Non-metastatic Patients Research Articles

Distress Tolerance in Patients with Metastatic and Non-metastatic Breast Cancer: A Single-center Experience

Background: Psychosocial difficulties occur in patients with breast cancer for many reasons including long-term treatments, organ loss, or deformity. Accordingly, we aimed to compare differences in distress tolerance levels between metastatic and non-metastatic female patients diagnosed with breast cancer and receiving chemotherapy. We also evaluated the possible relationship between distress tolerance levels and with background and clinical characteristics of the patients. 
 
 Methods: 208 eligible female patients with breast cancer who received at least three chemotherapy sessions were included in our study. According to the presence of metastasis, the patients were divided into two groups those receiving palliative (metastatic, n=126) and adjuvant (non-metastatic, n=82) chemotherapy. Besides the study-specific data form, the Distress Tolerance Scale (DTS) was applied to patients to assess distress tolerance levels.
 
 Results: The age of participants was statistically significant between the non-metastatic and metastatic patients(p

Transglutaminase 2 expression is associated with increased risk of lymph node metastasis and recurrence in papillary thyroid cancer.

Transglutaminase 2 (TG2) is associated with mobilization, invasion, and chemoresistance of tumor cells. We aimed to determine whether the immunohistochemical staining with TG2 antibody differs between metastatic and non-metastatic papillary thyroid cancer patients. We included 76 patients with papillary thyroid cancer (72% female, median age 52 (24-81) years, follow-up time 107 (60-216) months). Thirty of them with no metastasis, 30 of them with only lymph node metastasis and 16 patients with distant ± lymph node metastasis. Immunohistochemical staining of TG2 antibody was evaluated in the primary tumor and extra-tumoral tissue. We also divided subjects into two groups according to their primary tumor TG2 staining score (group A, high risk group: ≥3, n = 43; group B, low risk group: <3, n = 33). Vascular invasion (p < 0.001), thyroid capsule invasion (p < 0.001), extrathyroidal extension (p < 0.001), intrathyroidal dissemination (p = 0.001), lymph node metastasis (p < 0.001), presence of aggressive histology (p < 0.001) were significantly higher in group A. No significant difference was found between the groups in terms of distant metastasis. Based on ATA risk classification 95.5% of patients with low risk were in group B but 86.8% of intermediate risk and 56.3% of high risk were in group A. In regression analysis, lymph node metastasis increased by 1.9 times with each one point increase in TG2 staining score. TG2 staining score of the primary tumor may be a predictive factor for lymph node metastasis. High or low TG2 scores may effect the frequency of follow-up and decision of treatment regimens.

Association of Paclitaxel Induced Neuropathy with Quality of Life of Patients with Non-Metastatic Breast Cancer

Objective: To look for an association of Paclitaxel induced neuropathy with the quality of Life of patients with non-metastatic breast cancer.&#x0D; Study Design: Comparative cross-sectional study.&#x0D; Place and Duration of Study: Oncology Department, Combined Military Hospital, Rawalpindi Pakistan, from Nov 2021 to Feb 2022.&#x0D; Methodology: The study included one hundred and twenty patients with diagnosed non-metastatic breast cancer taking Paclitaxel chemotherapy for more than one month. Peripheral neurotoxicity was assessed by a consultant oncologist based on the Eastern Cooperative Oncology Group (ECOG) score. In addition, quality of Life was recorded with the help of the World Health Organization Quality of Life (WHOQOL)-BREF scale in all the study participants and associated with the presence and severity of neuropathy.&#x0D; Results: Out of 120 non-metastatic breast cancer patients using Paclitaxel for more than one month included in the study, 113 (94.2%) were female, while 7(5.8%) were male. 52(48.3%) had good quality of Life, while 68(51.7%) had poor quality of Life. 34(28.3%) had Grade-0 neuropathy, 54 (45%) had Grade-I, 30(25%) had Grade-II, and 2(1.6%) had Grade-III neuropathy.Statistical analysis showed that the presence and severity of neurotoxicity had a statistically significant relationship with poor quality of Life (p-value=0.001).&#x0D; Conclusion: Many patients having breast cancer using Paclitaxel had the presence of neuropathy. The presence and severity of neuropathy are strongly associated with poor quality of Life in patients included in our study.Keywords: Breast cancer, Neurotoxicity, Paclitaxel, Quality of life.

The Impact of NUTRItional Status at First Medical Oncology Visit on Clinical Outcomes: The NUTRIONCO Study.

Malnutrition affects up to 75% of cancer patients and results from a combination of anorexia and metabolic dysregulation. Metabolic and nutritional abnormalities in cancer patients can lead to cachexia, a multifactorial syndrome characterized by involuntary loss of skeletal muscle mass, systemic inflammation and increased protein catabolism. Cancer cachexia negatively affects patients' outcomes, response to anticancer treatments, quality of life, and survival. However, risk of malnutrition, and cachexia are still under-recognized in cancer patients. The Prevalence of Malnutrition in Oncology (PreMiO) study revealed that 51% of patients already had nutritional deficiencies at their first medical oncology visit. Here, we report the results of the subsequent retrospective, observational NUTRItional status at first medical oncology visit ON Clinical Outcomes (NUTRIONCO) study, aimed at assessing the impact of baseline nutritional and non-nutritional variables collected in the PreMiO study on the clinical outcomes of the same patients followed up from August 2019 to October 2021. We have highlighted a statistically significant association between baseline variables and patient death, rehospitalization, treatment toxicity, and disease progression at follow-up. We found a higher overall survival probability in the well-nourished general study population vs. malnourished patients (p < 0.001). Of major interest is the fact that patient stratification revealed that malnutrition decreased survival probability in non-metastatic patients but not in metastatic patients (p < 0.001). Multivariate analysis confirmed that baseline malnutrition (p = 0.004) and VAS score for appetite loss (p = 0.0104), in addition to albumin < 35 g/L (p < 0.0001) and neutrophil/lymphocyte ratio > 3 (p = 0.0007), were independently associated with the death of non-metastatic patients at follow-up. These findings highlight the importance of proactive, early management of malnutrition and cachexia in cancer patients, and in particular, in non-metastatic patients, from the perspective of a substantial improvement of their clinical outcomes.

Targeting the KRT16-vimentin axis for metastasis in lung cancer

Lung cancer is the most diagnosed malignant cancer and the leading cause of cancer-related deaths worldwide, with advanced stage and metastasis being a major issue. The mechanism leading to metastasis is not yet understood. Here, we found that KRT16 is upregulated in metastatic lung cancer tissues and correlated with poor overall survival. Knockdown of KRT16 inhibits metastasis of lung cancer both in vitro and in vivo. Mechanistically, KRT16 interacts with vimentin, and depletion of KRT16 leads to downregulation of vimentin. KRT16 acquired its oncogenic ability by stabilizing vimentin, and vimentin is required for KRT16-driven metastasis. FBXO21 mediates the polyubiquitination and degradation of KRT16, and vimentin inhibits KRT16 ubiquitination and degradation by impairing its interaction with FBXO21. Significantly, IL-15 inhibits metastasis of lung cancer in a mouse model through upregulation of FBXO21, and the level of IL-15 in circulating serum was significantly higher in nonmetastatic lung cancer patients than in metastatic patients. Our findings indicate that targeting the FBXO21/KRT16/vimentin axis may benefit lung cancer patients with metastasis.

Evaluation of Three-Year Overall and Disease-Free Survival in Iranian Patients with Nasopharyngeal Carcinoma Treated by Intensity-Modulated Radiotherapy (IMRT): A Historical Cohort Single Center Study

Background: The aim of this study was to evaluate and analyze disease-free survival (DFS) and overall survival (OS) after intensity-modulated radiotherapy (IMRT) for Iranian patients with nasopharyngeal carcinoma (NC). Methods: In this historical cohort study, 65 non-metastatic patients treated for NC with IMRT were selected and reviewed at the Shohadai-e-Tajrish Hospital between October 2017 and October 2019. Chemotherapy was given either as induction, concurrent, or adjuvant therapy in all cases. Three years of DFS and OS were calculated according to Kaplan-Meier and compared with the Pearson Correlation Test. Results: The mean age of patients was 43.38 years. The three-year DFS and OS rates were 95.72%, 92.32%, 72.73%, 73.26%, and 100%, 84.61%, 90.90%, and 79.41% in stage I, II, III, and IV patients, respectively (P = 0.119, P = 0.155). The total three-year DFS rate and the total three-year OS rate were 76.47% and 84.60% in all cases. Based on the Pearson Correlation Test, it was a significant correlation between the duration of IMRT time and three-year DFS (correlation=0.138, P = 0.017) and the number of concurrent cycles of chemotherapy with IMRT (correlation=0.375, P = 0.002). It was not a significant correlation between total time duration, MRI response, induction chemotherapy, age, sex, and the three-year DFS. There was a significant correlation between total time duration and three-year OS (correlation=0.263, P = 0.040) and the number of concurrent cycles of chemotherapy with IMRT and three-year OS (correlation=0.334, P = 0.007). It was not a significant correlation between the duration of IMRT time, MRI response, induction chemotherapy, age, sex, and the three-year OS. Conclusions: Our findings showed that IMRT with concurrent chemo-radiotherapy has the three-year DFS and OS, which were comparable with the other published results. We emphasize the number of concurrent cycles of chemotherapy with IMRT, which have an important role in both three-year DFS and OS. The duration of IMRT time has also an important role in the three-year DFS but not in the three-year OS. A longer follow-up for the patients to evaluate 10-year DFS and OS is recommended.

Impairment in Activities of Daily Living Assessed by the Barthel Index Predicts Adverse Oncological Outcomes After Radical Cystectomy for Bladder Cancer

IntroductionWe tested the association between functional impairment in activities of daily living (ADL) assessed through the Barthel Index (BI), and oncological outcomes following radical cystectomy (RC) for bladder cancer (BCa). Patients and MethodsWe retrospectively analyzed data of 262 clinically nonmetastatic BCa patients, who underwent RC between 2015 and 2022, with available follow-up. According to preoperative BI, patients were divided in 2 groups: BI ≤90 (moderate/severe/total dependency in ADL) versus BI 95 to 100 (slight dependency/independency in ADL). Kaplan-Meier plots compared disease recurrence (DR)-, cancer-specific mortality (CSM)-, and overall mortality (OM)-free survival according to established categories. Multivariable Cox regression models tested the BI as an independent predictor of oncological outcomes. ResultsAccording to the BI, the patient cohort was distributed as follows: 19% (n = 50) BI ≤90 versus 81% (n = 212) BI 95-100. Compared to patients with BI 95 to 100, patients with BI ≤90 were less likely to receive intravesical immuno- or chemotherapy (18% vs. 34%, p = .028), and more frequently underwent less complex urinary diversion as ureterocutaneostomy (36% vs. 9%, p < .001), or harbored muscle-invasive BCa at final pathology (72% vs. 56%, p = .043). In multivariable Cox regression models adjusted for age, ASA physical status score, pathological T and N stage, and surgical margins status, BI ≤90 independently predicted higher DR (HR [hazard ratio]:2.00, 95%CI [confidence interval]:1.21-3.30, p = .007), CSM (HR:2.70, 95%CI:1.48-4.90, p = .001), and OM (HR:2.09, 95%CI:1.28-3.43, p = .003). ConclusionPreoperative impairment in ADL was associated with adverse oncological outcomes following RC for BCa. The integration of the BI into clinical practice may improve the risk assessment of BCa patients candidates to RC.

Conditional survival nomogram for monitoring real-time survival of young non-metastatic nasopharyngeal cancer survivors.

The aim of this study was to clarify the improvement of the overall survival (OS) over time in young non-metastatic nasopharyngeal carcinoma (NPC) survivors by conditional survival (CS) analysis and to construct a CS-nomogram for updating individualized real-time prognosis. The study included 3409 young non-metastatic NPC patients from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2019). OS was estimated using the Kaplan-Meier method. CS was calculated based on CS(y|x) = OS(y + x)/OS(x), defined as the probability that a patient would survive for another y years after surviving for x years since diagnosis. We identified predictors using the least absolute shrinkage and selection operator (LASSO) regression and developed the CS-nomogram using multivariate Cox regression and the CS formula. CS analysis showed a continuous increase in 10-year OS for young non-metastatic NPC from the initial 60.4% to 65.0%, 70.2%, 74.2%, 78.2%, 82.6%, 86.9%, 91.1%, 96.2% and 97.0% (surviving 1-9years after diagnosis, respectively). After screening by LASSO regression, age, race, marital status, histological type, T- and N-status were used as predictors to construct the CS-nomogram. The model accurately estimated the real-time prognosis of survivors during follow-up with a stable time-dependent area under the curve (AUC). CS analysis based on SEER database calibrated the real-time prognosis of young non-metastatic NPC survivors, revealing a dynamic improvement during follow-up time. We developed a novel CS-nomogram to update survival data for real-time optimization of monitoring strategies, medical resource allocation, and patient counseling. However, it was important to note that the model still needed external data validation and continuous improvement.

Abstract A046: Integrated genomic analysis of primary prostate tumor foci and corresponding lymph node metastases identifies pathways associated with metastatic disease

Abstract Background: Prostate cancer (PCa) is a highly heterogeneous disease, and mortality is mainly due to metastases. However, the molecular underpinnings that lead to the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM). Design: Primary tumor foci (PTF) and LNM from 40 patients with high-risk PCa were analyzed by RNAseq. Two or more PTF and all available LNM greater than 0.4cm were subjected to sequencing. Of these 40 patients, 17 (42.5%) had LNM and 23 (57.5%) had benign LNs. A total of 155 tissue samples (97 PTF, 39 benign LNs, and 19 LNM) were sequenced and mapped to the human transcriptome with STAR mapper after QC trimming and removal of adapter sequences using TrimGalore. Differentially expressed genes between PTF, LNM, and benign LNs were identified using DESeq2, and gene set enrichment analysis was performed using WebGestalt. WES data was analyzed using GATK pipelines including Mutect2 and maftools. Results: A median of 57 million paired-end reads were obtained per sample, with a median of 10 million total readcounts per sample across the transcriptome, and 39,021 transcripts were detected in at least 5% of samples. Comparing PTF to LNM, 6203 transcripts were differentially expressed (p-adj &amp;lt; 0.01). PTF were enriched relative to LNM in gene sets associated with Wnt signaling, hormone signaling, Hippo signaling, KRAS signaling, and the epithelial to mesenchymal transition. Comparing PTF from metastatic patients to non-metastatic patients, 1265 transcripts were differentially expressed (p-adj &amp;lt; 0.01). PTF from metastatic patients were enriched in gene sets associated with cell cycle progression, oxidative phosphorylation, ER stress, fatty acid metabolism, and DNA repair. LNM gene sets were enriched in endoplasmic reticulum (ER) stress and oxidative phosphorylation. The top 500 upregulated genes in malignant tissues were significantly enriched in genes related to androgen and estrogen signaling as expected. We also identified a set of 193 genes whose expression was significantly increased in primary tumor over benign LNs and in LNM over primary tumors. This gene set was significantly enriched in genes related to oxidative phosphorylation and included oncogenes such as PIK3CB, NCOA2, and SCHLAP1. Frequently mutated genes included CSMD3, FAT4, DNAH7, and KMT2C. DNA mutations associated with metastases included PCNX2. Oncogenic pathways associated with metastases in WES analysis included RAS, Notch, Wnt, Hippo, and PI3K pathways. Conclusions: Signaling pathways associated with ER stress, oxidative phosphorylation, metabolism, and cell cycle progression are prominent in LNM of aggressive PCa. PIK3CB, NCOA2, and SCHLAP1 expression are significantly increased in LNM. LNM had higher mutational burdens and were associated with hypermutability pathways, as well as mutations in RAS, Notch, Wnt, Hippo, and PI3K pathway genes. Citation Format: Carlos S. Moreno, Cynthia L. Winham, Emma R. Klein, Yijian Huang, David M. Schuster, Martin G. Sanda, Adeboye O. Osunkoya. Integrated genomic analysis of primary prostate tumor foci and corresponding lymph node metastases identifies pathways associated with metastatic disease [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr A046.

The impact of treatment adherence on overall survival in non-metastatic colorectal cancer in Latin American patients.

e15644 Background: Colorectal cancer is a significant public health issue in Peru, and non-metastatic colorectal cancer patients face numerous treatment challenges. Adherence to treatment protocols has been identified as an important factor influencing patient outcomes. However, little is known about the impact of treatment adherence on overall survival in non-metastatic colorectal cancer patients in Peru. The objective of this study is to investigate the association between treatment adherence and overall survival in this patient population. Methods: We retrospectively reviewed the electronic medical files of 890 patients with non metastatic colorectal cancer between 2006 and 2020. Patients were included if they received treatment and were followed up for at least two years. Treatment adherence was measured based on the number of completed chemotherapy cycles and the time to initiate treatment after surgery. Overall survival was defined as the time from diagnosis to death or the last follow-up visit. Multivariate analysis was performed to identify factors associated with overall survival. Results: A total of 890 patients were included in the study, and the median follow-up time was 32 months. The overall adherence rate was 71.7%. Patients who adhered to treatment had a significantly higher overall survival rate compared to non-adherent patients (p &lt; 0.001). A multivariate analysis was performed using Cox regression model with the statistically significant variables found (sex, high histologic grade, stage and adherence to treatment) in the univariate analysis. Multivariate analysis showed that treatment adherence was an independent predictor of overall survival (HR = 0.69; 95% CI, 0.54-0.88; p &lt; 0.001). Conclusions: Our findings indicate that medication adherence is a crucial factor affecting overall survival in Peruvian patients with non-metastatic colorectal cancer. Patients who adhered to treatment had a significantly higher overall survival rate than non-adherent patients, highlighting the importance of adherence in optimizing patient outcomes. These findings have important clinical implications for healthcare providers, who should prioritize efforts to improve treatment adherence in this patient population.

Initial chemotherapy for locally advanced and metastatic NUT carcinoma: A report from the NUT carcinoma registry.

9048 Background: NUT carcinoma (NC) is an uncommon squamous cell cancer. This disease is driven by a NUTM1 gene fusion, most commonly encoding a BRD4-NUT fusion oncoprotein, that enhances transcription of numerous genes including MYC. BET bromodomain inhibitors (BBDi), which block oncoprotein binding, are being studied in clinical trials. A subset of NC is sensitive to chemotherapy, but the optimal regimen is unknown; experts have recommended platinum- (PLAT) and ifosfamide-based (IFOS) therapy based on case reports. Methods: Patients with NC with known chemotherapy treatment and survival outcomes who consented to participate in a worldwide registry were included. Cohorts of patients with non-metastatic and metastatic disease were of interest. Medical records were manually reviewed. Results were summarized using 95% confidence intervals (95CI) and Kaplan Meier survival estimates, when appropriate. Results: A total of 60 patients with NC were included and received either PLAT (83%) or IFOS (17%); 38% were female and the median age was 37 (range 10-82); 55% of tumors were thoracic primaries, 48% had squamous differentiation, and 70% were driven by BRD4-NUTM1 (n = 43 with known fusion status). Of 31 patients with non-metastatic disease, 32% had a thoracic primary; 23% received peri-operative chemotherapy and 77% received concurrent chemoradiation (cRT). The most common chemotherapies used for cRT were cisplatin (n = 12), platinum-taxane (n = 6), and platinum-etoposide (n = 5). Of 4 non-metastatic patients who received IFOS, 4 (100%) had a disease-free survival (DFS) &gt; 3 months and 1 (25%) had a DFS &gt; 1 year. By comparison, of the 27 patients who received PLAT, the estimated 3-month and 1-year DFS was 70% (95CI 48-84%) and 53% (95CI 30-71%) respectively. Of the 29 patients with metastatic disease, 79% had a thoracic primary; 6 received IFOS and 23 received PLAT. The most common chemotherapies were platinum-taxane (52%), platinum-etoposide (17%), and ifosfamide-etoposide (14%). ORR of IFOS vs PLAT was 50% (95CI 12-88%) vs 23% (95CI 7-44%). Compared to IFOS, PLAT had similar 3-month and 6-month PFS (3;6mo: PLAT est: 36% [95CI 18-56%]; 9% [95CI 2-25%] vs IFOS 50%; 17%). The estimated 1-year OS and 1-year OS were 18% (95CI 6-35%) vs 33% for PLAT vs IFOS respectively. Of the 5 patients (8%) with a known OS &gt; 3 years, all had a non-thoracic primary, non-metastatic disease, and had received PLAT. Conclusions: NUT carcinoma is a highly aggressive disease. There may be a numerically higher ORR for ifosfamide-based therapy as compared to platinum-based therapy, with limited durability. Development of effective combination targeted therapies, eg. combinations with BBDis, is an urgent unmet need for this patient population.

Racial and ethnic disparities in employment of patients and caregivers following breast cancer diagnosis.

6543 Background: Breast cancer (BC) can negatively impact employment, risking healthcare benefits, financial security and quality of life, especially for underserved minority populations. To better understand the impact of BC diagnosis and treatment on employment, Breastcancer.org conducted an online survey. Methods: Between 6/7-7/12/2022, Breastcancer.org community members were recruited to participate in an anonymous survey in English or Spanish via email, social media, or website ads. Eligible participants were US residents, age ≥18, and diagnosed with BC within the past 10 years. Consented participants answered questions on socio-demographics, financial toxicity, and employment status. Results: Of 2,420 screened, 1,710 met eligibility, and 1,437 participated (84% participation rate). Mean age and time since diagnosis was 46 and 2 years, respectively; 75% were in active treatment for non-metastatic (89%) or metastatic (11%) BC. Patients identified as 60% White (n=868), 26.7% Hispanic (n=384), 8% Black (n=121), or 4% Other (n=64). 94% were women. BC negatively impacted employment for 92% of patients. Full-time employment went from 62% at diagnosis to 40% by the time of the survey. This was more pronounced in metastatic (56% to 25%) vs non-metastatic (63% to 42%) patients (p=0.015). 64% attributed employment changes to their diagnosis, noting reduced hours/income (40%), job change (26%), disability (13%), permanent job loss (13%), and/or early retirement (12%). 36% noted changes in their caregiver’s employment status as well with 30% of caregivers having reduced hours/income, 30% taking time off work, and 27% changing jobs; 9% of caregivers had permanent job loss and 10% retired early. Hispanic patients were younger (p&lt;0.001) and more likely to have young children (p&lt;0.001) and take unpaid leave (p=0.02). (Table). BC diagnosis was also more likely to impact their caregiver’s employment (58%, vs White 25% or Black 41% patients, p&lt;0.001). Conclusions: Breast cancer can cause significant, lasting negative effects on employment status for patients and caregivers that can decrease financial security of the entire family unit. Hispanic patients and individuals with metastatic disease appear to be at highest risk. Legislative protections and financial support may be required to mitigate the significant financial toxicity of a cancer diagnosis, especially for the most vulnerable. [Table: see text]

PSMA PET findings in an “EMBARK-like” cohort of patients with high-risk non-metastatic hormone-sensitive prostate cancer: A single center post-hoc retrospective analysis.

5091 Background: The EMBARK trial is a phase 3, randomized, study evaluating use of enzalutamide with or without concomitant leuprolide in non-metastatic castrate sensitive prostate cancer patients. Eligibility status for the trial relied upon conventional imaging which under detects metastatic disease in comparison to PSMA-PET imaging. The aim of this post-hoc retrospective analysis was to describe the PSMA-PET findings in a patient population representative of the EMBARK trial. Methods: This was a post-hoc, retrospective analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP, RT or SRT. Patients were included if they met eligibility for enrollment in the EMBARK trial at the time of their PSMA scan defined as the following: Rising PSA at a level above 1.0ng/mL (post RP and SRT) or 2.0ng/mL &gt; nadir (post-RT), PSA doubling time ≤ 9 months, Serum testosterone ≥ 150 ng/dL. Exclusion criteria constituted: distant metastatic disease as assessed by radiographic imaging, prior hormonal therapy or systemic therapy for prostate cancer. PSMA PET findings (PROMISE miTNM stage, number of lesions) were collected from the clinical imaging reports. Descriptive statistics were used (median, range). Results: From 2002 patients screened, 146 patients were included in the analysis. Median time from primary therapy to PSMA PET was 39 (2.1-261) months. Median pre-scan PSA levels and PSA doubling time in patients who underwent RP (n=85), dRT (n=22), post-RP SRT (n=39) and overall (n=146) were 2.4 ng/mL (1-72.1), 8.3 ng/mL (2.37-202), 2.58 ng/ml (1.1-32.3), 2.7 ng/mL (1-202), and 3.5 months (1-9), 3.3 months (1-9), 4.4 months (1-9), 3.7 (1-9) months, respectively. PSMA-PET was positive in 80%, 41%, 85%, 83% of the RP, dRT, RP + SRT and overall populations, respectively. Poly-metastatic disease (≥5 lesions) was found in 19%, 32%, 21% and 21% of cases, respectively. PSMA-PET detected disease only localized to the prostate fossa (miT+N0M0) in 7%, 32%, 0% and 9% respectively. PSMA-PET detected pelvic nodal disease (miTxN1M0) in 40% 18% 28% and 34% respectively. PSMA PET detected any distant metastatic disease (miTxNxM1) in 33%, 41% 56% and 40% respectively. PSMA-PET detected metastatic nodal only disease (N1 and/or M1a) in 58% 32% 74% and 39% and osseous disease (M1b) in 19% 23% 31% and 23% cases respectively. Conclusions: In this “EMBARK-like” cohort of patients with high-risk nmCS PCa and PSA DT &lt; 9 months, PSMA PET was positive in 83% of patients, detected M1 disease in 40% of patients and over one-fifth of cases presented with 5 or more lesions. PSMA-PET provides novel additional risk stratification for patients with high-risk nmCS PCa without distant metastasis based on conventional imaging. Further studies are needed to assess its independent prognostic value and use for treatment guidance. Clinical trial information: NCT03582774 .

Trends in utilization of first-line palliative care in non-metastatic hepatocellular carcinoma.

e16234 Background: Palliative care therapies are known to improve the quality of life and even the survival of some patients. Although non-metastatic (stages I-III) hepatocellular carcinoma (HCC) patients often present with significant symptoms, first-line palliative care treatment is uncommon in this setting. Here we characterized rates of palliative care utilization among non-metastatic HCC patients and determined factors associated with palliative care receipt. Methods: We conducted a retrospective review of adult National Cancer Database patients diagnosed with metastatic HCC between 2004 and 2019. We used descriptive analysis for determining palliative care utilization, including palliative chemotherapy, surgery, radiotherapy, and pain management. We performed multivariable logistic regression analysis to assess the association of characteristics with palliative treatment utilization. Results: Among 121,151 patients diagnosed with stage I-III HCC, the utilization of first-line palliative care subsets was only a small portion of 3966 (3.3%). The most commonly used palliative care treatment was pain management (37.4%), followed by systemic chemotherapy (31.1%), radiotherapy (13%), surgery (9.9%), and combination therapies (8.6%). The higher stage, high comorbidity score, and decreased life expectancy were more likely to be associated with received PC. Stage 2 and 3 diseases were associated with increased odds of PC receipt compared to stage 1 disease (odds ratio [OR] = 1.63 [1.45-1.83] and OR = 3.57 [3.22-3.95]; respectively). Comorbidity score 3 was significantly more likely to receive PC than comorbidity score 0 (OR = 1.54 [1.41–1.69]). In addition, life expectancy &gt;24 months was significantly less associated with PC receipt compared to life expectancy &lt; 6 months (OR: 0.23 [0.20-0.26]). Conclusions: First-line palliative care subsets are underutilized to control symptoms among patients with non-metastatic HCC. Targeted efforts should be focused on increasing palliative care delivery in this group which has a vast potential to benefit.

Baseline endogenous serum testosterone levels and all-cause mortality in men with prostate cancer treated by radical radiotherapy: 11-year follow-up data.

e17003 Background: Low levels of serum testosterone are associated with higher all-cause mortality and cardiovascular mortality in some studies.(PMID: 18040028). But men with low levels of serum testosterone at reduced risk of developing prostate cancer. (PMID: 30077399). In middle-aged and elderly men, single point testosterone measurements have been shown to reliably reflect long term androgen exposure. [PMID: 1548361]. We assessed the interaction of pre-treatment serum testosterone levels and long term all-cause mortality in men with newly diagnosed prostate cancer. Methods: Prostate cancer pts enrolled in an ethics approved, prospective study evaluating a rating scale. Baseline serum testosterone levels were measured before the pts were commenced on androgen deprivation therapy and radical radiotherapy. Patient characteristics: Mean age 68.2yrs (median 69yrs); Age range category &lt; 60yrs:14.9% , 61-70yrs:47.3% and &gt; 71 yrs: 37.8%. Charlson Comorbidity Index (CCI) prevalence at baseline as follows CCI- Low risk : 39.9%; CCI-medium risk : 51.4%; CCI-high risk: 8.8%. PSA median level was 10.85 ug/L. Tumour was localised in a majority of pts- stage T1/T2 in 72% . Pts with M1 disease were not enrolled. Histology grade: Gleeson grade 6 in 7.4% and Gleeson grade 7 in 53.4% . Serum testosterone: Median 11.9 nmol/l; Mean 12.4 (Min-Max 2.6 to 26.7). Cox proportional hazards regression used to analyze the effect of baseline Serum Testosterone on long term overall survival, while controlling for covariates (age, cancer T stage, PSA category, Gleeson Category and Charlson Comorbidity index). Results: Lower levels of serum testosterone at baseline were associated with decreased all-cause mortality. There was no significant correlation between testosterone levels and age in our study sample of relatively elderly population (Pearson Correlation p = 0.362); There was no correlation testosterone levels and PSA levels(P = 0.821); no association between serum Testosterone levels and Gleeson Grade as well as T stage. (F = 0.78 ; P = 0.46 and F = 1.34 ; P = 0.26 respectively). There was also no significant variation in testosterone levels according to Comorbidity categorised by Charlson Comorbidity Index. (F = 1.31 P = 0 .26). Conclusions: Lower Serum testosterone levels were associated with decreased all-cause mortality in this prospectively collected survival data of non-metastatic Prostate cancer patients. [Table: see text]

Pharmacological cardioprotective strategy for non-metastatic patients affected by breast cancer receiving an anthracycline-based chemotherapy: Final results of the phase 3 SAFE trial.

12079 Background: Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue. We aim to determine whether pharmacological cardiac prevention could reduce subclinical heart damage in breast cancer (BC) patients treated with anthracycline-based chemotherapy. Methods: The SAFE trial is a four-arm, randomised, phase 3, double-blind, placebo-controlled study. Patients were eligible for trial inclusion if they had indication to primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with prior diagnosis of cardiovascular disease were excluded. Cardioprotective therapy (bisoprolol (B), ramipril (R), or both drugs (B+R), as compared to placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of HER2 positive patients. Doses for all groups were systematically up-titrated, up to the daily target dose of B (5 mg, once daily), R (5 mg, once daily), and placebo, if tolerated. The primary endpoint was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Results: 262 women (median 48 years; range24-75 years) were enrolled and treated in the study. We analysed patients who had completed the pre-planned cardiological assessment at 24 months. All patients received an anthracycline-based chemotherapy, 215 patients received at least 3 cycles of anthracyclines (range 1-6) and 128 patients had postoperative radiation therapy. At Univariate logistic analysis to evaluate the risk of GLS worsening &gt; 10% at 24 months, Odds ratios (OR) for improvement were 0.055, 0.083 and 0.060 for B, R and B+R, respectively (P &lt; 0.0001), if compared to placebo arm. At Univariate logistic analysis to evaluate the risk of 3DLVEF worsening &gt; 10% at 24 months, OR for improvement were 0.019, 0.048 and 0.054 for B, R and B+R, respectively (P &lt; 0.0001), if compared to placebo arm. Study drugs were well tolerated with no serious adverse events, the ramipril plus bisoprolol arm showed significantly more toxic effects and had a significantly higher rate of allocated treatment discontinuation as compared to the other arms. Conclusions: Cardioprotective pharmacological strategies in patients affected by BC receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodelling. Clinical trial information: NCT2236806 .

Clinical and radiological criteria for candidate patients with small bowel neuroendocrine neoplasms (SB-NEN) for minimally invasive surgery: A single-centre experience.

e16246 Background: Although open resection represents the standard of care of localized small bowel neuroendocrine neoplasms (SB-NEN), minimally invasive surgery (MIS) has proven to be a viable alternative in patients with low disease burden. This study aims to assess the reliability of preoperative clinical and radiological criteria used at European Institute of Oncology (IEO) to candidate patients with SI-NEN to MIS. Methods: Patients diagnosed with SB-NEN and eligible for MIS at IEO were retrospectively evaluated between 2013 and 2022. Preoperative physical examination, CT enterography (CTE) and Ga68-DOTATOC-PET-CT were used for clinical staging. At IEO NEN multidisciplinary tumor board, the following eligibility criteria were adopted to candidate patients to MIS (curative or palliative): number and localization of primary tumor, grade of superior mesentery artery and vein encasement by lymph-node metastases of 0-2 according IEO criteria (based on Lardiere-Degalte classification). Information on morphology and carcinoid syndrome were collected. The primary endpoint was laparotomy conversion rate. Results: Twelve patients were selected. Patients’ characteristics are available. Median age at surgery was 55 years (range: 33–73). Among these patients, based on pathological findings, 8 (67%) had confirmed nodal involvement, 3 (25%) metastatic disease and 4 (33%) multifocal primary tumor. Vascular involvement (based on IEO criteria) was found in 9 patients (75%). Of note, only 3 (25%) patients had a functioning tumor as a preoperative finding and all tumors resulted well-differentiated. Among 12 patients which underwent laparoscopic surgery, none has been converted to laparotomy surgery. After a median follow-up of 25.3 months (range: 2.5-71.3), the 1-year disease free survival for non-metastatic patients was of 100%. Conclusions: the assessment of tumor burden with 68Ga-PET-CT and CTE according to IEO criteria could be a reliable method to candidate patients affected by SB-NEN to MIS, according to a multidisciplinary approach.[Table: see text]

Oncologic safety of breast conservation following NACT in women with locally advanced breast cancer.

Breast conservation surgery (BCS) is the accepted standard of treatment for early breast cancer, with evidence from randomized controlled and population-based studies. The oncological outcome of BCS in locally advanced breast cancer (LABC) is mainly available from retrospective series with a small sample size and a shorter follow-up duration. A retrospective observational study of 411 non-metastatic LABC patients who received neoadjuvant chemotherapy (NACT) followed by surgery from 2011 to 2016. We retrieved the data from a prospectively maintained database and electronic medical records. Survival data were analyzed by Kaplan-Meier curves and Cox regression using Statistical Package for the Social Sciences 25 and STATA 14. 146/411 (35.5%) women had BCS with a margin positivity rate of 3.42%. With a median follow-up of 64 months (IQR 61, 66), the local relapse rate was 8.9% in BCS and 8.3% after mastectomy. The estimated 5-year locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS), distant disease-free survival (DDFS) and overall survival (OS) rates of BCS were 86.9%, 63.9%, 71% and 79.3%, and 90.1%, 57.9%, 58.3% and 71.5% in the mastectomy group. On univariate analysis, BCS showed superior survival outcomes compared to mastectomy (unadjusted HR (95% CI) for RFS: 0.70 (0.50-1), DDFS: 0.57 (0.39-0.84), OS: 0.58 (0.36-0.93)). After adjusting for age, cT stage, cN stage, poorer chemotherapy response (ypT0/is, N0) and radiotherapy, BCS and mastectomy groups were found comparable in terms of LRFS (HR: 1.1, 0.53-2.3), DDFS (HR: 0.67, 0.45-1.01), RFS (HR: 0.80, 0.55-1.17) and OS (HR: 0.69, 0.41-1.14). BCS is technically feasible in LABC patients. LABC patients who respond well to NACT can be offered BCS without compromising survival outcomes.

Changing patterns of care for pancreas cancer in Victoria: the 2022 Pancreas Tumour Summit.

The Victorian Government convened the second Pancreas Cancer Summit in 2021 to identify unwarranted variation in care 2016-2019, and to assess trends compared with the first Summit 2017 (reporting 2011-2015). State-wide administrative data were assessed at population level in alignment with optimal care pathways across all stages of the cancer care continuum. Data linkage performed by Centre for Victorian Data Linkage combined data from Victorian Cancer Registry with other administrative data sets including Victorian Admitted Episodes Dataset, Victorian Radiotherapy Minimum Data Set, Victorian Emergency Minimum Dataset and Victorian Death Index. A Cancer Service Performance Indicator audit was carried out providing an in-depth analysis of identified areas of interest. Of 3138 Victorians diagnosed with pancreas ductal adenocarcinoma 2016-2019, 63% were metastatic at diagnosis. One-year survival increased between time periods, from 29.7% overall 2011-2015 (59.1% for non-metastatic, and 15.1% metastatic) to 32.5% overall 2016-2019 (P < 0.001), 61.2% non-metastatic (P = 0.008), 15.7% metastatic (P = NS). A higher proportion of non-metastatic patients progressed to surgery (35% vs. 31%, P = 0.020), and more received neoadjuvant therapy (16% vs. 4%, P < 0.001). Postoperative mortality following pancreatectomy at 30 and 90 days remained low at 2%. Utilization of 5FU-based chemotherapy regimens increased between 2016 and 2020. Multidisciplinary Meeting (MDM) presentation was still below the 85% target (74%) as was supportive care screening (39%, target 80%). Surgical outcomes remain world-class and there has been an appropriate shift in chemotherapy administration towards neoadjuvant timing with increasing use of 5FU-based regimens. MDM presentation rates, supportive care and overall care coordination remain areas of deficiency.

Late hepatic toxicity after breast cancer intensity-modulated radiotherapy using helicoidal tomotherapy

PurposeHelical tomotherapy (HT) is a rotational intensity-modulated radiation therapy (IMRT) technique that allows target conformal irradiation and efficient organs at risk (OAR) sparing in the case of complex target volumes and specific anatomic considerations, but increases the “low-dose bath” to non-target volumes. The aim of this study was to analyze the delayed hepatotoxicity after rotational IMRT (HT) radiation therapy for non-metastatic breast cancer. Patients and methodsThis single-center retrospective study included all non-metastatic breast cancer patients with a normal pre-radiotherapy biological hepatic function who were treated with tomotherapy between January 2010 and January 2021 and for whom the dosimetric parameters for the whole liver were assessable. A logistic regression analysis was employed. The selected covariates for the multivariate analysis were those with a P-value that was less or equal to 0.20 in the univariate analysis. ResultsForty-nine patients were included in this study: 11 patients (22%) received Trastuzumab for 1 year in tumors with an HER2-expression; 27 patients (55%) received radiation therapy for cancer of the right or bilateral breasts; 43 patients (88%) received lymph node irradiation and 41 patients (84%) received a tumor bed boost. Mean and maximum doses to the liver were 2.8Gy [0.3–16.6] and 26.9Gy [0.7–51.7], respectively. With a median follow-up after irradiation was 5.4 years (range, 6 to 115 months), 11 patients (22%) had developed delayed low grade biological hepatic abnormalities: all patients had grade 1 delayed hepatotoxicity; 3 patients (6%) had additional grade 2 delayed hepatotoxicity. There was no hepatotoxicity at grade 3 or higher. According to the univariate and multivariate analysis, Trastuzumab was a significant predictive variable of late biological hepatotoxicity (OR=4.4 [1.01–20.18], P=0.04). No other variable was statistically associated with delayed biological hepatotoxicity. ConclusionDelayed hepatotoxicity after multimodal non-metastatic breast cancer management including rotational IMRT was negligible. Consequently, the liver doesn’t have to be considered like an organ-at-risk in the analysis of breast cancer radiotherapy but future prospectives studies are needed to confirm these findings.