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Published in: Annals of Surgical Oncology 2/2021

01-02-2021 | Gastric Cancer | Gastrointestinal Oncology

Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer

Authors: Denslow A. Trumbull, BS, Riccardo Lemini, MD, Tamara Díaz Vico, MD, Matthew S. Jorgensen, BS, Kristopher Attwood, PhD, Wenyan Ji, MA, Maureen Brady, PA, Emmanuel Gabriel, MD, PhD, Moshim Kukar, MD

Published in: Annals of Surgical Oncology | Issue 2/2021

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Abstract

Background

Few studies have compared the survival advantage of complete pathologic response (cPR) achieved through neoadjuvant chemotherapy (nCT) versus neoadjuvant chemoradiotherapy (nCRT) in gastric adenocarcinoma. Our study utilizes a large national cancer database to address this question.

Patients and Methods

This is a retrospective review of patients with clinical stage I to III gastric adenocarcinoma from 2004 to 2013 who received nCT or nCRT. Patients who achieved cPR were selected. Associations were evaluated using Mann–Whitney U and Fisher’s exact tests. Survival information was summarized using standard Kaplan–Meier methods, where estimates of the median and 5-year survival rates were estimated with 95% confidence intervals.

Results

A total of 413 patients who had cPR were identified. Eighty-four patients received nCT and 329 patients received nCRT. Patients in the nCRT group had higher clinical stage (88.4% vs. 75.0%) and more proximal location of tumors (95.4% vs. 45.2%). The nCT group (n = 84) had a 94% 5-year survival rate, while the nCRT group’s (n = 329) rate was 60% (p < 0.001). On Cox regression modeling using a propensity-weighted approach, nCT treatment was an independent predictor of improved overall survival (nCRT vs. nCT; HR 10.44, p < 0.001).

Conclusions

The use of nCT leads to a significant increase in overall survival in patients when compared with nCRT for those who achieved cPR in gastric adenocarcinoma. While this study is limited in identifying the cause for this difference in overall survival, this important finding nonetheless requires further investigation and should be considered in the development of future gastric cancer trials.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:359–86.CrossRef Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:359–86.CrossRef
3.
go back to reference Spiegel D, Palta M, Uronis H. Role of chemotherapy and radiation therapy in the management of gastric adenocarcinoma. Surg Clin North Am. 2017;97:421–35.CrossRef Spiegel D, Palta M, Uronis H. Role of chemotherapy and radiation therapy in the management of gastric adenocarcinoma. Surg Clin North Am. 2017;97:421–35.CrossRef
4.
go back to reference Cai Z, Yin Y, Shen C, et al. Comparative effectiveness of preoperative, postoperative and perioperative treatments for resectable gastric cancer: a network meta-analysis of the literature from the past 20 years. Surg Oncol. 2018;27:563–74.CrossRef Cai Z, Yin Y, Shen C, et al. Comparative effectiveness of preoperative, postoperative and perioperative treatments for resectable gastric cancer: a network meta-analysis of the literature from the past 20 years. Surg Oncol. 2018;27:563–74.CrossRef
6.
go back to reference Cats A, Jansen EPM, van Grieken N, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19:616–28.CrossRef Cats A, Jansen EPM, van Grieken N, et al. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018;19:616–28.CrossRef
7.
go back to reference Hizal M, Sendur MA, Bilgin B, Bulent Akinci M, Sener Dede D, Yalcin B. Expanding treatment options for resectable gastric cancer: is it a countdown for radiotherapy? J BUON. 2019;24:1367–70.PubMed Hizal M, Sendur MA, Bilgin B, Bulent Akinci M, Sener Dede D, Yalcin B. Expanding treatment options for resectable gastric cancer: is it a countdown for radiotherapy? J BUON. 2019;24:1367–70.PubMed
8.
go back to reference Lane WO, Nussbaum DP, Sun Z, Blazer DG. Preoperative radiation therapy in the surgical management of gastric and junctional adenocarcinoma: should lymph node retrieval guidelines be altered? J Surg Oncol. 2018;117:1708–15.CrossRef Lane WO, Nussbaum DP, Sun Z, Blazer DG. Preoperative radiation therapy in the surgical management of gastric and junctional adenocarcinoma: should lymph node retrieval guidelines be altered? J Surg Oncol. 2018;117:1708–15.CrossRef
9.
go back to reference Newton AD, Datta J, Loaiza-Bonilla A, Karakousis GC, Roses RE. Neoadjuvant therapy for gastric cancer: current evidence and future directions. J Gastrointest Oncol. 2015;6:534–43.PubMedPubMedCentral Newton AD, Datta J, Loaiza-Bonilla A, Karakousis GC, Roses RE. Neoadjuvant therapy for gastric cancer: current evidence and future directions. J Gastrointest Oncol. 2015;6:534–43.PubMedPubMedCentral
10.
go back to reference Ott K, Sendler A, Becker K, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6:159–67.CrossRef Ott K, Sendler A, Becker K, et al. Neoadjuvant chemotherapy with cisplatin, 5-FU, and leucovorin (PLF) in locally advanced gastric cancer: a prospective phase II study. Gastric Cancer. 2003;6:159–67.CrossRef
11.
go back to reference Valenti V, Hernandez-Lizoaín JL, Beorlegui MC, et al. Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy. J Surg Oncol. 2011;104:124–9.CrossRef Valenti V, Hernandez-Lizoaín JL, Beorlegui MC, et al. Morbidity, mortality, and pathological response in patients with gastric cancer preoperatively treated with chemotherapy or chemoradiotherapy. J Surg Oncol. 2011;104:124–9.CrossRef
12.
go back to reference Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRef Cunningham D, Allum WH, Stenning SP, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006;355:11–20.CrossRef
13.
go back to reference Adams S, Chakravarthy AB, Donach M, et al. Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival. Breast Cancer Res Treat. 2010;124:723–32.CrossRef Adams S, Chakravarthy AB, Donach M, et al. Preoperative concurrent paclitaxel-radiation in locally advanced breast cancer: pathologic response correlates with five-year overall survival. Breast Cancer Res Treat. 2010;124:723–32.CrossRef
14.
go back to reference Chavez-MacGregor M, Litton J, Chen H, et al. Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: evaluating the effect of race/ethnicity. Cancer. 2010;116:4168–77.CrossRef Chavez-MacGregor M, Litton J, Chen H, et al. Pathological complete response in breast cancer patients receiving anthracycline and taxane-based neoadjuvant chemotherapy: evaluating the effect of race/ethnicity. Cancer. 2010;116:4168–77.CrossRef
15.
go back to reference Park JW, Kim JH, Choi EK, et al. Prognosis of esophageal cancer patients with pathologic complete response after preoperative concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;81:691–7.CrossRef Park JW, Kim JH, Choi EK, et al. Prognosis of esophageal cancer patients with pathologic complete response after preoperative concurrent chemoradiotherapy. Int J Radiat Oncol Biol Phys. 2011;81:691–7.CrossRef
16.
go back to reference Alnaji RM, Du W, Gabriel E, et al. Pathologic complete response is an independent predictor of improved survival following neoadjuvant chemoradiation for esophageal adenocarcinoma. J Gastrointest Surg. 2016;20:1541–6.CrossRef Alnaji RM, Du W, Gabriel E, et al. Pathologic complete response is an independent predictor of improved survival following neoadjuvant chemoradiation for esophageal adenocarcinoma. J Gastrointest Surg. 2016;20:1541–6.CrossRef
17.
go back to reference Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44.CrossRef Maas M, Nelemans PJ, Valentini V, et al. Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol. 2010;11:835–44.CrossRef
18.
go back to reference Li Z, Shan F, Wang Y, et al. Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis. PLoS ONE. 2018;13:0189294. Li Z, Shan F, Wang Y, et al. Correlation of pathological complete response with survival after neoadjuvant chemotherapy in gastric or gastroesophageal junction cancer treated with radical surgery: A meta-analysis. PLoS ONE. 2018;13:0189294.
19.
go back to reference Cho H, Nakamura J, Asaumi Y, et al. Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature. Ann Surg Oncol. 2015;22:787–92.CrossRef Cho H, Nakamura J, Asaumi Y, et al. Long-term survival outcomes of advanced gastric cancer patients who achieved a pathological complete response with neoadjuvant chemotherapy: a systematic review of the literature. Ann Surg Oncol. 2015;22:787–92.CrossRef
20.
go back to reference Badgwell B, Blum M, Estrella J, et al. Predictors of survival in patients with resectable gastric cancer treated with preoperative chemoradiation therapy and gastrectomy. J Am Coll Surg. 2015;221:83–90.CrossRef Badgwell B, Blum M, Estrella J, et al. Predictors of survival in patients with resectable gastric cancer treated with preoperative chemoradiation therapy and gastrectomy. J Am Coll Surg. 2015;221:83–90.CrossRef
21.
go back to reference Fields RC, Strong VE, Gönen M, et al. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer. 2011;104:1840–7.CrossRef Fields RC, Strong VE, Gönen M, et al. Recurrence and survival after pathologic complete response to preoperative therapy followed by surgery for gastric or gastrooesophageal adenocarcinoma. Br J Cancer. 2011;104:1840–7.CrossRef
22.
go back to reference Ajani JA, Mansfield PF, Crane CH, et al. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005;23:1237–44.CrossRef Ajani JA, Mansfield PF, Crane CH, et al. Paclitaxel-based chemoradiotherapy in localized gastric carcinoma: degree of pathologic response and not clinical parameters dictated patient outcome. J Clin Oncol. 2005;23:1237–44.CrossRef
23.
go back to reference Ajani JA, Mansfield PF, Janjan N, et al. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol. 2004;22:2774–80.CrossRef Ajani JA, Mansfield PF, Janjan N, et al. Multi-institutional trial of preoperative chemoradiotherapy in patients with potentially resectable gastric carcinoma. J Clin Oncol. 2004;22:2774–80.CrossRef
24.
go back to reference Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24:3953–8.CrossRef Ajani JA, Winter K, Okawara GS, et al. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006;24:3953–8.CrossRef
25.
go back to reference Al-Batran S-E, Hofheinz RD, Pauligk C, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016;17:1697–708.CrossRef Al-Batran S-E, Hofheinz RD, Pauligk C, et al. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016;17:1697–708.CrossRef
26.
go back to reference Trip AK, Poppema BJ, van Berge Henegouwen MI, et al. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study. Radiother Oncol. 2014;112:284–8.CrossRef Trip AK, Poppema BJ, van Berge Henegouwen MI, et al. Preoperative chemoradiotherapy in locally advanced gastric cancer, a phase I/II feasibility and efficacy study. Radiother Oncol. 2014;112:284–8.CrossRef
27.
go back to reference Martin-Romano P, Sola JJ, Diaz-Gonzalez JA, et al. Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer. Br J Cancer. 2016;115:655–63.CrossRef Martin-Romano P, Sola JJ, Diaz-Gonzalez JA, et al. Role of histological regression grade after two neoadjuvant approaches with or without radiotherapy in locally advanced gastric cancer. Br J Cancer. 2016;115:655–63.CrossRef
28.
go back to reference Zhang Y, Peng Z, Chen L. Survival analysis of gastric cancer cases with pathological complete response received neoadjuvant chemotherapy. Zhonghua Yi Xue Za Zhi. 2016;96:1582–4.PubMed Zhang Y, Peng Z, Chen L. Survival analysis of gastric cancer cases with pathological complete response received neoadjuvant chemotherapy. Zhonghua Yi Xue Za Zhi. 2016;96:1582–4.PubMed
29.
go back to reference Stark AP, Ikoma N, Chiang YJ, et al. Characteristics and survival of gastric cancer patients with pathologic complete response to preoperative therapy. Ann Surg Oncol. 2019;26:3602–10.CrossRef Stark AP, Ikoma N, Chiang YJ, et al. Characteristics and survival of gastric cancer patients with pathologic complete response to preoperative therapy. Ann Surg Oncol. 2019;26:3602–10.CrossRef
30.
go back to reference Spolverato G, Ejaz A, Kim Y, et al. Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis. J Am Coll Surg. 2014;219:664–75.CrossRef Spolverato G, Ejaz A, Kim Y, et al. Rates and patterns of recurrence after curative intent resection for gastric cancer: a United States multi-institutional analysis. J Am Coll Surg. 2014;219:664–75.CrossRef
31.
go back to reference Nakagawa M, Kojima K, Inokuchi M, et al. Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy: reliable results following long-term follow-up. Eur J Surg Oncol. 2014;40:1376–82.CrossRef Nakagawa M, Kojima K, Inokuchi M, et al. Patterns, timing and risk factors of recurrence of gastric cancer after laparoscopic gastrectomy: reliable results following long-term follow-up. Eur J Surg Oncol. 2014;40:1376–82.CrossRef
32.
go back to reference Wong RKS, Jang R, Darling G. Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy. J Gastrointest Oncol. 2015;6:89–107.PubMedPubMedCentral Wong RKS, Jang R, Darling G. Postoperative chemoradiotherapy vs. preoperative chemoradiotherapy for locally advanced (operable) gastric cancer: clarifying the role and technique of radiotherapy. J Gastrointest Oncol. 2015;6:89–107.PubMedPubMedCentral
33.
go back to reference Fujitani K, Ajani JA, Crane CH, et al. Impact of induction chemotherapy and preoperative chemoradiotherapy on operative morbidity and mortality in patients with locoregional adenocarcinoma of the stomach or gastroesophageal junction. Ann Surg Oncol. 2007;14:2010–7.CrossRef Fujitani K, Ajani JA, Crane CH, et al. Impact of induction chemotherapy and preoperative chemoradiotherapy on operative morbidity and mortality in patients with locoregional adenocarcinoma of the stomach or gastroesophageal junction. Ann Surg Oncol. 2007;14:2010–7.CrossRef
34.
go back to reference Slagter AE, Jansen EPM, van Laarhoven HWM, et al. CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer. 2018;18:877.CrossRef Slagter AE, Jansen EPM, van Laarhoven HWM, et al. CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer. BMC Cancer. 2018;18:877.CrossRef
35.
go back to reference Leong T, Smithers BM, Michael M, et al. TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG). BMC Cancer. 2015;15:532.CrossRef Leong T, Smithers BM, Michael M, et al. TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG). BMC Cancer. 2015;15:532.CrossRef
36.
go back to reference Leong T, Smithers BM, Haustermans K, et al. TOPGEAR: a randomized, phase III trial of perioperative ECF chemotherapy with or without preoperative chemoradiation for resectable gastric cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol. 2017;24:2252–8.CrossRef Leong T, Smithers BM, Haustermans K, et al. TOPGEAR: a randomized, phase III trial of perioperative ECF chemotherapy with or without preoperative chemoradiation for resectable gastric cancer: interim results from an international, intergroup trial of the AGITG, TROG, EORTC and CCTG. Ann Surg Oncol. 2017;24:2252–8.CrossRef
37.
go back to reference Amini N, Spolverato G, Kim Y, et al. Clinicopathological features and prognosis of gastric cardia adenocarcinoma: a multi-institutional U.S. study. J Surg Oncol. 2015;111:285–92.CrossRef Amini N, Spolverato G, Kim Y, et al. Clinicopathological features and prognosis of gastric cardia adenocarcinoma: a multi-institutional U.S. study. J Surg Oncol. 2015;111:285–92.CrossRef
38.
go back to reference Zhao J, Zhao J, Du F, et al. Cardia and non-cardia gastric cancer have similar stage-for-stage prognoses after R0 resection: a large-scale, multicenter study in China. J Gastrointest Surg. 2016;20:700–7.CrossRef Zhao J, Zhao J, Du F, et al. Cardia and non-cardia gastric cancer have similar stage-for-stage prognoses after R0 resection: a large-scale, multicenter study in China. J Gastrointest Surg. 2016;20:700–7.CrossRef
Metadata
Title
Prognostic Significance of Complete Pathologic Response Obtained with Chemotherapy Versus Chemoradiotherapy in Gastric Cancer
Authors
Denslow A. Trumbull, BS
Riccardo Lemini, MD
Tamara Díaz Vico, MD
Matthew S. Jorgensen, BS
Kristopher Attwood, PhD
Wenyan Ji, MA
Maureen Brady, PA
Emmanuel Gabriel, MD, PhD
Moshim Kukar, MD
Publication date
01-02-2021
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 2/2021
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08921-9

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