Genistein is a naturally occurring isoflavone found in soy. Genistein has been shown to increase the open probability of the most common cystic fibrosis (CF) disease-associated mutation, ∆F508-CFTR. Mice homozygous for the ∆F508 mutation are characterized with severe intestinal disease and require constant laxative treatment for survival. This pathology mimics the intestinal obstruction (meconium ileus) seen in some cystic fibrosis patients. This study tested whether dietary supplementation with genistein would reduce the dependence of the ∆F508 CF mouse model on laxatives for survival, thereby improving mortality rates. At weaning (21 days), homozygous ∆F508 mice were maintained on one of three diet regimens for a period of up to 65 days: normal diet, normal diet plus colyte, or genistein diet. Survival rates for males were as follows: standard diet (38%, n = 21), standard diet plus colyte (83%, n = 42) and genistein diet (60%, n = 15). Survival rates for females were as follows: standard diet (47%, n = 19), standard diet plus colyte (71%, n = 38), and genistein diet (87%, n = 15). Average weight of male mice fed genistein diet increased by ~2.5 g more (p = 0.006) compared to those with colyte treatment. Genistein diet did not change final body weight of females. Expression of intestinal SGLT-1 increased 2-fold (p = 0.0005) with genistein diet in females (no change in males, p = 0.722). Expression of GLUT2 and GLUT5 was comparable between all diet groups. Genistein diet reduced the number of goblet cells per micrometer of crypt depth in female (p = 0.0483), yet was without effect in males (p = 0.7267). The results from this study demonstrate that supplementation of diet with genistein for ~45 days increases the survival rate of female ∆F508-CF mice (precluding the requirement for laxatives), and genistein only improves weight gain in males.

BACKGROUND The impact of pancreatic tumor location on patient survival has been studied in large national data-based analyses which yielded controversial results. AIM To explore if pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have different overall survival (OS), molecular signature and response to chemotherapy. METHODS We retrospectively queried patient records from July 2016 to June 2020 in our institution. Patient demographics, cancer stage on diagnosis, tumor location, somatic mutations, treatment, and survival are recorded and analyzed. A test is considered statistically significant if the P value was < 0.05. RESULTS We reviewed 101 patients with complete records, among which 67 (66.34%) were PHC and 34 (33.66%) were PBTC. More PHC were diagnosed at younger age [61.49 vs 68.97, P = 0.010], earlier stages ( P = 0.006) and underwent surgical resection ( P = 0.025). There were no significant differences among all mutations and pathways studied except for TP53 mutations (37.0% in PHC vs 70.0% in PBTC, P = 0.03). OS was not statistically different between PHC and PBTC ( P = 0.636) in the overall population and in subgroups according to surgical resection status or stages. In terms of response to chemotherapy, chemotherapy regimens (FOLFIRINOX-based vs gemcitabine-based) didn’t impact disease free interval in those who had surgical resection in either PHC ( P = 0.546) or PBTC ( P = 0.654), or the duration of response to first line palliative treatment in those with advanced disease in PHC ( P = 0.915) or PBTC ( P = 0.524). CONCLUSION Even though PHC and PBTC have similar poor OS and response to chemotherapy, the different presentations and molecular profiles indicate they are different diseases. Utilization of molecular profiling to develop targeted therapy for individualization of treatment is needed.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disease characterized by the formation of cutaneous and visceral telangiectasias and arteriovenous malformations (AVM). Multiple organs may be affected, including the nasal mucosa, skin, lungs, gastrointestinal tract, and brain. The following case highlights a unique manifestation of HHT in a patient with a gastrointestinal hemorrhage and epistaxis, resulting in hyperammonemia and diffuse cerebral edema and herniation. Clinicians should be aware of this potential complication in such patients and initiate ammonia-reducing agents early to avoid this devastating consequence.

Background: Immune checkpoint inhibitor (ICI) therapy has significantly improved outcomes across a range of malignancies. While infections are a well-known contributor to morbidity and mortality amongst patients receiving systemic chemotherapy regimens, little is known about the impact of infections on patients receiving ICI therapy. This study aims to assess incidence, risk factors, and outcomes in patients who develop infections while on pembrolizumab-based therapies for non-small cell lung cancer (NSCLC). Methods: Patients receiving pembrolizumab for stage III/IV NSCLC from 1/1/2017-8/1/2021 across seven hospitals were identified. Incidence and type of infection were characterized. Covariates including baseline demographics, treatment information, treatment toxicities, and immunosuppressive use were collected and compared between infected and non-infected patients. Outcomes included the rate of infections, all-cause hospital admissions, median number of treatment cycles, overall survival (OS), and progression free survival (PFS). Univariable and multivariable analysis with reported odds ratio (OR) and 95% confidence intervals (CI) were utilized to evaluate infection risks. OS and PFS were analyzed by Kaplan–Meier analysis and tested by log-rank test. p-value < 0.05 was considered statistically significant. Results: There were 243 NSCLC patients that met the inclusion criteria. Of these, 111 (45.7%) had one documented infection, and 36 (14.8%) had two or more. Compared to non-infected patients, infected patients had significantly more all-cause Emergency Department (ED) [37 (33.3%) vs. 26 (19.7%), p = 0.016], hospital [87 (78.4%) vs. 53 (40.1%), p < 0.001], and ICU visits [26 (23.4%) vs. 5 (3.8%), p < 0.001], and had poorer median OS (11.53 [95% CI 6.4–16.7] vs. 21.03 [95% CI: 14.7–24.2] months, p = 0.033). On multivariable analysis, anti-infective therapy (OR 3.32, [95% CI: 1.26–8.76], p = 0.015) and ECOG of >1 (OR 5.79, [95% CI 1.72–19.47], p = 0.005) at ICI initiation conferred an increased risk for infections. At last evaluation, 74 (66.7%) infected and 70 (53.0%) non-infected patients died (p = 0.041). Conclusion: Infections occurred in nearly half of patients receiving pembrolizumab-based therapies for NSCLC. Infected patients had frequent hospitalizations, treatment delays, and poorer survival. ECOG status and anti-infective use at ICI initiation conferred a higher infection risk. Infection prevention and control strategies are needed to ameliorate the risk for infections in patients receiving ICIs.

e21027 Background: The use of immune checkpoint inhibitors (ICI) based therapies, including in combination with platinum-based or as monotherapy, is currently the standard of care in stage IV NSCLC patients as a first line therapy. However, there is limited data on the options and outcomes of NSCLC patients if they progress after first-line therapy. This study aims to investigate the clinical outcomes to second lines of treatment for these patients. Methods: This is a retrospective study conducted at Houston Methodist Hospital involving adult patients (> 18 years old) with metastatic stage IV NSCLC who received ICI based therapy (combination or monotherapy) for the treatment of NSCLC and subsequently progressed or recurred and received a second line of therapy between 11/1/2016 and 12/31/2019. We excluded patients with targetable driver mutations (except KRAS) and patients with a concurrent cancer diagnosis. We collected information on the second line of therapy received and evaluated outcomes including progression-free survival (PFS), overall survival (OS) and overall response rate (ORR). PFS was defined from time of second-line therapy initiation to time of documented recurrence/progression. ORR was defined as patients who achieve partial response (PR) or complete response (CR). The Kaplan Meier method was used for survival analysis. Results: Among patients who received ICI-based first line therapy, 32 patients were identified to meet the inclusion criteria. Twenty-seven (84%) patients had adenocarcinoma and 17 patients had negative PD-L1 stain. Twenty-seven (84%) patients received a combination of carboplatin, pembrolizumab, and pemetrexed, whereas five (16%) patients received ICI monotherapy (3 pembrolizumab, 1 nivolumab and 1 durvalumab). Thirteen patients had an initial response to first-line therapy (11 PR, 2 CR). After progression/recurrence, various therapies were administered as second-line with the most common being the use of ICI + chemotherapy combination (6 pts, 19%) or ramucirumab + taxotere combination (6 pts, 19%). The remaining patients received other types of chemotherapy, targeted therapy, ICI, or were enrolled in a clinical trial. Nine patients (28%) had a response after 2nd line therapy [4 CR and 5 PR], 16 (50%) had progressive disease, and 5 (16%) had mixed response/stable disease. The cohort median PFS after 2nd line of therapy was 16.9 weeks (95% CI: 14.4-19.3). Conclusions: These findings reflect the variability in practices in stage IV NSCLC patients who progress after receiving ICI-based first line therapy. Outcomes of patients who progress after their first line remain suboptimal with short-lived responses. Further studies are needed to investigate the efficacy and safety of different second line treatment options.