Prognostic Factor For Disease Recurrence Research Articles

Evaluating the Effect of the Demographic, Trichoscopic and Laboratory Characteristics on The Recurrence of Alopecia Areata.

Alopecia areata (AA) has diverse disease characteristics and multiple factors may interfere with the prognosis of the disease. In this study, the factors affecting the AA recurrence were evaluated. A total of a hundred patients diagnosed with AA between June 2022 and March 2023 were included in this retrospective, cross-sectional study. The patients were divided into two groups according to the presence of outbreaks. Both groups were compared in terms of age, gender, disease duration, number of outbreaks, family history of AA, previous medical treatment history for AA, clinical type, disease severity, presence of accompanying nail findings, and trichoscopic and laboratory characteristics. Among 100 patients, male dominance was found (N = 69). Most of the patients had patchy disease (90/100), mild disease severity (88/100), and a solitary outbreak (65/100). Male gender, longer disease duration, family history, presence of S2 severity of alopecia tool score, trachyonychia, short vellus hairs in trichoscopic examination, hypothyroidism, and folic acid deficiency were factors for AA outbreaks. Male gender and the presence of a family member with AA in the family were defined as the independent prognostic factors for disease recurrence. While demographic, laboratory, and clinical findings are factors for AA outbreaks in the follow-up, male gender and family history should be considered independent predictors.

The Impact of Waiting Time-to-Surgery on Survival in Endometrial Cancer Patients.

Endometrial cancer (EC) is the most common gynecological cancer in developed countries and a standard treatment of surgery should be performed as expediently as possible. Delay time to surgery and survival was debated. The aim of this investigation was to evaluate the effect of time-interval between diagnosis and surgery (TDS) in EC patients with regards to prognosis and mortality rates. This retrospective study was conducted between January 2009 and May 2021 at Bhumibol Adulyadej Hospital, Thailand. Subjects were EC cases who underwent primary surgery during the study period. Cases with partial treatment were disqualified from the study. Subjects who underwent surgery before and after 6 weeks were classified as early and delayed surgery groups. Baseline and clinical characteristics were collected and analyzed. During the study period, 419 EC cases were recruited. The mean age of participants was 56.8 years. Two-thirds (338/491) of subjects were menopausal. Endometrioid histology (406/491) was the most common histology subtype. Five years disease free survival (DFS) of early and delayed surgery groups were comparable at a percentage of 82.5 and 83.0, respectively. Among advanced stage and non-endometrioid EC cases, the delayed surgery group had significantly shorter DFS than the early group. Advanced stage, high grade and positive lympho-vascular space invasion (LVSI) were independent factors for poor DFS. Predictive factors for mortality were advanced stage and tumor recurrence. The TDS was not a prognostic factor for disease recurrence or overall mortality. Time to surgery equal to or more than 6 weeks gave worse prognosis for DFS among advanced stage or non-endometrioid histology EC.

Comparison of Partial Versus Superficial or Total Parotidectomy for Superficial T1-2 Primary Parotid Cancers.

This study aimed to compare the oncological outcomes of partial versus superficial or total parotidectomy for superficial T1 or T2 primary parotid cancers and investigate their prognostic factors and recurrence patterns. The medical records of 77 patients with T1-2 primary parotid malignancies between May 2003 and March 2022 were retrospectively reviewed. Univariate and multivariate analyses were performed to evaluate the prognostic factors associated with overall survival, disease-free survival, and local and distant recurrence. The average follow-up duration was 70.2 months (range, 12-202 months). The 5-year overall and disease-free survival rates were 88.7% and 77.1%, respectively. Twenty-two patients underwent partial parotidectomy, and 55 underwent superficial or total parotidectomy. There were no significant differences in the disease recurrence (P=0.320) and mortality rates (P=0.884) of the partial and superficial or total parotidectomy groups. The mean duration of surgery was shorter and the overall complication rates were significantly lower in the partial group than in the superficial or total parotidectomy group (P=0.049). Sixteen cases of recurrence occurred during the study period (20.8%). Univariate analyses showed that high-grade tumors (P=0.006), lymphovascular invasion (P=0.046), and regional lymph node metastasis (P=0.010) were significant risk factors for disease recurrence. Multivariate analysis identified regional lymph node metastasis as an independent prognostic factor for disease recurrence (P=0.027), and lymphovascular invasion as an independent prognostic factor for overall survival (P=0.033). The conservative surgical approach of partial parotidectomy can yield oncological outcomes comparable to those of superficial or total parotidectomy with careful patient selection in T1-2 parotid cancers.

Recurrence-Free Survival and Disease-Specific Survival in Patients with Pancreatic Neuroendocrine Neoplasms: A Single-Center Retrospective Study of 413 Patients.

The prognosis and impact of different prognostic factors in pancreatic neuroendocrine neoplasms (pNEN) remain controversial. To investigate prognostic factors for recurrence-free survival and disease-specific survival in patients with pNEN, divided into three groups: patients undergoing surveillance (tumor size < 2 cm, group 1), patients followed after curative-intended surgery (group 2), and patients with unresectable disease or residual tumors after resection (group 3). A single-center retrospective study including consecutive patients over a 20-year period. Multivariate Cox regression analyses were performed to identify risk factors. 413 patients were included, with a mean (SD) age of 62 ± 14 years. In group 1 (n = 51), median (IQR) follow-up was 29 (21-34) months, and tumor size was 1.0 (0.8-1.4) cm. One progressed and had a tumor resection. In group 2 (n = 165), follow-up 59 (31-102) months, median tumor size 2 (1.2-3.4) cm, median Ki-67 index 5 (3-10)%, the 5-year recurrence rate was 21%. Tumor size (p < 0.001), Ki-67 index (p = 0.02), and location in the pancreatic head (p < 0.001) were independent risk factors. In group 3 (n = 197), follow-up 19 (6-46) months, median tumor size 4.2 (2.6-7.0) cm, Ki-67 index 17 (9-64)%, the median disease-specific survival was 22 (6-75) months-99 in NET G1; 54 in NET G2; 14 in NET G3; and 6 months in neuroendocrine carcinomas (NEC). Age (p = 0.029), plasma chromogranin A (p = 0.014), and proliferation, expressed by grade (p = 0.001) and Ki-67 index (p < 0.001), were risk factors. Growth in pNET < 2 cm requiring surgery was observed in 1/51. Tumor size, Ki-67 index, and location in the head were prognostic factors for disease recurrence, while age, plasma chromogranin A, and proliferation predicted mortality in patients with unresectable disease or residual tumors after resection.

Two-year outcomes of clinical N2-3 esophageal squamous cell carcinoma after neoadjuvant chemotherapy and immunotherapy from the phase 2 NICE study

ObjectiveThis study aims to report the 2-year outcomes of patients with clinical stage N2-3 esophageal squamous cell carcinoma who received neoadjuvant chemotherapy and immunotherapy followed by surgery from a phase 2 NICE trial. MethodsEligible patients with clinical stage N2-3 esophageal squamous cell carcinoma were screened and enrolled, then treated with regimen of nab-paclitaxel (100 mg/m2, days 1, 8, 15), carboplatin (area under the curve = 5, day 1), camrelizumab (200 mg, day 1) of two 21-day cycles and esophagectomy 4 to 6 weeks after the last chemotherapy. Oncologic outcomes, recurrence patterns, overall survival (OS), and recurrence-free survival (RFS) were explored. ResultsFrom November 20, 2019, to December 22, 2020, 60 patients were recruited. After a median follow-up of 27.4 months, disease recurrence was observed in 19 (37.3%) patients, with 5 (9.8%) locoregional recurrence, 9 (17.6%) distant metastasis, and 5 (9.8%) combined recurrence. Lung was the most commonly involved metastatic site. The median time to recurrence was 10.8 months (interquartile range, 7.5-12.7 months). The 2-year OS and RFS rates were 78.1% and 67.9%, respectively. Patients who achieved major pathologic response (MPR) had a significantly greater 2-year OS rate (91.4% vs 47.7%; P < .001) and RFS rate (77.1% vs 45.9%; P = .003). On multivariable analysis, MPR was indicated as an independent prognostic factor for disease recurrence (hazard ratio, 0.39; 95% confidence interval, 0.21-0.82; P = .029). ConclusionsIn patients receiving neoadjuvant chemotherapy and immunotherapy, distant metastasis remains the predominant recurrence pattern. MPR is associated with lower recurrence and better survival. Long-term results derived from randomized controlled trials are further required. Trial registration numberChiCTR1900026240.

Can CD34+CD38- lymphoblasts, as likely leukemia stem cells, be a prognostic factor in B-cell precursor acute lymphoblastic leukemia in children?

CD34+CD38- lymphoblasts as likely leukemia stem cells (LSCs) may be responsible for a worse response to treatment and may be a risk factor for recurrence in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The study objective was to assess the prognostic role of CD34+CD38- lymphoblasts in bone marrow on the day of BCP-ALL diagnosis. 115 patients with BCP-ALL, the median age of 4.5 years (range 1.5-17.9 years), gender: female 63 (54.8%) with BCP-ALL were enrolled; Group I (n = 90)-patients with CD34+CD38+ antigens and Group II (n = 20)-patients with CD34+CD38- antigens on the lymphoblast surface. A worse response on Days 8, 15, and 33 of therapy and at the end of treatment in Group II (CD34+CD38-) was more often observed but these differences were not statistically significant. A significantly higher incidence of BCP-ALL recurrence was in Group II. 1.In BCP-ALL in children, the presence of CD34+CD38- lymphoblasts at the diagnosis does not affect the first remission.2.In BCP-ALL in children, the presence of CD34+CD38- lymphoblasts at the diagnosis may be considered an unfavorable prognostic factor for disease recurrence.3.It is necessary to further search for prognostic factors in BCP-ALL in children.

Expression of the immune targets in tumor-infiltrating immunocytes of gestational trophoblastic neoplasia.

Objectives: To evaluate the expression of emerging immune targets in the tumor-infiltrating immunocytes (TIIs) of human gestational trophoblastic neoplasia (GTN) specimens, and to analyze the correlation between the expression patterns and prognosis of GTN patients. Methods: Between January 2008 and December 2017, patients who were diagnosed histologically with GTN were included in this study. The expression densities of LAG-3, TIM-3, GAL-9, PD-1, CD68, CD8, and FOXP3 in the TIIs were assessed independently by two pathologists blinded to clinical outcomes. The expression patterns and correlation with patient outcomes were analyzed to identify prognostic factors. Results: We identified 108 patients with GTN, including 67 with choriocarcinoma, 32 with placental site trophoblastic tumor (PSTT), and 9 with epithelioid trophoblastic tumor (ETT). Almost all GTN patients showed expression of GAL-9, TIM-3, and PD-1 in TIIs (100%, 92.6%, and 90.7%, respectively); LAG-3 was expressed in 77.8% of the samples. The expression densities of CD68 and GAL-9 were significantly higher in choriocarcinoma than that in PSTT and ETT. The TIM-3 expression density in choriocarcinoma was higher than that in PSTT. In addition, the expression density of LAG-3 in the TIIs of choriocarcinoma and PSTT was higher than that in ETT. There was no statistical difference in the expression pattern of PD-1 among different pathological subtypes. The positive expression of LAG-3 in tumor TIIs was a prognostic factor for disease recurrence, and patients with positive expression of LAG-3 in the TIIs had poorer disease-free survival (p = 0.026). Conclusion: Our study evaluated the expression of immune targets PD-1, TIM-3, LAG-3, and GAL-9 in the TIIs of GTN patients and found that they were widely expressed but not associated with patients' prognoses, excepting the positive expression of LAG-3 was a prognostic factor for disease recurrence.

Effect of skip metastasis to lateral neck lymph nodes on outcome of patients with papillary thyroid carcinoma.

Lymph node metastasis (N1) is a prognostic factor for disease recurrence in papillary thyroid carcinoma (PTC) patients. Skip metastasis is defined as only lateral N1 with negative central lymph nodes (LNs). The aim of this study was to explore the outcome of PTC patients with skip N1. All patients who underwent a total thyroidectomy with ipsilateral central and lateral LN dissection for PTC from 1999 to 2019 in a high-volume endocrine surgery centre were included in this study. Demographic and outcomes-recurrence and disease-specific survival (DSS)-were compared between three groups: N1a (central N1 only), N1b-CL (central and lateral N1), and N1b-Skip (lateral N1 without central LN involvement). During the study period, 3046 patients had surgery for PTC, including 1138 with N1 (37%, 860 women, mean age: 44.8years) comprising 474 N1a (42%), 513 N1b-CL (45%), and 151 N1b-Skip (13%). The median follow-up was 74months (range 12-216months). The recurrence rate in the N1b-Skip group was 13% (20/151) and 10% (47/474) in the N1a group. This was significantly lower than that in the N1b-CL group (27%, 140/513) (p < 0.0001). DSS at 10years was 99% for group N1a, 98% for the N1b-CL, and 99% in the N1b-Skip group. The recurrence rate of N1b-Skip patients was lower than that of N1b-CL patients and similar to that of N1a patients. This result could be used as an indication for the modality of radioiodine therapy, and for the pattern of follow-up procedures.

Current Status and Future Perspective on the Management of Lymph Node-Positive Prostate Cancer after Radical Prostatectomy.

Simple SummarypN1 after RP with PLND represents one of the most unfavorable prognostic factors for disease recurrence and cancer-specific mortality in prostate cancer. Treatment intensification may reduce risks of recurrence and cancer-specific mortality, but it may increase adverse events and impair quality of life. However, optimal management for pN1 patients remains unclear. Nevertheless, few randomized control trials for pN1 are under investigation, and then more research is needed to establish an optimal therapeutic strategy for patients with pN1. This review summarizes current evidence on the treatments available for men with pN1, summarizes RCTs that included pN1 prostate cancer, and also discusses future perspectives.Pathological lymph node involvement (pN1) after a pelvic lymph node dissection represents one of the most unfavorable prognostic factors for disease recurrence and cancer-specific mortality in prostate cancer. However, optimal management for pN1 patients remains unclear. Thus, the guideline from the European Association of Urology recommends discussing three following management options with pN1 patients after an extended pelvic lymph node dissection, based on nodal involvement characteristics: (i) offer adjuvant androgen-deprivation therapy, (ii) offer adjuvant androgen-deprivation therapy with additional radiotherapy and (iii) offer observation (expectant management) to a patient with ≤2 nodes and a prostate-specific antigen <0.1 ng/mL. Treatment intensification may reduce risks of recurrence and cancer-specific mortality, but it may increase adverse events and impair quality of life. Few randomized control trials for pN1 are under investigation. In addition, there are limited reports on the quality of life and patient-reported outcomes in patients with pN1. Therefore, more research is needed to establish an optimal therapeutic strategy for patients with pN1. This review summarizes current evidence on the treatments available for men with pN1, summarizes randomized control trials that included pN1 prostate cancer, and discusses future perspectives.

The prognostic factor for recurrence in advanced-stage high-grade serous ovarian cancer after complete clinical remission: a nested case-control study

BackgroundWomen with advanced-stage high-grade serous ovarian cancer (HGSOC) are likely to have a bad prognosis. Relapses are common in patients even with no evidence of disease after primary treatment. We aimed to identify the prognostic factors for disease recurrence in these patients.MethodsA nested case-control study was conducted in a large medical center in Southwest China. The primary outcome was recurrence of disease within 3 years after clinical remission (CR). Cox regression was used to calculate the time to event analysis in different groups.ResultsNinety-seven patients were finally included. Fifty-seven patients (58.8%) relapsed within 3 years after CR. Among all the variables, the difference in posttreatment CA-125 level was statistically significant (P <0.05) between the recurrent group and the progression-free group in both univariate and multivariable analysis. A cutoff value was set at the median level in the recurrent group (10 U/ml) to categorize patients into two arms. In Cox regression, the posttreatment CA-125 level was identified as a prognostic factor for recurrence with an OR of 1.05 (95% CI: 1.02–1.10, P = 0.033). The median time (from initiation of treatment) until relapse was 25 months for patients whose posttreatment CA-125 levels were higher than 10 U/ml, while it was undefined for patients whose posttreatment CA-125 level were ≤ 10 U/ml. Patients with a higher posttreatment CA-125 level showed an increased risk for OC relapse compared to those with a lower posttreatment CA-125 level. Furthermore, as shown in line graphs recording serum CA-125 levels during follow-up in each recurrent case, the increments of serum CA-125 levels were delayed in recurrent OC patients who had a posttreatment CA125 level ≤ 10 U/ml compared with those with a higher CA-125 level.ConclusionA low serum CA-125 level after primary treatment was a potential prognostic factor in women with advanced HGSOC.

A single centre's experience of 23 cases of total rhinectomy for the treatment of squamous cell carcinoma involving the nasal vestibule.

This study aims to analyse the oncological outcomes of total rhinectomy (TR) for squamous cell carcinomas (SCCs) involving the nasal vestibule, and to identify prognostic factors for disease recurrence. A retrospective single-centre study was conducted between September 2003 and February 2021 including all patients who underwent a TR for a SCC involving the nasal vestibule. 23 patients were included in the study. Tumours originated from the anterior septum (n = 12), vestibule (n = 8) or skin (n = 3). Six TRs (26.1%) were salvage procedures, after primary radiotherapy or partial rhinectomy. Seven patients had a concurrent neck dissection and 17 patients (73.9%) received adjuvant treatment (14 patients had radiotherapy and 3 had chemoradiotherapy). After a median follow-up of 32months, six patients (26.1%) presented with tumour recurrence. Three patients (13%) had nodal-only recurrence. The estimated 5-year overall survival, disease-free survival and disease-specific survival were 67.5%, 66.3% and 80.7%, respectively. Positive excision margins were a predictive factor for tumour recurrence (p = 0.0401). For SCCs involving the nasal vestibule that are not amenable to limited surgical resection, TR along with adjuvant radiotherapy provide good oncological outcomes and should be considered the main treatment option.

MAP17 Expression in Colorectal Cancer Is a Prognostic Factor for Disease Recurrence and Dismal Prognosis Already in Early Stage Disease

Background: Disease recurrence in colorectal cancer constitutes a major cause of significant cancer-associated morbidity and mortality. MAP17 is a small protein, and its overexpression in malignant tumors has been correlated with aggressive tumor phenotypes. The aim of the present study was to investigate the expression patterns of MAP17 in colorectal cancer specimens and to assess its clinical significance. Patients and Methods: Surgical specimens of 111 patients with primary resectable colorectal cancer constituted the study population. Expression of MAP17 was assessed by immunohistochemistry, and the results were correlated with clinical and survival data. Results: MAP17 was expressed in cancer cells and endothelial cells of tumor blood vessels. Expression of MAP17 more than 10% was correlated with advanced disease stage (p < 0.001), higher T classification (p = 0.007), the presence of lymph node metastasis (p < 0.001), vascular (p = 0.013) and perineural invasion (p = 0.012). Patients exhibiting MAP17 expression of more than 30% in cancer cells compared to those expressing MAP17 less than 10% demonstrated a significantly worse 3-year progression-free survival (35.2 vs. 91%, p < 0.001) and 5-year overall survival (40.8 vs. 91%, p < 0.001). Cox regression analysis confirmed MAP17 expression of more than 30% as a prognostic marker of progression free survival (HR 0.136, 95% CI = 0.056–0.329, p < 0.001) and overall survival (HR 0.144 [95% CI) = 0.049–0.419, p < 0.001) independent of other clinicopathological characteristics. Statistically significantly worse 3-year progression-free survival and 5-year overall survival was demonstrated in the subgroup analysis of patients with early stage cancer only and high expression of MAP17. Conclusions: High MAP17 expression in patients with colorectal cancer is a significant risk factor for cancer-associated morbidity and mortality already in early stage disease.

Tumor proximity to serosal surface as an independent prognostic factor in FIGO stage 1 endometrial cancer

Objective: Determine if tumor distance from serosal surface is an independent prognostic factor for disease recurrence and survival in stage 1 endometrial cancer. Methods: 747 patients diagnosed with stage 1 endometrial cancer between 1984 and 2015 were identified from an institutional database. This retrospective cohort was evaluated to assess differences in tumor distance from the serosal surface, histologic subtype, histologic grade, use of adjuvant treatment, recurrence rates and overall survival. Cox proportional hazard models were used to determine if variables of interest were related to recurrence and overall survival. Concordance correlation coefficients were used to compare our model to the 2009 International Federation of Gynecology and Obstetrics (FIGO) staging. Results: Tumor distance from serosal surface ranged from 0 mm–21 mm. 47 (8.7%) patients experienced recurrence. Patients with tumors located 5 mm or less from the serosal surface were 2.24 times more likely to experience recurrent disease (HR 2.24, 95% CI: 1.16 to 4.31, p = 0.02). Concordance rates for disease recurrence were 0.573 and 0.583 for our tumor distance model compared to the 2009 FIGO staging (95% CI: 0.568 to 0.579 and 95% CI: 0.577 to 0.589). Conclusions: Our study demonstrates that patients with tumors located 5 mm or less from the serosal surface have a two-fold increased risk of recurrence. Concordance rates are very similar between our model and the 2009 FIGO staging suggesting comparable predictability; these rates suggest there is room for improvement in both methods to predict disease recurrence and survival.

Factors affecting recurrence rates in women with borderline ovarian tumors.

e18055 Background: Borderline or low malignant potential tumors of the ovary (BOTs) make up approximately 15-20% of all ovarian neoplasms. These tumors are considered indolent and usually confer an excellent overall survival in women who are treated utilizing a conservative surgical approach. However, recurrence rates can approach 30%. The aim of this study was to compare the type and mode of surgery and its impact on outcomes in patients with BOTs. Methods: An Institutional Review Board approved, retrospective cohort study identified all patients at Long Island Jewish Medical Center, North Shore University Hospital and USC Medical Center with BOTs who underwent surgery between January 2008 and May 2018. Demographics and outcome measures were obtained from the medical records. Prognostic factors for disease recurrence were studied including histological subtypes type of surgical procedure, including minimally invasive or open ovarian cystectomy and oophorectomy. Results: 260 patients were identified. 226 of these women (88%) had stage I disease at the time of diagnosis. There were 26 recurrences noted in the cohort, a recurrence rate of 10 percent. The median age was 50 years old (range 16-86). 145 patients (56%) underwent minimally invasive surgical procedures compared to 115 (44%) who had open laparotomy. 30 (12%) of the women underwent an ovarian cystectomy and 230 (88%) had an oophorectomy. The median time to disease recurrence was 25 months (range 4-94 months). There was significant difference in the recurrence free survival between the patients who had minimally invasive procedures and those who had open laparotomy (hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.11-6.52). There was also significant difference in Recurrence Free Survival (RFS) and in those who underwent ovarian cystectomy and oophorectomy (HR 7.32, 95%CI 3.34-16.06). No difference in recurrence rates were noted between those with serous and mucinous histology. Conclusions: In this cohort of women with BOTs, the risk of recurrence was associated with minimally invasive surgery versus open laparotomy as well as ovarian cystectomy compared with oophorectomy. Conservative surgery for BOTs in young patients plays an important role for fertility preservation in these young women and can be curative. This study allows us to present additional information to address surgical approach and risk for disease recurrence in young women having fertility sparing and conservative surgery for BOTs.

HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer.

HER2 overexpression has been investigated as a potential biomarker and therapeutic target in biliary tract cancer (BTC), but a prognostic role of such alteration has not been demonstrated yet. We retrospectively evaluated HER2 protein expression by immunohistochemistry (IHC) in 100 patients with radically resected BTC. HER2 gene amplification was assessed by fluorescence in situ hybridization (FISH) in 2+ and 3+ cases at IHC. High HER2 protein expression was defined as either IHC 3+ or 2+ associated with FISH positivity. The primary objective of the study was to evaluate the prognostic role of HER2 overexpression in terms of disease-free survival (DFS) and overall survival (OS). Secondary endpoints were the prevalence of HER2 overexpression and the possible correlation with other clinicopathological features. HER2 overexpression was identified in 11 patients and was not related to other clinicopathological factors. DFS was significantly shorter in HER2-positive compared with HER2-negative patients (10.6 vs. 20.9 months, log-rank p = .017). HER2 confirmed its prognostic value for DFS at multivariate analysis (hazard ratio 2.512; 95% confidence interval, 1.232-5.125; p = .011) together with nodal stage (p < .001), resection margin (p = .027), and tumor site (p = .030). There was no difference in OS between HER2-positive and -negative patients (p = .068). HER2 overexpression represents an independent prognostic factor for disease recurrence in patients with BTC treated with potentially curative surgery. HER2 overexpression may play an independent role in promoting an aggressive behavior in resectable biliary tract cancer. This evidence could be helpful in improving prognostic stratification after resection and, primarily, should endorse the rationale to investigate HER2 as a therapeutic target in biliary tract cancer.

Neutrophilia and mortality in women with uterine carcinosarcoma

ObjectiveThe objective of this study was to investigate the relationship between pre-treatment absolute neutrophil count and clinical outcomes in patients with uterine carcinosarcoma.MethodsIn an Institutional Review Board approved, retrospective cohort...

Approaches to Integrating Biomarkers Into Clinical Trials and Care Pathways as Targets for the Treatment of Inflammatory Bowel Diseases

There is no consensus on the best way to integrate biomarkers into inflammatory bowel disease (IBD) research and clinical practice. The International Organization for the Study of Inflammatory Bowel Disease aimed to outline biomarker definitions, categories, and operating properties required for their use in registration trials and clinical practice. Using fecal calprotectin as an example, we provide a framework for biomarker development and validation in patients with IBD. We reviewed international society guidelines, regulatory agency guidance documents, and standardized reporting guidelines for biomarkers, in combination with publications on fecal calprotectin levels in patients with IBD. We assessed the validity of fecal calprotectin to serve as a surrogate biomarker of IBD activity and outlined a framework for further validation and development of biomarkers. No endpoints have been fully validated as surrogates of risk of disease complications; mucosal healing is the most valid endpoint used to determine risk of disease complications. Fecal level of calprotectin has not been validated as a biomarker for IBD activity because of lack of technical and clinical reliability, assessment of performance when used as a replacement forendoscopy, and assessment of responsiveness to changes in disease states. The level of fecal calprotectin can be usedonly as a prognostic factor for disease recurrence in patients inremission after medical or surgical treatment. We reviewed guidelines, regulatory documents, and publications to identify properties required forthe development of biomarkers of IBD activity and areas in need of clarification from regulatory agencies and societies. We propose a path forward for research of biomarkers for IBD.

A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection.

Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined. We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA-mRNA target network was generated and analyzed. For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98-9.88, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40-12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50-6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65-6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88-13.92, P < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001). The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.See related commentary by Clump et al., p. 1441.

Lymphatic Mapping and Sentinel Node Biopsy

With an estimated 232,670 new cases in the United States in 2014, breast cancer is among the most common malignancies treated by US surgeons. Meanwhile, the incidence of melanoma is rising faster than for all other solid malignancies, with an estimated 76,100 new cases of invasive melanoma in the United States in 2014. Over the past 20 years, significant strides have been made in the management of these two diseases from the standpoint of both surgical and adjuvant therapy. For both diseases, the presence or absence of lymph node metastases is highly predictive of patient outcome and is the most important prognostic factor for disease recurrence and cancer-related mortality. This review covers lymphatic mapping and sentinel node biopsy for melanoma, special circumstances associated with sentinel node biopsy in melanoma, lymphatic mapping and sentinel node biopsy in breast cancer, and radiation exposure guidelines and policies. The figures show lymphatic mapping and sentinel lymph node biopsy for melanoma, lymphatic mapping and sentinel node biopsy for breast cancer, and touch-imprint cytology from lymphatic mapping and sentinel node biopsy for breast cancer. This review contains 3 highly rendered figures and 89 references.

A systematic review and meta‐analysis of the impact of lymphovascular invasion in bladder cancer transurethral resection specimens

The aim of the present review was to assess the prognostic impact of lymphovascular invasion (LVI) in transurethral resection (TUR) of bladder cancer (BCa) specimens on clinical outcomes. A systematic review and meta‐analysis of the available literature from the past 10 years was performed using MEDLINE, EMBASE and Cochrane library in August 2017. The protocol for this systematic review was registered on PROSPERO (Central Registration Depository: CRD42018084876) and is available in full on the University of York website. Overall, 33 studies (including 6194 patients) evaluating the presence of LVI at TUR were retrieved. LVI was detected in 17.3% of TUR specimens. In 19 studies, including 2941 patients with ≤cT1 stage only, LVI was detected in 15% of specimens. In patients with ≤cT1 stage, LVI at TUR of the bladder tumour (TURBT) was a significant prognostic factor for disease recurrence (pooled hazard ratio [HR] 1.97, 95% CI: 1.47–2.62) and progression (pooled HR 2.95, 95% CI: 2.11–4.13), without heterogeneity (I 2 = 0.0%, P = 0.84 and I 2 = 0.0%, P = 0.93, respectively). For patients with cT1–2 disease, LVI was significantly associated with upstaging at time of radical cystectomy (pooled odds ratio 2.39, 95% CI: 1.45–3.96), with heterogeneity among studies (I 2 = 53.6%, P = 0.044). LVI at TURBT is a robust prognostic factor of disease recurrence and progression in non‐muscle invasive BCa. Furthermore, LVI has a strong impact on upstaging in patients with organ‐confined disease. The assessment of LVI should be standardized, reported, and considered for inclusion in the TNM classification system, helping clinicians in decision‐making and patient counselling.