COVID-19 and liver cancer: lost patients and larger tumours.

BACKGROUND: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region. OBJECTIVE: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region. DESIGN: We prospectively audited our service for the first year of the pandemic (March 2020-February 2021), comparing mode of presentation, disease stage, treatments and outcomes to a retrospective observational consecutive cohort immediately prepandemic (March 2019-February 2020). RESULTS: We observed a marked decrease in HCC referrals compared with previous years, falling from 190 confirmed new cases to 120 (37%). Symptomatic became the the most common mode of presentation, with fewer tumours detected by surveillance or incidentally (% surveillance/incidental/symptomatic; 34/42/24 prepandemic vs 27/33/40 in the pandemic, p=0.013). HCC tumour size was larger in the pandemic year (60±4.6 mm vs 48±2.6 mm, p=0.017), with a higher incidence of spontaneous tumour haemorrhage. The number of new cases of intrahepatic cholangiocarcinoma (ICC) fell only slightly, with symptomatic presentation typical. Patients received treatment appropriate for their cancer stage, with waiting times shorter for patients with HCC and unchanged for patients with ICC. Survival was associated with stage both before and during the pandemic. 9% acquired COVID-19 infection. CONCLUSION: The pandemic-associated reduction in referred patients in our region was attributed to the disruption of routine healthcare. For those referred, treatments and survival were appropriate for their stage at presentation. Non-referred or missing patients are expected to present with more advanced disease, with poorer outcomes. While protective measures are necessary during the pandemic, we recommend routine healthcare services continue, with patients encouraged to engage.

Emerging treatment options for ovarian cancer: focus on rucaparib.

Poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) are an exciting class of anticancer drugs, which have revolutionized the management of BRCA mutant/homologous recombination-deficient recurrent high-grade serous ovarian cancer (HGSOC). With three PARPi now approved by the US Food and Drug Administration, olaparib (Lynparza™), niraparib (Zejula™), and rucaparib (Rubraca™) in 2014 (and 2017 for the tablet formulation), 2016, and 2017, respectively, these drugs have now entered routine clinical practice. The marked single-agent efficacy of PARPi either as maintenance following response to platinum-based chemotherapy or as up-front treatment in these indications is based on the well-known concept of synthetic lethality. PARPi themselves work by blocking the repair of single-strand DNA breaks by the base excision/single-strand break repair pathway and can also be directly cytotoxic by the mechanism of PARP trapping. The greatest benefit in terms of progression-free survival, in all three PARPi maintenance registration studies, was seen in women with platinum-sensitive BRCA mutation-associated HGSOC. However, it is clear that non-BRCA HGSOC can benefit from PARPi and the ongoing challenge of biomarker driven studies is how best to define these patients. PARPi are well tolerated, but more information is needed to assess the longer-term/later onset toxicities as these agents are investigated in the first-line setting. The future direction and challenges for PARPi will be to continue to expand beyond BRCA and ovarian cancer by identifying molecular or functional signatures of response; to see if the durable responses in ovarian cancer can be improved and efficacy can be achieved in other cancer sub-types by combining with novel targeted agents. This review summarizes the development of PARPi as a class in ovarian cancer with particular focus on the PARPi rucaparib.