Advancements and future directions in positron emission tomography-guided radiotherapy: a narrative review.

BACKGROUND AND OBJECTIVE: Positron emission tomography (PET) imaging has been useful in delineating tumor volumes and allowing for improved radiation treatment. The field of PET-guided radiotherapy is rapidly growing and will have significant impact on radiotherapy delivery in the future. This narrative review provides an overview of the current state of PET-guided radiotherapy as well as the future directions of the field. METHODS: For this narrative review, PubMed was searched for articles from 2010-2023. A total of 18 keywords or phrases were searched to provide an overview of PET-guided radiotherapy, radiotracers, the role of PET-guided radiotherapy in oligometastatic disease, and biology-guided radiotherapy (BgRT). The first 300 results for each keyword were searched and relevant articles were extracted. The references of these articles were also reviewed for relevant articles. KEY CONTENT AND FINDINGS: In radiotherapy, 18F-2-fluoro-2-deoxy-D-glucose (F-FDG or FDG) is the major radiotracer for PET and when combined with computed tomography (CT) scan allows for anatomic visualization of metabolically active malignancy. Novel radiotracers are being explored to delineate certain cell types and numerous tumor metrics including metabolism, hypoxia, vascularity, and cellular proliferation. This molecular and functional imaging will provide improved tumor characterization. Through these radiotracers, radiation plans can employ dose painting by creating different dose levels based upon specific risk factors of the target volume. Additionally, biologic imaging during radiotherapy can allow for adaptation of the radiation plan based on response to treatment. Dose painting and adaptive radiotherapy should improve the therapeutic ratio through more selective dose delivery. The novel PET-linear accelerator hopes to combine these techniques and more by using radiotracers to deliver BgRT. The areas of radiotracer uptake will serve as fiducials to guide radiotherapy to themselves. This technique may prove promising in the growing area of oligometastatic radiation treatment. CONCLUSIONS: Significant challenges exist for the future of PET-guided radiotherapy. However, with the advancements being made, PET imaging is set to change the delivery of radiotherapy.

A repository of grade 1 and 2 meningioma MRIs in a public dataset for radiomics reproducibility tests.

PURPOSE: Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA). ACQUISITION AND VALIDATION METHODS: The dataset consists of pre-operative MRIs from 96 patients with meningiomas who underwent resection from 2010-2019 and include axial T1post and T2-FLAIR sequences-55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2-FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1 × 1 × 1 mm3 . The entire dataset was reviewed by a certified medical physicist. DATA FORMAT AND USAGE NOTES: The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV-1A36. The total size of the dataset is 8.8GB, with 47 519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures. POTENTIAL APPLICATIONS: Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision-making. This dataset will allow researchers to create models to auto-differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults.

StrataXRT for the prevention and treatment of radiation dermatitis: a critical review.

PURPOSE: The primary objective is to systematically review primary studies, such as randomized control trials (RCTs), feasibility, exploratory, and case studies; and the secondary objective is to evaluate all secondary articles, such as reviews, guidelines, and editorials, relevant to the use of StrataXRT for the prevention and/or management of radiation dermatitis (RD) in cancer patients. METHODS: A literature search was conducted up to February 26, 2023, for articles investigating the use of StrataXRT for the prevention and treatment of RD, in the following databases: Ovid MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar. The keywords "StrataXRT", "dermatitis", "radiotherapy", and "radiation" were used to identify relevant articles. RESULTS: Twenty-seven articles from 2018 to 2022 were identified to fulfill the inclusion criteria of this review, of which nine are primary studies and 18 are secondary papers. Significant heterogeneity was observed in the current literature studying the effects of StrataXRT, making it difficult to make cross-trial comparisons. There is a suggestion of the efficacy of StrataXRT in the prevention and treatment of RD. CONCLUSION: The findings of this review recommend further adequately powered RCTs with robust methodology including patient and clinician assessments to determine the efficacy of StrataXRT in preventing and treating RD. This is essential to improve the quality of life of patients and identify which groups of patients would benefit most from StrataXRT.

Comparison of preoperative versus postoperative treatment dosimetry plans of single-fraction stereotactic radiosurgery for surgically resected brain metastases.

OBJECTIVE: Stereotactic radiosurgery (SRS) for operative brain metastasis (BrM) is usually administered 1 to 6 weeks after resection. Preoperative versus postoperative timing of SRS delivery related to surgery remains a critical question, as a pattern of failure is the development of leptomeningeal disease (LMD) in as many as 35% of patients who undergo postoperative SRS or the occurrence of radiation necrosis. As they await level I clinical data from ongoing trials, the authors aimed to bridge the gap by comparing postoperative with simulated preoperative single-fraction SRS dosimetry plans for patients with surgically resected BrM. METHODS: The authors queried their institutional database to retrospectively identify patients who underwent postoperative Gamma Knife SRS (GKSRS) after resection of BrM between January 2014 and January 2021. Exclusion criteria were prior radiation delivered to the lesion, age < 18 years, and prior diagnosis of LMD. Once identified, a simulated preoperative SRS plan was designed to treat the unresected BrM and compared with the standard postoperative treatment delivered to the resection cavity per Radiation Therapy Oncology Group (RTOG) 90-05 guidelines. Numerous comparisons between preoperative and postoperative GKSRS treatment parameters were then made using paired statistical analyses. RESULTS: The authors' cohort included 45 patients with a median age of 59 years who were treated with GKSRS after resection of a BrM. Primary cancer origins included colorectal cancer (27%), non-small cell lung cancer (22%), breast cancer (11%), melanoma (11%), and others (29%). The mean tumor and cavity volumes were 15.06 cm3 and 12.61 cm3, respectively. In a paired comparison, there was no significant difference in the planned treatment volumes between the two groups. When the authors compared the volume of surrounding brain that received 12 Gy or more (V12Gy), an important predictor of radiation necrosis, 64% of patient plans in the postoperative SRS group (29/45, p = 0.008) recorded greater V12 volumes. Preoperative plans were more conformal (p < 0.001) and exhibited sharper dose drop-off at the lesion margins (p = 0.0018) when compared with postoperative plans. CONCLUSIONS: Comparison of simulated preoperative and delivered postoperative SRS plans administered to the BrM or resection cavity suggested that preoperative SRS allows for more highly conformal lesional coverage and sharper dose drop-off compared with postoperative plans. Furthermore, V12Gy was lower in the presurgical GKSRS plans, which may account for the decreased incidence of radiation necrosis seen in prior retrospective studies.

StrataXRT for the prevention of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: To evaluate the overall efficacy of StrataXRT, a topical gel dressing, in preventing acute radiation dermatitis (RD) in breast cancer patients undergoing radiotherapy (RT). METHODS: A systematic search was conducted on April 25, 2023 in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Randomized controlled trials (RCTs) assessing the effectiveness of StrataXRT in preventing acute RD in breast cancer patients undergoing adjuvant RT to the breast or chest wall with or without regional nodes were included. Pooled incidence odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model, with analysis and forest plots generated in RevMan v5.4. RESULTS: The analysis included three RCTs with a total of 189 patients assessed using per-protocol analysis. Two RCTs compared StrataXRT to standard of care, while the third compared it with Mepitel film and was reported separately. In the former RCTs, the odds ratio (OR) for developing acute grade 3 RD favored StrataXRT at 0.05 (95% CI, 0.01-0.22; P < 0.0001). The OR for developing acute grades 2-3 RD was 0.32 (95% CI, 0.03-3.18; P = 0.33). The RCT comparing StrataXRT with Mepitel film showed insignificant ORs for grade 3 and grades 2-3 RD. One RCT reported significantly lower erythema index (P = 0.008) and melanin index (P = 0.015) in StrataXRT patients. The use of StrataXRT did not raise additional safety concerns. CONCLUSION: StrataXRT may help prevent severe acute RD in breast cancer RT patients. Further high quality, large-scale studies are needed to confirm these findings.

Mepitel film for the prevention and treatment of acute radiation dermatitis in breast cancer: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: This systematic review and meta-analysis aimed to evaluate the efficacy of Mepitel film in preventing or treating acute radiation dermatitis (RD) in patients with breast cancer in randomized controlled trials (RCTs). METHODS: Embase, APA PsychInfo, Journals@Ovid Full Text, Ovid MEDLINE, PubMed, and Cochrane Trials were searched until December 12, 2022, to identify RCTs on the use of Mepitel film for preventing or treating acute RD from breast cancer radiotherapy. Per-protocol analysis was used to compare outcomes, calculate pooled effect sizes, odds ratio (OR), and 95% confidence intervals (CI), and to create forest plots using random effects analysis in RevMan 5.4. RESULTS: Three RCTs were included in this review. Mepitel film significantly reduced the incidence of grade 3 RD (OR 0.15 95% CI 0.06, 0.37, p<0.0001) and grade 2 or 3 RD (OR 0.16 95% CI 0.04, 0.65, p=0.01) as scored on either the CTCAE or the RTOG scale. Additionally, Mepitel film significantly reduced RISRAS mean scores assessed by patients and combined researcher and patient (standardized mean difference (SMD) -7.59, 95% CI -14.42, -0.76, p=0.03; SMD -15.36, 95% CI -30.01, -0.71 p=0.04) but not the researcher component of the assessment tool (SMD -17.55, 95% CI -36.94, 1.84, p=0.08). CONCLUSION: Mepitel film reduced the incidence of acute RD and improved patient-reported outcomes with minimal side effects, the main one being itchiness. Future research should assess the feasibility of Mepitel film with respect to specific patient-reported outcomes such as health-related quality of life issues associated with its use.

Adjuvant chemotherapy, not radiotherapy, prolongs survival for node-negative non-small cell lung cancer with positive surgical margins.

Objective: The study objective was to determine differences in survival depending on adjuvant therapy type, timing, and sequence in node-negative disease with positive margins after non-small cell lung cancer resection. Methods: The National Cancer Database was queried for patients with positive margins after surgical resection of treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer who underwent adjuvant radiotherapy or chemotherapy from 2010 to 2016. Adjuvant treatment groups were defined as surgery alone, chemotherapy alone, radiotherapy alone, concurrent chemoradiotherapy, sequential chemotherapy then radiotherapy, and sequential radiotherapy then chemotherapy. The impact of adjuvant radiotherapy initiation timing on survival was evaluated using multivariable Cox regression. Kaplan-Meier curves were generated to compare 5-year survival. Results: A total of 1713 patients met inclusion criteria. Five-year survival estimates differed significantly between cohorts: surgery alone, 40.7%; chemotherapy alone, 47.0%; radiotherapy alone, 35.1%; concurrent chemoradiotherapy, 45.7%; sequential chemotherapy then radiotherapy, 36.6%; and sequential radiotherapy then chemotherapy, 32.2% (P = .033). Compared with surgery alone, adjuvant radiotherapy alone had a lower estimated survival at 5 years, although overall survival did not differ significantly (P = .8). Chemotherapy alone improved 5-year survival compared with surgery alone (P = .0016) and provided a statistically significant survival advantage over adjuvant radiotherapy (P = .002). Compared with radiotherapy-inclusive multimodal therapies, chemotherapy alone yielded similar 5-year survival (P = .066). Multivariable Cox regression showed an inverse linear association between time to adjuvant radiotherapy initiation and survival, but with an insignificant trend (10-day hazard ratio, 1.004; P = .90). Conclusions: In treatment-naïve cT1-4N0M0 pN0 non-small cell lung cancer with positive surgical margins, only adjuvant chemotherapy was associated with a survival improvement compared with surgery alone, with no radiotherapy-inclusive treatment providing additional survival benefit. Delayed timing of radiotherapy initiation was not associated with a survival reduction.

Pilot Study Demonstrating the Value of Interdisciplinary Education on the Integration of Radiation Therapy in Lung Cancer Management.

This study aimed to understand baseline knowledge of basic principles of radiation therapy for lung cancer among medical oncology, thoracic surgery, and pulmonology trainees and practicing physicians and also assess whether a didactic lecture will improve objective knowledge and perceived comfort level in making appropriate referrals to radiation oncology (RO). Radiation oncologists at 8 academic institutions offered a presentation covering indications, logistics, efficacy, and toxicity of thoracic radiation. Participants completed a survey to assess their prior exposures to RO and perceived value of the lecture, and objective knowledge gained based on pre/post-lecture questions. Among 121 attendees, 76 completed the pre-test, and 25 the post-test (response rates 62.8% and 20.7%, respectively). Fifty-seven (75.0%) had never previously experienced a RO didactic about lung cancer, 62 (81.6%) had never seen a linear accelerator, and 65 (85.5%) had never rotated in a RO department. The mean pre-test score was 53.5% (SD 17.6%), with a trend (p = 0.066) towards thoracic surgeons (61.5%) performing better than medical oncologists (55.5%) or pulmonologists (48.3%). Level of training (p = 0.130), and prior RO exposures (p = 0.240), did not significantly impact pre-test scores. The mean post-test score of 75.1% (SD 3.6%) was significantly higher than mean pre-test score (p < 0.001). After the lecture, 25 participants (100%) felt more knowledgeable about RO, and 24 (96%) felt more comfortable making appropriate referrals to RO. A didactic lecture about RO for trainees and physicians who treat lung cancer at 8 academic institutions was feasible, filled a gap in exposure, and improved knowledge.

Integration of Universal Germline Genetic Testing for All New Breast Cancer Patients.

BACKGROUND: The American Society of Breast Surgeons recommends genetic testing (GT) for all women with breast cancer (BC), but implementation and uptake of GT has not been well-described. METHODS: A retrospective chart review was performed for newly diagnosed BC patients or patients with a newly identified recurrence of BC seen in a multidisciplinary clinic (MDBC) who were offered genetic counseling (GC) and GT. RESULTS: The 138 women attending the MDBC had a median age of 54 years and comprised non-Hispanic whites (46%), Asians (28%), Hispanics (17%), blacks (4%), and other (5%). Of the 105 (76%) patients without prior GT, 100 (95%) accepted GC, with 93 (93%) of these 100 patients undergoing GT. The patients meeting the National Comprehensive Cancer Network (NCCN) guidelines for GT were more likely to undergo GT. Testing was performed with a 67- to 84-gene panel, together with an 8- to 9-gene STAT panel if needed. Among 120 patients with reports available, including 33 patients previously tested, 15 (12%) were positive (1 BLM, 1 BRCA1, 3 BRCA2, 1 BRIP1, 1 CFTR, 1 CHEK2, 1 MUTYH, 1 PALB2, 1 PRSS1, 1 RAD50, 1 RET, and 2 TP53), 44 (37%) were negative, and 61 (51%) had an uncertain variant. The median time to STAT results (n = 50) was 8 days. The STAT results were available before surgery for 47 (98%) of the 48 STAT patients undergoing surgery. CONCLUSIONS: New BC patients attending the MDBC demonstrated high rates of acceptance of GC and GT. The combination of GC and GT can offer timely information critical to patient risk assessment and treatment planning.

Patterns of Use of Stereotactic Body Radiation Therapy Compared With Surgery for Definitive Treatment of Primary Early-stage Non-small Cell Lung Cancer.

OBJECTIVE: As stereotactic body radiation therapy (SBRT) becomes widely available for early-stage non-small cell lung cancer (NSCLC), there may be concerns in the surgical community that SBRT is being offered for patients with operable tumors, even though surgery is standard of care. We evaluated the trends in SBRT and surgery over time for patients with NSCLC. MATERIALS AND METHODS: The National Cancer Database was queried for patients with node-negative NSCLC ≤5 cm from 2004 to 2016. The relationships between definitive local treatment modalities and year were analyzed using a multinomial regression model while controlling for other covariates. RESULTS: Among the 202,367 patients who met the inclusion criteria, there was a steady decrease in mean tumor size in all treatment modalities, from 2.44 cm (SD=1.08) to 2.25 cm (SD=1.00) over the study period. In the multinomial model, the probability of receiving lobectomy demonstrated a slight decline from 58% (2004) to 53% (2016). The use of SBRT increased from 1% to 20%, while patients receiving no therapy declined from 27% to 16%. The likelihood of SBRT increased with year of diagnosis (P<0.0001) and decreasing tumor size (P<0.0001), compared with lobectomy. Age, race, income, facility, and Charlson-Deyo score were also associated with treatment modality. CONCLUSIONS: The mean tumor size of early-stage NSCLC decreased over the study period for all treatment modalities. SBRT use has increased, mostly among older patients with smaller tumors and Charlson-Deyo scores ≥3. The increase in SBRT contributed to the significant decline in patients who had no therapy.

Automatic differentiation of Grade I and II meningiomas on magnetic resonance image using an asymmetric convolutional neural network.

The Grade of meningioma has significant implications for selecting treatment regimens ranging from observation to surgical resection with adjuvant radiation. For most patients, meningiomas are diagnosed radiologically, and Grade is not determined unless a surgical procedure is performed. The goal of this study is to train a novel auto-classification network to determine Grade I and II meningiomas using T1-contrast enhancing (T1-CE) and T2-Fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) images. Ninety-six consecutive treatment naïve patients with pre-operative T1-CE and T2-FLAIR MR images and subsequent pathologically diagnosed intracranial meningiomas were evaluated. Delineation of meningiomas was completed on both MR images. A novel asymmetric 3D convolutional neural network (CNN) architecture was constructed with two encoding paths based on T1-CE and T2-FLAIR. Each path used the same 3 × 3 × 3 kernel with different filters to weigh the spatial features of each sequence separately. Final model performance was assessed by tenfold cross-validation. Of the 96 patients, 55 (57%) were pathologically classified as Grade I and 41 (43%) as Grade II meningiomas. Optimization of our model led to a filter weighting of 18:2 between the T1-CE and T2-FLAIR MR image paths. 86 (90%) patients were classified correctly, and 10 (10%) were misclassified based on their pre-operative MRs with a model sensitivity of 0.85 and specificity of 0.93. Among the misclassified, 4 were Grade I, and 6 were Grade II. The model is robust to tumor locations and sizes. A novel asymmetric CNN with two differently weighted encoding paths was developed for successful automated meningioma grade classification. Our model outperforms CNN using a single path for single or multimodal MR-based classification.

Temporality and Patterns of Metastatic Recurrence in Node-Positive Breast Cancer Following Trimodality Therapy: Opportunity for Improved Oligometastases Detection and Salvage Local Therapy.

OBJECTIVES: There is evidence that detection and treatment of oligometastases (≤5 lesions) may improve survival in breast cancer patients. However, there are no current national guidelines for screening of early, asymptomatic metastases. This study examined the patterns and timing of recurrence with respect to survival in node-positive breast cancer (NPBC) patients at higher risk for developing metastases. METHODS: A single-institution retrospective review of NPBC patients treated with trimodality therapy was performed to collect patient and disease characteristics, recurrence location, method of detection, and survival outcome. Univariate and multivariate analyses were done to identify factors associated with recurrence. RESULTS: Ninety-four NPBC patients treated at a safety-net hospital between 2008 and 2019 were identified. Twenty-one developed recurrence and were divided into oligometastatic (OM) (n=10) or diffusely metastatic (DM) (n=11) subgroups. Median recurrence-free survival in OM and DM was 18 and 36 months, respectively. Median overall survival (OS) for OM was not reached. Median OS for DM was 57 months. Four patients with OM progressed to diffuse disease in a median period of 17 months; median survival thereafter was 57 months. All patients with recurrence had distant metastases on initial detection, with the most common site being bone (14). Recurrence was most frequently detected by computed tomography (CT) (13), with the majority of disease located within the thorax region. CONCLUSIONS: All NPBC patients had distant metastasis at time of recurrence. Patients with OM had shorter interval to recurrence yet longer OS compared with DM. This study highlights improved surveillance imaging for timely detection of OM breast cancer that may yet be amenable to aggressive local salvage therapy to prevent progression to diffuse disease.

Voxelwise Prediction of Recurrent High-Grade Glioma via Proximity Estimation-Coupled Multidimensional Support Vector Machine.

PURPOSE: To provide early and localized glioblastoma (GBM) recurrence prediction, we introduce a novel postsurgery multiparametric magnetic resonance-based support vector machine (SVM) method coupling with stem cell niche (SCN) proximity estimation. METHODS AND MATERIALS: This study used postsurgery magnetic resonance imaging (MRI) scans from 50 patients with recurrent GBM, obtained approximately 2 months before clinically diagnosed recurrence. The main prediction pipeline consisted of a proximity-based estimator to identify regions with high risk of recurrence (HRRs) and an SVM classifier to provide voxelwise prediction in HRRs. The HRRs were estimated using the weighted sum of inverse distances to 2 possible origins of recurrence-the SCN and the tumor cavity. Subsequently, multiparametric voxels (from T1, T1 contrast-enhanced, fluid-attenuated inversion recovery, T2, and apparent diffusion coefficient) within the HRR were grouped into recurrent (warped from the clinical diagnosis) and nonrecurrent subregions and fed into the proximity estimation-coupled SVM classifier (SVMPE). The cohort was randomly divided into 40% and 60% for training and testing, respectively. The trained SVMPE was then extrapolated to an earlier time point for earlier recurrence prediction. As an exploratory analysis, the SVMPE predictive cluster sizes and the image intensities from the 5 magnetic resonance sequences were compared across time to assess the progressive subclinical traces. RESULTS: On 2-month prerecurrence MRI scans from 30 test cohort patients, the SVMPE classifier achieved a recall of 0.80, a precision of 0.69, an F1-score of 0.73, and a mean boundary distance of 7.49 mm. Exploratory analysis at early time points showed spatially consistent but significantly smaller subclinical clusters and significantly increased T1 contrast-enhanced and apparent diffusion coefficient values over time. CONCLUSIONS: We demonstrated a novel voxelwise early prediction method, SVMPE, for GBM recurrence based on clinical follow-up MR scans. The SVMPE is promising in localizing subclinical traces of recurrence 2 months ahead of clinical diagnosis and may be used to guide more effective personalized early salvage therapy.

Surviving Over a Decade With Glioblastoma: A Clinical Course Characterized by Multiple Recurrences, Numerous Salvage Treatments, and Novel Use of Cesium-131 Tiles.

The prognosis for patients diagnosed with recurrent glioblastoma (GBM) remains poor, with no clear standard of care regarding salvage therapy. Common approaches include chemotherapy, re-resection, tumor treating fields, and reirradiation. However, most studies have shown these to have limited benefits. Reirradiation is particularly difficult due to concern for increased risk of toxicity to surrounding normal brain tissue. A novel intracranial brachytherapy system called GammaTile® (GT Medical Technologies, Tempe, Arizona) involves the placement of Cesium-131 radioactive tiles in the tumor cavity following maximal safe resection. This allows for a highly conformal dose distribution with rapid fall-off to minimize overlap with prior radiation fields and for the application of radiation directly to the high-risk tumor bed. This case report highlights a patient with GBM who survived 11.5 years through multiple recurrences and discusses the many salvage treatments he received, including bevacizumab, irinotecan, and stereotactic radiosurgery (SRS). This case exemplifies that aggressive systemic and local therapies can work well in select patients allowing for long-term survival with a good quality of life. Further efforts should be made to identify which patients may benefit from these therapies. The case study additionally reports on the use of GammaTile therapy. Due to prior external beam radiation therapy and SRS to the treatment site, further external beam radiation options were limited, and the patient was offered GammaTile as local therapy. Although it did not provide a survival benefit in this case due to progressive disease outside of the field of treatment, GammaTile serves as a valuable option in providing local therapy to patients who can no longer receive further radiation. It should be used with careful consideration in lesions characterized by aggressive local invasion.

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.

Automatic detection and segmentation of multiple brain metastases on magnetic resonance image using asymmetric UNet architecture.

Detection of brain metastases is a paramount task in cancer management due both to the number of high-risk patients and the difficulty of achieving consistent detection. In this study, we aim to improve the accuracy of automated brain metastasis (BM) detection methods using a novel asymmetric UNet (asym-UNet) architecture. An end-to-end asymmetric 3D-UNet architecture, with two down-sampling arms and one up-sampling arm, was constructed to capture the imaging features. The two down-sampling arms were trained using two different kernels (3 × 3 × 3 and 1 × 1 × 3, respectively) with the kernel (1 × 1 × 3) dominating the learning. As a comparison, vanilla single 3D UNets were trained with different kernels and evaluated using the same datasets. Voxel-based Dice similarity coefficient (DSCv), sensitivity (S v), precision (P v), BM-based sensitivity (S BM), and false detection rate (F BM) were used to evaluate model performance. Contrast-enhanced T1 MR images from 195 patients with a total of 1034 BMs were solicited from our institutional stereotactic radiosurgery database. The patient cohort was split into training (160 patients, 809 lesions), validation (20 patients, 136 lesions), and testing (15 patients, 89 lesions) datasets. The lesions in the testing dataset were further divided into two subgroups based on the diameters (small S = 1-10 mm, large L = 11-26 mm). In the testing dataset, there were 72 and 17 BMs in the S and L sub-groups, respectively. Among all trained networks, asym-UNet achieved the highest DSCv of 0.84 and lowest F BM of 0.24. Although vanilla 3D-UNet with a single 1 × 1 × 3 kernel achieved the highest sensitivities for the S group, it resulted in the lowest precision and highest false detection rate. Asym-UNet was shown to balance sensitivity and false detection rate as well as keep the segmentation accuracy high. The novel asym-UNet segmentation network showed overall competitive segmentation performance and more pronounced improvement in hard-to-detect small BMs comparing to the vanilla single 3D UNet.

Trimodality vs Chemoradiation and Salvage Resection in cN2 Stage IIIA Non-Small Cell Lung Cancer.

To determine the overall survival (OS) in patients who underwent planned trimodality therapy (TMT) and those who underwent definitive concurrent chemoradiation (CRT), but later received salvage resection (SR) for stage IIIA (cN2) (AJCC 7th ed.) non-small cell lung cancer. National Cancer Database data set from 2004 to 2014 was queried. TMT was defined as multiagent CRT with dose >45 Gy, followed by lobectomy or pneumonectomy ≤90 days from end of CRT. SR was defined as multiagent CRT with dose >59 Gy and lobectomy or pneumonectomy performed >90 days from CRT completion. Propensity score weighting and propensity score matching methods were used to balance patient and tumor characteristics and to calculate hazard ratios. A total of 2025 (1899 TMT and 126 SR) patients were analyzed. TMT and SR groups shared similar characteristics. Surgery occurred at a median of 41 days (range 1-90) after CRT in the TMT group and 114 days (91-440) in the SR group. The 90-day mortality after surgery was 6.5% for TMT and 5% for SR (P = 0.43). The 3- and 5-year OS were 55.1% and 35.7% for TMT and 51.6% and 45.0% for SR (P = 0.92, 0.68), with no difference across unadjusted cohort and propensity-adjusted cohort. Patients with cN2 stage IIIA non-small cell lung cancer treated in the United States with definitive CRT followed by SR had similar OS as upfront TMT with similar postoperative mortality despite SR occurring >90 days after >59 Gy CRT. SR remains an option for medically appropriate patients after definitive dose CRT.

Stereotactic radiosurgery and ipilimumab for patients with melanoma brain metastases: clinical outcomes and toxicity.

INTRODUCTION: There is evidence that the combination of ipilimumab and stereotactic radiosurgery (SRS) for brain metastases improves outcomes. We investigated clinical outcomes, radiation toxicity, and impact of ipilimumab timing in patients treated with SRS for melanoma brain metastases. METHODS: We retrospectively identified 91 patients treated with SRS at our institution for melanoma brain metastases from 2006 to 2015. Concurrent ipilimumab administration was defined as within ± 4 weeks of SRS procedure. Acute and late toxicities were graded with CTCAE v4.03. Overall survival (OS), local failure, distant brain failure, and failure-free survival were analyzed with the Kaplan-Meier method. OS was analyzed with Cox regression. RESULTS: Twenty-three patients received ipilimumab concurrent with SRS, 28 patients non-concurrently, and 40 patients did not receive ipilimumab. The median age was 62 years and 91% had KPS ≥ 80. The median follow-up time was 7.4 months. Patients who received ipilimumab had a median OS of 15.1 months compared to 7.8 months in patients who did not (p = 0.02). In multivariate analysis, ipilimumab (p = 0.02) and diagnosis-specific graded prognostic assessment (p = 0.02) were associated with OS. There were no differences in intracranial control by ipilimumab administration or timing. The incidence of radiation necrosis was 5%, with most events occurring in patients who received ipilimumab. CONCLUSIONS: Patients who received ipilimumab had improved OS even after adjusting for prognostic factors. Ipilimumab did not appear to increase risk for acute toxicity. The majority of radiation necrosis events, however, occurred in patients who received ipilimumab. Our results support the continued use of SRS and ipilimumab as clinically appropriate.