pancreatic-evidence

Pancreatic cancer grows and spreads quickly, and delays between the scan that finds it, the specialist meeting, the biopsy, the bile duct stent and the first chemotherapy or operation are measured in weeks. The proposal is a dedicated fast-track pathway with a national standard for the interval from first imaging to first treatment, reported by the audit.

The 2004 European trial that showed chemotherapy after pancreatic cancer surgery doubled five-year survival, while adding radiotherapy to the chemotherapy made survival worse, a result that split European and American practice for a decade.

The 2007 German and Austrian trial in which six months of gemcitabine after surgery roughly doubled the time before the cancer came back, making gemcitabine the standard after resection until 2017.

The 2018 Mayo Clinic study of 3,030 patients that found an inherited fault in one of six genes in 5.5 percent of all pancreatic cancers, including 5.2 percent of patients with no family history, which is why every patient is now offered a germline test.

Giving chemotherapy before the operation is standard when the tumour is borderline operable, but for tumours that can be removed straight away two trials have failed to show it beats operating first. Two more, one Dutch and one American, are directly comparing chemotherapy before and after surgery with chemotherapy after alone; the proposal is to wait for them and to pool them.

The 2024 Nature paper describing the chemistry behind daraxonrasib: a reversible drug that clamps the active form of every RAS protein, mutant or normal, and shrank tumours across RAS-driven models.

The 2014 mouse study showing that removing the scar-forming cells around pancreatic tumours made the cancers more aggressive and the mice die sooner, the warning that the stroma is not simply an obstacle to be cleared.

Most people with pancreatic cancer lose muscle and weight in a way food alone cannot reverse, and that wasting is a common reason chemotherapy is cut or stopped. A 2024 trial showed an antibody against the hormone GDF-15 restored weight and activity in twelve weeks, a third of the patients having pancreatic cancer. The proposal is to test it inside the chemotherapy trials, not alongside them.

A 2019 study of UK primary care records finding that only about one in five people with pancreatic cancer was prescribed the digestive enzyme capsules that replace what the diseased pancreas no longer makes, and that those who were lived markedly longer.

The 2021 update of the projection that pancreatic cancer will become the second leading cause of cancer death in the United States, now dated to 2040 with about 46,000 deaths a year, as deaths from breast, prostate and bowel cancer fall.

The 2022 five-year report of PRODIGE 24 confirming that modified FOLFIRINOX after pancreatic cancer surgery gives a median survival of about four and a half years against three with gemcitabine, and that 43 percent of patients were alive at five years.

The 2016 analysis of 456 pancreatic cancers that grouped 32 recurrently mutated genes into ten pathways and defined four expression subtypes, of which the squamous type has the worst prognosis.

The 2013 paper from Kevan Shokat's laboratory that found a hidden pocket on one mutant form of KRAS and made small molecules that bind it, ending the belief that the protein could not be drugged.

A 2021 study of stored blood from a US screening trial showing that CA 19-9 starts rising about two years before pancreatic cancer is diagnosed and catches half of early-stage cases in the final six months, so it can anchor a multi-marker early detection test.

The 2020 international consensus on who should have regular pancreatic scans because of family history or an inherited gene change, when to start, which scans to use and what the surveillance is trying to find.

The 2020 American guideline update that told doctors to test every treatment-eligible patient with metastatic pancreatic cancer for inherited BRCA changes, mismatch repair deficiency and TRK fusions, because each now had a drug attached.

The 2018 Mayo Clinic score, called ENDPAC, that uses weight change, blood sugar change and age at diabetes onset to pick out the new diabetics whose risk of pancreatic cancer is high enough to scan.

The 1988 paper that found a mutation in the KRAS gene in 21 of 22 pancreatic cancers, establishing the single most common driver in the disease and the target it took 33 more years to hit.

The 2016 trial that gave patients whose pancreatic cancer had grown through gemcitabine a proven second treatment: liposomal irinotecan with fluorouracil lengthened survival from about four to six months.

The 2025 Dutch trial in which eight cycles of FOLFIRINOX before surgery, with no treatment afterwards, gave the same survival (about 22 months) as the older gemcitabine chemoradiotherapy schedule, so either can be used but neither is clearly better.

The 2021 journal summary of the US NCCN pancreatic cancer guideline, focused on drug treatment for disease that has spread locally or to other organs.

The 2010 New England Journal review that summarised what was known about pancreatic cancer at the end of the gemcitabine era, a year before FOLFIRINOX changed treatment.

The European oncology society's 2023 guideline for pancreatic cancer, covering diagnosis, staging, surgery, chemotherapy before and after surgery, treatment of advanced disease and follow-up; the reference standard European and UK care is compared against.

The pancreas makes the enzymes that digest food, and a cancer in it, or the operation to remove it, leaves most patients unable to absorb what they eat. Capsules replacing those enzymes are cheap and recommended, yet UK records show only one patient in five was prescribed them. The proposal is to prescribe by default at diagnosis, publish each hospital's rate, and run the trial never done.

The 2024 phase 2 trial in which an antibody blocking the hormone GDF-15 helped patients with cancer-related wasting, a third of them with pancreatic cancer, gain about two to three kilograms in twelve weeks and become more active.

The 2019 American guideline update that made six months of modified FOLFIRINOX the preferred chemotherapy after pancreatic cancer surgery for patients fit enough to take it, on the strength of a single trial.

The 2020 primary report of the Dutch PREOPANC trial: giving chemotherapy and radiotherapy before surgery did not significantly lengthen survival overall, but it raised clear-margin resections from 40 to 71 percent and helped the patients whose tumours were borderline operable.

The 1978 report of two patients in whom the surgeons kept the stomach outlet intact during the Whipple operation, the modification most surgeons now use.

The 2005 Minnesota study that found about 1 in 100 people who develop diabetes after 50 is diagnosed with pancreatic cancer within three years, eight times the expected rate, which made new diabetes a possible early warning.

In England and Wales a national audit now reports each year what share of people diagnosed with pancreatic cancer receive any treatment aimed at the cancer, how many are discussed by a specialist team and how many see a specialist nurse. The proposal is a national target for the treatment rate, published by hospital, so the trusts furthest behind are visible.

The 2020 trial of an enzyme meant to dissolve the dense matrix around pancreatic tumours so chemotherapy could reach them: more tumours shrank, but patients lived no longer, and the drug was abandoned.

The first drug against the KRAS protein nearly doubled survival in pancreatic cancer in 2026, but on its own it holds the disease for months, not years. Trials are now testing it in combination with a second RAS drug and with chemotherapy, and earlier in the disease; the open questions are which combination, in which order, and what works when the tumour escapes.

The 1987 study showing that people who lack the Lewis blood group antigens cannot make the CA 19-9 tumour marker, so in about one patient in ten a normal blood test says nothing about the cancer.

Pancreatic tumours are mostly scar tissue. The first attempt to dissolve it, an enzyme given with chemotherapy to nearly 500 patients, shrank more tumours but did not lengthen life, and mouse work showed that stripping out the scar-forming cells made cancers worse. The proposal is to test drugs that change what the stroma does rather than remove it, in trials measured on survival.

The 2018 Johns Hopkins report of 354 people with inherited or family risk scanned for up to 16 years: 7 percent progressed to cancer or a high-grade precursor, 9 of the 10 cancers found by the scans were operable, and 85 percent of those patients were alive at three years.

The 2025 follow-up of the personalised mRNA vaccine trial in pancreatic cancer: at three years, patients whose immune systems responded to the vaccine had still mostly not relapsed, and the T cells the vaccine made were predicted to live for years.

About 1 in 100 people who develop diabetes after 50 has a pancreatic cancer behind it. A score built from weight change, blood sugar change and age, calculable from records already in primary care, picks out a group where the rate is nearer 1 in 30; the proposal is to scan that group rather than wait for symptoms.

One patient in twenty with pancreatic cancer carries an inherited gene fault, and most have no family history. Guidelines now say test every patient, which finds relatives who carry it too, but the yearly scans that catch cancer at stage I in carriers are still offered only in research programmes. The proposal is to make surveillance follow the test result automatically.

The 2022 report from eight US centres: among 1,461 people at high inherited risk under regular scanning, most pancreatic cancers were caught at stage I, and across all the CAPS cohorts patients whose cancer was found by surveillance lived a median of nearly ten years against a year and a half for those found outside it.

The 1935 report in which Allen Whipple and two colleagues described removing the head of the pancreas and the duodenum for cancer at the junction of the bile duct and bowel, the operation that still carries his name and remains the only route to cure.

The 2025 trial in which a wearable device delivering alternating electric fields to the abdomen, added to chemotherapy, lengthened survival in locally advanced pancreatic cancer from about 14 to 16 months and delayed the onset of pain.

The 2015 study that computationally separated cancer cells from the surrounding scar tissue in gene expression data and found two tumour types, classical and basal-like, and two kinds of stroma, each of which predicts survival.

The 2015 whole-genome study of 100 pancreatic cancers that sorted them by how broken their chromosomes were and noticed that the most unstable tumours, often with BRCA-type defects, responded to platinum chemotherapy.