Hiroki Shirato

Precise and real-time measurement of 3D tumor motion in lung due to breathing and heartbeat, measured during radiotherapy.

PURPOSE In this work, three-dimensional (3D) motion of lung tumors during radiotherapy in real time was investigated. Understanding the behavior of tumor motion in lung tissue to model tumor movement is necessary for accurate (gated or breath-hold) radiotherapy or CT scanning. METHODS Twenty patients were included in this study. Before treatment, a 2-mm gold marker was implanted in or near the tumor. A real-time tumor tracking system using two fluoroscopy image processor units was installed in the treatment room. The 3D position of the implanted gold marker was determined by using real-time pattern recognition and a calibrated projection geometry. The linear accelerator was triggered to irradiate the tumor only when the gold marker was located within a certain volume. The system provided the coordinates of the gold marker during beam-on and beam-off time in all directions simultaneously, at a sample rate of 30 images per second. The recorded tumor motion was analyzed in terms of the amplitude and curvature of the tumor motion in three directions, the differences in breathing level during treatment, hysteresis (the difference between the inhalation and exhalation trajectory of the tumor), and the amplitude of tumor motion induced by cardiac motion. RESULTS The average amplitude of the tumor motion was greatest (12 +/- 2 mm [SD]) in the cranial-caudal direction for tumors situated in the lower lobes and not attached to rigid structures such as the chest wall or vertebrae. For the lateral and anterior-posterior directions, tumor motion was small both for upper- and lower-lobe tumors (2 +/- 1 mm). The time-averaged tumor position was closer to the exhale position, because the tumor spent more time in the exhalation than in the inhalation phase. The tumor motion was modeled as a sinusoidal movement with varying asymmetry. The tumor position in the exhale phase was more stable than the tumor position in the inhale phase during individual treatment fields. However, in many patients, shifts in the exhale tumor position were observed intra- and interfractionally. These shifts are the result of patient relaxation, gravity (posterior direction), setup errors, and/or patient movement.The 3D trajectory of the tumor showed hysteresis for 10 of the 21 tumors, which ranged from 1 to 5 mm. The extent of hysteresis and the amplitude of the tumor motion remained fairly constant during the entire treatment. Changes in shape of the trajectory of the tumor were observed between subsequent treatment days for only one patient. Fourier analysis revealed that for 7 of the 21 tumors, a measurable motion in the range 1-4 mm was caused by the cardiac beat. These tumors were located near the heart or attached to the aortic arch. The motion due to the heartbeat was greatest in the lateral direction. Tumor motion due to hysteresis and heartbeat can lower treatment efficiency in real-time tumor tracking-gated treatments or lead to a geographic miss in conventional or active breathing controlled treatments. CONCLUSION The real-time tumor tracking system measured the tumor position in all three directions simultaneously, at a sampling rate that enabled detection of tumor motion due to heartbeat as well as hysteresis. Tumor motion and hysteresis could be modeled with an asymmetric function with varying asymmetry. Tumor motion due to breathing was greatest in the cranial-caudal direction for lower-lobe unfixed tumors.

Hypofractionated Stereotactic Radiotherapy (HypoFXSRT) for Stage I Non-small Cell Lung Cancer: Updated Results of 257 Patients in a Japanese Multi-institutional Study

Introduction: Hypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study. Methods: This is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57–180 Gy) based on α/β = 10. Results: During follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p < 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p < 0.05). Conclusions: Although this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC.

Physical aspects of a real-time tumor-tracking system for gated radiotherapy

PURPOSE To reduce uncertainty due to setup error and organ motion during radiotherapy of tumors in or near the lung, by means of real-time tumor tracking and gating of a linear accelerator. METHODS AND MATERIALS The real-time tumor-tracking system consists of four sets of diagnostic X-ray television systems (two of which offer an unobstructed view of the patient at any time), an image processor unit, a gating control unit, and an image display unit. The system recognizes the position of a 2.0-mm gold marker in the human body 30 times per second using two X-ray television systems. The marker is inserted in or near the tumor using image guided implantation. The linear accelerator is gated to irradiate the tumor only when the marker is within a given tolerance from its planned coordinates relative to the isocenter. The accuracy of the system and the additional dose due to the diagnostic X-ray were examined in a phantom, and the geometric performance of the system was evaluated in 4 patients. RESULTS The phantom experiment demonstrated that the geometric accuracy of the tumor-tracking system is better than 1.5 mm for moving targets up to a speed of 40 mm/s. The dose due to the diagnostic X-ray monitoring ranged from 0.01% to 1% of the target dose for a 2.0-Gy irradiation of a chest phantom. In 4 patients with lung cancer, the range of the coordinates of the tumor marker during irradiation was 2.5-5.3 mm, which would have been 9.6-38.4 mm without tracking. CONCLUSION We successfully implemented and applied a tumor-tracking and gating system. The system significantly improves the accuracy of irradiation of targets in motion at the expense of an acceptable amount of diagnostic X-ray exposure.

The management of imaging dose during image-guided radiotherapy: Report of the AAPM Task Group 75

Radiographic image guidance has emerged as the new paradigm for patient positioning, target localization, and external beam alignment in radiotherapy. Although widely varied in modality and method, all radiographic guidance techniques have one thing in common--they can give a significant radiation dose to the patient. As with all medical uses of ionizing radiation, the general view is that this exposure should be carefully managed. The philosophy for dose management adopted by the diagnostic imaging community is summarized by the acronym ALARA, i.e., as low as reasonably achievable. But unlike the general situation with diagnostic imaging and image-guided surgery, image-guided radiotherapy (IGRT) adds the imaging dose to an already high level of therapeutic radiation. There is furthermore an interplay between increased imaging and improved therapeutic dose conformity that suggests the possibility of optimizing rather than simply minimizing the imaging dose. For this reason, the management of imaging dose during radiotherapy is a different problem than its management during routine diagnostic or image-guided surgical procedures. The imaging dose received as part of a radiotherapy treatment has long been regarded as negligible and thus has been quantified in a fairly loose manner. On the other hand, radiation oncologists examine the therapy dose distribution in minute detail. The introduction of more intensive imaging procedures for IGRT now obligates the clinician to evaluate therapeutic and imaging doses in a more balanced manner. This task group is charged with addressing the issue of radiation dose delivered via image guidance techniques during radiotherapy. The group has developed this charge into three objectives: (1) Compile an overview of image-guidance techniques and their associated radiation dose levels, to provide the clinician using a particular set of image guidance techniques with enough data to estimate the total diagnostic dose for a specific treatment scenario, (2) identify ways to reduce the total imaging dose without sacrificing essential imaging information, and (3) recommend optimization strategies to trade off imaging dose with improvements in therapeutic dose delivery. The end goal is to enable the design of image guidance regimens that are as effective and efficient as possible.

Prediction of respiratory tumour motion for real-time image-guided radiotherapy

Image guidance in radiotherapy and extracranial radiosurgery offers the potential for precise radiation dose delivery to a moving tumour. Recent work has demonstrated how to locate and track the position of a tumour in real-time using diagnostic x-ray imaging to find implanted radio-opaque markers. However, the delivery of a treatment plan through gating or beam tracking requires adequate consideration of treatment system latencies, including image acquisition, image processing, communication delays, control system processing, inductance within the motor, mechanical damping, etc. Furthermore, the imaging dose given over long radiosurgery procedures or multiple radiotherapy fractions may not be insignificant, which means that we must reduce the sampling rate of the imaging system. This study evaluates various predictive models for reducing tumour localization errors when a real-time tumour-tracking system targets a moving tumour at a slow imaging rate and with large system latencies. We consider 14 lung tumour cases where the peak-to-peak motion is greater than 8 mm, and compare the localization error using linear prediction, neural network prediction and Kalman filtering, against a system which uses no prediction. To evaluate prediction accuracy for use in beam tracking, we compute the root mean squared error between predicted and actual 3D motion. We found that by using prediction, root mean squared error is improved for all latencies and all imaging rates evaluated. To evaluate prediction accuracy for use in gated treatment, we present a new metric that compares a gating control signal based on predicted motion against the best possible gating control signal. We found that using prediction improves gated treatment accuracy for systems that have latencies of 200 ms or greater, and for systems that have imaging rates of 10 Hz or slower.

Feasibility of insertion/implantation of 2.0-mm-diameter gold internal fiducial markers for precise setup and real-time tumor tracking in radiotherapy.

PURPOSE To examine the feasibility and reliability of insertion of internal fiducial markers into various organs for precise setup and real-time tumor tracking in radiotherapy (RT). MATERIALS AND METHODS Equipment and techniques for the insertion of 2.0-mm-diameter gold markers into or near the tumor were developed for spinal/paraspinal lesions, prostate tumors, and liver and lung tumors. Three markers were used to adjust the center of the mass of the target volume to the planned position in spinal/paraspinal lesions and prostate tumors (the three-marker method). The feasibility of the marker insertion and the stability of the position of markers were tested using stopping rules in the clinical protocol (i.e., the procedure was abandoned if 2 of 3 or 3 of 6 patients experienced marker dropping or migration). After the evaluation of the feasibility, the stability of the marker positions was monitored in those patients who entered the dose-escalation study. RESULTS Each of the following was shown to be feasible: bronchoscopic insertion for the peripheral lung; image-guided transcutaneous insertion for the liver; cystoscopic and image-guided percutaneous insertion for the prostate; and surgical implantation for spinal/paraspinal lesions. Transcutaneous insertion of markers for spinal/paraspinal lesions and bronchoscopic insertion for central lung lesions were abandoned. Overall, marker implantation was successful and was used for real-time tumor tracking in RT in 90 (90%) of 100 lesions. No serious complications related to the marker insertion were noted for any of the 100 lesions. Using three markers surgically implanted into the vertebral bone, the mean +/- standard deviation in distance among the three markers was within 0.2 +/- 0.6 mm (range -1.4 to 0.8) through the treatment period of 30 days. The distance between the three markers gradually decreased during RT in five of six prostate cancers, consistent with a mean rate of volume regression of 9.3% (range 0.015-13%) in 10 days. CONCLUSIONS Internal 2.0-mm-diameter gold markers can be safely inserted into various organs for real-time tumor tracking in RT using the prescribed equipment and techniques. The three-marker method has been shown to be a useful technique for precise setup for spinal/paraspinal lesions and prostate tumors.

Synchronized moving aperture radiation therapy (SMART): average tumour trajectory for lung patients.

Synchronized moving aperture radiation therapy (SMART) is a new technique for treating mobile tumours under development at Massachusetts General Hospital (MGH). The basic idea of SMART is to synchronize the moving radiation beam aperture formed by a dynamic multileaf collimator (DMLC) with the tumour motion induced by respiration. SMART is based on the concept of the average tumour trajectory (ATT) exhibited by a tumour during respiration. During the treatment simulation stage, tumour motion is measured and the ATT is derived. Then, the original IMRT MLC leaf sequence is modified using the ATT to compensate for tumour motion. During treatment, the tumour motion is monitored. The treatment starts when leaf motion and tumour motion are synchronized at a specific breathing phase. The treatment will halt when the tumour drifts away from the ATT and will resume when the synchronization between tumour motion and radiation beam is re-established. In this paper, we present a method to derive the ATT from measured tumour trajectory data. We also investigate the validity of the ATT concept for lung tumours during normal breathing. The lung tumour trajectory data were acquired during actual radiotherapy sessions using a real-time tumour-tracking system. SMART treatment is simulated by assuming that the radiation beam follows the derived ATT and the tumour follows the measured trajectory. In simulation, the treatment starts at exhale phase. The duty cycle of SMART delivery was calculated for various treatment times and gating thresholds, as well as for various exhale phases where the treatment begins. The simulation results show that in the case of free breathing, for 4 out of 11 lung datasets with tumour motion greater than 1 cm from peak to peak, the error in tumour tracking can be controlled to within a couple of millimetres while maintaining a reasonable delivery efficiency. That is to say, without any breath coaching/control, the ATT is a valid concept for some lung tumours. However, to make SMART an efficient technique in general, it is found that breath coaching techniques are required.

Image fusion between 18FDG-PET and MRI/CT for radiotherapy planning of oropharyngeal and nasopharyngeal carcinomas

PURPOSE Accurate diagnosis of tumor extent is important in three-dimensional conformal radiotherapy. This study reports the use of image fusion between (18)F-fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) and magnetic resonance imaging/computed tomography (MRI/CT) for better targets delineation in radiotherapy planning of head-and-neck cancers. METHODS AND MATERIALS The subjects consisted of 12 patients with oropharyngeal carcinoma and 9 patients with nasopharyngeal carcinoma (NPC) who were treated with radical radiotherapy between July 1999 and February 2001. Image fusion between 18FDG-PET and MRI/CT was performed using an automatic multimodality image registration algorithm, which used the brain as an internal reference for registration. Gross tumor volume (GTV) was determined based on clinical examination and 18FDG uptake on the fusion images. Clinical target volume (CTV) was determined following the usual pattern of lymph node spread for each disease entity along with the clinical presentation of each patient. RESULTS Except for 3 cases with superficial tumors, all the other primary tumors were detected by 18FDG-PET. The GTV volumes for primary tumors were not changed by image fusion in 19 cases (89%), increased by 49% in one NPC, and decreased by 45% in another NPC. Normal tissue sparing was more easily performed based on clearer GTV and CTV determination on the fusion images. In particular, parotid sparing became possible in 15 patients (71%) whose upper neck areas near the parotid glands were tumor-free by 18FDG-PET. Within a mean follow-up period of 18 months, no recurrence occurred in the areas defined as CTV, which was treated prophylactically, except for 1 patient who experienced nodal recurrence in the CTV and simultaneous primary site recurrence. CONCLUSION This preliminary study showed that image fusion between 18FDG-PET and MRI/CT was useful in GTV and CTV determination in conformal RT, thus sparing normal tissues.

Tolerance of organs at risk in small-volume, hypofractionated, image-guided radiotherapy for primary and metastatic lung cancers

PURPOSE To determine the organ at risk and the maximum tolerated dose (MTD) of radiation that could be delivered to lung cancer using small-volume, image-guided radiotherapy (IGRT) using hypofractionated, coplanar, and noncoplanar multiple fields. MATERIALS AND METHODS Patients with measurable lung cancer (except small-cell lung cancer) 6 cm or less in diameter for whom surgery was not indicated were eligible for this study. Internal target volume was determined using averaged CT under normal breathing, and for patients with large respiratory motion, using two additional CT scans with breath-holding at the expiratory and inspiratory phases in the same table position. Patients were localized at the isocenter after three-dimensional treatment planning. Their setup was corrected by comparing two linacographies that were orthogonal at the isocenter with corresponding digitally reconstructed images. Megavoltage X-rays using noncoplanar multiple static ports or arcs were used to cover the parenchymal tumor mass. Prophylactic nodal irradiation was not performed. The radiation dose was started at 60 Gy in 8 fractions over 2 weeks (60 Gy/8 Fr/2 weeks) for peripheral lesions 3.0 cm or less, and at 48 Gy/8 Fr/2 weeks at the isocenter for central lesions or tumors more than 3.0 cm at their greatest dimension. RESULTS Fifty-seven lesions in 45 patients were treated. Tumor size ranged from 0.6 to 6.0 cm, with a median of 2.6 cm. Using the starting dose, 1 patient with a central lesion died of a radiation-induced ulcer in the esophagus after receiving 48 Gy/8 Fr at isocenter. Although the contour of esophagus received 80% or less of the prescribed dose in the planning, recontouring of esophagus in retrospective review revealed that 1 cc of esophagus might have received 42.5 Gy, with the maximum dose of 50.5 Gy. One patient with a peripheral lesion experienced Grade 2 pain at the internal chest wall or visceral pleura after receiving 54 Gy/8 Fr. No adverse respiratory reaction was noted in the symptoms or respiratory function tests. The 3-year local control rate was 80.4% +/- 7.1% (a standard error) with a median follow-up period of 17 months for survivors. Because of the Grade 5 toxicity, we have halted this Phase I/II study and are planning to rearrange the protocol setting accordingly. The 3-year local control rate was 69.6 +/- 10.6% for patients who received 48 Gy and 100% for patients who received 60 Gy (p = 0.0442). CONCLUSIONS Small-volume IGRT using 60 Gy in eight fractions is highly effective for the local control of lung tumors, but MTD has not been determined in this study. The organs at risk are extrapleural organs such as the esophagus and internal chest wall/visceral pleura rather than the pulmonary parenchyma in the present protocol setting. Consideration of the uncertainty in the contouring of normal structures is critically important, as is uncertainty in setup of patients and internal organ in the high-dose hypofractionated IGRT.

Residual motion of lung tumours in gated radiotherapy with external respiratory surrogates

Due to respiration, many tumours in the thorax and abdomen may move as much as 3 cm peak-to-peak during radiation treatment. To mitigate motion-induced irradiation of normal lung tissue, clinics have employed external markers to gate the treatment beam. This technique assumes that the correlation between the external surface and the internal tumour position remains constant inter-fractionally and intra-fractionally. In this work, a study has been performed to assess the validity of this correlation assumption for external surface based gated radiotherapy, by measuring the residual tumour motion within a gating window. Eight lung patients with implanted fiducial markers were studied at the NTT Hospital in Sapporo, Japan. Synchronized internal marker positions and external abdominal surface positions were measured during the entire course of treatment. Stereoscopic imaging was used to find the internal markers in four dimensions. The data were used retrospectively to assess conventional external surrogate respiratory-gated treatment. Both amplitude- and phase-based gating methods were investigated. For each method, three gating windows were investigated, each giving 40%, 30% and 20% duty cycle, respectively. The residual motion of the internal marker within these six gating windows was calculated. The beam-to-beam variation and day-to-day variation in the residual motion were calculated for both gating modalities. We found that the residual motion (95th percentile) was between 0.7 and 5.8 mm, 0.8 and 6.0 mm, and 0.9 and 6.2 mm for 20%, 30% and 40% duty cycle windows, respectively. Five of the eight patients showed less residual motion with amplitude-based gating than with phase-based gating. Large fluctuations (>300%) were seen in the residual motion between some beams. Overall, the mean beam-to-beam variation was 37% and 42% from the previous treatment beam for amplitude- and phase-based gating, respectively. The day-to-day variation was 29% and 34% from the previous day for amplitude- and phase-based gating, respectively. Although gating reduced the total tumour motion, the residual motion behaved unpredictably. Residual motion during treatment could exceed that which might have been considered in the treatment plan. Treatment margins that account for motion should be individualized and daily imaging should be performed to ensure that the residual motion is not exceeding the planned motion on a given day.