Faculty Bibliography

Background: Neoadjuvant chemoradiation (CRT) followed by surgical resection is a standard approach for patients (pts) with locally advanced esophageal/GEJ cancers. A pathologic complete response (pCR) is achieved in 22-23% of adenocarcinomas (AC) and 42-49% of squamous cell carcinomas (SCC) and is associated with improved survival outcomes. Sotigalimab (sotiga) is a high affinity, potent CD40 agonist mAb capable of inducing and expanding anti-tumor immune responses by activating dendritic cells (DCs), T cells, NK cells, B cells, and M1 macrophages. This study examined the safety and efficacy of combining sotiga with neoadjuvant CRT in pts with esophageal/GEJ cancers.
Method(s): Pts with resectable (T1-3, Nx) AC or SCC of the esophagus/GEJ were eligible. T1N0 and cervical tumors were excluded. Study treatment: carboplatin (AUC 2)/paclitaxel (PTX) (50 mg/m²) weekly x 5 with radiation 5040 cGy plus up to 4 doses of sotiga 0.3mg/kg IV prior to Ivor-Lewis esophagectomy. Primary efficacy endpoint was pCR.
Result(s): 34 pts were enrolled (safety pop). Histology: 76% AC, 24% SCC; clinical stage: II/III/IVA, 9%/68%/23%; location: GEJ 47%. AEs (> 20%) attributed to sotiga: nausea, chills, fatigue, cytokine release syndrome (CRS), pyrexia, vomiting, abnormal LFTs, thrombocytopenia, diarrhea, and pruritus; majority Grade 1-2. Grade >3 CRS was observed in 3 pts (9%). No pt withdrawals due to sotiga; no treatment-related deaths. 28 pts were evaluable for the primary endpoint (3 opted against surgery, 1 pt withdrew after PTX reaction, 1 unrelated death, 1 surgery still pending). Path responses: 10 pCR (36%), 16 pPR (57%), 18 major path resp (<10% residual tumor) (64%). 2 PD (7%), ORR 93%. pCR by histology: 7/23 AC (30%), 3/5 SC (60%). Post-tumor samples demonstrated increased infiltration and activation of DCs and monocytes compared to baseline.
Conclusion(s): Sotiga combined with neoadjuvant chemoradiation for esophageal/GEJ cancers was generally well tolerated and achieved pCR rates in both AC and SCC that compare favorably to historical data and are promising for this treatment strategy. Additional evaluations of clinical outcomes (including DFS, OS) and immune-based biomarkers are ongoing. Clinical trial identification: NCT03165994. Legal entity responsible for the study: Apexigen, Inc.
Funding(s): Apexigen, Inc. Disclosure: A.H. Ko: Financial Interests, Personal, Other, Member of Data Monitoring Committee: Imugene, Erytech, Roche/Genentech, Ipsen; Financial Interests, Personal, Other, Developed content for web-based platform as well as lecture materials on pancreatic cancer; speaker at multiple CME activities: Clinical Care Options; Financial Interests, Personal, Other, Member and now chair of Pancreatic Cancer Task Force: National Cancer Institute; Financial Interests, Institutional, Invited Speaker, Local PI for clinical trial (pancreatic cancer): Celgene, Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Local PI for clinical trial (esophageal cancer): Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, National PI for clinical trial (GI cancers): Abgenomics; Financial Interests, Institutional, Invited Speaker, National PI for clinical trial (esophageal cancer): Apexigen; Financial Interests, Institutional, Invited Speaker, Local PI for clinical trial (gastric cancer): Leap Therapeutics, Astellas; Non-Financial Interests, Other, MemberMultiple prior committee/speaking roles for Annual MeetingAssociate Editor: American Society of Clinical Oncology; Non-Financial Interests, Sponsor/Funding, For Precision Promise clinical trials consortium. Funding paid directly to my institution.: Pancreatic Cancer Action Network; Non-Financial Interests, Sponsor/Funding, For clinical trials collaboration. Funding paid directly to my institution.: Parker Institute for Cancer Immunotherapy. M. Noel: Financial Interests, Personal, Advisory Role: Celgene, Taiho Pharma, Ipsen; Financial Interests, Personal, Speaker's Bureau: Celgene, Taiho Pharma, Daiichi Sankyo/ AstraZeneca; Financial Interests, Institutional, Funding: Apexigen. J. Chao: Financial Interests, Personal, Advisory Role: Lilly, Merck, AstraZeneca, Daiichi Sankyo, Ono Pharma, Bristol Myers Squibb, Astellas Pharma, Turning Point Thera, Roche, Silverback Thera, Novartis, Coherus Biosciences, Geneos; Financial Interests, Personal, Advisory Role, +travel: Foundation Medicine, Macrogenics, Amgen; Financial Interests, Personal, Speaker's Bureau, +travel: Merck; Financial Interests, Personal, Speaker's Bureau: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Merck, Novonco Thera, Brooklyn Immunotherapeutics, Apexigen. D. Sohal: Financial Interests, Personal, Advisory Role: Perthera, Ability Pharma, AstraZeneca; Financial Interests, Personal, Speaker's Bureau: Incyte, Genentech; Financial Interests, Personal, Other, Honoraria: Foundation Medicine; Financial Interests, Institutional, Funding: Celgene, Genentech, Bristol-Myers Squibb, Incyte, Rafael Pharma, Apexigen, Amgen, Ability Pharma, AstraZeneca, FibroGen, Merck. M. Crow: Financial Interests, Personal, Funding: Merck, Incyte, Janssen; Financial Interests, Institutional, Funding: Apexigen. P.E. Oberstein: Financial Interests, Personal, Advisory Role, +travel: Merck; Financial Interests, Personal, Advisory Role: Rubius Thera, QED Thera, AstraZeneca, Delcath Systems; Financial Interests, Personal, Speaker's Bureau: AstraZeneca; Financial Interests, Personal, Expert Testimony: Ipsen; Financial Interests, Institutional, Funding: Merck, Roche/Genentech, Rafael Pharma, Arcus BioSciences. A. Scott: Financial Interests, Personal, Advisory Role, +travel: Exelixis, QED Pharma; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Stocks/Shares: Johnson johnson; Financial Interests, Personal, Funding: Exelixis, Genentech, Incyte, Five Prime, Merck; Financial Interests, Institutional, Funding: Apexigen. A. McRee: Financial Interests, Personal, Full or part-time Employment, recent move to industry: Janssen; Financial Interests, Personal, Stocks/Shares: Johnson Johnson; Financial Interests, Institutional, Funding: Inovio Pharma, Novartis, Merck, Boston Biomedical, AstraZeneca, Rgenix, BioMed Valley Discoveries, Takeda. C. Rocha Lima: Financial Interests, Personal, Funding: Rafael Pharma, Boston Biomedical, Pharmacyclics; Financial Interests, Institutional, Funding: Apexigen. L. Fong: Financial Interests, Personal, Stocks/Shares: Actym, Allector, Atreca, Bioatla, Bolt, Immunogenesis, Nutcracker, RAPT, Scribe, Senti, Soteria, TeneoBio; Financial Interests, Personal, Ownership Interest: Keyhole; Financial Interests, Institutional, Funding: Abbvie, Bavarian Nordic, Dendreon, Janssen, Merck, Roche/Genentech; Financial Interests, Personal and Institutional, Funding: BMS; Financial Interests, Institutional, Invited Speaker: Corvus; Financial Interests, Personal, Funding: AstraZeneca, Merck KGA. B. Keenan: Financial Interests, Institutional, Funding: Partner Therapeutics. E. Filbert: Financial Interests, Personal, Full or part-time Employment: Apexigen; Financial Interests, Personal, Stocks/Shares: Apexigen. F.J. Hsu: Financial Interests, Personal, Full or part-time Employment: Apexigen; Financial Interests, Personal, Officer: Apexigen. V. Shankaran: Financial Interests, Personal, Other, Honoraria: Cambia Health Foundatio; Financial Interests, Institutional, Funding: Amgen, Merck, Bayer, Bristol Myer Squibb, AstraZeneca, Genentech/Roche, Apexigen.
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OBJECTIVE:New York City (NYC) is home to the largest public healthcare system in the United States and was an early epicenter of coronavirus disease 2019 (COVID-19) infections. This system serves as the safety net for underserved and marginalized communities disproportionately affected by the pandemic. Prior studies reported substantial declines in pediatric emergency department (ED) volume during the initial pandemic surge, but few describe the ongoing impact of COVID-19 throughout the year. We evaluated the characteristics of pediatric ED visits to NYC public hospitals during the pandemic lockdown and reopening periods of 2020 compared to the prior year. METHODS:Retrospective cross-sectional analysis of pediatric ED visits from 11 NYC public hospitals from January 2019-December 2020. Visit demographics, throughput times, and diagnosis information during the early (3/7/20-6/7/20) and late (6/8/20-12/31/20) pandemic periods coinciding with the New York State of emergency declaration (3/7/20) and the first reopening date (6/7/20) were compared to similar time periods in 2019. Findings were correlated with key pandemic shutdown and reopening events. RESULTS:There was a 47% decrease in ED volume in 2020 compared to 2019 (125,649 versus 238,024 visits). After reopening orders began in June 2020, volumes increased but peaked at <60% of 2019 volumes. Admission rates, triage acuity, and risk of presenting with a serious medical illness were significantly higher in 2020 versus 2019 (P < 0.001). Time-to-provider times decreased however provider-to-disposition times increased during the pandemic (P < 0.001). Infectious and asthma diagnoses declined >70% during the pandemic in contrast to the year prior. After reopening periods began, penetrating traumatic injuries significantly increased compared to 2019 [+34%, Relative Risk: 3.2 (2.6, 3.8)]. CONCLUSIONS:NYC public hospitals experienced a sharp decrease in pediatric volume but an increase in patient acuity during both the initial pandemic surge and through the reopening periods. As COVID-19 variants emerge, the threat of the current pandemic expanding remains. Understanding its influence on pediatric ED utilization can optimize resource allocation and ensure equitable care for future surge events.

Objectives: Despite availability of new treatments, the prognosis of lung cancer remains poor. This study aims to provide recent estimates of survival in patients with advanced non-small cell lung cancer (NSCLC) in the US.
Method(s): The survival of patients with advanced NSCLC was estimated using two US databases together covering 2010-2020. The study included patients with stage III or IV NSCLC diagnosed between 2010-2016 in the Surveillance, Epidemiology, and End Results Program (SEER) database, and patients with stage IIIB, IIIC or IV NSCLC, diagnosed between 2017-2020, without known oncogenic driver mutations who had completed >=4 cycles of 1L treatment (restricted to platinum-based combinations, immuno-oncology monotherapy, or ipilimumab/nivolumab) in the Flatiron Health database, a US Oncology Electronic Medical Record database. Overall survival (OS) was defined as time from diagnosis of stage III or IV NSCLC to death or to date of last confirmed activity.
Result(s): A total of 49,298 and 133,395 patients with stage III and IV diagnosis respectively were identified in SEER. The 1-, 3- and 5-year OS for patients with Stage III disease were 55.1%, 26.3% and 17.5%, and for stage IV disease were 25.8%, 7.4% and 4.0%, respectively. The Flatiron database had 1,045 patients with stage IIIB, 130 patients with stage IIIC and 3,210 patients with stage IV disease at diagnosis. The 1- and 3-year OS for stage IIIB/IIIC disease were 72.5% and 36.4%, and for patients with stage IV disease were 65.9% and 24.6%, respectively.
Conclusion(s): Despite differences in study population characteristics between the two databases, the study shows that mortality in patients with advanced NSCLC remains high, underscoring the need for continued efforts to identify novel treatments and synergetic treatment combinations to improve patient outcomes.
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OBJECTIVE:Pneumococcal vaccination has decreased the bacteremia rate in both the general pediatric and sickle cell disease (SCD) populations. Despite this decrease, and an increasing concern for antibiotic resistance, it remains standard practice to obtain blood cultures and administer antibiotics in all febrile (>38.5°C) patients with SCD. We conducted a systematic review and meta-analysis of the available studies of the prevalence of bacteremia in febrile patients with SCD. METHODS:We searched the medical literature up to November 2018 in PUBMED, EMBASE, and Web of Science with terms epidemiology, prevalence, bacteremia, and sickle cell anemia. We only included studies with patients after 2000, when the pneumococcal 7-valent conjugate (PCV7) vaccine became widely available. The prevalence of bacteremia [95% confidence interval (CI)] was calculated by dividing the number of positive blood cultures by the number of febrile episodes. The I statistic measured heterogeneity between prevalence estimates. Bias in our studies was quantified by the Newcastle-Ottawa Quality Assessment Scale. RESULTS:Our search identified 228 citations with 10 studies meeting our inclusion/exclusion criteria. The weighted prevalence of bacteremia across all studies was 1.9% (95% CI, 1.22%-2.73%), and for Streptococcus pneumoniae bacteremia, it was 0.31% (95% CI, 0.16%-0.50%). Risks for bacteremia except central lines could not be determined because of the low prevalence of the outcome. CONCLUSIONS:There appears to be a need to develop a risk stratification strategy to guide physicians to manage febrile patients with SCD based on factors including, but not limited to, history and clinical examination, vaccination status, use of prophylactic antibiotics, laboratory values, likely source of infection, and accessibility to health care.

BACKGROUND:Protocols for diagnosing urinary tract infection (UTI) often use arbitrary cutoff values of urinalysis components to guide management. Interval likelihood ratios (ILRs) of urinalysis results may improve the test's precision in predicting UTIs. We calculated the ILR of urinalysis components to estimate the posttest probabilities of UTIs in young children. METHODS:Review of 2144 visits to the pediatric emergency department of an urban academic hospital from December 2011 to December 2019. Inclusion criteria were age <2 years and having a urinalysis and urine culture sent. ILR boundaries for hemoglobin, protein, and leukocyte esterase were "negative," "trace," "1+," "2+" and "3+." Nitrite was positive or negative. Red blood cells and white blood cells (WBCs) were 0 to 5, 5 to 10, 10 to 20, 20 to 50, 50 to 100, and 100 to 250. Bacteria counts ranged from negative to "loaded." ILRs for each component were calculated and posttest probabilities for UTI were estimated. RESULTS:(75.2%). The ILR for leukocyte esterase ranged from 0.20 (negative) to 37.68 (3+) and WBCs ranged from 0.24 (0-5 WBCs) to 47.50 (100-250 WBCs). The ILRs for nitrites were 0.76 (negative) and 25.35 (positive). The ILR for negative bacteria on urinalysis was 0.26 and 14.04 for many bacteria. CONCLUSIONS:The probability of UTI in young children significantly increases with 3+ leukocyte esterase, positive nitrite results, 20 to 50 or higher WBCs, and/or many or greater bacteria on urinalysis. The probability of UTI only marginally increases with trace or 1+ leukocyte esterase or 5 to 20 WBCs. Our findings can be used to more accurately predict the probability of true UTI in children.

Side effects from hormonal therapy (HT) for breast cancer treatment occur frequently and are associated with worse quality of life and HT non-adherence. Whether improved patient-physician communication is associated with patients' reporting of side effects is unknown. We undertook this study to assess factors associated with women's reports of HT side effects. Between December 2012 and April 2013, we conducted a cross-sectional survey of breast cancer patients undergoing HT in an urban medical center. Descriptive statistics, univariate analyses, and multivariate analyses were used to evaluate associations. Of the 100 participants, 67% reported having HT side effects. However, when prompted, an additional 9% reported experiencing specific HT-related symptoms. Despite very high communication scores, one-third of participants reported they had not discussed side effects with providers. Multivariate analysis showed that after controlling for age, education, race, and medication beliefs, women who had difficulty asking providers for more information were more likely to report side effects (odds ratio 8.27, 95% confidence interval 1.01-69.88). Although HT side effects often occur and are bothersome, patient-provider discussions about side effects remain suboptimal. Providers should actively ask patients about medication side effects so that they can be addressed to improve quality of life and potentially, medication adherence.

BACKGROUND:Immigrants from China and Africa have high rates of hepatitis B virus infection (HBV) and hepatocellular carcinoma (HCC); however, primary care physician (PCP) adherence to screening guidelines in at-risk communities is not well understood. METHODS:The New York City (NYC) neighborhood tabulation areas with the 25 greatest Chinese and African immigrant populations were determined based on US census data. The American Medical Association database was used to identify PCPs practicing in these neighborhoods. A Web-based survey designed to assess HBV and HCC knowledge and screening practices was distributed via e-mail to PCPs in these target areas. RESULTS:A total of 2072 physicians were contacted, and 109 responded to the survey, for a response rate of 5.3 %. Among responding physicians, 73 % report routinely testing immigrant patients for HBV. However, if a patient tests positive for HBV, only 68 % of providers recommend screening for HCC. Over a quarter of PCPs (27 %), failed to correctly state that antiviral therapy can lower the risk of developing HCC, and only 56 % correctly replied that screening for liver cancer improves survival. Of responders, only 54 % answered correctly that a 25-year-old patient from Africa with HBV should be screened for HCC, whereas 53 % answered incorrectly that a 25-year-old patient from China with HBV should be screened, demonstrating a lack of awareness of the different age of onset of liver cancer in the two groups. The most commonly reported barrier to offering both HBV testing and HCC screening was a "lack of clear guidelines." Neither HBV nor HCC was among the top 3 health concerns of patients, as perceived by their physicians. There were no significant differences between provider responses in Chinese and African immigrant neighborhoods. CONCLUSIONS:Providers serving Chinese and African immigrants in NYC often fail to recommend appropriate HBV and HCC screening. This appears to be due to significant gaps in provider knowledge and a lack of awareness of established screening guidelines. This study suggests the need for better distribution of existing guidelines to physicians serving immigrant-rich communities in order to improve HBV and HCC screening in high-risk individuals.