Clinical Outcome in Patients With Early-Stage Small Cell Lung Cancer Treated With Surgery or Radiation in the Absence of Prophylactic Cranial Irradiation: A Single-Center Retrospective Study.

Purpose: As screening chest computed tomography for patients at high risk for cancer has become more widely accepted, increasing numbers of patients with early-stage small cell lung cancer (SCLC) are being diagnosed. Although surgery is an accepted option for patients with early-stage SCLC, for patients who decline or cannot undergo surgery, stereotactic body radiation treatment (SBRT) is an alternative. Although prophylactic cranial irradiation (PCI) improves survival in patients with limited-stage SCLC, PCI for early-stage SCLC (stage T1-T2) has not been explored. This study defines survival and recurrence patterns in patients with early-stage SCLC who were treated with surgery or SBRT in the absence of PCI. Methods and Materials: In this single-institution retrospective study, 14 patients diagnosed with early-stage SCLC (stage T1-T2) between July 2015 and May 2021 at a single tertiary care hospital were treated with SBRT or surgery with no PCI. Primary outcomes were locoregional cancer recurrence, distant recurrence, recurrence-free survival, and overall survival. The secondary outcome was development of brain metastasis. Analyses included Cox regression, Kaplan-Meier survival, and log-rank tests. Results: A total of 14 patients (5 women and 9 men) were included in the study: 9 with stage T1 and 5 with stage T2 SCLC. Six patients (43%) received SBRT and 8 (57%) had surgical treatment. All patients except 1 received adjuvant chemotherapy. Median follow-up was 14.3 months (range, 2.4-64.4 months), and the median age at diagnosis was 71.5 years (range, 54-81 years). Cox regression and log-rank tests showed no significant differences in any outcomes between the surgery and SBRT groups, and no patients developed brain metastases during the study period. Conclusions: Data are lacking regarding the benefit of PCI in early-stage SCLC. Although the sample size in this study was too small to draw any conclusions, the findings add to the ongoing dialogue regarding the importance of PCI in this patient population. No difference was identified in survival and cancer recurrence in patients who received either surgery or SBRT in the absence of PCI.

Feasibility of radical cardiac-sparing, treatment planning strategies for patients with locally advanced, non-small cell lung cancer.

PURPOSE: A set of treatment planning strategies were designed and retrospectively implemented for locally advanced, non-small cell lung cancer (NSCLC) patients in order to minimize cardiac dose without compromising target coverage goals. METHODS: Retrospective analysis was performed for 20 NSCLC patients prescribed to 60-66 Gy that received a mean heart dose (MHD) ≥10 Gy. Three planning approaches were designed and implemented. The first was a multi-isocentric (MI) volume-modulated arc therapy (VMAT) approach (HEART_MI) with one isocenter located within the tumor and the second chosen up to 10 cm away longitudinally. The second was a noncoplanar (NCP) VMAT approach (HEART_NCP) utilizing up to three large couch angles and a standard arc at couch 0. The final planning strategy took a mixed approach (HEART_HYBRID) utilizing the HEART_NCP strategy for two thirds of the treatment combined with a plan utilizing a pair of opposite-opposed gantry angles for the remaining treatments. Investigational plans were compared to original plans using dose-volume histogram metrics such as organ volume receiving greater than x Gy (Vx) or mean dose (Dmean). RESULTS: Although there was a small but statistically significant decrease in internal target volume coverage for HEART_MI plans and, conversely, a statistically significant increase for HEART_NCP plans, all generated plans met physician-prescribed target constraints. For heart dose, there were statistically significant decreases in all heart metrics and particularly MHD for the HEART_MI (9.8 vs. 15.4 Gy [p < 0.001], respectively), HEART_NCP (9.2 vs. 15.4 Gy [p < 0.001]), respectively), and HEART_HYBRID (7.9 vs. 15.4 Gy [p < 0.001], respectively) strategies. CONCLUSIONS: The strategy providing the best compromise between plan quality and cardiac dose reduction was HEART_NCP, which produced MHD reductions of 37.6% ± 12.9% (6.2 ± 3.4 Gy) relative to original plans. This strategy could potentially reduce adverse cardiac events, leading to improved quality of life for these patients.

MRI-guided Radiotherapy (MRgRT) for Treatment of Oligometastases: Review of Clinical Applications and Challenges.

PURPOSE: Early clinical results on the application of magnetic resonance imaging (MRI) coupled with a linear accelerator to deliver Magnetic Resonance-guided Radiation Therapy (MRgRT) have demonstrated feasibility for safe delivery of stereotactic body radiation therapy in treatment of oligometastatic disease. Here, we set out to review the clinical evidence and challenges associated with MRgRT in this setting. METHODS AND MATERIALS: We performed a systematic review of the literature pertaining to clinical experiences and trials on the use of MRgRT primarily for the treatment of oligometastatic cancers. We reviewed the opportunities and challenges associated with the use of MRgRT. RESULTS: Benefits of MRgRT pertaining to superior soft-tissue contrast, real-time imaging and gating, and online adaptive radiation therapy facilitate safe and effective dose escalation to oligometastatic tumors while simultaneously sparing surrounding healthy tissues. Challenges concerning further need for clinical evidence and technical considerations related to planning, delivery, quality assurance of hypofractionated doses, and safety in the MRI environment must be considered. CONCLUSIONS: The promising early indications of safety and effectiveness of MRgRT for stereotactic body radiation therapy-based treatment of oligometastatic disease in multiple treatment locations should lead to further clinical evidence to demonstrate the benefit of this technology.

An Analysis of Clinical Toxic Effects and Quality of Life as a Function of Radiation Dose and Volume After Lung Stereotactic Body Radiation Therapy.

PURPOSE: To analyze clinical toxicity and quality-of-life (QOL) outcomes among patients with stage I non-small cell lung cancer (NSCLC) after stereotactic body radiation therapy (SBRT) as a function of radiation dose and volume parameters. METHODS AND MATERIALS: In this institutional review board-approved study, 55 patients with stage I NSCLC who received SBRT (12 Gy × 4) and completed QOL forms were analyzed. Clinical symptoms and QOL outcomes were measured at baseline and at 3, 6, 12, 18, 24, and 36 months after SBRT. Clinical toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0. Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Lung-Trial Outcome Index (FACT-L-TOI) instrument. Dosimetric parameters including the mean lung radiation dose and the volume of normal lung receiving greater than 5, 10, 13, or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student t tests and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxic effects. The Kaplan-Meier method was used to estimate rates of local control (LC), disease-free survival (DFS), and overall survival (OS). RESULTS: With a median follow-up of 24 months, the 3-year LC, DFS, and OS were 93%, 65%, and 84%, respectively, with a 5.5% rate of grade-3 toxic effects and no grade 4 or 5 toxic effects. Clinically meaningful declines in patient-reported QOL (FACT-L-TOI, lung cancer subscale, physical well-being, and/or functional well-being) posttreatment significantly correlated with increased dosimetric parameters such as V10, V13, and V20. CONCLUSION: Although lung SBRT was associated with excellent LC and minimal clinical toxic effects for early-stage NSCLC, clinically meaningful declines in QOL were significantly correlated with increasing lung dose and volume parameters.

A Grade I Intracranial Meningioma with Metastasis to Multiple Vertebral Bodies: A Case Report and Literature Review.

World Health Organization (WHO) grade I meningiomas are slow-growing and typically benign brain tumors that can often be easily removed by surgery and rarely become malignant. We report the case of a WHO grade I meningioma in a 67-year-old man with multiple extracranial metastases.

Segmentation of the Prostatic Gland and the Intraprostatic Lesions on Multiparametic Magnetic Resonance Imaging Using Mask Region-Based Convolutional Neural Networks.

PURPOSE: Accurate delineation of the prostate gland and intraprostatic lesions (ILs) is essential for prostate cancer dose-escalated radiation therapy. The aim of this study was to develop a sophisticated deep neural network approach to magnetic resonance image analysis that will help IL detection and delineation for clinicians. METHODS AND MATERIALS: We trained and evaluated mask region-based convolutional neural networks to perform the prostate gland and IL segmentation. There were 2 cohorts in this study: 78 public patients (cohort 1) and 42 private patients from our institution (cohort 2). Prostate gland segmentation was performed using T2-weighted images (T2WIs), although IL segmentation was performed using T2WIs and coregistered apparent diffusion coefficient maps with prostate patches cropped out. The IL segmentation model was extended to select 5 highly suspicious volumetric lesions within the entire prostate. RESULTS: The mask region-based convolutional neural networks model was able to segment the prostate with dice similarity coefficient (DSC) of 0.88 ± 0.04, 0.86 ± 0.04, and 0.82 ± 0.05; sensitivity (Sens.) of 0.93, 0.95, and 0.95; and specificity (Spec.) of 0.98, 0.85, and 0.90. However, ILs were segmented with DSC of 0.62 ± 0.17, 0.59 ± 0.14, and 0.38 ± 0.19; Sens. of 0.55 ± 0.30, 0.63 ± 0.28, and 0.22 ± 0.24; and Spec. of 0.974 ± 0.010, 0.964 ± 0.015, and 0.972 ± 0.015 in public validation/public testing/private testing patients when trained with patients from cohort 1 only. When trained with patients from both cohorts, the values were as follows: DSC of 0.64 ± 0.11, 0.56 ± 0.15, and 0.46 ± 0.15; Sens. of 0.57 ± 0.23, 0.50 ± 0.28, and 0.33 ± 0.17; and Spec. of 0.980 ± 0.009, 0.969 ± 0.016, and 0.977 ± 0.013. CONCLUSIONS: Our research framework is able to perform as an end-to-end system that automatically segmented the prostate gland and identified and delineated highly suspicious ILs within the entire prostate. Therefore, this system demonstrated the potential for assisting the clinicians in tumor delineation.

A deep dive into understanding tumor foci classification using multiparametric MRI based on convolutional neural network.

PURPOSE: Deep learning models have had a great success in disease classifications using large data pools of skin cancer images or lung X-rays. However, data scarcity has been the roadblock of applying deep learning models directly on prostate multiparametric MRI (mpMRI). Although model interpretation has been heavily studied for natural images for the past few years, there has been a lack of interpretation of deep learning models trained on medical images. In this paper, an efficient convolutional neural network (CNN) was developed and the model interpretation at various convolutional layers was systematically analyzed to improve the understanding of how CNN interprets multimodality medical images and the predictive powers of features at each layer. The problem of small sample size was addressed by feeding the intermediate features into a traditional classification algorithm known as weighted extreme learning machine (wELM), with imbalanced distribution among output categories taken into consideration. METHODS: The training data collection used a retrospective set of prostate MR studies, from SPIE-AAPM-NCI PROSTATEx Challenges held in 2017. Three hundred twenty biopsy samples of lesions from 201 prostate cancer patients were diagnosed and identified as clinically significant (malignant) or not significant (benign). All studies included T2-weighted (T2W), proton density-weighted (PD-W), dynamic contrast enhanced (DCE) and diffusion-weighted (DW) imaging. After registration and lesion-based normalization, a CNN with four convolutional layers were developed and trained on tenfold cross validation. The features from intermediate layers were then extracted as input to wELM to test the discriminative power of each individual layer. The best performing model from the tenfolds was chosen to be tested on the holdout cohort from two sources. Feature maps after each convolutional layer were then visualized to monitor the trend, as the layer propagated. Scatter plotting was used to visualize the transformation of data distribution. Finally, a class activation map was generated to highlight the region of interest based on the model perspective. RESULTS: Experimental trials indicated that the best input for CNN was a modality combination of T2W, apparent diffusion coefficient (ADC) and DWIb50 . The convolutional features from CNN paired with a weighted extreme learning classifier showed substantial performance compared to a CNN end-to-end training model. The feature map visualization reveals similar findings on natural images where lower layers tend to learn lower level features such as edges, intensity changes, etc, while higher layers learn more abstract and task-related concept such as the lesion region. The generated saliency map revealed that the model was able to focus on the region of interest where the lesion resided and filter out background information, including prostate boundary, rectum, etc. CONCLUSIONS: This work designs a customized workflow for the small and imbalanced dataset of prostate mpMRI where features were extracted from a deep learning model and then analyzed by a traditional machine learning classifier. In addition, this work contributes to revealing how deep learning models interpret mpMRI for prostate cancer patient stratification.

Real-time Magnetic Resonance-guided Liver Stereotactic Body Radiation Therapy: An Institutional Report Using a Magnetic Resonance-Linac System.

Background Stereotactic body radiation therapy (SBRT) is a proven and effective modality for treatment of hepatic primary and metastatic tumors. However, these lesions are challenging for planning and treatment execution due to natural anatomic changes associated with respiration. Magnetic resonance imaging (MRI) offers superior soft tissue contrast resolution and the ability for real-time image-guided treatment delivery and lesion tracking. Objective To evaluate the plan quality, treatment delivery, and tumor response of a set of liver SBRT cancer treatments delivered with magnetic resonance (MR)-guided radiotherapy on a MR-linear accelerator (MR-linac). Methods Treatment data from 29 consecutive patients treated with SBRT were reviewed. All treatments were performed using a step and shoot technique to one or more liver lesions on an MR-linac platform. Patients received 45 to 50 Gy prescribed to at least 95% of the planning target volume (PTV) in five fractions except for two patients who received 27-30 Gy in three fractions. Computed tomography and MRI simulation were performed in the supine position prior to treatment in the free-breathing, end exhalation, and end inhalation breath-hold positions to determine patient tolerability and potential dosimetric advantages of each technique. Immobilization consisted of using anterior and posterior torso MRI receive coils embedded in a medium-sized vacuum cushion. Gating was performed using sagittal cine images acquired at 4 frames/second. Gating boundaries were defined in the three major axes to be 0.3 to 0.5 cm. An overlapping region of interest, defined as the percentage volume allowed outside the boundary for beam-on to occur, was set between 1 and 10%. The contoured target was assigned a 5-mm PTV expansion. Organs at risk constraints adopted by the American Association of Physicists in Medicine Task Group 101 were used during optimization. Results Twenty-nine patients, with a total of 34 lesions, successfully completed the prescribed treatment with minimal treatment breaks or delays. Twenty-one patients were treated at end-exhale, and six were treated at end-inhale. Two patients were treated using a free-breathing technique due to poor compliance with breath-hold instructions. The reported mean liver dose was 5.56 Gy (1.39 - 10.43; STD 2.85) and the reported mean liver volume receiving the prescribed threshold dose was 103.1 cm3 (2.9 - 236.6; STD 75.2). Follow-up imaging at one to 12 months post treatment confirmed either stable or decreased size of treated lesions in all but one patient. Toxicities were mild and included nausea/vomiting, abdominal pain and one case of bloody diarrhea. Four patients died due to complications from liver cirrhosis unrelated to radiation effect. Conclusion SBRT treatment using a gated technique on an MR-linac has been successfully demonstrated. Potential benefits of this modality include decreased liver dose leading to decreased toxicities. Further studies to identify the benefits and risks associated with MR-guided SBRT are necessary.

Volumetric and Voxel-Wise Analysis of Dominant Intraprostatic Lesions on Multiparametric MRI.

Introduction: Multiparametric MR imaging (mpMRI) has shown promising results in the diagnosis and localization of prostate cancer. Furthermore, mpMRI may play an important role in identifying the dominant intraprostatic lesion (DIL) for radiotherapy boost. We sought to investigate the level of correlation between dominant tumor foci contoured on various mpMRI sequences. Methods: mpMRI data from 90 patients with MR-guided biopsy-proven prostate cancer were obtained from the SPIE-AAPM-NCI Prostate MR Classification Challenge. Each case consisted of T2-weighted (T2W), apparent diffusion coefficient (ADC), and Ktrans images computed from dynamic contrast-enhanced sequences. All image sets were rigidly co-registered, and the dominant tumor foci were identified and contoured for each MRI sequence. Hausdorff distance (HD), mean distance to agreement (MDA), and Dice and Jaccard coefficients were calculated between the contours for each pair of MRI sequences (i.e., T2 vs. ADC, T2 vs. Ktrans, and ADC vs. Ktrans). The voxel wise spearman correlation was also obtained between these image pairs. Results: The DILs were located in the anterior fibromuscular stroma, central zone, peripheral zone, and transition zone in 35.2, 5.6, 32.4, and 25.4% of patients, respectively. Gleason grade groups 1-5 represented 29.6, 40.8, 15.5, and 14.1% of the study population, respectively (with group grades 4 and 5 analyzed together). The mean contour volumes for the T2W images, and the ADC and Ktrans maps were 2.14 ± 2.1, 2.22 ± 2.2, and 1.84 ± 1.5 mL, respectively. Ktrans values were indistinguishable between cancerous regions and the rest of prostatic regions for 19 patients. The Dice coefficient and Jaccard index were 0.74 ± 0.13, 0.60 ± 0.15 for T2W-ADC and 0.61 ± 0.16, 0.46 ± 0.16 for T2W-Ktrans. The voxel-based Spearman correlations were 0.20 ± 0.20 for T2W-ADC and 0.13 ± 0.25 for T2W-Ktrans. Conclusions: The DIL contoured on T2W images had a high level of agreement with those contoured on ADC maps, but there was little to no quantitative correlation of these results with tumor location and Gleason grade group. Technical hurdles are yet to be solved for precision radiotherapy to target the DILs based on physiological imaging. A Boolean sum volume (BSV) incorporating all available MR sequences may be reasonable in delineating the DIL boost volume.

A Matched Analysis on the Prognostic Impact of Race on Survival Endpoints of Women with Early-Stage Endometrial Cancer.

OBJECTIVE: To compare survival endpoints between African American (AA) and non-AA (NAA) women with endometrial carcinoma (EC) stage I-II using a robust matching analysis. METHODS AND MATERIALS: Patients were matched by stage, grade, adjuvant management (surveillance, vaginal brachytherapy or pelvic radiation treatment), age, and year of hysterectomy. Recurrence-free survival (RFS), disease-specific survival (DSS) and overall survival (OS) were calculated. RESULTS: A total of 758 patients were included. Body mass index and Age-Adjusted Charlson comorbidity index was significantly higher in AA compared to NAA women. There were no significant differences between the AA and NAA groups in regard to 5-year RFS (94 vs. 93%), DSS (96 vs. 98%) or 5-year OS (90 vs. 92%). On multivariate analysis of survival endpoints for the entire study cohort, it was found that race (AA vs. NAA) was not a significant predictor of RFS, DSS, or OS. Grade 3 tumors and the presence of lymphovascular space invasion (LVSI) were the only 2 independent predictors of RFS and DSS, while age-adjusted Charlson comorbidity score, grade 3, stage II and the presence of LVSI were independent predictors of shorter OS. CONCLUSIONS: When matched based on the tumor stage, grade, adjuvant treatment, age, and year of surgery, our study suggests that there is no statistically significant difference in any survival endpoints between AA and NAA women with early-stage EC. Based on these data, disparities in outcome likely do not stem from uterine cancer-related causes. The increased comorbidity burden in AA women is likely a factor contributing to the racial disparity in endometrial cancer.

Management of gynaecologic plasmacytoma: A review article.

In contrast to multiple myeloma (MM) which exhibits diffuse bone marrow and other organ involvement, solitary plasmacytomas carry a favourable prognosis. Extramedullary plasmacytomas (EMP) are a unique form of plasma cell neoplasms. These tumours are rare in the female reproductive tract. Only 24 cases of gynaecologic plasmacytomas were reported to date (7 cases were solitary plasmacytomas and 17 cases were either part of disseminated MM with involvement of a gynaecologic organ or were lacking complete work-up to rule out MM). The standard care of gynaecologic solitary EMP is surgical resection alone when feasible. Adjuvant radiation therapy may be considered for adverse prognostic factors such as positive resection margins. MM with gynaecologic organ involvement should be managed with systemic therapy and defer local therapies to symptomatic progression.

The Impact of Adjuvant Therapy on Survival and Recurrence Patterns in Women With Early-Stage Uterine Carcinosarcoma: A Multi-institutional Study.

OBJECTIVE: The aim of the study was to characterize the impact of adjuvant therapy on survival in women with stage I/II uterine carcinosarcoma after primary surgery. METHODS: We reviewed records of 118 consecutively treated women with 2009 International Federation of Gynecology and Obstetrics stage I/II uterine carcinosarcoma who underwent hysterectomy between 1990 and 2014 at 4 academic institutions. Patients were categorized by adjuvant treatment group into observation, chemotherapy only, radiation only, and combined chemotherapy and radiation. Survival analyses were conducted using Kaplan-Meier and Cox proportional hazards models. RESULTS: Median follow-up was 28 months (range, 1-244 months). Lymphadenectomy was performed in 94 patients (80%). Postoperative management included observation (n = 37 [31%]), chemotherapy alone (n = 19 [16%]), radiation therapy (RT) alone (n = 24 [20%]), and combined RT and chemotherapy (n = 38 [32%]). Radiation therapy modality included vaginal brachytherapy in 22 patients, pelvic external beam RT in 21 patients, and combination in 19 patients. In 58% of women, chemotherapy consisted of carboplatin/paclitaxel. Median overall survival for all women was 97 months. On univariate analysis, adjuvant treatment group was associated with improved overall survival (hazard ratio [HR], 0.74; confidence interval [CI], 0.58-0.96; p = 0.02), freedom from vaginal recurrence (HR, 0.55; CI, 0.37-0.82]; p = 0.004), and freedom from any recurrence (HR, 0.70; CI, 0.54-0.92; p = 0.01). Pairwise comparisons demonstrated a significant benefit to chemoradiation over other adjuvant treatments. Adjuvant treatment group remained a significant covariate for all 3 end points on multivariate analysis as well. In addition, lymphadenectomy improved overall survival on multivariate analysis (HR, 0.24; CI, 0.09-0.61; p = 0.003). Of patients under observation only who had a recurrence, 8 (44%) of 18 had a recurrence in the vagina as the sole site of recurrence. By contrast, of women who received vaginal brachytherapy, significantly fewer had a recurrence in the vagina (1/42 [2.3%]; p < 0.003, log-rank test). CONCLUSIONS: In women with early-stage uterine carcinosarcoma, our data suggest superior survival end points with combined RT and chemotherapy. The frequency of vaginal recurrence suggests a role for incorporating vaginal brachytherapy in the adjuvant management of this disease.

Solitary ovarian plasmacytoma. A case report and review of literature.

•A patient with rare solitary ovarian plasmacytoma is reported•Diagnostic work-up is mandatory to rule out ovarian involvement as part of multiple myeloma.•After complete surgical resection, the prognosis appears to be very favorable.

Clinical utility of a polymerase chain reaction assay in culture-negative necrotizing otitis externa.

OBJECTIVE: This study describes a subset of necrotizing otitis externa (NOE) patients with a refractory disease and negative cultures. In these cases, we decided to use a polymerase chain reaction (PCR) assay from surgically obtained tissue under sterile conditions to improve pathogen detection sensitivity. STUDY DESIGN: Retrospective case review. SETTING: Academic medical center. PATIENTS: Nineteen consecutive patients diagnosed with NOE between January 2008 and January 2014 inclusive. Three patients of this cohort presented a culture-negative disease. INTERVENTIONS: Diagnostic. MAIN OUTCOME MEASURES: Positive detection of pathogens using a PCR assay in cases with a complicated course of NOE and clinical resolution of the disease after targeted therapy according to PCR results. RESULTS: Surgical samples were obtained under sterile conditions from three patients with negative cultures and a refractory disease course of NOE. PCR assays were performed using pan-bacteria and pan-fungi protocols. In all three samples, a positive result for a fungal pathogen was recorded and followed by successful empirical targeted therapy. CONCLUSION: Patients who present with a refractory culture-negative NOE should be suspected as suffering from a fungal disease. The PCR assay may be an important laboratory adjunct in detecting pathogens responsible for NOE and can aid to promote therapy and disease resolution.