Adjuvant Research Articles

Single-cell and bulk transcriptomic datasets enable the development of prognostic models based on dynamic changes in the tumor immune microenvironment in patients with hepatocellular carcinoma and portal vein tumor thrombus.

Hepatocellular carcinoma (HCC) patients exhibiting portal vein tumor thrombosis (PVTT) face a high risk of rapid malignant progression and poor outcomes, with this issue being compounded by a lack of effective treatment options. The integration of bulk RNA-sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) datasets focused on samples from HCC patients with PVTT has the potential to yield unprecedented insight into the dynamic changes in the tumor microenvironment (TME) and associated immunological characteristics in these patients, providing an invaluable tool for the reliable prediction of disease progression and treatment responses. scRNA-seq data from both primary tumor (PT) and PVTT cells were downloaded from the Gene Expression Omnibus (GEO) database, while the International Cancer Genome Consortium (ICGC) and Cancer Genome Atlas (TCGA) databases were used to access bulk RNA-seq datasets. scRNA-seq, clustering, GSVA enrichment, mutational profiling, and predictive immunotherapeutic treatment analyses were conducted using these data with the goal of systematically assessing the heterogeneity of PT and PVTT cells and establishing a model capable of predicting immunotherapeutic and prognostic outcomes in patients with HCC. These analyses revealed that PVTT cells exhibited patterns of tumor proliferation, stromal activation, and low levels of immune cell infiltration, presenting with immune desert and immune rejection-like phenotypes. PT cells, in contrast, were found to exhibit a pattern of immunoinflammatory activity. Core PVTT-associated genes were clustered into three patterns consistent with the tumor immune rejection and immune desert phenotypes. An established clustering model was capable of predicting tumor inflammatory stage, subtype, TME stromal activity, and patient outcomes. PVTT signature genes were further used to establish a risk model, with the risk scores derived from this model providing a tool to evaluate patient clinicopathological features including clinical stage, tumor differentiation, histological subtype, microsatellite instability status, and tumor mutational burden. These risk scores were also able to serve as an independent predictor of patient survival outcomes, responses to adjuvant chemotherapy, and responses to immunotherapy. In vitro experiments were used to partially validate the biological prediction results. These results offer new insight into the biological and immunological landscape of PVTT in HCC patients, By utilizing individual patient risk scores, providing an opportunity to guide more effective immunotherapeutic interventional efforts.

Preoperative chemo-CIRT in Re/BRe pancreatic cancer: Insights from a multicenter prospective phase II clinical study (NCT03822936).

There is debate about the optimal management of borderline resectable (bRe) and resectable (Re) pancreatic ductal adenocarcinoma (PDAC). Both preclinical and clinical evidence showed that carbon ion radiotherapy (CIRT) produces superior control on radioresistant histologies compared to conventional photon beam radiotherapy (RT). However, so far there is a lack of data concerning the integration of CIRT in a multimodal approach with chemotherapy and surgery for bRe/Re. We recently presented the first analysis of a multicenter prospective phase II clinical study aimed at assessing the feasibility and effectiveness of a neoadjuvant chemotherapy + short course of CIRT followed by surgery and adjuvant chemotherapy in the management of bRe/Re PDAC. The study was terminated early due to low patient enrollment.Herein, we reported a post-hoc analysis focusing on toxicity, dosimetry and translational assessment. In our experience, CIRT can be integrated into a multimodal treatment strategy for bRe/Re PDAC, alongside chemotherapy and surgery. A case of fatal liver failure occurring three months post-surgery has been documented, likely related to the combination approach. Although the treatment plans were satisfactory according to the Local Effect Model (LEM) model, recalculations using the modified Microdosimetric Kinetic Model (mMKM) revealed suboptimal target coverage. Additionally, we observed an increased expression of PD-L1 following CIRT. This multimodal approach was well tolerated; however, clinicians should carefully monitor for vascular disorders during follow-up and further investigate surgical techniques after CIRT. The increased PD-L1 expression supports the immunogenic effects of particle therapy and lays the groundwork for future studies. To enhance the therapeutic ratio of CIRT treatments, integrating dose-averaged LETd (LETd-based objectives into the plan optimization process should be considered. ClinicalTrials.gov Identifier: NCT03822936.

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

Adjuvant chemotherapy for isolated resectable colorectal lung metastasis: A retrospective study using inverse probability treatment weighting propensity analysis

Anticancer Potential of Tocopherols-Containing Plants and Semi-Synthetic Tocopherols.

Tocopherols, potent bioactive compounds with anticancer properties, remain understudied in herbal medicinal plants, presenting a significant knowledge gap in the field of natural anticancer agents. This review evaluates tocopherol-containing plants for their anticancer potential, analyzing Scopus publications from 2016 to 2024. Fifteen herbal medicinal plants were identified as promising candidates, including Bulbine anguistifolia Poelln, Punica granatum L., Moringa oleifera, Kigelia pinnata, and Typhonium flagelliforme Lodd. The review explores tocopherols' anticancer mechanisms, including apoptosis induction and cell cycle arrest. Factors influencing tocopherols' anticancer effects are examined, such as their forms (α, β, γ, δ), concentrations, plant parts utilized, and their stability in various plants. Additionally, emerging research on semi-synthetic tocopherol derivatives is analyzed, highlighting their potential as adjuvants in chemotherapy and their role in enhancing drug delivery and reducing side effects. This comprehensive analysis aims to advance the development of plant-based anticancer pharmaceuticals and improve cancer treatment strategies. By elucidating the mechanisms and potential of tocopherol-containing plants, this review provides a foundation for future research in plant-based anticancer therapies. It emphasizes the need for further investigation into these plants' anticancer properties, potentially leading to novel, more effective, and less toxic cancer therapies. The findings presented here contribute to a nuanced understanding of how tocopherol-containing plants can be leveraged in the development of future anticancer drugs.

Sex differences in recovery from postoperative sarcopenia during adjuvant CAPOX therapy for colorectal cancer

BackgroundWomen are predisposed to develop intolerance to cancer chemotherapy. Sarcopenia and chemotherapy are mutually related. Women are generally intolerable to chemotherapeutics such as 5-fluorouracil. Although adjuvant oxaliplatin-based chemotherapy, e.g. CAPOX is commonly used to treat colorectal cancer, its effects on patients in terms of sarcopenia and sex remain unknown. We investigated sex disparities in the impacts of CAPOX on body composition in this study.MethodsWe conducted a prospective study on diagnostic metrics used for sarcopenia in colorectal cancer patients receiving adjuvant CAPOX. Evaluations of the nutritional status by the Mini-Nutritional Assessment (MNA), gait speed, grip strength, skeletal muscle mass, fat mass, and bone mineral content using a body composition analyzer were performed in the first, fourth, and eighth cycles of CAPOX (first, second, and third measurements, respectively).ResultsAmong 80 eligible patients, 61 completed four CAPOX cycles. The median differences in MNA, gait, grip strength, muscle mass, fat mass, and bone mineral content between the first and second measurements for men (n = 35) and women (n = 26) were + 10.5% and + 2.9% (p = 0.067), + 4.5% and − 2.6% (p = 0.16), + 1.8% and + 2.8% (p = 0.66), + 2.7% and + 1.3% (p = 0.021), + 4.5% and + 3.5% (p = 0.59), and + 3.3% and + 0.0% (p = 0.006), There were no sex differences in comparisons of the above metrics between the first and third measurements in 34 patients who completed eight CAPOX cycles (19 wen and 15 women).ConclusionsEarly cycles of adjuvant CAPOX may have a negative impact on the postoperative recovery of several metrics for diagnosing sarcopenia in women.

Prognostic significance of adjuvant therapy and specific radiation dosages in Taiwanese patients with oral cavity cancer and extra-nodal extension: a nationwide cohort study

BackgroundThe evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE.MethodsA retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted.ResultsMultivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 − 7000 cGy, n = 1155 versus 6000 − 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578).ConclusionsFor OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600–7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients.

Immune checkpoint inhibitor therapy for primary neuroendocrine carcinoma of the gallbladder: A case report and literature review.

Gallbladder neuroendocrine carcinoma (GNEC) is indeed a relatively rare malignant tumor of the gallbladder with neuroendocrine differentiation and the ability to produce and secrete a number of neurotransmitters and hormones, characteristics that make its clinical presentation and biological behavior likely to be different from those of other types of gallbladder cancer. Current treatment mostly relies on surgery and adjuvant chemotherapy and radiotherapy. We report a 53-year-old middle-aged male patient who underwent radical surgery for gallbladder malignancy after a diagnosis of neuroendocrine carcinoma of the gallbladder. Diagnosis of neuroendocrine carcinoma of the gallbladder based on the return of pathologic findings. After local progression of postoperative chemotherapy with the first-line regimen of etoposide + cisplatin, an immune checkpoint inhibitor (traplizumab) + FOLIFIRI (fluorouracil + calcium folinate + irinotecan) regimen was used. The patient achieved 20 months of clinical survival and ultimately died of myelosuppression. The use of immune checkpoint inhibitors may become an effective tool in the treatment of neuroendocrine carcinoma of the gallbladder.

SS18-SSX Expression and Clinicopathologic Profiles in a Contemporary Cohort of Primary Paratesticular Synovial Sarcoma: A Series of Fourteen Patients.

Synovial sarcoma (SS) is a rare genitourinary malignancy with a specific SS18::SSX 1/2 gene fusion in majority of the instances. The paratesticular location of this neoplasm is extremely rare and only 4 cases are reported in the literature. Herein, we describe the clinicopathologic features and molecular profile of paratesticular SS in the largest case series to date and to the best of our knowledge, and the only series to use novel SS18-SSX antibody for immunohistochemistry. Clinicopathologic, immunohistochemical (IHC), molecular, treatment, and follow-up data of the patients were analyzed. There were 14 patients, ranging from 15 to 47 years (mean: 30y). The tumor size ranged from 4​​​​​​ to 15cm. The tumors were unilateral, solid, and homogeneous tan-white with monomorphic spindle cell histology. All 14 tumors expressed SS18-SSX and TLE1 IHC and harbored SS18 rearrangement. In addition, the tumor with multifocal SS18-SSX expression had lower break-apart signals in the FISH assay (38% of the tumor cells; range: 29% to 85%). Radical orchiectomy was performed in all 14 patients and adjuvant chemotherapy was administered in 9 patients. Follow-up was available in 9 patients. The follow-up duration ranged from 5 to 24 months (median=10mo). Four patients died of metastatic disease (range: 5 to 16mo) and 2 patients who are alive had metastatic disease at the last follow-up. Based on our experience with the largest series to date and aggregate of the published data, paratesticular SS has a poor prognosis despite aggressive therapy. Owing to its rarity, the differential diagnosis is wide and requires a systematic approach for ruling out key morphologic mimics aided with SS18-SSX IHC and molecular confirmation because this distinction carries important therapeutic and prognostic implications. Due to the excellent concordance of SS18-SSX IHC results with FISH results as observed in our study, we would like to suggest inclusion of SS18-SSX in the diagnostic immunohistochemistry panel of all spindle cell sarcomas where synovial sarcoma is considered as a morphologic differential. SS18-SSX-positive staining may be used as a surrogate for FISH assay in a resource-limited setting where molecular assay is not available. Furthermore, IHC has a fairly shorter turn-around-time, is less complex, and of low cost.

Fat necrosis after accelerated partial breast irradiation or hypofractionated whole breast irradiation: A case-control study.

This study aimed to compare the incidence of fat necrosis after accelerated partial breast irradiation (APBI) vs hypofractionated whole breast irradiation (WBI) in patients with early-stage breast cancer. Data from early-stage breast cancer patients who underwent breast-conserving surgery and adjuvant radiotherapy between 2009 and 2022 were retrospectively collected. Radiation therapy consisted of APBI of 30 Gy in 5 daily fractions (Fx) (delivered in one week, consecutively) to the tumour bed or WBI (42.4 Gy in 16 Fx). Reports on fat necrosis were extracted from yearly mammograms and breast ultrasound imaging. The primary endpoint was the incidence of radiologically detected fat necrosis. A total of 536 patients were included among the APBI and WBI cohorts, with 268 and 268 patients respectively. The three-year Kaplan-Meier actuarial rate of fat necrosis was 32.8% (95% CI: 30.0% - 35.6%) for APBI and 22.3% (95% CI: 19.7% - 24.9%) for WBI patients. Univariate Kaplan-Meier survival analysis revealed a Hazard Ratio of 1.6 [95% CI: 1.1 - 2.2; p = 0.0055] for the fat necrosis rate within the APBI group compared to WBI. Multivariate Cox proportional hazard regression confirmed significant associations between fat necrosis and APBI (HR = 2.2 95% CI: 1.2 - 4.0; p = 0.01). The occurrence of radiologically diagnosed fat necrosis was higher in the APBI group compared to the WBI. Further investigations aiming to identify a lower-dose schedule with comparable efficacy to 30 Gy in 5 Fx but fewer toxicities, particularly for high-risk patients, are warranted.

GSOR12 Presentation Time: 5:55 PM: Improved Survival with Adjuvant Radiation in Uterine Carcinosarcoma: A Retrospective Review

GSOR12 Presentation Time: 5:55 PM: Improved Survival with Adjuvant Radiation in Uterine Carcinosarcoma: A Retrospective Review

Guidelines for the Prophylaxis and Treatment of Peritoneal Metastases From Colorectal Cancer: A GRADE-Approach for Evidence Evaluation and Recommendations.

Colorectal peritoneal metastases (CPM) are common in colorectal cancer patients. This article aims to provide GRADE guidelines for the use of hyperthermic intraperitoneal chemotherapy (HIPEC) in two clinical situations: (1) To determine the value of adjuvant HIPEC for the prevention of CPM in high-risk colorectal cancer patients; (2) to determine the impact on survival of cytoreductive surgery and HIPEC followed by adjuvant systemic chemotherapy as compared to systemic chemotherapy alone in patients with CPM.

Clinical and Molecular Characteristics and Outcome of Adult Medulloblastoma at a Tertiary Cancer Center.

Background/Objectives: Adult medulloblastoma is a rare entity, with management data extrapolated from pediatric medulloblastoma cases. We aim to report the clinical characteristics, prognostic factors, and treatment outcome of a cohort of adult patients with medulloblastoma. Methods: Fifty-three patients aged ≥ 18 years with medulloblastoma treated at King Hussein Cancer Center between 2007 and 2019 were retrospectively reviewed. Patients' diseases were staged according to modified Chang's staging system. All patients received adjuvant craniospinal irradiation followed by a posterior fossa boost. Baseline disease characteristics, including molecular subgrouping, were tested as prognostic factors of progression-free survival (PFS) and overall survival (OS) by using univariate analysis. Results: Median follow-up was 70 months (range 37.5-104.5 months). Twenty-two tumors were of the SHH-activated subtype. Conversely, WNT-activated and group 4 tumors had three cases each. Only 37.7% of patients died. The mean 3-year, 5-year, and 10-year OS were 85% (75-95%), 74% (62-87%), and 50% (33-75%), respectively. Significant differences in OS were associated with the extent of surgery (p = 0.017), M stage (p = 0.009), and risk status (p < 0.001). Relapses were detected in 28.3% of cases. The 3-year, 5-year, and 10-year PFS were 81% (71-92%), 75% (63-88%), and 66% (52-83%), respectively. Significant differences in PFS were associated with the extent of surgery (p = 0.008) and risk status (p = 0.012). Molecular subgrouping did not correlate with OS or PFS. Conclusions: Our results revealed poor survival of patients with high-risk disease, which may necessitate the intensification of chemotherapy. Molecular subgrouping did not correlate with the outcome in this cohort.

The value of a multimodal approach combining radical surgery and intraoperative radiotherapy in the recurrence treatment of gynecological malignancies - analysis of a large patient cohort in a tertiary care center

BackgroundRecurrent and locally advanced gynecological malignancies have a poor prognosis. In particularly, pelvic local recurrence after previous radiotherapy and/or positive resection margins during surgical treatment for recurrent disease result in low survival rates. Consequently, locoregional control is of utmost importance in this cohort of patients. The aim of this study was to analyze treatment outcomes and determine prognostic factors for patients treated with surgery and intraoperative radiotherapy (IORT) for recurrent and locally advanced gynecological malignancies.Methods40 patients who underwent surgical treatment and IORT between 2010 and 2022 were eligible for inclusion. The median follow-up time was 22 months. The outcomes measured were locoregional control (LRC), overall survival (OS), and survival without distant metastases (DMFS). The Cox proportional hazards model was used for univariate and multivariate analysis to assess the impact of patient variables and treatment factors on the endpoints mentioned. The following variables were analyzed: age at surgical treatment and IORT and initial diagnosis (< 65 vs. ≥65 years, each), disease-free interval (DFI) between initial diagnosis and first recurrence, DFI to surgical treatment and IORT, grading, histology, IORT dose (≤ 13 vs. >13 Gy) and technique (high dose radiotherapy (HDR) vs. IORT using electrons, (IOERT)). Survival curves were generated using the Kaplan-Meier method.ResultsThe mean IORT dose was 13.8 Gy (range 10–18 Gy). Cervical carcinoma was most frequently found in 27.5% of patients followed by endometrial carcinoma and vulvar carcinoma in 25% respectively. The final histopathologic results after surgery with IORT showed no residual tumour in 24 patients (60%), microscopic residual disease in 5 patients (12.5%), resection status could not be evaluated in three patients (7.5%) and the resection status was unknown in eight patients (20%). Subsequently, 27.5% of patients also received adjuvant radiotherapy of the local recurrence bed. However, after IORT, 65% of the women suffered a recurrence. Of these, the recurrences were localized: in-field 32.5%, out-of-field 22.5% and margin-of-field 12.5%. The 3- and 5-year OS was 69% and 55% respectively. The 3- and 5-year LRC was 56% respectively. The 3- and 5-year DMFS was 66% and 49%. Whereas the comparison between groups by IORT dose level (≤ 13 vs. >13 Gy) showed a non-significant trend in favor of the higher dose only for OS (p = 0.094), but not in LRC and DMFS (p > 0.05). OS and DMFS, but not LRC, differed significantly between the HDR-IORT and IOERT groups (p = 0.06 and p = 0.03,) in favor of the HDR-IORT technique. For HDR-IORT technique a trend towards superior OS and LRC was observed in the univariate analysis: HR 3.76, CI 95%: 0.95–14.881, p = 0.059 and HR 2.165 CI 95%: 0.916–5.114, p = 0.078ConclusionsThe survival rate for pelvic recurrence in gynecological malignancies remains poor and comparable with historical data from the last two decades. Particularly HDR-IORT, appears to provide a long-term oncological benefit in carefully selected patients.

Zinc Influences the Efficacy of Betulinic Acid Treatment and Radiotherapy in Breast Cancer Cells

The trace element zinc influences a number of biological reactions, including cell growth, apoptosis, and DNA damage, which affect tumor therapy. The natural compound betulinic acid (BA) and its derivatives are known for their antiviral, antibacterial, and antitumor effects. Previous studies show that BA and 3-acetyl-28-sulfamoyloxybetulin (CAI3) have high cytotoxicity and induce radiosensitization in breast cancer cells. This study investigates the effects of zinc supplementation on treatment with BA or CAI3 and radiotherapy of breast cancer cell lines MDA-MB-231 and HS578T. Expression analysis shows that BA and CAI3 lead to altered expression of genes involved in zinc metabolism. Zinc supplementation affects cell survival and cell death alone and in combination with BA or CAI3 in both breast cancer cell lines. In MDA-MB-231 cells, zinc excess protects against ROS formation by BA or CAI3 and exhibits radioprotective effects compared to the single agent treatment. In contrast, in HS578T cells, zinc induces ROS formation but does not affect radiosensitivity. The variable effects of zinc on radiosensitivity highlight the importance of individualized treatment approaches. Although zinc has cytotoxic, pro-apoptotic, and anti-clonogenic effects, it seems worthwhile to consider its radioprotective properties when making treatment decisions in the case of adjuvant radiotherapy of breast cancer.

Downstaging Effect Rather than the Full Intended Cycles of Perioperative Chemotherapy Determines the Value of Adjuvant Chemotherapy in Gastric Cancer.

Perioperative chemotherapy is the standard treatment modality for locally advanced gastric cancer. However, the efficacy and indication of adjuvant chemotherapy in patients who have already received neoadjuvant chemotherapy remain unclear. This study aims to explore the association between adjuvant chemotherapy with patient prognosis in those who have received neoadjuvant chemotherapy plus D2 gastrectomy in a real-world setting, and whether this association is affected by the duration of neoadjuvant treatment. A total of 174 patients with cT3-4N+ gastric cancer who had received neoadjuvant chemotherapy plus D2 radical gastrectomy were included in the study. Kaplan-Meier curves and log-rank tests were used to assess and compare the survival outcomes between patients who received adjuvant therapy and those who did not. Patients who were younger age, had a lower American Society of Anesthesiologists (ASA) grade, did not experience postoperative complication, and received fewer than six cycles of neoadjuvant chemotherapy were more likely to receive adjuvant chemotherapy, rather than those with advanced ypTNM stage or poor tumor regression grade. Patients who received adjuvant therapy had a better overall survival (OS) (2-year OS rate 86.2% versus 64.1%, p=0.002). Adjuvant therapy was associated with longer survival in patients who remained ypTNM stage III despite receiving at least six cycles of neoadjuvant chemotherapy. However, there was no significant longer survival observed in patients with ypTNM stages 0-II receiving adjuvant chemotherapy, even when they received less than six cycles of neoadjuvant chemotherapy. Patients with locally advanced gastric cancer may still need adjuvant chemotherapy, even after receiving neoadjuvant chemotherapy. The value of adjuvant chemotherapy after neoadjuvant chemotherapy depends more on the actual downstaging effect achieved after neoadjuvant chemotherapy, rather than the completion of "full intended" cycles of perioperative treatment.

Molecular Alterations in Paired Epithelial Ovarian Tumors in Patients Treated with Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is a therapeutic choice for women with advanced ovarian cancer. Whether NACT affects the tumor's molecular profile has not been determined. This was a retrospective study of patients with advanced-stage epithelial ovarian cancer treated with NACT at oncology departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Tumor molecular profiling was performed on formalin-fixed and paraffin-embedded (FFPE) tumor pre- and post-NACT tissues. Homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), tumor molecular alterations, and tumor mutational burden (TMB) via next-generation sequencing analysis were assessed. Overall, tumors from 36 patients were assessed, and molecular profiling was evaluated in 20 paired tumor samples. HRD positivity exhibited no significant change between pre- and post-NACT tumors. The BRCA1/2 mutational status remained constant, irrespective of the treatment administration. Pre-NACT tumors tended to exhibit a lower percentage of intratumoral TILs compared to post-NACT tumors (p = 0.004). Differences in the mutation profile between pre- and post-treatment tissue were observed in 33.33% (6/18) of the cases. The mean tumor cell content (TCC) (p-value: 0.0840) and the mean genomic instability score (p-value: 0.0636) decreased slightly numerically after therapy. A moderate inverse relationship was observed between the pre-NACT TMB and the chemotherapy response score (p-value: 0.038), indicating this correlation is statistically significant. This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.

Perioperative systemic therapy, current paradigm and ongoing clinical trials in upper tract urothelial cancer.

To provide of comprehensive overview of existing and future paradigms for perioperative systemic therapy in the treatment of upper tract urothelial carcinoma. Contemporary treatment paradigms for the management of upper tract urothelial carcinoma focus on use of neoadjuvant cisplatin based chemotherapy for high grade disease primarily based on two small single arm phase II clinical trials. More robust evidence from a phase III randomized clinical trial exists for the use of adjuvant platinum based chemotherapy for invasive disease after radical nephroureterectomy, but there are significant concerns about renal function and platinum eligibility after nephroureterectomy. There are currently ongoing clinical trials for nonplatinum based perioperative systemic therapies including checkpoint inhibitors/immunotherapy as well as antibody-drug conjugates, but currently no recommendation can be made for these approaches. Current evidence supports neoadjuvant cisplatin chemotherapy in the setting of high grade disease or concern for significant renal dysfunction after radical nephroureterectomy or platinum based adjuvant chemotherapy in eligible patients with advanced disease after surgery. While there is no established role for nonplatinum based therapies yet, multiple ongoing trials exploring use of immunotherapies and antibody-drug conjugates as monotherapy or combination may provide new therapeutic options in this population.

NRXN1 as a Prognostic Biomarker: Linking Copy Number Variation to EMT and Survival in Colon Cancer.

The role of biomarkers in cancer treatment varies significantly depending on the cancer stage. Thus, in clinical practice, tailoring biomarkers to meet the specific needs and challenges of each cancer stage can increase the precision of treatment. Because they reflect underlying genetic alterations that influence cancer progression, copy number variation (CNV) biomarkers can play crucial prognostic roles. In our previous study, we identified potential survival-related genes for colorectal cancer (CRC) by analyzing CNV and gene expression data using a machine-learning approach. To further investigate the biological function of NRXN1, we assessed the use of RNA sequencing, phosphokinase assays, real-time quantitative PCR, and Western blot analysis. We found that NRXN1 copy number deletion was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS), even in patients who received adjuvant chemotherapy. Compared with its expression in normal tissues, NRXN1 expression was lower in tumors, suggesting its potential role as a tumor suppressor. NRXN1 knockdown enhanced CRC cell viability and invasion, and transcriptome analysis indicated that the increased invasion was caused by GSK3β-mediated epithelial-mesenchymal transition. These findings highlight NRXN1 copy number deletion as a novel biomarker for predicting recurrence and survival in patients with resected colon cancer.

Definitive-dose adjuvant radiotherapy following endoscopic submucosal dissection for superficial esophageal cancer.

Prophylactic chemoradiation therapy (CRT) using 40-41.4Gy post-endoscopic submucosal dissection (ESD) for clinical T1N0M0 esophageal cancer reportedly yields favorable outcomes. However, it cannot completely prevent locoregional lymph node (LN) metastases. We retrospectively analyzed outcomes and adverse events associated with our dose-escalated treatment regimen (definitive-dose radiotherapy [RT] of 50-61.2Gy, with/without chemotherapy) for these patients, and predictors of progression-free survival (PFS) and overall survival (OS). Between 2006 and 2018, 44 consecutive patients (42 men and 2 women; median age, 70years) who underwent definitive-dose RT post-ESD and had a pathological depth of the muscularis mucosa with lymphovascular invasion (LVI) or the upper-middle submucosal third at our institution were included. We excluded patients who could not obtain a margin-free resection by ESD. If feasible, systemic chemotherapy with 5-fluorouracil plus high- or low-dose cisplatin or nedaplatin was administered concurrently. Five-year PFS, OS, and disease-specific survival rates were 78.8%, 88.4%, and 97.7%, respectively. Six metachronous esophagus (14%), two locoregional LN within the irradiated area with a prophylactic dose of 41.4Gy (5%), and two locoregional LN plus liver (5%) recurrences occurred. No LN recurrence occurred within the definitive dose of ≥ 50Gy in the irradiated area. Metachronous esophageal recurrence involved areas receiving ≥ 50Gy. Univariate and multivariate analyses revealed that age was an independent prognostic factor for both PFS and OS. Definitive-dose RT/CRT post-ESD could provide favorable locoregional LN control and PFS/OS regardless of patient characteristics, including pathological findings and chemotherapy regimen/course, except for age. These results need to be interpreted carefully given several limitations, therefore, definitive-dose RT/CRT should be conducted with caution in clinical practice until high-quality prospective clinical trials evaluating the effectiveness and safety.

Real-World Survival Impact and Utilization of Adjuvant Radiation in Advanced Laryngeal Cancer.

Background: Optimal treatment of locally advanced cancer of the larynx is controversial. In this study, we aim to compare outcomes in patients with T3-4N0-1 cancer of the larynx who underwent surgery alone versus surgery followed by radiation therapy (RT). Materials and Methods: A total of 1820 patients with advanced laryngeal cancer were identified from the national Surveillance, Epidemiology, and End Results Database and stratified based on postoperative RT status, and clinical outcomes were compared between these 2 groups. Propensity score matching was conducted to balance baseline characteristics. Results: The majority of patients (53.4%) received adjuvant RT. N0 patients who received laryngectomy and who did not undergo adjuvant radiation had a 47% higher risk of cancer-specific death than patients receiving adjuvant RT (adj. HR 1.47, 95% CI 1.18-1.84). N1 patients who did not undergo adjuvant radiation had a 90% higher risk of cancer-specific death than patients receiving RT after surgery (adj. HR 1.90, 95% CI 1.27-2.84). After adjusting for propensity scores, adjuvant RT carried a significant overall survival benefit (HR 0.73, 95% CI 0.60-0.87). Conclusions: This study provides real-world support for adjuvant radiation in patients with T3-4N0-1 laryngeal carcinoma. Nearly half of patients did not receive RT, indicating a need for national provider education and process improvement strategies to improve utilization.