Significant Prognostic Factors For Overall Survival Research Articles

Omission of Chemotherapy for the Treatment of Mucinous Breast Cancer: A Nationwide Study from the Korean Breast Cancer Society.

PurposeMucinous breast carcinoma (MBC) is a rare type of breast cancer. Although patients with MBC may have a better prognosis than that of patients with invasive ductal carcinoma, many clinicians administer adjuvant chemotherapy regimens similar to those for other breast tumors. Using data from a nationwide clinical database, this study evaluated the significance of adjuvant systemic chemotherapy and whether it can be omitted in MBC patients.MethodsWe included 3,076 patients with a diagnosis of MBC recorded in the Korean Breast Cancer Registry between January 1990 and August 2016. We used the Kaplan-Meier method to analyze breast cancer-specific survival (BCCS) and overall survival (OS). Multivariate analysis was performed using a Cox proportional hazard ratio (HR) model to estimate the adjusted HR for each prognostic factor.ResultsA total of 2,988 MBC patients were enrolled and followed-up for a median of 100 months (range, 2–324 months). Multivariate analysis revealed that axillary lymph node (ALN) metastasis and estrogen receptor (ER) negativity were significant prognostic factors for BCSS. Meanwhile, old age, pathologic tumor stage, and ALN metastasis were significant prognostic factors for OS. Subgroup analysis of ER-positive MBC showed that ALN metastasis was a significant prognostic factor for BCSS. Additionally, old age, pathologic tumor stage, and ALN metastasis were prognostic factors for OS. Ultimately, ALN metastasis was the most statistically significant prognostic factor for MBC. However, chemotherapy had no significant effect on BCSS and OS. The Kaplan-Meier curves of BCSS and OS based on pathologic tumor and nodal stages and age revealed that chemotherapy did not statistically significantly improve prognosis, except for the N3 stage.ConclusionOur large retrospective analysis revealed that adjuvant chemotherapy provided little benefit to improve the prognosis of most ER-positive MBC patients. Therefore, chemotherapy can be omitted in the treatment of most ER-positive MBC.

Value of radiotherapy in addition to esophagectomy for stage II and III thoracic esophageal squamous cell carcinoma: Analysis of surveillance, epidemiology, and end results database

To determine the value of radiotherapy in addition to esophagectomy for stage II and III TESCC. We searched the Surveillance, Epidemiology, and End Results (SEER) database for all cases of stage II‐III TESCC. Patients were grouped as those receiving pre‐ or postoperative radiotherapy plus esophagectomy and those receiving esophagectomy alone. Overall survival (OS) and cancer‐specific survival (CSS) were compared between the groups. Among the 3292 patients, multimodality treatments (pre‐ or postoperative radiotherapy plus surgery) were more effective than surgery alone (5‐year, OS: 17.3% vs 7.9%; P < 0.001; CSS: 51.8% vs 34.9%; P < 0.001). Among the patients receiving multimodality treatments, multivariate analyses revealed stage to be the most significant prognostic factor for OS (II vs III, HR, 0.726; P < 0.001), but the sequence of radiotherapy and surgery was only of the marginal significance (pre‐ vs postoperative, HR, 0.875; P = 0.093). Preoperative radiotherapy provided significantly better survival than postoperative radiotherapy in stage III disease (5‐year, OS: 13.0% vs 11.0%, P < 0.04; CSS: 49.2% vs 31.7%, P < 0.003), but not in stage II disease (5‐year OS: 23.5% vs 21.0%, P = 0.519; CSS: 62.0% vs 53.4%, P = 0.075). Radiotherapy in addition to esophagectomy provides better outcomes than esophagectomy alone for in stage II‐III TESCC. Preoperative radiotherapy followed by surgery appears to be the optimal treatment strategy in stage III TESCC.

Factors improving the outcome of patients re-irradiated with intensity-modulated radiotherapy (IMRT) for relapse or new head and neck cancer developed in irradiated areas.

Patients with secondary/recurrent squamous cell head and neck cancer have poor prognoses. Re-irradiation is a treatment option. However, best technique to re-irradiate is not known. This study aims to evaluate the outcome of patients treated with curative-intent intensity-modulated radiotherapy (IMRT) re-irradiation (re-RT) for head and neck (H&N) cancers. Fifty patients with recurrent H&N cancers underwent fractionated IMRT re-RT. The median time between the two courses of radiotherapy was 22 months. The median dose of re-RT was 66 Gy. The median follow-up of surviving patients was 13.6 months. The median overall survival (OS) was 15.7 months, and the 1- and 2-year OS rates were 62.4% and 33.9%, respectively. On multivariate analysis, performance status (PS) 0-1 (HR, 0.518; 95% CI: 0.292-0.917; P=0.024) and 3D-RT use during the first irradiation course technique (HR, 0.415; 95% CI: 0.183-0.938; P=0.035) were favorable, independent of significant prognostic factors of OS. The median loco-regional progression-free survival (LRPFS) was 8.3 months, and, the 1- and 2-year LRPFS rates were 46.6% and 35.9%, respectively. On multivariate analysis, a surgical resection before re-RT (HR, 0.107; 95% CI: 0.027-0.428; P=0.002), a higher age (HR, 0.894; 95% CI: 0.833-0.960; P=0.002), a PS 0-1 (HR, 0.316; 95% CI: 0.140-0.715; P=0.006), and a long re-RT interval (HR, 0.970; 95% CI: 0.945-0.996; P=0.024) were favorable independent significant prognostic factors of LRPFS. The median progression-free survival (PFS) was 7.0 months and, the 1- and 2-year PFS rates were 45.0% and 30.4%, respectively. On multivariate analysis, a surgical resection before re-RT (HR, 0.129; 95% CI: 0.036-0.466; P=0.002), a PS 0-1 (HR, 0.399; 95% CI: 0.208-0.764; P=0.006) and, a long re-RT interval (HR, 0.958; 95% CI: 0.927-0.989; P=0.009) were favorable, independent significant prognostic factors. The early and late toxicities rates were 28% and 34%, respectively. Re-RT for H&N cancers can be curative, and the complications can be manageable but patients need to be strictly selected. Surgery before re-RT could improve the patient outcome. Dose and irradiation schedules should be prospectively evaluated.

Survival nomograms for stage III colorectal cancer.

The postoperative survival of patients with stage III colorectal cancer (CRC) various obviously. We sought to develop novel nomograms for predicting the survival of these patients after radical surgery and postoperative chemotherapy.A total of 620 consecutive patients with stage III CRC who underwent curative resection and postoperative chemotherapy between January 2009 and December 2015 were retrospectively collected and randomly allocated to the training (n = 372) or validation cohort (n = 248). Clinicopathological factors were collected and analyzed. On the basis of data from 372 patients in the training set, predictive factors for overall survival (OS) and disease-free survival (DFS) were identified using multivariate Cox regression and used to construct nomograms. The predictive performance of the nomograms was assessed by concordance index (C-index) and calibration plots. An external cohort of 248 patients was used to validate the nomograms. Furthermore, nomogram performance was compared with the performance of T and N stage stratification.Tumor differentiation grade, lymph node metastasis ratio, intravascular emboli (IVE), preoperative serum carcinoembryonic antigen (CEA) level, albumin to globulin ratio (AGR), T stage and N stage were significant prognostic factors for OS on multivariate analysis; whereas, Tumor differentiation grade, lymph node metastasis ratio, IVE, AGR and N stage were significant for DFS. Nomograms to predict 3- and 5-year OS and DFS were established that performed well (C-indexes of 0.734 [95% CI, 0.691–0.779] for OS and 0.699 [95% CI, 0.657–0.740] for DFS prediction), and nomogram accuracy was confirmed in the validation cohort. Furthermore, model comparison proved that the nomograms were superior to risk stratification by T and N stage for stage III CRC.We propose 2 practical nomograms for stage III CRC patients that provide more accurate prognostic predictions and should be helpful for guiding individualized treatment and postoperative surveillance.

Prognostic value of the fibrinogen-to-platelet ratio as an inflammatory and coagulative index in patients with gastric cancer

We assessed the prognostic value of the fibrinogen-to-platelet ratio (FPR) as an inflammatory and coagulative index by examining its clinicopathologic and prognostic efficiency in patients with gastric cancer (GC). The subjects of this retrospective study were 182 GC patients whose FPR was measured preoperatively between January, 2001 and December, 2006. The FPR was defined as the plasma fibrinogen divided by the platelet counts. Patients aged ≥ 65years and with venous invasion had a significantly higher FPR (p = 0.02 and p < 0.01, respectively) than those aged < 65years and without venous invasion. We found a correlation between the FPR and all recurrences (p < 0.01). Patients with a low FPR had significantly better overall survival (OS) and relapse-free survival (RFS) rates than patients with a high FPR (p = 0.001 for both). Furthermore, the FPR was an independent predictor of OS and RFS (p = 0.02 and 0.001, respectively), but the fibrinogen level was not. In a subgroup analysis, the FPR was a significant prognostic factor for OS and RFS in patients with pathological stages II/III disease and in patients aged < 65years. The FPR can be calculated easily and is more useful than the fibrinogen level for predicting the prognosis of GC patients. Patients with a high FPR, particularly those with undifferentiated tumors, those with pStage II/III disease, and those aged < 65 years, require more intensive chemotherapy.

Clinical Outcomes and Prognostic Factors in Limited-Stage Small Cell Lung Cancer Patients Treated with Intensive Modified Radiation Therapy

To investigate the clinical effect of combined modality treatment and examine the prognostic factors for overall survival (OS) in limited-stage small cell lung cancer (LS-SCLC) on the base of intensive modified radiotherapy (IMRT). A retrospective analysis was performed on the clinical data of 484 LS-SCLC patients treated with chemotherapy and IMRT in our centre from August 2006 to May 2014. All patients were primarily managed with concurrent or sequential chemoradiotherapy, followed by prophylactic cranial irradiation (PCI) in patients with complete or partial response. IMRT was adopted in all patients with a median radiation dose 60Gy (2Gy once daily over 6 weeks). Kaplan-Meier method was used for survival analysis, and Log-rank test and Cox regression were used for univariate and multivariate analysis of prognostic factors. Follow-up rate was 93%. The median survival time(MST) was 23.8 months (95%CI 20.3-27.4), and the 2-,3-, and 5-year OS were 48.7%,39.8%, and 28.6%, respectively. The median progression-free survival time(PFS) was 14.1 months (95%CI 12.6-15.5), and the 2-,3-, and 5-year PFS were 34.4%, 30.5%, and 28.3%, respectively. The acute toxicity after chemotherapy and thoracic IMRT was tolerable. The acute toxicities included grade ≥3 hematological toxicity, grade ≥2 radiation esophagitis and grade ≥2 pneumonitis, which occurred in 26.9%, 24.8%, and 18.4% of all patients. The rates of CR, PR, SD, PD after thoracic radiation were 15.5%, 69.0%, 5.6%, 7.0%, respectively. Response information of 14 patients were lost and objective response rate was 84.5%. The univariate analysis showed that age, smoking history, TNM stage, PCI and the number of induction chemotherapy cycles were significant prognostic factors for OS of LS-SCLC (P=0.006, 0.001, 0.047, <0.001,0.046). The multivariate analysis showed that smoking history and PCI were independent factors affecting the prognosis for the LS-SCLC patients (P=0.001, <0.001). Combined chemotherapy and thoracic IMRT achieved satisfactory clinical outcomes and mild toxicity in LS-SCLC. Smoking history and PCI are independent prognostic factors for OS of LS-SCLC.

Skeletal Muscle Depletion Predicts the Prognosis of Patients with Hepatocellular Carcinoma Treated with Radiation Therapy

Sarcopenia is gaining attention, being identified as a poor prognostic factor for various types of malignancies. Particularly, sarcopenia occurs frequently in cases of hepatocellular carcinoma (HCC) after treatment. However, the clinical significances of sarcopenia in patients underwent radiotherapy (RT) for HCC is not yet been identified. The purpose of this study is to evaluate the association between sarcopenia and survival in HCC patients underwent RT to the primary site. Between January 2009 and November 2016, a total number of 156 patients with stage I-IVB primary HCC underwent RT to the liver. Among these, 64 patients received RT with definitive aim, 43 patients with palliative aim, and 49 patients with salvage aim. Eighty-one patients were treated with concurrent chemotherapy (CTx), and 75 patients were treated with RT only. The median RT dose was 50.4 Gy (30 Gy-70 Gy). The cross-sectional area of muscle at the level of 3rd lumbar vertebra was measured using baseline CT images (L3 skeletal muscle index; L3-SMI). Sarcopenia was defined as a L3-SMI of less than 49 for men and less than 41 for women as proposed by Korean-specific cut off value. The sarcopenia was identified at two-time points; pre- and post-RT. Pre-RT sarcopenia was diagnosed with data from the simulation CT prior to RT, while post-RT sarcopenia was diagnosed with data from the follow-up CT taken within 3 months from the end of RT. Overall survival (OS) and progression-free survival (PFS) were estimated from the start of RT, and the prognostic factors associated with the survival were analyzed. Among a total of 156 patients, 3 patients were stage I, 15 patients were stage II, 48 patients were stage III, and 90 patients were stage IV, respectively. According to Korean-specific cut off value, 99 patients (63.5%) had pre-RT sarcopenia, while 109 patients (69.9%) had post-RT sarcopenia. Pre-RT sarcopenia group had higher percentage of patients with previous CTx (14.1 % vs 1.8 %), compared with those without pre-RT sarcopenia. At a median follow up 9.3 months, median OS were significantly differed according to the presence of pre-RT sarcopenia (7.1 vs. 15.3 months, p < 0.001) and post-RT sarcopenia (7.5 vs. 16.8 months, p < 0.001), while median PFS differed according to pre-RT sarcopenia with borderline significance (3.3 vs. 5.6 months, p = 0.051). In univariate analysis, total dose, Child-Pugh classification, cancer stage at time of RT, AFP level, Neutrophil-Lymphocyte ratio, Platelet-Lymphocyte ratio, pre-RT and post-RT sarcopenia have shown to be significant prognostic factors for OS. In multivariate analysis, total dose and pre-RT sarcopenia were identified as independent prognostic factors for OS. In our study, pre-RT sarcopenia was associated with a poor prognosis for HCC patients underwent RT to liver. This result suggests the possibility that the identification of sarcopenia in HCC patients before RT might enable the early intervention to maintain muscle mass and improve prognosis.

Metastatic acral lentiginous melanoma in a tertiary referral center in Switzerland: a systematic analysis

Acral lentiginous melanoma (ALM) is a unique histopathological subtype of melanoma with a poorer prognosis than other cutaneous melanomas. This study aims to evaluate the clinicopathological characteristics, metastatic pattern, prognostic factors, response to systemic therapy, and overall survival (OS) of ALM in a White population. This is a retrospective study of patients who were diagnosed and/or treated for ALM at the Department of Dermatology of the University Hospital Zurich, Switzerland, from January 2005 to December 2015. Overall, 172 patients with histologically confirmed ALM were included in the study. In univariate Cox regression, Breslow thickness (P<0.001), age (P=0.003), status of sentinel lymph node (P=0.005), and ulceration (P=0.008) were identified as significant prognostic factors for OS in ALM. In multivariate analysis, only Breslow thickness (P=0.0003) showed statistical significance. The median OS (mOS) was 155.7 months in the entire cohort (n=172) and 11.2 months for stage IV patients (n=36), irrespective of treatment. When first treatment was considered (n=35), mOS for stage IV patients was 8.9, 16.6, 21.7, and 3.7 months, for patients who had received chemotherapy (ChT) (n=17), immunotherapy (n=9), targeted therapy (TT) (n=3), and no therapy (n=6), respectively. The overall response rate was 44% (7/16 patients) to ChT, 100% to TT (3/3), and 25% to ipilimumab (2/8). In our study, Breslow thickness represents the best prognostic factor for OS. In stage IV ALM patients treated with either immunotherapy or TT, there is a trend for extended mOS compared with ChT.

Lipolysis-stimulated lipoprotein receptor overexpression is a novel predictor of poor clinical prognosis and a potential therapeutic target in gastric cancer.

The prognosis of patients with advanced gastric cancer (GC) remains poor despite the recent advances in molecular targeted therapies, and the search for biomarkers that can predict prognosis and additional new agents with acceptable toxicity profiles are needed. Lipolysis-stimulated lipoprotein receptor (LSR) is a lipoprotein receptor that binds to triglyceride-rich lipoproteins and related to some malignancies. Herein, we examined the association between LSR expression and the prognosis of patients with GC, and investigated the antitumor effect of a previously developed anti-human LSR monoclonal antibody (#1–25). We first performed immunohistochemical analysis of LSR protein expression in GC and normal tissues, and then examined its association with the prognosis of 110 patients with GC. LSR was overexpressed in most of primary GC and metastatic tumors, but not in normal tissues. Patients with strong LSR expression (N = 80, 72.7%) had significantly poorer overall survival (OS) than those with weak expression (P = 0.017). Multivariate analysis identified strong LSR (as well as pT) as independent and significant prognostic factors for OS. Next, we demonstrated that very low density lipoprotein (VLDL) treatment increases cell proliferation in LSR-expressing GC cell lines in vitro; LSR inhibition using #1–25 inhibited VLDL-induced proliferation by suppressing JAK/STAT and PI3K signaling. In vivo, we demonstrated a marked antitumor effect of #1–25 in 2 distinct GC cell line xenograft mice models. Our findings suggest that LSR plays a key functional role in GC development, and that this antigen can be therapeutically targeted to improve GC treatment.

Modeled Prognostic Subgroups for Survival and Treatment Outcomes in BRAF V600–Mutated Metastatic Melanoma

Prognostic models may provide insight into clinical trial results and inform the clinical management of patients with BRAF V600-mutated metastatic melanoma. To identify subgroups with distinct survival outcomes based on clinical and genomic characteristics and to assess survival in identified prognostic subgroups across cohorts treated with dacarbazine, vemurafenib, or cobimetinib plus vemurafenib. This retrospective and exploratory recursive partitioning analysis (RPA) modeled associations between prespecified covariates and survival outcomes using pooled data from the BRIM-2, BRIM-3, BRIM-7, and coBRIM studies. Dacarbazine, vemurafenib, or cobimetinib plus vemurafenib. Progression-free survival (PFS) and overall survival (OS), estimated using the Kaplan-Meier method. The RPA included 1365 patients (783 men; 57.4%). Of these, 1032 (75.6%) were older than 65 years; 310 received cobimetinib plus vemurafenib; 717, vemurafenib alone; and 338, dacarbazine. Median follow-up was 14.1 months (interquartile range, 6.3-28.3 months). In the RPA that included all patients, baseline lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group performance status (ECOG PS), presence or absence of liver metastases, and baseline sum of longest diameters of target lesions (SLDs) were significant prognostic factors for PFS: Median PFS was longest in patients with lower LDH (≤2 × upper limit of normal [ULN]), ECOG PS 0, and shorter SLD (≤44 mm) (11.1 months; 95% CI, 7.0-18.4 months), and shortest in those with elevated LDH (>2 × ULN) (3.5 months; 95% CI, 3.0-3.8 months). The subgroup with normal baseline LDH and no liver metastases had the longest median OS (22.7 months; 95% CI, 20.3-27.2 months). Similar PFS trends were observed when these prognostic subgroups were applied to the cobimetinib plus vemurafenib, vemurafenib alone, and dacarbazine cohorts. Baseline LDH, ECOG PS, and SLD were significant prognostic factors for OS: Median OS was longest in patients with normal LDH and shorter SLD (≤45 mm) (27.2 months; 95% CI, 22.1-32.1 months) and shortest in those with elevated LDH (>2 × ULN) (6.0 months; 95% CI, 5.3-6.8 months). Among patients in the most favorable subgroup (normal LDH and SLD ≤45 mm), 3-year OS rates were 53.3% (95% CI, 39.5%-67.1%) in the cobimetinib plus vemurafenib cohort, 35.6% (95% CI, 27.4%-43.8%) in the vemurafenib cohort, and 35.6% (95% CI, 24.8%-46.4%) in the dacarbazine cohort. Among patients with available gene expression data, RPA identified gene signature as a significant prognostic factor for PFS in those with normal LDH; 3-year PFS rates were 21.9%, (95% CI, 15.4%-28.4%) and 8.8% (95% CI, 3.6%-14.1%) in immune and cell cycle signature, respectively. The RPA for OS did not identify gene signature as a significant factor. Baseline LDH, ECOG PS, disease burden, and gene signature appear to be key determinants of survival outcomes in patients with BRAF V600-mutated metastatic melanoma treated with BRAF and/or MEK inhibitors. These results are consistent with survival benefits of cobimetinib plus vemurafenib over vemurafenib alone observed in the coBRIM study.

Liposarcoma: Clinico-pathological analysis, prognostic factors and survival in a series of 307 patients treated at a single institution

Background and objectivesLiposarcoma (LPS) is a malignant mesenchymal tumor and the most common soft tissue sarcoma. Four different subtypes are described: well differentiated (WD) LPS or atypical lipomatous tumor (ALT), dedifferentiated (DD) LPS, myxoid LPS, and pleomorphic LPS (PLS). The objective of the study was to investigate prognostic factors and clinical outcome of liposarcoma. MethodsWe retrospectively examined the clinico-pathological features of a series of 307 patients affected by Liposarcoma at a mean follow-up of 69 months (range 6–257). ALT/WD LPS were analyzed separately. The influence of site, size, type of presentation, grading, histotype and local recurrence on local and systemic control and survival was assessed. ResultsThe statistical analysis indicated that only surgical margins represented a significant prognostic factor for local recurrence in ALT/WD LPS (P = 0.0007) and other subtypes of LPS (P = 0.0055). In myxoid, PLS and DD LPS, significant prognostic factors for metastasis free survival (MFS) were surgical margins (P = 0.0009), size of the tumor (P = 0.0358), histology (P = 0.0117) and local recurrence (P = 0.0015). In multivariate analysis, surgical margins (0.0180), size (0.0432) and local recurrence (0.0288) correlated independently with MFS. Margins (P = 0.0315), local recurrence (P = 0.0482) and metastases (P < 0.0001) were prognostic factors for overall survival (OS). ConclusionMarginal surgery can be an accepted treatment for ALT/WD LPS. In other liposarcoma subtypes (Myxoid, DD, PLS) wide or radical surgery is recommended as the margins significantly influence local recurrence-free survival (LRFS), metastasis-free survival (MFS) and overall survival (OS). Local recurrence and metastases were significant prognostic factors for OS.

Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with de Novo Spinal Metastases Treated With Spine Stereotactic Body Radiation Therapy (SBRT)

We report mature outcomes for a cohort of patients with no prior radiation (de novo) to the spine treated with 24Gy in 2 daily fractions for metastases, which represents the same stereotactic body radiation therapy (SBRT) regimen under evaluation in the current Symptom Control-24 phase 3 randomized trial (NCT02512965). The cohort consisted of 279 de novo spinal metastases in 145 consecutive patients treated with 24Gy in 2 SBRT fractions, identified from a prospective single-institution database. The endpoints were overall survival (OS), imaging-based local failure (LF), and cumulative risk of vertebral compression fractures (VCF). The median follow-up per treated metastasis was 15.0months (range, 0.1-71.6). The 1-year and 2-year OS rates were 73.1% and 60.7%, respectively. Presence of epidural disease (P<.0001), lung (P=.0415), and renal cell (P<.0001) primary histologies and baseline diffuse metastases (P=.0034) were significant prognostic factors for OS. The 1-year and 2-year LF rates were 9.7% and 17.6%, respectively, and the median time to LF was 9.2month (range, 0.4-31.3months). Only the presence of epidural disease predicted for LF (P<.0001). The cumulative risk of VCF at 1 and 2years was 8.5% and 13.8%, respectively. Lytic (P=.0143) or mixed lytic/blastic (P=.0214) lesions, spinal malalignment (P=.0121), and the dose to 90% of the planning target volume (P=.0085) were significant predictors for VCF. Twenty-four Gray in 2 daily fractions is safe and effective in achieving high tumor control rates for de novo spinal metastases. These outcomes will serve as a benchmark for the ongoing Symptom Control-24 randomized trial comparing 24Gy in 2 SBRT fractions to 20Gy delivered in 5 daily conventional fractions.

Randomized, prospective, comparative study on the effects and safety of sorafenib vs. hepatic arterial infusion chemotherapy in patients with advanced hepatocellular carcinoma with portal vein tumor thrombosis.

Treatment responses of advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) remain unacceptably low and treatment modalities are limited. We compared the efficacy and safety of sorafenib and hepatic arterial infusion chemotherapy (HAIC). In this randomized, prospective, comparative study, data on 58 patients with advanced HCC with PVTT, with Child-Turcotte-Pugh (CTP) scores of 5-7, were collected from six university hospitals between January 2013 and October 2015. Twenty-nine patients were treated with sorafenib and twenty-nine with HAIC. The median overall survival (OS) and time to progression (TTP) were significantly longer in the HAIC group than in the sorafenib group (14.9 vs.7.2 months, p = 0.012 and 4.4 vs. 2.7 months, p = 0.010). The objective response (OR) rates were 27.6 and 3.4% in the HAIC and sorafenib groups, respectively (p = 0.001). In univariate analysis, sex, main portal vein invasion and treatment modality were significant prognostic factors of OS (p = 0.044, 0.040, 0.015), whereas cause of HCC, tumor number, tumor location and treatment modality were significant prognostic factors of TTP (p = 0.040, 0.002, 0.034, 0.014). In multivariate analysis, sex and treatment modality were significant prognostic factors of OS (p = 0.008, 0.005), whereas cause of HCC, tumor number, tumor location and treatment modality were significant prognostic factors of TTP (p = 0.038, 0.038, 0.015, 0.011). Major complications included hyperbilirubinemia (44.8%), AST elevation (34.5%), ascites (13.8%) and catheter-related complications (3.4%) in the HAIC group and hyperbilirubinemia (34.5%), hand-foot syndrome (31.0%) and AST elevation (27.6%) in the sorafenib group. For managing advanced HCC with PVTT, HAIC may be a valuable treatment modality.

Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme.

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA-IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA-IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA-IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA-IX expression (18 months) compared to patients overexpressing CA-IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA-IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA-IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross-total resection (HR, 1.956; P = 0.034). Our findings indicated that CA-IX may be a potential prognostic biomarker in the treatment of GBM.

Prognostic value of metabolic tumor volume and total lesion glycolysis in esophageal carcinoma patients treated with definitive chemoradiotherapy.

The aim of this study was to evaluate the prognostic importance metabolic tumor volume (MTV), total lesion glycolysis (TLG), and standardized uptake value (SUV) in patients with esophageal cancer treated with definitive chemoradiotherapy. Seventy-two esophageal cancer patients treated with definitive chemoradiotherapy [57 (79%) patients] or definitive radiotherapy [15 (21%) patients] were retrospectively analyzed. The regions equal to or greater than SUV of 2.5 were selected to delineate MTV and TLG was calculated by multiplying the mean SUV by the MTV of the primary lesions. The overall survival (OS) and disease-free survival (DFS) were evaluated for all patients and also patients with squamous cell carcinoma. The median survival time was 13.4 months (range: 1.8-119.3 months) for all patients. Maximum SUV, mean SUV, MTV, and TLG values were significantly higher in patients with extensive T-stage (T3-T4) compared with patients with T1-T2 disease. Patients with regional lymph node metastasis had significantly higher MTV and TLG values compared with patients with no lymph node metastasis. On multivariate analysis, MTV, TLG, presence of lymph node metastasis, and lack of concurrent chemotherapy were negative significant prognostic factors for OS and DFS for the entire cohort and for patients with squamous cell carcinoma esophageal cancer. Metabolic volumes (MTV and TLG), regional lymph node metastasis, and concurrent chemotherapy are major prognostic factors for DFS and OS in patients with esophageal carcinoma. In addition, MTV and TLG are important in predicting nodal metastasis, and together with metabolic volumes, SUV are associated significantly with local tumor invasion.

18F-FDOPA PET and MRI characteristics correlate with degree of malignancy and predict survival in treatment-naïve gliomas: a cross-sectional study.

To report the potential value of pre-operative 18F-FDOPA PET and anatomic MRI in diagnosis and prognosis of glioma patients. Forty-five patients with a pathological diagnosis of glioma with pre-operative 18F-FDOPA PET and anatomic MRI were retrospectively examined. The volume of contrast enhancement and T2 hyperintensity on MRI images along with the ratio of maximum 18F-FDOPA SUV in tumor to normal tissue (T/N SUVmax) were measured and used to predict tumor grade, molecular status, and overall survival (OS). A significant correlation was observed between WHO grade and: the volume of contrast enhancement (r = 0.67), volume of T2 hyperintensity (r = 0.42), and 18F-FDOPA uptake (r = 0.60) (P < 0.01 for each correlation). The volume of contrast enhancement and 18F-FDOPA T/N SUVmax were significantly higher in glioblastoma (WHO IV) compared with lower grade gliomas (WHO I-III), as well as for high-grade gliomas (WHO III-IV) compared with low-grade gliomas (WHO I-II). Receiver-operator characteristic (ROC) analyses confirmed the volume of contrast enhancement and 18F-FDOPA T/N SUVmax could each differentiate patient groups. No significant differences in 18F-FDOPA uptake were observed by IDH or MGMT status. Multivariable Cox regression suggested age (HR 1.16, P = 0.0001) and continuous measures of 18F-FDOPA PET T/N SUVmax (HR 4.43, P = 0.016) were significant prognostic factors for OS in WHO I-IV gliomas. Current findings suggest a potential role for the use of pre-operative 18F-FDOPA PET in suspected glioma. Increased 18F-FDOPA uptake may not only predict higher glioma grade, but also worse OS.

Factors influencing survival among patients with HER2-positive metastatic breast cancer treated with trastuzumab.

We have limited capability to predict survival among patients treated for metastatic HER2-positive breast cancer. Further research is warranted to identify significant prognostic and predictive factors. We identified all HER2-positive metastatic breast cancer patients receiving trastuzumab at the Sunnybrook Odette Cancer Centre (SOCC) from 1999 to 2013 through the Cancer Care Ontario (CCO) Registry (n=256) and selected patients with available pathology reports (n=154). A retrospective review was completed documenting clinical, pathologic, and laboratory characteristics at the time of first trastuzumab therapy and survival outcomes. Cox proportional hazards regression models were used to identify prognostic factors for overall survival (OS) (primary endpoint) and failure-free survival (FFS), adjusted for the known prognostic factors of the presence of CNS metastases and the presence of≥2 distant metastatic sites. A multivariable model identified older age [hazard ratio (HR) 1.18/decade, 95% confidence interval (CI) 1.02-1.37)], increased platelet-to-lymphocyte ratio (PLR) (HR 1.75/log-unit, 95% CI 1.25-2.46), increased serum alkaline phosphatase (ALP) (HR 1.87/log-unit, 95% CI 1.41-2.49), and ER positivity (HR 0.63, 95% CI 0.42-0.96) as significant prognostic factors for OS after adjusting for the presence of CNS metastasis (HR 3.19, 95% CI 1.59-6.38) and the presence of≥2 distant metastatic sites (HR 2.10, 95% CI 1.19-3.70). PLR (HR 1.54/log-unit, 95% CI 1.12-2.12) was the only prognostic factor associated with FFS after adjusting for CNS and≥2 distant metastatic sites. Older age, increased PLR, and ALP were identified as poor prognostic factors and ER positivity as a favorable prognostic factor for OS after adjusting for the presence of CNS metastasis and the presence of number of≥2 distant metastatic sites. Increased PLR was a poor prognostic factor for both OS and FFS, and warrants further investigation into its prognostic ability amongst patients with HER2-positive metastatic breast cancer.

The Modified Glasgow Prognostic Score in Patients with Gemcitabine-refractory Biliary Tract Cancer.

No standard second-line chemotherapy has been yet established for gemcitabine-refractory biliary tract cancer (BTC). We conducted multivariable Cox regression analysis to examine the prognostic factors for overall survival (OS) in patients who had received gemcitabine-based treatment. Forty-six patients received second-line chemotherapy. The median serum carbohydrate antigen 19-9 (CA 19-9) value was 487 U/ml. The modified Glasgow prognostic score (mGPS) was: 0 (n=24), 1 (n=10), or 2 (n=10). The second-line chemotherapy included: S-1 in 20 patients, gemcitabine-based in 20, and tyrosine kinase inhibitors in five. The median OS was 8.3 months, and the median progression-free survival was 3.0 months. Multivariate analysis identified serum CA 19-9 ≥500 U/ml, mGPS ≥1, and presence of liver metastasis as significant prognostic factors for OS. Second-line chemotherapy for gemcitabine-refractory BTC remains inadequate. Randomized trials with appropriate stratification criteria are required.

Leptomeningeal enhancement on preoperative brain MRI in patients with glioblastoma and its clinical impact.

Leptomeningeal enhancement (LME) on preoperative brain magnetic resonance imaging (MRI) does not always indicate leptomeningeal seeding (LMS). With Stupp's regimen, authors have treated glioblastoma patients with LME on preoperative brain MRI but here we tried to find the clinical impact of LME. From 2005 to 2015, 290 patients with glioblastoma have been treated with Stupp's regimen at Samsung Medical Center. Among these, 33 patients showed LME on preoperative brain MRI. We compared the clinical outcomes between the patients with or without LME on preoperative brain MRI and analyzed the clinical results according to changes of LME at following MRI. The median survival was 23 months, and 2-year overall survival (OS) and disease-free survival (DFS) rate was 46.3% and 19.6%, respectively. Prognostic factors for OS and DFS were Karnofsky performance status, extent of resection and adjuvant chemotherapy. MGMT promoter methylation status was a significant prognostic factor for DFS. However, LME was not a significant prognostic factor for OS (P=0.156) or DFS (P=0.193). Among the 33 patients with LME on preoperative MRI, 21 (63.6%) showed persistent LME at the next MRI. A statistically significant difference in 2-year survival was evident between patients with and without persistent LME (OS, 17.3% and 70.1%, respectively, P=0.044; DFS, 5.3% and 54.0%, respectively, P=0.006). The most common pattern of failure was local recurrence. However, patients with persistent LME displayed a higher incidence of LMS than patients without LME. LME on preoperative brain MRI did not affect the clinical results in glioblastoma patients treated with the Stupp's regimen. However, persistence of LME was associated with poor survival and high possibility of LMS. For these patients, the postoperative adjuvant treatment should focus on palliative aim or more aggressive treatment scheme should be followed to overcome the disastrous results.

Value of bone scan index for predicting overall survival among patients treated with radium-223 for bone metastatic castration-resistant prostate cancer.

216 Background: The objective of this study was to evaluate the bone scan index (BSI) as a prognostic biomarker for overall survival (OS) among patients treated with radium-223 (Ra-223) for bone metastatic castration-resistant prostate cancer (mCRPC). Methods: We retrospectively identified 42 men who had been treated with Ra-223 for bone metastatic CRPC between 2012 and 2017 and investigated correlations between the baseline clinical factors of age, time to CRPC, previous use of docetaxel, PSA, Gleason score, alkaline phosphatase (ALP), and BSI and OS by multivariate analysis using the Cox proportional hazard model. We also analyzed the correlations between OS and absolute BSI value or BSI change from baseline after 12 weeks of treatment. Continuous variables were classified as dichotomous. Results: The median age, PSA, and time to CRPC were 75.5 years, 42.8 ng/mL, and 11.2 months, respectively. The median observation period was 11.7 months. Twenty-five (59.5 %) of the 42 patients had completed six cycles of Ra-223 treatment. Twenty-two patients (52.4 %) had died, including 20 (47.6 %) of cancer, by the time of analysis. The median OS in the entire cohort was 20.7 months. Multivariate analysis also showed that only BSI (≥1.5 vs. &lt; 1.5, HR 3.72, 95% CI 1.17–11.79, p = 0.026) was significantly correlated with OS. The BSI had decreased in 16 (51.6%) of the 31 patients who had undergone bone scans after 12 weeks of treatment . Multivariate analysis showed that absolute BSI value after 12 weeks treatment was significantly correlated with OS (BSI (≥2.0 vs. &lt; 2.0%, HR 13.07, 95% CI 2.61–65.53, p = 0.002). No correlation was found between BSI change from baseline after 12 weeks and OS. Conclusions: According to multivariate analysis, both baseline BSI and PSA were significant prognostic factors for OS among men treated with Ra-223. Absolute BSI value after 12 weeks of Ra-223 treatment was also found to be an independent prognostic factor for OS.