A Classification-Based Adaptive Segmentation Pipeline: Feasibility Study Using Polycystic Liver Disease and Metastases from Colorectal Cancer CT Images.

Automated segmentation tools often encounter accuracy and adaptability issues when applied to images of different pathology. The purpose of this study is to explore the feasibility of building a workflow to efficiently route images to specifically trained segmentation models. By implementing a deep learning classifier to automatically classify the images and route them to appropriate segmentation models, we hope that our workflow can segment the images with different pathology accurately. The data we used in this study are 350 CT images from patients affected by polycystic liver disease and 350 CT images from patients presenting with liver metastases from colorectal cancer. All images had the liver manually segmented by trained imaging analysts. Our proposed adaptive segmentation workflow achieved a statistically significant improvement for the task of total liver segmentation compared to the generic single-segmentation model (non-parametric Wilcoxon signed rank test, n = 100, p-value << 0.001). This approach is applicable in a wide range of scenarios and should prove useful in clinical implementations of segmentation pipelines.

Sublobar Resection, Stereotactic Body Radiation Therapy, and Percutaneous Ablation Provide Comparable Outcomes for Lung Metastasis-Directed Therapy.

BACKGROUND: Prolonged survival of patients with metastatic disease has furthered interest in metastasis-directed therapy (MDT). RESEARCH QUESTION: There is a paucity of data comparing lung MDT modalities. Do outcomes among sublobar resection (SLR), stereotactic body radiation therapy (SBRT), and percutaneous ablation (PA) for lung metastases vary in terms of local control and survival? STUDY DESIGN AND METHODS: Medical records of patients undergoing lung MDT at a single cancer center between January 2015 and December 2020 were reviewed. Overall survival, local progression, and toxicity outcomes were collected. Patient and lesion characteristics were used to generate multivariable models with propensity weighted analysis. RESULTS: Lung MDT courses (644 total: 243 SLR, 274 SBRT, 127 PA) delivered to 511 patients were included with a median follow-up of 22 months. There were 47 local progression events in 45 patients, and 159 patients died. Two-year overall survival and local progression were 80.3% and 63.3%, 83.8% and 9.6%, and 4.1% and 11.7% for SLR, SBRT, and PA, respectively. Lesion size per 1 cm was associated with worse overall survival (hazard ratio, 1.24; P = .003) and LP (hazard ratio, 1.50; P < .001). There was no difference in overall survival by modality. Relative to SLR, there was no difference in risk of local progression with PA; however, SBRT was associated with a decreased risk (hazard ratio, 0.26; P = .023). Rates of severe toxicity were low (2.1%-2.6%) and not different among groups. INTERPRETATION: This study performs a propensity weighted analysis of SLR, SBRT, and PA and shows no impact of lung MDT modality on overall survival. Given excellent local control across MDT options, a multidisciplinary approach is beneficial for patient triage and longitudinal management.

Musculoskeletal Interventional Oncology: A Contemporary Review.

Musculoskeletal interventional oncology is an emerging field that addresses the limitations of conventional therapies for bone and soft-tissue tumors. The field's growth has been driven by evolving treatment paradigms, expanding society guidelines, mounting supportive literature, technologic advances, and cross-specialty collaboration with medical, surgical, and radiation oncology. Safe, effective, and durable pain palliation, local control, and stabilization of musculoskeletal tumors are increasingly achieved through an expanding array of contemporary minimally invasive percutaneous image-guided treatments, including ablation, osteoplasty, vertebral augmentation (with or without mechanical reinforcement via implants), osseous consolidation via percutaneous screw fixation (with or without osteoplasty), tumor embolization, and neurolysis. These interventions may be used for curative or palliative indications and can be readily combined with systemic therapies. Therapeutic approaches include the combination of different interventional oncology techniques as well as the sequential application of such techniques with other local treatments, including surgery or radiation. This article reviews the current practice of interventional oncology treatments for the management of patients with bone and soft-tissue tumors with a focus on emerging technologies and techniques.

Percutaneous Cryoablation of Plasmacytomas: Oncologic Effectiveness and Adverse Events.

PURPOSE: To evaluate the oncologic outcomes and adverse events associated with cryoablation of plasmacytomas. MATERIALS AND METHODS: Retrospective review of an institutional percutaneous ablation database showed that 43 patients underwent 46 percutaneous cryoablation procedures for treatment of 44 plasmacytomas between May 2004 and March 2021. The treatment of 25 (25 of 44, 56.8%) tumors was augmented with bone consolidation/cementoplasty. The median patient age was 64 years (interquartile range [IQR], 54-69), and 30 of 43 (69.8%) patients were men. The median maximum plasmacytoma diameter was 5.0 cm (IQR, 3.1-7.0). Thirty of 44 (68.2%) tumors were periacetabular, vertebral, or located in the iliac wing. Twenty-nine of 44 (65.9%) cryoablated plasmacytomas were recurrent tumors after prior external beam radiation therapy (EBRT). Survival analyses were performed using the Kaplan-Meier method. Adverse events were graded using Society of Interventional Radiology criteria. RESULTS: The 5-year estimated local tumor recurrence-free survival was 85.3% (95% CI, 74.1%-98.1%), the 5-year estimated new plasmacytoma-free survival was 49.9% (95% CI, 33.9%-73.4%), and the 5-year estimated overall survival was 70.4% (95% CI, 56.9%-87.1%). Nine of 46 (19.6%) major adverse events occurred in 8 patients, including 3 of 46 (6.5%) new or progressive pathologic fractures at the ablation site requiring surgical intervention, 3 of 46 (6.5%) nerve injuries, 1 of 46 (2.2%) avascular necrosis and femoral head collapse, 1 of 46 (2.2%) septic arthritis, and 1 of 46 (2.2%) acute renal failure caused by rhabdomyolysis. CONCLUSIONS: Percutaneous cryoablation is a viable treatment option for patients with plasmacytomas, including those with recurrent plasmacytomas after EBRT. Postcryoablation adverse events are relatively common.

Radiofrequency Ablation of Benign and Malignant Thyroid Nodules.

Thyroid nodule treatment has significantly evolved over recent years with attempts to individualize treatment on the basis of the cause of the nodule and patient performance status. The risks and complications associated with surgery and radioactive iodine have promoted interest in additional therapies such as radiofrequency ablation (RFA). RFA creates an electrical current through a target tissue (thyroid nodule) with resultant tissue heating causing coagulative necrosis. National and international groups are beginning to recognize the role of RFA as a viable therapeutic option in the treatment of thyroid nodules. Based on numerous guidelines, RFA is indicated in the treatment of symptomatic benign nodules and autonomously functioning nodules when surgery is refused or when the patient would not tolerate surgery. The treatment of thyroid malignancy with RFA is controversial, with some groups advocating for its use in the treatment of small papillary thyroid cancers in specific scenarios. The most important aspect of RFA is the preprocedural workup and adequate patient selection. Procedural technique varies among centers. However, RFA is typically performed as a single-day-admission outpatient procedure. Methods such as hydrodissection and a moving shot technique are employed to ensure adequate coverage of the nodule without overtreating the peripheries and damaging sensitive structures. As a result, the procedure is well tolerated, and major complications such as recurrent laryngeal nerve injury and nodule rupture are very rare. In the proper patient cohort, thyroid RFA offers an efficacious and safe option in the management of thyroid nodules. An invited commentary by Filippiadis and Vrachliotis is available online. ©RSNA, 2022.

A prospective trial of CT-guided percutaneous microwave ablation for lung tumors.

Background: Percutaneous ablation is an alternative treatment for lung cancer in non-operable patients. This is a prospective clinical trial for percutaneous microwave ablation (pMWA) of biopsy-proven lung cancer to demonstrate safety and efficacy. Methods: A prospective trial from 6-1-2016 to 1-1-2019 enrolled patients with biopsy-proven primary or metastatic lung cancer <3 cm in size and 1 cm away from the pleura for pMWA with the Emprint Ablation System with Thermosphere Technology for Phase I analysis, (Clinicaltrials.gov; #NCT0267302). Patients were followed for 1 year with PET/CT and PET/MR to determine patterns of recurrence and efficacy of ablation. Results: After 12 patients consented for biopsy, 6 patients underwent treatment of 7 lesions, 3/6 women, median age of 67 (IQR, 65-70) years, body mass index (BMI): 27.8 (IQR, 21.4-32.1) kg/m2, lesion distance to pleura 24.4 (IQR, 13-38) mm, lesion size of 10.7 (IQR, 6-14) mm, and ablation duration time 5.9 (IQR, 3-10) minutes. pMWA were completed at 75 W. Twelve adverse events were reported (1 Grade 3, 3 Grade 2, and 8 Grade 1 events) with Grade 4 or 5 events. Mean % change after ablation in forced expiratory volume in one second (FEV1) was -2% and diffusion capacity for carbon monoxide (DLCO) was -1%. After 2-3 months, the lesions would decrease in size, rim thickness, fluorodeoxyglucose (FDG) activity, and T2 signal. FDG activity after 6 months was below blood pool in all cases. The ablation zones stabilized by 6-12 months. One patient expired during the study from pneumonia unrelated to ablation without local recurrence. Of the seven ablations during the 1 year follow-up, there was local tumor recurrence at 271 days following ablation at the apex of the ablation zone, subsequently successfully treated with percutaneous cryoablation (Cryo). Conclusions: pMWA appears to be a safe and effective mechanism for treatment of primary and secondary tumors of the lung, with possible preservation of pulmonary function.

Innovative Fetal Therapy for a Giant Congenital Pulmonary Airway Malformation with Hydrops.

INTRODUCTION: Congenital pulmonary airway malformations (CPAMs) complicated by hydrops portend significant morbidity and mortality, with fetal survival estimates less than 10%. CASE PRESENTATION: We report successful use of ultrasound-guided radiofrequency ablation at 21-week gestation in a hydropic fetus with CPAM, with subsequent resolution of hydrops. Thirty-two-week MRI noted persistent mediastinal shift, and US at 36 weeks and 5 days noted polyhydramnios. Maternal gestational hypertension prompted delivery at 37 weeks, with a cesarean section performed after a failed trial of labor. The infant required CPAP at 100% and weaned to 21%. Tachypnea persisted, and chest CT on day of life 2 demonstrated multiple large cysts in the right lower lobe with anterior pneumothorax. On day of life 3, she successfully underwent a thoracoscopic right lower lobectomy. Adhesions to the chest wall and rib abnormalities were noted. She was extubated to CPAP at the conclusion of the procedure. She was able to wean to 21% on POD2 and transitioned to oral feeds. Her chest tube was removed with resultant ex vacuo pneumothorax noted. She remained asymptomatic and was discharged home on room air POD11. Pathology confirmed a type 1 CPAM. CONCLUSION: In utero radiofrequency ablation may be an adjunct to the management of large CPAM.

Bone ablations in peripheral skeleton: Rationale, techniques and evidence.

This article aims to disclose a consensus on the rationale, approaches, and the outcomes of bone ablations in the peripheral skeleton. Despite less numerous prospective studies about peripheral metastasis, interventional radiology has a role in this setting. Scrupulous attention for selection criteria, ablation technique, procedural steps, and clinical and imaging follow-up are required to provide optimal multidisciplinary care for oncologic patients.

Consensus Guidelines for the Definition of Time-to-Event End Points in Image-guided Tumor Ablation: Results of the SIO and DATECAN Initiative.

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.

Musculoskeletal Oncologic Interventions: Proceedings from the Society of Interventional Radiology and Society of Interventional Oncology Research Consensus Panel.

Musculoskeletal interventions are increasingly used with palliative and curative intent in the multidisciplinary treatment of oncology patients with bone and soft-tissue tumors. There is an unmet need for high-quality evidence to guide broader application and adoption of minimally invasive interventional technologies to treat these patients. Therefore, the Society of Interventional Radiology Foundation and the Society of Interventional Oncology collaborated to convene a research consensus panel to prioritize a research agenda addressing the gaps in the current evidence. This article summarizes the panel's proceedings and recommendations for future basic science and clinical investigation to chart the course for interventional oncology within the musculoskeletal system. Key questions that emerged addressed the effectiveness of ablation within specific patient populations, the effect of combination of ablation with radiotherapy and/or immunotherapy, and the potential of standardization of techniques, including modeling and monitoring, to improve the consistency and predictability of treatment outcomes.

Technical and safety performance of CT-guided percutaneous microwave ablation for lung tumors: an ablate and resect study.

BACKGROUND: Percutaneous image-guided thermal ablation has an increasing role in the treatment of primary and metastatic lung tumors. Achieving acceptable clinical outcomes requires better tools for pre-procedure prediction of ablation zone size and shape. METHODS: This was a prospective, non-randomized, single-arm, multicenter study conducted by Medtronic (ClinicalTrials.gov ID: NCT02323854). Subjects scheduled for resection of metastatic or primary lung nodules underwent preoperative percutaneous microwave ablation. Ablation zones as measured via CT imaging following ablation immediately and before resection surgically versus predicted ablation zones as prescribed by the investigational system software were compared. This CT scan occurred after the ablation was finished but the antenna still in position. Time (minutes) from antenna placement to removal was 23.7±13.1 (n=14); median: 21.0 (range, 6.0 to 48.0). The definition of the secondary endpoint of complete ablation was 100% non-viable tumor cells based on nicotinamide adenine dinucleotide hydrogen (NADH) staining. Safety endpoints were type, incidence, and severity of adverse events. RESULTS: Fifteen patients (mean age 58.9 years; 67% male; 33% female) were enrolled in the study, 33.3% (5/15) with previous thoracic surgery, 73% (11/15) with metastasis, and 27% (4/15) with primary lung tumors. All underwent percutaneous microwave ablation followed by surgical resection the same day. Complete ablation was detected in 54.4% (6/11), incomplete ablation in 36.4% (4/11), and delayed necrosis in 9.1% (1/11). There were no device-related adverse events. Ablation zone volume was overestimated in all patients. CONCLUSIONS: Histological complete ablation was observed in 55% of subjects. CT scanning less than an hour after ablation and tissue shrinkage may account for the smaller zone of ablation observed compared to predicted by the investigational system software.

The utility of chest computed tomography (CT) and RT-PCR screening of asymptomatic patients for SARS-CoV-2 prior to semiurgent or urgent hospital procedures.

OBJECTIVE: Presently, evidence guiding clinicians on the optimal approach to safely screen patients for coronavirus disease 2019 (COVID-19) to a nonemergent hospital procedure is scarce. In this report, we describe our experience in screening for SARS-CoV-2 prior to semiurgent and urgent hospital procedures. DESIGN: Retrospective case series. SETTING: A single tertiary-care medical center. PARTICIPANTS: Our study cohort included patients ≥18 years of age who had semiurgent or urgent hospital procedures or surgeries. METHODS: Overall, 625 patients were screened for SARS-CoV-2 using a combination of phone questionnaire (7 days prior to the anticipated procedure), RT-PCR and chest computed tomography (CT) between March 1, 2020, and April 30, 2020. RESULTS: Of the 625 patients, 520 scans (83.2%) were interpreted as normal; 1 (0.16%) had typical features of COVID-19; 18 scans (2.88%) had indeterminate features of COVID-19; and 86 (13.76%) had atypical features of COVID-19. In total, 640 RT-PCRs were performed, with 1 positive result (0.15%) in a patient with a CT scan that yielded an atypical finding. Of the 18 patients with chest CTs categorized as indeterminate, 5 underwent repeat negative RT-PCR nasopharyngeal swab 1 week after their initial swab. Also, 1 patient with a chest CT categorized as typical had a follow-up repeat negative RT-PCR, indicating that the chest CT was likely a false positive. After surgery, none of the patients developed signs or symptoms suspicious of COVID-19 that would indicate the need for a repeated RT-PCR or CT scan. CONCLUSION: In our experience, chest CT scanning did not prove provide valuable information in detecting asymptomatic cases of SARS-CoV-2 (COVID-19) in our low-prevalence population.

Trends in Musculoskeletal Ablation: Emerging Indications and Techniques.

Image-guided percutaneous thermal ablation plays an increasingly important role in the multidisciplinary management of musculoskeletal lesions. Established indications for ablation in this setting include the treatment of osteoid osteomas, palliation of painful skeletal metastases, local control of oligometastatic disease, and consolidation of bone tumors at risk for fracture. Emerging indications include the treatment of symptomatic soft tissue masses such as extra-abdominal desmoid tumors and abdominal wall endometriosis. This review will discuss considerations in patient selection and preprocedural workup, ablation technology and techniques, strategies to avoid complications, and expected outcomes of ablation in the musculoskeletal system.

Multicenter Study of Metastatic Lung Tumors Targeted by Interventional Cryoablation Evaluation (SOLSTICE).

OBJECTIVE: To assess the safety and local recurrence-free survival in patients after cryoablation for treatment of pulmonary metastases. METHODS: This multicenter, prospective, single-arm, phase 2 study included 128 patients with 224 lung metastases treated with percutaneous cryoablation, with 12 and 24 months of follow-up. The patients were enrolled on the basis of the outlined key inclusion criteria, which include one to six metastases from extrapulmonary cancers with a maximal diameter of 3.5 cm. Time to progression of the index tumor(s), metastatic disease, and overall survival rates were estimated using the Kaplan-Meier method. Complications were captured for 30 days after the procedure, and changes in performance status and quality of life were also evaluated. RESULTS: Median size of metastases was 1.0 plus or minus 0.6 cm (0.2-4.5) with a median number of tumors of 1.0 plus or minus 1.2 cm (one to six). Local recurrence-free response (local tumor efficacy) of the treated tumor was 172 of 202 (85.1%) at 12 months and 139 of 180 (77.2%) at 24 months after the initial treatment. After a second cryoablation treatment for recurrent tumor, secondary local recurrence-free response (local tumor efficacy) was 184 of 202 (91.1%) at 12 months and 152 of 180 (84.4%) at 24 months. Kaplan-Meier estimates of 12- and 24-month overall survival rates were 97.6% (95% confidence interval: 92.6-99.2) and 86.6% (95% confidence interval: 78.7-91.7), respectively. Rate of pneumothorax that required pleural catheter placement was 26% (44/169). There were eight grade 3 complication events in 169 procedures (4.7%) and one (0.6%) grade 4 event. CONCLUSION: Percutaneous cryoablation is a safe and effective treatment for pulmonary metastases.

Drivers of the Decision to Biopsy and Follow-Up of Small Suspicious Thyroid Nodules.

OBJECTIVE: In 2015, the updated American Thyroid Association (ATA) guidelines recommended observation for suspicious subcentimeter thyroid nodules, based on their indolent course. We aimed to evaluate the frequency of biopsy in suspicious thyroid nodules since the introduction of these guidelines, including factors contributing to clinical decision-making in a tertiary care center. METHODS: We conducted a retrospective study of patients in the Mayo Clinic, Rochester, Minnesota, with new, subcentimeter suspicious thyroid nodules (by report or by sonographic features) between March, 2015, and November, 2017, not previously biopsied. RESULTS: We identified 141 nodules in 129 patients: mean age 58.1±14.1 years, 74% female, 87% Caucasian. The frequency of biopsy in suspicious thyroid nodules was 39%. Ultrasound features that were the strongest predictors for biopsy on multivariate analysis included: nodule volume (odds ratio [OR] 37.3 [7.5-188.7]), radiology recommendation for biopsy (OR 2.6 [1.8-3.9]) and radiology report of the nodule as "suspicious" (OR 2.1 [1.4-3.2]). Patient's age and degree of comorbidities did not change the likelihood for biopsy, nor did it vary by clinician type or how the nodule was initially found (incidentally or not incidentally). Among 86 nodules that were not biopsied, 41% had no specific follow-up recommendations. CONCLUSION: One third of suspicious thyroid nodules underwent biopsy since the release of updated ATA guidelines. Factors driving thyroid biopsy seem to be associated with nodule characteristics but not with patient factors including age and comorbidities. Further studies and development of decision aides may be helpful in providing individualized approaches for suspicious thyroid nodules. ABBREVIATIONS: ATA = American Thyroid Association; OR = odds ratio.

Phase 1 trial of Vismodegib and Erlotinib combination in metastatic pancreatic cancer.

BACKGROUND/OBJECTIVES: Interplay between the Hedgehog (HH) and epidermal growth factor receptor (EGFR) pathways modulating the outcome of their signaling activity have been reported in various cancers including pancreatic ductal adenocarcinoma (PDAC). Therefore, simultaneous targeting of these pathways may be clinically beneficial. This Phase I study combined HH and EGFR inhibition in metastatic PDAC patients. METHODS: Combined effects of HH and EGFR inhibition using Vismodegib and Erlotinib with or without gemcitabine in metastatic solid tumors were assessed by CT. Another cohort of patients with metastatic PDAC was evaluated by FDG-PET and tumor biopsies-derived biomarkers. RESULTS: Treatment was well tolerated with the maximum tolerated dose cohort experiencing no grade 4 toxicities though 25% experienced grade 3 adverse effects. Recommended phase II dose of Vismodegib and Erlotinib were each 150 mg daily. No tumor responses were observed although 16 patients achieved stable disease for 2-7 cycles. Paired biopsy analysis before and after first cycle of therapy in PDAC patients showed reduced GLI1 mRNA, phospho-GLI1 and associated HH target genes in all cases. However, only half of the cases showed reduced levels of desmoplasia or changes in fibroblast markers. Most patients had decreased phospho-EGFR levels. CONCLUSIONS: Vismodegib and Erlotinib combination was well-tolerated although overall outcome in patients with metastatic PDAC was not significantly impacted by combination treatment. Biomarker analysis suggests direct targets inhibition without significantly affecting the stromal compartment. These findings conflict with pre-clinical mouse models, and thus warrant further investigation into how upstream inhibition of these pathways is circumvented in PDAC.

Safety and Efficacy of Percutaneous Image-guided Cryoablation of Completely Endophytic Renal Masses.

OBJECTIVE: To evaluate the safety, efficacy, and oncologic control of percutaneous image-guided cryoablation in the treatment of completely endophytic renal masses. Percutaneous image-guided cryoablation is a minimally invasive and effective treatment for small renal masses. Image-guided cryoablation is an attractive treatment for completely endophytic tumors given the challenge in visualization of such lesions during surgical extirpation. MATERIALS AND METHODS: A retrospective study evaluating percutaneous cryoablation of completely endophytic renal masses with normal overlying renal cortex was performed. From January 2003 to December 2015, 200 endophytic renal masses (RENAL score 3 - endophytic/exophytic) were identified from an internal renal ablation database. After imaging review, 49 tumors with completely intact overlying renal cortex in 47 patients were included in the study. Outcomes, including complications and oncologic efficacy were evaluated according to standard nomenclature. RESULTS: Patients comprised 37 men and 10 women (mean age 64.0 years) who underwent 48 cryoablation procedures to treat 49 renal masses. Mean tumor size was 2.5 ± 0.5 cm. Major complications occurred following 5 of the 48 (10%) procedures. Forty of 46 (87%) tumors with imaging follow-up were recurrence-free at a mean of 56 months. Five of six local recurrences were successfully retreated with cryoablatoin. CONCLUSION: Percutaneous thermal ablation of completely endophytic renal masses is a relatively safe procedure associated with acceptable complication and local tumor control rates. Given the complexities associated with partial nephrectomy, percutaneous cryoablation may be considered an alternative treatment for these select patients. Long-term follow-up studies are necessary to determine the durable efficacy of this treatment.

Single-Dose Neoadjuvant AKT Pathway Inhibitor Reduces Growth of Hepatocellular Carcinoma after Laser Thermal Ablation in Small-Animal Model.

BackgroundLocal recurrence following thermal ablation of hepatocellular carcinoma (HCC) larger than 2-3 cm remains a challenging clinical problem. Prior studies suggest that phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR)-dependent protein kinase B (AKT) signaling mediates HCC cell survival caused by moderate heat stress in vitro, but these findings need in vivo validation.PurposeTo test the hypothesis that neoadjuvant inhibition of PI3K/mTOR/AKT signaling reduces HCC tumor growth in vivo after laser ablation and to evaluate the effects of moderate heat stress on molecular signaling and cellular function in HCC cells in vitro.Materials and MethodsHCC tumor-bearing mice were randomized to neoadjuvant PI3K/mTOR inhibitor (BEZ235) or control groups followed by an intentional partial laser ablation or sham ablation; there were at least nine mice per group. Postablation tumor growth was monitored up to 7 days. Tumor volumes were compared for drug or ablation groups by using two-way analysis of variance. N1S1 HCC cells pretreated with BEZ235 or control and subjected to moderate heat stress (45°C for 10 minutes) or control (37°C for 10 minutes) were analyzed by using mass spectrometry. Protein interaction networks were derived from protein expression analysis software, and cellular function activation state (Z-score) and fold-change in AKT phosphorylation were calculated.ResultsThere was a 37%-75% reduction in HCC tumor volume by day 7 after ablation in the BEZ235 plus ablation group (713 mm3 ± 417) compared with vehicle plus sham (1559 mm3 ± 552), vehicle plus ablation (1041 mm3 ± 591), and BEZ235 plus sham (1108 mm3 ± 523) groups (P < .001, P = .04, and P = .005, respectively). PI3K/mTOR inhibition prevented moderate heat stress-induced AKT signaling (Z-score, -0.2; P < .001) and isoform-specific AKT phosphorylation compared with the vehicle plus heat stress group. PI3K/mTOR inhibition prevented moderate heat stress-induced global effects on HCC molecular signaling and cellular function, including decreased cell survival, growth, and proliferation (Z-score, -0.3 to -3.2; P < .001) and increased apoptosis and cell death (Z-score, 0.4-1.1; P < .001).ConclusionModerate heat stress induces PI3K/mTOR/AKT-dependent global effects on hepatocellular carcinoma (HCC) cell survival, function, and death. Neoadjuvant PI3K/mTOR/AKT inhibition reduces postablation HCC tumor growth.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by White in this issue.