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Background Available systemic 2nd or 3rd line options for MPM show a median progression-free survival (mPFS) of less than 2 months (mo) and median overall-survival (mOS) of 6-9 mo. Lurbinectedin (PharmaMar) is a novel compound with a dual role of binding to the DNA minor groove and inhibiting cytokine transcription of tumor-associated macrophages. Single MPM pts treated with lurbinectedin in early clinical trials showed encouraging outcome. The aim of current trial was to provide further data on safety and efficacy of lurbinectedin in progressive MPM. Methods MPM pts (all histologies) not amenable for local treatment and progressing after first-line platinum-pemetrexed chemotherapy +/- immunotherapy (IO) received 2nd or respectively 3rd line lurbinectedin. Lurbinectedin 3.2 mg/m2 every 3 weeks was given i.v. until progression or unacceptable toxicity. Primary endpoint was PFS at 12 weeks (PFS12wks) and would be met if achieved by at least 21 pts (p0 ≤ 35%; mPFS 2 mo). Secondary endpoints were mPFS, mOS and adverse events (AEs). Results 6 Swiss and 3 Italian centers recruited 42 pts (33 epithelioid, 4 biphasic, 5 sarcomatoid). 10/42 (23.8%) pts also received prior IO. At cut-off date (31st January 2019) PFS12wks was met by 22/42 pts (52.4%; 95%CI [38.7%; 63.5%]; p = 0.015) for mPFS of 4.1mo (95% CI [2.6; 5.5]) and mOS of 11.9mo (95% CI [9.2; 14.7]). 1 pt had complete, 1 pt partial response and 20 pts stable disease as best response. No significant difference in PFS12wks, mPFS and mOS was observed in epithelioid vs non-epithelioid MPM and prior-IO vs non-prior IO pts. All pts experienced AEs. Grade 3-4 toxicity was seen in 33 pts with most common being leuco-/lymphopenia (60.6%) and fatigue (24.2%). Febrile neutropenia was 9.1%. No pt discontinued treatment due to toxicity. Conclusions The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity compared to historical data. Neither histology nor prior IO seems to affect efficacy of lurbinectedin, but respective pts numbers are small for definitive conclusions. Further evaluation of lurbinectedin in a large randomized trial is warranted. Clinical trial identification NCT03213301. Legal entity responsible for the study Swiss Group for Clinical Cancer Research. Funding PharmaMar; State Secretariat for Education, Research and Innovation (SERI). Disclosure Y. Metaxas: Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Pierre Fabre; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Merck; Travel / Accommodation / Expenses: PharmaMar; Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Bristol Meyer Squibb; Honoraria (institution), Advisory / Consultancy: MSD; Research grant / Funding (institution): Krebsliga Graubunden; Research grant / Funding (institution): Suva Switzerland. M. Frueh: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution), Advisory / Consultancy: Takeda. F. Grosso: Travel / Accommodation / Expenses: Novocure; Travel / Accommodation / Expenses: PharmaMar; Travel / Accommodation / Expenses: Boehringer Ingelheim; Travel / Accommodation / Expenses: Novartis; Travel / Accommodation / Expenses: Bristol-Meyer Squibb; Travel / Accommodation / Expenses: Amianto-Italia-Canada-Asbestos Committee; Honoraria (self): Merck; Honoraria (self): Italian Centro per la Prevenzione e Controllo delle Malattie; Research grant / Funding (self): Associazione Famigliari e Vittime Amianto. P.A. Zucali: Honoraria (self), Advisory / Consultancy: Sanofi; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Novartis; Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self): Pfizer; Honoraria (self): Ipsen; Honoraria (self): Tesaro. G.L. Ceresoli: Honoraria (self), Advisory / Consultancy: Boehringer-Ingelheim; Advisory / Consultancy: Merck Sharp and Dohme; Honoraria (self): Astellas; Honoraria (self): Pfizer; Travel / Accommodation / Expenses: Novocure. M.T. Mark: Honoraria (institution), Advisory / Consultancy: BMS; Honoraria (institution), Advisory / Consultancy: MSD; Honoraria (institution), Advisory / Consultancy: Boehringer; Honoraria (institution), Advisory / Consultancy: AstraZeneca; Honoraria (institution), Advisory / Consultancy: Takeda. M.R.A. Perrino: Honoraria (self): Astellas; Honoraria (self): Bristol Meyer Squibb; Honoraria (self): Novartis. S. Schmidt: Advisory / Consultancy, Travel / Accommodation / Expenses: Boehringer Ingelheim; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Research grant / Funding (institution): BMS; Research grant / Funding (institution): AstraZeneca; Travel / Accommodation / Expenses: Takeda. R. von Moos: Honoraria (institution), Advisory / Consultancy: Amgen; Advisory / Consultancy: Bayer; Advisory / Consultancy: Elly Lilly; Advisory / Consultancy: Novartis; Honoraria (institution), Advisory / Consultancy: Roche; Advisory / Consultancy: Sanofi Aventis; Advisory / Consultancy: Merck-Serono; Advisory / Consultancy, Travel / Accommodation / Expenses: Tesaro; Advisory / Consultancy: Bristol-Meyers ; Advisory / Consultancy: MSD; Travel / Accommodation / Expenses: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: Vifor. All other authors have declared no conflicts of interest.

9047Background: Atezo (anti–PD-L1) + bev (anti-VEGF) + chemo prolonged PFS vs bev + chemo in patients (pts) with 1L nonsquamous mNSCLC in the randomized, Phase III IMpower150 study. PRO data, inclu...

We review the results of the 1988 multi-wavelength campaign on the late-type eclipsing binary YY Geminorum. Observations include: broad-band optical and near infra-red photometry, simultaneous optical and ultraviolet (IUE) spectroscopy, X-ray (Ginga) and radio (VLA) data. From models fitted to the optical light curves, fundamental physical parameters have been determined together with evidence for transient maculations (spots) located near quadrature longitudes and intermediate latitudes. Eclipses were observed at optical, ultraviolet and radio wavelengths. Significant drops in 6cm radio emission near the phases of both primary and secondary eclipse indicate relatively compact radio emitting volumes that may lie between the binary components. IUE observations during secondary eclipse are indicative of a uniform chromosphere saturated with MgII plage-type emission and an extended volume of Ly$\alpha$ emission. Profile fitting of high-dispersion H alpha spectra confirms the chromospheric saturation and indicates significant H$\alpha$ opacity to heights of a few percent of the photospheric radius. There is evidence for an enhanced H alpha emission region visible near phase 0.25-0.35 which may be associated with a large spot on the primary and with two small optical flares which were also observed at other wavelengths: one in microwave radiation and the other in X-rays. For both flares, L_X/L_opt is consistent with energy release in closed magnetic structures., Comment: 17 pages, 10 figures

In this trial, stopping bevacizumab after completion of induction chemotherapy was associated with a shorter time to progression, but no statistically significant difference in overall survival compared with the bevacizumab continuation strategy. Non-inferiority could not be demonstrated. Treatment costs are substantially higher for continuous bevacizumab treatment. Background Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer (mCRC) patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after completing first-line chemotherapy. Patients and methods In an open-label, phase III multicentre trial, patients with mCRC without disease progression after 4–6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned to continuing bevacizumab at a standard dose or no treatment. CT scans were done every 6 weeks until disease progression. The primary end point was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significance level of 10% and a statistical power of 85%. Results The intention-to-treat population comprised 262 patients: median follow-up was 36.7 months. The median TTP was 4.1 [95% confidence interval (CI) 3.1–5.4] months for bevacizumab continuation versus 2.9 (95% CI 2.8–3.8) months for no continuation; HR 0.74 (95% CI 0.58–0.96). Non-inferiority could not be demonstrated. The median overall survival was 25.4 months for bevacizumab continuation versus 23.8 months (HR 0.83; 95% CI 0.63–1.1;P = 0.2) for no continuation. Severe adverse events were uncommon in the bevacizumab continuation arm. Costs for bevacizumab continuation were estimated to be ∼30 000 USD per patient. Conclusions Non-inferiority could not be demonstrated for treatment holidays versus continuing bevacizumab monotheray, after 4–6 months of standard first-line chemotherapy plus bevacizumab. Based on no impact on overall survival and increased treatment costs, bevacizumab as a single agent is of no meaningful therapeutic value. More efficient treatment approaches are needed to maintain control of stabilized disease following induction therapy. Clinical trial registration ClinicalTrials.gov, number NCT00544700.

Corresponding Author: Michael Schmuecking, MD E-Mail: michael.schmuecking@insel.ch Inclusion criteria: Informed consent, histologically proven NSCLC stage I or hypermetabolic oligometastatic lung lesions. Peripheral or central localization, maximal tumor diameter of 45mm. Karnofsky index > 60%. Medically inoperable. Moving of the lung lesion during breathing less than 5mm as detected by 4D-CT. Initial staging: whole body 18F-FDG PET/CT in radiation treatment position, MRI of the brain. Optional for staging: 18F-FDG PET/CT of the lung in breath hold technique in radiation treatment position. Radiation treatment planning: 4D-CT and angio-CT in radiation treatment position for target volume delineation. BodyFIX® vacuum cushions for comfortable, accurate and reproducible patient positioning during radiation treatment. Using 4DCT for target volume delineation, a Boolean operation was used to sum the multiple gross target volumes (GTV) delineated in diagnostic lung window to form an internal target volume (ITV). The planning target volume was derived by a three-dimensional isotropic expansion of the ITV by 5mm to account for both microscopic extension and daily setup errors. Using non-gated PET/CT (frame mode) for target volume delineation of the ITV the iso-line of SUV 2.5 was used or the tumor/background algorithm as proposed by Nestle et al. JNM 2005. For 16/22 lung lesions the prescription dose was 5 x 12 Gy, for 1/22 centrally located lung lesion the prescription dose was 5 x 10 Gy, for the initial 5/22 lesions the prescription dose was 5 x 7 Gy. For all patients the prescription isodose was the 80% line (prescription line identical with the planning target volume). Maximal time for follow-up: 21 months, mean time for follow-up: 13 months. By design, stereotactic body radiotherapy (SBRT) is applied to small treatment volumes, using fewer but significantly higher dose fractions, and steep dose gradients – all of which act to maximize cell kill and minimize the risk of damage to the surrounding normal tissues.

Aim: Bevacizumab is a monoclonal antibody directed against the vascular endothelial growth factor (VEGF). The previous phase II trial ABIGAIL (Reck, 2010) suggested circulating VEGF as a prognostic, but not predictive, biomarker for patients (pts) with non-small cell lung cancer (NSCLC) treated with bevacizumab. We prospectively measured VEGF in the multicenter phase II trial SAKK19/09 (NCT01116219). Methods: SAKK19/09 enrolled 77 evaluable patients (pts) with previously untreated, advanced nonsquamous NSCLC and EGFR wild type. Pts received 4 cycles of cisplatin 75mg/m2 (or carboplatin AUC5), pemetrexed 500mg/m2 and bevacizumab 7.5mg/kg, followed by maintenance therapy with pemetrexed and bevacizumab until progression by RECIST1.1. Follow-up CT scans were performed every 6 weeks until week 54 and every 12 weeks thereafter. Baseline EDTA blood samples were sent by same-day courier to the central laboratory for centrifugation, aliquoting, and freezing. Upon completion of enrollment, aliquots were thawed, and VEGF quantification was performed centrally using Luminex® Performance Assay Human Base Kit A (RD 95%CI: 1.43- 4.57; p = 0.0015) and OS (8.7 vs 17.5 months, HR = 2.67; 95%CI: 1.37-5.20; p = 0.0041), but not with best response rate (p = 0.2256). Conclusions: Consistent with the ABIGAIL trial, circulating VEGF was prognostic, but not predictive for response, in the current trial. Further work is ongoing to identify potentially predictive biomarkers for bevacizumab, using comprehensive proteomic analyses. Disclosure: S.I. Rothschild: I received honoraria for the participation in advisory boards from Eli Lilly and Roche and for presentations at scientific symposiums sponsored by Roche; O. Gautschi: Honoraria for advisory boards of Eli Lilly and Roche; R. Cathomas: Advisory board member: Eli Lilly. All other authors have declared no conflicts of interest.

7503 Background: For stage III/N2 NSCLC neoadjuvant chemotherapy (NCT) followed by radical surgery is one standard treatment approach. In our previous trial, this strategy led to a median survival of 33 months (Betticher et al. JCO 2003). We now investigated whether the addition of preoperative radiotherapy (RT) would improve outcome. We report the results of a planned interim analysis on data of the first 219 patients (pts). The trial was closed to accrual in December 2012 due to futility after enrollment of 232 of 240 planned pts. Methods: Pts with pathologically proven, resectable stage IIIA/N2 NSCLC, performance status 0-1, adequate heart, kidney, liver and bone marrow function were randomized 1:1 to receive 3 cycles of NCT (cisplatin 100 mg/m2 and docetaxel 85 mg/m2 d1, q3weeks) followed by accelerated concomitant boost RT (44 Gy/22 fractions in 3 weeks) or NCT alone, with subsequent surgery for all pts. The primary endpoint was event-free survival (EFS). Results: 23 centers included 219 pts. Median age was 60 years. Pts characteristics were well balanced. Toxicity to CT was substantial, but 91% completed 3 cycles of NCT. RT-induced grade 3 esophagitis was seen in 5 pts, grade 3 skin toxicity in 2 pts. One pt in each treatment arm died during NCT, there was one postoperative death (arm NCT alone). The efficacy results are summarized below, all comparisons are statistically non-significant. Conclusions: This is the first completed phase III trial to investigate the value of the addition of neoadjuvant radiotherapy to CT and surgery. RT did not improve EFS or survival, nor did it reduce the local failure rate. Nevertheless, the overall survival rates of our neoadjuvant chemotherapy strategy confirm our previous report, and are among the best results reported to date in a multicenter setting. Clinical trial information: NCT00030771. [Table: see text]

3503 Background: Chemotherapy plus bevacizumab is a standard option for first-line treatment in metastatic colorectal cancer patients. We assessed whether no continuation is non-inferior to continuation of bevacizumab after stop of first-line chemotherapy. Methods: In an open-label, phase 3 multicenter study conducted in Switzerland, patients with unresectable metastatic colorectal cancer having non-progressive disease after 4-6 months of standard first-line chemotherapy plus bevacizumab were randomly assigned in a 1:1 ratio to continuing bevacizumab (7.5 mg/kg every 3 weeks) or no treatment. CT scans were done every 6 weeks between randomization and disease progression. The primary endpoint was time to progression (TTP). A non-inferiority limit for hazard ratio (HR) of 0.727 was chosen to detect a difference in TTP of 6 weeks or less, with a one-sided significant level of 10% and a statistical power of 85%. Results: The per-protocol population comprised 262 patients. Median follow-up is 28.6 months (range, 0.6-54.9 months). Median TTP was 17.9 weeks (95% CI 13.3-23.4) for bevacizumab continuation and 12.6 weeks (95% CI 12.0-16.4) for no continuation; HR 0.72 (95% CI 0.56-0.92). Median progression free-survival and overall survival, both measured from start of first-line treatment, was 9.5 months and 24.9 months for bevacizumab continuation and 8.5 months (HR 0.73 (95% CI 0.57 - 0.94)) and 22.8 months (HR 0.87 (95% CI 0.64 – 1.18)) for no continuation. Median time from randomization to second-line treatment was 5.9 months for bevacizumab and 4.8 for no continuation. Grade 3-4 adverse events in the bevacizumab continuation arm were uncommon. Conclusions: Non-inferiority could not be demonstrated. The 95% confidence intervals for the TTP HR indicate superiority of bevacizumab continuation after stop of first-line chemotherapy. The median differences in TTP and in time between randomization and start of second-line treatment were of moderate magnitude being less than 6 weeks. The results of an accompanying cost analysis will be presented at the meeting. Clinical trial information: NCT00544700.

7022 Background: Selecting carboplatin or cisplatin in the treatment of poor prognosis and/or extensive stage SCLC remains controversial. We performed an IPD meta-analysis from published randomized...

The large-amplitude δ Scuti star CY Aqr was observed from sites in the U.S.A., South Africa and Australia during August 1988. Coates et al. (1991) published 48 new times of maximum light derived from these observations and assembled, from the literature, previous times of maximum light. It is clear that the period of the star is changing with the balance of evidence favouring discrete changes in 1951 and 1966, rather than a continuous change.It has been suggested by Fitch (1973) and Else (1972), from an analysis of the observations of Zissell (1968), that there is a secondary frequency present in CY Aqr. Coates et al. (1992) have analysed both the 1988 observations and those of Zissell. After subtracting the primary frequency and its harmonics, they find no stable secondary frequency above the noise level of two millimagnitudes.

Thirty-two patients treated with primary cesarean hysterectomy for carcinoma in situ of the cervix diagnosed during pregnancy are reported. This approach has been offered to selected patients who for many reasons, primarily social, have been unable to return to the hospital after vaginal delivery for completion of therapy. The fetal outcome and maternal complications have been acceptable and the operative specimens have been adequate for treatment of the disease process.

Elective cesarean sections performed on the obstetric service at the University of Arkansas Medical Center were reviewed for the period January 1, 1970, through December 31, 1974. The purpose of the review was to compare operative and postoperative complications of cesarean section, cesarean section and tubal ligation, and cesarean section and elective hysterectomy. A total of 1,255 cesarean sections were performed of which 207 (17 per cent) were associated with tubal ligation and 242 (18 per cent) with hysterectomy. Elective cesarean hysterectomies were performed for elective sterilization (68 per cent), for medically indicated sterilizations (11 per cent), or for definitive treatment of uterine pathology (21 per cent). All cesarean sections were obstetrically indicated with the exception of 34 primary cesarean hysterectomies performed as definitive treatment of carcinoma in situ of the cervix. The operative procedures were compared in regard to the following characteristics or complications: operating time; incidence of blood transfusions, urinary tract injuries, postoperative bleeding, febrile morbidity, and other postoperative complications; and postoperative hospital days.

Multisite photoelectric b and V photometry of the δ Scuti variable θ2(78) Tau has been obtained on three continents. Five close pulsation frequencies (13.22965, 13.48073, 13.69360, 14.31764 and 14.61454 cycles per day) with visual amplitudes between 0.001 and 0.007 mag were found. The four frequencies found in the previous campaign were confirmed. All three main data sets (1982-1986) are in excellent agreement with each other and fit the solution to ±0.0028 mag per single measurement. Over the four years the amplitudes and frequencies of pulsation were constant.

The spatial structure of the luminous peculiar galaxy Arp 220 has been investigated in the far infrared. The results reveal that most of the luminosity is from a source less than 3 kpc in extent, located in the nuclear region of the galaxy. The size constraints yield a lower limit of 0.05 for the 100 micron optical depth, implying a hydrogen column density over 5 x 10 to the 22nd/sq cm. New optical images confirm that the double-lobed optical appearance results from strong absorption across the true nucleus. Arp 220 exhibits three primary features which provide strong evidence for an external source of energy: (1) a chaotic and highly asymmetric galactic halo; (2) a large internal velocity dispersion in CO and H I; and (3) extreme compression of gas and dust. These features are natural consequences of previously proposed models which invoke a direct galactic collision and merger, and are unlikely to result from a long-range tidal interaction with the neighboring galaxy IC 4554.