Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy

Swords, Douglas S.; Francis, Samual; Lloyd, Shane; Mulvihill, Sean J.; Gruhl, J.D.; Christensen, Miles C.; Stoddard, Gregory J.; Firpo, Matthew A.; Scaife, Courtney L.

doi:10.1007/s11605-018-3953-0

Cited by 12 publications

(24 citation statements)

References 46 publications

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“…Second, the present study adopted PSM to adjust for selection biases for receiving either AC or noAC to create well-balanced cohorts. Finally, previous analyses 13 , 14 did not establish any survival benefit for AC in patients with low-risk disease, which was demonstrated in the present study.…”

Section: Discussioncontrasting

confidence: 63%

“…To date, evidence on whether AC after NAT and surgery confers incremental advantage remains an ongoing debate as several retrospective studies on this matter have yielded conflicting results. 13 – 18 Previous NCDB analyses by Swords et al 13 and de Geus et al 14 have attempted to study the benefit of AC following NAT. Swords et al 13 reported that AC was associated with improved survival only in patients with a lymph node ratio between 0.01 and 0.14, not in patients with node-negative disease or a lymph node ratio > 0.15.…”

Section: Discussionmentioning

confidence: 99%

“… 13 – 18 Previous NCDB analyses by Swords et al 13 and de Geus et al 14 have attempted to study the benefit of AC following NAT. Swords et al 13 reported that AC was associated with improved survival only in patients with a lymph node ratio between 0.01 and 0.14, not in patients with node-negative disease or a lymph node ratio > 0.15. On the other hand, de Geus et al 14 found AC was not associated with improved survival in comparable settings, even in patients with node-positive or margin-positive disease.…”

Section: Discussionmentioning

confidence: 99%

“…Although the benefit of AC to patients who have undergone resection first is clear, the benefit of AC after NAC and resection is less well-established. 13 – 19 First, previous retrospective analyses investigating the added benefit of AC after NAT and resection have yielded conflicting results, as some suggested benefit in certain subgroups only. 13 – 19 Second, while guidelines from the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommend considering additional AC in this setting, those recommendations likely represent an extrapolation from data of adjuvant trials.…”

mentioning

confidence: 99%

“… 13 – 19 First, previous retrospective analyses investigating the added benefit of AC after NAT and resection have yielded conflicting results, as some suggested benefit in certain subgroups only. 13 – 19 Second, while guidelines from the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) recommend considering additional AC in this setting, those recommendations likely represent an extrapolation from data of adjuvant trials. 4 , 5 Therefore, more high-quality data are needed to truly understand the impact of AC following NAT in patients undergoing resection for PDAC.…”

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confidence: 99%

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Adjuvant Chemotherapy Associated with Survival Benefit Following Neoadjuvant Chemotherapy and Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Population-Based Cohort Study

et al. 2021

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Background Data supporting the routine use of adjuvant chemotherapy (AC) compared with no AC (noAC) following neoadjuvant chemotherapy (NAC) and resection for pancreatic ductal adenocarcinoma (PDAC) are lacking. This study aimed to determine whether AC improves long-term survival in patients receiving NAC and resection. Methods Patients receiving resection for PDAC following NAC from 2004 to 2016 were identified from the National Cancer Data Base (NCDB). Patients with a survival rate of < 6 months were excluded to account for immortal time bias. Propensity score matching (PSM) and Cox regression analysis were performed to account for selection bias and analyze the impact of AC on overall survival. Results Of 4449 (68%) noAC patients and 2111 (32%) AC patients, 2016 noAC patients and 2016 AC patients remained after PSM. After matching, AC was associated with improved survival (median 29.4 vs. 24.9 months; p < 0.001), which remained after multivariable adjustment (HR 0.81, 95% confidence interval [CI] 0.75–0.88; p < 0.001). On multivariable interaction analyses, this benefit persisted irrespective of nodal status: N0 (hazard ratio [HR] 0.80, 95% CI 0.72–0.90; p < 0.001), N1 (HR 0.76, 95% CI 0.67–0.86; p < 0.001), R0 margin status (HR 0.82, 95% CI 0.75–0.89; p < 0.001), R1 margin status (HR 0.77, 95% CI 0.64–0.93; p = 0.007), no neoadjuvant radiotherapy (NART; HR 0.84, 95% CI 0.74–0.96; p = 0.009), and use of NART (HR 0.80, 95% CI 0.73–0.88; p < 0.001). Stratified analysis by nodal, margin, and NART status demonstrated consistent results. Conclusion AC following NAC and resection is associated with improved survival, even in margin-negative and node-negative disease. These findings suggest completing planned systemic treatment should be considered in all resected PDACs previously treated with NAC.

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Section: Discussioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Adjuvant Chemotherapy Associated with Survival Benefit Following Neoadjuvant Chemotherapy and Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Population-Based Cohort Study

et al. 2021

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The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy

Carpenter,

Van Decar,

McCarthy

et al. 2024

Journal of Surgical Oncology

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BackgroundThe benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection.MethodsThe 2019 National Cancer Database was queried for patients with non‐metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down‐staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan–Meier method and log‐rank test were used to estimate the cumulative survival.ResultsAfter exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99).ConclusionResponse to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.

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Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi‐institutional analysis

Amirian,

Dickey,

Ogobuiro

et al. 2024

Journal of Surgical Oncology

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BackgroundIn patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing neoadjuvant therapy (NAT) and resection, selection of adjuvant chemotherapy (AC) is typically guided by high‐risk features on histopathologic examination. We evaluated the interaction between post‐NAT lymph node metrics and AC receipt on survival.MethodsPatients who received NAT followed by pancreatectomy (2010–2020) at seven centers were reviewed. Overall survival (OS) in patients receiving AC or not was stratified by lymph node positivity (LNP) or lymph node ratio (LNR) dichotomized at 0.1. Cox models evaluated the independent association between these nodal metrics, AC receipt, and OS.ResultsOf 464 patients undergoing NAT and resection, 264 (57%) received AC. Patients selected for AC were younger (median 63 vs. 67 years; p < 0.001), received shorter duration of NAT (2.8 vs. 3.2 months; p = 0.01), had fewer postoperative complications (Clavien–Dindo grade > 3: 1.2% vs. 11.7%; p < 0.001), and lower rates of pathologic complete response (4% vs. 11%; p = 0.01). The median number of nodes evaluated was similar between cohorts (n = 20 in both; p = 0.9). Post‐NAT LNP rates were not different, and median LNR was 0.1, in AC and non‐AC cohorts. Both LNP (hazard ratio [HR]: 2.1, p < 0.001) and LNR (0 < LNR ≤ 0.1: HR: 1.98, p = 0.002; LNR > 0.1: HR 2.46, p < 0.001) were independently associated with OS on Cox modeling, although receipt of AC was not associated with improved OS (median 30.6 vs. 29.4 months; p = 0.2). In patients with LNR > 0.1, receipt of AC was associated with significantly longer OS compared to non‐AC (24 vs. 20 months, respectively; p = 0.04).ConclusionsLNR following NAT, not simply nodal positivity, may be useful to refine selection of AC in resected PDAC.

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Lymph Node Ratio in Pancreatic Adenocarcinoma After Preoperative Chemotherapy vs. Preoperative Chemoradiation and Its Utility in Decisions About Postoperative Chemotherapy

Abstract: PCT is associated with a higher LNR and higher rates of node positivity than PCRT. Postoperative chemotherapy is associated with longer OS than observation in patients with a LNR of 0.01-0.149 after PCT.

Cited by 12 publications

References 46 publications

Adjuvant Chemotherapy Associated with Survival Benefit Following Neoadjuvant Chemotherapy and Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Population-Based Cohort Study

Adjuvant Chemotherapy Associated with Survival Benefit Following Neoadjuvant Chemotherapy and Pancreatectomy for Pancreatic Ductal Adenocarcinoma: A Population-Based Cohort Study

The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy

Lymph node metrics following neoadjuvant therapy to refine patient selection for adjuvant chemotherapy in resected pancreatic cancer: A multi‐institutional analysis

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