Role of Cytoreductive Nephrectomy in Metastatic Clear Cell Renal cell Carcinoma in the Era of immunotherapy: An Analysis of the National Cancer Database.

BACKGROUND: The effectiveness of the clinical outcome of CN (Cytoreductive Nephrectomy) in cases of mccRCC (Metastatic Clear Cell Renal cell Carcinoma) is still uncertain despite two trials, SURTIME and CARMENA. These trials, conducted with Sunitinib as the standard treatment, did not provide evidence supporting the use of CN. METHODS: We queried the NCDB for stage IV mccRCC patients between the years of 2004 to 2020, who received (immunotherapy) IO with or without nephrectomy. Overall survival (OS) was calculated among three groups of IO alone, IO followed by CN (IOCN), CN followed by IO (CNIO). Cox models compared OS by treatment group after adjusting for sociodemographic, health, and facility variables. RESULTS: From 1,549,101 renal cancer cases, 7983 clear and nonclear cell renal cell carcinoma cases were identified. After adjusting for sociodemographic and health covariates, patients who received IO followed by CN or CN followed by IO had a respective 64% (adjusted Hazard Ratio [aHR] = 0.36, 95% CI = 0.30-0.43, P = .006] and 47% (aHR = 0.53, 95% CI = 0.49-0.56, P = .001) mortality risk reduction respectively compared to patients who received IO alone. Compared to White adults, individuals who identified as Black exhibited 17% higher risk mortality (aHR = 1.17, 95% CI = 1.06-1.30, P = .002). Patients who received CN prior to IO had a 59% associated mortality risk compared to patients who received IO followed by CN who had a lower risk, 35.7% (P < .001). CONCLUSIONS: Patients receiving CN regardless of sequence with IO did better than IO alone in this national registry-based adjusted analysis for mccRCC. Presently available data indicates that the combination of CN and IO holds promise for enhancing clinical results in patients with mRCC.

Radiation Recall Dermatitis Following Treatment With Pembrolizumab: A Case Report and Review of the Literature.

Radiation recall dermatitis is an inflammatory reaction of the skin that may infrequently occur in areas of the skin that have been previously treated with radiation therapy. This is thought to be due to a triggering agent administered after radiation therapy which leads to an acute inflammatory reaction, manifesting as a skin rash. We present the case of a 58-year-old male with recurrent invasive squamous cell carcinoma of the tongue, previously treated with chemotherapy and radiation therapy, who presented with progression of his disease. He was treated with pembrolizumab and subsequently developed a new-onset facial rash over the previously treated radiation field. The distribution of the rash was suggestive of radiation recall dermatitis. A biopsy showed dermal necrosis without evidence of dermatitis, vasculitis, or infectious process. This case highlights the incidence of a rare complication of immune checkpoint inhibitor therapy and emphasizes the need for careful monitoring for radiation recall dermatitis.

Efficacy of chemotherapy in patients with HR+/HER2-Invasive lobular breast cancer.

INTRODUCTION: Invasive Lobular Breast Cancer (ILC) harbors unique clinicopathologic features. Data on optimal treatment modalities focusing on ILC remain scarce. We aim to investigate the benefit of chemotherapy in early-stage hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) ILC. METHODS: Female patients with early HR+/HER2- ILC (stages I-III) who underwent surgery were selected from the National Cancer Database (2010-2016) and grouped into four treatment cohorts: surgery only(S), chemotherapy alone (CT), endocrine therapy alone (ET), and combined chemotherapy followed by endocrine therapy (CET). Descriptive and bi-variate statistics summarized baseline characteristics and compared them across cohorts. A secondary analysis accounting for OncotypeDX (ODX) information was performed, stratifying for low (<26) and high (≥26) ODX. Kaplan-Meier (KM) and Cox proportional hazard models evaluated the relationship between treatment modality and overall survival (OS), stratifying for ODX scoring. RESULTS: N = 15,271 patients were included. The CET cohort (29.8%) was more likely to be younger and have no co-morbidities, advanced tumor stage or high ODX score (≥26). No significant difference in OS comparing ET to CET (HR:1.08, 95%CI:0.93-1.26, p = 0.31) was observed, adjusting for confounders. N = 5,561 patients had ODX results available. No significant difference in 5-year OS was observed comparing the ET to CET cohorts, both in patients an ODX score <26 (HR:1.10; 95%CI:0.69-1.76, p = 0.69) and ODX score ≥26 (HR:1.18; 95%CI:0.51-2.75, p = 0.69). CONCLUSION: Chemotherapy demonstrated no added survival benefit in HR+/HER2- ILC, even in tumors with ODX ≥26. Prospective trials identifying potential subgroups of patients with ILC who could benefit from chemotherapy are needed.

Value of chemotherapy post immunotherapy in stage IV non-small cell lung cancer (NSCLC).

BACKGROUND: Lung cancer is the number one cause of mortality among all types of cancer worldwide. Its treatment landscape has shifted from the classic chemotherapy alone to newer regimens based on the discovery of new immunotherapy and targeted therapy drugs. However, chemotherapy is still an option for treatment of advanced non-small cell lung cancer (NSCLC) after progression on immunotherapy alone or in combination with first-line chemotherapy. METHODS: This is a retrospective study based on chart review of patients diagnosed with advanced NSCLC cases who received Docetaxel as second or third line after being treated by immunotherapy and/or chemotherapy in previous lines. The data was collected from the medical records of physicians' clinics in three different hospital centers in Lebanon over the period of 5 years from July 2015 until December 2020. February 2021 was data analysis cut off time. The main aim was to assess the role of Docetaxel post-chemoimmunotherapy for patients with diagnosed NSCLC. RESULTS: A total of 21 patients were included in this study. The majority of our patients were males (81%). As for histologic type, most patients had non-squamous lung cancer (67%) as compared to 33% who had squamous lung cancer. Overall, our study reported a 24% response rate to Docetaxel including stable disease and partial response and a median progression free survival (PFS) of 3 months. The mean time interval elapsed from diagnosis to the initiation of Docetaxel was 11.5 months. CONCLUSION: New therapeutic options should be validated for the treatment of NSCLC in the second and subsequent lines of therapy considering the poor prognosis of this disease. The chemotherapy in second and third line may keep an important role in the treatment after progression on newer agents, but it needs more evidence in prospective studies including a larger number of patients.

The Urogenital System's Role in Diseases: A Synopsis.

The human microbiota contains ten times more microbial cells than human cells contained by the human body, constituting a larger genetic material than the human genome itself. Emerging studies have shown that these microorganisms represent a critical determinant in human health and disease, and the use of probiotic products as potential therapeutic interventions to modulate homeostasis and treat disease is being explored. The gut is a niche for the largest proportion of the human microbiota with myriad studies suggesting a strong link between the gut microbiota composition and disease development throughout the body. More specifically, there is mounting evidence on the relevance of gut microbiota dysbiosis in the development of urinary tract disease including urinary tract infections (UTIs), chronic kidney disease, and kidney stones. Fewer emerging reports, however, are suggesting that the urinary tract, which has long been considered 'sterile', also houses its unique microbiota that might have an important role in urologic health and disease. The implications of this new paradigm could potentially change the therapeutic perspective in urological disease.

Drug-Induced Peripheral Neuropathy: Diagnosis and Management.

Peripheral neuropathy comes in all shapes and forms and is a disorder which is found in the peripheral nervous system. It can have an acute or chronic onset depending on the multitude of pathophysiologic mechanisms involving different parts of nerve fibers. A systematic approach is highly beneficial when it comes to cost-effective diagnosis. More than 30 causes of peripheral neuropathy exist ranging from systemic and auto-immune diseases, vitamin deficiencies, viral infections, diabetes, etc. One of the major causes of peripheral neuropathy is drug-induced disease, which can be split into peripheral neuropathy caused by chemotherapy or by other medications. This review deals with the latest causes of drug-induced peripheral neuropathy, the population involved, the findings on physical examination and various workups needed and how to manage each case.

Glioblastoma multiforme metastasizing to the skin, a case report and literature review.

Glioblastoma Multiforme (GBM) is the most common primary central nervous system (CNS) malignancy in adults. It is very aggressive and is notorious for its fast and local invasion of nearby brain parenchyma. Consequently, the overall survival (OS) of patients with GBM is short despite resection, radiotherapy and chemotherapy regimens. The most common sites of metastasis of GBM are the lungs and pleura, cervical lymph nodes, and bone. Metastasis to the skin is a rare event and to our knowledge, there are less than 30 cases of GBM metastasizing to cutaneous or subcutaneous tissue described in the literature. None of these cases were diagnosed and/or treated in the Middle East region; and the majority of the metastases found were adjacent to the site of surgery undergone to remove the primary malignancy. We present the case of a 53-year-old male diagnosed with GBM and later showing signs of metastases at the anterio-auricular side of his face near-distant from the site of previous surgery done to remove the primary tumor.

Radioimmunoconjugates in the age of modern immuno-oncology.

Immunotherapy was first investigated as a therapeutic option for treating cancer more than a century ago. During this period, it has gone through numerous disappointments when the successes obtained in the laboratory were not matched clinically. However, recent advances in immuno-oncology have provided the impetus to revisit this therapeutic option. Unlike previous efforts, modern immunotherapy is now a realistic and formidable therapeutic option for patients with relapsed/refractory malignancies. Unfortunately, most of the successes obtained thus far have primarily been in patients with hematologic malignancies. While the results of immunotherapy with immune check-point inhibitors for solid tumors such as non-small cell lung cancer and melanoma are encouraging, more effective treatment methods are desirable. Many intrinsic and extrinsic factors pose as obstacles to successful immunotherapy of solid tumors. They include heterogeneity of tumor antigens, limitation in the trafficking and accessibility of the effector mechanisms to the tumor sites, the adverse anti-inflammatory tumor microenvironment, and the on-target off tumor and off-target off-tumor effects of some of these approaches. In this review, we will discuss these obstacles and examine the evidence that support the notion that radioimmunotherapy, using radioimmunoconjugates, may be the answer to overcome these obstacles in patients with metastatic cancer. Finally, we will discuss how the efficacy of radioimmunotherapy using radioimmunoconjugates might further be harnessed to maximize successes in these patients.

Safety and efficacy of pazopanib as a second-line treatment and beyond for soft tissue sarcomas: A real-life tertiary-center experience in the MENA region.

INTRODUCTION: Sarcomas are uncommon malignancies. No advances have been recently achieved despite multiple efforts. Pazopanib is a safe and effective tyrosine kinase inhibitor used in managing soft tissue sarcomas (STS) after chemotherapy failure. However, its use is limited in developing countries and no efficacy data exist from our region. We aimed to study the efficacy of pazopanib in our population, characterized by response rates of patients with chemotherapy-refractory advanced STS receiving pazopanib. Secondary endpoints included progression-free survival (PFS), overall survival (OS) and toxicity profile. MATERIALS AND METHODS: 15 patients (age≥18 year) diagnosed with advanced STS, refractory to first-line chemotherapy, receiving pazopanib as ≥second-line therapy in one tertiary center in Lebanon were included between January 1st, 2014 and October 31st, 2018. Patient and disease characteristics, disease evaluation, as well as tolerance to treatment, were extracted from charts retrospectively. Statistical analysis was done using SPSS version 24. RESULTS: The mean age was 48.6 [19-66] years. Eleven patients (73.3%) received pazopanib in second-line, whereas four patients (26.7%) received it in third-line. Thirteen patients (86.7%) progressed, and two patients (13.3%) had stable disease. The median PFS was three months [1-19] and the mean OS was 25.4 months [17.2-33.6]. Five patients required dose-reductions due to poor tolerance. CONCLUSION: Conclusions cannot be drawn due to small patient numbers. However, given the 3-month PFS, 13% of patients maintaining stable disease, and tolerable safety profile, it is reasonable to incorporate pazopanib in STS treatment. More focused studies with larger patient populations need to be done in Lebanon.