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Background: Infection with SARS-CoV-2 has led to a global pandemic and has significantly impacted the care of cancer patients. Breast cancer patients receiving active systemic therapy need protection against COVID19 but the efficacy of vaccines in this population is unknown. Although specific biomarkers associated with protection from SARS-CoV-2 infection have yet to be identified, measurement of serum antibody activity is generally accepted as a surrogate of in vivo humoral response to vaccine. This study evaluates the efficiency and durability of binding antibodies to SARS-CoV-2 spike (S) protein in response to COVID19 vaccine in breast cancer patients receiving systemic treatment. Methods: Breast cancer patients, who were unvaccinated, partially or fully vaccinated with Pfizer-BioNTech BNT162b2 (PF), Moderna mRNA-1273 (Mod) or Johnson & Johnson AD26.COV2.S (J&J) were enrolled in this prospective longitudinal study. Eligible patients were on systemic treatment with cytotoxic chemotherapy, chemotherapy plus a checkpoint inhibitor (CPI), CPI alone or a CDK 4/6 inhibitor. Longitudinal blood samples are being collected at baseline, prior to vaccination in unvaccinated patients (T0), 2 weeks after the first vaccine dose and before the second dose for the mRNA vaccines (T1), 1 month (T2), 3 months (T3), 6 months (T4) and 12 month post vaccination. For J&J, there was no T1 timepoint. Roche Elecsys® Anti-SARS-CoV-2 S receptor binding domain (RBD) antibody immunoassay was used to measure antibody titers (range 0.4 to 250 U/mL). Cut points of N% Seropositive (>0.8 U/mL)Mean Antibody Levels (U/mL)T0T1T2T3T0T1T2T3All subjects7510789810012.6102.3204.4214.6Chemotherapy50577961003.3105.6200.0250CDK 4/6 inhibitors15257510010013.786.8234.7205.8CPI + Chemotherapy82583100NA*62.8121.4177.5NA*CPI therapy20100100NA*0.46.82250NA*CPI=Checkpoint Inhibitors; *Timepoint for longitudinal samples not reached Citation Format: Cory Bivona, Kevin Li, Priyanka Sharma, Jianghua He, Grace Martin, Andrew K Godwin, Anthony Rooney, Stephen Williamson, Gary Doolittle, Weijing Sun, Bruce F Kimler, Anne P O'Dea, Lauren E Nye, Joseph P McGuirk, Ziyan Pessetto, Lisa Haney, Nicole Balmaceda, Laura Mitchell, Karissa Finke, Maggie Nelson, Dinesh Pal Mudaranthakam, Natalie Streeter, Stephanie Lafaver, Jaimie Heldstab, Qamar J Khan. Immunogenicity of SARS-CoV-2 vaccination in subjects on active treatment for breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-03.

Background Patients with multiple myeloma (MM) remain at an increased risk of infection due to the disease process, as well as the ensuing treatments. Methods We performed a systematic review to evaluate the monthly risk of grade III/IV infection, pneumonia, and neutropenia in patients with myeloma enrolled in randomized clinical trials (RCTs). Results The risk of grade III or higher infection, pneumonia, and neutropenia persists among all phases of treatment. There was no statistical difference in grade III or higher infection, pneumonia, and neutropenia between frontline and relapsed/refractory setting. In the maintenance setting, the complications of infection, pneumonia, and neutropenia were low, but not negligible. Three-drug regimens were no more likely than two-drug regimens to have an increased risk of Grade III or higher infection. Conclusions This is the first study to quantify the monthly risk of grade III or higher infection, pneumonia, and neutropenia across different treatment regimens in the frontline, maintenance, and relapsed/refractory settings. The results of our systematic review demonstrate a significant risk for severe infection, pneumonia, and neutropenia in patients with MM. Further studies are needed to determine the value of antibiotic prophylaxis in a broader myeloma patient population, as well as other approaches that will further mitigate the morbidity and mortality related to infection in this vulnerable patient population.

With advances in state-of-the-art technology, trendy diagnostic and prognostic molecular markers, and cutting-edge surgical techniques, the overall survival for patients with many types of cancers has improved. However, there is a disconnect between esophageal cancer and the acceleration in cancer care seen in other malignancies. Based on data reported by Surveillance, Epidemiology, and End Results Program (SEER), the 5-year survival rate for patients with esophageal cancer is only 19.9% [1]. Poor prognosis is likely due to an overwhelming number of patients with advanced disease during the time of diagnosis, and is also reflective of the unsatisfactory outcomes from current treatments. In this article, we will review the epidemiology and the recently revised staging of esophageal and esophagogastric junction cancers. We will discuss the current roles of endoscopic resection, surgery, radiation therapy, and systemic therapy used individually, or as components of multimodality treatment. We will describe the changes in treatment landscape with targeted therapy and immunotherapy. The focus of clinical investigations continues to shift from the traditional empiric chemotherapy to more individualized treatments based on molecular oncology and use of immunotherapy. Further identification of prognostic values may help clarify the optimal approach to treatment and management for patients with esophageal cancer, and hopefully improve survival. Clinical trials investigating strategies in prevention, early diagnosis, and treatment of early and advanced disease are guided by lessons learned in epidemiology, molecular genetics, pharmacogenomics, and precision medicine.

This Expression of Concern relates to the article ‘Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion’ by Andy R. Wolfe, Amanda Ernlund, William McGuinness, Carl Lehmann, Kaitlyn Carl, Nicole Balmaceda and Kristi L. Neufeld. J. Cell Sci. 2017 130 , 805-813 ([doi

Therapeutic strategies based on a specific oncogenic target are better justified when elimination of that particular oncogene reduces tumorigenesis in a model organism. One such oncogene, Musashi-1 (Msi-1), regulates translation of target mRNAs and is implicated in promoting tumorigenesis in the colon and other tissues. Msi-1 targets include the tumor suppressor adenomatous polyposis coli (Apc), a Wnt pathway antagonist lost in ∼80% of all colorectal cancers. Cell culture experiments have established that Msi-1 is a Wnt target, thus positioning Msi-1 and Apc as mutual antagonists in a mutually repressive feedback loop. Here, we report that intestines from mice lacking Msi-1 display aberrant Apc and Msi-1 mutually repressive feedback, reduced Wnt and Notch signaling, decreased proliferation, and changes in stem cell populations, features predicted to suppress tumorigenesis. Indeed, mice with germline Apc mutations (ApcMin) or with the Apc1322T truncation mutation have a dramatic reduction in intestinal polyp number when Msi-1 is deleted. Taken together, these results provide genetic evidence that Msi-1 contributes to intestinal tumorigenesis driven by Apc loss, and validate the pursuit of Msi-1 inhibitors as chemo-prevention agents to reduce tumor burden.

The journal is retracting ‘Suppression of intestinal tumorigenesis in Apc mutant mice upon Musashi-1 deletion’ by Andy R. Wolfe, Amanda Ernlund, William McGuinness, Carl Lehmann, Kaitlyn Carl, Nicole Balmaceda and Kristi L. Neufeld (2017). [J. Cell Sci. 130, 805-813][1] (doi: 10.1242/

Background Metastatic pancreatic neuroendocrine tumors (PNET) are generally not curable; however, some patients may have prolonged survival. Until recently, metastatic PNET were primarily managed with somatostatin-analogs. New developments demonstrating therapeutic value of temozolomide (TMZ) in these patients resulted in its off-label use in National Comprehensive Cancer Network guidelines. Given alone, or in combination with other therapies, TMZ is associated with improved clinical outcomes. However, serious hematologic adverse events (AEs) like agranulocytosis, lymphopenia and aplastic anemia are not uncommon. At the University of Kansas Cancer Center (KUCC), 3 patients with history of TMZ-treated metastatic PNET developed hematologic malignancies. The purpose of this study is to determine the incidence of secondary malignancies (SM) in this patient population. Methods A systematic review of all known clinical trials, case reports, and other relevant literature regarding PNET and TMZ published before September 2017 was conducted using PubMed, Embase, Cochrane Library, and the FDA Adverse Event Reporting System (FAERS). Results We analyzed 38 publications and 8,215 cases reported from FAERS. AEs ranged from agranulocytosis to myelodysplastic syndrome. No publications reported any SM. The 3 patients identified at KUCC are as follows: 1) 29-year-old female with TMZ-treated metastatic PNET developed acute myeloid leukemia with cytogenetics consistent with therapy-related leukemia. 2) 80-year-old male with TMZ-treated metastatic PNET developed diffuse large B-cell lymphoma. 3) 12-year-old male with TMZ-treated metastatic PNET developed high-grade T-cell lymphoblastic lymphoma. All these patients succumbed to their hematologic malignancies, and not the underlying PNET. Conclusions Although we observed 3 cases at KUCC, this retrospective review did not find any cases of SM in TMZ-treated metastatic PNET. We believe that the leukemogenic potential of TMZ is underreported. It is important for treatment guidelines to address this risk in the decision to pursue TMZ treatment. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

e18525 Background: Several recurrent genetic mutations have been described in acute myeloid leukemia (AML), which have both prognostic and therapeutic implications. Recurrent mutations in the Neurofibromin 1 ( NF1) gene are reported in 1-5 % of AML patients; however, there are limited data regarding its prognostic implications. Here, we report the outcomes for patients with newly diagnosed AML with a somatic NF1 mutation at our center. Methods: A retrospective chart review included patients with newly diagnosed AML at KUMC from 01/2016 through 09/2018. All patients had targeted next-generation sequencing (NGS) at diagnosis. Baseline characteristics were compared between patients with NF1 mutations and those who were wild-type using Fisher’s exact test for categorical variables, and the Wilcoxon rank-sum test for continuous variables. The primary outcome was overall survival (OS), which was measured from the time of diagnosis to the time of death from any cause. A stepwise Cox proportional-hazard model was used to adjust for potential confounders. Results: Data on 110 patients were included. Out of the 110 patients, 15 (13.6%) had a delectable NF1 mutation, while 95 (86.4%) patients were NF1 wild-type. The baseline characteristics of the two groups are displayed below. Median OS for patients with an NF1 mutation was 7.3 months, while it was 18.4 months for patients with NF1 wild-type, Log-rank test p-value 0.02. After adjusting for potential confounders, including age, ELN risk category, induction regimen, presence of other mutations such as TP53, the hazard of death remained significantly higher for patients with NF1 mutations, HR 2.4, CI (1.05-5.6), p-value 0.04. Conclusions: In this single-center retrospective study, the presence of a NF1 mutation was associated with worse overall survival in patients with newly diagnosis AML. [Table: see text]

Purpose: To determine the incidence of secondary malignancies in patients treated with temozolomide (TMZ) for metastatic pancreatic neuroendocrine tumors (PNET). Background: TMZ is an oral alkylating agent used to treat glioblastoma multiforme (GBM), refractory anaplastic astrocytoma (AA), and metastatic PNET. This imidazotetrazine analog of dacarbazine lacks the ability to directly crosslink DNA and is thought to be less leukemogenic than other alkylators. Given either alone, or in combination with other therapies, TMZ is associated with improved clinical outcomes. However, serious hematologic adverse events (HAEs) like agranulocytosis, lymphopenia and aplastic anemia are not uncommon. Until recently, metastatic PNET was primarily managed with somatostatin-analogs, but with more reports demonstrating therapeutic activity of TMZ-based regimens, it is anticipated that more patients with metastatic PNET will be exposed to TMZ. Methods: To determine the incidence of secondary malignancy in TMZ-treated PNET, a systematic review of all known clinical trials, case reports, and other relevant literature regarding PNET and TMZ published before September 2017 was conducted using PubMed, Embase, Cochrane Library, and the FDA database. Results: Twenty-one publications, including clinical trials, meta-analyses, case reports, and cohort studies were analyzed. HAEs ranged from agranulocytosis to myelodysplastic syndrome. No publications reported any secondary malignancies. Incidentally, at the University of Kansas Medical Center, 3 patients with TMZ-treated PNET developed hematologic malignancies. A 29-year-old female with metastatic PNET was treated with TMZ and subsequently developed acute myeloid leukemia (AML) with cytogenetics consistent with therapy-related leukemia. The second patient with TMZ-treated metastatic PNET developed diffuse large B-cell lymphoma. These two patients both had aggressive disease that was not responsive to multiple rounds of treatment. They succumbed to their hematologic malignancy, and not from metastatic PNET. The third patient is a 29-year-old who was recently diagnosed with high-grade T-cell lymphoblastic lymphoma and is currently undergoing treatment for his lymphoma. Conclusion: This review did not find any cases of secondary malignancy in TMZ-treated metastatic PNET. Yet, at our own institution we have identified 3 cases of secondary hematologic malignancies in patients treated with TMZ for PNET. We believe that the leukemogenic potential of TMZ is underreported and anticipate increased reports of secondary malignancy as the use of TMZ increases. It is important for treatment guidelines to address this risk in the decision to pursue TMZ treatment. Appropriate dosing, proper follow-up and surveillance, especially in patients who are able to live long enough to develop these hematologic cancers, is crucial. Citation Format: Nicole Balmaceda, Sunil Abhyankar, Tyler Mouw, Joaquina Baranda. Secondary malignancies in temozolomide-treated metastatic pancreatic neuroendocrine tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 599.