Prognostic Utility of Prechemoradiotherapy Albumin-to-Alkaline Phosphatase Ratio in Unresectable Locally Advanced Pancreatic Carcinoma Patients

Background. We investigated the prognostic usefulness of prechemoradiotherapy (CRT) albumin-to-alkaline phosphatase ratio (AAPR) in unresectable locally advanced pancreatic adenocarcinoma (LAPAC) patients managed with definitive concurrent CRT (CCRT). Methods. A sum of 136 LAPAC patients who consecutively underwent definitive CCRT was retrospectively analyzed. The AAPR (serum albumin (g/dL)/serum alkaline phosphatase (IU/L)) was calculated by using the parameters obtained from the routine biochemistry tests on the first day of the CCRT. Ideal AAPR cutoff was sought by utilizing receiver operating characteristic (ROC) curve analysis. The primary and secondary endpoints were the impact of the AAPR on the overall survival (OS) and progression-free survival (PFS) results, respectively. Results. At a median follow-up of 14.8 months (range: 3.2-85.7), the median PFS and OS times were 7.5 (95% confidence interval (CI): 6.0-9.0) and 14.9 months (95% CI: 11.9-17.9), respectively. The ideal common AAPR cutoff was identified at the rounded 0.46 (area under the curve: 72.3%; sensitivity: 71.2%; specificity: 70.3%) point that dichotomized the patients into two groups: low AAPR (L-AAPR; N = 71 ) and high AAPR (H-AAPR; N = 65 ) groups, respectively. Comparative survival analyses showed that the L-AAPR cohort had significantly shorter median PFS (6.8 (95% CI: 5.7-7.9) versus 11.3 (95% CI: 9.9-12.7) months; P = 0.005 ) and OS (12.8 (95% CI: 10.6-15.0) versus 19.2 (95% CI: 16.9-21.5) months; P = 0.001 ) durations than their H-AAPR counterparts, separately. Albeit the N1-2 ( P = 0.004 ) and CA 19 ‐ 9 > 90 U / mL ( P = 0.008 ) were also found to be associated with inferior outcomes, yet the results of the multivariate analyses ascertained the L-AAPR as an independent indicator of diminished PFS ( P = 0.003 ) and OS ( P = 0.002 ) results. Conclusion. The present results proposed that the pretreatment AAPR < 0.46 was a novel independent indicator of adverse PFS and OS in unresectable LAPAC patients undergoing definitive CCRT.

Locally advanced pancreatic carcinoma with jaundice: the benefit of a sequential treatment with stenting followed by CT-guided 125I seeds implantation

Objectives To evaluate the role of sequential therapy with percutaneous biliary stenting and CT-guided iodine-125 seed implantation for locally advanced pancreatic carcinoma with concomitant obstructive jaundice. Methods Between January 2016 and December 2018, 42 patients diagnosed with locally advanced pancreatic carcinoma with concomitant obstructive jaundice were enrolled retrospectively. All patients received biliary stenting via percutaneous transhepatic biliary drainage (PTBD) to alleviate obstructive jaundice. Thereafter, twenty-two patients underwent CT-guided iodine-125 seed implantation (treatment group), and 20 did not (control group). The prescribed dose in the treatment group was 110–130 Gy. The clinical data, duration of biliary stent patency, and overall survival (OS) were evaluated. Results Overall, the total bilirubin level decreased from 275.89 ± 115.44 to 43.08 ± 43.35 μmol/L (p < 0.001) 1 month after percutaneous biliary stenting. In the treatment group, the postoperative median dose covering 90% of the target volume was 129.71 Gy. Compared with the control group, the treatment group had a long mean duration of biliary stent patency and median OS (11.42 vs. 8.57 months, p < 0.01; 11.67 vs. 9.40 months, p < 0.01, respectively). The overall positive response rates 6 months post-treatment in the treatment and control groups were 72.7% (16/22) and 30% (6/20), respectively. Adverse events of more than grade 3 were not observed during the follow-up. Conclusion Sequential therapy with percutaneous biliary stenting and CT-guided iodine-125 seed implantation is an effective and safe treatment alternative for locally advanced pancreatic carcinoma with concomitant obstructive jaundice, which is worthy of clinical application. Key Points • Obstructive jaundice was alleviated after biliary stent placement in all patients, and the total bilirubin level decreased. • The overall positive response rates at 6 months post-treatment were higher in the treatment group than in the control group, and adverse events of more than grade 3 were not observed during the follow-up period. • Sequential therapy with percutaneous biliary stenting and CT-guided iodine-125 seed implantation can prolong biliary stent patency and improve survival.

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

Background It 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. Methods We 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. Results Fifteen 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. Conclusions The 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.

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

Background: It 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. Methods: We 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.Results: Fifteen 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 one-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 one-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.Conclusions: The 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.