bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and external validation of a novel risk score to identify insignificant prostate cancer.
Authors: Dutto Lorenzo , Witt Jorn H. , Urbanova Katarina , Wagner Christian , Schuette Andreas , Addali Mustafa , Kelly John D , Nathan Senthil , Briggs Timothy Philip , Sridhar Ashwin , Gori Stefania , Ahmad Amar , Shaw Gregory 
Published: September 2018

5073 Background: Active surveillance is increasingly used for insignificant prostate cancer (PCa). In order to identify suitable patients, risk scores have been developed which use pre-operative factors. We evaluated the accuracy of 9 separate tools developed to identify patients harbouring insignificant PCa in 2613 patients who underwent radical prostatectomy for Gleason 3+3 PCa. We have developed and validated a novel risk score to correctly identify insignificant PCa for use in unscreened patient cohorts using non-dichotomised clinical predictors. Methods: 2799 patients who would have been candidates for AS (Gleason score 6 only) patients underwent robotic radical prostatectomy between 2006 and 2016 at a tertiary referral center. The volume and grade of tumour in the resected prostate was analysed. Inignificant PCa was defined as Gleason 3+3 only, index tumour volume <1.3 cm3 , total tumour volume <2.5 cm3 (updated ERSPC definition). 2613 patients were included in the final analysis. We computed the accuracy (specificity, sensitivity and area under the curve (AUC) of the receiver operator characteristic) of 9 predictive tools. Multivariate logistic regression with elastic net regularisation was used to develop a novel tool to predict insignificant prostate cancer using age at diagnosis, baseline PSA, TRUS volume, clinical T-stage, number of positive cores and percentage of positive cores as predictors. This tool was validated in an external cohort of 441 unscreened patients undergoing surgery for Gleason 6 PCa. Results: All of the predefined tools rated poorly as predictors of insignificant disease as none of them reached the required AUC threshold of 0.7. The new tool performed well in training and validation cohorts. Conclusions: Pre-existing predictive tools to identify indolent PCa have a poor predictive value when applied to an unscreened cohort of patients. Our novel tool shows good predictive power for insignificant PCa in this population in training and validation cohorts. The inherent selection bias due to analysis of a surgical cohort is acknowledged. [Table: see text]
Association of risk of clinical recurrence (CR) and prostate cancer death (PCD) with a 17-gene genomic prostate score (GPS) value <20.
Authors: Febbo Phillip G. , Crager Michael , Burke Emily , Lawrence H. Jeffrey , Cullen Jennifer , Klein Eric A. 
Published: September 2018

5074 Background: Over-treatment of localized prostate cancer (PC) can result from over-estimation of a patient’s risk of CR and PCD. GPS (scale 0-100) has been validated to predict adverse pathology, biochemical recurrence, metastasis, and PCD and provides a more accurate overall assessment of patient risk than clinical risk factors alone. A recent validation study found that no patients with AUA Low- or Intermediate-risk disease and a GPS of <20 developed PC metastases or PCD. Here, 2 large longitudinal PC cohorts were analyzed to estimate the risk of CR and PCD for GPS <or >20 units. Methods: Data from Klein et al. European Urology (EU) 2014 and Cullen et al. EU 2014 were analyzed to establish the risk of CR and PCD associated with a pre-established GPS cut-point of 20. Patients were divided based on the value of GPS (≤20, >20). Cox regression analyses accounted for cohort sampling weights. Since GPS was developed using Klein et al, standardized hazard ratios (std HR, HR for 1 SD change in the covariate) for GPS and CR and PCD survival curves for the 2 groups were estimated correcting for regression to the mean (RM). Results: Of the 402 patients in Cullen et al. (median follow up 5.2 years), only 5 patients developed metastases; all 5 had GPS >20. For Klein et al., of 426 patients with a median follow up of 6.6 years, there were 109 CR (metastasis and local recurrence) and 39 PCD; only one patient with events had a GPS <20. Overall 28% of patients had GPS <20. GPS was a significant predictor for both CR (std HR 2.50 (95%CI 1.99, 3.15, p <0.001, RM-corrected std HR 2.16, FDR <0.1%) and PCD (std HR 2.90 (95% CI 2.06,4.06, p<0.001, RM-corrected std HR 1.96, FDR <0.1%) after adjustment for AUA group. Men with intermediate risk prostate cancer and a GPS score of < 20 have a 2.6% and 0.7% 10-year RM-corrected risk of CR and PCD, respectively (Table 1). Conclusions: GPS strongly predicts risk of CR and PCD in men with AUA Low- or Intermediate-risk PC. Patients with a GPS score <20 have a very low risk of CR or PCD and should be considered for AS. [Table: see text]
Long-term results of a prospective phase II study of androgen deprivation therapy, external radiation, cs-131 brachytherapy, and adjuvant docetaxel in high-risk prostate cancer.
Authors: Rice Stephanie , Le Gloribel K , Hussain Arif , Mannuel Heather Dorothy , Naslund Michael K , Amin Pradip P. , Kwok Young 
Published: September 2018

5079 Background: We report the long-term results of a prospective, Phase II study of 2 years androgen deprivation therapy (ADT), 45 Gy bone marrow sparing pelvic radiation (BMS-PR), Cs-131 brachytherapy boost (85 Gy), and 4 cycles of adjuvant docetaxel (75 mg/m2 q21d + prednisone) in high risk, localized prostate cancer. Methods: From2006-2014,38 patients were enrolled. Acute hematologic as well as acute and chronic gastrointestinal (GI) and genitourinary (GU) toxicities were scored based on the CTCAE v3.0 criteria. Biochemical recurrence was defined as a nadir + 2 rise in PSA. Actuarial freedom from PSA failure (bNED) and overall survival (OS) were calculated using SPSS v24. Median Gleason score was 8 (74% Gleason 8-10). Median PSA was 11.2 (range 2.8-96). Results: A total of 38 patients were enrolled on the trial. Median age was 62 years (range 45-82). 82% of patients completed all protocol specified treatments, while 84% completed all 4 cycles of docetaxel. After a median follow up of 44 mo (range 3.4-118), the 5-year bNED rate was 86% while 5-year OS was 80%. Acute grade ≥ 2 GI and GU toxicity rates were 12.5% and 21.9%, respectively. Chronic grade ≥ 2 GI and GU toxicity rates were 3.1% and 3.1%, respectively. 25.6% (n = 10) patients receiving docetaxel developed grade 4 hematologic toxicity. There were no grade 5 toxicities. Conclusions: We found this aggressive multi-modal approach to be feasible, safe, well-tolerated, and effective. It does not appear that BMS-PR decreases hematologic toxicity. Cs-131, with its 9.7 day half-life, does not appear to increase acute or late toxicity. These data build upon the ASCENDE-RT and RTOG 0521 trials that demonstrate the added benefits of brachytherapy boost and adjuvant docetaxel, respectively, in high-risk prostate cancer.
Mastectomy rates in relation to adoption of a margin guideline.
Authors: Morrow Monica , Katz Steven J. , Jagsi Reshma 
Published: September 2018

508 Background: Surgery after initial lumpectomy to obtain a bigger negative margin is common and may lead to mastectomy. The impact of a 2014 consensus statement endorsing a minimal negative margin for invasive breast cancer on surgeon attitudes, re-excision rates, and final surgical procedure is uncertain. Methods: Women with stage I and II breast cancer diagnosed between 7/13–8/15 and reported to the Los Angeles and Detroit SEER registries were surveyed about 2 months post diagnosis, and 70% responded; 3729 comprise the analytic sample. All attending surgeons identified by the patients (n=489) were sent a questionnaire at the end of the patient survey period, and 376 (77%) responded. Pathology reports were reviewed for margin status. Multinomial regression models were used to assess trends. Results: The 67% initial lumpectomy rate was unchanged during the study. The final lumpectomy rate increased by 13% (to 65% from 52%) from 2013–2015, accompanied by a decrease in unilateral (to 18% from 27%) and bilateral (to 16% from 21%) mastectomy (p=0.002). Surgery after lumpectomy, both re-excision and mastectomy, declined by 16% (p<0.001). Pathology review showed no association between date of treatment and positive margins. Patient report of surgeon-recommended mastectomy after initial lumpectomy declined to 8% from 20% (p<0.001). 69% of surgeons endorsed a margin of no ink on tumor to avoid re-excision in ER+PR+ cancer and 63% for ER-PR- cancer. Surgeons treating >50 breast cancers annually were more likely to accept this margin than those treating <20 cases (p<0.001). Conclusions: Additional surgery after initial lumpectomy markedly decreased between 2013‒2015 after publication of a margin guideline endorsinga minimal negative margin. This resulted in a substantial increase in lumpectomy as the definitive surgical procedure, which illustrates that guidelines can be an effective, low-cost approach to addressing clinical controversies.
Prostate cancer (PCa) in 696 hypogonadal men with and without long-term testosterone therapy (TTh): Results from a controlled registry study.
Authors: Haider Ahmad , Haider Karim Sultan 
Published: September 2018

5085 Background: There is no evidence that TTh in men with hypogonadism increases PCa incidence or severity. A Canadian group recently found that long-term TTh decreased the risk of PCa diagnosis (Wallis et al., Lancet Diab Endocrinol 2016; 4:498). We assessed incidence and severity of PCa in hypogonadal men on long-term TTh (T-group) in comparison to an untreated hypogonadal control group (CTRL). Methods: 400 men with testosterone ≤350 ng/dL and symptoms received testosterone undecanoate 1000 mg every 3 months for up to 10 years. 296 hypogonadal men (57-74) opted against TTh. Median follow-up: 8 years. Total observation time covered more than 5,000 patient-years. Prostate volume (PV), PSA, weight and C-reactive protein (CRP) were measured and digital rectal examination/transrectal ultrasound performed before treatment initiation and then every 6-12 months. Biopsies were performed when indicated according to EAU guidelines. Results: In the T-group, PV increased slightly but significantly by 2.41 mL (p < 0.0001), PSA by 0.22 (NS). In CTRL, PV decreased slightly but significantly by -1.20 mL (p < 0.005), PSA by -0.38 (p < 0.0001). Weight dropped by 18.23% in the T-group and increased by 1.78% in CTRL, CRP decreased significantly in the T-group and remained unchanged in CTRL. In the T-group, 9 men (2.3%) were diagnosed with PCa. In CTRL, 15 (5.1%) were diagnosed with PCa. The incidence per 10,000 years was 29 in the T-group and 102 in CTRL. The mean baseline age of PCa patients was 65 years in the T-group and 65.5 in CTRL. Prostatectomy was performed in all men. In the T-group, all but 1 patient had a Gleason score ≤6, and all a predominant Gleason score of 3. Tumor grade was G2 in all 9 (100%), tumor stage T2a in 7 (78%) and T2b in 2 (22%) patients. In CTRL, Gleason score was > 6 in all 15 patients. 4 men had a predominant Gleason score of 3, 10 had 4, and 1 had 5. Tumor grade was G2 in 7 (46.7%) and G3 in 8 (53.3%) patients, tumor stage T2b in 1 (6.7%), T2c in 1 (6.7%), T3a in 1 (6.7%), T3b in 7 (46.7%) and T3c in 6 (50%) patients. Conclusions: In hypogonadal men, TTh may decrease PCa incidence compared to CTRL. PCa was less severe in the T-group. Weight loss and reduced inflammation by TTh may have contributed to our findings.
COOLHAIR: A prospective randomized trial to investigate the efficacy and tolerability of scalp cooling in patients undergoing neoadjuvant chemotherapy for early breast cancer.
Authors: Smetanay Katharina , Junio Philippe , Feißt Manuel , Hassel Jessica Cecile , Mayer Luisa , Matthies Lina Maria , Schumann Arina , Hennigs André , Heil Joerg , Sohn Christof , Jaeger Dirk , Schneeweiss Andreas , Marme Frederik 
Published: September 2018

525 Background: Chemotherapy induced alopecia (CIA) is a distressing side effect for women with breast cancer (BC) undergoing chemotherapy (CT). Scalp cooling is a method aiming to prevent CIA, but its efficacy is not well defined. Observational studies show a positive effect of scalp cooling to reduce hair loss, but randomized trials until recently have been lacking. Methods: In our monocentric prospective randomized trial patients with early BC undergoing (neo)adjuvant CT were 1:1 randomized to either scalp cooling (CAP) or not (noCAP). All patients received 18 to 24 weeks of anthracycline (A) and/or taxane (T)-based CT. The DigniCap System was used for scalp cooling. The primary endpoint was patient reported rate of alopecia according to the Dean Scale (Grade 0: no hair loss, grade 1: > 0 - 25%; grade 2: > 25 - 50%; grade 3: > 50 - 75%; grade 4: > 75%). Hair preservation was defined as hair loss £ grade 2. Secondary endpoints were rate of alopecia determined by nursing staff and an independent and blinded evaluator, rate of wig/scarf use as well as quality of life. Results: From August 2014 until January 2016 seventy-nine patients were included (41 CAP and 38 noCAP). The drop-out rate was 32% in the CAP arm and 34% in the noCAP arm. Main reasons for drop out were hair loss, adverse events (CAP) and randomization into control arm. At the time of this analysis all patients had completed CT. Hair preservation was observed in 39% of patients in the CAP arm versus 0% in the No CAP arm (p < 0.001). There was a strong concordance between patients and staff evaluation (weighted Cohen's Kappa = 0.92). Wig/scarf use was significantly less frequent in the CAP group (36% vs 92% at home, p < 0.001; 64% vs 91% outside, p < 0.001). We did not observe any differences in hair preservation between A-based and non A-based regimens. Conclusions: Our prospective randomized trial shows that scalp cooling is effective in preventing CIA in a relevant number of patients. This option should be made available for patients undergoing T+/-A-based (neo)adjuvant chemotherapy for EBC.
Yoga in women undergoing treatment for breast cancer: Impact on quality of life in a randomized controlled trial.
Authors: Nair Nita S. , Goel Nishu Singh , Hawaldar Rohini W , Siddique Shabina , Parmar Vani , Pandey Aarti , Badwe Rajendra A. 
Published: September 2018

527 Background: Yoga has been tested in multiple small-randomized studies for its impact on quality of life (QOL) on breast cancer (BC). We propose to study the effect of yoga on disease free survival as the primary endpoint in women with operable breast cancer. (Study methodology details refer to NCT02161900). Methods: Women with non-metastatic BC were randomized to yoga and conventional exercise (YCE) versus conventional exercise only (CE) in addition to standard therapy. Over and above documentation of recurrence and death, QOL was assessed in these women using the EORTC QLQC30, BR23, Brief fatigue inventory (BFI), Visual pain scores (VPS) and a spirituality questionnaire (SQ). EORTC QLQ was assessed at baseline (BL), 6-9 months (mo), 18-21 mo. BFI and VPS at BL, 6-8 mo and 12-15 mo and SQ at BL and 12-15 mo. We report the first interim analysis of QOL in 605 patients randomized to the study with atleast 1 year of follow up. The groups were balanced in both arms with respect to clinico-pathological factors. Results: At 6-9 mo (completion of adjuvant therapy), there was no significant difference in global QOL scores (p = 0.08), however 52% women on YCE showed an improvement from baseline compared to 42% in CE. At 18-21 mo emotional function scores were better in YCE (p = 0.002); with lesser systemic side effects in YCE arm (44% vs 56% p = NS). The median score of fatigue after adjuvant therapy measured by QLQ C30 was lower in YCE (17.37vs22.22, p = 0.003) which was similar to that observed by BFI at 12-15 mo (1.6vs 2, p = 0.04). Also in YCE there was lower reporting of detriment in general activity (41%vs 59%) and mood (34%vs66%) (p = NS). In VPS at 12-15mo, the median scores for pain intensity (p = 0.042), pain on movement (p = 0.038), pain on mobilization (p = 0.008) were lower in YCE. Lastly SQ assessed spirituality and showed no difference, but less deterioration compared to baseline scores in YCE. Conclusions: Yoga did not show a significant difference in global QOL but had a major benefit reaching statistical significance in fatigue, emotional score and pain. Yoga is a low-risk, low-cost complementary therapy that may improve compliance to therapy by improving parameters that can affect day-to-day activity in women with breast cancer. Clinical trial information: NCT02161900.
Effects of age, immune landscape, and response to trastuzumab (H) in HER-2 positive (HER2+) breast cancer in NCCTG (Alliance)-N9831.
Authors: Soyano Aixa Elena , Serie Daniel , Mashadi-Hossein Afshin , Warren Sarah , Colon-Otero Gerardo , Knutson Keith L. , Perez Edith A. , Moreno-Aspitia Alvaro , Thompson E Aubrey , Chumsri Saranya 
Published: September 2018

530 Background: Therapeutic efficacy of H involves activation of the immune system.Age-dependent progressive deterioration of the immune response is referred as immunosenescence. In HER2+ breast cancer, the effects of aging and the ability of H to activate endogenous anti-tumor immunity is unknown. A previous report from HERA trial showed no significant increase in risk of early recurrence with age (≤ or > 40). We evaluated the long-term outcome of HER2+ patients (pt) related to age and immune landscape. Methods: 1,392 pt from N9831 trial were evaluated. Stromal tumor infiltrating lymphocytes (sTIL) were evaluated in H&E slides. Lymphocyte predominant breast cancer (LPBC) was defined as sTIL ≥ 50%. Molecular TIL (mTIL) and immune subset signatures were evaluated using NanoString research CodeSets. Cox proportional hazard ratio (HR) was used for analysis. Results: There were 1,111 (79.8%) pt > 40 years old (yo) and 281 (20.2%) pt ≤ 40 yo. Younger age was significantly associated with hormone receptor positivity (p 0.00011) and luminal B subtype (p 0.011). With a median follow up of 10.6 years, there was no significant difference in long-term outcome among pt ≤ 40 vs. > 40 yo who received H (HR = 0.88 (0.62-1.24), p = 0.45). Similar findings were observed when age was dichotomized at 50 and 60 yo. While there was no association between sTIL and age, a small but significant increase in mTIL CD45 expression with age (p 0.003) was observed. Similar small increases in cytotoxic cell (p 0.007) and T cell (p 0.015) immune scores were also observed with increasing age. Among pt who received chemotherapy alone, pt > 40 yo with LPBC (n 55) had excellent outcome with 92.4% recurrence free survival (RFS) at 10 years. However, there was no significant difference in RFS among pt ≤ 40 yo with or without LPBC. Conclusions: Among pt treated with H, there was no significant difference in outcome related to age. In contrast to a decline expected from immunosenescence, we observed small but significant increases in mTIL signatures for total lymphocytes, cytotoxic, and T cell subsets. Among patients who received chemotherapy alone, our data suggested that pt > 40 yo with LPBC had excellent prognosis, compared to pt > 40 yo without LPBC.
A population-based analysis of treatment and outcomes in 2,500 metaplastic breast cancer patients.
Authors: Ong Cecilia Tuongquang , Thomas Samantha Marie , Campbell Brittany Morgan , Greenup Rachel Adams , Plichta Jennifer Kay , Rosenberger Laura Horst , Force Jeremy Meyer , Hyslop Terry , Hwang Eun-Sil Shelley , Fayanju Oluwadamilola Motunrayo 
Published: September 2018

532 Background: Metaplastic breast cancer (MBC) is a rare, aggressive variant that is often triple negative (TN). Current guidelines recommend use of standard receptor-based treatment for MBC despite evidence of chemoresistance. We sought to compare treatment patterns and outcomes of MBC and non-MBC. Methods: Women age > 18 with stage I-III MBC and non-MBC histology diagnosed from 2010-2013 were identified in the National Cancer Database. Kaplan Meier and multivariate Cox proportional hazards models were used to estimate MBC association with overall survival (OS). Subgroup analyses were conducted for (1) MBC patients only and (2) TN MBC and TN non-MBC patients. Results: 2451 MBC and 568,057 non-MBC patients were included. 70.3% of MBC were TN vs 11.3% of non-MBC (p < 0.001). 19.2% of MBC were luminal (i.e., ER+ and/or PR+, and HER2-). MBC presented with higher clinical T stage (cT4: 5.4% vs 1.8%) and grade (grade 3: 72.1% vs 29.7%) but was less frequently node-positive (19.1% vs 29.7%, all p < 0.001). A higher proportion of MBC patients were treated with mastectomy (59.0% vs 44.9%), axillary dissection (ALND, 35.2% vs 32.2%), and chemotherapy (74.1% vs 43.1%, all p≤0.001). 5-year OS was reduced among MBC vs non-MBC patients for both the entire cohort (72.7% vs 87.5%) and the TN-only analysis (71.1% vs 77.8%, both log-rank p < 0.001). Among MBC cases, TN subtype was not associated with worse OS than the luminal subtype (HR 1.16, p = 0.28). Chemotherapy (HR 0.69, p = 0.004) and/or radiotherapy (HR 0.52, p < 0.001) improved OS in MBC, and the proportional benefit of chemotherapy did not vary with pathological T or N stage (interaction p > 0.05 for both). Among TN patients, a higher proportion of TN MBC patients underwent mastectomy (58.4% vs 49.5%, p < 0.001), but in contrast to the full cohort, a lower proportion of TN MBC patients received chemotherapy (76.6% vs. 78.7%, p = 0.008) and ALND (35.2% vs. 38.2%, p = 0.01) vs TN non-MBC patients. Conclusions: MBC had worse OS vs non-MBC, and unlike other histologies, outcome was not driven by receptor status. Multimodal therapy improved outcomes. Further investigation into MBC tumor biology and the development of MBC-specific guidelines could potentially improve treatment standardization and outcomes.