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Purpose: Develop a true real‐time implementation of MR signature matching (MRSIGMA) for free‐breathing 3D MRI with sub‐200 ms latency on the Elekta Unity 1.5T MR‐Linac. Methods: MRSIGMA was implemented on an external computer with a network connection to the MR‐Linac. Stack‐of‐stars with partial kz sampling was used to accelerate data acquisition and ReconSocket was employed for simultaneous data transmission. Movienet network computed the 4D MRI motion dictionary and correlation analysis was used for signature matching. A programmable 4D MRI phantom was utilized to evaluate MRSIGMA with respect to a ground‐truth translational motion reference. In vivo validation was performed on patients with pancreatic cancer, where 15 patients were employed to train Movienet and 7 patients to test the real‐time implementation of MRSIGMA. Dice coefficients between real‐time MRSIGMA and a retrospectively computed 4D reference were used to evaluate motion tracking performance. Results: Motion dictionary was computed in under 5 s. Signature acquisition and matching presented 173 ms latency on the phantom and 193 ms on patients. MRSIGMA presented a mean error of 1.3–1.6 mm for all phantom experiments, which was below the 2 mm acquisition resolution along the motion direction. The Dice coefficient over time between MRSIGMA and reference contours was 0.88 ± 0.02 (GTV), 0.87 ± 0.02(duodenum‐stomach), and 0.78 ± 0.02(small bowel), demonstrating high motion tracking performance for both tumor and organs at risk. Conclusion: The real‐time implementation of MRSIGMA enabled true real‐time free‐breathing 3D MRI with sub‐200 ms imaging latency on a clinical MR‐Linac system, which can be used for treatment monitoring, adaptive radiotherapy and dose accumulation mapping in tumors affected by respiratory motion. [ABSTRACT FROM AUTHOR]

Purpose: To develop a novel deep learning approach for 4D‐MRI reconstruction, named Movienet, which exploits space–time‐coil correlations and motion preservation instead of k‐space data consistency, to accelerate the acquisition of golden‐angle radial data and enable subsecond reconstruction times in dynamic MRI. Methods: Movienet uses a U‐net architecture with modified residual learning blocks that operate entirely in the image domain to remove aliasing artifacts and reconstruct an unaliased motion‐resolved 4D image. Motion preservation is enforced by sorting the input image and reference for training in a linear motion order from expiration to inspiration. The input image was collected with a lower scan time than the reference XD‐GRASP image used for training. Movienet is demonstrated for motion‐resolved 4D MRI and motion‐resistant 3D MRI of abdominal tumors on a therapeutic 1.5T MR‐Linac (1.5‐fold acquisition acceleration) and diagnostic 3T MRI scanners (2‐fold and 2.25‐fold acquisition acceleration for 4D and 3D, respectively). Image quality was evaluated quantitatively and qualitatively by expert clinical readers. Results: The reconstruction time of Movienet was 0.69 s (4 motion states) and 0.75 s (10 motion states), which is substantially lower than iterative XD‐GRASP and unrolled reconstruction networks. Movienet enables faster acquisition than XD‐GRASP with similar overall image quality and improved suppression of streaking artifacts. Conclusion: Movienet accelerates data acquisition with respect to compressed sensing and reconstructs 4D images in less than 1 s, which would enable an efficient implementation of 4D MRI in a clinical setting for fast motion‐resistant 3D anatomical imaging or motion‐resolved 4D imaging. [ABSTRACT FROM AUTHOR]

Background: Adaptive radiation treatment (ART) for locally advanced pancreatic cancer (LAPC) requires consistently accurate segmentation of the extremely mobile gastrointestinal (GI) organs at risk (OAR) including the stomach, duodenum, large and small bowel. Also, due to lack of sufficiently accurate and fast deformable image registration (DIR), accumulated dose to the GI OARs is currently only approximated, further limiting the ability to more precisely adapt treatments. Purpose: Develop a 3‐D Progressively refined joint Registration‐Segmentation (ProRSeg) deep network to deformably align and segment treatment fraction magnetic resonance images (MRI)s, then evaluate segmentation accuracy, registration consistency, and feasibility for OAR dose accumulation. Method: ProRSeg was trained using five‐fold cross‐validation with 110 T2‐weighted MRI acquired at five treatment fractions from 10 different patients, taking care that same patient scans were not placed in training and testing folds. Segmentation accuracy was measured using Dice similarity coefficient (DSC) and Hausdorff distance at 95th percentile (HD95). Registration consistency was measured using coefficient of variation (CV) in displacement of OARs. Statistical comparison to other deep learning and iterative registration methods were done using the Kruskal‐Wallis test, followed by pair‐wise comparisons with Bonferroni correction applied for multiple testing. Ablation tests and accuracy comparisons against multiple methods were done. Finally, applicability of ProRSeg to segment cone‐beam CT (CBCT) scans was evaluated on a publicly available dataset of 80 scans using five‐fold cross‐validation. Results: ProRSeg processed 3D volumes (128 × 192 × 128) in 3 s on a NVIDIA Tesla V100 GPU. It's segmentations were significantly more accurate (p<0.001$p<0.001$) than compared methods, achieving a DSC of 0.94 ±0.02 for liver, 0.88±0.04 for large bowel, 0.78±0.03 for small bowel and 0.82±0.04 for stomach‐duodenum from MRI. ProRSeg achieved a DSC of 0.72±0.01 for small bowel and 0.76±0.03 for stomach‐duodenum from public CBCT dataset. ProRSeg registrations resulted in the lowest CV in displacement (stomach‐duodenum CVx$CV_{x}$: 0.75%, CVy$CV_{y}$: 0.73%, and CVz$CV_{z}$: 0.81%; small bowel CVx$CV_{x}$: 0.80%, CVy$CV_{y}$: 0.80%, and CVz$CV_{z}$: 0.68%; large bowel CVx$CV_{x}$: 0.71%, CVy$CV_{y}$ : 0.81%, and CVz$CV_{z}$: 0.75%). ProRSeg based dose accumulation accounting for intra‐fraction (pre‐treatment to post‐treatment MRI scan) and inter‐fraction motion showed that the organ dose constraints were violated in four patients for stomach‐duodenum and for three patients for small bowel. Study limitations include lack of independent testing and ground truth phantom datasets to measure dose accumulation accuracy. Conclusions: ProRSeg produced more accurate and consistent GI OARs segmentation and DIR of MRI and CBCTs compared to multiple methods. Preliminary results indicates feasibility for OAR dose accumulation using ProRSeg. [ABSTRACT FROM AUTHOR]

Purpose: Accurate deformable registration between computed tomography (CT) and cone‐beam CT (CBCT) images of pancreatic cancer patients treated with high biologically effective radiation doses is essential to assess changes in organ‐at‐risk (OAR) locations and shapes and to compute delivered dose. This study describes the development and evaluation of a deep‐learning (DL) registration model to predict OAR segmentations on the CBCT derived from segmentations on the planning CT. Methods: The DL model is trained with CT‐CBCT image pairs of the same patient, on which OAR segmentations of the small bowel, stomach, and duodenum have been manually drawn. A transformation map is obtained, which serves to warp the CT image and segmentations. In addition to a regularity loss and an image similarity loss, an OAR segmentation similarity loss is also used during training, which penalizes the mismatch between warped CT segmentations and manually drawn CBCT segmentations. At test time, CBCT segmentations are not required as they are instead obtained from the warped CT segmentations. In an IRB‐approved retrospective study, a dataset consisting of 40 patients, each with one planning CT and two CBCT scans, was used in a fivefold cross‐validation to train and evaluate the model, using physician‐drawn segmentations as reference. Images were preprocessed to remove gas pockets. Network performance was compared to two intensity‐based deformable registration algorithms (large deformation diffeomorphic metric mapping [LDDMM] and multimodality free‐form [MMFF]) as baseline. Evaluated metrics were Dice similarity coefficient (DSC), change in OAR volume within a volume of interest (enclosing the low‐dose PTV plus 1 cm margin) from planning CT to CBCT, and maximum dose to 5 cm3 of the OAR [D(5cc)]. Results: Processing time for one CT‐CBCT registration with the DL model at test time was less than 5 seconds on a GPU‐based system, compared to an average of 30 minutes for LDDMM optimization. For both small bowel and stomach/duodenum, the DL model yielded larger median DSC and smaller interquartile variation than either MMFF (paired t‐test P < 10−4 for both type of OARs) or LDDMM (P < 10−3 and P = 0.03 respectively). Root‐mean‐square deviation (RMSD) of DL‐predicted change in small bowel volume relative to reference was 22% less than for MMFF (P = 0.007). RMSD of DL‐predicted stomach/duodenum volume change was 28% less than for LDDMM (P = 0.0001). RMSD of DL‐predicted D(5cc) in small bowel was 39% less than for MMFF (P = 0.001); in stomach/duodenum, RMSD of DL‐predicted D(5cc) was 18% less than for LDDMM (P < 10−3). Conclusions: The proposed deep network CT‐to‐CBCT deformable registration model shows improved segmentation accuracy compared to intensity‐based algorithms and achieves an order‐of‐magnitude reduction in processing time. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the dosimetric impact of magnetic (B) field on varying air cavities in rectum patients treated on the hybrid 1.5 T MR‐linac. Methods: Artificial air cavities of varying diameters (0.0, 1.0, 1.5, 2.0, 2.5, 3.0, and 5.0 cm) were created for four rectum patients (two prone and two supine). A total of 56 plans using a 7 MV flattening filter‐free beam were generated with and without B‐field. Reference intensity‐modulated radiation therapy treatment plans without air cavity in the presence and absence of B‐field were generated to a total dose of 45/50 Gy. The reference plans were copied and recalculated for the varying air cavities. D95(PTV45–PTV50), D95(PTV50–aircavity), V50(PTV50–aircavity), Dmax(PTV50–aircavity), and V110%(PTV50–aircavity) were extracted for each patient. Annulus rings of 1‐mm‐diameter step size were generated for one of the air cavity plans (3.0 cm) for all four patients to determine Dmax (%) and V110% (cc) within each annulus. Results: In the presence of B‐field, hot spots at the cavity interface start to become visible at ~1 cm air cavity in both supine and prone positioning due to electron return effect (ERE). In the presence of B‐field Dmax and V110% varied from 5523 ± 49 cGy and 0.09 ± 0.16 cc for 0 cm air cavity size to 6050 ± 109 cGy and 11.6 ± 6.7 cc for 5 cm air cavity size. The hot spots were located within 3 mm inside the rectal‐air interface, where Dmax increased from 110.4 ± 0.5% without B‐field to 119.2 ± 0.8 % with B‐field. Conclusions: Air cavities inside rectum affects rectum plan dosimetry due ERE. Location and magnitude of hot spots are dependent on the size of the air cavity. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to characterize the efficacy and safety of stereotactic body radiation therapy (SBRT) versus conventionally fractionated radiation therapy with concurrent chemotherapy (CFRT) for the definitive treatment of locally advanced pancreatic cancer. The primary outcome measure was efficacy, defined by 2-year overall survival (OS). Secondary outcomes were incidence of any grade 3/4 toxicity and 1-year OS.Methods: A PICOS/PRISMA/MOOSE selection protocol was used to identify eligible studies. Inclusion criteria were: 1) patients diagnosed with locally advanced N0-1 M0 pancreatic cancer; 2) CFRT 1.8 to 2.0 Gy/fraction with chemotherapy per protocol or SBRT ≥5 Gy/fraction in ≤5 fractions; 3) either no control group or another definitive chemotherapy or radiation therapy arm; 4) at least 1 of the outcome measures reported; and 5) single or multi-arm phase 2/3 prospective study for CFRT and/or phase 1/2 or retrospective study for SBRT. Neoadjuvant and/or adjuvant chemotherapy was prescribed per protocol specifications. Weighted random effects meta-analyses were conducted using the DerSimonian and Laird method to characterize summary effect sizes for each outcome.Results: A total of 470 studies were initially screened; of these, 9 studies assessed SBRT and 11 studies assessed CFRT. For SBRT, the median dose was 30 Gy, and the most common regimen was 30 Gy/5 fractions. For CFRT, doses ranged from 45 to 54 Gy in 1.8- to 2.0-Gy fractions, with the majority of studies delivering 50.4 Gy in 28 fractions with concurrent gemcitabine. The random effects estimate for 2-year OS was 26.9% (95% CI, 20.6%-33.6%) for SBRT versus 13.7% (95% CI, 8.9%-19.3%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for 1-year OS was 53.7% (95% CI, 39.3%-67.9%) for SBRT versus 49.3% (95% CI, 39.3%-59.4%) for CFRT, and was not statistically significant. The random effects estimate for acute grade 3/4 toxicity was 5.6% (95% CI, 0.0%-20.0%) for SBRT versus 37.7% (95% CI, 24.0%-52.5%) for CFRT and was statistically significant in favor of SBRT. The random effects estimate for late grade 3/4 toxicity was 9.0% for SBRT (95% CI, 3.3%-17.1%) versus 10.1% (95% CI, 1.8%-23.8%) for CFRT, which was not statistically significant.Conclusion: These results suggest that SBRT for LAPC may result in a modest improvement in 2-year OS with decreased rates of acute grade 3/4 toxicity and no change in 1-year-OS or late toxicity. Further study into the use of stereotactic body radiation therapy for these patients is needed. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC). Methods: A consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8‐4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan–Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed. Results: After radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053). Conclusions: EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed. We have investigated the role of escalated radiation dose in treatment of unresectable extrahepatic cholangiocarcinoma. Escalated dose radiation therapy did not significantly improve overall survival or local control. [ABSTRACT FROM AUTHOR]

Abstract: A new bis‐triazacyclononane tris‐pyridyl N9‐azacryptand ligand is prepared via a convenient one‐pot [2+3] condensation reaction between triazacyclononane and 2,6‐bis(bromomethyl) pyridine in the presence of M2CO3 (M=Li, Na, K). The proton, lithium, sodium, potassium and lead(II) complexes of the ligand are characterised in the solid state. Preliminary solution‐phase competition experiments indicate that the cryptand ligand preferentially binds lead(II) in the presence of sodium, calcium, potassium and zinc cations in methanol solution. [ABSTRACT FROM AUTHOR]

Background: The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation.Methods: Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value.Results: Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P < .0001 for both arms combined). This association remained true on a multivariate analysis that allowed for lymph node status (hazard ratio, 0.41; 95% confidence interval, 0.27-0.63; P < .0001).Conclusions: In the current sample, MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Treatment methods for intrahepatic cholangiocarcinoma (ICC) have improved, but their impact on outcome remains unclear. We evaluated the outcomes of patients definitively treated with resection, radiation, and chemotherapy for ICC, stratified by era.Methods: Clinico-pathologic characteristics, cause of death, disease-specific survival (DSS), and intrahepatic progression-free survival (IPFS) were compared among patients who underwent resection, radiation, or chemotherapy as definitive treatment strategies for ICC (without distant organ metastasis) between 1997 and 2015. Variables were also analyzed by era (1997-2006 [early] or 2007-2015 [late]) within each group.Results: Among 362 patients in our cohort, 122 underwent resection (early, 38; late, 84), 85 underwent radiation (early, 17; late, 68), and 148 underwent systemic chemotherapy alone (early, 51; late, 97) as definitive treatment strategies, and 7 patients received best supportive care. In the resection group, the 3-year DSS rate was 58% for the early era and 67% for the late era (P = .036), and the 1-year IPFS was 50% for the early era and 75% for the late era (P = .048). In the radiation group, the 3-year DSS was 12% for the early era and 37% for the late era (P = .048), and the 1-year IPFS was 48% for the early era and 64% for the late era (P = .030). In the chemotherapy group, DSS and IPFS did not differ by era. Patients treated with chemotherapy developed liver failure at the time of death significantly more frequently than patients treated with resection (P < .001) or radiation (P < .001). Multivariable analysis identified local therapy (resection or radiation) as a sole predictor of death without liver failure.Conclusion: Survival outcomes have improved for local therapy-based definitive treatment strategies for ICC, which may be attributable to maintaining control of intrahepatic disease, thereby reducing the occurrence of death due to liver failure. Cancer 2017;123:1354-1362. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Previous studies have suggested that preoperative chemoradiation (CRT) is associated with an improved margin-negative resection rate among patients who undergo pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, the optimal preoperative regimen has not been established.Methods: All patients with PDAC who received chemotherapy and/or CRT followed by PD between 1999 and 2014 were retrospectively reviewed. The effects of 2 external-beam radiation regimens-a standard course of 50.4 Gy in 28 fractions and a hypofractionated course of 30 Gy in 10 fractions-were compared. Differences in clinicopathologic characteristics, locoregional recurrence (LR), and overall survival (OS) were assessed.Results: Among 472 patients who received preoperative therapy, 224 (47.5%) received 30 Gy, 221 (46.8%) received 50.4 Gy, and 27 (5.7%) received chemotherapy alone. Patients who received 50.4 Gy were more likely to have advanced-stage disease and to have received induction and postoperative chemotherapy, but there was no difference in the R1 margin status, treatment effect, LR, or OS between the 2 radiation groups (all P values > .05). Patients who received preoperative CRT had a lower rate of LR than patients who received preoperative chemotherapy alone (P < .01). In a multivariate Cox proportional hazards analysis, 50.4 Gy was associated with OS and LR similar to those associated with 30 Gy, whereas the absence of preoperative radiation was associated with a higher rate of LR (odds ratio, 2.21; 95% confidence interval, 1.04-4.70) and similar OS.Conclusions: Preoperative hypofractionated CRT was associated with similar local control and OS in comparison with standard CRT in patients undergoing PD for PDAC. The use of chemotherapy alone without CRT was associated with poorer local control but similar survival. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2671-2679. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

The emergence and success of stereotactic body radiation therapy (SBRT) for the treatment of lung cancer have led to its rapid adoption for liver cancers. SBRT can achieve excellent results for small liver tumors. However, the vast majority of physicians interpret SBRT as meaning doses of radiation (range, 4-20 Gray [Gy]) that may not be ablative but are delivered within about 1 week (ie, in 3-6 fractions). Adherence to this approach has limited the effectiveness of SBRT for large liver tumors (>7 cm) because of the need to reduce doses to meet organ constraints. The prognosis for patients who present with large liver tumors is poor, with a median survival ≤12 months, and most of these patients die from tumor-related liver failure. Herein, the authors present a comprehensive solution to achieve ablative SBRT doses for patients with large liver tumors by using a combination of classic, modern, and novel concepts of radiotherapy: fractionation, dose painting, motion management, image guidance, and simultaneous integrated protection. The authors discuss these concepts in the context of large, inoperable liver tumors and review how this approach can substantially prolong survival for patients, most of whom otherwise have a very poor prognosis and few effective treatment options. Cancer 2016;122:1974-86. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Recent literature suggests that the benefit of adjuvant chemotherapy (aCT) for rectal cancer patients might depend on the response to neoadjuvant chemoradiation (CRT). Aim was to evaluate whether the effect of aCT in rectal cancer is modified by response to CRT and to identify which patients benefit from aCT after CRT, by means of a pooled analysis of individual patient data from 13 datasets. Patients were categorized into three groups: pCR (ypT0N0), ypT1-2 tumour and ypT3-4 tumour. Hazard ratios (HR) for the effect of aCT were derived from multivariable Cox regression analyses. Primary outcome measure was recurrence-free survival (RFS). One thousand seven hundred and twenty three (1723) (52%) of 3,313 included patients received aCT. Eight hundred and ninety eight (898) patients had a pCR, 966 had a ypT1-2 tumour and 1,302 had a ypT3-4 tumour. For 122 patients response, category was missing and 25 patients had ypT0N+. Median follow-up for all patients was 51 (0-219) months. HR for RFS with 95% CI for patients treated with aCT were 1.25(0.68-2.29), 0.58(0.37-0.89) and 0.83(0.66-1.10) for patients with pCR, ypT1-2 and ypT3-4 tumours, respectively. The effect of aCT in rectal cancer patients treated with CRT differs between subgroups. Patients with a pCR after CRT may not benefit from aCT, whereas patients with residual tumour had superior outcomes when aCT was administered. The test for interaction did not reach statistical significance, but the results support further investigation of a more individualized approach to administer aCT after CRT and surgery based on pathologic staging. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to develop a novel algorithm to create a robust internal respiratory signal (IRS) for retrospective sorting of four-dimensional (4D) computed tomography (CT) images. Methods: The proposed algorithm combines information from the Fourier transform of the CT images and from internal anatomical features to form the IRS. The algorithm first extracts potential respiratory signals from low-frequency components in the Fourier space and selected anatomical features in the image space. A clustering algorithm then constructs groups of potential respiratory signals with similar temporal oscillation patterns. The clustered group with the largest number of similar signals is chosen to form the final IRS. To evaluate the performance of the proposed algorithm, the IRS was computed and compared with the external respiratory signal from the real-time position management (RPM) system on 80 patients. Results: In 72 (90%) of the 4D CT data sets tested, the IRS computed by the authors’ proposed algorithm matched with the RPM signal based on their normalized cross correlation. For these data sets with matching respiratory signals, the average difference between the end inspiration times (Δtins) in the IRS and RPM signal was 0.11 s, and only 2.1% of Δtins were more than 0.5 s apart. In the eight (10%) 4D CT data sets in which the IRS and the RPM signal did not match, the average Δtins was 0.73 s in the nonmatching couch positions, and 35.4% of them had a Δtins greater than 0.5 s. At couch positions in which IRS did not match the RPM signal, a correlation-based metric indicated poorer matching of neighboring couch positions in the RPM-sorted images. This implied that, when IRS did not match the RPM signal, the images sorted using the IRS showed fewer artifacts than the clinical images sorted using the RPM signal. Conclusions: The authors' proposed algorithm can generate robust IRSs that can be used for retrospective sorting of 4D CT data. The algorithm is completely automatic and requires very little processing time. The algorithm is cost efficient and can be easily adopted for everyday clinical use. [ABSTRACT FROM AUTHOR]

BACKGROUND The current study was conducted to determine whether quantified pathologic response assessed as a percentage of residual tumor cells is predictive of recurrence-free survival (RFS) in patients with rectal cancer. METHODS The authors studied 251 patients with rectal adenocarcinoma who were treated with neoadjuvant chemoradiation and radical resection. Quantified pathologic response was defined as an estimated percentage of residual cancer cells in relation to the tumor bed: complete, no residual cancer cells; near-complete, ≤ 5% residual cancer cells; major, > 5%, and < 50% residual cancer cells; and minor, ≥ 50% residual cancer cells. The reproducibility of quantified pathologic response between 2 pathologists was assessed using tumors from 55 randomly selected patients who did not demonstrate a complete response. RESULTS Pathologic response was complete in 21% of patients, near-complete in 20% of patients, major in 37% of patients, and minor in 22% of patients. Nineteen percent of patients had ypT0N0 disease, 27% had ypT1-2N0 disease, 21% had ypT3-4N0 disease, and 33% had N+ disease. The 5-year RFS rates by category of quantified pathologic response were as follows: complete, 95%; near-complete, 88%; major, 69%; and minor, 61% ( P < .001). Major and minor response, high histologic grade, and perineural invasion were found to be significant predictors of decreased RFS on multivariate analysis. The 5-year RFS rates for patients with ypT3-4 or N+ disease were better for those with a near-complete response (94%) compared with those with a major (64%) or minor (61%) response ( P < .02). Moderate to substantial agreement was observed between the 2 pathologists (κ = 0.72). CONCLUSIONS Quantified pathologic response is a predictor of RFS in patients with rectal adenocarcinoma and stratifies patients with high pathologic stage disease. Cancer 2013;119:4231-4241. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND Weekly or daily cisplatin and 5-fluorouracil (5-FU)-based chemoradiation was evaluated for patients with locally advanced squamous cell carcinoma (SCC) of the anal canal treated at a single institution over a 20-year period. METHODS A retrospective, single-institution analysis was conducted of patients receiving concurrent 5-FU/cisplatin and radiotherapy for locally advanced SCC from 1989 to 2009. Endpoints included clinical complete response rate, local recurrence rate, colostomy-free survival, disease-free survival (DFS), overall survival, and treatment-related toxicity. RESULTS A total of 197 patients were evaluable. The majority had American Joint Committee on Cancer stage II (41%) or stage III (46%) disease; most were T2 (44%) or T3 (27%); bulky nodal disease (N2-N3) was noted in 24% of patients. Patients received weekly (20 mg/m2) or daily (4 mg/m2) cisplatin during radiotherapy. Median radiation dose was 55 Gy. Clinical complete response was observed in 185 patients (94%). After a median follow-up of 8.6 years, local recurrence rate was 11%. Sixteen patients (8%) developed distant metastases. The 5-year DFS was 81%, the 5-year overall survival was 86%, and the 5-year colostomy-free survival was 88%. By univariate analysis, N-stage was a poor prognostic indicator for 5-year DFS ( P = .02, 95% confidence interval = 1.17-2.01) and distant metastases ( P = .046, 95% confidence interval = 1.09-2.13). Increased T-stage correlated with the necessity for salvage surgery ( P = .01). CONCLUSIONS The combination of weekly/daily cisplatin and 5-FU-based chemotherapy with concurrent radiotherapy is an effective regimen, and our long-term results indicate that cisplatin is an alternative to mitomycin C and may be considered for the treatment of locally advanced SCC of the anal canal. Cancer 2013;119:3769-3775. © 2013 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Experience with preoperative therapy for other cancers has led to an assumption that borderline resectable pancreatic cancers can be converted to resectable cancers with preoperative therapy. In this study, the authors sought to determine the rate at which neoadjuvant therapy is associated with a reduction in the size or stage of borderline resectable tumors. METHODS: Patients who had borderline resectable pancreatic cancer and received neoadjuvant therapy before potentially undergoing surgery at the authors' institution between 2005 and 2010 were identified. The patients' pretreatment and post-treatment pancreatic protocol computed tomography images were rereviewed to determine changes in tumor size or stage using modified Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1) and standardized anatomic criteria. RESULTS: The authors identified 129 patients who met inclusion criteria. Of the 122 patients who had their disease restaged after receiving preoperative therapy, 84 patients (69%) had stable disease, 15 patients (12%) had a partial response to therapy, and 23 patients (19%) had progressive disease. Although only 1 patient (0.8%) had their disease downstaged to resectable status after receiving neoadjuvant therapy, 85 patients (66%) underwent pancreatectomy. The median overall survival duration for all 129 patients was 22 months (95% confidence interval, 14-30 months). The median overall survival duration for the patients who underwent pancreatectomy was 33 months (95% confidence interval, 25-41 months) and was not associated with RECIST response ( P = .78). CONCLUSIONS: Radiographic downstaging was rare after neoadjuvant therapy, and RECIST response was not an effective treatment endpoint for patients with borderline resectable pancreatic cancer. The authors concluded that these patients should undergo pancreatectomy after initial therapy in the absence of metastases. Cancer 2012. © 2012 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several grading schemes for the extent of residual tumor in posttreatment pancreaticoduodenectomy (PD) specimens have been proposed. However, the prognostic significance of these grading schemes is unknown. METHODS: Histopathologic slides of 223 cases who received neoadjuvant chemoradiation and PD were reviewed. The extent of residual tumor was graded using both the College of American Pathologists (CAP) and the Evans grading systems. The grading results were correlated with clinicopathological parameters and survival. RESULTS: Among the 223 patients, 6 patients (2.7%) showed pathologic complete response (pCR; CAP grade 0 or Evans grade IV), 36 cases (16.1%) had minimal residual tumor (CAP grade 1 or Evans grade III), 124 cases (55.6%) had moderate response (CAP grade 2 or Evans grade IIb), and 57 cases (25.6%) had poor response (CAP grade 3, where 18 had Evans grade I and 39 had Evans grade IIa response). Patients with pCR or minimal residual tumor (response group 1) had better survival rates than those with moderate and poor response (response group 2). Response group 1 patients had lower posttherapy tumor and American Joint Committee on Cancer stages and lower rates of lymph node metastasis, positive resection margin, and recurrence and/or metastasis. Grading the extent of residual tumor is an independent prognostic factor for overall survival in multivariate analysis. CONCLUSIONS: pCR or minimal residual tumor in posttreatment PD specimens correlate with better survival in patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapy and PD. Histologic grading of the extent of residual tumor in PD specimen is an important prognostic factor in patients with pancreatic ductal adenocarcinoma who received neoadjuvant therapies. Cancer 2012;118: 3182-90. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

BACKGROUND: Preoperative chemoradiation for rectal cancer can decrease the number of evaluable lymph nodes. Hence, the prognostic role of lymph node evaluation in patients with rectal cancer who receive preoperative chemoradiation is unclear. The authors of this report evaluated the prognostic impact of the number of lymph nodes examined in patients with rectal cancer who had negative lymph nodes based on the pathologic extent of disease (ypN0) after they received preoperative chemoradiation. METHODS: Between 1990 and 2004, 372 patients with nonmetastatic rectal adenocarcinoma received preoperative chemoradiation followed by mesorectal excision and had ypN0 disease. The median radiation dose was 45 gray, and 68% of patients received adjuvant chemotherapy. RESULTS: Patients had a median of 7 lymph nodes examined after preoperative chemoradiation. Compared with patients who had ≤7 lymph nodes examined, patients who had >7 lymph nodes had higher 5-year rates of freedom from relapse (86% vs 72%; log-rank P = .005) and cancer-specific survival (95% vs 86%; log-rank P = .0004), but no significant difference was observed in the overall survival rate (87% vs 81%; log-rank P = .07). Multivariate Cox proportional models demonstrated that patients who had >7 lymph nodes examined had a significantly lower risk of relapse (hazard ratio [HR], 0.39; P = .003) and death from rectal cancer (HR, 0.45; P = .04) but a similar risk of all-cause mortality (HR, 0.75; 95% CI, 0.46-1.20; P = .23) compared with patients who had ≤7 lymph nodes examined. CONCLUSIONS: The number of lymph nodes examined was associated independently with disease relapse and cancer-specific survival in patients with rectal cancer who had ypN0 disease after receiving preoperative chemoradiation. Hence, the authors concluded that the number of negative lymph nodes examined may be a prognostic factor in patients with rectal cancer who receive preoperative chemoradiation. Cancer 2011;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

The article presents a study which assesses the long-term quality of life (QoL) of anal cancer patients after radiotherapy. The study used Functional Assessment of cancer Therapy-Colorectal (FACT-C) to evaluate Qol; thus, questionnaires was mailed to 80 patients who undergone radiotherapy. The study found that patients treated with radiotherapy for anal cancer has acceptable overall long-term Qol scores but with poor sexual function scores.

The article presents the authors' views about the use of stereotactic body radiotherapy (SBRT) for the patients suffering from pancreatic cancer. The authors say that SBRT is capable of precisely delivering high doses of radiation to small tumor volumes. They further say that the most meaningful outcome metric of pancreatic cancer treatment is median survival.

INTRAOPERATIVE RADIATION THERAPY (IORT) is a treatment option that directly irradiates a surgically exposed tumor or tumor bed while preventing radiation exposure of normal tissues. THIS ARTICLE DISCUSSES the high-dose-rate intraoperative radiation therapy (HDR-IORT) technique by reviewing the roles of IORT team members, discussing needed equipment and supplies, describing quality assurance processes, explaining the HDR-IORT treatment delivery procedure, and reviewing the post-treatment phase. [ABSTRACT FROM AUTHOR]

The article presents a study which hypothesized that presurgical (postCTRT) stage would also correlate better with patient outcome than the baseline stage for localized gastric cancer. Patients in the study were staged with baseline endoscopic ultrasonography (EUS) and laparoscopy and they received induction chemotherapy, then CTRT (45 Gy), and had an attempted surgery. The study found that thirty-five had all 3 sets of staging, baseline, presurgical, and postsurgical.

The article discusses a study on the difference in outcomes for patients with unresectable locally advanced pancreatic cancer (LAPC) who were treated with either chemoradiation therapy (CR) or induction chemotherapy followed by CR (CCR). Under the study, 247 patients were given CR while 76 had CCR. No significant difference in the patterns of treatment failure in using induction chemotherapy was found. Induction chemotherapy may be used to determine patients with LAPC for optimal benefit from consolidative CR.

The article presents a study which examined the predictive factors for pathologic complete response and tumor downstaging after preoperative chemoradiation for rectal cancer. The study employed 562 patients with nonmetastatic rectal adenocarcinoma who received preoperative chemoradiation and underwent mesorectal excision between 1989 and 2004. The study found that 19% of patients achieved a pathologic complete response, whereas 20% had only microscopic residual disease at surgery, and 61% had macroscopic residual disease at surgery.

The article focuses on the use of neoadjuvant radiochemotherapy in esophageal carcinoma. It is said that local response to neoadjuvant chemoradiotherapy correlates with improvements in survival and is predictive of survival in malignancies. It is also stated that the risk of neoadjuvant therapy is delaying surgery in patients who do not respond to chemotherapy.

A review of the article "Another Solution That Enables Ablative Radiotherapy for Large Liver Tumors: Percutaneous Interstitial High-Dose Rate Brachytherapy" by authors Shyamal Patel, Omar Ragab and Mitchell Kamrava, which was published on May 31, 2016 in the Wiley Online Library, is presented.