Loss of Stat3 Tyrosine Phosphorylation in Tumor Relates Poor Prognosis in Patients with Advanced Pancreatic Cancer

248 Background: The prognosis of patients with advanced pancreatic cancer (APC) is extremely poor. Several clinical and laboratory factors have been known to be associated with prognosis of APC patients. However, there are few clinically available prognostic models predicting survival in APC patients receiving palliative chemotherapy. Methods: To construct a prognostic model to predict survival in APC patients receiving palliative chemotherapy, we analyzed the clinical data from 306 consecutive patients with pathologically confirmed APC who received palliative chemotherapy. We selected six independent prognostic factors which remained independent prognostic factors after multivariate analysis. Thereafter, we rounded the regression coefficient (β) for each independent prognostic factor derived from the Cox regression equation (HR = eβ) and developed a prognostic index (PI). Results: Developed prognostic index (PI) was as follows: PI = 2 (if performance status score 2–3) + 1 (if metastatic disease) + 1 (if initially unresectable disease) + 1 (if carcinoembryonic antigen level ≥5.0 ng/ml) + 1 (if carbohydrate antigen 19-9 level ≥1000 U/ml) + 2 (if neutrophil–lymphocyte ratio ≥5). The patients were classified into three prognostic groups: favorable (PI 0–1, n = 73), intermediate (PI 2–3, n = 145), and poor prognosis (PI 4–8, n = 88). The median overall survival for each prognostic group was 16.5, 12.3 and 6.2 months, respectively, and the 1-year survival rates were 67.3%, 51.3%, and 19.1%, respectively (P < 0.01). The c index of the model was 0.658. This model was well calibrated to predict 1-year survival, in which overestimation (2.4% and 0.2% in the favorable and poor prognosis groups, respectively) and underestimation (3.6% in the intermediate prognosis group) were observed. Conclusions: This prognostic model based on readily available clinical factors would help clinicians in estimating the overall survival in APC patients receiving palliative chemotherapy.

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Points to keep in mind when carrying out clinical trials in Japan on advanced pancreatic cancer cases without alternative treatments: Analysis of 367 cases.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.243 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 243-243

Author(s):

Giichiro Tsurita ◽

Hiroshi Yasui ◽

Tomohiro Kurokawa ◽

Yuichiro Yoshioka ◽

Kentaro Yazawa

Keyword(s):

Pancreatic Cancer ◽

Clinical Trial ◽

Clinical Trials ◽

General Condition ◽

Outpatient Clinic ◽

Poor Prognosis ◽

Medical Condition ◽

Advanced Pancreatic Cancer ◽

Screening Tests ◽

Trial Participation

243 Background: We commenced a physician-led clinical trial to examine the efficacy of a combined treatment of peptide vaccine therapy for advanced pancreatic cancer that has no effective treatment. During this trial, there were inquiries from 367 cases, of which 145 cases (40%) were examined at our outpatient clinic. The purpose of this study was to examine these cases in detail and to consider the points to be noted in executing clinical trials for poor prognosis cases. Methods: We examined the timing of inquiry, medical condition, the person(s) they inquired, and other relevant information regarding the 367 subjects who made inquiries. For the 145 cases visited the outpatient clinic of our hospital, we examined their medical condition, treatment and whether or not they have participated in a clinical trial. Results: 140 of the 367 cases (38%) of inquiry were concentrated within the first two months after the start. During these two months, there was a concentration of patients who had completed standard treatments and were a few months into BSC, but were unable to participate in the clinical trial due to deterioration of their general condition. Many of the inquiries were made by family members (spouse or child) of the patients, around twice the number of inquiries made by patients themselves. Even among the 145 subjects that were examined in the outpatient clinic of our hospital, severe cases, in particular, were seen several months after the start of the study. There were many cases that required urgent hospitalization during outpatient visits or patients whose general condition rapidly deteriorated during the screening tests. 23 cases (16%) underwent the clinical trial. Conclusions: In clinical trials such as this one, which handles cases with poor prognosis, many of the subjects are in poor general condition at the inquiry stage, and most of these inquiries are concentrated immediately after the start of the study. Therefore, it is very important to deal with inquiries and make judgments during the outpatient examination on whether or not clinical trial participation is possible.

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Clinico-pathological analyses of the relationship between SMAD4, TP53, CDKN2A mutations and recurrence and prognosis in patients with pancreatic cancer: A single institutional study.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.4_suppl.319 ◽

2018 ◽

Vol 36 (4_suppl) ◽

pp. 319-319

Author(s):

Masaru Fukahori ◽

Yoshiki Naito ◽

Hiroto Ishikawa ◽

Tomoyuki Ushijima ◽

Sachiko Nagasu ◽

...

Keyword(s):

Pancreatic Cancer ◽

Poor Prognosis ◽

Advanced Pancreatic Cancer ◽

Gene Mutations ◽

Significant Prognostic Factor ◽

Mutation Status ◽

Formalin Fixed Paraffin ◽

Formalin Fixed Paraffin Embedded ◽

The Relationship ◽

Smad4 Mutation

319 Background: Gene mutations of SMAD4, TP53 and CDKN2A( p16) have been reported to be associated with poor prognosis and metastatic burden in advanced pancreatic cancer (PC). On the other hand, the association between these gene mutations and recurrence in PC is still unclear. The present study aimed to whether the 3 gene mutations were related to the recurrence and the prognosis in PC patients. Methods: Formalin-fixed paraffin-embedded tumor samples were gathered from patients with PC who underwent curative resection between January 2014 and December 2015. We retrospectively evaluated a relationship between the mutation status of SMAD4, TP53 and p16 and the recurrence and prognosis in patients with PC. Results: Totally, fifty-six samples of patients with PC (Stage I/ II/ III: 5/6/45 (UICC 7th)) were included in this analysis. Recurrence was seen in 32 patients (57.1%). Patients with PC both recurrence and advanced pathological stage showed poor prognosis. Each 3 gene mutation did not show a significant association with recurrence. TP53 and p16 single mutations did not show significant association with prognosis. However, the patients with PC who have SMAD4 mutation showed a significant poor prognosis (Overall survival: 18.6 vs. 34.5 months, p = 0.03). Multivariate analysis showed only recurrence was a significant prognostic factor (p = 0.01) Conclusions: The present study suggested that there was no association between SMAD4 and recurrence, whereas in case of recurrence, SMAD4 mutation may be associated with prognosis in PC patients.

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Modulated Electro-Hyperthermia as Palliative Treatment for Pancreatic Cancer: A Retrospective Observational Study on 106 Patients

Integrative Cancer Therapies ◽

10.1177/1534735419878505 ◽

2019 ◽

Vol 18 ◽

pp. 153473541987850 ◽

Cited By ~ 5

Author(s):

Giammaria Fiorentini ◽

Donatella Sarti ◽

Virginia Casadei ◽

Carlo Milandri ◽

Patrizia Dentico ◽

...

Keyword(s):

Pancreatic Cancer ◽

Partial Response ◽

Pancreatic Adenocarcinoma ◽

Stable Disease ◽

Poor Prognosis ◽

Median Overall Survival ◽

Progressive Disease ◽

Tumor Response ◽

Advanced Pancreatic Cancer ◽

Efficacy And Safety

Background: Pancreatic adenocarcinoma has a poor prognosis, resulting in a <10% survival rate at 5 years. Modulated electro-hyperthermia (mEHT) has been increasingly used for pancreatic cancer palliative care and therapy. Objective: To monitor the efficacy and safety of mEHT for the treatment of advanced pancreatic cancer. Methods: We collected data retrospectively on 106 patients affected by stage III-IV pancreatic adenocarcinoma. They were divided into 2 groups: patients who did not receive mEHT (no-mEHT) and patients who were treated with mEHT. We performed mEHT applying a power of 60 to 150 W for 40 to 90 minutes. The mEHT treatment was associated with chemotherapy and/or radiotherapy for 33 (84.6%) patients, whereas 6 (15.4%) patients received mEHT alone. The patients of the no-mEHT group received chemotherapy and/or radiotherapy in 55.2% of cases. Results: Median age of the sample was 65.3 years (range = 31-80 years). After 3 months of therapy, the mEHT group had partial response in 22/34 patients (64.7%), stable disease in 10/34 patients (29.4%), and progressive disease in 2/34 patients (8.3%). The no-mEHT group had partial response in 3/36 patients (8.3%), stable disease in 10/36 patients (27.8%), and progressive disease in 23/36 patients (34.3%). The median overall survival of the mEHT group was 18.0 months (range = 1.5-68.0 months) and 10.9 months (range = 0.4-55.4 months) for the non-mEHT group. Conclusions: mEHT may improve tumor response and survival of pancreatic cancer patients.

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Immunotherapy in pancreatic cancer and the importance of tumour testing

BMJ Case Reports ◽

10.1136/bcr-2020-235774 ◽

2020 ◽

Vol 13 (7) ◽

pp. e235774

Author(s):

Phuong Ngo ◽

Mohamed Shanshal ◽

Adam Rojan

Keyword(s):

Pancreatic Cancer ◽

Genetic Testing ◽

Adjuvant Chemotherapy ◽

Mismatch Repair ◽

Poor Prognosis ◽

Treatment Options ◽

Locally Advanced ◽

Advanced Pancreatic Cancer ◽

Additional Treatment ◽

Clinical Suspicion

Advanced pancreatic cancer carries a poor prognosis and has traditionally been treated with chemotherapy. However, immunotherapy has made great strides in a subset of patients depending on mismatch repair/microsatellite status. We present a patient with locally advanced pancreatic cancer treated with neoadjuvant chemotherapy followed by surgery and additional adjuvant chemotherapy whose disease progressed while on adjuvant chemotherapy. Tumour testing showed a mismatch repair mutation and high microsatellite instability, making her eligible for treatment with immunotherapy. Germline genetic testing confirmed the clinical suspicion of Lynch syndrome. She has had isolated sites of progression treated with radiation but overall has been receiving immunotherapy for more than 3 years, highlighting the importance of tumour testing as it may allow for additional treatment options and improved survival.

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Cortical blindness due to cerebral infarct in advanced pancreatic cancer

BMJ Case Reports ◽

10.1136/bcr-2017-223843 ◽

2019 ◽

Vol 12 (7) ◽

pp. e223843 ◽

Cited By ~ 1

Author(s):

Nivedita Nimesh ◽

Sanjeev Kumar Verma ◽

Sanjiv Kumar Gupta

Keyword(s):

Pancreatic Cancer ◽

Poor Prognosis ◽

Anticoagulation Therapy ◽

Anterior Segment ◽

Advanced Pancreatic Cancer ◽

Cortical Blindness ◽

Low Molecular Weight ◽

Light Reaction ◽

Mri Brain ◽

Pupillary Light

A 65-year-old man, a known case of advanced pancreatic cancer on cisplatin and gemcitabine-based chemotherapy, presented with sudden bilateral painless loss of vision with altered sensorium. Clinical examination showed a normal pupillary light reaction, normal anterior segment and normal fundus. MRI brain showed bilateral parieto-occipital infarct. This report highlights the incidence of cortical blindness due to thromboembolism at the cerebral level in pancreatic cancer. Cerebral ischaemic events occur at an advanced stage of pancreatic cancer already diagnosed at stroke onset and portend a poor prognosis. Anticoagulation therapy, especially low molecular weight heparin, remains the best strategy to prevent recurrences.

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