Meyer, Jeffrey

TPS611 Background: GPC3 is an oncofetal protein expressed in up to 75% of hepatocellular carcinomas (HCCs) and associated with poor prognosis. Its selective expression in tumor and not in normal tissue makes it a promising target for radiopharmaceutical imaging and therapy (theranostics). The GPC3-selective diagnostic RYZ811 ([ 68 Ga]Ga-RAYZ-8009) and therapeutic α particle-emitting RYZ801 ([ 225 Ac]Ac-RAYZ-8009) are a theranostic pair. Previous studies show high uptake of RYZ811 in intrahepatic and extrahepatic HCCs, with low normal liver background uptake. In GPC3+ HCC mouse models, single administrations of RYZ801 significantly inhibited tumor growth. Methods: RYZ801-101 is a single-arm, open-label, phase 1/1b study of RYZ811 and RYZ801 in previously treated patients with GPC3+ unresectable HCC. The study has two parts: dose escalation (part 1) and dose expansion (part 2). Each part consists of two stages: RYZ811 imaging and RYZ801 treatment. The aim of imaging is to determine if RYZ811 safely and adequately identifies patients with GPC3+ tumors. The aim of treatment is to determine the safety, pharmacokinetics (PK), recommended phase 2 dose (RP2D; part 1), and preliminary antitumor activity (part 2) of RYZ801. Key eligibility criteria are: confirmed HCC; Barcelona Clinic Liver Cancer stage B or C; Child-Pugh A; ≥1 RECIST v1.1-measurable lesion (treatment stage); and disease progression after ≥1 systemic therapy in part 1 and 1 prior line in part 2. In part 1, approximately 60 patients will receive RYZ811 (185 MBq) in the imaging stage; up to 30 of these will receive escalating doses of RYZ801 (2.6–5.5 MBq × 4 doses) in the treatment stage. In part 2, approximately 80 patients will receive RYZ811 (185 MBq) in the imaging stage; up to 40 of these will receive RYZ801 at the RP2D in the treatment stage. Primary RYZ811 objectives are to assess the safety/tolerability and biodistribution of RYZ811. Secondary objectives are to determine absorbed doses (ADs) to organs and tissues and any association between RYZ811 uptake and RYZ801 efficacy. Primary RYZ801 objectives are to identify the RP2D and safety/tolerability of RYZ801. Secondary objectives are to assess PK, ADs to critical organs and tumors, and preliminary antitumor activity. Enrollment for Part 1 is ongoing in the USA. Clinical trial information: NCT06726161 .

Abstract Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2–5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.

Purpose: Socioeconomic status (SES) influences health care outcomes, but the influence of primary payer on cancer-associated wasting is unknown. We hypothesized that primary payer as an indicator of SES would influence pretreatment cancer-associated weight loss and treatment outcomes. Materials and Methods: Retrospective review of medical records identified 1,366 patients with non–small-cell lung cancer (NSCLC) consecutively treated at a tertiary care health system between January 1, 2006 and December 31, 2013. Insurance status was obtained from an institutional tumor registry. Cancer-associated weight loss was based on the validated international consensus definition of cachexia. Multivariable regression analyses were used to identify prognostic factors of pretreatment cancer-associated weight loss and survival. Results: The cohort included a representative group of patients with a median age at diagnosis of 64 years, 47% females, and 33% patients of nonwhite race. Pretreatment cancer-associated weight loss was present at the time of NSCLC diagnosis in 17%, 14%, 32%, and 38% of patients with stage I, II, III, and IV disease, respectively. Pretreatment cancer-associated weight loss was associated with increasing age at diagnosis, black race, single marital status, tobacco use, and disease stage. Compared with private insurance, Medicaid insurance (odds ratio, 2.17; 95% CI, 1.42 to 3.30) and lack of insurance (odds ratio, 2.32; 95% CI, 1.50 to 3.58) were associated with pretreatment cancer-associated weight loss. Among cachectic patients, comorbidity, histology, tumor grade, and disease stage were prognostic of survival on multivariable analysis; however, primary payer was not. Conclusion: Pretreatment cancer-associated weight loss is common in patients with NSCLC, and its presence is significantly associated with lower SES. However, among patients with pretreatment cancer-associated weight loss, SES was not predictive of survival. Early use of cancer cachexia–directed therapies may improve outcomes, and further study on the biologic mechanisms of cancer cachexia will provide novel therapeutic avenues.

Purpose: Cancer-associated weight loss is associated with poor prognosis in advanced malignancy; however, its pretreatment prevalence and survival impact are inadequately described in large cohorts. Such data, stratified by tumor type and stage, may facilitate the optimal and timely allocation of complementary care, leading to improvements in patient survival and quality of life. Methods: We performed a retrospective cohort study of 3,180 consecutively treated adult patients with lung or GI (including colorectal, liver, and pancreatic) cancer. Pretreatment cancer-associated weight loss was based on the international consensus definition of cachexia. Prevalence and survival impact of pretreatment cancer-associated weight loss were evaluated using the Kaplan-Meier method and compared using log-rank test. Results: Cancer-associated weight loss was observed at the time of cancer diagnosis in 34.1% of patients. Pretreatment weight loss was documented in 17.6%, 25.8%, 36.6%, and 43.3% of stage I, II, III, and IV cancers, respectively. Wasting was common regardless of tumor type, with prevalence at diagnosis ranging from 27.3% in patients with colorectal cancer to 53.4% in patients with gastroesophageal cancer. Pretreatment weight loss was associated with reduced overall survival after adjusting for stage, size, grade, comorbidity, age, sex, and tobacco history (hazard ratio, 1.26; 95% CI, 1.13 to 1.39). Conclusion: Pretreatment cancer-associated weight loss is common, even in early-stage disease, and is independently associated with reduced survival. Minimal weight loss represents a clinically distinct entity with an associated overall survival intermediate to that of no weight loss and overt wasting. Early diagnosis and treatment of cancer-associated wasting offers a novel therapeutic avenue for reducing cancer mortality.

101 Background: Socioeconomic status (SES) influences healthcare outcomes, but the influence of SES on cancer cachexia is unknown. We identify components of SES associated with pre-treatment cachexia in patients with non-small cell lung cancer (NSCLC) and assess their prognostic significance on survival. Methods: A prospectively maintained institutional tumor registry identified 1,365 patients with NSCLC consecutively treated at a tertiary care health system from 1/1/06 to 12/31/13. Insurance status was abstracted from the registry. Educational attainment and household income were estimated from census data using location of primary residence. Cancer cachexia was defined retrospectively using the international consensus definition. Multivariable regression analysis was used to identify prognostic factors of pre-treatment cancer cachexia and survival. Results: Cachexia was present at the time of NSCLC diagnosis in 30% of all patients including 17% of patients with stage I disease. Patients with Medicaid or no insurance were more likely to have pre-treatment cachexia compared to those with private insurance (Odds Ratio [OR] 1.9, 95% Confidence Interval [CI] 1.2-3.1; OR 2.1, 95% CI 1.2-3.4, respectively). Attainment of a high school diploma was inversely associated with pre-treatment cachexia (OR: 0.1, 95% CI 0.02-0.2). On multivariable analysis, comorbidity, histology, tumor grade, and disease stage were prognostic of survival among cachectic patients; however, insurance status, educational attainment, and household income were not. Conclusions: Lower SES is associated with pre-treatment cachexia in patients with NSCLC, but pre-treatment cachexia is detrimental to survival regardless of SES. Together, these findings suggest early intervention for patients with cancer cachexia may improve outcomes.

AbstractThe Metastatic Spine Disease Multidisciplinary Working Group consists of medical and radiation oncologists, surgeons, and interventional radiologists from multiple comprehensive cancer centers who have developed evidence- and expert opinion-based algorithms for managing metastatic spine disease. The purpose of these algorithms is to facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding the use of available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation. This consensus document details the evidence supporting the Working Group algorithms and includes illustrative cases to demonstrate how the algorithms may be applied.Implications for Practice:The Metastatic Spine Disease Multidisciplinary Working Group algorithms can facilitate interdisciplinary referrals by providing physicians with straightforward recommendations regarding available treatment options, including emerging modalities such as stereotactic body radiation therapy and percutaneous tumor ablation.