Treatment Response Biomarkers: Working Toward Personalized Radiotherapy for Lung Cancer.

Owing to major advances in the field of radiation oncology, patients with lung cancer can now receive technically individualized radiotherapy treatments. Nevertheless, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies. Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome.

Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model.

Genomic rearrangements of the neurotrophic receptor tyrosine kinase genes (NTRK1, NTRK2, and NTRK3) are the most common mechanism of oncogenic activation for this family of receptors, resulting in sustained cancer cell proliferation. Several targeted therapies have been approved for tumours harbouring NTRK fusions and a new generation of TRK inhibitors has already been developed due to acquired resistance. We established a patient-derived LMNA::NTRK1-rearranged soft-tissue sarcoma cell model ex vivo with an acquired resistance to targeted TRK inhibition.

Role of enzalutamide in primary and recurrent non-metastatic hormone sensitive prostate cancer: a systematic review of prospective clinical trials.

Introduction: Enzalutamide, a second-generation androgen receptor inhibitor, is indicated for the treatment of metastatic disease, as well as in the treatment of non-metastatic castration resistant prostate cancer (PCa). This systematic review aims to determine outcomes and toxicity in patients with non-metastatic castration sensitive prostate cancer (nmCSPC) treated with enzalutamide in the primary or salvage settings.

Method: We performed a systematic review focusing on the role of Enzalutamide in the treatment of nmCSPC, using the PubMed/Medline database.

Severity-Dependent Interhemispheric White Matter Connectivity Predicts Poststroke Neglect Recovery.

Left-sided spatial neglect is a very common and challenging issue after right-hemispheric stroke, which strongly and negatively affects daily living behavior and recovery of stroke survivors. The mechanisms underlying recovery of spatial neglect remain controversial, particularly regarding the involvement of the intact, contralesional hemisphere, with potential contributions ranging from maladaptive to compensatory. In the present prospective, observational study, we assessed neglect severity in 54 right-hemispheric stroke patients (32 male; 22 female) at admission to and discharge from inpatient neurorehabilitation.

MRI Extracellular Volume Fraction in Liver Fibrosis-A Comparison of Different Time Points and Blood Pool Measurements.

Background: Extracellular volume (ECV) correlates with the degree of liver fibrosis.

Purpose: To analyze the performance of liver MRI-based ECV evaluations with different blood pool measurements at different time points.

Study Type: Prospective.

Tumor Intrinsic Subtypes and Gene Expression Signatures in Early-Stage ERBB2/HER2-Positive Breast Cancer: A Pooled Analysis of CALGB 40601, NeoALTTO, and NSABP B-41 Trials.

Importance: Biologic features may affect pathologic complete response (pCR) and event-free survival (EFS) after neoadjuvant chemotherapy plus ERBB2/HER2 blockade in ERBB2/HER2-positive early breast cancer (EBC).

Objective: To define the quantitative association between pCR and EFS by intrinsic subtype and by other gene expression signatures in a pooled analysis of 3 phase 3 trials: CALGB 40601, NeoALTTO, and NSABP B-41.

Design, Setting, And Participants: In this retrospective pooled analysis, 1289 patients with EBC received chemotherapy plus either trastuzumab, lapatinib, or the combination, with a combined median follow-up of 5.

Head and neck reconstruction with the superficial circumflex iliac artery perforator (SCIP) free flap: Lessons learned after 73 cases.

Background: Head and neck tissue defects after ablative surgery often require complex and composite reconstructions. The superficial circumflex iliac artery perforator (SCIP) flap is an extremely versatile perforator-based flap with minimal donor site morbidity, which may represent the optimal procedure in this setting. Over the last 5 years, we collected a large base of experience, including both simple and chimeric SCIP-based reconstruction, making this flap our first choice for head and neck reconstructions.

Multicenter evaluation of an automated, multiplex, RNA-based molecular assay for detection of ALK, ROS1, RET fusions and MET exon 14 skipping in NSCLC.

The current study assessed the performance of the fully automated RT-PCR-based Idylla™ GeneFusion Assay, which simultaneously covers the advanced non-small cell lung carcinoma (aNSCLC) actionable ALK, ROS1, RET, and MET exon 14 rearrangements, in a routine clinical setting involving 12 European clinical centers. The Idylla™ GeneFusion Assay detects fusions using fusion-specific as well as expression imbalance detection, the latter enabling detection of uncommon fusions not covered by fusion-specific assays. In total, 326 archival aNSCLC formalin-fixed paraffin-embedded (FFPE) samples were included of which 44% were resected specimen, 46% tissue biopsies, and 9% cytological specimen.

The optimal number of induction chemotherapy cycles in clinically lymph node-positive bladder cancer.

Objective: To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node-positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection.

Patients And Methods: We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose-dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1-3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups.

Cervical and thoracic spinal cord gray matter atrophy is associated with disability in patients with amyotrophic lateral sclerosis.

Background And Purpose: In amyotrophic lateral sclerosis (ALS), there is an unmet need for more precise patient characterization through quantitative, ideally operator-independent, assessments of disease extent and severity. Radially sampled averaged magnetization inversion recovery acquisitions (rAMIRA) magnetic resonance imaging enables gray matter (GM) and white matter (WM) area quantitation in the cervical and thoracic spinal cord (SC) with optimized contrast. We aimed to investigate rAMIRA-derived SC GM and SC WM areas and their association with clinical phenotype and disability in ALS.

Safety and quality of cystectomy and pelvic lymph node dissection after neoadjuvant durvalumab and cisplatin/gemcitabine.

Objective: To report on the surgical safety and quality of pelvic lymph node dissection (PLND) in patients treated with radical cystectomy (RC) and PLND for muscle-invasive bladder cancer (MIBC) after neoadjuvant chemo-immunotherapy.

Patients And Methods: The Swiss Group for Clinical Cancer Research (SAKK) 06/17 was an open-label single-arm phase II trial including 61 cisplatin-fit patients with clinical stage (c)T2-T4a cN0-1 operable urothelial MIBC or upper urinary tract cancer. Patients received neoadjuvant cisplatin/gemcitabine and durvalumab followed by surgery.

Use of Indocyanine Green Near-Infrared Imaging for Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Pilot Study.

Purpose: The current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of technetium-labeled nanosized colloids (Tc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique.

5qSMA: standardised retrospective natural history assessment in 268 patients with four copies of SMN2.

Newborn screening for 5qSMA offers the potential for early, ideally pre-symptomatic, therapeutic intervention. However, limited data exist on the outcomes of individuals with 4 copies of SMN2, and there is no consensus within the SMA treatment community regarding early treatment initiation in this subgroup. To provide evidence-based insights into disease progression, we performed a retrospective analysis of 268 patients with 4 copies of SMN2 from the SMArtCARE registry in Germany, Austria and Switzerland.

Do PET-positive supradiaphragmatic lymph nodes predict overall survival or the success of primary surgery in patients with advanced ovarian cancer?

Objectives: Compared to conventional computed tomography (CT), fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) detects higher rates of lymph node and distant metastases in patients with ovarian cancer. However, FDG-PET/CT is not routinely performed during preoperative work-up. Therefore, we investigated the prognostic value of preoperative FDG-PET/CT in advanced epithelial ovarian cancer (EOC) and its predictive value for surgical resection in patients with no residual disease.

Radiotherapy statements of the 18th St. Gallen International Breast Cancer Consensus Conference-a German expert perspective.

Purpose: To summarize the radiotherapy-relevant statements of the 18th St. Gallen Breast Cancer Consensus Conference and interpret the findings in light of German guideline recommendations.

Methods: Statements and voting results from the 18th St.

Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence.

Background: Hepatic artery infusion chemotherapy (HAI) has been proposed as a valuable adjunct for multimodal therapy of primary and secondary liver malignancies. This review provides an overview of the currently available evidence of HAI, taking into account tumor response and long-term oncologic outcome.

Summary: In colorectal liver metastases (CRLM), HAI in combination with systemic therapy leads to high response rates (85-90%) and conversion to resectablity in primary unresectable disease in up to 50%.

Isolated melanoma cells in sentinel lymph node in stage IIIA melanoma correlate with a favorable prognosis similar to stage IB.

Background: The American Joint Committee on Cancer 8th edition (AJCC v8) defines sentinel lymph nodes (SLN) containing any tumor cells as positive SLN. Consequently, even thin melanomas with isolated tumor cells (ic) in SLN are classified as stage IIIA, making them candidates for adjuvant therapy.

Objectives And Endpoints: We aimed to evaluate survival outcomes of melanoma stage IIIA (ic) and compare them with stage IIIA with lymph node (LN) metastases > 0.

Unlocking the Potential of Adequate Bacillus Calmette-Guérin Immunotherapy in Very-high-risk Non-muscle-invasive Bladder Carcinoma: A Multicenter Analysis of Oncological Outcomes and Risk Dynamics.

Background: The European Association of Urology (EAU) recommends discussing upfront radical cystectomy for all patients with very high risk (VHR) non-muscle-invasive bladder carcinoma (NMIBC), but the role of bacillus Calmette-Guérin (BCG) treatment remains controversial.

Objective: To analyze oncological outcomes in VHR NMIBC patients (EAU risk groups) treated with adequate BCG.

Design, Setting, And Participants: A multi-institutional retrospective study involving patients with VHR NMIBC who received adequate BCG therapy from 2007 to 2020 was conducted.

Challenges and pitfalls during CRT implantation in patients with persistent left superior vena cava.

Background: Persistent left superior vena cava (PLSVC) is a rare venous anomaly, affecting 0.3-0.5% of the general population.

High concordance of molecular subtyping between pre-surgical biopsy and surgical resection specimen (matched-pair analysis) in patients with vulvar squamous cell carcinoma using p16- and p53-immunostaining.

Objective: Vulvar squamous cell carcinoma (VSCC) can be stratified into three molecular subtypes based on the immunoexpression of p16 and p53: HPV-independent p53-abnormal (p53abn) (most common, biologically aggressive), HPV-associated, with p16-overexpression (second most common, prognostically more favourable) and more recently recognised HPV-independent p53-wildtype (p53wt) (rarest subtype, prognostically intermediate). Our aim was to determine whether molecular subtypes can be reliably identified in pre-operative biopsies and whether these correspond to the subsequent vulvectomy specimen.

Methods: Matched-paired pre-surgical biopsies and subsequent resection specimen of 57 patients with VSCC were analysed for the immunohistochemical expression of p16 and p53 by performing a three-tiered molecular subtyping to test the accuracy rate.

Radiomics in Musculoskeletal Tumors.

Sarcomas are heterogeneous rare tumors predominantly affecting the musculoskeletal (MSK) system. Due to significant variations in their natural history and variable response to conventional treatments, the discovery of novel diagnostic and prognostic biomarkers to guide therapeutic decision-making is an active and ongoing field of research. As new cellular, molecular, and metabolic biomarkers continue to be discovered, quantitative radiologic imaging is becoming increasingly important in sarcoma management.

First-line durvalumab in patients with PD-L1 positive, advanced non-small cell lung cancer (NSCLC) with a performance status of 2 (PS2). Primary analysis of the multicenter, single-arm phase II trial SAKK 19/17.

Introduction: The safety and efficacy of first-line durvalumab in PS2 patients with advanced NSCLC is unknown. Here, we present the primary analysis of first-line durvalumab in PS2 patients, unsuitable for combination chemotherapy.

Methods: In this single-arm, multicenter, phase II trial patients with PD-L1 positive (tumor proportional score ≥25%), advanced NSCLC with PS2, received four-weekly durvalumab 1500 mg.