Andrew D. Vassil

Palliative radiotherapy for bone metastases: An ASTRO evidence-based guideline

PURPOSE To present guidance for patients and physicians regarding the use of radiotherapy in the treatment of bone metastases according to current published evidence and complemented by expert opinion. METHODS AND MATERIALS A systematic search of the National Library of Medicines PubMed database between 1998 and 2009 yielded 4,287 candidate original research articles potentially applicable to radiotherapy for bone metastases. A Task Force composed of all authors synthesized the published evidence and reached a consensus regarding the recommendations contained herein. RESULTS The Task Force concluded that external beam radiotherapy continues to be the mainstay for the treatment of pain and/or prevention of the morbidity caused by bone metastases. Various fractionation schedules can provide significant palliation of symptoms and/or prevent the morbidity of bone metastases. The evidence for the safety and efficacy of repeat treatment to previously irradiated areas of peripheral bone metastases for pain was derived from both prospective studies and retrospective data, and it can be safe and effective. The use of stereotactic body radiotherapy holds theoretical promise in the treatment of new or recurrent spine lesions, although the Task Force recommended that its use be limited to highly selected patients and preferably within a prospective trial. Surgical decompression and postoperative radiotherapy is recommended for spinal cord compression or spinal instability in highly selected patients with sufficient performance status and life expectancy. The use of bisphosphonates, radionuclides, vertebroplasty, and kyphoplasty for the treatment or prevention of cancer-related symptoms does not obviate the need for external beam radiotherapy in appropriate patients. CONCLUSIONS Radiotherapy is a successful and time efficient method by which to palliate pain and/or prevent the morbidity of bone metastases. This Guideline reviews the available data to define its proper use and provide consensus views concerning contemporary controversies or unanswered questions that warrant prospective trial evaluation.

Long-term outcomes of Gamma Knife radiosurgery in patients with vestibular schwannomas

OBJECT The authors sought to determine the long-term tumor control and side effects of Gamma Knife radiosurgery (GKRS) in patients with vestibular schwannomas (VS). METHODS One hundred seventeen patients with VS underwent GKRS between January 1997 and February 2003. At the time of analysis, at least 5 years had passed since GKRS in all patients. The mean patient age was 60.9 years. The mean maximal tumor diameter was 1.77 ± 0.71 cm. The mean tumor volume was 1.95 ± 2.42 ml. Eighty-two percent of lesions received 1300 cGy and 14% received 1200 cGy. The median dose homogeneity ratio was 1.97 and the median dose conformality ratio was 1.78. Follow-up included MR imaging or CT scanning approximately every 6-12 months. Rates of progression to surgery were calculated using the Kaplan-Meier method. RESULTS Of the 117 patients in whom data were analyzed, 103 had follow-up MR or CT images and 14 patients were lost to follow-up. Fifty-three percent of patients had stable tumors and 37.9% had a radiographically documented response. Imaging-documented tumor progression was present in 8 patients (7.8%), but in 3 of these the lesion eventually stabilized. Only 5 patients required a neurosurgical intervention. The estimated 1-, 3-, and 5-year rates of progression to surgery were 1, 4.6, and 8.9%, respectively. One patient (1%) developed trigeminal neuropathy, 4 patients (5%) developed permanent facial neuropathy, 3 patients (4%) reported vertigo, and 7 patients (18%) had new gait imbalance following GKRS. CONCLUSIONS Gamma Knife radiosurgery results in excellent local control rates with minimal toxicity for patients with VS. The authors recommend standardized follow-up to gain a better understanding of the long-term effects of GKRS.

ACR Appropriateness Criteria® non-spine bone metastases.

Bone is one of the most common sites of metastatic spread of malignancy, with possible deleterious effects including pain, hypercalcemia, and pathologic fracture. External beam radiotherapy (EBRT) remains the mainstay for treatment of painful bone metastases. EBRT may be combined with other local therapies like surgery or with systemic treatments like chemotherapy, hormonal therapy, osteoclast inhibitors, or radiopharmaceuticals. EBRT is not commonly recommended for patients with asymptomatic bone metastases unless they are associated with a risk of pathologic fracture. For those who do receive EBRT, appropriate fractionation schemes include 30 Gy in 10 fractions, 24 Gy in 6 fractions, 20 Gy in 5 fractions, or a single 8 Gy fraction. Single fraction treatment maximizes convenience, while fractionated treatment courses are associated with a lower incidence of retreatment. The appropriate postoperative dose fractionation following surgical stabilization is uncertain. Reirradiation with EBRT may be safe and provide pain relief, though retreatment might create side effect risks which warrant its use as part of a clinical trial. All patients with bone metastases should be considered for concurrent management by a palliative care team, with patients whose life expectancy is less than six months appropriate for hospice evaluation. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every two years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR Appropriateness Criteria® Metastatic Epidural Spinal Cord Compression and Recurrent Spinal Metastasis.

Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency and if left untreated, permanent paralysis will ensue. The treatment of MESCC is governed by disease, patient, and treatment factors. Patients preferences and goals of care are to be weighed into the treatment plan. Ideally, a patient with MESCC is evaluated by an interdisciplinary team promptly to determine the urgency of the clinical scenario. Treatment recommendations must take into consideration the risk-benefit profiles of surgical intervention and radiotherapy for the particular individuals circumstance, including neurologic status, performance status, extent of epidural disease, stability of the spine, extra-spinal disease status, and life expectancy. In patients with high spinal instability neoplastic score (SINS) or retropulsion of bone fragments in the spinal canal, surgical intervention should be strongly considered. The rate of development of motor deficits from spinal cord compression may be a prognostic factor for ultimate functional outcome, and should be taken into account when a treatment recommendation is made. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria® follow-up and retreatment of brain metastases

Multiple options for retreatment are available, which include whole-brain radiation therapy, stereotactic radiosurgery, surgery, chemotherapy, and supportive care. Size, number, timing, location, histology, performance status, and extracranial disease status all need to be carefully considered when choosing a treatment modality. There are no randomized trials examining the retreatment of brain metastases. Repeat whole-brain radiation has been examined in a single-institution experience, showing the potential for clinical responses in selected patients. Local control rates as high as 91% using stereotactic radiosurgery for relapses after whole-brain radiation are reported. Surgery can be indicated in progressive and/or hemorrhagic lesions causing mass effect. The role of chemotherapy in the recurrent setting is limited but some agents may have activity on the basis of experiences on a smaller scale. Supportive care continues to be an important option, especially in those with a poor prognosis. Follow-up for brain metastases patients is discussed, examining the modality, frequency of imaging, and imaging options in differentiating treatment effect from recurrence. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of the current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

ACR appropriateness criteria® pre-irradiation evaluation and management of brain metastases

Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.

Evolving Paradigm of Radiotherapy for High-Risk Prostate Cancer: Current Consensus and Continuing Controversies

High-risk prostate cancer is an aggressive form of the disease with an increased risk of distant metastasis and subsequent mortality. Multiple randomized trials have established that the combination of radiation therapy and long-term androgen deprivation therapy improves overall survival compared to either treatment alone. Standard of care for men with high-risk prostate cancer in the modern setting is dose-escalated radiotherapy along with 2-3 years of androgen deprivation therapy (ADT). There are research efforts directed towards assessing the efficacy of shorter ADT duration. Current research has been focused on assessing hypofractionated and stereotactic body radiation therapy (SBRT) techniques. Ongoing randomized trials will help assess the utility of pelvic lymph node irradiation. Research is also focused on multimodality therapy with addition of a brachytherapy boost to external beam radiation to help improve outcomes in men with high-risk prostate cancer.

Feasibility of using nonflat photon beams for whole‐breast irradiation with breath hold

Removing a flattening filter or replacing it with a thinner filter alters the characteristics of a photon beam, creating a forward peaked intensity profile to make the photon beam nonflat. This study is to investigate the feasibility of applying nonflat photon beams to the whole‐breast irradiation with breath holds for a potential of delivery time reduction during the gated treatment. Photon beams of 6 MV with flat and nonflat intensity profiles were commissioned. Fifteen patients with early‐stage breast cancer, who received whole‐breast radiation without breathing control, were retrospectively selected for this study. For each patient, three plans were created using a commercial treatment planning system: (a) the clinically approved plan using forward planning method (FP); (b) a hybrid intensity‐modulated radiation therapy (IMRT) plan where the flat beam open fields were combined with the nonflat beam IMRT fields using direct aperture optimization method (mixed DAO); (c) a hybrid IMRT plan where both open and IMRT fields were from nonflat beams using direct aperture optimization (nonflat DAO). All plans were prescribed for ≥95% of the breast volume receiving the prescription dose of 50 Gy (2.0 Gy per fraction). In comparison, all plans achieved a similar dosimetric coverage to the targeted volume. The average homogeneity index of the FP, mixed DAO, and nonflat DAO plans were 0.882±0.024, 0.879±0.023, and 0.867±0.027, respectively. The average percentage volume of V105 was 57.66%±5.21%, 34.67%±4.91%, 41.64%±5.32% for the FP, mixed, and nonflat DAO plans, respectively. There was no significant difference (p>0.05) observed for the defined endpoint doses in organs at risk (OARs). In conclusion, both mixed DAO and nonflat DAO plans can achieve similar plan quality as the clinically approved FP plan, measured by plan homogeneity and endpoint doses to the ORAs. Nonflat beam plans may reduce treatment time in breath‐hold treatment, especially for hypofractionated treatment. PACS number: 87.55

Daily dose monitoring with atlas-based auto-segmentation on diagnostic quality CT for prostate cancer.

PURPOSE To evaluate the feasibility of daily dose monitoring using a patient specific atlas-based autosegmentation method on diagnostic quality verification images. METHODS Seven patients, who were treated for prostate cancer with intensity modulated radiotherapy under daily imaging guidance of a CT-on-rails system, were selected for this study. The prostate, rectum, and bladder were manually contoured on the first six and last seven sets of daily verification images. For each patient, three patient specific atlases were constructed using manual contours from planning CT alone (1-image atlas), planning CT plus first three verification CTs (4-image atlas), and planning CT plus first six verification CTs (7-image atlas). These atlases were subsequently applied to the last seven verification image sets of the same patient to generate the auto-contours. Daily dose was calculated by applying the original treatment plans to the daily beam isocenters. The autocontours and manual contours were compared geometrically using the dice similarity coefficient (DSC), and dosimetrically using the dose to 99% of the prostate CTV (D99) and the D5 of rectum and bladder. RESULTS The DSC of the autocontours obtained with the 4-image atlases were 87.0% ± 3.3%, 84.7% ± 8.6%, and 93.6% ± 4.3% for the prostate, rectum, and bladder, respectively. These indices were higher than those from the 1-image atlases (p < 0.01) and comparable to those from the 7-image atlases (p > 0.05). Daily prostate D99 of the autocontours was comparable to those of the manual contours (p = 0.55). For the bladder and rectum, the daily D5 were 95.5% ± 5.9% and 99.1% ± 2.6% of the planned D5 for the autocontours compared to 95.3% ± 6.7% (p = 0.58) and 99.8% ± 2.3% (p < 0.01) for the manual contours. CONCLUSIONS With patient specific 4-image atlases, atlas-based autosegmentation can adequately facilitate daily dose monitoring for prostate cancer.

SU‐GG‐T‐132: Application of Non Flat Beams for Breast Radiotherapy Using Direct Aperture Optimization

Purpose: Non‐flat beam is attractive for SBRT and IMRT delivery. This study is to investigate whether non‐flat beam can achieve uniform dose distribution for whole breast irradiation. Method and Materials: A 6MV non‐flat and flat beams were commissioned in an Oncor Linac (Siemens). Fifteen early‐stage breast cancer patients were selected. For each patient, three plans were generated for comparison: (a) clinically approved forward planning (FP); (b) mixed open fields using flat beams with direct aperture openand DAO IMRT fields using non‐flat beams (mixed DAO); (c) All open and DAO IMRT fields using non‐flat beams (non‐flat DAO). All plans were prescribed for >95% of the breast volume receiving the prescription dose. Plan quality was evaluated according to homogeneity index (HI), conformality index (COIN), D95%, V105% and D1cc as well as V20Gy to ipsilateral lung, V1Gy to contralateral breast and V25Gy to heart for left breast. All treatment plans were created using Pinnacle 8.0. Results: No significant difference was observed for COIN among all plans (all p>0.05). Average HIs of FP, mixed DAO, and non‐flat DAO were 0.88±0.01, 0.88±0.01 and 0.87±0.01, respectively. The mixed DAO had significantly lower V105% than FP and non‐flat DAO. For organs at risk (OAR), no significant difference was observed. For D1cc, non‐flat DAO was significantly higher than FP and mixed DAO (p<0.005). The lowest MU required was FP plan without wedges, followed by mixed DAO, FP with wedges, and non‐flat DAO plans. Conclusion: Both mixed DAO and non‐flat DAO plans can achieve equivalent planning quality as the clinically approved flat‐beam FP plans. In addition, the mixed DAO plan has smaller hotspot area than non‐flat DAO and FP while dose to OARs is not significantly different. Overall, non‐flat beams are applicable to breast RT.