Germ Cell Tumors Research Articles

Primary retroperitoneal lymph node dissection in testicular germ cell cancer in clinical stage IIA/B-renaissance of an established treatment?

The guideline-recommended treatment of choice for clinical stage IIA/B testicular germ cell tumors is chemotherapy with three cycles of PEB/four cycles of PE or, alternatively, radiation for seminomas. Despite their high curative efficacy, both options are associated with significant long-term toxicities. We evaluated the functional and oncological outcomes of primary retroperitoneal lymph node dissection (RPLND) as atherapeutic alternative. Between 2018 and 2022, 76patients (n = 34 seminomas, n = 42 nonseminomas) underwent primary RPLND for marker-negative clinical stage IIA/B testicular germ cell cancer. All patients underwent nerve-sparing RPLND with a unilateral or bilateral template dissection and had a follow-up ≥ 3months. None of the patients received adjuvant chemotherapy. In 24patients, the serum concentration of miR371a-3p was evaluated preoperatively. Follow-up was performed according to EAU guidelines. Median age and median follow-up were 30.1 (17-62)years and 29.3 (3-72)months, respectively. Mean operation time, blood loss, and duration of hospitalization were 131 (105-195) min, < 150 ml, and 4.5 (3-9) days, respectively. AClavien-Dindo IIIa complication was experienced by 8 (10.9%) patients. Antegrade ejaculation was preserved in 90.8%. Amean number of 19(7-68) lymph nodes were dissected. The mean number of positive lymph nodes was 1.1 (1-5), and the mean diameter of positive lymph nodes was 2.4 (0.8-4.6)cm. Eleven (14.5%) patients had stage pN0 (3/34 seminomas, 8/42 nonseminomas). In 24/27patients (88.9%) miR371 was positive, and it was negative in 4/4 with pN0 and 3/3 (100%) with teratoma. An outfield relapse was experienced by 7patients (9.2%), who then received salvage chemotherapy. Primary RPLND for marker-negative clinical stageIIA/B germ cell tumors results in high cure rates without adjuvant chemotherapy and is associated with alow rate of complications if performed in experienced hands. Therefore, primary RPLND should be included in the management of these patients.

Histopathological spectrum of ovarian tumours

Background: Ovarian neoplasms include wide spectrum of various tumors, which differ in their histo-morphological features, also in their biological behaviour, tumorigenesis, clinical course, and prognosis. Aim of the study was to study the histopathological features of various ovarian tumors and correlate preoperative serum CA125 tumor marker level with histopathological types. Also to study fallopian tubes for fallopian tube precursor lesions such as serous tubal intraepithelial carcinoma (STIC) in serous carcinoma ovary. Methods: This cross-sectional observational study of the 80 specimens of ovarian tumors was conducted in department of pathology, Netaji Subhash Chandra Bose medical college Jabalpur (M.P.). The relevant data of the patients was collected and analysed as per designed proforma. Results: Out of 80 cases; majority cases 22 (27.5%) were seen in a 31-40 years age group, followed by 41-50 years age group 18 cases (22.5%). Youngest patient was 7 years old and oldest patient was 88 years old, forming the range of 7 years to 88 years. Epithelial tumors were the most common category, followed by germ cell tumors, sex cord stromal tumors and metastatic tumors. Benign tumors were much higher than borderline and malignant tumors mature cystic teratoma was the most common tumor encountered, followed by mucinous cystadenoma. The commonest malignant tumor was serous carcinoma followed by mucinous carcinoma. Conclusions: Ovarian neoplasms constitute a wide spectrum of tumors therefore exact categorization is important to adopt appropriate treatment protocols for the proper management of the patient. Histopathological examination is the gold standard for diagnosis and categorization of ovarian neoplasm.

Characterization of testicular embryonic-type neuroectodermal tumor and embryonic-type neuroectodermal tissue admixed with mature neuro-glial tissue using a broad immunohistochemical panel.

Embryonic-type neuroectodermal tumor (ENT) is a somatic-type malignancy characterized by overgrowth of embryonic-type neuroectodermal tissue (EtNT). In germ cell tumors, EtNT is frequently intermingled with other components that may exhibit significant morphologic overlap [mature neuro-glial tissue (MNGT), nephroblastomatous tissues, and primitive endodermal-type glands]. Therefore, the quantification of EtNT (crucial for the diagnosis of ENT) can be challenging. In this study, we investigated the immunohistochemical profile of ENT, EtNT, and MNGT using a broad immunohistochemical panel. We found that SOX2 was the most sensitive marker for EtNT (100%), but it also stained MNGT (28.6%). GFAP and S100 were relatively sensitive (71.4%) and highly specific (GFAP 100%, S100 85.8%) for MNGT, whereas synaptophysin stained both. Combining our results with those of previous studies, we propose that a combination of SOX11, SOX2, GFAP, S100, AFP, villin, CDX2, PAX8, and nuclear WT1 may help to identify and quantify EtNT in germ cell tumors.

A deep learning model for differentiating paediatric intracranial germ cell tumour subtypes and predicting survival with MRI: a multicentre prospective study

BackgroundThe pretherapeutic differentiation of subtypes of primary intracranial germ cell tumours (iGCTs), including germinomas (GEs) and nongerminomatous germ cell tumours (NGGCTs), is essential for clinical practice because of distinct treatment strategies and prognostic profiles of these diseases. This study aimed to develop a deep learning model, iGNet, to assist in the differentiation and prognostication of iGCT subtypes by employing pretherapeutic MR T2-weighted imaging.MethodsThe iGNet model, which is based on the nnUNet architecture, was developed using a retrospective dataset of 280 pathologically confirmed iGCT patients. The training dataset included 83 GEs and 117 NGGCTs, while the retrospective internal test dataset included 31 GEs and 49 NGGCTs. The model’s diagnostic performance was then assessed with the area under the receiver operating characteristic curve (AUC) in a prospective internal dataset (n = 22) and two external datasets (n = 22 and 20). Next, we compared the diagnostic performance of six neuroradiologists with or without the assistance of iGNet. Finally, the predictive ability of the output of iGNet for progression-free and overall survival was assessed and compared to that of the pathological diagnosis.ResultsiGNet achieved high diagnostic performance, with AUCs between 0.869 and 0.950 across the four test datasets. With the assistance of iGNet, the six neuroradiologists’ diagnostic AUCs (averages of the four test datasets) increased by 9.22% to 17.90%. There was no significant difference between the output of iGNet and the results of pathological diagnosis in predicting progression-free and overall survival (P = .889).ConclusionsBy leveraging pretherapeutic MR imaging data, iGNet accurately differentiates iGCT subtypes, facilitating prognostic evaluation and increasing the potential for tailored treatment.Graphical

Unwrapping the immunological alterations in testicular germ cell tumors: From immune homeostasis to malignancy and emerging immunotherapies.

Testicular germ cell tumors (TGCTs), derived from primordial germ cells, are rare malignancies with high curative potential. However, the emergence of new evidence indicating that 15% of patients experience tumor progression, leading to death, underscores the need for innovative therapeutics. This review aimed to explore the immune status in maintaining testicular health and the immune-related aspects of malignancy. Furthermore, it presents an overview of current data on the use of immunotherapy for TGCT patients. Recent advances in immunology have opened a promising avenue for studying diseases and highlighted its role in treating diseases. While the immunopathological facets of TGCTs are not fully understood, investigations suggest a complex interplay among testis-resident immune cells, testis-specific cells (i.e., Sertoli cells (SCs) and Leydig cells (LCs)), and immune-regulating mediators (e.g., sex hormones) in the normal testicle that foster the testicular immune privilege (TIP). Although TIP plays a crucial role in sperm production, it also makes testis vulnerable to tumor development. In the context of cancer-related inflammation, disruption of TIP leads to an imbalanced immune response, resulting in chronic inflammation that can contribute to testicular tissue dysfunction or loss, potentially aiding in cancer invasion and progression. Comparing the immune profiles of normal and malignant testes is valuable and may provide insights into different aspects of testicular immunity and immune-based treatment approaches. For patients resistant to chemotherapy and with a poor prognosis, immunotherapy has shown promising results. However, its effectiveness in treating resistant TGCTs or preventing tumor recurrence is still uncertain.

Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease.

Paclitaxel, ifosfamide, and cisplatin (TIP) is an established salvage regimen for germ cell tumors (GCT) on the basis of a phase II trial, but efficacy on a large patient cohort including patients with unfavorable risk features and long-term outcomes has not been reported. Herein, we report updated treatment efficacy and long-term follow-up with TIP. Patients with GCT who received TIP after cisplatin-based chemotherapy were eligible. Favorable response (complete response or partial response with negative tumor markers), overall survival (OS) and progression-free survival (PFS) rates, relapse, and toxicity were determined. Disease was reclassified according to the International Prognostic Factor Study Group (IPFSG) score. Of the 104 patients, 87 had favorable risk factors and 17 had at least one unfavorable factor by Memorial Sloan Kettering Cancer Center (MSKCC) criteria. Ten patients were treated for a second gonadal primary GCT. With a median follow-up of 8.9 years, the 5-year PFS and OS rates were 66% (95% CI, 55 to 74) and 69% (95% CI, 59 to 77), respectively. Among 87 patients with favorable-risk disease, 69 (79%) achieved a favorable response with 5-year PFS and OS rates of 67% (95% CI, 56 to 76) and 72% (95% CI, 61 to 80), respectively. Among 17 patients with MSKCC unfavorable-risk disease, 13 (76%) achieved a favorable response with 5-year PFS and OS rates of 59% (95% CI, 33 to 78) and 56% (95% CI, 28 to 76), respectively. After IPFSG reclassification, 5-year PFS and OS rates for patients with ≤intermediate-risk disease were 75% (95% CI, 50 to 89) and 73% (95% CI, 55 to 85), respectively. TIP is an effective second-line regimen for patients with GCT. Similar outcomes were observed in patients with favorable- and unfavorable-risk disease. The randomized TIGER trial (ClinicalTrials.gov identifier: NCT02375204) comparing TIP with high-dose chemotherapy will determine the optimal second-line treatment approach.

A Case Report of Teratoma Trio: Bilateral Ovarian Teratomas Coexistent With a Mesenteric Teratoma

Teratomas arise from totipotent primordial cells and unveil a mixture of tissues of tri-dermal or bi-dermal origin. They are the most common ovarian germ cell tumors. The extragonadal teratomas may be seen in the sacrococcygeal region, mediastinum, retroperitoneum, and intracranially. These can be either mature, which are considered benign, or immature and classified as malignant. Mature cystic teratomas have characteristic imaging features and a pre-operative diagnosis that can be reliably made. The case provided was of a 48-year-old female who was diagnosed with three separate intraabdominal masses that had typical imaging features of teratomas. An extragonadal mesenteric teratoma is itself a rare entity and its coexistence with bilateral ovarian teratomas, has rarely been described in medical literature. Hence, common pathologies in an uncommon location should always be considered while providing a list of diagnostic differentials, in such a patient scenario.

Third ventricle teratoma with malignant transformation

Intracranial germ cell tumors(GCTs) are rare and heterogeneous group of primary brain tumors, mainly affecting pediatric population and young adults. The current understanding of the etiology of intracranial GCTs and their optimal management strategies remain controversial. Treatment plans differ depending on the subtype GCT and may vary among physicians and institutions. Central nervous system non-germinomatous germ cell tumor (NGGCT) usually requires surgical resection with histological verification, chemotherapy, and radiation. The extent of surgical resection is an important prognostic factor alongside the etiology and genetics of NGGCT. This article presents a rare clinical case of a rapidly growing teratoma located in the posterior part of third ventricle of a 17-year-old male presenting with symptoms of intracranial hypertension. Surgical total resection was preceded by endoscopic third ventriculostomy. Immunohistochemistry revealed the presence of embryonal carcinoma and immature teratoma cells turning the tumor into mixed type NGGCT with unfavorable prognosis. Despite the complete resection of the tumor and the timely initiation of adjuvant therapy, a rapid progression of the disease with subsequent unfavorable outcome was observed 3.6 months after the surgical treatment.

Clinical outcome and prognostic factors for immunotherapy-based treatments in patients with platinum-refractory germ cell tumor

BackgroundGerm cell tumors (GCTs) are a heterogeneous group of cancers associated with a favorable prognosis when treated with platinum-based chemotherapy. However, patients with platinum-refractory GCTs face limited options and poorer outcomes, necessitating innovative treatment approaches. This study aims to evaluate the clinical outcomes and identify prognostic factors associated with immunotherapy-based treatments in this challenging patient population. MethodsThis retrospective analysis included individuals with platinum-refractory GCTs treated with immunotherapy between 2017 and 2023. Clinical outcomes, safety, and biomarkers were analyzed. ResultsThe study included 37 male patients with a median age of 26 years (range: 18–65). The overall response rate was 24.32 %, with a median progression-free survival (PFS) and overall survival (OS) of 4.67 months and 22.67 months, respectively. Patients with both serum levels of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) below 100 (AFP & hCG < 100) demonstrated significantly better PFS and OS. Multivariate analysis indicated that lower serum tumor marker levels (AFP & hCG < 100) and treatment initiation at earlier lines were significantly associated with improved PFS. Notably, genomic analysis revealed that one patient with an MDM4 mutation experienced hyperprogression after the initiation of immunotherapy. Immune-related adverse events occurred in two patients: one developed grade 1 hyperthyroidism, and the other experienced grade 2 immune-related pneumonitis. ConclusionsImmunotherapy offers a promising treatment option for selected patients with platinum-refractory GCTs, demonstrating moderate response rates and potential survival benefits in a real-world scenario. Identifying specific prognostic factors may help tailor treatment strategies and enhance outcomes in this challenging patient cohort.

Suprasellar teratoma to germinoma recurrence: implications for diagnosis and follow-up.

Mature teratoma is a subtype of intracranial germ cell tumors (GCTs), distinguished from malignant GCTs by its benign nature and excellent prognosis. Typically, no adjuvant therapy is recommended following gross total resection (GTR). We report a case of a prepubertal girl with a suprasellar mature teratoma that recurred as a germinoma 6 months post-GTR. A 7-year-old girl presented with headache and polydipsia. Imaging revealed a suprasellar mass. The patient underwent GTR, and pathological diagnosis confirmed a mature teratoma without other GCT components. Six months later, MRI identified a newly developed suprasellar mass adjacent to the optic chiasm. A second surgery confirmed the mass as a germinoma. The patient subsequently underwent adjuvant chemotherapy combined with proton therapy, resulting in complete remission. The diagnosis of mature teratoma must be approached with caution, and thorough follow-up is imperative, particularly in cases involving female patients, prepubertal age, or non-pineal locations.

Primary yolk sac tumor of the endometrium combined with situs inversus totalis: a case report and literature review

BackgroundYolk sac tumor (YST) is a highly malignant germ cell tumor, a majority of which originate from the gonads and are extremely rare from endometrium.Case presentationHere we present a case of a 42-year-old woman suffered from primary pure yolk sac tumor of the endometrium complicated with situs inversus totalis. The patient presented at our hospital with irregular vaginal bleeding. Imageological examination showed a space-occupying lesion in the cervix and the serum Alpha-fetoprotein (AFP) level was significantly high (more than 1210ng/ml). Then she underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. The subsequent postoperative pathological diagnosis was yolk sac tumor arising from the endometrium. Next, the patient was treated with 6 cycles of chemotherapy with Pingyangmycin, etoposide and cisplatin regimen and was alive without evidence of recurrence or distant metastases for 13 months.ConclusionsThis rare disease needs to be differentiated from endometrial epithelial neoplasia and the significant increase in AFP is helpful for diagnosis. Combined with previous literature reports, comprehensive staging laparotomy or maximum cytoreductive surgery complemented by standard chemotherapy can usually achieve a good efficacy.

Embryoid Bodies and Related Proliferations in Ovarian Germ Cell Tumors.

We investigated the frequency and associated pathology of embryoid bodies in ovarian tumors by evaluating neoplasms in which they are known to occur: 100 immature teratomas, 125 malignant mixed germ cell tumors, and 6 polyembryomas. Three immature teratomas contained a single relatively well-formed embryoid body, whereas these and 11 others showed foci we categorized as embryoid body remnants consisting of microscopic aggregates of embryonal or yolk sac-type epithelium associated with spaces consistent with yolk sac or amniotic cavity but lacking a classic embryoid body structure. Teratomas with these foci were all high grade. A well-formed embryoid body was found in only 1 malignant mixed tumor, but embryoid body remnants were present in 25%, invariably associated with foci of immature teratoma (100%) and often with yolk sac tumor (97%), embryonal carcinoma (35%), or both (32%). These foci usually took the form of round to oval aggregates, often well-circumscribed, for which the term "polyembryoma background" has been proposed. The polyembryomas were typically grossly hemorrhagic and occurred in patients from 9 to 43 years of age. The embryoid bodies in them generally grew in lobules within an edematous to occasionally myxoid stroma. Four tumors contained liver-like cells, 4 numerous glands likely recapitulating the allantois, 3 syncytiotrophoblast cells, 2 prominent cysts, and 2 striking vascular proliferations. This study indicates that (1) typical embryoid bodies are rare in immature teratomas but about 14% of them have embryoid body remnants. (2) Embryoid body remnants are seen in 25% of malignant mixed germ cell tumors with a teratomatous component and often proliferate to form yolk sac tumor and embryonal carcinoma. (3) Well-formed embryoid bodies growing in a confluent manner (polyembryoma) are rare, and minor foci of teratoma, yolk sac tumor, or embryonal carcinoma are almost always present, indicating that these are fundamentally malignant mixed germ cell tumors but the polyembryoma component is dominant and distinctive which, in our opinion, justifies its own nomenclature. (4) Embryoid bodies are not a feature of other germ cell tumors.

“A Study To Assess The Effectiveness Of Planned Teaching Programme On Ovarian Germ Cell Tumor Among Adolescent Girls In A Selected College At Udaipur.”

Background Of The Study Adolescence is a transitional stage of physical and mental development generally occurring between puberty and legal adulthood, but largely characterized as beginning and ending with the teenage stage. Reaching girls during adolescence is critical decisions made and behaviors established during this period affect their horizons later in life. Many serious diseases in adulthood have their roots in adolescence. Germ cell tumors include a diverse group of tumors that arise from primitive germinal cells in either the gonads (ovaries, testicles).Germ cell tumors can occur almost anywhere in the body and can be either benign or malignant. Ovarian germ cell tumors are abnormal mass of tissue that forms in germ (egg) cells in the ovary. These tumors usually occur in teenage girls or young women, usually affect just one ovary and can be benign. Ovarian germ cell tumors represent 15 to 20 % of all ovarian tumors. They are rapidly growing neoplasm that arises from primordial germ cells derived from the embryo gonad. Of all gynecological tumors, ovarian malignancies represent the greatest clinical challenge. Ovarian cancer is the second most common malignancy of the female reproductive system and one of the leading causes of death among gynaecologic malignancies. Ovarian cancer represents a major surgical challenge requiring intensive and often complex therapies. It has the highest fatality-to-case ratio of all the gynaecological malignancies. Proper education is absolutely necessary in order to improve the adolescents’ knowledge. Early detection of ovarian germ cell tumor is essential to decrease the chances of complications. The aim of this study was to determine the effectiveness of planned teaching programme on ovarian germ cell tumor among adolescent girls in a selected college at Udaipur

701P Multicenter analysis of first-line (1L) regimens (BEP vs VIP) in patients (pts) with non-seminomatous germ cell tumors (NSGCTs) who subsequently underwent high-dose chemotherapy (HDCT)

701P Multicenter analysis of first-line (1L) regimens (BEP vs VIP) in patients (pts) with non-seminomatous germ cell tumors (NSGCTs) who subsequently underwent high-dose chemotherapy (HDCT)

706P Stereotactic radiosurgery (SRS) in brain metastases (BMs) from non-seminomatous germ cell tumours (NSCGTs)

706P Stereotactic radiosurgery (SRS) in brain metastases (BMs) from non-seminomatous germ cell tumours (NSCGTs)

Cut-offs for relapse detection in men with stage I testicular germ cell tumors during active surveillance within a prospective multicentre cohort study using either raw or housekeeper normalized miR-371a-3p serum levels

PurposeMiR-371a-3p represents a novel liquid biomarker that detects all histologies of germ-cell tumors (GCT) except teratoma. However, it is currently unclear whether miR-371a-3p results obtained directly from RT-PCR (raw Cq) or normalized for housekeeper genes and transformed into the relative quantity (RQ) value should be used and at what cut-off level. The purpose of this research was to evaluate, which values should be used, and a potential cut-off level for relapse-detection to inform subsequent studies. Materials and MethodsWe applied a CE-certified qRT-PCR test to measure miR-371a-3p at each follow-up visit during active surveillance in 34 men with stage I testicular GCT. MiR-371a-3p levels were calculated by the ΔΔ method. ResultsAbout 18 Patients had pure seminoma and 16 had mixed or nonseminomatous testicular GCT. Recurrences were detected in 10 patients and were correctly identified by both raw and housekeeper-normalized miR-371a-3p serum levels. The raw Cq, with a cut-off value of <28, resulted in only 1 false positive (3%), whereas RQ, with a cut-off value of >15, produced 6 false positive results (17%). Most of these false positive results normalized in subsequent measurements. The RQ approach detected recurrence in 1 patient 6 months earlier than the raw Cq approach. ConclusionOur preliminary data suggest that this CE-certified assay, using previously suggested cut-off values, is a promising method for detecting disease recurrence, provided a confirmatory second test is conducted to identify false positive results. To avoid unnecessary scans or overtreatment, we are currently validating this assay and cut-offs in a prospective cohort study.

707P Paclitaxel, ifosfamide and cisplatin (TIP) in patients (pts) with poor prognosis nonseminomatous germ cell tumor (NSGCT) with unfavourable serum tumor markers (STM) decline: A phase II study

707P Paclitaxel, ifosfamide and cisplatin (TIP) in patients (pts) with poor prognosis nonseminomatous germ cell tumor (NSGCT) with unfavourable serum tumor markers (STM) decline: A phase II study

Imaging of thymic epithelial tumors-a clinical practice review.

This review article comprehensively examines the diagnostic approach to thymic epithelial tumors (TETs) and other mediastinal masses, focusing on imaging modalities and differential diagnosis. Beginning with a discussion on traditional and contemporary classification systems for mediastinal tumors, including the Japanese Association for Research on the Thymus (JART) and International Thymic Interest Group (ITMIG) classifications, it highlights the shift towards computed tomography (CT)-based categorizations. Emphasis is placed on the importance of distinguishing between solid and cystic lesions in the anterior mediastinum, with detailed insights into imaging characteristics and histological features of various TET subtypes such as thymomas, thymic carcinomas, and thymic neuroendocrine tumors (NETs). The review also elucidates common differential diagnoses, including lymphomas and germ cell tumors, providing guidance on key imaging findings and considerations for accurate diagnosis. Furthermore, it underscores the significance of patient background and blood tests in differential diagnosis, discussing age-related prevalence patterns and tumor marker assessment. After addressing the diagnostic challenges posed by thymic cysts offering insights into their radiological features, management considerations, and potential complications, this review extends to other rare mediastinal lesions highlighting the need for a comprehensive evaluation for accurate identification and management of these tumors. Finally, as illustrative examples, we present six cases highlighting various aspects of anterior mediastinal tumors, including TET. These cases provide valuable insights into the diagnostic challenges, imaging characteristics, and management considerations encountered in clinical practice. The cases presented herein do not all illustrate typical images, courses, and diagnoses. However, they each contain significant implications. Thus, we present them with the belief that they will aid in understanding the intricate nuances of image diagnosis in actual clinical practice.

A prospective registry study of the epidemiology and management of childhood cancer in the Gambia-The first year experience.

Globally, over 180,000 children develop cancers yearly, with about 80% residing in low- or middle-income countries where cancer-associated mortality is also high. In The Gambia, cumulative incidence rate of 27.6 childhood cancers/million population was reported between 2002 and 2011. The current study appraised newly-established pediatric oncological services in The Gambia. In this prospective registry study, children with cancer who presented at the pediatric units, Edward Francis Small Teaching Hospital, Banjul, between November 2022 and October 2023 were assessed. Data on sociodemographic variables, mode of admission and presentation, tumor type, diagnostic methods, and challenges such as laboratory support, treatment, use of blood/blood products; and eventual outcome were analyzed. The median (interquartile range, IQR) age at presentation of the 44 children was 36.0 (22.3-117.0) months. Wilms tumor was the most common tumor 12 (27.3%); followed by leukemia 11 (25.0%); germ cell tumor 8 (18.2%); lymphoma 6 (13.6%); retinoblastoma 4 (9.1%); rhabdomyosarcoma 2 (4.5%) and one central nervous system tumor (2.3%). The median(IQR) duration of symptoms before presentation was 48 (21-90) days, presentation to diagnosis 7.5 (3-20.8) days, and first symptom to diagnosis 62.5 (32-126.8) days. Treatment refusal and abandonment rates were 20.5% and 13.6%, respectively. Families of 93.8% of children could not procure cytotoxic drugs due to nonavailability, high cost, or both. Adequate laboratory monitoring was only available in 6.8%, and none had platelet concentrate transfusion or radiotherapy. The nine (20.5%) who completed treatment are currently being followed up, 10(22.7%) are still receiving chemotherapy, while 2(4.5%) were referred. Eight (18.2%) died, predominantly from metastasis (75%) and severe drug toxicities (25%). Late presentation and diagnosis, poverty, unavailability of drugs, suboptimal or lack of laboratory testing, blood product, adjuvant medications, and psychosocial supports contributed to high treatment refusal, abandonment, and mortality. These daunting challenges can be ameliorated with regular community sensitization, frequent cancer auditing, and strong political will.

700P Detection of circulating tumor DNA and chromosome 3p25.3 gain in relapsed/refractory germ cell tumors and impact of salvage high-dose chemotherapy: Results from the Italian Germ Cell Cancer Group 04 study

700P Detection of circulating tumor DNA and chromosome 3p25.3 gain in relapsed/refractory germ cell tumors and impact of salvage high-dose chemotherapy: Results from the Italian Germ Cell Cancer Group 04 study