Intrathecal pemetrexed for leptomeningeal metastases in a patient with ALK-rearranged lung adenocarcinoma: a case report.

Progressive leptomeningeal metastases (LM) are associated with intractable neurological symptoms and a poor prognosis, and effective treatment options are limited. Intrathecal (IT) pemetrexed has been shown to confer clinical benefit in lung adenocarcinoma, yet our understanding of the efficacy and safety of the treatment is limited. We report a patient with a long-standing history of leptomeningeal disease due to ALK-positive adenocarcinoma of the lung, previously controlled by increased doses of lorlatinib (125 mg/day).

c.1155-3A>G is a pathogenic variant that causes aberrant splicing, disrupted parafibromin expression, and hyperparathyroidism-jaw tumor syndrome.

Germline and somatic pathogenic variants in the gene, encoding the nuclear protein parafibromin, increase the risk for parathyroid carcinoma and cause hereditary primary hyperparathyroidism (PHPT) syndromes known as familial isolated hyperparathyroidism (FIHP) and hyperparathyroidism-jaw tumor syndrome (HPT-JT). The identification of pathogenic germline variants in PHPT-susceptibility genes can influence surgical planning for parathyroidectomy, guide screening for potential syndromic manifestations, and identify/exonerate at-risk family members. Numerous types of pathogenic germline variants have been described for -related conditions, including deletion, truncating, missense, and splice site mutations.

Systematic Review of the Comparative Studies of Image-guided Thermal Ablation, Stereotactic Radiosurgery, and Sublobar Resection for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

The Clinical Practice Standards Committee of the American Association for Thoracic Surgery assembled an expert panel and conducted a systematic review of the literature detailing studies directly comparing treatment options for high-risk patients with stage I non-small cell lung cancer (NSCLC). A systematic search was performed to identify publications comparing outcomes following image-guided thermal ablation (IGTA), stereotactic ablative radiotherapy (SABR), and sublobar resection-the main treatment options applicable to high-risk patients with stage I NSCLC. There were no publications detailing completed randomized controlled trials comparing these treatment options.

Systematic Review of Stereotactic Ablative Radiotherapy (SABR)/ Stereotactic Body Radiation Therapy (SBRT) for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

Stereotactic ablative radiotherapy (SABR) has emerged as an alternative, non-surgical treatment for high-risk patients with stage I non-small cell lung cancer (NSCLC) with increased use over time. The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) assembled an expert panel and conducted a systematic review of the literature evaluating the results of SABR, which is also referred to as stereotactic body radiation therapy (SBRT) or stereotactic radiosurgery (SRS), prior to developing treatment recommendations for high-risk patients with stage I NSCLC based on expert consensus. Publications detailing the findings of 16 prospective studies of SABR and 14 retrospective studies of SABR for the management of early-stage lung cancer in 54 697 patients were identified by systematic review of the literature with further review by members of our expert panel.

Systematic Review of Sublobar Resection for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

Sublobar resection offers a parenchymal-sparing surgical alternative to lobectomy and includes wedge resection and segmentectomy. Sublobar resection has been historically utilized in high-risk patients with compromised lung function; however, the technique is becoming more prevalent for normal-risk patients with peripheral lung tumors < 2 cm. In this article, we summarize the technique of sublobar resection, the importance of surgical margins and lymph node sampling, patient selection, perioperative complications, outcomes, and the impact of sublobar resection on the quality of life.

Menopausal hormone therapy: assessing associations with breast and colorectal cancers by familial risk.

Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.

Targeting peptide antigens using a multiallelic MHC I-binding system.

Identifying highly specific T cell receptors (TCRs) or antibodies against epitopic peptides presented by class I major histocompatibility complex (MHC I) proteins remains a bottleneck in the development of targeted therapeutics. Here, we introduce targeted recognition of antigen-MHC complex reporter for MHC I (TRACeR-I), a generalizable platform for targeting peptides on polymorphic HLA-A*, HLA-B* and HLA-C* allotypes while overcoming the cross-reactivity challenges of TCRs. Our TRACeR-MHC I co-crystal structure reveals a unique antigen recognition mechanism, with TRACeR forming extensive contacts across the entire peptide length to confer single-residue specificity at the accessible positions.

African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1.

Recently, an African ancestry-specific Parkinson disease (PD) risk signal was identified at the gene encoding glucocerebrosidase (GBA1). This variant ( rs3115534 -G) is carried by ~50% of West African PD cases and imparts a dose-dependent increase in risk for disease. The risk variant has varied frequencies across African ancestry groups but is almost absent in European and Asian ancestry populations.

Polygenic Risk Score and Upgrading in Patients With Prostate Cancer Receiving Active Surveillance.

Importance: Active surveillance is the preferred management strategy for patients with low- or favorable intermediate-risk prostate cancer (PCa); however, frequent health care visits can be costly and burdensome to patients. Identifying patients who may benefit from intensive vs passive surveillance could reduce these burdens.

Objective: To investigate associations between a polygenic risk score (PRS) and risk of upgrading and other prostate tumor features in patients receiving active surveillance.

Treatment Selection for the High-risk Patient with Stage I Non-Small Cell Lung Cancer: Sublobar Resection, Stereotactic Ablative Radiotherapy or Image-guided Thermal Ablation?

Objective: A significant proportion of patients with stage I non-small cell lung cancer (NSCLC) are considered at high risk for complications or mortality after lobectomy. The American Association for Thoracic Surgery (AATS) previously published an expert consensus document detailing important considerations in determining who is at high risk. The current objective was to evaluate treatment options and important factors to consider during treatment selection for these high-risk patients.

Systematic Review of Image-guided Thermal Ablation for Treatment of High-Risk Patients with Stage I Non-Small Cell Lung Cancer.

Image-guided thermal ablation (IGTA) applied to pulmonary pathology is an alternative to surgery in high-risk patients with stage I non-small cell lung cancer (NSCLC). Its application to lung neoplasm was first introduced in 2001 and has been implemented to treat metastatic disease to the lung or in select medically inoperable patients with peripheral stage I NSCLC. IGTA may also be an alternative to treat stage I NSCLC in non-operable patients with interstitial lung disease in whom a radiation modality is deemed too high risk.

The Importance of Pulmonary Nodule Features in the Selection of Treatment for the High-risk Patient with Stage I Non-Small Cell Lung Cancer.

Objective: The American Association for Thoracic Surgery (AATS) Clinical Practice Standards Committee (CPSC) previously published important considerations in determining who is at high risk for complications or mortality after lobectomy. Sublobar resection, stereotactic ablative radiotherapy, or image-guided thermal ablation is typically considered when the risks associated with lobectomy are high. The current objective was to evaluate important lung-nodule-related factors to consider during treatment selection for high-risk patients with stage I non-small cell lung cancer (NSCLC).

Case report: Dramatic impact of DNA next generation sequencing results using specific targeted therapies- and .

In the era of targeted therapies, the clinical importance and utility of next-generation sequencing (NGS) has expanded significantly. Owing to the relative ease and financial feasibility of NGS, the use of personalized treatment strategies has the potential to revolutionize cancer care. In this case report, we explored the use of NGS in salivary gland carcinoma (SGC) and spindle cell neoplasm of the scalp.

Presentation and Management of Highly Differentiated Follicular Carcinoma of Ovarian Origin With Gene Variants.

Struma ovarii (SO) is a rare subtype of ovarian teratoma composed of more than 50% thyroid tissue. Extraovarian spread of SO, called peritoneal strumosis, was previously considered benign given the lack of histological malignant features. However, the 2020 World Health Organization Classification of Female Genital Tumors reclassified peritoneal strumosis as highly differentiated follicular carcinoma of ovarian origin (HDFCO), highlighting its low-grade malignant potential.

Emotional Reactivity and Regulation Relate to Surgical Treatment Decision Making Among Newly Diagnosed Women With Breast Cancer.

Background: Despite bilateral mastectomy (BLM) for early-stage breast cancer (BC) showing no survival benefit and increased risk compared to breast conserving surgery, some patients still choose this treatment. This study examined whether emotion reactivity and regulation influence treatment decision making among newly diagnosed women with breast cancer.

Methods: Cross-sectional survey data were analyzed as part of a larger study.

Correlative studies reveal factors contributing to successful CAR-T cell therapies in cancer.

Cellular and targeted immunotherapies have revolutionized cancer treatments in the last several decades. Successful cellular therapies require both effective and durable cytotoxic activity from the immune cells as well as an accessible and susceptible response from targeted cancer cells. Correlative studies from clinical trials as well as real-world data from FDA-approved therapies have revealed invaluable insights about immune cell factors and cancer cell factors that impact rates of response and relapse to cellular therapies.

Cancers adapt to their mutational load by buffering protein misfolding stress.

In asexual populations that don't undergo recombination, such as cancer, deleterious mutations are expected to accrue readily due to genome-wide linkage between mutations. Despite this mutational load of often thousands of deleterious mutations, many tumors thrive. How tumors survive the damaging consequences of this mutational load is not well understood.

Unraveling the genetic landscape of susceptibility to multiple primary cancers.

With advances in cancer screening and treatment, there is a growing population of cancer survivors who may develop subsequent primary cancers. While hereditary cancer syndromes account for only a portion of multiple cancer cases, we sought to explore the role of common genetic variation in susceptibility to multiple primary tumors. We conducted a cross-ancestry genome-wide association study (GWAS) and transcriptome-wide association study (TWAS) of 10,983 individuals with multiple primary cancers, 84,475 individuals with single cancer, and 420,944 cancer-free controls from two large-scale studies.