Five-year Recurrence-free Survival Research Articles

Pancreas sparing duodenectomy versus pancreaticodudoenectomy for duodenal carcinoma: a comparison study

Background: Pancreas-sparing duodenectomy (PSD) may be an alternative to pancreaticoduodenectomy (PD) for duodenal cancers located distant from the ampulla. PSD avoids the potential complications of a pancreaticoenteric anastomosis, but the long-term outcomes are unknown. Methods: Patients who underwent surgical resection of duodenal cancer were identified from a prospectively maintained database. Clinical and pathological data were collected, and long-term cancer-related outcomes were analyzed. Results: 19 patients underwent PSD and 60 PD between January 1993 and March 2014. Morbidity (p=0.196), 90-day mortality (p=0.379) and length of stay (p=0.137) were similar in both groups. However, there were more anastomotic leaks in the PD group (33% versus. 5%; p=0.017). Lymph node yield (p<0.001) was significantly lower after PSD. There was no significant difference in five-year overall (p=0.943), disease-specific (p=0.781) or recurrence-free (p=0.695) survival rates. No significant difference in the lymph node ratio (LNR) between the groups. Conclusions: PSD avoids the risks of a pancreatic anastomosis associated with PD. Despite a significantly lower lymph node harvest, similar survival outcomes can be achieved with PSD in patients with duodenal carcinoma not involving D 2 .

Prognostic Value of Prostaglandin-endoperoxide Synthase 2 Polymorphisms in Prostate Cancer Recurrence after Radical Prostatectomy

Backgroud: Increasing evidence suggests the involvement of chronic inflammation in the progression of prostate cancer, and prostaglandin-endoperoxide synthase 2 (PTGS2), also known as cyclooxygenase-2, catalyzes the rate-limiting steps of the pathway. We hypothesized that genetic variants of PTGS2 can influence the outcome of prostate cancer patients.Methods: We genotyped five haplotype-tagging single-nucleotide polymorphisms (SNPs) to detect common genetic variations across the PTGS2 region in 458 prostate cancer patients treated with radical prostatectomy.Results: One SNP, rs4648302, was associated with disease recurrence. Five-year recurrence-free survival rate increased according to the number of variant alleles inherited (55.6%, 70.7%, and 100.0% for patients with different genotypes; P = 0.037), and the effect was maintained in multivariable analysis. Public dataset analyses also suggested that PTGS2 expression was correlated with prostate cancer prognosis.Conclusion: Our results indicated that PTGS2 could be a potential prognostic marker to improve the prediction of disease recurrence in prostate cancer patients.

Transarterial Chemoembolization Prior to Liver Transplantation in Patients with Hepatocellular Carcinoma.

Transarterial chemoembolization (TACE) induces ischemic tumor necrosis, which is intensified by regional chemotherapy. By reducing the active tumor tissue, it can be assumed that patients on the waiting list for liver transplantation may benefit from this locoregional treatment. The aim of this study was to assess the relevance of TACE in hepatocellular carcinoma (HCC) patients before liver transplantation. A retrospective analysis was performed on data of 229 patients who were transplanted for HCC. A group of 75 patients were treated with TACE prior to liver transplantation. Tumor necrosis related to pretransplantation locoregional treatment was assessed in an explanted liver and classified into extensive (51-100%), moderate (26-50%) and limited (<25%) grades. Five-year recurrence-free survival was estimated using the Kaplan-Meier method and compared using the log-rank test. In total, 143 HCC lesions were treated with TACE. Extensive necrosis was found in 63 (44.0%) tumors. Moderate and limited necrosis were observed in 42 (29.4%) and 38 (26.6%) tumors, respectively. In 36 (58.1%) explanted livers, every tumor was classified as extensively necrotic. The 5-year recurrence-free survival was estimated as 81.6% in the group not treated with TACE prior to liver transplantation (TACE-) and as 73.1% in the TACE+ group (p=0.169). Among patients not fulfilling the Milan criteria, 5-year recurrence-free survival was 63.1% in TACE- and 65.1% in TACE+ (p=0.656). In conclusion, TACE prior to liver transplantation is effective in inducing tumor necrosis. However, evidence of benefits in long-term results after liver transplantation requires further confirmation.

Concomitant Administration of Proton Pump Inhibitors and Capecitabine is Associated With Increased Recurrence Risk in Early Stage Colorectal Cancer Patients

BackgroundCapecitabine is used to treat colorectal (CRC) cancer. TRIO-013, a study examining capecitabine/oxaliplatin ± lapatinib in metastatic gastro-esophageal cancer did not show increases in overall survival (OS) with lapatinib. An analysis showed concurrent proton pump inhibitor (PPI) usage negatively impacted recurrence-free survival (RFS). We retrospectively studied PPI effects on capecitabine efficacy in early stage CRC and how capecitabine adjustments impacted RFS. MethodsEarly stage CRC patients taking monotherapy capecitabine treated from 2008 to 2012 were reviewed for demographics, medications, toxicities, and patient outcomes. ResultsOf 298 identified patients, 25.8% (n = 77) received concurrent PPIs. Five-year RFS was 74% versus 83% (hazard ratio [HR], 1.89; 95% confidence interval [CI], 1.07-3.35; P = .03) in PPI versus non-PPI patients respectively. OS was 81% versus 78%, respectively (HR, 1.13; 95% CI, 0.60-2.14; P = .7). After accounting for gender, stage, age, and performance status, PPI patients tended toward decreased RFS (HR, 1.65; 95% CI, 0.93-2.94; P = .09). Capecitabine dose modifications affected outcomes. Five-year RFS was 84% in the control group, 100% in the treatment-delay group (P = .99), 67% in the dose reduction group (HR, 2.46; 95% CI, 1.23-4.93; P = .01), and 64% in the discontinuation group (HR, 2.27; 95% CI, 0.93-5.53; P = .07). Five-year OS was significantly less in the discontinuation group than control group (59% vs. 82%; HR, 3.27; 95% CI, 1.44-7.45; P = .005). ConclusionsPPIs appear to impact RFS; this may be due to PPIs preventing capecitabine tablet dissolution and absorption. Patients with dose reductions or who stopped treatment had worse outcomes than patients who continued with treatment at starting doses.

Dermal melanoma: A report on prognosis, outcomes, and the utility of sentinel lymph node biopsy.

Historically dermal melanoma (DM) has been labeled as either stage IIIB (in-transit) or stage IV (M1a) disease. We sought to investigate the natural history of DM and the utility and prognostic significance of sentinel lymph node biopsy (SLNB). Patients with DM undergoing SLNB at a single center from 1998 to 2009 were identified. Eighty-three patients met criteria, 10 (12%) patients had a positive SLNB. Of those, 5 (50%) recurred (all with distant disease). Twenty-one (29%) of the 73 SLNB negative patients recurred and of those, 15 (71%) developed distant metastases, whereas 6 (29%) developed local or regional recurrence, including two false-negative regional nodal recurrences. No in-transit recurrences were recorded. Five-year recurrence-free and disease-specific survival was significantly better for patients with a negative SLNB versus positive SLNB (56.8% vs. 22.2% P = 0.02, 81.1% vs. 61.0%, P = 0.05, respectively). SLNB has prognostic significance for RFS and DSS, and should be utilized in the management of DM based on a >10% yield and low false-negative rate. Our data demonstrate patients with DM do not recur in an in-transit fashion, which along with the survival outcomes suggest the behavior of DM is consistent with primary cutaneous melanoma of similar thickness rather than an isolated in-transit or distant dermal metastasis from a regressed cutaneous primary.

Association of neutrophil-to-lymphocyte ratio with the prognosis in patients with renal cell carcinoma

Objective To explore prognostic factors of renal cell carcinoma and investigate the association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of renal cell carcinoma (RCC) in patients who received nephrectomy treatment. Methods We retrospectively reviewed the records of 1325 patients with renal cell carcinoma who underwent nephrectomy between January, 2008 and December, 2012. We retrospectively analyzed the clinicopathologic characteristics of patients. The optimal cutoff value for NLR was determined using receiver operating characteristic curve (ROC) analysis. We defined them as high NLR group when NLR ≥ 2.7 and low NLR group when NLR<2.7. Overall survival (OS) and recurrence free survival (RFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate models were used to analyze the association of NLR with clinicopathologic outcomes. Results By the end of the study, 1220 cases were followed up. The follow-up rate was 92.1%. Mean follow-up was 40 months (range 2 months to 87 months). The three-year and five-year overall survival rate were 91.3% and 86.9%, respectively. Meanwhile the three-year and five-year recurrence free survival rate were 88.2% and 85.8%, respectively. 2.7 was selected as the optimal cutoff value to differentiate between low NLR and high NLR. A NLR ≥2.7 was significantly associated with worse 5-year overall survival and worse 5-year recurrence free survival than a NLR 65, presentation mode with symptom, higher tumor stage, higher Fuhrman grade, histologic subtype, neutrophil count≥4.5, lymphocyte count<1.7, NLR ≥2.7 significantly correlated with poor OS on univariate analysis. Multivariate analysis revealed that higher tumor stage, preoperative NLR ≥2.7 at diagnosis were poor independent prognostic factors for OS of renal cell carcinoma. Conclusion High NLR was independent poor predictor of renal cell carcinoma. Key words: Carcinoma, renal cell; Neutrophil-to-lymphocyte ratio; Prognosis; Survival rate

Video-assisted thoracoscopic surgery versus open thymectomy for thymoma: a systematic review.

Video-assisted thoracoscopic surgery (VATS) thymectomy is an increasingly utilized alternative to traditional open approaches for the resection of thymomas. Recent studies have suggested comparable survival and oncological efficacy as well as reduced perioperative morbidity when using the VATS approach. This current systematic review thus aimed to critically evaluate existing evidence for the efficacy and safety of VATS versus open (transsternal or transthoracic) thymectomy for thymomas. Six electronic databases were searched from their date of inception to April 2015. Relevant studies were identified using specific eligibility criteria and data were extracted and analyzed based on predefined primary and secondary endpoints. Fourteen comparative observational studies with a total of 1,061 patients were obtained for qualitative assessment, data extraction and analysis. Five-year overall survival and 10-year recurrence-free survival was similar or higher in patients undergoing VATS compared to open thymectomy. On average, the VATS group also demonstrated reduced intraoperative blood loss (131.8 vs. 340.5 mL), shorter hospital stays (7.0 vs. 9.8 days), and lower rates of postoperative pneumonia (1.9% vs. 4.1%). The mean rate of conversion from VATS to open thymectomy was relatively low (3.1%), while 30-day mortality remained low in both the VATS and open groups (0 vs. 0.3%). The current evidence suggests that VATS thymectomy for thymoma has at least equal if not superior oncological efficacy and survival outcomes, as well as reduced perioperative complications, compared to open surgery. Further adequately powered studies and future randomized trials are required to confirm these findings.

Laparoscopic Versus Open Surgery for Gastric Gastrointestinal Stromal Tumors: What Is the Impact on Postoperative Outcome and Oncologic Results?

The aim of the study was to compare the postoperative and oncologic outcomes of laparoscopic versus open surgery for gastric gastrointestinal stromal tumors (gGISTs). The feasibility of the laparoscopic approach for gGIST resection has been demonstrated; however, its impact on outcomes, particularly its oncologic safety for tumors greater than 5 cm, remains unknown. Among 1413 patients treated for a GIST in 61 European centers between 2001 and 2013, patients who underwent primary resection for a gGIST smaller than 20 cm (N = 666), by either laparoscopy (group L, n = 282) or open surgery (group O, n = 384), were compared. Multivariable analyses and propensity score matching were used to compensate for differences in baseline characteristics. In-hospital mortality and morbidity rates in groups L and O were 0.4% versus 2.1% (P = 0.086) and 11.3% vs 19.5% (P = 0.004), respectively. Laparoscopic resection was independently protective against in-hospital morbidity (odds ratio 0.54, P = 0.014). The rate of R0 resection was 95.7% in group L and 92.7% in group O (P = 0.103). After 1:1 propensity score matching (n = 224), the groups were comparable according to age, sex, tumor location and size, mitotic index, American Society of Anesthesiology score, and the extent of surgical resection. After adjustment for BMI, overall morbidity (10.3% vs 19.6%; P = 0.005), surgical morbidity (4.9% vs 9.8%; P = 0.048), and medical morbidity (6.2% vs 13.4%; P = 0.01) were significantly lower in group L. Five-year recurrence-free survival was significantly better in group L (91.7% vs 85.2%; P = 0.011). In tumors greater than 5 cm, in-hospital morbidity and 5-year recurrence-free survival were similar between the groups (P = 0.255 and P = 0.423, respectively). Laparoscopic resection for gGISTs is associated with favorable short-term outcomes without compromising oncologic results.

Outcomes for patients with papillary thyroid cancer who do not undergo prophylactic central neck dissection.

The role of prophylactic central neck dissection (CND) in the management of papillary thyroid cancer (PTC) is controversial. This report describes outcomes of an observational approach in patients without clinical evidence of nodal disease in PTC. All patients who had surgery between 1986 and 2010 without CND for PTC were identified. All patients had careful clinical assessment of the central neck during preoperative and perioperative evaluation, with any suspicious nodal tissue excised for analysis. The cohort included patients in whom lymph nodes had been removed, but no patient had undergone a formal neck dissection. Recurrence-free survival (RFS), central neck RFS and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Of 1798 patients, 397 (22.1 per cent) were men, 1088 (60.5 per cent) were aged 45 years or more, and 539 (30.0 per cent) had pT3 or pT4 disease. Some 742 patients (41.3 per cent) received adjuvant treatment with radioactive iodine. At a median follow-up of 46 months the 5-year DSS rate was 100 per cent. Five-year RFS and central neck RFS rates were 96.6 and 99.1 per cent respectively. Observation of the central neck is safe and should be recommended for all patients with PTC considered before and during surgery to be free of central neck metastasis.

Five-year biochemical recurrence-free and overall survival following high-dose-rate brachytherapy with additional external beam or radical prostatectomy in patients with clinically localized prostate cancer

IntroductionHigh-dose-rate brachytherapy (HDR-BT) with external-beam radiation therapy and radical prostatectomy (RP) are common treatment options for clinically localized prostate cancer. The aim was to describe risk factors for biochemical recurrence (BCR) and death, as well as BCR rates and overall survival (OS) rates in both treatment groups. Patients and methodsOverall, 5,619 patients with localized prostate cancer underwent either RP (n = 5,200) or HDR-BT (n = 419) between 1999 and 2009. Median follow-up time was 72.4 months. Kaplan-Meier analyses and multivariable Cox regression analyses were performed for the overall cohort and for a propensity score–matched cohort to predict BCR and OS rates. Within the matched cohort, stratified analyses were repeated for HDR-BT alone (n = 206) and HDR-BT plus androgen deprivation therapy (ADT) (n = 213). Sensitivity analyses were performed to adjust for prostate-specific antigen rebound. ResultsThe 5-year BCR-free survival rates were 82.1% vs. 80.3% (P<0.01) for RP and HDR-BT, respectively. Corresponding 5-year OS rates were 97.1% vs. 92.4% (P<0.01). In the propensity score–matched cohort, 5-year BCR-free survival rates were 80.3% vs. 77.1%; P = 0.06 and 5-year OS rates were 95.7% vs. 92.4%; P = 0.5. In multivariable models, the overall HDR-BT exerted no significant effect on BCR, and the same results were recorded in the matched cohort. In stratified analyses, HDR-BT alone vs. RP increased BCR risk (1.45; P<0.01); conversely, HDR-BT plus ADT vs. RP decreased BCR risk (hazard ratio = 0.66; P = 0.02). ConclusionsFirst, RP offers equivalent oncological control without the need for concurrent hormone therapy and its morbidity. Second, patients who have RP avoid ADT (2%) and the need for salvage and adjuvant external-beam radiation therapy is low at 11% and 3%, respectively.

Patients with High Grade Bladder Cancer, and Tumor-Free 3 and 6-Month Cystoscopy after bacillus Calmette-Guérin have a Good Prognosis without Further Maintenance bacillus Calmette-Guérin

IntroductionThe benefit of 3 years of maintenance bacillus Calmette-Guérin has been questioned. The outcome is reported for bacillus Calmette-Guérin treated patients who had negative 3 and 6-month cystoscopy results and were subsequently not treated with maintenance bacillus Calmette-Guérin. MethodsA retrospective, population based study of patients with high grade nonmuscle invasive bladder cancer treated with bacillus Calmette-Guérin was performed. Patients were included in analysis who had tumor-free cystoscopy findings 3 and 6 months after the start of treatment. No patient was treated with maintenance bacillus Calmette-Guérin after the 6-month cystoscopy. The Kaplan-Meier estimated 5-year survival rates were calculated. ResultsThree and 6-month cystoscopy revealed no tumor in 196 patients with a median age of 72 years. Of the patients 84% had carcinoma in situ or multiple and/or recurrent high grade tumors. Five-year recurrence-free, progression-free and disease specific survival was 69%, 95% and 98%, respectively. Median followup in 119 patients who were alive at the last contact was 79 months. Recurrence developed in 62 of 196 patients (32%), disease stage progressed to at least T2 in 13 (7%) and 7 (3%) died of bladder cancer. ConclusionsPatients without maintenance bacillus Calmette-Guérin after tumor-free 3 and 6-month cystoscopy have a low rate of progression and bladder cancer death. An alternative to 1 to 3 years of bacillus Calmette-Guérin maintenance may be no maintenance after the second tumor-free cystoscopy with re-treatment with bacillus Calmette-Guérin in case of recurrence.

Partial Cystectomy for Primary Bladder Tumors in Contemporary Patients with Diverse Tumor Locations

IntroductionPartial cystectomy use has historically been limited by stringent selection criteria. We compared outcomes following partial cystectomy at our institution with those in other contemporary series. Also, we specifically characterized outcomes in patients with tumors in bladder locations traditionally considered unamenable to partial cystectomy. MethodsPatients who underwent partial cystectomy for primary bladder cancer from 1990 to 2012 were identified from our database. Clinical and pathological data were reviewed. Survival analyses were performed using Kaplan-Meier methods. Cox regression was done to identify factors associated with survival and recurrence. ResultsA total of 55 patients were included in analysis. Five-year overall, disease specific and recurrence-free survival was 70.3%, 77.0% and 39.4%, respectively. When controlling for clinical and pathological covariates, lymphovascular invasion predicted decreased recurrence-free survival (HR 10.6, p = 0.025). Perioperative morbidity and mortality rates were 4% and 5%, respectively. In 8 patients (15%) trigone tumors required ureteral reimplantation. Two of the 8 patients (25%) experienced complications, including hydronephrosis and bladder neck contracture, which were treated conservatively. Cancer recurred in 2 of the 8 patients (25%) and both were treated successfully. None of the 8 patients died of bladder cancer. ConclusionsPatients treated with partial cystectomy for primary bladder cancer had satisfactory cancer control and favorable perioperative morbidity consistent with other contemporary reports. Patients with tumors in the bladder trigone, historically considered poor candidates for partial cystectomy, also had good oncologic outcomes without significant complications related to reimplantation. Our data further support partial cystectomy in select patients with bladder cancer.

Statin Use and Serum Lipid Levels Are Associated With Survival Outcomes After Surgery for Renal Cell Carcinoma

To evaluate the association of statin use and preoperative serum lipid parameters with oncologic outcomes following surgery for renal cell carcinoma. A total of 850 patients who underwent surgery for localized renal cell carcinoma at our institution from 2000 to 2012 were included. Use of statins, preoperative serum lipid profile, and comprehensive clinicopathologic features were retrospectively recorded. Kaplan-Meier analysis and multivariate Cox proportional hazards model were employed to compare survival outcomes. There were 342 statin users and 508 non-users. Median follow-up was 25.0 months. Statin users were older, had greater body mass index, and had worse performance status than non-users. Tumor pathologic characteristics were balanced between groups. Five-year recurrence free survival (RFS) was 77.9% for non-users compared with 87.6% for statin users (P = .004). After adjustment for clinicopathologic variables, statin use was independently associated with improved RFS (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.33-0.86, P = .011) and overall survival (HR 0.45, 95%CI 0.28-0.71, P = .001). In patients with available serum lipid parameters (n = 193), 5-year RFS was 83.8% for patients with triglycerides <250 mg/dL compared with 33.3% for those with triglycerides >250 mg/dL (P <.0001). Elevated serum triglycerides (>250 mg/dL) was independently associated with worse RFS (HR 2.69, 95%CI 1.22-5.93, P = .015) on multivariate analysis. Statin use was independently associated with improved survival, whereas elevated serum triglyceride levels correlated with worse oncologic outcomes in this cohort. These findings warrant validation in prospective studies.

A Report on the Clinical Outcome after High-Dose Rate (HDR) Brachytherapy as Monotherapy in Early Prostate Cancer.

Background: To report the clinical outcome after a single implant, high dose rate (HDR) brachytherapy in early prostate cancer.Materials and Methods: All clinically localized prostate cancer patients who underwent high-dose rate (HDR) brachytherapy as monotherapy (no external beam radiotherapy) from February 2006 to September 2011 were analyzed prospectively. Acute and chronic toxicity were assessed as per Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03. Biochemical recurrence was analyzed using the Kaplan Meir method. A log-rank analysis was done to compare the factors affecting the outcome.Results: Forty-four patients with organ-confined prostate cancer opted for HDR brachytherapy between February 2006 to September 2011 with a median follow-up of 68 months The five-year biochemical recurrence-free survival (bRFS) rate was 91%. Late Grade 2 genitourinary (GU) toxicity was observed in 9% of patients. The predictors of late Grade 2 GU toxicity were urethra V125 ≥ 0.2 cc (urethral volume receiving ≥ 125% of the prescribed dose) and PTV 150 ≥ 35% ( planning target volume receiving ≥ 150% of the prescribed dose) with p-value = 0.001 and 0.002, respectively. Erectile function was preserved in 72% of the patients who had Grade 0-1 erectile dysfunction before brachytherapy.Conclusion: HDR brachytherapy in early prostate cancer results in high local control rates with minimal side-effects.

Recurrence in patients with stage I colorectal cancer.

Outcomes of patients with stage I colorectal cancer submitted to surgery with curative intent have not been thoroughly explored in contemporary series. All patients with colon or rectal adenocarcinoma who underwent resection from the St John of God Hospital (1996-2013) and BioGrid (1991-2013) databases were identified. Patients submitted to local excision, polypectomies or neoadjuvant treatment were excluded. Outcomes included recurrence (combined local and systemic), recurrence-free and overall survival, and survival after recurrence. A total of 1193 patients with stage I disease were included. Median age was 67 (interquartile range 59-75) and median follow-up was 3.2 years (interquartile range 1.4-5.8). Five-year recurrence rate was 7.1% (95% confidence interval (CI) 5.4-9.4%; 5.0% for colon and 11.1% for rectal cancer). Rectal location was an independent predictor of recurrence (hazard ratio (HR) 1.97, 95% CI 1.09-3.55; P = 0.024). Lymphovascular invasion was an independent predictor of recurrence only in patients with rectal cancer (HR 3.0, 95% CI 1.2-7.6; P = 0.018). Five-year recurrence-free survival was 83.2% (95% CI 80.3-85.4%). Age (HR 1.05, 95% CI 1.03-1.07; P < 0.001), elective surgery (HR 0.41, 95% CI 0.21-0.80; P = 0.011) and the American Society of Anesthesiologists (ASA) score (HR 3.08, 95% CI 1.51-6.31; P < 0.001) were independently associated with recurrence-free survival. Median survival after recurrence was 41 months. Resection of recurrence was attempted in 39% of patients. Patients with stage I colorectal cancers still have a clinically significant risk of recurrence. Rectal location is independently associated with higher recurrence. Age, elective surgery and ASA are independently associated with recurrence-free survival. A significant proportion of patients with recurrence underwent further resection.

Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma.

The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC). Patients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed. Among 84 patients with ACC, 29 (34.%) had NLR > 5 while 32 (40.5%) had PLR > 190. NLR and PLR were associated with larger tumors (NLR > 5: ≤ 5 cm, 0% vs. >5 cm, 39.7%; PLR > 190: ≤ 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR > 5: other organ resected 48.8% vs. not resected 20.9%; PLR > 190: other organ resected 25.0% vs. not resected 56.4%)(all P < 0.05). Five-year RFS was associated with an elevated NLR (NLR ≤ 5, 14.2% vs. NLR> 5, 10.5%) and PLR (PLR ≤ 190: 19.4% vs. PLR > 190: 5.2%) (both P < 0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P < 0.05). Immune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC.

Prognostic Factors for Local, Loco-regional and Systemic Recurrence in Early-stage Breast Cancer.

Aim: The risk of recurrence in breast cancer depends on factors such as treatment but also on the intrinsic subtype. We analyzed the risk factors for local, loco-regional and systemic recurrence, evaluated the differences and analyzed the risk of recurrence for different molecular subtypes. Material and Methods: A total of 3054 breast cancer patients who underwent surgery followed by adjuvant treatment at HSK hospital or Essen Mitte Hospital between 1998 and 2011 were analyzed. Based on immunohistochemical parameters, cancers were divided into the following subgroups: luminal A, luminal B (HER2-), luminal B (HER2+), HER2+ and TNBC (triple negative breast cancer). Results: 67 % of tumors were classified as luminal A, 13 % as luminal B (HER2-), 6 % as luminal B (HER2+), 3 % as HER2+ and 11 % as TNBC. After a median follow-up time of 6.6 years there were 100 local (3.3 %), 32 loco-regional (1 %) and 248 distant recurrences (8 %). Five-year recurrence-free survival for the overall patient collective was 92 %. On multivariate analysis, positive nodal status, TNBC subtype and absence of radiation therapy were found to be independent risk factors for all forms of recurrence. Age < 50 years, tumor size, luminal B (HER2-) subtype and breast-conserving therapy were additional risk factors for local recurrence. Compared to the luminal A subtype, the risk of systemic recurrence was higher for all other subtypes; additional risk factors for systemic recurrence were lymphatic invasion, absence of systemic therapy and mastectomy. Conclusion: Overall, the risk of local and loco-regional recurrence was low. In addition to nodal status, subgroup classification was found to be an important factor affecting the risk of recurrence.

Role of radiotherapy in treating patients with primary malignant mediastinal non-seminomatous germ cell tumor: A 21-year experience at a single institution.

BackgroundThe aim of this study was to investigate the clinical characteristics and outcomes of patients with primary malignant mediastinal non-seminomatous germ cell tumor (MMNSGCT) by comparing the efficacies of different treatment modalities.MethodsThe charts of 62 consecutive patients with MMNSGCT between 1990 and 2010 were reviewed. Analyses included Kaplan-Meier survival and Cox multivariate regression.ResultsThere was sufficient data of 61 patients for inclusion in the study. The median age was 25 years. At diagnosis, 35 patients had tumors located in the mediastinum, 26 had lung and/or distant metastases. At a median follow-up of 47.2 months, 32 patients had died and 43 had developed progressive disease. The one, three, and five-year overall survival (OS) and progression-free survival (PFS) rates were 72.1%, 50.8%, 49.2% and 47.5%, 32.8%, 32.8%, respectively. Patients who received radiotherapy in the primary treatment regimen showed improved five-year OS (68.2% vs. 38.5%, P = 0.043), PFS (45.5% vs. 20.5%, P = 0.023), and local recurrence-free survival (LRFS) (77.3% vs. 38.5%, P = 0.003) compared with those who did not receive radiotherapy. Multivariate analysis revealed that radiotherapy was an independent prognostic factor of five-year OS (hazard ratio [HR] 0.39, P = 0.037), PFS (HR 0.42, P = 0.017), and LRFS (HR 0.31, P = 0.019).ConclusionRadiotherapy in a chemotherapy-based treatment regimen could significantly reduce local recurrence and improve survival of MMNGCT patients.

Primary Surgery vs Chemoradiation Treatment of Advanced-Stage Hypopharyngeal Squamous Cell Carcinoma.

There is no consensus whether primary surgery followed by either adjuvant radiotherapy (RT) or adjuvant chemoradiation (CRT) or definitive CRT should be the standard treatment approach to advanced-stage hypopharyngeal squamous cell carcinoma (HP SCC). To determine survival outcomes for patients with advanced-stage HP SCC treated at a single institution with either primary surgery plus RT or CRT or definitive CRT. We conducted a retrospective analysis of prospectively collected medical records in an institutional database for patients with HP SCC newly diagnosed between January 1999 and April 2013. Overall survival (OS) and recurrence-free survival (RFS) were calculated and compared between treatment groups using the Kaplan-Meier method, with multivariate Cox regression analysis used to control for demographic and clinicopathologic features. We identified 166 consecutively treated patients, 90 of whom did not meet study criteria. Of the 76 included patients, 48 (63%) had undergone definitive CRT, and 28 (37%) had undergone primary surgery with adjuvant RT or CRT. The groups were well balanced by age, smoking history, and alcohol use. Five-year OS and RFS for patients treated surgically were 66.3% and 53.6%, respectively; for patients treated with definitive CRT, OS and RFS were 41.3% and 34.5%, respectively. Multivariate Cox regression analysis showed that surgical management was associated with clinically improved OS (hazard ratio [HR], 4.78; 95% CI, 0.91-25.03; P = .06) and RFS (HR, 2.97; 95% CI, 0.76-11.53; P = .12), although the difference was not statistically significant. Patients with advanced-stage HP SCC treated surgically with adjuvant RT or CRT showed a trend toward clinically improved OS and RFS compared with patients treated with definitive CRT. However, the difference was not statistically significant, and further investigation with larger controlled trials using modern approaches should be undertaken to optimize the initial management of advanced-stage HP SCC.

Refining prognosis and identifying targetable pathways for high-risk endometrial cancer; a TransPORTEC initiative

This study aimed to investigate whether molecular analysis can be used to refine risk assessment, direct adjuvant therapy, and identify actionable alterations in high-risk endometrial cancer. TransPORTEC, an international consortium related to the PORTEC3 trial, was established for translational research in high-risk endometrial cancer. In this explorative study, routine molecular analyses were used to detect prognostic subgroups: p53 immunohistochemistry, microsatellite instability and POLE proofreading mutation. Furthermore, DNA was analyzed for hotspot mutations in 13 additional genes (BRAF, CDKNA2, CTNNB1, FBXW7, FGFR2, FGFR3, FOXL2, HRAS, KRAS, NRAS, PIK3CA, PPP2R1A, and PTEN) and protein expression of ER, PR, PTEN, and ARID1a was analyzed. Rates of distant metastasis, recurrence-free, and overall survival were calculated using the Kaplan–Meier method and log-rank test. In total, samples of 116 high-risk endometrial cancer patients were included: 86 endometrioid; 12 serous; and 18 clear cell. For endometrioid, serous, and clear cell cancers, 5-year recurrence-free survival rates were 68%, 27%, and 50% (P=0.014) and distant metastasis rates 23%, 64%, and 50% (P=0.001), respectively. Four prognostic subgroups were identified: (1) a group of p53-mutant tumors; (2) microsatellite instable tumors; (3) POLE proofreading-mutant tumors; and (4) a group with no specific molecular profile (NSMP). In group 3 (POLE-mutant; n=14) and group 2 (microsatellite instable; n=19) patients, no distant metastasis occurred, compared with 50% distant metastasis rate in group 1 (p53-mutant; n=36) and 39% in group 4 (NSMP; P<0.001). Five-year recurrence-free survival was 93% and 95% for group 3 (POLE-mutant) and group 2 (microsatellite instable) vs 42% (group 1, p53-mutant) and 52% (group 4, NSMP; P<0.001). Targetable FBXW7 and FGFR2 mutations (6%), alterations in the PI3K-AKT pathway (60%) and hormone receptor positivity (45%) were frequently found. In conclusion, molecular analysis of high-risk endometrial cancer identifies four distinct prognostic subgroups, with potential therapeutic implications. High frequencies of targetable alterations were identified and may serve as targets for individualized treatment.