bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemotherapeutic management of adrenocortical carcinoma: The M. D. Anderson Cancer Center experience
Authors: Fareau G. G. , Vassilopoulou-Sellin R. 
Published: March 2020

14592 Background: Adrenocortical carcinoma (ACC) is a rare cancer associated with a poor prognosis. We describe our experience with the effectiveness of various chemotherapies in the treatment of ACC. Methods: We performed a detailed retrospective review of every patient diagnosed with ACC at the M.D. Anderson Cancer Center between the years 1980 and 2000. We included only those patients with a histological diagnosis of ACC who had radiologically measurable disease and received chemotherapy followed by post-treatment imaging. Patients without a pathological diagnosis, serial imaging studies, or adequate follow-up were excluded from our study. In each case, we compared radiological tumor burden after a given drug or drug combination to the radiological tumor burden preceding the treatment session. Radiologist reports were used to categorize post-treatment imaging studies as showing either a decrease in tumor burden, no change in tumor burden, or an increase in tumor burden. Patients who did not have post-treatment imaging due to rapid progressive clinical deterioration were regarded as having increased tumor burden. Results: 224 patients with a diagnosis of ACC were identified in our database, of which 62 had histological confirmation and received chemotherapy with documented radiological follow-up. 38 different chemotherapeutic regimens were reviewed. Patients given single agent fluorouracil, taxol, taxotere, trimetrexate, navelbine, and patients given combination treatment with cyclophosphamide/adriamycin/cisplatin, gemcitabine/taxotere, and mitotane/cisplatin/taxol did not show any improvement. Treatment with single agent mitotane and combination VP-16/cisplatin resulted in either no change or decrease in tumor burden in over 50% of sessions. Promising trends were seen in patients treated with single agent VP-16 and carboplatinum, and with combination adriamycin/cisplatin/ifosfamide, mitotane/cisplatin, and VP-16/adriamycin/cisplatin. Conclusions: We have identified specific drugs and drug combinations of no apparent benefit in this cohort, and have also identified select agents and combinations which offer benefit. Further prospective clinical trials should focus on the use of those agents and combinations which offer benefit. No significant financial relationships to disclose.
Phase II study of intravenous vinorelbine plus hormone therapy in hormone-refractory prostate cancer
Authors: Silva E. , Silva F. 
Published: March 2020

14601 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in Phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. The purpose of this study was the investigation of the efficacy of vinorelbine and its toxicity. Methods: Patients with metastatic prostate cancer, progressive after hormonal therapy, receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day. Previous chemotherapy was allowed if stopped 6 months before. 44 received VRL according to the protocol. Inclusion criteria: hormone refractory prostate cancer patients PSA >20; performance status WHO < 2. The primary endpoint was prostate specific antigen (PSA) levels, pain, and WHO performance status. Their mean (range) age was 71 (45–80) years, their median prostate specific antigen (PSA) level was 286 (38–950) ng/ml, and the median Gleason score was 8 (7 to 9). 38 patients had had previous chemotherapy. Results: Among the 44 patients, 7 with less than 3 cycles were not evaluated. Patients received a mean (range) of 9 (3–44) cycles of therapy. 6 patients (14%) had not been dispensed prior chemotherapy and 38 (86%) had; 19 (43%) had 2 lines of chemotherapy and 19 (43%) had 1 line. The median follow-up was 13 months. There were no reported drug related Grade 3 toxicities. Only 2 patients required a blood transfusion. Tumour responses: 7 (16%); 17 (39%) PSA stable; 13 (29%) PSA progression, 7 not evaluated. Time of PSA response was 7 months; time to progression: 7 months. Conclusions: Vinorelbine (VRL) is a safe regimen in previous poly-chemotherapy treated hormone-refractory prostate cancer elderly patients and even with response and efficacy. No significant financial relationships to disclose.
Interstitial high dose rate (HDR) brachtherapy + IMRT vs. HDR monotherapy for early stage prostate cancer
Authors: Neumann T. , Mark R. , Anderson P. J. , Nair M. 
Published: March 2020

14606 Background: Transrectal Ultrasound (TRUS) guided interstitial implant for prostate cancer using High Dose Rate (HDR) + External Beam Radiation Therapy (EBRT) or IMRT has been reported with favorable results. The role of supplemental EBRT or IMRT in brachytherapy is undefined. We compare our results of HDR + IMRT vs. HDR monotherapy. Methods: Between 1997 and 2006, 276 patients with T1 and T2 localized prostate underwent TRUS interstitial implant. After discussion of treatment options, 109 patients elected HDR Implant + IMRT and 167 patients underwent HDR alone. No patient received Hormonal Blockade. Median Gleason Score was 7 (range: 4 to 10). Median PSA was 9.8 (0.60 to 39.8). In patients who received IMRT + HDR, 4500 cGy in 25 fractions was given via IMRT and 1650 cGy in 3 fractions via HDR. Our protocol for HDR alone, has called for two HDR Implants. The treatment volume received 2,250 cGy in 3 fractions prescribed to the 100% Isodose line, given over 24 hours. A 2nd implant was performed 4 weeks later, delivering a further 2,250 cGy in 3 fractions, bringing the final dose to the prostate to 4,500 cGy in 6 fractions. Results: There was no significant difference between the treatment groups with respect to T-Stage, Gleason Score, and PSA. With a median follow-up of 66 months (range: 6 months to 120 months), the overall PSA disease free survival (DFS) was 89.5% (247/276). In patients undergoing IMRT + HDR, PSA DFS was 89.0% (97/109) vs. 89.8% (150/167) for patients undergoing HDR alone (p = 0.6). The 5 year actuarial survival was 86% for the group receiving IMRT + HDR vs. 89% with HDR (log rank = 0.5). Urinary stress incontinence has occurred in 2.5% (7/276). RTOG late bladder toxicities were: 0% Grade 4, 0% Grade 3, and 3.3% (9/276) Grade 2. RTOG late rectal toxicities were: 0.4% (1/276) Grade 4, 0% Grade 3, 3.6% (10/276) Grade 2, and 4.7% (13/276) Grade 1. RTOG late rectal toxicity was higher in patients undergoing HDR + IMRT with 14.7% (16/109) of patients experiencing Grade 2 and 1 symptoms, vs. 3.0% (5/167) receiving HDR alone (p ≤ 0.01). Conclusions: We have observed no difference in PSA DFS in patients undergoing HDR vs. HDR + IMRT. Complications were similar, though RTOG Grade 1 and 2 late toxicity was higher in patients receiving HDR + IMRT. By omitting IMRT, rectal complications may be reduced. No significant financial relationships to disclose.
A phase I open-label, dose escalation study to determine the maximum tolerated dose and to evaluate the safety profile of lenalidomide with every three week docetaxel in subjects with androgen independent prostate cancer
Authors: Moss R. A. , Shelton G. , Melia J. , Mohile S. G. , Petrylak D. P. 
Published: March 2020

14618 Background: Based on the known efficacy of docetaxel (D) in Androgen Independent Prostate Cancer (AIPC), and demonstrated activity of the antiangiogenesis agent thalidomide in combination with docetaxel, a Phase I trial in patients (pts) with AIPC with evidence of progression by unidimensionally measurable disease or rising serum Prostate Specific Antigen (PSA) levels after antiandrogen withdrawal was designed. The study evaluates the combination of escalating doses of D and lenalidomide (Ln), a derivative of thalidomide with immunomodulatory and antiangiogenic properties. Pts were permitted to have no more than two prior chemotherapy regimens. Methods: Pts were given D and Ln on a q3 week dose-escalation schedule. Dose Levels of D (mg/m2): Level (L) 1 = 60 L2-L5 =75, given IVPB over 60 minutes in combination with prednisone 5mg po bid. Decadron 20 mg was given 12, 6 hrs and 15 minutes prior to D on D#1. Dose of Ln (mg/day) on D#1–14 of 21-day cycle: L 1 = 10 mg, L2= 10 mg, L3 = 15 mg, L4–20 mg L5 = 25 mg. Patient Characteristics: L1: N = 5. Median Age 66.2 yrs. Median PSA = 101.9 (range 5.9–164.0). Prior CT: none. Prior palliative RT: none. Patients with unidimensionally measurable disease: 4, all in lymph nodes. Patients with bone metastases: 5. Pre-treatment, 1 patient required narcotic analgesics. Results: Five L1 patients are evaluable for toxicity and response. Median number of cycles administered = 4 (range 2–5). Toxicity: There have been no Grade (G) 3 or 4 toxicities. Anti-tumor activity: Two pts (40%) have had a greater than 50% decline in serum PSA on 2 consecutive measurements at least 2 weeks apart. Of 4 pts with unidimensionally measurable disease, all have stable disease by RECIST criteria. Conclusions: At L1, D + Ln has been well tolerated in AIPC. Further dose escalation to L2 and above is planned. [Table: see text]
Prognostic factors for the recurrence of renal cell carcinoma after radical nephrectomy
Authors: Ohlmann C. H. , Schneider T. , Wille S. , Engelmann U. , Heidenreich A. 
Published: March 2020

14629 Background: Recurrence of renal cell carcinoma depends mainly on tumor stage at the time of radical nephrectomy and increases with increasing T-stage. Up to 30% of patients with T1–2 tumors will experience local or distant recurrence. Recommendations for the follow-up include chest x-ray every 6 months for stages T1–4 and abdominal CT-scan for pT3–4 for the first 3 years. The aim of our study was to identify prognostic factors predicting recurrence of RCC in order to individualize follow up strategies. Methods: We retrospectively analyzed the charts of 177 patients with RCC who underwent radical nephrectomy. In 163/177 (92%) of the patients the histology revealed renal cell carcinoma. The median-follow up was 4.5 (1–6) years. The prognostic significance of histology, gender, age, c-reactive protein, hemoglobin, hematuria, gross hematuria, weight loss, flank pain and metastases at the time of surgery for risk of recurrence was calculated by uni- and multivariate analysis. Cancer specific survival (CSS) was analyzed by the Kaplan-Meir method. Results: Logistic regression analysis identified presence of metastases at time of surgery (p ≤ 0.0005), hematuria (p ≤ 0.0005) and flank pain (p = 0.011) as independent prognostic factors for the recurrence of RCC. The risk of recurrent disease is 33.5% with one, 70 to 83% with two and 95.6% with the presence of all 3 markers. 3-year CSS is 69% vs. 82% in symptomatic vs. asymptomatic patients (p = 0.1352), 45% vs. 90% in M1/N1 vs. M0/N0 (p = 0.0001) and 78% vs. 88% in pT3b vs. <pT3b (p = 0.0102). Conclusions: In our study we were able to identify prognostic factors for the recurrence of renal cell carcinoma. Based on this model the follow-up of patients can be individualized according to the risk for recurrence after radical nephrectomy. No significant financial relationships to disclose.
Cost-effectiveness of zoledronic acid vs. pamidronate in the management of hormone refractory prostate cancer (HRPC) patients with bone metastases
Authors: Botteman M. , Barghout V. , El Ouagari K. 
Published: March 2020

14660 Background: Canadian guidelines recommend zoledronic acid (ZA) (4 mg every 3 weeks) in patients with hormone HRPC and asymptomatic or minimally symptomatic bone metastases to reduce skeletal-related events (SRE). However, IV pamidronate (90 mg every 3 weeks) (PA) is also routinely used in this setting in spite of no significant improvement in occurrence of SRE or pain compared to NT. Objectives: To assess the cost effectiveness of ZA, PA, or no bisphosphonate therapy (NT) in the management of prostate cancer patients with bone metastases in Canada. Methods: A literature-based decision analytic model was developed to estimate the incremental cost and quality-adjusted life years (QALY) associated with the 3 treatment options. The model included assumptions about SREs, mortality, drug and administration costs, cost of SREs, reduced quality of life due to SRE and bone pain, and therapy duration. Sensitivity analyses considered several scenarios in which various assumptions were used regarding treatment efficacy and QALY gains due to pain relief and SRE prevention. All costs were expressed in Canadian dollars (2004). Results: The cumulative number of SREs over a patient’s remaining lifetime (1.9 years) was estimated at 2.69 for PA and NT patients and 1.76 for ZA. Total discounted costs were $11,918 for NT, $17,593 for PA, and $19,312 for ZA. Compared with patients receiving NT or PA, quality-adjusted survival increased by 0.094 (range depending on scenario considered: 0.072 to 0.106) QALY per patient for those on ZA compared to PA or NT. Compared to NT, ZA resulted in a cost per QALY gained of $78,366 (range: $50,717 to $101,831). Compared to PA, ZA resulted in a cost per QALY gained of $18,343 (range: $2917 to $23,835) per QALY gained. PA was more expensive than NT but did not improve patient-related outcomes. Conclusions: For HRPC patients with bone metastasis, zoledronic acid appears to be the only clinically valuable and economically acceptable option in Canada with a cost effectiveness likely better than previously reported. No significant financial relationships to disclose.
Neoadjuvant chemotherapy in advanced epithelial ovarian oancer (EOC): A phase III randomized study
Authors: Kumar L. , Hariprasad R. , Kumar S. , Bhatla N. , Shukla N. , Thulkar S. , Singh R. 
Published: March 2020

15000 Background: We compared upfront surgery to upfront chemotherapy in patients with advanced EOC (stage IIIC and IV (pleural effusion only). Factors- optimum debulking (residual disease ≤1cm) rate, surgical morbidity, chemotherapy toxicity, survival and quality of life (QOL) were analyzed. Methods: Between Oct.2001 and Oct. 2005, 90 newly diagnosed patients with advanced EOC have been randomized to upfront surgery followed by six cycles of paclitaxel + carboplatin (TC) (Arm A) or upfront chemotherapy - 3 cycles (TC) followed by surgery then 3 more cycles of TC. Eligibility criteria included- age 18 to 65 years, biopsy or cytological proven diagnosis of EOC and adequate hematological, renal, liver and cardiac functions. Upper and lower GI endoscopy and serum CEA was done in all patients to rule out GIT primary. QOL was assessed using FACT-O questionnaire at baseline, postop, post 3 cycles and post 6 cycles chemotherapy. Results: 78 of 90 patients have completed the treatment. Among 74 evaluable patients, optimal debulking rate was higher in the neoadjuvant chemotherapy arm (83% vs 13%, p < .001). Blood loss during surgery (340 ml vs.485 ml, p < . 008), mean operating time (69 minutes vs. 77 minutes, p = 0.22), post op infection rate (3% vs 17.5%, p < .07), & hospital stay (9 days vs. 12.4 days, P = 0.04) were lower in the chemotherapy arm. Operative mortality was higher in upfront surgery arm (7.7% vs 3.3%, p = .38). QOL score was higher post 3 cycles and post 6 cycles in the upfront chemotherapy arm (p < . 0001). Grade III-IV GI toxicity (4.5% vs 3.8%) and myelo-suppression (7% vs 9%) was similar in two arms. At a median follow up of 33 months, Overall (41 vs 42 months) & progression-free survival (35.3 vs 29 months,p = ns) are not significantly different in upfront chemotherapy vs upfront surgery arms, respectively. Conclusions: Upfront chemotherapy in advanced EOC results in significantly higher optimum debulking rate with reduced surgical morbidity and mortality, Quality of life score was also higher. Present study favors role of “upfront chemotherapy” in patients likely to have residual disease >1cm and higher morbidity with upfront surgery. No significant financial relationships to disclose.
The therapeutic benefit of extensive lymphadenectomy in advanced stage ovarian cancer
Authors: Berek J. S. , Karnik Lee N. , Cheung M. K. , Osann K. , Husain A. , Teng N. N. , Kapp D. S. , Chan J. K. 
Published: March 2020

15010 Background: To determine if extent of lymphadenectomy affects the disease-specific survival of women with advanced-stage ovarian cancer. Methods: Demographic and clinico-pathologic information were obtained from the Surveillance, Epidemiology and End Results Program from 1988–2001 and analyzed using Kaplan-Meier methods and Cox proportional hazards regression. Results: Of the 15,320 women with stage IIIB-IV disease, 763 (5.0%) had stage IIIB, 5,266 (34.4%) stage IIIC, and 9,291 (60.7%) had stage IV disease. The median age was 66 (range: 1–101). 13,251 (86.5%) were White, 1,049 (6.9%) Black, 716 (4.7%) Asian, and 304 (1.9%) were Other. Of the patients who underwent a lymphadenectomy, the median number of nodes resected was 6 (range: 1–90). We divided our study group 3 groups based on the extent of lymphadenectomy (0, <10, 10–20, and >20). In the overall study group, the extent of lymphadenectomy improved the survival from 21.1%, 40.5%, 45.1% to 46.0%, respectively (p < 0.001). Patients with stage IIIB, IIIC, and IV disease had an improvement in survival associated with lymphadenectomy (see table ). In patients with non-clear cell epithelial carcinoma, the extent of lymphadenectomy was associated with improved survivals 20.9%, 39.8%, 45.4%, and 45.9%, respectively (p < 0.0001). Moreover, those with clear cell cancers (p = 0.0001), germ cell (p = 0.001) and sarcomas of the ovary (p = 0.02) also had a survival benefit; however no benefit was demonstrated in sex cord stromal tumors (p = 0.99). In multivariate analysis, a more extensive lymphadenectomy remained significant as an independent prognostic factor for improved survival after adjusting for all other independent prognostic factors including age, year of diagnosis, surgery, histology, stage, and grade. Conclusions: Our findings suggest that the extent of lymphadenectomy improves the disease-specific survival of women with stage IIIB-IV ovarian cancer. This benefit was demonstrated in epithelial, germ cell, and sarcomas of the ovary. [Table: see text] No significant financial relationships to disclose.
Significance of necrosis in grading of anaplastic oligodendroglial tumors: A clinicopathological and genetic study of 916 high-grade gliomas
Authors: Miller C. R. , Dunham C. P. , Scheithauer B. W. , Perry A. 
Published: March 2020

1502 Background: High-grade gliomas (HGG, WHO grades III-IV) are morphologically and genetically diverse, with survivals ranging from months to decades. Although WHO 2000 grading criteria are well established for pure astrocytomas [anaplastic astrocytoma (AA) and glioblastoma (GBM)], those for oligodendroglial neoplasms [anaplastic oligoastrocytoma (AOA) and oligodendroglioma (AO)] remain subjective, there being a debate regarding the existence of a grade IV variant based on the finding of necrosis, particularly with pseudopalisading (PPN). Methods: Overall survival of 916 adult (>20 yr) patients diagnosed between 1990 and 2005 with supratentorial HGG (77 AA, 481 GBM, 183 AOA, 175 AO) was analyzed by uni- (log-rank) and multivariate (Cox proportional hazards) models for significance of the following factors: microvascular proliferation, necrosis, patient age, surgery (stereotactic vs. open), location, primary vs. secondary tumor, year of diagnosis, and chromosome 1p and 19q losses by fluorescence in situ hybridization. Results: Necrosis was a statistically significant predictor of poor survival on multivariate analyses in AOA (P=0.035), but not in AO (log-rank P=0.048, Cox P=0.9), while PPN showed a trend towards significance on multivariate analysis only in AOA (P=0.096). Other independent predictors on multivariate analysis included age, grade, surgery type, and year of diagnosis for AA/GBM and age, primary tumor, and 1p/19q codeletion for both AOA and AO (P<0.05). Median survival for AOA patients whose tumors featured necrosis (20.7 mo) was significantly worse than their counterparts lacking necrosis (>104 mo); survival of the latter was more similar to that of AO (83.5 mo), whereas in the former it was better than GBM (10.5 mo) (log-rank P<0.0001). Conclusions: Stratification of oligoastrocytomas, but not of pure oligodendrogliomas, into grades III (AOA) and IV (GBM with oligodendroglial features) on the basis of necrosis is prognostically justified and is more accurate than the current approach of using a single anaplastic grade. These data provide impetus for the modification of present WHO criteria. No significant financial relationships to disclose.
Concurrent chemoradiation (CCR) for locally advanced or relapsed vulvar carcinoma (VC) treatment: An alternative to pelvic exenteration (PE)
Authors: Porcela H. , Gianni S. , Alvarez A. M. , De Dios D. , Mickiewicz E. , Roth B. , Cinat G. , Menendez P. , Bonomi M. 
Published: March 2020

15021 Background: PE is the standard treatment for locally advanced or relapsed VC that involves the anus or rectovaginal wall, with high morbidity and the consequent loss of Qol. Objective: Locoregional response, toxicity, disease free survival (DFS) and survival (SV) achieved with concurrent chemoradiation in locally advanced or relapsed VC was prospectively evaluated. Methods: From 7/93 to 05/05, 32 pts which would have required some kind of PE were treated with mitomycin C (10 mg./m2 d1) + 5-Fluoruracil (800 mg/m2 d 1–4) IV continuous infusion, plus concurrent external radiotherapy (50 Gy) to the vulva, pelvis and groin. An additional boost (15–20 Gy) was added when a less than complete clinical response (CR) was achieved. Multiple biopsies of the tumor bed were performed to confirm complete pathologic responses (CPR). Results: 30 pts (94%) completed treatment as planned. Overall, locoregional response was obtained in 25/30 (83.3%) pts: 20 (66.6%) CR, 5 (16.6%) partial response (PR). 3 (10%) pts had stable disease and 2 (6.6%) progresive disease. 14/30 (46.6%) had CPR. Radical vulvectomy or radical local excision was performed in 7 pts for residual disease after CCR (4/6 with CR and microscopic residual disease and 3/5 with PR), 2 pts with PR were lost after having completed CCR and 2 pts with CR and microscopic residual disease refused further treatment. None of the responding patients required PE. Treatment was well tolerated with mild to moderate toxicity, attributed to radiotherapy. No treatment deaths were recorded. 28 pts with a median follow-up of 25.5 months (range 6–126) showed a 5-year cumulative DFS (34%) and SV (49%). Conclusion: CCR is a safe therapeutic option with results comparable to those obtained with PE, with significant improvement of Qol. CCR has become the standard treatment for locally advanced or relapsed VC at our center. No significant financial relationships to disclose.