Ergonomics in Craniofacial Surgery: Can We Do Better? A Quality Improvement Study.

OBJECTIVE: Many plastic surgeons experience musculoskeletal strain and injury from poor ergonomics during surgery. This is associated with reduced performance, shortened careers, and decreased quality of life. This study compared the ergonomics of the conventional operating table headrest and the Mayfield headrest in craniofacial surgery. METHODS: A prospective cohort study of patients undergoing craniofacial operations between November 20, 2022 and April 26, 2023, within a single craniofacial surgeon's practice. The authors obtained data on the total duration of the operation and Rapid Entire Body Assessment (REBA) scores for the primary surgeon and assistant. RESULTS: Four operations (mean: 147 ± 60.9 min) were included in the regular headrest group, and 8 in the Mayfield headrest group (mean: 61±53.4 min). Four hundred fifty-five regular headrest time points and 851 Mayfield time points were recorded. Eight hundred thirty-five regular headrest time points and 538 Mayfield time points were recorded. The mean REBA score for the regular headrest was 5.79 ± 1.9, which was higher than the Mayfield (5.01 ± 2.0; P < 0.0001). Subgroup analysis showed the mean REBA score for the primary surgeon (5.89 ± 2.0) was higher than the assist (5.48 ± 1.6) in the regular headrest group (P < 0.0001), whereas the converse was true for the Mayfield headrest (primary surgeon: 4.67 ± 1.8, assist: 5.65 ± 2.15, P < 0.0001). CONCLUSIONS: Ergonomic scores were better using the Mayfield headrest than the regular headrest. The primary surgeon scored better with the Mayfield headrest, whereas the assists had better scores with the regular headrest.

Vascularized versus non-vascularized bone grafting for scaphoid nonunion without avascular necrosis: a randomized clinical trial.

In this clinical trial, patients were randomized to receive a pedicled vascularized bone graft, based on the 1,2-intercompartmental supraretinacular artery, or a non-vascularized iliac crest graft. Fixation was done with K-wires. Union and time to union were assessed using CT scans at regular intervals. Twenty-three patients received a vascularized graft, and 22 received a non-vascularized graft. Thirty-eight patients were available for union assessment and 23 for clinical measurements. There were no significant differences in union incidence, time to union, incidence of complications, patient-reported outcome scores, or wrist mobility and grip strength at final follow-up between the treatment groups. Smokers were 60% less likely to achieve union, independent of graft type. When controlling for smoking, patients receiving a vascularized graft were 72% more likely to achieve union. Given our small sample size, results should be interpreted with caution.Level of evidence: I.

Outcomes of Immediate Alloplastic Breast Reconstruction in Patients Receiving Post-Mastectomy Radiotherapy.

Background: Immediate alloplastic breast reconstruction is traditionally avoided in patients who require post-mastectomy radiation therapy (PMRT). However, a subset of patients who undergo alloplastic reconstruction may unpredictably require adjuvant radiation. The purpose of this study was to compare outcomes and complications in patients at our institution who had undergone immediate alloplastic breast reconstruction and received PMRT to either the permanent implant or temporary tissue expander. Materials and Methods: A retrospective cohort study was performed looking at patients who underwent immediate alloplastic breast reconstruction over a 10-year period (2009-2019) at our regional breast centre. All patients who underwent immediate alloplastic breast reconstruction and had PMRT were included in the study. Major (wound dehiscence with device exposure, or reconstructive failure) and minor (infection, capsular contracture, revision surgery) complication rates between those patients receiving radiation to a tissue expander versus implant were compared using Fisher exact test (P < .05). Results: Six-hundred ninety-two patients were identified, and 43 patients met inclusion criteria. Of this group, 29 received PMRT to implants and 14 received PMRT to tissue expanders. Complication rates were similar between groups for superficial wound infection (3.4% vs 7.1%), periprosthetic infection (3.4% vs 7.1%), capsular contracture (41.4% vs 21.4%), revision surgery for aesthetics (41.4% vs 21.4%), wound dehiscence and device exposure (3.4% vs 21.3%), and reconstructive failure (10.3% vs 6.7%). Total complication rates were similar between groups (51.7% vs 42.9%). Discussion: Overall 6.4% of patients who underwent immediate alloplastic breast reconstruction required PMRT over a 10-year period. Complication rates for infection, capsular contracture, revision surgery, wound dehiscence and device exposure, and reconstructive failure were similar between both groups. Total complication rates were similar between groups. This information will help to inform decision-making regarding immediate alloplastic reconstruction and expected complications when PMRT is needed.

Historique: D'habitude, on évite la reconstruction mammaire alloplastique immédiate chez les patientes qui ont besoin d'une radiothérapie après la mastectomie (RTAM). Toutefois, un sous-groupe de patientes peut avoir besoin de radiation adjuvante non planifiée. La présente étude visait à comparer les résultats cliniques et les complications chez les patientes de l'établissement des chercheurs, après une reconstruction mammaire alloplastique immédiate et une RTAM sur l'implant permanent ou les expanseurs tissulaires permanents. Matériaux et méthodologie: Les chercheurs ont procédé à une étude de cohorte rétrospective sur une période de dix ans (2009 à 2019) auprès de patientes qui avaient subi une reconstruction mammaire alloplastique immédiate à leur centre régional de traitement du cancer du sein. Toutes les patientes qui avaient subi une telle reconstruction et une RTAM en ont fait partie. Au moyen du test exact de Fisher (p < 0,05), les chercheurs ont comparé les complications majeures (déhiscence des plaies et exposition du dispositif ou échec de la reconstruction) et mineures (infection, contracture capsulaire, chirurgie de reprise) entre les patientes recevant une radiation sur les expanseurs tissulaires et sur l'implant, respectivement. Résultats: Les chercheurs ont extrait 692 patientes, dont 43 respectaient les critères d'inclusion. De ce groupe, 29 ont reçu une RTAM sur les implants et 14, sur les expanseurs tissulaires. Le taux de complication était semblable entre les groupes pour ce qui était de l'infection superficielle de la plaie (3,4 % par rapport à 7,1 %), de l'infection périprosthétique (3,4 % par rapport à 7,1 %), de la contracture capsulaire (41,4 % par rapport à 21,4 %), de la reprise de l'intervention pour des raisons esthétiques (41,4 % par rapport à 21,4 %), de la déhiscence de la plaie et de l'exposition du dispositif (3,4 % par rapport à 21,3 %) et de l'échec de la reconstruction (10,3 % par rapport à 6,7 %). Le taux total de complications était semblable entre les groupes (51,7 % par rapport à 42,9 %). Discussion: Dans l'ensemble, 6,4 % des patients qui ont subi une reconstruction mammaire alloplastique immédiate ont eu besoin d'une RTAM sur une période de dix ans. Le taux de complications d'infection, de contracture capsulaire, de chirurgie de reprise, de déhiscence de la plaie, d'exposition du dispositif et d'échec de la reconstruction était semblable dans les deux groupes, de même que le taux total de complications. Ces données contribueront à éclairer la décision de procéder à une reconstruction alloplastique immédiate et à évaluer les complications possibles en cas de RTAM.

How Much Scaphoid Can be Safely Resected? A Biomechanical Analysis of the Effects of Distal Scaphoid Resection.

BACKGROUND: Resection of the distal pole of the scaphoid has been advocated as a simple alternative to other wrist salvage procedures for scaphoid nonunion advanced collapse and scaphotrapezio-trapezoid arthritis. However, the extent of scaphoid that may be resected without adversely affecting carpal kinematics has never been clearly defined. METHODS: Seven cadaveric upper extremities were tested in a custom motion wrist simulator. A 3-stage sequential sectioning of the distal scaphoid protocol was performed in 25% increments then cyclic active wrist flexion-extension and dart thrower's motion trials were recorded. RESULTS: The extent of distal scaphoid resection had no effect on overall wrist range of motion. The lunate assumed a more extended position following resection of the distal scaphoid compared to intact. At 25%, 50%, and 75% of distal scaphoid resection, the lunate extended to 13.32° ± 9.4°, 23.43° ± 7.5°, and 15.81° ± 16.9°, respectively. The capitate migrated proximally with 25% and 50% distal scaphoidectomy, and proximally and radially with 75% of the scaphoid resected. Resection of 75% of the scaphoid resulted in unstable wrist kinematics. CONCLUSIONS: Resection of up to 25% of the distal scaphoid did not significantly influence carpal kinematics and induced mild lunate extension deformity. Resection of 50% of the scaphoid induced further and potentially clinically significant lunate extension and dorsal intercalated segment instability. Further removal of 75% of the distal scaphoid induced capitate migration radially and unpredictable wrist kinematics. Consequently, removal of over 25% of the scaphoid should be avoided or supplemented with partial wrist fusion.

Development of an In Vitro Swan Neck Deformity Biomechanical Model.

BACKGROUND: Injury to the finger's extensor mechanism is a common cause of swan neck deformity (SND). Progression of extensor and flexor tendon imbalance negatively affects laxity of the volar plate, resulting in the inhibition of proper finger motion. The complexity of finger anatomy, however, makes understanding the pathomechanics of these deformities challenging. Therefore, development of an SND model is imperative to understand its influence on finger biomechanics and to provide an in vitro model to evaluate the various treatment options. METHODS: The index, middle, and ring fingers from 8 cadaveric specimens were used in an in vitro active motion simulator to replicate finger flexion/extension. An SND model was developed through sectioning of the terminal extensor tendon at the distal insertion (creating a mallet finger) and transverse retinacular ligament (TRL). A strain gauge inserted under the volar plate measured laxity of the plate, and electromagnetic trackers recorded proximal interphalangeal joint (PIPJ) angles. RESULTS: Strain in the volar plate increased progressively with creation of the mallet and SND conditions (P = .015). Although not statistically significant, the mallet finger condition accounted for 26% of the increase, whereas sectioning of the TRL accounted for 74% (P = .031). As predicted, PIPJ hyperextension was not detectable by joint angle measurement; however, the PIPJ angle had a strong positive correlation with volar plate strain (R2 = 1.0, P < .001). CONCLUSION: Volar plate strain measurement, in an in vitro model, can detect an induced SND. Moreover, as a surrogate for PIPJ hyperextension, volar plate strain may be useful to evaluate the time-zero effectiveness of various surgical interventions.

The Impact of Scaphoid Malunion on Carpal Motion: An In-Vitro Analysis.

Background: The clinical significance of scaphoid malunion is debated and its effect on wrist kinematics is poorly understood. Alterations to scaphoid morphology in other pathologies result in significant sequelae and arthrosis. By understanding the impact of scaphoid malunion on carpal kinematics, better insight can be garnered to inform models of wrist motion and clinical treatment of this injury. Methods: Seven cadaveric upper extremities underwent active wrist flexion and extension in a custom motion wrist simulator with scaphoid kinematics being captured with respect to the distal radius. A three-stage protocol of progressive simulated malunion severity was performed [intact, 10° malunion (Mal 10°), 20° malunion (Mal 20°)] with data analyzed from 45° wrist extension to 45° wrist flexion. Scaphoid malunions were modelled by creating successive volar wedge osteotomies and reducing the resultant scaphoid fragments with two 0.062" Kirshner wires. Motion of the scaphoid, lunate, trapezium-trapezoid was recorded using optical trackers. Results: Increasing scaphoid malunion severity did not significantly affect scaphoid or trapezium-trapezoid motion (p > 0.05); however, it did significantly alter lunate motion (p < 0.001). Increasing malunion severity resulted in progressive lunate extension across wrist motion (Intact - Mal 10°: mean difference (mean dif.) = 7.1° ± 1.6, p < 0.05; Intact - Mal 20°: mean dif. = 10.2° ± 2.0, p < 0.05). Conclusions: In this in-vitro model, increasing scaphoid malunion severity was associated with progressive extension of the lunate in all wrist positions. The clinical significance of this motion change is yet to be elucidated, but this model serves as a basis for understanding the kinematic consequences of scaphoid malunion deformities.

The effect of four-corner fusion and proximal row carpectomy on uniplanar and multiplanar wrist motion: A biomechanical study.

PURPOSE: To compare changes in wrist kinematics after scaphoidectomy and four-corner fusion (4CF), and proximal row carpectomy (PRC). METHODS: Six cadaveric specimens underwent flexion-extension, radial-ulnar deviation and circumduction in an active motion wrist simulator. Native state, "anatomic 4CF", "radial 4CF", and PRC were compared. RESULTS: Radial 4CF reduced wrist extension, while PRC reduced radial deviation. Fusion groups had similar motion profiles. 44%, 41%, and 32% of native circumduction was maintained in PRC, anatomic, and radial 4CF. CONCLUSIONS: Both fusion positions resulted in comparable motion outcomes. Anatomic 4CF was restricted in wrist extension compared to PRC but provided favourable radial deviation.

Use of Thermoplastic Rings Following Venting of Flexor Tendon Pulleys: A Biomechanical Analysis.

PURPOSE: Normal digital flexion relies on flexor tendon pulleys to convert linear muscular force to angular digital motion. However, there is a growing trend to vent them partially during flexor tendon repair. The objective of this study was to examine the effects of a thermoplastic ring, acting as an external pulley, on flexor tendon biomechanics and finger range of motion (ROM) after pulley venting. METHODS: We tested 15 cadaveric digits using an in vitro active finger motion simulator. We measured loads induced by flexor digitorum superficialis (FDS) and flexor digitorum profundus (FDP) as well as joint ROM with sequential sectioning of the A2, A3, and A4 pulleys compared with an intact pulley condition. At each stage, external thermoplastic pulley rings were applied snugly over the proximal and middle phalanges to recreate A2 and A4 function, respectively. RESULTS: After complete venting of the A2, A3, and A4 pulleys, proximal interphalangeal joint ROM significantly decreased by 13.4° ± 2.7° and distal interphalangeal joint ROM decreased by 15.8° ± 2.1°. Application of external rings over the proximal and middle phalanx resulted in a residual ROM decrease of 8.3° ± 1.9° at the proximal interphalangeal joint and 7.9° ± 2.1° at the distal interphalangeal joint, nearly restoring ROM. Similarly, complete pulley venting resulted in reduced FDS load by 37% and FDP load by 50% compared with intact pulleys. After application of external rings, loads were restored almost to normal, with a 9% reduction for FDS load and 9% reduction for FDP load compared with intact pulleys. CONCLUSIONS: The application of thermoplastic rings acting as external pulleys is an effective, noninvasive, and reproducible approach to restore flexor tendon biomechanics and digit ROM after pulley venting. CLINICAL RELEVANCE: Thermoplastic rings may be a useful therapeutic adjunct in restoring joint ROM and flexor tendon loads after surgical venting of the pulleys.

Regional Wait Times for Patients With Nonmelanoma Skin Cancer in Southwestern Ontario.

BACKGROUND: Nonmelanoma skin cancer (NMSC) affects many Canadians. Although morbidity and mortality are rare, the burden to patients and the health-care system is significant. This study aims to evaluate current plastic surgery wait times and care pathways for patients with NMSC in Southwestern Ontario. METHODS: A retrospective chart review of 225 patients treated in Ontario from 2015 to 2018 was conducted. Inclusion criteria included patients with an NMSC managed with surgical excision. Referral information was compared. Primary outcomes were wait times: from referral to consultation, referral to excision, and consultation to excision. Data were analyzed using Student t test with equal variance. RESULTS: One-hundred forty-three patients were included from the academic cohort and 82 from the community cohort. Referrals to academic and community surgeons included lesion location (90% and 97.6%, respectively), but less frequently included size (18% and 29.2%, respectively). Most referrals to academic surgeons included biopsy results (78.6%), as opposed to community referrals (25.6%). Patients in the academic cohort waited 15.3 ± 12.7 weeks from referral to consultation, and 15.7 ± 13 weeks from referral to excision. Patients from the community cohort waited significantly shorter periods of 4.9 ± 3.1 (P < .001) and 11.7 ± 9.9 weeks (P = .016), respectively. However, patients of the academic cohort waited 2.4 ± 7.1 weeks from consultation to excision, while patients in the community cohort waited 6.7 ± 9.6 weeks (P < .001). Rates of negative peripheral margins on pathology were similar between groups, at 89.5% of the academic cohort and 88.9% of the community cohort. Deep margins were positive 5.7% of the time at the academic sites and 6.2% of the time in the community. CONCLUSIONS: Patients referred to academic centres waited significantly longer periods of time in several parameters compared to those referred to a community surgeon. However, academic surgeons often had expedited consultation-to-excision time frame. This study provides important data for future quality improvement initiatives in NMSC care.

HISTORIQUE: De nombreux Canadiens ont un cancer cutané non mélanome (CCNM). Bien que la morbidité et la mortalité soient rares, le fardeau est important pour les patients et le système de santé. La présente étude a été conçue pour évaluer les temps d'attente et les trajectoires de soins en chirurgie plastique pour les patients du sud-ouest de l'Ontario ayant un CCNM. MÉTHODOLOGIE: Les chercheurs ont réalisé une analyse rétrospective des dossiers de 225 patients traités de 2015 à 2018 en Ontario. Un CCNM traité par excision chirurgicale faisait partie des critères d'inclusion. Les chercheurs ont comparé les données d'adressage vers la chirurgie. Les résultats cliniques primaires étaient les temps d'attente entre l'adressage et la consultation, entre l'adressage et l'excision ainsi qu'entre la consultation et l'excision. Les chercheurs ont analysé les données au moyen du test de Student de variance égale. RÉSULTATS: Au total, 143 patients ont fait partie de la cohorte universitaire et 82, de la cohorte communautaire. L'adressage vers des chirurgiens universitaires ou communautaires découlait du siège de la lésion (90 % et 97,6 %, respectivement) et, à une moindre fréquence, de sa dimension (18,6 % et 29,2 %, respectivement). La plupart des adressages vers des chirurgiens universitaires incluaient les résultats de biopsies (78,6 %), contrairement à celui vers des chirurgiens communautaires (25,6 %). Les patients de la cohorte universitaire ont attendu 15,3 ± 12,7 semaines entre l'adressage et la consultation, et 15,7 ± 13 semaines entre l'adressage et l'excision. Les patients de la cohorte communautaire ont attendu beaucoup moins longtemps, soit 4,9 ± 3,1 (P < 0,001) et 11,7 ± 9,9 semaines (P = 0,016), respectivement. Cependant, les patients de la cohorte universitaire ont attendu 2,4 ± 7,1 semaines entre la consultation et l'excision, et ceux de la cohorte communautaire, 6,7 ± 9,6 semaines (P < 0,001). À la pathologie, le taux de marges périphériques négatives était semblable entre les groupes, se situant à 89,5 % dans la cohorte universitaire et à 88,9 % dans la cohorte communautaire. Les marges profondes étaient positives dans 5,7 % des cas en milieu universitaire et dans 6,2 % des cas dans la communauté. CONCLUSIONS: Les patients adressés à des centres universitaires attendaient considérablement plus longtemps à l'égard de plusieurs paramètres par rapport à ceux adressés à un chirurgien communautaire. Cependant, les chirurgiens universitaires réduisaient souvent la période entre la consultation et l'excision. La présente étude fournit des données importantes en vue de prochaines initiatives d'amélioration de la qualité des soins du CCNM.

Variation of Grip Strength and Wrist Range of Motion with Forearm Rotation in Healthy Young Volunteers Aged 23 to 30.

Background Grip strength and wrist range of motion (ROM) are important metrics used to evaluate hand rehabilitation and outcomes of wrist interventions. Published normative data on these metrics do not recognize the contribution of forearm rotation. This study aims to identify and quantify variations in grip strength and wrist ROM with forearm rotation in healthy young individuals. Materials and Methods Wrist ROM and grip strength were measured in 30 healthy volunteers aged 23 to 30. Participant demographics, grip strength, and wrist ROM (wrist flexion and extension, ulnar and radial deviation) at three forearm positions (full supination, neutral, and full pronation) were measured using a digital dynamometer and standard goniometers. Data analysis was conducted using a one-way repeated measure ANOVA. Forearm position values were compared using post hoc analysis. Results Grip strength in males was greatest in neutral position (males: nondominant 51.4 kg, dominant 56.1 kg) followed by supination (males: nondominant 46.6 kg, dominant 51.7 kg) and weakest in pronation (males: nondominant 40.1 kg, dominant 42.9 kg). Grip strength in females was similar between supination (nondominant: 26.1 kg, dominant: 28.5 kg) and neutral (nondominant: 27.4 kg, dominant: 29.1 kg) positions, but both were greater than in pronation (nondominant: 22.3 kg, dominant: 24.1 kg). Wrist flexion in males was significantly reduced in supination compared with neutral and pronated positions (nondominant: supination 63.1°, neutral 72.6°, pronation 73.3°; dominant: supination 62.4°, neutral 70.2°, pronation 70.3°), whereas not significant wrist flexion in females was also weaker in supination (supination 74.4°, neutral 79.9°). Wrist extension in males was greater in pronation (supination 64.6°, pronation 69.5°) whereas females showed no significant difference in any of the forearm positions. Ulnar deviation in males did not differ with forearm position, but females demonstrated greater ulnar deviation in supination on the nondominant hand (supination 44.6°, pronation 33.2°). Whereas there was no difference in radial deviation with forearm position in females, it was markedly greater in pronation versus supination on both sides in males (nondominant: supination 16.3°, pronation 24.6°; dominant: supination 15.4°, pronation 23.9°). Conclusion This study characterizes variations in grip strength and wrist ROM in three forearm positions in healthy young individuals. All measurements differed with forearm rotation and were not influenced by hand dominance. These results suggest that wrist ROM and grip strength should be evaluated in different positions of forearm rotation, rather than a fixed position. This has functional implications particularly in patients involved with specialized activities such as sports, instrument-playing, or work-related activities.

Treatment of herpes zoster ophthalmicus: a systematic review and Canadian cost-comparison.

OBJECTIVE: A systematic review and cost comparison were conducted to determine the optimal treatment of active herpes zoster ophthalmicus (HZO) in immunocompetent adults. DESIGN: A literature search of MEDLINE, EMBASE, CINAHL, Cochrane Library, BIOSIS Previews and Web of Science, ClinicalTrials.gov, International Clinical Trials Registry Platform, Networked Digital Library of Theses and Dissertations, and Canadian Health Research Collection was performed. The search period was from January 1990 to March 2017. PARTICIPANTS: Collectively, 516 immunocompetent patients with active HZO treated with oral antivirals were included. METHODS: Randomized controlled trials (RCTs) investigating treatment of active HZO in immunocompetent adults, with one oral acyclovir monotherapy arm, were included. Studies fulfilling inclusion criteria were subjected to quality assessment and data extraction. Provincial drug formularies were consulted to extrapolate cost comparison for investigated treatment regimens. RESULTS: A total of 1515 titles and abstracts and 9 full-text articles were assessed. Three RCTs met the inclusion criteria. Treatment with oral acyclovir (800 mg 5 times daily for 10 days) was superior to placebo in the prevention of ocular manifestations. Oral famciclovir (500 mg 3 times daily for 7 days) and valacyclovir (1000 mg 3 times daily for 7 days) resulted in comparable rates of ocular manifestations relative to oral acyclovir (800 mg 5 times daily for 7 days). According to provincial drug formulary data, famciclovir and valacyclovir are more affordable across Canada with the recommended dosing schedules. CONCLUSIONS: Oral famciclovir and valacyclovir are reasonable alternatives to oral acyclovir for treatment of active HZO in immunocompetent individuals. Their simpler dosing schedules are associated with a cost benefit that is consistent across Canada.

Impact of Interventional Oncology Therapies on Tumor Microenvironment and Strategies to Enhance Their Efficacy.

OBJECTIVE: We provide a brief review of the tumor microenvironment, the impact of six interventional radiology treatments on the tumor microenvironment, and potential methods to improve treatment efficacy. CONCLUSION: Interventional oncology plays a unique role in cancer therapy, contributing to both antitumorigenic and protumorigenic effects.

Sorafenib Increases Tumor Hypoxia in Cervical Cancer Patients Treated With Radiation Therapy: Results of a Phase 1 Clinical Study.

PURPOSE: Preclinical studies have shown that angiogenesis inhibition can improve response to radiation therapy (RT). The purpose of this phase 1 study was to examine the angiogenesis inhibitor sorafenib in patients with cervical cancer receiving radical RT and concurrent cisplatin (RTCT). METHODS AND MATERIALS: Thirteen patients with stage IB to IIIB cervical cancer participated. Sorafenib was administered daily for 7 days before the start of standard RTCT in patients with early-stage, low-risk disease and also during RTCT in patients with high-risk disease. Biomarkers of tumor vascularity, perfusion, and hypoxia were measured at baseline and again after 7 days of sorafenib alone before the start of RTCT. The median follow-up time was 4.5 years. RESULTS: Initial complete response was seen in 12 patients. One patient died without achieving disease control, and 4 experienced recurrent disease. One patient with an extensive, infiltrative tumor experienced pelvic fistulas during treatment. The 4-year actuarial survival was 85%. Late grade 3 gastrointestinal toxicity developed in 4 patients. Sorafenib alone produced a reduction in tumor perfusion/permeability and an increase in hypoxia, which resulted in early closure of the study. CONCLUSIONS: Sorafenib increased tumor hypoxia, raising concern that it might impair rather than improve disease control when added to RTCT.