Locoregional Treatment Research Articles

Multiplication of tumor maximum diameter and number as a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage hepatocellular carcinoma.

Recent advances in treatment modalities have been made, limiting the indication of hepatic resection in the treatment strategy for hepatocellular carcinoma (HCC) patients. This retrospective study investigated the significance of multiplication of tumor maximum diameter and number (MDN) as a surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC. A total of 49 patients with Barcelona Clinic Liver Cancer intermediate-stage HCC who underwent curative hepatic resection between 2000 and 2020 were enrolled in this study. Prognostic factors of overall survival and disease-free survival, including the product of MDN, were analyzed. Patients with MDN >12 experienced significantly worse prognosis compared with those with MDN ≤12 (p=0.0395), and 5-year overall survival rates after hepatic resection were 60.0% and 23.4%, respectively. Furthermore, the disease-free survival rate of patients with MDN >12 was significantly worse compared with those with MDN ≤12 (p=0.0049), and all patients with MDN >12 experienced recurrence within 3years after hepatic resection. In the multivariate analysis, MDN >12 was identified as the only independent prognostic factor of both overall survival and disease-free survival. In addition, patients with MDN >12 suffered from uncontrollable recurrence by locoregional treatment, such as more than four intrahepatic and extrahepatic recurrences, after hepatic resection. MDN index might be a new surgical indicator for Barcelona Clinic Liver Cancer intermediate-stage HCC, and influence clinical decision-making for individual treatment strategies.

Introduction to interventional oncology: A COG Diagnostic Imaging Committee/SPR Oncology Committee White Paper.

Interventional radiology (IR) is a valuable resource when caring for pediatric solid tumor patients. As minimally invasive, image-guided procedures become more relied upon to answer challenging diagnostic questions and provide alternative therapeutic options, IR is poised to become a contributing member of the multidisciplinary oncology team. Improved imaging techniques allow for better visualization during biopsy procedures, transarterial locoregional treatments have the potential to deliver targeted cytotoxic therapy while limiting systemic side effects, and percutaneous thermal ablation can be used to treat chemo-resistant tumors of various solid organs. Additionally, interventional radiologists are able to perform routine, supportive procedures for oncology patients that include central venous access placement, lumbar punctures, and enteric feeding tube placements with high levels of technical success and excellent safety profiles.

Artificial intelligence to de-escalate loco-regional breast cancer treatment

In this review, we evaluate the potential and recent advancements in using artificial intelligence techniques to de-escalate loco-regional breast cancer therapy, with a special focus on surgical treatment after neoadjuvant systemic treatment (NAST). The increasing use and efficacy of NAST make the optimal loco-regional management of patients with pathologic complete response (pCR) a clinically relevant knowledge gap. It is hypothesized that patients with pCR do not benefit from therapeutic surgery because all tumor has already been eradicated by NAST. It is unclear, however, how residual cancer after NAST can be reliably excluded prior to surgery to identify patients eligible for omitting breast cancer surgery. Evidence from clinical trials evaluating the potential of imaging and minimally-invasive biopsies to exclude residual cancer suggests that there is a high risk of missing residual cancer. More recently, AI-based algorithms have shown promising results to reliably exclude residual cancer after NAST. This example illustrates the great potential of AI-based algorithms to further de-escalate and individualize loco-regional breast cancer treatment.

Management of Hepatocellular Carcinoma in Decompensated Cirrhotic Patients: A Comprehensive Overview.

Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for 75% of primary liver cancer cases, mostly on the basis of cirrhosis. However, the data and therapeutic options for the treatment of HCC in patients with decompensated cirrhosis are rather limited. This patient category is often considered to be in a terminal stage without the possibility of a specific treatment except liver transplantation, which is restricted by several criteria and liver donor shortages. Systemic treatments may provide a solution for patients with Child Pugh class B or C since they are less invasive. Although most of the existing trials have excluded patients with decompensated cirrhosis, there are increasing data from real-life settings that show acceptable tolerability and satisfying efficacy in terms of response. The data on the administration of locoregional treatments in such patients are also limited, but the overall survival seems to be potentially prolonged when patients are carefully selected, and close adverse event monitoring is applied. The aim of this review is to analyze the existing data regarding the administration of treatments in decompensated patients with HCC, evaluate the effect of therapy on overall survival and highlight the potential risks in terms of tolerability.

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity.

Recently, treatments for unresectable hepatocellular carcinoma (HCC) have undergone remarkable development. Various systemic chemotherapy drugs have been approved and are recommended by clinical guidelines worldwide. Although systemic treatments are effective and contribute to prolonged patient survival, their effects are unsatisfactory for some specific tumor conditions, such as macrovascular invasion. Hepatic arterial infusion chemotherapy (HAIC) is a traditional treatment for advanced HCC. As yet, there is no worldwide consensus recommending HAIC because no high-quality clinical trials have demonstrated its survival benefit. However, clinical evidence is gradually accumulating that shows its survival benefit, and it is recognized as an effective locoregional treatment for advanced HCC. Several HAIC regimens have been reported, including cisplatin monotherapy, cisplatin plus 5-fluorouracil (low-dose FP), lipiodol-suspended FP, and an oxaliplatin-based regimen. We have entered an era of chemo-diversity in the treatment of advanced HCC. This review aimed to clarify the relevance of HAIC in the era of chemo-diversity. We propose a multidisciplinary therapeutic strategy combining locoregional HAIC treatment with sequential drug therapy, with the aim of becoming cancer-free through conversion therapy.

Roles of hypoxia-inducible factor in hepatocellular carcinoma under local ablation therapies.

Hepatocellular carcinoma (HCC) is one of the most common digestive malignancies. HCC It ranges as the fifth most common cause of cancer mortality worldwide. While The prognosis of metastatic or advanced HCC is still quite poor. Recently, locoregional treatment, especially local ablation therapies, plays an important role in the treatment of HCC. Radiofrequency ablation (RFA) and high-intensity focused ultrasound (HIFU) ablation are the most common-used methods effective and feasible for treating HCC. However, the molecular mechanisms underlying the actions of ablation in the treatments for HCC and the HCC recurrence after ablation still are poorly understood. Hypoxia-inducible factor (HIF), the key gene switch for adaptive responses to hypoxia, has been found to play an essential role in the rapid aggressive recurrence of HCC after ablation treatment. In this review, we summarized the current evidence of the roles of HIF in the treatment of HCC with ablation. Fifteen relevant studies were included and further analyzed. Among them, three clinical studies suggested that HIF-1α might serve as a crucial role in the RAF treatment of HCC or the local recurrence of HCC after RFA. The remainder included experimental studies demonstrated that HIF-1, 2α might target the different molecules (e.g., BNIP3, CA-IX, and arginase-1) and signaling cascades (e.g., VEGFA/EphA2 pathway), constituting a complex network that promoted HCC invasion and metastasis after ablation. Currently, the inhibitors of HIF have been developed, providing important proof of targeting HIF for the prevention of HCC recurrence after IRFA and HIFU ablation. Further confirmation by prospective clinical and in-depth experimental studies is still warranted to illustrate the effects of HIF in HCC recurrence followed ablation treatment in the future.

Management of Locally Advanced or Metastatic Combined Hepatocellular Cholangiocarcinoma.

Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare primary liver malignancy that comprises features of hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). Due to the rarity of this tumor, the treatment of choice has not yet been defined. For resectable disease, liver resection is the mainstay treatment. However, most patients relapse or display advanced disease and were not surgical candidates. Although the majority of patients are either primarily or secondarily treated in palliative intent, no guideline recommendations or prospective trial reports exist to allow reliable evaluation of debated treatment options. We review different locoregional or medical treatment options for advanced combined hepatocellular cholangiocarcinoma (cHCC-CC) in the neoadjuvant, adjuvant, or palliative setting and discuss the possibility of predictive biomarker-guided therapeutic options.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Clinical and radiological response to locoregional and systemic treatments in well-differentiated gastroenteropancreatic neuroendocrine tumors with liver metastases treated at a reference center in Mexico.

644 Background: liver metastases (LM) from well-differentiated gastroenteropancreatic neuroendocrine tumors (wd-GEP-NET) can develop in 28-77% of patients (pts) in their lifetime. Multiple treatments can provide radiological and symptomatic response. Our aim was to evaluate responses to locoregional (LRT) and systemic (SYST) treatments in wd-GEP-NET with LM. Methods: we included consecutive records of pts with confirmed histological diagnosis of wd-GEP-NET and radiological LM, treated at our institution between 2008-2019. Relevant variables were retrospectively extracted from electronic records. Radiological response was assessed with RECIST 1.1 by radiological independent review. Results: 55 pts, 45.5% male. Median age at LM diagnosis 49 years (IQR 41-63). Primary tumor sites: 49% pancreatic, 27.3% small intestine, 11% unknown, 12.7% others. WHO 2019 grade 1, 2 and 3 in 52.7, 41.8 and 1.8%, respectively. Twentynine tumors (52.7%) were functional, with carcinoid syndrome in n20. At LM diagnosis, 91% of pts had symptomatic disease: hormonal n8, local n4, systemic n4, hormonal + local n4, local + systemic n22, hormonal + systemic n5, hormonal + local + systemic n5. LM tumoral burden was <10% in 22%, 11-50% in 43.6, > 50% in 30.9% of pts. 49.1% of pts had extra hepatic metastatic disease. LRT to LM was administered to 32 pts: TAE/TACE n26, ablation n8. SYST to 22 pts: somatostatin analog n15, Lutetium-177 n4, chemotherapy n2, everolimus n1. 1 pt did not receive treatment. Response to treatments is shown. In the LRT group, -- pts developed complications: n16 postembolization syndrome, n2 infections, n3 liver failure, n7 others. There was 1-procedure-related death. Conclusions: Patients treated with LRT at our institution achieved similar efficacy and safety results compared to those reported by previous studies.[Table: see text]

A phase I/II study of the CXCR2 inhibitor, AZD5069, in combination with durvalumab, in patients (pts) with advanced hepatocellular carcinoma (HCC).

TPS631 Background: HCC is increasing rapidly in incidence worldwide driven by a rise in chronic liver disease including non-alcoholic steato-hepatitis (NASH). Most pts are not suitable for curative or loco-regional treatments and may be candidates for systemic therapies. Immune checkpoint inhibitors combined with VEGF inhibition is a standard of care in HCC. However, a meta-analysis of 3 phase III randomised trials of PD-1 or PDL-1 inhibitors (n > 1,600 pts) with HCC suggests that pts with NASH-related HCC treated with PD-1/PDL-1 inhibitors had reduced overall survival compared with other aetiologies. Neutrophils expressing the chemokine receptor CXCR2, crucial to neutrophil recruitment in acute-injury, are highly represented in NASH-HCC. In NASH-HCC murine models, lacking response to immune-checkpoint inhibitors, AZD5069 (CXCR2 inhibitor) in combination with anti-PDL-1 suppressed tumor burden and extended survival, accompanied by an increase in tumor-associated neutrophils which switched from a pro-tumor to anti-tumor progenitor-like neutrophil phenotype. We propose that inhibition of CXCR2 may potentiate the efficacy of anti-PDL-1 inhibition in pts with HCC. Methods: In this multi-centre (n = 10) study, pts with biopsy-confirmed HCC, PS ECOG < 1, Child-Pugh A, < 1 prior systemic therapies, receive 1 of escalating doses of AZD5069 (bid, po daily) with Durvalumab (1.5 gm iv on day 1) in 28-day cycles for up to 2 years to determine the recommended phase II dose using a Keyboard design, followed by an additional cohort of pts to determine the anti-tumor efficacy of this combination using a Simon’s two-stage design (min 18, max 35 pts; target objective response rate > 30%; unacceptable response rate < 10%). Dose limiting toxicities (DLTs) are assessed during cycle 1. Disease assessments are performed 8-weekly (12-weekly after 1 year). The 1st dose cohort has been completed with no DLTs. The 2nd dose cohort opened to recruitment in September 2022. Exploratory studies (blood; pre- & on-treatment tumor and non-malignant liver biopsies) include biomarkers of CXCR2 inhibition (blood); proof-of-mechanism (tumor: expression of CXCR2, PD-L1, PD-1, CD8, CD4, CD66b, CD69); proof-of-mechanism (blood: ctDNA); drug-induced changes of mRNA expression, CXCR2 ligands & signalling pathway genes, T-cell and myeloid cell pathways, neutrophil-associated genes; predictive biomarkers (blood and tumour) include biomarkers of the CXCR2/PD-L1 immune axis; aberrant CXCR2 signalling pathways; proliferation biomarkers and CD10 (neutrophils), CD68 (macrophages), CD103 (T-regs); tumour mutational status. This study is funded by a grant from Cancer Research UK (A29287) and is co-sponsored by University of Glasgow and NHS Greater Glasgow & Clyde. Study sites are supported by the Experimental Cancer Medicine Centre Network. AZD5069 and Durvalumab are provided by Astra Zeneca. Clinical trial information: 2020-003346-36 .

Tumor treating fields (TTFields) concomitant with gemcitabine and nab-paclitaxel (GnP) for front-line treatment of locally advanced pancreatic cancer: The phase 3 PANOVA-3 study.

TPS770 Background: Tumor Treating Fields (TTFields) therapy is a loco-regional antimitotic treatment approved for glioblastoma and malignant mesothelioma. TTFields (150 kHz), with/without chemotherapy, induced antiproliferative and anticlonogenic activity in pancreatic cancer cell lines in vitro. The phase (ph) 2 PANOVA study (NCT01971281) demonstrated that TTFields therapy with gemcitabine and nab-paclitaxel (GnP; TTFields/GnP) is well-tolerated, with promising efficacy in metastatic and locally advanced pancreatic adenocarcinoma (LAPC). Despite advances in the treatment of LAPC, prognosis is poor and available therapies negatively impact quality of life (QoL); there is an unmet need for effective and tolerable treatments. Methods: PANOVA-3 (NCT03377491) is a prospective, randomized, ph 3 trial investigating the efficacy and safety of TTFields/GnP in patients (pts) with LAPC, with a planned enrollment of 556 pts. Pts with unresectable LAPC (per NCCN guidelines), ECOG PS of 0–2, and no prior treatment are eligible. Pts will be stratified by performance status and geographical region, and assigned 1:1 to TTFields/GnP or GnP alone. Standard doses of GnP will be administered on days 1, 8, and 15 of a 28-day cycle. TTFields (150 kHz) generated by the NovoTTF-200T System, will be delivered ≥ 18 h/day until local disease progression per RECIST v1.1. Pt usage is tracked by the device. Follow-up will be performed Q4W; CT scans of the chest and abdomen will be taken Q8W. After local disease progression, pts will be followed every month until death. The primary endpoint is overall survival. QoL, pain-free survival, and puncture-free survival will be compared between TTFields/GnP and GnP alone. Other secondary endpoints include progression-free survival (PFS), local PFS, objective response rate, 1-year survival rate, rate of resectability, and safety. Device Support Specialists (DSS) will provide technical and lifestyle integration training for pts and caregivers throughout TTFields therapy. The device manufacturer will also provide guidance on preventing and managing skin adverse events in line with published guidance, by means of DSS, field personnel, and various information resources. Usage information from the NovoTTF-200T System is provided to pts and physicians to facilitate discussions to optimize outcomes by maximizing time on therapy. Together, these novel support approaches help pts to confidently operate the NovoTTF-200T System with the knowledge that a multi-faceted support structure is available, ensuring TTFields therapy is seamlessly integrated into everyday life, increasing likelihood of high usage and ultimately optimizing pt outcomes. The trial is currently recruiting at 148 sites, globally. The DMC last reviewed the trial in September 2022, and suggested that the trial continue as planned. Clinical trial information: NCT01971281 .

The Role of Branched-Chain Amino Acid Supplementation in Combination with Locoregional Treatments for Hepatocellular Carcinoma: Systematic Review and Meta-Analysis.

Branched-chain amino acid (BCAA) supplementation has been linked with favorable outcomes in patients undergoing surgical or palliative treatments for hepatocellular carcinoma (HCC). To date, there has been no systematic review investigating the value of BCAA supplementation in HCC patients undergoing locoregional therapies. A systematic search of the literature was performed across five databases/registries using a detailed search algorithm according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. The search was conducted on March 23, 2022. Sixteen studies with a total of 1594 patients were analyzed. Most patients were male (64.6%) with a mean age of 68.2 ± 4.1 years, Child-Pugh score A (67.9%) and stage II disease (40.0%). Locoregional therapy consisted of radiofrequency ablation, transarterial chemoembolization or hepatic artery infusion chemotherapy. BCAA supplementation was in the form of BCAA granules or BCAA-enriched nutrient. Most studies reported improved albumin levels, non-protein respiratory quotient and quality of life in the BCAA group. Results pertaining to other outcomes including overall survival, recurrence rate, and Child-Pugh score were variable. Meta-analysis showed significantly higher levels of post-treatment serum albumin in the BCAA group (SMD = 0.54, 95% CI 0.20-0.87) but no significant differences in mortality rate (RR = 0.81, 95% CI: 0.65-1.02) and AST (SMD = -0.13, 95% CI: -0.43-0.18). BCAA supplementation is associated with higher post-treatment albumin levels. There are currently not sufficient data to support additional benefits. Further studies are needed to elucidate their value.

Plant Toxins as Potential Alternatives to Botulinum Toxin for Eye-Movement Disorder Therapy

The most successful alternative to traditional surgery for ocular muscle spasm treatment is the intramuscular injection of botulinum toxin (BTX), which allows the maintenance of the muscle dynamics and the absence of scars. However, the main BTX disadvantage is its nonpermanent effect. A possible way for overcoming this obstacle could be represented by the enzymatic surgery using plant toxins known as ribosome-inactivating proteins (RIPs). In this paper, two highly toxic RIPs, namely, ricin and stenodactylin, were considered in a preliminary study for their possible use in the treatment of strabismus and oculofacial dystonias, as alternatives to BTX. Both RIPs showed a strong cytotoxic effect against rhabdomyosarcoma cell lines and myotube differentiated cells, with stenodactylin being about 10-fold more toxic than ricin. Moreover, stenodactylin showed a much higher cytotoxicity on myoblasts than on rhabdomyosarcoma cells. In our experimental conditions, stenodactylin did not damage conjunctival cells. Despite the limitations due to in vitro experiments, our data show that the high cytotoxicity of stenodactylin allows the use of a very low dose and, consequently, of very low injection volumes. This can represent a great advantage in the case of in vivo locoregional treatment. Furthermore, it is possible to modulate the chemoablation of myocytes while destroying myoblasts, thus reducing regenerative phenomena. The risk of cytotoxicity to surrounding tissues would be strongly reduced by the low injected volume and the relative resistance of conjunctival cells. In conclusion, our data suggest that stenodactylin and ricin could represent potential candidates to substitute BTX in ocular dystonia therapy.

Liver-directed therapy of neuroendocrine liver metastases.

647 Background: While there have been major advances in the care of neuroendocrine tumors (NETs), there is still no widely adopted therapeutic sequencing in metastatic NETs. The roles and benefits of locoregional treatments need reassessment, in order to define a modern therapeutic algorithm. We examined contemporary short-term outcomes of liver-directed therapy for metastatic NETs. Methods: We conducted a population-based retrospective cohort study of patients with metastatic NETs (2000-2019) undergoing liver embolization (LE) or liver resection (LR). Outcomes were 30-day major morbidity (Clavien-Dindo grade 3-5) and/or re-admission (composite) and length of hospital stay. Modified Poisson regression accounting for clustering at the hospital level examined factors associated with outcomes in both treatment groups. Results: Overall, 1,224 LEs and 502 LRs were performed for 5,159 patients with metastatic NETs. Median length of hospital stay was 1 day (IQR 1-4) for liver embolization and 7 days (IQR 5-9) for liver resection. 30-day major morbidity and re-admission occurred after 213 LEs (17.4%) including 40 (3.3%) deaths, and 138 LRs (27.5%) including 11 (2.2%) deaths. There were 25 (2%) LEs followed by infectious complications. Factors independently associated with increased risk after LE were prior LE treatment (adjusted relative risk- aRR 0.62; 95%CI 0.44-0.88), rural residence (aRR 0.43; 95%CI 0.20-0.91) and high comorbidity burden (aRR 1.85; 95%CI 1.34-2.54). The only factor independently associated with increased risk after LR was metachronous metastases (RR 0.60; 95%CI 0.37-0.98). Conclusions: In this contemporary cohort, LE was associated with mortality similar to that of LR. Prior LE, rural residence, comorbidities, and metachronous metastatic diagnosis were associated with higher risk of major morbidity and re-admission. This information is important when discussing the use of and choice of liver-directed therapies in the multi-disciplinary management of metastatic NETs. Further characterization of long-term outcomes and patient-reported outcomes will further support decision-making, counselling, and patient preparation.

Locoregional treatment of de novo stage IV breast cancer in the era of modern oncology.

Approximately 6% of metastatic breast cancers arise de novo. While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic.

Utility of combining PIVKA-II and AFP in the surveillance and monitoring of hepatocellular carcinoma in the Asia-Pacific region.

Even though the combined use of ultrasound (US) and alpha-fetoprotein (AFP) is recommended for the surveillance of hepatocellular carcinoma (HCC), the utilization of AFP has its challenges, including accuracy dependent on its cut-off levels, degree of liver necroinflammation, and etiology of liver disease. Though various studies have demonstrated the utility of protein induced by vitamin K absence II (PIVKA-II) in surveillance, treatment monitoring, and predicting recurrence, it is still not recommended as a routine biomarker test. A panel of 17 experts from Asia-Pacific, gathered to discuss and reach a consensus on the clinical usefulness and value of PIVKA-II for the surveillance and treatment monitoring of HCC, based on six predetermined statements. The experts agreed that PIVKA-II was valuable in the detection of HCC in AFP-negative patients, and could potentially benefit detection of early HCC in combination with AFP. PIVKA-II is clinically useful for monitoring curative and intra-arterial locoregional treatments, outcomes, and recurrence, and could potentially predict microvascular invasion risk and facilitate patient selection for liver transplant. However, combining PIVKA-II with US and AFP for HCC surveillance, including small HCC, still requires more evidence, whilst its role in detecting AFP-negative HCC will potentially increase as more patients are treated for hepatitis-related HCC. PIVKA-II in combination with AFP and US has a clinical role in the Asia-Pacific region for surveillance. However, implementation of PIVKA-II in the region will have some challenges, such as requiring standardization of cut-off values, its cost-effectiveness and improving awareness among healthcare providers.

A Retrospective Study of Metastatic Renal Cell Carcinoma Patients With Brain Metastases.

Metastatic renal cell carcinoma (mRCC) involving the central nervous systemis currently an excluded subgroup of patients in the systemic treatment; for this reason, there is no solid data to support the efficacy of therapies in this subgroup. That is why it is important to describe real-life experiences in order to know if there is a special change in clinical behavior or treatment response in these kinds of patients. Patients and methods A retrospective review was performed to characterize mRCC patients diagnosed with brain metastases (BrM) during treatment at the National Institute of Cancerology of Bogota, Colombia. Descriptive statistics and time-to-event methods are used to evaluate the cohort. For the descriptive measures of quantitative variables, the mean with standard deviation was taken, and the minimum and maximum values were reported. In the case of qualitative variables, absolute and relative frequencies were used. The software used was R - Project v4.1.2 (R Foundation for Statistical Computing, Vienna, Austria). Results A total of 16 patients were included with mRCC betweenJanuary 2017 to August 2022 with a median 35.1-month follow-up, 4/16 (25%) were diagnosed with BrM at the time of screening and 12/16 (75%) during treatment. The International Metastatic RCC Database Consortium risk (IMDC) was favorable for 12.5%, intermediate for 43.7%, and poor for 25%, and not classified for 18.8%, BrM involvement was multifocal in 50% of the population and localized, brain-directed therapy was done in 43.7% of patients, predominantly palliative radiotherapy. Median overall survival (OS) for all the patients regardless of the time of metastatic presentation of the disease in the central nervous system was 53.5 months (0-70.3), and OS for cases with central nervous system involvement was 10.9 months. IMDC risk did not correlate with survival (log-rank, p=0.67). The OS for the subgroup of patients who debut with metastatic disease in the central nervous system is different from the group that developed metastasis in the progression of their disease (OS of 42 vs 3.6 months, respectively). Conclusions This is the largest descriptive study in Latin America and the second in the world from one institution that admits patients with metastasic renal cell carcinoma and central nervous system metastasis. In these kinds of patients with metastatic disease or progression to the central nervous system, there is a hypothesis that shows more aggressive clinical behavior. There is limited data on locoregional intervention to metastatic disease in the nervous system drastically, but trends show this could impact overall survival outcomes.

Irreversible electroporation for the management of pancreatic cancer: Current data and future directions.

Pancreatic cancer is currently the seventh leading cause of cancer death (4.5% of all cancer deaths) while 80%-90% of the patients suffer from unresectable disease at the time of diagnosis. Prognosis remains poor, with a mean survival up to 15 mo following systemic chemotherapy. Loco-regional thermal ablative techniques are rarely implemented due to the increased risk of thermal injury to the adjacent structures, which can lead to severe adverse events. Irreversible electroporation, a promising novel non-thermal ablative modality, has been recently introduced in clinical practice for the management of inoperable pancreatic cancer as a safer and more effective loco-regional treatment option. Experimental and initial clinical data are optimistic. This review will focus on the basic principles of IRE technology, currently available data, and future directions.

Effects of the Introduction of Modern Immunotherapy on the Outcome of Isolated Limb Perfusion for Melanoma In-Transit Metastases.

Isolated limb perfusion (ILP) is an effective locoregional treatment for melanoma in-transit metastasis, but the advent of modern effective immunotherapy, such as ICI (immune checkpoint inhibitors), has changed the treatment landscape. The primary aims of this study were to compare the characteristics of the patient population receiving ILP before and after the introduction of modern systemic treatments and to assess if outcomes after ILP were influenced by previous immunotherapy treatment. A single-centre analysis of patients that underwent ILP for melanoma in-transit metastasis between 2010 and 2021 was conducted, with patients grouped and compared by treatment time period: pre-ICI era (2010-2014) and ICI era (2017-2021). 218 patients were included. Patients undergoing ILP in the ICI era were slightly older (median age 73 vs. 68 years) compared to the pre-ICI era, with no other difference found. The overall response rate (ORR) was 83% vs. 84% and the complete response (CR) rate was 52% vs. 47% for the pre-ICI era and the ICI era, respectively. For patients that had received and failed immunotherapy prior to ILP (n = 20), the ORR was 75% and the CR rate was 50%. Melanoma-specific survival has improved, with a 3-year survival rate of 54% in the pre-ICI era vs. 86% in the ICI era. The patient population undergoing ILP for in-transit melanoma is largely unchanged in the current era of effective systemic treatments. Response rates have not decreased, and prior ICI treatment did not affect response rates, making ILP still a valid treatment option for this patient group.

The management of post-operative disease recurrence in patients with adrenocortical carcinoma: a retrospective study in 106 patients.

The management of adrenocortical carcinoma (ACC) recurrences remains controversial and we present herein our experience with post-operative ACC recurrences. Retrospective analysis in a single reference center of 106 patients with ACC recurrence. Median follow-up was 45 months, median recurrence-free survival (RFS) 12 months (IQR 6-23), and median overall survival (OS) 45 months (IQR 29-75). ACC recurrences occurred as a unique lesion (group A) in 35.8%, multiple lesions in a single organ (group B) in 20.8% and affecting multiple organs (group C) in 43.4% of patients. Baseline characteristics of patients stratified by the type of recurrence did not differ between them, apart from RFS which was significantly longer in group A. Locoregional treatments were used in 100% of patients of the group A, 68.2% in group B, and 26.1% in group C. After treatment of recurrence, 60.4% of patients became free of disease attaining a second RFS of 15 months (IQR 6-64). Margin status RX and R1, percent increase in Ki67 and recurrence in multiple organs were associated with increased risk of mortality, while adjuvant mitotane treatment and longer time to first recurrence were associated with reduced risk. Recurrence in multiple organs and systemic treatment of recurrence had a negative impact on survival from the treatment of recurrence. The present study shows that patients with ACC have a better prognosis when the disease recurs as a single lesion, and supports the use of locoregional treatments to treat disease recurrence.