tbuckley/cabot-search huggingface dataset:
Initial phase II results of SGN-30 (anti-CD30 monoclonal antibody) in patients with refractory or recurrent systemic anaplastic large cell lymphoma (ALCL)
Authors: A. Forero, S. Bernstein, A. Gopal, F. Foss, J. Leonard, N. Bartlett, B. Cheson, J. Barton
Journal: Journal of Clinical Oncology (2005)

6601 Background: SGN-30 is a chimeric monoclonal antibody (mAb) directed against the CD30 antigen expressed on hematologic malignancies. SGN-30 was well tolerated in phase I and objective responses were seen. Methods: Refractory or recurrent CD30 positive ALCL patients, ECOG performance status 0–2, are treated in a multicenter, single arm phase II study. SGN-30 at 6 mg/kg is administered by short IV infusion weekly for 6 consecutive doses. A two stage statistical design provides a 90% power to detect an objective tumor response rate of at least 30%. Results: Patient Characteristics: 8 patients (3 male, 5 female) with median age 59 years have been enrolled. Median number of prior therapies is 2.5 (range 1–5). 88% of patients have received prior CHOP. Efficacy: 6 patients are evaluable for efficacy with 1 CR, 1 PR, 1 SD and 3 PD. The patient with a CR had a chest wall mass measuring 5.1 x 2.0 cm which disappeared completely after 6 doses of SGN-30. The duration of the CR is 49+ days. The patient with a PR had extensive cutaneous and nodal disease and constitutional symptoms. After treatment there was resolution of all skin lesions, reduction in lymphadenopathy and improvement in the constitutional symptoms. Assessment of duration of response was not possible as the protocol (subsequently amended) did not permit further therapy and the patient was switched to chemotherapy after 28 days. Tolerability: The most common adverse events included cough, diarrhea, fatigue, hoarseness, muscle weakness, rigors and vomiting. Each occurred in at least 2 patients. Only one grade 3/4 adverse event of catheter related infection was thought possibly related to SGN-30. Conclusions: The drug is well tolerated and shows signs of antitumor activity. Recruitment into the study continues. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Seattle Genetics Seattle Genetics
Prevention of endothelial dysfunction in heart failure by vitamin E Attenuation of vascular superoxide anion formation and increase in soluble guanylyl cyclase expression
Authors: J Bauersachs
Journal: Cardiovascular Research (2001)

Objectives: Enhanced vascular superoxide anion generation contributes to endothelial dysfunction in heart failure. However, the effect of long-term treatment with the antioxidant vitamin E is unknown. Methods and Results: Relaxant responses were determined in aortic rings from Wistar rats with heart failure 12 weeks after myocardial infarction (MI) and compared with responses in tissues from sham-operated animals. From the seventh post-operative day, rats were given either a standard chow or a chow enriched in vitamin E (approximate intake 100 mg/day). In rings from rats with heart failure, acetylcholine-induced relaxation was attenuated (maximum relaxation, Rmax 54±3%) when compared with rings from sham-operated animals (79±3%, n=12, P<0.01), while endothelium-independent relaxation elicited by sodium-nitroprusside was unchanged. Aortic superoxide generation was significantly enhanced in rats with heart failure. Vitamin E supplementation significantly improved acetylcholine-induced relaxation in rats with heart failure (Rmax 75±4%, P<0.01) and led to a leftward shift in sodium-nitroprusside-induced relaxation curve. Aortic expression of the β1-subunit of soluble guanylyl cyclase was significantly enhanced by vitamin E supplementation. In addition, the elevated vascular superoxide formation was normalised by vitamin E. Conclusions: These results demonstrate that dietary supplementation with the antioxidant vitamin E restores normal endothelial function, reduces vascular superoxide anion formation and increases the expression of the soluble guanylyl cyclase in rats with heart failure.
The next step towards rational treatment for ‘The sportsman's groin’
Authors: Aali J Sheen, Hannu Paajanen
Journal: British Journal of Sports Medicine (2015)

It is well recognised that for over three decades the aetiology, whether of hip or adductor, or groin related, and subsequent management, whether surgical or otherwise, of ‘sportsman's groin’ remains mainly controversial with the literature reporting mainly case series with a few randomised trials comparing differing treatment modalities and offering some anecdotal evidence. Eventually, in 2014, the world's first consensus statement was published, which has bravely attempted to define a condition where no true hernia exists but that is a perceived repetitive strain injury causing inguinal pain and/or disruption.1

The literature to date does report some prospective randomised data on open and laparoscopic surgical results, in comparison to active physiotherapy and other conservative measures, however, there are few high-quality studies, as reported by Serner et al , with surgery not figuring high on the treatment agenda.2–4

Some of these trials do, however, appear to demonstrate a distinct leaning towards surgical repair of the disrupted groin and associated chronic pain as the treatment of choice. The surgical repair technique used, though, has largely been an example on the expertise available in the respective units carrying out such repairs. This rationale is ever apparent, as no real study from any ‘sports groin’ unit has reported on more than one type of procedure being undertaken for inguinal-related groin pain or …
Expression changes of angiogenic factors in rectal carcinomas after neoadjuvant chemoradiotherapy.
Authors: S. Bae, M. Baek, D. Jeong, C. Kim, E. Kim, E. Shin, D. Park
Journal: Journal of Clinical Oncology (2010)

e14061 Background: Preoperative chemoradiotherapy followed by a complete tumor resection is a well-established treatment strategy for locally advanced rectal cancer. Angiogenesis is important prognostic factors in rectal cancer. Neoadjuvant chemoradiotherapy can change the angiogenic factor expression profiles of rectal cancer. However, little is known about its possible changes in response to preoperative chemoradiotherapy. We examined the angiogenic factor expression profiles of rectal cancer tissues before and after neoadjuvant chemoradiotherapy in patients with rectal carcinoma. Methods: Fifty eight patients with locally advanced rectal cancer were studied. All patients were given preoperative chemoradiotherapy of 5,040 cGy for 5–6 weeks with concurrent administration of 5-fluorouracil and leucovorin. Surgical resection was performed 6–8 weeks later in all patients. Immunohistochemical staining for angiogenenic factors (vascular endothelial growth factor, placenta growth factor, hypoxia inducible factor 1α, stromal derived factor 1α) were performed on specimens obtained before preoperative chemoradiotherapy and after surgery. A semiquantitative-immunohistochemical score established from the extension and intensity of the angiogenic factors was used for analysis. Results: Neoadjuvant chemoradiotherapy downregulated VEGF protein expression in the rectal cancer tissues and led to a lower PlGF, HIF 1α protein expression in rectal cancer tissues (p < 0.01). However, neoadjuvant chemoradiotherapy upregulated SDF 1α protein expression in rectal cancer tissues. (p < 0.03). And also, higher SDF 1α protein expression after neoadjuvant chemoradiotherapy significantly associated with advanced TNM stage. However, those data show no correlation between the levels of expression and the histology, or tumor size. Conclusions: Our results reveal that stromal cell–derived factor 1α (SDF-1α) was up-regulated and VEGF, PlGF, HIF 1α downregulated in rectal cancer tissues after preoperative chemoradiotherapy. Our data suggests that neoadjuvant chemoradiotherapy could up-regulate angiogenic factor SDF 1α, which should be evaluated as new targets for antiangiogenic therapy. No significant financial relationships to disclose.
Acute and late effects of radical radiotherapy in elderly head and neck cancer patients
Authors: A. Turaka, B. K. Mohanti, S. Chander, R. Jena, S. V. Deo
Journal: Journal of Clinical Oncology (2007)

16515 Background: To evaluate the difference between acute and late effects of radical radiotherapy in elderly(above 60 years,Group A) head and neck cancer patients with young patients (below 50 years of age, Group B). Methods: The study was conducted on histologically proven head and neck cancer patients receiving radical radiotherapy (RT),49 patients were in group A and 40 in group B.The acute and late radiation morbidity was assessed using RTOG (phases I,II,&amp;III- Pre RT, During RT &amp; 1 month post RT respectively) and LENT-SOMA scoring systems (phases IV &amp;V-3 &amp; 6 months post RT). Results: In phase II, grade I dermatitis was commonly seen (83.7% in group A,72.5% in group B) and grade II dermatitis was 12.2 % vs 25% of patients.The difference in distribution over age was not significant (p= 0.12 &amp; 0.18 in phase II and III).There was no significant difference in the incidence of late effects between two groups (p=0.91 in phase IV and p=0.99 in phase V).Grade II mucositits was seen in majority of patients in both groups,71.4% vs 72.5% in phase II.The late mucosal changes with worrisome subjective (pain) experiences were observed in 69.4% vs 75% of patients in group A and B, respectively.The difference in distribution over the age was significant (p&lt;0.051) only in phase II.Dryness of mouth was the most common acute and late sequel of RT.The acute salivary gland morbidity was mostly moderate to complete dryness (grade II),seen in phases II and III in 24.5% &amp; 73.5% of patients but the late sequel was seen in 83.37% of patients in group A and 85% in group B and the difference in late effects in both groups was statistically significant except in phase V (p= 0.02). Moderate dysphagia of grade II morbidity was seen in 75.5% vs. 65% in phase II. Grade III dysphagia was seen only 5 patients in group A and one in group B. In phase IV,66.7% patients in group A,72.5% in group B had persistent difficulty in swallowing. Conclusions: Grade I and II mucositis and dermatitis during the course of treatment led to increased morbidity, decreased nutritional intake and pain. Xerostomia is the most common and inevitable acute and late squeal of radical radiotherapy to head and neck cancer region resulting in difficulty in mastication and swallowing. There was no difference in the occurrence of acute and late effects between younger and elderly patients. No significant financial relationships to disclose.
QUASAR: A randomized study of adjuvant chemotherapy (CT) vs observation including 3238 colorectal cancer patients
Authors: R. G. Gray, J. Barnwell, R. Hills, C. McConkey, N. Williams, D. Kerr
Journal: Journal of Clinical Oncology (2004)

3501 Background: The size of survival benefit from adjuvant fluorouracil/folinic acid (FUFA) CT for colorectal cancer is unclear. Methods: Patients with apparently curative resections of colon or rectal cancer were randomized following surgery between FUFA and observation (with CT considered on recurrence). CT consisted of either six 5-day, four-weekly or 30 once-weekly courses of intravenous fluorouracil (370mg/m2) with either high-dose (175mg) or low-dose (25mg) L-folinic acid, and with either levamisole or placebo. Primary outcome was all cause mortality. Results: Between June 1994 and December 2003, 3238 patients (91% Dukes B, 71% colon cancer, median age 63) from 150 centres in 17 countries were randomised. Direct randomised comparisons found no benefit for high-dose FA or levamisole (Lancet 2000;355:1588–1596). A non-randomised comparison suggested equal efficacy but less toxicity with the once-weekly schedule (Annals of Oncology 2000;11:947–955). With a median follow-up of 4.2 years, risk of death with CT vs control was 0.88 (95%CI 0.75–1.05; p=0.15) and recurrence 0.82 (0.70–0-97; p=0.02). Treatment efficacy did not differ significantly by stage, site or age but efficacy of the 4-weekly schedule was significantly (p=0.04) greater than once-weekly -a prior hypothesis. Conclusions: Chemotherapy produces a small (1% - 5%) survival benefit for stage B patients, sufficient to outweigh the inconvenience and cost for high-risk and younger patients. Longer follow-up and meta-analysis of all trials is needed to clarify the balance of benefits and disbenefits for older patients. No significant financial relationships to disclose.
Everolimus for subependymal giant-cell astrocytomas (SEGAs) in tuberous sclerosis (TS).
Authors: D. N. Franz, D. A. Krueger, M. M. Care, K. Holland-Bouley, K. Agricola, C. Tudor, P. Mangeshkar, A. W. Byars, T. Sahmoud
Journal: Journal of Clinical Oncology (2010)

2004 Background: TS is a potentially devastating disorder characterized by hamartoma formation in multiple organ systems. SEGAs develop in 5-15% of TS patients and represent a significant medical risk, including the potential for sudden death secondary to acute hydrocephalus (as a result of their location adjacent to the foramen of Monro). Neurosurgical resection is the current standard treatment and no effective alternative has been identified. Methods: Patients ≥3 years with a definitive TS diagnosis and evidence of serial SEGA growth (on MRI) were eligible for this prospective, open-label, phase II study. The primary efficacy endpoint was change in SEGA volume from baseline to 6 months (mo). Everolimus dose (3 mg/m2 QD orally) was titrated subject to tolerability to achieve target trough concentrations of 5-15 ng/mL. Results: 28 patients were enrolled between 1/07 and 12/08; median duration of treatment was 22 mo (range 5-34). Everolimus was associated with a clinically meaningful reduction in SEGA volume (p<0.001); marked reductions were seen within the initial 3 mo and subsequently sustained or further improved (see table). No patient developed new lesions, worsening hydrocephalus, or worsening signs or symptoms of increased intracranial pressure; none required surgical resection or other therapy for SEGA. Of 16 patients for whom video-EEG data were available, 9 experienced decreases in seizure frequency (across all types of seizure), 6 reported no change (all were event-free at both timepoints), and 1 patient experienced an increase (median change -1.0, p=0.012). Grade 3 adverse drug reactions were single cases of sinusitis, pneumonia, viral bronchitis, tooth infection, stomatitis, and leukopenia; no grade 4 events were reported. Conclusions: Everolimus is effective in TS-associated SEGA with 78% of patients achieving the prespecified ≥30% reduction at 6 mo; it is also well tolerated and offers a viable alternative to surgical resection. SEGA volume (independent central review) % reduction from baseline, n (%) 3 mo n=26 6 mo n=27 12 mo n=26 18 mo n=18 24 mo n=8 ≥50% 10 (38) 9 (33) 9 (35) 8 (44) 3 (38) ≥30% 17 (65) 21 (78) 20 (77) 12 (67) 6 (75) >0% 25 (96) 27 (100) 26 (100) 16 (89) 8 (100) No change 0 0 0 1 (6) 0 Growth 1 (4) 0 0 1 (6) 0 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Novartis Novartis Novartis Novartis Novartis
Predictive testing for erythropoietin induced tumor progression in head and neck cancer
Authors: C. A. Blau, C. P. Miller, K. A. Lowe, D. Mattern, K. Valliant-Saunders, N. Urban, M. Henke
Journal: Journal of Clinical Oncology (2008)

11007 Background: Although anemia is an independent poor prognostic factor in cancer, its correction using erythropoietin (Epo) may promote cancer progression and reduce survival, as suggested by several recent Phase III trials. We tested whether measuring Epo receptor (EpoR) mRNA levels in head and neck cancer could identify patients susceptible to Epo induced tumor growth. We also examined whether endogenous Epo might stimulate tumor growth. Methods: We measured EpoR mRNA levels in tumors from a previously reported Phase III trial in which 351 patients irradiated for head and neck cancer were randomized to Epo or placebo (Henke et al., Lancet 2003). 154 of these tumors had been evaluated previously with a polyclonal antibody raised against the human EpoR (C20) (Henke et al., J Clin Oncol 2006), but which also cross reacts with non-EpoR proteins (Elliott et al., Blood 2006). EpoR mRNA levels were measured in 106 tumors. We examined the relationship between EpoR mRNA level and locoregional progression free survival (LPFS), the primary study endpoint, in subjects assigned to Epo versus placebo. For patients enrolled in the placebo arm we also compared baseline serum Epo levels, C20 status, EpoR mRNA levels, and LPFS. Results: Epo-treated patients with unresected tumors that expressed above-median EpoR mRNA levels experienced a reduction in LPFS compared to the placebo group (p=0.02, n=s effect was not observed in patients with unresected tumors that expressed below-median EpoR mRNA levels (p=0.80, n=14). EpoR mRNA levels had no effect in patients with completely resected or partially resected tumors. In placebo patients with unresected or incompletely resected tumors, increased Epo levels were associated with impaired LPFS if their tumors were C20 positive (p=0.02, n=22), and improved LPFS if their tumors were C20 negative (p=0.09, n=15). C20 status and EpoR mRNA levels did not correlate (r=−0.11). Conclusion: Adverse effects of Epo on tumor progression may depend on tumor EpoR expression. Whether a relationship exists between other C20 targets and Epo induced tumor progression deserves further exploration. Our findings present clear hypotheses that should be tested in archival tumors from other Phase III trials. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Hoffman-La Roche
A comparison of the outcomes after neoadjuvant (NC) or adjuvant chemotherapy (AC) for muscle-invasive urothelial bladder cancer (UC): A French contemporary retrospective multicenter cohort.
Authors: Damien Pouessel, Sylvie Chevret, Guilhem Roubaud, Safae Aarab-Terrisse, Christine Chevreau, Dimitri Vordos, Frederic Rolland, Laurys Boudin, Florence Joly, Charlotte Joly, Philippe Beuzeboc, Helen Jane Boyle, Delphine Farneti, Jérôme Dauba, Guillaume Moriceau, Ingrid Alexandre, Gael Deplanque, Yohann Loriot, Nadine Houede, Stephane Culine
Journal: Journal of Clinical Oncology (2015)

325 Background: Our aim was to investigate outcome of patients (pts) treated with AC or NC for organ-confined UC, or with NC for clinical lymph node involvement (cN+). Methods: We retrospectively analyzed 482 pts treated in 22 French hospitals between 2000 and 2013 in 3 settings: 226 pts with radical cystectomy (RC) and AC (AC group), 193 cN0 (NC group), and 63 cN+ (cN+ group) pts received NC before a planned RC for cT2-T4, M0 UC. The primary outcome was overall survival (OS). Cancer-related survival (CRS) was also evaluated. Multivariate Cox proportional hazards regression was used to estimate adjusted hazard ratios with 95% confidence interval. Results: Median age was 62, 61.7, and 62.1 in AC, NC, and cN+, respectively. Median time between diagnosis and first treatment (RC or NC) was 2.1, 1.4 and 1.6 months, respectively (p&lt;0.001). In AC, stages were p≤T2 (n=46) or pT≥3 (n=180), pN0 (n=37), pN+ (n=168), or pNx (n=21). Gemcitabine-cisplatin and gemcitabine-carboplatin regimen were mainly delivered as AC in 71.2% and 21.7% of pts. In NC, all pts received methotrexate-vinblastine-doxorubicin-cisplatin (MVAC) or dose-dense MVAC. Median number of cycles was 4 in each group. After NC, RC has been realized in 173 (90%) and 51 pts (82%) in NC and cN+, respectively. In 17 unoperated pts, concomitant chemoradiotherapy was performed. Median follow-up was 24.6 months. Respectively, 133 (59%), 61 (32%), and 22 (35%) pts have relapsed in AC, NC, and cN+; 74%, 63%, and 71% of them received chemotherapy for metastasis. Also 133 (59%), 41 (21%), and 18 (29%) pts died, mostly (90%) due to recurrence. Three-year OS and CRS rates were 54%, 68%, and 56% (p=0.02), and 37%, 53%, and 49% (p=0.038) in AC, NC, and cN+, respectively. In multivariate analysis, only AC (HR: 1.64, 95% CI 1.18-2.30, p=0.001) remained significantly associated with shortened OS. Conclusions: In this large retrospective study reporting real-life survivals, 3-year OS was longer in pts receiving NC, both in cN0 and in cN+ groups, than in pts treated with AC. Although several selection bias can be emphasized preventing us from drawing definitive conclusions, AC appeared to be associated with a poorer prognosis.
A randomized study of gemcitabine/cisplatin versus single-agent gemcitabine in patients with biliary tract cancer
Authors: J. Furuse, T. Okusaka, M. Miyazaki, H. Taniai, Y. Nimura
Journal: Journal of Clinical Oncology (2009)

4579 Background: Biliary tract cancers (BTC) are not common but increasing in the US and Europe, and more prevalent in South America and Asia including Japan. Gemcitabine (G) and cisplatin (C) are now deemed as key drugs based on the accumulated literature. This is the first study to compare GC combination with G alone in Japan, even though one phase 3 trial (ABC-02) is ongoing in UK. Methods: 84 Japanese pts, aged ≥ 20 years, with histologically or cytologically confirmed advanced BTC, Performance Status 0 - 1, with adequate bone-marrow, hepatic and renal function were randomized. 83 pts received either C 25 mg/m2 plus G 1000 mg/m2 on days 1, and 8 of each 21-day cycle (GC-arm) or G 1000 mg/m2 on days 1, 8 and 15 of each 28-day cycle (G-arm). Treatments were repeated up to a maximum of 16 cycles of GC or 12 of G until disease progression or unacceptable toxicity occurred. Tumor response was evaluated using RECIST criteria by an independent review committee. The primary end-point of the study was 1- year survival rate. Safety, response rate, duration of progression-free survival were also evaluated. Results: A total of 83 pts (19 extrahepatic bile duct cancer, 28 intrahepatic bile duct cancer, 32 gallbladder cancer and 4 ampullary carcinoma) were eligible for the study protocol defined analysis set (Full Analysis Set, FAS); GC-arm n=41 and G-arm n=42. Baseline characteristics were similar between the two arms: median ages were 65.0 vs 66.5, females were 56.1 vs 50.0%. All pts completed at least one cycle of therapy, yielding a total of 247 cycles (median 6) in GC vs 203 (median 4) in G. The overall response rates were 19.5% (95% CI: 8.8, 34.9) vs 11.9 (95% CI: 4.0, 25.6). The results on survival will be determined and presented at the meeting. The most commonly reported grade 3 or 4 toxicities were: neutropenia (56.1 vs 38.1%), thrombocytopenia (39.0 vs 7.1%), leukopenia (29.3 vs 19.0%), hemoglobin decrease (36.6 vs 16.7%) and γ-GTP increase (29.3 vs 35.7%). Grade 3 acute renal failure was reported in 1 pt on GC. Conclusions: The combination therapy of GC would be an effective and well-tolerated chemotherapy regimen for Japanese pts with advanced BTC. [Table: see text]