Independent Prognostic Factor For Progression-free Survival Research Articles

Absolute Lymphocyte Count Is an Independent Prognostic Factor for ER-positive HER2-negative Advanced Breast Cancer Patients Treated With CDK4/6 Inhibitors.

The aim of this study was to elucidate the clinical significance of peripheral blood biomarkers, including absolute lymphocyte count (ALC), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and C-reactive protein (CRP) in patients with estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer treated with the CDK4/6 inhibitors, abemaciclib and palbociclib. A total of 83 patients treated with fulvestrant plus abemaciclib or palbociclib were included in this study. Progression-free survival (PFS) and overall survival (OS) were compared in relation to baseline levels of ALC, NLR, PLR and CRP. The cut-off values of ALC, NLR, PLR, and CRP for PFS were determined from the receiver operating characteristic curve using the Youden index for area under the curve and set at 1,212/μl, 1.964, 170 and 0.220 mg/dl, respectively. In the abemaciclib-treated group, ALC-high patients showed significantly better PFS than ALC-low patients (p=0.0151) and multivariate analysis revealed that ALC was an independent prognostic factor for PFS (p=0.0085). In the palbociclib-treated group, there was no significant relationship between any peripheral blood biomarkers and PFS. In both treatment groups, ALC-high patients showed significantly better OS than ALC-low patients (p=0.0169 and 0.0290, respectively). Multivariate analysis revealed ALC was an independent prognostic factor for OS in both abemaciclib- and palbociclib-treated groups (p=0.0112 and 0.0202, respectively). ALC is an independent prognostic factor for estrogen receptor-positive human epidermal growth factor receptor 2-negative advanced breast cancer patients treated with the CDK4/6 inhibitors abemaciclib and palbociclib.

Radical surgery for stage IB2/IIA2 cervical cancer: A large retrospective study.

BackgroundWe aimed to evaluate survival, complications, and prognostic factors in patients with IB2/IIA2 (FIGO 2009, bulky early-stage) cervical cancer (CC) who were primarily treated with radical surgery (RS).MethodsFrom January 2011 to January 2018, patients with stage IB2/IIA2 CC who underwent RS ± adjuvant therapy were enrolled and retrospectively evaluated. Survival was estimated using the Kaplan–Meier method. Significance was determined using the log-rank test. Multivariate regression analyses were performed to determine prognostic factors.ResultsOf the 975 enrolled patients, 877 (89.9%) received adjuvant therapy. The median follow-up was 48 months, the 5-year overall survival (OS) was 85.9%, and the 5-year progression-free survival (PFS) rate was 80.8%. Multivariate analysis showed that histological type, pelvic lymph nodes, and para-aortic lymph nodes were independent prognostic factors for PFS and OS. Tumor diameter was also an independent prognostic factor with OS. Recurrent disease developed in 14.3% (140) of patients., including local, distant, and both recurrences in 55 (5.6%), 71 (7.3%), and 14 (1.4%) patients, respectively. Grade 3–4 short-term complications occurred in 196 (20.1%) patients, and long-term complications occurred in 86 (8.8%) patients. Short-term hematological complications occurred in 99 cases (10.2%). No significant differences in non-hematological complications were detected between the RS and RS + adjuvant therapy groups.ConclusionsRS followed by adjuvant therapy is a feasible and effective treatment for IB2/IIA2 CC, with a high 5-year survival rate and an acceptable incidence of complications. Positive pelvic lymph nodes and para-aortic abdominal lymph nodes significantly impact PFS and OS. Evaluation of lymph node status before surgery is important. RS is recommended for patients with negative lymph node metastasis.

Body mass index, as a novel predictor of hepatocellular carcinoma patients treated with Anti-PD-1 immunotherapy.

Immunocheckpoint inhibitors have shown significant efficacy in the treatment of hepatocellular carcinoma (HCC), but there are individual differences. The aim of this study was to explore body mass index (BMI) as a predictor of anti-PD-1 efficacy in patients with HCC. We retrospectively analyzed 101 HCC patients who treated with anti-PD-1 at Sun Yat-sen University Cancer Center from July 2018 to November 2019 and divided them into overweight (BMI > 24.9) and non-overweight (BMI ≤ 24.9) groups based on baseline BMI levels. BMI > 24.9 accounted for 22 cases (21.8%) and BMI ≤ 24.9 accounted for 79 cases (78.2%) in the study cohort. Overweight patients had higher disease control rates than non-overweight patients (P = 0.019, respectively). The mean progression-free survival (PFS) in overweight patients (10.23 months) was significantly longer than that of non-overweight patients (6.85 months; P = 0.027). Among patients with immune-related adverse events (irAEs), the mean PFS was also significantly longer in overweight patients (7.72 months) than in non-overweight patients (5.31 months, P = 0.034). Multivariate analysis showed that BMI was an independent prognostic factor for PFS in HCC patients treated with anti-PD-1 (hazard ratio: 0.47, P = 0.044). Thus, higher BMI predicts a better prognosis among HCC patients treated with anti-PD-1. In clinical practice, patients' BMI can provide a useful tool for predicting the efficacy of anti-PD-1 therapy.

Pembrolizumab monotherapy for untreated PD-L1-Positive non-small cell lung cancer in the elderly or those with poor performance status: A prospective observational study.

ObjectivesWe investigated the efficacy and safety of pembrolizumab monotherapy as first-line treatment for poor Eastern Cooperative Oncology Group performance status (PS) and elderly patients with programmed cell death-ligand 1 (PD-L1)-positive advanced non-small cell lung cancer (NSCLC). We also investigated clinical prognostic factors for the efficacy of pembrolizumab monotherapy, based on patient characteristics.Materials and methodsIn this prospective observational study, PS-2 and elderly NSCLC patients with PD-L1 tumor proportion score (TPS) ≥1% who received first-line pembrolizumab monotherapy, from October 2019 to March 2021, at 10 institutions in Japan were enrolled. Patients judged eligible by their physicians for combined chemotherapy and PD-1/PD-L1 inhibitors as first-line treatment were excluded. Clinicopathological characteristics and adverse events were investigated for correlation with clinical outcomes.ResultsForty patients were enrolled in the study. The median progression-free survival (PFS) of patients with PS 2 and those aged ≥ 75 years were 4.4 (95% confidence interval [CI]: 0.9–14.4) months and 5.3 (95% CI 2.9–9.4) months, respectively. The median overall survival (OS) of patients with PS 2 and those aged ≥ 75 years were 11.6 (95% CI: 1.4–not evaluable [NE]) months and 11.6 (95% CI 7.4–18.1) months, respectively. Immune-related adverse events (irAEs) were observed in 19 patients; 6 patients had severe irAEs of Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 or higher. Patients who achieved stable disease or better, had a statistically significant increase in PFS (p < 0.001) and OS (p < 0.001). In the multivariate analysis, the acquisition of disease control with pembrolizumab monotherapy was an independent prognostic factor for PFS and OS.ConclusionPembrolizumab monotherapy was relatively effective and tolerable as a first-line treatment for patients with PD-L1-positive advanced NSCLC who had poor PS or were elderly. Our results suggest that disease control might be an independent prognostic factor for PFS and OS in this population. (UMIN000044052 https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000050176)

Significance of laparoscopic cytoreductive surgery for appendiceal pseudomyxoma peritonei with limited disease and low tumor burden

ObjectiveTo investigate the clinical value of laparoscopic cytoreductive surgery (CRS) in treating of appendiceal pseudomyxoma peritonei with limited disease and low tumor burden. MethodsThe clinical data of patients with appendiceal pseudomyxoma peritonei treated by surgery with CRS at the Aerospace Center Hospital from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into laparoscopic or open CRS groups according to the operation method. A propensity score-matched (PSM) analysis (1:1) was performed, the related clinical variables were compared between the two groups, and the effect on progression-free survival (PFS) was also analyzed. ResultsOne hundred and eight patients were included in this study. After PSM, 33 patients were selected from each group and the age and peritoneal cancer index were matched between the two groups. There were significant differences in operation time (P < 0.001), intraoperative bleeding (P < 0.001), intraoperative blood transfusion (P = 0.007), hospital stay (P < 0.001). The analysis of PFS showed that there was no significant difference between the two operation methods. After multivariate analysis, the pathologic subtype (P = 0.012) was identified as an independent prognostic factor for PFS. ConclusionThe curative effect of laparoscopic CRS is like that of open operation, which can significantly shorten the operation time and hospital stay and reduce intraoperative bleeding and blood transfusion event. The laparoscopic CRS is safe and feasible in strictly selected patients. The pathologic subtype is an independent factor affecting the prognosis for PFS.

Prognostic Value of 18F-Fluorodeoxyglucose-Positron Emission Tomography/Magnetic Resonance Imaging in Patients With Hypopharyngeal Squamous Cell Carcinoma.

The aim of the study is to investigate the value of pretreatment integrated positron emission tomography/magnetic resonance imaging (PET/MRI) in predicting the prognosis of patients with hypopharyngeal squamous cell carcinoma (HSCC). Twenty-one untreated patients with HSCC who underwent PET/MRI before treatment were enrolled. We analyzed the value of PET/MRI parameters in predicting the progression-free survival (PFS) and overall survival (OS) of HSCC patients. Kaplan-Meier method and log rank test were used to perform univariate survival analysis, whereas Cox proportional hazard regression models were used to perform multivariate analysis. Of the 21 patients with a median follow-up time of 20.3 months (range, 4.2-37.6 months), 2 (9.5%) had local recurrence, 2 (9.5%) had distant metastases, and 8 (38.1%) died because of cancer. Univariate analysis showed that T stage, clinical stage, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) were significant prognostic factors for PFS (P < 0.05). T stage, clinical stage, TLG, MTV, the mean apparent diffusion coefficient (ADCmean), and the minimal apparent diffusion coefficient (ADCmin) were significant prognostic factors for OS (P < 0.05). The Cox proportional hazard regression model revealed that MTV was an independent prognostic factor for PFS, and TLG was an independent prognostic factor for OS (P < 0.05). Metabolic tumor volume was an independent predictor of PFS in patients with HSCC, while TLG was an independent predictor of OS. T stage, clinical stage, ADCmean, and ADCmin are potential prognostic indicators for HSCC. Positron emission tomography/magnetic resonance imaging can provide effective information for predicting the prognosis for HSCC patients.

852P Does sex affect the efficacy of immune checkpoint inhibitors? A national Danish melanoma study

Immune checkpoint inhibitors (ICI) are current standard in treating metastatic melanoma. In melanoma, males are known to have a poorer prognosis compared to females. However, metanalysis have shown conflicting results regarding differences in ICI efficacy between females and males. In this study, we evaluate the efficacy of ICI in a real-world Danish metastatic melanoma population according to sex. The primary endpoint was progression-free survival (PFS). Secondary endpoint was overall survival (OS) and melanoma specific survival (MSS). All patients treated with ICI (anti-PD-1 and/or anti-CTLA4) for metastatic melanoma in Denmark between 2011-2021 were identified in the Danish metastatic melanoma database. Only patients receiving ICI as first-line treatment were included. Baseline characteristics were evaluated according to ICI treatment for; age, ECOG performance status, lactate dehydrogenase (LDH), M-stage, BRAF status, the origin of melanoma (cutaneous or unknown primary melanoma), and granulocytes. Parameters for multivariate analysis were selected backwards, with a cutoff at 0.10. 1461 patients; 573 females and 888 males were identified. Baseline characteristics were significantly unbalanced between sex. A higher frequency of BRAF mutation and a lower age was found for females, however, also elevated LDH and advanced M stage. The median follow-up time for PFS was 51 months (95% CI 48-55). Multivariate analysis showed sex as a significant factor of efficacy with improved PFS for females (HR 1.16 (1.02-1.33), p=0.03). Females showed significantly better OS with a five-year survival of 46% (41%-51%) for females and 38% (34%-42%) for males. Multivariate analysis reinforced this significance with HR 1.29 (1.09-1.52). Five-year MSS rates were 49% (95% CI 44%-54%) for female and 45% (40%-49%) for male. Multivariate analysis showed significantly better MSS for females (1.20 (1.01-1.43), p=0.04). This study represents a complete, national dataset of ICI-treated metastatic melanoma patients. Baseline characteristics were unbalanced between sexes. Despite adjustments for clinical, validated prognostic factors, sex remains an independent prognostic factor for PFS, OS, and MSS in this real-world cohort.

Efficacy and Safety of Platinum Rechallenge in Patients With Platinum-resistant Ovarian, Fallopian Tube or Primary Peritoneal Cancer: A Multicenter Retrospective Study.

Ovarian cancer diagnosed with platinum-resistant recurrence has very poor prognosis and single-agent chemotherapy with no cross-resistance to prior chemotherapy is recommended for its treatment. In this study, we retrospectively evaluated the efficacy and safety of platinum rechallenge therapy for once diagnosed with platinum-resistant ovarian cancer who had a platinum-free interval (PFI) of at least 6 months. The study included 49 patients who received platinum rechallenge therapy for ovarian, fallopian tube or primary peritoneal cancer who were once diagnosed with platinum-resistant recurrence between January 2010 and March 2021 and evaluated the efficacy and safety of this treatment. In addition, patient background factors were identified, and independent prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated. A complete response was noted in 7 cases, partial response in 21, stable disease in 9, and progressive disease in 10. The response and disease control rates were 55% and 76%, respectively. The median PFS and OS were 8.5 months and 35.8 months, respectively. The independent prognostic factor was PFI for OS, and there was no independent prognostic factor for PFS. Seven patients discontinued chemotherapy owing to serious adverse events, including one patient with treatment-related death. Platinum rechallenge therapy for patients with platinum-resistant recurrence did not cause previously unreported adverse events, and the adverse events were manageable. In addition, high response and disease control rates were observed, as well as long-term OS. Platinum rechallenge therapy for platinum-resistant ovarian cancer may be a viable treatment option.

Outcomes and prognostic factors in patients with locally advanced cervical cancer treated with concurrent chemoradiotherapy

BackgroundTo investigate the prognostic factors affecting long-term survival in locally advanced cervical cancer (LACC) patients treated with concurrent chemoradiotherapy (CCRT).MethodsWe retrospectively analyzed 192 naive LACC (stage IIB–IVA) patients who underwent intensity-modulated radiotherapy (IMRT) with concurrent platinum-based chemotherapy in Xiangya Hospital from January 2014 to June 2017. The clinicopathological factors of all patients were collected. To explore the relationship between factors and prognosis, survival rates were estimated by the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards models were used to evaluate the effect of various factors on overall survival (OS) and progression-free survival (PFS). The nomogram and calibration curves were generated on the basis of survival analysis.ResultsThe median follow-up time was 39.5 months. There-year rates of OS and PFS were 89.1% and 82.8%. LACC patients with non-squamous cell carcinoma [NSCC, including adenocarcinoma or adenosquamous carcinoma (AC/ASC)], advanced stage (IIIA-IVA), initially positive lymph node (pelvic or para-aortic lymph node, PLN/PALN), and a lower pretreatment hemoglobin (HGB) level (< 126 g/L) had lower survival rates. In univariate analysis, patients with NSCC, advanced stage, PLN or PALN metastasis had worse OS. Patients with NSCC, advanced stage, PLN or PALN metastasis, and a lower pretreatment HGB level had worse PFS. In multivariate analysis, NSCC and PALN metastasis were independent prognostic parameters of OS. NSCC, PALN metastasis and a lower pretreatment HGB level were independent prognostic parameters of PFS.ConclusionsNSCC and PALN metastasis were poor prognostic factors of OS and PFS, a lower pretreatment HGB level was an independent prognostic factor of PFS in LACC patients treated with CCRT.

The prognostic significance of inflammation-immunity-nutrition score on postoperative survival and recurrence in hepatocellular carcinoma patients.

BackgroundInflammation, immunity, and nutrition status play important roles in tumorigenesis, progression, and metastasis. This study aimed to evaluate the prognostic value of Inflammation-Immunity-Nutrition Score (IINS) for overall survival (OS) and progression-free survival (PFS) in patients with hepatocellular carcinoma (HCC) undergoing radical surgery.MethodsA total of 204 HCC patients who met the criteria were included in this retrospective study: 144 in the prediction model and 60 in the validation model. IINS was constructed based on the sum of classification scores of preoperative high-sensitivity C-reactive protein (hsCRP), lymphocyte (LYM), and albumin (ALB). The associations between the IINS group and the clinicopathologic characteristics were analyzed using Pearson’s χ2 test or Fisher’s exact test. Multivariate Cox regression analysis was used to evaluate variables significant on univariate analysis. Kaplan-Meier survival curves were conducted to investigate the prognostic values of IINS, Alpha-fetoprotein (AFP) and IINS-AFP classification. The prognostic performances of all the potential prognostic factors were further compared by receiver operating characteristic (ROC) curve, and time-dependent ROC curve. The internal validation and external validation were used to ensure the credibility of this prediction model.ResultsThe patients were divided into low and high IINS groups according to the median of IINS. According to multivariate Cox regression analyses, the Barcelona Clinic Liver Cancer (BCLC) Stage (P=0.003), AFP (P=0.013), and IINS (P=0.028) were independent prognostic factors for OS, and BCLC Stage (P=0.009), microvascular invasion (P=0.030), and IINS (P=0.031) were independent prognostic factors for PFS. High IINS group were associated with significantly worse OS and PFS compared with low IINS group (P<0.001; P=0.004). In terms of clinical prognosis, IINS-AFP classification was good in group I, moderate in group II, and poor in group III. Group I had a longer OS (P<0.001) and PFS (P=0.008) compared with group II and III. ROC analysis revealed that IINS-AFP classification had a better prognostic performance for OS (AUC: 0.767) and PFS (AUC: 0.641) than other predictors, excluding its slightly lower predictive power for PFS than IINS. The time-dependent ROC curves also showed that both IINS (12-month AUC: 0.650; 24-month AUC: 0.670; 36-month AUC: 0.880) and IINS-AFP classification (12-month AUC: 0.720; 24-month AUC: 0.760; 36-month AUC: 0.970) performed well in predicting OS for HCC patients. Furthermore, the internal validation and external validation proved that IINS had good predictive performance, strong internal validity and external applicability, and could be used to establish the prediction model.ConclusionInflammation-immunity-nutrition score could be a powerful clinical prognostic indicator in HCC patients undergoing radical surgery. Furthermore, IINS-AFP classification presents better prognostic performance than IINS or AFP alone, and might serve as a practical guidance to help patients adjust treatment and follow-up strategies to improve future outcomes.

Prognostic value of systemic inflammation response index in nasopharyngeal carcinoma with negative Epstein-Barr virus DNA

BackgroundInflammatory parameters and Epstein–Barr virus (EBV) DNA status have been confirmed to be associated with prognosis in nasopharyngeal carcinoma (NPC) patients. However, there are few in-depth studies on the prognosis of NPC patients with negative EBV DNA. Our study aimed to look for inflammatory biomarkers that can identify disease progression in NPC patients with negative EBV DNA.MethodsA total of 795 NPC patients were recruited, and ultimately 325 NPC patients with negative EBV DNA were included in this study (170 in training cohort and 155 in validation cohort). Kaplan–Meier method and log-rank test were used to analyze progression-free survival (PFS) and overall survival (OS). The multivariate analysis of Cox proportional hazards regression model was used to determine the independent prognostic factors. Receiver operating characteristic (ROC) curves were used to assess prognostic value. The logistic regression was used to evaluate the relationship between EBV DNA status and inflammatory parameters. The correlation between clinical characteristics was analyzed by the chi-squared test or the Fisher’s exact test.ResultsThe optimal cutoff point for the SIRI was 1.12. The EBV DNA-negative NPC patients with high SIRI level had worse PFS and OS (all p < 0.001). In multivariate Cox proportional hazard models analysis, SIRI was an independent prognostic factor for PFS and OS (all p < 0.05), and had higher prognostic value than other indicators. Above results were found in the training cohort and confirmed in the validation cohort. In addition, EBV DNA status was not associated with any inflammatory parameters.ConclusionsThe SIRI can provide more accurate risk stratification and better prognostic prediction for NPC patients with negative EBV DNA.

Real-life analysis of treatment approaches and the role of inflammatory markers on survival in patients with advanced biliary tract cancer

Objectives Advanced stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients. Methods A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed. Results At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51–6.82), and the median overall-survival (OS) time was 16.8 months (95% CI: 13.9–19.6). Treatment choice (p < 0.001 HR:0.70 CI95% 0.55-0.9), performance status (p < 0.001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = 0.02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < 0.001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < 0.001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = 0.002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < 0.001 HR:0.55 CI 95% 0.38-0.79; p = 0.007 HR:0.51 CI95% 0.31-0.83, respectively). Conclusion SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions.

The clinical characteristics and prognostic factors of 410 patients with natural killer/T-cell lymphoma.

To investigate the clinical characteristics and prognostic factors of natural killer/T-cell lymphoma (NKTCL). We retrospectively reviewed 410 NKTCL patients admitted to our lymphoma center from 2000 to 2019. Overall survival (OS)and progression-free survival (PFS) were estimated with the Kaplan-Meier method, and the differences between the study groups were compared by the log-rank test. The median age of the 410 patients was 44(range 8-84), and the 5-year OS and PFS were 61.2% and 38.4%, respectively. For patients with stage I/II, the 5-year PFS rate was 57.5%, and the 5-year OS rate was 77.2%. For patients with stage III/IV, the 5-year PFS rate was 17.4%, and the 5-year OS rate was 43.7%. Compared to the patients who received radiotherapy alone or chemotherapy alone as their initial treatment, the patients who received combined chemoradiotherapy had longer PFS (P = 0.013). Independent prognostic factors for OS were stage III/IV (P = 0.001), elevated IPI/aaIPI score (P = 0.019), elevated PINK score (P < 0.001) and elevated plasma EBV-DNA (P = 0.003). An elevated PINK score (P < 0.001) was an independent prognostic factor for PFS. Stage III/IV, elevated IPI/aaIPI score, elevated PINK score and elevated plasma EBV-DNA were independent prognostic factors for OS. Elevated PINK score was an independent prognostic factor for PFS. In stage III/IV patients, the patients who received combined chemoradiotherapy had significantly longer PFS.

Influence of response to prior docetaxel on sensitivity to cabazitaxel in prostate cancer patients with PTEN alterations.

The purpose of this study was to investigate factors predicting the sensitivity to cabazitaxel therapy in metastatic castration‐resistant prostate cancer (mCRPC) patients with phosphatase and tensin homolog deleted from chromosome 10 (PTEN) alterations. This single‐institution, retrospective study included 12 mCRPC patients with PTEN alterations who had received cabazitaxel therapy. Five patients (41%) responded to cabazitaxel therapy with a prostate‐specific antigen (PSA) level decline of ≥30% from baseline, and all of them had responded to prior docetaxel therapy with a PSA decline of ≥30%. None of the patients with a poor response to prior docetaxel therapy responded well to cabazitaxel therapy. Of the seven patients who did not respond to cabazitaxel and whose PSA declined from baseline was <30%, five (71%) were also refractory to prior docetaxel therapy. The PSA responses to docetaxel and cabazitaxel were significantly correlated (p = 0.027). Kaplan–Meier analysis revealed that progression‐free survival (PFS) for cabazitaxel was significantly shorter for prior docetaxel nonresponders (3.3 versus 9.1 months, p = 0.028). Multivariate analysis revealed that a poor response to prior docetaxel (PSA decline < 30%) (hazard ratio [HR] = 6.382, 95% confidence interval [CI] 1.172–34.750, p = 0.032) and baseline PSA of ≥20 ng/ml (HR = 33.584, 95% CI 2.332–483.671, p = 0.010) were independent prognostic factors for PFS with cabazitaxel therapy. These results demonstrate cross‐resistance between docetaxel and cabazitaxel. The response to prior docetaxel therapy can influence the sensitivity to cabazitaxel therapy in mCRPC patients with PTEN alterations.

The diagnostic and prognostic values of circulating miRNA-1246 in multiple myeloma

ABSTRACT Background/objective Bone marrow biopsy, the gold standard for the diagnosis of multiple myeloma (MM), has main limitation of the invasiveness. Here, we explored the diagnostic and prognostic values of circulating miR-1246 in patients with MM. Material and methods Ninety MM patients and 30 healthy donors (control group) were recruited in this study. The expression of miR-1246 in the peripheral blood samples was detected using qPCR. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-1246 in MM. The Kaplan–Meier survival analyze was performed to evaluate the prognostic value of miR-1246. Results The expression level of serum miR-1246 from newly diagnosed MM patients was significantly higher than that of the control group. Circulating miR-1246 level was decreased after treatment in remission patients, but remained high levels in relapsed patients (P < 0.05). ROC analysis demonstrated that miR-1246 showed a high diagnostic value in MM with an area under the curve (AUC) of 0.952, the sensitivity of 87%, and the specificity of 95% [95% confidence interval (CI) 0.902-1.007; P < 0.001]. Kaplan–Meier analysis showed that the progression-free survival (PFS) (14.0 months vs. 26.5 months, P = 0.045) and overall survival (OS) (20.5 months vs. 55.5 months, P = 0.014) were significantly shorter in patients with high miR-1246 expression as compared with those in patients with miR-1246 low expression. Multiple Cox regression model analysis showed that circulating miR-1246 was an independent prognostic factor for PFS (HR 2.786, 95% CI: 1.420–5.467, P = 0.003) and OS (HR 2.995, 95% CI: 1.166–7.689, P = 0.023) in MM patients. Conclusion This study demonstrates that circulating miR-1246 level is elevated in MM patients, which shows high values in the diagnosis and prognosis prediction in patients with MM.

Prognostic value of the ratio of maximum to minimum diameter of primary tumor in metastatic clear cell renal cell carcinoma

BackgroundSeveral models and markers were developed and found to predict outcome of advanced renal cell carcinoma. This study aimed to evaluate the prognostic value of the ratio of maximum to minimum tumor diameter (ROD) in metastatic clear cell renal cell carcinoma (mccRCC).MethodsPatients with mccRCC (n = 213) treated with sunitinib from January 2008 to December 2018 were identified. Cutoff value for ROD was determined using receiver operating characteristic. Patients with different ROD scores were grouped and evaluated. Survival outcomes were estimated by Kaplan–Meier method.ResultsThe optimal ROD cutoff value of 1.34 was determined for progression free survival (PFS) and overall survival (OS). Patients in ROD ≥ 1.34 group had shorter PFS (9.6 versus 17.7 months, p < 0.001) and OS (25.5 versus 32.6 months, p < 0.001) than patients in ROD < 1.34 group. After adjustment for other factors, multivariate analysis showed ROD ≥ 1.34 was an independent prognostic factor for PFS (p < 0.001) and OS (p = 0.006). Patients in ROD ≥ 1.34 group presented higher proportions of pT3/4 stage (89.2% versus 10.8%, p = 0.021), WHO/ISUP grade III/IV (72.0% versus 28.0%, p = 0.010), tumor necrosis (71.0% versus 29.0%, p = 0.039), sarcomatoid differentiation (79.1% versus 20.9%, p = 0.007), poor MSKCC risk score (78.4% versus 21.6%, p < 0.001) and poor IMDC risk score (74.4% versus 25.6%, p < 0.001) than ROD < 1.34 group.ConclusionPrimary tumor with higher ROD was an independently prognostic factor for both PFS and OS in patients with mccRCC who received targeted therapy. Higher ROD was also associated with high pT stage, high WHO/ISUP grade, sarcomatoid features, tumor necrosis, poor MSKCC and IMDC risk score.

P846: EXPRESSION SIGNATURE OF TP53 BIALLELIC INACTIVATION IDENTIFIES A GROUP OF MULTIPLE MYELOMA PATIENTS WITHOUT THIS GENETIC CONDITION BUT WITH DISMAL OUTCOME.

Background: Cytogenetic abnormalities remain the most relevant prognostic factors, especially those related to TP53 gene. Biallelic inactivation of TP53, included in the definition of double-hit (DH) MM, entails an ominous prognosis, although is present in less than 5% of newly diagnosed MM (NDMM). However, ultra-high-risk MM, defined as those patients with a median survival less than 24 months, represents 15-20% of the MM population. While other high-risk cytogenetic abnormalities may account for this adverse prognosis, these kind of cytogenetic alterations are not present in all patients with such an unfavorable outcome. On the other hand, p53 can be deregulated by other mechanisms different from changes in DNA gene sequence, such as epigenetic regulation or altered expression of its regulators. Aims: To define the transcriptional signature of DH-TP53 and to find out if it was present in other patients who did not have biallelic inactivation of TP53. Methods: We analyzed RNA-seq, whole-genome and whole-exome sequencing data from 660 newly diagnosed MM (NDMM) patients from the MMRF (Multiple Myeloma Research Foundation) CoMMpass study to characterize the transcriptional signature of DH-TP53 MM. This gene signature was used to build a score based on a Spearman correlation coefficient and a scaled GINI index. Survival data were retrieved from the IA16 release and the analysis was performed using the Kaplan-Meier estimator and log-rank test. Multivariable Cox models were fitted in R. GSE4581 and GSE136400 gene expression series from GEO were used as validation cohorts. Results:TP53 biallelic inactivation, defined in this work as DH-TP53 group, was found in 23 out of 660 patients (3.5%) and was associated with an exclusive gene expression signature consisted of 78 genes. Based on these genes, we calculated the DH-TP53 score, which identified a subgroup of 50 patients that shared the same transcriptional profile (DH-TP53-like group). The prognosis of this group was particularly unfavorable with a median overall survival (OS) of 23 months; and a progression-free survival (PFS) of 15 months, even worse than that described for DH-TP53 patients (HR = 1.83 [95% CI, 1.00-3.35], p = 0.046). The prognostic value of the DH-TP53 was confirmed as an independent prognostic factor for PFS (HR 3.84 [95% CI 2.51-5.88], p < 0.001) and OS (HR 3.32 [95% CI, 2.31-4.77], p < 0.001) in the multivariable analysis. We also observed that survival for any of the cytogenetic abnormalities was significantly shortened in the DH-TP53-like group (p < 0.05). Furthermore, the prognostic value of the DH-TP53 score was externally validated using gene expression data obtained by microarray analysis Image:Summary/Conclusion: The expression signature of DH-TP53 MM was shared by other MM patients without TP53 biallelic inactivation (DH-TP53-like group). The DH-TP53 score identified an ultra-high-risk group of MM patients with a median overall survival below 24 months. In addition, this score refined the prognostic stratification of cytogenetic abnormalities, and was externally validated using expression data analyzed by microarrays. Funding: This study has been funded by ISCIII (PI16/01074 and PI19/00674) (co-funded by FEDER), Castilla y Leon (GRS 2058/A/19 and GRS 2331/A/21) and AECC (PROYE20047GUTI). CDR, EAR and IJCB were supported by the AECC (CLJUN18010DERA), the “Consejería de Educación de Castilla y León” and the ISCIII (FI20/00226), respectively.

S148: VENETOCLAX-OBINUTUZUMAB FOR PREVIOUSLY UNTREATED CHRONIC LYMPHOCYTIC LEUKEMIA: 5-YEAR RESULTS OF THE RANDOMIZED CLL14 STUDY

Background: One-year fixed-duration venetoclax-obinutuzumab (Ven-Obi) has demonstrated significant improvement of progression-free survival (PFS) as compared to chlorambucil-obinutuzumab (Clb-Obi) in patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions in the CLL14 trial. As high rates of undetectable minimal residual disease (uMRD) suggested deep remissions, long-term efficacy data including patients with high-risk disease is of particular interest. Aims: The aim of this report is to provide updated efficacy and safety data from the ongoing follow-up of the CLL14 study with all patients being off study treatment for ≥ 4 years. Methods: Patients with previously untreated CLL and coexisting conditions were randomized 1:1 to 12 cycles of venetoclax with 6 cycles of obinutuzumab or 12 cycles of chlorambucil with 6 cycles of obinutuzumab. The primary endpoint was investigator-assessed PFS. Secondary endpoints included safety, rates of MRD response (measured every 3-6 months up to 9 years after last patient enrolment), time to next treatment (TTNT) and overall survival. Follow-up is ongoing, all patients are off study treatment. Results: Of the 432 enrolled patients, 216 were randomly assigned to receive Ven-Obi and 216 to receive Clb-Obi. With a current median follow-up of 65.4 months (interquartile range 52.6-69.4), PFS remained significantly superior for Ven-Obi compared to Clb-Obi (median not reached [nr] vs 36.4 months; hazard ratio [HR] 0.35 [95% CI 0.26-0.46], p<0.0001). At 5 years after randomization, the estimated PFS rate was 62.6% after Ven-Obi and 27.0% after Clb-Obi. Overall, 52 cases of progressive disease (PD) with 28 required second-line treatments occurred in the Ven-Obi arm and 132 with 86 second-line treatments in the Clb-Obi arm. TTNT was significantly longer after Ven-Obi (5-year TTNT 72.1% vs 42.8%; HR 0.42, 95% CI 0.31-0.57, p<0.0001). In both arms, the majority of next-line therapies were BTK inhibitors (54.3% in the Ven-Obi arm, 47.1% in the Clb-Obi arm). The PFS and TTNT difference was maintained across all risk groups, including patients with TP53 mutation/deletion (5-year PFS 40.6% vs 15.6%; 5-year TTNT 48.0% vs 20.8%) and unmutated IGHV status (5-year PFS 55.8% vs 12.5%; 5-year TTNT 66.2% vs 25.1%). A multivariable analysis indicated 17p deletion and high disease burden as independent prognostic factors for PFS in patients treated with Ven-Obi. Four years after treatment completion, 39 (18.1% of the intention-to-treat population) patients in the Ven-Obi arm still had uMRD (<10-4 by NGS in peripheral blood), 27 (12.5%) had low (L)-MRD (≥ 10-4 and < 10-2) and 41 (19.0%) high (H)-MRD (≥ 10-2), compared to 4 (1.9%) uMRD, 13 (6.0%) L-MRD and 24 (11.1%) H-MRD in the Clb-Obi arm. Overall, 40 deaths were reported in the Ven-Obi arm (8 PD related) and 57 in the Clb-Obi arm (23 PD related); at 5 years after randomization the estimated OS rate was 81.9% in the Ven-Obi arm and 77.0% in the Clb-Obi arm (HR 0.72 [0.48-1.09], p=0.12). Second primary malignancies were reported in 44 (20.8%) patients in the Ven-Obi arm and 32 (15.0%) in the Clb-Obi arm. No new safety signals were observed. Image:Summary/Conclusion: These data confirm that over 60% of patients who had received 1-year fixed-duration Ven-Obi have remained in remission four years after end of therapy. The majority of patients treated with Ven-Obi still have not required a second line of CLL therapy. Hence, the 1-year Ven-Obi regimen continues to be an effective fixed-duration option for patients with CLL and coexisting conditions, also in the context of high-risk disease.

The Prognostic Value of Gastric Immune Prognostic Index in Gastric Cancer Patients Treated With PD-1/PD-L1 Inhibitors.

Objective: This study aimed to investigate the prognostic value of the gastric immune prognostic index (GIPI) in gastric cancer patients treated with programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. Methods: This study was conducted to elucidate the role of GIPI using the data from 146 gastric cancer patients treated with PD-1/PD-L1 inhibitors between August 2016 and December 2020 in Harbin Medical University Cancer Hospital. The GIPI calculation was based on dNLR and LDH. Patients were categorized into three groups: 1) GIPI good (LDH ≤250 U/L and dNLR ≤3); 2) GIPI intermediate (LDH >250 U/L and NLR >3); 3) GIPI poor (LDH >250 U/L and dNLR >3). The correlations between GIPI and clinicopathologic characteristics were determined by the Chi-square test or the Fisher’s exact test. The Kaplan–Meier analysis and log-rank test were used to calculate and compare progression-free survival (PFS) and overall survival (OS). The univariate and multivariate Cox proportional hazards regression model was used to detect prognostic and predictive factors of PFS and OS. Results: 146 patients treated with PD-1/PD-L1 inhibitors were included in this study, of which, 72.6% were GIPI good, 23.3% were GIPI intermediate, and 4.1% were GIPI poor. The GIPI was associated with the common blood parameters, including neutrophils and lymphocytes. The multivariate analysis showed that platelet, TNM stage, and treatment were the independent prognostic factors for PFS and OS. Patients with GIPI intermediate/poor were associated with shorter PFS (median: 24.63 vs. 32.50 months; p = 0.078) and OS (median: 28.37 months vs. not reached; p = 0.033) than those with GIPI good. GIPI intermediate/poor was correlated with shorter PFS and OS than GIPI good, especially in subgroups of patients with ICI treatment and patients with PD-1/PD-L1 positive status. Conclusions: The GIPI correlated with poor outcomes for PD-1/PD-L1 expression status and may be useful for identifying gastric cancer patients who are unlikely to benefit from treatment.

A predictive model based on liquid biopsy for non-small cell lung cancer to assess patient’s prognosis: Development and application

Background and objectiveImproving ability to predict the prognosis of patients with progressive lung cancer is an important task in the era of precision medicine. Here, a predictive model based on liquid biopsy for non-small cell lung cancer (NSCLC) was established to improve prognosis prediction in patients with progressive NSCLC. MethodsClinical data and blood samples of 500 eligible patients were collected and screened from the electronic case database and blood sample center of Hwa Mei Hospital, University of Chinese Academy of Sciences and Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences. Patients were randomly assigned to training set (300 cases) and validation set (200 cases) in a ratio of 3:2 by random number method. Baseline levels of the two datasets were compared. Progression-free survival (PFS) analysis was performed on the training set using Kaplan-Meier method. The independent prognostic factors affecting patients’ PFS were determined by multivariate Cox regression analysis. The prognosis predictive model of patients was constructed by using the nomogram. Calibration curve and C-index were used to evaluate the accuracy of the prognosis predictive model in both internal and external validations. ResultsIn training set, the age distribution of patients was 59.00 (46.00, 71.00) years, including 137 (45.7 %) females and 163 (54.3 %) males, 198 cases (66.0 %) with Eastern Cooperative Oncology Group (ECOG) score 0–1, and 102 cases (34.0 %) with ECOG score 2. In verification set, the age distribution of patients was 60.00 (48.25, 73.00) years, including 92 females (46.0 %) and 108 males (54.0 %), 130 cases (65.0%) with ECOG score 0–1, and 70 cases (35.0 %) with ECOG score 2. Patients in training set showed PFS differences stratified by gene mutation type (p < 0.0001), differentiation degree (p < 0.0001), circulating tumor cell (CTC) content (p = 0.00026), and brain metastasis (p < 0.0001). Besides, multivariate Cox regression analysis indicated that gene mutation type, differentiation degree, CTC content (p = 0.002), and brain metastasis (p = 0.005) are independent prognostic factors for PFS. These factors were included in the nomogram parameters, and both internally validated calibration curve (C-index = 0.672) and externally validated calibration curve (C-index = 0.657), showing good predictive performance of the model. ConclusionThe predictive model has a good predictive ability for prognosis of patients with progressive NSCLC. Notably, the differentiation degree and CTC content are both impact factors for PFS of patients, and the performance of these indicators in predicting the survival of patients with progressive NSCLC needs to be clarified in the future.