Impact of modified physiobiological parameter-based grading system on long-term prognosis for resectable pancreatic cancer following curative surgery

14004 Background: Gemcitabine (GEM) is recognized as an effective chemotherapeutic agent for non-curative pancreatic cancer and has an activity for radiosensitizer. Although preoperative chemoradiation therapy (preCRT) with GEM is one of the promising adjuvant therapies for potentially curative pancreatic cancer, the clinical significance of the treatment remains to obscure. Methods: Potentially resectable pancreatic cancer patients were recruited in this study from September 2001 through August 2004. Patients were randomly divided into preCRT group and a control group. Patients in preCRT group received GEM (400 mg/m2 or 800 mg/m2 on day 1 and 7) and concomitant accelerated hyperfractionated irradiation (1.5 Gy ×2/day, 5 days/weeks, total dose 30Gy or 36 Gy). After 3–4 weeks’ rest of the preCRT, patients were re-evaluated for resectability. Patients who underwent R0 resection did not received any postoperative adjuvant treatment until recurrence. Results: There were 23 patients in preCRT group and were 19 patients in control group. After re-evaluation, 4 patients (17%) were considered as unresectable due to the progressed disease. 19 patients (83%) in preCRT group and 19 patients (100%) in control group underwent laparotomy. Sixteen patients (70%) in preCRT group and 17 patients (89%) in control group underwent R0 resection. Median survival times were 17.6 months in preCRT group and 16.7 months in control group, respectively (p=0.65). Among patients underwent R0 resection, one and three-years survival rate were 81.2% and 27.1% in preCRT group, while these were 70.6% and 15.4% in the control group (p=0.26). Local recurrence was observed in 4 (25%) of 16 patients who underwent R0 resection in preCRT group and in 7 (41%) of 17 patients who underwent R0 resection in control group, while recurrence at distant organs (liver, lung, peritoneum, bone) were observed in 8 patients (50%) of preCRT group and 8 patients (47%) in control group. Conclusions: Although the preoperative chemoradiation therapy with GEM and accelerated hyperfractionated radiation for potentially curative pancreatic cancer is likely to be promising against local recurrence after R0 resection, survival benefit of the therapy was unsatisfactory. No significant financial relationships to disclose.

Download Full-text

Neoadjuvant Treatment Strategies in Resectable Pancreatic Cancer

Cancers ◽

10.3390/cancers13184724 ◽

2021 ◽

Vol 13 (18) ◽

pp. 4724

Author(s):

Aurélien Lambert ◽

Lilian Schwarz ◽

Michel Ducreux ◽

Thierry Conroy

Keyword(s):

Pancreatic Cancer ◽

Randomized Trials ◽

Neoadjuvant Treatment ◽

Treatment Strategies ◽

Main Concern ◽

Resectable Pancreatic Cancer ◽

Curative Surgery ◽

Curative Therapy ◽

Risk Of Disease ◽

Meta Analyses

Complete surgical resection is the cornerstone of curative therapy for resectable pancreatic adenocarcinoma. Upfront surgery is the gold standard, but it is rarely curative. Neoadjuvant treatment is a logical option, as it may overcome some of the limitations of adjuvant therapy and has already shown some encouraging results. The main concern regarding neoadjuvant therapy is the risk of disease progression during chemotherapy, meaning the opportunity to undergo the intended curative surgery is missed. We reviewed all recent literature in the following areas: major surveys, retrospective studies, meta-analyses, and randomized trials. We then selected the ongoing trials that we believe are of interest in this field and report here the results of a comprehensive review of the literature. Meta-analyses and randomized trials suggest that neoadjuvant treatment has a positive effect. However, no study to date can be considered practice changing. We considered design, endpoints, inclusion criteria and results of available randomized trials. Neoadjuvant treatment appears to be at least a feasible strategy for patients with resectable pancreatic cancer.

Download Full-text

Trends in survival based on treatment modality in patients with pancreatic cancer: a population-based study

Current Oncology ◽

10.3747/co.27.5211 ◽

2020 ◽

Vol 27 (1) ◽

Cited By ~ 1

Author(s):

S. Shakeel ◽

C. Finley ◽

G. Akhtar-Danesh ◽

H. Y. Seow ◽

N. Akhtar-Danesh

Keyword(s):

Pancreatic Cancer ◽

Treatment Modality ◽

Survival Rates ◽

Population Based ◽

Parametric Models ◽

Stage I ◽

Analysis Survival ◽

Long Term Prognosis ◽

Over Time

Background Pancreatic cancer (PC) is one of the most lethal types of cancer and surgery remains the most optimal treatment modality for patients with resectable tumors. The objective of this study is to examine and compare the trends in survival rate among PC patients based on treatment modality.Methods This population-based retrospective analysis included all patients with known stage for PC in Ontario, Canada between 2007 and 2015. Flexible parametric models were used to conduct survival analysis. Survival rates were calculated based on treatment modality, while adjusting for patient and tumor specific covariates.Results In total, 6437 patients were included in this study. More than half of the patients aged 80 and over received no curative treatment. The proportion of patients receiving chemoradiation decreased over time. The 1-, 2- and 5-year survival rates increased 30-40% for stage I disease and less than 15% for stage II over the study period. Noticeable increases in 1-, 2, and 5-year survival rates were observed for patients underwent for distal pancreatectomy and Whipple procedures. There were no changes in survival for stage III and IV disease from 2007 to 2015.Conclusions A majority of cases for PC continue to be diagnosed in late stage, with poor short-term and long-term prognosis. The survival for stage I tumors and surgical modalities increased over time without any evidence of changes in stage distribution. We speculate that improvements in chemotherapy modalities and adoption of quality standards for surgical resection could be attributed for the positive trends in survival.

Download Full-text

Phase I/II trial of neoadjuvant chemoradiotherapy with 5-FU, cisplatin, mitomycin C, and heparin for borderline resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.315 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 315-315

Author(s):

Taizo Hibi ◽

Minoru Kitago ◽

Koichi Aiura ◽

Minoru Tanabe ◽

Osamu Itano ◽

...

Keyword(s):

Pancreatic Cancer ◽

Mitomycin C ◽

Curative Resection ◽

Neoadjuvant Chemoradiotherapy ◽

Advanced Pancreatic Cancer ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Borderline Resectable Pancreatic Cancer ◽

Disease Free

315 Background: Because of the high incidence of local recurrence and liver metastasis, long-term outcomes of patients following resection of advanced pancreatic cancer are extremely poor. Facilitation of curative resection and prevention of micrometastasis are the goals of neoadjuvant therapy. We evaluated the feasibility and efficacy of our neoadjuvant chemoradiotherapy (NACRT) protocol for borderline resectable pancreatic cancer patients. Methods: During the period between 2003 and 2011, 24 patients with borderline resectable pancreatic cancers underwent NACRT comprising 5-FU (300 mg/body/day, day 1−5/week for 4 weeks), cisplatin (10mg/body day2, 9, 16, 23), mitomycin C (4mg/body/day, day 1, 8, 15, and 22), heparin (6000 IU/body/day for 4 weeks), and radiation (2 Gy/day, day 1−5/week for 4 weeks, total 40 Gy). They were reevaluated for resectability after therapy. Primary endpoints were toxicity and overall patient and disease-free survivals. Secondary endpoint was the ratio of microscopically margin negative resection. Results: All 24 patients completedNACRT. Grade 3−4 hematological adverse events were observed in 9 (38%) patients but none developed severe gastrointestinal toxicity. In 7 (29%) patients, restaging revealed distant metastasis or local disease progression not amenable to curative resection. The remaining 17 patients (71%) underwent surgery (pancreatoduodenectomy, 13 and distal pancreatectomy, 4) with zero 30-day postoperative or in-hospital mortality. The 5-year overall all patient and disease-free survival rates after pancreatectomy were 52.6% and 36.3%, respectively. Postoperative histopathological evaluation demonstrated a marked degenerative change in the specimen, achieving negative surgical margins in 15/17 (88%) patients and pathological complete response in the remaining 2 (12%) patients. Conclusions: Our NACRT protocol is feasible with a low toxicity profile and an excellent curative resection rate in the treatment of borderline resectable pancreatic cancer. It is a promising regimen associated with improved long-term prognoses than historical controls.

Download Full-text

Perioperative and long-term impact of neoadjuvant chemoradiotherapy using full-dose gemcitabine and concurrent radiation for resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.367 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 367-367

Author(s):

Minako Nagai ◽

Takahiro Akahori ◽

Satoshi Nishiwada ◽

Kenji Nakagawa ◽

Kota Nakamura ◽

...

Keyword(s):

Pancreatic Cancer ◽

Neoadjuvant Chemoradiotherapy ◽

Control Group ◽

Poor Performance Status ◽

Resectable Pancreatic Cancer ◽

Borderline Resectable ◽

Full Dose ◽

Venous Involvement ◽

The Impact

367 Background: Although much attention has been paid to neoadjuvat treatment for pancreatic cancer (PC), its efficacy remains to be established. In this study, we have retrospectively evaluated the impact of neoadjuvant chemoradiotherapy (NACRT) on perioperative and long-term clinical outcome in PC. Methods: One hundred sixty patients who preoperatively received full-dose gemcitabine (1000 mg/m2) with concurrent radiation of 54 Gy between 2006 and 2016 were analyzed. One hundred thirty patients who underwent upfront surgery were served as control. Results: Among the 160 patients treated with NACRT, 153 patients (96%) completed the protocol treatment. The reasons of failure to complete NACRT were drug-induced pneumonia, acute mucosal injury, severe cholangitis and poor performance status (PS). Furthermore 21 (13%) couldn’t undergo pancreatic resection after NACRT because of distant metastasis in 9 patients, tumor progression in 7 and poor PS in 5. The rate of pancreatic fistula was lower and hospital stay was shorter in the NACRT group compared to the control group (P = 0.033, P = 0.002). Furthermore, the rate of lymph node metastasis, R0 resection and pathological stage were favorable in the NACRT group (P < 0.0001, P = 0.006, P < 0.0001). The completion rate of adjuvant chemotherapy was also higher in the NACRT group (P = 0.015). Importantly, patients treated with NACRT had a better prognosis than those without (median survival time: 60.2 vs. 28.5M, P = 0.008). In addition, according to tumor resectability status, patients were classified as R (resectable), BR-P (borderline resectable with venous involvement) and BR-A (borderline resectable with arterial involvement) groups. As a result, patients treated with NACRT had a better prognosis than those without in the R and BR-P groups (58.6 vs. 34.2M, P = 0.013, 62.4 vs. 18.8M, P = 0.015), while NACRT had no significant impact on prognosis in the BR-A group. Conclusions: Neoadjuvant chemoradiotherapy may have a variety of favorable impact in pancreatic cancer treatment. Furthermore, NACRT may improve the prognosis especially in resectable and borderline resectable pancreatic cancer with venous involvement.

Download Full-text

Role of para-aortic lymph node sampling in pancreatic cancer surgery.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.715 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 715-715

Author(s):

Yusuke Kazami ◽

Hiromichi Ito ◽

Yoshihiro Ono ◽

Takafumi Sato ◽

Yosuke Inoue ◽

...

Keyword(s):

Pancreatic Cancer ◽

Lymph Node ◽

Pancreatic Resection ◽

Pancreatic Head ◽

Imaging Study ◽

Resectable Pancreatic Cancer ◽

Lymph Node Sampling ◽

Aortic Lymph Node

715 Background: In the management of pancreatic cancer, para-aortic lymph node (PALN) metastasis is regarded as distant metastasis, and systemic treatment is recommended. However, imaging study is not perfect to detect all PALN metastasis and the management of intraoperatively discovered PALN has been controversial. We hypothesized that sampling of PALNs on exploration could allow us to avoid pancreatic resection for patients who would not benefit. In this study, we evaluated the incidence and the effect on the long-term outcomes for patients with potentially resectable pancreatic cancer. Methods: Three hundred and ninety-two patients who had PALNs sampled upon potentially resectable pancreatic cancer from 2005 through 2014 were included in the study. All patients were appropriately staged preoperatively with CT/MRI and those with suspected PALN metastasis were not considered as candidates for resection. The patients whose resections were aborted because of liver metastasis or peritoneal dissemination discovered on exploration, or those who died within 30-days after the operation were not included. Evaluated outcomes were incidence of PALN metastasis and their recurrence-free and overall survivals (RFS, OS). Results: The patients’ median age was 74 years, and 58.6% was man. 67.8% had tumors at pancreatic head. Preoperative chemotherapy was given only on 16 patients (3.2%). Among 392 patients with PALNs sampled, 53 (13.5%) patients had metastasis; Resection was completed on 40 patients and resection was aborted on the rest. Among patients who underwent pancreatic resection, median RFS and OS were 10 and 12 months for patients with PALN metastasis, compared to 17 and 26 months for those without PALN metastasis (p < 0.001 for RFS and p < 0.001 for OS). The 5-year-OS rates for patients with/without PALN metastasis were 5.9% and 25% (p < 0.001). Among 53 patients with PALN metastasis, OS were not different between the patients who underwent resection and those who did not (median 13 months vs 17 months, p = 0.06), and there were no recurrence-free survivors. Conclusions: PALN sampling and evaluation before committing to resection is useful to identify the patients who can unlikely benefit and to avoid unnecessary morbid operation.

Download Full-text