Retrospective analysis of clinical characteristics and outcomes of patients with carcinoma of unknown primary from three tertiary centers in Australia.

BACKGROUND: Carcinoma of unknown primary (CUP) remains an important tumor entity and a disproportionate cause of cancer mortality. Little is known about the contemporary clinical characteristics, treatment patterns, and outcomes of CUP patients based on updated international classification guidelines. We evaluated a contemporary CUP cohort to provide insight into current clinical practice and the impact of tissue of origin assignment, site-specific and empirical therapy in a real-world setting. METHODS: We conducted a retrospective cohort study of CUP patients, as defined by the updated European Society of Medical Oncology (ESMO) 2023 guidelines, across three tertiary referral centers in Australia between 2015 and 2022. We analyzed clinical characteristics, treatment patterns, and survival outcomes using the Kaplan-Meier method and Cox regression proportional hazard model between favorable and unfavorable risk groups. RESULTS: We identified a total of 123 CUP patients (n = 86 unfavorable, n = 37 favorable risk as per the 2023 ESMO guidelines). Sixty-four patients (52%) were assigned a tissue of origin by the treating clinician. Median progression free survival (PFS) was 6.8 (95% confidence interval (CI) 5.1-12.1) months and overall survival (OS) 10.2 (95% CI 6.0-18.5) months. Unfavorable risk (hazard ratio [HR] 2.9, p = 0.006), poor performance status (HR 2.8, p < 0.001), and non-squamous histology (HR 2.5, p < 0.05) were associated with poor survival outcome. A total of 70 patients (57%) proceeded to systemic therapy. In patients with non-squamous histology and unfavorable risk, site-specific therapy compared to empirical chemotherapy did not improve outcome (median OS 8.2 vs. 11.8 months, p = 0.7). CONCLUSIONS: In this real-world cohort, CUP presentations were heterogenous. Overall survival and rates of systemic treatment were poor. Poor performance status and unfavorable risk were associated with worse survival. For most patients, site-specific therapy did not improve survival outcome. Improved and timely access to diagnostic tests and therapeutics for this group of patients is urgently required.

Clinical applications of mass spectrometry-based proteomics in cancer: Where are we?

Tumor tissue processing methodologies in combination with data-independent acquisition mass spectrometry (DIA-MS) have emerged that can comprehensively analyze the proteome of multiple tumor samples accurately and reproducibly. Increasing recognition and adoption of these technologies has resulted in a tranche of studies providing novel insights into cancer classification systems, functional tumor biology, cancer biomarkers, treatment response and drug targets. Despite this, with some limited exceptions, MS-based proteomics has not yet been implemented in routine cancer clinical practice. Here, we summarize the use of DIA-MS in studies that may pave the way for future clinical cancer applications, and highlight the role of alternative MS technologies and multi-omic strategies. We discuss limitations and challenges of studies in this field to date and propose steps for integrating proteomic data into the cancer clinic.