bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concurrent chemoradiotherapy with cetuximab plus twice-weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal squamous cell carcinoma.
Authors: Lin C. , Hsu C. , Cheng J. C. , Yen C. , Shiah H. , Lee J. , Wang H. , Yeh K. , Cheng A. , Lee Y. 
Published: February 2017

79 Background: We investigated the efficacy and safety of adding cetuximab into twice-weekly paclitaxel/cisplatin-based concurrent chemoradiotherapy (CCRT), followed by surgery, for patients with locally advanced esophageal squamous cell carcinoma (ESCC). Methods: Patients with operable ESCC (T3N0-1M0 or T1-3N1M0 or M1a) were treated with paclitaxel (35 mg/m2 1 h on days 1 and 4/week), cisplatin (15 mg/m2 1 h on days 2 and 5/week), cetuximab (400 mg/m2 2 h on day -5, then 250 mg/m2 2 h on day 3/week) and radiotherapy (2 Gy on days 1-5/week). When the accumulated radiation dose reached 40 Gy, the feasibility of esophagectomy was evaluated for all patients. In patients for whom esophagectomy was not feasible, CCRT was continued to a radiation dose of 60-66 Gy. Results: Sixty-two patients with ESCC were enrolled, and the majority had T3N1M0 or M1a tumors by endoscopic ultrasonographic staging (94%). All patients received CCRT to 40 Gy. Forty-three patients underwent surgery, and 17 patients continued definitive CCRT to 60-66 Gy. Of the scheduled doses of paclitaxel, cisplatin, and cetuximab, 80%, 79%, and 99% were given, respectively. The intent-to-treat pathological complete response rate was 24% (15/62) (95% confidence interval: 13-35%). At the median follow-up of 13.3 months, the one-year progression-free and overall survivals were 76% and 63%, respectively. The most common grade 3/4 toxic effects were leukopenia (51%), neutropenia (15%), esophagitis (19%), and infection (12%). Grade 1, 2, and 3 skin rash occurred in 59%, 36%, and 2% of patients, respectively. Grade 1, 2, 3, and 4 hypomagnesemia occurred in 14%, 5%, 0%, and 5% of patients, respectively. Conclusions: Adding cetuximab to twice-weekly paclitaxel/cisplatin-based CCRT prior to esophagectomy is an active and tolerable treatment for locally advanced ESCC. No significant financial relationships to disclose.
Phase II study of everolimus in patients with advanced gastric cancer refractory to chemotherapy including fluoropyrimidine and platinum.
Authors: Yoon D. , Ryu M. , Park Y. , Lee H. , Lee C. , Lee J. , Ryoo B. , Chang H. , Kim T. , Kang Y. 
Published: February 2017

93 Background: To evaluate feasibility with activity and toxicities of everolimus, a novel inhibitor of mammalian target of rapamycin (mTOR), in patients with advanced gastric cancer (AGC) who failed chemotherapy including both fluoropyrimidine and platinum (FP). Methods: Fifty-four patients were enrolled between Jul 2008 and Feb 2010. Everolimus, 10 mg daily, was given until disease progression or unacceptable toxicity. Primary objective was to determine 4-month progression-free survival (PFS) and secondary objectives were to investigate response rate, toxicity and overall survival OS rate. Pre- (n = 28) and on-treatment (n = 19) tumor biopsies were evaluated for phosphorylated (p) mTOR, pS6 kinase1, pS6 and eukaryotic initiation factor 4E binding protein 1 expression. Results: A total of 180 cycles of everolimus were administered with a median of 2 (range, 1-20) cycles in each patient. Two patients (3.7%) achieved confirmed partial response and 19 patients (35.2%) showed stable disease, resulting in a disease control rate of 38.9%. At a median follow-up duration of 8.7 months in surviving patients (range, 3.0–19.4 months), a 4-month PFS rate was 18.4% with a median PFS of 1.7 months (95% CI, 1.5-2.2 months) and a median OS time was 8.3 months (95% CI, 4.5-12.1 months). Peritoneal metastasis (Hazard ratio [HR], 3.97; 95% CI, 1.54-10.23; p = 0.010) and low expression level of pS6Ser240/4 at baseline (HR, 7.64; 95% CI, 2.591-22.51; p = 0.001) were significantly associated with shorter PFS time. Treatment was in general well tolerated. Toxicities of grade 3/4 included anemia (9.4%), thrombocytopenia (9.4%), hepatic dysfunction (11.3%) and pulmonary toxicities (one interstitial pneumonitis and a diffuse alveolar hemorrhage [DAH] case). The DAH and cardiopulmonary dysfunction in another case resulted in treatment-related mortalities. Conclusions: Everolimus monotherapy showed modest activity against AGC refractory to FP. pS6Ser240/4 might be a potential biomarker for the clinical activity of everolimus. The toxicity profile was generally mild. However, careful monitoring for treatment-related pulmonary complication seems to be required. [Table: see text]
A meta-analysis comparing positive surgical margin and complication rates of 110,016 patients undergoing open retropubic, laparoscopic, and robotic-assisted radical prostatectomy.
Authors: Sooriakumaran P. , Bloch D. , Hebert A. , Seshadri-Kreaden U. , Wiklund P. , Tewari A. 
Published: February 2017

103 Background: There is no clear evidence to support one form of surgical approach over another with regards radical prostatectomy. The aim of this study was to analyze the literature available between 2002 and 2008 and compare positive surgical margin and complication rates for open retropubic, laparoscopic, and robotic radical prostatectomy. Methods: A total of 110,016 patients formed the basis of this meta-analysis, representing the largest compilation of radical prostatectomy patients in the literature. Summary data were abstracted on year of publication, pre-operative patient characteristics, positive surgical margins, estimated blood loss, blood transfusions, conversions, length of hospital stay, and total intra- and peri-operative complications, with a further 21 individual perioperative complications selected a priori for abstraction and analysis. Results: The open and laparoscopic surgical groups had similar overall positive surgical margin rates, with the robotic group having lower rates. Both minimally invasive approaches showed significantly lower estimated blood loss and rate of blood transfusions, and a shorter length of hospital stay when compared to an open approach. A further decrease in these parameters was seen when robotic assistance was used. Total complication rates were highest for the open approach, intermediate for the laparoscopic cohort, and lowest for the robotic group. For the individual complication analysis, the rates for death, readmission, reoperation, ureteral, bladder, and rectal injury, ileus, pneumonia, fistula, and wound infection showed significant differences between groups. Conclusions: Robotic assisted laparoscopic radical prostatectomy has overall lower perioperative morbidity and improved early oncologic outcomes compared to conventional laparoscopic or open approaches. Further studies comparing longer term oncologic and functional outcomes, as well as cost-benefit comparisons are needed before making recommendations for or against a specific type of surgery. [Table: see text]
A review of radical prostatectomy outcomes in active surveillance patients—The Sunnybrook experience.
Authors: Jethava V. , Vesprini D. , Loblaw D. A. , Mamedov A. , Nam R. , Klotz L. 
Published: February 2017

104 Background: Prostate cancer is the most prevalent non-cutaneous cancer among North American men. Approximately 50% of these are favorable risk cancers; the NCCN guideline recommends active surveillance for these patients. Patients are generally followed by serial PSAs, DREs and/or TRUS-guided biopsies with triggers identified for each test. Consequently, about 30% of these cancers will be reclassified to a higher risk and require definitive treatment. Cases treated with radical prostatectomy (rP) give important insights into the biology of these cancers. Methods: The ASURE database of active surveillance patients was used to identify cases; a retrospective chart review was completed. The following variables were extracted: primary reason for rP; % biochemical failure; % of patients requiring salvage radiation or hormone therapy; Gleason score (GS), tumor size staging and nodal status in the rP specimen; cause and rate of mortality; proportion of patients treated for PSA-doubling times less then 3 years presenting with a GS greater than 7. Descriptive statistics were used to summarize the results. Results: Of 566 patients in the ASURE database, the charts of 26 patients having an rP were extracted. The primary cause for an rP was a PSA-doubling times less than 3 years (57% of patients) followed by a biopsy indicating a GS of 4+3 or greater (19%). 7% of patients (2/26) were not reclassified but preferred to be treated with rP. 4 patients had biochemical failure (15%) all 4 had salvage therapy. There was 1 cause-specific death. 85% of rP specimens had GS 7, while the remaining had GS 6. Half of these GS 7 individuals had PSA doubling times of less than 3 years. Conclusions: Radical prostatectomy appears to be an effective deferred treatment for patients who are reclassified on active surveillance as evidenced by low prostate-cancer mortality, low rates of biochemical failure acceptable use of salvage therapy. Of interest is that the majority patients with PSAdt < 3 y have Gleason 7 disease on specimen. No significant financial relationships to disclose.
Pathologic outcomes in patients with clinically low-risk prostate cancer deemed eligible for active surveillance.
Authors: Srivastava A. , Grover S. , Sooriakumaran P. , Rajan S. , El-Douaihy Y. , Tewari A. 
Published: February 2017

110 Background: Active surveillance (AS) is becoming increasingly popular as a treatment option for men with clinically localized low-risk prostate cancer. Gleason score ≤ 6 and clinical stage ≤ T2a are selection criteria for AS. However, Gleason upgrading or upstaging from the diagnostic biopsy to the surgical specimen is not uncommon. We thus sought to identify risk factors that could more accurately predict Gleason upgrading and/or upstaging in AS-eligible men. Methods: 786 patients from our prospective database of 2,412 men who underwent robotic-assisted radical prostatectomy by a single surgeon from January 2005 to August 2010 would have fulfilled standard AS criteria (Gleason sum ≤ 6, clinical stage ≤T2a disease, PSA <10ng/ml, <3 positive cores and ≤50% cancer present in a single core). This formed the basis of our study cohort. Clinicopathologic parameters, including number of cores at initial biopsy, biopsy cancer volume, preoperative PSA, number of cancer-positive cores, body mass index, and prostate volume were recorded prospectively. Data were evaluated using chi- square and multivariate logistic regression analyses. Receiver operator characteristic curves (ROC) were constructed to determine the optimal cutoff values. Results: 320 of 786 AS-eligible patients (40.7%) had Gleason upgrading at final pathology following radical prostatectomy. Upstaging was present in 591 patients (75.1%). 626 patients (79.6%) had Gleason upgrading and/or upstaging. On univariate analysis, BMI, PSA density, preoperative PSA, lower prostate volume and maximum percentage of cancer in biopsy cores were predictors of Gleason upgrading and/or upstaging. On multivariate analysis, all variables, except for BMI and PSA density, lost statistical significance. PSA density > 0.1 ng/ml/cm3 and BMI >29 kg/m2 are the optimal cutoff values based on ROC analysis. Conclusions: PSA density and BMI are significant predictors of Gleason upgrading and/or upstaging, and should be incorporated into contemporary selection criteria for AS protocols. No significant financial relationships to disclose.
Robotic-assisted radical prostatectomy in a system of universal health care with limited access to high-tech resources.
Authors: Autran Gomez A. , Alzaharani A. , Williams A. , Chin J. 
Published: February 2017

116 Background: The goal of radical prostatectomy (RP) is to minimize the positive surgical margin (PSM) rate. Robotic- assisted radical prostatectomy (RALP) has the theoretical advantages of enhanced ability to identify surgical dissection planes to improve surgical outcome but is associated with a learning curve. The objective is to review the PSM rate and intra- and postoperative complications (Clavien grading) correlating with possible risk factors in a low-density RALP by a high-volume, open RP surgeon working in the Canadian Healthcare System. Methods: The data of 56 RALP from April 2004 to Dec 2009 by one surgeon contemporaneously performed 830 RP. PSM was analyzed and correlated with clinical variables. Univariable and multivariable analyses were used. Results: PSM 19 (34%) cases. At univariable analysis, no association was observed between PSM and age BMI, PSA, number positive cores, % positive cores, Gleason biopsy and clinical stage. Pathological Gleason (p=0.012), pathological stage (p= 0.003) and % tumor in surgical specimen (p=<0.001) were associated with increased risk of PSM. At multivariable the % tumor in surgical specimen (p<0.001) were only independent predictive factor for PSM. According to localization of PSM Apical 9 (48%), PLR 4 (21%), PLL 4 (21%) and bladder neck 1 (5%). Mean follow-up 23 months. In PSM, 12 (63%) showed an undetectable PSA (≤0.01ng/mL) at 3 months. Using Clavien grading, 9 surgical complication in 9(16%) patients: 6 (grade 1–2) and 3 (grade 3–4). 4 patients with PSM had complications, 2 (grade1-2) and 2 (grade 3–4). At multivariable analyses, BMI (p=0.008) was the only predictive factor for occurrence of complications. Conclusions: The pathological stage and tumor (%) in the surgical specimen were independent predictive factor for PMS. Applying the Clavien grading, most of the patients presented minor complications. The Canadian Universal Healthcare system with limited access to high-tech resources may not be ideal for introducing an expensive new surgical technique, especially for an ubiquitous procedure such as RP. However, results of our low-density series or sporadic cases were not inferior to reported initial experience series of RALP in the literature. No significant financial relationships to disclose.
Association between radiographic response and overall survival in men with metastatic castration-resistant prostate cancer receiving chemotherapy.
Authors: Sonpavde G. , Pond G. R. , Berry W. R. , De Wit R. , Eisenberger M. A. , Tannock I. , Armstrong A. J. 
Published: February 2017

118 Background: In men with metastatic castration resistant prostate cancer (CRPC),the association of measurable tumor responses with overall survival (OS) is unknown. We retrospectively evaluated the TAX327 phase III trial to study this relationship. Methods: Eligible patients for this analysis included those with WHO-defined measurable metastatic disease randomized to receive either docetaxel or mitoxantrone. OS was estimated using the Kaplan-Meier method and the prognostic relationship of WHO-defined radiologic response with OS was performed using Cox proportional hazards regression. Landmark analyses evaluated survival from baseline and 2, 3, 4 and 6 months after baseline. Results: Four hundred and twelve patients enrolled on the TAX327 trial had measurable tumors. Thirty-seven patients exhibited a complete or partial objective response (CR/PR, 9.0%), 116 had stable disease (SD, 28.2%), 99 had progressive disease (PD,24%) and 160 (38.8%) did not have a post-baseline objective assessment. Partial responders demonstrated longer median OS (29.0 months) than patients with SD (22.1 months), or those with PD (10.8 months) or those who were not assessed (12.7 months). These results remained after landmark analysis. We found a significant association between ≥30% PSA declines and radiologic response, with ≥30% PSA declines occurring in all patients with CR/PR, 79.8% of patients with SD and 34.4% with PD. Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain-response and ≥30% PSA-decline (p=0.009). Conclusions: In men with metastatic CRPC and measurable disease receiving chemotherapy, objective tumor response was prognostic for OS, and appears to complement PSA assessment. [Table: see text]
Phase I trial of anti-PSMA designer T cells in advanced prostate cancer.
Authors: Junghans R. P. , Rathore R. , Ma Q. , Davies R. , Bais A. , Gomes E. , Beaudoin E. , Davol P. , Abedi M. , Cohen S. 
Published: February 2017

130 Background: We created chimeric immunoglobulin-T cell receptors (IgTCR) specific for prostate specific membrane antigen (PSMA). When expressed in patient T cells, these “designer T cells” (dTc) specifically kill prostate cancer cells in vitro and in vivo in animal models, with 5/9 (55%) of xenografted mice experiencing complete remissions (Ma et al. Prostate 2004:61:12–25). A phase I clinical trial was approved by the FDA. Methods: Patient T cells are retrovirally transduced and expanded ex vivo to span dose levels of 10^9 to 10^11 T cells. Patients undergo prior non-myeloablative (NMA) conditioning to create “hematologic space” into which designer T cells are infused for stable engraftment and prolonged in vivo efficacy. Patients are co-administered continuous infusion IL2. Outcomes include Phase Ia goals of safety and Phase Ib goals of establishing an optimal biologic dose in terms of designer T cell engraftment. Results: Five patients have been treated, three at 10^9 and two at 10^10 cell dose levels. Excellent T cell modifications of 30%-60% were obtained. After NMA conditioning, T cells were infused. Stable engraftments of 1%-20% post-recovery at one month after T cell infusion, thus affirming one of the study end-points. Patients experienced neutropenic fever after conditioning, but no designer T cell-related toxicities. Two patients had partial responses with PSA reductions of 50 and 70% in the two months following treatment with projected benefits of 4 months gain of time to return to starting PSA levels. Results will be updated at the conference. Conclusions: A new approach to adoptive immune therapy in metastatic prostate cancer has been devised with encouraging early results. Patients are being actively recruited. This clinical trial received partial funding from the US Army/DOD. Preclinical work was supported by the Prostate Cancer Foundation. No significant financial relationships to disclose.
Results of a phase I/II clinical trial of BPX-101, a novel drug-activated dendritic cell (DC) vaccine for metastatic castration-resistant prostate cancer (mCRPC).
Authors: Sonpavde G. , McMannis J. D. , Bai Y. , Seethammagari M. , Bull J. M. , Hawkins V. , Dancsak T. , Lapteva N. , Spencer D. M. , Slawin K. M. 
Published: February 2017

132 Background: We report results of a phase I/II clinical trial of BPX-101, a drug- activated autologous DC vaccine targeting PSMA. Methods: Men with progressive mCRPC following up to one prior chemotherapy regimen were enrolled in a 3+3 dose escalation trial evaluating BPX-101 and CD40 activating agent AP1903. BPX-101 was administered intradermally every 2 weeks for 6 doses, during the induction phase, and for nonprogressing patients, every 8 weeks for up to 5 doses during the maintenance phase. AP1903 (0.4 mg/kg) was infused 24 hours after each BPX-101 dose. Radiologic evaluation was performed every 12 weeks. Results: Planned enrollment of 12 subjects has been completed, including 3 each at 4 × 106 and 12.5 × 106 cells/dose, and 6 at 25 × 106 cells/dose. All vaccine products were releasable. Median Halabi- predicted survival was 13.8 months. Two subjects went off protocol prior to the end of induction due to progression, 8 reached end of induction, and 2 are nearing completion of induction. Toxicities (e.g. injection site reactions) were generally mild. One high dose subject experienced a single acute cytokine reaction during infusion of AP1903 at the second vaccination, but continued induction without further drug-related adverse events. Notably, one post- docetaxel subject in the low dose cohort achieved a RECIST PR, and one chemo-naive subject in the mid-dose cohort with extensive visceral, nodal, and bone metastases experienced a RECIST CR with docetaxel-based chemotherapy after induction and maintains an undetectable ultrasensitive PSA (0.009 ng/mL) 10 months after enrollment. A third subject, in the high-dose cohort, experienced near complete elimination of multiple lung metastases with otherwise stable disease by the end of induction. Robust immune responses were seen in all three. Conclusions: BPX-101 can be reliably manufactured and safely administered, followed by AP1903, at doses of at least 25 × 106 cells. Contrary to the observation that cancer vaccine therapy improves survival without short-term response, BPX-101-treated patients have experienced measurable disease responses, including near elimination of poor-risk visceral disease. [Table: see text]
Effect of G-CSF prophylaxis on the occurrence of neutropenia in men receiving cabazitaxel plus prednisone for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in the TROPIC study.
Authors: Ozguroglu M. , Oudard S. , Sartor A. O. , Hansen S. , Machiels J. H. , Shen L. , De Bono J. S. ,   for the TROPIC Investigators
Published: February 2017

144^ Background: The phase III TROPIC study showed that cabazitaxel plus prednisone (CbzP) improves survival compared with mitoxantrone plus prednisone (MP) in men with mCRPC who progressed after docetaxel-based therapy (HR 0.70; p<0.001; Lancet 2010;376:1147). In this study, a higher percentage of men in the CbzP group had grade ≥3 neutropenia (81.7% versus 58.0%). We analyzed the effect of G-CSF use on the occurrence of grade ≥3 neutropenia. Methods: 755 men with mCRPC who progressed during or after a docetaxel-containing regimen were randomized to receive 10 mg of oral prednisone daily and either 12 mg/m2 of mitoxantrone or 25 mg/m2 of cabazitaxel every 3 weeks. Primary prophylaxis with G-CSF was not permitted at cycle 1, but was allowed after the first occurrence of neutropenia either lasting ≥7 days or complicated by fever >38.5°C, or fever >38.1°C for three observations during a 24- hour period, or infection. We analyzed the effect of G-CSF use on the occurrence of neutropenia in cycles 2–10. G-CSF use was defined as either prophylactic (administered within 3 days of chemotherapy dose) or therapeutic (administered more than 3 days after chemotherapy dose). Results: A total of3246 cycles (1881 CbzP; 1365 MP) were administered from cycle 2 onward. No G-CSF was used in 2,322 cycles (1144 CbzP; 1178 MP) and the percentage of these cycles with grade ≥3 neutropenia was similar between the groups (44.6% CbzP; 38.4% MP). G-CSF was used in more cycles in the CbzP group as prophylaxis (588 CbzP; 118 MP; chi-square P<0.0001) and therapeutically (149 CbzP; 69 MP; P=0.0013). The percentage of CbzP cycles with grade ≥3 neutropenia was lower when G-CSF was used early as prophylaxis versus using it later as a therapeutic modality (24.7% versus 57.7%; P<0.0001). A reduction in grade ≥3 neutropenia favoring prophylactic versus therapeutic G-CSF was also observed in the MP group (9.3% versus 33.3%; P<0.0001). Conclusions: The appropriate and timely use of G-CSF as prophylaxis reduces the occurrence of neutropenia in men receiving CbzP for mCRPC. Adherence to current guidelines on the use of G-CSF is recommended to manage this predictable side effect. [Table: see text]