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The SMARCB1/INI1 gene was first discovered in the mid-1990s, and since then it has been revealed that loss of function mutations in this gene result in aggressive rhabdoid tumors. Recently, the term “rhabdoid tumor” has become synonymous with decreased SMARCB1/INI1 expression. When genetic aberrations in the SMARCB1/INI1 gene occur, the result can cause complete loss of expression, decreased expression, and mosaic expression. Although SMARCB1/INI1-deficient tumors are predominantly sarcomas, this is a diverse group of tumors with mixed phenotypes, which can often make the diagnosis challenging. Prognosis for these aggressive tumors is often poor. Moreover, refractory and relapsing progressive disease is common. As a result, accurate and timely diagnosis is imperative. Despite the SMARCB1/INI1 gene itself and its implications in tumorigenesis being discovered over two decades ago, there is a paucity of rhabdoid tumor cases reported in the literature that detail SMARCB1/INI1 expression. Much work remains if we hope to provide additional therapeutic strategies for patients with aggressive SMARCB1/INI1-deficient tumors.

Malignant SMARCB1/INI1-deficient extrarenal rhabdoid tumors are aggressive tumors that are extremely rare in adults. A 56-year-old male presented with the chief complaints of unilateral lower abdominal and pelvic pain. He underwent urgent surgical intervention and mass resection with tissue sampling. After pathology confirmed the diagnosis, systemic chemotherapy with vincristine, doxorubicin plus ifosfamide, and mesna was administered. Following treatment, he experienced a durable and long-lasting response to therapy for this aggressive and rare soft tissue sarcoma. To date, the patient remains in complete remission following the cessation of chemotherapy. Malignant SMARCB1/INI1-deficient extrarenal rhabdoid tumors are aggressive neoplasms that are extremely rare in adults. We report a rare case of such a tumor and review the literature for its molecular, clinical, and imaging features.

Primary rectal squamous cell carcinoma is rare compared to adenocarcinoma, which is the predominant histologic type most commonly discovered at the time of colorectal carcinoma diagnosis. Due to the infrequent nature of this malignancy, data on tumor pathogenesis and risk factors remains sparse. Moreover, no standardized therapeutic regimen exists. This report describes a case of advanced rectal squamous cell carcinoma diagnosed in a 46-year-old female who initially presented with abdominal pain. Her clinical course was uncomplicated and she responded well to the selected therapy. Much work remains to be accomplished for patients with rectal squamous cell carcinoma.

Inhibitors of cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein-1, and programmed death-ligand 1 have been shown to produce significant antitumor activity in multiple malignancies, and have become essential oncology standard-of-care therapies. Despite their success, the checkpoint inhibitors’ ability to amplify the immune system response against tumor cells has been associated with a unique panel of side effects known as immune-related adverse events. The involvement of the myocardium has been reported previously, but it’s remarkably uncommon. Even more noteworthy is that secondary autoimmune myocarditis and heart failure due to these medications are typically fatal.

3027 Background: Liquid biopsy is a promising, rapid and minimally invasive genetic test examining circulating tumor DNA. It offers a significant potential in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid cancer whose tumors were tested with the Guardant 360® (Guardant Health) assay between December 2018 and 2019. A follow-up analysis (censor date: 01/06/2021) was carried to assess the actual impact of testing results on treatment assignment and survival. Results: A total of 178 patients underwent testing. Mean age at diagnosis was 65 years. Median (m) Karnofsky Performance Scale was 90% and the majority of patients (89.9%) had ≥ stage III-B disease. Lung (LCa; 50.56%), breast (BCa; 17.42%) and colorectal (CRCa; 7.87%) cancers were the most common cancer types. A positive test was reported in 140/178 patients (78.7%); of those, 105/140 (75%) had an actionable mutation, either with an FDA-approved target-matched therapy (n = 32/105; 30.5%) or with a therapy outside current FDA indication (n = 73/105; 69.5%). In patients with no actionable mutation (n = 35/140; 25%), 85.7% (n = 30/35) had a signal-based clinical trial opportunity. The actual overall signal-based matching rate was 17.8% (24/135; vs. 82.2% no-match rate). Within candidates for FDA-approved treatment, 50% (16/32) received targeted therapy while only 6.9% (5/73) were treated with targeted agents outside current FDA indication: mean matching score (number of matched drugs/number of actionable mutations) was 0.6 (range: 0.33-2) and 0.8 (range: 0.17-2), respectively. Only 10% (3/30) were referred to signal-based clinical trials. Survival analysis of LCa, BCa and CRCa patients with actionable mutations who actually received any therapy (n = 66) revealed post-testing survival advantage for target-matched therapy (n = 22) compared to unmatched therapy (n = 44): overall survival (OS) was longer in the matched cohort (mOS: 13.3 months; 95% CI: 11.8-14.8 vs. 10.7 months; 95% CI: 9-12.4 in unmatched) but did not reach statistical significance ( P = 0.09). Progression free survival (PFS) was significantly longer in patients who received matched therapy (mPFS: 11.3 months; 95% CI: 9.9-12.7 vs. mPFS: 6.8 months; 95% CI: 5.1-8.5 in unmatched; P < 0.05). Conclusions: Implementation of liquid biopsy testing is feasible in community practice and impacts therapeutic choices in patients with advanced malignancies. Receipt of liquid biopsy-generated signal-matched precision therapies conferred added survival benefit compared to unmatched therapy. Larger sample size studies are needed to validate these findings.

3527 Background: Liquid biopsy is a promising and minimally invasive genetic test examining plasma circulating tumor DNA. Coupled with the rapidly developing next-generation sequencing (NGS) technologies, it holds the potential for implementation in selecting signal-matched therapeutic options. Methods: A retrospective chart review was conducted on adult patients with advanced solid tumors whose tumors were tested with Guardant360 assay, between December 2018 and December 2019. A total of 178 patients were referred for testing by 12 oncologists within a single community cancer center. Results: Referral rates varied widely (2.25% - 22%). The majority of patients (98%) were tested upfront for molecular marker evaluation, in either newly diagnosed advanced cancer patients, or in recurrent patients without enough tissue for testing. Other patients (2%) were evaluated after failure of 1 st line therapy to assess for acquired mutations. A total of 18 histological types were tested, with lung (LCa; n = 90; 50.56%), breast (BCa; n = 31; 17.42%), and colorectal (CRCa; n = 14; 7.87%) cancers being the most common types. In 86.11% of all tests (n = 180), ≥ 1 alteration was detected, while 13.89 % of tests did not reveal any tumor-related mutation, and were considered negative. The average number of alterations per test was 3.1 (±2.14; n = 481), and varied across types: CRCa (4.36), prostate cancer (2.73), BCa (2.97), and LCa (2.59), had the highest average number of alterations per test. Similarly, LCa (48.44%), BCa (19.13%), and CRCa (12.68%), harbored most of the detected somatic alterations (n = 481). Of all the alterations of practical significance (n = 457), TP53 (32.17%), PIK3CA (8.53%), EGFR (7.66%) and KRAS (7.22%), were the most commonly altered genes. Only 1 patient had a positive MSI-H status, amenable to immune-therapy. Of those with positive test results (n = 155), 31 (20%) had ≥ 1 FDA approved, target-matched therapeutic opportunity. Similarly, 71 patients (45.81%) had ≥ 1 target-matched therapeutic opportunity, outside current indications. Lastly, when no FDA-approved target-matched therapy was available (n = 39), results from liquid biopsy testing offered signal-based clinical trial opportunity in 39/39 patients. Conclusions: Implementation of NGS-based liquid biopsy testing is feasible within a community practice. In the era of precision oncology, such assays have the potential to expedite the efforts towards target-matched therapies and signal-based clinical trial opportunities. Further studies are warranted to identify the most-cost effective testing strategies.

e19505Background: Filgrastim-sndz was the first biosimilar granulocyte colony stimulating factor to be approved by the FDA for the same indications, including peripheral blood stem cell mobilizatio...

Locally advanced esophageal carcinoma is treated with multimodality therapy, utilizing the benefits of chemotherapy, radiation therapy, and esophagectomy with curative intent. At the time of posttherapy relapse, sites of disease include both local recurrence as well as distant disease. Notably, brain metastasis is an uncommon form of relapse for this malignancy. Human epidermal growth factor receptor 2 (HER-2) is a member of a family of receptors that are associated with cell proliferation, differentiation, migration, and adhesion. This receptor is overexpressed on the cell surface of a number of carcinomas and has been noted to be amplified in a proportion of gastroesophageal tumors. Additionally, an association between the presence of HER-2 overexpression and the development of brain metastases in breast cancers has been well described. A recent study has shown potential association between brain metastases from esophageal carcinoma and HER-2 overexpression. This association could have significant clinical impact in staging procedures, upfront therapy selection, and treatment choices for metastases to the central nervous system.

Acquired hemophilia A is an uncommon but potentially life-threatening clinical entity mediated by specific autoantibodies direct against coagulation factor VIII. It may be associated with a number of conditions such as solid malignancies, autoimmune diseases, lymphoproliferative disorders, and drugs. Early recognition of this entity is necessary to avoid a delay in treatment, which might lead to serious complications including severe bleeding and death. Hereby, we report a case of acquired hemophilia A caused by a commonly used drug, penicillin, as well as the first reported case, to our knowledge, of acquired Factor VIII inhibitor secondary to paclitaxel.

e23145Background: The advent of next-generation sequencing (NGS) for cancer holds promise for targeted therapy, but the practical issues surrounding integration of this testing into the community o...

To study if HER-2 overexpression by locally advanced esophageal cancers increase the chance of brain metastasis following esophagectomy.We retrospectively reviewed the medical records of esophageal cancer patients who underwent esophagectomy at University of Iowa Hospitals and Clinics between 2000 and 2010. Data analyzed consisted of demographic and clinical variables. The brain metastasis tissue was assayed for HER-2 overexpression utilizing the FDA approved DAKO Hercept Test(®).One hundred and forty two patients were reviewed. Median age was 64 years (36-86 years). Eighty eight patients (62%) received neoadjuvant chemoradiotherapy. Pathological complete and partial responses were achieved in 17 (19%) and 71 (81%) patients. Cancer relapsed in 43/142 (30%) patients. The brain was the first site of relapse in 9/43 patients (21%, 95% CI: 10%-36%). HER-2 immunohistochemistry testing of the brain metastasis tissue showed that 5/9 (56%) cases overexpressed HER-2 (3+ staining).HER-2 overexpression might be associated with increased risk of brain metastasis in esophageal cancer patients following esophagectomy. Further studies will be required to validate this observation.

e14572 Background: BM is historically an uncommon relapse pattern of EC. HER2 is a membrane tyrosine kinase that is overexpressed in various cancers as EC and breast cancer (BC). BM in BC patients ...