Planning Target Volume Reduction Research Articles

Evaluation of the Planning Target Volume in the Treatment of Head and Neck Cancer With Intensity-Modulated Radiotherapy: What Is the Appropriate Expansion Margin in the Setting of Daily Image Guidance?

To compare patterns of disease failure among patients treated with intensity-modulated radiotherapy (IMRT) in conjunction with daily image-guided radiotherapy (IGRT) for head and neck cancer, according to the margins used to expand the clinical target volume (CTV) to create a planning target volume (PTV). Two-hundred and twenty-five patients were treated with IMRT for squamous cell carcinoma of the head and neck. Daily IGRT scans were acquired using either kilovoltage or megavoltage volumetric imaging prior to each delivered fraction. The first 95 patients were treated with IMRT with 5-mm CTV-to-PTV margins. The subsequent 130 patients were treated using 3-mm PTV expansion margins. Two-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 76%, 78%, and 81%, respectively. There were no differences with respect to any of these endpoints among patients treated with 5-mm and 3-mm PTV expansion margins (p > 0.05, all). The 2-year local-regional control rate for patients treated with IMRT with 5-mm and 3-mm PTV margins was 78% and 78%, respectively (p = 0.96). Spatial evaluation revealed no differences in the incidences of marginal failures among those treated with 5-mm and 3-mm PTV margins. The use of 3-mm PTV expansion margins appears adequate and did not increase local-regional failures among patients treated with IMRT for head and neck cancer. These data demonstrate the safety of PTV reduction of less than 5 mm and support current protocols recommending this approach in the setting of daily IGRT.

Potential Utility of Image-guidance to Reduce PTV Margins for Patients Treated by IMRT for Head and Neck Cancer: Evaluation of Temporal-based Protocols

Although image-guided radiotherapy (IGRT) has been proposed as a means of potentially reducing planning target volume (PTV) margins, there is limited data on how to best utilize this technology to accomplish this for head and neck cancer patients. The aim of this study was to determine the optimal PTV margins required for patients treated by IMRT for head and neck cancer using commonly employed IGRT strategies. Positional alignment data was collected from 114 patients who underwent volumetric imaging with on-board kV cone beam CT (CBCT) prior to each daily IMRT fraction, resulting in 3, 575 image data sets. Assuming zero residual error after IGRT correction, we estimated the per fraction geometric error that would have occurred in the absence of daily IGRT correction. Population error parameters were calculated according to Van Herk's formula, and margin values were subsequently calculated for PTV expansion. Eight temporal IGRT protocols were evaluated with this method: (1) No IGRT correction; (2) IGRT correction for the first fraction; (3) IGRT correction for the first three fractions; (4) IGRT for the first five fractions; (5) IGRT for the first seven fractions; (6) IGRT weekly; (7) IGRT for the first five fractions then weekly; and (8) IGRT every other day with a running mean. In the absence of any on-board correction, the mean shifts were 0.6 ±1.9 mm, 2.0 ± 6.1 mm, 5.8 ± 5.4 mm in the primary translational axes (anteroposterior, superoinferior, and right-left directions), respectively. These positional would require PTV margins of 5.9 mm, 16.9 mm, and 14.8 mm, respectively. of the 8 IGRT protocols evaluated, the optimal less-than-daily IGRT protocol requiring the lowest hypothetical margins (1.8 mm, 2.8 mm, 1.9 mm) to ensure accurate delivery in 95% of the treated fractions was protocol 8 (IGRT on alternating days with running mean). Protocol 6 (weekly IGRT) the next optimal less-than-daily protocol, with corresponding margins of 2.7 mm, 3.9 mm, and 2.8 mm, respectively. The use of IGRT can safely allow for the reduction of PTV margins in the treatment of head and neck cancer patients using IMRT. This strategy is possible even in the setting of less-than-daily IGRT. Clinical implications will be discussed.

A Gene Expression Signature Predicts Recurrence-free Survival and Overall Survival for High-risk Surgical-pathologic Head and Neck Squamous Cell Carcinomas following Post-operative Radiotherapy

Purpose/Objective(s): Although image-guided radiotherapy (IGRT) has been proposed as a means of potentially reducing planning target volume (PTV) margins, there is limited data on how to best utilize this technology to accomplish this for head and neck cancer patients. The aim of this study was to determine the optimal PTV margins required for patients treated by IMRT for head and neck cancer using commonly employed IGRT strategies.

High-Frequency Jet Ventilation for Complete Target Immobilization and Reduction of Planning Target Volume in Stereotactic High Single-Dose Irradiation of Stage I Non–Small Cell Lung Cancer and Lung Metastases

To demonstrate the feasibility of complete target immobilization by means of high-frequency jet ventilation (HFJV); and to show that the saving of planning target volume (PTV) on the stereotactic body radiation therapy (SBRT) under HFJV, compared with SBRT with respiratory motion, can be predicted with reliable accuracy by computed tomography (CT) scans at peak inspiration phase. A comparison regarding different methods for defining the PTV was carried out in 22 patients with tumors that clearly moved with respiration. A movement span of the gross tumor volume (GTV) was defined by fusing respiration-correlated CT scans. The PTV enclosed the GTV positions with a safety margin throughout the breathing cycle. To create a PTV from CT scans acquired under HFJV, the same margins were drawn around the immobilized target. In addition, peak inspiration phase CT images (PIP-CTs) were used to approximate a target immobilized by HFJV. The resulting HFJV-PTVs were between 11.6% and 45.4% smaller than the baseline values calculated as respiration-correlated CT-PTVs (median volume reduction, 25.4%). Tentative planning by means of PIP-CT PTVs predicted that in 19 of 22 patients, use of HFJV would lead to a reduction in volume of >or=20%. Using this threshold yielded a positive predictive value of 0.89, as well as a sensitivity of 0.94 and a specificity of 0.5. In all patients, SBRT under HFJV provided a reliable immobilization of the GTVs and achieved a reduction in PTVs, regardless of patient compliance. Tentative planning facilitated the selection of patients who could better undergo radiation in respiratory standstill, both with greater accuracy and lung protection.

Additional PET/CT in week 5–6 of radiotherapy for patients with stage III non-small cell lung cancer as a means of dose escalation planning?

Background and purpose Loco-regional failure after radiotherapy with total doses of 60–70 Gy for non-small cell lung cancer (NSCLC) remains a major clinical problem. Escalation of radiation dose is often limited because of exceeding normal tissue constraints. The present study was designed to test the hypothesis that a reduction in disease volume during radiotherapy detected by FDG PET/CT would facilitate radiation dose escalation, whilst remaining within normal tissue constraints. Materials and methods Ten patients with localised inoperable NSCLC were prospectively enrolled. Each received standard 3D-conformally planned radiotherapy to a dose of 66 Gy in 33 fractions over 6.5 weeks. FDG PET/CT imaging in the treatment position was performed prior to treatment and repeated following 50 or 60 Gy. CT and PET-delineated gross tumour volumes were generated and a composite created. A margin of 15 mm was added in all planes to form the planning target volume (PTV). Treatment planning was performed to compare two dose escalation strategies: 78 Gy delivered to the initial PTV with treatment in two phases (shrinking field), i.e., 66 Gy to the initial PTV with a 12 Gy-boost to the PTV after 50/60 Gy. As an alternative planning approach the maximal dose without exceeding normal tissue constraints was evaluated for each patient (individualized dose prescription). Results There was a median PTV reduction after 50/60 Gy of 20%. Delivering 78 Gy to the initial PTV could have been achieved in 4/10 patients. Of the remaining 6, delivering 78 Gy to the initial PTV would have exceeded normal tissue constraints and no benefit was seen when delivered in two phases. The results from the individualized dose prescription indicated a higher median maximal dose when treatment would be given in two phases compared to one phase resulting in a modest increase of calculated tumour control probability. Conclusions Our data suggest that despite tumour shrinkage determined by subsequent FDG PET/CT during treatment the tested adaptive targeting strategy would result only in a modest improvement in the context of dose escalation. Further studies on the optimal use of FDG PET/CT and other approaches for dose escalation in loco-regionally advanced NSCLC are warranted.

Conventionally-fractionated image-guided intensity modulated radiotherapy (IG-IMRT): a safe and effective treatment for cancer spinal metastasis

BackgroundTreatments for cancer spinal metastasis were always palliative. This study was conducted to investigate the safety and effectiveness of IG-IMRT for these patients.Methods10 metastatic lesions were treated with conventionally-fractionated IG-IMRT. Daily kilovoltage cone-beam computed tomography (kV-CBCT) scan was applied to ensure accurate positioning. Plans were evaluated by the dose-volume histogram (DVH) analysis.ResultsBefore set-up correction, the positioning errors in the left-right (LR), superior-inferior (SI) and anterior-posterior (AP) axes were 0.3 ± 3.2, 0.4 ± 4.5 and -0.2 ± 3.9 mm, respectively. After repositioning, those errors were 0.1 ± 0.7, 0 ± 0.8 and 0 ± 0.7 mm, respectively. The systematic/random uncertainties ranged 1.4–2.3/3.0–4.1 before and 0.1–0.2/0.7–0.8 mm after online set-up correction. In the original IMRT plans, the average dose of the planning target volume (PTV) was 61.9 Gy, with the spinal cord dose less than 49 Gy. Compared to the simulated PTVs based on the pre-correction CBCT, the average volume reduction of PTVs was 42.3% after online correction. Also, organ at risk (OAR) all benefited from CBCT-based set-up correction and had significant dose reduction with IGRT technique. Clinically, most patients had prompt pain relief within one month of treatment. There was no radiation-induced toxicity detected clinically during a median follow-up of 15.6 months.ConclusionIG-IMRT provides a new approach to treat cancer spinal metastasis. The precise positioning ensures the implementation of optimal IMRT plan, satisfying both the dose escalation of tumor targets and the radiation tolerance of spinal cord. It might benefit the cancer patient with spinal metastasis.

Invasive lobular cancer and re-do surgery – extent of the problem!

Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. All patients were prescribed a dose of 45 Gy in 20 fractions to the breast with an SIB of 56 Gy in 20 fractions to the tumor bed and normalized so that D98% > 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D98% > 95% and D2% < 107%. Static tomotherapy offered significantly improved (p = 0.006) dose homogeneity to the PTVboost eval (0.079 ± 0.011) and breast minus the SIB volume (BreastSIB) (p < 0.001, 0.15 ± 0.03) compared with the PTVboost eval (0.085 ± 0.008, 0.088 ± 0.12) and BreastSIB (0.22 ± 0.05, 0.23 ± 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p < 0.001) in doses to the ipsilateral lung mean dose of 6.79 ± 2.11 Gy compared with 7.75 ± 2.54 Gy and 8.29 ± 2.76 Gy for IMRT and 3D-CRT, respectively, and significantly (p < 0.001) reduced heart doses (mean = 2.83 ± 1.26 Gy) compared to both IMRT and 3D-CRT (mean = 3.70 ± 1.44 Gy and 3.91 ± 1.58 Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to 3D-CRT in both PTV dose conformity and reduction of mean doses to the ipsilateral lung.

The Effect of Changing Technique, Dose, and PTV Margin on Therapeutic Ratio During Prostate Radiotherapy

To quantify the dosimetric and radiobiological changes seen when using intensity-modulated radiation therapy (IMRT) or planning target volume (PTV) margin reduction with consistent planning parameters in a representative sample of localized prostate cancer patients. Twenty patients were randomly selected from a cohort that received 79.8 Gy using six-field conformal radiotherapy. Using the clinical contours, PTV margin, planning system, and dose constraints, five-field IMRT plans were generated for 79.8, 83.8, and 88.0 Gy. The 88.0-Gy IMRT plan was then reoptimized with a PTV margin reduced to 3 mm. These plans were then compared using various dosimetric and radiobiological endpoints calculated for various alpha/beta. Intensity-modulated RT resulted in greater conformity to the PTV (p < 0.001). No improvement in mean normal tissue complication probabilities in the rectal wall (NTCPrw) was seen, and the modified therapeutic ratio (TR(mod)) was largely unchanged between six-field conformal and IMRT for the majority of the patients. When IMRT was used to escalate dose, NTCPrw increased by 9% at each 5% prescription increase (p < 0.001). Reducing the posterior PTV margin from 7 mm to 3 mm for an IMRT plan reduced the mean NTCPrw by 12% (p < 0.001) and resulted in a trend toward increased TR(mod)(p = 0.005). Changes in TR(mod) between conformal and IMRT planning or PTV reduction showed large interpatient variability. Changing from conformal to IMRT, or from PTV(10-7) to PTV(3), did not produce a uniform interpatient increase in TR(mod)when the CTV contained the prostate alone. Radiobiological benefits of these two methods seem to be dependent on the particular anatomy of individual patients, supporting the use of patient-specific margin, planning, and dose prescription strategies.

Dosimetric Advantages of Four-Dimensional Adaptive Image-Guided Radiotherapy for Lung Tumors Using Online Cone-Beam Computed Tomography

This study compares multiple planning techniques designed to improve accuracy while allowing reduced planning target volume (PTV) margins though image-guided radiotherapy (IGRT) with four-dimensional (4D) cone-beam computed tomography (CBCT). Free-breathing planning and 4D-CBCT scans were obtained in 8 patients with lung tumors. Four plans were generated for each patient: 3D-conformal, 4D-union, 4D-offline adaptive with a single correction (offline ART), and 4D-online adaptive with daily correction (online ART). For the 4D-union plan, the union of gross tumor volumes from all phases of the 4D-CBCT was created with a 5-mm expansion applied for setup uncertainty. For offline and online ART, the gross tumor volume was delineated at the mean position of tumor motion from the 4D-CBCT. The PTV margins were calculated from the random components of tumor motion and setup uncertainty. Adaptive IGRT techniques provided better PTV coverage with less irradiated normal tissues. Compared with 3D plans, mean relative decreases in PTV volumes were 15%, 39%, and 44% using 4D-union, offline ART, and online ART planning techniques, respectively. This resulted in mean lung volume receiving > or = 20Gy (V20) relative decreases of 21%, 23%, and 31% and mean lung dose relative decreases of 16%, 26%, and 31% for the 4D-union, 4D-offline ART, and 4D-online ART, respectively. Adaptive IGRT using CBCT is feasible for the treatment of patients with lung tumors and significantly decreases PTV volume and dose to normal tissues, allowing for the possibility of dose escalation. All analyzed 4D planning strategies resulted in improvements over 3D plans, with 4D-online ART appearing optimal.

Adaptive Radiotherapy for Prostate Cancer Using Kilovoltage Cone-Beam Computed Tomography: First Clinical Results

To evaluate the first clinical results of an off-line adaptive radiotherapy (ART) protocol for prostate cancer using kilovoltage cone-beam computed tomography (CBCT) in combination with a diet and mild laxatives. Twenty-three patients began treatment with a planning target volume (PTV) margin of 10 mm. The CBCT scans acquired during the first six fractions were used to generate an average prostate clinical target volume (AV-CTV), and average rectum (AV-Rect). Using these structures, a new treatment plan was generated with a 7-mm PTV margin. Weekly CBCT scans were used to monitor the CTV coverage. A diet and mild laxatives were introduced to improve image quality and reduce prostate motion. Twenty patients were treated with conform ART protocol. For these patients, 91% of the CBCT scans could be used to calculate the AV-CTV and AV-Rect. In 96% of the follow-up CBCT scans, the CTV was located within the average PTV. In the remaining 4%, the prostate extended the PTV by a maximum of 1 mm. Systematic and random errors for organ motion were reduced by a factor of two compared with historical data without diet and laxatives. An average PTV reduction of 29% was achieved. The volume of the AV-Rect that received >65 Gy was reduced by 19%. The mean dose to the anal wall was reduced on average by 4.8 Gy. We safely reduced the high-dose region by 29%. The reduction in irradiated volume led to a significant reduction in the dose to the rectum. The diet and laxatives improved the image quality and tended to reduce prostate motion.

An Adaptive Off-Line Procedure for Radiotherapy of Prostate Cancer

To determine the planning target volume (PTV) margin for an adaptive radiotherapy procedure that uses five computed tomography (CT) scans to calculate an average prostate position and rectum shape. To evaluate alternative methods to determine an average rectum based on a single delineation. Repeat CT scans (8-13) of 19 patients were used. The contoured prostates of the first four scans were matched on the planning CT (pCT) prostate contours. With the resulting translations and rotations the average prostate position was determined. An average rectum was obtained by either averaging the coordinates of corresponding points on the rectal walls or by selecting the "best" rectum or transforming the pCT rectum. Dose distributions were calculated for various expanded average prostates. The remaining CT scans were used to determine the dose received by prostate and rectum during treatment. For the prostate of the pCT scan and a 10-mm margin, all patients received more than 95% of the prescribed dose to 95% of the prostate. For the average prostate, a margin of 7 mm was needed to obtain a similar result (average PTV reduction 30%). The average rectum overestimated the mean dose to the rectum by 0.4 +/- 1.6 Gy, which was better than the pCT rectum (2.1 +/- 3.0 Gy) and the alternative average rectums (1.0 +/- 2.6 Gy and 1.4 +/- 3.2 Gy). Our adaptive procedure allows for reduction of the PTV margin to 7 mm without decreasing prostate coverage during treatment. For accurate estimation of the rectum dose, rectums need to be delineated and averaged over multiple scans.

Dispositifs de repositionnement prostatique sous l'accélérateur linéaire

The development of sophisticated conformal radiation therapy techniques for prostate cancer, such as intensity-modulated radiotherapy, implies precise and accurate targeting. Inter- and intrafraction prostate motion can be significant and should be characterized, unless the target volume may occasionally be missed. Indeed, bony landmark-based portal imaging does not provide the positional information for soft-tissue targets (prostate and seminal vesicles) or critical organs (rectum and bladder). In this article, we describe various prostate localization systems used before or during the fraction: rectal balloon, intraprostatic fiducials, ultrasound-based localization, integrated CT/linear accelerator system, megavoltage or kilovoltage cone-beam CT, Calypso 4D localization system tomotherapy, Cyberknife and Exactrac X-Ray 6D. The clinical benefit in using such prostate localization tools is not proven by randomized studies and the feasibility has just been established for some of these techniques. Nevertheless, these systems should improve local control by a more accurate delivery of an increased prescribed dose in a reduced planning target volume.

Localizing moving targets and organs using motion-managed CTs

Respiration-induced target and organ motion impacts the radiotherapy strategies of some cancers. Various methods and techniques have been used to investigate motion-related radiotherapy issues, including retrospective 4-dimensional (4D) computed tomography (CT), prospective gated CT, and breath-hold CT scans. This paper reviews these methods and, particularly, the method using retrospective 4D CT scans, which has been developed at our institution. Some motion studies based on retrospective 4D CT images of patients are also examined. These studies have led to reduced planning target volume (PTV) margins for a number of patients, because the respiratory motion was observed to be minimal or gated radiotherapy was used. Respiratory motion managed CTs and, particularly, retrospective 4D CTs are proving to be useful for measuring soft tissue motion, identifying patients who could benefit from gated radiotherapy, and evaluating the effects of respiratory motion during radiotherapy.

The impact of 18 FDG-PET on target and critical organs in CT-based treatment planning of patients with poorly defined non-small-cell lung carcinoma: a prospective study

Purpose : To prospectively study the impact of coregistering 18F-fluoro-deoxy-2-glucose hybrid positron emission tomographic (FDG-PET) images with CT images on the planning target volume (PTV), target coverage, and critical organ dose in radiation therapy planning of non-small-cell lung carcinoma. Methods and Materials : Thirty patients with poorly defined tumors on CT, referred for radical radiation therapy, underwent both FDG-PET and CT simulation procedures on the same day, in radiation treatment position. Image sets were coregistered using external fiducial markers. Three radiation oncologists independently defined the gross tumor volumes, using first CT data alone and then coregistered CT and FDG-PET data. Standard margins were applied to each gross tumor volume to generate a PTV, and standardized treatment plans were designed and calculated for each PTV. Dose-volume histograms were used to evaluate the relative effect of FDG information on target coverage and on normal tissue dose. Results : In 7 of 30 (23%) cases, FDG-PET information changed management strategy from radical to palliative. In 5 of the remaining 23 (22%) cases, new FDG-avid nodes were found within 5 cm of the primary tumor and were included in the PTV. The PTV defined using coregistered CT and FDG-PET would have been poorly covered by the CT-based treatment plan in 17–29% of cases, depending on the physician, implying a geographic miss had only CT information been available. The effect of FDG-PET on target definition varied with the physician, leading to a reduction in PTV in 24–70% of cases and an increase in 30–76% of cases. The relative change in PTV ranged from 0.40 to 1.86. On average, FDG-PET information led to a reduction in spinal cord dose but not in total lung dose, although large differences in dose to the lung were seen for a few individuals. Conclusion : The coregistration of planning CT and FDG-PET images made significant alterations to patient management and to the PTV. Ultimately, changes to the PTV resulted in changes to the radiation treatment plans for the majority of cases. Where possible, we would recommend that FDG-PET data be integrated into treatment planning of non-small-cell lung carcinoma, particularly for three-dimensional conformal techniques.

Radiotherapy treatment planning for patients with non-small cell lung cancer using positron emission tomography (PET)

Purpose: Many patients with non-small cell lung cancer (NSCLC) receive external beam radiation therapy as part of their treatment. Three-dimensional conformal radiation therapy (3DCRT) commonly uses computed tomography (CT) to accurately delineate the target lesion and normal tissues. Clinical studies, however, indicate that positron emission tomography (PET) has higher sensitivity than CT in detecting and staging of mediastinal metastases. Imaging with fluoro-2-deoxyglucose (FDG) PET in conjunction with CT, therefore, can improve the accuracy of lesion definition. In this pilot study, we investigated the potential benefits of incorporating PET data into the conventional treatment planning of NSCLC. Case-by-case, we prospectively analyzed planning target volume (PTV) and lung toxicity changes for a cohort of patients.Materials and methods: We have included 11 patients in this study. They were immobilized in the treatment position and CT simulation was performed. Following CT simulation, PET scanning was performed in the treatment position using the same body cast that was produced for CT simulation and treatment. The PTV, along with the gross target volume (GTV) and normal organs, was first delineated using the CT data set. The CT and PET transmission images were then registered in the treatment planning system using either manual or automated methods, leading to consequent registration of the CT and emission images. The PTV was then modified using the registered PET emission images. The modified PTV is seen simultaneously on both CT and PET images, allowing the physician to define the PTV utilizing the information from both data sets. Dose–volume histograms (DVHs) for lesion and normal organs were generated using both CT-based and PET+CT-based treatment plans.Results: For all patients, there was a change in PTV outline based on CT images versus CT/PET fused images. In seven out of 11 cases, we found an increase in PTV volume (average increase of 19%) to incorporate distant nodal disease. Among these patients, the highest normal-tissue complication probability (NTCP) for lung was 22% with combined PET/CT plan and 21% with CT-only plan. In other four patients PTV was decreased an average of 18%. The reduction of PTV in two of these patients was due to excluding atelectasis and trimming the target volume to avoid delivering higher radiation doses to nearby spinal cord or heart.Conclusions: The incorporation of PET data improves definition of the primary lesion by including positive lymph nodes into the PTV. Thus, the PET data reduces the likelihood of geographic misses and hopefully improves the chance of achieving local control.