Significant Difference In Disease-specific Survival Research Articles

External Validation of the New International Association for the Study of Lung Cancer Tumor, Node, and Metastasis 8th Edition Staging System and Updated T Descriptors in Determining Prognosis for Patients With Non–Small Cell Lung Cancer Patients With N3 Disease

ObjectiveThe objective of this study is to externally validate the 8th Edition of the Tumor, Node, and Metastasis staging system and its updated T descriptors in patients with non–small cell lung cancer with N3 disease. MethodsData were extracted from the Surveillance, Epidemiology, and End Results database. Chi-square test, Kaplan–Meier method, and Cox regression models were used in SPSS 23.0 (IBM Corp, Armonk, NY). ResultsA total of 7732 patients with non–small cell lung cancer with T1-4N3M0 disease from 1988 to 2013 were identified. A total of 1410 patients (18.2%) had T1N3 disease, 2491 patients (32.2%) had T2N3 disease, 1563 patients (20.2%) had T3N3 disease, and 2268 patients (29.3%) had T4N3 disease. The 5-year overall survival (OS) for the entire cohort was 8.4%. There was a significant difference in OS concerning T stage (T1N3: 10.8% vs. T2N3: 8.3% vs. T3N3: 8.1% vs. T4N3: 7.3%; P < .001). When stratified by the median age of patients (66 years), a significant difference in OS by stage of disease (IIIB vs. IIIC) was still observed in both the younger (P < .001) and older (P < .001) patient populations. A significant difference in disease-specific survival (DSS) was observed by T stage (T1N3: 14.7% vs. T2N3: 11.6% vs. T3N3: 11.3% vs. T4N3: 9.7%; P < .001). On multivariate analysis, T stage, year of diagnosis, age, gender, histology, and receipt of radiotherapy remained independent prognostic factors for both OS and DSS. ConclusionsThe 8th Edition of the Tumor, Node, and Metastasis staging system significantly stratifies both overall and DSS between stages IIIB and IIIC among those with N3 disease. However, small absolute differences in 5-year outcomes between T stage may suggest limited clinical relevance.

Incidence and survival differences in esophageal cancer among ethnic groups in the United States.

ObjectivesThis study was performed to identify the differences in incidence, clinicopathological features, and survival in esophageal cancer among ethnic groups in the United States and to determine the reasons for the differences.ResultA total of 49,766 patients were included. Black and Asian groups had a higher proportion of squamous cell carcinoma (ESCC) (85.5% and 75.4%, respectively) and mid-esophagus tumor (43.2% and 37.7% respectively) than the non-Hispanic white and Hispanic white groups. The incidences of ESCC in all ethnic groups declined since 1973, especially in black males. At the same time, incidences of esophageal adenocarcinoma (EAC) dramatically increased in white males since 1973. And incidences of ESCC and EAC were the lowest and stable in Asian female. Multivariable models showed that patients who were male, or black, or had larger tumors, or positive lymph nodes had an increased risk of death from esophageal cancer, while patients with ESCC or diagnosed after 2005 or treated with surgery had a lower likelihood of death. For ESCC, the black patients had the lowest DSS, while for EAC there were no significant differences in DSS among the ethnic/racial groups.Materials and MethodFrom the Surveillance, Epidemiology, and End Results Program database, patients diagnosed with esophageal cancer from 1998-2013 were identified. Differences in incidences, clinicopathological features, treatments, and disease-specific survival (DSS) in four broad racial/ethnic groups were compared.ConclusionHistological type distribution between racial groups could be an important consideration in the incidence and the survival trend but other factors could also have an effect.

Relationship between response to induction chemotherapy and disease control in patients with advanced laryngeal carcinoma included in an organ preservation protocol.

The aim of the study is to analyze the relationship between the degree of response to induction chemotherapy and the disease control in patients with locally advanced laryngeal carcinomas candidates to total laryngectomy. This retrospective study includes 389 patients with T3-T4 laryngeal tumors candidates to total laryngectomy, diagnosed between 1985 and 2013, treated with induction chemotherapy in an organ preservation protocol. Five-year local recurrence-free survival for patients receiving conservative treatment with radiotherapy after a complete response to induction chemotherapy was 75.4%; for patients with partial response greater than 50%, it was 62.0%; and for patients with the absence of response, it was 32.7%. There were significant differences in local recurrence-free survival and laryngeal dysfunction-free survival according to the response to induction chemotherapy (P = 0.0001) at the expense of patients with absence of response to induction chemotherapy. Patients with partial response greater than 50% treated with radiotherapy had a tendency to have worse local recurrence-free survival and laryngeal dysfunction-free survival than patients with complete response, but the differences did not reach statistical significance. Patients with the absence of response after induction chemotherapy had significant differences in disease-specific survival according to the second treatment: for patients treated with surgery it was 70.2%, whereas for patients treated with radiotherapy, it was 28.2% (P = 0.0001). In patients with the absence of response to induction chemotherapy, conservative treatment with radiotherapy implies a significant decrease in survival.

Survival Trends in Young Patients with Waldenstrom Macroglobulinemia: Over 5 Decades of Experience

BackgroundWaldenstrom macroglobulinemia (WM) is an IgM-associated lymphoplasmacytic lymphoma, first described over seven decades ago. Although WM is typically a disease of the elderly, with a median age at diagnosis of ~ 67 years, approximately 10% of patients are ≤50 years (y) of age at diagnosis. Data for young patients are sparse and the few available studies demonstrate inconsistent findings, with potential overestimation of survival owing to inclusion of patients with smoldering WM. In this case-control study, we evaluate outcomes, prognostic features and impact of changing therapies in a large cohort of young symptomatic WM patients compared to matched older patients seen over the course of the past five decades.MethodsThe medical records of all WM patients seen consecutively at Mayo Clinic from 01/1960 to 10/2013 were reviewed. Of 1181 patients, 140 (11.8%) were ≤ 50 y of age at diagnosis. A cohort of patients 65 y or older at diagnosis, matched 1:1 by the time of diagnosis, served as the control population. The patients were divided into 3 groups based on the timing of initiation of therapy: Group 1 (1960-1977), Group 2 (1978-1995) and Group 3 (1996-2013). The baseline characteristics were compared. Initiation of frontline therapy was used for all time-to-event analysis using the Kaplan Meier method.ResultsYounger patients were more likely to present with adenopathy and splenomegaly, have higher IgM levels and hyperviscosity symptoms (Table 1). The median follow-up from the frontline therapy was similar (10.7 y vs. 10 y for the control population). At the time of analysis, 91% of the deaths for the younger cases were WM-related compared to 58% in the control arm (p=0.0001). Younger patients had a better OS with a median disease-specific survival (DSS) of 15.6 y (95% CI: 13-21; 10-y OS of 77%) vs. 11 y (95% CI: 7.8-12; 10-y OS of 51%) for the older patient (p=0.0003).Among the young patients, there was no difference in the median DSS across the 3 groups (p=0.42). However, the median DSS for the control group incrementally improved (p=0.02) over the 3 time periods (Table 1).In the younger patients, no improvement in DSS was noted with the use of either frontline rituximab-based therapy compared to non-rituximab based regimens [median NR (95% CI: 7.6-NR) vs. 15.8 y (95% CI: 13-22) with other regimens, p=0.30], or frontline chlorambucil-based compared to non-chlorambucil based regimens [median 16 y (95% CI: 12-22) vs 15.6 y (95% CI: 12-NR) with other regimens, p=0.73]. In the control group, however, there was significant difference in DSS among patients who received frontline rituximab-based compared to non-rituximab based regimens [median NR (95% CI: 8.3-NR) vs 9.1 y (95% CI: 5.6-12) with other regimens, p=0.04], or frontline chlorambucil-based vs non-chlorambucil based regimens [8 y (95% CI: 5-12) vs 12.3 y (95% CI: 11-NR) in other regimens; p=0.001].ConclusionStriking differences in presentation are evident in young WM patients compared to their older counterparts. The incorporation of rituximab to the previously existing anti-WM regimens and the transition to non-chlorambucil based regimens has resulted in substantial survival gains in the older WM population over the past five decades. However, such improvement in outcome has not yet been observed in the young patients. The majority of younger patients, despite a protracted disease course, succumb to their disease. [Display omitted] DisclosuresAnsell:BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding. Ailawadhi:Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy. Reeder:Novartis: Research Funding; Celgene: Research Funding; BMS: Research Funding; Millennium: Research Funding. Kumar:Kesios: Consultancy; Janssen: Consultancy, Research Funding; Sanofi: Consultancy, Research Funding; AbbVie: Research Funding; BMS: Consultancy; Onyx: Consultancy, Research Funding; Glycomimetics: Consultancy; Millennium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Noxxon Pharma: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Skyline: Honoraria, Membership on an entity's Board of Directors or advisory committees. Dispenzieri:Alnylam: Research Funding; Celgene: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Prothena: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; pfizer: Research Funding; Jannsen: Research Funding. Kapoor:Celgene: Research Funding; Takeda: Research Funding; Amgen: Research Funding.

MLH1-deficient Colorectal Carcinoma With Wild-type BRAF and MLH1 Promoter Hypermethylation Harbor KRAS Mutations and Arise From Conventional Adenomas.

Between 10% and 15% of colorectal carcinomas demonstrate sporadic DNA mismatch-repair protein deficiency as a result of MLH1 promoter methylation and are thought to arise from sessile serrated adenomas, termed the serrated neoplasia pathway. Although the presence of the BRAF V600E mutation is indicative of a sporadic cancer, up to 30% to 50% of colorectal carcinomas with MLH1 promoter hypermethylation will lack a BRAF mutation. We report the clinicopathologic and molecular features of MLH1-deficient colorectal carcinoma with wild-type BRAF and MLH1 promoter hypermethylation (referred to as MLH1-hypermethylated BRAF wild-type colorectal carcinoma, n=36) in comparison with MLH1-deficient BRAF-mutated colorectal carcinoma (n=113) and Lynch syndrome-associated colorectal carcinoma (n=36). KRAS mutations were identified in 31% of MLH1-hypermethylated BRAF wild-type colorectal carcinomas compared with 0% of MLH1-deficient BRAF-mutated colorectal carcinomas and 37% of Lynch syndrome-associated colorectal carcinomas. When a precursor polyp was identified, MLH1-hypermethylated BRAF wild-type colorectal carcinomas arose from precursor polyps resembling conventional tubular/tubulovillous adenomas in contrast to MLH1-deficient BRAF-mutated colorectal carcinomas, which arose from precursor sessile serrated adenomas (P<0.001). Both MLH1-hypermethylated BRAF wild-type colorectal carcinoma and MLH1-deficient BRAF-mutated colorectal carcinoma had a predilection for the right colon compared with Lynch syndrome-associated colorectal carcinoma (86% vs. 92% vs. 49%, P<0.001). There was no significant difference in mucinous differentiation, tumor-infiltrating lymphocytes, Crohn-like reaction, and medullary differentiation between the 3 tumor groups. Using Kaplan-Meier survival functions, there was no significant difference in disease-specific survival between the 3 patient groups (P>0.05). In conclusion, our results indicate that MLH1-hypermethylated BRAF wild-type colorectal carcinomas can harbor KRAS mutations and arise from precursor polyps resembling conventional tubular/tubulovillous adenomas.

Changes in oncological outcomes after radical nephroureterectomy in patients with upper urinary tract urothelial carcinoma treated in the last two decades: a retrospective analysis based on a multicenter collaborative study.

We investigated chronological changes in the outcomes of patients with upper urinary tract urothelial carcinomatreated in the past two decades, during which there was an important change in treatment paradigm. A retrospective review was conducted of 1180 urinary tract urothelial carcinoma patients who underwent radical nephroureterectomy in multicenter collaborative institutions between 1996 and 2015. The patients were divided into four groups according to the year when radical nephroureterectomy was performed, as follows: 1996-2000 (period 1; P1), 2001-05 (P2), 2006-10 (P3) and 2011-15 (P4). Variables including tumor grade, T and N categories, administration of perioperative chemotherapy and treatment outcomes were compared among the four groups. There were 146 (12%), 312 (27%), 459 (39%) and 263 (22%) patients in the P1, P2, P3 and P4 groups, respectively. The proportion of patients harboring pT2/3 and Grade 3 tumors increased gradually from 42% (P1) to 58% (P4) and from 49% (P1) to 65% (P4), respectively. The 5-year disease-free survival rates were 74%, 74%, 73% and 75%, and the 5-year overall survival rates were 74%, 65%, 67% and 72% for the P1, P2, P3, and P4 groups, respectively. Multivariate analysis with adjustment for possible confounding factors revealed no significant differences in disease-specific survival, overall survival or intravesical recurrence-free survival among the four groups. Despite advances in diagnostic instruments, surgery and systemic chemotherapy, the clinical outcome of urinary tract urothelial carcinoma after radical surgery has not significantly improved over the last two decades, and further research is therefore required.

The prognostic value of pretreatment platelet count in patients with head and neck squamous cell carcinoma

Thrombocytosis is commonly observed in patients with solid tumors. This study aimed to evaluate the prognostic role of circulating pretreatment platelet count in a large series of patients with head and neck squamous cell carcinoma (HNSCC). We retrospectively studied 824 patients with HNSCC treated at a single institution from 2000 to 2012. Disease-specific survival and local, regional, and distant recurrence-free survival were analyzed according to the distribution of the platelet count. By defining the platelet count 250.05×109/L as a cut-off point with the best predictive capacity, we classified the patients into two groups: those with a high platelet count (n=378, 45.9%), and those with a low platelet count (n=446, 54.1%). On univariate analysis, there were significant differences in disease-specific survival depending on pretreatment platelet count (P=0.001). The 5-year specific survival rates were 74.1% (CI 95%: 69.8-78.4%) and 61.6% (CI 95%: 56.4-66.8%) for patients with a low and high platelet count, respectively. According to the results of a multivariate analysis, patients with a high count of platelets had a tendency to a lower disease-specific survival, but the hazard ratio did not reach statistically significant differences (HR 1.24, CI 95%: 0.97-1.61, P=0.085). Platelet count was significantly associated with survival in univariate analysis. However, in a multivariate analysis it lost its prognostic capacity, limiting its utility as a prognostic marker in patients with HNSCC. Considering separately each primary tumor location, patients with hypopharyngeal cancer and a high platelet count had a significant decrease of disease-specific survival.

Role of major resection in pulmonary metastasectomy for colorectal cancer in the Spanish prospective multicenter study (GECMP-CCR)

Patients with pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. The objective of this study was to determine the role of major anatomic resection for pulmonary metastasectomy to improve survival when compared with limited pulmonary resection. Data of 522 patients (64.2% men, mean age 64.5 years) who underwent pulmonary resections with curative intent for CRC metastases over a 2-year period were reviewed. All patients were followed for a minimum of 3 years. Disease-specific survival (DSS) and disease-free survival (DFS) were assessed with the Kaplan-Meier method. Factors associated with DSS and DFS were analyzed using a Cox proportional hazards regression model. A total of 394 (75.6%) patients underwent wedge resection, 19 (3.6%) anatomic segmentectomy, 5 (0.9%) lesser resections not described, 100 (19.3%) lobectomy, and 4 (0.8%) pneumonectomy. Accordingly, 104 (19.9%) patients were treated with major anatomic resection and 418 (80.1%) with lesser resection. Operations were carried out with video-assisted thoracoscopic surgery (VATS) in 93 patients. The overall DSS and DFS were 55 and 28.3 months, respectively. Significant differences in DSS and DFS in favor of major resection versus lesser resection (DSS median not reached versus 52.2 months, P = 0.03; DFS median not reached versus 23.9 months, P < 0.001) were found. In the multivariate analysis, major resection appeared to be a protective factor in DSS [hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.41-0.96, P = 0.031] and DFS (HR 0.5, 95% CI 0.36-0.75, P < 0.001). The surgical approach (VATS versus open surgical resection) had no effect on outcome. Major anatomic resection with lymphadenectomy for pulmonary metastasectomy can be considered in selected CRC patient with sufficient functional reserve to improve the DSS and DFS. Further prospective randomized studies are needed to confirm the present results.

Impact of multidisciplinary bladder cancer care for muscle invasive bladder cancer: A propensity score matched analysis of survival outcomes.

455 Background: We started in 2008 a Multidisciplinary Bladder Cancer Clinic (MDBCC), where complex bladder cancer patients are assessed concurrently by urologic and radiation oncologists, with support from medical oncologists. Patients have the opportunity to discuss various treatment options including radical cystectomy (RC) or bladder sparing trimodal therapy (TMT; endoscopic resection, radiotherapy and chemotherapy). Although reports have shown comparable outcomes of TMT to cystectomy, no direct comparison to RC has been published and no randomized studies are available. We report our long term outcomes of multidisciplinary care, comparing TMT to surgery using propensity-matched analyses. Methods: Patients seen in our MDBCC receiving TMT for MIBC from 2008 to 2012 were identified and matched, using propensity scores, to patients operated by RC. Matching occurred on age, ECOG status, Charlson comorbidity score, cT stage, cN stage and date of treatment. Overall survival (OS) and disease-specific survival (DSS) were assessed with Cox Proportional hazards modeling and competing risk analysis, respectively. Results: Between 2008 and 2012, 248 patients were assessed in the MDBCC. Of these, 162 (65%) had MIBC. Nearly half (80) opted for radiotherapy +/- concurrent cisplatin chemotherapy and 49 underwent full bladder preservation with TMT as their primary therapy. We matched 48 TMT patients with 48 RC patients with no imbalances. Median age of the cohort was 67.5 years with 29.2% cT3/cT4. With a median follow up time of 3.62 years, there were 19 (39.6%) deaths (7 from bladder cancer) in the RC group and 15 (31.3%) deaths (6 from bladder cancer) in the TMT group. 5 year DSS was 85.2% and 84.7% with TMT and surgery, respectively (p &gt; 0.05). There was no statistically significant difference in DSS between the two groups (HR for TMT 1.31 (0.40-4.23), p = 0.66) or in OS (HR for TMT 0.77 (0.34-1.75), p = 0.53). Conclusions: Bladder cancer patients benefit from a multidisciplinary approach.. In selected patients with MIBC, chemo-radiation yields survival outcomes similar to matched RC patients. BC patients should be offered the possibility to discuss various treatment options.

Conditional Survival in de novo Metastatic Urothelial Carcinoma.

BackgroundSecond-line therapy is frequently utilized for metastatic urothelial carcinoma, but there are limited data to guide this approach. While an assessment of overall survival based on registry data may not capture the impact of second- and third-line therapies on clinical outcome, this may be reflected in relative conditional survival (RCS).MethodsPatients with stage IV urothelial carcinoma diagnosed from 1990–2010 were identified from the Surveillance, Epidemiology and End Results (SEER) dataset. The association of clinicopathologic variables with disease specific survival (DSS) was explored through univariate and multivariate analyses. DSS in subgroups divided by time period (1990–2000 v 2001–2010) was compared using the Kaplan-Meier method and log-rank test. One-year RCS at annual landmarks up to 5 years was compared in subgroups divided by time period.ResultsOf 261,987 patients diagnosed with urothelial carcinoma from 1990–2010, 3,110 patients met criteria for the current analysis. Characteristics of patients diagnosed between 1990 and 2000 (n = 810) and 2001 to 2010 (n = 2,300) were similar and there was no significant difference in DSS between the two groups. On multivariate analysis, older age (age ≥ 80) was associated with shorter DSS (HR 1.79, 95%CI 1.48–2.15), but no association was found between time period of diagnosis and outcome. One-year RCS improved substantially through successive annual landmarks up to 5 years, but no differences were seen in subgroups divided by time of diagnosis.ConclusionsNo difference in RCS was observed amongst patients with stage IV urothelial carcinoma diagnosed from 1990–2000 and 2001–2010. A lack of difference in RCS (more so than cumulative DSS) may reflect a lack of progress in salvage therapies for the disease.

Clinicopathological Characteristics and Survival Outcomes of Invasive Cribriform Carcinoma of Breast: A SEER Population-Based Study.

Invasive cribriform carcinoma (ICC) is a rare histologic subtype of breast cancer. We aimed to investigate the clinicopathological characteristics and survival outcomes of ICC.Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 233,337 female patients diagnosed with ICC (n = 618) or infiltrating ductal carcinoma (IDC) (n = 232,719). Univariate and multivariate survival analyses were utilized to calculate and compare disease-specific survival (DSS) and overall survival (OS). A 1:1 paired match was carried out on age, tumor stage, tumor grade, estrogen receptor (ER) status, and progesterone receptor (PR) status. Baseline characteristics and survival outcomes were also analyzed in ER-positive tumors. Subgroup analyses summarized the hazard ratio (HR) of IDC versus ICC using a forest plot.ICCs presented smaller size, lower grade, higher ER and PR positive rate, less nodal metastasis, and were less likely to be treated with mastectomy compared to IDCs. Five-year DSS rates were significantly better for patients with ICC than for patients with IDC (98.8% vs. 93%, P < 0.001). Five-year OS rates were 95.3% versus 90.1% (P < 0.001). After adjustment for common clinicopathological factors in the multivariate analysis, patients with ICC showed limited DSS advantage over the IDC group (HR = 0.75, 95% CI: 0.38-1.51, P = 0.421). No significant difference in DSS nor OS was observed in matched groups between ICC and IDC. Analysis among ER-positive patients revealed similar prognostic factors as among all patients. Survival analysis in different tumor grade subgroups showed no significant difference between ICC and IDC.ICCs have unique clinicopathological characteristics, higher rates of breast-conserving surgery, and more favorable prognosis compared to the overall IDC population. Difference in tumor grade between the 2 groups may partially explain the different outcome. Improved clinical and biological understanding of ICC might lead to more individualized and tailored therapy for breast cancer patients.

The effect of smoking on prostate cancer survival: a cohort analysis in Barcelona.

The aim of this study was to analyse the effect of smoking on prostate cancer-specific mortality and all-cause mortality. A retrospective cohort study was conducted with 1109 patients with prostate cancer diagnosed from 1992 to 2008, identified through the Hospital del Mar Cancer Registry (Barcelona, Spain). Information on smoking habits was retrieved from clinical records and patients were classified into three categories: never smoker, exsmoker and current smoker. Patients were followed up until December 2011. Survival curves were plotted using Kaplan-Meier methods. Cox models were used to estimate hazard ratios and 95% confidence intervals. Median age at diagnosis was 70.6 years and 16.7% of patients had stage IV tumours. During the follow-up period, 466 deaths occurred, 36.1% of them being specifically due to prostate cancer. The median follow-up time of the censored patients was 5.8 years. There was a significant difference in disease-specific survival between never smokers, exsmokers and current smokers (P=0.0001). Current smokers presented a worse 5-year survival rate (82.9%) compared with exsmokers (88.9%) and never smokers (89.6%). In the multivariate analysis, after adjusting for age, disease stage, Gleason score and prostate-specific antigen, the hazard ratio for smokers was 1.80 (95% confidence interval: 1.04-3.13) compared with never smokers. In the exsmokers group the risk for prostate cancer-specific mortality was very similar to that of never smokers. However, the statistical difference disappeared when we stratified by stage (I-III and IV). In conclusion, smoking was identified as an independent and negative prognostic factor for prostate cancer-specific and all-cause mortality. These findings suggest that smoking-cessation programmes could be beneficial for prostate cancer patients.

Sentinel lymph node biopsy followed by lymph node dissection for localised primary cutaneous melanoma.

Sentinel lymph node biopsy followed by lymph node dissection for localised primary cutaneous melanoma.

Abstract P6-08-24: Age independently predicts worse disease-specific survival in patients diagnosed with invasive breast cancers at 50 years of age or older but not younger

Abstract BACKGROUND It has been reported that women diagnosed with invasive breast cancer (IBC) in their 50s or 60s have better survival than either younger or older women. Young women with IBCs often have a more aggressive phenotype which contributes to worse survival. But there is supporting evidence in the literature for both sides whether age alone is an intrinsic driver of the poor outcome in young women. The availability of large-scale IBC data provided a good opportunity to address this issue. METHODS Clinicopathologic and gene expression data from 2 public datasets, including METABRIC from the European Genome-Phenome Archive (n=1992) and The Cancer Genome Atlas-Breast Cancer project (TCGA-BC, n=980) from National Cancer Institute, were used in this study. PAM50 was used to derive intrinsic subtypes based on microarray and RNA-Seq data. For a given phenotype, Fisher’s exact test was used for its association with age, and 2-sample test for equality of proportions with continuity correction between young and older patients. Kolmogorov-Smirnov’s test was used for equality of age distributions between phenotypes. Disease-specific survival (DSS) was examined for relationship with age, adjusted for race, AJCC stage, nodal metastasis, tumor size, grade, and subtype where applicable. Kaplan-Meier estimate and log-rank test were used to generate and compare survival curves, respectively. Cox proportional hazards model was used for univariate and multivariate analyses and to calculate hazard ratios (HRs). RESULTS Firstly, we confirmed that more aggressive IBCs were enriched in young patients. Younger patients (&amp;lt;50 years) were diagnosed with more basal-like subtype (P&amp;lt;0.05) and more node+ diseases (P&amp;lt;0.05) compared with their older counterparts (≥50 years) in both datasets. Secondly, we found no significant difference in DSS between these 2 age groups after adjusting for subtype and other clinicopathologic variables. Finally, we examined the effect of age on DSS within the young and older patient groups separately. In the young patient group, age was not predictive of DSS in multivariate models in either datasets. However, in the older patient group, after adjusting for the effects of other clinicopathologic variables in the METABRIC dataset, the continuously increasing age was associated with worse DSS in all subtypes (HR=1.018, P=0.0076), as well as Luminal A (HR=1.041, P=0.00074) and Luminal B (HR=1.021, P=0.047) but not HER2+ or basal-like subtype in this age group. The results were validated in the TCGA-BC data (HR=1.055 and P=0.0052 in all older patients; HR=1.070 and P=0.066 in Luminal A; HR=1.081 and P=0.034 in Luminal B). CONCLUSION Our results supported that age was not an independent predictor of DSS for patients diagnosed at age &amp;lt;50 years, and the worse outcome of this age group was apparently a surrogate for more aggressive IBC phenotype. Our observation that age was an independent predictor of worse DSS in the older patient group, especially patients with Luminal A and B but not the other subtypes, warrants further molecular studies. The views expressed in this abstract are those of the authors and do not reflect the official policy of the Department of Defense, or U.S. Government. Citation Format: Yuanbin Ru, Richard J Mural, Patricia S Steeg, Hallgeir Rui, Craig D Shriver, Hai Hu. Age independently predicts worse disease-specific survival in patients diagnosed with invasive breast cancers at 50 years of age or older but not younger [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-08-24.

Association of sentinel lymph node biopsy with survival for head and neck melanoma: survival analysis using the SEER database.

Sentinel lymph node biopsy (SLNB) provides prognostic information for melanoma; however, a survival benefit has not been demonstrated. To assess the association of SLNB with survival for melanoma arising in head and neck subsites (HNM). Propensity score-matched retrospective cohort study using the Surveillance Epidemiology and End Results (SEER) database to compare US patients with HNM meeting current recommendations for SLNB, treated from 2004 to 2011 with either (1) SLNB with or without neck dissection, or (2) no SLNB or neck dissection. SLNB with or without neck dissection. Disease-specific survival (DSS) estimates based on the Kaplan-Meier method, and Cox proportional hazards modeling to compare survival outcomes between matched pair cohorts. A total of 7266 patients with HNM meeting study criteria were identified from the SEER database. Matching of treatment cohorts was performed using propensity scores modeled on 10 covariates known to be associated with SLNB treatment or melanoma survival. Cohorts were stratified by tumor thickness (thin, >0.75-1.00 mm Breslow thickness; intermediate, >1.00-4.00 mm; and thick, >4.00 mm) and exactly matched within 5 age categories. In the intermediate-thickness cohort, 2808 patients with HNM were matched and balanced by propensity score for SLNB treatment; the 5-year DSS estimate for those treated by SLNB was 89% vs 88% for nodal observation (log-rank P = .30). The hazard ratio for melanoma-specific death was 0.87 for those undergoing SLNB (95% CI, 0.66-1.14; P = .31). In each of the other cohorts analyzed, including those with thin and thick melanomas, and cohorts with melanoma overall, no significant difference in DSS was demonstrated. This SEER cohort analysis demonstrates no significant association between SLNB and improved disease-specific survival for patients with HNM.

Epstein-Barr virus and human papillomavirus infections and genotype distribution in head and neck cancers.

ObjectiveTo investigate the prevalence, genotypes, and prognostic values of Epstein-Barr virus (EBV) and human papillomavirus (HPV) infections in Japanese patients with different types of head and neck cancer (HNC).Methods and MaterialsHPV and EBV DNA, EBV genotypes and LMP-1 variants, and HPV mRNA expression were detected by PCR from fresh-frozen HNC samples. HPV genotypes were determined by direct sequencing, and EBV encoded RNA (EBER) was examined by in situ hybridization.ResultsOf the 209 HNC patients, 63 (30.1%) had HPV infection, and HPV-16 was the most common subtype (86.9%). HPV E6/E7 mRNA expression was found in 23 of 60 (38.3%) HPV DNA-positive cases detected. The site of highest prevalence of HPV was the oropharynx (45.9%). Among 146 (69.9%) HNCs in which EBV DNA was identified, 107 (73.3%) and 27 (18.5%) contained types A and B, respectively, and 124 (84.9%) showed the existence of del-LMP-1. However, only 13 (6.2%) HNCs were positive for EBER, 12 (92.3%) of which derived from the nasopharynx. Co-infection of HPV and EBER was found in only 1.0% of HNCs and 10.0% of NPCs. Kaplan-Meier survival analysis showed significantly better disease-specific and overall survival in the HPV DNA+/mRNA+ oropharyngeal squamous cell carcinoma (OPC) patients than in the other OPC patients (P = 0.027 and 0.017, respectively). Multivariate analysis showed that stage T1–3 (P = 0.002) and HPV mRNA-positive status (P = 0.061) independently predicted better disease-specific survival. No significant difference in disease-specific survival was found between the EBER-positive and -negative NPC patients (P = 0.155).ConclusionsOur findings indicate that co-infection with HPV and EBV is rare in HNC. Oropharyngeal SCC with active HPV infection was related to a highly favorable outcome, while EBV status was not prognostic in the NPC cohort.

High-risk HPV and survival in patients with oral and oropharyngeal squamous cell carcinoma – 5-year follow up of a population-based study

Conclusion: No statistically significant 5-year survival difference was seen in patients with oral and oropharyngeal squamous cell carcinoma (OOPSCC) between high-risk HPV-positive and -negative groups in this population-based study. Objectives: To see if the formerly observed higher risk for recurrence or second primary tumour (SPT) in high-risk HPV-positive patients with OOPSCC corresponds to worse survival. Methods: A total of 128 consecutive, previously untreated patients with OOPSCC, who were part of a population-based case-control study in southern Sweden during 2000–2004, were included. A mouthwash sample was collected and exfoliated cells were collected with cotton-tipped swabs from the tonsillar fossa and the tumour. Specimens were analysed for HPV DNA using nested polymerase chain reaction (PCR). Disease-specific survival (DSS) and DSS difference between HPV-negative and HPV-positive patients were calculated. The relationship between age, stage, high-risk HPV status and DSS was assessed. Oral and oropharyngeal tumours were assessed separately. Results: Mean DSS in months was 80.7/68.6 (high-risk HPV-negative/high-risk HPV-positive) for oral cavity tumours (p = 0.18) and 67.6/78.3 (high-risk HPV-negative/high-risk HPV-positive) for oropharyngeal tumours (p = 0.47). For oral cavity tumours, age, T status, N status and stage all showed significant differences in DSS. For oropharyngeal tumours, no significant difference regarding DSS was found.

Alpha B-crystallin – a validated prognostic factor for poor prognosis in squamous cell carcinoma of the oral cavity

Conclusion: Alpha B-crystallin was found to be an independent prognostic marker for poor prognosis in oral cavity tumours. For oropharyngeal cancer, alpha B-crystallin had no prognostic value. Objective: The aim of this study was to see if earlier findings of alpha B-crystallin as an independent prognostic marker, and SPARC/osteonectin, PAI-1 and uPA as a prognostic combination for poor outcome in squamous cell carcinoma (SCC) of the head and neck could be confirmed in a new set of tumours. Methods: In a consecutive series of patients, assessed and primarily treated at a tertiary referral centre, histological sections from 55 patients with oral and SCC (OOPHSSC) with complete clinical data and follow-up were obtained. Oral and oropharyngeal tumours were studied separately. Immunohistochemical detection of alpha B-crystallin, SPARC/osteonectin, PAI-1 and uPA expression was performed. Results: Thirty-five patients had an oral tumour and 20 patients an oropharyngeal tumour. Twenty-five oral tumours stained negatively and 10 positively for alpha B-crystallin. For oropharyngeal tumours the figures were 15 negatively and 5 positively. Median disease-specific survival (DSS) for both sites was 33.8 and 11.9 months, for negative and positive alpha B-crystallin staining, respectively (p = 0.046). For the oral cavity, median DSS was 27.3 months for negative tumours and 7.5 months for positive tumours (p = 0.012). Corresponding figures for oropharyngeal tumours were 33.8 and 34.1 months (p = 0.95). Thus, significance in survival was only found in oral cavity tumours. In multivariate analyses there were no significant differences in DSS in the oropharyngeal group when adjusted for tumour size (T status) and presence of neck node metastasis (N status). In the oral cavity group, the significantly better DSS for negative tumours became even stronger when adjusted for T and N status. No statistical difference was found in DSS between positive and negative staining for SPARC/osteonectin, PAI-1 or uPA.

Case‐control analysis of survival outcomes in sinonasal acinic cell carcinoma

Acinic cell carcinoma (AciCC) is an uncommon malignant-epithelial salivary gland cancer. In very rare cases, this tumor may arise from sinonasal subsites, with only 19 cases described in the English-language literature. We performed a retrospective analysis of 18 cases of AciCC, obtained from searching the Surveillance, Epidemiology, and End Results (SEER) database between 1973 and 2009. Patient demographics, including age, gender, and race, were similar to AciCC cases found in more common locations. However, all patients had low-grade tumors without regional or distant metastases. Comparing these patients to a stage, grade, and treatment-matched cohort of parotid AciCC, we found a lower 10-year overall survival (52.3%) with no significant difference in disease-specific survival (88.9%). Our meta-analysis of survival from cases in the literature estimated 10-year recurrence-free survival at 92.9%. To our knowledge, this is the largest cohort of patients with AciCC reported in the English-language literature. Our results suggest that patients with sinonasal AciCC have excellent disease-specific survival, comparable to matched patients with AciCC in more common salivary gland subsites.

Patterns of nodal metastasis and prognosis in human papillomavirus-positive oropharyngeal squamous cell carcinoma.

The current American Joint Committee on Cancer (AJCC) staging system may not accurately reflect survival in patients with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (SCC). The purpose of this study was to develop a system that more precisely predicts survival. CT scans from 156 patients who underwent chemoradiation for advanced-stage oropharyngeal SCC with >2 years follow-up were reviewed. We modeled patterns of nodal metastasis associated with different survival rates. We defined HPV+ N1 as a single node <6 cm, ipsilaterally, contralaterally, or bilaterally. HPV+ N2 was defined as a single node ≥6 cm or ≥2 nodes ipsilaterally/contralaterally or ≥3 nodes bilaterally. HPV+ N3 was defined as matted nodes. There was no significant difference in disease-specific survival (DSS; p = .14) or overall survival (OS; p = .16) by AJCC classification. In patients grouped by HPV+ N1, HPV+ N2, and HPV+ N3 nodal classification, significant differences in DSS (100%, 92%, and 55%, respectively; p = .0001) and OS (100%, 96%, and 55%, respectively; p = .0001) were found. A staging system with reclassification of size, bilaterality, and matted nodes more accurately reflects survival differences in this cohort of patients. Review of the AJCC staging system with these criteria should be considered for HPV-positive oropharyngeal SCC.