Adaptive radiation therapy: When,how and what are the benefits that literature provides?

PurposeTo identify from the current literature when is the right time to replan and to assign thresholds for the optimum process of replanning. Nowadays, adaptive radiotherapy (ART) for head and neck cancer plays an exceptional role consisting of an evaluation procedure of the prominent anatomical and dosimetric variations. By performing complex radiotherapy methods, the credibility of the therapeutic result is crucial. Image guided radiotherapy (IGRT) was developed to ensure locoregional control and thus changes that might occur during radiotherapy be dealt with.Materials and methodsAn electronic research of articles published in PubMed/MEDLINE and Science Direct databases from January 2004 to October 2020 was performed. Among a total of 127 studies assessed for eligibility, 85 articles were ultimately retained for the review.ResultsThe most noticeable changes have been reported in the middle fraction of the treatment. Therefore, the suggested optimal time to replan is between the third and the fourth week. Anatomical deviations > 1 cm in the external contour, average weight loss > 10%, violation in the dose coverage of the targets > 5%, and violation in the dose of the peripherals were some of the thresholds that are currently used, and which lead to replanning.ConclusionART may decrease toxicity and improve local-control. Whether it is beneficial or not, depends ultimately on each patient. However, more investigation of the changes should be performed in future prospective studies to obtain more accurate results.     

Toxicity and time lapse between immunotherapy and stereotactic radiotherapy of brain metastases

PurposeStereotactic radiotherapy (SRT) is the standard treatment for brain metastases of non-small-cell lung cancer (NSCLC) and melanoma, mostly in combination with immunotherapy. The objective was to retrospectively evaluate the influence of the time-lapse between immunotherapy and stereotactic radiotherapy on toxicity.Patients and methodsFrom 2016 to 2019, 59 patients treated with SRT for 103 brain metastases of NSCLC (60%) and melanoma (40%) in combination with concomitant immunotherapy (≤ 30 days) were included. The prescribed dose was 20 Gy/1f or 33 Gy/3f at the isocentre and 14 Gy or 23.1 Gy (70%) respectively at the PTV envelope (PTV = GTV + 2 mm). The mean tumour diameter was 14 mm (4–52 mm). The immunotherapies used were anti-PD1 and anti-PDL1. The 103 metastases were classified into 3 groups according to the time-lapse between instatement of immunotherapy and instatement of SRT for the patient concerned: 7 (7%) in group A (≤ 7 days), 38 (37%) in group B (7 to 14 days) and 58 (56%) in group C (14 to 30 days).ResultsThe mean follow-up was 10.1 months. The median overall survival was 11.5 months for NSCLC and 12.5 months for melanoma. The percentage of local control (LC) at one year was 65.1% (93.6% for NSCLC and 26.5% for melanoma). The time-lapse between immunotherapy and SRT was not a significant predictor of LC (P = 0.86), while the histology was (P < 0.001). The proportion of grade ≥ 3 toxicities was 5.1%, and that of radionecrosis was 9.7% (among these patients, 80% were non-symptomatic): 0%, 13.1% and 8.6% for groups A, B and C respectively. The time-lapse between immunotherapy and SRT was not a significant predictor of toxicity. Only tumour volume was a significant predictive factor (P = 0.03).ConclusionThe time lapse between immunotherapy and SRT does not influence brain toxicity. The tumour volume remains the main factor.     

Impact of adjuvant radiotherapy on biological and clinical parameters in right-sided breast cancer

PurposeIn patients with right-sided breast cancer (BC) the liver might be partially irradiated during adjuvant radiotherapy (RT). Thus, we performed a prospective observational study to evaluate the dose delivered to the liver, and its potential biological impact.Patients and methodsWe enrolled 34 patients with right-sided BC treated with adjuvant RT. The RT schedules were either the Canadian (42.5 Gy in 16 fx) or standard fractionated (50 Gy in 25 fx) regimen respectively with 9 (26.5%) and 25 (73.5%) patients each, ± a boost of 10–16 Gy. Each patient had a complete blood count and liver enzymes analysis, before starting and during the last week of treatment.ResultsA significant decrease in white blood cells and thrombocytes counts was observed during RT. We observed a significant correlation between certain hepatic parameters and the volume of the irradiated liver and/or the mean liver dose. A significant correlation between the volume of the right lung and the liver mean dose was found (P = 0.008). In the bivariate analysis, a significant correlation between fatigue and the white blood cell count's evolution was observed (P < 0.025).ConclusionWith the standard RT technique, incidental irradiation of the liver was documented in a large number of patients, and some significant hepatic parameters alterations were observed, without an apparent clinical impact, but this study cannot exclude them. The liver mean dose was correlated with the right lung volume suggesting that deep inspiration breath hold (DIBH) techniques may represent a way to decrease the liver dose. These findings need to be evaluated in further larger studies.     

I125 irradiation stent for treatment of hepatocellular carcinoma with portal vein thrombosis: A meta-analysis

PurposeA meta-analysis aimed to systematically evaluate the safety and efficiency of I¹²⁵ irradiation stent placement for patients with hepatocellular carcinoma (HCC) combined with portal vein tumor thrombosis (PVTT).Materials and methodsThe Cochrane library, PubMed/Medline, EMBASE, CNKI, Wanfang Data and CQVIP were systematically screened out from the earliest to December 2019. The qualities of all included studies were assessed. The primary endpoints were the 6-month, 12-month stent cumulative patency rate and 6-month, 12-month, 24-month overall survival rate while the secondary endpoints were the objective response rate of PVTT, main portal venous pressure changes and treatment-related adverse events. Our meta-analysis was conducted using Stata 12.0 software.ResultsTotally seven studies with 1018 patients were included in the final analysis, in which 602 patients received TACE and I¹²⁵ irradiation stent placement, and 416 patients in control group underwent TACE and stent placement without endovascular brachytherapy (EVBT). Meta-analysis showed that the I¹²⁵ irradiation stent improved the cumulative stent patency rates in 6 months [OR = 1.65, 95% CI (1.32–2.05), P < 0.001] and 12 months [OR = 2.55, 95% CI (1.90–3.42), P < 0.001] and the survival rates in 6 months [OR = 1.77, 95% CI (1.41–2.22), P < 0.001], 12 months [OR = 3.14, 95% CI (2.24–4.40), P < 0.001] and 24 months [OR = 7.39, 95% CI (3.55–15.41), P < 0.001]. However, there was no difference in the objective response rate of PVTT [OR = 1.13, 95% CI (0.87–1.48), P = 0.365], main portal venous pressure and the occurrence adverse event [OR = 0.88, CI = 0.72–1.08, P = 0.212] between two groups.ConclusionI¹²⁵ irradiation stent seems to be more effective in treating hepatocellular carcinoma with portal vein tumor thrombosis. The usage of portal vein stent combined endovascular brachytherapy has the potential to act as an alternative therapy for HCC with PVTT. On account of the limitation of studies included, more studies with high-level evidence, such as RCTs, are requisite to support the above promising results.     

Image-guided total-body irradiation with a movable electronic portal imaging device for bone marrow transplant conditioning

IntroductionTo prevent radiation pneumonitis following total body irradiation (TBI) clinicians usually use lung shield blocks. The correct position of these shields relative to the patient's lungs is usually verified via mega-voltage imaging and computed radiographic (CR) films. In order to improve this time-consuming procedure, we developed in our department a dedicated, movable, real-time imaging system for image-guided TBI.Material & MethodsThe system consists of an electronic portal imaging device (EPID) mounted on a dedicated support whose motion along a rail can be controlled from the linac console outside the bunker room. Images are acquired online using a stand-alone console. To test the system efficacy we retrospectively analyzed data of lung blocks positioning from two groups of 10 patients imaged with EPID or CR-films, respectively.ResultsThe median number of portal images per fraction was 2 (range 1-5) and 1 (range 1-2) for the EPID and the CR-film system, respectively. The minimum time required for an EPID image acquisition, without interpretation and no need of patient position correction in the bunker, was 20 seconds against 214 seconds for the CR-film. Lung shielding positioning in the right-left and superior-inferior directions was improved using the EPID system (p< 0.01).ConclusionsCompared to CR-films, our movable real-time imaging EPID system is a simple technical solution able to reduce the minimum imaging time for lung shielding by a factor of 10. With the increased possibility to acquire more images as compared to CR-film system the EPID system has the potential to improve patient alignment, as well as patient's comfort and overall setup time.     

Effect of scan projection radiography coverage on tube current modulation in pediatric and adult chest CT

PurposeTo investigate the effect of scan projection radiography (SPR) coverage on tube current modulation in pediatric and adult thoracic CT examinations.MethodsSixty pediatric and 60 adult chest CT examinations were retrospectively studied to determine the incidence rate of examinations involving SPRs that did not include the entire image volume (IV) or the entire primarily exposed body volume (PEBV). The routine chest CT acquisition procedure on a modern 64-slice CT system was imitated on five anthropomorphic phantoms of different size. SPRs of varying length were successively acquired. The same IV was prescribed each time and the computed tube current modulation plan was recorded. The SPR boundaries were altered symmetrically by several steps of ±10 mm with respect to the IV boundaries.ResultsThe upper IV boundary was found to be excluded from SPR in 52% of pediatric and 40% adult chest CT examinations. The corresponding values for the lower boundary were 15% and 20%, respectively. The computed tube current modulation was found to be considerably affected when the SPR did not encompass the entire IV. SPR deficit of 3 cm was found to induce up to 46% increase in the computed tube current value to be applied during the first tube rotations over lung apex.ConclusionsThe tube current modulation mechanism functions properly only if the IV set by the operator is entirely included in the localizing SPR image. Operators should cautiously set the SPR boundaries to avoid partial exclusion of prescribed IV from SPRs and thus achieve optimum tube current modulation.     

No touch isolation technique for the prevention of postoperative recurrence of hepatocellular carcinoma after liver transplantation-combined with trans-arterial radioembolization

IntroductionTransarterial radioembolization (TARE) is recently emerging treatment modality using radiation from Yttrium-90 through the transarterial approach. It usually is used in the intermediate stage and unresectable hepatocellular carcinoma (HCC).No touch isolation technique is a way to prevent the spread of tumors by pre-ligating the vessels around the tumor with minimal touch during surgery. We hoped that if we were to use these techniques, we would be able to control all viable tumors before liver transplantation. Then we could get better outcomes even in the advanced hepatocellular carcinoma patients.MethodsWe performed living donor liver transplantation using no touch isolation technique in the patients who had multinodular hepatocellular carcinoma and extremely high AFP, PIVKA-II level after TARE and conventional TACE.Results36 years old female patient had liver cirrhosis with hepatitis B virus infection and multiple hepatocellular carcinoma in both lobes. Hepatologist decided to do TARE and additional conventional TACE for viable tumors. After that treatment, AFP and PIVKA-II level were dramatically decreased, we decided to proceed of living donor liver transplantation because the patient's treatment response was extremely good.ConclusionsNo touch isolation technique combined with TARE for recipient hepatectomy might be helpful in advanced stage hepatocellular carcinoma patients.     

Optic nerve motion and gaze direction: Their impact on intraorbital tumor radiotherapy

PurposeManagement of inter- and intra-fraction movements of target volumes and organs at risk (OARs) during radiotherapy is essential. While there is little OAR or target volume movement, the movements and orientation of the eyes can be significant during radiotherapy and they can affect the position of the optic nerve. The objective of the present study was to assess the variations of the optic nerve position due to gaze direction and to discuss their clinical consequences on the radiation treatment of intraorbital tumors.Material and methodsThree patients without a history of oculomotor nerve palsy underwent six CT acquisitions with a thermoplastic mask: eyes open with different gaze directions (straight ahead, left, right, up, down) and eyes closed. The acquisition with the straight-ahead gaze was chosen as the reference position. Left and right optic nerves were segmented on the six acquisitions, and total volumes and maximum amplitude motions were calculated in three dimensions.ResultsMaximum differences were observed while looking left and up, with a median maximum amplitude of 5 and 6 mm [range: 2–7 mm], respectively. These motions induced a position variation of more than 50% of the volume of the optic nerve (compared to the reference position). Greater variations of motion were observed for the anterior portion of the nerve. The gaze position with the fewest variations compared to the reference position was eyes closed.ConclusionOptic nerve positions vary significantly due to the gaze direction, especially for the anterior portion of the nerve. These variations should be taken into account for the treatment of small intraorbital tumors involving the anterior third of the optic nerve.     

Incidence,characteristics, management and outcome of patients with follicular lymphoma with tumor epidural compression,a study on 22 cases

PurposeFollicular lymphoma (FL) is one of the most common lymphoma. Occasionally, FL is associated with tumoral epidural compression and management of these patients remain poorly codified. This study aims to report incidence, clinical characteristics, management and outcomes of patients with FL and tumoral epidural compression.Material and methodsObservational, retrospective cohort study of adult patients with FL and epidural tumor compression, treated in a French Institute over the last 20 years (2000–2021).ResultsBetween 2000 and 2021, 1382 patients with FL were followed by the haematological department. Of them, 22 (1.6%) patients (16 men and 6 women) had follicular lymphoma with epidural tumor compression. At epidural tumor compression occurrence, 8/22 (36%) patients had a neurological clinical deficit (motor, sensory or sphincter function) and 14/22 (64%) had tumor pain. All patients were treated with immuno-chemotherapy; the main regimen being used was R-CHOP plus high dose IV methotrexate in 16/22 (73%) patients. Radiotherapy for tumor epidural compression was performed in 19/22 (86%) patients. With a median follow-up of 60 months (range = [1–216]), 5 year local tumor relapse free survival was achieved in 65% (95% CI 47–90%) of patients. The median PFS was of 36 months (95% CI 24–NA) and 5 years OS estimate was 79% (95% CI 62–100%). Two patients developed a relapse at a second epidural site.ConclusionFL with tumoral epidural compression reached 1.6% of all FL patients. Management based on immuno-chemotherapy with radiotherapy appeared to produce comparable outcomes with the general FL population.     

Brachytherapy: An emblematic example of extreme hypofractionated regimen

In order to provide more convenient irradiation regimens for patient comfort, radiation facility organization and health expenses, new hypofractionated protocols have been evaluated. Moderately (dose/fraction: 2.3 to 3 Gy), then ultra (dose/fraction: 5.2 to 6.1 Gy) hypofractionated irradiations were first validated. The current question is: is it possible to go forward using extreme hypofractionated regimens (EHR) based on 1 to 3 fractions. Different irradiation techniques are under investigation. However, brachytherapy remains the smartest way to deliver a high dose in a small volume. We report prospective and retrospective study results which evaluated EHR for breast and prostate brachytherapy. While oncological outcome and toxicity profile appear extremely encouraging for low-risk breast cancer after a 1 to 4 fractions (6.25 to 20 Gy/fraction), the use of a single fraction of 19 to 23 Gy appears debatable for prostate cancer. Brachytherapy represents an emblematic example of EHR but longer follow-up and more mature results are awaited in order to specify the right indications and refine the EQD2 calculation method including new biological and technical factors.     

Decline in CA19-9 during chemotherapy predicts survival in four independent cohorts of patients with inoperable bile duct cancer

BackgroundCarbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer.MethodsConsecutive patients with inoperable bile duct cancer treated at a University Hospital were retrospectively included in an investigational cohort (n = 212). Three validation cohorts were established including patients 1) participating in phase I/II trials at a Danish Hospital (n = 71), 2) identified retrospectively in a Canadian cohort (n = 196) and 3) randomized in the ABC-02 trial (n = 410). Patients with a baseline CA19-9 and at least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were included. Multivariate Cox regression analyses were performed.ResultsPatients meeting the criteria to be included were 54 in the investigational cohort and 34, 68 and 148 in the three validation sets, respectively. Multivariate analysis included radiological response, performance status, bilirubin, gender, site of cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of 0.60 (95%CI: 0.44-0.80, p = 0.0005) for death in CA19-9 responders was reached in the investigational cohort. The predictive value of CA 19-9 response was confirmed in all three validation cohorts.ConclusionsCA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets.     

Outcomes Following SBRT vs. IMRT and 3DCRT for Older Patients with Stage IIA Node-Negative Non-Small Cell Lung Cancer > 5 cm

BackgroundTo describe outcomes and compare the effectiveness of stereotactic body radiotherapy (SBRT) versus 3-dimensional conformal radiotherapy (3DCRT) or intensity-modulated radiotherapy (IMRT) in patients with stage IIA lymph node-negative (N0) non-small cell lung cancer (NSCLC) tumors > 5 cm.MethodsWe used the SEER-Medicare database (2005-2015) to identify patients > 65 years with stage IIA (AJCC TNM7) N0 NSCLC > 5 cm tumors who were treated with SBRT, IMRT, and 3DCRT. We used propensity score methods with inverse probability weighting to compare lung cancer-specific survival (LCSS), overall survival (OS), and toxicity.ResultsOf 584 patients, 88 (15%), 140 (24%), and 356 (61%) underwent SBRT, IMRT, and 3DCRT, respectively. The SBRT group was older (P = .004), had more comorbidities (P = .02), smaller tumors (P = .03), and more adenocarcinomas (P < .0001). We found a trend towards higher median unadjusted OS with SBRT compared to IMRT and 3DCRT (19 vs. 13 and 14 months, respectively, P = .37). In our propensity score-adjusted analyses, SBRT was significantly associated with better OS and LCSS compared to IMRT (HR_OS: 0.78, 95% CI: 0.68-0.89, HR_LCSS: 0.70, 95% CI: 0.60-0.81) and 3DCRT (HR_OS: 0.81, 95% CI: 0.72-0.93, HR_LCSS: 0.80, 95% CI: 0.68-0.93). SBRT-treated patients also had lower overall adjusted complication rates compared to IMRT (OR: 0.74, 95% CI: 0.55-0.99) and 3DCRT (OR: 0.53, 95% CI: 0.40-0.71).ConclusionFor patients with NSCLC tumors > 5 cm, SBRT trends towards fewer toxicities and improved survival compared to other forms of radiotherapy. Our findings support SBRT as an appropriate treatment strategy for older patients with larger inoperable NSCLC tumors.     

Long-term outcomes of deceased donor liver transplantation in hepatocellular carcinoma patients with portal vein tumor thrombus: A multicenter study

BackgroundThe incidence of portal vein tumor thrombus (PVTT) has been reported to be as high as approximately 10%–40% in patients with hepatocellular carcinoma (HCC). The long-term prognosis of deceased donor liver transplantation (DDLT) in HCC patients with PVTT remains unknown.MethodsData of 961 HCC patients who underwent DDLT between 2015 and 2018 in six centers were analyzed. Based on the Milan criteria (MC) and Cheng's classification of PVTT, the patients were divided into 4 groups: within MC, beyond MC without PVTT, type 1 PVTT, and type 2 PVTT groups.Results489 (50.9%) were within the MC, 296 (30.8%) beyond the MC but without PVTT, 83 (8.6%) type 1 PVTT, and 93 (9.7%) type 2 PVTT. Kaplan-Meier analysis showed that type 1 or 2 PVTT patients with alpha-fetoprotein (AFP) ≤ 100 ng/mL had overall survival (OS) similar to that of patients within the MC (P = 0.957), and superior OS (P = 0.003 and 0.009) and recurrence-free survival (RFS) (P = 0.038 and <0.001) than those of patients beyond the MC and PVTT patients with AFP > 100 ng/mL. Multivariable Cox-regression analysis identified type 1 and 2 PVTT to be independent risk factor for RFS [hazard ratio (HR) 1.523 95% confidence interval (CI) 1.162–1.997, P = 0.002], but not for OS (HR 1.283, 95%CI 0.922–1.786, P = 0.139).ConclusionHCC patients with type 1 or 2 PVTT may be acceptable candidates for DDLT. To achieve better outcomes, preoperative AFP levels should be seriously considered when selecting patients with PVTT for DDLT.     

Comparing Prothrombin induced by vitamin K absence-II (PIVKA-II) with the oncofetal proteins Glypican-3, Alpha feto protein and Carcinoembryonic antigen in diagnosing hepatocellular carcinoma among Egyptian patients

BackgroundHepatocellular carcinoma (HCC) is usually asymptomatic in the early stage and does not show elevated alpha-feto protein (AFP). AFP shows 60–80% sensitivity in diagnosing HCC.Glypican3 (GPC-3) is an oncofetal protein that is only detected in HCC cells but not in benign liver tissues, while Carcinoembryonic antigen (CEA) is expressed in various neoplasms including HCC. Although, it is not specific for HCC.Prothrombin induced by vitamin K absence-II (PIVKA-II) is an abnormal prothrombin protein that is increased in the serum of HCC patients. It has higher sensitivity and specificity compared to AFP.The aim of this study is to compare the clinical utility of PIVKA-II with GPC-3, AFP and CEA in diagnosing HCC.Patients and methodsThis study included 40 patients with HCC, 10 patients with cirrhosis as a benign control group, and 10 apparently healthy volunteers as normal controls.Serum samples were subjected to routine laboratory investigations, measurement of CEA, AFP using MEIA technique (Axsym), glypican3, and PIVKA-II using ELISA technique in the sera of all patients and controls.ResultsAll markers showed the highest results in the HCC group. Higher concentrations of PIVKA-II were detected in patients with splenomegaly, and in tumors with size (>3 cm). Combination of Glypican-3 and PIVKA-II showed the highest sensitivity, while GPC-3 alone and combination of GPC-3 and AFP showed the highest specificity to differentiate HCC from liver cirrhosis and normal controls. GPC-3, PIVKAII, and combination of both showed the highest sensitivity, while GPC-3 alone showed the highest specificity to differentiate HCC from liver cirrhosis.ConclusionGlypican-3 is the only oncofetal antigen that showed comparable high diagnostic accuracy as PIVKA-II in diagnosing HCC among Egyptian patients.     

Impact of ABO-incompatibility on hepatocellular carcinoma recurrence after living donor liver transplantation

BackgroundABO-incompatible (ABO-I) living donor liver transplantation (LDLT) has been reported to have acceptable outcomes in the era of rituximab-based prophylaxis. However, the outcomes of ABO-I LDLT for hepatocellular carcinoma (HCC) remain to be elucidated. This study aimed to clarify the impact of ABO-Incompatibility on oncologic outcomes of LDLT for HCC.MethodsPatients with HCC who underwent ABO-I LDLT were randomly matched by 1:2 ratio to those who underwent ABO-compatible (ABO-C) LDLT according to propensity score. HCC recurrence and patient survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsBetween January 2012 and December 2015, a total of 160 patients underwent LDLT for HCC confirmed by pathology analysis of liver explants. Thirty-nine consecutive patients underwent ABO-I LDLT for HCC, and 78 ABO-C LDLT patients were selected by propensity score matching, which made no significant difference between the two groups in baseline, perioperative, and tumor characteristics. The 1-, 3-, and 5-year recurrence-free survival rates in the ABO-I and ABO-C LDLT groups were 76.9%, 68.5%, 63.6% and 74.4%, 70.5%, 70.5%, respectively (p = 0.77). The site distribution of initial recurrence showed no significant difference between the two groups. The overall survival rates over the same period in the ABO-I and ABO-C LDLT groups were 82.1%, 73.5%, 73.5% and 92.2%, 80.3%, 80.3%, respectively (p = 0.34).ConclusionsABO-I LDLT, having no adverse impact on oncological outcomes, can be a feasible transplant option for HCC.     

A novel multipurpose device for guided knee motion and loading during dynamic magnetic resonance imaging

IntroductionThis work aimed to develop a novel multipurpose device for guided knee flexion-extension, both passively using a motorized pneumatic system and actively (muscle-driven) with the joint unloaded or loaded during dynamic MRI. Secondary objectives were to characterize the participant experience during device use, and present preliminary dynamic MRI data to demonstrate the different device capabilities.Material and methodsSelf-reported outcomes were used to characterize the pain, physical exertion and discomfort levels experienced by 10 healthy male participants during four different active knee motion and loading protocols using the novel device. Knee angular data were recorded during the protocols to determine the maximum knee range of motion achievable. Dynamic MRI was acquired for three healthy volunteers during passive, unloaded knee motion using 2D Cartesian TSE, 2D radial GRE and 3D UTE sequences; and during active, unloaded and loaded knee motion using 2D radial GRE imaging. Because of the different MRI sequences used, spatial resolution was inherently lower for active knee motion than for passive motion acquisitions.ResultsDepending on the protocol, some participants reported slight pain, mild discomfort and varying levels of physical exertion. On average, participants achieved ～40° of knee flexion; loaded conditions can create knee moments up to 27 Nm. High quality imaging data were obtained during different motion and loading conditions. Dynamic 3D data allowed to retrospectively extract arbitrarily oriented slices.ConclusionA novel multipurpose device for guided, physiologically relevant knee motion and loading during dynamic MRI was developed. Device use was well tolerated and suitable for acquiring high quality images during different motion and loading conditions. Different bone positions between loaded and unloaded conditions were likely due to out-of-plane motion, particularly because image registration was not performed. Ultimately, this device could be used to advance our understanding of physiological and pathological joint mechanics.     

Albumin-bilirubin (ALBI) grade-based nomogram to predict tumor recurrence in patients with hepatocellular carcinoma

BackgroundTumor recurrence after curative resection is common in hepatocellular carcinoma (HCC), but large-scale long-term prediction on an individual basis has seldom been reported. We aimed to construct an albumin-bilirubin (ALBI) grade-based nomogram to predict tumor recurrence in patients with HCC undergoing surgical resection.MethodsA total 1038 patients with newly diagnosed HCC undergoing curative resection between 2002 and 2016 were enrolled. Baseline characteristics, tumor status and severity of liver functional reserve were collected. The Cox proportional hazards model was used to predict tumor recurrence and construct the nomogram. The performance of the nomogram was evaluated by the discrimination and calibration tests.ResultsAfter a mean follow up time of 30 months, 510 (49%) patients developed tumor recurrence. The cumulative recurrence-free survival at 1, 3, 5, and 10 years were 79%, 51%, 38% and 26%, respectively. In the Cox multivariate model, ALBI grade 2–3, multiple tumors, tumor size equal or large than 2 cm, serum ɑ-fetoprotein level equal or greater than 20 ng/ml and total tumor volume equal or larger than 227 cm³ were independent risk factors associated with tumor recurrence. A nomogram was constructed based on these five variables. Internal validation with 10,380 bootstrapped sample sets had a good concordance of 0.607 (95% of confidence interval: 0.587–0.627). The calibration plots for 1-, 3- and 5-year recurrence-free survival well matched the idealized 45-degree line.ConclusionsALBI is a feasible marker for tumor recurrence. This easy-to-use ALBI grade-based nomogram may predict tumor recurrence for individual HCC patient undergoing surgical resection.     

Real-world role of performance status in surgical resection for hepatocellular carcinoma: A multicenter study

BackgroundThe Barcelona Clinic Liver Cancer (BCLC) categorizes a patient with performance status (PS)-1 as advanced stage of hepatocellular carcinoma (HCC) and surgical resection is not recommended. In real-world clinical practice, PS-1 is often not a contraindication to surgery for HCC. The aim of current study was to define the impact of PS on the surgical outcomes of patients undergoing liver resection for HCC.Methods1,531 consecutive patients who underwent a curative-intent resection of HCC between 2005 and 2015 were identified using a multi-institutional database. After categorizing patients into PS-0 (n = 836) versus PS-1 (n = 695), perioperative mortality and morbidity, overall survival (OS) and recurrence-free survival (RFS) were compared.ResultsOverall perioperative mortality and major morbidity among patients with PS-0 (n = 836) and PS-1 (n = 695) were similar (1.4% vs. 1.6%, P = 0.525 and 9.7% vs. 10.2%, P = 0.732, respectively). In contrast, median OS and RFS was worse among patients who had PS-1 versus PS-0 (34.0 vs. 107.6 months, and 20.5 vs. 60.6 months, both P < 0.001, respectively). On multivariable Cox-regression analyses, PS-1 was independently associated with worse OS (HR: 1.301, 95% CI: 1.111–1.523, P < 0.001) and RFS (HR: 1.184, 95% CI: 1.034–1.358, P = 0.007).ConclusionsPatients with PS-1 versus PS-0 had comparable perioperative outcomes. However, patients with PS-1 had worse long-term outcomes as PS-1 was independently associated with worse OS and RFS. Routine exclusion of HCC patients with PS-1 from surgical resection as recommended by the BCLC guidelines is not warranted.     

Clinical presentation and prognosis of adenosquamous carcinoma of the pancreas – Matched-pair analysis with pancreatic ductal adenocarcinoma

IntroductionAdenosquamous carcinoma of the pancreas (ASCP) is a rare subtype of pancreatic adenocarcinoma. The aim of this study was to investigate the characteristics and outcomes of ASCP in comparison to pancreatic ductal adenocarcinoma (PDAC).Materials and methodsAll patients with ASCP treated between December 2001 and December 2017 were identified from a prospective database. Clinicopathological and follow-up data were analyzed. A nested case-control-study with matched-pair analysis was performed to compare overall survival of ASCP and PDAC.ResultsOf 4009 patients undergoing surgery for pancreatic adenocarcinoma 91 patients had ASCP. Compared to PDAC ASCP were larger (4.0 vs. 3.2 cm; p < 0.0001), more frequently involved lymph nodes (88% vs. 78%; p = 0.0216), more frequently showed poor differentiation (G3: 79% vs. 36%; p < 0.0001) and more frequently were located in the pancreatic tail (19% vs. 10%; p = 0.0179). Overall median post-resection-survival was shorter in ASCP (10.8 vs. 20.5 months in PDAC; p = 0.0085), but 5-year survival rates were comparable (18.2% vs. 17.5%). After matching for the unevenly distributed prognostic factors survival after resection of ASCP and PDAC was comparable (p = 0.8301). Localization in the head or several parts of the pancreas, high CA 19-9 levels, and M1 disease were independent predictors of survival in patients with ASCP.ConclusionASCP is more aggressive with poorer differentiation and higher rates of lymph node metastases compared to PDAC. In spite of a shorter median survival, 5-year survival rates after surgical resection of about 18% can be expected in ASCP and support resection as part of a multimodal therapy as the treatment of choice in this rare cancer.     

Association of primary tumor location with long-term oncological prognosis following hepatectomy for hepatocellular carcinoma:A multicenter propensity score matching analysis

PurposeThere is a striking laterality in the site of hepatocellular carcinoma (HCC), with a strong predominance for the right side; however, the impact of primary tumor location on long-term prognosis after hepatectomy of HCC remains unclear. This study aimed to investigate the effect of primary tumor location on long-term oncological prognosis after hepatectomy for HCC.Patients and methodsData of consecutive patients undergoing curative hepatectomy for HCC between 2008 and 2017 were analyzed. Overall survival (OS) and recurrence-free survival (RFS) of left-sided HCC (LS group) and right-sided HCC (RS group) were compared by using propensity score matching (PSM) analysis. COX regression analysis was performed to assess the adjusted effect of tumor location on long-term oncological prognosis.ResultsOf the 2799 included patients, 707 (25.3%) and 2092 (74.7%) were in the LS and RS groups, respectively. Using PSM analysis, 650 matched pairs of patients were created. In the PSM cohort, median OS (66.0 vs. 72.0 months, P = 0.001) and RFS (28.0 vs. 51.0 months, P < 0.001) were worse among patients in the LS group compared to individuals in the RS group. After further adjustment for other confounders using multivariable COX regression analyses, HCC located on the left side remained independently associated with worse OS and RFS.ConclusionTumors located on the left side are associated with poorer OS and RFS after hepatectomy for HCC. Careful surgical options selection and frequent follow-up to improve long-term survival may be justified for HCC patients with left-sided primary tumors.