Prolonged Response of Metastatic Programmed Death-Ligand 1 (PD-L1) Negative Basaloid Squamous Cell Carcinoma of the Lung to Maintenance Immunotherapy.

Basaloid squamous cell carcinoma (BSCC) is a variant of squamous cell carcinoma that is most often seen as a variety of primary head and neck cancers. BSCC of the lung is rare primary lung cancer and an uncommon histological subtype of non-small cell lung carcinoma. Due to its rarity, there is little published information and research available to direct disease-specific management of BSCC of the lung. Most published cases of basaloid carcinoma of the lung report on surgical management of eligible patients and even less information can be found for metastatic cases. We report a case of a 74-year-old male with stage four (IV) BSCC of the lung who experienced a complete metabolic with partial anatomic response to combined chemotherapy and immunotherapy with carboplatin/nab-paclitaxel/pembrolizumab and has continued to be in partial remission on maintenance immunotherapy with pembrolizumab despite PD-L1-negative status.

Characterization of KRAS Mutation Subtypes in Non-small Cell Lung Cancer.

KRAS is the most commonly mutated oncogene in NSCLC and development of direct KRAS inhibitors has renewed interest in this molecular variant. Different KRAS mutations may represent a unique biologic context with different prognostic and therapeutic impact. We sought to characterize genomic landscapes of advanced, KRAS-mutated non-small cell lung cancer (NSCLC) in a large national cohort to help guide future therapeutic development.Molecular profiles of 17,095 NSCLC specimens were obtained using DNA next-generation sequencing of 592 genes (Caris Life Sciences) and classified on the basis of presence and subtype of KRAS mutations. Co-occurring genomic alterations, tumor mutational burden (TMB), and PD-L1 expression [22C3, tumor proportion score (TPS) score] were analyzed by KRAS mutation type.Across the cohort, 4,706 (27.5%) samples harbored a KRAS mutation. The most common subtype was G12C (40%), followed by G12V (19%) and G12D (15%). The prevalence of KRAS mutations was 37.2% among adenocarcinomas and 4.4% in squamous cell carcinomas. Rates of high TMB (≥10 mutations/Mb) and PD-L1 expression varied across KRAS mutation subtypes. KRAS G12C was the most likely to be PD-L1 positive (65.5% TPS ≥ 1%) and PD-L1 high (41.3% TPS ≥ 50%). STK11 was mutated in 8.6% of KRAS wild-type NSCLC but more frequent in KRAS-mutant NSCLC, with the highest rate in G13 (36.2%). TP53 mutations were more frequent in KRAS wild-type NSCLC (73.6%).KRAS mutation subtypes have different co-occurring mutations and a distinct genomic landscape. The clinical relevance of these differences in the context of specific therapeutic interventions warrants investigation.

Diagnosis and management of cold agglutinin disease associated with low-grade B-cell lymphoma in a patient receiving pembrolizumab for lung cancer.

A 65-year-old with non-small cell lung cancer developed autoimmune haemolytic anaemia while receiving pembrolizumab containing chemoimmunotherapy. Initially thought to be due to pembrolizumab induced haemolysis, he was treated with steroids, and pembrolizumab was held. Haemolysis was refractory to steroids and blood was observed to agglutinate in cold room temperatures. Cold agglutinins in high titre and monoclonal serum IgM kappa protein were detected. Bone marrow biopsy showed marginal zone lymphoma confirming low grade B-cell lymphoma causing cold agglutinin disease. B-cell depletion by rituximab stopped haemolysis, and pembrolizumab was safely continued for lung cancer.

Stenting in Non-Small Cell Lung Cancer: How Does It Affect the Outcomes?

OBJECTIVE: Approximately 30% of lung cancer patients develop central airway obstruction (CAO) that remarkably shortens survival. There is little data about the benefits of stenting within this heterogeneous patient group. Our objective was to review their overall survival (OS) and their risk of hospitalization versus patients who did not have lesions requiring stent placement. METHODS: We retrospectively reviewed charts of 171 non-small cell lung cancer (NSCLC) patients who underwent bronchoscopy in the University of Cincinnati Cancer Center from the year 2011 to 2013. Twenty-five patients with advanced lung cancer were evaluated by interventional pulmonology service for endobronchial stent placement for CAO. Eight patients did not require placement of a stent and 17 had obstructive lesions that required stenting by interventional pulmonology. RESULTS: Demographical parameters such as age and gender did not have a significant impact on the risk of hospitalization or OS of both groups of patients, however, those whose lesions did not mandate stent placement had significantly lower odds of hospitalization compared to patients with CAO requiring a stent (OR: 15.913, 95% CI: 1.211-209.068, P = 0.0352). Patients with advanced NSCLC and CAO that required stent placement had an OS of 13.9 m [3.9-19.9 m] compared to an OS of 23.9 m for patients with CAO not requiring a stent. We found out that patients with less severe CAO have lower odds of hospitalization and better OS compared to patients with CAO mandating stent placement. CONCLUSION: CAO patients with interventional pulmonology (IP) evaluation and management in addition, may have improved OS suggesting that IP consultation might offer both improvement in quality of life and overall survival to patients with advanced NSCLC and CAO. 
.

Exosomes as a Surrogate Marker for Autophagy in Peripheral Blood, Correlative Data from Phase I Study of Chloroquine in Combination with Carboplatin/Gemcitabine in Advanced Solid Tumors.

BACKGROUND: Autophagy is a catabolic process, utilized constitutionally by body cells to recycle nutrients and to remove unwanted/damaged intracellular constituents. It is enhanced during periods of stress, such as starvation and hypoxia, aiding in cell survival and it is linked to major cellular processes, such as apoptosis and antigen expression. The process has been extensively studied in vitro models or tumor tissue samples with rare application on human subjects. METHODS: Plasma samples from 24 advanced solid tumor patients were collected at different time points before and after chemotherapy. Their exosomes were isolate and blotted for microtubule-associated protein-1 light chain-3 (LC-3B) protein as a marker for autophagy. All the subjects received a standard chemotherapy regimen of carboplatin- gemcitabine with chloroquine (CQ)/ hydroxychloroquine (HCQ) in chronic doses throughout their treatment period as an autophagy modulator. CQ/HCQ was given in 50 mg increments as guided by their tolerability to treatment. RESULTS: A total of 267 plasma samples were obtained for the 24 patients and processed. Each sample corresponds to a single time point. The first group included 6 patients, all received 50 mg of CQ with chemotherapy. LC-3B I was detected in their isolated exosomes, while LC3-BII was not detected in their samples. The second cohort of patients included 3 subjects who re-ceived 100mg of HCQ. They demonstrated both LC3-BI and II on day 15 after chemotherapy in one patient, and on third cycle after 24 hours in the second patient. The third cohort included 3 subjects who received 150 mg of HCQ. All cases demonstrated LC3-BI and II on first cycle of treatment after less than 24 hours. The last cohort included 8 subjects, who received a fixed dose of 100 mg of HCQ with treatment. In this cohort, we were able to detect both LC3-B isoforms on advanced time points of second and third cycles. CONCLUSION: Detection of autophagy protein LC3-B in exosomes serves as a dynamic method to monitor autophagy. It can be utilized to study the effects of anti-neoplastic agents on autophagy and mechanisms of drug resistance, however, to standardize our results a larger specimen of patients should be included.

Papillary renal cell carcinoma: what is missing in research? A case report and a review of literature.

The incidence of renal cell carcinomas in adults ranges has been increasing over the past decades in both men and women. Once the incidence was 2.9%, now is reported to have increased to 3%-5% with male predominance according to the most recent reports of cancer statistics. The disease typically describes a group of different histopathological subtypes; the most common is clear cell carcinoma which accounts for 70%-80% of the diagnosed cases, while papillary renal cell carcinoma and chromophobe types represent 20% and 5%, respectively. In 1996, the renal cell carcinomas Heidelberg classification was introduced by Delahunt et al. It divides renal cell tumors into benign and malignant parenchymal neoplasms, excluding Wilm's tumor and secondary metastases and limiting each subcategory to the most commonly documented genetic abnormalities, if applicable. In this report, we discuss a case of metastatic type I papillary renal cell carcinoma treated with the anti-vascular endothelial growth factor receptor sunitinib and showing marked long-term clinical response. Through this case, we highlight the importance of re-classifying papillary renal cell carcinoma subtypes to prioritize the clinical management of these cases.

Retrospective Study of the Effect of Statins on the Outcome of Lung Cancer Patients, University of Cincinnati Experience.

Objectives: Numerous studies addressed the effect of statin on cancer patients. The aim of this study is to define the effect of statin administration with chemotherapy on the patients' outcomes. Methods: We retrospectively researched the database of the University of Cincinnati cancer to identify lung cancer patients who received statins (S+, n=41) during their treatment in our institute. We also, retrieved data for contemporaneously treated patients who did not receive statins (S-, n=159) as a control arm. Clinico-demographical data and overall survival (OS) were analyzed using Pearson's Chi-square (χ2) test and Kaplan-Meier survival curves with Log-rank test. Adjustment using Cox proportional hazard ratios (HR) were done based on (age, gender, race and stage) to identify effect of statins on their outcomes. Results: The median age for S+ was 64y (IQR; 55-69) and 71.2% of the patients were white. Histopathology was 55.4% and 31.7% for adenocarcinoma and squamous cell carcinoma, respectively. Fifty-six percent were stage IV in each study arm and the median OS was14.9 m. Median OS was insignificantly lower in S­ve arm (13.7 vs 15.6 months; P=0.652, HR=0.91, 95%CI 0.52-1.57). Our results show that after different types of adjustments, S+ did not show survival advantage (P>0.05) compared to the control arm. Conclusion: While showing an increase in overall survival in patients with advanced lung cancer, the results of this study did not reach statistical significance. This could be due for the small sample size of this retrospective study.

Myeloid Sarcoma.

Hematological malignancies can manifest as extramedullary soft tissue masses in relatively rare cases. The rarity of it causes a diagnostic and therapeutic challenge. One of the rarest manifestations is myeloid sarcoma (MS). MS develops as part of acute myeloid leukemia, myeloproliferative neoplasm, or myelodysplastic syndrome or at relapse, especially following allogeneic hematopoietic stem cell transplant. The tumor displays high myeloperoxidase expression, hence the color green, and is called chloroma. It most commonly appears in lymph nodes, skin and soft tissues, bone, testes, gastrointestinal tract, and peritoneum. Immunohistochemistry shows CD68-KP1 as the most commonly expressed marker, then myeloperoxidase, CD117, CD99, CD68/PG-M1, lysozyme, CD34, terminal deoxynucleotidyl transferase, CD56, CD61, CD30, glycophorin A, and CD4. Different chromosomal abnormalities including MLL rearrangement, t(8; 21), monosomy 7, trisomy 8, trisomy 11, trisomy 4, inversion (16), monosomy 16,16q deletion, 5q deletion, and 20q deletion were reported. Most of the literature about MS are case reports and small retrospective studies, thus there is limited clinical knowledge of the cases and their presentation and management plans. Here, we provide a review of what has been reported in the literature about MS in the light of our experiences.

Role of Targeted Therapy and Immune Checkpoint Blockers in Advanced Non-Small Cell Lung Cancer: A Review.

Advanced non-small cell lung cancer (NSCLC) is a complex disease comprising molecularly distinct tumor types, each with a unique biology that is becoming increasingly better characterized. The aim of this review is to present an optimized treatment schema and the accompanying diagnostic testing approach for patients with advanced NSCLC. There are a number of therapies currently approved for patients with advanced NSCLC, including agents that target particular oncogenic drivers, as well as immune checkpoint blockers (ICBs) that elicit an antitumor response. Identification of genetic alterations (e.g., epidermal growth factor receptor, anaplastic lymphoma kinase, reactive oxygen species proto-oncogene 1, B-Raf proto-oncogene) or programmed cell death ligand-1 expression levels in NSCLC requires diligent molecular testing at initial diagnosis and, in some cases, at disease progression to ensure the most efficacious treatment is delivered. Accurate molecular diagnostic testing, along with the careful selection of currently approved targeted agents, ICBs, or systemic chemotherapy, provides therapy that is personalized according to patients' needs to achieve the best possible outcome. Enrollment in clinical trials that further the development of tailored therapies is highly recommended at all stages of treatment. IMPLICATIONS FOR PRACTICE: Targeted therapies and immune checkpoint blockers provide effective and tailored options for patients with non-small cell lung cancer. Careful molecular analysis of tumor samples is necessary to identify the genetic alterations that are present, to ensure that each patient receives the most efficacious treatment for their specific tumor type. Personalized therapy provides each patient with the best probability for prolonged survival. Enrolling patients in clinical trials should be the first consideration before making each treatment decision.

Small or Non-Small Cell Lung Cancer Based Therapy for Treatment of Large Cell Neuroendocrine Cancer of The Lung? University of Cincinnati Experience.

Large cell neuroendocrine cancer (LCNEC) of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinomas. No defined optimal therapy has been described for this subset of patients and the question of whether these patients should be treated with non-small cell lung cancer (NSCLC) treatment protocols, according to the National Comprehensive Cancer Network (NCCN) guidelines, or with small cell lung cancer (SCLC) due to histological and clinical similarities is still uncertain. We conducted a retrospective review of patients identified with diagnosis of LCNEC of the lung at the University of Cincinnati Cancer Center from the year 2002 to 2012 to determine which treatment approach resulted in improved outcomes in this rare category of disease. Patients who received chemotherapy whether NSCLC (group A) or SCLC (group B) protocols did not show significant changes in OS (P=0.911). Meanwhile, patients who underwent surgery (group C) had better OS compared to groups A and B (P= 0.027 and 0.024, respectively). This analysis reveals that outcomes for SCLC or NSCLC treatment strategies in LCNEC patients did not result in survival advantages and future research should be addressing it as a separate entity.

Clinical Presentation and Treatment Options for Clear Cell Lung Cancer: University of Cincinnati A Case Series and Literature Review of Clear Cell Lung Cancer

Clear cell carcinomas are common finding in renal, ovarian and uterine carcinomas. However, clear cell lung cancer (CCLC), first described by Liebow and Castleman in 1963, is considered an extremely rare variant of lung tumors. The 2011 WHO classification of lung tumors considered CCLC as a rare cytologic feature of squamous cell or adenocarcinomas. It is no longer recognized as a formal subtype, albeit it can be referred to in the pathological diagnosis as "with clear cell features" even with marginal fractions of the tumor cells. Such recognition is needed since the variation in clinical features and outcome in this subset of patients. The disease has a clinically vague natural history, is characterized by slight female predominance and is often seen in the elderly. As frequently encountered with rare diseases, its clinical course and treatment options have many questions still yet to be answered. In this paper, we review both the natural history and treatment options mentioned in literature, in the light of our experience by reporting a case series of four patients diagnosed with CCLC and highlight their aspects.

GNQ-209P Mutation in Metastatic Uveal Melanoma and Treatment Outcome.

Metastatic prognosis in uveal melanoma is assessed by gene expression profiling (GEP) testing of the tumor cells, usually obtained by fine needle aspiration (FNA). GEP has demonstrated high accuracy in distinguishing class I and II tumors, both having different metastatic potential. Transcriptomic studies identified distinct mutations including somatic mutations in GNAQ and GNA11, detected in more than 80%, and contribute to the upregulation of the mitogen-activated protein kinase (MAPK) pathway and the development of uveal melanoma (UM). The role of these mutations in treatment selection and possible benefit from targeted therapy are somewhat unclear. However, until the discovery of novel agents, local versus systemic therapies remain options for treatment that can still be considered for disease control in certain cases. We report a series of patients with metastatic UM with distinct mutational profiles. One had significant liver metastases with proven GNQ-209P mutation on tissue biopsy while peripheral blood molecular profiling did not show these mutations. The other three cases had no GNQ-209P mutation. All cases received nab-paclitaxel (Abraxane) as a treatment drug, and we record their responses to treatment and their molecular-profiling results.

Systemic Chemotherapy for Progression of Brain Metastases in Extensive-Stage Small Cell Lung Cancer.

Lung cancer is the most common cause of cancer related mortality in men and women. Approximately 15% of lung cancers are small cell type. Chemotherapy and radiation are the mainstay treatments. Currently, the standard chemotherapy regimen includes platinum/etoposide. For extensive small cell lung cancer, irinotecan and cisplatin have also been used. Patients with relapsed small cell lung cancer have a very poor prognosis, and the morbidity increases with brain metastases. Approximately 10%-14% of small cell lung cancer patients exhibit brain metastases at the time of diagnosis, which increases to 50%-80% as the disease progresses. Mean survival with brain metastases is reported to be less than six months, thus calling for improved regimens. Here we present a case series of patients treated with irinotecan for progressive brain metastases in small cell lung cancer, which serves as a reminder of the role of systemic chemotherapy in this setting.

Male pelvic squamous cell carcinoma of unknown primary origin.

Pelvic squamous cell carcinoma of unknown primary origin has been described in several case reports of female patients. However, there have been no published reports describing male patients with pelvic squamous cell cancer of unknown primary origin. Our case describes a 52-year-old man who presented with right buttock pain, rectal urgency, and constipation. His physical examination demonstrated tenderness to palpation around his gluteal folds. Computed tomography scan of his abdomen and pelvis demonstrated a large mass in his retroperitoneum. The mass was determined to be squamous cell carcinoma of unknown primary origin. Additionally, the patient had small nodules in his right lower lung lobe and right hepatic lobe. The patient was treated with concomitant chemoradiation, including cisplatin and intensity-modulated radiation therapy, followed by carboplatin and paclitaxel. The patient achieved partial remission, in which he remained one year after his presentation. Our case is consistent with the literature which suggests that squamous cell carcinoma of unknown primary origin occurring outside of the head and neck region may have a more favorable prognosis than other carcinomas of unknown primary origin. Further studies are necessary to determine the most appropriate work-up, diagnosis, and optimal treatment strategies.

Bilateral choroidal metastasis from non-small cell lung cancer.

Breast and lung cancers are the most common primary neoplasms to manifest with choroidal metastases. The incidence of choroidal metastases from metastatic lung cancer was reported to be 2-6.7%. We report a case of bilateral choroidal metastasis from non-small cell lung cancer. A 59-year-old Caucasian female patient, never a smoker, was diagnosed with stage IV lung adenocarcinoma metastatic to the pleura, bones, and the brain. Her initial scan of the chest showed innumerable soft tissue nodules and mediastinal adenopathy compatible with metastatic disease. Her initial brain MRI showed numerous small enhancing lesions consistent with extensive disease. Unfortunately, during her follow-up visits, she presented with bulge on her left eye. Simultaneously, her follow-up chest scan showed increase in the size of the lung nodules. She continued to have a reasonable performance status at that time, except for mild increase in her dyspnea. The choroidal metastases require a multidisciplinary care and should be among the differential patients with malignancy who present with ocular symptoms.

Benign metastasizing leiomyoma: a rare type of lung metastases-two case reports and review of the literature.

Benign metastasizing leiomyoma (BML) is a rare disease that usually occurs in women of reproductive age. They typically have history of uterine leiomyoma treated with hysterectomy. BML can metastasize to distant organs, with the lung being the most common organ. We report two patients who presented with benign metastasizing leiomyoma to the lung. Our first case was a fifty-two-year-old female who presented with multiple lung masses, with a past medical history of uterine leiomyoma who underwent hysterectomy 17 years ago. A CT-guided biopsy showed benign appearing spindle cells and pathology confirmed her diagnosis with additional positive estrogen/progesterone receptor stains. Our second case was a fifty-six-year-old female who presented with multiple cavitary pulmonary nodules. She subsequently underwent a video-assisted thoracoscopic surgery (VATS) with wedge resection of one of the nodules. Pathology confirmed the diagnosis based on morphology and immunohistochemical staining strongly positive for estrogen/progesterone receptors. Benign metastasizing leiomyoma is a rare condition which may affect women of reproductive age. This should be considered in the differential in patients who present with multiple pulmonary nodules, especially with a history of uterine leiomyoma. Additional stains, such as estrogen/progesterone receptors, may need to be done to confirm the diagnosis.

Thyroid metastasis from nonsmall cell lung cancer.

Background. Thyroid metastases are rare. Clinically, they represent less than 4% of thyroid malignancy in clinical studies. Aim. To assess various presentations and therapy for patients with lung cancer metastatic in the thyroid. Materials and Methods. We report a case of metastatic adenocarcinoma of the lung to the thyroid. We reviewed similar reports through PubmMed search from 1997 until 2013. Case Presentation. A 48-year-old lady was seen in the clinic for an adenocarcinoma of left upper lobe (LUL) of the lung; she received neoadjuvant chemotherapy then LUL lobectomy. After 9 months she presented with diffuse goiter initially believed to be a solitary metastatic lesion as it was positive for adenocarcinoma of lung origin on histopathological exam with TTF-1 positivity. Unfortunately, PET scan showed additional mediastinal lymphadenopathy. Conclusion. The treatment strategy for metastatic thyroid disease is based on a multidisciplinary approach, where thyroidectomy would have been considered in case of a solitary metastatic involvement, but further metastatic workup is mandated to direct further systemic therapy versus palliative radiation therapy.