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05.01.2022 | Gastrointestinal Oncology

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels

verfasst von: Ankit Dhiman, MBBS, MS, Charles C. Vining, MD, Hunter D. D. Witmer, MD, Divya Sood, MD, Ardaman Shergill, MD, Hedy Kindler, MD, Kevin K. Roggin, MD, Mitchell C. Posner, MD, Osmanuddin S. Ahmed, MD, Stanley Liauw, MD, Sean Pitroda, MD, Chih-Yi Liao, MD, Theodore Karrison, PhD, Ralph Weichselbaum, MD, Blase Polite, MD, Oliver S. Eng, MD, Daniel V. T. Catenacci, MD, Kiran K. Turaga, MD, MPH

Erschienen in: Annals of Surgical Oncology | Ausgabe 7/2022

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Abstract

Background

Metastatic adenocarcinomas of foregut origin are aggressive and have limited treatment options, poor quality of life, and a dismal prognosis. A subset of such patients with limited metastatic disease might have favorable outcomes with locoregional metastasis-directed therapies. This study investigates the role of sequential cytoreductive interventions in addition to the standard of care chemotherapy in patients with oligometastatic foregut adenocarcinoma.

Methods

This is a single-center, phase II, open-label randomized clinical trial. Eligible patients include adults with synchronous or metachronous oligometastatic (metastasis limited to two sites and amenable for curative/ablative treatment) adenocarcinoma of the foregut without progression after induction chemotherapy and having undetectable ctDNA. These patients will undergo induction chemotherapy and will then be randomized (1:1) to either sequential curative intervention followed by maintenance chemotherapy versus routine continued chemotherapy. The primary endpoint is progression-free survival (PFS), and a total of 48 patients will be enrolled to detect an improvement in the median PFS in the intervention arm with a hazard ratio (HR) of 0.5 with 80% power and a one-sided alpha of 0.1. Secondary endpoints include disease-free survival (DFS) in the intervention arm, overall survival (OS), ctDNA conversion rate pre/post-induction chemotherapy, ctDNA PFS, PFS₂, adverse events, quality of life, and financial toxicity.

Discussion

This is the first randomized study that aims to prospectively evaluate the efficacy and safety of surgical/ablative interventions in patients with ctDNA-negative oligometastatic adenocarcinoma of foregut origin post-induction chemotherapy. The results from this study will likely develop pertinent, timely, and relevant knowledge in oncology.

Nur mit Berechtigung zugänglich

Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.CrossRefPubMed

Ajani JA, D’Amico TA, Almhanna K, et al. Gastric cancer, version 3.2016, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2016;14(10):1286–312. https://doi.org/10.6004/jnccn.2016.0137.CrossRefPubMed

Ajani JA, D’Amico TA, Bentrem DJ, et al. Esophageal and esophagogastric junction cancers, version 2.2019, NCCN clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2019;17(7):855–83. https://doi.org/10.6004/jnccn.2019.0033.CrossRefPubMed

Tempero MA, Malafa MP, Chiorean EG, et al. Pancreatic adenocarcinoma, version 1.2019. J Natl Compr Canc Netw. 2019;17(3):202–10. https://doi.org/10.6004/jnccn.2019.0014.CrossRefPubMed

Al-Batran SE, Hofheinz RD, Reichart A, et al. Quality of life and outcome of patients with metastatic pancreatic cancer receiving first-line chemotherapy with nab-paclitaxel and gemcitabine: real-life results from the prospective QOLIXANE trial of the platform for outcome, quality of life and translational research on pancreatic cancer registry. Int J Cancer. 2021;148(6):1478–88. https://doi.org/10.1002/ijc.33336.CrossRefPubMed

Frigerio I, Regi P, Giardino A, et al. Downstaging in stage IV pancreatic cancer: a new population eligible for surgery? Ann Surg Oncol. 2017;24(8):2397–403. https://doi.org/10.1245/s10434-017-5885-4.CrossRefPubMed

Han DS, Suh YS, Kong SH, et al. Outcomes of surgery aiming at curative resection in good responder to induction chemotherapy for gastric cancer with distant metastases. J Surg Oncol. 2013;107(5):511–6. https://doi.org/10.1002/jso.23284.CrossRefPubMed

Kandel P, Wallace MB, Stauffer J, et al. Survival of patients with oligometastatic pancreatic ductal adenocarcinoma treated with combined modality treatment including surgical resection: a pilot study. J Pancreat Cancer. 2018;4(1):88–94. https://doi.org/10.1089/pancan.2018.0011.CrossRefPubMedPubMedCentral

Schmidt T, Alldinger I, Blank S, et al. Surgery in oesophago-gastric cancer with metastatic disease: treatment, prognosis and preoperative patient selection. Eur J Surg Oncol. 2015;41(10):1340–7. https://doi.org/10.1016/j.ejso.2015.05.005.CrossRefPubMed

10.

Shrikhande SV, Kleeff J, Reiser C, et al. Pancreatic resection for M1 pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2007;14(1):118–27. https://doi.org/10.1245/s10434-006-9131-8.CrossRefPubMed

11.

Tachezy M, Gebauer F, Janot M, et al. Synchronous resections of hepatic oligometastatic pancreatic cancer: disputing a principle in a time of safe pancreatic operations in a retrospective multicenter analysis. Surgery. 2016;160(1):136–44. https://doi.org/10.1016/j.surg.2016.02.019.CrossRefPubMed

12.

Wright GP, Poruk KE, Zenati MS, et al. Primary tumor resection following favorable response to systemic chemotherapy in stage IV pancreatic adenocarcinoma with synchronous metastases: a bi-institutional analysis. J Gastrointest Surg. 2016;20(11):1830–5. https://doi.org/10.1007/s11605-016-3256-2.CrossRefPubMed

13.

Al-Batran SE, Homann N, Pauligk C, et al. Effect of neoadjuvant chemotherapy followed by surgical resection on survival in patients with limited metastatic gastric or gastroesophageal junction cancer: the AIO-FLOT3 trial. JAMA Oncol. 2017;3(9):1237–44. https://doi.org/10.1001/jamaoncol.2017.0515.CrossRefPubMedPubMedCentral

14.

Hellman S, Weichselbaum RR. Oligometastases. J Clin Oncol. 1995;13(1):8–10. https://doi.org/10.1200/jco.1995.13.1.8.CrossRefPubMed

15.

Weichselbaum RR, Hellman S. Oligometastases revisited. Nat Rev Clin Oncol. 2011;8(6):378–82. https://doi.org/10.1038/nrclinonc.2011.44.CrossRefPubMed

16.

Franzese C, Bonu ML, Comito T, et al. Stereotactic body radiotherapy in the management of oligometastatic and recurrent biliary tract cancer: single-institution analysis of outcome and toxicity. J Cancer Res Clin Oncol. 2020;146(9):2289–97. https://doi.org/10.1007/s00432-020-03285-9.CrossRefPubMed

17.

Gomez DR, Blumenschein GR Jr, Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol. 2016;17(12):1672–82. https://doi.org/10.1016/s1470-2045(16)30532-0.CrossRefPubMedPubMedCentral

18.

Ruers T, Punt C, Van Coevorden F, et al. Radiofrequency ablation combined with systemic treatment versus systemic treatment alone in patients with non-resectable colorectal liver metastases: a randomized EORTC Intergroup phase II study (EORTC 40004). Ann Oncol. 2012;23(10):2619–26. https://doi.org/10.1093/annonc/mds053.CrossRefPubMedPubMedCentral

19.

Ruers T, Van Coevorden F, Punt CJ, et al. Local treatment of unresectable colorectal liver metastases: results of a randomized phase II trial. J Natl Cancer Inst. 2017. https://doi.org/10.1093/jnci/djx015.CrossRefPubMedPubMedCentral

20.

Ost P, Reynders D, Decaestecker K, et al. Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence: a prospective, randomized, multicenter phase II trial. J Clin Oncol. 2018;36(5):446–53. https://doi.org/10.1200/jco.2017.75.4853.CrossRefPubMed

21.

Ma M, Zhu H, Zhang C, Sun X, Gao X, Chen G. “Liquid biopsy”-ctDNA detection with great potential and challenges. Ann Transl Med. 2015;3(16):235. https://doi.org/10.3978/j.issn.2305-5839.2015.09.29.CrossRefPubMedPubMedCentral

22.

Spindler KL, Appelt AL, Pallisgaard N, Andersen RF, Brandslund I, Jakobsen A. Cell-free DNA in healthy individuals, noncancerous disease and strong prognostic value in colorectal cancer. Int J Cancer. 2014;135(12):2984–91. https://doi.org/10.1002/ijc.28946.CrossRefPubMed

23.

Maron SB, Chase LM, Lomnicki S, et al. Circulating tumor DNA sequencing analysis of gastroesophageal adenocarcinoma. Clin Cancer Res. 2019;25(23):7098–112. https://doi.org/10.1158/1078-0432.Ccr-19-1704.CrossRefPubMedPubMedCentral

24.

Pietrasz D, Pécuchet N, Garlan F, et al. Plasma circulating tumor DNA in pancreatic cancer patients is a prognostic marker. Clin Cancer Res. 2017;23(1):116–23. https://doi.org/10.1158/1078-0432.Ccr-16-0806.CrossRefPubMed

25.

Parikh AR, Van Seventer EE, Siravegna G, et al. Minimal residual disease detection using a plasma-only circulating tumor DNA assay in colorectal cancer patients. Clin Cancer Res. 2021. https://doi.org/10.1158/1078-0432.ccr-21-0410.CrossRefPubMedPubMedCentral

26.

Odegaard JI, Vincent JJ, Mortimer S, et al. Validation of a plasma-based comprehensive cancer genotyping assay utilizing orthogonal tissue- and plasma-based methodologies. Clin Cancer Res. 2018;24(15):3539–49. https://doi.org/10.1158/1078-0432.Ccr-17-3831.CrossRefPubMed

27.

Bettegowda C, Sausen M, Leary RJ, et al. Detection of circulating tumor DNA in early- and late-stage human malignancies. Sci Transl Med. 2014;6(224):224ra24. https://doi.org/10.1126/scitranslmed.3007094.CrossRefPubMedPubMedCentral

28.

Gao Y, Xi H, Wei B, et al. Association between liquid biopsy and prognosis of gastric cancer patients: a systematic review and meta-analysis. Front Oncol. 2019;9:1222. https://doi.org/10.3389/fonc.2019.01222.CrossRefPubMedPubMedCentral

29.

Tie J, Cohen JD, Wang Y, et al. Circulating tumor DNA analyses as markers of recurrence risk and benefit of adjuvant therapy for stage III colon cancer. JAMA Oncol. 2019;5(12):1710–7. https://doi.org/10.1001/jamaoncol.2019.3616.CrossRefPubMedPubMedCentral

30.

Rumiato E, Boldrin E, Malacrida S, et al. Detection of genetic alterations in cfDNA as a possible strategy to monitor the neoplastic progression of Barrett’s esophagus. Transl Res. 2017;190:16-24.e1. https://doi.org/10.1016/j.trsl.2017.09.004.CrossRefPubMed

31.

Hu ZY, Xie N, Tian C, et al. Identifying circulating tumor DNA mutation profiles in metastatic breast cancer patients with multiline resistance. EBioMedicine. 2018;32:111–8. https://doi.org/10.1016/j.ebiom.2018.05.015.CrossRefPubMedPubMedCentral

32.

Tie J, Wang Y, Tomasetti C, et al. Circulating tumor DNA analysis detects minimal residual disease and predicts recurrence in patients with stage II colon cancer. Sci Transl Med. 2016;8(346):346ra92. https://doi.org/10.1126/scitranslmed.aaf6219.CrossRefPubMedPubMedCentral

33.

Garcia-Murillas I, Schiavon G, Weigelt B, et al. Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer. Sci Transl Med. 2015;7(302):302ra133. https://doi.org/10.1126/scitranslmed.aab0021.CrossRefPubMed

34.

Chaudhuri AA, Chabon JJ, Lovejoy AF, et al. Early detection of molecular residual disease in localized lung cancer by circulating tumor DNA profiling. Cancer Discov. 2017;7(12):1394–403. https://doi.org/10.1158/2159-8290.Cd-17-0716.CrossRefPubMedPubMedCentral

35.

Chan AW, Tetzlaff JM, Altman DG, et al. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013;158(3):200–7. https://doi.org/10.7326/0003-4819-158-3-201302050-00583.CrossRefPubMedPubMedCentral

36.

Aaronson NK, Ahmedzai S, Bergman B, et al. The European organization for research and treatment of cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993;85(5):365–76. https://doi.org/10.1093/jnci/85.5.365.CrossRefPubMed

37.

de Souza JA, Yap BJ, Hlubocky FJ, et al. The development of a financial toxicity patient-reported outcome in cancer: The COST measure. Cancer. 2014;120(20):3245–53. https://doi.org/10.1002/cncr.28814.CrossRefPubMed

38.

Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53(282):457. https://doi.org/10.2307/2281868.CrossRef

39.

Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics. 1982;38(1):29. https://doi.org/10.2307/2530286.CrossRef

40.

Wieand S, Schroeder G, O’Fallon JR. Stopping when the experimental regimen does not appear to help. Stat Med. 1994;13(13–14):1453–8. https://doi.org/10.1002/sim.4780131321.CrossRefPubMed

41.

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7–33. https://doi.org/10.3322/caac.21654.CrossRefPubMed

42.

Pitroda SP, Weichselbaum RR. Integrated molecular and clinical staging defines the spectrum of metastatic cancer. Nat Rev Clin Oncol. 2019;16(9):581–8. https://doi.org/10.1038/s41571-019-0220-6.CrossRefPubMed

43.

Kemeny NE, Chou JF, Boucher TM, et al. Updated long-term survival for patients with metastatic colorectal cancer treated with liver resection followed by hepatic arterial infusion and systemic chemotherapy. J Surg Oncol. 2016;113(5):477–84. https://doi.org/10.1002/jso.24189.CrossRefPubMedPubMedCentral

44.

Okumura T, Boku N, Hishida T, et al. Surgical outcome and prognostic stratification for pulmonary metastasis from colorectal cancer. Ann Thorac Surg. 2017;104(3):979–87. https://doi.org/10.1016/j.athoracsur.2017.03.021.CrossRefPubMed

45.

Palma DA, Olson R, Harrow S, et al. Stereotactic ablative radiotherapy versus standard of care palliative treatment in patients with oligometastatic cancers (SABR-COMET): a randomised, phase 2, open-label trial. Lancet. 2019;393(10185):2051–8. https://doi.org/10.1016/s0140-6736(18)32487-5.CrossRefPubMed

46.

Fujitani K, Yang HK, Mizusawa J, et al. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016;17(3):309–18. https://doi.org/10.1016/s1470-2045(15)00553-7.CrossRefPubMed

47.

Leal A, Van Grieken NCT, Palsgrove DN, et al. White blood cell and cell-free DNA analyses for detection of residual disease in gastric cancer. Nat Commun. 2020. https://doi.org/10.1038/s41467-020-14310-3.CrossRefPubMedPubMedCentral

48.

Spindler KL, Pallisgaard N, Vogelius I, Jakobsen A. Quantitative cell-free DNA, KRAS, and BRAF mutations in plasma from patients with metastatic colorectal cancer during treatment with cetuximab and irinotecan. Clin Cancer Res. 2012;18(4):1177–85. https://doi.org/10.1158/1078-0432.Ccr-11-0564.CrossRefPubMed

Titel: Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels
verfasst von: Ankit Dhiman, MBBS, MS
Charles C. Vining, MD
Hunter D. D. Witmer, MD
Divya Sood, MD
Ardaman Shergill, MD
Hedy Kindler, MD
Kevin K. Roggin, MD
Mitchell C. Posner, MD
Osmanuddin S. Ahmed, MD
Stanley Liauw, MD
Sean Pitroda, MD
Chih-Yi Liao, MD
Theodore Karrison, PhD
Ralph Weichselbaum, MD
Blase Polite, MD
Oliver S. Eng, MD
Daniel V. T. Catenacci, MD
Kiran K. Turaga, MD, MPH
Publikationsdatum: 05.01.2022
Verlag: Springer International Publishing
Erschienen in: Annals of Surgical Oncology / Ausgabe 7/2022
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-021-11249-7

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Springer Medizin

Phase II Prospective, Open-Label Randomized Controlled Trial Comparing Standard of Care Chemotherapy With and Without Sequential Cytoreductive Interventions for Patients with Oligometastatic Foregut Adenocarcinoma and Undetectable Circulating Tumor Deoxyribose Nucleic Acid (ctDNA) Levels