Germ Cell Tumors Research Articles

Abdominopelvic imaging in the follow-up of testicular germ-cell tumors in adults: recommendations of the Scrotal and Penile Imaging Working Group of the European Society of Urogenital Radiology.

The Scrotal and Penile Imaging Working Group (SPIWG) of the European Society of Urogenital Radiology (ESUR) aimed to formulate recommendations on the imaging modalities and minimal technical requirements for abdominopelvic imaging in the follow-up of adult patients treated for testicular germ-cell tumors (TGCT). The SPIWG members performed an extensive literature search, reviewed the current clinical practice, and reached a consensus based on the opinions of experts in the field. Recurrence in patients treated for TGCT mainly occurs in retroperitoneal lymph nodes (LNs). Abdominopelvic CT and MRI are equivalent assessing retroperitoneal LNs. MRI has the advantage of avoiding radiation exposure, and moreover, diffusion-weighted images (DWI) may increase the detection rates without the need for contrast administration. In patients treated for stage I TGCT, the ESUR-SPIWG recommends MRI over CT for the detection of retroperitoneal LNs during the follow-up after treatment. CT, however, remains the follow-up imaging of choice in patients with advanced disease. When MRI is used, the recommended minimal requirements are at least one high-quality anatomical sequence (T1-WI or T2-WI) in axial and coronal planes, and DWI in the same axial plane, ≤ 4 mm contiguous slices from the diaphragm to the perineum. When CT is used, the recommended minimal requirement is a standard-dose contrast-enhanced CT in the portal-venous phase, scanned from the diaphragm to the perineum. In this paper, the ESUR-SPIWG provides recommendations on the imaging modalities and minimal technical requirements for abdominopelvic imaging in the follow-up of adult patients treated for TGCT. Question There are no recommendations on the preferred imaging modality or scan sequences required for abdominopelvic imaging in the follow-up after treatment for testicular cancers. Findings The European Society of Urogenital Radiology Scrotal and Penile Imaging Working Group (ESUR-SPIWG) provides recommendations for abdominopelvic imaging in follow-up after treatment for testicular cancers. Clinical relevance Recurrence of testicular germ-cell tumors mainly occurs in retroperitoneal lymph nodes. Both CT and MRI provide similar morphological assessments, but radiation exposure can be avoided by using MRI instead of CT.

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited. We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment. Predicted superpopulations included African (AFR, N=153), Admixed American (AMR, N=222), East Asian (EAS, N=67), European (EUR, N=968), and South Asian (SAS, N=42). Reported race and ethnicity and ancestry-based genetic superpopulations were non-randomly associated (p<0.001). Patients with an atypical teratoid rhabdoid tumor or meningioma were enriched for AFR ancestry (OR=2.6, FDR=0.01; OR=2.9, FDR=0.01, respectively). Among KIAA1549::BRAF fusion-positive low-grade glioma (LGG) diagnoses, EAS and SAS patients disproportionately harbored exon 15:09 breakpoints (FDR<0.05), and AMR patients demonstrated rare breakpoints, which were associated with lesser degree of surgical resection and worse event free survival (EFS) versus other breakpoints (HR=4.6, p=0.03). Non-EUR and AMR patients with germ cell tumors and SHH-activated medulloblastoma, respectively, exhibited worse EFS relative to EUR patients (HR=12.1, p<0.01; HR=5.2, p=0.03) and AFR patients with LGG (HR=16.4, p<0.01) or ependymoma (HR=5.5, p=0.02) had worse overall survival compared to EUR patients. We observed higher frequency of clinical trial enrollment among AMR patients across tumor histologies (OR=2.0, p=<0.01), but increased utilization of photon versus proton radiation relative to other superpopulations (OR=0.55, p=0.04). Genetic ancestry-associated differences exist across pediatric CNS tumor histological and molecular subtypes from PBTA and PNOC. Further investigation into genetic and socioeconomic factors contributing to these observed inequities is needed.

Altered retinal vasculature in childhood cancer survivors: Data from the German CVSS-study.

Childhood cancer is a risk factor for cardiovascular diseases in later life. Retinal examination allows to non-invasively observe the vasculature of an end-organ. We observe alterations in long-term childhood cancer survivors (CCS). In the Cardiac and Vascular Late Sequelae in Long-Term Survivors of Childhood Cancer-Study, 1002 CCS (23-48 years) having neoplasia prior to 15 years of age were prospectively enrolled in a general and ophthalmologic examination including fundus photography. Central retinal vessel equivalents (arterial: CRAE; venous CRVE) were measured and linear regression analysis was computed to compare CCS to controls from the population-based Gutenberg Health Study (GHS) with adjustment for potential cardiovascular and ophthalmological confounders. Differences in cancer types and treatments were explored. For 837 CCS (45.3% female), CRAE and CRVE were conducted. Both were smaller in CCS previously having leukaemia, central nervous system tumour, neuroblastoma, renal tumour, malignant bone tumour, soft tissue sarcoma and germ cell tumour than in GHS controls. No difference was found for CCS with prior lymphoma. Previous radiotherapy of head or neck was associated with a smaller CRVE. Higher mean arterial blood pressure and intake of antihypertensive medication were associated with smaller CRAE. Retinal vasculature is altered in CCS leading to smaller retinal arteries and veins. Our finding indicates that childhood cancer and its treatment leads to systemic alterations of the microcirculation on both branches of the vasculature system. While the retinal venous vasculature is altered by radiotherapy, the lower vessel width of the arterial branch is associated with arterial hypertension.

Important changes to the 2022 WHO classification of testicular tumours : Aguide for diagnostics

The 5thEdition of the "WHO Classification of Tumours: Urinary and Male Genital Tumours" introduces several significant updates to the classification of testicular tumours. These updates include revised terminology for special germ cell tumour subtypes (neuroectodermal and neuroendocrine tumours) of the testis. Additionally, the signet-ring stromal tumour and myoid gonadal stromal tumour have been introduced as distinct entities within the sex-cord stromal tumours. Moreover, new combined sections have been created for lymphatic neoplasms and soft tissue tumours of the urinary and male genital tract.

Sacral tumors: a comprehensive review of imaging, diagnostic challenges, and tumor mimics.

The sacrum can harbor a diverse group of both benign and malignant tumors, including metastases. Primary tumors of the sacrum can arise from bone, cartilage, marrow, notochordal remnants, or surrounding nerves and vessels. Among a variety of primary tumors of the spine,chordoma, germ cell tumors and Ewing's sarcoma are recognized for their propensity to occur in the sacrum. Imaging is essential in diagnosis, pretreatment evaluation, and assessment of response to treatment.Radiography,CT and MRI are the primary modalities in assessingmorphology andtumor extent whereas PET/CT is crucial in the evaluation of systemic disease in the setting of myeloma, lymphoproliferative disease, and metastasis. A definitive diagnosis is not always achievable by imaging as some tumors lack specific imaging features. However, as we detailin thiscomprehensivereview, many entities have characteristic clinical and epidemiological factors as well as typical imaging findings that can help make either a confident diagnosis or offer a narrow list of differentials. We discuss a wide range of benign and malignant, primary, and secondary tumors that can involve the sacrum, highlighting the pertinent clinical details and typical imaging findings of these entities, enabling the reader to develop and apply a systematic approach to evaluating sacral masses on imaging. We also briefly describe non-neoplastic tumor mimics, which include developmental entities, infections, and insufficiency fractures.

Networks of pre-diagnostic circulating RNA in testicular germ cell tumour

Testicular germ cell tumour (TGCT) is a malignancy with known inherited risk factors, affecting young men. We have previously identified several hundred differentially abundant circulating RNAs in pre-diagnostic serum from TGCT cases compared to healthy controls. In this study, we performed Weighted Gene Co-expression Network Analysis (WGCNA) on mRNA and miRNA data from these samples. Central genes (hub genes) enriched functional pathways, and regulatory feature prediction were identified for all TGCT subtypes together and according to histology. The TGCT susceptibility genes TEX14, NARS2, and G3BP2, were identified as hub genes in both seminoma and non-seminoma networks. We also identified UBCA1, RCC1, FMR1, OAS3, and UBE2W as hub genes associated with TGCT. The genes OAS3 and UBE2W have previously been associated with testicular dysgenesis. Furthermore, network module analysis indicated transcription factors for oestrogen-related receptors to have a potential role during development of TGCT. The overlap between mRNA network hub genes and TGCT susceptibility genes indicates a common role in TGCT development.

Familial History in Ovarian Teratomas Is a Frequent Event: 22 Years' Experience at a Single Center.

Ovarian mature teratoma represents the most common benign neoplasm among pediatric germ cell tumors. This study reports the prevalence and characteristics of familial forms identified in a single center over 22 years in order to better understand possible familial predispositions to ovarian teratoma. The records of all patients who were surgically treated for ovarian teratoma between 2000 and 2022 were retrospectively reviewed. Families were systematically asked about a possible family history of ovarian tumors (benign or malignant) or testicular germ cell tumors. Among the 136 patients operated on for ovarian teratoma, 24 cases of familial form (18%) were identified. Patients with familial history of ovarian mature teratoma were more likely to have multifocal tumors at diagnosis and metachronous lesions over time (p = 0.032 and p = 0.018, respectively) compared with patients without familial history. The family history concerned first-degree relatives in 12/24 cases (50%) including one case of twin monozygotic sisters, and affected two consecutive generations in three cases. A systematic examination made it possible to find up to 18% of familial forms in mature teratomas of the ovary, which in these cases seem to be more likely multifocal. The underlying genetic mechanisms are likely to be heterogeneous. Further work seems to be necessary to provide a better understanding of the genesis of germ cell tumors.

Germ cell tumors in children.

Pediatric germ cell tumors represent a rare but biologically diverse group of neoplasms arising from pluripotent primordial germ cells. The 2022 edition of the WHO Classification of Pediatric Tumors introduced the first organ independent classification of germ cell tumors, reflecting advances in molecular biology, histopathology, and clinical practice. This review highlights the key changes, including the refined distinctions between the different subtypes. These updates enhance diagnostic accuracy and provide a framework for understanding age-dependent differences in tumor biology and behavior. Emphasis is placed on integrating the new classification into multidisciplinary care, particularly in addressing diagnostic challenges in pre- and post-pubertal-type germ cell tumors. By bridging the gap between histopathology and oncology, the updated classification represents a pivotal step forward in improving outcomes for children with germ cell tumors.

The effects of regular exercise on cognitive and cardiometabolic health in testicular cancer survivors subjected to platinum-based chemotherapy.

Platinum-based chemotherapy provides curative treatment to more than 95% of patients with testicular germ cell tumor but it has negative cardiometabolic and neurological effects. Regular exercise can alleviate late chemotherapy-related toxicities. We examined the impact of a 6-month supervised aerobic-strength training on cognitive and cardiometabolic health and residual level of platinum in cancer survivors. Twenty-eight middle-aged (42.1±7.6 years) testicular germ cell tumor survivors subjected to platinum-based chemotherapy (1-8 cycles, 0-24 years ago) were recruited into exercise (n=20) and control (n=8) groups. Effects of 6-month exercise training on the whole-body and muscle metabolism, cognitive functions, cardiopulmonary fitness, residual plasma platinum, and plasma adiponectin were examined. Exercise intervention improved cardiopulmonary fitness and cognitive functions, reduced residual plasma platinum, visceral adiposity and muscle lipids, improved glucose (glycosylated hemoglobin) and lipid (high-density lipoprotein cholesterol) metabolism, and enhanced dynamics of muscle post-exercise phosphocreatine recovery. Exercise-related decline in plasma platinum was paralleled by decline of muscle glycerophosphocholines and by the enhanced metabolic flexibility during low-intensity exercise, and predicted training-induced increase in cognitive functions. The 6-month exercise intervention resulted in improved cognitive and cardiometabolic health in testicular germ cell tumor survivors, which was paralleled by reduced plasma platinum, providing evidence that structured supervised exercise brings multiple health benefits to testicular germ cell tumor survivors.

Comparison of serum and plasma microRNA expression levels in patients with germ cell tumours.

Comparison of serum and plasma microRNA expression levels in patients with germ cell tumours.

Extracranial and nonvaginal extragonadal malignant germ cell tumors: 12 cases at a Chinese institution over the last 38years.

To provide a comprehensive understanding and propose a strategy for the management of extragonadal malignant germ cell tumors (EMGCTs) arising from extracranial and nonvaginal sites. We retrospectively reviewed the cases of 12 patients with EMGCTs arising from extracranial and nonvaginal sites treated in our center over the past 38years. Data on clinicopathological characteristics, treatment modalities, and follow-up information were analyzed. Among 209 patients diagnosed with EMGCTs, 12 women (5.7%) with EMGCTs of extracranial and nonvaginal sites were identified. These patients had tumors in the sacrococcygeal region (n = 4), abdominal cavity (n = 3), groin region (n = 2), uterus (n = 2), and mediastinum (n = 1). The median age at diagnosis was 23years. Symptoms included abnormal uterine bleeding (n = 3), abdominal discomfort (n = 3), compression symptoms (n = 3), palpable mass (n = 2), and asymptomatic (n = 1). Yolk sac tumors (YSTs) were the most common histologic type. The median level of serum alpha-fetoprotein (AFP), a sensitive tumor marker, was 8216ng/ml (2.7-74,157ng/ml). One patient started bleomycin/etoposide/cisplatin without a pathologic diagnosis based on clinical diagnosis (high AFP levels and imaging findings), and 11 patients started chemotherapy following tumor biopsy or surgical resection. During the follow-up, one patient suffered a recurrence, two patients were alive with disease, and nine patients were disease-free. Extracranial and nonvaginal EMGCTs are a heterogeneous group of tumors due to their varied onset ages, location, and clinical presentation. An all-around clinical evaluation is crucial for selecting appropriate treatment. Most patients achieve agood prognosis after surgical resection and chemotherapy. Patients with these rare diseases may benefit from individualized treatment and timely referral to experienced medical centers.

Pre-orchiectomy semen analysis in patients with testicular germ cell tumours and comparison with healthy men and with patients with other malignancies

Purpose Subfertility is a well-known aftermath of treatment of testicular germ cell tumours (GCTs). Growing evidence suggests reduced semen quality also before therapy. The present study aimed to evaluate pre-orchiectomy semen parameters in GCT patients and to compare the results with controls. Methods GCT patients providing semen for cryopreservation before orchiectomy during 2012 - 2023 were retrospectively enrolled (TT cohort). Controls consisted of healthy volunteers for sperm donation (HD), and of patients with other malignancies (OM). The following parameters were recorded in each participant: ejaculate volume (EV; ml), total sperm count in ejaculate (TSC), and proportion of progressive motility (PM) (%). Descriptive statistical methods were used to compare the 3 populations with each other. Results A total of 664 subjects were included, thereof 163 TT, 289 HD, and 212 OM. Median ejaculate volume was 3.0 ml, 3.5 ml, and 3.4 ml; median TSC was 56.9 x106, 207 x106, and 152 x106; median PM was 40%, 40.2%, and 43% in TT, HD, and OM, respectively. TSC, EV and several secondary parameters of semen quality observed in TT were significantly worse than those in the two control cohorts. HD and OM were within normal limits with regard to TSC and PM and were different in only a few secondary parameters. Conclusion This study confirmed significantly lower pre-orchiectomy semen quality in GCT patients in comparison to healthy males and to patients with other malignancies. Subfertility is an intrinsic feature of GCT preceding treatment that needs to be considered by care-givers.

Depletion of TP53 in Human Pluripotent Stem Cells Triggers Malignant-Like Behavior.

Human pluripotent stem cells (hPSCs) tend to acquire genetic aberrations upon culture in vitro. Common aberrations are mutations in the tumor suppressor TP53, suspected to confer a growth-advantage to the mutant cells. However, their full impact in the development of malignant features and safety of hPSCs for downstream applications is yet to be elucidated. Here, TP53 is knocked out in hPSCs using CRISPR-Cas9 and compared them with isogenic wild-type hPSCs and human germ cell tumor lines as models of malignancy. While no major changes in proliferation, pluripotency, and transcriptomic profiles are found, mutant lines display aberrations in some of the main chromosomal hotspots for genetic abnormalities in hPSCs. Additionally, enhanced clonogenic and anchorage-free growth, alongside resistance to chemotherapeutic compounds is observed. The results indicate that common TP53-depleting mutations in hPSCs, although potentially overlooked by standard analyses, can impact their behavior and safety in a clinical setting.

Repeated ionizing radiation exposure induces TRIP13 expression, conferring radioresistance in lung cancer cells

Repeated ionizing radiation exposure induces TRIP13 expression, conferring radioresistance in lung cancer cells

Germ Cell Neoplasia In situ in Undescended Testis: A Myth or Reality?

ABSTRACT Background: Untreated cryptorchid testes are in risk of intratubular germ cell neoplasia and subsequently may give rise to invasive germ cell tumors. Materials and Methods: Tissue samples were obtained from patients undergoing orchidectomy or orchiopexy and were subjected to routine histopathological and immunohistochemical examinations. Results: Forty-three patients were enrolled in this study out of which 30 samples were collected. The mean age of patients was 9.16 years. One case (6.7%) showed positivity of the germ cell neoplasia with anto placental alkaline phosphatase and Anto CD-117 positive. Other histopathological findings such as fibrocollagenous tissue and Leydig cell hyperplasia were reported. Conclusion: Early surgical management is of importance for a better outcome in cases of undescended testes.

Optimal treatment strategy for central nervous system non-germinomatous germ cell tumors: A systematic review and meta-analysis.

To determine the optimal treatment modality for central nervous system (CNS) non-germinomatous germ cell tumors (NGGCTs). A search of Medline, Embase, Web of Science and Cochrane Library was conducted up to September 30, 2024. All studies were considered, covering all CNS NGGCT patients with an informative treatment approach. Pooled risk ratio (RR) and 95 % confidence interval (CI) were calculated. Total 42 studies were included in the systematic review. Pooled risk ratio (RR) indicated a 28 % lower failure rate for the gross total resection (GTR) compared to the non-GTR group [RR = 0.72, 95 % CI (0.55, 0.95), P = 0.02]. Meta-analysis showed that craniospinal irradiation (CSI) was associated with a significantly lower failure rate for localized NGGCTs [RR = 0.53, 95 % CI (0.38, 0.74), P = 0.0002]. Meta-analysis manifested that the risk of any failure event was 27 % lower in the chemoradiotherapy group compared to radiotherapy alone [RR = 0.73, 95 % CI (0.55, 0.98), P = 0.04]. Total 21 studies reported treatment-related acute and/or late toxicity, combination chemotherapy increased acute toxic, and expanded RT field and/or dose mainly increased late toxicity. GTR was associated with better outcomes in terms of any failure event, and CSI was particularly beneficial for localized NGGCTs patients in reducing any failure event rate, and combination chemotherapy further reduced the failure risk. If CSI is combined with chemotherapy, the total RT dose can be appropriately reduced.

Resection of large mediastinal germ cell tumor in an adolescent

Resection of large mediastinal germ cell tumor in an adolescent

External pressure induced the dysfunction of Sertoli cells via the Fas/FasL signaling pathway

Cryptorchidism, a condition where the testis fails to fully descend into the scrotum during development, is associated with elevated environmental temperatures and pressures, leading to male infertility and germ cell tumors. Factors such as oxidative stress and high temperatures contribute to infertility in cryptorchidism. This study aims to explore how external pressure affects Sertoli cells and discover new mechanisms affecting spermatogenesis in cryptorchidism. Sertoli cells were subjected to various pressure levels (0 mmHg, 25 mmHg, 50 mmHg, 100 mmHg) and durations (0 h, 2 h, 4 h) using an enzyme-linked immunosorbent assay (ELISA) to measure androgen binding protein (ABP) and inhibin B (INH B) secretion. Cell morphology changes were observed using immunofluorescence; apoptosis rates were measured with terminal-deoxynucleotidyl transferase mediated nick end labelling (TUNEL) assay and flow cytometry; ultrastructural variations were examined via transmission electron microscopy; and the expression of apoptosis-related proteins (Fas, FasL, caspase 3, and caspase 8) was analyzed through immunohistochemistry, real-time polymerase chain reaction (real-time PCR), and western blotting. The results showed that elevated pressure suppressed ABP and INH B secretion from Sertoli cells. Structural changes were observed under pressure, including cytoskeleton loosening and nuclear fragmentation. Apoptosis rates increased with higher pressure levels. Ultrastructural analysis revealed chromatin changes, apoptotic bodies, and mitochondrial alterations. Increased expressions of Fas and FasL were detected, along with elevated levels of caspase 3 and caspase 8. The caspase 8 inhibitor blocked pressure-induced apoptosis and caspase 3 activation, while the cytochrome C inhibitor did not show the same effect. Our findings suggested that external pressure induces apoptosis of Sertoli cells via the Fas/FasL signaling pathway, potentially contributing to male infertility associated with cryptorchidism.

Study of the genomics and transcriptomics profiles of male-infertility genes in human prostate cancer: an in silico analysis

The World Health Organization has considered the infertility as an international public health problem. Infertility affect nearly 1 in 7 couples and male component contributes to 50% of infertility cases. There is a clear link between male infertility and some cancers such as testicular germ cell, prostate and colon cancers. Two possibilities support this finding: 1) Cancer treatments can affect the fertility factors 2) Genetic profile of infertility genes have been altered in cancer patients. Although the previously published researches have mostly focused on the first factor, no article has yet confirmed the role of genetic factors. In this in silico study, we collected the large number of genes (n = 17703) involved in infertility. These genes were collected from NGS panel tests of male infertility and comprehensive literature review or online data base. The Prostate Adenocarcinoma genomic and transcriptomics raw data were downloaded from the cBioPortal Cancer dataset. This included with 494 patients of Prostate Cancer with 494 mutation data, 489 with CNA and 493 with RNA seqV2 data. TCGA RNA-Seq raw data was extracted in R using the cgdsr extension package with a threshold of ±2 relative to normal samples. The observed data showed that male infertility genes have been distributed through the human genome. Among the 17703 analyzed genes of this study, the genomic profile of three genes including OR9Q1, H4C6 and PSG7 were changed approximately in 100% of (n = 493) patients. In most of patients (>98%), genetic alteration was related to change in gene expression. In conclusion, this study showed that the genomic and transcriptomics patterns of some male-infertility genes are notably altered in patients of prostate cancer and suggested a possible role of genetic factors in occurrence of infertility in cancer patients. Our information can be used as a source for the design of genetic database of male-infertility.

Efficacy and Safety of Three Cycles of TIP and Sequential High Dose Chemotherapy in Patients with Testicular Non-Seminomatous Germ Cell Tumors

Background: Salvage treatment options have not been validated in relapsed or refractory germ cell tumors. Moreover, the study populations including these patients have different heterogeneities. This study aimed to evaluate the efficacy and safety of three cycles of TIP sequential high-dose chemotherapy in patients with testicular non-seminomatous germ cell tumors who relapsed or had a refractory course after first-line platinum-based chemotherapy. Methods: Data of 141 patients who underwent three cycles of TIP followed by HDCT due to relapsed/refractory gonadal NSGCTs after first-line cisplatin-based chemotherapy (BEP/EP) at Gulhane School of Medicine Hospital Medical Oncology Department between January 2017 and May 2024 were evaluated retrospectively. Patients underwent a treatment regimen consisting of two phases. Initially, they received three cycles of induction therapy using a combination known as TIP, which includes paclitaxel, ifosfomide, and cisplatin. Following this, they were given a single cycle of high-dose chemotherapy. Demographic and clinicopathological features of patients and treatment-related complications and survival outcomes were recorded. Results: Median follow-up for all patients was 35.2 (95% CI, 29.45 to 41.07) months. Complete Response (CR) or marker negative Partial Response (PR) after HDCT was achieved in 84 (59.6%) patients. Median time for PFS not reached (NR) (95% CI, NR) in the entire group. The 2-year PFS rate was 51.8%. Median time for OS not reached (95% CI, NR) and the 2-year OS rate was 72.3%. The most common myelotoxicity observed after HDCT until engraftment was grade 4 neutropenia (100%) and grade 4 thrombocytopenia (96.5%). Transplantation-related mortality occurred in 7.1% of patients. Variables that remained statistically significant in multivariable analysis and were associated with poor prognosis for overall survival were platinum refractory disease and AFP and/or beta HCG elevation. Conclusions: Significant survival can be achieved after three cycles of TIP consecutive HDCT, while treatment-related mortality was found to be low.