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Introduction: Targeting HRD with PARP inhibitors is now considered a standard treatment strategy in different tumor types. Whether HRD can be used as a tumor-agnostic predictive biomarker for PARP inhibition is not well established. Methods: A 43-year-old woman with no relevant past medical history or family history of cancer was diagnosed with metastatic uterine leiomyosarcoma with lung metastases in 2020. The patient started first line chemotherapy with doxorubicin achieving a partial response as best response and a duration of response of 5 months. Upon disease progression, the patient was initiated on second line pazopanib but required treatment discontinuation due to treatment-related heart failure with an ejection fraction of 40%. Patient was referred to the phase 1 clinical trials unit at Vail d Hebron University Hospital. Comprehensive genomic profiling was performed using a CLIA certified panel testing 447 genes. Molecular profiling showed a two-copy deletion of BRCA2. TMB of 4.562 mutations per megabase. Tumor was mismatch-repair proficient. Myriad myChoice HRD Plus showed BRCA2 deletion and a genomic instability score of 69 (threshold 42), supporting HRD. The patient was approached for an early phase clinical trial testing a treatment combination based on a PARP 1/2 inhibitor and temozolomide (TMZ). Results: Treatment was overall well tolerated with no grade 3 or 4 treatment-related toxicities. First CT scan 8 weeks from treatment initiation showed partial response (PR) with tumor shrinkage of the two target lesions located in the liver and mediastinum. Thirteen months after treatment initiation, this patient achieved a RECIST 1.1 complete response (CR) with disappearance of both target lesions, which has been sustained for over 24 months (Figure). Conclusion: The clinical case presented here, supports the potential clinical utility of HRD testing across tumor types. [ABSTRACT FROM AUTHOR]

In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ⩾5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ⩾5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other "objects" such as apoptotic CTC or CK fragments to guide the clinical management of these patients. [ABSTRACT FROM AUTHOR]