Wolfgang A. Tomé

Stereotactic body radiation therapy: The report of AAPM Task Group 101

Task Group 101 of the AAPM has prepared this report for medical physicists, clinicians, and therapists in order to outline the best practice guidelines for the external-beam radiation therapy technique referred to as stereotactic body radiation therapy (SBRT). The task group report includes a review of the literature to identify reported clinical findings and expected outcomes for this treatment modality. Information is provided for establishing a SBRT program, including protocols, equipment, resources, and QA procedures. Additionally, suggestions for developing consistent documentation for prescribing, reporting, and recording SBRT treatment delivery is provided.

Image guidance for precise conformal radiotherapy

PURPOSE To review the state of the art in image-guided precision conformal radiotherapy and to describe how helical tomotherapy compares with the image-guided practices being developed for conventional radiotherapy. MATERIALS AND METHODS Image guidance is beginning to be the fundamental basis for radiotherapy planning, delivery, and verification. Radiotherapy planning requires more precision in the extension and localization of disease. When greater precision is not possible, conformal avoidance methodology may be indicated whereby the margin of disease extension is generous, except where sensitive normal tissues exist. Radiotherapy delivery requires better precision in the definition of treatment volume, on a daily basis if necessary. Helical tomotherapy has been designed to use CT imaging technology to plan, deliver, and verify that the delivery has been carried out as planned. The image-guided processes of helical tomotherapy that enable this goal are described. RESULTS Examples of the results of helical tomotherapy processes for image-guided intensity-modulated radiotherapy are presented. These processes include megavoltage CT acquisition, automated segmentation of CT images, dose reconstruction using the CT image set, deformable registration of CT images, and reoptimization. CONCLUSIONS Image-guided precision conformal radiotherapy can be used as a tool to treat the tumor yet spare critical structures. Helical tomotherapy has been designed from the ground up as an integrated image-guided intensity-modulated radiotherapy system and allows new verification processes based on megavoltage CT images to be implemented.

Preservation of Memory With Conformal Avoidance of the Hippocampal Neural Stem-Cell Compartment During Whole-Brain Radiotherapy for Brain Metastases (RTOG 0933): A Phase II Multi-Institutional Trial

PURPOSE Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. PATIENTS AND METHODS Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ≤ 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with α = 0.05. RESULTS Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. CONCLUSION Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

Hippocampal-Sparing Whole-Brain Radiotherapy: A “How-To” Technique Using Helical Tomotherapy and Linear Accelerator–Based Intensity-Modulated Radiotherapy

PURPOSE Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. METHODS AND MATERIALS Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. RESULTS On average, the hippocampal avoidance volume was 3.3 cm(3), occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy(2) using helical tomotherapy and by 81% to 0.73 Gy(2) using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. CONCLUSION Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

Hippocampal Dosimetry Predicts Neurocognitive Function Impairment After Fractionated Stereotactic Radiotherapy for Benign or Low-Grade Adult Brain Tumors

PURPOSE To prospectively evaluate the association between hippocampal dose and long-term neurocognitive function (NCF) impairment for benign or low-grade adult brain tumors treated with fractionated stereotactic radiotherapy (FSRT). METHODS AND MATERIALS Adult patients with benign or low-grade adult brain tumors were treated with FSRT per institutional practice. No attempt was made to spare the hippocampus. NCF testing was conducted at baseline and 18 months follow-up, on a prospective clinical trial. Regression-based standardized z scores were calculated by using similar healthy control individuals evaluated at the same test-retest interval. NCF impairment was defined as a z score ≤-1.5. After delineation of the bilateral hippocampi according to the Radiation Therapy Oncology Group contouring atlas, dose-volume histograms were generated for the left and right hippocampi and for the composite pair. Biologically equivalent doses in 2-Gy fractions (EQD(2)) assuming an α/β ratio of 2 Gy were computed. Fishers exact test and binary logistic regression were used for univariate and multivariate analyses, respectively. Dose-response data were fit to a nonlinear model. RESULTS Of 29 patients enrolled in this trial, 18 completed both baseline and 18-month NCF testing. An EQD(2) to 40% of the bilateral hippocampi >7.3 Gy was associated with impairment in Wechsler Memory Scale-III Word List (WMS-WL) delayed recall (odds ratio [OR] 19.3; p = 0.043). The association between WMS-WL delayed recall and EQD(2) to 100% of the bilateral hippocampi >0.0 Gy trended to significance (OR 14.8; p = 0.068). CONCLUSION EQD(2) to 40% of the bilateral hippocampi greater than 7.3 Gy is associated with long-term impairment in list-learning delayed recall after FSRT for benign or low-grade adult brain tumors. Given that modern intensity-modulated radiotherapy techniques can reduce the dose to the bilateral hippocampi below this dosimetric threshold, patients should be enrolled in ongoing prospective trials of hippocampal sparing during cranial irradiation to confirm these preliminary results.

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

BACKGROUND AND PURPOSE RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5mm margin). MATERIALS/METHODS Patients with < or = 10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p<0.05 for statistical significance. RESULTS 1133 metastases were identified in 371 patients. Metastases within 5mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7-11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm(3) increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p=0.003) for the presence of perihippocampal metastasis. CONCLUSION With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.

Dosimetric comparison of left-sided whole breast irradiation with 3DCRT, forward-planned IMRT, inverse-planned IMRT, helical tomotherapy, and topotherapy

BACKGROUND AND PURPOSE To compare left-sided whole breast conventional and intensity-modulated radiotherapy (IMRT) treatment planning techniques. MATERIALS AND METHODS Treatment plans were created for 10 consecutive patients. Three-dimensional conformal radiotherapy (3DCRT), forward-planned IMRT (for-IMRT), and inverse-planned IMRT (inv-IMRT) used two tangent beams. For-IMRT utilized up to four segments per beam. For helical tomotherapy (HT) plans, beamlet entrance and/or exit to critical structures was blocked. Topotherapy plans, which used static gantry angles with simultaneous couch translation and inverse-planned intensity modulation, used two tangent beams. Plans were normalized to 50Gy to 95% of the retracted PTV. RESULTS Target max doses were reduced with for-IMRT compared to 3DCRT, which were further reduced with HT, topotherapy, and inv-IMRT. HT resulted in lowest heart and ipsilateral lung max doses, but had higher mean doses. Inv-IMRT and topotherapy reduced ipsilateral lung mean and max doses compared to 3DCRT and for-IMRT. CONCLUSIONS All modalities evaluated provide adequate coverage of the intact breast. HT, topotherapy, and inv-IMRT can reduce high doses to the target and normal tissues, although HT results in increased low doses to large volume of normal tissue. For-IMRT improves target homogeneity compared with 3DCRT, but to a lesser degree than the inverse-planned modalities.

Rectal dose sparing with a balloon catheter and ultrasound localization in conformal radiation therapy for prostate cancer

BACKGROUND AND PURPOSE To compare the rectal wall and bladder volume in the high dose region with or without the use of a balloon catheter with both three-dimensional (3D)-conformal and intensity modulated radiation therapy (CRT, IMRT) approaches in the treatment of prostate cancer. MATERIAL AND METHODS Five patients with a wide range of prostate volumes and treated with primary external beam radiation therapy for localized prostate cancer were selected for analysis. Pinnacle treatment plans were generated utilizing a 3D conformal six-field design and an IMRT seven coplanar-field plan with a novel, three-step optimization and with ultrasound localization. Separate plans were devised with a rectal balloon deflated or air inflated with and without inclusion of the seminal vesicles (SV) in the target volume. The prescription dose was 76Gy in 38 fractions of 2Gy each. Cumulative dose-volume histograms (DVHs) were analyzed for the planning target volume (PTV), rectal wall, and bladder with an inflated (60cc air) or deflated balloon with and without SV included. The volumes of rectal wall and bladder above 60, 65, and 70Gy with each treatment approach were evaluated. RESULTS Daily balloon placement was well-tolerated with good patient positional reproducibility. Inflation of the rectal balloon in all cases resulted in a significant decrease in the absolute volume of rectal wall receiving greater than 60, 65, or 70Gy. The rectal sparing ratio (RSR), consisting of a structures high dose volume with the catheter inflated, divided by the volume with the catheter deflated, was calculated for each patient with and without seminal vesicle inclusion for 3D-CRT and IMRT. For 3D-CRT, RSRs with SV included were 0.59, 0.59, and 0.56 and with SV excluded were 0.60, 0.58, and 0.54 at doses of greater than 60, 65, and 70Gy, respectively. Similarly, for IMRT, the mean RSRs were 0.59, 0.59, and 0.63 including SV and 0.71, 0.66, and 0.67 excluding SV at these same dose levels, respectively. Averaged over all conditions, inflation of the rectal balloon resulted in a significant reduction in rectal volume receiving > or =65Gy to a mean ratio of 0.61 (P=0.01) or, in other words, a mean fractional high dose rectal sparing of 39%. There was a slight overall increase to 1.13 in the relative volume of bladder receiving at least 65Gy; however, this was not significant (P=0.6). Use of an endorectal balloon with a non-image-guided 3D-CRT plan produced about as much rectal dose sparing as a highly conformal, image-guided IMRT approach without a balloon. However, inclusion of a balloon with IMRT produced further rectal sparing still. CONCLUSION These results indicate that use of a rectal balloon with a 3D-CRT plan incorporating typical treatment margins will produce significant high dose rectal sparing that is comparable to that achieved by a highly conformal IMRT with ultrasound localization. Further sparing is achieved with the inclusion of a balloon catheter in an IMRT plan. Thus, in addition to a previously reported advantage of prostate immobilization, the use of a rectal displacement balloon during daily treatment results in high dose rectal wall sparing during both modestly and highly conformal radiotherapy. Such sparing could assist in controlling and limiting rectal toxicity during increasingly aggressive dose escalation.

Selective boosting of tumor subvolumes

PURPOSE AND BACKGROUND It is no longer considered mandatory to deliver a uniform dose to the tumor volume in radiotherapy. Non-uniform doses are unavoidable in brachytherapy and in stereotactic radiosurgery, with often good results. Deliberately non-uniform doses may increase tumor control probability (TCP) and enable steeper dose gradients outside the treated volume to be achieved. New methods of tumor imaging might show regions of specific activity or hypoxia which could be selectively targeted. This paper investigates by modeling the effect of boosting, by dose ratios up to 2, for a range of tumor subvolumes. METHODS AND MATERIALS A standard linear-quadratic algorithm was used to define the dose-response curve for tumors of various volumes (numbers of clonogenic cells), radiosensitivity (SF(2)), assumed slope (gamma(50)) and dose for 50% tumor control (TCD(50)). Curves of tumor control probability (TCP) were constructed to show the increase of TCP, as a function of the ratio of boost dose to the TCD(50), above the baseline 50% TCP, for a set of different proportions of tumor volume boosted. RESULTS Calculated values of TCP increased rapidly with both boost dose ratio and with proportion of volume boosted. The increase in TCP reached a plateau after boost dose ratios of 1.2-1.3, as has been noted before, except where very large proportions of tumor volume exceeding 90% were boosted. Quite large increases of TCP, to about 75%, could be achieved if the gamma(50) slope was steep, and especially in small tumors (having fewer cells). Radiosensitivity was not an independent factor because radiosensitive tumors had a low TCD(50) and this was the baseline dose considered as unity. CONCLUSION There were few situations where a boost dose ratio exceeding 1.3 appeared to be worthwhile or necessary. Significant increases of TCP, up from 50% to 75%, might therefore be achieved for a small increase in risk of necrosis, where a substantial proportion of tumor volume (60-80%) could be boosted.

Reduction in radiation dose to lung and other normal tissues using helical tomotherapy to treat lung cancer, in comparison to conventional field arrangements.

The purpose of this study was to determine whether the use of tomotherapy in the treatment of non–small-cell lung cancer (NSCLC) has the potential to reduce radiation dose to normal tissues, in particular, the lungs, esophagus, and spinal cord, as compared with standard radiotherapy. Five patients with anatomically or physiologically inoperable stage III NSCLC were studied, representing a variety of tumor sizes and locations. For each patient, two treatment plans were generated. One was developed using conventional field arrangements (CFA), and the other for tomotherapy. Using dose–volume histogram reduction techniques, including mean normalized dose (NTDmean), V20, and effective uniform dose (EUD), the normal tissue doses for CFA and tomotherapy plans for a given fixed tumor dose were compared. In addition, the maximum tumor doses possible for a given level of mean normalized lung dose were computed and compared for the CFA and tomotherapy plans. The gross tumor volumes in the five patients studied ranged from 13.5 to 87.1 cm3. The tumor dose distributions, determined by EUD and minimum dose, were similar for both CFA and tomotherapy plans, as intended. In all cases, the NTDmean of both lungs was significantly reduced using tomotherapy planning (range: 10–53% reduction, mean: 31%). The volume of lung receiving more than 20 Gy was also reduced in all cases using tomotherapy (range: 17–37% reduction, mean: 22%). For a constant lung NTDmean, it is shown that it should be possible to increase tumor dose to up to 160 Gy in certain patients with tomotherapy. The dose to the spinal cord and esophagus was also reduced in all cases with tomotherapy planning, compared with plans generated using conventional field arrangements. Both tomotherapy, and to a lesser extent conventional three-dimensional conformal radiotherapy, have the potential to significantly decrease radiation dose to lung and other normal structures in the treatment of NSCLC. This has important implications for dose escalation strategies in the future.