Clinical factors and association with treatment modalities in patients with breast cancer and brain metastases who develop leptomeningeal metastases.

PURPOSE: Leptomeningeal metastases (LM) are an aggressive complication of metastatic breast cancer (MBC) with brain metastases (BM), with a short survival of weeks to months. Studies suggest that surgical resection of BM may increase the risk of LM, especially in infratentorial metastases. In this retrospective study, we examine this and other factors which may be associated with increased risk of LM. METHODS: A database search at a single institution identified 178 patients with MBC and treated BM between 2007 and 2020. We collected demographic, clinical, radiographic, and other treatment data. LM was diagnosed by cerebrospinal fluid (CSF) cytology, neuroimaging, or both. Cox proportional hazards model was used. RESULTS: After a median follow-up of 8.5 months, 41 out of 178 patients (23%) with BM developed LM. Median time to develop LM was 130 days. Mean age was 51.3 years. The number and size of the BM, hemorrhagic/cystic lesions, progressive/stable systemic disease, and extracranial metastases sites other than liver did not pose a higher risk of LM. Infratentorial lesions (HR = 5.41) and liver metastases (HR = 2.28) had a higher risk of LM. Patients who had any surgery did not have a higher risk for LM (HR 1.13). The LM group had a worse overall survival as compared to the non-LM group. CONCLUSION: Among MBC patients with BM, infratentorial BM and visceral liver lesions increase the risk of LM, whereas local treatment modalities such as surgery and radiation do not. These data imply that local treatment strategy should not differ based on potential risk for LM.

Diffuse Cerebral Edema and Impending Herniation Complicating Hepatic Encephalopathy in Hereditary Hemorrhagic Telangiectasia.

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.

Case report: Efficacy and safety of regorafenib plus fluorouracil combination therapy in the treatment of refractory metastatic colorectal cancer.

Background: More than half of patients with colorectal cancer (CRC) present with metastatic disease or develop recurrent disease on first-line and second-line options. Treatment beyond the second line remains an area of unmet need for patients with progressive or recurrent disease. Methods: We retrospectively reviewed data of adult (>18 years old) patients with mCRC who received regorafenib + 5FU combination therapy at Houston Methodist Hospital with outcomes of interest including response rate, discontinuation due to side effects, and overall survival. Results: Seven patients received regorafenib + 5FU combination therapy for mCRC after receiving at least two other lines of therapy (including at least one fluorouracil-based therapy). Four patients (57%) achieved disease control in 7-12 weeks after therapy initiation while three patients developed recurrent disease. In patients who achieved disease control, no new adverse events were reported among patients with this combination. Conclusion: Regorafenib and Fluorouracil combination could be considered an option beyond the second line for patients with treatment-refractory metastatic colorectal cancer. Further studies, including a prospective trial, are needed to investigate the efficacy and safety of regorafenib plus 5FU therapy compared to other limited available therapies.

Pancreatic head vs pancreatic body/tail cancer: Are they different?

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.

Impact of Infections in Patients Receiving Pembrolizumab-Based Therapies for Non-Small Cell Lung Cancer.

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.

Consuming Genistein Improves Survival Rates in the Absence of Laxative in ΔF508-CF Female Mice.

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.