Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection.


Journal

Annals of surgical oncology
ISSN: 1534-4681
Titre abrégé: Ann Surg Oncol
Pays: United States
ID NLM: 9420840

Informations de publication

Date de publication:
Aug 2022
Historique:
received: 10 11 2021
accepted: 08 02 2022
pubmed: 11 4 2022
medline: 7 7 2022
entrez: 10 4 2022
Statut: ppublish

Résumé

Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs. We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010-2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR) = 0-1% viability; major (pMajR) = 2-49% viability; minor (pMinR) = 50-99% viability; or mixed (pMixR) = at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adjusted risk of death was evaluated using Cox regression. Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) [log-rank p < 0.001]. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) [log-rank p = 0.002]. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30-0.78 vs. pMinR). One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.

Sections du résumé

BACKGROUND BACKGROUND
Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs.
METHODS METHODS
We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010-2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR) = 0-1% viability; major (pMajR) = 2-49% viability; minor (pMinR) = 50-99% viability; or mixed (pMixR) = at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adjusted risk of death was evaluated using Cox regression.
RESULTS RESULTS
Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) [log-rank p < 0.001]. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) [log-rank p = 0.002]. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30-0.78 vs. pMinR).
CONCLUSIONS CONCLUSIONS
One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.

Identifiants

pubmed: 35397746
doi: 10.1245/s10434-022-11683-1
pii: 10.1245/s10434-022-11683-1
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

5156-5164

Informations de copyright

© 2022. Society of Surgical Oncology.

Références

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33.
doi: 10.3322/caac.21654
Colorectal cancer facts and figures 2020–2022. Available at: https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/colorectal-cancer-facts-and-figures/colorectal-cancer-facts-and-figures-2020-2022.pdf . Accessed 23 Oct 2021.
Fong Y, Kemeny N, Paty P, Blumgart LH, Cohen AM. Treatment of colorectal cancer: hepatic metastasis. Semin Surg Oncol. 1996;12(4):219–52.
doi: 10.1002/(SICI)1098-2388(199607/08)12:4<219::AID-SSU3>3.0.CO;2-8
Khatri VP, Petrelli NJ, Belghiti J. Extending the frontiers of surgical therapy for hepatic colorectal metastases: is there a limit? J Clin Oncol. 2005;23(33):8490–9.
doi: 10.1200/JCO.2004.00.6155
Engstrand J, Nilsson H, Stromberg C, Jonas E, Freedman J. Colorectal cancer liver metastases—a population-based study on incidence, management and survival. BMC Cancer. 2018;18(1):78.
doi: 10.1186/s12885-017-3925-x
Choti MA, Sitzmann JV, Tiburi MF, Sumetchotimetha W, Rangsin R, Schulick RD, et al. Trends in long-term survival following liver resection for hepatic colorectal metastases. Ann Surg. 2002;235(6):759–66.
doi: 10.1097/00000658-200206000-00002
Abdalla EK, Vauthey JN, Ellis LM, Ellis V, Pollock R, Broglio KR, Hess K, Curley SA. Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg. 2004;239(6):818–25 (Discussion 825–817).
doi: 10.1097/01.sla.0000128305.90650.71
Fernandez FG, Drebin JA, Linehan DC, Dehdashti F, Siegel BA, Strasberg SM. Five-year survival after resection of hepatic metastases from colorectal cancer in patients screened by positron emission tomography with f-18 fluorodeoxyglucose (fdg-pet). Ann Surg. 2004;240(3):438–47 (Discussion 447–450).
doi: 10.1097/01.sla.0000138076.72547.b1
Pawlik TM, Scoggins CR, Zorzi D, Abdalla EK, Andres A, Eng C, Curley SA, Loyer EM, Muratore A, Mentha G, et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg. 2005;241(5):715–22 (Discussion 722–714).
doi: 10.1097/01.sla.0000160703.75808.7d
Nikfarjam M, Shereef S, Kimchi ET, Gusani NJ, Jiang Y, Avella DM, et al. Survival outcomes of patients with colorectal liver metastases following hepatic resection or ablation in the era of effective chemotherapy. Ann Surg Oncol. 2009;16(7):1860–7.
doi: 10.1245/s10434-008-0225-3
Allen PJ, Kemeny N, Jarnagin W, DeMatteo R, Blumgart L, Fong Y. Importance of response to neoadjuvant chemotherapy in patients undergoing resection of synchronous colorectal liver metastases. J Gastrointest Surg. 2003;7(1):109–17.
doi: 10.1016/S1091-255X(02)00121-X
Adam R, Delvart V, Pascal G, Valeanu A, Castaing D, Azoulay D, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: A model to predict long-term survival. Ann Surg. 2004;240(4):644–57 (Discussion 657-648).
doi: 10.1097/01.sla.0000141198.92114.f6
Parikh AA, Robinson J, Zaydfudim VM, Penson D, Whiteside MA. The effect of health insurance status on the treatment and outcomes of patients with colorectal cancer. J Surg Oncol. 2014;110(3):227–32.
doi: 10.1002/jso.23627
Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma Clinicopathologic correlations. Cancer. 1994;73(11):2680–6.
doi: 10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C
Swisher SG, Hofstetter W, Wu TT, Correa AM, Ajani JA, Komaki RR, et al. Proposed revision of the esophageal cancer staging system to accommodate pathologic response (pp) following preoperative chemoradiation (crt). Ann Surg. 2005;241(5):810–7 (Discussion 817-820).
doi: 10.1097/01.sla.0000161983.82345.85
Ajani JA, Mansfield PF, Crane CH, Wu TT, Lunagomez S, Lynch PM, 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(6):1237–44.
doi: 10.1200/JCO.2005.01.305
Bouzourene H, Bosman FT, Seelentag W, Matter M, Coucke P. Importance of tumor regression assessment in predicting the outcome in patients with locally advanced rectal carcinoma who are treated with preoperative radiotherapy. Cancer. 2002;94(4):1121–30.
doi: 10.1002/cncr.10327
Rodel C, Martus P, Papadoupolos T, Fuzesi L, Klimpfinger M, Fietkau R, et al. Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol. 2005;23(34):8688–96.
doi: 10.1200/JCO.2005.02.1329
Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard V, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol. 2007;18(2):299–304.
doi: 10.1093/annonc/mdl386
Adam R, Wicherts DA, de Haas RJ, Aloia T, Levi F, Paule B, et al. Complete pathologic response after preoperative chemotherapy for colorectal liver metastases: Myth or reality? J Clin Oncol. 2008;26(10):1635–41.
doi: 10.1200/JCO.2007.13.7471
Blazer DG 3rd, Kishi Y, Maru DM, Kopetz S, Chun YS, Overman MJ, et al. Pathologic response to preoperative chemotherapy: a new outcome end point after resection of hepatic colorectal metastases. J Clin Oncol. 2008;26(33):5344–51.
doi: 10.1200/JCO.2008.17.5299
Chan G, Hassanain M, Chaudhury P, Vrochides D, Neville A, Cesari M, et al. Pathological response grade of colorectal liver metastases treated with neoadjuvant chemotherapy. HPB (Oxford). 2010;12(4):277–84.
doi: 10.1111/j.1477-2574.2010.00170.x
Chun YS, Vauthey JN, Boonsirikamchai P, Maru DM, Kopetz S, Palavecino M, et al. Association of computed tomography morphologic criteria with pathologic response and survival in patients treated with bevacizumab for colorectal liver metastases. JAMA. 2009;302(21):2338–44.
doi: 10.1001/jama.2009.1755
Kuerer HM, Newman LA, Smith TL, Ames FC, Hunt KK, Dhingra K, et al. Clinical course of breast cancer patients with complete pathologic primary tumor and axillary lymph node response to doxorubicin-based neoadjuvant chemotherapy. J Clin Oncol. 1999;17(2):460–9.
doi: 10.1200/JCO.1999.17.2.460
Higashiyama M, Okami J, Maeda J, Tokunaga T, Fujiwara A, Kodama K, et al. Differences in chemosensitivity between primary and paired metastatic lung cancer tissues: In vitro analysis based on the collagen gel droplet embedded culture drug test (cd-dst). J Thorac Dis. 2012;4(1):40–7.
pubmed: 22295166 pmcid: 3256540
Fleming CA, McCarthy K, Ryan C, McCarthy A, O’Reilly S, O’Mahony D, et al. Evaluation of discordance in primary tumor and lymph node response after neoadjuvant therapy in breast cancer. Clin Breast Cancer. 2018;18(2):e255–61.
doi: 10.1016/j.clbc.2017.11.016
Merlino DJ, Johnson JM, Tuluc M, Gargano S, Stapp R, Harshyne L Jr, et al. Discordant responses between primary head and neck tumors and nodal metastases treated with neoadjuvant nivolumab: correlation of radiographic and pathologic treatment effect. Front Oncol. 2020;10:566315.
doi: 10.3389/fonc.2020.566315
Liu X, Sun W, Wu J, Feng Y, Mao L, Chen M, et al. Major pathologic response assessment and clinical significance of metastatic lymph nodes after neoadjuvant therapy for non-small cell lung cancer. Mod Pathol. 2021;34(11):1990–2199.
doi: 10.1038/s41379-021-00871-1

Auteurs

Meredith C Mason (MC)

Department of Surgery, Division of Surgical Oncology, Emory University School of Medicine, Atlanta, GA, USA.

Maciej Krasnodebski (M)

Department of General, Transplant and Liver Surgery, Medical University of Warsaw, Warsaw, Poland.

Caitlin A Hester (CA)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Anai N Kothari (AN)

Department of Surgery, Division of Surgical Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.

Caeli Barker (C)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yujiro Nishioka (Y)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yi-Ju Chiang (YJ)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Timothy E Newhook (TE)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Ching-Wei D Tzeng (CD)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Yun Shin Chun (YS)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Jean-Nicolas Vauthey (JN)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Hop S Tran Cao (HS)

Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. hstran@mdanderson.org.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH