Adjuvant Chemotherapy After Neoadjuvant Chemotherapy for Pancreatic Cancer is Associated with Improved Survival for Patients with Low-Risk Pathology

Olecki, Elizabeth J.; Stahl, Kelly A.; Torres, Madeline B.; Peng, June S.; Dixon, Matthew; Shen, Chan; Gusani, Niraj J.

doi:10.1245/s10434-020-09546-8

Cited by 10 publications

(12 citation statements)

References 26 publications

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“…There are no high-level data supporting the use of adjuvant chemotherapy among patients who underwent pancreatectomy after neoadjuvant chemotherapy. Several retrospective analyses have yielded conflicting results, particularly in the subgroup that benefited from adjuvant chemotherapy [17,18,[22][23][24][25]. Some studies have suggested that postoperative chemotherapy was significantly associated with improved survival for patients with a lower lymph node burden [22,23], whereas one study reported a survival benefit for patients with lymph node positive disease [24].…”

Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

“…Several retrospective analyses have yielded conflicting results, particularly in the subgroup that benefited from adjuvant chemotherapy [17,18,[22][23][24][25]. Some studies have suggested that postoperative chemotherapy was significantly associated with improved survival for patients with a lower lymph node burden [22,23], whereas one study reported a survival benefit for patients with lymph node positive disease [24]. These early studies, however, included various drugs as neoadjuvant chemotherapy, and a large proportion of patients received only chemoradiation as preoperative treatment [22][23][24].…”

Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

“…Some studies have suggested that postoperative chemotherapy was significantly associated with improved survival for patients with a lower lymph node burden [22,23], whereas one study reported a survival benefit for patients with lymph node positive disease [24]. These early studies, however, included various drugs as neoadjuvant chemotherapy, and a large proportion of patients received only chemoradiation as preoperative treatment [22][23][24]. A retrospective cohort study using the US National Cancer database showed that adjuvant chemotherapy was associated with a longer survival only in patients with a lymph node ratio (LNR) between 0.01 and 0.149, not in nodenegative patients or those with a LNR greater than 0.15 [25], and a recent nationwide retrospective study by Kamarajah et al [17] found that adjuvant chemotherapy was associated with a survival benefit in patients with ypN0 and ypN1, but not ypN2.…”

Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

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Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX

Lee¹,

Hwang²,

Yoo³

et al. 2023

Cancer Res Treat

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The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear.This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population. Materials and MethodsThis retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status. ResultsAdjuvant chemotherapy was administered to 149 (68.3%) patients. In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median 13.8 months [95% CI, 11.0-19.1] vs. 8.2 months [95% CI, 6.5-12.0], p<0.001; and OS: median 38.0 months [95% CI, 32.2-not assessable] vs. 25.7 months [95% CI, 18.3-not assessable], p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p<0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs observation; DFS, hazard ratio[HR] 0.51 (95% CI, 0.36-0.71, p<0.001); OS, HR 0.45 (95% CI, 0.29-0.71, p<0.001).

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Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

Section: A C C E P T E D a R T I C L E Korean Cancer Associationmentioning

confidence: 99%

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Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX

Lee¹,

Hwang²,

Yoo³

et al. 2023

Cancer Res Treat

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“…Similarly, in a retrospective NCDB study that included patients with borderline resectable or locally advanced disease who were treated with neoadjuvant therapy, the addition of adjuvant therapy was associated with a survival benefit only among patients with positive margins after resection [ 25 ]. Among patients with stage I-II disease, another NCDB study found that adjuvant therapy after neoadjuvant therapy was associated with higher overall survival only among patients with low-risk pathologic features (i.e., low lymph node ratio, low-grade histology, and negative margin status) [ 26 ]. Taken together, these studies highlight the potential benefit of adjuvant therapy.…”

Section: Adjuvant Chemotherapymentioning

confidence: 99%

Advances and Remaining Challenges in the Treatment for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Sulciner

Ashley

Molina

2022

JCM

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Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest malignancies in the United States. Improvements in imaging have permitted the categorization of patients according to radiologic involvement of surrounding vasculature, i.e., upfront resectable, borderline resectable, and locally advanced disease, and this, in turn, has influenced the sequence of chemotherapy, surgery, and radiation therapy. Though surgical resection remains the only curative treatment option, recent studies have shown improved overall survival with neoadjuvant chemotherapy, especially among patients with borderline resectable/locally advanced disease. The role of radiologic imaging after neoadjuvant therapy and the potential benefit of adjuvant therapy for borderline resectable and locally advanced disease remain areas of ongoing investigation. The advances made in the treatment of patients with borderline resectable/locally advanced disease are promising, yet disparities in access to cancer care persist. This review highlights the significant advances that have been made in the treatment of borderline resectable and locally advanced PDAC, while also calling attention to the remaining challenges.

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“…In the setting of N0 disease after NAT, the incremental benefit derived from AT remains to be evaluated. Furthermore, the effects of other high-risk pathologic features such as margin status, tumor grade, lymphovascular invasion (LVI), and perineural invasion (PNI) have not yet been evaluated in N0 specimens after NAT . Conceptually, the detection of tumor-specific features, or the lack thereof, in patients with N0 disease after NAT may allow investigators to identify a cohort of patients for whom AT may be indicated or omitted.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy

et al. 2023

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ImportanceNeoadjuvant therapy (NAT) is rarely associated with a complete histopathologic response in patients with pancreatic ductal adenocarcinoma (PDAC) but results in downstaging of regional nodal disease. Such nodal downstaging after NAT may have implications for the use of additional adjuvant therapy (AT).ObjectivesTo examine the prognostic implications of AT in patients with node-negative (N0) disease after NAT and to identify factors associated with progression-free (PFS) and overall survival (OS).Design, Setting, and ParticipantsA retrospective review was conducted using data from 2 high-volume, tertiary care academic centers (University of Pittsburgh Medical Center and the Medical College of Wisconsin). Prospectively maintained pancreatic cancer databases at both institutes were searched to identify patients with localized PDAC treated with preoperative therapy and subsequent surgical resection between 2010 and 2019, with N0 disease on final histopathology.ExposuresPatients received NAT consisting of chemotherapy with or without concomitant neoadjuvant radiation (NART). For patients who received NART, chemotherapy regimens were gemcitabine or 5-fluoururacil based and included stereotactic body radiotherapy (SBRT) or intensity-modulated radiation therapy (IMRT) after all intended chemotherapy and approximately 4 to 5 weeks before anticipated surgery. Adjuvant therapy consisted of gemcitabine-based therapy or FOLFIRINOX; when used, adjuvant radiation was commonly administered as either SBRT or IMRT.Main Outcomes and MeasuresThe association of AT with PFS and OS was evaluated in the overall cohort and in different subgroups. The interaction between AT and other clinicopathologic variables was examined on Cox proportional hazards regression analysis.ResultsIn this cohort study, 430 consecutive patients were treated between 2010 and 2019. Patients had a mean (SD) age of 65.2 (9.4) years, and 220 (51.2%) were women. The predominant NAT was gemcitabine based (196 patients [45.6%]), with a median duration of 2.7 cycles (IQR, 1.5-3.4). Neoadjuvant radiation was administered to 279 patients (64.9%). Pancreatoduodenectomy was performed in 310 patients (72.1%), and 160 (37.2%) required concomitant vascular resection. The median lymph node yield was 26 (IQR, 19-34); perineural invasion (PNI), lymphovascular invasion (LVI), and residual positive margins (R1) were found in 254 (59.3%), 92 (22.0%), and 87 (21.1%) patients, respectively. The restricted mean OS was 5.2 years (95% CI, 4.8-5.7). On adjusted analysis, PNI, LVI, and poorly differentiated tumors were independently associated with worse PFS and OS in N0 disease after NAT, with hazard ratios (95% CIs) of 2.04 (1.43-2.92; P &lt; .001) and 1.68 (1.14-2.48; P = .009), 1.47 (1.08-1.98; P = .01) and 1.54 (1.10-2.14; P = .01), and 1.90 (1.18-3.07; P = .008) and 1.98 (1.20-3.26; P = .008), respectively. Although AT was associated with prolonged survival in the overall cohort, the effect was reduced in patients who received NART and strengthened in patients with PNI (AT × PNI interaction: hazard ratio, 0.55 [95% CI, 0.32-0.97]; P = .04).Conclusions and RelevanceThe findings of this cohort study suggest a survival benefit for AT in patients with N0 disease after NAT and surgical resection. This survival benefit may be most pronounced in patients with PNI.

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Adjuvant Chemotherapy After Neoadjuvant Chemotherapy for Pancreatic Cancer is Associated with Improved Survival for Patients with Low-Risk Pathology

Cited by 10 publications

References 26 publications

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX

Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX

Advances and Remaining Challenges in the Treatment for Borderline Resectable and Locally Advanced Pancreatic Ductal Adenocarcinoma

Evaluation of Adjuvant Chemotherapy Survival Outcomes Among Patients With Surgically Resected Pancreatic Carcinoma With Node-Negative Disease After Neoadjuvant Therapy

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