Clinicopathologic features of epithelial ovarian carcinoma in younger vs. older patients: analysis in Japanese women

Objective

The purpose of this study was to clarify the clinical features of epithelial ovarian carcinoma (EOC) in younger vs. older patients in Japan.

Methods

We collected data on 1,562 patients with EOC treated at multiple institutions in the Tokai Ovarian Tumor Study Group, and analyzed them retrospectively. All patients were divided into 2 groups: group A (≤40 years old) and group B (>40 years old). The data were analyzed to evaluate prognostic factors and the distribution of features in each group. Patients were subjected to univariate and multivariate analyses to evaluate overall survival (OS).

Results

The median follow-up time was 45.1 months (range, 1 to 257 months). Patients in group A had a significantly higher rate of stage I disease (67.3% vs. 42.6%, respectively; p<0.001) and the mucinous type (36.7% vs. 13.5%, respectively; p<0.001) than those in group B. There was a significant difference of OS between the 2 groups (p=0.013). However, upon stratification according to the stage, there were no significant differences in the OS between the 2 groups (group A vs. B: stage I, p=0.533; stage II-IV, p=0.407). Multivariate analysis revealed that younger age was not an independent prognostic factor for OS.

Conclusion

On the basis of our data, younger patients had a different clinical profile than older patients, particularly regarding the stage of the disease and pathological distribution; however, they showed a similar long-term prognosis, even upon stratification according to the stage.     

Survival benefit of taxane plus platinum in recurrent ovarian cancer with non-clear cell,non-mucinous histology

Objective

This study was conducted to examine the effects of front-line chemotherapy on overall survival (OS) and postrecurrence survival (PRS) of patients with recurrent ovarian cancer, when stratifying the histologic type.

Methods

Five hundred and seventy-four patients with recurrent ovarian cancer with sufficient clinical information, including front-line chemotherapy, were analyzed. The pathologic slides were evaluated by central pathologic review. The patients were divided into two groups: group A (n=261), who underwent taxane plus platinum, and group B (n=313), who underwent conventional platinum-based chemotherapy without taxanes.

Results

The median age was 54 years (range, 14 to 89 years). Group A had significantly better median OS (45.0 months vs. 30.3 months, p<0.001) and PRS (23.0 months vs. 13.0 months, p<0.001) compared to group B. The OS and PRS were similar between the groups in patients with clear cell or mucinous histology. In contrast, among patients with non-clear cell, non-mucinous histologies, the OS and PRS of group A were significantly better than those of group B (OS, p<0.001; PRS, p<0.001). Multivariable analyses revealed that, among patients with non-clear cell, non-mucinous histologies, chemotherapy including taxane and platinum was an independent predictor of favorable survival outcomes. Conversely, in patients with clear cell or mucinous histology, taxane-including platinum-based combination chemotherapy did not improve the OS and PRS compared to a conventional platinum-based regimen which did not include taxanes.

Conclusion

Since the emergence of taxane plus platinum, the prognosis of patients with recurrent ovarian cancer has improved. However, we here demonstrate that this improvement is limited to patients with non-clear cell, non-mucinous histologies.     

Peritumoral Neuropilin-1 and VEGF receptor-2 expression increases time to recurrence in hepatocellular carcinoma patients undergoing curative hepatectomy

Purpose

To determined Neuropilin-1 (NRP-1) and vascular endothelial growth factor receptor 2 (VEGFR-2) expression in the tumoral and peritumoral tissues of 214 treatment-naïve HCC patients and its correlation with overall survival (OS) and time to recurrence (TTR).

Experimental Design

NRP-1 and VEGFR-2 expression were examined by tissue microarray and peritumoral hypoxia by pimonidazole staining and angiogenesis by microvessel density (MVD). OS and TTR were evaluated by Kaplan-Meier analysis and log-rank test.

Results

Peritumoral NRP-1 and VEGFR-2 expression were significantly higher than that of the tumoral tissue (p < 0.001 for both), and high peritumoral expression of both factors was negatively associated with tumor size (p < 0.001 for both). Patients with high peritumoral expression of both proteins had the longest median OS (>94.0 months) and TTR (>84.0 months). The multivariate Cox proportional hazards analysis revealed that patients with high peritumoral expression of both NRP-1 and VEGFR-2 were more than 4 times less likely to have recurrence (p = 0.004) and more than 10 times likely to survive (p < 0.001).

Conclusions

Peritumoral NRP-1 and VEGFR-2 expression is associated with prolonged TTR and extended OS of HCC patients and both may be useful as predictors of surgical outcome of HCC patients and explored as potential therapeutic targets.     

Clinical impact of post-progression survival on overall survival in patients with limited-stage disease small cell lung cancer after first-line chemoradiotherapy

Background

The effects of first-line chemoradiotherapy on overall survival (OS) may be confounded by subsequent lines of therapy in patients with limited-stage disease small cell lung cancer (LD-SCLC). Therefore, we aimed to determine the relationships between progression-free survival (PFS), post-progression survival (PPS) and OS after first-line chemoradiotherapy in LD-SCLC patients.

Patients and methods.

We retrospectively analyzed 71 LD-SCLC patients with performance status (PS) 0–2 who received first-line chemoradiotherapy and had disease recurrence between September 2002 and March 2013 at Shizuoka Cancer Center (Shizuoka, Japan). We determined the correlation between PFS and OS and between PPS and OS at the individual level. In addition, we performed univariate and multivariate analyses to identify significant prognostic factors of PPS.

Results

OS is more strongly correlated with PPS (Spearman’s r = 0.86, R² = 0.72, p < 0.05) than PFS (Spearman’s r = 0.46, R² = 0.38, p < 0.05). In addition, the response to second-line treatments, the presence of distant metastases at recurrence and the number of additional regimens after first-line chemoradiotherapy were significant independent prognostic factors for PPS.

Conclusions

PPS has more impact on OS than PFS in recurrent LD-SCLC patients with good PS at beginning of the treatment. Moreover, treatments administered after first-line chemoradiotherapy may affect their OS. However, larger multicenter studies are needed to validate these findings.     

Post-mastectomy radiotherapy benefits subgroups of breast cancer patients with T1–2 tumor and 1–3 axillary lymph node(s) metastasis

Background

To determine the role of postmastectomy radiotherapy (PMRT) in breast cancer patients with T1–2 and N1 disease.

Patients and methods.

A total of 207 postmastectomy women were enrolled. The 5-year Kaplan-Meier estimates of locoregional recurrence rate (LRR), distant recurrence rate (DRR) and overall survival (OS) were analyzed by different tumor characteristics. Multivariate analyses were performed using Cox proportional hazards modeling.

Results

With median follow-up 59.5 months, the 5-year LRR, DRR and OS were 9.1%, 20.3% and 84.4%, respectively. On univariate analysis, age < 40 years old (p = 0.003) and Her-2/neu over-expression (p = 0.016) were associated with higher LRR, whereas presence of LVI significantly predicted higher DRR (p = 0.026). Negative estrogen status (p = 0.033), Her-2/neu overexpression (p = 0.001) and LVI (p = 0.01) were significantly correlated with worse OS. PMRT didn’t prove to reduce 5-year LRR (p = 0.107), as well as 5-year OS (p = 0.918). In subgroup analysis, PMRT showed significant benefits of improvement LRR and OS in patients with positive LVI.

Conclusions

For patients with T1–2 and N1 stage breast cancer, PMRT can decrease locoregional recurrence and increase overall survival only in patients with lymphovascular invasion.     

Comparison of anal cancer outcomes in public and private hospital patients treated at a single radiation oncology center

Objective

To compare clinical and treatment characteristics and outcomes in locally advanced anal cancer, a potentially curable disease, in patients referred from a public or private hospital.

Methods

We retrospectively reviewed 112 anal cancer patients from a public and a private hospital who received definitive chemoradiotherapy at the same cancer center between 2004 and 2013. Tumor stage, radiotherapy delay, radiotherapy duration, and unplanned treatment breaks ≥10 days were compared using t-test and χ² test. Overall survival (OS), disease free survival (DFS), and colostomy free survival (CFS) were examined using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazard models for OS and DFS were developed.

Results

The follow-up was 14.9 months (range, 0.7-94.8 months). Public hospital patients presented with significantly higher clinical T stage (P<0.05) and clinical stage group (P<0.05), had significantly longer radiotherapy delays (P<0.05) and radiotherapy duration (P<0.05), and had more frequent radiation therapy (RT) breaks ≥10 days (P<0.05). Three-year OS showed a marked trend in favor of private hospital patients for 3-year OS (72.8% vs. 48.9%; P=0.171), 3-year DFS (66.3% vs. 42.7%, P=0.352), and 3-year CFS (86.4% vs. 68.9%, P=0.299). Referral hospital was not predictive of OS or DFS on multivariate analysis.

Conclusions

Public hospital patients presented at later stage and experienced more delays in initiating and completing radiotherapy, which may contribute to the trend in poorer DFS and OS. These findings emphasize the need for identifying clinical and treatment factors that contribute to decreased survival in low socioeconomic status (SES) populations.     

High CXC chemokine receptor 4 expression is an adverse prognostic factor in patients with clear-cell renal cell carcinoma

Background:

Aberrant CXC chemokine receptor 4 (CXCR4) expressions in malignant tissues have been reported; however, its role in kidney cancer prognosis remains unknown. The aim of this study was to determine the prognostic value of CXCR4 expression in patients with clear-cell renal cell carcinoma (ccRCC).

Methods:

The study included 225 patients with ccRCC. The cohort was split into a training set (n=125) and a validation set (n=100). CXC chemokine receptor 4 expression was analysed by immunohistochemical staining and its correlations with clinicopathologic features and prognosis were evaluated.

Results:

CXCR4-staining intensity increased gradually accompanied with disease progression from TNM stages I to IV in 225 patients with ccRCC. Moreover, high CXCR4 expression indicated reduced overall survival (OS) in the training (P<0.001) and validation (P<0.001) sets, especially for patients with early-stage (TNM stage I+II) diseases. Furthermore, CXCR4 expression was identified as an independent prognostic factor for OS, and combining TNM stage with CXCR4 expression showed a better prognostic value for OS in both sets.

Conclusions:

High CXCR4 expression, an independent adverse prognostic factor, could be combined with TNM stage to generate a predictive nomogram for clinical outcome in patients with ccRCC.     

Surveillance for asymptomatic recurrence in resected stage III colon cancer: does it result in a more favorable outcome?

Background

Evidence from dated and moderate quality trials supports a modest survival benefit for intensive surveillance in resected colon cancer (CC). This study evaluates surveillance in a modern population-based cohort of stage III CC patients (pts).

Methods

Records of pts who initiated oxaliplatin-based adjuvant chemotherapy (AC) for stage III CC between 2006-2011 at the British Columbia Cancer Agency (BCCA) were reviewed. Kaplan-Meier and log rank test were generated to investigate whether diagnosis of recurrence based on symptoms was associated with worse overall survival (OS). OS1 and OS2 were measured from date of recurrence or date of initial surgery, respectively.

Results

Of 635 pts who received AC for stage III CC, 175 pts (27.5%) recurred and 118 (18.6%) died at a median follow-up of 67.7 months. Recurrences were detected by surveillance in 149 pts (41% by CEA elevation and 44% by abnormal imaging), and symptoms in 26 pts (15%). Patients with surveillance-detected recurrences had a shorter median relapse-free survival (RFS) (18.5 vs. 25.3 months, HR 1.82, P<0.001), and longer median OS1 (28.5 vs. 6.5 months, HR 0.37, P<0.001). However, median OS2 was not significantly different (50.9 vs. 39.1 months, HR 0.66, P=0.091). Pts with surveillance-detected recurrence received more potentially curative metastasectomy (39% vs. 7%, P=0.002) and chemotherapy (70% vs. 50%, P=0.03).

Conclusions

In this modern population-based cohort study, the OS impact of detecting asymptomatic recurrences in stage III CC is unclear. However, pts with asymptomatic recurrences were more likely to receive potentially curative metastasectomy and chemotherapy.     

Critical weight loss is a major prognostic indicator for disease-specific survival in patients with head and neck cancer receiving radiotherapy

Background:

Pre-treatment weight loss (WL) is a prognostic indicator for overall survival (OS) in head and neck cancer (HNC) patients. This study investigates the association between WL before or during radiotherapy and disease-specific survival (DSS) in HNC patients.

Methods:

In 1340 newly diagnosed HNC patients, weight change was collected before and during (adjuvant) radiotherapy with curative intent. Critical WL during radiotherapy was defined as >5% WL during radiotherapy or >7.5% WL until week 12. Differences in 5-year OS and DSS between WL groups were analysed by Cox''s regression with adjustments for important socio-demographic and tumour-related confounders.

Results:

Before radiotherapy, 70% of patients had no WL, 16% had ⩽5% WL, 9% had >5–10% WL, and 5% had >10% WL. Five-year OS and DSS rates for these groups were 71%, 59%, 47%, and 42% (P<0.001), and 86%, 86%, 81%, and 71%, respectively (P<0.001). After adjustment for potential confounders, >10% WL before radiotherapy remained significantly associated with a worse OS (HR 1.7; 95% CI 1.2–2.5; P=0.002) and DSS (HR 2.1; 95% CI 1.2–3.5; P=0.007).The 5-year OS and DSS rates for patients with critical WL during radiotherapy were 62% and 82%, compared with 70% and 89% for patients without critical WL (P=0.01; P=0.001). After adjustment, critical WL during radiotherapy remained significantly associated with a worse DSS (HR 1.7; 95% CI 1.2–2.4; P=0.004).

Conclusion:

Weight loss both before and during radiotherapy are important prognostic indicators for 5-year DSS in HNC patients. Randomised studies into the prognostic effect of nutritional intervention are needed.     

The neutrophil–lymphocyte ratio and its utilisation for the management of cancer patients in early clinical trials

Background:

Inflammation is critical to the pathogenesis and progression of cancer, with a high neutrophil–lymphocyte ratio (NLR) associated with poor prognosis. The utility of studying NLR in early clinical trials is unknown.

Methods:

This retrospective study evaluated 1300 patients treated in phase 1 clinical trials between July 2004 and February 2014 at the Royal Marsden Hospital (RMH), UK. Data were collected on patient characteristics and baseline laboratory parameters.

Results:

The test cohort recruited 300 patients; 53% were female, 35% ECOG 0 and 64% ECOG 1. RMH score was 0–1 in 66% and 2–3 in 34%. The median NLR was 3.08 (IQR 2.06–4.49). Median OS for the NLR quartiles was 10.5 months for quartile-1, 10.3 months for quartile-2, 7.9 months for quartile-3 and 6.5 months for quartile-4 (P<0.0001). Univariate analysis identified RMH score (HR=0.55, P<0.0001), ECOG (HR=0.62, P=0.002) and neutrophils (HR=0.65, P=0.003) to be associated with OS. In multivariate analysis, adjusting for RMH score, ECOG, neutrophils and tumour type, NLR remained significantly associated with OS (P=0.002), with no association with therapeutic steroid use. These results were validated in a further 1000 cancer patients. In the validation cohort, NLR was able to discriminate for OS (P=0.004), as was the RMH score. This was further improved on in the RMH score+NLR50 and RMH score+Log₁₀NLR models, with an optimal NLR cutoff of 3.0.

Conclusions:

NLR is a validated independent prognostic factor for OS in patients treated in phase 1 trials. Combining the NLR with the RMH score improves the discriminating ability for OS.     

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:

Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.

Methods:

The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.

Results:

The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.

Conclusion:

This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.     

First-, second-, third-line therapy for mRCC: benchmarks for trial design from the IMDC

Background:

Limited data exist on outcomes for metastatic renal cell carcinoma (mRCC) patients treated with multiple lines of therapy. Benchmarks for survival are required for patient counselling and clinical trial design.

Methods:

Outcomes of mRCC patients from the International mRCC Database Consortium database treated with 1, 2, or 3+ lines of targeted therapy (TT) were compared by proportional hazards regression. Overall survival (OS) and progression-free survival (PFS) were calculated using different population inclusion criteria.

Results:

In total, 2705 patients were treated with TT of which 57% received only first-line TT, 27% received two lines of TT, and 16% received 3+ lines of TT. Overall survival of patients who received 1, 2, or 3+ lines of TT were 14.9, 21.0, and 39.2 months, respectively, from first-line TT (P<0.0001). On multivariable analysis, 2 lines and 3+ lines of therapy were each associated with better OS (HR=0.738 and 0.626, P<0.0001). Survival outcomes for the subgroups were as follows: for all patients, OS 20.9 months and PFS 7.2 months; for those similar to eligible patients in the first-line ADAPT trial, OS 14.7 months and PFS 5.6 months; for those similar to patients in first-line TIVO-1 trial, OS 24.8 months and PFS 8.2 months; for those similar to patients in second-line INTORSECT trial, OS 13.0 months and PFS 3.9 months; and for those similar to patients in the third-line GOLD trial, OS 18.0 months and PFS 4.4 months.

Conclusions:

Patients who are able to receive more lines of TT live longer. Survival benchmarks provide context and perspective when interpreting and designing clinical trials.     

Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing 18F-FDG PET/CT SUV quantification

Background

The purpose of the study was to evaluate the correlation between the maximum standardized uptake value (SUVmax), size of primary lung lesion, disease-free survival (DFS) and overall survival (OS) in patients with stage I and II non-small cell lung cancer (NSCLC) in 2 years follow-up.

Patients and methods.

Forty-nine patients with stage I–II NSCLC were included in this study. Pre-surgical 2-deoxy-2-[18F]fluoro-D-glucose positron-emission tomography (¹⁸F-FDG PET/CT) study was performed for all patients. The relationship between SUVmax, tumour size and clinical outcome was measured. The cut-off value for SUVmax and tumour size with the best prognostic significance, probability of DFS and the correlation between SUVmax and the response to therapy were calculated.

Results

There was a statistically significant correlation between SUVmax and DFS (p = 0.029). The optimal cut-offs were 9.00 for SUVmax (p = 0.0013) and 30mm for tumour size (p = 0.0028). Patients with SUVmax > 9 and primary lesion size > 30 mm had an expected 2years-DFS of 37.5%, while this rose to 90% if the tumour was <30 mm and/or SUVmax was <9.

Conclusions

In stage I-II, SUVmax and tumour size might be helpful to identify the subgroup of patients with high chance for recurrence.     

Prognostic relevance of acquired uniparental disomy in serous ovarian cancer

Background

Acquired uniparental disomy (aUPD) can lead to homozygosity for tumor suppressor genes or oncogenes. Our purpose is to determine the frequency and profile aUPD regions in serous ovarian cancer (SOC) and investigated the association of aUPD with clinical features and patient outcomes.

Methods

We analyzed single nucleotide polymorphism (SNP) array-based genotyping data on 532 SOC specimens from The Cancer Genome Atlas database to identify aUPD regions. Cox univariate regression and Cox multivariate proportional hazards analyses were performed for survival analysis.

Results

We found that 94.7% of SOC samples harbored aUPD; the most common aUPD regions were in chromosomes 17q (76.7%), 17p (39.7%), and 13q (38.3%). In Cox univariate regression analysis, two independent regions of aUPD on chromosome 17q (A and C), and whole-chromosome aUPD were associated with shorter overall survival (OS), and five regions on chromosome 17q (A, D-G) and BRCA1 were associated with recurrence-free survival time. In Cox multivariable proportional hazards analysis, whole-chromosome aUPD was associated with shorter OS. One region of aUPD on chromosome 22q (B) was associated with unilateral disease. A statistically significant association was found between aUPD at TP53 loci and homozygous mutation of TP53 (p < 0.0001).

Conclusions

aUPD is a common event and some recurrent loci are associated with a poor outcome for patients with serous ovarian cancer.

Electronic supplementary material

The online version of this article (doi:10.1186/s12943-015-0289-1) contains supplementary material, which is available to authorized users.     

Prospective evaluation of unmet needs of rural and aboriginal cancer survivors in Northern British Columbia

Background

The unmet needs of cancer survivors in rural, remote, and aboriginal communities are largely unexplored. We explored potential differences between rural survivors (rss) in 4 general population (gp) and 4 First Nations (fn) communities.

Methods

We approached 4 gp and 4 fn rs communities to participate in a mixed-methods project. Participants completed the Hospital Anxiety and Depression Scale (hads) and the Survivor Unmet Needs Survey (suns) and provided demographic information. Each question on the suns can be scored from 0 to 4, with 0 representing “no unmet need” and 4 representing “very high unmet need.” A directed approach to content analysis of focus group and interview data was used to triangulate the hads and suns results.

Results

We prospectively accrued 23 fn rss and 56 gp rss for this study. More fn rss had borderline or abnormal anxiety (5% vs. 21%, p = 0.02). Compared with gp rss, fn rss had higher unmet needs scores in all categories: Information (2.29 vs. 0.8, p < 0.001), Work and Financial (1.66 vs. 0.5, p < 0.001), Access and Continuity of Health Care (1.83 vs. 0.44, p < 0.001), Coping and Sharing (2.22 vs. 0.62, p < 0.001), and Emotional (2.12 vs. 0.63, p < 0.001). The qualitative findings provided examples and insight into the unmet needs experienced by rss.

Conclusions

First Nations rss had significantly higher anxiety and unmet needs compared with their gp rs counterparts. In addition, different qualitative themes were identified in the groups. Our findings support the development of tailored approaches to survivorship for these populations.     

A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer

Background:

PEP02, also known as MM-398, is a novel nanoliposomal irinotecan that has improved pharmacokinetics and tumour bio-distribution of the free drug. This phase 2 study evaluated PEP02 monotherapy as second-line treatment for pancreatic cancer.

Methods:

Patients who had metastatic pancreatic adenocarcinoma, Karnofsky performance status ⩾70, and had progressed following gemcitabine-based therapy were eligible. Intravenous injection of PEP02 120 mg m⁻² was given every 3 weeks. Simon 2-stage design was used. The primary objective was 3-month survival rate (OS_3-month).

Results:

A total of 40 patients were enrolled. The most common severe adverse events included neutropenia, abdominal pain, asthenia, and diarrhoea. Three patients (7.5%) achieved an objective response, with an additional 17 (42.5%) demonstrating stable disease for a minimum of two cycles. Ten (31.3%) of 32 patients with an elevated baseline CA19-9 had a >50% biomarker decline. The study met its primary end point with an OS_3-month of 75%, with median progression-free survival and overall survival of 2.4 and 5.2 months, respectively.

Conclusion:

PEP02 demonstrates moderate antitumour activity with a manageable side effect profile for metastatic, gemcitabine-refractory pancreatic cancer patients. Given the limited treatment options available to this patient population, a phase 3 trial of PEP02 (MM-398), referred to as NAPOLI-1, is currently underway.     

Dynamic-susceptibility contrast agent MRI measures of relative cerebral blood volume predict response to bevacizumab in recurrent high-grade glioma

Background

The anti-VEGF antibody, bevacizumab, is standard treatment for patients with recurrent glioblastoma. In this setting, traditional anatomic MRI methods such as post-contrast T1-weighted and T2-weighted imaging are proving unreliable for monitoring response. Here we evaluate the prognostic significance of pre- and posttreatment relative cerebral blood volume (rCBV) derived from dynamic susceptibility contrast MRI to predict response to bevacizumab.

Methods

Thirty-six participants with recurrent high-grade gliomas who underwent rCBV imaging 60 days before and 20–60 days after starting bevacizumab treatment were enrolled. Tumor regions of interest (ROIs) were determined from deltaT1 maps computed from the difference between standardized post and precontrast T1-weighted images. Both pre- and posttreatment rCBV maps were corrected for leakage and standardized (stdRCBV) to a consistent intensity scale. The Kaplan–Meier method was used to determine if either the pre- or post-bevacizumab stdRCBV within the tumor ROI was predictive of overall survival (OS) or progression free survival (PFS).

Results

The OS was significantly longer if either the pre- (380d vs 175d; P=.0024) or posttreatment stdRCBV (340d vs 186d; P = .0065) was <4400. The posttreatment stdRCBV was also predictive of PFS (167d vs 78d; P = .0006). When the stdRCBV values were both above versus both below threshold, the OS was significantly worse (100.5d vs 395d; P < .0001). With a 32.5% decrease in stdRCBV, the risk of death was reduced by about 68% but increased by 140% with a 29% increase in stdRCBV.

Conclusions

Standardized rCBV is predictive of OS and PFS in patients with recurrent high-grade brain tumor treated with bevacizumab.     

Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study

Purpose

The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed.

Methods

Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006.

Results

The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses).

Conclusion

Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.     

The influence of radiation therapy dose escalation on overall survival in unresectable pancreatic adenocarcinoma

Purpose

Radiation therapy (RT) dose escalation in unresectable pancreatic adenocarcinoma (PAC) remains investigational. We examined the association between total RT dose and overall survival (OS) in patients with unresectable PAC.

Methods and materials

National cancer data base (NCDB) data were obtained for patients who underwent definitive chemotherapy and RT (chemo-RT) for unresectable PAC. Univariate (UV) and multivariate (MV) survival analysis were performed along with Kaplan-Meier (KM) estimates for incremental RT dose levels.

Results

A total of 977 analyzable patients met inclusion criteria. Median tumor size was 4.0 cm (0.3-40 cm) and median RT dose was 45 Gy. Median OS was 10 months (95% CI, 9-10 months). On MV analysis RT dose <30 Gy [HR, 2.38 (95% CI, 1.85-3.07); P<0.001] and RT dose ≥30 to <40 Gy [HR, 1.41 (95% CI, 1.04-1.91); P=0.026] were associated with lower OS when compared with dose ≥55 Gy. Patients receiving RT doses from 40 to <45, 45 to <50, 50 to <55, and ≥55 Gy did not differ in OS.

Conclusions

Lack of benefit to OS with conventionally delivered RT above 40 Gy is shown. Optimal RT dose escalation methods in unresectable PAC remain an important subject for investigation in prospective clinical trials.