Presence Of Metastatic Disease Research Articles

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 < 0.01) and OS (5-year 66.2% vs 83.6%, p < 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 < 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 .

Long-term survival of patients with lung cancer with kinase fusions (KF) treated at a tertiary community-based cancer program.

e23279 Background: Comprehensive Genomic Profiling (CGP) has been routinely obtained on patients with advanced cancers without standard-of-care therapeutic options managed in our community-based cancer program for more than a decade. Methods: In 2018, we reported that 1% (77 of 7,260 pts) who underwent CGP (Foundation Medicine Inc. hybrid capture based CGP platform) were found to have a KF abnormality (median age 53), including 55 patients (pts) (71%) with non-small cell lung cancer (NSCLC) and 22 (29%) with other malignancies. The incidence of KF in the NSCLC population tested was approximately 5%. Of the 55 patients with NSCLC, 36 pts (65%) had ALK fusions, 12 pts (22%) has RET fusions, 7 pts (13%) had ROS1 fusions. Results: This report describes long-term survival of NSCLC pts with metastatic disease within this population treated with KF targeted therapy for > 5 years. Five pts (9% of NSCLC with a KF; all females; median age 63 [range 57-72]) remain on active therapy a median of 10 years (range 6.5-12 years) from the initiation of therapy. 2 pts have EML4-ALK fusions, 1 pt has EZR-ROS1 fusion, 1 pt has CD74-ROS1 fusion, and 1 pt has ALK PRKAR1A fusion. 2 of 5 pts have continued their initial KF agent while 2 switched >1 times to an alternative KF targeted drug and 1 is currently receiving chemotherapy. Only two pts had the identical KF abnormality. Conclusions: In this series approximately 10% of NSCLC pts with a KF experienced extended survival (greater than five years) despite the presence of metastatic disease, including three patients with brain mets. It is critical to conduct molecular testing on all NSCLC pts for the presence of a kinase fusion abnormality. Treatment directed at this molecular target can result in long-term survival.

Radioactive iodine refractoriness in Middle Eastern differentiated thyroid cancer: clinical outcome and risk factor analysis.

Radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) has received increasing attention due to its poor prognosis. However, outcomes may vary among patients with RAIR-DTC. The role of clinico-pathological and molecular prognostic factors in survival remains controversial, resulting in difficulty in selecting patients for new targeted therapies. We assessed mortality rate and DTC-specific survival in Middle Eastern RAIR-DTC to identify prognostic factors associated with survival. This single center, retrospective study enrolled 268 patients with RAIR-DTC. Mortality rate and DTC-specific survival were analyzed to identify prognostic factors related to survival. Univariate and multivariate analysis were performed using Cox proportional hazards model. Of the 268 cases of RAIR-DTC, 40.3% (108/268) had absent 131I uptake (either on diagnostic or post-therapy whole body scan), 15.3% (41/268) had progressive disease (PD) despite 131I, 7.5% (20/268) had persistent disease despite cumulative activity of I131 of >600 mCi and 36.9% (n=99/268) developed distant metastasis. On multivariate analysis, age (more than 45 years), presence of metastatic disease and tumors harboring telomerase reverse transcriptase (TERT) promoter mutations were independent prognostic factors for poor DTC-specific survival. Subjects were divided into 3 groups according to the number of risk factors; low risk (no risk factors); intermediate (≤ 2 risk factors); and high risk (all the 3 risk factors). Ten-year DTC-specific survival rates in low, intermediate and high-risk groups were 100.0%, 92.9% and 53.6%, respectively. The contribution of age greater than 45 years to RAIR-DTC mortality is impactful. Older age, presence of distant metastasis and TERT mutations could be used as early predictors of RAIR-DTC cases. The identification of prognostic factors for poor survival in RAIR-DTC may improve the selection of patients for more personalized surveillance and therapeutic modalities.

Abstract PO2-05-11: Patient Perspectives on the Value of Stereotactic Body Radiotherapy (SBRT) in the Management of Breast Cancer: The PERSPECTIVE Study

Abstract Background: Oligometastatic disease describes limited metastases amenable to local therapy such as stereotactic body radiotherapy (SBRT). Within the UK National Health Service (NHS), SBRT is a standard of care for up to 3 metachronous sites of oligometastatic breast cancer (OMBC), offering high local control rates with low toxicity. The SABR-COMET study demonstrated improved progression-free survival (PFS) and overall survival (OS) with SBRT compared to standard of care in a number of oligometastatic cancers, including breast cancer [1]. Conversely, the NRG-002 trial results suggest no PFS or OS improvement with the addition of SBRT to standard systemic therapy in OMBC [2]. The OS data for this study are yet to mature and in the meantime the results of other prospective studies are awaited. As patients’ attitudes and perspectives govern their preferences around treatment decisions, it is vital to understand whether PFS and OS are the most important considerations for patients. This study aims to explore patients’ perspective on the role of SBRT in breast cancer management. Their views will help inform future trial endpoints and support clinicians to support patients with their decision making and expectations. Methods: We conducted an exploratory qualitative study with focus groups and individual interviews, to understand participants knowledge, views and opinions on SBRT in treating breast cancer. All patients were asked to watch an educational video about SBRT in advance of participating in the interviews. An interview guide with open-ended questions was developed. Breast cancer patients were recruited using a purposive sampling matrix based on the patients age, presence of metastatic disease and previous experience with radiotherapy. Each focus group had at least two moderators and all interviews were digitally recorded and then transcribed. The data were managed and coded using NVivo version 12 and analysed using a thematic analysis approach. Results: A total of 18 breast cancer patients participated in this study, with 7 (39%) having primary disease and 11 (61%) with metastatic disease. The study included two focus groups (group one = 5 patients; group two = 9 patients) and four individual interviews conducted between May and June 2023. The participants had a median age of 54 years (range 38-74). The majority of participants (83%) had previous experience with radiotherapy, with 4 (27%) having received SBRT previously for their OMBC. Only 2 (2%) patients who had not previously received SBRT were aware of it before participating in this study. Most of the patients (78%) were Caucasian and 72% had attained at least an undergraduate degree level of education. Throughout the study, three main themes emerged: theme 1 - participants experience with radiotherapy; theme 2 - interests and considerations regarding SBRT (including desired treatment outcomes) and theme 3 - willingness to consider SBRT in absence of a survival benefit. Extending their life was unanimously described as the most important desired outcome of SBRT, followed by quality of life. Other desired treatment outcomes expressed included reduction of tumour size, minimal collateral damage/side effects, relief of symptoms, avoidance of recurrence and increase in time to change of systemic therapy. Conclusion: In our study, while extension of life was a desired treatment outcome of SBRT for OMBC, all participants expressed willingness to consider SBRT for its potential benefits in local control and durable pain control, even in absence of a survival benefit.

Virtual reality for pain management in hospitalized patients with cancer: A randomized controlled trial.

Hospitalized patients with cancer often experience acute and/or chronic pain. Although virtual reality (VR) has been extensively studied across a wide range of clinical settings, no studies have yet evaluated potential impact on pain management in this patient population. Prospective randomized controlled trial at an urban academic hospital comparing VR against an active control to mitigate moderate-severe cancer disease and treatment-related pain. A total of 128 adult hospitalized patients with cancer (any tumor type) were randomized to 10 minutes of immersive VR distraction therapy or 10 minutes of two-dimensional guided imagery distraction therapy delivered by handheld tablet. Participants in the two arms were similar in age, sex, race, presence of metastatic disease, concurrent pain specialist consultation, and baseline opioid use. Although both groups experienced improved self-reported pain scores (primary outcome), those randomized to VR experienced significantly greater reduction in pain immediately after intervention compared with active control (p=.03). This difference was sustained for 24 hours as well (p=.004). Within-group analysis showed significant improvement in VR arm of pain bothersomeness (p=.05) and general distress (p=.03) as well. Among hospitalized adult patients with moderate-severe pain related to cancer and cancer therapies, VR provided more nonpharmacologic pain relief than active control and this benefit sustained long after conclusion of the intervention. Virtual reality (VR), a developing technology that immerses the user in new environments, has been shown to improve pain in different patient populations. To test the role of VR in improving pain in hospitalized patients with cancer who report moderate-severe pain, we compared the impact of a 10-minute immersive VR intervention to that of a 10-minute two-dimensional guided imagery experience to improve self-reported pain scores. We found that, although both interventions improved pain, VR did so significantly more. Moreover, participants assigned to VR had sustained improvement in pain 24 hours later.

Prognostic role of quantitative [18F]FDG PET/CT parameters in adrenocortical carcinoma

PurposeWe aimed to evaluate the prognostic potential of baseline [18F]FDG PET/CT for overall survival (OS) in patients with adrenocortical carcinoma (ACC).MethodsWe performed a retrospective analysis of 67 treatment-naïve ACC patients with available [18F]FDG PET/CT at time of initial diagnosis. Pretherapeutic PETs of primary tumors were manually segmented and quantitative parameters (maximum/mean/peak standardized uptake value (SUVmax/mean/peak), metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG, defined as TV*SUVmean) were derived. Based on a visual read, absence (M0) or presence of metastatic disease (M1) were evaluated. Kaplan–Meier and Cox regression analyses were used to determine the prognostic value of the above mentioned markers on overall survival adjusted for established prognostic markers.Results24/67 patients (36%) presented with M0 based on PET/CT, while the remaining 43/67 (64%) had M1-status. 32/67 patients died during follow-up and median OS was 48 months. In 12% of patients FDG-PET detected additional metastatic lesion not clearly visible by CT only. In univariable analysis, all quantitatively derived PET parameters failed to reach significance (P ≥ 0.1), and only PET/CT-based M1-status and Ki-67 were associated with increased mortality (M1: HR 13.89, 95% CI 4.15–86.32, P < 0.001; Ki-67 HR 1.29, 95% CI 1.16–1.42; P < 0.0001). Using multivariable Cox regression analyses, M1-status (HR 9.69, 95% CI 2.82–60.99) and Ki-67 index (HR 1.29, 95% CI 1.13–1.04; P < 0.05) remained significant associated with OS.ConclusionIn treatment-naïve ACC patients, the quantitative PET parameter failed to predict OS, but presence of metastases detected by [18F]FDG PET/CT and Ki-67 index were independently associated with shorter OS. Therefore, a simple visual PET-based read-out is of prognostic value at initial diagnosis, while time-consuming PET-based quantification can be omitted.

Stereotactic ablative radiation therapy in metastatic prostate cancer.

The evolving role of stereotactic ablative radiation therapy (SABR) as metastasis-directed therapy (MDT) for oligometastatic prostate cancer (omPCa) will be discussed. Oligometastatic disease (OMD) is an intermediate state between localized and wide-spread malignant disease. OMD has recently been spotlighted given the increasing demonstration of clinical benefit from local therapies despite presence of metastatic disease and allure of the curative potential of MDT in select cases. Among the different forms of MDT, SABR has rapidly become a widely adopted treatment modality. Significant efforts in this space have focused on omPCa, owing to its relatively indolent biology, presence of a sensitive and specific serum biomarker and recent advances in molecular imaging. While most studies have evaluated the role of SABR MDT in hormone sensitive omPCa, new emerging clinical data also suggests benefits of SABR MDT for even castration-resistant disease. Treating omPCa with SABR MDT appears to generate an efficacy signal with minimal morbidity across both hormone-sensitive and castration-resistant disease. However, additional definitive omPCa trial data are needed. Future research efforts should investigate biomarkers for this heterogeneous disease space and the role of SABR MDT in combination with systemic agents to improve upon standard of care treatments.

Infiltration of nanocarbon into the trachea during thyroidectomy surgery: case series and literature review

Introduction: The presence of metastatic disease in the cervical lymph nodes can affect the recurrence and survival of patients with thyroid cancer. Parathyroid gland injury during surgery can result in hypoparathyroidism, particularly with total thyroidectomy. Injection of carbon nanoparticles into the thyroid will label draining lymph nodes and aid in the visualization of metastatic cervical lymph nodes during a radical operation, sparing accidental damage to the parathyroid glands. Although reported to be useful during surgery, the safety of nano-carbon particles has rarely been investigated, and adverse side effects need to be studied. Case presentation: We describe five patients with thyroid cancer who had carbon secretions in the trachea or mucosa after carbon nanoparticles were injected into the thyroid. A patient with carbon secretions in the trachea mucosa recovered but had progressive dyspnea. Surgical treatment was performed, and a mass was found in the trachea mucosa. After excluding all other possibilities, we concluded that the mass was caused by nano-carbon suspension. Discussion: To our knowledge, there are no reports on nano-carbon suspension into the mucosa and no consensus has yet been reached on the precise injection site, depth, or dose for injecting carbon nanoparticles before thyroidectomy. Conclusion: We suggest that the most appropriate injection depth of nano-carbon suspensions should be no more than 3 mm of the thyroid gland thickness to avoid deep injection into the trachea.

Prognostic factors and nomogram construction for primary retroperitoneal myxoid/round cell liposarcoma: an analysis of population-based data

Background: It has been reported that the prognosis for myxoid/round cell liposarcoma (MLPS/RCLPS) is inconsistent across different sites. However, there are neither prognostic studies nor predictive models that focused on MLPS/RCLPS of retroperitoneal origin. Methods: Utilizing the Surveillance, Epidemiology, and End Results database, we selected 171 primary retroperitoneal MLPS/RCLPS cases from the period between 2000 and 2019. Prognostic factors influencing disease-specific survival were identified through Cox regression analysis. These independent prognostic factors were then used to construct a DSS nomogram prediction model. The accuracy and reliability of this nomogram were evaluated using the concordance index (C-index) and calibration plots. Furthermore, we categorized patient prognosis using an X-tile based on the nomogram score. Results: The observed 5-year and 10-year DSS rates for all patients were 64.0% (95% CI: 56.2% – 71.8%) and 47.1% (95% CI: 38.1% – 56.1%), respectively. The patient cohort had a median age of 64 years, ranging from 24 to 92 years, with a slight male predominance (n = 92, 53.8%) over females (n = 79, 46.2%). Distant metastases were diagnosed in 24 patients (14%). The distribution of MLPS and RCLPS was 89.5% and 10.5%, respectively. In terms of treatment, adjuvant radiotherapy was administered to 33 patients (19.3%), neoadjuvant radiotherapy to 9 patients (5.3%), and chemotherapy to 20 patients (11.7%), while a significant majority (83.6%) underwent surgical procedures. Independent prognostic factors for DSS included age (HR = 1.039, P &lt; 0.001), marital status (P = 0.029), history of previous tumors (HR = 0.257, P = 0.007), presence of metastatic disease (HR = 2.206, P = 0.027), and surgical treatment (HR = 0.490, P = 0.036). A nomogram prediction model was constructed to forecast 1-, 5-, and 10-year DSS rates, with a C-index of 0.739. Calibration plots demonstrated a strong correlation between the nomogram’s predictions and actual observations. Based on the prediction model, patients were stratified into three groups, and significant differences in prognosis were observed between these groups. Conclusion: A poorer prognosis is associated with retroperitoneal-derived MLPS/RCLPS than with other sites. The nomogram prediction model we built can be used to assist patients in consulting with their doctors and selecting patients for clinical trials. Relevance for Patients: Our study highlights the unique challenges and prognosis variations in retroperitoneal myxoid/RCLPS. The developed nomogram serves as a valuable tool for patients, aiding informed discussions with doctors and guiding decisions on treatment and clinical trial participation.

Alliance A022101: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer—Evaluating radiation, ablation, and surgery (ERASur).

TPS236 Background: For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. Methods: A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with ≤4 sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023 and recruitment is ongoing. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org. U10CA180820 (ECOG-ACRIN); U10CA180868 (NRG); U10CA180888 (SWOG). Clinical trial information: NCT05673148 .

CT predictors of sub-centimeter occult lymph node metastases in oral cavity squamous cell carcinoma: A case-control study.

For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance. To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology. Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p = .01), asymmetric number (OR = 7.20, p = .005), and disrupted fatty hilum (OR = 3.31, p = .04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%. In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease.

Primary squamous cell carcinoma of the pancreas: an update on a rare neoplasm from the SEER database.

Pancreatic squamous cell carcinoma is a rare type of pancreatic cancer of ductal origin, composing an estimated 0.5 - 5% of pancreatic ductal malignancies. As a result, epidemiology, treatment options, and associated outcomes are poorly understood and understudied. Our aim was two-fold: to evaluate demographic trends and analyze overall survival (OS) associated with different treatment modalities for this rare malignancy. Patients with pancreatic squamous cell carcinoma diagnosed between 1992 and 2019 were eligible and reviewed utilizing the Surveillance, Epidemiology, and End Results Registry (SEER) database. Data was analyzed using SPSS and python packages lifelines and pandas. Variables of interest included stage at diagnosis as well as the receipt of surgery, radiotherapy, and/or chemotherapy. Five-year OS curves were analyzed using Kaplan-Meier probability stratified by treatment modality. Of 342 cases of pancreatic squamous cell carcinoma, 170 (49.7%) were females and 172 (50.3%) were males. 72 (21.1%) of patients received radiotherapy, 123 (35.9%) patients received chemotherapy, and 47 (13.7%) received surgery. Patients who were diagnosed under the age of 50 had prolonged survival time compared to those diagnosed over the age of 50 (12 vs 8 months, respectively, p < 0.001). This trend was evident despite the lack of a significant association between age at diagnosis and presence of metastases (p = 0.524). The median OS was 3 months for the entire cohort and there was a significant difference in median survival time noted across treatment modalities: OS was prolonged in those receiving surgery compared to those receiving chemotherapy or radiotherapy alone (30 vs 2 months, respectively, (p<0.001)). Receipt of radiotherapy was not associated with a significant difference in OS compared to those who did not receive radiotherapy. Pancreatic squamous cell carcinoma is a rare subtype of pancreatic cancer and typically portends a poor prognosis. As demonstrated by our study, surgery offers prolonged overall survival compared to other treatment modalities. Age at diagnosis and presence of metastatic disease are also important prognostic factors likely related to patients' ability to tolerate surgery or physician willingness to offer surgery. Given the importance of surgery on outcomes, it may be reasonable to offer it in the oligometastatic setting in patients who are otherwise a good candidate. Future research on larger cohorts is warranted to investigate the role that modality selection plays in overall survival rates in this understudied malignancy.

Comparison of Khorana Vs. Onkotev Predictive Score to Individualize Anticoagulant Prophylaxis in Ambulatory Patients with Cancer

Background: The current guidelines [ J Clin Oncol. 2020;38(5):496] recommend using the risk assessment model (RAM) Khorana score ≥2 [ Blood. 2008;111(10):4902-4907] for primary anticoagulant prophylaxis (PP) of venous thromboembolism (VTE) in patients treated for cancer in an outpatient setting. Recently, a novel RAM, the ONKOTEV score [ JAMA Network Open 2023;6(2):e230010] has been prospectively externally validated with good predictive performance. Like all other established RAMs, the Khorana Score and ONKOTEV models aim to assess the incidence of VTE accurately but do not integrate the expected benefits and potential harms of treatment to determine the clinical utility of the competing management alternatives. We set out to compare the clinical utility of the Khorana Score vs. the ONKOTEV predictive model to guide the PP of VTE in patients receiving anticancer treatment. Methods: We used the ONKOTEV validation dataset (n=425). The ONKOTEV score included the Khorana Score (dichotomized as Khorana score &amp;gt;2 vs. ≤ 2) and three readily available clinical information (also dichotomized): history of previous VTE, the presence of metastatic disease, and clinical or radiological assessment of vascular or lymphatic compression by tumor. After assessing the models' performance (discrimination, calibration), we applied a generalized decision curve analysis (gDCA) to integrate the effects of treatments with the models' predictive accuracy. This, in turn, allowed us to develop individualized recommendations for using PP for VTE in patients receiving anticancer treatment. We calculated net benefits (NB) to compare three management strategies: don't provide any treatment vs. administer prophylaxis to all patients receiving anticancer treatment for VTE vs. use the Khorana or ONKOTEV model to guide PP of VTE. According to gDCA, the best treatment is the one with the highest NB. We obtained data on treatment effects from the meta-analysis of published randomized trials comparing direct oral anticoagulants (DOAC) and low-molecular-weight heparins (LMWH) vs. placebo [ Annals of Palliative Medicine. 2020;9(5):2970]. We estimated that DOAC reduced the risk of VTE by 57% [relative risk reduction (RRR) =0.57 (95%CI: 0.13 to 0.79)] and LMWH by 48% [RRR=0.48 (95%CI: 0.42 to 0.66)]. We assessed the major bleeding rate on DOAC as 0.01 (95%CI: 0.006 to 0.04) and 0.02 (95%CI: 0.01 to 0.03) for LMWH. Results: Both RAMs had a satisfactory performance. Harell's C discrimination statistics was 0.71 for ONKOTEV and 0.66 for Khorana Score with good calibration properties (with intercept and the slope not statistically significantly different from 0 and 1, respectively). Fig 1A shows the results based on the default assumptions: if the patient values avoiding the morbidity of VTE 1.6 to 5 times more (0.2&amp;lt;RV&amp;lt;0.6) than the major bleeding, then offering DOAC to all patients receiving PP for VTE represents the most optimal management strategy. When the patients would rather avoid the consequences of the major bleeding by &amp;gt;2.5x more than the morbidity of VTE, using the ONKOTEV model to guide the administration of DOAC represents the best treatment strategy. If we assume that RRR ≤ 0.2, relying on the ONKOTEV model to guide the use of DOAC becomes the most optimal approach to PP of VTE in patients receiving anticancer treatment (Fig 1B). Conclusion: ONKOTEV model is superior to Khorana Score in guiding individualized PP for VTE in ambulatory patients with cancer. It is particularly helpful when the patient values avoiding major bleeding more than the morbidity of VTE. Our analysis provides new recommendations for PP of VTE receiving outpatient treatment for cancer, calling for updating the current guidelines for PP of VTE in this setting.

Correlation Between Oligometastatic Tumor in Two Other Visceral Organs and Prognosis in Patients With Brain Metastases.

Background and Objective: A recent report indicated that metastases to other body organs commonly develop after stereotactic body radiation treatment for cure in patients with oligometastases (OGM) confined to one organ. This study was undertaken to determine if the presence of metastatic disease in two other visceral organs (TVO) in patients with conventionally treated brain metastases (BRM) was associated with poorer prognosis. Methods: This retrospective clinical investigation included 26 patients treated for palliation of OGM-BRM between May 1996 and February 2020. These individuals were classified according to the presence (13 patients) or absence (13 patients) of metastases in TVO. Results: With an overall mean follow-up of 16 months, 20 patients were deceased, and 6 patients were alive. The median survivals for the OGM-BRM-TVO and non-OGM-BRM-TVO subsets were 4 and 12 months, respectively; the corresponding crude survival rates at 12 months were 0% and 46% (p < 0.01). Subgroup analysis correlating prognosis to the number of BRM (single vs. multiple) and OGM-BRM categories (synchronous vs. metachronous) failed to reveal a survival advantage favoring a certain subgroup. Conclusion: Although the evidence is speculative, we believe that an aggressive disease condition is more likely present in patients with OGM-BRM-TVO. With the notion of an overall poor survival, we suggest a more tailored, less or nonharmful management approach (i.e., palliative therapy or hospice) for this particular patient cohort.

Imaging Update for Hereditary Abdominopelvic Neuroendocrine Neoplasms.

Neuroendocrine neoplasms have shown a linear increase in incidence and prevalence in recent decades, primarily due to improved cross-sectional imaging, expanded use of endoscopic procedures, and advanced genetic analysis. However, diagnosis of hereditary neuroendocrine tumors is still challenging because of heterogeneity in their presentation, the variety of tumor locations, and multiple associated syndromes. Radiologists should be familiar with the spectrum of these tumors and associated hereditary syndromes. Furthermore, as the assessment of multiple tumor elements such as morphology, biochemical markers, and presence of metastatic disease are essential for the treatment plan, conventional anatomic and functional imaging methods are fundamental in managing and surveilling these cases. Our article illustrates the role of different cross-sectional imaging modalities in diagnosing and managing various hereditary abdominopelvic neuroendocrine tumors.

Alliance A022101: A Pragmatic Randomized Phase III Trial Evaluating Total Ablative Therapy for Patients with Limited Metastatic Colorectal Cancer – Evaluating Radiation, Ablation and Surgery (ERASur)

For patients with oligometastatic colorectal cancer (CRC), aggressive local therapy of isolated metastases, particularly in the liver, has been associated with long-term progression-free survival and overall survival (OS) primarily based on retrospective evidence. However, in patients with limited metastatic CRC that is deemed inoperable or those with additional disease outside of the liver or lungs, the role of local ablative therapies, including microwave ablation (MWA) and stereotactic body radiation therapy (SBRT), to render patients disease free is less clear. Further, despite the long history of treating oligometastatic CRC with local therapy, which is provider biased and not evidence based, questions remain regarding the benefit of extending the paradigm of metastatic directed therapy to patients with more extensive disease. This trial seeks to use a pragmatic multimodality approach that mirrors the current clinical dilemma. This study is designed to evaluate the safety and efficacy of adding total ablative therapy (TAT) of all sites of disease to standard of care systemic treatment in those with limited metastatic CRC. A022101 is a National Clinical Trials Network randomized phase III study planned to enroll 364 patients with newly diagnosed metastatic CRC (BRAF wild-type, microsatellite stable) with 4 or fewer sites of metastatic disease on baseline imaging. Liver-only metastatic disease is not permitted, and lesions must be amenable to any combination of surgical resection, MWA, and/or SBRT with SBRT required for at least one lesion. Patients receive first-line systemic therapy for 4-6 months and are then randomized 1:1, stratified by number of metastatic organ sites (1-2 vs. 3-4), timing of metastatic disease diagnosis (de novo vs. secondary), and presence of metastatic disease outside the liver and lungs in at least one site. Patients in Arm 1 will receive TAT which consists of treatment of all metastatic sites with SBRT ± MWA ± surgical resection followed by standard of care systemic therapy. Patients in Arm 2 will continue with standard of care systemic therapy alone. The primary endpoint is OS. Secondary endpoints include event-free survival, treatment-related toxicities, and local recurrence with exploratory biomarker analyses. The study needs 346 evaluable patients combined in the 2 arms to demonstrate an improvement in OS with a hazard ratio of 0.7 to provide 80% power with a one-sided alpha of 5%. The trial utilizes a group sequential design with two interim analyses (25% and 50% of events) for futility. The trial activated in January 2023. Recruitment is ongoing.

Benefits of Dual-Layer Spectral CT Imaging in Staging and Preoperative Evaluation of Pancreatic Ductal Adenocarcinoma.

Imaging of pancreatic malignancies is challenging but has a major impact on the patients therapeutic approach and outcome. In particular with pancreatic ductal adenocarcinoma (PDAC), usually a hypovascularized tumor, conventional CT imaging can be prone to errors in determining tumor extent and presence of metastatic disease. Dual-layer spectral detector CT (SDCT) is an emerging technique for acquiring spectral information without the need for prospective patient selection or specific protocols, with a detector capable of differentiating high- and low-energy photons to acquire full spectral images. In this review, we present the diagnostic benefits and capabilities of modern SDCT imaging with a focus on PDAC. We highlight the most useful virtual reconstructions in oncologic imaging and their benefits in staging and assessment of resectability in PDAC, including the assessment of tumor extent, vascular infiltration, and metastatic disease. We present imaging examples on a latest-generation SDCT scanner.

Survival Among Post-Operative Non-Small Cell Lung Cancer Patients Receiving Chemoradiotherapy; A Retrospective Analysis

Background: Despite being the second most frequent malignancy, lung cancer is the main reason for cancer-related fatalities. In this study, patients who underwent surgery for Non-Small Cell Lung Cancer and received adjuvant chemoradiotherapy will be evaluated. Patients and Methods: The data of 123 eligible patients who were operated with the diagnosis of Non-Small Cell Lung Cancer between 2000 and 2020 and who were treated with adjuvant chemoradiotherapy were retrospectively analyzed. Results: Of the 123 patients that were included in the study, 111 (90%) were males and 12 (10%) were females. The mean age was 62.11±8.92 (range:33-77) years. According to histological types, 65 (53%) patients were squamous cell carcinoma, 54 (44%) patients were adenocarcinoma and 4 (3%) patients were large cell carcinoma. Fifty-nine (48%) patients had undergone right lobectomy, 43 (35%) patients left lobectomy, 7 (6%) patients right pneumonectomy and 14 (11%) patients had left pneumonectomy. Mean OS time of all patients was 63.34±5.98 (51.62-75.07) months. One, 2, 3 and 5-year survival rates were 89.9%, 66.9%, 56.3% and 40.9%, respectively. There was a significant correlation between the T stage (p=0.05) of the disease and the chemotherapy protocol (p=0.046) and survival. Conclusion: Complete surgical resection remains the most effective treatment for patients with operable Non-Small Cell Lung Cancer. The high risks of distant recurrence brought on by the presence of metastatic disease that went unnoticed prior to surgery, however, restrict the effectiveness of surgical resection. Therefore, postoperative chemoradiotherapy employing constrained areas and contemporary approaches can be advantageous.

Cancer treatment delays among cancer patients living with HIV during the COVID-19 pandemic in the United States.

The COVID-19 pandemic led to care disruptions across the cancer continuum. It is unknown if immunosuppressed patients with cancer, who may be at higher risk for complications of SARS-CoV-2 infection, are disproportionately impacted. Thus, we aimed to compare delays in cancer treatment initiation between people living with HIV (PLWH) and cancer, the general cancer population (GCP), and patients with cancer and a history of solid organ transplant (SOT). Comparisons were made across the period 2 years preceding the pandemic versus the first year of the pandemic. We used data from a real-world electronic health record-derived de-identified database (2018-2021) comprised of US patients with cancer from 800 sites of care across the country. We included patients with 19 different cancer types. We calculated time to cancer treatment initiation (TTI) as the difference between the date of cancer diagnosis and the earliest date that cancer treatment was recorded. The sample included 181 PLWH, 65,073 GCP patients, and 195 patients with a SOT. Difference-in-difference regression models adjusted for age, sex, and presence of metastatic disease at cancer diagnosis revealed a significant increase in delayed TTI among PLWH compared to the GCP during COVID-19 versus prior to COVID-19, with delays increasing by approximately 1 month during the pandemic (DID: 32.6 days [8.9-56.3]; p = 0.007). The increase in TTI for PLWH was observed across treatment modalities, including surgery (DID: 55.1 [28.8-81.3], p < 0.001) and systemic therapy (DID: 30.4 [4.6-56.3], p = 0.021). PLWH experienced significant delays in cancer treatment initiation after diagnosis during the first year of COVID-19, delays that may negatively impact cancer outcomes. These data warrant patient and provider attention as the pandemic continues to impact the US healthcare system.

Medulloblastoma

In the 5th edition of the WHO classification, medulloblastomas, which are representative pediatric brain tumors, are categorized into four groups: WNT, SHH-TP53 wild, SHH-TP53 mutant, and non-WNT/non-SHH, based on their molecular background. While the histopathological findings still hold importance in predicting prognosis, the histopathological classification is no longer utilized in this edition. SHH medulloblastomas are further subdivided into two groups based on the presence or absence of TP53 mutation, as their clinical characteristics and prognosis differ. Group 3 and Group 4 medulloblastomas, recognized as distinct molecular groups in clinical practice, are combined into a single group called "non-WNT/non-SHH", because they lack specific molecular pathway activation. Furthermore, based on methylation profiling, dividing SHH medulloblastoma into four subgroups and non-WNT/non-SHH medulloblastoma into eight subgroups was proposed. Understanding the unique clinical characteristics and prognosis associated with each group is crucial. However, it is important to acknowledge that our current understanding of prognosis is based on treatment approaches guided by clinical risk factors such as postoperative residual tumor volume and the presence of metastatic disease. This molecular-based classification holds promise in guiding the development of optimal treatment strategies for patients with medulloblastoma.