Acute and Chronic Complications After Treatment of Locoregional Anal Cancer: Prevention and Management Strategies.

Definitive chemoradiotherapy (CRT) for anal cancer spares patients the morbidity of a colostomy surgery and optimizes cancer outcomes. CRT, however, has introduced a unique acute and chronic toxicity profile, which has greatly improved over the years with the introduction of advanced radiotherapy techniques. This article provides the multidisciplinary care team with practical tools to mitigate and manage acute and chronic complications from definitive treatment of anal cancer.

Loss of histone H3K27me3 identifies a subset of meningiomas with increased risk of recurrence.

Epigenetic patterns on the level of DNA methylation have already been shown to separate clinically relevant subgroups of meningiomas. We here set out to identify potential prognostic implications of epigenetic modification on the level of histones with focus on H3K27 trimethylation (H3K27me3). H3K27me3 was assessed by immunohistochemistry on 232 meningiomas from 232 patients. In 194 cases, trimethylation was detected in tumor cells. In 25 cases, staining was limited to vessels while all tumor cells were negative. Finally, 13 cases yielded equivocal staining patterns. Reduced abundance of H3K27me3 in cases with staining limited to vessels was confirmed by mass spectrometry on a subset of cases. Lack of staining for H3K27me3 in all tumor cells was significantly associated with more rapid progression (p = 0.009). In line, H3K27me3-negative cases were associated with a DNA methylation pattern of the more aggressive types among the recently introduced DNA methylation groups. Also, NF2 and SUFU mutations were enriched among cases with complete lack of H3K27me3 staining in tumor cells (p < 0.0001 and p = 0.029, respectively). H3K27me3 staining pattern added significant prognostic insight into WHO grade II cases and in the compound subset of WHO grade I and II cases (p = 0.04 and p = 0.007, respectively). However, it did not further stratify within WHO grade III cases. Collectively, these data indicate that epigenetic modifications beyond DNA methylation are involved in the aggressiveness of meningioma. It also suggests that H3K27me3 immunohistochemistry might be a useful adjunct in meningioma diagnostics, particularly for cases with WHO grade II histology or at the borderline between WHO grade I and II.

Psychosocial Intervention for Family Caregivers of ALS Patients: A Systematic Review.

PROPOSAL: This systematic review aims to comprehensively examine all existing knowledge on psychosocial interventions for family caregivers for ALS patients. Also, the study will present the gaps in knowledge, recommendations for future research, and guidelines for psychosocial interventions that are focused and adapted to the needs of family caregivers of ALS patients. MATERIALS AND METHODS: The systematic review was conducted according to the PRISMA guidelines and identified studies on psychosocial intervention for family caregivers of ALS patients, using five electronic databases: PsychNET, PubMed, EBSCO, PRIMO, and PROQUEST. Seven articles met the criteria and were included in the review. A thematic analysis was conducted to extract major themes. RESULTS: Three major themes emerged from the data: (1) Personal benefits; (2) Interpersonal benefits; and (3) Charting challenges and pathways to improve psychosocial interventions. CONCLUSIONS: Based on the findings, practical guidelines were formulated that focus on the group's composition, the facilitator's role, the contents, the relationships within the group, and the opportunities and limitations of online interventions.

A whole-blood RNA transcript-based prognostic model in men with castration-resistant prostate cancer: a prospective study.

BACKGROUND: Survival for patients with castration-resistant prostate cancer is highly variable. We assessed the effectiveness of a whole-blood RNA transcript-based model as a prognostic biomarker in castration-resistant prostate cancer. METHODS: Peripheral blood was prospectively collected from 62 men with castration-resistant prostate cancer on various treatment regimens who were enrolled in a training set at the Dana-Farber Cancer Institute (Boston, MA, USA) from August, 2006, to June, 2008, and from 140 patients with castration-resistant prostate cancer in a validation set from Memorial Sloan-Kettering Cancer Center (New York, NY, USA) from August, 2006, to February, 2009. A panel of 168 inflammation-related and prostate cancer-related genes was assessed with optimised quantitative PCR to assess biomarkers predictive of survival. FINDINGS: A six-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1, CDKN1A) separated patients with castration-resistant prostate cancer into two risk groups: a low-risk group with a median survival of more than 34·9 months (median survival was not reached) and a high-risk group with a median survival of 7·8 months (95% CI 1·8-13·9; p<0·0001). The prognostic utility of the six-gene model was validated in an independent cohort. This model was associated with a significantly higher area under the curve compared with a clinicopathological model (0·90 [95% CI 0·78-0·96] vs 0·65 [0·52-0·78]; p=0·0067). INTERPRETATION: Transcriptional profiling of whole blood yields crucial prognostic information about men with castration-resistant prostate cancer. The six-gene model suggests possible dysregulation of the immune system, a finding that warrants further study. FUNDING: Source MDX.

Achieving the Unachievable: Work-Life Balance in Radiation Oncology.

As radiation oncologists, we often participate in discussions on work-life balance, are offered lectures and free meals, and complete hospital-mandated modules, all under the guise of physician wellness. But how often are these measures efficacious? How do we define being well in our demanding and fast-paced careers? What does it actually look like on a day-to-day basis to achieve work-life balance? Furthermore, is it even possible?

Robotic-assisted transaxillary parathyroidectomy of an atypical adenoma.

The advancement of minimally invasive surgical technologies over the past several years has led to improved surgical outcomes and greater patient satisfaction. Particularly for patients undergoing parathyroidectomies, endoscopic surgeries resulted in smaller surgical scars when compared with the open approach. Early endoscopic methods, however, were still restricted in their ability to provide adequate dexterity, two-dimensional views of the operative field; and while smaller than open surgeries, still left the presence of a small cervical scar. The limitations of endoscopic surgery led to application of the da Vinci S surgical robot system (Intuitive Surgical, Sunnyvale, CA, USA) and a novel transaxillary approach for parathyroidectomy. This surgical technique and approach is ideal for patients with primary hyperparathyroidism. This case report demonstrates that parathyroidectomy with en bloc thyroid lobectomy for atypical parathyroid adenomas using robotic- assisted transaxillary surgery is safe and feasible.

Stereotactic Body Radiation Therapy for the Treatment of Locally Recurrent and Oligoprogressive Non-Small Cell Lung Cancer: A Single Institution Experience.

Objectives: To investigate the efficacy and safety of lung stereotactic body radiation therapy (SBRT) for non-small cell lung cancer (NSCLC) including oligorecurrent and oligoprogressive disease. Methods: Single-institution retrospective analysis of 60 NSCLC patients with 62 discrete lesions treated with SBRT between 2008 and 2017. Patients were stratified into three groups, including early stage, locally recurrent, and oligoprogressive disease. Group 1 included early stage local disease with no prior local therapy. Group 2 included locally recurrent disease after local treatment of a primary lesion, and group 3 included regional or well-controlled distant metastatic disease receiving SBRT for a treatment naive lung lesion (oligoprogressive disease). Patient/tumor characteristics and adverse effects were recorded. Local failure free survival (LFFS), progression free survival (PFS), and overall survival (OS) were estimated using the Kaplan Meier method. Results: At median follow-up of 34 months, 67% of the study population remained alive. The estimated 3-year LFFS for group 1, group 2, and group 3 patients was 95% (95% CI: 86%-100%), 82%(62% - 100%), and 83% (58-100%), respectively. The estimated 3-year PFS was 59% (42-83%), 40% (21%-78%), and 33% (12%-95%), and the estimated 3-year OS was 58% (41-82%), 60% (37-96%), and 58% (31-100%)), respectively for each group. When adjusted for age and size of lesion, no significant difference in OS, LFFS, and PFS emerged between groups (p > 0.05). No patients experienced grade 3 to 5 toxicity. Eighteen patients (29%) experienced grade 1 to 2 toxicity. The most common toxicities reported were cough and fatigue. Conclusions: Our data demonstrates control rates in group 1 patients comparable to historical controls. Our study also reveals comparable clinical results for SBRT in the treatment of NSCLC by demonstrating similar rates of LFFS and OS in group 2 and group 3 patients with locally recurrent and treatment naïve lung lesion with well-controlled distant metastatic disease.

Targeted Intraoperative Radiotherapy (TARGIT-IORT) for Early-Stage Invasive Breast Cancer: A Single Institution Experience.

Purpose/Objective: We present our single-institution experience in the management of invasive breast cancer with targeted intraoperative radiotherapy (TARGIT-IORT), focusing on patient suitability for IORT determined by the American Society for Radiation Oncology (ASTRO) Accelerated Partial Breast Irradiation (APBI) consensus guidelines. Materials/Methods: We identified 237 patients treated for biopsy-proven early-stage invasive breast cancer using low energy x-ray TARGIT-IORT at the time of lumpectomy between September 2013 and April 2020 who were prospectively enrolled in an institutional review board (IRB) approved database. We retrospectively reviewed preoperative and postoperative clinicopathologic factors to determine each patient's ASTRO APBI suitability (suitable, cautionary or unsuitable) according to the 2017 consensus guidelines (CG). Change in suitability group was determined based on final pathology. Kaplan-Meier methods were used to estimate the survival probability and recurrence probability across time. Results: 237 patients were included in this analysis, based on preoperative clinicopathologic characteristics, 191 (80.6%) patients were suitable, 46 (19.4%) were cautionary and none were deemed unsuitable. Suitability classification changed in 95 (40%) patients based on final pathology from lumpectomy. Increasing preoperative lesion size or a body mass index (BMI) ≥ 30 kg/m2 were significant predictors for suitability group change. Forty-one (17.3%) patients received additional adjuvant whole breast radiotherapy after TARGIT-IORT. At a median follow up of 38.2 months (range 0.4 - 74.5), five (2.1%) patients had ipsilateral breast tumor recurrences (IBTR), including two (0.8%) true local recurrences defined as a recurrence in the same quadrant as the initial lumpectomy bed with the same histology as the initial tumor. IBTR occurred in 1/103 (0.09%) patient in the post-op suitable group, 4/98 (4.08%) patients in the post-op cautionary group, and no patients in the post-op unsuitable group. At 3-years, the overall survival rate was 98.4% and the local recurrence free survival rate was 97.1%. Conclusion: There is a low rate of IBTR after TARGIT-IORT when used in appropriately selected patients. Change in suitability classification pre to postoperatively is common, highlighting a need for further investigation to optimize preoperative patient risk stratification in this setting. Patients who become cautionary or unsuitable based on final pathology should be considered for additional adjuvant therapy.

Modern Management of High-risk Soft Tissue Sarcoma With Neoadjuvant Chemoradiation: A Single-center Experience.

OBJECTIVE: Neoadjuvant chemoradiation (NA-CRT), followed by resection of high-risk soft tissue sarcoma (STS), may offer good disease control and toxicity outcomes. We report on a single institution's modern NA-CRT experience. MATERIALS AND METHODS: Delay to surgical resection, resection margin status, extent of necrosis, tumor cell viability, presence of hyalinization, positron emission tomography (PET)/computed tomography data, and treatment toxicities were collected. Using the Kaplan-Meier survival analysis, 5-year overall survival, disease-free survival, distant metastasis-free survival, and local control (LC) were estimated. Clinicopathologic features and PET/computed tomography avidity changes were assessed for their potential predictive impact using the log-rank test. RESULTS: From 2011 to 2018, 37 consecutive cases of localized high-risk STS were identified. Twenty-nine patients underwent ifosfamide-based NA-CRT to a median dose of 50 Gy before en bloc resection. At a median follow-up of 40.3 months, estimated 5-year overall survival was 86.1%, disease-free survival 70.2%, distant metastasis-free survival 75.2%, and LC 86.7%. Following NA-CRT, a median reduction of 54.7% was observed in tumor PET avidity; once resected, median tumor necrosis of 60.0% with no viable tumor cells was detected in 13.8% of the cases. Posttreatment resection margins were negative in all patients, with 27.6% having a margin of ≤1 mm. Delays of over 6 weeks following the end of radiation treatment to surgical resection occurred in 20.7% cases and was suggestive of inferior LC (92.8% vs. 68.6%, P=0.025). CONCLUSIONS: This single-institution series of NA-CRT demonstrates favorable disease control. Delay in surgical resection was associated with inferior LC, a finding that deserves further evaluation in a larger cohort. LEVEL OF EVIDENCE: Level III-retrospective cohort study.

The Impact of Graduates' Job Preferences on the Current Radiation Oncology Job Market.

PURPOSE: To examine the role of radiation oncology (RO) graduates' application patterns and personal preferences in current labor concerns. METHODS AND MATERIALS: An anonymous, voluntary survey was distributed to 665 domestic RO graduates from 2013 to 2017. Questions assessed graduates' regional (Northeast [NE]; Midwest [MW]; South [SO]; West [WT]) job type and population size preferences. Top regional choice was compared across other categorical and numerical variables using the χ2 test and analysis of variance, respectively. RESULTS: Complete responses were obtained from 299 (45.0% response rate) participants: 82 (27.4%), 74 (24.7%), 85 (28.4%), and 58 (19.4%) graduated from NE, MW, SO, and WT programs. The most to least commonly applied regions were SO (69.2%), MW (55.9%), and then NE/WT (55.2% each). The first and last regional choices were the WT (29.4%) and MW (15.7%), respectively. The most and least common application and top choice preferences were consistent in terms of city size: >500,000 (86.0% and 64.5%, respectively) and <100,001 (26.1% and 7.0%, respectively). The majority of applicants applied to both academic and nonacademic positions (60.9%), with top job type choice being equally split. The majority of respondents independently received a job offer in their preferred region (75.3%), city population size (72.6%) or job type (81.9%). Additionally, 52.5% received a job offer that included all three preferences. Those who underwent residency training (44.3% vs 62.0%-83.6%, P < .001) or medical schooling (50.7% vs 56.3%-75.6%, P < .001) or grew up in the MW (60.8% vs 70.0%-74.7%, P < .001) were least likely to choose this region as their top regional choice compared with other regions. CONCLUSIONS: The MW and jobs in smaller cities are less appealing to RO graduates, even if they receive training in the MW, which may contribute to current job market concerns. Nonetheless, the majority of respondents received a job offer in the region, population size, and job type of their top choice. Assessing prospective candidates' city size and geographic preferences and prioritizing applicants who are compatible with positions may help address potential job market discrepancies.

3D treatment planning on helical tomotherapy delivery system.

The helical tomotherapy is a technologically advanced radiation dose delivery system designed to perform intensity-modulated radiation therapy (IMRT). It is mechanistically unique, based on a small 6-MV linear accelerator mounted on a ring gantry that rotates around the patient while the patient moves through a bore, ultimately yielding a helical path of radiation dose delivery. The helical pattern of dose delivery differentiated tomotherapy from other contemporary radiation therapy systems at the time of its inception. The accompanying 3-dimensional (3D) treatment planning system has been developed to solely support this specific type of dose delivery system. The treatment planning system has 2 modules identified as TomoHelical and TomoDirect to perform IMRT and conformal radiation therapy, respectively. The focus of this work within the scope of this special issue on 3D treatment planning systems is to assess the use of planning tools to generate treatment plans for helical tomotherapy. Clinical examples are used throughout to demonstrate the quality and differences of various clinical scenarios planned with tomotherapy.

Squamous cell carcinoma of the rectum: a consequence of immunosuppression resulting from inhibiting tumour necrosis factor (TNF)?

Treatment with tumour necrosis factor (TNF) antagonists may lead to enhanced susceptibility to certain malignancies. In particular, an association is seen emerging between TNF antagonists and development of squamous cell carcinomas (SCCs) of the skin (in association with psoriasis), the oral cavity, and in the anogenital areas (possibly related to prior human papilloma virus infection). We present here a case of a 53-year old woman with a history of severe rheumatoid arthritis (RA), most recently treated with the TNF antagonist etanercept plus methotrexate, presented to our service after several months of increasing left pelvis and buttock pain. Evaluation with a computerised tomography (CT)-directed biopsy of a pelvic side wall mass revealed a metastatic SCC. On a fluorodeoxyglucose (FDG) positron-emission tomography (PET) an additional area of uptake was identified in the left posterior rectum corresponding to a 1 cm nodule palpable on digital exam. Colonoscopic biopsy revealed a basaloid SCC of the rectum as the likely primary site. Immunosuppression following TNF antagonist therapy may have given arise to this unrestrained neoplastic growth. It thereby underscores the need for an initial baseline study of risk factors and identification of patients who are at higher risk for development of a malignancy, in order to achieve a diagnosis at an early stage.

Improving outcomes with recent advances in chemotherapy for castrate-resistant prostate cancer.

The FDA's approval of docetaxel in 2004 created a clear mandate for clinical researchers to create new therapies effective for metastatic castrate-resistant prostate cancer (mCRPC) patients with progression post-docetaxel. In 2010, the first trial to prolong survival in this setting was announced using a cabazitaxel, a novel taxane. This therapeutic agent was specifically designed to have activity in model systems resistant to conventional taxanes. After phase I testing, with observation of clinically significant activity in patients with advanced cancers, cabazitaxel/prednisone was tested in a large phase III trial enrolling patients with mCRPC who had disease progression despite prior docetaxel therapy. This phase III trial TROPIC (Treatment of Hormone-Refractory Metastatic Prostate Cancer Previously Treated With a Taxotere-Containing Regimen), using mitoxantrone/prednisone as a control arm, demonstrated a significant improvement in survival (the primary endpoint). Both subset analyses and secondary endpoints (response rates and time to progression) were supportive of the survival findings. This trial was pivotal for the FDA's approval of the new drug application for cabazitaxel. This review focuses on both the pre-clinical and clinical development of cabazitaxel.