Revolutionizing cancer treatment in India: Evaluating the unmet need, economics, and a roadmap for project implementation of particle therapy.

INTRODUCTION: This study aims to quantitatively assess eligible patients and project the demand for particle therapy facilities in India from 2020 to 2040. In addition, an economic analysis evaluates the financial feasibility of implementing this technology. The study also examines the prospective benefits and challenges of adopting this technology in India. METHODOLOGY: Cancer incidence and projected trends were analyzed for pediatric patients using the Global Childhood Cancer microsimulation model and adult patients using the Globocan data. Economic cost evaluation is performed for large-scale combined particle (carbon and proton-three room fixed-beam), large-scale proton (one gantry and two fixed-beam), and small-scale proton (one gantry) facility. RESULTS: By 2040, the estimated number of eligible patients for particle therapy is projected to reach 161,000, including approximately 14,000 pediatric cases. The demand for particle therapy facilities is projected to rise from 81 to 97 in 2020 to 121 to 146 by 2040. The capital expenditure is estimated to be only 3.7 times that of a standard photon linear accelerator over a 30-year period. Notably, the treatment cost can be reduced to USD 400 to 800 per fraction, substantially lower than that in high-income countries (USD 1000 to 3000 per fraction). CONCLUSION: This study indicates that, in the Indian scenario, all particle therapy models are cost-beneficial and feasible, with large-scale proton therapy being the most suitable. Despite challenges such as limited resources, space, a skilled workforce, referral systems, and patient affordability, it offers substantial benefits. These include the potential to treat many patients and convenient construction and operational costs. An iterative phased implementation strategy can effectively overcome these challenges, paving the way for the successful adoption of particle therapy in India. PLAIN LANGUAGE SUMMARY: In India, eligible patients benefiting from high-precision particle therapy technology projected to rise till 2040. Despite high upfront costs, our study finds the long-term feasibility of all particle therapy models, potentially offering a substantial reduction in treatment cost compared to high-income countries. Despite challenges, India can succeed with an iterative phased approach.

Dosimetric impact of dwell time deviation constraint on inverse brachytherapy treatment planning and comparison with conventional optimization method for interstitial brachytherapy implants.

PURPOSE: High-dose rate remote afterloading brachytherapy machine and advanced treatment planning system help in getting optimum dose to tumor and low dose to normal structures. Inverse planning simulated annealing (IPSA) optimization technique has a unique feature of dwell time deviation constraint (DTDC). In this study, six IPSA-based plans having different DTDC values with routinely practiced geometric plus graphical optimization (GO + GrO) have been compared using various dosimetric parameters. MATERIALS AND METHODS: For this retrospective study, we have generated IPSA-optimized interstitial brachytherapy plans for ten cancer cervix patients. Routinely practiced GO + GrO-based plans were compared with six different IPSA plans having varying DTDC values from 0.0 to 1.0 using different dosimetric indices. RESULTS: Conformity index and homogeneity index (HI) were higher in GO + GrO plans, compared to IPSA-optimized plans. However, HI of IPSA plans was increasing with increasing DTDC values. High-dose volumes were well controllable using DTDC parameter in IPSA-optimized plans. Dose to the rectum and bladder was smaller for IPSA-optimized plans than GO + GrO plans. CONCLUSIONS: One of the benefits of applying DTDC in IPSA-optimized plan is that it reduces high-dose volumes. Another advantage is the reduction in rectum and bladder dose.

Study of the effects of dwell time deviation constraints on inverse planning simulated annealing optimized plans of intracavitary brachytherapy of cancer cervix.

PURPOSE: High Dose Rate (HDR) remote afterloading brachytherapy machine and advanced treatment planning system have made it possible to make variations in individual dwell times across a catheter according to tumour density and for sparing normal structures. New inverse planning technique such as Inverse Planning Simulated Annealing (IPSA) has also been introduced. But very few institutions are venturing towards volume based IPSA optimised intracavitary brachytherapy. This study focuses on dwell time deviation constraint (DTDC) feature of IPSA based optimization which restricts the large variation of dwell time across the catheter. METHODS AND MATERIAL: For this retrospective study we have generated IPSA optimised intracavitary brachytherapy plans for 20 cancer cervix applications. The initial DTDC value of each IPSA plan was kept 0.0. Later on gradual increment was made in DTDC values in step of 0.2. Plan modulation index (M) defined by Ryan L. Smith et al was used for characterising the variation of dwell time modulation with respect to gradual increase in DTDC parameter. RESULTS: Plan modulation index gradually decreases with increasing value of DTDC from 0.0 to 1.0. There was the 83% decrease in M value from IPSA of DTDC 0.0 to fully constrained IPSA of DTDC1.0. There is reduction of 8.26% and 6.95% for D2cc values of rectum and bladder respectively for DTDC 1.0 compared to DTDC 0.0. CONCLUSIONS: One of the benefits of applying DTDC constrained in IPSA plan is that, it removes local hot spots. It's another advantage is the reduction in rectum and bladder dose.

Indigenously developed multipurpose acrylic head phantom for verification of IMRT using film and gel dosimetry.

The purpose of this study was to validate the newly designed acrylic phantom for routine dosimetric purpose in radiotherapy. The phantom can be used to evaluate and compare the calculated dose and measured dose using film and gel dosimetric methods. In this study, a doughnut-shaped planning target volume (8.54 cm3) and inner organ at risk (0.353 cm3) were delineated for an IMRT test plan using the X-ray CT image of the phantom. The phantom consists of acrylic slabs which are integrated to form a human head with a hole in the middle where several dosimetric inserts can be positioned for measurement. An inverse planning with nine coplanar intensity-modulated fields was created using Pinnacle TPS. For the film analysis, EBT2 film, flatbed scanner, in-house developed MATLAB codes and ImageJ software were used. The 3D dose distribution recorded in the MAGAT gel dosimeter was read using a 1.5 T MRI scanner. Scanning parameters were CPMG pulse sequence with 8 equidistant echoes, TR = 5600, echo step = 22 ms, pixel size = 0.5 × 0.5, slice thickness = 2 mm. Using a calibration relationship between absorbed dose and spin-spin relaxation rate (R2), R2 images were converted to dose images. The dose comparison was accomplished using in-house MATLAB-based graphical user interface named "IMRT3DCMP". For gel measurement dose grid from the TPS was extracted and compared with the measured dose grid of the gel. Gamma index analysis of film measurement for the tolerance criteria of 2%/2mm, 1%/1 mm showed more than 90% voxels pass rate. Gamma index analysis of 3D gel measurement data showed more than 90% voxels pass rate for different tolerance criteria of 2%/2 mm and 1%/1 mm. Overall both 2D and 3D measurement were in close agreement with the Pinnacle TPS calculated dose. The phantom designed is cost-effective and the results are promising, but further investigation is required to validate the phantom with other 3D conformal techniques for dosimetric purpose.

Telomeric DNA quantity, DNA damage, and heat shock protein gene expression as physiological stress markers in chickens.

In this longitudinal study with Single Comb White Leghorn chickens, we investigated the effects of stress conditions in birds that were subjected to a high stocking density with feed restrictions on the quantity of telomeric DNA, the rate of DNA damage, and the expression levels of heat shock proteins (HSP) and hydroxyl-3-methyl-glutaryl coenzyme A reductase (HMGCR) genes. The telomere length and telomere-shortening rates were analyzed by quantitative fluorescence in situ hybridization on the nuclei of lymphocytes. The DNA damage rate of lymphocytes was quantified by the comet assay. The expression levels of HSP70, HSP90, and HMGCR genes were measured by quantitative real-time PCR in lymphocytes. The telomere-shortening rate of the lymphocytes was significantly higher in the stress group than in the control. The DNA damage also increased in birds raised under stress conditions, as compared with the control group. The stress conditions had a significant effect on the expressions of HMGCR and HSP90α in lymphocytes but had no significance on HSP70 and HSP90ß in blood. We conclude that the telomere length, especially the telomere-shortening rates, the quantification of total DNA damage, and the expression levels of the HMGCR and HSP90α genes can be used as sensitive physiological stress markers in chickens.

SU-E-T-597: Influence of Smoothing Parameters on Dynamic IMRT Plan Quality and Deliverability.

PURPOSE: To study the impact of different smoothing parameters on IMRT plan quality and deliverabilityMethods: Five previously treated patients of carcinoma cervix were chosen. Planning target volume (PTV) and organ at risk (OAR) i.e. bladder and rectum were contoured. In each case, five different dynamic IMRT plans with 6MV photon beam were created in eclipse TPS for Varian 2300C/D linear accelerator. During optimization, dose volume constraints and priorities were kept constant and smoothing parameters were varied as follows: 10/5, 40/30 (TPS default value), 80/60, 100/80 and 200/150 in x/y direction. Total dose was 5040cGy in 28 fractions and prescribed at 95% isodose. Plan quality was analyzed by means of coverage index (CI=PTV covered by prescription dose/PTV), OAR mean doses and total monitor units (MUs) required to deliver a plan. In each case, deliverability of treatment plans were verified with I'matriXX ion-chamber array and compared with TPS dose-plane using gamma index of 3% dose difference and 3mm distance to agreement criteria. RESULTS: The CI values were 0.9435±0.032, 0.9418±0.034, 0.9380±0.041, 0.9330±0.047 and 0.8681±0.072 for 10/5, 40/30, 80/60, 100/80 and 200/150 in x/y direction. PTV dose maximum decreases with the increase of smoothing parameters and values were 5724.38±106.08 5723.30±131.60, 5708.44±1 16.74, 5697.92±116.82 and 5587.50±189.50cGy. The bladder mean doses were 4027.46±630.40, 3821.62±420.62, 3819.58±427.08, 3813.42±435.02 and 3814.78±438.0cGy. Rectum mean doses were 3839.88±466.02, 3835.52±473.18, 3837.52±472.88, 3839.10±471.20 and 3918.94±469.76cGy. Similarly, Total MUs were 1588±205, 1573±214, 1513±274, 1456±335 and 1219±68. Gamma pass rate increases with the increase of smoothing parameters and values were 99.16±0.21%, 99.07±0.19%, 99.24±0.28%, 99.29±0.29% and 99.75±0.15%. CONCLUSIONS: When smoothing parameters decreased below TPS default value, plan quality increases, but deliverability decreases. If smoothing parameters increased above TPS default value, deliverability increases but plan quality decreases. Total MU decreases with the increase of smoothing parameters. Therefore, it's a trade-off between plan quality and deliverability which needs to be justified clinically.

SU-E-T-587: Whole IMRT, Hybrid IMRT and 3D Conformal Plan a Dosimetric Comparison for Large Target.

PURPOSE: To dosimetrically compare the whole-IMRT, hybrid-IMRT (combination of IMRT and 3D-CRT) and 3D-conformal radiotherapy (3D- CRT) plans for larger targets. METHODS: Five previously treated patients of carcinoma cervix with para-aortic lymph-nodes (target length 33-34cm) were selected. PTV-P (PTV-Primary), PTV-PA (PTV-para-aortic) and organ at risks (OARs) were defined. Three plans were generated using Eclipse TPS for Varian CL2300C/D linear accelerator using 6MV photon beam. Three plans were: (i) Whole-IMRT: IMRT for both PTV-P and PTV-PA (ii) Hybrid-IMRT: IMRT for PTV-P and 3D-CRT for PTV-PA (iii) 3D-CRT: 3D-CRT for both PTV-P and PTV-PA. Prescription dose for PTV-P is 50.4Gy and PTV-PA is 45Gy in 28 fractions. Coverage index (CI=Target volume covered by prescription dose/Target volume), mean doses to bladder, rectum and bowel were used for plan comparison by using DVH. Integral dose (liter-Gray) to normal tissue (i.e., patient volume minus PTV-P and PTV-PA) and total monitor units (MUs) required to deliver a plan was also noted. RESULTS: The CI for PTV-P is 0.98±0.20, 0.96±0.09, and 0.95±0.01 for Whole-IMRT, Hybrid-IMRT and 3D-CRT plan and for PTV- PA is 0.98±0.01, 0.98±0.01, and 0.97±0.20. Maximum doses to PTV-P are 5660.85±90.85cGy, 5640.35±70.35cGy and 5813.80±97.40cGy. Maximum doses to PTV-PA are 5000.60±109.10cGy, 5079.85±20.25cGy and 5092.25±19.75cGy. Mean doses to the bladder are 3810±225.80cGy, 3842.10±182.70cGy and 5204±98.25cGy for Whole-IMRT, Hybrid-IMRT and 3D-CRT plan, respectively. Mean doses to rectum are 3955.35±324.95cGy, 3971.15±354.15cGy and 4741.20±371.60cGy. Mean doses to bowel are 2623.35±320.85cGy, 2855.30±371.05cGy and 3011.7±433.80cGy. Average MUs required to deliver one fraction is 1285±87, 1585±186, 485±46 for Whole-IMRT, Hybrid-IMRT and 3D-CRT plans, respectively. Higher integral doses to normal tissue were observed for whole-IMRT (267.60±76 liter-Gy) followed by hybrid-IMRT (259.20±53 liter-Gy) and 3D-CRT (186.30±33 liter-Gy). CONCLUSIONS: Whole-IMRT is useful for larger targets compared to hybrid-IMRT in terms of dose conformity, lesser MUs and reduced critical organ doses with little compromise on integral dose, where 3D-CRT sacrificed the OAR sparing.

SU-E-T-268: Evaluation of Photoneutron Contamination in Elekta Synergy-S High-Energy Linear Accelerator and Indigenous Novel Solution: The AIIMS Experience.

PURPOSE: The photoneutron contamination problem was encountered due to laminated barrier wall and short maze. The purpose of this study was to report our experience in evaluating the photoneutron contamination during radiation safety survey and solution. METHODS: The photoneutron contamination measurement was carried out in Elekta Synergy-S high-energylinear accelerator for 15MV beam. A NE Neutron survey meter and for photon, Victoreen and RADOS survey meters were used. The laminated barrier wall composed of 37cm steel with 30cm concrete both side and short maze length of 5 meter. During safety survey, higher photoneutron levels for 15MV X-rays at treatment room door found. The effect of photoneutron contamination as function of neutron shielding materials of wood, polyethylene and boron and thickness, distance, locations and directions to the control console at distance upto 7 meter were investigated for 4 gantry angles at locations of treatment room entry doors namely door1(A), door2(B), console(C), conduit (D) and above-ceiling(G) for 15MV. RESULTS: The initial safety survey showed that neutron level of 47mR/h and photon leakage of 3.2mR/hr at the treatment entry room door1. The neutron values could bring down to the level of acceptance at the treatment entry door2, but the photon values are not acceptable. Therefore, 30cm concrete wall block was made at the location of door2 and another bend was taken. Finally, treatment entrance room door was made using 3cm polyethylene neutron shielding materials in order to achieve the both neutron contamination and photon leakage within the acceptable levels. CONCLUSIONS: The neutron sliding-door is operated manually in finger-push by technologist for day-to-day usage. This simple solution is cost effective and increases the patient throughput. This study underlines that one needs to take appropriate safety measures prior to facility design whenever the space constraints situations arises for high energy linear accelerator.

Interstitial brachytherapy guided intensity modulated radiation therapy (IBGIMRT) in cervical cancer: a dosimetric study.

PURPOSE: Interstitial brachytherapy (IBT) is used as an alternative to intracavitary radiotherapy in the management of cervical carcinoma. We have devised a new technique called interstitial brachytherapy guided intensity modulated radiotherapy (IBGIMRT) which can potentially reduce doses to organs at risk (OaRs). It utilizes IMRT planning on the target volume (TV) defined by implantation of IBT needles. This study compares the dosimetry of IBT and IBGIMRT. MATERIAL AND METHODS: CT scan images of 18 patients with cervical cancer, who have been already treated by HDR-BT, were used to generate two rival plans, IBT and IBGIMRT, for a prescription dose of 10 Gy. Following dosimetric factors were used for comparison: volume receiving 95% of prescription dose (V95), conformity index (COIN) and external volume index (EI) for target and for OaR, dose received by volume of 1 cm3 (D1cc), 2 cm3 (D2cc), 5 cm3 (D5cc) and also volume receiving 50% and 75% of prescription dose (V50 and V75). RESULTS: The two plans resulted in COIN difference of 49.8% (p < 0.0001) and EI difference of 36.4% (p < 0.0028) in favor of IBGIMRT. Mean D1cc, D2cc and D5cc values for bladder were 8.3 Gy, 7.6 Gy and 6.4 Gy; and 7.8 Gy, 7.3 Gy and 5.8 Gy with IBT and IBGIMRT, respectively (p > 0.05). Similar figures for rectum with IBT vs. IBGIMRT were 11.2 Gy vs. 7.02 Gy, 10.5 Gy vs. 6.4 Gy and 9.1 Gy vs. 4.8 Gy respectively (p < 0.01). CONCLUSIONS: Our novel technique, IBGIMRT, has shown its dosimetric superiority and therefore needs to be studied in clinical set up.

Normal tissue complication probability: does simultaneous integrated boost intensity-modulated radiotherapy score over other techniques in treatment of prostate adenocarcinoma.

AIM: The main objective of this study was to analyze the radiobiological effect of different treatment strategies on high-risk prostate adenocarcinoma. MATERIALS AND METHODS: Ten cases of high-risk prostate adenocarcinoma were selected for this dosimetric study. Four different treatment strategies used for treating prostate cancer were compared. Conventional four-field box technique covering prostate and nodal volumes followed by three-field conformal boost (3D + 3DCRT), four-field box technique followed by intensity-modulated radiotherapy (IMRT) boost (3D + IMRT), IMRT followed by IMRT boost (IMRT + IMRT), and simultaneous integrated boost IMRT (SIBIMRT) were compared in terms of tumor control probability (TCP) and normal tissue complication probability (NTCP). The dose prescription except for SIBIMRT was 45 Gy in 25 fractions for the prostate and nodal volumes in the initial phase and 27 Gy in 15 fractions for the prostate in the boost phase. For SIBIMRT, equivalent doses were calculated using biologically equivalent dose assuming the alpha/beta ratio of 1.5 Gy with a dose prescription of 60.75 Gy for the gross tumor volume (GTV) and 45 Gy for the clinical target volume in 25 fractions. IMRT plans were made with 15-MV equispaced seven coplanar fields. NTCP was calculated using the Lyman-Kutcher-Burman (LKB) model. RESULTS: An NTCP of 10.7 +/- 0.99%, 8.36 +/- 0.66%, 6.72 +/- 0.85%, and 1.45 +/- 0.11% for the bladder and 14.9 +/- 0.99%, 14.04 +/- 0.66%, 11.38 +/- 0.85%, 5.12 +/- 0.11% for the rectum was seen with 3D + 3DCRT, 3D + IMRT, IMRT + IMRT, and SIBIMRT respectively. CONCLUSIONS: SIBIMRT had the least NTCP over all other strategies with a reduced treatment time (3 weeks less). It should be the technique of choice for dose escalation in prostate carcinoma.

A simple technique for cranio-spinal irradiation in pediatric patients.

PURPOSE: Field matching poses challenges in craniospinal irradiation (CSI) as it leads either to underdosage or overdosage in the junctional area. A simple technique for CSI in pediatric patients is proposed. MATERIALS AND METHODS: Computed tomography scans were performed in the prone position. Two lateral cranial fields and a direct posterior spinal field were planned with a common central axis. Half-beam-blocked cranial fields with zero collimator rotation were used for treating the cranium. A half-beam-blocked field defined with jaws was used to treat the spinal column at an extended source-to-surface distance. Before treating the patient, matching of the cranial and spinal field junction along the central axis was verified with an extended dose range film. RESULTS AND CONCLUSION: The technique described is simple and easy to implement and can be applied to pediatric patients undergoing CSI. This method has the potential to reduce daily setup time and setup errors. This technique is ideally suitable for patients with spinal fields less than 30 cm.

Static versus dynamic intensity-modulated radiotherapy: Profile of integral dose in carcinoma of the nasopharynx.

This study is aimed to evaluate the impact of static and dynamic intensity modulated radiotherapy (IMRT) delivery techniques planned with Eclipse TPS on the integral dose to the healthy normal tissue surrounding the tumor-bearing area and to the volume receiving doses < 5 Gy in patients with carcinoma nasopharynx treated with Simultaneous Integrated Boost IMRT (SIB-IMRT). Ten patients with carcinoma nasopharynx were chosen for this dosimetric study. IMRT plans were generated with 6X using dynamic multileaf collimator (DMLC) and static multileaf collimator (SMLC) with 5, 10 and 15 intensity levels (L). Integral dose, volume receiving 5 Gy, number of monitor units (MU) is compared against DMLC. The mean difference in the MU delivered per fraction between 5, 10 and 15 L SMLC and DMLC was -13.25% (P < 0.001, with paired t test), -11.82% (P < 0.001) and -10.81% (P < 0.001), respectively. The mean difference in the integral dose with 5, 10 and 15 L compared to DMLC was -2.96% (P < 0.001), -2.67% (P = 0.016) and -0.39% (P = 0.430), respectively. However, the difference in low-dose volume (V5Gy) was statistically insignificant with mean difference of 0.60% (P = 0.23), 1.18% (P = 0.017) and 1.70% (P = 0.078), respectively for 5, 10 and 15 L compared to DMLC. Our results show that while choosing the IMRT delivery technique using conventional MLC the concerns about integral dose and volume receiving very low doses such as 5 Gy can be ignored.

Normal tissue complication probability of fibrosis in radiotherapy of breast cancer: accelerated partial breast irradiation vs conventional external-beam radiotherapy.

AIMS: Radiotherapy forms an integral part of breast-conserving treatment in early-stage breast cancer. Subcutaneous fibrosis of the treated breast is an important late effect in whole-breast irradiation. The aim of this study was to compare the normal tissue complication probability (NTCP) for radiation-induced fibrosis in treated breast using accelerated partial-breast irradiation (APBI) vs conventional treatment. MATERIALS AND METHODS: Ten postoperative early-stage breast cancer patients (T1N0M0) were included in this dosimetric analysis. APBI treatment was planned using conformal radiotherapy technique and conventional treatment plans included two tangential portals. All the APBI treatment plans were made with five non-coplanar beams with 6 MV photons. The prescription dose was 38 Gy in 10 fractions for the APBI treatments and 50 Gy in 25 fractions, followed by a boost dose of 16 Gy in 8 fractions, for the conventional treatments. We used Lyman's relative-seriality model and the breast fibrosis NTCP model fitting parameters for the study. RESULTS: The equivalent uniform dose (EUD) was 30.09 Gy and 50.79 Gy in APBI and conventional treatment, respectively. The mean NTCP values for ipsilateral breast fibrosis in APBI and conventional treatment were 0.51 and 25.66%, respectively. Using the paired t-test, a statistically significant difference was seen in the breast fibrosis NTCP values for APBI vs conventional treatment (P < 0.001). CONCLUSIONS: APBI reduces the ipsilateral breast fibrosis compared to conventional whole-breast treatment in early-stage breast cancer.

Adenoid cystic carcinoma of the trachea treated with PET-CT based intensity modulated radiotherapy.

Primary tumors of the trachea are rare and are usually malignant in adults and benign in children. Adenoid cystic carcinoma, which is of salivary gland origin, account for about one thirds of adult primary tracheal tumors. A 49-year-old gentleman presented to us after undergoing a pneumonectomy elsewhere. Computed tomography scan of the thorax at our hospital showed a residual disease in the primary site, size of which was same as that in the preoperative scan. Because there was a compromised respiratory reserve due to pneumonectomy we decided to keep the radiation dose to the remaining lung as low as possible. We treated him by positron emission tomography-computed tomography (PET-CT) directed intensity modulated radiation therapy to a dose of 60 Gy in 30 Fractions over 6 weeks on a linear accelerator. PET helped in exact localization of the target on the planning CT. He tolerated the treatment very well. PET-CT done 1 year posttreatment showed no residual disease. Presently he is disease free with good pulmonary reserve.

Variation in the isocentre of a Philips linear accelerator (SL-20) used for stereotactic radiosurgery/stereotactic radiotherapy.

Stereotactic irradiation, either in the form of stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) of brain lesions requires high precision and submillimetre accuracy in the isocentre, the main determinants being gantry and couch rotations. It is thus necessary to evaluate the isocentre variation due to gantry and couch rotations in the particular setup for SRS/SRT. This paper describes variation in the isocentre of a Philips (now Elekta) SL-20 linear accelerator modified for adapting a couch-mounted radiosurgery system. By considering the isocentre as defined by a mechanical index as the standard, the variations in the isocentre of the linear accelerator were independently measured for the gantry and for couch rotations. The variation in the isocentre for gantry rotation was found to be between 0.1 mm and 0.9 mm, conforming to the submillimetre accuracy required for SRS/SRT. However, the isocentre variation due to couch rotation varied considerably, possibly because the couch is of the RAM type. The isocentre variation due to couch rotation is rectified by microadjusting the couch mount at the time of treatment using a laser target localizing frame. It is our conclusion that a modified linear accelerator can be used for performing SRS/SRT after careful and separate evaluation of the isocentre stability due to gantry and couch rotations.

Morphology and morphometry of motor endings on macaque intrafusal fibers.

The ultrastructural studies have shown three types of motor endings in the macaque intrafusal fibers: 1) unindented axon terminals with smooth or shallowly folded postsynaptic membrane; 2) indented terminals with few postsynaptic folds; and 3) indented terminals with heavily folded postsynaptic membrane. The terminals on bag 1 and chain fibers were generally more indented than those on the bag 2 fibers. Deeply indented terminals with highly folded postsynaptic membranes were noticed on the bag 1 and chain endings in spindles from lumbrical but not the biceps muscle. In the individual intrafusal fibers from the biceps and lumbrical spindles, the degree of indentation did not correlate with the extent of postsynaptic folding (P greater than .01). Endings on bag 1 and chain fibers in the lumbrical spindles showed a positive correlation between indentation of terminals and their distance from the primary sensory endings (P less than .01), whereas the lumbrical bag 2 endings and the biceps intrafusal endings did not (P greater than .01). The shape of the intrafusal motor endings thus is independent of their location but dependent on the type of intrafusal fibers.

Membrane abnormality in malignant hyperthermia.

In this study we report on the effect of halothane exposure on the skeletal muscle membrane and calcium localization in 9 patients with confirmed susceptibility to malignant hyperthermia and compare them with 11 non-susceptible cases of malignant hyperthermia. Two normal muscle specimens with physiologically induced muscle contractures were also included for comparison. Halothane exposure in malignant hyperthermia-susceptible cases showed severe muscle contractures, definite breaks in the plasma membrane with peroxidase penetration, and large number of calcium granules within the mitochondria and sarcoplasmic reticulum. Malignant hyperthermia-non-susceptible cases and muscle with physiological contractures did not show discontinuity of the plasma membrane or excessive calcium deposits. Based on these findings we conclude that the halothane exposure in malignant hyperthermia-susceptible patients causes breaks in the muscle plasma membrane.

Effect of fiber types, fascicle size and halothane on caffeine contractures in rat muscles.

Caffeine contractures were recorded from thin bundles and whole extensor digitorum longus (EDL) and soleus muscles of rat, and correlated with preparation size and fiber types. Thin bundles were more sensitive to caffeine and halothane than whole muscles, and bundles of 100% type I fibers were more sensitive than bundles of 100% type II fibers. Magnitude of contracture had significant correlation with maximal tetanic tension, total number of fibers, thickness of the preparation, and proportion of type I fibers. These results suggest that fascicle size and fiber types significantly affect results of in vitro contracture test for susceptibility to malignant hyperthermia.

Variability of mitochondrial cytochemistry in human neuromuscular diseases.

This study describes mitochondrial cytochemistry with reference to cytochrome c oxidase and NADH oxidase activities as well as calcium localization at subcellular level in a variety of human mitochondrial disorders. The enzyme activities, calcium homeostasis, and myofibrillary architecture were retained in the lipid storage myopathies with carnitine and carnitine palmityl transferase deficiency. The loss of enzyme reaction, excessive Ca++ deposit, and myonecrosis were the features of the group comprised of a variety of disorders with mitochondrial pathology (Kearns-Sayre's syndrome, chronic progressive ophthalmoplegia, polymyositis, neurogenic atrophy, and fascioscapulo humeral dystrophy). Based on these and our previous experimental study (Shah et al., 1985), we suggest that the human mitochondrial disorders may be grouped into two types: one in which the morphologically altered mitochondria retain the enzyme activities and Ca++ homeostasis and the other in which the altered mitochondria associated with muscle necrosis represent the loss/reduction of the enzyme activities as well as Ca++ homeostasis.

Attachments of human intrafusal fibers.

The human intrafusal fibers have two major types of attachments: (1) extracapsular, involving the bag and long chain fibers which tapered into the extrafusal endomysium; and (2) intracapsular, involving only the short chain fibers which attached to the outer or inner capsule as well as to the bag, and other chain fibers. At all the attachment sites except the interfiber attachments, the intrafusal fibers showed alterations in the basement and plasma membrane, streaming of the Z band, and rod bodies. This profile was similar to the myotendinous junctions. The terminal sarcomere segment consisted of the actin filaments, thickening of the plasma membrane, and folded basal lamina. The interfiber attachments were of two types--the gap and tight junctions. There were thus two major functional types of attachment, the myotendinous type contacts which were mechanical and the interfiber attachments which represent electrical continuity between the two chain fibers.