Z.S. Buchwald

Matrix metalloproteinases: Their functional role in lung cancer

Lung malignancy is the foremost cause of cancer-related deaths globally and is frequently related to long-term tobacco smoking. Recent studies reveal that the expression of matrix metalloproteinases (MMPs) is extremely high in lung tumors compared with non-malignant lung tissue. MMPs are zinc-dependent proteases and are involved in the degradation of extracellular matrix (ECM). Several investigations have shown that MMPs manipulate the activity of non-ECM molecules, including cytokines, growth factors and receptors that control the tumor microenvironment. In this review, we have summarized and critically reviewed the published works on the role of MMPs in non-small-cell lung cancer. We have also explored the structure of MMPs, their various types and roles in lung cancer metastasis including invasion, migration and angiogenesis.

Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: An analysis of the National Cancer Data Base: Chemotherapy vs Chemotherapy and Radiation

The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high‐risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high‐risk grade 2 gliomas treated with CA versus CRT.

Exosomes, Their Biogenesis and Role in Inter-Cellular Communication, Tumor Microenvironment and Cancer Immunotherapy

Exosomes are extracellular vesicles ranging from 30 to 150 nm in diameter that contain molecular constituents of their host cells. They are released from different types of cells ranging from immune to tumor cells and play an important role in intercellular communication. Exosomes can be manipulated by altering their host cells and can be loaded with products of interest such as specific drugs, proteins, DNA and RNA species. Due to their small size and the unique composition of their lipid bilayer, exosomes are capable of reaching different cell types where they alter the pathophysiological conditions of the recipient cells. There is growing evidence that exosomes are used as vehicles that can modulate the immune system and play an important role in cancer progression. The cross communication between the tumors and the cells of the immune system has gained attention in various immunotherapeutic approaches for several cancer types. In this review, we discuss the exosome biogenesis, their role in inter-cellular communication, and their capacity to modulate the immune system as a part of future cancer immunotherapeutic approaches and their potential to serve as biomarkers of therapy response.

Increase in PD-L1 expression after pre-operative radiotherapy for soft tissue sarcoma

ABSTRACT Soft tissue sarcomas (STS) have minimal expression of PD-L1, a biomarker for PD-1 therapy efficacy. Radiotherapy (RT) has been shown to increase PD-L1 expression pre-clinically. We examined the expression of PD-L1, pre- and post-RT, in 46 Stage II-III STS patients treated with pre-operative RT (50–50.4 Gy in 25–28 fractions) followed by resection. Five additional patients who did not receive RT were utilized as controls. PD-L1 expression on biopsy and resection samples was evaluated by immunochemistry using the anti PD-L1 monoclonal antibody (E1L3 N clone; Cell Signaling). Greater than 1% membranous staining was considered positive PD-L1 expression. Changes in PD-L1 expression were analyzed via the Fisher exact test. Kaplan-Meier statistics were used to correlate PD-L1 expression to distant metastases (DM) rate. The majority of STS were T2b (87.0%), high-grade (80.4%), undifferentiated pleomorphic histology (71.7%), and originated from the extremities (84.6%). Zero patients demonstrated PD-L1 tumor expression pre-RT. Post-RT, 5 patients (10.9%) demonstrated PD-L1 tumor expression (p = 0.056). Tumor associated macrophages (TAM) expression of PD-L1 increased after RT: 15.2% to 45.7% (p = 0.003). Samples from controls demonstrated no baseline (0%) or change in tumor PD-L1 expression. Freedom from DM was lower for patients with PD-L1 TAM expression post-RT (3 years: 49.7% vs. 87.8%, log-rank p = 0.006); TAM PD-L1 positivity remained an independent predictor for DM on multivariate analyses (Hazard ratio – 0.16, 95% confidence interval: 0.034–0.721, p = 0.042). PD-L1 expression on human STS tumor and TAM appears to elevate after pre-operative RT. Expression of PD-L1 on TAM after RT was associated with a higher rate of DM.

Angiotensin receptor blockade: a novel approach for symptomatic radiation necrosis after stereotactic radiosurgery

Preclinical evidence suggests angiotensin blockade therapy (ABT) decreases late radiation toxicities. This study aims to investigate the association between ABT and symptomatic radiation necrosis (SRN) following stereotactic radiosurgery (SRS). Resected brain metastases (rBM) and arteriovenous malformation (AVM) patients treated with SRS from 2002 to 2015 were identified. Patients in the ABT cohort were on therapy during SRS and at 1-month follow up. Kaplan Meier method and cumulative incidence model were used to analyze overall survival (OS) and intracranial outcomes. 228 consecutive patients were treated with SRS: 111 with rBM and 117 with AVM. Overall, 51 (22.4%) patients were in the ABT group: 32 (28.8%) in the rBM and 19 (16.2%) in AVM cohorts. Baseline characteristics were similar, except for higher Graded Prognostic Analysis (3–4) in the rBM (ABT: 25.0% vs. non-ABT: 49.0%, p = 0.033) and median age in the AVM (ABT: 51.4 vs. non-ABT: 35.4, p < 0.001) cohorts. In both populations, OS and intracranial efficacy (rBM—local control; AVM—obliteration rates) were statistically similar between the cohorts. ABT was associated with lower 1-year SRN rates in both populations: rBM, 3.1 versus 25.3% (p = 0.003); AVM, 6.7 vs. 14.6% (p = 0.063). On multivariate analysis, ABT was a significant predictive factor for rBM (HR: 0.17; 95% CI 0.03–0.88, p = 0.035), but did not reach statistical significance for AVM (HR: 0.36; 95% CI 0.09–1.52, p = 0.165). ABT use appears to be associated with a reduced risk of SRN following SRS, without detriment to OS or intracranial efficacy. A prospective trial to validate these findings is warranted.

Post-treatment neutrophil-to-lymphocyte ratio predicts for overall survival in brain metastases treated with stereotactic radiosurgery

IntroductionNeutrophil-to-lymphocyte ratio (NLR) is a surrogate for systemic inflammatory response and its elevation has been shown to be a poor prognostic factor in various malignancies. Stereotactic radiosurgery (SRS) can induce a leukocyte-predominant inflammatory response. This study investigates the prognostic impact of post-SRS NLR in patients with brain metastases (BM).MethodsBM patients treated with SRS from 2003 to 2015 were retrospectively identified. NLR was calculated from the most recent full blood counts post-SRS. Overall survival (OS) and intracranial outcomes were calculated using the Kaplan–Meier method and cumulative incidence with competing risk for death, respectively.Results188 patients with 328 BM treated with SRS had calculable post-treatment NLR values. Of these, 51 (27.1%) had a NLR > 6. The overall median imaging follow-up was 13.2 (14.0 vs. 8.7 for NLR ≤ 6.0 vs. > 6.0) months. Baseline patient and treatment characteristics were well balanced, except for lower rate of ECOG performance status 0 in the NLR > 6 cohort (33.3 vs. 44.2%, p = 0.026). NLR > 6 was associated with worse 1- and 2-year OS: 59.9 vs. 72.9% and 24.6 vs. 43.8%, (p = 0.028). On multivariable analysis, NLR > 6 (HR: 1.53; 95% CI 1.03–2.26, p = 0.036) and presence of extracranial metastases (HR: 1.90; 95% CI 1.30–2.78; p < 0.001) were significant predictors for worse OS. No association was seen with NLR and intracranial outcomes.ConclusionPost-treatment NLR, a potential marker for post-SRS inflammatory response, is inversely associated with OS in patients with BM. If prospectively validated, NLR is a simple, systemic marker that can be easily used to guide subsequent management.

Outcomes and Practice Patterns for Aggressive Local Therapy in Newly Diagnosed Stage IV Soft Tissue Sarcoma: An NCDB Analysis

Time Session Type Abstract # Author Title Innovation Hub, Exhibit Hall 3 1:15PM 2:45PM Poster Viewing Q&A 1 2204 Benjamin Fischer-Valuck, MD Effectiveness of Adjuvant Radiation Therapy After Radical Cystectomy for Locally Advanced Bladder Cancer Innovation Hub, Exhibit Hall 3 1:15PM 2:45PM Poster Viewing Q&A 1 2035 Neil Pfister, MD, PhD HIV-Positive Anal Cancer Patients Treated with Definitive Chemoradiation: Factors Impacting Clinical Outcomes Innovation Hub, Exhibit Hall 3 1:15PM 2:45PM Poster Viewing Q&A 1 2152 Daniel Tanenbaum, MD Size of hepatic metastases on PET/CT versus pathologic specimen: implications for radiation treatment planning Stars at Night Ballroom 3:45PM 3:55PM Clinical Trials Session 01 3 Deborah Bruner, PhD, RN, FAAN Patient Reported Outcomes of NRG Oncology/RTOG 0232: A Phase III Study Comparing Combined External Beam Radiation and Transperineal Interstitial Permanent Brachytherapy with Brachytherapy Alone in Intermediate Risk Prostate Cancer

Postoperative stereotactic radiosurgery for resected brain metastases: A comparison of outcomes for large resection cavities

PURPOSE Although historical trials have established the role of surgical resection followed by whole brain irradiation (WBRT) for brain metastases, WBRT has recently been shown to cause significant neurocognitive decline. Many practitioners have employed postoperative stereotactic radiosurgery (SRS) to tumor resection cavities to increase local control without causing significant neurocognitive sequelae. However, studies analyzing outcomes of large brain metastases treated with resection and postoperative SRS are lacking. Here we compare outcomes in patients with large brain metastases >4 cm to those with smaller metastases ≤4 cm treated with surgical resection followed by SRS to the resection cavity. METHODS AND MATERIALS Consecutive patients with brain metastases treated at our institution with surgical resection and postoperative SRS were retrospectively reviewed. Patients were stratified into ≤4 cm and >4 cm cohorts based on preoperative maximal tumor dimension. Cumulative incidence of local failure, radiation necrosis, and death were analyzed for the 2 cohorts using a competing-risk model, defined as the time from SRS treatment date to the measured event, death, or last follow-up. RESULTS A total of 117 consecutive cases were identified. Of these patients, 90 (77%) had preoperative tumors ≤4 cm, and 27 (23%) >4 cm in greatest dimension. The only significant baseline difference between the 2 groups was a higher proportion of patients who underwent gross total resection in the ≤4 cm compared with the >4 cm cohort, 76% versus 48%, respectively (P <.01). The 1-year rates of local failure, radiation necrosis, and overall survival for the ≤4 cm and >4 cm cohorts were 12.3% and 16.0%, 26.9% and 28.4%, and 80.6% and 67.6%, respectively (all P >.05). The rates of local failure and radiation necrosis were not statistically different on multivariable analysis based on tumor size. CONCLUSIONS Brain metastases >4 cm in largest dimension managed by resection and radiosurgery to the tumor cavity have promising local control rates without a significant increase in radiation necrosis on our retrospective review.

Pretreatment diffusion weighted imaging for clinical outcome assessment in patients undergoing definitive chemoradiation for pancreatic adenocarcinoma.

432 Background: Factors predicting patterns of failure for pancreatic ductal adenocarcinoma (PDA) are not well-established. Diffusion-weighted MRI (DWI) is useful in predicting recurrence for other gastrointestinal malignancies. The purpose of this study was to evaluate for correlation between tumor DWI parameters and clinical outcomes following chemoradiotherapy (CRT) for pancreatic adenocarcinoma. Methods: From 2009 to 2013, 27 patients with locally advanced (n=14), borderline resectable (n=12) or resectable (n=1) PDA underwent CRT. All patients received upfront FOLFIRINOX or gemcitabine-based chemotherapy prior to CRT, and gemcitabine (median weekly dose 800 mg/m2) concurrent with radiotherapy. DWI was obtained during radiotherapy treatment planning, and apparent diffusion coefficient (ADC) maps were generated to allow determination of median tumor ADC. Tumor-directed CRT was administered with respiratory gated intensity modulated radiation therapy, 55Gy in 25 fractions without elective nodal coverage....