Radical Prostatectomy versus Intensity Modulated Radiation Therapy in the Management of Localized Prostate Cancer

Purpose: To determine whether radical prostatectomy (RP) or intensity modulated radiation therapy (IMRT) to ≥72 Gy, plus hormonal therapy if indicated, results in improved biochemical disease free survival (BDFS) in localized prostate adenocarcinoma. Methods and Materials: Between 1997-2005, a consecutive sample of 556 patients who underwent RP (n=204) or IMRT (n=352) at two referral centers was analyzed. Patients were stratified into prognostic groups based on clinical stage, Gleason score, and pretreatment prostate specific antigen (PSA) level as outlined by schemes designed by Memorial Sloan Kettering (MSK) and the National Comprehensive Cancer Network (NCCN). The outcome used in this study was BDFS. Median follow up in the RP and IMRT cohorts was 46 months and 40 months, respectively. Results: IMRT patients had more advanced and aggressive disease at baseline (p\u3c.001). No difference was found in five-year BDFS rates between RP and IMRT in the favorable prognosis (92.8% vs. 85.3%, p=.20) or the MSK intermediate prognosis (86.7% vs. 82.2%, p=.46) subsets. A difference favoring IMRT was seen in the NCCN intermediate prognosis (70.7% vs. 83.3%, p=.03), MSK poor prognosis (38.4% vs. 62.2%, p\u3c.001), and NCCN poor prognosis (37.0% vs. 56.8%, p=.005) subsets. Within the entire cohort, after adjustment for confounding variables, Gleason score (p\u3c.001) and clinical stage (p\u3c.001) predicted BDFS, but treatment modality (p=.06) did not. Within the MSK poor prognosis subset, treatment modality (p=.006) was predictive of BDFS, favoring IMRT. Conclusion: Biochemical disease free survival is similar between RP and IMRT for patients with a good prognosis. Patients with a poor prognosis, and some with an intermediate prognosis, may benefit from IMRT to ≥72 Gy plus hormonal therapy

External Validation of Three Prognostic Scores for Brain Metastasis Velocity in Patients Treated with Intracranial Stereotactic Radiotherapy

BACKGROUND AND INTRODUCTION Brain metastasis velocity (BMV) has been proposed as a prognostic factor for overall survival (OS) in patients with brain metastases (BMs). In this study, we conducted an external validation and comparative assessment of the performance of all three BMV scores. MATERIALS AND METHODS Patients treated with intracranial stereotactic radiotherapy (SRT) for BM at a single center between 2014 and 2018 were identified. Where possible, all three BMV scores were calculated. Log-rank tests and linear, logistic and Cox regression analysis were used for validation and predictor identification of OS. RESULTS For 333 of 384 brain metastasis patients, at least one BMV score could be calculated. In a sub-group of 187 patients, "classic" BMV was validated as categorical (p<0.0001) and continuous variable (HR 1.02; 95% CI 1.02-1.03; p<0.0001). In a sub-group of 284 patients, "initial" BMV was validated as categorical variable (high-risk vs. low-risk; p<0.01), but not as continuous variable (HR 1.02; 95% CI 0.99-1.04; p=0.224). "Volume-based" BMV could not be validated in a sub-group of 104 patients. On multivariable Cox regression analysis, iBMV (HR 1.85; 95% CI 1.01-3.38; p<0.05) and cBMV (HR 2.32; 95% CI 1.15 4.68; p<0.05) were predictors for OS for intermediate-risk patients after first SRT and first DBFs, respectively. cBMV proved to be the dominant predictor for OS for high-risk patients (HR 2.99; 95% CI 1.30-6.91; p<0.05). CONCLUSION This study externally validated cBMV and iBMV as prognostic scores for OS in patients treated with SRT for BMs whereas validation of vBMV was not achieved

Estimating survival in patients with gastrointestinal cancers and brain metastases: An update of the graded prognostic assessment for gastrointestinal cancers (GI-GPA).

BackgroundPatients with gastrointestinal cancers and brain metastases (BM) represent a unique and heterogeneous population. Our group previously published the Diagnosis-Specific Graded Prognostic Assessment (DS-GPA) for patients with GI cancers (GI-GPA) (1985-2007, n = 209). The purpose of this study is to update the GI-GPA based on a larger contemporary database.MethodsAn IRB-approved consortium database analysis was performed using a multi-institutional (18), multi-national (3) cohort of 792 patients with gastrointestinal (GI) cancers, with newly-diagnosed BM diagnosed between 1/1/2006 and 12/31/2017. Survival was measured from date of first treatment for BM. Multiple Cox regression was used to select and weight prognostic factors in proportion to their hazard ratios. These factors were incorporated into the updated GI-GPA.ResultsMedian survival (MS) varied widely by primary site and other prognostic factors. Four significant factors (KPS, age, extracranial metastases and number of BM) were used to formulate the updated GI-GPA. Overall MS for this cohort remains poor; 8 months. MS by GPA was 3, 7, 11 and 17 months for GPA 0-1, 1.5-2, 2.5-3.0 and 3.5-4.0, respectively. &gt;30% present in the worst prognostic group (GI-GPA of ≤1.0).ConclusionsBrain metastases are not uncommon in GI cancer patients and MS varies widely among them. This updated GI-GPA index improves our ability to estimate survival for these patients and will be useful for therapy selection, end-of-life decision-making and stratification for future clinical trials. A user-friendly, free, on-line app to calculate the GPA score and estimate survival for an individual patient is available at brainmetgpa.com

Estrogen/progesterone Receptor and HER2 Discordance Between Primary Tumor and Brain Metastases in Breast Cancer and Its Effect on Treatment and Survival

BACKGROUND: Breast cancer treatment is based on estrogen receptors (ERs), progesterone receptors (PRs), and human epidermal growth factor receptor 2 (HER2). At the time of metastasis, receptor status can be discordant from that at initial diagnosis. The purpose of this study was to determine the incidence of discordance and its effect on survival and subsequent treatment in patients with breast cancer brain metastases (BCBM). METHODS: A retrospective database of 316 patients who underwent craniotomy for BCBM between 2006 and 2017 was created. Discordance was considered present if the ER, PR, or HER2 status differed between the primary tumor and the BCBM. RESULTS: The overall receptor discordance rate was 132/316 (42%), and the subtype discordance rate was 100/316 (32%). Hormone receptors (HR, either ER or PR) were gained in 40/160 (25%) patients with HR-negative primary tumors. HER2 was gained in 22/173 (13%) patients with HER2-negative primary tumors. Subsequent treatment was not adjusted for most patients who gained receptors-nonetheless, median survival (MS) improved but did not reach statistical significance (HR, 17-28 mo, P = 0.12; HER2, 15-19 mo, P = 0.39). MS for patients who lost receptors was worse (HR, 27-18 mo, P = 0.02; HER2, 30-18 mo, P = 0.08). CONCLUSIONS: Receptor discordance between primary tumor and BCBM is common, adversely affects survival if receptors are lost, and represents a missed opportunity for use of effective treatments if receptors are gained. Receptor analysis of BCBM is indicated when clinically appropriate. Treatment should be adjusted accordingly. KEY POINTS: 1. Receptor discordance alters subtype in 32% of BCBM patients.2. The frequency of receptor gain for HR and HER2 was 25% and 13%, respectively.3. If receptors are lost, survival suffers. If receptors are gained, consider targeted treatment

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Brain metastases: A Society for Neuro-Oncology (SNO) consensus review on current management and future directions

Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management. Here, in this consensus review supported by the Society for Neuro-Oncology (SNO), we review the landscape of brain metastases with particular attention to management approaches and ongoing efforts with potential to shape future paradigms of care. Each coauthor carried an area of expertise within the field of brain metastases and initially composed, edited, or reviewed their specific subsection of interest. After each subsection was accordingly written, multiple drafts of the manuscript were circulated to the entire list of authors for group discussion and feedback. The hope is that the these consensus guidelines will accelerate progress in the understanding and management of patients with brain metastases, and highlight key areas in need of further exploration that will lead to dedicated trials and other research investigations designed to advance the field

The association of very low PSA with increased cancer-specific death in men with high-grade prostate cancer

62 Background: It has been hypothesized that very low PSAs in men with high-grade prostate cancer could reflect dedifferentiation and a poorer prognosis, but clinical evidence to support this is limited. We sought to determine whether a very low-presenting PSA was associated with greater prostate cancer-specific mortality (PCSM) among men with Gleason score (GS) 8-10 disease. Methods: The Surveillance, Epidemiology and End Results Program was used to identify a national cohort of 328,904 men diagnosed with cT1-4N0M0 prostate cancer between 2004 and 2010. Multivariable Fine-Gray competing-risks regression analysis was used to determine PCSM as a function of PSA level (40ng/mL) and GS (8-10 vs. 40 was 3.19 (2.83-3.59; P<0.001), suggesting a U-shaped distribution. There was a significant interaction between PSA level and GS (Pinteraction<0.001) such that PSA <2.5 only significantly predicted for poorer PCSM among patients with high grade GS 8-10 disease. Conclusions: Among patients with high grade GS 8-10 disease, patients with PSA <2.5 and 2.6-4 appear to have a higher risk for cancer-specific death compared to patients with a 10.1-20 PSA level, supporting the notion that low PSA in GS 8-10 disease may be a sign of underlying aggressive and extremely poorly differentiated or anaplastic low PSA-producing tumors. Patients with low PSA GS 8-10 disease should be considered for clinical trials studying the use of chemotherapy and other novel agents in very-high risk prostate cancers

Trends in Smoking and e-Cigarette Use Among US Patients With Cancer, 2014-2017

This cross-sectional study of data from the National Health Interview Survey analyzes the prevalence of e-cigarette use in US patients with cancer

Health Insurance Affects Head and Neck Cancer Treatment Patterns and Outcomes

The purpose of this study is to examine the effect of insurance coverage on stage of presentation, treatment, and survival of head and neck cancer (HNC). A retrospective study was conducted using the Surveillance, Epidemiology, and End Results (SEER) program to identify patients diagnosed with HNC. The primary variable of interest was insurance analyzed as a dichotomous variable: Patients were considered uninsured if they were classified as "uninsured" by SEER, whereas patients were considered insured if they were defined by SEER as "any Medicaid," "insured," or "insured/no specifics." The outcomes of interest were cancer stage at presentation (M0 vs M1), receipt of definitive treatment, and HNC-specific mortality (HNCSM). Multivariable logistic regression modeled the association between insurance status and stage at presentation, as well as between insurance status and receipt of definitive treatment, whereas HNCSM was modeled using Fine and Gray competing risks. Sensitivity logistic regression analysis was used to determine whether observed interactions remained significant by insurance type (privately insured, Medicaid, and uninsured). Patients without medical insurance were more likely to present with metastatic cancer (adjusted odds ratio, 1.60; P < .001), were more likely to not receive definitive treatment (adjusted odds ratio, 1.64; P < .001), and had a higher risk of HNCSM (adjusted hazard ratio, 1.20; P = .002). Sensitivity analyses showed that when results were stratified by insurance type, significant interactions remained for uninsured patients and patients with Medicaid. Uninsured patients and patients with Medicaid are more likely to present with metastatic disease, are more likely to not be treated definitively, and are at a higher risk of HNCSM. The treatment gap between Medicaid and private insurance observed in this study should serve as an immediate policy target for health care reform