{"id":"nutrition-lifestyle-roadmap","name":"Diet, exercise and lifestyle roadmap: causes established → interventions that disappointed → exercise proven as treatment","route":"/roadmaps/nutrition-lifestyle-roadmap/","eras":[{"era":"1950s-2016","title":"The causes are established","description":"Cohort studies and IARC's monographs built the list that is no longer in dispute: tobacco, alcohol (a group 1 carcinogen for at least seven cancers), processed meat, and excess body fat, which IARC linked to thirteen cancers in 2016. Physical inactivity and sugary drinks joined through the same evidence. The World Cancer Research Fund's Continuous Update Project keeps the grading current, which is why this front can say 'convincing', 'probable' or 'insufficient' rather than 'linked to'.","status":"historic","refs":[{"id":"risk-factor","kind":"term","name":"Risk factor","route":"/terms/risk-factor/","tldr":"Anything that raises the chance of developing a cancer: smoking, alcohol, obesity, sunlight, certain infections, inherited genes, age. Around 40% of cancers in high-income countries are attributable to modifiable factors, so having a risk factor does not mean getting cancer, and the majority of cancers cannot be pinned on a modifiable one."},{"id":"obesity-related-cancers","kind":"term","name":"Obesity-related cancers (IARC list of 13)","route":"/terms/obesity-related-cancers/","tldr":"Excess body fat is an established cause of thirteen cancers on the IARC list, including womb, oesophagus, kidney, liver, bowel, pancreas and postmenopausal breast cancer. It accounts for roughly 4 to 8% of cancers in high-income countries, second only to smoking among preventable causes, and bariatric surgery cohorts suggest the risk is partly reversible."},{"id":"alcohol-reduction-labelling","kind":"technology","name":"Alcohol reduction, pricing and cancer warning labels","route":"/technologies/alcohol-reduction-labelling/","status":"established","tldr":"Alcohol causes at least seven cancers and there is no safe threshold. Price, availability and cancer warning labels are the tools that work; most people still do not know alcohol causes cancer."},{"id":"red-processed-meat-reduction","kind":"technology","name":"Red and processed meat reduction","route":"/technologies/red-processed-meat-reduction/","status":"established","tldr":"Processed meat (bacon, ham, sausages) is classed by IARC as a definite cause of bowel cancer and red meat as a probable one, with about 18% higher risk per 50 g of processed meat a day. One person's extra lifetime risk is a few percentage points, but 5 to 10% of bowel cancers in high-income countries are attributed to it."},{"id":"ultra-processed-food-ssb","kind":"technology","name":"Ultra-processed food and sugar-sweetened drinks","route":"/technologies/ultra-processed-food-ssb/","status":"emerging","tldr":"Diets high in industrially processed foods and sugary drinks are linked with more cancer, mainly through obesity but perhaps also through additives and packaging chemicals. Sugar itself does not 'feed' a tumour in the way social media claims."},{"id":"metabolic-syndrome","kind":"term","name":"Metabolic syndrome and insulin resistance","route":"/terms/metabolic-syndrome/","tldr":"Metabolic syndrome is a cluster of central obesity, high blood pressure, high blood sugar and abnormal blood fats. It raises the risk of several cancers and worsens outcomes after diagnosis, largely through high insulin levels."},{"id":"iarc","kind":"institution","name":"International Agency for Research on Cancer (IARC / WHO)","route":"/institutions/iarc/","tldr":"IARC is the WHO's cancer agency, responsible for global cancer statistics (GLOBOCAN), carcinogen classification, and prevention research."},{"id":"dietary-pattern-scores","kind":"term","name":"Dietary pattern scores (Mediterranean, HEI, AHEI, DASH, WCRF/AICR)","route":"/terms/dietary-pattern-scores/","tldr":"Scores that grade a whole diet against a healthy pattern instead of counting single foods. They predict cancer risk and survival better than any individual nutrient."}],"trials":[],"papers":[]},{"era":"1990s-2020","title":"The intervention trials that disappointed, and taught","description":"Three thousand breast cancer survivors coached for years to eat far more vegetables had no fewer recurrences (WHEL). Vitamin D and fish oil did not prevent cancer in 25,000 people (VITAL). Fish oil did not slow cancer wasting. High-dose vitamin C failed twice in randomised trials at the Mayo Clinic. Each null result closed a question that supplements marketing keeps open, and together they set the standard: a diet claim needs a randomised trial with a cancer endpoint.","status":"historic","refs":[{"id":"whel","kind":"trial","name":"WHEL (Women's Healthy Eating and Living)","route":"/trials/whel/","status":"negative","tldr":"Three thousand breast cancer survivors were coached for years to eat far more vegetables, fruit and fibre. They did, and it made no difference to recurrence or survival."},{"id":"vital","kind":"trial","name":"VITAL (VITamin D and OmegA-3 TriaL)","route":"/trials/vital/","status":"negative","tldr":"The definitive test of whether vitamin D or fish-oil pills prevent cancer or heart disease in healthy adults. They did not."},{"id":"vitamin-d-omega3-supplementation","kind":"technology","name":"Vitamin D and omega-3 supplementation","route":"/technologies/vitamin-d-omega3-supplementation/","status":"phase-3","tldr":"The largest trial of vitamin D and fish-oil pills found they did not prevent cancer. A possible reduction in cancer deaths, and hints of benefit after a digestive cancer diagnosis, keep the question alive."},{"id":"omega3-epa-cachexia","kind":"technology","name":"Fish oil (EPA) for cancer weight loss","route":"/technologies/omega3-epa-cachexia/","status":"phase-2","tldr":"Fish oil rich in EPA was expected to slow cancer-related muscle wasting by damping inflammation. Randomised trials and a Cochrane review found no convincing effect on weight or survival, though fish oil is safe and sits comfortably inside general nutritional support."},{"id":"high-dose-vitamin-c","kind":"technology","name":"High-dose intravenous vitamin C","route":"/technologies/high-dose-vitamin-c/","status":"phase-2","tldr":"Vitamin C tablets do not treat cancer: two randomised trials at the Mayo Clinic settled that in the 1980s. Intravenous doses reach blood levels high enough to generate hydrogen peroxide in tumours, and small trials alongside chemotherapy are under way, but no adequately sized trial has yet shown benefit."},{"id":"dietary-supplements-treatment-interactions","kind":"technology","name":"Dietary supplements during cancer treatment: interactions and harms","route":"/technologies/dietary-supplements-treatment-interactions/","status":"established","tldr":"Most people on cancer treatment take supplements, often without telling their team. Antioxidants, St John's wort, high-dose vitamins and some herbs can blunt chemotherapy or radiotherapy or interact with targeted drugs."},{"id":"unproven-diet-claims","kind":"term","name":"Unproven diet claims (alkaline, juice, 'anti-cancer' diets)","route":"/terms/unproven-diet-claims/","tldr":"Diets marketed as cancer cures or preventives with no supporting evidence: alkaline diets, juice cleanses, Gerson therapy, apricot kernels and the like. Some are merely useless; several have caused harm or led people to delay effective treatment."},{"id":"warburg-effect-diet-claims","kind":"term","name":"Warburg-effect diet claims ('sugar feeds cancer')","route":"/terms/warburg-effect-diet-claims/","tldr":"Cancer cells take up far more glucose than normal tissue (the Warburg effect, the basis of FDG-PET scans), which leads people to conclude that cutting sugar starves tumours. The biology is real but the conclusion is not: blood glucose is tightly regulated, tumours also burn glutamine, lactate and fat, and no randomised trial shows sugar restriction improves cancer outcomes."}],"trials":[{"id":"whel","name":"WHEL (Women's Healthy Eating and Living)","route":"/trials/whel/","outcomes":[{"endpoint":"Invasive breast cancer event (recurrence or new primary)","primary":true,"unit":"%","arms":[{"name":"Dietary intervention","n":1537,"value":16.7},{"name":"Comparison","n":1551,"value":16.9}],"hr":0.96,"ci":[0.8,1.14],"source":"https://doi.org/10.1001/jama.298.3.289"}],"setting":"Early-stage breast cancer survivors within 4 years of diagnosis: intensive telephone counselling for a diet very high in vegetables, fruit and fibre and low in fat vs printed dietary guidelines","enrolled":3088,"enrolledBasis":"registry"},{"id":"vital","name":"VITAL (VITamin D and OmegA-3 TriaL)","route":"/trials/vital/","outcomes":[{"endpoint":"Invasive cancer of any type","primary":true,"unit":"events","arms":[{"name":"Vitamin D3","n":12927,"value":793},{"name":"Placebo","n":12944,"value":824}],"hr":0.96,"ci":[0.88,1.06],"p":"0.47","source":"https://doi.org/10.1056/NEJMoa1809944"},{"endpoint":"Invasive cancer of any type","primary":true,"unit":"events","arms":[{"name":"Omega-3","n":12933,"value":820},{"name":"Placebo","n":12938,"value":797}],"hr":1.03,"ci":[0.93,1.13],"source":"https://doi.org/10.1056/NEJMoa1809946"}],"setting":"Primary prevention in US adults (men 50+, women 55+) without prior cancer or cardiovascular disease: vitamin D3 2000 IU/day and/or marine omega-3 1 g/day vs placebo, 2x2 factorial","enrolled":25871,"enrolledBasis":"registry"}],"papers":[]},{"era":"2020-2026","title":"Exercise becomes a treatment","description":"CHALLENGE randomised nearly 900 people after colon cancer treatment to a three-year coached exercise programme or health education and, in 2025, reported fewer recurrences and fewer deaths in the exercise arm: the first randomised proof that a lifestyle intervention changes a hard cancer outcome. Exercise during chemotherapy is safe and reduces fatigue; four weeks of prehabilitation before major surgery cuts complications (PREHAB); enhanced recovery protocols replaced pre-operative fasting. The question is no longer whether but how to prescribe, deliver and pay for it.","status":"current","refs":[{"id":"challenge","kind":"trial","name":"CHALLENGE (CCTG CO.21)","route":"/trials/challenge/","status":"positive","tldr":"The first randomised trial to show that a coached exercise programme after cancer treatment reduces recurrence and death, in colon cancer."},{"id":"cctg","kind":"company","name":"Canadian Cancer Trials Group (CCTG)","route":"/companies/cctg/","tldr":"Canada's national academic trials group, which ran the CHALLENGE exercise trial and co-led the SABR-COMET oligometastasis trial."},{"id":"exercise-oncology","kind":"technology","name":"Exercise & lifestyle oncology","route":"/technologies/exercise-oncology/","status":"established","tldr":"Structured exercise during and after treatment, which the CHALLENGE trial showed improves survival in colon cancer."},{"id":"structured-exercise-survivorship","kind":"technology","name":"Structured exercise programmes after curative treatment","route":"/technologies/structured-exercise-survivorship/","status":"established","tldr":"A supervised, coached exercise programme for three years after bowel cancer treatment cut recurrence and death in a large randomised trial. It is the first lifestyle intervention proven to work like an adjuvant drug."},{"id":"exercise-during-chemotherapy","kind":"technology","name":"Exercise during chemotherapy and radiotherapy","route":"/technologies/exercise-during-chemotherapy/","status":"established","tldr":"Moderate exercise while on chemotherapy is safe and reduces fatigue, helps people finish their planned doses, and may protect the heart and nerves."},{"id":"prehabilitation","kind":"technology","name":"Prehabilitation before cancer surgery","route":"/technologies/prehabilitation/","status":"emerging","tldr":"Prehabilitation is a few weeks of structured exercise, nutrition and psychological preparation between diagnosis and surgery to make patients fitter for the operation and speed recovery."},{"id":"prehab-trial","kind":"trial","name":"PREHAB: multimodal prehabilitation before colorectal cancer surgery","route":"/trials/prehab-trial/","status":"positive","tldr":"PREHAB showed that four weeks of supervised training, protein and support before bowel cancer surgery cut severe complications and sped recovery, in an international randomised trial of 251 patients."},{"id":"eras-perioperative-nutrition","kind":"technology","name":"Enhanced recovery (ERAS) and perioperative nutrition","route":"/technologies/eras-perioperative-nutrition/","status":"standard-of-care","tldr":"Instead of starving patients before and after an operation, modern surgical pathways feed them early, give carbohydrate drinks the night before, and get them walking the next day. Complications and hospital stays fall."},{"id":"idea-exercise-as-adjuvant","kind":"idea","name":"Structured exercise prescribed like a drug in all curative-intent cancer care","route":"/ideas/idea-exercise-as-adjuvant/","tldr":"The CHALLENGE trial showed a supervised exercise programme improves survival in colon cancer. Extend it to breast, prostate, and lung cancer with the same rigour."},{"id":"idea-bio2-exercise-reimbursement","kind":"idea","name":"Pay for supervised exercise the way we pay for drugs","route":"/ideas/idea-bio2-exercise-reimbursement/","tldr":"A large trial showed a structured exercise programme improved survival after bowel cancer. Almost no health system pays for it, so almost no patient gets it."},{"id":"idea-bio2-prehabilitation-standard","kind":"idea","name":"Four weeks of training and nutrition before major cancer surgery, as standard","route":"/ideas/idea-bio2-prehabilitation-standard/","tldr":"Getting fitter and better nourished before an operation reduces complications and speeds recovery. It is cheap, but only a few hospitals do it."}],"trials":[{"id":"challenge","name":"CHALLENGE (CCTG CO.21)","route":"/trials/challenge/","outcomes":[{"endpoint":"Disease-free survival at 5 years","primary":true,"unit":"%","arms":[{"name":"Structured exercise","n":445,"value":80.3},{"name":"Health education","n":444,"value":73.9}],"hr":0.72,"ci":[0.55,0.94],"p":"0.02","source":"https://doi.org/10.1056/NEJMoa2502760"},{"endpoint":"Overall survival at 8 years","unit":"%","arms":[{"name":"Structured exercise","value":90.3},{"name":"Health education","value":83.2}],"hr":0.63,"ci":[0.43,0.94],"source":"https://doi.org/10.1056/NEJMoa2502760"}],"setting":"Resected stage III or high-risk stage II colon cancer after adjuvant chemotherapy: 3-year structured exercise programme vs health-education materials","enrolled":889,"enrolledBasis":"registry"},{"id":"prehab-trial","name":"PREHAB: multimodal prehabilitation before colorectal cancer surgery","route":"/trials/prehab-trial/","outcomes":[{"endpoint":"Severe postoperative complications (Comprehensive Complication Index > 20)","primary":true,"unit":"%","arms":[{"name":"Multimodal prehabilitation","n":123,"value":17.1,"note":"Odds ratio 0.47 (95% CI 0.26-0.87)"},{"name":"Standard care (ERAS)","n":128,"value":29.7}],"p":"0.02","source":"https://doi.org/10.1001/jamasurg.2023.0198"},{"endpoint":"Medical complications","unit":"%","arms":[{"name":"Multimodal prehabilitation","value":15.4,"note":"Odds ratio 0.48 (95% CI 0.26-0.89)"},{"name":"Standard care (ERAS)","value":27.3}],"p":"0.02","source":"https://doi.org/10.1001/jamasurg.2023.0198"},{"endpoint":"6-minute walking distance at 4 weeks post-operatively (change from baseline)","primary":true,"arms":[{"name":"Multimodal prehabilitation","note":"Mean difference 15.6 m (95% CI -1.4 to 32.6); not significant. Trial stopped early because of COVID-19."},{"name":"Standard care (ERAS)"}],"p":"0.07","source":"https://doi.org/10.1001/jamasurg.2023.0198"}],"setting":"Non-metastatic colorectal cancer scheduled for elective resection within an ERAS pathway: 4-week supervised multimodal prehabilitation (high-intensity exercise, nutrition, psychological support, smoking cessation) vs ERAS alone","enrolled":251,"enrolledBasis":"registry"}],"papers":[]},{"era":"2015-2026","title":"Nutrition care as a standard of care","description":"Weighing every patient, screening for malnutrition, dietitian-led counselling and, when needed, tube or intravenous feeding are in ESPEN and ASCO guidelines because malnutrition predicts toxicity, complications and death. Immunonutrition before major surgery, a Mediterranean pattern for survivors, and dietitian-led weight loss in hormone-positive breast cancer (the 3,000-patient BWEL trial is awaited) are the evidence-based options. Soy is safe; most supplements are unnecessary and some interact with treatment.","status":"current","refs":[{"id":"oncology-nutrition","kind":"technology","name":"Nutrition support and cachexia management","route":"/technologies/oncology-nutrition/","status":"established","tldr":"Screening for malnutrition, dietitian-led counselling, supplements and tube or intravenous feeding where indicated, plus treatment of cancer cachexia, the muscle-wasting syndrome that affects up to 80% of advanced patients."},{"id":"nutrition-screening-mnt","kind":"technology","name":"Oncology nutrition assessment and medical nutrition therapy","route":"/technologies/nutrition-screening-mnt/","status":"established","tldr":"Nutrition screening means weighing every patient, asking a few screening questions, and referring those at risk to a dietitian. It is simple, guideline-endorsed, and still not done routinely."},{"id":"malnutrition-screening","kind":"term","name":"Malnutrition screening tools (MUST, NRS-2002, MST, PG-SGA)","route":"/terms/malnutrition-screening/","tldr":"Quick questionnaires that flag who is at risk of malnutrition: recent weight loss, low BMI, poor appetite, illness severity. Anyone flagged should see a dietitian."},{"id":"enteral-parenteral-nutrition","kind":"technology","name":"Enteral and parenteral nutrition support","route":"/technologies/enteral-parenteral-nutrition/","status":"established","tldr":"Nutrition support means tube feeding into the gut, or nutrition into a vein when the gut cannot be used. It is life-saving in the right patient, harmful or futile in the wrong one."},{"id":"immunonutrition-perioperative","kind":"technology","name":"Immunonutrition before cancer surgery","route":"/technologies/immunonutrition-perioperative/","status":"emerging","tldr":"Drinks enriched with arginine, omega-3 fats and nucleotides for a week before a big operation seem to reduce infections afterwards, though the trials are old and mostly industry-funded."},{"id":"mediterranean-plant-forward-diet","kind":"technology","name":"Mediterranean and plant-forward dietary patterns","route":"/technologies/mediterranean-plant-forward-diet/","status":"established","tldr":"Diets built around vegetables, wholegrains, legumes, nuts, fish and olive oil, with little red or processed meat, are linked with lower cancer risk and better survival after diagnosis. The evidence is strong for the pattern, weak for any single food."},{"id":"dietitian-led-weight-loss-breast","kind":"technology","name":"Dietitian-led weight-loss programmes in HR-positive breast cancer","route":"/technologies/dietitian-led-weight-loss-breast/","status":"phase-3","tldr":"Being overweight after breast cancer is linked with more recurrence, so a 3,000-woman trial tested a two-year telephone weight-loss programme. Women lost weight, but the trial did not clearly show fewer recurrences."},{"id":"bwel","kind":"trial","name":"BWEL (Breast Cancer Weight Loss, Alliance A011401)","route":"/trials/bwel/","status":"mixed","tldr":"BWEL is a trial of more than 3,000 women testing whether losing weight after breast cancer treatment reduces recurrence. The programme achieved weight loss; the effect on recurrence was not clearly shown at the first analysis."},{"id":"espen","kind":"institution","name":"European Society for Clinical Nutrition and Metabolism","route":"/institutions/espen/","tldr":"The European clinical nutrition society whose guidelines on nutrition in cancer patients define screening for malnutrition and the treatment of cachexia in oncology."},{"id":"sarcopenia","kind":"term","name":"Sarcopenia","route":"/terms/sarcopenia/","tldr":"Sarcopenia is loss of muscle mass and strength. In cancer it predicts worse chemotherapy side-effects, more surgical complications and shorter survival, and it can hide in people who look a normal weight or overweight."}],"trials":[{"id":"bwel","name":"BWEL (Breast Cancer Weight Loss, Alliance A011401)","route":"/trials/bwel/","outcomes":[{"endpoint":"Invasive disease-free survival","primary":true,"unit":"months","arms":[{"name":"Telephone weight-loss intervention + health education","note":"Event-driven primary analysis not yet published; ClinicalTrials.gov lists primary completion in 2030. Only weight and quality-of-life secondary analyses have been reported (2025-2026)."},{"name":"Health education alone"}],"source":"https://clinicaltrials.gov/study/NCT02750826"},{"endpoint":"Weight change from baseline at 1 year","unit":"%","arms":[{"name":"Telephone weight-loss intervention + health education","n":1591,"value":-4.7,"note":"Mean -4.3 kg vs +0.9 kg; 3,180 women analysed"},{"name":"Health education alone","n":1589,"value":1}],"p":"<0.001","source":"https://doi.org/10.1001/jamaoncol.2025.2738"}],"setting":"Stage II-III HR-positive or HER2-positive breast cancer, BMI at least 27: 2-year telephone-based weight-loss intervention plus health education vs health education alone","enrolled":3181,"enrolledBasis":"registry"}],"papers":[]},{"era":"2024-2028","title":"The microbiome and immunotherapy","description":"Patients who eat plenty of fibre and avoid unnecessary antibiotics respond better to checkpoint inhibitors in observational studies, and small trials of faecal microbiota transplantation from responders or healthy donors converted some non-responders into responders (Pittsburgh, MIMic-01). Defined bacterial consortia and stewardship of antibiotics around immunotherapy are the next tests. This is the one area of nutrition where a mechanism, the gut's training of the immune system, is being tested in randomised trials with response as the endpoint.","status":"emerging","refs":[{"id":"dietary-fibre-microbiome-io","kind":"technology","name":"Dietary fibre and the gut microbiome for immunotherapy response","route":"/technologies/dietary-fibre-microbiome-io/","status":"emerging","tldr":"Patients who eat plenty of fibre and avoid probiotic pills seem to respond better to immunotherapy for melanoma, probably because fibre feeds the right gut bacteria. A proper trial is under way."},{"id":"fmt-checkpoint-nonresponders","kind":"technology","name":"Faecal microbiota transplantation for PD-1 non-responders","route":"/technologies/fmt-checkpoint-nonresponders/","status":"phase-2","tldr":"Transplanting gut bacteria from patients who responded to immunotherapy into those who did not. In small studies a minority of resistant melanomas started responding. Randomised trials are running."},{"id":"fmt-pd1-refractory-melanoma-pitt","kind":"trial","name":"FMT plus pembrolizumab in anti-PD-1-refractory melanoma (Pittsburgh)","route":"/trials/fmt-pd1-refractory-melanoma-pitt/","status":"completed","tldr":"Fifteen melanoma patients whose immunotherapy had failed received a stool transplant from someone whose immunotherapy had worked, then restarted the drug. Six of them benefited, including three with lasting responses."},{"id":"mimic-01","kind":"trial","name":"MIMic-01: healthy-donor FMT plus anti-PD-1, first-line melanoma","route":"/trials/mimic-01/","status":"active","tldr":"Twenty melanoma patients took stool capsules from healthy donors before starting immunotherapy. Thirteen responded, more than usually expected, and the transplant was safe."},{"id":"probiotics-antibiotic-stewardship-io","kind":"technology","name":"Probiotics, antibiotics and stewardship around immunotherapy","route":"/technologies/probiotics-antibiotic-stewardship-io/","status":"emerging","tldr":"Antibiotics in the weeks before immunotherapy are linked with worse outcomes, and shop-bought probiotics may not help and might hurt. Avoiding both where possible is a low-cost precaution."},{"id":"microbiome-modulation-io","kind":"technology","name":"Microbiome modulation to unlock immunotherapy","route":"/technologies/microbiome-modulation-io/","status":"phase-2","tldr":"Changing the gut bacteria of a patient whose immunotherapy stopped working, in the hope of restarting the response."},{"id":"gut-microbiome-diversity","kind":"term","name":"Gut microbiome diversity and composition","route":"/terms/gut-microbiome-diversity/","tldr":"How many different kinds of bacteria live in the gut and which ones dominate. Higher diversity and certain species are linked with better immunotherapy response; antibiotics and poor diet reduce both."},{"id":"maat-pharma","kind":"company","name":"MaaT Pharma","route":"/companies/maat-pharma/","tldr":"MaaT Pharma makes gut microbiome treatments for people with blood cancer. Its lead product restores gut bacteria to treat a severe complication of stem cell transplants when standard drugs fail."}],"trials":[{"id":"fmt-pd1-refractory-melanoma-pitt","name":"FMT plus pembrolizumab in anti-PD-1-refractory melanoma (Pittsburgh)","route":"/trials/fmt-pd1-refractory-melanoma-pitt/","outcomes":[{"endpoint":"Clinical benefit (objective response or SD over 12 months)","primary":true,"unit":"%","arms":[{"name":"FMT + pembrolizumab","n":15,"value":40}],"source":"https://doi.org/10.1126/science.abf3363"}],"setting":"Metastatic melanoma with primary resistance to anti-PD-1: single colonoscopic FMT from a durable responder donor, then pembrolizumab","enrolled":15,"enrolledNote":"ClinicalTrials.gov lists 20 participants (actual); the Science 2021 paper reports outcomes for the 15 patients who received FMT plus pembrolizumab.","enrolledBasis":"treated"},{"id":"mimic-01","name":"MIMic-01: healthy-donor FMT plus anti-PD-1, first-line melanoma","route":"/trials/mimic-01/","outcomes":[{"endpoint":"Objective response rate","unit":"%","arms":[{"name":"FMT + anti-PD-1","n":20,"value":65}],"source":"https://doi.org/10.1038/s41591-023-02453-x"}],"setting":"Untreated advanced melanoma: oral capsule FMT from healthy donors one week before, then with, nivolumab or pembrolizumab","enrolled":20,"enrolledBasis":"registry"}],"papers":[]},{"era":"2025-2030","title":"Metabolic interventions under randomised test","description":"People taking GLP-1 agonists for obesity have lower rates of obesity-related cancers in observational data, and bariatric surgery patients develop fewer cancers, but neither has a randomised trial with cancer as the primary outcome; that trial is the most important one this front could run. Fasting-mimicking diets around chemotherapy, ketogenic diets in glioblastoma (ERGO2 is the only randomised test) and time-restricted eating have plausible mechanisms and small trials. GLP-1 drugs to reverse endometrial precancer in women with obesity is the nearest practical application.","status":"emerging","refs":[{"id":"glp1-agonists-cancer-risk","kind":"technology","name":"GLP-1 receptor agonists and obesity-related cancer risk","route":"/technologies/glp1-agonists-cancer-risk/","status":"emerging","tldr":"GLP-1 agonists, the new weight-loss injections, lower weight by 15-20%. Early observational data suggest fewer obesity-related cancers in people who take them, but no trial has yet tested cancer as an outcome."},{"id":"bariatric-surgery-cancer-incidence","kind":"technology","name":"Bariatric surgery and cancer incidence","route":"/technologies/bariatric-surgery-cancer-incidence/","status":"established","tldr":"People with severe obesity who have weight-loss surgery develop about a third fewer cancers over the following decade, especially womb and other hormone-related cancers, than similar people who do not."},{"id":"idea-prev-glp1-cancer-prevention-rct","kind":"idea","name":"A trial of GLP-1 weight-loss drugs with cancer as the primary outcome","route":"/ideas/idea-prev-glp1-cancer-prevention-rct/","tldr":"Obesity raises the risk of 13 cancers, and GLP-1 weight-loss drugs are already in routine use for diabetes and obesity. Observational data hint that they cut obesity-related cancers but confounding is severe, so a randomised trial in adults aged 50 to 70 with a BMI of 30 or more should make cancer the primary outcome."},{"id":"idea-prev-glp1-endometrial-hyperplasia","kind":"idea","name":"GLP-1 drugs to reverse endometrial precancer in women with obesity","route":"/ideas/idea-prev-glp1-endometrial-hyperplasia/","tldr":"Womb precancer in women with obesity is usually treated with a hormone coil or hysterectomy. Weight-loss drugs might reverse it and protect fertility."},{"id":"fasting-mimicking-diet","kind":"technology","name":"Fasting and fasting-mimicking diets around chemotherapy","route":"/technologies/fasting-mimicking-diet/","status":"phase-2","tldr":"Fasting-mimicking diets cut food intake for three days around each chemotherapy dose to lower glucose, insulin and IGF-1, which may shield normal cells and sensitise the tumour. The DIRECT trial in early breast cancer improved radiological response but fewer than 20% of patients kept to the diet, and it is unsafe in cachexia or without a dietitian."},{"id":"ketogenic-diet-glioblastoma","kind":"technology","name":"Ketogenic diets in glioblastoma","route":"/technologies/ketogenic-diet-glioblastoma/","status":"phase-2","tldr":"A ketogenic diet restricts carbohydrate so the body runs on ketones, on the theory that glioblastoma cells depend on glucose while neurons can burn ketones. Small trials show it is safe and achievable for three to six months with supervision, but none has shown a benefit against the tumour, and adherence beyond three months is poor."},{"id":"ergo2","kind":"trial","name":"ERGO2: ketogenic diet and fasting during re-irradiation of recurrent glioma","route":"/trials/ergo2/","status":"negative","tldr":"The only randomised trial of a ketogenic diet in brain tumours found no benefit. Patients could follow the diet and their ketone levels rose, but progression came just as quickly."},{"id":"time-restricted-eating","kind":"technology","name":"Time-restricted eating in cancer prevention and survivorship","route":"/technologies/time-restricted-eating/","status":"phase-2","tldr":"Time-restricted eating means eating within a window of 8-12 hours a day and fasting overnight. It improves blood sugar and weight a little; whether it changes cancer risk or recurrence is unknown."}],"trials":[{"id":"ergo2","name":"ERGO2: ketogenic diet and fasting during re-irradiation of recurrent glioma","route":"/trials/ergo2/","outcomes":[{"endpoint":"Progression-free survival at 6 months","primary":true,"unit":"%","arms":[{"name":"Ketogenic diet + fasting","n":25,"value":20},{"name":"Standard diet","n":25,"value":16}],"source":"https://doi.org/10.1016/j.ijrobp.2020.06.021"}],"setting":"Recurrent glioblastoma and other malignant gliomas undergoing re-irradiation: 6-day calorie-restricted ketogenic diet plus 3-day fasting during radiotherapy vs standard diet","enrolled":50,"enrolledBasis":"registry"}],"papers":[]},{"era":"2026-2030","title":"Cachexia as a treatable disease","description":"Cancer wasting is driven in part by the hormone GDF-15, and the first antibody against it (ponsegromab) improved weight and physical activity in phase 2. Low-dose olanzapine restored appetite in a Tata Memorial trial for pennies; resistance training and protein remain the foundation. The proposal is to treat cachexia like sepsis, with a trigger, a bundle and an audit, and to combine the new antibody with exercise and nutrition rather than test it alone.","status":"emerging","refs":[{"id":"cachexia","kind":"term","name":"Cancer cachexia","route":"/terms/cachexia/","tldr":"Severe loss of weight and muscle in advanced cancer that eating more cannot reverse on its own. It affects up to eight in ten patients with advanced disease and contributes to a fifth of cancer deaths."},{"id":"cachexia-therapy","kind":"technology","name":"Cachexia-directed therapy (GDF-15 blockade)","route":"/technologies/cachexia-therapy/","status":"phase-3","tldr":"Cachexia-directed therapy treats cancer wasting by blocking GDF-15, a hormone that rises in advanced cancer and acts on the brainstem to suppress appetite. Pfizer's antibody ponsegromab improved weight in a phase 2 trial and is in phase 2/3 in pancreatic cancer cachexia; whether weight gain translates into function is the open question."},{"id":"ponsegromab-phase-2","kind":"trial","name":"Ponsegromab phase 2 in cancer cachexia","route":"/trials/ponsegromab-phase-2/","status":"positive","tldr":"The first drug to hit the hormone behind cancer wasting: patients on the highest dose gained nearly 3 kg more than placebo in 12 weeks and reported better appetite and more activity."},{"id":"cachexia-appetite-pharmacotherapy","kind":"technology","name":"Cachexia pharmacotherapy: GDF-15 blockade, anamorelin, olanzapine","route":"/technologies/cachexia-appetite-pharmacotherapy/","status":"phase-3","tldr":"Cachexia pharmacotherapy covers three drug approaches to cancer wasting: ponsegromab, an antibody that blocks the appetite-suppressing hormone GDF-15 and is in phase 3; anamorelin, a ghrelin mimic approved only in Japan; and low-dose olanzapine, a generic tablet available everywhere that ASCO added to guidance in 2024. None has yet been shown to improve physical function."},{"id":"olanzapine-appetite-tmh","kind":"trial","name":"Low-dose olanzapine for cancer anorexia (Tata Memorial)","route":"/trials/olanzapine-appetite-tmh/","status":"positive","tldr":"A double-blind trial at Tata Memorial in India randomised 124 patients starting chemotherapy to 2.5 mg of olanzapine, a decades-old tablet costing a few cents a day, or placebo. Six in ten gained more than 5% of their weight against one in ten on placebo, and ASCO listed it in its 2024 cachexia guideline; it was small and single-centre."},{"id":"resistance-training-cachexia","kind":"technology","name":"Resistance training and protein for cachexia and sarcopenia","route":"/technologies/resistance-training-cachexia/","status":"emerging","tldr":"Lifting weights and eating enough protein is the only treatment shown to build muscle in people with cancer wasting, but most are too unwell to do it alone and the trials are small."},{"id":"idea-bio2-gdf15-plus-exercise","kind":"idea","name":"Combine the new anti-wasting antibody with exercise and protein","route":"/ideas/idea-bio2-gdf15-plus-exercise/","tldr":"A new antibody blocks the hormone that makes people with cancer lose appetite and weight. Weight regained as muscle, not fat, needs exercise and protein alongside it."},{"id":"idea-cachexia-gdf15-prevention","kind":"idea","name":"Treat cachexia before it starts","route":"/ideas/idea-cachexia-gdf15-prevention/","tldr":"Cachexia, the muscle wasting driven partly by the hormone GDF-15, kills cancer patients and stops chemotherapy being completed, and late muscle loss is largely irreversible. Ponsegromab, an anti-GDF-15 antibody, reversed weight loss in established cachexia in 2024; the next test is a phase 3 giving it from first-line chemotherapy in pancreatic cancer to prevent wasting rather than treat it."}],"trials":[{"id":"ponsegromab-phase-2","name":"Ponsegromab phase 2 in cancer cachexia","route":"/trials/ponsegromab-phase-2/","outcomes":[{"endpoint":"Change in body weight at 12 weeks (placebo-adjusted)","primary":true,"unit":"kg","arms":[{"name":"Ponsegromab 400 mg","value":2.81},{"name":"Ponsegromab 200 mg","value":1.92},{"name":"Ponsegromab 100 mg","value":1.22},{"name":"Placebo","value":0}],"source":"https://doi.org/10.1056/NEJMoa2409515"}],"setting":"NSCLC, pancreatic or colorectal cancer with cachexia and elevated serum GDF-15: ponsegromab 100, 200 or 400 mg subcutaneously every 4 weeks vs placebo for 12 weeks","enrolled":187,"enrolledBasis":"registry"},{"id":"olanzapine-appetite-tmh","name":"Low-dose olanzapine for cancer anorexia (Tata Memorial)","route":"/trials/olanzapine-appetite-tmh/","outcomes":[{"endpoint":"Weight gain greater than 5% at 12 weeks","primary":true,"unit":"%","arms":[{"name":"Olanzapine 2.5 mg","n":63,"value":60},{"name":"Placebo","n":61,"value":9}],"p":"<0.001","source":"https://doi.org/10.1200/JCO.22.01997"}],"setting":"Untreated, locally advanced or metastatic gastric, hepatopancreaticobiliary or lung cancer starting chemotherapy: olanzapine 2.5 mg daily vs placebo for 12 weeks, plus standard nutritional advice","enrolled":124,"enrolledBasis":"registry"}],"papers":[]},{"era":"2030+","title":"Exercise dosed like a drug, and sleep as a target","description":"CHALLENGE proved exercise works in one cancer at one dose; dose-finding trials across cancers, reimbursement of supervised programmes as treatment, and delivery at population scale are the next decade's work. Half of people with cancer sleep badly, and trials are asking whether treating insomnia and restoring circadian rhythm changes outcomes. Evidence-based integrative oncology in every centre is the proposed bridge that meets patient demand without ceding ground to unproven regimens.","status":"speculative","refs":[{"id":"idea-nl-exercise-dose-finding","kind":"idea","name":"A dose-finding trial for exercise after cancer","route":"/ideas/idea-nl-exercise-dose-finding/","tldr":"CHALLENGE proved exercise works in colon cancer but not how much is needed. A trial comparing doses, as we would for a drug, would tell health systems what to fund."},{"id":"idea-exercise-as-adjuvant","kind":"idea","name":"Structured exercise prescribed like a drug in all curative-intent cancer care","route":"/ideas/idea-exercise-as-adjuvant/","tldr":"The CHALLENGE trial showed a supervised exercise programme improves survival in colon cancer. Extend it to breast, prostate, and lung cancer with the same rigour."},{"id":"sleep-circadian-interventions","kind":"technology","name":"Sleep and circadian interventions in cancer","route":"/technologies/sleep-circadian-interventions/","status":"emerging","tldr":"Half of people with cancer sleep badly, so sleep and body-clock interventions matter. Talking therapy for insomnia works well and is under-used; whether fixing sleep or body-clock disruption changes the cancer itself is unproven."},{"id":"idea-nl-sleep-circadian-survivorship-rct","kind":"idea","name":"Treat insomnia in survivors and measure whether the cancer notices","route":"/ideas/idea-nl-sleep-circadian-survivorship-rct/","tldr":"Insomnia therapy works well for cancer survivors and is barely offered. A trial that fixes sleep and then follows recurrence would test whether restoring the body clock changes the disease as well as the symptom."},{"id":"integrative-oncology","kind":"technology","name":"Evidence-based integrative oncology","route":"/technologies/integrative-oncology/","status":"established","tldr":"Using complementary approaches with real evidence, such as acupuncture for nausea and pain, yoga and mindfulness for anxiety and fatigue, alongside standard treatment, while steering patients away from unproven 'alternative' therapies that can shorten life."},{"id":"yoga-cancer","kind":"technology","name":"Yoga during and after cancer treatment","route":"/technologies/yoga-cancer/","status":"established","tldr":"Yoga combining postures, breathing and relaxation reduces fatigue, anxiety and low mood and improves sleep and quality of life, on the evidence of a Cochrane review of 24 randomised trials in women with breast cancer. SIO-ASCO guidelines recommend it for fatigue and anxiety during treatment; it does not replace aerobic and resistance exercise."},{"id":"idea-moon-integrative-oncology-bridge","kind":"idea","name":"Evidence-based integrative oncology in every cancer centre to meet demand safely","route":"/ideas/idea-moon-integrative-oncology-bridge/","tldr":"Offer the complementary approaches that have evidence (acupuncture for nausea and pain, exercise, mindfulness, yoga) inside the cancer centre, so patients do not seek them, and worse, elsewhere."}],"trials":[],"papers":[]},{"era":"What sets the pace","title":"No patent, no sponsor, plenty of noise","description":"Nothing on this front can be patented, so trials depend on public and charitable funders and are rare; misinformation fills the space with alkaline diets and juice cures; health systems pay for drugs but not for dietitians or exercise physiologists; and the prevention measures already proven (alcohol pricing and labelling, sugar taxes, active travel) are politically harder than any drug approval. Cancer warning labels on alcohol, evaluated as a natural experiment, would be a start.","status":"current","refs":[{"id":"b-cachexia-supportive","kind":"bottleneck","name":"Cachexia, toxicity and the limits of the patient","route":"/bottlenecks/b-cachexia-supportive/","tldr":"Cancer cachexia, the muscle and fat wasting driven by tumour and host inflammatory signals, affects most patients with advanced pancreatic, gastric and lung cancer, and treatment-limiting toxicities decide what dose a patient can receive. Only Japan has an approved cachexia drug, and supportive care research gets a small share of funding relative to its effect."},{"id":"b-prevention-adoption","kind":"bottleneck","name":"Prevention we already have is not deployed","route":"/bottlenecks/b-prevention-adoption/","tldr":"Around four in ten cancers are preventable with tools we already own: vaccines, tobacco control, weight, alcohol, sun and infection control."},{"id":"b-misinformation","kind":"bottleneck","name":"Misinformation and unproven therapies","route":"/bottlenecks/b-misinformation/","tldr":"Patients are sold unproven treatments and frightened away from proven ones."},{"id":"b-generic-repurposing","kind":"bottleneck","name":"No incentive to repurpose cheap drugs","route":"/bottlenecks/b-generic-repurposing/","tldr":"Old, cheap drugs with anti-cancer signals never get the trials they need because no one profits from the result."},{"id":"b-funding-allocation","kind":"bottleneck","name":"Funding follows fashion, not burden","route":"/bottlenecks/b-funding-allocation/","tldr":"Research money follows visibility, not burden: breast, prostate and leukaemia receive far more funding per death or year of life lost than lung, pancreatic, liver, oesophageal, gastric, bladder and uterine cancers, and metastasis research gets an estimated 5% of funding despite causing most deaths. Advocacy strength and peer review that rewards mechanism explain the skew."},{"id":"idea-prev-alcohol-cancer-warning-labels","kind":"idea","name":"Cancer warnings on alcohol labels, evaluated as a natural experiment","route":"/ideas/idea-prev-alcohol-cancer-warning-labels/","tldr":"Most people do not know alcohol causes seven cancers. Ireland is putting cancer warnings on bottles; other countries should follow and measure the effect on drinking."},{"id":"idea-prev-minimum-unit-pricing-cancer-endpoints","kind":"idea","name":"Minimum alcohol pricing evaluated with cancer endpoints","route":"/ideas/idea-prev-minimum-unit-pricing-cancer-endpoints/","tldr":"Scotland's minimum price per unit cut alcohol deaths. Tracking alcohol-related cancer incidence over the next decade would show whether it also prevents cancer."},{"id":"smoking-cessation-after-diagnosis","kind":"technology","name":"Smoking cessation in cancer patients","route":"/technologies/smoking-cessation-after-diagnosis/","status":"established","tldr":"Stopping smoking after a cancer diagnosis improves survival, reduces treatment complications and second cancers, and is the single most effective supportive intervention that oncology services still routinely fail to deliver."}],"trials":[],"papers":[]}],"watch":[]}