{"entity":{"id":"cross","kind":"trial","name":"CROSS","aka":[],"tldr":"The trial that made chemotherapy plus radiation before surgery the standard for oesophageal cancer; the survival gain was still there ten years later.","summary":"CROSS randomised 368 patients with resectable oesophageal or gastro-oesophageal junction cancer to surgery alone or five weekly cycles of carboplatin-paclitaxel with 41.4 Gy in 23 fractions followed by surgery. Median overall survival was 49.4 months with chemoradiation versus 24.0 months with surgery alone, 29 percent had a pathological complete response, and surgical complications were not increased (van Hagen and colleagues, New England Journal of Medicine 2012). Ten-year follow-up confirmed the benefit; the CROSS regimen is a worldwide standard.\n\nOS 49.4 vs 24.0 months (NEJM 2012); pCR 29% (49% in squamous). Ten-year OS 38% vs 25% (JCO 2021), HR for death from oesophageal cancer 0.60. The CROSS regimen is the reference arm for CheckMate 577, SANO, and most modern trials; perioperative FLOT is the alternative for adenocarcinoma (ESOPEC 2024 favoured FLOT).","status":"positive","asOf":"2026-09-07","links":[{"label":"NEJM 2012","url":"https://www.nejm.org/doi/full/10.1056/NEJMoa1112088"},{"label":"10-year outcomes, JCO 2021","url":"https://ascopubs.org/doi/10.1200/JCO.20.03614"}],"tags":[],"related":[],"cancers":["esophageal","oesophageal-squamous-cell-carcinoma","oesophageal-adenocarcinoma","gastric"],"sections":[],"technologies":["imrt-igrt","platinum","cytotoxic-chemotherapy","radiosensitisers"],"targets":[],"drugs":["carboplatin","paclitaxel"],"companies":[],"institutions":[],"pathways":[],"terms":["neoadjuvant-adjuvant","pcr","chemoradiation"],"trials":[],"people":["jan-van-lanschot","kitagawa-yuko"],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"nct":"NTR487","phase":"3","setting":"Resectable oesophageal or junctional cancer (squamous and adenocarcinoma): weekly carboplatin/paclitaxel + 41.4 Gy radiation then surgery vs surgery alone","sponsor":"Dutch Cancer Society (Erasmus MC)","result":"10-year OS 38% vs 25%; median OS 49.4 vs 24.0 months.","yearReported":2012,"enrolled":366,"enrolledBasis":"registry","outcomes":[{"endpoint":"Overall survival","primary":true,"unit":"months","arms":[{"name":"Chemoradiation + surgery","n":178,"value":49.4},{"name":"Surgery alone","n":188,"value":24}],"hr":0.68,"source":"https://www.nejm.org/doi/full/10.1056/NEJMoa1112088"},{"endpoint":"Overall survival at 10 years","unit":"percent","arms":[{"name":"Chemoradiation + surgery","value":38},{"name":"Surgery alone","value":25}],"source":"https://ascopubs.org/doi/10.1200/JCO.20.03614"}],"replication":"Durable at 10 years; NEO-AEGIS and ESOPEC compared it against perioperative chemotherapy in adenocarcinoma with FLOT favoured in ESOPEC."},"route":"/trials/cross/","neighbours":{"cancer":[{"id":"gastric","kind":"cancer","name":"Gastric & gastro-oesophageal junction cancer","route":"/cancers/gastric/"},{"id":"oesophageal-adenocarcinoma","kind":"cancer","name":"Oesophageal and junctional adenocarcinoma","route":"/cancers/oesophageal-adenocarcinoma/"},{"id":"esophageal","kind":"cancer","name":"Oesophageal cancer","route":"/cancers/esophageal/"},{"id":"oesophageal-squamous-cell-carcinoma","kind":"cancer","name":"Oesophageal squamous cell carcinoma","route":"/cancers/oesophageal-squamous-cell-carcinoma/"}],"technology":[{"id":"cytotoxic-chemotherapy","kind":"technology","name":"Cytotoxic chemotherapy","route":"/technologies/cytotoxic-chemotherapy/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"},{"id":"platinum","kind":"technology","name":"Platinum agents","route":"/technologies/platinum/"},{"id":"radiosensitisers","kind":"technology","name":"Radiosensitisers","route":"/technologies/radiosensitisers/"}],"drug":[{"id":"carboplatin","kind":"drug","name":"Carboplatin","route":"/drugs/carboplatin/"},{"id":"paclitaxel","kind":"drug","name":"Paclitaxel / nab-paclitaxel","route":"/drugs/paclitaxel/"}],"term":[{"id":"chemoradiation","kind":"term","name":"Chemoradiation (chemoradiotherapy, CRT)","route":"/terms/chemoradiation/"},{"id":"gej","kind":"term","name":"Gastro-oesophageal junction (GEJ)","route":"/terms/gej/"},{"id":"neoadjuvant-adjuvant","kind":"term","name":"Neoadjuvant / adjuvant / perioperative","route":"/terms/neoadjuvant-adjuvant/"},{"id":"oesophagectomy","kind":"term","name":"Oesophagectomy","route":"/terms/oesophagectomy/"},{"id":"pcr","kind":"term","name":"Pathologic complete response (pCR)","route":"/terms/pcr/"}],"person":[{"id":"jan-van-lanschot","kind":"person","name":"J. Jan B. van Lanschot","route":"/people/jan-van-lanschot/"},{"id":"kitagawa-yuko","kind":"person","name":"Yuko Kitagawa","route":"/people/kitagawa-yuko/"}],"trial":[{"id":"checkmate-577","kind":"trial","name":"CheckMate 577","route":"/trials/checkmate-577/"},{"id":"sano","kind":"trial","name":"SANO","route":"/trials/sano/"}],"pairing":[{"id":"cross-then-nivolumab","kind":"pairing","name":"CROSS chemoradiation → surgery → adjuvant nivolumab if residual disease","route":"/pairings/cross-then-nivolumab/"}],"idea":[{"id":"idea-organ-preservation-esophageal","kind":"idea","name":"Organ preservation as the default after complete response in oesophageal cancer","route":"/ideas/idea-organ-preservation-esophageal/"}],"bottleneck":[{"id":"b-surgery-radiation-innovation","kind":"bottleneck","name":"Surgery and radiotherapy cure most, get least","route":"/bottlenecks/b-surgery-radiation-innovation/"}],"paper":[{"id":"paper-cross-nejm-2012","kind":"paper","name":"CROSS: preoperative chemoradiotherapy for oesophageal or junctional cancer","route":"/key-papers/paper-cross-nejm-2012/"}],"roadmap":[{"id":"chemotherapy-roadmap","kind":"roadmap","name":"Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs","route":"/roadmaps/chemotherapy-roadmap/"},{"id":"radiation-roadmap","kind":"roadmap","name":"Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH","route":"/roadmaps/radiation-roadmap/"}]}}