tbuckley/cabot-search huggingface dataset:
How does stereotactic body radiotherapy compare to standard external beam radiotherapy or low-dose rate brachytherapy for low-risk prostate cancer?
Authors: Perakaa Sethukavalan, Patrick Cheung, Gerard Morton, Laura D'Alimonte, Andrea Deabreu, Alexandre Mamedov, Liying Zhang, Hans T. Chung, Robert Nam, D. Andrew Loblaw
Journal: Journal of Clinical Oncology (2013)

e16070 Background: Stereotactic body radiotherapy (SBRT) is an emerging radiotherapy technique that appears to be efficacious, well tolerated and convenient. However, outcomes for patients treated with SBRT are unknown compared to more conventional radiation options for patients with prostate cancer. The purpose of this study is to evaluate and compare late toxicities and biochemical disease-free survival (bDFS) of low risk prostate cancer patients treated SBRT (35Gy/5 fractions), standard external beam radiotherapy (STND; median 76Gy/38 fractions) or low-dose brachytherapy (LDR; iodine-125, 145Gy) at the Odette Cancer Centre. Methods: Consecutive patients with low risk prostate cancer treated with radiation from 2006-2008 were analyzed. Patients treated with SBRT were part of a phase 2 prospective clinical trial; patients treated with STND or LDR had data abstracted from medical charts retrospectively. Patients treated with neoadjuvant androgen deprivation therapy were excluded from biochemical analyses. Univariate (UVA) and multivariate analyses (MVA) of Cox proportional hazard model were conducted to identify significant covariates predicting bDFS. Results: A total of 357 low-risk prostate cancer patients were identified (84 SBRT, 81 STND and 192 LDR). The median follow-up was 57, 62, and 59 months, respectively. At baseline, 85% of patients were T1c, 15% T2a; 100% had GS 6; median PSA 5.9 ng/ml. There were more patients in the STND and LDR cohort who had T2a disease (6%, 21% and 16%, p= 0.013) and the mean PSA was higher in the STND cohort (6.08, 6.69, and 6.02, p=0.017). Patients who received LDR experienced more late hematuria (0%, 1.23% and 11.98%, p&lt;0.0001); otherwise there were no significant differences in late toxicities observed. There were no significant differences in bDFS (97.4% vs 96.9% vs 97.2% at 60 months, p=0.94). There were no covariates identified predicting bDFS on UVA or MVA, including treatment type. Conclusions: SBRT, STND and LDR show equivalent effectiveness and both external beam techniques showed less hematuria than LDR. However, SBRT and LDR are more convenient and less costly than STND. Further prospective studies of SBRT are ongoing.
Postoperative morbidity and mortality in a large series of primary retroperitoneal sarcoma (RPS) treated at 8 tertiary centers: A study from the Transatlantic RPS Working Group.
Authors: Dirk C Strauss, Dario Callegaro, Sylvie Bonvalot, Rosalba Miceli, Carol Jane Swallow, Peter Hohenberger, Frits van Coevorden, Rick L. M. Haas, Piotr Rutkowski, Raphael E. Pollock, Marco Fiore, Andrew J Hayes, Mark Fairweather, Chandrajit P. Raut, Alessandro Gronchi
Journal: Journal of Clinical Oncology (2015)

10557 Background: To explore postoperative morbidity and mortality of patients (pts) with primary retroperitoneal sarcoma (RPS) undergoing surgery at 8 high volume centers (the Transatlantic RPS working group). Methods: All consecutive pts with primary RPS treated at 2 North American and 6 European centers between 2002 and 2011 were included in a retrospective analysis. Postoperative adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) and mortality at 30, 60 and 90 days were analyzed. Overall survival (OS), local recurrence (LR) and distant metastasis (DM) calculated. Multivariate analysis performed exploring risk factors for postoperative complications considering age, size, number and type of resected organs, preoperative chemotherapy and radiotherapy. Results: Total of 1007 pts were included in the database. Median follow-up was 58 months (range 36-90mo). Five and 10yr OS, LR and DM were 67% and 46%, 26% and 35%, 21% and 22% respectively. Postoperative complications of CTCAE grade ≥ 3 were observed in 207 pts (21%); grade 3 complications in 128 pts (12.7%), grade 4 in 52 pts (5.2%) and grade 5 for 19 pts (1.9%). The postoperative complication rate varied from 14.4 to 37.0% among centers. The re-operation rate was 10.5%. Most common complications were postoperative bleeding/hematoma (3.0%), bowel anastomotic leak/fistula (2.6%) and bowel obstruction/ileus (2.3%). The 30, 60 and 90-day mortality rate were 1.8 (95% CI 1-2.6), 2.9 (95% CI 1.8-3.9) and 4.1% (95% CI 2.9-5.3) respectively. In multivariable analysis, the occurrence of a postoperative complication was significantly associated with worst OS (HR 1.54, 95% CI 1.08-2.19, p = 0.016) and higher LR rate (HR 1.59, 95% CI 1.09-2.30, p = 0.015) while it was not significantly associated with a worst DM rate (HR 1.33, 95% CI 0.90-1.98, p = 0.153). Conclusions: Data about short-term morbidity are consistent with previous studies on RPS and comparable to those other major abdominal cancer surgery. The balance between the expected morbidity and the possible improvement in oncologic outcome should be factored in the management algorithm and tailored to the patient.
Clinical benefit from pemetrexed before and after crizotinib exposure in patients with ALK positive non-small cell lung cancer (ALK+ NSCLC).
Authors: Eamon Berge, Maxon Delee, Xian Lu, Anna E. Barón, Benjamin J. Solomon, Robert Charles Doebele, D Ross Camidge
Journal: Journal of Clinical Oncology (2012)

7601 Background: Crizotinib (Criz) produces high response rates and prolonged progression free survival (PFS) in ALK+ NSCLC. Retrospective analyses suggest enhanced sensitivity to pemetrexed (Pem) in Criz-naïve ALK+ NSCLC. Different biological mechanisms of Criz resistance have recently been discovered. Clinical cross-resistance between Criz and Pem has not been previously investigated. Methods: Patients with stage IV ALK+ NSCLC treated in sequence with Pem then Criz (Pem-Criz), or Criz then Pem (Criz-Pem) were identified. Excluding CNS only progression events when no new systemic treated was started, PFS was compared using Cox Proportional Hazards. Correlations between molecular features of ALK positivity and Pem PFS were analyzed using Spearman correlations. Treatment sequence effect was explored using Fisher’s exact test. Results: We identified 19 Pem-Criz and 9 Criz-Pem ALK+ patients. Pem was given as monotherapy in 37% vs. 66%, and as median 2nd vs. 3rd line cytotoxic in the Pem-Criz and Criz-Pem groups, respectively. For the Pem-Criz group,median PFS was 8.9 months with Pem (range: 1-21.5 months), and 14.7 months with Criz (range:2.9+ -27.5 months). For the Criz-Pem group, median PFS was 8.4 months with Criz (range: 2-29 months), and 4.4 months with Pem (range: 0.5-10.5+ months). Patients were more likely to progress on Pem given after Criz than before, but confidence intervals were wide (HR 1.51, 95% CI 0.626-3.66). Neither native or rearranged signal copy number, nor percent cells ALK+ in the tumors correlated with PFS on Pem. Conclusions: Both Criz and Pem appear to be active drugs in ALK+NSCLC given in either order. Numerically, benefit from Pem was less when given post-Criz compared to pre-Criz, however this difference was not statistically significant. Several potential confounders exist in our small dataset (notably differences in line of therapy and use in combo vs. monotherapy). To fully address whether there may be a significant difference in overlap of induced specific drug resistance mechanisms, the clinical effect of Criz/Pem sequencing should be explored in a larger series adjusting for confounding effects.
Hydration with magnesium and mannitol without furosemide prevents the nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced non-small cell lung cancer.
Authors: Keiko Muraki, Ryo Koyama, Kentaro Suina, Tetsuhiko Asao, Yuichiro Honma, Takehito Shukuya, Rina Ohashi, Naoko Shimada, Fumiyuki Takahashi, Kazuhisa Takahashi
Journal: Journal of Clinical Oncology (2013)

e19043 Background: The aim of this study was to examine the effect of hydration with magnesium and mannitol without furosemide on the nephrotoxocity accompanying combination chemotherapy using cisplatin and pemetrexed in patients with advanced non-small cell lung cancer (NSCLC). Methods: Fifty patients with NSCLC who received cisplatin plus pemetrexed, using either old hydration protocol including normal saline with mannitol and furosemide, or a new one including normal saline with magnesium and mannitol without furosemide were retrospectively analyzed. Nephrotoxicity was compared between patients treated using the old protocol and those treated with the new protocol. Univariate and multivariate analyses were performed to identify the independent factors associated with protection against nephrotoxicity in patients with NSCLC who received cisplatin plus pemetrexed. Results: Thirty patients received the old hydration protocol, while 20 patients were treated using the new hydration protocol. The patients treated using the new hydration protocol showed a significantly greater increase in creatinine clearance (p=0.0004) and a decrease in the serum creatinine level (p=0.0148) after one course of chemotherapy compared with those treated using the old hydration protocol. There were no differences in the chemotherapeutic response or overall survival between the groups (p=0.572). The new hydration protocol with supplemented magnesium with mannitol without furosemide was an independent factor for the protection against nephrotoxicity induced by cisplatin and pemetrexed in patients with advanced NSCLC (HR 0.232 (95% CI: 0.055-0.986), p=0.039). Conclusions: These results demonstrate that the new hydration protocol comprising supplementation with magnesium without furosemide could prevent the nephrotoxicity induced by cisplatin and pemetrexed without affecting the treatment outcome.
CEA levels and EGFR mutations associated with patients in nonsmokers lung cancer.
Authors: Baohui Han, Yu Dong, Yanwei Zhang, Bo Jin
Journal: Journal of Clinical Oncology (2012)

e18038 Background: Background: As the non-smoking Asian patients with adenocarcinoma of the EGFR gene tend to have higher mutation rate, and serum CEA levels in patients with lung cancer, especially adenocarcinoma, high expression in many recent years, studies have also found that serum CEA levels in EGFR-changes before and after TKI therapy efficacy and treatment are closely related. However, whether serum CEA level and EGFR gene mutations is a correlation between two biomarkers. This study attempts to explore its relevance between EGFR gene mutations and analysis of serum CEA levels in non-smoking patients with lung cancer and it’s various clinical and pathological features. Methods: 84 cases of histologically confirmed non-smoking history in newly diagnosed lung cancer patients, respectively, serum CEA levels and histological detection of EGFR gene. According to the expression level of serum CEA patients were divided into high expression and did not express two groups were compared in patients with EGFR gene mutations. Results: 58/84 cases were found with activity EGFR gene mutations, the overall mutation rate was 69.0%, serum CEA levels high expression of EGFR gene mutation was significantly higher than non-expression group (serum CEA levels were &lt;5ng/ml, ≥ 5ng/ml &lt;20ng/ml, ≥ 20ng/ml patients with EGFR gene mutations histology were 63.2%, 70.8%, 81.8%). Conclusions: Non-smoking lung cancer patients with serum CEA levels and EGFR gene mutations was positively correlated.
The relationship between tumor expression of phosphorylated STAT3 and pathology and outcome in colorectal cancer.
Authors: Graeme JK Guthrie, Jonathan J Platt, Zahra MA Mohammed, Campbell SD Roxburgh, Paul G Horgan, Donald C. Mcmillan, Joanne E. Edwards
Journal: Journal of Clinical Oncology (2012)

e14054 Background: Cancer-associated inflammation has recently been identified as a key determinant of disease progression and survival in colorectal cancer(CRC). The signal transducer and activator of transcription 3(STAT3) pathway is central to the inflammatory response, and has been implicated in cancer development and progression. This study aimed to evaluate tissue expression of cytoplasmic and nuclear STAT3 expression in CRC and its association with clinicopathological variables and survival. Methods: Patients were identified from a prospectively maintained CRC database. Using immunohistochemistry on a tissue microarray, cytoplasmic and nuclear expression of phosphorylated STAT3 (p-STAT3) at both the tyrosine 705(tyr705) and serine 727(ser727) phosphorylation sites was assessed using the weighted histoscore. Associations between p-STAT3 expression and clinicopathological factors and survival were examined. Results: In 273 patients, cytoplasmic and nuclear p-STAT3 expression was examined and considered positive if staining was observed in more than 15% of tumour cells. When colonic and rectal tumours were considered together, cytoplasmic and nuclear p-STAT3 expression at both phosphorylation sites (tyr705 and ser727) showed no significant relationship with clinicopathological variables. Similarly, when colonic tumours were considered alone, cytoplasmic and nuclear p-STAT3 expression showed no association with clinicopathological factors. In rectal cancer, although cytoplasmic p-STAT3 was not significantly associated with survival, nuclear p-STAT3 expression was associated with improved survival(tyr705 p=0.007, ser727 p=0.098). Similar to the colon cancer group, rectal cancer nuclear p-STAT3 expression showed no correlation with clinicopathological variables. Conclusions: Tumour nuclear p-STAT3 expression and its association with outcome appears to depend on tumour site with improved survival associated with nuclear p-STAT3(tyr705) expression in rectal but not colon cancer. The basis of this observation is not clear and further assessment of the role of p-STAT3 in the tumour microenvironment is required.
Clinical outcomes of positive resection margins after endoscopic resection of early colorectal cancer.
Authors: Jin-Oh Kim
Journal: Journal of Clinical Oncology (2017)

688 Background: The management of patients with a positive resection margin after endoscopic resection of early colorectal cancer (ECC) depends on various clinical factors, including the pathology. There is little information on the clinical outcomes according to the subsequent management of a positive resection margin in patients with ECC treated by endoscopic resection. We assessed the management according to the pathology of the positive margin and evaluated the clinical outcomes. Methods: Consecutive patients with ECC who underwent endoscopic resection from January 2004 to December 2014 were reviewed. This study retrospectively analyzed 363 lesions from 338 patients (mean age, 60.1 years; 68% [230/338] male). Results: The resection margin was positive in 29.2% of patients, including cancer cells in 9.9%, adenoma in 16.5%, and high-grade dysplasia (HGD) in 2.8%. Subsequent surgery was performed on 11.8% of patients, 72.2% (26/43) of whom were cancer cell–positive, while 23.3% (10/43) were resection margin–negative but had deep submucosal (SM) or lymphatic invasion. Remnant cancer cells were identified in 25.6% (11/43) of the operated group and 81.8% (9/11) of the cancer cell–positive group. On early follow-up surveillance colonoscopy (mean interval, 3.57 months) in 88.2% of patients (320/363), including 95.7% (67/70) of the adenoma and HGD-positive group, only one (0.3%, 1/320) case of remnant adenoma was found. In the multivariate analysis, deep SM invasion ( p=0.026), number of pieces of piecemeal resection (p=0.03) and cancer cell positivity ( p=0.001) predicted subsequent surgery. In the multivariate analysis, an endoscopic appearance of incomplete resection ( p=0.002) and cancer cell positivity (p=0.041) were related to the identification of remnant cancer cells after subsequent surgery. Conclusions: Patients with an adenoma-positive resection margin had favorable clinical outcomes during subsequent surveillance. The choice of subsequent surgery was related to deep SM invasion and cancer cell–positive resection margins, and subsequent surgery group showed a high rate of remnant cancer cells.
Safety and efficacy of <sup>177</sup>lu-PSMA-617 radioligand therapy in patients with mCRPC: A multicenter study.
Authors: Kambiz Rahbar, Hojjat Ahmadzadehfar, Clemens Kratochwil, Richard P. Baum, Matthias Schmidt, Andreas Pfestroff, Vikas Prasad, Aelxander Heinzel, Juri Ruf, Maria Eveslage, Martin Boegemann, Wolfgang Fendler, Bernd J Krause
Journal: Journal of Clinical Oncology (2017)

155 Background: Prostate specific membrane antigen (PSMA) is a promising target for imaging and therapy of prostate cancer. Small cohorts trials have shown promising results for response and tolerability of 177 Lu-PSMA-617 radioligand therapy (RLT) in patients with metastatic castration-resistant disease. The aim of this multicenter study was to investigate safety and efficacy of this new therapy in a large, multicenter cohort. Methods: Data of 145 patients with metastatic castration resistant prostate cancer treated with at least a single dose of 177 Lu-PSMA-617 at 12 therapy centers in Germany (median age 73 years, range 43-88) were collected. Up to 4 therapy cycles (range of administered activity 2 – 8 GBq) were given. Toxicity was categorized by the common toxicity criteria for adverse events based on serial blood tests and the physician’s report. Biochemical response was defined by a PSA decline ≥ 50% from baseline. Results: 248 therapy cycles were performed. Data for biochemical response were available in 99 patients and data for physician-reported and lab-based toxicity in 145 and 121 patients. The median follow-up was 16 weeks (range 2-30 weeks). Nineteen patients died during the observation period. Grade 3 to 4 hematotoxicity occurred in 18 patients: 10%, 4% and 3% of the patients experienced anemia, thrombocytopenia and leukopenia, respectively. Xerostomia occurred in 8%. Overall biochemical response rate was 45% following all therapy cycles. Elevated alkaline phosphatase and presence of visceral metastases were negatively correlated and the total number of therapy cycles correlated positively with biochemical response. 22 of 31 patients with no PSA decline &gt; 50% after the first cycle did not respond to the second therapy cycle. Conclusions: Radioligand therapy with 177 Lu-PSMA-617 shows promising response rates and a low toxicity in extensively pretreated patients with prostate cancer. Future prospective trials have to evaluate the effect of RLT on survival and potentially be considered in earlier stages of prostate cancer.
A multicenter phase II study of bendamustine with rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).
Authors: Michinori Ogura, Kiyoshi Ando, Nozomi Niitsu, Seok Jin Kim, Ken Ohmachi, Naoki Takahashi, Toshiki Uchida, Naoto Takahashi, Naokuni Uike, Hyeon Seok Eom, Yee Soo Chae, Takashi Terauchi, Ukihide Tateishi, Mitsuaki Tatsumi, Won Seog Kim, Cheolwon Suh, Kensei Tobinai
Journal: Journal of Clinical Oncology (2012)

8023 Background: Effective salvage therapies are needed in patients (pts) with relapsed/refractory DLBCL after R-CHOP. Therapy with bendamustine plus rituximab (B-R) was well tolerated and effective in the preceding phase I study in relapsed/refractory aggressive B-cell non-Hodgkin lymphoma, including DLBCL. This phase II study assessed the efficacy and safety of B-R in pts with relapsed/refractory DLBCL. Methods: Pts with histologically confirmed DLBCL (excluding transformed disease) and 1-3 prior therapies received rituximab 375 mg/m 2 IV on day 1 and bendamustine 120 mg/m 2 IV on days 2 and 3 of each 21-day cycle, for up to 6 cycles. Recovery of neutrophil count to ≥1,000/mm 3 and platelet count to ≥75,000/mm 3 were required prior to the start of each cycle; treatment delays &gt;2 weeks resulted in discontinuation. The primary endpoint was overall response rate (ORR); secondary endpoints included complete response (CR) rate, progression-free survival (PFS), and safety. Results: A total of 63 pts were enrolled; data from 59 pts were available. Median age was 67 (range, 36-75) years with 37 pts over 65 years. The majority of pts (64.4%) had 1 prior therapy; 57 pts (96.6%) were previously treated with rituximab-containing combination chemotherapy and 8 (13.6%) had prior auto-PBSCT. Pts received a median of 4 (range, 1-6) treatment cycles. Sixteen (27.1%) pts completed 6 treatment cycles; most common reasons for early discontinuation were disease progression (n=15) and failure to meet criteria to start the next cycle (n=13). Among 59 pts evaluable for response, ORR was 62.7% with a 37.3% CR rate. The median PFS was 200 days (95% CI, 109-410). Most common grade 3/4 adverse events (AEs) included CD4 lymphocytes decreased (66.1%), neutropenia (54.2%), and thrombocytopenia (10.2%). Four (6.8%) pts discontinued due to serious AEs (cytomegalovirus infection, infection, pneumonia, and pneumonia/respiratory failure). Conclusions: B-R demonstrated promising activity in pts with relapsed/refractory DLBCL. Toxicity was primarily hematologic and generally manageable. These results suggest that B-R is a promising salvage regimen for pts with relapsed/refractory DLBCL after R-CHOP.
Study of the gastroenteropancreatic neuroendocrine tumor (gep-net) microenvironment beyond angiogenesis: The role of lysyl oxidase-like 2 (LOXL2).
Authors: Jorge Barriuso, Elsa Bernal, Laura Guerra Pastrian, Enrique Grande, Daniel E. Castellano, Jaume Capdevila, Cristina Alvarez-Escola, Jaime Martinez, Esther Diaz, Victoria Heredia, Jose Castell, Jaime Feliu, Emilio Burgos, Marta Mendiola
Journal: Journal of Clinical Oncology (2014)

4109 Background: A better understanding of the tumour microenvironment beyond angiogenesis of this heterogeneous group of malignancies remains a challenge. In this study, we present an exploratory analysis of the microenvironment protein expression and its relation with prognosis and previously described biomarkers. Methods: Formalin-fixed and paraffin embedded samples (FFPEs) of patients (pts) who underwent surgery for gep-net and their clinical data were collected consecutively from 1980 to 2012.Tissue microarrays were constructed from non-necrotic areas of tumour foci. Microenvironment related proteins (LOXL2, LOX, CXCR4, TWIST, β-catenin and E-cadherin) were studied by inmunohistochemistry and compared to the expression of SSTR2, ATRX and members of the mTOR pathway. The study was approved by the local Ethic Committee. Univariate (UVA) and multivariate analysis (MVA) was performed. Kaplan- Meier method, log rank test and cox regression was used to study disease free survival (DFS) and overall survival (OS). Results: A total of 115 FFPEswere analysed. Median age was 46 years; female/male ratio 1:1; 78 were intestinal. Grades were: G1 64.3%, G2 11.3%, G3 7 %, unknown 17.4%. Median follow up was 12 years. Stage and grade were statistically significant for DFS and OS (p<0.001) and remain so in the MVA. LOXL2 over expression was associated with better DFS and OS (p<0.001). β-catenin nuclear expression (BCAT) was related to worst DFS and OS (p<0.001). PTEN presence was associated with better DFS (p<0.001). MVA for DFS showed BCAT (p=0.019) and PTEN presence (p=0.024) as independent factors and LOXL2 (p=0.024) and BCAT (p=0.004) were significant for OS after adjustment for stage and grade. LOXL2 expression was associated with SSTR2 (p=0.004). Conclusions: LOXL2 is a druggable novel biomarker candidate for gep-nets. UVA for DFS MVA for DFS UVA for OS MVA for OS LOXL2 0.3 (0.1-0.7) ns 0.2 (0.1-0.5) 0.2 (0.04-0.8) BCAT 9.2 (2.3-37.5) 10.5 (1.5-75.7) 12.8 (3.3-50.5) 11.9 (2.2-65.4) PTEN 0.2 (0.1-0.6) 0.2 (0.04-0.8) ns - LOX 0.3 (0.1-0.7) ns ns - Cox regression for presence vs absence or nuclear localization vs non-nuclear. Hazard ratios and 95%CI. Abbreviations: Ns, non-significant.