Lukman Tijani

Immunological treatment options for locoregionally advanced head and neck squamous cell carcinoma.

Patients with squamous cell carcinoma of the head and neck (HNSCC) are usually treated by a multimodal approach with surgery and/or radiochemotherapy as the mainstay of local–regional treatment in cases with advanced disease. Both chemotherapy and radiation therapy have the disadvantage of causing severe side effects, while the clinical outcome of patients diagnosed with HNSCC has remained essentially unchanged over the last decade. The potential of immunotherapy is still largely unexplored. Here the authors review the current status of the art and discuss the future challenges in HNSCC treatment and prevention.

Perspective for prophylaxis and treatment of cervical cancer: an immunological approach.

As the second most common cause of cancer-related death in women, human papilloma virus (HPV) vaccines have been a major step in decreasing the morbidity and mortality associated with cervical cancer. An estimated 490,000 women are diagnosed with cervical cancer each year. Increasing knowledge of the HPV role in the etiology of cervical cancer has led to the development and introduction of HPV-based vaccines for active immunotherapy of cervical cancer. Immunotherapies directed at preventing HPV-persistent infections. These vaccines are already accessible for prophylaxis and in the near future, they will be available for the treatment of preexisting HPV-related neoplastic lesions.

A Prospective Pilot Study of Single 19 Gy Fraction High-Dose-Rate Brachytherapy for Favorable-Risk Adenocarcinoma of the Prostate

Objective: To evaluate the acute genitourinary (GU) and gastrointestinal (GI) toxicities, health-related quality of life (HRQOL) factors, biochemical control rates, and technical feasibility of high-dose-rate (HDR) brachytherapy as monotherapy for prostate cancer delivered in a single fraction. Methods: A single-institution, prospective pilot study evaluating 6 patients with low- and intermediate-risk prostate cancer treated in 2013. Patients received a single 19 Gy fraction as HDR monotherapy. Patients were assessed according to the Common Terminology Criteria for Adverse Events version 4.0, the International Index of Erectile Function (IIEF-5), the International Prostate Symptom Score (IPSS), the Expanded Prostate Cancer Index Composite–Bowel Assessment (EPIC-Bowel), a Quality of Life (QOL) Assessment, and an institutionally designed quality of care (QOC) questionnaire. Biochemical failure was defined as a prostate-specific antigen (PSA) nadir plus 2 ng/ml. Results: Patients tolerated the implant well and were all discharged home the same day by approximately 4 pm. Median follow-up was 9 months. No grade 3, 4 or 5 toxicities were observed. Two of the 6 patients (33%) experienced grade 2 GU toxicity. One patient (17%) experienced grade 2 GI toxicity. HRQOL bowel and urinary assessments revealed a majority of complaints at 3 months, which returned to baseline at 6 months. Conclusion: HDR brachytherapy as monotherapy for favorable-risk prostate cancer using one implant delivered in a single 19 Gy dose has acceptable acute toxicities and HRQOL reports similar to alternative treatment options.

A Systematic Review and Meta-Analysis of Randomized Controlled Trials to Evaluate the Risk of Hematological Toxicities in Patients with Multiple Myeloma Treated with Daratumumab

S242 p 1⁄4 0.70); asthenia, 0.84 (95% CI: 0.38 e 1.85, p 1⁄4 0.66); and insomnia, 1.05 (95% CI: 0.80 e 1.36; p 1⁄4 0.71). The RR of highgrade adverse effects were as follows: nausea, 1.92 (95% CI: 0.17 e 21.60; p 1⁄4 0.59); diarrhea, 1.43 (95% CI: 0.75 e 2.74, p 1⁄4 0.27); fatigue, 1.87 (95% CI: 0.99 e 3.52; p 1⁄4 0.051); asthenia, 0.81 (95% CI: 0.30 e 2.14, p 1⁄4 0.67); and insomnia, 0.30 (95% CI: 0.04 e 1.93; p 1⁄4 0.20). Conclusions: Addition of daratumumab did not increase the risk of gastrointestinal toxicities and healthrelated quality of life events in patients with multiple myeloma compared to control arm, while contributing substantial survival benefits.

Coal worker’s pneumoconiosis and sarcoid-like reaction mimicking lymph node metastases in a patient with lung cancer: A case report

Sarcoid-like reactions occur in a small percentage of cancer patients. This reaction causes lymph nodes to appear hypermetabolic when viewed with Fludeoxyglucose-Positron Emission Tomography (FDG-PET). This is clinically important, because it could be confused with tumor metastasis and could affect the staging and treatment of the cancer. In addition to sarcoid-like reactions and metastasis, several other disease processes can cause lymph nodes to appear hypermetabolic with FDG-PET, including coal worker’s pneumoconiosis. We present the case of a 61-year-old coal miner who was diagnosed with lung cancer. FDG-PET showed increased uptake in ipsilateral and contralateral mediastinal lymph. The patient had bronchoscopy with endobronchial ultrasound (EBUS) guided biopsy of the mass and needle aspiration of bilateral lymph nodes of the mediastinum. All the biopsies were negative. The patient then had a left upper lobectomy and left mediastinal lymph node dissection. The PET findings were originally attributed to metastasis of the tumor, but pathology of the ipsilateral nodes showed silicotic changes due to pneumoconiosis and non-caseating granulomas from a sarcoid-like reaction. Because the ipsilateral lymph nodes had no evidence of metastasis and EBUS biopsy of the contralateral nodes was negative, it was unlikely that the changes in the contralateral nodes were due to metastasis, and no adjuvant treatment was offered. At more than one year after surgery, the patient remains stable with no evidence of recurrence, and we have clinical assurance that the changes in the lymph nodes were due to the sarcoid-like reaction and pneumoconiosis and not metastasis. FDG-PET is useful for detection of lung cancer, but pathology is necessary for staging and determining treatment for the patient.

PS01.34: Differential Modulation of Glutathione Metabolism in Adeno and Squamous NSCLC by 2HF: Topic: Medical Oncology

eliminate false positives, secondary negative screening was performed using H3118 cells that were stably transfected with CRE (CREB responsive element) containing the same luciferase vector backbone. The effects of potential NR4A2 promoter inhibitors were further validated using several lung cancer cell lines. Status of NR4A2 and a downstream gene, osteopontin (OPN) expression in these cell lines were determined by western blotting and RT-PCR. Since multiple EGFR tyrosine kinase inhibitors (EGFR-TKIs) were identified by the screening, inhibitors of downstream molecules such as RAF, MEK, PI3K, were then used to determine if they can influence NR4A2 signaling. Results: Among positive hits, 23 FDA and 43 Life chemicals had a known mechanism of action. Three EGFR-TKIs and one Src inhibitor were included and then further analyzed.. These drugs inhibited H3118 cell growth in vitro, and led to depression of phospho-ERK, NR4A2 and OPN protein levels, indicating these indirectly regulate NR4A2 by suppression of upstream pathway. Inhibitors of other EGFR downstream pathway such as RAF, PI3K, STAT3, did not affect cell proliferation or NR4A2/OPN protein expression. NR4A2 negative H2087 cells were not sensitive to EGFR/Src inhibitors as compared to H3118. Conclusion: Our HTS screening showed several EGFR and Src inhibitors can indirectly regulate NR4A2 by suppression of upstream signaling, suggesting a new mechanism where EGFR WT cancer cells can be addicted to EGFR-TKIs. Further research to confirm the findings are warranted. Positive hit compounds with unknown mechanism of action are also under investigation.

Abstract 3440: High-dose-rate brachytherapy as monotherapy for favorable-risk adenocarcinoma of the prostate delivered in a single 19 Gy fraction: Preliminary results of a prospective pilot study

INTRODUCTION: We evaluated the acute genitourinary (GU) and gastrointestinal (GI) toxicities, health-related quality of life (HRQOL) factors, biochemical control rates, and technical feasibility of high-dose-rate (HDR) brachytherapy as monotherapy for favorable-risk prostate cancer delivered in a single 19 Gy fraction. METHODS: A single-institution, prospective pilot study was performed by evaluating 6 patients with low- and intermediate-risk prostate cancer treated with high-dose-rate (HDR) brachytherapy as monotherapy. Patients received a single 19 Gy fraction as HDR monotherapy without the use of a transperineal hyaluronic acid injection. Patients were assessed according to the Common Terminology Criteria for Adverse Events version 4.0 and Health-Related Quality of Life (HRQOL) questionnaires. Additionally, prostate specific antigen levels have been followed for evidence of biochemical failure. RESULTS: All 6 patients tolerated the implant well and were all discharged home the same day. Median follow-up was 15 months with all subjects followed for at least 12 months. No grade 3, 4, or 5 toxicities were observed. Two of the 6 patients experienced grade 2 GU toxicity. One patient experienced grade 2 GI toxicity. HRQOL bowel and urinary assessments revealed peak complaints at 3 months which returned to baseline at 6 months. There have been no biochemical relapses. CONCLUSION: This is the first study using HDR brachytherapy as monotherapy for favorable-risk prostate cancer using one implant delivered in a single 19 Gy dose in the United States. All patients demonstrated acceptable acute toxicities and were pleased with their cost-effective treatment choice. Citation Format: Scott Dahlbeck, Chase C. Hansen, Werner deRiese, A. Robert Kagan, Carlos Torres, Maurizio Chiriva-Internati, Everardo Cobos, Jose A. Figueroa, Diane Nguyen, Lukman Tijani, Jaden D. Evans. High-dose-rate brachytherapy as monotherapy for favorable-risk adenocarcinoma of the prostate delivered in a single 19 Gy fraction: Preliminary results of a prospective pilot study. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3440. doi:10.1158/1538-7445.AM2015-3440

Reversal of liver function without exchange transfusion in sickle cell intrahepatic cholestasis

Sickle cell intrahepatic cholestasis (SCIC) is a rare but fatal complication of sickle cell disease. It is found mainly in homozygous sickle cell disease. To date, there are no standard diagnostic criteria or well-established therapeutic approaches to this condition. Herein, we report this case of a 48-year-old man with sickle cell anemia and a total bilirubin of 78.5 mg/dL without evidence of extrahepatic biliary obstruction or viral hepatitis. The patient had a hemoglobin S level of 87.9%, acute renal failure, and mild coagulopathy. Despite the disease severity, he refused exchange transfusion (ET) with packed red blood cells. He was transfused with 2 units of blood and treated mainly with supportive measures. His total bilirubin levels trended down to normal days after discharge. Multiple studies have shown a significant decrease in the mortality rate in SCIC after ET. To date, only two reported adult cases have survived SCIC without aggressive treatment. Our case is the third case that demonstrates recovery of severe SCIC without ET.