Influence of respiratory motion management technique on radiation pneumonitis risk with robotic stereotactic body radiation therapy.

PURPOSE/OBJECTIVES: For lung stereotactic body radiation therapy (SBRT), real-time tumor tracking (RTT) allows for less radiation to normal lung compared to the internal target volume (ITV) method of respiratory motion management. To quantify the advantage of RTT, we examined the difference in radiation pneumonitis risk between these two techniques using a normal tissue complication probability (NTCP) model. MATERIALS/METHOD: 20 lung SBRT treatment plans using RTT were replanned with the ITV method using respiratory motion information from a 4D-CT image acquired at the original simulation. Risk of symptomatic radiation pneumonitis was calculated for both plans using a previously derived NTCP model. Features available before treatment planning that identified significant increase in NTCP with ITV versus RTT plans were identified. RESULTS: Prescription dose to the planning target volume (PTV) ranged from 22 to 60 Gy in 1-5 fractions. The median tumor diameter was 3.5 cm (range 2.1-5.5 cm) with a median volume of 14.5 mL (range 3.6-59.9 mL). The median increase in PTV volume from RTT to ITV plans was 17.1 mL (range 3.5-72.4 mL), and the median increase in PTV/lung volume ratio was 0.46% (range 0.13-1.98%). Mean lung dose and percentage dose-volumes were significantly higher in ITV plans at all levels tested. The median NTCP was 5.1% for RTT plans and 8.9% for ITV plans, with a median difference of 1.9% (range 0.4-25.5%, pairwise P < 0.001). Increases in NTCP between plans were best predicted by increases in PTV volume and PTV/lung volume ratio. CONCLUSIONS: The use of RTT decreased the risk of radiation pneumonitis in all plans. However, for most patients the risk reduction was minimal. Differences in plan PTV volume and PTV/lung volume ratio may identify patients who would benefit from RTT technique before completing treatment planning.

A multi-institutional comparison of outcomes of immunosuppressed and immunocompetent patients treated with surgery and radiation therapy for cutaneous squamous cell carcinoma of the head and neck.

BACKGROUND: Patients who are chronically immunosuppressed have higher rates of cutaneous squamous cell carcinoma of the head and neck (cSCC-HN). This is the largest multi-institutional study to date investigating the effect of immune status on disease outcomes in patients with cSCC-HN who underwent surgery and received postoperative radiation therapy (RT). METHODS: Patients from 3 institutions who underwent surgery and also received postoperative RT for primary or recurrent, stage I through IV cSCC-HN between 1995 and 2015 were included in this institutional review board-approved study. Patients categorized as immunosuppressed had chronic hematologic malignancy, human immunodeficiency/acquired immunodeficiency syndrome, or had received immunosuppressive therapy for organ transplantation ≥6 months before diagnosis. Overall survival, locoregional recurrence-free survival, and progression-free survival were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed using Cox proportional-hazards regression. RESULTS: Of 205 patients, 138 (67.3%) were immunocompetent, and 67 (32.7%) were immunosuppressed. Locoregional recurrence-free survival (47.3% vs 86.1%; P < .0001) and progression-free survival (38.7% vs 71.6%; P = .002) were significantly lower in immunosuppressed patients at 2 years. The 2-year OS rate in immunosuppressed patients demonstrated a similar trend (60.9% vs 78.1%; P = .135) but did not meet significance. On multivariate analysis, immunosuppressed status (hazard ratio [HR], 3.79; P < .0001), recurrent disease (HR, 2.67; P = .001), poor differentiation (HR, 2.08; P = .006), and perineural invasion (HR, 2.05; P = .009) were significantly associated with locoregional recurrence. CONCLUSIONS: Immunosuppressed patients with cSCC-HN had dramatically lower outcomes compared with immunocompetent patients, despite receiving bimodality therapy. Immune status is a strong prognostic factor that should be accounted for in prognostic systems, treatment algorithms, and clinical trial design. Cancer 2017;123:2054-2060. © 2017 American Cancer Society.

Long-Term Update of NRG/RTOG 0522: A Randomized Phase 3 Trial of Concurrent Radiation and Cisplatin With or Without Cetuximab in Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The combination of cisplatin and radiation or cetuximab and radiation improves overall survival of patients with locoregionally advanced head and neck carcinoma. NRG Oncology conducted a phase 3 trial to test the hypothesis that adding cetuximab to radiation and cisplatin would improve progression-free survival (PFS). METHODS AND MATERIALS: Eligible patients with American Joint Committee on Cancer sixth edition stage T2 N2a-3 M0 or T3-4 N0-3 M0 were accrued from November 2005 to March 2009 and randomized to receive radiation and cisplatin without (arm A) or with (arm B) cetuximab. Outcomes were correlated with patient and tumor features. Late reactions were scored using Common Terminology Criteria for Adverse Events (version 3). RESULTS: Of 891 analyzed patients, 452 with a median follow-up of 10.1 years were alive at analysis. The addition of cetuximab did not improve PFS (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.89-1.26; P = .74), with 10-year estimates of 43.6% (95% CI, 38.8- 48.4) for arm A and 40.2% (95% CI, 35.4-45.0) for arm B. Cetuximab did not reduce locoregional failure (HR, 1.21; 95% CI, 0.95-1.53; P = .94) or distant metastasis (HR, 0.79; 95% CI, 0.54-1.14; P = .10) or improve overall survival (HR, 0.97; 95% CI, 0.80-1.16; P = .36). Cetuximab did not appear to improve PFS in either p16-positive oropharynx (HR, 1.30; 95% CI, 0.87-1.93) or p16-negative oropharynx or nonoropharyngeal primary (HR, 0.94; 95% CI, 0.73-1.21). Grade 3 to 4 late toxicity rates were 57.4% in arm A and 61.3% in arm B (P = .26). CONCLUSIONS: With a median follow-up of more than 10 years, this updated report confirms the addition of cetuximab to radiation therapy and cisplatin did not improve any measured outcome in the entire cohort or when stratifying by p16 status.

Radiation Therapy for Brain Metastases: A Systematic Review.

PURPOSE: This evidence report synthesizes the available evidence on radiation therapy for brain metastases. METHODS AND MATERIALS: The literature search included PubMed, EMBASE, Web of Science, Scopus, CINAHL, clinicaltrials.gov, and published guidelines in July 2020; independently submitted data, expert consultation, and contacting authors. Included studies were randomized controlled trials (RCTs) and large observational studies (for safety assessments), evaluating whole brain radiation therapy (WBRT) and stereotactic radiosurgery (SRS) alone or in combination, as initial or postoperative treatment, with or without systemic therapy for adults with brain metastases due to lung cancer, breast cancer, or melanoma. RESULTS: Ninety-seven studies reported in 189 publications were identified, but the number of analyses was limited owing to different intervention and comparator combinations as well as insufficient reporting of outcome data. Risk of bias varied, and 25 trials were terminated early, predominantly owing to poor accrual. The combination of SRS plus WBRT compared with SRS alone or WBRT alone showed no statistically significant difference in overall survival (hazard ratio [HR], 1.09; 95% confidence interval [CI], 0.69%-1.73%; 4 RCTs) or death owing to brain metastases (relative risk [RR], 0.93; 95% CI, 0.48%-1.81%; 3 RCTs). Radiation therapy after surgery did not improve overall survival compared with surgery alone (HR, 0.98; 95% CI, 0.76%-1.26%; 5 RCTs). Data for quality of life, functional status, and cognitive effects were insufficient to determine effects of WBRT, SRS, or postsurgery interventions. We did not find systematic differences across interventions in serious adverse events, number of adverse events, radiation necrosis, fatigue, or seizures. WBRT plus systemic therapy (RR 1.44; 95% CI, 1.03%-2.00%; 14 studies) was associated with increased risks for vomiting compared with WBRT alone. CONCLUSIONS: Despite the substantial research literature on radiation therapy, comparative effectiveness information is limited. There is a need for more data on patient-relevant outcomes such as quality of life, functional status, and cognitive effects.

Use of Salvage Surgery or Stereotactic Radiosurgery for Multiply Recurrent Skull Base Chordomas: A Single-Institution Experience and Review of the Literature.

Introduction Chordomas are locally destructive neoplasms characterized by appreciable recurrence rates after initial multimodality treatment. We examined the outcome of salvage treatment in recurrent/progressive skull base chordomas. Methods This is a retrospective review of recurrent/progressive skull base chordomas at a tertiary urban academic medical center. The outcomes evaluated were overall survival, progression-free survival (PFS), and incidence of new toxicity. Results Eighteen consecutive patients who underwent ≥1 course of treatment (35.3% salvage surgery, 23.5% salvage radiation, and 41.2% both) were included. The median follow-up was 98.6 months (range 16-215 months). After initial treatment, the median PFS was 17.7 months (95% confidence interval [CI]: 4.9-22.6 months). Following initial therapy, age ≥ 40 had improved PFS on univariate analysis ( p = 0.03). All patients had local recurrence, with 15 undergoing salvage surgical resections and 16 undergoing salvage radiation treatments (mostly stereotactic radiosurgery [SRS]). The median PFS was 59.2 months (95% CI: 4.0-99.3 months) after salvage surgery, 58.4 months (95% CI: 25.9-195 months) after salvage radiation, and 58.4 months (95% CI: 25.9.0-98.4 months) combined. Overall survival for the total cohort was 98.7% ± 1.7% at 2 years and 92.8% ± 5.5% at 5 years. Salvage treatments were well-tolerated with two patients (11%) reporting tinnitus and one patient each (6%) reporting headaches, visual field deficits, hearing loss, anosmia, dysphagia, or memory loss. Conclusion Refractory skull base chordomas present a challenging treatment dilemma. Repeat surgical resection or SRS seems to provide adequate salvage therapy that is well-tolerated when treated at a tertiary center offering multimodality care.

Dural recurrence among esthesioneuroblastoma patients presenting with intracranial extension.

OBJECTIVE: To quantify the rate of late intracranial recurrences among esthesioneuroblastoma patients treated with surgical resection and postoperative radiation. STUDY DESIGN: Retrospective review. METHODS: All patients receiving definitive-intent therapy for esthesioneuroblastoma between March 1995 and September 2015 were reviewed. Presenting disease extent was categorized based on radiologic, operative, and pathologic findings. Between-group survival differences were assessed using Kaplan-Meier method and log-rank test. Multivariate analyses were performed using Cox proportional hazards model. RESULTS: Of 38 patients initially treated at our institution, 53% (20 of 38) presented with intracranial extension. At a median follow-up of 90 months (range, 6-199), 37% (14 of 38) recurred; 5- and 8-year disease-free survival rates were 69% and 54%; and overall survival rates were 81% and 72%, respectively. Among these patients, the dura was the most commonly involved site of relapse (8), followed by local (6), regional (5), and distant extracranial (3) sites; and five patients had ≥ two categories of failure. Eight-year dural disease-free survival was 57% versus 90% (P = 0.017) and 0% versus 87% (P < 0.0001), with and without intracranial extension and subtotal resection, respectively. Of six patients treated at recurrence, five (83%) experienced dural-based failure such that, among all 44 patients, 13 (65%) of 20 recurrences involved the dura. After dural recurrence, the median survival time was 42 months (range, 12-125); salvage treatments were effective in rare cases of isolated low-volume recurrence. CONCLUSION: Esthesioneuroblastoma patients presenting with intracranial extension are at substantial and unique risk for long-term dural-based relapse. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:2226-2233, 2018.

Pretreatment metabolic tumor volume as a prognostic factor in HPV-associated oropharyngeal cancer in the context of AJCC 8th edition staging.

BACKGROUND: This study evaluates the prognostic significance of 18 F-fluorodeoxyglucose-positron emission tomography ([F-18]FDG-PET)-derived metabolic tumor volume (MTV) in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinomas (OPSCCs) in the context of AJCC 8th edition staging. METHODS: We performed a retrospective study of HPV-associated OPSCCs treated with postoperative or definitive radiation. The prognostic significance of pretreatment MTV for freedom from recurrence (FFR), freedom from distant metastasis (FFDM), and overall survival (OS) was determined using Kaplan-Meier analysis. Multivariate analysis (MVA) was performed using Cox regression. RESULTS: In this 153-patient cohort, stratifying by the optimum MTV (24 cm3 ) was prognostic for FFR (P = .0002), FFDM (P = .001), and OS (P < .0001). Metabolic tumor volume (MTV) was prognostic of FFR in AJCC 8th edition stage I/II (P = .03), and stage III patients (P = .04). On multivariate analysis only MTV was a significant factor for OS. CONCLUSION: Metabolic tumor volume (MTV) is a significant prognostic factor in HPV-associated OPSCCs, independent of AJCC 8th edition stage.

Squamous cell carcinoma of unknown primary of the head and neck: Favorable prognostic factors comparable to those in oropharyngeal cancer.

BACKGROUND: Treatment for squamous cell carcinoma (SCC) of unknown primary consists of radiotherapy (RT) +/- chemotherapy or neck dissection +/- adjuvant RT/chemoradiotherapy (CRT). We compared these strategies and identified prognostic factors. METHODS: From 1993 to 2015, 75 patients with SCC of unknown primary had RT-based or surgery-based treatment. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Event-time distributions were estimated using the Kaplan-Meier method. RESULTS: Five-year OS and DFS for RT-based and surgery-based treatments were similar (OS 73% vs 68%, respectively; DFS 65% vs 64%, respectively). Among 38 patients with p16 data, 76% were p16 positive and showed improved 5-year DFS (90% vs 33%; P = .001) and OS (96% vs 33%; P < .001). Smoking history ≤10 pack-years conferred better 5-year DFS (88% vs 49%; P < .001) and OS (91% vs 59%; P < .001). CONCLUSION: RT-based and surgery-based treatments produced similar outcomes. Patients with p16-positive disease with ≤10 pack-years of smoking history and limited nodal stage constitute a "low-risk" group in SCC of unknown primary similar to that in oropharyngeal cancer.

Major prognostic factors for recurrence and survival independent of the American Joint Committee on Cancer eighth edition staging system in patients with cutaneous squamous cell carcinoma treated with multimodality therapy.

BACKGROUND: The purpose of this study was to assess changes resulting from the American Joint Committee on Cancer (AJCC) eighth edition for cutaneous squamous cell carcinoma (SCC) and evaluate pertinent excluded factors. METHODS: In 101 patients receiving surgery and postoperative radiation, recurrence and survival were estimated by cumulative incidence and Kaplan-Meier method. Time-to-event analysis was performed using Cox proportional hazards and Fine-Gray competing risks regression models. RESULTS: The 2-year locoregional recurrence, overall survival (OS), and cause-specific mortality rates were 25%, 72%, and 13%, respectively. The AJCC eighth edition upstaged T classification in 50% of patients and overall stage in 39%. In multivariate analysis, immunosuppression and in-transit metastasis were associated with locoregional recurrence. Older age and in-transit metastasis were associated with worse OS. In univariate analysis (limited by number of events), cause-specific mortality was associated with positive margin, in-transit metastasis, and the seventh edition dichotomized T classification and overall stage. CONCLUSION: In-transit metastasis was significantly associated with locoregional recurrence, OS, and cause-specific mortality. Efforts should be made to define in-transit metastasis in the staging system.

Internal dose escalation is associated with increased local control for non-small cell lung cancer (NSCLC) brain metastases treated with stereotactic radiosurgery (SRS).

OBJECTIVE: To identify potentially actionable dosimetric predictors of local control (LC) for non-small cell lung cancer (NSCLC) brain metastases treated with single-fraction stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Patients with NSCLC brain metastases treated with single-fraction SRS were identified. Eligible patients had at least 1 follow-up magnetic resonance imaging scan and were without prior metastasectomy or SRS to the same lesion. LC and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate (UVA) and multivariate analysis (MVA). Receiver operating characteristic (ROC) analysis was used to identify optimal cut points for dose-volume histogram metrics relative to LC. RESULTS: A total of 612 NSCLC brain metastasis were identified in 299 patients with single-fraction SRS between 1999 and 2014. Median follow-up was 10 months. Median OS from time of SRS was 11 months. Overall LC was 75% and 66% at 1 and 2 years, respectively. On UVA, increasing dose by any measure was associated with improved LC. On MVA, volume receiving at least 32 Gy (V32; hazard ratio [HR], 0.069; P < .000), along with higher prescription isodose (HR, 0.953; P = .031) and lower volume (HR, 1.359; P < .000), were independent predictors of improved LC. ROC analysis demonstrated a V32 of 24% to be most predictive for LC. For the entire cohort, 1-year LC for V32 ≥24% was 89% versus 67% for V32 <24% (P = .000). Stratifying by volume, lesions ≤2 cm (n = 323) had a 1-year LC of 95% versus 82% (P = .005) for V32 above and below 24%, respectively. For lesions 2.1 to 3 cm (n = 211), 1-year LC was 79% versus 59% (P = .003) for V32 above and below 24%, respectively. Total tumor volume alone was predictive for OS. CONCLUSIONS: Volume, prescription isodose line, and V32 are independent predictors of LC. V32 represents an actionable SRS treatment planning parameter for NSCLC brain metastases.

Management of Chordoma and Chondrosarcoma with Fractionated Stereotactic Radiotherapy.

OBJECTIVE: To evaluate the efficacy and toxicity of fractionated stereotactic radiotherapy (FSRT) for chordoma and chondrosarcoma. METHODS: Twenty consecutive patients with a histopathologic diagnosis of chordoma (n = 16) or chondrosarcoma (n = 4) treated between 2010 and 2016 were retrospectively identified. All patients underwent FSRT in five fractions to a median dose of 37.5 Gy (range: 25-40 Gy) and followed with serial magnetic resonance imaging. Overall survival (OS), local recurrence-free survival (LRFS), and event-free survival (EFS) were estimated using the Kaplan-Meier method. RESULTS: With a median follow-up of 28 months after FSRT and 40 months after initial surgery, crude OS and LRFS were 90%. Nine patients (45%) reported grade 1-3 acute toxicity, and two patients (10%) experienced grade 4, 5 late toxicity. One patient previously treated with proton therapy died from radiation vasculopathy 9 months after FSRT. The use of FSRT for recurrent disease or in patients with prior radiation therapy was associated with significantly decreased EFS. CONCLUSION: FSRT for chordoma and chondrosarcoma is associated with high rates of OS and local control. Although many patients experience acute toxicity, there is a low incidence of late toxicity or irreversible treatment related morbidity despite the frequency of prior radiotherapy in this population. FSRT is an effective adjuvant or salvage treatment for chordoma and chondrosarcoma.

Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel.

PURPOSE: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). EXPERIMENTAL DESIGN: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with one-way ANOVA. RESULTS: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C>T variants were 0.7%, 9.2%, 2.1%, 0.5%, 93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C>T variant and any of the studied pharmacokinetic variables. CONCLUSIONS: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics.

Does radiation dose matter in thyroid cancer?: Patterns of local-regional failure in recurrent and metastatic well-differentiated thyroid cancers treated with dose-painted intensity-modulated radiation therapy.

INTRODUCTION: Due to complex multimodal treatments and a lengthy natural history of disease, the impact of radiation therapy for well-differentiated thyroid cancer (WDTC) is challenging to evaluate. We analysed the effect of dose escalation, as enabled by intensity-modulated radiation therapy (IMRT), on preventing local-regional failure (LRF) of microscopic and macroscopic WDTC. METHOD: We performed a retrospective review of WDTC patients treated with IMRT from 1998-2011. Diagnostic imaging demonstrating first LRF was registered to the simulation CT containing the treated radiation isodose volumes. Areas of disease progression were contoured and the relationships of LRFs with isodose volumes were recorded. RESULTS: Thirty patients had a median follow-up of 56 months (range = 1-139). Seventeen (57%) had gross residual, five (17%) had microscopic residual and eight (27%) had clear margins at the time of IMRT. Nine patients (30%) developed LRF, at a median time of 44 months (range = 0-116). Of these, six (67%) had been radiated to gross disease and one (11%) had microscopic residual. In the seven analysable cases, only one (14%) LRF occurred within the 70 Gy isodose volume. Marginal LRFs were: four (57%) outside 70 Gy, one (14%) outside 60 Gy and one (14%) outside 50 Gy. All but one recurrence (86%) occurred in the perioesophageal region. CONCLUSIONS: Local-regional failure was seen most in patients who had gross disease at the time of IMRT, almost always occurred outside of the 70 Gy volume and was frequently in the area of oesophageal sparing. Meticulous surgical dissection, especially in the perioesophageal region, should be prioritised to prevent long-term LRF.

CYP3A4 and CYP3A5 genotyping by Pyrosequencing.

BACKGROUND: Human cytochrome P450 3A enzymes, particularly CYP3A4 and CYP3A5, play an important role in drug metabolism. CYP3A expression exhibits substantial interindividual variation, much of which may result from genetic variation. This study describes Pyrosequencing assays for key SNPs in CYP3A4 (CYP3A4*1B, CYP3A4*2, and CYP3A4*3) and CYP3A5 (CYP3A5*3C and CYP3A5*6). METHODS: Genotyping of 95 healthy European and 95 healthy African volunteers was performed using Pyrosequencing. Linkage disequilibrium, haplotype inference, Hardy-Weinberg equilibrium, and tag SNPs were also determined for these samples. RESULTS: CYP3A4*1B allele frequencies were 4% in Europeans and 82% in Africans. The CYP3A4*2 allele was found in neither population sample. CYP3A4*3 had an allele frequency of 2% in Europeans and 0% in Africans. The frequency of CYP3A5*3C was 94% in Europeans and 12% in Africans. No CYP3A5*6 variants were found in the European samples, but this allele had a frequency of 16% in the African samples. Allele frequencies and haplotypes show interethnic variation, highlighting the need to analyze clinically relevant SNPs and haplotypes in a variety of ethnic groups. CONCLUSION: Pyrosequencing is a versatile technique that could improve the efficiency of SNP analysis for pharmacogenomic research with the ultimate goal of pre-screening patients for individual therapy selection.

Pyrosequencing of clinically relevant polymorphisms.

The data generated from the Human Genome Project has led to an explosion of technology for low-, medium-, and high-throughput genotyping methods. Pyrosequencing is a genotyping assay based on sequencing by synthesis. Short runs of sequence around each polymorphism are generated, allowing for internal controls for each sample. Pyrosequencing can also be used to identify tri-allelic, indel, and short-repeat polymorphisms, as well as determining allele percentages for methylation or pooled sample assessment. Assays details for Pyrosequencing of clinically relevant polymorphisms are described in this chapter.

Transperineal ultrasound-guided implantation of electromagnetic transponders in the prostatic fossa for localization and tracking during external beam radiation therapy.

PURPOSE: To describe a transperineal ultrasound-guided technique for implantation of electromagnetic transponders into the prostatic fossa. METHODS AND MATERIALS: Patients were placed in the dorsal lithotomy position, and local anesthetic was administered. On ultrasound, the bladder, urethra, vesicourethral anastomosis, rectum, and the prostatic fossa were carefully identified. Three transponders were implanted into the prostatic fossa under ultrasound guidance in a triangular configuration and implantation was verified by fluoroscopy. Patients underwent computed tomography (CT) simulation approximately 1 week later. All patients in this study were subsequently treated with intensity modulated radiation therapy (IMRT) to the prostatic fossa. RESULTS: From 2008 to 2012, 180 patients received transperineal implantation of electromagnetic transponders into the prostatic fossa and subsequently received IMRT. There were no cases of severe hematuria or rectal bleeding requiring intervention. There were no grade 3 or 4 toxicities. Three patients (1.7%) had a transponder missing on the subsequent CT simulation. Thirteen patients (7.3%) had transponder migration with a geometric residual that exceeded 2 mm for 3 consecutive days (5.6%) or rotation that exceeded 10 degrees for 5 consecutive days (1.7%). These patients underwent a resimulation CT scan to identify the new transponder coordinates. CONCLUSIONS: A transperineal technique for implantation of electromagnetic transponders into the prostatic fossa is safe and well tolerated, with no severe toxicity after implantation. There is a low rate of transponder loss or migration.

Outcomes of iodine-125 plaque brachytherapy for uveal melanoma with intraoperative ultrasonography and supplemental transpupillary thermotherapy.

PURPOSE: To assess the impact on local tumor control of intraoperative ultrasonographic plaque visualization and selective application of transpupillary thermotherapy (TTT) in the treatment of posterior uveal melanoma with iodine-125 (I-125) episcleral plaque brachytherapy (EPB). METHODS AND MATERIALS: Retrospective analysis of 526 patients treated with I-125 EPB for posterior uveal melanoma. Clinical features, dosimetric parameters, TTT treatments, and local tumor control outcomes were recorded. Statistical analysis was performed using Cox proportional hazards and Kaplan-Meier life table method. RESULTS: The study included 270 men (51%) and 256 women (49%), with a median age of 63 years (mean, 62 years; range, 16-91 years). Median dose to the tumor apex was 94.4 Gy (mean, 97.8; range, 43.9-183.9) and to the tumor base was 257.9 Gy (mean, 275.6; range, 124.2-729.8). Plaque tilt >1 mm away from the sclera at plaque removal was detected in 142 cases (27%). Supplemental TTT was performed in 72 patients (13.7%). One or 2 TTT sessions were required in 71 TTT cases (98.6%). After a median follow-up of 45.9 months (mean, 53.4 months; range, 6-175 months), local tumor recurrence was detected in 19 patients (3.6%). Local tumor recurrence was associated with lower dose to the tumor base (P=.02). CONCLUSIONS: Ultrasound-guided plaque localization of I-125 EPB is associated with excellent local tumor control. Detection of plaque tilt by ultrasonography at plaque removal allows supplemental TTT to be used in patients at potentially higher risk for local recurrence while sparing the majority of patients who are at low risk. Most patients require only 1 or 2 TTT sessions.

Predictors of individual tumor local control after stereotactic radiosurgery for non-small cell lung cancer brain metastases.

PURPOSE: To evaluate local control rates and predictors of individual tumor local control for brain metastases from non-small cell lung cancer (NSCLC) treated with stereotactic radiosurgery (SRS). METHODS AND MATERIALS: Between June 1998 and May 2011, 401 brain metastases in 228 patients were treated with Gamma Knife single-fraction SRS. Local failure was defined as an increase in lesion size after SRS. Local control was estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis. Receiver operating characteristic analysis was used to identify an optimal cutpoint for conformality index relative to local control. A P value <.05 was considered statistically significant. RESULTS: Median age was 60 years (range, 27-84 years). There were 66 cerebellar metastases (16%) and 335 supratentorial metastases (84%). The median prescription dose was 20 Gy (range, 14-24 Gy). Median overall survival from time of SRS was 12.1 months. The estimated local control at 12 months was 74%. On multivariate analysis, cerebellar location (hazard ratio [HR] 1.94, P=.009), larger tumor volume (HR 1.09, P<.001), and lower conformality (HR 0.700, P=.044) were significant independent predictors of local failure. Conformality index cutpoints of 1.4-1.9 were predictive of local control, whereas a cutpoint of 1.75 was the most predictive (P=.001). The adjusted Kaplan-Meier 1-year local control for conformality index ≥ 1.75 was 84% versus 69% for conformality index <1.75, controlling for tumor volume and location. The 1-year adjusted local control for cerebellar lesions was 60%, compared with 77% for supratentorial lesions, controlling for tumor volume and conformality index. CONCLUSIONS: Cerebellar tumor location, lower conformality index, and larger tumor volume were significant independent predictors of local failure after SRS for brain metastases from NSCLC. These results warrant further investigation in a prospective setting.

Stereotactic body radiation therapy for the treatment of early-stage minimally invasive adenocarcinoma or adenocarcnioma in situ (formerly bronchioloalveolar carcinoma): a patterns of failure analysis.

INTRODUCTION: Ongoing prospective trials exploring stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) often exclude minimally invasive adenocarcinoma or adenocarcnioma in situ, formerly bronchioloalveolar carcinoma (BAC), due to concerns for accurate target delineation on CT. We performed a patterns of failure analysis to compare outcomes between BAC and other NSCLC subtypes. METHODS: One hundred twenty patients with early stage NSCLC were treated with SBRT from 2004-2009. Pathologic confirmation of NSCLC was obtained in 97 patients. Radiotherapy was delivered according to RTOG guidelines. The log-rank test was used to compare outcomes between BAC and other NSCLC. RESULTS: Median follow-up was 29 months. The median SBRT dose was 5400 cGy. Thirteen patients had radiographically diagnosed BAC and five patients had biopsy confirmed BAC, of which two had both. The three-year local control was 100% for biopsy-proven or radiographically diagnosed BAC (n = 18) and 86% for all other NSCLC subtypes (n = 102) (p = 0.13). Likewise, no significant difference was detected between BAC and other NSCLC for 3-year regional failure (12% vs. 20%, p = 0.45), progression-free survival (57.6% vs. 53.5%, p = 0.84) or overall survival (35% vs. 47%, p = 0.66). There was a trend towards lower three-year rates of freedom from distant failure in patients with any diagnosis of BAC compared to those without (26% vs. 38%, p = 0.053). CONCLUSIONS: Compared to other NSCLC subtypes, BAC appears to have similar patterns of failure and survival after treatment with SBRT, however there may be an increased risk of distant metastases with BAC. RTOG guideline-based target delineation provides encouraging local control rates for patients with BAC.