A Systematised Literature Review of Real-World Treatment Patterns and Outcomes in Unresectable Advanced or Metastatic Biliary Tract Cancer
Bibliographic record
Abstract
BACKGROUND: Biliary tract cancers are rare aggressive malignancies typically diagnosed when the disease is metastatic or unresectable, precluding curative treatment. OBJECTIVE: We aimed to identify treatment guidelines, real-world treatment patterns, and outcomes for unresectable advanced or metastatic biliary tract cancers in adult patients. METHODS: Databases (MEDLINE, Embase, Cochrane Database of Systematic Reviews) were systematically searched between 1 January, 2000 and 25 November, 2021, and supplemented by hand searches. Eligible records were (1) treatment guidelines and (2) observational studies reporting real-world treatment outcomes, for unresectable advanced or metastatic biliary tract cancers. Only studies performed in the UK, Germany, France, Australia, Canada and South Korea were extracted, to moderate the number of records for synthesis while maintaining representation of a wide range of biliary tract cancer incidences. RESULTS: A total of 66 relevant unique full-text records were extracted, including 16 treatment guidelines and 50 observational studies. Among guidelines, chemotherapies were most strongly recommended at first line (1L); the combination of gemcitabine and cisplatin (GEMCIS) was recommended as the standard of care in 1L. Recommendations for systemic chemotherapy in the second line (2L) conflicted because of uncertainties around survival benefit. Guidelines on further lines of treatment included a range of locoregional modalities and stenting or best supportive care without providing clear recommendations because of data paucity. Fifty observational studies reporting real-world treatment outcomes were extracted, of which 25 (50%) and 9 (18%) reported outcomes in 1L and 2L, respectively; 22 (44%) reported outcomes for treatments described as 'palliative'. In 1L, outcomes for systemic chemotherapy were most frequently described (23/25 studies), and GEMCIS was the most common systemic chemotherapy used (10/23 studies) in line with guidelines. Median overall survival with 1L systemic chemotherapy was < 12 months in most studies (16/23; range 4.7-22.3 months). Most 2L studies (10/11) described outcomes for systemic chemotherapy, most commonly for fluoropyrimidine-based regimen (5/10 studies). Median overall survival with 2L systemic chemotherapy was < 12 months in 5/10 studies (range 4.9-21.5 months). Median progression-free survival was reported more rarely than median overall survival. Some studies with small sample sizes or specifically selected patient populations (e.g. higher performance status, or patients who had already responded to treatment) achieved higher median overall survival. CONCLUSIONS: At the time of this review, treatment options for unresectable advanced or metastatic biliary tract cancers confer poor real-world survival. For over a decade, GEMCIS remained the 1L standard of care, highlighting the lack of therapeutic innovation in this indication and the urgent unmet need for novel treatments with improved outcomes in this aggressive condition. Additional observational studies are needed to further understand the effectiveness of currently available treatments, as well as newly available therapies including the addition of immunotherapy in the evolving treatment landscape.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.021 | 0.105 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.005 |
| Bibliometrics | 0.050 | 0.048 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.004 | 0.005 |
| Open science | 0.002 | 0.003 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".