A timeline of esophageal cancer

A couple of friends and I wrote a review article on the history of esophageal cancer. The timeline was so interesting I thought I'd share it here, in a place where it can be easily found and updated.

I’ll put a link to the article when it’s published.

For now, I’m not including any references, and this is an abbreviated version. I hope to fix both of these things in the future, with the goal of a definitive, comprehensive list with a clear paper trail (though a list such as this does require some curation - I’m not interested in every small technical advance, only major firsts and practice-changing updates).

As a side note, it would be cool if HemOnc.org had tables (a table? for comparative work?) of all oncologic drug approvals, with dates and indications, for every global approval agency. Maybe with a link to the trial that led to each approval? (It’s not always 1:1 between trial:approval, but would be nice to know for the majority of cases where that pattern holds). It’s a huge task, but would be so useful for clinicians, researchers, and investors. I’m amazed nobody has done this yet, though there are some partial lists that were helpful. HemOnc does have a few wiki entries on dates of drug approvals, but they’re sparse. (It’s not an easy task, particularly for the Chinese approvals - the only definitive source for the Chinese NMPA appears to be a pdf that is in Chinese only. If you read Chinese and would like to help, please shoot me an email - see the contact link above)

If you are several steps ahead and beat me to building the drug approval tables: brava/bravo/brave/bravi, please lmk and I’ll send you a string of happy, grateful emojis, and we can talk about collaboration.

Likewise, if you know of an important event in esophageal cancer history, have a reference, and think I should add it here, please contact me.

Early History

Key events in the early history of esophageal cancer
Date Event Notes
3000 BCE First description of esophageal surgery, written in Egypt. Smith Surgical Papyrus.
0 BCE First description of EC, written in China. Epidemiologic links to EC described between alcohol, hot drinks, and advanced age.
131-200 First descriptions of EC written in the West. Dates are the life of Galen, Roman Greek physician who wrote extensively. Poor prognosis described.
1090 - 1162 First palliative methods for EC described, including esophagogastric feeding tubes. Dates are the life of Ibn Zuhr, Arabian physician who described these methods.
1543 First detailed illustrations and descriptions of the upper gastrointestinal tract. Vesalius, De Humanis Corporis Fabrica
1690 First personal description of living with EC. Diary of John Casaubon, English surgeon.
1770 First written Western hypothesis of the epidemiologic link between alcohol and EC. Ernst Gottfried Gyser, Medical inaugural dissertation on the fatal hunger, caused by callous narrowing of the esophagus, with phenomena worthy of attention which are detected in certain abdominal viscera.
1857 First described EC operation. Albrecht Theodor von Middeldorph, Breslau surgeon.
1868 Esophagoscope invented. Adolf Kussmaul, German surgeon.
1872 First known esophagectomy. Christian Billroth, Austrian surgeon, with Vincenz Czerny assisting.
1877 First known cervical esophagectomy. Vincenz Czerny. Post-operative survival of 15 months.
1913 First known curative EC resection. Franz Torek, United States surgeon. Post-operative survival of 12 years.
1933 First report on a series of EC resections. Tohru Oshawa, Japanese surgeon. 18 resections, 56% mortality.
1947 First large report on a series of EC resections in the West. Richard Sweet, United States surgeon. 213 resections, 17% mortality, 8% 5-year survival.
1959 First report with <10% operative mortality Komei Nakayama, Japanese surgeon. 953 resections, 5.8% mortality.
1981 First report with <5% operative mortality Hiroshi Akiyama, Japanese surgeon. 210 resections, 1.4% mortality, 34.6% 5-year survival.
Acronyms: BCE - Before Common Era. EC - Esophageal Cancer.

Key clinical trials and approvals

Key clinical trials and approvals
1981 First neoadjuvant RT trial for EC Launois et al. 40 Gy. Results were negative.
1984 First neoadjuvant CRT trial for EC Leichman et al. 30 Gy, cisplatin. pCR 37%, operative mortality 27%, no survival benefit.
1988 First perioperative chemotherapy trial for EC Roth et al. No benefit for cohort overall. mOS of responders 20mo, non-responders 6.2mo, surgery alone 8mo.
2002 First whole-cohort positive perioperative chemotherapy trial Lancet, United Kingdom. Cisplatin+fluorouracil. mOS 16.8mo vs 13.3mo for surgery alone.
2010 Trastuzumab shown to have benefit for HER2+ GC and GEJC ToGA trial. Trastuzumab+chemotherapy. mOS 13.8mo vs 11.1mo for chemotherapy alone.
2012 CROSS trial first report Van Hagen et al. 40 Gy, carboplatin+paclitaxel. mOS 49.4mo vs 24.0mo for surgery alone.
2017-09-22 First FDA approval for IO for EGC KEYNOTE-059, pembrolizumab monotherapy, approved for 3rd line. Approval was later withdrawn as pembrolizumab moved to earlier lines.
2019-07-30 First FDA approval for 2nd line IO for EGC KEYNOTE-181, pembrolizumab monotherapy. ESCC with CPS >=10. mOS 8.2mo vs 7.1mo for chemotherapy.
2020-06-10 First FDA approval for 2nd line IO for EGC, agnostic of CPS ATTRACTION-3, nivolumab monotherapy. ESCC. mOS 10.9mo vs 8.4mo for chemotherapy.
2020-06-19 First NMPA approval for locally-produced IO, 2nd line camrelizumab for ESCC ESCORT, camrelizumab monotherapy. ESCC. mOS 8.3mo vs 6.2mo for chemotherapy.
2021-01-15 First FDA approval for antibody drug conjugate in EGC DESTINY-Gastric01, fam-trastuzumab deruxtecan-nxki. EGC, AC, HER2+, 2nd line. mOS 12.5mo vs 8.4mo for chemotherapy.
2021-03-22 First FDA approval for 1st line IO for EGC KEYNOTE-590, pembrolizumab with chemotherapy, EGC, AC and SCC, CPS agnostic. mOS 13.9mo (ESCC w CPS >=10) vs 8.8mo for chemotherapy alone.
2021-04-16 Second FDA approval for 1st line IO for EGC CheckMate 649, nivolumab with chemotherapy, similar setting to KEYNOTE-590. mOS 13.8 vs 11.1mo for chemotherapy alone.
2021-05-05 First FDA approval for 1st line IO + chemotherapy + HER2-targeted therapy KEYNOTE-811, pembrolizumab + trastuzumab + chemotherapy. ORR 74.4% vs 51.9% for trastuzumab + chemotherapy alone. CR 11.3% vs 3.1%, respectively.
2021-05-20 First FDA approval for adjuvant IO monotherapy CheckMate 577, nivolumab after CROSS, EGC, AC and SCC, CPS agnostic. ESCC mDFS 29.7mo vs 11mo for placebo, EAC 19.4mo vs 11mo.
2021-12-10 NMPA approval for 1st line camrelizumab + chemotherapy for ESCC ESCORT-1st, camrelizumab with chemotherapy. mOS 15.3mo vs 12.0mo for chemotherapy alone.
2022-02-21 NMPA approval for 1st line tislelizumab monotherapy for GC and GEJC Based on phase I/II studies.
2022-04-13 NMPA approval for 2nd line tislelizumab monotherapy for ESCC RATIONALE-302, tislelizumab monotherapy vs chemotherapy, ESCC, PD-L1 agnostic. mOS 8.6mo vs 6.3mo for chemotherapy.
2022-05-19 NMPA approval for 1st line tislelizumab + chemotherapy for ESCC RATIONALE-306, tislelizumab with chemotherapy, ESCC, PD-L1 agnostic. mOS 17.2mo vs 10.6mo for chemotherapy alone.
2022-05-27 First FDA approval for 1st line dual IO CheckMate 648, nivolumab with ipilimumab, ESCC, PD-L1 >=1%. mOS 13.2mo for IO + chemotherapy vs 12.8mo for IO + IO vs 10.7mo for chemotherapy alone.
2022-06-20 NMPA approval for 1st line sintilimab + chemotherapy for GC and GEJC, agnostic of CPS. ORIENT-16, sintilimab + chemotherapy vs chemotherapy, AC. For CPS >= 5, mOS 19.2mo vs 12.9mo for chemotherapy alone. For unselected CPS, mOS 15.2mo vs 12.3mo for chemotherapy alone.
2023-01-24 First OS data available for HER2 vaccine therapy HERIZON study, HER-Vaxx (IMU-131)+chemotherapy, metastatic or advanced HER2+ GC and GEJC. mOS 13.9mo for vaccine+chemotherapy vs 8.3mo for chemotherapy alone.
2023-02-24 NMPA approval for 1st line tislelizumab + chemotherapy for GC and GEJC. RATIONALE-305, tislelizumab + chemotherapy vs chemotherapy, AC. For PD-L1 >=5%, mOS 17.2mo for IO + chemotherapy vs 12.6mo for chemotherapy alone.
Acronyms and abbreviations: CPS - combined positive score. (C)RT - (chemo)radiotherapy. (E)AC - (esophageal) adenocarcinoma. EC - Esophageal Cancer. EGC - esophagogastric cancers. (E)SCC - (esophageal) squamous cell carcinoma. FDA - United States Food and Drug Administration.IO - immuno-oncologic therapy. pCR - pathologic complete response. PD-L1 - programmed death-ligand 1.mDFS - median disease-free survival. mo - month(s). mOS - median overall survival. NMPA - China’s National Medical Products Administration. ORR - overall response rate.