Ricky Ming Chun Chau

Prospective Randomized Study of Intensity-Modulated Radiotherapy on Salivary Gland Function in Early-Stage Nasopharyngeal Carcinoma Patients

PURPOSE This randomized trial compared the rates of delayed xerostomia between two-dimensional radiation therapy (2DRT) and intensity-modulated radiation therapy (IMRT) in the treatment of early-stage nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS Between November 2001 and December 2003, 60 patients with T1-2bN0-1M0 NPC were randomly assigned to receive either IMRT or 2DRT. Primary end point was incidence of observer-rated severe xerostomia at 1 year after treatment based on Radiotherapy Oncology Group /European Organisation for the Research and Treatment of Cancer late radiation morbidity scoring criteria. Parallel assessment with patient-reported outcome, stimulated parotid flow rate (SPFR), and stimulated whole saliva flow rate (SWSFR) were also made. RESULTS At 1 year after treatment, patients in IMRT arm had lower incidence of observer-rated severe xerostomia than patients in the 2DRT arm (39.3% v 82.1%; P = .001), parallel with a higher fractional SPFR (0.90 v 0.05; P < .0001), and higher fractional SWSFR (0.41 v 0.20; P = .001). As for patients subjective feeling, although a trend of improvement in patient-reported outcome was observed after IMRT, recovery was incomplete and there was no significant difference in patient-reported outcome between the two arms. CONCLUSION IMRT is superior to 2DRT in preserving parotid function and results in less severe delayed xerostomia in the treatment of early-stage NPC. Incomplete improvement in patients subjective xerostomia with parotid-sparing IMRT reflects the need to enhance protection of other salivary glands.

Intensity-modulated radiotherapy in nasopharyngeal carcinoma: dosimetric advantage over conventional plans and feasibility of dose escalation

PURPOSE To compare intensity-modulated radiotherapy (IMRT) with two-dimensional RT (2D-RT) and three-dimensional conformal radiotherapy (3D-CRT) treatment plans in different stages of nasopharyngeal carcinoma and to explore the feasibility of dose escalation in locally advanced disease. MATERIALS AND METHODS Three patients with different stages (T1N0M0, T2bN2M0 with retrostyloid extension, and T4N2M0) were selected, and 2D-RT, 3D-CRT, and IMRT treatment plans (66 Gy) were made for each of them and compared with respect to target coverage, normal tissue sparing, and tumor control probability/normal tissue complication probability values. In the Stage T2b and T4 patients, the IMRT 66-Gy plan was combined with a 3D-CRT 14-Gy boost plan using a 3-mm micromultileaf collimator, and the dose-volume histograms of the summed plans were compared with their corresponding 66-Gy 2D-RT plans. RESULTS In the dosimetric comparison of 2D-RT, 3D-CRT, and IMRT treatment plans, the T1N0M0 patient had better sparing of the parotid glands and temporomandibular joints with IMRT (dose to 50% parotid volume, 57 Gy, 50 Gy, and 31 Gy, respectively). In the T2bN2M0 patient, the dose to 95% volume of the planning target volume improved from 57.5 Gy in 2D-RT to 64.8 Gy in 3D-CRT and 68 Gy in IMRT. In the T4N2M0 patient, improvement in both target coverage and brainstem/temporal lobe sparing was seen with IMRT planning. In the dose-escalation study for locally advanced disease, IMRT 66 Gy plus 14 Gy 3D-CRT boost achieved an improvement in the therapeutic ratio by delivering a higher dose to the target while keeping the normal organs below the maximal tolerance dose. CONCLUSIONS IMRT is useful in treating all stages of nonmetastatic nasopharyngeal carcinoma because of its dosimetric advantages. In early-stage disease, it provides better parotid gland sparing. In locally advanced disease, IMRT offers better tumor coverage and normal organ sparing and allows room for dose escalation.

Final report of a randomized trial on altered-fractionated radiotherapy in nasopharyngeal carcinoma prematurely terminated by significant increase in neurologic complications.

PURPOSE The aim of the present study was to compare the survival, local control and complications of conventional/accelerated-hyperfractionated radiotherapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcinoma (NPC). METHODS AND MATERIALS From February 1993 to October 1995, 159 patients with newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Hos N-stage classification, 1978) were randomized to receive either conventional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfractionated radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the upper cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Arm II, respectively. RESULTS With comparable distribution among the T stages between the two arms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interval, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-free survival, and rates of distant metastasis and regional relapse. Conventional/accelerated-hyperfractionated radiotherapy was associated with significantly increased radiation-induced damage to the central nervous system (including temporal lobe, cranial nerves, optic nerve/chiasma, and brainstem/spinal cord) in Arm II. Although insignificant, radiation-induced cranial nerve(s) palsy (typically involving VIII-XII), trismus, neck soft tissue fibrosis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II. CONCLUSION Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Hos technique, resulted in increased radiation damage to the central nervous system without significant improvement in efficacy.

Three-dimensional dosimetric evaluation of a conventional radiotherapy technique for treatment of nasopharyngeal carcinoma

BACKGROUND AND PURPOSE The aim of this study is to evaluate and delineate the deficiencies in conventional two-dimensional (2-D) radiotherapy planning of nasopharyngeal carcinoma (NPC) treatment and to explore the means for improvement of the existing treatment technique aiming at enhancing local tumor control and reducing treatment complications. METHODS AND MATERIALS Ten patients with NPC sparing the skull base and without intracranial extension or cranial nerve(s) palsy were chosen in the present study. Two sets of CT images for Phases I and II of the radiotherapy treatment were taken with patient immobilized in the flexed-head and the extended-head positions, respectively. Based on the CT images and endoscopic findings, the gross tumor volume (GTV) was defined. The clinical target volume (CTV) circumscribing the GTV was defined according to Hos (Halnan, K.E. (ed.) Treatment of Cancer. London: Chapman and Hall, 1982. pp. 249-268) description of the organs at risk of tumor infiltration. The planning target volume (PTV) was defined by adding a margin to the CTV which catered for geometrical inaccuracies. The field borders and shields were set at standard distances from certain bony landmarks and were drawn on the simulator radiograph. Data on the beams and shield arrangements were then transferred to the planning computer via a digitizer. By applying 3-D volumetric dose calculation using a commercial three-dimensional (3D) treatment planning computer, the dose-volume-histograms (DVHs) of GTV, CTV, PTV and critical normal organs were generated for both phases of Hos treatment technique. The same patients were re-planned using a modified Hos technique which used 3-D beams-eye-view (BEV) in placing the shielding blocks and the same set of DVHs were generated and compared with those obtained from Hos technique. RESULTS The median volumes of GTV, CTV and PTV covered by the 95% isodose in Hos phase I treatment were around 60%. The dose coverage was unsatisfactory in the superior and inferior and the posterolateral regions. In phase II treatment, the median volume of GTV, CTV and PTV covered by the 95% isodose were 99, 96 and 72%, respectively. Even though the dose coverage of the PTV in both phases of treatment were unsatisfactory, radiotherapy with the original Hos technique had consistently produced good local control for NPC. However, there is potential room for enhancing the local control further because after modifying Hos technique by using 3-D BEV customization of the treatment portals, the median volume of the target covered by the 95% isodose was defined as V(95). The V(95) of the PTV during the Phase II treatment was improved by 13%. The 90% of the volume of temporo-mandibular joints and parotid glands were both irradiated to 53 Gy and 43.6 Gy of the total prescribed dose of 66 Gy, respectively, in phase I and II treatments. With the addition of a hypothalamus-pituitary shield to Hos technique, 50% of the volume of optic chiasma and temporal lobes received, respectively, 19.3 Gy and 4.5 Gy. However, small volume of the temporal lobes received a maximum dose (D(max)) of 62.8 Gy (95.2% of 66Gy). Most of the brainstem was shielded from the lateral portals but 5% of its volume received a dose ranging from 25.4 to 50.4Gy. The spinal cord (at C1/C2 level) received a D(max) of 40.8 Gy in phase I and of 4.8 Gy in phase II. After modifying Hos technique by 3-D BEV customization of the treatment portals, the D(max) to the brainstem, the optic chiasma and the temporal lobes could be reduced by 8, 12 and 5%, respectively. CONCLUSIONS Our study indicated that the dose-coverage of the PTV in Hos radiotherapy technique for the early T-stage NPC was less than satisfactory in the superior and inferior and the posterolateral regions. However, in view of the excellent historical local tumor control with Hos technique, we have to postulate that the present definition of CTV (and hence the PTV after adding margins to the CTV) lacks clinical significance and can be improved. It appears that the inclusion of the entire sphenoid sinus floor and both medial and lateral pterygoid muscles in the CTV is not necessary for maximal tumor control in the absence of clinical/radiological evidence of tumor infiltration of these organs. Hos technique can be improved by using 3-D BEV to customize the treatment portals with multileaf collimators or blocks.

The roles of multileaf collimators and micro-multileaf collimators in conformal and conventional nasopharyngeal carcinoma radiotherapy treatments

The purpose of this work is to study the efficacy and limitations of using standard multileaf collimators (MLCs) and micro-multileaf collimators (mMLCs) in the treatment of nasopharyngeal carcinoma (NPC) by conventional and conformal radiotherapy techniques. The penumbra characteristics of MLC, mMLC, and customized block collimated beams are measured with respect to leaf edge angle, beam energy, treatment depth, and field size and compared with those generated by a commercial three-dimensional planning computer system. Upon verification of the planning system, it is used to evaluate the treatment plans generated with these beam shapers for conventional and conformal NPC treatments. The effective penumbra of a MLC beam is strongly influenced by its edge angle, leaf width, and treatment depth. The suitability of standard MLCs in conventional NPC treatments is determined mainly by the edge angle to be used. For conformal NPC treatments involving six or more fields, dose volume histograms comparable to those of customized beam blocks are obtained with a standard MLC. The mMLC does not have the same restrictions as those on standard MLC but is limited to phase II treatment by its small usable field size. Both standard MLCs and mMLCs can be used to replace customized divergent beam blocks in both conventional and conformal NPC treatments. However, a MLC, due to its larger effective penumbra, may be unsuitable for use in cases when the tumor volumes extend very close to the critical normal structures. A mMLC, on the other hand, is limited by its small maximum field size and can only be used for collimating the facial portals in the second phase treatment.

Dosimetric difference amongst 3 techniques: TomoTherapy, sliding-window intensity-modulated radiotherapy (IMRT), and RapidArc radiotherapy in the treatment of late-stage nasopharyngeal carcinoma (NPC)

To investigate the dosimetric difference amongst TomoTherapy, sliding-window intensity-modulated radiotherapy (IMRT), and RapidArc radiotherapy in the treatment of late-stage nasopharyngeal carcinoma (NPC). Ten patients with late-stage (Stage III or IV) NPC treated with TomoTherapy or IMRT were selected for the study. Treatment plans with these 3 techniques were devised according to departmental protocol. Dosimetric parameters for organ at risk and treatment targets were compared between TomoTherapy and IMRT, TomoTherapy and RapidArc, and IMRT and RapidArc. Comparison amongst the techniques was done by statistical tests on the dosimetric parameters, total monitor unit (MU), and expected delivery time. All 3 techniques achieved similar target dose coverage. TomoTherapy achieved significantly lower doses in lens and mandible amongst the techniques. It also achieved significantly better dose conformity to the treatment targets. RapidArc achieved significantly lower dose to the eye and normal tissue, lower total MU, and less delivery time. The dosimetric advantages of the 3 techniques were identified in the treatment of late-stage NPC. This may serve as a guideline for selection of the proper technique for different clinical cases.

Dosimetric Advantages and Superior Treatment Delivery Efficiency of RapidArc over Conventional Intensity-modulated Radiotherapy in High-risk Prostate Cancer Involving Seminal Vesicles and Pelvic Nodes

AIMS To compare the dosimetry and treatment delivery efficiency of RapidArc with conventional intensity-modulated radiotherapy (IMRT) in the treatment of high-risk prostate cancer. MATERIALS AND METHODS Fifteen patients with high-risk localised prostate cancer were studied. Sequential treatment was used. The initial planning target volume (PTV-L) included the prostate, seminal vesicles and pelvic lymphatics, whereas the prostate boost PTV (PTV-P) included the prostate and seminal vesicles only. The total prescription dose was 76 Gy (44 Gy to PTV-L, 32 Gy to PTV-P; 2 Gy/fraction). Two separate planning techniques were generated for each patient: seven static-field IMRT versus two-arc RapidArc. Dose-volume parameters for the organs at risk, conformity index and homogeneity index for the PTVs, the calculated monitor units and treatment delivery time for both techniques were compared. RESULTS RapidArc gave more conformal plans than IMRT for both PTVs. RapidArc gave a higher homogeneity index to the PTV-P and a similar homogeneity index to the PTV-L. The two techniques gave similar dosimetric results for the rectum, bladder and femoral heads. The mean dose (Dmean) and the maximum dose (Dmax) of the bowel space were reduced by 3.06 and 2.83%, respectively, with RapidArc. The V20 Gy, V30 Gy and V40 Gy for healthy tissues were reduced by 7.77, 14.25 and 17.55%, respectively, with RapidArc. The calculated treatment delivery time and monitor units were reduced by 74.09%/60.93% and 68.32%/48.06% for the PTV-L/PTV-P, respectively, with RapidArc. CONCLUSION RapidArc is better than conventional IMRT in terms of dosimetry and delivery efficiency for high-risk prostate cancer.

A Broadly Adaptive Array of Dose-Constraint Templates for Planning of Intensity-Modulated Radiation Therapy for Advanced T-Stage Nasopharyngeal Carcinoma

PURPOSE To develop and validate adaptive dose-constraint templates in intensity-modulated radiotherapy (IMRT) planning for advanced T-stage nasopharyngeal carcinoma (NPC). METHOD AND MATERIALS Dose-volume histograms of clinically approved plans for 20 patients with advanced T-stage NPC were analyzed, and the pattern of distribution in relation to the degree of overlap between targets and organs at risk (OARs) was explored. An adaptive dose constraint template (ADCT) was developed based on the degree of overlap. Another set of 10 patients with advanced T-stage NPC was selected for validation. Results of the manual arm optimization protocol and the ADCT optimization protocol were compared with respect to dose optimization time, conformity indices, multiple-dose end points, tumor control probability, and normal tissue complication probability. RESULTS For the ADCT protocol, average time required to achieve an acceptable plan was 9 minutes, with one optimization compared with 94 minutes with more than two optimizations of the manual arm protocol. Target coverage was similar between the manual arm and ADCT plans. A more desirable dose distribution in the region of overlap between planning target volume and OARs was achieved in the ADCT plan. Dose end points of OARs were similar between the manual arm and ADCT plans. CONCLUSIONS With the developed ADCT, IMRT treatment planning becomes more efficient and less dependent on the planners experience on dose optimization. The developed ADCT is applicable to a wide range of advanced T-stage NPC treatment and has the potential to be applied in a broader context to IMRT planning for other cancer sites.

Dosimetric verification and quality assurance of running‐start‐stop (RSS) delivery in tomotherapy

The purpose of this study was to evaluate the dosimetric profiles and delivery accuracy of running‐start‐stop (RSS) delivery in tomotherapy and to present initial quality assurance (QA) results on the accuracy of the dynamic jaw motion, dosimetric penumbrae of the RSS dynamic jaw and the static jaw were measured by radiographic films. Delivery accuracy of the RSS was evaluated by gamma analysis on film measurements of 12 phantom plans. Consistency in the performance of RSS was evaluated by QA procedures over the first nine months after the installation of the feature. These QA were devised to check: 1) positional accuracy of moving jaws; 2) consistency of relative radiation output collimated by discrete and continuously sweeping jaws; 3) consistency of field widths and profiles. In the longitudinal direction, the dose penumbra in RSS delivery was reduced from 17.3 mm to 10.2 mm for 2.5 cm jaw, and from 33.2 mm to 9.6 mm for 5 cm jaw. Gamma analysis on the twelve plans revealed that over 90% of the voxels in the proximity of the penumbra region satisfied the gamma criteria of 2% dose difference and 2 mm distance‐to‐agreement. The initial QA results during the first nine months after installation of the RSS are presented. Jaw motion was shown to be accurate with maximum encoder error less than 0.42 mm. The consistency of relative output for discrete and continuously sweeping jaws was within 1.2%. Longitudinal radiation profiles agreed to the reference profile with maximum gamma <1 and field width error <1.8%. With the same jaw width, RSS showed better dose penumbrae compared to those from static jaw delivery. The initial QA results on the accuracy of moving jaws, reproducibility of dosimetric output and profiles were satisfactory. PACS number: 87.55.kmThe purpose of this study was to evaluate the dosimetric profiles and delivery accuracy of running-start-stop (RSS) delivery in tomotherapy and to present initial quality assurance (QA) results on the accuracy of the dynamic jaw motion, dosimetric penumbrae of the RSS dynamic jaw and the static jaw were measured by radiographic films. Delivery accuracy of the RSS was evaluated by gamma analysis on film measurements of 12 phantom plans. Consistency in the performance of RSS was evaluated by QA procedures over the first nine months after the installation of the feature. These QA were devised to check: 1) positional accuracy of moving jaws; 2) consistency of relative radiation output collimated by discrete and continuously sweeping jaws; 3) consistency of field widths and profiles. In the longitudinal direction, the dose penumbra in RSS delivery was reduced from 17.3 mm to 10.2 mm for 2.5 cm jaw, and from 33.2 mm to 9.6 mm for 5 cm jaw. Gamma analysis on the twelve plans revealed that over 90% of the voxels in the proximity of the penumbra region satisfied the gamma criteria of 2% dose difference and 2 mm distance-to-agreement. The initial QA results during the first nine months after installation of the RSS are presented. Jaw motion was shown to be accurate with maximum encoder error less than 0.42 mm. The consistency of relative output for discrete and continuously sweeping jaws was within 1.2%. Longitudinal radiation profiles agreed to the reference profile with maximum gamma <1 and field width error <1.8%. With the same jaw width, RSS showed better dose penumbrae compared to those from static jaw delivery. The initial QA results on the accuracy of moving jaws, reproducibility of dosimetric output and profiles were satisfactory. PACS number: 87.55.km.

MO‐D‐BRB‐07: Retrospective RapidArc Dose Reconstruction Based On MLC Dynamic and Delivery Log Files Recorded During Treatment

Purpose: To develop a methodology for retrospectively reconstructing the dose delivered to head‐and‐neck (HN) patients in RapidArc treatment based on dynamic log‐files which record the actual leaf positions, gantry angles, and delivered monitor units (MUs) during the RapidArc delivery. Method and Materials: After a RapidArc treatment was finished, two dynamic log‐files were retrieved from the linear accelerator: (1) MLC log‐file which recorded the actual leaf positions and respective gantry angles every 50 ms and (2) delivery log‐file which recorded the actual delivered MUs and gantry angles at the control points defined in the RapidArc plan. Through the common parameter of gantry angle recorded for both dynamic log files, the actual delivery status such as leaf positions, delivered dose indices, and gantry angles for every control points were re‐constituted. This data was compiled and converted into a DICOM radiotherapy plan (RP) file using in‐house developed software written in MatLab code (Mathworks, Natick, MA). The DICOM RP file was then imported into Eclipse treatment planning system (Varian Medical Systems, Palo Alto, CA) and the actual delivered dose was reconstructed on the on‐treatment CBCT acquired for the patient. Results: A retrospective dose reconstruction procedure has been established for RapidArc and applied to a phantom and two dummy HN cases. For the case in which the tumor shrinkage is minimal, the reconstructed and planned doses were consistent to within 3–5% in high dose region. The DVHs of the target and other organs do not have significant differences. However, large dosimetric changes (10–15%) were observed for the case with tumor shrinkage, indicating the need for re‐planning or adaptive measure to be taken. Conclusion: RapidArc dose reconstruction provides a pragmatic way to probe the actual dose delivery at a particular fraction and represents an indispensable step toward adaptive radiotherapy for this highly conformal treatment.