Peritoneal cell-free DNA as a sensitive biomarker for detection of peritoneal metastasis in colorectal cancer: a prospective diagnostic study: A prospective diagnostic study.

BACKGROUND: The detection of peritoneal metastasis (PM) is limited by current imaging tools. In this prospective study, we aimed to evaluate the sensitivity and specificity of peritoneal cell-free DNA (cfDNA) for diagnosis of PM. METHODS: Colorectal cancer (CRC) patients with/without PM were enrolled. The cfDNA experimental personnel and statists were blinded to the diagnosis of PM. Ultradeep sequencing covering large genomic regions (35000X, Next-generation sequencing) of cfDNA in peritoneal lavage fluid (FLD) and matched tumor tissues was performed. RESULTS: A total of 64 cases were recruited prospectively and 51 were enrolled into final analysis. In training cohort, 100% (17/17) PM patients obtained positive FLD cfDNA, comparing to 5/23 (21.7%) in patients without PM. Peritoneal cfDNA had a high sensitivity of 100% and specificity of 77.3% for diagnosis of PM (AUC: 0.95). In validation group of 11, 5/6 (83%) patients with PM obtained positive FLD cfDNA, comparing to 0/5 in non-PM (P = 0.031) with a sensitivity of 83.3% and specificity of 100%. Positive FLD cfDNA was associated with poor recurrence-free survival (P = 0.013) and was preceding radiographic evidence of recurrence. CONCLUSIONS: Peritoneal cfDNA is a promising sensitive biomarker for earlier detection of PM in CRC than current radiological tools. It can potentially guide selection for targeted therapies and serve as a surrogate instead of laparoscopic explore in the future. Trial Registration Chinese Clinical Trial Registry at chictr.org.cn (ChiCTR2000035400). URL: http://www.chictr.org.cn/showproj.aspx?proj=57626.

A Metastatic Cervical Adenocarcinoma Patient Carrying HER2 G292R Achieved Complete Response Upon Pyrotinib Treatment.

Cervical cancer patients who develop distant metastasis are rarely curable with very limited treatment options. Chemotherapy is often administered but with limited efficacy. Immunotherapy and anti-angiogenesis therapy are recommended for selected cases of recurrent or metastatic cervical cancers. The clinical efficacy of inhibitors targeting HER2, a commonly mutated gene in cervical cancer, has not been elucidated. Herein, we report a metastatic cervical adenocarcinoma patient carrying HER2 G292R who benefited from pyrotinib after progression on radio-chemotherapy, achieving complete response (CR) with a progression-free survival of 25 months and counting. Our study sheds light on the treatment options for previously treated metastatic cervical adenocarcinoma patients harboring activating HER2 mutations.

Two cases of non-small cell lung cancer patients with somatic or germline EGFR R776H mutation.

The development of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) has revolutionized the treatment for non-small cell lung cancer (NSCLC). Comprehensive genomic profiling for NSCLC enables clinicians to identify more uncommon genetic alterations in EGFR. It remains unclear whether patients with certain rare EGFR mutations can benefit from EGFR inhibitors. On the other hand, emerging evidence has also showed the involvement of inherited factors in lung cancer development. However, only few germline EGFR mutations have been reported, and their association with NSCLC familial risk remains ambiguous. Here, we report two cases of NSCLCs with uncommon EGFR mutation R776H. One patient carrying somatic EGFR R776H and L861Q was treated with afatinib and achieved a durable response. The other patient harbored a germline EGFR R776H and her son inherited the same germline R776H mutation whose CT examination showed multiple ground-glass nodules in both lungs requiring further follow-up and diagnosis. Our study demonstrated the responsiveness of compound R776H-L861Q mutations to afatinib. We also revealed the transmission of EGFR R776H and suggested it may confer the high susceptibility to lung cancer.