Deep diving in the PACIFIC:Practical issues in stage III non-small cell lung cancer to avoid shipwreck

After publication of the PACIFIC trial results,immune checkpoint inhibitor-based immunotherapy was included in the treatment algorithm of locally advanced non-small cell lung cancer(NSCLC).The PACIFIC trial demonstrated that 12 mo of durvalumab consolidation therapy after radical-intent platinum doublet chemotherapy with concomitant radiotherapy improved both progression-free survival and overall survival in patients with unresectable stage III NSCLC.This is the first treatment in decades to successfully improve survival in this clinical setting,with manageable toxicity and without deterioration in quality of life.The integration of durvalumab in the management of locally advanced NSCLC accentuates the need for multidisciplinary,coordinated decision-making among lung cancer specialists,bringing new challenges and controversies as well as important changes in clinical work routines.The aim of the present article is to review—from a practical,multidisciplinary perspective—the findings and implications of the PACIFIC trial.We evaluate the immunobiological basis of durvalumab as well as practical aspects related to programmed cell death ligand 1 determination.In addition,we comprehensively assess the efficacy and toxicity data from the PACIFIC trial and discuss the controversies and practical aspects of incorporating durvalumab into routine clinical practice.Finally,we discuss unresolved questions and future challenges.In short,the present document aims to provide clinicians with a practical guide for the application of the PACIFIC regimen in routine clinical practice.

Artificial intelligence and improved early detection for pancreatic cancer

Due mainly to a late stage at diagnosis and lack of effective treatment modalities,pancreatic cancer(PC)is a highly lethal malignancy with an overall 5-year survival rate of only 12%.1 Separating patients into those diagnosed with latestage disease with distant metastases and those diagnosed with localized tumors reveals a striking difference of 3%vs.44%5-year survival rates,respectively.Increasing the fraction of patients detected at an early stage,when PC is most likely to be curable,could therefore be of a major benefit.

scDPN for High-throughput Single-cell CNV Detection to Uncover Clonal Evolution During HCC Recurrence

Single-cell genomics provides substantial resources for dissecting cellular heterogeneity and cancer evolution.Unfortunately,classical DNA amplification-based methods have low throughput and introduce coverage bias during sample preamplification.We developed a single-cell DNA library preparation method without preamplification in nanolitre scale(scDPN)to address these issues.The method achieved a throughput of up to 1800 cells per run for copy number variation(CNV)detection.Also,our approach demonstrated a lower level of amplification bias and noise than the multiple displacement amplification(MDA)method and showed high sensitivity and accuracy for cell line and tumor tissue evaluation.We used this approach to profile the tumor clones in paired primary and relapsed tumor samples of hepatocellular carcinoma(HCC).We identified three clonal subpopulations with a multitude of aneuploid alterations across the genome.Furthermore,we observed that a minor clone of the primary tumor containing additional alterations in chromosomes 1q,10q,and 14q developed into the dominant clone in the recurrent tumor,indicating clonal selection during recurrence in HCC.Overall,this approach provides a comprehensive and scalable solution to understand genome heterogeneity and evolution.