GTV Volume Research Articles

Dummy run for a phase II study of stereotactic body radiotherapy of T1-T2 N0M0 medical inoperable non-small cell lung cancer

In forthcoming multicentre studies on stereotactic body radiotherapy (SBRT) compliance with volume and dose prescriptions will be mandatory to avoid unnecessary heterogeneity bias. To evaluate compliance in a multicentre setting we used two cases from an ongoing phase II study of SBRT of T1-T2N0M0 inoperable NSCLC in a dummy run oriented on volumes and doses. Six Scandinavian centres participated. Each centre received CT-scans covering the whole lung volumes of two patients with instructions to follow the study protocol when outlining tumour and target volumes, prescribing doses and creating dose plans. Volumes and doses of the 12 dose plans were evaluated according to the study protocol. For the two patients the GTV volume range was 24 to 39 cm3 and 26 to 41 cm3, respectively. The PTV volume range was 90 to 116 cm3, and 112 to 155 cm3, respectively. For all plans the margin between CTV and PTV in all directions followed in detail the protocol. The prescribed dose was for all centres 45 Gy/3 fractions (isocentre dose about 66 Gy). The mean GTV doses ranged from 63 to 67 Gy and from 63 to 68 Gy, respectively. The minimum doses for GTV were between 50–64 Gy and between 55–65 Gy, respectively. The dose distribution was conformed to PTV for 10 of 12 plans and 2 of 12 plans from one centre had sub-optimal dose distribution. Most of the volume and dose parameters for the participating centres showed fully acceptable compliance with the study protocol.

Clinical, Dosimetric, and Location-Related Factors to Predict Local Control in Non-Small Cell Lung Cancer

Clinical, Dosimetric, and Location-Related Factors to Predict Local Control in Non-Small Cell Lung Cancer

Assessing Respiration-Induced Tumor Motion and Margin of Internal Target Volume for Image-Guided Radiotherapy of Lung Cancers

Materials/Methods: A total of 72 lung cancer patients (mainly stage I–IV non-small-cell lung cancers) were included in this study to evaluate tumor motion caused by respiration. All patients underwent a single 4DCT session under quiet normal breathing during standard treatment simulation on a commercial CT scanner (GE Medical System). Breathing traces were recorded with a commercial respiratory monitoring system (RPM, Varian Oncology) and were used to reconstruct and re-sort CT images into 10 respiratory phases. Automated rigid-body based image registration was used to align the GTV of each respiratory phase to its reference template defined on the expiratory phase. 3D image deformation was applied to 4D images of 8 patients as an independent verification of the rigid-body registration. The volume and location of the GTV were also measured for each patient. The location of the GTV was defined based on the relative distance between the GTV center-of-mass and the edge of the lung along anterior/posterior (AP) and superior/inferior (SI) directions, and body center line along the lateral direction. Diaphragm motion was measured along the SI direction on the same plane as the GTV center-of-mass. The GTV motion vector and its relationship with the GTV volume, location, and diaphragm motion were analyzed statistically for all patients.

SU-FF-J-74: Tumor Motion and Tumor Shape Changes During Radiotherapy of Bladder Cancer

Purpose: First, to quantify bladder tumor motion in three dimensions. Secondly, to relate the motion to changes in bladder filling. Thirdly, to evaluate shape and volume changes of the GTV during the course of the radiotherapy. Method and Materials: CT images were obtained for 21 bladder cancer patients. Next to the planning CT scan, each patient underwent 8 to 11 follow-up CT scans. These scans were matched on the bony anatomy. Patients were instructed to empty their bladder and drink 250 cc water one hour prior to acquisition. Tumor, bladder and rectum were delineated manually. For each patient, the variation in tumor position (day-to-day tumor motion) was determined by calculating the shift of the center of gravity (CG) of each GTV relative to the mean CG. These shifts were compared with model results from a previous study, concerning patients with a healthy bladder. The correlation between bladder volume and GTV position was determined. To study GTV shape changes, we matched all GTVs and determined the residual shape errors in terms of SDs. Results: Tumor motion was largest in Cranial-Caudal and A-P direction and ranged from 0.1 to 0.9 cm. The movement was strongly correlated with the bladder filling and the tumor location on the bladder wall. The average SD of the GTV shape changes, excluding the 10% highest values, ranged from 0.1 to 0.35 cm. The SD of the GTV volume ranged from 0.5 to 13 cc and was not dependent on the GTV volume. We found no significant volume time trend. Conclusion: We demonstrated that, despite large differences in bladder filling, variations in GTV shape were small. We could not prove any GTV volume trend with time. Geometrical uncertainties of the GTV position were mainly caused by variation in bladder volume and depended strongly on the GTV location.

WE‐C‐J‐6C‐04: Image‐Guided Adaptive Therapy for Lung Cancer

Purpose: Because the GTV for many lung cancer patients decreased during the course of treatment, the margin effectively gets larger as the tumor reduces in size. This work describes the development and assessment of a technique for image‐guided adaptive radiation therapy for lung cancer. Method and Materials: Megavoltage CT (MVCT) images of the GTV were acquired daily on a helical tomotherapy system. These images were used to position the patient and to measure reduction in GTV volume. A planning study was conducted to determine the amount of lung‐sparing that could have been achieved if adaptive therapy were utilized. Treatment plans were created where the target volumes were reduced following measured tumor reduction. Results: A total of 158 MVCT imaging sessions have been performed on 7 lung patients. The GTV reduced by 60 to 80% during the course of treatment. The tumor reduction in the first 60 days of treatment can be modeled using the 2nd order polynomial R = 0.0002t 2−0.0219 t+1.0, where (R) is the percent reduction in GTV and (t) is the elapsed days. Based on these treatment‐planning studies, the absolute volume of ipsilateral lung receiving 20 Gy can be reduced between 5 and 25 percent (17% mean) by adapting the treatment delivery. The benefits of adaptive are the greatest for tumor volumes ⩾25 cm 3 and are directly dependent on the GTV reduction during treatment. Conclusion: MVCT based image‐guidance can be used to position lung cancer patients daily. This has the potential to decrease margins associated with daily setup error. Furthermore, the adaptive therapy technique described in this work can decrease the volume of healthy lung tissue receiving above 20 Gy. Conflict of Interest: Research supported by TomoTherapy, Inc.

TU-C-T-617-06: Importance of Pre-Fraction Helical CT Isocenter Verification in Extracranial Stereotactic Radiosurgery

Purpose: To quantify the impact of pre-fraction helical CT isocenter verification vs. setup based on planning CT in fractionated extracranial stereotactic radiosurgery. Method and Materials: Treatment plans (Elekta PrecisePlan) and pre-fraction isocenter verification helical CT scans for 12 patients (40 fractions) were recovered from treatment plan archives. All structures were contoured by a single physician at the time of treatment. Each plan was imported into a customizable treatment plan analysis suite (CERR). Using CERR, pre-fraction isocenter verification CT scans were fused with the original treatment plan using the external body frame as a reference. The original planned dose distribution was then translated from original treatment plan isocenter to pre-fraction verification isocenters in each fraction. Dose and volume parameters for pertinent structures were automatically extracted using both registration methods (planned or pre-fraction scans) for the original treatment plan and for all subsequent fractions. All patients were treated using the pre-fraction verified isocenter rather than pre-calculated body frame fiducials as per our institutional policies. Results: GTV volumes on pre-fraction CTs varied from original planned GTV volume (64%–203%, mean=101.8+/−26.5%) largely due to helical sampling of a mobile target. Using the external body frame as the only setup reference would have resulted in geographic misses (<80% coverage of 95% of GTV) in 7/40 (17.5%) fractions. Pre-fraction isocenter verification resulted in improved D95 GTV coverage (88–102%, mean=99.3% +/−2.4%) with no geographic misses. Conclusion: The current RTOG protocol (0236) evaluating extracranial stereotactic radiosurgery does not require pre-fraction CT tumor position verification. Our institutional policy is to verify isocenter/tumor position prior to each fraction via CT. Although helical scanning artifacts are present, pre-fraction CT-based isocenter verification may provide more consistent tumor coverage than setup to planned body frame fiducials. Conflict of Interest: Support for this research was provided in part by Elekta, Inc.

SU-FF-J-15: Evaluation of Lung Tumor Dose Coverage in Free-Breathing Treatment Plans Using Respiration-Correlated CT

Purpose: We quantify the effect of respiration on 3D conformal radiotherapy of lungtumors in terms of dosimetric end‐points using respiration‐correlated CT scans (RCCT). Method and Materials: Six patients received RCCT scans (GE Advantage4D CT). Repeat slices were obtained at each couch position and retrospectively sorted according to respiratory phase using an external respiratory monitor. We generated simulated free‐breathing (FB) CT sets by assembling slices at different respiratory phases from the RCCT study. FB treatment plans similar to the clinical plan were created based on a 1.5 cm expansion of the gross tumor volume (GTV) in one patient and 1.0 cm in two other patients. Superposition‐convolution dose calculations (ADAC/Pinnacle system) were used. We applied the FB plan to the RCCT data sets at various respiratory phases and evaluated dose coverage of the GTV and clinical target volume (CTV=GTV+6mm). Results: Initial results are presented for an extreme situation: the patient with the largest tumor motion (2.3 cm, inferior/superior direction) and the start phase of the simulated FB scan chosen to have the tumor at its most superior position. The D99% values are: 1) FB plan: GTV 5833 cGy, CTV 5706 cGy. 2) FB plan applied to end‐inspiration: GTV 5828 cGy, CTV 5433 cGy. The GTV and CTV are only modestly underdosed at end‐inspiration (tumor most inferior), in this worst case scenario (FB plan based on a tumor at a superior position). Dosimetric indices at end‐expiration show less change. Preliminary studies on two other patients with smaller tumor excursions show similarly small dosimetric changes. Conclusion:Tumor coverage by free‐breathing based plans with standard margins changes only slightly with breathing phase in an extreme case. This study examines only respiratory motion and not interfractional tumor motion or setup error which also affect tumordose coverage.

TU‐D‐J‐6C‐05: Investigation of the Actually Delivered Patient Dose in Lung IMRT Treatment Based On Deformable Registration of 4D CT Data and Monte Carlo Simulations

Purpose: To accurately calculate the difference between prescribed and delivered dose caused by respiratory motion and artifacts in free breathing helical CT (fbCT) for lung IMRT treatments, and to estimate the impact of this difference in clinical outcome. Method and Materials: Ten cases were studied. For all patients, fbCT and 4DCT reconstructed at 10 phases of the respiratory cycle were available. Patients were selected to have a wide range of tumor motion, size, and position. CORVUS was used to make two IMRT plans calculated on the fbCT for GTV (volume determined on fbCT) and ITV (volume determined by 4DCT) targets respectively. The prescribed dose was 60Gy. The fluence maps and beam setup parameters of the IMRT plans were used by the Monte Carlo dose calculation engine MCSIM for absolute dose calculation on free breathing and 4DCT data. CT deformable registration between the breathing phases was performed and the composite dose over the whole breathing cycle was calculated for the GTV, CTV and lungs. EUD and TCP/NTCP values were determined for the composite dose over the whole breathing cycle based on both plans. Results: For a patient with 4 cm peak to peak tumor movement, a planned CTV EUD of 58 Gy was reduced to 54Gy and 33Gy respectively for the composite 4D dose distribution of ITV and GTV plans. 3‐year control estimates for this patient, assuming that 3‐year local control after 60Gy in the GTV is 30%, were reduced to 29% and 23% for the ITV and the free breathing plans respectively. Conclusion: With the advent of 4DCT, CT data deformable registration and Monte Carlo dose calculations, it is feasible to accurately calculate in retrospect the actually delivered dose and compare it with what historically was assumed to be delivered.

Effect of patient setup errors on simultaneously integrated boost head and neck IMRT treatment plans

The purpose of this study is to determine dose delivery errors that could result from random and systematic setup errors for head-and-neck patients treated using the simultaneous integrated boost (SIB)-intensity-modulated radiation therapy (IMRT) technique. Twenty-four patients who participated in an intramural Phase I/II parotid-sparing IMRT dose-escalation protocol using the SIB treatment technique had their dose distributions reevaluated to assess the impact of random and systematic setup errors. The dosimetric effect of random setup error was simulated by convolving the two-dimensional fluence distribution of each beam with the random setup error probability density distribution. Random setup errors of sigma = 1, 3, and 5 mm were simulated. Systematic setup errors were simulated by randomly shifting the patient isocenter along each of the three Cartesian axes, with each shift selected from a normal distribution. Systematic setup error distributions with Sigma = 1.5 and 3.0 mm along each axis were simulated. Combined systematic and random setup errors were simulated for sigma = Sigma = 1.5 and 3.0 mm along each axis. For each dose calculation, the gross tumor volume (GTV) received by 98% of the volume (D(98)), clinical target volume (CTV) D(90), nodes D(90), cord D(2), and parotid D(50) and parotid mean dose were evaluated with respect to the plan used for treatment for the structure dose and for an effective planning target volume (PTV) with a 3-mm margin. Simultaneous integrated boost-IMRT head-and-neck treatment plans were found to be less sensitive to random setup errors than to systematic setup errors. For random-only errors, errors exceeded 3% only when the random setup error sigma exceeded 3 mm. Simulated systematic setup errors with Sigma = 1.5 mm resulted in approximately 10% of plan having more than a 3% dose error, whereas a Sigma = 3.0 mm resulted in half of the plans having more than a 3% dose error and 28% with a 5% dose error. Combined random and systematic dose errors with sigma = Sigma = 3.0 mm resulted in more than 50% of plans having at least a 3% dose error and 38% of the plans having at least a 5% dose error. Evaluation with respect to a 3-mm expanded PTV reduced the observed dose deviations greater than 5% for the sigma = Sigma = 3.0 mm simulations to 5.4% of the plans simulated. Head-and-neck SIB-IMRT dosimetric accuracy would benefit from methods to reduce patient systematic setup errors. When GTV, CTV, or nodal volumes are used for dose evaluation, plans simulated including the effects of random and systematic errors deviate substantially from the nominal plan. The use of PTVs for dose evaluation in the nominal plan improves agreement with evaluated GTV, CTV, and nodal dose values under simulated setup errors. PTV concepts should be used for SIB-IMRT head-and-neck squamous cell carcinoma patients, although the size of the margins may be less than those used with three-dimensional conformal radiation therapy.

Dosimetric and clinical results of three-dimensional conformal radiotherapy for locally recurrent nasopharyngeal carcinoma

PurposeTo assess the dosimetric and clinical results of three-dimensional conformal radiotherapy (3D CRT) for locally recurrent nasopharyngeal carcinoma (NPC). MethodsA total of 86 patients with locally recurrent NPC were retreated with 3D CRT. The median prescribed dose was 68Gy with 2Gy per fractionation. Dosimetric quality was evaluated with dose distribution in planning target volume (PTV) and specified organs at risk (OAR), dose conformity index (CI) and dose homogeneity index (HI). The actuarial rate of local failure-free (LFF), overall survival (OS) and major late toxicities (MLT) were estimated with Kaplan–Meier method. Multivariate analysis for prognosis was performed using the Cox regression proportional hazards model. ResultsThe mean dose to PTV averaged 66.8Gy, and the dose to specified OAR was acceptable. The average value of CI and HI was 0.59 and 9.1%. The 5-year actuarial rate of LFF and OS was 71 and 40%, respectively. The 5-year actuarial incidence of MLT≥Grade 3 and ≥Grade 4 were 100 and 49%, respectively. The major prognostic factors were T stage and the size of gross tumor volume (GTV). Advanced T stage and large GTV volume were associated with poor LFF and OS and high risk of MLT. ConclusionThe dosimetric quality of 3D CRT for locally recurrent NPC is generally excellent. A relatively high local control was achieved with this technique. However, the incidence of late toxicities were not found to decrease as originally expected. Early diagnosis of the recurrence and reasonable definition of the target volume are crucial to achieve a better outcome.

Quantification of shape variation of prostate and seminal vesicles during external beam radiotherapy

The prostate is known to translate and rotate under influence of rectal filling changes and many studies have addressed the magnitude of these motions. However, prostate shape variations also have been reported. For image-guided radiotherapy, it is essential to know the relative magnitude of translations, rotations, and shape variation so that the most appropriate correction strategy can be chosen. However, no quantitative analysis of shape variation has been performed. It is, therefore, the purpose of this article to develop a method to determine shape variation of complex organs and apply it to determine shape variation during external beam radiotherapy of a GTV (gross tumor volume) consisting of prostate and seminal vesicles. For this study, the data of 19 patients with prostate cancer were used. Each patient received a planning computed tomography (CT) scan and 8-12 (11 on average) repeat CT scans that were made during the course of conformal radiotherapy. One observer delineated the GTV in all scans, and volume variations were measured. After matching the GTVs for each patient for translation and rotation, a coverage probability matrix was constructed and the 50% isosurface was taken to determine the average GTV surface. Perpendicular distances between the average GTV and the individual GTVs were calculated for each point of the average GTV, and their variation was expressed in terms of local standard deviation (SD). The local SDs of the shape variation of all 19 patients were mapped onto a reference case by matching and morphing of the individual average GTVs. Repeated delineation of the GTV was done for 6 patients to determine intraobserver variation. Finally, the measured shape variation was corrected for intraobserver variation to estimate the "real" shape variation. No significant variations in GTV volume were observed. The measured shape variation (including delineation variation) was largest at the tip of the vesicles (SD = 2.0 mm), smallest at the left and right side of the prostate (SD = 1.0 mm), and average elsewhere (SD = 1.5 mm). At the left, right, and cranial sides of the prostate, the intraobserver variation was of the same order of magnitude as the measured shape variation; elsewhere it was smaller. However, the accuracy of the estimated SD for intraobserver variation was about half of the accuracy of the estimated SD for the measured shape variation, giving an overall uncertainty of maximum 0.6 mm SD in the estimate of the "real" shape variation. The "real" shape variation was small at the left, right, and cranial side of the prostate (SD <0.5 mm) and between 0.5 mm and 1.6 mm elsewhere. We developed a method to quantify shape variation of organs with a complex shape and applied it to a GTV consisting of prostate and seminal vesicles. Deformation of prostate and seminal vesicles during the course of radiotherapy is small (relative to organ motion). Therefore, it is a valid approximation in image-guided radiotherapy of prostate cancer, in first order, to correct only for setup errors and organ motion. Prostate and seminal vesicles deformation can be considered as a second-order effect.

Defining a radiotherapy target with positron emission tomography

F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging is now considered the most accurate clinical staging study for non-small-cell lung cancer (NSCLC) and is also important in the staging of multiple other malignancies. Gross tumor volume (GTV) definition for radiotherapy, however, is typically based entirely on computed tomographic data. We performed a series of phantom studies to determine an accurate and uniformly applicable method for defining a GTV with FDG-PET. A model-based method was tested by a phantom study to determine a threshold, or unique cutoff of standardized uptake value based on body weight (standardized uptake value [SUV]) for FDG-PET based GTV definition. The degree to which mean target SUV, background FDG concentration, and target volume influenced that GTV definition were evaluated. A phantom was constructed consisting of a 9.0-L cylindrical tank. Glass spheres with volumes ranging from 12.2 to 291.0 cc were suspended within the tank, with a minimum separation of 4 cm between the edges of the spheres. The sphere volumes were selected based on the range of NSCLC patient tumor volumes seen in our clinic. The tank and spheres were filled with a variety of known concentrations of FDG in several experiments and then scanned using a General Electric Advance PET scanner. In the initial experiment, six spheres with identical volumes were filled with varying concentrations of FDG (mean SUV = 1.85 approximately 9.68) and suspended within a background bath of FDG at a similar concentration to that used in clinical practice (0.144 muCi/mL). The second experiment was identical to the first, but was performed at 0.144 and 0.036 muCi/mL background concentrations to determine the effect of background FDG concentration on sphere definition. In the third experiment, six spheres with volumes of 12.2 to 291.0 cc were filled with equal concentrations of FDG and suspended in a standard background FDG concentration of 0.144 muCi/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators. There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 x (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms. An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process.

Dosimetric effect of respiratory motion in external beam radiotherapy of the lung

Background and purposeTo study the effect of breathing motion on gross tumor volume (GTV) coverage for lung tumors using dose-volume histograms and relevant dosimetric indices. Patients and methodsTreatment plans were chosen for 12 patients treated at our institution for lung carcinoma. GTV volumes of these patients ranged from 1.2 to 97.3 cm3. A margin of 1–2 cm was used to generate the planning target volume (PTV). Additional margins of 0.6–1.0 cm were added to the PTV when designing treatment portals. For the purposes of TCP calculation, the prescription dose was assumed to be 70Gy to remove the effects of prescription differences. Setup error was incorporated into the evaluation of treatment plans with a systematic component of σRL=0.2cm, σAP=0.2cm, and σSI=0.3cm and a random component of σRL=0.3cm, σAP=0.3cm, and σSI=0.3cm. Breathing motion was incorporated into these plans based on an independent analysis of fluoroscopic movies of the diaphragm for 7 patients. The systematic component of breathing motion (σRL=0.3cm, σAP=0.2cm, and σSI=0.6cm) was incorporated into the treatment plans on a slice by slice basis. The intrafractional component of breathing motion (σRL=0.3cm, σAP=0.2cm, and σSI=0.6cm) was incorporated by averaging the dose calculation over all displacements of the breathing cycle. Each patient was simulated 500 times to discern the range of possible outcomes. The simulations were repeated for a worst case scenario which used only breathing data with a large diaphragmatic excursion, both with and without intrafractional breathing motion. ResultsDose to 95% of the GTV (D95), volume of the GTV receiving 95% of the prescription dose (V95), and TCP changed an average of −1.4±4.2, −1.0±3.3, and −1.4±3.8%, respectively, with the incorporation of normal breathing effects. In the worst case scenario (heavy breathers), D95 and V95 changed an average of −9.8±10.1 and −8.3±11.3%, respectively, and TCP changed by −8.1±9.1%. GTVs with volumes greater than 60 cm3 showed stronger sensitivity to breathing especially if the shape was non-ellipsoidal. In the normal breathing case, the probability of a decrease in D95, V95, or TCP of a magnitude greater than 10% is less than 4%, and in the worse case scenario this probability is approximately 30–40% with intrafractional breathing motion included, and less than 10% with intrafractional breathing motion not included. ConclusionsWith the PTV margins routinely used at our center, the effects of normal breathing on coverage are small on the average, with a less than 4% chance of a 10% or greater decrease in D95, V95, or TCP. However, in patients with large respiration-induced motion, the effect can be significant and efforts to identify such patients are important.

Potential of intensity-modulated radiotherapy to escalate doses to head-and-neck cancers: What is the maximal dose?

Purpose To investigate the potential of intensity-modulated radiotherapy (IMRT) to escalate doses to head-and-neck cancer and find the maximal dose that could be prescribed to the target volume with IMRT while doses to critical organs were maintained at their currently acceptable levels. The secondary goal was to search for limits in current IMRT technology. Methods and materials For a group of 12 head-and-neck cancer patients with different tumor locations and shapes, we performed IMRT planning using a simultaneous integrated boost strategy, that is, the gross tumor volume (GTV), clinical target volume (CTV), and electively treated nodes were treated simultaneously at different dose levels. The critical structures involved in the treatment field that needed to be spared included the brainstem, spinal cord, and parotid glands, depending on the disease site. Nine coplanar 6-MV photon beams were used for planning with the IMRT system developed at our institution, and dose–volume criteria were used for optimization. By varying the optimization parameters, we gradually increased the dose to the GTV while keeping the dose to the critical structures at less than the acceptable tolerance level. The criteria for accepting the plan included the following: ( 1) the prescription dose to the GTV had to cover 99% of the volume, and the dose homogeneity of the GTV needed to be <10%; ( 2) the prescription to the CTV (which was set either at 60 Gy or 10 Gy less than that of the GTV) had to cover 95% of the volume, and the same amount of normal tissue outside the CTV received the CTV prescription dose as in the current acceptable plan; ( 3) the prescription to the electively treated lymph nodes needed to cover 90% of the volume; and ( 4) the maximal dose to the brainstem and spinal cord had to be <55 Gy and 45 Gy, respectively. For parotid glands, the dose needed to be as low as possible without compromising the target doses. The deliverable plans as determined by the actual multileaf collimator leaf sequences were used for the final evaluation. To verify that the acceptable plans were deliverable, the experimental measurements of planar dose distribution were performed in phantom with film. Results The maximal dose to the GTV varied from 86 to 176 Gy if the CTV dose increased with the GTV dose. It was reduced to 76–82 Gy if the CTV dose was kept at 60 Gy. The competing criteria usually are the requirements of the tolerance doses to the critical organs and target dose homogeneity, not the target prescription dose. Using more beams only increased the dose marginally. The results could change significantly if a different set of criteria for the plan evaluation were used. Dosimetric measurements confirmed that such a high dose and dose gradient could be delivered accurately with dynamic multileaf collimators. Statistical analyses showed no significant correlations between the maximal doses and the number of GTVs and volume of GTVs and CTVs. Conclusion Doses to head-and-neck cancers with simultaneous integrated boost IMRT can be escalated to a greater level than currently prescribed clinically. The limit of IMRT in head-and-neck cancer has not been reached at the current prescription level of 70 Gy. Such high total and fractionated doses should be carefully evaluated before being prescribed clinically.

Acute ocular toxicity and long-term visual outcome of primary and adjuvant hyperfractionated/accelerated radiation therapy of advanced paranasal sinus cancer employing proton irradiation

Materials/Methods: Between 1991 and 2001, HART (4 MeV photons and 160 MeV protons) was used to treat 35 pts with advanced stage primary (n 32) or recurrent (n 3) malignant tumors of the paranasal sinuses for whom full neuroophtalmologic follow-up was obtained. Median age was 52 years (range, 18.5-74.4). Ten (29%) unresectable patients were treated with primary and 25 (71%) with adjuvant radiation therapy, respectively. Chemotherapy (CT) was administered to 13 (37%) patients, however, none received concurrent CT. Prospectively specified neuro-ophtalmologic follow-up consisted of pupillary examination, exophtalmometry, color vision and ocular pressure measurements, motility testing, as well as dilated fundus exam and Goldmann visual field. The median dose to the macroscopic gross tumor volume (GTV) was 69.6 CGE (range, 60-76.6 CGE, CGE proton Gy 1.1 RBE). Optical apparatus dose constraint was 2 CGE/day and 56 CGE total dose, respectively. If clinically indicated, the treating physician had the option to relax the optical dose constraints. Median GTV and clinical tumor volume were 90 cc (range, 5.4-318) and 251 cc (range, 40.9-636), respectively. Lens and retinal late complications were graded according to objective portion of the SOMA scale of the Late Effects of Normal Tissue (LENT) Scoring system. Other late ocular/visual symptoms were classified according to the NCI Common Toxicity Criteria (CTC) grading system. Disease-free Survival (DFS) and visual complication free survival (CFS) rate were calculated using KaplanMeier method. The studied risk factors for late visual complications included dose, gender, age, acute ocular toxicity, GTV volume, adjuvant chemotherapy and follow-up length. Statistical analysis was performed on SAS 8.1 software, using adequate methods including Student T-test and Log rank analysis. The median follow-up was 37.6 months (range, 4.4-122.8).

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.

Definition of gross tumor volume in lung cancer: inter-observer variability

Background and purpose: To determine the inter-observer variation in gross tumor volume (GTV) definition in lung cancer, and its clinical relevance.Material and methods: Five clinicians involved in lung cancer were asked to define GTV on the planning CT scan of eight patients. Resulting GTVs were compared on the base of geometric volume, dimensions and extensions. Judgement of invasion of lymph node (LN) regions was evaluated using the ATS/LCSG classification of LN. Clinical relevance of the variation was studied through 3D-dosimetry of standard conformal plans: volume of critical organs (heart, lungs, esophagus, spinal cord) irradiated at toxic doses, 95% isodose volumes of GTVs, normal tissue complication probabilities (NTCP) and tumor control probabilities (TCP) were compared for evaluation of observer variability.Results: Before evaluation of observer variability, critical review of planning CT scan led to up- (two cases) and downstaging (one case) of patients as compared to the respective diagnostic scans. The defined GTVs showed an inter-observer variation with a ratio up to more than 7 between maximum and minimum geometric content. The dimensions of the primary tumor had inter-observer ranges of 4.2 (transversal), 7.9 (cranio-caudal) and 5.4 (antero-posterior) cm. Extreme extensions of the GTVs (left, right, cranial, caudal, anterior and posterior) varied with ranges of 2.8–7.3 cm due to inter-observer variation. After common review, only 63% of involved lymph node regions were delineated by the clinicians (i.e. 37% are false negative). Twenty-two percent of drawn in lymph node regions were accepted to be false positive after review. In the conformal plans, inter-observer ranges of irradiated normal tissue volume were on average 12%, with a maximum of 66%. The probability (in the population of all conformal plans) of irradiating at least 95% of the GTV with at least 95% of the nominal treatment dose decreased from 96 to 88% when swapping the matched GTV with an unmatched one. The average (over all patients) inter-observer range in NTCP varied from 5% (spinal cord) to 20% (ipsilateral lung), whereas the maximal ranges amounted 16% (spinal cord) to 45% (heart). The average TCP amounted 51% with an average range of 2% (maximally 5%) in case of matched GTVs. These values shifted to 42% (average TCP) with an average range of 14% (maximally 31%) when defining unmatched GTVs. Four groups of causes are suggested for the large inter-observer variation: (1) problems of methodology; (2) impossible differentiation between pathologic structures and tumor; or (3) between normal structures and tumor, and (4); lack of knowledge. Only the minority of these can be resolved objectively. For most of the causal factors agreements have to be made between clinicians, intra- and inter-departmentally. Some of the factors will never be unequivocally solved.Conclusions: GTV definition in lung cancer is one of the cornerstones in quality assurance of radiotherapy. The large inter-observer variation in GTV definition jeopardizes comparison between clinicians, institutes and treatments.

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 Ho's (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 Ho's treatment technique. The same patients were re-planned using a modified Ho's 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 Ho's technique.Results: The median volumes of GTV, CTV and PTV covered by the 95% isodose in Ho's 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 Ho's technique had consistently produced good local control for NPC. However, there is potential room for enhancing the local control further because after modifying Ho's 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 V95. The V95 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 Ho's 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 (Dmax) 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 Dmax of 40.8 Gy in phase I and of 4.8 Gy in phase II. After modifying Ho's technique by 3-D BEV customization of the treatment portals, the Dmax 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 Ho's 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 Ho's 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. Ho's technique can be improved by using 3-D BEV to customize the treatment portals with multileaf collimators or blocks.

Proton radiation therapy (prt) for pediatric optic pathway gliomas: comparison with 3d planned conventional photons and a standard photon technique

Purpose: Following adequate therapy, excellent long-term survival rates can be achieved for patients with optic pathway gliomas. Therefore, avoidance of treatment-related functional long-term sequelae is of utmost importance. Optimized sparing of normal tissue is of primary concern in the development of new treatment modalities. The present study compares proton radiation therapy (PRT) with a three-dimensional (3D)-planned multiport photon and a lateral beam photon technique for localized and extensive optic pathway tumors. Methods and Materials: Between February 1992 and November 1997, seven children with optic pathway gliomas underwent PRT. For this study, we computed proton, 3D photon, and lateral photon plans based on the same CT data sets, and using the same treatment planning software for all plans. Radiation exposure for normal tissue and discrete organs at risk was quantified based on dose-volume histograms. Results: Gross tumor volume (GTV) ranged from 3.9 cm 3 to 127.2 cm 3. Conformity index (relation of encompassing isodose to GTV volume) was 2.3 for protons, 2.9 for 3D photons, and 7.3 for lateral photons. The relative increase of normal tissue (NT) encompassed at several isodose levels in relation to NT encompassed by the 95% proton isodose volume was computed. Relative NT volume of proton plan isodoses at the 95%, 90%, 80%, 50%, and 25% isodose level increased from 1 to 1.6, 2.8, 6.4, to a maximum of 13.3. Relative volumes for 3D photons were 1.6, 2.4, 3.8, 11.5, and 34.8. Lateral plan relative values were 6, 8.3, 11.5, 19.2, and 26.8. Analysis for small (< 20 cm 3) and larger (> 80 cm 3) tumors showed that protons encompassed the smallest volumes of NT at all isodose levels. Comparable conformity and high-dose gradient were achieved for proton and 3D photon plans in small tumors. However, with increasing tumor volume and complexity, differences became larger. At the 50% isodose level, 3D photons were superior to lateral photons for small tumors; this advantage was equalized for larger tumors. At the lowest isodose level, 3D photons encompassed the highest amount of NT. Analysis of organs at risk showed that PRT reduced doses to the contralateral optic nerve by 47% and 77% compared to 3D photons and lateral photons, respectively. Reductions were also seen for the chiasm (11% and 16%) and pituitary gland (13% and 16%), with differences at clinically relevant tolerance levels. Furthermore, reduced dose exposure of both temporal lobes (sparing 39% and 54%) and frontal lobes was achieved with PRT. Conclusion: PRT offered a high degree of conformity to target volumes and steep dose gradients, thus leading to substantial normal tissue sparing in high- and low-dose areas. It is expected that this will result in decreased long-term toxicity in the maturing child. Advantages of proton versus 3D photon plans became increasingly apparent with increasing target size and tumor complexity. Even in small tumors, conformity of 3D photon irradiation came at the expense of a larger amount of NT receiving moderate to low radiation doses. Lateral photons resulted in inferior dose distribution with high radiation exposure of clinically relevant normal tissues.