Post-progression Survival In Patients Research Articles

Post-Progression Survival in Patients with Oligometastatic or Polymetastatic Pancreatic Adenocarcinoma

Distant progression following surgical resection of stage I-III pancreatic ducal adenocarcinoma (PDAC) is a major cause of morbidity and mortality. Herein, we investigated the impact of tumor burden at the time of distant progression on survival. We hypothesize that patients with limited number of metastases (≤5) in a single organ will have improved survival post progression. We queried our institutional database for patients with the following inclusion criteria: 1-Stage I-III PDAC who underwent curative resection, and 2-Metachronous single organ (liver or lung) distant failure >3 months from the date of surgery. Patients with serosal and/or multiple organ metastases were excluded. Single organ metastases other than liver or lung were also excluded. Patients were stratified into oligometastatic (≤5 tumors), and polymetastatic (>5 tumors). Primary endpoint was survival post failure, while secondary endpoints were distant failure free survival (DFFS) and overall survival. Reverse KM curve was used to calculate median follow up. KM curves were plotted for DFFS identified from date of surgery until date of distant failure, survival post failure was identified from date of distant failure until death/last follow up, and overall survival was identified from date of surgical resection until death/last follow up. Out of 128 patients who developed metachronous distant progression following surgical resection, we identified 76 patients who met the inclusion criteria with a median follow up of 50 months. Among those, at the time of distant failure, 63% (n = 48) and 37% (n = 28) patients had ≤5 vs >5 metastases respectively. Median number of metastases was one (range 1-5) and eight (range 6-33), while 12 and 11 patients developed local failure in the oligometastatic and polymetastatic cohorts respectively. Among the 48 patients who developed oligometastases, 69% (n = 33) and 31% (n = 15) had liver and lung metastases respectively. On the other hand, 68% (n = 19) and 32% (n = 9) had liver and lung polymetastases respectively. Median DFFS was 11, and 9 months (HR = 1.59, 95 % CI 0.95-2.64, p value = 0.046), survival post distant failure was 17.8 and 5.3 months (HR = 3.03, 95 % CI 1.52-6.01, p value<0.0001), and median survival was 29.8, and 16.7 months (HR = 2.52, 95 % CI 1.31-4.86, p value = 0.0007) among patients with oligometastases and polymetastases respectively. Within the surgically resected stage I-III PDAC who developed single organ liver or lung metachronous disease, oligometastases (one-five lesions) were more prevalent, had more durable DFFS, had improved survival post failure, and a longer median survival compared to patients with polymetastatic recurrence (>five metastases). Trials on treatment of metastatic PDAC should stratify by number of metastases, and the oligometastatic subset may derive survival benefit from ablative radiation therapy.

Analysis of the effect of clinical and laboratory parameters on survival in patients with metastatic renal cell cancer with intermediate prognosis according to IMDC (International mRCC Database Consortium)

Introduction. Most patients with metastatic renal cell carcinoma (mRCC) who received systemic therapy are classified into as intermediate risk group according to the International mRCC Database Consortium (IMDC) assessment. However, survival differs in patients with one and two unfavourable prognostic risk factors.Objective. To analyze the impact of possible clinical and laboratory parameters on survival in mRCC patients with intermediate prognosis according to IMDC in the presence of one or two unfavourable prognostic risk factors.Materials &amp; methods. A retrospective analysis of data from 316 mRCC patients with intermediate prognosis receiving systemic therapy was carried out. The presence and effect on survival of the following laboratory parameters were compared: hemoglobin, neutrophil count, LDH, platelet count, alkaline phosphatase, serum calcium level, ESR, and emphasis was also placed on the time of metastases appearance. Overall survival (OS), post-progression survival (PPS), and 3- and 5-year survival were evaluated.Results. The overall 3- and 5-year survival rate for subgroups with one and two unfavourable prognostic risk factors were 85.2% ± 1.8% and 58.1 ± 1.6%; 79.1% ± 1.7% and 35.6  1.6%, respectively (p &lt; 0.001). Three- and 5-year PPS for both subgroups amounted to 66.1% ± 1.6% and 21.8% ± 1.4%; 45.2% ± 1.5% and 12.2% ± 1.3%, respectively (p &lt; 0.001). Median for OS was 61 and 51 months and PPS was 50 and 32 months respectively (p &lt;0.001). No statistically significant difference was found in the frequency of gradations of the investigated laboratory indicators with a predictive effect on prognosis, depending on the number of a unfavourable prognostic risk factors. There were also no significant differences in survival rates when laboratory parameters deviated from the normal, except for hemoglobin: OS in patients with one prognostic factor is significantly higher with normal hemoglobin (p &lt; 0.05). In the future, considering the absence of influence of the selected factors on survival rates with their obvious significant differences in patients with one and two prognostic factors, the influence of the time of appearance of metastases (synchronous / metachronous) was analysed: all survival parameters were significantly worse in patients with synchronous metastases. Furthermore, OS in patients with metachronous metastases with the same relapse-free period was significantly better in patients with one prognostic factor according to IMDC.Conclusions. The presence of one or two prognostic factors significantly affects the indicators of 3 and 5-year overall survival and PPS in patients with an intermediate prognosis of mRCC, while laboratory parameters do not affect survival, except for hemoglobin levels, the time of metastases appearance has a significant effect, and the time of metastases appearance has a significant effect.

RNF220 promotes gastric cancer growth and stemness via modulating the USP22/wnt/β-catenin pathway

Gastric cancer (GC) is a prevalent malignancy that seriously threatens the health and life of patients. Although Ring finger 220 (RNF220) has been demonstrated to participate in the development of various cancers, its role and mechanism in GC remain undiscovered. The expression of RNF220 was determined by The Cancer Genome Atlas (TCGA) database and Western blot. Additionally, the overall survival (OS) and post-progression survival (PPS) were analyzed based on the levels of RNF220 in the TCGA database. The role and mechanism of RNF220 in growth and stemness were investigated using cell counting kit-8, colony formation, sphere-formation, co-immunoprecipitation, and Western blot experiments. Furthermore, the role of RNF220 was investigated in a xenografted mouse model. The expression of RNF220 was found to be upregulated in GC, which predicted unfavorable OS and PPS in patients with GC. Knockdown of RNF220 reduced cell viability, colony numbers, numbers of spheres formation, and the relative protein levels of Nanog, Sox2, and Oct4 in both AGS and MKN-45 cells. Moreover, overexpression of RNF220 increased cell viability and the numbers of spheres formation in MKN-45 cells. Mechanistically, RNF220 bound to USP22, and interference of RNF220 downregulated the Wnt/β-catenin axis via USP22, which was confirmed by the overexpression of USP22 in both cell lines. Furthermore, silencing of RNF220 significantly decreased tumor volume and weight, the level of Ki-67, and the relative protein levels of USP22, β-catenin, c-myc, Nanog, Sox2, and Oct4. Taken together, downregulation of RNF220 suppressed GC cell growth and stemness by downregulating the USP22/Wnt/β-catenin axis.

Prognostic significance of SPARC expression in non-small cell lung cancer: A meta-analysis and bioinformatics analysis.

The aim of the present study was to elucidate the significance of secreted protein acidic and cysteine rich (SPARC) expression in non-small cell lung cancer (NSCLC) in terms of clinicopathology, immune-cell infiltration and survival prognosis. A meta-analysis and bioinformatics analysis were performed using studies retrieved with PubMed, Web of Science, Wanfang Data and the Chinese National Knowledge Infrastructure databases. The meta-analysis suggested that, compared with normal tissues, SPARC expression was elevated in NSCLC tissues. The expression of SPARC was not significantly associated with TNM stage and lymph-node metastasis, and was positively associated with patient gender. Regarding the differential expression of SPARC and the relationship between expression levels and survival, the Oncomine database was consulted and Kaplan-Meier curves were drawn. It was indicated that SPARC mRNA expression levels were higher in NSCLC tissues than in normal tissues. Low expression of SPARC mRNA was negatively associated with overall survival, first progression survival and post-progression survival of patients. Further exploration of the relationship between SPARC expression and survival by univariate analysis indicated that TNM stage, lymph node metastasis, distant metastasis and depth of infiltration of lung cancer were negatively associated with patient prognosis. Cox multifactorial analysis suggested that SPARC expression levels and TNM stage were risk factors significantly affecting the prognosis of patients with NSCLC. Analysis with the GEPIA and UALCAN databases further indicated that the mRNA expression level of SPARC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) was higher than that in normal lung tissue, and the SPARC expression levels were affected by factors such as the TNM stage of lung cancer. A lower the level of SPARC mRNA expression was associated with a better relative survival prognosis of patients. In the Human Protein Atlas database, the expression level of SPARC protein was higher in LUAD and LUSC than in normal lung tissue. In the Timer database, the expression level of SPARC was closely linked to immune cells related to the occurrence of lung cancer, and the degree of immune-cell infiltration and SPARC protein expression were closely related to the prognosis of patients with lung cancer. Immune cells were indicated to exhibit significant inhibition of DNA proliferation mutation mechanisms in lung cancer (P<0.05). In summary, SPARC expression may be used as a valuable indicator of prognosis in patients with NSCLC, which may provide new approaches for preventative treatment.

Progression Patterns and Post-Progression Survival in Recurred Intrahepatic Cholangiocarcinoma Patients: A Novel Prognostic Nomogram Based on Multicenter Cohorts.

BackgroundThe post-progression survival (PPS) of recurred intrahepatic cholangiocarcinoma (iCCA) patients relates to the characteristics of tumor progression. Moreover, the prediction model of PPS in those patients has not been well established. This study aimed at developing a novel nomogram for predicting PPS in recurred iCCA patients.MethodClinical characteristics were retrospectively collected in 396 patients diagnosed with iCCA from cohorts of Sun Yat-sen University Cancer Center (SYSUCC) and the First Hospital of Dalian Medical University (FHDMU). The PPS in patients with different progression patterns was investigated. The nomogram of PPS was established with the Cox regression model in the primary cohort. Then the nomogram was verified in the external validation cohort.ResultsLiver progression was the commonest pattern (42.08%) in recurred iCCA patients, while patients with local LN progression had significantly better PPS than those with other patterns. The independent prognostic factors comprised elevated CEA levels, tumor differentiation, N stage 8th, adjuvant therapy, Local LN metastasis, Liver Metastasis only, and Multiple Metastasis. The nomogram constructed on these factors achieved satisfied C-indexes of 0.794 (95% CI 0.769–0.828) and 0.827 (0.779–0.876) for the training and validation cohorts, respectively. These values were significantly higher than those of the 8th TNM stage system (all p < 0.001). The recurred iCCA patients could be precisely classified into high- and low-risk groups according to the cutoff point of this nomogram (p < 0.01).ConclusionThe investigation of progression patterns and the development of this nomogram can offer new evidence to precisely postoperative and post-progression management of iCCA patients.

Clinical impact of post-progression survival in patients with locally advanced non-small cell lung cancer after chemoradiotherapy.

BackgroundThe efficacy of first-line chemoradiotherapy for overall survival (OS) might be confounded by the subsequent treatments in patients with locally advanced non-small cell lung cancer (NSCLC). In this study, we assessed the associations of progression-free survival (PFS) and post-progression survival (PPS) with OS after chemoradiotherapy for locally advanced NSCLC using patient-level data.Patients and methodsBetween January 2011 and December 2018, 45 patients with locally advanced NSCLC who had received first-line chemoradiotherapy and in whom recurrence occurred were analysed. The associations of PFS and PPS with OS were analysed at the individual level.ResultsLinear regression and Spearman rank correlation analyses revealed that PPS was strongly correlated with OS (r = 0.72, p < 0.05, R2 = 0.54), whereas PFS was moderately correlated with OS (r = 0.58, p < 0.05, R2 = 0.34). The Glasgow prognostic score and liver metastases at recurrence were significantly associated with PPS (p < 0.001).ConclusionsThe current analysis of individual-level data of patients treated with first-line chemoradiotherapy implied that PPS had a higher impact on OS than PFS in patients with locally advanced NSCLC. Additionally, current perceptions indicate that treatment beyond progression after first-line chemoradiotherapy might strongly affect OS.

Cabozantinib beyond progression improves survival in advanced renal cell carcinoma patients: the CABEYOND study (Meet-URO 21)

ABSTRACT Background Cabozantinib improves survival in metastatic renal cell carcinoma (mRCC) after prior antiangiogenics. The best treatment at disease progression (PD) is unknown. Being also a AXL/MET inhibitor, involved in acquired resistance, we hypothesized a prolonged tumor growth control in patients continuing cabozantinib despite PD. Research Design and Methods This retrospective multicenter study enrolled patients receiving cabozantinib after the first line between 2014 and 2020. We compared patients maintaining cabozantinib after first PD due to clinical benefit and good tolerability with those who changed therapy. The postprogression survival (PPS) of both was our primary endpoint. Results We analyzed 89 patients: 45 received cabozantinib beyond PD and 44 switched therapy. 40.4%, 31.5%, and 28.1% of patients received 1, 2, or >2 prior treatment, respectively. 84.3% were intermediate-poor International Metastatic Renal Cell Carcinoma Database risk. Patients continuing cabozantinib showed a higher response rate to cabozantinib before PD (46.7% vs 25%, p = 0.03) and were more heavily pretreated. Continuing cabozantinib showed a significantly longer PPS compared with switching therapy (median PPS 16.9 vs 13.2 months, HR 0.66, 95%CI 0.48–0.92, p = 0.011). Conclusions We observed longer PPS in patients continuing cabozantinib beyond PD, suggesting that this could be an effective option.

Prognostic significance of KIF23 expression in gastric cancer.

BACKGROUNDKinesin super family 23 (KIF23) is a member of the KIF family, and it plays an important role in mitosis and cytokinesis. Loss of expression can cause mitotic arrest. The Oncomine database is one of the largest oncogene chip databases in the world, and is an integrated data mining platform for cancer gene information. By querying the database, differences in expression between tumor tissue and normal tissue can be determined.AIMTo study the expression and prognostic significance of KIF23 in gastric cancer (GC).METHODSWe used immunohistochemistry to compare the expression of KIF23 in GC and normal gastric tissues. We mined the data on the expression and prognosis of KIF23 in GC using Oncomine and Kaplan–Meier plotter database.RESULTSCompared with normal gastric tissues, KIF23 expression was increased in GC tissues, and correlated with T, N, and tumor–node–metastasis stages. Survival analysis showed that patients with high expression of KIF23 had a poor overall survival. There were five studies in the Oncomine database in which expression of KIF23 was significantly higher in GC tissues than in normal gastric tissues (P < 0.05). Kaplan–Meier plotter database analysis showed that recurrence-free survival, overall survival, distant metastasis free survival, and post progression survival of patients with high expression of KIF23 were lower than those of patients with low expression. Further stratified analysis found that prognostic survival indicators worsened in patients with T2 and T3 poorly differentiated adenocarcinoma with high expression of KIF23.CONCLUSIONKIF23 is highly expressed in GC and is associated with a poor prognosis of patients. It may be of great significance in the diagnosis, treatment, and prognostic evaluation of GC.

Analysis of Post-Progression Survival in Patients with Unresectable Hepatocellular Carcinoma Treated with Lenvatinib

Background: Although a strong antitumor effect of lenvatinib (LEN) has been noted for patients with unresectable hepatocellular carcinoma (HCC), there are still no reports on the prognosis for patients with disease progression after first-line LEN therapy. Methods: Patients (n = 141) with unresectable HCC, Child-Pugh class A liver function, and an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 who were treated with LEN from March 2018 to December 2019 were enrolled. Results: One hundred and five patients were treated with LEN as first-line therapy, 53 of whom had progressive disease (PD) at the radiological evaluation. Among the 53 patients with PD, there were 27 candidates for second-line therapy, who had Child-Pugh class A liver function and an ECOG-PS of 0 or 1 at progression. After progression on first-line LEN, 28 patients were treated with a molecular targeted agent (MTA) as second-line therapy (sorafenib: n = 26; ramucirumab: n = 2). Multivariate analysis identified modified albumin-bilirubin grade 1 or 2a at LEN initiation (odds ratio 5.18, 95% confidence interval [CI] 1.465–18.31, p = 0.011) as a significant and independent factor for candidates. The median post-progression survival after PD on first-line LEN was 8.3 months. Cox hazard multivariate analysis showed that a low alpha-fetoprotein level (<400 ng/mL; hazard ratio [HR] 0.297, 95% CI 0.099–0.886, p = 0.003), a relative tumor volume <50% at the time of progression (HR 0.204, 95% CI 0.07–0.592, p = 0.03), and switching to MTAs as second-line treatment after LEN (HR 0.299, 95% CI 0.12–0.746, p = 0.01) were significant prognostic factors. Conclusion: Among patients with PD on first-line LEN, good liver function at introduction of LEN was an important and favorable factor related to eligibility for second-line therapy. In addition, post-progression treatment with MTAs could improve the prognosis for patients who had been treated with first-line LEN.

Estimated clinical efficacy and radiographic response characteristics of PD1 inhibition in newly diagnosed and recurrent glioblastoma in clinical practice: A report from the iRANO Working Group.

2521 Background: Despite concerns of immunotherapy-induced inflammatory response during PD1 inhibition, questions remain as to the true incidence of inflammatory response and potential clinical implications. The goals of the project were to use GBM patients pooled from academic centers to estimate radiographic PFS and OS, as well as determine the incidence of immunotherapy-induced inflammatory response. Methods: 152 patients with newly diagnosed (N = 57) or recurrent (N = 95) GBM treated with either nivolumab or pembrolizumab from Dana-Farber (N = 88), UCLA (N = 35) or UCSF (N = 29) were included in this study. Radiographic progression was defined by a 25% increase in bidirectional measurements according to RANO. Results: Median PFS and OS for newly diagnosed patients was 162 and 520 days, respectively, while median PFS and OS for recurrent patients was 72 and 225 days, respectively. No difference in OS was observed in recurrent patients treated with nivolumab vs. pembrolizumab (P = 0.58), but recurrent patients treated with nivolumab trended toward a longer PFS (P = 0.097). Of the recurrent patients with OS and PFS data available and radiographic progression, 95% of them progressed within 6 mos of starting treatment. Median post-progression survival (PPS) in recurrent patients with PFS &lt; 6 mos was 151 days, while PPS for patients with PFS &gt; 6 mos was 178 days (P = 0.51). In the 77 recurrent patients who progressed within 6 mos, 36.4% had an OS that was &gt; 9 mos, while 63.6% had an OS &lt; 9 mos, suggesting the majority of patients with “early progression” also died early and a minority of patients had what could be considered “immune-related inflammation”. Of the 81 recurrent patients with documented progression, only 2.5% showed stabilization within 3 mos of first progression, 30.9% died before the 3-month confirmation scan could be obtained, 24.7% showed continued tumor growth by 3 months, and 48.1% had no follow-up confirmatory imaging exams. Of the 70 patients who progressed within 6 mos and had documented death, 2.9% had disease stabilization, 31.4% died before the 3-month confirmation, and 75.7% had either documented tumor growth or had no follow-up confirmatory imaging exams. Conclusions: This study suggests immunotherapy-induced inflammation followed by a favorable PPS is uncommon in GBM. While patients treated with other types of immunotherapy may exhibit different imaging characteristics, these data provide an important basis to refine the iRANO criteria.

The Pattern of Progression Defines Post-progression Survival in Patients with Hepatocellular Carcinoma Treated with SIRT.

In patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, post-progression survival (PPS) is marked by the pattern of progression. Our aim was to assess the influence of the pattern of progression to selective internal radiotherapy (SIRT) in PPS among patients with HCC. A retrospective analysis of patients treated with SIRT between 2003 and 2015 was conducted, excluding those with a single nodule < 5cm or with metastases. Four patterns of progression to SIRT were defined: target tumour growth, non-target tumour growth, new intrahepatic disease, and new extrahepatic disease. PPS was calculated from the time of progression based on RECIST 1.1 criteria. Out of the 102 patients who met the selection criteria, 76 progressed after a median follow-up of 15months. Median PPS was 6.5months (95% CI 3.8-9.3months). Patients who progressed at pre-existing lesions had a better PPS (median 12.5months) than those who progressed with new lesions inside or outside the liver (median 4.2months) (p = 0.02). In a Cox model adjusted by liver function and systemic inflammation, the pattern of progression had a hazard ratio of 1.64 (95% CI 0.92-2.93; p = 0.093). In a cohort of HCC patients treated with SIRT, the pattern of progression associated with worst survival was the development of new intrahepatic lesions or extrahepatic metastases.

CDK1 serves as a potential prognostic biomarker and target for lung cancer.

ObjectiveEvidence from cell and mouse models and human tissues suggests that cyclin dependent kinase 1 (CDK1) is involved in lung cancer (LC) tumorigenesis. However, the different types of expression patterns and prognostic results of CDK1 need further analysis.MethodsIn the current study, we assessed CDK1 expression and LC patient outcomes using data from the Oncomine, GEPIA, and Kaplan–Meier Plotter databases. Additionally, mutations in the CDK1 gene were analyzed by using the cBioPortal database. The expression of CDK1 was verified by real-time quantitative PCR using the Human Protein Atlas database and human tissues.ResultsExpression of CDK1 was higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in normal lung samples. Moreover, CDK1 expression was linked to disease progression. Survival analysis indicated that upregulation of CDK1 was related to poor overall survival, low first progression, and post-progression survival in patients with LC.ConclusionsOur results indicate that CDK1 is a potential clinical target and prognostic biomarker for patients with LC.

The prognosis of patients with recurrent or persistent ovarian clear cell carcinoma: Results from a randomized phase III study (JGOG3017/GCIG).

5515 Background: There are currently no concise data on prognosis in patients with recurrent or persistent clear cell carcinoma (CCC). The JGOG3017/GCIG was a randomized phase III trial to compare paclitaxel plus carboplatin (TC) to CPT-11 plus cisplatin (CPT-P) for stage I to IV CCC patients who have been diagnosed by central pathological review (CPR). A total of 619 patients were eligible for efficacy analyses. The aim of this study was to investigate prognosis of these patients with recurrent or persistent CCC. Methods: We estimated median and restricted mean survival time (RMST) of post-progression survival (PPS) of patients with recurrent or persistent CCC by platinum sensitivity, treatment arm, crossover chemotherapy, primary stage, residual tumor, performance status and ethnicity. PPS rates at 6, 12, 18 and 24-month were also calculated. Results: Among the 619 patients, the recurrence rate of stages was as follows: 6.3% (6/96) in stage IA/IB, 14.6% (46/315) in stage IC, and 54.8% (114/208) in stage II- Ⅳ. The recurrence rate of surgical situations was as follows: 19.4% (106/544) in complete surgery, 75% (27/36) in optimal, and 84.6% (33/39) in suboptimal. Overall, 166 of 619 patients had recurrent disease. The median PPS were 14.0 months (95% confidence interval [CI], 12.6 – 17.9) for all patients, 13.5 months (95% CI, 11.4 – 19.6) in the TC group (n=77) and 14.4 months (95% CI, 11.0 - 18.8) in the CPT-T group (n=89), with no significant difference between the two groups (hazard ratio, 1.02; 95% CI, 0.71 - 1.47, log-rank P = 0.898). The RMST of PPS for all patients was 14.6 months (95% CI, 13.3 - 15.8). Median PPS for patients with platinum-resistant (44.6%, n=74) and platinum-sensitive (53.0%, n=88) disease were 10.9 months (95% CI, 8.9 - 13.3) and 18.8 months (95% CI, 15.0 - 28.7) (HR, 1.88; 95% CI, 1.30-2.72, p&lt;0.001), respectively. Conclusions: The median PPS of patients with platinum-resistant recurrence was significantly shorter than that of patients with platinum-sensitive recurrence. Data on PPS in patients with recurrent CCC that will be the basis of a future clinical trial in such patients were obtained.

Post-progression survival after cessation of treatment with nivolumab for advanced non-small cell lung cancer: A retrospective study.

ObjectivesThe effectiveness of treatment after cessation of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) has not been well investigated. The aim of the present study was to clarify the clinical benefit of post-nivolumab treatment in such patients.Materials and methodsA retrospective review was conducted on patients who received treatment after cessation of nivolumab due to disease progression or adverse events at the Toneyama National Hospital between January 2016 and April 2017.ResultsAmong 64 patients treated with nivolumab, 26 patients received treatment after cessation of nivolumab due to disease progression (n = 21) or adverse events (n = 5). The median age of the patients was 68 years and 19 patients were male. Nineteen patients had performance status (PS) 1 or less at initiation of post-nivolumab treatment. Four, 20, and 2 patients were treated with platinum doublets, a single agent, and molecular targeting agents, respectively. Response rate, disease control rate, and median progression-free survival of first-line post-nivolumab treatment were 34.6% (9 patients), 73.1% (19 patients), and 2.8 months (95% confidence interval [CI]: 1.7–5.2), respectively. Adverse events (≥ grade 3) and treatment cessation were observed in 57.7% (15 patients) and 19.2% (5 patients), respectively. There were no statistically significant differences for the majority of patient characteristics between the groups with (n = 26) and without post-nivolumab treatment. However, PS at cessation of nivolumab and post-progression survival (PPS) after cessation of nivolumab (median PPS: 12.6 vs. 1.4 months, 95% CI: 3.8–14.7 vs. 0.4–2.2) were significantly different between the groups. A multivariate Cox regression analysis showed significant correlation of PS at cessation of nivolumab (hazard ratio [HR]: 0.34, 95% CI: 0.13–0.87) and post-nivolumab treatment (HR: 0.19, 95% CI: 0.08–0.43) with prolonged PPS after nivolumab.ConclusionMedian post-progression survival in patients with advanced NSCLC who received post-nivolumab treatment was approximately 1 year.

Prognostic Factors Associated with Postprogression Survival in Advanced Hepatocellular Carcinoma Patients Treated with Sorafenib Not Eligible for Second-Line Regorafenib Treatment

Objectives: The aim of this study was to investigate the prognostic factors associated with postprogression survival (PPS) in advanced hepatocellular carcinoma (HCC) patients treated with sorafenib, who were not eligible for second-line treatment with regorafenib. Methods: A total of 103 patients with radiological confirmation of progressive disease (PD) were enrolled. Results: The median PPS (n = 67) was 6.1 months. Significant and independent prognostic factors at initial radiological PD associated with good PPS were an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0, the absence of macrovascular invasion (MVI), and time to progression (TTP) ≥4 months. Upon scoring these three variables as good PPS factors, the median PPS in the good PPS score of 3 or 2 group (n = 38) was significantly longer than that in the good PPS score of 1 or 0 group (n = 29) (16.6 vs. 2.9 months; p < 0.0001, respectively). Conclusions: An ECOG-PS score of 0, the absence of MVI, and TTP ≥4 months at first radiological confirmation of PD may be useful for predicting good PPS in patients with advanced HCC who do not meet the eligibility criteria for the RESORCE trial.

The impact of surgery on survival after progression of glioblastoma: A retrospective cohort analysis of a contemporary patient population

Despite updated management of glioblastoma (GB), progression is virtually inevitable. Previous data suggest a survival benefit from resection at progression; however, relatively few studies have evaluated the role of surgery in the context of contemporary GB treatment and widespread use of bevacizumab and chemotherapy. As such, the purpose of this study is to evaluate outcomes following surgical resection in patients with progressive GB since 2008. The records of all patients who underwent biopsy or resection of GB between January 1, 2008, and December 31, 2015, were retrospectively reviewed to identify 368 patients with progressive GB. Median survival and 95% confidence intervals were generated with the Kaplan-Meier method. Multivariate analysis, which controlled for age, Karnofsky Performance Status (KPS), extent of resection, adjuvant chemotherapy and radiation, tumor location, and tumor multifocality, of post-progression survival was carried out using a Cox proportional hazards model. Of 368 patients with progressive disease, 77 (20.9%) underwent resection at first documented progression. The median post-progression survivals for patients who did and did not undergo resection at this time were 12.8 and 7.0 months, respectively. In multivariate analysis, KPS ≥ 70 at progression (HR 0.438), receipt of bevacizumab at first progression (HR 0.756), and receipt of chemotherapy at first progression (HR 0.644) were associated with increased post-progression survival. Thus, surgery for progressive GB may not improve post-progression survival in the context of contemporary maximal non-surgical therapy. Further investigation is necessary to elucidate what role, if any, bevacizumab has in prolonging post-progression survival in patients with progressive GB.

Expression patterns of E2F transcription factors and their potential prognostic roles in breast cancer.

E2Fs, as a family of pivotal transcription factors, have been implicated in multiple biological functions in human cancer; however, the expression and prognostic significance of E2Fs in breast cancer remains unknown. In the present study, the mRNA expression patterns of E2Fs in breast cancer were investigated with Oncomine and The Cancer Genome Atlas data. Prognostic values of E2Fs for patients with breast cancer were determined using the Kaplan-Meier plotter database. The results strongly indicated that E2F1, E2F2, E2F3, E2F5, E2F7 and E2F8 were overexpressed in patients with breast cancer, whereas E2F4 and E2F6 exhibited no expression difference between patients with cancer and healthy controls. In survival analyses, elevated E2F1, E2F3, E2F5, E2F7 and E2F8 expression levels were significantly associated with lower overall survival, relapse-free survival (RFS), distant metastasis-free survival (DMFS) or post-progression survival for patients with breast cancer. Furthermore, high expression of E2F4 indicated improved RFS but reduced DMFS. Subgroup analyses based on four clinicopathological factors further revealed that E2Fs were associated with the prognosis of patients with breast cancer in an estrogen receptor-, progesterone receptor-, human epidermal growth factor 2- and lymph node status-specific manner. These data indicated that E2Fs may serve as promising biomarkers and therapeutic targets for breast cancer.

PS-019 - Pattern of progression determines post-progression survival in patients with hepatocellular carcinoma treated with Radioembolization

PS-019 - Pattern of progression determines post-progression survival in patients with hepatocellular carcinoma treated with Radioembolization

Prediction of post-progression survival in patients with advanced hepatocellular carcinoma treated with sorafenib by using time-dependent changes in clinical characteristics

Prediction of post-progression survival in patients with advanced hepatocellular carcinoma treated with sorafenib by using time-dependent changes in clinical characteristics

Venetoclax for Treating Chronic Lymphocytic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Venetoclax for Treating Chronic Lymphocytic Leukaemia: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.