Neoadjuvant chemotherapy for radiation associated angiosarcoma (RAAS) of the breast: A retrospective single center study.

Background: Radiation associated angiosarcoma (RAAS) of the breast is a rare malignancy with poor survival. Optimal treatment strategies remain uncertain due to a lack of data, and vary between surgery alone and a combination of surgery with (neo)adjuvant chemotherapy (NACT) and/or re-irradiation. The aim of this study was to evaluate the potential benefit of taxane based NACT.

The utility of DNA methylation profiling in the diagnosis of un-, de- and trans-differentiated melanoma: a series of 11 cases.

Aims: Melanomas are recognised for their remarkable morphological plasticity. Some tumours may lose conventional features and/or acquire non-melanocytic characteristics, referred to as undifferentiated, dedifferentiated and transdifferentiated melanoma. Despite this phenotypical variability, melanomas typically maintain their cancer driver aberrations, affecting genes such as BRAF, NRAS and NF1.

Propranolol monotherapy in angiosarcoma - A window-of-opportunity study (PropAngio).

Background: Angiosarcoma is a rare and aggressive cancer of the endothelial cells. Propranolol, a non-selective β-blocker, was able to initiate apoptosis in angiosarcoma cell lines and its anti-tumor activity has been described in several case reports. The aim of this trial was to prospectively evaluate the anti-tumor activity of propranolol monotherapy in patients with angiosarcoma before proceeding to standard of care treatment.

Correlation of radiological and histopathological response after neoadjuvant radiotherapy in soft tissue sarcoma.

Background: The aim of this study was to assess the association between radiological and histopathological response after neoadjuvant radiotherapy (nRT) in soft tissue sarcoma (STS), as well as the prognostic value of the different response evaluation methods on the oncological outcome.

Methods: A retrospective cohort of patients with localized STS of the extremity and trunk wall, treated with nRT followed by resection were included. The radiological response was assessed by RECIST 1.

Clinical Impact of Prospective Whole Genome Sequencing in Sarcoma Patients.

With more than 70 different histological sarcoma subtypes, accurate classification can be challenging. Although characteristic genetic events can largely facilitate pathological assessment, large-scale molecular profiling generally is not part of regular diagnostic workflows for sarcoma patients. We hypothesized that whole genome sequencing (WGS) optimizes clinical care of sarcoma patients by detection of diagnostic and actionable genomic characteristics, and of underlying hereditary conditions.

Artificial intelligence for diagnosis and Gleason grading of prostate cancer: the PANDA challenge.

Artificial intelligence (AI) has shown promise for diagnosing prostate cancer in biopsies. However, results have been limited to individual studies, lacking validation in multinational settings. Competitions have been shown to be accelerators for medical imaging innovations, but their impact is hindered by lack of reproducibility and independent validation.

Two Patients with Urachal Cancer with Multifocal Adenocarcinoma Recurrences in the Urothelium of the Prostatic and Penile Urethra.

We report two cases with recurrences of urachal adenocarcinoma (UrAC) in the urethra. Both patients had mucinous UrAC without metastasis, for which they were treated with en-bloc partial cystectomy and umbilectomy. The first patient developed recurrence of UrAC in the distal urethra after 1 yr.

Location of Gastrointestinal Stromal Tumor (GIST) in the Stomach Predicts Tumor Mutation Profile and Drug Sensitivity.

Purpose: Gastrointestinal stromal tumors (GIST) commonly arise in different regions of the stomach and are driven by various mutations (most often in KIT, PDGFRA, and SDHx). We hypothesized that the anatomic location of gastric GIST is associated with unique genomic profiles and distinct driver mutations.

Experimental Design: We compared KIT versus non-KIT status with tumor location within the National Cancer Database (NCDB) for 2,418 patients with primary gastric GIST.

Long-Term Risk of Ovarian Cancer and Borderline Tumors After Assisted Reproductive Technology.

Background: Long-term effects of assisted reproductive technology (ART) on ovarian tumor risk are unknown.

Methods: This nationwide cohort study comprises 30 625 women who received ovarian stimulation for ART in 1983-2000 and 9988 subfertile women not treated with ART. Incident invasive and borderline ovarian tumors were ascertained through linkage with the Netherlands Cancer Registry and the Dutch Pathology Registry until July 2018.

Local control and postponement of systemic therapy after modest dose radiotherapy in oligometastatic myxoid liposarcomas.

Introduction: Oligometastatic disease and/or oligoprogression in myxoid liposarcoma(oMLS) triggers discussions on local treatment options and delay of systemic treatments. We hypothesized that satisfactory local control and postponement of systemic therapy could be achieved with a modest radiotherapy(RT) dose in oMLS.

Methods: The DOREMY trial is a multicenter, phase 2 trial evaluating efficacy and toxicity of a modest RT dose in both localized and oMLS; this report presents the data of the oMLS cohort treated with 36 Gy in 12-18 fractions with optional subsequent metastasectomy.

Dose Reduction of Preoperative Radiotherapy in Myxoid Liposarcoma: A Nonrandomized Controlled Trial.

Importance: Currently, preoperative radiotherapy for all soft-tissue sarcomas is identical at a 50-Gy dose level, which can be associated with morbidity, particularly wound complications. The observed clinical radiosensitivity of the myxoid liposarcoma subtype might offer the possibility to reduce morbidity.

Objective: To assess whether a dose reduction of preoperative radiotherapy for myxoid liposarcoma would result in comparable oncological outcome with less morbidity.

Artificial intelligence assistance significantly improves Gleason grading of prostate biopsies by pathologists.

The Gleason score is the most important prognostic marker for prostate cancer patients, but it suffers from significant observer variability. Artificial intelligence (AI) systems based on deep learning can achieve pathologist-level performance at Gleason grading. However, the performance of such systems can degrade in the presence of artifacts, foreign tissue, or other anomalies.

Gastrointestinal Stromal Tumours (GIST) in Young Adult (18-40 Years) Patients: A Report from the Dutch GIST Registry.

Gastrointestinal stromal tumour (GIST) is a disease of older adults and is dominated by / mutations. In children, GIST is rare, predominantly occurs in girls, has a stomach location and generally lacks / mutations. For young adults (YA), aged 18 to 40 years, the typical phenotypic and genotypic patterns are unknown.

Automated deep-learning system for Gleason grading of prostate cancer using biopsies: a diagnostic study.

Background: The Gleason score is the strongest correlating predictor of recurrence for prostate cancer, but has substantial inter-observer variability, limiting its usefulness for individual patients. Specialised urological pathologists have greater concordance; however, such expertise is not widely available. Prostate cancer diagnostics could thus benefit from robust, reproducible Gleason grading.

Time dependent dynamics of wound complications after preoperative radiotherapy in Extremity Soft Tissue Sarcomas.

Aims: The purpose of the study was to investigate the time dependent dynamics of wound complications and local control after preoperative radiotherapy (RT) in Extremity Soft Tissue Sarcomas (ESTS).

Patients & Methods: In this retrospective cohort study, all patients treated for an extremity sarcoma with pre-operative radiotherapy followed by surgery were identified from a prospectively maintained database. A wound complication (WC) was defined as any local complication of the surgical area requiring intervention, hospital readmission or significant extension of the initial admission period.

Increased infiltration of M2-macrophages, T-cells and PD-L1 expression in high grade leiomyosarcomas supports immunotherapeutic strategies.

Immunotherapy may be a rational strategy in leiomyosarcoma (LMS), a tumor known for its genomic complexity. As a prerequisite for therapeutic applications, we characterized the immune microenvironment in LMS, as well as its prognostic value. CD163 macrophages, CD3 T-cells, PD-L1/PD-L2 and HLA class I expression (HCA2, HC10 and β2m) were evaluated using immunohistochemistry in primary tumors (n = 75), local relapses (n = 6) and metastases (n = 19) of 87 LMS patients, as well as in benign leiomyomas (n = 7).

Clinical characteristics and treatment outcome in a large multicentre observational cohort of PDGFRA exon 18 mutated gastrointestinal stromal tumour patients.

Purpose: Patients, platelet-derived growth factor receptor alpha (PDGFRA) D842V-mutated gastrointestinal stromal tumours (GISTs) are known for their insensitivity to imatinib. However, in clinical practice responses have been observed in some patients. We describe the natural history and treatment outcomes in a cohort of PDGFRA exon 18 mutated GIST patients.

Estrogen receptor α wields treatment-specific enhancers between morphologically similar endometrial tumors.

The DNA-binding sites of estrogen receptor α (ERα) show great plasticity under the control of hormones and endocrine therapy. Tamoxifen is a widely applied therapy in breast cancer that affects ERα interactions with coregulators and shifts the DNA-binding signature of ERα upon prolonged exposure in breast cancer. Although tamoxifen inhibits the progression of breast cancer, it increases the risk of endometrial cancer in postmenopausal women.

Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERα in Tamoxifen-Associated Endometrial Carcinomas.

Tamoxifen, a small-molecule antagonist of the transcription factor estrogen receptor alpha (ERα) used to treat breast cancer, increases risks of endometrial cancer. However, no parallels of ERα transcriptional action in breast and endometrial tumors have been found that might explain this effect. In this study, we addressed this issue with a genome-wide assessment of ERα-chromatin interactions in surgical specimens obtained from patients with tamoxifen-associated endometrial cancer.

Sunitinib pretreatment improves tumor-infiltrating lymphocyte expansion by reduction in intratumoral content of myeloid-derived suppressor cells in human renal cell carcinoma.

Targeted therapy with sunitinib, pazopanib or everolimus has improved treatment outcome for patients with metastatic renal cell carcinoma patients (RCC). However, despite considerable efforts in sequential or combined modalities, durable remissions are rare. Immunotherapy like cytokine therapy with interleukin-2, T cell checkpoint blockade or adoptive T cell therapies can achieve long-term benefit and even cure.

A phase I study on the combination of neoadjuvant radiotherapy plus pazopanib in patients with locally advanced soft tissue sarcoma of the extremities.

Unlabelled: Accumulating evidence suggests significant synergism combining radiotherapy (RT) with angiogenesis targeted therapies. This multicenter prospective phase I clinical trial established the safety profile and recommended dose for further studies of pazopanib concurrent with preoperative RT in patients with extremity soft tissue sarcomas (ESTS) in curative setting.

Methods: Patients with deep seated intermediate and high grade sarcomas, ≥ 5 cm, received once daily pazopanib (dose-escalation cohorts 400 mg, 600 mg and 800 mg) for 6 weeks and 50 Gy preoperative RT starting Day 8.

Detection of melanoma metastases in resected human lymph nodes by noninvasive multispectral photoacoustic imaging.

Objective. Sentinel node biopsy in patients with cutaneous melanoma improves staging, provides prognostic information, and leads to an increased survival in node-positive patients. However, frozen section analysis of the sentinel node is not reliable and definitive histopathology evaluation requires days, preventing intraoperative decision-making and immediate therapy.

Ultrasound examination and fine needle aspiration cytology-useful for followup of the regional nodes in penile cancer?

Purpose: Routine followup of the groins of patients with penile squamous cell carcinoma after primary treatment consists of physical examination together with ultrasound of the groins, followed by fine needle aspiration cytology if suspicious. We assessed the value of this routine followup.

Materials And Methods: Using ultrasound and fine needle aspiration cytology we assessed 247 patients during followup who were treated from 2004 to 2010 and underwent dynamic sentinel node biopsy only or observation of the inguinal regions.