tbuckley/cabot-search huggingface dataset:
Final results of RTOG 0246: A phase II study of selective surgical resection for locoregionally advanced esophageal cancer treated with a paclitaxel-based chemoradiation regimen.
Authors: Stephen Swisher, Jennifer Moughan, Ritsuko Komaki, Jaffer A. Ajani, Tsung-Teh Wu, Wayne Lewis Hofstetter, Andre A. Konski, Christopher Willett
Journal: Journal of Clinical Oncology (2013)

7 Background: The organ preserving strategy of selective esophageal resection after definitive chemoradiation was evaluated in a multi-center, prospective Phase II trial. Methods: Treatment involved induction chemotherapy with 5-FU (650 mg/mg 2 /d), cisplatin (15 mg/mg 2 /d) and paclitaxel (200 mg/mg 2 /d) for 2 cycles followed by concurrent chemoradiation with 50.4 Gy (1.8 Gy/fx) and daily 5-FU (300 mg/mg 2 /d) with cisplatin (15 mg/mg 2 /d) over the first 5 days. Following definitive chemoradiation, pts were evaluated for residual locoregional disease with chest and abdominal CT scans, EUS and optional PET scans. If there was no suspected residual disease patients were observed and monitored serially for recurrent disease at 3 mos x 2, 6 mos x 3 and then yrly. Esophageal resection was considered only for pts with suspected residual or recurrent locoregional esophageal cancer that did not have systemic disease. Results: 43 pts from Sept 2003 to March 2006 with non-metastatic resectable esophageal cancer were entered from 19 sites to RTOG 0246. 41 pts were eligible for analysis. 29 pts (73%) were adenocarcinoma histology with pretreatment clinical stage T3 or greater in 31 pts (76%) and N1 in 29 pts (71%). Following induction chemotherapy and chemoradiation 3 pts (7.3%) died of treatment related deaths and 1 pt died of disease progression. 21 pts (51%) underwent surgical resection following chemoradiation because of suspected residual disease 17 pts (41%), pt choice (1) or recurrent locoregional disease 3 pts (7%). 1 pt died postoperatively from esophageal anastomotic leak. 11 pts (27%) are alive and free of disease 70 to 90 months after chemoradiation, of which 5 (12%) did not have esophagectomy. With a median follow-up of 6.7 yrs (for 16 alive pts), the estimated overall 2.5 and 5-year survival rates (95% CI) are 46.3% (30.7%-60.6%) and 36.6% (22.3%-51.0%). Conclusions: The long-term results from this multi-center, prospective Phase II trial demonstrates the efficacy of a selective surgical resection approach following definitive chemoradiation in a predominantly adenocarcinoma population of locoregionally advanced esophageal cancer. Clinical trial information: NCT00081289.
O(6)-methylguanine DNA-methyltransferase (MGMT) in glioblastoma: Analysis on first and following surgeries.
Authors: F. Bertolini, C. Baraldi, E. Zunarelli, A. Valentini, R. Depenni, A. Falasca, F. Bertoni, F. Cavalleri, A. Chiari, A. Fontana, P. F. Conte, G. Pinna
Journal: Journal of Clinical Oncology (2011)

2097 Background: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Outcome has recently improved with the introduction of post-operative concomitant chemoradiotherapy (CRT) followed by 6 cycles of temozolomide (TMZ). MGMT expression has already been encoded as an independent prognostic factor and predictive for TMZ sensitivity, but few data are available on the modifications of MGMT status after CRT. Methods: From January 2005 to November 2010 at Modena University Hospital and Nuovo Ospedale Civile S. Agostino-Estense, 15 consecutive patients (pts) with GBM and treated with at least 2 subsequent surgeries were included in this retrospective study. Aim of the present analysis is to evaluate if methylation status may change between first and following determinations. Results: Fifteen pts (M/F=10/5; median age: 48, range: 40-67 years) underwent a first surgery for GBM. MGMT status was: methylated in 5 (33%); unmethylated in 10 pts (77%). Two unmethylated pts presented an early relapse and underwent a second surgery after 41 and 46 days, respectively. MGMT analysis confirmed the absence of methylation. One pt with multifocal GBM was treated after the first surgery on right frontal lobe with TMZ, operated on left frontal lobe, submitted to CRT, then re-operated for a relapse in the first site of surgery (right frontal lobe). In this case MGMT status evaluated in the site of relapse (right frontal lobe) changed from unmethylated to methylated. MGMT on the lesion of left frontal lobe was unmethylated. The remaining 12 pts underwent post-operative concomitant CRT followed by monthly TMZ (median number of cycles: 8.5; range: 2-24). MGMT status on second surgery was: 5 methylated (42%) and 7 unmethylated (58%), with a 100% concordance. Two pts received a third surgery: in one case MGMT status changed from unmethylated to methylated. Overall median survival was 15.8 months. The two patients with “MGMT switch” have a median survival of 35.8 months. Conclusions: in 2 on 13 cases (15%) after CRT, MGMT status changed from unmethylated to methylated and these pts have a median overall survival similar to methylated pts. This observation may be confirmed on larger series.
Clinical outcome of KRAS-mutated advanced non-small cell lung cancer (NSCLC) patients (pts): A mono-institutional analysis.
Authors: R. Chiari, V. De Angelis, C. Bennati, C. Molica, G. Metro, S. Duranti, F. R. Tofanetti, V. Ludovini, V. Minotti, L. Crino
Journal: Journal of Clinical Oncology (2011)

7580 Background: In the present analysis we evaluated the clinical outcome of KRAS mutated advanced non-small cell lung cancer (NSCLC) patients (pts) treated at a single Institution from April 2007 to December 2010. Methods: KRAS mutational status was assessed on tumor tissue collected at the time of first diagnosis (either primary or metastatic). KRAS (exons 2 and 3) gene was amplified by nested PCR and sequenced in both sense and antisense direction using 3500 Genetic Analyzer. Retrospective chart review was approved by the local Ethics Committee. Results: 64 pts with an identified KRAS mutation were evaluable for the analysis. The majority of them (87.5%) had a good performance status (ECOG 0), while 82.5% were former or current smokers. All pts except for one who was treated with single-agent gemcitabine, received a platinum-based doublet mainly including either gemcitabine (56,5%) or pemetrexed (25%). Overall, 82% of pts received at least two lines of chemotherapy. Three types of KRAS mutations were identified, the most common being codon 12 (78.1%) mutation, followed by codon 13 (12.5%) and codon 61 (9.4%) mutations, respectively. Of the 52 (81,2%) who were evaluable for response 2 complete responses (3,8%), 21 partial responses (40,4%), 13 disease stabilizations (25%) and 16 progressive diseases (30,8%) were observed. Median overall survival (OS) from the beginning of treatment was 39 months, with no statistically significant differences according to the type of K-RAS mutation (p< 0,2). Median OS and first-line PFS were significantly higher in responders versus non-responders (55.4 months versus 24.8 months for OS and 11.2 months versus 4.8 months for first-line PFS, p<0.009). Conclusions: KRAS mutated NSCLC pts do not represent a population with homogeneous clinical characteristics. Response to treatment seems to predict benefit from first-line chemotherapy in terms of OS and first-line PFS. The excellent OS rate observed in the whole group might be the result of a population highly selected for good clinical prognostic factors. Prospective studies of KRAS mutations and sensitivity to chemotherapy are warranted.
Molecular classification based on only four genes identifies basal-like subtypes in high-risk breast cancer patients
Authors: G. Fountzilas, R. M. Wirtz, P. Skarlos, U. Dafni, D. Pectasides, E. Briasoulis, D. Bafaloukos, I. Xanthakis, M. Gehrmann, K. T. Kalogeras
Journal: Journal of Clinical Oncology (2008)

11103 Background: Hormonal receptor status and HER2 over-expression are important prognostic variables in patients with operable breast cancer. The majority of basal-like tumors are triple-negative for estrogen receptors (ER), progesterone (PgR) and HER2 receptors. Such tumors are found in approximately 12% of breast cancer patients and have been shown to have a poor prognosis. Methods: Patients were treated with adjuvant anthracycline-based dose-dense sequential chemotherapy (E-CMF vs. E-T-CMF) in the context of a randomized Phase III study. RNA was isolated from 217 fixed tumor tissue samples employing an experimental method based on magnetic beads from Siemens Medical Solutions Diagnostics, followed by kinetic one-step RT-PCR for mRNA expression analysis. Identification of molecular subtypes was based on 2D hierarchical clustering of four genes. One of these genes (melanophilin, MLPH) is known to be associated with ER1-positive tumors only. Results: Hierarchical clustering based on ER, PgR, HER2, and MLPH mRNA expression identified two groups of low (basal-like, 14+18=32 of 217, 15%) and two groups of high (86 of 217, 40%) mRNA expression. One of the basal-like subtypes (14 of 217, 6%) was found to retain some expression of the HER2, ER and MLPH genes. Patients with basal-like tumors were found to have significantly shorter overall survival (p=0.02) compared to the patients with high mRNA expression. No difference was found in terms of disease-free survival (p=0.373). Interestingly, survival of basal-like patients appears to reach a plateau after the 5th year, with neither recurrences nor deaths being observed during an additional 4 years of follow-up. Conclusions: The results of this study confirm that basal-like patients, identified by only four genes among high-risk breast cancer patients, have a poor prognosis. Confirmation studies are currently been performed by evaluating specific basal-like genes. No significant financial relationships to disclose.
Mortality following hip fractures in men with prostate cancer.
Authors: Mieke Van Hemelrijck, Hans Garmo, Karl Michaelsson, Andreas Thorstenson, Pär Stattin, Olof Akre, Lars Holmberg, Jan Adolfsson
Journal: Journal of Clinical Oncology (2013)

49 Background: Rapid loss of bone-mineral density is a known side-effect of androgen deprivation therapy (ADT) for prostate cancer (PCa). Hip fractures are also independently associated with risk of mortality. To our knowledge few population-based observational studies have yet investigated the risk of dying following fractures among men with PCa. We aimed to assess skeletal-related events and mortality in more detail by specifically studying the link between hip fractures in PCa men and risk of death. Methods: PCBaSe Sweden 2.0 is based on the National Prostate Cancer Register and contains age and county matched men free of PCa. We selected all men (n=14,205) who had been hospitalized with a hip fracture, as registered in the National Patient Register, between 2006 and 2010. A total of 2300 were diagnosed with PCa before the hip fracture and 66% of them were treated with ADT. The main outcome was death as registered in the National Cause of Death Register. The risk of death was estimated using multivariate Cox Proportional Hazards regression analyses and standardized mortality ratios (SMRs) taking into account PCa risk category, history of fractures, civil status, Charlson Comorbidity Index, and treatment with bisphosphonates. Results: In the analysis for risk of death &gt;90 days after a hip fracture, there was an increased risk of death among PCa men on ADT, especially those aged &lt;84 years (e.g., HR at 3-6 months after hip fracture: 2.47 (95%CI: 1.85-3.30) compared to men free of PCa with a hip fracture). The SMRs showed that PCa men on ADT who got a hip fracture were seven times more likely to die than expected in the reference population of all men with PCa, whereas PCa men who were not on ADT and had a hip fracture were 13 times more likely to die than expected in this reference population. However, the absolute risk difference between men with and without a hip fracture was 30 per 1,000 person-years when evaluating the effect of a hip fracturing among men on ADT, whereas a hip fracture would cause an additional 20 per 1,000 person-years to die among PCa men without ADT as well as among men free of PCa. Conclusions: Our SMRs and absolute risk calculations show that hip fractures are more dangerous in PCa men treated with ADT than in PCa men without ADT or in men free of PCa.
Standardized uptake value (SUV) by positron emission tomography/computed tomography (PET/CT) as a prognostic variable in metastatic breast cancer (MBC).
Authors: K. L. Jhaveri, G. Ulaner, M. Fazio, A. Eaton, S. Patil, L. Evangelista, C. Serna-Tamayo, H. L. McArthur, C. Hudis, P. G. Morris
Journal: Journal of Clinical Oncology (2011)

3 Background: The accurate prediction of outcome from MBC could be useful if it could guide more effective therapies. Because PET/CT combines anatomical with functional imaging it could enable greater individualization of treatment. However, there is substantial SUV variation by anatomic site. In this retrospective, single-institution study, we examine baseline SUV on PET/CT as a predictor of outcome from MBC. Methods: Patients (Pts) with ≥1 metastatic lesion on PET/CT performed ≤60 days of diagnosis of MBC from 01/01/2001-12/31/2008 were identified through institutional databases. Pts who rcvd chemotherapy within 30 days prior to PET/CT were excluded. Electronic medical record reports were reviewed and maximum SUV (SUV-MAX) by site for lesions in bone, liver, lung and lymph node (LN) was recorded. In a secondary analysis, PET/CT scans were reviewed and SUV-MAX recalculated. Relationships between SUV-MAX and OS were assessed using Cox regression by site. Results: We identified 285 pts, median (med) age 57 yrs (range 27-90) who had PET/CT at med of 2.3 yrs (range 0–41) from primary BC (67% ER+ and 21% HER2+). Med time between PET/CT and MBC diagnosis was -9 days (range -58–59). At med follow-up of 53 mths, 163 pts have died. Med OS is 41 mths (95%CI 34-48). The SUV-MAX by site was; bone (N=159) med 7.0 (range 2.1–29.6); liver (N=55) med 8.2 (range 2.9–51.2); lung (N=89) med 4.7 (range 1.1–24.0); LN (N=180) med 6.9 (range 1.2–34.0). On univariate analysis, higher SUV in bone was associated with shorter survival (p&lt;0.001; table). This was maintained in multivariate analyses after adjusting for known prognostic variables (p=0.02). A similar trend for shorter survival for higher SUV was noted in liver (p=0.07). However, no relationship between SUV and OS was noted in lung (p =0.34) and LN (p=0.6). Conclusions: This large retrospective study of pts with chemotherapy-naïve MBC suggests that SUV-MAX in bone strongly correlates with prognosis. [Table: see text]
A therapeutic vaccine for nicotine dependence: Results of a phase I and a randomized phase II study
Authors: J. Cornuz, K. Klingler, P. Mueller, F. Jungi, T. Cerny
Journal: Journal of Clinical Oncology (2005)

1008 Background: Tobacco consumption remains the most important avoidable cancer risk and smoking causes 90% of all lung cancers. The vast majority of cigarette smokers who try to quit ultimately fail because of high relapse rates. Clearly novel approaches are needed for the treatment and prevention of nicotine addiction. Cytos002-NicQb is a therapeutic vaccine that aims at induction of nicotine specific antibodies that neutralize nicotine in the blood and reduce nicotine uptake into the brain. In this way nicotine will loose its rewarding central effects. This should enable smokers to break their pattern of addiction and protect them from full relapse in case of occasional ‘slips’. Methods: Phase I: 40 healthy non smokers were included in a single center, randomized, placebo-controlled, parallel-group dose comparison study. Phase II: 300 smokers were included in a multicenter, randomized, double-blind, placebo-controlled efficacy study. Primary endpoint of the study is continuous abstinence from smoking in months 4, 5, and 6 after first vaccination. Continuous abstinence is monitored by self reporting, detection of the nicotine metabolite cotinine in urine samples and by detection of CO in exhaled air. Results: Phase I: Safety: In general, vaccination with NicQb was safe and well tolerated. Of the adverse events that were recorded, most were rated as mild (93%), few as moderate and none as severe. Local reactions were the most prominent side effects observed. Some subjects reported flu-like symptoms. Immunogenicity: All subjects immunized with NicQb showed significant anti-nicotine IgG titers (100% response rate). Phase II: Efficacy: Data will be available in Q2, 2005 and will be presented for the first time at the meeting. Conclusions: NicQb is safe, well tolerated and highly immunogenic. Neutralizing the addiction driving nicotine in cigarette smoke by vaccination of the smoker holds promise to significantly reduce avoidable incidents of cancer and other smoking related disease. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Cytos Biotechnology Cytos Biotechnology Chilka Ltd., Cytos Biotechnology
Outcomes in patients with p0 versus PCIS on final cystectomy pathology.
Authors: Vishnukamal Golla, Ashish M. Kamat, Colin P. N. Dinney, H. Barton Grossman, Jay Bakul Shah
Journal: Journal of Clinical Oncology (2014)

312 Background: For patients with superficial bladder cancer, the presence of Carcinoma in situ (CIS) is known to increase the risk of subsequent upper tract recurrence. In this study, we focused on patients with no residual invasive carcinoma at cystectomy to determine if those patients with pCIS only on final pathology have worse outcomes than patients with p0 bladders. Methods: We performed a retrospective review of our institutional cystectomy database to identify patients with no residual invasive carcinoma on final pathology (p0 or pCIS only). Chi squared test was used to analyze categorical variables and recurrence rates and the Kaplan-Maier method was used to assess the impact of surgical pathology on recurrence-free survival and overall survival over time. Results: Of the 1,897 cystectomy patients in our institutional database, 630 had no residual invasive carcinoma and had complete follow up data. Of these, 285 had stage p0 and 345 had stage pCIS. Local recurrence, upper tract recurrence, and distant recurrence rates were similar between the two groups (p&gt; 0.05 for all). Disease-specific and overall survival rates were also similar for the two groups. In the subset of patients that had received neoadjuvant chemotherapy, there were also no differences in recurrence and survival rates between the p0 and the pCIS groups. Conclusions: The presence of CIS alone in the cystectomy specimen does not increase risk of upper tract recurrence, distant recurrence, or worsened survival compared to patients with p0 bladder pathology. To note there was no financial funding for this study.
Radiolabelled Polymeric Materials for Imaging and Treatment of Cancer: Quo Vadis?
Authors: Kritee Pant, Ondřej Sedláček, Robin A. Nadar, Martin Hrubý, Holger Stephan
Journal: Advanced Healthcare Materials (2017)

Owing to their tunable blood circulation time and suitable plasma stability, polymer-based nanomaterials hold a great potential for designing and utilising multifunctional nanocarriers for efficient imaging and effective treatment of cancer. When tagged with appropriate radionuclides, they may allow for specific detection (diagnosis) as well as the destruction of tumours (therapy) or even customization of materials, aiming to both diagnosis and therapy (theranostic approach). This review provides an overview of recent developments of radiolabelled polymeric nanomaterials (natural and synthetic polymers) for molecular imaging of cancer, specifically, applying nuclear techniques such as positron emission tomography (PET) and single-photon emission computed tomography (SPECT). Different approaches to radiolabel polymers are evaluated from the methodical radiochemical point of view. This includes new bifunctional chelating agents (BFCAs) for radiometals as well as novel labelling methods. Special emphasis is given to eligible strategies employed to evade the mononuclear phagocytic system (MPS) in view of efficient targeting. The discussion encompasses promising strategies currently employed as well as emerging possibilities in radionuclide-based cancer therapy. Key issues involved in the clinical translation of radiolabelled polymers and future scopes of this intriguing research field are also discussed.
Use of calcium and magnesium to prevent oxaliplatin-related neurotoxicity.
Authors: Bernadette Brady, Grainne Cogan, William Grogan, Bryan Hennessy
Journal: Journal of Clinical Oncology (2012)

672 Background: Sensory neurotoxicity is a dose limiting side effect of oxaliplatin. The postulated cause is interference with ionic channels. Calcium and magnesium pre and post oxaliplatin infusion have been suggested to prevent this as they act as chelators. Methods: We performed a review of all patients who were treated with oxaliplatin over a 2 year period. 25 patients received oxaliplatin with calcium gluconate 1g and magnesium sulphate 1g (Ca/Mg group) and 33 did not (no Ca/Mg group). 49 (84%) patients received oxaliplatin as part of the FOLFOX regimen. Other regimens included XELOX, EOX and FLOX. Peripheral neuropathy was defined and graded by the Common Terminology Criteria for Adverse Events v3.0 and was assessed by a clinical nurse specialist (CG). Results: 55 (95%) patients had peripheral neuropathy. There was no significant difference in overall neuropathy and the grade of neuropathy between the Ca/Mg group and no Ca/Mg group. 4 patients required discontinuation of oxaliplatin. One patient (Ca/Mg group) required dose reduction. Patients requiring medical treatment were treated with pregabalin. Conclusions: Oxaliplatin-induced neuropathy is a drug limiting adverse effect. We found that the addition of calcium gluconate and magnesium sulphate did not reduce the incidence or severity of peripheral neuropathy experienced in our cohort. It has been suggested (Park S.B. et al. The Oncologist. 2011;16:708-716) that oxaliplatin induced peripheral neuropathy may not be reversible. This emphasises the importance of managing this difficult symptom appropriately. [Table: see text]