Konstantinos Arnaoutakis

Lung Cancer in Octogenarians

Background: Lung cancer has progressively become a disease of older people, with the median age at diagnosis now exceeding 70 years. Octogenarians represent a rapidly growing proportion of patients diagnosed with lung cancer and can present distinct challenges. Nevertheless, current literature that has set the evidence-based standards of care in this disease does not include significant numbers of patients older than 80 years. Methods: We have compiled and reviewed the available literature on the specific management and treatment of lung cancer in patients older than 80 years. Results: Retrospective series suggest that surgery is safe and effective in treating early-stage non-small cell lung cancer in selected patients older than 80 years. There is minimal data to support the use of adjuvant chemotherapy in this group. In addition, no data exist on the use of combined chemotherapy and radiotherapy for locally advanced disease. In advanced or metastatic disease, similar to younger elderly populations, single-agent chemotherapy is feasible and seems to offer benefit in terms of symptoms and outcomes. Small cell lung cancer in this population is not well characterized, but small studies suggest symptom improvement and prolongation of survival with the use of chemotherapy. Conclusion: Based on retrospective series, octogenarians with lung cancer can derive benefit from many of the treatment modalities used for younger patients including surgery for early-stage disease and single-agent chemotherapy for advanced disease. More elderly specific trials are needed to better refine treatment decisions and improve the care of lung cancer in this group.

Bronchus-associated lymphoid tissue lymphomas.

Background: Bronchus-associated Lymphoid Tissue (BALT) lymphomas are a rare type of extranodal marginal zone lymphomas. They comprise 1% of lymphomas and more than two-thirds of all primary non-Hodgkin lymphoma (NHL) of the lung. BALT lymphomas arise from the bronchus-associated lymphoid tissue. Methods: This report describes five cases of BALT lymphoma and discusses the pathogenesis, diagnosis, prognosis and treatment of BALT lymphomas. Results: In our cohort of patients, patients were managed with surgery, watchful waiting, chemotherapy, immunotherapy, and chemoimmunotherapy. The outcomes are excellent and projected 5-year survival is 100%. Discussion: BALT lymphomas are associated with chronic inflammation, and they are often asymptomatic. They have an indolent course and the survival outcome is excellent with different treatment modalities such as surgery, watchful waiting, radiotherapy, chemotherapy, immunotherapy or chemoimmunotherapy.

Targeting nano drug delivery to cancer cells using tunable, multi-layer, silver-decorated gold nanorods

Multifunctional nanoparticles have high potential as targeting delivery vehicles for cancer chemotherapy. In this study, silver‐decorated gold nanorods (AuNR\Ag) have been successfully used to deliver specific, targeted chemotherapy against breast cancer (MCF7) and prostate carcinoma (PC3) cell lines. Doxorubicin, a commonly used chemotherapy, and anti‐Epithelial cell adhesion molecule (anti‐EpCAM) antibodies were covalently bonded to thiolated polyethylene glycol‐coated AuNR\Ag, and the resultant system was used to deliver the drugs to cancer cells in vitro. Furthermore, these nanoparticles have a unique spectral signature by surface enhanced Raman spectroscopy (SERS), which enables reliable detection and monitoring of the distribution of these chemotherapy constructs inside cells. The development of interest in a plasmonic nano drugs system with unique spectroscopic signatures could result in a clinical approach to the precise targeting and visualization of cells and solid tumors while delivering molecules for the enhanced treatment of cancerous tumors.

Hyalinizing Clear Cell Carcinoma of the LungCase Report and Review of the Literature

Objectives Hyalinizing clear cell carcinoma (HCCC) is common in head and neck sites but extremely rare in the lung. This case report describes an HCCC in the lung of a 54-year-old female patient. Methods We summarize the histomorphologic, immunophenotypic, and molecular features for our and three previously reported HCCCs of the lung with emphasis on potential diagnostic pitfalls. Results Sections of a well-circumscribed 3.5-cm lung mass were characterized by a bronchocentric tumor growing in sheets, nests, and cords in a background of hyalinized stroma. Tumor cell appearance was clear to eosinophilic, lacking significant pleomorphism or mitotic activity. By immunohistochemistry, the tumor cells were strongly positive with antibodies to pan-keratin, p63, and CK5/6 while negative for CK7, CK20, thyroid transcription factor 1, napsin A, chromogranin, and synaptophysin. Next-generation sequencing demonstrated an EWSR1-ATF1 fusion transcript. Conclusions Awareness of key morphologic features of pulmonary HCCC is crucial for the recognition of this rare entity in the lung. Ancillary studies, including immunohistochemistry and molecular testing, are essential for the distinction from its mimics.

Simulating Four Essential Conversations with Hematology/Oncology Trainees: a Qualitative Evaluation.

Hematologists/oncologists have a crucial responsibility to effectively communicate with patients. However, they have been criticized for ineffective communication with patients. To develop effective communication behaviors that meet the needs of patients and families, trainees need practice and feedback about their performance. Medical faculties frequently teach communication skills using simulation-based curricula; however, they often include only general communication skills, without tailored approaches for specialties. This study examined Hematology/Oncology trainees’ qualitative perceptions about the value of and techniques used for simulations of specialty specific, essential conversations with patients and families, and debriefing sessions. Results demonstrate a highly effective curriculum and positive learner experiences. While most reports on this topic take place within major academic cancer centers, outcomes from a mid-sized Hematology/Oncology training program are unknown. The study confirms feasibility for implementing a simulation-based communications program in a mid-sized Hematology/Oncology program and describes simulation techniques that were effective.

Primary bone marrow Hodgkin lymphoma in an HIV-negative patient

Abstract Classical Hodgkin lymphoma has distinct clinicopathological features and shows good response to treatment in most cases. Primary bone marrow-limited Hodgkin lymphoma is uncommon and primarily described in HIV-positive patients. It behaves as a distinct entity with aggressive clinical course and poor response to available treatments. We discuss here a case of Hodgkin lymphoma with isolated involvement of bone marrow in an HIV-negative patient, which was successfully treated with conventional chemotherapy.

Liquid biopsy and its role in an advanced clinical trial for lung cancer

Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the “right” cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary and metastatic lesions. Regarding the assessment of response to cancer therapy, the liquid biopsy is not ready to replace medical imaging, but adds critical new information; for instance, through a temporal assessment of quantitative circulating tumor DNA (ctDNA) assay results, and importantly, the ability to monitor for signs of resistance, via emerging clones. Adjuvant therapy may soon be considered based on a quantitative cfDNA assay. As sensitivity and specificity of the technology continue to progress, cancer screening and prevention will improve and save countless lives by finding the cancer early, so that a routine surgery may be all that is required for a definitive cure.

Paralyzed by a rare cause: an unusual case of metastatic diffuse large B cell lymphoma of the intramedullary spinal cord

Dear Editor, Diffuse large B cell lymphoma (DLBCL) has been known to occur in the central nervous system (CNS) as primary CNS lymphoma [1] or as secondary involvement from a systemic disease. DLBCL has been rarely reported to present as intramedullary spinal cord metastasis (ISCM) [2]. Our patient, Ms. A, was a 74-year-old female diagnosed with DLBCL 1 year prior to her presentation due to a pelvic mass involving the left sacroiliac joint. She completed six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone followed by radiation to the mass. She did well for about 3 months. Three months later, she developed progressive lower extremity weakness. She was seen a few months later in our institution. She had urinary and bowel incontinence on admission. Exam on admission revealed symmetric sensory loss extending from bilateral lower extremities and paralysis. An MRI was contraindicated due to the presence of an incompatible cardiac pacemaker. Hence, a CT myelogram was performed which revealed expansion of the upper thoracic cord at the level of fourth and fifth thoracic vertebrae, suggestive of an intramedullary lesion (Fig. 1a, b). Bone marrow biopsy was normal. LP showed no evidence of malignancy or of a clonal population. PET/CT showed increased metabolic activity along the spinal cord canal involving the third, fourth, and fifth thoracic vertebral levels without osseous deformity (Fig. 1c, d), strongly suggestive of recurrent disease. PET/CT scan did not show disease elsewhere. Due to the high possibility for a lymphomatous process, she was started on steroids and she was evaluated by neurosurgery service. She underwent biopsy and subtotal resection of the intramedullary tumor with laminectomies of T3 through T5 vertebra. Pathology of the operative specimen revealed diffuse large B cell lymphoma, consistent with a germinal center origin. The surgical intervention, however, did not result in any clinical improvement. Since she was not a candidate for systemic chemotherapy, radiation therapy was initiated, but the treatment remained incomplete due to development of acute respiratory failure from healthcareassociated pneumonia. Intrathecal chemotherapy was also discussed, but she did not receive it since her condition continued to worsen necessitating ICU admission. At this point, given the paucity of clinical options and grim prognosis, the family decided to make her comfort care. The intramedullary spinal cord is a rare location for tumor metastasis, most commonly associated with lung and breast cancer [3, 4]. Intramedullary spinal cord metastasis from diffuse large B cell lymphoma has been very rarely reported in the literature. A recent case series from Mayo clinic [2] detailed the presentation of seven patients with non-Hodgkin’s lymphoma and ISCM over the course of 14 years. Three of these patients had pathology-proven DLBCL. Although the most common modality used for detection is the MRI, if this is contraindicated as in our case, a combination of CT myelography and PET can lead to localization of the metastatic lesion. Various therapeutic approaches have been made to treat the ISCM, but the results have been poor. However, as suggested by existing A. Rao Department of Medicine, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205, USA

CMV esophagitis: sequelae of radiation therapy

Cytomegalovirus (CMV) infection has been commonly described in immunocompromised patients. Antiretroviral therapy in HIV patients and routine antiviral prophylaxis in transplant recipients have helped to curb the majority of clinically significant CMV infections. Patients undergoing chemotherapy are also closely monitored for leucopenia and opportunistic infections. We describe here a case of CMV esophagitis in a patient with a solid tumor and no prior exposure to chemotherapy. This patient was immunocompromised from his recent radiation therapy and concurrent steroid use. This case demonstrates the fact that even without any exposure to chemotherapy, extensive radiation treatment can lead to severe marrow suppression. Early endoscopy in such patients is recommended to avoid delay in the diagnosis of opportunistic infections.

A novel prostate cancer immunotherapy using prostate-specific antigen peptides and Candida skin test reagent as an adjuvant

Objectives: Our group developed the use of the Candida skin test reagent as an adjuvant of cell-mediated immunity in designing a human papillomavirus therapeutic vaccine. Here, this technology is being applied for designing a prostate cancer immunotherapy. Methods: Peptides based on the prostate-specific antigen amino acid sequences were selected, synthesized, and evaluated in terms of their (1) solubility, (2) maturation effects on Langerhans cells by fluorescence-activated cell sorter analysis, and (3) recognition by peripheral immune cells from prostate cancer patients using interferon-γ enzyme-linked immunospot assay. Results: The peptides were soluble in 10 mM succinate at pH of 5 with 5% glycine, and they demonstrated no maturation effects on Langerhans cells from healthy donors. On the other hand, peripheral immune cells from 4 of 10 prostate cancer patients examined had positive responses in enzyme-linked immunospot assay to one or more prostate-specific antigen peptides. Conclusion: In summary, a design and a formulation of a novel prostate cancer immunotherapy are described. The immunogenicity of prostate-specific antigen peptides in some prostate cancer patients supports further development of this immunotherapy.