Irresectable Pancreatic Cancer Research Articles

Second-line and third-line therapy with nanoliposomal irinotecan (nal-IRI) in pancreatic cancer: a single-center experience and review of literature.

Prognosis of patients with pancreatic cancer is still extremely poor. First-line palliative therapies with FOLFIRINOX or gemcitabine/nab-paclitaxel have been established in the last decade. In the second-line, 5-FU/LV in combination with nanoliposomal irinotecan (nal-IRI) after gemcitabine has been shown to be effective. However, the use of nal-IRI as third-line therapy after FOLFIRINOX and gemcitabine-based chemotherapies is still controversial. In this study, we report about the use of 5-FU/LV + nal-IRI in a daily practice and analyze whether nal-IRI is an option as third-line therapy after FOLFIRINOX and gemcitabine/nab-paclitaxel. This is a single center retrospective analysis of patients with irresectable pancreatic cancer who were treated with 5-FU/LV and nal-IRI from 2017 to 2021 as second- or third-line palliative treatment. Overall survival (OS), progression-free survival (PFS) and toxicity were analyzed, and multivariate analysis was used to identify independent prognostic factors. Twenty-nine patients receiving 5-FU/LV and nal-IRI were included in the analysis. The majority of patients (n=19) received 5-FU/nal-IRI as third-line therapy after pre-exposition to FOLFIRINOX and gemcitabine/nab-paclitaxel. Median OS and PFS were 9.33 months (95% CI: 3.37, 15.30) and 2.90 months (95% CI: 1.64, 4.16), respectively. Furthermore, patients receiving nal-IRI + 5-FU/LV as third-line treatment also showed some benefits, with no OS difference compared to second-line patients (9.33 vs. 10.27 months; HR: 1.85; 95% CI: 0.64, 5.41; P=0.253). Adverse effects were similar to reported trials. In our study, the use of 5-FU/nal-IRI in unselected patients with advanced pancreatic cancer showed similar OS, PFS and tolerance as randomized prospective phase II/III trials. Interestingly, the use of 5-FU/nal-IRI seemed to be beneficial in third-line therapy, despite a pre-exposure to non-liposomal irinotecan.

Sequence Therapy with FOLFIRINOX and Gemcitabine/Nab-Paclitaxel for Patients with Advanced Pancreatic Cancer: A Monocentre Retrospective Cohort Study

Background and Aims: While irresectable pancreatic cancer has still a dismal overall prognosis, evidence about the optimal chemotherapy sequence is scarce. After treatment with FOLFIRINOX in first-line, gemcitabine monotherapy was established for years. As a potential treatment alternative after failure of FOLFIRINOX therapy, combination of gemcitabine and nab-paclitaxel is used. However, this combination has formally not yet been approved for second-line treatment and investigation of efficiency and treatment tolerance is the aim of this trial. Methods: Therefore, we investigated 225 patients with histologically confirmed local advanced or metastatic pancreatic cancer in this retrospective monocentre study (November 2010 – July 2019). Of this, 44 patients received FOLFIRINOX therapy and outcome was further analysed. The primary end point of this cohort was overall survival (OS), and secondary end points included progression-free survival (PFS), response rate, and safety. Results: In most of the patients, FOLFIRINOX as first-line treatment of irresectable pancreatic cancer resulted in temporary cancer control (partial response [PR]: 50% and stable disease [SD]: 18%), whereas tumour progression was observed in 23% of the patients. The median PFS time for FOLFIRINOX treatment was 7.3 months and median OS 10.3 months. Seven (16%) patients received additional local radio chemotherapy of the pancreatic tumour. During first-line therapy, in 8 (18%) patients, laparotomy was performed to proof resectability of the tumour. Hereby, in 3 patients R0- and in 3 patients R1 resection was achieved, whereas 2 patients stayed irresectable. Twenty-five of the 44 patients (57%) received second-line therapy, namely, 24 patients gemcitabine/nab-paclitaxel and 1 patient gemcitabine and erlotinib. Hereby, gemcitabine/nab-paclitaxel led again to temporary tumour control in 46% of the patients (PR: 21%, SD: 25%), while in 29% of the patients, disease progression was observed. Corresponding median PFS for gemcitabine and nab-paclitaxel treatment was 3.5 months. Patients who received second-line treatment with nab-paclitaxel and gemcitabine had a more favourable prognosis (median OS: 17 vs. 9.2 months; HR 0.32 [0.14–0.70], p < 0.001) than patients who were not eligible for second-line treatment. Moreover, in multivariate analyses association with patients’ survival and tumour response to chemotherapy in both therapeutic lines and µGT concentrations below 100 IU/L in first-line FOLFIRINOX chemotherapy were observed. Conclusion: These real-world data suggest that gemcitabine/nab-paclitaxel may be feasible after FOLFIRINOX therapy in patients with irresectable pancreatic cancer. However, prospective randomized data about the superiority to gemcitabine monotherapy are needed.

Safety of radiofrequency ablation in patients with locally irresectable pancreatic cancer

Safety of radiofrequency ablation in patients with locally irresectable pancreatic cancer

Neoadjuvant radiotherapeutic strategies in pancreatic cancer.

This review summarizes the current status of neoadjuvant radiation approaches in the treatment of pancreatic cancer, including a description of modern radiation techniques, and an overview on the literature regarding neoadjuvant radio- or radiochemotherapeutic strategies both for resectable and irresectable pancreatic cancer. Neoadjuvant chemoradiation for locally-advanced, primarily non- or borderline resectable pancreas cancer results in secondary resectability in a substantial proportion of patients with consecutively markedly improved overall prognosis and should be considered as possible alternative in pretreatment multidisciplinary evaluations. In resectable pancreatic cancer, outstanding results in terms of response, local control and overall survival have been observed with neoadjuvant radio- or radiochemotherapy in several phase I/II trials, which justify further evaluation of this strategy. Further investigation of neoadjuvant chemoradiation strategies should be performed preferentially in randomized trials in order to improve comparability of the current results with other treatment modalities. This should include the evaluation of optimal sequencing with newer and more potent systemic induction therapy approaches. Advances in patient selection based on new molecular markers might be of crucial interest in this context. Finally modern external beam radiation techniques (intensity-modulated radiation therapy, image-guided radiation therapy and stereotactic body radiation therapy), new radiation qualities (protons, heavy ions) or combinations with alternative boosting techniques widen the therapeutic window and contribute to the reduction of toxicity.

Thoracoscopic Splanchnicectomy for Pain Control in Irresectable Pancreatic Cancer

Disabling pain for many patients with irresectable pancreatic cancer is poorly managed and can remain a significant problem until death. The aim of this study was to evaluate the safety and efficacy of thoracoscopic splanchnicectomy for pain control in patients with irresectable pancreatic cancer. Thirteen patients suffering from intractable pain due to irresectable pancreatic cancer underwent 15 attempted thoracoscopic splanchnicectomy procedures. All patients were opiate dependent. Right-sided splanchnicectomy was performed for a dominantly right-sided pain, whereas a centralized, bilateral, or left-sided pain was managed by left splanchnicectomy. If pain recurred, patients were offered to have the procedure repeated on the contralateral side. Thoracoscopic splanchnicectomy procedure was a technical failure because of pleural adhesions in 1 patient. Fourteen (10 left- and 4 right-sided) thoracoscopic splanchnicectomies were successfully completed in 12 patients. Immediate pain relief was achieved in all 12 patients after unilateral thoracoscopic splanchnicectomy. Pain relief persisted until death in 8 patients and until the latest postoperative follow-up visit at 5 months in 1 patient. Two patients required a contralateral procedure for pain recurrence. A 3rd patient had a recurrent pain but refused contralateral intervention. Except for the latter, none of the patients required opioids. Thoracoscopic splanchnicectomy is a safe, simple, and effective minimally invasive procedure. It offers a substantial relief of pain in patients with unresectable pancreatic cancer.

Venous thromboembolism predicts poor prognosis in irresectable pancreatic cancer patients

The aim was to investigate the outcomes associated with venous thromboembolism (VTE) among irresectable pancreatic cancer patients. This is a follow-up study of consecutive irresectable cancer patients, treated and followed up in clinical trials between December 2001 and December 2004 in order to evaluate the prognostic impact of symptomatic VTE on clinical outcomes, such as response to treatment, progression-free survival (PFS) and overall survival (OS). Among 227 irresectable pancreatic cancer patients, with Eastern Cooperative Oncology Group performance status (ECOG-PS) < or = 2, 59 (26.0%) patients developed a VTE. A synchronous VTE occurred in 28 (12.3%) patients, while a VTE during chemotherapy was observed in 15 (6.6%) patients, and 16 (7.0%) patients experienced both events. Presence of synchronous VTE was associated with a higher probability of not responding to treatment (odds ratio 2.98, 95% CI 1.42-6.27, P = 0.004), but showed no effect on both PFS and OS at least at multivariate analysis. Occurrence of a VTE during chemotherapy showed a statistically significant effect on PFS (hazard ratio [HR] 2.59, 95% CI 1.69-3.97, P < 0.0001) and OS (HR 1.64, 95%CI 1.04-2.58, P = 0.032). Our data suggest that the occurrence of VTE may be associated with a reduced response rate and a shorter PFS and OS among patients with irresectable pancreatic cancer. In these patients the development of VTE may reflect the presence of a biologically more aggressive cancer that in turn leads to a worse prognosis.

Use of Removable Covered Expandable Metal Stents (RCEMS) in the Treatment of Benign Distal Common Bile Duct (CBD) Strictures: A Feasibility Study

The endoscopic treatment of benign CBD strictures comprises of sequential plastic stent insertion in progressively increasing numbers and resolves 65-85% of post surgical strictures and 20-40% of strictures due to chronic pancreatitis (CP). We aimed to assess the feasibility of using RCEMS, especially its removability, in the treatment of benign CBD strictures. Methods: First, proof of principle was tested in 3 patients with irresectable pancreatic cancer (CA). Subsequently, 4 patients with CP with a benign distal CBD stricture were included.

A Continuing Role for Surgical Bypass in the Palliative Treatment of Pancreatic Carcinoma

Background: The use of palliative surgery for irresectable pancreatic cancer has been challenged by the advent of non-operative stenting, but it may still be appropriate for selected patients. Methods: Single-loop biliary and gastric bypass was carried out in 56 patients (mean age 60 years) with carcinomas of the pancreatic head that were irresectable because of vascular invasion or distant spread. In 42 patients without a preoperative tissue diagnosis, ductal carcinoma was confirmed by biopsy of the primary (n = 20) or secondary (n = 22) tumour. Preoperative biliary decompression in 31 patients led to positive bile cultures in 22 of 24 patients sampled. Results: There were no deaths in hospital or within 30 days. Complications in 20 patients (35%) included three biliary leaks, two of which required temporary percutaneous stents. The median postoperative hospital stay was 14 days. No re-operations were required before death, though 2 patients required percutaneous stenting of the biliary anastomosis for recurrent jaundice, 1 of whom had a radiation-induced stricture. The median survival was 6 (range 2–21) months. Conclusion: Combined biliary and gastric bypass can be carried out with reasonable safety and remains a useful option for patients with potentially resectable tumours and an anticipated life expectancy of at least 6 months.

Combined modality treatment with accelerated radiotherapy and chemotherapy in patients with locally advanced inoperable carcinoma of the pancreas: results of a feasibility study.

Between July 1990 and September 1993, 32 patients with locally advanced irresectable adenocarcinoma of the pancreas, histologically proven by laparotomy, were involved in our study. Patients were treated with hyperfractionated, accelerated radiotherapy and simultaneous application of 5-fluorouracil and folinic acid. Chemotherapy was given on days 1,2 and 3. Determination of the target volume for radiotherapy was carried out by computerized axial tomography. The total tumour dose of 44.8 Gy was applied relative to the 90% isodose in two daily fractions of 1.6 Gy, resulting in ten fractions per week. On the first three days of radiotherapy, 600 mg m-3 of 5-fluorouracil and 300 mg m-3 of folinic acid were given i.v. According to response, chemotherapy was repeated in 4-week intervals. The median survival time for all patients was 12.7 months, compared with 3-7 months after palliative surgery (historical control). The median progression-free interval was 6.6 months. Toxicity and therapy-induced morbidity were recorded according to WHO criteria. Nausea and vomiting of WHO grade I and II occurred in 72.1% and of grade III and IV in 27.9% of the patients. WHO grade I and II diarrhoea was seen in 11 patients. The overall incidence of leucopenia and thrombocytopenia was 37.4%; severe side-effects (WHO III-IV) occurred in 9.3% of all patients. One patient experienced a severe mucositis (WHO III). This combined modality treatment consisting of accelerated hyperfractionated radiotherapy and chemotherapy turned out to be feasible for patients with locally advanced, irresectable pancreatic cancer. The therapy could be applied in a short period of time, approximately half the time used in conventional therapy schemes.

Local therapy improves survival duration in pancreatic cancer

Compared with conventional systemic chemotherapy, locally delivered agents may prolong survival in patients with irresectable pancreatic cancer, according to Israeli investigators. The 5-year results of a study involving 54 patients with pancreatic cancer were presented at the 7th International Congress on Anti-Cancer Treatment [Paris, France; February 1997].