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1.
BMC Cancer ; 21(1): 593, 2021 May 24.
Article in English | MEDLINE | ID: mdl-34030643

ABSTRACT

BACKGROUND: ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC). METHODS: Patients with UC were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks. RESULTS: Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration. CONCLUSIONS: Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer. TRIAL REGISTRATION: This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017-004166-10).


Subject(s)
Carcinoma, Transitional Cell/drug therapy , Indoles/administration & dosage , Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Administration, Oral , Aged , BRCA1 Protein/genetics , BRCA2 Protein/genetics , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/mortality , Carcinoma, Transitional Cell/secondary , DNA Repair , Female , Follow-Up Studies , Humans , Indoles/adverse effects , Loss of Heterozygosity , Male , Middle Aged , Poly(ADP-ribose) Polymerase Inhibitors/adverse effects , Progression-Free Survival , Response Evaluation Criteria in Solid Tumors , Urinary Bladder/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/mortality , Urinary Bladder Neoplasms/pathology
2.
Urol Oncol ; 36(7): 345-346, 2018 07.
Article in English | MEDLINE | ID: mdl-29859727

ABSTRACT

PURPOSE: Platinum-based chemotherapy remains the standard treatment for advanced urothelial carcinoma by inducing DNA damage. We hypothesize that somatic alterations in DNA damage response and repair (DDR) genes are associated with improved sensitivity to platinum-based chemotherapy. EXPERIMENTAL DESIGN: Patients with diagnosis of locally advanced and metastatic urothelial carcinoma treated with platinum-based chemotherapy who had exon sequencing with the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) assay were identified. Patients were dichotomized based on the presence/absence of alterations in a panel of 34 DDR genes. DDR alteration status was correlated with clinical outcomes and disease features. RESULTS: One hundred patients were identified, of which 47 harbored alterations in DDR genes. Patients with DDR alterations had improved progression-free survival (9.3 vs. 6.0 months, log-rank P = 0.007) and overall survival (23.7 vs. 13.0 months, log-rank P = 0.006). DDR alterations were also associated with higher number mutations and copy-number alterations. A trend toward positive correlation between DDR status and nodal metastases and inverse correlation with visceral metastases were observed. Different DDR pathways also suggested variable effect on clinical outcomes. CONCLUSIONS: Somatic DDR alteration is associated with improved clinical outcomes in platinum-treated patients with advanced urothelial carcinoma. Once validated, it can improve patient selection for clinical practice and future study enrollment.


Subject(s)
Carcinoma, Transitional Cell , Platinum , DNA Damage , Humans , Mutation , Urologic Neoplasms
3.
J Neurooncol ; 114(1): 149-54, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23780645

ABSTRACT

Neutrophil-lymphocyte ratio (NLR) is a marker of systemic inflammatory response and its elevation has recently been shown to be a poor prognostic factor in many malignancies including colon, prostate and bladder cancer. The primary aim of this study was to assess the prognostic impact of NLR in a clinically annotated cohort of patients with glioblastoma multiforme (GBM). We hypothesised that elevated NLR would be associated with worse prognosis. Between 2004 and 2009, 137 patients had surgery for GBM and were assessed for consideration of adjuvant therapy at our institution. Of these, 84 patients with an evaluable pre-corticosteroid full blood count result were identified and included in the final analysis. Median overall survival was 9.3 months (range 0.7-82.1). On univariate analysis, age >65 years, gender, ECOG performance status ≥2, frontal tumour, extent of surgical resection, completion of adjuvant chemoradiation protocol and NLR > 4 were significantly correlated with overall survival. Patients with NLR > 4, had a worse median overall survival at 7.5 months versus 11.2 months in patients with NLR ≤ 4 (hazard ratio 1.6, 95 % CI 1.00-2.52, p = 0.048). On multivariate analysis NLR > 4 remained an independent prognostic indicator for poor outcome. These data are an important reminder of the potential relevance of host immunity in GBM. In our cohort, NLR > 4 conferred a worse prognosis independent of other well established prognostic factors. If validated in other cohorts NLR may prove to be a useful addition in predicting prognosis in GBM patients. The demonstration that host immunity plays a role in GBM biology suggests that investigation of emerging therapies which modulate host immune response are warranted in this disease.


Subject(s)
Brain Neoplasms/mortality , Brain Neoplasms/pathology , Glioblastoma/mortality , Glioblastoma/pathology , Lymphocytes/pathology , Neutrophils/pathology , Adolescent , Adult , Age Factors , Aged , Blood Cell Count , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Retrospective Studies , Statistics, Nonparametric , Young Adult
4.
Ir Med J ; 106(9): 262, 264-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24416846

ABSTRACT

UNLABELLED: Irish breast cancer survivor's needs have not been studied. Physical, psychological, social and spiritual concerns were investigated. Patient satisfaction with hospital discharge, GP follow-up, and the benefit of a discharge pack was investigated. A cohort of patients from the South East Cancer Centre was identified. INCLUSION CRITERIA: localized breast cancer, completion of adjuvant therapy, GP-led follow-up in the last 5 years. An anonymous questionnaire was developed, and ethical approval obtained. Subgroup analyses for age and time since diagnosis and discharge were completed. 80 patients were identified. 44 patients (55%) completed the questionnaire, 5 (6%) were excluded. Commonest concerns included: fatigue (51%), fear of recurrence (69%) and second cancers concerns (69%) 23 (59%) and 25 patients (64%) were satisfied with discharge and GP follow-up respectively. 27 patients (67%) reported benefit from a discharge pack. Irish breast cancer survivors had concerns, and were satisfied with GP follow-up.


Subject(s)
Breast Neoplasms/psychology , Health Services Needs and Demand , Survivors/psychology , Adult , Aged , Breast Neoplasms/mortality , Breast Neoplasms/therapy , Female , Humans , Ireland/epidemiology , Middle Aged , Patient Satisfaction , Surveys and Questionnaires
5.
J Phys Chem A ; 114(12): 4173-80, 2010 Apr 01.
Article in English | MEDLINE | ID: mdl-20218701

ABSTRACT

The conversions of NiAs-type structures of transition metal chalcogenides (FeS and CoSe) to pyrite-type structures of dichalcogenides (FeS(2) and CoSe(2), respectively) under irradiation by HeNe laser (wavelength, 632.8 nm; intensity, 6 x 10(4) W/cm(2)) have been investigated using Raman spectroscopy. The laser-induced conversions give rise to Raman peaks corresponding to vibrations of S-S or Se-Se bonds of respective pyrite structures. The results are of interest for the characterization and fabrication of pyrite-like structures necessary for applications as oxygen reduction reaction catalysts. Material modifications at the micrometer and submicrometer levels are attainable. The structural conversions are accompanied by self-polymerization of excess chalcogen. Extended laser irradiation (>500 s) in air induces the substitution of chalcogen (S or Se) by oxygen in the chalcogenide materials and the subsequent formation of transition metal (Fe or Co) oxides. Excess chalcogen appears to prevent further oxidation. The article also presents conditions necessary to avoid laser-induced structural changes and oxidation of metal chalcogenide materials during Raman measurements.

6.
IEEE Trans Biomed Eng ; 48(10): 1125-33, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11585036

ABSTRACT

Computer-Assisted transurethral laser resection of the prostate (CALRP) is a treatment modality that was designed and developed based on an integrated system of computer, robotics and laser technology in association with a minimally invasive surgery known as laser transurethral resection of the prostate (LRP). CALRP possesses complementary capabilities that could remedy many of the problems faced by surgeons in conventional LRP by delivering a treatment with repeatability and reliability. The work deals primarily in determining the feasibility study of the computer-assisted lasing motion plan (planned motion sequence controlled by a program) for LRP. A theoretical motion plan that analyzes numerically the lasing motion of the fiber was designed by calculating the profile removal rate and in vitro experiments conducted on human cadaveric prostate to verify and validate the designed motion plan. The novel motion plan, which was executed experimentally using the LaserTrode lightguide, accomplished the objective of resecting the enlarged prostate with the aid of computer and robotics technology.


Subject(s)
Laser Therapy/instrumentation , Prostate/surgery , Robotics , Therapy, Computer-Assisted/instrumentation , Transurethral Resection of Prostate/instrumentation , Cadaver , Computer Simulation , Equipment Design , Humans , Male , Phantoms, Imaging
7.
J Biomed Opt ; 6(2): 244-51, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11375736

ABSTRACT

A longer operating time and steeper learning curve in mastering the techniques for transurethral laser resection of the prostate are the main problems faced by surgeons in addition to the existing ones in standard transurethral resection of the prostate (TURP). However, these disadvantages can be alleviated with the introduction of a treatment procedure designed and developed based on an integrated system of computer, robotics and laser technology. In vitro experiments were carried out to determine variables affecting the vaporization and coagulation lesions, in order to study the effectiveness and feasibility of robotics for this procedure. Human cadaveric prostates and fresh tauted chicken breast tissues were irradiated with different parameters using the LaserTrode lightguide in contact with the tissue. The effects of irrigant flow rate, fiber/tissue angle of inclination, number of passes, direction, speed and power of lase on the volume of tissue vaporized and coagulated, were assessed. The final phase of the experiments includes executing the robotic motion plan for the laser resection procedure on the human cadaveric prostate tissue embedded in an anatomically alike prostate phantom. It was concluded from our study that power and speed of lase are the most significant parameters influencing the volume of the vaporized and coagulated lesion. Comparison of removal rate using the new treatment procedure of robotic laser resection of the prostate with TURP and HoLRP evinced equivalent results.


Subject(s)
Laser Therapy/instrumentation , Laser Therapy/methods , Lighting/instrumentation , Prostate/surgery , Robotics , Animals , Cadaver , Chickens , Equipment Design , Feasibility Studies , Female , Humans , Male , Muscle, Skeletal/pathology , Muscle, Skeletal/surgery , Time Factors
9.
Med Biol Eng Comput ; 36(6): 768-71, 1998 Nov.
Article in English | MEDLINE | ID: mdl-10367470

ABSTRACT

In a computerised ultrasound image guidance for automated prostatectomy system, it is necessary to identify a smooth, continuous contour for the prostate (boundary) from the ultrasound image. The radial bas-relief (RBR) method, which has been reported previously, can extract a skeletonised image from an ultrasound image automatically. After this process the prostate boundary is clearly revealed. However, analysis of the image is far from complete, as there are many spurious branches that create too much ambiguity for the system to define the actual boundary. There are also sections missing from the prostate boundary. Therefore further post-processing is required to describe and define the prostate boundary. In the paper, the harmonics method is used to describe the prostate boundary. The harmonics method uses Fourier information for noise removal and encodes a smooth boundary. The results of using the harmonics method after application of the RBR method on ultrasound images are presented. Factors that affect the performance are also highlighted and discussed.


Subject(s)
Image Processing, Computer-Assisted/methods , Prostate/diagnostic imaging , Ultrasonography, Interventional/methods , Fourier Analysis , Humans , Male , Prostatectomy/methods
10.
Med Biol Eng Comput ; 35(5): 445-54, 1997 Sep.
Article in English | MEDLINE | ID: mdl-9374046

ABSTRACT

A new method is presented for automatic prostate boundary detection in ultrasound images taken transurethrally or transrectally. This is one of the stages in the implementation of a robotic procedure for prostate surgery performed by a robot known as the robot for urology (UROBOT). Unlike most edge detection methods, which detect object edges by means of either a spatial filter (such as Sobel, Laplacian or something of that nature) or a texture descriptor (local signal-to-noise ratio, joint probability density function etc.), this new approach employs a technique called radial bas-relief (RBR) to outline the prostate boundary area automatically. The results show that the RBR method works well in the detection of the prostate boundary in ultrasound images. It can also be useful for boundary detection problems in medical images where the object boundary is hard to detect using traditional edge detection algorithms, such as ultrasound of the uterus and kidney.


Subject(s)
Image Enhancement/methods , Image Interpretation, Computer-Assisted , Prostate/diagnostic imaging , Prostatic Hyperplasia/diagnostic imaging , Humans , Male , Prostatectomy , Prostatic Hyperplasia/surgery , Robotics , Ultrasonography
11.
Nurs Times ; 73(1): 32-3, 1977 Jan 06.
Article in English | MEDLINE | ID: mdl-840655
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