K.Y. Cheung

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.

Phase II study of neoadjuvant carboplatin and paclitaxel followed by radiotherapy and concurrent cisplatin in patients with locoregionally advanced nasopharyngeal carcinoma: Therapeutic monitoring with plasma Epstein-Barr virus DNA

PURPOSE To assess the efficacy of neoadjuvant paclitaxel and carboplatin (TC) followed by concurrent cisplatin and radiotherapy (RT) in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) and to monitor treatment response with plasma Epstein-Barr virus (EBV) DNA. PATIENTS AND METHODS Thirty-one patients with International Union Against Cancer stages III and IV undifferentiated NPC had two cycles of paclitaxel (70 mg/m2 on days 1, 8, and 15) and carboplatin (area under the curve 6 mg/mL/min on day 1) on a 3-weekly cycle, followed by 6 to 8 weeks of cisplatin (40 mg/m2 weekly) and RT at 66 Gy in 2-Gy fractions. Plasma EBV DNA was measured serially using the real-time quantitative polymerase chain reaction method. Results All patients completed planned treatment. Response to neoadjuvant TC was as follows: 12 patients (39%) achieved partial response (PR) and 18 achieved (58%) complete response (CR) in regional nodes; five patients (16%) achieved PR and no patients achieved CR in nasopharynx. At 6 weeks after RT, one patient (3%) achieved PR and 30 patients (97%) achieved CR in regional nodes, and 31 patients (100%) achieved CR in nasopharynx; 29 patients (93%) had EBV DNA level of less than 500 copies/mL. Neoadjuvant TC was well tolerated, and the most common acute toxicity of cisplatin plus RT was grade 3 mucositis (55%). At median follow-up of 33.7 months (range, 7 to 39.3 months), six distant and three locoregional failures occurred. Plasma EBV DNA level increased significantly in eight of nine patients who experienced treatment failure but did not increase in those who did not. The 2-year overall and progression-free survival rates were 91.8% and 78.5%, respectively. CONCLUSION This strategy was feasible and resulted in excellent local tumor control. Serial plasma EBV DNA provides a noninvasive method of monitoring response in NPC.

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.

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.

Feasibility of using interpolated contours of targets and organs-at-risk in intensity-modulated radiation therapy treatment planning for advanced-stage NPC

Background & Purpose: It is time consuming to contour numerous structures on CT images during intensity-modulated radiation therapy (IMRT) planning for nasopharyngeal carcinoma (NPC). The present study compares the dosimetry of using ‘interpolated’ contours and ‘real’ contours in advanced-stage NPC. Methods & Materials: Twenty NPC patients with T3-4 tumors were selected and contours of targets and OARs were delineated on consecutive CT images. For each patient, a reference (REF) IMRT plan was generated based on these ‘real’ contours. An investigative (INV) IMRT plan was generated with the same planning protocol but based on ‘interpolated’ contours that were reformed after deleting the contours on alternate slices and replacing the deleted contours by the interpolated contours of the adjacent slices. The dose-endpoints of targets and OARs between two plans were compared. Results: For both the gross tumor volume (GTV) and planning target volume (PTV), all cases in both plans achieved 95% volume receiving the prescribed dose, and less than 1% volume receiving <93% dose, except for the PTV in the INV plan for 1 case. For the brainstem, the mean maximum dose (Dmax) (53.6Gy vs 53.8Gy, p=0.443) was not significantly increased in the INV plans. For the spinal cord, the Dmax (43.5Gy vs 44.0Gy, p=0.026) was significantly increased in the INV plan and the Dmax exceed 45Gy in 5/20 cases in both plans. There was no significant difference between the two plans in the mean dose of the parallel-sensitive organs. Conclusions: The use of interpolated contours resulted in a modest reduction in the minimum dose of the targets and an increase in the maximum dose of the brainstem and spinal cord, however, the small magnitude of difference is unlikely to be clinically significant. Despite the limitation of small sample size, further investigation of this timing-saving technique is justified..

Status of Medical Physics in Asia Pacific Region

According to a large scale surveys conducted in year 2011 by an ad hoc medical physics working group, the Asia and Pacific region has about 3864 radiation oncology medical physicists. This is a significant increase from about 2410 found in a 2008 survey. The number of imaging medical physicists in the region is rather uncertain as the two surveys did not cover specifically medical physicists engaged in imaging physics work. It is estimated that about 10% of the medical physicists in AFOMP are engaged in imaging work. This number is expected to increase as imaging physics is gaining momentum due to increasing application of imaging techniques in radiation therapy. Despite of the significant increase in the number of medical physicists in radiation oncology over the past three years, the mean ratio of the number of radiation oncology medical physicist to MV treatment machine in the region remained basically unchanged due to a corresponding increase in the number of treatment machines in the region. The regional mean ratio was 1.04 in 2008 against 1.14 in 2011. The national ratio varied significantly between countries from 0.64 in a developing country to 2.13 in a developed country. The survey data indicated that there were much shortage in both radiotherapy treatment equipment and medical physicists in the developing countries in the region. According to a large scale global survey conducted by IAEA during late 2009 to early 2010 on education, training and professional development of medical physicists, most of the countries in the region demanded a master degree as the entry requirement for the medical physics profession. However, formal clinical training was available in only 9 countries with duration of training varied between 1 to 4 years. Four of these countries adapted the IAEA clinical training programs in radiation oncology physics and imaging physics. In countries where formal clinical trainings were not available, informal on the job trainings were given to newly appointed medical physicists. National systems for professional certification of medical physicist were established in countries where formal clinical trainings are available. Voluntary CPD systems were also established in these countries. The survey data indicated a large variation in the clinical training and professional development of medical physicists in the region. Such degree of disparity in qualification and competency is considered as unsatisfactory and can have negative impact on the standard of practice and professional status of medical physicists. External audit of training and professional certification systems is considered by some countries as useful in improving the professional status of certified medical physicists and also in getting supports for training resources. Medical physicists in the region are looking into standardization of training and professional competence and are exploring the possibility of achieving this through independent accreditation. With this objective, six medical physics organizations in the region have become chartered members of the International Medical Physicist Certification Board (IMPCB) and are enthusiastically working to have their national certification systems accredited by IMPCB or other accreditation bodies.

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.

SU-FF-T-191: Dosimetric Improvement in Treatment of Advanced-Stage Nasopharyngeal Carcinoma Using Split Organ Delineation Approach and Multiple Virtual Organs Generation Approach in Intensity-Modulated Radiation Therapy Dose Optimization

Purpose: To evaluate the efficacy of improving target coverage and sparing of the organs‐at‐risk (OARs) using split organ delineation approach (SODA) and multiple virtual organs generation approach (MVOGA) in planning of intensity‐modulated radiation therapy(IMRT) for advanced‐stage nasopharyngeal carcinoma (NPC) Method and Materials: Twenty NPC patients with T3‐4 tumors were selected. For each patient, a reference (REF) IMRT plan was generated with optimized target coverage and sparing of OARs. An investigative plan (INV) was also generated with the same planning protocol as the REF plan, with the exceptions that first, the contours of the parotid glands and temporal lobes were split into target‐overlapping and non‐overlapping regions, and second, multiple virtual organs were created to represent the normal tissues (such as segments of mucosa and muscles that are not conventionally designated as OARs). Each of the split and virtual organs was assigned with independent dose‐volume constraints. The REF and INV plans were compared with respect to the conformity index (CI), and dose‐endpoints of the OARs using paired‐t test. Results: The INV plan was superior to the REF plans in terms of the CI of the GTVs (0.55 vs 0.50, p = 0.017), CI of the PTVs (0.79 vs 0.70, p =0.000), and the minimum dose of the PTVs (47.2Gy vs 44.8Gy, p=0.008). For the OARs, there was significant reduction in dose in the INV plan in terms of the mean dose (max 4.6Gy, p=0.003) to the parotid glands, the maximum dose (max 10Gy, p<0.024) and the mean dose (max 6Gy, p<0.000) to the virtual organs.Conclusion: Using a split organ delineation approach and multiple virtual organs generation approach in IMRTtreatment planning, further dosimetric improvement in target coverage in the regions that overlapped with organs‐at‐risk can be achieved, together with sparing of the parotid glands and normal surrounding tissues.