Nagla Abdel Karim

Influenza Vaccination in Cancer Patients Undergoing Systemic Therapy

Background Cancer patients often experience preventable infections, including influenza A and B. These infections can be a cause of significant morbidity and mortality. The increased risk of infection may be because of either cancer itself or treatment-induced immunosuppression. 1 Influenza immunization has been shown to decrease the risk of influenza infection in patients with intact immunity. 2 In cancer patients, active immunization has been shown to confer protective immunity against several infections at similar rates to healthy individuals, which has translated into decreased duration and severity of infection and potentially improved morbidity and mortality. 3 Objectives 1. To assess the efficacy of influenza vaccination in stimulating immunological response in patients with cancer during chemotherapy compared to control groups. 2. To assess the efficacy of influenza vaccination in preventing confirmed influenza and influenza-like illness and/or stimulating immunological response in children with cancer treated with chemotherapy, compared to placebo, no intervention, or different dosage schedules. 3. To determine the adverse effects associated with influenza vaccination in patients with cancer. Search Methods We searched MEDLINE/PubMed database for articles published from 1964 to 2013 using the search terms “cancer,” “adult,” “influenza vaccination,” and “chemotherapy.” Selection Criteria We included studies based on systematic sampling with defined clinical criteria irrespective of the vaccination status of cancer patients. Studies measure the serological response or clinical response to compare between the study group and the control group. Studies assessed the inactivated influenza vaccines and live attenuated influenza vaccine (LAIV) protective serological reaction and the clinical outcomes after vaccination. Data Collection and Analysis Two independent authors assessed the methodological quality of included studies and extracted data. Main Results We included 16 studies (total number of participants = 1,076). None of the included studies reported clinical outcomes. All included studies reported on influenza immunity and adverse reaction on vaccination. We included 6 solid tumor studies and 10 hematological studies. In 12 studies, the serological response to influenza vaccine was compared in patients receiving chemotherapy (n = 425) versus those not receiving chemotherapy (n = 376). In three studies, the serological responses to influenza vaccination in patients receiving chemotherapy are compared to that in healthy adult. Measures used to assess the serological responses included a four-fold rise increase in antibody titer development of hemagglutination inhibition (HI) titer >40, and pre- and post-vaccination geometric mean titers (GMTs). Immune responses in patients receiving chemotherapy were consistently weaker (four-fold rise of 17–52%) than in those who had completed chemotherapy (50–83%) and healthy patients (67–100%). Concerning adverse effects, oncology patients received influenza vaccine, and the side effects described were mild local reactions and low-grade fever. No life-threatening or persistent adverse effects were reported. Authors’ Conclusion Patients with solid and some of hematological tumors are able to mount a serological response to influenza vaccine, but it remains unclear how much this response protects them from influenza infection or its complications. Meanwhile, influenza vaccine appears to be safe in these patients. While waiting results of randomized controlled trials to give us more details about the clinical benefits of the influenza vaccination, the clinicians should consider the currently proved benefits of influenza vaccination on management of the cancer patients undergoing systematic chemotherapy such as decrease in the duration and severity of the of the disease, and significant decrease in influenza-associated morbidity and mortality in these high-risk patients. 3

Pulmonary Sarcomatoid Carcinomas Commonly Harbor Either Potentially Targetable Genomic Alterations or High Tumor Mutational Burden as Observed by Comprehensive Genomic Profiling

Introduction: Pulmonary sarcomatoid carcinoma (PSC) is a high‐grade NSCLC characterized by poor prognosis and resistance to chemotherapy. Development of targeted therapeutic strategies for PSC has been hampered because of limited and inconsistent molecular characterization. Methods: Hybrid capture–based comprehensive genomic profiling was performed on DNA from formalin‐fixed paraffin‐embedded sections of 15,867 NSCLCs, including 125 PSCs (0.8%). Tumor mutational burden (TMB) was calculated from 1.11 megabases (Mb) of sequenced DNA. Results: The median age of the patients with PSC was 67 years (range 32–87), 58% were male, and 78% had stage IV disease. Tumor protein p53 gene (TP53) genomic alterations (GAs) were identified in 74% of cases, which had genomics distinct from TP53 wild‐type cases, and 62% featured a GA in KRAS (34%) or one of seven genes currently recommended for testing in the National Comprehensive Cancer Network NSCLC guidelines, including the following: hepatocyte growth factor receptor gene (MET) (13.6%), EGFR (8.8%), BRAF (7.2%), erb‐b2 receptor tyrosine kinase 2 gene (HER2) (1.6%), and ret proto‐oncogene (RET) (0.8%). MET exon 14 alterations were enriched in PSC (12%) compared with non‐PSC NSCLCs (˜3%) (p < 0.0001) and were more prevalent in PSC cases with an adenocarcinoma component. The fraction of PSC with a high TMB (>20 mutations per Mb) was notably higher than in non‐PSC NSCLC (20% versus 14%, p = 0.056). Of nine patients with PSC treated with targeted or immunotherapies, three had partial responses and three had stable disease. Conclusion: Potentially targetable GAs in National Comprehensive Cancer Network NSCLC genes (30%) or intermediate or high TMB (43%, >10 mutations per Mb) were identified in most of the PSC cases. Thus, the use of comprehensive genomic profiling in clinical care may provide important treatment options for a historically poorly characterized and difficult to treat disease.

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.

Mucoepidermoid Carcinoma of the Lung: A Case Report and Literature Review

Introduction. Mucoepidermoid carcinoma (MEC) of the lung is a rare form of lung cancer that is classified into low grade and high grade based on histological features. Surgical resection is the primary treatment for low-grade MEC with excellent outcomes, while high-grade MEC is a more aggressive form of malignancy. Clinical Case. We report a case of a 46-year-old woman who presented with dyspnea on exertion. Imaging studies revealed a mass involving the right upper lobe bronchus. Bronchoscopy, surgical resection, and pathological examination revealed a low-grade MEC with tumor-free margins. No adjuvant treatment was given. Discussion. Primary pulmonary MEC is a rare type of lung cancer with only few reported cases. This patient illustrates a typical presentation for low-grade MEC wherein surgical resection is considered curative. In contrast, high-grade MEC is a more aggressive malignancy with a poorer outcome. The role of targeted therapy directed against EGFR or a novel CRTC1-MAML2 fusion protein expressed in some high-grade tumors is yet to be determined.

Frontline Systemic Therapy With Pemetrexed-Platinum in Nonsquamous Non-Small-Cell Lung Cancer With Asymptomatic Brain Metastases.

The incidence of brain metastases from nonsquamous non–small-lung cancer is increasing as a result of superior imaging techniques for early detection of distant metastases. Although whole-brain radiation therapy and stereotactic radiosurgery along with systemic chemotherapy have shown to be effective in alleviating symptoms and improving outcomes, the approach to patients with asymptomatic brain metastases remains elusive. We explored the literature for a possible role of frontline systemic chemotherapy in asymptomatic brain metastases from nonsquamous non–small-lung cancer and found promising evidence that upfront systemic therapy with pemetrexed–platinum regimens might be a reasonable option for these patients and would forestall the need for upfront brain radiation therapy. More large-scale phase II and phase III clinical trials are needed to further investigate the frontline use of pemetrexed–platinum regimens 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.

Prolonged Survival in a Patient with Metastatic Vasoactive Intestinal Peptide Producing Pancreatic Neuroendocrine Tumors

VIPomas are rare neuroendocrine tumors that secrete vasoactive intestinal peptide. They are detected in 1 in ten million people per year. The majority of these tumors arises within the pancreas, but may also arise as other VIP-secreting tumors as in bronchogenic carcinoma, colon carcinoma, ganglioneuroblastoma, pheochromocytoma, hepatoma and adrenal tumors. They are characterized by profound diarrhea, hypokalemia, and achlorhydria and were first described by Verner and Morrison in 1958. It was also named pancreatic cholera as the cholera toxin acts; the Vasoactive Intestinal Peptide (VIP) causes elevation of the cyclic adenosine monophosphate, resulting in intestinal smooth muscle relaxation, inhibition of electrolyte absorption and profound secretory diarrhea. We are reporting a case involving a 42 year old male patient who presented with intermittent attacks of watery diarrhea up to 10 times per day for 3 weeks mostly worsening in the last 3 days prior to seeking medical advice. Stool studies were negative, but patient had hyperglycemia and mild hyponatremia. Further evaluation revealed a pancreatic mass with multiple hepatic focal lesions encountered in abdominal ultrasound and CT scan. Ultrasound guided biopsy revealed metastatic pancreatic endocrine carcinoma with VIP expression. Serum VIP level was elevated to 496 (Normal <100). We report a case of metastatic well-differentiated VIPoma treated mainly with long acting octreotide and streptozocin/5fluorouracil combination showing marked improvement of symptoms, minimal response of the tumor size but more significantly, more than 2 year period survival/follow up in a patient that was not a candidate for surgical resection. Review of literature focused on cases with metastatic VIPoma who were not surgical candidates, but had prolonged survival of more than 2 years disease. We reviewed the different therapeutic options offered for this patient population exploring the response rates, survival and recent recommendations.

Pulmonary sarcomatoid carcinoma: university of cincinnati experience

Objectives To review the outcomes of treatment in patients with pulmonary sarcomatoid carcinoma (PSC) treated at the University of Cincinnati Medical Center (UCMC). Results There was no significant difference in survival of patients treated with chemotherapy alone (median, 256 days) compared to patients not undergoing treatment (median, 205.5 days). Patients who underwent surgery and adjuvant chemotherapy showed a trend in improvement of survival (median, 457.6 days). Patients requiring only surgery had the longest OS of 713.5 days. Conclusions Systemic chemotherapy alone did not improve survival in patients with PSC. Surgery provides the greatest overall survival benefit and adjuvant chemotherapy may also improve survival. Methods From 2000 to 2014, twenty-five patients with pathologically confirmed PSC were treated at UCMC. The outcomes were retrospectively analyzed by treatment with overall survival (OS) as the endpoint.

The use of pharmacogenomics for selection of therapy in non-small-cell lung cancer.

Introduction Performance status (PS) is the only known clinical predictor of outcome in patients with advanced non-small-cell lung cancer (NSCLC), although pharmacogenomic markers may also correlate with outcome. The aim of our study was to correlate clinical and pharmacogenomic measures with overall survival. Methods This was an IRB approved, retrospective study in which the medical records of 50 patients with advanced NSCLC from 1998–2008 were reviewed, and gender, race, PS, and chemotherapy regimens were documented. Stromal expression of pharmacogenomic markers (VEGFR, ERCC1, 14-3-3σ, pAKT, and PTEN) was measured. Clinical factors and pharmacogenomics markers were compared to overall survival using a Cox proportional hazards model. Results Forty patients received platinum-based therapy. Median age was 65 years. Improved PS, female gender, and gemcitabine therapy were significantly associated with longer overall survival (P = 0.004, P = 0.04, and P = 0.003, respectively). Age was not associated with survival. Caucasians had better overall survival in comparison to African Americans with median survival of 14.8 months versus 10.4 months (P = 0.1). Patients treated with platinum-based therapy had better survival of 15 months versus 8 months for non-platinum based therapy (P = 0.01). There was no significant association between any of the pharmacogenomics markers and overall survival other than in patients treated with platinum, in whom ERCC1 negativity was strongly associated with longer survival (P = 0.007). Conclusion ERCC1 negativity with platinum therapy, gemcitabine therapy, good PS, and female gender all correlated with improved overall survival in patients with advanced NSCLC.

Phase II Clinical Trial of Gefitinib for the Treatment of Chemonaïve Patients with Advanced Non-small Cell Lung Cancer with Poor Performance Status

Background Patients with advanced non-small cell lung cancer (NSCLC) have no curative treatment options; therefore, improving their quality of life (QOL) is an important goal. Gefitinib, an epidermal growth factor receptor (EGFR) inhibitor, is a safe oral agent that may be of benefit to a specific population of NSCLC. Patients and Methods A Phase II clinical trial included chemonaïve patients with advanced NSCLC and poor performance status (PS). Response rate, progression-free survival, overall survival, QOL using the Functional Assessment of Cancer Therapy – Lung (FACT-L) questionnaire, and Trial Outcome Index (TOI) were evaluated. Results Twelve out of 19 enrolled patients were evaluable. The median age for the evaluable patients was 68.8 years (59.7–74.6). Out of all the patients, 7 (58.3%) had adenocarcinoma and 5 (41.7%) had squamous cell carcinoma. The median duration of treatment was 62.5 days (26.5–115.0) in the evaluable patients. Grade 3/4 toxicities included fatigue, rash, diarrhea, and nausea. One patient had partial response, eight patients had stable disease (SD), and three patients progressed. The median overall survival for the evaluable population was 4.9 months (2.3–16). The median progression-free survival was 3.7 months (1.9–6.6). TOI was marginally associated with the overall survival, with a hazard ratio of 0.92 (95% confidence interval: 0.84, 1.0) (P = 0.061). FACT-L score and the TOI were highly correlated (r = 0.96, P < 0.0001). TOI scores were higher in African Americans compared to Caucasians and increased with age. Conclusion Our results suggest that gefitinib use in patients with NSCLC and poor PS may improve the QOL of older patients and African American patients.