Frontal plane knee alignment mediates the effect of frontal plane rearfoot motion on knee joint load distribution during walking in people with medial knee osteoarthritis.

OBJECTIVE: To examine the nature of differences in the relationship between frontal plane rearfoot kinematics and knee adduction moment (KAM) magnitudes. DESIGN: Cross-sectional study resulting from a combination of overground walking biomechanics data obtained from participants with medial tibiofemoral osteoarthritis at two separate sites. Statistical models were created to examine the relationship between minimum frontal plane rearfoot angle (negative values = eversion) and different measures of the KAM, including examination of confounding, mediation, and effect modification from knee pain, radiographic disease severity, static rearfoot alignment, and frontal plane knee angle. RESULTS: Bivariable relationships between minimum frontal plane rearfoot angle and the KAM showed consistent negative correlations (r = -0.411 to -0.447), indicating higher KAM magnitudes associated with the rearfoot in a more everted position during stance. However, the nature of this relationship appears to be mainly influenced by frontal plane knee kinematics. Specifically, frontal plane knee angle during gait was found to completely mediate the relationship between minimum frontal plane rearfoot angle and the KAM, and was also an effect modifier in this relationship. No other variable significantly altered the relationship. CONCLUSIONS: While there does appear to be a moderate relationship between frontal plane rearfoot angle and the KAM, any differences in the magnitude of this relationship can likely be explained through an examination of frontal plane knee angle during walking. This finding suggests that interventions derived distal to the knee should account for the effect of frontal plane knee angle to have the desired effect on the KAM.

Osteoarthritis year in review 2019: mechanics.

Mechanics play a critical - but not sole - role in the pathogenesis of osteoarthritis, and recent research has highlighted how mechanical constructs are relevant at the cellular, joint, and whole-body level related to osteoarthritis outcomes. This review examined papers from April 2018 to April 2019 that reported on the role of mechanics in osteoarthritis etiology, with a particular emphasis on studies that focused on the interaction between movement and tissue biomechanics with other clinical outcomes relevant to the pathophysiology of osteoarthritis. Studies were grouped by themes that were particularly prevalent from the past year. Results of the search highlighted the large exposure of knee-related research relative to other body areas, as well as studies utilizing laboratory-based motion capture technology. New research from this past year highlighted the important role that rate of exerted loads and rate of muscle force development - rather than simply force capacity (strength) - have in OA etiology and treatment. Further, the role of muscle activation patterns in functional and structural aspects of joint health has received much interest, though findings remain equivocal. Finally, new research has identified potential mechanical outcome measures that may be related to osteoarthritis disease progression. Future research should continue to combine knowledge of mechanics with other relevant research techniques, and to identify mechanical markers of joint health and structural and functional disease progression that are needed to best inform disease prevention, monitoring, and treatment.

Clinical and biomechanical changes following a 4-month toe-out gait modification program for people with medial knee osteoarthritis: a randomized controlled trial.

OBJECTIVE: To compare changes in knee pain, function, and loading following a 4-month progressive walking program with or without toe-out gait modification in people with medial tibiofemoral knee osteoarthritis. DESIGN: Individuals with medial knee osteoarthritis were randomized to a 4-month program to increase walking activity with (toe-out) or without (progressive walking) concomitant toe-out gait modification. The walking program was similar between the two groups, except that the gait modification group was trained to walk with 15° more toe-out. Primary outcomes included: knee joint pain (WOMAC), foot progression angles and knee joint loading during gait (knee adduction moment (KAM)). Secondary outcomes included WOMAC function, timed stair climb, and knee flexion moments during gait. RESULTS: Seventy-nine participants (40 in toe-out group, 39 in progressive walking group) were recruited. Intention-to-treat analysis showed no between-group differences in knee pain, function, or timed stair climb. However, the toe-out group exhibited significantly greater changes in foot progression angle (mean difference = -9.04° (indicating more toe-out), 95% CI: -11.22°, -6.86°; P < 0.001), late stance KAM (mean difference = -0.26 %BW*ht, 95% CI: -0.39 %BW*ht, -0.12 %BW*ht, P < 0.001) and KAM impulse (-0.06 %BW*ht*s, 95% CI: -0.11 %BW*ht*s, -0.01 %BW*ht*s; P = 0.031) compared to the progressive walking group at follow-up. The only between-group difference that remained at a 1-month retention assessment was foot progression angle, with greater changes in the toe-out group (mean difference = -6.78°, 95% CI: -8.82°, -4.75°; P < 0.001). CONCLUSIONS: Though both groups experienced improvements in self-reported pain and function, only the toe-out group experienced biomechanical improvements. TRIALS REGISTRY NUMBER: NCT02019108.

Kinetic risk factors of running-related injuries in female recreational runners.

Our objective was to prospectively investigate the association of kinetic variables with running-related injury (RRI) risk. Seventy-four healthy female recreational runners ran on an instrumented treadmill while 3D kinetic and kinematic data were collected. Kinetic outcomes were vertical impact transient, average vertical loading rate, instantaneous vertical loading rate, active peak, vertical impulse, and peak braking force (PBF). Participants followed a 15-week half-marathon training program. Exposure time (hours of running) was calculated from start of program until onset of injury, loss to follow-up, or end of program. After converting kinetic variables from continuous to ordinal variables based on tertiles, Cox proportional hazard models with competing risks were fit for each variable independently, before analysis in a forward stepwise multivariable model. Sixty-five participants were included in the final analysis, with a 33.8% injury rate. PBF was the only kinetic variable that was a significant predictor of RRI. Runners in the highest tertile (PBF < -0.27 BW) were injured at 5.08 times the rate of those in the middle tertile and 7.98 times the rate of those in the lowest tertile. When analyzed in the multivariable model, no kinetic variables made a significant contribution to predicting injury beyond what had already been accounted for by PBF alone. Findings from this study suggest PBF is associated with a significantly higher injury hazard ratio in female recreational runners and should be considered as a target for gait retraining interventions.

Motor unit recruitment and firing rate in medial gastrocnemius muscles during external perturbations in standing in humans.

There is limited investigation of the interaction between motor unit recruitment and rate coding for modulating force during standing or responding to external perturbations. Fifty-seven motor units were recorded from the medial gastrocnemius muscle with intramuscular electrodes in response to external perturbations in standing. Anteriorly directed perturbations were generated by applying loads in 0.45-kg increments at the pelvis every 25-40 s until 2.25 kg was maintained. Motor unit firing rate was calculated for the initial recruitment load and all subsequent loads during two epochs: 1) dynamic response to perturbation directly following each load drop and 2) maintenance of steady state between perturbations. Joint kinematics and surface electromyography (EMG) from lower extremities and force platform measurements were assessed. Application of the external loads resulted in a significant forward progression of the anterior-posterior center of pressure (AP COP) that was accompanied by modest changes in joint angles (<3°). Surface EMG increased more in medial gastrocnemius than in the other recorded muscles. At initial recruitment, motor unit firing rate immediately after the load drop was significantly lower than during subsequent load drops or during the steady state at the same load. There was a modest increase in motor unit firing rate immediately after the load drop on subsequent load drops associated with regaining balance. There was no effect of maintaining balance with increased load and forward progression of the AP COP on steady-state motor unit firing rate. The medial gastrocnemius utilized primarily motor unit recruitment to achieve the increased levels of activation necessary to maintain standing in the presence of external loads.

Effects of a 10-week toe-out gait modification intervention in people with medial knee osteoarthritis: a pilot, feasibility study.

OBJECTIVE: To examine the feasibility of a 10-week gait modification program in people with medial tibiofemoral knee osteoarthritis (OA), and to assess changes in clinical and biomechanical outcomes. DESIGN: Fifteen people with medial knee OA completed 10 weeks of gait modification focusing on increasing toe-out angle during stance 10° compared to their self-selected angle measured at baseline. In addition to adherence and performance difficulty outcomes, knee joint symptoms (Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale and total score, numerical rating scale (NRS) of pain), and knee joint loading during gait (late stance peak knee adduction moment (KAM)) were assessed. RESULTS: Participants were able to perform the toe-out gait modification program with minimal to moderate difficulty, and exhibited significant increases in self-selected toe-out angle during walking (P < 0.001). Joint discomfort was reported by five participants (33%) in the hip or knee joints, though none lasted longer than 2 weeks. Participants reported statistically significant reductions in WOMAC pain (P = 0.02), NRS pain (P < 0.001), WOMAC total score (P = 0.02), and late stance KAM (P = 0.04). CONCLUSIONS: These preliminary findings suggest that toe-out gait modification is feasible in people with medial compartment knee OA. Preliminary changes in clinical and biomechanical outcomes provide the impetus for conducting larger scale studies of gait modification in people with knee OA to confirm these findings.

Lateral trunk lean gait modification increases the energy cost of treadmill walking in those with knee osteoarthritis.

OBJECTIVE: To compare the energy expenditure of increased lateral trunk lean walking - a suggested method of reducing medial compartment knee joint load - compared to normal walking in a population of older adults with medial knee osteoarthritis (OA). METHOD: Participants completed two randomly-presented treadmill walking conditions: 15 min of normal walking or walking with ten degrees of peak lateral trunk lean. Lateral trunk lean angle was displayed in front of the participant in real-time during treadmill conditions. Energy expenditure (VO2 and METs), heart rate (HR), peak lateral trunk lean angle, knee pain and perceived exertion were measured and differences between conditions were compared using paired t-tests. RESULTS: Twelve participants (five males, mean (standard deviation (SD)) age 64.1 (9.4) years, body mass index (BMI) 28.3 (4.9) kg/m²) participated. All measures were significantly elevated in the lateral trunk lean condition (P < 0.008), except for knee pain (P = 0.22). Oxygen consumption (VO2) was, on average 9.5% (95% CI 4.2-14.7%) higher, and HR was on average 5.3 beats per minute (95% CI 1.7-9.0 bpm) higher during increased lateral trunk lean walking. CONCLUSION: Increased lateral trunk lean walking on a treadmill resulted in significantly higher levels of steady-state energy expenditure, HR, and perceived exertion, but no difference in knee pain. While increased lateral trunk lean has been shown to reduce biomechanical measures of joint loading relevant to OA progression, it should be prescribed with caution given the potential increase in energy expenditure experienced when it is employed.

Altering foot progression angle in people with medial knee osteoarthritis: the effects of varying toe-in and toe-out angles are mediated by pain and malalignment.

OBJECTIVES: To evaluate if altering the foot progression angle (FPA) by varying magnitudes during gait alters the external knee adduction moment (KAM), knee flexion moment (KFM), knee extension moment (KEM) and/or symptoms in people with medial knee osteoarthritis (OA). Potential influence of pain and knee malalignment on load-modifying effects of FPA was investigated. DESIGN: Participants (n = 22) underwent 3-dimensional gait analysis to measure KAM peaks, KAM impulse, KFM and KEM peaks. Following natural gait, five altered FPA conditions were performed in random order (10° toe-in, 0° FPA, 10° toe-out, 20° toe-out and 30° toe-out). A projection screen displayed their real-time FPA. Pain/discomfort at knees and feet/ankles were evaluated for each condition. Linear mixed models were used for statistical analysis. RESULTS: Toe-in reduced the early stance peak KAM and KEM but increased the KAM impulse, late stance peak and KFM. Toe-out reduced the KAM impulse, late stance peak and KFM (P < 0.001) but increased the early stance peak KAM and KEM. All effects were greater in participants with more varus knees. Pain significantly mediated the effect of altered FPA on the KAM impulse and late stance peak. In more painful individuals, toe-in was predicted to reduce the KAM impulse and late stance peak, and increase them for toe-out gait. There were no immediate symptomatic changes. CONCLUSIONS: Effects of altered FPA vary across all medial knee load parameters and it is difficult to determine an optimal direction of FPA change. Future studies should consider Western Ontario McMaster Universities OA Index (WOMAC) pain to judge the likely effects of altered FPA.

Contralateral cane use and knee joint load in people with medial knee osteoarthritis: the effect of varying body weight support.

OBJECTIVE: To evaluate the effect of varying body weight support (BWS) with contralateral cane use on medial knee load, measured by external knee adduction moment (KAM), in medial knee osteoarthritis (OA) participants. Influences of cane use technique, pain and malalignment on the cane's load-reducing effects were investigated. METHOD: Participants (n=23) underwent three-dimensional gait analysis to measure KAM peaks (early and late stance) and impulse. Unaided walking was firstly analyzed. Following cane use training, participants placed pre-determined magnitudes of BWS through the cane (10%, 15% and 20% in random order), with visual feedback provided via a force-instrumented cane and projection screen. Contributions of cane use technique (peak BWS magnitude and timing, cane impulse (BWS∗time) anterior and lateral cane distance from limb) and Western Ontario McMaster Universities OA Index (WOMAC) pain and malalignment to KAM outcomes were evaluated using linear mixed models. RESULTS: Cane use reduced all KAM variables, with a dose-response effect apparent. Cane BWS impulse was important in reducing the early stance peak KAM (P<0.001), peak BWS for late stance KAM (P<0.001) and both BWS measures for KAM impulse reductions (P<0.001). Variables contributing to efficacy of load-reduction differed across outcomes. Generally, greater reductions were achieved with longer lateral cane distances, peak BWS timing similar to KAM peaks, and shorter anterior cane distances. Greater pain and varus alignment improved load-reduction for some outcomes. CONCLUSION: Contralateral cane use significantly reduced medial knee load, with a dose-response effect. Medial knee OA patients should be encouraged to maintain greater BWS across stance, with cane placement more lateral for optimum benefit.

Hip strengthening reduces symptoms but not knee load in people with medial knee osteoarthritis and varus malalignment: a randomised controlled trial.

OBJECTIVE: To determine whether hip abductor and adductor muscle strengthening reduces medial compartment knee load and improves symptoms in people with medial tibiofemoral OA and varus malalignment. METHODS: In a randomised controlled trial, 89 participants were randomly allocated to a hip strengthening group or to a control group with no intervention. The strengthening group performed a physiotherapist-supervised home exercise program targeting the hip abductor and adductor muscles for 12 weeks. The primary outcome was the peak external knee adduction moment measured using three-dimensional gait analysis by a blinded assessor. Secondary outcomes included a pain numeric rating scale, Western Ontario and McMaster Universities Osteoarthritis Index, step test, stair climb test, maximum isometric strength of hip and quadriceps muscles and participant-perceived rating of overall change. Intention-to-treat analyses were performed using linear regression modelling adjusting for baseline outcomes and other characteristics. RESULTS: The trial was completed by 76/89 participants (85%). There was no significant between-group difference in change in the knee adduction moment [mean difference (95% confidence interval (CI)) 0.134 (-0.069 to 0.337) Nm/BW x HT%]. All pain, physical function and muscle strength measures showed significantly greater improvement in the strengthening group (all P<0.05). The relative risk (95% CI) of participant-perceived overall improvement in the strengthening group compared to the control group was 20.02 (6.21-64.47). CONCLUSIONS: Although strengthening the hip muscles improved symptoms and function in this patient group, it did not affect medial knee load as measured by the knee adduction moment. Thus it is unlikely that hip muscle strengthening influences structural disease progression. TRIAL REGISTRATION: ACTR12607000001493.

Physiological arousal accompanying postural responses to external perturbations after stroke.

OBJECTIVE: The purpose of this study was to examine simultaneously the level of physiological arousal and the postural response to external perturbations in people post-stroke compared to age-matched controls to build a more comprehensive understanding of the effect of stroke on postural control and balance self-efficacy. METHODS: Participants stood with each foot on separate force platforms. Ten applications of loads of 2% body weight at the hips perturbed the participant anteriorly under two conditions: investigator-triggered or self-triggered (total 20). Electrodermal activity (EDA; measurement of physiological arousal), electromyography (EMG) of the ankle plantarflexor muscles and anterior-posterior center of pressure measurements were taken pre-perturbation (anticipatory) and post-perturbation (response) and compared between the initial (first two) and final (last two) perturbations. RESULTS: Participants post-stroke demonstrated significantly higher levels of anticipatory EDA and anticipatory paretic plantarflexor EMG during both self- and investigator-triggered conditions compared to controls. Anticipatory EDA levels were higher in the final perturbations in participants post-stroke in both conditions, but not in controls. Habituation of the EDA responses post-perturbation was exhibited in the self-triggered perturbations in controls, but not in participants post-stroke. CONCLUSIONS: Physiological arousal and postural control strategies of controls revealed habituation in response to self-triggered perturbations, whereas this was not seen in participants post-stroke. SIGNIFICANCE: Understanding the physiological arousal response to challenges to standing balance post-stroke furthers our understanding of postural control mechanisms post-stroke.

Localized prostate cancer treated by external-beam radiotherapy alone: serum prostate-specific antigen--driven outcome analysis.

PURPOSE: To determine the 5-year rate of survival with no evidence of disease (NED) using strict biochemical criteria in men with prostate cancer treated by external-beam radiotherapy alone and to examine possible clinical and treatment factors that predict the likelihood of NED survival. MATERIALS AND METHODS: Five hundred men with clinically localized prostate cancer consecutively treated with external-beam radiotherapy alone with no prior, concomitant, or adjuvant endocrine therapy were identified. All patients had serial serum prostate-specific antigen (PSA) values determined after treatment and 451 patients had pretreatment PSA values determined. The median follow-up duration is 20 months (range, 2 to 72; mean, 36). RESULTS: The 5-year rate of overall survival in this group of patients was 80%. The 5-year rate of survival without clinical evidence of disease (cNED) was 72%. The 5-year rate of survival without evidence of clinical, radiographic, or biochemical relapse (bNED) was 51%. Multivariate analysis demonstrated that a pretreatment serum PSA level < or = 15 ng/mL was the most important predictor of bNED survival (P < .0001). Patients with early-stage (T1, T2a/b) tumors and a pretreatment serum PSA less than 15 ng/mL had a 3-year rate of bNED survival of 86%. The rate of bNED survival for patients with a pretreatment PSA level greater than 15 ng/mL was 38% at 3 years. CONCLUSION: Pretreatment serum PSA level is the most important predictor of treatment outcome in this group of patients treated with definitive radiotherapy alone. External-beam radiation alone can produce acceptable early rates of bNED survival in patients with clinically organ-confined tumors and a pretreatment PSA level < or = 15 ng/mL. To produce acceptable results in those patients with pretreatment PSA levels more than 15 ng/mL, effective adjuvant treatments in addition to aggressive local treatments are necessary.

Behavior of medial gastrocnemius motor units during postural reactions to external perturbations after stroke.

OBJECTIVE: This study investigated the behavior of medial gastrocnemius (GM) motor units (MU) during external perturbations in standing in people with chronic stroke. METHODS: GM MUs were recorded in standing while anteriorly-directed perturbations were introduced by applying loads of 1% body mass (BM) at the pelvis every 25-40s until 5% BM was maintained. Joint kinematics, surface electromyography (EMG), and force platform measurements were assessed. RESULTS: Although external loads caused a forward progression of the anterior-posterior centre of pressure (APCOP), people with stroke decreased APCOP velocity and centre of mass (COM) velocity immediately following the highest perturbations, thereby limiting movement velocity in response to perturbations. MU firing rate did not increase with loading but the GM EMG magnitude increased, reflecting MU recruitment. MU inter spike interval (ISI) during the dynamic response was negatively correlated with COM velocity and hip angular velocity. CONCLUSIONS: The GM utilized primarily MU recruitment to maintain standing during external perturbations. The lack of MU firing rate modulation occurred with a change in postural central set. However, the relationship of MU firing rate with kinematic variables suggests underlying long-loop responses may be somewhat intact after stroke. SIGNIFICANCE: People with stroke demonstrate alterations in postural control strategies which may explain MU behavior with external perturbations.

Factors influencing incidence of acute grade 2 morbidity in conformal and standard radiation treatment of prostate cancer.

PURPOSE: The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of acute grade 2 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. METHODS AND MATERIALS: Two hundred and forty-seven consecutive patients treated with conformal technique are combined with and compared to 162 consecutive patients treated with standard techniques. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using the retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Univariate analysis compares differences in the incidence of RTOG-EORTC grade two acute morbidity by technique, T stage, age, irradiated volume, and dose. Multivariate logistic regression includes these same variables. RESULTS: In nearly all categories, the conformal treatment group experienced significantly fewer acute grade 2 complications than the standard treatment group. Only volume (prostate +/- whole pelvis) and technique (conformal vs. standard) were significantly related to incidence of morbidity on multivariate analysis. When dose is treated as a continuous variable (rather than being dichotomized into two levels), a trend is observed on multivariate analysis, but it does not reach significant levels. The incidence of acute grade 2 morbidity in patients 65 years or older is significantly reduced by use of the conformal technique. CONCLUSION: The conformal technique is associated with fewer grade 2 acute toxicities for all patients. This conclusion is valid irrespective of selection criteria except in a few cases. Older age is associated with increased toxicity only with the standard technique and not then at a statistically significant level. Elderly patients should not be excluded from external beam radiation because of increased morbidity especially if conformal treatment is available. Volume is not significantly related to morbidity in patients with standard treatment, but it is for conformal treatment. Furthermore, it remains significant in a multivariate analysis that also shows the advantage of conformal treatment. Grade 2 acute toxicities are more volume dependent than dose dependent.

Matchline dosimetry of a three field technique for breast treatment using cobalt or 6 MV X rays.

The matchline dose distribution between the tangential and supraclavicular fields used for treatment of breast cancer was investigated using 60Co and 6 MV X rays. Techniques which allow minimum, moderate, and maximum overlap between the fields as well as a geometric alignment technique were studied. For a given technique, comparable matchline widths and doses were obtained with either machine. Average matchline doses were slightly greater with 6 MV X rays, however, more tissue was irradiated to higher dose levels with 60Co. Among the techniques which do not geometrically align the three fields, doses as high as 150% or as low as 70% were observed depending on the amount of overlap between the fields. Matching the tangents 3.5 cm medial and lateral to the supraclavicular field center yielded average maximum and minimum matchline doses within ten percent of those with geometric alignment techniques. However, these distributions will vary with patient size and matchline length. Geometric alignment techniques offer the advantages of matchline dose uniformity and reproducibility over the patient population with maximum matchline doses of only 110-115%.

Effect of low-density lateral interfaces on soft-tissue doses.

PURPOSE: Doses at the interface between tissue and low-density inhomogeneities with the interface positioned perpendicular to the beam direction have been well studied. When the inhomogeneity lies parallel to the beam direction (i.e., a lateral interface), the resulting dose distribution is not as well known. Lateral lung-soft-tissue interfaces are common in many fields used to treat malignancies in the thorax region including tangential breast fields and anteroposterior fields for lung and esophageal cancer. The purpose of this study was to evaluate the dose distribution along lateral interfaces and to determine the implications for treatment. METHODS AND MATERIALS: A polystyrene and cork slab phantom was irradiated from the side to simulate treatment fields with lateral lung-soft-tissue interfaces. The beam was positioned with the isocenter in polystyrene and the field edge in cork. Cork slabs (0.6-2.5 cm) were used to simulate different thicknesses of lung between the field edge and the target volume. Measurements were made using a parallel plate ionization chamber. With the chamber position held constant, polystyrene slabs were added between the cork and the chamber to study the dose distribution in the interface region. Interface doses were studied as a function of the amount of cork in the field, field size, beam energy (6-18 MV), and depth. RESULTS: Doses in the interface region were lower by as much as 10% compared to doses in a homogeneous phantom. For a given cork width and field size, the magnitude of the underdose increased by several percent as the x-ray energy increased from 6 to 18 MV. The underdose at the interface was 5% for 6 MV and 8% for 18 MV X-rays with a 1-cm cork width. For a 2.5-cm cork width, underdoses of 2.5% and 3% at distances up to 2.5 and 4 mm lateral to the interface were observed for 6- and 18-MV X-rays, respectively. However, doses right at the interface were 1% greater for 6 MV and 3% less for 18 MV than doses in a homogeneous phantom. For a given cork width, the interface doses were not significantly dependent on field width but decreased by an additional 2-3% as the length decreased to 4 cm. Additional decreases were also observed when the measurement depth decreased to 3 cm. With a 1-cm width of cork in the field, a lateral distance of 3-4 mm from the interface was necessary to ensure doses of at least 98% of the homogenous dose with 6-MV X-rays. A lateral distance of 6-7 mm was necessary for 10- and 18-MV X-rays. CONCLUSION: Underdosing will occur in the soft tissues adjacent to low-density inhomogeneities. The magnitude depends primarily on the width of the inhomogeneity seen in the treatment field, but also on field size, depth, and beam energy. For treatment fields with a lateral lung interface, a segment of tissue approximately 3-4 mm thick for 6 MV and 6-7 mm thick for higher-energy beams may be underdosed. Lung widths of > or = 1.75 cm as observed on film will generally guarantee doses of at least 96% of those calculated with no inhomogeneity corrections. High-energy beams are often used to treat sites in the thorax or breast to improve dose homogeneity throughout the treatment volume. Potential underdosing due to the presence of lung should be considered and may require a decrease in beam energy or an increase in the margin between the target volume and the field edge to ensure adequate treatment.

An evaluation of setup uncertainties for patients treated to pelvic sites.

PURPOSE: Successful delivery of conformal fields requires stringent immobilization and treatment verification, as well as knowledge of the setup reproducibility. The purpose of this study was to compare the three-dimensional distribution of setup variations for patients treated to pelvic sites with electronic portal imaging devices (EPID) and portal film. METHODS AND MATERIALS: Nine patients with genitourinary and gynecological cancers immobilized with custom casts and treated with a four-field whole-pelvis technique were imaged daily using an EPID and filmed once every five to seven treatments. The three-dimensional translational and rotational setup errors were determined using a technique that relies on anatomical landmarks identified on simulation and treatment images. The distributions of the translational and rotational variations in each dimension as well as the total displacement of the treatment isocenter from the simulation isocenter were determined. RESULTS: Grouped analysis of all patients revealed average unidirectional translational deviations of less than 2 mm and a standard deviation of 5.3 mm. The average total undirected distance between the treatment and simulated isocenters was 8.3 mm with a standard deviation of 5 mm. Individual patient analysis revealed eight of nine patients had statistically significant nonzero mean translational variations (p < 0.05). Translational variations measured with film were an average of 1.4 mm less than those measured with EPID, but this difference was not statistically significant. CONCLUSION: Translational variations measured in this study are in general agreement with previous studies. The use of the EPID in this study was less intrusive and may have resulted in less additional attention being given each imaging setup. This may explain the slightly larger average translational variations observed with EPID vs. film, and suggests that the use of EPIDs is a superior method for assessing the true extent of setup displacements. Although no statistically significant translational variations for the patient group overall were observed, 90% of patients had significant translational variations in at least one direction when analyzed separately. The margin to be added to the clinical target volume (CTV) to account for setup uncertainties will depend on whether it is possible to identify patients with significant translational variations, and to eliminate these displacements from routine treatments. The choice to eliminate these variations and to use a smaller CTV margin will have to be accompanied by stringent frequent position verification methods and repositioning.

The effect of setup uncertainties on the treatment of nasopharynx cancer.

PURPOSE: As radiation treatment techniques become more complicated, the need to understand the effect of uncertainties on dose distributions increases. This study investigates the effect of positional uncertainities for patients with nasopharynx carcinoma treated with a multiple field conformal boost technique. Three dimensional setup errors were measured for six patients and the effect on patient dose was evaluated using dose volume histograms. METHODS AND MATERIALS: A method is presented for determining 3-dimensional translational and rotational setup errors by identifying anatomical landmarks on two treatment field images and their corresponding simulation images. Measurements were made on a daily basis for six patients undergoing conformal treatment. RESULTS: The average magnitude of the translational errors was between 1.5 and 3 mm while the average distance between simulation and treatment isocenters was 5 mm. Both systematic and random setup errors were observed. Dose volume histograms incorporating these uncertainties for standard parallel opposed and conformal techniques were generated for patients experiencing random and systematic setup errors. CONCLUSION: The data imply that positional uncertainties effect the daily dose distributions for target and critical structures differently and that the effect may be treatment technique dependent. These results demonstrate the need to measure setup uncertainties for all sites and to develop techniques for incorporating dose uncertainties in treatment plans.

Incidence of and factors related to late complications in conformal and conventional radiation treatment of cancer of the prostate.

PURPOSE: The fundament hypothesis of conformal radiation therapy is that tumor control can be increased by using conformal treatment techniques that allow a higher tumor dose while maintaining an acceptable level of complications. To test this hypothesis, it is necessary first to estimate the incidence of morbidity for both standard and conformal fields. In this study, we examine factors that influence the incidence of late Grade 3 and 4 morbidity in patients treated with conformal and standard radiation treatment for prostate cancer. METHODS AND MATERIALS: Six hundred sixteen consecutive patients treated with conformal or standard techniques between 1986 and 1994 to doses greater than 65 Gy and with more than 3 months follow-up were analyzed. No patients treated with prostatectomies were included in the analysis. The conformal technique includes special immobilization by a cast, careful identification of the target volume in three dimensions, localization of the inferior border of the prostate using a retrograde urethrogram, and individually shaped portals that conform to the Planning Target Volume (PTV). Multivariate analysis using a proportional hazards model compares differences in the incidence of Radiation Therapy Oncology Group/European Organization for Research and Center Treatment (RTOG/EORTC) Grade 3 and 4 late gastrointestinal (GI) and genitourinary (GU) morbidity by technique, T-stage, grade, age, hormonal treatment, irradiated volume, dose, and comorbid conditions. Grade 3 rectal bleeding was defined as requiring three or more cautery procedures. RESULTS: The overall actuarial incidence of genitourinary (GU) toxicities at 5 years was 3.4%, with the crude incidence being six cases in 616 patients satisfying the selection criteria; for gastrointestinal (GI) toxicities, the overall actuarial incidence was 2.7%, with the crude incidence being 13 cases out of 616 patients. The average time to complication for our patients was 12.8 months for GI toxicity and 32.9 months for GU toxicity (p < 0.001). No factors were found that were predictive for GU morbidity. The only factors significantly related to incidence of late GI morbidity on multivariate analysis of our data were dose and age. The central axis dose was a more significant variable than the dose prescribed to the Treated Volume. Age was negatively correlated with late GI morbidity, with older patients having a reduced incidence of toxicity. The median tolerance dose for GI complications was estimated to be 92.8 Gy, and the dose for 10% incidence was estimated to be 80.2 Gy. Treating the pelvis to 45 Gy did not increase the incidence of late morbidity. Late GI and GU toxicities were not correlated. CONCLUSION: The conformal technique has been associated with fewer acute Grade 2 toxicities (6). The use of conformal fields did not decrease the incidence of late GI morbidity; however, patients with this technique invariably had higher doses. Because of the dose response for this complication and the correlation between the dose and the use of conformal fields, one would not expect to demonstrate an advantage to conformal fields in this data set. On the other hand, no dose effect was observed for late GU morbidity. In this case, there appears to be an advantage for conformal treatment that has not reached statistical significance because the follow-up time is shorter than for the patients treated with conventional fields and the latency for GU morbidity is long.

Conformal static field radiation therapy treatment of early prostate cancer versus non-conformal techniques: a reduction in acute morbidity.

Patients with early prostate cancer have been definitively treated using our previously described technique of CT-based 3D treatment planning and beam's eye view techniques with patients immobilized in alpha cradle casts. An average of 14% bladder (range 6-31%) and 14% rectal (range 7-25%) volume receiving a given dose was eliminated using four conformally blocked fields, with a 1.5 cm margin around the prostate contour, when compared to stage matched controls. Treatment-related acute morbidity was compared for 26 patients treated by the conformal techniques (CG) since April 1989 and 20 consecutive patients treated immediately prior to the conformal techniques with prostate only fields from May 1985-March 1989 (NCG). Acute urinary symptoms (frequency, dysuria, hematuria) or acute rectal symptoms (diarrhea, tenesmus, blood) occurred in 77% (20/26) of the CG versus 80% (16/20) of the NCG patients. Only 31% (8/26) of the CG versus 60% (12/20) of the NCG patients (p < .05) experienced symptoms to a degree which prompted physician intervention (medication and/or interruption of treatment). Two of 26 CG patients (8%) required medication for both bladder and rectal symptoms compared to 5/20 (25%) NCG patients (p = .09). Symptoms persisted for an average of 2.5 weeks versus 3.5 weeks in the CG and NCG groups, respectively. Persistent symptoms at or beyond the 1 month follow-up were present in 3/26 (11%) CG patients (average duration 1.5 months) and were present in 4/20 (20%) of the NCG patients (average duration 2.5 months). Thus, although the percentage of patients who experience acute irritation of the bladder and/or rectum is similar in the two groups, it appears that the percentage requiring medication and/or interruption of treatment is significantly less when 3D treatment planning, rigid immobilization, and conformal blocks are used. The amount of bladder and rectal tissue that is eliminated by our conformal technique is important as shown clinically by the lesser severity and shorter duration of acute symptomatology.