MR signature matching (MRSIGMA) implementation for true real-time free-breathing volumetric imaging with sub-200 ms latency on an MR-Linac.

PURPOSE: Develop a true real-time implementation of MR signature matching (MRSIGMA) for free-breathing 3D MRI with sub-200 ms latency on the Elekta Unity 1.5T MR-Linac. METHODS: MRSIGMA was implemented on an external computer with a network connection to the MR-Linac. Stack-of-stars with partial kz sampling was used to accelerate data acquisition and ReconSocket was employed for simultaneous data transmission. Movienet network computed the 4D MRI motion dictionary and correlation analysis was used for signature matching. A programmable 4D MRI phantom was utilized to evaluate MRSIGMA with respect to a ground-truth translational motion reference. In vivo validation was performed on patients with pancreatic cancer, where 15 patients were employed to train Movienet and 7 patients to test the real-time implementation of MRSIGMA. Dice coefficients between real-time MRSIGMA and a retrospectively computed 4D reference were used to evaluate motion tracking performance. RESULTS: Motion dictionary was computed in under 5 s. Signature acquisition and matching presented 173 ms latency on the phantom and 193 ms on patients. MRSIGMA presented a mean error of 1.3-1.6 mm for all phantom experiments, which was below the 2 mm acquisition resolution along the motion direction. The Dice coefficient over time between MRSIGMA and reference contours was 0.88 ± 0.02 (GTV), 0.87 ± 0.02(duodenum-stomach), and 0.78 ± 0.02(small bowel), demonstrating high motion tracking performance for both tumor and organs at risk. CONCLUSION: The real-time implementation of MRSIGMA enabled true real-time free-breathing 3D MRI with sub-200 ms imaging latency on a clinical MR-Linac system, which can be used for treatment monitoring, adaptive radiotherapy and dose accumulation mapping in tumors affected by respiratory motion.

A prospective evaluation of whole brain volume loss and neurocognitive decline following hippocampal-sparing prophylactic cranial irradiation for limited-stage small-cell lung cancer.

INTRODUCTION: This study evaluated an association between whole brain volume loss and neurocognitive decline following prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (SCLC). METHODS: This was a secondary analysis of a prospective clinical trial that accrued patients at a single institution from 2013 to 2016. Patients with limited-stage SCLC treated with standard chemo-radiation received PCI 25 Gy/10 fractions, with mean hippocampal dose limited to < 8 Gy. Whole brain volumes were measured using MR imaging obtained before and at 6, 12, 18, and 24 months after PCI. Verbal memory was measured by the Hopkins Verbal Learning Test-Revised (HVLT-R) before and at 6 and 12 months after PCI. Univariate and multivariate linear regression evaluated associations between changes in whole brain volume and verbal memory. RESULTS: Twenty-two patients enrolled. The median whole brain volume before PCI was 1301 mL. Subsequent reduction in whole brain volume was greatest at 18 months after PCI (median change - 23 mL, range - 142 to 20, p = 0.03). At 6 months after PCI, reduction in volume was independently associated with decline in verbal memory, measured by two components of the HVLT-R (Delayed Recall: 0.06/mL volume change, p = 0.046; Percent Retained: 0.66/mL volume change, p = 0.030), when controlling for education and global cognitive function at baseline. CONCLUSION: This is the first study to correlate reduction in whole brain volume and decline in neurocognitive function following whole brain radiation therapy (WBRT). This suggests that loss of brain volume after WBRT may be clinically significant and subsequently impact cognition and quality of life.

Central Acetabular Impingement Is Associated With Femoral Head and Ligamentum Teres Damage: A Cross-Sectional Matched-Pair Analysis of Patients Undergoing Hip Arthroscopy for Acetabular Labral Tears.

PURPOSE: The primary purpose of this study was to report the prevalence of femoral head articular damage in patients with a central acetabular osteophyte (CAO) that was identified during hip arthroscopy and compare it with that in a matched control group without a CAO. A secondary purpose was to identify rates of coexisting intra-articular pathology in both patient groups. METHODS: Intraoperative data were collected prospectively on all hip arthroscopy patients at our institution between 2008 and 2015. The inclusion criteria for this study were CAOs identified during hip arthroscopy for a labral tear and/or femoroacetabular impingement. The exclusion criteria were Tönnis grade greater than 0, previous hip conditions, and prior surgical interventions. The matched control group was selected based on sex, age ± 5 years, body mass index, and Workers' Compensation claim at a 3:1 ratio and comprised patients who underwent hip arthroscopy for a labral tear and/or femoroacetabular impingement without a CAO. The size and location of labral tears and chondral lesions were recorded in square millimeters with a 5-mm probe and by the clock-face method. RESULTS: The CAO group consisted of 126 patients, who were matched to 378 patients in the control group. Femoral and acetabular chondral damage grades were significantly different between the 2 groups (P < .001). Of patients with CAOs, 55% had femoral head chondral damage compared with 24% of the control patients. The mean size of femoral chondral damage was 3.2 cm2 in the CAO group and 1.7 cm2 in the control group. The mean size of acetabular chondral damage was 1.7 cm2 in the CAO group and 1.2 cm2 in the control group. Both femoral and acetabular chondral damage sizes were significantly larger in the CAO group (P ≤ .007). The prevalence of ligamentum teres tears was significantly different between the 2 groups (P < .001). There were no statistically significant differences in the types of labral tears between the 2 groups (P = .625). CONCLUSIONS: This study showed that patients with CAOs had a significantly higher prevalence of femoral chondral damage and ligamentum teres tears than matched controls. LEVEL OF EVIDENCE: Level III, comparative study.

Can Stem Version Consistently Correct Native Femoral Version Using Robotic Guidance in Total Hip Arthroplasty?

The purpose of this study is to investigate whether robotic guidance in total hip arthroplasty (THA) can consistently correct native femoral version. One hundred seventy-five consecutive patients who underwent MAKO® (Stryker, Kalamazoo, Michigan) robotic-guidance THA were included in the study. The study population had a mean age of 57.9 years and a mean body mass index (BMI) of 30.41. Forty-eight percent of the population was male and 74% of the procedures were performed through an anterior approach. Robotic guidance in THA was effective in correcting native femoral version toward a target of 15°. This can be achieved using both the anterior and posterior approach; it is not affected by BMI.

Observation of nonreciprocal transmission in binary phase-shift keying modulation using traveling-wave Mach-Zehnder modulators.

In coherent optical transmission, traveling-wave Mach-Zehnder modulators are commonly used to generate various advanced formats where the modulators are biased at the minimum transmission point. Here, we report that an optical isolation effect with lower backward transmission occurs under this condition. This concept is successfully demonstrated to achieve ∼7 dB isolation over a 90-nm wavelength span under binary phase-shift keying modulation using a commercial lithium niobate modulator.

Coplanar-waveguide-based silicon Mach-Zehnder modulator using a meandering optical waveguide and alternating-side PN junction loading.

We demonstrate a silicon Mach-Zehnder modulator with a coplanar waveguide transmission-line electrode structure using a meandering optical waveguide and alternating-side PN junction loading of the electrodes, which helps suppress the signal distortion caused by the parasitic slot-line mode and improves the electro-optic (EO) bandwidth. The silicon MZM exhibits a π-phase-shift voltage (Vπ) of 4.5 V with an EO 3 dB bandwidth of ∼20 GHz for a 5 mm long phase shifter. This achieved Vπ is among the lowest for silicon-only modulators with a bandwidth of more than 20 GHz.

Arthroscopic Central Acetabular Decompression: Clinical Outcomes at Minimum 2-Year Follow-up Using a Matched-Pair Analysis.

PURPOSE: To assess 2-year clinical outcomes of patients who underwent hip arthroscopy for central acetabular osteophytes (CAO) treated with central acetabular decompression (CAD), and to compare these outcomes with those of a matched control group. METHODS: Data were prospectively gathered for patients undergoing CAD during hip arthroscopy from February 2008 to July 2012. All patients were assessed pre- and postoperatively at 3 months, 1 year, and 2 years with modified Harris Hip Score, Non-Arthritic Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, and visual analog scale (VAS) for pain. Patient satisfaction (0 to 10) was collected. A matched control group of patients without CAOs who did not undergo CAD was selected on a 1:3 ratio. RESULTS: Forty-nine hips were included in the CAD group and 147 in the control group. The mean change in patient-reported outcome (PRO) scores at 2-year follow-up in the CAD group for modified Harris Hip Score, Hip Outcome Score-Activities of Daily Living, Hip Outcome Score-Sport-Specific Subscale, Non-Arthritic Hip Score, and VAS was 11.0, 19.6, 15.2, 21.4, and -2, respectively. The mean change in PRO scores at 2-year follow-up in the control group was 17.0, 19.8, 24.0, 20.9, and -2.75, respectively. All improvements in PRO scores for both groups were statistically significant compared with the data collected preoperatively (P < .001). There was no statistically significant difference in postoperative PRO scores and VAS between the groups. Postoperative patient satisfaction at the latest follow-up was 7.14 and 7.60 for CAD and control groups, respectively. CONCLUSIONS: This study showed that patients with a CAO treated with CAD during hip arthroscopy had favorable outcomes at minimum 2 years postoperatively. Furthermore, the study group showed similar PRO scores and VAS to the control group. We conclude that CAD is a viable treatment option for CAO, yielding clinical improvement at short-term follow-up. LEVEL OF EVIDENCE: Level III, prospective comparative study.

Open and Arthroscopic Treatment of Adult Hip Dysplasia: A Systematic Review.

PURPOSE: To compare patient-reported outcome (PRO) and rates of conversion to total hip arthroplasty (THA) after hip arthroscopy, Bernese periacetabular osteotomy (PAO), and a combined approach for the management of patients with different grades of hip dysplasia. METHODS: We searched MEDLINE and PubMed databases for articles published since 2000 using the following terms: (((("hip dysplasia") or "dysplastic") and "arthroscopy")) or ((("hip dysplasia") or "dysplastic") and "osteotomy"). Two authors independently reviewed the literature. Inclusion criteria were English language, relevance to hip dysplasia, surgical outcomes, and sample size of 10 patients or more. We excluded articles that were reviews or techniques; articles that included overlapping populations, patients with a mean age less than 18 years, patients with other hip conditions, patients with genetic or neuromuscular causes of hip dysplasia, and patients with Tonnis grade 2 or greater arthritis; articles on femoral osteotomy, and articles on previous surgical intervention, except hip arthroscopy. Articles were analyzed for PRO scores and rates of conversion to THA. RESULTS: Ten of 759 articles reviewed met the inclusion and exclusion criteria. Of 834 hips treated for dysplasia with a mean age of 31 years, 114 were treated with arthroscopy alone, 703 were treated with PAO alone, and 17 were treated with both procedures. Mean follow-up was 3.2 years, 6.5 years, and 5.6 years, respectively. Conversion rates to THA were 4.8%, 12.0%, and 17.7%, respectively. In studies reporting pre- and postoperative PRO scores, all but one reported improvement. CONCLUSIONS: The management of hip dysplasia may entail hip arthroscopy, PAO, or a combined approach. Arthroscopy has resulted in improved outcomes in borderline dysplastic cases (lateral center edge angle between 18° and 25°). PAO has primarily been used in true dysplasia with continued success. There were too few combined procedures of arthroscopy with PAO to reach a reliable conclusion in this subgroup.

Demonstration of terabit-scale data transmission in silicon vertical slot waveguides.

We design and fabricate silicon vertical slot waveguides for terabit-scale data transmission. The designed silicon photonic device is composed of apodized grating couplers, strip waveguides, strip-to-slot/slot-to-strip mode converters, and slot waveguide. Tight light confinement in the nano-scale air slot region is achieved in the silicon vertical slot waveguide which features relatively lower nonlinearity compared to silicon strip waveguide. Using the fabricated silicon photonic devices, we first demonstrate ultra-wide bandwidth 1.8-Tbit/s data transmission through a 2-mm-long silicon vertical slot waveguide using 161 wavelength-division multiplexing (WDM) channels each carrying 11.2-Gbit/s orthogonal frequency-division multiplexing (OFDM) 16-ary quadrature amplitude modulation (16-QAM) signal. All 161 WDM channels achieve bit-error rate (BER) less than 1e-3 after on-chip data transmission. We further demonstrate terabit-scale data transmission through four silicon vertical slot waveguides with different lengths (1 mm, 2 mm, 3.1 mm, 12.2 mm). The optical signal-to-noise ratio (OSNR) penalties of data transmission through four silicon vertical slot waveguides are 1, 2, 3.2 and 4.5 dB at a BER of 1e-3, respectively. The obtained results indicate that the presented silicon vertical slot waveguide might be an alternative promising candidate facilitating chip-scale high-speed optical interconnections.

Experimental demonstration of analog signal transmission in a silicon photonic crystal L3 resonator.

We design and fabricate a silicon photonic crystal L3 resonator for chip-scale analog signal transmission. The lattice constant (a) is 420 nm, and the radius of holes (r) is 126 nm. The three holes adjacent to the cavity are laterally shifted by 0.175a, 0.025a and 0.175a, respectively. We experimentally evaluate the performance of silicon photonic crystal L3 resonator for chip-scale analog signal transmission. The spurious free dynamic ranges (SFDRs) of the second-order harmonic distortion (SHD) and the third-order harmonic distortion (THD), which are important factors to assess the analog link performance, are measured for the chip-scale analog signal transmission through the fabricated silicon photonic crystal L3 resonator. The SHD SFDR and THD SFDR are measured to be ~34.6 dB and ~52.2 dB even with the input optical carrier sitting at the dip resonance wavelength of the fabricated silicon photonic crystal L3 resonator. The influences of the optical carrier wavelength and input optical power on the SHD SFDR and THD SFDR are studied in the experiment. The impacts of geometric parameters of the cavity structure (lattice constant, radius of holes, shift of the hole) on the analog signal transmission are also analyzed, showing favorable analog link performance with relatively large fabrication tolerance to design parameters.

How much arthritis is too much for hip arthroscopy: a systematic review.

PURPOSE: The purpose of this study was to determine the extent of preoperative osteoarthritis (OA) that precludes benefit from hip arthroscopy by systematically reviewing the literature on hip arthroscopy in the setting of OA. METHODS: We searched the Medline and PubMed databases using the following Medical Subject Heading terms: arthritis, osteoarthritis, chondral damage, chondral injury, chondral delamination, and hip arthroscopy. Two authors independently reviewed the literature and included articles if they were in the English language; commented on preoperative factors, parameters, physical examination, or diagnostic testing that may be evidence of cartilage damage and/or arthritis; contained outcome data on patients undergoing hip arthroscopy; and had a sample size of at least 10 patients with arthritic changes in the hip. We excluded review articles, technique articles, articles with overlapping patient populations, articles with hip arthroscopy used as an adjunct to an open procedure, articles with inflammatory and septic arthritis, and articles with a mean age younger than 18 years. RESULTS: Our search identified 518 articles, of which 15 met the inclusion and exclusion criteria. Two thousand fifty-one hips underwent arthroscopy at a mean patient age of 40.2 years. Of these, 1,195 hips had signs of OA. There were 345 conversions to total hip arthroplasty/surface replacement arthroplasty. Of these patients, 274 had OA. Eight patient-reported outcome instruments were used. Factors influencing outcomes were preoperative OA, age, chondral damage, femoroacetabular impingement, and duration of symptoms. CONCLUSIONS: Current evidence is insufficient to define a cutoff for how much arthritis is too much for hip arthroscopy. However, this analysis shows that patients with a Tönnis grade of 1 or greater or a joint space of 2 mm or less are less likely to benefit from hip arthroscopy and more likely to require conversion to total hip arthroplasty/surface replacement arthroplasty. Postoperative scores on patient-reported outcome instruments are lower in the arthritic population at follow-up compared with their nonarthritic counterparts. LEVEL OF EVIDENCE: Level IV, systematic review of Level III and IV studies.

Outcomes of Open Versus Endoscopic Repair of Abductor Muscle Tears of the Hip: A Systematic Review.

PURPOSE: To compare the outcome of open versus endoscopic gluteal tendon repair. METHODS: An extensive review of PubMed was conducted by 2 independent reviewers for articles containing at least 1 of the following search terms: gluteus medius, gluteus medius tear, gluteus medius tendinopathy, gluteus medius repair, hip abductors, hip abductor tears, hip abductor repair, hip rotator cuff, hip rotator cuff repair, trochanteric bursa, trochanteric bursitis, trochanteric bursectomy, peritrochanteric procedures, peritrochanteric repair, and peritrochanteric arthroscopy. This yielded 313 articles. Of these articles, 7 satisfied the following inclusion criteria: description of an open or endoscopic gluteal repair with outcomes consisting of patient-reported outcome scores, patient satisfaction, strength scores, pain scores, and complications. RESULTS: Three studies on open gluteal repairs and 4 on endoscopic gluteal repairs met the inclusion criteria. In total, there were 127 patients who underwent open procedures and 40 patients who underwent endoscopic procedures. Of the 40 patients who underwent endoscopic procedures, 15 had concomitant intra-articular procedures documented, as compared with 0 in the open group. The modified Harris Hip Score was common to 1 study on open repairs and 3 studies on endoscopic repairs. The scores were similar for follow-up periods of 1 and 2 years. Visual analog pain scale scores were reported in 1 study on open gluteal repairs and 1 study on endoscopic repairs and were similar between the 2 studies. Improvement in abductor strength was also similarly reported in selected studies between the 2 groups. The only difference between the 2 groups was the reported incidence of complications, which was higher in the open group. CONCLUSIONS: Open and endoscopic gluteal repairs have similar patient-reported outcome scores, pain scores, and improvement in abduction strength. Open techniques have a higher reported complication rate. Randomized studies of sufficient numbers of patients are required to ultimately determine if one technique produces superior patient outcomes over the other. LEVEL OF EVIDENCE: Level IV, systematic review of Level IV studies.

Arthroscopic Treatment of Labral Tears in Patients Aged 60 Years or Older.

PURPOSE: The purpose of this study was to (1) evaluate the clinical outcomes of a series of patients aged 60 years or older who underwent hip arthroscopy for labral tears with minimum 2-year follow-up and (2) identify risk factors for conversion to total hip arthroplasty (THA). METHODS: Outcome data were prospectively collected and retrospectively reviewed in patients aged 60 years or older who underwent hip arthroscopy between April 2008 and May 2012. Four patient-reported outcome (PRO) scores, pain scores, and satisfaction ratings were collected. Conversion to THA and revision surgery rates were recorded. A subgroup analysis compared survivors with patients requiring THA. RESULTS: Minimum 2-year follow-up was available for 30 patients with a mean age of 63.9 years. The 2-year survivorship rate was 70%, with 9 patients undergoing conversion to THA at a mean of 1.1 years after hip arthroscopy. Two patients required additional surgery during the study period, for a reoperation rate of 37% (11 of 30 patients). The remaining cohort showed mean improvements in all PRO scores. All scores, except the sports-related PRO (P = .12), improved significantly from the preoperative baseline scores. Visual analog scale scores for pain decreased from a mean of 5.0 preoperatively to 2.7 postoperatively (P = .003). Patients who required conversion to THA had lower preoperative modified Harris Hip Scores (P = .015), lower preoperative Hip Outcome Score-Activity of Daily Living values (P = .01), higher pain scores (P = .05), greater acetabular inclination (P = .023), and more severe chondral damage (P = .033). CONCLUSIONS: Arthroscopic treatment of labral tears in patients aged 60 years or older should be approached with caution. Patients in this age group had an overall 2-year survivorship rate of 70% and should be counseled before surgery on the possibility of subsequent conversion to THA. Patients aged 60 years or older with poor preoperative PRO scores, high pain scores, radiographic evidence of borderline dysplasia, and severe chondral damage may be poor candidates for hip arthroscopy. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

Accuracy of Component Positioning in 1980 Total Hip Arthroplasties: A Comparative Analysis by Surgical Technique and Mode of Guidance.

The purpose of this multi-surgeon study was to assess and compare the accuracy of acetabular component placement, leg length discrepancy (LLD), and global offset difference (GOD) between six different surgical techniques and modes of guidance in total hip arthroplasty (THA). A total of 1980 THAs met inclusion criteria. Robotic- and navigation-guided techniques were more consistent than other techniques in placing the acetabular cup into Lewinnek's safe zone (P<0.005 and P<0.05, respectively). Robotic-guided surgery was more consistent than other techniques in placing the acetabular component within Callanan's safe zone (P<0.005). No statistically significant differences were found between groups in the frequency of patients with excessive LLD. Clinically significant differences between groups were not found in the frequency of patients with excessive GOD. Level of Evidence: IV.

Optical data exchange of m-QAM signals using a silicon-organic hybrid slot waveguide: proposal and simulation.

We present modulation-format-transparent data exchange for m-ary quadrature amplitude modulation (m-QAM) signals using a single silicon-organic hybrid slot waveguide which offers tight light confinement and enhanced nonlinearity. By exploiting the parametric depletion effect of non-degenerate four-wave mixing (ND-FWM) process in the slot waveguide, we simulate low-power (<10 mW) ultrahigh-speed optical data exchange of 640 Gbaud (2.56 Tbit/s) optical time-division multiplexed (OTDM) 16-QAM and 640 Gbaud (3.84 Tbit/s) OTDM 64-QAM signals and characterize the operation performance in terms of error vector magnitude (EVM) and bit-error rate (BER). The calculated signal-to-noise ratio (SNR) penalties of data exchange are negligible for 2.56 Tbit/s 16-QAM signals and less than 2 dB for 3.84 Tbit/s 64-QAM signals at a BER of 2e-3. For a given pump power of 9 mW, the operation performance dependence on the waveguide length is studied, showing an optimized waveguide length of ~17 mm. For a given waveguide length of 17 mm, the SNR penalty of data exchange, at a BER of 2e-3, is kept below 4 dB when varying input pump power from 8.4 to 9.8 mW for 2.56 Tbit/s 16-QAM and from 8.9 to 9.2 mW for 3.84 Tbit/s 64-QAM. In addition, data exchange running at low speed (e.g. 20 Gbaud) and data exchange taking into account waveguide propagation loss are also analyzed with favorable operation performance.

On-chip all-optical wavelength conversion of multicarrier, multilevel modulation (OFDM m-QAM) signals using a silicon waveguide.

We report on-chip all-optical wavelength conversion of multicarrier multilevel modulation signals in a silicon waveguide. Using orthogonal frequency-division multiplexing (OFDM) combined with advanced multilevel quadrature amplitude modulation (QAM) signals (i.e., OFDM m-QAM), we experimentally demonstrate all-optical wavelength conversions of 3.2 Gbaud/s OFDM 16/32/64/128-QAM signals based on the degenerate four-wave mixing (FWM) nonlinear effect in a silicon waveguide. The measured optical signal-to-noise ratio (OSNR) penalties of wavelength conversion are ∼3 dB for OFDM 16-QAM and ∼4 dB for OFDM 32-QAM at 7% forward error correction (FEC) threshold and ∼3.5 dB for OFDM 64-QAM and ∼4.5 dB for OFDM 128-QAM at 20% FEC threshold. The observed clear constellations of converted idlers imply favorable performance obtained for silicon-waveguide-based OFDM 16/32/64/128-QAM wavelength conversions.

Tumor Hypoxia on 18F-fluoromisonidazole Positron Emission Tomography and Distant Metastasis From Head and Neck Squamous Cell Carcinoma.

Importance: Given high rates of locoregional control after definitive management of head and neck squamous cell carcinoma (HNSCC), better methods are needed to project distant metastasis (DM) risk. Tumor hypoxia on 18F-fluoromisonidazole (FMISO) positron emission tomography (PET) is associated with locoregional failure, but data demonstrating an association with DM are limited. Objective: To determine whether tumor hypoxia on FMISO PET is associated with DM risk after chemoradiotherapy (CRT) for HNSCC. Design, Setting, and Participants: This cohort study assessed patients with HNSCC enrolled in 2 prospective clinical trials at a single academic referral center from 2004 to 2021 in which participants received FMISO PET before and during CRT. Data analysis occurred from May 2023 to May 2024. Exposures: FMISO PET scans before and 1 to 2 weeks after starting CRT were evaluated for tumor hypoxia by nuclear medicine physicians. Main Outcomes and Measures: The primary outcome was DM, defined as biopsy-proven HNSCC outside the primary site and regional lymph nodes. Time to DM was modeled with competing risk regression, with death as a competing risk. Overall survival (OS) was assessed secondarily and modeled with Cox regression. Results: Among 281 patients (median [range] age at CRT, 58.7 [25.5-85.6] years; 251 male [89.3%]) included in this study, 242 (86.1%) had oropharyngeal primary cancer, and 266 (94.7%) had human papillomavirus-positive disease. Of all patients, 217 (77.2%) had T stage 1 or 2, and 231 patients (82.2%) had N stage 2b or less. De-escalated 30 Gy CRT was delivered to 144 patients (51.2%), and the remainder received standard 70 Gy CRT. On FMISO PET examination, 73 patients (26.0%) had hypoxia-negative disease before CRT, 138 patients (49.1%) had hypoxia-positive disease before CRT and then hypoxia-negative disease during CRT, and 70 patients (24.9%) persistently had hypoxia-positive disease before and during CRT. At a median (IQR) 58 (46-91) months of follow-up, 12 DM events and 22 deaths were observed. Persistent intratreatment hypoxia was associated with increased DM risk (hazard ratio, 3.51; 95% CI, 1.05-11.79; P = .04) and worse OS (hazard ratio, 2.66; 95% CI, 1.14-6.19; P = .02). No patients with hypoxia-negative disease before CRT experienced DM. Conclusions and Relevance: In this cohort study using pooled analysis of prospective nonrandomized clinical trials incorporating FMISO PET in the definitive management of HNSCC, persistent intratreatment hypoxia was associated with increased risk of DM and worse OS. Conversely, all patients with hypoxia-negative disease before treatment remained free of DM. These findings suggest that pretreatment and intratreatment FMISO PET results may serve as biomarkers for DM risk and aid in identifying candidates for escalated therapeutic strategies.

Clinicogenomic predictors of survival and intracranial progression after stereotactic radiosurgery for colorectal cancer brain metastases.

OBJECTIVE: Brain metastases (BM) from colorectal cancer (CRC) are associated with dismal prognosis. When BM-directed therapy is considered, better methods are needed to identify patients at risk of poor oncological outcomes in order to optimize patient selection for closer surveillance or escalated therapy. The authors sought to identify clinicogenomic predictors of survival and intracranial disease progression after CRC BM have been treated with stereotactic radiosurgery (SRS). METHODS: Patients with newly diagnosed CRC BM treated with SRS between 2009 and 2022 who had next-generation genomic sequencing data available were included. Frameless SRS was delivered in 1-5 fractions, alone or after neurosurgical resection. Outcomes included overall survival (OS) and intracranial progression (IP), evaluated per patient treated with SRS, and local progression (LP), evaluated per BM. Associations between baseline clinicogenomic features and outcomes were evaluated with Cox regression and competing risk regression, with death as a competing risk. RESULTS: This analysis included 123 patients with 299 BM. At BM diagnosis, 111 patients (90%) had progressive extracranial disease, and 79 patients (64%) had ≥ 3 sites of extracranial metastasis. The median (IQR) number of BM was 2 (1-3) per patient. The median (IQR) biologically effective dose (BED) was 51.3 (51.3-65.1) Gy, corresponding to a prescription of 27 Gy in 3 fractions. OS, IP, and LP estimates at 1 year after SRS were 36%, 55%, and 12%, respectively. OS was independently associated with progressive extracranial disease (HR 4.26, 95% CI 1.63-11.2, p = 0.003) and ≥ 3 extracranial metastatic sites (HR 1.84, 95% CI 1.12-3.01, p = 0.02). LP was less likely when BM received BED ≥ 51.3 Gy (HR 0.24, 95% CI 0.07-0.78, p = 0.02), independent of BM diameter (HR 1.21/cm, 95% CI 0.8-1.84, p = 0.4). IP was independently associated with genomic alterations; TP53 driver alterations were associated with higher risk of IP (HR 2.71, 95% CI 1.26-5.79, p = 0.01), whereas MYC pathway alterations were associated with lower risk (HR 0.15, 95% CI 0.03-0.68, p = 0.01). CONCLUSIONS: The authors identified clinicogenomic features associated with adverse outcomes after SRS for CRC BM. Progressive and extensive extracranial metastases predicted worse OS. Insufficient SRS doses predicted greater risk of LP. Wild-type TP53 and alterations in the MYC pathway were independently associated with lower risk of IP. Patients at high risk of IP may be considered for closer surveillance or escalated therapy.

Deviation from consensus contouring guidelines predicts inferior local control after spine stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: To analyze the impact of target delineation on local control (LC) after stereotactic body radiotherapy (SBRT) for spine metastasis. MATERIALS AND METHODS: Patients with de novo metastasis of the spine treated with SBRT, excluding those with prostate or hematologic malignancies, were retrospectively reviewed. Deviations from consensus contouring guidelines included incomplete coverage of involved vertebral compartments, omission of adjacent compartments, or unnecessary circumferential coverage. Univariable and multivariable Cox proportional hazard analyses were performed using death as a competing risk. RESULTS: 283 patients with 360 discrete lesions were included with a median follow up of 14.6 months (range 1.2-131.3). The prescription dose was 24-27 Gy in 2-3 fractions for the majority of lesions. Median survival after SBRT was 18.3 months (95 % confidence interval [CI]: 14.8-22.8). The 1 and 2-year local control (LC) rates were 81.1 % (95 % CI: 75.5-85.6 %) and 70.6 % (95 % CI: 63.2-76.8 %), respectively. In total, 60 deviations (16.7 %) from consensus contouring guidelines were identified. Deviation from guidelines was associated with inferior LC (1-year LC 63.0 % vs 85.5 %, p < 0.001). Gastrointestinal primary, epidural extension, and paraspinal extension were all associated with inferior LC on univariable analyses. After adjusting for confounding factors, deviation from guidelines was the strongest predictor of inferior LC (HR 3.52, 95 % CI: 2.11-5.86, p < 0.001). Among guideline-compliant treatments, progressions were mainly in field (61 %) and/or epidural (49 %), while marginal (42 %) and/or epidural progressions (58 %) were most common for those with deviations. CONCLUSIONS: Adherence to consensus contouring guidelines for spine SBRT is associated with superior LC and fewer marginal misses.

Radiomic modeling to predict risk of vertebral compression fracture after stereotactic body radiation therapy for spinal metastases.

OBJECTIVE: In the treatment of spinal metastases with stereotactic body radiation therapy (SBRT), vertebral compression fracture (VCF) is a common and potentially morbid complication. Better methods to identify patients at high risk of radiation-induced VCF are needed to evaluate prophylactic measures. Radiomic features from pretreatment imaging may be employed to more accurately predict VCF. The objective of this study was to develop and evaluate a machine learning model based on clinical characteristics and radiomic features from pretreatment imaging to predict the risk of VCF after SBRT for spinal metastases. METHODS: Vertebral levels C2 through L5 containing metastases treated with SBRT were included if they were naive to prior surgery or radiation therapy, target delineation was based on consensus guidelines, and 1-year follow-up data were available. Clinical features, including characteristics of the patient, disease, and treatment, were obtained from chart review. Radiomic features were extracted from the planning target volume (PTV) on pretreatment CT and T1-weighted MRI. Clinical and radiomic features selected by least absolute shrinkage and selection operator (LASSO) regression were included in random forest classification models, which were trained to predict VCF within 1 year after SBRT. Model performance was assessed with leave-one-out cross-validation. RESULTS: Within 1 year after SBRT, 15 of 95 vertebral levels included in the analysis demonstrated new or progressive VCF. Selected clinical features included BMI, performance status, total prescription dose, dose to 99% of the PTV, lumbar location, and 2 components of the Spine Instability Neoplastic Score (SINS): lytic tumor character and spinal misalignment. Selected radiomic features included 5 features from CT and 3 features from MRI. The best-performing classification model, derived from a combination of selected clinical and radiomic features, demonstrated a sensitivity of 0.844, specificity of 0.800, and area under the receiver operating characteristic (ROC) curve (AUC) of 0.878. This model was significantly more accurate than alternative models derived from only selected clinical features (AUC = 0.795, p = 0.048) or only components of the SINS (AUC = 0.579, p < 0.0001). CONCLUSIONS: In the treatment of spinal metastases with SBRT, a machine learning model incorporating both clinical features and radiomic features from pretreatment imaging predicted VCF at 1 year after SBRT with excellent sensitivity and specificity, outperforming models developed from clinical features or components of the SINS alone. If validated, these findings may allow more judicious selection of patients for prophylactic interventions.