Prognostic impact of clinical and pathologic criteria in neuroendocrine and aggressive variant prostate cancer.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 268-268
Author(s):  
Beerinder S. Karir ◽  
Panagiotis J. Vlachostergios ◽  
Paul J. Christos ◽  
Victor RA Febles ◽  
Kavya Pinto-Chengot ◽  
...  

268 Background: Various clinical and pathologic criteria have been proposed to identify neuroendocrine (NE) or aggressive variant (AV) prostate cancer (PC). We assessed the prognostic value of clinical parameters in a single-institution cohort. Methods: An IRB-approved database was screened for clinical and/or pathologic criteria (Table 1) for NE/AV PC. Patients with advanced CRPC not meeting any of the criteria served as contemporary controls. Overall survival (OS) for each group was assessed using Kaplan-Meier method and comparisons with log-rank test. Results: 249 men were identified, median age 71.5 (45.1-90.8 years). 145 patients met at least 1 criterion suggestive of NE/AV PC, whereas 104 were CRPC only. Median OS for each subgroup, the combined NE/AV PC group, and the CRPC cohort are provided in Table 1. OS for NE/AV PC vs. CRPC cohort was 25.4 vs 33 months (p = 0.26). Patients with parenchymal brain metastasis had the worst survival of 5.2 mo [95%CI 2.1, 8.3]. On multivariate analysis, bulky high-grade disease in prostate/pelvis carried the highest risk of death (HR 1.71 [1.07, 2.74; p = 0.02]). Conclusions: A number of clinical and pathologic criteria have been used to define NE/AV PC for clinical practice or trial enrollment. Some criteria are associated with a shorter survival than others. Additional studies are warranted to further define both prognostic and molecularly defined subgroups. [Table: see text]

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7597-7597 ◽  
Author(s):  
Scott Alan Dorroh ◽  
Eric R Siegel ◽  
Rangaswamy Govindarajan

7597 Background: Platinum and etoposide chemotherapy is the treatment for patients with SCLC. O etoposide is substituted for IV by many clinicians at twice the dose for bioavailability but the outcome of these subjects has not been studied. To compare the efficacy of O vs. IV etoposide in extensive stage SCLC, a retrospective analysis of subjects treated in the VISN 16 network of 10VA hospitals was undertaken. Methods: Subjects with SCLC diagnosed between 10/1/1996 and 9/30/2010 were identified from the VISN-16 tumor registry. Study was limited to extensive disease by excluding those treated with radiation therapy. Chemotherapy details were obtained from the pharmacy data in the VISN 16 database. Overall survival (OS) was computed as the time in months from the first etoposide issue date to the date of death or last contact. Kaplan-Meier methods were used to compute median OS, and etoposide groups were compared via log-rank test. Results: 300 subjects were eligible for analysis, with median age 67 yrs (range 45-84). 295 deaths were observed during 2,419 total months of follow-up. The median OS of all subjects was 6.3 months (interquartile range (IQR) 2.0-11 months). In addition to platinum, 153 subjects received only O etoposide, 147 received some form of IV etoposide. The median duration (IQR) of therapy for all subjects was 29 (1-110) days; 23 days for those who received any IV etoposide and 43 days for those who received only oral etoposide. The median OS was 7.6 months for those who received only O etoposide vs. 5.4 months for any IV etoposide (P<0.0001). In the latter group, those receiving purely IV etoposide had only 1.5 months’ median OS vs. 8.8 months for those receiving both O and IV etoposide (P<0.0001). Conclusions: Survival of subjects with SCLC treated with O etoposide is comparable to those who received a combination of O and IV therapy. Poor OS for those with only IV therapy may be due to selection bias of poor-performance subjects. [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15756-e15756 ◽  
Author(s):  
Leszek Kraj ◽  
Andrzej Śliwczyński ◽  
Joanna Krawczyk-Lipiec ◽  
Krzysztof Woźniak ◽  
Anna Waszczuk-Gajda ◽  
...  

e15756 Background: Preclinical studies have shown that calcium channel blockers (CCB) may potentiate anticancer effect of chemotherapy via intra-cellular drug accumulation. Gemcitabine-based chemotherapy is commonly used in pancreatic cancer (PC) patients. The aim of this study was to determine whether CCB may affect overall survival (OS) in PC patients receiving gemcitabine-based chemotherapy. Methods: The retrospective cohort of PC patients treated with gemcitabine between 2007 and 2016 was identified in the Polish National Health Fund databases. Electronic records of prescriptions were searched to identify in this cohort patients receiving CCB (amlodipine, nitrendipine, felodipine, lacidipine). The primary endpoint was OS and it was determined by Kaplan-Meier methods and compared by the log-rank test. Results: In total 4628 PC patients treated with gemcitabine (median OS 7.7 months; 95% CI: 7.4-7.9) were identified. Among these 380 patients were prescribed any CCB. There was a significant difference (p < 0.001) in median OS between patients prescribed CCB (n = 380; OS 9.3 months; 95% CI: 7.8-11.0) and those who did not (n = 4214; OS 7.6 months; 95% CI: 7.3-7.8) with hazard ratio for death 0.70 (95% CI: 0.62-0.79). Notably, the survival curves tended to flatten in CCB group, with 24% of patients alive at 2 years (95% CI: 20-29%) and 15% alive at 5 years (95% CI: 11-19%), compared with 11% (95% CI: 10-12%) and 4% (95% CI: 4-5%) in controls respectively. Conclusions: The use of CCB in PC patients receiving gemcitabine-based chemotherapy was associated with improved OS. Further validation is needed to evaluate effectiveness of CCB-gemcitabine combinations in the management of PC.


Cancers ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 1319 ◽  
Author(s):  
Hendriksma ◽  
Ruler ◽  
Verbist ◽  
Jong ◽  
Langeveld ◽  
...  

Background: Local recurrence after radiotherapy for T2 glottic carcinoma remains an issue and identifying patients at risk for relapse is, therefore, important. This study aimed to assess the oncological outcomes and prognostic factors in a consecutive series of patients treated with radiotherapy for T2N0 glottic carcinoma. Methods: Patients with T2N0 glottic carcinoma treated with radiotherapy were included in this retrospective study. Five- and ten-year local control (LC), overall survival (OS), disease-specific survival (DSS), and laryngeal preservation (LP) rates were calculated with the Kaplan–Meier method. The impact of prognostic variables was evaluated with the log-rank test. Results: Ninety-four patients were included for analysis. LC, OS, DSS, and LP rates were 70.5, 63.7, 86.0, and 74.7%, respectively at five years and 65.8, 41.0, 75.6, and 72.4% at 10 years. In total, 46 scans were included in the analyses. Vertical involvement of the anterior commissure on imaging showed a significant impact on LC. Conclusions: In accordance with previously described surgical risk factors, we identified vertical involvement of the anterior commissure on imaging as a prognostic factor for radiation failure.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9528-9528
Author(s):  
Brendan D. Curti ◽  
Gregory A. Daniels ◽  
David F. McDermott ◽  
Joseph Clark ◽  
Howard Kaufman ◽  
...  

9528 Background: IREs are associated with immunotherapy (IT) for cancer and while reports suggest improvement in TC and OS with induced IREs, the long-term impact is unclear. IL2 has been the major IT for patients (pts) with renal cell carcinoma (RCC) and melanoma (MM) since 1992. We evaluated IREs reports in the PROCLAIMSM data base (2008-2016) of IL2-treated pts. Methods: Reports on 614 (MM) and 843 (RCC) pts were queried for IREs. IREs were categorized as occurring before, during, or after IL-2 and related to any checkpoint inhibitor (CPI). TC (CR+PR+SD) was compared between no IRE and IRE, using Fisher’s exact test. OS curves were estimated by Kaplan-Meier method, and comparison of no IRE/before IL2 with during/after IL2, was analyzed by log-rank test. Results: With a median (med) follow-up of 3.5+ years (range 1-8+ year), 140 IREs were reported in 118 pts (9.6% of all PROCLAIMSM pts): 93 (15%) in MM; 47 (5.6%) in RCC. 25 IREs were prior to IL2; 13 IREs were during IL2; 102 were after IL2. Of the latter 102, 31 were after IL2 and after subsequent CPI; 71 were attributed to IL2 only; and in 13, IREs were due to either IL2 or CPI. TC was 73% for IRE group vs 56% for no IRE group (p = 0.0054). OS was significantly greater for IRE group during/after IL2 compared to no IRE/before IL2 in MM, med 46 months (mo) vs 18 mo (p = 0.0001) and in RCC, med 61 mo vs 43 mo (p = 0.0196), independent of CPI IREs. Med # of IL2 doses was 19 in no IRE group, 39 in IRE during IL2 group, and 25 in IRE after IL2 group. IL2-related IREs were primarily vitiligo and thyroid dysfunction (70% of IL2 IREs), with limited further impact, while CPI-related IREs were often serious, requiring intervention (hypophysitis, colitis, hepatitis, uveitis) (52% of CPI IREs) and possibly chronic management. Conclusions: IREs following IL2 are associated with improved TC and OS. IREs resulting from IL2 and from CPIs are qualitatively different and likely reflect different mechanisms of action of immune activation and response.


Author(s):  
Keiichiro Mori ◽  
Vidit Sharma ◽  
Eva M. Comperat ◽  
Shun Sato ◽  
Ekaterina Laukhtina ◽  
...  

Abstract Background Grade group (GG) 4 prostate cancer (PC) is considered a single entity; however, there are questions regarding prognostic heterogeneity. This study assessed the prognostic differences among various Gleason scores (GSs) classified as GG 4 PC on biopsy before radical prostatectomy (RP). Methods We conducted a multicenter retrospective study, and a total of 1791 patients (GS 3 + 5: 190; GS 4 + 4: 1557; and GS 5 + 3: 44) with biopsy GG 4 were included for analysis. Biochemical recurrence (BCR)-free survival, cancer-specific survival, and overall survival were analyzed using the Kaplan–Meier method and the log-rank test. Logistic regression analysis was performed to identify factors associated with high-risk surgical pathologic features. Cox regression models were used to analyze time-dependent oncologic endpoints. Results Over a median follow-up of 75 months, 750 patients (41.9%) experienced BCR, 146 (8.2%) died of any causes, and 57 (3.2%) died of PC. Biopsy GS 5 + 3 was associated with significantly higher rates of GS upgrading in RP specimens than GS 3 + 5 and GS 4 + 4. On multivariable analysis adjusted for clinicopathologic features, different GSs within GG 4 were significantly associated with BCR (p = 0.03) but not PC-specific or all-cause mortality. Study limitations include the lack of central pathological specimen evaluation. Conclusions Patients with GG 4 at biopsy exhibited some limited biological and clinical heterogeneity. Specifically, GS 5 + 3 had an increased risk of GS upgrading. This can help individualize patients’ counseling and encourage further study to refine biopsy specimen-based GG classification.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18125-e18125
Author(s):  
Eduardo Richardet ◽  
Martin Eduardo Richardet ◽  
Nicolas Castagneris ◽  
Matias Nicolas Cortes ◽  
Perelli Laura ◽  
...  

e18125 Background: Platinum based regimens are standard first-line treatment in patients with advanced non mall cell lung cancer. We intend to evaluate their effectiveness according to the number of cycles administered, and investigate whether histology is a predictor of benefit from a greater number of infusions. Methods: 124 patients with stage IV NSCLC were evaluated retrospectively. They were divided according to whether they made 4 or 6 cycles of chemotherapy. The schemes used were: Cisplatin / Gemcitabine and Carboplatin / Paclitaxel, at standard doses. We studied the efficacy in both groups according to the most common histologies (adenocarcinoma and squamous cell carcinoma). PFS (progression-free survival) and OS (overall survival) were calculated by the Kaplan-Meier curves and compared by the Log Rank Test. Results: Those who underwent 4 cycles had a PFS of 7.77 months and OS of 12.2 months vs. 8.64 and 10.8 months those who received 6 cycles (p = 0.47, p = 0.76). Within the subgroup with squamous histology (n = 43), PFS and OS were 7.38 and 13.38 months respectively in the group that received 4 cycles vs. 7.97 and 9.76 months in those receiving 6 (p = 0.70, p = 0.32 ). Within adenocarcinoma histology (n = 81), those who received 4 cycle, has a PFS of 8.17 months and they lived 11.56 month, vs 8.96 and 10.79 months for those receiving 6 cycles (p = 0.29, p = 0.88) Conclusions: In our population, a greater number of cycles showed no advantages in terms of progression-free survival or overall survival. Histology is not a predictive factor for deciding how many chemotherapy cycles administer.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 8031-8031
Author(s):  
Wilson I. Gonsalves ◽  
Dragan Jevremovic ◽  
Angela Dispenzieri ◽  
Francis Buadi ◽  
David Dingli ◽  
...  

8031 Background: Our prior studies identified the prognostic significance of ≥400 cPCs/150,000 analyzed events quantified by MFC in NDMM. We evaluated if a similar quantification of cPCs using MFC can add prognostic value to the current R-ISS classification of NDMM pts. Methods: We evaluated all NDMM pts seen at the Mayo Clinic, Rochester from 2009-2017 who had their peripheral blood samples evaluated by 6-color MFC prior to therapy. The cPCs detected were reported as the number of clonal events/150,000 collected total events. Survival analysis was performed by the Kaplan-Meier method and differences assessed using the log rank test. Results: This cohort consisted of 566 consecutive pts with NDMM with a median age of 66 years (27-95). The distribution of the R-ISS classification of this cohort is as follows: Stage 1- 128 (23%) pts, Stage 2- 369 (65%) pts and Stage 3- 69 (12%) pts. The median number of cPCs was 59 (0-46,412) / 150,000 events. The median time-to-next-treatment (TTNT) and overall survival (OS) for pts with ≥400 cPCs (n = 140, 25%) was 19 months and 46 months compared with 34 months and 77 months for those with < 400 cPCs respectively (n = 426, 75%) (p < 0.001 for both). The median TTNT and OS for pts based on their R-ISS classification as well as with and without the presence of ≥400 cPCs by MFC was as follows in the following Table. Conclusions: Quantifying ≥400 cPCs/150,000 analyzed events by MFC can potentially upstage the R-ISS classification of a subset of NDMM pts with stage I and II disease and identify those pts with a worse than expected survival outcome.[Table: see text]


2018 ◽  
Vol 63 (1) ◽  
pp. 44-49 ◽  
Author(s):  
Katrin Marquardt ◽  
Peter Ziemke ◽  
Konrad Neumann

Objective: Regarding cytological findings of squamous dysplasia, a comparison was made between a three-tiered classification – low-grade squamous intraepithelial lesion (LSIL), high-grade SIL/cervical intraepithelial neoplasia 2 (HSIL/CIN2), and HSIL/CIN3 – and a two-tiered classification – LSIL and HSIL. The respective risk for CIN2+ and CIN3+ was calculated to make decisions regarding management. Methods: A total of 2,949 women with first-time cytologic findings of squamous dysplasia (LSIL, HSIL/CIN2, or HSIL/CIN3) between January 2013 and June 2016 were enrolled. Subsequent cytological findings and histological diagnoses were evaluated until August 2018. For each category of findings, the risk for CIN2+ and CIN3+ was determined by Kaplan-Meier estimates. The differences in risk between the cytological categories were checked for significance using the log-rank test. Results: For the categories LSIL, HSIL/CIN2, and HSIL/CIN3, the risk for CIN2+ after 12, 24, and 60 months was 3.4, 9.4, and 23.3%; 35.2, 44.8, and 59.8%; and 95.5, 97.8, and 98.9%, respectively. For CIN3+ the risk was 2.0, 5.5, and 13.5%; 28.6, 35.6, and 48.3%; 91.3, 95.6, and 97.9%, respectively. The differences in risk between the categories are highly significant, respectively (p < 0.001). Conclusion: A three-tiered classification of squamous dysplasia such as the Munich Nomenclature III for cytology is suitable for risk-adapted clinical management, especially to avoid overdiagnosis and overtreatment.


Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2141-2141
Author(s):  
Angela Vitrano ◽  
Giuseppina Calvaruso ◽  
Eliana Lai ◽  
Grazia Colletta ◽  
Alessandra Quota ◽  
...  

Abstract Introduction. In the last few decades, the life expectancy of Thalassemia Major (TM) patients has progressively been increasing. The improvement can be due to several factors, including introduction of chelation treatment (Deferoxamine 1965, Deferiprone 1987, Deferasirox 2006), screening of blood for the most common viral agents, aggressive treatment of infection and improved treatment of cardiac complications. However, no comparative survival curves between TM versus Thalassemia Intermedia (TI) have been so far reported. Moreover, no data on life expectancy, after introduction of chelation treatment have been described. Methods. Data coming from several randomized clinical trials, carried ahead by Campus of Hematology Franco and Piera Cutino-A.O.O.R Villa Sofia-V. Cervello, Palermo (Italy), were retrospectively considered for this study. Primary goal of the study was to provide evidence of possible differences in survival curves between TM versus TI. Survival curves in TM versus TI patients were compared using Kaplan-Meier method and the log-rank test before and after the introduction of Deferoxamine (DFO) (1965). Moreover, Cox regression model was even used to explore risk of death between the two diagnoses. Each dead patient was observed from its birth to its death, and each alive patient was observed from its birth to June 30, 2015. Results. Three hundred seventy-nine patients with TM (n=284, dead 40) and TI (n=95, dead 13) entered into the study. Males were 50.7% of this cohort of patients. Among the cohort of dead patients, 15% (6/40) TM and 76.9% (10/13) TI patients were born before introduction of DFO (1965) . The mean age survival was 50.6 (SE 0.9) and 70.6 (SE 1.7) for TM and TI, respectively. Table 1 shows the main causes of death. In TM patients the most common causes of death were heart damage (16 cases, 40%, Tab. 1), followed by cancer (3 cases, 7.5%, Tab. 1), liver cirrhosis (3 cases, 7.5%, Tab. 1) and infections (3 cases, 7.5%, Tab. 1). In TI patients the most common causes of death were cancer (2 cases, 38.5%, Tab. 1), followed by infections (3 cases, 23.1% , Tab. 1), heart damage (2 case, 15.4%, Tab. 1). Kaplan-Meir curves showed statistically significant difference in TM versus TI survival (log-rank test, p- value<0.0001; Figure 1A). Survival was higher for TI subjects (median age was 73.6 years). Cox regression models of TM versus TI suggested that risk of death for TM patients was 6.8 times higher than TI patients (HR 6.8 (3.3), p- value<0.0001). However, the introduction of chelation treatment (DFO, 1965), changed the Kaplan-Meier curves showing that there was not statistically significant difference between TM versus TI patients in life expectancy ( log-rank test, p- value=0.086; Fig. 1B). Conclusion. These results suggest as TM survival, after the introduction of chelation treatment, improved so much that nowadays it is not different in comparison with TI one's. Moreover, the TM risk of death has been decreased from 6.8 to 2.8 (Cox Model HR 2.8 (1.7), p- value=0.099). These findings, if further confirmed, suggest as, in Western countries, our approach for genetic counselling of "at risk couples" for TM should be reconsidered. Table 1. Causes of death in Thalassemia Major and Thalassemia Intermedia patients. Diagnosis Causes of Death TM n (%) TI n (%) Cancer 3 (7,5) 5 (38,5) Heart Damage 16 (40,0) 2 (15,4) Infection 3 (7,5) 3 (23,1) Multi Organ Failure 1 (2,5) 0 (0,0) Stroke 1 (2,5) 0 (0,0) Liver Failure 3 (7,5) 1 (7,7) Not Available 11 (27,5) 1 (7,7) Other complications not related to Thalassemia 2 (5,0) 1 (7,7) Total 13 40 Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Figure 1. Kaplan-Meier Survival curves of Thalassemia Major versus Thalassemia Intermedia patients before and after the introduction of chelation treatment (DFO, 1965). Disclosures Pepe: Chiesi: Speakers Bureau; ApoPharma Inc: Speakers Bureau; Novartis: Speakers Bureau.


2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15522-e15522
Author(s):  
Wei Liang ◽  
Richard Jove ◽  
Bertram E. Yuh ◽  
Kevin Chan ◽  
Timothy G. Wilson ◽  
...  

e15522 Background: In preclinical models, NTPs appear to establish a pre-metastatic niche that fosters the invasion of metastases (Kowanetz et al. PNAS 2010). This observation still requires clinical validation in MIBC. Methods: Benign LN tissue was obtained from patients (pts) who had undergone cystectomy and LN dissection for documented MIBC. Immunohistochemical (IHC) staining for CD15 (a NTP marker) was performed. Interleukin-17 (IL-17) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3), putative mediators of NTP recruitment, were assessed through the same method (Laan et al. J Immunol 1999; Fielding et al. J Immunol 2008). Positively staining cells were counted and averaged over 8 high power fields. Pts were stratified by the median cell count for each biomarker. Analyses of overall survival (OS) were performed using the Kaplan-Meier method and log-rank test. Results: Of 55 pts with MIBC, 19 pts received no neoadjuvant chemotherapy (NAC), while 36 pts had received NAC with either GC (n=17) or MVAC (n=19). CD15 and IL-17 expression was significantly lower in pts with prior NAC (P<0.001 for both), while expression of pSTAT3 was similar in both groups. Furthermore, across the whole cohort, a strong association was seen between expression of CD15 and IL-17 (r=0.73, P<0.001). Amongst patients with no prior NAC, median OS was higher in those pts with low CD15 v high CD15 (158.7 mos v 36.9 mos, P=0.02), and low pSTAT3 v high pSTAT3 (NR v 106.4 mos, P=0.04). Median OS was numerically higher in pts with low IL-17 v high IL-17 (114.5 v 36.9 mos; P=0.14). Patients with both low CD15/IL-17 had a particularly favorable outcome. Amongst pts with prior exposure to NAC, no difference in survival was noted based on CD15, pSTAT3 or IL-17. Conclusions: NTP recruitment to benign LNs (potentially mediated by IL-17) may be prognostic of OS in pts with MIBC who have not received NAC. Bolstered by these findings, the prognostic value of NTP recruitment will be examined prospectively in SWOG 1011, a trial comparing limited v extended LN dissection in pts with MIBC.


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