Better Survival In Stage Research Articles

Lung Cancer in Young Patients is Associated With More Advanced Disease but Better Overall Survival

IntroductionIt is unclear whether nonsmall cell lung cancer (NSCLC) is associated with more aggressive disease and worse overall survival (OS) among younger patients. The aim of this study is to evaluate outcomes in young patients. We hypothesize that young age is associated with more advanced disease upon presentation, but better OS. MethodsWe identified patients with NSCLC from 2004 to 2018 in the National Cancer Database. Patients were categorized in 3 groups: age≤50, 51-84, and ≥85 y. The outcomes were OS, stage IV NSCLC and clinical nodal metastasis. OS was analyzed using multivariate cox and Kaplan–Meier analysis accounting for stage, comorbidities, and other factors. The association of age, presentation with stage IV NSCLC and node positivity was analyzed using multivariate logistic regression. ResultsIn total 1,651,744 patients were identified: 92,506 (5.57%) age ≤50, 1,477,723 (88.90%) age 51-84, and 91,964 (5.53%) age ≥85. Multivariate model showed stage IV NSCLC was associated with age ≤50 (OR 1.17 (1.15-1.20) P < 0.001) and ≥85 (odds ratio (OR) 1.03 (1.02-1.04) P < 0.001). Clinical lymph node positivity was associated with age ≤50 (OR 1.27 (1.23-1.30) P < 0.001). Relative to patients 51-84, the ≤50 group was associated with better survival in Stage I (hazard ratio (HR) 0.61 versus 1.00), stage II (HR 1.12 versus 1.50), stage III (HR 2.12 versus 2.53), and stage IV (HR 6.65 versus 7.53). ConclusionsPatients ≤50-y-old present with more advanced NSCLC, but better OS compared to patients 51-84. These findings suggest the need for increased awareness regarding NSCLC among age groups seen as low risk.

Effects of lobectomy in stage II/IIIA second primary lung cancer patients with prior non-small cell lung cancer: a SEER-based study.

Our study aimed to reveal the prognostic factors of second primary lung cancer and explore the optimal surgical procedure for Stage II/IIIA second primary lung cancerpatients with prior non-small cell lung cancer. Patients with Stage II/IIIA second primary lung cancer were collected from the Surveillance, Epidemiology and End Results database from 2004 to 2016. Lasso regression, along with univariate and multivariate Cox regression, was used to screen prognostic factors. The propensity score matching was used to minimize baseline differences, and restricted mean survival time was used to compare overall survival and cancer-specific survival of different groups. A total of 579 patients were enrolled in the study. After data wasscreened by lasso regression and univariate Cox regression, multivariateCox regression revealed that age, sex, race, tumor size of initial primary lung cancer, tumor size, histological grade, T stage,N stage and surgical procedure of second primary lung cancer were independent prognostic factors. Further analysis showed that surgery, especially lobectomy, provided better survival in Stage II/IIIA second primary lung cancer. Our study identified nine independent prognostic factors of Stage II/IIIA second primary lung cancer. Surgery can provide a better prognosis, and lobectomy might be the optimal surgical procedure for these patients.

Tumor Immune Microenvironment Characteristics and Their Prognostic Value in Non-Small-Cell Lung Cancer.

IntroductionCancer progression is determined not only by the malignant behavior of tumors but also by the immune microenvironment. The tumor immune microenvironment also plays a pivotal role in determining the clinical response of non-small-cell lung cancer (NSCLC) to immunotherapies. To understand the possible mechanisms and explore new targets in lung cancer immunotherapy, we characterized the immune profiles in NSCLC patients.MethodsSeventy-one NSCLC patients who underwent radical resection were selected. The immune cell composition in paired tumor and adjacent normal lung tissues was tested by flow cytometry. The associations of tumor immune microenvironment characteristics with clinicopathological factors and overall survival were analyzed. Kaplan–Meier curves and Cox proportional hazards models were used to determine differences in survival.ResultsCompared with adjacent normal lung tissues, an increased proportion of CD45+ hematopoietic-derived cells, CD4+ T cell subtypes, Tregs and B cells was observed in tumor samples with a reduced frequency of myeloid cell populations. There was no significant increase in total CD8+ T cells, but both PD1+ and CD38+ CD8+ T cells were significantly enriched in tumor samples and statistically significantly associated with tumor size. In addition, positive CD38 expression was highly correlated with PD1 positivity. A high proportion of CD8+ T cells and a low percentage of PD1+ CD8+ T cells were statistically significantly associated with better survival in stage II and III patients, whereas a low frequency of CD38+ CD8+ T cells was statistically significantly associated with better survival in all patients and identified as an independent prognostic factor (p=0.049).ConclusionWe profiled the immune cells in the tumor tissues of NSCLC patients using flow cytometry. The results revealed significant enrichment of infiltrating immune cells. A strong correlation was identified between CD38 and PD-1 expression on CD8+ T cells in tumors. CD8+ T cells and their subtypes play a critical role in the prediction of prognosis.

Survival outcomes of adjuvant chemotherapy in elderly patients with stage III colon cancer.

89 Background: The survival impact of multi-agent (MAC) as compared to single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study is to evaluate the survival outcome comparing MAC to SAC in this population utilizing the National Cancer DataBase (NCDB). Methods: Patients 70 years and older with pathological stage III CC were identified between 2004 and 2015 from the NCDB using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490, and C18.0-18.8 (without C18.1). Univariate and multivariable analyses were conducted and Kaplan-Meier analysis and Cox proportional hazard models were used to identify the association between MAC vs. SAC and overall survival (OS). Results: A total of 41,707 elderly patients (≥70 years old) with stage III CC were identified. Around half of the patients (n = 20,257; 48.5%) received AC; the majority of whom (n = 12,923, 63.8%) received MAC. The median age was 79 (range 70-90). Of the patients who received AC, the majority were female (n = 11,201, 55.3 %), Caucasians (87.4%) and had a moderately differentiated tumor grade (n = 12,619, 62.3%). Tumor size more than 4 cm was identified in 11,785 (58.2%) patients and 18,496 (91.3%) had negative surgical margins. Low-risk stage III CC constituted 50.6% (n = 10,264) of the study population. High-risk stage III CC was associated with worse OS compared to low-risk disease (p &lt; 0.001). MAC was associated with better 5-year OS compared to SAC (p &lt; 0.001). High-risk stage III patients who received MAC had an OS of 4.2 v. 3.4 years in SAC (p &lt; 0.001). In low risk stage III, patients who received MAC had median OS of 8.5 v. 7 years in SAC (p &lt; 0.001). In Univariate, male sex, positive surgical margin, insurance and facility types, age, year of diagnosistumor size, and Charlson-Deyo Score of &gt; 2 were associated with worse OS (p &lt; 0.05). Conclusions: Multi-agent AC is associated with better survival in stage III CC patients 70 years and older compared to SAC. Enhanced benefit of MAC was shown for both low risk and high risk stage III CC.

Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer: Where we Stand; An Italian Single Center Perspective.

Neoadjuvant or perioperative chemotherapy is the standard treatment for locally advanced gastric cancer. However, in Eastern countries this is still debated. The aim of our study was to evaluate the survival impact of neoadjuvant chemotherapy. A total of 60 patients who underwent preoperative chemotherapy were compared to patients with locally advanced gastric cancer that underwent upfront surgery. Median survival of the entire group curatively treated was 41 months with a median progression-free survival of 38 months. By excluding patients with stage IV disease from the neoadjuvant group, a statistically significant difference was reached both in terms of overall survival and disease-free survival. By subdividing patients according to pTNM stages, neoadjuvant patients showed better survival in stage I and II. Neoadjuvant chemotherapy could be an effective treatment for locally advanced disease. However, randomized studies are still needed to fully understand its role and identify patients that will benefit from it.

Impact of time to treatment initiation (TTI) on survival of patients with newly diagnosed non-small cell lung cancer (NSCLC).

9058 Background: Lung Cancer is the leading cause of cancer related deaths in the USA. NSCLC comprises about 85% of lung cancer cases. Although timeliness of care in patients with NSCLC is considered an important aspect of quality care, there are conflicting data about its impact on clinical outcomes. The primary objective of this study is to determine if there is an association between TTI and survival in patients with NSCLC. Methods: In this retrospective study, we reviewed data from our multi-site Mayo Clinic Cancer Center registry and identified patients with newly diagnosed NSCLC from 2000 to 2016. TTI was calculated from time of diagnosis to time of first treatment (surgery, radiation therapy or systemic therapy). Analyses were performed by SAS software 9.4. Log-Rank test was used to compare survival. Cox regression multivariate model was used to evaluate the prognostic value of variables to survival. Results: 10010 patients (53% males and 47%) were reviewed. Median age at diagnosis was 70. Median TTI was 12 days for stage I, and 20 days for stage II, III and IV. We compared outcomes of patients with TTI &gt; 20 days to TTI ≤20 days. Outcomes were stratified based on age, gender, grade, and stage. Median Overall Survival (OS) was significantly better for patients with TTI ≤20 days compared to TTI &gt; 20 days (39.1 vs 28.6 months P-value &lt; 0.0001). Further stratification, based on stage, showed significantly better OS for stage I and II patients with TTI ≤20 days compared to TTI &gt; 20 days (103.4 vs. 63.9 months P-value &lt; 0.0001 and 72.3 vs. 46.8 months P-value 0.0014 respectively). OS for stage III patients with TTI ≤20 days was not significantly different from patients with TTI &gt; 20 days (30.6 vs. 28.5 months P-value 0.118). Interestingly, stage IV patients had worse OS if TTI ≤20 days compared to TTI &gt; 20 days (8.3 vs. 12.8 months P-value &lt; 0.0001). Conclusions: Our study showed an association between TTI and survival of patients with NSCLC. Shorter TTI was associated with better survival in stage I and II patients and worse survival in stage IV patients. Our study further highlights the controversy surrounding the topic of impact of timeliness of care on survival in patients with cancer, specifically NSCLC across different stages.

Prognostic significance of preoperative radiotherapy in stage II and III rectal cancer patients: A Strobe-compliant study of SEER 18 registries database (1988-2011).

Preoperative radiation therapy has been regarded as the optional neoadjuvant treatment to decrease local recurrence of rectal cancer in addition to surgery. However, its benefit in survival remained obscure. This study was aimed to measure the efficacy of preoperative radiation therapy for survival in stage II and III rectal cancer patients. Retrospective cohort study used the database of Surveillance, Epidemiology and End Results program of the National Cancer Institute in the United States from 1988 to 2011. A total of 49439 patients diagnosed with primary rectal cancer who underwent surgery were included. Clinicopathological characteristics and rectal cancer-specific survival between surgery alone group and surgery plus preoperative radiation therapy group were compared. Rectal cancer patients in surgery plus preoperative radiation therapy group had significantly better survival than those in surgery alone group (72.70% vs. 66.61%, P < 0.001), as well as stratified by stages (stage II: 77.4% vs. 74.3%, P < 0.001; stage III: 68.3% vs. 58.6%, P < 0.001). However, this beneficial impact was only observed after 2000s (P < 0.001). Multivariate survival analysis revealed that preoperative radiation therapy was an independent predictor for better survival in stage III (hazard ratio, 0.795; 95% CI, 0.753-0.840; P < 0.001), but not in stage II (P = 0.70). Preoperative radiation therapy might bring a better survival in stage II and III rectal cancer patients, but only as an independent predictor for stage III patients. As time progressed, preoperative radiation therapy might yield more profit for stage II and III rectal cancer patients.

Moderately Hypofractionated Helical IMRT, FDG–PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs

IntroductionThe objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. Methods and MaterialsFrom May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients. ResultsThe median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001). ConclusionsModerately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.

Chemotherapy-induced neutropenia and the prognosis of colorectal cancer: a meta-analysis of cohort studies

ABSTRACTIntroduction: Recently, there has been a controversial discussion about the prognostic value of chemotherapy-induced neutropenia (CIN) in colorectal cancer patients. Thus, a meta-analysis was conducted to determine the relationship between CIN and the prognosis of colorectal cancer patients.Methods: We searched the PubMed, EMBASE, and Cochrane library databases to identify studies evaluating the association between CIN and colorectal cancer prognosis. Pooled random/fixed effect models were used to calculate pooled hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association.Results: Eight studies were selected for the meta-analysis, for a total of 2,745 patients. There was significant improved survival among colorectal cancer patients with CIN (HR = 0.62, 95% CI = 0.47–0.76). However, significant heterogeneity was found (p = 0.000, Ι2 = 75.0%). Through subgroup analysis, we could greatly eliminate the heterogeneity and found that neutropenia was associated with better survival in stage IV colorectal cancer patients, no matter the HR calculated by overall survival (OS) or progression-free survival (PFS). Meanwhile, the prognostic value of neutropenia in stage II/III colorectal cancer can be found when the HR is calculated by disease-free survival (DFS). Additionally, we observed significant differences after stratification according to various tumor stages, endpoints, and the use of G-CSF.Conclusions: Our results which, based on a cohort study, indicate that CIN is associated with improved survival in patients with colorectal cancer. However, further randomized controlled trials are warranted.

Lysosomal acid phosphatase 2 is an unfavorable prognostic factor but is associated with better survival in stage II colorectal cancer patients receiving chemotherapy.

Colorectal cancer (CRC) is one of the leading cancers worldwide. Surgery is the main therapeutic modality for stage II CRC. However, the implementation of adjuvant chemotherapy remains controversial and is not universally applied so far. In this study, we found that the protein expression of lysosomal acid phosphatase 2 (ACP2) was increased in CRC and that stage II CRC patients with high ACP2 expression showed a poorer outcome than those with low ACP2 expression (p = 0.004). To investigate this discrepancy, we analyzed the relation between ACP2 expression and several clinical cofactors.Among patients who received chemotherapy, those with an high expression of ACP2 showed better survival in both stage II and III CRC than those with low ACP2 expression. In stage II CRC patients, univariate analysis showed ACP2 expression and T stage to be cofactors significantly associated with overall survival (ACP2: p = 0.006; T stage: p = 0.034). Multivariate Cox proportion hazard model analysis also revealed ACP2 to be an independent prognostic factor for overall survival (ACP2: p = 0.006; T stage: p = 0.041). Furthermore, ACP2-knockdown CRC cells showed an increase in chemoresistance to 5-FU treatment and increased proliferation marker in the ACP2 knockdown clone.Taken together, our results suggested that ACP2 is an unfavorable prognostic factor for stage II CRC and may serve as a potential chemotherapy-sensitive marker to help identify a subset of stage II and III CRC patients for whom chemotherapy would improve survival.Highlights1. To the best of our knowledge, the study is the first report to show ACP2 overexpression in human colorectal cancer (CRC) and its association with poor outcome in stage II CRC.2. Patients with stage II and III CRCs with high expression of ACP2 were more sensitive to chemotherapy than those with a low expression.3. ACP2 expression may serve as a marker for CRC patients receiving chemotherapy and help identify the subset of CRC patients who would benefit from chemotherapy.

P1.01-035 Trends, Patterns of Treatment and Outcomes in Non-Small Cell Lung Cancer (NSCLC) as a Second Primary: A National Cancer Data Base (NCDB) Analysis

The prevalence of NSCLC as a second primary tumor has been increasing over the past decades, though very little data are available in the literature. We analyzed the NCDB, an oncology outcomes database administered by the American College of Surgeons and the American Cancer Society, to study the outcomes and patterns of treatment of patients (pts) diagnosed with NSCLC as a second or subsequent primary (SP). The NCDB was queried from 2004 to 2012 for NSCLC pts. Pts diagnosed with NSCLC as SP were compared with pts with de novo (DN) NSCLC as defined by sequence number in the database. Univariate (UV) and multivariable analyses (MV) with overall survival (OS) were conducted by Cox proportional hazards model. Kaplan-Meier plots were produced to compare the survival curves by subgroups along with log-rank p-values. A total of 207,518 pts in SP and 697,709 pts in DN groups were included in the analysis, which accounted for 22% and 74% of all NSCLC pts respectively. Pt characteristics (SP/DN %): median age 72/68, male 53/53, white 89/84, stage IV 28/41, treated at academic centers 33/32, government insured 72/57, mean tumor size (cm) 3.5/4.4. An increasing trend in incidence of SP was observed (19.5% in 2004 to 24% in 2012) vs. a decreasing trend in DN (75.6% in 2004 to 73% in 2012). About 12% in SP and 15% in DN received chemotherapy as part of their treatment. Surgery was performed in 39% of SP group vs. 28% in DN. Radiation was given to 43% of the pts in DN vs. 36% in SP. On UV and MV analysis, SP was associated with better survival than DN (HRs 0.84 and 0.93 respectively; p<0.001). The SP group had higher 5-year OS (23% vs. 19.6%, p<0.001) and a higher median survival (17 vs. 11.5 months) compared to DN. On stratifying by stage, DN had inferior survival in stage IV pts (HR 1.12, p<0.001) compared to SP but better survival in stage I and II pts (HRs 0.86 and 0.93, p<0.001). No difference in OS was seen in stage III pts (HR 1.01, p= 0.4). The incidence of second primary has increased over the past decade. Second primary NSCLC is diagnosed at an earlier stage, smaller tumor size, and is associated with a better survival, compared to de novo NSCLC.

Comparable survival for young rectal cancer patients, despite unfavourable morphology and more advanced-stage disease

BackgroundYoung patients with rectal cancer tend to present with more advanced-stage disease and unfavourable tumour morphology. The effects of these tumour characteristics on survival in this particular patient group are unclear. MethodsPopulation-based data from the Netherlands Cancer Registry (NCR) were used. Data from patients diagnosed with rectal cancer between 1989 and 2010 were selected. Younger patients (⩽40years) were compared with middle-aged patients (41–70years) with respect to disease stage, tumour characteristics, treatment and outcomes. Patients aged older than 70years were excluded. Relative excess risk (RER) models were used to perform uni- and multivariate survival analyses. FindingsA total of 37.056 patients were included (⩽40years n=1.102). Compared with middle-aged patients, young patients were more likely to have stage III (33.8% versus 27.8%) and stage IV (24.3% versus 19.6%) disease (p<0.001). Young patients also presented more frequently with mucinous tumours (10.8% versus 9.0%), signet cell carcinomas (2.6% versus 0.6%) and poorly differentiated tumours (16.6% versus 12.3%) (p=0.001). The treatment of stage I–III patients did not differ between the two groups, except regarding adjuvant chemotherapy, which was more often given to young patients (24.3% versus 14.4%, p<0.001). Young age was a prognostic factor for better survival in stage I–III patients (RER 0.82 CI 0.71–0.94). Adjuvant chemotherapy was associated with improved survival in stage I–III patients (RER 0.76, 95%CI 0.70–0.83). In an exploratory analysis, adjuvant chemotherapy in young stage III and pN1 patients was associated with improved survival. Concluding statementYoung patients present with more advanced disease and have more unfavourable tumour characteristics compared with middle-aged patients. Despite these characteristics, survival rates are equal, and young age is a prognostic factor for better survival. Although the use of adjuvant chemotherapy is controversial, a positive correlation with survival was found in this study.

Inhibition of colorectal cancer stem cell survival and invasive potential by hsa-miR-140-5p mediated suppression of Smad2 and autophagy.

Colorectal cancer (CRC) is the third highest mortality cancer in the United States and frequently metastasizes to liver and lung. Smad2 is a key element downstream of the TGF-β signaling pathway to regulate cancer metastasis by promoting epithelial to mesenchymal transition and maintaining the cancer stem cell (CSC) phenotype. In this study, we show that hsa-miR-140-5p directly targets Smad2 and overexpression of hsa-miR-140-5p in CRC cell lines decreases Smad2 expression levels, leading decreased cell invasion and proliferation, and increasing cell cycle arrest. Ectopic expression of hsa-miR-140-5p in colorectal CSCs inhibited CSC growth and sphere formation in vitro by disrupting autophagy. We have systematically identified targets of hsa-miR-140-5p involved in autophagy. Furthermore, overexpression of hsa-miR-140-5p in CSCs abolished tumor formation and metastasis in vivo. In addition, there is a progressive loss of hsa-miR-140-5p expression from normal colorectal mucosa to primary tumor tissues, with further reduction in liver metastatic tissues. Higher hsa-miR-140 expression is significantly correlated with better survival in stage III and IV colorectal cancer patients.The functional and clinical significance of hsa-miR-140-5p suggests that it is a key regulator in CRC progression and metastasis, and may have potential as a novel therapeutic molecule to treat CRC.

Comparison of short and long-term results between sleeve resection and pneumonectomy in lung cancer patients over 70 years old: 10 years experience from a single institution in China.

The aim of this study was to compare the short and long-term results between sleeve resection (SR) and pneumonectomy (PN) in lung cancer patients over 70 years of age. We retrospectively reviewed 105 lung cancer patients over 70 years of age who had undergone SR or PN at Shanghai Chest Hospital from January 2003 to December 2012. The SR group showed a higher frequency of airway clearance via bronchoscopy (48.6% vs. 25.7%, P = 0.04), longer surgical time (162.7 vs. 140.9 minutes, P = 0.01), and shorter postoperative stay (13.7 vs. 18.1 days, P = 0.02) than the PN group. There was no difference in hospital mortality (P = 1.00) or morbidity (P = 0.40) between the two groups. A logistic regression model showed that preoperative predicted forced expiratory volume in 1 second was the only independent risk factor for overall morbidity (P = 0.04). In survival analysis, SR showed better prognosis than PN (median 50.0 vs. 20.0 months, P < 0.01). In subgroup analysis, SR showed better survival in N0 (P = 0.03) and N1 (P < 0.01) cases, but not in N2 cases (P = 0.36). It also showed better survival in stage I + II patients (P = 0.03), but not in stage III patients (P = 0.10). Although PN could be carried out as safely as SR in patients over 70 years of age with a good pulmonary reservoir, SR is still recommended as a less traumatic procedure, sparing lung parenchyma with better long-term results.

Breast cancer survival: Is the Asian population homogenous?

1606 Background: Study of the ER-/PR-/HER2- (TN) subtype has generated interest in race/ethnicity with respect to breast cancer. Poor survival of African-American (AA) women with breast cancer has been reported. Less is known about the Asian population. This study examines survival of four ER/PR/HER2 subtypes among 10 self-reported race/ethnicity categories Methods: Using the California Cancer Registry 2000-2010, we examined 136,175 cases first primary female invasive breast cancer. For stages 1 and 2, Kaplan-Meier survival and the Log-Rank test were computed by stage and race for the ER+/PR+/HER2-, ER-/PR-/HER2+, ER+/PR+/HER2+ (TP) and TN subtypes. Results: When the Asian population is combined into the category Asian/Pacific Islander (API): ER+/PR+/HER2-: AAs had worse 5-year survival than whites in stages 1 and 2 but Hispanics and APIs had better survival in both stages; ER-/PR-/HER2+: AAs and Hispanics were no different from whites in stage 1 but APIs had better 5-year survival (0.96 vs 0.89, p&lt;0.001). For stage 2, there were no differences in survival among the races. ER+/PR+/HER2+: AAs had worse and APIs had better survival in both stages; Hispanics had better survival only in stage 1 (0.93 vs 0.92, p&lt;0.03) and were no different from whites in stage 2. ER-/PR-HER2-: AAs and Hispanics were no different from whites in stage 1 but APIs had better survival (0.93 vs 0.88, p&lt; .003); AAs had worse survival than whites in stage 2 (0.71 vs 0.75, p&lt; 0.04) Hispanics were no different, and APIs had better survival (0.81, p &lt; 0.001). When the Asian population was expanded into 7 categories, Pacific Islanders and Koreans were no different than whites in stages 1 or 2 for all four subtypes examined. For Stage 1, Southeast Asians had better survival for all subtypes except for the TN whereas Filipinos had better survival for all subtypes except for TP. For the ER+/PR+/HER2- subtype, women from the Indian Continent had better survival in stage 1 (0.98 vs 0.92, p&lt;0.003) and in stage 2 (0.94 vs 0.88, p&lt;.001) and better survival for stage 1 of the TN subtype (1.00, vs 0.88, p &lt;0.04). Conclusions: There is heterogeneity among the Asian population, but regardless of how categorized, Asians have either the same or better 5-year survival than whites for all subtypes in stages 1 and 2.

Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) Polymorphism on Outcome of Advanced-Stage Squamous Cell Carcinoma of the Head and Neck Are Treatment Dependent

Germline variation in DNA damage response may explain variable treatment outcomes in squamous cell carcinoma of the head and neck (SCCHN). By grouping patients according to stage and radiation treatment, we compared SCCHN survival with regard to ERCC2 A35931C (Lys751Gln, rs13181) and CCND1 G870A (Pro241Pro, rs9344) genotypes. In a hospital-based SCCHN case series (all white, 24.7% female, mean age 58.4 years), this treatment-outcome cohort study genotyped 275 stage III-IV cases that were initially treated with radiation (with or without chemotherapy) and 80 stage III-IV and 130 stage I-II cases that were initially treated without radiation or chemotherapy and used Kaplan-Meier and Cox regression analyses to compare genotype groups on the basis of overall, disease-specific, progression-free, and recurrence-free survival rates. ERCC2 35931 AA predicted worse survival in stage III-IV cases treated with radiation [multiply-adjusted HR = 1.66, 95% confidence interval (CI), 1.15-2.40; HR over the first 3 follow-up years = 1.92; 95% CI, 1.28-2.88] and better survival in stage III-IV cases not treated with radiation (HR = 0.26; 95% CI, 0.11-0.62). Although not associated with survival in stage III-IV cancers treated with radiation (HR = 1.00; 95% CI, 0.67-1.51), CCND1-870 GG predicted better survival in stage III-IV cancers not treated with radiation (HR = 0.14; 95% CI, 0.04-0.50). Survival in stage I-II did not depend on ERCC2 A35931C or CCND1 G870A genotype. Although promoting tumor progression in untreated patients, germline differences in DNA-repair or cell-cycle control may improve treatment outcome in patients treated with DNA-damaging agents. ERCC2 A35931C may help distinguish advanced stage SCCHN with better outcomes from radiation treatment.

Should Total Number of Lymph Nodes be Used as a Quality of Care Measure for Stage III Colon Cancer?

OBJECTIVE To assess whether TNODS is an independent prognostic factor after adjusting for the lymph node ratio (LNR). SUMMARY BACKGROUND DATA The medical literature has suggested that the TNODS is associated with better survival in stage II and III colon cancer. Thus TNODS was endorsed as a quality measure for patient care by American College of Surgeons, National Quality Forum. There is, however, little biologic rationale to support this linkage. METHODS : A total of 24,477 stage III colon cancer patients were identified from Surveillance, Epidemiology, and End Results cancer registry and categorized into 4 groups, LNR1 to LNR4, according to LNR interval: 0.50. Patients were also stratified according to TNODS into high TNODS (> or = 12) and low TNODS (<12) groups. The method of Kaplan-Meier was used to estimate the 5-year survival and the log-rank test was used to test the survival difference among the different groups. RESULTS Patients with high TNODS have better survival compared with those with low TNODS (5-year survival 51.0% vs. 45.0%, P < 0.0001). However, after stratifying by LNR status, there was no significant survival difference between patients with high TNODS and those with low TNODS within strata LNR2 (5-year survival 56.3% vs. 56.0%, P = 0.26). Ironically, patients with high TNODS had significantly worse survival than those with low TNODS within strata LNR3 (5-year survival 41.2% vs. 47.4%, P = 0.0009) and LNR 4 (5-year survival 22.0% vs. 32.1%, P < 0.0001). CONCLUSIONS The previously reported prognostic effect of TNODS on node-positive colon cancer was confounded by LNR. This observation calls into question the use of TNODS as a quality measure for colon cancer patients' care.

Should Total Number of Lymph Nodes be Used as a Quality of Care Measure for Stage III Colon Cancer?

To assess whether TNODS is an independent prognostic factor after adjusting for the lymph node ratio (LNR). The medical literature has suggested that the TNODS is associated with better survival in stage II and III colon cancer. Thus TNODS was endorsed as a quality measure for patient care by American College of Surgeons, National Quality Forum. There is, however, little biologic rationale to support this linkage. : A total of 24,477 stage III colon cancer patients were identified from Surveillance, Epidemiology, and End Results cancer registry and categorized into 4 groups, LNR1 to LNR4, according to LNR interval: <0.07, 0.07 to 0.25, 0.25 to 0.50, and >0.50. Patients were also stratified according to TNODS into high TNODS (> or = 12) and low TNODS (<12) groups. The method of Kaplan-Meier was used to estimate the 5-year survival and the log-rank test was used to test the survival difference among the different groups. Patients with high TNODS have better survival compared with those with low TNODS (5-year survival 51.0% vs. 45.0%, P < 0.0001). However, after stratifying by LNR status, there was no significant survival difference between patients with high TNODS and those with low TNODS within strata LNR2 (5-year survival 56.3% vs. 56.0%, P = 0.26). Ironically, patients with high TNODS had significantly worse survival than those with low TNODS within strata LNR3 (5-year survival 41.2% vs. 47.4%, P = 0.0009) and LNR 4 (5-year survival 22.0% vs. 32.1%, P < 0.0001). The previously reported prognostic effect of TNODS on node-positive colon cancer was confounded by LNR. This observation calls into question the use of TNODS as a quality measure for colon cancer patients' care.

Early or Up-Front Radiotherapy Improved Survival of Localized Extranodal NK/T-Cell Lymphoma, Nasal-Type in the Upper Aerodigestive Tract

To investigate the role of early or up-front radiotherapy (RT), the optimal RT dose required to achieve appropriate treatment outcome and prognostic factors for patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. Eighty-two patients were reviewed. Eight patients were treated with chemotherapy (CT) alone, 9 patients received RT alone, and 65 patients were given combined modality treatment of CT and RT (CMT). Of those 74 patients receiving RT, 31 patients were given up-front RT, whereas CT was the initial therapy for 43 patients and 41 of those 43 patients received early RT. Five-year overall survival (OS) and disease-free survival (DFS) were 52.3% and 39.2%, respectively. RT was the only independent prognostic factor for both OS and DFS at both the univariate and multivariate level. The 5-year OS and DFS were better in patients receiving >or=54 Gy of RT as compared with that of <54 Gy (5-year OS 75.5% vs. 46.1%, p = 0.019; 5-year DFS 60.3% vs. 33.4%, p = 0.004). Up-front RT presented better survival in Stage I patients when compared with that of initial CT followed by early RT (5-year OS 90.0% vs. 48.9%, p = 0.012; 5-year DFS 78.7% vs. 39.9%, p = 0.021). Early or up-front RT had an essential role in improved OS and DFS in patients with localized extranodal NK/T-cell lymphoma, nasal-type, in the upper aerodigestive tract. The recommended tumor dose was at least 54 Gy. Up-front RT may yield more benefits on survival in patients with Stage I disease.

Proliferation kinetics and prognosis in gastric cancer after resection

The influence of proliferation and proliferation kinetics on prognosis in gastric cancer after complete resection are controversial. In a prospective study we investigated the tumour specimens of 111 patients after resection of gastric cancer, who received 200 mg intravenous (i.v.) bromodeoxyuridine (BrdU) pre-operatively. The following biological parameters were analysed in the tumour tissue using flow-cytometry: DNA ploidy, proportion of S-phase cells, BrdU labelling index (LI), DNA synthesis time (Ts), potential tumour doubling time (Tpot), proliferating cell nuclear antigen (PCNA) and Ki-67 LI. The median follow-up time was 40 months (range 19–62 months). Besides the established pathohistological prognostic factors, univariate analysis revealed a prognostic influence on survival for BrdU LI, Tpot and the proportion of S-phase cells. By multivariate Cox analysis of the completely resected cases, only tumour stage and Tpot had a significant, independent influence on survival. By classification and regression trees (CART) analysis, resection status, tumour stage and Tpot defined risk groups with significantly different outcomes. A short Tpot was a predictor of better survival in stage I, II and IIIA tumours. Ploidy and the other investigated proliferation-related parameters failed to demonstrate any influence on prognosis after resection of gastric cancer.