bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors of clear renal cell carcinoma in pT1a cases
Authors: Nishikimi T. , Tsuzuki T. , Fujita T. , Sassa N. , Araki H. , Fukatsu A. , Katsuno S. , Yoshino Y. , Hattori R. , Gotoh M. 
Published: August 2020

e16064 Background: The proportion of clear cell renal cell carcinoma (CRCC) cases diagnosed at pT1a is known to be increasing significantly. Although their prognosis is excellent in general, some cases show distant metastasis. Most of proposed prognostic factors are based on mainly large sized CRCC data. The prognostic factors for small sized CRCC, especially for pT1a cases, aren't well described. Methods: Three hundred three pT1a CRCC cases were retrieved from authors’ institution files. All cases were reviewed by the single uropathologist (T. Tsuzuki). For each case, the following pathological parameters were analyzed: patient age, tumor location (upper, middle, low), Furhman grade, presence of capsule, presence of lympho-vascular invasion, growth pattern (expansive or infiltrating), presence of scar, presence of hemorrhage, and presence of necrosis. Results: Male to female ratio was 4.4. Patient's age ranged from 21 to 85 years (median: 59 years). Follow up duration ranged from one to 225 months (median: 59 months). 35 cases showed distant metastasis. The 5-year and 10-year cause specific survival rate were 96.9%, 93.0%. The 5-year and 10-year recurrence free survival rate were 91.8%, 83.9%. Furhman grade (grade 1+2+3 vs. 4), presence of lympho-vascular invasion, infiltrating growth pattern, and presence of necrosis were statistical significant (p < 0.0001). Conclusions: Furhman grade (less than 3 vs. 4), presence of lympho-vascular invasion, growth pattern, and presence of necrosis can be prognostic factors in CRCC in pTa cases. Growth pattern, which is unrecognized concept for prognosis, can be a new prognostic factor in CRCC. No significant financial relationships to disclose.
External validation of a nomogram predicting survival in men with metastatic hormone-refractory prostate cancer
Authors: Gravis G. , Walz J. , Bagattini S. , Esterni B. , Mimoun C. , Salem N. , Marcy M. , Brunelle S. , Viens P. , Bladou F. 
Published: August 2020

e16066 Background: Armstrong et al. (Clin Cancer Res. 2007;13:6396–403) recently published a nomogram predicting the probability of survival in patients with hormone-refractory prostate cancer. The initial report showed a predictive accuracy of 0.69. So far, this nomogram was not yet externally validated. We validated this nomogram in a cohort of patients with hormone-refractory prostate cancer participating in five phase II trials. Methods: In our institution, 84 patients received chemotherapy for metastatic symptomatic hormone-refractory prostate cancer from September 1999 to November 2006. Follow-up was stopped in March 2008 and median follow up for all patients was 15.7 month. 75% of patients received docetaxel based chemotherapy. At the time of inclusion, median age was 69.0 years, median PSA was 40ng/ml, 93% had known bone metastases and 19% had visceral metastases. The area under the receiver operating characteristics curve was used to estimate the predictive accuracy of the nomogram and calibration plots were used for comparison between predicted and observed probabilities. Results: Of all patients, median survival was 15.5 month. The nomogram predicted median survival was 19.9 month, overestimating the true survival by roughly 30%. The predictive accuracy of the predictions at 1 year, 2 years and 5 years was 0.76, 0.69 and 0.64, respectively. The calibration plots showed departures from ideal predictions at 1 year (up to 20% of over estimation of true survival) and 5 years ( up to 19% of under estimation of true survival), whereas the predictions at 2 years showed almost perfect calibrations. Conclusions: The Armstrong et al1 nomogram provides accurate survival predictions in patients with hormone-refractory prostate cancer. The current external validation of this nomogram provides evidence that the nomogram might generally be applied to those patients in daily practice. No significant financial relationships to disclose.
Impact of VEGF and CgA as new predictive tools in management of elderly hormone-refractory prostate cancer (HRPC) patients
Authors: Carreca I. , Bellomo F. , Burgio S. , D'Alia P. , Piazza D. , Russo S. , Balducci L. 
Published: August 2020

e16070 Background: Prostate cancer is one of the most frequent malignancy in men of the Western countries. The identification of new predictive factors of drug activity is crucial for elderly cancer patients, who need a particular selection according to prediction of efficacy and safety by pre-treatment parameters. Several prostate cancers show focal neuroendocrine (NE) spots and CgA seems to be associated to NE phenotype both in tissue and in circulation. VEGF expression in NE cells is corelated with clinical characteristics and disease-specific survival. Somatostatin analogues induce a decrease in plasma CgA and could have also anti-angiogenic activity by inhibition of VEGF, bFGF and GH/IGF-I axis. Methods: elderly patients, median age 75 (range: 65–83), were selected for hormone-refractory disease, previously treated with CAB. Serum PSA and plasmatic CgA and VEGF were evaluated in all pts at baseline (T0) and at 4 months (T4) and 8 months (T8) after therapy. Pts were treated with docetaxel 75 mg/m2 every 3 weeks for 6 cycles and octreotide acetate 20 mg administered intramuscularly every 4 weeks until progression. Clinical and biochemical response, progression- free survival and toxicity were also evaluated. A correlation of basal CgA and VEGF with biochemical response, clinical response and clinical benefit was also investigated. Results: Median duration of follow-up was 18 months (range: 8–32). Patients evaluable for response were 22. PSA response rate (RR) was observed in 10/22 (45%); clinical objective RR was 33% (7/22). Clinical benefit was observed in 19/22 pts (86%). Only mild toxicities was observed in both groups. CgA and VEGF were both strongly reduced after therapy. Lower CgA values correlated with clinical benefit, lower VEGF values also correlated with biochemical and clinical response. Conclusions: This combination treatment showed a good toxicity profile. The most relevant data in this study refer to the role of serum CgA and VEGF levels, for prediction of tumour response. If these findings were confirmed, it could be sufficient to measure these markers levels for identification of those HRPC patients who have more probability of obtaining clinical benefit from a docetaxel-based treatment in combination with a somatostatin analogue. No significant financial relationships to disclose.
Complications of postchemotherapy residual tumor resection in patients with germ cell cancer
Authors: Albers P. , Bingöl C. , Witthuhn R. , de Geeter P. 
Published: August 2020

e16077 Background: Residual tumor resection (RTR) is mandatory in all patients with advanced germ cell tumors and visible residual disease after chemotherapy. Full bilateral RTR is the proposed standard of care. However, in lately published series, the rate of nerve-sparing procedures was only 40%. Stage-related RTR may decrease surgical complications, enhance the rate of postoperative antegrade ejaculations and may not compromise oncological efficacy. Methods: A retrospective analysis of 98 patients in a tertial referral center with RTR (2003–2008) was performed using the RTR database and patients´ charts to correlate the extent of surgery to complications and outcome. Results: 49% of patients initially had IGCCCG intermediate and poor prognosis features. In 34%, residual tumor diameter was >5 cm. With a median age of 33 yrs (17–65), the median time of surgery was 210 min (90–604) with a median blood loss of 500 cc (50–5000). In 25 of 98 patients a full bilateral RTR was necessary to remove all residual tumors. The median residual tumor diameter in patients with full bilateral RTR without nerve-sparing was 10.9 cm (1.5–30) as opposed to 4.3 cm (0.5–20) in patients with modified template and/or nerve-sparing approaches (not significant). In 10 pts a nephrectomy and in 9 pts a resection of the vena cava was necessary. Only 2 of each had a bilateral RTR. All CTCAE grade III/VI complications like intraoperative hemorrhage (n=25, 11/25 bilateral RTR), postoperative lymphocele (n=8, 6/8 bilateral RTR), and retrograde ejaculation (15% with modified template and/or nerve-sparing, 100% with bilateral RTR) were significantly correlated with the residual tumor size and with the field of resection. Four patients relapsed, one had an in-field relapse after a template resection. One patient died due to a postoperative aorto-duodenal fistula. Conclusions: The complication rate of RTR is strongly related to the median residual tumor size and the extent of surgery. A full bilateral resection in all patients may result in unnecessary complications in a considerable cohort of patients. The field of resection should be adapted to the primary localization of disease and full bilateral resections should be performed only in patients with bilateral disease. No significant financial relationships to disclose.
Cisplatin (C) and gemcitabine (G) chemotherapy with concurrent irradiation (XRT), for the conservative treatment of invasive transitional bladder cancer (ITBC) patients: Clinical outcome and long-term follow-up in a monoinstitutional experience
Authors: Caffo O. , Fellin G. , Graffer U. , Mussari S. , Caldara A. , Murgia V. , Valduga F. , Tomio L. , Galligioni E. 
Published: August 2020

e16081 Background: C and G have synergistic activity when used in combination and are both potent radiosensitizers. In a dose finding trial, conducted in our hospital on ITBC patients using C and G with concurrent XRT, after maximum transurethral resection (TUR), the maximum tolerated dose of G was 400 mg/sqm (IJROBP 2003). On this basis, we have designed a phase II trial, which was prematurely closed, due to low accrual. We are presenting the long-term clinical outcome of the 16 patients involved in the dose-finding trial, together with that of the 9 pts enrolled in the phase II study. Methods: From June 1999 to December 2004, we have treated in our institution a consecutive series of 25 T2–4 N0 ITBC pts (median age 67 yrs, range 51–80). After macroscopically radical TUR, all pts received XRT (54 Gy in 30 fractions over 6 weeks) and concurrent C (100 mg/sqm, days 1, 22). In dose finding study G was given weekly from 200 to 500 mg/sqm: since unacceptable toxicity was observed in 2 cases (one death for toxicity) at the higher dose level, the recommended G dose for phase II trial was 400 mg/sqm on day 1,8 q 21 for 2 courses together with C and XRT. A cystoscopic re-evaluation was scheduled 6–8 weeks after treatment. Results: Except the pt died during treatment for toxicity, all the remaining 24 pts were microscopically disease free at cystoscopic re-evaluation. Seven local and 2 distant relapses have been observed so far, at a median follow-up of 66 mos. Presently, 16 pts (67%) is alive and disease-free, with 1 patient died for lung cancer. All pts alive have retained their bladder, with a normal organ function, in absence of any relevant long-term toxicity. The median survival has not been reached yet, while the OS at 7 years is 66%. The 5-year DFS, local DFS and survival without cystectomy, were 62%, 70%, and 95%, respectively. Conclusions: In our experience G + C with concurrent XRT in ITBC pts, appears encouraging, even at a long-term follow-up. Considering the 100% of complete response observed, this combination could be of interest to explore a possible enhancement of the disease control of C plus XRT, that is today the treatment of choice in the conservative therapy of ITBC. No significant financial relationships to disclose.
High-dose chemotherapy and stem cell support in the management of metastatic germ cell cancer: A quantitative review
Authors: Bozcuk H. S. , Ozdogan M. , Coskun H. S. , Mutlu H. , Kargi A. , Uysal M. , Savas B. 
Published: August 2020

e16094 Background: To analyze the independent associates of outcome in metastatic germ cell cancer (MGCC) patients treated with high dose chemotherapy (HDC) and stem cell rescue. Methods: Thirty-two published patient cohorts with MGCC (encompassing 2176 patients; 510 patients treated upfront and 1666 at relapse) were identified from PUBMED and Cochrane Registry of Clinical Trials. Weighed Regression Analyses of these trials were conducted to define prognosticators. Results: Correlate of overall survival (OAS) and survival with no evidence of disease (NED) in upfront HDC trials was number of chemotherapeutics in HDC (OAS with 2 agents: 60% vs. 3 or more agents: 72%, p = 0.047, survival with NED with 2 agents: 47% vs. 3 or more agents: 64%, p = 0.009). In trials of HDC at relapse, independent associates of OAS with multivariate analysis were line of chemotherapy index, an indicator of line of chemotherapy utilization (p = 0.004), and median age (≤30: 42%, >30: 49%, p = 0.023), whereas independent correlates of better survival with NED were again number of chemotherapeutics in HDC (2 agents: 54% vs. 3 or more agents: 33%, p = 0.001), and seminoma fraction (seminoma fraction ≤9%: 28% vs. seminoma fraction >9%: 49%, p < 0.001 ). Toxic mortality of HDC regimens employed in these trials ranged between 0% and 17%. Conclusions: HDC can cure patients with MGCC both as initial or salvage therapies. However, this study shows that type and setting of HDC, as well as patient age, and seminoma fraction all appear to be linked with benefit from HDC in MGCC. Future trials should continue to address the usage of tandem HDC cycles with multiagent protocols in high risk patients with MGCC. No significant financial relationships to disclose.
Cancer testis antigen expression and immune responses by prostate cancer patients: Implications for prognosis and immunotherapy
Authors: von Boehmer L. , Wild P. , Keller L. , Hermanns T. , Provenzano M. , Sais G. , Jaeger E. , Stenner F. , Moch H. , Knuth A. 
Published: August 2020

e16101 Background: Prostate cancer (PC) is the most frequent malignancy in men and it continues to be one of the most common fatal cancers. Treatment options in advanced castration-resistant prostate cancer (CRPC) are limited. Cancer testis (CT) antigens are expressed in a variety of human cancers, but not in normal tissues except for MHC deficient spermatogonia, and represent promising targets for immunotherapy. Little is known about CT antigen expression in relation to disease progression. The aim of this study was to investigate which CT antigens are expressed and immunogenic and hence represent promising targets for patients with prostate cancer and correlate these findings with clinicopathological characteristics. Methods: To determine the expression of 6 CT antigens in prostate cancer immunohistochemistry was performed on tissue micro arrays. We investigated 6 CT antigens (NY-ESO.1, MAGE-C1, MAGE-C2, GAGE, MAGE-A1 and MAGE-A4) in benign hyperplasia (n=45), early (n=388) and late stage (n=71) prostate cancer. To determine the occurrence of spontaneous antibodies against cancer testis antigens, ELISA and Western blot was performed for NY-ESO-1, MAGE-C1 and MAGE-C2 with sera from prostate cancer patients. Results: CT antigens are increasingly expressed in late stage prostate cancers. As an exception we found MAGE-C2 to be expressed early in the course of disease, frequently inducing MAGE-C2 specific antibodies. In later stage metastatic prostate cancer patients NY-ESO-1 is more often expressed, inducing NY-ESO-1 specific antibodies. Conclusions: Cancer testis (CT) antigens are prognostic markers, frequently inducing immune responses and may be suitable for immunotherapeutic intervention in patients with prostate cancer. No significant financial relationships to disclose.
Down-staging of locally advanced prostate cancer with anti-CTLA-4 monoclonal antibody prior to radical prostatectomy
Authors: Granberg C. , Thompson R. H. , Quevedo J. F. , Karnes R. J. , Frank I. , Kwon E. D. , Blute M. L. 
Published: August 2020

e16103 Background: At present, androgen ablation (AA) therapy ± radiation therapy represents a first-line treatment for patients with unresectable locally advanced prostate cancer (CAP), typically resulting in palliative disease control. Immunotherapy, in the form of CTLA-4 blockade, has been shown to potentiate T-cell responses, representing a potential antitumoral immunotherapy for treating CAP. Here, we discuss the outcomes of 5 locally advanced CAP patients treated with the monoclonal antibody MDX-CTLA-4 (MDX-010) + AA who subsequently underwent radical prostatectomy (RP), 2 of whom exhibited striking down-staging of their disease. Methods: A Phase II trial testing AA + MDX-010 therapy for treatment of locally or systemically advanced CAP is currently ongoing at our institution. To date, 5/85 patients have electively opted for off-study RP with extended pelvic lymphadenectomy after documentation of robust treatment response by PSA, staging digital rectal exam, and 3-D imaging. Results: All men had unresectable, locally advanced disease (stage T2c-T4) prior to treatment with AA + MDX-010 and subsequently underwent RP. Median blood loss was 400mL (400–900). All patients had negative surgical margins. Of the 5 patients, 2 exhibited dramatic and indisputable down-staging of their disease. These two patients presented with 80% of biopsies involved with cancer, extraprostatic extension, seminal vesicle (SV) invasion, and bladder base involvement. On final pathology, both exhibited extensive treatment effect, remission of SV involvement, and robust disaggregation of solid tumors resulting in only microscopic, non-contiguous foci of residual intraprostatic cancer. Both had T4 disease pre-treatment, and had stage T2c on final pathology. One patient is free of disease with undetectable PSA for 19 months following adjuvant radiation treatment but no further therapy, while the other patient is awaiting follow-up. Conclusions: We have been able to demonstrate true down-staging of locally advanced prostate cancer with neoadjuvant AA + MDX-010 therapy. This therapeutic modality exhibits significant promise for men with unresectable disease and may provide durable and potentially curative cancer control. No significant financial relationships to disclose.
Predictive factors associated with clinical outcome and safety in Korean patients with metastatic renal cell carcinoma treated with sunitinib
Authors: Hong M. , Jeung H. , Chung H. , Ahn J. , Roh J. , Noh S. , Rha S. 
Published: August 2020

e16111 Background: Sunitinib has become a standard treatment for metastatic renal cell carcinoma (RCC). The research for identifying patients who are more likely to benefit from this agent is quite limited, especially in Asian patients. Methods: In total, 81 histologically proven metastatic RCC patients who were treated with sunitinib were reviewed between Jan 2006 and Dec 2008. Tumor response was evaluated according to the RECIST criteria, and safety was assessed by NCI-CTC (version 3.0). Primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), overall response rate (ORR), disease control rate (DCR), and toxicities. Clinical features associated with clinical outcome were identified by univariate analysis; then, a stepwise modeling approach based on Cox's proportional hazards regression was used to identify independent prognostic factors to these endpoints. Results: Median age was 58 years (range, 29 to 73), and 33 patients received sunitinib as first-line systemic treatment. Clear cell type was predominant (85%). Patient distribution was 12% for favorable, 78% for intermediate, and 10% for poor group according to the MSKCC risk group. With the median follow-up of 26 months, median PFS was 16 months (95% CI, 8 –24) and median OS was 24 months (95% CI, 18 –30). ORR was 30% (95% CI, 19–40%) and DCR was 80% (95% CI, 70–89%). The most common grade 3/4 adverse events of sunitinib was thrombocytopenia (32%). Other severe toxicity included neutropenia (21%), anemia (19%), leucopenia (14%), fatigue (10%), stomatitis (10%). In multivariate analysis, the previous exposure to immunotherapy was related to longer PFS (P<.012). Performance status (ECOG 0–1) and corrected Ca level (8.5∼10.5 mg/dl) were associated with favorable ORR (P=.038) and DCR (p=0.008), respectively. Predictive factors for grade 3/4 thrombocytopenia were corrected Ca level (P=.018), poor MSKCC risk group (P=.025), and low WBC count (<4500/ul, P=.041). Conclusions: Compared to western reports, our data demonstrated comparable clinical efficacy in Asian patients, but different safety profile, especially in hematologic toxicities. This approach provides a tailored approach to predictive factors for targeted agents. No significant financial relationships to disclose.
Treatment of poor-risk metastatic renal carcinoma patients with combination gemcitabine, capecitabine, and bevacizumab at a tertiary cancer center
Authors: Miller L. , Lal L. S. , Tannir N. M. , DaCosta Byfield S. , Atkinson B. , Feng C. , Lau J. K. , Yin L. , Jonasch E. 
Published: August 2020

e16112 Background: Treatment of poor risk metastatic renal carcinoma (mRCC) is challenging, and empiric combinations may be attempted in practice once conventional therapies fail. These combinations may lead to formal clinical trials. Evaluation of mRCC patients given an empiric combination of gemcitabine (gem) capecitabine (cap), and bevacizumab (bev) at a tertiary care center was performed. Methods: After obtaining IRB approval, non investigational use of gem in combination with cap and bev in mRCC patients was identified using institutional databases. Collected data included demographics, previous therapies, number of metastatic sites, MSKCC risk stratification variables, prior nephrectomy status, drug therapy duration, and progression-free survival (PFS). Descriptive statistics were employed for data analysis. Results: Thirty-six patients were included in the analysis, with a median age of 55.5 years. Seventeen patients (47%) had previously received a tyrosine kinase inhibitor (TKI). Twenty-two patients (61%) had clear cell histology, 13 patients (36%) had sarcomatoid features, 20 patients (56%) had undergone previous nephrectomy, 20 patients (56%) had four or more sites of metastasis and 27 patients (75%) were diagnosed within 1 year of therapy. Initial treatment consisted of gem (908.61 mg/m2) every 2 weeks, cap (2.75 grams/day), and bev (828.82 mg) every 2 weeks. The median PFS for the study population was 5.83 months. The subset of TKI patients had a median PFS of 5.4 months. Therapy was relatively well tolerated with only 3 patients discontinuing one or more of the drugs due to adverse reactions. Thirteen of the patients started a TKI post discontinuation of the triple therapy. Conclusions: The triple therapy combination in this retrospective evaluation provides promising efficacy and acceptable tolerability in patients with poor prognosis mRCC. Based on these observations, a phase II is now underway assessing gemcitabine, capecitabine and becacizumab in patients with sarcomatoid RCC. [Table: see text]