Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

The dysfunctional immune response in renal cell carcinoma correlates with changes in the metabolic landscape of ccRCC during disease progression.

Renal cell carcinoma is an immunogenic tumour with a prominent dysfunctional immune cell infiltrate, unable to control tumour growth. Although tyrosine kinase inhibitors and immunotherapy have improved the outlook for some patients, many individuals are non-responders or relapse despite treatment. The hostile metabolic environment in RCC affects the ability of T-cells to maintain their own metabolic programme constraining T-cell immunity in RCC.

Radiation-induced recto-urinary fistula: A dreaded complication with devastating consequences.

Purpose: This study was undertaken to evaluate our 16-year experience with fistulas between the rectum and urethra or urinary bladder, collectively called recto-urinary fistulas (RUFs), and their devastating consequences in patients treated with radiation for prostate cancer.

Methods: We downloaded the records of all patients with radiation-related RUFS from 2004 to 2020 at our institution using the electronic medical record system. Details concerning patient demographics, clinical presentation, diagnostic approaches and surgical management were obtained and assessed.

Determinants of anti-PD-1 response and resistance in clear cell renal cell carcinoma.

ADAPTeR is a prospective, phase II study of nivolumab (anti-PD-1) in 15 treatment-naive patients (115 multiregion tumor samples) with metastatic clear cell renal cell carcinoma (ccRCC) aiming to understand the mechanism underpinning therapeutic response. Genomic analyses show no correlation between tumor molecular features and response, whereas ccRCC-specific human endogenous retrovirus expression indirectly correlates with clinical response. T cell receptor (TCR) analysis reveals a significantly higher number of expanded TCR clones pre-treatment in responders suggesting pre-existing immunity.

The BARCODE1 Pilot: a feasibility study of using germline single nucleotide polymorphisms to target prostate cancer screening.

Objectives: To assess the feasibility and uptake of a community-based prostate cancer (PCa) screening programme selecting men according to their genetic risk of PCa. To assess the uptake of PCa screening investigations by men invited for screening. The uptake of the pilot study would guide the opening of the larger BARCODE1 study recruiting 5000 men.

Selection of metastasis competent subclones in the tumour interior.

The genetic evolutionary features of solid tumour growth are becoming increasingly well described, but the spatial and physical nature of subclonal growth remains unclear. Here, we utilize 102 macroscopic whole-tumour images from clear cell renal cell carcinoma patients, with matched genetic and phenotypic data from 756 biopsies. Utilizing a digital image processing pipeline, a renal pathologist marked the boundaries between tumour and normal tissue and extracted positions of boundary line and biopsy regions to X and Y coordinates.

Detection and staging of radio-recurrent prostate cancer using multiparametric MRI.

Objective: We determined the sensitivity and specificity of multiparametric magnetic resonance imaging (MP-MRI) in detection of locally recurrent prostate cancer and extra prostatic extension in the post-radical radiotherapy setting. Histopathological reference standard was whole-mount prostatectomy specimens. We also assessed for any added value of the dynamic contrast enhancement (DCE) sequence in detection and staging of local recurrence.

Longitudinal Trends of Financial Toxicity in Patients With Lung Cancer: A Prospective Cohort Study.

Background: Cancer therapy is associated with severe financial burden. However, the magnitude and longitudinal patient relationship with financial toxicity (FT) in the initial course of therapy is unclear.

Methods: Patients with stage II-IV lung cancer were recruited in a prospective longitudinal study between July 2018 and March 2020.

Porphyria cutanea tarda exacerbation as a paraneoplastic syndrome in vaginal cancer resolved with chemoradiation.

. The effects of therapeutic ionizing radiation in patients with PCT are not well understood. We report the case of a 55 year-old woman with a past medical history significant for kidney transplant with rejection and removal on hemodialysis, Stevens-Johnson syndrome, porphyria cutanea tarda, undifferentiated connective tissue disease probably systemic lupus, and hepatitis C, who underwent curative chemoradiation treatment for a recurrent vaginal squamous cell carcinoma.

Isolated progression of metastatic lung cancer: Clinical outcomes associated with definitive radiotherapy.

Background: Progressive, metastatic non-small cell lung cancer (NSCLC) often requires the initiation of new systemic therapy. However, in patients with NSCLC that is oligoprogressive (≤3 lesions), local radiotherapy (RT) may allow for the eradication of resistant microclones and, therefore, the continuation of otherwise effective systemic therapy.

Methods: Patients treated from 2008 to 2019 with definitive doses of RT to all sites of intracranial or extracranial oligoprogression without a change in systemic therapy were identified.

Consolidative Radiotherapy in Oligometastatic Lung Cancer: Patient Selection With a Prediction Nomogram.

Background: Patients with stage IV oligometastatic (≤ 3 sites) non-small-cell lung cancer have a progression-free survival (PFS) and overall survival benefit when all sites of metastatic disease and the primary tumor are treated radically with consolidative radiotherapy (cRT). However, the optimal selection of patients most likely from cRT is yet to be defined.

Patients And Methods: Patients with metastatic non-small-cell lung cancer treated with definitive radiotherapy to all metastatic sites and primary tumor (2008-2019) were retrospectively identified.

Prostate-specific membrane antigen expression in melanoma metastases.

Background: Prostate-specific membrane antigen (PSMA) is a prostatic epithelial protein that is used as a radiotracer (68Ga-PSMA-11) for prostate cancer staging. PSMA-PET/CT (positron emission tomography/computed tomography) performed for prostate cancer has been observed to detect melanoma metastases. The aim of this study was to investigate the performance of PSMA immunohistochemistry on resected melanoma metastases to explore its use as a diagnostic imaging biomarker for melanoma.

Representative Sequencing: Unbiased Sampling of Solid Tumor Tissue.

Although thousands of solid tumors have been sequenced to date, a fundamental under-sampling bias is inherent in current methodologies. This is caused by a tissue sample input of fixed dimensions (e.g.

Hospitalization and definitive radiotherapy in lung cancer: incidence, risk factors and survival impact.

Background: Unplanned hospitalization during cancer treatment is costly, can disrupt treatment, and affect patient quality of life. However, incidence and risks factors for hospitalization during lung cancer radiotherapy are not well characterized.

Methods: Patients treated with definitive intent radiation (≥45 Gy) for lung cancer between 2008 and 2018 at a tertiary academic institution were identified.

Exploring the Relationship of Radiation Dose Exposed to the Length of Esophagus and Weight Loss in Patients with Lung Cancer.

Purpose: We investigate whether esophageal dose-length parameters (L) can robustly predict significant weight loss-≥5% weight loss during radiation therapy (RT) compared with the weight before RT-in patients with lung cancer treated with definitive intent.

Methods And Materials: Patients with lung cancer treated with conventionally fractionated RT between 2010 and 2018 were retrospectively identified. L and L, the length of full- and partial-circumferential esophagus receiving greater than a threshold dose in Gy, respectively, were created.

Financial toxicity in lung cancer: an assessment of magnitude, perception, and impact on quality of life.

Background: Advances in lung cancer therapy have resulted in improved clinical outcomes. Unfortunately, advances can come at a financial cost to patients and their families that poses a significant risk to overall quality of life (QoL). Financial distress has been shown to be associated with increased symptom burden and decreased treatment compliance but the magnitude of financial distress is not well characterized in lung cancer populations.

Standard and Hypofractionated Dose Escalation to Intraprostatic Tumor Nodules in Localized Prostate Cancer: Efficacy and Toxicity in the DELINEATE Trial.

Purpose: To report a planned analysis of the efficacy and toxicity of dose escalation to the intraprostatic dominant nodule identified on multiparametric magnetic resonance imaging using standard and hypofractionated external beam radiation therapy.

Methods And Materials: DELINEATE is a single centre prospective phase 2 multicohort study including standard (cohort A: 74 Gy in 37 fractions) and moderately hypofractionated (cohort B: 60 Gy in 20 fractions) prostate image guided intensity modulated radiation therapy in patients with National Comprehensive Cancer Network intermediate- and high-risk disease. Patients received an integrated boost of 82 Gy (cohort A) and 67 Gy (cohort B) to lesions visible on multiparametric magnetic resonance imaging.

Image-Guided Gynecologic Brachytherapy for Cervical Cancer.

The incorporation of magnetic resonance imaging in brachytherapy has resulted in an increased use of interstitial catheters in order to create a comprehensive treatment plan that covers the visualized tumor. However, the insertion with passive, image-guidance requires estimating the location of the tumor during the insertion process, rather than visualizing and inserting the catheters directly to the desired location under active tracking. In order to treat residual disease, multiparametric MR sequences can enhance the information available to the clinician.

Updated risk models demonstrate low risk of symptomatic radionecrosis following stereotactic radiosurgery for brain metastases.

Background: Improvements in systemic therapy continue to increase survival for patients with brain metastases. Updated dosimetric models are required to optimize long-term safety of stereotactic radiosurgery (SRS) for this indication.

Methods: Patients at a single institution receiving SRS from December 2011 to December 2014 were retrospectively reviewed.

Validation of T2- and diffusion-weighted magnetic resonance imaging for mapping intra-prostatic tumour prior to focal boost dose-escalation using intensity-modulated radiotherapy (IMRT).

Background And Purpose: To assess the diagnostic accuracy and inter-observer agreement of T2-weighted (T2W) and diffusion-weighted (DW) magnetic resonance imaging (MRI) for mapping intra-prostatic tumour lesions (IPLs) for the purpose of focal dose-escalation in prostate cancer radiotherapy.

Materials And Methods: Twenty-six men selected for radical treatment with radiotherapy were recruited prospectively and underwent pre-treatment T2W+DW-MRI and 5 mm spaced transperineal template-guided mapping prostate biopsies (TTMPB). A 'traffic-light' system was used to score both data sets.