Predictive Factors For Overall Survival Research Articles

Is lymph-node ratio better prognostic factor for overall survival than number of positive lymph node for stage III pancreatic cancer?

Background: Pancreatic cancer is the fourth most fatal cancer in men and women worldwide. It is estimate that pancreatic cancer have tendency to become the second most common cause of cancer-related death by 2030. Aim of this study was to define is LNR better predictive factor for overall survival (OS) than number of positive lymph node.

Pretreatment Lung Immune Prognostic Index Is a Prognostic Marker of Chemotherapy and Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor.

BackgroundLung immune prognostic index (LIPI) was recently developed on the basis of the combination of baseline derived neutrophil to lymphocyte ratio (dNLR) and lactate dehydrogenase (LDH). This index was demonstrated as a specific biomarker of immune checkpoint inhibitors for non-small cell lung cancer (NSCLC). We aimed to show that LIPI may be a useful biomarker of cytotoxic chemotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for NSCLC.MethodsWe retrospectively collected 175 wild-type EGFR adenocarcinomas, 131 NSCLCs harboring mutant EGFR and 110 squamous cell carcinomas. All patients initiated first-line cytotoxic chemotherapy or EGFR-TKI monotherapy between July 2007 and August 2017 at our hospital. These patients were divided into good, intermediate and poor LIPI groups. We compared their overall survival (OS) and progression-free survival (PFS). Multivariate analyses detected prognostic and predictive factors of OS and PFS.ResultsThe good LIPI group survived longer than the intermediate and poor LIPI groups in wild-type EGFR adenocarcinoma (good, intermediate and poor LIPI groups: median 19.6, 11.5 and 3.3 months, P < 0.01, respectively) and mutant EGFR NSCLC (45.4, 25.6 and 15.7 months, P < 0.01). The PFS of good LIPI group was significantly longer that those of the other two groups in mutant EGFR NSCLC (16.6, 12.6 and 8.3 months, P < 0.01). The intermediate group (hazard ratio (HR) 1.49, 95% confidential interval (CI) 1.03 - 2.15, P = 0.04) of wild-type EGFR adenocarcinoma, intermediate (HR 2.30, 95% CI 1.33 - 3.99, P < 0.01) and poor (HR 2.76, 95% CI 1.03 - 7.42, P = 0.04) groups of mutant EGFR NSCLC were independent prognostic factors of poor OS. The intermediate (HR 1.57, 95% CI 1.01 - 2.44, P = 0.04) and poor (HR 2.63, 95% CI 1.14 - 6.07, P = 0.02) groups were significant prognostic factors of PFS of mutant EGFR NSCLC.ConclusionsLIPI was an independent prognostic factor of chemotherapy for adenocarcinoma with wild-type EGFR and of EGFR-TKI for NSCLC harboring mutant EGFR. Thus, LIPI was not a specific biomarker for ICI therapy, but a useful biomarker for chemotherapy and EGFR-TKI therapy in specific subsets of NSCLC.

A reappraisal of bioprosthetic structural valve degeneration after aortic valve replacement: Mode, outcome and effect of treatment

Structural valve degeneration (SVD) remains the main complication of aortic bioprosthesis. The study aimed to evaluate SVD mode, outcome and effect of treatment. Patients with presumed aortic SVD by echocardiography in our institution between January 2010 and December 2016 were included. All-cause mortality, cardiovascular morbidity, and effect of treatment were assessed. After exclusion of 4 patients with others causes of increased gradients, 220 patients were analyzed (78 ± 9 years, 52% men). Regurgitant SVD ( n = 94, 43%) occurred later than stenotic ( n = 126, 57%) SVD (9.2 ± 3.7 vs. 7.9 ± 3.0 years; P = 0.003). Patients with a regurgitant SVD were more symptomatic, had a larger bioprosthesis, and were more often referred to invasive management. Exclusive medical care (Med) was retained in 67 patients, redo-surgery in 89 and VinV in 64. Macroscopic examination of explanted bioprostheses ( n = 71) demonstrated severe calcifications in 56.3%, mainly in stenotic SVD (71 vs. 42%, P = 0.02), and leaflet tear in 28%. Overall survival at 35 months was significantly associated with the type of management (VinV: 85.3 ± 4.9%, redo-surgery 86.7 ± 3.8%, Med 60.1 ± 7.7%, P < 0.0001). In multivariable analysis, predictive factors of overall survival were bioprosthesis type, Nt proBNP level (HR = 1.52 [95% CI: 1.17–1.97], P = 0.002), transvalvular maximal velocity, and invasive management (Redo-surgery: HR = 0.35 [95% CI: 0.15–0.81], P = 0.014; VinV: HR = 0.32 [95% CI: 0.13–0.77], P = 0.011) as compared to Med. Structural valve degeneration remains a matter of concern. Regurgitant SVD occurs later than stenotic SVD which is characterized by a more severe calcification process. Redo-surgery and VinV are associated with a better outcome, independently of failure mode, and should be considered in most SVD patients. Although VinV was proposed to older and higher-risk patients, its effect on overall survival was comparable to redo-surgery in multivariable analysis.

Tubular and mucinous breast cancer: results of a cohort of 917 patients.

To analyze axillary lymph node involvement (ALNI) rate and survival for mucinous (MC) and tubular (TC) breast carcinomas considered being of very good prognosis and for which an axillary surgical exploration could be questioned. Our multicentric cohort consisted of 21,135 patients with clinically node-negative invasive breast cancer, without neoadjuvant therapy, between 1999 and 2013 in 10 French centers. ALNI rate and survival were analyzed according to patient and tumor characteristics. Our cohort consisted of 672 TC and 245 MC. Patients were older and tumor size greater for MC and pathologic factors were more pejorative. The rate of mastectomies and adjuvant chemotherapy was higher in the MC group. Axillary lymph node status was determined by SLNB alone in 71.2% of patients. ALNI rates were 17.9% and 18% for TC and MC, respectively. ALNI rate was lesser for MC (OR 0.503, p = 0.024) and greater in case of lympho-vascular invasion (OR 5.0, p < 0.0001) and for tumors >10 mm (OR 2.17, p = 0.042). Median follow-up was 58 months. The 5- and 7-year overall survival rates were 97.1% and 95% for TC, respectively; 92.3% and 91.2% for MC ( p = 0.043); 5- and 7-year disease-free survival rates were 97.9% and 97.2% versus 95.2 and 93.6% ( p = 0.041). Lympho-vascular invasion was the only predictive factor for overall survival (hazard ratio [HR] = 2.70)' grade 2 (HR = 10) and HR-negative (HR = 4.9) were the two predictive factors for disease-free survival. This study confirms the need for an axillary exploration for these tumors even for a tumor size <10 mm and a favorable prognosis.

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.

Clinical behaviours and prognoses of high- and low-risk parotid malignancies based on histology.

To report 5-year survival in patients with primary parotid malignant tumours and assess the impact of various factors on survival or local control among diverse histologic groups. A total of 65 patients with primary parotid malignant tumours who had surgery between 2003 and 2014 were identified. Demographic characteristics including age, T stage, N stage and clinical or pathological performance were analysed. According to risk stratification (based on pathology), 65 primary parotid malignant tumours were divided into high-risk (23, 35.38%) and low-risk (35, 53.85%) groups. Overall survival (OS) and disease-free survival (DFS) were recorded by the Kaplan-Meier methods. The 5-year overall survival rate for primary parotid malignant tumours was 70.9%. Patients older than 60years with fixed mass, pain, facial-nerve palsy and high-grade N stage had adverse OS and DFS. Upon multivariable analysis, facial-nerve palsy (HR 24.59; 95% CI 2.338-178.446; P = 0.002) was the only independent predictive factor for OS. Patients with high-risk parotid malignant types were more likely to have tumour pain, facial-nerve palsy (Chi-square test: < 0.0001 and 0.02), lymphatic metastasis and local/regional recurrence (Chi-square test: 0.008 and 0.012). Compared with low-risk parotid carcinoma, tumours with high-risk histological features tend to need aggressive surgical extirpation, neck dissection and postoperative radiotherapy.

Geriatric Impairments and Low Muscle Mass Are Associated with Treatment Discontinuation and Overall Survival in Newly Diagnosed Non-Transplant Eligible Multiple Myeloma Patients (nte-NDMM) Treated with Dose-Adjusted Melphalan-Prednisone-Bortezomib (MPV) — Results of the Dutch HOVON 123 Study

Geriatric Impairments and Low Muscle Mass Are Associated with Treatment Discontinuation and Overall Survival in Newly Diagnosed Non-Transplant Eligible Multiple Myeloma Patients (nte-NDMM) Treated with Dose-Adjusted Melphalan-Prednisone-Bortezomib (MPV) — Results of the Dutch HOVON 123 Study

Identification of Predictive Factors for Overall Survival at Baseline and during Azacitidine Treatment in High-Risk Myelodysplastic Syndromes Treated in the Clinical Practice

Background. 5-Azacitidine (5-AZA) had changed the therapeutic approach to intermediate-2/high IPSS risk myelodysplastic syndromes (MDS) improving the outcome of patients, even in the absence of a complete response. However, real-life experiences have reported contradicting results compared to the AZA001 randomized study. Aim of our analysis was to identify the clinico-biological features at baseline and during treatment associated with the overall survival (OS) and progression-free survival (PFS) at two years in a consecutive cohort of patients treated with hypometylating agent in the clinical practice. Moreover, we propose a new prognostic score for the identification of OS after the first four cycles of therapy.Patients and Method. We retrospectively analyzed a series of 110 MDS patients treated at a single institution with 5-AZA between September 2003 and January 2017. Patients were diagnosed according to the WHO 2016 criteria. 5-AZA was administered at a dose of 75 mg/m2 according to the 5+2+2 schedule every 28 days.Results. A male predominance was observed (male/female: 66%/34%) with a median age of 70 years (range 38-85). The median dose of 5-AZA received was 135 mg/day (range 105-150) after a median time from diagnosis of 2.3 months (range 0.1-119). Median duration of therapy was 9.5 cycles (range 1-77) with a median time on treatment of 8.5 months (range 1-86.7). OS of the whole cohort was 66.1% (CI 95% 57.2-76.4) at 1 year and 38.3% (CI 95% 29.4-49.9) at 2 years. Seventy-seven patients (70%) performed four cycles of therapy. According to the IWG criteria, 42 patients (54.5%) achieved a complete remission (CR), 11 (14.2%) a partial remission (PR), 17 (22.4%) maintained a stable disease (SD), 2 (2.5%) and 5 (6.4%) presented a progression disease (PD) and a failure, respectively. The 2-year OS was 68% in patients who obtained a CR/PR, 20% in patients with SD and 16% in patients with PD/failure (p<0.001). No differences in terms of OS were observed for gender (p=0.622) and age at baseline (<65years, 65-75 and >75 years, p=0.075). The baseline bone marrow blasts percentage did not impact on OS and PFS (OS, p=0.867; PFS, p=0.611). According to the Revised International Prognostic Score (R-IPSS), 22 (20%), 46 (42.8%) and 42 (38.2%) patients were classified as intermediate, high and very high-risk patients, respectively. We identified that the very high-risk group had an inferior 2-year OS (17%) compared to intermediate-group patients (64%, p<0.001). Indeed, we did not find significant difference according to the IPSS stratification (intermediate 42% vs high-risk 22%, p=0.253). Transfusion-independency at baseline was identified as a favorable prognostic factor on 1-year (66.8%) and 2-year OS (43.4%) compared to patients with transfusion dependency (36.4% and 22.2% if they required 1 unit/month or more than 1 unit at baseline at 2 years, p<0.001). After four cycles received, the persistence of bone marrow blasts >10% identified patients with a worse outcome, with a 2-year OS of 9.4% compared to 60.3% for patients with 0-5% blasts and 44.7% for patients with 5-10% blasts (p=0.002). The occurrence of one infection during the first four cycles impacted on the 2-year OS (31.6% vs 58.3% in patients without, p=0.032). We applied a dynamic prognostic score according to age, cytogenetic risk, transfusion need, number of 5-AZA cycles performed and type of response after the fourth cycle (Table 1): the combination of these variables identified 3 categories of risk with a significantly different 2-year OS: low-risk (72.3%), intermediate (19.8%) and high-risk (8.9%) (p<0.001, Fig. 1).Conclusions. Our results in a large and consecutive MDS cohort treated outside of clinical trials defined prognostic factors, such as transfusion dependency, persistence of >10% blasts after four cycles and absence of infections, capable of identifying patients with a good outcome. A prognostic score is proposed that requires independent validations in similar cohorts of patients. DisclosuresRizzo:Sapienza University, Rome: Other: Resident in Hematology. Foà:NOVARTIS: Speakers Bureau; CELTRION: Other: ADVISORY BOARD; GILEAD: Speakers Bureau; JANSSEN: Other: ADVISORY BOARD, Speakers Bureau; ROCHE: Other: ADVISORY BOARD, Speakers Bureau; CELGENE: Other: ADVISORY BOARD, Speakers Bureau; AMGEN: Other: ADVISORY BOARD; ABBVIE: Other: ADVISORY BOARD, Speakers Bureau; INCYTE: Other: ADVISORY BOARD. Breccia:Pfizer: Honoraria; Novartis: Honoraria; BMS: Honoraria; Incyte: Honoraria.

Predictive factors of benefit from iodine-125 brachytherapy for hepatocellular carcinoma with portal vein tumor thrombosis

PurposeThe aims of this study were to evaluate treatment responses and predictive factors for overall survival (OS) in hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT) treated with iodine-125 (125I) brachytherapy. Methods and MaterialsSeventy-seven HCC patients with PVTT underwent 125I brachytherapy after transcatheter arterial chemoembolization. Clinical, laboratory, and radiological evaluation were performed before and after treatment, as well as at 4–6 weeks intervals for 7 years to assess the efficacy and toxicity of therapy. Treatment response was assessed using modified response evaluation criteria in solid tumors. OS and predictive factors for each subgroup were evaluated after treatment. ResultsIn total, 11 patients (14.29%) achieved complete response, and 41 patients (53.25%) achieved partial response. The response rate (complete response + partial response) was 67.53% (52/77). The median OS was 9 months. The multivariable Cox regression model indicated that post-treatment tumor size with PVTT (p = 0.016, hazard ratio [HR] = 1.889, 95% confidence interval [CI]: 1.127 to 3.166) and baseline hemoglobin (p = 0.013, HR=0.518, 95% CI: 0.308 to 0.872) and alkaline phosphatase (p = 0.002, HR=2.275, 95% CI: 1.338 to 3.868) levels were significant independent predictors of OS. Conclusions125I brachytherapy results in favorable treatment responses in HCC patients with PVTT. Notably, post-treatment tumor size and baseline hemoglobin and alkaline phosphatase levels are significant independent predictive factors for OS and provide the most predictive information regarding OS.

Predictive factors of overall survival in primary intracranial pure choriocarcinoma

The incidence of primary intracranial pure choriocarcinoma (PIPC) is extremely rare. Only several case and case series have been previously reported; therefore, there is still lack of knowledge about the prognosis and its standard treatment. We performed a collective study of all reported cases of PIPC to identify the predictive factors related with OS. A comprehensive search was performed on Pubmed’s electronic database using the terms “primary intracranial choriocarcinoma” and “malignant germ cell tumor”. Data about gender, various location, the presence of intratumoral hemorrhage, metastasis and treatment modalities were extracted from the published articles and we analyzed the overall survival based on this predictive factors. 51 cases were eligible and met the inclusion criteria. The majority of the patients were in the child population (44.7%) age between 6 and 12 years old. 77.1% of the patient were male and 22.9% were female. Tumor located other than suprasellar and pineal area showed better prognosis. Median OS of PIPC was 22 months. Patient underwent gross total resection had better outcomes compared with those who only had partial or subtotal resection. Adjuvant therapy (especially chemotherapy) significantly improved OS (p = 0.000, log-rank test). PIPC is chemosensitive and metastasis is the predictive factor for poor prognosis.

Outcomes of Curative (Chemo)Radiotherapy for Patients Who Are Borderline for Curative Management of Squamous Cell Carcinoma of Head and Neck

Appropriate selection of head and neck cancer (HNC) patients for curative versus palliative treatment is one of the most difficult clinical decisions. The aims of this study were to 1) review the outcomes of curative intent treatment of HNC patients with borderline curability, and 2) assess the utility of a previously devised patient selection algorithm for curative treatment. A single institution retrospective review of patients with mucosal squamous cell carcinoma treated with curative intent between January 1 2004 and December 31 2011. Criteria for borderline curability included one or more of;1) T4 and/or N3 disease; 2) ECOG performance status >/=2; 3) age >/=80 years. A total of 199 patients were identified. One hundred thirty-seven had T4/N3 disease, 48 were >/=80 years, and 40 were >/=ECOG 2. Overall survival (OS) at 2 and 5 years was 67% (95% CI:60-74) and 45% (95% CI: 39-53) respectively. The 2-year and 5-year progression free survival (PFS) were 62% (95% CI: 55-69) and 39% (95% CI: 33-47), respectively. On multivariate analysis, independent predictive factors for overall survival were adult comorbidity evaluation-27 (ACE-27) grade and ECOG status. Thirty-three of the 199 patients should not have received curative intent treatment according to the algorithm. These patients had significantly poorer treatment completion rates and OS and PFS. ACE-27 and ECOG status are a strong and independent prognostic factors for survival among HNC patients of borderline curability. Our patient selection algorithm seems a useful tool to appropriately select patient who are borderline for curative (chemo)radiation treatment.

Prognostic Factors of Anaplastic Thyroid Carcinoma: An Egyptian Single Institution Experience

Background: Anaplastic thyroid carcinoma is an extremely aggressive cancer that has a very poor outcome. We have analyzed predictive factors for overall survival and different therapeutic modalities that could help to determine the optimal therapy for this carcinoma.Methods: We performed a retrospective analysis of data from 54 cases of anaplastic thyroid carcinoma to evaluate demographic, pathological, and clinical characteristics, along with therapeutic modalities that affected survival. The Kaplan-Meier curve was used to visualize the cumulative probability of survival and comparison among/between groups was performed with the log-rank test. A multivariate Cox proportional hazards model was used to examine overall survival.Results: We observed overall survival percentages of 50% (one-year), 25% (2- year), and 5.6% (5-year). The 2-year overall survival was 41.7% for stage IVA, 31.5% for stage IVB, and 7.4% for stage IVC (P= 0.04). The 2-year overall survival rates were 59.3% for patients with negative margins, 30.1% for those with positive margins, and 0.0% in the group without thyroidectomy (P=0.005). Surgery plus postoperative radiotherapy indicated better 2-year overall survival (56%) compared to surgery alone (34.7%, Pone month, no reported metastasis at presentation, negative surgical margins, surgery, radiotherapy, and/or chemotherapy.Conclusion: Anaplastic thyroid carcinoma is an aggressive cancer with a very poor prognosis. Multimodality treatment may improve overall survival in these patients. Duration of symptoms, primary tumor size, distant metastases, surgical treatment, surgical margin status, radiotherapy, and chemotherapy are independent factors that affect prognosis.

Outcomes for Patients with Non-metastatic Triple-negative Breast Cancer in New Zealand

AimsTriple-negative breast cancer (TNBC) has inferior outcomes to other subtypes of breast cancer. We studied the demographics and baseline breast cancer characteristics of patients in New Zealand with TNBC and assessed survival outcomes and prognostic/predictive factors. Materials and methodsWe searched the New Zealand breast cancer registry database and identified patients with TNBC without distant metastatic disease. We retrieved demographic, tumour characteristic and treatment information. Locoregional recurrence-free survival, breast cancer-specific survival (BSS), metastasis-free survival (MRFS) and overall survival were determined. Predefined univariate and multivariate analyses were carried out investigating the association of survival outcomes with treatment and tumour characteristics. ResultsIn total, 1390 patients were identified, with a median follow-up of 3.5 years. The median age was 55 years. Thirty-eight per cent were node positive and 79% were grade III. Mastectomy was carried out in 53%, adjuvant radiation delivered in 66% and chemotherapy in 69%. The significant predictive factors for overall survival, BSS and MRFS were radiotherapy, chemotherapy and neoadjuvant chemotherapy. The significant prognostic indicators were lymphovascular invasion, nodal status and tumour size. On Kaplan–Meier analysis, the 5 year overall survival was 72%. The median time to death for those who died was 3.55 years with 92% of deaths within 5 years. Seventy-four per cent of patients had distant metastasis as a first recurrence and isolated local recurrences occurred in only 4.5%. Metastatic disease occurred in lung (55.9%) and was in multiple sites in 51%. ConclusionWe report a large population-based series of TBNC without distant metastatic disease at diagnosis highlighting the unique behavioural characteristics of TNBC. Traditional therapies are positively associated with survival outcomes, and yet, particularly in the setting of recurrent disease, prognosis remains poor. Increased research into more effective systemic agents and the most effective timing of delivery of these may result in improved outcomes.

Significant predictors of overall survival in patients with hepatocellular carcinoma after surgical resection.

BackgroundThe predictive factors of overall survival after hepatectomy for HCC remain controversial and need to be investigated.MethodsIn total, 535 consecutive HCC patients undergoing resection were included and their clinicopathological data and overall survival were recorded. Both the tumor and adjacent non-tumor (ANT) tissues were subjected to immunohistochemistry analysis for the expression of autophagy-related markers.ResultsDeath was observed for 219 patients, and the cumulative overall survival rates at 1, 3, 5 and 7 years were 91.0%, 72.3%, 58.8%, and 27.7%, respectively. In the multivariate analysis, mortality was significantly associated with the following: diminished LC3 expression in both the tumor and ANT tissues, in the HCC tissues alone and in the ANT tissues alone (hazard ratio/95% confidence interval: 6.74/2.052–22.19, 6.70/1.321–33.98 and 2.58/1.499–4.915, respectively); recurrent HCC (5.11/3.136–8.342); HBV infection (2.75/1.574–4.784); cirrhosis (1.78/1.059–2.974); and antiviral therapy (0.42/0.250–0.697). The 5-year overall survival rates were 70.2%, 57.3%, 49.6% and 10.7% for patients with positive LC3 expression in both tissue types, in the HCC tissues alone, in the ANT tissues alone, and in neither tissue type, respectively. The 5-year overall survival rates were 56.7%, 47.3%, 51.2% and 38.7% for patients with HBV-related HCC, cirrhosis, no antiviral therapy, and recurrent HCC, respectively, and these rates were significantly lower than those in their counterparts.ConclusionsPatients with recurrent HCC, HBV-related HCC, cirrhosis, and the absence of antiviral therapy showed significantly lower overall survival rates. Furthermore, LC3 expression in both the tumor and liver microenvironments were significantly predictive of overall survival after resection for HCC.

Impact of histological tumor positive resection after pancreatoduodenectomy in patients with ductal adenocarcinoma and lymph node invasion

Introduction: In patients with pancreatic ductal adenocarcinoma (PDAC), complete tumor resection (R0) has been proven to improve overall survival (OS). The present study aimed to compare OS after R0 and R1 resections among patients with PDAC and lymph node invasion who underwent pancreatoduodenectomy. Methods: All consecutive PDAC patients of our prospectively-maintained pancreas database who underwent pancreatoduodenectomy were retrospectively analyzed (2000-2015). Only patients without neoadjuvant treatment were included. R0 resection was defined as absence of microscopic cancer cells at resection margin (1-mm clearance requirement). OS was calculated using Kaplan-Meier method. Results: During the study period, 192 consecutive patients underwent upfront pancreatoduodenectomy. On histopathology, 165 patients had lymph node invasion (86%), while 27 had no lymph node invasion (14%). Among patients with lymph node invasion (n=165), 92 had R0 resection (56%), 61 R1 resection (37%), and 12 R2 resection (7%). The 12 R2 resections were excluded (median OS: 14 months). Preoperative characteristics and demographics of R0 and R1 groups were similar. Overall complication rates (Clavien II-V) were similar in both groups (53/92=58% vs. 41/61=67%, p=0.232). Median OS was 24 months for the R0 and R1 groups (p=0.725). Recurrence rate was 59% for the R0 group and 64% for the R1 group (p=0.533). Multivariate Cox proportional hazards model did not identify the R status or any other item as predictive factor for OS in patients with lymph node invasion. Conclusion: In PDAC patients who underwent upfront pancreatoduodenectomy without neoadjuvant treatment, the R status did not influence OS in case of lymph node invasion.

Overall survival of pseudomyxoma peritonei and peritoneal mesothelioma patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy can be predicted by computed tomography quantified sarcopenia

BackgroundMalnutrition is associated with increased postoperative morbidity in abdominal surgery. This study aimed to determine if sarcopenia and/or abdominal fat composition could predict postoperative outcomes for patients undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for pseudomyxoma peritonei (PMP) and peritoneal mesothelioma (PM). MethodsAll patients who underwent a complete CRS-HIPEC for PMP and PM, between January 2009 and September 2017, were retrospectively studied. Preoperative computed tomography (CT) was used to measure the cross-sectional surface of skeletal muscle mass and adipose tissue (visceral and subcutaneous), at the level of the third lumbar vertebrae, to assess for sarcopenia and abdominal fat composition. ResultsAmong 115 patients, 82 were treated for PMP and 33 for PM. 64 patients (55.7%) were sarcopenic on the preoperative imagery. Major postoperative complications occurred in 63 patients (54.8%), without observable difference between sarcopenic and non-sarcopenic patients (56.2% vs. 52.9%; p = 0.723). The median overall survival (OS) was 73.3 for the patients with a normal muscle mass and 57.2 months for the sarcopenic patients (p = 0.05). ConclusionCT measured sarcopenia is an independent predictive factor for overall survival in patients treated for PMP and PM with CRS-HIPEC, but cannot predict postoperative morbidity.

Fibrosis in metastatic lymph nodes is clinically correlated to poor prognosis in colorectal cancer.

BackgroundTumor microenvironment including fibrosis has a pivotal role in cancer growth and distant metastasis. Fibrosis is a known risk factor for carcinogenesis, but its biological role in disease invasion and metastasis in colorectal cancer (CRC) remains unclear. In particular, there is no report on how fibrosis of metastatic lymph nodes (MLNs) in CRC contributes to prognosis.MethodsWe reviewed 94 colorectal adenocarcinoma patients with MLNs who underwent colectomy. Both the primary tumors and MLNs were analyzed for alpha-smooth muscle actin (α-SMA) expression and collagen deposition.ResultsHigher α-SMA expression and collagen deposition in MLNs were associated with significantly shorter relapse-free survival and overall survival in CRC patients. α-SMA expression in MLNs (HR, 1.53; p = 0.034) was independent predictive factor of overall survival in multivariate Cox proportional hazards regression analysis of clinicopathological factors. In the Stage III patient subgroup, α-SMA expression in MLNs was a strong prognostic marker (HR, 3.01; p = 0.006). On the other hand, higher α-SMA expression and collagen deposition in primary tumors were associated with short overall survival, but they were not significant factors in multivariate Cox regression analyses. In MLNs, the podoplanin signals co-localized with α-SMA expression and were confirmed by the dual immunofluorescence staining, implying that the MLN stromal cells were fibroblastic reticular cells.ConclusionBoth high collagen deposition and high α-SMA expression in MLNs predicted poor prognosis in CRC.

Radical thymectomy versus conservative thymomectomy in the surgical treatment of thymic malignancies.

Complete thymectomy is recommended for thymic malignancies to reduce local recurrence and the likelihood of the long-term development of myasthenia gravis (MG). Thymus-conserving surgery (thymomectomy) seems to yield similar results, but evidence is still limited. The objective of this study was to assess if the oncological outcome, in terms of overall survival (OS) and disease-free survival (DFS), are comparable between radical thymectomy vs. conservative thymomectomy patients, and to assess if the outcome of the video-assisted thoracoscopic surgery (VATS) approach was similar to open surgery approach. We retrospectively analyzed 157 consecutive patients with either resectable thymoma or thymic carcinoma from two Italian centers (Humanitas Research Hospital, Milan, and Humanitas Gavazzeni, Bergamo) between 1997 and 2013 who underwent thymomectomy or extended thymectomy with the VATS or open approach; the patients with Miastenia Gravis underwent radical thymectomy. The patients were followed through physical examinations and phone interviews. Thymomectomy and thymectomy were performed on 86 (54.8%) and 71 (45.2%) patients, respectively. Prognostic factors and comorbidities were comparable in the two groups. The median follow-up was 77 months. Cox proportional hazards model revealed that Masaoka advanced stage and thymic carcinoma of WHO classification were independent predictive factors for overall survival, but that the extent of surgery and the approach used (minimally invasive versus open) were not. Notably, five- and ten-year survival rates were similar in the two groups. In our experience, radical thymectomy and conservative thymomectomy did not differ in terms of disease-free and overall survival rates. In nonmyasthenic patients with early-stage resectable thymic malignancy, minimally invasive thymomectomy provided equivalent results to open thymectomy. Our results should be interpreted with caution due to the retrospective nature of the study. Well-designed, adequately-powered studies should be very welcome to increase the quantity and the quality of clinical evidence before incorporating this procedure in future guidelines.

Normalization of C-reactive protein levels following cytoreductive nephrectomy in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors is associated with improved overall survival

Introduction and objectivesPretreated C-reactive protein (CRP) has been suggested as one of the most important prognostic factors for metastatic renal cell carcinoma (mRCC). The aim of this study was to investigate the prognostic impact of the change in CRP level before and after cytoreductive nephrectomy (CN) in patients with mRCC treated with tyrosine kinase inhibitor. Materials and methodsThe CRP in 60 patients undergoing molecular targeted therapy for mRCC was measured before and after CN. The cutoff value of CRP was determined to be 0.5mg/dl.; thus, all patients were classified into lower CRP groups and higher ones according to their CRP before CN. The higher CRP group was further classified into 2 groups based on the kinetics after CN, “normalized CRP group” and “nonnormalized CRP group,” respectively. The overall survival (OS) of these groups was compared. ResultsThe median of the observation period was 21.6 months. The OS of patients in the lower CRP, normalized CRP, and nonnormalized CRP groups were 28.6, 23.1, and 12.3 months, respectively (nonnormalized CRP group vs. others, P<0.0001). Multivariate analysis revealed that the postoperative CRP level (≥0.5mg/dl) (hazard ratio = 0.218; 95% CI: 0.091–0.522; P = 0.0006) was an independent predictive factor of OS. ConclusionThe CRP level after CN can be a predictive factor for OS in patients with mRCC treated with tyrosine kinase inhibitor.

A predictive value of von Willebrand factor for early response to Bevacizumab therapy in recurrent glioma.

Bevacizumab (BV), a neutralizing monoclonal antibody against the vascular endothelial growth factor ligand, is recognized as a potent anti-angiogenic agent with antitumor activity. The aim of this single-center, retrospective, longitudinal study was to investigate the possible predictive value of baseline demographic, clinical and laboratory parameters for early 3-month response to BV therapy in patients with recurrent glioma. Forty-nine patients with recurrent glioma received BV at 10mg/kg intravenously every 3weeks alone or in association with chemotherapy were included in this study. Blood samples were collected from all patients before the first (baseline), the second and the third administration of BV. After 3months of BV therapy, patients with partial response were defined as responders whereas patients with stable or progressive disease were defined as non-responders. The median overall follow-up was 8months (range 1-73), the median overall survival (OS) was 8months (95% CI 6-10) and the median progression free survival (PFS) was 4months (95% CI 3-5). Thirty-five % of patients were responders and showed significantly lower von Willebrand factor (VWF) levels than non-responders at all sample times (p < .02 for all). Also, on multivariate analysis the baseline VWF value was the only predictor for an early response to BV therapy. Furthermore, D-dimer and prothrombin fragment 1+2 were predictive factors for OS while Karnofsky performance status resulted predictive for PFS. VWF antigen value is a possible predictive biomarker for an early 3-month response to BV therapy in recurrent glioma.