tbuckley/cabot-search huggingface dataset:
Parameningeal rhabdomyosarcoma: Results of a pooled analysis from U.S. and European Cooperative Groups.
Authors: J. H. Merks, G. L. De Salvo, C. Bergeron, G. Bisogno, A. Rey, O. Oberlin, A. Kelsey, I. Zanetti, J. M. Michalski, D. S. Hawkins, J. R. Anderson
Journal: Journal of Clinical Oncology (2011)

9529 Background: Parameningeal (PMN) site is a well known adverse prognostic factor in children with localized rhabdomyosarcoma (RMS). To identify risk factors associated with outcome we pooled data from 1105 consecutive patients treated in ten studies conducted by European and North-American cooperative groups between 1984 and 2004. Methods: Clinical factors including age, histology, size, invasiveness, nodal involvement, IRS clinical group, site of primary, risk factors for meningeal involvement (MI), study group (Children’s Oncology Group, International Society of Pediatric Oncology, Italian Cooperative Group), type and duration of chemotherapy (CT), and application of radiotherapy (RT) were studied for their impact on event free- and overall survival (EFS and OS). Results: The five and ten year EFS and OS are 64.9 and 62.6 (EFS) and 69.5 and 66.1 (OS). By multivariate analysis OS is significantly adversely associated with 6 factors: 1. omission of RT for patients with tumors at favorable sites (i.e. middle ear, mastoid, nasal cavity, nasopharynx, parapharyngeal space, and non PMN head and neck- or orbital primaries with PMN extension), 2. signs of MI (cranial nerve palsy and/or cranial base bony erosion, intracranial extension (ICE)), 3. age ≤1 year, 4. unfavorable site (infratemporal and pterygopalatine fossa, paranasal sinus) for patients that received RT, 5. alveolar histology, and 6. tumor size >5cm. Multivariate analysis for OS focused on patients who received RT reveals the following unfavorable prognostic factors: 1. age ≤1year, 2. signs of MI, 3. unfavorable site, and 4. tumor size >5cm. According to prognostic factors, patients could be classified in different risk groups with 10-yr OS ranging between 49.9 to 84.1%. Among risk factors for MI, only ICE is associated with an increased risk for central nervous system failure. Patients <3 years without RT show worse survival (10-yr OS +/- RT: 41.7 vs 63.9). Conclusions: This analysis underlines the absolute necessity for RT in PMN RMS especially in the very young and further refines prognostic factors in PMN RMS.
Effect of RAD21 overexpression on prognosis in <i>KRAS</i>-mutant colorectal carcinomas.
Authors: Thomaz De Campos Silva, Siddhartha Deb, Huiling Xu, Yuqian Yan, Stephen B. Fox, Neil Mortensen, Michael McKay
Journal: Journal of Clinical Oncology (2014)

453 Background: RAD21 is a component of the cohesion complex and is integral for chromosome segregation and error-free DNA repair. Early studies suggest RAD21 appears to be functionally important in tumour progression and we assessed its clinicopathological and prognostic significance in a cohort of colorectal adenocarcinoma (CRC), and its biological characteristics and cell cell chemosensitivity in vitro. Methods: A multi-institutional study examined RAD21 expression in 652 invasive CRC's. Correlation with clinicopathological factors including gender, differentiation, subtype, nodal status, metastasis and disease specific survival was performed. Correlation with BRAF and KRAS mutation status, p53 accumulation, microsatellite instability, and CpG island methylator phenotype was also undertaken. Cell clones with stable RAD21 knockdown were generated and tested for cellular sensitivity to conventional chemotherapeutic drugs. Results: High RAD21 expression correlated with male gender (56.7% vs. 43.3%), more well differentiated tumours (14.4% vs. 4.0%, p = 0.0001), higher T stage (36.1% vs. 27.0%, p = 0.01), and presence of metastasis (18.8% vs. 12.6%, p =0.03). Both on univariate and multivariate analysis, increased RAD21 expression correlated with worse DSS (hazards ration [HR] 1.4, 95% confidence interval [CI] 1.1 to 1.9, p = 0.01). Subgroup analysis showed RAD21 expression was prognostic in female patients (HR:1.6, 95%CI:1.1-2.3, p = 0.01) and tumours with nodal disease (HR:1.6, 95%CI:1.2-2.2, p = 0.003). RAD21 expression associates worse DSS in patients whose tumors carrying KRAS mutations (HR:2.6, 95%CI:1.4-4.3, p = 0.001), or p53 accumulation (HR:2.2, 95%CI:1.2-4.1, p = 0.02) and in patients receiving adjuvant chemoradiotherapy (HR:1.9, 95%CI:1.2-3.0, p = 0.005). Cells with reduced RAD21 expression exhibited enhanced sensitivity to 5-FU, alone or with Oxaliplatin. Conclusions: RAD21 expression in CRC is associated to advanced disease stage and confers poorer overall prognosis and resistance to chemoradiotherapy. RAD21 expression is of prognostic significance in tumours with somatic KRAS mutations or p53 accumulation. In these subgroups, RAD21 may be a novel important therapeutic target.
Implantable marker to facilitate use of hypofractionated radiation in early breast cancer.
Authors: Michael Cross, Joe Ross, Scott Jones, Arnold Smith, Thadeus Beck
Journal: Journal of Clinical Oncology (2015)

38 Background: Shorter courses of radiation therapy have advantages for patients and could result in significant cost savings for the healthcare system. The British and Canadian experience with hypo-fractionated regimens have shown that survival rates in appropriately selected patients is equivalent to other methods. However, adoption of these techniques has been hindered by fear of potential complications such as poor cosmetic outcomes. By improving targeting of the surgical tumor bed, an increased use of "field in field" planning helps to decrease "hot spots" commonly related to toxicities. This could potentially assist with increased use of hypo-fractionated regimens in a reliable, safe and cost-effective manner. To determine the ability of a new surgical implant marker to facilitate use of hypofractionated radiation delivery, we prospectively studied the radiation regimens delivered to 100 patients implanted with the device in our community-based practice. Methods: Over a 36 month period, 110 volumetric tissue markers were surgically implanted at the tumor bed excision site in 109 patients during partial mastectomy (PM). Routine CT imaging of the breast was performed for treatment planning and the marker was rated for visibility and its utility in delineating the target region. Radiation treatment regimens were recorded and reported. A cost analysis was also performed. Results: In all patients, the marker was easily visible and in 95.7% of cases, it was found to be useful during radiation treatment planning for RT target delineation. 36.8% of patients received conventional full-course whole breast irradiation plus boost, 56.6% received hypo-fractionation plus boost, and 4.3% received accelerated partial breast irradiation. With routine use of the implant, there was a marked increase in the use of hypo-fractionated regimens, resulting in a 25% cost savings per patient. Conclusions: This 3-dimensional implant was easily visible and particularly useful in targeting the tumor bed when implanted during PM. With routine use of the device we observed an unanticipated increased use of accelerated radiation protocols, a net cost savings in patients' treatment and a significant improvement in cosmetic outcomes.
Investigations of breast cancer screening using a novel in vitro diagnostics technology.
Authors: Hongmei Tao, Xuedong Du, Xing Tang, Yue Lin, Da Lou, Chris Chang Yu
Journal: Journal of Clinical Oncology (2015)

13 Background: A newly developed in-vitro diagnostic technology named Cancer Differentiation Analysis Technology (CDA) was investigated for breast cancer screening. The CDA technology is a blood-sample based, multi-level, multi-parameter diagnostic method which detects signals from both proteins and cells, in which multiple aspects and parameters of information were collected to improve diagnostic accuracy. Methods: Blood samples from breast cancer group (n = 222), and control subjects (n = 204) were collected in EDTA tubes. CDA values were measured using a CDA medical device. The results were shown in Table 1 and Figure 1 below. Results: The average CDA values of breast cancer and control groups were 50.43 and 34.03 (rel. units) respectively. The results indicated that breast cancer could be significantly distinguished from the control (p &lt; 0.001). Area under ROC curve was 0.914. When Youden Index reached the maximum, sensitivity and specificity was 82.0% and 89.2% respectively. Conclusions: Initial results showed that CDA technology could be a potential candidate for breast cancer screening. [Table: see text]
Intravesical gemcitabine versus mitomycin for recurrent superficial bladder tumors (Stages pTa and pT1): A randomized prospective study
Authors: L. Montella, R. Addeo, S. Bellini, V. Faiola, L. Tarantino, C. Pizza, A. Schiano, R. Guarrasi, A. Miragliuolo, S. Del Prete
Journal: Journal of Clinical Oncology (2008)

5075 Background: Approximately 30–40% of patients with a superficial bladder cancer treated with Bacille Calmette-Guerin (BCG) or epirubicin do not respond and other 35% of initial responders have a relapse within 5 years. We have compared the therapeutic efficacy and toxicity of intravesical Gemcitabine (GEM) with Mitomycin C (MMC) in patients with recurrent superficial bladder cancer. Methods: Patients with previously treated recurrent Ta-T1, G1-G2 bladder transitional cell carcinoma were enrolled in the present study and randomized to a 6-week course of GEM instillations (2000 mg in 50 ml saline) or 4-week course of MMC (40 mg). In both arms, for the initial responders who remained free of recurrences, maintenance therapy consisted of a 10 monthly treatment during the first year. All patients were followed every 6 months by cystourethroscopy. Results: 120 patients were included in the present study. 109 patients (55 in MMC arm and 54 in GEM arm) were evaluable. The median duration of follow-up was (identical for both groups) 34 months. In the GEM group 42 (78%) patients remained free of recurrence compared to 37 (67%) patients in the MMC group (p=0.05). 10 patients in the MMC arm and 6 in the GEM group had progressive disease by stage: either local urothelial spread, or muscle infiltration, in 5 and 3 patients, respectively. Local toxicity was acceptable in both treatment groups. The risk of. chemical cystitis in MMC arm was higher than in GEM group (p=0.012). Conclusions: Intravesical therapy with GEM is active and better tolerated than MMC in refractory transitional cell patients. Final results will be presented at 2008 ASCO Meeting. No significant financial relationships to disclose.
A nomogram based on clinical factors to predict locally advanced stage of rectal cancer.
Authors: Guoxiang Cai, Baorong Song, Liyong Huang, Ye Xu, Zuqing Guan, Weiqi Sheng, Sanjun Cai
Journal: Journal of Clinical Oncology (2013)

376 Background: Preoperative staging of rectal cancer is important for designing treatment strategy. The standard treatment for locally advanced rectal cancer is neoadjuvant radiochemotherapy followed by surgery. Magnetic resonance imaging (MRI) and transrectal ultrasonography are major staging approaches with a prediction accuracy of about 70-80% but not widely available in hospitals in China. We sought to define possible clinicopathological predictors and establish a simple nomogram as a reference tool for patients and clinicians to predict stage of rectal cancer and make decisions about neoadjuvant therapy. Methods: Preoperative staging of rectal cancer is important for designing treatment strategy. The standard treatment for locally advanced rectal cancer is neoadjuvant radiochemotherapy followed by surgery. Magnetic resonance imaging (MRI) and transrectal ultrasonography are major staging approaches with a prediction accuracy of about 70-80% but not widely available in hospitals in China. We sought to define possible clinicopathological predictors and establish a simple nomogram as a reference tool for patients and clinicians to predict stage of rectal cancer and make decisions about neoadjuvant therapy. Results: In the training set, 77.1% of patients had locally advanced stage by pathology. The multivariate analysis indicated that tumor size (Odds ratio (OR)=1.55, p&lt; 0.001), differentiation (OR =0.38, p&lt; 0.001), location (OR =1.06, p=0.038), serum CEA (OR =0.24, p&lt; 0.001) and CA19-9 level (OR =0.13, p&lt; 0.001) were associated with tumor stage. A nomogram consisting of these 5 factors was developed and predicted locally advanced stage with a concordance index of 0.756. The concordance index of this nomogram was 0.800 in the validation set. Conclusions: Large tumor size, far from anal verge, poor differentiation, elevated serum CEA and CA19-9 level were high-risk factors of locally advanced stage of rectal cancer. The nomogram based on these clinical factors can predicte locally advanced rectal cancer with a considerable accuracy and thus helpful for making neoadjuvant therapy recommendations.
Concomitant chemoradiotherapy (CT/RT) vs neoadjuvant chemotherapy with docetaxel/cispaltin/5-fluorouracil (TPF) followed by CT/RT in locally advanced head and neck cancer. Final results of a phase II randomized study
Authors: A. Paccagnella, A. Buffoli, H. Koussis, A. Gava, T. Franceschi, G. Gardani, F. Valduga, F. Gaion, D. Dondi, M. G. Ghi
Journal: Journal of Clinical Oncology (2008)

6000 Background: Concomitant CT/RT is the standard treatment for locally advanced head and neck squamous cell carcinoma. This trial explores the efficacy of induction chemotherapy with TPF before concomitant CT/RT and concomitant CT/RT alone in locally advanced unresectable disease. Patients and Methods: From January 2003 to January 2006, 101 patients (pts) with stage III- IV M0, PS 0–1, were randomized to 2 cycles of cisplatin (P) 20mg/sqm days 1–4, 5FU (F) 800 mg/sqm 96-hour CI wks 1 and 6 during RT (66–70 Gy) (Arm A) or 3 cycles TPF (docetaxel 75 mg/sqm and P 80 mg/sqm on day 1, F 800 mg/sqm 96 hours CI) every 3 weeks followed by the same CT/RT (Arm B). Neck dissection was planned for pts with stage N2-N3 and pathological complete response (CR) at the primary tumor. A minimum accrual of 96 pts was required to detect a difference in radiological CR (primary endpoint) of at least 15% in favor of arm B. Results: Pts/tumor characteristics were well balanced in the two arms. During TPF, G3–4 neutropenia was the main hematological toxicity (52%) while nonhematological toxicities were mild. CR rate after TPF was 6.5%. During concomitant CT/RT, hematological and nonhematological toxicities were not increased in the experimental arm B and the feasibility of CT/RT was not compromised. Grade 3–4 toxicities in arms A and B, respectively, were mucositis 38% and 25%, dysphagia 21% and 16%, skin reaction 13% and 15%, weight loss 2% and 4%. Radiological evaluation (CT or MRI scan) of responses 6–8 weeks from the end of CT/RT showed a CR of 21.2% (CI: 64–89) in arm A and 50.0% (CI: 34–65) in arm B. Radiological CRs at 8 months for unresected pts were 40.0% in Arm A and 57.1% in Arm B. Median OS and 1-yr OS were respectively 33.3 months and 77.6% in Arm A, while median OS was not reached in arm B and 1-yr OS was 86.0%. Conclusions: Neoadjuvant TPF is feasible and does not compromise subsequent concomitant CT/RT. Compared with CT/RT, induction TPF plus CT/RT significantly improves clinical CR evaluated at 8 weeks and 8 months after the end of the treatment. A trend for improved OS was also observed. The phase III part of the study with survival as the primary end-point is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis sanofi-aventis
Retrospective study comparing cisplatin to carboplatin-based chemotherapy in Chinese patients with advanced non-small cell lung cancer.
Authors: D. Zheng, J. Luo, Y. Xu
Journal: Journal of Clinical Oncology (2010)

e18135 Background: It remains controversial whether cisplatin has the superior efficacy compared to that of carboplatin for advanced non-small cell lung cancer (NSCLC). Retrospective analysis was conducted to compare cisplatin-based chemotherapy with carboplatin-based chemotherapy. Methods: In a retrospective trial we evaluated the clinical efficacy and toxicity profile of cisplatin- and carboplatin-based chemotherapy given to advanced NSCLC patients with Eastern Cooperative Oncology Group performance status score(PS) of 0-1, whose survival times were over 90 days. The primary end points were overall survival (OS) and safety. Potential predictive factors of efficacy were also analysed. Results: From January 2002 to December 2008, 1014 patients met the inclusion criteria and were evaluable. 788 patients received at least 2 cycles of cisplatin-based doublet regimen and 226 carboplatin. All clinical characters at baseline were well balanced. The cisplatin-based regimen yield significant better OS with a median survival time of 10 months compared to that of the carboplatin-based regimen at 8.9 months, attributable to the survival benefit of patients with stage III B, or age less than 70. No significant differences were observed when grade 3 or 4 adverse events were compared. Conclusions: We found that the cisplatin-based chemotherapy produced substantial survival advantage compared to the carboplatin-based chemotherapy in NSCLC patients with stage IIIB or age less than 70. Prospective randomized trials recruiting NSCLC patients to study subgroup characteristics that would most likely receive the optimal therapy from each double regimen are needed. No significant financial relationships to disclose.
Prospective evaluation of prognostic factors for recurrence after complete surgical resection of gastrointestinal stromal tumors (GIST)
Authors: V. S. Suhag, D. J. Perry, D. Kumar, L. Amiri-Kordestani, J. S. Jelinek, D. A. Priebat
Journal: Journal of Clinical Oncology (2008)

10558 Background: The clinical course of GISTs can be highly variable, depending on their size, mitotic index and location. Imatinib has been effectively used to treat recurrent and metastatic GIST, but its role in the adjuvant setting is still evolving. Analyzing factors which predict recurrence will help identify subgroups of patients who will benefit the most from adjuvant imatinib therapy. Methods: We analyzed the following factors in a prospective series of patients with GIST: age, sex, location, size and mitotic index of the primary, recurrence rates and overall survival. Results: From April 1999 to May 2007, 37 patients with primary localized GIST who underwent complete surgical resection, were c KIT positive and received no adjuvant imatinib were evaluated and followed. Median age at diagnosis was 62 years (range 18-82 years); 59 % were females; median size was 5.5 cm (1.1- 19 cm) and the median duration of follow up was 37 months (7- 97 months). Stomach was the most common site of presentation (76 %) followed by small intestine (16 %) and colon (5 %). Seventeen (46 %) patients had tumors ≤ 5 cm, 10 (27 %) had tumors 5–10 cm and 10 (27 %) patients had tumors ≥ 10 cm. Twenty seven patients (73 %) had ≤ 5 mitosis/ 50 high power field (HPF), 3 patients (8 %) had 5–10 mitosis per 50 HPF and seven patients (19 %) had ≥ 10 mitosis per 50 HPF. Thirty of 37 (81 %) were free of recurrence and overall survival was 97 % (one patient in remission died of myocardial infarction). In patients who had a recurrence the median size of the tumor was 14 cm (range 5.5- 19 cm) and median duration from diagnosis to recurrence was 27 months (12- 65 months). Outcome data on recurrence rates is presented in the table with statistical comparison between the various groups studied. Conclusions: Patients presenting with GIST ≥ 10 cm, mitotic index ≥ 10 per 50 HPF or small intestine as their primary site remain at high risk for recurrence with long term follow up and would appear to be a subset which is more likely to benefit from adjuvant imatinib. Factors affecting recurrence rates in GIST Factor Recurrence N (%) No recurrence N (%) p value (Fisher’s exact test) Tumor size < 10 cm 1 (4%) 26 (96%) 0.0006 Tumor size ≥10 cm 6 (60%) 4 (40%) Primary site Stomach 3 (10%) 25 (90%) 0.0096 Primary site Small Intestine 4 (66%) 2 (33%) Mitosis < 10/50 HPF 0 (0%) 30 (100%) 0.00009 Mitosis ≥ 10/50 HPF 7 (100%) 0 (0%) N= Number of patients Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Novartis Novartis
Investigating autophagy and glutamine metabolism as therapeutic targets for pancreatic cancer.
Authors: Mario Jardon, Steve Kalloger, Christina Iggulden, Nancy Erro Go, Paalini Sathiyaseelan, Donald Yapp, Daniel John Renouf, David Schaeffer, Sharon Gorski
Journal: Journal of Clinical Oncology (2015)

381 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest types of cancer, for which new therapeutic approaches are urgently needed. We are developing novel combination therapy approaches based on the inhibition of glutamine metabolism and autophagy, to improve current treatments for PDAC. Since both processes are key mediators of multiple cancer hallmarks, and have inter-related but non-redundant roles, this combination may result in a more efficient disruption of cancer cell resistance to treatments. Methods: We interrogated the Pancreas Centre BC tissue micro-array, containing the epithelial component of 252 PDAC samples, for expression of three key glutamine-metabolizing proteins and two autophagy-related proteins: glutamine synthetase (GLUL), asparagine synthetase (ASNS), glutaminase C (GLS-GAC), microtubule-associated protein 1 light chain 3 beta (MAP1-LC3B or LC3B) and autophagy-related protein 4B (ATG4B). While previous efforts by other groups have focused on GLS-GAC, the role of GLUL in cancer has remained less well understood. We thus investigated the functional relevance of GLUL using a panel of PDAC cell lines. We are also investigating interactions between glutamine metabolism and autophagy, including the exploration of strategies to target GLUL and the evaluation of a new class of ATG4B inhibitors for the treatment of pancreatic cancers. Results: We found that GLUL, ASNS, GLS-GAC, LC3B and ATG4B were expressed in 31%, 58%, 99%, 51% and 73%, respectively, of PDAC samples. Furthermore, higher LC3B expression correlated with poor outcome. Our functional studies revealed that various PDAC cells express GLUL, which can be upregulated upon glutamine deprivation. In all cell lines tested, GLUL knockdown sensitized them to gemcitabine, as assessed by a long-term recovery assay. We also found that the candidate ATG4B inhibitors, shown to inhibit this target in cell-free assays, effectively inhibit PDAC cell proliferation at micromolar concentrations. Conclusions: Our study reveals that glutamine metabolism and autophagy are clinically relevant in PDAC and may have potential as therapeutic targets. Supported by Pancreas Centre BC, BC Cancer Foundation and VGH Foundation.