SURVIVAL IMPACT OF SKELETAL METASTASIS ON BONE SCINTIGRAPHY IN PATIENTS WITH GERM CELL TUMOURS

Objective: Our aim was to determine the frequency of skeletal metastasis in germ cell tumours (GCT) at baseline and relapse on conventional technetium-99m methylene diphosphonate (Tc-99m MDP) whole body bone scan (bone scan) and to evaluate the effect of bone metastases on survival. Materials and Methods: Electronic medical records of histologically proven GCT over 64 months were retrospectively analysed. Basic demographic and histologic information were correlated with the presence of osseous and visceral metastases. 5-year disease-free survival (DFS) and overall survival (OS) were calculated in presence, the absence of bone metastases at baseline and at relapse. Results: A total of 130 gonadal and extragonadal GCT patients underwent Tc-99m MDP bone scans; four with insuf cient data were excluded from the study. 47% were females and 53% were males with the age range of 1 month – 72 years. 105 (83%) were under 18 years of age. Osseous metastasis was detected in 12 (9.5%). Two (17%) had solitary and 10 (83%) had multifocal skeletal metastases. Clinically, 83% had localised bone pain. Osseous metastases were more frequently associated with mixed GCT and yolk sac tumour. 50% of mediastinal GCT developed bone metastases. 42% died within 4–18 months. There was a statistically signi cant impact of visceral metastases on DFS and OS. OS at 5 years in patients without bone metastases, with bone metastases at baseline and bone metastases at relapse, was 77%, 38% and 75%, respectively. 5-year DFS for the same cohort groups was 63%, 38% and 20%, respectively. Conclusion: Osseous involvement was found in 9.5% of GCT patients undergoing diagnostic Tc-99m MDP bone scan. Baseline skeletal evaluation for metastases should be done, particularly in the case of bone pains or known systemic metastases. Although skeletal relapses are rare, they have a grim outcome. Key words: Bone scintigraphy, germ cell tumours, skeletal metastases

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Kezdeti tapasztalatok a 99mTc-PSMA-SPECT/CT-vel prosztatarákos betegekben

Orvosi Hetilap ◽

10.1556/650.2018.31128 ◽

2018 ◽

Vol 159 (35) ◽

pp. 1433-1440

Author(s):

István Farkas ◽

Zsuzsanna Besenyi ◽

Anikó Maráz ◽

Zoltán Bajory ◽

András Palkó ◽

...

Keyword(s):

Prostate Cancer ◽

Bone Metastases ◽

Bone Scintigraphy ◽

Transmembrane Protein ◽

Tracer Uptake ◽

Whole Body ◽

Primary Prostate Cancer ◽

Cancer Tumor ◽

Visceral Metastases ◽

Male Patients

Abstract: Introduction: The prostate-specific membrane antigen (PSMA) is a transmembrane protein, that is highly expressed on the surface of prostate cancer cells. In the last few years, several PSMA-specific ligands have been developed, that can be successfully used to detect primary prostate cancer, tumor recurrences and metastases as well. Aim: The goal of our work was to examine the clinical application of a 99mtechnetium-labeled PSMA-radiopharmaceutical as part of the routine diagnostics of prostate cancer. Method: We examined 15 male patients with verified prostate adenocarcinoma with suspicion of progression or recurrence of the disease. We performed whole-body PSMA-SPECT/CTs and multiparametric MRIs of the prostate and the pelvic regions within a week. We used 99mTc-mas3-y-nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were visually evaluated by independent observers. The results were compared with the follow-up bone scintigraphies as well. Results: Twenty-two PSMA-positive lesions were found. Nine of them were localized outside, 13 were within the MRI’s field of view. From these 13 lesions, 7 matched with the SPECT/CT results and in 5 cases the MRI images showed no abnormalities. In one case, bone metastasis was suspected on the MRI scan but there was no corresponding pathological tracer uptake on the SPECT images. In two patients, none of the examinations showed signs of prostate malignancy. Four patients had PSMA-positive bone metastases. One of them had a matching PSMA/SPECT and bone scintigraphy result and in one case the PSMA examination showed metastasis in contrast to the negative bone scintigraphy. Conclusion: PSMA-SPECT/CT with 99mTc-mas3-y-nal-k(Sub-KuE) is a promising diagnostic tool. This technique is capable of visualizing bone metastases and it can detect local recurrences and visceral metastases as well. Orv Hetil. 2018; 159(35): 1433–1440.

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Pattern of Skeletal Metastasis in Breast Cancer Patients Attending INMAS, Rajshahi

Bangladesh Journal of Nuclear Medicine ◽

10.3329/bjnm.v21i1.40248 ◽

2019 ◽

Vol 21 (1) ◽

pp. 21-25

Author(s):

Munshi Md Arif Hosen ◽

Nasrin Begum ◽

Pervez Ahmed ◽

Mosharrof Hossain ◽

Shefaly Khatun ◽

...

Keyword(s):

Breast Cancer ◽

Cervical Spine ◽

Lumbar Spine ◽

Bone Metastases ◽

Cancer Patients ◽

Bone Scan ◽

Skeletal Metastasis ◽

Skeletal Metastases ◽

Breast Cancer Patients ◽

Common Site

Breast cancer is the most common malignant tumor of females, the incidence increases with age. Bone is the most common site to which breast cancer metastasizes. Between 30% to 85% of patients with metastatic breast cancer develop bone metastases during the course of the disease. Bone scan is the most commonly used means of detecting bone metastasis; it visualizes increases in osteoblastic activity and skeletal vascularity. Many radio-pharmaceuticals (radionuclides) have been used in bone scan including technetium-99m bound to methylene diphosphonate (MDP). Published sensitivity and specificity rates of bone scan for diagnosis varies, with sensitivity ranging from 62% to 100% and specificity from 78% to 100%. However, bone scan is generally considered sensitive for detecting bone metastases on whole-body images.The aim of this study was to evaluate the pattern of distribution of skeletal metastases in patients with breast carcinoma by using Tc-99m MDP bone scan. A retrospective study was conducted on 245 consecutive female breast carcinoma patients irrespective of clinical staging, menopausal status and pre-operative / post- mastectomy status, referred for bone scan to Institute of Nuclear Medicine and Allied Sciences, Rajshahi from July 2015 to June 2017. The mean age of the patients was 43.4 ± 13.8 years (mean ± SD) with range from 29 to 66 years. Bone scan was performed by an intravenous bolus injection of 20 mCi Tc99m-MDP. Bone phase images were taken at three hours after injection of the radiotracer. Out of 245 studied patients, 163 patients (66.53%) were negative for skeletal metastasis and 82 patients (33.47%) were positive for skeletal metastasis. Out of 82 patients with positive skeletal metastasis, 68 (82.93%) patients had multiple sites (two or more) and 14 (17.07%) patients had solitary site of bony involvement. Out of 68 patients with multiple sites of skeletal metastasis, highest number was noted in thoraco-lumbar spine (80.89%), followed by ribs including sternum and clavicle (57.35%), pelvic bones (47.06%), upper extremities including scapula (41.18%), lower extremities (33.82%), cervical spine (23.53%) and skull bone (8.82%). Among 14 patients with solitary skeletal metastasis, maximum number was noted in thoraco-lumbar spine (64.29%), followed by cervical spine (14.29%), pelvic bone (07.14%), ribs (07.14%) and sternum (07.14%). Skeletal metastases were much more common in multiple sites than solitary lesion in breast cancer patients. Thoraco-lumbar spine was the most common site of involvement in both solitary and multiple lesions in our study. Axial skeleton was more commonly involved than the appendicular skeleton. Bone scan may pick up bone metastases up to 18 months earlier than conventional radiology, with an average lead of four months. 99m Tc- MDP bone scan is very cost effective in comparison to other imaging modalities (CT, MRI, and PET) and play a major role in early detection of skeletal metastasis in breast cancer patients. Bangladesh J. Nuclear Med. 21(1): 21-25, January 2018

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Bone scan index on bone scintigraphy and radiation therapy for bone metastases from cancers other than prostate and breast cancers: a retrospective observational study

10.21203/rs.3.rs-21723/v1 ◽

2020 ◽

Author(s):

Naoya Ishibashi ◽

Toshiya Maebayashi ◽

Yuki Kimura ◽

Masahiro Okada

Keyword(s):

Prostate Cancer ◽

Overall Survival ◽

Radiation Therapy ◽

Bone Metastases ◽

Bone Scintigraphy ◽

Bone Scan ◽

Whole Body ◽

Study Cohort ◽

Breast Cancers ◽

Bone Scan Index

Abstract Background A low bone scan index that is associated with a better prognosis in patients with bone metastases from prostate or breast cancer, the former often being osteolytic, has been established. In this study we aimed to use new automatic analysis software (VSBONE BSI; Nihon Medi-Physics, Tokyo, Japan) to investigate whether the pre-radiation therapy bone scan index, derived from bone scintigraphy images, is a prognostic indicator in patients undergoing radiation therapy for bone metastases from cancers other than breast or prostate cancer. Methods In this retrospective single institution study, we analyzed data of 51 patients who had undergone whole-body scintigraphy before receiving radiation therapy for bone metastases from cancers other than breast and prostate cancer between 2013 and 2019. Their bone metastases were classified as osteoblastic, osteolytic, or mixed and their pre-radiation bone scan indexes were automatically calculated using newly developed software (VSBONE BSI; Nihon Medi-Physics, Tokyo, Japan). Univariate and multivariate analyses were performed to identify associations between selected clinical variables and overall survival. Results We did not find a significant association between BSI and overall survival, possibly because osteolytic lesions may be underestimated by bone scan indexes. However, we did find that younger patients (aged less than the median of 66 years at the time of bone scintigraphy or of diagnosis of bone metastases) had significantly better overall survivals than older patients (P = 0.016 and P = 0.036, respectively). Additionally, bone scan indexes were significantly lower in patient with solitary or osteolytic bone metastases than in those with osteoblastic or mixed bone metastases (P = 0.035 and P = <0.001, respectively), and significantly higher in those with lung cancer than in those with other types of cancer (mean BSI 3.26% vs. 1.97%; P = 0.009). Conclusions The only significant association with survival identified in this study was for age at the time of bone scintigraphy and at time of diagnosis of bone metastases. In particular, we found no association between bone scan index and survival in the whole study cohort.

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Role of Whole-Body Tc 99m MDP Bone Scintigraphy for Evaluating Skeletal Metastasis in Patients with Lung Cancer

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v42i3.32214 ◽

2017 ◽

Vol 42 (3) ◽

pp. 132-136

Author(s):

Rawnak Afrin ◽

Fatema Sultana Haque ◽

Shankar Kumar Biswas ◽

Sanowar Hossain ◽

Mahmood Uz Jahan

Keyword(s):

Lung Cancer ◽

Cell Carcinoma ◽

Bone Scintigraphy ◽

Bone Scan ◽

Metastatic Cancer ◽

Lumbar Vertebrae ◽

Cost Effective ◽

Skeletal Metastasis ◽

Whole Body ◽

Thoracic Vertebrae

Lung cancer is the third most common site of origin of metastatic cancer deposits in bone, after breast and prostate. Its metastasis to bone is one of the most aggressive tumors and has a very unfavorable prognosis. This retrospective descriptive study was designed to detect the skeletal metastasis of carcinoma (Ca) lung patient by Tc 99m MDP bone scan. The medical records of all patients attended between January 2015 and July 2015 with a diagnosis of lung cancer were reviewed. Lung cancer in all patients was confirmed pathologically, and patients underwent whole-body bone scan for evaluating skeletal metastasis. Patient with clinical and laboratory evidence of infection, trauma, metabolic disease or arthropathy were not included in the study. Bone scan was done after three hours of intravenous administration of 20mci Tc 99m MDP (methylene diphosphonate) and images were obtained on a gamma camera. The mean age of the patients was Mean ± SD was 55.5 ± 12.5 with range from 31 to 90 years. Out of 47 cases, 36 (76.59%) were diagnosed as positive for skeletal metastasis by bone scan and 11 (23.41%) were negative for bony metastasis. Among 36 positive patients, 28 patients (77.86%) were histopathologically diagnosed as adenocarcinoma, 7 patients (19.44%) had squamous cell carcinoma and only one patient (2,7%) had small cell carcinoma. Bone scan findings were compared by either conventional X-ray/CT scan/MRI /pathologically. In present study, the distribution of lesions in bone scan had recorded. Maximum 47.22 % lesions were found in ribs, 27.77% lesions were in lumbar vertebrae, 19.44% in thoracic vertebrae, 19.44% in joints, 16.66% in long bones (femur and humerus), 11.11% in skull bones, 22.22% in pelvic bones, 5.55% in clavicle and 2.77% in scapula. Tc 99m MDP bone scan plays a pivotal role for detection of skeletal metastasis which is very essential to manage Ca lung patient. As bone scintigraphy is very cost effective in govt. nuclear medicine centre in comparison to other imaging modalities, so it can play a major role in detecting skeletal metastasis in ca lung patients in a developing country like Bangladesh.

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Potential Application of Bone Scintigraphy in Nasopharyngeal Carcinoma With Skull Base and Adjacent Bony Involvement

Journal of Global Oncology ◽

10.1200/jgo.18.81600 ◽

2018 ◽

Vol 4 (Supplement 2) ◽

pp. 202s-202s

Author(s):

A.Z. Zanial ◽

S.Z. Amir Hassan

Keyword(s):

Nasopharyngeal Carcinoma ◽

Skull Base ◽

Bone Scintigraphy ◽

Skeletal Metastasis ◽

Whole Body ◽

Skeletal Metastases ◽

Whole Body Imaging ◽

Body Imaging ◽

Skull Base Lesions ◽

Bony Involvement

Background: Bone scintigraphy has an established role to evaluate skeletal metastasis by detecting lesions earlier compared with radiographic changes. Skull base and adjacent bony involvement could possibly be evaluated using bone scintigraphy and might influence nasopharyngeal carcinoma (NPC) treatment planning. Skull base lesions in NPC are also associated with concomitant skeletal metastases. Aim: To determine clinical characteristics of NPC patients with skull base lesions and adjacent bony involvement who underwent bone scintigraphy and their scan findings. Methods: Bone scintigraphy performed for 87 NPC patients between June 2014 and February 2018. Whole-body imaging acquired at 3 hours after 99mTc methylene diphosphonate (MDP) injection. Clinical information and scintigraphic findings were compiled. Patients with prior evidence and/or bone scintigraphic features of skull base lesions or adjacent bony involvement were included (n = 46). Synchronous malignancy or ongoing bone infection cases were excluded. Results: 17 patients had prior evidence of skull base or adjacent bony involvement that were all subsequently positive on bone scintigraphy. We detected another 29 patients with MDP-avid skull base or adjacent bony involvement. Average age of entire cohort was 51 years. Approximately 78% were males. Majority were ethnic Chinese (48%). Most patients (57%) had stage 4 diseases prior to bone scintigraphy with 9 patients demonstrating distant metastasis mainly to lungs and bones. Only 28 patients were receiving ongoing treatment. Overall, 18 patients (39%) showed concomitant MDP-avid skeletal metastases on whole-body imaging. Patients whom already had existing documented distant metastasis were significantly associated with concomitant MDP-avid skeletal metastases ( P < 0.05), while other parameters including gender, age, ethnicity, disease staging and treatment status showed no significant correlation. Conclusion: Bone scintigraphy could potentially be used to assess skull base and adjacent bony involvement besides concomitant skeletal metastasis among our cohort of NPC patients.

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Scintigraphy with 99m Tc-Phosphonate and 67Gallium in Patients Suspected of Primary Bone Tumors

Nuklearmedizin ◽

10.1055/s-0037-1620567 ◽

1982 ◽

Vol 21 (04) ◽

pp. 136-139 ◽

Cited By ~ 2

Author(s):

C.-J. Edeling

Keyword(s):

Soft Tissue ◽

Bone Scintigraphy ◽

Primary Tumor ◽

Bone Tumors ◽

Whole Body ◽

Skeletal Metastases ◽

Malignant Bone Tumors ◽

67Ga Scintigraphy ◽

Primary Bone Tumors ◽

Primary Bone

Whole-body scintigraphy with both 99mTc-phosphonate and 67Ga was performed on 92 patients suspected of primary bone tumors. In 46 patients with primary malignant bone tumors, scintigraphy with 99mTc-phosphonate disclosed the primary tumor in 44 cases and skeletal metastases in 11, and 67Ga scintigraphy detected the primary tumor in 43 cases, skeletal metastases in 6 cases and soft-tissue metastases in 8 cases. In 25 patients with secondary malignant bone tumors, bone scintigraphy visualized a single lesion in 10 cases and several lesions in 15 cases, and 67Ga scintigraphy detected the primary tumor in 17 cases, skeletal metastases in 17 cases and soft-tissue metastases in 9 cases. In 21 patients with benign bone disease positive uptake of 99mTc-phosphonate was recognized in 19 cases and uptake of 67Ga in 17 cases. It is concluded that bone scintigraphy should be used in patients suspected of primary bone tumors. If malignancy is suspected, 67Ga scintigraphy should be performed in addition.

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Prospective comparison of the diagnostic accuracy of 18F-FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients

European Radiology ◽

10.1007/s00330-021-07956-0 ◽

2021 ◽

Author(s):

Nils Martin Bruckmann ◽

Julian Kirchner ◽

Lale Umutlu ◽

Wolfgang Peter Fendler ◽

Robert Seifert ◽

...

Keyword(s):

Breast Cancer ◽

Bone Metastases ◽

Cancer Patients ◽

Bone Scintigraphy ◽

Fdg Pet ◽

Primary Breast Cancer ◽

Whole Body ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Initial Staging

Abstract Objectives To compare the diagnostic performance of [18F]FDG PET/MRI, MRI, CT, and bone scintigraphy for the detection of bone metastases in the initial staging of primary breast cancer patients. Material and methods A cohort of 154 therapy-naive patients with newly diagnosed, histopathologically proven breast cancer was enrolled in this study prospectively. All patients underwent a whole-body [18F]FDG PET/MRI, computed tomography (CT) scan, and a bone scintigraphy prior to therapy. All datasets were evaluated regarding the presence of bone metastases. McNemar χ2 test was performed to compare sensitivity and specificity between the modalities. Results Forty-one bone metastases were present in 7/154 patients (4.5%). Both [18F]FDG PET/MRI and MRI alone were able to detect all of the patients with histopathologically proven bone metastases (sensitivity 100%; specificity 100%) and did not miss any of the 41 malignant lesions (sensitivity 100%). CT detected 5/7 patients (sensitivity 71.4%; specificity 98.6%) and 23/41 lesions (sensitivity 56.1%). Bone scintigraphy detected only 2/7 patients (sensitivity 28.6%) and 15/41 lesions (sensitivity 36.6%). Furthermore, CT and scintigraphy led to false-positive findings of bone metastases in 2 patients and in 1 patient, respectively. The sensitivity of PET/MRI and MRI alone was significantly better compared with CT (p < 0.01, difference 43.9%) and bone scintigraphy (p < 0.01, difference 63.4%). Conclusion [18F]FDG PET/MRI and MRI are significantly better than CT or bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. Both CT and bone scintigraphy show a substantially limited sensitivity in detection of bone metastases. Key Points • [18F]FDG PET/MRI and MRI alone are significantly superior to CT and bone scintigraphy for the detection of bone metastases in patients with newly diagnosed breast cancer. • Radiation-free whole-body MRI might serve as modality of choice in detection of bone metastases in breast cancer patients.

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Detection and Segmentation of Pelvic Bones Metastases in MRI Images for Patients With Prostate Cancer Based on Deep Learning

Frontiers in Oncology ◽

10.3389/fonc.2021.773299 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xiang Liu ◽

Chao Han ◽

Yingpu Cui ◽

Tingting Xie ◽

Xiaodong Zhang ◽

...

Keyword(s):

Prostate Cancer ◽

Deep Learning ◽

Bone Metastases ◽

Model Development ◽

Whole Body ◽

Pelvic Bone ◽

Skeletal Metastases ◽

Dice Similarity Coefficient ◽

Patient Level ◽

Lesion Level

ObjectiveTo establish and evaluate the 3D U-Net model for automated segmentation and detection of pelvic bone metastases in patients with prostate cancer (PCa) using diffusion-weighted imaging (DWI) and T1 weighted imaging (T1WI) images.MethodsThe model consisted of two 3D U-Net algorithms. A total of 859 patients with clinically suspected or confirmed PCa between January 2017 and December 2020 were enrolled for the first 3D U-Net development of pelvic bony structure segmentation. Then, 334 PCa patients were selected for the model development of bone metastases segmentation. Additionally, 63 patients from January to May 2021 were recruited for the external evaluation of the network. The network was developed using DWI and T1WI images as input. Dice similarity coefficient (DSC), volumetric similarity (VS), and Hausdorff distance (HD) were used to evaluate the segmentation performance. Sensitivity, specificity, and area under the curve (AUC) were used to evaluate the detection performance at the patient level; recall, precision, and F1-score were assessed at the lesion level.ResultsThe pelvic bony structures segmentation on DWI and T1WI images had mean DSC and VS values above 0.85, and the HD values were <15 mm. In the testing set, the AUC of the metastases detection at the patient level were 0.85 and 0.80 on DWI and T1WI images. At the lesion level, the F1-score achieved 87.6% and 87.8% concerning metastases detection on DWI and T1WI images, respectively. In the external dataset, the AUC of the model for M-staging was 0.94 and 0.89 on DWI and T1WI images.ConclusionThe deep learning-based 3D U-Net network yields accurate detection and segmentation of pelvic bone metastases for PCa patients on DWI and T1WI images, which lays a foundation for the whole-body skeletal metastases assessment.

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Bone metastases in germ cell tumours: lessons learnt from a large retrospective study

BJU International ◽

10.1111/bju.12218 ◽

2013 ◽

Vol 112 (2) ◽

pp. 176-181 ◽

Cited By ~ 15

Author(s):

Mariam Jamal-Hanjani ◽

Anna Karpathakis ◽

Amy Kwan ◽

Danish Mazhar ◽

Wendy Ansell ◽

...

Keyword(s):

Retrospective Study ◽

Germ Cell ◽

Bone Metastases ◽

Germ Cell Tumours ◽

Lessons Learnt ◽

Large Retrospective Study

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Increased levels of XPA might be the basis of cisplatin resistance in germ cell tumours

BMC Cancer ◽

10.1186/s12885-019-6496-1 ◽

2020 ◽

Vol 20 (1) ◽

Cited By ~ 5

Author(s):

Zuzana Cierna ◽

Vera Miskovska ◽

Jan Roska ◽

Dana Jurkovicova ◽

Lucia Borszekova Pulzova ◽

...

Keyword(s):

Germ Cell ◽

Cell Lines ◽

Poor Prognosis ◽

Damage Identification ◽

Excision Repair ◽

Germ Cell Tumours ◽

Expression Levels ◽

Nucleotide Excision ◽

Visceral Metastases ◽

Prognosis Group

Abstract Background Germ cell tumours (GCTs) represent a highly curable malignity as they respond well to cisplatin (CDDP)-based chemotherapy. Nevertheless, a small proportion of GCT patients relapse or do not respond to therapy. As this might be caused by an increased capacity to repair CDDP-induced DNA damage, identification of DNA repair biomarkers predicting inadequate or aberrant response to CDDP, and thus poor prognosis for GCT patients, poses a challenge. The objective of this study is to examine the expression levels of the key nucleotide excision repair (NER) factors, XPA, ERCC1 and XPF, in GCT patients and cell lines. Methods Two hundred seven GCT patients’ specimens with sufficient follow-up clinical-pathological data and pairwise combinations of CDDP-resistant and -sensitive GCT cell lines were included. Immunohistochemistry was used to detect the ERCC1, XPF and XPA protein expression levels in GCT patients’ specimen and Western blot and qRT-PCR examined the protein and mRNA expression levels in GCT cell lines. Results GCT patients with low XPA expression had significantly better overall survival than patients with high expression (hazard ratio = 0.38, 95% confidence interval: 0.12–1.23, p = 0.0228). In addition, XPA expression was increased in the non-seminomatous histological subtype, IGCCCG poor prognosis group, increasing S stage, as well as the presence of lung, liver and non-pulmonary visceral metastases. Importantly, a correlation between inadequate or aberrant CDDP response and XPA expression found in GCT patients was also seen in GCT cell lines. Conclusions XPA expression is an additional independent prognostic biomarker for stratifying GCT patients, allowing for improvements in decision-making on treatment for those at high risk of refractoriness or relapse. In addition, it could represent a novel therapeutic target in GCTs.

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