scholarly journals Complete Responses after Hyperthermic Ablation by Ultrasound Guided High Intensity Focused Ultrasound Plus Systemic Chemotherapy for Locally Advanced Pancreatic Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Joan Vidal-Jove ◽  
Marta Garcia-Bernal ◽  
Eloi Perich ◽  
Manuel Alvarez del Castillo
Keyword(s):  
Pancreatic Cancer ◽  
Systemic Chemotherapy ◽  
Combined Treatment ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
High Intensity Focused Ultrasound ◽  
Stage Iii ◽  
Pancreatic Tumors ◽  
Clinical Responses

We describe results in unresectable pancreatic tumors treated with USgHIFU hyperthermia ablation plus adjuvant chemotherapy. Materials and Methods. Thirty two cases of nonresectable pancreatic tumors were treated from March 2010 to March 2012, and all of them underwent systemic chemotherapy. Clinical responses (thermal ablation achieved) were measured by image techniques. There were 23 stage III cases and 9 stage IV cases. Complications were also analyzed. Results. Clinical responses (ablation obtained) were 82% in all cases, sustained at 8 weeks of the procedure. We obtained 8 complete responses (25%) at the end of the combined treatment, 7 from stage III patients and 1 from stage IV. Major complications included (1) severe pancreatitis with GI bleeding and (2) skin burning grade III that required plastic surgery. No deaths were registered. Median survival was 12.5 month (6 months–2.5 year). Conclusion. HIFU plus SC is a potentially effective and safe modality for the treatment of unresectable pancreatic cancer.

scholarly journals Intraoperative HIFU Ablation of the Pancreas Using a Toroidal Transducer in a Porcine Model. The First Step towards a Clinical Treatment of Locally Advanced Pancreatic Cancer

Cancers ◽  
2021 ◽  
Vol 13 (24) ◽  
pp. 6381
Author(s):  
Celia Cilleros ◽  
Aurélien Dupré ◽  
Yao Chen ◽  
Jeremy Vincenot ◽  
Michel Rivoire ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
High Intensity Focused Ultrasound ◽  
Locally Advanced Pancreatic Cancer ◽  
Pancreatic Tumors ◽  
Great Promise ◽  
Ultrasound Images ◽  
Mesenteric Vessels

Apart from palliative chemotherapy, no other therapy has been proven effective for the treatment of locally advanced pancreatic tumors. In this study, an intraoperative high-intensity focused ultrasound (HIFU) device was tested in vivo to demonstrate the feasibility of treating the pancreatic parenchyma and tissues surrounding the superior mesenteric vessels prior to clinical translation of this technique. Twenty pigs were included and treated using a HIFU device equipped with a toroidal transducer and an integrated ultrasound imaging probe. Treatments were performed with energy escalation (from 30 kJ to 52 kJ). All treatments resulted in visible (macroscopically and in ultrasound images) homogeneous thermal damage, which was confirmed by histology. The dimensions of thermal lesions measured in ultrasound images and those measured macroscopically were correlated (r = 0.82, p < 0.05). No arterial spasms or occlusion were observed at the lowest energy setting. Temporary spasm of the peripancreatic artery was observed when using an energy setting greater than 30 kJ. The possibility of treating the pancreas and tissues around mesenteric vessels without vascular thrombosis holds great promise for the treatment of locally advanced pancreatic cancers. If clinically successful, chemotherapy followed by HIFU treatment could rapidly become a novel treatment option for locally advanced pancreatic cancer.

Safety and tolerability of combined gemcitabine (G) and erlotinib (E) plus sorafenib (S) in the first-line treatment of metastatic pancreatic cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15594-e15594 ◽  
Author(s):  
D. J. Cohen ◽  
T. Ryan ◽  
T. Moskovits ◽  
N. Cazeau ◽  
E. Newman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Kinase Inhibitor ◽  
Bowel Perforation ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Median Number ◽  
Metastatic Pancreatic Cancer ◽  
Pancreatic Tumors ◽  
Disease Stabilization ◽  
Ecog Ps

e15594 Background: The addition of E to G results in improved survival for patients(pts) with locally advanced and metastatic pancreatic cancer. Many pancreatic tumors have constitutively activated ras/raf pathways and overexpress VEGF. Sorafenib, a multitargeted tyrosine kinase inhibitor which targets VEGR 1–3, PDGFR-α and β and the RAF/MEK/ERK pathway, when combined with G and E may synergize with these agents resulting in a more complete blockade of the signal transduction cascade in pancreatic cancer growth and progression and therefore improve outcome. Methods: Pts with previously untreated, histologically confirmed, unresectable pancreatic adenocarcinoma, ECOG PS 0–1, and adequate organ function were eligible and received G 1,000 mg/m2 over 30 min weekly × 3 every 4 weeks. E 150 mg PO daily and S 400 mg PO bid were given continuously. CT scans were performed every 2 cycles (8 weeks). Endpoints included safety and tolerability of the novel combination, PFS at 4 months, response rate, and OS. Results: Between 9/07–12/08 19 pts were enrolled with a median age 59 (range 45- 75), M/F 13/6, PS (0/1) 14/5. All 19 had metastatic disease. 17 pts are evaluable for toxicity and efficacy. The median number of cycles on treatment was 2 (range 1–10). The most common grade (gr) 3 toxicities were thrombocytopenia (24%), venous thrombosis (12%), and hyperbilirubinemia (12%). The most common gr 4 toxicity was infection (12%). 1 pt each experienced gr 3 HFSR, gr 3 diarrhea, gr 3 bleeding (epistaxis) and 1 had a non-fatal bowel perforation. There was 1 PR and 6 SD for an overall RR of 6% and a DCR of 41%. Conclusions: The combination of G and E plus S in the treatment of advanced pancreatic cancer is a well tolerated regimen without significant increased toxicity as compared to gemcitabine alone, except for very manageable cutaneous reactions. Further follow up is required to determine the combination's efficacy, though some patients have achieved prolonged disease stabilization. Supported in part by grants from Bayer Healthcare Pharmaceuticals/Onyx and OSI. [Table: see text]

Phase I trial of gene-mediated cytotoxic immunotherapy in combination with chemoradiation for locally advanced pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 195-195 ◽  
Author(s):  
M. Bloomston ◽  
C. Marsh ◽  
J. Walker ◽  
W. Coyle ◽  
H. Marx ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Median Survival ◽  
Tumor Vaccine ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Pancreatic Tumors ◽  
Kinase Gene ◽  
Early Results ◽  
Cell Immunity ◽  
Dose Levels

195 Background: More than 80% of patients with pancreatic cancer present with locally advanced or metastatic disease and have a median survival of only 6 months. Immunotherapy approaches may improve outcomes. Gene Mediated Cytotoxic Immunotherapy (GMCI) is an approach that generates a systemic anti-tumor vaccine effect through intra-tumoral delivery of an adenoviral vector expressing the HSV-thymidine kinase gene (AdV-tk) followed by anti-herpetic prodrug and synergy with chemoradiation. The mechanisms of action involve tumor cytotoxicity, activation of antigen presenting cells and stimulation of systemic anti-tumor T-cell immunity. Safety with potential efficacy has been demonstrated in multiple clinical studies. This is the first application of GMCI in pancreatic cancer. Methods: This study evaluated 4 dose levels of AdV-tk (3x1010 to 1x1012 vector particles) injected into locally advanced tumors via EUS or CT-guidance before and during week 3 of standard 5-FU-chemoradiation. Valacyclovir (Valtrex, GSK) prodrug was given for 14 days after each of 2 AdV-tk injections. Results: The study completed accrual with 13 patients enrolled and 12 completing therapy with 3 at each of the 4 dose levels. One patient refused further participation during course 1 after recovering from azotemia. Median age was 64 years (range 55-81) and median baseline CA19-9 was 1634 U/ml. No dose limiting toxicities and no injection related complications occurred. Possibly related grade 3-4 toxicities, all of which were transient, included dehydration, azotemia and worsening elevation of bilirubin and AST. Kaplan-Meier estimated median survival is 12.2 months with 6 patients still alive at 8-20 months. Two patients achieved a partial response by RECIST criteria. One occurred in week 6 despite discontinuing 5-FU/radiation during week 1. The other had gradual decrease of a 7 cm tumor over 11 months. Serum CA19-9 levels decreased in 8/8 evaluable patients by 32-91% at 3 months after treatment initiation. Conclusions: AdV-tk can be safely injected into pancreatic tumors and combined with standard chemoradiation. Early results are highly encouraging and justify further evaluation in a phase II study. [Table: see text]

Outcome analysis of chemotherapy duration for resected stage I-II and unresected stage III pancreatic cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 375-375
Author(s):  
Sung Jun Ma ◽  
Austin J Iovoli ◽  
Kavitha M Prezzano ◽  
Gregory Hermann ◽  
Lucas M Serra ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Propensity Score ◽  
Propensity Score Matching ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Advanced Pancreatic Cancer ◽  
Stage I ◽  
Stage Iii ◽  
Outcome Analysis ◽  
Resected Stage

375 Background: For resected early-stage pancreatic cancer, RTOG 9704 has evaluated the outcome of 3 weeks of adjuvant chemotherapy (C) followed by chemoradiation (CRT) and post-CRT C. For locally advanced pancreatic cancer, a recent literature review showed that the typical duration for induction C is between 1 and 6 months prior to CRT. The ideal duration of C prior to CRT remains unclear. This National Cancer Database (NCDB) study was performed to identify the optimal duration of C prior to CRT in patients with pancreatic cancer. Methods: The NCDB was queried for primary stage I-II, cT1-3N0-1M0, resected and stage III, cT4N0-1M0, unresected pancreatic adenocarcinoma treated with C+CRT (2004-2015). Cohorts I-II and III included stage I-II and stage III cases, respectively. In each cohort, the patients were stratified by the short (short C) and long duration (long C) of chemotherapy based on their median durations (70 and 90 days between the onset of chemotherapy and radiation for cohorts I-II and III, respectively). Baseline patient, tumor, and treatment characteristics were examined. The primary endpoint was overall survival (OS). Kaplan-Meier analysis, multivariable Cox proportional hazards method, and propensity score matching were used. Results: Among 1,577 patients, cohort I-II had 839 patients (n = 409 with short C, n = 430 with long C) and cohort III had 738 patients (n = 360 with short C, n = 378 with long C). Median follow-up was 39.5 months and 24.3 months for cohorts I-II and III, respectively. The long C group showed improved OS in the multivariable analysis in both cohort I-II (HR 0.72, p < 0.001) and cohort III (HR 0.83, p = 0.025). Using 1:1 propensity score matching, a total of 610 patients for cohort I-II and 542 patients for cohort III were matched. After matching, long C remained statistically significant for improved OS compared with short C in both cohort I-II (median OS 26.1 vs 21.9 months, p = 0.003) and cohort III (median OS 16.7 vs 14.2 months, p = 0.021). Conclusions: Our NCDB study using propensity score matched analysis showed a survival benefit in the use of longer duration chemotherapy compared to shorter duration chemotherapy for both resected stage I-II and unresected stage III pancreatic cancer.

scholarly journals Retrospective Clinical Study of Advanced Pancreatic Cancer Treated With Chemotherapy and Abdominal Hyperthermia

2018 ◽  
pp. 1-4 ◽  
Author(s):  
Yu-Fei Fan ◽  
Yuan Qin ◽  
Ding-Gang Li ◽  
David Kerr
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Treatment Modalities ◽  
Hyperthermia Treatment ◽  
Regional Hyperthermia ◽  
Retrospective Clinical Study ◽  
Clinical Series

Purpose Hyperthermia is a mechanistically plausible partner with chemotherapy, although many of the underlying molecular mechanisms of this combination treatment are not yet properly understood. Preclinical studies suggest that there is potential synergy with gemcitabine and that provides the basis for retrospective analysis of a clinical series combining these treatment modalities for patients with advanced pancreatic cancer. Patients and Methods Twenty-nine chemotherapy-naive patients with locally advanced or metastatic pancreatic carcinoma with malignant ascites were treated with intraperitoneal cisplatin 30 mg/m2 and gemcitabine 800 to 1,000 mg/m2 intravenously on days 1, 8, and 15 every 28 days until tumor progression. Patients also received regional hyperthermia treatment (41 to 42°C) on the upper abdomen two times per week from days 1 to 21. Results In all, 83 cycles of chemotherapy were administered and were generally well tolerated. No patients had a complete response, 13 had a partial response, seven had stable disease, and 9 had progressive disease. Mean progression-free survival and overall survival were 119 ± 61days and 195 ± 98 days, respectively. Conclusion This study provides preliminary evidence that the treatment approach of combined systemic and intraperitoneal chemotherapy plus hyperthermia is well tolerated, is active, and has an acceptable survival profile for patients with stage IV pancreatic cancer and ascites.

18F-fluorothymidine (FLT) PET-CT for early response assessment in advanced pancreatic cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21093-e21093
Author(s):  
Amarnath Challapalli ◽  
Harpreet S Wasan ◽  
Adil Al-Nahhas ◽  
Eric Aboagye ◽  
Charles Coombes ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Locally Advanced ◽  
Advanced Pancreatic Cancer ◽  
Standardized Uptake Value ◽  
Response To Therapy ◽  
Pancreatic Tumors ◽  
Metastatic Tumors ◽  
Flt Pet ◽  
Pet Ct ◽  
The Mean

e21093 Background: Advanced pancreatic cancer has a poor prognosis with a median survival of 6-10 months. There is a need for early non-invasive assessment of treatment response. We evaluated FLT PET-CT combined with a kinetic spatial filtering method (FLT-PETKSF) for detecting response to gemcitabine-based chemotherapy in advanced pancreatic cancer. Methods: Dynamic FLT PET-CT data were collected from patients with confirmed locally advanced or metastatic pancreatic cancer before and 2 weeks after the first cycle of chemotherapy. Changes in tumor FLT-PET variables with treatment were determined. Standardized uptake value (SUV) reduction of 18% was taken as cut-off for response. Voxel quantification of each tumor volume was performed on the filtered data. Each voxel-intensity was normalised by injected dose, body weight and decay corrected to obtain the SUV for the voxel. Changes in high intensity voxels (HiVox: SUV ≥ 2) - were computed. Results: Results of the first 5 patients are discussed. There were 4 primary and 9 metastatic tumors. FLT-PETKSF improved tumor-to-background ratio and enabled visualisation of all the primary and metastatic tumors. The mean (± SD) average and maximum SUV at 60 min (SUV60, av & SUV60, max) of the primary lesions was 2.10 (±0.38) & 4.85 (±1.55) and that of the metastatic lesions was 3.74 (±1.49) & 6.90 (±2.05) respectively. The mean (± SD) percentage reduction in the SUV60, av & SUV60, max, HIVox was 26 (±44), 18 (±38) and 23 (±50) respectively. The changes in the voxel occurrences correlated strongly with the changes in both SUV60, av & SUV60, max (Pearson r-0.9, p=0.001) .Overall, there were 2 partial responders and 3 with stable disease. These responses concurred with response evaluation on mid-treatment CT scan. Conclusions: FLT-PET and FLT-PETKSF enables visualisation of the pancreatic tumors and the liver metastases, and could be used to monitor response to therapy.

Trends in treatment and survival for advanced pancreatic cancer: Progress or progression?

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 421-421
Author(s):  
Mariam F. Eskander ◽  
Gyulnara G. Kasumova ◽  
Chun Li ◽  
Sing Chau Ng ◽  
Rebecca A. Miksad ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Clinical Stage ◽  
Advanced Pancreatic Cancer ◽  
Stage Iv ◽  
Tumor Location ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Cox Proportional Hazards Models

421 Background: There are increasing therapeutic options for patients with advanced pancreatic cancer but it is unknown whether the overall prognosis of unresectable patients is improving. Here, we examine trends in treatment and survival in Stage III/IV pancreatic cancer. Methods: National Cancer DataBase 1998-2012 queried for unresected pancreatic adenocarcinoma patients from Commission on Cancer hospitals with Stage III and IV disease. Trends in stage at diagnosis and type of chemotherapy (single vs. multi-agent) assessed via Cochran Armitage trend tests. Timing of treatment compared by Kruskal-Wallis. Kaplan-Meier analysis and Cox proportional hazards models used to assess the association between 2-year time intervals (1998-2011) and survival. Results: 34,163 unresected patients with Stage III and 100,396 with stage IV identified. Rates of chemotherapy increased over time for stage III (p<0.0001) and stage IV (p<0.0001). Among patients who received systemic therapy, rates of multiagent chemotherapy have increased for both stage III (p<0.0001) and IV (p<0.0001). Time from diagnosis to treatment did not change (p=0.5121). Overall survival differed by year group for stage III (5.2 mos in 1998-1999 vs. 9.0 mos 2010-2011, log-rank p<0.0001) and stage IV (3.1 vs. 3.6 mos; log-rank p<0.0001). Among patients who received chemotherapy, overall survival also differed (Stage III, 7.6 vs. 11.4 mos, log-rank p<0.0001; Stage IV, 5.0 vs. 6.0 mos, log-rank p<0.0001). After stratification by clinical stage, type of chemotherapy, tumor location, and facility type, year remained a significant predictor of survival (p<0.0001). Conclusions: Survival of patients with Stage III and IV pancreatic cancer has significantly improved over the last fifteen years. This improvement in survival is not fully explained by changes in chemotherapy. [Table: see text]

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