Intensity-Modulated and Image-Guided Radiotherapy in Patients with Locally Advanced Inoperable Pancreatic Cancer after Preradiation Chemotherapy

Background. Radiotherapy (RT) in patients with pancreatic cancer is still a controversial subject and its benefit in inoperable stages of locally advanced pancreatic cancer (LAPC), even after induction chemotherapy, remains unclear. Modern radiation techniques such as image-guided radiotherapy (IGRT) and intensity-modulated radiotherapy (IMRT) may improve effectiveness and reduce radiotherapy-related toxicities. Methods. Patients with LAPC who underwent radiotherapy after chemotherapy between 09/2004 and 05/2013 were retrospectively analyzed with regard to preradiation chemotherapy (PRCT), modalities of radiotherapy, and toxicities. Progression-free (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. Results. 15 (68%) women and 7 men (median age 64 years; range 40–77) were identified. Median duration of PRCT was 11.1 months (range 4.3–33.0). Six patients (27%) underwent conventional RT and 16 patients (73%) advanced IMRT and IGRT; median dosage was 50.4 (range 9–54) Gray. No grade III or IV toxicities occurred. Median PFS (estimated from the beginning of RT) was 5.8 months, 2.6 months in the conventional RT group (conv-RT), and 7.1 months in the IMRT/IGRT group (P=0.029); median OS was 11.0 months, 4.2 months (conv-RT), and 14.0 months (IMRT/IGRT); P=0.141. Median RT-specific PFS for patients with prolonged PRCT > 9 months was 8.5 months compared to 5.6 months for PRCT < 9 months (P=0.293). This effect was translated into a significantly better median RT-specific overall survival of patients in the PRCT > 9 months group, with 19.0 months compared to 8.5 months in the PRCT  <  9 months group (P=0.049). Conclusions. IGRT and IMRT after PRCT are feasible and effective options for patients with LAPC after prolonged preradiation chemotherapy

Second-line treatment in pancreatic cancer patients: Who profits? Results from the CONKO study group

OBJECTIVES: With increasing numbers of therapeutic options in inoperable pancreatic cancer (PAC), patients tend to receive more than just a first line (FL) therapy. METHODS: All patients who started FL for PAC at our institution (1997-2012) were retrospectively studied to identify patient's and treatment characteristics. Significant parameters in regard to second-line (SL) related survival were looked for as the basis for a prognostic model. This score was validated in a patient cohort from the CONKO-003 study. RESULTS: Two hundred eighty of 521 (53.7%) patients received SL therapy, median overall survival (OS) from the beginning of SL (OS2) was 5.1 months. Significant more SL patients had undergone surgery, a higher Karnofsky performance state (KPS) and a duration of FL longer than 4 months.Prognostic factors impacting OS2 were KPS, carbohydrate antigen 19-9 levels at start of SL and the duration of FL. These 3 factors establish a prognostic score-validated in CONKO-003-for SL patients with 3 subgroups: "good" (median OS2, 9.3 months), "intermediate" (median OS2, 7.1 months), "poor" prognosis (median OS2, 3.8 months; P < 0.001). CONCLUSIONS: Among patients with PAC, more than 50% receive SL therapy. Our prognostic model identifies 3 subgroups and can identify patients with a maximum benefit of SL therapy

Weiterentwicklung und Erprobung von Immissionsmessverfahren fuer gesundheitsgefaehrdende organische Stoffe

Available from TIB Hannover: RN 6729(94) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman

α-smooth muscle actin expression and desmoplastic stromal reaction in pancreatic cancer: results from the CONKO-001 study

Background: Previous investigations in pancreatic cancer suggest a prognostic role for α-smooth muscle actin ({alpha}-SMA) expression and stromal density in the peritumoural stroma. The aim of this study was to further validate the impact of {alpha}-SMA expression and stromal density in resectable pancreatic cancer patients treated with adjuvant gemcitabine compared with untreated patients. Methods: CONKO-001 was a prospective randomised phase III study investigating the role of adjuvant gemcitabine as compared with observation. Tissue samples of 162 patients were available for immunohistochemistry on tissue microarrays to evaluate the impact of {alpha}-SMA expression and stromal density impact on patient outcome. Results: High {alpha}-SMA expression in tumour stroma was associated with worse patient outcome (DFS: P=0.05, OS: P=0.047). A dense stroma reaction was associated with improved disease-free survival (DFS) and overall survival (OS) in the overall study population (DFS: P=0.001, OS: P=0.001). This positive prognostic impact was restricted to patients with no adjuvant treatment (DFS: P<0.001, OS: P<0.001). In multivariable analysis, {alpha}-SMA and stromal density expression were independently predictive factors for survival. Conclusions: Our data confirm the negative prognostic impact of high α-SMA expression in pancreatic cancer patients after curatively intended resection. In contrast to former investigations, we found a positive prognostic impact for a dense stroma. This significant influence was restricted to patients who received no adjuvant therapy

Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study

BACKGROUND: Long-term survival (LTS) in patients (pts) with pancreatic cancer is still uncommon, little data is available to identify long-term survivors. The CONKO-001 study, which established gemcitabine after resection as adjuvant therapy, may provide data to answer this question. METHODS: CONKO-001 pts with an overall survival >/=5 years were compared to those who survived /=5 years were identified. It was possible to obtain tumor specimens of 39 pts (72%). Histological re-evaluation confirmed adenocarcinoma in 38 pts, 1 showed a high-grade neuroendocrine tumor. Univariate analysis for all 53 LTS pts with adenocarcinoma compared to the remaining 300 non-LTS pts revealed as relevant active treatment, tumor grading, tumor size, lymph nodes. No significance could be demonstrated for resection margin, sex, age, Karnofsky performance status, CA 19-9 at study entry. In multivariate analysis, tumor grading, active treatment, tumor size, lymph node involvement were independent prognostic factors for LTS. CONCLUSION: Long-term survival can be achieved in adenocarcinoma of the pancreas