Target margins in radiotherapy of prostate cancer

We reviewed the literature on the use of margins in radiotherapy of patients with prostate cancer, focusing on different options for image guidance (IG) and technical issues. The search in PubMed database was limited to include studies that involved external beam radiotherapy of the intact prostate. Post-prostatectomy studies, brachytherapy and particle therapy were excluded. Each article was characterized according to the IG strategy used: positioning on external marks using room lasers, bone anatomy and soft tissue match, usage of fiducial markers, electromagnetic tracking and adapted delivery. A lack of uniformity in margin selection among institutions was evident from the review. In general, introduction of pre-and in-treatment IG was associated with smaller planning target volume (PTV) margins, but there was a lack of definitive experimental/clinical studies providing robust information on selection of exact PTV values. In addition, there is a lack of comparative research regarding the cost-benefit ratio of the different strategies: insertion of fiducial markers or electromagnetic transponders facilitates prostate gland localization but at a price of invasive procedure; frequent pretreatment imaging increases patient in-room time, dose and labour; online plan adaptation should improve radiation delivery accuracy but requires fast and precise computation. Finally, optimal protocols for quality assurance procedures need to be established

Adaptive radiotherapy planning on decreasing gross tumor volumes as seen on megavoltage computed tomography images.

PURPOSE: To evaluate gross tumor volume (GTV) changes for patients with non-small-cell lung cancer by using daily megavoltage (MV) computed tomography (CT) studies acquired before each treatment fraction on helical tomotherapy and to relate the potential benefit of adaptive image-guided radiotherapy to changes in GTV. METHODS AND MATERIALS: Seventeen patients were prescribed 30 fractions of radiotherapy on helical tomotherapy for non-small-cell lung cancer at London Regional Cancer Program from Dec 2005 to March 2007. The GTV was contoured on the daily MVCT studies of each patient. Adapted plans were created using merged MVCT-kilovoltage CT image sets to investigate the advantages of replanning for patients with differing GTV regression characteristics. RESULTS: Average GTV change observed over 30 fractions was -38%, ranging from -12 to -87%. No significant correlation was observed between GTV change and patient\u27s physical or tumor features. Patterns of GTV changes in the 17 patients could be divided broadly into three groups with distinctive potential for benefit from adaptive planning. CONCLUSIONS: Changes in GTV are difficult to predict quantitatively based on patient or tumor characteristics. If changes occur, there are points in time during the treatment course when it may be appropriate to adapt the plan to improve sparing of normal tissues. If GTV decreases by greater than 30% at any point in the first 20 fractions of treatment, adaptive planning is appropriate to further improve the therapeutic ratio

Dosimetric Evaluation of PSMA PET-Delineated Dominant Intraprostatic Lesion Simultaneous Infield Boosts

Purpose: Prostate cancer is multifocal. However, there often exists a single dominant focus in the gland responsible for driving the biology of the disease. Dose escalation to the dominant lesion is a proposed strategy to increase tumor control. We applied radiobiological modeling to evaluate the dosimetric feasibility and benefit of dominant intraprostatic lesion simultaneous in-field boosts (DIL-SIB) to the gross tumor volume (GTV), defined using a novel molecular positron emission tomography (PET) probe (18F-DCFPyL) directed against prostate specific membrane antigen (PSMA). Methods and Materials: Patients with clinically localized, biopsy-proven prostate cancer underwent preoperative [ F]-DCFPyL PET/computed tomography (CT). DIL-SIB plans were generated by importing the PET/CT into the RayStation treatment planning system. GTV-PET for the DIL-SIB was defined by the highest %SUVmax (percentage of maximum standardized uptake value) that generated a biologically plausible volume. Volumetric arc–based plans incorporating prostate plus DIL-SIB treatment were generated. Tumor control probability (TCP) and normal tissue complication probability (NTCP) with fractionation schemes and boost doses specified in the FLAME (Investigate the Benefit of a Focal Lesion Ablative Microboost in Prostate Cancer; NCT01168479), PROFIT (Prostate Fractionated Irradiation Trial; NCT00304759), PACE (Prostate Advances in Comparative Evidence; NCT01584258), and hypoFLAME (Hypofractionated Focal Lesion Ablative Microboost in prostatE Cancer 2.0; NCT02853110) protocols were compared. Results: Comparative DIL-SIB plans for 6 men were generated from preoperative [ F]-DCFPyL PET/CT. Median boost GTV volume was 1.015 cm (0.42-1.83 cm ). Median minimum (D99%) DIL-SIB dose for F35 , F20 , F5 , and F5 were 97.3 Gy, 80.8 Gy, 46.5 Gy, and 51.5Gy. TCP within the GTV ranged from 84% to 88% for the standard plan and 95% to 96% for the DIL-SIB plans. Within the rest of the prostate, TCP ranged from 89% to 91% for the standard plans and 90% to 92% for the DIL-SIB plans. NTCP for the rectum NTCP was similar for the DIL-SIB plans (0.3%-2.7%) compared with standard plans (0.7%-2.6%). Overall, DIL-SIB plans yielded higher uncomplicated TCP (NTCP, 90%-94%) versus standard plans (NTCP, 83%-85%). Conclusions: PSMA PET provides a novel approach to define GTV for SIB-DIL dose escalation. Work is ongoing to validate PSMA PET-delineated GTV through correlation to coregistered postprostatectomy digitized histopathology. 18 18 3 3 BS BS BS BS

\u3csup\u3e68\u3c/sup\u3e Ga-Labeled Prostate-specific Membrane Antigen Ligand Positron Emission Tomography/Computed Tomography for Prostate Cancer: A Systematic Review and Meta-analysis

Context: Gallium prostate-specific membrane antigen (PSMA) ligand Ga-HBED-CC-PSMA ( Ga-PSMA) is a promising radiotracer for positron emission tomography (PET)/computed tomography (CT) of prostate cancer. Objective: To conduct a meta-analysis to evaluate detection rate, diagnostic test accuracy, and adverse effects of Ga-PSMA PET/CT or PET/magnetic resonance imaging (MRI) for staging of prostate cancer and for restaging of rising prostate-specific antigen (PSA) after initial treatment. Evidence acquisition: Following the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines, our systematic review searched for articles in PubMed and EMBASE databases from 2012 to July 2016. The reference standard was pathology after biopsy or surgery. The analyses used a random effect model and a hierarchical summary receiver operating characteristic model. Evidence synthesis: Fifteen Ga-PSMA PET/CT studies with 1256 patients met the inclusion criteria. Seven studies of staging PET/CT or PET/MRI detected a regional site of cancer for 203 of 273 patients (74%). Nine studies of restaging PET/CT detected sites of recurrence in 799 of 983 patients (81%) with a 50% detection rate (74 of 147 patients) for restaging PSA of 0.2–0.49 ng/ml and a 53% detection rate (56 of 195 patients) for restaging PSA of 0.50–0.99 ng/ml. Staging Ga-PSMA PET/CT in the studies had higher detection rates of sites in the prostate bed than restaging Ga-PSMA PET/CT (mean 57% vs 14%, p = 0.031, t test). Both staging and restaging Ga-PSMA PET/CT found that a subgroup of the patients had metastatic sites in pelvic lymph nodes or distant organs. Eight studies of staging PET/CT undertook histologic correlations. We performed prostate-segment-based analysis specifically regarding the primary cancer lesion for four of these studies, and patient-based analysis specifically regarding pelvic lymph node metastases for four other studies. The pooled sensitivities for staging in the two groups of studies were 70% and 61%, and the pooled specificities were 84% and 97%. None of the studies reported complications from the PET/CT imaging. Conclusions: Ga-PSMA PET/CT has clinical relevance to detect sites of recurrence for patients with PSA recurrence after radical prostatectomy (RP) with PSA levels less than 1.0 ng/ml. Patient summary: Choline positron emission tomography (PET)/computed tomography (CT) can detect sites of recurrent prostate cancer in an earlier phase of prostate-specific antigen (PSA) recurrence than bone scans and CT scans, but choline PET/CT is rarely positive for patients with restaging PSA levels under 1 ng/ml. A new radiotracer called Ga-PSMA for PET/CT was able to detect sites of recurring cancer in up to 50% of patients who had an early rise in PSA exceeding 0.5 ng/ml after initial radical prostatectomy. The published studies did not report adverse effects of Ga-PSMA PET/CT imaging. The rate of detection of sites in the prostate bed was significantly higher for staging than for restaging positron emission tomography (PET) using a Ga-labeled prostate-specific membrane (PSMA) antigen ligand. Overall, the detection rate did not differ significantly between staging and restaging. The detection rate for restaging Ga-PSMA PET/computed tomography (CT) was 50% for restaging prostate-specific antigen (PSA) of 0.2–0.48 ng/ml, 53% for restaging PSA of 0.50–0.99 ng/ml, and higher for higher restaging PSA levels. Patient-based and lesion-based analysis of staging Ga-PSMA PET/CT had sensitivity of 61–70% and specificity of 84–97%. The studies did not report any adverse effects due to imaging. 68 68 68 68 68 68 68 68 68 68 68 68 68 6

Hypofractionated stereotactic radiotherapy for intracranial meningioma: A systematic review

Background: The availability of image guidance and intensity modulation has led to the increasing use of hypofractionated stereotactic radiotherapy (hSRT) as an alternative to conventionally fractionated radiotherapy or radiosurgery for intracranial meningiomas (ICMs). As the safety and efficacy of this approach is not well characterized, we conducted a systematic review of the literature to assess the clinical outcomes of hSRT in the setting of ICMs. Methods: A systematic review of Medline and EMBASE databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Included studies were retrospective or prospective series that examined an ICM population of ≥10 patients, delivered \u3e1 fraction of photon hSRT (≥2.5 Gy per fraction), and had a median follow-up of ≥2 years. Descriptive statistics were generated for included studies. Results: Of 1480 initial studies, 14 met eligibility criteria for inclusion, reporting on 630 patients (age range, 18-90) treated for 638 tumors. Primary radiotherapy was delivered in 37% of patients, 36% had radiation following surgery, and surgical details were unavailable for 27%. In 474 tumors assessed for radiologic response, 78% remained stable, 18% decreased in size, and 4% increased in size. Crude local control was 90%-100% as reported in 10 studies. The median late toxicity rate was 10%. The most common significant late toxicities were decreased visual acuity and new cranial neuropathy. Conclusions: With limited follow-up, the available literature suggests hSRT for ICMs has local control and toxicity profiles comparable to other radiotherapy approaches. Confirmation in larger patient cohorts with a longer duration of follow-up is required

Dynamic perfusion CT in brain tumors.

Dynamic perfusion CT (PCT) is an imaging technique for assessing the vascular supply and hemodynamics of brain tumors by measuring blood flow, blood volume, and permeability-surface area product. These PCT parameters provide information complementary to histopathologic assessments and have been used for grading brain tumors, distinguishing high-grade gliomas from other brain lesions, differentiating true progression from post-treatment effects, and predicting prognosis after treatments. In this review, the basic principles of PCT are described, and applications of PCT of brain tumors are discussed. The advantages and current challenges, along with possible solutions, of PCT are presented

A Phase I/II Trial of Fairly Brief Androgen Suppression and Stereotactic Radiation Therapy for High-Risk Prostate Cancer (FASTR-2): Preliminary Results and Toxicity Analysis

Purpose: FASTR was designed to provide a compact treatment course for high-risk prostate cancer patients but was discontinued because of excess toxicity. We present the results of FASTR-2, which used a lower dose to the prostate (35 Gy vs 40 Gy), smaller posterior PTV margin (4 mm vs 5 mm) and omitted nodal radiation to lower the volumes of rectum receiving high and intermediate doses compared with FASTR. Gastrointestinal (GI) and genitourinary (GU) toxicities at baseline, 6 weeks, 6 months, and 1 year and biochemical control rates are presented. Methods and Materials: Eligibility included high-risk prostate cancer (cT3/4, prostate-specific antigen \u3e20 or Gleason Score ≥8), age ≥70 or refused standard treatment, and no evidence of metastatic disease. Patients received 18 months of androgen deprivation therapy starting 2 months before radiation. Clinical target volume was defined as prostate plus proximal 1-cm seminal vesicles. PTV was a nonuniform expansion around clinical target volume (4 mm posteriorly, 5 mm in all other directions). Volumetric arc therapy was used for treatment delivery (35 Gy delivered in 5 weekly fractions of 7 Gy each), and cone beam computed tomography with soft tissue matching (no fiducial placement) was used for daily image guidance. Toxicity was assessed at 6 weeks, 6 months, and 1 year according to Common Toxicity Criteria. Results: In the study, 30 patients were enrolled in FASTR-2 between 2015 and 2017. Two patients were withdrawn owing to ineligibility after enrollment. One patient (3.7%) reported grade 2 GI toxicity at 6 weeks. There was no reported grade ≥2 GI toxicity at 6 months or 1 year. There were no reported episodes of rectal bleeding. Four patients (14.8%), 5 patients (17.9%), and 5 patients (21.7%) reported grade 2 GU toxicity at 6 weeks, 6 months, and 1 year, respectively. There were no reported cases of grade ≥3 GU toxicity. The most common toxicities were nocturia and urinary frequency or urgency. Conclusions: FASTR-2 was more tolerable than FASTR, with no grade ≥3 toxicities reported, in keeping with expectations based on our previous FASTR analysis. Long-term follow-up is necessary to ensure disease control and toxicity outcomes are comparable to conventional high-risk treatment paradigms