No Oncology Patient Left Behind: Challenges and Solutions in Rural Radiation Oncology.

Health inequities and decreasing median American lifespan, potentiated by the worldwide COVID 19 crisis, have taken centre stage in the public consciousness. Specifically, for this discourse, rural radiation oncology challenges external to the pandemic and unique to the rural American radiation oncology care delivery result from a confluence of the following: a) increased incidence of cancer in the United States;1 b) recent legislative emphasis on rural healthcare equity initiatives;2 c) pandemic-associated delays in cancer screening, diagnosis, and treatment3 , 4 with resultant presentation of advanced oncologic stages; d) social spotlight on healthcare equity and inclusion for disenfranchised populations.5We will attempt to delineate these issues and propose widely applicable common-sense solutions. We will review what has transpired at the University of Kentucky over the last two decades, specifically at radiation oncology centre in Morehead, a clinic in eastern Kentucky in the Appalachian foothills. While much more work remains ahead, this clinic has successfully applied many of the initiatives discussed. Funding: No relevant funding of any research was involved in the preparation of data or the manuscript.

Aneurysmal Fibrous Histiocytoma: A Large Soft Tissue Tumor with Metastases Treated with Palliative Radiation Therapy and Targeted Therapy.

Aneurysmal fibrous histiocytoma (AFH) is a rare variant of cutaneous fibrous histiocytoma, with low malignant potential and infrequent metastatic progression. We present the case of a 19-year-old female with a large AFH of the neck metastatic to soft tissue and treated with radiation therapy and molecularly targeted therapy. To our knowledge, this is the first report describing either radiation therapy and palliation or the use of targeted therapy in this uncommon malignancy and can provide insight into future therapeutic strategies.

A phase I trial of lenalidomide and radiotherapy in children with diffuse intrinsic pontine gliomas or high-grade gliomas.

PURPOSE: This study was performed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of the immunomodulatory agent, lenalidomide, when administered daily during 6 weeks of radiation therapy to children with newly diagnosed diffuse intrinsic pontine glioma (DIPG) or high-grade glioma (HGG) PATIENTS & METHODS: Children and young adults < 22 years of age with newly diagnosed disease and no prior chemotherapy or radiation therapy were eligible. Children with HGG were required to have an inoperable or incompletely resected tumor. Eligible patients received standard radiation therapy to a prescription dose of 54-59.4 Gy, with concurrent administration of lenalidomide daily during radiation therapy in a standard 3 + 3 Phase I dose escalation design. Following completion of radiation therapy, patients had a 2-week break followed by maintenance lenalidomide at 116 mg/m2/day × 21 days of a 28-day cycle. RESULTS: Twenty-nine patients (age range 4-19 years) were enrolled; 24 were evaluable for dose finding (DIPG, n = 13; HGG, n = 11). The MTD was not reached at doses of lenalidomide up to 116 mg/m2/day. Exceptional responses were noted in DIPG and malignant glioma (gliomatosis cerebri) notably at higher dose levels and at higher steady state plasma concentrations. The primary toxicity was myelosuppression. CONCLUSION: The RP2D of lenalidomide administered daily during radiation therapy is 116 mg/m2/day. Children with malignant gliomas tolerate much higher doses of lenalidomide during radiation therapy compared to adults. This finding is critical as activity was observed primarily at higher dose levels suggesting a dose response.

Multiparametric MRI for the detection of local recurrence of prostate cancer in the setting of biochemical recurrence after low dose rate brachytherapy.

PURPOSE: Prostate multiparametric magnetic resonance imaging (mpMRI) has utility in detecting post-radiotherapy local recurrence. We conducted a multireader study to evaluate the diagnostic performance of mpMRI for local recurrence after low dose rate (LDR) brachytherapy. METHODS: A total of 19 patients with biochemical recurrence after LDR brachytherapy underwent 3T endorectal coil mpMRI with T2-weighted imaging, dynamic contrast-enhanced imaging (DCE) and diffusion-weighted imaging (DWI) with pathologic confirmation. Prospective reads by an experienced prostate radiologist were compared with reads from 4 radiologists of varying experience. Readers identified suspicious lesions and rated each MRI detection parameter. MRI-detected lesions were considered true-positive with ipsilateral pathologic confirmation. Inferences for sensitivity, specificity, positive predictive value (PPV), kappa, and index of specific agreement were made with the use of bootstrap resampling. RESULTS: Pathologically confirmed recurrence was found in 15 of 19 patients. True positive recurrences identified by mpMRI were frequently located in the transition zone (46.7%) and seminal vesicles (30%). On patient-based analysis, average sensitivity of mpMRI was 88% (standard error [SE], 3.5%). For highly suspicious lesions, specificity of mpMRI was 75% (SE, 16.5%). On lesion-based analysis, the average PPV was 62% (SE, 6.7%) for all lesions and 78.7% (SE, 10.3%) for highly suspicious lesions. The average PPV for lesions invading the seminal vesicles was 88.8% (n=13). The average PPV was 66.6% (SE, 5.8%) for lesions identified with T2-weighted imaging, 64.9% (SE, 7.3%) for DCE, and 70% (SE, 7.3%) for DWI. CONCLUSION: This series provides evidence that mpMRI after LDR brachytherapy is feasible with a high patient-based cancer detection rate. Radiologists of varying experience demonstrated moderate agreement in detecting recurrence.

Effect of Prostate Magnetic Resonance Imaging/Ultrasound Fusion-guided Biopsy on Radiation Treatment Recommendations.

PURPOSE: Targeted magnetic resonance imaging (MRI)/ultrasound fusion prostate biopsy (MRI-Bx) has recently been compared with the standard of care extended sextant ultrasound-guided prostate biopsy (SOC-Bx), with the former associated with an increased rate of detection of clinically significant prostate cancer. The present study sought to determine the influence of MRI-Bx on radiation therapy and androgen deprivation therapy (ADT) recommendations. METHODS AND MATERIALS: All patients who had received radiation treatment and had undergone SOC-Bx and MRI-Bx at our institution were included. Using the clinical T stage, pretreatment prostate-specific antigen, and Gleason score, patients were categorized into National Comprehensive Cancer Network risk groups and radiation treatment or ADT recommendations assigned. Intensification of the recommended treatment after multiparametric MRI, SOC-Bx, and MRI-Bx was evaluated. RESULTS: From January 2008 to January 2016, 73 patients received radiation therapy at our institution after undergoing a simultaneous SOC-Bx and MRI-Bx (n=47 with previous SOC-Bx). Repeat SOC-Bx and MRI-Bx resulted in frequent upgrading compared with previous SOC-Bx (Gleason score 7, 6.7% vs 44.6%; P<.001; Gleason score 8-10, 2.1% vs 38%; P<.001). MRI-Bx increased the proportion of patients classified as very high risk from 24.7% to 41.1% (P=.027). Compared with SOC-Bx alone, including the MRI-Bx findings resulted in a greater percentage of pathologically positive cores (mean 37% vs 44%). Incorporation of multiparametric MRI and MRI-Bx results increased the recommended use and duration of ADT (duration increased in 28 of 73 patients and ADT was added for 8 of 73 patients). CONCLUSIONS: In patients referred for radiation treatment, MRI-Bx resulted in an increase in the percentage of positive cores, Gleason score, and risk grouping. The benefit of treatment intensification in accordance with the MRI-Bx findings is unknown.

Optimizing the Benefit of CNS Radiation Therapy in the Pediatric Population-PART 1: Understanding and Managing Acute and Late Toxicities.

Radiation therapy continues to be a key component in the management of pediatric malignancies. Increasing the likelihood of cure while minimizing late treatment toxicity in these young patients remains the primary goal. Within the realm of central nervous system neoplasms, efforts to further improve the efficacy of radiation therapy continue, while balancing risks of damage to uninvolved tissue. Radiation therapy can result in second malignancies, as well as cerebrovascular, neurotoxic, neurocognitive, endocrine, psychosocial, and quality-of-life effects. In this article we describe these acute and late effects and their implications, and we highlight strategies that have emerged to reduce both the volume of tissue that is irradiated and the radiation dose delivered. The feasibility, efficacy, and risks of these newer approaches to radiation therapy continue to be evaluated and monitored; robust outcome data are needed.

Optimizing the Benefit of CNS Radiation Therapy in the Pediatric Population-PART 2: Novel Methods of Radiation Delivery.

Newer approaches in the field of radiation therapy have raised the bar in the treatment of central nervous system (CNS) malignancies, with recognized advances that have aimed to increase the therapeutic index by improving conformality of the radiation dose to the planned target volume. Beyond these advances, the continued evolution of more effective systems for delivery of radiation to the CNS may offer further benefit not only to adults but also to pediatric patients, a cohort of the population that may be more sensitive to the long-term effects of radiation. This article describes several novel irradiation techniques under investigation that hold promise in the pediatric population. These include newer approaches to intensity-modulated radiation therapy; stereotactic radiosurgery and radiation therapy; particle therapy, most notably proton therapy, which may be of particular benefit in enabling young patients to avoid radiation-related adverse effects; and radioimmunotherapy strategies that spare healthy tissue from radiotoxicity by delivering therapy directly to tumor tissue. Although emerging strategies for the delivery of radiation therapy hold promise for improved outcomes in pediatric patients, there must be rigorous long-term evaluation of consequences associated with the various techniques employed, to weigh risks, benefits, and impact on quality of life.

Clinical Predictors of Fatigue in Men With Non-Metastatic Prostate Cancer Receiving External Beam Radiation Therapy.

BACKGROUND: Fatigue is one of the most distressing symptoms experienced by people with cancer receiving radiation therapy. OBJECTIVES: The goal of this study is to evaluate clinical predictors of worsening fatigue during external beam radiation therapy (EBRT) in men with non-metastatic prostate cancer. METHODS: Thirty-five men with non-metastatic prostate cancer scheduled for EBRT were followed at baseline, midpoint, and completion of EBRT. The Functional Assessment of Cancer Therapy-Fatigue scale was administered. Demographic and clinical data were obtained by chart review. Paired t-tests, correlations, general linear models, and logistic regressions were used to determine associations between fatigue scores and clinical data. FINDINGS: Red blood cells, hemoglobin, and hematocrit levels were highly intercorrelated and, therefore, were grouped as one composite variable termed heme. Heme levels at baseline and androgen-deprivation therapy (ADT) were significantly correlated with worsening of fatigue symptoms from baseline to midpoint and endpoint. ADT alone did not have a significant correlation with fatigue, but it indirectly affected fatigue levels by influencing heme markers as treatment progressed. These findings provide evidence that hematologic markers and the use of ADT assist in predicting radiation therapy-related fatigue and guide symptom management.

Multiparametric magnetic resonance imaging-transrectal ultrasound fusion-assisted biopsy for the diagnosis of local recurrence after radical prostatectomy.

OBJECTIVE: Approximately 15% of patients who undergo radical prostatectomy (RP) for prostate cancer develop local recurrence, which is heralded by a rise in serum prostate-specific antigen (PSA) levels. Early detection and treatment of recurrence improves the outcome of salvage treatment. We investigated the ability of multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion-guided biopsy (FGB) combined with "cognitive biopsy" to confirm local recurrence of prostate cancer after RP. MATERIALS AND METHODS: In this retrospective study conducted between January 2010 and December 2014, patients with rising PSA levels after RP who had no known evidence of distant metastases underwent mpMRI including T2-weighted (T2W) imaging, diffusion-weighted imaging, dynamic contrast-enhanced (DCE) MRI at 3 Tesla, and subsequent MRI-ultrasound fusion biopsy with cognitive assistance. The detection rate of locally recurrent disease was determined. RESULTS: A total of 10 patients (mean age = 67y, mean PSA level = 3.44ng/ml) met the inclusion criteria. Of the 10 patients, all had positive findings suspicious for local recurrence on mpMRI per entrance criterion. The most important features on mpMRI were early enhancement on DCE MR images and hypointensity on T2W images. The average lesion diameter on mpMRI was 1.12cm (range: 0.40-2.20cm). All suspicious lesions (16/16, 100%) were positive on T2W MR images, 14 (89%) showed positive features on apparent diffusion coefficient maps of diffusion-weighted images, and 16 (100%) were positive on DCE MR images. MRI-TRUS FGBs were positive in 10/16 lesions (62.5%) and 8/10 (80%) patients. CONCLUSION: MRI-TRUS FGB with cognitive assistance is able to detect and diagnose locally recurrent lesions after RP, even at low PSA levels. This may facilitate early detection of recurrent disease and improve salvage treatment outcomes.

Primary Treatment Options for High-Risk/Medically Inoperable Early Stage NSCLC Patients.

Lung cancer is among the most common cancers worldwide and is the leading cause of cancer death in both men and women. For patients with early stage (American Joint Committee on Cancer T1-2, N0) non-small-cell lung cancer, the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, patients with lung cancer often have medical comorbities, which may preclude the option of surgical resection. In such cases, a number of minimally invasive to noninvasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages, including patient convenience, treatment in an outpatient setting, and acceptable toxicities, including reduced impact on lung function and a modest risk of postprocedure chest wall pain. We provide a comprehensive review of the literature, including reported outcomes, complications, and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy, and stereotactic body radiotherapy.

Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.

INTRODUCTION: Malignant peripheral nerve sheath tumors (MPNSTs) are highly aggressive soft tissue sarcomas in which complete surgical resection is the mainstay of therapy. However, the recurrence rate is high and few options remain for refractory or metastatic MPNST. This study examines the outcomes of adjuvant radiation therapy in MPNST in patients with and without neurofibromatosis type 1 (NF1) and reviews the literature on use of radiation for MPNST. METHODS: A retrospective review of 33 MPNST patients between 1990 and 2012 evaluated at the NIH. All diagnoses were pathologically confirmed at the NCI. Clinical presentation, treatment, and survival were analyzed. RESULTS: Thirty-three patients were included 18 NF1-associated, 15 sporadic tumors. Tumor location included extremity (58%), trunk (36%), and head/neck (6%). Histologic grade showed 25 high-grade tumors compared to 7 low-grade tumors. Twenty patients were treated with radiation therapy (median total dose of 58.5 Gy with 1.8 Gy/fraction). A median survival of all patients was 46.5 months and 43.7% overall 5-year survival. Prognostic factors include extent of resection, tumor location, and histology grade. Radiation was not found to be a prognostic factor for overall survival. CONCLUSION: This study is consistent with previous studies regarding the role of radiation in the management of MPNST. Prospective evaluation of adjuvant radiation will allow to more fully define the role of radiation in MPNST.

External beam radiation therapy in treatment of malignant pheochromocytoma and paraganglioma.

PURPOSE: Pheochromocytomas (PCCs) are neuroendocrine tumors arising from the adrenal medulla or as paraganglioma (PGL) from extra-adrenal sites. While usually benign, a small fraction is malignant. Multi-modality therapy is used in treating malignant disease; however, little data exist on the role of external beam radiation therapy (EBRT). In this retrospective review, we assessed response to EBRT in malignant PCCs or PGLs. METHODS AND MATERIALS: Records of patients treated at the National Institutes of Health who received EBRT between 1990 and 2012 were studied. Patients were assessed for symptomatic control, biochemical response, local and distant control by response evaluation criteria in solid tumors v1.1 or stable disease on imaging reports, toxicity by radiation therapy oncology group (RTOG) criteria, and survival. RESULTS: There were 24 patients treated who received EBRT to lesions of the abdomen (n = 3), central nervous system (n = 4), and bone (n = 40). Lesions were treated with 3D conformal EBRT to a mean dose of 31.8 Gy in 3.3 Gy fractions, or fractionated stereotactic radiosurgery to 21.9 Gy in 13.6 Gy fractions. Patients experienced acute (n = 15) and late (n = 2) RTOG toxicities; no patient experienced acute toxicity ≥4 or late toxicity ≥2. Symptomatic control was achieved in 81.1% of lesions. Stable radiographic response was achieved in 86.7% of lesions with progression in 13%. Distant progression was observed overall in 75% of patients and average survival was 52.4 months. CONCLUSION: Malignant PCC and PGL often do not respond well to current systemic therapies. In these cases, EBRT can be considered in patients with symptomatic, localized disease progression.

Differential expression of genes related to mitochondrial biogenesis and bioenergetics in fatigued prostate cancer men receiving external beam radiation therapy.

OBJECTIVES: This prospective study explored relationships between expression changes of genes related to mitochondrial biogenesis/bioenergetics and fatigue in men with prostate cancer receiving external beam radiation therapy (EBRT). METHODS: Fatigue and gene expression were measured before (Day 0), at midpoint (Days 19-21), and at completion (Days 38-42) of EBRT using the seven-item Patient-Reported Outcomes Measurement Information System-Fatigue short form and from whole blood cell RNA, respectively. The human mitochondria RT2 Profiler PCR Array System was used to identify differential expression of mitochondrial biogenesis/bioenergetics-related genes. Mixed linear modeling estimated the changes in fatigue and gene expression over time and determined significant associations between gene expression and fatigue. RESULTS: Subjects were 50 men with prostate cancer (scheduled for EBRT = 25, active surveillance as matched controls = 25). The mean Patient-Reported Outcomes Measurement Information System-Fatigue T-score (mean = 50 ± 10 in a general population) for study subjects was 44.87 ± 5.89 and for controls was 43.5 ± 2.8 at baseline. Differential expression of two genes inside the mitochondria involved in critical mitochondrial complexes: BCS1L (ß = 1.30), SLC25A37 (ß = -2.44), and two genes on the outer mitochondrial membrane vital for mitochondrial integrity: BCL2L1 (ß = -1.68) and FIS1 (ß = -2.35) were significantly associated with changes in fatigue scores of study subjects during EBRT. CONCLUSION: Genes related to oxidative phosphorylation, energy production, and mitochondrial membrane integrity are associated with worsening fatigue during EBRT. Further investigation of the pathways involved with this association may explain mechanisms behind the development of fatigue in this population.

Urinary aHGF, IGFBP3 and OPN as diagnostic and prognostic biomarkers for prostate cancer.

AIM: Serum PSA screening for prostate cancer (PCa) is controversial. Here, we identify three urinary biomarkers - aHGF, IGFBP3 and OPN - for PCa screening and prognostication. METHODS: Urinary aHGF, OPN and IGFBP3 from healthy men (n = 19) and men with localized (n = 65) and metastatic (n = 36) PCa were quantified via ELISA. Mann-Whitney nonparametric t-test and the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) analyses were used to analyze associations. RESULTS: Mean aHGF and IGFBP3 levels were significantly elevated in PCa patients versus controls (p = 0.0006 and p = 0.0012, respectively), and the area under the curve of the receiver operating characteristic curve (indicator of diagnostic accuracy) for aHGF and IGFBP3 was 0.75 and 0.74, respectively. OPN levels were significantly higher in metastatic groups (p = 0.0060) versus localized and controls (area under the curve = 0.68). CONCLUSION: Urinary aHGF and IGFBP3 exhibit the capacity for diagnostic discrimination for PCa, whereas OPN may indicate presence of metastatic disease.

Role of radiotherapy in adrenocortical carcinoma.

PURPOSE: Adrenocortical carcinoma (ACC) is a rare and highly malignant tumor usually diagnosed in an advanced stage. Radiation therapy has been a poorly studied and underutilized therapeutic option. METHODS: This retrospective analysis reviewed treatment courses for 14 patients with pathologically confirmed ACC treated between 1997 and 2012. Two patients were treated adjuvantly following surgery, and 12 were treated with palliative intent. Patients presented with stage II (n = 4), stage III (n = 7), and stage IV (n = 3) disease. Patients had a mean age of 51.5 years. Ten patients received chemotherapy before radiotherapy (RT), and 12 patients received surgery before RT, before receiving radiation at a mean of 17.8 months after diagnosis. RESULTS: In total, 20 sites were treated, 2 of which were in an adjuvant setting, and 18 of which were for palliative indications in 12 patients as follows: (1) pain/neuropathy (n = 10), (2) prophylactic treatment of asymptomatic recurrences (n = 3), and (3) prevention of imminent metastatic complications (n = 2), hemoptysis (n = 1), severe mass effect (n = 1), and brain metastasis (n = 1). Sites were treated to a median dose of 36.3 Gy (range, 17.5-60 Gy) in a median of 2.5 Gy/fraction (range, 1.8-4 Gy). At a mean follow-up of 22.0 months for the 2 patients given adjuvant RT, 1 patient did not have a local recurrence during a 14.3-month period of follow-up, and the other had a local recurrence 14.5 months after RT. At a mean follow-up of 11.3 months for the 12 patients receiving palliative RT, 10 patients had either a clinical or radiographic response. Of the courses of palliative RT that had adequate radiographic follow-up, 4 treatments (27%) resulted in a partial response. Eleven treatments (73%) that were able to be evaluated resulted in clinical improvement. Acute Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicities observed in 7 patients included 3 grade 1, 4 grade 2, and 1 grade 3. No patient had acute toxicity of grade 4 or greater or any Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer late toxicity of grade 1 or greater. DISCUSSION: This report is one of the largest to date examining the role of modern radiation techniques in the management of ACC. We conclude that radiation can be effective in the management of metastatic ACC, palliating local symptoms, and preventing complications from large metastases. Radiation should be considered as an option in multimodality management of ACC patients.

Prostate cancer: can multiparametric MR imaging help identify patients who are candidates for active surveillance?

PURPOSE: To determine whether multiparametric magnetic resonance (MR) imaging can help identify patients with prostate cancer who would most appropriately be candidates for active surveillance (AS) according to current guidelines and to compare the results with those of conventional clinical assessment scoring systems, including the D'Amico, Epstein, and Cancer of the Prostate Risk Assessment (CAPRA) systems, on the basis of findings at prostatectomy. MATERIALS AND METHODS: This institutional review board-approved HIPAA-compliant retrospectively designed study included 133 patients (mean age, 59.3 years) with a mean prostate-specific antigen level of 6.73 ng/mL (median, 4.39 ng/mL) who underwent multiparametric MR imaging at 3.0 T before radical prostatectomy. Informed consent was obtained from all patients. Patients were then retrospectively classified as to whether they would have met AS eligibility criteria or were better served by surgery. AS eligibility criteria for prostatectomy specimens were a dominant tumor smaller than 0.5 mL without Gleason 4 or 5 patterns or extracapsular or seminal vesicle invasion. Conventional clinical assessment scores (the D'Amico, Epstein, and CAPRA scoring systems) were compared with multiparametric MR imaging findings for predicting AS candidates. The level of significance of difference between scoring systems was determined by using the χ(2) test for categoric variables with the level of significance set at P < .05. RESULTS: Among 133 patients, 14 were eligible for AS on the basis of prostatectomy results. The sensitivity, positive predictive value (PPV), and overall accuracy, respectively, were 93%, 25%, and 70% for the D'Amico system, 64%, 45%, and 88% for the Epstein criteria, and 93%, 20%, and 59% for the CAPRA scoring system for predicting AS candidates (P < .005 for all, χ(2) test), while multiparametric MR imaging had a sensitivity of 93%, a PPV of 57%, and an overall accuracy of 92% (P < .005). CONCLUSION: Multiparametric MR imaging provides useful additional information to existing clinicopathologic scoring systems of prostate cancer and improves the assignment of treatment (eg, AS or active treatment).

Accuracy analysis in MRI-guided robotic prostate biopsy.

PURPOSE: To assess retrospectively the clinical accuracy of an magnetic resonance imaging-guided robotic prostate biopsy system that has been used in the US National Cancer Institute for over 6 years. METHODS: Series of 2D transverse volumetric MR image slices of the prostate both pre (high-resolution T2-weighted)- and post (low-resolution)- needle insertions were used to evaluate biopsy accuracy. A three-stage registration algorithm consisting of an initial two-step rigid registration followed by a B-spline deformable alignment was developed to capture prostate motion during biopsy. The target displacement (distance between planned and actual biopsy target), needle placement error (distance from planned biopsy target to needle trajectory), and biopsy error (distance from actual biopsy target to needle trajectory) were calculated as accuracy assessment. RESULTS: A total of 90 biopsies from 24 patients were studied. The registrations were validated by checking prostate contour alignment using image overlay, and the results were accurate to within 2 mm. The mean target displacement, needle placement error, and clinical biopsy error were 5.2, 2.5, and 4.3 mm, respectively. CONCLUSION: The biopsy error reported suggests that quantitative imaging techniques for prostate registration and motion compensation may improve prostate biopsy targeting accuracy.

Mitochondria-related gene expression changes are associated with fatigue in patients with nonmetastatic prostate cancer receiving external beam radiation therapy.

BACKGROUND: Cancer-related fatigue (CRF) is associated with negative health outcomes and decreased health-related quality of life; however, few longitudinal studies have investigated molecular-genetic mechanisms of CRF. OBJECTIVE: The objective of this study was to describe relationships between mitochondria-related gene expression changes and self-reported fatigue in prostate cancer patients receiving external beam radiation therapy (EBRT). METHODS: A prospective, exploratory, and repeated-measures design was used. Self-report questionnaires and peripheral whole-blood samples were collected from 15 patients at 7 time points. Baseline data were compared against 15 healthy controls. The Human Mitochondria RT Profiler PCR Array was used to identify differential regulation of genes involved in mitochondrial biogenesis and function. RESULTS: Compared with baseline, there were significant increases in fatigue scores (P = .02-.04) and changes in mitochondria-related gene expression (P = .001-.05) over time. Mean fatigue scores were 1.66 (SD, 1.66) at baseline, 3.06 (SD, 1.95) at EBRT midpoint, 2.98 (SD, 2.20) at EBRT completion, and 2.64 (SD, 2.56) at 30 days after EBRT. Over time, 11 genes related to mitochondrial function and structure were differentially expressed. Of these 11 genes, 3 (BCL2L1, FIS1, SLC25A37) were more than 2.5 fold up-regulated, and 8 (AIFM2, BCL2, IMMP2L, MIPEP, MSTO1, NEFL, SLC25A23, SLC25A4) were greater than 2-fold down-regulated. Furthermore, 8 genes (AIFM2, BCL2, FIS1, IMMP2L, MSTO1, SLC25A23, SLC25A37, SLC25A4) were significantly associated with the changes in fatigue scores. CONCLUSION: This study provides preliminary evidence that 8 mitochondrial function genes were significantly associated with fatigue in prostate cancer patients during EBRT. IMPLICATIONS FOR PRACTICE: These findings identify possible pathways and early biomarkers for targeting novel interventions for CRF.

Radiation therapy for the management of patients with HTLV-1-associated adult T-cell leukemia/lymphoma.

Human T-cell leukemia virus type 1-associated adult T-cell leukemia/lymphoma (ATL) typically has survivals measured in months with chemotherapy. One prior published series (1983-1991) assessed local radiotherapy for ATL. Ten consecutive patients with pathologically confirmed ATL treated with radiotherapy were reviewed. Subtypes included acute (n = 7), smoldering (n = 2), and lymphomatous (n = 1). Patients received an average of 2.5 systemic therapy regimens before radiotherapy. Twenty lesions (cutaneous = 10, nodal = 8, extranodal = 2) were treated to a mean of 35.4 Gy/2-3 Gy (range, 12-60 Gy). At 9.0-month mean follow-up (range, 0.1-42.0 months), all lesions symptomatically and radiographically responded, with in-field complete responses in 40.0% (nodal 37.5% vs. cutaneous 50.0%; P = .62). No patient experienced in-field progression. Nine patients developed new/progressive out-of-field disease. Median survival was 17.0 months (3-year survival, 30.0%). No Radiation Therapy Oncology Group acute grade ≥ 3 or any late toxicity was noted. This report is the first to use modern radiotherapy techniques and finds effective local control across ATL subtypes. Radiotherapy should be considered for symptomatic local progression of ATL.