# CROSS

Source: https://onco.cc/trials/cross/  
OnCo record `cross` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

OS 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).

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-07
- Registry id: 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)
- Enrolled: 366
- Result: 10-year OS 38% vs 25%; median OS 49.4 vs 24.0 months.
- Outcomes: Overall survival: Chemoradiation + surgery 49.4 months vs Surgery alone 24 months, HR 0.68; Overall survival at 10 years: Chemoradiation + surgery 38 percent vs Surgery alone 25 percent
- Replication: Durable at 10 years; NEO-AEGIS and ESOPEC compared it against perioperative chemotherapy in adenocarcinoma with FLOT favoured in ESOPEC.

## Sources

- NEJM 2012: https://www.nejm.org/doi/full/10.1056/NEJMoa1112088
- 10-year outcomes, JCO 2021: https://ascopubs.org/doi/10.1200/JCO.20.03614

## Connected records

- cancers: [Gastric & gastro-oesophageal junction cancer](https://onco.cc/cancers/gastric/), [Oesophageal and junctional adenocarcinoma](https://onco.cc/cancers/oesophageal-adenocarcinoma/), [Oesophageal cancer](https://onco.cc/cancers/esophageal/), [Oesophageal squamous cell carcinoma](https://onco.cc/cancers/oesophageal-squamous-cell-carcinoma/)
- technologies: [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [Platinum agents](https://onco.cc/technologies/platinum/), [Radiosensitisers](https://onco.cc/technologies/radiosensitisers/)
- drugs: [Carboplatin](https://onco.cc/drugs/carboplatin/), [Paclitaxel / nab-paclitaxel](https://onco.cc/drugs/paclitaxel/)
- terms: [Chemoradiation (chemoradiotherapy, CRT)](https://onco.cc/terms/chemoradiation/), [Gastro-oesophageal junction (GEJ)](https://onco.cc/terms/gej/), [Neoadjuvant / adjuvant / perioperative](https://onco.cc/terms/neoadjuvant-adjuvant/), [Oesophagectomy](https://onco.cc/terms/oesophagectomy/), [Pathologic complete response (pCR)](https://onco.cc/terms/pcr/)
- people: [J. Jan B. van Lanschot](https://onco.cc/people/jan-van-lanschot/), [Yuko Kitagawa](https://onco.cc/people/kitagawa-yuko/)
- trials: [CheckMate 577](https://onco.cc/trials/checkmate-577/), [SANO](https://onco.cc/trials/sano/)
- pairings: [CROSS chemoradiation → surgery → adjuvant nivolumab if residual disease](https://onco.cc/pairings/cross-then-nivolumab/)
- ideas: [Organ preservation as the default after complete response in oesophageal cancer](https://onco.cc/ideas/idea-organ-preservation-esophageal/)
- bottlenecks: [Surgery and radiotherapy cure most, get least](https://onco.cc/bottlenecks/b-surgery-radiation-innovation/)
- key papers: [CROSS: preoperative chemoradiotherapy for oesophageal or junctional cancer](https://onco.cc/key-papers/paper-cross-nejm-2012/)
- roadmaps: [Chemotherapy roadmap: mustard gas → curative combinations → the warhead inside smarter drugs](https://onco.cc/roadmaps/chemotherapy-roadmap/), [Radiotherapy roadmap: X-rays → shaped beams → fewer fractions, particles and FLASH](https://onco.cc/roadmaps/radiation-roadmap/)

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