Progression-free Survival Values Research Articles

Shear-wave velocity for colorectal cancer liver metastases as a potential prognostic factor after chemotherapy: a preliminary study

To evaluate whether shear-wave velocity (SWV) can be used for predicting the prognoses of patients with colorectal cancer liver metastases (CRLMs) after chemotherapy. Our institutional review board approved this prospective study, and written informed consent was obtained. SWV of CRLMs were obtained using point shear-wave elastography using acoustic radiation force impulse from 25 patients prior to and 2, 7, and 14 days after chemotherapy. Progression-free survival (PFS) after chemotherapy was estimated using the Kaplan-Meier method. The Cox proportional hazard regression model was used to determine significant predictive factors for PFS. For measurement reproducibility, an additional 37 patients with CRLMs were enrolled and assessed using intraclass correlation coefficients (ICCs). After chemotherapy, 10 and 15 patients were classified into responder and non-responder groups, respectively. The estimated 1- and 3-year PFS values in the whole cohort were 36% and 8%, respectively. A decrease in the SWV value on day 2 relative to the initial value was a significant predictive factor for better PFS outcome (hazard ratio=0.20, 95% confidence interval=0.07-0.57, p=0.003). The estimated 1 and 3-year PFS rates were 66.7% and 22.2%, respectively, in nine patients with decreased SWV values on day 2 and significantly higher than 18.8% and 0% of 16 patients with increased SWV values on day 2. The ICC value of SWV of CRLMs in the additional 37 patients was 0.823 (95% CI=0.685-0.905), indicating good agreement. SWV values of CRLMs could provide prognostic information in patients with CRLMs treated with chemotherapy, as decreased SWV values on day 2 after chemotherapy was a significant predictive factor for better PFS.

Risk Profiling of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients By Measuring Circulating Tumor DNA

Risk Profiling of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients By Measuring Circulating Tumor DNA

Cost-Effectiveness of a 12-Month Fixed Duration of Venetoclax in Combination with Obinutuzumab Versus Chemoimmunotherapy and Other Novel Combinations in First-Line Chronic Lymphocytic Leukemia in Canada

OBJECTIVES: To estimate the cost-effectiveness of venetoclax + obinutuzumab (GAZYVA®, G), (VEN+G) in the treatment of first-line (1L) chronic lymphocytic leukemia (CLL) from a Canadian health care system cost perspective. METHODS: A three-state partitioned-survival model was used to extrapolate progression-free survival (PFS) and overall survival (OS) over a 10-year time horizon. Cost-effectiveness was estimated comparing 12-month fixed duration of VEN+G versus (vs) G + Chlorambucil (GClb) based on the CLL14 clinical trial (NCT02242942). Other comparators included Bendamustine + rituximab (BR), Chlorambucil + rituximab (Clb+R), Ibrutinib (Ibr), Acalabrutinib (Acala) and Acalabrutinib + GAZYVA (Acala+G). VEN+G was also compared to the combination of fludarabine, cyclophosphamide and rituximab (FCR) in the overall 1L CLL population which included unfit and fit patients. Relative efficacy of VEN+G vs other comparators was estimated using a network meta-analysis. Health state utilities and adverse event disutilities were derived from a systematic literature review and other published sources. Costs included CLL treatment, routine care and monitoring, adverse events, disease progression costs, subsequent treatment costs, and end of life care. Uncertainty was assessed using an underlying probabilistic model (probabilistic analysis of uncertainty generated from 5,000 iterations), through deterministic sensitivity analyses (i.e., one-way sensitivity analyses (OWSA)), and through a series of alternative scenario analyses. RESULTS: For the overall unfit 1L CLL patient population, the probabilistic total discounted costs incurred over a 10-year time horizon were as follows: $217,727 for VEN+G vs $312,287 for GClb, $399,219 for BR, $380,713 for Clb+R, $736,017 for Ibr, $868,797 for Acala and $916,139 for Acala+G. The probabilistic total discounted quality adjusted life years (QALYs) were 4.964 for VEN+G vs 4.750, 4.550, 4.422, 4.709, 5.269, and 5.359, respectively for the comparators. For the overall 1L CLL patient population, the probabilistic total discounted costs were $219,651 for VEN+G vs $312,570 for GClb, $342,195 for FCR, $397,262 for BR, $380,551 for Clb+R, $757,129 for Ibr, $868,388 for Acala, and $916,798 for Acala+G. The probabilistic total discounted QALYs were 5.888 for VEN+G vs 5.519, 5.067, 5.198, 5.073, 5.597, 6.259 and 6.380, respectively for the comparators. VEN+G was found to be less costly and more efficacious (i.e., dominant) compared to GClb, BR, Clb+R, Ibr and FCR. As a result, incremental cost utility ratios (ICERs) were not calculated for these comparators. Acala and Acala+G resulted in ICERs ranging from $1.4-$2.1 million per QALY gained relative to VEN+G, which is not cost-effective. Based on the probabilistic model and 5,000 simulations, VEN+G was found to be at least 97% cost-effective across all decision maker willingness-to-pay thresholds. The results from the deterministic model were found to be similar to the probabilistic model. Using the deterministic model, and in comparison to the most commonly prescribed treatment for 1L CLL in Canada (i.e., Ibr), the OWSA comparing VEN+G to Ibr found that the most influential variables in the model were the PFS and OS hazard ratios for Ibr and the utility values for PFS and post-progression survival. CONCLUSION: VEN+G is an effective novel fixed duration treatment option which leads to deep and durable responses for the treatment of patients with unfit 1L CLL and provides excellent value-for-money compared with existing chemoimmunotherapy and treat to progression novel combinations. Disclosures Chatterjee: Pharmerit: Current Employment. Van de Wetering:Pharmerit: Current Employment. Goeree:AbbVie Inc.: Consultancy. Desbois:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzi:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company. Manzoor:AbbVie: Current equity holder in publicly-traded company. Owen:AbbVie, F. Hoffmann-La Roche, Janssen, Astrazeneca, Merck, Servier, Novartis, Teva: Honoraria. Sail:AbbVie Inc.: Current Employment, Current equity holder in publicly-traded company.

Recil 2017 Criteria Demonstrated Similar Prognostic Value and Detected a Comparable Treatment Difference between Obinutuzumab- and Rituximab-Chemotherapy Compared with Cheson 2007 and Lugano 2014 Criteria in Patients with Previously Untreated Advanced-Stage Follicular Lymphoma

Recil 2017 Criteria Demonstrated Similar Prognostic Value and Detected a Comparable Treatment Difference between Obinutuzumab- and Rituximab-Chemotherapy Compared with Cheson 2007 and Lugano 2014 Criteria in Patients with Previously Untreated Advanced-Stage Follicular Lymphoma

Survival Analysis and Prognostic Factors in Prostate Cancer Patients: A Single Center Experience in Eastern Anatolia

Objective: Prostate cancer (PC), one of the most common malignancies of the urogenital tract, is more common in older men and shows significant prognostic differences among individuals. In recent years, new grade groups and American Joint Committee on Cancer (AJCC) stage groups have been used to predict prognosis. However, there is limited information on the prognostic significance of this new system in PC patients in Turkey. In this study, we aimed to evaluate the follow-up results of patients with diagnosis of PC, and the clinical significance of the new prognostic staging system in this patient population in Eastern Anatolia Region.
 Methods: Retrospectively, 141 PC patients being followed up in Erzurum Ataturk University of Medical Oncology Department were included in this study. The relationships between overall survival (OS) and progression free survival (PFS) and clinical-pathological parameters were analysed using Kaplan-Meier curves and compared with the log-rank test. Univariate and multivariate analysis were used to determine the prognostic significance of clinical and pathologic variables for PFS and OS.
 Results: The median age of patients was 69 and the majority of them were stage IV patients (79.4%). The median value of prostate specific antigen (PSA) was 39 ng/mL and the median Gleason score was 8. The majority of the patients had PSA value of ≥ 20 ng / ml (61.7%) and Gleason grade group 5 (35.5%). The median PFS and OS values were 29 and 33 months, respectively. The 5-year survival rates were 50% for local-locoregional disease and 20% for metastatic disease. PFS and OS were longer in patients with good Eastern Cooperative Oncology Group (ECOG) performance status (0-1), early stage (I-II), undergone to surgery, having low PSA (< 10 ng / ml) and low Gleason group (1-2). According to the multivariate analysis; stage, PSA and Gleason grade group were independent prognostic factors for both PFS and OS.
 Conclusion: The new grading system, PSA and AJCC staging system are independent prognostic factors in patients with PC. Considering that patients in our region have shorter life spans compared to the world, these prognostic factors should be used more effectively in daily practice in determination of treatment strategy.

The Predictive Value of Lactate Dehydrogenase in Patients with Chemoradiotherapy for Esophageal Squamous Cell Carcinoma

Increasing evidence has indicated that higher levels of lactate dehydrogenase (LDH) is associated with poor prognosis in various malignancies; however, the correlation between LDH levels and clinical outcomes in esophageal squamous cell carcinoma (ESCC) has been poorly studied. The objective of this study was to assess whether LDH has prognostic value in patients with ESCC undergoing chemoradiotherapy. A total of 614 ESCC patients were enrolled in this retrospective study from January 1, 2012 to December 31, 2016.The optimal cutoff points for LDH were determined by X-tile software. we analyzed the association between the levels of LDH and clinicopathological characteristics, as well as the relationship between LDH levels and responses. Kaplan-Meier method with log-rank test was used to explore the prognostic value for overall survival (OS) and progression-free survival (PFS). And then We examined the prognostic value for OS and PFS by univariate and multivariate Cox regression models. A 1:3 propensity score matching was used to compensate for differences in baseline characteristics. The optimal cutoff points of LDH was 134U/L. The median OS in the high LDH group was 31.3 months, and more than 50% of patients with low LDH were still survive to the last follow-up (P = 0.020).The median PFS of low LDH and high LDH were 40.1 and 18.0 months, respectively (P = 0.010).Gender,Cyfra21-1,tumor length, cN/M stage, treatment options and LDH were independent prognostic indicators for OS. Gender, Cyfra21-1, tumor length, cN/M stage, treatment options, chemotherapy cycles, and LDH were independent prognostic indicators for PFS. Unfortunately, there was no significant difference for OS and PFS by Kaplan–Meier method after matching, but the survival curve showed a tendency to separate between the two groups. The present study revealed the existence of a significant association between the pretreatment serum LDH level and OS in patients with ESCC receiving treatment with chemoradiotherapy as well as a significant association with PFS. It implied that the management of patients with high LDH levels should be changed. However, it is worth noting that this conclusion was not certified after matching. Although the consistent conclusions were not obtained in predicting the prognosis of ESCC patients with LDH before and after matching, a multicenter, large-sample prospective study is needed to further verify the conclusions of this study before this method can be applied to conventional clinical studies.

Prognostic Value of Serum Soluble Programmed Death-Ligand 1 and Dynamics During Chemotherapy in Advanced Gastric Cancer Patients.

PurposeThe soluble form programmed death-ligand 1 (sPDL1) has immunosuppressive properties and is being studied as a candidate biomarker for immuno-oncology drug development. We measured the serum sPDL1 at pre-and post-chemotherapy and evaluated its prognostic implication and dynamics during chemotherapy in advanced gastric cancer (GC).Materials and MethodsWe prospectively enrolled 68 GC patients who were candidates for palliative standard first-line chemotherapy, and serially collected blood at baseline and after one cycle of chemotherapy, at the best response and after disease progression. sPDL1 was measured using an enzyme-linked immunosorbent assay. Response to chemotherapy, overall survival (OS), progression-free survival (PFS) and other prognostic factors including neutrophil-lymphocyte ratio (NLR) were obtained. The cut-off value of sPDL1 levels for survival analysis was found using C-statistics.ResultsThe median baseline sPDL1 was 0.8 ng/mL (range, 0.06 to 6.06 ng/mL). The median OS and PFS were 14.9 months and 8.0 months, respectively. sPDL1 and NLR showed a weak positive correlation (Spearman’s rho=0.301, p=0.013). Patients with low levels of sPDL1 at diagnosis (< 1.92 ng/mL) showed a better OS and PFS than patients with a high sPDL1. The baseline sPDL1 before treatment was higher in the progressive disease group than in the stable disease and partial response groups. Patients whose sPDL1 increased after the first cycle of chemotherapy showed worse PFS and OS. Following disease progression, sPDL1 increased compared with the baseline.ConclusionsPDL1 at prechemotherapy confers a prognostic value for PFS and OS in GC patients under palliative first-line chemotherapy. Dynamics of sPDL1 during chemotherapy correlates with disease progression.

Comparative Efficacy of Acalabrutinib in Frontline Treatment of Chronic Lymphocytic Leukemia: A Systematic Review and Network Meta-analysis

PurposeThe goal of this study was to estimate the relative efficacy of acalabrutinib (monotherapy and in combination with obinutuzumab) compared with standard frontline treatments for chronic lymphocytic leukemia (CLL) in fludarabine-ineligible patients, through a network meta-analysis (NMA). MethodsThe efficacy of acalabrutinib from ELEVATE-TN (study of Obinutuzumab + Chlorambucil, Acalabrutinib [ACP-196] + Obinutuzumab, and Acalabrutinib in Subjects With Previously Untreated CLL) was compared to bendamustine + rituximab, chlorambucil-based therapy, alemtuzumab, ibrutinib mono/combination therapy and venetoclax + obinutuzumab using data from eight randomized controlled trials (RCTs). Relevant RCTs were identified using a systematic literature review. Two evidence networks were constructed: Network A, composed solely of RCTs that met the inclusion criteria; and Network B, composed of 7 RCTs and a published cross-trial comparison of ibrutinib from RESONATE-2 and chlorambucil + obinutuzumab from iLLUMINATE. Bayesian NMAs were conducted on progression-free survival (PFS) and overall survival (OS) endpoints; results were reported by using hazard ratios (HRs) and 95% credible intervals (CrIs). HRs were considered significant if their CrIs did not cross 1. Treatments were ranked by using the surface under the cumulative ranking area (SUCRA) values. Expert opinion from 2 hematologists was sought to validate results. FindingsBoth networks showed a significant improvement in PFS for acalabrutinib + obinutuzumab over all comparators. Both networks also showed a significant improvement in PFS for acalabrutinib monotherapy versus most comparators, with a significant difference to ibrutinib monotherapy found in Network A but not Network B. Conversely, a significant difference in PFS was observed for acalabrutinib monotherapy versus venetoclax + obinutuzumab in Network B but not Network A. Although OS HRs all favored acalabrutinib, most were not significant and were characterized by wide CrIs, indicating a high level of uncertainty. Acalabrutinib + obinutuzumab ranked highest in terms of PFS improvement (SUCRA values, 98% and 100%) and OS improvement (SUCRA values, 92% and 94%), followed by acalabrutinib monotherapy (SUCRA values for PFS, 88% and 90%; OS, 83% and 87%) in Networks A and B, respectively. ImplicationsAcalabrutinib was associated with favorable PFS and OS compared with frontline CLL therapies and ranked highest in treatment efficacy over the other comparators. The NMA was limited by heterogeneity in patient baseline characteristics across trials, variable treatment regimens, and short study follow-up times. Despite these limitations, the NMA provides insights into the relative efficacy of acalabrutinib compared with frontline CLL therapies in the absence of head-to-head clinical trials.

Prevalence and Clinical Impact of Concomitant Mutations in Anaplastic Lymphoma Kinase Rearrangement Advanced Non-small-Cell Lung Cancer (Guangdong Association of Thoracic Oncology Study 1055).

Background: In patients with anaplastic lymphoma kinase (ALK) rearrangement-positive advanced non–small-cell lung cancer (NSCLC), ALK inhibitors are now the standard treatment, but their clinical efficacy varies widely for each patient. In this multicenter retrospective study, we evaluated the clinical efficacy of crizotinib according to the ALK rearrangement variants and concomitant mutations present.Patients and Methods: A total 132 patients with ALK rearrangement advanced NSCLC from 4 centers in Guangdong province, China were evaluated. All patients received crizotinib treatment and their ALK rearrangement status was identified by next-generation sequencing (NGS).Results: The median progression-free survival (PFS) in patients with EML4-ALK rearrangement (n = 121), non-EML4-ALK rearrangement (n = 5), and EML4-ALK arrangement accompanied by non-EML4-ALK rearrangement (n = 6) was 12.8, 7.5, and 7.4 months, respectively, with no significant difference between them (p = 0.1554). Similarly, among patients with various EML4-ALK variants (variant 1, variant 3a/b, and other variants), the median PFS values were again comparable. According to baseline NGS data, the median PFS in patients who had ALK rearrangement only, ALK rearrangement and concomitant tumor-suppressor gene mutations, and ALK rearrangement and concomitant oncogene mutations was 14.2, 10.9, and 4.9 months, respectively; (p = 0.0002). A multivariable analysis indicated that concomitant oncogene mutations and tumor-suppressor gene mutations were both negative factors influencing the efficacy of crizotinib in ALK rearrangement NSCLC.Conclusion: Concomitant oncogene mutations and tumor-suppressor gene mutations had negative effects on the efficacy of crizotinib, while various ALK variants had a similar influence.

Combination of CD47 and signal-regulatory protein-α constituting the "don't eat me signal" is a prognostic factor in diffuse large B-cell lymphoma.

The interaction between CD47 and signal‐regulatory protein‐α (SIRPα) inhibits phagocytosis, thus affecting the clinical outcomes of neoplastic diseases. Although CD47 upregulation is associated with poor prognosis in several malignancies, the effect of SIRPα expression and its coexpression with CD47 remains unclear. This study aimed to investigate the clinicopathologic effect of CD47 and SIRPα expression in diffuse large B‐cell lymphoma (DLBCL). Immunostaining of 120 biopsy samples showed that CD47 is primarily expressed in tumor cells, whereas SIRPα is expressed in nonneoplastic stromal cells, mostly macrophages. CD47high cases showed higher MYC protein expression and lower MYC translocation. The SIRPαhigh cases presented significantly shorter overall survival (OS) and progression‐free survival (PFS) than SIRPαlow cases in the activated B‐cell (ABC) subtype of DLBCL (P = .04 and P = .02, respectively). Both CD47high and SIRPαhigh presented significantly shorter OS and PFS than other cases among all DLBCL patients (P = .01 and P = .004, respectively), and the ABC type (P = .04 and P = .008, respectively) but not the germinal center B‐cell type. Both CD47high and SIRPαhigh yielded a constant independent prognostic value for OS and PFS in multivariate analysis (hazard ratio [HR], 2.93; 95% confidence interval [CI], 1.20‐7.43; P = .02; and HR, 2.87; 95% CI, 1.42‐5.85; P = .003, respectively). To the best of our knowledge, this is the first study to report that combinatorial CD47 and SIRPα expression is a potential independent prognostic factor for DLBCL. Evaluation of CD47 and SIRPα expression could be useful before CD47 blockade therapy.

Deep-Learning 18F-FDG Uptake Classification Enables Total Metabolic Tumor Volume Estimation in Diffuse Large B-Cell Lymphoma.

Total metabolic tumor volume (TMTV), calculated from 18F-FDG PET/CT baseline studies, is a prognostic factor in diffuse large B-cell lymphoma (DLBCL) whose measurement requires the segmentation of all malignant foci throughout the body. No consensus currently exists regarding the most accurate approach for such segmentation. Further, all methods still require extensive manual input from an experienced reader. We examined whether an artificial intelligence–based method could estimate TMTV with a comparable prognostic value to TMTV measured by experts. Methods: Baseline 18F-FDG PET/CT scans of 301 DLBCL patients from the REMARC trial (NCT01122472) were retrospectively analyzed using a prototype software (PET Assisted Reporting System [PARS]). An automated whole-body high-uptake segmentation algorithm identified all 3-dimensional regions of interest (ROIs) with increased tracer uptake. The resulting ROIs were processed using a convolutional neural network trained on an independent cohort and classified as nonsuspicious or suspicious uptake. The PARS-based TMTV (TMTVPARS) was estimated as the sum of the volumes of ROIs classified as suspicious uptake. The reference TMTV (TMTVREF) was measured by 2 experienced readers using independent semiautomatic software. The TMTVPARS was compared with the TMTVREF in terms of prognostic value for progression-free survival (PFS) and overall survival (OS). Results: TMTVPARS was significantly correlated with the TMTVREF (ρ = 0.76; P < 0.001). Using PARS, an average of 24 regions per subject with increased tracer uptake was identified, and an average of 20 regions per subject was correctly identified as nonsuspicious or suspicious, yielding 85% classification accuracy, 80% sensitivity, and 88% specificity, compared with the TMTVREF region. Both TMTV results were predictive of PFS (hazard ratio, 2.3 and 2.6 for TMTVPARS and TMTVREF, respectively; P < 0.001) and OS (hazard ratio, 2.8 and 3.7 for TMTVPARS and TMTVREF, respectively; P < 0.001). Conclusion: TMTVPARS was consistent with that obtained by experts and displayed a significant prognostic value for PFS and OS in DLBCL patients. Classification of high-uptake regions using deep learning for rapidly discarding physiologic uptake may considerably simplify TMTV estimation, reduce observer variability, and facilitate the use of TMTV as a predictive factor in DLBCL patients.

Clinical Factors Affecting the Response to Osimertinib in Non-Small Cell Lung Cancer Patients with An Acquired Epidermal Growth Factor Receptor T790M Mutation: A Long-Term Survival Analysis

Osimertinib is a standard therapy for advanced non-small cell lung cancer (NSCLC) patients with anacquired epidermal growth factor receptor (EGFR) T790M mutation; however, the exploration of clinical characteristics that may affect prognosis and long-term survival is still lacking. This retrospective study aimed to provide long-term survival data and explore meaningful prognostic factors in patients treated with osimertinib. A total of 246 patients with acquired EGFR T790M mutation who were treated with osimertinib were included in this study. Progression-free survival (PFS), overall survival from osimertinib initiation (OS1), overall survival from diagnosis of advanced disease (OS), and possible prognostic clinical features were analyzed. The median PFS, OS1, and OS values were 12.17, 24.33, and 47.86months, respectively. The median PFS of patients harboring EGFR exon 19 deletions/T790M (19del/T790M) and those harboring EGFR 21 L858R/T790M were 13.27 and 9.77months (p = 0.001), respectively, while the median OS1 values were 25.03 and 18.30months (p = 0.023), respectively; however, no significant difference was found in median OS (p = 0.060). Cox regression analysis revealed that coexisting mutation type and extrathoracic metastasis affected survival (PFS, OS1). In addition, gene biopsy specimen type (tissue or blood sample) was related to PFS (p = 0.032), which implied that liquid biopsy may be an independent poor prognostic factor. This is the first reported survival analysis of osimertinib-treated Chinese patients, which indicates a median OS of 47.86months. The EGFR T790M mutation is likely to coexist with 19del and indicate longer PFS and OS1 than EGFR 21 L858R/T790M. Additionally, the extrathoracic metastasis status and biopsy specimen type might also affect the survival of patients treated with osimertinib.

Predictive value of the Lung Immune Prognostic Index (LIPI) in locally advanced non-small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) in the multicenter retrospective study.

e21076 Background: PD-L1 inhibitor, durvalumab has been approved since the PACIFIC study showed its efficacy as consolidation therapy after CCRT for locally advanced NSCLC. But predictive factor for the efficacy of CCRT on this post PACIFIC era have not been known. LIPI has been proposed as a new biomarker for the anti-PD-1 therapy of advanced NSCLC. In this study, we investigated the usefulness of LIPI as a predictive marker in multicenter cohort of patients with locally advanced NSCLC who received CCRT as initial treatment. Methods: 219 patients with available baseline LIPI were reviewed. The progression free survival (PFS) was estimated by the Kaplan-Meier method, and LIPI were calculated at baseline. Kaplan-Meier estimates of PFS and recurrence were compared using the log-rank test for trend. Multivariable analysis was conducted using the Cox and logistic regression models, respectively, adjusted for age, sex, ECOG-PS, smoking, histology, TNM stage, chemotherapy regimens, Body mass index (BMI), PD-L1 status, EGFR or ALK mutation, and baseline LIPI. Results: 62.5% (n = 137) of the patients had a good (0 factors) LIPI, while 37.5% (n = 82) had intermediate (1 factor) and poor (2 factors) LIPI respectively. In multivariable analysis, good LIPI (0 factors) were significantly associated with longer PFS (HR = 0.46, 95% CI 0.28-0.75; P &lt; 0.01) as did ECOG-PS0 (P &lt; 0.01), ≤stageIIIA (P &lt; 0.01), being treated with durvalumab after CRT (P = 0.04). There were no difference in the patient characteristics between good LIPI and intermediate/poor LIPI, significantly. Higher LIPI (1 or 2 factors) were strongly prognostic factor for recurrence after CCRT in multivariate analysis (P = 0.04), along with ECOG-PS1≤ (P &lt; 0.01), stage IIIB≤ (P &lt; 0.01). Conclusions: The good LIPI predictive value for PFS and disease control in patients treated with CCRT was confirmed. Although a strong statistical significance, we needs to be confirmed further with longer follow-up and prospective study.

Molecular features for selecting Asian metastatic melanoma patients who benefit from check-point inhibitors.

e22011 Background: There was few data for molecular characteristics of Asian metastatic melanoma patients with distinct clinical features as compared to West patients with metastatic melanoma. We conducted the molecular profiling for Asian metastatic melanoma patients with check-point inhibitors (CPIs) to find novel biomarkers to CPIs. Methods: 164 Asian patients with metastatic melanoma who received CPIs were simultaneously tested by the next generation sequencing (NGS) in tumor samples. We collected all NGS data and clinic-pathologic factors and also analyzed biomarkers for tumor response to CPIs. Results: The most common subtype was acral melanoma (39.6%) followed by cutaneous melanoma (32.3%), mucosal melanoma (26.2%) and others (1.8%). 163 pts are evaluable for efficacy; we observed 40 complete response (24.4 %), 34 confirmed partial responses (20.7%), 41 stable disease (25.0%) and 48 disease progression (29.3%). The overall confirmed response rate from the dose escalation is 45.1%. There was no significant difference of tumor response among subtypes of melanoma (p = 0.295). NRAS and TP53 mutation and NF2 deletion were significantly related to patients without the response to CPIs (p &lt; 0.05). Meanwhile, MYC and RPS6KB1 amplification were found with those with the response (p &lt; 0.05). The median progression free survival (PFS) to ICIS was 5.9 months (95% CI 3.8 - 8.05 months). Univariate analysis showed that TP53 and BRAF mutation, NF2 deletion, and BIRC2 amplification were poor prognostic values for PFS (p &lt; 0.05). Conclusions: This study reported molecular characteristics of 164 Asian patients with metastatic melanoma. The specific molecular alterations influenced on the tumor response and PFS to CPIs in those.

Artificial intelligence model to predict slow progression for advanced non-small cell lung cancer (aNSCLC) patients receiving second-line therapies.

e21596 Background: There are ongoing efforts to understand and predict exceptional response to existing cancer therapies, but few clinical characteristics of these patients are known. We trained a machine learning model using the Concerto HealthAI database of oncology EMR data that includes clinical data from CancerLinQ Discovery to predict slow progression, a proxy for exceptional response, in aNSCLC in the second line setting. Methods: We trained an XGBoost model to predict patients with a progression free survival (PFS) greater than 180 days from the start of second line therapy (index date). This cutoff approximately determines the top 20% of PFS values in our database (median PFS = 86 days). Patients were included from the study if they (1) were pathologically confirmed aNSCLC without other primary cancer diagnoses and (2) started their second-line therapy between 2013 and 2017. Patients were labeled as slow progressors if they (1) had no evidence of progression or death within 180 days of index and (2) were evaluated for progression for at least 180 days post-index. The model considered data up to 120 days prior to index date. Risk factors in the model included demographics, vitals, common labs, common medical conditions, ECOG performance status, stage, histology, prior cancer treatment patterns, prior progression/response assessments, and medication history. Feature importance was evaluated using SHapley Additive exPlanations (SHAP). Results: 2205 patients met selection criteria of the study. Of these, 420 were labeled as slow progressors. 1776 patients were used for model training and 429 were set aside for model validation. The final model was able to predict slow progression with an AUCROC of 0.75 (F-score 0.48, precision 0.39, recall 0.6). The performance compares favorably to that of a logistic regression model (0.66 AUCROC). Top features that indicated slow progression included a low number of prior progression events or regimens, absence of metastatic disease, lower stage/t-stage/ECOG, absence of COPD, previous treatment with an EGFR inhibitor, normal Alk-Phos/WBC (versus elevated), absence of tachycardia, and a normal BMI (versus low). Conclusions: Machine learning and real world-data provided promising results in predicting slow progression in aNSCLC and may be useful in discovering novel drivers of favorable response.

PIOS (Patras Immunotherapy Score) Score Is Associated with Best Overall Response, Progression-Free Survival, and Post-Immunotherapy Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC) Treated with Anti-Program Cell Death-1 (PD-1) Inhibitors.

Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic management of advanced non-small cell lung cancer (aNSCLC) over the last decade. However, there is an unmet need for clinically useful biomarkers in this patient subgroup. The aim of this study was to combine baseline clinical characteristics of aNSCLC patients, in the form of a scoring system, and to investigate its predictive and prognostic value in NSCLC patients treated with ICIs. A total of 112 patients with advanced (stages IIIA to IV) NSCLC, treated with nivolumab or pembrolizumab, were enrolled in this study. Patras Immunotherapy Score (PIOS) was developed based on four of the studied parameters (performance status (PS), body mass index (BMI), age, and lines of treatment (LOT), which were incorporated into our formula (PS × BMI/ LOT × age). PIOS score was strongly associated with best overall responses (BOR), with those patients having benefit/good response (stable disease (SD) or partial (PR) or complete response (CR), achieving a higher score compared to patients who developed progressive disease (PD) (p < 0.001). Furthermore, PIOS score was associated with progression-free survival (PFS), since high-score patients had longer PFS (p < 0.001, hazard ratio (HR) = 0.469). Moreover, PIOS was associated with post-immunotherapy overall survival (OS), with high-score patients having improved OS (log-rank p = 0.019). This study suggests that a combination of baseline parameters, which give rise to PIOS score, may predict the best response of NSCLC patients treated with anti-program cell death -1 (PD-1) monotherapy as well as it may have a potent prognostic value for PFS and post immunotherapy OS.

Real-world assessment of afatinib for patients with EGFR-positive non-small cell lung cancer.

Introduction Afatinib is used to treat patients with advanced non-small cell lung cancer (NSCLC) harboring common EGFR mutations; however, the clinicopathological factors that predict this drug's effectiveness in real-world settings remain unclear. We therefore evaluated the effectiveness of afatinib in such patients and assessed potential prognostic factors. Methods We retrospectively investigated patients with NSCLC who received first-line afatinib between July 2014 and August 2018. Variables (including sex, age, performance status, neutrophil-to-lymphocyte ratio, EGFR genotype, smoking status, clinical stage prior to treatment [stage IV vs.. postoperative recurrence], presence or absence of brain metastases, body surface area, any afatinib dose reductions, and afatinib starting dose [40 vs.. 20 or 30 mg]) were subjected to a Cox proportional hazards regression model to estimate progression-free survival (PFS). Results Forty-eight patients with a median age of 67 years were included; the objective response rate was 62.5% (30 patients). The median PFS was 14.1 months; the PFS periods were 11.8 and 15.9 months for patients receiving 40 mg versus 20-30 mg of afatinib (P = 0.41), respectively, and were 14.5 and 13.8 months for patients who required afatinib dose reduction and those who did not, respectively (P = 0.80). The PFS tended to be longer in patients without brain metastases (albeit not significantly). Ultimately, no significant predictive values for PFS were identified. Conclusions Afatinib is effective for patients with NSCLC harboring common EGFR mutations irrespective of their clinicopathological backgrounds. A direct comparison of afatinib and osimertinib in treatment-naïve patients is warranted to determine the optimal standard of care.

Efficacy and Safety of Proposed Bevacizumab Biosimilar BE1040V in Patients With Metastatic Colorectal Cancer: A Phase III, Randomized, Double-blind, Noninferiority Clinical Trial

PurposeThe purpose of this study was to compare the efficacy and safety of a proposed bevacizumab biosimilar to those of the reference product in patients with metastatic colorectal cancer (mCRC). MethodsThis Phase III, multicenter, randomized, double-blind (patient- and assessor-blind), active-controlled, 2-armed, parallel-group, noninferiority trial was conducted in patients with histologically verified colorectal cancer with evidence of at least 1 metastasis. Patients with mCRC were randomized 2:1 to receive 5 mg/kg IV of either study drug plus FOLFIRI-3 (with repeated irinotecan 100 mg/m2 60-min infusion on day 3) or the reference drug plus FOLFIRI-3 every 2 weeks for 1 year. Progression-free survival (PFS) was the primary end point, and overall survival, objective response rate, and time to treatment failure as well as safety and immunogenicity were secondary end points. The population assessable for PFS was per protocol, and the intention-to-treat population was used for sensitivity analysis. Safety was assessed based on reports of adverse events, laboratory test results, and vital sign measurements. FindingsA total of 126 patients were enrolled; PFS values in the biosimilar and reference arms were 232 days (7.7 months) and 210 days (7 months), respectively (P = 0.47). The hazard ratio of the biosimilar arm versus the reference arm was 0.79 in the per-protocol population (90% CI, 0.46–1.35; P = 0.47). The upper limit for the 2-sided 90% CI was lower than the margin of 1.44, indicating that the biosimilar drug was noninferior to the reference drug. The hazard ratio for overall survival in the intent-to-treat population was 0.99 (95% CI, 0.55–1.80; P = 0.99). The difference between other efficacy end points among the groups was not statistically significant. No significant difference was observed in the comparison of the two arms for safety. The antidrug antibody was positive in 1 patient in each arm. ImplicationsThe proposed biosimilar BE1040V was noninferior to the reference product in terms of efficacy in the treatment of mCRC, and tolerability was comparable between the 2 drugs. ClinicalTrials.gov identifier: NCT03288987.

Immunophenotypic Conversion between Primary and Relapse Breast Cancer and its Effects on Survival

Background: The differential expression of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor 2 (HER2) or Ki-67 between primary tumour and the recurrence has been described. We aimed to determine these changes and their prognostic implications. Patients and Methods: We retrospectively reviewed 45 breast cancer patients with relapsed biopsy that were classified into local relapse (LR) or metastatic disease (MD) groups. We analyzed the conversion rate and the value of the immunophenotype of the primary tumour and the relapse as a prognostic factor for relapse-free survival (RFS), progression-free survival (PFS) and overall survival (OS). Results: The conversion rate was 34.8% for Ki-67, 20% for ER, 20% for PR, and 15.6% for HER2. For the LR group, the RFS was 71.9 months and the OS was 141.6 months, without statistical differences according to the immunophenotype of the primary or the relapsed biopsy. For the MD group, the PFS was 20.8 months. According to immunophenotype of the relapse, the PFS were ER+ 24.7 months vs. ER– 9.3 months; PR+ 25.1 months vs. PR– 12.7 months without statistical differences according to HER2 or Ki67. The OS for MD group was 54.4 months without statistical differences according to immunophenotype. Conclusion: The characteristics of breast cancer can change over the time. Variations of the ER or PR status in MD group have prognostic value for PFS. To perform a biopsy of relapses is warranted in order to establish the prognostic of the current disease, and probably a more accurate treatment.

Prognostic value of 18F-FDG PET/CT imaging and related factors for patients with classic Hodgkin lymphoma before or after autologous stem cell transplantation

Objective To assess the predictive value of 18F-fluorodeoxyglucose (FDG) PET/CT imaging and relevant factors in the prognosis of patients with classic Hodgkin lymphoma (cHL) before or after autologous stem cell transplantation (ASCT). Methods From January 2008 to June 2017, 55 cHL patients (28 males, 27 females; age: (28.8±9.6) years) confirmed by pathology in Shanghai General Hospital were retrospectively included. 18F-FDG PET/CT imaging was performed before ASCT in 43 cases and after ASCT in 34 cases (22 patients underwent the imaging both before and after ASCT). Patients were divided into positive group (≥4) and negative group (<4) according to 18F-FDG PET/CT imaging results using Deauville 5-point scale. The predictive value of relevant factors in the prognosis was evaluated with progression-free survival (PFS) and overall survival (OS) using Kaplan-Meier survival analysis and log-rank test. Hazard ratio (HR) was calculated by Cox regression model. Results Of 55 cHL patients, 29 (53%) had a progression of disease after a median follow-up of 8 months, and 11 (20%) patients died after a median follow-up of 29.5 months, with the 3-year PFS rate of 46.4% and OS rate of 84.5%. Significant differences of PFS rate were found between patients with or without B symptoms, between patients with or without large mediastinal mass, between patients with international prognostic score (IPS) of 0-2 and those with IPS of 3-7, among patients with different effect of salvage chemotherapy (complete remission (CR), partial remission (PR) + stable disease (SD), progressive disease (PD)), and between patients with negative or positive PET/CT imaging results before or after ASCT (χ2 values: 5.52-20.01, HR: 2.21(95% CI: 1.56-3.12)-5.51(95% CI: 1.86-16.33), all P<0.05). B symptoms and large mediastinal mass were also prognostic factors for OS rate (HR: 5.28(95% CI: 1.14-24.51) and 4.27(95% CI: 1.24-14.79), both P<0.05). The combination of 18F-FDG PET/CT imaging before and after ASCT was statistically significant for predicting PFS (χ2=11.28, P<0.01). Multivariate survival analysis showed that the risk of progression in patients with positive PET/CT results after ASCT was significantly higher than those with negative results (HR=6.20, P<0.01), and the risk of death in patients with B symptoms was significantly higher than those without B symptoms (HR=5.28, P<0.05). Conclusion 18F-FDG PET/CT imaging results after ASCT have important values for predicting PFS in cHL patients after ASCT, and B symptoms can be used as an important prognostic indicator of OS after ASCT. Key words: Lymphoma; Stem Cells; Transplantation, autologous; Positron-emission tomography; Tomography, X-ray computed; Deoxyglucose