The NOMS framework: approach to the treatment of spinal metastatic tumors.

BACKGROUND: Spinal metastases frequently arise in patients with cancer. Modern oncology provides numerous treatment options that include effective systemic, radiation, and surgical options. We delineate and provide the evidence for the neurologic, oncologic, mechanical, and systemic (NOMS) decision framework, which is used at Memorial Sloan-Kettering Cancer Center to determine the optimal therapy for patients with spine metastases. METHODS: We provide a literature review of the integral publications that serve as the basis for the NOMS framework and report the results of systematic implementation of the NOMS-guided treatment. RESULTS: The NOMS decision framework consists of the neurologic, oncologic, mechanical, and systemic considerations and incorporates the use of conventional external beam radiation, spinal stereotactic radiosurgery, and minimally invasive and open surgical interventions. Review of radiation oncology and surgical literature that examine the outcomes of treatment of spinal metastatic tumors provides support for the NOMS decision framework. Application of the NOMS paradigm integrates multimodality therapy to optimize local tumor control, pain relief, and restoration or preservation of neurologic function and minimizes morbidity in this often systemically ill patient population. CONCLUSION: NOMS paradigm provides a decision framework that incorporates sentinel decision points in the treatment of spinal metastases. Consideration of the tumor sensitivity to radiation in conjunction with the extent of epidural extension allows determination of the optimal radiation treatment and the need for surgical decompression. Mechanical stability of the spine and the systemic disease considerations further help determine the need and the feasibility of surgical intervention.

Favourable long-term outcomes with brachytherapy-based regimens in men ≤60 years with clinically localized prostate cancer.

OBJECTIVE: To report long-term outcomes of men ≤60 years treated with brachytherapy (BT) for low- and intermediate-risk prostate cancer. PATIENTS AND METHODS: Of 1655 patients treated with BT for clinically localized prostate cancer between January 1998 and May 2008 at Memorial Sloan-Kettering Cancer Center, 236 patients with National Comprehensive Cancer Network low- (n = 178) or intermediate-risk (n = 58) prostate cancer were ≤60 years old with a 3-year minimum follow-up, and represent the subjects of this report. Brachytherapy was given either as monotherapy (n = 169) or with external beam radiation therapy (EBRT; n = 67). Forty-four patients (19%) received neoadjuvant cytoreductive hormone therapy. The 'nadir+2' definition was used for prostate-specific antigen (PSA) recurrence. Common Terminology Criteria for Acute Events (CTCAE) v 3.0 was used to grade genitourinary (GU) and gastrointestinal (GI) toxicity. Potency was defined as the ability to obtain an erection suitable for intercourse or an International Index of Erectile Function score ≥ 22. The Kaplan-Meier method and Cox regression were used for statistical analysis. The median follow-up was 83 months. RESULTS: The 8-year PSA relapse-free survival (RFS), cancer-specific and overall survival rates for the entire cohort were 96, 99 and 96%, respectively. For patients with low-risk disease, the 8-year PSA RFS rate was 97% and for intermediate-risk patients it was 94% (P = 0.34). There was no difference in PSA RFS between BT alone and combined therapy (P = 0.17). Late grade ≥ 2 GU and GI toxicity was 14 and 3%, respectively. Of 150 patients potent before treatment, 76 (51%) were potent at last follow-up, with 50/76 (66%) using no medication. There was no significant difference in post-treatment potency between BT alone and BT with EBRT (P = 0.74). CONCLUSIONS: Brachytherapy provides patients aged ≤ 60 years with low- and intermediate-risk prostate cancer with excellent outcomes and has a low risk of significant long-term GU or GI morbidity. Erectile function is preserved in >50% of patients and the majority do not require erectile dysfunction medication.

Salvage prostate brachytherapy in radiorecurrent prostate cancer: An international Delphi consensus study.

BACKGROUND AND PURPOSE: Local recurrences after previous radiotherapy (RT) are increasingly being identified in biochemically recurrent prostate cancer. Salvage prostate brachytherapy (BT) is an effective and well tolerated treatment option. We sought to generate international consensus statements on the use and preferred technical considerations for salvage prostate BT. MATERIALS AND METHODS: International experts in salvage prostate BT were invited (n = 34) to participate. A three-round modified Delphi technique was utilized, with questions focused on patient- and cancer-specific criteria, type and technique of BT, and follow-up. An a priori threshold for consensus of ≥ 75% was set, with a majority opinion being ≥ 50%. RESULTS: Thirty international experts agreed to participate. Consensus was achieved for 56% (18/32) of statements. Consensus was achieved in several areas of patient selection: 1) A minimum of 2-3 years from initial RT to salvage BT; 2) MRI and PSMA PET should be obtained; and 3) Both targeted and systematic biopsies should be performed. Several areas did not reach consensus: 1) Maximum T stage/PSA at time of salvage; 2) Utilization/duration of ADT; 3) Appropriateness of combining local salvage with SABR for oligometastatic disease and 4) Repeating a second course of salvage BT. A majority opinion preferred High Dose-Rate salvage BT, and indicated that both focal and whole gland techniques could be appropriate. There was no single preferred dose/fractionation. CONCLUSION: Areas of consensus within our Delphi study may serve as practical advice for salvage prostate BT. Future research in salvage BT should address areas of controversy identified in our study.

Secondary cancers after intensity-modulated radiotherapy, brachytherapy and radical prostatectomy for the treatment of prostate cancer: incidence and cause-specific survival outcomes according to the initial treatment intervention.

UNLABELLED: Study Type--Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Radiation Therapy for prostate cancer can increase the risk for the development of second cancers after treatment. This study highlights the fact that such second cancers within the pelvis do occur but are not as common as previously reported. In this report we also note that even among patients who develop second cancers, if detected earlier, the majority are alive 5 years after the diagnosis. OBJECTIVE: • To report on the incidence of secondary malignancy (SM) development after external beam radiotherapy (EBRT) and brachytherapy (BT) for prostate cancer and to compare this with a cohort contemporaneously treated with radical prostatectomy (RP). MATERIALS AND METHODS: • Between 1998 and 2001, 2658 patients with localized prostate cancer were treated with RP (n = 1348), EBRT (n = 897) or BT (n = 413). • Using the RP cohort as a control we compared the incidence of SMs, such as rectal or bladder cancers noted within the pelvis, and the incidence of extrapelvic SMs. RESULTS: • The 10-year SM-free survival for the RP, BT and EBRT cohorts were 89%, 87%, and 83%, respectively (RP vs EBRT, P = 0.002; RP vs BT, P = 0.37). • The 10-year likelihoods for bladder or colorectal cancer SM development in the RP, BT and EBRT groups were 3%, 2% and 4%, respectively (P = 0.29). • Multivariate analysis of predictors for development of all SMs showed that older age (P = 0.01) and history of smoking (P < 0.001) were significant predictors for the development of a SM, while treatment intervention was not found to be a significant variable. • Among 243 patients who developed a SM, the 5-year likelihood of SM-related mortality among patients with SMs in the EBRT and BT groups was 43.7% and 15.6%, respectively, compared with 26.3% in the RP cohort; P = 0.052). CONCLUSIONS: • The incidence of SM after radiotherapy was not significantly different from that after RP when adjusted for patient age and smoking history. • The incidence of bladder and rectal cancers was low for both EBRT- and BT-treated patients. • Among patients who developed a SM, the likelihood of mortality related to the SM was not significantly different among the treatment cohorts.

Incorporation of treatment plan spatial and temporal dose patterns into a prostate intrafractional motion management strategy.

PURPOSE: Periodic MV∕KV radiographs taken during volumetric modulated arc therapy (VMAT) for hypofractionated treatment provide guidance in intrafractional motion management. The choice of imaging frequency and timing are key components in delivering the desired dose while reducing associated overhead such as imaging dose, preparation, and processing time. In this project the authors propose a paradigm with imaging timing and frequency based on the spatial and temporal dose patterns of the treatment plan. METHODS: A number of control points are used in treatment planning to model VMAT delivery. For each control point, the sensitivity of individual target or organ-at-risk dose to motion can be calculated as the summation of dose degradations given the organ displacements along a number of possible motion directions. Instead of acquiring radiographs at uniform time intervals, MV∕KV image pairs are acquired indexed to motion sensitivity. Five prostate patients treated via hypofractionated VMAT are included in this study. Intrafractional prostate motion traces from the database of an electromagnetic tracking system are used to retrospectively simulate the VMAT delivery and motion management. During VMAT delivery simulation patient position is corrected based on the radiographic findings via couch movement if target deviation violates a patient-specific 3D threshold. The violation rate calculated as the percentage of traces failing the clinical dose objectives after motion correction is used to evaluate the efficacy of this approach. RESULTS: Imaging indexed to a 10 s equitime interval and correcting patient position accordingly reduces the violation rate to 19.5% with intervention from 44.5% without intervention. Imaging indexed to the motion sensitivity further reduces the violation rate to 12.1% with the same number of images. To achieve the same 5% violation rate, the imaging incidence can be reduced by 40% by imaging indexed to motion sensitivity instead of time. CONCLUSIONS: The simulation results suggest that image scheduling according to the characteristics of the treatment plan can improve the efficiency of intrafractional motion management. Using such a technique, the accuracy of delivered dose during image-guided hypofractionated VMAT treatment can be improved.

ACR-ABS-ASTRO Practice Parameter for Transperineal Permanent Brachytherapy of Prostate Cancer.

AIM/OBJECTIVES/BACKGROUND: The American College of Radiology (ACR), American Brachytherapy Society (ABS), and American Society for Radiation Oncology (ASTRO) have jointly developed the following practice parameter for transperineal permanent brachytherapy of prostate cancer. Transperineal permanent brachytherapy of prostate cancer is the interstitial implantation of low-dose rate radioactive seeds into the prostate gland for the purpose of treating localized prostate cancer. METHODS: This practice parameter was developed according to the process described under the heading The Process for Developing ACR Practice Parameters and Technical Standards on the ACR website (https://www.acr.org/Clinical-Resources/Practice-Parameters-and-Technical-Standards) by the Committee on Practice Parameters-Radiation Oncology of the Commission on Radiation Oncology, in collaboration with ABS and ASTRO. RESULTS: This practice parameter provides a framework for the appropriate use of low-dose rate brachytherapy in the treatment of prostate cancer either as monotherapy or as part of a treatment regimen combined with external-beam radiation therapy. The practice parameter defines the qualifications and responsibilities of all involved radiation oncology personnel, including the radiation oncologist, medical physicist, dosimetrist, radiation therapist, and nursing staff. Patient selection criteria and the utilization of supplemental therapies such as external-beam radiation therapy and androgen deprivation therapy are discussed. The logistics of the implant procedure, postimplant dosimetry assessment, and best practices with regard to safety and quality control are presented. CONCLUSIONS: Adherence to established standards can help to ensure that permanent prostate brachytherapy is delivered in a safe and efficacious manner.

Determination of action thresholds for electromagnetic tracking system-guided hypofractionated prostate radiotherapy using volumetric modulated arc therapy.

PURPOSE: Hypofractionated prostate radiotherapy may benefit from both volumetric modulated are therapy (VMAT) due to shortened treatment time and intrafraction real-time monitoring provided by implanted radiofrequency(RF) transponders. The authors investigate dosimetrically driven action thresholds (whether treatment needs to be interrupted and patient repositioned) in VMAT treatment with electromagnetic (EM) tracking. METHODS: VMAT plans for five patients are generated for prescription doses of 32.5 and 42.5 Gy in five fractions. Planning target volume (PTV) encloses the clinical target volume (CTV) with a 3 mm margin at the prostate-rectal interface and 5 mm elsewhere. The VMAT delivery is modeled using 180 equi-spaced static beams. Intrafraction prostate motion is simulated in the plan by displacing the beam isocenter at each beam assuming rigid organ motion according to a previously recorded trajectory of the transponder centroid. The cumulative dose delivered in each fraction is summed over all beams. Two sets of 57 prostate motion trajectories were randomly selected to form a learning and a testing dataset. Dosimetric end points including CTV D95%, rectum wall D1cc, bladder wall D1cc, and urethra Dmax, are analyzed against motion characteristics including the maximum amplitude of the anterior-posterior (AP), superior-inferior (SI), and left-right components. Action thresholds are triggered when intrafraction motion causes any violations of dose constraints to target and organs at risk (OAR), so that treatment is interrupted and patient is repositioned. RESULTS: Intrafraction motion has a little effect on CTV D95%, indicating PTV margins are adequate. Tight posterior and inferior action thresholds around 1 mm need to be set in a patient specific manner to spare organs at risk, especially when the prescription dose is 42.5 Gy. Advantages of setting patient specific action thresholds are to reduce false positive alarms by 25% when prescription dose is low, and increase the sensitivity of detecting dose limits violations by 30% when prescription dose is high, compared to a generic 2 mm action box. The sensitivity and specificity calculated from the testing dataset are consistent to the learning set, which indicates that the patient specific approach is reliable and reproducible within the scope of the prostate database. CONCLUSIONS: This work introduces a formalism for ensuring a VMAT delivery meets the most clinically important dose requirements by using patient specific and dosimetric-driven action thresholds to hold the beam and reposition the patient when necessary. Such methods can provide improved sensitivity and specificity compared to conventional methods, which assume directionally symmetric action thresholds.

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement.

PURPOSE: The purpose of this guideline is to present evidence-based consensus recommendations for low dose rate (LDR) permanent seed brachytherapy for the primary treatment of prostate cancer. METHODS AND MATERIALS: The American Brachytherapy Society convened a task force for addressing key questions concerning ultrasound-based LDR prostate brachytherapy for the primary treatment of prostate cancer. A comprehensive literature search was conducted to identify prospective and multi-institutional retrospective studies involving LDR brachytherapy as monotherapy or boost in combination with external beam radiation therapy with or without adjuvant androgen deprivation therapy. Outcomes included disease control, toxicity, and quality of life. RESULTS: LDR prostate brachytherapy monotherapy is an appropriate treatment option for low risk and favorable intermediate risk disease. LDR brachytherapy boost in combination with external beam radiation therapy is appropriate for unfavorable intermediate risk and high-risk disease. Androgen deprivation therapy is recommended in unfavorable intermediate risk and high-risk disease. Acceptable radionuclides for LDR brachytherapy include iodine-125, palladium-103, and cesium-131. Although brachytherapy monotherapy is associated with increased urinary obstructive and irritative symptoms that peak within the first 3 months after treatment, the median time toward symptom resolution is approximately 1 year for iodine-125 and 6 months for palladium-103. Such symptoms can be mitigated with short-term use of alpha blockers. Combination therapy is associated with worse urinary, bowel, and sexual symptoms than monotherapy. A prostate specific antigen <= 0.2 ng/mL at 4 years after LDR brachytherapy may be considered a biochemical definition of cure. CONCLUSIONS: LDR brachytherapy is a convenient, effective, and well-tolerated treatment for prostate cancer.

Prospective Peer Review in Radiation Therapy Treatment Planning: Long-Term Results From a Longitudinal Study.

PURPOSE: To present the longitudinal results of a prospective peer review evaluation system (PES) before treatment planning. METHODS AND MATERIALS: All cases undergoing radiation therapy (RT) at high-volume academic institutions were graded in daily prospective multidisciplinary contouring rounds (CRs). The clinical suitability for RT, prescription, contours, and written directives were peer reviewed, compared with departmental care pathways, and recorded in a prospective database. Grades were assigned as follows: A (score 4.0) = no deficiencies; B (3.0) = minor modifications of the planning target volume, organs at risk, written directives, or a prescription/care pathway mismatch; and C (2.0) = incomplete target volume or organ-at-risk contours, unsuitable use or inappropriate planned administration of RT, significant contour modifications, prescription changes, or laterality modifications. Information was pooled to determine pretreatment planning work performance by assigning a grade point average (GPA) for each physician as well as compositely. RESULTS: A total of 11,843 treatment plans from 7854 patients were reviewed using the PES from September 2013 to May 2018. Twenty-seven point nine percent of cases (n = 3303) required modifications before treatment planning commenced. The overall breakdown of grades was 72.1% As, 21.7% Bs, and 6.2% Cs. The median physician CR GPA was 3.60 (average 3.7) with a range of 3.0 to 3.9. Seventy-five percent of physicians demonstrated improvement of their CR GPA since inception of the program, and all physicians demonstrated a drop in the percentage of cases that were assigned a grade of C. CONCLUSIONS: The PES can transparently quantify clinical performance in a single metric. The PES was impactful, with 75% of physicians demonstrating improvement in their CR GPA over time. In contrast to traditional chart rounds, this peer review was meaningful when done before planning commenced, a trend that was observed throughout the study period. Twenty-seven point nine percent of all cases required modification before starting treatment planning, and 6.2% of cases required significant remediation.

The American Brachytherapy Society prostate brachytherapy LDR/HDR simulation workshops: Hands-on, step-by-step training in the process of quality assurance.

PURPOSE: Education and training on prostate brachytherapy for radiation oncology and medical physics residents in the United States is inadequate, resulting in fewer competent radiation oncology personnel to perform implants, and is a factor in the subsequent decline of an important, potentially curative cancer treatment modality for patients with cancer. The American Brachytherapy Society (ABS) leadership has recognized the need to establish a sustainable medical simulation low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy workshop program that includes physician-physicist teams to rapidly translate knowledge to establish high-quality brachytherapy programs. METHODS: The ABS, in partnership with industry and academia, has held three radiation oncology team-based LDR/HDR workshops composed of physician-physicist teams in Chicago in 2017, in Houston in 2018, and in Denver in 2019. The predefined key metric of success is the number of attendees who returned to their respective institutions and were actively performing brachytherapy within 6 months of the prostate brachytherapy workshop. RESULTS: Of the 111 physician/physicist teams participating in the Chicago, Houston, and Denver prostate brachytherapy workshops, 87 (78%) were actively performing prostate brachytherapy (51 [59%] HDR and 65 [75%] LDR). CONCLUSIONS: The ABS prostate brachytherapy LDR/HDR simulation workshop has provided a successful education and training structure for medical simulation of the critical procedural steps in quality assurance to shorten the learning curve for delivering consistently high-quality brachytherapy implants for patients with prostate cancer. An ABS initiative, intended to bend the negative slope of the brachytherapy curve, is currently underway to train 300 new competent brachytherapy teams over the next 10 years.

Nodular Leptomeningeal Disease-A Distinct Pattern of Recurrence After Postresection Stereotactic Radiosurgery for Brain Metastases: A Multi-institutional Study of Interobserver Reliability.

PURPOSE: For brain metastases, surgical resection with postoperative stereotactic radiosurgery is an emerging standard of care. Postoperative cavity stereotactic radiosurgery is associated with a specific, underrecognized pattern of intracranial recurrence, herein termed nodular leptomeningeal disease (nLMD), which is distinct from classical leptomeningeal disease. We hypothesized that there is poor consensus regarding the definition of LMD, and that a formal, self-guided training module will improve interrater reliability (IRR) and validity in diagnosing LMD. METHODS AND MATERIALS: Twenty-two physicians at 16 institutions, including 15 physicians with central nervous system expertise, completed a 2-phase survey that included magnetic resonance imaging and treatment information for 30 patients. In the "pretraining" phase, physicians labeled cases using 3 patterns of recurrence commonly reported in prospective studies: local recurrence (LR), distant parenchymal recurrence (DR), and LMD. After a self-directed training module, participating physicians completed the "posttraining" phase and relabeled the 30 cases using the 4 following labels: LR, DR, classical leptomeningeal disease, and nLMD. RESULTS: IRR increased 34% after training (Fleiss' Kappa K = 0.41 to K = 0.55, P < .001). IRR increased most among non-central nervous system specialists (+58%, P < .001). Before training, IRR was lowest for LMD (K = 0.33). After training, IRR increased across all recurrence subgroups and increased most for LMD (+67%). After training, ≥27% of cases initially labeled LR or DR were later recognized as nLMD. CONCLUSIONS: This study highlights the large degree of inconsistency among clinicians in recognizing nLMD. Our findings demonstrate that a brief self-guided training module distinguishing nLMD can significantly improve IRR across all patterns of recurrence, and particularly in nLMD. To optimize outcomes reporting, prospective trials in brain metastases should incorporate central imaging review and investigator training.

Outcomes of a Dose-Escalated Stereotactic Body Radiation Phase 1 Trial for Patients With Low- and Intermediate-Risk Prostate Cancer.

PURPOSE: This study presents a prospective phase 1, institutional review board-approved dose-escalated stereotactic body radiation therapy trial for prostate cancer (CaP) to assess the impact of dose level on quality of life, toxicity, and clinical outcomes. METHODS AND MATERIALS: From 2011 to 2016, 26 patients with low- and intermediate-risk CaP received 40, 45, and 50 Gy in 5 fractions to the prostate in cohorts of 9, 10, and 7 patients. Self-reported quality of life was prospectively measured from the Expanded Prostate Cancer Index Composite and American Urological Association. Common Terminology Criteria for Adverse Events (version 4.03) data were collected to observe acute and late toxicities. The Phoenix definition was used to calculate outcome. No patients received androgen deprivation therapy. RESULTS: Median follow-up was 67.2 months (range, 71-230 months). There was an increase in Expanded Prostate Cancer Index Composite and American Urological Association scores followed by a return to baseline over 2 years for all cohorts. There were no grade 3 or higher toxicities or significant differences in toxicity between treatment arms. The prostate-specific antigen (PSA) nadir was significantly lower in the 45-Gy and 50-Gy cohorts when compared with the 40-Gy cohort (P < .05). Two biochemical failures were observed in the 40-Gy arm after 43 and 62 months, resulting in a freedom from biochemical failure rate of 92%. PSA survival was 100%, and actuarial overall survival was 96%. PSA nadir was 0.6, 0.1, and 0.1 ng/mL, in the 40-Gy, 45-Gy, and 50-Gy cohorts, respectively. CONCLUSIONS: This prospective, phase 1 dose-escalation study of stereotactic body radiation therapy for CaP identified acceptable genitourinary and gastrointestinal toxicity for each dose level of 40, 45, and 50 Gy. Although there was no difference in biochemical failure between the groups, we showed that higher doses of 45 and 50 Gy are associated with improved PSA nadir. The results of this study will be used to develop a larger prospective study to confirm the findings.

Impact of Multi-Institutional Prospective Peer Review on Target and Organ-at-Risk Delineation in Radiation Therapy.

PURPOSE: Peer review is an essential component of quality assurance programs in radiation oncology. The purpose of this work was to assess whether peer reviewers recommend expansion or reduction of planning target volumes (PTVs) and organs at risk (OARs) in prospective multidisciplinary daily contour rounds. METHODS AND MATERIALS: The peer group evaluated the appropriateness of PTVs and OARs for each case according to evidence-based departmental directives. We reviewed 7645 cases that presented between September 2013 and March 2017. We isolated recommendations for PTV/OAR modification and classified each as expansion, reduction, both, or indeterminate. Recommendations were analyzed by technique, site, and physician experience. RESULTS: Eight junior and 7 senior radiation oncologists were included. PTV or OAR modifications were recommended for 750 of 7645 prescriptions (9.7%). The peer group recommended PTV modifications for 534 prescriptions (7.0%): There were 309 expansions (57.9%), 115 reductions (21.5%), 15 both (2.8%), and 95 indeterminate (17.8%). Reasons for PTV expansions included increased nodal coverage and inadequate margins as a result of motion. The peer group recommended OAR modifications for 216 prescriptions (2.8%): There were 102 expansions (47.2%), 23 reductions (10.6%), 2 both (0.9%), and 89 indeterminate (41.2%). Reasons for OAR expansions included missing critical structures and inadequate extent as per departmental standardization. Head and neck represented the largest percentage of PTV recommendations (28.8%). Intensity modulated radiation therapy plans received the most PTV and OAR recommendations (66.8% and 74.5%, respectively). The recommendation rate for senior and junior faculty was 43% and 28%, respectively. CONCLUSIONS: Peer review resulted in recommendations for PTV or OAR change for approximately 10% of cases. Expansions of PTV were recommended >2.5 times more often than reductions and >3 times more often than OAR expansions. This general trend was identified for treatment technique, site, and physician experience. Prospective peer review could yield systematically larger volumes, which could affect multicenter clinical trials.

Five-Year Outcomes of a Phase 1 Dose-Escalation Study Using Stereotactic Body Radiosurgery for Patients With Low-Risk and Intermediate-Risk Prostate Cancer.

PURPOSE: To report toxicity outcomes, prostate-specific antigen (PSA) relapse, and cumulative incidence posttreatment biopsy results among patients treated on a prospective dose escalation study using ultra-hypofractionated stereotactic body radiation therapy (SBRT) for patients with low- and intermediate-risk prostate cancer. METHODS AND MATERIALS: A total of 136 patients were enrolled in a phase 1 dose-escalation study to determine the tolerance of escalating radiation dose levels of SBRT for the treatment of localized prostate cancer. The initial dose level was 32.5 Gy in 5 fractions, and doses were then sequentially escalated to 35 Gy, 37.5 Gy, and 40 Gy. Eligibility criteria included only patients with low and intermediate risk, and the maximum prostate volume was 60 cm3. Patients treated with neoadjuvant androgen deprivation were excluded. The median follow-up in survivors for the 4 dose levels was 5.9, 5.4, 4.1, and 3.5 years, respectively. RESULTS: The incidence of acute grade 2 rectal toxicities for dose levels 1 to 4 were 0%, 2.9%, 2.8%, and 11.4% respectively. No grade 3 or 4 acute rectal toxicities were observed. The incidence of acute grade 2 urinary toxicities for dose levels 1 to 4 were 16.7%, 22.9%, 8.3%, and 17.1%, respectively. No grade 3 or 4 acute urinary toxicities were observed. No grade 2 or higher rectal toxicities were observed. The incidence of late grade 2 urinary toxicities for dose levels 1 to 4 was 23.3%, 25.7%, 27.8%, and 31.4%, respectively. Only 1 late grade 3 urinary toxicity (urethral stricture) developed in the 40-Gy dose arm; the stricture was corrected with transurethral resection. No grade 4 late urinary toxicity was observed. The 5-year cumulative incidence of prostate-specific antigen failure for dose levels 1 to 4 was 15%, 6%, 0%, and 0%. The incidence of a 2-year positive posttreatment biopsy was 47.6%, 19.2%, 16.7%, and 7.7%, respectively for the 4 dose arms (P = .013). CONCLUSIONS: SBRT doses ranging from 32.5 to 40 Gy in 5 fractions were well tolerated without severe urinary or rectal toxicities. Biopsy outcomes suggest improved rates of tumor clearance observed with higher doses.

The current state of randomized clinical trial evidence for prostate brachytherapy.

Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summarize all available randomized data to support the optimal use of prostate brachytherapy. Evidence from completed randomized controlled trials is the focus of this review with a presentation also of important ongoing trials. Gaps in knowledge are identified where future investigation may be fruitful with intent to inspire well-designed prospective studies with standardized treatment that focuses on improving oncological outcomes, reducing morbidity, or maintaining quality of life.

EAU-EANM-ESTRO-ESUR-SIOG Prostate Cancer Guideline Panel Consensus Statements for Deferred Treatment with Curative Intent for Localised Prostate Cancer from an International Collaborative Study (DETECTIVE Study).

BACKGROUND: There is uncertainty in deferred active treatment (DAT) programmes, regarding patient selection, follow-up and monitoring, reclassification, and which outcome measures should be prioritised. OBJECTIVE: To develop consensus statements for all domains of DAT. DESIGN, SETTING, AND PARTICIPANTS: A protocol-driven, three phase study was undertaken by the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Association of Urology Section of Urological Research (ESUR)-International Society of Geriatric Oncology (SIOG) Prostate Cancer Guideline Panel in conjunction with partner organisations, including the following: (1) a systematic review to describe heterogeneity across all domains; (2) a two-round Delphi survey involving a large, international panel of stakeholders, including healthcare practitioners (HCPs) and patients; and (3) a consensus group meeting attended by stakeholder group representatives. Robust methods regarding what constituted the consensus were strictly followed. RESULTS AND LIMITATIONS: A total of 109 HCPs and 16 patients completed both survey rounds. Of 129 statements in the survey, consensus was achieved in 66 (51%); the rest of the statements were discussed and voted on in the consensus meeting by 32 HCPs and three patients, where consensus was achieved in additional 27 statements (43%). Overall, 93 statements (72%) achieved consensus in the project. Some uncertainties remained regarding clinically important thresholds for disease extent on biopsy in low-risk disease, and the role of multiparametric magnetic resonance imaging in determining disease stage and aggressiveness as a criterion for inclusion and exclusion. CONCLUSIONS: Consensus statements and the findings are expected to guide and inform routine clinical practice and research, until higher levels of evidence emerge through prospective comparative studies and clinical trials. PATIENT SUMMARY: We undertook a project aimed at standardising the elements of practice in active surveillance programmes for early localised prostate cancer because currently there is great variation and uncertainty regarding how best to conduct them. The project involved large numbers of healthcare practitioners and patients using a survey and face-to-face meeting, in order to achieve agreement (ie, consensus) regarding best practice, which will provide guidance to clinicians and researchers.

Clinical response to radium-223 dichloride in men with metastatic castrate-resistant prostate cancer.

PURPOSE/OBJECTIVE: Radium-223 prolongs survival and decreases symptomatic skeletal events in men with metastatic castrate-resistant prostate cancer and is indicated in patients with painful bone metastases. However, pain responses are rarely reported and often asked about by patients. Further, patients and their physicians are concerned about a lack of pain response portending a poor treatment response and may be inclined to change systemic therapies before completing 6 cycles. We evaluated the likelihood and time course of pain response, potential predictors of response, and its prognostic value in patients receiving radium-223. MATERIALS AND METHODS: We reviewed the charts of patients who received radium-223 in our department. All patients were planned for 6 cycles with a prescribed dose of 50-55 kBq/kg at each administration. Pain scores, subjective response to pain, analgesic use, treatment toxicities, and laboratory values were recorded at each visit. Symptomatic skeletal events and survival were also recorded. RESULTS: 48 patients received at least one cycle of radium-223 and 27 (56%) received all 6 planned cycles. Median survival from first treatment was 16.0 months (95% CI 8.9 to 19.2 months). 33% experienced at least one symptomatic skeletal event during or after treatment. 62.5% of men reported a decrease in pain from pre-treatment baseline. Of men with improved pain, 96% experienced an improvement before the third cycle. Pain relief was not associated with a decrease in ALK-P or PSA or improved survival. CONCLUSIONS: Approximately two-thirds of patients who undergo treatment with radium-223 will experience an improvement in pain and, if it occurs, it will most likely occur within the first two cycles. Patients should be counseled about this timeline and, if pain improvement isn't achieved, palliative radiation and oral analgesic readjustment should be considered. Pain response is not associated with survival and should not be used to evaluate the effectiveness of treatment.

Impact of increasing margin around the lumpectomy cavity to define the planning target volume for 3D conformal external beam accelerated partial breast irradiation.

The purpose of this study was to evaluate the dose to normal tissues as a function of increasing margins around the lumpectomy cavity in accelerated partial breast irradiation (APBI) using 3D-conformal radiotherapy (3DCRT). Eight patients with Stage 0-I breast cancer underwent treatment planning for 3DCRT APBI. The clinical target volume (CTV) was defined as a 15-mm expansion around the cavity limited by the chest wall and skin. Three planning target volumes (PTV1, PTV2, PTV3) were generated for each patient using a 0, 5-, and 10-mm expansion around the CTV, for a total margin of 15, 20, and 25 mm. Three treatment plans were generated for every patient using the 3 PTVs, and dose-volume analysis was performed for each plan. For each 5-mm increase in margin, the mean PTV:total breast volume ratio increased 10% and the relative increase in the mean ipsilateral breast dose was 15%. The mean volume of ipsilateral breast tissue receiving 75%, 50%, and 25% of the prescribed dose increased 6% to 7% for every 5 mm increase in PTV margin. Compared to lesions located in the upper outer quadrant, plans for medially located tumors revealed higher mean ipsilateral breast doses and 20% to 22% more ipsilateral breast tissue encompassed by the 25% IDL. The use of 3DCRT for APBI delivers higher doses to normal breast tissue as the PTV increases around the lumpectomy cavity. Efforts should be made to minimize the overall PTV when this technique is used. Ongoing studies will be necessary to determine the clinical relevance of these findings.

A Detailed Dosimetric Analysis of Spinal Cord Tolerance in High-Dose Spine Radiosurgery.

OBJECTIVE: Dose-volume tolerance of the spinal cord (SC) in spinal stereotactic radiosurgery (SRS) is difficult to define because radiation myelitis rates are low, and published reports document cases of myelopathy but do not account for the total number of patients treated at given dose-volume combinations who do not have myelitis. This study reports SC toxicity from single-fraction spinal SRS and presents a comprehensive atlas of the incidence of adverse events to examine dose-volume predictors. METHODS AND MATERIALS: A prospective database of all patients undergoing single-fraction spinal SRS at our institution between 2004 and 2011 was reviewed. SC toxicity was defined by clinical myelitis with accompanying magnetic resonance imaging (MRI) signal changes that were not attributable to tumor progression. Dose-volume histogram (DVH) atlases were created for these endpoints. Rates of adverse events with 95% confidence limits and probabilities that rates of adverse events were <2% and <5% for myelitis were determined as functions of dose and absolute volume. RESULTS: Information about DVH and myelitis was available for 228 patients treated at 259 sites. The median follow-up time was 14.6 months (range, 0.1-138.3 months). The median prescribed dose to the planning treatment volume was 24 Gy (range, 18-24 Gy). There were 2 cases of radiation myelitis (rate r=0.7%) with accompanying MRI signal changes. Myelitis occurred in 2 patients, with Dmax >13.33 Gy, and minimum doses to the hottest 0.1, 0.2, 0.5, and 1 cc were >10.66, 10.9, and 8 Gy, respectively; however, both myelitis cases occurred below the 34th percentile for Dmax and there were 194 DVHs in total with Dmax >13.33 Gy. CONCLUSIONS: A median SC Dmax of 13.85 Gy is safe and supports that a Dmax limit of 14 Gy carries a low <1% rate of myelopathy. No dose-volume thresholds or relationships between SC dose and myelitis were apparent. This is the largest study examining dosimetric data and radiation-induced myelitis in de novo spine SRS.

Accuracy evaluation of a six-degree-of-freedom couch using cone beam CT and IsoCal phantom with an in-house algorithm.

PURPOSE: The accuracy of a six degree of freedom (6DoF) couch was evaluated using a novel method. METHODS: Cone beam CT (CBCT) images of a 3D phantom (IsoCal) were acquired with different, known combinations of couch pitch and roll angles. Pitch and roll angles between the maximum allowable values of 357 and 3 degrees were tested in one degree increments. A total of 49 combinations were tested at 0 degrees of yaw (couch rotation angle). The 3D positions of 16 tungsten carbide ball bearings (BBs), each 4 mm in diameter and arranged in a known geometry within the IsoCal phantom, were determined in the 49 image sets with in-house software. The BB positions at different rotation angles were determined using a rotation matrix from the original BB positions at zero pitch and roll angles. A linear least squares fit method estimated the rotation angles and differences between detected and nominal rotation angles were calculated. This study was conducted for the case with and without extra weight on the couch. Couch walk shifts for the system were investigated using eight combinations of rotation, roll and pitch. RESULTS: A total of 49 CBCT images with voxel sizes 0.5 × 0.5 × 1.0 mm3 were taken for the case without extra weight on the couch. The 16 BBs were determined to evaluate the isocenter translation and rotation differences between the calculated and nominal couch values. Among all 49 calculations, the maximum rotation angle differences were 0.10 degrees for pitch, 0.15 degrees for roll and 0.09 degrees for yaw. The corresponding mean and standard deviation values were 0.028 ± 0.032, -0.043 ± 0.058, and -0.009 ± 0.033 degrees. The maximum translation differences were 0.3 mm in the left-right direction, 0.5 mm in the anterior-posterior direction and 0.4 mm in the superior-inferior direction. The mean values and corresponding standard deviations were 0.07 ± 0.12, -0.05 ± 0.25, and -0.12±0.14 mm for the planes described above. With an 80 kg phantom on the couch, the maximum translation shift was 0.69 mm. The couch walk translation shifts were less than 0.1 mm and rotation shifts were less than 0.1 degree. CONCLUSIONS: Errors of a new 6DoF couch were tested using CBCT images of a 3D phantom. The rotation errors were less than 0.3 degree and the translation errors were less than or equal to 0.8 mm in each direction. This level of accuracy is warranted for clinical radiotherapy utilization including stereotactic radiosurgery.