Michael C. Schell

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.

Permanent prostate seed implant brachytherapy: report of the American Association of Physicists in Medicine Task Group No. 64.

There is now considerable evidence to suggest that technical innovations, 3D image-based planning, template guidance, computerized dosimetry analysis and improved quality assurance practice have converged in synergy in modern prostate brachytherapy, which promise to lead to increased tumor control and decreased toxicity. A substantial part of the medical physicists contribution to this multi-disciplinary modality has a direct impact on the factors that may singly or jointly determine the treatment outcome. It is therefore of paramount importance for the medical physics community to establish a uniform standard of practice for prostate brachytherapy physics, so that the therapeutic potential of the modality can be maximally and consistently realized in the wider healthcare community. A recent survey in the U.S. for prostate brachytherapy revealed alarming variance in the pattern of practice in physics and dosimetry, particularly in regard to dose calculation, seed assay and time/method of postimplant imaging. Because of the large number of start-up programs at this time, it is essential that the roles and responsibilities of the medical physicist be clearly defined, consistent with the pivotal nature of the clinical physics component in assuring the ultimate success of prostate brachytherapy. It was against this background that the Radiation Therapy Committee of the American Association of Physicists in Medicine formed Task Group No. 64, which was charged (1) to review the current techniques in prostate seed implant brachytherapy, (2) to summarize the present knowledge in treatment planning, dose specification and reporting, (3) to recommend practical guidelines for the clinical medical physicist, and (4) to identify issues for future investigation.

Intravascular brachytherapy physics: Report of the AAPM Radiation Therapy Committee Task Group No. 60

Recent preclinical and clinical studies indicate that irradiation using ionizing radiation in the dose range of 15 to 30 Gy may reduce the occurrence of restenosis in patients who have undergone an angioplasty. Several delivery systems of intravascular brachytherapy have been developed to deliver radiation doses in this range with minimal normal tissue toxicity. In late 1995 the American Association of Physicists in Medicine (AAPM) formed a task group to investigate these issues and to report the current state of the art of intravascular brachytherapy physics. The report of this task group is presented here.

A Prospective Pilot Study of Curative-intent Stereotactic Body Radiation Therapy in Patients With 5 or Fewer Oligometastatic Lesions

It is hypothesized that oligometastatic disease represents a state of potentially curable, limited metastases. Stereotactic body radiation therapy (SBRT) is an option for patients who are not amenable to or do not want resection.

Five year results of linac radiosurgery for arteriovenous malformations: outcome for large AVMS

PURPOSE For radiosurgery of large arteriovenous malformations (AVMs), the optimal relationship of dose and volume to obliteration, complications, and hemorrhage is not well defined. Multivariate analysis was performed to assess the relationship of multiple AVM and treatment factors to the outcome of AVMs significantly larger than previously reported in the literature. METHODS AND MATERIALS 73 patients with intracranial AVMs underwent LINAC radiosurgery. Over 50% of the AVMs were larger than 3 cm in diameter and the median and mean treatment volumes were 8.4 cc and 15.3 cc, respectively (range 0.4-143.4 cc). Minimum AVM treatment doses varied between 1000-2200 cGy (median: 1600 cGy). RESULTS The obliteration rates for treatment volumes < 4 cc, 4-13.9 cc, and > or = 14 cc were 67%, 58%, and 23%, respectively. AVM obliteration was significantly associated with higher minimum treatment dose and negatively associated with a history of prior embolization with particulate materials. No AVM receiving < 1400 cGy was obliterated. The incidence of post-radiosurgical imaging abnormalities and clinical complications rose with increasing treatment volume. For treatment volumes > 14 cc receiving > or = 1600 cGy, the incidence of post-radiosurgical MRI T2 abnormalities was 72% and the incidence of radiation necrosis requiring resection was 22%. The rate of post-radiosurgical hemorrhage was 2.7% per person-year for AVMs with treatment volumes < 14 cc and 7.5% per person-year for AVMs > or = 14 cc. CONCLUSION As AVM size increases, the dose-volume range for the optimal balance between successful obliteration and the risk of complications and post-radiosurgical hemorrhage narrows.

A Phase 3 Trial of Whole Brain Radiation Therapy and Stereotactic Radiosurgery Alone Versus WBRT and SRS With Temozolomide or Erlotinib for Non-Small Cell Lung Cancer and 1 to 3 Brain Metastases: Radiation Therapy Oncology Group 0320.

BACKGROUND A phase 3 Radiation Therapy Oncology Group (RTOG) study subset analysis demonstrated improved overall survival (OS) with the addition of stereotactic radiosurgery (SRS) to whole brain radiation therapy (WBRT) in non-small cell lung cancer (NSCLC) patients with 1 to 3 brain metastases. Because temozolomide (TMZ) and erlotinib (ETN) cross the blood-brain barrier and have documented activity in NSCLC, a phase 3 study was designed to test whether these drugs would improve the OS associated with WBRT + SRS. METHODS AND MATERIALS NSCLC patients with 1 to 3 brain metastases were randomized to receive WBRT (2.5 Gy × 15 to 37.5 Gy) and SRS alone, versus WBRT + SRS + TMZ (75 mg/m(2)/day × 21 days) or ETN (150 mg/day). ETN (150 mg/day) or TMZ (150-200 mg/m(2)/day × 5 days/month) could be continued for as long as 6 months after WBRT + SRS. The primary endpoint was OS. RESULTS After 126 patients were enrolled, the study closed because of accrual limitations. The median survival times (MST) for WBRT + SRS, WBRT + SRS + TMZ, and WBRT + SRS + ETN were qualitatively different (13.4, 6.3, and 6.1 months, respectively), although the differences were not statistically significant. Time to central nervous system progression and performance status at 6 months were better in the WBRT + SRS arm. Grade 3 to 5 toxicity was 11%, 41%, and 49% in arms 1, 2, and 3, respectively (P<.001). CONCLUSION The addition of TMZ or ETN to WBRT + SRS in NSCLC patients with 1 to 3 brain metastases did not improve survival and possibly had a deleterious effect. Because the analysis is underpowered, these data suggest but do not prove that increased toxicity was the cause of inferior survival in the drug arms.

Stereotactic Body Radiation Therapy (SBRT) for lung metastases.

The curative treatment of oligometastases with radiotherapy remains an area of active investigation. We hypothesise that treating oligometastases with SBRT can prolong life and potentially cure patients, while in patients with multiple lung metastases SBRT can improve quality of life. Fifty patients with lung metastases were treated on this study. Individuals with five or fewer total lesions were treated with curative intent. Individuals with > five metastases were treated palliatively. Most patients (62%) received 5 Gy/fraction for a total of 50 Gy. The number of targets treated per patient ranged from one to five (mean 2.6). Tumor sizes ranged from 0.3–7.7 cm in maximal diameter (median 2.1 cm). Mean follow-up was 18.7 months. Local control of treated lesions was obtained in 42 of 49 evaluable patients (83%). Of the 125 total lesions treated, eight progressed after treatment (94% crude local control). The median overall survival time from time of treatment completion of the curatively treated patients was 23.4 months. The progression-free survival of the same group of patients was 25% and 16% at 12 and 24 months, respectively. Grade 1 toxicity occurred in 35% of all the patients, 6.1% had grade 2 toxicity, and 2% had grade 3 toxicity. Excellent local tumor control rates with low toxicity are seen with SBRT. Median survival time and progression-free survival both appear better than that achieved with standard care alone. Long-term progression-free survival can be seen in a subset of patients when all tumors are targeted

Estimation of complications for linear accelerator radiosurgery with the integrated logistic formula

Radiosurgery techniques permit high doses of single fraction irradiation to be administered to small volumes of tumor with relative sparing of surrounding brain tissue. The tolerance of surrounding normal brain tissue to dose distributions from linear accelerator radiosurgery with different collimator sizes is an important factor that must be estimated by anyone using these treatment techniques. The exponential and linear quadratic versions of the integrated logistic formula were used to estimate the probability of brain necrosis at different doses for radiosurgical dose distributions administered by a 6 MV linear accelerator with a 5 arc technique for collimator sizes from 12.5 to 30 mm in diameter. Dose-volume isoeffect curves for a 3% risk of brain necrosis from linear accelerator radiosurgery were then calculated. These curves approximate those calculated for gamma knife radiosurgery and a published 1% dose-volume isoeffect line predicted for proton beam irradiation. Similar dose-volume isoeffect curves were calculated for single fraction radiosurgery boosts administered after 30 Gy of whole brain irradiation in 12 fractions. The integrated logistic formula appears to be a useful tool for estimating tolerance and providing guidelines for prescribing radiation doses for linear accelerator radiosurgery.

CT-assisted assessment of bladder and rectum dose in gynecological implants

Eight patients who received gynecological implants with Fletcher-Suit type applicators were involved in this study. An orthogonal pair of films and computed tomographic scans were obtained for each patient. In the CT study, judicious use of contrast materials and selective window and level settings permitted clear delineation of the bladder and the rectum boundaries relative to the implanted applicators. In comparison to reference organ doses derived from the orthogonal film pair method, the maximum organ doses estimated from the CT-assisted evaluation were considerably higher, by approximately twofold on the average. The differences between the values estimated from the two methods vary from patient to patient, being highly dependent on the individual anatomy and the geometry of the implanted sources. These preliminary results point to the inaccuracy of the conventional method of estimating organ doses. CT-assisted evaluation may be necessary to accurately calculate organ doses in gynecological applications.

Descriptive Analysis of Oligometastatic Lesions Treated With Curative-Intent Stereotactic Body Radiotherapy

PURPOSE To characterize oligometastases in patients enrolled on two prospective pilot studies, treating oligometastases with hypofractionated stereotactic body radiotherapy and stereotactic radiosurgery to cranial lesions. METHODS AND MATERIALS We describe the characteristics and local control (LC) of 293 lesions in 121 patients with five or fewer metastases treated with stereotactic body radiation and/or cranial stereotactic radiosurgery. For each lesion, the primary cancer site, tumor histology, site of metastasis, gross tumor volume, and prescribed dose were ascertained. The prescribed dose is expressed by the biologically effective dose in 2-Gy fractions (BED2), calculated using the linear quadratic model, assuming an alpha/beta ratio of 10. RESULTS Lung lesions were significantly smaller than other lesions in our cohort, whereas liver lesions were significantly larger, possibly reflecting a detection and/or referral bias. The 2-year and 4-year tumor LC rates were 77% and 73% respectively. A larger gross tumor volume was significantly (p < 0.0001) correlated with worse lesion LC. Lesions originating from primary pancreatic, biliary or liver cancer exhibited significantly poorer LC, as did lesions from colorectal cancer. Lesions from breast cancer were better controlled. A higher BED2 did not correlate with improved tumor control. CONCLUSIONS Stereotactic body radiation to aggressively treat oligometastatic lesions results in good local tumor control. Bulkier lesions are more difficult to control and may benefit from dose escalation.