tbuckley/cabot-search huggingface dataset:
Patterns of pelvic recurrence in patients with rectal cancers treated with adjuvant chemotherapy in a multicentre randomised study
Authors: N. Starling, G. Brown, D. Tait, A. Norman, D. Cunningham
Journal: Journal of Clinical Oncology (2005)

3603 Background: Pelvic recurrence is a frequent cause of failure following resection for rectal cancer. Currently there is no universal imaging based classification system for the wide variety in patterns of relapse. Characterisation of these patterns may aid the development of follow up strategies, indicate potential shortcomings of the original local therapy and identify patients suitable for further potentially curative resection or chemoradiotherapy. Methods: Between 1993 and 2003 323 patients with curatively resected stage II and III rectal/rectosigmoid cancer were randomised within a multicentre phase III trial of adjuvant 5-FU and followed up with routine CT scans (chest/abdomen/pelvis). Serial scans of the 61 patients with rectal cancer who developed recurrent disease (median follow up of 55 months) were retrospectively reviewed. 23 (37.7%) developed local only recurrence, 20 (32.8%) had distant only relapse and 18 (29.5%) had both with respective median survivals of 25.5, 24.8 and 21.7 months. 70.5% underwent an anterior resection and 24.6% an abdominoperineal resection. 21.3% received adjuvant radiotherapy and 39.0% had radiotherapy for pelvic relapse. Results: 6 patterns of pelvic recurrence were identified (table below). Combined patterns of relapse were seen in 12/41 rectal relapse patients. Marginal, anastomotic and perineal recurrence are likely to reflect failure of local therapy. Hydronephrosis (associated with peritoneal relapse in 7/9 cases) may be a marker of relapse. Conclusions: We have described 6 patterns of pelvic relapse which could be incorporated into routine surveillance within clinical practice and adjuvant trials. This could facilitate early recognition of relapse, highlight surgery/radiotherapy related failures and guide the development of future neo-adjuvant and adjuvant therapies for patients with resectable rectal cancers. No significant financial relationships to disclose.
Effect of adding sirolimus (s) to imatinib (im) on tumor response following secondary resistance to im in advanced chordoma
Authors: A. Marrari, S. Stacchiotti, F. Crippa, A. Messina, C. Morosi, F. Bozzi, E. Tamborini, A. Gronchi, S. Pilotti, P. G. Casali
Journal: Journal of Clinical Oncology (2008)

10541 Background: IM is active in advanced chordoma, possibly by targeting PDGFRB. Secondary progressions following response have been observed. The evidence of AKT activation in a small group of chordoma patients (pts) prompted us to combine an mTOR inhibitor—sirolimus—to IM in IM-resistant advanced chordoma. Methods: Since July 2007, 7 progressive advanced chordoma patients (F=4, M=3; mean age 53 yrs; PS 0–2) with a secondary resistance to IM and biochemical evidence of AKT expression and activation, have started IM 400 mg/day + sirolimus (2–3 mg/day) on an individual use basis. Sirolimus blood levels were evaluated every 2 weeks. 2 pts were biopsed after 3 months of treatment. Results: Six pts are still on treatment, while one stopped therapy after 3 months for progression. 4 pts are evaluable for response (3 pts too early for response assessment). Treatment was in general well tolerated. The most common side effect requiring treatment discontinuation was G3 leucopenia, with one case of concomitant pneumonia and one case of G3 mucositis. In all cases, pts recovered after stopping treatment. After 4–6 weeks, 3 pts had a PET response (SUV max decrease ≥25%), with subjective improvement and stable disease confirmed on CT/MRI after 3 months of treatment. In one pt, an ulcerated lesion shrunk in a few weeks. Post- treatment AKT assessment in pts undergoing biopsy is under evaluation. Conclusions: In 3 out of 4 evaluable advanced chordoma pts progressing on IM, tumor response was re-established by adding sirolimus to IM. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GlaxoSmithKline, MedImmune, Novartis, Pfizer Oncology, sanofi-aventis Novartis, PharmaMar, SigmaTau Jansen Cilag, Novartis, Pfizer Oncology, Sigma Tau Novartis, PharmaMar
Captopril reverses high-glucose-induced growth effects on LLC-PK1 cells partly by decreasing transforming growth factor-beta receptor protein expressions.
Authors: J Y Guh, M L Yang, Y L Yang, C C Chang, L Y Chuang
Journal: Journal of the American Society of Nephrology (1996)

Transforming growth factor beta (TGF-beta) may be important in the pathogenesis of diabetic nephropathy, and captopril is effective in treating this disorder. However, the mechanisms of this therapeutic effect as related to TGF-beta and its receptors are not known. Thus, the effects of captopril on cellular growth, TGF-beta 1, and TGF-beta receptors were studied in LLC-PK1 cells cultured in normal (11 mM) or high glucose (27.5 mM). This study found that glucose dose-dependently inhibited cellular mitogenesis while inducing hypertrophy in these cells at 72 h of culture, concomitantly with enhanced TGF-beta 1 messenger RNA (mRNA) and TGF-beta receptor Types I and II protein expressions. Captopril dose-dependently (0.1 to 10 mM) increased cellular mitogenesis and inhibited hypertrophy in these cells. Moreover, captopril also decreased TGF-beta receptor Types I and II protein expressions dose-dependently. However, TGF-beta 1 mRNA was not affected by captopril. It was concluded that high glucose decreased cellular mitogenesis while increasing hypertrophy concomitantly with increased TGF-beta 1 mRNA and TGF-beta receptors in LLC-PK1 cells. Captopril can reverse high-glucose-induced growth effects by decreasing TGF-beta receptor protein expressions.
Vinorelbine (NVB)-carboplatin (CBDCA) vs non-platinum doublets in inoperable non-small cell lung cancer (NSCLC) patients (pts)-final results of the Glob 2 phase III with patient benefit analysis
Authors: R. P. Abratt, A. Szczesna, K. Mattson, M. Wernli, P. Reiterer, R. Hui, J. Lizon, O. Bertetto, M. Reck, E. H. Tan
Journal: Journal of Clinical Oncology (2004)

7016 Background: NVB-CDDP is used as a standard regimen for pts with NSCLC. Regimens in which CDDP is replaced by CBDCA or a non Platinum (P) cytotoxic, may result in more favourable tolerance and convenience This phase III was set up to compare a P based regimen (NVB-CBDCA) to a non-P based regimen (NVB-GEM). Methods: Inoperable NSCLC pts were randomly assigned to q3w cy in Arm A (A): NVB 30 mg/m2 at D1,8+CBDCA AUC 5 at D1 or Arm B (B): NVB 25 mg/m2+GEM 1000 mg/m2 both given at D1,8 with 150 evaluable pts planned in each arm. Objective response (OR) was the primary endpoint with secondary end points being time related parameters/tolerance and clinical benefit evaluated on 6 cancer symptoms evolution taking into account weight and PS changes. Results: 316 pts were recruited in 2 yrs in 31 centres with 159 pts in A and 157 in B. Groups were well balanced with same median age: 60/59y, KPS: 90–100 in 63/69%. In both arms pts were metastatic at inclusion in 80%. A median number of 4 cy was given. Median RDI for NVB was 91% (A) and 94% (B) with median RDI for CBDCA at 94% and GEM at 93%. OR in ITT after review was 20.8% (DC=66%) in A vs 28% (DC=72.6%) in B (p=0.15). At the cut-off date (April 1st, 2003), median follow-up was 21.5 m with 128/110 deaths in A/B. MS was 8.6m for A vs 11.5m for B with 1 year survival respectively at 34.4% and 48.9% (p=0.01) and PFS at 3.9 and 4.4m. Main gr3–4 haematological AEs by pts in A/B, were: neutropenia in 44.5/23.4% and significantly more febrile neutropenia in A (17pts/19cy) vs B (1pt/1cy) with 4/0 toxic deaths respectively. There were less gr3–4 non-hematological tox reported in B. Regarding clinical benefit, fatigue, appetite, cough and dyspnea improvement were better in B. Chest pain and hemoptysis improvement were similar in both arms. Mean weight was stable in both. On 111 evaluable pts for the clinical benefit in A, response rate was 32.4% compared to 40.9% (p=0.19) in 110 evaluable pts in B. Conclusions: NVB-GEM given as a non-P doublet in this phase III has demonstrated OR, PFS and clinical benefit comparable to NVB–CBDCA doublet with a favorable MS and tolerance profile. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre
Prospective Randomised Trial Comparing Protracted Iv 5fu Infusion Alone Or With Hepatic Intra-arterial Injection of Yttrium-90 Resin Microspheres for Patients With Liver-limited Metastatic Colorectal Cancer Refractory To Standard Chemotherapy
Authors: P. Flamen, Marc Van den Eynde, Marie-Rose Peeters, L. Defreyne, G. Maleux, J. Vannoote, Pierre Delatte, M. Paesmans, J. Van Laethem, A. Hendlisz
Journal: Annals of Oncology (2010)
Safety and efficacy analysis of sunitinib (S), bevacizumab (B), and M-Tor inhibitors in metastatic renal cell cancer (mRCC) patients (pts) with renal insufficiency (RI)
Authors: S. Gupta, V. Parsa, L. Heilbrun, D. Smith, B. Dickow, E. Heath, U. Vaishampayan
Journal: Journal of Clinical Oncology (2009)

5108 Background: S, T (temsirolimus) and E (everolimus) are primarily metabolized in the liver, while the metabolism of B is unclear. There are limited data on the clinical toxicity profile and efficacy of these agents in pts with RI. Methods: The primary objective was to assess the safety and efficacy of S, B, T and E in pts with RI. Medical records of pts with mRCC at Wayne State University, treated on S, B, T or E were reviewed. Pts with a calculated creatinine clearance (CrCl) of ≤ 60ml/min [chronic kidney disease stage 3 or higher per K/DOQI guidelines by the National Kidney Foundation] were deemed to have RI. Data on safety and efficacy of the therapy were collected and analyzed with respect to renal function. Results: 19 of 51 (37%) pts had RI. Pts with RI had a higher median rise in blood pressure (BP) with S and B than pts with normal renal function. Patients with RI had an increased incidence of rash and higher dose interruption rates with m-TOR inhibitors. No major differences in toxicities including cardiac, thyroid, renal, lipid profile abnormalities or hyperglycemia were observed. Similar efficacy was seen in all groups. Conclusions: More than a third of pts with mRCC receiving targeted therapy have RI, hence highlighting the importance of evaluating tolerability of therapies in pts with RI. Therapy with S, B and T/E is well tolerated and efficacy appears to be maintained. Closer monitoring for hypertension is needed in pts receiving S and B. [Table: see text] No significant financial relationships to disclose.
A non-randomized phase II study of sequential irinotecan (CPT) and flavopiridol (F) in patients (pts) with advanced hepatocellular carcinoma (HCC)
Authors: G. K. Abou-Alfa, R. D. Carvajal, K. Y. Chung, R. A. Ghossein, M. Capanu, M. Gonen, G. Jacobs, D. P. Kelsen, G. K. Schwartz
Journal: Journal of Clinical Oncology (2006)

4148 Background: F is a CDK inhibitor which potentiates CPT- induced apoptosis. In a phase I trial of CPT 100mg/m 2 followed 7 hours later by F given over 1 hour weekly for 4 out of 6 weeks (Shah, Clin Can Res 2005), 2 pts with advanced HCC had stable disease (SD) for 14+ months. In the same phase I study, patients who were p53 wild-type (negative p53 staining), and whose p21 remained stable or was non-detectable on the post-treatment biopsy, were noted to have SD or a partial response. Methods: Pts with advanced HCC, no prior systemic therapy, Child’s-Pugh score A, B7 or B8, and KPS ≥ 70%, received 100 mg/m 2 of CPT, followed 7 hours later by 60 mg/m 2 of F over 1 hour weekly for 4 out of 6 weeks. The trial had a two stage design, with a planned accrual of 30 pts. The primary endpoint was TTP. Tumor response was assessed every 2 cycles using revised WHO criteria. p53 immuno-staining was performed on pre-treatment paraffin preserved tissues. A cut-off of 20% defined positive mutant versus negative wild-type p53 status. Results: 16 pts were enrolled: median age 64 (range 26–84), KPS 80% (70–90%), and 10 males/6 females. 13 pts received therapy, two progressed before starting, and one patient (pt) was excluded because pathology re-review did not confirm HCC. 1 pt was excluded because of consent withdrawal after first dose of therapy. This pt was included in the toxicity analysis. The median number of cycles given was 2 (range 1–8 cycles). Grade 3 and 4 toxicities included dehydration (4: 30%) diarrhea (2: 15%) febrile neutropenia (6: 46% - 4 events in one pt) and fatigue/weakness (3: 23%). Therapy had to be discontinued in 2 pts because of toxicity. TTP was 2.6 months (95% CI 2.43–8.42). One patient had SD for over a year, 8 had progression of disease (POD), and 4 came off study because of toxicity. Mutational p53 was evaluated in 7 pts. The pt with SD had wild type p53. Three pts with POD had mutant p53, while the other 3 had wild type 53. Conclusions: CPT followed by F is an ineffective therapy for HCC. This therapy was relatively poorly tolerated, likely contributed to by underlying cirrhosis in HCC, but similar to our experience of CPT in HCC. While p21 level pre and post therapy is lacking, the wild type p53 of the patient with SD maybe a predictor of response in HCC where p53 mutations are common. No significant financial relationships to disclose.
Survivorship: An unmet need of the patient with cancer - implications of a survey of the Lance Armstrong Foundation (LAF)
Authors: S. N. Wolff, C. Nichols, D. Ulman, A. Miller, S. Kho, D. Lofye, M. Milford, D. Tracy, B. Bellavia, L. Armstrong
Journal: Journal of Clinical Oncology (2005)

6032 Background: The diagnosis and treatment of cancer causes substantial physiologic and psychosocial effects for many of the estimated 10 million people currently living with a history of cancer. This burden, noted as survivorship, begins at diagnosis and continues well after the conclusion of active anti-cancer therapy. To better understand the magnitude, affect and implications to the health care system, the LAF (www.laf.org) performed a large-scale internet-based cohort study. The LAF, working with Public Strategies, Inc. and SS+K, conducted an 83 question quantitative poll of 1,020 self-identified cancer survivors from October 1–6, 2004. The survey was conducted among a randomly selected sample of cancer survivors using e-Rewards’ online panel. Respondents were sent an e-mail invitation containing a link to participate in the survey. The margin of error for the survey is ±3.1% at the 95% CI. The data presented represents preliminary summation of the survey with each question having more detailed information. Results: The following table summarizes key aspects of the survey with other questions analyzed but not reported. Conclusion: The survey highlights that there are serious, frequent and unmet medical and non-medical needs for patients during and after their treatment of cancer. These include psychological and financial issues that are currently not being addressed due to non-recognition or a lack of available physician skills or resources. The results of this survey have implications to the medical community that indicate that a more rigorous detailed analysis and understanding of survivorship issues is required to best meet these needs and improve the well-being of patients with cancer. No significant financial relationships to disclose.
Insulin-like growth factor-1 induces adhesion and migration in human multiple myeloma cells via activation of b1-integrin and phosphatidylinositol 3-kinase/AKT signaling beta.
Authors: YT Tai, K Podar, L Catley, YH Tseng, R Shringarpure, R Burger, M Akiyama, T Hideshima, D Chauhan, N Mitsiades, P Richardson, NC Munshi, CR Kahn, C Mitsiades, KC Anderson
Journal: Blood (2003)
Imaging results after CHOP-rituximab followed by <sup>90</sup>Y ibritumomab tiuxetan and rituximab (R) in patients with previously-untreated follicular lymphoma (FL)
Authors: N. A. Demonaco, M. Wu, J. Osborn, T. Evans, K. A. Foon, S. Swerdlow, J. Kant, J. Joyce, S. Land, S. A. Jacobs
Journal: Journal of Clinical Oncology (2006)

7589 Background: There has been some question regarding the predictive value of 111 In scans in FL. We report imaging results with fusion PET-CT scans and 111 In scans in a single-institution, non-randomized, phase II trial in patients with FL treated with CHOP-R followed by 90 Y ibritumomab tiuxetan (Zevalin (Z)) and R. Methods: Eligible patients have CD20 positive FL, Grade 1–3 or transformed, Stage II-IV, no prior treatment with monoclonal antibody or chemotherapy, and symptomatic disease (if grade 1–2). CHOP-R is given every 21 days for 3 cycles. Four weeks after the last dose of CHOP-R, patients receive the Zevalin regimen, which includes 111 In imaging and 90 Y therapy. One week after Z, patients receive R 375 mg/m 2 IV weekly for 4 doses. Bone marrow examination and fusion PET-CT scans are performed at baseline, after CHOP-R, and 12 weeks after Z. The primary endpoint is CR, and responses are reported using the International Working Group (IWG) criteria with the additional requirement of a negative PET scan for CR/CRu. Results: Thirty-six FL patients have been accrued, and 16 patients have completed therapy and follow-up studies. One patient did not have a positive PET scan at baseline. Following therapy, the proportion with a negative PET scan improved from 8 of 15 (53.3%) after CHOP-R to 15 of 15 (100%) after Z. Using IWG criteria in combination with PET scan results, the CR rate increased from 4 of 15 (26.7%) after CHOP-R to 12 of 15 (80%) after Z. Five of 6 patients (83%) with tumor uptake by 111 In scan and 7 of 9 (78%) with a 111 In scan negative for tumor achieved a CR. Conclusions: There was no significant difference in CR between those patients with 111 In tumor uptake versus patients with a negative 111 In scan. Functional imaging with PET-CT may be a more sensitive method than CT alone in determining residual disease in FL. This trial continues to accrue patients, and more time is needed to determine the duration of response and time to next therapy. No significant financial relationships to disclose.
Meta-analyses of randomized trials assessing the interest of postoperative adjuvant chemotherapy in gastric cancer
Authors: J. Sakamoto, X. Paoletti
Journal: Journal of Clinical Oncology (2008)

4543 Background: Despite potentially curative resection of stomach cancer, 50%-90% of patients die of disease relapse. Despite numerous encouraging phase II and phase III trials comparing surgery alone (S) to adjuvant chemotherapy (S+CT), definitive evidence is lacking. Only S1 has shown significant results in terms of overall survival (OS). Our group has initiated an individual patient data (IPD)-based meta-analysis of all randomized clinical trials (RCTs) in the adjuvant gastric setting to quantify the potential benefit of S+CT over S and to further study the role of various treatments including mono-chemotherapy, combined chemotherapy with FU derivatives, mitomycin-C (MMC), anthracyclines, taxanes, or irinotecan. Methods: All RCTs closed to patient accrual at the end of 2003 were eligible. Trials with radiotherapy, intraperitoneal chemotherapy, or immunotherapy were excluded. The primary endpoint was OS, the secondary endpoint disease- free-survival. The logrank-test was stratified by trial. Data collection was initiated in January 2007. Results: Thirty-one eligible RCTs (6,666 patients) were identified. As of December 2007, IPD were available from 14 trials (3,293 patients) with a median follow-up exceeding 8 years. There was an overall statistically significant OS benefit in favour of CT+S (HR=0.81, 95% CI 0.73–0.89, p <0.0001). There was no significant heterogeneity across RCTs (p=0.25). Based on 1053 patients (3 studies), CT including 5-FU and MMC without anthracyclines was associated to survival benefit as compared to surgery alone (HR=0.74, 95% CI 0.58–0.95, p=0.02). CT including anthracyclines led to a similar improvement (HR=0.74, 95% CI 0.63–0.88, p<0.001) in 4 RCTs with 836 patients. Conclusions: IPD-based meta-analysis represents one of the highest levels of evidence. Our study has already collected more data than presented in the previous exhaustive literature review. Our interim results show a modest but significant overall survival benefit in favour of adjuvant chemotherapy, with or without anthracyclines, over surgery alone. No significant financial relationships to disclose.
Changes in survival in head and neck cancers in the late twentieth and early twenty-first centuries: A period analysis.
Authors: H. Brenner, S. B. Chalasani, D. Pulte
Journal: Journal of Clinical Oncology (2010)

e12011 Background: Therapy for head and neck cancers has evolved over the past decade but few detailed analyses of recent developments in survival on the population level have been published. Methods: We use period analysis and modelled period analysis to disclose recent trends in survival in patients with head and neck cancer. Data is derived from the Surveillance, Epidemiology and End Results limited use database. Results: Major statistically significant improvement in survival was observed, with overall 5-year relative survival going from 54.7% in 1992-96 to 65.9% in 2002-06. Subgroup analysis showed improvement in cancers of the oral cavity, tongue, tonsils, and nasopharynx with the greatest improvements observed in tonsillar carcinoma (+22.2 percentage points) and carcinoma of the tongue (+14.4 percentage points). Further analysis of survival for oral cavity, tonsillar and tongue carcinoma revealed improvements in survival at each stage and across all age groups except for patients greater than 75 years with the greatest improvement occurring in locally advanced disease and patients aged 55-64 for carcinoma of the tongue and tonsils and 15-44 for oral cavity cancers. Conclusions: Survival has substantially improved for head and neck cancers over the past decade. The greatest improvement was seen in tonsillar and tongue cancers. These changes most likely reflect both improved therapeutic options and increased incidence of human papilloma virus associated cancers. Five-year relative survival rates for head and neck cancers 1992-1996 to 2002-2006 Location Calendar period 1992-1996 PE (SE) 1997-2001 PE (SE) 2002-2006 PE (SE) Diff* p value** All 54.7 (0.5) 58.6 (0.5) 65.9 (0.5) +11.2 <0.0001 Lip 95.5 (1.4) 90.9 (1.5) 97.4 (1.7) +1.9 0.5 Tongue 50.5 (1.2) 55.6 (1.1) 64.9 (1.0) +14.4 <0.0001 Oral cavity 51.1 (1.0) 56.6 (1.1) 62.9 (1.2) +11.8 <0.0001 Nasopharynx 53.8 (2.1) 58.3 (1.9) 62.3 (1.9) +8.3 0.002 Tonsil 47.6 (1.7) 56.5 (1.5) 69.8 (1.3) +22.2 <0.0001 Oropharynx 33.3 (3.2) 37.8 (3.1) 42.2 (3.1) +8.9 0.2 Hypopharynx 29.8 (1.6) 29.7 (1.6) 33.8 (2.0) +4.0 0.3 Abbreviations: PE, period estimate; SE, standard error. * Difference between values in 1992-1996 versus 2002-2006. ** p value for trend 1992-1996 to 2002-2006. No significant financial relationships to disclose.