Long-term Outcome Comparison of 2 Techniques for Embolization of Splenic Artery Aneurysms.

PURPOSE: The aim of the study is to analyze our single-center experience in endovascular treatment of splenic artery aneurysms (SAAs) with transcatheter coil embolization, comparing long-term outcomes of packing and sandwich techniques. MATERIALS AND METHODS: Between January 2010 and December 2021, 28 patients with certain diagnosis of non-ruptured asymptomatic SAA were treated with 2 different embolization techniques (packing, n=10, and sandwich, n=18). Early outcomes assessed were technical success, overall mortality, mean hospital stay, post-embolization syndrome rate, and freedom from splenectomy rate. Estimated 5-year outcomes in terms of freedom from sac reperfusion, and freedom from reintervention were evaluated and compared between the 2 different embolization techniques. RESULTS: The mean SAA diameter was 2.8±0.8 cm. Overall technical success rate was 100%. Intraoperative and 30-day mortality rates were 0 in both groups. One patient in the sandwich group required a postoperative splenectomy. The mean follow-up period was 58.3±44.5 months. Estimated overall 5-year survival was 86.7%. Five-year freedom from sac reperfusion was 100% in the sandwich group, and 85.7% in the packing group, with no difference between the 2 groups (p=0.131), whereas freedom from reintervention was 100% in the sandwich group, and 75% in the packing group with a statistically significant difference (p=0.049; log-rank=3.750). CONCLUSIONS: Embolization of SAAs seemed to be safe and effective with 100% of technical success rate and good perioperative results. Both sandwich and packing techniques yielded promising results also in the long-term period. CLINICAL IMPACT: Transcatheter coil embolization of splenic artery aneurysms seems to be a safe and effective procedure with a 100% technical success and satisfactory perioperative outcomes. Sandwich and packing techniques offer good results in the long-term period. Freedom from reintervention seems to be optimal and comparable between the 2 techniques.

Guidelines on the diagnosis, treatment and management of visceral and renal arteries aneurysms: a joint assessment by the Italian Societies of Vascular and Endovascular Surgery (SICVE) and Medical and Interventional Radiology (SIRM).

The objective of these Guidelines is to provide recommendations for the classification, indication, treatment and management of patients suffering from aneurysmal pathology of the visceral and renal arteries. The methodology applied was the GRADE-SIGN version, and followed the instructions of the AGREE quality of reporting checklist. Clinical questions, structured according to the PICO (Population, Intervention, Comparator, Outcome) model, were formulated, and systematic literature reviews were carried out according to them. Selected articles were evaluated through specific methodological checklists. Considered Judgments were compiled for each clinical question in which the characteristics of the body of available evidence were evaluated in order to establish recommendations. Overall, 79 clinical practice recommendations were proposed. Indications for treatment and therapeutic options were discussed for each arterial district, as well as follow-up and medical management, in both candidate patients for conservative therapy and patients who underwent treatment. The recommendations provided by these guidelines simplify and improve decision-making processes and diagnostic-therapeutic pathways of patients with visceral and renal arteries aneurysms. Their widespread use is recommended.

Thermal ablation of hepatocellular carcinoma.

Percutaneous treatment of hepatocellular carcinoma (HCC) by means of thermal ablation (TA) has been introduced in clinical guidelines as a potentially curative treatment for the early stages of the disease since the early 2000s. Due to its safety profile and cost-effectiveness, TA can be offered as a first-line treatment for patients with HCC smaller than 3 cm. Thermal ablative techniques are in fact widely available at many centres worldwide and include radiofrequency (RF) and microwave (MW) ablation, with the latter increasingly applied in clinical practice in the last decade. Pre-clinical studies highlighted, as potential advantages of MW-based ablation, the ability to achieve higher temperatures (>100°C) and larger ablation zones in shorter times, with less susceptibility to blood flow-induced heat sink effects. Despite these advantages, there is no evidence of superior overall survival in patients treated with MW as compared to those treated with RF ablation. Local control has been proven to be superior to MW ablation with a similar complication rate. It is expected that further improvement of TA results in the treatment of HCC will result from the refinement of guidance and monitoring tools and the careful assessment of ablation margins. Thermal ablative treatments may also be performed on nodules larger than 3 cm by applying multiple devices or combining percutaneous and intra-arterial approaches. The role of novel immunotherapy regimens in combination with ablation is also currently under evaluation in clinical trials, with several potential benefits. In this review, indications, technical principles, results, and future prospects of TA for the treatment of HCC will be examined.

Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma.

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC.

Role of Transhepatic Arterial Radioembolization in Metastatic Colorectal Cancer.

The liver represents the most frequent location of metastatic disease in colorectal cancer (CRC). In oligometastatic disease, while surgery remains the mainstay of treatment, loco-regional therapies allow to locally control tumor progression and prolong survival. There is consensus in the use of transhepatic arterial radioembolization (TARE) in metastatic CRC chemorefractory patients, with liver-only or liver-dominant disease. Beyond this indication, TARE may be considered in other clinical scenarios, such as in the second-line combined with chemotherapy, as a bridge in between different lines of systemic therapies, and as ablative technique under specific circumstances. This paper outlines the current evidence for TARE in mCRC and presents possible future indications and directions.

An unusual cause of failure in Zenith Alpha Abdominal endograft.

BACKGROUND: Graft disruption is an unusual complication of the endovascular abdominal aortic aneurysm repair (EVAR). CASE PRESENTATION: A 71-year-old man underwent standard EVAR with Zenith Alpha Abdominal endograft. Follow-up examinations revealed an initial significant sac shrinkage. At 24 months, duplex ultrasound (DUS) scan and computed tomography showed increase of the sac diameter associated with complete disconnection of the suprarenal stent-graft from the main body without evidence of endoleak. A standard relining with a thoracic endograft was performed between the suprarenal stent and the main body of the previous graft. At 6 months DUS revealed sac shrinkage. CONCLUSIONS: This report demonstrates an uncommon cause of endograft failure with suprarenal stent disconnection from main body and highlights the need for continuous follow-up in patients undergoing EVAR.

Predicting the coagulation volume induced by microwave ablation of hepatocellular carcinoma: the role of deposited energy, ex-vivo bovine liver charts and central hyperdense area on post-treatment CT.

PURPOSE: To study the correlation between the overall coagulation zone (A) attained in percutaneous microwave ablation (MWA) of hepatocellular carcinomas (HCC) and: (1) the hyperdense zone (C) visible in the central part of zone A on post-treatment unenhanced CT scans; (2) the deposited energy; (3) the coagulation zones observed on ex-vivo bovine liver. MATERIALS AND METHODS: The post-procedural computed tomography (CT) scans of HCCs treated with a single energy deployment through the same 2450 MHz MWA system were retrospectively analyzed, retrieving the dimensions of A and C zones and the deposited energy (E). Ex-vivo bovine liver MWA with the same system were performed and analyzed to determine the same quantities by gross-pathologic examination and CT imaging. RESULTS: A total of 101 HCC treatments were analyzed. The average coagulation volumes increased linearly with deposited energy (1.11 cc/kJ, R2 = 0.90, 4.2 kJ ≤ E ≤ 48 kJ), similarly to ex-vivo findings (1.38 cc/kJ, R2 =0.97, 7.2 kJ ≤ E ≤ 144 kJ). The long axis (L) and short axis (D) of zones A and C held a fairly constant ratio both in-vivo (LC/LA=0.43 ± 0.13; DC/DA=0.42 ± 0.10) and ex-vivo (LC/LA = 0.49 ± 0.07; DC/DA = 0.28 ± 0.06). CONCLUSIONS: The average dimensions of the ablation zone induced by the considered system on HCC increase linearly with the deposited energy and are fairly well predicted by the corresponding ex-vivo dimensions. The ratio between each linear dimension of A and C zones was found to be roughly constant over a large deposited energy span, both ex-vivo and in-vivo.

Locoregional Treatments for Bridging and Downstaging HCC to Liver Transplantation.

Liver transplantation (LT) is the first-line treatment for patients diagnosed with unresectable early-stage hepatocellular carcinoma (HCC) in the setting of cirrhosis. It is well known that HCC patients within the Milan criteria (solitary tumour ≤ 5 cm or ≤3 tumours, each <3 cm) could undergo LT with excellent results. However, there is a growing tendency to enlarge inclusion criteria since the Milan criteria are nowadays considered too restrictive and may exclude patients who would benefit from LT. On the other hand, there is a persistent shortage of donor organs. In this scenario, there is consensus about the role of loco-regional therapy (LRT) during the waiting list to select patients who would benefit more from LT, reducing the risk of drop off from the waiting list as well as decreasing tumour dimension to meet acceptable criteria for LT. In this review, current evidence on the safety, efficacy and utility of LRTs as neoadjuvant therapies before LT are summarized.

Management of Liver Tumors during the COVID-19 Pandemic: The Added Value of Selective Internal Radiation Therapy (SIRT).

BACKGROUND: In the context of the coronavirus disease 2019 (COVID-19) pandemic, liver-directed therapies (LDTs) may offer minimally invasive integrative tools for tumor control. Among them, selective internal radiation therapy (SIRT) represents a safe, flexible and effective treatment. Purpose of this study is to present our experience with SIRT during the first wave of COVID-19 pandemic and provide an overview of the indications and challenges of SIRT in this scenario. METHODS: We retrospectively analyzed the number of patients evaluated by Multidisciplinary Liver Tumor Board (MLTB) and who were undergoing LDTs between March and July 2020 and compared it with 2019. For patients treated with SIRT, clinical data, treatment details and the best radiological response were collected. RESULTS: Compared to 2019, we observed a 27.5% reduction in the number of patients referred to MLTB and a 28.3% decrease in percutaneous ablations; transarterial chemoembolizations were stable, while SIRT increased by 64%. The majority of SIRT patients (75%) had primary tumors, mostly HCC. The best objective response and disease control rates were 56.7% and 72.2%, respectively. CONCLUSION: The first wave of the COVID-19 pandemic was characterized by an increased demand for SIRT, which represents a safe, flexible and effective treatment, whose manageability will further improve by simplifying the treatment workflow, developing user-friendly and reliable tools for personalized dosimetry and improving interdisciplinary communication.

Gastrointestinal Bleeding in Patients with SARS-CoV-2 Infection Managed by Interventional Radiology.

BACKGROUND: This study was conducted to evaluate the technical and clinical success of trans-arterial embolization (TAE) as a treatment of gastrointestinal bleeding (GIB) in Coronavirus Disease 2019 (COVID-19) patients and to describe its safety; moreover, we describe the characteristics of these patients. METHODS: Thirty-four COVID-19 hospitalized patients presented with GIB. Risk factors, drugs administered for COVID-19 infection, and clinical and biological parameters were evaluated. Furthermore, intraprocedural data and outcomes of embolization were analyzed. RESULTS: GIB was more frequent in male. Overweight, hypertension, diabetes, previous cardiac disease, and anticoagulation preadmission (48.5%) were frequently found in our population. Previous or actual COVID Acute respiratory distress syndrome (ARDS) and a high level of D-dimer were encountered in most cases. Upper GIB was more frequent than lower GIB. Technical and clinical success rates of embolization were 88.2% and 94.1%, respectively. The complication rate was 5.9%. CONCLUSIONS: Our study highlights the most frequent characteristics of COVID-19 patients with GIB. Embolization is feasible, effective, and safe.

Assessment of radiation sensitivity of unresectable intrahepatic cholangiocarcinoma in a series of patients submitted to radioembolization with yttrium-90 resin microspheres.

Radioembolization is a valuable therapeutic option in patients with unresectable intrahepatic cholangiocarcinoma. The essential implementation of the absorbed dose calculation methods should take into account also the specific tumor radiosensitivity, expressed by the α parameter. Purpose of this study was to retrospectively calculate it in a series of patients with unresectable intrahepatic cholangiocarcinoma submitted to radioembolization. Twenty-one therapeutic procedures in 15 patients were analysed. Tumor absorbed doses were calculated processing the post-therapeutic 90Y-PET/CT images and the pre-treatment contrast-enhanced CT scans. Tumor absorbed dose and pre- and post-treatment tumor volumes were used to calculate α and α3D parameters (dividing targeted liver in n voxels of the same volume with specific voxel absorbed dose). A tumor volume reduction was observed after treatment. The median of tumor average absorbed dose was 93 Gy (95% CI 81-119) and its correlation with the residual tumor mass was statistically significant. The median of α and α3D parameters was 0.005 Gy-1 (95% CI 0.004-0.008) and 0.007 Gy-1 (95% CI 0.005-0.015), respectively. Multivariate analysis showed tumor volume and tumor absorbed dose as significant predictors of the time to tumor progression. The knowledge of radiobiological parameters gives the possibility to decide the administered activity in order to improve the outcome of the treatment.

Microwave Ablation of Very-Early- and Early-Stage HCC: Efficacy Evaluation by Correlation with Histology after Liver Transplantation.

Microwave (MW) ablation is a worldwide-diffused technique for the percutaneous ablation of hepatocellular carcinoma (HCC). Nevertheless, the efficacy of this technique still needs to be confirmed in pathological specimens. The purpose of this study was to evaluate the efficacy of MW ablation by correlation with histology in excised liver samples at the time of liver transplantation (LT). All patients with MW-ablated HCC who subsequently underwent LT between 2012 and 2020 were retrospectively evaluated. In the explanted livers, the treated lesions were evaluated at pathology, and the necrosis was classified as complete or partial. Thirty-six HCCs were ablated in 30 patients (20.9 ± 6.1 mm, a range of 10-30 mm). Ablations were performed with a single insertion of a MW antenna under ultrasound or CT guidance. A complete radiological response was demonstrated in 30/36 nodules (83.3%) in 24/30 patients (80%) at imaging performed one-month after MW ablation. At pathology, of the 36 treated nodules, 28 (77.8%) showed a complete necrosis, and 8 (22.2%) showed a pathological partial necrosis. Good agreement was found between the imaging performed one-month after treatment and the complete pathological response (Cohen's k = 0.65). The imaging accuracy in detecting a complete response to treatment was 88.9%. All lesions with complete necrosis did not show recurrence at follow-up imaging until transplantation. The rad-path correlation in the explanted livers showed that MW ablation achieved a high rate of complete necrosis if a macroscopical complete ablation was obtained.

Duration of response after DEB-TACE compared to lipiodol-TACE in HCC-naïve patients: a propensity score matching analysis.

OBJECTIVES: To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable hepatocellular (HCC). METHODS: We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated. RESULTS: Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (n = 160) or DEB-TACE (n = 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (p = 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days; p = 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (p = 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6, p = 0.01). CONCLUSION: Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR. KEY POINTS: • Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization. • When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE. • In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.

Effect of Direct Endovascular Revascularization Based on the Angiosome Model on Risk of Major Amputations and Life Expectancy in Type 2 Diabetic Patients with Critical Limb Ischemia and Foot Ulceration.

BACKGROUND: We evaluated whether direct or indirect endovascular revascularization based on the angiosome model affects outcomes in type 2 diabetes and critical limb ischemia. METHODS: From 2010 to 2015, 603 patients with type 2 diabetes were admitted for critical limb ischemia and submitted to endovascular revascularization. Among these patients, 314 (52%) underwent direct and 123 (20%) indirect revascularization, depending on whether the flow to the artery directly feeding the site of ulceration, according to the angiosome model, was successfully acquired; 166 patients (28%) were judged unable to be revascularized. Outcomes were healing, major amputation, and mortality rates. RESULTS: An overall healing rate of 62.5% was observed: patients who did not receive percutaneous transluminal angioplasty presented a healing rate of 58.4% (P < .02 versus revascularized patients). A higher healing rate was observed in the direct versus the indirect group (82.4% versus 50.4%; P < .001). The major amputation rate was significantly higher in the indirect versus the direct group (9.2% versus 3.2%; P < .05). The overall mortality rate was 21.6%, and it was higher in the indirect versus the direct group (24% versus 14%; P < .05). CONCLUSIONS: These data show that direct revascularization of arteries supplying the diabetic foot ulcer site by means of the angiosome model is associated with a higher healing rate and lower risk of amputation and death compared with the indirect procedure. These results support use of the angiosome model in type 2 diabetes with critical limb ischemia.

Scar Pregnancy and Extrauterine Implants.

Cesarean scar pregnancy (CSP) is a rare occurrence consisting in the implantation of the embryo within the myometrium of a prior cesarean delivery scar. The CSP could be a dangerous condition for women because of the related complications such as placenta previa or accreta, uterine rupture, and hemorrhage. Therefore, early diagnosis and rapid treatment are crucial. Extrauterine implants or ectopic pregnancy (EP) consists in the implantation of an embryo in a site other than the endometrium of the uterine cavity. It occurs in 1%-2% of all reported pregnancies. The most common extrauterine location is the fallopian tube, which represents 96% of cases. The diagnosis of CSP and EP is based on history, clinical examination, levels of serum ß-human chorionic gonadotropin (ß-hCG), and ultrasonography findings. In last 20 years, new treatments were developed, varying from medical management, minimally invasive surgical approach and local treatment including systemic or local infusion of metotrexate (MTX), and uterine artery embolization (UAE). UAE has been used widely to control hemorrhage and preserve the uterus and it is considered an affective adjuvant treatment of CSP and EP, especially associated with other therapies.

Standardizing percutaneous Microwave Ablation in the treatment of Lung Tumors: a prospective multicenter trial (MALT study).

OBJECTIVES: To prospectively assess reproducibility, safety, and efficacy of microwave ablation (MWA) in the treatment of unresectable primary and secondary pulmonary tumors. METHODS: Patients with unresectable primary and metastatic lung tumors up to 4 cm were enrolled in a multicenter prospective clinical trial and underwent CT-guided MWA. Treatments were delivered using pre-defined MW power and duration settings, based on target tumor size and histology classifications. Patients were followed for up to 24 months. Treatment safety, efficacy, and reproducibility were assessed. Ablation volumes were measured at CT scan and compared with ablation volumes obtained on ex vivo bovine liver using equal treatment settings. RESULTS: From September 2015 to September 2017, 69 MWAs were performed in 54 patients, achieving technical success in all cases and treatment completion without deviations from the standardized protocol in 61 procedures (88.4%). Immediate post-MWA CT scans showed ablation dimensions smaller by about 25% than in the ex vivo model; however, a remarkable volumetric increase (40%) of the treated area was observed at 1 month post-ablation. No treatment-related deaths nor complications were recorded. Treatments of equal power and duration yielded fairly reproducible ablation dimensions at 48-h post-MWA scans. In comparison with the ex vivo liver model, in vivo ablation sizes were systematically smaller, by about 25%. Overall LPR was 24.7%, with an average TLP of 8.1 months. OS rates at 12 and 24 months were 98.0% and 71.3%, respectively. CONCLUSIONS: Percutaneous CT-guided MWA is a reproducible, safe, and effective treatment for malignant lung tumors up to 4 cm in size. KEY POINTS: • Percutaneous MWA treatment of primary and secondary lung tumors is a repeatable, safe, and effective therapeutic option. • It provides a fairly reproducible performance on both the long and short axis of the ablation zone. • When using pre-defined treatment duration and power settings according to tumor histology and size, LPR does not increase with increasing tumor size (up to 4 cm) for both primary and metastatic tumors.

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

The aim of the present study was to retrospectively analyze clinical outcomes of patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) treated with yttrium-90 radioembolization stratified by Milan PVTT score according to PVTT extension, tumor burden, and bilirubin levels. Seventy patients were included and classified into good (n = 15; 21.4%), intermediate (n = 33; 47.1%), and dismal (n = 22; 31.4%) prognostic groups. Median overall survival durations were 24.6 mo, 13 mo (hazard ratio = 3.2; 95% confidence interval [CI], 1.2-9.7; P = .016), and 5.9 mo (hazard ratio = 4.1; 95% CI, 1.4-13.4; P = .0096), respectively. The Milan score represents an easy tool to select patients with HCC with PVTT who may benefit from radioembolization.

Yttrium-90 Radioembolization in Unresectable Intrahepatic Cholangiocarcinoma: Results of a Multicenter Retrospective Study.

BACKGROUND: Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C). MATERIALS AND METHODS: The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8 years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared. RESULTS: Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5 months (95% CI: 11.1-16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (P < 0.05) independent factors, negatively associated with OS. CONCLUSION: Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.