Radiomics for Response and Outcome Assessment for Non-Small Cell Lung Cancer.

Routine follow-up visits and radiographic imaging are required for outcome evaluation and tumor recurrence monitoring. Yet more personalized surveillance is required in order to sufficiently address the nature of heterogeneity in nonsmall cell lung cancer and possible recurrences upon completion of treatment. Radiomics, an emerging noninvasive technology using medical imaging analysis and data mining methodology, has been adopted to the area of cancer diagnostics in recent years. Its potential application in response assessment for cancer treatment has also drawn considerable attention. Radiomics seeks to extract a large amount of valuable information from patients' medical images (both pretreatment and follow-up images) and quantitatively correlate image features with diagnostic and therapeutic outcomes. Radiomics relies on computers to identify and analyze vast amounts of quantitative image features that were previously overlooked, unmanageable, or failed to be identified (and recorded) by human eyes. The research area has been focusing on the predictive accuracy of pretreatment features for outcome and response and the early discovery of signs of tumor response, recurrence, distant metastasis, radiation-induced lung injury, death, and other outcomes, respectively. This review summarized the application of radiomics in response assessments in radiotherapy and chemotherapy for non-small cell lung cancer, including image acquisition/reconstruction, region of interest definition/segmentation, feature extraction, and feature selection and classification. The literature search for references of this article includes PubMed peer-reviewed publications over the last 10 years on the topics of radiomics, textural features, radiotherapy, chemotherapy, lung cancer, and response assessment. Summary tables of radiomics in response assessment and treatment outcome prediction in radiation oncology have been developed based on the comprehensive review of the literature

Converting Treatment Plans From Helical Tomotherapy to L-Shape Linac: Clinical Workflow and Dosimetric Evaluation.

This work evaluated a commercial fallback planning workflow designed to provide cross-platform treatment planning and delivery. A total of 27 helical tomotherapy intensity-modulated radiotherapy plans covering 4 anatomical sites were selected, including 7 brain, 5 unilateral head and neck, 5 bilateral head and neck, 5 pelvis, and 5 prostate cases. All helical tomotherapy plans were converted to 7-field/9-field intensity-modulated radiotherapy and volumetric-modulated radiotherapy plans through fallback dose-mimicking algorithm using a 6-MV beam model. The planning target volume (PTV) coverage ( D1, D99, and homogeneity index) and organs at risk dose constraints were evaluated and compared. Overall, all 3 techniques resulted in relatively inferior target dose coverage compared to helical tomotherapy plans, with higher homogeneity index and maximum dose. The organs at risk dose ratio of fallback to helical tomotherapy plans covered a wide spectrum, from 0.87 to 1.11 on average for all sites, with fallback plans being superior for brain, pelvis, and prostate sites. The quality of fallback plans depends on the delivery technique, field numbers, and angles, as well as user selection of structures for organs at risk. In actual clinical scenario, fallback plans would typically be needed for 1 to 5 fractions of a treatment course in the event of machine breakdown. Our results suggested that <1% dose variance can be introduced in target coverage and/or organs at risk from fallback plans. The presented clinical workflow showed that the fallback plan generation typically takes 10 to 20 minutes per case. Fallback planning provides an expeditious and effective strategy for transferring patients cross platforms, and minimizing the untold risk of a patient missing treatment(s)

A Cone Beam CT-Based Study For Clinical Target Definition Using Pelvic Anatomy During Post-Prostatectomy Radiotherapy

Introduction: Radiation therapy (RT) is delivered after radical prostatectomy (RP) either as salvage treatment for an elevated prostate-specific antigen (PSA) level1-6 or as adjuvant therapy for patients with highrisk pathologic features7-8. Recent prospective data demonstrated a disease-free survival benefit of adjuvant RT for pathologic T3N0 prostate cancer9-10. Despite literature supporting the delivery of post-RP RT to the prostatic fossa (PF), no clear target definition guidelines exist for intensity modulated radiation therapy (IMRT) or image-guided RT (IGRT)11. Visualization of the PF is limited on standard CT images, with significant interobserver variability and uncertainty in CTV definition12. Efforts to incorporate complementary imaging modalities such as MRI for PF target volume definition have generated neither demonstrably more reliable PF delineation, nor practical contouring guidelines13. Regardless of the imaging modality, direct visualization and delineation of the PF clinical target volume (CTV) is fraught with uncertainty. On the other hand, it is possible to distinguish the borders of important nearby pelvic structures, namely the bladder and the rectum. The reliability of rectal volume definition on helical CT is supported by analysis of rectal contours defined in a prospective trial, suggesting the feasibility of rectal dose-volume data collection in a multicenter setting14. Fiorino et al have described a correlation between PF CTV shift and anterior rectal wall shift for the cranial half of the rectum in their report of rectal and bladder movement during post-RP RT using weekly CT images15. These studies support the reliability of CT-defined rectum contours and a limited correlation between PF CTV and anterior rectal wall, an important tenet in the current study. Int. J. Radiation Oncol. Biol. Physics, Volume 70, Issue 2, pages 431-436, Feb. 1, 2008

First Report of NRG Oncology/Radiation Therapy Oncology Group 0622: A Phase 2 Trial of Samarium-153 Followed by Salvage Prostatic Fossa Irradiation in High-Risk Clinically Nonmetastatic Prostate Cancer After Radical Prostatectomy.

PURPOSE: To investigate the utility of 153Sm lexidronam (Quadramet) in the setting of men with prostate cancer status post radical prostatectomy who develop biochemical failure with no clinical evidence of osseous metastases. PATIENTS AND METHODS: Trial NRG Oncology RTOG 0622 is a single-arm phase 2 trial that enrolled men with pT2-T4, N0-1, M0 prostate cancer status post radical prostatectomy, who meet at least 1 of these biochemical failure criteria: (1) prostate-specific antigen (PSA) \u3e 1.0 ng/mL; (2) PSA \u3e 0.2 ng/mL if Gleason score 9 to 10; or (3) PSA \u3e 0.2 ng/mL if N1. Patients received 153Sm (2.0 mCi/kg intravenously × 1) followed by salvage external beam radiation therapy (EBRT) to the prostatic fossa (64.8-70.2 Gy in 1.8-Gy daily fractions). No androgen deprivation therapy was allowed. The primary objective was PSA response within 12 weeks of receiving 153Sm. The secondary objectives were to: (1) assess the completion rate for the regimen of 153Sm and EBRT; (2) evaluate the hematologic toxicity and other adverse events (AEs) at 12 and 24 weeks; and (3) determine the freedom from progression rate at 2 years. RESULTS: A total of 60 enrolled eligible patients were included in this analysis. Median follow-up was 3.97 years. A PSA response was achieved in 7 of 52 evaluable patients (13.5%), compared with the 25% hypothesized. The 2-year freedom from progression rate was 25.5% (95% confidence interval 14.4%-36.7%), and the biochemical failure rate was 64.4% (95% CI 50.5%-75.2%). Samarium-153 was well tolerated, with 16 (of 60) grade 3 to 4 hematologic AEs and no grade 5 hematologic AEs. Radiation therapy was also well tolerated, with no grade 3 to 5 acute radiation therapy-related AEs and 1 grade 3 to 4 and no grade 5 late radiation therapy-related AEs. CONCLUSIONS: Trial NRG Oncology RTOG 0622 did not meet its primary endpoint of PSA response, although the regimen of 153Sm and salvage EBRT was well tolerated. Although the toxicity profile supports study of 153Sm in high-risk disease, it may not be beneficial in men receiving EBRT

Mitochondrial Disease in Autism Spectrum Disorder Patients: A Cohort Analysis

Previous reports indicate an association between autism spectrum disorders (ASD) and disorders of mitochondrial oxidative phosphorylation. One study suggested that children with both diagnoses are clinically indistinguishable from children with idiopathic autism. There are, however, no detailed analyses of the clinical and laboratory findings in a large cohort of these children. Therefore, we undertook a comprehensive review of patients with ASD and a mitochondrial disorder.We reviewed medical records of 25 patients with a primary diagnosis of ASD by DSM-IV-TR criteria, later determined to have enzyme- or mutation-defined mitochondrial electron transport chain (ETC) dysfunction. Twenty-four of 25 patients had one or more major clinical abnormalities uncommon in idiopathic autism. Twenty-one patients had histories of significant non-neurological medical problems. Nineteen patients exhibited constitutional symptoms, especially excessive fatigability. Fifteen patients had abnormal neurological findings. Unusual developmental phenotypes included marked delay in early gross motor milestones (32%) and unusual patterns of regression (40%). Levels of blood lactate, plasma alanine, and serum ALT and/or AST were increased at least once in 76%, 36%, and 52% of patients, respectively. The most common ETC disorders were deficiencies of complex I (64%) and complex III (20%). Two patients had rare mtDNA mutations of likely pathogenicity.Although all patients' initial diagnosis was idiopathic autism, careful clinical and biochemical assessment identified clinical findings that differentiated them from children with idiopathic autism. These and prior data suggest a disturbance of mitochondrial energy production as an underlying pathophysiological mechanism in a subset of individuals with autism

Adjuvant and Salvage Radiotherapy after Prostatectomy: ASTRO/AUA Guideline Amendment 2018-2019.

PurposeThe purpose of this amendment is to incorporate newly-published literature into the original ASTRO/AUA Adjuvant and Salvage Radiotherapy after Prostatectomy Guideline and to provide an updated clinical framework for clinicians.Materials and methodsThe original systematic review yielded 294 studies published between January 1990 and December 2012. In April 2018, the guideline underwent an amendment and incorporated 155 references that were published from January 1990 through December 2017. Two new key questions were added. One on the use of genomic classifiers and the other on the treatment of oligo-metastases with radiation post-radical prostatectomy.ResultsA new statement on the use of hormone therapy with salvage radiotherapy after radical prostatectomy was added and long-term data was used to update an existing statement on adjuvant radiotherapy. The balance of the guideline statements were re-affirmed and references were added to the existing literature base. A discussion on the use of genomic classifiers as a risk stratification tool was added to the future research discussion. No relevant data on oligo-metastases was found.ConclusionsHormone therapy should be offered to patients who have had radical prostatectomy and who are candidates for salvage radiotherapy. The clinician should discuss possible short- and long-term side effects with the patient as well as the potential benefits of preventing recurrence. The decision to use hormone therapy should be made by the patient and a multi-disciplinary team of providers with full consideration of the patient's history, values, preferences, quality of life, and functional status