Chapter 14: POST-SURGICAL FOLLOW-UP.

Primary hyperparathyroidism is treated surgically. Postoperatively, close monitoring of blood calcium levels is necessary to detect any hypocalcemia. Postoperative PTH assays can be performed within 24 hours to identify patients who will not develop permanent hypoparathyroidism.

Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors.

Understanding the genomic landscape of breast cancer brain metastases (BCBMs) is key to developing targeted treatments. In this study, targetable genomic profiling was performed on 822 BCBMs, 11,988 local breast cancer (BC) biopsies and 15,516 non-central nervous system (N-CNS) metastases (all unpaired samples) collected during the course of routine clinical care by Foundation Medicine Inc (Boston, MA). Clinically relevant genomic alterations were significantly enriched in BCBMs compared to local BCs and N-CNS metastases.

Clinical impact of UV mutational signatures in Veterans with cancer.

Background: UV-related DNA damage signature (UVsig) is highly specific for cutaneous cancers. The prevalence of UVsig among tumors without a primary site and tumors of extracutaneous origin were previously reported, suggesting potential misclassification of cancers. Our study aims to assess if the knowledge of UVsig at diagnosis would change first-line treatment recommendation.

Molecular heterogeneity in urothelial carcinoma and determinants of clinical benefit to PD-L1 blockade.

Checkpoint inhibitors targeting programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) have revolutionized cancer therapy across many indications including urothelial carcinoma (UC). Because many patients do not benefit, a better understanding of the molecular mechanisms underlying response and resistance is needed to improve outcomes. We profiled tumors from 2,803 UC patients from four late-stage randomized clinical trials evaluating the PD-L1 inhibitor atezolizumab by RNA sequencing (RNA-seq), a targeted DNA panel, immunohistochemistry, and digital pathology.

Therapeutic vulnerabilities and pan-cancer landscape of BRAF class III mutations in epithelial solid tumors.

Background: Kinase-impaired class III BRAF mutations have recently received attention as a possible prognostic factor and therapeutic target. Class III BRAF variants differ from class I and class II mutations in terms of mechanism of pathway activation and therapeutic vulnerabilities. Genomic landscape analyses of tumors in large real-world cohorts represent a great opportunity to further characterize tumor-related molecular events and treatment vulnerabilities, however, such data is not yet available for tumors with BRAF class III mutations.

Artificial intelligence-based morphologic classification and molecular characterization of neuroblastic tumors from digital histopathology.

A deep learning model using attention-based multiple instance learning (aMIL) and self-supervised learning (SSL) was developed to perform pathologic classification of neuroblastic tumors and assess MYCN-amplification status using H&E-stained whole slide images from the largest reported cohort to date. The model showed promising performance in identifying diagnostic category, grade, mitosis-karyorrhexis index (MKI), and MYCN-amplification with validation on an external test dataset, suggesting potential for AI-assisted neuroblastoma classification.

Molecular characteristics of advanced colorectal cancer and multi-hit PIK3CA mutations.

Introduction: Approximately 20% of patients living with colorectal cancer (CRC) have activating mutations in their tumors in the PIK3CA oncogene. Two or more activating mutations (multi-hit) for the PIK3CA allele increase PI3K⍺ signaling compared to single-point mutations, resulting in exceptional response to PI3K⍺ inhibition. We aimed to identify the prevalence of PIK3CA multi-hit mutations in metastatic CRC to identify patients who may benefit from PI3K inhibitors.

Single-Hit and Multi-hit PIK3CA Short Variant Genomic Alterations in Clinically Advanced Prostate Cancer: A Genomic Landscape Study.

Background: Tumors harboring two or more PIK3CA short variant (SV) ("multi-hit") mutations have been linked to improved outcomes with anti-PIK3CA-targeted therapies in breast cancer. The landscape and clinical implications of multi-hit PIK3CA alterations in clinically advanced prostate cancer (CAPC) remains elusive.

Objective: To evaluate the genomic landscape of single-hit and multi-hit PIK3CA genomic alterations in CAPC.

Use of UV mutational signatures to distinguish between cutaneous and pulmonary primary squamous cell carcinoma.

Background: Squamous cell carcinoma (SCC) of presumed lung origin (PLO) is now the second most frequent histologic subtype of non-small cell carcinoma after adenocarcinoma. The use of clinic-genomic correlation provided by comprehensive genomic profiling (CGP) can revise clinicopathologic diagnoses of presumed primary lung SCC (PLO-SCC) to diagnoses of metastatic SCC of cutaneous origin (C-SCC).

Design: A total of 10 146 samples of clinically advanced PLO-SCC (84% known Stage IV) passed QC metrics and were designated as PLO-SCCs by review of test requisition forms, clinical notes, and pathology reports.

Transvaginal Mesh Versus Native Tissue Repair for Anterior and Apical Pelvic Organ Prolapse.

Objectives: This prospective comparative cohort study aims to evaluate the safety and efficacy of transvaginal mesh compared to native tissue repair (NTR) in the surgical correction of anterior and apical compartment pelvic organ prolapse (POP) over a 36-month follow-up period.

Methods: Prospective comparative cohort study to prove superiority for efficacy and non-inferiority for serious adverse events (SAEs). The setting was 49 sites across the United States, Canada, Europe, and Australia.

Higher tumor mutational burden and PD-L1 expression correlate with shorter survival in hematologic malignancies.

Background: The prognostic implications of tumor mutational burden (TMB) and programmed death ligand 1 (PD-L1) expression are poorly studied in hematologic malignancies.

Objectives: This study aimed to better understand the characteristics and prognostic value of TMB and PD-1/PD-L1 in hematologic malignancies.

Design: This real-world study was conducted among patients with hematologic malignancies who had next-generation sequencing (NGS) (Foundation Medicine) at the University of California San Diego Moores Cancer Center (2014-2018).

Neuroblastoma, Version 2.2024, NCCN Clinical Practice Guidelines in Oncology.

Neuroblastoma is the most common extracranial solid tumor diagnosed in children. This inaugural version of the NCCN Guidelines for Neuroblastoma provides recommendations for the diagnosis, risk classification, and treatment of neuroblastoma. The information in these guidelines was developed by the NCCN Neuroblastoma Panel, a multidisciplinary group of representatives with expertise in neuroblastoma, consisting of pediatric oncologists, radiologists, pathologists, surgeons, and radiation oncologists from NCCN Member Institutions.

Effectiveness of PARP Inhibitor Maintenance Therapy in Ovarian Cancer by BRCA1/2 and a Scar-Based HRD Signature in Real-World Practice.

Purpose: The purpose of the study was to compare the effectiveness of PARP inhibitor maintenance therapy (mPARPi) in real-world practice by biomarker status [BRCA1/2 alterations (BRCAalt) and a homologous recombination deficiency signature (HRDsig)] in advanced ovarian cancer.

Experimental Design: Patients with ovarian cancer receiving first-line platinum-based chemotherapy and either mPARPi or no maintenance were included. Patient data were obtained by a US-based de-identified ovarian cancer Clinico-Genomic Database, from ∼280 US cancer clinics (01/2015-03/2023).

Genomic profiling and comparative analysis of male versus female metastatic breast cancer across subtypes.

Background: Male breast cancer (MaBC) has limited data on genomic alterations. We aimed to comprehensively describe and compare MaBC's genomics with female breast cancer's (FBC) across subtypes.

Methods: Using genomic data from Foundation Medicine, we categorized 253 MaBC into estrogen receptor (ER)-positive/human epidermal growth factor receptor 2 (HER2)-negative (n = 210), ER-positive/HER2-positive (n = 22) and triple-negative (n = 20).

Ancestry-associated co-alteration landscape of KRAS and EGFR-altered non-squamous NSCLC.

Racial/ethnic disparities mar NSCLC care and treatment outcomes. While socioeconomic factors and access to healthcare are important drivers of NSCLC disparities, a deeper understanding of genetic ancestry-associated genomic landscapes can better inform the biology and the treatment actionability for these tumors. We present a comprehensive ancestry-based prevalence and co-alteration landscape of genomic alterations and immunotherapy-associated biomarkers in patients with KRAS and EGFR-altered non-squamous (non-Sq) NSCLC.

Morphology and composition of calcium oxalate monohydrate phytoliths in the bark of Betula ermanii (stone birch): Case study from Sakhalin Island.

The morphology of calcium oxalate monohydrate precipitates (COM, Ca(CO)·HO, P2/c, whewellite) occurring as crystals or intergrowths, as well as distribution of crystal-bearing idioblasts, have been studied for the first time in the bark of stone birch Betula ermanii from Sakhalin Island sampled in an area affected by mud volcanism and an unaffected typical forest environment taken for reference. The study addresses several issues (i) number and size of phytoliths and their distribution in different cell types; (ii) density of calcification in specific cells; (iii) habits of single crystals, twins, and complex intergrowths, as well as frequency of different morphologies and their relations. The trends of time-dependent morphological changes in separately analyzed crystals and intergrowths record the evolution of COM morphology from nuclei to mature grains.

Artificial intelligence-based morphologic classification and molecular characterization of neuroblastic tumors from digital histopathology.

A deep learning model using attention-based multiple instance learning (aMIL) and self-supervised learning (SSL) was developed to perform pathologic classification of neuroblastic tumors and assess -amplification status using H&E-stained whole slide digital images. The model demonstrated strong performance in identifying diagnostic category, grade, mitosis-karyorrhexis index (MKI), and -amplification on an external test dataset. This AI-based approach establishes a valuable tool for automating diagnosis and precise classification of neuroblastoma tumors.

Analysis of Breast Cancer Brain Metastases Reveals an Enrichment of Cyclin-Dependent Kinase 12 Structural Rearrangements in Human Epidermal Growth Factor Receptor 2-Positive Disease.

Purpose: Genomic alterations have been identified in patients with breast cancer brain metastases (BCBMs), but large structural rearrangements have not been extensively studied.

Materials And Methods: We analyzed the genomic profiles of 822 BCBMs and compared them with 11,988 local, breast-biopsied breast cancers (BCs) and 15,516 non-CNS metastases (Non-CNS M) derived from formalin-fixed paraffin-embedded material using targeted capture sequencing.

Results: Nine genes with structural rearrangements were more prevalent within BCBMs as compared with local BCs and Non-CNS M (adjusted- < .