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Inflammatory myofibroblastic tumors (IMTs) are intermediate-grade mesenchymal neoplasms commonly characterized by chromosomal rearrangements causing constitutive activation of anaplastic lymphoma kinase (ALK) and/or ALK mutations causing reduced sensitivity to ALK tyrosine kinase inhibitors (TKI). We present a patient with an IMT who initially responded to first-line alectinib, but who later suffered disease relapse and presently survives with moderate residual disease after receiving second-line lorlatinib. Biopsy specimens were analyzed using next generation sequencing (DNA-seq and RNA-seq) and reverse phase protein microarray (RPPA) as part of an institutional Molecular Tumor Board (MTB) study. An EML4-ALK rearrangement and EGFR activation (pEGFRY1068) were present in both the primary and recurrent tumors, while a secondary ALK I1171N mutation was exclusive to the latter. EGFR signaling in the background of a secondary ALK mutation is correlated with reduced ALK TKI sensitivity in vitro, implicating an important mechanism of drug resistance development in this patient. The RPPA results also critically demonstrate that ALK signaling (ALKY1604) was not activated in the recurrent tumor, thereby indicating that standard-of-care use of third- or fourth-line ALK TKI would not likely be efficacious or durable. These results underscore the importance of real-time clinical integration of functional protein drug target activation data with NGS in the MTB setting for improving selection of patient-tailored therapy.

PURPOSE:The COVID-19 pandemic has posed significant challenges in the care of patients with cancer, including how to manage outpatients who are COVID-positive but do not require hospitalization. We explored the use of a remote patient monitoring (RPM) program to care for such outpatients.METHODS:Consecutive patients who were tested for COVID-19 because of symptom onset but were clinically stable were offered enrollment into a pilot RPM program. Patients were provided equipment for vital sign measurements and a computer tablet to enter results three times per day. The results were monitored centrally by clinical staff. The goal was to closely monitor patients and escalate care as warranted.RESULTS:Between March and June of 2020, 29 patients were approached and 26 were enrolled. The mean age was 57 years old (range, 30-88), 14 were women, and patients remained in the program for an average of 16 days (range, 2-63). Twenty-four patients (83%) were on active anticancer therapy. During that time period, only one patient was admitted to the hospital for worsening respiratory symptoms. The percentage of days during which at least one set of data and all three sets of data were entered was 97.2% and 65.7%, respectively. There was no association between the demographic factors of age, sex, or the reason for being monitored with the level of engagement ( P > .05).CONCLUSION:In this pilot study, patients with cancer were readily enrolled in a remote home monitoring program. Monitoring was feasible, and there was a high rate of engagement with the program. The role of RPM should be further tested as the COVID pandemic continues.

TAPUR is a phase II basket trial evaluating the antitumor activity of commercially available targeted agents in patients with advanced cancer and genomic alterations known to be drug targets. The results of a cohort of patients with colorectal cancer (CRC) withEligible patients had advanced CRC, no standard treatment options, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, tumors withThirty patients were enrolled from August 2016 to August 2018; all had CRC with aThe combination of C + V has antitumor activity in heavily pretreated patients with CRC with

PURPOSE The TAPUR Study is a phase II basket trial that aims to identify signals of antitumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known to be drug targets. Results in a cohort of patients with metastatic breast cancer (mBC) with high tumor mutational burden (HTMB) treated with pembrolizumab are reported. METHODS Patients with advanced mBC received standard doses of either 2 mg/kg or 200 mg infusions of pembrolizumab every 3 weeks. Simon's two-stage design was used with a primary study end point of disease control (DC) defined as objective response or stable disease of at least 16 weeks duration. If two or more patients in stage I achieved DC, the cohort would enroll 18 additional patients in stage II. Secondary end points include progression-free survival (PFS), overall survival, and safety. RESULTS Twenty-eight patients were enrolled from October 2016 to July 2018. All patients' tumors had HTMB ranging from 9 to 37 mutations/megabase. DC and objective response were noted in 37% (95% CI, 21 to 50) and 21% of patients (95% CI, 8 to 41), respectively. Median PFS was 10.6 weeks (95% CI, 7.7 to 21.1); median overall survival was 30.6 weeks (95% CI, 18.3 to 103.3). No relationship was observed between PFS and tumor mutational burden. Five patients experienced ≥ 1 serious adverse event or grade 3 adverse event at least possibly related to pembrolizumab consistent with the product label. CONCLUSION Pembrolizumab monotherapy has antitumor activity in heavily pretreated patients with mBC characterized by HTMB. Our findings support the recent US Food and Drug Administration approval of pembrolizumab for treatment of patients with unresectable or metastatic solid tumors with HTMB without alternative treatment options.

PURPOSE The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non–small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported. METHODS Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon’s two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety. RESULTS Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting. CONCLUSION Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets. With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations. Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/m2 over 60 min). A Simon two-stage design, requiring ten patients in stage I, was employed per each disease-specific cohort. The primary endpoint was disease control (objective response or stable disease for at least 16 weeks). If two or more patients in stage I achieved disease control, the cohort would enroll 18 more patients in stage II. Power and alpha of the design are 85% and 10%, respectively. Secondary endpoints included progression-free survival, overall survival, and safety. Patients with BC (n = 10), NSCLC (n = 10), and OC (n = 29) were enrolled between June 2016 and September 2018. No objective responses or stable disease for at least 16 weeks were observed in the BC and NSCLC cohorts. No objective responses and four patients with stable disease for at least 16 weeks were observed in the OC cohort. Six of 49 patients reported grade 3 or higher adverse events or serious adverse events at least possibly related to cetuximab. Cetuximab does not have clinical activity in patients with advanced BC, NSCLC, and OC without KRAS, NRAS, or BRAF mutations. NCT02693535 (26 February, 2016).

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non-small-cell lung cancer (NSCLC) withEligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC withTwenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting.Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with

Diffuse malignant peritoneal mesothelioma (DMPM) is a rare malignancy associated with poor outcomes. Recent reports have shown longer survival with radical surgery, usually combined with intraperitoneal chemotherapy. However, surgical interventions in these patients have not been extensively studied at a population level. The objective of this retrospective cohort study is to assess the prevalence of surgical and nonsurgical interventions for DMPM patients, the influence of surgery on survival outcomes, and the associations between demographic and clinical factors with treatments and outcomes. This study included adult patients diagnosed with DMPM from 2003 to 2014 and registered in the National Cancer Database (NCDB). The primary outcome was overall survival. Histologically confirmed mesothelioma was defined using International Classification of Diseases (ICD)-3 codes 9050/3, 9051/3, 90523, and 9053/3 and peritoneum as primary affected organ using ICD codes C17-19, C22-24, C26, C42, C48, and C76. Relationships between demographic and clinical variables, surgical treatments, and survival outcomes were evaluated using logistic and Cox modeling and log-rank tests. A total of 2062 patients were identified, of whom 1055 (51%) did not receive any surgery while 701 (34%) received radical surgery. Patients receiving radical surgery had overall survival of 38.4 months compared with 7.1 months for patients without surgery (p

This report presents the American Society of Clinical Oncology’s (ASCO’s) evaluation of the adaptations in care delivery, research operations, and regulatory oversight made in response to the coronavirus pandemic and presents recommendations for moving forward as the pandemic recedes. ASCO organized its recommendations for clinical research around five goals to ensure lessons learned from the COVID-19 experience are used to craft a more equitable, accessible, and efficient clinical research system that protects patient safety, ensures scientific integrity, and maintains data quality. The specific goals are: (1) ensure that clinical research is accessible, affordable, and equitable; (2) design more pragmatic and efficient clinical trials; (3) minimize administrative and regulatory burdens on research sites; (4) recruit, retain, and support a well-trained clinical research workforce; and (5) promote appropriate oversight and review of clinical trial conduct and results. Similarly, ASCO also organized its recommendations regarding cancer care delivery around five goals: (1) promote and protect equitable access to high-quality cancer care; (2) support safe delivery of high-quality cancer care; (3) advance policies to ensure oncology providers have sufficient resources to provide high-quality patient care; (4) recognize and address threats to clinician, provider, and patient well-being; and (5) improve patient access to high-quality cancer care via telemedicine. ASCO will work at all levels to advance the recommendations made in this report.

The Targeted Agent and Profiling Utilization Registry (TAPUR) Study, a phase II basket study, evaluates anti-tumor activity of commercially available targeted agents in patients with advanced cancers harboring genomic alterations known as drug targets.With no known genomic targets predictive of sensitivity to cetuximab, cetuximab was evaluated in patients with breast cancer (BC), non-small cell lung cancer (NSCLC), and ovarian cancer (OC), without KRAS, NRAS, or BRAF mutations.Eligible patients with advanced BC, NSCLC, and OC received a cetuximab loading dose, then weekly infusions (250 mg/mPatients with BC (n = 10), NSCLC (n = 10), and OC (n = 29) were enrolled between June 2016 and September 2018. No objective responses or stable disease for at least 16 weeks were observed in the BC and NSCLC cohorts. No objective responses and four patients with stable disease for at least 16 weeks were observed in the OC cohort. Six of 49 patients reported grade 3 or higher adverse events or serious adverse events at least possibly related to cetuximab.Cetuximab does not have clinical activity in patients with advanced BC, NSCLC, and OC without KRAS, NRAS, or BRAF mutations.NCT02693535 (26 February, 2016).

3561 Background: BRAF V600E+, MSS mCRC patients comprise up to 10% of advanced CRC. They have a poor prognosis with median survivals typically

Background: Pancreatic adenocarcinoma is associated with a very poor prognosis, with a 5 year survival of ∼7.2%. Vitamin D has long been evaluated for benefit as a protective agent and treatment for malignancies. Although cancer incidence and outcomes have been tied to vitamin D levels, there is no clear evidence that supplementation of vitamin D improves outcome in pancreatic cancer to date. Case Presentation: We present a patient who errantly took supratherapeutic doses of vitamin D 50,000 U daily, achieving a serum 25(OH)D level of more than 150 mg/mL, with no appreciable side effects. Conclusion: Her disease was stable for 8 months off of conventional treatment, although it is unclear whether this was related to vitamin D supplementation.

129 Background: KRAS and NRAS (RAS) mutations are considered driver mutations in gastrointestinal malignancies such as colorectal and pancreatic cancer. Our institution obtains broad molecular testing (commercial panels with full exon coverage of at least 300 genes) for all stage IV gastrointestinal malignancies that are reviewed at an internal molecular tumor board (MTB). The MTB subjectively felt there was less benefit from comprehensive molecular testing in RAS mutant tumors and wished to quantify this using standardized analysis according to validated guidelines. Methods: We performed a retrospective cohort study of 209 consecutive genomic sequencing results of advanced gastrointestinal malignancies at our institution dating from March 2016 until December 2019. We compared the number of “targetable” mutations in the RAS mutant and wild type (WT) malignancies, as analyzed by an interpretation service according to the Association of Molecular Pathology (AMP) guidelines. A lower AMP score corresponds to a higher level of evidence as a predictive biomarker. We also compared molecular tumor board specific recommendations for each group (excluding recommendations regarding RAS such as EGFR mAbs). Results: There were 134 RAS mutant and 75 RAS WT cases. Alterations with AMP scores of 1A,1B, and 1C were more commonly seen in the RAS WT population 18/75 and 9/134 respectively (24.0% versus 6.7% p-value=0.0004). 39 of 75 cases in RAS WT and 27/134 in RAS mutant (52.0 versus 20.1%, p-value

Background: The TAPUR Study is a phase II multi-basket study that evaluates the anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations known to be drug targets. Results in two cohorts of BC and NSCLC pts each without reported KRAS, NRAS, BRAF mutationstreated with C are reported. Methods: Simon’s optimal two stage design was used to test the null hypothesis of 15% response rate versus the alternative of 35%. Power and alpha were set at 85% and 10%, respectively. Response was assessed per RECIST v1.1. This design requires 10 pts in stage 1 and if Results: Ten pts were enrolled in the BC cohort from June 2016 to May 2018. Ten pts were enrolled in the NSCLC cohort from January 2017 to May 2018. Pts received C at an initial intravenous infusion of 400 mg/m2 over 120 minutes and subsequent weekly infusions of 250 mg/m2 over 60 minutes. All pts are included in the data analysis for demographics, safety, PFS and OS (Table 1). No ORs or SD at 16 wks were observed in either cohort and both were therefore closed. Grades 3-4 adverse events (AEs) at least possibly related to drug are required to be reported. A single grade 3 AE of hypomagnesemia was reported in the NSCLC cohort as possibly related to C. Conclusions: Results from these cohorts suggest monotherapy with C does not have clinical activity in BC or NSCLC pts without reported KRAS, NRAS, BRAF mutations. Other treatments should be considered for these pts, including treatments offered in clinical trials. Table 1:Baseline demographics, clinical characteristics and outcomes by cohortCetuximab targeting tumors without reported KRAS, NRAS, BRAF mutationsTumor TypeBC (N=10)NSCLC (N=10)Median age, yrs (range)59 (45, 65)60 (55, 82)Male, %060ECOG Performance Status, %01260301010900Median PFS, wks (90% CI)6.7 (4.0, 7.9)8.0 (7.6, 8.4)Median OS, wks (90% CI)11.0 (4.9, 30.1)19.6 (8.6, 25.6)Drug-related AEs, grades 3-4 (% of pts)010 Citation Format: Julie Fisher, Elizabeth Garrett-Mayer, Susan Halabi, Pam K. Mangat, Ricardo H. Alvarez, Timothy L. Cannon, Pamela Crilley, Theodore Pollock, Tareq Al Baghdadi, Jared A. Cotta, Andrew L. Rygiel, Kaitlyn R. Antonelli, Samiha Islam, Suanna S. Bruinooge, Richard L. Schilsky. Cetuximab (C) in patients (Pts) with breast cancer (BC) and non-small cell lung cancer (NSCLC) without reported KRAS, NRAS, BRAF mutations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT135.

e18001 Background: Patient engagement in medical decision-making improves patient related outcomes through compliance and patient satisfaction. The Inova Schar Cancer Institute (ISCI) has a weekly molecular tumor board (MTB) to match comprehensive genomic sequencing results with targeted therapies for patients. The ISCI MTB invites patients to attend and engage in the MTB discussion. We performed a pilot study to investigate the feasibility and satisfaction in patients who attended MTB. Methods: During the time of this study, August 2017 through October 2018, 139 patients were presented and all 20 who were able to attend MTB completed pre-and post- MTB surveys. Patients who did not attend were either not invited by their primary oncologist, unable to attend, or chose not to attend. The survey included six questions related to comprehension, engagement, and satisfaction with the treatment team. Results: There was a statistically significant change for the question “I am satisfied with how well informed I am about targeted therapy” with p = 0.016. All 20 patients answered positively that it was beneficial for them to attend. Many patients expressed concerns about their difficulty understanding the technical aspects of the meeting. Conclusions: Patients who attended MTB reported a higher level of satisfaction after MTB attendance as compared to before MTB. This may reflect a sense of engagement in shared decision making rather than comprehension of genomic information. A more holistic method of studying this practice would include sampling a larger patient population and a formal evaluation of the physicians’ experience with patients attending. Supported by philanthropic funds from the Inova Schar Cancer Institute.

9041 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of NSCLC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced NSCLC, no standard treatment options, measurable disease, ECOG PS 0-2 and adequate organ function. Genomic testing was performed using commercially available tests. Pts matched to P had NSCLC with CDKN2A loss or mutation and no RB mutations. A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-nine pts were enrolled from January 2017 to June 2018; 1 pt was unevaluable for response but is included in safety analyses. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off. Demographics and outcomes are summarized in Table (N = 28). One PR and 6 SD16+ were observed for a DC rate of 29% (90% CI, 15% to 37%). 10 pts had at least one grade 3 or 4 AE or SAE at least possibly related to P with the most common being cytopenias. Other grade 3-4 AEs or SAEs at least possibly related to P included fatigue, anorexia, febrile neutropenia, myocardial infarction, sepsis, vomiting, and hypophosphatemia. Conclusions: Monotherapy with P demonstrated evidence of anti-tumor activity in heavily pre-treated NSCLC pts with CDKN2A loss or mutation . Additional study is warranted to confirm the efficacy of P in pts with NSCLC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]

We compared the effect of order of administration of investigational alphavirus vaccines on neutralizing antibody response. Volunteers who received the inactivated eastern and western equine encephalitis (EEE and WEE) vaccines before live attenuated Venezuelan (VEE) vaccine had significantly lower rates of antibody response than those receiving VEE vaccine before EEE and WEE vaccines (66.7% vs. 80.6%; p = 0.026). The odds of having a VEE antibody non-response among those initially receiving EEE and WEE vaccines, adjusted for gender, were significant (odds ratio [OR] = 2.20; 95% CI = 1.2–4.1 [ p = 0.0145]) as were the odds of non-response among females adjusted for group (OR = 1.81; 95% CI = 1.2–2.7 [ p = 0.0037]). Antibody interference and gender effect have major implications for vaccine strategy among those receiving multiple alphavirus vaccines and those developing next generation vaccines for these threats.

DOI: 10.1200/JCO.2015.62.7505 Although I have lived the majority of my life in New Jersey, Utah has always felt like home. Three of my grandparents were multigenerational Utahns, of pioneer stock, and the other grandparent grew up in nearby Idaho. Our family disrupted this pattern when my father pursued a position as a materials science professor that eventually led him to Rutgers University. I had only two sisters, but our extended family, like most Mormon families, is substantial. I have 32 first cousins, and my wife (also from Idaho) has more than 50. Being the only oncologist our family knows, I have become aware of most relatives, relatives of relatives, or friends of relatives with cancer. Although I practice on the East Coast, I have a large virtual consulting service as a result of this extensive Utah and Idaho network. A random call or text message from a relative almost invariably means somebody they know has cancer. One such text was received last summer on a sweltering night in Alexandria, Virginia, where I now live. The text message was from a relative in Utah who asked, “any chance that somebody treating a melanoma with herbs will be OK”? I thought back to a patient I had just seen in my practice during the month before this text message. An educated man, an engineer at a military base, had used a recipe he found on the Internet to treat a melanoma on his left shoulder. He called the application a “slurry,” and said that it contained multiple herbs and also included eggplant and a flower called bloodroot. Applying this slurry induced a large scar on his left shoulder. More than 1 year later, he came to my office because of a 4-cm lymph node in his left axilla. A positron emission tomography scan revealed lung metastases. Utah is known as the epicenter of the natural supplement industry. It is, by some reports, the second biggest industry in the state. Many of these products are sold by multilevel marketing companies. Although these companies must, by law, tell you that there is no evidence of efficacy in cancer, much of the marketing is performed by their vast network of sales people. Many of these sales people are ostensibly customers who dabble in sales, with the goal of sharing these supplements, vitamins, or essential oils with friends and perhaps making a buck or two along the way. Although the executives of these pyramid-structured companies, perched in their offices with views of the Wasatch Mountains, are undoubtedly compliant with the law, many patients report that the downstream salespeople will often share testimonials of efficacy in cancer. The appeal of supplements for cancer treatment is by no means limited to the mountain states, but it seems to be especially common within my relatives’ social network. I made a call to this Utah relative, who told me what he knew of the situation. It was his sister-inlaw, whom I will call Katie for the purpose of the story, who had developed a nodular melanoma on her face. She was treating it topically and orally with a combination of herbs and had reported significant shrinkage. My relative explained that Katie had expressed some ambivalence toward the medical community and that she and her husband had sent a group e-mail to relatives to let them know that imploring them to see “a real doctor” would not be productive. Nonetheless, considering the perilous sounding melanoma, and my recent experience with the engineer, I resolved to insert myself into their situation. That night I wrote an e-mail, quite heartfelt, pleading them to reconsider. I pursued a more deferential approach, given that they sounded distrustful of physicians. Without being too forceful, I noted the gaps in my knowledge about herbal treatment but asked them to deeply consider the serious nature of the situation. Would they be amenable to being evaluated by both an herbalist and a dermatologist? They replied to my e-mail and wished to initiate a dialogue. For a better evaluation, they proposed a video call so that I could see the lesion. Our conversation took place with Katie and her husband Eric sitting on the couch in their living room. It was after 10:00 pm EST, and they had just put their daughter to bed. I had assumed they were relatively young but did not anticipate that they would appear to be not much beyond college age. They were attractive people, and the image on my smartphone screen resembled a photo from a clothing catalog. After an exchanged of niceties, they zoomed in on the lesion. The epicenter of the lesion was on her right forehead, just superior and lateral to her right JOURNAL OF CLINICAL ONCOLOGY A R T O F O N C O L O G Y VOLUME 33 NUMBER 26 SEPTEMBER 1

Opinion statement: The addition of targeted therapy to a 5-FU chemotherapy backbone is now a standard of care in metastatic colorectal cancer. Epidermal growth factor receptor (EGFR) inhibitors have been demonstrated to improve progression-free survival (PFS) and overall survival (OS) in the first line for patients with tumors that do not harbor KRAS exon 2 mutations. Eligibility criteria for most clinical trials involving EGFR inhibitors in recent years have used the absence of KRAS exon 2 mutation as the sole criteria for entry, as this specific mutation has been consistently shown to be predictive of a poor response to EGFR inhibitors. However, expanded analyses of first-line metastatic trials reveal that other RAS mutations, such as other KRAS mutations in exons 3 and 4, along with NRAS mutations, are predictive of poor responses to EGFR inhibitors as well. Testing for a full panel of these RAS mutations should be done prior to initiating treatment with an EGFR inhibitor. Further clinical trials are required to determine the predictive impact of each of these individual mutations. To date, they have been analyzed in the aggregate. The addition of targeted therapy, bevacizumab or an EGFR inhibitor, to a chemotherapy backbone should be considered for all appropriate patients. The relevant clinical trials that evaluated patients without any RAS mutation and compared an EGFR inhibitor to chemotherapy alone show a distinct advantage in overall survival and progression-free survival to the groups that received EGFR inhibition. The largest trial that compared bevacizumab with an EGFR inhibitor in the first line, CALGB/SWOG 80405, did not show a statistically significant difference between the two groups, making the use of bevacizumab, cetuximab, or panitumumab reasonable in the first line.

The antibody profile during and after the six-dose primary vaccination series with anthrax vaccine adsorbed (AVA, Biothrax) was characterized in 86 human volunteers. Ninety-three percent of recipients developed IgG antibodies to Bacillus anthracis protective antigen (PA) after two doses, and 100% were seropositive after dose #3. Geometric mean concentrations (GMC) of IgG to PA measured before and after each dose were significantly lower after injection #3 (peak GMC=146.65 microg/mL, trough GMC=15.16 microg/mL) than after injections #4 (peak GMC=430.46 microg/mL, trough GMC=94.57 microg/mL), #5 (peak GMC=415.05 microg/mL, trough GMC=81.94 microg/mL), or #6 (peak GMC=401.16 microg/mL, trough GMC=96.19 microg/mL) (por=0.0001 for each); but not between injections #4 and #5, #5 and #6, or #4 and #6 (por=0.7923 for each). Decay rates for IgG to PA were significantly faster after injection #3 (half life [T1/2]=39.21 days) than after injections #4 (T1/2=72.03 days), #5 (T1/2=70.14 days), and #6 (T1/2=74.59 days) (por=0.0282 for each). Toxin neutralizing assay (TNA) antibody patterns generally paralleled those for IgG to PA. The 6-month dose in the AVA primary series appears to be critical in sustaining IgG to PA concentrations in a substantial proportion of recipients.

483 Background: Inova Schar Cancer Institute formed a molecular tumor board in early 2016 to identify treatment options for patients with gastrointestinal malignances based on molecular testing and to track outcomes. Methods: From March 2016 to June 2017, 78 patients with advanced gastrointestinal malignancies were presented at our molecular tumor board. The most common mutations, the percentage of patients who received targeted therapies, responded to targeted therapies, died or went on hospice prior to receiving a recommended therapy, and had an available Association of Molecular Pathology Tier 1 or Tier 2 recommendation available were reviewed retrospectively. We also compared the overall survival of patients who received a new treatment after MTB compared to those who did not. N-of-One, Inc. provided curation of molecular testing and participated in the MTB. Results: 78 patients with gastrointestinal cancers were presented between March 2016 and June 2017. Thirteen (19%) patients received targeted therapy and 31% had partial response, 15% had Stable Disease, and 54% had progression of disease. 12 patients (15%) died or went on hospice before recommendations could start and 11 patients (14%) are waiting to start recommended therapy. 38 (49%) patients did not have a mutation that prompted a MTB recommendation. Median OS of the 33 patients who started a new therapy (including chemotherapy or unrelated clinical trials) after MTB was 15.3 months vs. 11.5 months in 40 patients who continued current therapy (P = 0.016 Wilcoxon). The three most common mutations detected were TP53, KRAS, and APC. The majority of cases had more than one variant. 18% of cases had a variant classified as Tier 1; 74% of cases had a variant with the highest AMP classification of Tier 2. Conclusions: The majority of patients with Gastrointestinal malignancies presented to the Inova MTB had a finding that supported a molecularly-guided therapy, with a small but meaningful number of partial responses. Barriers to the use of molecular guided therapy included molecular testing and presentation at a late disease stage, and alternative chemotherapeutic options.

e15515 Background: Gastric Cancer mortality rates in Central and South America are among the highest in the world. Our institution has monitored a cohort of patients who have presented with metastatic gastroesophageal cancer, age 40 or below. Methods: After observing multiple cases of advanced gastric cancer in young immigrants from Latin America, we performed a retrospective cohort study at Inova Fairfax Hospital, a 1000 bed tertiary care center in Northern Virginia. We reviewed our cancer registry from 2013-2016, to identify all patients, age 40 or below, with stage IV gastric adenocarcinoma. We also reviewed the percentage of hispanic patients in our cancer registry for all cancer diagnoses, for comparison. Results: There were thirteen patients with stage IV gastric cancer who were aged 40 or below found in our registry. Ten of the thirteen patients (76.9%) were from Latin America (see Table 1), with the majority of those being from either El Salvador or Honduras. All thirteen cases were notable for signet ring cell differentiation. Hispanic patients make up only 8.3% of the total subjects and 12.9% of gastric cancer subjects in the Inova Fairfax Hospital Cancer registry during that same time period. Conclusions: Stage IV signet ring cell gastric cancers have occurred frequently at our tertiary care center among young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]

Rift Valley fever (RVF) virus causes serious and fatal disease in animals and man. To protect personnel who work with RVF virus in the laboratory, or troops who may be exposed to this virus, the US Army successfully developed an improved version of inactivated RVF vaccine, TSI-GSD-200. From early 1986 to late 1997, 598 at-risk workers at the US Army Medical Research Institute of Infectious Diseases (USAMRIID) were vaccinated as part of an occupational safety and health program. The subjects of this study received three subcutaneous doses (0, 7 and 28 days) of 0.5 ml of TSI-GSD-200. A total of 540 vaccinees (90.3%) initially responded (group A) with an 80% plaque-reduction neutralization antibody titer (PRNT80) ofor =1:40; whereas 58 subjects (9.7%) were initial nonresponders (group B) failing to achieve this titer. Volunteers who either failed to respond or who achieved a titer ofor =1:40 but whose titer waned below 1:40 were boosted 1-4 times with the same vaccine. Among 247 group A subjects who received the first recall injection, 242 (98%) were successfully boosted, achieving a PRNT80or =1:40. Thirty-three of 44 (75%) initial nonresponders were converted to responder status after the first booster, which is a lower rate than that of group A (P0.001). After the primary series and the first booster, Kaplan-Meier analysis showed 50% probability of group A members maintaining a titer ofor =1:40 for approximately eight years; whereas group B had a 50% probability of maintaining a titer for only 204 days. Group A immune response rates to boosts 1-4 ranged from 87 to 100% with geometric mean titers (GMTs) ranging from 80 to 916. Boosts 1-4 immune response rates of group B volunteers ranged from 67 to 79% with GMTs ranging from 90 to 177. Minor side effects to TSI-GSD-200 were noted in 2.7% of all vaccinees after primaries and 3.5% of all vaccinees who had primaries and up to four boosters. We conclude that the use of TSI-GSD-200 is safe and provides good long-term immunity in humans when the primary series and one boost are administered.

Learning Objectives After completing this course, the reader will be able to: Compare the risk of secondary cancer versus benefits of maintenance therapy for women with ovarian cancer who have a complete response to pegylated liposomal doxorubicin.Explain the need to perform regular and frequent oral examinations in women with ovarian cancer who received treatment with pegylated liposomal doxorubicin. CME This article is available for continuing medical education credit at CME.TheOncologist.com Purpose. To describe occurrences of oral squamous cell carcinoma (SCC) in patients who had received long-term pegylated liposomal doxorubicin (PLD) for ovarian cancer. Patients and Methods. In our cohort of patients on maintenance PLD for ovarian and related mullerian epithelial malignancies, we encountered two patients with invasive SCC of the oral cavity (one of them multifocal) and one with high-grade squamous dysplasia. Review of patients at our institution receiving PLD for recurrent ovarian cancer identified three additional patients. The duration of treatment, cumulative PLD dose, human papillomavirus (HPV) positivity, BRCA status, stage at diagnosis, outcome, and other characteristics are reviewed. Results. All five cases were nonsmokers with no known risk factors for HPV and four were negative for p16 expression. Four of the patients had known BRCA mutations whereas one tested negative. Cumulative doses of PLD were >1,600 mg/m2 given over 30–132 months. Three had SCCs staged as T1N0 oral tongue, alveolar ridge (gingival), and multifocal oral mucosa; one had a T2N0 oral tongue; and one had dysplasia. After excision, two were given radiation but recurred shortly thereafter; the others remain well and have had no further exposure to cytotoxic drugs, including PLD. Conclusion. Awareness of this possible long-term complication during PLD treatment should enhance the likelihood of early detection of oral lesions in these patients. Decisions to continue maintenance PLD after complete response of the original cancer should perhaps consider the benefits of delaying ovarian cancer recurrence versus the possible risk for a secondary cancer.

Outbreaks of Rift Valley fever (RVF) virus in Africa are characterized by distinct spatial and temporal patterns that are directly related to specific environmental parameters associated with mosquito vectors that function in the maintenance (endemic) and transmission (epizootic) cycles of the virus. National Oceanic and Atmospheric Administration (NOAA) satellites with limited resolution (1 km) can indirectly measure rainfall inexpensively over subcontinental or continental areas at a high temporal frequency, and identify regions with a high potential for viral activity. Within regions of likely viral activity, mosquito vector-breeding habitats (dambos) are identified and mapped with archived, high-quality, cloud-free, higher resolution data from LANDSAT (thematic mapper resolution 30 m) and SPOT (multispectral resolution 20 m) satellites. Active sensors, like airborne synthetic aperture radar systems (range resolution 1.6 m), are capable of detecting flooded habitats, even through cloud cover. By identifying flooded habitats within regions with a high likelihood of RVF activity, the potential source foci of an outbreak may be detected close to real-time and control efforts implemented prior to the start of a RVF epidemic/epizootic.

We present a methodology which uses a collection of workstations connected by an Ethernet network as a parallel processor for solving large-scale linear programming problems. On the largest problems we tested, linear and super-linear speedups have been achieved. Using the “branch-and-cut” approach of Hoffman, Padberg and Rinaldi, eight workstations connected in parallel solve problems from the test set documented in the Crowder, Johnson and Padberg 1983Operations Research article. Very inexpensive, networked workstations are now solving in minutes problems which were once considered not solvable in economically feasible times. In this peer-to-peer (as opposed to master-worker) implementation, interprocess communication was accomplished by using shared files and resource locks. Effective communication between processes was accomplished with a minimum of overhead (never more than 8% of total processing time). The implementation procedures and computational results will be presented.

The health of 155 former workers in a US military research program who had received multiple vaccines and 265 matched community controls was assessed. The study population was mostly male (83%) and elderly (median age, 69 years). Multiply immunized (MIP) subjects received vaccines and/or skin tests (median = 154) over a median of 17.3 years; interval from start of immunizations to survey completion was 15-55 years (mean = 43.1 years). MIP subjects characterized themselves as slightly less healthy than controls (P = 0.057). Fatigue (but no other symptom) was reported more frequently in the MIP group (P = 0.011), but was not associated with number of injections, number of vaccines, or time in program. No differences between MIP and control groups were seen for numerous self-reported medical conditions. Several statistically significant abnormalities were seen in clinical laboratory tests among MIP subjects, but none appeared to be clinically significant. A significant difference in frequency of monoclonal spikes and/or paraprotein peaks between MIP (12.5%) and control (4.5%) groups (RR = 2.7, P < 0.003) was observed; no associations with lifestyle, vaccine exposure, or medical conditions were found.

Bacillus anthracis is the major terrorist and biological warfare agent of concern to civilian and military medical planners. The licensed anthrax vaccine, adsorbed (AVA) is believed to be an effective prophylactic medical countermeasure against this threat. Our objective in this report was to expand the safety database for this vaccine by assessing data on self-reported, short-term safety of AVA during more than 25 years of use, measured by local and systemic adverse events temporally associated with the administration of AVA. A minority of AVA recipients reported systemic and injection site reactions. Females reported a higher incidence of injection site and systemic adverse events than males. Data show a difference in incidence of local reactions between lots. A prospective, randomized, placebo-controlled study to actively examine reactogenicity is needed to more completely define the extent and nature of reactions associated with receipt of AVA in humans as well as to confirm the gender lot differences in local reaction rates.

The influence of dosing interval on the human antibody response to anthrax vaccine adsorbed (AVA) was evaluated in two retrospective serological studies. In both studies, the interval between the first two doses was 2, 3 or 4 weeks. In the first study, banked sera were selected from 89 at-risk individuals at a mean time of 13 days after the second dose of vaccine. In the second study, banked sera were selected from 51 at-risk individuals at a mean time of 48 days following the first dose of AVA. In both studies, the geometric mean anti-protective antigen IgG antibody titer increased significantly as the interval between the two doses increased from 2 to 4 weeks (p=0.0005-0.029). In the first study, the seroconversion rate also increased as the interval between the first two doses increased (p=0. 0034). A prospective, randomized study has been completed and is being analyzed to confirm these findings.

5557 Background: Long-term maintenance therapy with PLD has been explored as a treatment for relapsed ovarian cancer (Andreopoulou et al. Ann Oncol 2007; 18:716-21). Our institution has monitored a...

The effect of Rift Valley fever (RVF) viral infection on the survival of female Culex pipiens was examined. In 3 experiments in which mosquitoes ingested RVF virus, there was a 44% decrease in survival to days 14-16 for transmitting vs. nontransmitting mosquitoes, and a 48% decrease in survival for individuals with disseminated vs. nondisseminated infections. These results were corroborated by other experiments in which survival of mosquitoes intrathoracically inoculated with RVF virus was compared with that of those inoculated with diluent. In both the per os and inoculation tests, uninfected mosquitoes survived significantly longer than infected mosquitoes. Even though mosquitoes with disseminated infections had a lower survival rate than did uninfected mosquitoes, dissemination and transmission rates were similar at days 7 and 14-18 after the infectious bloodmeal. This suggests that nondisseminated individuals were developing disseminated infections and becoming capable of transmitting virus between days 7 and 14-18 at approximately the same rate older transmitters were dying. The decreased survival associated with RVF viral infection should be considered in predictive models of this disease.