bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic indicators of aggressive disease in patients with locally advanced or metastatic prostate cancer: A focus on neutrophil to lymphocyte and platelet to lymphocyte ratios.
Authors: Dabaja A. , Menon M. , Agarwal P. 
Published: February 2017

62 Background: Prostate specific antigen (PSA) and Gleason Score (GS) are helpful in predicting aggressive disease. Recently, the neutrophil:lymphocyte ratio (NLR) and platlet:lymphocyte ratio (PLR) were identified as prognostic indicators in gastric cancer which has an inflammatory pathogenesis. We hypothesized that these indicators may be prognostic in prostate cancer which is also postulated to have an inflammatory mechanism of carcinogenesis. Our goal was to assess if NLR and PLR is predictive of aggressive prostate cancer, which will be measured by metastasis and overall survival in patients on hormonal therapy as treatment. Methods: We performed a retrospective analysis of 246 patients that were being treated with hormone therapy for either locally advanced or metastatic disease, or who were not surgical candidates or refused surgery. A logistic regression model was used to analyze various prognostic factors including total GS, pre-biopsy PSA, perineural invasion, % of core biopsies positive, NLR, and PLR. Endpoints studied were overall survival and metastasis. Results: The logistic regression showed only pre biopsy PSA as a predictor of metastasis (n=82). The increased risk when measured continuously was 0.6% increase in odds ratio (p<0.015). When PSA was measured categorically the % biopsy cores positive were predictive of increased risk of metastatic disease with a 2.9% increase in odds ratio (p<0.002). The % biopsy cores positive were predictive of a 3.7% increased odds ratio in cancer-specific mortality (p<0.002). These results were controlled for age, which gave a 7% increase in odds ratio of overall survival (p<0.049). Conclusions: Despite the thought that prostate cancer has an inflammatory pathogenesis, no correlation was found between N:L and P:L ratios and overall survival or bone metastasis in patients on hormone therapy for locally advanced disease. There was a negative correlation between increased % positive biopsy cores a decreased risk of survival. Further investigation is necessary to investigate the role of NLR and PLR as prognostic indicators in organ confined prostate cancer. No significant financial relationships to disclose.
Long-term (potential 10-year follow-up) toxicity after treatment for prostate cancer with either external beam radiation therapy, interstitial brachytherapy, or radical prostatectomy.
Authors: Hunter G. K. , Reddy C. A. , Angermeier K. , Ulchaker J. , Stephans K. L. , Tendulkar R. D. , Zippe C. , Kupelian P. , Klein E. A. , Ciezki J. P. 
Published: February 2017

65 Background: To examine gastrointestinal (GI) and genitourinary (GU) toxicity profiles of patients treated in 1999 with external beam radiotherapy (RT), prostate interstitial brachytherapy (PI) or radical prostatectomy (RP). Methods: The records of 483 patients treated in 1999 were retrospectively reviewed to evaluate toxicity profiles, with 24% of the patients treated with PI, 40% with RP, and 36% with RT. Late GI and GU morbidity profiles were specifically examined and both were graded according to the RTOG acute and late morbidity scoring criteria. Other factors examined were patient age, BMI, smoking history, and medical comorbidities including presence of diabetes mellitus (DM), peripheral vascular disease, and connective tissue disease. Due to the low event rate for late GU and GI toxicities, a competing risk regression (CRR) analysis was done with death as the competing event. Results: See Table. Median follow-up time was 8.6 years (range 0.2-11.5). On CRR univariate analysis the presence of DM was associated with GU toxicity grade ≥2 (p=0.043, HR 2.35, 95% CI=1.03-5.39). DM remained significant on multivariate analysis (p=0.034, HR 2.44, 95% CI= 1.07-5.59). Since there were no events in the RP group, only the PI and RT patients were included in the CRR analysis for late GI toxicity Grade <=2. On univariate analysis, RT and DM were significantly associated with late GI toxicity. On multivariable analysis, both variables remained significant (RT: p=0.038, HR=4.71, 95%CI=1.09-20.3; DM: p=0.008, HR=3.81, 95%CI=1.42-10.2). Conclusions: Late effects occur with all three treatment modalities. The presence of DM at the time of treatment was significantly associated with worse late GI and GU toxicity. RT was significantly associated with worse late GI toxicity compared to PI and RP. [Table: see text] No significant financial relationships to disclose.
Long-term QOL outcome after proton beam monotherapy for localized prostate cancer.
Authors: Coen J. , Paly J. J. , Weyman E. A. , Rodrigues A. , Shipley W. U. , Zietman A. L. , Efstathiou J. A. , Talcott J. A. 
Published: February 2017

68 Background: High-dose conformal proton radiation for localized prostate cancer results in favorable clinical outcomes and low toxicity rates. Here, we report long-term quality of life (QOL) outcome for men treated with conformal protons. Methods: Serial QOL questionnaires were administered to men who received proton radiation. Long-term questionnaires (minimum 2 years) were completed by 72 patients. Men were stratified into functional groups from their baseline questionnaires (normal, intermediate or poor function) for each symptom domain. Symptom scores were calculated at baseline and long-term follow-up and expressed as mean values. QOL changes were assessed overall and within functional groups in a paired fashion using the Student's t-test. Results: The median age at treatment and follow-up were 66 years and 44 months, respectively. The median dose was 82 GyE (range 74-82 GyE). For all 72 patients, there were increased scores for incontinence (ID) (3.2 baseline vs. 9.9 long-term, p=<0.001), obstructive/irritative voiding (OID; 20 vs. 24, p=0.028), bowel (BD; 4.4 vs. 8.0, p=0.001) and sexual dysfunction (SD; 25 vs. 48, p<0.001). When stratified by functional category, more specific estimates were possible. For ID, only normal function was associated with a significant increased score (0 vs. 8.4 at baseline and long-term, p=<0.001); for OID, only the group with normal baseline function showed a significant increased score (12 vs. 17, p=0.01); similarly for BD, only men with normal function had a significant increased score (0 vs. 5.4, p<0.001). For SD, the score increased in men with normal (1.4 vs. 30, p<0.001) and intermediate function (17 vs. 46, p<0.001). Conclusions: Patient reported outcomes are sensitive indicators of treatment related sequelae and here quantitate, for the first time, the long-term consequences of proton monotherapy for prostate cancer. Analysis by baseline functional category is a useful means of predicting long-term QOL scores for an individual patient. High-dose proton radiation was associated with small increases in bowel dysfunction, obstructive/irritative voiding dysfunction and incontinence. With long term follow-up, sexual dysfunction increased more than any other symptom domain. No significant financial relationships to disclose.
Prostate cancer incidence and disease-specific survival in men participating in the ERSPC with an initial PSA less than 3.0 ng/mL.
Authors: Bul M. , van Leeuwen P. J. , Zhu X. , Schröder F. H. , Roobol M. J. 
Published: February 2017

7 Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) applies a prostate- specific antigen (PSA) cut-off >3.0 ng/mL as an indication for biopsy. We analyzed the incidence and disease-specific mortality for prostate cancer (PC) within ERSPC Rotterdam for men with an initial PSA <3.0 ng/ml in a 15-year follow-up period. Methods: From 1993-1999, a total of 42,376 men identified from population registries in the Rotterdam region (55-74 yrs) were randomized to a screening or control arm. During the first screening round 19,950 men were screened, with biopsies being initially recommended in case of abnormal DRE or PSA >4.0 ng/mL. From 1997 on, solely PSA >3.0 ng/mL was used. The screening interval was 4 yrs. A total of 15,758 men (79%) had an initial PSA <3.0 ng/mL. Follow-up was complete until January 2009. Results: From 1993-2008, 915 PC cases were diagnosed in 15,758 men (5.8%, median age 62.3 yrs) with an initial PSA <3.0 ng/mL (733 screen detected and 182 interval detected). Median follow-up was 11 yrs. PC incidence increased significantly with higher initial PSA levels (Table). Aggressive PC (clinical stage >T2c, Gleason score >8, PSA >20 ng/mL, positive lymph nodes or metastases at diagnosis) was detected in 65/733 screen detected PC (8.9%) and 102/182 interval detected PC (56.0%). PC death occurred in 23 cases (5 screen detected and 18 interval detected) in the total population (0.15%), with increasing risk in men with higher initial PSA values. Conclusions: The risk of (aggressive) PC and PC mortality in a screening population with initial PSA <3.0 ng/mL increases significantly with higher PSA levels. The risk of dying of PC is minor in men with initial PSA <1.0 ng/mL. Interval detected PC is more aggressive and has a substantial influence on PC specific mortality. [Table: see text] [Table: see text]
Is radiation therapy superior to conservative management in men with localized prostate cancer?
Authors: Lu-Yao G. L. , Kim S. , Moore D. , Shih W. , Lin Y. , DiPaola R. S. , Zietman A. L. , Yao S. 
Published: February 2017

73 Background: Radiation therapy is commonly employed for localized prostate cancer; however, there is little data regarding the comparative effectiveness of radiation therapy (RAD) vs. conservative management (CM). Methods: We performed a population-based cohort study, using Medicare claims data linked to the Surveillance, Epidemiology, and End Results data, to evaluate outcomes in 42,039 men aged 65-85 years treated with either primary RAD or CM for T1-T2 prostate cancer diagnosed in 1992-2005. To overcome potential biases associated with unmeasured confounding variables, we used instrumental variable analysis (IVA), a pseudo-randomization technique that captures the randomness associated with geographic variations in the use of RAD, to control for overt and hidden confounders. Results: The majority of patients (57%) had low-risk disease (Gleason score ≤7, PSA <10, and T stage ≤T2a), and RAD was commonly used (60%) with considerable geographic variations. With median age 74 years and median follow-up 119 months, higher RAD use was not associated with improved survival in low-risk patients (10-year disease-specific survival differed by −0.9%, 94.9% vs. 95.8% in the highest and lowest tertile RAD use areas respectively; 95% C.I. −.1 to 0.6%). Among high-risk patients (Gleason score >7 or PSA >20), highest tertile RAD areas showed a borderline improved (2.7%) 10-year disease-survival (83.9% vs. 81.2% in the highest and lowest tertile radiation use areas; 95% C.I. −1.1% to 7.0%). The results in the moderate-risk group were between that of the low- and high-risk group. Primary RAD did not reduce future ADT use (odds ratios 0.95 for low-risk, 1.02 for moderate-risk, and 1.07 for high-risk with corresponding P values of 0.50, 0.86, and 0.51, respectively). Conclusions: In patients aged over 65 years old with low-risk prostate cancer, primary RAD is unlikely to improve 10-year disease-specific survival or prevent future ADT use. Weighing the potential risks and benefits of radiation therapy is critical for decision making. No significant financial relationships to disclose.
Efficacy and rectal toxicity of hypofractionated radiation therapy with daily image guidance.
Authors: McDonald A. M. , Dobelbower M. C. , Kim R. Y. , Jacob R. , Bishop J. , Fiveash J. B. 
Published: February 2017

85 Background: To assess the biochemical control rates and long-term rectal side effect profile of hypofractionated image guided radiation therapy for prostate cancer. We hypothesize that daily CT-based image guidance will allow a higher dose per fraction to be safely administered, shortening the overall treatment time from 8 weeks to 4-5.5 weeks. Methods: 160 patients were treated with image guided radiation therapy with or without adjuvant hormonal ablation between 2005 and 2009 for patients <= T3a N0 M0. Patients were classified into risk groups with 51 patients defined as low risk, 67 as intermediate risk, and 43 as high risk. Mean age was 70.2 years. All patients were treated with 60/67.6/70/70.2 Gy to the prostate divided into 20/26/28/27 fractions. 57% of patients received hormone therapy. Daily CT or fiducial-based image guidance was performed prior to each fraction. The median follow up was 34 months. Biochemical control was defined by the Phoenix definition. Rectal toxicity was graded by the CTCAE 4.0 scale. In general patients with rectal bleeding more than once per week were started on rectal steroids. Results: 12/160 (7.5%) of patients had late grade 2 or worse rectal toxicity after radiation treatment. The Kaplan-Meier estimate for grade 2 rectal toxicity at 2 years was 6.9%. The crude rate of biochemical no evidence of disease was 96.3%. Kaplan Meier estimates for biochemical no evidence of disease at 3 and 5 years are 0.98/0.84, 0.97/0.97, and 1.0/0.67 for low, medium, and high-risk patients respectively. Log-rank analysis showed no statistically significant difference among the dosing regimens for toxicity-free survival (p=0.24). Conclusions: With daily image guidance hypofractionated radiation therapy is clinically safe with moderate late rectal toxicity. Early follow-up suggests high efficacy. Ongoing and future randomized trials such as RTOG 0415 will be required to confirm these findings. No significant financial relationships to disclose.
Two-year PSA outcomes after cesium prostate brachytherapy.
Authors: Smith R. , Jacobs B. L. , Beriwal S. , Benoit R. M. 
Published: February 2017

92 Background: Given the long natural history of prostate cancer, long term follow up is needed to definitively know the efficacy of a new treatment, in this case 131Cs brachytherapy. However, it is also important to report on short term outcomes to ensure that this treatment is on course to provide equivalent outcomes as compared to existing treatment options. This reports two year PSA outcomes in men undergoing prostate brachytherapy with cesium 131 at a single institution. Methods: All patients who underwent prostate brachytherapy with 131Cs and had at least 24 months of follow up were included in this study. Results are reported for the total cohort and stratified by risk group as well as treatment received (monotherapy, combination therapy, or trimodal therapy). The Phoenix definition was used to define biochemical disease free survival (bDFS). Outcomes were analyzed using descriptive statistics. Results: 115 patients underwent prostate brachytherapy with 131Cs and had at least 24 months of follow up. Fifty two (45.2%) patients were classified as low risk, 52 (45.2%) were intermediate risk, and 11 (9.6%) were high risk. Eighty one patients were treated with prostate brachytherapy as monotherapy, including six patients who received androgen-deprivation therapy (ADT) in combination with their brachytherapy. Twenty five patients received combination therapy, and 9 patients received trimodal therapy. Specifics of bDFS rates and PSA data are reported in the table. Of the 115 patients four had biochemical recurrence. Two patients died during the study period, both due to causes other than prostate cancer, and one patient was unwilling to obtain a PSA at the 24 month follow up time point. Conclusions: The first 115 patients who have undergone prostate brachytherapy with 131Cs at our institution have a bDFS rate of 96.4% 24 months after their procedure. With the very important caveat that only short term results are reported, 131Cs appears to be on course to achieve results comparable to those achieved with iodine 125 (125I) and palladium 103 (103Pd). [Table: see text] No significant financial relationships to disclose.
Effect of lymph node harvest for squamous cell cancer of the esophagus on survival.
Authors: Deneve Jeremiah Lee , Weber Jill M. , Hoffe Sarah E. , Sridhar Ravi , Almhanna Khaldoun , Barthel James S. , Karl Richard C. , Meredith Kenneth 
Published: February 2017

102 Background: The optimal number of lymph nodes harvested remains controversial in patients with esophageal cancer. Pathologic response to neoadjuvant therapy (NT) has demonstrated improved survival. However, little is known regarding the impact of NT or nodal harvest in patients with squamous cell carcinoma (SCC) of the esophagus. We examined the extent of LN harvest and outcome in patients who underwent esophagectomy for SCC. Methods: After IRB approval, using a comprehensive esophageal cancer database we identified patients who underwent esophagectomy between 1994-2011. Clinical and pathologic data were compared using Fisher’s exact and chi-square when appropriate while Kaplan-Meier estimates were utilized for survival analysis. Nodal strata were set at 12 (ST-1), 15 (ST-2), and 20 nodes (ST-3). Pathologic response to NT was defined as complete (pCR), partial (pPR), or non-response (pNR). Results: We identified 76 patients who underwent esophagectomy for SCC between 1994-2011. The median age was 62.5 years (40-85 months) with median follow up of 18.5 months (1-157 months). 48 (63%) were male and 28 (37%) were female. Twenty-eight patients (37%) underwent primary esophagectomy alone (PE) while 48 (63%) patients were treated with NT. Extent of lymphadenectomy had no significant impact on overall survival (OS) or disease free survival (DFS) for the entire cohort ST-1 p=0.8 and p=0.9, ST-2 p=0.5 and p=0.4, and ST-3 p=0.5 and 0.4, respectively. Among the patients who received NT, pCR was observed in 28 (58%), pPR in 14 (29)%, and pNR in 6 (13)%. When examining the degree of pathologic response to treatment, extent of LN harvest had no significant impact on OS or DFS for patients who underwent esophagectomy after NT (p=ns across all strata). Conclusions: The extent of LN harvest failed to demonstrate an overall or disease free survival benefit in patients with squamous cell carcinoma of the esophagus. Moreover, patients treated with NT also did not benefit from increased nodal resection irrespective of their pathologic response.
D-dimers as a tumor marker in GIST: Can it reduce the frequency of CT scanning in patients receiving palliative imatinib?
Authors: Seligmann Jenny F. , Hall Peter , Hamilton Patrick , Lord Simon Richard , Baxter Paul , Marples Maria , Stark Daniel P. 
Published: February 2017

119 Background: Treatment with palliative imatinib has improved outcomes in advanced GISTs, with a reported 2 year PFS of 50%. Guidelines suggest monitoring during imatinib by CT scan at 12 week intervals. There are no validated biomarkers to assist in disease evaluation. High d-dimer levels are associated with poor prognosis in several cancers and are predictive of disease progression during chemotherapy. In the diagnosis of venous thromboembolism, low D-dimer levels have a high negative predictive value (npv) for thrombosis. We investigated whether low d-dimers have a clinically useful npv for GIST progression. Methods: We retrospectively identified all patients treated with palliative Imatinib for GIST in a single tertiary referral centre using a systematic search of an electronic clinical database. Every 12 weeks during treatment patients were assessed by clinical evaluation, CT and a d-dimer measurement (HemosIL HS assay). The prognostic value of d-dimers was assessed by Cox regression. The clinical utility of d-dimers as a biomarker for radiological progression (rPD) was evaluated using radio operator curve (ROC) analysis. Results: 50 patients treated between Jan 2002 and June 2011 met criteria for inclusion. D-dimers were prognostic for progression free survival and overall survival, when analysed by level or over time (p <0.05). Over 460 clinical observations with CT and d-dimer were analysed. Scans demonstrating rPD were associated with higher d-dimer levels and a rising trend (p <0.05). D-dimer levels <1000 had a npv for rPD of 85%. An asymptomatic patient with a d-dimer level <1000 and a falling level over time was seen in 32% of observations, and had a npv for rPD of 92%. Conclusions: D-dimers may have a useful role in disease monitoring for GIST patients treated with palliative imatinib, particularly as a negative predictor of progression. This may reduce the burden of CT scanning in a useful percentage of patients but will require further validation.
Safety and feasibility of adjuvant chemotherapy with S-1 in Korean patients with curatively resected advanced gastric cancer.
Authors: Jeong Jae Ho , Ryu Min-Hee , Lee Sung Sook , Ryoo Baek-Yeol , Lee Sang Hong , Kim Kab Choong , Yook Jeong Hwan , Oh Sung Tae , Kim Byung Sik , Kang Yoon-Koo 
Published: February 2017

121 Background: Adjuvant chemotherapy with S-1 has been proven effective for patients with curatively resected advanced gastric cancer with D2 lymph node dissection in Japan. We assessed the safety and feasibility of adjuvant S-1 chemotherapy in Korean patients with stage II, III or IV(M0) gastric cancer. Methods: A total of 305 patients with stage II, III or IV(M0) gastric cancer received adjuvant S-1 chemotherapy following curative gastrectomy with D2 lymph node dissection in Asan Medical Center between October 2007 and December 2009. Adjuvant chemotherapy with S-1 was started 3-6 weeks after surgery and it was administered orally twice daily at the dose of 40 mg/m2 for 4 weeks followed by 2 weeks of rest, every 6 weeks 8 times for 1 year. We retrospectively reviewed the medical records of the patients and evaluated the safety and feasibility of adjuvant S-1 chemotherapy in Korean patients. Results: Among the 305 patients, 248 (81.3%) and 198 (64.9%) patients completed 4 and 8 cycles of adjuvant chemotherapy, respectively. The most common reasons for discontinuation of treatment were adverse event (43.9%) and recurrence (26.2%). Among the 305 patients, 75 (24.6%) patients required dose reduction because of toxicities. The most common grade 3/4 toxicities were neutropenia (12.8%), diarrhea (5.3%), abdominal pain (3.8%), and anemia (3.3%). Multivariate analysis showed that total gastrectomy (H.R. 2.50; 95% C.I. 1.32-4.72, p=0.005) and female gender (H.R. 1.95; 95% C.I. 1.03-3.66, p=0.039) were independent risk factors for grade 3/4 hematologic toxicities, and old age (>65 years) (H.R. 2.92; 95% C.I. 1.50-5.69, p=0.002) was an independent risk factor for grade 3 non-hematologic toxicities. Conclusions: Adjuvant chemotherapy with S-1 for 1 year was safe and feasible in Korean patients. Old age, female gender, and total gastrectomy were independent risk factors for severe toxicities of adjuvant S-1 chemotherapy.