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Long-term disease control in multiple myeloma (MM) is typically an unmet medical need, and most patients experience multiple relapses. Fluorescence in situ hybridization (FISH) is the standard technique to detect chromosomal abnormalities (CAs), which are important to estimate the prognosis of MM and the allocation of risk adapted therapies. In advanced stages, the importance of CAs needs further investigation. From 148 MM patients, two or more paired samples, at least one of which was collected at relapse, were analyzed by FISH. Using targeted next-generation sequencing, we molecularly investigated samples harboring relapse-associated CAs. Sixty-one percent of the patients showed a change in the cytogenetic profile during the disease course, including 10% who acquired high-risk cytogenetics. Amp(1q) (≥4 copies of 1q21), driven by an additional increase in copy number in patients who already had 3 copies of 1q21, was the most common acquired CA with 16% affected patients. Tetraploidy, found in 10% of the samples collected at the last time-point, was unstable over the course of the disease and was associated with TP53 lesions. Our results indicate that cytogenetic progression is common in relapsed patients. The relatively high frequency of amp(1q) suggests an active role for this CA in disease progression.

Circulating tumor DNA (ctDNA) represents a promising tool for diagnosis, prognosis and treatment monitoring of several malignancies. Its association with tumor burden in pancreatic ductal cancer (PDAC), especially in localized disease, is not fully explored yet. We aimed to investigate the association of pretherapeutic ctDNA levels in localized and metastatic PDAC with tumor volume and clinical outcomes.Liquid biopsy for ctDNA detection was prospectively obtained from patients with localized or disseminated PDAC prior to either resection or systemic treatment. Detection rates and levels of ctDNA (digital droplet PCR) were correlated to tumor volume, relapse rate and survival.60 patients with localized and 47 patients with metastatic PDAC were included. ctDNA was detected in 10% of localized and 57.4% of metastasized PDAC samples. In localized disease, ctDNA detection significantly correlated with the numbers of involved locoregional lymph nodes (p = 0.030). Primary tumor volume did not correlate with ctDNA levels in neither localized (p = 0.573) nor metastasized disease (p = 0.878). In disseminated disease, ctDNA levels correlated with total tumor volume (p = 0.026) and especially with liver metastases volume (p = 0.004), but not with other metastases. Detection of pretherapeutic ctDNA was associated with shorter DFS in localized (3.3 vs. 18.1 months, p = 0.000), whereas ctDNA levels were associated with worse survival in metastatic PDAC (5.7 vs. 7.8 months, p = 0.036).ctDNA positivity indicates major nodal involvement or even presence of undetected distant metastases associated with early recurrence in localized PDAC. Moreover, it predicts worse clinical outcome in both localized and metastatic disease.