Adverse Pathologic Factors Research Articles

Indications for Adjuvant Radiation after Radical Prostatectomy as Predicted by Artificial Intelligence-Derived Dominant Intraprostatic Lesion Volume.

In prostate cancer, PI-RADs scores of dominant intraprostatic lesions (DILs) in multi-parametric magnetic resonance imaging (mpMRI) are prognostic; however, their inter-observer agreement is only moderate. Artificial intelligence (AI) may be a powerful tool for prognostication by analyzing a large number of scans consistently in a short amount of time. This study investigated whether the DIL volume (DILvol) provided by an AI deep-learning segmentation algorithm could predict adverse findings at radical prostatectomy (RP), some of which could warrant adjuvant radiation therapy (RT). We conducted a retrospective study of 185 consecutive patients with localized prostate cancer who underwent an endorectal coil, high B-value (> = 1000 s/mm2), 3-Tesla mpMRI followed by RP between 2015 and 2017. Using a previously trained deep learning nnUNet algorithm for providing DIL segmentations from patients treated with definitive RT, we segmented the DIL for the RP cohort. We evaluated the association of AI DILvol with the risks of adverse pathologic factors, including positive margins, pathologic T3 (pT3) disease, and pathologic Gleason (pGS8-10) disease, using separate univariate logistic regression models. We then included AI DILvol, pT3 (vs pT2), pGS8-10 (vs pGS6-7), margin status, and pre-RP PSA for predicting post-RP PSA values utilizing multivariate linear regression analysis. Finally, we included these same factors into a multivariate logistic regression analysis for predicting the risk of meeting adjuvant RT indications (PSA persistence post-RP > = 0.1 ng/mL or positive lymph nodes). The median time between RP and post-PSA value was 1.6 months. The Pearson's correlation coefficient between AI and reference DILvol (sum of manually contoured PI-RADS 3-5 lesions) was 0.86 (p < 0.001). The Pearson's correlation coefficient between AI DILvol and pathologic tumor size was 0.63 (p < 0.001). Utilizing separate univariate logistic regression models, we found that AI DILvol was significantly associated with the risks of positive margins (OR 1.31 [1.10, 1.58]; p = 0.003), pT3 (OR 1.59 [95% CI: 1.30, 1.99]; p < 0.001), and pGS8-10 (OR 1.28 [1.07, 1.56]; p = 0.01). On multivariate linear regression, AI DILvol (0.27/mL [0.25, 0.29]; p < 0.001) was significantly correlated with post-RP PSA values, after controlling for adverse factors and pre-RP PSA. On multivariate logistic regression, AI DILvol (adjusted OR 1.32 [1.05, 1.69]; p = 0.03) was the only factor significantly associated with the risk of meeting adjuvant RT indications after controlling for these same factors. For localized prostate cancer treated with RP, AI DILvol was the only factor significantly associated with the risk of meeting adjuvant RT indications, even after controlling for pathologic factors at RP. Further studies are needed to determine if AI DILvol is prognostic for long-term oncologic outcomes after RP.

Radiotherapy for Meningioma.

Meningiomas are the most common primary intracranial brain tumor, and have a heterogeneous biology and an unmet need for targeted treatment options. Existing treatments for meningiomas are limited to surgery, radiotherapy, or a combination of these depending on clinical and histopathological features. Treatment recommendations for meningioma patients take into consideration radiologic features, tumor size and location, and medical comorbidities, all of which may influence the ability to undergo complete resection. Ultimately, outcomes for meningioma patients are dictated by extent of resection and histopathologic factors, such as World Health Organization (WHO) grade and proliferation index. Radiotherapy is a critical component of meningioma treatment as either a definitive intervention using stereotactic radiosurgery or external beam radiotherapy, or in the adjuvant setting for residual disease or for adverse pathologic factors, such as high WHO grade. In this chapter, we provide a comprehensive review of radiotherapy treatment modalities, therapeutic considerations, radiation planning, and clinical outcomes for meningioma patients.

Development and validation of a vascularity-based architectural classification for clear cell renal cell carcinoma: correlation with conventional pathological prognostic factors, gene expression patterns, and clinical outcomes

AbstractThe prognostic significance of an architectural grading system for clear cell renal cell carcinoma (ccRCC) has recently been demonstrated. The present study aimed to establish a vascularity-based architectural classification using the cohort of 436 patients with localized ccRCC who underwent extirpative surgery and correlated the findings with conventional pathologic factors, gene expression, and prognosis. First, we assessed architectural patterns in the highest-grade area on hematoxylin and eosin-stained slides, then separately evaluated our surrogate score for vascularity. We grouped nine architectural patterns into three categories based on the vascular network score. “Vascularity-based architectural classification” was defined: category 1: characterized by enrichment of the vascular network, including compact/small nested, macrocyst/microcystic, and tubular/acinar patterns; category 2: characterized by a widely spaced-out vascular network, including alveolar/large nested, thick trabecular/insular, papillary/pseudopapillary patterns; category 3: characterized by scattered vascularity without a vascular network, including solid sheets, rhabdoid and sarcomatoid patterns. Adverse pathological prognostic factors such as TNM stage, WHO/ISUP grade, and necrosis were significantly associated with category 3, followed by category 2 (all p < 0.001). We successfully validated the classification using The Cancer Genome Atlas (TCGA) cohort (n = 162), and RNA-sequencing data available from TCGA showed that the angiogenesis gene signature was significantly enriched in category 1 compared to categories 2 and 3, whereas the immune gene signature was significantly enriched in category 3 compared to categories 1 and 2. In univariate analysis, vascularity-based architectural classification showed the best accuracy in pathological prognostic factors for predicting recurrence-free survival (c-index = 0.786). The predictive accuracy of our model which integrated WHO/ISUP grade, necrosis, TNM stage, and vascularity-based architectural classification was greater than conventional risk models (c-index = 0.871 vs. 0.755–0.843). Our findings suggest that the vascularity-based architectural classification is prognostically useful and may help stratify patients appropriately for management based on their likelihood of post-surgical recurrence.

Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.

New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC). To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45. In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1copy/mL by POD 1 (n=8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350copies/mL) and remained elevated until adjuvant treatment (n=3/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2-58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n=9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1mm (P=.0481) and with increasing lymph nodes involved (P=.0453) and were further associated with adjuvant treatment received (P=.0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2months earlier than clinical detection. POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery. This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC. We found that ctHPVDNA levels 1day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.

Immediate breast reconstruction has no impact on the oncologic outcomes of patients treated with post-mastectomy radiation therapy: a comparative analysis based on propensity score matching.

To investigate the impact of immediate breast reconstruction (iBR) on patients treated with post-mastectomy radiation therapy (PMRT) using propensity score matching (PSM). After a retrospective review of patients treated with PMRT between 2008 and 2017, we included 153 patients who underwent iBR and 872 patients who did not undergo iBR. Among the 153 patients who underwent iBR, 34 received one-stage iBR with autologous tissue and 119 received two-stage iBR. Conventional fractionated PMRT with a total dose of 50-50.4Gy in 25-28 fractions was performed in all patients. Propensity scores were calculated via logistic regression. Patients who underwent iBR were younger, had early stage disease, and had more frequent hormone receptor-positive tumor than those who did not undergo iBR. After PSM, 127 patients from each group with well-balanced characteristics were selected. With a median follow-up of 67.5months, iBR led to better 6-year disease-free survival rates compared to no iBR before PSM (84.8% vs. 71.4%, p = 0.003); after PSM, there was no significant difference (84.8% vs. 75.5%, p = 0.130). On multivariable analysis in the matched cohort, iBR was not associated with inferior disease-free survival (hazard ratio, 0.67; p = 0.175). In the sensitivity analysis, iBR was not associated with a lower disease-free survival across all prognostic groups. The 5-year cumulative incidence of iBR failure was 15.0%. In patients with adverse pathologic factors planning to receive PMRT, iBR did not compromise oncologic outcomes. In addition, iBR can be considered in patients treated with PMRT with several clinicopathologic risk factors.

Comparative analysis of quality of life for three different adjuvant treatment modality in early stage cervical cancer: an analysis from STARS study

<h3>Objectives:</h3> This analysis aimed to compare the quality of life (QoL) of patients with different adjuvant treatment modalities in STARS study for cervical cancer. <h3>Methods:</h3> QoL assessment was done at the baseline and then longitudinally after completing of radiation or chemotherapy assigned in STARS study. In the study, post-operative FIGO stage IB to IIA cervical cancer patients with adverse pathological factors were randomized in 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation weekly cisplatin or sequential chemoradiation (with cisplatin plus paclitaxel in 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy respectively). QoL was assessed with EORTC QLQ-C30 questionnaires at baseline (1 week after the surgery), during the treatment period (in the 5th week receiving pelvic irradiation), 12 months and 24 months after the completion of treatment. Analysis of variance by one-way repeated measures analyses of variance (ANOVA) was used to compare differences in QoL measures among treatment groups. <h3>Results:</h3> Totally, 816, 633, 360 and 254 patients had completed QoL assessment at baseline, during treatment period, 12 month and 24 month after the completion of treatment. At baseline, a lowest global health status (GH) and functional dimensions including physical, emotional, role, cognitive and social functioning, and lowest scores of symptom and single item scales were presented among the 3 groups with balance (p > 0.05). During treatment period, GH and other functional dimension scores were elevated, with symptom item scores declined in RT group. While in CCRT or SCRT group, an elevated scores of symptom scales including of nausea and vomiting (30.93±25.5 vs 20.8±25.0 in SCRT group, 31.0±28.1 vs 16.5±24.3 in CCRT group), and appetite loss (39.6±30.9 vs 34.8±32.1 in CCRT group) was noted when comparing with that in baseline. The score of item concerning financial difficult declined in CCRT and SCRT group, which was similar as RT group. The scores of GH, functional dimensions and other symptom scales were not different compared with baseline in these two groups. During treatment period, a highest score of global health, functional dimensions including physical, role, cognitive, social functioning, and lowest scores of symptom including fatigue, nausea and vomit, insomnia, appetite loss, constipation and diarrhea was presented in the RT group than the other two groups (GH score 66.5±16.4 in RT group, 60.7±17.9 in CCRT group and 61.9±17.5 in SCRT group, p=0.001). No differences between CCRT and SCRT group regarding GH, functional dimensions and symptom scores. In 12 and 24 months after the completion of treatments, further improved GH, functional dimension scores and declined symptom scores were observed in the whole population, with no significant differences among the 3 treatment groups. <h3>Conclusions:</h3> In CCRT and SCRT group, adding chemotherapy in adjuvant treatment had negative effects on GH, physical, cognitive, social and role function, as well as symptoms related to QoL during the treatment period compared with RT. While the symptoms resolved, functioning and general QoL improved after 12 months of treatment, indicating a transient impact on QoL of patients receiving adjuvant treatment.

Tumor Volume Predicts High-Risk Patients and Guides Initial Chemoradiotherapy for Early Cervical Cancer.

We evaluated the relationship between the minimum tumor-free margin, tumor volume, and adverse pathological risk factors in early cervical cancer and explored the predictive value of these parameters for different types of risk patients to guide individualized therapeutic strategies. Patients who received the initial treatment of radical operation of cervical cancer and their postoperative pathological reports in our hospital from July 1, 2017, to June 30, 2019, were reviewed. Their minimum tumor-free margin and tumor volume were measured on preoperative magnetic resonance imaging. Student’s t-test and the receiver operating characteristic curve analysis were used for data analysis. A total of 240 patients were included. Adverse pathological risk factors were as follows: deep cervical infiltration, 95 (39.6%) cases; lymph vascular space invasion, 91 (37.9%); lymph node metastasis, 20 (8.3%); parametrial infiltration, 8 (3.3%); tumor diameter ≥4 cm, 7 (2.9%); and positive surgical margin, 1 (0.4%). According to the adverse pathological factors, there were 20 (8.3%) high-risk patients, 50 (20.8%) medium-risk patients, and 170 (70.8%) low-risk patients. The ranges of the minimum tumor-free margin and tumor volume were 0.01–13.5 mm and 105–27,990 mm3, respectively. The minimum tumor-free margin with lymph node metastasis was significantly smaller than that without (P <0.05). The tumor volume with parametrial infiltration, deep cervical infiltration, or lymph vascular space invasion was significantly greater than that without (P < 0.05). The tumor volume was significantly different among low-, medium-, and high-risk patients (P <0.05). Tumor volume was of predictive value for high-risk patients (P < 0.05). With 3,505 mm3 as the cutoff value, the sensitivity and specificity for the prediction of high-risk patients were 88.9% and 84.8%, respectively. Tumor volume can be used as a great predictor of high-risk patients (cutoff value, 3,505 mm3), which could be an indication of initial chemoradiotherapy for early cervical cancer.

Comprehensive analysis of mutational and clinicopathologic characteristics of poorly differentiated colorectal neuroendocrine carcinomas

Poorly differentiated neuroendocrine carcinoma (NEC) is a rare subtype of colorectal cancer (CRC). This study aimed to investigate clinicopathologic characteristics of colorectal NECs and elucidate genomic differences and similarities between colorectal NECs and colorectal adenocarcinomas (ACs). A total of 30 colorectal NECs were screened for frequently identified CRC oncogenic driver genes by targeted next-generation sequencing of 382 genes. The median age of the patients was 67 years (range, 44 to 88 years). NECs occurred predominantly in the rectum (47%) and exhibited multiple adverse prognostic pathologic factors, including frequent lymphatic and vascular invasions, high rates of lymph node metastasis and distant metastasis and advanced TNM stage. The 1-, 3-, and 5-year overall survival rates of NEC patients were 46.7%, 36.4%, and 32.7%, respectively, with a median overall survival period of 11.5 months. In a molecular analysis, NECs showed high rates of BRAF mutation (23%), predominantly p.V600E (71%), and alterations in RB1 (47%), particularly deletion (57%). The frequencies and distributions of other genes, such as KRAS, APC, SMAD4, and PIK3CA, and microsatellite instability status were similar to those of ACs. These findings provide beneficial information for selecting therapeutic options, including targeted therapy, and a better understanding of the histogenesis of this tumour.

Neoadjuvant chemoradiotherapy with capecitabine in locally advanced rectal cancer: Analysis of prognostic factors.

92 Background: Capecitabine-based neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer (LARC). The objective of this retrospective study is to analyze overall survival (OS), local relapse free-survival (LRFS), distant metastases free-survival (DMFS) and prognostic factors. Methods: Between 2009 and 2018, 207 patients(p) with LARC has been treated in our hospital with neoadjuvant CRT. Clinical characteristics: Mean age: 65 y (41-87); male:129, female:78; TNM: cT2: 12p, cT3: 176p, cT4: 19p, cN0: 59p, cN1: 106p, cN2: 42p. Treatment: pelvic radiotherapy (45Gy, 1.8Gy/day) plus concomitant capecitabine (852mg/sqm/12h for 28 days). Surgery (mesorectal excision) was carried out 6-8 after the end of CRT. Statistics:Kaplan-Meier and Log-rank test. Results: Mean follow-up: 43 months. Downstaging:104/192 (54%). Pathological complete response:31/192 (16%). Sphincter preservation rate was 82%. Five-year OS, LRFS and DMFS were 89.9%, 93.3% and 81.7%, respectively. Factors predicting shorter 5-y OS were: cT4 (69% vs 91% and 91% for cT1 and CT2, respectively; p=0.027), pT3-4 (85% and 64% vs 100%, 100% and 98% for pT0, pT1 and pT2, respectively; p=0.008), pathological involved nodes (pN+) (77% vs 96%; p=0.001), perineural invasion (PNI) (78% vs 95%; p=0.041), LVI (p&lt;0.001), Ryan 3 (p&lt;0.001), resection margin R1 (67% vs 94% for R0; p&lt;0.001), no pCR (p=0.027) and absence of downstaging (73% vs 97%; p=0.001). Factors associated with poor 5-y DMFS were:pT3-4 ( 70% and 0% vs 96%,88% and 98% for pT0,pT1 and pT2, respectively; p&lt;0.001), pN+ (68% vs 88% for pN0: p&lt;0.001), PNI (64% vs 85%; p=0.036), Ryan 3 (49% vs 96%, 85% and 85% for Ryan 0, 1 and 2, respectively; p&lt;0.001), R1 (33% vs 86% for R0; p&lt;0.001) and absence of downstaging (50% vs 71%; p&lt;0.001). CTCAE 4.0 grade 3 toxicity: 1%. No grade 4 toxicity was seen. Conclusions: CRT with capecitabine provides high rates of survival and sphinter preservation with excellent tolerance. Patients with adverse pathological factors (pT4, pN+, PNI, Ryan 3, R1 and absence of downstaging) have a higher risk of distant metastasis and are more likely to benefit from adjuvant chemotherapy.

Effectiveness of Sequential Chemoradiation vs Concurrent Chemoradiation or Radiation Alone in Adjuvant Treatment After Hysterectomy for Cervical Cancer

There is no current consensus on the role of chemotherapy in addition to radiation for postoperative adjuvant treatment of patients with early-stage cervical cancer with adverse pathological factors. To evaluate the clinical benefits of sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT) compared with radiation alone (RT) as a postoperative adjuvant treatment in early-stage cervical cancer. After radical hysterectomy at 1 of 8 participating hospitals in China, patients with FIGO (International Federation of Gynecology and Obstetrics) stage IB to IIA cervical cancer with adverse pathological factors were randomized 1:1:1 to receive adjuvant RT, CCRT, or SCRT. Data were collected from February 2008 to December 2018. Patients received adjuvant RT (total dose, 45-50 Gy), CCRT (weekly cisplatin, 30-40 mg/m2), or SCRT (cisplatin, 60-75 mg/m2, plus paclitaxel, 135-175 mg/m2) in a 21-day cycle, given 2 cycles before and 2 cycles after radiotherapy, respectively. The primary end point was the rate of disease-free survival (DFS) at 3 years. A total of 1048 women (median [range] age, 48 [23-65] years) were included in the analysis (350 in the RT group, 345 in the CCRT group, and 353 in the SCRT group). Baseline demographic and disease characteristics were balanced among the treatment groups except that the rate of lymph node involvement was lowest in the RT group (18.3%). In the intention-to-treat population, SCRT was associated with a higher rate of DFS than RT (3-year rate, 90.0% vs 82.0%; hazard ratio [HR], 0.52; 95% CI, 0.35-0.76) and CCRT (90.0% vs 85.0%; HR, 0.65; 95% CI, 0.44-0.96). Treatment with SCRT also decreased cancer death risk compared with RT (5-year rate, 92.0% vs 88.0%; HR, 0.58; 95% CI, 0.35-0.95) after adjustment for lymph node involvement. However, neither DFS nor cancer death risk was different among patients treated with CCRT or RT. In this randomized clinical trial, conducted in a postoperative adjuvant treatment setting, SCRT, rather than CCRT, resulted in a higher DFS and lower risk of cancer death than RT among women with early-stage cervical cancer. ClinicalTrials.gov Identifier: NCT00806117.

Survival after minimally invasive surgery in early cervical cancer: is the intra-uterine manipulator to blame?

ObjectivesMinimally invasive radical hysterectomy is associated with decreased survival in patients with early cervical cancer. The objective of this study was to determine whether the use of an intra-uterine manipulator...

HSP90 expression and early recurrence in gastroenteropancreatic neuroendocrine tumors: Potential for a novel therapeutic target

BackgroundHeat shock protein (HSP)-90 promotes tumor growth and is overexpressed in many malignancies. HSP90 expression profile and its potential as a therapeutic target in primary and metastatic neuroendocrine tumors (NETs) are not known. MethodsHSP90 cytoplasmic expression and Ki-67 index were re-reviewed and scored by a pathologist blinded to all other clinicopathologic variables for patients who underwent resection of primary and metastatic gastroenteropancreatic (GEP) neuroendocrine tumors at a single institution (2000–2013). Primary outcome was recurrence-free survival (RFS). ResultsOf 263 tumors reviewed, 73% (n = 191) were primary GEP NETs, and 12% (n = 31) were NET liver metastases. Of the primary GEP-NETs, mean age was 56 years, 42% were male; 53% (n = 103) were pancreatic and 23% (n = 44) were small bowel. HSP90 expression was high in 34% (n = 64) and low in 66% (n = 127). Compared to low expression, high HSP90 was associated with advanced T-stage (T3/T4) (47 vs 27%; p = 0.02). Among patients who underwent curative-intent resections for primary, non-metastatic NETs (n = 145), high HSP90 was independently associated with worse RFS (HR 5.09, 95% CI 1.65–15.74; p = 0.005), after accounting for positive margin, LN involvement, increased tumor size, site of primary tumor, and Ki-67. When assessing NET liver metastases, 13% (n = 4) had high HSP90 expression and 87% (n = 26) had low expression. Patients with liver metastases with high HSP90 tended to have worse 1- and 3-year progression-free survival (25%, 25%) compared to those with low HSP90 (69%, 49%; p = 0.059). ConclusionHSP90 exhibits differential expression in resected GEP-NETs and liver metastases. High cytoplasmic expression is associated with early disease recurrence, even after accounting for other adverse pathologic factors. HSP90 inhibition may be a potential therapeutic target for neuroendocrine tumors.

Three-tiered Subclassification System of High-risk Prostate Cancer in Men Managed With Radical Prostatectomy: Implications for Treatment Decision-making

To inform treatment decisions for patients with high-risk prostate cancer (PCa), we determined rates of adverse pathologic factors and overall survival (OS) among subgroups of high-risk men. Using the National Cancer Database, 89,450 patients with clinical N0M0 unfavorable intermediate-risk, favorable high-risk (cT1c, Gleason 6, prostate-specific antigen [PSA] > 20 ng/mL or cT1c, biopsy Gleason 8, PSA < 10 ng/mL), standard high-risk (all other cT3a, biopsy Gleason ≥ 8, or PSA > 20 ng/mL), or very high-risk (cT3b-T4 or biopsy primary Gleason pattern 5) PCa treated with radical prostatectomy were identified. Rates of adverse pathologic factors (positive surgical margins, T4 disease, or pathologic lymph node involvement) were compared across subgroups. Patients with unfavorable intermediate-risk (n=31,381) and favorable high-risk (n=10,296) disease had similar rates of adverse features (7.6% vs 8.2%, adjusted odds ratio 1.00, 95% confidence interval 0.92-1.08, P= .974). Patients with standard high-risk (n=30,260) or very high-risk (n=7513) disease were significantly more likely to have adverse pathologic factors (15.9% and 26.5%, P < .001 for both). Patients with unfavorable intermediate-risk and favorable high-risk disease had similar 5-year OS (95.7% vs 95.1%, adjusted hazard ratio 1.06, 95% confidence interval 0.92-1.21, P = .411) but better OS compared to standard and very high-risk patients (93.4% and 88.1%, respectively; P < .001). Unfavorable intermediate-risk or favorable high-risk PCa patients had low rates of adverse pathologic factors and similar OS. In contrast, standard and very high-risk PCa patients had significantly higher rates of adverse pathologic factors and worse OS. This 3-tiered subclassification of high-risk disease may allow for improved treatment selection among patients considering surgery.

Sequential chemoradiation versus radiation alone or concurrent chemoradiation in adjuvant treatment after radical hysterectomy for stage IB1-IIA2 cervical cancer (STARS Study): A randomized, controlled, open-label, phase III trial.

6007 Background: There are limited data from previous studies regarding whether the addition of chemotherapy to adjuvant radiation after radical surgery improves outcomes among patients with early-stage cervical cancer and adverse pathological factors. Methods: This was a prospective randomized trial including patients with FIGO 2009 stage IB1-IIA2 cervical cancer and squamous-cell, adenocarcinoma, or adenosquamous carcinoma with at least one adverse factor after radical hysterectomy. Patients were randomized 1:1:1 to receive adjuvant radiation alone, concurrent chemoradiation with weekly cisplatin (30-40 mg/m2), or sequential chemoradiation with cisplatin (60-75 mg/m2) plus paclitaxel (135-175 mg/m2) in 21 day cycles, given 2 cycles before and 2 cycles after radiotherapy respectively. The primary outcome was the rate of disease-free survival at 3 years. Results: A total of 1,048 patients were included in the study (350, radiation alone; 345, concurrent chemoradiation; and 353, sequential chemoradiation). Overall, the median follow-up was 56 months and the median age of patients was 48 years. Most patients (75%) had stage IB1 or IIA1 disease. The three groups were similar with respect to histologic subtypes, the rate of lymphovascular invasion, parametrial, surgical margin and deep stromal involvement, tumor grade, rate of use of minimally invasive surgery, and neoadjuvant chemotherapy, except for lymph-node involvement that was lowest in radiation alone arm. In the intention-to-treat population, sequential chemoradiation was associated with a higher rate of disease-free survival than radiation alone (3-year rate, 90·0% vs. 82·0%; HR 0·52; 95% CI, 0·35 to 0·76) and concurrent chemoradiation (90·0% vs. 85·0%; HR 0·65; 95% CI, 0·44 to 0·96), differences remained after adjustment for lymph-node involvement. Sequential chemoradiation was also associated with a higher rate of overall survival than radiation alone (5-year rate, 92·0% vs. 88·0%; HR for death from cancer, 0·58; 95% CI, 0·35 to 0·95). However, neither disease-free survival nor cancer death risk was different between patients treated with concurrent chemoradiation or radiation alone. Conclusions: In this trial, sequential chemoradiation, rather than concurrent chemoradiation, resulted in a higher disease-free survival and lower risk of cancer death than radiation alone among women with early-stage cervical cancer after radical surgery. Clinical trial information: NCT00806117.

Differences in outcome for patients with cholangiocarcinoma: Racial/ethnic disparity or socioeconomic factors?

BackgroundInequities in cancer survival are well documented. Whether disparities in overall survival (OS) result from inherent racial differences in underlying disease biology or socioeconomic factors (SEF) is not known. Our aim was to define the association of race/ethnicity and SEF with OS in pts with cholangiocarcinoma (CCA). MethodsPatients with CCA of all sites and stages in the National Cancer Data Base (2004-13) were included. Racial/ethnic groups were defined as non-Hispanic White (NH-W), non-Hispanic Black (NH-B), Asian, and Hispanic. Income and education were based on census data for patients’ zip code. Income was defined as high (≥$63,000) vs low (<$63,000). Primary outcome was OS. Results27,151 patients were included with a mean age of 68 yrs; 51% were male. 78% were NH-W, 8% NH-B, 8% Hispanic, and 6% Asian. 56% had Medicare, 33% private insurance, 7% Medicaid, and 4% were uninsured. 67% had low income. 19% lived in an area where >20% of adults did not finish high school.NH-B and Hispanic patients had more unfavorable SEF including uninsured status, low income, and less formal education than NH-W and Asian pts (all p < 0.001). They were also younger, more likely to be female and to have metastatic disease (all p < 0.001). Despite this, NH-B race and Hispanic ethnicity were not associated with decreased OS. Male sex, older age, non-private insurance, low income, lower education, non-academic facility, location outside the Northeast, higher Charlson-Deyo score, worse grade, larger tumor size, and higher stage were all associated with decreased OS (all p < 0.001). On MV analysis, along with adverse pathologic factors, type of insurance (p = 0.003), low income (p < 0.001), and facility type and location of treatment (p < 0.001) remained associated with decreased OS; non-white race/ethnicity was not. ConclusionsDisparities in survival exist in CCA, however they are not driven by race/ethnicity. Non-privately insured and low-income patients had decreased OS, as did patients treated at non-academic centers and outside the Northeast. This suggests that decreased ability to access and afford care results in worse outcomes, rather than biological differences amongst racial/ethnic groups.

Breast cancer in young black women.

Young age at breast cancer diagnosis is associated with negative prognostic outcomes, and breast cancer in black women often manifests at a young age. This study evaluated the effect of age on breast cancer management and outcomes in black women. This was a retrospective cohort study of all black women treated for invasive breast cancer between 2005 and 2010 at a specialized tertiary-care cancer centre. Clinical and treatment characteristics were compared by age. Kaplan-Meier methodology was used to estimate overall survival (OS) and disease-free survival (DFS). A total of 666 black women were identified. Median BMI was 30 (range 17-56) kg/m2 and median tumour size was 16 (1-155) mm. Most tumours were oestrogen receptor-positive (66·4 per cent). Women were stratified by age: less than 40 years (74, 11·1 per cent) versus 40 years or more (592, 88·9 per cent). Younger women were significantly more likely to have a mastectomy, axillary lymph node dissection and to receive chemotherapy, and were more likely to have lymphovascular invasion and positive lymph nodes, than older women. The 5-year OS rate was 88·0 (95 per cent c.i. 86·0 to 91·0) per cent and the 5-year DFS rate was 82·0 (79·0 to 85·0) per cent. There was no statistically significant difference in OS by age (P = 0·236). Although DFS was inferior in younger women on univariable analysis (71 versus 88 per cent; P < 0·001), no association was found with age on multivariable analysis. Young black women with breast cancer had more adverse pathological factors, received more aggressive treatment, and had worse DFS on univariable analysis. Young age at diagnosis was, however, not an independent predictor of outcome.

The impact of intraoperative pancreatic resection margin status on prognosis of patients with pancreatic head cancer

Objective To study the impact of intraoperative pancreatic resection margin status on prognosis in patients with pancreatic head cancer. Methods The clinical and follow-up data of 109 patients who underwent pancreaticoduodenectomy at Ningbo Lihuili Hospital from March 2012 to October 2018 were analyzed retrospectively. The association of intraoperative resection margin status and other clinicopathological factors on prognosis was analyzed by the Kaplan-Meier method and the Cox proportional hazard model. Logistic multivariate analysis was used to study factors influencing the margin status. Results Of 109 patients, 20 had a positive intraoperative resection margin, and 89 had a negative margin. Postoperative pathological examination showed that all the patients had a negative surgical margin. Univariate analysis suggested that CA19-9 before operation, preoperative adjuvant chemotherapy, intraoperative pancreatic resection margin status, maximum diameter of tumor, perineural invasion, lymphovascular invasion, tumor differentiation, and N staging were significantly related to survival in the entire cohort (all P 0.05). Analysis of the clinicopathological factors between the two groups showed that in the positive pancreatic neck margin group, the distribution of adverse pathologic factors like low tumor differentiation, tumor diameter ≥4 cm, perineural invasion and lymphovascular invasion were significantly different compared with the negative group (P<0.05). Tumor diameter ≥4 cm (OR=5.72, 95%CI: 1.60~20.49) and low tumor differentiation (OR=3.79, 95%CI: 1.20~11.95) were independent influencing factors of positive margin on logistic multivariate analysis. Conclusions Intraoperative pancreatic positive margin was not an independent risk factor of prognosis, but it was meaningful in predicting survival. Presence of positive margins was often combined with existence of some adverse pathological features, such as large tumor diameter and low tumor differentiation. Prognosis of patients with a positive margin was often poor. A positive pancreatic margin was an intraoperative marker of poor tumor biology in patients with pancreatic ductal adenocarcinoma. Key words: Pancreatic neoplasms; Positive margin; Pancreaticoduodenectomy; Prognosis

STAT3 Inhibition for Gastroenteropancreatic Neuroendocrine Tumors: Potential for a New Therapeutic Target?

BackgroundGastroenteropancreatic neuroendocrine tumors (GEP-NETs) are highly vascular neoplasms treated similarly, irrespective of tumor location. The expression of pro-angiogenic factors (STAT3, VEGF, and HIF-1α) and their association with adverse pathologic factors and disease recurrence following resection remains unclear. MethodsAll patients with non-metastatic GEP-NETs who underwent curative-intent resection from 2000 to 2013 were included. Immunohistochemistry was performed for pro-angiogenic factors, Ki-67 index, and CD31 using tissue microarrays made in triplicate by a pathologist blinded to other clinicopathologic variables. Primary outcome was a 3-year recurrence-free survival (3-yrRFS); secondary outcomes were correlation of pro-angiogenic factors with Ki-67 index, adverse pathologic factors, and CD31 expression, a marker of microvascular density. ResultsOf 144 GEP-NETs resected, STAT3 expression was high in 12 (8%) and low in 132 (92%) pts. High STAT3 expression was associated with worse 3-yrRFS compared to low expression (55% vs 84%; p = 0.003). High VEGF expression had a 3-yrRFS of 76% vs 82% for low expression (p = 0.09). HIF-1α expression was not associated with RFS. Ki-67 ≥ 3% was associated with worse 3-yrRFS (≥ 3%: 51% vs < 3%: 84%; p < 0.001), as was the presence of increased microvascular density (CD31 > median: 75% vs CD31 < median: 86%; p = 0.04). High STAT3 expressing tumors were more likely to have a Ki-67 ≥ 3% (42% vs 7%; p < 0.001). LVI was present in 82% of high STAT3 tumors compared to only 50% with low STAT3 (p = 0.058). CD31 expression was similar between groups (58% vs 49%; p = 0.5). ConclusionsIn resected GEP-NETs, high STAT3 expression is associated with an increased Ki-67 index, presence of lymphovascular invasion and worse 3-yr RFS. STAT3 may be a novel therapeutic target for patients undergoing resection of high-risk tumors.

Outcomes of post-operative treatment with concurrent systemic therapy and radiotherapy (RT) in intermediate (INT) risk resected oral cavity squamous cell carcinoma (OCSCC): A multi-institutional collaboration.

e17567 Background: Patients (pts) with adverse pathologic factors in resected OCSCC excluding positive surgical margins or extranodal extension represent a group of INT risk disease. Though not standard of care, adjuvant CRT is often used in INT pts. We conducted a multi-institutional study to evaluate factors associated with improved outcomes in INT pts treated with or without chemotherapy. Methods: An IRB-approved collaborative database of patients with primary OCSCC (Stage I-IVB AJCC 7th edition) treated with primary surgical resection between 1/1/2005 and 1/1/2015 with or without adjuvant therapy was established from 6 academic institutions. Pts were categorized by pathologic features and adjuvant therapy. Kaplan Meier curves, log-rank p-values and multivariate analysis (MVA) were used to describe outcomes by treatment including locoregional control (LRC) and disease free survival (DFS). Results: From a total sample size of 1270 patients, 455 INT risk pts were treated with primary surgical resection and adjuvant therapy; 95 received CRT, 274 received RT alone, and 86 received RT without recorded chemotherapy. 49% of pts had perineural invasion (PNI), 24.8% lymphovascular space invasion, 21.5% poorly differentiated histology, 47.3% with pT3/4 disease, and 27.9% with &gt; 2 lymph node positive (LN+). 55.8% of CRT pts were treated with cisplatin. &gt; 2 LN+ was the only significant predictor of LRC (HR 1.49, p= 0.049). PNI and &gt; 2 LN+ were significant predictors of DFS (HR 1.52, p= 0.003 and HR 1.76, p&lt; 0.001). On MVA, after adjusting for &gt; 2 LN+, treatment with cisplatin-RT was borderline significant for LRC (HR 0.52, p= 0.08). 3 year LRC in pts with &gt; 2 LN+ was 84.4% in pts treated with cisplatin-RT compared with 64.9% for RT alone. Conclusions: The addition of cisplatin-based CRT to INT risk pts is controversial but among pts with &gt; 2 LN+ there was a trend toward benefit. This study is limited by small numbers of pts treated with CRT, though these results highlight the need for further investigation in this population to identify INT pts who would benefit from adjuvant therapy intensification.

Association of Perioperative Transfusion with Recurrence and Survival After Resection of Distal Cholangiocarcinoma: A 10-Institution Study from the US Extrahepatic Biliary Malignancy Consortium.

Perioperative allogeneic blood transfusion is associated with poor oncologic outcomes in multiple malignancies. The effect of blood transfusion on recurrence and survival in distal cholangiocarcinoma (DCC) is not known. All patients with DCC who underwent curative-intent pancreaticoduodenectomy at 10 institutions from 2000 to 2015 were included. Primary outcomes were recurrence-free (RFS) and overall survival (OS). Among 314 patients with DCC, 191 (61%) underwent curative-intent pancreaticoduodenectomy. Fifty-three patients (28%) received perioperative blood transfusions, with a median of 2 units. There were no differences in baseline demographics or operative data between transfusion and no-transfusion groups. Compared with no-transfusion, patients who received a transfusion were more likely to have (+) margins (28 vs 14%; p = 0.034) and major complications (46 vs 16%; p < 0.001). Transfusion was associated with worse median RFS (19 vs 32months; p = 0.006) and OS (15 vs 29months; p = 0.003), which persisted on multivariable (MV) analysis for both RFS [hazard ratio (HR) 1.8; 95% confidence interval (CI) 1.1-3.0; p = 0.031] and OS (HR 1.9; 95% CI 1.1-3.3; p = 0.018), after controlling for portal vein resection, estimated blood loss (EBL), grade, lymphovascular invasion (LVI), and major complications. Similarly, transfusion of ≥ 2 pRBCs was associated with lower RFS (17 vs 32months; p < 0.001) and OS (14 vs 29months; p < 0.001), which again persisted on MV analysis for both RFS (HR 2.6; 95% CI 1.4-4.5; p = 0.001) and OS (HR 4.0; 95% CI 2.2-7.5; p < 0.001). The RFS and OS of patients transfused 1 unit was comparable to patients who were not transfused. Perioperative blood transfusion is associated with decreased RFS and OS after resection for distal cholangiocarcinoma, after accounting for known adverse pathologic factors. Volume of transfusion seems to exert an independent effect, as 1 unit was not associated with the same adverse effects as ≥ 2 units.