Discordance in receptor status between primary and metastatic breast cancer and overall survival: A single-center analysis

BackgroundThe tumor phenotype may change between primary and metastatic breast cancer. We compared the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2 in a series of primary breast carcinomas (PBC) with their metastatic relapses and analyzed the impact of any changes on survival.Materials and methodsIt was a single-center retrospective study, collecting consecutive cases of metastatic breast carcinoma diagnosed in the pathology and medical oncology departments at Habib Bourguiba University Hospital in Sfax, Tunisia. An immunohistochemical study was used to assess ER, PR, and HER2 expression. Overall survival (OS) and post-metastasis survival (PMS) were evaluated using multivariable Cox regression analysis.ResultsOur study included 68 patients. ER and PR status changed in 29.4 % and 39.7 % of cases, respectively. Conversions were mainly from positive to negative status (22 % and 23.5 % for ER and PR, respectively). Differences in HER2 status were observed in 19.6 % of cases, with loss of overexpression in 6 patients (10.7 %). Adjuvant trastuzumab therapy and PBC molecular subtype (HR-, HER2+) were associated with HER2 status discordance (p = 0.02 and 0.03, respectively). On multivariable analysis, HR-negative conversion tumors were significantly associated with a worse OS (p = 0.042) and PMS (p < 0.001), compared to HR-concordant positive tumors.ConclusionThis study establishes that HR and HER2 status discordance between primary and metastatic breast carcinoma has a prognostic impact on patient outcome. Analyzing these receptors' status in all newly diagnosed cases of metastatic breast carcinoma is strongly recommended and would provide information for changing treatment strategies.     

Low BRAF and NRAS expression levels are associated with clinical benefit from DTIC therapy and prognosis in metastatic melanoma

Metastatic melanoma is characterized by a poor response to chemotherapy. Furthermore, there is a lack of established predictive and prognostic markers. In this single institution study, we correlated mutation status and expression levels of BRAF and NRAS to dacarbazine (DTIC) treatment response as well as progression-free and overall survival in a cohort of 85 patients diagnosed with advanced melanoma. Neither BRAF nor NRAS mutation status correlated to treatment response. However, patients with tumors harboring NRAS mutations had a shorter overall survival (p < 0.001) compared to patients with tumors wild-type for NRAS. Patients having a clinical benefit (objective response or stable disease at 3 months) on DTIC therapy had lower BRAF and NRAS expression levels compared to patients progressing on therapy (p = 0.037 and 0.003, respectively). For BRAF expression, this association was stronger among patients with tumors wild-type for BRAF (p = 0.005). Further, low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population (p = 0.004 and <0.001, respectively). Contrasting low NRAS expression levels, which were associated with improved overall survival in the total population (p = 0.01), low BRAF levels were associated with improved overall survival only among patients with tumors wild-type for BRAF (p = 0.013). These findings indicate that BRAF and NRAS expression levels may influence responses to DTIC as well as prognosis in patients with advanced melanoma.     

Quantified Visual Scoring of Metastatic Melanoma Patient Treatment Response Using Computed Tomography: Improving on the Current Standard

To assess whether quantitative visual scoring (QVS) is a better early predictor of progression-free survival (PFS) in patients on chemotherapy for metastatic melanoma using CT than the currently used Response Evaluation Criteria in Solid Tumors (RECIST) standard. Retrospective evaluation of 65 consecutive patients with metastatic melanoma on treatment who had a baseline and follow-up CT after two cycles of therapy. QVS was used to code imaging findings on the radiology reports considering size change, brain metastases, new lesions, mixed lesion response, and the number of organ systems involved. RECIST 1.1 criteria placed patients in the progressive disease, stable disease, or partial response groups. Multiple regression analysis was used to correlate the various independent variables with PFS. The Cox hazard proportions ratio, median survival, and Kaplan–Meier curves of the different prognostic groups were calculated. QVS of size change was found more sensitive in detecting patients deteriorating (57.1% versus 37.5%) or improving (23.8% versus 10.7%), more correlated with the median PFS for the deteriorating (1.8 versus 1.7 months), stable (5.6 versus 4.0 month), and improving (8.3 versus 5.5 months) categories and more predictive of PFS (Cox hazard proportion ratio of 3.070 versus 1.860) than RECIST 1.1 categorization. Multiple regression analysis demonstrated QVS of lesion size correlated most closely with PFS among the variables assessed (r = 0.519, p < 0.0001). QVS in this study was superior to standard RECIST categorization in terms of discriminating treated metastatic melanoma patients likely to have longer PFS.     

Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer

PurposeTo determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis.ResultsThe CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS).ConclusionAmong well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.     

Non-Myeloablative Allogeneic Transplantation with Post-Transplant Cyclophosphamide after Immune Checkpoint Inhibition for Classic Hodgkin Lymphoma: A Retrospective Cohort Study

Immune checkpoint inhibitors (ICIs) are approved in relapsed classic Hodgkin lymphoma (cHL). The safety and effectiveness of allogeneic blood or marrow transplantation (alloBMT) in ICI-pretreated patients with cHL remain unclear. The aim of this study is to assess outcomes of patients with cHL receiving ICIs before alloBMT using post-transplantation cyclophosphamide (PTCy) graft-versus-host-disease (GVHD) prophylaxis.We performed a retrospective study of relapsed/refractory patients with cHL undergoing alloBMT with PTCy at Johns Hopkins between November 2004 and September 2019. Engraftment, GVHD incidence, nonrelapse mortality, progression-free survival (PFS), and overall survival (OS) were compared between patients receiving pre-alloBMT ICI or standard salvage chemotherapy.We identified 105 consecutive relapsed/refractory patients with cHL, of whom 37 (35.2%) received ICIs and 68 (64.7%) received chemotherapy without ICIs (no-ICI) before alloBMT. ICI and no-ICI patients experienced a 3-year estimated OS of 94% versus 78% (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.08 to 1.56; P = .17) and a 3-year estimated PFS of 90% and 65% (HR, 0.3; 95% CI, 0.09 to 1; P = .05), respectively. We observed no statically significant difference in the 12-month cumulative incidence of acute grade II to IV GVHD or in the 24-month incidence of chronic GVHD.ICIs do not increase acute or chronic GVHD incidence compared with salvage chemotherapy. Patients with cHL receiving ICIs prior to alloBMT experienced outstanding PFS and OS. Thus, ICI therapy is safe in patients with cHL when undergoing alloBMT with PTCy and may improve post-alloBMT disease progression and survival.     

Prognostic significance of intrahepatic lymphatic invasion in colorectal liver metastases

BackgroundIntrahepatic lymphatic invasion is an adverse prognostic factor after hepatectomy for colorectal liver metastases (CLMs). However, most patients in previous reports had liver resection before the era of FOLFOX/FIRI-based chemotherapy.MethodsForty-six patients who underwent hepatectomy for CLMs from 2004 to 2020 were evaluated. We histologically evaluated portal invasion, intrahepatic lymphatic invasion, and biliary invasion on hematoxylin-eosin slides. We also collected the following clinicopathologic factors: gender, age, timing, the number and maximum size of CLMs, preoperative tumor markers, neutrophil/lymphocyte ratio, location, and lymph node metastases of primary cancer, and chemotherapy after hepatectomy. A multivariate Cox proportional hazard model was used to define the relationship between overall (OS) or disease-free survival (DFS) and clinicopathologic factors.ResultsHistological invasions were portal invasion in 8 (17.4 %), intrahepatic lymphatic invasion in 6 (13.0 %), and biliary invasion in 5 (10.9 %). Chemotherapy for recurrence after hepatectomy (n = 29) was performed in 22 and 14 of those who received FOLFOX/FIRI-based chemotherapy. By multivariate analysis, the number of CLMs (p < 0. 01) and presence of intrahepatic lymphatic invasion (p = 0.02) were independent predictors of recurrence. The number of CLMs (p = 0.02) and prehepatectomy carcinoembryonic antigen level (p = 0.02), but not intrahepatic lymphatic invasion (p = 0.18), were independent predictors of survival using multivariate analysis.ConclusionsThe presence of intrahepatic lymphatic invasion adversely affected patient's DFS, but not OS in patients with CLMs in the era of FOLFOX/FIRI chemotherapy. FOLFOX/FIRI-based chemotherapy might improve OS, even in patients with positive intrahepatic lymphatic invasion.     

Association between carbonic anhydrase 9 expression and poor prognosis in sinonasal squamous cell carcinoma

ObjectivesCarbonic anhydrase 9 (CA9), as a member of the carbonic anhydrase enzyme family, was an endogenous marker of hypoxia. Previous studies suggested CA9 expression was correlated with poor prognosis in multiple types of malignancies. Therefore, this study was to evaluate the role of CA9 in sinonasal squamous cell carcinoma (SNSCC) and to determine whether this biomarker was associated with patient clinicopathologic characteristics and prognosis.MethodsWe assessed 63 patients diagnosed with SNSCC in 2013–2017 who underwent curative surgery. Tumor specimens was immunohistochemically analyzed for CA9 expression. The expression levels of CA9 was evaluated in relation to clinicopathological factors and prognosis.ResultsPositive expression of CA9 was observed in 21 (33.3%) patients and was significantly correlated with local recurrence (p = 0.016), overall survival (OS) (p = 0.003) and disease-free survival (DFS) (p = 0.002). In Cox's multivariate analysis, CA9 expression was an independent negative prognostic factor for OS (p = 0.048) and DFS (p = 0.019).ConclusionsOur findings demonstrated that CA9 overexpression could be used as an independent prognostic biomarker and therapeutic target in SNSCC.     

LncRNA PCAT6: A potential biomarker for diagnosis and prognosis of bladder cancer

BackgroundMany potential biomarkers have been identified and studied for bladder cancer diagnosis. In this study, we investigated the role of a new biomarker, long noncoding RNA (lncRNA) PCAT6, in bladder cancer diagnosis and prognosis.Methods and resultsThe lncRNA PCAT6 expression profile of BC is analyzed using the Cancer Genome Atlas Urothelial Bladder Carcinoma (TCGA-BLCA) data. PCAT6 expression level in 106 pairs of BC tissues and adjacent normal tissues was detected and compared using qRT-PCR. Then, the association between PCAT6 expression and clinicopathologic indicators of BC was evaluated. Meanwhile, the prognostic value of PCAT6 was tested using Kaplan-Meier analysis. Additionally, loss-of-function assays were used to explore the effect of PCAT6 on the biological function of BC cells.We identified that the expression level of PCAT6 in BC tissue was higher than that in adjacent normal tissues. And the BC patients have higher serum PCAT6 than that in healthy volunteers. In addition, the expression level of PCAT6 was correlated with tumor size (p = 0.005), differentiation (p = 0.018), TNM stage (p = 0.04), lymph nodes metastasis (p = 0.019), and distant metastasis (p = 0.028). Kaplan-Meier analysis showed that BC patients with high PCAT6 expression had shorter overall survival (OS) and progression-free survival (PFS). The loss-of-function results revealed that the proliferation and viability of BC cells in PCAT6 knockdown groups decreased significantly, compared with the negative control groups.ConclusionOur results demonstrated that PCAT6 might be a potential biomarker for diagnosis and prognosis of BC.     

Tandem Autologous-Autologous versus Autologous-Allogeneic Hematopoietic Stem Cell Transplant for Patients with Multiple Myeloma: Long-Term Follow-Up Results from the Blood and Marrow Transplant Clinical Trials Network 0102 Trial

Allogeneic hematopoietic cell transplant (HCT) may improve long-term multiple myeloma (MM) control through the graft-versus-myeloma effect. The Blood and Marrow Transplant Clinical Trials Network 0102 trial was a biologic assignment trial comparing tandem autologous transplant (auto-auto) versus autologous followed by reduced-intensity allogeneic (auto-allo) transplant in patients with newly diagnosed MM with standard-risk (n = 625) or high-risk (n = 85; β₂-microglobulin at diagnosis ≥ 4 mg/dL or deletion of chromosome 13 by conventional karyotyping) disease. Although the initial 3-year analysis showed no difference in progression-free survival (PFS) between arms in either risk group, we hypothesized that long-term follow-up may better capture the impact of the graft-versus-myeloma effect. Median follow-up of survivors was over 10 years. Among standard-risk patients there was no difference in PFS (hazard ratio [HR], 1.11; 95% confidence interval [CI], .93 to 1.35; P = .25) or OS (HR, 1.03; 95% CI, .82 to 1.28; P = .82). The 6-year PFS was 25% in the auto-auto arm versus 22% in the auto-allo arm (P = .32), and 6-year overall survival (OS) was 60% and 59%, respectively (P = .85). In the high-risk group, although there was no statistically significant difference in PFS (HR, .66; 95% CI, .41 to 1.07; P = .07) and OS (HR, 1.01; 95% CI, .60 to 1.71; P = .96), a reduction in 6-year risk of relapse of 77% versus 47% (P = .005) was reflected in better PFS of 13% versus 31% (P = .05) but similar OS, at 47% versus 51% (P = .69). Allogeneic HCT can lead to long-term disease control in patients with high-risk MM and needs to be explored in the context of modern therapy.     

Impact of Pretransplantation Conditioning Regimens on Outcomes of Allogeneic Transplantation for Chemotherapy-Unresponsive Diffuse Large B Cell Lymphoma and Grade III Follicular Lymphoma

Patients with chemorefractory non-Hodgkin lymphomas generally have a poor prognosis. We used the observational database of the Center for International Blood and Marrow Transplant Research to study the outcome of 533 patients with refractory diffuse large B cell lymphoma (DLBCL) or grade III follicular lymphoma (FL-III) who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA; n = 307) or reduced-intensity/nonmyeloablative conditioning (RIC/NST; n = 226) between 1998 and 2010. We analyzed nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Only 45% of the patients at transplantation had a Karnofsky performance score of ≥90%. Median follow-up of surviving patients after MA and RIC/NST allo-HCT is 35 months and 30 months, respectively. At 3 years, MA allo-HCT was associated with a higher NRM compared with RIC/NST (53% versus 42%; P = .03), similar PFS (19% versus 23%; P = .40), and lower OS (19% versus 28%; P = .02), respectively. On multivariate analysis, FL-III histology was associated with lower NRM (relative risk [RR], .52), reduced risk of relapse/progression (RR, .42), and superior PFS (RR, .51) and OS (RR, .53), whereas MA conditioning was associated with reduced risk of relapse/progression (RR, .66). Despite a refractory state, a small subset of DLBCL and FL-III patients can attain durable remissions after allo-HCT. Conditioning regimen intensity was not associated with PFS and OS despite a higher risk of relapse/progression with RIC/NST allo-HCT.     

Induction chemotherapy plus nimotuzumab followed by concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma

IntroductionThis study investigated the best mode for the application of nimotuzumab (Nimo) in combination with chemoradiotherapy to treat nasopharyngeal carcinoma (NPC).Material and methodsData were prospectively collected from 168 patients with NPC from September 2009 to February 2014. One hundred twelve patients received 2–3 cycles of induction chemotherapy (IC) followed by concurrent chemoradiotherapy (CCRT), and 56 patients with well-matched propensity scores received IC + CCRT + Nimo. Patients were divided into 3 subgroups according to the application schedule of Nimo: group A, IC + CCRT; group B: IC (combined with Nimo) + CCRT; and group C: IC + CCRT (combined with Nimo). The 5-year overall survival (OS) and progression-free survival (PFS) and adverse events were investigated.ResultsWith a median follow-up of 61.4 months (range: 1.7–96.5 months), the 5-year OS and PFS for group A vs. groups B + C were 74.8 ±4.1% versus 87.0 ±4.6% (p = 0.043) and 72.7 ±4.3% vs. 83.1 ± 5.1% (p = 0.243), respectively. The 5-year OS of group B was significantly improved over that of group A (93.0 ±4.8% vs. 74.8 ±4.1%, p = 0.038); however, there was no benefit to the 5-year PFS (89.3 ±5.9% vs. 72.7 ±4.3%, p = 0.144). The 5-year OS and PFS for group C were 80.4 ±7.9% and 76.4 ±8.5%, respectively, and there was no statistically significant difference from group A (p = 0.257 and p = 0.611, respectively). No significant increase in toxicities was observed with the addition of Nimo.ConclusionsNimo administered with chemoradiotherapy is effective for NPC. Nimo concurrent with IC followed by CCRT could be the optimal mode of sequential treatment.     

Impact of Donor Source on Allogeneic Hematopoietic Stem Cell Transplantation for Mature T Cell and Natural Killer Cell Neoplasms in the Kyoto Stem Cell Transplantation Group

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the key strategy to cure patients with mature T and natural killer (NK) cell lymphomas/leukemia, especially those with relapsed/refractory diseases, there is no consensus strategy for donor selection. We retrospectively analyzed the outcomes of allo-HSCT in 111 patients in 15 Japanese institutions as a multi-institutional joint research project. Thirty-nine patients received bone marrow or peripheral blood stem cell transplantation from related donors (rBMT/rPBSCT), 37 received BMT/PBSCT from unrelated donors (uBMT/uPBSCT), and 35 received cord blood transplantation (CBT). Overall survival (OS) and progression-free survival (PFS) at 4 years were 42% and 34%, respectively. The cumulative incidences of relapse and nonrelapse mortality were 43% and 25%. In multivariate analysis, CBT showed comparable OS with rBMT/rPBSCT (rBMT/rPBSCT versus CBT: hazard ratio [HR], 1.63; P = .264) and better OS compared with uBMT/uPBSCT (HR, 2.99; P = .010), with a trend toward a lower relapse rate (rBMT/rPBSCT versus CBT: HR, 2.60; P = .010; uBMT/uPBSCT versus CBT: HR, 2.05; P = .082). This superiority of CBT was more definite in on-disease patients (OS: rBMT/rPBSCT versus CBT: HR, 5.52; P = .021; uBMT/uPBSCT versus CBT: HR, 6.80; P = .007). Better disease control was also strongly associated with better OS and PFS with lower relapse rate. In conclusion, allo-HSCT is beneficial for the survival of patients with mature T and NK cell lymphomas/leukemia if performed in a timely fashion. Since CBT showed favorable survival with a lower relapse risk, it could be a preferred alternative, especially in on-disease patients.     

The expression of programmed death-ligand 1 and programmed death-ligand 2 in endometrial carcinosarcoma: Correlation with mismatch repair protein expression status,tumor-infiltrating lymphocyte infiltration,and clinical outcomes

BackgroundEndometrial carcinosarcomas have high malignant potential with a high recurrence rate and poor prognosis. Immunotherapy may be a promising treatment option. The aim of this study is to evaluate the expression of PD-L1/PD-L2 and its relationship to mismatch repair (MMR) protein status and tumor-infiltrating lymphocyte (TIL) density.MethodsWe performed immunohistochemical analyses of PD-L1 (clone 22C3), PD-L2 (clone TY25), MSH-2, MSH-6, PMS-2, and MLH-1 in 77 tumors. We count TILs using CD8 antibody. Clinicopathologic features were recorded and statistically correlated with immunohistochemical results. Kaplan-Meier analyses were used to analyze the prognosis.ResultsWhile PD-L1 positivity was seen more commonly in MMR protein deficient tumors (p = 0.010), PD-L2 positivity was seen more commonly in MMR protein proficient tumors (p = 0.003). PD-L1 positivity was also found to be more common in carcinosarcoma with high TIL infiltration. PD-L2 positivity was associated with decreased overall survival (OS) rates (p = 0.043, p = 0.043, respectively), whereas the PD-L1 positivity and TIL density were not significantly associated with OS rate. The OS rate of patients with MMR protein proficient tumors was significantly lower compared with those with MMR protein deficient tumors (p = 0.042). The lower TILs infiltration was associated with a shorter disease-free survival (DFS) rate. PD-L1 and PD-L2 positivity did not affect the DFS rate.ConclusionsPD-L1/PD-L2 might be a better target for immunotherapy in endometrial carcinosarcoma. PD-L2 positivity was also associated with a worse clinical outcome in patients with endometrial carcinosarcoma, suggesting that PD-L2 status can be used to predict clinical behavior. Further studies are needed to elucidate the relationship between PD-L1/PD-L2 expression and therapeutic response.     

Gemcitabine and Erlotinib with or without Oxaliplatin in Previously Untreated Advanced Pancreatic Cancer: A Randomized Phase II Trial

PurposeErlotinib has been the only targeted agent to show significantly improved outcomes in pancreatic adenocarcinoma when combined with gemcitabine. We aimed to evaluate whether the addition of oxaliplatin to a combination gemcitabine/erlotinib treatment conferred a clinical benefit in patients with locally advanced unresectable or metastatic pancreatic cancer.Materials and MethodsChemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T [gemcitabine 1000 mg/m² and oxaliplatin 50 mg/m² on day 1 (D1) and D8 plus erlotinib 100 mg daily for 3 weeks] or GT (gemcitabine 1000 mg/m² on D1 and D8 plus erlotinib 100 mg daily for 3 weeks). The primary endpoint was the overall response rate (ORR).ResultsBetween 2013 and 2016, 65 patients were assigned to a treatment group (33 in the GEMOX-T arm, 32 in the GT arm). The ORR was 18.2% [95% confidence interval (CI), 8.82–27.58] in the GEMOX-T arm and 6.2% (95% CI, 0.34–12.06) in the GT arm (p=0.051). The disease control rate was significantly superior in the GEMOX-T arm compared to the GT arm (72.7% vs. 43.8%, p=0.019). After a median follow-up of 19.7 months, the median progression-free survival (PFS) was 3.9 months for the GEMOX-T arm and 1.4 months for the GT arm (p=0.033). However, this did not translate to an improvement in overall survival. The most common grade 3 or higher hematologic adverse events were neutropenia (16.9%) and anemia (13.8%).ConclusionThe addition of oxaliplatin to a first-line gemcitabine/erlotinib regimen demonstrated higher response rates and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.     

Allogeneic Hematopoietic Cell Transplantation for Chemotherapy-Unresponsive Mantle Cell Lymphoma: A Cohort Analysis from the Center for International Blood and Marrow Transplant Research

Patients with chemorefractory mantle cell lymphoma (MCL) have a poor prognosis. We used the Center for International Blood and Marrow Transplant Research database to study the outcome of 202 patients with refractory MCL who underwent allogeneic hematopoietic cell transplantation (allo-HCT) using either myeloablative (MA) or reduced-intensity/nonmyeloablative conditioning (RIC/NST), during 1998-2010. We analyzed nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS). Seventy-four patients (median age, 54 years) received MA, and 128 patients (median age, 59 years) received RIC/NST. Median follow-up after allo-HCT was 35 months in the MA group and 43 months in the RIC/NST group. At 3 years post-transplantation, no significant between-group differences were seen in terms of NRM (47% in MA versus 43% in RIC/NST; P = .68), relapse/progression (33% versus 32%; P = .89), PFS (20% versus 25%; P = .53), or OS (25% versus 30%; P = .45). Multivariate analysis also revealed no significant between-group differences in NRM, relapse, PFS, or OS; however, receipt of a bone marrow or T cell–depleted allograft was associated with an increased risk of NRM and inferior PFS and OS. Our data suggest that despite a refractory disease state, approximately 25% of patients with MCL can attain durable remission after allo-HCT, and conditioning regimen intensity does not influence outcome of allo-HCT.     

Efficacy of high-dose corticosteroid-based treatment for chronic lymphocytic leukemia patients with p53 abnormalities in the era of B-cell receptor inhibitors

PurposeHigh-dose methylprednisolone (HDMP) with or without anti-CD20 antibody treatment in the pre B-cell receptor inhibitor (BCRi) era was used as potential salvage therapy for relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (r/r CLL/SLL) patients bearing the 17p deletion.Patients and methodsOutcomes were compared in retrospect between r/r patients treated with HDMP (n = 20), ibrutinib (n = 39) and idelalisib with rituximab (n = 14).ResultsHigher overall response rates were found in those patients undergoing BCRi therapy compared to HDMP (79.2% vs. 0%; p < 0.0001), along with longer median progression-free survival (not reached vs. 24.1 months; p < 0.01). Nevertheless, there were no differences in the overall survival (HDMP 35.87 months vs. not reached; p = 0.58).ConclusionHDMP treatment was significantly inferior in terms of response rate and progression-free survival in r/r CLL/SLL patients with the 17p deletion, and may only be used whenever novel compounds are unavailable.     

The expression of long non-coding RNA HOTAIR in advanced hepatocellular carcinoma and its prognostic correlation with sunitinib therapy

IntroductionThe study was designed to assess the expression of long non-coding RNA HOTAIR (lncRNA HOTAIR) in tissues and peripheral blood of patients with advanced hepatocellular carcinoma (HCC). In addition, we also investigated the prognostic correlation between the expression level of lncRNA HOTAIR in tumour tissues and peripheral blood of patients with advanced HCC and sunitinib monotherapy.Material and methodsA total of 60 patients with advanced HCC who received sunitinib monotherapy and another 60 healthy individuals who were examined at the physical examination centre during the same period were included in the study. Real-time quantitative PCR (RT-QPCR) was used to determine the relative expression of lncRNA HOTAIR in tumour tissue, adjacent tissue, and peripheral blood of HCC patients as well as peripheral blood of healthy controls. Moreover, the clinicopathological information, overall survival (OS), and progression-free survival (PFS) were collected, followed by correlation analysis with lncRNA HOTAIR expression.ResultsThe expression of lncRNA HOTAIR was significantly higher in tumour tissues compared to that in adjacent tissues (t = 9.03, p < 0.001). The expression of lncRNA HOTAIR in peripheral blood of HCC patients was higher than that in healthy controls (t = 8.04, p < 0.001). There was a correlation between the expression of lncRNA HOTAIR in tumour tissue and peripheral blood in HCC patients (r = 0.638, p < 0.001). Patients with low lncRNA HOTAIR expression in tumour tissues harboured significantly longer OS (13.4 vs. 9.5, p < 0.001) and PFS (8.4 vs. 6.2, p < 0.001) compared to those with high expression. Consistently, patients with low lncRNA HOTAIR expression in peripheral blood had significantly prolonged OS (12.8 vs. 9.1, p < 0.001) and PFS (8.9 vs. 6.4, p < 0.001) compared to those with high expression. Patients with low expression both in tumour tissue and peripheral blood had prolonged OS (14.3 vs. 8.8, p < 0.001) and PFS (10.6 vs. 6.0, p < 0.001) compared to the rest of the patients. Cox regression analysis indicated that the expression level of lncRNA HOTAIR in tumour tissue and peripheral blood was an independent predictive factor of OS and PFS in patients with advanced HCC treated by sunitinib.ConclusionsThe expression of lncRNA HOTAIR was up-regulated in tumour tissue and peripheral blood in patients with advanced HCC. In addition, the expression level of lncRNA HOTAIR was one of the indicators predicting the effectiveness of sunitinib therapy.     

Prognostic Factors for Recurrence and Progression in Korean Non-Muscle-Invasive Bladder Cancer Patients: A Retrospective,Multi-Institutional Study

PurposeTo identify the prognostic factors related to tumor recurrence and progression in Korean patients with non-muscle-invasive bladder cancer (NMIBC).ResultsWith a median follow-up duration of 37 months, 866 patients (35.9%) experienced recurrence, and 137 (5.7%) experienced progression. Patients with recurrence had a median time to the first recurrence of 10 months. Multivariable analysis conducted in all patients revealed that preoperative positive urine cytology (PUC) was independently associated with worse recurrence-free survival [RFS; hazard ratio (HR) 1.56; p<0.001], and progression-free survival (PFS; HR 1.56; p=0.037). In particular, on multivariable analysis conducted for the high-risk group (T1 tumor/high-grade Ta tumor/carcinoma in situ), preoperative PUC was an independent predictor of worse RFS (HR 1.73; p<0.001) and PFS (HR 1.96; p=0.006). On multivariable analysis in patients with T1 high-grade (T1HG) cancer (n=684), better RFS (HR 0.75; p=0.033) and PFS (HR 0.33; p<0.001) were observed in association with the administration of intravesical Bacillus Calmette-Guérin (BCG) induction therapy.ConclusionA preoperative PUC result may adversely affect RFS and PFS, particularly in high-risk NMIBC patients. Of particular note, intravesical BCG induction therapy should be administered as an adjunct to TURBT in order to improve RFS and PFS in patients with T1HG cancer.     

Pretreatment Levels of Vascular Endothelial Growth Factor in Plasma Predict a Complete Remission Rate and Time to Relapse or Progression in Patients with Diffuse Large B-Cell Lymphoma

The aim of this study was to verify whether pretreatment plasma levels of vascular endothelial growth factor (VEGF) correlate with prognosis and survival of patients with diffuse large B-cell lymphoma (DLBCL). Plasma VEGF levels were assessed at the time of diagnosis in 157 DLBCL patients treated with anthracycline-based chemotherapy. Plasma VEGF levels greater than or equal to the highest quartile (high VEGF levels) were associated with lower probability of a complete remission achievement (odds ratio 0.3; 95 % confidence interval [CI]: 0.1–0.6; p = 0.002) in univariate as well as in multivariate analysis (p = 0.04). The estimated 3-year progression-free survival (PFS) rate of patients with high VEGF levels was 31.7 % (95 % CI 17–51) compared to the 62.5 % 3-year PFS rate (95 % CI 53–71; p = 0.0004) in the patients with lower values. The former group of patients demonstrated an estimated 3-year overall survival (OS) rate of 47.1 % (95 % CI 30–65) in contrast to the 3-year OS rate of 64.3 % (95 % CI 54–73; p = 0.02) in the latter. In multivariate analysis, the high VEGF level retained its independent impact on shorter PFS (p = 0.02). Our results suggest that VEGF plays an important role in the clinical course of DLBCL. VEGF may be a useful marker for selecting the patients for whom new treatment approaches, especially those based on VEGF inhibitors, could be recommended.     

Re-Irradiation for Recurrent Gliomas: Treatment Outcomes and Prognostic Factors

PurposeThe aim of this study was to evaluate the efficacy of re-irradiation in patients with recurrent gliomas and to identify subgroups for whom re-irradiation for recurrent gliomas is most beneficial.ResultsMedian doses of re-irradiation and initial RT were 45.0 Gy and 59.4 Gy, respectively. The median time interval between initial RT and re-irradiation was 30.5 months. Median overall survival (OS) and the 12-month OS rate were 11 months and 41.7%, respectively. In univariate analysis, Karnofsky performance status (KPS) ≥70 (p<0.001), re-irradiation dose ≥45 Gy (p=0.040), and longer time interval between initial RT and re-irradiation (p=0.040) were associated with improved OS. In multivariate analysis, KPS (p=0.030) and length of time interval between initial RT and re-irradiation (p=0.048) were important predictors of OS. A radiographically suspected mixture of radiation necrosis and progression after re-irradiation was seen in 5 patients.ConclusionRe-irradiation in conjunction with surgery could be a salvage treatment for selected recurrent glioma patients with good performance status and recurrence over a long time.