Local treatment of pancreatic cancer metastases: A multicenter French study of the AGEO group

Objectives: To evaluate the role of stereotactic body radiotherapy (SBRT) as a local ablative treatment (LAT) in oligometastatic pancreatic cancer. Methods: Patients affected by histologically confirmed stage IV pancreatic adenocarcinoma were included in this analysis. Endpoints are local control (LC), progression-free survival (PFS), and overall survival (OS). Results: From 2013 to 2017, a total of 41 patients were treated with SBRT on 64 metastases. Most common sites of disease were lung (29.3%) and liver (56.1%). LC at 1 and 2 years were 88.9% (95% CI 73.2–98.6) and 73.9% (95% CI 50–87.5), respectively. Median LC was 39.9 months (95% CI 23.3—not reached). PFS rates at 1 and 2 years were 21.9% (95% CI 10.8–35.4) and 10.9% (95% CI 3.4–23.4), respectively. Median PFS was 5.4 months (95%CI 3.1–11.3). OS rates at 1 and 2 years were 79.9% (95% CI 63.7–89.4) and 46.7% (95% CI 29.6–62.2). Median OS was 23 months (95%CI 14.1–31.8). Conclusions: Our results, although based on a retrospective analysis of a small number of patients, show that patients with oligometastatic pancreatic cancer may benefit from local treatment with SBRT. Larger studies are warranted to confirm these results. Advances in knowledge: Selected patients affected by oligometastatic pancreatic adenocarcinoma can benefit from local ablative approaches, like SBRT

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The role of local treatment for the recurrence of pancreatic cancer after pancreatectomy

Pancreatology ◽

10.1016/j.pan.2016.06.358 ◽

2016 ◽

Vol 16 (4) ◽

pp. S100

Author(s):

Daisuke Ban ◽

Yasuhito Iwao ◽

Yoshiya Ishikawa ◽

Shuichi Watanabe ◽

Yuki Mizuno ◽

...

Keyword(s):

Pancreatic Cancer ◽

Local Treatment

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The Molecular Connections between Lung and Pancreatic Cancer Metastases: are we not seeing the Forest for the Trees?

Journal of Cancer Prevention & Current Research ◽

10.15406/jcpcr.2017.07.00242 ◽

2017 ◽

Vol 7 (4) ◽

Author(s):

Angelo Wilson

Keyword(s):

Pancreatic Cancer ◽

Cancer Metastases

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Use of cell therapy as a means of targeting chemotherapy to inoperable pancreatic cancer.

Acta Biochimica Polonica ◽

10.18388/abp.2005_3420 ◽

2005 ◽

Vol 52 (3) ◽

pp. 601-607 ◽

Cited By ~ 9

Author(s):

Walter H Günzburg ◽

Brian Salmons

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Cytochrome P450 ◽

Local Treatment ◽

Solid Tumours ◽

Drug Status ◽

Cytochrome P450 Enzyme ◽

Encapsulated Cells ◽

Cell Based Therapy

Although approved for the treatment of pancreatic cancer, the chemotherapeutic agent ifosfamide is not an effective therapy for this type of tumour. Ifosfamide must be activated by cytochrome P450 (P450) enzymes in the liver, initially to a short lived intermediate and then to toxic metabolites that are subsequently distributed by the circulatory system. Particularly for pancreatic cancer, this liver-mediated conversion results in relatively high systemic toxicities and poor therapeutic concentrations at the liver-distant site of the tumour. Activation of ifosfamide at the site of the tumour may allow lower doses to be used, while increasing the therapeutic index due to the resultant active concentrations generated locally. A cell-based therapy has been conceived where encapsulated, 293-derived cells genetically modified to overexpress a cytochrome P450 enzyme, are implanted near solid tumours. The cells are encapsulated in polymers of cellulose sulphate in order to provide a means of immunoprotection in vivo as well as to physically constrain them to the vicinity of the tumour. A major advantage of this strategy is that it allows one standard cell line to be applied to all patients and this approach can be extended to the treatment of other tumour types. After proof of principle studies in animal models, a phase I/II clinical trial was initiated in patients with stage III/IV nonresectable pancreatic cancer. Encapsulated cells were angiographically placed into the tumour vasculature of 14 patients and followed by systemic low dose ifosfamide treatment. Angiographic delivery of encapsulated cells proved feasible in all but one patient, and was well tolerated with no capsule or ifosfamide treatment-related adverse events. Four of the treated patients showed tumour regressions after capsule delivery and ifosfamide treatment in computer-tomography scans. The other 10 patients showed no further tumour growth (i.e. stable disease) during 20 weeks observation period. The median life expectancy of the patient collective was extended two fold as compared to age and status matched historical controls, with a 3-fold improvement in one year survival being attained. Evidence for a clinical benefit of the treatment was also obtained on the basis of standard parameters for quality of life. This approach has been evaluated by the European Medicines Evaluation Agency (EMEA) and orphan drug status has been granted. A pivotal clinical trial is now being planned with the help of the EMEA. Taken together, the data from this clinical trial suggest that encapsulated cytochrome P450-expressing cells combined with chemotherapy may be useful for the local treatment of a number of solid tumours and support the performance of further clinical studies of this new treatment.

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Combined treatment of patients with localized pancreatic cancer of elderly and senile age

Medical Council ◽

10.21518/2079-701x-2021-9-122-128 ◽

2021 ◽

pp. 122-128

Author(s):

L. I. Moskvicheva ◽

L. V. Bolotina ◽

A. L. Kornietskaya ◽

D. V. Sidorov ◽

N. A. Grishin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Survival Rate ◽

Pancreatic Adenocarcinoma ◽

Combined Treatment ◽

Local Treatment ◽

Progression Free Survival ◽

The Elderly ◽

Medical Apparatus ◽

Free Survival ◽

Oncology Research

Introduction. The gold standard for the treatment of patients with a localized form of pancreatic cancer is radical surgical intervention. It is characterized by a high frequency of postoperative complications and is not performed in patients with a weakened general functional status and the presence of multiple severe concomitant somatic pathology.Purpose. The aim of this study is a assessment of the safety and effectiveness of combined treatment with the inclusion of gemcitabine chemotherapy and HIFU therapy in somatically inoperable patients with localized pancreatic adenocarcinoma of the elderly and senile age.Materials and methods. This study involved 15 patients with stage II (T3N0-1M0) disease aged 60 years and older, with a performance status ECOG 2 and a high operational and anesthetic risk, who received palliative combined treatment on the basis of the P. Hertsen Moscow Oncology Research Institute in the period from 2017 to 2020. HIFU therapy was performed on the HIFU2001 (Shenzhen Huikang Medical Apparatus Co., Ltd.), local treatment sessions were carried out in the amount of 3–8 per course, conducted daily, in the intervals between days of intravenous administration of gemcitabine at a dosage of 1000 mg/m2 (1, 8, 15 days every 4 weeks).Results. Adverse events of systemic drug therapy were observed in 9 (60%) patients, local complications of HIFU therapy — in 6 (37.5%) patients. 6 months after the start of treatment, pain control was achieved in 87.5% of patients, local progression of the disease was detected in 2 (13.3%) cases, and a partial tumor response was determined in 2 patients and stable disease in 11 patients. The median overall survival was 19 months, and the median progression-free survival was 12 months. The overall 1-, 2-, and 3-year survival rate was 80%, 20%, and 13%, respectively, and the 1-year progression-free survival rate was 54%.Conclusions. The results of this study demonstrate the prospects of using a combination of HIFU therapy and gemcitabine monotherapy in somatically inoperable patients with localized pancreatic adenocarcinoma of the elderly and senile age.

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Fe2P nanorods based photothermal therapy combined with immune checkpoint inhibitors for pancreatic cancer

Nanophotonics ◽

10.1515/nanoph-2021-0196 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Shanshan Liu ◽

Jiawen He ◽

Ruixiang Song ◽

Mengmeng Zhang ◽

Lianghao Huang ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Death ◽

Photothermal Therapy ◽

Pancreatic Tumor ◽

Local Treatment ◽

Advanced Pancreatic Cancer ◽

Tumor Model ◽

Pancreatic Tumors ◽

Tumor Cell Death ◽

Primary Tumors

Abstract Treatment of pancreatic cancer is faced with great difficulties and challenges due to high lethality and metastasis. Synergism of targeted therapy and immunotherapy has been considered as ideal strategy to both eliminate primary tumors and control metastases. For the treatment of advanced pancreatic cancer, we demonstrated a local photothermal therapy (PTT) following administration of monoclonal antibody of programmed death ligand 1 (αPD-L1). Fe2P nanorods were employed as a Fenton agent and photothermal agent, which modified with DSPE-PEG2000-Mal for improved biocompatibility and Mal mediated-antigen presentation. Under a low dose laser irradiation at 980 nm, Fe2P-PEG-Mal nanorods (NRs) mediated PTT could induce immunogenic tumor cell death that can cause dendritic cells (DCs) infiltration and maturation. In a bilateral pancreatic tumor model, the local treatment of NRs-PTT on primary tumor could cause the increased infiltration of cytotoxic T lymphocytes (CTLs) and decreased residential of M2 macrophages in untreated distal tumors. Furthermore, subsequently intervened αPD-L1 could enhance cell death triggered by CTLs in distal tumors through reversing immunosuppression. An orthotopic pancreatic tumor model was used to further confirm the therapeutic outcome. Finally, the combination of NRs based PTT and αPD-L1 based immunotherapy was able to significantly eliminate orthotopic pancreatic tumors and reduce mesentery metastases. Thus, the strategy may provide a more effective treatment for pancreatic cancer.

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Phase II study of neoadjuvant chemotherapy with modified FOLFOXIRI in borderline resectable or unresectable stage III pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.4062 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 4062-4062 ◽

Cited By ~ 2

Author(s):

Enrico Vasile ◽

Nelide De Lio ◽

Carla Cappelli ◽

Luca Pollina ◽

Niccola Funel ◽

...

Keyword(s):

Pancreatic Cancer ◽

Surgical Resection ◽

Phase Ii ◽

Locally Advanced ◽

Local Treatment ◽

Stage Iii ◽

Borderline Resectable ◽

Term Outcome ◽

Long Term Outcome ◽

Radical Surgical Resection

4062 Background: FOLFIRINOX has shown high activity in metastatic pancreatic cancer (PC) patients and could be an interesting regimen also for patients with inoperable locally advanced disease. Our group had developed a similar schedule in metastatic colorectal cancer named FOLFOXIRI with good tolerance and activity. Therefore, we have decided to perform a phase II trial to prospectively evaluate the activity of modified FOLFOXIRI in borderline resectable or unresectable PC. Methods: Modified FOLFOXIRI consisted of a lower dose of irinotecan (150 mg/sqm) and of infusional 5-fluorouracil (2800 mg/sqm as a 48-hour continuous infusion on days 1 to 3) with no bolus 5-fluorouracil. Folinic acid and oxaliplatin (85 mg/sqm) remained unchanged. The study enrolled patients with diagnosis of pancreatic adenocarcinoma, stage III borderline resectable or unresectable disease (cT4,cN0-1,cM0), ECOG PS 0-1, age 18-75. The primary end-point of the study was the percent of patients who undergo radical surgical resection after chemotherapy. Results: Thirty-two patients have been enrolled; M/F=12/20; PS 0/1=16/16. Median age was 60 years (range 44-75). Median number of FOLFOXIRI cycles was 6 (range 2-14). Grade 3-4 toxicities was experienced by 20 patients during chemotherapy. Twelve partial responses (37%) and 14 stable diseases (45%) have been observed; 2 patients had progressive diseases (6%). The remaining 4 patients (12%) have not been yet evaluated because are still in the first months of treatment. A local treatment was received after chemotherapy by 18 patients until now: 13 (41%) received radical surgical resection and 5 received concomitant chemo-radiotherapy. Three explorative laparotomy showed occult metastases. In other 7 cases surgery is planned while 2 patients refused surgery. Median progression-free survival is 14.0 months and median overall survival is 24.2 months with a two-year survival rate of 54%. Conclusions: Chemotherapy with FOLFOXIRI seems active in locally advanced PC and may allow to obtain a downstaging of disease leading to achieve a curative surgical resection in some cases. Longer follow up is needed to better evaluate long-term outcome of this strategy.

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