lung cancer patients is needed; this study addresses this need in a hospitalized population.3–5MethodsThis single-center retrospective cohort study collected data on a subset of lung cancer patients who received > 1 dose of an ICI (nivolumab or pembrolizumab) between 6/1/18 and 2/1/20 (n=210) and who were subsequently hospitalized and received > 1 dose of systemic corticosteroids for any indication (n=97). Patients were stratified according to whether or not they developed irAEs at any point. Clinical factors for data collection included: comorbidities, irAE development (organ and grade), cancer stage, ICI cycles, biomarkers, progression, and survival. OS analysis was calculated from the first dose of ICI to date of death or last known follow-up. To assess significance, the log-rank approximation of the chi-square test was used.ResultsKaplan-Meier survival analysis revealed that patients who developed irAEs (n=28, median OS 14.9 months) did not have an association with increased median OS when compared to patients without irAEs (n=69, 8.7 months, p 0.072) (table 1). The subgroup of patients who developed either colitis or pneumonitis had an increased median OS (n=15, 41.3 months, p 0.049) compared to patients without irAEs . Patients who only experienced grade ≥ 3 irAEs (n = 20, median OS 17.0 months, p 0.095) did not show any OS difference compared to patients without irAEs. Patients who developed ≥2 irAEs of any grade (n = 7, median OS 17.0 months, p 0.22) did not show any OS difference as compared to patients without irAEs.ConclusionsInitial analysis shows that while generalized irAEs in this hospitalized lung cancer population were not significantly associated with OS change, patients who developed pneumonitis and colitis were associated with treatment response and increased OS. Patients could be developing an interaction between pneumonitis and lung cancer analogous to the interaction between vitiligo and melanoma via molecular mimicry, resulting in improved OS. Thus, certain organ-related irAEs may indicate an immune response to ICIs depending on the malignancy being treated, correlating with improved prognosis.ReferencesBertrand A, Kostine M, Barnetche T, Truchetet M-E, Schaeverbeke T. Immune related adverse events associated with anti-CTLA-4 antibodies: systematic review and meta-analysis. BMC Med 2015;13:211.Teulings H-E, Limpens J, Jansen SN, et al. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: a systematic review and meta-analysis. J Clin Oncol 2015;33(7):773–81.Owen DH, Wei L, Villalona-Calero MA, et al. Impact of immune-related adverse events (irAE) on overall survival (OS) in patients treated with immunotherapy for non-small cell lung cancer (NSCLC). J Clin Orthod 2017;35(15_suppl):9080–9080.Haratani K, Hayashi H, Chiba Y, et al. Association of immune-related adverse events with nivolumab efficacy in non–small-cell lung cancer. JAMA Oncol 2018;4(3):374–8.Owen DH, Wei L, Bertino EM, et al. Incidence, risk factors, and effect on survival of immune-related adverse events in patients with non–small-cell lung cancer. Clin Lung Cancer 2018;19(6):e893–900.Ethics ApprovalThe study protocol was approved by Wake Forest Baptist Medical Center's institutional review board.Abstract 810 Table 1Results of irAE impact on median OS analysis
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