Predictor Of PFS Research Articles

Prognostic Value of a Novel Nomogram Combining 18F-Alfatide PET/CT with Inflammatory Biomarkers in Patients with Advanced NSCLC Receiving Bevacizumab Combination Therapy

Imaging of angiogenesis based on 18F-alfatide PET/CT could predict the tumor sensitivity to CCRT and antiangiogenic therapy. We attempted to evaluate its predictive role in advanced NSCLC patients treated by bevacizumab and chemotherapy. Serum inflammatory biomarkers, representing the systemic status, are shown to have complicated relationships with tumor angiogenesis. A novel nomogram integrating molecular imaging with 18F-alfatide PET/CT and serum inflammation biomarkers was built to explore its predictive role. Patients with advanced NSCLC underwent 18F-RGD PET/CT examination and serum biochemistry test before the start of bevacizumab combination therapy. PET/CT parameters including maximum and mean standard uptake values (SUVmax/SUVmean), peak standard uptake values (SUVpeak) and metabolic tumor volume (MTV) of contoured tumor lesions and inflammation biomarkers including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were systemic collected. Receiver-operating characteristic (ROC) curve analysis was used to determine accuracy in predicting response. Univariate and multivariate Cox models were used for Progression (PFS) analyses to determine the independent prognosis factors. Nomograms were then established for predicting prognosis. 22 patients with 40 measurable lesions met the inclusion criteria in present study. The median progression-free survival (mPFS) was 3 months (95% confidence interval, 0.37-10.2). The SUVmax, SUVmean, SUVpeak and MTV were significantly higher in responding tumors than in non-responding tumors (p = 0.001, p = 0.007, p = 0.005, p = 0.003, respectively). The area under the ROC curve (AUC) were 0.7294 (p = 0.038), 0.7061 (p = 0.626), 0.7419 (p = 0.029) and 0.7957 (p = 0.008) for SUVmax, SUVmean, SUVpeak and MTV, respectively. Multivariate analysis revealed that SUVmax, MTV and LMR were independent predictors of PFS (p = 0.022, p = 0.032, and p = 0.009, respectively). The nomogram for PFS was established by combining all significant markers. The concordance index (C-index) for PFS was 0.861 (95%CI 0.828-0.894), which showed superior discriminatory power. 18F-RGD uptake on PET/CT imaging can effectively predict the response of bevacizumab combination therapy. The proposed nomogram based on molecular imaging with 18F-RGD PET/CT and serum inflammatory biomarkers with superior prediction ability could provide guidance for treatment decisions.

Stereotactic Radiotherapy for Oligometastatic and Oligoprogressive Solid Tumors: Who Benefits?

Recent prospective studies suggest a survival benefit to surgery or stereotactic ablative radiotherapy (SABR) for oligometastatic (OM) solid tumors. SABR is also increasingly used for oligoprogressive (OP) disease, wherein limited metastatic sites progress on otherwise effective systemic therapy. However, data to define specific benefitting patient subgroups are lacking. We retrospectively analyzed outcomes following SABR for OM and OP solid tumors to identify promising patient subgroups for future prospective studies. We retrospectively analyzed all patients treated at a single institution with SABR for OM and OP solid tumors between March 2007-Sept 2018. OP was defined as limited metastatic progression while on otherwise effective systemic therapy, and OM was defined as limited metastases in which all metastatic sites were addressed with radiation and/or surgery. For OP patients, the line of systemic therapy at progression was documented. Disease free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The log-rank method was used to compare outcomes between groups. Toxicity was graded using CTCAE v 5.0. 78 patients completing 89 courses of SABR were identified, 57 targeting OM tumors and 32 targeting OP tumors. Median age was 64 years (range: 27-95) and median follow up was 25.4 months (range: 1.2-79.7). Histologic subtypes include NSCLC (20), colorectal (n = 15), breast (n = 10), sarcoma (n = 9), melanoma (n = 6), prostate (n = 5), renal cell (n = 5), and other (n = 22). SABR was delivered to a median of 50 Gy (range: 16-60 Gy) over 5 fractions (range: 2-5) to a median of one tumor (range:1-6). Among oligoprogressive cases, systemic therapy at OP included chemotherapy (n = 12), targeted therapy (n = 13), immunotherapy (n = 4), and endocrine therapy (n = 3). Metastatic targets included lung (n = 47), liver (n = 17), bone (n = 18), and other (n = 7). Two-year OS was 71% for OM and 80% for OP patients, and 2-year PFS was 26% for OM and 21% for OP patients. Three-year PFS for the entire cohort was 20%. Ten patients had sustained PFS beyond 3 years (5 OM and 5 OP), including patients with NSCLC (n = 2), melanoma (n = 2), colon (n = 2), sarcoma, kidney, breast, and skin. Patients with long-term PFS predominantly underwent SABR to lung metastases (n = 7). No significant predictors of PFS or were identified. Grade 3+ toxicity included grade 3 pneumonitis (n = 1) and grade 5 bowel perforation (n = 1). OM and OP solid tumor patients have excellent outcomes, with 20% 3-year PFS in this cohort with limited toxicity. However, predictors of long-term disease control remain elusive. In our cohort, select patients with a range of solid tumor types and prior therapies had extended disease control. Well-designed, prospective studies in focused tumor settings are necessary to better define which patients will benefit from aggressive local therapies.

Is the duration of castration resistance predictive for sequential treatment responses in the metastatic castration-resistant prostate cancer setting?

Prostate cancer is the second leading cause of cancer death in men. Androgen deprivation therapy (ADT) has been the primary therapeutic approach for treatment of prostate cancer. However,nearly all patients develop the castration-resistant disease . We evaluated real-world data with abiraterone and enzalutamide treatment. By this data, we aimed to analyze whether that prior short response to ADT could predict response to subsequent therapy with androgen receptor axis targeted agent (ARATA). We collected data from two cancer centers, 151 consecutive patients with treated abiraterone or enzalutamide in the first line of metastatic castration resistant prostat cancer (mCRPC) setting were included. The patients who received docetaxel in castration naive setting is also included. Time to castration resistance (TTCR) was defined as the duration from the initial to failure of primary ADT. Patients with treated ARATA were divided into two groups according to the time to castration resistance (TTCR). Patients who became resistant to ADT up to one year had a median PFS of 6.6 months, compared to median PFS of 13.3 months for patients who responded ADT for more than 1 year. (p = 0.002). In the post-docetaxel setting, median PFS is 12.6 months of patients with treated ARATA who had TTCR for more than one year, and median PFS is 6.6 months in those who had TTCR less than one year (p = 0.007).Univariate and multivariate analyses were performed to determine the clinical factors on ARATA outcomes. Eastern Cooperative Oncology Group (ECOG) performance status(PS), median prostate-specific antigen(PSA) and time to CRPC were significantly predicted outcomes of ARATA on multivariate analysis. TTCR is also a predictor for PFS of the patients who were treated ARATA both whole cohort and post-docetaxel.

Abstract 3201: Molecular subtype specific biomarkers improve prediction of temozolomide therapy in low grade glioma

Abstract Introduction: Based on IDH mutation and 1p/19q codeletion, low grade glioma (LGG) could be classified into three groups with different prognosis : IDHmut-codel, IDHmut-non-codel and IDHwt,. Temozolomide (TMZ) is commonly used to reduce LGG recurrence and mortality. However, increasing studies have demonstrated MGMT promoter methylation status could not predict the therapeutic effect of TMZ in the different molecular subtypes of LGG. Therefore, promising molecular markers of TMZ chemotherapy in each subgroup is in urgent need. Methods: LGG data sets containing information of mutations and copy number aberrations (CNVs), as well as clinical records and treatment history were retrieved form The Cancer Genome Atlas. TMZ treated patients with intact PFS/OS information were selected(n=256). Kaplan-Meier and Cox's proportional hazard model were used to estimating survival and selecting predictive molecular makersin these TMZ-treated LGG.The Chinese Glioma Genome Atlas (CGGA) was used as independent validation data. Results: These patients were classified into IDHmut-codel (n=69), IDHmut-non-codel (n=127) and IDHwt (n=60) subgroups. MGMT promoter is methylated (MGMTpo-m) in 99% patients with IDHmut-codel .And the status of MGMT promoter methylation was not correlated with either PFS or OS in both IDHmut-non-codel and IDHwt cohorts. Based on the cox regression analysis, PIK3CA, mutated in 20% IDHmut-codel patients, significantly correlated with PFS (p=0.03) and OS (p=0.02) in this cohort. TTN obviously correlated with PFS (p=0.01) and OS (p < 0.01) in IDHmut-non-codel cohort. C9orf53, homozygous deletion in 40% IDHwt patients, significantly correlated with PFS (p=0.03) and OS (p < 0.01) in IDHwt cohort. Multivariate cox regression confirmed these three genes were independent predictors in each cohort. Notably, the combination of PIK3CA with TTN mutations (marked as PIK3CA/TTN) exhibited striking correlation with PFS (p < 0.01) and OS (p < 0.01) in the IDHmut cohort (IDHmut-codel and IDHmut-non-codel cohorts), and multivariate cox regression confirmed it was also an independent predictor of PFS (p < 0.01) and OS (p < 0.01). The predictive effect of PIK3CA/TTN was validated in an independent dataset CGGA. OS was significantly higher in PIK3CA/TTN patients (p = 0.04) and multivariate cox regression confirmed its independent predictive effect (p=0.04). Conclusion: Although MGMT methylation status is considered as the predictive markers for TMZ chemotherapy in LGG. In this work, we proved it could not predict TMZ efficacy in each molecular subtypes of LGG . However, PIK3CA, TTN, PIK3CA/TTN and C9orf53 were identified as promising molecular markers of TMZ in different subtypes of LGG: PIK3CA for IDHmut-codel, TTN for IDHmut-noncodel, C9orf53 for IDHwt subtype, and PIK3CA/TTN mutation for all IDH mutant LGG. Citation Format: Feng Jia, Feilong Zhao, Xiaoyan Zhang, Jiao Feng, Tonghui Ma, Tao Lv, Xiaohua Zhang. Molecular subtype specific biomarkers improve prediction of temozolomide therapy in low grade glioma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3201.

Early serum TARC reduction predicts prognosis in advanced-stage Hodgkin lymphoma patients treated with a PET-adapted strategy.

Among patients with advanced-stage classical Hodgkin lymphoma (cHL) receiving ABVD chemotherapy, PET performed after the first two treatment cycles (PET-2) has prognostic value. However, 15% of patients with a negative PET-2 will experience treatment failure. Here we prospectively evaluated serum thymus and activation-regulated chemokine (TARC) levels, to improve risk assessment in patients treated according to HD0607 PET-driven trial (#NCT00795613). In 266 patients with available serum samples, who have agreed to participate in a sub-study for assessment of the role of TARC monitoring, serum TARC levels were measured at baseline and at time of PET-2 by commercially available ELISA test kits. The primary end-point was to evaluate the association between TARC after 2 ABVD cycles and PFS. Median TARC-2 values were significantly higher in PET-2-positive patients compared to PET-2-negative patients (P = .001), and in patients with treatment failure compared to those in continuous CR (P = .01). The 4-year PFS significantly differed between patients with TARC-2 >800 pg/mL vs ≤800 pg/mL (64% vs 86%, P = .0001). Moreover, among PET-2-negative patients, elevated TARC-2 identified those with a worse prognosis (74% vs 89%; P = .01). In multivariable analysis, TARC-2 >800 pg/mL was a significant independent predictor of PFS in the whole study population (HR 2.39, P = .004) and among the PET-2-negative patients (HR 2.49, P = .02). In conclusion, our results indicate that TARC-2 serum levels above 800 pg/mL suggest the need for a stringent follow-up in PET-2-negative patients, and the evaluation of new drugs in PET-2-positive, who will likely fail to respond to intensification with escalated BEACOPP.

NUTRITIONAL DERANGEMENTS IN ADVANCED NON-SMALL CELL LUNG CANCER PATIENTS: PREVALENCE AND IMPACT ON TREATMENT OUTCOME

To evaluate the nutritional status and its correlation with outcome in advanced (A) non-small cell lung cancer (NSCLC) pts. A-NSCLC pts treated at AOUI of Verona (2016-2018) received nutritional counseling by a skilled dietitian. Nutritional Risk Screening (NRS) 2002 was used to assess nutritional risk. Bilateral psoas major muscles were measured at L3 vertebral level with routine staging-computed tomography (CT). Changes in psoas muscles observed in subsequent scans were evaluated using the Wilcoxon signed-rank test. Data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox model. Data from 38 pts were gathered, with a median follow-up of 21 months (range 1-197). At baseline, only 18.4% of pts were underweight. The majority (65.8%) were at risk of malnutrition (NRS≥3). At multivariate analysis, stage (HR 4.99, p=0.04), performance status (HR 4.99, p=0.007) and NRS (HR 7.61, p=0.01) were significant independent predictors for PFS. Pts with baseline NRS≤3 had significantly longer 1-year PFS (58.6% vs 16.7%, p=0.04) and 2-year OS (90.6% vs 68.3%, p=0.03) and a better ORR than those with NRS>3 (66.7% vs 21.4%). In 16 pts treated with immunotherapy, loss in psoas muscle mass (p=0.01) correlated with worse ORR, PFS and, OS, although differences did not reach a statistical significance due to the limited sample. Malnutrition has a detrimental impact on ORR, PFS and, OS in A-NSCLC. Particularly, in pts treated with immunotherapy, muscle mass wasting seems to affect efficacy outcome, suggesting a potential interaction between immunological and nutritional parameters.

P-271 Meta-analyses on mutation status concordance between tumor tissue and circulating tumor DNA and prognostic value of ctDNA in pancreatic cancer

Liquid biopsy is a promising method of diagnostics in pancreatic cancer (PC). Concordance of mutational status between tumor tissue and circulating tumor DNA (ctDNA) and the prognostic significance of the latter have been actively studied in recent years but results are heterogeneous. We carried out a systematic review and meta-analyses to address these issues. PubMed, ASCO and ESMO databases were searched to identify studies that have been published until February 2020. Inclusion criteria for publications were the following: more than 10 participants enrolled in the study, presence of the data concerning concordance of mutations identified in paired tumor and blood samples; for articles on prognostic significance – presence of HR and 95% CI for PFS and OS. Random effects were used for analyses due to potential heterogeneity of the studies. Meta-analyses were performed using Review Manager (RevMan), version 5.3. 16 studies including 549 patients were enrolled to assess mutational status concordance. The data of these studies were significantly homogeneous (р=0.31, I2=12%). Our results showed that the mutational status of ctDNA and tumor tissue was significantly different (16%, HR 0.84, 95% CI 0.78-0.90, р< 0.00001). Analysis of ctDNA prognostic significance included 17 studies, 5 of which were dedicated to resectable PC. Meta-analysis of the studies evaluating the importance of ctDNA at any stage of disease showed that detection of ctDNA before treatment adversely affected OS (HR 2.21, 95% CI 1.35-3.33, р=0.001) (I2=84%, р< 0.00001). Presence of ctDNA both before and after surgery was a negative predictor of PFS (HR 2.32, 95% CI 1.54-3.5, р< 0.0001; I2=0%, р=0.47) and OS (HR 2.01, 95% CI 1.12-3.63, р=0.02; I2=51%, р=0.08). Patients with undetectable ctDNA after surgery also had better PFS (HR 3.06, 95% CI 1.63-5.76, р=0.0005; I2=45%, р=0.18) and OS (ОP 3.39, 95% CI 2.12-5.44, р< 0.00001; I2=0%, р=0.78) compared with patients with detectable ctDNA. The possible discordance of the mutational status between ctDNA and the primary tumor has been shown. The detection of ctDNA in the blood of patients was a negative prognostic factor in resectable and advanced PC.

A new prognostic model for high-grade appendiceal mucinous neoplasms with peritoneal carcinomatosis.

e16718 Background: Peritoneal carcinomatosis of appendiceal origin (PCAO) is a rare malignancy accounting for less than 1% of all cancers. High-grade appendiceal mucinous neoplasms (HAMN) have a poor prognosis and are often treated with cytoreductive surgery (CRS), with hyperthermic intraperitoneal chemotherapy (HIPEC) followed by adjuvant systemic chemotherapy (ASC). Peritoneal cancer index (PCI) and completeness of cytoreduction score (CCR) are useful prognostic tools in patients with PCAO undergoing CRS/HIPEC. However, neither PCI nor CCR take response to ASC into account. Therefore, we propose an enhanced prognostic scoring system (tumor response index, TRI) that incorporates response to ASC as assessed at the completion of treatment. Methods: We retrospectively reviewed the charts of patients with PCAO who received care at the Van Elslander Cancer Center between January 2011 until December 2018. All patients with HAMN who underwent CRS/HIPEC followed by ASC were included. TRI was assessed by comparing the patients' performance status, tumor markers and imaging at the completion of ASC to those prior to the initiation of ASC. A competing risk model, Kaplan-Meier analysis and multivariate Cox regression analysis were used to estimate correlations between TRI and clinical outcomes (PFS and OS). TRI was also compared to PCI and CCR using the Akaike’s Information Criteria (AIC). Results: A total of 84 charts were reviewed. Patients were divided into groups based on their TRI score. The median age was 57 years with 55% females and 85% Caucasians. Approximately 20% of patients had signet-ring features. The most common ASC regimen used was a combination of 5-fluorouracil, oxaliplatin (FOLFOX) and bevacizumab (65%). The table depicts the median PFS and OS of each TRI group. Lower TRI was associated with significantly better PFS and OS. For all outcomes, AIC was substantially reduced by adding TRI to PCI and CCR, suggesting that TRI is a better predictor of PFS and OS. Conclusions: This study proposes TRI as an effective prognostic tool in patients with PCAO and HAMN after CRS/HIPEC/ASC. [Table: see text]

TCR clonality and Treg frequency as predictors of outcome in stage III NSCLC treated with durvalumab.

3050 Background: Novel blood-based biomarkers evaluating T-cell receptor (TCR) clonality as well as the frequency/activation of immune populations hold significant potential for predicting response and elucidating the biology of anti-tumor immunity in stage 3 NSCLC treated with durvalumab. In this study, we sought to characterize clinical and immunologic predictors of durable response to therapy with a specific focus on TCR clonality and peripheral immune populations. Methods: Stage 3 NSCLC patients undergoing chemoradiation (CRT) and durvalumab were prospectively recruited and underwent baseline and serial blood collections. TCR repertoire analysis was performed on cfDNA using hybrid-capture TCR sequencing and TCR diversity estimated using Shannon’s entropy index. Viably preserved peripheral blood mononuclear cells (PBMC) were analyzed by high-dimensional flow cytometry using validated panels to evaluate T/B/NK-cell, Treg and myeloid populations. Correlations between cell populations were examined using linear and cox regression. Results: 134 stage 3 NSCLC patients who received durvalumab had a median PFS was 15.4 months, with worse PFS in patients with PD-L1 1-49% (HR 2.4, p = 0.03) and PD-L1 &lt; 1% (HR 2.6, p = 0.03). Smoking and EGFR/ALK mutations were not predictors of PFS. Immune profiling was performed in a pilot of 19 patients. Baseline TCR diversity did not associate with clinical factors or outcome. However, lack of clonal expansion after CRT indicated by a higher Shannon’s index was significantly associated with increased frequency of Tregs after durvalumab (p &lt; 0.05). In turn, this elevation in Tregs was associated with significantly reduced PFS in EGFR/ALK wt patients (p = 0.03) and a trend towards reduced PFS in the overall cohort (HR 5.2, p = 0.1). Conclusions: Clonal expansion of T cells after CRT may influence the likelihood of an anti-tumor immune response following PD-L1 blockade in stage 3 NSCLC. Similarly, expansion of peripheral Treg populations is associated with increased likelihood of disease recurrence. Further characterization of TCR clonality, minimal residual disease and T cell subpopulations using serially collected blood is ongoing.

Baseline FDG-PET/CT detects bone marrow involvement in follicular lymphoma and provides relevant prognostic information

AbstractIn follicular lymphoma (FL), detection of bone marrow (BM) involvement (BMI) by 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) improves the accuracy of staging vs BM biopsy (BMB) alone. Our objective was to determine the diagnostic utility of PET for BMI FL and the prognostic value of BMI by PET (positive PET result [PET+]). Records of patients (2002-2016) with PET and BMB at the time of initial treatment were reviewed. BMI was identified by positive BMB result (BMB+) and/or unifocal or multifocal BM FDG uptake on blindly reviewed PET scans with no corresponding CT abnormality (PET+). Among 261 patients, BMI was diagnosed in 78 patients (29.9%) by PET+, in 81 patients (31.0%) by BMB+, and in 113 patients (43.3%) by either PET+ or BMB+. PET+ upstaged 24 patients to stage IV, including 10 from stages I or II to stage IV. Median duration of follow-up was 6.0 years (range, 0-16.6 years). In univariate analysis, a high Follicular Lymphoma International Prognosis Index (FLIPI) score, PET+, and BMB+ correlated with shorter progression-free survival (PFS; all P ≤ .03), and high FLIPI, PET+, and combined PET+ and BMB+ with shorter overall survival (OS; all P ≤ .01). In multivariate analysis, PET+ was the only independent predictor of PFS, whereas high FLIPI score and PET+ predicted OS (P ≤ .03). Combined PET and BMB identify BMI more accurately than either BMB or PET alone, but BMB rarely adds critical information. For patients initiating treatment of FL, identification of BMI by PET is predictive of PFS and OS.

Chemoradiotherapy response prediction model by proteomic expressional profiling in patients with locally advanced cervical cancer

ObjectiveResistance to chemo-radiation therapy is a substantial obstacle that compromises treatment of advanced cervical cancer. The objective of this study was to investigate if a proteomic panel associated with radioresistance could predict survival of patients with locally advanced cervical cancer. MethodsA total of 181 frozen tissue samples were prospectively obtained from patients with locally advanced cervical cancer before chemoradiation. Expression levels of 22 total and phosphorylated proteins were evaluated using well-based reverse phase protein arrays. Selected proteins were validated with western blotting analysis and immunohistochemistry. Performances of models were internally and externally validated. ResultsUnsupervised clustering stratified patients into three major groups with different overall survival (OS, P = 0.001) and progression-free survival (PFS, P = 0.003) based on detection of BCL2, HER2, CD133, CAIX, and ERCC1. Reverse-phase protein array results significantly correlated with western blotting results (R2 = 0.856). The C-index of model was higher than clinical model in the prediction of OS (C-index: 0.86 and 0.62, respectively) and PFS (C-index: 0.82 and 0.64, respectively). The Kaplan-Meier survival curve showed a dose-dependent prognostic significance of risk score for PFS and OS. Multivariable Cox proportional hazard model confirmed that the risk score was an independent predictor of PFS (HR: 1.6; 95% CI: 1.4–1.9; P < 0.001) and OS (HR: 2.1; 95% CI: 1.7–2.5; P < 0.001). ConclusionA proteomic panel of BCL2, HER2, CD133, CAIX, and ERCC1 independently predicted survival in locally advanced cervical cancer patients. This prediction model can help identify chemoradiation responsive tumors and improve prediction for clinical outcome of cervical cancer patients.

Recurrence Patterns and Survival Outcomes in Chinese Patients with Surgically Treated Recurrent Ovarian Clear Cell Carcinoma: A Single Institutional Analysis of 45 Cases.

BackgroundTo evaluate the recurrence patterns and survival outcomes of surgically treated relapsed ovarian clear cell carcinoma (OCCC) patients.MethodsWe performed a comprehensive retrospective analysis of all the patients who underwent secondary debulking from 2004/10 to 2019/04.ResultsIn total, 45 eligible patients were included. 75.6% of the patients had early-stage disease and platinum-sensitive recurrence accounted for 70.5%. The median progression-free survival after primary surgery (PFS 1) was 20 months (range, 2–137). Of all, 64.4% patients had solitary recurrence and 86.7% patients had no residual disease after secondary surgery. Regarding tumor distribution, the most common site was pelvis (47.5%), followed by lymph node metastases (18.0%) and abdominal wall lesions (8.2%). For the entire population, the median disease-free survival after recurrence (PFS 2) and post-relapse survival (PRS) was 15 months (range, 0–96), and 24 months (range, 3–159), respectively. Eight patients (17.8%) had a prolonged PFS2 more than 30 months. Patients with localized relapse had better survival including PFS 2 (P=0.023), PRS (P=0.004), and overall survival (OS) (P=0.029). Patients who achieved complete resection tended to have longer PFS 2 (P=0.017). After multivariate analysis, complete resection at recurrence remained as an independent positive predictor for PFS 2 (P=0.022). The median OS was 50 months and was significantly associated with platinum response (P=0.003) and number of relapsed lesions (P=0.002).ConclusionA high rate of pelvic recurrence was noted in this population. Patients with focal recurrence had a favorable prognosis. Complete resection at secondary debulking proved to be an independent predictor for disease-free survival.

Evaluation of nutritional status in non-small-cell lung cancer: screening, assessment and correlation with treatment outcome

BackgroundNutritional derangements are common hallmarks of non-small-cell lung cancer (NSCLC). Nevertheless, their early detection is overlooked in clinical routine. This study aimed to evaluate nutritional status and its correlation with outcome in NSCLC patients.MethodsData regarding NSCLC patients undergoing nutritional evaluation were prospectively collected (May 2016–October 2018). Nutritional risk was assessed by Nutritional Risk Screening 2002 (NRS-2002). Bilateral psoas major muscles were measured at L3 vertebrae level with routine staging-computed tomography and changes were evaluated using Wilcoxon signed-rank test. Clinico-pathological and nutritional data were correlated to progression-free/overall survival (PFS/OS) and response rate (ORR) using a Cox and logistic regression model. Kaplan–Meier curves were compared with log-rank test.ResultsThirty-eight patients were included. The majority (65.8%) of them were at nutritional risk (NRS-2002 ≥3). At multivariate analysis for patients with advanced disease, age (HR 2.44, p=0.05), performance status (HR 2.48, p=0.043) and NRS-2002 (HR 1.74, p=0.001) were significant independent predictors for PFS and weight loss (HR 1.07, p=0.008) for OS. Patients with baseline NRS-2002 <3 had significantly longer 1-year PFS (85.7% vs 19.4%, p=0.02) and higher ORR (66.7% vs 21.4%) than those with NRS-2002 ≥3. An explorative evaluation demonstrated that NRS-2002 score significantly decreased after nutritional intervention (p=0.001) for 3 months.ConclusionBaseline nutritional risk represents a prognostic factor in NSCLC. Nutritional counselling should be applied as a fundamental tool to improve nutritional risk in a short period, ameliorating patients’ outcome.

Elevated baseline serum PD-1 or PD-L1 predicts poor outcome of PD-1 inhibition therapy in metastatic melanoma

Programmed cell death protein 1 (PD-1) checkpoint inhibition has recently advanced to one of the most effective treatment strategies in melanoma. Nevertheless, a considerable proportion of patients show upfront therapy resistance and baseline predictive biomarkers of treatment outcome are scarce. In this study we quantified PD-1 and programmed death-ligand 1 (PD-L1) in baseline sera from melanoma patients in relation to therapy response and survival. Sera taken at therapy baseline from a total of 222 metastatic melanoma patients (two retrospectively selected monocentric discovery cohorts, n= 130; one prospectively collected multicentric validation cohort, n= 92) and from 38 healthy controls were analyzed for PD-1 and PD-L1 concentration by sandwich enzyme-linked immunosorbent assay. Melanoma patients showed higher serum concentrations of PD-1 (P= 0.0054) and PD-L1 (P < 0.0001) than healthy controls. Elevated serum PD-1 and PD-L1 levels at treatment baseline were associated with an impaired best overall response (BOR) to anti-PD-1 (P= 0.014, P= 0.041), but not to BRAF inhibition therapy. Baseline PD-1 and PD-L1 serum levels correlated with progression-free (PFS; P= 0.0081, P= 0.053) and overall survival (OS; P= 0.055, P=0.0062) in patients who received anti-PD-1 therapy, but not in patients treated with BRAF inhibitors. By combining both markers, we obtained a strong discrimination between favorable and poor outcome of anti-PD-1 therapy, with elevated baseline serum levels of PD-1 and/or PD-L1 associated with an impaired BOR (P= 0.037), PFS (P= 0.048), and OS (P= 0.0098). This PD-1/PD-L1 combination serum biomarker was confirmed in an independent multicenter validation set of serum samples prospectively collected at baseline of PD-1 inhibition (BOR, P= 0.019; PFS, P= 0.038; OS, P= 0.022). Multivariable Cox regression demonstrated serum PD-1/PD-L1 as an independent predictor of PFS (P= 0.010) and OS (P= 0.003) in patients treated with PD-1 inhibitors. Our findings indicate PD-1 and PD-L1 as useful serum biomarkers to predict the outcome of PD-1 inhibition therapy in melanoma patients and to select patients for PD-1-based versus BRAF-based therapy strategies.

Predictors of progression free survival, overall survival and early cessation of chemotherapy in women with potentially platinum sensitive (PPS) recurrent ovarian cancer (ROC) starting third or subsequent line(≥3) chemotherapy – The GCIG symptom benefit study (SBS)

BackgroundPotentially platinum sensitive recurrent ovarian cancer (PPS ROC) is defined by a platinum-free interval of >6 months, and usually treated with platinum-based chemotherapy with variable response and benefit in women who have had 3 or more lines of chemotherapy(≥3). We identified baseline characteristics (health-related quality of life[HRQL] and clinicopathological factors), associated with PFS, OS and early progression (within 8 weeks). The goal is to improve patient selection for chemotherapy based on a nomogram predicting PFS. MethodsHRQL was assessed with EORTC QLQ-C30/QLQ-OV28. Associations with PFS and OS were assessed with Cox proportional hazards regression. Variables significant in univariable analysis were included in multivariable analyses using backward elimination to select those significant. Associations with stopping chemotherapy early were assessed with logistic regression. Results378 women were enrolled, with median(m)OS and PFS of 16.6 months and 5.3 months, respectively. The majority had ECOGPS 0–1. Chemotherapy was stopped early in 45/378 participants (12%); with mOS 3.4 months (95% CI: 1.7–7.2). Physical function(PF), role function(RF), cognitive function(CF), social function(SF), Global Health Status(GHS) and abdominal/GI symptoms(AGIS) were significant univariable predictors of PFS(p < 0.030). SF remained significant after adjusting for clinicopathological factors; p = 0.03. PF, RF, CF, SF, GHS and AGIS were significant univariable predictors of OS (p < 0.007); PF, RF, SF and GHS remained significant predictors of OS in multivariable models; p < 0.007. Poor baseline PF and GHS were significant univariable predictors of stopping chemotherapy early (p < 0.007) but neither remained significant after adjusting for clinicopathological factors. ConclusionBaseline HRQL is simple to measure, is predictive of PFS and OS and when used in conjunction with clinicopathological prognostic factors, can assist with clinical decision making and treatment recommendations for women with PPSROC≥3.

The prognostic role of circulating CD8+ T cell proliferation in patients with untreated extensive stage small cell lung cancer

BackgroundImmunosuppression caused by tumorigenesis may promote tumor progress and invasion. Here, we investigated whether the characteristics of circulating T lymphocyte subtypes in patients with extensive small cell lung cancer (ED-SCLC) can be used as an alternative marker of tumor progression.MethodsThis study included 36 newly diagnosed ED-SCLC patients before treatment and the patients were followed up. 22 age and sex-matched healthy volunteers were selected as control. The percentages and proliferation potential of T lymphocyte subpopulations from peripheral blood were measured.ResultsCD4+ CD25+ Foxp3+ regulatory T cells (Tregs) were elevated in ED-SCLC patients compared with healthy controls (p = 0.0083). In contrast, the percentages of CD3+ and CD3+CD4+ T cells were significantly lower in SCLC patients (p < 0.001; p = 0.0014). The proliferation (%divided) of CD8+ T cells of SCLC patients was suppressed compared with healthy controls (p = 0.0058), but not of CD4+ T cells (p = 0.1611). Multivariate analyses showed that the %divided of CD8+ T cells is an independent predictor for PFS (HR: 4.342, 95% CI 1.324–14.245; p = 0.015). The percentages of peripheral Tregs and the degree of chemotherapy or radiotherapy induced lymphopenia negatively correlated with the proliferation of CD8+ T cells (p = 0.0225, r = − 0.379; p = 0.0003, r = − 0.464).ConclusionThe present study indicates that SCLC patients have impaired immunity in peripheral blood, and the proliferation potential of circulating CD8+ T cells is a significant predicator for PFS.

Ibrutinib at First Relapse for Mantle Cell Lymphoma: A United Kingdom Real World Analysis of Outcomes in 169 Patients

Ibrutinib at First Relapse for Mantle Cell Lymphoma: A United Kingdom Real World Analysis of Outcomes in 169 Patients

NIMG-35. QUANTITATIVE ESTIMATION OF PROGRESSION-FREE SURVIVAL BASED ON RADIOMICS ANALYSIS OF PREOPERATIVE MULTI-PARAMETRIC MRI IN PATIENTS WITH GLIOBLASTOMA

Abstract PURPOSE Glioblastoma managed with maximal resection and adjuvant chemoradiation has large heterogeneity at the time of tumor recurrence (progression-free survival, PFS). Upfront identification of patients with shorter than median PFS, may facilitate better personalization of treatment, such as patient stratification into clinical trials for treatment intensification and/or supportive care. The aim of the current study was to build a radiomics model that can reliably predict PFS in patients with glioblastoma at the time of initial diagnosis. EXPERIMENTAL DESIGN: A total of 66 de novo glioblastoma patients in a single institution who underwent gross total resection followed by standard adjuvant chemoradiation, were found to have pathologically confirmed recurrence. Patients who had sufficient follow-up MRI to reliably determine PFS and available pre-surgical multi-parametric MRI (mpMRI) (T1, T1Gd, T2, T2-FLAIR, DTI, DSC-MR images) were included. The patients were stratified into two classes of “short PFS (≤7 months, n=35)” and “long PFS (≥9 months, n=19)”. An extensive set of features was extracted from preoperative mpMRI scans, including shape and volumetric measures computed for different tumorous regions, and characteristics derived from histograms and gray-level co-occurrence matrix (GLCM). Predictive modeling for discrimination of patients with short from those with long PFS was performed using a 10-fold cross-validated support vector machine classifier. RESULTS An accuracy of 79.6% was achieved for prediction of short and long PFS (sensitivity=83%, specificity=74%, AUC=0.86 [95%CI: 0.76–0.96]; short-PSF was considered the positive class). The patients with shorter PFS showed markedly higher cell density in the nonenhancing tumor (DTI), higher neo-angiogenesis in the enhancing tumor (DSC-MRI, T1Gd), lower water concentration in the enhancing tumor region (T2), and higher maximum enhancement (calculated by the subtraction of T1 from T1Gd) in the edema region. CONCLUSION Quantitative assessment of preoperative mpMRI provides accurate prediction of PFS for patients with glioblastoma, which can aid in personalized treatment planning.

Prediction of PFS using a dynamic assessment of ctDNA in patients with EGFR mutated NSCLC with osimertinib therapy

Abstract Background Resistance on the 1st or 2nd generation TKIs in patients with EGFR mutated NSCLC to the therapy occurs on average after 8-12 months. The most common (49-60%) resistance mechanism is the appearance of the T790M. Its determination is possible by different methods of examination: ctDNA (false-negative probability 23%) and tumor tissue (sensitivity of 88%). The appointment of osimertinib in the second line allows to increase ORR, but also PFS relative to standard chemotherapy. Methods In this study we investigated the effect on PFS by the dynamic determination of ctDNA. Included patients with metastatic EGFR-associated NSCLC, in whom, a T790M mutation was detected during treatment TKIs of 1-2 generations.Patients received osimertinib therapy 80 mg / day, daily, until progression of the disease appears. Blood test was taken to conduct a qualitative assessment of ctDNA in dynamics by the RT-PCR method, fist test was done before starting treatment, and then every 2 months. Results From August 2016 to December 2018, 22 patients were identified T790M + associated progression of EGFR + NSCLC. 81.9% (18/22) are women, 18.1% (4/22) are men. The average age is 61.2 years (50-75). 1/22 had smoking experience for more than 30 years. The molecular genetic profile in 16 is represented by ex19del, 5 L858R, 1 - a combination of rare mutations G719S + S768I. The effect of therapy was evaluated in 20/22 patients. PR and SD were registered in 9/20 (45%) and 10/20 (50%) patients, respectively. Median PFS – 18.9 months (CI 95%, 10.6 - 27.1). In 12/22 patients was observed the disappearance of ctDNA T790M + after 2 months of osimertinib therapy. PFS is 24.4 months (CI calculation is NA), in patients with no mutation detected in the second month of treatment compared with the group of patients in which the ctDNA was determined (PFS 7.6 months) (CI 95%, 3.0 –12.9) (p = 0.003). The confidence interval for one of the medians cannot be calculated the 75% percentile was 3.4 +/- 3.3 and 18.8 +/- 6.3. Conclusions The disappearance of ctDNA in plasma after 2 months of treatment with osimertinib is associated with an increase in PFS and can be considered as a predictive marker in patients with metastatic NSCLC EGFR T790M + Grant supported RUSSCO / RakFond 2018-01-YS-ECI. Legal entity responsible for the study St. Petersburg Clinical Research Center of Specialized Types of Care (Oncology). Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Prognostic impact of peripheral blood WT1-mRNA expression in patients with MDS

Few reports suggested a prognostic impact of Wilms‘Tumor-1 (WT1)-mRNA overexpression in MDS, but translation into clinical routine was hampered by limited patients numbers, differing sample sources, non-standardized methods/cut-offs. To evaluate whether WT1-mRNA expression yields additional prognostic information, we measured peripheral blood (PB) WT1-mRNA expression in 94 MDS using a standardized assay offering a validated cut-off to discriminate between normal and WT1-mRNA overexpression. Overall, 54 patients (57%) showed WT1-mRNA overexpression, while 40 patients (43%) had normal WT1-mRNA expression. This enabled discrimination between MDS and both healthy controls and non-MDS cytopenias. Furthermore, WT1-mRNA expression correlated with WHO 2016 subcategories and IPSS-R as indicated by mean WT1-mRNA expression and frequency of WT1-mRNA overexpressing patients within respective subgroups. Regarding the entire group, PB WT1-mRNA expression was associated with prognosis, as those patients showing WT1-mRNA overexpression had higher risk for disease progression and AML transformation and accordingly shorter progression-free, leukemia-free and overall survival in univariate analysis. In multivariate analysis, prognostic impact of PB WT1-mRNA expression status was independent of IPSS-R and enabled more precise prediction of PFS, but not OS, within IPSS-R very low/low and intermediate risk groups. Overall, measuring PB WT1-mRNA appears valuable to support diagnostics and refine prognostication provided by the IPSS-R.