Explore the vast range of titles available.

Introduction/Background*Cervical cancer is the most common gynaecological malignancy worldwide. Despite strides in disease prevention with HPV (human papillomavirus) vaccination, and early detection of pre-cancerous changes, cervical cancer is nonetheless associated with high mortality. Survival is strongly linked to initial FIGO (International Federation of Gynaecology and Obstetrics) disease stage at diagnosis. In 2018, the FIGO staging criteria for cervical cancer were revised to include lymph node status, with positive nodes upstaging patients to stage 3C disease. This resulted in a retrospective stage migration for many patients. This study aims to analyse the effect of stage migration in cervical cancer on disease survival and systemic recurrence.MethodologyData from a cohort of 76 cervical cancer patients from the University Hospital of Derby and Burton NHS Trust diagnosed and treated with chemoradiation and brachytherapy from 2012–2017 were collected. Patients with positive lymph nodes at diagnosis were assigned a new stage based on the current 2018 FIGO criteria and subsequently compared to patients whose stage at initial diagnosis remained unchanged.Result(s)*46% of patients were assigned a new higher stage based on lymph node status at diagnosis as per 2018 FIGO staging. An approximate 2.5x increase in cancer-related mortality was seen amongst those who had stage migrated versus those who remained the same stage (37.14% versus 14.63%, p=0.024). Furthermore, a non-significant difference was seen in rates of systemic recurrence between the two groups, with around twice as many of the lymph node positive patients recurring within the timeframe of the study (40.00% compared with 19.51%, p=0.05).Conclusion*These results reinforce the importance in the inclusion of lymph node status within 2018 FIGO staging criteria owing to the significant effect upon mortality in those who had stage migrated. The poorer prognosis and survival in the stage migration group also highlights the need for aggressive intervention in those with positive lymph nodes.

Introduction/BackgroundBoth CHORUS and EORTC 55971 demonstrated no difference in OS/PFS between PDS OR IDS. However, both trials have been criticised due to low surgical quality. Retrospective reviews have suggested differences in OS/PFS/PFI.AimTo investigate if PDS or IDS, affects the OS, PFS or PSI in a cohort of AOC patients receiving high quality surgery.MethodologyAll patients with AOC treated between 02/2014–01/2019 obtaining complete cytoreduction with intermediate/high surgical complexity. Recurrence was defined on radiological/CA125 findings. Platinum sensitivity was defined according to international standards.Results53 patients were identified (32 PDS and 21 IDS) with full recurrence data. No difference was seen in Age or Surgical complexity. 25 patients had recurred (15 PDS and 10 IDS). No difference was seen between groups in OS or PFS. Median survival was not yet reached. 56% were alive at 41months and 52% alive at 48 months in PDS and IDS groups respectively. Median PFS was 20.7 months in both groups. PFI did not differ between PDS or IDS patients.ConclusionThis study supports the findings of previous randomised studies that no difference persists in OS, PFS or PSI in patients undergoing PDS or IDS.DisclosureNothing to disclose.

Introduction/BackgroundUltra-radical procedures, including splenectomy, are utilised during cytoreductive surgery in AOC to treat disease that would not be removed with standard procedures, the intention being to increase complete cytoreduction rates. Hypothetically the performance of splenectomy may independently be a marker for worse survival due to detrimental effects on immune function or its complications.MethodologyA retrospective review of all consecutive patients undergoing cytoreductive surgery for AOC between 16/05/2013–6/02/2019. Survival, complications and surgical parameters were recorded. Propensity scored matching (PSM) was performed, allowing comparison between splenectomy patients with both standard and ultra-radical surgery without splenectomy.Results151 patients were identified within a 71 month time period. Of these 100 underwent standard and 51 underwent ultra-radical surgery. 22 patients received splenectomy (14.5%)No difference was seen in Overall survival (OS) between all patients (median OS 34 months (95% CI 25.9–41.1) and patients undergoing splenectomy (median OS not yet reached) (p≥0.05).When comparing UR only patients, neither arm reached median OS; HR=1.8 (0.64–5.3), p>0.05.After PSM for grade, stage, age and cytoreduction, no significant difference in splenectomy versus non-splenectomy patients (3-year survival 54% compared to 56% (hazard ratio - 1.1 (95% CI 0.39–3.2). (P>0.05).When matching only to Ultra radical controls, no significant difference in OS was seen with median OS not reached in either arm (HR - 2.6(0.55–13) p>0.05).Splenectomy specific complications were seen in 3 patients; one pancreatic tail injury, one left pleural effusion and one cases of streptococcal pharyngitis during chemotherapy.No cases of overwhelming post splenectomy infection were identified.ConclusionSplenectomy does not negatively impact the complication rates of surgery or survival; and should not be feared by gynaecological oncologist undertaking ultra-radical surgery for AOC.DisclosureNothing to disclose.

Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival. The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK. Adults (aged ≥18 years) with locally advanced cervical cancer (FIGO 2008 stage IB1 disease with nodal involvement, or stage IB2, IIA, IIB, IIIB, or IVA disease) were randomly assigned (1:1), by minimisation, using a central electronic system, to standard cisplatin-based chemoradiotherapy (once-a-week intravenous cisplatin 40 mg/m2 for 5 weeks with 45·0–50·4 Gy external beam radiotherapy delivered in 20–28 fractions plus brachytherapy to achieve a minimum total 2 Gy equivalent dose of 78–86 Gy) alone or induction chemotherapy (once-a-week intravenous carboplatin area under the receiver operator curve 2 and paclitaxel 80 mg/m2 for 6 weeks) followed by standard cisplatin-based chemoradiotherapy. Stratification factors were recruiting site, stage, nodal status, three-dimensional conformal radiotherapy or intensity modulated radiotherapy, age, tumour size, and histology (squamous vs non-squamous). Primary endpoints were progression-free survival and overall survival within the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT01566240, and EUDRACT, 2011-001300-35. Between Nov 8, 2012, and Nov 17, 2022, 500 eligible patients were enrolled and randomly assigned to the chemoradiotherapy alone group (n=250) or the induction chemotherapy with chemoradiotherapy group. Of 500 patients, 354 (70%) had stage IIB disease and 56 (11%) stage IIIB disease. Pelvic lymph nodes were positive in 215 (43%) patients. 230 (92%) patients who received induction chemotherapy had at least five cycles. Median interval between induction chemotherapy and chemoradiotherapy was 7 days. Four or more cycles of cisplatin were given to 212 (85%) participants in the induction chemotherapy with chemoradiotherapy group and to 224 (90%) of participants in the chemoradiotherapy alone group. 462 (92%) participants received external beam radiotherapy and brachytherapy with a median overall treatment time of 45 days. After a median follow-up of 67 months, 5-year progression-free survival rates were 72% in the induction chemotherapy with chemoradiotherapy group and 64% in the chemoradiotherapy alone group with a hazard ratio (HR) of 0·65 (95% CI 0·46–0·91, p=0·013). 5-year overall survival rates were 80% in the induction chemotherapy with chemoradiotherapy group and 72% in the chemoradiotherapy alone group, with an HR of 0·60 (95% CI 0·40–0·91, p=0·015). Grade 3 or greater adverse events were reported in 147 (59%) of 250 individuals in the induction chemotherapy with chemoradiotherapy group versus 120 (48%) of 250 individuals in the chemoradiotherapy alone group. Short-course induction chemotherapy followed by chemoradiotherapy significantly improves survival of patients with locally advanced cervical cancer. Cancer Research UK and University College London–University College London Hospitals Biomedical Research Centre.

PARTNER is a prospective, phase II–III, randomized controlled clinical trial that recruited patients with triple-negative breast cancer 1 , 2 , who were germline  BRCA 1 and BRCA2 wild type 3 . Here we report the results of the trial. Patients ( n  = 559) were randomized on a 1:1 basis to receive neoadjuvant carboplatin–paclitaxel with or without 150 mg olaparib twice daily, on days 3 to 14, of each of four cycles (gap schedule olaparib, research arm) followed by three cycles of anthracycline-based chemotherapy before surgery. The primary end point was pathologic complete response (pCR) 4 , and secondary end points included event-free survival (EFS) and overall survival (OS) 5 . pCR was achieved in 51% of patients in the research arm and 52% in the control arm ( P  = 0.753). Estimated EFS at 36 months in the research and control arms was 80% and 79% (log-rank P  > 0.9), respectively; OS was 90% and 87.2% (log-rank P  = 0.8), respectively. In patients with pCR, estimated EFS at 36 months was 90%, and in those with non-pCR it was 70% (log-rank P  < 0.001), and OS was 96% and 83% (log-rank P  < 0.001), respectively. Neoadjuvant olaparib did not improve pCR rates, EFS or OS when added to carboplatin–paclitaxel and anthracycline-based chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2 wild type. ClinicalTrials.gov ID: NCT03150576 . A study details the results of the PARTNER trial, a prospective, randomized controlled trial of the use of neoadjuvant olaparib with carboplatin–paclitaxel chemotherapy in patients with triple-negative breast cancer who were germline BRCA1 and BRCA2  wild type.

How many stars have formed in the Universe, and when did they do so? These fundamental questions are difficult to answer because there are systematic uncertainties in converting the light we observe into the total mass of stars in galaxies. The Fermi-LAT Collaboration addressed these questions by exploiting the way that gamma rays from distant blazars propagate through intergalactic space, which depends on the total amount of light emitted by all galaxies. The collaboration found that star formation peaked about 3 billion years after the Big Bang (see the Perspective by Prandini). Although this is similar to previous estimates from optical and infrared observations, the results provide valuable confirmation because they should be affected by different systematic effects. Science , this issue p. 1031 ; see also p. 995 Intergalactic gamma rays are used to determine the star formation history of the Universe. The light emitted by all galaxies over the history of the Universe produces the extragalactic background light (EBL) at ultraviolet, optical, and infrared wavelengths. The EBL is a source of opacity for gamma rays via photon-photon interactions, leaving an imprint in the spectra of distant gamma-ray sources. We measured this attenuation using 739 active galaxies and one gamma-ray burst detected by the Fermi Large Area Telescope. This allowed us to reconstruct the evolution of the EBL and determine the star formation history of the Universe over 90% of cosmic time. Our star formation history is consistent with independent measurements from galaxy surveys, peaking at redshift z ~ 2. Upper limits of the EBL at the epoch of reionization suggest a turnover in the abundance of faint galaxies at z ~ 6.

IntroductionStudies purporting the safety of HRT in cervical cancer have predominantly included patients with squamous disease. Pathological studies have identified increasing estrogen receptor positivity in cervical adenocarcinomas. A recent small case-control study suggested a trend towards reduced survival following HRT use in adenocarcinomas. The objective of this study was to assess if HRT use in patients treated for cervical adenocarcinomas was detrimental to survival.MethodsA retrospective review of all women aged ≤50, with stage 1B-2B cervical adenocarcinoma diagnosed between 1/11/00–24/9/19. Women were categorized as: ovaries conserved (OVCON); or Iatrogenic menopause with (IM-HRT) or without (IM-NOHRT) HRT. HRT use was defined on an intention to treat basis. Statistical analysis was performed using Kaplan-Meier and Cox proportional hazards methods.Results58 women with mean age 38.6±6.5 yrs were included in the study. 25(43.1%) had OVCON, 12(20.7%) had IM-NOHRT and 21(36.2%) had IM-HRT. No menopause-associated deaths occurred. 5-year disease specific survival was 95% in OVCON, 95% in IM-HRT and 64% in IM-NOHRT (p = 0.041 and 0.016 between IM-NOHRT and IM-HRT and OVCON respectively). On multivariate analysis, adjusting for stage, grade, treatment approach and nodal status neither differences remained significant. 5-year progression free survival was 80% in OVCON, 91% in IM-HRT and 66% in IM-NOHRT but this was not statistically significant (p= 0.077).ConclusionsHRT or ovarian conservation does not appear to be detrimental to survival in cervical adenocarcinomas. In this small dataset, there is a trend towards improved survival with HRT. Larger studies are required to substantiate these findings.

The atmospheric Cherenkov gamma-ray telescope MAGIC, designed for a low-energy threshold, has detected very-high-energy gamma rays from a giant flare of the distant Quasi-Stellar Radio Source (in short: radio quasar) 3C 279, at a distance of more than 5 billion light-years (a redshift of 0.536). No quasar has been observed previously in very-high-energy gamma radiation, and this is also the most distant object detected emitting gamma rays above 50 gigaelectron volts. Because high-energy gamma rays may be stopped by interacting with the diffuse background light in the universe, the observations by MAGIC imply a low amount for such light, consistent with that known from galaxy counts.

Microquasars are binary star systems with relativistic radio-emitting jets. They are potential sources of cosmic rays and can be used to elucidate the physics of relativistic jets. We report the detection of variable gamma-ray emission above 100 gigaelectron volts from the microquasar LS I 61 + 303. Six orbital cycles were recorded. Several detections occur at a similar orbital phase, which suggests that the emission is periodic. The strongest gamma-ray emission is not observed when the two stars are closest to one another, implying a strong orbital modulation of the emission or absorption processes.