Update on the Treatment of Metastatic Urothelial Carcinoma.

Platinum-based combination chemotherapy has been the standard of care in the first-line treatment of metastatic urothelial carcinoma (mUC). Treatment of metastatic disease following progression on platinum-based regimens has evolved significantly in the last few years. Clinical trials are currently ongoing to determine how best to use and sequence these treatments. In this minireview, we will review current first-line treatment options in both cisplatin fit and cisplatin unfit patients and advances in first- and second-line treatments including chemotherapy and immunotherapy. This review reports key findings from the clinical trials especially highlighting the importance of PD-1 and PD-L1 inhibitors in the treatment of bladder/urothelial carcinomas.

Thymidylate Synthase (TYMS) and Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms Associated With Severe Capecitabine Toxicity: The First Case From Saudi Arabia.

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of fluoropyrimidine chemotherapy. Deficiencies in this enzyme level typically predispose patients to fluoropyrimidine toxicities, and they are often linked to DPYD gene polymorphisms. Other gene polymorphisms such as thymidylate synthase (TYMS) and methylenetetrahydrofolate reductase (MTHFR) may induce similar toxicities. We report a patient with resected stage III colon cancer presenting with severe toxicity to adjuvant capecitabine, a prodrug of 5-fluorouracil (5-FU). Her DPYD gene sequencing was normal. However, the patient was heterozygous for c.1298A>C (p.E429A) in the methylenetetrahydrofolate reductase (MTHFR) gene and c.*450_*455del in the thymidylate synthase (TYMS) gene. The capecitabine dose was reduced in subsequent treatments and then titrated up gradually with no major side effects reported.

Navigated Transcranial Magnetic Stimulation (nTMS) based Preoperative Planning for Brain Tumor Treatment.

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique for analyzing the central and peripheral nervous system. TMS could be a powerful therapeutic technique for neurological disorders. TMS has also shown potential in treating various neurophysiological complications, such as depression, anxiety, and obsessive-compulsive disorders, without pain and analgesics. Despite advancements in diagnosis and treatment, there has been an increase in the prevalence of brain cancer globally. For surgical planning, mapping brain tumors has proven challenging, particularly those localized in expressive regions. Preoperative brain tumor mapping may lower the possibility of postoperative morbidity in surrounding areas. A navigated TMS (nTMS) uses magnetic resonance imaging (MRI) to enable precise mapping during navigated brain stimulation. The resulting magnetic impulses can be precisely applied to the target spot in the cortical region by employing nTMS. This review focuses on nTMS for preoperative planning for brain cancer. This study reviews several studies on TMS and its subtypes in treating cancer and surgical planning. nTMS gives wider and improved dimensions of preoperative planning of the motor-eloquent areas in brain tumor patients. nTMS also predicts postoperative neurological deficits, which might be helpful in counseling patients. nTMS have the potential for finding possible abnormalities in the motor cortex areas.

Current Status of CRISPR/Cas9 Application in Clinical Cancer Research: Opportunities and Challenges.

Cancer is considered by not only multiple genetic but also epigenetic amendments that drive malignant cell propagation and consult chemo-resistance. The ability to correct or ablate such mutations holds enormous promise for battling cancer. Recently, because of its great efficiency and feasibility, the CRISPR-Cas9 advanced genome editing technique has been extensively considered for therapeutic investigations of cancers. Several studies have used the CRISPR-Cas9 technique for editing cancer cell genomic DNA in cells and animal cancer models and have shown therapeutic potential in intensifying anti-cancer protocols. Moreover, CRISPR-Cas9 may be used to correct oncogenic mutations, discover anticancer drugs, and engineer immune cells and oncolytic viruses for immunotherapeutic treatment of cancer. We herein discuss the challenges and opportunities for translating therapeutic methods with CRISPR-Cas9 for clinical use and suggest potential directions of the CRISPR-Cas9 system for future cancer therapy.

Malignant anaplastic meningioma in neurofibromatosis type 1 patient: a rare case report.

Background: Meningiomas are usually associated with neurofibromatosis type 2 (NF-2), while gliomas are usually associated with neurofibromatosis type 1 (NF-1). NF-1 is an autosomal dominant genetic disorder associated with skin manifestations, bone conditions, and different types of benign and malignant tumors. Grade 3 anaplastic meningiomas are rare tumors with a poor prognosis. Systemic treatments in grade 3 meningiomas are experimental, with some reports suggestive of minimal clinical benefits. They are used occasionally for recurrent cases with no surgical or radiotherapy roles. In our case, we will focus the discussion on grade 3 anaplastic meningioma in a patient with NF-1, using chemotherapy for this aggressive, recurrent tumor. To our knowledge, this is the first case of NF-1 associated with malignant anaplastic meningioma in English literature. Case Description: In this case report, we present a 25-year-old left-handed female patient who fits the diagnostic criteria for NF-1. She presented with focal seizure and was diagnosed with grade 3 anaplastic meningioma, a highly aggressive tumor. She experienced a rapid recurrence after her initial surgery and eventually received multiple lines of treatments, including radiation and chemotherapy [temozolomide (TMZ)]. Conclusions: Systemic therapy in grade 3 meningiomas is still experimental and may have a slight clinical benefit. As a result, further prospective, multicentric studies are needed to ascertain these outcomes. Patients should be included in prospective trials because of the poor prognosis and aggressive nature of grade 3 meningiomas. In addition, discovering specific molecular biomarkers will allow us to suggest an individualized treatment. This case suggests that the differential diagnosis of a mass in a patient with NF-1 should include tumors known to be associated with the syndrome as well as sporadic, unrelated neoplasms.

Primary Intracranial Solitary Fibrous Tumor With Metachronous Pulmonary and Bone Metastasis: A Case Report.

An intracranial solitary fibrous tumor (SFT) is a rare and aggressive tumor with a high propensity for locoregional recurrence and distant metastasis. The formerly used collective term for this tumor, "solitary fibrous tumor/hemangiopericytoma", has recently fallen out of use and is now commonly replaced with the term "solitary fibrous tumor". We describe a rare case of intracranial SFT with simultaneous metastasis to the spine, the right humerus, and the lungs four years after resection and radiotherapy of the primary tumor.

Metastatic Type II Papillary Renal Cell Carcinoma With Recurrent Complete Responses to Sunitinib: A Case Report With a Literature Review.

Papillary renal cell carcinoma (PRCC) is a less common subtype of kidney cancer and is typically more resistant to systemic treatments. This report describes a patient with metastatic type II PRCC who experienced two complete responses (CR) to the tyrosine kinase inhibitor (TKI) sunitinib. The patient remains on sunitinib with durable control of the disease. To the best of our knowledge, this is the first case of metastatic type II PRCC with CR to sunitinib.

Exceptional Response to Second-Line Gemcitabine/Nab-Paclitaxel Chemotherapy in Patients With Metastatic Pancreatic Adenocarcinoma.

Pancreatic cancer is an extremely lethal malignancy with the majority of patients presenting with advanced disease. Typically, fit patients with advanced unresectable disease are treated with chemotherapy, which comprises either first-line folfirinox (FNX) or gemcitabine/nab-paclitaxel (GNP) regimens based on level 1 evidence. To our knowledge, robust evidence for second-line GNP post FNX does not exist. We herein report four cases treated at our institute with second-line GNP. Amongst those were patients with durable responses lasting over a year, which is extremely rare in stage 4 pancreatic cancer.

Fluoropyrimidine-Induced Severe Toxicities Associated with Rare DPYD Polymorphisms: Case Series from Saudi Arabia and a Review of the Literature.

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report cases from our institute with colorectal cancer who experienced severe toxicities to standard dose 5-FU based chemotherapy. DPYD gene sequencing revealed rare different polymorphisms that prompted dose adjustments of administered 5-FU and capecitabine. To our knowledge, this is the first case series looking at DPYD polymorphisms in the Saudi Arabian population.

Suggested Modifications to the Management of Patients With Breast Cancer During the COVID-19 Pandemic: Web-Based Survey Study.

BACKGROUND: Management of patients with cancer in the current era of the COVID-19 pandemic poses a significant challenge to health care systems. Breast cancer is the most common cancer internationally. Breast cancer is a disease that involves surgery, chemotherapy, hormonal therapy, targeted therapy, radiotherapy, and, more recently, immunotherapy in its management plan. The immune system requires months to recover from these medications, and this condition is even worse in patients with metastatic breast cancer who need ongoing treatment with these drugs. Some of these drugs, such as inhibitors of cyclin-dependent kinases 4 and 6, can cause rare but life-threating lung inflammation. Patients with breast cancer who have metastatic disease to the lungs can experience deterioration of disease symptoms with COVID-19 infection. Oncologists treating patients with breast cancer are facing a difficult situation regarding treatment choice. The impact that COVID-19 has had on breast cancer care is unknown, including how to provide the best care possible without compromising patient and community safety. OBJECTIVE: The aim of this study was to explore the views of oncologists regarding the management of patients with breast cancer during the COVID-19 pandemic. METHODS: A web-based SurveyMonkey questionnaire was submitted to licensed oncologists involved in breast cancer management in Saudi Arabia, Egypt, and United Arab Emirates. The survey focused on characteristics of the participants, infection risk among patients with cancer, and possible treatment modifications related to different types of breast cancer. RESULTS: The survey was completed by 82 participants. For early hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer, 61 of the 82 participants (74%) supported using neoadjuvant hormonal therapy in selected patients, and 58% (48/82) preferred giving 6 over 8 cycles of adjuvant chemotherapy when indicated. Only 43% (35/82) preferred inhibitors of cyclin-dependent kinases 4 and 6 with hormonal therapy as the first-line treatment in all patients with metastatic HR-positive disease. A total of 55 of the 82 participants (67%) supported using adjuvant trastuzumab for 6 instead of 12 months in selected patients with HER2-positive breast cancer. For metastatic HER2-positive, HR-positive breast cancer, 80% of participants (66/82) supported the use of hormonal therapy with dual anti-HER2 blockade in selected patients. The preferred choice of first-line treatment in metastatic triple negative patients with BRCA mutation and programmed cell death 1 ligand 1 (PD-L1) <1% was poly(adenosine diphosphate-ribose) polymerase inhibitor according to 41% (34/82) of the participants, and atezolizumab with nab-paclitaxel was preferred for PD-L1 >1% according to 71% (58/82) of the participants. CONCLUSIONS: Several modifications in breast cancer management were supported by the survey participants. These modifications need to be discussed on a local basis, taking into account the local infrastructure and available resources.

Sunitinib: An Unusual Cause of Pneumothorax in a Patient With Metastatic Chromophobe Renal Cell Carcinoma.

Spontaneous pneumothorax secondary to sunitinib, a vascular endothelial growth factor receptor (VEGFR) inhibitor, is an extremely rare side effect of this class of medications. In this report, we present the case of a patient with metastatic renal cell carcinoma (RCC) who developed bilateral pneumothoraces after starting on sunitinib. This case report recognizes pneumothorax as a life-threatening side effect of sunitinib.

Immediate Response to Chemotherapy in an Adult Neuroblastoma Patient Presenting with Cord Compression.

We report a case of a 31-year-old female patient with high-risk neuroblastoma (NBL) who presented with a history of static back pain and bilateral lower limb weakness for almost a month. Her primary tumor was located in the right paraspinal region, causing spinal cord compression (SCC). Chemotherapy was administered with an immediate clinical improvement noted after 24 hours of starting treatment. We herein report the efficacy of chemotherapy in an adult neuroblastoma (aNBL) patient presenting with spinal cord compression.

Early Stage Anaplastic Sarcomatoid Carcinoma of The Pancreas, A Case Report.

BACKGROUND Anaplastic sarcomatoid carcinoma of the pancreas (ASCP) is a rare variant of pancreatic malignancies. It is a high-grade epithelial carcinoma predominated with spindle cells. CASE REPORT We report a case of a 65-year-old patient who presented with early stage, ampullary mass indicating malignancy, and who subsequently underwent pancreatoduodenectomy. Histopathology and immunohistochemistry were confirmatory for anaplastic, grade IV sarcomatoid adenocarcinoma arising from the head of the pancreas. CONCLUSIONS To our knowledge, this is a rare presentation with few cases reported in the literature.

Identifying a Novel DPYD Polymorphism Associated with Severe Toxicity to 5-FU Chemotherapy in a Saudi Patient.

Dihydropyrimidine dehydrogenase (DPD) is the major enzyme in the catabolism of 5-Fluorouracil (5-FU) and its prodrug capecitabine. We report a 65-year-old female with rectal adenocarcinoma who experienced severe toxicities secondary to standard dose 5-FU based chemotherapy. She was found to be heterozygous for rs371313778, c.2434G>A. This finding prompted restarting 5-FU at 50% dose reduction with further titration in subsequent cycles. We herein report the first case of rs371313778, c.2434G>A (p.Val812lle) DPYD polymorphism leading to severe 5-FU toxicities. The patient eventually completed a 6-month course of adjuvant treatment with modification of 5-FU dose.

Performance Status Assessment by Using ECOG (Eastern Cooperative Oncology Group) Score for Cancer Patients by Oncology Healthcare Professionals.

Medical literature does not have clear consensus on inter-rater reliability of PS assessment by different oncology health care professionals (HCPs) although it plays an important role in treatment decision and prognosis for oncology patients. Eastern Cooperative Oncology Group (ECOG) and Karnofsky performance status (KPS) scores are commonly used for this purpose by oncology HCPs around the world. This study was conducted to find variability or similarities in assessment of PS among the different oncology HCPs. A survey based on four hypothetical clinical scenarios was devised and sent to 50 oncology HCPs to assess the PS using ECOG PS tool. No significant variations in PS assessment by oncology HCPs was noted in our study sample.

Predictors of cisplatin-induced ototoxicity and survival in chemoradiation treated head and neck cancer patients.

OBJECTIVES: Cisplatin-induced ototoxicity is a common permanent consequence of curative chemoradiation for locally advanced head and neck squamous cell carcinoma (HNSCC). Predictors of ototoxicity in HNSCC were examined. MATERIALS AND METHODS: In this prospective, observational cohort study, 206 adult HNSCC patients underwent audiometric testing at baseline, during and after treatment with cisplatin-based chemoradiation. Ototoxicity was defined as ≥grade 2 audiometric change from baseline (CTCAE v4.02). Relationships between clinical and pharmacogenetic (TPMT, COMT, ACYP2, CTR1, OCT2, MATE1, ABCC2, ABCC3, and ABCG2) covariates and ototoxicity, progression-free (PFS) and overall survival (OS) were assessed by Cox regression. RESULTS: Weekly cisplatin resulted in lower ototoxicity risk while PFS and OS were similar compared to high dose cisplatin (P = 0.00035; HR = 0.18; 95% CI, 0.07-0.46). COMT (rs9332377) carriers had higher ototoxicity risk (P = 0.00556; HR = 1.72; 95% CI, 1.17-2.52) while MATE1 (rs2289669) A/A carriers were protected from ototoxicity (P = 0.01062; HR = 0.46; 95% CI, 0.26-0.84). Absence of the protective MATE1 allele among those who carry the risk allele in COMT predicted increased ototoxicity risk, (P = 0.00414; HR = 3.22; 95% CI, 1.45-7.17 and P = 0.00022; HR = 4.89; 95% CI, 2.11-11.36). Survival outcomes did not differ between carriers of protective or risk alleles. CONCLUSIONS: Weekly cisplatin dosing, COMT and MATE1 are predictors of ototoxicity without affecting treatment efficacy. COMT and MATE1 genotyping and weekly dosing may be a potential strategy for mitigating cisplatin-induced ototoxicity in HNSCC.

Metastatic Cecal Adenocarcinoma to the Gallbladder Presenting with Acute Cholecystitis.

Colorectal cancer (CRC) is one of the most common cancers and the second highest cause of cancer-related deaths (Jemal et al., 2011). Common presentations of CRC include alterations in bowel habit, weight loss, and lower gastrointestinal bleeding. We report a case of a 74-year-old male who presented with fever and right upper quadrant pain, with positive Murphy's sign on examination. The case was initially managed with a routine cholecystectomy. Histological examination revealed a moderately differentiated adenocarcinoma with a superimposed histologically proven acute acalculous cholecystitis. CT scan done postsurgery showed a cecal mass with retroperitoneal lymphadenopathy. Biopsy result of cecal mass was remarkable for colon adenocarcinoma. We are not aware of any similar prior cases reported in English literature.

Awareness, understanding, attitude and barriers toward prescribing modern cancer immunotherapies in the Arabian Gulf countries.

INTRODUCTION: The use of modern immunotherapy has been evolving over the past few years, and various new agents have been developed for new indications at multiple primary sites in oncology. It is important for physicians who are involved in cancer care to be aware and updated about new therapeutic agents and their indications, potential benefits, and side effects. PATIENTS AND METHODS: From October to November 2017, we conducted a survey on the awareness, understanding, attitude, and barriers associated with prescribing modern cancer immunotherapies among physicians in the Arabian Gulf countries. The study included practicing physicians who delivered chemotherapy; trainees were not eligible. A total of 460 physicians were contacted and invited to complete an online survey, of which approximately 74.8% did not respond, and 4 (3.4%) were excluded because they had not recently treated patients with cancer. 112 (24.3%) physicians completed the survey (completion rate = 25.2%). An online electronic survey questionnaire was developed via Planet Surveys. The survey was designed with multidisciplinary inputs of the study investigators practicing in the Arabian Gulf countries, piloted, and subsequently revised on the basis of feedback from 10 additional oncologists. The final survey included 23 questions and took 8-10 minutes for completion. RESULTS: All respondents were aware of modern immunotherapies, but 62.5% reported having limited experience in implementing them, whereas 31.3% reported good experience. The overall physicians' attitudes toward modern immunotherapy were favorable, with a mean score of 7.4 (scale of 1-10, with 10 being extremely favorable). Efficacy, clear indications, and good safety profile were perceived as key potential benefits. Cost, lack of experience, and lack of access to specific testing were the major barriers. DISCUSSION AND CONCLUSION: There was a high level of awareness and an overall positive attitude toward modern cancer immunotherapy among oncologists in the Arabian Gulf countries, but there was a limited experience in prescribing cancer immunotherapeutic agents. Efficacy, clear indications, and good safety profile were perceived as key potential benefits, whereas cost, lack of experience, and lack of access to specific testing prior to prescription were the major barriers. Patients were likely to be receptive to modern immunotherapy as a therapeutic option for cancer treatment. Long-term efficacy data, financial support programs, and educational activities for prescribers may increase the access to modern immunotherapy.

Chronic Oxaliplatin-Based Chemotherapy in a Primary Ampullary Adenocarcinoma Patient without Significant Peripheral Neuropathy: Case Report and Literature Review.

Peripheral neuropathy is the most common dose-limiting toxicity associated with oxaliplatin. We report on a 61-year-old female patient with advanced primary ampullary adenocarcinoma who received 35 cycles of FOLFIRINOX (5-fluorouracil, irinotecan, and oxaliplatin) chemotherapy. The patient has tolerated this treatment without developing significant peripheral neuropathy.