The Correlation Between Lymphocyte Nadir and Radiation Therapy for Soft Tissue Sarcoma: Defining Key Dosimetric Parameters and Outlining Clinical Significance.

Purpose: The objectives of this study were to identify key dosimetric parameters associated with postradiation therapy lymphopenia and uncover any effect on clinical outcomes. Methods and Materials: This was a retrospective review of 69 patients (between April 2010 and January 2023) who underwent radiation therapy (RT) as a part of curative intent for soft tissue sarcoma (STS) at a single academic institution. All patients with treatment plans available to review and measurable absolute lymphocyte count (ALC) nadir within a year after completion of RT were included. Results: Median follow-up was 22 months after the start of RT. A decrease in lymphocyte count was noted as early as during treatment and persisted at least 3 months after the completion of RT. On multivariable linear regression, the strongest correlations with ALC nadir were mean body dose, body V10 Gy, mean bone dose, bone V10 Gy, and bone V20 Gy. Five-year overall survival was 60% and 5-year disease-free survival was 44%. Advanced T-stage, chemotherapy use, use of intensity-modulated RT, lower ALC nadir, and the development of grade ≥2 lymphopenia at nadir were associated with worse overall survival and disease-free survival. Conclusions: Post-RT lymphopenia was associated with worse outcomes in STS. There were associations between higher body V10 Gy and bone V10 Gy and lower post-RT ALC nadir, despite the varying sites of STS presentation, which aligns with the well-known radiosensitivity of lymphocyte cell lines. These findings support efforts to reduce treatment-related hematopoietic toxicity as a way to improve oncologic outcomes. Additionally, this study supports the idea that the effect of radiation on lymphocyte progenitors in the bone marrow is more significant than that on circulating lymphocytes in treatments with limited involvement of the heart and lung.

Severity of Financial Toxicity for Patients Receiving Palliative Radiation Therapy.

Introduction: Financial toxicity has negative implications for patient well-being and health outcomes. There is a gap in understanding financial toxicity for patients undergoing palliative radiotherapy (RT). Methods: A review of patients treated with palliative RT was conducted from January 2021 to December 2022. The FACIT-COST (COST) was measured (higher scores implying better financial well-being). Financial toxicity was graded according to previously suggested cutoffs: Grade 0 (score ≥26), Grade 1 (14-25), Grade 2 (1-13), and Grade 3 (0). FACIT-TS-G was used for treatment satisfaction, and EORTC QLQ-C30 was assessed for global health status and functional scales. Results: 53 patients were identified. Median COST was 25 (range 0-44), 49% had Grade 0 financial toxicity, 32% Grade 1, 15% Grade 2, and 4% Grade 3. Overall, cancer caused financial hardship among 45%. Higher COST was weakly associated with higher global health status/Quality of Life (QoL), physical functioning, role functioning, and cognitive functioning; moderately associated with higher social functioning; and strongly associated with improved emotional functioning. Higher income or Medicare or private coverage (rather than Medicaid) was associated with less financial toxicity, whereas an underrepresented minority background or a non-English language preference was associated with greater financial toxicity. A multivariate model found that higher area income (HR .80, P = .007) and higher cognitive functioning (HR .96, P = .01) were significantly associated with financial toxicity. Conclusions: Financial toxicity was seen in approximately half of patients receiving palliative RT. The highest risk groups were those with lower income and lower cognitive functioning. This study supports the measurement of financial toxicity by clinicians.

Primary sarcoma of the liver: A nationwide analysis of a rare mesenchymal tumor.

BACKGROUND AND OBJECTIVES: Primary liver sarcomas are rare malignancies. Prognostic factors associated with long-term survival remain poorly understood. The objective of this study is to determine factors associated with long-term survival. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried to identify patients with visceral sarcoma arising from the liver. Demographic factors, tumor characteristics, resection status, and survival were evaluated. Multivariate Cox regression analysis was performed to determine predictors of survival. RESULTS: A total of 743 patients with primary hepatic sarcoma were identified. The median tumor size was 10 cm. Only 30% (n = 221) of patients in the cohort underwent surgery. The 5-year overall survival rates were 47.9% for localized disease, 29.5% for regional disease, and 16.5% for distant disease, p < 0.001. Among patients who underwent surgical resection, patients with embryonal sarcoma had better 5-year survival compared with angiosarcoma and other histologic subtypes. On multivariate analysis, surgery was associated with improved survival, while older age, higher stage, and angiosarcoma histology were the strongest independent predictors of poor survival. CONCLUSIONS: Surgery remains the mainstay of treatment for this rare malignancy but is performed in less than one-third of patients. Angiosarcoma histology is associated with worse overall survival, while surgical resection remains the strongest predictor of improved overall survival.

Goserelin-Induced Chemical Burn: A Case Report and Review of the Literature.

A chemical burn resulting from luteinizing hormone-releasing hormone agonists (LHRHa) is a rare adverse effect that has not been well-documented in prior literature. In this case report, we report a partial-thickness burn that developed following a single subcutaneous injection of goserelin. To our knowledge, this is the first description of goserelin-induced chemical burn in the literature. The importance of early identification and treatment of LHRHa-associated cutaneous reactions must be highlighted to ensure optimal oncologic management and patient comfort.

Single-molecule genome-wide mutation profiles of cell-free DNA for non-invasive detection of cancer.

Somatic mutations are a hallmark of tumorigenesis and may be useful for non-invasive diagnosis of cancer. We analyzed whole-genome sequencing data from 2,511 individuals in the Pan-Cancer Analysis of Whole Genomes (PCAWG) study as well as 489 individuals from four prospective cohorts and found distinct regional mutation type-specific frequencies in tissue and cell-free DNA from patients with cancer that were associated with replication timing and other chromatin features. A machine-learning model using genome-wide mutational profiles combined with other features and followed by CT imaging detected >90% of patients with lung cancer, including those with stage I and II disease. The fixed model was validated in an independent cohort, detected patients with cancer earlier than standard approaches and could be used to monitor response to therapy. This approach lays the groundwork for non-invasive cancer detection using genome-wide mutation features that may facilitate cancer screening and monitoring.

Endometrial Adenocarcinoma with Discordant Microsatellite Stability Status Treated with First-Line Pembrolizumab: A Case Report and Narrative Review.

BACKGROUND Microsatellite instability (MSI) is a hallmark of specific cancers and can be diagnosed using both tissue- and liquid-based approaches. When these tissue- and liquid-based approaches give differing results, they are known as discordant or being at variance. MSI-H tumors are well-researched candidates for treatment with programmed cell death protein 1 (PD-1) inhibitor-based immunotherapy, but the efficacy of immunotherapy in MSI-H discordant endometrial cancer, especially as first-line therapy, is not yet well documented in the literature. CASE REPORT A 67-year-old woman presented with a retroperitoneal mass positive for recurrent adenocarcinoma of endometrial origin. Her stage I endometrial adenocarcinoma 7 years ago demonstrated microsatellite stable (MSS) by immunohistochemical (IHC) stain and indeterminant due to insufficient tissue by Caris Next-Generation Sequencing (NGS). She then presented with a retroperitoneal mass that was MSI-H on IHC stain and Caris NGS, as well as MSI high on liquid biopsy @Guardant360 (@G360). The patient proceeded with pembrolizumab treatment 1 year ago and has sustained a complete clinical response at the time of writing. CONCLUSIONS Our case provides further evidence for the need to retest the microsatellite stability of metastatic sites, especially after a long disease-free survival. Here, we providing a literature review of case reports and a review of studies outlining discordance of testing modalities. Our case also highlights the importance of considering the use of immunotherapy as a first-line agent in patients who may have a poor ECOG performance status, as it can significantly improve their quality of life and reduce the number of adverse effects compared to chemotherapy.

Metastatic Colorectal Cancer Treatment Response Evaluation by Ultra-Deep Sequencing of Cell-Free DNA and Matched White Blood Cells.

PURPOSE: Circulating tumor DNA (ctDNA) has the potential to guide therapy selection and monitor treatment response in patients with metastatic cancer. However, germline and clonal hematopoiesis-associated alterations can confound identification of tumor-specific mutations in cell-free DNA (cfDNA), often requiring additional sequencing of tumor tissue. The current study assessed whether ctDNA-based treatment response monitoring could be performed in a tumor tissue-independent manner by combining ultra-deep targeted sequencing analyses of cfDNA with patient-matched white blood cell (WBC)-derived DNA. EXPERIMENTAL DESIGN: In total, 183 cfDNA and 49 WBC samples, along with 28 tissue samples, from 52 patients with metastatic colorectal cancer participating in the prospective phase III CAIRO5 clinical trial were analyzed using an ultra-deep targeted sequencing liquid biopsy assay. RESULTS: The combined cfDNA and WBC analysis prevented false-positives due to germline or hematopoietic variants in 40% of patients. Patient-matched tumor tissue sequencing did not provide additional information. Longitudinal analyses of ctDNA were more predictive of overall survival than standard-of-care radiological response evaluation. ctDNA mutations related to primary or acquired resistance to panitumumab were identified in 42% of patients. CONCLUSIONS: Accurate calling of ctDNA mutations for treatment response monitoring is feasible in a tumor tissue-independent manner by combined cfDNA and patient-matched WBC genomic DNA analysis. This tissue biopsy-independent approach simplifies sample logistics and facilitates the application of liquid biopsy ctDNA testing for evaluation of emerging therapy resistance, opening new avenues for early adaptation of treatment regimens.