Significant Prognostic Factors For Overall Survival Research Articles

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. < 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. < 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.

Outcomes and prognostic factors of selective lateral pelvic lymph node dissection with preoperative chemoradiotherapy for locally advanced rectal cancer.

The clinical significance of preoperative chemoradiotherapy (CRT) and lateral lymph node dissection (LLND) for locally advanced rectal cancer remains unclear. We have employed total mesorectal excision and selective LLND following preoperative CRT for patients with locally advanced rectal cancer. The validity of our strategy was evaluated. A total of 45 patients with locally advanced rectal cancer who underwent curative surgery after CRT from November 2005 to September 2016 were retrospectively analyzed. LLND was performed only for the patients with lateral lymph nodes suspected to have metastasis based on the pretreatment images. Rates of 5-year overall survival (OS) and 5-year relapse-free survival (RFS) were 85.7 and 61.8%, respectively. Univariate and multivariate analyses detected only histological response (grades 2 and 3 vs. grade 1) as a significant prognostic factor for OS and local recurrence. ypN and ypStage were significant factors for RFS by univariate analysis, while no significant factor was detected by multivariate analysis. There was no significant factor for distant recurrence. In good responders (grades 2 and 3), the local recurrence rate was 0% (P = 0.006, vs. grade 1), while distant recurrence developed in 4 of 20 cases (20%, P = 0.615, vs. grade 1). There was no local recurrence in LLND (-) group regardless the histological response. Although selective LLND with preoperative CRT seems effective and valid for good responders, new treatment strategy is necessary for poor responders. Therefore, development of reliable biomarkers for histological response to CRT is an urgent need.

Survival in patients with submandibular gland carcinoma — Results of a multi-institutional retrospective study

ObjectiveClinical studies demonstrating the prognostic factors in submandibular gland carcinoma are limited because the tumor is relatively rare. The aim of this study was to identify clinical outcomes and prognostic factors in submandibular gland carcinoma. MethodsThe study included 65 patients with submandibular gland carcinoma who underwent initial surgical treatment at the Kyoto University and its affiliated hospitals. ResultsThe 3-year overall survival (OS), disease specific survival, locoregional control (LRC), and no distant metastasis (NDM) rates were 74.2%, 74.2%, 90.0%, and 64.8%, respectively. In the current follow-up study, 16 patients died of the disease, 5 patients were alive with recurrence, 43 patients were alive without disease, and 1 patient died of unrelated disease without recurrence. All patients who died of the disease had developed distant metastasis. Based on univariate analysis, tumor grade (high grade) and lymph node metastases (≥N2) were significant prognostic factors for OS and LRC. It also revealed tumor grade (high grade), T classification (≥T3), and lymph node metastases (≥N2) were significant for distant metastasis. Multivariate analysis showed the following significant prognostic factors: lymph node metastases (≥N2) for OS, LRC, and NDM, and high tumor grade for NDM. ConclusionOur study suggested death of submandibular gland carcinoma occurred mainly due to distant metastasis. The significant predictors of distant metastasis were lymph node metastases (≥N2) and tumor grade (high grade).

Novel prognostic scoring system for diffuse large B-cell lymphoma.

The objective of the present study was to evaluate the prognostic values of platelet count (PLT) and platelet to lymphocyte ratio (PLR) in diffuse large B-cell lymphoma (DLBCL), creating a novel prognostic scoring system. A total of 309 patients with newly diagnosed DLBCL were retrospectively analyzed. Receiver operating characteristic analysis was used to determine the optimal threshold values for PLT and PLR, which were 250×109/l and 170, respectively. The patients with PLT ≥250×109/l and PLR ≥170 experienced significantly decreased overall survival (OS) (P<0.001) and progression-free survival (PFS) times (P=0.003, P<0.001) In multivariate analysis, PLR was a significant prognostic factor for OS (P<0.001) and PFS (P=0.003) time, whereas PLT was not a risk factor for PFS or OS time. According to the results of Cox regression analysis, a novel prognostic scoring system was created that combined PLR and β2-microglobulin level with International Prognostic Index value or age-adjusted International Prognostic Index value and the patients were divided into three groups: i) Low-risk patients with a PLR <170, International Prognostic Index (IPI) <2 scores or age-adjusted International Prognostic Index (aaIPI)=0 and normal β2m; ii) high-risk patients with a PLR ≥170, IPI ≥4 or aaIPI=3 and high level of β2m; and iii) intermediate-risk patients. The novel score predicted 5-year OS rates of 86.4, 54.1 and 21.1% in the low-, intermediate- and high-risk groups, respectively (P<0.001). This novel prognostic scoring system may aid the evaluation of patient prognosis and guide treatment.

Retrospective observational study of salvage line ramucirumab monotherapy (RAM) for patients (pts) with unresectable advanced gastric cancer (AGC) which was refractory to fluoropyrimidine and taxanes.

129 Background: RAM showed a survival benefit over best supportive care in second-line treatment after failure of fluoropyrimidine-containing chemotherapy for pts with advanced gastric or gastro-esophageal junction adenocarcinoma (AGC). In clinical practice, RAM is used for some pts who have disease refractory to fluoropyrimidine and taxanes in salvage line setting. Methods: We retrospectively evaluated efficacy and safety of RAM in salvage lines between June 2015 and April 2017 for AGC at four Japanese institutions. All pts received 2 or more prior regimens containing fluoropyrimidine and taxanes, but not ramucirumab. We also explored prognostic factors for progression free survival (PFS) and overall survival (OS). Results: Fifty-one pts were collected. Pts' characteristics were as follows; median age: 67 (range 39-84) years; ECOG performance status ≤ 1: 43 (84%) pts; HER2 positive: 17 (33%) pts; number of metastatic sites ≥ 2: 29 (57%); number of prior therapies 2/3/4/5: 7(14%)/25(49%)/12(24%)/7(14%) pts. Median PFS and OS were 1.9 (95% confidence interval [CI]: 1.6-2.2) and 5.1 (95% CI: 4.1-6.8) months, respectively. Twelve-week PFS rate was 25.5%. Objective response rate in 43 pts who had measurable disease was 2%. Disease control rate was 35%. Grade 3 adverse events (AEs) occurred in 7 (13%) pts such as anemia in 2 (4%), fatigue in 1 (2%), hypertension in 2 (4%), proteinuria in 2 (4%), intestinal bleeding in 1 (2%), and others in 2 (4%) pts. No grade 4 AEs and treatment related deaths were observed. Although multivariate analyses suggested that absence of primary tumor and neutrophil lymphocyte ratio &lt; 2.5 at baseline were associated with better PFS, while statistically significant prognostic factors for OS were not identified in this study. Conclusions: Salvage line RAM showed acceptable toxicities and comparable efficacy with those reported in previous studies of second-line setting. It is suggested that RAM could be considered for salvage line treatment after fluoropyrimidine and taxanes containing regimens.

Relationship between ethnicity and overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib (S).

248 Background: The SHARP and Asia Pacific (AP) trials showed that S improves OS compared to placebo in advanced HCC. However, OS was worse in the AP trial which included predominantly Asian patients. It is unclear if ethnicity, or perhaps Hepatitis B (HBV) infection, is a poor prognostic factor for these patients. The purpose of this study was to determine whether ethnicity affects OS in patients with advanced HCC being treated with S. Methods: All patients treated with S for HCC in Alberta, Canada from 01/2008 to 07/2016 were included. Patient demographics and clinical/pathological variables were retrospectively collected. Patients were dichotomized by ethnicity as either East Asian or not according to a validated list of surnames. Survival outcomes were assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox-proportional hazard model was constructed with ethnicity and relevant clinical/pathological characteristics to assess their impact on survival. Results: A total of 175 patients were included. Mean age was 64 years. 78% were men, 28% were East Asian, and 79% were Child-Pugh A at initiation of S. The most common etiologies of underlying liver disease were Hepatitis C (HCV) (31%), HBV (29%) and alcohol (21%). 42% had distant metastatic disease. The majority of patients had an ECOG performance status of 0 (26%) or 1 (64%). Median OS was 9.0 months in Asians and 9.5 months in non-Asians (p = 0.68). On multivariate analysis, ethnicity (HR 0.76, 95% CI 0.39 – 1.32, p = 0.33) was not a significant prognostic factor for OS. However, lack of distant metastases (HR 0.57 95% CI 0.40 - 0.82, p &lt; 0.01), initial AFP &lt; 400 (HR 0.54 95%CI 0.38 - 0.78, p &lt; 0.01) and 3+ localized treatments (HR 0.60 95% CI 0.39 - 0.92, p = 0.02) were associated with better OS. Further, HBV was associated with inferior OS when compared to HCV (HR 2.12, 95% CI 1.08 - 4.17, p = 0.03). Conclusions: When treated with S in one Canadian province, ethnicity does not appear to be a prognostic factor for OS. However, HCV infection, lack of distant metastases, initial AFP &lt; 400, and 3+ previous localized treatments were significant prognosticators of OS. We are validating these findings in a larger multi-centre Canadian dataset.

Supratentorial extraventricular ependymomas: A retrospective study focused on long-term outcomes and prognostic factors

ObjectiveSupratentorial extraventricular ependymomas are relatively rare. Long-term outcomes and prognostic factor for this rare tumor have not been well established. The purpose of this study was to demonstrateprogression-freesurvival(PFS),overallsurvival(OS), and prognostic factors of such tumor. Patients and methodsFifty-five patients with supratentorial extraventricular ependymomas from our hospital were included in this study. Epidemiological characteristics, clinical features, treatment,long-term outcomes, and prognostic factors for PFS and OS were reviewed retrospectively. ResultsThe patients consisted of 30 males and 25 females with mean age of 30.0 ± 23.6 years (range, 1–74 years). Twenty-nine tumors were located in the right hemisphere, and 26 in the left side. The 2 most common tumor locations were the frontal (n = 19; 35%) and parietal lobe (n = 11; 20%). All patients underwent surgical resection. Gross-total resection (GTR) was achieved in 42 cases (76%) and subtotal resection (STR) was performed in 13 patients (24%). According to the WHO classification system, 38 tumors (69%) were Grade III (anaplastic ependymoma), and 17 (31%) were Grade II (ependymoma). Three-,5-, and 10 year PFS rates were 60%, 49%, and 36%, respectively. Three-,5-, and 10 year OS rates were 79%, 64%, and 49%, respectively. EOR and tumor grade were identified as prognostic factors for PFS and OS on univariate analysis, multivariate analysis, and Kaplan-Meierlog-rank testing. Subtotal resection (STR) predicted a worse PFS (HR = 4.808; 95%, 1.942–11.905; P = .001) and OS (HR = 5.650; 95%, 2.114–15.152; P = .001). WHO Grade III tumors also had worse PFS (HR = 3.922; 95%, 1.429–18.182; P = .012) and OS (HR = 6.329; 95%, 1.328–30.303; P = 0.021). For patients with tumor recurrence, reoperation was significant prognostic factors for OS (HR = 2.091; 95%, 0.939–4.654; p = .000). Age, sex, tumor side, and postoperativeradiotherapy were not prognostic factors for PFS and OS. ConclusionsMost supratentorial extraventricular ependymomas are WHO grade III tumors. STRandWHO Grade III pathology predicted worse PFS and OS. Gross-total resection remains the optimal treatment for patients with supratentorial extraventricular ependymoma. Reoperation should be considered first in cases of recurrence. The role of postoperative radiotherapy as an adjuvant treatment for supratentorial extraventricular ependymoma needs further investigation.

Prognostic Factors in Patients With Spinal Chordoma: An Integrative Analysis of 682 Patients.

The low incidence of spinal chordoma precludes a prospective study of prognostic factors with a large patient cohort. To perform a comprehensive integrative analysis on the prognostic factors, treatment, and outcomes of patients with spinal chordoma using data from 2 institutions and the literature. Appropriate studies were identified per search criteria. The local database was retrospectively searched to include a similar patient cohort. Overall, 108 studies from the literature and 30 patients from our local institution were identified, resulting in a total of 682 patients. The median age was 57 years old and 35.2% were female. The median follow-up was 46 months (range: 1-408). The median progression-free survival (PFS) and overall survival (OS) were 72 months and 115 months, respectively. Significant prognostic factors for PFS on multivariate analysis included age (pediatric vs adult, hazard ratio [HR]: 2.00-14.36), tumor location (mobile spine vs sacral spine, HR: 0.31-0.87), pathology (differentiated vs classic, HR: 2.48-10.90),and chemotherapy (HR:1.11-3.85). Significant prognostic factors for OS on multivariate analysis included age (geriatric vs adult, HR: 1.52-3.45 and pediatric vs adult, HR: 1.73-9.36), bladder or bowel dysfunction (HR: 1.27-5.43), pathology (dedifferentiated vs classic, HR: 2.38-11.09), recurrence or progression (HR: 1.72-4.48), and metastases (HR: 1.11-2.47). In patients with spinal chordoma, young age, location in sacral spine, dedifferentiated pathology, and chemotherapy were negative predictors of PFS, while young and old age, bladder or bowel dysfunction at presentation, dedifferentiated pathology, recurrence or progression, and metastases portended a worse OS.

Prognostic value of volumetric FDG PET/CT parameters in patients with oral tongue squamous cell carcinoma who were treated by superselective intra-arterial chemoradiotherapy.

This study aimed to evaluate the predictive and prognostic value of FDG PET/CT-based volumetric parameters in patients with oral tongue squamous cell carcinoma (OTSCC) treated by superselective intra-arterial chemoradiotherapy (IA-CRT). We conducted a retrospective study including 33 patients with biopsy-proven OTSCC between May 2007 and February 2016. All of the patients were treated by IA-CRT. Pretreatment SUVmax and metabolic tumor volume (MTV) of the primary tumor were measured. The SUV thresholds of 2.5 and 5.0 were used. Progression-free survival (PFS) and overall survival (OS) were chosen as endpoints to evaluate prognosis. Univariate and multivariate analyses were performed to assess the potential independent effect of FDG PET/CT parameters. The median follow-up for surviving patients was 40.7months (range 6.0-107.5months). In univariate and multivariate analyses, SUVmax and MTV (5.0) were independent prognostic factors for PFS. In univariate analysis, SUVmax failed to predict OS. MTV (5.0) was a significant prognostic factor for OS, but multivariate analysis failed to show statistical independence because it could not exclude the possibility of an artifact due to N stage. FDG PET/CT-based volumetric parameters may be significant prognostic markers for survival of patients with OTSCC who are treated by IA-CRT.

Prognostic group stratification and nomogram for predicting overall survival in patients who received radiotherapy for abdominal lymph node metastasis from hepatocellular carcinoma: a multi-institutional retrospective study (KROG 15-02).

ObjectiveTo develop a prognostic model for overall survival (OS) in hepatocellular carcinoma (HCC) patients receiving radiotherapy (RT) to metastatic abdominal lymph nodes (LNs).Materials and MethodsTwo hundred twenty-eight patients treated with RT to metastatic abdominal LNs were retrospectively reviewed.ResultsMedian OS in all patients was 11.1 months. LN responders had significantly higher median OS than non-responders (14.2 months vs. 7.5 months, p<0.05). On multivariate analysis, Child-Pugh classification, status of intrahepatic tumor, presence of distant metastasis, number and location of metastatic LNs, serum level of alpha fetoprotein (AFP), and the LN response to RT were significant prognostic factors for OS (p < 0.05 each). Based on the results of multivariate analysis, prognostic group stratification according to the number of pre-treatment risk factors was a significant predictor of OS, and median OS in patients with ≥ 4, 3, 2, 1, and 0 risk factors were 2.9, 5.5, 10.3, 13.6, and 27.8 months, respectively (p<0.05). A nomogram was formulated by integrating the different prognostic contribution of each factor, and it showed good accuracy for predicting 2-year OS with a concordance index of 0.72.ConclusionPrognostic group stratification and nomogram could be useful prognostic and therapeutic indicators in selecting treatment strategies.

Clinical and Prognostic Significance of Pathological and Inflammatory Markers in Mucinous Rectal Cancer Patients Receiving Neoadjuvant Chemoradiotherapy and Curative Surgery

BackgroundThe aim of this study was to investigate the clinical and prognostic significance of pathological and inflammatory marker in mucinous rectal cancer patients receiving neoadjuvant chemoradiotherapy and curative surgery.Material/MethodsWe retrospectively evaluated the patient records of mucinous rectal cancer patients receiving neoadjuvant chemoradiotherapy and curative surgery at Liaoning Cancer Hospital and Institute from January 2006 to December 2013. The relationship between overall survival (OS) and clinicopathologic variables, pretreatment neutrophil-to-lymphocyte ratio (NLR), pretreatment platelet-to-lymphocyte ratio (PLR), pretreatment lymphocyte-to-monocyte ratio (LMR), and other biomarkers were analyzed by using Kaplan-Meier analysis and log-rank testing. Subsequently a Cox proportional hazard model was used to calculate hazard ratios for the risk of death.ResultsA total of 100 mucinous rectal cancer patients were included for analysis during the study period. The median age at presentation was 60.5 years (range, 26–81 years). The median overall survival (OS) for the whole group was 94 months. On univariate analysis, time interval from CCRT to operation (HR 0.37, p=0.03), lymphovascular invasion (HR 3.23, p=0.009), pretreatment NLR (HR 3.87, p=0.012), and LMR (HR 0.31, p=0.002) were significant prognostic factors for OS. In a multivariate analysis, pretreatment LMR was found to be an independent prognostic factor for overall survival (HR, 0.43; 95%CI, 0.18 to 1.00, p=0.045).ConclusionsPretreatment lymphocyte-to-monocyte ratio is a useful prognostic marker of OS in patients with mucinous rectal carcinoma treated with neoadjuvant chemoradiotherapy and curative surgery.

Impact of Synchronous Multiple Primary Malignant Tumors on Newly Diagnosed Hematological Malignancies.

Hematological malignancies are occasionally observed with synchronous multiple primary malignant tumors (sMPMTs) at diagnosis. We aimed to clarify the impact of sMPMTs on newly diagnosed hematological malignancies and determine the optimal treatment strategies. We analyzed the outcomes of 649 patients with hematological malignancies, including 19 patients with sMPMTs (2.9%), and compared the outcomes between patients with and without sMPMTs. The overall survival (OS) and disease-free survival (DFS) rates for patients with sMPMTs were 77% and 70%, respectively, at 2 years; these rates were not statistically different from those for patients without sMPMTs (P= .17 and P= .64, respectively). Multivariate analysis showed that the presence of sMPMTs was not a significant prognostic factor for OS, DFS, or relapse (hazard ratio [HR] 1.48, 95% confidence interval [CI] 0.65-3.38, P= .35; HR 0.97, 95% CI 0.46-2.10, P= .97; and HR 0.79, 95% CI 0.29-2.14, P= .65). In patients with sMPMTs, the order of treatment was not a significant prognostic factor. However, discontinuation of treatment was a marginally favorable factor and might reflect a selection bias. The presence of sMPMTs was not a significant risk factor for patients with newly diagnosed hematological malignancies. It is important to provide adequate treatment for both hematological malignancies and solid tumors at the physician's discretion.

Prognostic Value of the Age-Adjusted Charlson Comorbidity Index (ACCI) on Short- and Long-Term Outcome in Patients with Advanced Primary Epithelial Ovarian Cancer.

We evaluated the prognostic impact of the age-adjusted Charlson Comorbidity Index (ACCI) on both postoperative morbidity and overall survival (OS) in patients with advanced epithelial ovarian cancer (EOC) treated at a tertiary gynecologic cancer center. Exploratory analysis of our prospectively documented tumor registry was performed. Data of all consecutive patients with stage IIIB-IV ovarian cancer who underwent primary cytoreductive surgery (PDS) from January 2000 to June 2016 were analyzed. Patients were divided into three groups, based on their ACCI: low (0-1), intermediate (2-3), and high (≥4), and postoperative surgical complications were graded according to the Clavien-Dindo classification (CDC). The Fisher's exact test, log-rank test, and Cox regression models were used to investigate the predictive value of the ACCI on postoperative complications and OS. Overall, 793 consecutive patients were identified; 328 (41.4%) patients were categorized as low ACCI, 342 (43.1%) as intermediate ACCI, and 123 (15.5%) as high ACCI. A high ACCI was significantly associated with severe postoperative complications (CDC 3-5; odds ratio 3.27, 95% confidence interval 1.97-5.43, p<0.001). Median OS for patients with a low, intermediate, or high ACCI was 50, 40, and 23months, respectively (p<0.001), and the ACCI remained a significant prognostic factor for OS in multivariate analysis (p=0.001). The same impact was observed in a sensitivity analysis including only those patients with complete tumor resection. The ACCI is associated with perioperative morbidity in patients undergoing PDS for EOC, and also has a prognostic impact on OS. The potential role of the ACCI as a selection criteria for different therapy strategies is currently under investigation in the ongoing, prospective, multicenter AGO-OVAR 19 trial.

Combined prognostic effect of PD-L1 expression and immunoscore in microsatellite-unstable advanced gastric cancers.

BackgroundThe aim of this study was to evaluate how programmed death-ligand-1 (PD-L1) expression is linked to the immunoscore in the context of the tumor microenvironment and to assess the differential prognostic value of PD-L1 expression according to the immunoscore in 153 patients with microsatellite instability-high (MSI-H) advanced gastric cancer (GC).ResultsWe found that T-PD-L1 (+) and I-PD-L1 (+) were significantly associated with a high immunoscore. The integrated PD-L1 expression of tumor and immune cells was not significantly correlated with the overall survival (OS) of patients. However, a combined survival analysis of PD-L1 expression and immunoscore revealed four distinct subgroups with a statistically significant difference in OS. That is, the PD-L1 (+)/immunoscoreLow group showed the worst and the PD-L1 (+)/immunoscoreHigh group showed the best prognosis. Furthermore, a multivariate analysis revealed that the combined status of PD-L1 expression and immunoscore was an independent and significant prognostic factor for OS in patients with MSI-H GC.Materials and MethodsThe immunoscore was quantified by the number of high-density areas of CD3+ and CD8+ tumor infiltrating lymphocytes both in the tumor regions and compartments (i.e., epithelial and stromal compartments of the tumor center and the invasive front), the scores of which range from I0 to I8. By using immunohistochemistry, the expression of PD-L1 was also analyzed in tumor cells (T-PD-L1) and immune cells (I-PD-L1) using four different cut-off values (1%, 5%, 10% and 50%).ConclusionsOur study revealed that PD-L1 expression is associated with the corresponding immunoscore and that the immunoscore can be a relevant marker for the determination of the prognostic role of PD-L1 expression in MSI-H GCs.

Adjuvant radiochemotherapy in locally advanced gastric cancer : Treatment results and analysis of possible prognostic factors.

The aim of this study was to report the clinical outcome and toxicity of radiochemotherapy in locally advanced gastric cancer (LAGC) patients treated according to the Intergroup 116 trial protocol in our institution. We retrospectively reviewed 105 patients with LAGC treated with radical surgery and adjuvant radiochemotherapy. We analyzed overall survival (OS), disease-free survival (DFS), locoregional failure-free survival (LFS), prognostic factors and toxicity. The mean follow-up was 96.48months. The majority of tumors were T3-T4 (75%) and 86.6% had nodal metastases. The OS, DFS and LFS rates to 3 years were 53.48%, 52.75% and 81.65%, respectively and to 5 years 40%, 46.73% and 76.77% respectively. The univariate analysis showed that Nstage< N2, TN stage< IIIA, R0 resection and N‑ratio< 3 were statistically significant prognostic factors for OS and DFS, Tstage< T4 for OS and N‑ratio< 3 for LFS. The group with D2 lymphadenectomy had worse LFS than the D1 group (65.2% vs 88.1%, respectively, p= 0.039) probably due to asignificant difference in the proportion node positive patients in the D2 group (94% vs. 78%; p= 0.027). In the multivariate analysis, only R0 resection was statistically significant factor for improved OS (p= 0.018). Acute gradeIII-IV gastrointestinal and hematologic toxicity rates were 8.5% and 15.2%, respectively and 89.5% completed treatment as planned. Our results are consistent with those of the Intergroup-0116 trial for LAGC in terms of survival. This regimen is well tolerated and with acceptable toxicity. An R0 resection was an independent prognostic factor for improved OS.

Clinical outcomes of salvage chemoradiotherapy for locally recurrent biliary tract cancer.

The purpose of this study was to investigate the clinical outcomes and prognostic factors of concurrent chemoradiotherapy (CCRT) for locally recurrent biliary tract cancer (BTC) after curative surgical resection. We performed a retrospective cohort study of patients with locally recurrent BTC treated with CCRT between October 2004 and December 2013. The study included and analyzed 42 patients with a history of curative-intent surgical resection of confirmed adenocarcinoma originating from the biliary tract. The median time to recurrence after surgery was 16.1 months (range, 4.5-77.8 months). Median follow-up after CCRT was 26.9 months (range, 5.2-81.9) with no grade 3 or higher gastrointestinal toxicities. Analysis of the first site of failure showed local progression (LP) developed in 20 patients (47.6%); among these, 16 (38.1%) had isolated LP. The median values were 15.8 months (range, 1.7-81.7) for LP-free survival (LPFS), 10.6 months (range, 1.7 - 81.7) for progression-free survival (PFS) and 41.2 months (range, 5.2-81.9) for overall survival (OS). Multivariate analysis showed that the level of pre-CCRT carbohydrate antigen (CA) 19-9 and the chemotherapy regimen were significant prognostic factors for LPFS and PFS; pT stage was the only significant prognostic factor for OS. CCRT for locally recurrent BTC showed promising outcomes as a salvage modality, but LP was still frequent. The pre-CCRT CA 19-9 level and the chemotherapy regimen were prognostic factors for LPFS and PFS.

Human papillomavirus infection increases the chemoradiation response of esophageal squamous cell carcinoma based on P53 mutation

Background and purposeA retrospective study was carried out to analyze multiple prognostic predictors, including human papillomavirus (HPV) infection for chemoradiation treatment of esophageal squamous cell carcinoma (ESCC). Materials and methodsDNA extracted from a total of 192 patients treated with chemoradiation for locally advanced ESCC was examined to determine HPV status by polymerase chain reaction (PCR) and P53 gene mutation by genetic sequencing. The relationships between the chemoradiation response (CRR) and overall survival (OS) rate with HPV status and P53 gene mutation were analyzed. ResultsThirty-two of the 108 patients with P53 mutated tumors were stained positive for HPV, while thirty-five of the 84 P53 wild-type tumors were HPV positive. P53 mutation and HPV infection were two independent events (p=0.083, Kappa=0.083). HPV infection increased the CRR (p=0.017) and 3-year OS (p=0.047) compared with the HPV negative group. This difference was more significant in the P53 mutation subgroup (CRR p=0.019; OS p=0.025). However, HPV infection led to no difference in the P53 wild-type subgroup (CRR p=0.802; OS p=0.468). The P53 mutation status was an independent prognostic factor (CRR p=0.034; OS p<0.001). Age was another significant prognostic factor for OS (p=0.001). ConclusionsDepending on P53 mutation status, HPV infection can contribute to a higher tumor response and better prognosis of ESCC treated with chemoradiation therapy.