Plasma Growth Hormone as a Prognostic Biomarker to Durvalumab and Tremelimumab in Patients with Advanced Hepatocellular Carcinoma.

Introduction: In this study, we explored the potential of plasma growth hormone (GH) as a prognostic biomarker in patients with advanced HCC treated with durvalumab plus tremelimumab (D+T). Methods: In this study, we included 16 patients with advanced HCC who received D+T at MD Anderson Cancer Center between 2022 and 2023 and had plasma GH measurements recorded before treatment. Plasma GH levels were measured from prospectively collected blood samples and were correlated with progression-free survival (PFS) and overall survival (OS). The cutoff for normal GH levels in women and men was defined as ≤3.7 µg/L and ≤0.9 µg/L, respectively. The Kaplan-Meier method was employed to compute the median OS and PFS, while the Log rank test was applied to compare the survival outcomes between the GH-high and GH-low groups. Results: Sixteen patients were included in this analysis, two female and fourteen male, with a median age of 65.5 years. At the time of the analysis, the 6-month OS rate was 100% among GH-low patients (6 patients) and 30% among GH-high patients (10 patients). OS was significantly longer in GH-low patients (not evaluable) compared to GH-high patients (3.94 months) (p = 0.030). PFS was also significantly longer in GH-low patients (not evaluable) compared to the GH-high patients (1.87 months) (p = 0.036). Conclusion: Plasma GH is a prognostic biomarker in patients with advanced HCC treated with D+T. Given the relatively small patient cohort size, this finding should be further validated in larger randomized clinical trials in advanced HCC patients.

Mutational Signature Changes in Patients With Metastatic Squamous Cell Carcinoma of the Anal Canal.

PURPOSE: We examined the concordance of genetic mutations between pretreatment tumor tissue and posttreatment circulating tumor DNA (ctDNA) in patients with metastatic squamous cell carcinoma of the anal canal (SCCA) and assessed the impact of therapy on this concordance. METHODS: We analyzed next-generation sequencing reports from pretreatment tumor tissue and posttreatment ctDNA in 11 patients with metastatic SCCA treated at Vanderbilt University Medical Center between 2017 and 2021. RESULTS: Among the mutations identified in posttreatment ctDNA, 34.5% were also found in pretreatment tumor tissue, while 47.6% of pretreatment tumor tissue mutations were found in posttreatment ctDNA. Four patients had preservation of potentially actionable mutations in both pretreatment tissue and posttreatment ctDNA, while 7 patients had newly identified mutations in posttreatment ctDNA that were not present in pretreatment tumor tissue. CONCLUSION: Patients with SCCA demonstrate a high degree of temporal mutational heterogeneity. This supports the hypothesis that ctDNA can serve as a real-time tracking mechanism for solid tumors' molecular evolution in response to therapy. Our findings highlight the potential of ctDNA in identifying emerging actionable mutations, supplementing information from tissue-based genomic assessments. Further research, ideally with larger and multi-institutional cohorts, is needed to validate our findings in this relatively rare tumor type.

The Gut Microbiome as a Biomarker and Therapeutic Target in Hepatocellular Carcinoma.

The microbiome is pivotal in maintaining health and influencing disease by modulating essential inflammatory and immune responses. Hepatocellular carcinoma (HCC), ranking as the third most common cause of cancer-related fatalities globally, is influenced by the gut microbiome through bidirectional interactions between the gut and liver, as evidenced in both mouse models and human studies. Consequently, biomarkers based on gut microbiota represent promising non-invasive tools for the early detection of HCC. There is a growing body of evidence suggesting that the composition of the gut microbiota may play a role in the efficacy of immunotherapy in different types of cancer; thus, it could be used as a predictive biomarker. In this review, we will dissect the gut microbiome's role as a potential predictive and diagnostic marker in HCC and evaluate the latest progress in leveraging the gut microbiome as a novel therapeutic avenue for HCC patients, with a special emphasis on immunotherapy.

Cross-border utilization of cancer care by patients in the US and Mexico - a survey of Mexican oncologists.

BACKGROUND: The US-Mexico border is the busiest in the world, with millions of people crossing it daily. However, little is known about cross-border utilization of cancer care, or about the reasons driving it. We designed a cross sectional online survey to understand the type of care patients with cancer who live in the US and Mexico seek outside their home country, the reasons why patients traveled across the border to receive care, and the barriers faced when seeking cross-border care. RESULTS: The online survey was sent to the 248 cancer care providers working in the six Mexican border states who were registered members of the Mexican Society of Oncology. Responses were collected between September-November 2022. Sixty-six providers (response rate 26%) completed the survey. Fifty-nine (89%) reported interacting with US-based patients traveling to Mexico to receive various treatment modalities, with curative surgery (n = 38) and adjuvant chemotherapy (n = 31) being the most common. Forty-nine (74%) reported interacting with Mexico-based patients traveling to the US to receive various treatment modalities, with immunotherapy (n = 29) and curative surgery (n = 27) being the most common. The most frequently reported reason US-based patients sought care in Mexico was inadequate health insurance (n = 45). The most frequently reported reason Mexico-based patients sought care in the US was patients' perception of superior healthcare (n = 38). CONCLUSIONS: Most Mexican oncologists working along the Mexico-US border have interacted with patients seeking or receiving binational cancer care. The type of care sought, as well as the reasons for seeking it, differ between US and Mexico-based patients. These patterns of cross-border healthcare utilization highlight unmet needs for patients with cancer in both countries and call for policy changes to improve outcomes in border regions.

Molecular and genetic targets within metastatic colorectal cancer and associated novel treatment advancements.

Colorectal cancer results in the deaths of hundreds of thousands of patients worldwide each year, with incidence expected to rise over the next two decades. In the metastatic setting, cytotoxic therapy options remain limited, which is reflected in the meager improvement of patient survival rates. Therefore, focus has turned to the identification of the mutational composition inherent to colorectal cancers and development of therapeutic targeted agents. Herein, we review the most up to date systemic treatment strategies for metastatic colorectal cancer based on the actionable molecular alterations and genetic profiles of colorectal malignancies.

Systemic Neoadjuvant and Adjuvant Therapies in the Management of Hepatocellular Carcinoma-A Narrative Review.

The burden of hepatocellular carcinoma (HCC) continues to pose a significant global health problem. Several systemic therapies have recently been shown to improve survival for patients with unresectable disease. However, evidence to support the use of neoadjuvant or adjuvant systemic therapies in patients with resectable disease is limited, despite the high risk of recurrence. Neoadjuvant and adjuvant systemic therapies are being investigated for their potential to reduce recurrence after resection and improve overall survival. Our review identified various early-phase clinical trials showing impressive preliminary signals of pathologic complete response in resectable disease, and others suggesting that neoadjuvant therapies-particularly when combined with adjuvant strategies-may convert unresectable disease to resectable disease and cause significant tumor necrosis, potentially decreasing recurrence rates. The role of adjuvant therapies alone may also play a part in the management of these patients, particularly in reducing recurrence rates. Heterogeneity in trial design, therapies used, patient selection, and a scarcity of randomized phase III trials necessitate the cautious implementation of these treatment strategies. Future research is required to identify predictive biomarkers, optimize the timing and type of therapeutic combinations, and minimize treatment-related adverse effects, thereby personalizing and enhancing treatment strategies for patients with resectable and borderline resectable HCC.

Targeted therapies in advanced biliary tract cancers-a narrative review.

BACKGROUND AND OBJECTIVE: Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder cancer, are a relatively rare group of cancers with a poor prognosis. Over the past decade, the utilization of next-generation sequencing has led to the identification of multiple actionable somatic aberrations in BTCs. Subsequently, new therapies have been created to target these molecular alterations and have been incorporated into clinical practice. In this review, we outline therapies that have been previously studied, and those that are under investigation, to target genomic alterations with the goal of improving survival in patients with advanced disease. METHODS: A literature search was performed to identify phase I, II, and III trials of targeted therapies in patients with advanced BTCs published between January 1, 2010 and October 1, 2022. Medline (via PubMed) and ClinicalTrials.gov were searched for relevant studies and 415 trials were identified. The search strategy was performed using keywords including: biliary tract cancer, cholangiocarcinoma, gallbladder cancer, chemotherapy, targeted therapy, randomized trials, controlled trials, phase I, phase II, and phase III. Search results were imported into EndNote X 9.1. KEY CONTENT AND FINDINGS: Overall, immune checkpoint inhibitors, fibroblast growth factor receptor (FGFR) inhibitors, isocitrate dehydrogenase (IDH) inhibitors, and human epidermal growth factor receptor 2 (HER2)-directed therapies have all shown promising results with regard to efficacy in patients with advanced BTCs studied in clinical trials. A number of other agents have also been studied in early-phase trials. CONCLUSIONS: Targeted agents can improve survival in patients with advanced BTCs and have substantially increased the number of potential therapeutic options in patients with refractory disease. The therapeutic landscape of targeted therapies for patients with advanced BTCs continues to evolve based on improvements in detection of genomic alterations.

Variation in Treatment Patterns of Patients with Early-Onset Gastric Cancer.

Background: Early-onset gastric cancer (EOGC), or gastric cancer in patients younger than 45 years old, is poorly understood and relatively uncommon. Similar to other gastrointestinal malignancies, the incidence of EOGC is rising in Western countries. It is unclear which populations experience a disproportionate burden of EOGC and what factors influence how patients with EOGC are treated. Methods: We conducted a retrospective, population-based study of patients diagnosed with gastric cancer from 2004 to 2018 using the National Cancer Database (NCDB). In addition to identifying unique demographic characteristics of patients with EOGC, we evaluated (using multivariable logistic regression controlling for year of diagnoses, primary site, and stage) how gender/sex, race/ethnicity, treatment facility type, payor status, and location of residence influenced the receipt of surgery, chemotherapy, and radiation. Results: Compared to patients 45−70 and >70 years of age with gastric cancer, patients with EOGC were more likely to be female, Asian/Pacific Islander (PI), African American (AA), Hispanic, uninsured, and present with stage IV disease. On multivariable analysis, several differences among subsets of patients with EOGC were identified. Female patients with EOGC were less likely to receive surgery and chemotherapy than male patients with EOGC. Asian/Pacific Islander patients with EOGC were more likely to receive chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. African American patients were more likely to receive chemotherapy than Caucasian patients with EOGC. Hispanic patients were more likely to receive surgery and chemotherapy and less likely to receive radiation than Caucasian patients with EOGC. Patients with EOGC treated at community cancer centers were more likely to receive surgery and less likely to receive chemotherapy than patients with EOGC treated at academic centers. Uninsured patients with EOGC were more likely to receive surgery and less likely to receive chemotherapy than privately insured patients with EOGC. Patients with EOGC living in locations not adjacent to metropolitan areas were less likely to receive surgery compared to patients with EOGC who resided in metropolitan areas, Conclusions: Patients with EOGC are a demographically distinct population. Treatment of these patients varies significantly based on several demographic factors. Additional analysis is needed to elucidate why particular groups are more affected by EOGC and how treatment decisions are made for, and by, these patients.

Patterns of Colorectal Cancer in Texas Counties From 2000 to 2017.

PURPOSE: Residents living in Texas counties along the United States-Mexico border make up a unique demographic. These counties consist of a large proportion of Hispanic-Latinx people who experience a high rate of health uninsurance and underinsurance, low household income averages, and, as a whole, exhibiting relatively poor health outcomes compared to the US general population. Limited information exists regarding the effects of these characteristics on the incidence of colorectal cancer (CRC). METHODS: Using data from the Texas Department of State Health Service, we calculated that the overall age-adjusted incidence rate (AAIR) of CRC was lower and decreased at a slower rate over time in Texas border counties compared with nonborder counties in Texas. RESULTS: The AAIR of CRC was lower and decreased at a slower rate over time in Texas border counties compared with nonborder counties in Texas. Conversely to other groups analyzed, the AAIR of CRC in individuals age 50-64 years in border counties increased. CONCLUSION: These findings are likely a reflection of less utilization of cancer screening in border counties than in nonborder counties. The increase in AAIR of CRC among individuals age 50-64 years in border counties warrants further investigation.

Trends in the Incidence and Treatment of Early-Onset Pancreatic Cancer.

BACKGROUND: Early-onset pancreatic cancer (EOPC) is relatively uncommon. It is unclear if the incidence of EOPC is evolving and how these patients are treated. METHODS: We conducted a retrospective, population-based study using SEER 2004-2016. We evaluated annual age-adjusted incidence rate (AAIR), stage at presentation, and race/ethnicity among 7802 patients plus treatment patterns in 7307 patients (excluding neuroendocrine tumors) younger than 50. RESULTS: The AAIR was higher in males while the rate increased faster in females. The AAIR was highest in Non-Hispanic Black patients and increased for all races/ethnicities over time. The percentage of patients diagnosed with distant-stage disease decreased over time but increased for localized-stage disease. Hispanic patients made up a larger proportion of patients over time compared to other groups. For localized-stage disease, primary surgery alone was the most utilized modality of therapy. For regional-stage disease, chemotherapy with radiation was the most utilized modality from 2004-2010, whereas chemotherapy alone was the most utilized from 2011-2016. For distant-stage disease, chemotherapy alone was the most utilized and used increasingly over time. Patients with EOPC received radiation and chemotherapy at similar rates to, and underwent surgery more frequently, than patients 50-69. CONCLUSIONS: The AAIR of EOPC increased over time, faster so in females. Groups who experience a higher burden of pancreatic cancer, particularly African Americans, experienced a higher burden of EOPC. Treatment of localized and regional-stage disease did not follow standard treatment guidelines for pancreatic cancer. Our findings indicate that EOPC patients received more treatment than their older counterparts.

Surgical resection and survival outcomes in metastatic young adult colorectal cancer patients.

BACKGROUND: The incidence of colorectal cancer in adults younger than age 50 has increased with rates expected to continue to increase over the next decade. The objective of this study is to examine the survival benefit of surgical resection (primary and/or metastatic) versus palliative therapy in this patient population. METHODS: We identified 6708 young adults aged 18-45 years diagnosed with metastatic colorectal cancer (mCRC) from 2004 to 2015 from the SEER database. Overall survival (OS) was analyzed using Kaplan-Meier estimation, log rank test, and multivariate Cox proportional hazards model. RESULTS: Sixty-three percent of patients in our study underwent primary tumor resection (PTR), with 40% undergoing PTR alone and 23% undergoing both resection of primary disease and metastasectomy. The median OS for patients who underwent both PTR and metastasectomy was 36 months, compared to 13 months for those who did not receive any surgical intervention. The multivariate analysis showed significant OS benefit of receiving both PTR and metastasectomy (HR 0.34, 95% CI: 0.31-0.37, p < 0.001) compared to palliative therapy. Undergoing PTR only and metastasectomy only were also associated with improved OS (HR 0.46, 95% CI: 0.43-0.49, p < 0.001 and HR 0.64, 95% CI: 0.55-0.76, p < 0.001, respectively). CONCLUSION: This is the largest observational study to evaluate survival outcomes in young-onset mCRC patients and the role of surgical intervention of the primary and/or metastatic site. Our study provides evidence of statistically significant increase in OS for young mCRC patients who undergo surgical intervention of the primary and/or metastatic site.

Microbiome for Mars: surveying microbiome connections to healthcare with implications for long-duration human spaceflight, virtual workshop, July 13, 2020.

The inaugural "Microbiome for Mars" virtual workshop took place on July 13, 2020. This event assembled leaders in microbiome research and development to discuss their work and how it may relate to long-duration human space travel. The conference focused on surveying current microbiome research, future endeavors, and how this growing field could broadly impact human health and space exploration. This report summarizes each speaker's presentation in the order presented at the workshop.