Over the past decade, immunotherapy has demonstrated an impressive improvement in treatment outcomes for multiple cancers. Following the landmark approvals for use of immune checkpoint inhibitors, new challenges emerged in various clinical settings. Not all tumor types harbor immunogenic characteristics capable of triggering responses. Similarly, many tumors’ immune microenvironment allows them to become evasive, leading to resistance and, thus, limiting the durability of responses. To overcome this limitation, new T-cell redirecting strategies such as bispecific T-cell engager (BiTE) have become attractive and promising immunotherapies. Our review provides a comprehensive perspective of the current evidence of BiTE therapies in solid tumors. Considering that immunotherapy has shown modest results in advanced prostate cancer to date, we review the biologic rationale and promising results of BiTE therapy in this clinical setting and discuss potential tumor-associated antigens that may be integrated into BiTE construct designs. Our review also aims to evaluate the advances of BiTE therapies in prostate cancer, illustrate the major obstacles and underlying limitations, and discuss directions for future research.

Background/Objectives: Sarcopenia is an emergent prognostic biomarker in clinical oncology. Albeit increasingly defined through skeletal muscle index (SMI) thresholding, the literature cut-offs fail to discern heterogeneous baseline muscularity across populations. This study assesses the prognostic impact of using cohort-specific SMI thresholds in a Portuguese metastatic non-small-cell lung cancer (mNSCLC) cohort. Methods: Retrospective study including mNSCLC patients treated between January 2017 and December 2022. ImageJ v1.54 g was used to assess cross-sectional CT imaging at the third lumbar vertebra (L3) and calculate L3SMI. Sarcopenia was defined both according to Prado et al. and L3SMI thresholds derived from receiver operating characteristic analysis. Overall survival (OS) was the primary endpoint. Secondary endpoints included first-line (1L) progression-free survival (PFS) and sarcopenia subgroup analysis regarding body mass index impact on OS. Results: The initial cohort included 197 patients. Mean age was 65 years (±11.31). Most tumors were adenocarcinomas (n = 165) and presented with metastasis (n = 154). SMI was evaluable in 184 patients: cohort-specific thresholds (<49.96 cm²/m² for men; <34.02 cm²/m² for women) yielded 46.74% sarcopenic patients (n = 86) versus 66.30% (n = 122) per the literature definition. Cohort-specific thresholds predicted both OS (12.75 versus 21.13 months, hazard ratio [HR] 1.654, p = 0.002) and PFS (7.92 versus 9.56 months, HR 1.503, p = 0.01). Among sarcopenic patients, overweight (HR 0.417, p = 0.01) and obesity (HR 2.723, p = 0.039) had contrasting impacts on OS. Conclusions: Amid reclassification of nearly one-fifth of the cohort, cohort-specific thresholds improved sarcopenia prognostication in mNSCLC. Homogeneity regarding both cancer treatment setting and ethnicity could be key to defining sarcopenia based on SMI.

Background/Objectives: Sarcopenia is an emergent prognostic biomarker in clinical oncology. Albeit increasingly defined through skeletal muscle index (SMI) thresholding, literature cut-offs fail to discern heterogeneous baseline muscularity across populations. This study assesses the prognostic impact of using cohort-specific SMI thresholds in a Portuguese metastatic non-small-cell lung cancer (mNSCLC) cohort. Methods: Retrospective study including mNSCLC patients treated between January 2017 and December 2022. ImageJ v1.54g was used to assess cross-sectional CT imaging at the third lumbar vertebra (L3) and calculate L3SMI. Sarcopenia was defined both according to Prado et al. and L3SMI thresholds derived from receiver operating characteristic analysis. Overall survival (OS) was the primary endpoint. Secondary endpoints included first-line (1L) progression-free survival (PFS) and sarcopenia subgroup analysis regarding body mass index impact on OS. Results: The initial cohort included 197 patients. Mean age was 65 years (± 11.31). Most tumors were adenocarcinomas (n = 165) and presented with metastasis (n = 154). SMI was evaluable in 184 patients: cohort-specific thresholds (< 49.96 cm2/m2 for men; < 34.02 cm2/m2 for women) yielded 46.74% sarcopenic patients (n = 86) versus 66.30% (n = 122) per the literature definition. Cohort-specific thresholds predicted both OS (12.75 versus 21.13 months, hazard ratio [HR] 1.654, p = 0.002) and PFS (7.92 versus 9.56 months, HR 1.503, p = 0.01). Conversely, Prado et al. definition lacked prognostic value. Among sarcopenic patients, overweight (HR 0.417, p = 0.01) and obesity (HR 2.723, p = 0.039) had contrasting impacts on OS. Conclusions: Amid reclassification of nearly one-fifth of the cohort, cohort-specific thresholds improved sarcopenia prognostication in mNSCLC. Homogeneity regarding both cancer treatment setting and ethnicity could be key to defining sarcopenia based on SMI.

Introduction Hepatocellular carcinoma (HCC) holds high cancer mortality worldwide. Immunotherapy-based combination therapy, currently the first-line (1L) standard of care in advanced HCC, has shifted the treatment paradigm concerning both efficacy and safety outcomes. Data on immune-related adverse events surrogacy for efficacy outcomes is mixed. Case Report We report the case of a 58-year-old male with chronic Hepatitis C virus infection who presented with a voluminous shoulder HCC metastasis. Albeit an initial significant biochemical response with 1L sorafenib, progressive disease after 3 months plus a bleeding complication led to treatment discontinuation. Second-line nivolumab, although yielding a rapid clinical and biochemical response, was permanently ceased after 12 weeks due to a grade 3 immune-related hepatitis. Notably, 5 years post-treatment, the patient sustains a major biochemical and radiographic response. Discussion This case highlights an unusual and sustained response to nivolumab treatment in HCC, following early treatment discontinuation due to severe hepatotoxicity.

Background: Since the identification of multiple therapeutic targets, as is the case of anaplastic lymphoma kinase (ALK) translocation, the paradigm of treating patients with non-small cell lung cancer (NSCLC) has improved. In order to guarantee the possibility of longer survival outcomes with a better quality of life we must invest in the determination, in suitable time, of the consensual biomarkers and in the availability of the best treatments to our patients. Case presentation: We present a case of a caucasian male in his fifth decade of life, non-smoker, who highlights the complex journey of ALK-positive patients. This particular case, demonstrates the efficacy and tolerability of the new ALK target therapies, allowing our patients to maintain their routines without compromising the effectiveness of the therapy. Conclusion: Focusing on the reality of ALK positive patients and the impact that this therapy has on the daily lives of our patients, we can contribute to the awareness of this specific pathology.

INPLASY202570053 Cognitive impairment in prostate cancer patients receiving androgen deprivation therapy: A scoping review Keywords: Prostate cancer; Androgen deprivation therapy; Luteinizing hormo…