bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graded prognostic assessment index for renal cell carcinoma with brain metastases.
Authors: Garje Rohan , Dahiya Saurabh , Alva Venur Vyshak , Du Lingling , Osei-Boateng Kwabena , Elson Paul , Suh John H. , Chao Samuel T. , Ahluwalia Manmeet Singh 
Published: March 2020

e15537 Background: The GPA is a commonly used prognostic index based on RTOG protocols in patients with brain metastases (BM). The purpose of this study was to evaluate the utility of GPA index in a contemporary cohort of renal cell carcinoma with brain metastases (RCCBM) at a larger tertiary care center to predict overall survival. Methods: IRB approval was obtained and the Cleveland Clinic Brain Tumor and Neuro-Oncology Center’s database was used to identify RCCBM patients (pts) treated in the recent era (2000-12). A proportional hazards model was used to assess OS, which was measured from the date of diagnosis of brain metastases to death or last follow-up. Results: 136 RCCBM (100 males), median age 60 years (range 32-79), were evaluated. Pts had a median of 2 (range 1-15) BM; Karnofsky Performance Scale (KPS) was 90-100 in 57%, 70-80 in 38% and <70 in 5%. Extracranial metastasis was present in 93% of pts. OS was 15.0 months (95% C.I. 10.9-17.5). GPA for RCC consists of KPS (90-100, 70-80, <70) and the number of BM present (1, 2-3, >3).GPA was not prognostic for survival (p=.40), and neither GPA coding of KPS nor BM (1, 2-3, >3) was associated with outcome (p=.90 and .26, respectively). In contrast, diagnosis of RCC to BM >5 years, p=.004, brain as an initial site of metastasis, p=.005, normal hemoglobin, p=.01, a single BM, p=.02, controlled primary, p=.02, and age≤65 were found to be independently prognostic for improved OS. Using these factors, an alternative index can be formed. Conclusions: RCCBM specific GPA was notprognostic for OS in this study (p=.40), however a new index was developed based on a revised set of independent prognostic factors that was significant (p<.0001). [Table: see text]
Treatment decision and outcome in mRCC patients with different ECOG performance status.
Authors: Harmenberg Ulrika , Stenmo Kajsa , De Flon Caroline , Wersäll Peter , Sandström Per 
Published: March 2020

e15553 Background: Phase III studies with targeted agents have shown improved survival for mRCC. There is limited outcome data for the whole mRCC patient group. We collect data in a clinical registry at Karolinska for all patients with mRCC in the Greater Stockholm Region since 2007. Here we present the relationship between ECOG performance status and treatment outcome in this population. Methods: Between 2007 and 2012, 273 patients with mRCC were included in the registry. Patients were divided in two groups: Those that were treated with targeted agents and non- treated patients (symptomatically treated). Results: ECOG PS, available for 63%, was lower for patients treated (n=127) compared to patients not treated with systemic therapy (n=46) (median 1 vs. 2. Median OS from diagnosis to death in respective group was 731 day (n=106) and 269 days (n=55). The median OS from date of first metastasis to death was 500 days and 176 days respectively. In the treated group median OS from start of systemic therapy to death was 321 days. There was a difference in median OS from start of systemic therapy to death between patients who received 1 (n=52)(A), 2 (n=32)(B), 3 (n=16)(C) or > 3 lines (n=6)(D) with a median OS of 160.5 days, 395 days, 641 days and 728.5 days respectively. Mean PS at first line treatment was 1.36 for patients who received only one line and ≤ 1 for patients who received several lines. 13/18 patients with ECOG PS 0 at 1st line received >1 line, corresponding numbers for PS 1, 2 and 3 at 1stline were 21/40, 3/14 and 0/4. The average/ medians ECOG PS at time for the last treatment line were 1.36/1 (A), 1.47/1 (B), 1.64/2 (C) and 1.67/2 (D). Median OS from start of systemic treatment to death was dependent on PS at the start of treatment, ECOG 0 (n=18) 622 days, 1 (n=40) 724 days, ECOG2 (n=14) 226 days, ECOG3 (n=4) 44 days. Irrespective of treatment line, patients with PS 0-1 at initiation of any line of therapy had a 55% chance (47/86) of receiving a subsequent line of treatment, while patients with PS 2-3 only had a 19% chance (7/37). Conclusions: Patients with a good performance status, ECOG 0-1 at treatment start, had longer OS and received more lines of treatment. Patients with ECOG PS 3 could in our hands not be treated at all with targeted agents.
Final results from a trial of a combination herbal supplement for biochemically recurrent prostate cancer.
Authors: Dorff Tanya B , Tsao-Wei Denice D , Hawes Debra , Xiong Shigang , Quinn David I. , Gross Mitchell E. , Lieskovsky Gary , Vogelzang Nicholas J. , Groshen Susan G. , Pinski Jacek K. 
Published: March 2020

e16020 Background: No standard exists for the treatment of bcrPC. Concern over deleterious effects of androgen deprivation (ADT) and lack of proven survival benefit in this setting makes initiation of ADT inappropriate for some patients. A non-hormonal, non-toxic agent to reduce PSA would be a welcome alternative to observation. We tested Prostate Health Cocktail (PHC), a supplement containing vitamin D & E, saw palmetto, lycopene, green tea and soy extracts, in this population, to see whether it could decrease PSA. Methods: Eligible men had a rising PSA with doubling time between 3 and 36 months, with no evidence of metastases on CT and bone scan. After IRB approval, 40 men were treated with PHC 3 capsules PO daily for 4 week cycles. PSA was repeated after cycle 1, then every 2 cycles thereafter with imaging only as clinically indicated; the primary endpoint was PSA decline. PSA progression was defined as 25% increase above baseline/nadir AND absolute increase of 5 ng/mL or return to baseline. Circulating tumor cells (CTCs) were measured at baseline and after 3 cycles using parylene membrane filters. Results: 60 men screened, 17 failed (28%). Median age was 67 (range 54-84) and baseline PSA 2.8 ng/mL (1.1-84.1). 23% had primary radiation only, 25% had prostatectomy, and 52% had both; 23% had Gleason 8-10. The median # of cycles was 8 (1-13). 15/40 men (37.5%) had a PSA decline (1.1%-55% maximum decrease). 43% stopped therapy for PSA progression, with median time to progression 10.2 months. Circulating tumor cells were detected in 5 of the first 23 subjects; complete CTC data will be presented. There was no significant change in testosterone or DHT during treatment. Toxicities possibly related to PHC included grade 1 or 2 liver enzyme elevations [transient], grade 1 or 2 gastrointestinal symptoms (9), grade 1 weakness/dizziness/pain (5), and grade 1 fatigue (2). 5 men continue on study, 3 lost to f/u, 16 have developed metastases, median time to mets 31.5 months from bcr. Conclusions: PHC induced PSA declines in 37% of patients with bcrPC, and was not associated with changes in serum androgens or significant toxicities. PHC is a potential alternative to observation in select patients with bcrPC. Clinical trial information: NCT00669656.
Critical evaluation of MRI-targeted TRUS-guided transperineal fusion biopsy for detection of prostate cancer.
Authors: Kuru Timur H. , Roethke Matthias , Simpfendoerfer Tobias , Boxler Silvan , Seidenader Jonas , Schlemmer Heinz-Peter , Hohenfellner Markus , Hadaschik Boris 
Published: March 2020

e16063 Background: Precise staging of prostate cancer (PC) is essential for individualized treatment decisions. However, the majority of transrectal biopsies are negative for prostate cancer or show imprecise results. Additionally, the rate of upgrading in Gleason scores between biopsy and prostatectomy specimen is around 30-40%. MRI/TRUS fusion has shown encouraging results for detecting clinically significant prostate cancer. Methods: 412 consecutive patients with suspicion of PC were prospectively included in our database. The median age of patients was 65 years (range 42-84). Mean PSA level was 9.56 ng/ml (± 7.9ng/ml, SD). 55% of men had previous TRUS-guided biopsies, 45% underwent primary biopsy. Imaging data and biopsy results were analyzed and a self-designed questionnaire was send to all men regarding further clinical history and adverse effects of the biopsy. Results: In 236 of 412 (57.3%) biopsy samples showed PC. 71.6% of biopsy proven PC were clinically significant (D’Amico criteria). On multiparametric (mp)-MRI, 120 men were reported as highly suspicious for PC and in these tumor detection rate was 83.3% (100/120). In patients without cancer-suspicious MRI-lesions, 31,8% (42/132) men were diagnosed with significant disease (Table 1). Regarding adverse effects, 152 patients (49%) reported hematuria after biopsy. 9 patients (2%) needed temporary catheterization after biopsy due to prostate swelling. In three patients (0.7%) febrile urinary tract infection occurred after biopsy. Major limitation is the limited follow-up of 12-months of biopsy-negative patients. Conclusions: MRI-targeted TRUS-guided transperineal fusion biopsy provides high detection rates of clinically significant tumors. mp-MRI still has its limitations, and therefore systematic biopsies should currently not be omitted. The morbidity of the transperineal saturation approach is reasonable and mainly self-limiting. [Table: see text]
Phase I study of cisplatin (cDDP)/hyperthermia (HT)/lapatinib (Lap) in patients (pts) with recurrent carcinoma of the uterine cervix (rCC) in previously irradiated area (PIA).
Authors: Meerten Esther Van , Westermann A.M. , van Doorn H. C. , Franckena Martine , Kraan Jaco , Wiemer Erik A.C. , Sleijfer Stefan 
Published: March 2020

e16504 Background: Pts with rCC in PIA might benefit from cDDP plus HT. Lap inhibits the intracellular tyrosine kinase domain of the epidermal growth factor receptor (EGFR) and HER2. Overexpression of EGFR and HER2 is often seen in pts with CC and might be involved in chemotherapy resistance. Besides, preclinical data suggest a synergistic effect of combining cDDP and Lap. Therefore, this phase I dose-escalation study was performed to determine the maximum tolerated dose (MTD) of Lap added to fixed doses of cDDP and HT. Methods: Pts with rCC in PIA, adequate organ function and ECOG performance status 0-1 were scheduled for 6 weekly administrations of 70 mg/m2cDDP plus locoregional HT. Daily Lap was added on days 1-56, starting at a dose-level of 1000 mg. The MTD was defined as the highest dose where ≤1/6 pts experienced dose-limiting toxicity (DLT). Safety, pharmacodynamics (PhD) and response were assessed. Results: Eight pts were treated. The first 4 pts (2 each at dose 1000 mg and 750 mg) experienced DLT. Of the 4 pts treated at dose level -2 (500 mg), only 1 pt was able to complete the treatment as planned, 2 pts experienced a DLT and 1 pt was not evaluable (NE), because of early progressive disease (PD) (see Table). In the evaluable pts 1 PD, 4 stable diseases and 2 partial responses (PR) were observed. One patient with PR had a resection of the local recurrence. Analysis of the resected specimen showed a pathological complete response (pCR). Enumeration of circulating endothelial cells measured at baseline and during therapy did not show consistent results. The same applied for the PhD on Ki-67, p27Kip1and EGFR in pretreatment and on-therapy skin biopsies. Conclusions: It is not feasible to combine Lap with fixed doses of cDDP and HT in pts with rCC in PIA mainly due to increased cDDP-related toxicity. The observed pCR is intriguing and warrants further investigation of combining HER2-blockade and cDDP/HT. Clinical trial information: NL24464.078.08. [Table: see text]
Expression of mEGFR, pEGFRThr654, and pPKN1Thr774 to predict response to chemoradiation and prognosis in patients with cervical cancer.
Authors: Lang Jin Yi , Huang Jianming , Lai Xin 
Published: March 2020

e16531 Background: The aim of this study was to determine the relation between proteins involved in phosphorylation of EGFRThr654 and response to chemoradiation and survival in a well-documented series of cervical cancer patients. Methods: Pre-treatment tissue samples of 90 consecutive FIGO stage IIA-IIIB cervical cancer patients treated with concurrent chemoradiotherapy between January 2007 and December 2009 were collected. Clinicopathologic and follow-up data were collected by a retrospective chart review. Protein expression of membranous EGFR (mEGFR), pEGFRThr654 and pPKN1Thr774 were examined by immunohistochemistry on FFPE tumor specimens. The correlations between protein expression and clinicopathological factors and outcomes were analyzed. Results: mEGFR staining was present in 67.78%, pEGFRThr654 in 91.11%, pPKN1Thr774 in 56.67% of tumors. pEGFRThr654 staining was positively correlated to pPKN1Thr774 (p = 0.04) and to mEGFR staining (p = 0.015). In multivariate analysis, nuclear staining of pEGFRThr654 [hazard ratio(HR)= 4.833; 95%CI=1.959-11.922, P=0.001)] and cytoplasmic staining of pPKN1Thr774 (HR=3.095; 95%CI=1.019-9.406; P=0.046) were prognostic factors for poor overall survival (OS) and also were independent predictors of poor response to (chemo)radiation for progress-free survival (PFS) (HR=2.921, 95%CI=1.360-6.274, P=0.006; HR=2.963, 95% CI=1.187-7.394, P=0.020), and mEGFR staining was an independent prognostic factor for poor PFS (HR=5.934, 95% CI=1.378-25.555, p=0.017). The high expression of pEGFRthr654 is related to poor local control rate (p = 0.000) and to poor short-term efficacy (p = 0.009). Conclusions: mEGFR and pEGFRThr654 immunostaining are frequently observed and independently associated with poor response to therapy and poor PFS and OS in cervical cancer patients primarily treated by concurrent chemoradiotherapy. Our data presents the pEGFRThr654 nuclear translocation as a promising target in Integrated therapies of chemoradiotherapy combined with targeting inhibition of pEGFRThr654 and its nuclear import for cervical cancer.
Oral cavity squamous cell carcinoma in the elderly: A retrospective study in 129 patients over 11 years (2000-2010).
Authors: Gambotti Laetitia , Schwob Emilie , Goudot Patrick , Bertolus Chloë 
Published: March 2020

e17023 Background: There is no consensus for the management of elderly patients with oral cavity squamous cell carcinomas (OC SCC). Surgeons have to estimate for each patient the benefit or the risk of aggressive treatments in this population. We report the experience of one French university hospital center in the treatment of OC SCC in patients aged > = 70 years. Methods: One hundred and twenty nine patients aged > = 70 years with a primary OC SCC diagnosed between 2000 and 2010 were included retrospectively. Independent risk factors of post-operative complication were identified using a logistic regression. Overall survival (OS) was estimated with Kaplan Meier method. Independent factors of survival were calculated using a Cox model. Results: Mean age was 78 (+/-6), sex ratio was 1.2. Women presented significantly more precancerous lesions (36% vs 21%, p=0.04), less alcohol intoxication (13% vs 59%, p<0.001) and less tobacco consumption (41% vs 81%, p<0.001). Half of the sample was stage T4 of TNM classification. Eighty eight percent of the patients received a curative treatment, including surgery for 101 patients. Among them, the surgical treatment was considered as “standard” (vs “substandard”) for 70%. Thirty percent of the surgical patients presented a post-operative complication. Independent risk factors of complications were T3/T4 stage (OR 4.5 [1.3-15.1]) N+ (vs N0 of TNM classification) (OR 7.3 [2.2-24.0]) and alcohol intoxication (OR 3.6 [1.1-11.4]). The median OS was 13.6 months (43.8 months for T1). There was no significant difference of OS between standard or substandard treatment groups. The independent negative prognostic factors for OS were age > 79 years (HR 1.8 [1.2-2.7]), N+ (HR 1.9 [1.3-2.9]) and ASA score 3/4 (HR 1.8 [1.1-2.9]). Conclusions: In our experience, surgeons probably made the good choice between standard or substandard treatment according to the patient profile but this choice must be oriented by professional guidelines.
Patterns of resource utilization and cost for postmenopausal women with hormone-receptor–positive (HR+), HER2-negative (HER2–) advanced breast cancer (ABC) in Europe.
Authors: Jerusalem Guy Heinrich Maria , Neven Patrick , Marinsek Nina , Zhang Jie , Degun Ravi , Benelli Giancarlo , Saletan Stephen , Andre Fabrice 
Published: March 2020

e17520 Background: Healthcare resource utilization varies by disease stage and treatment choice. Notably, chemotherapy (CT) use is associated with extensive healthcare resource utilization and cost. This study reviews the direct and indirect cost implications of CT versus hormonal therapy (HT) in the ABC setting through the first 3 lines of treatment. Methods: A retrospective chart review of postmenopausal women diagnosed with HR+, HER2– ABC in 5 European countries was conducted. Patients must have progressed on at least 1 line of HT and completed at least 1 line of CT in the ABC setting. Patient cohorts based on therapy received in each line were constructed (cohort A: HT 1st-line, CT 2nd-line, and any treatment 3rd-line; cohort B: HT 1st- and 2nd-line with CT 3rd-line; and cohort C: CT 1st-line with any 2nd- and 3rd-line). Costs of care based on resource utilization and country-specific cost were calculated by patient cohort and line of therapy. Working status was also assessed. Results: A total of 355 eligible patient charts between 2008 and 2012 were included in the analysis: cohort A, 218 (61%) patients; cohort B, 26 (7%) patients; and cohort C 111 (31%) patients. Total direct costs over all 3 treatment lines were €14,362 higher for CT versus HT as 1st-line therapy (cohort C vs A) and €10,368 higher for CT versus HT as 2nd-line (cohort A vs B). Monthly direct costs were €2,536 higher for CT versus HT for 1st-line therapy and €1,713 higher for CT versus HT in 2nd-line. Increased costs for CT were due to treatments to manage side effects, use of concomitant targeted therapies, and increased frequency of hospitalizations, healthcare provider visits, and monitoring tests. On switching from HT to CT, there was a doubling of the proportion of patients on sick leaves in both cohorts A and B. Conclusions: These results suggest an increased direct cost of care for CT relative to HT in European postmenopausal women with HR+, HER2– ABC. Furthermore, CT-based therapy appears to be associated with lower productivity of working-age patients, potentially increasing overall indirect costs.
Cancer anorexia-cachexia syndrome in advanced lung cancer: An exploratory analysis of patient-reported outcomes data.
Authors: Nipp Ryan David , Locke Susan C. , Samsa Gregory , Kamal Arif , Abernethy Amy Pickar , LeBlanc Thomas William 
Published: March 2020

e17521 Background: The cancer anorexia-cachexia syndrome (CACS) is a debilitating syndrome of involuntary weight loss, anorexia, declining function, muscle catabolism, and inflammation. It affects many patients with cancer, especially those with advanced disease. We aimed to describe the experience of a group of patients with advanced lung cancer who meet published weight-based criteria for CACS. Methods: Tablet computers were used to collect patient-reported outcomes data from 97 patients with advanced non-small cell lung cancer, using the Patient Care Monitor v2.0 and the FACIT family of questionnaires. 25 patients met published weight criteria for CACS (>=5% weight loss in the past 6 months). 51 patients with stable weights were used as a comparison group; those lacking weight data were excluded. Statistical comparisons were made between these groups to explore differences in symptoms, quality of life, and survival. Results: Patients meeting weight criteria for CACS had lower serum albumins (median 3.7 vs. 3.9, p=0.006) and worse performance status by Karnofsky and ECOG (70 vs. 80, p=0.004, and 2 vs. 1, p=0.027). CACS patients had worse FAACT anorexia-cachexia subscale scores (34.5 vs. 38.5, p=0.018) but were not statistically more likely to be prescribed CACS therapies; only 17% of patients in the CACS group were on medication for this (N=4). FACIT fatigue subscale scores were not statistically different between groups, nor was quality of life by FACT-G. Grip strength and 6-minute walk distance were also not statistically different. Patients in the CACS group had a significantly shorter survival (HR 2.066 [95% CI=1.229,3.474], p=0.005). Conclusions: Patients with advanced non-small cell lung cancer who meet standard weight-based criteria for CACS have inferior survival compared to a similar population without weight loss. Though traditional descriptions of CACS presume a general impairment in quality of life, we did not find statistical differences here aside from the anorexia-cachexia subscale score of FAACT. Few patients were prescribed medication to address symptomatic anorexia/cachexia, suggesting it may be an unmet need in patients with advanced lung cancer.
Should adjuvant zoledronic acid be used in early-stage, endocrine-sensitive breast cancer?
Authors: Lamond Nathan William Dana , Skedgel Chris , Rayson Daniel , Younis Tallal 
Published: March 2020

e17564 Background: Adjuvant zoledronic acid (ZA) appears to improve disease-free survival (DFS) in women with endocrine-sensitive breast cancer and low estrogen levels (LEL) including post-menopausal women, and pre-menopausal women treated with LHRH agonists. ZA, however, is also associated with potential adverse events and incremental drug acquisition costs. An overall assessment of the long-term clinical and economic impacts of adjuvant ZA may therefore help guide the decision to adopt this novel therapeutic option. We examined the incremental quality-adjusted life-years (QALY) and costs per QALY associated with adjuvant endocrine treatment plus ZA relative to endocrine treatment without ZA in women with endocrine-sensitive breast cancer and LEL. Methods: A generic state-transition model was developed to compute cumulative costs, from a Canadian perspective, and QALY associated with and without adjuvant ZA (4 mg IV qM*3→ q3M*8 → q6M*5) over a 25-year horizon for women with endocrine-sensitive breast cancer and LEL. Costs, utilities, DFS and adverse events were derived from relevant clinical trials, the literature and local resources. One-way and probabilistic sensitivity analyses were conducted for key model parameters. Results: Adjuvant ZA was associated with incremental QALY gains of 0.80 and 0.52 and resultant CU estimates of $3,571 and $7,683 per QALY gained in pre- and post-menopausal women, respectively. CU estimates were robust across reasonable uncertainty ranges in all parameters. Conclusions: Adjuvant ZA appears to be associated with long-term QALY gains in women with endocrine-sensitive breast cancer and LEL as well as CU estimates that are well below commonly accepted North American thresholds. The favourable long-term clinical and economic impacts observed in this study further support the use of adjuvant ZA in this setting.