Publications by authors named "Jawaher Ansari"

25 Publications

  • Page 1 of 1

Prevalence and Risk Factors of Burnout Among Female Oncologists From the Middle East and North Africa.

Front Psychol 2022 22;13:845024. Epub 2022 Mar 22.

Cincinnati Cancer Advisors, Cincinnati, OH, United States.

Background: Burnout (BO) is a recognized challenge among the oncology workforce. It affects both genders with a higher frequency among women. This study examined the factors contributing to the development of burnout among female oncologists from the Middle East and North Africa (MENA).

Methods: An online cross-sectional survey was distributed to oncology professionals from different countries in the MENA region. The validated Maslach Burnout Inventory (MBI) of emotional exhaustion (EE), Depersonalization (DE), and Personal Achievement (PA) plus questions about demography/work-related factors and attitudes toward oncology were included. Data were analyzed to measure BO prevalence and related factors.

Results: Between 10 February and 15 March 2020, 545 responses were submitted by female oncologists. The responses pre-dated the COVID-19 pandemic emergence in the region. BO prevalence was 71% among female professionals. Women aged <44 years represented 85% of the cohort. Sixty-two percent were married, 52% with children and one-third practiced a hobby. Two-thirds worked in medical oncology, worked for <10 years and 35% worked in academia. The majority (73%) spent >25% on administrative work daily. Nearly half of the respondents (49%) expressed a recurring thought of quitting oncology and 70% had no burnout support or education. Inability to deliver optimal care was reported as distressing for career development in 82%. Factors significantly influencing the BO risk were identified. Marital status, having children, academia and years in practice did not impact the risk of BO among female oncologists from MENA.

Conclusion: Female oncologists from the Middle East and North Africa (MENA) were found to have a high prevalence of BO. In this cohort, the majority of women oncology workers were young and in their early to mid-career stages. Burnout was linked to being younger, practicing in North African nations, having a heavy administrative load, and having persistent thoughts of quitting. Practicing a hobby and engaging in oncology communication, on the other hand, reduced the chance of BO. Burnout support and education, specifically for oncology women, is required.
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http://dx.doi.org/10.3389/fpsyg.2022.845024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8980775PMC
March 2022

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review.

Gynecol Oncol Rep 2021 Nov 8;38:100878. Epub 2021 Oct 8.

Department of Radiation Oncology, Tawam Hospital, Al Ain, United Arab Emirates.

Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting. The efficacy of pembrolizumab in vaginal SCC has never been investigated in any clinical trial. There is established data to support the use of concurrent chemoradiotherapy in gynaecological cancers, however, the data for concurrent use of immunotherapy and radiotherapy is still lacking but is the subject of several clinical trials. We herein present the first reported case of chemotherapy refractory vaginal SCC with complete response to pembrolizumab and concurrent pelvic radiotherapy. We also present wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) as a rare but new immune related adverse event.
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http://dx.doi.org/10.1016/j.gore.2021.100878DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8651786PMC
November 2021

Concurrent use of nivolumab and radiotherapy for patients with metastatic non-small cell lung cancer and renal cell carcinoma with oligometastatic disease progression on nivolumab.

Mol Clin Oncol 2021 Oct 23;15(4):214. Epub 2021 Aug 23.

Department of Oncology, Royal Marsden Hospital, London SW3 6JJ, UK.

Checkpoint inhibitors (CPIs), such as nivolumab, have transformed the treatment paradigm for patients with metastatic non-small cell lung cancer (mNSCLC) and metastatic renal cell carcinoma (mRCC). The combination of CPIs and radiotherapy (RT) constitutes a multimodal treatment approach that may work synergistically and facilitate augmented systemic responses. The aim of the present retrospective study was to assess the efficacy and safety of continuation of nivolumab treatment with the addition of RT in patients with mNSCLC and mRCC who develop oligometastatic disease progression on single-agent nivolumab. All patients with mNSCLC and mRCC who received nivolumab at the Department of Oncology, Prince Sultan Military Medical City (Riyadh, Saudi Arabia) between November 2016 and April 2018 were identified. The records of patients who developed oligometastatic disease progression during nivolumab treatment and were subsequently treated with RT, with nivolumab continued beyond disease progression, were retrospectively reviewed. Details of RT, clinical outcomes and toxicity data were collected. Of the 96 patients who received nivolumab, 22 received multiple courses of RT. A total of 39 sites were irradiated: Bone (n=15), lung (n=9), brain (n=8), adrenal gland (n=2), renal bed (n=2), skin (n=1), ethmoid sinus (n=1) and scalp (n=1). Partial response and complete response were noted at 25 (64%) and 3 (8%) sites, respectively. Stable disease was noted at 6 sites (15%) and disease progression was noted at 5 sites (13%). The median time on nivolumab from the date of the first fraction of RT was 4.5 months (range, 1.5-29 months) for patients with mNSCLC and 5 months (range, 1-38.5 months) for patients with mRCC. No patients developed grade 3-4 toxicities. Grade 2 pneumonitis was noted in 3 patients receiving lung RT. The addition of RT appeared to initiate a response and prolong the duration of nivolumab treatment. Therefore, the combination of nivolumab and RT was found to be well tolerated, with response rates exceeding those in published studies of nivolumab monotherapy.
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http://dx.doi.org/10.3892/mco.2021.2376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408674PMC
October 2021

Burnout in oncology: Magnitude, risk factors and screening among professionals from Middle East and North Africa (BOMENA study).

Psychooncology 2021 05 2;30(5):736-746. Epub 2021 Feb 2.

Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background: Burnout (BO) among oncology professionals (OP) is increasingly being recognized. Early recognition and intervention can positively affect the quality of care and patient safety. This study investigated the prevalence, work and lifestyle factors affecting BO among OPs in the Middle East and North Africa (MENA).

Methods: An online survey was conducted among MENA OPs between 10 February and 15 March 2020, using the validated Maslach Burnout Inventory of emotional exhaustion (EE), depersonalization (DP) and personal accomplishment (PA), including questions regarding demography/work-related factors and attitudes towards oncology. Data were analysed to measure BO prevalence and risk factors and explore a screening question for BO.

Results: Of 1054 respondents, 1017 participants (64% medical oncologists, 77% aged less than 45 years, 55% female, 74% married, 67% with children and 40% practiced a hobby) were eligible. The BO prevalence was 68% with high levels of EE and DP (35% and 57% of participants, respectively) and low PA scores (49%). BO was significantly associated with age less than 44 years, administrative work greater than 25% per day and the thought of quitting oncology (TQ). Practising a hobby, enjoying oncology communication and appreciating oncology work-life balance were associated with a reduced BO score and prevalence. North African countries reported the highest BO prevalence. Lack of BO education/support was identified among 72% of participants and TQ-predicted burnout in 77%.

Conclusions: This is the largest BO study in MENA. The BO prevalence was high and several modifiable risk factors were identified, requiring urgent action. TQ is a simple and reliable screening tool for BO.
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http://dx.doi.org/10.1002/pon.5624DOI Listing
May 2021

Management guidelines for stage III non-small cell lung cancer.

Crit Rev Oncol Hematol 2021 Jan 7;157:103144. Epub 2020 Nov 7.

College of Medicine, Thoracic Surgery, Alfaisal University, Riyadh, Saudi Arabia.

Management of stage III non- small cell lung cancer (NSCLC) is very challenging due to being a group of widely heterogeneous diseases that require multidisciplinary approaches with timely and coordinated care. The standards of care had significant changes over the last couple of years because of the introduction of consolidation therapy with checkpoint inhibitor following concurrent chemo-radiotherapy and the evolving new role of tyrosine kinase inhibitors in the adjuvant setting. The manuscript presents evidence-based recommendations for the workup, staging, treatment and follow up of the various subtypes of stage III NSCLC. The guidelines were developed by experts in various fields of thoracic oncology and guidelines development. The guidelines consider the sequence of interventions and the role of each discipline in the management of the disease taking into account the recent development and included required resources to help physicians provide better care.
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http://dx.doi.org/10.1016/j.critrevonc.2020.103144DOI Listing
January 2021

The State of Cancer Care in the United Arab Emirates in 2020: Challenges and Recommendations, A report by the United Arab Emirates Oncology Task Force.

Gulf J Oncolog 2020 Jan;1(32):71-87

Mediclinic Al Noor Hospital, Abu Dhabi, United Arab Emirates.

With cancer being the third leading cause of mortality in the United Arab Emirates (UAE), there has been significant investment from the government and private health care providers to enhance the quality of cancer care in the UAE. The UAE is a developing country with solid economic resources that can be utilized to improve cancer care across the country. There is limited data regarding the incidence, survival, and potential risk factors for cancer in the UAE. The UAE Oncology Task Force was established in 2019 by cancer care providers from across the UAE under the auspices of Emirates Oncology Society. In this paper we summarize the history of cancer care in the UAE, report the national cancer incidence, and outline current challenges and opportunities to enhance and standardize cancer care. We provide recommendations for policymakers and the UAE Oncology community for the delivery of high-quality cancer care. These recommendations are aligned with the UAE government's vision to reduce cancer mortality and provide high quality healthcare for its citizens.
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January 2020

Rare Case of Intracardiac Renal Cell Carcinoma Metastasis with Response to Nivolumab: Case Report and Literature Review.

Case Rep Oncol 2018 Sep-Dec;11(3):861-870. Epub 2018 Dec 20.

Department of Oncology, Royal Marsden Hospital, London, United Kingdom.

Intracardiac metastases in the absence of inferior vena cava involvement is a rare occurrence in patients with metastatic renal cell carcinoma (mRCC). There is limited evidence regarding the efficacy and safety of standard treatment modalities for mRCC patients with intracardiac metastases. Presence of intracardiac metastases is known to indicate poor prognosis and may potentially increase risk of treatment-related complications. Recent advances in RCC management have integrated nivolumab, a programmed death-1 (PD-1) receptor inhibitor, as a preferred treatment option in the second-line setting after failure of prior anti-angiogenic therapy; or in combination with ipilimumab, an anti-Cytotoxic T-lymphocyte antigen-4 antibody as first-line therapy for intermediate to poor risk patients with mRCC. The efficacy and toxicity of nivolumab in patients with mRCC and intracardiac metastases has never been reported previously. We herein present the first reported case of mRCC with intracardiac metastasis and a resultant excellent response to nivolumab treatment and discuss the imaging techniques and treatment options for this rare presentation.
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http://dx.doi.org/10.1159/000495459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6341359PMC
December 2018

Efficacy of Nivolumab in a Patient with Metastatic Renal Cell Carcinoma and End-Stage Renal Disease on Dialysis: Case Report and Literature Review.

Case Reports Immunol 2018 13;2018:1623957. Epub 2018 Jun 13.

Department of Oncology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Treatment of patients with metastatic renal cell carcinoma (mRCC) and end-stage renal disease (ESRD) on dialysis poses a therapeutic challenge, particularly as this patient group was excluded from the pivotal clinical trials. In addition, there is uncertainty regarding drug dosing/pharmacokinetics, lack of safety and efficacy data, and potential for increased toxicity when using targeted therapy or immunotherapy for the management of patients with mRCC on dialysis. Nivolumab, an anti-programmed death-1 immune checkpoint inhibitor antibody, is indicated for the treatment of patients with mRCC who have received prior antiangiogenic therapy. Given the above-mentioned uncertainties, clinicians may be reluctant to use nivolumab for this patient population, leading to potential denial of life-prolonging medications. We report the case of a 72-year-old gentleman with mRCC and ESRD on dialysis who received second-line nivolumab therapy and achieved an excellent symptomatic and radiological response, remaining progression-free for over 22 months. In addition, we have reviewed the pharmacokinetic data and published retrospective case studies to review the management options for patients with mRCC and ESRD on dialysis.
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http://dx.doi.org/10.1155/2018/1623957DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6020478PMC
June 2018

Atypical diffuse bilateral cystic lung changes secondary to erlotinib treatment in a patient with metastatic non-small cell lung carcinoma: A case report and literature review.

Mol Clin Oncol 2018 Jul 4;9(1):92-95. Epub 2018 May 4.

Department of Oncology, Prince Sultan Military Medical City, Riyadh 11159, Saudi Arabia.

Erlotinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved in the first-line treatment of advanced non-small-cell lung cancer (NSCLC) patients with sensitizing epidermal growth factor receptor (EGFR) mutations. The response rate to erlotinib is ~60% and the incidence of erlotinib-induced interstitial lung disease (ILD) is ~1-4%. The Response Evaluation Criteria in Solid Tumours (RECIST) tool is commonly used to assess response to erlotinib; however, evaluation of response and subsequent progression in the presence of atypical cystic lung changes may be challenging. We herein present a rare case of diffuse cystic lung changes secondary to erlotinib treatment in a patient with EGFR mutation-positive metastatic NSCLC. Challenges in assessing atypical tumour response to erlotinib, pitfalls in using RECIST and differential diagnosis of TKI-related ILD are discussed in detail.
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http://dx.doi.org/10.3892/mco.2018.1620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030992PMC
July 2018

Intracranial meningioma as primary presentation for an undiagnosed collision metastatic breast cancer: Case report and literature review.

Mol Clin Oncol 2018 May 13;8(5):661-664. Epub 2018 Mar 13.

Department of Oncology, Prince Sultan Military Medical City, Riyadh, Riyadh 11159, Kingdom of Saudi Arabia.

Intracranial metastasis from breast cancer is a relatively common finding, however, the appearance of breast cancer metastasis in a meningioma is very rare. Several cases of tumor-to-tumor metastasis and collision tumors have been reported previously, with meningioma being implicated as the most common benign intracranial neoplasm to harbour the metastasis. Occasionally, the discovery of a tumor-to-meningioma metastasis may herald the diagnosis of an occult primary malignancy. Careful histopathological assessment of the resected meningioma specimen is pivotal to the management of these patients, as this will alter the treatment plan and prognosis considerably. Intracranial meningioma with collision breast cancer as primary presentation of an undiagnosed metastatic breast cancer is extremely rare. The current study presents a case of intracranial meningioma with collision breast cancer as a primary presentation, and reviews the available evidence for this unusual disease entity.
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http://dx.doi.org/10.3892/mco.2018.1589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920372PMC
May 2018

Saudi lung cancer management guidelines 2017.

Ann Thorac Med 2017 Oct-Dec;12(4):221-246

Department of Oncology, King Abdulaziz Medical City, Riyadh, Saudi Arabia.

Background: Lung cancer management is getting more complex due to the rapid advances in all aspects of diagnostic and therapeutic options. Developing guidelines is critical to help practitioners provide standard of care.

Methods: The Saudi Lung Cancer Guidelines Committee (SLCGC) multidisciplinary members from different specialties and from various regions and healthcare sectors of the country reviewed and updated all lung cancer guidelines with appropriate labeling of level of evidence. Supporting documents to help healthcare professionals were developed.

Results: Detailed lung cancer management guidelines were finalized with appropriate resources for systemic therapy and short reviews highlighting important issues. Stage based disease management recommendation were included. A summary explanation for complex topics were included in addition to tables of approved systemic therapy.

Conclusion: A multidisciplinary lung cancer guidelines was developed and will be disseminated across the country.
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http://dx.doi.org/10.4103/atm.ATM_92_17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5656941PMC
November 2017

Predictive and prognostic significance of CD8 tumor-infiltrating lymphocytes in patients with luminal B/HER 2 negative breast cancer treated with neoadjuvant chemotherapy.

Oncol Lett 2017 Jul 10;14(1):337-344. Epub 2017 May 10.

Division of Hematology/Oncology, Department of Medicine, King Khalid University Hospital/College of Medicine, King Saud University, Riyadh 11472 7805, Saudi Arabia.

The immunobiology of breast cancer (BC) subtypes, including luminal cancer, remains unclear. Cluster of differentiation (CD)8 tumor-infiltrating lymphocytes (TIL) are essential components of tumor-specific cellular adaptive immunity. However, only few studies have addressed the significance of cluster of differentiation 8(CD8) TIL in patients with luminal BC. The present study aimed to evaluate the predictive and prognostic significance of CD8 TIL in patients with luminal B/human epidermal growth factor receptor 2 (HER 2)-negative BC treated with anthracycline-based neoadjuvant chemotherapy (NC). A total of 31 patients who underwent breast-conserving surgery or mastectomy post-NC were enrolled. Immunostaining for CD8 TIL was performed using rabbit monoclonal antibodies against human CD8. Intra- and peritumoral CD8 TIL expression levels were classified into high and low, based on the median value of each. CD8 TIL expression data were demonstrated to be correlated with disease-free survival (DFS) and overall survival (OS), using Kaplan-Meier and Cox's proportional hazards regression tests. The results revealed that, among all clinicopathological characteristics, only pathological complete response (pCR) was significantly correlated with intratumoral CD8 TIL expression (P=0.016). A total of 9/16 patients (56%) with high intratumoral CD8 TIL expression achieved pCR, in contrast with 2 out of 15 patients (13.3%) with low expression (P=0.016). High expression of intratumoral CD8 TIL was significantly associated with OS (log-rank test, P=0.023). Multivariate Cox regression analysis revealed that intratumoral expression of CD8 TIL was an independent prognostic factor for OS [hazard ratio (HR)=2.82; 95% confidence interval (CI)=0.911-4.833, P=0.007], but not for DFS (HR=1.11; 95% CI=0.282-2.078; P=0.508). In conclusion, the results of the present study suggested that high intratumoral CD8 TIL expression was significantly predictive of pCR post-NC, and represented an independent prognostic factor for improved OS. In contrast, low intratumoral CD8 TIL expression was a strong predictor of lack of pCR to NC, as well as an independent prognostic factor for poor OS. Assessment of the immune response in conjunction with the usual parameters may aid in the further stratification of patients with luminal B/HER 2-negative BC regarding the prediction of pCR post-NC and overall prognosis.
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http://dx.doi.org/10.3892/ol.2017.6144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5494820PMC
July 2017

Gene expression profiling in bladder cancer identifies potential therapeutic targets.

Int J Oncol 2017 Apr 2;50(4):1147-1159. Epub 2017 Mar 2.

School of Cancer Sciences, University of Birmingham, Birmingham B15 2TT, UK.

Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation.
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http://dx.doi.org/10.3892/ijo.2017.3893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5363876PMC
April 2017

VICTOR: Vinflunine in advanced metastatic transitional cell carcinoma of the urothelium: A retrospective analysis of the use of vinflunine in multi-centre real life setting as second line chemotherapy through Free of Charge Programme for patients in the UK and Ireland.

Int J Oncol 2017 Mar 13;50(3):768-772. Epub 2017 Jan 13.

University of Liverpool, Liverpool L69 3GA, UK.

There is no standard of care in the UK or Ireland for second-line chemotherapy for patients with advanced transitional cell carcinoma (TCCU). Vinflunine is approved for TCCU patients who have failed a platinum-based regimen, and is standard of care in Europe but is not routinely available in the UK. Data were collected retrospectively on patients who received vinfluine as a second-line treatment. The aims were to document the toxicity and efficacy in a real life setting. Data were collected on 49 patients from 9 sites across the UK and Ireland [median age, 64 (IQR, 57-70) years, 33 males]. All patients had advanced metastatic TCCU. Thirteen patients had bone or liver metastases, 4 patients had PS 2 and 11 patients had HB <10. Median vinflunine administration was 3.5 cycles (range 1-18). Most common grade 3-4 toxicities were constipation (4 patients) and fatigue (3 patients). Partial response rate was 29% (14 PR, 11 SD, 19 PD, 4 NE, 1 not available). Median OS was 9.1 (6.0, 12.7) months. Results are consistent with real life data from Europe. Toxicity is further reduced with prophylactic laxative and oral antibiotics. Vinflunine is an efficient and tolerable second line treatment in advanced TCCU.
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http://dx.doi.org/10.3892/ijo.2017.3847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5358710PMC
March 2017

Triple Negative Breast Cancer: A Tale of Two Decades.

Anticancer Agents Med Chem 2017 ;17(4):491-499

Oncology Center, King Khalid University Hospital, King Saud University, Saudi Arabia.

Triple negative breast cancer (TNBC) is a heterogeneous disease entity constituting about 15% of breast cancer cases worldwide. TNBC is associated with poor prognosis and lack of sustained response to conventional chemotherapeutic agents. Tumoral heterogeneity and the presence of several subtypes of TNBC such as Basal like (BL)-1, BL-2, immune-modulatory, luminal androgen receptor, mesenchymal, and mesenchymal/stem like subtype and claudin low subtype, may explain some of the difficulties faced in managing this challenging disease subgroups. Although no approved targeted therapy is available for TNBCs, molecular-profiling efforts have revealed promising molecular targets such as the vascular endothelial growth factor (VEGF), epidermal growth factor receptor (EGFR), polyadenosine ribose polymerase inhibitors (PARPi) and DNA repair pathway, androgen pathway, and NOTCH pathway. TNBC is subject to intense research activities aiming at dissecting potential pathways, identifying potential molecular signatures and biomarkers in order to properly develop new targeted biologic modifiers. Despite this, there is a lack of approved predictive and prognostic biomarkers, and keeping in view the complexity of TNBC biology, research should be targeted towards identifying multi-factorial signatures rather than single markers. This review aims to summarize the current evidence, ongoing research and discuss future strategies for the treatment of patients with TNBC. In addition we have reviewed the recent advances in detecting predictive and prognostic biomarkers and identifying surrogate markers for early identification of potential responders to the new therapies.
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http://dx.doi.org/10.2174/1871520616666160725112335DOI Listing
August 2017

Evolution of the treatment paradigm for patients with metastatic castration-resistant prostate cancer.

Adv Ther 2013 Dec 26;30(12):1041-66. Epub 2013 Nov 26.

Clatterbridge Cancer Centre NHS Foundation Trust, Clatterbridge Road, Bebington, Wirral, Merseyside, CH63 4JY, UK,

As recently as 2004, treatment options for men with metastatic castration-resistant prostate cancer (mCRPC) were limited, with docetaxel the only approved agent conferring a survival benefit. The therapeutic landscape is now very different, with several agents demonstrating prolonged survival since 2010. New agents for the treatment of mCRPC include sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide and radium-223. All are now approved for use in this patient group, although the specific licensing terms vary between agents. In addition, denosumab may have utility in patients with bone metastases. A number of novel agents are also in development with promising initial results. However, because these treatment options have proliferated rapidly, there is currently a paucity of clinical evidence regarding their optimal sequencing. Selection of an appropriate treatment option should take into consideration disease characteristics, drug availability and patient choice. In summary, we discuss several new treatment options available for mCRPC and their integration into the current treatment paradigm.
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http://dx.doi.org/10.1007/s12325-013-0070-zDOI Listing
December 2013

Variability in prostate and seminal vesicle delineations defined on magnetic resonance images, a multi-observer, -center and -sequence study.

Radiat Oncol 2013 May 24;8:126. Epub 2013 May 24.

Background: The use of magnetic resonance (MR) imaging as a part of preparation for radiotherapy is increasing. For delineation of the prostate several publications have shown decreased delineation variability using MR compared to computed tomography (CT). The purpose of the present work was to investigate the intra- and inter-physician delineation variability for prostate and seminal vesicles, and to investigate the influence of different MR sequence settings used clinically at the five centers participating in the study.

Methods: MR series from five centers, each providing five patients, were used. Two physicians from each center delineated the prostate and the seminal vesicles on each of the 25 image sets. The variability between the delineations was analyzed with respect to overall, intra- and inter-physician variability, and dependence between variability and origin of the MR images, i.e. the MR sequence used to acquire the data.

Results: The intra-physician variability in different directions was between 1.3 - 1.9 mm and 3 - 4 mm for the prostate and seminal vesicles respectively (1 std). The inter-physician variability for different directions were between 0.7 - 1.7 mm and approximately equal for the prostate and seminal vesicles. Large differences in variability were observed for individual patients, and also for individual imaging sequences used at the different centers. There was however no indication of decreased variability with higher field strength.

Conclusion: The overall delineation variability is larger for the seminal vesicles compared to the prostate, due to a larger intra-physician variability. The imaging sequence appears to have a large influence on the variability, even for different variants of the T2-weighted spin-echo based sequences, which were used by all centers in the study.
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http://dx.doi.org/10.1186/1748-717X-8-126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3680182PMC
May 2013

Efficacy of temsirolimus in metastatic chromophobe renal cell carcinoma.

BMC Urol 2013 May 21;13:26. Epub 2013 May 21.

Beatson West of Scotland Cancer Centre, 1053, Great Western Road, Glasgow G12 0YN, UK.

Background: Renal cell carcinoma (RCC) is a histopathologically and molecularly heterogeneous disease with the chromophobe subtype (chRCC) accounting for approximately 5% of all cases. The median overall survival of advanced RCC has improved significantly since the advent of tyrosine kinase inhibitors and mammalian target of rapamycin (mTOR) inhibitors. However, high-quality evidence for the use of new generation tyrosine kinase inhibitors in patients with advanced chRCC is lacking. Few published case reports have highlighted the use of temsirolimus in chRCC.

Case Presentation: Here, we report the case of a 36-year-old Caucasian woman with metastatic chRCC with predominantly skeletal metastases who was refractory to sunitinib who demonstrated a durable clinical response to temsirolimus lasting 20 months. We review the available evidence pertaining to the use of new generation molecularly targeted agents, in particular mTOR inhibitors in chRCC and discuss their emerging role in the management of this disease which would aid the oncologists faced with the challenge of treating this rare type of RCC.

Conclusion: Conducting randomised clinical trials in this rarer sub-group of patients would be challenging and our case report and the evidence reviewed would guide the physicians to make informed decision regarding the management of these patients.
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http://dx.doi.org/10.1186/1471-2490-13-26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3679738PMC
May 2013

Critical appraisal of axitinib in the treatment of advanced renal cell carcinoma.

Biologics 2013 28;7:39-46. Epub 2013 Feb 28.

Beatson West of Scotland Cancer Centre, Glasgow, UK.

A growing understanding of the biology of renal cell carcinoma (RCC) has led to the development and US Food and Drug Administration approval of seven new molecular targeted agents over the past 7 years. Axitinib is a potent, selective, second-generation inhibitor of vascular endothelial growth factor receptors and the latest to join the armamentarium of drugs available for the treatment of metastatic RCC. Despite recent advances in the development of molecular targeted agents for metastatic RCC, the ideal sequencing of these agents remains unclear.
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http://dx.doi.org/10.2147/BTT.S25862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3588609PMC
March 2013

Role of second-line systemic treatment post-docetaxel in metastatic castrate resistant prostate cancer- current strategies and future directions.

Anticancer Agents Med Chem 2011 Mar;11(3):296-306

Consultant in Clinical Oncology, Beatson West of Scotland Cancer Centre, Glasgow, UK.

Treatment of metastatic castrate resistant prostate cancer (mCRPC) after progression on docetaxel chemotherapy is a challenging clinical scenario with limited availability of treatment options. Re-treatment with docetaxel, either as monotherapy or in combination with other cytotoxics or targeted agents has shown durable responses. However, most docetaxel re-treatment studies have been either retrospective or early phase non-randomised studies which have not formally assessed Quality of life or survival gain with re-treatment. Despite limited evidence for efficacy of mitoxantrone in the second-line, it continues to remain widely used, largely due to lack of available suitable alternatives. Cabazitaxel in combination with prednisolone is the only chemotherapy to have shown a significant survival benefit and receive approval by the U.S. Food and Drug Administration for patients with mCRPC previously treated with a docetaxel-based regimen. Abiraterone acetate has recently demonstrated a significant improvement in survival when compared to placebo in patients with docetaxel-treated mCRPC. This review aims to summarize the current evidence and discuss future strategies for treatment of mCRPC patients following failure of docetaxel chemotherapy.
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http://dx.doi.org/10.2174/187152011795347496DOI Listing
March 2011

Sunitinib in patients with metastatic renal cell carcinoma: Birmingham experience.

Oncol Rep 2010 Aug;24(2):507-10

University Hospital Birmingham NHS Trust, University of Birmingham, Edgbaston, Birmingham B15 2TH, UK.

Sunitinib is a novel, multi-targeted receptor tyrosine kinase inhibitor, which has demonstrated evidence of improved survival when compared to interferon (IFN)-alpha in patients with metastatic renal cell carcinoma (RCC). Recently published National Institute for Health and Clinical Excellence guidance recommends sunitinib as a first-line treatment option for patients with advanced and/or metastatic RCC. We assessed the efficacy and toxicity of sunitinib in an unselected group of patients with metastatic RCC, and compared outcomes in clinical practice with published clinical trial results. Between June 2006 and March 2008, 56 patients with metastatic RCC gave informed consent for commencement of sunitinib treatment at our institution. Median age was 61 years (range: 33-78); 68% had clear-cell histology; 86% had undergone prior nephrectomy; and 50% had progressed on IFN-alpha prior to commencement of sunitinib. Sunitinib was administered orally at a dose of 50 mg once daily, in 6-week cycles consisting of 4 weeks of treatment followed by a 2-week break. All patients were evaluable for toxicity, and 49 for response. The mean dose of sunitinib was 38.15 mg/cycle (range: 25-50); and 402 cycles of sunitinib were delivered. Partial response and stable disease were observed in 41 and 37% of patients, respectively. Median progression-free survival and overall survival were 12.2 and 18.2 months, respectively. The most common adverse events (all grades) were mucositis (79%) and fatigue (75%). Grade 3/4 neutropenia was observed in 13%, and treatment-related hypothyroidism in 20%, of patients. Dose-reduction was necessary in 75% of patients, and 32% needed hospital admission for treatment-related toxicities. The results from this study confirm the efficacy of sunitinib in the first- and second-line treatment of an unselected group of patients with metastatic RCC. Compared to published data, there was a higher incidence of treatment-related toxicities and a greater necessity for dose-reductions. Despite the increase in toxicity, these results are encouraging and imply that the clinical trial results seen with sunitinib can be translated into routine clinical practice.
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http://dx.doi.org/10.3892/or_00000886DOI Listing
August 2010

Fatal Clostridium difficile infection associated with vinorelbine chemotherapy: case report and literature review.

J Infect Chemother 2010 Jun 3;16(3):210-2. Epub 2010 Mar 3.

Beatson West of Scotland Cancer Centre, Glasgow, UK.

Differentiating between chemotherapy-related diarrhoea and Clostridium difficile-associated diarrhoea (CDAD) can be extremely difficult. There is increasing evidence that CDAD can be seen in patients on chemotherapy without prior antibiotic usage. We report the first case of CDAD secondary to vinorelbine chemotherapy and review the literature.
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http://dx.doi.org/10.1007/s10156-010-0041-0DOI Listing
June 2010

Neoadjuvant sunitinib facilitates nephron-sparing surgery and avoids long-term dialysis in a patient with metachronous contralateral renal cell carcinoma.

Clin Genitourin Cancer 2009 Aug;7(2):E39-41

University Hospital Birmingham, NHS Trust, UK.

Bilateral Renal Cell Carcinoma (RCC) is an uncommon clinical entity, affecting 3%-6% of patients with localized RCC. Sunitinib has proven efficacy in the management of metastatic RCC (mRCC), however, there is very limited evidence of primary tumor response. With the changing treatment paradigm, the role of sunitinib should be extended to the neoadjuvant setting, to downstage locally advanced primary renal tumors, to facilitate nephron-sparing surgery (NSS), and to select responding patients with mRCC for continuation of treatment after cytoreductive nephrectomy. The role of sunitinib in downstaging primary renal tumors to facilitate curative NSS has not been previously reported. We report the case of recurrent renal tumors in a solitary kidney, where neoadjuvant sunitinib downstaged the tumors enough to allow NSS.
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http://dx.doi.org/10.3816/CGC.2009.n.021DOI Listing
August 2009

Sorafenib induces therapeutic response in a patient with metastatic collecting duct carcinoma of kidney.

Onkologie 2009 Feb 19;32(1-2):44-6. Epub 2009 Jan 19.

University Hospital Birmingham NHS Trust, Queen Elizabeth Hospital, Metchley Drive, Birmingham, UK.

Background: Collecting duct carcinoma (CDC) is a rare and aggressive variant of renal cell carcinoma (RCC), which has poor response to cytokine therapy and chemotherapy. Introduction of tyrosine kinase inhibitors (TKIs), in particular sorafenib and sunitinib, is changing the treatment paradigm for management of RCC. However, patients with CDC have been excluded from the majority of randomised trials involving the use of TKIs.

Case Report: Our patient with metastatic CDC was treated with sorafenib, and demonstrated an excellent response, both clinically and radiologically. She continues on sorafenib treatment with minimal toxicity, and has demonstrated a progression-free survival exceeding 13 months.

Conclusions: This is the first reported case of a patient with CDC responding to sorafenib treatment. Therefore, the role of sorafenib in the management of metastatic CDC needs prospective evaluation.
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http://dx.doi.org/10.1159/000183736DOI Listing
February 2009

Docetaxel chemotherapy for metastatic hormone refractory prostate cancer as first-line palliative chemotherapy and subsequent re-treatment: Birmingham experience.

Oncol Rep 2008 Oct;20(4):891-6

University Hospital Birmingham NHS Trust, Metchley Drive, Birmingham, UK.

Three-weekly docetaxel chemotherapy with prednisolone is now considered standard of care for patients with metastatic hormone refractory prostate cancer (MHRPC). This study reports the efficacy and toxicity of first-line docetaxel chemotherapy followed subsequently by re-treatment on biochemical disease progression (BDP). Forty-two patients with MHRPC were treated with three-weekly docetaxel chemotherapy 75 mg/m(2) and 10 mg of prednisolone daily. Median age 73 years (range 58-87) and median initial PSA 182 ng/ml (range 19.9-1500). Of these patients, 10 were re-treated with the same regimen (second-line chemotherapy) on BDP. A further 3 out of these 10 patients received 2nd re-treatment (third-line chemotherapy) with docetaxel chemotherapy on BDP. Fifty-four percent of patients responded to first-line docetaxel chemotherapy and all re-treated patients responded again with a PSA reduction >50%. Median treatment-free interval prior to second and third-line chemotherapy was 24 and 26 weeks, respectively. Grade 3 or 4 neutropenia occurred in 2.5, 7 and 12% of the total number of cycles in patients receiving first-, second- and third-line docetaxel chemotherapy, respectively. Median survival was 13 months (range 3-35) and one-year overall survival 52%. This is the first report of three-weekly docetaxel chemotherapy re-treatment in patients with MHRPC and demonstrates that patients who initially respond to docetaxel chemotherapy maintain their sensitivity to subsequent re-treatment without a significant rise in haematological toxicity.
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October 2008
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