bluuebunny/crossref_metadata_2025_split huggingface dataset:
Routine interval computed tomography in detecting new soft tissue disease in patients with androgen-independent prostate cancer (AIPC) and only bone metastasis
Authors: Wu S. , Jones E. , Gulley J. , Arlen P. , Chen C. , Figg W. , Dahut W. 
Published: March 2020

4621 Background: Bone is the most common metastatic site in AIPC and the only site of metastasis for many patients. However, some pts with only bone metastasis will eventually develop soft tissue disease. Thus many clinical trials include CT monitoring to exclude new soft tissue disease as the only manifestation of disease progression. The true incidence of the asymptomatic development of soft tissue metastases without PSA or bone scan progression is unknown. Here we have identified pts with bone metastasis only at the time of protocol enrollment. We analyzed their disease progression pattern to determine the utility of routine interval CT scans. Methods: We reviewed 100 pts with metastatic AIPC from three phase II clinical trials (docetaxel/thalidomide, docetaxel/vaccine, and ketoconazole/alendronate) between 1995 and 2004. Pts were assessed every 4 weeks with PSA measurement. CT and bone scans were performed 2 months after start of the trial and then at least every 3 months. Median follow-up time was 8 months (1–44 months). The pts with bone metastasis only were examined for the occurrence of soft tissue diseases by subsequent CT scans in association with bone scan and PSA. Results: Of 100 pts with metastatic AIPC, 33% had soft tissue disease alone or soft tissue and bone disease. 67% had no soft tissue involvement identified by CT but had bone metastasis revealed by bone scan. Of the pts with only bone metastasis, 3% (2 pts) developed new soft tissue disease. One pt developed new right illiac fossa lymphadenopathy after 8 months, and another a peri-rectal mass after 12 months. The one with new lymphadenopathy also had multiple new bone lesions identified by bone scan and PSA progression. The one with a peri-rectal mass had PSA progression and a palpable abnormality. Conclusions: The incidence of asymptomatic new soft tissue disease as the only manifestation of disease progression appears to be quite low in pts with only bone metastasis. Scheduled interval examination with CT to exclude new soft tissue disease does not appear to be warranted. CT scans should probably only be done at the time of disease progression shown by bone scan/PSA or when there are clinical signs or symptoms of new soft tissue disease. No significant financial relationships to disclose.
Delaying metastatic disease progression in locally advanced disease − Results from the Early Prostate Cancer program at a median follow-up of 7.4 years
Authors: Wirth M. P. , See W. A. , McLeod D. G. , Iversen P. , Morris T. , Armstrong J. 
Published: March 2020

4629 Background: Progression of prostate cancer to bone metastases impacts seriously on patients (pts)’ quality of life and increases treatment costs. The 3rd analysis of the Early Prostate Cancer (EPC) program revealed that bicalutamide (CASODEX) 150 mg plus standard care (radiotherapy [RT], radical prostatectomy [RP] or watchful waiting [WW]) significantly improved progression-free survival (PFS) vs standard care alone in locally advanced disease. Adjuvant bicalutamide 150 mg also improved overall survival for RT pts with locally advanced disease. Here, we report an exploratory analysis of the effect of bicalutamide on delaying bone metastases in pts with locally advanced disease in the EPC program. Methods: The EPC program comprises 3 trials in which pts (n = 8113) were randomized to standard care plus bicalutamide 150 mg or placebo. This exploratory analysis included only pts with locally advanced disease (T3–4, any N; or any T, N+; bicalutamide n = 1367, placebo n = 1315). Distant metastases were assessed by bone scan. Metastatic PFS was defined as time from randomization to either first bone scan-confirmed progression or death in the absence of bone-scan data. A Cox proportional hazards regression model was used for the WW and adjuvant subgroups; each was analyzed separately with covariates for trial, treatment, prior therapy, baseline prostate-specific antigen level, and tumor grade. Results: At 7.4 years’ median follow-up, bicalutamide significantly improved metastatic PFS vs placebo (hazard ratio [HR] 0.64, p < 0.001 for WW; HR 0.77, p = 0.005 for RT/RP; table). The most common adverse events were gynecomastia and breast pain. Conclusion: Addition of bicalutamide 150 mg to standard care significantly reduced the risk of distant metastases in locally advanced prostate cancer, irrespective of standard care. Both the efficacy and tolerability of treatment must be considered, and therefore, bicalutamide is an option for men with locally advanced prostate cancer. [Table: see text] [Table: see text]
Phase II study of neoadjuvant docetaxel and androgen suppression (AS) plus radiation therapy (RT) for high-risk localized prostate cancer (HRLCaP)
Authors: McKenzie M. R. , Chi K. N. , Neville A. , Ellard S. , Baerg B. , Ruether D. , Winquist E. , Segal R. , Lukka H. 
Published: March 2020

4631 Background: Docetaxel increases survival in hormone-refractory prostate cancer and is active in hormone-sensitive disease. In HRLCaP, improvement upon AS plus RT is required, as many patients eventually develop metastases. This trial’s objective was to assess the tolerability of neoadjuvant docetaxel plus AS and RT in men with HRLCaP. Methods: Fifty-four men with newly diagnosed previously untreated HRLCaP were accrued to a Phase II single-arm, 2-stage, open-label study involving 7 Canadian centres. All were to receive 3 years of AS (LHRH-agonist + antiandrogen for 4 weeks). Chemotherapy started week 5. Twenty-four men received docetaxel 35 mg m2 iv weekly × 6 q8 weeks for 2 cycles, RT starting week 25. After protocol revision, 30 men received docetaxel 75 mg m2 iv q3 weekly for 4 cycles, RT starting week 21. The primary endpoint was unacceptable toxicity (UT), defined as ≥Grade 3 non-hematologic toxicity (except nausea/vomiting, tearing, short-term fatigue, and easily-controlled diarrhea), grade 4 thrombocytopenia, grade 4 neutropenia lasting >7 days, febrile neutropenia, or toxicity-related RT change (delay>2 weeks, >25% dose reduction). Results: Median age was 68 (49–79) years. Median iPSA was 19.15 (2.8–138) μg/L. Gleason Score and T-stage were ≥8 and ≥T3a in 70.4% and 42.6%, respectively. All patients have completed RT. Adverse events were as expected for docetaxel. UT occurred in 8 patients (14.8%), including 5 with qweekly docetaxel (Grade 3 acute RT-related genitourinary toxicity - 3, Grade 3 docetaxel hypersensitivity - 1, Grade 3 fatigue >2 weeks - 1) and 3 with q3 weekly docetaxel (Grade 3 acute RT-related genitourinary toxicity - 1, febrile neutropenia - 1, Grade 4 neutropenia >7 days - 1). The following table summarizes PSA response to neoadjuvant treatment. Conclusions: Neoadjuvant AS and docetaxel plus RT in men with HRLCaP appeared well tolerated. Patients will be followed for other outcomes. This approach will be tested in a phase 3 trial. [Table: see text] No significant financial relationships to disclose.
Response to low-dose ketoconazole and subsequent dose escalation to high-dose ketoconazole in patients with androgen-independent prostate cancer
Authors: Nakabayashi M. , Xie W. , Regan M. M. , Jackman D. M. , Kantoff P. W. , Oh W. K. 
Published: March 2020

4646 Background: High dose ketoconazole (HDK) in combination with steroids has been recognized as an effective secondary hormonal therapy in androgen independent prostate cancer (AIPC). However, HDK causes more severe adverse events than low dose ketoconazole (LDK). Relatively little is known about the efficacy of LDK in AIPC. We evaluated the efficacy of LDK and of subsequent dose escalation from LDK to HDK as secondary hormonal therapy in patients with AIPC. Methods: We retrospectively identified patients with AIPC in a single institution treated with LDK (200 mg PO TID) as secondary hormonal therapy with or without concomitant steroids. Additionally, patients were identified who received dose escalation to HDK (400 mg PO TID) after experiencing a rising prostate-specific antigen (PSA). Results: 138 patients were eligible for the study. Median age was 64 years (range: 41–84); median PSA at initiation of ketoconazole was 37.4 ng/ml (range: 0.8–2279). Patients received LDK as either second (25.4%), third (50.0%) or fourth (21.7%) line hormonal therapy. Thirty-nine of 138 patients (28.3%, 95% CI 20.9%–36.6%) treated with LDK treatment experienced PSA declines ≥50%. Median duration of LDK was 6.4 months in responders and 2.9 months in non-responders. Dose escalation to HDK subsequently was performed in 55 (40%) patients, seven of whom (12.7%) demonstrated a subsequent PSA decline ≥50% (5 LDK responders and 2 LDK non-responders, respectively). Overall time to progression with LDK with or without dose escalation was 3.5 months (range 0.1+–61 months). The most common reversible adverse effect on LDK was grade 1 or 2 fatigue (12.3%). 41.8% of dose escalation group experienced either aggravation or development of toxicities. The most common toxicities on HDK were nausea (16.4%) and fatigue (14.5%). Conclusions: LDK is associated with a PSA response rate comparable to HDK as secondary hormonal therapy in patients with AIPC, and appears to be less toxic. Few patients responded to the dose escalation from LDK to HDK but durable additional responses occurred in some. No significant financial relationships to disclose.
Survival (S) of ovarian cancer (OC) patients (pts) treated on SWOG9701/GOG178: 12 versus (v) 3 cycles (C) of monthly single-agent paclitaxel (PAC) following attainment of a clinically-defined complete response (CR) to platinum (PLAT)/PAC
Authors: Markman M. , Liu P. , Wilczynski S. , Monk B. , Copeland L. , Alberts D. 
Published: March 2020

5005 Background: This phase 3 trial was closed by the SWOG Data Safety and Monitoring Committee (DSMC) when a prospectively-defined interim analysis revealed a highly statistically significant difference in progression-free S (PFS) (28 v 21 months [M]; p = 0.0023; hazard ratio [HR] 2.31) (JCO 2003; 21:2460). At study closure, there were insufficient deaths to describe the impact of 12-C of PAC on overall S (OS). Methods: Eligibility included OC or primary peritoneal cancer, attainment of a CR to PLAT/PAC, and ≤ grade 1 neuropathy. Pts entered into the trial (n = 296) received either 12-C or 3-C of PAC (175 mg/m2 q-28 days), and were then observed until progression. Results: Of the 146 pts on the 3-C arm, 9 (6%) actually received prolonged PAC (> 3-C) following closure of the study by the DSMC. Median (12-C v 3-C; intention-to-treat analysis): updated PFS (all pts) 22 v 14 M, p = 0.01; OS (all pts) 53 v 46 M, p = 0.27. Exploratory analysis (Cox models adjusting for stratification factors): 12-C v 3-C HR 0.59 (p = 0.03) if baseline CA-125 ≤ 10 (n = 175), and 1.25 (p = 0.34) for baseline CA-125 >10 (n = 121). The treatment v baseline CA-125 interaction was statistically significant (Cox model p = 0.03). Conclusion: OS was not significantly different between 12-C v. 3-C of PAC, either because (a) treatment at relapse equalized OS; (b) the sample size was insufficient to reveal a difference; (c) the crossover of pts from 3-C to longer treatment masked a potential difference; or (d) treatment was possibly prematurely discontinued at 12-C in pts who had not progressed (suggested by a previously reported exploratory analysis -JCO 2003; 21:2460). Of interest, an exploratory analysis strongly suggested an improvement in S for pts receiving 12-C of PAC if the baseline CA-125 level was ≤10, those individuals likely to have the smallest volume of clinically-undetectable residual OC when single-agent “maintenance” PAC was initiated. No significant financial relationships to disclose.
Laparoscopic extraperitoneal para-aortic lymphadenectomy in patients with locally advanced cervical cancer: Histopathologic findings and correlation with PET-CT imaging studies
Authors: Coleman R. L. , Ramirez P. T. , Slomovitz B. M. , Levenback C. 
Published: March 2020

5014 Objective: To evaluate the safety and feasibility of laparoscopic extraperitoneal para-aortic lymphadenectomy and to correlate histopathologic findings and preoperative PET-CT imaging in patients with locally advanced cervical cancer. Methods: We performed a prospective study of patients with locally advanced cervical cancer. Patients enrolled underwent laparoscopic extraperitoneal para-aortic lymphadenectomy prior to chemoradiation at our tertiary cancer center from April 2004 to June 2005. All patients had a preoperative CT scan and PET-CT scan. Results: 12 patients were enrolled. One patient did not undergo surgery. No patient had evidence of metastatic disease to the para-aortic area by preoperative CT scan. The median age was 48 years (range, 35–67). 10 patients were diagnosed with squamous cell carcinoma, one patient with adenocarcinoma, and one patient with transitional cell carcinoma. The stage distribution was: IB2 (3), IIA (1), IIB (4), IIIA (1), IIIB (3). The median BMI was 26 (range, 18.6–29.7). Two (18%) of 11 patients had a positive preoperative PET-CT imaging study for disease in the para-aortic lymph nodes. The median time of surgery was 162 minutes (range, 52–247). The median blood loss was 25 mL (range, 10–100). There were no intraoperative complications. No patient required intraoperative blood transfusions. The median length of postoperative stay was 1 day (range, 1–2). There were two patients who developed postoperative lymphocysts requiring drainage. The median number of lymph nodes removed was 11 (range, 4–17). A total of 2 (18%) of 11 patients had evidence of histologically confirmed lymph node metastases. Of these, only one patient had evidence of disease by PET-CT scan. Only one of the two patients with a positive PET-CT scan for disease in the para-aortic nodes, actually had disease confirmed histopathologically. The sensitivity and specificity of PET-CT scan is 50% and 89%, respectively. Conclusions: Laparoscopic extraperitoneal para-aortic lymphadenectomy is safe, feasible and appears to increase the precision of identifying occult metastasis. Further patient accrual will be needed to evaluate the ultimate utility of PET-CT imaging in this setting. No significant financial relationships to disclose.
Long-term impact of chemotherapy on early stage ovarian cancer patients
Authors: Matulonis U. A. , Kornblith A. , Lee H. , Bryan J. , Gibson C. , Wells C. , Lee J. , Sullivan L. , Penson R. T. 
Published: March 2020

5024 Background: Quality of life (QOL) assessments in early stage (stage I and II) ovarian cancer survivors (CS) are limited and have to date not focused on CS who have received adjuvant platinum- and taxane-based chemotherapy (CT). Methods: 55 early stage ovarian patients (pts) were identified from patient logs from the Dana-Farber Cancer Institute and Massachusetts General Hospital. 54 pts. received CT. QOL and long-term medical sequelae were measured in pts who were > 3 years from diagnosis and had no evidence of recurrent cancer. Pts were interviewed by phone, and the following surveys were administered: EORTC QLQ-C30 (EORTC) and QLQ-OV28 (OV-28), MHI-17, CALGB sexual functioning, GOG Neuropathy, FACT Fatigue, Beck’s Hopelessness, Fear of Recurrence (FOR), Dyadic Adjustment Scale (DAS), PCL-C post-traumatic stress disorder (PTSD), Unmet Needs, FACT-Spirituality (FACT-Sp), complementary therapy use, and MOS Social Support (MOS). Results: 55 pts were interviewed (mean age 58 yrs, range 34 to 77 yrs). Mean time between diagnosis and interview was 5.6 yrs. CS reported significantly higher MHI-17 scores than the population norm, and higher MHI-17 scores were associated with better overall QOL (EORTC, r = 0.57, p < 0.0001), increased social support (MOS, r = 0.54, p < 0.0001), and better marital relationships (DAS, r = 0.42, p < 0.001). Sexual problems (1.57 out of 6) and unmet needs (1.5 out of 14) were minimal. FOR was correlated with lowered overall QOL (EORTC, r = −0.63, p < 0.0001), increased abdominal symptoms (OV-28 abdominal scale, r = 0.48, p < 0.0002), increased hopelessness (Beck’s, r = 0.46, p < 0.0005), and increased spirituality (FACT-Sp, r = −0.57, p < 0.0001). CS were using 5.4 complementary therapies for QOL purposes and 5.8 for cancer treatment. Minimal negative socioeconomic impact was observed in CS (0.16 out of 4). However, 12.5% of pts had scores indicative of a diagnosis of PTSD. Conclusions: Long-term QOL follow-up of early stage ovarian cancer survivors demonstrated minimal long-term symptoms, excellent mental health, minimal unmet needs, and minimal socioeconomic impact. No significant financial relationships to disclose.
Phase II study of DMXAA combined with carboplatin and paclitaxel in recurrent ovarian cancer
Authors: Gabra H. 
Published: March 2020

5032 Background: DMXAA (AS1404) is a small-molecule vascular disrupting agent, which in animal models shows additive or supra-additive effects with cytotoxics, including taxanes and platinum agents. This phase II study evaluated DMXAA in combination with carboplatin and paclitaxel in recurrent platinum-sensitive ovarian cancer patients with a progression-free interval of more than 6 months after response to platinum-based chemotherapy. Methods: Patients had first diagnosed disease FIGO stage Ic-IV, with presence of recurrent disease confirmed by imaging. Patients were randomised 1:1 to receive up to 6 cycles of carboplatin (AUC 6 mg/ml × min) and paclitaxel (175 mg/m2) with or without DMXAA (1200 mg/m2). Safety assessments included EKG, adverse events, laboratory screens and ophthalmic exam. Efficacy endpoints are objective response rates, time to progression, duration of response and stable disease, and median and 1-year survival. Results: 55 patients have been enrolled to date from a planned total of ∼70. Initial safety findings in the two arms are comparable. Preliminary investigator-assessed RECIST response data show the following unconfirmed outcomes: of 17 patients in the DMXAA arm, there are 10 with partial responses (PRs), 7 with stable disease (SD) and 0 with progressive disease (PD); of 14 patients in the control arm, there are 8 PRs, 6 SDs and 0 PDs. Conclusions: Initial safety findings suggest that addition of DMXAA to standard doses of carboplatin and paclitaxel did not add significantly to toxicity. Efficacy assessments are ongoing to determine the value of the triple combination in recurrent ovarian cancer. No significant financial relationships to disclose.
Overexpression of the osteopontin correlates with the aggressiveness of endometrial cancer
Authors: Cho C. , Kwon S. , Ramachandran S. , Kwon S. , Kwon K. , Cha S. , Do Y. 
Published: March 2020

5038 Background: To test the hypothesis that expression of osteopontin (OPN), an integrin-binding glycoprotein, can independently predict the potential aggressiveness of endometrial cancer. We studied OPN expression in endometrial cell carcinomas and correlated OPN expression levels with clinicopathologic tumor features. Methods: The status of OPN expression in benign and malignant endometrial cancer cell lines and tissues was analyzed by Western blot and immunohistochemistry. Nonparametric Spearman’s correlation coefficient method was used to assess the statistical significance of the correlation between clinicopathologic characteristics of tumor and OPN expression. Results: An increased expression of OPN was observed in the endometrial cancer compared to normal endometrial tissue samples. When the level of OPN in normal tissue was set at 1, its level in benign endometrial hyperplasia was slightly increased at 1.2, whereas the OPN level in the highly malignant endometrial carcinoma tissue was greatly increased by nearly 3- 5 folds. Amongst the 70 cases examined immunocytochemically, of the 23 grade 1 endometrial carcinomas, 6 were unstained and 12 stained weakly positive (+). For the 20 grade 3 or serous type endometrial carcinomas analyzed, 8 (40%) stained strongly positive (+++), 8 (40%) stained moderately positive (++) and 1 stained weakly positive (+). These results showed that the level of OPN expressed between grade 1 and grde 3 or more was significantly different (Spearman’s correlation coefficient method, p = 0.001). Kaplan-Meier survival analysis showed that the increased level of OPN expression was significantly associated with reduced survival time of the patients. Conclusions: The results suggest that the increased OPN level may be involved in the malignant transformation of endometrial adenocarcinoma cells and OPN expression level is an important determinant for patient survival. No significant financial relationships to disclose.
Exemestane in advanced and recurrent endometrial carcinoma. A phase II study
Authors: Nordstrom B. , Salmi T. , Mirza M. , Abeler V. , Kristensen G. 
Published: March 2020

5042 Background: Most entrometrial adenocarcinomas of the endometrioid type express estrogen receptors and are potentially hormone sensitive. The aim of this phase II study was to evaluate the responsiveness of these tumors to treatment with Exemestane, an aromatase inhibitor. Methods: So far, 31 patients have been recruited to this ongoing study. Patients had to have a measurable tumor. Evaluation of response by CT was performed every 3 months. Evaluation of estrogen receptors (ER) was performed by immunohistochemistry and was positive in 17 patients, negative in 5 and not performed in 6 of the 28 patients evaluable for response. Treatment was given with Exemestane 25 mg orally daily. Results: Radiotherapy had been given as part of the initial therapy to 16 patients. Before inclusion into the study, 22 patients had received chemotherapy and 7 of these had also received hormonal treatment with gestagens for relapse. Response to Exemestane treatment was evaluable in 28 patients. In 17 patients with ER positive tumors, 1 showed a complete response, 1 partial response and 6 have had stable disease for 3+ months (3 patients), 6+ months (2) and 9+ months (1). The treatment was well tolerated with no major toxicity. Updated response rates will be presented. Conclusions: Treatment with Exemestane orally showed effect in patients with ER positive tumors in this heavily pre-treated group of patients with endometrioid adenocarcinoma of the endometrium. No significant financial relationships to disclose.