Small beams, fast predictions: a comparison of machine learning dose prediction models for proton minibeam therapy.

BACKGROUND: Dose calculations for novel radiotherapy cancer treatments such as proton minibeam radiation therapy is often done using full Monte Carlo (MC) simulations. As MC simulations can be very time consuming for this kind of application, deep learning models have been considered to accelerate dose estimation in cancer patients. PURPOSE: This work systematically evaluates the dose prediction accuracy, speed and generalization performance of three selected state-of-the-art deep learning models for dose prediction applied to the proton minibeam therapy. The strengths and weaknesses of those models are thoroughly investigated, helping other researchers to decide on a viable algorithm for their own application. METHODS: The following recently published models are compared: first, a 3D U-Net model trained as a regression network, second, a 3D U-Net trained as a generator of a generative adversarial network (GAN) and third, a dose transformer model which interprets the dose prediction as a sequence translation task. These models are trained to emulate the result of MC simulations. The dose depositions of a proton minibeam with a diameter of 800µm and an energy of 20-100 MeV inside a simple head phantom calculated by full Geant4 MC simulations are used as a case study for this comparison. The spatial resolution is 0.5 mm. Special attention is put on the evaluation of the generalization performance of the investigated models. RESULTS: Dose predictions with all models are produced in the order of a second on a GPU, the 3D U-Net models being fastest with an average of 130 ms. An investigated 3D U-Net regression model is found to show the strongest performance with overall 61.0 % ± $\%\pm$ 0.5% of all voxels exhibiting a deviation in energy deposition prediction of less than 3% compared to full MC simulations with no spatial deviation allowed. The 3D U-Net models are observed to show better generalization performance for target geometry variations, while the transformer-based model shows better generalization with regard to the proton energy. CONCLUSIONS: This paper reveals that (1) all studied deep learning models are significantly faster than non-machine learning approaches predicting the dose in the order of seconds compared to hours for MC, (2) all models provide reasonable accuracy, and (3) the regression-trained 3D U-Net provides the most accurate predictions.

[Overview of relevant clinical recommendations from the new S3 guidelines on acute and chronic pancreatitis]. / Überblick über relevante klinische Empfehlungen aus der neuen S3-Leitlinie "Akute und chronische Pankreatitis".

Acute pancreatitis is a primary sterile inflammation of the pancreas, which is characterized by an unphysiological enzyme activation. This leads to an inflammatory reaction with edema, vascular damage and cell decay. The first German interdisciplinary S3 guidelines on chronic pancreatitis were published in 2012. Under the auspices of the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and with the participation of various societies and patient representatives, the guidelines were recently revised and extended, Comprehensive S3 guidelines on acute and chronic pancreatitis were compiled and agreed by consensus. This article presents the important clinical aspects on acute pancreatitis from these guidelines in a compact form and the recommendations are justified.

The importance of sentinel lymph node biopsy following neoadjuvant chemotherapy in patients with breast cancer: prospective multicentre trial.

INTRODUCTION: The role of sentinel lymph node biopsy (SLNB) in patients with breast cancer after neoadjuvant chemotherapy (NAC) is currently under discussion. The aim of our study was to determine the false negativity rate (FNR) of SLNB, the accuracy of ultrasound examination in the evaluation of the status of lymph nodes and the accuracy of perioperative cryobiopsy of the sentinel lymph node (SLN). METHODS: Prospective multicentre study, which took place in years 20182020 at three centres in the Czech Republic. A total of 59 patients were evaluated. RESULTS: The FNR of SLNB in the group of patients with cN1 before NAC and ycN0 after NAC was 12.5%. The FNR of perioperative histological examination of the SLN was 38.5%. The FNR of ultrasound examination of axillary lymph nodes in patients after NAC was 35.5%, and the false positivity rate was 16.7%. The incidence of inflammatory complications in our cohort was 3.3%. CONCLUSION: The FNR of SLNB in the group of patients with cN1 before NAC and ycN0 after NAC exceeds the tolerable limit of 10%. The FNR of perioperative histological examination of the SLN is high; definitive histological examination of the SLN may change the original diagnostic-therapeutic plan. Ultrasound examination of the axillary lymph nodes in patients after NAC is a method with high false negativity and positivity and may not correspond with the perioperative finding. The incidence of inflammatory complications in our cohort in patients after NAC is comparable to literature data on the frequency of complications in patients without NAC.

Study of the X-ray radiation interaction with a multislit collimator for the creation of microbeams in radiation therapy.

Microbeam radiation therapy (MRT) is a developing radiotherapy, based on the use of beams only a few tens of micrometres wide, generated by synchrotron X-ray sources. The spatial fractionation of the homogeneous beam into an array of microbeams is possible using a multislit collimator (MSC), i.e. a machined metal block with regular apertures. Dosimetry in MRT is challenging and previous works still show differences between calculated and experimental dose profiles of 10-30%, which are not acceptable for a clinical implementation of treatment. The interaction of the X-rays with the MSC may contribute to the observed discrepancies; the present study therefore investigates the dose contribution due to radiation interaction with the MSC inner walls and radiation leakage of the MSC. Dose distributions inside a water-equivalent phantom were evaluated for different field sizes and three typical spectra used for MRT studies at the European Synchrotron Biomedical beamline ID17. Film dosimetry was utilized to determine the contribution of radiation interaction with the MSC inner walls; Monte Carlo simulations were implemented to calculate the radiation leakage contribution. Both factors turned out to be relevant for the dose deposition, especially for small fields. Photons interacting with the MSC walls may bring up to 16% more dose in the valley regions, between the microbeams. Depending on the chosen spectrum, the radiation leakage close to the phantom surface can contribute up to 50% of the valley dose for a 5 mm × 5 mm field. The current study underlines that a detailed characterization of the MSC must be performed systematically and accurate MRT dosimetry protocols must include the contribution of radiation leakage and radiation interaction with the MSC in order to avoid significant errors in the dose evaluation at the micrometric scale.

[Surgical procedures for the correction and stabilization of pes planovalgus]. / Stabilisierung und Korrektur der medialen Säule im Rahmen der operativen Pes-planovalgus-Therapie.

The medial column of the foot is a relevant factor of the pathogenesis of pes planovalgus. Crucial anatomic structures are the tibiocalcaneonavicular ligament complex, the naviculocuneiform joints, including the ossa cuneiformia, and the first tarsometatarsal joint. A combination of bony and soft tissue reconstructive techniques must, therefore, be taken into account when treating pes planovalgus. The present article presents stabilizing and correcting surgical procedures for the medial column of the foot, including basic anatomy and biomechanics.

BrachyView: development of an algorithm for real-time automatic LDR brachytherapy seed detection.

BrachyView is a novel in-body imaging system developed to provide real-time intraoperative dosimetry for low dose rate prostate brachytherapy treatments. Seed positions can be reconstructed after in-vivo implantation using a high-resolution pinhole gamma camera inserted into the patient rectum. The obtained data is a set of 2D projections of the seeds on the image plane. The 3D reconstruction algorithm requires the identification of the seed's centre of mass. This work presents the development and techniques adopted to build an algorithm that provides the means for fully automatic seed centre of mass identification and 3D position reconstruction for real-time applications. The algorithm presented uses a local feature detector, speeded up robust features, to perform detection of brachytherapy seed 2D projections from images, allowing for robust seed identification. Initial results have been obtained with datasets of 30, 96 and 98 I-125 brachytherapy seeds implanted into a prostate gel phantom. It can detect 97% of seeds and correctly match 97% of seeds. The average overall computation time of 2.75 s per image and improved reconstruction accuracy of 22.87% for the 98 seed dataset was noted. Elimination processes for initial false positive detection removal have shown to be extremely effective, resulting in a 99.9% reduction of false positives, and when paired with automatic frame alignment and subtraction procedures allows for the effective removal of excess counts generated by previously implanted needles. The proposed algorithm will allow the BrachyView system to be used as a real-time intraoperative dosimetry tool for low dose rate prostate brachytherapy treatments.

Harmonic scalpel versus traditional ligation in axillary dissection for breast cancer: a retrospective multivariate analysis.

INTRODUCTION: The aim of this pilot retrospective study is to evaluate the complication rate in patients after axillary dissection comparing preparation with harmonic scalpel vs traditional ligation technique, and to analyse risk factors for complications occurrence. METHODS: 144 patients with 148 axillary dissections operated in a single centre between January 2014 and 2019 were included into the study. Axillary dissection was performed using harmonic scalpel in 73 and absorbable ligations in 70 cases. RESULTS: Seroma formation was observed in 41 patients (56.2%) in the harmonic scalpel group and in 21 patients (30.0%) in the ligations group (p=0.003). The mean period from the surgery to drain removal was 4.0 days in the harmonic scalpel group and 3.0 days in the ligations group (p<0.001). The mean amount of the drained fluid after mastectomy was 300.9 ml in the harmonic scalpel group and 168.7 ml in the ligations group (p=0.005); after breast conserving surgery, it was 241.9 ml and 107.4 ml, respectively (p =0.023). CONCLUSION: In comparison with traditional ligations with absorbable material, axillary dissection using harmonic scalpel significantly increases the risk of postoperative seroma formation, prolongs the time from the surgery to drain removal, and increases the amount of drained fluid.

Nylon sutures versus skin staples in foot and ankle surgery: is there a clinical difference?

BACKGROUND: Staple sutures have already been proven as a good alternative to nylon sutures for wound closure in hip and knee surgeries. One such advantage to using staple sutures is the significant decrease in surgical time. In foot surgeries, staple sutures are still considered critical and are only used sporadically. OBJECTIVE: The aim of this retrospective study was to compare nylon sutures and skin staples for wound closure in foot and ankle surgeries with respect to complications and patient satisfaction. METHODS: A total of 61 patients underwent different operations in the fore-, mid-, and hindfoot areas, which were performed by a single surgeon. Twenty-nine patients received staple wound closures, while 32 patients received nylon suture closures using the Donati back-and-forth technique. Incision length, surgery time, in-patient stay, and wound complications were recorded. Furthermore, a patient survey using the verbal numeric rating scale (VNRS) for subjective pain and cosmetic results at the time of stitch removal (14 days) and after a 6-week follow-up was conducted. RESULTS: A significant between-group difference was found for surgery time (p = .041) and VNRS for pain (p < .001), with better results seen for staple sutures. Four patients with staple sutures and five with nylon sutures experienced wound dehiscence 14 days postoperatively. However, all patients had completely healed wounds at their 6-week follow-up. No revisional surgeries were necessary. CONCLUSION: The present results indicate that a skin staple wound closure is a considerable alternative to the nylon suture closure in foot and ankle surgeries. Nevertheless, further prospective randomized trials must cement these insights.

Validation of Geant4 for silicon microdosimetry in heavy ion therapy.

Microdosimetry is a particularly powerful method to estimate the relative biological effectiveness (RBE) of any mixed radiation field. This is particularly convenient for therapeutic heavy ion therapy (HIT) beams, referring to ions larger than protons, where the RBE of the beam can vary significantly along the Bragg curve. Additionally, due to the sharp dose gradients at the end of the Bragg peak (BP), or spread out BP, to make accurate measurements and estimations of the biological properties of a beam a high spatial resolution is required, less than a millimetre. This requirement makes silicon microdosimetry particularly attractive due to the thicknesses of the sensitive volumes commonly being ∼10 [Formula: see text]m or less. Monte Carlo (MC) codes are widely used to study the complex mixed HIT radiation field as well as to model the response of novel microdosimeter detectors when irradiated with HIT beams. Therefore it is essential to validate MC codes against experimental measurements. This work compares measurements performed with a silicon microdosimeter in mono-energetic [Formula: see text], [Formula: see text] and [Formula: see text] ion beams of therapeutic energies, against simulation results calculated with the Geant4 toolkit. Experimental and simulation results were compared in terms of microdosimetric spectra (dose lineal energy, [Formula: see text]), the dose mean lineal energy, y  D and the RBE10, as estimated by the microdosimetric kinetic model (MKM). Overall Geant4 showed reasonable agreement with experimental measurements. Before the distal edge of the BP, simulation and experiment agreed within ∼10% for y  D and ∼2% for RBE10. Downstream of the BP less agreement was observed between simulation and experiment, particularly for the [Formula: see text] and [Formula: see text] beams. Simulation results downstream of the BP had lower values of y  D and RBE10 compared to the experiment due to a higher contribution from lighter fragments compared to heavier fragments.

BrachyView: Reconstruction of seed positions and volume of an LDR prostate brachytherapy patient plan using a baseline subtraction algorithm.

PURPOSE: BrachyView is a novel in-body imaging system developed with the objective to provide real-time intraoperative dosimetry for low dose rate (LDR) prostate brachytherapy treatments. The BrachyView coordinates combined with conventional transrectal ultrasound (TRUS) imaging, provides the possibility to localise the effective position of the implanted seeds inside the prostate volume, providing a unique tool for intra-operative verification of the quality of the implantation. This research presents the first complete LDR brachytherapy plan reconstructed by the BrachyView system and is used to evaluate the effectiveness of an imaging algorithm with baseline subtraction. METHODS: A plan featuring 98 I-125 brachytherapy seeds, with an average activity of 0.248 mCi, were implanted into a prostate gel phantom under TRUS guidance. Images of implanted seeds were obtained by the BrachyView after the implantation of seeds. The baseline subtraction algorithm is applied as a pixel-to-pixel counts subtraction and is applied to every second projection obtained after the implantation of each needle. Seed positions and effectiveness of the baseline reconstruction in the identification of seeds were verified by a high-resolution post-implant CT scan. RESULTS: A complete brachytherapy plan has been reconstructed with a 100% detection rate. This is possible due to the effectiveness of the baseline subtraction, with its application an overall increase of 11.3% in position accuracy and 8.2% increase in detection rate was noted. CONCLUSION: It has been demonstrated that the BrachyView system shows the potential to be a solution to providing clinics with the means for intraoperative dosimetry for LDR prostate brachytherapy treatments.

Accuracy of ultrasonography in the assessment of liver fat compared with MRI.

AIM: To investigate the accuracy of ultrasonography in the assessment of hepatic steatosis using magnetic resonance imaging (MRI) as standard of reference and to explore the influence of additional hepatic iron overload. MATERIAL AND METHODS: A total of 2,783 volunteers (1,442 women, 1,341 men; mean age, 52.3±13.8 years) underwent confounder-corrected chemical-shift-encoded MRI of the liver at 1.5 T. Proton-density fat fraction (PDFF) and transverse relaxation rate (R2*) were calculated to estimate hepatic steatosis and liver iron overload, respectively. In addition, the presence of hepatic steatosis was assessed by B-mode ultrasonography. The sensitivity, specificity, and accuracy of hepatic ultrasonography were determined for different degrees of hepatic steatosis and different amounts of liver iron. RESULTS: MRI revealed hepatic steatosis in 40% of participants (n=1,112), which was mild in 68.9% (n=766), moderate in 26.7% (n=297), and severe in 4.4% (n=49) of patients. Ultrasonography detected hepatic steatosis in 37.8% (n=1,052), corresponding to 74.5% sensitivity and 86.6% specificity. The sensitivity of ultrasound increased with the amount of hepatic fat present and was 65.1%, 95%, and 96% for low, moderate, and high fat content; whereas the specificity was constantly high at 86.6%. The diagnostic accuracy of ultrasound for detection of hepatic steatosis did not vary significantly with the amount of liver iron present. CONCLUSION: Ultrasonography is an excellent tool to assess hepatic steatosis in the clinical setting with some limitations in patients with a low liver fat content. The detection of hepatic steatosis by ultrasonography is not influenced by liver iron.

BrachyView: initial preclinical results for a real-time in-body HDR PBT source tracking system with simultaneous TRUS image fusion.

A prototype in-body gamma camera system with integrated trans-rectal ultrasound (TRUS) and associated real-time image acquisition and analysis software was developed for intraoperative source tracking in high dose rate (HDR) brachytherapy. The accuracy and temporal resolution of the system was validated experimentally using a deformable tissue-equivalent prostate gel phantom and a full clinical HDR treatment plan. The BrachyView system was able to measure 78% of the 200 source positions with an accuracy of better than 1 mm. A minimum acquisition time of 0.28 s/frame was required to achieve this accuracy, restricting dwell times to a minimum of 0.3 s. Additionally, the performance of the BrachyView-TRUS fusion probe for mapping the spatial location of the tracked source within the prostate volume was evaluated. A global coordinate system was defined by scanning the phantom with the probe in situ using a CT scanner, and was subsequently used for co-registration of the BrachyView and TRUS fields of view (FoVs). TRUS imaging was used to segment the prostate volume and reconstruct it into a three-dimensional (3D) image. Fusion of the estimated source locations with the 3D prostate image was performed using integrated 3D visualisation software. HDR BrachyView is demonstrated to be a valuable tool for intraoperative source tracking in HDR brachytherapy, capable of resolving source dwell locations relative to the prostate anatomy when combined with TRUS.

2D monolithic silicon-diode array detectors in megavoltage photon beams: does the fabrication technology matter? A medical physicist's perspective.

A family of prototype 2D monolithic silicon-diode array detectors (MP512, Duo, Octa) has been proposed by the Centre for Medical Radiation Physics, University of Wollongong (Australia) for relative dosimetry in small megavoltage photon beams. These detectors, which differ in the topology of their 512 sensitive volumes, were originally fabricated on bulk p-type substrates. More recently, they have also been fabricated on epitaxial p-type substrates. In the literature, their performance has been individually characterized for quality assurance (QA) applications. The present study directly assessed and compared that of a MP512-bulk and that of a MP512-epitaxial in terms of radiation hardness, long-term stability, response linearity with dose, dose per pulse and angular dependence. Their measurements of output factors, off-axis ratios and percentage depth doses in square radiation fields collimated by the jaws and produced by 6 MV and 10 MV flattened photon beams were then benchmarked against those by commercially available detectors. The present investigation was aimed at establishing, from a medical physicist's perspective, how the bulk and epitaxial fabrication technologies would affect the implementation of the MP512s into a QA protocol. Based on results, the MP512-epitaxial would offer superior radiation hardness, long-term stability and achievable uniformity and reproducibility of the response across the 2D active area.

Identification of Cystic Lesions by Secondary Screening of Familial Pancreatic Cancer (FPC) Kindreds Is Not Associated with the Stratified Risk of Cancer.

OBJECTIVES: Intraductal papillary mucinous neoplasms (IPMNs) are associated with risk of pancreatic ductal adenocarcinoma (PDAC). It is unclear if an IPMN in individuals at high risk of PDAC should be considered as a positive screening result or as an incidental finding. Stratified familial pancreatic cancer (FPC) populations were used to determine if IPMN risk is linked to familial risk of PDAC. METHODS: This is a cohort study of 321 individuals from 258 kindreds suspected of being FPC and undergoing secondary screening for PDAC through the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC). Computerised tomography, endoscopic ultrasound of the pancreas and magnetic resonance imaging were used. The risk of being a carrier of a dominant mutation predisposing to pancreatic cancer was stratified into three even categories (low, medium and high) based on: Mendelian probability, the number of PDAC cases and the number of people at risk in a kindred. RESULTS: There was a median (interquartile range (IQR)) follow-up of 2 (0-5) years and a median (IQR) number of investigations per participant of 4 (2-6). One PDAC, two low-grade neuroendocrine tumours and 41 cystic lesions were identified, including 23 IPMN (22 branch-duct (BD)). The PDAC case occurred in the top 10% of risk, and the BD-IPMN cases were evenly distributed amongst risk categories: low (6/107), medium (10/107) and high (6/107) (P = 0.63). CONCLUSIONS: The risk of finding BD-IPMN was independent of genetic predisposition and so they should be managed according to guidelines for incidental finding of IPMN.

High toxicity of Bi(OH)3 and α-Bi2O3 nanoparticles towards malignant 9L and MCF-7 cells.

Here we report the extreme toxicity in vitro of Bi(OH)3 and α-Bi2O3 nanoparticles (NPs), obtained through a facile synthesis with an average single particle size of 6-10 nm, tested on malignant gliosarcoma 9L and MCF-7 human breast cancer cells. For both nanomaterials, clonogenic assays reveal a mortality of over 90% in 9L and MCF-7 cells for a concentration of 50 µg/mL after incubation for 24 h. Moreover, the NPs show a significant mortality of up to 60% in the malignant cells at the very low concentration of 6.25 µg/mL. In contrast, at the same concentration, the nanomaterials exhibit no noticeable mortality towards normal Madin-Darby canine kidney cells. The internalisation of the NPs was demonstrated using flow cytometry and confocal microscopy was used to investigate when the loss of cell viability starts. The NPs show a faster cell death in 9L cells compared with MCF-7 cells, demonstrated via the identification of apoptosis through increased sub G1 levels after 24 h of NP incubation. Cleavage is identified as the main apoptotic nuclear morphology in 9L, which suggests the presence of reactive oxygen species.

Measuring the excitations in a new S = 1/2 quantum spin chain material with competing interactions.

Recently a new one-dimensional (1D) quantum spin chain system has been reported: catena-dichloro(2-Cl-3Mpy)copper(II), (where 2-Cl-3Mpy=2-chloro-3-methylpyridine). Preliminary calculations and bulk magnetic property measurements indicate that this system does not undergo magnetic ordering down to 1.8 K and is a prime candidate for investigating frustration in a J 1/J 2 system (where the nearest neighbour interactions, J 1, are ferromagnetic and the next nearest neighbour interactions, J 2, are antiferromagnetic). Calculations predicted three possible magnetic interaction strengths for J 1 below 6 meV depending on the orientation of the ligand. For one of the predicted J 1 values, the existence of a quantum critical point is implied. A deuterated sample of catena-dichloro(2-Cl-3Mpy)copper(II) was synthesised and the excitations measured using inelastic neutron scattering. Scattering indicated the most likely scenario involves spin-chains where each chain consists of only one of the three possible magnetic excitations in this material, rather than the completely random array of exchange interactions within each chain as predicted by Herringer et al (2014 Chem. Eur. J. 20 8355-62). This indicates the possibility of tuning the chemical structure to favour a system which may exhibit a quantum critical point.

Expression of dihydropyrimidine dehydrogenase (DPD) and hENT1 predicts survival in pancreatic cancer.

BACKGROUND: Dihydropyrimidine dehydrogenase (DPD) tumour expression may provide added value to human equilibrative nucleoside transporter-1 (hENT1) tumour expression in predicting survival following pyrimidine-based adjuvant chemotherapy. METHODS: DPD and hENT1 immunohistochemistry and scoring was completed on tumour cores from 238 patients with pancreatic cancer in the ESPAC-3(v2) trial, randomised to either postoperative gemcitabine or 5-fluorouracil/folinic acid (5FU/FA). RESULTS: DPD tumour expression was associated with reduced overall survival (hazard ratio, HR = 1.73 [95% confidence interval, CI = 1.21-2.49], p = 0.003). This was significant in the 5FU/FA arm (HR = 2.07 [95% CI = 1.22-3.53], p = 0.007), but not in the gemcitabine arm (HR = 1.47 [0.91-3.37], p = 0.119). High hENT1 tumour expression was associated with increased survival in gemcitabine treated (HR = 0.56 [0.38-0.82], p = 0.003) but not in 5FU/FA treated patients (HR = 1.19 [0.80-1.78], p = 0.390). In patients with low hENT1 tumour expression, high DPD tumour expression was associated with a worse median [95% CI] survival in the 5FU/FA arm (9.7 [5.3-30.4] vs 29.2 [19.5-41.9] months, p = 0.002) but not in the gemcitabine arm (14.0 [9.1-15.7] vs. 18.0 [7.6-15.3] months, p = 1.000). The interaction of treatment arm and DPD expression was not significant (p = 0.303), but the interaction of treatment arm and hENT1 expression was (p = 0.009). CONCLUSION: DPD tumour expression was a negative prognostic biomarker. Together with tumour expression of hENT1, DPD tumour expression defined patient subgroups that might benefit from either postoperative 5FU/FA or gemcitabine.

Efficacy of gemcitabine plus erlotinib in rash-positive patients with metastatic pancreatic cancer selected according to eligibility for FOLFIRINOX: A prospective phase II study of the 'Arbeitsgemeinschaft Internistische Onkologie'.

INTRODUCTION: In metastatic pancreatic ductal adenocarcinoma (mPDAC) treatment, erlotinib is known to be more effective in patients developing skin rash. Treatment with the FOLFIRINOX regimen is only performed in fit patients following defined inclusion criteria. The present study investigates the efficacy of gemcitabine plus erlotinib (gem/erlotinib) in rash-positive patients fit for FOLFIRINOX. PATIENTS AND METHODS: For this prospective phase II study, 150 patients were recruited in 20 centres. All patients received gem/erlotinib for 4 weeks (run-in phase); the subsequent treatment was determined by the development of skin rash: patients with rash grades 1-4 continued with gem/erlotinib, rash-negative patients were switched to FOLFIRINOX. Primary study end-point was to achieve a 1-year survival rate in rash-positive patients ≥40%. RESULTS: Ninety patients were deemed positive for skin rash by the end of the run-in phase, showing a 1-year survival rate of 40.0% (95% confidence interval [CI] 29.8-50.9). Median overall survival (OS) was 10.1 months, progression-free survival (PFS) was 3.8 months and overall response rate (ORR) was 23.3%. Patients switched to FOLFIRINOX (n = 27) had a 1-year survival rate of 48.1% (95% CI 28.7-68.1), a median OS of 10.9 months, a median PFS of 6.6 months and an ORR of 33.3%. Rash-negative patients had a lower quality of life at baseline but seemed to experience an improved control of pain during FOLFIRINOX. CONCLUSIONS: First-line treatment with gem/erlotinib was effective in fit, rash-positive mPDAC patients achieving a 1-year survival rate comparable to previous reports for FOLFIRINOX. The study was registered at clinicaltrials.gov (NCT0172948) and Eudra-CT (2011-005471-17).

Intratumoural expression of deoxycytidylate deaminase or ribonuceotide reductase subunit M1 expression are not related to survival in patients with resected pancreatic cancer given adjuvant chemotherapy.

BACKGROUND: Deoxycytidylate deaminase (DCTD) and ribonucleotide reductase subunit M1 (RRM1) are potential prognostic and predictive biomarkers for pyrimidine-based chemotherapy in pancreatic adenocarcinoma. METHODS: Immunohistochemical staining of DCTD and RRM1 was performed on tissue microarrays representing tumour samples from 303 patients in European Study Group for Pancreatic Cancer (ESPAC)-randomised adjuvant trials following pancreatic resection, 272 of whom had received gemcitabine or 5-fluorouracil with folinic acid in ESPAC-3(v2), and 31 patients from the combined ESPAC-3(v1) and ESPAC-1 post-operative pure observational groups. RESULTS: Neither log-rank testing on dichotomised strata or Cox proportional hazard regression showed any relationship of DCTD or RRM1 expression levels to survival overall or by treatment group. CONCLUSIONS: Expression of either DCTD or RRM1 was not prognostic or predictive in patients with pancreatic adenocarcinoma who had had post-operative chemotherapy with either gemcitabine or 5-fluorouracil with folinic acid.