Bleomycin, Etoposide And Cisplatin Research Articles

P-088 Bleomycin, etoposide and cisplatin (BEP) chemotherapy-induced testicular toxicity: ameliorative effect of sodium alginate by inhibiting oxidative stress, apoptosis and inflammation

Abstract Study question Is there a potential for sodium alginate (NaAL) to alleviate the damage induced by BEP chemotherapy in testicular cells and the spermatogenesis process? Summary answer Administering NaAL at doses of 25 and 50 mg/kg demonstrates protective effects against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, inflammation, and apoptosis. What is known already Testicular tumours are a prevalent malignancy affecting young males aged 20 to 35 years. The globally accepted chemotherapy for testicular cancer involves administering the bleomycin, etoposide, and cisplatin (BEP) regimen in three to four cycles. Unfortunately, the BEP regimen poses a substantial risk of reproductive system toxicity, presenting a significant concern and one of the most challenging long-term complications for young cancer survivors. Sodium alginate (NaAL), an anionic polysaccharide abundant in nature, offers potential solutions with its inherent antioxidant, anti-inflammatory, anti-apoptotic, and anti-proliferative properties. Study design, size, duration Sixty adult male Wistar rats were randomly assigned to six groups (n = 10/group). Groups 1, 3, and 4 received a vehicle, 25 mg/kg, and 50 mg/kg of NaAL, respectively. The remaining groups underwent a three-week cycle of bleomycin, etoposide, and cisplatin (BEP) with or without NaAL. NaAL administration began one week before BEP initiation, continued on days 2, 9, and 16, and extended for one week post the BEP cycle. Participants/materials, setting, methods At the end of the study (day 42), various parameters, including body and testes weight, sperm parameters (count, motility, viability, and morphology), testosterone hormone levels, testicular histopathology, stereological parameters of the testes, and levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), were assessed. Additionally, the expression of Bcl-2, Bax, caspase-3, p53, and TNF-α was evaluated using real-time PCR and immunohistochemistry. Main results and the role of chance NaAL treatment resulted in a significant improvement in both body weight and testis weight in animals injected with BEP compared to the BEP group (P < 0.05). Stereological procedures, QRT-PCR examination, and immunohistochemical (IHC) staining for quantitative testis analysis indicated that NaAL reversed the impaired spermatogenesis induced by BEP (P < 0.05). Additionally, NaAL restored the disturbance caused by BEP in sperm count, motility, viability, and morphology. The testosterone level significantly decreased in the BEP-treated group compared to the control group (P < 0.05). However, co-administration of 50 mg/kg of NaAL significantly increased the serum testosterone level (P < 0.05). Furthermore, NaAL improved the antioxidant status of the testis by increasing TAC and ameliorating MDA and NO levels. Notably, QRT-PCR examination revealed that NaAL treatment suppressed BEP-induced apoptosis and inflammation by modulating genes such as Bcl-2, Bax, Caspase-3, and p53 in the testis (P < 0.05). Co-administration of 25 and 50 mg/kg of NaAL with the BEP regimen significantly reduced the number of p53 and TNF-α-positive cells compared to the BEP group. Further, NaAL at low and high doses increased the expression of Bcl-2 protein in spermatogenic cells compared to the BEP-treated group. Limitations, reasons for caution Due to limitations in our laboratory resources, we were unable to pursue further studies to validate the mechanism of sodium alginate on specific targets using more advanced techniques such as transfection and transgenic methodologies. Wider implications of the findings These findings illuminate the potential clinical applications of sodium alginate, suggesting its promising role as a beneficial supplement in medical contexts, particularly in addressing fertility issues. Additionally, this antioxidant could accelerate the fertility recovery period in young patients undergoing the BEP chemotherapy regimen, ultimately enhancing their overall quality of life. Trial registration number N/A

Therapeutic effect of sodium alginate on bleomycin, etoposide and cisplatin (BEP)-induced reproductive toxicity by inhibiting nitro-oxidative stress, inflammation and apoptosis

Impaired spermatogenesis and male infertility are common consequences of chemotherapy drugs used in patients with testicular cancer. The present study investigated the effects of sodium alginate (NaAL) on testicular toxicity caused by bleomycin, etoposide, and cisplatin (BEP). Rats in group 1 received normal saline, while groups 2 and 3 were treated with 25 and 50 mg/kg of NaAL, respectively. Group 4 was treated with a 21-day cycle of BEP (0.5 mg/kg bleomycin, 5 mg/kg etoposide, and 1 mg/kg cisplatin), and groups 5 and 6 received BEP regimen plus 25 and 50 mg/kg of NaAL, respectively. Then, sperm parameters, testosterone levels, testicular histopathology and stereological parameters, testicular levels of malondialdehyde (MDA), nitric oxide (NO), and total antioxidant capacity (TAC), and the expression of apoptosis-associated genes including Bcl2, Bax, Caspase3, p53, and TNF-α were evaluated. Our findings revealed that NaAL improved sperm parameters, testosterone levels, histopathology, and stereology parameters in BEP-administrated rats. NaAL also improved testis antioxidant status by enhancing TAC and ameliorating MDA and NO. Further, modifications to the expression of Bcl2, Bax, Caspase3, p53, and TNF-α suggested that NaAL alleviated BEP-induced apoptosis and inflammation. Collectively, NaAL protects rats’ testes against BEP-evoked toxicity damage through the modulation of nitro-oxidative stress, apoptosis, and inflammation.

Antiemetic Efficacy and Safety of Palonosetron on Days 1 and 5 with Aprepitant and Dexamethasone during Bleomycin, Etoposide, and Cisplatin Chemotherapy in Patients with Germ Cell Tumor: A Prospective Study

Objective. BEP (bleomycin, etoposide, and cisplatin) chemotherapy is a standard regimen for germ cell tumors (GCTs); however, their high emetogenicity is problematic. The control of chemotherapy‐induced nausea and vomiting (CINV) is crucial to complete the treatment. We conducted this study to explore the efficacy and safety of antiemetic therapy with dexamethasone and aprepitant for 5 days in combination with palonosetron 0.75 mg on days 1 and 5 in BEP. Methods. This open‐label single‐arm study was prospectively conducted in 4 hospitals. Chemotherapy‐naïve men with GCT who were scheduled to receive the BEP regimen were eligible. The primary endpoint was the complete response (CR) rate of CINV. Results. A total of 19 patients were enrolled. Overall, 16 (84.2%) patients experienced some nausea, whereas only 4 (21.1%) patients had grade 1 emetic events. Overall CR of CINV was achieved in 9 (47.4%) patients. Although 14 (73.7%) patients experienced 22 adverse events after palonosetron administration, severe adverse events (grade 3 or more) attributable to it did not occur. Conclusion. The results suggest that aprepitant, palonosetron, and dexamethasone antiemetic therapy for patients with GCT receiving BEP is safe, whereas the efficacy of additional palonosetron administration on day 5 for prevention of delayed CINV remains unclear. This trial is registered with UMIN000008110.

THU509 Tapping Into The Potential Of Social Media To Understand Treatment Experiences Of Survivors Of Rare Cancers: Findings From The Granulosa Cell Tumor (GCT) Survivor Sisters Facebook® Group Member Survey

Abstract Disclosure: S. Chu: None. V.M. White: None. M. Alexiadis: None. K. Eroh: None. K. Ackermann: None. S. Rodgers: None. L.M. Langdale: None. N.E. Armour: None. T.W. Jobling: None. P.J. Fuller: None. Background: Engaging with online social media consumer groups for rare cancers may help to develop collaborations between consumers and researchers. This study, a collaboration with the Granulosa Cell Tumour-Survivor Sisters (GCT-SS) Facebook® group, explores the results of their survey of member’s treatment and follow-up experiences. Method: Members of the closed multinational GCT-SS Facebook® group completed a 43-item survey covering symptoms, diagnosis, treatment, recurrence, follow-up, and possible risk factors for GCT. Group members had either adult (aGCT) or juvenile (jGCT) disease. Data was collected via an online survey between 2014 and 2019. Open-ended responses were reviewed by the study team and coded into agreed categorical responses or binary-type variables. Statistical analysis was conducted using SPSS V28. Descriptive statistics (e.g. frequencies) were used to describe the sample in terms of individual, disease and treatment characteristics. Pearson Chi-square or Fisher’s exact test were used to compare proportions between groups (e.g., recurrence or not). Logistic regression was used to examine factors associated with recurrent disease. Results: 744 members (average 4.4 years (SD=5.9) post-diagnosis) participated including 52 with jGCT. 67% had stage I disease and 8% stage III–V at diagnosis, although 30% of aGCT and 25% of jGCT reported recurrent disease at survey completion. 48% of aGCT had laparoscopic surgery, tumor encapsulation was reported by 49% and tumor bagging reported by 29% overall (37% laparoscopic; 8% open). Recurrence rates were higher when the tumor was cut or ruptured (ruptured: p<.001; cut: p=.01). 19% of aGCT had chemotherapy with this most common for stage II-III disease. BEP (bleomycin, etoposide and cisplatin) protocols became less common over time (diagnosed < 2015: 47% vs diagnosed post-2015: 21%). Conclusions: While there is a growing recognition of the need for involvement of patients and the public across the entire research process, to date consumer involvement has mainly focused on setting research questions/focus and recruitment. The development of information and support groups on social media platforms has provided a unique opportunity for greater collaboration between consumers, researchers and clinicians. This may be of particular benefit when the disease is rare as the global reach of these platforms allows relatively large numbers of people with the condition to connect. Our study suggests the feasibility of engaging with communities that have developed via social media platforms. Members of the GCT-SS group report treatment patterns generally in line with those found from clinical audits. Utilising naturally forming consumer groups may assist with developing the evidence base for care and supporting those living with GCT ovarian cancer. Presentation: Thursday, June 15, 2023

TANDEM HIGH DOSE CHEMOTHERAPY WITH AUTOLOGOUS BONE MARROW TRANSPLANTATION IN GERM CELL TUMOR— EXPERIENCE FROM A TERTIARY CARE CENTER FROM SOUTH INDIA

Background: The use of high-dose chemotherapy with autologous hematopoietic cell transplantation is well established as a potentially curative approach in patients with relapsed or refractory disease in testicular Germ cell tumours after initial cisplatin-based chemotherapy. The use of tandem transplant with high-dose carboplatin and etoposide conditioning has been a tried and is a feasible option in relapse setting.Overall, HDCTand Autologous stem cell transplant can offer cure rates of up to 60% in the relapsed GCTsetting. Data on Tandem HDCTand ASCTis very limited in Indian subcontinent. Hence we report our experience with respect to safety, efcacy and tolerability, survival outcomes of HDCT/ ASCT in patients with relapsed GCT. Methods: Patients who were diagnosed with relapsed or refractory Germ cell tumours and underwent Tandem HDCT and ASCT were analysed from patient records from 2013 to 2020. Results: Both our patients received BEP (bleomycin, etoposide, and cisplatin) as rst-line therapy. HDCT was done after 2nd line salvage chemotherapies in both patients. Both patients were treated with 2 courses of High-dose carboplatin (700mg/m2) and etoposide(750mg/m2) as conditioning regimen followed by stem cell rescue(CD34+ stem cells yield – 5 to 6x106 cells/kg ) 3-4 weeks apart. Grade ¾ toxicities including myelosuppression, diarrhea, mucositis were observed in both patients. After ASCT both patients were followed up with imaging and serial monitoring of tumour markers. 1st patient died 3 months after ASCT due to disease relapse and our 2nd patient was disease free for 22 months, after which he developed progressive disease in brain and succumbed to disease. Conclusion: This is the rst report from India on tandem HDCT with ACST in relapsed GCTs. Tandem HDCT/ASCT seems to be safe and feasible option in relapsed/ refractory testicular GCT's.

535P Long term quality of life after chemotherapy among nonepithelial ovarian cancer survivors: The case-control vivrovaire rare tumours study

Treatments (ttt) of non-epithelial rare germ cell tumors (GCT) and sex cord stromal tumors (SCST) are associated with long survival. The standard treatment mainly includes conservative surgery combined with chemotherapy (CT) [bleomycin, etoposide and cisplatin (BEP)] depending on stage and prognostic factors. As reported in testicular cancer survivors, BEP may induce late side effects with negative impact on quality of life (QOL). The French Rare Malignant Gynecological Tumors (TMRG)/GINECO case-control VIVROVAIRE Rare tumors study assessed long term QOL among survivors treated with BEP as compared to age-matched healthy women (HW). Non-epithelial ovarian cancer survivors (nEOCS), cancer-free ≥2 years after end of treatment, were identified from the INCa French Network for TMRG. HW were issued from the ‘Seintinelles’ research platform. QOL (FACT-G and FACT-O), chronic fatigue (MFI), anxiety/depression (HADS), insomnia (ISI), neurotoxicity (FACT/GOG-NTX), cognition (FACT-COG) and sexuality items (from the FACT-O OCS) were compared between nEOCS and HW. A minimal 5% difference for the score between groups was considered as clinically relevant. 144 nEOCS were included with 144 age-matched HW (mean age at inclusion: 38 yrs; 60% aged below 40). Most nEOCS were treated for GCT (n=112). Median delay from the end of ttt to inclusion was 6 yrs. At inclusion, 42% of nEOCS were menopausal versus 17% of HW (p<0.001). General and ovarian QOL, fatigue, anxiety/depression and insomnia scores were similar between nEOCS and HW. nEOCS reported clinically significant (6%) better social functioning (p=0.006). However, nEOCS reported more perceived cognitive impairment than HW (31 vs 14%, p<0.001) and clinically significant (8%) neurotoxicity (p<0.001). In addition, nEOCS reported less interest in sex (35% vs 55%, p<0.001), felt less like a woman (67% vs 81%, p=0.012), and were more afraid of not having children (31% vs 13%, p=0.007) than HW, whatever the menopausal status. 6 yrs after BEP CT, most of nEOCS reported similar global QOL as HW, but experienced more risk of premature menopause, some late side effects on cognition, neurotoxicity and sexuality that may impact their daily life.

Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer

PurposeClinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS.MethodsData from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher’s exact and Chi-square test.ResultsOut of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death.ConclusionAround 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

Outcomes of retroperitoneal lymph node dissection for testicular cancer by a high volume surgeon from Australia: a case for centralisation.

There are few studies examining retroperitoneal lymph node dissection (RPLND) for testicular cancer in Australia. This study examines the perioperative outcomes, complications and survival rates following RPLND, by a high volume, single surgeon. A retrospective, case series of a single surgeon, multi-centre study included all patients who underwent RPLND following testicular cancer at Westmead Public Hospital, Westmead Private Hospital, and Macquarie University Hospital 2005-2020. One hundred one patients identified, with 94 having sufficient available data. At time of operation, median age was 29.5 years. 84.2% had T1 or T2 primary tumours at diagnosis. Most common RPLND indication was residual mass post-chemotherapy (92.6%), with bleomycin, etoposide and cisplatin (BEP)x3 and BEPx4 most common chemotherapy regimens (50% and 35% respectively). Post-chemotherapy, largest residual mass ranged from 0.9 to 20 cm (median 3.32 cm). Post-chemotherapy, 95.7% masses were found in retroperitoneum (64.4% para-aortic region). 93.6% had open approach. 42.5% had bilateral nerve sparing. Majority (97.1%) did not require blood transfusion. No complications reported in 52.1% of patients. No deaths recorded within 90 days of surgery. At time of analysis, 91.5% had recurrence free survival, and 92.6% overall survival, at a median follow-up since surgery of 47.5months (range 11 to 200 months). This retrospective study, addressing peri-operative surgical outcomes for RPLND surgery in Australia, is comparable to high-volume international urological centre studies, and shows that centralisation of post-chemotherapy RPLND to an experienced surgeon, results in low perioperative morbidity and mortality.

\u201cChronic fatigue, quality of life and long-term side-effects of chemotherapy in patients treated for non-epithelial ovarian cancer: national case-control protocol study of the GINECO-Vivrovaire rare tumors INCa French network for rare malignant ovarian tumors\u201d

BackgroundGerm cell tumors and sex cord stromal tumors are rare cancers of the ovary. They mainly affect young women and are associated with a high survival rate. The standard treatment mainly involves conservative surgery combined with chemotherapy [bleomycin, etoposide and cisplatin (BEP)] depending on the stage and the prognostic factors, as for testicular cancers. As reported in testicular cancer survivors, chemotherapy may induce sequelae impacting quality of life, which has not yet been evaluated in survivors of germ cell tumors and sex cord stromal tumors. The GINECO-VIVROVAIRE-Rare tumor study is a two-step investigation aiming to assess i) chronic fatigue and quality of life and ii) long-term side-effects of chemotherapy with a focus on cardiovascular and pulmonary disorders.MethodsUsing self-reported questionnaires, chronic fatigue and quality of life are compared between 134 ovarian cancer survivors (cancer-free ≥2 years after treatment) treated with surgery and chemotherapy and 2 control groups (67 ovarian cancer survivors treated with surgery alone and 67 age-matched healthy women). Medical data are collected from patient records. In the second step evaluating the long-term side-effects of chemotherapy, a subgroup of 90 patients treated with chemotherapy and 45 controls undergo the following work-up: cardiovascular evaluation (clinical examination, non-invasive cardiovascular tests to explore heart disease, blood tests), pulmonary function testing, audiogram, metabolic and hormonal blood tests. Costs of sequelae will be also assessed. Patients are selected from the registry of the INCa French Network for Rare Malignant Ovarian Tumors, and healthy women by the ‘Seintinelles’ connected network (collaborative research platform).DiscussionThis study will provide important data on the potential long-term physical side-effects of chemotherapy in survivors of Germ Cell Tumors (GCT) and Sex Cord Stromal Tumors (SCST), especially cardiovascular and pulmonary disorders, and neurotoxicity. The identification of long-term side-effects can contribute to adjusting the treatment of ovarian GCT or SCST patients and to managing follow-up with adapted recommendations regarding practices and chemotherapy regimens, in order to reduce toxicity while maintaining efficacy. Based on the results, intervention strategies could be proposed to improve the management of these patients during their treatment and in the long term.Trial registrationThis trial was registered at clinicaltrials.gov: 03418844, on 1 February 2018.This trial was registered on 25 October 2017 under the unique European identification number (ID-RCB): 2017-A03028–45.Recruitment Status: Recruiting.Protocol versionVersion n° 4.2 dated from Feb 19, 2021.Trial sponsorCentre François Baclesse, 3 avenue du Général Harris, F-14076 Caen cedex 05, France.

Surgery for lung metastases in a testicular seminoma

Abstract Invasive testicular cancer develops from carcinoma in situ (CIS)/testicular intraepithelial neoplasia (TIN), and these histological types are often identified in residual non-malignant testicular tissues. The objective was to highlight the need for an immediate multidisciplinary approach in a case of seminoma with lung metastases in a young patient, to approach optimal therapeutic behaviour. We present the case of a 33-year-old patient, a smoker, who presents with an influenced general condition, bilateral crackling rales, the right testicle slightly enlarged in volume. Emergency chest radiography raises suspicion of lung metastases. Computed tomography (CT) sustains the suspicion of secondary malignancies, which is why the pulmonary formation is approached endobronchial, having as a histopathological result seminoma metastasis. Blood tests, before urological intervention show an alpha-fetoprotein (AFP) = 11.05 mUI/mL, beta human chorionic gonadotropin (hCG) = 20.47 mUI/L, lactate dehydrogenase (LDH) = 754 U/L, subsequently performing right radical orchiectomy (2016), pT1N3M1a-stage IIIB. Repeating the blood tests after the fourth chemotherapy session [bleomycin, etoposide and cisplatin (BEP)] reveals a normalisation of AFP = 0.4 mUI/mL, beta hCG &lt; 0.1 mUI/L, LDH = 276 U/L results, and at positron emission tomography-computed tomography (PET-CT) examination the pulmonary tumour formations were not metabolically active. Subsequently, lung metastases were removed by laser surgery (2020), with significant resorption and preservation of healthy lung parenchyma, and is classified according to the TNM8 staging in stage IV-pT3N0M1a. The particularity of this case was the multiple pulmonary secondary malignancies, which, although imagistically persisted, were not metabolically active, and is interpreted as remainings after oncological treatment. Considering the modifications, the advanced stage and the estimated prognosis, the case can be summarised as a therapeutic success.

Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection – A 13-year follow-up analysis of a phase III trial cohort

BackgroundOne cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up. MethodsQuestionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75). ResultsWith a median follow-up of 13.8 years (0–22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96–100%)/92% (CI 89–99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87–97%)/93% (CI 86–97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01). ConclusionsWith long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.

Autologous Stem Cell Transplantation in Testicular Germ Cell Tumor-Preliminary Experience from a Single Center.

Background Germ cell tumor (GCT) of the testis is one of the highly curable solid organ malignancies. Those who experience relapse after platinum-based chemotherapy can be salvaged with systemic therapy followed by high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT). Complete remission can be obtained in approximately 50 to 60% of patients treated with HDCT. Our experience reports the efficacy and safety of HDCT followed by ASCT in relapsed GCT. Methods Analysis of patient records (2012–2019) showed that three patients had received HDCT and ASCT. Results All the three patients were treated with BEP (bleomycin, etoposide, and cisplatin) as first-line therapy. HDCT was done in Case 1 after third-line salvage and in other two patients after second-line salvage chemotherapies. High-dose carboplatin and etoposide were used as conditioning regimen. Granulocyte colony-stimulating factor was used for the mobilization of stem cells. After ASCT, complete remission was documented in all the patients. All were alive and disease-free till the last follow-up. Grade ¾ toxicities including myelosuppression, diarrhea, and mucositis were observed in all three patients. Conclusion This is the first report from India on HDCT with ASCT in GCT. HDCT/ASCT seems to be feasible, safe, and effective in relapsed testicular GCTs.

What mind does not know eyes cannot see!! – A case of bleomycin-induced flagellate hyperpigmentation

Recognition of cutaneous side effects of bleomycin, a commonly used chemotherapeutic agent, is important to avoid unnecessary discontinuation of therapy. Here, we present the case of a 15-year-old boy who was undergoing treatment with standard BEP (bleomycin, etoposide, and cisplatin) regime, presented with flagellate hyperpigmented lesions in the back, arm, and thighs.

Primary mediastinal germ cell tumours: real world experience in the low middle income (LMIC) setting.

PurposePrimary mediastinal germ cell tumours (PMGCTs) are rare; with limited data available about their outcomes and optimal treatment in the low middle income countries setting. We studied the clinical profile of patients with PMGCT treated at our centre in order to estimate their survival outcomes and to identify prognostic factors affecting the same.Patients and methodsFifty-seven patients with PMGCTs treated between April 2001 and June 2019 were included. Baseline characteristics, details of first line chemotherapy, response rates, toxicity and surgical outcomes were noted. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method.ResultsAmong 57 male patients (seminoma = 20 and nonseminomatous = 37), the median follow-up was 10 months (range: 1–120 months). For mediastinal seminoma, 9 (45%) and 11 (55%) patients had good and intermediate risk disease, respectively. Nineteen patients (95%) received BEP (Bleomycin, etoposide and cisplatin) chemotherapy. 94.7% had partial responses and median event-free survival was not reached. All patients were alive and disease free at 2 years. For primary mediastinal nonseminomatous germ cell tumours (PMNSGCTs), all patients were poor risk. Thirty-four (91.8%) received BEP/EP chemotherapy as first line. Responses were PRM+ (partial response with elevated markers) in 7 (20.5%) and PRM− in 12 (35.2%). The incidence of febrile neutropenia was 50% and 55.8% in seminole and PMNSGCT, respectively. The median OS was 9.06 months and median PFS was 4.63 months for PMNSGCT. The proportion of patients alive at 1 year and 2 years were 35% and 24.3%, respectively.ConclusionPrimary mediastinal seminomas are rarer and have better survival outcomes. Treatment of PMNSGCT is still a challenge and is associated with poorer survival outcomes.

An extragonadal germ cell tumor with dermatomyositis: A case report and literature review.

The risk of malignancy in inflammatory myopathy patients is well recognized. However, the incidence of germ cell tumor (GCT) with inflammatory myopathy is low, and most reported cases of GCT also exhibit testicular tumors. Therefore, a case of extragonadal GCT with dermatomyositis (DM) is reported in the current study to better understand this paraneoplastic syndrome. A 53-year-old man presented with bilateral cervical lymph node enlargement. A lymph node biopsy showed embryonal carcinoma, and computed tomography showed multiple lymph node and lung metastases. A period of one month after bleomycin, etoposide and cisplatin (BEP) chemotherapy, this patient developed an erythematous eruption over the extensor surfaces of bilateral fingers, or Gottron's sign and facial erythema. The patient was diagnosed with DM with a positive anti-TIF-1γ-antibody result. High-dose prednisolone was effective, and there has been no evidence of cancer recurrence for over one year. The literature review identified 17 cases of GCT with inflammatory myopathy that have been reported so far, and it was indicated that this is the first case of extragonadal GCT with DM following chemotherapy. This case highlights the importance of monitoring after the completion of cancer treatment, as distinctive dermal and muscular symptoms should cause us to consider the possibility of paraneoplastic inflammatory myopathy.

Neutropenic sepsis rates in patients receiving bleomycin, etoposide and cisplatin chemotherapy using olanzapine and reduced doses of dexamethasone compared to a standard antiemetic regimen.

To investigate whether the use of a steroid-sparing antiemetic protocol (substituting dexamethasone with olanzapine) affects the incidence of neutropenia and associated hospital admissions in patients receiving bleomycin, etoposide and cisplatin (BEP) chemotherapy. Records from 108 patients who received BEP at St Bartholomew's Hospital, London were divided into two groups according to antiemetic regimen. Group 1 (treated 2008-2013) were treated with a steroid-containing antiemetic protocol and group 2 (treated 2014-2017) were treated according to a steroid-sparing protocol, i.e. using olanzapine. Outcomes included incidence of neutropenia at nadir blood count, severity of neutropenia, hospital admissions attributable to febrile neutropenia (FN) and baseline risk factors associated with FN. Statistical analyses were performed using two-sided chi-squared tests. The baseline characteristics of the two groups were balanced with regard to age, gender, histology, and proportion of patients with International Germ Cell Cancer Collaborative Group poor-risk disease. The incidence of neutropenia of any grade (group 1, 96.2%; group 2, 98.1%) was similar, although group 2 had more patients with severe neutropenia than group 2 (77.7% vs 88.8%). There was a significant difference in FN incidence (group 1, 22%; group 2 7.5%; P=0.030). Most cases of FN occurred in cycle 1. Two baseline characteristics were over-represented in patients who developed FN: female sex and age ≥50years. By comparing two cohorts who received prophylactic antibiotics, our audit suggests that rates of FN-related admissions were lower in the cohort of patients in whom we employed a steroid-sparing antiemetic protocol.

Multicenter analysis of serum tumor markers, treatment patterns, and relapse in patients with testicular cancer in clinical stage IS.

5052 Background: Testicular germ cell tumors (TGCT) in clinical stage I (CSI) are tumors confined to the testis without evidence of metastasis. Around 50% of all TGCT patients present with elevated serum tumor markers (TM) such as alpha-feto protein (AFP), beta-humanochoriongonadotropin (ß-HCG) and lactate-dehydrogenase (LDH). After ablatio testis, TMs usually return to normal according to half-life kinetics, however, in clinical stage IS (CSIS) TMs remain elevated or increase after surgery. Follow-up data on CSIS is scarce and our study aims to assess clinical characteristics and oncologic outcomes in a large TGCT cohort. Methods: In this multicenter study we collected data from 5 tertiary referring hospitals in Germany, included patients with CSIS and evaluated TM levels, treatment and the primary outcome relapse-free survival. False CSIS was defined as documented CSIS but TMs that returned to normal after respective half-life kinetics. Differences between predefined groups (chemotherapy, TM, true/false CSIS) was analyzed with fisher’s exact and chi-square test. Results: Overall, 2616 patient data files were analyzed. Forty-three patients (1.6%) were documented as CSIS of which 27 (63%) were true and 16 (37%) false CSIS. Six (14%) had seminomas and 37 (86%) non-seminomas. In the true CSIS group AFP, ß-HCG, AFP plus ß-HCG and LDH were elevated in 13, 6, 3 and 2 cases. Four true CSIS patients received surveillance, 21 had 3x or 2x courses of BEP (bleomycin, etoposide and cisplatin) and 2 carboplatin. Within the false CSIS group, 2 patients were treated with surveillance, 10 received 3x BEP, one 3x PEI (cisplatin, etoposide and ifosfamid) and 3 had carboplatin. Chi-Square test revealed no difference between true or false CSIS classification in respect to application of chemotherapy (any chemotherapy, p = 0.83). Relapse-free survival after 5 and 10 years was 88.9% and 77.8%, respectively. Three patients in the true CSIS group relapsed (2 seminomas had carboplatin, 1 non-seminoma had surveillance). All relapses were treated with 3 courses of BEP with no documented death in the CSIS population. Conclusions: Overall, less than 2% of all TGCT were documented CSIS of which 37% were falsely classified. We report a high proportion of relapse-free survival in CSIS treated with surveillance or BEP with a high heterogeneity in treatment patterns. Correct classification of CSIS remains of critical importance to avoid toxicity for patients that could be safely treated with surveillance.

Prognostic role of early interim [18F] fluoro-deoxy-glucose positron emission tomography in patients with advanced seminoma undergoing standard treatment.

5055 Background: In patients (pts) with advanced seminoma, efforts are underway to tailor a risk-adapted treatment strategy to the individual pt. Our main objective was to prospectively determine the prognostic value of [18F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT2) after two cycles of bleomycin, etoposide and cisplatin (BEP) or EP chemotherapy under standardized treatment and PET evaluation criteria. Methods: Pts with advanced-stage seminoma were treated with BEP or EP according to guidelines. PET/CT examinations were performed at baseline, after two cycles in all pts and after chemotherapy at physician’s choice. PET/CT response was qualitatively evaluated by two independent nuclear medicine physicians. Contrast-enhanced CT scans were also performed according to the guidelines (at baseline, after treatment, during follow-up). The primary endpoint was the relapse-free survival (RFS). Results: From 01/2009 to 01/2017, 75 consecutive pts were enrolled, of whom 70 were evaluable. The clinical stage was IIA-B and IIC-III in 40% and 60% of the pts, respectively. Eight pts (11.4%) received consolidation radiotherapy. By local assessment, 46 PET/CT2 scans (65.7%) were reported as negative, and 46% of these pts presented with stage IIC-III. The median follow-up was 79 months. Five-year RFS of PET/CT2-positive pts was 75% (95%CI: 60-95%) compared with 97.8% (95%CI: 93.7-100%) of PET/CT2-negative pts (p = .002). This significant improvement in RFS was maintained when analyzing only pts with clinical stage IIC-III (p = 0.04) and by excluding those who received consolidation RT (p = 0.02). An increasing linear association was found between the maximum diameter of retroperitoneal lymph nodes and the rate of PET/CT2+. In univariable Cox regression analyses, PET/CT2+ (HR: 12.9, 95%CI: 1.5-106.9, p = 0.02) and elevated HCG levels (HR: 6.3, 95%CI: 1.2-32.3, p = 0.03) were significantly associated with RFS, whereas IGCCCG risk group was not (p = 0.1). PET/CT2 result was also associated with the tumor shrinkage post-BEP (p = 0.009), whereas complete response at CT did not predict the RFS (p = 0.3). Conclusions: No residual FDG-uptake after 2 cycles of conventional chemotherapy is prognostic in advanced seminoma, may outperform the utility of standard prognostic risk groups and may be more accurate to predict the RFS compared to standard response criteria. Benchmark RFS estimates for the design of the next clinical trials of chemotherapy de-escalation are offered.

SUN-499 Extragonadal Germ Cell Tumor Induced Thyrotoxicosis

Background: Extragonadal Germ Cell Tumors (EGCTs) are extremely rare, with an incidence of around 1/1,000,000 and highly variable prognosis dependent on subclassification as seminomatous or non-seminomatous. Non-seminomatous germ cell tumors can cause significant enough elevations in hCG to induce thyrotoxicosis via structural homology allowing for cross-reactivity with the TSH-receptor. Limited cases involving EGCTs inducing thyrotoxicosis have been studied. Case: A 27-year-old male presented to the emergency department with intractable abdominal and back pain. He reported night sweats, nausea, dizziness, and a 10 lb weight loss in 1 week. He was resting comfortably and only complaining of pain. He was moderately tachycardic, tachypneic and hypertensive, with a physical exam only remarkable for tenderness to palpation of the abdomen. Abdominal CT revealed mesenteric and retroperitoneal lymphadenopathy, bilateral adrenal enlargement, a mass in the head of the pancreas, as well as gallbladder and common bile duct distention. Lymph node biopsy was conducted for a suspected lymphoma; however, pathology found a poorly differentiated carcinoma. A diagnosis of a non-seminomatous EGCT was made when ultrasound of the testes was negative for masses and labs revealed elevations in hCG (74842 mIU/ml), and LDH (1421 U/L) with normal AFP (6.98 ng/mL). Further workup showed a slightly elevated T4 Free Thyroxine (1.55 ng/dl) with normal TSH (0.555 mIU/L); thus his thyrotoxicosis was secondary to the high HCG. Treatment for thyrotoxicosis was deferred with the expectation that symptoms would resolve when the tumor burden was decreased. Our patient had numerous other complications requiring management from nephrology, GI and urology teams in addition to endocrinology and hematology-oncology. Bleomycin, Etoposide and Cisplatin (BEP) combination chemotherapy was initiated after recovery from acute complications. Further pathology evaluation suggested tumor susceptibility to the biologics nivolumab and pembrolizumab. Conclusion: Patients with thyrotoxicosis secondary to metastatic non-seminomatous germ cell tumors often present with widespread metastasis and relatively few symptoms of thyrotoxicosis that resolve as the hCG levels decrease with chemotherapy without specific antithyroid medication. This case highlights the importance of considering clinically occult thyrotoxicosis in patients who have elevated hCG secondary to germ cell tumors. Early detection of germ cell tumor and recurrence is crucial for chemotherapeutic success. Thus, patients should be closely followed for thyrotoxicosis relapse which could potentially herald a carcinoma relapse and aid in early diagnosis.

SAT-218 Metastatic Non Seminomatous Germ Cell Tumor Masquerading as Bilateral Adrenal Masses

Context: Adrenal incidentalomas are commonly nonfunctional and can be diagnosed with imaging and biochemical testing. However, detection of rare causes of adrenal incidentalomas like metastatic adrenal tumors can makes its’ diagnosis very challenging due to vast majority of uncommon primary tumors. Consideration of biopsy for diagnosis and the awareness of rare primary tumors that can metastasize to adrenals is essential to prevent unnecessary adrenalectomies. Our case illustrates one such rare case where bilateral adrenal mass was the initial presentation of obscure retroperitoneal primary NSGCT (Non seminomatous germ cell tumor). Case Description: We present a case of a 34-year-old male with acute abdominal pain found to have huge bilateral adrenal masses. The left adrenal gland was markedly enlarged to 11 x 9 x 5 cm and the right adrenal gland was 6.5 x 3.4 x 7.7 cm. Multiple enlarged and centrally necrotic retroperitoneal lymph nodes (maximum 2.6 x 4.2 x 5.4 cm) along with iliac and inguinal lymphadenopathy were noted. The incidentalomas were proven to be biochemically nonfunctional and extensive imaging and further lab work up ruled out lymphoma, mycobacterial or fungal infection, infiltrative diseases. He then underwent a core biopsy of the left adrenal mass which showed predominantly necrotic tissue, acute inflammatory cells with histiocytes, and rare atypical cells without evidence of malignancy. Repeat core biopsy of left adrenal mass was unrevealing. He finally underwent a core biopsy of a large 4cm retroperitoneal lymph node which ultimately revealed NSGCT. Scrotal ultrasound showed testicular microlithiasis without any testicular mass. He had a very low testosterone level of 21 (241-827 ng/dL) and an a mildly elevated b-hCG (beta human chorionic gonadotropin) of 134 (0-1mIU/ml). A retroperitoneal primary NSGCT with metastasis to the adrenal glands was the most likely diagnosis (visceral metastasis) - Stage III (pTxN3M1S1). He was started on bleomycin, etoposide and cisplatin (BEP) chemotherapy. Conclusion: Rapidly progressing adrenal masses in young males should prompt consideration for metastatic germ cell tumors as a possible cause, even with near normal tumor markers such as alpha-fetoprotein (AFP) and beta human chorionic gonadotropin (B-HCG). Confirmation of the metastatic tumor, via histopathology, is required to avoid unnecessary adrenalectomy.