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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e16126-e16126
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. 4579-4579
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 5_suppl ( 2012-02-10), p. 399-399
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 5_suppl ( 2012-02-10), p. 399-399
    Abstract: 399 Background: Recently, the R.E.N.A.L. nephrometry scoring system was introduced to objectively describe renal masses with respect to size, the degree to which they are exo/endophytic, the nearness to the collecting system, whether they are anterior or posterior and the location relative to polar lines. It is our aim to evaluate the R.E.N.A.L. nephrometry scoring system’s ability to predict functional renal loss attributed to nephron-sparing surgery (NSS). Methods: We evaluated 42 patients presenting with either an anatomic (32) or functionally solitary (10) kidneys undergoing partial nephrectomy (PN). Each renal unit was assigned a R.E.N.A.L. nephrometry score utilizing pre-operative cross-sectional imaging. The CKD−EPI equation was applied to serum creatinine levels to generate corresponding estimated glomerular filtration rates (eGFR). The difference between the eGFR at baseline and at post-operative time points served as a measurement of renal function loss attributed to PN. Results: Forty-two patients underwent PN with mean pre-operative eGFR of 61.5 mL/min/1.73m2. The median total nephrometry score was 8, ranging from 4–10. Twenty-eight (66.7%) of the renal lesions were ≤ 4 cm, 13 (31%) were between 4 and 7 cm, and 1 (2.4%) was 〉 7 cm in diameter. The majority (54.8%) of the patients had tumors with more than 50% of tumor burden lying outside the expected renal border whereas 3 patients (7.1%) had tumors considered to be completely endophytic. Twenty-seven (64.3%) were within 4 mm of the collecting system. Tumor locations defined as: completely polar, interpolar, and completely central were assigned to 11, 15, and 16 lesions respectively. By post-operative month 6, the overall average eGFR of 53.9 mL/min/1.73m2 was significantly less (p = 0.0293) than the pre-operative value. However, we were unable to correlate change in post-operative eGFR with pre-operative total or individual R.E.N.A.L. scoring parameters. Conclusions: Neither the individual components of the R.E.N.A.L. nephrometry scoring system nor the total nephrometry score correlated with realized functional loss as assessed by eGFR in patients with a solitary kidney undergoing NSS.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 1-1
    Abstract: 1 Background: ILNM PSCC patients (pts) have heterogeneous outcomes. We aimed to identify risk factors of early recurrence in order to optimize the selection of pts for adjuvant (adj) therapies (tx). Methods: In a multicenter database of 924 pts who underwent ILN dissection, we identified 311 ILNM pts. Pts treated with neoadj chemo (CT) and/or radiotherapy (RT) were excluded. Multivariable Cox regression analyses (MVA) tested for predictors of recurrence, after adjusting for adj tx, age, type of surgery of the primary and smoking status. As primary endpoint, a risk calculator predicting early (24-month) risk of recurrence was developed. As secondary endpoint, the overall survival (OS) benefit of adj tx was examined according to the risk calculator-derived tertiles using Kaplan-Meier analysis. Results: Overall, 159 pts (51.1%) had pN1-2 and 203 (65.3%) pT2-4 disease. Overall, 195 (62.7%) and 78 (25.1%) received partial or total penectomy, whereas 6 (1.9%) local excision and 32 (10.3%) other procedures. Median number of removed and positive ILN were 15 (IQR 9-21) and 2 (IQR 1-3). Pelvic LND was performed in 154 (49.5%) pts, and 39% of them had pelvic LNM. In MVA, ILN ratio (HR: 1.01, p= 0.04), pN3 (HR: 2.53, p=0.002) and positive proximal margin of the primary (HR: 2.13, p=0.02) were significantly associated with recurrence. The c-index of our 3-variable risk calculator was 68%, with a net benefit higher that treat-all option from 20% to 90% threshold-probabilities. Within the cohort of adj CT and/or RT (N=127) pts, intermediate-high tertile had similar median OS (NR vs 107m) compared to pts in the low tertile (p=0.1). Conversely, intermediate-high tertile pts who received observation alone had shorter OS (NR vs 40m) compared to the same pts in the lower tertile (p 〈 0.001). Similar results were obtained for CT and RT separately analyzed. Conclusions: We developed and internally validated a risk calculator to predict early recurrence in ILNM surgically-resected PSCC pts. According to our risk-calculator, pts with intermediate/higher risk of early recurrence may benefit from adj tx. Our risk calculator can be used for counseling and enrolment in ongoing studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
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  • 5
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2015
    In:  Journal of Clinical Oncology Vol. 33, No. 7_suppl ( 2015-03-01), p. 394-394
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 33, No. 7_suppl ( 2015-03-01), p. 394-394
    Abstract: 394 Background: Penile carcinoma accounts for 0.4% to 0.6% of all malignancies in men. Due to its low incidence the prognostic role of clinicopathological characteristics, p16, p53 and HPV infection remains unclear. We report our experience with p16, p53 and HPV ISH (types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 66) in determining the aggressive nature of this carcinoma. Methods: A tissue microarray (TMA) of 57 cases of invasive penile squamous cell carcinomas was immunohistochemically stained with immunohistochemical stains p16 and p53. HPV ISH was performed as well. The TMA slides were scored semi quantitatively by a specialized genitourinary surgical pathologist. The H score was calculated for p53 using a combination of staining intensity and extent according to the following formula: H score = 1 x % of tumor cells with weak staining + 2 x % of tumor cells with moderate staining + 3 x % of tumor cells with strong staining, resulting in a total score of 0 – 300. Calculations for p53 were done considering values above 0 as positive. For p16 and HPV ISH, the results were recorded as negative or positive. The overall survival curves for up to 60 months were estimated by Kaplan-Meier (KM) method. Results: HPV ISH was positive in 23 cases and p16 was positive in 23 cases as well. However, there were 9 discordant cases between the two (p16+/HPV ISH- = 5; p16-/HPV ISH+ = 4). p53 was positive in 39 cases. Tumors positive for HPV ISH had a better survival as compared to HPV ISH negative tumors (p = 0.0040; Hazard ratio 4.991). Whereas p16 (p = 0.206; Hazard ratio 1.838) and p53 (p = 0.1582; Hazard ratio 0.5198) were not significantly associated with survival at 60 months. Conclusions: Overall HPV positive penile carcinomas appear to have a distinct biology with better prognosis. There is no significant difference in survival for tumors with different p16 and p53 expression.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2015
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  • 6
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 6_suppl ( 2017-02-20), p. 497-497
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 6_suppl ( 2017-02-20), p. 497-497
    Abstract: 497 Background: Although several guidelines outline management options for patients with renal masses, few studies describe treatment strategies and outcomes in octogenarians. We sought to review outcomes in this population managed with active surveillance (AS), partial nephrectomy (PN), or radical nephrectomy (RN). Methods: Data were collected on 113 octogenarian patients referred for management of renal masses at Moffitt Cancer Center between 2000 and 2013. Patients were treated with AS, PN, or RN. Univariate and multivariable Cox regression models measured association of management modality and survival. Kaplan-Meier survival analysis was used for overall survival and log-rank tests were used to compare survival curves. Covariates include age, Eastern Cooperative Oncology Group (ECOG) score, clinical and pathologic stage, tumor size, creatinine, creatinine clearance, and overall survival. Results: Out of 113 patients, 27 (22%) underwent AS, 33 (26.8%) underwent PN, and 53 (43%) underwent RN. The mean age was 83 years (range, 80-92). AS patients had a higher mean age (84 years) than PN patients (81.9 years), but not with RN patients (83 years) (p=0.008). At a median follow-up of 30.6 months (IQR 9.9-56), 13 (48%), 10 (30.3%), and 29 (54.7%) patients died from any cause in AS, PN, and RN patients respectively. PN patients tended to have a longer median overall survival at 81 months versus 55.8 and 57 months for AS and RN respectively, but this did not reach statistical significance on univariate (p=0.588) or multivariate analysis (p=0.29). On subgroup analysis of cT1a patients, there was also no difference in overall survival among treatment arms on univariate (p=0.654) and multivariate analysis (p=0.47). At 1 year follow-up, there was no difference in creatinine levels between treatment arms (p=0.331). However, mean creatinine clearance was lower in RN patients (35.8 ml/min) compared to AS (50.7 ml/min) and PN (48.1 ml/min) (p=0.024). Conclusions: Active treatment with PN and RN may not provide a survival advantage among octogenarians. Renal function was inferior in RN patients but comparable between AS and PN patients at 1 year follow-up.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 7
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 6_suppl ( 2021-02-20), p. 268-268
    Abstract: 268 Background: For metastatic renal cell cancer (mRCC) patients considering cytoreductive nephrectomy (CN), perioperative morbidity is important to discuss but few contemporary multi-institutional data are available. The objective of this study is to describe factors associated with perioperative outcomes in a modern multi-institutional cohort of patients treated with cytoreductive nephrectomy. Methods: Data for perioperative complications was recorded for patients treated with CN at 5 centers from 2005-2019. Postoperative complications within 90 days were categorized using Clavien- Dindo system. Univariate and multivariable analysis was used to evaluate for associations with complications and 90-day mortality. Factors evaluated included receipt of pre-surgical systemic therapy, ECOG performance status (PS), Charlson comorbidity index (CCI), concurrent IVC thrombectomy, age, and surgical approach (open vs. laparoscopic/robotic). Results: Perioperative outcomes were evaluated in 937 consecutive patients treated with CN at 5 institutions from 2005-2019. Median age at surgery was 61 years (IQR 53-68) and median tumor diameter was 9.8cm (IQR 7-12).Venous thrombus was present in 406/937 (43.3%) patients overall including 65/406 (16%) patients for whom IVC thrombus extended above the hepatic veins. Open and laparoscopic/robotic approach was used in 715 (76.3%) and 290 (23.4%) patients. The median ECOG PS was 1 (IQR 0-1) and median CCI was 1 (IQR 0-2). Pre-surgical systemic therapy was given to 243 (25.9%) patients prior to CN. The median length of hospital stay was 5 days (IQR 4-7) and 429 (34.6%) received blood transfusion. Median length of stay was 3.0 (IQR 2-4) for laparoscopic/robotic approach and 6 days (IQR 4-8) for patients with IVC thrombectomy. Hospital readmission within 30 days was identified in 112 (9.0%) patients. A total of 93/937 (9.9%) patients had major (≥Clavien 3) complications identified within 90 days postoperatively. On multivariable analysis, IVC thrombectomy was associated with higher risk of major complications OR 1.95 (95% CI 1.2-3.1), p = 0.006. Pre-surgical systemic therapy, ECOG PS, CCI, age and surgical approach were not associated with major complications (p = 0.09-0.85). Perioperative mortality was 12/937 (1.3%) at 30 days and 51/937 (6.7%) at 90 days. After multivariable analysis, pre-surgical systemic therapy, ECOG PS, CCI, age, and IVC thrombectomy were not associated with perioperative mortality (p = 0.1-0.85). Conclusions: Cytoreductive nephrectomy is associated with major complications for 10% of patients and 1% mortality at 30 days. Pre-surgical systemic therapy was not associated with increased risk of complications or mortality.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 1528-1528
    Abstract: 1528 Background: The COVID-19 pandemic has disrupted US healthcare delivery and led to delays in life-prolonging therapy for some conditions. Its impact on diagnosis and timely care delivery for patients (pts) with cancer is unknown. We assessed the pandemic’s impact on time from advanced diagnosis to systemic treatment initiation (TTI) for pts with newly diagnosed advanced solid cancers. Methods: We performed a controlled interrupted time series analysis using the nationwide Flatiron Health electronic health record-derived de-identified database, which originated from ̃280 US cancer clinics. The study sample included pts ≥ 18 years diagnosed with advanced solid cancers from Jan 1-Jul 31 in 2019 or in 2020, excluding a 30-day period (Mar 8-Apr 7) encompassing the start of most state stay-at-home orders. We used Cox proportional hazards models to estimate standardized predicted probabilities of TTI within 30 days of advanced diagnosis before (Jan-Mar) and during (Apr-Jul) the pandemic in 2020, compared to historical controls in 2019, adjusted for age, sex, race, insurance, performance status, and cancer type. Interactions by cancer type and race examined heterogeneity of effects. Results: The study included 12,977 pts (median age 69 yrs [IQR 61-77]; 47.4% female; 59.4% non-Hispanic white). At the time of analysis, fewer advanced cancer diagnoses were recorded in 2020 (Jan-Mar 2,409; Apr-Jul 3,027) than in 2019 (Jan-Mar 2,910; Apr-Jul 4,631). Compared to Apr-Jul 2019, pts diagnosed with advanced cancer during the COVID-19 period were more likely to have de novo (vs recurrent) disease (67.3% vs 56.8%). In adjusted models, the COVID-19 period was associated with an increased probability of treatment within 30 days (adjusted difference-in-differences +5.2 percentage points [ppts] ). TTI improvements were not observed for pts with advanced breast cancer or Black pts, but effect differences across subgroups were not statistically significant (Table). Conclusions: Among pts diagnosed with advanced cancer, the COVID-19 pandemic was associated with shorter time to systemic therapy initiation. These treatment patterns may reflect the fewer advanced cancer diagnoses and higher proportion of de novo cancers observed during this period. Longer follow-up and data maturity are needed to understand the impact of the pandemic on clinical outcomes.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e16535-e16535
    Abstract: e16535 Background: Immunohistochemistry (IHC) to determine PD-L1 expression level has been used as a biomarker to predict immune checkpoint inhibitors response in UCB. We hypothesized that the GA profiles would differ between UCB featuring high vs negative PD-L1 expression. Methods: 102 cases of advanced UCB with known PD-L1 tumor cell expression underwent hybrid-capture based comprehensive genomic profiling to evaluate all classes of genomic alteration (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Tumor cell (TC) PD-L1 expression was determined by IHC (Dako 22C3). Only PD-L1 high (H) (≥50% TC expression) and negative (N) (0% TC expression) cases were included in this study. Results: Overall, only 2 (8.3%) of the 24 PD-L1H UCB featured CD274 ( PD-L1) amplification (mean 19 copies) and none of 78 PD-L1N had CD274 amplification (P = .05). The gender, age and GA per tumor frequencies were similar in the groups. When compared with the PD-L1H UBC cases, FGFR3 GA were significantly more frequent in the UBC PD-L1N cases (p = .02). Currently “untargetable” GA that were more frequent in the PD-L1H UBC, but did not reach significance, included TP53, TERT and RB1. MTAP loss, a potential target for PRMT5 and MTA2 inhibitors, were 3X more frequent in the PD-L1N UBC. ERBB2 amplification and ERBB3 and PIK3CA short variant (SV) GA were more frequent in the PD-L1N UBC with differences not reaching significance. The mean gLOH scores were similar in both groups. Other ICPI-associated potential biomarkers, including MSI status, TMB level and GA in PBRM1, STK11 and MDM2 were not significantly different in the groups. For UCB cases where a mutational signature could be determined, 15/33 (45%) of PD-L1H and 34/112 (30%, p = 0.14) of PD-L1N UCB featured an APOBEC gene signature; 79% of PD-L1H and 83% of PD-L1N featured European ancestry (p = 0.61). Conclusions: PD-L1H and PD-L1N subtypes of UCB differ in their genomic profiles. PD-L1N UCB features greater frequencies of potentially “targetable” GA, including FGFR3, ERBB2, ERBB3 and PIK3CA. PD-L1 IHC may thus not only play a role in the selection of ICPI for advanced UCB but also in designing trials that may combine ICPI with targeted therapies.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 3130-3130
    Abstract: 3130 Background: Given that the clinical manifestations, disease course, and treatment options for pSCC differ between tumor types, we performed CGP to examine possible genomic differences. Methods: 1,741 clinically advanced pSCCs including 230 penile (penSCC), 17 male urethral (murthSCC), 125 male anal (manSCC), 7 female urethral (furthSCC), 263 vulvar (vulSCC), 822 cervical (crvSCC), and 277 female anal SCCs (fanSCC) underwent hybrid capture-based CGP to evaluate all classes of genomic alterations (GAs). Tumor mutational burden (TMB) was determined on up to 1.1 Mb of sequenced DNA and microsatellite instability (MSI) was determined on up to 114 loci. PD-L1 expression was determined by IHC (Dako 22C3). Results: HPV-16/18 detection was lowest in murthSCC and vulSCC and highest in manSCC, fanSCC, and crvSCC. TP53 GAs were inversely associated with HPV status. PIK3CA GA frequency varied (22-43%). DNA-damage response (DDR) GAs (e.g., BRCA1/2, ATM, others) were low ( 〈 1-3%) throughout. Cell-cycle GAs were most frequent in external cases (penSCC, furthSCC, vulSCC). MTOR pathway GAs ( PTEN, FBXW7) were the most frequently identified “actionable” GAs. FGFR3 GA were present in 〉 5% of murthSCC, crvSCC, and fanSCC; other receptor-tyrosine kinase (RTK) targeted options were 1% in BRAF/ ERBB2. NOTCH1 GAs were present in 〉 15% of penSCC and vulvSCC. TMB ≥10 mut/Mb was 〉 15% in manSCC, fanSCC, and crvSCC. PD-L1 low expression was 〉 25% in all pSCC except crvSCC and high expression was 〉 18% in all pSCC except urthSCC and manSCC. Conclusions: Despite similar histology, pSCC differ widely in GAs and HPV status. PIK3CA is the most frequent “targetable” GA followed by MTOR pathway and cell cycle; RTK targets are extremely rare. PARP inhibitor options appear low given the infrequent finding of DDR GAs. Anti-PD(L)1 could be considered in a number of cases based on TMB 〉 10 mut/Mb and PD-L1 expression.[Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
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