Index Note: Page numbers of article titles are in boldface type. A Adaptive therapy, for locally advanced gastroesophageal cancers, 447 Adenocarcinoma, emerging novel therapeutic agents for gastroesophageal and gastric, 529 544 cancer stem cells, 533 539 signal transducers and activators of transcription 3 (STAT3) inhibitors, 533 539 CLDN18.2 inhibitors, 539 540 fibroblast growth factor receptor 2 (FGFR2) inhibitors, 530 533 AZD4547, 530 533 resistance to, 533 role in trastuzumab resistance, 533 matrix metalloproteinase (MMP) inhibitors, 540 542 marimastat, 541 specific MMP 9 inhibitors, 541 542 gastroesophageal, targeted therapies for, 511 527 epidermal growth factor receptor, 517 518 ERBB2 (HER2), 512 517 MET, 518 521 intramucosal esophageal, and Barrett s esophagus, 409 426 chemoprevention in, 415 416 NSAIDs, 416 proton pump inhibitors, 415 416 endoscopic surveillance of, 414 epidemiology, genetics, and natural history of, 412 413 eradication of dysplasia and reduction of progression, 416 evaluation of, 414 415 high-grade dysplasia and intramucosal adenocarcinoma, 418 419 low-grade dysplasia, 417 418 management objectives in, 414 415 management of underlying GERD, 415 nondysplastic, 416 417 predictors of progression, 413 414 screening for, 414 Adjuvant therapy, chemoradiation for localized gastric cancer, 458 460 for locally advanced gastroesophageal cancers, 445 446 chemoradiation, 445 446 chemotherapy, 445 446 Anatomic location, of gastroesophageal cancers, impact on management, 442 443 Antiangiogenic therapy, in gastroesophageal cancer, 499 510 angiogenesis pathway, 500 inhibitors of VEGF axis via monoclonal antibodies, 500 504 anti-vegf monoclonal antibody, 500 503 Hematol Oncol Clin N Am 31 (2017) 553 563 http://dx.doi.org/10.1016/s0889-8588(17)30045-x 0889-8588/17 hemonc.theclinics.com
554 Index Antiangiogenic (continued) anti-vegfr2 monoclonal antibody, 503 504 locally advanced disease, 505 ongoing areas of research, 505 507 combination with anti-her2 therapy, 506 combination with immune checkpoint therapy, 505 506 predictive biomarkers, 506 507 tyrosine kinase inhibition of VEGF axis, 504 apatinib in third-line therapy, 504 regorafenib in second/third-line therapy, 504 Apatinib, for gastroesophageal cancer therapy, 504 Archaea, in gastric microbiome, 394 Avelumab, efficacy in gastroesophageal cancer management, 490 491 AZD4547, novel therapy for gastroesophageal and gastric adenocarcinomas, 530 533 B Bacteria. See also Microbiome. esophageal, 391 392 gastric, 390 391 Barrett esophagus, and intramucosal esophageal adenocarcinoma, 409 426 chemoprevention in, 415 416 NSAIDs, 416 proton pump inhibitors, 415 416 endoscopic surveillance of, 414 epidemiology, genetics, and natural history of, 412 413 eradication of dysplasia and reduction of progression, 416 evaluation of, 414 415 high-grade dysplasia and intramucosal adenocarcinoma, 418 419 low-grade dysplasia, 417 418 management objectives in, 414 415 management of underlying GERD, 415 nondysplastic, 416 417 predictors of progression, 413 414 screening for, 414 Biomarkers, predictive, for gastroesophageal cancers, 506 507 C Cancer stem cells, in novel therapies for gastroesophageal and gastric adenocarcinomas, 533 539 Carcinogenesis, gastric, influence of gastric microbiome on, 389 408 community dynamics and pathobionts, 399 401 diversity of along the GI tract, 390 394 archaea, 393 esophageal bacteria, 391 392 fungi, 393 394 gastric bacteria, 390 391 viruses, 392 393 epidemiologic associations with diseases, 395 396 Epstein-Barr virus, 396
Helicobacter pylori, 395 396 other, 396 evidence for microbiome shifts with prior Helicobacter pylori infection, 397 399 Epstein-Barr virus, 398 Fusobacterium sp, 399 other species, 399 identification methodologies from clinical samples, 394 395 computational identification, 394 395 experimental approaches, 394 molecular associations and mechanisms of carcinogenesis, 396 397 Helicobacter pylori tumorigenicity, 396 397 Checkpoint inhibitors, evolving role in esophageal cancer management, 483 498 adjuvant studies, 491 494 in combination with antiangiogenic therapy, 505 506 efficacy of CTLA-4 inhibitors, 491 ipilumumab or tremelimumab, 491 efficacy of PD-1/PD-L1 inhibitors, 489 491 avelumab, 490 491 durvalumab, 491 nivolumab, 490 pembrolizumab, 489 490 localized, role of radiotherapy in, in esophageal cancer, 454 458 in gastric cancer, 458 460 locally advanced, management of, 441 452 differences in anatomic location and histology, 442 443 multimodal treatment options, 443 446 options to improve current approaches, 446 447 overview, 442 PD-L1 expression in, 488 predictive biomarkers to guide use of, 488 489 gene signatures, 489 mononuclear inflammatory score, 488 489 PD-L1/PD-L2 status, 488 rationale for investigating, 486 488 chronic inflammation, 487 genomic instability, 487 high somatic burden, 487 infection, 487 488 Chemoradiation, for localized esophageal cancer, 454 458 definitive, 456 458 neoadjuvant, 454 456 for localized gastric cancer, 458 462 adjuvant, 458 460 neoadjuvant, 460 462 for locally advanced gastroesophageal cancers, 444 446 adjuvant, 445 446 preoperative, 444 445 Chemotherapy, for locally advanced gastroesophageal cancers, 443 445 adjuvant, 445 perioperative, 443 444 for metastatic gastric cancer, 469 483 Index 555
556 Index Chemotherapy (continued) first-line chemotherapy, 472 475 fluoropyrimidines, 472 473 for HER2-positive disease, 474 475 platinum compounds, 472 standard regimens, 475 triplet combinations with epirubicin or docetaxel, 473 474 second-line chemotherapy, 475 478 Claudin inhibitors, novel therapy for gastroesophageal and gastric adenocarcinomas, 539 540 CLDN182 inhibitors, novel therapy for gastroesophageal and gastric adenocarcinomas, 539 540 Computerized tomography (CT), for staging esophageal and gastric cancers, 434 435 with positron emission tomography (PET), 435 436 Cytotoxic T-lymphocyte associated-4 inhibitors, efficacy in gastroesophageal cancer management, 491 ipilumumab, 491 tremelimumab, 491 D Doxorubicin, with triplet combinations in first-line chemotherapy for metastatic gastric cancer, 473 474 Durvalumab, efficacy in gastroesophageal cancer management, 491 Dysplasia, eradication of, in Barrett s esophagus, 416 high-grade, in Barrett s esophagus, 418 419 low-grade, in Barrett s esophagus, 417 418 E Endoscopic resection, for staging esophageal and gastric cancers, 431 434 Endoscopic surveillance, of Barrett s esophagus, 414 Endoscopic ultrasound, for staging esophageal and gastric cancers, 431 434 Epidermal growth factor receptor, targeted therapy for gastroesophageal adenocarcinoma, 517 518 Epirubicin, with triplet combinations in first-line chemotherapy for metastatic gastric cancer, 473 474 Epstein-Barr virus, epidemiologic association with gastric diseases, 396, 398 epigenetic alterations, 398 latent infection in gastric epithelial cells, 398 viral micrornas, 398 Esophageal cancers. See also Gastroesophageal cancers. intramucosal adenocarcinoma, Barrett esophagus and, 409 426 chemoprevention in, 415 416 NSAIDs, 416 proton pump inhibitors, 415 416 endoscopic surveillance of, 414 epidemiology, genetics, and natural history of, 412 413 eradication of dysplasia and reduction of progression, 416 evaluation of, 414 415 high-grade dysplasia and intramucosal adenocarcinoma, 418 419
Index 557 low-grade dysplasia, 417 418 management objectives in, 414 415 management of underlying GERD, 415 nondysplastic, 416 417 predictors of progression, 413 414 screening for, 414 staging in, 427 440 cancer of the gastroesophageal junction, 428 431 CT, 434 435 endoscopic ultrasound and endoscopic resection, 431 434 MRI, 435 PET-CT, 435 436 staging laparoscopy, 436 F Fibroblast growth factor receptor 2 (FGFR2) inhibitors, for gastroesophageal and gastric adenocarcinomas, 530 533 AZD4547, 530 533 resistance to, 533 role in traztuzumab resistance, 533 Fluoropyrimidine, in first-line chemotherapy for metastatic gastric cancer, 472 473 Fungi, in gastric microbiome, 394 395 Fusobacterium sp, epidemiologic association with gastric diseases, 399 G Gastric cancers. See also Gastroesophageal cancers. metastatic, management of, 469 483 first-line chemotherapy, 472 475 fluoropyrimidines, 472 473 for HER2-positive disease, 474 475 platinum compounds, 472 standard regimens, 475 triplet combinations with epirubicin or docetaxel, 473 474 second-line chemotherapy, 475 478 special situations, 478 479 metastatectomy, 479 peritonectomy, 479 synchronous metastases, 478 479 treatment goals, 470 472 staging in, 427 440 cancer of the gastroesophageal junction, 428 431 CT, 434 435 endoscopic ultrasound and endoscopic resection, 431 434 MRI, 435 PET-CT, 435 436 staging laparoscopy, 436 Gastric microbiome. See Microbiome, gastric. Gastroesophageal cancers. See also Esophageal cancers and Gastric cancers. antiangiogenic therapy in, 499 510
558 Index Gastroesophageal (continued ) angiogenesis pathway, 500 inhibitors of VEGF axis via monoclonal antibodies, 500 504 anti-vegf monoclonal antibody, 500 503 anti-vegfr2 monoclonal antibody, 503 504 locally advanced disease, 505 ongoing areas of research, 505 507 combination with anti-her2 therapy, 506 combination with immune checkpoint therapy, 505 506 predictive biomarkers, 506 507 tyrosine kinase inhibition of VEGF axis, 504 apatinib in third-line therapy, 504 regorafenib in second/third-line therapy, 504 emerging novel therapeutic agents for gastroesophageal and gastric, 529 544 cancer stem cells, 533 539 signal transducers and activators of transcription 3 (STAT3) inhibitors, 533 539 CLDN18.2 inhibitors, 539 540 fibroblast growth factor receptor 2 (FGFR2) inhibitors, 530 533 AZD4547, 530 533 resistance to, 533 role in trastuzumab resistance, 533 matrix metalloproteinase (MMP) inhibitors, 540 542 marimastat, 541 specific MMP 9 inhibitors, 541 542 evolving role of checkpoint inhibitors in, 483 498 adjuvant studies, 491 494 efficacy of CTLA-4 inhibitors, 491 ipilumumab or tremelimumab, 491 efficacy of PD-1/PD-L1 inhibitors, 489 491 avelumab, 490 491 durvalumab, 491 nivolumab, 490 pembrolizumab, 489 490 localized, role of radiotherapy in, in esophageal cancer, 454 458 in gastric cancer, 458 460 PD-L1 expression in, 488 predictive biomarkers to guide use of, 488 489 gene signatures, 489 mononuclear inflammatory score, 488 489 PD-L1/PD-L2 status, 488 rationale for investigating, 486 488 chronic inflammation, 487 genomic instability, 487 high somatic burden, 487 infection, 487 488 future directions in improving outcomes, 545 553 disease prevention, 546 547 in locally advanced disease, 548 550 application of novel imaging to identify response, 549 550 integration of targeted therapies, 549 molecular classification of disease, 547 548
Index 559 gastroesophageal, targeted therapies for, 511 527 epidermal growth factor receptor, 517 518 ERBB2 (HER2), 512 517 MET, 518 521 localized, role of radiotherapy in, 453 468 emerging technologies, 462 464 image-guided, 462 464 MRI-guided, 462 464 proton therapy, 462 464 in esophageal cancer, definitive chemoradiation, 456 458 neoadjuvant chemoradiation, 454 456 in gastric cancer, adjuvant chemoradiation, 458 460 neoadjuvant chemoradiation, 460 462 locally advanced, management of, 441 452 differences in anatomic location and histology, 442 443 multimodal treatment options, 443 446 adjuvant chemoradiation, 445 446 perioperative chemotherapy, 443 444 preoperative chemoradiation, 444 445 options to improve current approaches, 446 447 adaptive therapy based on early response prediction, 446 optimization by targeted therapy, 447 overview, 442 Gastroesophageal junction, staging of cancer of, 428 Gastroesophageal reflux disease (GERD), management of, in Barrett s esophagus, 415 H Helicobacter pylori, disease prevention and improved outcomes with gastroesophageal cancers, 546 547 epidemiologic association with gastric diseases, 395 396 evidence for prolonged microbiome shifts associated with prior infection with, 397 398 mechanisms of tumorigenicity, 396 397 Histology, of gastroesophageal cancers, impact on management, 442 443 Human epidermal growth factor 2 (HER2), anti-her2 therapy in combination with antiangiogenic therapy, 506 HER2-positive metastatic gastric cancer, first-line chemotherapy for, 474 475 Human papillomavirus (HPV), risk factor for Barrett s esophagus and esophageal adenocarcinoma, 410 I Immune checkpoint therapy. See Checkpoint inhibitors. Immunotherapy. See Antiangiogenic therapy. Ipilimumab, efficacy in gastroesophageal cancer management, 491 L Laparoscopy, staging, for esophageal and gastric cancers, 437 Locally advance gastroesophageal cancers antiangiogenic therapy in, 505
560 Index Locally (continued) future directions in improving outcomes of, 548 550 integration of targeted therapies, 549 novel imaging to identify response, 549 550 management of, 441 452 differences in anatomic location and histology, 442 443 multimodal treatment options, 443 446 adjuvant chemoradiation, 445 446 perioperative chemotherapy, 443 444 preoperative chemoradiation, 444 445 options to improve current approaches, 446 447 adaptive therapy based on early response prediction, 446 optimization by targeted therapy, 447 overview, 442 M Magnetic resonance imaging (MRI), MRI-guided radiation therapy for esophageal and gastric cancers, 462 464 for staging esophageal and gastric cancers, 435 Marimastat, for gastroesophageal and gastric adenocarcinomas, 541 Matrix metalloproteinase (MMP) inhibitors, for gastroesophageal and gastric adenocarcinomas, 540 542 marimastat, 541 specific MMP 9 inhibitors, 541 542 MET protooncogene, in targeted therapies for gastroesophageal adenocarcinoma, 518 521 Metastatectomy, in management of metastatic gastric cancer, 479 Metastatic cancer, gastric, management of, 469 483 first-line chemotherapy, 472 475 fluoropyrimidines, 472 473 for HER2-positive disease, 474 475 platinum compounds, 472 standard regimens, 474 475 triple combinations with epirubicin or docetaxel, 473 474 second-line chemotherapy, 475 478 special situations, 478 479 metastatectomy, 479 peritonectomy, 479 synchronous metastases, 478 479 treatment goals, 470 472 Microbiome, gastric, influence on gastric carcinogenesis, 389 408 community dynamics and pathobionts, 399 401 diversity of along the GI tract, 390 394 archaea, 393 esophageal bacteria, 391 392 fungi, 393 394 gastric bacteria, 390 391 viruses, 392 393 epidemiologic associations with diseases, 395 396 Epstein-Barr virus, 396
Index 561 Helicobacter pylori, 395 396 other, 396 evidence for microbiome shifts with prior Helicobacter pylori infection, 397 399 Epstein-Barr virus, 398 Fusobacterium sp, 399 other species, 399 identification methodologies from clinical samples, 394 395 computational identification, 394 395 experimental approaches, 394 molecular associations and mechanisms of carcinogenesis, 396 397 Helicobacter pylori tumorigenicity, 396 397 Molecular profiling, in improving outcomes with gastroesophageal cancers, 547 548 MRI-guided radiation therapy, for localized esophageal and gastric cancers, 462 464 Multimodal therapy, of locally advanced gastroesophageal cancers, 443 446 N Napabucasin (BBI-608), novel therapy for gastroesophageal and gastric adenocarcinomas, with weekly paclitaxel, 538 539 Neoadjuvant therapy, chemoradiation for localized esophageal cancer, 454 456 chemoradiation for localized gastric cancer, 460 462 chemoradiation for locally advanced gastroesophageal cancers, 444 445 Nivolumab, efficacy in gastroesophageal cancer management, 490 Nonsteroidal antiinflammatory drugs (NSAIDs), for Barrett s esophagus, 416 O Outcomes, with gastroesophageal cancer, future directions in improving, 545 553 disease prevention, 546 547 in locally advanced disease, 548 550 application of novel imaging to identify response, 549 550 integration of targeted therapies, 549 molecular classification of disease, 547 548 P Paclitaxel, weekly, with napabucasin (BBI-608) for gastroesophageal and gastric adenocarcinomas, 538 539 Pembrolizumab, efficacy in gastroesophageal cancer management, 489 490 Peritonectomy, in management of metastatic gastric cancer, 479 Platinum compounds, in first-line chemotherapy for metastatic gastric cancer, 472 Positron emission tomography (PET), with CT for staging esophageal and gastric cancers, 435 436 Prevention, in improving outcomes with gastroesophageal cancers, 546 547 Programmed death ligand 1 (PD-L1), efficacy of PD-1/PD-L1 inhibitors in gastroesophageal cancer, 489 491 avelumab, 490 491 durvalumab, 491 nivolumab, 490 pembrolizumab, 489 490 expression in gastroesophageal cancer, 488
562 Index Programmed (continued) PD-L1/PD-L2 status as predictive biomarker in gastroesophageal cancer, 488 Proton pump inhibitors, for Barrett s esophagus, 415 416 Proton therapy, for localized esophageal and gastric cancers, 462 464 R Radiotherapy, role in localized esophageal and gastric cancer, 453 468 emerging technologies, 462 464 image-guided, 462 464 MRI-guided, 462 464 proton therapy, 462 464 in esophageal cancer, 454 458 definitive chemoradiation, 456 458 neoadjuvant chemoradiation, 454 456 in gastric cancer, 458 460 adjuvant chemoradiation, 458 460 neoadjuvant chemoradiation, 460 462 Regorafenib, for gastroesophageal cancer therapy, 504 Resection, endoscopic, for staging esophageal and gastric cancers, 431 434 S Signal transducers and activators of transcription 3 (STAT3) inhibitors, in novel therapies for gastroesophageal and gastric adenocarcinomas, 533 539 combination of BBI-608 and weekly paclitaxel, 538 539 napabucasin (BBI-608), 538 OPB-31121, 538 OPB-51602, 538 Staging, in esophageal and gastric cancers, 427 440 cancer of the gastroesophageal junction, 428 431 CT, 434 435 endoscopic ultrasound and endoscopic resection, 431 434 MRI, 435 PET-CT, 435 436 staging laparoscopy, 436 Stem cells, cancer, in novel therapies for gastroesophageal and gastric adenocarcinomas, 533 539 Surveillance, endoscopic, of Barrett s esophagus, 414 Synchronous metastases, of gastric cancer, management of, 478 479 T Targeted therapies, for gastroesophageal adenocarcinoma, 511 527 epidermal growth factor receptor, 517 518 ERBB2 (HER2), 512 517 MET, 518 521 for locally advanced gastroesophageal cancers, 447 role in improving outcomes for gastroesophageal cancer, 547 548 Trastuzumab, in targeted therapy of gastroesophageal adenocarcinoma, 512 517 role of FGFR in resistance to, 533
Index 563 Tremelimumab, efficacy in gastroesophageal cancer management, 491 Triplet combinations, in first-line chemotherapy for metastatic gastric cancer, 473 474 Tyrosine kinase inhibition, of VEGF axis, 504 apatinib in third-line therapy, 504 regorafenib in second/third-line therapy, 504 U Ultrasound, endoscopic, for staging esophageal and gastric cancers, 431 434 Upper gastrointestinal malignancies, 389 552 antiangiogenic therapy in, 499 510 Barrett esophagus and intramucosal esophageal adenocarcinoma, 409 426 checkpoint inhibitors role in, 485 498 emerging novel therapeutic agents, 529 544 future directions in improving outcomes of, 545 553 gastric microbiome and gastric carcinogenesis, 389 408 locally advanced gastroesophageal cancer, 441 452 metastatic gastric cancer, 469 483 radiotherapy for localized esophageal and gastric cancer, 453 468 staging in esophageal and gastric cancers, 427 440 targeted therapies for adenocarcinoma, 511 527 V Vascular endothelial growth factor (VEGF) axis, inhibition of via monoclonal antibodies, 500 504 anti-vegf monoclonal antibody, 500 503 anti-vegfr2 monoclonal antibody, 503 504 Viruses, in gastric microbiome, 393 394