Locally Advanced Pancreatic Carcinoma Patients Research Articles

Hypofractionated intensity-modulated radiotherapy with concurrent chemotherapy for elderly patients with locally advanced pancreatic carcinoma

BackgroundIt is important to understand how elderly patients with locally advanced pancreatic carcinoma (LAPC) should be treated, since the number of elderly cancer patients will increase. However, the optimal treatment for elderly patients with LAPC remains unclear. The purpose of this study was to evaluate the efficacy and safety of hypofractionated intensity-modulated radiotherapy (IMRT) with concurrent gemcitabine for elderly patients with LAPC.MethodsWe retrospectively analysed the data from LAPC patients aged ≥ 75 years treated with hypofractionated IMRT (48 Gy in 15 fractions) with concurrent weekly gemcitabine at our institution from February 2013 to December 2018. Overall survival (OS), progression-free survival (PFS), locoregional progression-free survival (LRPFS), distant metastasis-free survival (DMFS), and the pattern of recurrence and toxicity were analysed.ResultsFifteen patients received treatment during the study period. The median age was 78 years (range 75–86 years), and the Eastern Cooperative Oncology Group (ECOG) performance status (PS) of all patients was 0–1. The median survival time (MST) and median PFS were 20.4 [95% confidence interval (CI) 10.3–36.8] and 13.5 (95% CI 6.4–20.3) months, respectively, and the 1-year OS and PFS rates were 80.0% (95% CI 50–93.1%) and 66.7% (95% CI 37.5–84.6%), respectively. The median LRPFS and median DMFS were 15.6 (95% CI 6.4–36.8) and 14.9 (95% CI 7.0–20.5) months, respectively, and the 1-year LRPFS and DMFS rates were 73.3% (95% CI 43.6–89.1%) and 66.7% (95% CI 37.5–84.6%), respectively. Non-haematologic grade 3 toxicity was observed in three cases, of which only one was induced by radiotherapy, whereas grade 4–5 non-haematologic acute or late toxicities were not observed.ConclusionsThe OS and PFS of elderly patients with LAPC treated using hypofractionated IMRT with concurrent gemcitabine were favourable and without the occurrence of severe toxicity. This treatment strategy is feasible and promising for elderly LAPC patients with good PS.

Low Systemic Inflammation Response Index Predicts Good Prognosis in Locally Advanced Pancreatic Carcinoma Patients Treated with Concurrent Chemoradiotherapy.

Background We investigated the prognostic significance of pretreatment systemic inflammation response index (SIRI) in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (CRT). Methods Present retrospective cohort analysis investigated consecutive 154 LAPC patients who received radical CRT. The SIRI was defined as: SIRI = neutrophil × monocyte/lymphocyte counts. Ideal SIRI cutoff(s) influencing overall survival (OS) and progression-free survival (PFS) results were sought by using receiver operating characteristic (ROC) curve analysis. The primary endpoint was the interaction between the SIRI and OS results. Results The median follow-up, PFS, and OS durations were 14.3 (range: 2.9-74.6), 7.9 [%95 confidence interval (CI): 5.7-10.1), and 14.7 months (%95 CI: 11.4-18.0) for the entire cohort, respectively. ROC curve analyses determined the ideal SIRI cutoff that exhibiting a significant link with OS and PFS outcomes at the rounded 1.6 point (AUC: 74.3%; sensitivity: 73.8%; specificity: 70.1%).The SIRI <1.6 patients (N = 58) had significantly superior median PFS (13.8 versus 6.7 months; P < 0.001) and OS (28.6 versus 12.6 months; P < 0.001) lengths than SIRI ≥1.6 patients (N = 96), respectively. Although the N0 (versus N1; P < 0.05) and CA 19-9 ≤90 U/mL (versus >90 U/mL) appeared as the other significant associates of better OS and PFS in univariate analyses, yet the results of multivariate analyses confirmed the SIRI <1.6 as the independent indicator of superior OS and PFS (P < 0.001 for each). Conclusion Pretreatment SIRI is a novel independent prognosticator that may further enhance the conventional tumor-node-metastases staging system in a more precise prediction of the OS and PFS outcomes of LAPC patients after radical CRT.

139P - Prognostic usefulness of advanced lung cancer inflammation index in locally-advanced pancreatic carcinoma patients treated with radical chemoradiotherapy

BackgroundWe retrospectively investigated the prognostic value of pre-treatment advanced lung cancer inflammation index (ALI) in locally advanced pancreatic carcinoma (LAPC) patients who underwent concurrent chemoradiotherapy (CCRT). MethodsPresent retrospective cohort analysis incorporated consecutive 141 LAPC patients who received radical CCRT. Accessibility of baseline ALI cutoff(s) impacting survival outcomes was sought by receiver operating characteristic (ROC) curve analysis. Interaction between the ALI and overall- (OS) and while progression-free survival (PFS) constituted our primary and secondary end points, respectively. ResultsAt a median follow-up of 14.4 months (range: 3.2-74.2), the median PFS and OS were 7.5 (%95 CI: 5.9-9.1) and 14.6 months (%95 CI: 11.6-17.6), respectively. ROC curve analyses set the ideal ALI cutoff value at 25.3 (AUC: 75.6; sensitivity: 72.7%; specificity: 70.3%) that exhibited a significant association with both the OS and PFS results. Patient stratification into two groups per ALI [≤25.3 (N = 75) versus >25.3 (N = 66)] showed that the ALI>25.3 group had a significantly superior median OS (25.8 versus 11.4 months; P < 0.001) and PFS (15.9 versus 6.0 months; P < 0.001) than its ALI≤25.3 counterpart. Other factors exhibiting significantly better OS and PFS rates were N0(versus N1) stage (P < 0.05 for each endpoint) and CA 19-9 ≤90 U/mL (versus >90 U/mL), respectively (P < 0.05 for each end point). These three factors were also affirmed to be independent indicators of longer OS and PFS (P < 0.05 for each) in multivariate analyses. ConclusionsResults of this hypothesis-generating research proposed the pre-CCRT ALI as a novel robust associate of OS and PFS outcomes for LAPC patients undergoing CCRT. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Stereotactic radiotherapy of pancreatic cancer: a systematic review on pain relief.

Locally advanced pancreatic carcinoma (LAPC) has a poor prognosis and the purpose of treatment is survival prolongation and symptom palliation. Radiotherapy has been reported to reduce pain in LAPC. Stereotactic RT (SBRT) is considered as an emerging radiotherapy technique able to achieve high local control rates with acceptable toxicity. However, its role in pain palliation is not clear. To review the impact on pain relief with SBRT in LAPC patients, a literature search was performed on PubMed, Scopus, and Embase (January 2000–December 2017) for prospective and retrospective articles published in English. Fourteen studies (479 patients) reporting the effect of SBRT on pain relief were finally included in this analysis. SBRT was delivered with both standard and/or robotic linear accelerators. The median prescribed SBRT doses ranged from 16.5 to 45 Gy (median: 27.8 Gy), and the number of fractions ranged from 1 to 6 (median: 3.5). Twelve of the 14 studies reported the percentage of pain relief (in patients with pain at presentation) with a global overall response rate (complete and partial response) of 84.9% (95% CI, 75.8%–91.5%), with high heterogeneity (Q2 test: P<0.001; I2=83.63%). All studies reported toxicity data. Acute and late toxicity (grade ≥3) rates were 3.3%–18.0% and 6.0%–8.2%, respectively. Reported gastrointestinal side effects were duodenal obstruction/ulcer, small bowel obstruction, duodenal bleeding, hemorrhage, and gastric perforation. SBRT achieves pain relief in most patients with pancreatic cancer with an acceptable gastrointestinal toxicity rate. Further prospective studies are needed to define optimal dose/fractionation and the best systemic therapies modality integration to reduce toxicity and improve the palliative outcome. Finally, the quality of life and, particularly, pain control should be considered as an endpoint in all future trials on this emerging treatment technique.

Circulating tumor cells in locally advanced pancreatic adenocarcinoma: the ancillary CirCe 07 study to the LAP 07 trial

BackgroundPancreatic carcinoma is one of the leading causes of cancer-related mortality. At the time of diagnosis, 30% of patients present with a locally advanced pancreatic carcinoma (LAPC). As circulating tumor cells (CTCs) count may be a surrogate of the cancer metastatic abilities, CTC detection rates and prognostic value were studied in a prospective cohort of LAPC patients. Patients and methodsAn LAP07 international multicenter randomized study assesses in patients whose LAPC is controlled after 4 months of chemotherapy whether chemoradiotherapy could increase survival versus continuation of chemotherapy. A subgroup of patients included in the LAP07 trial was screened for CTCs (CellSearch®) before the start of the chemotherapy and after 2 months of treatment. Patient characteristics and survival were obtained prospectively and were correlated with CTC detection. ResultsSeventy-nine patients were included. One or more CTCs/7.5 ml were detected in 5% of patients before treatment and in 9% of patients after 2 months of treatment (overall detection rate: 11% of patients). CTC positivity was associated with poor tumor differentiation (P = 0.04), and with shorter overall survival (OS) in multivariable analysis (RR = 2.5, P = 0.01), together with anemia. ConclusionsThe evaluation of micrometastatic disease using CTC detection appears as a promising prognostic tool in LAPC patients.

Combined radiochemotherapy in patients with locally advanced pancreatic cancer: A meta-analysis

To compare the long-term clinical efficacy of chemotherapy plus radiotherapy (CRT) with that of radiotherapy alone (RT) or chemotherapy alone (CT) for locally advanced pancreatic carcinoma (LAPC). Using manual and computer-aided methods, we searched the data through the databases, including PubMed/EmBase/CNKI/CQVIP/China Journals Full Text Database and websites and proceedings of major annual meetings such as ASCO and CSCO. The methodological quality of the included studies was assessed using the Jadad scoring system. Both English and Chinese publications were searched. We collected data from controlled clinical trials on CRT vs RT or CT for LAPC, and conducted a meta-analysis of 15 included studies. Meta-analysis was performed using RevMan4.2 Software according to the method recommended by Cochrane Collaboration. Fifteen eligible randomized controlled trials including a total of 1128 patients were screened. Jadad score was 2 in only one article, and 3-4 in the remaining 14 studies. The meta-analysis showed that CRT was superior in the 6- and 12-mo survivals to the RT alone group or CT alone group (P = 0.0001 and P = 0.02, respectively), whereas the 18-mo survival showed no significant difference (P = 0.23). Subgroup analysis showed that the 6-, 12-, and 18-mo survivals were not significantly different between the CRT group and CT group (P = 0.07, P = 0.23, and P = 0.91, respectively). Notably, the CRT group had significantly better 6-, 12-, and 18-mo survivals than the RT group (all P < 0.01). CRT group had significantly more grade 3-4 treatment-related hematologic and non-hematologic toxicities than the CT group or RT group (all P < 0.01). Compared with CT or RT, CRT can benefit the long-term survival of LAPC patients, although it may also increase treatment-related toxicities.

711P - Does FDG-PET-CT based Re-Staging Influences Initial Management Decision and Clinical Outcome in Patients with locally advanced Pancreatic Carcinoma Planned to Undergo Chemoradiotherapy?

ABSTRACT Background Impact of re-staging with 18F-fluoro-deoxy-glucose positron emission tomography (PET-CT) on management decision and clinical outcomes in patients with locally-advanced pancreatic carcinoma (LAPC) initially planned to undergo concurrent chemoradiotherapy (CRT) was investigated. Materials and methods Seventy-one consecutive patients with conventionally staged LAPC were re-staged with PET-CT before CRT. Patients were categorized into non-metastatic (M0) and metastatic (M1) groups according to PET-CT findings. M0patients underwent 50.4 Gy (1.8 Gy/fr) of radiotherapy and concurrent 5-FU followed by maintenance gemcitabine. Results Re-staging PET-CT revealed conventional imaging occult distant metastases in 19 cases (26.8%). Of 52 patients with LAPC confirmed by PET-CT, additional regional lymph nodes were identified to be involved in 7 (13.4%), mandating enlargement of radiation field. Taken together, PET-CT results changed or revised initial management decision in 37.2% patients. Median follow-up times for the whole, M0 and M1 cohorts were 11.3, 14.5, and 6.2 months, respectively. Median overall, locoregional progression-free, and progression-free survivals for the same cohorts were 11.4, 7.8, and 5.1 months,16.1, 9.9, and 7.4 months, and 6.2, 3.4, and 2.5 months, respectively. Survival differences between M0 and M1 cohorts were statistically significant (p Conclusions Current results demonstrated the importance of PET-CT based re-staging of LAPC in selection of suitable patients for CRT, prevention of useless aggressive treatment in metastatic cases, and precise estimation of survival outcomes of LAPC patients following radical CRT. Disclosure All authors have declared no conflicts of interest.

Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy.

BackgroundWe aimed to study the predictive value of combined 18F-fluoro-deoxy-D-glucose positron emission tomography and computerized tomography (FDG-PET-CT), on outcomes in locally advanced pancreatic carcinoma (LAPC) patients treated with concurrent chemoradiotherapy (C-CRT).MethodsThirty-two unresectable LAPC patients received 50.4 Gy (1.8 Gy/fr) of RT and concurrent 5-FU followed by 4 to 6 cycles of gemcitabine consolidation. Response was evaluated by FDG-PET-CT at post-C-CRT 12-week. Patients were stratified into two groups according to the median difference between pre- and post-treatment maximum standard uptake values (SUVmax) as an indicator of response for comparative analysis.ResultsAt a median follow-up of 16.1 months, 16 (50.0%) patients experienced local/regional failures, 6 of which were detected on the first follow-up FDG-PET-CT. There were no marginal or isolated regional failures. Median pre- and post-treatment SUVmax and median difference were 14.5, 3.9, and -63.7%, respectively. Median overall survival (OS), progression-free survival (PFS), and local-regional progression-free survival (LRPFS) were 14.5, 7.3, and 10.3 months, respectively. Median OS, PFS, and LRPFS for those with greater (N = 16) versus lesser (N = 16) SUVmax change were 17.0 versus 9.8 (p = 0.001), 8.4 versus 3.8 (p = 0.005), and 12.3 versus 6.9 months (p = 0.02), respectively. On multivariate analysis, SUVmax difference was predictive of OS, PFS, and LRPFS, independent of existing covariates.ConclusionsSignificantly higher OS, PFS, and LRPFS in patients with greater SUVmax difference suggest that FDG-PET-CT-based metabolic response assessment is an independent predictor of clinical outcomes in LAPC patients treated with definitive C-CRT.