Percutaneous Image-Guided Core Needle Biopsy of Neuroendocrine Tumors: How Common Is Intraprocedural Carcinoid Crisis?

Clinical question
What is the incidence of carcinoid crisis, physiologic disturbances, and other complications during percutaneous image-guided core needle biopsy of neuroendocrine tumors (NETs) in the lung and the liver?

Take away point
Percutaneous image-guided core biopsy of NETs is quite safe, with very low complication rate and no definite carcinoid crisis within the current small cohort.

Reference
Percutaneous Image-Guided Core Needle Biopsy of Neuroendocrine Tumors: How Common Is Intraprocedural Carcinoid Crisis? Jang, Samuel et al. Journal of Vascular and Interventional Radiology, Volume 32, Issue 5, 2021, Pages 745-751.

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Study design
Single-center retrospective (10 years) cohort study, including 106 biopsies from 16 patients with pathology proven diagnosis of carcinoid or NET.

Funding Source
Self-funded or unfunded.

Setting
Mayo Clinic Department of Radiology, Rochester, Minnesota

Figure

Figures: (Left) Percutaneous CT-guided biopsy of a 2.3-cm lesion in the right upper lobe. Histopathologic diagnosis was ‟typical carcinoid tumor.” (Right) Percutaneous US-guided biopsy of a 3.0-cm lesion with a hypoechoic rim in the peripheral posterior right hepatic lobe. Histopathologic diagnosis was ‟well-differentiated neuroendocrine tumor.”

Summary

Neuroendocrine tumors (NETs) can produce vasoactive hormones that cause a range of physiologic events which are collectively known as carcinoid syndrome. It predominantly occurs in serotonin-producing tumors of the small intestine and patients with hepatic metastasis. A potential life-threatening complication of carcinoid syndrome is carcinoid crisis, caused by the sudden massive release of vasoactive substances that precipitate physiologic crisis, triggered by interventions and manipulation of these tumors. Incidence of carcinoid crisis has been studied in multiple therapeutic procedures, however, no retrospective cohort studies that examine the rate of adverse physiologic effects from image-guided percutaneous biopsy of NETs have been completed.

Retrospectively 106 computed tomography (CT) or ultrasound (US)-guided core needle biopsies of lung and liver NETs from 95 patients were reviewed over a 10 year period (Jan 2010 to Jan 2020). Patients’ mean age was 64 ± 13 years, and 48% were female. Small bowel primary site was the most common (33%). Most patients had widely metastatic disease, while only 32 patients (34%) had fewer than 5 lesions at the time of biopsy. Thirty two (34%) patients had pre-existing symptoms of carcinoid syndrome, the most common symptom being diarrhea (88%). The mean tumor size was 3.2 ± 2.6 cm, and mean number of passes was 3.4 ± 1.6. A 17/18-gauge needle was used in 91% of the biopsies. Thirteen (12%) patients received either outpatient or prophylactic octreotide. Patients’ malignancies were deemed functional or nonfunctional based on clinical documentation determined by the patients’ oncologist 30 day prior to biopsy, of which 36% of the tumors were deemed functional. Neuroendocrine markers including were available for Potential physiological disturbances related to the biopsies were analyzed based on nursing documentation noting the exact times of the biopsies, and individual patients’ oxygen saturation, heart rate, blood pressure, and respiratory rate immediately prior to the first tumor passage and just after the last passage.

Carcinoid crisis as it was defined in the study was not encountered in the studied cohort. One major complication and four minor complications were encountered. Paired t test was used to compare pre and post biopsy physiological data, of which no statistically significant change was observed, even in multiple subgroup analysis of patients with proposed risk factors. Mean and standard deviation were used for continuous variables, and frequency counts with percentages were used for categorical variables. No previous studies of NET biopsy described carcinoid crisis as a complication. Taken in context with the current study, the authors conclude carcinoid crisis from core biopsy is extremely rare (only 4 case reports), and percutaneous image-guided biopsy of NETs can likely be performed without prophylactic octreotide administration.

Commentary

The authors acknowledge study limitations, including limitations of their statistical analysis due to the low number of complications, no standard panel of pre-procedure neuroendocrine markers for each patient, and the subjective nature of documenting pre-existing carcinoid crisis based on EMR documentation. However, I believe this study was well-performed and legitimate for a single center retrospective cohort, especially considering the rarity of NET and a10-year time frame. The study is unique in that it is the only study to analyze intraprocedural physiologic data in the context of biopsy of NETs, showing no statistically significant change from pre- to post-biopsy, even in subgroup analysis.

I agree with the authors' clinically significant conclusions, and think they have future implications in guiding proceduralists' approach to biopsy of NETs. The authors make a strong case that carcinoid crisis in percutaneous biopsy of NET is extremely rare, in presenting both the current study and other similar biopsy studies of NET. They also conclude prophylactic octreotide administration prior to percutaneous biopsy is likely not necessary regardless of tumor burden, tumor functional status, and neuroendocrine markers. The authors contextualize this conclusion in saying that the proceduralist should remain vigilant of carcinoid crisis and prepared to respond swiftly.

Post Author
Gregory Rufener, MD
Radiology Resident (PGY-4)
Department of Diagnostic Radiology
Oregon Health and Science University, Portland, Oregon
Twitter: @gregoryrufener

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Effectiveness of Thermal Ablation and Stereotactic Radiotherapy Based on Stage I Lung Cancer Histology

Clinical question
Is there a difference in effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) as initial treatments for stage I lung cancer depending on histologic subtypes?

Take away point
Overall survival following TA and SBRT for stage I lung cancer is comparable for most histologic subtypes, except for non-small cell neuroendocrine tumors (NETs), where overall survival is higher after TA.

Reference
Uhlig J, Mehta S, Dendy Case M, Dhanasopon A, Blasberg J Homer R, Solomon S, Kim H. Effectiveness of Thermal Ablation and Stereotactic Body Radiotherapy Based on Stage I Lung Cancer Histology. J Vasc Interv Radiol. 2021; 32:1022-1028. doi.org/10.1016/j.jvir.2021.02.025

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Study design
Retrospective, database analysis using 2004-2016 data from the National Cancer Database.

Funding Source
No reported funding.

Setting
National database study via the National Cancer Database; USA.

Figure



The effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) according to histologic lung cancer subtypes.

Summary

Histologic subtypes of lung cancer are known to affect initial treatment and prognosis. In patients who are not surgical candidates or who have an unfavorable comorbidity profile for chemotherapy, thermal ablation (TA) or stereotactic body radiotherapy (SBRT) are options, but comparative effectiveness data is lacking. The authors perform a retrospective database analysis comparing effectiveness of TA and SBRT based on histologic subtype for initial treatment of stage I lung cancer.

The National Cancer Database was queried for patients having undergone initial treatment for stage 1 lung cancer with TA or SBRT from 2004-2016. Patients were excluded if they were <18 years of age, received surgery or chemotherapy, had unknown survival or follow up, or had a lung cancer histologic subtype that did not fall under the 2015 World Health Organization (WHO) classification system. The Charleston Comorbidity Index (CMI) was used to stratify comorbidities.

Primary outcome was overall survival defined as time from treatment until patient death or censoring. Initial data were evaluated and nearest-neighbor propensity score matching was completed with a 1:5 ratio of patients receiving TA versus SBRT. Propensity score matching was verified with a Kolmogorov-Smirnov test.

A total of 28,425 patients met criteria with 947 having undergone TA and 27, 478 having undergone SBRT. Propensity score matching was completed using the aforementioned variables identified in the multivariable logistic regression. Matched cohorts included 817 patients receiving TA and 4,085 patients receiving SBRT. Subgroup analyses were stratified according to histologic subtype as defined by the WHO 2015 classification system and included adenocarcinoma, non-NET large cell carcinoma, small cell carcinoma, non-small cell NET, and squamous cell carcinoma. Overall survival curves were generated via Cox regression and hazards ratios were calculated.

From initial analyses using the full nonmatched cohorts, TA was independently associated with Caucasian race, a greater number of comorbidities, earlier year of cancer diagnosis, smaller tumor diameter, tumor location in the lower lobe, facility location in the Middle Atlantic or New England regions, and tumor subtype of non-small cell NETs.

There was no significant difference in overall survival between TA and SBRT overall (HR=1.07, p=.13). In the subgroup analysis, OS was significantly longer for TA versus SBRT in patients with non-small cell NETs (HR=0.48, p=.04). There was no statistically significant difference in OS in the other histologic type subgroups [adenocarcinoma (HR=1.08, p=.20), non-NET large cell carcinoma (HR=2.12, p=.25), small cell carcinoma (HR=.93, p=.82), and squamous cell carcinoma (HR=1.12, p=.12)].

The authors discuss why TA may be more effective in non-small cell NETs. NETs are often well-defined, smaller diameter, and thus a better target for TA than other subtypes. Additionally, NETs are known to be less aggressive than other subtypes and are comparatively radioresistant.

While SBRT is considered the standard of care in patients with NSCLC and less invasive than TA, it often incurs longer lasting complications such as fatigue, pneumonitis, and chest wall pain. In comparison, TA has known risks of pneumothorax and pleural effusion, but can be completed on a single session, which is more convenient for the patient and more cost effective.

Commentary

The authors evaluate the effectiveness of TA versus SBRT as initial treatment for patients with stage I lung cancer among histologic subtypes using data from the National Cancer Database. Several limitations exist, most inherent to the database design. Data on combination or repeat/salvage treatment, details of procedural complications, and cancer-specific recurrence were not available. This precluded evaluation of complication rate, as well as limits the overall specificity of the conclusions. Additionally, lack of technical details (such as probe count and type of ablation) limit further comparison between TA and SBRT. Lastly, there are intrinsic limitations to a retrospective study design with propensity score matching; a prospective, randomized trial would certainly be a more robust evaluation.

The main advantage of this study is the large-scale nature allowing for ample power and improved reliability of the primary endpoint that showed increased OS in patients with non-small cell NETs receiving TA versus SBRT. Interestingly, the non-small cell NET subtype was independently associated with TA, suggesting that providers may already more strongly favor TA as initial treatment in this subgroup.

The authors also offer commentary on their results regarding the demographic factors associated with TA. Despite broad results showing comparable effectiveness of TA and SBRT, TA is disproportionally utilized in the northeastern US and in Caucasian patients. The authors hypothesize this may be related to differences in socioeconomic status, insurance status, or comorbidity profile, highlighting known healthcare disparities in the US. A lack of provider awareness of TA may also contribute to this distribution.

While intrinsically limited, this large-scale study still offers a valuable insight into the effectiveness of TA and SBRT in treating the histologic subtypes of stage I lung cancer and suggests considering TA over SBRT as initial treatment in nonsurgical patients with stage I non-small cell NETs. This study also raises awareness of TA as an effective alternative treatment for stage I lung cancer in the appropriate clinical setting.

Post Author
Catherine (Rin) Panick, MD
Resident Physician, Integrated Interventional Radiology
Dotter Interventional Institute
Oregon Health & Science University
@MdPanick

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Contemporary Management of Pediatric Blunt Splenic Trauma: A National Trauma Databank Analysis

Clinical question
In pediatric patients with blunt splenic injury, what are the treatment outcomes and utilization of non-operative management (NOM), splenic artery embolization (SAE), splenic repair and splenectomy?

Take-away point
NOM is a common first-line therapy for all splenic injury grades with low failure rate in appropriate patients. If intervention is needed, SAE is effective and increasingly utilized.

Reference
Shinn, K., et al., Contemporary Management of Pediatric Blunt Splenic Trauma: A National Trauma Databank Analysis. Journal of Vascular and Interventional Radiology, 2021. 32(5): p. 692-702

Click here for abstract

Study Design
Retrospective review

Funding Source
Emory University Department of Emergency Radiology and Interventional Radiology, who purchased access to the National Trauma Data Bank.

Setting
Multi-center self-reported entry into National Trauma Data Bank (NTDB) maintained by the American College of Surgeons (ACS).

Figure

Summary

Isolated splenic injury accounts for 48-60% of all pediatric blunt abdominal traumas. Splenic injury management has dramatically changed from splenectomy to non-operative management in more than 90% of cases. Non-Operative Management (NOM) is defined as conservative management without associated intervention (e.g. surgery, embolization, etc.). In the adult population, SAE plays a key role in the treatment of acute traumatic injury, however data in pediatric population is scarce.

Using the NTDB, from 2007 – 2015 pediatric patients with splenic injury were identified and 24,128 met inclusion criteria. Patients were grouped based on management techniques including NOM, splenectomy, splenic repair, interventional radiology procedures (angiography or embolization), or a combination therapy. Patients were considered failed NOM if splenectomy or embolization more than 24 hours after hospitalization occurred. Similarly, SAE failure was defined as surgical intervention after SAE in the first 24 hours of admission. Failed NOM occurred in 1.5% (180/12,378) of patients and was associated with increased splenic injury severity. Of all SAE patients, 1.3% (6/456) failed; however, the embolization failure rate was 0% in lower severity splenic injury grades (I/II). In higher severity (grade V) splenic injuries, embolization failure was up to 33.3% (1/3). NOM was independently associated with a decreased mortality rate when compared to splenectomy (OR: 0.1, P<0.001) and combination therapy (OR: 0.09, P< 0.001). SAE was associated with a lower mortality rate compared to splenectomy (OR: 0.1, P< .001) and combination therapy (OR: 0.009, P<.001). No statistically significant mortality difference was seen between SAE and NOM (OR 0.96, P=1). After controlling for age, gender, baseline systolic blood pressure, type of facility and grade of splenic injury, NOM had the lowest mortality rate, followed by SAE and finally by splenectomy or combination therapy.

The authors concluded that NOM is appropriate therapy for pediatric splenic injury meeting inclusion criteria. In addition, NOM demonstrated improved clinical outcomes including LOS and few ICU days. Adjusted data demonstrated that SAE resulted in decreased morbidity and mortality when compared to splenectomy. The rate of failure of embolization in clinical practice was found to be very low, with only 1.3% of the cohort requiring a subsequent splenectomy.

Commentary

This review demonstrates the high success rate for NOM and the increasing utilization of SAE over splenectomy in pediatric patients with traumatic splenic injury. If using the American Association for Surgery of Trauma Organ Injury Scale splenic injury grade, this review suggests that grade I and II injuries that fail NOM should be treated with SAE as embolization failure rate was 0%. Grade V injuries treated with SAE (n=3) demonstrated a 33.3% failure rate (1/3), however the overall failure rate (1.3%) and lower mortality rate of SAE compared to splenectomy or combination therapy suggests that the less invasive nature may be warranted as a first option for higher grade injuries.

Limitations of the review is the nature of the NTDB as a self-reported registry, with limited data regarding 30-day survival, as well as long term follow to determine associated complication rates of the management options. The variable availability of SAE as a treatment at the included centers is another confounding variable.

Post Author
Anel Yakupovich, MD
Integrated Vascular & Interventional Radiology Residency, Class of 2024
Rush University Medical Center

David M. Tabriz, MD
Assistant Professor
Rush University Medical Center
@DrDaveTabriz

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Predictive Value of Preprocedural Computed Tomography Angiography for the Technical Success of Transarterial Embolization of Type II Endoleaks Arising from the Lumbar Arteries

Clinical question
Can preprocedural computed tomography angiography (CTA) predict treatment success of transarterial embolization in patients with Type II endoleaks fed by lumbar arteries?

Take-away point
Presence of a traceable path of the feeding lumbar/iliolumbar artery on preprocedural CTA is associated with increased rates of technical success.

Reference
Contrella, B., Wilkins, L., Sheeran, D., et al. Predictive value of preprocedural computed tomography angiography for the technical success of transarterial embolization of type II endoleaks arising from the lumbar arteries. Journal of Vascular and Interventional Radiology. 2021;32(7):1016-1021.

Click here for abstract

Study design
Retrospective cohort study

Funding source
Self-funded or unfunded

Setting
Single institution, University of Virginia, Charlottesville, VA

Figure

Figure. Computed tomography angiography (CTA) maximum intensity projection images in oblique sagittal (a) and oblique axial (b) planes demonstrated opacified arterial collateral vessels (white arrows) extending from the aneurysm sac to the iliolumbar artery. (c) Digital subtraction angiogram with a flush catheter in the aorta during subsequent transarterial treatment demonstrated an opacified path (black arrow) extending from the internal iliac artery to the aneurysm sac, corresponding with prior CTA. (d) Technically successful passage of a microcatheter into the aneurysm sac, with location confirmed using contrast medium injection. Sac embolization was subsequently performed using coils and ethylene vinyl alcohol copolymer.

Summary

Type II endoleak, the most common type to occur after endovascular aneurysm repair (EVAR), occurs in 8-30% of patients who undergo the procedure based on post-procedural surveillance imaging. While most spontaneously resolve on further follow-up, some warrant treatment (e.g. persistence, increased aneurysm size). These endoleaks are often treated either by embolizing the feeder vessel, which most commonly arises from lumbar arteries or the inferior mesenteric artery (IMA), or by direct puncture and embolization of the aneurysm sac itself, via either translumbar or transcaval routes. The procedure of choice is usually determined by a combination of CTA imaging, prior interventions, and operator preference, as there is little data to support one method over the other. Additionally, 17-24% of treated type II endoleaks require multiple procedures to achieve technical and clinical success.

In this retrospective cohort study, all patients who underwent endovascular embolization for type II endoleak due to a lumbar artery feeder over a 9.5-year period were analyzed. Inclusion required a post-EVAR CTA demonstrating the endoleak. Patients who ultimately underwent translumbar or transcaval sac embolization during the first embolization procedure or subsequently were included. Patients with feeding vessels arising from the IMA were excluded. For each patient, post-EVAR CTA imaging was reviewed by 2 interventional radiologists. The presence or absence of a feeding vessel with continuous traceability between the source lumbar artery to the aneurysm sac was determined. Discrepancies in traceability were reviewed by a third interventional radiologist. All image reviewers were blinded to eventual procedure outcome.

57 procedures were analyzed in 54 patients. These procedures were categorized as either traceable (18, 32%) or non-traceable (39, 68%). Patient demographics, anticoagulation, comorbidities including DM, HTN, COPD, malignancy or CAD, as well as history of previous vascular surgery all did not differ between groups. Technical success was defined as microcatheter passage into the aneurysm sac with subsequent use of a liquid embolic to embolize the aneurysm sac. Technical success was achieved in 16 (89%) of the patients with feeder vessel traceability on CTA and in 10 (26%) of those in the non-traceable group (p < 0.001). In the 31 cases that were not successful using transarterial embolization, patients were treated with percutaneous aneurysm sac puncture (17, 55%), embolization of the endoleak nidus through the arc of Riolan to the IMA (5, 16%), transcaval aneurysm sac puncture (2, 6%), additional endograft placement (1, 3%), or active surveillance (6, 19%).

In 6 of the 57 cases (11%), a type I or type III endoleak were found on angiography in addition to the type II endoleak. These were all treated either during the same procedure or during subsequent procedures. 1 major complication occurred in the traceable group and 2 occurred in the non-traceable group (p = 0.88). No minor complications occurred in the traceable group and 1 occurred in the non-traceable group (p = 0.46). Major complications included a femoral artery pseudoaneurysm, brachial artery pseudoaneurysm, and hemorrhagic stroke. The single minor complication was post-procedural nausea requiring overnight admission.

Commentary

This study demonstrated relatively high rate of technical success in transarterial treatment of lumbar-fed type II endoleaks in patients with a traceable feeding vessel on pre-procedural CTA. The investigators claim a paucity of previous data establishing superiority between transarterial embolization or direct sac puncture for treating type II endoleak. The investigation has several limitations, including variability in CTA quality. The authors astutely point out the possibility of false negatives resulting from otherwise traceable feeding vessels being missed due to lower image quality. There is also the issue of variability in technique and tools used for vessel catheterization and embolization. This study did not statistically analyze differences between groups to evaluate for differences in techniques and tools that may have confounded the rate of technical success between groups. Lastly, the overall technical success of all procedures (46%) was lower than previous studies. This may be explained by the initial default to transarterial approach instead of an aortogram followed by interventionalist discretion as done in other investigations. 

Given the significant result of improved technical success with traceability on CTA, further investigations should be expanded to similar analysis regarding feeding vessels from the IMA. A larger retrospective trial that further evaluates the utility of traceability with more uniform CTA study quality would be a promising next step in resolving a blind spot in the evidence, helping to assist interventionalists in procedure selection for this common problem.

Post Author
Jared Edwards, MD
General Medical Officer
Medical Readiness Division
Naval Surface Forces Pacific, San Diego, CA
@JaredRayEdwards

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Yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Invasion: Validation of the Milan Prognostic Score

Clinical question
Does the Milan portal vein tumor thrombosis (PVTT) score represent a useful tool in selecting patients with hepatocellular carcinoma (HCC) with PVTT who may benefit from radioembolization?

Take away point
This study supports the use of the Milan PVTT score as a clinical tool to identify subgroups of patients with HCC and concurrent PVTT who may benefit most from transarterial radioembolization (TARE), demonstrating an overall survival (OS) of greater than 2 years in the properly selected patient.

Reference
Yttrium-90 Radioembolization for Hepatocellular Carcinoma with Portal Vein Invasion: Validation of the Milan Prognostic Score. Bargellini, Irene et al. Journal of Vascular and Interventional Radiology, Volume 31, Issue 12, 2028 - 2032

Click here for abstract

Study design
Retrospective single-center cohort study including 70 patients with advanced HCC and PVTT.

Funding Source
Self-funded or unfunded

Setting
Academic hospital, Pisa University Hospital, Pisa, Italy.

Figure

Figure: OS according to Milan PVTT prognostic scores: group A, good prognosis; group B, intermediate prognosis; group C, dismal prognosis.

Summary

Although advanced-stage HCC is traditionally treated by systemic therapies, there is ongoing debate about the role of locoregional therapies for these patients, in particular those with PVTT. To date, prospective randomized trials have not demonstrated an advantage of TARE versus sorafenib systemic therapy in intermediate to advanced stage HCC. The Milan PVTT score has been recently proposed as a stratification model to better predict outcomes in those with advanced HCC and PVTT undergoing yttrium-90 (Y90) TARE; three parameters including bilirubin levels, extent of PVTT extension, and tumor burden delineate 3 subgroups with good, intermediate, and poor prognosis. As previously described, using this model to select Y90 TARE candidates with good liver function and limited PVTT showed a median OS time as long as 30 months. This study was undertaken using a slightly modified Milan PVTT score, in an effort to further validate the stratification model.

Patients with advanced HCC and PVTT were selected based on the following criteria; presence of HCC with PVTT diagnosed according to the European Association for the Study of the Liver criteria, PVTT extending to the main portal trunk but not exceeding the level of the hepatic hilum, absence of extrahepatic metastases, Child-Pugh class/score no worse than B/7, Easter Cooperative Oncology Group (ECOG) performance status 0/1, and age > 18 years. A total of 70 patients were included, some of which had previous locoregion, surgical, or systemic HCC treatment.

PVTT was defined as visualized filling defects in the portal venous phase with enhancement during the arterial phase. PVTT was graded as segmentary (PV1, score of 0), second-order venous branch (PV2, score of 2), first-order branch (PV3, score of 3), and main portal trunk (PV4, score of 4). Patients were stratified using a Milan PVTT score modified to include PV4. Additionally, PVTT score was summed with bilirubin level (≤ 1.2 mg/dL [score of 0], > 1.2 mg/dL [score of 2]), and tumor burden (≤ 50% [score of 0], >50% [score of 3]) to grade patients into a good prognosis (total score of 0), intermediate prognosis (total score of 2 or 3), and poor prognosis (total score > 3). Fifteen patients (21.4%) were in the good prognostic group, 33 (47.1%) in the intermediate prognostic group, and 22 (31.4%) in the poor prognostic group.

TARE was preceded by a standard simulation procedure using technetium-99m–labeled macroaggregated albumin to map arterial feeding vessels and characterize shunting to nontarget organs. Both Y90 resin (SIR-Sphere, used in 64.3% of patients) and glass (TheraSphere, used in 35.7% of patients) were administered by 2 interventional radiologists. Followup included triphasic CT and/or magnetic resonance imaging with routine clinical and laboratory follow-up every 4-6 weeks, followed by every 3 months thereafter. Tumor response was based on a modified Response Evaluation Criteria in Solid Tumors, defined as complete response, progressive disease (PD) in unequivocal progression, and non-PD in all other patients. Data was analyzed using the mean and standard deviation compared with χ2 or Fisher exact tests for categorical data and Student t test for paired data. OS and progression-free survival were calculated using the Kaplan–Meier method, and survival curves were compared by log-rank test.

Median OS was significantly (P = 0.0012) different according to modified Milan PVTT score: 24.6 months in the good prognosis group, 13 months in the intermediate prognosis group (hazard ratio, 3.2; 95% CI, 1.2–9.7; P = 0.016), and 5.9 months in the poor prognosis group (hazard ratio, 4.1; 95% CI, 1.4–13.4; P = 0.0096; See Fig). Complete response was found in 3 cases (4.5%), partial response in 33 cases (50%), stable disease in 21 cases (31.8%), and PD in 9 cases (13.6%). The early objective tumor response rate and median progression-free survival were not significantly different across prognostic groups. In the case of PD or residual viable tumor, patients were treated according to disease presentation after multidisciplinary tumor board discussion. Treatment included additional TARE, chemoembolization, percutaneous ethanol injection, systemic therapy, or second-line experimental systemic therapies.

Overall, the authors think their results externally validate the previously created Milan PVTT score. The authors directly compare their results to multiple similar studies which reported similar OS stratification. The score allows easy grouping of patients with advanced-stage HCC with PVTT who could most benefit from radioembolization.

Commentary

The authors identify some key limitations inherent to their retrospective study, including possible selection bias in patients selected for radioembolization after multidisciplinary discussion, heterogeneous patient clinical history and previous treatment, the two types of spheres used for TARE, and variable follow-up treatment used to treat residual tumor or control tumor progression. I agree that the heterogeneity of the patients and their follow-up treatment planning certainly limits the scope of the study.

Ultimately, this study serves to validate and slightly modify the Milan PVTT model, but has little clinical significance in and of itself. The authors astutely identify that this model could represent the basis for future studies comparing locoregional approaches such as TARE versus systemic therapies, as well as evaluating future therapeutic combinations. This simple model can serve as a foundation for future integration of additional tumor data, such as pathology, genomics, and derived radiomics, contributing to increasingly sophisticated means of stratifying patients for various treatments.

Post Author
Gregory Rufener, MD
Radiology Resident (PGY-3)
Department of Radiology
Oregon Health and Science University, Portland, Oregon
Twitter: @gregoryrufener

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