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Unrecognized development of chemoresistance and/or distant metastases during induction chemotherapy for pancreatic adenocarcinoma
Background
Induction Chemotherapy (IC) is often used in the treatment of pancreatic cancer (PC) and concurrent chemoradiotherapy (CRT), when given, usually follows the complete delivery of IC. We aim in this study to determine the incidence of CA19-9 rise during IC that is not associated with radiological/US progression, when patients are referred for CRT. Such progression may indicate the development of occult distant metastases and/or chemoresistance.
Methods
We retrospectively reviewed all charts of patients diagnosed with PC and referred for CRT following IC during the period of 2015-2021. Patients were eligible for this study if they met all of the following criteria: received IC, Staging/restaging imaging studies demonstrated no evidence of distant metastases or progression of locoregional disease at any point prior to CRT referral, availability of serial CA19-9 and bilirubin measurements during the IC phase. CA19-9 progression is defined as an increase in CA19-9 by at least 25% compared to prior measurement in the absence of elevated bilirubin.
Results
Thirty four patients, 21 males and 13 females, met the eligibility criteria with a median age of 69 years. PC was located in the head/neck or body of the pancreas in 21 and 10 cases respectively. The location of the tumor could not be determined in 3 cases. The disease was considered resectable, borderline resectable or unresectable in 5, 23 and 6 cases, respectively. Three patients had tumors with complete radiological clinical response at the time of referral for CRT. Partial response was noticed in 15 cases and stable disease was seen in 16 cases. Chemotherapy regimens included FOLFIRINOX (22 cases), Gemcitabine-Abraxane (10 cases) or Gemcitabine alone (2 cases). CA19-9 was rising by more than 25% ( 26%-337%, median 47%) with total bilirubin levels of less than 1, before referral for CRT in 10/34 cases (29%).
Conclusions
There may be high incidence of unrecognized chemical tumor progression, as measured by a CA19-9 rise, and/or development of chemoresistance during IC and before the delivery of CRT. This phenomenon may explain the lack of impact of CRT when delivered after completion of IC when only radiological studies are used to restage patients prior to initiation of CRT. Our findings need to be confirmed in a larger database and if confirmed would suggest the inclusion of CA19-9 levels in the restaging process and possible demonstration of a better impact of CRT if patients with CA19-9 rise are not included in the analysis to evaluate the potential benefit of CRT.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosures
All authors have declared no conflicts of interest.
