tbuckley/cabot-search huggingface dataset:
Advantage of adjuvant radiation therapy in octogenarians undergoing surgical resection of rectal cancer.
Authors: Dhaval Chauhan, Atuhani S. Burnett, Taufiek Konrad Rajab, Marisa Cevasco, Philip Ernst, Donald A. McCain, Suyog A. Mokashi
Journal: Journal of Clinical Oncology (2014)

650 Background: Radiation in patients with rectal cancer is an important adjuvant therapy. It can be given either pre-operative or post-operative phase or both. However the optimum timing of the radiation in terms of pre-operative or post-op phase remains a question of debate in octogenarian patients as there is lack of enough evidence. Methods: In this study we aim to find the optimum time of radiation therapy in octogenarians with rectal cancer undergoing surgical resection. Octogenarians with rectal cancer were selected from surveillance, Epidemiology and End Results (SEER) database collected between 1998 and 2009. The data set contained 4,026 patients with rectal cancer who underwent surgical resection and radiation therapy. They were divided into 3 groups. 1,586 (39%) patients had radiation before the surgery. 66 (2%) patients had radiation before and after the surgery, also called the combination group. 2,347(59%) patients had radiation after the surgery. Taking in the consideration of unequal sample sizes, Tukey-Kramer multiple comparison tests was used to compare the mean survival of the patients in each group. Results: The mean survival in pre-operative radiation group was 37.7 months, in combination group was 48.41 months and post-operative radiation group was 44.3 months. There was no statistically significant difference in survival time between the combination group and the radiation after surgery group (p-value=0.64). There was marginal statistical significance in survival time between the combination group and the before surgery group (p-value=.05). There was a statistically significant difference in survival time between the radiation after surgery group and the radiation before surgery group (p-value&lt;0.0001). Conclusions: Octogenarian patients with rectal cancer undergoing adjuvant radiation therapy, with or without neoadjuvant radiation, have greater survival than compared to neoadjuvant only radiation. There appears to be survival advantage of postoperative radiation therapy in octogenarian patients with rectal cancer.
Formulating a surveillance strategy following surgery for oesophagogastric cancer.
Authors: Sing Yu Moorcraft, Elisa Fontana, David Cunningham, Clare Peckitt, Tom Samuel Waddell, Elizabeth Catherine Smyth, William H. Allum, Jeremy Thompson, Sheela Rao, David Watkins, Naureen Starling, Ian Chau
Journal: Journal of Clinical Oncology (2015)

153 Background: Oesophagogastric adenocarcinoma (OGA) has a poor prognosis, even for patients (pts) with operable disease. We conducted a retrospective study to assess relapse characteristics to see if these could influence follow-up strategies. Methods: We performed a retrospective review of all pts with OGA who had surgery with radical intent at the Royal Marsden between January 2001 – December 2010. Details of first relapse, including date, site, symptoms, method of relapse detection, tumour markers and treatment were recorded. Association of survival outcomes with relapse characteristics was determined by Cox regression univariate analysis. Results: 360 pts with OGA had surgery and 72.8% received neoadjuvant or peri-operative chemotherapy. After a median follow-up of 61.7 months, the median disease-free survival (DFS) was 35.6 months (95% CI 27.0 – 65.4) and median overall survival (OS) was 59.6 months (95% CI 40.7 – 81.2). 147 pts (40.8%) had disease recurrence. 51.0%, 78.9% and 91.8% of relapses occurred within 1, 2 and 3 years respectively. 78.9% of pts had distant relapse only, 7.5% had anastomotic recurrence and 13.6% had both. R1/2 resection was associated with a shorter time to distant relapse (p &lt;0.001) and OS (13.8 months vs 77.7 months, HR 2.76, 95% CI 1.97 – 3.88, p &lt; 0.001). At relapse, 101 pts (68.7%) were symptomatic. The 46 asymptomatic relapses were detected by tumour markers (n = 30, 65.2%), routine CT (n = 10, 21.7%) and endoscopy (n = 3, 6.5%). Symptomatic pts were less likely to receive further treatment than asymptomatic pts (55.5% vs 82.6%, p = 0.001), had worse OS from the time of surgery (18.9 months vs 26.3 months, HR 1.57, 95% CI 1.07 – 2.30, p = 0.02) and worse survival beyond relapse (5.1 months vs 14.6 months, HR 2.05, 95% CI 1.40 – 3.00, p &lt; 0.001). There was no difference in DFS between these two groups (HR 0.90, 95% CI 0.63 – 1.27, p = 0.539), thus excluding a lead time bias. Conclusions: In pts undergoing surgery for localised OGA, over 90% of relapses occurred within the first 3 years. Pts with asymptomatic relapses were more likely to receive further treatment with resultant prolonged OS. A more intensive surveillance program with regular tumour marker measurement should be considered for the first 3 years post surgery.
PAI-1 polymorphism and expression of uPA, PAI-1 and COX-2 in breast cancer
Authors: A. M. Minisini, C. Di Loreto, M. Pestrin, D. Fabbro, G. G. Cardellino, S. Russo, C. Andreetta, G. Damante, A. Piga, F. Puglisi
Journal: Journal of Clinical Oncology (2005)

9674 Background: The molecular components of Plasminogen Activator system, Urokinase-type Plasminogen Activator (uPA) and its inhibitor PAI-1, are involved in tumor progression and have prognostic value in early breast cancer (BC) patients. The -675 4G/5G polymorphism of the PAI-1 promoter gene is associated with different activity levels of PAI-1 in serum. Cycloxigenase-2 (COX-2) expression is associated with poor prognosis in early BC. In addition, it has been shown that COX-2 modulates uPA expression. We aimed at studying the PAI-1 polymorphism together with the immunohistochemical expression of uPA, PAI-1 and COX-2 in BC patients Methods: Blood samples from a consecutive series of 199 BC patients were collected and PAI-1 -675 4G/5G polymorphism was analyzed by PCR technique. Immunohistochemical expression of uPA, PAI-1, COX-2, HER-2/neu, and MIB-1/Ki-67 was evaluated in the tissue sample of primitive BC. A score combining intensity and percentage of cellular immunoreactivity, was used to assess the staining of uPA, PAI-1, and COX-2. uPA and PAI-1 positivity was evaluated in tumor cells and stromal fibroblasts. Results: The 4G allele was associated with regional lymph node involvement (P=.04). No statistically significant association was found between genotype and immunohistochemical expression of uPA, PAI-1 and COX-2. uPA immunostaining directly correlated with estrogen receptor expression (P=.03). Negative uPA score was associated with negative hormonal receptor expression, high tumor grade, and high MIB-1/Ki-67 expression (p<.05). PAI-1 score directly correlated with COX-2 expression (P=.02), and strong PAI-1 immunostaining was associated with moderate/strong expression of COX-2 (P=.006). Tumors with PAI-1 positive fibroblasts showed higher MIB-1/Ki-67 expression (P=.02). Moderate/strong COX-2 expression was associated with HER-2/neu overexpression (P=.02). Conclusions: These findings suggest that BC patients carrying the 4G allele of the PAI-1 promoter may have an increased probability of axillary lymph node involvement. In addition, our data support a possible interaction between Plasminogen Activator and COX-2 systems. No significant financial relationships to disclose.
A phase I/II study of the hypomethylating agent azacitadine with the nanoparticle albumin bound paclitaxel in the treatment of patients with advanced or metastatic solid tumors.
Authors: T. L. Dumlao, T. W. Butler, D. L. Dyess, H. T. Khong
Journal: Journal of Clinical Oncology (2011)

3095^ Background: The efficacy of nanoparticle albumin bound paclitaxel (N) seems to correlate with the expression of tumor-associated SPARC. A common mechanism for SPARC downregulation is hypermethylation. This study investigates the use of the hypomethylating agent azacitadine (A), followed by N in the treatment of refractory advanced solid tumors. Methods: Patients with evaluable advanced solid tumors, adequate organ function, PS 0-2, and unlimited prior cytotoxic regimens were eligible. Cohorts of 3-6 patients were enrolled and treated. Escalating doses of A (75-100 mg/m2) was administered to patients SC on days 1-5, followed by a fixed dose of N (100 mg/m2) on days 8, 15, and 22 of a 28-day cycle, for a total of 6 cycles. Serum and/or tissue samples, where appropriate, were collected for correlative studies. Results: Patients were initially permitted to have an unlimited number of prior chemotherapies, but after 2 of the first 5 patients experiencing DLT (grade 4 neutropenia > 8 days), and dose reduction of N occurring in 3 patients all with 4 or more prior cytotoxic regimens, the protocol was amended to permit no more than 2 prior cytotoxic regimens. Cohort 2 was treated at the same dose level (A 75mg/m2) with no DLT. Cohort 3 was treated at the next dose level (A 100 mg/m2). Two of 4 had DLT of prolonged grade 4 neutropenia. Therefore, the MTD of A in this regimen is 75 mg/m2. Three additional patients were treated at the MTD dose with no grade 4 toxicity in cycle 1. To date, 16 patients have enrolled in the phase I part. Two patients were removed before completing cycle 1 because of disease progression. One patient was removed after cycle 4 for noncompliance. Clinical activity included 1 CR in refractory DLBC lymphoma, 2 CR in ovarian cancer, 4PR in ovarian and endometrial cancer, 4 SD in lung, sarcoma and pancreatic cancer, 1 unconfirmed PR in breast cancer, and 1 PD in CLL/SLL. Two breast cancer patients in the phase II part had unconfirmed PR and are still receiving treatments. Conclusions: A 75 mg/m2 followed by weekly N 100 mg/m2 was well tolerated and seemed to result in dramatic responses in heavily pre-treated patients with cancer of diverse histology.
The role of the <i>CYP1A1</i> gene defects in cancer risk in south-eastern Brazil
Authors: S. N. Angelo, G. G. Yamaguti, G. J. Lourenço, H. N. Honma, E. F. Silva, A. F. Sagarra, C. S. Coy, M. E. Correa, J. Jorge-Junior, C. S. Lima
Journal: Journal of Clinical Oncology (2008)

22115 Background: Several tumors have been linked to chronic exposure to polycyclic aromatic hydrocarbons (PAHs) found in food and tobacco smoke. PAHs are bioactivated by the CYP1A1 enzymes. An A→G substitution at nucleotide 4889 and a T→C substitution at nucleotide 6235 of the CYP1A1 gene lead to the production of more active enzymes. Cancer and environmental-related diseases due to tobacco exposure have been described as serious health problems in the south-eastern Brazil. Therefore, the aim of this study was to evaluate the influence of the CYP1A1 A4889G and T6235C genotypes for cancer risk in individuals of this region. Methods: DNA from 525 cancer patients, including 133 acute myeloid leukemia (AML), 250 colorectal cancer (CC) and 142 head and neck cancer (HNC), and 529 age and race-matched controls were analyzed by polymerase chain reaction and enzymatic digestion. Results: Similar frequencies of the CYP1A1 4889AG+GG genotype were seen in AML (43.6% versus 30.8%), in CC (22.0% versus 27.2%) and in HNC (33.8% versus 28.2%) patients and controls. Individuals with the distinct genotypes were under similar risks for diseases. Similar frequencies of CYP1A1 6235TC+CC genotype were seen in CC (29.0% versus 36.1%) and HNC (36.6% versus 33.8%) patients and controls. Individuals with the distinct genotypes were under similar risk for CC and HNC. However, the frequency of the CYP1A1 6235TC+CC genotype was significantly higher in AML patients than in controls (51.1% vs 28.6%; P < 0.001). Carriers of the CYP1A1 T6235C variant allele (C) were under a 2.8-fold increased risk of AML (95% CI: 1.67–4.84). Moreover, the frequency of the CYP1A1 6235TC+CC genotype was lower in patients with tumor of larinx than in those with other HN tumors (8 of 37 versus 44 of 105; P = 0.03) and higher in patients with low ingestion of vegetables than in others (46 of 133 versus 4 of 29; P = 0.024). Conclusion: These results suggest that the inherited CYP1A1 T6235C variant genotypes, involved in the pathways of carcinogens metabolism, alter the risk for AML and CC in accord to the pattern of vegetables ingestion, and the location of HNC in individuals of south-eastern Brazil. Financial support: FAPESP and CNPq No significant financial relationships to disclose.
Radiotherapy for intrahepatic cholangiocarcinoma: An analysis of the National Cancer Database.
Authors: Abdulrahman Y Hammad, George Younan, Rahul Rajeev, Nicholas Gerard Berger, Kiran Turaga, Fabian McCartney Johnston, Kathleen K. Christians, T. Clark Gamblin
Journal: Journal of Clinical Oncology (2016)

379 Background: The role of radiotherapy (RT) for surgically resected intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Radiotherapy is often considered when a positive resection margin exists. The present study sought to examine the impact of radiotherapy following liver resection. Methods: Patients with early stage ICC, who underwent surgical resection, were identified from the National Cancer Database (1998-2011). Patients were stratified by resection margin status and receipt of RT. Survival was analyzed by Kaplan-Meier method and a multivariate regression model was used to identify predictors of survival. Results: A total of 2,182 patients were identified. R0 status was obtained in 1,624 patients (74.4%). RT was delivered to 405 patients (R0=209, R1/R2=196). In the R1/R2 group, 196 patients received RT vs. 362 R1/R2 patients that did not receive RT. Survival for R0 vs. R1/R2 was 32m vs. 16.5m (p&lt;0.001). RT appeared to trend toward improving survival for R1/R2 patients, though this was not significant (20.4m vs. 14.5m, p=0.191). In a multivariate model accounting for age, sex, comorbidities, disease stage and resection margins, RT was not a predictor of survival. Negative predictors of survival included age&gt;65years (Hazards Ratio [HR]: 1.20 (95%CI: 1.04-1.39), p=0.013), and positive resection margins (HR: 1.95 (95%CI: 1.65-2.30), p&lt;0.001). Female sex was the only positive predictor of survival identified (HR: 0.76 (95%CI: 0.65 -0.88), p&lt;0.001). Conclusions: Surgical resection with negative margins provides the best outcome for patients with ICC. Radiotherapy does not appear to significantly impact survival in patients with positive resection margins.
A randomized phase III study of iniparib (BSI-201) in combination with gemcitabine/carboplatin (G/C) in metastatic triple-negative breast cancer (TNBC).
Authors: J. O'Shaughnessy, L. S. Schwartzberg, M. A. Danso, H. S. Rugo, K. Miller, D. A. Yardley, R. W. Carlson, R. S. Finn, E. Charpentier, M. Freese, S. Gupta, A. Blackwood-Chirchir, E. P. Winer
Journal: Journal of Clinical Oncology (2011)

1007 Background: A randomized phase II study in mTNBC suggested that iniparib (I), an anticancer agent with PARP inhibitory activity, added to GC improved overall survival (OS), without potentiating GC toxicity (O'Shaughnessy et al. NEJM 2011). This confirmatory study evaluated the safety and efficacy of GC with or without I in a similar mTNBC pt population. Methods: This randomized, open-label phase III study enrolled pts ≥18 years with mTNBC, measurable disease, and ≤2 prior cytotoxic regimens for metastatic TNBC. Pts were stratified based on having 0 vs. 1–2 prior metastatic therapies. Pts were randomized (1:1) to GC alone or GCI. G (1000 mg/m2; IV) and C (AUC 2; IV) were given on days 1 and 8, and I (5.6 mg/kg; IV) on days 1, 4, 8, and 11 every 21 days. Upon central confirmation of disease progression on GC, crossover to GCI was permitted. Primary endpoints were OS and progression-free survival (PFS); secondary endpoints were objective response rate and safety. Results: Between July 2009 and March 2010, 519 pts were randomized. Pt characteristics were balanced between the two arms. The study did not meet the criteria for significance for co-primary endpoints of OS and PFS. Efficacy results in pts stratified by line of therapy (57% in 1st line; 43% in 2nd or 3rd line) will be presented. 152 of 258 GC pts (59%) crossed over to receive GCI following disease progression. Most frequently occurring grade 3/4 adverse events included neutropenia (53% [GC] vs. 61% [GCI]), anemia (22% vs. 18%), thrombocytopenia (24% vs. 28%), and leukopenia (15% vs. 16%). Overall, addition of I did not significantly add to the toxicity profile of GC alone. Conclusions: Although this study demonstrated a consistent safety profile to that of the phase II study, addition of I to GC did not meet the pre-specified criteria for significance for co-primary endpoints of OS and PFS in pts with mTNBC. Analyses aimed at further elucidating these findings are ongoing (clinicaltrials.gov: NCT00938652). GC (n = 258 ) GCI (n = 261) Hazard ratio (95% CI) P value* Median OS, months 11.1 11.8 0.876 (0.687−1.116) 0.284 Median PFS, months 4.1 5.1 0.794 (0.646−0.976) 0.027 * Based on 2-sided log-rank test.
A proposal for the management guideline of superficial esophageal squamous cell carcinoma: After endoscopic resection.
Authors: Yong Chan Lee, Jun Chul Park, Sung Kwan Shin, Sang Kil Lee, Hyun Jik Lee
Journal: Journal of Clinical Oncology (2016)

145 Background: We tried to analyze and deduce a treatment guideline after endoscopic resection of superficial esophageal squamous cell carcinoma in a retrospective analysis. Methods: Medical records of 37 patients who had been treated by endoscopic resection during a 6-year period in single institution were retrospectively analyzed. Results: Mean tumor size was 11.5±5.5 mm (range 3-31). Thirty-one lesions (83.8%) were treated by endoscopic submucosal dissection and 6 lesions by endoscopic mucosal resection (16.2%). En bloc resection rate and complete resection rate was 91.9% and 81.8%, respectively. The tumor invasion depth was diagnosed as epithelium: 5(13.5%), lamina propria mucosa: 12 (32.4%), muscularis mucosa: 10 (27.0%), submucosa: 10 (27.0%) respectively. The lymphovascular invasion was 3 lesions (8.1%). The rates of adverse events were 13.5% including 3 cases (8.1%) of perforation. Ten patients of the invasion depth as muscularis mucosa and submucosa received additional treatments including 6 patients of esophagectomy, 3 patients with radiotherapy and 1 patient with chemoradiotherapy. One patient of lamina propria received radiotherapy due to resection margin positive. The median follow-up duration was 22 month (range, 4-79) and there was no recurrence or metastasis during follow-up. Conclusions: We propose that adequate tailored management strategy after endoscopic resection of superficial esophageal squamous cell carcinoma may provide the favorable clinical results in outcome in treating early stage esophageal carcinoma.
Strength training to enhance early recovery after hematopoietic stem cell transplantation.
Authors: Eileen Danaher Hacker, Eileen Collins, Chang Park, Tara Peters, Damiano Rondelli
Journal: Journal of Clinical Oncology (2016)

190 Background: Intensive cancer treatment followed by hematopoietic stem cell transplantation (HCT) results in moderate to severe fatigue and physical inactivity leading to diminished functional ability. Methods: This study compared strength training to enhance early recovery (STEER) (n = 33) to attentional control with health education (n = 34) in adult HCT patients on primary outcomes (physical activity and fatigue) and secondary outcome (functional ability) in a single-blind randomized clinical trial. Subjects were randomly stratified by type of transplant (allogeneic or autologous) and age (≤ 60 years of age or &gt; 60 years of age). STEER consisted of a comprehensive program of progressive resistance introduced during hospitalization and continued for six weeks following hospital discharge. Attention control with health education subjects received structured weekly health education post hospitalization. Variables were assessed prior to HCT hospital admission and six weeks following hospital discharge. Using the two-sided alpha level of 0.05, a final sample size of 66 (n = 33 per arm) was planned with 80% statistical power. Data were analyzed using split-plot ANOVAs. Results: Interactions effects were noted for fatigue, p = .04, η p 2 = .06. The STEER group reported more fatigue at baseline and less fatigue following strength training compared to the health education group. Time, p &lt; .001, η p 2 = .16, and group effects, p = .05, η p 2 = .05, were observed for physical activity. Physical activity decreased from baseline to six weeks post hospitalization. The STEER group was more physically active. Group effects were observed for two functional tests (15-foot timed walk, p = .04, η p 2 = .06; and, timed up and go test, p = .03, η p 2 = .07). The STEER group completed both tests faster. The timed stair climb, p = .03. η p 2 = .07, and timed up and go tests, p = .05, η p 2 = .06, interaction effects. The STEER group completed both tests faster following completion of strength training. Conclusions: Strength training enhances early recovery following HCT with moderate effect sizes. Strength training significantly reduced fatigue while improving physical activity and functional ability six weeks following hospital discharge.
Mesenchymal Stems Cells and Regulatory T Cells Inhibit Alloantigen Mediated Graft-Versus-Host Reaction but Also Impair Graft-Versus-Tumor Reactions Targeting Tumor Associated Antigens
Authors: Matthias Stelljes, Sarah Harmata, Verena Schlösser, Corinna Opitz, Jörn Albring, Felix Rosenow, Bülent Sargin, Wolfgang E. Berdel, Joachim Kienast
Journal: Blood (2008)
Enrichment of disseminated tumor cells (DTC) in bone marrow (BM) from patients with breast cancer (BC) using a magnetic cell sorting device (MCSD)-Method and prognostic significance
Authors: D. V. Oruzio, D. Hempel, M. Finkl, S. Ehnle, D. Steinfeld, A. Wischnik, J. Witte, G. Schlimok
Journal: Journal of Clinical Oncology (2005)

9640 Background: There is increasing evidence that immunocytochemical detection (ID) of DTC in BM from patients with BC probably has prognostic significance. But the low detection rate hampers further geno- and phenotyping and the efficiency of DTC as a broadly applied prognostic tool. We studied the possibility to enrich DTC using immunomagentic beads coupled mab against human epithelial antigen (HEA) with MCSD and the prognostic significance. Methods: BM from 107 patients with stage I to IV BC were taken. After separation of mononuclear cells (MNC) (Ficoll-Hypaque density gradient), a cytospin with 1x106 MNC was made and studied for the presence of DTC using a mouse mab F(ab)2-fragment (mab A45B/B3) directed against human cytokeratines and coupled to alkaline phosphatase. The remaining portion of the MNC was incubated with mab against HEA conjugated with magnetic microbeads. Thereafter DTC were enriched with MCSD (Miltenyi-Biotec). After washing, cytospins with 1x106 MNC were made and examined for the presence of DTIC using mab A45 B/B3. Results: The detection rate and the number of DTC in enriched and not enriched samples correlates with tumor stage (Spermann-Rho 1,0;p=0,01). Using MCSD the detection rate and the number of DTC could be improved for every tumor stage. It was statistically significant for stage I and II diesease (McNemar-Test:p<0,0001). There is a trend for better PFS and OS in the group without DTC in BM (enriched and not enriched), but it was not found to be a statistically significant indipendent risk factor (Logrank-Test). Conclusions: Enrichment of DTC from BM in patients with BC using MCSD is a more sensitive method for detection and quantification of DTC than ID alone, especially in early stages of the disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Micromet Micromet