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1 <!DOCTYPE html> 2 <html lang="en"> 3 <head> 4 <link rel="stylesheet" href="/style.css" type="text/css"> 5 <meta charset="utf-8"> 6 <meta http-equiv="Content-Type" content="text/html; charset=utf-8"> 7 <meta name="viewport" content="width=device-width, initial-scale=1.0"> 8 <link rel="stylesheet" type="text/css" href="/style.css"> 9 <link rel="icon" href="data:image/svg+xml,<svg xmlns=%22http://www.w3.org/2000/svg%22 viewBox=%220 0 100 100%22><text y=%22.9em%22 font-size=%2290%22>🏕️</text></svg>"> 10 <title></title> 11 </head> 12 <body> 13 <div id="page-wrapper"> 14 <div id="header" role="banner"> 15 <header class="banner"> 16 <div id="banner-text"> 17 <span class="banner-title"><a href="/">beauhilton</a></span> 18 </div> 19 </header> 20 <nav> 21 <a href="/about">about</a> 22 <a href="/now">now</a> 23 <a href="/thanks">thanks</a> 24 <a class="nav-active" href="/posts">posts</a> 25 <a href="https://notes.beauhilton.com">notes</a> 26 <a href="https://talks.beauhilton.com">talks</a> 27 <a href="https://git.beauhilton.com">git</a> 28 <a href="/contact">contact</a> 29 <a href="/atom.xml">rss</a> 30 </nav> 31 </div> 32 <main> 33 <h1> 34 A timeline of esophageal cancer 35 </h1> 36 <p> 37 <time id="post-date">2023-10-20</time> 38 </p> 39 <p id="post-excerpt"> 40 A couple of friends and I wrote a review article on the history of esophageal cancer. 41 The timeline was so interesting I thought I'd share it here, in a place where it can be easily found and updated. 42 </p> 43 <p> 44 I’ll put a link to the article when it’s published. 45 </p> 46 <p> 47 For now, I’m not including any references, and this is an abbreviated 48 version. I hope to fix both of these things in the future, with the goal 49 of a definitive, comprehensive list with a clear paper trail (though a 50 list such as this does require some curation - I’m not interested in 51 every small technical advance, only major firsts and practice-changing 52 updates). 53 </p> 54 <p> 55 As a side note, it would be cool if <a href="hemonc.org">HemOnc.org</a> had tables (<em>a</em> table? for 56 comparative work?) of all oncologic drug approvals, with dates and 57 indications, for every global approval agency. Maybe with a link to the 58 trial that led to each approval? (It’s not always 1:1 between 59 trial:approval, but would be nice to know for the majority of cases 60 where that pattern holds). It’s a huge task, but would be so useful for 61 clinicians, researchers, and investors. I’m amazed nobody has done this 62 yet, though there are some partial lists that were helpful. HemOnc does 63 have a few wiki entries on dates of drug approvals, but they’re sparse. 64 (It’s not an easy task, particularly for the Chinese approvals - the 65 only definitive source for the Chinese NMPA appears to be a pdf that is 66 in Chinese only. If you read Chinese and would like to help, please 67 shoot me an email - see the contact link above) 68 </p> 69 <p> 70 If you are several steps ahead and beat me to building the drug 71 approval tables: brava/bravo/brave/bravi, please lmk and I’ll send you a 72 string of happy, grateful emojis, and we can talk about 73 collaboration. 74 </p> 75 <p> 76 Likewise, if you know of an important event in esophageal cancer 77 history, have a reference, and think I should add it here, please 78 contact me. 79 </p> 80 <h2> 81 Early History 82 </h2> 83 <table> 84 <thead> 85 <tr> 86 <th colspan="3"> 87 Key events in the early history of esophageal cancer 88 </th> 89 </tr> 90 </thead> 91 <tbody> 92 <tr> 93 <td> 94 Date 95 </td> 96 <td> 97 Event 98 </td> 99 <td> 100 Notes 101 </td> 102 </tr> 103 <tr> 104 <td> 105 3000 BCE 106 </td> 107 <td> 108 First description of esophageal surgery, written in Egypt. 109 </td> 110 <td> 111 Smith Surgical Papyrus. 112 </td> 113 </tr> 114 <tr> 115 <td> 116 0 BCE 117 </td> 118 <td> 119 First description of EC, written in China. 120 </td> 121 <td> 122 Epidemiologic links to EC described between alcohol, hot drinks, and advanced age. 123 </td> 124 </tr> 125 <tr> 126 <td> 127 131-200 128 </td> 129 <td> 130 First descriptions of EC written in the West. 131 </td> 132 <td> 133 Dates are the life of Galen, Roman Greek physician who wrote extensively. Poor prognosis described. 134 </td> 135 </tr> 136 <tr> 137 <td> 138 1090 - 1162 139 </td> 140 <td> 141 First palliative methods for EC described, including esophagogastric feeding tubes. 142 </td> 143 <td> 144 Dates are the life of Ibn Zuhr, Arabian physician who described these methods. 145 </td> 146 </tr> 147 <tr> 148 <td> 149 1543 150 </td> 151 <td> 152 First detailed illustrations and descriptions of the upper gastrointestinal tract. 153 </td> 154 <td> 155 Vesalius, <i>De Humanis Corporis Fabrica</i> 156 </td> 157 </tr> 158 <tr> 159 <td> 160 1690 161 </td> 162 <td> 163 First personal description of living with EC. 164 </td> 165 <td> 166 Diary of John Casaubon, English surgeon. 167 </td> 168 </tr> 169 <tr> 170 <td> 171 1770 172 </td> 173 <td> 174 First written Western hypothesis of the epidemiologic link between alcohol and EC. 175 </td> 176 <td> 177 Ernst Gottfried Gyser, <i>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.</i> 178 </td> 179 </tr> 180 <tr> 181 <td> 182 1857 183 </td> 184 <td> 185 First described EC operation. 186 </td> 187 <td> 188 Albrecht Theodor von Middeldorph, Breslau surgeon. 189 </td> 190 </tr> 191 <tr> 192 <td> 193 1868 194 </td> 195 <td> 196 Esophagoscope invented. 197 </td> 198 <td> 199 Adolf Kussmaul, German surgeon. 200 </td> 201 </tr> 202 <tr> 203 <td> 204 1872 205 </td> 206 <td> 207 First known esophagectomy. 208 </td> 209 <td> 210 Christian Billroth, Austrian surgeon, with Vincenz Czerny assisting. 211 </td> 212 </tr> 213 <tr> 214 <td> 215 1877 216 </td> 217 <td> 218 First known cervical esophagectomy. 219 </td> 220 <td> 221 Vincenz Czerny. Post-operative survival of 15 months. 222 </td> 223 </tr> 224 <tr> 225 <td> 226 1913 227 </td> 228 <td> 229 First known curative EC resection. 230 </td> 231 <td> 232 Franz Torek, United States surgeon. Post-operative survival of 12 years. 233 </td> 234 </tr> 235 <tr> 236 <td> 237 1933 238 </td> 239 <td> 240 First report on a series of EC resections. 241 </td> 242 <td> 243 Tohru Oshawa, Japanese surgeon. 18 resections, 56% mortality. 244 </td> 245 </tr> 246 <tr> 247 <td> 248 1947 249 </td> 250 <td> 251 First large report on a series of EC resections in the West. 252 </td> 253 <td> 254 Richard Sweet, United States surgeon. 213 resections, 17% mortality, 8% 5-year survival. 255 </td> 256 </tr> 257 <tr> 258 <td> 259 1959 260 </td> 261 <td> 262 First report with <10% operative mortality 263 </td> 264 <td> 265 Komei Nakayama, Japanese surgeon. 953 resections, 5.8% mortality. 266 </td> 267 </tr> 268 <tr> 269 <td> 270 1981 271 </td> 272 <td> 273 First report with <5% operative mortality 274 </td> 275 <td> 276 Hiroshi Akiyama, Japanese surgeon. 210 resections, 1.4% mortality, 34.6% 5-year survival. 277 </td> 278 </tr> 279 <tr> 280 <td colspan="3"> 281 Acronyms: BCE - Before Common Era. EC - Esophageal Cancer. 282 </td> 283 </tr> 284 </tbody> 285 </table> 286 <h2> 287 Key clinical trials and approvals 288 </h2> 289 <table> 290 <thead> 291 <tr> 292 <th colspan="3"> 293 Key clinical trials and approvals 294 </th> 295 </tr> 296 </thead> 297 <tbody> 298 <tr> 299 <td> 300 1981 301 </td> 302 <td> 303 First neoadjuvant RT trial for EC 304 </td> 305 <td> 306 Launois et al. 40 Gy. Results were negative. 307 </td> 308 </tr> 309 <tr> 310 <td> 311 1984 312 </td> 313 <td> 314 First neoadjuvant CRT trial for EC 315 </td> 316 <td> 317 Leichman et al. 30 Gy, cisplatin. pCR 37%, operative mortality 27%, no survival benefit. 318 </td> 319 </tr> 320 <tr> 321 <td> 322 1988 323 </td> 324 <td> 325 First perioperative chemotherapy trial for EC 326 </td> 327 <td> 328 Roth et al. No benefit for cohort overall. mOS of responders 20mo, non-responders 6.2mo, surgery alone 8mo. 329 </td> 330 </tr> 331 <tr> 332 <td> 333 2002 334 </td> 335 <td> 336 First whole-cohort positive perioperative chemotherapy trial 337 </td> 338 <td> 339 Lancet, United Kingdom. Cisplatin+fluorouracil. mOS 16.8mo vs 13.3mo for surgery alone. 340 </td> 341 </tr> 342 <tr> 343 <td> 344 2010 345 </td> 346 <td> 347 Trastuzumab shown to have benefit for HER2+ GC and GEJC 348 </td> 349 <td> 350 ToGA trial. Trastuzumab+chemotherapy. mOS 13.8mo vs 11.1mo for chemotherapy alone. 351 </td> 352 </tr> 353 <tr> 354 <td> 355 2012 356 </td> 357 <td> 358 CROSS trial first report 359 </td> 360 <td> 361 Van Hagen et al. 40 Gy, carboplatin+paclitaxel. mOS 49.4mo vs 24.0mo for surgery alone. 362 </td> 363 </tr> 364 <tr> 365 <td> 366 2017-09-22 367 </td> 368 <td> 369 First FDA approval for IO for EGC 370 </td> 371 <td> 372 KEYNOTE-059, pembrolizumab monotherapy, approved for 3rd line. Approval was later withdrawn as pembrolizumab moved to earlier lines. 373 </td> 374 </tr> 375 <tr> 376 <td> 377 2019-07-30 378 </td> 379 <td> 380 First FDA approval for 2nd line IO for EGC 381 </td> 382 <td> 383 KEYNOTE-181, pembrolizumab monotherapy. ESCC with CPS >=10. mOS 8.2mo vs 7.1mo for chemotherapy. 384 </td> 385 </tr> 386 <tr> 387 <td> 388 2020-06-10 389 </td> 390 <td> 391 First FDA approval for 2nd line IO for EGC, agnostic of CPS 392 </td> 393 <td> 394 ATTRACTION-3, nivolumab monotherapy. ESCC. mOS 10.9mo vs 8.4mo for chemotherapy. 395 </td> 396 </tr> 397 <tr> 398 <td> 399 2020-06-19 400 </td> 401 <td> 402 First NMPA approval for locally-produced IO, 2nd line camrelizumab for ESCC 403 </td> 404 <td> 405 ESCORT, camrelizumab monotherapy. ESCC. mOS 8.3mo vs 6.2mo for chemotherapy. 406 </td> 407 </tr> 408 <tr> 409 <td> 410 2021-01-15 411 </td> 412 <td> 413 First FDA approval for antibody drug conjugate in EGC 414 </td> 415 <td> 416 DESTINY-Gastric01, fam-trastuzumab deruxtecan-nxki. EGC, AC, HER2+, 2nd line. mOS 12.5mo vs 8.4mo for chemotherapy. 417 </td> 418 </tr> 419 <tr> 420 <td> 421 2021-03-22 422 </td> 423 <td> 424 First FDA approval for 1st line IO for EGC 425 </td> 426 <td> 427 KEYNOTE-590, pembrolizumab with chemotherapy, EGC, AC and SCC, CPS agnostic. mOS 13.9mo (ESCC w CPS >=10) vs 8.8mo for chemotherapy alone. 428 </td> 429 </tr> 430 <tr> 431 <td> 432 2021-04-16 433 </td> 434 <td> 435 Second FDA approval for 1st line IO for EGC 436 </td> 437 <td> 438 CheckMate 649, nivolumab with chemotherapy, similar setting to KEYNOTE-590. mOS 13.8 vs 11.1mo for chemotherapy alone. 439 </td> 440 </tr> 441 <tr> 442 <td> 443 2021-05-05 444 </td> 445 <td> 446 First FDA approval for 1st line IO + chemotherapy + HER2-targeted therapy 447 </td> 448 <td> 449 KEYNOTE-811, pembrolizumab + trastuzumab + chemotherapy. ORR 74.4% vs 51.9% for trastuzumab + chemotherapy alone. CR 11.3% vs 3.1%, respectively. 450 </td> 451 </tr> 452 <tr> 453 <td> 454 2021-05-20 455 </td> 456 <td> 457 First FDA approval for adjuvant IO monotherapy 458 </td> 459 <td> 460 CheckMate 577, nivolumab after CROSS, EGC, AC and SCC, CPS agnostic. ESCC mDFS 29.7mo vs 11mo for placebo, EAC 19.4mo vs 11mo. 461 </td> 462 </tr> 463 <tr> 464 <td> 465 2021-12-10 466 </td> 467 <td> 468 NMPA approval for 1st line camrelizumab + chemotherapy for ESCC 469 </td> 470 <td> 471 ESCORT-1st, camrelizumab with chemotherapy. mOS 15.3mo vs 12.0mo for chemotherapy alone. 472 </td> 473 </tr> 474 <tr> 475 <td> 476 2022-02-21 477 </td> 478 <td> 479 NMPA approval for 1st line tislelizumab monotherapy for GC and GEJC 480 </td> 481 <td> 482 Based on phase I/II studies. 483 </td> 484 </tr> 485 <tr> 486 <td> 487 2022-04-13 488 </td> 489 <td> 490 NMPA approval for 2nd line tislelizumab monotherapy for ESCC 491 </td> 492 <td> 493 RATIONALE-302, tislelizumab monotherapy vs chemotherapy, ESCC, PD-L1 agnostic. mOS 8.6mo vs 6.3mo for chemotherapy. 494 </td> 495 </tr> 496 <tr> 497 <td> 498 2022-05-19 499 </td> 500 <td> 501 NMPA approval for 1st line tislelizumab + chemotherapy for ESCC 502 </td> 503 <td> 504 RATIONALE-306, tislelizumab with chemotherapy, ESCC, PD-L1 agnostic. mOS 17.2mo vs 10.6mo for chemotherapy alone. 505 </td> 506 </tr> 507 <tr> 508 <td> 509 2022-05-27 510 </td> 511 <td> 512 First FDA approval for 1st line dual IO 513 </td> 514 <td> 515 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. 516 </td> 517 </tr> 518 <tr> 519 <td> 520 2022-06-20 521 </td> 522 <td> 523 NMPA approval for 1st line sintilimab + chemotherapy for GC and GEJC, agnostic of CPS. 524 </td> 525 <td> 526 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. 527 </td> 528 </tr> 529 <tr> 530 <td> 531 2023-01-24 532 </td> 533 <td> 534 First OS data available for HER2 vaccine therapy 535 </td> 536 <td> 537 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. 538 </td> 539 </tr> 540 <tr> 541 <td> 542 2023-02-24 543 </td> 544 <td> 545 NMPA approval for 1st line tislelizumab + chemotherapy for GC and GEJC. 546 </td> 547 <td> 548 RATIONALE-305, tislelizumab + chemotherapy vs chemotherapy, AC. For PD-L1 >=5%, mOS 17.2mo for IO + chemotherapy vs 12.6mo for chemotherapy alone. 549 </td> 550 </tr> 551 <tr> 552 <td colspan="3"> 553 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. 554 </td> 555 </tr> 556 </tbody> 557 </table> 558 </main> 559 <div id="footnotes"></div> 560 <footer></footer> 561 </div> 562 </body> 563 </html>