Stereotactic ablative radiotherapy for operable stage I non-small-cell lung cancer (revised STARS): long-term results of a single-arm, prospective trial with prespecified comparison to surgery.

BACKGROUND: A previous pooled analysis of the STARS and ROSEL trials showed higher survival after stereotactic ablative radiotherapy (SABR) than with surgery for operable early-stage non-small-cell lung cancer (NSCLC), but that analysis had notable limitations. This study reports long-term results of the revised STARS trial, in which the SABR group was re-accrued with a larger sample size, along with a protocol-specified propensity-matched comparison with a prospectively registered, contemporary institutional cohort of patients who underwent video-assisted thoracoscopic surgical lobectomy with mediastinal lymph node dissection (VATS L-MLND). METHODS: This single-arm prospective trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA) and enrolled patients aged 18 years or older with a Zubrod performance status of 0-2, newly diagnosed and histologically confirmed NSCLC with N0M0 disease (squamous cell, adenocarcinoma, large cell, or NSCLC not otherwise specified), and a tumour diameter of 3 cm or less. This trial did not include patients from the previous pooled analysis. SABR dosing was 54 Gy in three fractions (for peripheral lesions) or 50 Gy in four fractions (for central tumours; simultaneous integrated boost to gross tumour totalling 60 Gy). The primary endpoint was the 3-year overall survival. For the propensity-matching analysis, we used a surgical cohort from the MD Anderson Department of Thoracic and Cardiovascular Surgery's prospectively registered, institutional review board-approved database of all patients with clinical stage I NSCLC who underwent VATS L-MLND during the period of enrolment in this trial. Non-inferiority could be claimed if the 3-year overall survival rate after SABR was lower than that after VATS L-MLND by 12% or less and the upper bound of the 95% CI of the hazard ratio (HR) was less than 1·965. Propensity matching consisted of determining a propensity score using a multivariable logistic regression model including several covariates (age, tumour size, histology, performance status, and the interaction of age and sex); based on the propensity scores, one patient in the SABR group was randomly matched with one patient in the VATS L-MLND group using a 5:1 digit greedy match algorithm. This study is registered with ClinicalTrials.gov, NCT02357992. FINDINGS: Between Sept 1, 2015, and Jan 31, 2017, 80 patients were enrolled and included in efficacy and safety analyses. Median follow-up time was 5·1 years (IQR 3·9-5·8). Overall survival was 91% (95% CI 85-98) at 3 years and 87% (79-95) at 5 years. SABR was tolerated well, with no grade 4-5 toxicity and one (1%) case each of grade 3 dyspnoea, grade 2 pneumonitis, and grade 2 lung fibrosis. No serious adverse events were recorded. Overall survival in the propensity-matched VATS L-MLND cohort was 91% (95% CI 85-98) at 3 years and 84% (76-93) at 5 years. Non-inferiority was claimed since the 3-year overall survival after SABR was not lower than that observed in the VATS L-MLND group. There was no significant difference in overall survival between the two patient cohorts (hazard ratio 0·86 [95% CI 0·45-1·65], p=0·65) from a multivariable analysis. INTERPRETATION: Long-term survival after SABR is non-inferior to VATS L-MLND for operable stage IA NSCLC. SABR remains promising for such cases but multidisciplinary management is strongly recommended. FUNDING: Varian Medical Systems and US National Cancer Institute (National Institutes of Health).

Prospective trial of regional (hockey-stick) prostate cryoablation: oncologic and quality of life outcomes.

PURPOSE: To report long-term follow-up of the efficacy of subtotal prostate ablation using a "hockey-stick" template, including oncologic control and quality of life (QoL) impact. METHODS: We performed a prospective controlled trial to evaluate the efficacy of subtotal prostate ablation in selected men with baseline and confirmatory biopsy showing grade group (GG) 1-2 prostate cancer. "Hockey-stick" cryoablation that included the ipsilateral hemi-gland and contralateral anterior prostate was performed. Prostate biopsies and QOL queries were performed at 6, 18 and 36 months following regional ablation, and follow-up was updated to include subsequent clinic visits. RESULTS: Between August 2009 and January 2012, 72 men were screened for eligibility and 47 opted to undergo confirmatory biopsy. Of these, 23 were deemed eligible and treated with regional cryoablation. Median age was 64 years. Median follow-up was 74 months. A single patient had < 1 mm of in-field viable tumor with therapy effect on 36-month biopsy. At time of last follow-up, a total of 12/23 (52%) patients did not have evidence of disease, all patients had preserved urinary control with no patients requiring pads for urinary incontinence. Sexual decline was significant at 3 and 6 months (P < 0.01 for both), though improvement was seen at subsequent time points. CONCLUSION: Subtotal (hockey-stick template) cryoablation of the prostate provides oncologic control to targeted tissue in a generally low-risk group with minimal impact on sexual and urinary function. Further studies are needed to evaluate this ablation template in the MRI-targeted era and higher risk populations.

Variability of the Positive Predictive Value of PI-RADS for Prostate MRI across 26 Centers: Experience of the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel.

Background Prostate MRI is used widely in clinical care for guiding tissue sampling, active surveillance, and staging. The Prostate Imaging Reporting and Data System (PI-RADS) helps provide a standardized probabilistic approach for identifying clinically significant prostate cancer. Despite widespread use, the variability in performance of prostate MRI across practices remains unknown. Purpose To estimate the positive predictive value (PPV) of PI-RADS for the detection of high-grade prostate cancer across imaging centers. Materials and Methods This retrospective cross-sectional study was compliant with the HIPAA. Twenty-six centers with members in the Society of Abdominal Radiology Prostate Cancer Disease-focused Panel submitted data from men with suspected or biopsy-proven untreated prostate cancer. MRI scans were obtained between January 2015 and April 2018. This was followed with targeted biopsy. Only men with at least one MRI lesion assigned a PI-RADS score of 2-5 were included. Outcome was prostate cancer with Gleason score (GS) greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2). A mixed-model logistic regression with institution and individuals as random effects was used to estimate overall PPVs. The variability of observed PPV of PI-RADS across imaging centers was described by using the median and interquartile range. Results The authors evaluated 3449 men (mean age, 65 years ± 8 [standard deviation]) with 5082 lesions. Biopsy results showed 1698 cancers with GS greater than or equal to 3+4 (International Society of Urological Pathology grade group ≥2) in 2082 men. Across all centers, the estimated PPV was 35% (95% confidence interval [CI]: 27%, 43%) for a PI-RADS score greater than or equal to 3 and 49% (95% CI: 40%, 58%) for a PI-RADS score greater than or equal to 4. The interquartile ranges of PPV at these same PI-RADS score thresholds were 27%-44% and 27%-48%, respectively. Conclusion The positive predictive value of the Prostate Imaging and Reporting Data System was low and varied widely across centers. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Milot in this issue.

Cost and efficacy comparison of five prostate biopsy modalities: a platform for integrating cost into novel-platform comparative research.

BACKGROUND: The cornerstone of prostate cancer diagnosis remains the transrectal ultrasound-guided biopsy (TRUS-BX), which most frequently occurs in the office setting under local anesthesia. However, there are now other techniques of prostate biopsy aimed at improving outcomes such as patient comfort, significant cancer detection, and infectious complications. The purpose of the present study is to compare the cost and efficacy outcomes of five different approaches. METHODS: We compared the comprehensive costs of a random sample size of 20-30 cases from each of the following: (1) local anesthesia TRUS-BX (reference), (2) sedation TRUS-BX, (3) general anesthesia transperineal template biopsy (TP), (4) sedation MRI-TRUS fusion biopsy (FB), and (5) sedation in-bore MRI biopsy (IB-MRI). Cost categories included pre-procedure, anesthesia pharmacy and recovery, and the technical/professional costs from urology, radiology, and pathology services. For procedure outcomes, we compared the larger cohorts of TRUS-BX, TP, and FB in terms of indication, cancer yield, and downstream decision impact. RESULTS: Compared with standard TRUS-BX, the total costs of sedation TRUS-BX, TP, FB, and IB-MRI increased significantly ×1.9 (90%), ×2.5 (153%), ×2.5 (150%), and ×2.2 (125%), respectively (p < 0.001). Although there was no statistical difference between the total costs of TP, FB, and IB-MRI, these costs were significantly higher than those of TRUS-BX under either local anesthesia or sedation (p < 0.05). The cost of TRUS-BX under sedation was significantly higher than that of TRUS-BX under local anesthesia (p < 0.001). Compared to TRUS-BX, more significant cancers were detected in FB (16% vs. 36%) and TP (16% vs. 34%) groups (p < 0.001). CONCLUSIONS: Compared with standard TRUS-BX, the additions of imaging, sedation anesthesia, and transperineal template increase costs significantly, and can be considered along with known improvements in accuracy and side effects. Ongoing efforts to combine imaging and transperineal biopsy, especially in an outpatient/local anesthesia setting may lead to a higher cost/benefit.

Efficacy of a Self-expanding Tract Sealant Device in the Reduction of Pneumothorax and Chest Tube Placement Rates After Percutaneous Lung Biopsy: A Matched Controlled Study Using Propensity Score Analysis.

PURPOSE: To evaluate the use of a self-expanding tract sealant device (BioSentry™) on the rates of pneumothorax and chest tube insertion after percutaneous lung biopsy. MATERIALS AND METHODS: In this retrospective study, we compared 318 patients who received BioSentry™ during percutaneous lung biopsy (treated group) with 1956 patients who did not (control group). Patient-, lesion-, and procedure-specific variables, and pneumothorax and chest tube insertion rates were recorded. To adjust for potential selection bias, patients in the treated group were matched 1:1 to patients in the control group using propensity score matching based on the above-mentioned variables. Patients were considered a match if the absolute difference in their propensity scores was ≤equal to 0.02. RESULTS: Before matching, the pneumothorax and chest tube rates were 24.5 and 13.1% in the control group, and 21.1 and 8.5% in the treated group, respectively. Using propensity scores, a match was found for 317 patients in the treatment group. Chi-square contingency matched pair analysis showed the treated group had significantly lower pneumothorax (20.8 vs. 32.8%; p = 0.001) and chest tube (8.2 vs. 20.8%; p < 0.0001) rates compared to the control group. Sub-analysis including only faculty who had >30 cases of both treatment and control cases demonstrated similar findings: the treated group had significantly lower pneumothorax (17.6 vs. 30.2%; p = 0.002) and chest tube (7.2 vs. 18%; p = 0.001) rates. CONCLUSIONS: The self-expanding tract sealant device significantly reduced the pneumothorax rate, and more importantly, the chest tube placement rate after percutaneous lung biopsy.

Prospective validation of treatment accuracy using implanted fiducial markers for spinal stereotactic body radiation therapy.

In order to accurately assess positioning errors in spinal SBRT, many institutions employ bony-fusion based imaging techniques, such as the ExacTrac™ (Brain Lab) system, in conjunction with 3D verification (performed via CT-on-rails in our practice). We hypothesized that the use of implanted gold fiducial markers could improve the accuracy of patient positioning over bony fusion alone. We addressed this question prospectively, enrolling patients on an IRB-approved protocol. Gold seeds were implanted in the vertebral pedicles flanking the target level. At treatment, setup error was calculated using two methods-standard kV image fusion, and geometric fiducial-based projection, with independent CT-on-rails verification. Analyses of residual set-up error showed that fiducial-based setup agreed with fusion-based determination, but did not significantly reduce error. Offline 6D fusion of the treatment and planning CT illustrated residual rotational error using standard or fiducial based setup. We conclude that the ExacTrac and CT-on-rails platform yields highly accurate results for spinal SBRT setup, with reduced residual error than previously reported. While the addition of fiducials did not further reduce error, the bony fusion approach is now prospectively validated in comparison to implanted fiducials. Both bony fusion and fiducial marker methods are associated with residual rotational error, thus 3D verification remains an important component of spinal SBRT treatment.

Stereotactic ablative radiotherapy versus lobectomy for operable stage I non-small-cell lung cancer: a pooled analysis of two randomised trials.

BACKGROUND: The standard of care for operable, stage I, non-small-cell lung cancer (NSCLC) is lobectomy with mediastinal lymph node dissection or sampling. Stereotactic ablative radiotherapy (SABR) for inoperable stage I NSCLC has shown promising results, but two independent, randomised, phase 3 trials of SABR in patients with operable stage I NSCLC (STARS and ROSEL) closed early due to slow accrual. We aimed to assess overall survival for SABR versus surgery by pooling data from these trials. METHODS: Eligible patients in the STARS and ROSEL studies were those with clinical T1-2a (<4 cm), N0M0, operable NSCLC. Patients were randomly assigned in a 1:1 ratio to SABR or lobectomy with mediastinal lymph node dissection or sampling. We did a pooled analysis in the intention-to-treat population using overall survival as the primary endpoint. Both trials are registered with ClinicalTrials.gov (STARS: NCT00840749; ROSEL: NCT00687986). FINDINGS: 58 patients were enrolled and randomly assigned (31 to SABR and 27 to surgery). Median follow-up was 40·2 months (IQR 23·0-47·3) for the SABR group and 35·4 months (18·9-40·7) for the surgery group. Six patients in the surgery group died compared with one patient in the SABR group. Estimated overall survival at 3 years was 95% (95% CI 85-100) in the SABR group compared with 79% (64-97) in the surgery group (hazard ratio [HR] 0·14 [95% CI 0·017-1·190], log-rank p=0·037). Recurrence-free survival at 3 years was 86% (95% CI 74-100) in the SABR group and 80% (65-97) in the surgery group (HR 0·69 [95% CI 0·21-2·29], log-rank p=0·54). In the surgery group, one patient had regional nodal recurrence and two had distant metastases; in the SABR group, one patient had local recurrence, four had regional nodal recurrence, and one had distant metastases. Three (10%) patients in the SABR group had grade 3 treatment-related adverse events (three [10%] chest wall pain, two [6%] dyspnoea or cough, and one [3%] fatigue and rib fracture). No patients given SABR had grade 4 events or treatment-related death. In the surgery group, one (4%) patient died of surgical complications and 12 (44%) patients had grade 3-4 treatment-related adverse events. Grade 3 events occurring in more than one patient in the surgery group were dyspnoea (four [15%] patients), chest pain (four [15%] patients), and lung infections (two [7%]). INTERPRETATION: SABR could be an option for treating operable stage I NSCLC. Because of the small patient sample size and short follow-up, additional randomised studies comparing SABR with surgery in operable patients are warranted. FUNDING: Accuray Inc, Netherlands Organisation for Health Research and Development, NCI Cancer Center Support, NCI Clinical and Translational Science Award.

Phase I clinical trial of hepatic arterial infusion of paclitaxel in patients with advanced cancer and dominant liver involvement.

PURPOSE: The survival of patients with liver metastases from solid tumors is poor. We conducted a phase I study of hepatic arterial infusion (HAI) paclitaxel in patients with advanced cancer and predominant liver involvement. METHODS: Patients were treated with HAI paclitaxel 150-275 mg/m(2) (and 15,000 IU heparin intraarterially) every 28 days. A "3 + 3" study design was used. RESULTS: Twenty-six patients were treated (median age, 59 years). Diagnoses were colorectal cancer (n = 10), breast cancer (n = 7), and other (n = 9). The median number of prior therapies was four (range, 0-10). The maximum tolerated dose (MTD) was HAI paclitaxel 225 mg/m(2). Dose-limiting toxicities (DLTs) included Grade 3 neuropathy (1 of 5 patients) at HAI paclitaxel 275 mg/m(2) and Grade 4 thrombocytopenia and neutropenia, and Grade 3 mucositis (1 of 4 patients) at 250 mg/m(2). None of the eight patients treated with HAI paclitaxel 225 mg/m(2) experienced a DLT. The most common toxicities were nausea and peripheral neuropathy. Of 22 patients evaluable for response, 3 (13.6%) patients had SD for ≥4 months (colorectal cancer, n = 1; thyroid cancer, n = 1; and hepatocellular carcinoma, n = 1; duration of response was 4 months, 7.1 months, and 22.2+ months, respectively). CONCLUSION: The MTD of HAI paclitaxel was 225 mg/m(2). This regimen was well tolerated and had antitumor activity in selected patients.

Impact of C-arm CT on hepatic arterial interventions for hepatic malignancies.

PURPOSE: To evaluate C-arm computed tomography (CT) and assess its potential impact on hepatic arterial interventions. MATERIALS AND METHODS: Between May 2005 and March 2006, all hepatic arterial interventions for hepatic malignancies were retrospectively reviewed. C-arm CT acquisitions were performed as an adjunct to conventional digital subtraction angiography (DSA). The number of procedures with C-arm CT, the acquisitions per intervention, and the procedure time for all interventions were recorded. The added information provided by C-arm CT was scored as category 1 (no additional information); category 2 (added information without impact on procedure management); or category 3 (added information with impact on procedure management). Intervention types included infusions, radioembolization, embolization, and chemoembolization. A two-sided, two-sample t test was used to compare interventions with and without C-arm CT, and P values less than .05 were considered significant. RESULTS: C-arm CT was used in 86 of 240 interventions (36%) in 135 patients. The mean number of acquisitions per study was 1.9 (range, 1-4). Thirty-five interventions (40.7%) were scored as category 2 and 16 interventions (18.6%) were scored as category 3. Chemoembolization was associated with the highest percentage of C-arm CT investigations classified as category 2 and 3 assessed per intervention. The mean procedure time was significantly longer (18 minutes) when C-arm CT was used (P<.001). CONCLUSIONS: C-arm CT provides additional imaging information beyond DSA during hepatic arterial interventions (approximately 60%), and this information impacted procedure management in 19% of cases. C-arm CT offers the greatest opportunity for additional information during chemoembolization procedures and is responsible for a significant but acceptable increase in procedure time for this type of hepatic intervention.

Hepatic artery chemoembolization for 110 gastrointestinal stromal tumors: response, survival, and prognostic factors.

BACKGROUND: The efficacy of hepatic artery chemoembolization (HACE) was evaluated for gastrointestinal stromal tumors (GISTs) metastatic to the liver. METHODS: Records for patients with metastatic GIST who underwent HACE between January 1993 and March 2005 were reviewed and cross-sectional images were used to determine objective tumor response. Progression-free survival in the liver (PFS-liver) and overall survival (OS) were calculated with the Kaplan-Meier method. Patient, tumor, and treatment variables were analyzed to identify factors influencing survival. RESULTS: Of the 110 patients identified, the radiologic response to HACE could be evaluated in 85 patients, 12 of whom (14%) demonstrated partial responses, 63 of whom (74%) demonstrated stable disease, and 10 of whom (12%) demonstrated progressive disease. PFS-liver rates were 31.2%, 8.2%, and 5.4% at 1, 2, and 3 years, respectively; the median PFS time was 8.2 months. OS rates were 62% at 1 year, 32% at 2 years, and 20% at 3 years; the median OS time was 17.2 months. Patients who had >5 liver metastases and received only 1 HACE treatment were found to have a shorter PFS compared with patients with fewer metastases or those who received > or =2 HACE sessions. Extensive liver involvement, the presence of extrahepatic metastases, and progression of liver disease after HACE were associated with poor OS. Use of imatinib prolonged OS time. CONCLUSIONS: HACE produced a durable tumor response or disease stabilization in the majority of patients with GISTs metastatic to liver. Extent of liver disease, presence of extrahepatic disease, number of embolization treatments, and use of imatinib were found to have prognostic influence on PFS, OS, or both.

Hepatic arterial embolization and chemoembolization for the treatment of patients with metastatic neuroendocrine tumors: variables affecting response rates and survival.

BACKGROUND: The objective of this study was to determine the prognostic variables that influence response and survival in patients with metastatic neuroendocrine tumors who are treated with hepatic arterial embolization (HAE) or chemoembolization (HACE). METHODS: Patients with metastatic neuroendocrine tumors who underwent HAE or HACE were included in this retrospective study. Follow-up imaging studies were compared with baseline imaging to determine the radiologic response. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Univariate and multivariate analyses were performed to assess the prognostic variables that affected response and survival. RESULTS: The study included 69 patients with carcinoid tumors and 54 patients with pancreatic islet cell carcinomas. Patients who had carcinoid tumors had a higher response rate (66.7% vs. 35.2%; P = 0.0001) and had longer PFS (22.7 mos vs. 16.1 mos; P = 0.046) and OS (33.8 mos vs. 23.2 mos; P = 0.012) compared with patients who had islet cell carcinomas. For patients with carcinoid tumors, multivariate analysis identified male gender as the only independent risk factor for poor survival (P = 0.05). Octreotide was predictive marginally for PFS (P = 0.06). Patients who were treated with HAE had a higher response rate than patients who were treated with HACE (P = 0.004). For patients with islet cell carcinoma, an intact primary tumor, > or = 75% liver involvement, and extrahepatic metastases were associated with reduced OS in the univariate analysis; the presence of bone metastases was the only risk factor (P = 0.031) in the multivariate analysis. Patients who were treated with HACE had a prolonged OS (31.5 mos vs. 18.2 mos) and improved response (50% vs. 25%) compared with patients who were treated with HAE, although the differences did not reach statistical significance. CONCLUSIONS: Patients with carcinoid tumors had better outcomes than patients with islet cell carcinomas. The addition of intraarterial chemotherapy to HAE did not improve the outcome of patients with carcinoid tumors, but it seemed to benefit patients with islet cell carcinomas. In patients who had carcinoid tumors, male gender predicted a poor outcome, and a trend toward prolonged PFS was observed in patients who received concomitant octreotide. An intact primary tumor, extensive liver disease, and bone metastases were associated with reduced survival in patients with islet cell carcinomas.

Percutaneous ultrasound-guided biopsy in the definitive diagnosis of osteosarcoma.

Thirty-three patients with 35 bone lesions suspicious for osteosarcoma underwent image-guided biopsy. Of those 35 biopsies, 12 were performed with use of fluoroscopy or computed tomography (CT) guidance to target the osseous abnormality. Diagnostic magnetic resonance imaging revealed a soft tissue component in 23 cases; in these cases, biopsies were performed with use of ultrasonography (US) to target the soft tissue component of the tumor. Of the 35 tumors in which biopsy was performed, 33 (94%) were definitively diagnosed as osteosarcoma by image-guided biopsy. All 23 US-guided biopsies resulted in definitive diagnosis. Two of the 12 fluoroscopy- or CT-guided biopsies (17%) were inconclusive.