A collection of research papers published by the staff of The Christie NHS Foundation Trust between 1999 to present day. The collection is intended to back date all publications published since 1999. Older papers may be submitted by request to the Kostoris Library.

 

Recent Submissions

  • A retrospective clinical review of drug induced interstitial lung disease at a tertiary cancer centre.

    Walker, F; Broadbent, Rachel; Taylor, Benjamin; Tenant, Sean; Linton, Kim M; University of Manchester, Manchester (2018)
    Introduction: Drug induced interstitial lung disease (DIILD) is a well-recognised complication of cancer therapy with an unknown incidence. There are no standardised diagnostic criteria and management is variable. We retrospectively reviewed the clinical presentation, aetiology, management and outcomes for consecutive cases presenting to The Christie NHS Trust to inform future practice and areas for research. Methods: CT thorax requests and reports between 1/1/15 and 31/12/16 were screened for the terms ‘pneumonitis’ or ‘drug induced’. Patient demographics, clinical symptoms, diagnosis, cancer treatment, DIILD management and outcome data were collected. CT images were independently reviewed by a specialist radiologist and cases re-classified as ‘probable’, ‘possible’ or ‘unlikely’ for DIILD based on imaging features. Results: 199 CT thorax reports were identified. Duplicates (n=69) and radiotherapy-only treated cases were removed (n=11). 119 cases were re-classified as probable (n=22), possible (n=16) or unlikely (n=81. DIILD was clinically suspected in ~50% of cases, but symptoms were non-specific. Everolimus, bleomycin, pembrolizumab, gefitinib and paclitaxel were the most common causative drugs. Management varied widely. 90% of DIILD patients had treatment withdrawn, 50% were hospitalised and 74% received corticosteroids. Of symptomatic patients, 63% resolved, mostly within 3 months. All-cause mortality was 16%. Conclusions: Results highlight important unmet clinical and research needs to develop management protocols to unify practice and CT imaging biomarkers to improve diagnostic accuracy and clinical outcomes.
  • Pneumocystis jirovecii pneumonia (PJP) in lymphoma patients, a tertiary cancer centre review.

    Adderley, Helen; Syed, J; Cove-Smith, Laura; Linton, Kim M; The Christie Hospital NHS Foundation Trust, Manchester (2018)
    Background: PJP causes atypical pneumonia in immunocompromised patients with significant morbidity and mortality. There are no PJP management guidelines for non HIV populations and mortality is significantly higher in patients without HIV (34-39%) compared to HIV patients (6-7%). Aims and Objectives: To describe risk factors for PJP in lymphoma patients, management and clinical outcomes. Methods: We performed a retrospective case note review of PJP positive lymphoma patients at the Christie Hospital NHS Foundation Trust from January 2010-January 2016. Standards identified were that all patients receiving > 2 weeks of ? 20mg prednisolone daily should receive prophylaxis. All hypoxic patients with confirmed PJP should receive appropriate steroids. Results: 41 patients were identified: 27% Hodgkin lymphoma, 73% non Hodgkin lymphoma. Potential identifiable risks were lymphopenia (all grades ?= 95%; grade 3-4 = 38%), steroid use (61% of patients, majority for <1 week), recent immunochemotherapy (60% on treatment at diagnosis of PJP), and lack of required prophylaxis (20% of patients). 32% developed PJP despite use of prophylactic co-trimoxazole or azithromycin. 64% completed 21 days of treatment and 30- day mortality was 10%. Conclusions: PJP occurs in lymphoma patients despite prophylaxis and risks are unclear, especially as most patients are lymphopenic and/ or treated with short course steroids. We developed extended guidelines for patients recommending PJP prophylaxis for those receiving purine analogue chemotherapy, ?20mg prednisolone or equivalent daily for > 2 weeks and patients with lymphopenia ?0.5 and CD4 ?200. Results will be prospectively evaluated with scope for a national audit.
  • Patient perceptions of the impact of treatment (surgery and radiotherapy) for soft tissue sarcoma

    Hewitt, L; Powell, R; Zenginer, K; Coyle, Catherine; Murray, H; Cooper, L; Gregory, J; School of Health Sciences & Manchester Centre for Health Psychology, University of Manchester, Manchester (2019)
    Background and Objectives. Treatment for soft tissue sarcoma (STS) is challenging for patients. This study aimed to gain an in-depth understanding of patients’ experiences of STS treatment, including whether the sequence of treatment (preoperative or postoperative radiotherapy) influences patient perceptions. Methods. Face-to-face semi-structured interviews were conducted with nineteen patients who had been treated for STS with surgery and radiotherapy between 2011 and 2016. Topics discussed included perceptions of treatment, social support, and coping mechanisms. Qualitative, inductive, thematic analysis was conducted and structured using the Framework approach. Results. Treatment sequence itself did not appear to cause concern, but uncertainty regarding treatment and side effects could negatively impact participants. Social relationships and individual coping strategies influenced participants’ experiences of treatment. Conclusions. Participants’ perceptions of the treatment process varied; the experience was highly individual. It is important to ensure individual psychosocial and information needs are met. In particular, the removal of uncertainty regarding treatment is important in supporting patients undergoing treatment for soft tissue sarcoma.
  • An open-label, multicentre safety study of vemurafenib in patients with BRAF(V600)-mutant metastatic melanoma: final analysis and a validated prognostic scoring system.

    Larkin, J; Brown, MP; Arance, AM; Hauschild, A; Queirolo, P; Del, Vecchio, M; Ascierto, PA; Krajsova, I; Schachter, J; Neyns, B; Garbe, C; Sileni, VC; Mandala, M; Gogas, H; Espinosa, E; Hospers, G; Lorigan, Paul C; Nyakas, M; Guminski, A; Liszkay, G; Rutkowski, P; Miller, W; Donica, M; Makrutzki, M; Blank, C; The Royal Marsden NHS Foundation Trust, London (2019)
    BACKGROUND: The oncogenic BRAF inhibitor vemurafenib improves outcomes for patients with advanced BRAFV600 mutation-positive melanoma compared with cytotoxic chemotherapy. Vemurafenib is now approved for use in this patient population. PATIENTS AND METHODS: In this open-label, multicentre study, patients with previously treated or untreated melanoma and the BRAFV600 mutation received vemurafenib 960 mg twice daily. The primary endpoint was safety. In a post hoc analysis, overall survival (OS) was analysed according to a prognostic scoring system developed using Eastern Cooperative Oncology Group performance status, existence of brain metastases and baseline serum lactate dehydrogenase level. The index was validated using data from patients treated with vemurafenib or dacarbazine in three clinical trials and data from patients treated with vemurafenib plus cobimetinib in two studies. The study is registered with ClinicalTrials.gov (NCT01307397). RESULTS: Between March 2011 and January 2013, 3224 patients were enrolled, and 3219 patients received ?1 dose of vemurafenib (safety population); median follow-up time was 33.4 months. Vemurafenib's long-term benefits were confirmed, and no new safety signals identified. The prognostic index showed between-group differences in OS, with tight, non-overlapping confidence intervals. Validation in a pooled group of 666 vemurafenib-treated clinical trial patients revealed a similar pattern; the pattern was similar in 280 patients treated with vemurafenib plus cobimetinib. CONCLUSIONS: Final results from the vemurafenib safety study confirm vemurafenib's tolerability in BRAFV600 mutation-positive patients and resemble those seen in real-world clinical practice. This index may be useful in patients on combination therapy and as a basis for further work.
  • The advanced prostate cancer consensus on a regional level - what can we learn?

    Omlin, A; Gillessen, Silke; Department of Medical Oncology and Haematology, Cantonal Hospital St. Gallen, University of Bern, Bern, Switzerland (2019)
  • Cascaded systems analysis of a-Se/a-Si and a-InGaZnO TFT passive and active pixel sensors for tomosynthesis.

    Sengupta, A; Zhao, C; Konstantinidis, Anastasios; Kanicki, J; Solid-State Devices and Nanotechnology, Department of Electrical and Computer Engineering, University of Michigan, 1301 Beal Avenue Ann Arbor, MI 48109-2122 (2019)
    Medical imaging systems like full field digital mammography (FFDM) and digital breast tomosynthesis (DBT) commonly use amorphous selenium (a-Se) based passive pixel sensor (PPS) direct conversion x-ray detectors. On one hand, direct conversion detectors inherently offer better resolution characteristics in terms of a higher modulation transfer function (MTF), in comparison to the indirect CsI:Tl PPS x-ray imager. On the other hand, especially at lower doses, this superior performance of the direct imager is seldom retained in its detective quantum efficiency (DQE) curves. It is well known that a-Se PPS x-ray imagers suffer from high additive electronic noise originating from the from the amorphous silicon (a-Si) thin film transistor (TFT) array that is being used in the current back-plane technology. This degrades the noise power spectrum (NPS) and subsequently the overall DQE. To address this deficiency, we propose to replace the PPS back-plane by active pixel sensor (APS) back-plane technology, which has the potential to reduce the back-plane electronic noise by amplifying the input signal, especially at low doses. The proposed APS is based on amorphous In-Ga-Zn-O (a-IGZO) TFT technology, which can offer high mobility (5-20?cm2 V-1 s-1), low leakage current (<10-13 A) and low flicker noise (Hooge's parameter ? H ~ 1.5 [Formula: see text] 10-3), leading to better imager noise performance. To test our hypothesis, we used linear cascaded systems analysis to model the imaging performance (MTF, NPS and DQE) of the PPS and APS a-Se direct imagers. This model was first validated using experimentally measured data obtained for a 85 µm pixel pitch a-Se/a-Si TFT PPS imager. Using this model, we analyzed the noise performance of the direct a-Se and indirect CsI:Tl x-ray a-IGZO APS imagers at different dose and electronic noise levels. Obtained results clearly showed that lowering back-plane electronic noise can significantly improve the performance of the a-Se/a-IGZO TFT APS imager. Our simulated results showed that a higher DQE at lower radiation doses (maximum DQE of 0.6 can be achieved at an exposure level of 1 µGy) can be achieved with the a-Se detector, thereby making this combination a promising candidate for low dose applications like DBT.
  • Unmet needs in appendiceal neuroendocrine neoplasms.

    Toumpanakis, C; Fazio, N; Janson, E; Horsch, D; Pascher, A; Reed, N; O'Toole, D; Dijkum, E; Partelli, S; Rinke, A; Kos-Kudla, B; Costa, F; Pape, U; Grozinsky-Glasberg, S; Scoazec, J; The ENETS 2016 Munich Advisory Board Participants; Valle, Juan W; Neuroendocrine Tumour Unit, Royal Free Hospital, London (2019)
    Appendiceal neuroendocrine neoplasms (ANEN) are mostly discovered coincidentally during appendicectomy and usually have a benign clinical course; thus, appendicectomy alone is considered curative. However, in some cases, a malignant potential is suspected, and therefore additional operations such as completion right hemicolectomy are considered. The existing European Neuroendocrine Tumour Society (ENETS) guidelines provide useful data about epidemiology and prognosis, as well as practical recommendations with regards to the risk factors for a more aggressive disease course and the indications for a secondary operation. However, these guidelines are based on heterogeneous and retrospective studies. Therefore, the evidence does not seem to be robust, and there are still unmet needs in terms of accurate epidemiology and overall prognosis, optimal diagnostic and follow-up strategy, as well as identified risk factors that would indicate a more aggressive surgical approach at the beginning and a more intense follow-up. In this review, we are adopting a critical approach of the ENETS guidelines and published series for ANEN, focusing on the above-noted "grey areas".
  • Colorectal neuroendocrine neoplasms: areas of unmet need.

    Ramage, JK; Valle, Juan W; Dijkum, EJMN; Sundin, A; Pascher, A; Couvelard, A; Kloeppel, G; The ENETS 2016 Munich Advisory Board Participants; Department Gastroenterology, Hampshire Hospitals NHS Trust, Kings College Hospital ENETS centre of Excellence, Basingstoke (2019)
    The subject of colorectal neuroendocrine neoplasms (NENs), subdivided into well-differentiated NENs, termed neuroendocrine tumours (NETs; grade (G) 1 and 2), and poorly differentiated NENs, termed neuroendocrine carcinomas (NECs; G3) according to the 2010 World Health Organisation (WHO) classification, has arguably not had as much attention or study as NENs occurring in other sites. Colorectal NETs and NECs are however easier to study than many others since they are usually not difficult to remove and are increasingly detected because of intensified colorectal cancer screening and surveillance programmes. Colorectal NETs and NECs show site-specific heterogeneity with variable behaviour and different therapeutic options; these various aspects provide unique challenges. Because of bowel cancer screening programmes, colorectal NENs, like conventional adenocarcinomas, may be diagnosed at a stage that is associated with improved survival. In this article we intend to describe and define areas of unmet needs relating to the epidemiology, classification, pathology, diagnosis and therapy of colorectal NETs (including NETs G3), colorectal NECs, and finally, mixed adeno-neuroendocrine carcinomas (MANECs) by reviewing and discussing the relevant literature.
  • Unmet needs in high-grade gastroenteropancreatic neuroendocrine neoplasms (WHO G3).

    Sorbye, H; Baudin, E; Borbath, I; Caplin, M; Chen, J; Cwikla, JB; Frilling, A; Grossman, A; Kaltsas, G; Scarpa, A; Welin, S; Garcia-Carbonero, R; The ENETS 2016 Munich Advisory Board Participants; Valle, Juan W; Department of Oncology and Clinical Science, Haukeland University Hospital, Bergen, Norway (2019)
    Gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN) are classified based on morphology and graded based on their proliferation rate as either well-differentiated low-grade (G1 to G2) neuroendocrine tumors (NET) or poorly differentiated high-grade (G3) neuroendocrine carcinomas (NEC). Recently, a new subgroup of well-differentiated high-grade pancreatic tumors (NET G3) has been defined. The GEP NEN G3 group consisting of both NEC and NET G3 has recently been shown to be a quite heterogeneous patient group concerning prognosis and treatment benefit, depending on factors such as the primary tumor site, differentiation, proliferation rate, and molecular alterations. In this review we discuss the existing data on diagnostics, treatment, and biomarkers in this patient group, the unmet needs, and the future perspectives.
  • Immune monitoring after NKTR-214 plus nivolumab (PIVOT-02) in previously untreated patients with metastatic stage IV melanoma

    Diab, A; Tykodi, S; Curti, B; Cho, D; Wong, M; Puzanov, I; Lewis, K; Maio, M; Daniels, G; Spira, A; Tagliaferri, M; Hannah, A; Clemens, W; Imperiale, M; Bernatchez, C; Haymaker, C; Bentebibel, S; Zalevsky, J; Hoch, U; Fanton, C; Rizwan, A; Aung, S; Cattaruzza, F; Iaccucci, E; Sawka, D; Bilen, M; Lorigan, Paul C; Grignani, G; Larkin, J; Jang, S; Warzocha, E; Sznol, M; Hurwitz, M; Memorial Sloan Kettering Cancer Center, New York (2019)
  • Unmet medical needs in pulmonary neuroendocrine (carcinoid) neoplasms.

    Baudin, E; Hayes, A; Scoazec, J; Filosso, P; Lim, E; Kaltsas, G; Frilling, A; Chen, J; Kos-Kudla, B; Gorbunova, V; Wiedenmann, B; van, Dijkum E; Cwikla, J; Falkerby, J; Valle, Juan W; Kulke, M; Caplin, M; ENETS 2016 Munich Advisory Board Participants; Oncologie Endocrinienne et Médecine Nucléaire, Institut Gustave Roussy, Villejuif (2019)
    Pulmonary carcinoids (PCs) display the common features of all well-differentiated neuroendocrine neoplasms (NEN) and are classified as low- and intermediate-grade malignant tumours (i.e., typical and atypical carcinoid, respectively). There is a paucity of randomised studies dedicated to advanced PCs and management principles are drawn from the larger gastroenteropancreatic NEN experience. There is growing evidence that NEN anatomic subgroups have different biology and different responses to treatment and, therefore, should be investigated as separate entities in clinical trials. In this review, we discuss the existing evidence and limitations of tumour classification, diagnostics and staging, prognostication, and treatment in the setting of PC, with focus on unmet medical needs and directions for the future.
  • Unmet medical needs in metastatic lung and digestive neuroendocrine neoplasms.

    Capdevila, J; Bodei, L; Davies, P; Gorbounova, V; Jensen, R; Knigge, U; Krejs, G; Krenning, E; O'Connor, J; Peeters, M; Rindi, G; Salazar, R; Vullierme, M; Pavel, M; The ENETS 2016 Munich Advisory Board Participants; Valle, Juan W; Vall Hebron University Hospital, Vall Hebron Institute of Oncology (VHIO), Barcelona (2019)
    Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.
  • Unmet needs in functional and nonfunctional pancreatic neuroendocrine neoplasms.

    Jensen, R; Bodei, L; Capdevila, J; Couvelard, A; Falconi, M; Glasberg, S; Kloppel, G; Lamberts, S; Peeters, M; Rindi, G; Rinke, A; Rothmund, M; Sundin, A; Welin, S; Fazio, N; The ENETS 2016 Munich Advisory Board Participants; Valle, Juan W; Cell Biology Section, NIDDK, National Institutes of Health, Bethesda, Maryland (2019)
    Recently, the European Neuroendocrine Tumor Society (ENETS) held working sessions composed of members of the advisory board and other neuroendocrine neoplasm (NEN) experts to attempt to identify unmet needs in NENs in different locations or with advanced/poorly differentiated NENs. This report briefly summarizes the main proposed areas of unmet needs in patients with functional and nonfunctional pancreatic NENs.
  • Watch-and-wait strategy in rectal cancer - authors' reply.

    Chadi, S; Beets, G; Perez, R; Renehan, Andrew G; Division of Surgical Oncology and General Surgery, Princess Margaret Hospital and University Health Network, University of Toronto, Toronto, ON, Canada (2019)
    Background: Constitutional loss of function (LOF) single nucleotide polymorphisms (SNPs) in pattern recognition receptors FPR1, TLR3, and TLR4 have previously been reported to predict oxaliplatin benefit in colorectal cancer. Confirmation of this association could substantially improve patient stratification. Methods: We performed a retrospective biomarker analysis of the Short Course in Oncology Therapy (SCOT) and COIN/COIN-B trials. Participant status for LOF variants in FPR1 (rs867228), TLR3 (rs3775291), and TLR4 (rs4986790/rs4986791) was determined by genotyping array or genotype imputation. Associations between LOF variants and disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression, adjusted for confounders, using additive, dominant, and recessive genetic models. All statistical tests were two-sided. Results: Our validation study populations included 2929 and 1948 patients in the SCOT and COIN/COIN-B cohorts, respectively, of whom 2728 and 1672 patients had functional status of all three SNPs determined. We found no evidence of an association between any SNP and DFS in the SCOT cohort, or with OS in either cohort, irrespective of the type of model used. This included models for which an association was previously reported for rs867228 (recessive model, multivariable-adjusted hazard ratio [HR] for DFS in SCOT?=?1.19, 95% confidence interval [CI]?=?0.99 to 1.45, P?=?.07; HR for OS in COIN/COIN-B?=?0.92, 95% CI?=?0.63 to 1.34, P?=?.66), and rs4986790 (dominant model, multivariable-adjusted HR for DFS in SCOT?=?0.86, 95% CI?=?0.65 to 1.13, P?=?.27; HR for OS in COIN/COIN-B?=?1.08, 95% CI?=?0.90 to 1.31, P?=?.40). Conclusion: In this prespecified analysis of two large clinical trials, we found no evidence that constitutional LOF SNPs in FPR1, TLR3, or TLR4 are associated with differential benefit from oxaliplatin. Our results suggest these SNPs are unlikely to be clinically useful biomarkers.
  • Brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma (ECHELON-2): a global, double-blind, randomised, phase 3 trial.

    Horwitz, S; O'Connor, O; Pro, B; Illidge, Timothy M; Fanale, M; Advani, R; Bartlett, N; Christensen, J; Morschhauser, F; Domingo-Domenech, E; Rossi, G; Kim, W; Feldman, T; Lennard, A; Belada, D; Illes, A; Tobinai, K; Tsukasaki, K; Yeh, S; Shustov, A; Huttmann, A; Savage, K; Yuen, S; Iyer, S; Zinzani, P; Hua, Z; Little, M; Rao, S; Woolery, J; Manley, T; Trumper, L; Aboulafia, D; Alpdogan, O; Ando, K; Arcaini, L; Baldini, L; Bellam, N; Bartlett, N; Yehuda, DB; Benedetti, F; Borchman, P; Bordessoule, D; Brice, P; Briones, J; Caballero, D; Carella, A; Chang, H; Cheong, J; Cho, S; Choi, I; Choquet, S; Colita, A; Congui, A; D'amore, F; Dang, N; Davison, K; De, Guibert S; Brown, P; Delwail, V; Demeter, J; di Raimondo, F; Do, Y; Domingo, E; Douvas, M; Dreyling, M; Ernst, T; Fay, K; Ferrero, S; Flinn, I; Forero-Torres, A; Fox, C; Friedberg, J; Fukuhara, N; Garcia-Marco, J; Cruz, J; Codina, J; Gressin, R; Grigg, A; Gurion, R; Haioun, C; Hajek, R; Hanel, M; Hatake, K; Hensen, R; Horowitz, N; Huttmann, A; Ishizawa, K; Islas-Ohlmayer, M; Jacobsen, E; Janakiram, M; Jurczak, W; Kaminski, M; Kato, K; Kirgner, I; Kuo, C; Lazaroiu, M; Le, Du, K; Lee, J; Legouill, S; Larosee, P; Levi, I; Link, B; Maisonneuve, H; Maruyama, D; Mayer, J; McCarty, J; Mckay, P; Minami, Y; Mocikova, H; Morra, E; Munoz, J; Nagai, H; O'Connor, O; Opat, S; Pettengell, R; Pezzutto, A; Pfreundschuh, M; Pluta, A; Porcu, P; Quach, H; Rambaldi, A; Renwick, W; Reyes, R; Izquierdo, A; Ruan, J; Rusconi, C; Salles, G; Santoro, A; Sarriera, J; Savage, K; Shibayama, H; Suh, C; Sureda, A; Tanimoto, M; Taniwaki, M; Tilly, H; Trneny, M; Trumper, L; Tsukamoto, N; Vitolo, U; Walewski, J; Weidmann, E; Wilhelm, M; Witzens-Harig, M; Yacoub, A; Yamamoto, K; Yoon, S; Yun, H; Zain, J; Zinzan, P; Memorial Sloan Kettering Cancer Center, New York (2019)
  • Abiraterone acetate plus prednisone for the management of metastatic castration-resistant prostate cancer (mCRPC) without prior use of chemotherapy: report from a large, international, real-world retrospective cohort study.

    Boegemann, M; Khaksar, S; Bera, G; Birtle, A; Dopchie, C; Dourthe, L; Everaert, E; Hatzinger, M; Hercher, D; Hilgers, W; Matus, G; Alvarez, L; Antoni, L; Lukac, M; Pissart, G; Robinson, P; Elliott, Tony; Department of Urology, University of Muenster Medical Center, Albert-Schweitzer-Campus 1, GB A1, D-48149, Muenster, Germany (2019)
    BACKGROUND: With the recent introduction of novel treatment options, real-world data from patients with metastatic castration-resistant prostate cancer (mCRPC) are required to better understand the impact on routine clinical practice. This study primarily aimed to describe the time to treatment failure (TTF) of mCRPC patients treated with abiraterone acetate plus prednisone or the corticosteroid of choice (AAP) in the pre-chemotherapy setting. Other relevant outcomes, clinical and treatment characteristics of these patients were also evaluated. METHODS: This retrospective, observational study collected data from chemotherapy-naïve mCRPC patients treated with AAP from four European countries. Kaplan-Meier curves were used to estimate TTF, progression-free survival (PFS), and time to first skeletal-related event. The impact of baseline characteristics on TTF and PFS was explored using univariate and multivariate Cox proportional hazard models. Log-rank test was used to assess the potential role of duration of response to ADT in predicting response to AAP treatment. RESULTS: Data from 481 eligible patients (Belgium: 68; France: 61; Germany: 150; UK: 202) were analysed. At AAP initiation, the median age of patients was 75.0?years (interquartile range [IQR]: 69.0-81.0), and the median PSA was 56.2?ng/mL (IQR: 22.2-133.1), with over 50% of patients presenting an ECOG score of 0 or 1. Visceral metastases were present in 7.5% of patients; an exclusion criterion in the COU-AA-302 clinical trial. The median TTF with AAP was 10.0?months (95%CI: 9.2-11.1) and the median PFS was 10.8?months (95%CI: 9.6-11.8). Shorter TTF was significantly associated with higher ALP (>?119?units/L), higher PSA (>?56.2?ng/mL), or poorer ECOG PS scores at AAP initiation (p <?0.05). Patients with longer duration of response to ADT (?12?months) presented longer TTF and longer time to progression (p <?0.0001). CONCLUSIONS: This European real-world study provides valuable insights into the characteristics, treatment, and outcomes of chemotherapy-naïve patients with mCRPC who received AAP in routine clinical practice. Treatment effectiveness of AAP in the real-world is maintained despite patients having poorer clinical features at initiation than those observed in the COU-AA-302 trial population.
  • Mesenchymal stromal cells for acute graft-versus-host disease: response at 1 week predicts probability of survival.

    Galleu, A; Milojkovic, D; Deplano, S; Szydlo, R; Loaiza, S; Wynn, R; Marks, D; Richardson, D; Orchard, K; Kanfer, E; Tholouli, E; Saif, M; Sivaprakasam, P; Lawson, S; Bloor, Adrian; Pagliuca, A; Potter, V; Mehra, V; Snowden, J; Vora, A; Kishore, B; Hunter, H; Apperley, J; Dazzi, F; King's College London, London, UK (2019)
    Mesenchymal stromal cells (MSCs) have been successfully used for the treatment of steroid-resistant graft-versus-host-disease (GvHD). However, the lack of early predictors of clinical responses impacts on the time at which to add further treatment and consequently the design of informative clinical trials. Here, we present the UK experience of one of the largest cohorts of GvHD patients undergoing MSC infusions so far reported. We show that clinical responses assessed as early as 1 week after MSC infusion predict patients' overall survival. In our cohort, cell dose, patients' age and type of organ involvement are crucial factors associated with clinical responses.
  • Position of a panel of international lung cancer experts on the approval decision for use of durvalumab in stage III non-small cell lung cancer (NSCLC) by the Committee for Medicinal Products for Human Use (CHMP).

    Peters, S; Dafni, U; Boyer, M; De, R; Faivre-Finn, Corinne; Felip, E; Garrido, P; Girard, N; Guckenberger, M; Haanen, J; Le, P; Mornex, F; Ozsahin, M; Paz-Ares, L; Planchard, D; Raben, D; Ramalingam, S; Reck, M; Smit, E; Stahel, R; Stenzinger, A; Swanton, C; Vallone, S; Garassino, M; Oncology Department, Lausanne University and CHUV, Switzerland (2019)
  • Validation and reproducibility of changes in magnetic resonance imaging radiomic features in response to androgen deprivation therapy in patients with high-risk prostate cancer.

    Tharmalingam, Hannah; Beasley, William J; Alonzi, R; McWilliam, Alan; Hoskin, Peter J; Choudhury, Ananya; Mount Vernon Cancer Centre, Middlesex (2019)

View more