Additional Prognostic Factors Research Articles

Asses microvascular densities in breast ductal cell carcinoma (using CD 31 & VWF immunostain), in correlation to ER status

For three years duration( Jan 2009 – Des 2011) , 50 cases of ER positive cases and 50 cases of ER negative cases were collected among mastectomy samples from patients with invasive ductal carcinoma of the breast which were received by the department of histopathology in AL -Hilla teaching hospital. microvessel density (MVD) estimation for all cases using CD – 31 & VWF immunostain, and the quantitative analyses of the microvessels in the 10 high power fields revealed the median for vessels count identified by anti-CD31 in ER-positive & ER- negative groups were( 18, 30) respectively, while median MVD as it expressed by anti-VWF in ER-positive & ER-negative groups were (19, 33) respectively. There were greater concentrations of microvessels stained brown by both antibodies (CD31 & VWF) in estrogen receptors- negative group compared to the estrogen receptors – positive group. This difference was statistically significant (p< 0.001) .The highest values of MVD were obtained using anti-VWF other than anti-CD31 & the median MVD was significantly different between those two antibodies (p <0.005). So the
 conclusion is that, high vessels count represent increased tumor angiogenesis and correlated with estrogen status, and tumor grade. Microvessels quantitation may be an additional prognostic factor especially when it combined with more established parameters like estrogen receptor status.

Meta-analysis of determinants of survival following treatment of recurrent hepatocellular carcinoma.

Intrahepatic recurrence of hepatocellular carcinoma (HCC) following resection is common. However, no current consensus guidelines exist to inform management decisions in these patients. Systematic review and meta-analysis of survival following different treatment modalities may allow improved treatment selection. This review aimed to identify the optimum treatment strategies for HCC recurrence. A systematic review, up to September 2016, was conducted in accordance with MOOSE guidelines. The primary outcome was the hazard ratio for overall survival of different treatment modalities. Meta-analysis of different treatment modalities was carried out using a random-effects model, with further assessment of additional prognostic factors for survival. Nineteen cohort studies (2764 patients) were included in final data analysis. The median 5-year survival rates after repeat hepatectomy (525 patients), ablation (658) and transarterial chemoembolization (TACE) (855) were 35·2, 48·3 and 15·5 per cent respectively. Pooled analysis of ten studies demonstrated no significant difference between overall survival after ablation versus repeat hepatectomy (hazard ratio 1·03, 95 per cent c.i. 0·68 to 1·55; P = 0·897). Pooled analysis of seven studies comparing TACE with repeat hepatectomy showed no statistically significant difference in survival (hazard ratio 1·61, 0·99 to 2·63; P = 0·056). Based on these limited data, there does not appear to be a significant difference in survival between patients undergoing repeat hepatectomy or ablation for recurrent HCC. The results also identify important negative prognostic factors (short disease-free interval, multiple hepatic metastases and large hepatic metastases), which may influence choice of treatment.

Low-grade and high-grade endometrial stromal sarcoma: A National Cancer Database study

ObjectiveTo provide refined prognostic information from large cohorts of women with low-grade or high-grade endometrial stromal sarcoma (ESS). MethodsWe performed an observational retrospective cohort analysis of women diagnosed with low-grade or high-grade ESS from the 1998–2013 National Cancer Database. Kaplan-Meier and multivariable accelerated failure time survival analyses were performed to identify prognostic factors after multiple imputation of missing data. Recursive partitioning methods were used to rank prognostic factors in high-grade ESS. Matched cohort analyses were performed to hypothesis-test effects of adjuvant treatments. ResultsWe identified 2414 and 1383 women with low-grade or high-grade ESS, respectively. Women with high-grade ESS had markedly decreased survival compared to women with low-grade ESS (five-year survival (95% CI): 32.6 (30.1–35.3%) versus 90.5% (89.3–91.8%), P<0.001). Among women with high-grade ESS, median survival (95% CI) was only 19.9 (17.1–22.1) months. Increased age and tumor size were associated with decreased survival in low-grade ESS. In high-grade ESS, additional negative prognostic factors were distant or nodal metastasis, omission of lymphadenectomy, and pathologically-positive surgical margins (all P<0.001). Use of adjuvant chemotherapy (time ratio (TR) (95% CI): 1.36 (1.17–1.58), P<0.001) and radiotherapy (TR (95% CI): 1.57 (1.32–1.87), P<0.001) were associated with increased survival for high-grade ESS. ConclusionThe contrasting excellent versus poor prognosis of low-grade versus high-grade ESS, respectively, was confirmed. The best treatment of high-grade ESS is early and complete surgical resection including lymphadenectomy. Adjuvant chemotherapy and radiotherapy may increase survival of women with high-grade ESS.

38 - Utilization of a SNP Microarray for the Study of Multiple Myeloma Patients: Novel Findings and Better Stratification of Patients

Multiple myeloma (MM) is a plasma cell malignancy and serious disorder of the elderly accounting for ~10% of hematologic disorders. It has a variable clinical course and genetic anomalies have been demonstrated as important prognostic factors. However, only around 30% of MM patients have an abnormal karyotype and only 80% of MM patients have genetic alterations that are detected by FISH. In this study, a total of 413 samples from patients confirmed to have MM were studied after plasma cell enrichment using a whole genome SNP microarray analysis along with FISH for the three major translocations. The array detected abnormalities in 99.9% of the samples, and when FISH analysis was abnormal, detected additional findings in 99.8% of those samples. It also showed additional poor prognostic factors, not detectable by standard FISH, such as 12p deletions, a gain of MYC, chromothripsis, and hypodiploidy. Additionally, copy-neutral loss of heterozygosity was detected in a much greater frequency than expected (28.7%). Furthermore, the array revealed changes suggesting a poorer prognosis within patients that had factors thought to be associated with a better prognosis, such as hyperdiploidy or an 11;14 translocation. Additional disorders, such as myelodysplasia or CLL, were detected by the array that would have otherwise not been detected by myeloma FISH. This was particularly evident when the negative fraction of the enrichment analysis was also studied. Overall, these findings indicate that the array is clearly more effective in detecting abnormalities than FISH alone and has added information in providing better prognostic information.

P-240 - suPAR as an additional prognostic factor in colorectal cancer

P-240 - suPAR as an additional prognostic factor in colorectal cancer

Surgery of the primary tumor improves survival in women with stage IV breast cancer in Southwest China: A retrospective analysis.

The International Consensus Guidelines for advanced breast cancer (ABC) considers that the surgery of the primary tumor for stage IV breast cancer patients does not usually improve the survival. However, studies have showed that resection of the primary tumor may benefit these patients. The correlation between surgery and survival remains unclear.The impact of surgery and other clinical factors on overall survival (OS) of stage IV patients is investigated in West China Hospital. Female patients diagnosed with stage IV breast cancer between 1999 and 2014 were included (N = 223). Univariate and multivariate analysis assessed the association between surgery and OS.One hundred seventy-seven (79.4%) underwent surgery for the primary tumor, and 46 (20.6%) had no surgery. No significant differences were observed in age at diagnosis, T-stage, N-stage, histological grade, molecular subtype, hormone receptor (HR), and number of metastatic sites between 2 groups. Patients in the surgery group had dramatically longer OS (45.6 vs 21.3 months, log-rank P < .001). In univariate analysis, survival was associated with surgical treatment, residence, tumor size, lymph node, HR status, hormonal therapy, and radiotherapy. In multivariate analysis, surgery was an independent prognostic factor for OS [hazard ratio (HR), 0.569; 95% confidence interval (CI) 0.329-0.984, P = .044]. Additional independent prognostic factors were hormonal therapy (HR, 0.490; 95% CI 0.300-0.800) and radiotherapy (HR, 0.490; 95% CI 0.293-0.819). In addition, a favorable impact of surgery was observed by subgroup analysis.Our study showed that surgery of the primary breast tumor has a positive impact on OS in with stage IV breast cancer patients.

Effects of Adjuvant Radiotherapy in Patients With Synovial Sarcoma.

To analyze the treatment outcomes and the effects of adjuvant radiotherapy (RT) in patients with synovial sarcoma (SS). The medical records of 103 patients treated with definitive surgery for SS, with/without RT, from August 1982 to July 2013 were reviewed retrospectively. The median age of the patients was 33 years (range, 5 to 72 y). The most frequent tumor location was the extremities (79 patients, 77%). Seventy-five patients (73%) received adjuvant RT and 26 (25%) did not. The median dose of adjuvant RT was 61.2 Gy (range, 45 to 66.6 Gy). The median follow-up period was 5.4 years (range, 0.2 to 31.0 y). The 5- and 10-year overall survival rates were 77 % and 65%, respectively. The progression-free survival (PFS) rates at 5 and 10 years were 52% and 43%, respectively. The most common site of initial failure was the lung (24 patients), followed by local recurrence (14 patients). The 5-year local-recurrence-free survival (LRFS) and distant-metastasis-free survival (DMFS) rates were 80% and 63%, respectively. On multivariate analysis, a mitosis count of <10 per 10 high-power fields (HPF) was a significant predictor of better overall survival, PFS, LRFS, and DMFS (P=0.004, <0.001, 0.025, and <0.001, respectively). Adjuvant RT was an additional prognostic factor for better PFS and LRFS (P=0.006 and 0.028, respectively). A positive/uncheckable resection margin was associated with poor prognosis for DMFS (P=0.011). There was no significant difference in LRFS between the higher and lower RT dose groups (<63 Gy group, 89%; ≥63 Gy group, 88%; P=0.772). The lung and primary site were frequent sites of failure in patients treated with definitive surgery for SS. Adjuvant RT improved LRFS and PFS. Frequent mitotic figures (≥10 mitoses per 10 HPF) were the worst prognostic factor for these patients.

Overview of the 8th Edition TNM Classification for Head and Neck Cancer.

The main purpose of the TNM system is to provide an anatomic-based classification to adequately depict cancer prognosis. Accurate cancer staging is important for treatment selection and outcome prediction, research design, and cancer control activities. To maintain clinical relevance, periodical updates to TNM are necessary. The recently published 8th edition TNM classification institutes the following changes to the staging of head and neck (excluding thyroid cancer): new stage classifications [HPV-related oropharyngeal cancer (HPV+ OPC) and soft tissue sarcoma of the head and neck (HN-STS)] and modification of T and N categories [T and N categories for nasopharyngeal cancer (NPC), T categories for oral cavity squamous cell carcinomas (OSCC), N categories for non-viral related head and neck cancer and unknown primary (CUP), and T categories for head and neck cutaneous carcinoma]. These changes reflect better understanding tumor biology and clinical behavior (e.g., HPV+ OPC and HN-STS), improved outcomes associated with technical advances in diagnosis and treatment (e.g., NPC), evolving knowledge about additional prognostic factors and risk stratification from research and observation (e.g., inclusion of depth of invasion variable for OSCC, inclusion of extranodal extension variable for all non-viral head and neck cancer, and reintroduction of size criteria for non-Merkel cell cutaneous carcinoma of the head and neck). This review summarizes the changes and potential advantages and limitations/caveats associated with them. Further evidence is needed to evaluate whether these changes would result in improvement in TNM stage performance to better serve the needs for clinical care, research, and cancer control.

The maximum standardized uptake value increment calculated by dual-time-point 18F-fluorodeoxyglucose positron emission tomography predicts survival in patients with oral tongue squamous cell carcinoma.

ABSTRACTThe aim of this study was to investigate the prognostic value of dual-time-point (DTP) 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) imaging in primary oral tongue squamous cell carcinoma (OTSCC). The study included 52 patients who underwent preoperative 18F-FDG PET scans at two time points, namely 1 h and 2 h after injection. The following PET parameters were calculated: maximum standardized uptake value (SUVmax) for both time points (SUV early, SUV delayed); retention index (RI); and SUVmax increment (ΔSUVmax). Receiver operating characteristic (ROC) curve analysis was performed to define the optimal cutoff point for these parameters. Overall survival was calculated using the Kaplan–Meier method. Prognostic factors for patients with OTSCC were evaluated using the univariate log-rank test and a multivariate Cox proportional hazards model. ROC analysis revealed that the area under the curve was higher and more accurate for ΔSUVmax than for the other parameters. Additionally, patients with a ΔSUVmax ≥0.9 had significantly worse survival outcomes (28.9% vs 92.6%; p < 0.01). Univariate analysis showed that prognosis was significantly correlated with clinical T stage, local recurrence, perineural invasion, vascular invasion, and PET parameters (p < 0.05 for all). Multivariate analysis showed that local recurrence (hazard ratio = 3.60; p = 0.02) and ΔSUVmax (hazard ratio = 8.43; p < 0.01) were independent prognostic factors. ΔSUVmax determined using DTP 18F-FDG PET may be an additional prognostic factor in OTSCC patients.

The lymph node ratio as an independent prognostic factor for node-positive triple-negative breast cancer.

BackgroundWe aimed to evaluate the prognostic value of the lymph node ratio (LNR) in patients with axillary lymph node-positive triple-negative breast cancer (TNBC).MethodsThe prognostic efficacy was investigated in the first cohort from the Surveillance, Epidemiology, and End Results (SEER) dataset (n=4114) and was further validated in an independent cohort from Fudan University Shanghai Cancer Center (n=417). Patients were classified into low-, medium- and high-risk LNR groups.ResultsMultivariate analysis revealed that the LNR was an independent predictor of overall survival (hazard ratio (HR) for high-risk LNR: 3.24; 95% confidence interval (CI): 2.56 to 4.09) and breast cancer-specific survival (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER population and also for disease-free survival (HR for high-risk LNR: 4.29; 95% CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that patient classification according to the LNR could discriminate among groups of patients with different survival rates based on pathological nodal (pN) staging.ConclusionThe LNR shows potential for use as an additional prognostic factor for TNBC patients with positive lymph node involvement. Considering the heterogeneity of TNBC, use of the LNR might allow for optimization of the pN staging system and should be considered when making treatment decisions.

The Pretreatment Neutrophil-to-Lymphocyte Ratio is a Prognostic Determinant of T3-4 Hypopharyngeal Squamous Cell Carcinoma.

This study aimed to investigate the clinicopathological factors that influence recurrence and survival in patients who undergo operations for T3-4 hypopharyngeal squamous cell carcinomas (SCCs). One hundred and five patients who underwent surgery between 2001 and 2008 for advanced hypopharyngeal SCCs were consecutively enrolled and reviewed. The pretreatment neutrophil-to-lymphocyte ratio (NLR; median 3.22, range 0.62-46.50) was associated with disease recurrence and patient survival. A difference in the 5-year cumulative disease recurrence rate between patients with high (≥3.22) and low (<3.22) NLRs was significant (60.4 and 36.5%, respectively; p=0.004). A multivariate analysis confirmed that an NLR≥3.22 was an independent indicator of a poor prognosis for advanced hypopharyngeal SCC, as per the following parameters: overall survival (hazard ratio [HR] 2.53, 95% confidence interval [CI] 1.48-4.30, p=0.001), disease-specific survival (HR 2.45, 95% CI 1.38-4.34, p=0.002), and disease-free survival (HR 2.18, 95% CI 1.24-3.83, p=0.007). Additional prognostic factors per the survival analyses included lymph node density, surgical margin, lymphovascular invasion, and perineural invasion. An NLR≥3.22 is associated with a higher risk of disease recurrence and poor survival in patients with T3-4 hypopharyngeal SCCs. We propose the use of the NLR to broaden the current TNM staging system; the development of a more effective treatment protocol for patients with high NLRs will be essential.

Stress Perfusion CMR in Patients With Known and Suspected CAD: Prognostic Value and Optimal Ischemic Threshold for Revascularization

ObjectivesThis study sought to determine the ischemia threshold and additional prognostic factors that identify patients for safe deferral from revascularizations in a large cohort of all-comer patients with known or suspected coronary artery disease (CAD). BackgroundStress-perfusion cardiac magnetic resonance (CMR) is increasingly used in daily practice for ischemia detection. However, there is insufficient evidence about the ischemia burden that identifies patients who benefit from revascularization versus those with a good prognosis who receive drugs only. MethodsAll patients with known or suspected CAD referred to stress-perfusion CMR for myocardial ischemia assessment were prospectively enrolled. The CMR examination included standard functional adenosine stress first-pass perfusion (gadobutrol 0.1 mmol/kg Gadovist, Bayer AG, Zurich, Switzerland) and late gadolinium enhancement (LGE) acquisitions. Presence of ischemia and ischemia burden (number of ischemic segments on a 16-segment model), and of scar and scar burden (number and transmurality of scar segments in a 17-segment model) were assessed. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction (MI), and late coronary revascularization (>90 days post-CMR); the secondary endpoint was a composite of cardiac death and nonfatal MI. ResultsDuring a follow-up of 2.5 ± 1.0 years, 86 and 32 of 1,024 patients (1,103 screened patients) experienced the primary and secondary endpoints, respectively. On Kaplan-Meier curves for the primary and secondary endpoints, patients without ischemia had excellent outcomes that did not differ from patients with <1.5 ischemic segments. In multivariate Cox regression analyses of the entire population and of the subgroups, ischemia burden (threshold: ≥1.5 ischemic segments) was consistently the strongest predictor of the primary and secondary endpoints with hazard ratios (HRs) of 7.42 to 8.72 (p < 0.001), whereas age (≥67 years), left ventricular ejection fraction (≤40%), and scar burden (LGE score ≥0.03) contributed significantly, but to a lesser extent, in all models with HRs of 2.01 to 3.48, 1.75 to 1.96, and 1.66 to 1.76, respectively. ConclusionsIn a large all-comer patient cohort with known and suspected CAD, an ischemia burden of ≥1.5 ischemic segments on stress-perfusion CMR was the strongest predictor of the primary and secondary endpoints. Patients with zero or 1 ischemic segment can be safely deferred from revascularizations.

Determinants of outcome and survival following treatment of recurrent hepatocellular carcinoma: a systematic review & meta-analysis

Objective: This review aimed to identify the optimum treatment strategies for hepatocellular carcinoma (HCC) recurrence. Methods: A systematic review, up to July 2015, was conducted in accordance with MOOSE guidelines. The primary outcome was the hazard ratio for overall survival of different treatment modalities. Meta-analysis of differing treatment modalities was carried out using a random effects model with further assessment of additional prognostic factors for survival. Results: 18 cohort studies (2662 patients) were included in final data analysis. The median 5-year survival of repeat hepatectomy (RH; n = 481 pts), ablation (n = 389) and transarterial chemoembolization (TACE; n = 878) were 43.0%, 52.7% and 9.0% respectively. Pooled analysis of 10 studies demonstrated no significant difference between overall survival after RH or ablation (HR = 1.03; p = 0.897). Median tumor size across these studies was 23.0 mm (RH) and 20.5 mm (ablation). Pooled analysis of 7 studies comparing TACE with RH showed a non-significant trend to improved survival from RH (HR = 1.61; p = 0.056). Review of prognostic factors identified those negatively associated with overall survival includes: recurrence of HCC within one year (HR 6.8; p < 0.05), presence of more than 3 recurrent tumors (HR 3.78; p < 0.05) and tumors greater than 3 cm in size (HR 4.01; p < 0.05). Conclusion: There was significant heterogeneity in the reporting of these studies preventing the implementation of formal meta-regression. Despite a paucity of available data, these results suggest a non-significant trend to improved survival following RH compared with TACE and identification of important negative prognostic factors, which may influence choice of treatment modality.

Abstract P6-09-43: Bcl2 as a long-term prognostic factor in invasive lobular carcinoma of the breast

Abstract Background: B-cell lymphoma 2 (Bcl2) is an anti-apoptotic protein with known tumor suppressor effect in breast cancer. Multiple studies have shown that high Bcl2-expression is associated with a better prognosis in breast cancer, but its clinical usefulness as a prognostic factor is still not fully elucidated. Invasive lobular carcinoma (ILC) of the breast is the second most common histologic subtype and comprises 5 to 15 % of all breast cancers. ILC has distinct clinico-pathological features and a specific pattern of recurrence, but treatment strategies are often similar as for the whole group of breast cancers. ILC´s are typically estrogen receptor positive (ER+), progesterone receptor positive (PgR+), HER2 negative, low proliferative and histological grade 2. According to the St Gallen surrogate definitions of the intrinsic subtypes of breast cancer most ILC´s are classified as 'luminal disease' and predominantly as low-risk 'luminal A-like'. Patients with 'luminal disease' in general and 'luminal A-like' in particular falls into prognostic categories where uncertainty about optimal treatment strategy often arises, as clinicians seek to avoid both over- and under-treatment. Additional prognostic factors are needed in order to further improve risk stratification. The use of multigene assays to better predict recurrence is increasing, but the availability is still limited and the cost is high. Measurement of apoptosis-related factors, such as Bcl2 gene expression is included as a prognosticator in a majority of these tests. The aim of this retrospective study was to evaluate the long-term prognostic effect of Bcl2 in a subset of patients with ILC. Patients and methods: One hundred and ninety-two well-characterized patients with primary ILC were included in the present study. Bcl2 was evaluated together with ER, PgR, HER2, Ki67, histological grade, tumor size, nodal status and age at diagnosis. Ninety-two percent of the patients were ER and/or PgR positive and 41% were node positive. Forty-one percent of the patients received adjuvant endocrine treatment and 3% received adjuvant chemotherapy. The median follow-up of the 52 patients still alive was 26 years. Bcl2 was analyzed immunohistochemically on whole sections of tumor tissue and Bcl2-positivity (Bcl2+) was defined as more than 10% cells with stained cytoplasma. Eighty-six percent of the patients (165/192) were Bcl2+. The primary endpoint was breast cancer mortality (BCM). Results: Overall, 32% (61/192) of the patients have died from breast cancer. Bcl2 (positive vs negative) was a significant prognostic factor for BCM in univariable Cox regression analysis (HR 0.44, 95% CI: 0.23-0.85). Essentially the same Bcl2 effect was seen after multivariable adjustment for ER, Ki67, histological grade, tumor size, nodal status, age at diagnosis and adjuvant therapy (HR 0.33, 95% CI: 0.15-0.74). Conclusions: Bcl2 is an independent long-term prognostic factor in this subset of patients with ILC. Bcl2 might add new prognostic information based on apoptotic tumor features that could be useful in the clinical treatment decision-making. Citation Format: Narbe U, Forsare C, Bendahl P-O, Rydén L, Ingvar C, Fernö M. Bcl2 as a long-term prognostic factor in invasive lobular carcinoma of the breast [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P6-09-43.

Abstract P2-05-15: The lymph node ratio as an independent prognostic factor for node-positive triple-negative breast cancer

Abstract Purpose: To evaluate the prognostic value of the lymph node ratio (LNR) in patients with axillary lymph node-positive triple-negative breast cancer (TNBC). Patients and methods: Based on X-tile plots, we classified women into low-, medium-, and high-risk LNR groups. Univariate and multivariate Cox proportional hazards regression analyses for overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were performed. The prognostic efficacy of the LNR was investigated in the first cohort from the Surveillance, Epidemiology, and End Results (SEER) database (n=4114) and was further validated in an independent cohort from Fudan University Shanghai Cancer Center (n=417). Results: The patients were classified into low- (≤0.30), medium- (0.30 to 0.70) and high-risk (&amp;gt;0.70) LNR groups. Multivariate analysis revealed that the LNR was an independent predictor of OS (hazard ratio (HR) for high-risk LNR: 3.24; 95% confidence interval (CI): 2.56 to 4.09) and BCSS (HR for high-risk LNR: 3.57; 95% CI: 2.76 to 4.62) in the SEER population and also for DFS (HR for high-risk LNR: 4.29; 95% CI: 2.24-8.21) in the validation population. Subgroup analysis revealed that patient classification according to the LNR could discriminate among groups of patients with different survival rates based on pN staging. Effect of Lymph Node Ratio and pN Classification on Survival Among Patients from SEERVariableOSBCSS HR a(95% CI)PHR a(95% CI)PLymph node ratio Low,≤0.301-1-Medium, &amp;gt;0.30 and ≤0.702.05(1.63-2.59)&amp;lt;0.0012.26(1.75-2.92)&amp;lt;0.001High,&amp;gt;0.703.24(2.56-4.09)&amp;lt;0.0013.57(2.76-4.62)&amp;lt;0.001pN N11-1-N21.53(1.21-1.93)&amp;lt;0.0011.63(1.27-2.10)0.001N32.72(2.14-3.46)&amp;lt;0.0012.97(2.29-3.85)&amp;lt;0.001a Cox proportional hazards model. Hazard ratios are adjusted for age, race, histologic grade, tumor size, surgery type and radiotherapy. Conclusion: The LNR shows potential for use as an additional prognostic factor for TNBC patients with positive lymph node involvement. Considering the heterogeneity of TNBC, use of the LNR might allow for optimization of the pN staging system, and this ratio should be considered when making treatment decisions. Citation Format: He M, Jiang Y-Z, Tang L-C, Chen Y-L, Shao Z-M, Di G-H. The lymph node ratio as an independent prognostic factor for node-positive triple-negative breast cancer [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-05-15.

Transition from LDR to HDR brachytherapy for cervical cancer: Evaluation of tumor control, survival, and toxicity

PurposeIn 2012, our institution transitioned from low-dose-rate (LDR) brachytherapy to high dose-rate (HDR) brachytherapy. We report clinical outcomes after brachytherapy for cervical cancer at our institution over a continuous 10-year period. Methods and MaterialsFrom 2004 to 2014, 258 women (184 LDR and 74 HDR) were treated with tandem and ovoid brachytherapy in the multidisciplinary management of International Federation of Gynecology and Obstetrics Stages IA–IVB cervical cancer. Clinical and treatment-related prognostic factors including age, stage, smoking status, relevant doses, and toxicity data were recorded. ResultsMedian followup for the LDR and HDR groups was 46 months and 12 months, respectively. The majority of patients (92%) received external beam radiotherapy as well as concurrent chemotherapy (83%) before the start of brachytherapy. For all stages, the 1-year local control and overall survival (OS) rates were comparable between the LDR and HDR groups (87% vs. 81%, p = 0.12; and 75% vs. 85%, p = 0.16), respectively. Factors associated with OS on multivariate analysis include age, stage, and nodal involvement. On multivariate analysis, severe toxicity (acute or chronic) was higher with HDR than LDR (24% vs. 10%, p = 0.04). Additional prognostic factors associated with increased severe toxicity include former/current smokers and total dose to lymph nodes. ConclusionsThis comparative retrospective analysis of a large cohort of women treated with brachytherapy demonstrates no significant difference in OS or local control between the LDR and HDR. Acute and chronic toxicity increased shortly after the implementation of HDR, highlighting the importance of continued refinement of HDR methods, including integrating advanced imaging.

Transarterial chemo-embolisation of hepatocellular carcinoma: impact of liver function and vascular invasion

Background:Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI).Methods:In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival.Results:Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI.Conclusions:The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown.

Glasgow prognostic score after concurrent chemoradiotherapy is a prognostic factor in advanced head and neck cancer.

Objective This study aims to evaluate the impact and potential prognostic roles of the pre- and post-treatment Glasgow prognostic score (GPS) and the change thereof in patients with advanced head and neck cancer undergoing concurrent chemoradiotherapy (CCRT).Methods We collected GPS and clinicopathological data of 139 stage III, IVA, and IVB head and neck cancer patients who underwent CCRT between 2008 and 2011. Their GPSs pre- and post-CCRT and the change thereof were analyzed for correlations with recurrence and survival. Results The GPS changed in 72 (51.8%) patients, with worse scores observed post-CCRT in 65 (90.3%) of the GPS changed patients. Patients in the improved GPS group showed a tendency toward better survival. From the multivariate analysis, the post-CCRT GPS level was an independent prognostic factor in addition to tumor stage. Conclusions After CCRT, a high GPS was revealed to be an important predictor of survival for advanced head and neck cancer.

Preconditioning Neutropenia Is a Key Prognostic Factor in Allogeneic Hematopoietic Cell Transplantation for High Risk Acute Myeloid Leukemia

Identification of prognostic indicators to predict outcomes of hematopoietic cell transplantation (HCT) is important for selection of patients most likely to benefit from the procedure. Widely validated systems such as the HCT-Comorbidity Index (HCT-CI) and the modified EBMT risk score provide consistent prediction of outcomes, in particular non-relapse mortality (NRM) and survival. In this retrospective study we identified neutropenia prior to initiation of conditioning regimen as an additional prognostic factor in 117 adults with high risk acute myeloid leukemia (AML) who received HCT at a single institution from January 2005 to December 2015. The main endpoints of the study were day 100 non-relapse mortality and survival at 5 years.The median age at HCT was 50 years (range 21-68); 65% had an EBMT score of ≥4. In total 107 (91%) patients had poor risk disease, with classification for poor risk including; patients undergoing HCT due to failure to achieve complete remission (CR) after induction chemotherapy, patients in 2nd CR, patients in 1st CR with adverse karyotype, patients with standard karyotype but with a FLT-3 mutation, patients with measurable residual disease (MRD) by immunophenotyping or molecular monitoring and patients with secondary AML. Conditioning was myeloablative (Cy-TBI: N=41, Bu-Cy: N=3) for patents younger than 51 years with good performance status; the intensity of conditioning was reduced for the others (N=73). Standard methotrexate and cyclosporine was used as graft versus host disease prophylaxis in recipients of sibling cells, and unrelated graft recipients also received alemtuzumab.With a median follow-up of 3.1 years (range 0.3 - 10.0), day 100 NRM for the whole group was 17.3% (95% confidence interval (CI) 11 - 25) and the probability of survival at 5 years was 40.3% (95% CI 31 - 50). The effects of patient, disease and transplant factors were analysed in univariate analyses on both NRM and survival. Significant factors were then entered into multivariate analyses which yielded significant associations with improved NRM for preconditioning absolute neutrophil count (ANC) >= 1000/microL and HCT-CI < 3 (Figure) (hazard ratio (HR) 0.36; 95% CI 0.1 - 0.9 and HR 0.39; 95% CI 0.2 - 0.9 respectively). The factors associated with improved survival in multivariate analysis included preconditioning neutrophil count >= 1000/microL (HR 2.9; 95% CI 1.6 -5.4, P= 0.01), absence of any measurable disease prior to conditioning (HR 2.1; 95% CI 1.1 -4.2, P= 0.03), and less than 2 disease risk defining criteria (HR 15.8; 95% CI 2.0 -124.4, P= 0.01).In conclusion, patients with ANC of 1000/microL and above prior to initiation of conditioning and those with HCT-CI below 3 had significantly better day 100 NRM. ANC of 1000/microL or above was also associated with better survival at 5 years together with disease specific factors, absence of measurable residual disease prior to initiation of condition and less than two adverse prognostic factors. A simple measurement such as the neutrophil count helps to predict outcome: this might reflect the presence of on-going disease but it is also possible that delaying transplant until neutrophil count recovery might impact favourably on the results. Our findings therefore advocate integration of preconditioning neutrophil count into existing risk assessment tools when considering HCT. [Display omitted] DisclosuresMilojkovic:Bristol Myers Squibb: Honoraria; Pfizer: Honoraria; Ariad: Honoraria; Novartis: Honoraria.

Prognostic Significance of 11q23/MLL Fusion Partners in Children with Acute Myeloid Leukemia (AML) - Results from the Children's Oncology Group (COG) Trial AAML0531

Background: Rearrangement of chromosome 11q23 at KMT2A (MLL+) occurs in ~20% of childhood acute myeloid leukemia (AML) cases and is the most common recurrent cytogenetic abnormality in childhood AML. More than 80 fusion partners of MLL have been characterized and the prognostic impact varies by partner and additional cytogenetic aberrations (ACAs). We previously reported superior event-free-survival (EFS), overall survival (OS), relapse risk (RR) and disease free survival (DFS) for patients with MLL+ on AAML0531 treated with gemtuzumab ozogamicin (GO). The impact of fusion partners has not been described for this trial cohort.Objective: To determine the impact of 11q23/MLL+ fusion partners on outcomes for children with AML who were treated uniformly on AAML0531.Methods: AAML0531 (2006 - 2010) was a randomized phase 3 trial of GO with conventional chemotherapy for children, adolescents, and young adults, ages 0 to 29 years, with de novo AML. The trial enrolled 1022 eligible patients without Down syndrome, and cytogenetic data was available for 988 patients. Of those, 215 (21.8%) were classified as 11q23/MLL+ after central cytogenetic review. The majority of patients with 11q23/MLL+ AML (n=200, 93%) were classified as intermediate risk (IR) and a minority (n=15, 7%) were classified as high risk (HR) based upon high FLT3 internal tandem duplication allelic ratio (FLT3-ITD-AR), monosomy 5/5q deletion, monosomy 7, or >15% blasts by morphology following Induction (Ind) I. HSCT was performed for 30 patients (14%).We defined 11q23/MLL+ subgroups for partners identified in ≥5 cases. Partners in <5 cases were grouped as "other"; unidentified fusions were classified as "unknown". Outcomes of minimal residual disease (MRD) at end of Ind I and complete remission (CR) at end of Ind II, 5-yr EFS and OS from study entry, and 5-yr RR from end of Ind II for patients in CR were compared across subgroups. Univariable and multivariable analyses were performed.Results: The median age for the 11q23/MLL+ cohort was 2.5 years and the distribution was equally male and female. The majority of cases (n=175, 81%) were classified into 8 specific partner subgroups, and the remaining cases were classified as other (n=30, 14%) or unknown (n=10, 5%). The most common translocation was t(9;11)(p22;q23) (n= 82, 38%). Central nervous system involvement was rare (<10% overall and in every subgroup). While extramedullary chloromas were rare (7% overall), chloromas were reported in 83% (n=5) of t(10;11)(p11.2;q23), 40% (n=16) of t(10;11)(p12;q23), and 27% (n=4) of t(6;11)(q27;q23). ACAs were observed in 86 of 211 cases (41%) that underwent central review. ACAs were numerical in 54 cases (26%), most commonly trisomy 8 (n=30, 14%) and structural + numerical in 32 cases (15%), most commonly involving chromosome 1 (n=11, 34%). Molecular findings for 3 studied genes were rare: High FLT3-ITD-AR n=4; NPM1 n=1; CEBPA n=0.Clinical outcomes varied significantly by fusion partner and poorer OS was primarily due to relapse (Table 1). CR rate was 86% overall and did not vary by subgroups. MRD was detected in 21% overall and was most common in t(1;11)(q21;q23) and t(6;11)(q27;q23). Complex karyotype (≥3 abnormalities) was seen in 52 cases (25%) and predicted inferior outcome compared to <3 abnormalities (5-yr EFS 29% vs. 41%, p=0.02; 5-yr OS 44% vs. 63%, p=0.001, respectively). Chromosome 1 abnormalities were associated with very poor outcomes, 5-yr EFS 19% and 5-yr OS 29%. The most unfavorable partners for EFS were t(6;11)(q27;q23), t(10;11)(p11.2;q23), t(10;11)(p12;q23), and t(11;19)(q23;p13.3)(Figure 1). In multivariable comparison to patients with t(9;11)(p22;q23), the former 3 groups maintained inferior EFS (HR 2.51, p=0.006; HR 3.10, p<0.001; HR 2.15, p=0.002, respectively) and OS (HR 2.56, p=0.017; HR 4.8, p=0.006; HR 2.14, p=0.016, respectively).Conclusions: Fusion partners critically impact the prognosis of 11q23/MLL+ AML. In this large, uniformly treated cohort, t(6;11)(q27;q23), t(10;11)(p11.2;q23) and t(10;11)(p12;q23) were independently associated with inferior EFS and OS. Children with these unfavorable partners are at high risk for relapse and allogeneic HSCT should be considered in first CR. Complex karyotype, chromosome 1 aberrations, and extramedullary chloromas were additional adverse prognostic factors. Work is ongoing to confirm these results in the subsequent COG trial, AAML1031. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.