Loss of p16 Expression Is of Prognostic Significance in Locally Advanced Prostate Cancer: An Analysis From the Radiation Therapy Oncology Group Protocol 86–10

2003 ◽  
Vol 21 (17) ◽  
pp. 3328-3334 ◽  
Author(s):  
A. Chakravarti ◽  
K. Heydon ◽  
C.L. Wu ◽  
E. Hammond ◽  
A. Pollack ◽  
...  

Purpose: The retinoblastoma (RB) cell cycle regulatory pathway is known to be deregulated in virtually all known human tumors. The protein product of the RB gene, pRB, and its upstream regulator, p16, are among the most commonly affected members of this pathway. We investigated the prognostic significance of both pRB and p16 expression in locally advanced prostate cancers, from patients treated on the Radiation Therapy Oncology Group (RTOG) protocol 86–10. Materials and Methods: Sixty-seven cases from RTOG 86–10 had immunohistochemically stained slides, judged interpretable for both p16 and pRB, available for analysis. Median follow-up was 8.9 years (range, 6.0 to 11.8 years) for surviving patients. Staining for each marker was then correlated with overall survival, local progression, distant metastasis, and disease-specific survival. Results: Loss of p16 expression, as defined by expression was significantly associated with reduced overall survival (P = .039), disease-specific survival (P = .006), and higher risk of local progression (P = .0007) and distant metastasis (P = .026) in the univariate analysis. In the multivariate analysis, loss of p16 was significantly associated with reduced disease-specific survival (P = .0078) and increased risk of local failure (P = .0035) and distant metastasis (P = .026). A borderline association with reduced overall survival (P = .07) was also evident. Loss of pRB was associated with improved disease-specific survival on univariate (P = .028) and multivariate analysis (P = .043), but carried no other significant outcome associations. Conclusion: Loss of p16 is significantly associated with adverse clinical outcome in cases of locally advanced prostate cancer.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. CRA4504-CRA4504 ◽  
Author(s):  
P. R. Warde ◽  
M. D. Mason ◽  
M. R. Sydes ◽  
M. K. Gospodarowicz ◽  
G. P. Swanson ◽  
...  

CRA4504 Background: The impact of radiotherapy on overall survival (OS) in men with locally advanced CaP is unclear. The SPCG-7 trial recently showed a benefit to RT for CaP specific mortality. Our primary objective was to assess the effect of RT on OS when added to lifelong ADT in men with locally advanced CaP. Methods: Patients with T3/T4 (1057) or T2, PSA > 40 μ g/l (119) or T2 PSA > 20 μ g/l and Gleason ≥ 8 (25) and N0 /NX, M0 prostate adenocarcinoma were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) with or without RT (65-69 Gy to prostate ± seminal vesicles with or without 45Gy to pelvic nodes). The primary endpoint was OS and secondary endpoints included disease specific survival (DSS), time to disease progression and quality of life. Results: 1205 patients were randomized from 1995 to 2005, 602 to ADT and 603 to ADT+RT (well balanced with respect to baseline characteristics). A protocol specified second interim analysis on OS was performed in Aug 2009 (data cut-off Dec 31 2008). The DSMC recommended release of the results to the Trial Committee for publication. The median follow-up is 6.0 years and 320 patients have died (175 ADT and 145 ADT+RT). 10% of patients had no follow-up data beyond 2006. The addition of RT to ADT significantly reduced the risk of death (hazard ratio [HR] 0.77, 95% CI 0.61-0.98, p=0.033). 140 patients died of disease and/or treatment (89 on ADT and 51 on ADT+RT) The disease specific survival HR was 0.57 (95% CI 0.41-0.81, p=0.001) favoring ADT+RT. The 10 year cumulative disease specific death rates were estimated at 15% with ADT+ RT and 23% with ADT alone. Grade ≥2 late GI toxicity rates were similar in both arms (proctitis, 1.3% ADT alone, 1.8% ADT+RT). Conclusions: The trial results indicate a substantial overall survival and disease specific survival benefit for the combined modality approach (ADT+RT) in the management of patients with locally advanced prostate cancer with no significant increase in late treatment toxicity. In view of this data combined modality therapy (ADT+RT) should be the standard treatment approach for these patients. Supported by NCI-US Grant #5U10CA077202-12, CCSRI Grant #15469. No significant financial relationships to disclose.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4509-4509 ◽  
Author(s):  
Malcolm David Mason ◽  
Wendy Parulekar ◽  
Matthew Robert Sydes ◽  
Mahesh Parmar ◽  
John Anderson ◽  
...  

4509 Background: Data from the SPCG-7 study and interim analysis of this trial have demonstrated an overall survival (OS) benefit for RT when added to ADT. We present the protocol specified final analysis of PR3/PR07. Methods: Patients with locally advanced (T3/T4, N0/NX, n=1057) or organ-confined prostate cancer (T2,N0/NX, with either PSA > 40 μg/l or PSA > 20 μg/l and Gleason > 8, n=144) were randomized to lifelong ADT (bilateral orchiectomy or LHRH agonist) or ADT + RT (65-69 Gy to prostate + seminal vesicles with or without 45Gy to pelvic nodes). The primary outcome measure was OS; secondary outcomes included disease-specific survival (DSS), time to disease progression and quality of life. Final analysis was planned after 421 deaths. Results: 1,205 patients were randomized from 1995-2005, 602 to ADT alone and 603 to ADT+RT (well balanced with respect to baseline characteristics). The median follow-up is 8.0 years and 465 patients have died (260 ADT, 205 ADT+RT). Adding RT to ADT significantly reduced the risk of death (Hazard Ratio 0.70, 95% CI 0.57-0.85, p=0.001). 199 patients died of disease and/or treatment (134 on ADT alone and 65 on ADT+RT). Competing risk analysis demonstrated that patients on the ADT alone arm had a significantly higher chance of dying of disease related causes than those treated with ADT+RT (10 year cumulative disease specific death rates 15% with ADT+ RT, 26% with ADT alone, p<0.0001). The addition of RT to ADT had a small detrimental effect on late gastrointestinal toxicity and health-related quality-of-life (> grade II proctitis, 0.3% ADT alone, 1.0% ADT+RT; mean change EORTC Rectal symptoms -0.3 ADT vs 1.7 ADT + RT, p=0.54). Conclusions: Mature data indicate a sustained and substantial overall survival and disease specific survival benefit for ADT+RT in the management of patients with locally advanced prostate cancer with minimal increase in late treatment toxicity. The benefits of combined modality treatment should be discussed with all patients. Supported by NCI-US Grant CA077202, CCSRI Grants #14469 and # 015469, UK Medical Research Council Grant G9805643, UK National Cancer Research Network.


2000 ◽  
Vol 18 (14) ◽  
pp. 2740-2746 ◽  
Author(s):  
Richard Valicenti ◽  
Jiandong Lu ◽  
Miljenko Pilepich ◽  
Sucha Asbell ◽  
David Grignon

PURPOSE: We evaluated the effect of external-beam radiation therapy on disease-specific survival (death from causes related to prostate cancer) and overall survival in men with clinically localized prostate cancer. METHODS: From 1975 to 1992, 1,465 men with clinically localized prostate cancer received radiation therapy on four Radiation Therapy Oncology Group phase III randomized trials and were pooled for this analysis. No one received androgen-deprivation therapy with his initial treatment. All original histology had central pathologic review for grading using the Gleason classification system. Total delivered radiation dose ranged from 60 to 78 Gy (median, 68.4 Gy). The median follow-up time was 8 years. RESULTS: A Cox regression model revealed that Gleason score was an independent predictor of disease-specific survival and overall survival. The 10-year disease-specific survival rates by Gleason score were as follows: score of 2 through 5, 85%; score of 6, 79%; score of 7, 62%; and score of 8 through 10, 43%. Stratifying outcome by this important prognostic factor revealed that higher radiation dose was a significant predictor for improved disease-specific survival and overall survival only for those patients whose cancers had Gleason scores of 8 through 10 (P < .05). After adjusting for clinical T stage, nodal status, and age, treating with a higher radiation dose was associated with a 29% lower relative risk of death from prostate cancer and 27% reduced mortality rate (P < .05). CONCLUSION: These data demonstrate that higher-dose radiation therapy can significantly reduce the risk of dying from prostate cancer in men with clinically localized disease. This survival benefit is restricted to men with poorly differentiated cancers.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7529-7529
Author(s):  
S. N. Waqar ◽  
F. Gao ◽  
R. Govindan ◽  
D. Morgensztern

7529 Background: Although tumor size is a known predictor of stage I and II non-small cell lung cancer (NSCLC) treated with surgery or radiotherapy, there is limited information regarding its prognostic significance in patients with mediastinal lymph node involvement. Methods: The Surveillance Epidemiology and End Results (SEER) registry was queried for patients with unresected NSCLC stage III, without malignant pleural effusion, aged 21 or older, and diagnosed between 1998 and 2003. Tumor size was defined as S1 (0.1–3 cm), S2 (3.1–5 cm), S3 (5.1–7 cm) and S4 (7.1–20 cm). Demographic variables included age, gender, race and histology. The Kaplan-Meier method was used to estimate the overall survival (OS) and disease-specific survival (DSS), and the Cox proportional hazard model to evaluate whether tumor size remained an independent risk factor after adjusting for stage and other demographic variables. Results: A total of 12,205 patients met the eligibility criteria. Median age at diagnosis was 70 years and most patients were male (58.8%) and white (81.3%). Tumor size was a statistically significant predictor for both overall survival (p<0.0001) and disease-specific survival (p<0.0001) on multivariate analysis. Selected groups of patients with smaller stage IIIB disease had better OS compared to patients with stage IIIA, including; IIIBS1 vs. IIIAS3 (p=0.0005) or IIIA S4 (p<0.0001) and IIIBS2 vs. IIIAS4 (p=0.0001). Conclusions: Tumor size is an independent predictor for OS and DSS in patients with unresected stage III NSCLC and should be considered in the stratification of patients treated in this setting. [Table: see text] No significant financial relationships to disclose.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yanhong Li ◽  
Mei Wang ◽  
Xueping Zhu ◽  
Xu Cao ◽  
Yi Wu ◽  
...  

Background. The expression of the cancerous inhibitor protein phosphatase 2A (CIP2A) appears to be predictive of the prognosis of various solid tumors. However, the association between this protein and the risk of esophagogastric junction adenocarcinoma (EGJA) remains unclear. We investigated CIP2A expression and its clinical significance in EGJA and conducted a meta-analysis to explore the relationship between CIP2A and the prognosis of patients with solid tumors. Methods. Immunohistochemistry (IHC) was performed to detect the expression of CIP2A in EGJA. Kaplan-Meier estimation, Cox analysis, and ROC curves were performed to analyze the survival of patients and the prognostic factors. In the meta-analysis, we searched relevant publications in several widely used databases and used 15 studies (2348 patients). Results. IHC demonstrated that CIP2A was elevated in EGJA and correlated with poor survival as an independent indicator. It could forecast the survival more precisely when combined with the grade, which is another independent prognosis marker of EGJA. Meta-analysis demonstrated that the associations between the expression of CIP2A and the prognosis were detected for overall survival (HR=1.98, 95%CI=1.69‐2.32), disease-specific survival (HR=1.72, 95%CI=1.50‐1.97), and time to tumor progression (pooled HR=1.95, 95%CI=1.56‐2.43). Conclusion. High expression of CIP2A was a poor indicator of the prognosis of EGJA, and CIP2A may be a new biomarker for the diagnosis and treatment of EGJA. The meta-analysis suggested that CIP2A expression can be a predictive marker of overall survival, disease-specific survival, and time to tumor progression in patients with solid tumors.


2007 ◽  
Vol 25 (21) ◽  
pp. 3082-3089 ◽  
Author(s):  
Arnab Chakravarti ◽  
Michelle DeSilvio ◽  
Min Zhang ◽  
David Grignon ◽  
Seth Rosenthal ◽  
...  

Purpose Deregulation of the retinoblastoma (RB) pathway is commonly found in virtually all known human tumors. p16, the upstream regulator of RB, is among the most commonly affected member of this pathway. In the present study, we examined the prognostic value of p16 expression in men with locally advanced prostate cancer who were enrolled on Radiation Therapy Oncology Group protocol 9202. Patients and Methods RTOG 9202 was a phase III randomized study comparing long-term (LT) versus short-term (ST) androgen-deprivation therapy (AD). Of the 1,514 eligible cases, 612 patients had adequate tumor material for p16 analysis. Expression levels of p16 were determined by immunohistochemistry (IHC). IHC staining was scored quantitatively using an image analysis system. Results On multivariate analysis, intact p16 expression was significantly associated with decreased rate of distant metastases (P = .0332) when both STAD and LTAD treatment arms were considered together. For patients with intact (high levels of immunostaining) p16 (mean p16 index > 81.3%), LTAD plus radiotherapy (RT) significantly improved prostate cancer survival (PCS) compared with STAD plus RT (P = .0008) and reduced the frequency of distant metastasis (P = .0069) compared with STAD plus RT. In contrast, for patients with tumors demonstrating p16 loss (low levels of immunostaining, mean p16 index ≤ 81.3%), LTAD plus RT significantly improved biochemical no evidence of disease survival over STAD (P < .0001) primarily by decreasing the frequency of local progression (P = .02), as opposed to distant metastasis, which was the case in the high-p16 cohort. Conclusion Low levels of p16 on image analysis appear to be associated with a significantly higher risk of distant metastases among all study patients. p16 expression levels also appear to identify patients with locally advanced prostate cancer with distinct patterns of failure after LTAD.


Author(s):  
Haider A. Mejbel ◽  
Carlos A. Torres-Cabala ◽  
Denái R. Milton ◽  
Doina Ivan ◽  
Priyadharsini Nagarajan ◽  
...  

Context.— Acral lentiginous melanoma is a rare and aggressive type of cutaneous melanoma that arises on the acral skin and the nail unit. The prognostic significance of subungual anatomic site in acral lentiginous melanoma is not established. Objective.— To assess the impact of subungual anatomic site on overall survival and disease-specific survival in acral lentiginous melanoma. Design.— Retrospective cohort analysis. Clinicopathologic characteristics of 627 primary acral lentiginous melanomas (45 [7%] subungual and 582 [93%] nonsubungual) were summarized, and the impact of these characteristics on overall survival and disease-specific survival was determined using univariate and multivariable analyses. Results.— No significant differences in clinicopathologic features were identified between the subungual and nonsubungual acral lentiginous melanomas. The 1-, 5-, and 10-year overall survival rates were 81%, 40%, and 28%, respectively, for subungual acral lentiginous melanoma and 94%, 59%, and 38%, respectively, for nonsubungual acral lentiginous melanoma (P = .04); risk of death was significantly higher for subungual tumors (hazard ratio [95% confidence interval] = 1.59 [1.02–2.50]; P = .04). The 1-, 5-, and 10-year disease-specific survival rates were 94%, 56%, and 48%, respectively, for subungual acral lentiginous melanoma versus 96%, 69%, and 55%, respectively, for nonsubungual acral lentiginous melanoma (P = .18). By multivariable analysis, independent poor prognostic factors included older age and ulceration for overall survival and greater Breslow thickness and sentinel lymph node positivity for overall survival and disease-specific survival. Subungual anatomic site was not an independent prognostic factor for overall or disease-specific survival. Conclusions.— Subungual anatomic site is not an independent prognostic factor for acral lentiginous melanoma.


2020 ◽  
Author(s):  
Zhao Yang Wang ◽  
Yuanzhu Jiang ◽  
Wen Xiao ◽  
Xianbiao Xue ◽  
Xiangwei Zhang ◽  
...  

Abstract Background: In clinical work, it is increasingly finding that even for patients with the same TNM stage of esophageal cancer (EC), the prognosis of different patients is still very different. Tumor length has been analyzed as a possible independent prognostic factor in many studies, but no unanimous conclusion has been reached. Therefore, this review is expected to use meta-analysis to evaluate the association between tumor length and prognostic significance in EC patients.Methods: A systematic search for relevant articles was performed in the PubMed, Web of Science, and Embase. Hazard ratio and 95% confidence intervals (CIs) will be used as effective measures to estimate the correlation between tumor length and prognostic significance including overall survival, disease-free survival, progression-free survival, disease-specific survival, and cancer-specific survival. We will use the software STATA 15.0 to perform the meta-analysis to calculate the data synthesis. Results: Finally, 41 articles with 28, 973 patients were included in our study. Comprehensive statistical results showed that long tumor is an independent prognostic parameter associated with poor overall survival (OS) (HR=1.30; 95%CI: 1.21-1.40, p<.001) and disease-free survival (DFS) (HR=1.38; 95% CI:1.18-1.61, p<.001) in EC patients. Subgroup analyses also suggested a significant correlation between long tumor and poor OS. Sensitivity analysis and publication bias evaluation confirmed the reliability and stability of these results. Similar results can be obtained in analyses of progress-free survival (PFS), disease-specific survival (DSS), and cancer-specific survival (CSS). Conclusion: The results of this meta-analysis showed that the long tumor was related to the poor OS, DFS, PFS, DSS and CSS in EC patients. It was suggested that tumor length might be an important predictor of prognosis in EC patients,and it can be used as an independent staging index. Further well-designed and large-scale prospective clinical studies are needed to confirm these findings.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hiroaki Saito ◽  
Shota Shimizu ◽  
Yuji Shishido ◽  
Kozo Miyatani ◽  
Tomoyuki Matsunaga ◽  
...  

Abstract Background Platelet distribution width (PDW) and red cell distribution width (RDW) are readily obtainable data, and are reportedly useful as prognostic indicators in some cancers. However, their prognostic significance is unclear in gastric cancer (GC). Methods We enrolled 445 patients with histopathological diagnoses of gastric adenocarcinoma who had undergone curative surgeries. Results According to the optimal cut-off value of PDW and RDW by receiver operating characteristic (ROC) analysis, we divided patients into PDWHigh (≥ 16.75%), PDWLow (< 16.75%), RDWHigh (≥ 14.25%), and RDWLow (< 14.25%) subgroups. Overall survival (OS) was significantly worse in patients with PDWHigh than in those with PDWLow (P = 0.0015), as was disease specific survival (P = 0.043). OS was also significantly worse in patients with RDWHigh than in those with RDWLow (P <  0.0001), as was disease specific survival (P = 0.0002). Multivariate analysis for OS revealed that both PDW and RDW were independent prognostic indicators. Patients were then given PDW-RDW score by adding points for their different subgroups (1 point each for PDWHigh and RDWHigh; 0 points for PDWLow and RDWLow). OS significantly differed by PDW-RDW score (P <  0.0001), as did disease specific survival (P = 0.0005). In multivariate analysis for OS, PDW-RDW score was found to be an independent prognostic indicator. Conclusions The prognosis of GC patients can be precisely predictable by using both PDW and RDW.


2021 ◽  
Author(s):  
Mu-Hung Tsai ◽  
Shang-Yin Wu ◽  
Tsung Yu ◽  
Sen-Tien Tsai ◽  
Yuan-Hua Wu

Abstract Background and purpose Concurrent chemoradiotherapy is the established treatment for locally advanced nasopharyngeal carcinoma (NPC). However, there is no evidence supporting routine adjuvant chemotherapy. We aimed to demonstrate the effect of adjuvant chemotherapy on survival and distant metastasis in high-risk N3 NPC patients. Materials and methods We linked the Taiwan Cancer Registry and Cause of Death database to obtain data. Clinical N3 NPC patients were divided as those receiving definitive concurrent chemoradiotherapy (CCRT) with adjuvant 5-fluorouracil and platinum (PF) chemotherapy and those receiving no chemotherapy after CCRT. Patients receiving neoadjuvant chemotherapy were excluded. We compared overall survival, disease-free survival, local control, and distant metastasis in both groups using Cox proportional hazards regression analysis. Results We included 431 patients (152 and 279 patients in the adjuvant PF and observation groups, respectively). Median follow-up was 4.3 years. The 5-year overall survival were 69.1% and 57.4% in the adjuvant PF chemotherapy and observation groups, respectively (p = 0.02). Adjuvant PF chemotherapy was associated with a lower risk of death (hazard ratio [HR] = 0.61, 95% confidence interval [CI]: 0.43–0.84; p = 0.003), even after adjusting for baseline prognostic factors (HR = 0.61, 95% CI: 0.43–0.86; p = 0.005). Distant metastasis-free survival at 12 months was higher in the adjuvant PF chemotherapy group than in the observation group (98% vs 84.8%; p < 0.001). After adjusting for baseline prognostic factors, adjuvant PF chemotherapy was associated with freedom from distant metastasis (HR = 0.11, 95% CI: 0.02–0.46; p = 0.003). Conclusion Prospective evaluation of adjuvant PF chemotherapy in N3 NPC patients treated with definitive CCRT is warranted because adjuvant PF chemotherapy was associated with improved overall survival and decreased risk of distant metastasis.


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