R0 Resection for Locally Advanced Pancreatic Cancer with Low-dose Gemcitabine with Wide Irradiation Area as Neoadjuvant Chemoradiotherapy

Kamachi, Hirofumi; Tsuruga, Yousuke; Orimo, Tatsuya; Wakayama, Kenji; Shimada, Shingo; Nagatsu, Akito; Yokoo, Hideki; Kamiyama, Toshiya; Katoh, Norio; Taketomi, Akinobu

doi:10.21873/invivo.11362

Cited by 8 publications

(5 citation statements)

References 34 publications

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“…Serum CA 19-9 levels are reportedly useful for perioperative management of patients with PDAC (16, 22), and the results of the present study suggest that patients with elevated Post-CA 19-9 levels are eligible for more intensive adjuvant or organ-specific treatment. Serum CA19-9 level is easy to monitor and has objective value, and prediction of elevated Post-CA19-9 levels can be helpful in selecting previously advocated preoperative treatments (23,24). In this patient series, high Pre-CA 19-9 levels supported preoperative treatment because of the increased risk of hepatic metastasis.…”

Section: Discussionmentioning

confidence: 75%

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer

et al. 2019

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Aim: In this study, we investigated the clinical significance of postoperative serum carbohydrate antigen (CA) 19-9 in patients with pancreatic ductal carcinoma (PDAC). Patients and Methods: A series of 116 patients with macroscopically curative PDAC resection was retrospectively evaluated. The cut-off level for elevated postoperative CA 19-9 was 37 U/ml. Results: Patients with high postoperative CA19-9 levels had a significantly poorer prognosis than patients with normal postoperative CA19-9 levels, as revealed by the logrank test. Multivariate analysis identified R1 resection and preoperative serum CA19-9 level ≥400 U/ml independently predicted elevated postoperative CA 19-9 levels. R1 resection and preoperative serum CA19-9 ≥400 U/ml were significantly associated with the recurrence of peritoneal dissemination and hepatic metastasis, respectively, within one year of operation. Conclusion: Elevated postoperative serum CA 19-9 level was associated with a poor prognosis and reflected positive resection margins and high preoperative CA 19-9 levels, which indicated presence of occult distant metastasis in patients with PDAC.Pancreatic ductal adenocarcinoma (PDAC) is highly lethal, and surgical resection is the only curative treatment available. The 5-year survival of patients with curative resection of PDAC has been estimated to be 20% (1). Adjuvant and neoadjuvant chemotherapies are offered in clinical practice aiming to improve survival (2-6). Accurate prediction of prognosis and effective stratification are important for planning postsurgical treatment and designing clinical trials. The prognostic value of carbohydrate antigen (CA) 19-9 has been evaluated in patients with PDAC following curative resection, and it reportedly reflects tumor burden (7, 8). High postoperative serum (Post)-CA 19-9 levels have been reported as a prognostic factor, and elevated Post-CA 19-9 levels were reported to be a more powerful prognostic factor than preoperative serum (Pre)-CA 19-9 (9-11) level. High Post-CA 19-9 levels have been considered to be associated with microscopically positive surgical margin or occult distant metastasis; however, their relationship has not been adequately and statistically confirmed yet (10-12). In the present study, we aimed to investigate the clinical significance of elevated Post-CA 19-9 levels by analyzing which factors are predictive of elevated Post-CA 19-9 levels. Patients and MethodsPatient population and study design. This retrospective cohort study evaluated patient data collected at the Tochigi Cancer Center. The protocol for this research project has been approved by a suitably constituted Ethics Committee of the institution and it conforms to the provisions of the Declaration of Helsinki.A series of 166 patients with surgical resection for PDAC between January 2008 and December 2016 were included in the analysis. Eleven patients with macroscopically positive resection margin or distant metastasis were excluded. Further, Pre-CA 19-9 was measured within 6 weeks of surgery. The lowest serum ...

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Section: Discussionmentioning

confidence: 75%

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer

et al. 2019

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“…In regards to low-dose gemcitabine, neoadjuvant chemoradiotherapy with a low dose of gemcitabine of 50–150 mg/m 2 per week has proved its effectiveness for locally advanced pancreatic cancer [ 42 , 43 , 44 , 45 ]. Various low doses of gemcitabine were administered for gemcitabine-based radiotherapy, and despite this low dose, excellent results were achieved.…”

Section: Discussionmentioning

confidence: 99%

Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer

Mori

Tanoue

Takaji

et al. 2022

Cancers

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(1) Background: Pretreatment by Rad51-inhibitory substances such as gemcitabine followed by arterial chemotherapy using antineoplastic agents causing DNA crosslink might be more beneficial for patients with locally advanced pancreatic cancers than conventional treatments. The efficacy of arterial administration of DNA crosslinking agents with pretreatment of intravenous low-dose gemcitabine for patients with unresectable locally advanced or metastatic pancreatic cancer (LAPC or MPC) is evaluated. (2) Methods: A single-arm, single-center, institutional review board-approved prospective study was conducted between 2005 and 2015. Forty-five patients (23 LAPC, 22 MPC) were included. Patients received a weekly low dose of gemcitabine intravenously for three weeks followed by arterial administration of mitomycin C and epirubicin hydrochloride at tumor-supplying arteries on the fifth or sixth week. This treatment course was repeated at 1.5-to-2-month intervals. Overall survival (OS), local progression-free survival (LPFS), and therapeutic response were evaluated. LAPC or MPC were divided according to treatment compliance, excellent or poor (1 or 2), to subgroups L1, L2, M1, and M2. (3) Results: OS of LAPC and MPC were 23 months and 13 months, respectively. The OS of LAPC with excellent treatment compliance (subgroup L1, 10 patients) was 33 months with 31 months of LPFS, and four patients (40%) had a complete response (CR). The OS of the L1 subgroup was significantly longer than those of other subgroups L2, M1, and M2, which were 17 months, 17 months, and 8 months, respectively. As Grade 3 adverse effects, severe bone marrow suppression, interstitial pneumonitis, and hemolytic uremic syndrome were observed in six (13.0%), three (6.5%), and three (6.5%) patients, respectively. (4) Conclusions: Arterial DNA crosslinking with the systemic restraint of homologous recombination repair can be a new treatment option for LAPC.

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“…Evans et al demonstrated that initially unknown micro-metastases might be eliminated by preoperative therapy (18). Moreover, a recent study showed that CRT with full-dose gemcitabine may have local and systemic effects in improving the R0 resection rate and reducing micrometastases (19). In this meta-analysis, only 24 out of 72 total patients (30.5%) in the neoadjuvant CRT group had positive LN compared to 72 out of 92 (78.3%) total patients with positive LN rate in the upfront surgery group.…”

Section: Discussionmentioning

confidence: 99%

Is neoadjuvant chemoradiotherapy for pancreatic cancer beneficial: A systematic review and meta-analysis

et al. 2022

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To examine the potential benefits and adverse events of neoadjuvant Chemoradiotherapy (CRT) versus upfront surgery in pancreatic cancer (PC) patients. Extensive librarian-led literature searches were conducted on PubMed, Web-of-Science, Scopus, Google Scholar, the Cochrane Central Library and Embase. The primary outcomes were resectability, adverse events, pathological and survival outcomes. Five studies, including 437 participants, were analyzed. Upfront surgery had a significantly higher resectability among PC patients than neoadjuvant CRT group (Odds ratio = -0.11, 95% CI = -0.19–0.02, P = 0.01). The neoadjuvant CRT group had a comparatively higher Ro resection rate (OR = 3.38, 95% CI = 2.03–5.62, P < 0.01), fewer severe adverse events(OR = 0.56, 95% CI = 0.34–0.92, P = 0.02), lower positive LN rate(OR = 0.18, 95% CI = 0.11-0.31, P < 0.01) and higher 2-year OS(OR = 1.60, 95% CI = 1.02-2.52, P = 0.04) among PC patients than control group. There was no significant difference between neoadjuvant CRT and upfront surgery among PC patients on postoperative complications(OR = 1.49, 95% CI = 0.86-2.57, P = 0.16), metastasis rate(OR = 1.32, 95% CI = 0.42-4.18, P = 0.64) and 1-year OS(OR = 1.30, 95% CI = 0.85-1.98, P = 0.22). This systematic review confirmed the status of neoadjuvant CRT in the PC treatment. The neoadjuvant CRT could increase the R0 resection rate, which was important to the survival and life quality of patients. The specific choice of various neoadjuvant CRT therapy needs to be further studied. Individualized neoadjuvant therapy should be suitable for each patient, and patients with PC are best managed by a multidisciplinary team.

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R0 Resection for Locally Advanced Pancreatic Cancer with Low-dose Gemcitabine with Wide Irradiation Area as Neoadjuvant Chemoradiotherapy

Abstract: NACRT with low-dose gemcitabine and wide irradiation area achieved 100% R0 resection and acceptable prognosis.

Cited by 8 publications

References 34 publications

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer

Predictive Factors for Elevated Postoperative Carbohydrate Antigen 19-9 Levels in Patients With Resected Pancreatic Cancer

Arterial Administration of DNA Crosslinking Agents with Restraint of Homologous Recombination Repair by Intravenous Low-Dose Gemcitabine Is Effective for Locally Advanced Pancreatic Cancer

Is neoadjuvant chemoradiotherapy for pancreatic cancer beneficial: A systematic review and meta-analysis

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