Colloid and 2 Papillary.Only a patient with a lobular carcinoma relapsed at 17 months.Rescue cryoablation was performed and after 12 months she remains without signs of recurrence.So, local control was achieved in all patients.Three patients died of causes unrelated to BC during follow up.All procedures were well tolerated with local anesthesia and there were no serious complications.Conclusion(s): Ultrasound-guided cryoablation with ET constitutes an effective combined treatment for the local control of ER+, HER2-BC in patients with clinical stage I/II and omission for surgical axillary staging.Cryoablation is a very well tolerated procedure without morbidity.

Background: Aromatase inhibitor (AI) induced arthralgia/myalgia (AIA) is a frequent side-effect of AI-therapy. We investigated the effect of a simple, home-based walking program outdoors, beginning at the start of AI-therapy, on the incidence of AIA, as well as symptom burden and quality of life (QoL) during 24 weeks.

Treatment results of AML in elderly patients are unsatisfactory. In an open label randomized phase II study, we investigated whether addition of the XPO1 inhibitor selinexor to intensive chemotherapy would improve outcome in this population. 102 AML patients > 65 years of age (median 69 (65–80)) were randomly assigned to standard chemotherapy (3 + 7) with or without oral selinexor 60 mg twice weekly (both arms n = 51), days 1–24. In the second cycle, cytarabine 1000 mg/m 2 twice daily, days 1–6 with or without selinexor was given. CR/CRi rates were significantly higher in the control arm than in the investigational arm (80% (95% C.I. 69–91%) vs. 59% (45–72%; p = 0.018), respectively). At 18 months, event-free survival was 45% for the control arm versus 26% for the investigational arm (Cox-p = 0.012) and overall survival 58% vs. 33%, respectively ( p = 0.009). AML and infectious complications accounted for an increased death rate in the investigational arm. Irrespective of treatment, MRD status after two cycles appeared to be correlated with survival. We conclude that the addition of selinexor to standard chemotherapy does negatively affect the therapeutic outcome of elderly AML patients. (Netherlands Trial Registry number NL5748 (NTR5902), www.trialregister.nl).

24 pts still on treatment (Tx). 1 pt is off from a unrelated condition. All pts escalated to V 400 mg w/o any DLTs noted. Treatment‐ emergent adverse events (TEAEs) were reported in 100% of pts, and grade 3+ TEAEs were reported in 26 (93%) patients. The most common all‐grade TEAEs (≥50% of pts), regardless of relationship to study Tx, were fatigue, neutropenia and diarrhea. Grade ≥3 TEAEs reported in ≥50% pts were neutropenia (68%) and thrombocytopenia (50%). No pts have withdrawn or d/c Tx due to AEs. There was one grade 5 event, in a non‐evaluable pt, related to a PE that occurred prior to DLT period. In the 28 evaluable pts the ORR (CR/PR) was 96% (27/28 pts) with CR/CRu of 89%. Of the responding pts, two had PD, one w/ CR and one w/ PR. All pts with PD had baseline TP53 mutation. MRD testing was successful in all pts. At time of submission 20 of 28 (71%) were MRD ‐ at 10‐6. Conclusions: Interim results show that at the MTD the combination of V 400 mg daily, L 20 mg, with R is safe with a manageable toxicity profile and a high ORR and MRD ‐ in pts with newly diagnosed MCL. Safety data is consistent with the AE profile noted for each drug without any unexpected or unique AEs. Updated results including BH3 profiling will be presented at the meeting. EA ‐ previously submitted to ASCO 2021 The research was funded by: Abbvie,Rogel Cancer Center, BMS (drug only)

Background: Prognostic factors for elderly patients ≥60 years of age with classical Hodgkin Lymphoma (cHL) are not well established. Previous studies have shown that patient-related factors such as comorbidities and performance status (ECOG-PS), disease-specific factors (extranodal disease) and markers of host inflammation (e.g. neutrophil-lymphocyte ratio [NLR]) can be associated with clinical outcomes in elderly patients with cHL. Therefore the aim of this study was to evaluate the association of cause-specific survival (CSS) and overall survival (OS) with age, stage, Charlson comorbidity index (CCI) and these additional patient- and disease-related factors in a large dataset of elderly patients with cHL. Method: Joint analysis of Princess Margaret and Swiss elderly cHL databases of patients from 2000 to 2018. Main inclusion criteria were age ≥60 years, diagnosis of cHL, treatment with chemotherapy (CT) or combined modality therapy (CMT). Patients with nodular-lymphocyte predominate HL (NLPHL) and treated with radiotherapy alone were excluded. Univariable and multivariable models were applied. Results: Overall, 309 patients from 1 Canadian (n = 72) and 15 Swiss centers (n = 237) were included. Excluded were 10 patients with RT alone and 11 with NLPHL. Median age was 70 years (range 60 – 91), median CCI was 7 (4 – 16), 17.2% of patients had stage I, 30.1 % stage II, 29.9% stage III and 28.5% stage IV cHL. Overall, 5-years OS was 62.4% [95%CI 56.8 – 68.5] and 5-years CSS was 82.6% [78.1 – 87.4]. 189 (61.2%) patients were treated with CT alone, 120 (38.8.%) patients with CMT; 240 (77.7%) patients received anthracycline-containing CT, 69 (22.3%) patients received non-anthracycline-containing CT. In univariable analysis, age, stage, CCI, NLR and ECOG-PS showed significant associations with both endpoints, all p-values < 0.01. Results of the multivariable analysis are demonstrated in table1. Conclusion: In this large, international cohort of patients aged ≥60 years with cHL age, CCI and ECOG-PS are independent factors associated with OS. Age and stage are independently associated with cause-specific survival while NLR and extranodal disease are not independently associated with clinical outcomes. *contributed equally Keywords: Diagnostic and Prognostic Biomarkers, Hodgkin lymphoma No conflicts of interest pertinent to the abstract.

In elderly patients (pts) with metastatic breast cancer (mBC), there is no generally accepted 1st line chemotherapy (CT) and only scarce data on any CT regimen. Eribulin mesylate (1.4 mg/m2) in first line mBC achieved a clinical benefit rate (CBR; CR, PR or SD ≥ 6 months (mts)), of 26 - 52%. Less than 10% of pts in the registration-trial were ≥ 70 years (y); dose reductions were frequent in the elderly. We hypothesized: a reduced dose with less toxicity will lead to longer treatment duration and comparable CBR to the standard dose. Single-arm 2-stage phase II trial investigating a reduced starting-dose of eribulin mesylate 1.1 mg/m2 d1+8 q3wk in pts ≥ 70y with CT-naïve mBC. Disease control rate at 6 mts (CBR) was the primary endpoint. A Simon's optimal single arm two-stage design to test H0 (CBR ≤ 35%) against H1 (CBR ≥ 50%) with a type-I error of 0.05 and power of 80% required 77 pts. Patient reported on neuropathy (FACT/GOG-Ntx) at the start of each cycle. From Aug 2015 to Feb 2019, 77 pts were accrued. Median (m) age was 76y (70-89); PS 0-1 in 90%, PS 2 in 10%; 64% had co-morbidities; 45% liver metastases, 3% bone-only disease. CBR was 40% (90% CI 31-50), ORR 22% (95%CI 13-33), mPFS 5.4 mts (95% CI 4.5-7.7) and mOS 16.1 mts (95% CI 13.5-26.9). The median number of cycles was 6 (1-24); dose modifications were necessary in 35% of pts; median dose per cycle was 2.1 mg/m2 (1.1-2.3). In 9 pts, >15 cycles were given. Main reasons for treatment discontinuation were progressive disease (57%), patient refusal (14%) and unacceptable toxicity (11%). Neutropenia G3 occurred in 10%, G4 in 12% of pts. Two pts (3%) suffered febrile neutropenia. Sensory neuropathy in 23% was usually mild (12% G1, 5% G2, 6% G3), median patient-reported neuropathy scores remained stable for at least 15 cycles. We report the first prospective data on treatment with 1st line Eribulin in elderly pts. A reduced starting dose of 1.1 mg/m2 is safe and the efficacy as expected, although the lower boundary of the 90% CI crossed the predefined threshold. A relevant subgroup of pts had prolonged disease control and tolerated this long time treatment without worsening of patient-reported neuropathy.

Hodgkin lymphoma (HL) in older patients appears to be a different disease compared with younger patients with historically lower survival rates. This is related to a variety of factors, including increased treatment‐related toxicity, the presence of comorbidities, and biologic differences. In order to better assess the clinical characteristics, treatment strategies, and outcome of this particular population, we conducted a population‐based, retrospective analysis including 269 patients with HL older than 60 years (median age 71 years, range 60–94), treated between 2000 and 2017 in 15 referral centers across Switzerland. Primary endpoints were overall survival (OS), progression‐free survival (PFS), and cause‐specific survival (CSS). The vast majority of patients were treated with curative intent, either with a combined modality approach (chemotherapy followed by radiation therapy) or with systemic therapy. At a median follow‐up of 6.6 years (95% confidence interval [CI], 6.0–7.6), 5‐year PFS was 52.2% (95% CI, 46.0–59.2), 5‐year OS was 62.5% (95% CI, 56.4–69.2), and 5‐year CSS was 85.1.8% (95% CI, 80.3–90.1) for the entire cohort. A significant difference in terms of CSS was observed for patients older than 71 years in comparison to patients aged 60–70 years (hazard ratio 2.6, 1.3–5.0, p = 0.005). Bleomycin‐induced lung toxicity (BLT) was documented in 26 patients (17.7%) out of the 147 patients exposed to this compound and was more frequent in patients older than 71 years (15/60, 25%). Outcome of HL pts older than 71 years appeared to decrease substantially in comparison to the younger counterpart. Treatment‐related toxicities appeared to be relevant, in particular, BLT. New, potentially less toxic strategies need to be investigated in prospective clinical trials in this particular frail population.

Objective: To investigate clinical factors associated with prolonged progression-free survival (PFS) and overall survival (OS) in relapsing epithelial ovarian cancer (EOC) patients with BRCA mutations and receiving olaparib as maintenance therapy in daily practice. Methods: Multicenter (8 hospitals) European retrospective study of relapsing EOC patients having germline or somatic mutations of BRCA1/BRCA2 genes and treated with olaparib as maintenance therapy after platinum-based chemotherapy. Results: One hundred and fifteen patients were included. Median age was 54 years. There were 90 BRCA1 carriers, 24 BRCA2 carriers and one patient had germline mutation of BRCA1 and BRCA2. Six patients had somatic mutations (all BRCA1) and 109 had germline mutations. Ninety percent had serous carcinomas and were platinum-sensitive. Following ultimate platinum-based chemotherapy, 69% of the patients had normalization of CA-125 levels and 87% had RECIST objective responses, either partial (53%) or complete (34%). After a median follow-up of 21 months, median PFS was 12.7 months and median OS was 35.4 months. In multivariate analysis, factors associated with prolonged PFS under olaparib were: platinum-free interval (PFI) >= 12 months, RECIST complete response (CR) or partial response (PR) and normalization of CA-125 upon ultimate platinum-based chemotherapy. Factors associated with prolonged OS were PFI >= 12 months, CR and normalization of CA-125. Conclusions: Platinum-free interval >= 12 months, complete response and normalized CA-125 levels after ultimate platinum-based chemotherapy are associated with prolonged PFS and OS in relapsing BRCA1/BRCA2 mutated ovarian cancer patients who received olaparib as maintenance therapy. (C) 2019 Elsevier Inc. All rights reserved.

Introduction: Approximately 20% of Hodgkin lymphoma (HL) patients (pts) are older than 60 years at diagnosis. Despite the fact that HL remains a highly curable disease, this particular group of pts tends to have a less favorable outcome than their younger counterparts. This is mainly related to the increased toxicity resulting in higher treatment-related mortality and insufficient dosing of the drugs applied. Methods: We conducted a population-based, retrospective analysis which aimed to investigate patient characteristics, treatment strategies and outcome of pts with HL older than 60 years of age, treated between 2000 and 2017, in 15 Centers across Switzerland. Results: We identified 249 pts with the following characteristics: Median age at diagnosis 71 years (range: 60-94), 123 pts 60-70 years, 89 pts 71 – 80 years, 37 pts > 80 years. 158 (63.5%) male, 191 (81.7%) Performance Status (PS) 0-1, Charlson Comorbidity Index (CCI) low (2-4 points) in 42 (16.9%) pts and high (> 4 points) in 205 (82.3%) pts. 121 (49%) pts with stage I/II ; 126 (51%) with stage III/IV and the following histologies: 238 (96%) classical HL, 11 (4%) nodular lymphocyte predominant HL. Treatment was performed as follows: radiotherapy (RT) only in 11 (4%) pts; chemotherapy followed by RT in 79 (32%) pts, chemotherapy only 142 (57%) pts; 221 pts received systemic therapy with: ABVD 117 (53 %); BEACOPPesc. 8 (4.0 %), other chemotherapy combinations or single agent 57 (25 %), antibody drug conjugate one pt; 12 (5.0 %) pts received best supportive care, in 5 (2%) pts information was missing. Haematological toxicity ≥G2 was observed in 111 (42.7%) pts, 65 (25%) pts presented with infections and 44 (17%) pts with febrile neutropenia. Bleomycin lung-toxicity (BLT) was documented in 25 (18%) pts: 6 (4 %) pts had mild toxicity (radiologic changes only), 12 (9%) pts had severe toxicity (leading to hospitalization), in 7 (5%) pts severity was unknown. In 58 (24%) pts treatment was discontinued prematurely due to toxicity. 171 (68.7%) pts achieved complete remission, 30 (12%) partial response. 58 (23%) pts relapsed/progressed after first line treatment. 25 (23%) pts died of HL and 15 (14%) of treatment toxicity. With a median follow-up of 4.1 years (range: 0.05 - 17.95) for the whole study population, progression-free survival (PFS) at 2 and 5 years was 81% and 72% respectively, cause-specific survival (CSS) at 2 and 5 years was 85% and 78%, respectively. CSS for pts 71-80 years vs 60-70 years; HR = 3.25, p<0.001 and > 80 years vs 60-70 years; HR 3.84, p = 0.001. Keywords: elderly; Hodgkin lymphoma (HL). Disclosures: Moccia, A: Other Remuneration: Advisory Roche, Janssen, Takeda.

58.5% der Frauen zwischen 20 und 39 Jahren sind übergewichtig, adipös oder peradipös. Die Inzidenz steigt weltweit und damit das Risiko für internistische Folgeekrankungen, Sterilität und Komplikationen in der Schwangerschaft (SS). Dauerhaft veränderte Verdauungsabläufe nach Bariatrie haben u.U. erhebliche Langzeitwirkungen (Malabsorption, Störung von Wasser- und Mineralhaushalt, Diarrhoe, Gallen- oder Nierensteine, Ulcera, gastroösophagealer Reflux, Anastomosenstenosen, innere Hernien, etc.).

Background: DN has shown superiority in delaying skeletal related events when given q4w over zoledronic (ZA) acid given q4w. Newer data have shown that ZA given q12w is non-inferior to ZA q4w. The primary endpoint of REDUSE is to show non-inferiority for DN q12w versus q4w (SSE). Here we present the data for the secondary endpoint hypocalcemia (HC). Methods: Patients with metastatic breast cancer (BC) or metastatic castration resistant prostate cancer (PC) (planned N = 1380) were randomized 1:1 to receive DN q4w (Arm A) versus q12w (Arm B) after a 3-month induction phase with application q4w. All patients received vitamin D 400 U (ViD) and calcium (Ca) 500 mg daily. Measurement of serum-calcium was mandatory before each DN injection. This safety interim analysis was performed after 3.5 years of accrual. (N = 634; BC N = 351, PC N = 283). Results: Patients who received at least 1 dose of DN were considered evaluable. HC was the most common side effect with 23.7% overall (BC 18.6%, PC 30.2%). While HC occurred in 31.6% in Arm A, the rate was 15.8% in Arm B. Grade 3/4 HC was rare (overall: 1.3%, all with PC). After 1 year of treatment, the incidence of HC was lower in both arms (A: 27.2%, B: 14.3%). Since HC improved in more patients in Arm B than Arm A whereas it got worse in Arm A compared to Arm B, a remarkable difference for HC was noticed between the two arms (Table).Table: 1703PChange in HC grade after week 16 in patients with HC during induction treatment (196/634) (week 1 – 12: DN q4w Arm A+B, thereafter q4w Arm A, q12w Arm B)Arm A (N = 106)Arm B (N = 90)n (%)n (%)Worsening48 (45.3%)23 (25.6%)Stable29 (27.4%)15 (16.7%)Improving29 (27.4%)52 (57.8%)Arm A: Denosumab q4w, Arm B: Denosumab q12w. Open table in a new tab Arm A: Denosumab q4w, Arm B: Denosumab q12w. Conclusions: In our trial up to 30% of all patients treated with DN experienced HC in the q4w induction phase despite mandatory supplementation and measurement of ViD and Ca. This rate was considerably higher than reported in the registration trials of DN (PC 13.0%, BC 5.5%). After randomization the appearance of HC is remarkably lower in the q12w arm compared to q4w. This suggests that DN given q12w has a more favorable long time toxicity profile (HC) compared to DN q4w. Clinical trial identification: NCT02051218. Legal entity responsible for the study: Swiss Group for Clinical Cancer Research (SAKK). Funding: Swiss State Secretariat for Education, Research and Innovation (SERI) and Santésuisse. Disclosure: R. von Moos: Advisory board: Amgen, Novartis, Roche. S. Gillessen: Compensated consultancy and advisory roles (including IDMC): AAA International, Active Biotech, Astellas Pharma, Bayer, Bristol-Myers Squibb, CellSearch (Menarini Silicon Biosystems), Clovis, Curevac, Dendreon, Ferring, Innocrin, Janssen, MaxiVAX SA, Millennium, Novartis, Orion, Pfizer, Roche, Sanofi Aventis; Speakers Bureaus (compensated): Janssen, Novartis; Patent application for a biomarker method (WO 2009138392 A1). All other authors have declared no conflicts of interest.

Background: High rates of venous thromboembolic events (VTE) are reported for patients (pts) with upper GI-cancers (stomach, pancreas) and treatment with Cisplatin (Cis), but mainly in retrospective analyses and in advanced disease. A prospective analysis of VTE in pts with resectable esophageal cancer is warranted. Methods: Pre-planned analysis of VTE in a multicenter phase III trial according to reported AEs and SAEs from start of preoperative treatment until 6 months postoperatively. Pts with resectable esophageal cancer (T2N1-3; T3-4aNx) received 2 cycles of induction chemotherapy (CT) with Docetaxel (Doc) 75mg/m2, Cis 75 mg/m2 followed by chemoradiation (CRT) with 45 Gy, Doc 20 mg/m2 and Cis 25 mg/m2 weekly and then surgery or were randomly assigned to the same treatment with addition of neoadjuvant and adjuvant cetuximab. Results: Of 300 pts 29 VTE were reported in 26 pts with an incidence rate (IR) of 8.7%. 3 pts had 2 VTE. 72% (21/29) of all VTE occurred preoperatively. No significant difference between treatment arms was found, odds ratio (OR) 0.8 [95%CI 0.4-1.9], p = 0.7. Grades (G) of VTE according to CTCAE v4.0: 3% (1/29) G1, 41% (12/29) G2, 45% (13/29) G3 and 10% (3/29) G5. In a multivariable logistic regression including baseline hemoglobin, platelets, neutrophils, BMI, treatment arm and histology, only adenocarcinoma (IR 11.1%, 21/189) compared to squamous cell cancer (IR 4.5%, 5/111) was significantly associated with VTE-risk during treatment, OR 2.9 [95%CI 1.02;8.4], p = 0.046. Baseline Khorana risk score (KRS) for VTE was 0 in 73% (19/26), 1-2 in 23% (6/26) of pts and 3 in one patient with VTE (≥ 3 equal to high-risk and recommendation for prophylaxis). Median PFS in pts with VTE was 2.1 yrs vs. 2.5 yrs for pts without VTE. Conclusions: This first prospective analysis of VTE in resectable esophageal cancer pts reveals a high IR during perioperative therapy of almost 9% comparable to high-risk pts according to KRS. Only one of these pts would have been identified by KRS as high-risk. Prophylactic anticoagulation balanced against individual bleeding risks could be considered in esophageal cancer pts treated with neoadjuvant Cis-based CT and RCT, especially in adenocarcinoma. Clinical trial identification: NCT 01107639 (release date: April 20, 2010) Legal entity responsible for the study: Swiss Group for clinical Cancer research (SAKK) Funding: Merck KGaA, Darmstadt, Germany Disclosure: P. Thuss-Patience: Advisory boards: Roche, BMS, Nordic, MSD, Pfizer, Lilly. Research funding: Novartis. M. Bitzer: Consulting/advisory boards: Bayer Healthcare, BMS. W. Eisterer: Advisory boards: Roche, Merck, Amgen, Lilly, Celgene. M. Stahl: Advisory board: MSD, Amgen, Sanofi, Servier. T. Ruhstaller: Advisory boards: Novartis, Roche, Astra-Zeneca. All other authors have declared no conflicts of interest.

Introduction: Mantle-cell lymphoma (MCL) remains incurable with frequent relapses, limited treatment options and progressively shorter disease-free survival with every relapse. The Bruton's tyrosine kinase inhibitor ibrutinib (IBRU) and the proteasome inhibitor bortezomib (BOR) have both single agent activity and regulatory approval in MCL. IBRU and BOR both result in a downregulation of NF-κB activity via different molecular targets. IBRU resistance involves mutations in genes of the NF-κB pathway. The combination of both drugs provides synergistic cytotoxicity in BOR-sensitive and refractory MCL in vitro. Methods: We included patients (pts.) with confirmed MCL, refractory or relapsed after ≤2 lines of a non-BOR-containing chemotherapy (incl. high-dose chemotherapy), and excluded pts. with prior BOR/IBRU therapy, with CNS disease, in need of anticoagulation (warfarin, vitamin K antagonists), and with active Hepatitis B, C or HIV infection. Pts. received 6 21-days cycles of IBRU + BOR, followed by IBRU maintenance until disease progression or unacceptable toxicity. To establish the recommended phase II dose, a 3 + 3 dose escalation design was used. BOR was given s.c. at the labelled dose (1.3 mg/m2, days 1, 4, 8, 11 q3w), and IBRU continuously at 420 mg/day (level 1), and 560 mg/day (level 2). Dose-limiting toxicities (DLTs) were assessed in cycle 1 and were defined as study drug-related adverse events (AE, CTCAE, v4.0) including ≥7 missed days of IBRU, ≥2 missed doses of BOR, delay of >2 weeks of cycle 2, hematological DLTs (ANC < 0.5 for ≥7 consecutive days, febrile neutropenia, and G4 thrombocytopenia), and non-hematological DLTs ≥ G3. The antitumor activity of the combination was a secondary objective. Results: No patient experienced a DLT during the first cycle, the minimum of 9 pts. was needed. The most frequent AEs of the combination treatment included thrombocytopenia (8 pts), peripheral polyneuropathy (PNP) and fatigue (6 pts. each), anemia and diarrhea (5 pts. each). The majority of the AEs were G1 & 2. Six pts. experienced G3 AEs with thrombocytopenia (3 pts.), PNP, lung infections, lymphocyte count decreased (2 pts.), and one pt had a G4 thrombocytopenia. Although considered G1, an unexpected AE in 5 pts. was an injection site reaction. In a protocol amendment, 8 mg dexamethasone will now be allowed as co-medication prior to injecting BOR. At data cut-off (January 31, 2017), 2 pts. had stopped therapy because of progressive disease (one at end of cycle 3, one during maintenance). 3 pts. are in follow-up incl. 1 pt who went on to successful stem-cell transplantation. Conclusions: IBRU with twice-weekly BOR at 1.3 mg/m2 s.c. can safely be administered. We define IBRU 560 mg/day as the recommended phase II dose for the combination with standard dose BOR. The safety and clinical efficacy of dose is currently being tested in the ongoing phase II part of this trial. (ClinicalTrials.gov Identifier: NCT02356458). Keywords: bortezomib; ibrutinib; mantle cell lymphoma (MCL)

Background: Official guideline “indications and methods of hysterectomy” to assign indications for the different methods published and coordinated by the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (OEGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). Besides vaginal and abdominal hysterectomy, three additional techniques have been implemented due to the introduction of laparoscopy. Organ-sparing alternatives were also integrated. Methods: The guideline group consisted of 26 experts from Germany, Austria and Switzerland. Recommendations were developed using a structured consensus process and independent moderation. A systematic literature search and quality appraisal of benefits and harms of the therapeutic alternatives for symptomatic fibroids, dysfunctional bleeding and adenomyosis was done through MEDLINE up to 6/2014 focusing on systematic reviews and meta-analysis. Results: All types of hysterectomy led in studies to high rates of patient satisfaction. If possible, vaginal instead of abdominal hysterectomy should preferably be done. If a vaginal hysterectomy is not feasible, the possibility of a laparoscopic hysterectomy should be considered. An abdominal hysterectomy should only be done with a special indication. Organ-sparing interventions also led to high patient satisfaction rates, but contain the risk of symptom recurrence. Conclusion: As an aim, patients should be enabled to choose that therapeutic intervention for their benign disease of the uterus that convenes best to them and their personal life situation.

Single-dose Carboplatin (C) AUC7 is an adjuvant treatment option in Seminoma stage I. Many of these patients have very good renal function and hence high absolute doses of C are frequently administered. Some experts and clinical guidelines recommend capping of C dose at Creatinine-Clearance (Crea-Cl) of 125 ml/min because of concerns of excessive toxicity. The rationale for these concerns has not been explored in patients with Seminoma stage I so far. Analysis of a cohort of patients with stage I Seminoma treated with C AUC 7 in 2 Swiss centres 2005 – 2015. Main inclusion criteria: Normal blood count at treatment, minimum of 2 measurements during first 8 weeks of follow-up. Comparison of incidence and grade (CTCAE v4.0) of hematological adverse events (AEs) in patients with Crea-Cl < vs. > 125 ml/min without dose capping. 74 patients with 229 documented measurements were identified. Median age 41 years (Range 22 – 71), Crea-Cl (Cockroft-Gault) 126 ml/min (70 - 206), C dose 1013 mg (700 - 1477). 12 patients with Crea-Cl >125 ml/min and capped C dose (resulting in AUC <7) were excluded. In 35 patients with Crea-Cl <125 ml/min a total of 74 AEs were documented, 81% were grade 1; compared to 61 AEs, 82% of them grade 1 (P= . 89) in 27 patients with Crea-Cl >125 ml/min and no dose capping. No statistically significant differences of AEs in patients with Crea-Cl > vs. < 125 ml/min were noted. In each group one clinical relevant AE with subsequent interventions occurred: Febrile neutropenia in 1 patient with with Crea-Cl <125 ml/min, 1 patient with Crea-Cl >125 ml/min received one platelet transfusion (2.8% vs. 3.7%, P= .85). For further details see table.Tabled 1Crea-Cl <125 ml/min (N = 35)Crea-Cl >125 ml/min & no dose capping (N = 27)PDecreased Haemoglobin71% (25)56% (15).28Decreased Platelet Count57% (20)78% (21).11Decreased Platelet Count >G211% (4)29% (6).31Decreased White Cell Count37% (13)48% (13).44Decreased Neutrophil Count46% (16)44% (12).92Decreased Neutrophil Count >G220% (7)19% (5).88AEs with clinical interventions2.8% (1 hospitalisation with febrile neutropenia G3)3.7% (1 platelet transfusion in thrombocytopenia G4).85 Open table in a new tab Concerns of excessive toxicity in patients with Seminoma stage I and Crea-Cl >125 ml/min treated with adjuvant C AUC7 are not supported by our data. Most AEs were grade 1 (>80%). There was also no statistically significant excess of AEs > grade 2. Therefore capping of C dose is not justified in this Situation.

BACKGROUND Following inguinal orchidectomy, management options for patients with stage I seminoma include initial surveillance or treatment with adjuvant radiotherapy or chemotherapy. The anticipated relapse rate for patients followed by surveillance alone is ∼15%, with adjuvant treatment this risk is reduced to ∼4%-5% at 5 years. After carboplatin treatment, follow-up strategies vary and there are no validated, predictive markers of relapse. PATIENTS AND METHODS We conducted a retrospective analysis of all patients presenting with stage I seminoma who received a single cycle of adjuvant carboplatin in South Central England between 1996 and 2013. We report on outcome and the results of univariate and multivariate analysis evaluating possible risk factors for post carboplatin relapse. RESULTS A total of 517 eligible patients were identified. All underwent nuclear medicine estimation of glomerular filtration rate before treatment with carboplatin (dosed at area under the curve × 7). With a median follow-up of 47.2 months (range 0.4-214 months), 21/517 patients have relapsed resulting in a 5-year estimated relapse-free survival of 95.0% (95% confidence interval 92.8% to 97.3%). Median time to relapse was 22.7 months (range 12.5-109.5 months). Relapse beyond 3 years was rare (4/517; 0.8%). Twenty of 21 (95%) relapsed patients had retroperitoneal lymph node metastases. The majority (16/21; 76%) of patients had elevated tumour markers at relapse. Twenty of 517 (3.9%) patients developed a new contralateral testicular germ-cell cancer. There were no seminoma-related deaths. Tumour size was the only variable significantly associated with an increased risk of relapse. CONCLUSIONS Overall results for this large cohort of patients confirm an excellent prognosis for these patients with outcomes equivalent to those seen in prospective clinical trials. Increasing tumour size alone appears to be associated with an increased risk of post chemotherapy relapse.

ABSTRACT Aim: The prognosis for stage 1 seminoma is excellent with a cure rate approaching 100%, but without adjuvant therapy, approximately 15-20% of patients may relapse and require salvage treatment. The TE19 trial confirmed the efficacy of a single dose of adjuvant carboplatin (AUC 7) in reducing recurrence rate. This study reviews our regional experience, with a focus on the presentation, management and outcome of relapsed patients. Methods: A retrospective clinical database was constructed for patients who have received one cycle of adjuvant carboplatin (AUC 7) between 1996 and 2013 for stage 1 seminoma. Tumour characteristics, clinical outcomes and patient relapse were evaluated. Results: 518 patients were eligible for inclusion. All patients underwent nuclear medicine measurement of GFR. Median age of diagnosis was 38 (range 18 – 73). Median tumour size was 32mm (range 4 – 110) and 57% had rete testis invasion. Median time from orchidectomy to chemotherapy was 44.5 days (range 10 – 174). 18 patients (3.5%) presented with bilateral disease or developed a contralateral germ cell tumour during follow up; median 94 months (range 0 – 265). With a median follow up of 43.2 months (range 0 – 199), 22 patients (4.2%) have relapsed. Median time to relapse was 22.4 months (range 11 – 108) with the majority of patients (13/518; 2.5%) relapsing within 2 years. Relapse beyond 4 years was very uncommon (4/518: Conclusions: This is, to our knowledge, the biggest non-trial series describing the clinical outcome and relapse data of patients with stage 1 seminoma treated with a single cycle of adjuvant carboplatin chemotherapy. Our results confirm the excellent prognosis for these patients with outcomes similar to those of prospective clinical trials. Disclosure: All authors have declared no conflicts of interest.

Aim: The prognosis for stage 1 seminoma is excellent with a cure rate approaching 100%, but without adjuvant therapy, approximately 15-20% of patients may relapse and require salvage treatment. The TE19 trial confirmed the efficacy of a single dose of adjuvant carboplatin (AUC 7) in reducing recurrence rate. This study reviews our regional experience, with a focus on the presentation, management and outcome of relapsed patients.