Lymphocyte dynamics during and after chemo-radiation correlate to dose and outcome in stage III NSCLC patients undergoing maintenance immunotherapy.

PURPOSE: We investigated the dynamics of lymphocyte depletion and recovery during and after definitive concurrent chemoradiotherapy (CCRT), dose to which structures is correlated to them, and how they affect the prognosis of stage III non-small cell lung cancer (NSCLC) patients undergoing maintenance immunotherapy. METHODS AND MATERIALS: In this retrospective study, absolute lymphocyte counts (ALC) of 66 patients were obtained before, during, and after CCRT. Persistent lymphopenia was defined as ALC < 500/µL at 3 months after CCRT. The impact of regional dose on lymphocyte depletion and recovery was investigated using voxel-based analysis (VBA). RESULTS: Most patients (n = 65) experienced lymphopenia during CCRT: 39 patients (59.0%) had grade (G) 3+ lymphopenia. Fifty-nine patients (89.3%) recovered from treatment-related lymphopenia at 3 months after CCRT, whereas 7 (10.6%) showed persistent lymphopenia. Patient characteristics associated with persistent lymphopenia were older age and ALC before and during treatment. In multivariable Cox regression analysis, recovery from lymphopenia was identified as a significant prognostic factor for Progression Free Survival (HR 0.35, 95% CI 0.13-0.93, p = 0.034) and Overall Survival (HR 0.24, 95% CI 0.08-0.68, p = 0.007). Voxel-based analysis showed strong correlation of dose to the upper mediastinum with lymphopenia at the end of CCRT, but not at 3 months after CCRT. CONCLUSION: Recovery from lymphopenia is strongly correlated to improved survival of patients undergoing CCRT and adjuvant immunotherapy, and is correlated to lymphocyte counts pre- and post-CCRT. VBA reveals high correlation of dose to large vessels to lymphopenia at the end of CCRT. Therefore, efforts should be made not only for preventing lymphocyte depletion during CCRT but also for helping lymphocyte recovery after CCRT.

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials.

BACKGROUND: Entrectinib is a potent inhibitor of tropomyosin receptor kinase (TRK) A, B, and C, which has been shown to have anti-tumour activity against NTRK gene fusion-positive solid tumours, including CNS activity due to its ability to penetrate the blood-brain barrier. We present an integrated efficacy and safety analysis of patients with metastatic or locally advanced solid tumours harbouring oncogenic NTRK1, NTRK2, and NTRK3 gene fusions treated in three ongoing, early-phase trials. METHODS: An integrated database comprised the pivotal datasets of three, ongoing phase 1 or 2 clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2), which enrolled patients aged 18 years or older with metastatic or locally advanced NTRK fusion-positive solid tumours who received entrectinib orally at a dose of at least 600 mg once per day in a capsule. All patients had an Eastern Cooperative Oncology Group performance status of 0-2 and could have received previous anti-cancer therapy (except previous TRK inhibitors). The primary endpoints, the proportion of patients with an objective response and median duration of response, were evaluated by blinded independent central review in the efficacy-evaluable population (ie, patients with NTRK fusion-positive solid tumours who were TRK inhibitor-naive and had received at least one dose of entrectinib). Overall safety evaluable population included patients from STARTRK-1, STARTRK-2, ALKA-372-001, and STARTRK-NG (NCT02650401; treating young adult and paediatric patients [aged ≤21 years]), who received at least one dose of entrectinib, regardless of tumour type or gene rearrangement. NTRK fusion-positive safety evaluable population comprised all patients who have received at least one dose of entrectinib regardless of dose or follow-up. These ongoing studies are registered with ClinicalTrials.gov, NCT02097810 (STARTRK-1) and NCT02568267 (STARTRK-2), and EudraCT, 2012-000148-88 (ALKA-372-001). FINDINGS: Patients were enrolled in ALKA-372-001 from Oct 26, 2012, to March 27, 2018; in STARTRK-1 from Aug 7, 2014, to May 10, 2018; and in STARTRK-2 from Nov 19, 2015 (enrolment is ongoing). At the data cutoff date for this analysis (May 31, 2018) the efficacy-evaluable population comprised 54 adults with advanced or metastatic NTRK fusion-positive solid tumours comprising ten different tumour types and 19 different histologies. Median follow-up was 12.9 months (IQR 8·77-18·76). 31 (57%; 95% CI 43·2-70·8) of 54 patients had an objective response, of which four (7%) were complete responses and 27 (50%) partial reponses. Median duration of response was 10 months (95% CI 7·1 to not estimable). The most common grade 3 or 4 treatment-related adverse events in both safety populations were increased weight (seven [10%] of 68 patients in the NTRK fusion-positive safety population and in 18 [5%] of 355 patients in the overall safety-evaluable population) and anaemia (8 [12%] and 16 [5%]). The most common serious treatment-related adverse events were nervous system disorders (three [4%] of 68 patients and ten [3%] of 355 patients). No treatment-related deaths occurred. INTERPRETATION: Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours, and was well tolerated with a manageable safety profile. These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours. These data highlight the need to routinely test for NTRK fusions to broaden the therapeutic options available for patients with NTRK fusion-positive solid tumours. FUNDING: Ignyta/F Hoffmann-La Roche.

Variability in target delineation of cervical carcinoma: A Korean radiation oncology group study (KROG 15-06).

PURPOSE: To determine inter-observer variability in target volume definition of cervical cancer in radical and adjuvant radiotherapy (RT) settings. METHODS: Eight physicians contoured CTVs of 2 patients underwent definitive and postoperative RT. Each volume was analyzed using the individual/median volume ratio and generalized conformity index (CIgen). And center of mass (COM) of each contour was calculated. Expert agreement was quantified using an expectation maximization algorithm for Simultaneous Truth and Performance Level Estimation (STAPLE). RESULTS: For definitive RT, the individual/median volume ratio ranged from 0.51 to 1.41, and CIgen was 0.531. Mean 3-dimensional distances of average to each COM were 7.8 mm. For postoperative RT setting, corresponding values were 0.65-1.38, 0.563, and 5.3 mm. Kappa value of expert agreement was 0.65 and 0.67, respectively. STAPLE estimates of the sensitivity, specificity, and kappa measures of inter-physician agreement were 0.73, 0.98, and 0.65 for the definitive and 0.75, 0.98, and 0.67 for the adjuvant radiotherapy setting. The largest difference was observed in the superior-inferior direction, particularly in the upper vagina and the common iliac area. CONCLUSION: As there was still some variability in target delineation, more detailed guidelines for target volume delineation and continuing education would help to reduce this uncertainty.

Dose-Response Relationship between Radiation Dose and Loco-regional Control in Patients with Stage II-III Esophageal Cancer Treated with Definitive Chemoradiotherapy.

PURPOSE: The correlation between radiation dose and loco-regional control (LRC) was evaluated in patients with stage II-III esophageal cancer treated with definitive concurrent chemoradiotherapy (CRT). MATERIALS AND METHODS: Medical records of 236 stage II-III esophageal cancer patients treated with definitive CRT at Yonsei Cancer Center between 1994 and 2013 were retrospectively reviewed. Among these, 120 received a radiation dose of < 60 Gy (standard-dose group), while 116 received ≥ 60 Gy (high-dose group). The median doses of radiation in the standard- and high-dose groups were 50.4 and 63 Gy, respectively. Concurrent 5-fluorouracil/cisplatin chemotherapy was administered to most patients. RESULTS: There were no differences in patient characteristics between the two groups except for high Karnofsky performance status and lower-thoracic lesions being more prevalent in the standard-dose group. The median progression-free survival (PFS) and overall survival (OS) times were 13.2 months and 26.2 months, respectively. Patients in the high-dose group had significantly better 2-year LRC (69.1% vs. 50.3%, p=0.002), median PFS (16.7 months vs. 11.7 months, p=0.029), and median OS (35.1 months vs. 22.3 months, p=0.043). Additionally, LRC exhibited a dose-response relationship and the complete response rate was significantly higher in the high-dose group (p=0.006). There were no significant differences in treatment-related toxicities between the groups. CONCLUSION: A higher radiation dose (> 60 Gy) is associated with increased LRC, PFS, and OS in patients with stage II-III esophageal cancer treated with definitive CRT.

Analysis of prostate bed motion using an endorectal balloon and cone beam computed tomography during postprostatectomy radiotherapy.

BACKGROUND: The authors conducted this prospective study to analyze the amount of interfractional prostate bed motion (PBM) and quantify its components with the use of an endorectal balloon (ERB). METHODS: A total of 1,348 cone beam computed tomography images from 46 patients who underwent postprostatectomy radiotherapy were analyzed. For the pilot image, electronic portal imaging, guided by skin marks was performed to ensure proper positioning and inflation of the ERB. Then, for bone matching, manual or automatic registration of the planning and each cone beam computed tomography was performed, based on the bony anatomy of the pelvis. Shifts (bony misalignment [BM]) in three directions were recorded at each treatment session. For prostate bed matching, manual matching was conducted based on the anterior rectal wall and the shift (PBM) was recorded. Total setup error was defined as the shift from the skin mark to the prostate bed matching, based on anterior rectal wall stretched by the ERB. PBM was defined as the difference between the total setup error and BM. RESULTS: Systematic errors for the total setup error were 1.0, 1.3, and 1.0 mm in the right-left, anterior-posterior, and superior-inferior directions, with random errors of 1.9, 2.4, and 1.9 mm, respectively. Systematic errors were 1.6, 1.6, and 0.3 mm for BM and 0.8, 1.1, and 0.9 mm for PBM, with random errors of 2.4, 2.5, and 1.1 mm for BM and 1.8, 2.2, and 1.9 mm for PBM. CONCLUSION: The BM was the main component of the total setup error, suggesting that interfractional PBM was well controlled by the ERB device. Planning target volume margins of <5 mm were needed to include 95% of the interfractional variations when using an ERB.

Is Total Knee Arthroplasty a Viable Treatment Option in Octogenarians with Advanced Osteoarthritis?

PURPOSE: This study directly compared clinical assessment scores and short-term systemic complications after total knee arthroplasty (TKA) between a group of patients aged 80 or older (141 patients) and another group of patients aged between 65 and 70 years (616 patients) with advanced osteoarthritis. MATERIALS AND METHODS: We retrospectively investigated 757 osteoarthritic patients who underwent primary TKA from January 2007 to January 2011 with a follow-up of 1 year. The surgery was performed using an extramedullary alignment guide instrument without invasion of the intramedullary canal to decrease embolic load and blood loss. RESULTS: At 1 year after surgery, the mean Knee Society knee score was improved in both groups (from 63.6 to 83.2 in octogenarians and from 68.3 to 89.0 in the younger group) and the level of satisfaction was excellent in both groups (8 in octogenarians and 8.3 in the younger group), even though there was no notable change in function score in the octogenarians (from 61.0 to 61.9 in the octogenarians and from 62.3 to 73.6 in the younger group). The total incidence of systemic complications (3.4% vs. 1.2%, p=0.400) and surgical complications (2.1% vs. 0.5%, p=0.229) showed no significant difference between groups. CONCLUSIONS: TKA yielded favorable clinical outcomes with a comparatively low postoperative complication rate in octogenarians despite the negligible functional improvement.

The application of PET-CT to post-mastectomy regional radiation therapy using a deformable image registration.

BACKGROUND: To evaluate the utility of the preoperative PET-CT using deformable image registration (DIR) in the treatment of patients with locally advanced breast cancer and to find appropriate radiotherapy technique for further adequate treatment of axillary nodal area. METHODS: Sixty-five breast cancer patients who had level II, III axillary or supraclavicular lymph node metastasis on ¹8F-FDG PET-CT and received postoperative radiotherapy after modified radical mastectomy were enrolled. One radiation oncologist contoured normal organs (axillary vessels, clavicular head, coracoids process and humeral head) and involved lymph nodes on PET-CT and simulation CT slices. After contouring, deformable image registration of PET-CT on simulation CT was carried out. To evaluate the performance of the DIR, Dice similarity coefficient (DSC) and Center of mass (COM) were used. We created two plans, one was the historically designed three field plan and the other was the modified plan based on the location of axillary lymph node, and we compared the doses that irradiated the axillary lymph nodes. RESULTS: The DSCs for axillary artery, axillary vein, clavicular head, coracoids process and humeral head were 0.43 ± 0.15, 0.39 ± 0.20, 0.85 ± 0.10, 0.72 ± 0.20 and 0.77 ± 0.20, respectively. The distances between the COMs of axillary artery, axillary vein, clavicular head, coracoids process and humeral head in simulation CT and from PET-CT were 13.0 ±7.1, 20.2 ± 11.2, 4.4 ± 6.3, 3.7 ± 6.7, and 9.5 ± 25.0 mm, respectively. In the historically designed plan, only 57.7% of level II lymph nodes received more than 95% of prescribed dose and the coverage was improved to 70.0% with the modified plan (p < 0.01). For level III lymph nodes, the volumes received more than 95% of prescribed dose were similar in both plans (96.8 % vs 97.9%, p = 0.35). CONCLUSION: Deformable image registration of PET-CT on simulation CT was helpful in the identification of the location of the preoperatively involved axillary lymph node. Historically designed three-field plan was not adequate to treat the axillary level II lymph node area. Novel treatment technique based on the location of axillary lymph node from PET-CT using DIR can result in more adequate coverage of nodal area.

Our experiences with robot-assisted laparoscopic radical cystectomy: orthotopic neobladder by the suprapubic incision method.

PURPOSE: To report our technique for and experience with robot-assisted laparoscopic radical cystectomy (RARC) with orthotopic neobladder (ON) formation in a cohort of bladder cancer patients. MATERIALS AND METHODS: Between December 2007 and December 2011, a total of 35 patients underwent RARC. The patients' mean age was 63.3 years and their mean body mass index was 23.7 kg/m(2). Thirty patients had a clinical stage of T2 or higher. Postoperative mean follow-up duration was 25.5 months. In 5 patients, a 4-cm midline infraumbilical skin incision was made for an ileal conduit (IC) and the stoma formation was similar to the open procedure. In 30 patients undergoing the ON procedure, the skin for specimen removal and extracorporeal enterocystoplasty was incised infraumbilically in the early 5 cases with redocking (ON-I) and suprapubically in the latter 25 cases without redocking (ON-S). RESULTS: The mean operative times of the IC, ON-I, and ON-S groups were 442.5, 646.0, and 531.3 minutes, respectively (p=0.001). Mean console and lymph node dissection time were not significantly different between the groups. Mean urinary diversion times in each group were 68.8, 125.0, and 118.8 minutes, respectively (p=0.001). In the comparison between the ON-I and ON-S group, only operative time was significant. Four patients required a blood transfusion. We had no cases of intraabdominal organ injury or open conversion. Thiry-three patients (94.2%) had a pathologic stage of T2 or higher. Two patients (5.7%) had lymph node-positive disease. Postoperative complications included ileus (n=4), stricture in the uretero-ileal junction (n=2), and vesicovaginal fistula (n=1). CONCLUSIONS: Our robotic neobladder-suprapubic incision without redocking procedure is easier and more rapid than that of infraumbilical incision with redocking.

Experimental investigation of a moving averaging algorithm for motion perpendicular to the leaf travel direction in dynamic MLC target tracking.

PURPOSE: In dynamic multileaf collimator (MLC) motion tracking with complex intensity-modulated radiation therapy (IMRT) fields, target motion perpendicular to the MLC leaf travel direction can cause beam holds, which increase beam delivery time by up to a factor of 4. As a means to balance delivery efficiency and accuracy, a moving average algorithm was incorporated into a dynamic MLC motion tracking system (i.e., moving average tracking) to account for target motion perpendicular to the MLC leaf travel direction. The experimental investigation of the moving average algorithm compared with real-time tracking and no compensation beam delivery is described. METHODS: The properties of the moving average algorithm were measured and compared with those of real-time tracking (dynamic MLC motion tracking accounting for both target motion parallel and perpendicular to the leaf travel direction) and no compensation beam delivery. The algorithm was investigated using a synthetic motion trace with a baseline drift and four patient-measured 3D tumor motion traces representing regular and irregular motions with varying baseline drifts. Each motion trace was reproduced by a moving platform. The delivery efficiency, geometric accuracy, and dosimetric accuracy were evaluated for conformal, step-and-shoot IMRT, and dynamic sliding window IMRT treatment plans using the synthetic and patient motion traces. The dosimetric accuracy was quantified via a tgamma-test with a 3%/3 mm criterion. RESULTS: The delivery efficiency ranged from 89 to 100% for moving average tracking, 26%-100% for real-time tracking, and 100% (by definition) for no compensation. The root-mean-square geometric error ranged from 3.2 to 4.0 mm for moving average tracking, 0.7-1.1 mm for real-time tracking, and 3.7-7.2 mm for no compensation. The percentage of dosimetric points failing the gamma-test ranged from 4 to 30% for moving average tracking, 0%-23% for real-time tracking, and 10%-47% for no compensation. CONCLUSIONS: The delivery efficiency of moving average tracking was up to four times higher than that of real-time tracking and approached the efficiency of no compensation for all cases. The geometric accuracy and dosimetric accuracy of the moving average algorithm was between real-time tracking and no compensation, approximately half the percentage of dosimetric points failing the gamma-test compared with no compensation.

Inter- and intra-observer variability in contouring of the prostate gland on planning computed tomography and cone beam computed tomography.

PURPOSE: To investigate inter-/intra-observer variability in defining the prostate by use of planning computed tomography (PCT) and cone beam CT (CBCT) with magnetic resonance image (MRI) as guidance prior to the introduction of an adaptive radiotherapy for prostate cancer. MATERIAL AND METHODS: We reviewed PCT and firstly acquired CBCT datasets of each ten patients with prostate cancer. Three physicians independently delineated the prostate based on PCT and CBCT with MRI as guidance, allowing determination of inter-physician variability. Two physicians repeated prostate contouring three times in total to investigate intra-physician variability. We compared delineated prostate volumes in terms of the generalized conformity index (CI(gen)), maximum variation ratio (MVR), and center of mass (COM). RESULTS: There were no significant inter-/intra-observer differences in the estimation of prostate volume on both PCT and CBCT. For both inter- and intra-observer variability in contouring the prostate gland, there were no significant differences in MVR between PCT and CBCT. The CI(gen) for inter-observer variability was 0.74 by PCT and 0.69 by CBCT. The CI(gen) for intra-observer variability on PCT and CBCT was 0.84 and 0.81 for observer 2 and 0.76 and 0.73 for observer 3. COM analyses showed that the greatest inter-/intra-observer variability was in the measurement of the prostate apex and base. With respect to CI(gen) and COM analysis for the inter-observer variability, more precise delineation of the prostate was possible on PCT than CBCT. More precise contouring in terms of both CI(gen) and COM was demonstrated by observer 2 than observer 3. CONCLUSIONS: Despite some ambiguity in apex and base level, there was a good consistency in delineating the gland on CBCT plus MRI-guided modification both among/within observer(s), without any significant difference from the consistency in defining the prostate on PCT. This study provides a framework for future studies of CBCT imaging of the prostate.

Real-time dynamic MLC tracking for inversely optimized arc radiotherapy.

BACKGROUND AND PURPOSE: Motion compensation with MLC tracking was tested for inversely optimized arc radiotherapy with special attention to the impact of the size of the target displacements and the angle of the leaf trajectory. MATERIALS AND METHODS: An MLC-tracking algorithm was used to adjust the MLC positions according to the target movements using information from an optical real-time positioning management system. Two plans with collimator angles of 45 degrees and 90 degrees , respectively, were delivered and measured using the Delta(4)(R) dosimetric device moving in the superior-inferior direction with peak-to-peak displacements of 5, 10, 15, 20 and 25 mm and a cycle time of 6s. RESULTS: Gamma index evaluation for plan delivery with MLC tracking gave a pass rate higher than 98% for criteria 3% and 3 mm for both plans and for all sizes of the target displacement. With no motion compensation, the average pass rate was 75% for plan 1 and 70% for plan 2 for 25 mm peak-to-peak displacement. CONCLUSION: MLC tracking improves the accuracy of inversely optimized arc delivery for the cases studied. With MLC tracking, the dosimetric accuracy was independent of the magnitude of the peak-to-peak displacement of the target and not significantly affected by the angle between the leaf trajectory and the target movements.

Integration of real-time internal electromagnetic position monitoring coupled with dynamic multileaf collimator tracking: an intensity-modulated radiation therapy feasibility study.

PURPOSE: Continuous tumor position measurement coupled with a tumor tracking system would result in a highly accurate radiation therapy system. Previous internal position monitoring systems have been limited by fluoroscopic radiation dose and low delivery efficiency. We aimed to incorporate a continuous, electromagnetic, three-dimensional position tracking system (Calypso 4D Localization System) with a dynamic multileaf collimator (DMLC)-based dose delivery system. METHODS AND MATERIALS: A research version of the Calypso System provided real-time position of three Beacon transponders. These real-time three-dimensional positions were sent to research MLC controller with a motion-tracking algorithm that changed the planned leaf sequence. Electromagnetic transponders were embedded in a solid water film phantom that moved with patient lung trajectories while being irradiated with two different plans: a step-and-shoot intensity-modulated radiation therapy (S-IMRT) field and a dynamic IMRT (D-IMRT) field. Dosimetric results were recorded under three conditions: no intervention, DMLC tracking, and a spatial gating system. RESULTS: Dosimetric accuracy was comparable for gating and DMLC tracking. Failure rates for gating/DMLC tracking are as follows: +/-3 cGy 10.9/ 7.5% for S-IMRT, 3.3/7.2% for D-IMRT; gamma (3mm/3%) 0.2/1.2% for S-IMRT, 0.2/0.2% for D-IMRT. DMLC tracking proved to be as efficient as standard delivery, with a two- to fivefold efficiency increase over gating. CONCLUSIONS: Real-time target position information was successfully integrated into a DMLC effector system to modify dose delivery. Experimental results show both comparable dosimetric accuracy as well as improved efficiency compared with spatial gating.

Brain metastases from hepatocellular carcinoma: prognostic factors and outcome: brain metastasis from HCC.

Brain metastases from hepatocellular carcinoma are extremely rare. The objectives of the current study were to assess the natural history, outcome, and possible prognostic factors in patients with brain metastases from hepatocellular carcinoma. Between 1995 and 2006, 6,919 patients with hepatocellular carcinoma were treated at Yonsei University Health System. Of those, 62 (0.9%) had a diagnosis of brain metastasis. We carried out a retrospective review of these 62 patients and performed a statistical analysis. The median age at the time patients were diagnosed with brain metastasis was 54 years. Forty-seven patients (76%) were male, and 53 patients had hepatitis B. Median time from diagnosis of hepatocellular carcinoma to brain metastasis was 18.2 months, and 5 patients had brain involvement as their initial presentation. Intracranial hemorrhage was frequently associated (54.8%) with brain metastasis. The most common presenting symptoms were motor weakness, mental change, and headache. Metastases were treated with whole-brain radiation therapy (WBRT) alone in 17 patients and gamma knife surgery alone in 10 patients. Six patients underwent surgical resection and 5 patients were treated with surgical resection followed by WBRT. Twenty-four patients (39%) received steroids only. Median survival after diagnosis of brain metastasis was 6.8 weeks (95% confidence interval: 3.8-9.8 weeks). Univariate analysis showed that treatment modality, number of brain lesions, alpha-fetoprotein, ECOG performance score, recursive partitioning analysis (RPA) class, and Child-Pugh classification had a statistically significant impact on survival. In multivariate analysis, treatment modality, number of brain lesions, and Child-Pugh classification were statistically significant prognostic factors for survival. The overall prognosis of patients with brain metastases from hepatocellular carcinoma is extremely poor. Nevertheless, some subsets of patients manifested the most favorable survival criteria (single brain metastasis and good liver function); thus, for at least these patients, treatment may result in an improved survival time.

Dosimetric characteristics of linear accelerator photon beams with small monitor unit settings.

Several studies on the effect of tumor cell killing by dose rate variation have implied that the use of a shorter treatment time is more favorable for intensity modulated radiation therapy (IMRT). Aiming at step-and-shoot IMRT with higher dose rates, the stabilities of beam output and profiles with small monitor unit (MU) settings were investigated for various dose rates. With the use of a Varian 21EX (Varian Medical Systems Inc., Palo Alto, CA), static and step-and-shoot IMRT beam output along with profiles were measured by use of an ion chamber and a two-dimensional diode array detector as a function of monitor units and dose rates. For a static case, as the MU approached 1, the beam output increased up to 2% for 300 MU/min and 4.5% for 600 MU/min, showing a larger overdose as the dose rate increased. Deterioration of the beam symmetry and flatness were also observed as the MU decreased to 1 monitor unit. For the step-and-shoot IMRT case, a large dosimetric error of more than 10% was also detected with the use of a small MU segment. However, no definite correlation with the dose rate was observed due to the combined beam start-up effects by the grid pulse and finite communication time between the machine console and multileaf collimator (MLC) controller. For step-and-shoot IMRT with higher dose rates, beam output and beam profile stability with small MU needs to be checked, and adequate MU limitation where segments are not allowed need to be reflected in the step-and-shoot IMRT planning.

Monte Carlo-based treatment planning for a spoiler system with experimental validation using plane-parallel ionization chambers.

A beam spoiler is often used to increase the build-up dose near the surface for treatment of superficial treatment areas. Photon-beam spoilers produce a large amount of contaminant electrons, conditions for which standard, commercial treatment-planning system dose-calculation algorithms are inadequate for producing accurate dose calculations. In this study, we implemented a Monte Carlo (MC) dose-calculation algorithm for this spoiler system. With and without a spoiler of 1 cm Lucite, depth doses and transverse profiles in the build-up region were measured for field sizes of 5 x 5 cm2 and 10 x 10 cm2 at the spoiler-to-surface distances (STSDs) of 6, 10 and 15 cm. An Attix chamber and a Markus chamber were used for depth doses, whereas a diode detector was used for transverse profiles. An MC simulation using BEAM/DOSXYZ was used to compare the calculated and the measured data. The MC calculations agreed with the Attix chamber measurements within 2% for all STSDs and field sizes, whereas the Markus data--even with corrections made-showed a discrepancy of about 3.5% with a maximum difference of 7.3% for a field size of 10 x 10 cm2 at an STSD of 6 cm. The MC treatment-planning system was successfully applied to a head-and-neck case using 6 MV photon beams with a beam spoiler.

Report of a study on IMRT planning strategies for ethmoid sinus cancer.

AIM: This communication reviews the planning strategies and dose statistics of nine IMRT plans generated for a complex head and neck case. PATIENT AND METHOD: An ethmoid sinus cancer case was sent as an IMRT planning task to all participants of the ESTRO course on "IMRT and Other Conformal Techniques in Practice", held in Amsterdam in June 2001. RESULTS: Nine IMRT plans were generated for the case, the majority of the plans generated with commercial planning systems. The number of beam incidences ranged between four and eleven, while five of the nine beam setups were coplanar. The planning target volume dose homogeneity was inversely correlated with the degree of sparing of the surrounding organs at risk. CONCLUSION: IMRT strategies for complex head and neck cases, such as ethmoid sinus cancer, can be strikingly different in various aspects, such as beam setup, total number of segments, PTV dose coverage and dose statistics for organs at risks.