Circulating tumor DNA in advanced solid tumors: Clinical relevance and future directions.

The application of genomic profiling assays using plasma circulating tumor DNA (ctDNA) is rapidly evolving in the management of patients with advanced solid tumors. Diverse plasma ctDNA technologies in both commercial and academic laboratories are in routine or emerging use. The increasing integration of such testing to inform treatment decision making by oncology clinicians has complexities and challenges but holds significant potential to substantially improve patient outcomes. In this review, the authors discuss the current role of plasma ctDNA assays in oncology care and provide an overview of ongoing research that may inform real-world clinical applications in the near future.

Development and Validation of an Improved Pathological Nodal Staging System in Men with Prostate Cancer.

PURPOSE: Prostate cancer pathological nodal staging uses a single category for all node-positive patients. We sought to improve risk stratification by creating and validating a novel pathological nodal staging system incorporating number of metastatic lymph nodes (+LNs). MATERIALS AND METHODS: A total of 118,450 men who underwent radical prostatectomy for nonmetastatic prostate cancer in the National Cancer Database comprised our development cohort. Multivariable Cox proportional hazards analysis with restricted cubic splines was used to assess the nonlinear association between number of +LNs and overall mortality (OM). A novel staging system based on number of +LNs was derived by recursive partitioning analysis. The staging system was validated for prediction of OM and prostate-specific mortality in 105,568 men with nonmetastatic prostate cancer undergoing radical prostatectomy from the Surveillance, Epidemiology, and End Results database. Discrimination was assessed via Harrell's c-index. RESULTS: In multivariable Cox analysis, OM risk increased with higher number of +LNs up to 4 (HR 1.30 per each LN+, 95% CI 1.23-1.38), with a nonstatistically significant increase in risk (HR 1.05, 95% CI 0.99-1.11) beyond 4 +LN. In the development cohort, recursive partitioning analysis identified optimal cutoffs at 0 (N0: referent), 1 (N1: HR 1.40, 95% CI 1.25-1.58), 2 (N2: HR 1.67, 95% CI 1.40-1.99), 3-5 (N3a: HR 2.18, 95% CI 0.84-2.60) and ≥6 (N3b: HR 3.00, 95% CI 2.37-3.79) +LNs. In the validation cohort, these groups had markedly different 10-year OM (0+ LNs, N0: 15%; 1+ LN, N1: 35%; 2+ LNs, N2: 43%; 3-5 +LNs, N3a: 52%; and ≥6 +LNs, N3b: 59%; p <0.05) and prostate-specific mortality. The novel staging system improved survival classification over current staging for node-positive patients (optimism-corrected c-index 0.669 [95% CI 0.668-0.671] vs 0.649 [95% CI 0.648-0.651]). CONCLUSIONS: Pathological nodal staging in prostate cancer is improved with stratification by number of +LNs.

Favorable Survival with Non-curative Treatments for Patients with Early-Stage Hepatocellular Carcinoma After Liver Transplant Denial.

BACKGROUND: Many patients are not candidates for liver transplant for non-tumor-related reasons including medical comorbidities and non-adherence. The prognosis of patients with hepatocellular carcinoma (HCC) who are not liver transplant candidates in the era of locoregional therapy (LRT) including y90 is not well defined. AIMS: This study seeks to evaluate outcomes and the natural history of early-stage HCC in patients who were denied liver transplant listing due to non-tumor reasons and instead were treated with LRT. METHODS: A retrospective evaluation was performed for all patients who completed liver transplant evaluation with their tumor within Milan criteria but were denied due to non-tumor reasons and were treated with LRT at a single tertiary referral center. RESULTS: The 61 patients included had a favorable overall survival, with a median survival 60.3 months (86.9% at 1 year and 52.7% at 5 years). Patients with Child-Pugh A cirrhosis (n = 34) had significantly longer overall survival compared to those with Child-Pugh B/C cirrhosis (median survival of 70.3 months versus 26.1 months, p = 0.005). Survival in patients with Child-Pugh A at 1, 3, and 5 years was 97%, 80%, and 73%, respectively, compared to 74%, 41%, and 31% in patients with Child-Pugh B/C. CONCLUSIONS: In a small single-center cohort, patients with HCC who were denied liver transplant due to non-tumor reasons and underwent LRT and had Child-Pugh A cirrhosis had survival approaching the national average for patients who undergo liver transplantation. Patients with Child-Pugh B/C cirrhosis had significantly worse outcomes than those with Child-Pugh A.

Association of a Preoperative Leisure-Time Physical Activity With Short- and Long-term Outcomes of Patients Undergoing Curative Resection for Stage I to III Colorectal Cancer: A Propensity Score Matching Analysis.

BACKGROUND: Physical activity might be directly or indirectly linked to the risk of colorectal cancer and the prognosis of patients with colorectal cancer. OBJECTIVE: This study aimed to elucidate whether preoperative physical activity plays a role in reducing short-term postoperative complications and improving long-term survival of patients with colorectal cancer. DESIGN: This was a retrospective analysis of prospectively collected data. SETTINGS: This study was conducted at a department of colorectal surgery in a tertiary teaching hospital between January 1995 and December 2016. PATIENTS: Patients who underwent curative resection for stage I to III primary colorectal cancer were enrolled. According to the preoperative leisure-time weekly metabolic equivalent of task values, patients were divided into 2 groups: the metabolic equivalent of task <12 group and the metabolic equivalent of task ≥12 group. A 1:1 propensity score matching was used to reduce imbalance and selection biases based on 6 covariates, namely, age, sex, BMI, tumor location, tumor stage, and adjuvant chemotherapy administration. MAIN OUTCOME MEASURES: χ tests were used to analyze short-term postoperative complications. Kaplan-Meier analyses were used to evaluate disease-free survival and overall survival. RESULTS: In the matched cohort patients, significant differences in overall postoperative complications and mortality were observed in favor of the metabolic equivalent of task ≥12 group, although there was no difference in any single item of postoperative morbidity. The results of the Kaplan-Meier analysis and log-rank test demonstrated a significant survival benefit in the metabolic equivalent of task ≥12 group compared with the metabolic equivalent of task <12 group both for disease-free and overall survival. LIMITATIONS: This study is limited by its retrospective nature. CONCLUSIONS: This single-institute study provides evidence of the association of preoperative leisure-time physical activity with short-term postoperative morbidity and mortality, as well as long-term survival. See Video Abstract at http://links.lww.com/DCR/B189. ASOCIACIÓN DE ACTIVIDAD FÍSICA DE TIEMPO LIBRE PREOPERATORIA CON RESULTADOS A CORTO Y LARGO PLAZO DE PACIENTES SOMETIDOS A RESECCIÓN CURATIVA POR CÁNCER COLORRECTAL EN ESTADIO I-III: UN ANÁLISIS DE COINCIDENCIA DE PUNTAJE DE PROPENSIÓN ANTECEDENTES: LA ACTIVIDAD FíSICA PUEDE ESTAR DIRECTA O INDIRECTAMENTE RELACIONADA CON EL RIESGO DE CÁNCER COLORRECTAL Y EL PRONÓSTICO DE LOS PACIENTES CON CÁNCER COLORRECTAL.: Este estudio tuvo como objetivo dilucidar si la actividad física preoperatoria desempeña un papel en la reducción de las complicaciones postoperatorias a corto plazo y en mejorar la supervivencia a largo plazo de los pacientes con cáncer colorrectal.Este fue un análisis retrospectivo de datos recolectados prospectivamente.Este estudio se realizó en un departamento de cirugía colorrectal en un hospital universitario terciario entre Enero de 1995 y Diciembre de 2016.Se incluyeron pacientes sometidos a resección curativa por cáncer colorrectal primario en estadio I-III. De acuerdo con el equivalente metabólico semanal en el tiempo libre de los valores de la tarea preoperatorio, los pacientes se dividieron en dos grupos: el equivalente metabólico del grupo de tarea <12 y el equivalente metabólico del grupo de tarea ≥ 12. Se utilizó una coincidencia de puntaje de propensión 1: 1 para reducir los desequilibrios y los sesgos de selección basados en seis covariables, principalmente, edad, sexo, índice de masa corporal, ubicación del tumor, estadio del tumor y administración de quimioterapia adyuvante.Las pruebas de Chi-cuadrado se utilizaron para analizar las complicaciones postoperatorias a corto plazo. Los análisis de Kaplan-Meier se utilizaron para evaluar la supervivencia libre de enfermedad y la supervivencia general.en los pacientes de la cohorte emparejada, se observaron diferencias significativas en las complicaciones postoperatorias generales y la mortalidad a favor del equivalente metabólico del grupo de tareas ≥ 12, aunque no hubo diferencias en ningún elemento único de morbilidad postoperatoria. Los resultados del análisis de Kaplan-Meier y la prueba de log-rank demostraron un beneficio de supervivencia significativo en el equivalente metabólico del grupo tarea ≥ 12 en comparación con el equivalente metabólico del grupo tarea <12 tanto para la supervivencia libre de enfermedad como para la supervivencia general.Este estudio está limitado por su naturaleza retrospectiva.Este estudio de instituto único proporciona evidencia de la asociación de la actividad física preoperatoria en el tiempo libre con la morbilidad y mortalidad postoperatorias a corto plazo, así como la supervivencia a largo plazo. Consulte Video Resumen en http://links.lww.com/DCR/B189. (Traducción-Dr. Yesenia Rojas-Kahlil).

Effects of adding necitumumab to first-line chemotherapy in patients with stage IV non-small-cell lung cancer: Meta-analysis.

INTRODUCTION: Almost half of patients with non-small-cell lung cancer (NSCLC) are diagnosed at an advanced stage. Our aim was to assess the effects of adding necitumumab to chemotherapy in patients with stage IV NSCLC. MATERIAL AND METHODS: A comprehensive literature search was performed according to pre-specified inclusion and exclusion criteria. Data on overall survival, progression-free survival, objective response rate and adverse events were extracted. A meta-analysis was performed to obtain pooled hazard ratios (HR) and corresponding 95% confidence intervals (CI) for time-to-event data and pooled odds ratio (OR) with 95% CI for dichotomous outcomes. RESULTS: The meta-analysis included four randomized clinical trials with 2074 patients. The pooled results showed significant improvement for overall survival (HR = 0.87 (95% CI 0.79-0.95), p = 0.004) when necitumumab was added to chemotherapy in patients with advanced NSCLC. No statistically significant improvement was noted for progression-free survival and objective response rate (HR = 0.83 (95% CI 0.69-1.01), p = 0.06 and OR = 1.46 (95% CI 0.90-2.38), p = 0.13, respectively). Subgroup analysis showed that in patients with non-squamous NSCLC, there was no benefit in overall survival and objective response rate. Patients with advanced NSCLC who received necitumumab were at the highest odds of developing a skin rash (OR = 14.50 (95% CI 3.16-66.43), p = 0.0006) and hypomagnesaemia (OR = 2.77 (95% CI 2.23-3.45), p < 0.00001), while the OR for any grade ≥3 adverse event was 1.55 (95% CI 1.28-1.87, p < 0.00001). CONCLUSIONS: The addition of necitumumab to standard chemotherapy in a first-line setting in patients with stage IV NSCLC results in a statistically significant improvement in overall survival, while the results were not significant for progression-free survival and objective response rate.

Malignant fibrous neoplasms of long bones: analysis of the surveillance, epidemiology, and end results database from 1973 to 2015.

BACKGROUND: Malignant fibrous neoplasms (MFN) of long bones are rare lesions. Moreover, the prognostic determinants of MFN of long bones have not been reported. This study aimed to present epidemiological data and analyse the prognostic factors for survival in patients with MFN. MATERIALS AND METHODS: The Surveillance, Epidemiology, and End Results (SEER) programme database was used to screen patients with malignant fibrous neoplasms (MFN) of long bones from 1973 to 2015, with attention to fibrosarcoma, fibromyxosarcoma, periosteal fibrosarcoma and malignant fibrous histiocytoma. The prognostic values of overall survival (OS) and cancer-specific survival (CSS) were assessed using the Cox proportional hazards regression model with univariate and multivariate analyses. The Kaplan-Meier method was used to obtain OS and CSS curves. RESULTS: A total of 237 cases were selected from the SEER database. Malignant fibrous histiocytoma was the most common form of lesion in long bones. Multivariate analysis revealed that independent predictors of OS included age, stage, tumour size and surgery. Age, stage, tumour size and surgery were also independent predictors of CSS. Additionally, the most significant prognostic factor was whether metastasis had occurred at the time of initial diagnosis. CONCLUSION: Among patients with MFN of long bones, age (> 60 years), tumour size (> 10 cm), distant stage, and non-surgical treatment are factors for poor survival.

Analysis of key clinical features for achieving complete remission in stage III and IV non-small cell lung cancer patients.

BACKGROUND: Although development of immune checkpoint inhibitors and various molecular target agents has extended overall survival time (OS) in advanced non-small cell lung cancer (NSCLC), a complete cure remains rare. We aimed to identify features and treatment modalities of complete remission (CR) cases in stages III and IV NSCLC by analyzing long-term survivors whose OS exceeded 3 years. METHODS: From our hospital database, 1,699 patients, registered as lung cancer between 1st Mar 2004 and 30th Apr 2011, were retrospectively examined. Stage III or IV histologically or cytologically confirmed NSCLC patients with chemotherapy initiated during this period were enrolled. A Cox proportion hazards regression model was used. Data collection was closed on 13th Feb 2017. RESULTS: There were 164 stage III and 279 stage IV patients, including 37 (22.6%) and 51 (18.3%) long-term survivors and 12 (7.3%) and 5 (1.8%) CR patients, respectively. The long-term survivors were divided into three groups: 3 ≤ OS < 5 years, 5 years ≤ OS with tumor, and 5 years ≤ OS without tumor (CR). The median OS of these groups were 1,405, 2,238, and 2,876 days in stage III and 1,368, 2,503, and 2,643 days in stage IV, respectively. The mean chemotherapy cycle numbers were 16, 20, and 10 in stage III and 24, 25, and 5 in stage IV, respectively. In the stage III CR group, all patients received chemoradiation, all oligometastases were controlled by radiation, and none had brain metastases. Compared with non-CR patients, the stage IV CR patients had smaller primary tumors and fewer metastases, which were independent prognostic factors for OS among long-term survivors. The 80% stage IV CR patients received radiation or surgery for controlling primary tumors, and the surgery rate for oligometastases was high. Pathological findings in the stage IV CR patients revealed that numerous inflammatory cells existed around and inside resected lung and brain tumors, indicating strong immune response. CONCLUSIONS: Multiple line chemotherapies with primary and oligometastatic controls by surgery and/or radiation might achieve cure in certain advanced NSCLC. Cure strategies must be changed according to stage III or IV. This study was retrospectively registered on 16th Jun 2019 in UMIN Clinical Trials Registry (number UMIN000037078).

Unintended consequences of decreased PSA-based prostate cancer screening.

BACKGROUND: In May 2012, the US Preventive Services Task Force issued a grade D recommendation against PSA-based prostate cancer screening. Epidemiologists have concerns that an unintended consequence is a problematic increase in high-risk disease and subsequent prostate cancer-specific mortality. MATERIALS AND METHODS: To assess the effect of decreased PSA screening on the presentation of high-risk prostate cancer post-radical prostatectomy (RP). Nine high-volume referral centers throughout the United States (n = 19,602) from October 2008 through September 2016 were assessed and absolute number of men presenting with GS ≥ 8, seminal vesicle and lymph node invasion were compared with propensity score matching. RESULTS: Compared to the 4-year average pre-(Oct. 2008-Sept. 2012) versus post-(Oct. 2012-Sept. 2016) recommendation, a 22.6% reduction in surgical volume and increases in median PSA (5.1-5.8 ng/mL) and mean age (60.8-62.0 years) were observed. The proportion of low-grade GS 3 + 3 cancers decreased significantly (30.2-17.1%) while high-grade GS 8 + cancers increased (8.4-13.5%). There was a 24% increase in absolute numbers of GS 8+ cancers. One-year biochemical recurrence rose from 6.2 to 17.5%. To discern whether increases in high-risk disease were due to referral patterns, propensity score matching was performed. Forest plots of odds ratios adjusted for age and PSA showed significant increases in pathologic stage, grade, and lymph node involvement. CONCLUSIONS: All centers experienced consistent decreases of low-grade disease and absolute increases in intermediate and high-risk cancer. For any given age and PSA, propensity matching demonstrates more aggressive disease in the post-recommendation era.

Early Esophageal Cancer: A Gastroenterologist's Disease.

Traditionally, early esophageal cancer (i.e., cancer limited to the mucosa or superficial submucosa) was managed surgically; the gastroenterologist's role was primarily to diagnose the tumor. Over the last decade, advances in endoscopic imaging, ablation, and resection techniques have resulted in a paradigm shift-diagnosis, staging, treatment, and surveillance are within the endoscopist's domain. Yet, there are few reviews that provide a focused, evidence-based approach to early esophageal cancer, and highlight areas of controversy for practicing gastroenterologists. In this manuscript, we will discuss the following: (1) utility of novel endoscopic technologies to identify high-grade dysplasia and early esophageal cancer, (2) role of endoscopic resection and imaging to stage early esophageal cancer, (3) endoscopic therapies for early esophageal cancer, and (4) indications for surgical and multidisciplinary management.

Opportunity Lost? Diagnostic Laparoscopy in Patients with Pancreatic Cancer in the National Surgical Quality Improvement Program Database.

BACKGROUND: Routine preoperative staging in pancreas cancer is controversial. We sought to evaluate the rates of diagnostic laparoscopy (DLAP) for pancreatic cancer. METHODS: We queried the National Surgical Quality Improvement Program for patients with pancreas cancer (2005-2013) and compared groups who underwent DLAP, exploratory laparotomy (XLAP), pancreas resection (RSXN) or therapeutic bypass (THBP). We compared demographics, comorbidities, postoperative complications, 30-day mortality (Chi-square P < 0.05) and trends over time (R2 0-1). RESULTS: We identified 17,138 patients (RSXN 81.8%, XLAP 16.5%, THBP 8.2%, and DLAP 12.9%), with some having multiple CPT codes. Only 10.3% (n = 1432) of RSXN patients underwent DLAP prior to resection. XLAP occurred in 49.5% of non-RSXN patients, of whom 67.1% had no other operation. The percentage of patients undergoing RSXN increased 20.3% over time (R2 0.81), while DLAP decreased 52.6% (R2 0.92). XLAP patients without other operations decreased from 4.2 to 2.4%, although not linearly (R2 0.31). Only 10.3% of XLAP had a diagnostic laparoscopy as well, leaving nearly 90% of these patients with an exploratory laparotomy without RSXN or THBP. DISCUSSION: Diagnostic laparoscopy for pancreas malignancy is becoming less common but could benefit a subset of patients who undergo open exploration without resection or therapeutic bypass.

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

PURPOSE: The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. METHODS: Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. RESULTS: Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P < 0.0001; OR = 0.21, 95% CI 0.14-0.31) was more frequent in the studied group, unlike extracapsular invasion, which was significantly more often present in patients with DTC but without CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). CONCLUSIONS: The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

The changes in FIGO staging for carcinoma of the cervix uteri.

INTRODUCTION: The carcinoma of the cervix uteri is the fourth most common cancer in women worldwide and more than 85% of these cases occur in developing countries. Altogether 822 new cases were found in the Czech Republic during 2016 which means the incidence 15,3 new diseases/100,000 women. OBJECTIVE: To provide an overview of changes in FIGO (International Federation of Gynecology and Obstetrics) staging for carcinoma of the cervix uteri with an incorporation of possible imaging methods and/or pathological findings, and clinical assessment of tumor size and extent. SETTINGS: Gynecologic Oncology Center, Department of Gynecology and Obstetrics, Hospital Na Bulovce and 1st Medical School of Charles University, Prague; Gynecologic Oncology Center, Department of Gynecology and Obstetrics, General Faculty Hospital and 1st Medical School of Charles University, Prague; Institute of Radiation Oncology, Hospital Na Bulovce, Prague. METHODS: For this review, we have used the results of studies, review articles, and guidelines of oncogynecologic organisations on the cervical cancer published in English. They were identified through a search of literature using PubMed, MEDLINE-Ovid, Scopus and Cochrane Library with the keywords. We summarize the new classification, main changes compared to the former one and their clinical impact. CONCLUSION: Lateral extension measurement is removed in the stage IA, the only criterion is the measured deepest invasion.

A retrospective prognostic evaluation analysis using the 8th edition of the American Joint Committee on Cancer staging system for breast cancer.

PURPOSE: Breast cancer is a group of diseases with different intrinsic molecular subtypes. However, anatomic staging alone is insufficient to determine prognosis. The present study analyzed the prognostic value of the American Joint Committee for Cancer (AJCC) 8th edition cancer staging system. METHODS: This retrospective, single-center study included breast cancer cases diagnosed from January 1999 to December 2008. We restaged patients based on the 8th edition AJCC cancer staging system and analyzed the prognostic value of the anatomic and prognostic staged groups. Follow-up data including disease-free survival (DFS), overall survival (OS), and clinic-pathological data were collected to analyze the differences between the two staging subgroups. RESULTS: The study enrolled 7458 breast cancer patients with a 98.7-month median follow-up. Both the 5-year DFS and OS were significantly different between the anatomic and prognostic staged groups. The 5-year OS according to disease subtype was as follows: hormone receptor-positive/human epidermal growth factor receptor 2-negative [HR(+)/HER2(-)], 90.9%; HR(+)/HER2(+), 84.7%; HR(-)/HER2(+), 81.1%; and HR(-)/HER2(-), 80.9%. According to the anatomic stage, the 5-year OS of patients with stage III HR(+)/HER2(-) disease was superior to that of patients with stage II HR(-)/HER2(-) disease (88.3 vs. 86.5%). Per the prognostic stage, both the 5-year DFS and OS rates of patients with stage II HR(-)/HER2(-) disease were higher than those of patients with stage III HR(+)/HER2(-) disease (90.1 and 94.3% vs. 79.1 and 88.9%). CONCLUSIONS: The prognostic staging system is a refined version of the anatomic staging system and encourages a more personalized approach to breast cancer treatment.

Genetic and immunological biomarkers predict metastatic disease recurrence in stage III colon cancer.

BACKGROUND: Even though the post-operative outcome varies greatly among patients with nodal positive colon cancer (UICC stage III), personalized prediction of systemic disease recurrence is currently insufficient. We investigated in a retrospective setting whether genetic and immunological biomarkers can be applied for stratification of distant metastasis occurrence risk. METHODS: Eighty four patients with complete resection (R0) of stage III colon cancer from two clinical centres were analysed for genetic biomarkers: microsatellite instability, oncogenic mutations in KRAS exon2 and BRAF exon15, expression of osteopontin and the metastasis-associated genes SASH1 and MACC1. Tumor-infiltrating CD3 and CD8 positive T-cells were quantified by immunocytochemistry. Results were correlated with outcome and response to 5-FU based adjuvant chemotherapy, using Cox's proportional hazard models and integrative two-step cluster analysis. RESULTS: Distant metastasis risk was significantly correlated with oncogenic KRAS mutations (p = 0.015), expression of SASH1 (p = 0.016), and the density of CD8-positive T-cells (p = 0.007) in Kaplan-Meier analysis. Upon multivariate Cox-regression analysis, KRAS mutation (p = 0.008) and density of CD8-positive TILs (p = 0.009) were retained as prognostic parameters for metachronous distant metastasis. Integrative two-step cluster analysis was used to combine all genetic markers, allowing stratification of patient subgroups. Post-operative distant metastasis risk ranged from 31% (low-risk) to 41% (intermediate), and 57% (high-risk) (p = 0.032). Increased expression of osteopontin (p = 0.019) and low density of CD8-positive T-cells (p = 0.043) were significantly associated with unfavourable response to 5-FU. CONCLUSIONS: Integrative biomarker analysis allows stratification of stage III colon cancer patients for the risk of metastatic disease recurrence and may indicate response to 5-FU. Thus, biomarker analysis might facilitate the use of adjuvant therapy for high risk patients.

Evolution in Prostate Cancer Staging: Pathology Updates From AJCC 8th Edition and Opportunities That Remain.

The Tumor-Nodes-Metastasis system at the core of prognostic staging has been recently updated in the American Joint Committee on Cancer (AJCC) 8th edition, published in 2016. For prostate cancer, significant changes in staging of organ-confined disease, inclusion of a new grade grouping, and provision of levels of evidence for these modifications are part of what differentiates the 8th edition AJCC from prior iterations. Herein, the rationale underlying these changes is detailed. In addition, data elements not well represented in the present system are highlighted as opportunities for fresh study that may impact future AJCC classifications.

Expression and clinical significance of Caveolin-1 in prostate Cancer after transurethral surgery.

BACKGROUND: Prostate cancer is a common malignancy of the male genitourinary system that occurs worldwide. The current research aims to investigate caveolin-1 expression in prostate cancer tissue and its relationship with pathological grade, clinical pathologic staging, and preoperative prostate-specific antigen (PSA) levels. METHODS: From January 2012 to December 2014, samples from 47 patients with prostate cancer who had received transurethral prostatic resection (TURP) and 20 patients with benign prostatic hyperplasia were collected at the First Affiliated Hospital of Guangxi Medical University. Caveolin-1 was detected by streptavidin-perosidase (SP) immunohistochemical staining in pathological tissue slices. The results were statistically analyzed for pathological grade, clinical stage, and preoperative PSA level. RESULTS: The expression of caveolin-1 was significantly higher in prostate cancer samples than in benign prostatic hyperplasia samples (P < 0.05), and caveolin-1 expression was significantly different among the pathological grades of poorly, moderately and well-differentiated prostate cancer (P < 0.05). The difference in caveolin-1 expression was significant for different clinical stages (T1-T2 and T3-T4) of prostate cancer (P < 0.05). The difference in caveolin-1 expression was not significant among samples with different preoperative PSA levels (0-10, 10-100 and > 100 µg/L) (P > 0.05). CONCLUSIONS: Caveolin-1 is closely related to the pathological grade and clinical stage of prostate cancer after transurethral surgery, and it may be a novel tumor marker for prostate cancer. The expression of caveolin-1 is not associated with preoperative serum PSA levels.

Modified risk stratification grouping using standard clinical and biopsy information for patients undergoing radical prostatectomy: Results from SEARCH.

INTRODUCTION: Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions. However, significant heterogeneity remains for those with unfavorable-risk disease. METHODS: This study included 3335 patients undergoing radical prostatectomy without adjuvant radiotherapy in the SEARCH database. High-risk patients were dichotomized into standard and very high-risk (VHR) groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), number of NCCN high-risk factors, and stage T3b-T4 disease. Similarly, intermediate-risk prostate cancer was separated into favorable and unfavorable groups based on primary Gleason pattern, PPBC, and number of NCCN intermediate-risk factors. RESULTS: Median follow-up was 78 months. Patients with VHR prostate cancer had significantly worse PSA relapse-free survival (PSA-RFS, P < 0.001), distant metastasis (DM, P = 0.004), and prostate cancer-specific mortality (PCSM, P = 0.015) in comparison to standard high-risk (SHR) patients in multivariable analyses. By contrast, there was no significant difference in PSA-RFS, DM, or PCSM between SHR and unfavorable intermediate-risk (UIR) patients. Therefore, we propose a novel risk stratification system: Group 1 (low-risk), Group 2 (favorable intermediate-risk), Group 3 (UIR and SHR), and Group 4 (VHR). The c-index of this new grouping was 0.683 for PSA-RFS and 0.800 for metastases, compared to NCCN-risk groups which yield 0.666 for PSA-RFS and 0.764 for metastases. CONCLUSIONS: Patients classified as VHR have markedly increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy.

Randomized phase III trial of prophylactic cranial irradiation versus observation in patients with fully resected stage IIIA-N2 nonsmall-cell lung cancer and high risk of cerebral metastases after adjuvant chemotherapy.

BACKGROUND: This study compared prophylactic cranial irradiation (PCI) with observation in patients with resected stage IIIA-N2 non-small-cell lung cancer (NSCLC) and high risk of cerebral metastases after adjuvant chemotherapy. PATIENTS AND METHODS: In this open-label, randomized, phase III trial, patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high cerebral metastases risk without recurrence after postoperative adjuvant chemotherapy were randomly assigned to receive PCI (30 Gy in 10 fractions) or observation. The primary end point was disease-free survival (DFS). The secondary end points included the incidence of brain metastases, overall survival (OS), toxicity and quality of life. RESULTS: This trial was terminated early after the random assignment of 156 patients (81 to PCI group and 75 to control group). The PCI group had significantly lengthened DFS compared with the control group, with a median DFS of 28.5 months versus 21.2 months [hazard ratio (HR), 0.67; 95% confidence interval (CI) 0.46-0.98; P = 0.037]. PCI was associated with a decrease in risk of brain metastases (the actuarial 5-year brain metastases rate, 20.3% versus 49.9%; HR, 0.28; 95% CI 0.14-0.57; P < 0.001). The median OS was 31.2 months in the PCI group and 27.4 months in the control group (HR, 0.81; 95% CI 0.56-1.16; P = 0.310). While main toxicities were headache, nausea/vomiting and fatigue in the PCI group, they were generally mild. CONCLUSION: In patients with fully resected postoperative pathologically confirmed stage IIIA-N2 NSCLC and high risk of cerebral metastases after adjuvant chemotherapy, PCI prolongs DFS and decreases the incidence of brain metastases.

Long-term results of chemoradiotherapy for stage II-III thoracic esophageal cancer in a single institution after 2000 -with a focus on comparison of three protocols.

BACKGROUND: To evaluate the long-term results of chemoradiotherapy (CRT) for stage II-III thoracic esophageal cancer mainly by comparing results of three protocols retrospectively. METHODS: Between 2000 and 2012, 298 patients with stage II-III thoracic esophageal cancer underwent CRT. Patients in Group A received two cycles of cisplatin (CDDP) at 70 mg/m(2) (day 1 and 29) and 5-fluorouracil (5-FU) at 700 mg/m(2)/24 h (day 1-4 and 29-32) with radiotherapy (RT) of 60 Gy without a break. Patients in Group B received two cycles of CDDP at 40 mg/m(2) (day 1, 8, 36 and 43) and 5-FU at 400 mg/m(2)/24 h (day 1-5, 8-12, 36-40 and 43-47) with RT of 60 Gy with a 2-week break. Patients in Group C received two cycles of nedaplatin at 70 mg/m(2) (day 1 and 29) and 5-FU at 500 mg/m(2)/24 h (day 1-4 and 29-32) with RT of 60-70 Gy without a break. Differences in prognostic factors between the groups were analyzed by univariate and multivariate analyses. RESULTS: The 5-year overall survival rates for patients in Group A, Group B and Group C were 52.4, 45.2 and 37.2%, respectively. The 5-year overall survival rates for patients in Stage II, Stage III (non-T4) and Stage III (T4) were 64.0, 40.1 and 22.5%, respectively. The 5-year overall survival rates for patients who received 1 cycle and 2 cycles of concomitant chemotherapy were 27.9 and 46.0%, respectively. In univariate analysis, stage, performance status and number of concomitant chemotherapy cycles were significant prognostic factors (p < 0.001, p = 0.008 and p < 0.001, respectively). In multivariate analysis, stage, protocol and number of concomitant chemotherapy cycles were significant factors (p < 0.001, p = 0.043 and p < 0.001, respectively). CONCLUSIONS: The protocol used in Group A may be an effective protocol of CRT for esophageal cancer. It may be important to complete the scheduled concomitant chemotherapy with the appropriate intensity of CRT.