Mohamed Alsharedi

Pancreatic cancer survival in elderly patients treated with chemotherapy.

Objectives Pancreatic cancer is a lethal disease mostly affecting elderly people. Clinical trials on treatment contain disproportionately fewer elderly patients compared with everyday practice. This retrospective study evaluates differences in the rates of chemotherapy delivered and associated survival in different age groups. Methods Data were collected from the Cancer Information Resource Files on patients diagnosed with pancreatic cancer from 1993 to 2008. Patients were divided into 3 age groups, namely, A with younger than 50 years, B with 50 to 70 years old, and C with older than 70 years. Results Complete data were available on 16,694 patients. Forty-four percent were in group C. Chemotherapy was given to 38% of patients in group C versus 69% of patients in group A. A multivariate analysis revealed a similar chemotherapy benefit in all groups, as follows: group C (hazard ratio [HR], 0.51), group A (HR, 0.74), and group B (HR, 0.55). Conclusions We found that elderly patients with pancreatic cancer receive treatment less frequently compared with younger patients. However, elderly patients receiving chemotherapy derive similar benefits. Randomized clinical trials are needed to evaluate pancreatic cancer treatment in the elderly patients, particularly given the increasing occurrence of pancreatic cancer in later life.

Immunotherapy in triple-negative breast cancer

Breast cancer can be classified based on the expression or lack of expression of protein receptors including estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (Her2). The basal molecular subtype is mostly made up of breast cancers that do not express ER/PR or Her2, triple-negative breast cancers (TNBC) (Bertucci et al. in Int J Cancer 123(1):236, 2008). TNBC tends to be more aggressive as there are no approved targeted treatments and the only treatment option currently is cytotoxic chemotherapy. Recent data show that some chemotherapies, specifically anthracyclines, not only have cytotoxic effects but also use the immune system by activating CD8+ T cell responses to kill cancer cells (Stagg et al. in Ther Adv Med Oncol 5(3):169–181, 2013), and thus, tumor-infiltrating lymphocytes respond well to chemotherapy. Currently, systemic immunotherapy which utilizes the patient’s own immune system directly to eradicate and target neoplastic cells is being explored as treatment for TNBC as this type of breast cancer has been shown to be immunogenic (Yu et al. in Int J Environ Res Public Health 14:68, 2017). According to the Cancer Genome Atlas, TNBC has higher PD-L1 mRNA expression (Mittendorf et al. Cancer Immunol Res 2(4):361–370, 2014). Higher rates of CD8+ T cell infiltration were also found in TNBC according to a study by Liu et al. (Breast Cancer Res 14:R48, 2012). In TNBC patients, Pembrolizumab, a monoclonal antibody that targets programmed cell death protein 1 (PD-1), and Atezolizumab, a monoclonal antibody that targets its ligand, have been investigated to assess dose tolerability and side effects. Further studies involving vaccines, immunotherapy that targets cytotoxic T lymphocyte-associated protein-4 and PD-L1, are currently being investigated for treatment of TNBC. This review outlines the systemic immunotherapies that are currently being investigated for patients with TNBC.

Check point inhibitors a new era in renal cell carcinoma treatment

In the United States, the estimated number of new cases of renal cell carcinoma (RCC) is approximately 65,000 case with about 15,000 deaths in the year of 2018 (Siegel et al. in CA Cancer J Clin 68(1):7, 2018). RCC as an immunogenic malignancy is supported by many theories and facts which include tumor richness of lymphocytes infiltrate, the occurrence of spontaneous tumor regression, and the proved effect of traditional immunotherapy (Finke et al. in J Immunother 11(1):1–11, 1992), all these factors support the potential therapeutic effect of the novel immunotherapeutic agents in RCC. Historically, complete tumor regression in metastatic RCC is achievable in a minority of patients through traditional immunotherapies such as high-dose interleukin-2 (IL-2) (Fyfe et al. in J Clin Oncol 13(3):688, 1995) and interferon-alfa (IFNa) (Negrier et al. in N Engl J Med 338(18):1272, 1998); however due to the significant rate of toxicities and low efficacy; accordingly the targeted therapy with tyrosine kinase inhibitors (TKIs) and vascular endothelial growth factor-antibodies (VEGF) became the standard and prevalent treatment approach for advanced RCC both in front and subsequent lines of therapy (Escudier et al. in Ann Oncol. 25(Suppl 3):iii49–iii56, 2014). A new avenue of immunotherapy utilizing novel strategy to block immune checkpoints has emerged in a new era for RCC treatment (Ascierto et al. in J Transl Med 12:291, 2014). Results from clinical trials are encouraging in both front-line and second-line settings, in a phase III trial (CheckMate 025) nivolumab compared to everolimus improved overall survival in previously treated metastatic RCC who had progressed on prior treatment with targeting agents (Motzer et al. in N Engl J Med 373:1803, 2015). CheckMate 214, a phase III trial, demonstrated superior overall survival and objective response with combined checkpoint inhibitors compared to sunitinib in Treatment-Naïve Advanced RCC among intermediate- and poor-risk group (Motzer et al. in N Engl J Med. 378(14):1277–1290, 2018). In this review, we discuss the systemic Immunotherapy with checkpoint inhibitors that have been approved or are currently being investigated in RCC, clinical experience with these agents, and its future development.

Chemotherapy-related acute respiratory distress syndrome in germ cell tumors: a literature review

Germ cell tumors (GCTs) are one of the more curable solid cancers in men. Approximately 8500 men are diagnosed with GCTs in the USA. The majority of patients survive due to the availability of effective treatment. Fewer than 400 men are estimated to die from their disease. Among those, there is a subset of patients with metastatic GCTs receiving chemotherapy who rapidly develop progressive respiratory failure and die during the early phase of their treatment course. In this review, we searched the available literature for reported cases and retrospective series of chemotherapy-associated acute respiratory distress syndrome in GCTs. We aim to determine whether a different approach from current treatment guidelines could be considered to prevent this catastrophic chemotherapy-related event.

Bilateral Triple-Negative Invasive Breast Cancer with a BRCA2 Mutation, and Glioblastoma: A Case Report and Literature Review

Breast cancer is the second leading cause of death among women in North America. Glioblastoma is the most common primary malignant central nervous system tumor in adults. The majority of hereditary breast cancers are associated with deleterious mutations in the BRCA1 and BRCA2 genes. Although few case reports have described the incidence of glioblastoma in patients previously diagnosed with breast cancer, any association between BRCA2 mutations and glioblastoma has not been demonstrated to date. Herein, we report a woman who is a carrier of a familial BRCA2 mutation, and was previously diagnosed with triple-negative breast cancer (TNBC) and subsequently with a second primary TNBC and glioblastoma. Further investigation is required to define the possible relationship between these two aggressive malignances and the BRCA2 mutation, which might be critical for the proper management and treatment of this disease.

Leukemia cutis in a patient with chronic lymphocytic leukemia presenting as bilateral helical nodules

Chronic lymphocytic leukemia, the most common adult leukemia worldwide, is considered an indolent but incurable non-Hodgkin lymphoma. Leukemia cutis is an uncommon manifestation of chronic lymphocytic leukemia. We present a case of an adult patient who presented with skin lesion of bilateral ears, which led to the diagnosis of chronic lymphocytic leukemia. We also reviewed the cases of auricular involvement in chronic lymphocytic leukemia patients reported in the literature. Local treatment is indicated in case of leukemia cutis; however, systemic treatment is recommended when there are systemic signs and symptoms. Better awareness of disease evolution and prompt diagnosis of this leukemia cutis of chronic lymphocytic leukemia will improve the effectiveness and outcome of its management.

Primary Retroperitoneal Melanoma Presented in a Rare Extracutaneous Site for Malignant Melanoma

Malignant melanoma, as the name implies, is a malignant tumor of melanocytes, found in the skin, eyes, meningeal lining and the mucosal epithelium of the aero-digestive and genitourinary tracts. Malignant melanoma is typically skin malignancy, which rarely presents at extracutaneous site. Here we present a rare case of primary retroperitoneal melanoma and review the findings in comparison with other cases described in literature.

Metastatic Sarcomatoid Carcinoma of the Small Intestine: a Case Report of Rare Tumor with Literature Review

Sarcomatoid carcinoma (SCA) is an uncommon variant of small intestinal carcinoma with both carcinomatous and sarcomatous features [1–3]. Gastrointestinal SCA has been described in the gall bladder, stomach, esophagus, and colon, but is rarely reported in the small bowel, with less than 30 cases reported to date in the literature in English [1]. The natural history of this unusual tumor and the best treatment approach are unknown. A patient with jejunal SCA usually presents with a large tumor which is likely a reason for the poor outcome as compared to esophageal and gastric ones which usually present early with small tumor causing obstructive symptoms. We present a case of SCA arising from the jejunal mucosa with findings from both morphological and immunohistochemical studies.

Immunotherapy in a rare case of primary pelvic retroperitoneal melanoma

Recent advances in novel immunotherapeutic and targeted therapeutic agents have increased treatment options in patients with advanced metastatic melanoma. However, evidence in the literature on whether or not extracutaneous melanoma will acquire an equivalent advantage from these therapies is very scarce. In general, extracutaneous melanomas are rare and aggressive melanomas, which are clinically and biologically unique, with higher incidence of metastatic disease and poor prognosis. In this case report, we present a very rare case of a 54-year-old woman with primary pelvic retroperitoneal melanoma treated with an anti-PD-1 antibody, pembrolizumab. Furthermore, we explore the role of novel immunotherapies in the treatment of advanced melanoma.