Longer Overall Survival In Patients Research Articles

Treatment Patterns and Associated Outcomes in Patients with Relapsed or Refractory Multiple Myeloma in the US and Non-US Countries: Findings from Preamble

Introduction: The management of multiple myeloma (MM) has undergone profound changes over the recent past due to newer therapeutic agents with novel mechanisms of action and refinement of treatment strategies. Proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and 3-drug regimens involving a PI and an IMiD (PI+IMiD) have become standards of care in MM. The immuno-oncology (I-O) agents elotuzumab and daratumumab were approved to treat relapsed or refractory (RR) MM by the US Food and Drug Administration in 2015, and by the European Medicines Agency in 2016. Extension of survival for patients with MM is a realistic goal, although access to therapies may vary between the US and non-US countries. Comparison of treatment patterns and associated outcomes for patients with RRMM in the US with non-US countries will shed light on the impact of treatment access on patient outcomes.Methods:Patients from the US and 5 non-US countries (Canada, France, Germany, Italy, and UK), ≥18 y of age with RRMM, ≥1 prior systemic therapy, and initiating treatment with a PI, an IMiD, a PI+IMiD combination, or an I-O agent within 90 d before or 30 d after study consent, were identified from PREAMBLE, an ongoing, prospective, non-interventional observational study (NCT01838512). Patient data were collected at each healthcare provider visit over a 3-y period or until the end of patient follow-up. Statistical comparisons were made using t tests and Mann-Whitney U tests for continuous variables and chi-square tests for categorical variables; 2-sided p-values were obtained. Overall survival (OS) was analyzed using Cox regression and Kaplan-Meier techniques.Results: 1075 patients with RRMM (median age 69 y; 57.2% male) were enrolled; 341 (31.7%) from the US and 734 (68.3%) from non-US countries. At data cut-off (May 27, 2017), 522 (48.6%) patients had withdrawn from the study; 357 (68.4%) of patients who had withdrawn had died, mainly due to disease progression. Median follow-up was 18.7 mo (interquartile range: 8.8-31.5 mo). Patients from the US and non-US countries were similar with regard to sex, disease status, and International Staging System stage, although compared with patients from non-US countries, patients from the US were younger at baseline, had more comorbidities, and received more prior lines of treatment (Table).The proportion of patients receiving treatment in a subsequent line was similar between the US and non-US countries (54.3% vs 54.8%). Significantly more patients from the US received 2 or more subsequent therapies than patients from non-US countries (63.6% vs 53.4%; p=0.007). In addition, compared with patients from non-US countries, patients from the US were significantly more likely to receive I-O agents (8.2% vs 1.2%, p<0.001), and all newer agents (37.5% vs 13.4%, p<0.001), including the I-O agents elotuzumab and daratumumab, the PIs carfilzomib and ixazomib, the IMiD pomalidomide, and the histone deacetylase inhibitor panobinostat.Median OS was longer for patients from the US than for patients from non-US countries (32.0 vs 28.6 mo), although the difference was not statistically significant (p=0.831). After adjusting for baseline differences between the US and non-US countries, mortality among patients from non-US countries was 30% higher than among patients from the US (hazard ratio 1.30; 95% CI 0.94-1.80; p=0.108).Conclusion: This pilot analysis of data from a clinical setting shows that patients with RRMM in the US had greater access to newer agents and received more subsequent therapies than patients in non-US countries. The longer OS in patients from the US may suggest clinical benefit associated with newer agents. Future analysis may be necessary to validate our findings.Study support:Bristol-Myers Squibb. [Display omitted] DisclosuresVij:Celgene, Onyx, Takeda, Novartis, BMS, Sanofi, Janssen, Merck: Consultancy; Takeda, Onyx: Research Funding. Chen:Bristol-Myers Squibb: Employment. Popov:Parexel: Employment. Durie:Johnson & Johnson: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Cook:Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Honoraria; Glycomimetcs: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Zyczynski:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment. Goldschmidt:Bristol-Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Onyx: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Chugai: Consultancy, Honoraria, Research Funding, Speakers Bureau; Morphosys: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Research Funding, Speakers Bureau.

Dysregulated circ_0004913, circ_0008160, circ_0000517, and their potential as biomarkers for disease monitoring and prognosis in hepatocellular carcinoma.

Circular RNA_0004913 (circ_0004913), circular RNA_0008160 (circ_0008160), and circular RNA_0000517 (circ_0000517) are shown to be dysregulated in HCC tissues and cell lines, and also show potential in regulating hepatocellular carcinoma (HCC) pathogenesis. This current study attempted to find possible associations of circ_0004913, circ_0008160, and circ_0000517 with clinical features and prognosis of HCC patients. A hundred and fifty HCC patients who received hepatectomy were retrospectively reviewed, and their resected specimens including tumor tissues and paired adjacent tissues were obtained, in which the circ_0004913, circ_0008160, and circ_0000517 expressions were detected. Overall survival (OS) data were collected according to the clinical visit records. Circ_0004913 (p<0.001) and circ_0008160 (p<0.001) were downregulated, while circ_0000517 (p<0.001) was upregulated in tumor tissue compared with paired adjacent tissue. Additionally, tumor circ_0004913 was negatively associated with largest tumor size (p=0.009) and Barcelona clinic liver cancer (BCLC) stage (p=0.020), while tumor circ_0008160 and circ_0000517 were not correlated with any clinicopathological features of HCC patients (all p>0.05). Tumor circ_0004913 high expression was associated with prolonged OS in total HCC patients (p=0.008) and in subgroup of patients with largest tumor size <5cm (p=0.008). Tumor circ_0008160 high expression was correlated with longer OS in patients with BCLC stage B (p=0.026). Univariate Cox's analysis disclosed that tumor circ_0004913 high expression was correlated with longer OS; while after adjustment by multivariate Cox's analysis, it failed to predict OS independently. Circ_0004913 was downregulated in tumor tissue and may serve as a biomarker for evaluating disease severity and prognosis in HCC patients.

TGFβ1 in Cancer-Associated Fibroblasts Is Associated With Progression and Radiosensitivity in Small-Cell Lung Cancer.

ObjectiveSmall-cell lung cancer (SCLC) is aggressive, with early metastasis. Cytokines secreted by cancer-associated fibroblasts (CAFs) within various tumors influences these features, but the function in particular of TGFβ1 (transforming growth factor beta 1) is controversial and unknown in SCLC. This study explored the influence of TGFβ1 in CAFs on the development, immune microenvironment, and radiotherapy sensitivity of SCLC.MethodsSCLC specimens were collected from 90 patients who had received no treatment before surgery. Tumor and tumor stroma were subjected to multiplex immunohistochemistry to quantitate TGFβ1 and other immune factors in CAFs. Cell proliferation and flow cytometry apoptosis assays were used to investigate associations between TGFβ1 and proliferation and radiotherapy sensitivity. The immune factors in tumors were detected by immunohistochemistry in vitro and in vivo (mice).ResultsTGFβ1 levels on CAFs lower or higher than the median were found, respectively, in 52.2 and 47.8% of patients; overall survival of patients with TGFβ1-high levels (53.9 mo) was significantly longer than that of the TGFβ1-low group (26.9 mo; P = 0.037). The univariate and multivariate analyses indicated that a TGFβ1-high level was an independent predictor of increased survival time. TGFβ1-high levels in CAFs were associated with inhibition of growth, proliferation, antitumor immunity, and enhanced radiotherapeutic sensitivity and tumor immunity of tumor. TGFβ1-low levels promoted tumor cell growth and radiotherapy sensitivity in vivo and in vitro.ConclusionHigh levels of TGFβ1 in CAFs were associated with longer overall survival in patients with SCLC and enhanced radiotherapy sensitivity.

Association between Body Mass Index and Survival Outcome in Metastatic Cancer Patients Treated by Immunotherapy: Analysis of a French Retrospective Cohort.

Simple SummaryImmunotherapy has considerably changed the outcomes of cancer patients. However, only a minority of patients respond to immunotherapy and may suffer toxicity. Moreover, strong predictive and prognostic markers are lacking. The number of overweight and obese individuals is steadily increasing in developed countries. This factor is easy to measure and leads to a chronic inflammatory state. We therefore evaluated the relationships between body mass index, survival, and immune-related adverse events in patients treated by immunotherapy for metastatic cancer. Overall survival was better in patients with a BMI ≥ 25 and in those experiencing toxicity. More than 60% of obese patients experienced toxicity. These results should raise the awareness of physicians concerning the importance of body composition in the management of patients on immunotherapy. Body composition, including lean and fat tissue proportions, could be analyzed by CT scans in this selected population.The response to immunotherapy has been little investigated in overweight and obese cancer patients. We evaluated the relationships between BMI, toxicity, and survival in patients treated by immunotherapy for metastatic cancer. We included metastatic cancer patients treated by immunotherapy between January 2017 and June 2020 at the Centre Léon Bérard. In total, 272 patients were included: 64% men and 36% women, with a median age of 61.4 years. BMI ≥ 25 in 34.2% and 50% had non-small cell lung cancer (n = 136). Most received monotherapy, with nivolumab in 41.9% and pembrolizumab in 37.9%. Toxicity, mostly dysthyroiditis, occurred in 41%. Median overall survival (OS), estimated by Kaplan–Meier analysis, was significantly longer for patients with a BMI ≥ 25 than for those with a BMI < 25 (24.8 versus 13.7 months HR = 0.63; 95% CI 0.44–0.92, p = 0.015), and for patients experiencing toxicity than for those without toxicity (NR versus 7.8 months, HR = 0.22; 95% CI 0.15–0.33, p < 0.001). Adjusted OS was associated with toxicity, and the occurrence of toxicity was associated with sex and histological features but not with BMI. Thus, being overweight and experiencing toxicity was associated with longer overall survival in patients treated by immunotherapy. More attention should be paid to body composition in the care of cancer patients.

Impact of Clinical Trial Participation on Survival of Patients with Metastatic Non-Small Cell Lung Cancer

IntroductionThe impact of clinical trial participation on overall survival is unclear. We hypothesized that enrollment in a therapeutic drug clinical trial is associated with longer overall survival in patients with metastatic non-small cell lung cancer (NSCLC). Patients and MethodsWe linked electronic medical record and Washington State cancer registry data to identify patients with metastatic NSCLC diagnosed between January 1, 2007, and December 31, 2015 who received treatment at a National Cancer Institute–designated cancer center. The exposure was trial enrollment. The primary outcome was overall survival, defined as the date of second-line treatment initiation to date of death or last follow-up. We used a conditional landmark analysis starting at the date of second-line treatment initiation and propensity scores with inverse probability of treatment weighting to estimate the association between trial enrollment and survival. ResultsOf 215 patients, 40 (19%) participated in a second-line trial. Trial participants were more likely to be never smokers (45% vs 27%), have a good performance status (88% vs 77%) and have EGFR (48% vs 14%) and ALK mutations (8% vs 5%) than nonparticipants. Trial participants had similar overall survival to nonparticipants (HR 1.05; 95% CI, 0.72, 1.53; p = 0.81) after adjusting for sociodemographic and disease characteristics. ConclusionAccounting for the immortal time bias and selection bias, trial participation does not appear detrimental to survival. This finding may be reassuring to patients and supports programs and policies to improve clinical trial access.

Early Administration of Convalescent Plasma Improves Survival in Patients with Hematological Malignancies and COVID-19.

The use of convalescent plasma in the treatment of COVID-19 may lead to a milder course of infection and has been associated with improved outcomes. Determining optimal treatments in high risk populations is crucial, as is the case in those with hematological malignancies. We analyzed a cohort of 23 patients with hematological malignancies and COVID-19 who had received plasma 48–72 h after the diagnosis of infection and compared it with a historical group of 22 patients who received other therapy. Overall survival in those who received convalescent plasma was significantly higher than in the historical group (p = 0.03460). The plasma–treated group also showed a significantly milder course of infection (p = 0.03807), characterized by less severe symptoms and faster recovery (p = 0.00001). In conclusion, we have demonstrated that convalescent plasma is an effective treatment and its early administration leads to clinical improvement, increased viral clearance and longer overall survival in patients with hematological malignancies and COVID-19. To our knowledge, this is the first report to analyze the efficacy of convalescent plasma in a cohort of patients with hematological malignancies.

Impact of lung metastases on overall survival in the phase 3 SELECT study of lenvatinib in patients with radioiodine-refractory differentiated thyroid cancer

BackgroundLung metastases may worsen overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). We investigated (post hoc) the impact of lung metastases on survival in SELECT (a phase 3 study). Patients and methods392 patients with RR-DTC were randomised 2:1 to lenvatinib 24 mg daily (n = 261) or placebo (n = 131). Placebo-treated patients could crossover to open-label lenvatinib following progression. Patients were grouped by size of baseline lung metastases. Safety/efficacy outcomes, collated by these lung-metastases subgroups, were generated. ResultsLenvatinib-treated population distributions per baseline lung metastases subgroup were any lung metastases (target/nontarget lesions; n = 226), and by maximum size of target lung lesions ≥1.0 cm (n = 199), ≥1.5 cm (n = 150), ≥2.0 cm (n = 94) and <2.0 cm (n = 105). In patients with any lung metastases, no statistically significant difference in OS was observed between treatment arms (HR: 0.76; 95% CI: 0.57–1.01; P = 0.0549). Median OS for lung metastases of ≥1.0 cm was 44.7 months (lenvatinib) versus 33.1 months (placebo) (HR: 0.63; 95% CI: 0.47–0.85; P = 0.0025). OS was significantly prolonged with lenvatinib versus placebo among patients with lung metastases of ≥1.0 cm, ≥1.5 cm, ≥2.0 cm and <2.0 cm; median OS was shorter in the ≥2.0 cm subgroup (lenvatinib: 34.7 months) versus other subgroups (lenvatinib: 44.1–49.2 months). Multivariate analysis demonstrated lenvatinib significantly prolonged OS in patients with lung metastases of ≥1.0 cm after adjustment for baseline characteristics. ConclusionsLenvatinib treatment resulted in longer OS in patients with lung metastases of ≥1.0 cm versus placebo (even with the 89% crossover rate). Early initiation of lenvatinib may improve outcomes in patients with RR-DTC and lung metastases of ≥1.0 cm. Source study registrationClinicalTrials.Gov Identifier: NCT01321554.

The Expression of NRIP1 and LCOR in Endometrioid Endometrial Cancer.

The aim of the study was to analyze the expression of nuclear receptor interacting protein 1 (NRIP1) and its partner ligand-dependent nuclear receptor co-repressor (LCOR) in endometrioid endometrial cancer and to investigate their association with estrogen receptor (ER), progesterone receptor (PR), Ki-67, clinicopathological parameters and patient survival. Immunohistochemical evaluation was carried out to investigate the subcellular expression of NRIP1 and LCOR in endometrioid endometrial cancer samples. Statistical analysis was used to identify the correlations of NRIP1 and LCOR expression with clinicopathological variables and to estimate the survival rates. Endometrial cancer tissues exhibited higher expression of NRIP1 and LCOR in comparison with the normal tissues. Cytoplasmic LCOR expression was positively associated with ER and PR expression, while cytoplasmic NRIP1 expression was positively associated with ER expression. Moreover, cytoplasmic expression of NRIP1 was positively associated with Ki-67. Our study demonstrated that high cytoplasmic expression of LCOR may predict a longer overall survival of patients with endometrioid endometrial cancer. Patients with tumors expressing low levels of LCOR showed a worse survival compared to those expressing high levels.

Targeting Tumor-Induced Immunosuppression Using Conventional Cancer Therapeutics

Immunosuppression remains a challenge in the immunotherapy field and needs to be combated to increase survival of patients suffering from cancer. There have been no phase III trials that have in an organized, statistically reliable setting compared immunotherapy outcome with or without so called preconditioning, or metronomic conditioning, in randomized settings. The current view on preconditioning is that it may be used both to reduce tumor load and to reduce suppressive immune cells prior to immunotherapy. For combination treatments, immunotherapy such as checkpoint blockade has shown benefit in combination with chemotherapy even if the major goals of those studies may not have been to condition the patient for a better immune response due to reduced immunosuppression. Nevertheless, there is a need to further enhance the promising effect of cancer immunotherapy. We argue herein that there are several interesting conventional cancer therapeutics to explore for combinational use with immunotherapy to enhance response rates and achieve a longer overall survival of patients. This review will discuss mechanisms of conventional cancer therapeutics of interest for combination therapy. For example, gemcitabine and several tyrosine kinase inhibitors have profound effect on myeloid-derived suppressor cells while tyrosine kinase inhibitors can enhance T cell infiltration into tumors likely due to increased chemokine signaling. Further, cyclophosphamide is well known for its capacity to reduce Tregs and is used to precondition patients prior T cell therapy. How to combine these agents with immunotherapy to further increase patient survival is an important next step in the immunotherapeutic field.

CES2 Expression in Pancreatic Adenocarcinoma Is Predictive of Response to Irinotecan and Is Associated With Type 2 Diabetes.

The combination chemotherapy of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) has provided clinically meaningful improvement for pancreatic ductal adenocarcinoma (PDAC). We previously uncovered a role for the serine hydrolase carboxylesterase 2 (CES2) in mediating intratumoral activation of the prodrug irinotecan, a constituent of FOLFIRINOX. We aimed to further test the predictive value of CES2 for response to irinotecan using patient-derived xenograft (PDX) models and to elucidate the determinants of CES2 expression and response to FOLFIRINOX treatment among patients with PDAC. PDXs were engrafted subcutaneously into nude mice and treated for 4 weeks with either saline control or irinotecan. CES2 and hepatocyte nuclear factor 4 alpha (HNF4A) expression in PDAC tissues was evaluated by immunohistochemical and Western blot analysis. Kaplan-Meier and Cox regression analyses were applied to assess the association between overall survival and hemoglobin A1C (HbA1C) levels in patients who underwent neoadjuvant FOLFIRINOX treatment. High CES2 activity in PDAC PDXs was associated with increased sensitivity to irinotecan. Integrated gene expression, proteomic analyses, and in vitro genetic experiments revealed that nuclear receptor HNF4A, which is upregulated in diabetes, is the upstream transcriptional regulator of CES2 expression. Elevated CES2 protein expression in PDAC tissues was positively associated with a history of type 2 diabetes (odds ratio, 4.84; P = .02). High HbA1C levels were associated with longer overall survival in patients who received neoadjuvant FOLFIRINOX treatment (P = .04). To our knowledge, we provide, for the first time, evidence that CES2 expression is associated with a history of type 2 diabetes in PDAC and that elevated HbA1C, by predicting tumor CES2 expression, may represent a novel marker for stratifying patients most likely to respond to FOLFIRINOX therapy.

Systemic analyses of expression patterns and clinical features for GIMAPs family members in lung adenocarcinoma.

GTPase of immunity-associated proteins (GIMAPs) are frequently prescribed as important components of immune regulation complexes, which were known to play key roles in lung adenocarcinoma. However, little is known about the function of distinct GIMAPs in lung adenocarcinoma. To address this issue, this study investigated the biological function and pathway of GIMAPs in lung adenocarcinoma using multiple public databases. Absent expression of GIMAPs was found in lung adenocarcinoma at mRNA and protein levels. While a purity-corrected value uncovered that all GIMAPs were positively associated with the immune infiltration of lung adenocarcinoma. Furthermore, the expressions of GIMAPs were considered to be negatively associated with clinical cancer stages, patient’s gender and pathological tumor grades in patients with lung adenocarcinoma. Besides, higher mRNA expression of GIMAPs was significantly associated with longer overall survival of patients with lung adenocarcinoma. Taken together, these results may enable GIMAPs family members as diagnostic and survival biomarker candidates or even potential therapeutic targets for patients with lung adenocarcinoma.

Alterations of DNA damage response genes correlate with response and overall survival in anti-PD-1/PD-L1-treated advanced urothelial cancer.

DNA damage response (DDR) gene alterations in cancer are associated with a higher tumor mutational burden (TMB) and may impact clinical outcomes of urothelial cancer (UC). Here, we explore the prognostic role of DDR alterations in advanced UC treated with anti‐PD‐1/PD‐L1 agents. The study included 53 patients who had FoundationOne genomic sequencing and received anti‐PD‐1/PD‐L1 therapy. Fisher exact test and trend test were used to assess differences in objective response rate (ORR). Overall survival (OS) was measured from the time of initial UC diagnosis and Cox proportional hazard regression analysis was performed to calculate hazard ratio (HR) and 95% confidence interval (CI). The cohort had a median age of 66 with 64% receiving platinum‐based chemotherapy. DDR alterations (including ATM) were associated with a non‐significantly higher ORR to PD‐1/PD‐L1 blockade (41% vs. 21%, p = 0.136). Patients with DDR alterations (excluding ATM) had non‐significantly longer OS, likely due to a small sample size (HR = 0.53, 95% CI 0.20–1.38, p = 0.19). ATM alterations were associated with a non‐significantly higher ORR (40% vs. 29%, p = 0.6), but also with significantly shorter OS (HR = 5.7, 95% CI 1.65–19.74, p = 0.006). Patients with ≥ 3 DDR alterations (including ATM) had substantially higher TMB (p = 0.01) and higher ORR (80%) with PD‐1/PD‐L1 blockade versus 24% ORR in patients with <3 DDR alterations. In summary, DDR alterations were associated with non‐significantly higher ORR and longer OS for patients with advanced UC receiving anti‐PD‐1/PD‐L1 agents. ATM alterations were associated with shorter OS.

Comparison of Efficacy and Peripheral Neuropathy of Solvent-based Paclitaxel with Paclitaxel Poliglumex and NK105: A Systematic Review and Metaanalysis.

The article was reported in accordance with PRISMA Guidelines (Registration number: CRD42021245313). We conducted a meta-analysis to compare the incidence and severity of peripheral neuropathy between solvent-based paclitaxel, PPX and NK105 mono-chemotherapy. Results revealed that no significant difference exists between the incidence of all grade peripheral neuropathy among the solvent-based paclitaxel, PPX and NK105 treated groups. While, the incidence of high grade peripheral neuropathy induced by NK105 was lower than two other groups. Moreover, the overall survival was not improved in PPX compared with other groups. However, NK105 demonstrated significant longer overall survival in patients with cancer. Current evidence suggests more attention should be paid to the paclitaxel poliglumex re-formulation.

Effect of Whole-Brain and Intensity-Modulated Radiotherapy on Serum Levels of miR-21 and Prognosis for Lung Cancer Metastatic to the Brain.

BackgroundThe goal of the present study was to explore the influence of whole-brain radiotherapy (WBRT) and intensity-modulated radiotherapy (IMRT) on serum levels of miR-21 and prognosis for lung cancer that has metastasized to the brain.Material/MethodsTwo hundred patients with lung cancer metastatic to the brain were randomized, half to the control group and half to the observation group. The observation group received WBRT and reduced-field IMRT (WBRT+RF-IMRT) and the control group received conventional-field IMRT (CF-IMRT). The total effective rate after treatment was determined. Serum levels of miR-21 were measured before and after radiotherapy with reverse transcriptase-polymerase chain reaction. In addition, tumor marker levels were measured with enzyme-linked immunosorbent assay. The relationship between miR-21 levels and tumor marker levels was assessed with a Pearson correlation coefficient test. Five-year survival was estimated with Kaplan-Meier curves.ResultsThe total effective rate was higher in the observation group (86%) than in the control group (69%). Lower levels of miR-21 and tumor markers were seen in the observation group. Moreover, miR-21 levels were positively correlated with levels of tumor necrosis factor-α, neuron-specific enolase, SCC-Ag, and carcinoembryonic antigen. Low levels of miR-21 were associated with longer overall survival in patients with lung cancer metastatic to the brain.ConclusionsWBRT+RF-IMRT is superior to CF-IMRT for lung cancer metastatic to the brain. MiR-21 may be a marker for prediction of the efficacy of radiotherapy in this disease setting.

The Association Between the Extent of Glioblastoma Resection and Survival in Light of MGMT Promoter Methylation in 326 Patients With Newly Diagnosed IDH-Wildtype Glioblastoma.

Background: The association between contrast enhanced (CE) and non-contrast enhanced (NCE) tumor resection and survival in patients with glioblastoma in relation to molecular subtypes is poorly understood. The aim of this study was to assess the association between CE and NCE tumor resection and survival in light of MGMT promoter methylation in newly diagnosed IDH-wildtype glioblastoma.Materials and methods: Patients with newly diagnosed IDH-wildtype glioblastoma who underwent surgery were eligible. CE and NCE tumor volumes were assessed on pre- and post-operative MRI scans and extent of resection was calculated. The association between CE and NCE tumor resection and survival was evaluated using multivariable Cox proportional hazards models and Kaplan Meier estimates.Results: Three hundred and twenty-six patients were included: 177 (54.3%) with and 149 (45.7%) without MGMT methylation. Multivariable Cox proportional hazards models stratified for MGMT methylation identified age ≤ 65y (HR 0.63; 95% CI, 0.49–0.81; p < 0.0001), chemoradiation (HR 0.13; 95% CI, 0.09–0.19; p < 0.0001), maximal CE tumor resection (HR 0.58; 95% CI, 0.39–0.87; p = 0.009), ≥ 30% NCE tumor resection (HR 0.71; 95% CI, 0.53–0.93; p = 0.014), and minimal residual CE tumor volume (HR 0.64; 95% CI, 0.46–0.88 p = 0.007) as being associated with longer overall survival. Kaplan Meier estimates showed that extensive surgery was more beneficial for patients with MGMT methylated glioblastoma.Conclusions: This study shows an association between maximal CE tumor resection, ≥30% NCE tumor resection, minimal residual CE tumor volume, and longer overall survival in patients with newly diagnosed IDH wildtype glioblastoma. Intraoperative imaging and stimulation mapping may be used to pursue safe and maximal resection. In future research, the safety aspect of maximizing tumor resection needs to be addressed.

Ablation Therapy for Advanced Stage Non-Small Cell Lung Cancer: A National Cancer Database Study

PurposeTo compare overall survival (OS) of ablation with no treatment for patients with advanced stage non-small cell lung cancer. MethodsPatients with clinical stage IIIB (T1–4N3M0, T4N2M0) and stage IV (T1–4N0–3M1) non-small cell lung cancer, in accordance with the American Joint Committee on Cancer, 7th edition, who did not receive treatment or who received ablation as their sole primary treatment besides chemotherapy from 2004 to 2014, were identified from the National Cancer Data Base. OS was estimated using the Kaplan-Meier method and evaluated by log-rank test, univariate and multivariate Cox proportional hazard regression, and propensity score-matched analysis. Relative survival analyses comparing age- and sex-matched United States populations were performed. ResultsA total of 140,819 patients were included. The 1-, 2-, 3- and 5-year survival rates relative to age- and sex-matched United States population were 28%, 18%, 12%, and 10%, respectively, for ablation (n = 249); and 30%, 15%, 9%, and 5%, respectively for no treatment (n = 140,570). Propensity score matching resulted in 249 patients in the ablation group versus 498 patients in the no-treatment group. After matching, ablation was associated with longer OS than that in the no-treatment group (median, 5.9 vs 4.7 months, respectively; hazard ratio, 0.844; 95% confidence interval, 0.719–0.990; P = .037). These results persisted in patients with an initial tumor size of ≤3 cm. ConclusionsPreliminary results suggest ablation may be associated with longer OS in patients with late-stage non-small cell lung cancer than survival in those who received no treatment.

The effect of primary granulocyte-colony stimulating factor prophylaxis on incidence of febrile neutropenia in patients with testicular germ cell tumors.

e17056 Background: Testicular germ cell tumors (GCTs) represent only one percent of all solid tumors; however, they are the most common solid malignancy in men 15-35 years old. Febrile neutropenia (FN) is a grievous complication of chemotherapy, frequently occurring in GCT patients. The aim of this retrospective study was to assess the effect of primary granulocyte-colony stimulating factor (G-CSF) prophylaxis on the incidence of FN in GCT patients. Methods: This study was conducted using the National Cancer Institute medical records database. Patients diagnosed with germ cell tumors treated with first line/adjuvant chemotherapy at the National Cancer Institute, Bratislava, Slovakia from January 2000 to December 2017 were eligible. Starting in January 2006, patients received G-CSF prophylaxis after every cycle of chemotherapy. Results: Out of 393 patients, 265 patients received primary G-CSF prophylaxis and 128 patients did not receive prophylaxis. The majority of patients (69.97%) were treated with bleomycin, etoposide and cisplatin chemotherapy. There were 61 deaths (15.5%) in our study population. 2- and 5-year OS of the study group was 86.8% and 83.1%, respectively. During the study period, 71 patients (18.1%) suffered FN events. Out of 128 patients who did not receive primary prophylaxis, 42 (32.8%) patients suffered FN, while only 29 (10.9%) patients with primary prophylaxis suffered FN ( P = 0.0000001). On subgroup analysis, FN incidence decreased in all groups with primary prophylaxis, except for patients with stage I GCT receiving adjuvant chemotherapy. Patients receiving G-CSF prophylaxis had significantly longer overall survival when compared to patients without prophylaxis. (HR = 0.44, 95% CI 0.26-0.75; P = 0.0009). Conclusions: Primary G-CSF prophylaxis was associated with significantly decreased FN incidence and longer overall survival in patients treated with first line chemotherapy and should be consider in all patients except stage I disease.

Performance of neoadjuvant therapy in locally advanced adenocarcinoma of the pancreas: A single large volume center experience.

e16745 Background: Pancreatic adenocarcinoma (PC) is a disease with low 5-year survival rates even in patients who undergo surgical resection: ~10% overall and 20-35% in those with negative lymph nodes and R0 operation. Adjuvant chemotherapy (CT) has demonstrated benefit; however, not all patient are candidates for multi-agent CT post-op. Early use of systemic therapy might improve outcomes. As a leading referral center for pancreatic resection in a tri-state area, we present a single institution real-world experience of neoadjuvant CT (neo-CT) in PC patients principally with degrees of vascular abutment at presentation. Methods: We identified 90 patients scheduled for pancreatectomy from 2015 to 2019 who received neo-CT. Three had an aborted procedure due to occult metastatic disease. Of those who underwent resection (n = 87), most were borderline or locally advanced (n = 79) with a few deemed resectable (n = 5) or metastatic (n = 3) prior to CT. 80 patients (92%) had R0 resection, though final pathology showed R1 resection in 5 and distant metastases in 2 patients. 72% of patients (n = 63) received 5-FU-based neo-CT, while 28% (n = 24) received gemcitabine-based CT. 36% (n = 31) received neoadjuvant radiation (RT) (with or without concurrent CT) in addition to CT, and 43% (n = 37) had adjuvant therapy, either CT, RT, or a combination. 4 patients received additional therapies on clinical trial. 41 patients (47%) completed &gt;6 months of peri-operative CT, with 23 of those (26%) completing 6 months prior to surgery. We evaluated pathologic regression scores and compared those with very good response (score 0-1) post-CT vs. partial (score 2) or no response (score 3). Results: Median progression-free survival (PFS) from start of treatment in our cohort was 1.9 years (95% CI 1.4-NR) while median overall survival (OS) was 3.0 years (95% CI 2.4-NR). Duration of neo-CT did not affect PFS or OS. Logrank tests of OS curves of the 3 pathologic response groups indicated a statistically-significant difference (p = 0.004), with longer OS in patients with score 0-1 and shorter OS in patients with score 3. Conclusions: This analysis involves patients treated in both community and academic settings. We observed improved survival among those with best pathologic responses. The majority of cases with lower residual tumor burden received FOLFIRINOX. We are analyzing molecular data in this cohort and will conduct adjusted analyses for clinical characteristics. The prospective selection of multiagent CT in PC may be influenced by molecular profile and early response assessment.

Awake glioma surgery: technical evolution and nuances.

Multiple studies have demonstrated that improved extent of resection is associated with longer overall survival for patients with both high and low grade glioma. Awake craniotomy was developed as a technique for maximizing resection whilst preserving neurological function. We performed a comprehensive review of the literature describing the history, indications, techniques and outcomes of awake craniotomy for patientswith glioma. The technique of awake craniotomy evolved to become an essential tool for resection of glioma. Many perceived contraindications can now be managed. We describe in detail our preferred technique, the testing paradigms utilized, and critically review the literature regarding functional and oncological outcome. Awake craniotomy with mapping has become the gold standard for safely maximizing extent of resection for tumor in or near eloquent brain. Cortical and subcortical mapping methods have been refined and the technique is associated with an extremely low rate of complications.

Prognostic and Clinicopathological Value of PD-L1 in Melanoma: A Meta-Analysis

BackgroundThere is a growing interest in using programmed death ligand-1 (PD-L1) as a prognostic marker for melanoma. We conducted this meta-analysis to explore the prognostic and clinicopathological value of PD-L1 in melanoma. Materials and MethodsThe electronic databases PubMed, Web of Science and the Cochrane Library were searched for relevant studies. The major investigated parameters were PD-L1 expression levels in relation to patient gender, tumor-infiltrating lymphocytes (TILs), tumor stage, lymph node (LN) metastasis, histological type, progression-free survival (PFS) and overall survival (OS). Odds ratios (ORs) and hazard ratios (HRs) were computed using the fixed-effect or random-effects model according to data heterogeneity. ResultsPositive PD-L1 expression was significantly associated with high levels of TILs (OR = 7.56, 95% CI 2.04-28.02), metastatic melanoma (OR = 0.45, 95% CI 0.30-0.67) and LN-positive melanoma (OR = 2.56, 95% CI 1.31-4.99) but not gender or histological type. In addition, the pooled HRs showed no relation between PD-L1 expression and PFS (HR = 1.18, 95% CI 0.83-1.69) or OS (HR = 0.77, 95% CI 0.47-1.25). When restricted to metastatic melanoma, positive PD-L1 expression was significantly related to prolonged OS (HR = 0.57, 95% CI 0.46-0.70). ConclusionsPositive PD-L1 expression may be an important prognostic factor for longer OS in patients with metastatic melanoma.