Andrew Gogbashian's research while affiliated with The Hillingdon Hospitals NHS Foundation Trust and other places

Introduction/Background Malignant ovarian germ cell tumours (MOGCTs) are rare and aggressive malignancies mainly affecting young women. Unlike testicular GCTs, prognostic factors are poorly understood, but small series have most consistently suggested that advanced stage best predicts worse outcomes. Here, we examine a large, international patient series to identify new adverse prognostic factors. Methodology We evaluated 254 patients treated in Charing Cross Hospital and Mount Vernon Cancer Centre, UK and in Multi-centre Italian Trials in Ovarian Cancer (MITO) group between 1971 and 2018. Descriptive statistical, survival and Cox regression techniques were performed using STATA (StataCorp, v.16, Texas, USA). Results Median age was 26 years (IQR, 20–32). There were 22.4% dysgerminomas, 18.5% immature teratomas, 33.5% yolk sac, 17.7% mixed, 1.2% embryonal, 2.4% choriocarcinoma and 4.3% unclassified. FIGO stage distribution was 31.5% (IC/M), 12.6% (II), 40.5% (III) and 15.4% (IV). First line chemotherapy consisted of BEP, POMB/ACE or other regimens for 48.0%, 42.5% and 9.5% of patients, respectively. Recurrences received high dose chemotherapy (HDCT), conventional chemotherapy ± surgery, and surgery alone in 24.4%, 65.9% and 7.3% of cases.At multivariable analysis, age ≥35 at presentation [HR 2.3, 95%CI (1.0–5.0), p=0.04], stage [HR 1.5, 95%CI (1.0–2.1), p=0.032], and non-dysgerminoma versus dysgerminoma [HR 12.7, 95%CI (1.7–94.0), p=0.013] were significantly associated with worse cancer-specific survival (CSS). Twenty-year CSS for stage IC/M, II, III, and IV were 94.8%, 82.3%, 83.2% and 84.3%, respectively. In patients relapsing or failing to achieve a complete response, HDCT showed a trend for improved 5-year CSS compared to conventional treatments [HR 0.5, 95%CI (0.2–1.5), p=0.241]. Conclusion This study demonstrated that in addition to advanced stage, age ≥35 years, and non-dysgerminoma, but not immature teratomas, are independent adverse prognostic factors for CSS. Strikingly, stage IV disease can still achieve >80% long-term survival rates. HDCT may improve outcomes for relapsing/incomplete responding patients.

Background In patients with cancer, the current gold standard for assessing response to treatment involves measuring cancer lesions on computed tomography (CT) imaging. The percentage change in size of specific lesions determines whether patients have had a complete/partial response or progressive disease, according to RECIST criteria. Dual Energy CT (DECT) permits additional measurements of iodine concentration, a surrogate marker of vascularity. Here we explore the role of changes in iodine concentration within cancer tissue on CT scans to assess its suitability for determining treatment response in patients with high grade serous ovarian cancer (HGSOC). Methods Suitable RECIST measurable lesions were identified from the CT images of HGSOC patients, taken at 2 different time points (pre and post treatment). Changes in size and iodine concentration were measured for each lesion. PR/SD were classified as responders, PD was classified as non-responder. Radiological responses were correlated with clinical and CA125 outcomes. Results 62 patients had appropriate imaging for assessment. 22 were excluded as they only had one DECT scan. 32/40 patients assessed (113 lesions) had received treatment for relapsed HGSOC. RECIST and GCIG (Gynaecologic Cancer Inter Group) CA125 criteria / clinical assessment of response for patients was correlated with changes in iodine concentration, before and after treatment. The prediction of median progression free survival was significantly better associated with changes in iodine concentration (p = 0.0001) and GCIG Ca125 / clinical assessment (p = 0.0028) in comparison to RECIST criteria (p = 0.43). Conclusion Changes in iodine concentration from dual energy CT imaging may be more suitable than RECIST in assessing response to treatment in patients with HGSOC. Trial Registration CICATRIx IRAS number 198179, 14 Dec 2015, https://www.myresearchproject.org.uk/ .

419 Background: Patients presenting with intermediate and poor risk germ cell tumours tend to be young and fit. Although more than half of patients may hope to be cured, a proportion will die because of their cancer. An aggressive strategy is required to maximise the chance of cure. Alternating high dose chemotherapy regimens have been trialled with varying outcomes. We present real world data demonstrating the efficacy and safety of first-line POMB/ACE (Cisplatin, Vincristine, Methotrexate, Bleomycin alternating with Actinomycin D, Cyclophosphamide, Etoposide) for these patients. Methods: 40 metastatic germ cell patients treated with POMB/ACE were identified at our centre. Patients were classified as being in intermediate or poor prognostic groups based on the International germ cell cancer collaborative group classification (IGCCCG). Treatment was administered every 2 weeks for up to 7 cycles. Response to treatment was determined by radiological imaging and serum tumour markers. Toxicities were evaluated using CTCAE version 5.0. Results: Clinical characteristics were as follows: median age at diagnosis 32 years (range 18-69). 36 patients (90%) were male and 4 patients (10%) were female. 29 (73%) presented with poor risk disease and 11 (27%) with intermediate risk. Patients completed between 1 and 7 cycles of POMB/ACE with the median number of cycles being 5. Data on toxicity severity was collected where available. This is summarised in the table. One grade 4 event was noted. 10 patients experienced grade 3 toxicities. Interestingly no patients were reported to develop bleomycin lung toxicity. This may be due to bleomycin being omitted in patients felt to be at higher risk of lung toxicity (smokers, older patients, pre-existing lung conditions). 30 (75%) patients were progression free following POMB/ACE. 9 (22%) patients went on to have subsequent systemic chemotherapy regimens and high dose stem cell transplant (HDSCT), as they had high volume disease, and persistent marker positive disease. 16 (40%) patients went on to have further surgical interventions, most commonly retroperitoneal lymph node dissection (RPLND), no active malignancy was seen in the resected specimen. At a median follow-up of 43 months, 39 (97.5%) of patients are still alive. Conclusions: POMB/ACE is a safe and effective regimen for patients presenting with intermediate to poor risk germ cell tumours. Patients with high volume disease should be considered for subsequent HDSCT to achieve better outcomes. [Table: see text]

Background/aim: Treatment for advanced renal cell carcinoma (aRCC) comprises single agent or combinations of immune checkpoint inhibitors and/or anti-angiogenic agents. Pazopanib is a multitargeted anti-angiogenic tyrosine kinase inhibitor (TKI) approved as treatment for aRCC. We noted that a number of patients receiving pazopanib developed a radiological finding of small bowel lipomatosis. To evaluate the incidence of small bowel lipomatosis in patients with aRCC on treatment with pazopanib in comparison with other tyrosine kinase inhibitors. Patients and methods: We identified 12 out of 208 patients receiving pazopanib to have small bowel lipomatosis and compared their clinic-radiological findings with 314 patients with aRCC receiving other TKIs (sunitinib, cabozantinib, axitinib, and tivozanib). No patients receiving these TKIs developed small bowel lipomatosis. Results: We compared the radiological findings in patients receiving pazopanib for aRCC. The presence of lipomatosis should not be considered as a clinically relevant finding in these patients. The presence of lipomatosis has no relation with the response to treatment to pazopanib and this is a unique finding seen only in patients on pazopanib. Conclusion: Small bowel lipomatosis is an occasional finding in patients with advanced renal cancer on pazopanib and is not seen with other TKIs.

Background/aim: The occurrence of germ cell tumour (GCT) in the elderly is rare, with scarce data available. The aim of this study was to understand the clinical outcomes of patients with GCT in patients aged > 45 years. Materials and methods: A retrospective study was conducted in a large tertiary cancer centre in north-west London. Between 1 January 2003 and 31 March 2022, 108 cases of GCT in men aged > 45 years were identified and treated at the Mount Vernon Cancer Centre. The median age at diagnosis was 54 years (range = 45-70 years). Results: The 5-year survival rate of all patients was 96%, and the toxicity profile was similar to the younger age group. Conclusion: Older patients with GCT are able to tolerate chemotherapy; however, care must be taken to prevent life-threatening complications using appropriate dose modification.

A man in his mid-70s presented with a lump in his left testicle. He had previously been treated for prostate cancer with radical radiotherapy. He was on treatment for hypertension and type 2 diabetes. An ultrasound of the testes demonstrated a solid intratesticular mass for which he underwent left orchidectomy. Histology from the orchidectomy was moderately differentiated squamous cell carcinoma (SCC), positive for cytokeratin (CK) 5/6 and p63. A positron emission tomogram (PET) scan was clear of any metastatic disease. His surveillance CT, done at 12 months, revealed mediastinal, abdominal and hilar adenopathy. Biopsy of hilar lymph nodes showed SCC and this was treated with platinum-based chemotherapy. Unfortunately, the patient died after 18 months. To our knowledge, this is the first reported case of metastatic SCC of testes with extensive spread and with platinum-refractory disease.

Background: Secondary neoplasms of the bladder account for 4.5% of all bladder neoplasms however there is limited literature reporting management and survival. This is the largest single centre series presented in current literature with long term oncological follow up. Methods: This is a single institutional, retrospective cohort study of patients with a histological diagnosis of a secondary bladder neoplasm from January 2007 to December 2017 (n=40). Prognostic variables examined included age at diagnosis, histology, disease free survival and treatment. Kaplan-Meier analysis was used to calculate survival. We used multiple regression analysis to identify the most significant treatments for each population group in terms of their survival. Results: Twenty-one patients were male (53%) with a median age of 68 and 19 were female (47%) with a median age of 64. The most common secondary neoplasms and their median survival were prostate [12 patients (30%), 446 days], colorectal [9 patients (23%), 403 days], ovarian [5 patients (13%), 369 days], cervical [4 patients (10%), 148 days], breast [3 patients (8%), 241 days], lymphoma [3 patients (8%), 145 days], gastric [2 patients (5%), 66 days], and renal [2 patients (5%), 854 days]. Those receiving treatment following a secondary diagnosis demonstrated statistical significance in survival for colorectal (surgery P=0.013), prostate (radiotherapy P=0.0012 and hormonal therapy P=0.004) and ovarian cancer (chemotherapy P=0.00002). Conclusions: Prognosis and treatment depends upon the primary neoplasm. There is some survival benefit in well selected patients receiving treatment following a diagnosis of a bladder secondary.

Background CT and bone scintigraphy have limitations in evaluating systemic anticancer therapy (SACT) response in bone metastases from metastatic breast cancer (MBC). Purpose To evaluate whether whole-body MRI enables identification of progressive disease (PD) earlier than CT and bone scintigraphy in bone-only MBC. Materials and Methods This prospective study evaluated participants with bone-only MBC between May 2016 and January 2019 (ClinicalTrials.gov identifier: NCT03266744). Participants were enrolled at initiation of first or subsequent SACT based on standard CT and bone scintigraphy imaging. Baseline whole-body MRI was performed within 2 weeks of entry; those with extraosseous disease were excluded. CT and whole-body MRI were performed every 12 weeks until definitive PD was evident with one or both modalities. In case of PD, bone scintigraphy was used to assess for bone disease progression. Radiologists independently interpreted images from CT, whole-body MRI, or bone scintigraphy and were blinded to results with the other modalities. Systematic differences in performance between modalities were analyzed by using the McNemar test. Results Forty-five participants (mean age, 60 years ± 13 [standard deviation]; all women) were evaluated. Median time on study was 36 weeks (range, 1-120 weeks). Two participants were excluded because of unequivocal evidence of liver metastases at baseline whole-body MRI, two participants were excluded because they had clinical progression before imaging showed PD, and one participant was lost to follow-up. Of the 33 participants with PD at imaging, 67% (22 participants) had PD evident at whole-body MRI only and 33% (11 participants) had PD at CT and whole-body MRI concurrently; none had PD at CT only (P < .001, McNemar test). There was only slight agreement between whole-body MRI and CT (Cohen κ, 0.15). PD at bone scintigraphy was reported in 50% of participants (13 of 26) with bone progression at CT and/or whole-body MRI (P < .001, McNemar test). Conclusion Whole-body MRI enabled identification of progressive disease before CT in most participants with bone-only metastatic breast cancer. Progressive disease at bone scintigraphy was evident in only half of participants with bone progression at whole-body MRI. © RSNA, 2020 Online supplemental material is available for this article.

Background/aim: High-dose chemotherapy (HDCT) and stem cell transplantation (SCT) have been established as the standard of care in patients with relapsed germ cell tumours (GCTs). We evaluated the safety, efficacy and tolerability of HDCT/ SCT in patients with relapsed GCTs. Patients and methods: Twenty-eight patients with relapsed GCTs, treated with HDCT, were included in this study. The conditioning regime was carboplatin, etoposide, cyclophosphamide and paclitaxel. Clinical, radiological imaging and tumour markers determined treatment outcomes. Results: Median age was 35 years (range=21-57 years) with 26 males and 2 females. Median time to first relapse was 6 months. Median time to progression after 2nd line chemotherapy was 17.3 months. Fourteen patients hadMedian survival was 62 months and 16 patients (57%) are in clinical follow-up with surveillance. Conclusion: In relapsed GCT patients, median survival may exceed 5 years post-HDCT and SCT.