bluuebunny/crossref_metadata_2025_split huggingface dataset:
Image guidance for post-prostatectomy radiotherapy: Are we missing the mark?
Authors: Kalman Noah S. , Banez Lionel L. , Gerber Leah , Moul Judd W. , Anscher Mitchell Steven , Lee W. Robert , Koontz Bridget F. 
Published: February 2017

56 Background: Image-guided radiation therapy (IGRT) has been widely adopted for both definitive and post-operative prostate radiotherapy. In the postoperative setting, numerous studies of prostate bed motion have recommended tight planning margins (<10mm) if IGRT is used daily. The purpose of this analysis is to determine the effect of IGRT on the efficacy and toxicity of post-operative prostate radiotherapy. Methods: Between 1998 and 2010, 286 patients received radiation therapy after prostatectomy at Duke. Recurrent disease following radiation therapy was defined as PSA >0.2 ng/ml and rising or initiation of salvage ADT. CTCAE v 4.0 and the RTOG/LENT late morbidity scores were used to grade acute and late toxicities. Risk for biochemical failure and late Grade 2+ GI toxicity were compared between IGRT (N = 113) and non-IGRT (N = 173) patients using multivariable adjusted Cox regression controlling for age, treatment technique (3D vs IMRT), radiation dose, androgen suppression, pathologic Gleason Score, margin status, pathologic stage, and pre-radiotherapy PSA level. Results: The median margin size for patients with IGRT was 7mm (IQR 6-10mm) and 15mm (IQR 7-15mm) for those without IGRT (p < 0.001). Median follow up was 21 months (IQR 15-33 mo) for patients with IGRT and 49 months (IQR 30-73 mo) for those without IGRT (p < 0.001). On multivariate analysis, patients treated with IGRT had a greater risk of progression versus non-daily imaging (HR = 2.51, p < 0.001), as did patients who received salvage versus adjuvant radiotherapy (HR = 2.41, p = 0.005). Higher pathologic Gleason Score (HR = 1.96, p = 0.026) and pathologic stage (HR = 1.93, p = 0.003) conferred increased risk of progression, while positive margin status was protective (HR = 0.53, p = 0.002). Age, radiation dose, androgen suppression, and treatment technique did not affect biochemical outcome (p > 0.1). There were no differences in acute or late GI toxicity according to treatment technique or use of IGRT (both p > 0.1). Conclusions: The use of IGRT was associated with increased biochemical recurrence for patients receiving post-operative prostate radiotherapy. For these patients, we recommend using treatment margins of at least 10mm to address subclinical disease and organ motion.
Prior cancer diagnosis in men with nonmetastatic prostate cancer and the risk of prostate cancer specific and all-cause mortality.
Authors: Mirabeau-Beale Kristina , Chen Ming-Hui , D'Amico Anthony Victor 
Published: February 2017

70 Background: We evaluated the impact of a prior diagnosis of cancer on the risk of prostate cancer specific mortality (PCSM) and all cause mortality (ACM) in men with a diagnosis of non-metastatic prostate cancer (PC). Methods: Using the SEER population data registry, 166,104 men (median age: 66 [Interquartile range (IQR): 60 to 73 years]) diagnosed with prostate cancer (PC) between 2004 and 2007 comprised the study cohort. We used a Fine and Grays competing risks and Cox regression to evaluate the impact a prior cancer diagnosis (excluding non-melanoma skin cancer) had on the risk of PCSM and ACM adjusting for PSA level, Gleason score (GS), tumor (T) category, age at and year of diagnosis, race and whether initial treatment received was curative, non-curative or patients underwent active surveillance (AS) or watchful waiting (WW). Prior to the diagnosis of PC, 1,457 malignancies occurred at a median of 4.8 years. Results: After a median follow up of 2.75 years, 12,453 men died: 3,809 (30.6%) from PC. On multivariable analysis, advancing age in years was associated with an increased risk of PCSM as was Gleason score 8 to 10 PC and the use of WW/AS or non-curative therapy (all p values < 0.001). However, men with a prior cancer were significantly older (median age: 72 vs 66 years, p=0.001) and followed longer (median follow up: 3.0 vs 2.75 years, p < 0.001) and were more likely to have high-risk PC (30.1% vs 26.8%, p=0.01) based on the occurrence of Gleason 8 to 10 PC (19.2% vs 15.1%, P < 0.001) and underwent WW or AS more frequently (30.5% vs 22.5%, p<0.001). Despite these findings which would tend toward an increased risk of PCSM in these men, the adjusted risk of PCSM was significantly decreased in these men (Adjusted Hazard Ratio (AHR): 0.66 [95% Confidence Interval (CI): [0.45, 0.97]; p =0.033) while the risk of ACM was increased (AHR: 2.92 [95% CI: 2.64, 3.23]; p < 0.001) suggesting that competing risks and not curative PC treatment may be accounting for the reduction in the risk of PCSM. Conclusions: In men with a malignancy prior to the diagnosis of PC, a careful assessment of life expectancy is needed to decide on whether curative treatment for PC versus WW or AS is appropriate.
Relationship of sipuleucel-T with time to first use of opioid analgesics (TFOA) in patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC) on the IMPACT trial.
Authors: Small Eric Jay , Higano Celestia S. , Kantoff Philip W. , Whitmore James Boyd , Frohlich Mark Walter , Petrylak Daniel Peter 
Published: February 2017

74 Background: Sipuleucel-T (sip-T) is an autologous cellular immunotherapy which was shown to prolong survival in pts with mCRPC in the pivotal IMPACT trial (NCT00065442) (Kantoff PW et al. N Engl J Med 2010;363:411-22). TFOA was a prespecified secondary end point but was subsequently removed as an end point following a protocol amendment to expand enrollment to include minimally symptomatic pts in addition to asymptomatic pts. TFOA data were nevertheless collected in the 512 pts enrolled in the trial. Methods: At baseline, pts were required to have an average pain score <4 on a 10-point visual analog scale and no ongoing opioid analgesic use (OAU). Concomitant medications were collected until confirmed objective disease progression. OAU was identified by medical review of preferred drug names in the coded concomitant medication information on case report forms (CRFs). OAU unrelated to cancer pain (e.g. meperidine used for infusion reactions) was excluded by medical review of CRFs. Pts not reporting OAU were censored at the time of protocol amendment. TFOA was analyzed using a Cox regression model with adjustment for baseline PSA and LDH. Results: 341 sip-T- and 171 placebo-treated patients were evaluated. Median TFOA was 11.9 months (mo) with sip-T vs 8.3 mo for placebo (hazard ratio=0.727; 95% confidence interval 0.536, 0.987; p=0.041). Censoring rate was high (sip-T, 66.9%; placebo, 61.4%). Median follow-up for OAU was 5.2 mo (sip-T, 5.3 mo; placebo, 5.0 mo). Kaplan-Meier estimates of being opioid free at 12 mo were 48.7% for sip-T vs 39.7% for placebo; curve separation began at 6 mo. Significant independent baseline predictors of shorter TFOA were: higher PSA, alkaline phosphatase; younger age; higher number of bone metastases; Gleason score ≥8; ECOG performance status 1; higher weight; and prior primary radiotherapy. Conclusions: Relative to placebo, sip-T delays the TFOA in patients with asymptomatic or minimally symptomatic mCRPC. Clinical trial information: NCT00065442.
Safety profile of poxviral vaccines: NCI experience.
Authors: Kim Joseph W. , Marte Jennifer L. , Bilusic Marijo , Singh Nishith K. , Heery Christopher Ryan , Madan Ravi Amrit , Pazdur Mary , McMahon Sheri , Rauckhorst Myrna , Schlom Jeffrey , Gulley James L. 
Published: February 2017

85 Background: Recombinant poxviruses have been developed as therapeutic cancer vaccines. Here, we report the safety data from NCI clinical trials with poxviral vaccines. Methods: We evaluated all vaccine injections from 215 patients in 8 clinical trials involving poxviral viral vaccines. The Office of Biotechnology Activities, National Cancer Institute (NCI) Institutional Review Board, and NCI Scientific Review Committee approved all of these trials. Vaccines were consisted of recombinant vaccinia and recombinant fowlpox encoded with 3 human costimulatory molecules (TRICOM), and prostate specific antigen (PSA), or carcinoembryonic antigen, and/or mucin-1. Vaccines were administered at doses between 1.2x108 to 2x109 pfu, subcutaneously, in all patients. Twenty-one patients were also vaccinated intra-tumorally. 84 patients also received other concurrent treatment modalities, such as radiation, celecoxib, ipilimumab, samarium-153, or flutamide on 4 of these trials. All 8 clinical trials involved granulocyte-macrophage colony-stimulating factor (GM-CSF) 100mcg, or recombinant fowlpox encoding GM-CSF at 1x 108pfu as an immune adjuvant. Here, we report here the grade 2 or higher adverse events given at least a possible attribution to vaccine. Results: A total of 1,348 poxviral injections were given in 215 patients. No contact transmission, inadvertent inoculation, or any serious adverse events (AEs) related to vaccinia was observed. Below is the summary of proportion of vaccine administrations associated with specific AEs. Conclusions: These data demonstrate a favorable safety profile of the poxviral vaccines at a broad range of doses, routes of administration, in combination with other treatments, and in various tumor types. Clinical trial information: NCT00060528, NCT00096551, NCT00088413, NCT00081848, NCT00113984, NCT00450619, NCT00450463. [Table: see text]
Association of declining PSA values with a lower risk of progression in the Canary Prostate Cancer Active Surveillance Study (PASS).
Authors: Brooks James D. , Brown Elissa C. , Cooperberg Matthew R. , Newcomb Lisa F. , Carroll Peter , Feng Ziding , Gleave Martin Edwin , Lance Raymond , Sanda Martin G. , Thompson Ian Murchie , Wei John Thomas , Nelson Peter , Lin Daniel W. 
Published: February 2017

88 Background: Active Surveillance of men with low risk prostate cancer entails uncertainty for the patient and physician in determining risk of progression. While PSA determinations are frequently measured in men on active surveillance, no study thus far has found PSA velocity (PSAV) or PSA doubling times that identify patients at risk for clinical progression. However, based on observations in PASS, we hypothesized that men with negative PSAV might be at decreased risk for progression. Methods: From 723 PASS participants, we identified 396 who had at least 5 PSA values over 12-24 months after their diagnosis and prior to progression or last follow-up. Of the 396 patients, 56 progressed as defined by increase in Gleason score or increase in tumor involvement of the core biopsies to ≥ 34%, or increase in clinical stage while 340 men had no progression. PSAV is the slope of the log(PSA) values over time. ROC analysis was used with PSAV as the predictor of biopsy/clinical progression. Results: PSAV was mildly associated with clinical/biopsy progression with an AUC of 0.62 (95% CI: 0.54-0.70). Interestingly, by thresholding PSAV at 0, 150 of 396 men had negative a PSAV. Subjects with with a negative PSAV had a much lower rate of progression while on active surveillance. PSAV<0 had a negative predictive value for progression of 0.93 (95% CI: 0.88-0.97). The progression rate for those with negative PSA velocity was 11/150 ≈ 0.07, or 7% and 18% (45/246) for those with positive PSA velocity. Viewed another way, men with PSAV<0 had a 0.4 fold relative risk of progression compared to men with a positive PSAV or were 60% less likely to have clinical/grade progression than those with positive PSA velocity (95% CI: 0.21-0.75). Conclusions: Declining PSAV in men on active surveillance for clinically localized prostate cancer is associated with a lower risk of clinical progression. Clinical trial information: NCT00756665.
Long-term health-related quality of life in patients treated for localized prostate cancer.
Authors: Punnen Sanoj , Cowan Janet E. , Carroll Peter , Cooperberg Matthew R. 
Published: February 2017

93 Background: Few studies have reported long term quality of life after primary treatment for localized prostate cancer. The objective of this study was report 10 year sexual and urinary quality of life data for men undergoing various treatments in the Cancer of the Prostate Strategy and Research Endeavor database. Methods: Men who have been treated for localized prostate cancer and have baseline and follow up quality of life date made up the study cohort. Primary treatment modalities included radical prostatectomy (RP), external beam radiotherapy (EBRT), brachytherapy (BT), cryotherapy (CT), primary androgen deprivation therapy (ADT), and active surveillance/ watchful waiting (AS/WW). Sexual and urinary quality of life were assessed by the validated UCLA Prostate Cancer Index and measured on a scale from 0-100. Mixed model repeated measures analysis was used to assess the association between primary treatment modality and long term urinary and sexual quality of life. Results: 3, 772 men made up the study cohort. Among all men being treated for prostate cancer the mean urinary function score was 92 at baseline, 76 at 1 year, 81 at 5 years and 77 at 10 years. Urinary bother scores were 84 at baseline, 71 at 1 year, 82 at 5 years, and 78 at 10 years. With respect to sexual function the mean score was 49 at baseline, 23 at 1 year, 29 at 5 years, and 24 at 10 years. Finally, the mean sexual bother score was 59 at baseline, 37 at 1 year, 46 at 5 years, and 47 at 10 years. With respect to quality of life by primary treatment modality most treatments showed a similar pattern of decreased scores in the first year followed by an increased in the following two years and a plateau up to the 10 year mark. EBRT and BT showed a longer decline in sexual and urinary function post treatment while RP scores plateau after 3 years. Conclusions: Men undergoing primary treatment for localized prostate cancer experience declines in sexual and urinary function and bother in the first year which improves after 3 years and plateaus up to 10 years.
Prediction of risk for prostate cancer in histopathologically negative biopsies by multigene epigenetic assay.
Authors: Van Neste Leander , Van Criekinge Wim , Thas Olivier , Bigley Joseph , Stewart Grant Duncan , Harrison David James 
Published: February 2017

95 Background: Many men are biopsied for suspicion of prostate cancer (PCa), often based on a serum PSA test, while cancer is missed in up to 30% of the cases due to sampling errors, leading to uncertainty of diagnosis. The diagnostic process is further complicated due to the fear of overtreatment of insignificant PCa. The multi-center MATLOC (Methylation Analysis To Locate Occult Cancer) study confirmed that epigenetic silencing of key genes is a significant predictor of those men with a histologically negative biopsy whose tumor is missed by the biopsy procedure. The epigenetic profile of GSTP1, APC and RASSF1,determined on collected prostatic tissue, resulted in a negative predictive value (NPV) of 90%, identifying a large proportion of men that could forgo repeat biopsy. In current clinical practice, risk factors are intuitively combined to determine the risk that cancer is missed and the need for rebiopsy. Methods: PCa risk factors age, PSA (> 10 ng/mL), DRE (suspicious) and histopathology (HGPIN or atypical cells) were combined with an epigenetic profile to construct a comprehensive metric that improves PCa risk assessment after a negative biopsy. Logistic regression models were fit on a subset of MATLOC with a complete panel of risk factors (n = 391, ncases = 71, prevalence = 18%). These models were subjected to 10-fold cross validation to assess clinical performance. Results: DNA methylation was the strongest predictor (Youden’s J = 0.303) that PCa was missed by biopsy, while PSA was the lowest performing individual marker (J = 0.083). Combinations of risk factors were evaluated, however, only a model including epigenetic profiling and histology of the initial biopsy could improve upon the results of epigenetics alone (J = 0.361). Cross validation resulted in a sensitivity of 74%, a specificity of 63% and a NPV of 91%. Conclusions: Epigenetic profiling is a significant predictor for PCa risk, especially to identify those men who should (not) undergo a repeat biopsy following a negative initial biopsy. An integrated risk management approach that combines epigenetics with other risk factors, most notably histopathology of the cancer-negative initial biopsy, resulted in an improved prediction for the presence of PCa.
Racial differences in survival outcomes among men with localized prostate cancer.
Authors: Lu-Yao Grace L. , Moore Dirk , Lin Yong , Demissie Kitaw , Shih Weichung , Albertsen Peter C. , DiPaola Robert S. , Yao Siu-Long 
Published: February 2017

98 Background: This study addresses whether the recent favorable survival trends observed among contemporary prostate cancer patients can be extended to African American men who have historically suffered excess prostate cancer mortality. Methods: The study cohort consisted of men over age 65, who resided in the SEER catchment area and were diagnosed with T1-T2 prostate cancer (ICD-O-3 code C61.9) during the period 1992-2005. In order to quantify race-specific prostate cancer mortality, separate competing risk models were fit separately for Whites and Blacks. Results: This study includes 35,509 white men and 5,256 black men who received conservative management for localized prostate cancer. The median age of the patients is 76 years at diagnosis and the median follow-up is 106 months. Overall, African Americans have slightly higher adjusted prostate cancer mortality than Whites (hazard ratio [HR] =1.16; 95% confidence interval [C.I.] 1.03 – 1.29). The racial difference was more pronounced in men with moderately differentiated cancer (HR=1.24, 95% CI 1.05 – 1.45), compared to poorly differentiated cancer (HR=1.00, 95% C.I. 0.85 – 1.18). Further analyses by comorbidity status and income level revealed that African Americans and Whites have similar excellent prostate cancer survival if they lived in areas with incomes above the median. Conclusions: African Americans diagnosed in the contemporary PSA era have similarly excellent survival outcomes as their white counterparts if they lived in areas with incomes above the median. Further studies should be conducted to confirm these findings and assess care and health habits that may improve cancer control and outcomes among African Americans.
First results from the phase III ALTTO trial (BIG 2-06; NCCTG [Alliance] N063D) comparing one year of anti-HER2 therapy with lapatinib alone (L), trastuzumab alone (T), their sequence (T→L), or their combination (T+L) in the adjuvant treatment of HER2-positive early breast cancer (EBC).
Authors: Piccart-Gebhart Martine J. , Holmes Andrew Peter , Baselga Jose , De Azambuja Evandro , Dueck Amylou C. , Viale Giuseppe , Zujewski Jo Anne , Goldhirsch Aron , Santillana Sergio , Pritchard Kathleen I. , Wolff Antonio C. , Jackisch Christian , Lang Istvan , Untch Michael , Smith Ian E. , Boyle Frances , Xu Binghe , Gomez Henry Leonidas , Gelber Richard D. , Perez Edith A. 
Published: February 2017

LBA4 Background: Lapatinib (L) is a HER1-HER2 tyrosine kinase inhibitor. The Adjuvant Lapatinib and/or Trastuzumab Treatment Optimisation (ALTTO) Trial is a randomised, phase III trial comparing 3 oral L-containing regimens with T, each given for 1 year. Methods: From June 2007 to July 2011, 8381 patients (pts) were randomised from 946 sites in 44 countries to receive either L+T, T→L, L, or T. Anti-HER2 therapy was initiated after completing all chemotherapy (N=4613), concurrently with a taxane following anthracycline (N=3337), or concurrently with a non-anthracycline, platinum-containing regimen (N=431). The L arm was closed in Aug 2011 for futility and is not presented. The primary endpoint is invasive disease-free survival (DFS). L+T vs. T is tested for superiority and T→L vs. T is tested for non-inferiority at 1.11 margin. P≤0.025 is required for statistical significance. 850 DFS events in the L+T vs. T comparison would provide 80% power to detect a true hazard ratio (HR) of 0.80 with experiment-wide alpha=0.05. The current analysis was planned to occur either after observing these 850 events or at 4.5 yrs median follow up (MFU). Results: Pt and disease characteristics were well balanced. 40% were node-negative and 57% were hormone receptor positive. Only 555 DFS events for the L+T vs. T comparison were observed at 4.5 years MFU. HR for DFS was 0.84 (97.5% CI, 0.70-1.02; P=0.048; 4-yr DFS%=88% vs. 86%) for L+T vs. T and 0.93 (97.5% CI, 0.76-1.13; non-inferiority P=0.044; 4-yr DFS%=87% vs. 86%) for T→L vs. T. Diarrhoea (75% vs. 20%), rash (55% vs. 20%) and hepatobiliary (23% vs. 16%) adverse events were more frequent in L+T vs. T. Primary cardiac endpoints were infrequent (<1%) in all arms. Conclusions: L+T has lower risk of a DFS event compared with T, and T→L appeared non-inferior to T, but neither finding was statistically significant. The first DFS results of dual HER2 blockade in the adjuvant ALTTO at 4.5 years MFU are unexpected considering the effect shown by doubling the pCR rate with L+T vs. T in the NeoALLTO trial. Follow up continues. Clinical trial information: NCT00490139.
Is axillary lymph node dissection necessary after sentinel lymph node biopsy in patients with mastectomy and pathological N1 breast cancer?
Authors: Fu Yun , Chung Debra , Cao Minh-An D. , Apple Sophia , Chang Helena R. 
Published: February 2017

101 Background: Recently, axillary lymph node dissection (ALND) was shown to be unnecessary in patients with lumpectomy and 1-2 positive nodes detected by sentinel lymph node biopsy (SLNB). The aim of this study was to determine whether patients with mastectomy and pathological N1 disease found by SLNB could forego ALND. Methods: 214 patients with primary invasive breast cancer who were treated by mastectomy and lymph node staging surgery (SLNB or ALND) at UCLA were identified between Jan. 2002 and Dec. 2010. Patients were grouped by their first nodal surgery into SLNB (subgroups: observation, radiation and additional ALND with or without radiation) and ALND groups (subgroups: ALND with or without radiation). Results: After a median follow up of 43.6 months, in the SLNB group, the 5-year OS rate was worse in the observation group (71%) when compared to 94% in the additional ALND group and 100% in the radiation group (p=0.031). Systemic recurrence rate in patients with positive SLNs was also significantly higher in the observation group (17.4%) when compared with 7.8% in the additional ALND and no recurrence in the radiation group (p=0.046). Her-2 expression (p=0.006, HR 7.493, 95%CI 1.781~31.520) was found to predict OS. Young age (p=0.024, HR 0.921, 95%CI 0.857~0.989), higher histological grades (p=0.021, HR 5.571, 95%CI 1.295~23.954), and positive Her-2 status (p=0.013, HR 8.916, 95%CI 1.590~49.995) were significant in predicting systemic recurrence in the multivariate analysis with type of nodal surgery and radiation controlled. Compared to the SLNB group, pain (p=0.021) and lymphedema (p=0.043) occurred more frequently in the ALND group. Conclusions: Radiation was as effective as complete ALND in patients with mastectomy and N1 disease detected by SLNB for OS and relapse free survival rates, yet radiation after SLNB had fewer side effects than ALND. SLNB followed by radiation could replace ALND in patients with mastectomy and pathological N1 breast cancer identified by SLNB.