Median Survival Rate Research Articles

Pulmonary metastasectomy and repeat metastasectomy for colorectal pulmonary metastases: outcomes from the Dutch Lung Cancer Audit for Surgery

Surgical resection of recurrent pulmonary metastases in patients with colorectal cancer is an established treatment option; however, the evidence for repeat resection is limited. The aim of this study was to analyse long-term outcomes from the Dutch Lung Cancer Audit for Surgery. Data from the mandatory Dutch Lung Cancer Audit for Surgery were used to analyse all patients after metastasectomy or repeat metastasectomy for colorectal pulmonary metastases from January 2012 to December 2019 in the Netherlands. Kaplan-Meier survival analysis was performed to determine the difference in survival. Multivariable Cox regression analyses were performed to identify predictors of survival. A total of 1237 patients met the inclusion criteria, of which 127 patients underwent repeat metastasectomy. Five-year overall survival was 53 per cent after pulmonary metastasectomy for colorectal pulmonary metastases and 52 per cent after repeat metastasectomy (P = 0.852). The median follow-up was 42 (range 0-285) months. More patients experienced postoperative complications after repeat metastasectomy compared with the first metastasectomy (18.1 per cent versus 11.6 per cent respectively; P = 0.033). Eastern Cooperative Oncology Group performance status greater than or equal to 1 (HR 1.33, 95 per cent c.i. 1.08 to 1.65; P = 0.008), multiple metastases (HR 1.30, 95 per cent c.i. 1.01 to 1.67; P = 0.038), and bilateral metastases (HR 1.50, 95 per cent c.i. 1.01 to 2.22; P = 0.045) were prognostic factors on multivariable analysis for pulmonary metastasectomy. Diffusing capacity of the lungs for carbon monoxide less than 80 per cent (HR 1.04, 95 per cent c.i. 1.01 to 1.06; P = 0.004) was the only prognostic factor on multivariable analysis for repeat metastasectomy. This study demonstrates that patients with colorectal pulmonary metastases have comparable median and 5-year overall survival rates after primary or recurrent pulmonary metastasectomy. However, repeat metastasectomy has a higher risk of postoperative complications.

Is radical local therapy effective in postoperative recurrent EGFR-mutated non-small cell lung cancer?

Long-term survival can be achieved with radical local therapy in some cases of postoperative recurrence of non-small cell lung cancer (NSCLC). Here, we evaluated post-recurrence survival (PRS) after treatment of postoperative recurrent epidermal growth factor receptor (EGFR) mutated NSCLC and examined the effectiveness of radical local therapy. This multicenter prospective cohort study was conducted in 14 hospitals. The inclusion criteria for this study were patients with recurrence after radical resection for NSCLC. Information about the patient characteristics at recurrence, tumor-related variables, primary surgery, and treatment for recurrence was collected. After registration, follow-up data (e.g., treatment and survival outcomes) were obtained and analyzed. From 2010 to 2015, 505 patients with recurrent NSCLC were enrolled into the study, and 154 EGFR mutation-positive cases were included. As the initial treatment for recurrence, 111 patients (72%) received chemotherapy, 14 (9%) received chemoradiotherapy, 14 (9%) received definitive radiotherapy, and seven (5%) received surgical resection. The remaining eight patients (5%) received supportive care. The median PRS and 5-year survival rates for all cases were 64 months and 53.2%, respectively. The 5-year survival rate according to the initial treatment was as follows: supportive care, 0%; chemotherapy, 53.3% and radical local therapy, 60.1%. The six patients who received radical local treatment remained recurrence-free for more than 3 years after recurrence with only initial treatment. Although radical local therapy may be curative in some patients, chemotherapy including EGFR-TKI treatment is expected to provide long-term survival comparable to that of radical local therapy.

Transcriptome Analysis Identifies Oncogenic Tissue Remodeling during Progression from Common Nevi to Early Melanoma

Early detection and treatment of melanoma, the most aggressive skin cancer, improves the median 5-year survival rate of patients from 25% to 99%. Melanoma development involves a stepwise process during which genetic changes drive histological alterations within nevi and surrounding tissue. Here, we perform a comprehensive analysis of publicly available gene expression datasets of melanoma, common or congenital nevi (CN), and dysplastic nevi (DN), and assess molecular & genetic pathways leading to early melanoma. Our results demonstrate several pathways reflective of ongoing local structural tissue remodeling activity likely involved during the transition from benign to early-stage melanoma. These processes include the gene expression of cancer associated fibroblasts (CAF), collagens, extracellular matrix (ECM) and integrins, which assist early melanoma development and the immune surveillance which plays a substantial role at this early stage. Further, we show genes upregulated in dysplastic nevi (DN) are also overexpressed in melanoma tissue, supporting the notion DN may serve as a transitional phase towards oncogenesis. Lastly, we reveal CN collected from healthy individuals exhibit different gene signatures compared to histologically benign nevi tissue located adjacent to melanoma (adjacent nevi, AN). We show the expression profile of micro-dissected AN tissue is more similar to melanoma compared to CN, revealing the melanoma influence on this annexed tissue.

Is there a role for adjuvant therapy in radiation-induced angiosarcoma of the breast? A case report and review of the literature.

Angiosarcoma (AS) of the breast is very rare, accounting for 1% of all soft tissue breast tumors. AS may present as primary tumors of the breast or as secondary lesions usually associated with previous radiotherapy. Commonly, secondary AS affects older women (median age 67-71 years) with a clinical history of breast cancer. The preferred site of onset of RIAS is the edge of radiation fields, where radiation doses and tumor necrosis may be heterogeneous, resulting in a DNA damage and instability. Radical surgery is the treatment of choice, but no clear consensus exists on surgical management of breast AS. We describe an atypical case of relapsed RIAS after radical mastectomy, treated with new surgery and, considering the higher risk of recurrence, subsequent adjuvant chemotherapy with weekly paclitaxel. The frequency of radiation-induced angiosarcomas (RIAS) after breast-conserving surgery and radiotherapy has been increased to 0.14-0.5% among long survivors. Nevertheless, even if RIAS continues to be prognostically an extremely unfavorable cancer due to a high rate of recurrence, distant spread, and median overall survival (OS) of about 60 months, the benefits of loco-regional breast radiotherapy are clearly higher than the risk in developing angiosarcoma.

Outcomes of therapeutic penetrating keratoplasty in Pythium insidiosum keratitis managed with a combination of antibiotics.

To describe the clinical outcomes of therapeutic penetrating keratoplasty (TPK) in patients with Pythium insidiosum keratitis following treatment with anti-pythium therapy (APT) consisting of linezolid and azithromycin. A retrospective review of medical records from May 2016 to December 2019 of patients with P. insidiosum keratitis was carried out. Patients who were treated with APT for a minimum of 2 weeks and then subsequently underwent TPK were included in the study. Data on demographic characteristics, clinical features, microbiology characteristics, and intraoperative details, postoperative outcomes were documented. A total of 238 cases of Pythium keratitis were seen during the study period and 50 cases that satisfied the inclusion criteria were included. The median of the geometric mean of the infiltrate was 5.6 mm (IQR 4.0-7.2 mm). The patients received topical APT for a median of 35 days (IQR 25-56) prior to surgery. The most common indication of TPK was worsening keratitis (41/50, 82%). No recurrence of infection was observed. An anatomically stable globe was noted in 49/50 eyes (98%). The median graft survival rate was 2.4 months. A clear graft was present in 10 eyes (20%) with a final median visual acuity of 20/125 after a median follow-up period of 18.4 months (IQR 11-26 months). Graft size of less than 10 mm [OR: 5.824 (CI:1.292-41.6), P = 0.02] was found to be significantly associated with a clear graft. Performing TPK following the administration of APT has good anatomical outcomes. A smaller graft of <10 mm was associated with a higher chance of graft survival.

Immunotherapy in glioblastoma treatment: Current state and future prospects

Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis and treatment prospective. Despite the aggressive standard care, such as surgical resection and chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances and approaches. In this review, we provide an overview of the current status and progress in immunotherapy for glioblastoma, going through the fundamental knowledge on immune targeting to promising strategies, such as Chimeric antigen receptor T-Cell therapy, immune checkpoint inhibitors, cytokine-based treatment, oncolytic virus and vaccine-based techniques. At last, it is discussed innovative methods to overcome diverse challenges, and future perspectives in this area.

Successful treatment of breast metastasis from primary transverse colon cancer: A case report

The incidence of colon cancer is increasing worldwide. Treatments for colon cancer include surgery and surgery combined with chemotherapy and radiotherapy, but the median survival rate is still poor. Colon cancer most commonly metastasizes to the lymph nodes, lungs, liver, peritoneum, and brain, but breast metastasis is rare. There is no agreement on its treatment. A 23-year-old woman was admitted to our hospital for further treatment with a history of acute abdominal pain, nausea, and vomiting. Her physical examination and computed tomography scan revealed an abdominal tumor. Transverse colectomy was successfully performed. Histopathological examination revealed that the tumor was a mucosecretory adenocarcinoma with signet ring cells. The patient inadvertently found a mass in the outer upper quadrant of the right breast after four cycles of XELOX chemotherapy [oxaliplatin 130 mg/m2, d1, intravenous (iv) drip for 2 h; capecitabine 1000 mg/m2, po, bid, d1-d14]. After discussion with the patient, we performed a lumpectomy and frozen biopsy. The latter revealed that the breast tumor was intestinal metastasis. Genetic testing showed wild-type RAS and BRAF. So we replaced the original chemotherapy with FOLFIRI [irinotecan 180 mg/m2, d1, iv drip for 3-90 min; leucovorin 400 mg/m2, d1, iv drip for 2 h; 5-fluorouracil (5-FU) 400 mg/m2, d1 and 5-FU 1200 mg/(m2 d) × 2 d, continuous iv drip for 46-48 h] + cetuximab (500 mg/m2, d1, iv drip for 2 h). Serum levels of tumor markers returned to normal after several treatment cycles, and there was no evidence of tumor recurrence or metastasis. Breast metastasis from colon cancer is rare. Radical breast surgery should be avoided unless needed for palliation. Chemotherapy combined with targeted therapy should be the first choice.

Correlation between individual autoantibodies and clinical features in primary biliary cholangitis: results of a retrospective longitudinal study.

Primary biliary cholangitis (PBC) is an immune-mediated liver disease. The immunological profile seems to relate to clinical prognosis. This study aims to determine the role of autoantibodies in the course of liver disease and in the response to ursodeoxycholic acid. Between January 2016 and December 2020, 143 patients with PBC who underwent immunological liver profile evaluation were enrolled. All data were extracted retrospectively from electronic clinical records. Chi-square test, Fisher's exact test and Mann-Whitney test were used to evaluate the relationship between autoantibodies and biochemical parameters, clinical outcomes and therapeutic response scores. A significance level of 0.05 was used. Antimitochondrial antibodies were present in 91.6%, antiglycoprotein-210 antibody (anti-gp210) in 18.2% and anti-Sp100 in 19.6% of patients. The incidence of liver-related death was higher in patients with autoimmune hepatitis variants. The occurrence of cirrhosis or portal hypertension was not linked to the presence of any of the autoantibodies tested. No relationship was found with the probability of dying or being transplanted. Patients with anti-Sp100 antibodies had higher baseline levels of aspartate aminotransferase and alanine aminotransferase and lower immunoglobulin M levels. Patients with anti-gp210 were more likely to have a lower median transplant-free survival rate and higher median risk of liver transplant or liver-related death using the GLOBE and UK-PBC scores. Our findings confirm a strong association between anti-gp210 antibodies and a worse outcome. The association between anti-Sp100 and hepatic lesions requires further elucidation.

The Cutaneous Squamous Cell Carcinoma - An Update

The cutaneous squamous cell carcinoma (CSCC) is the second most common nonmelanoma skin cancer with an increasing incidence rate. Patients presenting with high-risk lesions associated with locally advanced or metastatic CSCC face high rates of recurrence and mortality. Selective literature review based on PubMed and consideration of current guidelines "Aktinische Keratosen und Plattenepithelkarzinom der Haut" and "Prävention von Hautkrebs". Complete surgical excision with histopathological control of excision margins is the gold standard in the treatment of primary CSCC. Radiotherapy can be used as an alternative treatment of inoperable CSCCs. In 2019, the PD1-antibody cemiplimab, has been approved for the treatment of locally advanced and metastatic CSCC by the European Medicines Agency. After 3 years of follow up, Cemiplimab shows overall response rates of 46 %, the median overall survival and median response rate had not been reached yet. Additional immunotherapeutics, combinations with other agents and oncolytic viruses are all potentially worth study to try, so clinical trial data will be forthcoming over the next few years to guide optimal use of these agents. Multidisciplinary board decisions are mandatory for all patients with advanced disease who require more than surgery. Further development of existing therapeutic concepts, identification of new combination therapies and the development of new immunotherapeutics will be the key challenge over the next few years.

Prognostic factors in T4b gastric cancer after surgery: A more balanced and sequential therapy for patients?

This study aimed to evaluate the prognostic factors in T4b gastric cancer (GC) in order to improve future therapeutic strategies. We retrospectively analyzed the medical records of 43 patients with advanced GC who underwent surgery and were surgically or pathologically diagnosed with T4b GC. The overall survival (OS) rate of patients with T4b GC was analyzed, and univariate and multivariate analyses were performed to identify clinicopathological factors that were independently associated with OS. In addition, we assessed the relationship between postoperative chemotherapy and laboratory parameters 4 weeks post-surgery. The proportion of patients with invasion of cancer in organs, including the pancreas, transverse colon, and liver, were 58.1%, 18.6%, and 14.0%, respectively. The proportion of patients who exhibited distant metastases was 44.2%, and R0 resection was achieved in 30.2% of patients. A total of 69.8% of patients underwent postoperative chemotherapy. The median survival rate was 12.3 months. Upon multivariate analysis, the presence of distant metastases (P = 0.01, HR; 3.48), the use of postoperative chemotherapy (P = 0.0004, HR; 0.12), and R0 resection (P < 0.0001, HR; 0.14) were significantly correlated with OS. Patients who did not undergo postoperative chemotherapy showed significantly higher levels of inflammatory parameters and lower levels of nutritional parameters 4 weeks after surgery than those who did. We evaluated that the presence of distant metastases was significantly associated with a poor prognosis, and the use of postoperative chemotherapy and R0 resection was significantly associated with a better prognosis in patients with T4b GC. It would be more important for a T4b GC treatment to balance between therapeutic tolerance for postoperative chemotherapy and surgical therapeutic effect.

PROGNOSTIC VALUE OF LOW-DOSE ADRENOCORTICOTROPIC HORMONE TEST IN CRITICALLY ILL PATIENTS.

Background: Previous trials evaluated the incidence of critical illness-related corticosteroid insufficiency (CIRCI) using 250 μg adrenocorticotropic hormone (ACTH). However, this supraphysiological dose could result in false-positive levels. We aimed to determine the incidence of CIRCI in septic patients using a 1 μg ACTH stress test. Methods: We conducted a prospective cohort study on 39 patients with septic shock. Critical illness-related corticosteroid insufficiency was defined as a Δ max cortisol <9 μg/dL after 1 μg ACTH stress test. The primary outcome of the study was death. Secondary outcomes included days of vasopressors, days of mechanical ventilation (MV), amount of fluid per day, the incidence of acute kidney injury (AKI), and days of intensive care unit (ICU) stay. Results: The incidence of CIRCI in our cohort was 43.6% using 1 μg ACTH. There were no significant differences between groups in terms of ICU scores, laboratory investigations, vasopressors, MV days, amount of fluid per day, and the ICU stay ( P = > 0.05). The CIRCI group had lower median survival and survival probability rates (5 days and 48.4%, respectively) compared with the non-CIRCI group (7 days and 49.5%, respectively). In addition, the CIRCI group had a shorter time to develop AKI and a higher probability of developing AKI (4 days and 44.6%, respectively) in comparison with the non-CIRCI group (6 days and 45.57%, respectively). Conclusion: We concluded that the CIRCI group had a lower mean survival rate and a higher incidence of AKI. We recommend the use of 1 μg ACTH test in septic shock patients to identify this subgroup of patients.

Abstract 1392: Integrative biomarker analysis of regorafenib plus nivolumab (RegoNivo) in unresectable hepatocellular carcinoma (uHCC): A multicenter phase 2 RENOBATE trial

Abstract Regorafenib plus nivolumab (RegoNivo) combination has shown promising anti-cancer activity in multiple cancer types. REBNOBATE trial is a single-arm multicenter phase 2 trial of first-line RegoNivo in patients (pts) with uHCC (NCT04310709). Here we report the clinical outcomes of the RENOBATE study and integrative biomarker analysis using circulating tumor DNA (ctDNA) and single cell RNA sequencing (scRNA-seq) analysis. Method: Adult pts with ECOG PS 0 or 1, BCLC stage B or C, and no prior systemic therapy were eligible for the study. Pts received nivolumab 480 mg iv, every 4 wks, and regorafenib 80 mg daily po, 3 wks on/1 wk off, every 4 wks. Tumor response was assessed according to RECIST v1.1 every 8 wks. ctDNA analysis was performed using the Guardant 360 CDx (n=42). scRNA-seq was performed using PBMCs at baseline (e.g., C1D1) and on treatment (eg., C1D15) from early progression (EP) group (14 pts with PD or tumor burden increases towards PD on the 1st evaluation) and long-term response (LR) group (15 pts with PR or SD &amp;gt; 6 months). Results: 42 pts were enrolled. Response rates were 31.0% and median progression-free survival (was 7.4 mo (95% CI, 4.2-13.0) and 1-year OS rate was 80.5% (95% CI, 63.0-90.3%). Aberrations of Wnt/β-Catenin and PI3K/mTOR pathways identified in ctDNA were not associated with efficacy outcomes. scRNA-seq revealed that genes upregulated in immune cells on C1D15 (vs. C1D1) were associated with immune activation and regulation of angiogenesis. Unsupervised clustering identified 13 immune subsets; among them, classical monocyte showed the most prominent changes in their proportion and gene expression profiles. After RegoNivo treatment, CD8 clusters had enhanced expressions of genes related to cytotoxicity, tissue homing (i.e., CXCR6, CX3CR1, and CXCR3) and proliferation (MKI67), and monocyte clusters showed an enrichment of the gene signatures representing polarization towards M1-related features. Importantly, the enrichment of cytotoxic features of the T cell clusters and M1-polarizing features of monocyte clusters were more pronounced in LR group than in EP group. From the analysis of differentially expressed genes monocyte clusters between the EP and LR groups, a surface molecule ‘X’ was identified as a potential biomarker involved in resistance to RegoNivo. RegoNivo showed promising efficacy outcomes in pts with uHCC. Through scRNA-seq of serial PBMCs, we identified enhanced cellular immune responses induced by RegoNivo and a potential predictive marker for immunotherapy in pts with uHCC. Our study highlighted that regorafenib might synergize with anti-PD-1 in pts with uHCC. Association between differential features of T cell and monocyte clusters induced by this combination and distinct clinical outcomes highlights the importance of immune-modulation in HCC pts suggesting a potential to further harness these signals Citation Format: Hyung-Don Kim, Seyoung Jung Jung, Baek-Yeol Ryoo, Min-Hee Ryu, Beodeul Kang, Hong Jae Chon, Jung Yong Hong, Ho Yeong Lim, Jeong Seok Lee, June-Young Koh, Changhoon Yoo. Integrative biomarker analysis of regorafenib plus nivolumab (RegoNivo) in unresectable hepatocellular carcinoma (uHCC): A multicenter phase 2 RENOBATE trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1392.

Abstract 1083: MEKi and SOS1i as a combination treatment option for KRAS mutant endometrial cancer

Abstract Endometrial cancer (EC) is the most common cancer of the female genital tract, resulting in over 75,000 deaths per year worldwide. Despite recent advances in medical oncology research, chemo- and radiotherapy are still the standard of care treatments for recurrent or metastatic EC and prognosis for these patients remains poor, with median survival rates of less than one year. Approximately 15-30% of the more common type I EC harbors oncogenic KRAS mutations, which have been linked to disease progression. Preclinical studies have shown that MEK inhibitors exhibit strong anti-tumor activity in KRAS mutant EC models. In the clinical setting however, MEKi monotherapy has proven unsuccessful in KRAS mutant EC patients, suggesting that combinations with other targeted agents may be needed to achieve increased signaling modulation and enhanced therapeutic activity. As suggested by our previous work in KRAS mutant lung, colorectal and pancreatic cancer, the combined inhibition of MEK and SOS1 may overcome adaptive resistance to MEKi by blocking SOS1-mediated reactivation of MAPK signaling. We evaluated whether this hypothesis can also be applied in the context of EC. Here we treated preclinical models of EC with a combination of clinically relevant doses of a MEKi (trametinib) and BI-3406, a potent and selective orally bioavailable SOS1 inhibitor. Treatment of KRAS mutant EC cells resulted in decreased activity of the KRAS-MAPK pathway, as measured by ERK phosphorylation. This effect was further enhanced by co-treatment with BI-3406. In vivo, the combination of MEKi with SOS1i synergistically decreased tumor growth in two KRAS G12D mutant orthotopic patient-derived xenograft models of EC. The anti-tumor effect of the combination was comparable to the effect of paclitaxel, the standard of care treatment in EC. This suggests that the combination of MEKi with SOS1i may be a potential therapeutic approach for the treatment of EC patients with tumors harboring KRAS mutations. Citation Format: Kaja Kostyrko, Melanie Hinkel, Marco H. Hofmann, Francesca Trapani. MEKi and SOS1i as a combination treatment option for KRAS mutant endometrial cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1083.

Abstract 2709: Leukosome-based siRNA strategy for targeting ribosomal protein L39 (RPL39) in metaplastic breast cancer

Abstract Metaplastic breast cancer (MpBC) is a rare and highly aggressive subset accounting for &amp;lt;5% of all BCs. Clinically, MpBCs exhibit the most dismal prognosis of all BC subtypes, with a median survival rate of 8 months in patients with metastatic disease. The main therapeutic option for MpBC remains standard chemotherapy, despite known resistance to most cytotoxic drugs. We recently reported that ~40% of MpBC patient samples display a gain-of-function oncogenic mutation (A14V) in ribosomal protein RPL39, which is responsible for treatment resistance, cancer stem cell self-renewal, and lung metastases. We also showed that high RPL39 levels were associated with worse survival in patients with MpBC. Collectively, these findings support the rationale of targeting this ubiquitous genetic marker in MpBC. This study was aimed to design an innovative targeted therapy against RPL39 by combining a small interfering RNA (siRNA) strategy (siRPL39) with biomimetic lipid nanoparticle (LNP) technology for in vivo delivery to MpBC cells. These LNPs referred to as “leukosomes” incorporate membrane proteins from circulating leukocytes to facilitate evasion of immune clearance, enhance tropism towards inflamed endothelium such as the tumor-associated one, and improve siRNA internalization into the tumor mass. For leukosomes synthesis, we adapted a microfluidic device to incorporate membrane proteins from leukocytes within lipid bilayers. This technique retained all the physical and biological features of leukosomes, combined with high siRNA loading efficiency. We evaluated in vitro uptake and efficacy of siRPL39-loaded leukosomes in MpBC cell lines. We found that fluorescently labeled siRPL39 was rapidly internalized by leukosomes into MpBC cells demonstrating efficient and uniform uptake without inducing cytotoxicity. Treatment of MpBC cells with siRPL39-loaded leukosomes exhibited significantly knockdown of RPL39 mRNA, further supporting that the observed siRNA internalization results in potent and specific gene silencing. Notably, siRPL39-loaded leukosomes inhibited in vitro cell proliferation as compared with control siRNA leukosomes, indicating a key role of RPL39 in MpBC growth. Next, we sought to evaluate functional gene silencing of siRPL39-loaded leukosomes in vivo. We established MpBC patient-derived xenografts (PDXs) in the mammary fat pad of humanized NSG mice. We revealed that leukosomes formulation enables siRPL39 accumulation and functional gene silencing in MpBC tumors after local administration, without causing overt toxicity. Overall, our findings highlight RPL39 as a novel therapeutic target in MpBC and provide proof of principle for the development of leukosome-based siRNA drugs to improve delivery to cancer cells. Ongoing studies are directed to evaluate biodistribution, in vivo silencing and therapeutic effects of siRPL39-leukosomes after systemic administration. Citation Format: Maria Florencia Chervo, Chiara Mancino, Federica Giordano, Tejaswini P. Reddy, Wei Qian, Jianying Zhou, Liliana Guzman-Rojas, Roberto R. Rosato, Francesca Taraballi, Jenny C. Chang. Leukosome-based siRNA strategy for targeting ribosomal protein L39 (RPL39) in metaplastic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2709.

Survival and Prognostic Factors Predicting Outcomes of Patients with Primary Non-Metastatic Colorectal Cancer who have not had Curative Intervention

Abstract Background: The natural progression and life expectancy of patients following a diagnosis of treatable colorectal cancer who receive only symptomatic treatment, nonoperative palliative therapy, or noncurative surgical interventions are relatively unknown. Objectives: The objective of this retrospective study was to examine the survival of patients following a diagnosis of primary nonmetastatic colorectal cancer who did not undergo major surgery for the purpose of curative treatment. Design: A retrospective observational study. Study Settings: Department of Colorectal Surgery, King’s College Hospital, London. Patient and Methods: A retrospective study of patients with stages I–III colorectal cancer who had not undergone noncurative surgery, palliative chemotherapy, or radiotherapy between 2012 and 2019 was conducted. Multivariate and univariate analyses were used to evaluate the prognostic factors associated with overall survival (OS). Main Outcome Measure: OS. Sample Size: A total of 78 patients. Results: A total of 78 patients were enrolled in this study. The median survival rate was 296 days or 9.7 months, and the mean survival rate was 385 days (15–1894 days). The 1- and 2-year OS rates were 37.2% and 3.8%, respectively. Univariate analysis revealed that three parameters were statistically significant for OS with a significant correlation with performance status (PS) (P = 0.004), tumor stage (pT) (P = 0.030), and lymph node metastasis (pN) (P = 0.001). Multivariate analysis revealed that pN2 (hazard ratio: 2.19, 95% confidence index: -1.1–4.4) and PS 3 and 4 (hazard ratio: 0.525, 95% confidence index: 0.3–1.0, P = 0.026) were prognostic factors associated with OS. Conclusion: Operable colorectal cancer patients without surgical resection have an OS rate of &lt;1 year; a higher T and N stage is associated with adverse prognosis. Limitations: Our study is limited by its retrospective nature and small sample size. In addition, patients underwent various palliative interventions based on their unique clinical, pathological, and social needs. Conflict of Interest: The authors have no conflict of interest to declare.

Resolution of Pain after Percutaneous Image-Guided Cryoablation of Extraperitoneal Endometriosis

PurposeTo retrospectively evaluate the relief of pain after percutaneous image-guided cryoablation of symptomatic extraperitoneal endometriosis (EE). Material and MethodsFrom 2017 to 2022, cryoablation of EE was performed at a single institution on a total of 47 lesions in 42 consecutive patients (median age, 37 years; interquartile range [IQR], 33–39.5 years). Patient and procedural characteristics were reviewed retrospectively. Tolerance and outcomes in terms of pain and patient satisfaction were evaluated. ResultsThe median follow-up duration was 13.5 months (IQR, 1.1–37.7 months) after cryoablation. The median pain-free survival rate was 93.8% (95% confidence interval [CI], 77.3–98.4) at 6 months and 82.7% (95% CI, 58.8–93.5) after 12 months. Pain decreased from a median of 8/10 (IQR, 7–9) on the visual analog scale to 0/10 (IQR, 0–1) at the last follow-up (P < .0001). The median Patient Global Impression of Change score recorded at the last follow-up was 1/7 (IQR, 1–2). The efficacy rate of cryoablation to avoid secondary surgery was 92.8% (39/42) per patient and 93.6% (44/47) per nodule treated. Four patients (9.5%, 4/42) experienced an adverse event in the days following the procedure, and 1 patient (2%) experienced a severe adverse event. ConclusionsPercutaneous cryoablation is safe and effective in significantly reducing pain and obtaining local control of EE.

Clinical pathological characteristics and treatment outcomes of renal cell carcinoma (RCC): a retrospective study from Sudan.

Worldwide, renal cell carcinoma comprises 2.2% and 1.8% of global cancer incidence and mortality, respectively. Studies of epidemiology, treatment modalities and outcomes of renal cell carcinoma (RCC) in Sudan are scarce. To address this shortcoming, we evaluated baseline information on the epidemiology, types of treatment and outcomes of RCC at Gezira Hospital for Renal Diseases and Surgery (GHRDS) and the National Cancer Institute (NCI). We performed a retrospective, descriptive study of all patients with RCC, who were treated in GHRDS and NCI from January 2000 to December 2015. A total of 189 patients with RCC were identified over the study period. Tumours were more common among male patients (56%) and involved the left kidney in 52% of cases. The median age at diagnosis was 57 years (range: 21-90 years). Loin pain was the most frequent symptom (n = 103 patients) followed by weight loss (n = 103 patients) and haematuria (n = 65 patients). The most common histopathologic type of RCC was clear cell (73.5%), followed by papillary (13.8%) and chromophobe (1.6%). The relative frequencies of stages I-IV were 3.2%, 14.3%, 29.1% and 53.4%, respectively. The overall median survival rate was 24 months, and the 5-year survival rate was 40%. The 5-year survival rate in stages I-IV was 95%, 83%, 39%, and 17%, respectively. Advanced stages and higher-grade tumour were associated with worse survival. The median survival of stage IV patients was better for patients who underwent nephrectomy (11.0 months) compared to those who did not undergo nephrectomy (4.0 months) (p value = 0.28). Our findings reveal poor outcomes for patients with RCC in Sudan, which is most likely due to the high proportion of patients presenting with advanced stages at the time of initial presentation.

Median survival following geriatric hip fracture among 17,868 males from the Veterans Health Administration.

The expected value of treatments for geriatric femoral neck fracture is influenced by the predicted duration of survival after injury. Specifically, total hip arthroplasty is more suited for patients likely to live long enough to reap its longer-term benefits. For predicting short- and medium-term survival, there are many tools available, but for longer-term survival prognosis the current literature is insufficient. Our hypothesis is that patient age at the time of injury correlates with median life expectancy and survival rates, and these values can anchor a prediction regarding a given patient's life expectancy. We therefore sought to determine median and fractional survival rates at 30 days, and 1, 2, 5 and 10 years after surgery for a large cohort of elderly patients with hip fracture as a function of age. 17,868 male patients, 65-89 years of age, treated surgically for hip fracture within the Veterans Affairs system were assessed. From this set, 10,000 patients were randomly selected, and their ages at surgery and death (if any) were recorded at least 10 years post-operatively. Median and fractional survival rates were recorded at 1 month and 1, 2, 5, and 10 years. The mathematical relationship between age and median survival was determined. All findings from the 10,000-patient cohort were compared to corresponding values of the remaining 7,868 patients, to assess the predictive power of the initial observations. The median survival rate for the entire cohort was 2.2 years, with 90.4% of the group surviving at 30 days. The percentage of the cohort surviving at 1, 2, 5 and 10 years after treatment was 64.5%, 52.3%, 27.1% and 8.9% respectively. Median survival was approximately (13 - (0.13 × age-at-time-of-surgery) years for patients of all ages. Median survival after geriatric hip fracture can be accurately predicted by the patient's age at the time of injury. Median survival and fractional survival at key milestones can help estimate life-expectancy and thereby help guide treatment.

The clinical role of radiofrequency ablation for early-stage hepatocellular carcinoma in an advanced aging society.

It is unclear whether prognosis differs by age for early-stage hepatocellular carcinoma (HCC). We aimed to examine prognosis and recurrence after radiofrequency ablation (RFA) for early-stage HCC and to determine its prognostic factors for different age groups. This retrospective study enrolled 1079 patients with initial early-stage HCC treated with RFA at two institutions. All patients in this study were divided into four groups: <70 years old (group1, n=483), 70-74 years old (group2, n=198), 75-79 years old (group3, n=201), and ≥80 years old (group4, n=197). Prognostic factors were evaluated by comparing survival and recurrence rates between each group. The median survival time and 5-year survival rates for each group were 113 months and 70.8% in group1, 99.2 months and 71.5% in group2, 91.3 months and 66.5% in group3, and 71 months and 52.6% in group 4, respectively. Group4 had a significantly shorter survival than the other groups (p<0.05). There were no significant differences in recurrence-free survival among the groups. In group4, the most common cause of death was non-liver-related disease (69.4%). In all groups, mALBI grade was a factor contributing to prolonged prognosis, but only in group4 performance status (PS) was a significant factor (HR: 2.46, 95% CI: 1.16-3.00, p=0.009). For early-stage HCC in the elderly, preoperative evaluation of PS and management of other diseases may contribute to a prolonged prognosis. This article is protected by copyright. All rights reserved.

Interventional oncological treatment of hepatocellular carcinoma (HCC) - A single-center long-term evaluation of thermoablation techniques like LITT, MWA, and TACE in a multimodal application over 26 years

PurposeThe purpose of the study is to retrospectively evaluate the development and technological progress in local oncological treatments of hepatocellular carcinoma (HCC) by means of ablation techniques like laser interstitial thermal therapy (LITT), microwave ablation (MWA) and transarterial chemoembolization (TACE) in a multimodal application.MethodThis retrospective single-center study uses data generated between 1993 and 2020 (1,045 patients). Therapy results are evaluated using survival rates of Kaplan-Meier estimator, Cox proportional hazard regression and log-rank test.ResultsMedian survival times in group LITT (25 patients) are 1.6 years, and, 2.6 years for LITT + TACE (67 patients). For LITT only treatments 1-/3-/5-year survival rates scored 64%, 24% and 20%. Results for combined LITT + TACE treatments were 84%, 37% and 14%. Median survival time in group MWA (227 patients) is 4.5 years. Estimated median survival time for MWA + TACE (108 patients) leads to a median survival time of 2.7 years. In group MWA the 1-/3-/5-year survival rates are 85%, 54%, 45%. Group MWA + TACE shows values of 79%, 41% and 25%. A separate group of 618 patients has been analyzed with TACE as monotherapy. Median survival time of 1 year was estimated in this group. 1-/3-/5-year survival rates are 48%, 15% and 8%. - Cox regression analysis showed that the different treatment methods are statistically significant predictors for survival of patients.ConclusionsTreatments with MWA resulted in best median survival rates, followed by MWA + TACE in combination. Survival rates of MWA only are significantly higher vs. LITT, vs. LITT + TACE and vs. TACE monotherapy.