Presence Of Metastases Research Articles

QLTI-20. BRIDGING THE GAP: UNDERSTANDING THE CURRENT TREATMENT RESPONSES TO ENHANCE THE STANDARD OF CARE AND OUTCOMES FOR MALIGNANT PERIPHERAL NERVE SHEATH TUMORS

Abstract Malignant peripheral nerve sheath tumor (MPNST) are a rare and aggressive cancer that make up 5-10% of all sarcomas. There is currently no effective targeted therapy to treat MPNST and surgical resection remains the mainstay of treatment, though often not feasible due to location, size of the tumor, or presence of metastases. Evaluation of MPNST treatment response to palliative chemotherapy regimens could serve as a reference point for target response rates in clinical trials going forward. We performed a retrospective electronic health record analysis of patients with biopsy-proven diagnoses of MPNST at Washington University and Johns Hopkins University. We evaluated tumor characteristics along with treatment response, overall survival (OS), and progression free survival (PFS) rates for different chemotherapeutic regimens. The cohort comprises 140 patients, with ages at diagnosis ranging from 21 to 40 years. Most patients had tumors located in the extremities, with sizes ranging from 5-10 cm at the time of diagnosis. We identified 66 patients who received adjuvant chemotherapy, 44 received neoadjuvant chemotherapy and 28 did not receive any chemotherapy. We will present objective response rate (ORR) and clinical benefit rate (CBR) for neoadjuvant chemotherapy. Among patients with metastatic disease (n=53), 12 chemotherapy regimens were assessed. All regimens other than gemcitabine-docetaxel chemotherapy regimen performed better than the median PFS of 1.77 months which has been observed in clinical trials of targeted agents to date with the most compelling response to vincristine-irinotecan-temozolomide regimen. Despite advancements in our understanding of MPNST pathogenesis, these tumors carry a poor prognosis. Our study has identified several systemic therapies which should be further evaluated prospectively to improve treatment options and outcomes for patients with this aggressive sarcoma. These results can serve as a benchmark for future clinical trials.

PSMA PET/CT Accuracy in Diagnosing Prostate Cancer Nodes Metastases.

This study aimed to evaluate the diagnostic accuracy of prostate-specific membrane antigen (PSMA)-directed positron emission tomography/computed tomography (PET/CT) in pelvic nodal staging, using postoperative histopathology data as the reference standard. From January 2020 to June 2024, 78 patients with clinically significant prostate cancer (PCa) (ISUP Grade Group 2) underwent radical prostatectomy plus extended pelvic lymph node dissection (ePLND): 60 (77%) vs. 18 (23%) men had an intermediate vs. high risk PCa. All the patients underwent PSMA PET/TC before surgery for clinical staging and nodes focal uptake (standardized uptake value "SUVmax) was evaluated to rule out the presence of metastases. PSMA PET/CT was suspicious for nodes metastases in 16/78 (20.5%) men (median SUVmax 26.2), conversely, histology demonstrated nodes metastases in 18/78 (23.1%). PSMA PET/CT was negative for nodal involvement in all Grade Group 2 (GG2) PCa, positive in 4/4 (100%) GG3 PCa, and in 10/14 (71.4%) GG5 PCa. In detail, PSMA PET/CT was false negative in 2/4 PCa, characterized by GG5 plus ductal adenocarcinoma. Overall, PSMA PET/CT sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy in diagnosing nodal metastases were equal to 87.5, 96.8, 87.5 96.7, and 92.3%, respectively. PSMA PET/CT demonstrated an overall diagnostic accuracy of 92.3% in nodal staging (100% in GG2 PCa), which decreased to 63.6% in GG5 PCa. In high-risk patients or in case of ductal adenocarcinoma, a negative PSMA PET/CT does not rule out the need for ePLND.

Falls and fractures in men with prostate cancer taking second-generation androgen receptor antagonists: A retrospective chart review.

Second-generation androgen receptor antagonists, including enzalutamide, apalutamide, and darolutamide, are commonly used to treat metastatic and non-metastatic prostate cancer. Although these medications are typically well-tolerated, falls were reported in 4.2-15.6% of patients and fractures in 4.2-11.7% of patients enrolled in the phase III clinical trials evaluating these drugs in prostate cancer. However, post-marketing studies have reported a lower incidence than reported in clinical trials. The objective of this study is to determine the prevalence of falls and fractures in patients with prostate cancer receiving second-generation androgen receptor antagonists at UConn Health and identify potential risk factors associated with falls and fractures in these patients. A retrospective chart review involving patients with prostate cancer treated with darolutamide, enzalutamide, or apalutamide from March 1, 2022, to March 31, 2023, at UConn Health Carole & Ray Neag Comprehensive Cancer Center. Data recorded includes basic demographics, history of fall or fracture, presence of metastases, fall risk, history of osteoporosis, prescribed second-generation androgen receptor antagonist, and other comorbidities. Data was evaluated using descriptive statistics. Twenty-six men were included, all of whom were receiving enzalutamide. At baseline, 96.1% of patients had bone metastases, 15.4% had osteoporosis, 15.4% had osteopenia, and 34.6% had neuropathy. The incidence of falls was 19.2% and the incidence of fractures was 26.9%. The mean length of therapy at time of a fall was 19.44 months (range, 6-31 months). The mean length of therapy at time of a fracture was 19 months (range, 1-33 months). In patients experiencing fall, 100% had arthralgia, 60% had neuropathy, 40% had a gait problem, 40% had hypertension, and 80% of them were at risk of fall. In patients experiencing fracture, 28.6% had osteoporosis, 42.9% had osteopenia, 100% had bone metastases, and 57.1% were on denosumab at time of fracture. The prevalence of falls and fractures in patients receiving enzalutamide were higher in this retrospective chart review than reported in clinical trials and post-marketing studies. This could be due to the small patient population or the patient's comorbidities such as osteoporosis, bone metastases, or neuropathy. Fall/fracture risk with enzalutamide and other risk factors for fall and fracture should be considered when discussing treatment and developing a monitoring plan.

Sarcomas of the Head and Neck Region

Introduction: Sarcomas are relatively rare malignant tumors of mesenchymal origin, representing only about 1% of tumors in the head and neck region. Materials and Methods: A retrospective study involved patients with sarcomas of the head and neck region who were diagnosed and treated over a 5-year period. Results: Nine patients were included, 4 men and 5 women. The mean age of the patients was 51 years. Eight patients had soft tissue sarcomas, and 1 patient had osteosarcoma. The most common histologic types were dermatofibrosarcoma protuberans and angiosarcoma. Tumors presented predominantly with local symptomatology. All patients were treated only by surgical excision. No distant or regional metastases were found in any patient. Complete surgical excision was achieved in all cases, except in patients with chondrosarcoma of the nose and sinuses, who died due to local progression in the second year of follow-up. Other patients were disease-free during the observed period; a patient with osteosarcoma died in the fourth year of follow-up without recurrence of the malignant disease. Conclusion: Large prospective and multicenter studies are necessary to provide relevant data on the distribution of different types of sarcoma in the head and neck region, their clinical behavior and response to therapeutic modalities, as well as on recurrence, presence of metastases, and survival.

Significance of apparent diffusion coefficient in diagnosis of rectal carcinoma.

The apparent diffusion coefficient (ADC) is a quantitative parameter that facilitates the detection and reliable differentiation of rectal cancer. MR differentiation between rectal carcinoma, post-radiation proctitis, and normal rectal wall with the ADC values and their comparison depending onthe level of tumor markers and pathohistological characteristics of rectal carcinoma. The retrospective study performed at the Oncology Institute of Vojvodina included 300 patients, 100 each with rectal cancer, post-radiation proctitis, and normal rectum. Mean ADC values were obtained by measuring the region of interest (ROI) of the rectal wall. Rectal cancer showed lower ADC values (0.665 ± 0.086 x 10-3mm2/s) compared to both post-radiation proctitis (1.648 ± 0.268 x 10-3mm2/s) and normal rectum (1.180 ± 0.110 x 10-3mm2/s) (p<0.001). No significant differences in ADC values were observed between different grades of rectal cancer (p=0.874; p>0.05), depending on the presence of metastases in the lymph nodes (p=0.357; p>0.05), different TN stage (p=0.196; p>0.05), local spread of the tumor (p=0.312; p>0.05), the presence of RAS mutation (p=0.829; p>0.05) and the value of tumor markers (p=0.923; p>0.05). ADC values below 1.013 x 10-3mm2/s with 100% sensitivity and 96% specificity indicate the presence of rectal cancer in relation to normal wall, with a positive predictive value of 96.1% and a negative of 100%. ADC values below 1.255 x 10-3mm2/s with 100% sensitivity and 95% specificity indicate rectal cancer in relation to post-radiation proctitis. ADC values above 1.339 x 10-3mm2/s with 87% sensitivity and 89% specificity indicate post-radiation proctitis in relation to normal wall. The ADC is a useful marker in differentiating between rectal cancer, post-radiation proctitis, and normal rectal wall with high sensitivity and specificity, but it cannot be used to distinguish the histological grades of rectal cancer, nor other pathohistological parameters.

Analysis of progression-free and overall survival in ovarian cancer: Bevacizumab treatment outcomes using historical cohort.

Background: The incorporation of bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor (VEGF), has redefined therapeutic strategies for advanced ovarian cancer. This study evaluates the efficacy of bevacizumab combined with standard chemotherapy by comparing progression-free survival (PFS) and overall survival (OS) outcomes with a historical cohort of patients treated with standard chemotherapy alone. Methods: We conducted an analysis of 71 patients with advanced epithelial ovarian cancer treated at the University Clinical Center in Niš, Serbia, from April 2017 to March 2023. All patients received standard chemotherapy paired with bevacizumab and were monitored for progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier estimates. Subgroup analyses were performed based on age, ECOG performance status, presence of metastases, and pleural effusion. Additionally, a historical cohort of 30 patients treated with standard chemotherapy alone was used for comparison, and Cox regression analysis was conducted to identify factors influencing treatment outcomes. Results: The study findings indicate significant improvements in median PFS (20 months vs. 15 months) and OS (58 months vs. an undetermined upper limit) compared to the historical cohort. Subgroup analysis of the bevacizumab-treated group revealed that younger patients (<65 years) and those without metastases or pleural effusion exhibited notably better survival outcomes. The hazard ratio for PFS in patients younger than 65 was 0.65 (95% CI: 0.45-0.93), suggesting a substantial reduction in disease progression risk compared to older patients. Conclusion: Bevacizumab, when used alongside standard chemotherapy, significantly extends both PFS and OS in patients with advanced ovarian cancer. These benefits are particularly pronounced in younger patients. The results underscore the necessity of integrating bevacizumab into the treatment regimen for advanced ovarian cancer, advocating for tailored therapeutic strategies based on individual risk profiles and clinical characteristics. This study reinforces the pivotal role of bevacizumab in enhancing the current ovarian cancer treatment landscape and highlights the potential for further personalizing oncological care.

Head and neck sarcomas: Thirty years of experience in a tertiary referral center in Brazil.

This study analyzed the demographics, clinicopathological, treatment, and survival characteristics of head and neck sarcomas (HNS) diagnosed in a tertiary reference center in Brazil. HNS cases were retrospectively retrieved from the Department of Pathological Anatomy of the School of Medical Sciences of the State University of Campinas. The medical records were examined to extract demographic, clinicopathological, and follow-up information. The Pearson chi-square test, Kaplan-Meier curve, and Cox proportional hazards regression model were employed to identify survival and potential prognostic factors. A total of 47 patients were included in the study. The majority were men (61.7%) with a mean age of 38.9 years. The nasal cavity (34.0%) was the most common anatomical site. The lesions are usually presented as volume increases (78.7%). The most common histological subtypes were chondrosarcoma, osteosarcoma, and alveolar rhabdomyosarcoma. Surgical excision alone was the most common treatment modality. Local recurrence was observed in 10 cases, and metastases in 3 cases. During a mean follow-up period of 71.9 months, from diagnosis to the last follow-up, 31 patients (65.9%) were alive without the disease. A total of 10 patients (21.3%) died of the HNS for a mean follow-up period of 14.3 months. The time to presentation of more than 6 months (p = 0.0309) and the presence of metastases (p = 0.0315) were identified as prognostic factors for survival, while male sex was found to be an independent prognostic factor for recurrence. In conclusion, the results of this study indicate that the occurrence of a shorter lesion time to presentation and the presence of metastases were associated with a reduction in survival rates in patients with HNS.

Constitutional mosaicism of pathogenic variants in SMARCB1 in a subset of patients with sporadic rhabdoid tumors.

Malignant rhabdoid tumors are aggressive malignancies predominantly affecting very young children. The characteristic genetic alteration is biallelic inactivation of SMARCB1. In approximately 30% of patients one SMARCB1 allele is constitutionally altered conferring a particularly unfavourable prognosis. Constitutional mosaicism for pathogenic SMARCB1 mutations has recently been reported in distinct cases of allegedly sporadic rhabdoid tumors. We aimed to systematically investigate the frequency and clinical impact of constitutional mosaicism in patients with sporadic rhabdoid tumors included in the EU-RHAB registry. We selected 29 patients with rhabdoid tumors displaying at least one pathogenic small variant in SMARCB1 in the tumor DNA and absence of a germline mutation. We re-screened blood-derived patient and control DNA for the respective small variant by PCR with unique molecular identifiers and ultra-deep next generation sequencing. Clinical data in patients with and without mosaicism and 174 EU-RHAB controls were compared. Employing an ultra-deep sequencing approach, we detected tumor-associated SMARCB1 variants in blood-derived DNA in 9/29 patients. In 6/29 patients (21%), whose variant allele frequency (VAF) exceeded 2%, constitutional mosaicism was assumed whereas tumor DNA contamination was documented in 1/3 patients with VAF below 1%. No significant differences were observed between 6 mosaic-positive and 20 -negative patients regarding age at diagnosis, presence of metastases, event-free or overall survival. Constitutional mosaicism for pathogenic small SMARCB1 variants is recurrent in patients with allegedly sporadic rhabdoid tumors. The clinical implications of such variants need to be determined in larger, prospective cohorts also including detection of structural variants of SMARCB1.

Clinical, imaging and pathological features of extraskeletal myxoid chondrosarcoma.

To evaluate clinical and radiological features of extraskeletal myxoid chondrosarcomas (EMC). Our pathology database was queried for cases of EMCs. Tumor location, size, imaging appearance, presence of metastases, disease recurrence, and clinical outcome were documented. Imaging studies were evaluated in consensus by a musculoskeletal radiologist and an orthopedic oncologist. Thirty subjects met the inclusion criteria (mean age 52.7 ± 16.2years; 19 male, 11 female), 17 (56.7%) of which had pre-operative imaging. Tumors occurred most often in the lower extremities (20/30; 66.7%). All cases presented as a soft-tissue mass without mineralization on XR or CT. On MRI, tumors were typically hyperintense on T2-weighted sequences (14/14; 100%) and had a chondroid matrix appearance (12/14; 85.7%). Tumor invasion was observed in 11 out of 16 (68.9%) patients and necrosis in 2 out of 11 subjects (18.2%). All subjects had their tumors examined by pathology, and 20 (66.7%) subjects also had descriptive information in addition to the diagnosis (tumor invasion, mitotic rate, and necrosis) noted in the pathology reports. The mean duration of follow-up was 9.4 ± 7.5 (1.0 - 29.6) years. At the last follow-up, 14 out of 28 (50%) subjects were disease-free, 6 out of 28 had persistent metastatic disease and 8 out of 28 had died. EMC is a rare sarcoma that commonly presents as lower extremity soft tissue mass with chondroid appearance on MRI. Unlike conventional chondrosarcomas, EMC do not demonstrate mineralization on XR or CT.

Autofluorescent Cancer Stem Cells: Potential Biomarker to Predict Recurrence in Resected Colorectal Tumor.

Cancer stem cells (CSCs) in colorectal cancer (CRC) drive intratumoral heterogeneity and distant metastases. Previous research from our group showed that CSCs can be easily detected by autofluorescence (AF). The aim of the present study was to evaluate the potential role of AF CSCs as a prognostic biomarker for CRC relapse. Seventy-five freshly-resected tumors were analyzed, by flow cytometry. AF was categorized as high (H-AF) or low (L-AF), and results were correlated with histological features (grade of differentiation, presence of metastases in lymph nodes (LN), perivascular and lymphovascular invasion) and clinical variables (time to relapse and overall survival). Nineteen out of 75 (25.3%) patients experienced relapse (local or distant), 13 out of these 19 patients showed positive LNs and 6 patients had H-AF. Of note, 4 of them died before 5 years. While patients with H-AF CSCs percentages in the global population experienced 1.5 times increased relapse -HR 1.47, CI 95% (0.60 - 3.63), patients with H-AF CSC percentages and LN metastases had the highest risk of relapse; HR 7.92, p< 0.004, CI 95% (1.97 - 31.82). These data support AF as an accurate and feasible marker to identify CSCs in resected CRC. A strong statistical association between H-AF CSCs and the risk of relapse was observed, particularly in patients with positive LNs, suggesting that H-AF patients might benefit from adjuvant chemotherapy regimens and intensive surveillance due to their high propensity to experience disease recurrence.

Clinical and Prognostic Characteristics in Childhood Osteosarcoma: A Single-Center Experience in Türkiye.

In our study, we aimed to share the clinical experiences of our center regarding osteosarcoma cases, the most common primary malignant bone tumor in children and adolescents. With approval from the Clinical Research Ethics Committee of our center, the data of 59 pediatric patients who were followed up in our center with the diagnosis of osteosarcoma between 2007 and 2021 were evaluated retrospectively. The mean time between the onset of symptoms and diagnosis was 3 months. Although not statistically significant, patients with a diagnostic delay of 3 months or less had a higher rate of recurrence and mortality. 59.3% of patients had metastatic disease, and the presence of metastases was associated with higher rates of recurrence and mortality. Significant number of patients had multiple surgical operations. Amputation as the first operation and the need for multiple surgeries were associated with higher mortality. Pathologically poor response to chemotherapy is associated with mortality. 42.4% of patients died, and the 5-year overall and disease-free survival rates were 47.5% and 30.5%, respectively. Survival rates were highest in non-metastatic and non-relapsed patients, and lowest in metastatic patients and patients with poor response to chemotherapy. Renal problems and cardiotoxicity were most frequently treatment-related complications. Significant improvements have been achieved in the survival and quality of life in osteosarcoma cases compared to previous years; however, there is still a long way to go, and more multicenter and multidisciplinary studies are needed on osteosarcoma.

Molecular alterations in mucinous ovarian tumors – a review

Abstract Mucinous ovarian tumors (MOTs) include primary and secondary neoplasms, the latter of which contribute for 80% of all cases. The most common site of origin for secondary MOTs is the gastrointestinal tract. Proper differentiation between primary and metastatic lesions is essential for effective treatment. Currently, definitive diagnosis is made based on post-operative histopathological examination with the use of immunohistochemical markers. However, the final diagnosis presents a challenge because of the histopathological similarity between mucinous metastases and primary ovarian lesions. Generally, treatment consists of cytoreductive surgery and adjuvant chemotherapy, even though malignant tumors are found to be chemo-resistant. Prognosis depends on the type of the tumor, presence of metastases and patient’s general condition. Further research on the genetic background of MOTs is necessary for the better understanding of their origin and more effective treatment. This review aims to summarize recent advances in the field of the molecular features of MOTs and their implications for the diagnostic pathways and potential adjuvant therapy options. The analysis of molecular alterations might not only be an important prognostic factor, but also a useful diagnostic tool in distinguishing between primary mucinous tumors and extra-ovarian metastases or other subtypes of epithelial ovarian neoplasms. Moreover, the examination of genetic mutations seems to increase the efficiency of targeted therapy. However, more research evaluating such therapies in pre-clinical models is needed to improve the results of the diagnostics and treatment of MOTs.

Contemporary surgical management of pediatric non-rhabdomyosarcoma soft tissue sarcoma.

Non-rhabdomyosarcoma soft tissue sarcoma (STS) comprises most STS in pediatric patients. It is a diverse set of over 30 histologic subtypes. Treatment is based on risk group determined by tumor size, grade, and the presence of metastases. Surgical resection is a cornerstone of therapy, as tumors are often resistant to chemotherapy or radiation. While patients with isolated tumors less than 5cm may undergo upfront resection, strong consideration should be given to neoadjuvant chemoradiotherapy to ensure negative margins at surgical resection and optimal outcomes. Sentinel lymph node biopsy is strongly recommended for clear cell and epithelioid sarcomas. The most common metastatic site is the lung, and metastases should be resected at the end of therapy, when feasible. Unfortunately, many high-risk patients progress on therapy, and alternative strategies including earlier metastatic control require investigation.

Systemic Treatment Strategies and Outcomes of Patients With Synchronous Peritoneal Metastases of Gastric Origin: A Nationwide Population-Based Study.

Palliative systemic treatment is currently standard of care for metastatic gastric cancer. However, patients with peritoneal metastases of gastric origin are often underrepresented in clinical studies due to unmeasurable radiologic disease. This study describes the systemic treatment strategies and outcomes in patients with peritoneal metastases in a nationwide real-world setting. Patients with gastric adenocarcinoma and synchronous peritoneal metastases (with or without other metastases) diagnosed in the Netherlands between 2015 and 2020 were identified from the nationwide Netherlands Cancer Registry. Median overall survival (OS) and time-to-treatment failure were determined and multivariable Cox regression analyses were used to compare treatment groups, corrected for relevant tumor and patient characteristics. In total, 1,972 patients were included, of whom 842 (43%) were treated with palliative systemic therapy. The majority received capecitabine + oxaliplatin (CAPOX; 44%), followed by fluorouracil/leucovorin/oxaliplatin (FOLFOX; 19%), and epirubicin + capecitabine + oxaliplatin (EOX; 8%). Of the 99 (45%) patients who received second-line systemic treatment, ramucirumab + paclitaxel were administered most frequently (63%). After adjustment for sex, age, comorbidities, performance status, tumor location, Lauren classification, and the presence of metastases outside of the peritoneum, patients treated with a triplet containing docetaxel and those treated with a regimen containing trastuzumab had a significantly longer OS compared with patients treated with a doublet containing a fluoropyrimidine derivate + oxaliplatin (hazard ratio [HR], 0.69; 95% CI, 0.52-0.91, and HR, 0.68; 95% CI, 0.51-0.91, respectively). Monotherapy was associated with a shorter OS (HR, 2.08, 95% CI, 1.53-2.83). There is substantial heterogeneity in systemic treatment choices in patients with gastric cancer and peritoneal metastases in the Netherlands. In this study, patients treated with triplets containing docetaxel and with trastuzumab-containing regimens survived longer than patients who received doublet therapy. Despite this, median OS for all treatment groups remained below one year.

The landscape of cancer-associated transcript fusions in adult brain tumors: a longitudinal assessment in 140 patients with cerebral gliomas and brain metastases.

Oncogenic fusions of neurotrophic receptor tyrosine kinase NTRK1, NTRK2, or NTRK3 genes have been found in different types of solid tumors. The treatment of patients with TRK fusion cancer with a first-generation TRK inhibitor (such as larotrectinib or entrectinib) is associated with high response rates (>75%), regardless of tumor histology and presence of metastases. Due to the efficacy of TRK inhibitor therapy of larotrectinib and entrectinib, it is clinically important to identify patients accurately and efficiently with TRK fusion cancer. In this retrospective study, we provide unique data on the incidence of oncogenic NTRK gene fusions in patients with brain metastases (BM) and gliomas. 140 samples fixed and paraffin-embedded tissue (FFPE) of adult patients (59 of gliomas [17 of WHO grade II, 20 of WHO grade III and 22 glioblastomas] and 81 of brain metastasis (BM) of different primary tumors) are analyzed. Identification of NTRK gene fusions is performed using next-generation sequencing (NGS) technology using Focus RNA assay kit (Thermo Fisher Scientific). We identified an ETV6 (5)::NTRK3 (15) fusion event using targeted next-generation sequencing (NGS) in one of 59 glioma patient with oligodendroglioma-grade II, IDH-mutated and 1p19q co-deleted at incidence of 1.69%. Five additional patients harboring TMPRSS (2)::ERG (4) were identified in pancreatic carcinoma brain metastasis (BM), prostatic carcinoma BM, endometrium BM and oligodendroglioma (grade II), IDH-mutated and 1p19q co-deleted. A FGFR3 (17)::TACC3 (11) fusion was identified in one carcinoma breast BM. Aberrant splicing to produce EGFR exons 2-7 skipping mRNA, and MET exon 14 skipping mRNA were identified in glioblastoma and pancreas carcinoma BM, respectively. This study provides data on the incidence of NTRK gene fusions in brain tumors, which could strongly support the relevance of innovative clinical trials with specific targeted therapies (larotrectinib, entrectinib) in this population of patients. FGFR3 (17)::TACC3 (11) rearrangement was detected in breast carcinoma BM with the possibility of using some specific targeted therapies and TMPRSS (2)::ERG (4) rearrangements occur in a subset of patients with, prostatic carcinoma BM, endometrium BM, and oligodendroglioma (grade II), IDH-mutated and 1p19q co-deleted, where there are yet no approved ERG-directed therapies.

“The oncologist told me”: Reported speech as a patients’ resource to volunteer concerns in oncological visits

Based on the “patient centered approach”, growing emphasis within policies has been put on patients' active participation in medical encounters. Consistently, research has investigated patients' initiatives during medical visits in a wide array of settings and specialties. Among these, oncological care constitutes a setting where patient participation is particularly crucial as well as challenging. However, previous studies in this setting have focused mainly on doctors' interactional work, with few works exploring patients' expressions of fears, uncertainties, and hopes. The present study contributes to this underexplored line of inquiry by showing how oncological patients take the initiative and make relevant their concerns through reported speech (RS). Based on a corpus of 106 video-recorded oncological visits collected in Italy and adopting conversation analysis, the article shows how patients use RS to volunteer some information they have previously been told by other, non-present physicians. Through RS, patients cautiously make relevant specific aspects of their case that have not been addressed in the ongoing interaction and appear to constitute a concern for them (e.g., presence of metastases, treatment side effects, hospitalization length). In response, the physician addresses the patient's concern, either by confirming the reported information or by distancing themselves from it, thus providing their opinion on the matter.

Radiation-Induced DNA Damage in Uveal Melanoma Is Influenced by Dose Delivery and Chromosome 3 Status.

The purpose of this study was to analyze the extent of DNA breaks in primary uveal melanoma (UM) with regard to radiotherapy dose delivery (single-dose versus fractionated) and monosomy 3 status. A total of 54 patients with UM were included. Stereotactic radiotherapy (SRT) was performed in 23 patients, with 8 undergoing single-dose SRT (sdSRT) treatment and 15 receiving fractionated SRT (fSRT). DNA breaks in the enucleated or endoresected tumors were visualized by a TUNEL assay and quantified by measuring the TUNEL-positive area. Protein expression was analyzed by immunohistochemistry. Co-detection of chromosome 3 with proteins was performed by immuno-fluorescent in situ hybridization. The amount of DNA breaks in the total irradiated group was increased by 2.7-fold (P < 0.001) compared to non-irradiated tissue. Tumors treated with fSRT were affected more severely, showing 2.1-fold more DNA damage (P = 0.007) compared to the cases after single (high) dose irradiation (sdSRT). Monosomy 3 tumors showed less DNA breaks compared to disomy 3 samples (P = 0.004). The presence of metastases after radiotherapy correlated with monosomy 3 and less DNA breaks compared to patients with non-metastatic cancer in the combined group with fSRT and sdSRT (P < 0.05). Fractionated irradiation led to more DNA damage than single-dose treatment in primary UM. As tumors with monosomy 3 showed less DNA breaks than those with disomy 3, this may indicate that they are less radiosensitive, which may influence the efficacy of irradiation.

CINSARC score use in pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS) in the Children’s Oncology Group (COG) studies ARST0332 and ARST1321.

10013 Background: Despite genomic and histologic heterogeneity, limited risk stratification is used in the treatment of NRSTS (grade, size, presence of metastases, and extent of surgical resection). Genomic signatures including CINSARC score and Genomic Index (GI), both measures of genomic instability, have been shown to be prognostic in retrospective studies, but are not routinely used clinically. Here we evaluated the association of these scores with EFS and OS on two consecutive, prospective COG NRSTS studies, ARST0332 and ARST1321. Methods: All patients enrolled to ARST0332 or ARST1321 with sufficient banked tumor in the COG biospecimen repository were included in this analysis. Whole exome and transcriptome sequencing was performed on DNA and RNA from banked FFPE and flash frozen specimens. Raw WES reads were mapped to hg38 using BWA. The base qualities of the aligned reads were recalibrated and realigned by GATK. RNAseq data was aligned to hg38 by STAR. Differential expression analysis was performed by DESeq2. Stratified log rank and proportional hazards models were used to evaluate the association of CINSARC score and GI above or below the median with EFS and OS. Results: Tumors from 197 patients yielded sufficient DNA and 166 sufficient RNA, of which 177 and 142, respectively, passed sequencing quality metrics and were included. Demographics of these patients were generally representative of overall trial enrollment with most patients between ages 10-17 years (53%) with localized disease (77-80%). The most common histologic diagnoses were synovial sarcoma (35-37%) and MPNST (9-12%). Median follow-up was 6 years. CINSARC high vs low was associated with worse EFS (5-year 52.1% vs 74.6%, p &lt; 0.01) and OS (5-year 66.2% vs 83.6%, p &lt; 0.01). Accounting for sex and presence of metastatic disease, the hazard ratio for CINSARC high was 2.4 for EFS and 2.7 for OS (p &lt; 0.01). CINSARC maintained the association with EFS among patients with non-metastatic disease (p = 0.017), and with OS among patients with metastatic disease (p = 0.031). GI analysis is ongoing and will be reported. Conclusions: In this analysis from the largest prospective North American pediatric NRSTS studies to date, CINSARC score was prognostic for EFS and OS. Further analysis including additional clinical prognostic factors (tumor size, grade, and extent of resection) is ongoing and will be reported. Use of CINSARC score for risk stratification should be considered on future NRSTS clinical trials. Clinical trial information: NCT00346164 , NCT02180867 .

Radiomic survival prediction with liver metastases in colorectal cancer.

e15584 Background: The survival outcome of colorectal cancer depends upon staging and the presence of metastases. Nonetheless, there isn’t a reliable prediction model for overall survival (OS) specifically tailored to patients with colorectal cancer who have liver metastases. Consequently, this study aims to find radiomic features that can be utilized to predict OS of colorectal cancer with liver metastases. Methods: We utilized the Colorectal Liver Metastases data set in The Cancer Imaging Archive (TCIA). Overall, 197 patients with colorectal cancer metastatic to the liver were identified. Semi-automatic segmentation of liver metastases was used to extract radiomic features including Gray-Level Co-occurrence (glcm), Gray-Level Run Length Matrix (glrlm), Gray-Level Size Zone Matrix (glszm), Gray-Level Dependence Matrix (gldm), and Neighborhood Gray-Tone Difference Matrix (ngtdm). 3D Slicer was used to extract radiomic features. We tested a Cox proportional hazards model in each radiomics feature to predict OS. Results: Total 107 radiomic features were extracted from pre-segmented liver metastases on patients’ Computed Tomography images. Among them, original shape sphericity, original glcm correlation, original gldm DependenceEntropy, and original glrlm RunEntropy were statistically significant for the prediction of OS, with a hazard ratio of -2.16 (CI 0.01-0.92; p value 0.04), 1.54 (CI 1.5-14.0; p value 0.006), 0.51 (CI 1.0-2.5; p value 0.02), and 0.52 (CI 1.0-2.6; p value 0.03), respectively. Conclusions: Our data analysis indicates crucial radiomic features that hold promise for predicting the clinical outcome of patients with colorectal cancer who have liver metastases. Future research with a larger sample size is warranted for the external validation of our results.

Efficacy of First-Line Treatment With Pertuzumab and Trastuzumab in Advanced Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer in Routine Clinical Practice.

The first-line treatment for human epidermal growth factor receptor 2-positive (HER2+) metastatic breast cancer (MBC) involves a combination of trastuzumab, pertuzumab, and a taxane (TPH). This study assessed the efficacy of trastuzumab and pertuzumab (PH) in routine practice, following the treatment protocols of Uruguay's National Resources Fund (FNR), akin to clinical trials. Patients with advanced MBC treated with PH between 2008 and 2022 per FNR protocols were evaluated. The Kaplan-Meyer method and log-rank test were utilized for analyzing overall survival (OS). Demographic and clinical variables, including age, menopausal status, and hormone receptors (HR), were analyzed. The study included 318 PH-treated patients. The median age was 56 years, with 63.2% being postmenopausal and 60.4% HR and HER-2 positive. With a median follow-up of 17.2 months, the median OS was 29 months. OS varied based on HR status and the presence of metastases at different sites, significantly lower in patients with brain, cutaneous/subcutaneous, and pulmonary metastases. Additionally, OS was higher in patients treated at private institutions compared to public ones. This study demonstrates the disparity in oncological treatment efficacy between clinical trials and clinical reality in Uruguay, emphasizing the importance of authentic environment research for more representative and effective medicine in Latin America.