Payne H.,University College London |
Adamson A.,Hampshire Hospitals NHS Foundation Trust |
Bahl A.,Bristol Oncology and Haematology Center |
Borwell J.,Frimley Park Hospital NHS Foundation Trust |
And 7 more authors.
BJU International | Year: 2013
To review the published data on predisposing risk factors for cancer treatment-induced haemorrhagic cystitis (HC) and the evidence for the different preventive and therapeutic measures that have been used in order to help clinicians optimally define and manage this potentially serious condition. Despite recognition that HC can be a significant complication of cancer treatment, there is currently a lack of UK-led guidelines available on how it should optimally be defined and managed. A systematic literature review was undertaken to evaluate the evidence for preventative measures and treatment options in the management of cancer treatment-induced HC. There is a wide range of reported incidence due to several factors including variability in study design and quality, the type of causal agent, the grading of bleeding, and discrepancies in definition criteria. The most frequently reported causal factors are radiotherapy to the pelvic area, where HC has been reported in up to 20% of patients, and treatment with cyclophosphamide and bacillus Calmette-Guérin, where the incidence has been reported as up to 30%. Mesna (2-mercaptoethane sodium sulphonate), hyperhydration and bladder irrigation have been the most frequently used prophylactic measures to prevent treatment-related cystitis, but are not always effective. Cranberry juice is widely cited as a preventative measure and sodium pentosanpolysulphate as a treatment, although the evidence for both is very limited. The best evidence exists for intravesical hyaluronic acid as an effective preventative and active treatment, and for hyperbaric oxygen as an equally effective treatment option. The lack of robust data and variability in treatment strategies used highlights the need for further research, as well as best practice guidance and consensus on the management of HC. © 2013 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of British Association of Urological Surgeons.
PubMed | EORTC Headquarters, Hannover Medical School, Weston Park Hospital, Royal Marsden Hospital and 4 more.
Type: | Journal: European journal of cancer (Oxford, England : 1990) | Year: 2016
Anthracycline-based chemotherapy remains the mainstay of first-line treatment in metastatic or advanced soft-tissue sarcoma (STS). Age, performance status, tumour histology and tumour grade are recognised prognostic factors; however, the prognostic value of tumour response and tumour shrinkage is ill-defined.Patients recruited to the European Organisation for Research and Treatment of Cancer62012 trial with advanced intermediate or high-grade STS, who received at least one cycle of chemotherapy and one tumour assessment of response, were eligible for this study. Kaplan-Meier estimates of overall survival (OS) by tumour response were computed using a landmark approach after two, four, and six cycles of chemotherapy. The prognostic role of the kinetics of tumour response was analysed by Cox proportional hazards.Three hundred eighty-nine patients were included in this study. Compared to stable or responding patients, patients with progressive disease (PD) after two, four and six cycles of chemotherapy achieved a worse OS: hazard ratio [HR] 2.62 (95% confidence interval [CI] 1.72-4.00), p<0.001; HR 2.23 (95% CI 1.4-3.56), p=0.0001; and HR 3.16 (95% CI 1.96-5.08), p=0.0001, respectively. However, patients with stable or responding disease achieved similar OS outcomes. Correspondingly, patients with an increase in tumour size by 10% or more correlated with a worse OS in Cox proportional hazard analysis.No association between prognosis and amount of tumour shrinkage was detected. Interestingly, an increase in tumour size by at least 10% correlated with a worse OS, but re-defining PD as a 10% increase in tumour size did not translate into a better discrimination of survival outcomes for responders versus stable disease. Disease control rather than tumour response is a valuable end-point in advanced or metastatic STS receiving palliative anthracycline-based chemotherapy, supporting the use of time-to-event end-points in future STS trials.
Grimer R.,Royal Orthopaedic Hospital |
Athanasou N.,Nuffield Orthopaedic Center |
Gerrand C.,Freeman Hospital |
Judson I.,Royal Marsden |
And 5 more authors.
Sarcoma | Year: 2010
These guidelines have been developed in order to provide an overview and a set of broad-based key recommendations for the management of patients with bone sarcomas in the UK. They have taken into consideration the most up-to-date scientific literature along with the recent recommendations by the European Society of Medical Oncology. The principles of the NICE guidance on both improving outcomes for patients with sarcomas and improving outcomes with children and young people with cancer have been incorporated. As care evolves, it is acknowledged that these guidelines will need updating. The key recommendations are that bone pain or a palpable mass should always lead to further investigation and patients with clinicoradiological findings suggestive of a primary bone tumour should be sent to a reference centre. Patients should then have their care managed at such a specialist centre by a fully accredited multidisciplinary team. © 2010 Robert Grimer et al.
Weickhardt A.J.,Aurora University |
Doebele R.C.,Aurora University |
Purcell W.T.,Aurora University |
Bunn P.A.,Aurora University |
And 11 more authors.
Cancer | Year: 2013
BACKGROUND Crizotinib is a tyrosine kinase inhibitor active against ALK, MET, and ROS1. We previously reported that crizotinib decreases testosterone in male patients. The detailed etiology of the effect, its symptomatic significance, and the effectiveness of subsequent testosterone replacement have not been previously reported. METHODS Male cancer patients treated with crizotinib had total testosterone levels measured and results compared with non-crizotinib-treated patients. Albumin, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and/or luteinizing hormone (LH) were tracked longitudinally. A subset of patients had free testosterone levels measured and a hypogonadal screening questionnaire administered. Patients receiving subsequent testosterone supplementation were assessed for symptomatic improvement. RESULTS Mean total testosterone levels were -25% below the lower limit of normal (LLN) in 32 crizotinib-treated patients (27 of 32 patients below LLN, 84%) compared with +29% above LLN in 19 non-crizotinib-treated patients (6 of 19 below LLN, 32%), P =.0012. Levels of albumin and SHBG (which both bind testosterone) declined rapidly with crizotinib, but so did FSH, LH, and free testosterone, suggesting a centrally mediated, true hypogonadal effect. Mean free testosterone levels were -17% below LLN (19 of 25 patients below LLN, 76%). Eighty-four percent (16 of 19) with low free levels, and 79% (19/24) with low total levels had symptoms of androgen deficiency. Five of 9 patients (55%) with low testosterone given testosterone supplementation had improvement in symptoms, coincident with increases in testosterone above LLN. CONCLUSIONS Symptoms of androgen deficiency and free or total/free testosterone levels should be tracked in male patients on crizotinib with consideration of testosterone replacement as appropriate. © 2013 American Cancer Society.
Cananzi F.C.M.,Royal Marsden |
Judson I.,Sarcoma Unit |
Lorenzi B.,Royal Marsden |
Benson C.,Sarcoma Unit |
Mudan S.,Royal Marsden
European Journal of Surgical Oncology | Year: 2013
The introduction of receptor tyrosine kinase inhibitors (TKIs) has revolutionized the management of gastrointestinal stromal tumour (GIST). Strong evidence supports the use of imatinib as first-line treatment in metastatic or unresectable tumours and its efficacy in the post-operative adjuvant setting has been confirmed by phase III trials. There are a number of reports concerning the administration of imatinib in the pre-operative setting, however, the heterogeneity of the terminology used and the indications for pre-operative treatment make it difficult to determine the true value of pre-operative imatinib. Larger studies, or a phase III trial could be helpful but patient accrual and standardization of care could be difficult. We propose a pre-treatment classification of GIST in order to facilitate the comparison and collection of data from different institutions, and overcome the difficulties related to accrual. Moreover, in the current era of multidisciplinary treatment of GIST, an appropriate classification is mandatory to properly design clinical trials and plan stage-adapted treatment. © 2013 Elsevier Ltd. All rights reserved.
Antonia S.J.,H. Lee Moffitt Cancer Center and Research Institute |
Larkin J.,Royal Marsden |
Ascierto P.A.,Instituto Nazionale Tumori Fondazione G Pascale
Clinical Cancer Research | Year: 2014
Immuno-oncology is an evolving treatment modality that includes immunotherapies designed to harness the patient's own immune system. This approach is being studied for its potential to improve long-term survival across multiple tumor types. It is now important to determine how immunotherapies may be most effectively used to achieve the best possible patient outcomes. Combining or sequencing immunotherapies that target distinct immune pathways is a logical approach, with the potential to further enhance the magnitude of the antitumor immune response over single agents. Early clinical data in patients with melanoma treated with two immune checkpoint inhibitors, ipilimumab and nivolumab, suggest support for this combination approach. Numerous other combination approaches are being evaluated in early-phase clinical trials; however, their clinical activity remains unknown. Clinical experience to date has shown that when combining an immuno-oncology agent with an existing therapeutic modality, it is important to determine the optimal dose, schedule, and sequence. ©2014 American Association for Cancer Research.
Tam H.H.,Royal Marsden |
Collins D.J.,Institute of Cancer Research |
Wallace T.,Royal Marsden |
Brown G.,Royal Marsden |
And 2 more authors.
British Journal of Radiology | Year: 2012
Objectives: Segmental liver hyperintensity can be observed in malignant biliary obstruction on diffusion weighted MRI (DW-MRI). We describe MRI findings associated with this sign and evaluate whether DW-MRI segmental hyperintensity has any relationship with serum alanine aminotransferase (ALT) levels. Methods: The DW-MRI T 1 weighted, T 2 weighted and gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced T 1 weighted images obtained in 21 patients with hepatic malignancy, who demonstrated biliary obstruction and segmental hyperintensity on DW-MRI (b50-750 smm -2), were retrospectively reviewed by 2 readers blinded to clinical results. DW-MRI hyperintense liver segments were recorded as hypointense, isointense or hyperintense relative to normal liver on T 1/T 2 weighted imaging. It was also noted whether contrast enhancement was similar to that observed in normal liver or diminished in the hepatocellular phase. The mean apparent diffusion coefficient (ADC) value (×10 -3 s mm -2) of DW-MRI hyperintense segments, normal liver and tumour were compared using Student's t-test. The frequency of MRI findings was corroborated with serum ALT levels, which reflect hepatocyte injury. Results: DW-MRI hyperintense segments frequently showed T 1 hyperintensity (10/21), T 2 hyperintensity (19/21) and/or diminished contrast enhancement (15/21). Tumours showed significantly lower mean ADC values than liver (1.23±0.08 vs 1.43±0.05; p=0.013). Segments showing concomitant T 1 hyperintensity had lower mean ADC values than liver (1.30±0.05 vs 1.43±0.05; p50.023). The patients (8/10) with concomitant T 1 and DW-MRI segmental hyperintensity showed elevated ALT levels (p=0.030, Fisher's exact test). Conclusion: Concomitantly high T 1 weighted and DW-MRI signal in liver segments was associated with lower ADC values and abnormal liver function tests, which could reflect underlying cellular swelling and damage. © 2012 The British Institute of Radiology.
Cananzi F.C.M.,Royal Marsden |
Dalgleish A.,St George's, University of London |
Mudan S.,Royal Marsden
World Journal of Surgery | Year: 2014
Background: The aims of this study were to evaluate the role of surgery in the management of patients with intraabdominal metastases from melanoma and to investigate the neutrophil to lymphocyte ratio (NLR) as prognostic factor in this group of patients. Methods: Altogether, 44 patients who underwent surgery for Intraabdominal metastases from melanoma with curative, cytoreductive, or palliative intent were analyzed. Results: There were 77 intraabdominal organ resections performed during the 44 operations. R0 resection was achieved in 19 (43 %) cases. Factors associated with R0 resection were an absence of extra-abdominal metastases, low serum lactate dehydrogenase, involvement of fewer than three sites, and the presence of fewer than three metastatic lesions. The 1-, 3-, and 5-year overall survival rates were, respectively, 79, 66, and 44 % in the curative intent group; 36, 18, and 9 % in the cytoreduction group; and 21, 0 and 0 % in the palliation group (curative intent vs. cytoreduction vs. palliation p < 0.001). By Cox's multivariate analysis, the independent prognostic factors were time from excision of primary melanoma to the diagnosis of intraabdominal metastases, NLR, and residual disease after surgery. Conclusions: Our results confirm the usefulness of major surgical interventions as reported in previous studies. We reviewed recent evidence that immunologic phenomena may explain the unexpectedly good response rate in patients with advanced disease. The simple estimation of the NLR has been advocated as a prognostic marker for several cancers. We show that it is likewise useful in metastatic melanoma. We stress the need for developing additional immunologic markers. © 2013 Société Internationale de Chirurgie.
Cananzi F.C.M.,Royal Marsden |
Lorenzi B.,Royal Marsden |
Belgaumkar A.,Royal Marsden |
Benson C.,Sarcoma Unit |
And 2 more authors.
Langenbeck's Archives of Surgery | Year: 2014
Purpose: Gastrointestinal stromal tumours (GISTs) are the most common mesenchymal tumour of the gastrointestinal tract. The introduction of tyrosine kinase inhibitors (TKIs) has lead to increasing use of combination of medical and surgical therapy. The aim of this study was to look at outcomes from a series of surgically treated GISTs and determine prognostic factors in the context of multimodal therapy. Methods: We analysed 104 single surgeon's patients with GIST. End points of the study were disease-specific survival (DSS), disease-free survival (DFS) and post-operative complications. Results: Three- and 5-year DSS rates were 96.7 and 94.6 %. On univariate analysis, clear resection margins were predictive of DSS. Patients with R2 resection had a worse prognosis (3-year DSS rate of 83.3 %; 5-year DSS rate of 62.5 %) compared to patients with R0 (3-year DSS rate of 98 %; 5-year DSS rate of 98 %) or R1 resection (3-year DSS rate of 100 %; 5-year DSS rate of 100 %) (R0 vs R1 vs. R2 p = 0.001). Pre-operative factors associated with R2 resection were clinical metastatic disease (p < 0.001), non-gastric tumour site (p = 0.002) and large tumour diameter (p = 0.031). Three- and 5-year DFS rates were 65.5 and 59.8 %. Serosal perforation (p = 0.013) and mitotic rate (p = 0.05) were found to be independently predictive of increased DFS. The presence of serosal perforation was associated with tumour site (p = 0.018), mitotic rate (p = 0.035), tumour diameter (p < 0.001), growth pattern (p = 0.007) and age (p = 0.040). Conclusions: In the multidisciplinary management of GIST, serosal perforation may represent an additional predictor of recurrence along with mitotic rate. Complete macroscopic surgical resection is the most reliable prognostic factor, and an aggressive surgical approach should be advocated. © 2014 Springer-Verlag Berlin Heidelberg.
PubMed | Royal Marsden
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016
2509 Background: Phase I trials of novel molecularly targeted, non-cytotoxic agents, traditionally involve escalation to determine MTD, even though the need for this is uncertain. While the potential for response in phase I trials of classical cytotoxic agents has generally been considered to increase at higher dose levels, the same may not be true for molecularly targeted agents. For this drug class, in which cytostasis may be the main outcome, the clinical benefit rate (CBR)-defined as CR/PR/SD for at least 3 months by RECIST criteria-is a relevant measure of response.We analysed 252 consecutive patients (pts) who were treated in one of 29 phase I trials from Jan 05 to Jun 06. We excluded trials involving conventional chemotherapy, or trials involving molecularly targeted agents where the MTD was not reached. Three cohorts of pts were identified according to the percentage of the final trial MTD (0-33%, 34-65% and 66-100% of the MTD).145 pts included in 16 eligible trials were analysed. All pts had PD prior to entry. The median age was 57 yrs (range 20 - 86) and the male:female ratio was 2:1. Thirty-two (22%) pts received between 0-33% of the MTD, 24 pts (17%) between 34-65% and 89 pts (61%) between 66 and 100% of the MTD. CBR was 43% (63 pts) after the first tumour evaluation at 6-8 weeks, and has been maintained at 29% and 15% at three and six months, respectively. There were no significant differences in CBR at 3 and 6 months between the 3 cohorts ( table 1 ). The median duration of clinical benefit was 17 weeks (95%-CI= 13-22), and was not correlated with the MTD (p=0.9).This analysis showed that a substantial proportion of pts experienced clinical benefit from participating in a phase I trial of molecularly targeted agents, with no detriment to treatment at lower dose levels. These data may be helpful in the development of new phase I trial designs. [Table: see text] No significant financial relationships to disclose.