Recent Advances In Systemic Therapy Research Articles

USP26 as a hepatitis B virus-induced deubiquitinase primes hepatocellular carcinogenesis by epigenetic remodeling

Despite recent advances in systemic therapy for hepatocellular carcinoma (HCC), the prognosis of hepatitis B virus (HBV)-induced HCC patients remains poor. By screening a sgRNA library targeting human deubiquitinases, we find that ubiquitin-specific peptidase 26 (USP26) deficiency impairs HBV-positive HCC cell proliferation. Genetically engineered murine models with Usp26 knockout confirm that Usp26 drives HCC tumorigenesis. Mechanistically, we find that the HBV-encoded protein HBx binds to the promoter and induces the production of USP26, which is an X-linked gene exclusively expressed in the testis. HBx consequently promotes the association of USP26 with SIRT1 to synergistically stabilize SIRT1 by deubiquitination, which promotes cell proliferation and impedes cell apoptosis to accelerate HCC tumorigenesis. In patients with HBV-positive HCC, USP26 is robustly induced, and its levels correlate with SIRT1 levels and poor prognosis. Collectively, our study highlights a causative link between HBV infection, deubiquitinase induction and development of HCC, identifying a druggable target, USP26.

Current status of the cost burden of first-line systemic treatment for patients with advanced hepatocellular carcinoma in Japan, 2021-22.

Although recent advances in systemic therapies for hepatocellular carcinoma (HCC) have led to prolonged patient survival, the high costs of the drugs place a heavy burden on both patients and society. The objectives of this study were to examine the treatment regimens used as first-line systemic treatment for patients with advanced HCC in Japan and to estimate the treatment costs per regimen. For this study, we aggregated the data of patients who had received first-line systemic treatment for advanced HCC between July 2021 and June 2022. The treatment cost per month of each regimen was estimated based on standard usage, assuming an average weight of 60kg for male patients. The data were categorized by the treatment regimen, and the treatments were categorized based on the cost into very high-cost (≥1 000 000 Japanese yen [JPY]/month), high-cost (≥500 000 JPY/month) and other (<500 000 JPY/month) treatments. Of the total of 552 patients from 24 institutions whose data were analyzed in this study, 439 (79.5%) received atezolizumab plus bevacizumab, 98 (17.8%) received lenvatinib and 15 (2.7%) received sorafenib as the first-line treatment. The treatment cost per month for each of the above regimens was as follows: atezolizumab plus bevacizumab, 1 176 284 JPY; lenvatinib, 362 295 JPY and sorafenib, 571 644 JPY. In total, 82.2% of patients received high-cost regimens, and the majority of these patients received a very high-cost regimen of atezolizumab plus bevacizumab. Advances in systemic therapies for HCC have led to prolonged patient survival. However, the treatment costs are also increasing, imposing a burden on both the patients and society.

288P Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis

288P Recent advances in systemic therapy for advanced biliary tract cancer: A systematic review and meta-analysis

Surrogate endpoints for overall survival in advanced hepatocellular carcinoma: A meta-analysis.

563 Background: Recent advances in systemic therapies have resulted in improved overall survivals (OS) for patients with advanced hepatocellular carcinoma (aHCC). The most commonly utilized primary endpoint for phase III trials in aHCC is OS. A robust surrogate endpoint (SEP) can reduce time and financial costs of future trials and accelerate regulatory approvals of new therapies. We conducted a literature-based meta-analysis to evaluate SEPs for OS in aHCC. Methods: Randomized controlled trials evaluating systemic therapies in aHCC published 2007 - 2023 were identified through a systemic literature search of Cochrane and Medline databases as well as of abstracts presented at ASCO and ESMO meetings. Hazard ratios (HR) for OS and progression-free survival (PFS) and time to progression (TTP) were extracted. ΔORR was calculated as the difference in overall response rates (ORR) between control and experimental arms. Pearson correlation and mixed-effects meta-regression analyses were performed. Surrogate threshold effect (STE) was determined for each comparison when possible. A p &lt; 0.05 was considered to be statistically significant. Results: 26 trials were identified in the first-line setting with 14,827 patients and 11 trials in the subsequent-line setting with 5,316 patients. In first-line trials, immunotherapy (IO) is associated with higher ORR than other agents (p=0.003). There are statistically significant correlations between HRs of PFS/TTP/ΔORR and OS (Table). The relationship between HR-PFS and HR-OS persists in trials with or without IO, but only in trials enrolling &lt; 30% patients of non-viral aetiologies. In subsequent-line trials, there are statistically significant correlations between HRs of PFS/TTP and OS (Table). STE for HR PFS is 0.68 and 0.87 respectively for 1st and subsequent line trials. Conclusions: There are moderate to strong correlations between PFS and OS in aHCC in first-line and subsequent line trials. STE for HR-PFS of 0.68 in first-line and 0.87 in subsequent-line settings can guide sample size calculation in future clinical trials. [Table: see text]

Real-world survival outcomes and treatment patterns in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Results from the OREIOS study.

449 Background: Recent advances in systemic therapies have revolutionized the management of HCC. However, there is limited real-world data on treatment patterns and survival outcomes in pts with uHCC. OREIOS (NCT05239507) study determined the clinical characteristics, management patterns and survival outcomes in pts with uHCC from 12 countries across Asia, Latin America, and Middle East and Africa. Methods: This non-interventional, retrospective study included pts with Barcelona Clinic Liver Cancer (BCLC) stage B or C unresectable or advanced/metastatic HCC at index date (date of diagnosis), diagnosed between January 2017 and December 2019. We present the clinicodemographic characteristics, treatment patterns, median overall survival (mOS), landmark survival (12 and 24 months), and median progression-free survival (mPFS). Results: A total of 1115 pts (median [range] age: 63 [18.0-97.0] yrs) were assessed; 83.2% (928/1115) were males, 49.1% (422/859) were current or ex-smokers, 21.4% (122/571) consumed alcohol. Most common etiologies were hepatitis B (48.9% [529/1082]), hepatitis C (23.1% [250/1082]) and alcoholic liver disease (6.6% [72/1082]). At index date, 22.3% (249/1115) and 77.7% (866/1115) presented with BCLC stage B and C, respectively with main portal vein invasion in 23.5% (262/1114), &gt;50% liver involvement in 23.1% (250/1081) and extrahepatic metastases in 48.5% (541/1115). After index date, treatment modalities included systemic therapy (88.2% [992/1112] (including sorafenib [77.5%], nivolumab [21.3%], lenvatinib [19.8%], regorafenib [15.6%]), transarterial chemoembolization (TACE) (20.8% [232/1115]), and surgery (2.6% [29/1115]). The mPFS was 6.6 (95% CI 6.0, 7.2) months and mOS was 13.1 (95% CI 11.6, 14.2) months. Conclusions: Our study provides real-world data on treatment patterns and reports poor prognosis with pts reaching a mOS of ∼13 months. With novel agents and combination therapies being approved for uHCC, integrating them in routine care is important to improve survival. Alongside, further real-world studies are warranted for evaluating the change in treatment patterns and prognosis. Clinical trial information: NCT05239507 . [Table: see text]

Hepatobiliary-phase gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid MRI for pretreatment prediction of efficacy-to-standard-therapies based on Barcelona Clinic Liver Cancer algorithm: an up-to-date review.

Recent advances in systemic therapy have had major impacts on treatment strategies for hepatocellular carcinoma (HCC). The 2022 Barcelona Clinic Liver Cancer (BCLC) guidelines incorporate a new section on clinical decision-making for personalized medicine, although the first treatment suggested by the BCLC guidelines is based on solid scientific evidence. More than ever before, the appropriate treatment strategy must be selected prior to the initiation of therapy for HCC. Gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid magnetic resonance imaging (Gd-EOB-DTPA-MRI) is essential for liver imaging and the hepatobiliary phase (HBP) of EOB-MRI reflects the expression of organic anion transporting polypeptide (OATP) transporters. Molecules associated with OATP expression are relevant in the molecular classification of HCC subclasses, and EOB-MRI is becoming increasingly important with advances in the molecular and genetic understanding of HCC. In this review, we describe imaging findings for the pretreatment prediction of response to standard therapies for HCC based on the BCLC algorithm using the HBP of EOB-MRI, with specific attention to the molecular background of OATPs. A more complete understanding of these findings will help radiologists suggest appropriate treatments and clinical follow-ups and could lead to the development of more personalized treatment strategies in the future. CLINICAL RELEVANCE STATEMENT: In the coming era of personalized medicine, HBP of EOB-MRI reflecting molecular and pathological factors could play a predictive role in the therapeutic efficacy of HCC and contribute to treatment selection. KEY POINTS: • Imaging features of hepatobiliary phase predict treatment efficacy prior to therapy and contribute to treatment choice. • Wnt/β-catenin activation associated with organic anion transporting polypeptide expression is involved in the tumor immune microenvironment and chemo-responsiveness. • Peritumoral hypointensity of hepatobiliary phase reflecting microvascular invasion affects the therapeutic efficacy of locoregional to systemic therapy.

Choroidal Metastases and Choroidal Lymphoma

Since the choroid is one of the organs with the most blood supply in the body, primary and metastatic tumors are common in the choroid. While metastatic choroidal cancers are the most common tumors of the eye, choroidal lymphoma is rare. The most common cancers that metastasize to the choroid are breast cancer and lung cancer. Choroidal lymphomas can be primary or secondary. Primary lymphoma is unilateral, slow growing and mild course. However, secondary lymphomas are bilateral, rapidly developing and aggressive. Treatment and survival of patients; varies depending on the extent of the disease, the general condition of the patient and the localization of the disease. Most patients have a limited life expectancy, but recent advances in systemic therapy have significantly improved the survival of some patients. The purpose of this review is to summarize current knowledge on choroidal metastases and choroidal lymphomas, highlighting the latest findings in epidemiology, pathogenesis, diagnosis, and treatment.

Stereotactic radiosurgery for patients with brain metastases from gastroesophageal cancers.

The prognosis of patients with brain metastases from gastroesophageal (GE) cancers remains unclear despite recent advances in systemic therapies. The authors present a large single-institution experience in the use of stereotactic radiosurgery (SRS). A retrospective review of 71 GE cancer patients (64 male, 90.14%) who underwent Gamma Knife SRS was conducted. Overall, 243 brain metastases were treated and the median number of metastases per patient was 2 (range:1-21). The median age at SRS was 66 years (range: 26-85) and the median treatment day KPS was 80 (range: 50-100). The median cumulative tumor volume was 6.7cc (range: 0.27-104.76) and the median single-session margin dose was 18Gy (range: 12-20). The median overall survival after SRS was 7 months (range: 1-64). At last follow up, 54 (76.06%) patients were deceased, 8 of whom (14.81%) expired secondary to their intracranial metastases. Four patients (5.63%) experienced local tumor progression at a median time of 8 months (range: 2-13) after SRS. Ten patients (14%) experienced new remote tumor development at a median time of 4 months (range: 0-14) after SRS. Whole-brain radiation therapy (2 patients, 20%) and repeat SRS (8 patients, 80%) were used for newly developed tumors. The incidence of transient adverse radiation effects was 8.45%. In this study, the 12-month local tumor control rate was 90%. Incidences of adverse radiation effect rates were rare. The median overall survival of 7 months indicates the poor prognosis of patients with brain spread of their GE cancer.

Proximal Femur Replacements for an Oncologic Indication Offer a Durable Endoprosthetic Reconstruction Option: A 40-year Experience.

Proximal femur replacements (PFRs) are an effective surgical option to treat primary and metastatic tumors causing large bony defects in the proximal femur. Given the relative rarity of these indications, current studies on PFR for oncologic indications are generally limited by patient volume or relatively short-term follow-up. Because recent advances in systemic therapy have improved the prognosis of patients who undergo limb salvage surgery for musculoskeletal tumors, data on the long-term durability of endoprosthetic reconstructions have become increasingly important. (1) How does the long-term survival of cemented bipolar PFRs compare with patient survival in patients who underwent PFR for benign, aggressive, and metastatic tumors? (2) What are common reasons for revisions of primary PFRs? (3) Which factors are associated with survival of primary PFRs? (4) What is the survivorship free from conversion of bipolar PFRs to THA? Between January 1, 1980, and December 31, 2020, we treated 812 patients with an endoprosthetic reconstruction for an oncologic indication. All patients who underwent a primary PFR for an oncologic indication were included in this study. The study cohort consisted of 122 patients receiving a primary PFR. Eighteen patients did not reach a censored endpoint such as death, revision, or amputation within 2 years. Thirty-three patients died within 2 years of their surgery. Of the 122 patients with primary PFRs, 39 did not reach a censored endpoint and have not been seen within the past 5 years. However, the mean follow-up time for these patients was longer than 10 years. The Social Security Death Index was queried to identify any patients who may have died but might not have been captured by our database To allow for adequate follow-up, endoprosthetic reconstructions performed after December 31, 2020 were excluded. The mean age at the time of the index surgery was 48 ± 22 years. The mean follow-up time of surviving patients was 7 ± 8 years. All PFRs were performed using a bipolar hemiarthroplasty with a cemented stem, and all implants were considered comparable. Demographic, oncologic, procedural, and outcome data including prosthesis survival, patient survival, complication rates, and rates of conversion to THA were analyzed. Patient, prosthesis, and limb salvage survival rates were generated, with implant revision as the endpoint and death as a competing risk. Statistical significance was defined as p < 0.05. Generally, patients with benign or low-grade (Stage I) disease outlived their implants (100% patient survival through 30 years; p = 0.02), whereas the opposite was true in patients with high-grade, localized Stage II disease (64% patient survival at 5 years [95% CI 49% to 76%]; p = 0.001) or widespread Stage III metastatic disease (6.2% patient survival at 5 years [95% CI 0.5% to 24%]; p < 0.001). Primary PFR implant survival at 5, 10, 20, and 30 years was 97% (95% CI 90% to 99%), 81% (95% CI 67% to 90%), 69% (95% CI 46% to 84%), and 51% (95% CI 24% to 73%), respectively. Eight percent (10 of 122) of primary PFRs were revised for any reason. The most common causes of revision were aseptic loosening (3% [four of 122]), infection (3% [three of 122]), breakage of the implant (2% [two of 122]), and tumor progression (1% [one of 122]). Follow-up time was the only factor that was associated with revision of primary PFRs. Neither segment length nor stem length were associated with revision of primary. Six percent (seven of 122) of PFRs were converted to THA at a mean 15 ± 8 years from the index procedure. Survivorship free from conversion to THA (accounting for death as a competing risk) was 94% (95% CI 85% to 99%), 86% (95% CI 68% to 94%). and 77% (95% CI 51% to 91%) at 10, 20, and 30 years, respectively. Cemented bipolar PFRs for an oncologic indication are a relatively durable reconstruction technique. Given the relative longevity and efficacy of PFRs demonstrated in our study, especially in patients with high-grade or metastatic disease where implant survival until all-cause revision was longer than patient survival, surgeons should continue to seriously consider PFRs in appropriate patients. The relative rarity of these reconstructions limits the number of patients in this study as well as in current research; thus, further multi-institutional collaborations are needed to provide the most accurate prognostic data for our patients. Level III, therapeutic study.

Clinical characteristics and initial treatment patterns of patients with HCC in Korea: A multi-center real-world database analysis from the LINK research network.

e16116 Background: In Korea, liver cancer is the fifth most frequently diagnosed cancer and has the second highest cancer mortality rate. Despite recent advances in systemic therapy, patients with Hepatocellular carcinoma (HCC) continue to have poor prognoses as many are diagnosed at an advanced disease stage. To better understand the current treatment landscape and contribute to improved patient outcomes, the LINK (Liver Cancer in Korea) research network was established as a longitudinal real-world HCC database with annual data refresh. The aim was to provide current and up-to-date real-world insights into HCC patient characteristics, treatment patterns, and outcomes. Methods: LINK’s data sources are the electronic medical records of three leading academic hospitals (Asan Medical Center, Samsung Medical Center, Severance Hospital). Extracted data are standardized using a study-specific common data model to ensure comparability across hospitals. Adult patients with primary diagnosis of HCC (ICD-10: C22.0) in 2015-2020 were included and followed until death, loss to follow-up, or June 2021, whichever occurred first. Patients without valid treatment records or morphology codes or with other primary cancer diagnosis were excluded. Data on key patient and clinical characteristics, treatments, such as systemic anti-cancer therapy (SACT) regimens, and real-world outcomes were collected. Rule-based algorithms were developed to define initial treatments and lines of therapy in palliative SACT. Results: Of 25,480 HCC patients identified, 10,298 (40%) met eligibility criteria and were included in the analysis. The median age was 60 years and 19% were female. There were 74% of patients classified as Child-Pugh (CP) class A, 16% as B, 1% as C, and 9% with unknown CP at diagnosis. For albumin-bilirubin (ALBI) grade at diagnosis, 49% of patients were classified as grade 1, 45% as 2, 5% as 3, and 1% unknown. Loco-regional therapy was the most common initial treatment, with 54% and 13% of patients receiving transarterial therapy and local ablation therapy, respectively. A total of 628 patients (6%) undergone liver transplantation regardless of preceding treatments and 15% of patients were initially treated with hepatectomy. Only 2% received radiation therapy (RT) or RT in combination with cytotoxic chemotherapy as initial treatment. Among 3,026 patients who received SACT either as an initial (10%) or subsequent treatment, 67%, 20%, and 13% received 1 line, 2 lines, and 3 lines of therapy. The most common first-line SACT was sorafenib, followed by lenvatinib. Conclusions: The LINK database can serve as a multi-center research platform to facilitate fast and reliable real-world evidence generation for HCC patients. Future updates and subgroup analyses of interest can further evaluate the impact of new therapies and changes to HCC treatment guidelines in Korea.

Systemic Therapies for Metastatic Castration-Resistant Prostate Cancer: An Updated Review.

The introduction of novel therapeutic agents for advanced prostate cancer has led to a wide range of treatment options for patients with metastatic castration-resistant prostate cancer (mCRPC). In the past decade, new treatment options for mCRPC, including abiraterone, enzalutamide, docetaxel, cabazitaxel, sipuleucel-T, radium-223, 177Lu-PSMA-617, and Olaparib, have demonstrated a survival benefit in phase 3 trials. Bone-modifying agents have become part of the overall treatment strategy for mCRPC, in which denosumab and zoledronic acid reduce skeletal-related events. Recently, androgen receptor-signaling inhibitors (ARSIs) and docetaxel have been used upfront against metastatic castration-sensitive prostate cancer. Further, triplet therapy with ARSI, docetaxel, and androgen deprivation therapy is emerging. However, cross-resistance may occur between these treatments, and the optimal treatment sequence must be considered. The sequential administration of ARSIs, such as abiraterone and enzalutamide, is associated with limited efficacy; however, cabazitaxel is effective for patients with mCRPC who were previously treated with docetaxel and had disease progression during treatment with ARSI. Radioligand therapy with 177Lu-PSMA-617 is a new effective class of therapy for patients with advanced PSMA-positive mCRPC. Tumors with gene alterations that affect homologous recombination repair, such as BRCA1 and BRCA2 alterations, are sensitive to poly (adenosine diphosphate-ribose) polymerase (PARP) inhibitors in mCRPC. This review sought to highlight recent advances in systemic therapy for mCRPC and strategies to support patient selection and treatment sequencing.

Management of Locally Advanced Renal Cell Carcinoma

Renal cell carcinoma (RCC) has a natural tendency to invade the venous system with formation of a venous tumor thrombus in the renal vein, which can extend proximally into the inferior vena cava (IVC) and in some cases into the right atrium. The presence of venous involvement significantly worsens prognosis. Despite recent advances in systemic therapies, surgery remains the most effective method of treatment and in the case of complete removal of all tumor, it provides satisfactory long-term survival and must be attempted whenever possible. Several surgical techniques have been proposed, but all are associated with a high rate of perioperative complications and mortality. Minimally invasive approaches are mainly applicable for less extended IVC thrombi, while open surgery remains the gold standard for this category of patients. Most IVC thrombi can be managed without use of circulatory support by using different methods of IVC control depending on the thrombus level. However, use of cardiac bypass with or without deep hypothermic cardiac arrest is indicated in some patients with bulky intraatrial tumor thombi. In select patients presenting with IVC tumor thrombus and synchronous distant metastases, cytoreductive nephrectomy with IVC tumor thrombectomy may be considered with or without neoadjuvant systemic therapy. Surgery for RCC with venous thrombus is complex and requires experienced multidisciplinary surgical, anesthesia, and critical care teams at high-volume centers to achieve the best outcomes.

Analysis of Lenvatinib's Efficacy against Intermediate-Stage Unresectable Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) has been the standard treatment for intermediate-stage, unresectable hepatocellular carcinoma (u-HCC). However, with recent advances in systemic therapy and the emergence of the concept of TACE-refractory or -unsuitable, the effectiveness of systemic therapy, as well as TACE, has been demonstrated for patients judged to be TACE-refractory or -unsuitable. In this study, the efficacy of lenvatinib and its combination with TACE after lenvatinib was investigated in 140 patients with intermediate-stage u-HCC treated with lenvatinib mainly because of being judged to be TACE-refractory or -unsuitable. Median overall survival (OS) and progression-free survival (PFS) were 24.4 and 9.0 months, respectively, indicating a good response rate. In multivariate analysis, modified albumin-bilirubin (mALBI) grade and up to seven criteria were identified as independent factors for OS, and mALBI grade and tumor morphology were identified as independent factors for PFS. While 95% of all patients were TACE-refractory or -unsuitable, the further prognosis was prolonged by the combination with TACE after lenvatinib initiation. These findings suggest that systemic therapy should be considered for intermediate-stage u-HCC, even in patients judged to be TACE-refractory or -unsuitable. The use of TACE after the start of systemic therapy may further improve prognosis.

Targeting Epidermal Growth Factor Receptor in Head and Neck Cancer.

Head and neck squamous cell carcinomas are rising in incidence worldwide, and despite the advent of improved surgical and radiation techniques, a substantial proportion of patients have disease recurrence, where systemic therapies are the mainstay of management. Recent advances in systemic therapy include the development of epidermal growth factor receptor- and programmed death 1-targeting drugs, which have produced incremental improvements in disease outcomes. However, for most patients, responses to treatment remain elusive because of primary or acquired resistance. Novel drugs and rational drug combinations need to be tested based on biomarker identification and preclinical science that will ultimately advance outcomes for our patients. This review focuses on efforts untaken for epidermal growth factor receptor targeting in head and neck squamous cell carcinoma to date.

Recent Advances in Systemic Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma is typically diagnosed late in its course, and the median survival following diagnosis is short. The recommended therapy for localized hepatocellular carcinoma is surgical resection, but most patients are not eligible because of extensive tumor or underlying liver dysfunction.New treatments and indications for various treatments are evolving rapidly. For patients who are ineligible for liverdirected therapy or for patients showing progression on locoregionaltherapy, systemic therapy is an option if performance status and underlying liverfunction are within eligible requirements. Until 2008, no effective therapy existed for patients with advanced-stage hepatocellular carcinoma or for those who did not respond to local therapies. The molecularly targeted agents sorafenib and regorafenib have been shown to improve survival compared with best supportive care alone; a survival benefit has also been shown in the second-line setting forramucirumab and immune checkpoint inhibitors. Lenvatinib has demonstrated noninferiority to first-line sorafenib. Most recently, the combination of atezolizumab plus bevacizumab was superior to front-line sorafenib. These results have radically changed the treatment landscape for patients with advanced hepatocellular carcinoma.

Up to seven criteria in selection of systemic therapy for hepatocellular carcinoma.

Barcelona clinic liver cancer (BCLC) intermediate stage hepatocellular carcinoma is a heterogenous disease. Transarterial chemoembolization is offered as the first line therapy in this disease stage. Recent advances in systemic therapy have markedly improved outcomes even in advanced stage disease. The use of systemic therapy in BCLC intermediate stage disease may now be of therapeutic benefit in selected patients. We will focus on “the up to seven” criteria and its utility in selecting systemic therapy.

Multidisciplinary Approach to the Treatment of Advanced Hepatocellular Carcinoma in the Era of New Biologic Agents.

With recent advances in systemic therapy, an increasing number of patients with advanced hepatocellular carcinoma (HCC) are expected to benefit from surgery. However, given the complex background of the disease and frequent presence of underlying liver injury, treatment of advanced HCC is complex and the treatment principle applied to colorectal liver metastases, for which conversion surgery has been actively performed, is often not applicable to patients with HCC. To maximize the survival outcomes of patients with HCC, optimization of each step of treatment through a multidisciplinary approach is inevitable. As initial treatment, systematic removal of tumor-bearing portal territory is associated with improved survival in patients with solitary HCC, and radiofrequency ablation is also effective for small, oligo HCCs. Although the high incidence of recurrence even after curative-intent treatment is a major concern in HCC, aggressive treatment for recurrence is important, because a prolonged cancer-free interval is associated with improved overall survival. For patients with advanced disease, recently introduced molecular-targeted agents may be effective for successful conversion to surgery in initially unresectable cases, although the overall response rate of HCC to systemic therapies remains unsatisfactory as compared to that of colorectal liver metastases. This report revisits the theoretical bases for management of HCC and discusses current strategies for maximizing survival of patients with advanced HCC.

Impact of cytoreductive nephrectomy (CN) on survival in metastatic renal cell cancer (mRCC) treated with immune checkpoint inhibitors (ICI).

359 Background: The advent of ICIs has dramatically changed the treatment paradigm in mRCC. Although CN was demonstrated to improve survival in combination with cytokine-based therapies, its role is not well-defined in the ICI era. We aimed to compare survival outcomes of patients treated with ICIs, based on their CN status. Methods: The National Cancer Database was queried to identify all patients older than 18 years with mRCC who received ICIs from 2015 to 2018. Chi-Square and Mann-Whitney U tests were used to compare frequency distributions. Cox proportional hazards regression was employed for multivariate analysis of factors associated with overall survival (OS). Results: A total of 4,369 patients were identified- 36.4% (n=1589) had undergone CN. Among patients who got CN, 85.3% were treated with upfront surgery while 13.8% received prior systemic therapy ( P = 0.001). The study population was predominantly Caucasian (89.2%) and male (70.6%). Patients who underwent CN were younger (median age 61 vs. 65 years, P = &lt;0.001). Large primary tumors and clinically node-negative status were associated with higher odds of CN (T4 disease - odds ratio (OR) for 1.49, 95% CI 1.13-3.44, P = 0.03; cN0 disease - OR 1.56, 95% CI 1.23-4.56, P = 0.04). OS after 1 year was significantly higher in patients who underwent CN (66.8% vs 33.2%. P &lt;0.001). On multivariate analysis, CN was independently predictive of improved OS with a hazard ratio (HR) of 0.53 and 95% CI 0.41-0.68, P &lt;0.001. Conclusions: In this large retrospective analysis, CN was associated with improved OS among patients with mRCC receiving ICI-based therapies. Our findings suggest that despite recent advances in systemic therapies for mRCC, CN retains an important role in carefully selected patients.[Table: see text]

Recent Advances in Systemic Therapy for HCC

Recent Advances in Systemic Therapy for HCC

Stereotactic body radiation therapy for primary liver tumors: An effective liver-directed therapy in the toolbox.

The use of radiation for primary liver cancers has historically been limited because of the risk of radiation-induced liver disease. Treatment fields have become more conformal because of several technical advances, and this has allowed for dose escalation. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy, is now able to safely treat liver tumors to ablative doses while sparing functional liver parenchyma by using highly conformal therapy. Several retrospective and small prospective studies have examined the use of SBRT for liver cancers; however, there is a lack of well-powered randomized studies to definitively guide management in these settings. Recent advances in systemic therapy for primary liver cancers have improved outcomes; however, the optimal selection criteria for SBRT as a local therapy remain unclear among other liver-directed options such as radiofrequency ablation, transarterial chemoembolization, and radioembolization.