Effect of irreversible electroporation (IRE) combined with chemotherapy (C) on survival in locally advanced pancreatic cancer (LAPC) patients (pts).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15723-e15723
Author(s):  
Michalis Karamouzis ◽  
Dimitrios Oikonomou ◽  
Nikolaos Dimitrokallis ◽  
Demetris Papamichael ◽  
Pantelis Kountourakis ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Delayed Gastric Emptying ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Metallic Stent ◽  
Free Survival ◽  
Unacceptable Toxicity

e15723 Background: LAPC represents 40% of PC pts. IRE is a non-thermal ablative technique that can be used in inoperable pts and safely combined with C. Methods: From 2015 to 2018 laparotomic IRE was performed in a total of 34 LAPC pts. The median age was 64.7yrs (range, 46-81yrs) and 15 (44%) were males. The median tumor size was 3.9cm (range, 2-5.2cm) with the majority of tumors located at pancreatic head (26 pts, 76%), followed by body (6 pts, 18%) and tail of pancreas (2 pts, 6%). Induction C was applied in 27 out of 34 pts and in case of disease control IRE was done, while in 7 pts IRE was done without prior C. In the majority of pts C after IRE was also given. Results: Induction C was applied in 27 out to 34 pts (80%) [FOLFIRINOX in 16 pts, nab-paclitaxel-gemcitabine (AG) in 11 pts]. After the completion of 3 cycles of C tumor evaluation showed partial response (PR) in 20 pts and stable disease (SD) in 7 pts. All pts were treated with IRE and 50% of them had a preoperative biliary stent, while 3 pts had metallic stent that was removed before IRE. No IRE-related deaths occurred. Two major complications grade III were reported: pancreatic fistula grade A in 7 pts and 2 pts diagnosed with delayed gastric emptying. There was also one minor complication (wound infection) in 3 pts (9%). Up to 31/12/2018, the median overall survival (OS) of all pts was 24.2 months (mos) (range, 6-36 mos) and median progression free survival (PFS) was 14.6 mos (range, 3-24 mos). The median OS of the pts treated with C-IRE-C was 22.5 mos (range, 13-36 mos) and median PFS 16.9 mos (range, 3-24 mos), while in pts treated with IRE-C only was 15 mos (6-22 mos) and 10.9 mos (range, 5-16 mos), respectively. The group treated with FOLFIRINOX-IRE-C showed median OS 22.5 mos (range, 15-36 mos) and median PFS 17.1 mos (range, 3-24 mos), while the group treated with AG-IRE-C had median OS 19 mos (range, 13-36 mos) and median PFS 15.8 mos (range, 7-24 mos). After IRE, 24 pts (71%) continued with adjuvant C, either FOLFIRINOX 5 pts (15%) or G-based regimen 18 pts (46%) until disease progression or unacceptable toxicity, while 12 pts (35%) have more than 24 mos OS and 3 pts (9%) have reached 36 mos OS and are still alive. Conclusions: The combination of C with IRE is safe and results in survival increase of LAPC pts. Pts treated with the sequence FOLFIRINOX-IRE-C seems to benefit the most.

scholarly journals Irreversible electroporation for locally advanced pancreatic cancer

2018 ◽  
Vol 23 (2) ◽  
pp. 59-68
Author(s):  
D. A. Astakhov ◽  
D. N. Panchenkov ◽  
Yu. V. Ivanov ◽  
O. R. Shablovsky ◽  
A. G. Kedrova ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Head ◽  
Locally Advanced Pancreatic Cancer ◽  
Control Group ◽  
Recurrence Free Survival ◽  
Free Survival

Aim. To assess overall survival and recurrence-free period in patients with locally advanced pancreatic cancer who underwent irreversible electroporation of the tumor in combination with chemotherapy. Matherials and methods. It was performed a prospective analysis of overall survival in 23 patients who underwent irreversible electroporation of unresectable pancreatic cancer for the period from May 2012 to March 2017. Control group consisted of 35 patients with pancreatic cancer stage III who received standard chemotherapy alone. Results. Mean age of patients was 61 years (range 45–80). All procedures were successful. Fifteen patients had pancreatic head cancer, 8 – cancer of pancreatic body. Preoperative chemotherapy has been applied in 20 (86.9%) patients for 4 months prior to surgery on the average. Seventeen (73%) patients underwent chemotherapy after electroporation procedure. 90-day mortality was 4.3% (n = 1) in electroporation group. Surgery was followed by improved local recurrence-free survival (12 and 6 months, respectively, p = 0.01) and distant recurrence-free survival (15 and 8 months, respectively, p = 0.03). Overall survival was 18 and 11 months, respectively (p = 0.03). Conclusion. Irreversible electroporation of locally advanced pancreatic cancer is safe. Four-month chemotherapy followed by surgical procedure is associated with good local response and better overall survival compared with chemotherapy alone. These data will be validated in further multicenter study.

scholarly journals Effectiveness of Carbon Ion Radiation in Locally Advanced Pancreatic Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Jakob Liermann ◽  
Patrick Naumann ◽  
Fabian Weykamp ◽  
Philipp Hoegen ◽  
Juergen Debus ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Local Control ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Locally Advanced Pancreatic Cancer ◽  
Carbon Ion Radiotherapy ◽  
Free Survival ◽  
Carbon Ion

PurposeEffective treatment strategies for unresectable locally advanced pancreatic cancer (LAPC) patients are eagerly warranted. Recently, convincing oncological outcomes were demonstrated by carbon ion radiotherapy. Nevertheless, there is a lack of evidence for this modern radiation technique due to the limited number of carbon ion facilities worldwide. Here, we analyze feasibility and efficacy of carbon ion radiotherapy in the management of LAPC at Heidelberg Ion Beam Therapy Center (HIT).MethodsBetween 2015 and 2020, 21 LAPC patients were irradiated with carbon ions with a total dose of 48 Gy (RBE) in single doses of 4 Gy (RBE). Three patients (14%) were treated with concomitant chemotherapy with gemcitabine 300 mg/m2 body surface weekly. Toxicity rates were extracted from the charts. Overall survival, progression free survival, local control, and locoregional control were evaluated using Kaplan–Meier estimates.ResultsOne patient developed ascites CTCAE grade III during radiotherapy, which was related to a later histologically confirmed metachronous peritoneal carcinomatosis. No further higher-graded toxicity could be observed. The most common symptoms were nausea and abdominal pain. After a median estimated follow-up time of 19.1 months, the median progression free survival was 3.7 months, and the median overall survival was 11.9 months. The estimated 1-year local control and locoregional control rates were 89 and 84%, respectively.ConclusionCarbon ion radiotherapy of LAPC patients is safely feasible. Local tumor control rates were high. Nevertheless, compared to historical data, an overall survival improvement could not be observed. This could be explained by the poor prognosis of the selected underlying patients that mostly did not respond to prior chemotherapy as well as the early and frequent emergence of distant metastases that demonstrate the necessity of additional chemotherapy in further studies.

Effect of neoantigen reactive T cells combined with chemotherapy and radiation on survival in advanced pancreatic cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15756-e15756
Author(s):  
Qin Liu ◽  
Zhengyun Zou ◽  
Baorui Liu ◽  
Weiwei Kong ◽  
Fangjun Chen ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
T Cells ◽  
Cytotoxic T Lymphocyte ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Standard Regimen ◽  
Free Survival ◽  
Therapeutic Modalities ◽  
Lymphocyte Transfer

e15756 Background: Pancreatic cancer (PC) is one of the most aggressive and death-relating malignancy. Gemcitabine (GEM) is the key agent in the first-line standard regimen for advanced PC, which is mostly diagnosed at advanced stage and unsuitable for curative resection. The objective responsive rate (ORR) and medium progression free survival (PFS) of various GEM-based regimens are still unsatisfied. Therefore, development of new therapeutic modalities, including immunotherapy, is needed. This study is to investigate the efficacy, safety and clinical beneficial of combination neoantigen based immunotherapy with GEM and radiotherapy in locally advanced and metastatic PC patients. Methods: Three locally advanced unresectable and seven metastatic PC patients received at least two cycles of GEM (1000mg/m2 on day 1 and day 6), radiotherapy combing with neoantigen induced DC vaccination on day 7 and cytotoxic T lymphocyte transfer from day 12 to 15 (repeated every 21 days). The locally advanced unresectable PC patients received stereotactic body radiotherapy (SBRT) with a total amount of 50-66Gy during the first cycle. For metastatic patients, their partial lesions received a low dose radiation (0.5Gy bid*2days ) on day 10 and 11 in each cycle. Results: Two cases were observed with partial remission (PR), five with stable disease (sd), and three with progressive disease (PD). The disease control rate (DCR) was 70%. Median progression free survival (PFS) was 6.4 months. After the first treatment cycle, the total effectiveness for pain easement and increasing appetite are 100% (8/8)and 66.7%, respectively. Haematotoxicities with a 40% incidence rate were the most common adverse drug reactions. Two patients had grade 1 to 2 neutropenia, two with grade 3 to 4 thrombocytopenia. Three patients suffered grade 1 to 2 gemcitabine-induced skin rash. No treatment-related mortality occurred. Conclusions: Neoantigen reactive T cells combined chemoradiotherapy demonstrated an acceptable response and safety in advanced pancreatic cancer patients.

scholarly journals The Impact of Thromboprophylaxis on the Survival of Patients with Advanced Pancreatic Cancer. The Pancreatic Cancer and Tinzaparin (PaCT) Study

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2884
Author(s):  
Michalis V. Karamouzis ◽  
Ilias Athanasiadis ◽  
Georgios Samelis ◽  
Christos Vallilas ◽  
Alexandros Bokas ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Published Data ◽  
Bleeding Events ◽  
Free Survival ◽  
Treatment Dose ◽  
The Impact

Pancreatic cancer (PaC) induces a prothrombotic and hypercoagulable state. The aim of this study was to investigate the effect of tinzaparin in combination with chemotherapy. The PaCT (pancreatic cancer and tinzaparin) study was a retrospective observational study that collected data regarding progression free survival (PFS) in advanced or metastatic PaC patients who received thromboprophylaxis with tinzaparin during chemotherapy with nab-paclitaxel (N) and gemcitabine (G). The primary end point was to compare, from already published data, the PFS of patients receiving thromboprophylaxis with tinzaparin with the PFS of patients receiving chemotherapy with N–G but no thromboprophylaxis. Secondary end points were efficacy and safety of anticoagulation. In total, 110 PaC patients, 93% with advanced or metastatic disease, treated with N–G and tinzaparin (10,291 ± 1176 Anti-Xa IU, OD, median duration 8.7, IQR: 5.6–11.9 months) were enrolled. Of these, 52% were males and; the median age was 68 (40–86 years). The tumor was located to in the pancreatic head at in 45% of the patients. The median PFS was 7.9 months (IQR: 5.0–11.8 months). Out of 14 similar studies (involving 2994 patients) identified via systematic search, it was determined that the weighted PFS of patients receiving N–G but no anticoagulation was 5.6 months. Therefore, patients receiving tinzaparin had 39.54% higher PFS than patients without thromboprophylaxis (p < 0.05). During the follow-up period of 18.3 ± 11.7 months, three (2.7%) thrombotic events were recorded while two clinically relevant non-major bleeding events occurred (1.9%). In conclusion, PFS in advanced PaC patients undergoing chemotherapy is positively impacted by anticoagulation. Thromboprophylaxis with tinzaparin in treatment dose is efficient and safe.

Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

2006 ◽  
Vol 24 (24) ◽  
pp. 3946-3952 ◽  
Author(s):  
Volker Heinemann ◽  
Detlef Quietzsch ◽  
Frank Gieseler ◽  
Michael Gonnermann ◽  
Herbert Schönekäs ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Median Overall Survival ◽  
Statistical Significance ◽  
Single Agent ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Hematologic Toxicity ◽  
Free Survival

Purpose To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. Patients and Methods Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. Results One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. Conclusion These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

The PACT trial: Interim results of a randomized trial of TNFerade biologic plus chemoradiation (CRT) compared to CRT alone in locally advanced pancreatic cancer (LAPC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4102-4102 ◽  
Author(s):  
N. Senzer ◽  
A. Rosemurgy ◽  
M. Javle ◽  
T. Reid ◽  
M. C. Posner ◽  
...  
Keyword(s):  
Tumor Response ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Inducible Promoter ◽  
Intratumoral Injection ◽  
Free Survival ◽  
Stage 4 ◽  
Tnf Α ◽  
Significant Difference

4102 Background: TNFerade is a second-generation replication-deficient adenovector, carrying the transgene encoding human TNF-α, regulated by the stress-inducible promoter Egr-1. In a phase I trial of TNFerade + radiation in 36 patients with advanced or refractory solid tumors, a 47% objective tumor response rate was observed, including 100% complete responses in 3 stage 4 melanoma patients, with 2/3 disease-free at >3.5 years. Methods: This controlled phase II trial randomizes 74 patients with newly diagnosed unresectable LAPC to 5-wks of TNFerade (4 × 1011 pu via weekly intratumoral injection) + CRT (5-FU [200 mg/m2/day CIV × 5 days/wk] and 50.4 Gy radiation) or CRT alone. All patients receive maintenance gemcitabine. Endpoints: Progression-free survival, safety, radiographic tumor response, CA 19–9 and survival. Results: In dose escalation (n=50) dose-limiting toxicities occurred in 3 patients at 1 × 1012 pu (pancreatitis in 2 and biliary obstruction), setting the MTD at 4 × 1011 pu. Compared with the first two cohorts (n=30), the MTD (n = 11) was associated with greater locoregional control and progression-free survival, a higher rate of stable or decreasing CA 19–9, improved overall survival (median = 11.2), and a high (45%) resection rate. Accrual continues in the randomized phase of the study at 20+ centers. The most frequent adverse events in the first 16 enrolled patients have been nausea (75%), abdominal pain (63%), constipation (50%), anemia (38%), diarrhea (38%), vomiting (38%), and weight loss (38%), with no significant difference in severity or frequency between the TNFerade + CRT and CRT groups. No thromboembolic events have been reported. Serum TNF-alpha levels have remained low (peak = 45.3 pg/mL, in a CRT patient). CA 19–9 has been stable (no change > 100 U/mL) or decreased in all but one CRT patient. Conclusions: These initial data indicate that TNFerade plus CRT, given as weekly intratumoral injections to patients with LAPC, is feasible and tolerable compared to CRT alone. With continued accrual, comparative tumor response and toxicity data will be available and updated. No significant financial relationships to disclose.

Intensity-modulated radiation therapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC).

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 377-377 ◽  
Author(s):  
Carla Hajj ◽  
Florence Huguet ◽  
Abraham Jing-Ching Wu ◽  
Eileen Mary O'Reilly ◽  
Corinne Winston ◽  
...  
Keyword(s):  
Local Control ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Positive Margin ◽  
Surgical Patients ◽  
Hematologic Toxicity ◽  
Free Survival ◽  
Local Progression

377 Background: To assess IMRT safety and evaluate local control and resectability among patients with LAPC treated with induction CT followed by IMRT. Methods: We reviewed records of 134 LAPC patients treated with CT (median duration 3.2 months) followed by IMRT (median dose 56 Gy) between 11/2006 and 11/2012. Patients had LAPC based on T4 disease or unreconstructable involvement of portal vein/hepatic artery on imaging (n=102) or were found to be unresectable after an attempted resection (n=32). Induction CT was gemcitabine-based (n=98) or FOLFIRINOX (n=32); concurrent CT was gemcitabine in 88 patients, continuous 5-FU or capecitabine in 37 patients. IMRT was given after induction CT in the absence of evidence of disease progression. After IMRT, 81 patients received maintenance CT. Results: Acute grade 3 GI and hematologic toxicity were seen in 4 (2.9%) and 33 (24.6%) patients, respectively. Acute grade 4 GI and hematologic toxicity were seen in 0 and 5 (3.7%) patients, respectively. Ten patients (7.4%) developed late grade 1 GI toxicity and 2 patients (0.7%) developed compression fractures. Twenty-six (19.4%) patients underwent resection 4.1 months (mean) after IMRT; 22 (84.6%) had negative margins, one of whom had a pathologic complete response and 4 had a microscopically positive margin. With 20.1 months median f-up, median local progression-free survival (LPFS) was 17.6 months. One- and 2-year LPFS were 90% and 55% respectively. Median distant metastasis free survival (DMFS) was 15.2 months. One- and 2-year DMFS were 69.5% and 30.7% respectively. Median OS was 19.7 months for the whole population (24.8 months for surgical patients and 19.7 months for the non-surgical patients). One- and 2-year OS for all patients were 85% and 47% respectively; one- and 2-year OS for the surgical patients were 96% and 72% respectively. Conclusions: In this large cohort of patients treated with IMRT for LAPC, acute and late toxicity was minimal. Patients with non-progressive LAPC after induction CT who received IMRT had high rates of local control which could translate into a better quality of life. In selected patients, induction CT followed by IMRT can downstage tumors allowing for R0 resections and improved overall survival.

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