A plain language summary of the results from the phase 2b HERIZON-BTC-01 study of zanidatamab in participants with HER2-amplified biliary tract cancer.

WHAT IS THIS SUMMARY ABOUT?: Researchers wanted to study whether the research drug zanidatamab could help people with a type of cancer called biliary tract cancer. In some people, biliary tract cancer cells make extra copies of a gene called HER2 (also called ERBB2). This is known as being HER2-amplified. Zanidatamab is an antibody designed to destroy cancer cells that have higher-than-normal HER2 protein or gene levels. Zanidatamab is currently under research and is not yet approved for any diseases. Participants in this phase 2b clinical study had tumors that were HER2-amplified and at the advanced or metastatic stage. Participants also had cancer which had become worse after previous chemotherapy or had side effects that were too bad to continue chemotherapy. They also had to meet other requirements to be enrolled. Researchers measured the amount of HER2 protein in the tumor samples of the participants who were enrolled. There were 80 participants with tumors that were both HER2 amplified and had higher-than-normal HER2 protein amounts (considered to be 'HER2-positive'). There were 7 participants with tumors that were HER2-amplified, but had little-to-no levels of the HER2 protein (considered to be 'HER2-low'). All participants in the study were treated with zanidatamab and no other cancer treatments once every 2 weeks. WHAT ARE THE KEY TAKEAWAYS?: In the HER2-positive group, 33 of 80 (41%) participants had their tumors shrink by 30% or more of their original size. In half of these participants, their tumors did not grow for 13 months or longer. No participant in the HER2-low group had their tumors shrink by 30% or more. In total, 63 of 87 participants (72%) had at least one side effect believed to be related to zanidatamab treatment. Most side effects were mild or moderate in severity. No participant died from complications related to zanidatamab. Diarrhea was one of the more common side effects and was experienced by 32 of 87 participants (37%). Side effects related to receiving zanidatamab through the vein, such as chills, fever, or high blood pressure, were experienced by 29 of 87 participants (33%). WHAT ARE THE CONCLUSIONS REPORTED BY THE RESEARCHERS?: The results of this study support the potential for zanidatamab as a new therapy for people with HER2-positive biliary tract cancer after they had already received chemotherapy. More research is occurring to support these results.Clinical Trial Registration: NCT04466891 (HERIZON-BTC-01 study).

The HERIZON-BTC-01 study revealed zanidatamab as a potentially effective treatment for HER2-positive biliary tract cancer after standard chemotherapy fails. Read more in the lay summary by @hardingjjmd, @DrShubhamPant, and coauthors. #BiliaryTractCancer #HER2 #zanidatamab.

Cholangiocarcinoma across England: Temporal changes in incidence, survival and routes to diagnosis by region and level of socioeconomic deprivation.

Background & Aims: While cholangiocarcinoma (CCA) incidence and mortality rates are increasing globally, whether there are regional/temporal variations in these rates for different biliary tract cancer (BTC) subtypes, or whether they differ by sex, socioeconomic status, or route to diagnosis (RtD) remains unknown. In this work, we aimed to perform an in-depth analysis of data on the incidence, mortality, survival and RtD of CCA and other BTCs. Methods: Data on all BTCs diagnosed in England between 2001 and 2018 were extracted from NHS Digital's National Cancer Registration Dataset. Age-standardised incidence rates (ASRs), mortality rates (ASMRs) and net survival rates were calculated, and Kaplan-Meier overall survival estimates and RtD trends were analysed. Analyses were stratified by sex, socioeconomic deprivation, tumour subtype and region. Results: The ASR for CCA rose from 2.9 in 2001-2003 to 4.6 in 2016-2018 and from 1.0 to 1.8 for gallbladder cancers (GBCs). ASMR trends mirror those of incidence, with most deaths due to iCCA. Over 20% of patients with CCA were under 65 years old. The ASRs and ASMRs were consistently higher in the most socioeconomically deprived group for CCA and GBC. The most common RtD was the emergency route (CCA 49.6%, GBC 46.2% and ampulla of Vater cancer 43.0%). The least deprived patients with CCA and ampulla of Vater cancer had better overall survival (p <0.001). Net survival rates rose for all BTCs, with 3-year net survival for CCA increasing from 9.2% in 2001 to 12.6% in 2016-2018. There was notable geographical variation in ASRs, ASMRs and net survival for all BTCs. Conclusions: BTC incidence and mortality rates are increasing, with differences observed between tumour types, socioeconomic deprivation groups, RtDs and geographical regions. This highlights the need for targeted interventions, earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals. Impact and implications: Cholangiocarcinoma (CCA) incidence and mortality rates are rising globally, particularly for intrahepatic CCA. However, it has not previously been reported if, within a single country, there are temporal and regional differences in incidence, mortality and survival rates for different biliary tract subtypes, and whether these differ by sex, socioeconomic status, or route of diagnosis. In this study we show that mortality rates for patients with CCA continue to rise and are almost 40% higher in the most socioeconomically deprived compared to the least; additionally, we observed regional variation within England in incidence, mortality and survival. This study is relevant to researchers and policy makers as it highlights regional variation and inequality, as well as emphasising the need for earlier diagnosis and better awareness of this condition amongst the public and healthcare professionals.

British Society of Gastroenterology guidelines for the diagnosis and management of cholangiocarcinoma.

These guidelines for the diagnosis and management of cholangiocarcinoma (CCA) were commissioned by the British Society of Gastroenterology liver section. The guideline writing committee included a multidisciplinary team of experts from various specialties involved in the management of CCA, as well as patient/public representatives from AMMF (the Cholangiocarcinoma Charity) and PSC Support. Quality of evidence is presented using the Appraisal of Guidelines for Research and Evaluation (AGREE II) format. The recommendations arising are to be used as guidance rather than as a strict protocol-based reference, as the management of patients with CCA is often complex and always requires individual patient-centred considerations.

Community Awareness and Education: In the West and Southeast Asia.

Although cholangiocarcinoma (CCA) or bile duct cancer is considered rare, worldwide it is the second most common primary liver cancer. The incidence is increasing globally, and mortality is high owing to its aggressiveness, late diagnosis, and refractory nature. In this chapter, the awareness of cholangiocarcinoma in the West and in Southeast Asia, particularly Thailand, is explored. The background to this cancer in each region is described, and the challenges faced by both by healthcare professionals and patients are uncovered. Although there is a growing number of organisations working at every level in each region to improve the situation for those with cholangiocarcinoma, there remains little awareness of the public health importance of this cancer. However, it is with health agencies and those at government level that hopes for an improved future for all those with cholangiocarcinoma must lie.

Regional variation in routes to diagnosis of cholangiocarcinoma in England from 2006 to 2017.

BACKGROUND: Incidence of cholangiocarcinoma (CCA) is rising, with overall prognosis re-maining very poor. Reasons for the high mortality of CCA include its late presentation in most patients, when curative options are no longer feasible, and poor response to systemic therapies for advanced disease. Late presentation presents a large barrier to improving outcomes and is often associated with diagnosis via mergency presentation (EP). Earlier diagnoses may be made by Two Week Wait (TWW) referrals through General practitioner (GP). We hypothesise that TWW referrals and EP routes to diagnosis differ across regions in England. AIM: To investigate routes to diagnosis of CCA over time, regional variation and influencing factors. METHODS: We linked patient records from the National Cancer Registration Dataset to Hospital Episode Statistics, Cancer Waiting Times and Cancer Screening Programme datasets to define routes to diagnosis and certain patient characteristics for patients diagnosed 2006-2017 in England. We used linear probability models to investigate geographic variation by assessing the proportions of patients diagnosed via TWW referral or EP across Cancer Alliances in England, adjusting for potential confounders. Correlation between the proportion of people diagnosed by TWW referral and EP was investigated with Spearman's correlation coefficient. RESULTS: Of 23632 patients diagnosed between 2006-2017 in England, the most common route to diagnosis was EP (49.6%). Non-TWW GP referrals accounted for 20.5% of diagnosis routes, 13.8% were diagnosed by TWW referral, and the remainder 16.2% were diagnosed via an 'other' or Unknown route. The proportion diagnosed via a TWW referral doubled between 2006-2017 rising from 9.9% to 19.8%, conversely EP diagnosis route declined, falling from 51.3% to 46.0%. Statistically significant variation in both the TWW referral and EP proportions was found across Cancer Alliances. Age, presence of comorbidity and underlying liver disease were independently associated with both a lower proportion of patients diagnosed via TWW referral, and a higher proportion diagnosed by EP after adjusting for other potential confounders. CONCLUSION: There is significant geographic and socio-demographic variation in routes to diagnosis of CCA in England. Knowledge sharing of best practice may improve diagnostic pathways and reduce unwarranted variation.

Cohort study to assess geographical variation in cholangiocarcinoma treatment in England.

BACKGROUND: Outcomes for cholangiocarcinoma (CCA) are extremely poor owing to the complexities in diagnosing and managing a rare disease with heterogenous sub-types. Beyond curative surgery, which is only an option for a minority of patients diagnosed at an early stage, few systemic therapy options are currently recommended to relieve symptoms and prolong life. Stent insertion to manage disease complications requires highly specialised expertise. Evidence is lacking as to how CCA patients are managed in a real-world setting and whether there is any variation in treatments received by CCA patients. AIM: To assess geographic variation in treatments received amongst CCA patients in England. METHODS: Data used in this cohort study were drawn from the National Cancer Registration Dataset (NCRD), Hospital Episode Statistics and the Systemic Anti-Cancer Therapy Dataset. A cohort of 8853 CCA patients diagnosed between 2014-2017 in the National Health Service in England was identified from the NCRD. Potentially curative surgery for all patients and systemic therapy and stent insertion for 7751 individuals who did not receive surgery were identified as three end-points of interest. Linear probability models assessed variation in each of the three treatment modalities according to Cancer Alliance of residence at diagnosis, and for socio-demographic and clinical characteristics at diagnosis. RESULTS: Of 8853 CCA patients, 1102 (12.4%) received potentially curative surgery. The mean [95% confidence interval (CI)] percentage-point difference from the population average ranged from -3.96 (-6.34 to -1.59)% to 3.77 (0.54 to 6.99)% across Cancer Alliances in England after adjustment for patient sociodemographic and clinical characteristics, showing statistically significant variation. Amongst 7751 who did not receive surgery, 1542 (19.9%) received systemic therapy, with mean [95%CI] percentage-point difference from the population average between -3.84 (-8.04 to 0.35)% to 9.28 (1.76 to 16.80)% across Cancer Alliances after adjustment, again showing the presence of statistically significant variation for some regions. Stent insertion was received by 2156 (27.8%), with mean [95%CI] percentage-point difference from the population average between -10.54 (-12.88 to -8.20)% to 13.64 (9.22 to 18.06)% across Cancer Alliances after adjustment, showing wide and statistically significant variation from the population average. Half of 8853 patients (n = 4468) received no treatment with either surgery, systemic therapy or stent insertion. CONCLUSION: Substantial regional variation in treatments received by CCA patients was observed in England. Such variation could be due to differences in case-mix, clinical practice or access to specialist expertise.

Italian clinical practice guidelines on cholangiocarcinoma Part I: classification, diagnosis and staging

Cholangiocarcinoma (CCA) is the second most common primary liver cancer, characterized by a poor prognosis and resistance to chemotherapeutics. The progressive increase in CCA incidence and mortality registered worldwide in the last two decades and the need to clarify various aspects of clinical management have prompted the Italian Association for the Study of the Liver (AISF) to commission the drafting of dedicated guidelines in collaboration with a group of Italian scientific societies. These guidelines have been formulated in accordance with the Italian National Institute of Health indications and developed by following the GRADE method and related advancements.

The multidisciplinary team meeting in the UK from the patients' perspective: comments and observations from cholangiocarcinoma patients and their families.

BACKGROUND: The multidisciplinary team (MDT) meeting has become the hallmark for cancer care in the UK. While standardizing care through adherence to guidelines, the MDT process can make the decision-making process somewhat remote from the patient perspective. The Cholangiocarcinoma Charity (AMMF) is the UK's only cholangiocarcinoma charity and is at the forefront of patient empowerment for those with this condition and for their families. It provides much needed support not only via personal contact but also through its website and on the social media platforms, Facebook and Twitter. METHODS: AMMF conducted a survey of patient attitudes to and experience of the MDT process through a simple questionnaire posted on Facebook in 2014. We report the results of the responses received, which we believe are worthy of further thought. FINDINGS: In the main, while treatment decisions are not queried, there is distress at the lack of involvement, the lack of representation, the lack of communication and at not knowing who to approach for answers to questions. CONCLUSION: This snapshot, although small, provides some insight to clinicians not to forget the constituency they serve, as communication is all important.