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Factors Predicting Response, Perioperative Outcomes, and Survival Following Total Neoadjuvant Therapy for Borderline/Locally Advanced Pancreatic Cancer.
Truty, Mark J; Kendrick, Michael L; Nagorney, David M; Smoot, Rory L; Cleary, Sean P; Graham, Rondell P; Goenka, Ajit H; Hallemeier, Christopher L; Haddock, Michel G; Harmsen, William S; Mahipal, Amit; McWilliams, Robert R; Halfdanarson, Thorvardur R; Grothey, Axel F.
  • Truty MJ; Division of Hepatobiliary and Pancreas Surgery.
  • Kendrick ML; Division of Hepatobiliary and Pancreas Surgery.
  • Nagorney DM; Division of Hepatobiliary and Pancreas Surgery.
  • Smoot RL; Division of Hepatobiliary and Pancreas Surgery.
  • Cleary SP; Division of Hepatobiliary and Pancreas Surgery.
  • Graham RP; Division of Anatomic Pathology.
  • Goenka AH; Division of Radiology and Nuclear Medicine.
  • Hallemeier CL; Division of Radiation Oncology.
  • Haddock MG; Division of Radiation Oncology.
  • Harmsen WS; Division of Biomedical Statistic and Informatics.
  • Mahipal A; Division of Medical Oncology.
  • McWilliams RR; Division of Medical Oncology.
  • Halfdanarson TR; Division of Medical Oncology.
  • Grothey AF; Division of Medical Oncology.
Ann Surg ; 273(2): 341-349, 2021 02 01.
Article en En | MEDLINE | ID: mdl-30946090
ABSTRACT

OBJECTIVE:

To identify predictive factors associated with operative morbidity, mortality, and survival outcomes in patients with borderline resectable (BR) or locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) undergoing total neoadjuvant therapy (TNT).

BACKGROUND:

The optimal preoperative treatment sequencing for BR/LA PDA is unknown. TNT, or systemic chemotherapy followed by chemoradiation (CRT), addresses both occult metastases and positive margin risks and thus is a potentially optimal strategy; however, factors predictive of perioperative and survival outcomes are currently undefined.

METHODS:

We reviewed our experience in BR/LA patients undergoing resection from 2010 to 2017 following TNT assessing operative morbidity, mortality, and survival in order to define outcome predictors and response endpoints.

RESULTS:

One hundred ninety-four patients underwent resection after TNT, including 123 (63%) BR and 71 (37%) LA PDAC. FOLFIRINOX or gemcitabine along with nab-paclitaxel were used in 165 (85%) and 65 (34%) patients, with 36 (19%) requiring chemotherapeutic switch before long-course CRT and subsequent resection. Radiologic anatomical downstaging was uncommon (28%). En bloc venous and/or arterial resection was required in 125 (65%) patients with 94% of patients achieving R0 margins. The 90-day major morbidity and mortality was 36% and 6.7%, respectively. Excluding operative mortalities, the median, 1-year, 2-year, and 3-year recurrence-free survival (RFS) [overall survival (OS)] rates were 23.5 (58.8) months, 65 (96)%, 48 (78)%, and 32 (62)%, respectively. Radiologic downstaging, vascular resection, and chemotherapy regimen/switch were not associated with survival. Only 3 factors independently associated with prolonged survival, including extended duration (≥6 cycles) chemotherapy, optimal post-chemotherapy CA19-9 response, and major pathologic response. Patients achieving all 3 factors had superior survival outcomes with a survival detriment for each failing factor. In a subset of patients with interval metabolic (PET) imaging after initial chemotherapy, complete metabolic response highly correlated with major pathologic response.

CONCLUSION:

Our TNT experience in resected BR/LA PDAC revealed high negative margin rates despite low radiologic downstaging. Extended duration chemotherapy with associated biochemical and pathologic responses highly predicted postoperative survival. Potential modifications of initial chemotherapy treatment include extending cycle duration to normalize CA19-9 or achieve complete metabolic response, or consideration of chemotherapeutic switch in order to achieve these factors may improve survival before moving forward with CRT and subsequent resection.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pancreatectomía / Neoplasias Pancreáticas / Complicaciones Posoperatorias / Protocolos de Quimioterapia Combinada Antineoplásica / Terapia Neoadyuvante / Carcinoma Ductal Pancreático Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Año: 2021 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Pancreatectomía / Neoplasias Pancreáticas / Complicaciones Posoperatorias / Protocolos de Quimioterapia Combinada Antineoplásica / Terapia Neoadyuvante / Carcinoma Ductal Pancreático Tipo de estudio: Etiology_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Año: 2021 Tipo del documento: Article