Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy

Wijetunga, Asanka; Chua, Terence C.; Nahm, Christopher B.; Pavlakis, Nick; Clarke, Stephen; Chan, David; Diakos, Connie I.; Maloney, Sarah; Ashrafizadeh, Amir; Kneebone, Andrew; Hruby, George; Jamieson, Nigel B.; Gill, Anthony J.; Mittal, Anubhav; Samra, Jaswinder S.

doi:10.1016/j.ejso.2021.04.005

Cited by 10 publications

(14 citation statements)

References 23 publications

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“…Similarly, we found most patients experienced a reduction in CA19-9 levels after treatment, and the CA19-9 response was an independent prognostic factor for outcomes of patients in our study. Moreover, we found that more chemotherapy cycles were associated with better survival, which were in line with previous findings ( 36 , 37 ). Similar findings were also indicated in other types of tumor such as gastric cancer.…”

Section: Discussionsupporting

confidence: 93%

Use of Nab-Paclitaxel Plus Gemcitabine Followed by Hypofractionated Tomotherapy With Simultaneous Integrated Boost in Patients With Locally Advanced Pancreatic Cancer

et al. 2022

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Background and PurposeA phase 2 study LAPACT indicated nab-paclitaxel plus gemcitabine (AG) improved outcomes of patients with locally advanced pancreatic cancer (LAPC). Conventional radiotherapy failed to show benefit, indicating high dose to volume with high risk of recurrence is needed. The high dose can be delivered through hypofractionated tomotherapy with simultaneous integrated boost (SIB). However, there is a lack of such prospective trials and more data are needed to validate the role of AG plus hypofractionated tomotherapy with SIB in patients with LAPC.Materials and MethodsPatients with LAPC receiving AG plus tomotherapy at the Nanjing Drum Tower Hospital between 2018 and 2021 were retrospectively analyzed. The treatment was scheduled as follows: nab-paclitaxel 125 mg/m2 plus gemcitabine 1,000 mg/m2 on days 1 and 8 every three weeks for at least two cycles, followed by hypofractionated tomotherapy with SIB (high dose field: 50 Gy/10 fractions, the remainder: 30 Gy/10 fractions). Then patients were given AG until intolerance or disease progression.ResultsOverall, 22 patients completing the chemoradiotherapy were included. The median follow-up was 15.2 months. After the chemoradiotherapy, 5 patients achieved a partial response (PR), 15 had a stable disease (SD), and another 2 patients were with progressive disease (PD). The median progression-free survival (PFS) and overall survival (OS) were 12.8 months (95% confidence interval [CI] 4.3–21.3 months) and 16.3 months (95% CI 10.9–21.6 months), respectively. The optimal carbohydrate antigen (CA) 19-9 response and chemotherapy cycles ≥6 were correlated with favorable PFS and OS. The most common recurrent pattern was peritoneal dissemination (22.7%) and the locoregional recurrence rate was relatively low (4.5%). Treatments were well-tolerated. The most common grade ≥3 adverse event was thrombocytopenia (13.6%).ConclusionThis study demonstrated the feasibility of AG followed by hypofractionated tomotherapy with SIB in patients with LAPC. The hypofractionated tomotherapy with SIB was safe and showed high local control rate. Further study with a larger population to validate our data is underway.

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Section: Discussionsupporting

confidence: 93%

Use of Nab-Paclitaxel Plus Gemcitabine Followed by Hypofractionated Tomotherapy With Simultaneous Integrated Boost in Patients With Locally Advanced Pancreatic Cancer

et al. 2022

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“…A crucial point in the management of LAPC is the selection, through the identification of prognostic and predictive factors, of patients with more chances to benefit from a multimodal treatment, including surgery for responsive patients. Indeed, patients who respond to chemotherapy probably have a favorable disease biology and should be selected for more aggressive upfront management and surgery, while patients with resistant disease should be spared from high-risk surgery [38]. In the present study, we identified baseline CA19-9 and ECOG PS as prognostic factors and CA19-9 as the only predictor for resection.…”

Section: Discussionmentioning

confidence: 65%

Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies

et al. 2021

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In locally advanced pancreatic cancer (LAPC), the combination of chemotherapy and radiotherapy is a widely used treatment option. We performed a pooled analysis, including an exploratory analysis for prognostic and predictive factors, of two phase 2 trials including 73 patients with LAPC, treated with gemcitabine and oxaliplatin (GEMOX) and hypofractionated tomotherapy. With a median follow-up of 36 months (range 1–65), median progression-free (PFS) and overall survival (OS) were 10.2 (95% confidence interval [CI] 7.8–13.2) and 14.3 (95% CI 12.0–18.1) months, respectively. The overall resectability rate was 23.3% (95% CI 13.6–33.0), and the R0 resection rate was 13.7% (95% CI 5.8–21.6). In the multivariate analysis, ECOG performance status (PS) 0 and low levels of CA 19–9 were associated with improved OS and PFS. Concerning OS, log(CA19–9) resulted in a hazard ratio (HR) of 1.20 (95% CI 1.02–1.42), p = 0.027. For ECOG PS 0, HR was 1.00; for PS 1, HR was 2.69 (95% CI 1.46–4.96); for PS 2, HR was 4.18 (95% CI 0.90–19.46); p = 0.003. Low CA19–9 levels were also predictive for resection, with an odds ratio of 0.71 (95% CI 0.52–0.97), p = 0.034. In conclusion, GEMOX and hypofractionated radiotherapy is a treatment option in LAPC. Further studies are needed to identify differences in tumor biology, which may help to predict resectability and prognosis.

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“…If we would use the date of diagnosis as reference, there would be a significant difference in survival curves between the use or not of NACHT determined by the log rank test (see Additional file 1 ). Studies using the date of diagnosis as reference but only including the patients who underwent surgery tended to show a positive effect of NACHT such as in the study from the Mayo Clinic in which an association was described between extended duration of NACHT for BR and LA with response and survival [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

de Carvalho,

Gryspeerdt,

Rashidian

et al. 2023

BMC Surg

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Background The treatment of borderline resectable (BR) and locally advanced (LA) pancreatic ductal adenocarcinoma (PDAC) has evolved with a wider application of neoadjuvant chemotherapy (NACHT). The aim of this study was to identify predictive factors for survival in BR and LA PDAC. Methods Clinicopathologic data of patients with BR and LA PDAC who underwent surgical exploration between January 2011 and June 2021 were retrospectively collected. Survival from the date of surgery was estimated using the Kaplan-Meier method. Simple and multiple Cox proportional hazards models were fitted to identify factors associated with survival. Surgical resection was analyzed in combination with the involvement of lymph nodes as this last was only known after a formal resection. Results Ninety patients were surgically explored (BR: 45, LA: 45), of which 51 (57%) were resected (BR: 31, LA: 20). NACHT was administered to 43 patients with FOLFIRINOX being the most frequent regimen applied (33/43, 77%). Major complications (Clavien-Dindo grade III and IV) occurred in 7.8% of patients and 90-day mortality rate was 3.3%. The median overall survival since surgery was 16 months (95% CI 12-20) in the group which underwent surgical resection and 10 months (95% CI 7-13) in the group with an unresectable tumor (p=0.001). Cox proportional hazards models showed significantly lower mortality hazard for surgical resection compared to no surgical resection, even after adjusting for National Comprehensive Cancer Network (NCCN) classification and administration of NACHT [surgical resection with involved lymph nodes vs no surgical resection (cHR 0.49; 95% CI 0.29-0.82; p=0.007)]. There was no significant difference in survival between patients with BR and LA disease (cHR= 1.01; 95% CI 0.63-1.62; p=0.98). Conclusions Surgical resection is the only predictor of survival in patients with BR and LA PDAC, regardless of their initial classification as BR or LA. Our results suggest that surgery should not be denied to patients with LA PDAC a priori. Prospective studies including patients from the moment of diagnosis are required to identify biologic and molecular markers which may allow a better selection of patients who will benefit from surgery.

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Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy

Cited by 10 publications

References 23 publications

Use of Nab-Paclitaxel Plus Gemcitabine Followed by Hypofractionated Tomotherapy With Simultaneous Integrated Boost in Patients With Locally Advanced Pancreatic Cancer

Use of Nab-Paclitaxel Plus Gemcitabine Followed by Hypofractionated Tomotherapy With Simultaneous Integrated Boost in Patients With Locally Advanced Pancreatic Cancer

Multimodal Treatment with GEMOX Plus Helical Tomotherapy in Unresectable Locally Advanced Pancreatic Cancer: A Pooled Analysis of Two Phase 2 Studies

Predictive factors for survival in borderline resectable and locally advanced pancreatic cancer: are these really two different entities?

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