scholarly journals Surgery or Locoregional Approaches for Hepatic Oligometastatic Pancreatic Cancer: Myth, Hope, or Reality?

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1095 ◽  
Author(s):  
Michele Ghidini ◽  
Angelica Petrillo ◽  
Massimiliano Salati ◽  
Shelize Khakoo ◽  
Antonio Varricchio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Performance Status ◽  
Irreversible Electroporation ◽  
Multimodality Treatment ◽  
Ductal Adenocarcinoma ◽  
Surgical Approaches ◽  
Tumor Control ◽  
Recommended Treatment ◽  
Metastatic Setting

Despite extensive research, pancreatic ductal adenocarcinoma (PDAC) remains a difficult-to-treat cancer associated with poor survival. Due to the known aggressive disease biology, palliative chemotherapy is the only routinely recommended treatment in the metastatic setting in patients with adequate performance status. However, in a subset of patients with oligometastatic disease, multimodality treatment with surgery and/or locoregional approaches may provide long-term disease control and prolong survival. In fact, in highly selected cases, median overall survival has been reported to extend to 56 months in patients treated with surgery. In particular, liver and extraregional nodal resections may provide long-term tumor control with acceptable morbidity. Current guidelines do not recommend surgery for patients with metastatic PDAC and, in the case of PDAC with oligometastases, there are no published randomized controlled trials regarding locoregional or surgical approaches. Here we review the literature on surgical and locoregional approaches including radiofrequency ablation, irreversible electroporation, and stereotactic body radiation, and focus on patients with hepatic oligometastatic pancreatic cancer. We provide a summary regarding survival outcomes, morbidity and mortality and discuss selection criteria that may be useful to predict the best outcomes for such strategies.

scholarly journals Role of Stereotactic Body Radiotherapy in the Treatment of Elderly and Poor Performance Status Patients With Pancreatic Cancer

2017 ◽  
Vol 13 (3) ◽  
pp. 157-166 ◽  
Author(s):  
Lauren M. Rosati ◽  
Joseph M. Herman
Keyword(s):  
Pancreatic Cancer ◽  
Stereotactic Body Radiotherapy ◽  
Group Performance ◽  
Performance Status ◽  
Single Agent ◽  
Locally Advanced ◽  
Poor Performance ◽  
Tumor Control ◽  
Poor Performance Status ◽  
Patient Reported

Literature on the management of nonmetastatic pancreatic ductal adenocarcinoma in patients who are elderly or have poor performance status is sparse. The median survival of this unique cohort of patients is < 6 months, and most patients are only offered single-agent gemcitabine or supportive care. Recently, adding nanoparticle albumin-bound paclitaxel to gemcitabine was shown to improve survival of patients with metastatic disease with Eastern Cooperative Group performance status of 2. Although standard chemoradiotherapy provides long-term locoregional control in locally advanced pancreatic cancer, it is difficult for this group of patients to tolerate 6 weeks of therapy. Stereotactic body radiotherapy (SBRT) can be delivered in only 3 to 5 days, does not require concurrent chemotherapy, and has limited toxicity, and tumor control rates appear to be equivalent to or better than those achieved with standard chemoradiotherapy. Additionally, SBRT has been shown to improve cancer-related pain and patient-reported quality of life. Given the favorable toxicity profile, SBRT seems like an obvious choice for patients who are elderly, have multiple comorbidities, or have poor performance status. Herein, we review the literature on SBRT in this unique patient population and discuss future directions.

ESPAC-4: A multicenter, international, open-label randomized controlled phase III trial of adjuvant combination chemotherapy of gemcitabine (GEM) and capecitabine (CAP) versus monotherapy gemcitabine in patients with resected pancreatic ductal adenocarcinoma.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA4006-LBA4006 ◽  
Author(s):  
John P. Neoptolemos ◽  
Dan Palmer ◽  
Paula Ghaneh ◽  
Juan W. Valle ◽  
David Cunningham ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Adverse Events ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Combination Chemotherapy ◽  
Performance Status ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Rank Test ◽  
Full Analysis ◽  
Grade 3

LBA4006 Background: The ESPAC-3 trial compared adjuvant GEM with 5-fluorouracil/folinic acid for resected pancreatic cancer. GEM is the standard of care based on similar survival and less toxicity. ESPAC-4 aimed to determine whether combination chemotherapy with GEM/CAP improved survival compared to GEM monotherapy. Methods: Patients with pancreatic ductal adenocarcinoma were randomized within 12 weeks of surgery (stratified for R0/R1 resection margin status and country) to have either six 4 week cycles of IV GEM alone or GEM with oral CAP. The primary endpoint was overall survival; secondary endpoints were toxicity, relapse free survival, 2 and 5 year survival and quality of life. 722 patients (480 expected events), 361 in each arm, were needed to detect a 10% difference in 2 year survival rates with 90% power (log-rank test with 5% two-sided alpha). Results: Between Nov 10 2008 and Sep 11 2014, 732 patients were randomized with 730 included in the full analysis set (366 GEM, 364 GEM/CAP). Median age was 65 years, 57% were men. WHO performance status was 0, 1 or 2 in 42% 55% and 3% respectively. Postoperative median CA19-9 was 19 kU/L. Median maximum tumor size was 30 mm, 60% were R1 resections, 80% were node positive and 40% were poorly differentiated. On Dec 11 2015 the Independent Trial Steering Committee requested that the trial proceed to full analysis. The data freeze was on March 2 2016. Median survival (months) for patients treated with GEM/CAP was 28.0 (95% CI, 23.5 – 31.5) and 25.5 (22.7 – 27.9) for GEM. Stratified log-rank analysis revealed an HR=0.82 [95% CI, 0.68 – 0.98]; χ2 (1) = 4.61, P=0.032. 196 out of 366 GEM patients in the safety set reported 481 grade 3/4 adverse events, while 226 out of 359 GEM/CAP patients reported 608 grade 3/4 adverse events ( P=0.242). Conclusions: Adjuvant GEM/CAP for pancreatic cancer had a statistically significant improvement in survival compared to GEM monotherapy. Clinical trial information: ISRCTN96397434.

scholarly journals Local Ablative Strategies for Ductal Pancreatic Cancer (Radiofrequency Ablation, Irreversible Electroporation): A Review

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Salvatore Paiella ◽  
Roberto Salvia ◽  
Marco Ramera ◽  
Roberto Girelli ◽  
Isabella Frigerio ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Radiofrequency Ablation ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Locally Advanced ◽  
Irreversible Electroporation ◽  
Advanced Pancreatic Cancer ◽  
Ductal Adenocarcinoma ◽  
Dismal Prognosis ◽  
Ablative Techniques

Pancreatic ductal adenocarcinoma (PDAC) has still a dismal prognosis. Locally advanced pancreatic cancer (LAPC) accounts for the 40% of the new diagnoses. Current treatment options are based on chemo- and radiotherapy regimens. Local ablative techniques seem to be the future therapeutic option for stage-III patients with PDAC. Radiofrequency Ablation (RFA) and Irreversible Electroporation (IRE) are actually the most emerging local ablative techniques used on LAPC. Initial clinical studies on the use of these techniques have already demonstrated encouraging results in terms of safety and feasibility. Unfortunately, few studies on their efficacy are currently available. Even though some reports on the overall survival are encouraging, randomized studies are still required to corroborate these findings. This study provides an up-to-date overview and a thematic summary of the current available evidence on the application of RFA and IRE on PDAC, together with a comparison of the two procedures.

Radiotherapy in the treatment of benign meningioma of the skull base

1999 ◽  
Vol 90 (5) ◽  
pp. 823-827 ◽  
Author(s):  
Christopher Nutting ◽  
Michael Brada ◽  
Lucy Brazil ◽  
Ahmen Sibtain ◽  
Frank Saran ◽  
...  
Keyword(s):  
Skull Base ◽  
Performance Status ◽  
External Beam Radiation ◽  
Tumor Control ◽  
External Beam ◽  
Beam Radiation ◽  
Content Type ◽  
Skull Base Meningioma ◽  
Fine Print

Object. This study was undertaken to assess the long-term efficacy and toxicity of conventional fractionated external-beam radiation in the treatment of benign skull base meningioma.Methods. This is a retrospective study of 82 patients with histologically verified benign skull base meningioma treated by surgery followed by fractionated external-beam radiation at the Royal Marsden Hospital between 1962 and 1992. The 5- and 10-year progression-free survival (PFS) rates were 92% and 83%, respectively, with the site of disease being the only independent prognostic factor for tumor control according to multivariate analysis. The 10-year PFS rate for patients with sphenoid ridge meningiomas was 69% compared with 90% for those with tumors in the parasellar region. The overall 10-year survival rate was 71%, with performance status and patient age found to be significant independent prognostic factors. Six patients had worsening vision, which was due to cataract in five cases and retinopathy in one. There were no recorded cases of cranial nerve neuropathy.Conclusions. The excellent long-term tumor control and length of survival with minimal toxicity associated with conventional external-beam radiation should serve as a baseline for evaluation of new treatment strategies such as radiosurgery and skull base surgery.

scholarly journals Systemic therapy in metastatic pancreatic adenocarcinoma: current practice and perspectives

2021 ◽  
Vol 13 ◽  
pp. 175883592110185
Author(s):  
Lisa Lellouche ◽  
Lola-Jade Palmieri ◽  
Solène Dermine ◽  
Catherine Brezault ◽  
Stanislas Chaussade ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
Parp Inhibitor ◽  
Performance Status ◽  
Ductal Adenocarcinoma ◽  
Induction Treatment ◽  
Tumor Control ◽  
Small Subset ◽  
Second Line ◽  
Molecular Alterations ◽  
First Line Therapy

Major breakthroughs have been achieved in the management of metastatic pancreatic ductal adenocarcinoma (PDAC) with FOLFIRINOX (5-fluorouracil + irinotecan + oxaliplatin) and gemcitabine plus nab-paclitaxel approved as a first-line therapy, although the prognosis is still poor. At progression, patients who maintain a good performance status (PS) can benefit from second-line chemotherapy. To address the concern of achieving tumor control while maintaining a good quality of life, maintenance therapy is a concept that has now emerged. After a FOLFIRINOX induction treatment, maintenance with 5-fluorouracil (5-FU) seems to offer a promising approach. Although not confirmed in large, prospective trials, gemcitabine alone as a maintenance therapy following induction treatment with gemcitabine plus nab-paclitaxel could be an option, while a small subset of patients with a germline mutation of breast cancer gene ( BRCA) can benefit from the polyadenosine diphosphate-ribose polymerase (PARP) inhibitor olaparib. The rate of PDAC with molecular alterations that could lead to a specific therapy is up to 25%. The Food and Drug Administration (FDA) recently approved larotrectinib for patients with any tumors harboring a neurotrophic tyrosine receptor kinase ( NTRK) gene fusion, and pembrolizumab for patients with a mismatch repair deficiency in a second-line setting, including PDAC. Research focused on targeted therapy and immunotherapy is active and could improve patients’ outcomes in the near future.

scholarly journals Long-term yield of pancreatic cancer surveillance in high-risk individuals

Gut ◽  
2021 ◽  
pp. gutjnl-2020-323611
Author(s):  
Kasper A Overbeek ◽  
Iris J M Levink ◽  
Brechtje D M Koopmann ◽  
Femme Harinck ◽  
Ingrid C A W Konings ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
High Risk ◽  
Diagnostic Yield ◽  
Susceptibility Gene ◽  
Cancer Surveillance ◽  
Ductal Adenocarcinoma ◽  
Familial Pancreatic Cancer ◽  
Low Grade ◽  
Mutation Carriers

ObjectiveWe aimed to determine the long-term yield of pancreatic cancer surveillance in hereditary predisposed high-risk individuals.DesignFrom 2006 to 2019, we prospectively enrolled asymptomatic individuals with an estimated 10% or greater lifetime risk of pancreatic ductal adenocarcinoma (PDAC) after obligatory evaluation by a clinical geneticist and genetic testing, and subjected them to annual surveillance with both endoscopic ultrasonography (EUS) and MRI/cholangiopancreatography (MRI/MRCP) at each visit.Results366 individuals (201 mutation-negative familial pancreatic cancer (FPC) kindreds and 165 PDAC susceptibility gene mutation carriers; mean age 54 years, SD 9.9) were followed for 63 months on average (SD 43.2). Ten individuals developed PDAC, of which four presented with a symptomatic interval carcinoma and six underwent resection. The cumulative PDAC incidence was 9.3% in the mutation carriers and 0% in the FPC kindreds (p<0.001). Median PDAC survival was 18 months (range 1–32). Surgery was performed in 17 individuals (4.6%), whose pathology revealed 6 PDACs (3 T1N0M0), 7 low-grade precursor lesions, 2 neuroendocrine tumours <2 cm, 1 autoimmune pancreatitis and in 1 individual no abnormality. There was no surgery-related mortality. EUS detected more solid lesions than MRI/MRCP (100% vs 22%, p<0.001), but less cystic lesions (42% vs 83%, p<0.001).ConclusionThe diagnostic yield of PDAC was substantial in established high-risk mutation carriers, but non-existent in the mutation-negative proven FPC kindreds. Nevertheless, timely identification of resectable lesions proved challenging despite the concurrent use of two imaging modalities, with EUS outperforming MRI/MRCP. Overall, surveillance by imaging yields suboptimal results with a clear need for more sensitive diagnostic markers, including biomarkers.

scholarly journals Circulating Tumor DNA as a Sensitive Marker in Patients Undergoing Irreversible Electroporation for Pancreatic Cancer

2018 ◽  
Vol 47 (4) ◽  
pp. 1556-1564 ◽  
Author(s):  
Mao Lin ◽  
Mohammed Alnaggar ◽  
Shuzhen Liang ◽  
Jibing Chen ◽  
Kecheng Xu ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Overall Survival ◽  
Irreversible Electroporation ◽  
Circulating Tumor Dna ◽  
Carbohydrate Antigen ◽  
Ductal Adenocarcinoma ◽  
Diagnostic Tools ◽  
Tumor Biomarker ◽  
Monitoring Treatment ◽  
Tumor Dna

Background/Aims: Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed at an advanced stage, resulting in extremely poor 5-year survival. Late diagnosis of PDAC is mainly due to lack of a reliable method of early detection. Carbohydrate antigen (CA) 19-9 is often used as a tumor biomarker in PDAC; however, the test lacks sensitivity and specificity. Therefore, new sensitive and minimally invasive diagnostic tools are required to detect pancreatic cancer. Methods: Here, we investigated circulating tumor DNA (ctDNA) which contained KRAS-mutated as a potential diagnostic tool for PDAC patients who underwent irreversible electroporation (IRE). We used droplet digital polymerase chain reaction (ddPCR) to detect the expression of KRAS-mutated genes in plasma samples of 65 PDAC patients who underwent IRE. Results: In these 65 cases, ctDNA was detected in 20 (29.2%) samples. The median overall survival (OS) was 11.4 months with ctDNA+ patients and 14.3 months for ctDNA- patients. ctDNA+ patients had a obviously poorer prognosis associated to overall survival (P < 0.001). Conclusion: Our results suggested that the existence of ctDNA was a predictor of survival for PDAC patients. Therefore, ctDNA may be a new sensitive biomarker for monitoring treatment outcome in PDAC.

Potential role of chemoradiotherapy for metastatic pancreatic cancer.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 344-344
Author(s):  
D. Y. Lee ◽  
J. M. Robertson ◽  
J. Huang ◽  
J. H. Margolis ◽  
S. Balaraman ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cancer Patients ◽  
Performance Status ◽  
Metastatic Pancreatic Cancer ◽  
Categorical Variables ◽  
Ecog Performance Status ◽  
Term Survival ◽  
Kaplan Meier ◽  
Radiotherapy Dose

344 Background: Patients with metastatic pancreatic cancer have a poor outcome and the radiotherapy is typically only given to patients requiring palliation. We analyzed our institutional pancreas database to compare the outcome between chemotherapy alone vs. chemoradiotherapy. Methods: From January 2000 to December 2008, 199 metastatic pancreatic cancer patients were retrospectively analyzed. 13 (6.5%) patients received chemoradiotherapy and 186 (93.5%) patients received chemotherapy alone. Chemotherapy regimens consisted of 5-fluorouracil, gemcitabine, erlotinib, or cisplatin. The follow-up time was calculated from the time of diagnosis to the date of death or the last contact. Kaplan-Meier analysis was used to calculate the overall survival (OS). Results: Median OS was 5.3 months for all patients. Median OS was 4.9 months (0.4–27.0) for patients treated with chemotherapy alone and 7.8 months (0.6–44.1) for those treated with chemoradiotherapy (p = 0.013). Univariate survival analysis of categorical variables for patients treated with chemoradiotherapy revealed that age, race, gender, location of metastatic site, T stage (T3 v. T4) or nodal stage were not significant. However, ECOG performance status (1 v. 2/3) and the dose of radiation (<35 v. >35 Gy) received were associated with improved survival (p = 0.013, p=0.049). Median OS was 12.9 months for ECOG 1 vs. 5.6 months for ECOG 2/3. Median OS was 11.1 months for patients treated with radiotherapy dose > 35 Gy vs. 5.9 months for those who received less than 35 Gy. 3/13 (23%) patients who received chemoradiotherapy lived nearly two years or more. Conclusions: Metastatic pancreatic cancer patients with good performance score may benefit from chemoradiotherapy. Long-term survival was observed in this selected group. No significant financial relationships to disclose.

Symptom changes that predict disease control by systemic chemotherapy in patients with advanced pancreatic cancer.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 195-195
Author(s):  
Akiko Kuwahara ◽  
Shuichi Mitsunaga ◽  
Izumi Ohno ◽  
Satoshi Shimizu ◽  
Hideaki Takahashi ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Disease Control ◽  
Sleep Disturbance ◽  
Systemic Chemotherapy ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Symptom Changes

195 Background: Alleviation of symptoms is related to good tumor control in patients undergoing systemic chemotherapy for pancreatic cancer (PC). The predictive value of symptom change has not been fully understood. The aim of this study was to identify symptom changes that predicted disease control by systemic chemotherapy in PC patients. Methods: Patients with unresectable PC who had not received any anti-cancer therapy for PC were eligible for inclusion in this study. Patients with obvious infectious conditions were excluded. Symptoms were scored from 0 to 10 using the Japanese version of the MD Anderson Symptom Inventory before the start of chemotherapy and one month later. The response of the tumor was evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) vs. 1.0. Disease control was defined as CR, PR, or SD. An attempt was made to identify symptom changes that predicted disease control, and their impact on progression-free survival (PFS) was assessed. Results: The symptoms of 87 patients (male/female: 46/41, Karnofsky performance status (KPS): 100/90/80/70-50: 32/29/17/9, median age: 66 years) were prospectively assessed. Gemcitabine monotherapy (GEM), a GEM-based regimen, and S-1 monotherapy were performed in 42, 41, and 4 patients, respectively. Disease control was observed in 31 patients. The pain scores (P=0.047) and sleep disturbance scores (P=0.052) one month later were lower than before treatment in patients with disease control. Patients without deterioration of pain or sleep disturbance had a higher frequency of disease control (P=0.098 and P=0.004, respectively) and a longer PFS (P=0.021 and P<0.001, respectively) than patients whose pain or sleep disturbance became more severe. Conclusions: Improvements in pain and sleep disturbance scores at one month predict disease control by systemic chemotherapy in patients with advanced PC.

Characteristics of long-term survivors in a randomized phase III trial (NAPOLI-1) of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) treated with liposomal irinotecan (nal-IRI; MM-398) + 5-FU/LV.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 293-293
Author(s):  
Andrea Wang-Gillam ◽  
Chung-Pin Li ◽  
Gyorgy Bodoky ◽  
Andrew Dean ◽  
Kyung-Hun Lee ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Performance Status ◽  
The United States ◽  
Small Sample ◽  
Phase Iii ◽  
Ductal Adenocarcinoma ◽  
Primary Analysis ◽  
Liposomal Irinotecan ◽  
Long Term Survivors

293 Background: nal-IRI, a liposomal formulation of irinotecan, plus 5-FU/LV is approved in the United States and Taiwan for patients (pts) with mPDAC previously treated with gemcitabine-based therapy. Primary analysis of the NAPOLI-1 trial (NCT01494506) showed that nal-IRI+5-FU/LV significantly improved median overall survival vs 5-FU/LV (6.1 vs 4.2 months; HR, 0.67; 95% CI, 0.49-0.92; P = 0.012; Wang-Gillam et al, Lancet. 2016). Herein we report baseline characteristics of pts surviving ≥1 year (data cutoff, Nov 2015). Methods: This analysis includes 117 pts assigned to treatment with nal-IRI 70 mg/m2 (free base) + 5-FU/LV 2400/400 mg/m2 q2w, and 119 pts assigned to treatment with 5-FU/LV 2000/200 mg/m2weekly for weeks 1-4 q6w. Results: A total of 29 (25%) pts in the nal-IRI+5-FU/LV arm and 17 (14%) in the 5-FU/LV arm survived ≥1 year. These pts typically had better performance status, lower CA19-9 (U/mL) levels, and were less likely to have liver metastases at baseline, compared with the overall population (Table). For long-term survivors in the nal-IRI+5-FU/LV arm, a higher proportion of pts had neutrophil-to-lymphocyte ratio (NLR) >5, a marker of poor prognosis, suggesting that higher NLR may potentially be predictive of survival outcome with nal-IRI+5-FU/LV. Conclusions: More pts receiving nal-IRI+5-FU/LV versus 5-FU/LV were alive beyond 1 year. The most prominent prognostic markers of survival ≥1 year included lower CA19-9, KPS ≥90 and absence of liver metastases. These analyses may be limited by small sample sizes. Clinical trial information: NCT01494506. [Table: see text]

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