01Core principlesThe concepts and mechanisms needed to understand the subject.
Treatment labels describe timing, not a universal recipe. Neoadjuvant therapy precedes a planned operation; adjuvant therapy follows it; perioperative protocols deliberately span both. Oesophageal squamous cancer is radiosensitive and may be treated definitively without surgery. Adenocarcinoma at the oesophagus, junction or stomach has several valid multimodality strategies whose choice depends on exact anatomical classification and current specialist guidance.
FLOT is a high-intensity regimen for selected fit adults with resectable gastric or junctional adenocarcinoma. Each 14-day cycle uses docetaxel, oxaliplatin, folinate and a 24-hour fluorouracil infusion, with steroid and antiemetic support under a cancer protocol. Baseline blood count, renal and liver function, performance status and DPD testing inform safety. Toxicities include neutropenia, infection, mucositis, diarrhoea, neuropathy, hypersensitivity and fluoropyrimidine cardiac toxicity.
Palliative systemic therapy is selected from tumour biology and previous exposure, not merely the organ label. A patient with immediate severe dysphagia may need a stent before treatment can work; another with a longer prognosis may prefer radiotherapy. Regular response review asks whether cancer control and quality of life still justify toxicity, while dietetic and palliative teams manage symptoms alongside oncology.
Key points
- Neoadjuvant treatment is given before surgery to treat micrometastatic disease, test biology and improve resection; perioperative therapy includes planned pre- and postoperative components.
- The Thames Valley January 2025 v5.1 FLOT example is for fit PS 0–1 adults with resectable gastric or junctional adenocarcinoma: four 14-day cycles before surgery and, only after recovery and review, four after surgery.
- Day 1 gives docetaxel 50 mg/m² IV over 60 minutes in sodium chloride 0.9%, calcium folinate 350 mg with oxaliplatin 85 mg/m² in glucose 5% over 2 hours, then fluorouracil 2600 mg/m² by continuous IV infusion over 24 hours; GCSF starts at least 24 hours later.
- For localised oesophageal or junctional adenocarcinoma beyond T1N0 proceeding to surgery, NICE offers chemotherapy before surgery, chemotherapy before and after surgery, or chemoradiotherapy before surgery. Definitive chemoradiotherapy remains an important curative option for squamous cancer and selected non-operative patients.
- NICE treatment branches are site- and biomarker-specific: nivolumab plus platinum/fluoropyrimidine for untreated HER2-negative advanced oesophageal adenocarcinoma with PD-L1 CPS at least 5; trastuzumab plus cisplatin with capecitabine or fluorouracil for untreated HER2-positive metastatic gastric or junctional adenocarcinoma; and adjuvant nivolumab for completely resected oesophageal or junctional cancer with residual disease after neoadjuvant chemoradiotherapy.
- Palliative treatment includes systemic control, radiotherapy, stenting, nutrition, analgesia and advance care planning; its purpose and stopping rules should be explicit.
02Mechanisms and patternsImportant relationships and how to distinguish them.
Performance status, organ function and nutrition support perioperative therapy before radical gastric or junctional surgery.
Definitive chemoradiotherapy may offer curative treatment without oesophagectomy in appropriate squamous disease.
HER2, MMR or MSI and PD-L1 results can determine which targeted or immune options are available.
Fever, rigors, hypotension or sudden deterioration during chemotherapy requires emergency sepsis assessment.
New chest pain during or shortly after fluorouracil infusion requires immediate interruption and cardiac evaluation.
03Interpreting evidenceInformation, measurements and their limitations.
Consider the information, its meaning and its limitations before deciding what follows.
- 01
FLOT pretreatment blood count and organ review - Why
- Confirm eligibility for each cycle of this specialist protocol.
- Interpretation and limitations
- Check FBC, U&E, LFTs, creatinine, weight and toxicity every cycle. Require neutrophils at least 1.5 × 10⁹/L and platelets at least 100 × 10⁹/L; below either threshold delay treatment. If both recover within 2 weeks the local protocol resumes 100% dose; otherwise the consultant decides the specified reductions. With CrCl below 30 mL/min, pause cycle authorisation for consultant-led oxaliplatin reduction; v5.1 says consider 50% of the original dose. Deteriorating liver function requires consultant review before proceeding: bilirubin above 50 micromol/L may require stopping or changing treatment, and fluorouracil is not recommended above 85 micromol/L.
- 02
Pretreatment DPD assessment - Why
- Identify major risk of severe fluoropyrimidine toxicity before fluorouracil.
- Interpretation and limitations
- Do not give systemic fluoropyrimidine to known complete DPD deficiency; in partial deficiency consider a reduced starting dose. A negative test does not eliminate severe toxicity, so monitor closely in cycle 1 and after dose increases.
- 03
Site-specific tumour biomarkers - Why
- Select an evidence-based targeted or immune regimen in advanced disease.
- Interpretation and limitations
- Offer HER2 testing in advanced oesophago-gastric adenocarcinoma and interpret PD-L1 and MMR/MSI separately. Examples include trastuzumab with cisplatin plus capecitabine or fluorouracil for untreated HER2-positive metastatic gastric/junctional adenocarcinoma, and pembrolizumab after one prior therapy for unresectable or metastatic MSI-high/MMR-deficient gastric cancer.
- 04
Interval restaging - Why
- Determine response and continued resectability after neoadjuvant therapy.
- Interpretation and limitations
- Inflammation can complicate local interpretation; the MDT integrates baseline stage, new metastases and fitness.
- 05
Toxicity assessment before each cycle - Why
- Decide whether to proceed, delay, reduce or stop.
- Interpretation and limitations
- Grade infection, mucositis, bowel symptoms, neuropathy and functional decline and verify recovery before another dose.
04Applied reasoningWorked examples connecting principles to decisions.
01Worked case: perioperative FLOTDeliver the preoperative component and reassessA fit 55-year-old with resectable gastric adenocarcinoma has normal DPD testing, adequate marrow, renal and hepatic function, and an MDT plan for perioperative FLOT followed by gastrectomy.+
- 1Confirm PS 0–1, baseline DPYD result, FBC, U&E, LFTs, creatinine, weight, nutrition and central access. Give dexamethasone 8 mg by mouth twice daily from 24 hours before treatment, or 20 mg IV on chemotherapy day if that was not taken, then 8 mg twice daily for 2 days after chemotherapy.
- 2Each 14-day cycle gives docetaxel 50 mg/m² in sodium chloride 0.9% over 60 minutes, calcium folinate 350 mg and oxaliplatin 85 mg/m² concurrently in glucose 5% over 2 hours, then fluorouracil 2600 mg/m² continuously over 24 hours; start GCSF at least 24 hours after chemotherapy. Four preoperative cycles are delivered with counts above protocol thresholds.
- 3Restaging CT shows no new metastasis and the patient retains operative fitness, so the MDT confirms gastrectomy rather than continuing chemotherapy without the planned source operation.
- 4After R0 resection, review healing, pathology, performance status, neuropathy and marrow, renal and hepatic recovery; the patient is fit to begin the planned four postoperative cycles, with a fresh proceed/hold decision before each cycle.
02Worked case: chest pain on infusionStop and assess cardiotoxicityHalfway through a fluorouracil pump, a patient develops constricting central chest pain.+
- 1Stop the fluorouracil infusion and contact acute oncology immediately.
- 2Assess ABCDE, ECG and cardiac biomarkers while treating an acute coronary syndrome as clinically indicated.
- 3Do not restart fluoropyrimidine automatically after symptoms settle; obtain oncology and cardiology risk review.
- 4Document the causality decision and alternative cancer plan before further systemic therapy.
03Worked case: palliative obstructionTreat the symptom and cancerMetastatic oesophageal cancer causes rapidly worsening dysphagia while biomarkers are pending.+
- 1Assess airway, aspiration, hydration, nutrition, performance status and the speed of required relief.
- 2Use a self-expanding stent for immediate luminal relief when appropriate, coordinating with systemic treatment.
- 3Test HER2, PD-L1 and MMR/MSI as indicated. If this is untreated HER2-negative advanced oesophageal adenocarcinoma with PD-L1 CPS 6, discuss nivolumab with platinum- and fluoropyrimidine-based chemotherapy; do not extrapolate that regimen to another site, histology or threshold.
- 4Review swallowing, stent complications, weight and quality of life after the intervention.
05Relevant medicines and safetySpecific regimens and precautions where medicines are relevant.
Thames Valley Cancer Alliance perioperative FLOT v5.1 (January 2025 specialist example)
For a fit PS 0–1 adult, give four cycles before surgery and, subject to postoperative recovery and review, four cycles afterwards. Every 14 days on day 1: docetaxel 50 mg/m² IV in sodium chloride 0.9% over 60 minutes; calcium folinate 350 mg IV and oxaliplatin 85 mg/m² IV concurrently in glucose 5% over 2 hours; then fluorouracil 2600 mg/m² by continuous IV infusion over 24 hours. Dexamethasone is 8 mg by mouth twice daily from 24 hours before chemotherapy, or 20 mg IV on the treatment day, followed by 8 mg twice daily for 2 days; start GCSF at least 24 hours after chemotherapy.Confirm DPYD status, PS 0–1, FBC, U&E, LFTs, creatinine and weight. Require neutrophils at least 1.5 × 10⁹/L and platelets at least 100 × 10⁹/L; otherwise delay. If both recover within 2 weeks, the local protocol resumes 100% dose. If they do not, the consultant reviews treatment; the protocol specifies no more than 75% oxaliplatin and docetaxel, while fluorouracil is maintained unless platelets are below 10 × 10⁹/L and neutrophils below 0.5 × 10⁹/L. Use glucose-compatible administration for oxaliplatin and folinate. Stop and assess fever, severe diarrhoea or mucositis, progressive neuropathy, hypersensitivity, pump failure or chest pain; a negative DPD test does not remove serious fluoropyrimidine risk. Before authorising the next cycle, refer CrCl below 30 mL/min for consultant-led oxaliplatin dose reduction; this local protocol says consider 50% of the original dose. Refer any deteriorating hepatic function for consultant review; bilirubin above 50 micromol/L may indicate progression and require cessation or a regimen change, while fluorouracil is not recommended when bilirubin exceeds 85 micromol/L. Do not proceed with unchanged FLOT while these decisions are pending. The docetaxel hepatic table refers to a 100 mg/m² starting dose: its 75 mg/m² entry must not be substituted for this regimen's 50 mg/m² dose.
06Checking understandingVerify the reasoning, revisit uncertainties and apply feedback.
- Check blood count, renal and liver profile and toxicity before every cycle.
- Record weight, intake and performance status because declining reserve changes treatment benefit and dose safety.
- Use interval imaging and MDT review to confirm continued resectability after neoadjuvant treatment.
- After surgery, reassess recovery rather than assuming every patient can complete the postoperative component.
- In palliative care, measure symptom benefit and quality of life against cumulative toxicity at defined review points.
07Special situationsVariants, exceptions and circumstances that change the usual approach.
Perioperative means two decisions
Eligibility before surgery does not guarantee fitness for the postoperative cycles after complications or weight loss.
Regimen names are insufficient prescriptions
FLOT requires exact doses, routes, infusion times, cycle interval and supportive-care checks.
Biology can outrank anatomy in palliation
A biomarker result may change systemic treatment even when the primary site is unchanged.
Local palliation and systemic treatment cooperate
Opening an obstructed lumen can restore nutrition while anticancer therapy addresses broader disease.
08Common pitfallsFrequent interpretation and management errors.
- 01
Calling all preoperative therapy neoadjuvant without documenting the planned postoperative component.
- 02
Starting fluorouracil without DPD assessment and emergency toxicity education.
- 03
Continuing an infusion through chest pain while waiting for clinic review.
- 04
Offering systemic therapy without a planned time to assess benefit and stopping.