Local Ablative Techniques Research Articles

Radiation therapy and IRreversible electroporation for intermediate risk prostate cancer (RTIRE)

IntroductionRadiation Therapy and IRreversible Electroporation for Intermediate Risk Prostate Cancer (RTIRE) is a phase II clinical trial testing combination of radiation therapy and irreversible electroporation for intermediate risk prostate cancerBackgroundPCa is the most common non-cutaneous cancer in men and the second leading cause of cancer death in men. PCa treatment is associated with long term side effects including urinary, sexual, and bowel dysfunction. Management of PCa is based on risk stratification to prevent its overtreatment and associated treatment-related toxicity. There is increasing interest in novel treatment strategies, such as focal therapy, to minimize treatment associated morbidity. Focal therapy alone has yet to be included in mainstream guidelines, given ongoing concerns with potentially higher risk of recurrence. We hypothesize combining focal therapy with whole gland, reduced dose radiotherapy will provide acceptable oncologic efficacy with minimal treatment associated morbidity. RTIRE is a phase II single institution, investigator-initiated study combining a local ablative technique though local irreversible electroporation (IRE) with MR guided RT (MRgRT) to treat the entire prostate. The goal is to provide excellent oncologic outcomes and minimize treatment related side effects through leveraging benefits of locally ablative therapy with established radiation treatment techniques.MethodsA total of 42 men with intermediate risk PCa per NCCN guidelines and focal grade group (GG) 2 or 3, Gleason Score (GS) 3 + 4 or GS 4 + 3, cancer in an MRI target will be enrolled. Patients with MRI visible foci of GG2/GG3 will undergo focal therapy with IRE of this lesion. Following successful focal therapy, patients will then undergo a course of reduced dose, whole gland MRgRT with either 32.5 Gy in 5 Fractions or 22 Gy in 2 fractions. The primary objective of the study is to determine safety. Secondary outcomes include evaluation of oncologic efficacy (as measured by the proportion of patients free of clinically significant cancer as defined as > Grade Group 1 at 1-year follow-up biopsy), imaging characteristics of patients pre and post RTIRE, impact on quality of life (QoL), and PSA kinetics.DiscussionCombining IRE with a reduced dose radiotherapy may offer a new treatment paradigm for PCa by both reducing treatment effects of full dose radiotherapy and minimizing the risk of recurrence observed with focal therapy.Trial RegistrationClinicaltrials.gov identifier: NCT05345444. Date of registration: April 25, 2022. Protocol Version: 6.0, July 7, 2023.

METAPANC, intensified treatment in patients with oligometastatic pancreatic cancer: Multimodal surgical treatment versus systemic chemotherapy alone—A prospective randomized controlled multicenter phase III trial.

TPS4207 Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal overall survival rate due to early metastasis and high therapy resistance. The successful introduction of intensified chemotherapeutic regimen such as FOLFIRINOX (FFX) has significantly increased response rates, disease control and overall survival. Current standards recommend systemic chemotherapy but no surgical approach in metastatic PDAC. FFX has the highest rates of response and overall survival and is a current standard of care in patients with metastatic PDAC and good performance status. Extensive surgical interventions with synchronous or metachronous metastasectomy is not recommended according to current guidelines. Retrospective data suggest beneficial outcomes in patients with hepatic oligometastasis, though prospective data from randomized clinical trials are not available. Methods: METAPANC is a prospective randomized controlled multicenter phase III trial evaluating survival and quality of life after multimodal therapy with perioperative modified FOLFIRINOX (mFFX) chemotherapy (two times 4 cycles prior to resection of the primary tumor and resection of the metastases), followed by 4 cycles of adjuvant mFFX chemotherapy (Arm A) vs. mFFX (without surgery), as standard of care first-line treatment (Arm B). Patients are eligible for randomization after 8 cycles of mFFX if they have at least stable disease on imaging according to RECIST V1.1 (Response Assessment I after 4 cycles and Response Assessment II after 8 cycles of mFFX). Patients with progressive disease will be excluded from the study. This clinical trial will focus on a well-defined patient collective with resectable PDAC and metastatic load limited to the liver with a maximum of three metastases. Patients with metachronous liver metastatic status can also be included, but must have completed adjuvant chemotherapy at least 6 months before start of study treatment. In patients randomized into Arm A with metastatic lesions located in the center of the liver local ablative techniques can be combined. In total 272 patients will be enrolled and will be randomized 1:1. The primary endpoint is overall survival, secondary endpoints are progression free survival, procedure related complications and mortality, quality of life, quality-adjusted time without symptoms and toxicity. METAPANC is accompanied by an exploratory biomarker analysis program of collecting biological and imaging samples to subsequently identify and evaluate molecular-based patient subgroups and biomarkers for identification of a potential target population which may benefit from the intensified multimodal treatment strategy. 22 German participating sites are selected. Further international sites are planned in the Netherlands, Norway, Finland and Sweden. Clinical trial information: 2023-503558-10-00.

Ablation of liver tumors : From pre-interventional imaging to post-interventional assessment

The aim of this article is to provide an overview on the most frequently applied image-guided, percutaneous, local ablative techniques for treatment of primary and secondary liver tumors. The technical procedures of microwave ablation (MWA) and radiofrequency ablation (RFA) are presented. The pre-interventional diagnostics, indications and feasibility are also discussed, taking the current national guidelines into consideration. Finally, treatment outcomes and recommendations on post-interventional imaging following local tumor ablation are presented.

Can Machine Learning Predict Favorable Outcome After Radiofrequency Ablation of Hepatocellular Carcinoma?

The standard practice for limited-stage hepatocellular carcinoma (HCC) is the resection or the use of local ablative techniques, such as radiofrequency ablation (RFA). The outcome after RFA depends on a complex interaction between the patient's general condition, hepatic function, and disease stage. In this study, we aimed to explore using a machine learning model to predict the response. A retrospective study was conducted for patients with RFA for a localized HCC between 2018 and 2022. The collected clinical, radiologic, and laboratory data were explored using Python and XGBoost. They were split into a training set (70%) and a validation set (30%). The primary end point of this study was to predict the probability of achieving favorable outcomes 12 months after RFA. Favorable outcomes were defined as the patient was alive and HCC was controlled. One hundred and eleven patients were eligible for the study. Males were 78 (70.3%) with a median age of 57 (range of 43-81) years. Favorable outcome was seen in 62 (55.9%) of the patients. The 1-year survival rate and control rate were 94.6%, and 61.3%, respectively. The final model harbored an accuracy and an AUC of 90.6% and 0.95, respectively, for the training set, while they were 78.9% and 0.80, respectively, for the validation set. Machine learning can be a predictive tool for the outcome after RFA in patients with HCC. Further validation by a larger study is necessary.

Residual cervical H-SIL after cervical conization with positive margins. Is there any associated risk factor?

Introduction: Cervical cancer is the second leading cause of death from gynecological cancer. In Argentina, it is estimated that nearly 4,500 new cases are diagnosed each year and 1,800 women die from this disease. The human papillomavirus (HPV) is a necessary but not a major cause to develop this type of cancer and it is responsible for producing both low-grade (L-SIL) and high-grade (H-SIL) squamous intraepithelial lesions (SIL) depending on the viral serotype in addition to other factors specific to the infected patient. Cervical intraepithelial neoplasia (CIN) is treated by local ablation or excision techniques with lower morbidity. The choice of treatment depends on the degree and extent of the disease, as well as the patient age, risk factors and immunity to generate spontaneous regression or persistence/recurrence. Objective: To identify clinical or pathological factors in patients who presented residual lesion (H-SIL) in the surgical specimens of both re-conization and hysterectomy (HT). Materials and methods: A retrospective, observational study was carried out at Sanatorio Güemes, Buenos Aires, Argentina. All patients that underwent cervical conization with an electric scalpel and had positive margins in the surgical specimen between January 2017 and May 2022 inclusive were analyzed. Data was obtained from 43 patients who had positive cervical conization specimen margins at our institution in the time period described above. Two patients who only had the exocervical margin involved and also 11 patients who did not meet the inclusion criteria were excluded. Among patients (30), all were reoperated (16 underwent re-conization, while in 14 patients it was decided to have a total hysterectomy). Among all the patients who underwent a new surgical procedure, residual disease was found in 10 patients (33.3%), while 20 patients (66.6%) had no residual lesion. Results: The highest percentage of patients (66.6%) did not present residual lesions in the posterior resection specimens. The parameter exhibiting the most substantial influence in our analysis was the proportion of lesion extension, exerting a significant effect on the persistence/recurrence of the disease in subsequent surgical samples (Relative Risk [RR] 7.87, 95% Confidence Interval [CI] 1.13-54.66, p < 0.01). Conclusion: This information brings us even closer to the new reports of bibliographical data: although the presence of the compromised endocervical margin is valuable for estimating the risk of disease persistence/recurrence, it is not sufficient. Therefore, there is a lack of information about the importance of other factors to predict this situation.

Combination of Local Ablative Techniques with Radiotherapy for Primary and Recurrent Lung Cancer: A Systematic Review.

In patients with early-stage or recurrent NSCLC who are unable to tolerate surgery, a benefit could derive only from a systemic therapy or another few forms of local therapy. A systematic review was performed to evaluate the feasibility and the effectiveness of radiotherapy combined with local ablative therapies in the treatment of primary and recurrent lung cancer in terms of toxicity profile and local control rate. Six studies featuring a total of 115 patients who met eligibility criteria and 119 lesions were included. Three studies evaluated lung cancer patients with a medically inoperable condition treated with image-guided local ablative therapies followed by radiotherapy: their local control rate (LC) ranged from 75% to 91.7% with only 15 patients (19.4%) reporting local recurrence after combined modality treatment. The other three studies provided a salvage option for patients with locally recurrent NSCLC after RT: the median follow-up period varied from 8.3 to 69.3 months with an LC rate ranging from 50% to 100%. The most common complications were radiation pneumonitis (9.5%) and pneumothorax (29.8%). The proposed intervention appears to be promising in terms of toxicity profile and local control rate. Further prospective studies are need to better delineate combining LTA-RT treatment benefits in this setting.

Current Trends of Alternatives to Hysterectomy in Adenomyosis: A Review Article

Adenomyosis is a common gynecological problem characterized by the growth of endometrial glands and stroma within the myometrium. Previously, the definitive diagnosis of adenomyosis was made through histopathology after a hysterectomy. However, in the last two decades, several uterine-sparing treatment options have emerged, including High-Intensity Focused Ultrasound (HIFU), which has become a promising option. HIFU is a non-invasive local thermal ablation technique that can be performed via ultrasound or MRI guidance. Additionally, “Laparoscopic uterine artery occlusion with uterus sparing pelvic plexus block and partial adenectomy for adenomyosis” has become a popular option. While conventional adenomyomectomy carries a high risk of recurrence and uterine rupture, some novel surgical techniques have been described to mitigate these complications and preserve future fertility. There are also “new surgical techniques of laparoscopic resection of adenomyoma under real-time intraoperative ultrasound elastography guidance”. Diagnostic imaging techniques such as transvaginal ultrasound, MRI, and hysteroscopic evaluation have revolutionized the diagnosis of adenomyosis and opened up possibilities for conservative treatment options. Hysteroscopy can be used for direct visualization and biopsy collection, though it is not the first-line treatment option. With the increasing incidence of adenomyosis and the desire for fertility preservation among younger patients, there is a growing need for effective uterine-sparing treatments. Bangabandhu Sheikh Mujib Med. Coll. J. 2023;2(1): 55-58

Simultaneous Delivery of Dual Inhibitors of DNA Damage Repair Sensitizes Pancreatic Cancer Response to Irreversible Electroporation.

Pancreatic ductal adenocarcinoma (PDAC) is an abysmal disease refractory to most standard therapies. Irreversible electroporation (IRE) is a local ablative technique for the clinical treatment of solid tumors, including locally advanced and unresectable PDAC, by intratumorally delivering high-intensity electric pulses to permanently disrupt cell membranes and induce cell death. But the distribution of electric field is uneven within the tumor, and in some regions, tumor cells only experience temporary perturbation to their cell membrane, a phenomenon denoted as reversible electroporation (RE). These tumor cells may survive and therefore are the main culprit of tumor relapse after IRE. We herein showed that RE, although not killing tumor cells, induced DNA double-strand breaks and activated DNA damage repair (DDR) responses. Using reactive oxygen species-sensitive polymeric micelles coloaded with Olaparib, an inhibitor of poly(ADP-ribose) polymerase (PARP), and AZD0156, an inhibitor of ataxia telangiectasia mutated (ATM), the resultant nanoformulation (M-TK-OA) disrupted both homologous recombination and nonhomologous end joining signaling of the DDR response and impaired colony formation in pancreatic cancer cells after RE. The combination of IRE and M-TK-OA significantly prolonged animal survival in both subcutaneous and orthotopic murine PDAC models and elicited CD8+ T cell-mediated antitumor immunity with a sustained antitumor memory. The efficacy of combined IRE and M-TK-OA treatments was partially attributed to the activation of cyclic GMP-AMP synthase-stimulator of interferon genes innate immune responses. Our study suggests that dual inhibition of PARP and ATM with nanomedicine is a promising strategy to enhance the pancreatic cancer response to IRE.

Local Treatment of Neuroendocrine Liver Metastases: How Effective and Safe is Stereotactic Microwave Ablation?

Abstract Background The less invasiveness of local ablation techniques such as stereotactic microwave ablation (SMWA) for the treatment of malignant hepatic lesions has made it an attractive alternative to conventional surgical resection. Aims The aim of this retrospective study was to assess the successful ablation rate of neuroendocrine tumor liver metastases (NETLM) 3 months after SMWA, the recurrence-free survival time, as well as the rate of peri- and early post interventional complications. Methods Retrospective analysis including all patients treated with SMWA for NETLM in our institution between 03/2015 and 07/2022. SMWA was performed as per the decision of the interdisciplinary tumorboard. Patients were included independent of location of primary tumors, disease stage, prior treatments. Patients underwent follow-up imaging (FU) every 1-6 months. Results 41 metastases were ablated in 21 interventions in 17 patients with a mean age of 63.6±9.7 years. A median of two lesions (range 1-4) were ablated per intervention. Mean time until first FU was 2.8±1.5 months. 39 of 41 (95.1%) lesions were fully ablated at the first FU. The two incompletely ablated lesions were treated using re-ablation and systemic treatment, respectively. A local recurrence occurred in further two ablation zones (4.9%) after 3.6 years in a patient with a progressive disease. Remaining 37 (90.2%) patients had no tumor recurrence in the ablation zone at the latest available FU (mean 24.3±17.3 months). Postinterventional length of hospital stay was a median of 1 [IQR 1;1.5]. No complications higher than Clavien Dindo Grade II occurred. Conclusions SMWA is a good minimal invasive intervention for the treatment of NETLM with low morbidity and high local efficacy.

Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation and progression are favored by different etiological risk factors including hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, non-/and alcoholic fatty liver disease (N/AFLD), and tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, etc.), and dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute to the development of HCC. The multitude and complexity of different pathomechanisms also reflect the difficulties in tailored medical therapy of HCC. Treatment options for HCC are strictly dependent on tumor staging and liver function, which are structured by the updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, and liver transplantation are valid and curative therapeutic options for early tumor stages. For multifocal and metastatic diseases, systemic therapy is recommended. While Sorafenib had been the standalone HCC first-line therapy for decades, recent developments had led to the approval of new treatment options as first-line as well as second-line treatment. Anti-PD-L1 directed combination therapies either with anti-VEGF directed agents or with anti-CTLA-4 active substances have been implemented as the new treatment standard in the first-line setting. However, data from clinical trials indicate different responses on specific therapeutic regimens depending on the underlying pathogenesis of hepatocellular cancer. Therefore, histopathological examinations have been re-emphasized by current international clinical guidelines in addition to the standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. In this review, we emphasize the current knowledge on molecular pathogenesis of hepatocellular carcinoma. On this occasion, the treatment sequences for early and advanced tumor stages according to the recently updated Barcelona Clinic Liver Cancer classification system and the current algorithm of systemic therapy (first-, second-, and third-line treatment) are summarized. Furthermore, we discuss novel precautional and pre-therapeutic approaches including therapeutic vaccination, adoptive cell transfer, locoregional therapy enhancement, and non-coding RNA-based therapy as promising treatment options. These novel treatments may prolong overall survival rates in regard with quality of life and liver function as mainstay of HCC therapy.

Safety and feasibility of irreversible electroporation for the pancreatic head in a porcine model

BACKGROUNDIrreversible electroporation (IRE) is a local non-thermal ablative technique which has been suggested as a potential cancer therapy. However, the specific anatomic characteristics of the pancreatic head make it challenging to perform any local ablation in this region. Therefore, the safety and feasibility of IRE in the pancreatic head region should be further explored.AIMTo evaluate the safety of IRE in pancreatic head region including its effects on pancreatic ducts, vessels, and adjacent gastrointestinal organs.METHODSEight landrace miniature pigs underwent IRE of pancreatic head tissue successfully, with a total of 16 lesions created. Laboratory testing including white blood cell (WBC) count and serum amylase before IRE with follow-up laboratory analysis and pathological examination at 1, 7, 14, and 28 d postablation were performed. RESULTSAll pigs tolerated the ablation procedure without serious perioperative complications. Transiently elevated WBC count and amylase were observed at 24 h post-IRE, suggesting an acute pancreatic tissue damage which was confirmed by pathological observations. Vascular endothelial cells and pancreatic duct epithelial cells in ablation zone were also positive in terminal deoxynucleotidyl transferase dUTP nick end labeling staining. There was extensive duodenum mucosa damage with local hemorrhage 24 h after ablation, while regeneration of new villous structures were observed at 7 and 28 d post-IRE. Masson’s trichromatic staining showed that the extracellular matrix was still intact in vessels and pancreatic ducts, and even in the duodenum.CONCLUSIONIRE ablation to the pancreatic head may be safe and feasible without long-term damage to the surrounding vital structures. However, risks of stress injuries in acute phase should be taken into consideration to prevent severe perioperative complications.

Substrate-Induced Dissipative and Non-Linear Effects in RF Switches: Probing Ultimate Performance Based on Laser-Machined Membrane Suspension

With the evolution of radio frequency (RF)/microwave technology, there is a demand for circuits that are able to meet highly challenging RF front end specifications. Silicon-on-insulator (SOI) technology is one of the leading platforms for upcoming wireless generation. The degradation of performance due to substrate coupling is a key problem to address for telecommunication circuits, especially for the high throw count switches in RF front ends. In this context, a fast, flexible and local laser ablation technique of the silicon handler allows for the membrane suspension of large millimeter-scale circuits. This approach enables the evaluation of the ultimate performance in the absence of the substrate, i.e., without dissipative losses and substrate-induced non-linear effects, on capacitive comb coupling structures and RF switches. Compared to high-resistivity SOI substrates, the high frequency characterization of RF membrane switches reveals a superior linearity performance with a reduction in second and third harmonics by 17.7 dB and 7.8 dB, respectively. S-parameter analysis also reveals that membrane suspension entails insertion losses that are improved by 0.38 dB and signal reflection lowered by 4 dB due to a reduced off-state capacitance. With reference to a trap-rich substrate, the membrane suspension also achieves an additional 7.8 dB reduction in the second harmonic, indicating that there is still scope for improvement in this figure of merit. The obtained results demonstrate a new way to evaluate optimized circuit performance using post-fabrication substrate engineering.

Simultaneous Gemcitabine and Percutaneous CT-Guided Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

Background Irreversible electroporation (IRE) is a new local ablation technique for pancreatic cancer. The aim of this study is to analyse the safety and effectiveness of simultaneous gemcitabine and percutaneous CT-guided IRE for locally advanced pancreatic cancer (LAPC). Materials and Methods From October 2016 to January 2018, 61 patients with LAPC who received simultaneous gemcitabine and IRE therapy (GEM-IRE group, n = 31) or IRE alone therapy (IRE group, n = 30). Routine intravenous gemcitabine chemotherapy was performed 2 weeks after IRE in both groups. Results Technical success rates were 90.0% (27/30) and 93.3% (28/30) in the GEM-IRE and IRE groups. Compared with the IRE group, the GEM-IRE group exhibited longer overall survival (OS), local tumor progression free survival (LTPFS), and distant disease free survival (DDFS) from IRE (OS, 17.1 vs. 14.2 months, p=0.031; LTPFS, 14.6 vs. 10.2 months, p=0.045; DDFS, 15.4 vs. 11.7 months, p=0.071). Multivariate Cox regression analysis results suggested that tumor volume ≤37 cm3 and simultaneous gemcitabine with IRE were significant independent prognostic factors of OS, LTPFS, and DDFS. Four major adverse reactions occurred; all of them were resolved after symptomatic treatment. Conclusions Simultaneous gemcitabine and percutaneous CT-guided IRE therapy model was effective and well-tolerated therapeutic strategy in LAPC patients.

Percutaneous Ablation of Metastatic Lymph Nodes: An Insight from the Comparison of Efficacy and Safety Between Cryoablation and Radiofrequency Ablation.

To retrospectively compare efficacy and safety of computed tomography (CT)-guided percutaneous ablation of metastatic lymph nodes (LN) between cryoablation (CA) and radiofrequency ablation (RFA). A bi-central institutional database research identified 28 patients (42 metastatic LNs) who underwent percutaneous CT-guided ablation. RFA group included 18 patients/26 tumors;CA group included 10 patients/16 tumors. Contrast-enhanced CT or MRI was used for post-ablation follow-up. Patient and tumor characteristics, technical and clinical success on a per tumor and a per patient basis and complication rates were recorded, evaluated and compared between the 2 groups. Both RFA and CA groups had the same median tumor size (2.00 vs. 2.20cm, p = 0.257), the same median follow-up time (20.50 vs. 20.00months, p = 0.923) and the same median lengthof hospitalstay(1.00 vs. 1.00days, p = 0.283). CA group had a higher median procedure time (110.50 vs. 52.00min, p = 0.001). On a per lesion basis, the overall complete response post-ablation was88.46% (23/26 lesions) in the RFA and 93.75% (15/16 lesions) in the CA group; no association was revealed between local tumor control and ablation technique (p = 0.709). No complications were recorded in both Groups. On a per patient basis, CA had a longer disease-free interval (24.00 vs. 14.50, p = 0.012) which, however, did not affect the overall survival between the two techniques (26.0 vs. 22.0, p = 0.099 for CA and RFA respectively). Our limited data suggest that CT-guided RFA and CA are equally effective on terms of efficacy and safety for the treatment of metastatic lymph nodes.

The Synergistic Role of Irreversible Electroporation and Chemotherapy for Locally Advanced Pancreatic Cancer.

Irreversible electroporation (IRE) is a local ablative technique used in conjunction with chemotherapy to treat locally advanced pancreatic cancer (LAPC). The combination of IRE and chemotherapy has showed increased overall survival when compared to chemotherapy alone, pointing towards a possible facilitating effect of IRE on chemotherapeutic drug action and delivery. This review aims to present current chemotherapeutic regimens for LAPC and their co-implementation with IRE, with an emphasis on possible molecular augmentative mechanisms of drug delivery and action. Moreover, the potentiating mechanism of IRE on immunotherapy, M1 oncolytic virus and dendritic cell (DC)-based treatments is briefly explored. Investigating the synergistic effect of IRE on currently established treatment regimens as well as newer ones, may present exciting new possibilities for future studies seeking to improve current LAPC treatment algorithms.

A rare case of insulinoma presenting with deep vein thrombosis, successfully treated with minimally invasive procedures including microwave ablation.

SummaryTreatment of insulinoma can be challenging, while surgical resection is considered the first line. When surgery is contraindicated or is refused, minimally invasive procedures such as selective arterial embolization, local ablative techniques including alcohol ablation, radiofrequency ablation and microwave ablation are being used of late. The world’s first microwave ablation of insulinoma was performed in 2015, after which there have been only a handful of reported cases. A 78-year-old female presented with painful swelling of the left lower limb. She was drowsy and was previously misdiagnosed as epilepsy when she had similar episodes since 2 years ago. She had hypoglycaemia with high serum insulin and C-peptide, and mildly high adjusted calcium, serum prolactin. MRI did not show pituitary adenoma. Lower limb venous duplex scan showed left lower limb deep vein thrombosis for which she was treated with anticoagulation. CT of the abdomen showed a tumour measuring 1.8 cm, located in the antero-superior aspect of the body of the pancreas, with the superior surface being abutted by the splenic artery and the inferior surface being 3 mm above the pancreatic duct, suggestive of an insulinoma. Selective transcatheter arterial embolization of the pancreatic tumour was attempted but was abandoned due to multiple small feeding arteries. Microwave ablation of the tumour was performed successfully. Since there was a possibility of the ablation being compromised due to the heat sink at the splenic artery, 2 mL of 99% alcohol was injected into the rim of the tumour near the artery. She was subsequently normoglycaemic. She defaulted follow up for repeat imaging of pancreas and screening for MEN1 syndrome due to the impact of the COVID-19 pandemic. Minimally invasive procedures are preferred over surgery in selected patients with insulinoma, out of which microwave ablation could be preferentially recommended due to its efficacy and minimal complications. We report the first case of MWA performed in combination with AA in successfully treating insulinoma to our knowledge. This is also the first reported case of DVT associated with isolated insulinoma prior to intervention, though it is rarely reported in MEN1 syndrome.Learning pointsNovel therapeutic minimally invasive procedures are successful in treating selected cases of insulinoma.Microwave ablation could be recommended preferentially over selective trans-arterial embolization, and radiofrequency ablation in treating insulinoma due to its efficacy and minimal complications.We report the first case of microwave ablation performed in combination with alcohol ablation in successfully treating insulinoma to our knowledge.

Locoregional Treatments for Metastatic Gastrointestinal Stromal Tumor in British Columbia: A Retrospective Cohort Study from January 2008 to December 2017.

Simple SummaryIt is not known if surgery, radiation treatment (RT) or other types of locolregional treatment (LRT) may be beneficial for patients with metastatic gastrointestinal stromal tumor (mGIST) in addition to systemic treatment. Our study aims to address this question by analyzing a cohort of 127 mGIST patients in British Columbia over a decade (from January 2008 to December 2017). We showed that mGIST patients who underwent surgery and LRT seemed to have better survival when compared to patients who did not undergo surgery and LRT. However, this treatment strategy should only be considered in patients with limited volume metastatic disease or oligoprogression while the rest of the disease is well controlled with systemic treatment. In addition, RT can offer palliative benefits such as pain relief and bleeding control. Our study, consistent with other retrospective studies, supports LRT consideration in selected mGIST patients within a multidisciplinary setting. This approach is not considered as a “standard of care” due to lack of prospective clinical trials but may improve clinical outcome for some mGIST patients.Introduction: The role of surgery and non-surgical locoregional treatments (LRT) such as radiation therapy (RT) and local ablation techniques in patients with metastatic gastrointestinal stromal tumor (GIST) is unclear. This study examines LRT practice patterns in metastatic GIST and their clinical outcomes in British Columbia (BC). Methods: Patients diagnosed with either recurrent or de novo metastatic GIST from January 2008 to December 2017 were identified. Clinical characteristics and outcomes were analyzed in patients who underwent LRT, including surgical resection of the primary tumor or metastectomy, RT, or other local ablative procedures. Results: 127 patients were identified: 52 (41%) had de novo metastasis and 75 (59%) had recurrent metastasis. Median age was 67 (23–90 years), 58.2% were male, primary site was 33.1% stomach, 40.2% small intestine, 11% rectum/pelvis, and 15.7% others. 37 (29.1%) of patients received palliative surgery, the majority of which had either primary tumor removal only (43.3%) or both primary tumor removal and metastectomy (35.1%). A minority of patients underwent metastectomy only (21.6%). A total of 12 (9.5%) patients received palliative RT to metastatic sites only (58.3%) or primary tumors only (41.7%), mostly for symptomatic control (n = 9). A few patients (n = 3) received local ablation for liver metastatic deposits with 1 patient receiving microwave ablation (MWA) and 2 receiving radiofrequency ablation (RFA). Most patients (n = 120, 94.5%) received some type of systemic treatment. It is notable that prolonged progression free survival (PFS) was observed for the majority of patients who underwent surgery in the metastatic setting with a median PFS of 20.5 (95% confidence interval (CI): 14.29–40.74) months. In addition, significantly higher median overall survival (mOS) was observed in patients who underwent surgery (97.15 months; 95% CI: 77.7-not reached) and LRT (78.98 months; 95% CI: 65.58-not reached) versus no surgery (45.37 months; 95% CI: 38.7–64.69) and no LRT (45.27 months; 95% CI: 33.25–58.66). Almost all patients (8 out of 9) achieved symptomatic improvement after palliative RT. All 3 patients achieved partial response and 2 out of 3 patients had relatively durable responses of 1 year or more after local ablation. Discussion: This study is among the first to systematically examine the use of various LRT in metastatic GIST management. Integration of LRT with systemic treatments may potentially provide promising durable response and prolonged survival for highly selected metastatic GIST patients with low volume disease, limited progression and otherwise well controlled on systemic treatments. These observations, consistent with others, add to the growing evidence that supports the judicious use of LRT in combination with systemic treatments to further optimize the care of metastatic GIST patients.

Long-Term Comparative Study on the Local Tumour Control of Different Ablation Technologies in Primary and Secondary Liver Malignancies.

Purpose: To evaluate local tumour control (LTC) by local ablation techniques (LAT) in liver malignancies. Materials and methods: In patients treated with LAT between January 2013 and October 2020 target lesions were characterised by histology, dimensions in three spatial axes, volume, vascularisation and challenging (CL) location. LAT used were: Radiofrequency Ablation (RFA), Microwave Ablation (MWA), Cryoablation (CRYO), Electrochemotherapy (ECT), and Interstitial Brachytherapy (IBT). Results: 211 LAT were performed in 155 patients. Mean follow-up including MRI for all patients was 11 months. Lesions treated with ECT and IBT were significantly larger and significantly more often located in CL in comparison to RFA, MWA and CRYO. Best LTC (all data for 12 months are given below) resulted after RFA (93%), followed by ECT (81%), CRYO (70%), IBT (68%) and MWA (61%), and further, entity-related for HCC (93%), followed by CRC (83%) and BrC (72%), without statistically significant differences. LTC in hypovascular lesions was worse (64%), followed by intermediate (82% p = 0.01) and hypervascular lesions (92% p = 0.07). Neither diameter (<3 cm: 81%/3–6 cm: 74%/>6 cm: 70%), nor volume (<10 cm3: 80%/10–20 cm3: 86%/>20 cm3: 67%), nor CL (75% in CL vs. 80% in non CL) had a significant impact on LTC. In CL, best LTC resulted after ECT (76%) and IBT (76%). Conclusion: With suitable LAT, similarly good local tumour control can be achieved regardless of lesion size and location of the target.

Stereotactic Ablative Radiotherapy for Oligometastatic Disease: A Tale of Emperor's New Clothes or New Standard of Care?

It has now been over 25 years since the conceptual paradigm of oligometastases was first postulated by Hellman and Weichselbaum [1]. In the intervening decades, tremendous enthusiasm for this paradigm has led to the adoption of various local ablation techniques targeting limited metastases, with the aim of delaying disease progression and even the possibility of cure in a significant minority of patients. As Bob Dylan once said, ‘The times they are a changing’. Whereas Dylan called on writers, critics, senators and congressman to heed his call, today we call on the clinical oncology community to evaluate the latest evidence.

Recent Advances in the Diagnosis and Management of Multiple Primary Lung Cancer

Simple SummaryWith the wide application of computed tomography and lung cancer screening, the incidence of multiple primary lung cancer, that is, the occurrence of two or more primary malignant lung tumors in a patient, has been increasingly reported. The optimal strategy for the diagnosis and treatment of multiple primary lung cancers is controversial. Surgery remains the main treatment modality, whereas other treatment methods, including radiotherapy and local ablation, are also feasible, particularly for inoperable patients. Next-generation sequencing and novel therapies, such as targeted agents and immune-checkpoint inhibitors, have provided new insights into this topic.With the wide application of computed tomography in lung cancer screening, the incidence of multiple primary lung cancer (MPLC) has been increasingly reported. Despite the established criteria, the differentiation between MPLC and intrapulmonary metastasis remains challenging. Although histologic features are helpful in some circumstances, a molecular analysis is often needed. The application of next-generation sequencing could aid in distinguishing MPLCs from intrapulmonary metastasis, decreasing ambiguity. For MPLC management, surgery with lobectomy is the main operation method. Limited resection does not appear to negatively affect survival, and it is a reasonable alternative. Stereotactic ablative radiotherapy (SABR) has become a standard of care for patients refusing surgery or for those with medically inoperable early-stage lung cancer. However, the efficacy of SABR in MPLC management could only be found in retrospective series. Other local ablation techniques are an emerging alternative for the control of residual lesions. Furthermore, systemic therapies, such as targeted therapy for oncogene-addicted patients, and immunotherapy have shown promising results in MPLC management after resection. In this paper, the recent advances in the diagnosis and management of MPLC are reviewed.