Pathological treatment response has different prognostic implications for pancreatic cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy

Maeda, Shin; Mederos, Michael A.; Chawla, Akhil; Moore, Alexandra; Shoucair, Sami; Yin, Lingdi; Burkhart, Richard A.; Cameron, John L.; Park, Joon Y.; Girgis, Mark D.; Wainberg, Zev A.; Hines, Oscar J.; Castillo, Carlos Fernández‐del; Qadan, Motaz; Lillemoe, Keith D.; Ferrone, Cristina R.; He, Jin; Wolfgang, Christopher L.; Burns, William R.; Yu, Jun; Donahue, Timothy R.

doi:10.1016/j.surg.2021.10.015

Cited by 11 publications

(18 citation statements)

References 29 publications

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“…223 While the CAP system has been criticized for the lack of difference in survival between score 2 and 3 patients, Maeda et al. 6 reported that scores 2 and 3 have different prognostic meanings for patients treated with neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy. Despite scores 2 and 3 not having a significantly different OS for neoadjuvant chemoradiotherapy, a CAP score of 2 was found to be in an independent prognostic factor for improved OS and DFS for neoadjuvant chemotherapy.…”

Section: Assessment Of Pdac Response To Nat and Prognostic Meaningmentioning

confidence: 99%

“…Despite scores 2 and 3 not having a significantly different OS for neoadjuvant chemoradiotherapy, a CAP score of 2 was found to be in an independent prognostic factor for improved OS and DFS for neoadjuvant chemotherapy. 6 …”

Section: Assessment Of Pdac Response To Nat and Prognostic Meaningmentioning

confidence: 99%

“… 3 , 4 , 5 Surgical resection is the only cure for PDAC currently, but patients often present with metastatic disease or unresectable primary tumors at diagnosis. 6 Furthermore, surgical resection alone is insufficient: up to 80% of patients with localized tumors who undergo surgical resection with curative intent experience recurrence. 6 …”

Section: Introductionmentioning

confidence: 99%

“… 6 Furthermore, surgical resection alone is insufficient: up to 80% of patients with localized tumors who undergo surgical resection with curative intent experience recurrence. 6 …”

Section: Introductionmentioning

confidence: 99%

“…However, there has been a recent shift of focus toward a neoadjuvant approach against PDAC. Hypothesized benefits of neoadjuvant therapy (NAT) include early treatment of micrometastases, guaranteed delivery of systemic therapy, downstaging, improved rates of negative lymph nodes, enhanced ability to select patients suitable for surgery, and increased rates of margin negative (R0) resections 6,13,14 . NAT is currently recommended by the National Comprehensive Cancer Network (NCCN) for patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) 15,16 …”

Section: Introductionmentioning

confidence: 99%

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Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study

Kung

2023

MedComm

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Pancreatic ductal adenocarcinoma (PDAC) is an aggressive and lethal malignancy with a high rate of recurrence and a dismal 5‐year survival rate. Contributing to the poor prognosis of PDAC is the lack of early detection, a complex network of signaling pathways and molecular mechanisms, a dense and desmoplastic stroma, and an immunosuppressive tumor microenvironment. A recent shift toward a neoadjuvant approach to treating PDAC has been sparked by the numerous benefits neoadjuvant therapy (NAT) has to offer compared with upfront surgery. However, certain aspects of NAT against PDAC, including the optimal regimen, the use of radiotherapy, and the selection of patients that would benefit from NAT, have yet to be fully elucidated. This review describes the major signaling pathways and molecular mechanisms involved in PDAC initiation and progression in addition to the immunosuppressive tumor microenvironment of PDAC. We then review current guidelines, ongoing research, and future research directions on the use of NAT based on randomized clinical trials and other studies. Finally, the current use of and research regarding targeted therapy for PDAC are examined. This review bridges the molecular understanding of PDAC with its clinical significance, development of novel therapies, and shifting directions in treatment paradigm.

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Section: Assessment Of Pdac Response To Nat and Prognostic Meaningmentioning

confidence: 99%

Section: Assessment Of Pdac Response To Nat and Prognostic Meaningmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“… 6 Furthermore, surgical resection alone is insufficient: up to 80% of patients with localized tumors who undergo surgical resection with curative intent experience recurrence. 6 …”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study

Kung

2023

MedComm

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Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Stoop,

Oba,

et al. 2024

JAMA Netw Open

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ImportancePreoperative chemo(radio)therapy is increasingly used in patients with localized pancreatic adenocarcinoma, leading to pathological complete response (pCR) in a small subset of patients. However, multicenter studies with in-depth data about pCR are lacking.ObjectiveTo investigate the incidence, outcome, and risk factors of pCR after preoperative chemo(radio)therapy.Design, Setting, and ParticipantsThis observational, international, multicenter cohort study assessed all consecutive patients with pathology-proven localized pancreatic adenocarcinoma who underwent resection after 2 or more cycles of chemotherapy (with or without radiotherapy) in 19 centers from 8 countries (January 1, 2010, to December 31, 2018). Data collection was performed from February 1, 2020, to April 30, 2022, and analyses from January 1, 2022, to December 31, 2023. Median follow-up was 19 months.ExposuresPreoperative chemotherapy (with or without radiotherapy) followed by resection.Main Outcomes and MeasuresThe incidence of pCR (defined as absence of vital tumor cells in the sampled pancreas specimen after resection), its association with OS from surgery, and factors associated with pCR. Factors associated with overall survival (OS) and pCR were investigated with Cox proportional hazards and logistic regression models, respectively.ResultsOverall, 1758 patients (mean [SD] age, 64 [9] years; 879 [50.0%] male) were studied. The rate of pCR was 4.8% (n = 85), and pCR was associated with OS (hazard ratio, 0.46; 95% CI, 0.26-0.83). The 1-, 3-, and 5-year OS rates were 95%, 82%, and 63% in patients with pCR vs 80%, 46%, and 30% in patients without pCR, respectively (P &lt; .001). Factors associated with pCR included preoperative multiagent chemotherapy other than (m)FOLFIRINOX ([modified] leucovorin calcium [folinic acid], fluorouracil, irinotecan hydrochloride, and oxaliplatin) (odds ratio [OR], 0.48; 95% CI, 0.26-0.87), preoperative conventional radiotherapy (OR, 2.03; 95% CI, 1.00-4.10), preoperative stereotactic body radiotherapy (OR, 8.91; 95% CI, 4.17-19.05), radiologic response (OR, 13.00; 95% CI, 7.02-24.08), and normal(ized) serum carbohydrate antigen 19-9 after preoperative therapy (OR, 3.76; 95% CI, 1.79-7.89).Conclusions and RelevanceThis international, retrospective cohort study found that pCR occurred in 4.8% of patients with resected localized pancreatic adenocarcinoma after preoperative chemo(radio)therapy. Although pCR does not reflect cure, it is associated with improved OS, with a doubled 5-year OS of 63% compared with 30% in patients without pCR. Factors associated with pCR related to preoperative chemo(radio)therapy regimens and anatomical and biological disease response features may have implications for treatment strategies that require validation in prospective studies because they may not universally apply to all patients with pancreatic adenocarcinoma.

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Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer

Ghabi

Shoucair²,

Ding³

et al. 2023

Journal of Gastrointestinal Surgery

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Pathological treatment response has different prognostic implications for pancreatic cancer patients treated with neoadjuvant chemotherapy or chemoradiotherapy

Cited by 11 publications

References 29 publications

Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study

Targeted therapy for pancreatic ductal adenocarcinoma: Mechanisms and clinical study

Pathological Complete Response in Patients With Resected Pancreatic Adenocarcinoma After Preoperative Chemotherapy

Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer

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