Does neoadjuvant treatment in resectable pancreatic cancer improve overall survival? A systematic review and meta-analysis of randomized controlled trials

Usón, Pedro Luiz Serrano; Silva, D Dias E; Castro, N M de; Victor, Elivane da Silva; Rother, Edna Terezinha; Araújo, Sérgio Eduardo Alonso; Borad, Mitesh J.; Moura, Fernando

doi:10.1016/j.esmoop.2022.100771

Cited by 18 publications

(12 citation statements)

References 34 publications

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“…The neoadjuvant treatments emerged as a feasible and pragmatic way to apply systemic treatment in patients with localized cancers [ 23 ]. The neoadjuvant treatments have significant advantages compared to the adjuvant setting, including the in vivo evaluation of drug sensitivity, improvement in the R0 resections, earlier eradication of the micrometastatic disease, and a higher chance for the completion of systemic treatment [ 24 , 25 , 26 , 27 ]. Using ICIs in the neoadjuvant setting could be more beneficial than in the adjuvant setting due to higher tumor neoantigen burden and intact lymphatic drainage before surgery.…”

Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer

Guven,

Sahin,

Kilickap

2023

Cancers

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Background: After the success of immunotherapy in the treatment of advanced non-small cell lung cancer (NSCLC), the benefit of neoadjuvant chemoimmunotherapy was compared with chemotherapy for localized NSCLC in several trials. However, the available studies had variable study designs, and study cohorts had limited follow-up times. Therefore, we conducted a systematic review and meta-analysis to evaluate the benefit of adding immunotherapy to neoadjuvant chemotherapy in patients with localized NSCLC. Methods: We conducted a systematic review using Pubmed, Web of Science, and Scopus databases for studies published until 5 December 2023. This protocol was registered in the PROSPERO database (Registration Number: CRD42023466337). We performed the meta-analyses with the generic inverse-variance method with a fixed effects model. Results: Overall, 7 studies encompassing 2993 patients were included in the analyses. The use of neoadjuvant chemoimmunotherapy was associated with a 41% reduction in the risk of progression or death compared to neoadjuvant chemotherapy (HR: 0.59, 95% CI: 0.52–0.66, p < 0.0001) and a lower risk of death (HR: 0.67, 95% CI: 0.55–0.82, p < 0.0001). The neoadjuvant chemoimmunotherapy improved pCR rates compared to chemotherapy (21.8% vs. 3.8%, OR: 7.04, 95% CI: 5.23–9.47, p < 0.0001), while high-grade adverse events were higher with neoadjuvant chemoimmunotherapy (OR: 1.18, 95% CI: 1.02–1.36, p = 0.0300). Conclusions: The available evidence demonstrates a statistically significant and clinically meaningful event-free survival benefit and possibly an overall survival benefit with neoadjuvant chemoimmunotherapy with a slight increase in high-grade toxicities.

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Section: Discussionmentioning

confidence: 99%

The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer

Guven,

Sahin,

Kilickap

2023

Cancers

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“…Mortality and morbidity of classical duodenopancreatectomy (Whipple’s procedure) have decreased in the last 15 years, and overall survival has also improved in surgical cases. Neoadjuvant treatments have increased the rate of operable PDACs [ 68 , 69 ]. This background justifies the search for a reliable screening method leading to what here we have called the “ultra” early detection.…”

Section: Diagnosis and Surgical Treatmentmentioning

confidence: 99%

Earlier Diagnosis of Pancreatic Cancer: Is It Possible?

Koltai

2023

Cancers

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Pancreatic ductal adenocarcinoma has a very high mortality rate which has been only minimally improved in the last 30 years. This high mortality is closely related to late diagnosis, which is usually made when the tumor is large and has extensively infiltrated neighboring tissues or distant metastases are already present. This is a paradoxical situation for a tumor that requires nearly 15 years to develop since the first founding mutation. Response to chemotherapy under such late circumstances is poor, resistance is frequent, and prolongation of survival is almost negligible. Early surgery has been, and still is, the only approach with a slightly better outcome. Unfortunately, the relapse percentage after surgery is still very high. In fact, early surgery clearly requires early diagnosis. Despite all the advances in diagnostic methods, the available tools for improving these results are scarce. Serum tumor markers permit a late diagnosis, but their contribution to an improved therapeutic result is very limited. On the other hand, effective screening methods for high-risk populations have not been fully developed as yet. This paper discusses the difficulties of early diagnosis, evaluates whether the available diagnostic tools are adequate, and proposes some simple and not-so-simple measures to improve it.

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“…Recent pooled analyses have shown that when compared to upfront surgery followed by AC, neoadjuvant chemotherapy (NAC) does not improve disease-free survival (DFS) or OS in patients with resectable PDAC. NAC has been reported to increase R0 rates by 20% 13 , 14 . The NEONAX trial found that patients with resectable PDAC treated with NAC and AC had a longer OS than those treated with AC alone, suggesting that neoadjuvant/perioperative treatment may be a viable alternative to AC for patients with resectable PDAC 15 .…”

Section: Introductionmentioning

confidence: 99%

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: A retrospective cohort study

Liu

et al. 2023

International Journal of Surgery

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Background: Patients with pancreatic ductal adenocarcinoma (PDAC) are increasingly receiving systemic neoadjuvant chemotherapy (NAC), particularly those with borderline resectable and locally advanced disease. However, the specific role of additional adjuvant chemotherapy (AC) in these patients is unknown. The objective of this study is to further assess the clinical benefit and impact of systemic AC in patients with resected PDAC after NAC. Methods: Data on PDAC patients with or without AC following systemic NAC and surgical resection were retrospectively retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2006 and 2019. A matched cohort was created using propensity score matching (PSM), and baseline characteristics were balanced to reduce bias. Overall survival (OS) and cancer-specific survival (CSS) were calculated using matching cohorts. Results: The study enrolled a total of 1,589 patients, with 623 (39.2%) in the AC group and 966 (51.8%) in the non-AC group (mean age, 64.0 [9.9] years; 766 [48.2%] were females and 823 [51.8%] were males). All patients received NAC, and among the crude population, 582 (36.6%) received neoadjuvant radiotherapy, while 168 (10.6%) received adjuvant radiotherapy. Following the 1:1 PSM, 597 patients from each group were evaluated further. The AC and non-AC groups had significantly different median OS (30.0 vs. 25.0 mo, P=0.002) and CSS (33.0 vs. 27.0 mo, P=0.004). After multivariate Cox regression analysis, systemic AC was independently associated with improved survival (P=0.003, HR=0.782; 95%CI, 0.667-0.917 for OS; P=0.004, HR=0.784; 95%CI, 0.663-0.926 for CSS), and age, tumor grade, and AJCC N staging were also independent predictors of survival. Only patients younger than 65 years old and those with a pathological N1 category showed a significant association between systemic AC and improved survival in the subgroup analysis adjusted for these covariates. Conclusion: Systemic AC provides a significant survival benefit in patients with resected PDAC following NAC compared to non-AC patients. Our study discovered that younger patients, patients with aggressive tumors and potentially well response to NAC might benefit from AC to achieve prolonged survival after curative tumor resection.

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Does neoadjuvant treatment in resectable pancreatic cancer improve overall survival? A systematic review and meta-analysis of randomized controlled trials

Cited by 18 publications

References 34 publications

The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer

The Efficacy and Safety of Neoadjuvant Immunotherapy in Patients with Non-Small Cell Lung Cancer

Earlier Diagnosis of Pancreatic Cancer: Is It Possible?

Survival benefit and impact of adjuvant chemotherapy following systemic neoadjuvant chemotherapy in patients with resected pancreas ductal adenocarcinoma: A retrospective cohort study

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