Inoperable Pancreatic Cancer Research Articles

PO-1912: Clinical experience of using stereotactic ablative body radiotherapy on inoperable pancreatic cancer

PO-1912: Clinical experience of using stereotactic ablative body radiotherapy on inoperable pancreatic cancer

Impact on prognosis of early weight loss during palliative chemotherapy in patients diagnosed with advanced pancreatic cancer

AimWeight loss at diagnosis is common in pancreatic cancer (PC) and can adversely affect overall survival (OS). Little is known about the impact of weight loss occurring during palliative treatment. This study aimed to investigate if early weight loss during chemotherapy for inoperable PC affects OS. MethodThis retrospective study included patients newly-diagnosed with inoperable PC. Consecutive patients initiating first-line palliative chemotherapy between Jan’15 – Jan’19 with data on percentage weight loss at week 4 of treatment (%WLWeek4) were eligible. %WLWeek4 was dichotomised using 5% cut-off. OS was measured from chemotherapy initiation. Survival analysis was performed using Cox regression. ResultsEligible patients (n = 255); 59.2% with head/neck PC; 52.6% metastatic; received triplet (32.2%), doublet (42.7%) or single-agent (25.1%) palliative chemotherapy. Median %WLWeek4 was −2.05% (95% confidence interval (CI) −2.58 to −1.56); %WLWeek4 was ≥5% in 23.1% patients.Patients on triplet chemotherapy were more likely to develop %WLWeek4 of ≥5% [35.4% (triplet) vs. 19.3% (doublet) vs 14.1% (monotherapy); multivariable Odds Ratio (triplet vs monotherapy) =3.25; 95% CI 1.40-7.56; p-value 0.006].Median OS was 9.7 months (95% CI 8.54–10.41). Multivariable Cox regression demonstrated shorter OS if %WLWeek4 ≥5% (median OS 7.4 months (95% CI 6.27–10.01) vs. 9.9 months (95% CI 9.20–12.05); HR 2.37 (95% CI 1.64–3.42), P < 0.001); this was independent from other factors (stage, age, number of chemotherapy drugs, ECOG-PS), including response to therapy (supporting that %WLWeek4 impacted on OS regardless of response to therapy). ConclusionIn advanced PC treated with palliative chemotherapy, a %WLWeek4 ≥5% was more prevalent in patients undergoing triplet chemotherapy, and was associated with shorter OS, regardless of response/progression to therapy. Early identification and intervention of weight loss seems to be key to improve patient outcomes.

R0 resection following chemo (radio)therapy improves survival of primary inoperable pancreatic cancer patients. Interim results of the German randomized CONKO-007\xb1 trial

PurposeChemotherapy with or without radiotherapy is the standard in patients with initially nonmetastatic unresectable pancreatic cancer. Additional surgery is in discussion. The CONKO-007 multicenter randomized trial examines the value of radiotherapy. Our interim analysis showed a significant effect of surgery, which may be relevant to clinical practice.MethodsOne hundred eighty patients received induction chemotherapy (gemcitabine or FOLFIRINOX). Patients without tumor progression were randomized to either chemotherapy alone or to concurrent chemoradiotherapy. At the end of therapy, a panel of five independent pancreatic surgeons judged the resectability of the tumor.ResultsFollowing induction chemotherapy, 126/180 patients (70.0%) were randomized to further treatment. Following study treatment, 36/126 patients (28.5%) underwent surgery; (R0: 25/126 [19.8%]; R1/R2/Rx [n = 11/126; 6.1%]). Disease-free survival (DFS) and overall survival (OS) were significantly better for patients with R0 resected tumors (median DFS and OS: 16.6 months and 26.5 months, respectively) than for nonoperated patients (median DFS and OS: 11.9 months and 16.5 months, respectively; p = 0.003). In the 25 patients with R0 resected tumors before treatment, only 6/113 (5.3%) of the recommendations of the panel surgeons recommended R0 resectability, compared with 17/48 (35.4%) after treatment (p < 0.001).ConclusionTumor resectability of pancreatic cancer staged as unresectable at primary diagnosis should be reassessed after neoadjuvant treatment. The patient should undergo surgery if a resectability is reached, as this significantly improves their prognosis.

Ablative Five-Fraction Stereotactic Body Radiation Therapy for Inoperable Pancreatic Cancer Using Online MR-Guided Adaptation

PurposePatients with inoperable pancreatic adenocarcinoma have limited options, with traditional chemoradiation providing modest clinical benefit and an otherwise poor prognosis. Stereotactic body radiation therapy for pancreatic cancer is limited by proximity to organs-at-risk (OAR). However, stereotactic magnetic resonance-guided adaptive radiation therapy (SMART) has shown promise in delivering ablative doses safely. We sought to demonstrate the benefits of SMART using a 5-fraction approach with daily on-table adaptation. Methods and MaterialsPatients with locally advanced, nonmetastatic pancreatic adenocarcinoma were treated with 50 Gy in 5 fractions (biologically effective dose10 100 Gy) with a prescribed goal of 95% planning target volume coverage by 95% of prescription, prioritizing hard OAR constraints. Daily online adaptation was performed using magnetic resonance-guidance and on-table reoptimization. Patient outcomes, treatment factors, and daily adaptation were evaluated. ResultsForty-four patients were treated with SMART at our institution from 2014 to 2019. Median follow-up from date of diagnosis was 16 months (range, 6.7-51.6). Late toxicity was limited to 2 (4.6%) grade 3 (gastrointestinal ulcers) and 3 (6.8%) grade 2 toxicities (duodenal perforation, antral ulcer, and gastric bleed). Tumor abutted OARs in 35 patients (79.5%) and tumor invaded OARs in 5 patients (11.1%). Reoptimization was performed for 93% of all fractions. Median overall survival was 15.7 months (95% confidence interval, 10.2-21.2), while 1-year and 2-year overall survival rates were 68.2% and 37.9%, respectively. One-year local control was 84.3%. ConclusionsThis is the first reported experience using 50 Gy in 5 fractions for inoperable pancreatic cancer. SMART allows this ablative dose with promising outcomes while minimizing toxicity. Additional prospective trials evaluating efficacy and safety are warranted.

An observational study to justify and plan a future phase III randomized controlled trial of metformin in improving overall survival in patients with inoperable pancreatic cancer without liver metastases.

Metformin has plausible direct and indirect anti-cancer properties against pancreatic adenocarcinoma cells. However, metformin may only be efficacious in patients with inoperable pancreatic ductal adenocarcinoma (PDAC) without liver metastases. Absorption may be decreased by gastrointestinal symptoms and proton pump inhibitors (PPIs). We aimed to justify and inform a future phase III trial of metformin versus placebo on survival in inoperable PDAC by documenting prevalence of patients meeting eligibility criteria, gastrointestinal symptoms and PPI use. Patient notes with PDAC were reviewed at a large teaching hospital over 2years. Study variables were obtained from multiple sources of information. 141 participants were identified (51.8% female), of which 37.6% were not prescribed metformin at diagnosis and had no radiological hepatic metastases. Characteristics were similar between non-metformin and metformin users. In eligible patients, 65.2% reported nausea and vomiting and 46.2% were prescribed PPIs. Approximately, a third of all patients with inoperable PDAC are eligible for a future trial of metformin, allowing an estimate of the number of hospitals required for recruitment. Nausea and vomiting are common and should be managed effectively to prevent trial dropouts. PPI use is frequent and their influence on metformin's pharmacodynamic actions needs to be clarified.

Stereotactic MR-guided on-table adaptive radiation therapy (SMART) for locally advanced pancreatic cancer.

TPS786 Background: Standard dose radiation therapy has been unsuccessful in inoperable pancreatic cancer; with a negative study (LAP07) for conventional chemoradiation and dropping of the stereotactic body radiation therapy arm in Alliance A021501. Recently, reports of using high dose ablative radiation therapy has been associated with increased survival in retrospective studies. Moreover, technological advances with MRI-guided radiation therapy offer improved targeting and the ability to change the radiation delivery on a daily fashion; allowing ablative radiation doses over one week. However, it is not clear whether this can be done safely on a multiinstitutional basis. Methods: We are conducting the largest prospective study of ablative radiation therapy in pancreatic cancer. The study is a single arm, multi-institutional phase II, industry sponsored study to investigate the safety and efficacy of Stereotactic, MR guided, on-table-Adaptive Radiation Therapy (SMART). Eligibility criteria include locally advanced and borderline resectable pancreatic cancer patients with ECOG PS of 0 or 1; who have non-metastatic disease after a minimum of 3 months of any systemic therapy; including investigational agents. Patients will receive MR-guided radiation therapy to a dose of 50 Gy / 5 fractions; with maximum tumor coverage delivered each fraction that allows keeping the gastrointestinal organs at risk to a dose of 33 Gy or less. Primary endpoint is grade 3 of higher gastrointestinal toxicity at 90 days. Secondary endpoints are overall survival at 2 years, distant progression free survival at 6 months, and changes in patient related quality of life at 3 and 12 months. Target sample size was calculated to show at a significance level 0.05, a reduction of the toxicity rate to 8% or lower by using SMART compared with 15.8%, the toxicity rate of conventionally delivered chemoradiation at a power level 0.8. Given an expected 15% drop-out, the enrollment goal is 133. Descriptive statistics will be used for secondary objectives. The study opened in January, 2019 and is currently opened at 4 centers; with other US and international sites pending. Sponsored by Viewray, Inc. Clinical trial information: NCT03621644.

High-intensity focused ultrasound therapy as part of combined treatment for inoperable pancreatic cancer

High-intensity focused ultrasound therapy as part of combined treatment for inoperable pancreatic cancer

The clinical and cost-effectiveness of supplemental parenteral nutrition in oncology

BackgroundClinical guidelines recommend that parenteral nutrition (PN) is added to enteral nutrition (EN; supplemental parenteral nutrition (SPN)) in order to meet energy and protein needs in patients with cancer when EN alone is insufficient. However, although cancer-related malnutrition is common, there is poor awareness of the value of nutritional care, resulting in SPN being chronically underused.MethodsWe performed a targeted literature review and exploratory cost-utility analysis to gather evidence on the clinical effectiveness of SPN, and to estimate the potential cost-effectiveness of SPN versus EN alone in an example cancer setting.ResultsThe literature review identified studies linking SPN with malnutrition markers, and studies linking malnutrition markers with clinical outcomes. SPN was linked to improvements in body mass index (BMI), fat-free mass, phase angle (PhA) and prealbumin. Of these markers, BMI and PhA were strong predictors of survival. By combining published data, we generated indirect estimates of the overall survival HR associated with SPN; these ranged from 0.80 to 0.99 (mode 0.87). In patients with Stage IV inoperable pancreatic cancer, the incremental cost-effectiveness ratio versus EN alone was estimated to be £41 350 or £91 501 depending on whether nursing and home delivery costs for EN and SPN were combined or provided separately.ConclusionDespite a lack of direct evidence, the results of the literature review demonstrate that SPN may provide important clinical and quality of life benefits to patients with cancer. The potential for any improvement in outcomes in the modelled patient population is very limited, so cost-effectiveness may be greater in patients with less severe disease and other types of cancer.

Ablative Re-irradiation of Inoperable Pancreatic Cancer: A Case Study of Gastrointestinal Sparing through MR-guided Online Adaptive Radiotherapy

Ablative Re-irradiation of Inoperable Pancreatic Cancer: A Case Study of Gastrointestinal Sparing through MR-guided Online Adaptive Radiotherapy

Deterioration in Muscle Mass and Physical Function Differs According to Weight Loss History in Cancer Cachexia.

Background: Muscle mass and physical function (PF) are common co-primary endpoints in cancer cachexia trials, but there is a lack of data on how these outcomes interact over time. The aim of this secondary analysis of data from a trial investigating multimodal intervention for cancer cachexia (ClinicalTrials.gov: NCT01419145) is to explore whether changes in muscle mass and PF are associated with weight loss and cachexia status at baseline. Methods: Secondary analysis was conducted using data from a phase II randomized controlled trial including 46 patients with stage III–IV non-small cell lung cancer (n = 26) or inoperable pancreatic cancer (n = 20) due to commence chemotherapy. Cachexia status at baseline was classified according to international consensus. Muscle mass (assessed using computed tomography (CT)) and PF outcomes, i.e., Karnofsky performance status (KPS), self-reported PF (self-PF), handgrip strength (HGS), 6-minute walk test (6MWT), and physical activity (PA), were measured at baseline and after six weeks. Results: When compared according to cachexia status at baseline, patients with no/pre-cachexia had a mean loss of muscle mass (−5.3 cm2, p = 0.020) but no statistically significant change in PF outcomes. Patients with cachexia also lost muscle mass but to a lesser extent (−2.8 cm2, p = 0.146), but demonstrated a statistically significant decline in PF; KPS (−3.8 points, p = 0.030), self-PF (−8.8 points, p = 0.027), and HGS (−2.7 kg, p = 0.026). Conclusions: Weight loss history and cachexia status at baseline are of importance if one aims to detect changes in PF outcomes in cancer cachexia trials. To improve the use of co-primary endpoints that include PF in future trials, outcomes that have the potential to detect change relative to weight loss should be investigated further.

Endoscopic Ultrasound-guided Celiac Plexus Neurolysis to Alleviate Intractable Pain Caused by Advanced Pancreatic Cancer.

This study aimed to analyze the clinical safety and effectiveness of endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in alleviating intractable abdominal pain caused by advanced pancreatic cancer. A total of 58 patients with inoperable pancreatic cancer who underwent EUS-CPN from May 2015 to December 2017 were enrolled. Pain levels before and after EUS-CPN were assessed and compared using the Visual Analogue Scale. The preoperative Visual Analogue Scale score was 8.2±2.3, which decreased significantly to 3.6±1.5 at 2 days after EUS-CPN and to 2.2±0.8 after 1 month. The response rate was 79.3%. No patient experienced serious complications; 14 patients experienced mild, transient side effects (self-limiting diarrhea, reflex hypotension, and worsening of abdominal pain) that resolved within 48 hours. For pancreatic cancer patients, EUS-CPN can effectively control pain with minimal adverse effects.

Meta-analysis of the clinical efficacy of FOLFIRINOX in the treatment of inoperable advanced pancreatic cancer and gemcitabine-based regimen

Meta-analysis of the clinical efficacy of FOLFIRINOX in the treatment of inoperable advanced pancreatic cancer and gemcitabine-based regimen

Survival and Safety of Patients with Inoperable Pancreatic Cancer in Clinical Trials That Haven’t Demonstrated Increase of Overall Survival

All randomized clinical trials in oncology, where the use of new medicines results in an increase in patient life expectancy, improvement of their quality of life, or at least improvement...

Plasma ctDNA RAS mutation analysis by digital polymerase chain reaction in patients with inoperable pancreatic cancer

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis and high mortality worldwide. Despite the emergence of new therapeutic approaches for the treatment of inoperable PDAC, reliable prognostic/predictive biomarkers are lacking. PDAC harbours mutations in the KRAS gene in 80-90% of patients. The aim of the present study is the detection and quantification of RAS mutations in the ctDNA of patients with inoperable PDAC by BEAMing digital polymerase chain reaction (PCR), in order to (a) evaluate the correlation with tissue RAS mutation status in the tumour, (b) study the baseline prognostic significance and (c) study the predictive significance of ctDNA RAS mutation kinetics for the prediction of response to systemic/neoadjuvant therapy. Methods Plasma samples of patients with locally advanced or metastatic inoperable PDAC were collected at diagnosis and at 4-6 weeks after treatment initiation and were tested for 34 mutations in the KRAS and NRAS genes by BEAMing digital polymerase chain reaction (PCR). This method has a particularly high sensitivity and can accurately quantify mutated DNA as the Mutant Allele Fraction (MAF). To test the efficacy and validity of ctDNA for the detection of RAS mutations, RAS mutations will also be tested for on paired tumour tissue samples of the patients under study by PCR. Results So far, 38 plasma samples from 20 patients were available for analysis. At baseline, mutant ctDNA pertaining to exon 2 codon 12 of the KRAS gene was detected in all patients’ samples and, additionally, to exon 3 codon 61 of the NRAS gene in one of them. Comparison of plasma and tissue results revealed a high agreement of the RAS mutational profile in plasma ctDNA and tissue tumour DNA. Kinetics of the RAS mutational load during therapy and its prognostic or predictive value will be analysed with further cohort expansion. Conclusions This work highlights the potential role of liquid biopsies in the management of PDAC and, more specifically, will yield preliminary data on the role of RAS ctDNA profiling as a predictive and prognostic marker. Legal entity responsible for the study Department of Medical Oncology, University General Hospital of Ioannina. Funding Hellenic Society of Medical Oncology (HeSMO) and Society for Study of Clonal Heterogeneity of Neoplasia (EMEKEN). Disclosure G. Pentheroudakis: Research grant / Funding (institution), Support material was provided for this project: Sysmex Inostics. All other authors have declared no conflicts of interest.

CA 19-9 Maintains Prognostic Value for Inoperable Pancreatic Cancer Patients Receiving Definitive Hypofractionated or Stereotactic Body Radiation Therapy

Use of carbohydrate antigen 19-9 (CA 19-9) in patients with resectable pancreatic cancer is well-established. The role of CA 19-9 in management of patients with inoperable pancreatic cancer receiving treatment with definitive hypofractionated or stereotactic body radiation therapy (SBRT) is less clear. Eligible patients for this IRB approved retrospective study included patients diagnosed with inoperable pancreatic cancer who received a definitive course of radiation therapy (RT) in either 50 – 52 Gy in 5 fractions or 50.7 – 67.5 Gy in 15 fractions. Patients were also required to have a recorded CA 19-9 value at diagnosis. Available CA 19-9 values were also recorded prior to radiation (within one month) and after RT (within 3 months). CA 19-9 levels were adjusted for bilirubin >2 mg/dL by dividing CA 19-9 level by bilirubin level. Overall survival (OS) was calculated from start date of RT. Patients were grouped based on CA 19-9 cutoff value of 90 U/mL (derived from literature). Kaplan-Meier curves were generated and differences between groups were determined using the log-rank method. Fisher’s Exact testing was performed to test correlation between CA 19-9 levels and likelihood of receiving a pancreatectomy. A total of 55 patients were eligible for this study (40 patients with locally advanced disease, 10 patients with borderline-resectable disease, and 5 patients who were medically inoperable). Median follow up was 13 months. Treatments included 5 fraction SBRT (n=15) or 15 fraction hypofractionated regimen (n=40). CA 19-9 levels were available for 51 patients prior to RT and 50 patients after RT. Median CA 19-9 levels were 121 U/mL (range: 1 – 9674) at diagnosis, 50 U/mL (1 – 29690) prior to RT, and 43 U/mL (1 – 28925) after RT. OS at 1 year was significantly improved with CA 19-9 level ≤ 90 U/mL at diagnosis (75% vs 59%, P=0.04), before RT (73% vs 48%, P=0.04), and within 3 months after RT (83% vs 25%, P<0.01). Fisher’s Exact testing did not identify significant correlation between likelihood of pancreatectomy and CA 19-9 levels at diagnosis (P=0.75), before (P=1.00) or after (P=0.46) RT (analysis excluded medically inoperable cases). CA 19-9 demonstrated a role as a prognostic marker for patients with inoperable pancreatic cancer receiving definitive hypofractionated/SBRT courses. CA 19-9 values do not appear to impact likelihood of undergoing a pancreatectomy after RT.

Outcomes of enteral metallic stent in patients with pancreatic carcinoma and gastric outlet obstruction: A single center experience

Duodenal obstruction is uncommon in patients with pancreatic cancer. However, the obstruction rate is increasing as a result of advancements in chemotherapy and target therapy. This study aimed to investigate the effect of self-expandable metal stent placement on outcomes of patients with duodenal obstruction secondary to pancreatic carcinoma. Twenty-nine consecutive inoperable patients with pancreatic cancer and gastric outlet obstruction who received metallic stent placement in our hospital between September 2009 and October 2017 were enrolled for analysis. Fifteen male patients and 14 female patients receiving stent placement with a median age of 68 years (range, 50-85 years) were included. The technical and clinical success rates of the procedure were 100% and 89.7%, respectively. The Gastric Outlet Obstruction Scoring System scores were significantly improved at day 1 (1.14±0.51) and days 7 (2.21±0.9) after the implantation compared to those prior to the procedure (0.38±0.49) (p<0.001). Aspiration pneumonia and bleeding developed in 1 patient (3.4%) after the procedure. Stent dysfunction developed in 6 of 29 patients (20.6%). The median stent patency time was 109 days (range, 10-314 days). The median survival time was 114 days (range, 15-323 days). Post-stent chemotherapy predicted better survival (hazard ratio: 0.2, 95% confidence interval: 0.08-0.51, p=0.001). Metallic stent placement is an effective treatment for patients with inoperable pancreatic cancer leading to gastric outlet obstruction. Chemotherapy may be considered following stent placement.

Sustained co-delivery of gemcitabine and cis-platinum via biodegradable thermo-sensitive hydrogel for synergistic combination therapy of pancreatic cancer

Pancreatic cancer is one of the most devastating cancers with poor prognosis and no significant change in the survival rate over the past decades. Localized targeted drug delivery through interventional endoscopic ultrasonography-guided fine-needle injection (EUS-FNI) is an attractive and minimally invasive strategy for inoperable pancreatic cancer. An injectable in-situ formed long-lasting drug delivery system is a promising alternative for the localized treatment of pancreatic cancer via EUS-FNI. Here, a biodegradable thermo-sensitive copolymer hydrogel for the co-delivery of anticancer agents gemcitabine (GEM) and cis-platinum (DDP) was developed. This hydrogel is a free flowable liquid at room temperature that changes into a semi-solid hydrogel following injection in response to the physiological temperature. Both in vitro and in vivo drug release behaviors indicate sustained drug release of this delivery system. Synergistic cellular proliferation inhibition and desirable apoptosis promotion have been found when pancreatic cancer Bxpc-3 cells were co-cultured with this GEM-DDP/hydrogel system. After a single intratumoral injection, the dual-drug loaded hydrogel formulation exhibited superior anti-tumor efficacy and minimized systemic side effect on pancreatic cancer xenograft mouse model in comparison to the intravenously injected free GEM and DDP combination. In addition, a strong synergistic therapeutic effect of the GEM-DDP/hydrogel system against pancreatic cancer has been found in vitro and in vivo compared to the single-drug loaded hydrogel composites. The obtained findings suggest this developed thermo-sensitive copolymer hydrogel system as a potential universal carrier for the localized targeted delivery of multi-drugs, for use in a variety of inoperable solid tumors.

A double-blind randomized comparative clinical trial to evaluate the safety and efficacy of dendritic cell vaccine loaded with WT1 peptides (TLP0-001) in combination with S-1 in patients with advanced pancreatic cancer refractory to standard chemotherapy

BackgroundPancreatic cancer is a refractory malignancy, and the development of a new effective treatment strategy is needed. We generated a dendritic cell vaccine by culturing monocytes obtained by apheresis of blood from each patient, inducing their differentiation into dendritic cells, and pulsing with tumor antigen peptides. However, the clinical efficacy of the vaccine has not been established. We therefore decided to conduct an exploratory clinical trial of dendritic cell vaccine loaded with Wilms’ tumor gene 1 peptides (TLP0-001) as a potential new treatment for patients with advanced pancreatic cancer refractory to standard chemotherapy.MethodsThis is an investigator-initiated, double-blind, comparative trial. The patients were allocated to two groups in a 1:1 ratio through a central registration by dynamic allocation. A total of 185 patients with inoperable or metastatic pancreatic cancer who were refractory or intolerant to standard primary chemotherapy with gemcitabine plus nab-paclitaxel will be allocated to secondary treatment either with placebo in combination with S-1 (the control group) or TLP0-001 in combination with S-1 (the investigational product group). The primary objective of this trial is to evaluate the safety and efficacy (as measured by overall survival) of the investigational product by comparing the two groups. This clinical trial will be performed in accordance with Japanese Good Clinical Practice guidelines.DiscussionClinical trials of the standard regimen, including gemcitabine, for advanced pancreatic cancer are ongoing worldwide. However, a strategy for after the primary treatment has not been established. We therefore decided to conduct this study to evaluate the safety and efficacy of TLP0-001 as a secondary treatment for pancreatic cancer in anticipation of the approval of this new drug in Japan. This trial is conducted with full consideration of safety, as it is the first-in-human clinical trial of TLP0-001; thus, the trial will be conducted only at the Second Department of Surgery at Wakayama Medical University until the safety is confirmed by interim analysis. We plan to conduct a multicenter trial at 18 institutions in Japan after confirmation of the safety.Trial registrationUniversity Hospital Medical Information Network Clinical Trials Registry, UMIN000027179. Registered on 9 April 2017.

Using adaptive magnetic resonance image-guided radiation therapy for treatment of inoperable pancreatic cancer.

BackgroundAdaptive magnetic resonance imaging‐guided radiation therapy (MRgRT) can escalate dose to tumors while minimizing dose to normal tissue. We evaluated outcomes of inoperable pancreatic cancer patients treated using MRgRT with and without dose escalation.MethodsWe reviewed 44 patients with inoperable pancreatic cancer treated with MRgRT. Treatments included conventional fractionation, hypofractionation, and stereotactic body radiation therapy. Patients were stratified into high‐dose (biologically effective dose [BED10] >70) and standard‐dose groups (BED10 ≤70). Overall survival (OS), freedom from local failure (FFLF) and freedom from distant failure (FFDF) were evaluated using Kaplan‐Meier method. Cox regression was performed to identify predictors of OS. Acute gastrointestinal (GI) toxicity was assessed for 6 weeks after completion of RT.ResultsMedian follow‐up was 17 months. High‐dose patients (n = 24, 55%) had statistically significant improvement in 2‐year OS (49% vs 30%, P = 0.03) and trended towards significance for 2‐year FFLF (77% vs 57%, P = 0.15) compared to standard‐dose patients (n = 20, 45%). FFDF at 18 months in high‐dose vs standard‐dose groups was 24% vs 48%, respectively (P = 0.92). High‐dose radiation (HR: 0.44; 95% confidence interval [CI]: 0.21‐0.94; P = 0.03) and duration of induction chemotherapy (HR: 0.84; 95% CI: 0.72‐0.98; P = 0.03) were significantly correlated with OS on univariate analysis but neither factor was independently predictive on multivariate analysis. Grade 3+ GI toxicity occurred in three patients in the standard‐dose group and did not occur in the high‐dose group.ConclusionsPatients treated with dose‐escalated MRgRT demonstrated improved OS. Prospective evaluation of high‐dose RT regimens with standardized treatment parameters in inoperable pancreatic cancer patients is warranted.

Mistletoe therapy in primary and recurrent inoperable pancreatic cancer. A phase III prospective, randomized, double-blinded, multicenter, parallel group, placebo-controlled clinical trial on overall survival and health-related quality of life (MISTRAL)

Mistletoe therapy in primary and recurrent inoperable pancreatic cancer. A phase III prospective, randomized, double-blinded, multicenter, parallel group, placebo-controlled clinical trial on overall survival and health-related quality of life (MISTRAL)