tbuckley/cabot-search huggingface dataset:
A phase II study of cisplatin (P) plus etoposide (E) plus bevacizumab (B) for previously untreated extensive stage small cell lung cancer (SCLC) (E3501): A trial of the Eastern Cooperative Oncology Group
Authors: A. Sandler, S. Szwaric, A. Dowlati, D. F. Moore, J. H. Schiller
Journal: Journal of Clinical Oncology (2007)

7564 Background: Scientific evidence supports the concept that the growth of solid tumors, including SCLC, is dependent on angiogenesis. Bevacizumab, a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), has been shown to improve survival when combined with chemotherapy in non-small cell lung cancer. PE is a standard regimen for use in SCLC. Thus, we proposed this study of PE plus B in patients (pts) with previously untreated extensive stage SCLC. Methods: Pts with previously untreated extensive SCLC with a performance status 0–2, received P (60 mg/m 2) IV followed by E (120 mg/ m 2) IV followed by B (15 mg/kg) IV infusion on day 1, with E repeated on days 2 and 3 of a 21-day cycle for 4 cycles or until progressive disease (PD). Pts not experiencing PD continued bevacizumab until disease progression or unacceptable toxicity. The primary endpoint was per cent of patients alive at 6 months. Results: From 6/8/04 to 8/18/06 (includes a ten month accrual suspension to evaluate data), 64 eligible pts were accrued. Patient characteristics: median age of 65.5 years (range: 45–83), 44% males, 95% Caucasian and 9% were performance status = 2. A median of 6 cycles of treatment were administered (range: 1–12). There is toxicity data on 58 pts. The most common treatment-related grade 3 &amp; 4 toxicities were: neutropenia (7 &amp; 26 pts), thrombocytopenia (8 &amp; 2 pts), fatigue (10 pts, grade 3 only), hypertension (4 pts, grade 3 only), febrile neutropenia (2 pts) and dehydration (3 pts, grade 3 only). Two pts experienced grade 5 toxicities (hypotension and infection with grade ¾ neutropenia). There were no grade ≥3 hemorrhagic events. Response information is available on 39 pts. There have been 4 complete responses and 23 partial responses for an overall response rate of 69% (90% exact CI: (55%, 81%). The proportion of pts alive and progression- free at 6 months was 33% (95% CI: 17%, 49%). Conclusions: Preliminary results indicate that the addition of B to the combination of PE in patients with previously untreated extensive stage SCLC appears promising. A randomized phase III trial comparing PE to PE + B is under consideration. No significant financial relationships to disclose.
Mutational analysis of plasma DNA from patients (pts) in the phase III GRID study of regorafenib (REG) versus placebo (PL) in tyrosine kinase inhibitor (TKI)-refractory GIST: Correlating genotype with clinical outcomes.
Authors: George D. Demetri, Michael Jeffers, Peter Reichardt, Yoon-Koo Kang, Jean-Yves Blay, Piotr Rutkowski, Hans Gelderblom, Peter Hohenberger, Michael Gordon Leahy, Margaret von Mehren, Heikki Joensuu, Giuseppe Badalamenti, Martin E. Blackstein, Axel Le Cesne, Patrick Schoffski, Robert G. Maki, Jian-Ming Xu, Toshirou Nishida, Iris Kuss, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2013)

10503 Background: The phase III GRID study showed that REG provides a significant improvement in progression-free survival (PFS) compared with PL in pts with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib (IM) and sunitinib (SU; HR 0.27, p&lt;0.0001). Determining GIST genotype in TKI-refractory disease has proven challenging due to inter-tumoral heterogeneity and pt preference to avoid serial biopsies. To overcome this, we analysed circulating DNA in plasma as a source of tumor DNA and studied the correlation between mutational status and clinical outcome. Methods: DNA was isolated from both archival tumor tissue (n=102) and plasma at baseline (n=163) and analyzed for mutations via Sanger sequencing (tissue) or BEAMing (plasma). Results: Mutational frequencies for tumor tissue samples were: KIT, 66%; PDGFRA, 3%; KRAS, 1%; BRAF, 0%. For plasma, frequencies were: KIT, 58%; PDGFRA, 1%; KRAS, 1 out of 2 samples, BRAF, 0%. Detection of primary KIT mutations showed 84% concordance between tissue and plasma. Secondary KIT mutations were more commonly detected in plasma (47%) than in tissue (12%). Subgroup analysis based on mutational status showed an improved PFS in REG-treated pts vs PL in all subgroups by both central and local review of imaging studies. The presence of a secondary KIT mutation in plasma was associated with shorter PFS in pts receiving PL (HR 1.82, p=0.05). Pts with a KIT-exon 9 mutation received IM for a shorter period of time, and SU for a longer period of time, relative to other GIST genotypes. Pts with a PDGFRA mutation showed variable clinical responses, while 1/1 KRAS-mutant GIST did not respond well to IM, SU, or REG. Conclusions: KIT mutational status correlated to IM and SU treatment duration. While consistent with prior reports using tissue sampling, this validates the utility of plasma-based circulating DNA analysis of target oncogenes. Secondary KIT mutations appear to have a negative prognostic impact in GIST, while the clinical benefit of REG vs PL was not influenced by KIT mutational status. Clinical trial information: NCT01271712.
Extended duration temozolomide in patients with glioblastoma multiforme.
Authors: M. W. Pitz, M. E. Lipson, B. Hosseini, K. Guilbert, D. Lister, C. L. Mihalcioiu, D. D. Eisenstat
Journal: Journal of Clinical Oncology (2010)

e12538 Background: Standard treatment for glioblastoma multiforme (GBM) includes surgical resection, temozolomide (TMZ) with radiotherapy, and adjuvant TMZ. Phase III data has shown that patients treated with 6 months of adjuvant TMZ had a median overall survival (OS) of 14.6 months with a 26.9% PFS and 61.1% OS at 1 year. The optimal duration of adjuvant therapy and whether additional agents may improve outcome is a matter of intense study. Methods: From 2002 to 2009, consecutive patients from a regional cancer center were assessed. To be eligible, patients required histological confirmation of GBM, a good performance status, and must have received concurrent radiation and TMZ. Each patient went on to receive up to 30 cycles of TMZ (150-200 mg/m2) concurrent with cis-retinoic acid (CRA) (50 mg/m2 BID). Treatment was stopped or changed if there was intolerance to therapy or clinical/radiologic evidence of progression. TMZ was continued if patients were intolerant only to the side effects of CRA. Results: Of the 79 patients that were included, mean age was 57 and 63.3% were male. The mean number of cycles of TMZ given was 8.5, with 2 patients receiving 30 cycles and 7 receiving 24 cycles. 18 patients (22.7%) received at least 12 cycles of TMZ. The mean number of TMZ cycles given concurrently with CRA was 6.7, with 15 patients (19%) receiving at least 12 concurrent cycles. No patients discontinued TMZ due to intolerance. Median OS was 17.1 months, and median progression-free survival (PFS) on TMZ was 9.6 months. The 12 month PFS was 36.7% and OS was 70.9%. Multivariable analysis determined that the extent of surgery (biopsy: HR 4.1, p = 0.003; partial resection: HR 2.3, p = 0.027) and age (HR 1.03, p = 0.006) were independently associated with survival. Survival did not improve over time. Conclusions: Extended duration TMZ is a well- tolerated treatment for up to 30 cycles. Patients treated in this manner had favorable survival compared to standard therapy. The combination of TMZ and CRA given monthly until progression or intolerance should be studied in a prospective randomized trial in the adjuvant setting. No significant financial relationships to disclose.
Sexual dysfunction in patients with cancer
Authors: C. M. Bonini Colmano, S. Molnar, L. M. Salvano, G. Molina Barrios, M. Arevalo, P. Di Marco, M. L. Rizzi, C. Dubersarsky, M. Lavarda, G. D. Jarchum
Journal: Journal of Clinical Oncology (2007)

19653 Background: Malignant diseases have a strong influence in quality of life, being sexuality one of the most affected variables. The objetive is to determine the prevalence of sexual dysfunction in a cohort of patients with cancer and its relationship with the following: pain, fatigue, nausea, vomiting, mechanisms of adaptation to stress, anxiety and depression. Methods: Anonymous questionnaires were used, including: treatment, adverse events, Zimong and Snaith depression and anxiety scale, sexual dysfunction questionnaire, coping strategies of Tobin David, Hopwood body image scale and the analogical visual test for pain evaluation. Results: Between January and August 2006, sixty four patients were evaluated; 72% were women; median age: 50 years old. Libido was absent in 50%; this was associated with gender (better in men; p=0,05) and the presence of pain (p=0,05) and fatigue (p=0,05) but not with age. All patients who had intact libido also had arousal and orgasms; this was more prevalent in men than in women and in subjects younger than 60 years. Arousal was absent in 47% of cases. Forty four percent of men had erectile dysfunction; this was present in all patients older than 60 years. Frequency of intercourses was decreased in 75%. Fifty eight percent of patients said that their sexuality was better before the diagnosis of their disease. Interestingly, 85% didn’t talk to their doctors about their sexual problems. Conclusions: One out of 2 patients had sexual dysfunction, predominantly women. Sexuality was affected mainly by pain and fatigue. Although normal libido was present in all ages, subjects older than 60 years had less arousal and orgasms. No significant financial relationships to disclose.
Testosterone levels in men undergoing treatment for malignant gliomas.
Authors: M. Holdhoff, X. Ye, L. Blair, S. A. Grossman, J. O. Blakeley
Journal: Journal of Clinical Oncology (2010)

2017 Background: Patients with malignant gliomas (MG) are exposed to intensive treatments including surgery, radiation, chemotherapy and glucocorticoids. Low serum testosterone (T) has been reported in men with systemic cancers, but little is known about this phenomenon in patients with MG. MG patients often develop symptoms of fatigue and muscle weakness. We hypothesized that these symptoms could be related to low T and conducted a retrospective study to assess serum T in men with MG. Methods: A total of 216 male patients with MG seen in the Brain Cancer Program outpatient clinic between January 2008 and December 2009 were screened for serum T levels. 44 patients were identified as having serum T evaluated. Hypogonadal levels were defined as < 262 ng/dL for men 20-49 yrs (normal range 262-1593 ng/dL) and < 181 ng/dL for men ≥ 50 yrs (normal range 181-758 ng/dL). Age and dexamethasone (dex) dose (< 4 mg/d, low dose or ≥ 4 mg/d, high dose) were recorded. Results: Of the 44 men who had serum T assessed, 34 (77.3%, 95% CI: 62-89%) had age-adjusted T levels consistent with hypogonadism. The median T level of all patients was 109 ng/dL (range, 19-580 ng/dL). Men <49 had a median T of 177 ng/dL (n = 14, range 19-558 ng/dL) and men > 50 had a median T of 92 ng/dL (n = 30, range 19-580 ng/dL). The median T level for patients on low-dose dex (251 ng/dL; n = 15; range, 25-580 ng/dL) was significantly higher than for patients on high-dose dex (85 ng/dL; n = 29; range 19-269 ng/dL; p = 0.0001). Age-adjusted hypogonadism occurred at both high (27 of 29 patients; 93.1%) and low (7 of 15 patients; 46.7%) dex doses. Conclusions: Men treated with standard therapy for MG with symptoms of fatigue and weakness frequently had serum T consistent with hypogonadism (77.3%). T levels were lower than age- based norms and significantly lower in patients on high- versus low-dose dex. Hypogonadism may be common in men treated for MG and is potentially reversible. Further investigation is needed to define its contribution to quality of life in men with MG and to identify possible treatments. This research was supported by a grant from the Lance Armstrong Foundation. No significant financial relationships to disclose.
Review of<i>Side Effects</i>, DVD All Regions, 90 minutes, Hummingbird Pictures, USA, 2006; and<i>Money Talks: Profits Before Patient Safety</i>, DVD Region 1, 50 minutes, Hummingbird Pictures, USA, 2006.
Authors: Jessica Berg
Journal: The American Journal of Bioethics (2007)

"Review of Side Effects, DVD All Regions, 90 minutes, Hummingbird Pictures, USA, 2006; and Money Talks: Profits Before Patient Safety, DVD Region 1, 50 minutes, Hummingbird Pictures, USA, 2006.." , 7(3), p. 58 This is the inaugural column for movie reviews. We encourage the submission of movies and movie reviews relevant to bioethics. In particular, we are interested in films—documentaries, independent film, or mainstream Hollywood entertainment—that can be used in teaching bioethics. For specific guidelines on submitting movie reviews, see our website www.bioethics.net
The importance of an isolated central nervous system relapse in children with acute lymphoblastic leukemia.
Authors: S L George, J J Ochs, A M Mauer, J V Simone
Journal: Journal of Clinical Oncology (1985)

We assessed the influence of an initial isolated meningeal relapse on treatment outcome in 839 children with acute lymphoblastic leukemia (ALL) who were admitted to St Jude Children's Research Hospital (Memphis) from mid-1967 through mid-1979. The patients were entered in a series of five clinical trials (Total Therapy Studies V through IX), each designed to test one or more modifications of treatment for ALL. Two groups were compared: 699 children who received CNS prophylaxis (2,400-rad craniospinal irradiation or 2,400-rad cranial irradiation plus intrathecal methotrexate) v 56 who did not. Our results, obtained with a time-dependent covariate model and a matching technique, indicate a 2 to 3.5-fold increase in the risk of hematologic relapse or death among patients who experienced an isolated CNS relapse compared with similar patients (matched for leukocyte count and length of complete remission) who remained free of CNS involvement. Of the 107 children with an initial isolated CNS relapse, 89 (83%) have died or have had a subsequent relapse. There was no detectable difference in the rate of hematologic relapse or death after a CNS relapse between patients who had received preventive therapy and those who had not. We conclude that CNS prophylaxis is important both for the prevention of initial CNS leukemia and for reducing the risk of hematologic relapse or death subsequent to a CNS relapse.
Weekly docetaxel (D) versus daily low dose cisplatin (P)/ fluorouracil (F) as neoadjuvant chemoradiotherapy (CRT) in patients with advanced esophageal cancer: Nonrandomized phase II results of a single institute
Authors: Y. Kajiyama, M. Okumura, F. Isayama, Y. Iwanuma, N. Tomita, T. Amano, K. Karasawa, H. Hirokawa, M. Tsurumaru
Journal: Journal of Clinical Oncology (2005)

4259 Background: (D) is now introduced as an agent for chemoradiotherapy in patients with head and neck cancer. We began to use (D) consecutively in patients with advanced esophageal cancer from January 2004 as an agent for neoadjuvant CRT, when the tumor was suspicious for invading to adjacent organs. We compared both pathologic effects and adverse events between (D) and (P) + (F) CRT as a neoadjuvant treatment. Methods: The neoadjuvant regimen was 40Gys of radiation with weekly (D: 10mg/m2) or daily (P: 10mg/body) + (F: 500mg/body). During CRT, adverse events were recorded according to NCI-CTC (ver.2.0). A month following CRT, transthoracic esophagectomy with lymph nodes dissection was performed, and pathologic effects of neoadjuvant CRT were judged. We consider a case as a pathologic responder when viable cancer cells account for less than 1/3 of tumor tissue microscopically. Results: 11 pts received (D) CRT, and 28 pts received (P) + (F) CRT. Pathologic response rate was 73% in (D), and 66% in (P) + (F) (p=0.245). The rates of adverse events of blood/bone marrow were significantly lower in (D) than (P) + (F). The frequency of grade 3 adverse events in (D) vs. (P) + (F) was 9% vs. 32% (WBC: p=0.007), 0% vs. 14% (Hemoglobin: p=0.024), 0% vs. 11% (Platelets: p=0.025). The rates of other grade 3 events in such as hepatic, renal or gastrointestinal category were rare and no significant difference was observed. Conclusions: (D) CRT is as efficacious as (P) + (F) CRT, and showed significantly fewer blood/bone marrow adverse events. (D) CRT is a promising and safe regimen for esophageal cancer treatment. No significant financial relationships to disclose.
Basic science and translational research
Authors: D Power, J Przybylo, M Capanu, V Devlin, J Vijai, T Kirchhoff, L Saltz, K Offit, Z Stadler, L Mekenkamp, J Haan, M Koopman, S Teerenstra, L Mol, B Ylstra, G Meijer, C Punt, I Nagtegaal, J Cheadle, C Smith, D Fisher, T Maughan, V Moskvina, A Meade, H West, R Kaplan, C Lo Nigro, N Syed, L Lattanzio, A Dasoula, M Monteverde, E Hatzimichael, A Papoudou-Bai, P Schmid, M Merlano, T Crook, L Costa, I Alho, A Fernandes, S Casimiro, I Fernandes, E Gangolli, M Motwani, Y Wang, B Lee, V Modur, H Linardou, K Kalogeras, R Wirtz, E Briasoulis, H Gogas, D Pectasides, H Kalofonos, D Bafaloukos, D Skarlos, G Fountzilas
Journal: Annals of Oncology (2010)
Randomized Phase III Trial Comparing the New Potent and Selective Third-Generation Aromatase Inhibitor Vorozole With Megestrol Acetate in Postmenopausal Advanced Breast Cancer Patients
Authors: P. E. Goss, E. P. Winer, I. F. Tannock, L. H. Schwartz on behalf of the North American Vorozole Study Grou
Journal: Journal of Clinical Oncology (1999)

To compare the efficacy and safety of vorozole (VOR) 2.5 mg once daily with that of megestrol acetate (MA) 40 mg four times per day as second-line therapy in postmenopausal women with advanced breast cancer whose disease progressed after tamoxifen treatment.A total of 452 patients were enrolled onto an open, multicenter, randomized phase III trial comparing VOR to MA for tumor response, safety, and quality of life (as indicated by the Functional Living Index-Cancer score).Vorozole produced a response rate of 9.7%, compared with 6.8% for MA (P = .24). Clinical benefit (complete response + partial response + no change in > 6 months) was demonstrated in 23.5% and 27.2% of patients treated with VOR and MA, respectively (P = .42). Median duration of response was 18.2 months for VOR versus 12.5 months for MA (P = .074). There was no significant difference in time to progression or survival between the treatment groups. Discontinuation of treatment because of adverse events occurred less frequently in the VOR-treated group (3.1% v 6.2%; P = .18). Patients on the VOR arm reported significantly more nausea, hot flushes, arthralgia, upper respiratory tract infection, anorexia, and paresthesia, whereas those treated with MA had significantly more dyspnea, increased appetite, and weight increase. There was no difference between the two treatment groups in Functional Living Index-Cancer scores (total or subscales). However, when analyzed by objective response, patients with complete or partial responses (P = .032) or no change (P = .033) who were receiving VOR had significant improvement in the psychologic well-being subscale, compared with patients given MA.Vorozole is well tolerated and as effective as MA in the treatment of postmenopausal advanced breast cancer patients with disease progression after tamoxifen treatment.
Sociodemographic factors influencing Breslow thickness at diagnosis for patients with melanoma
Authors: K. B. Stitzenberg, N. E. Thomas, M. Berwick, H. Anton-Culver, U. J. Mujumdar, R. C. Millikan
Journal: Journal of Clinical Oncology (2007)

6552 Background: In previous work, we demonstrated that Breslow thickness at diagnosis is significantly related to distance to provider for patients with melanoma in North Carolina (NC). Expanding the study population to include patients in New Jersey (NJ) and southern California (CA), we hypothesize that distance to provider is an effective measure of access to melanoma care regardless of geographic region. Methods: An IRB-approved secondary data analysis was performed of all incident cases of invasive cutaneous melanoma in 2000 from 3 population-based ascertainment areas (CA, NC, NJ). Patients and providers were geocoded to street address; Euclidian distances between patients and providers were calculated. The outcome variable, Breslow thickness at diagnosis, was logged for analysis. Simple and multiple linear regression were used to test associations between Breslow thickness and multiple sociodemographic factors. Results: Of 1,408 eligible cases, 16% were excluded for missing Breslow data. Median Breslow thickness was 0.6 mm (range 0.01–30.0 mm). Median distance to provider was 7 miles (range 0–372 miles). There was no significant difference in Breslow between the 3 geographic regions. Males had on average 15.5% thicker tumors than females, p=0.009. Patients 51–80 years old had 15.3% thicker tumors than patients =50, p=0.015, and those &gt;80 had 64.3% thicker tumors than patients =50, p&lt;0.001. For all patients, Breslow thickness increased only 2% for each 10 mile increase in distance, p=0.047. However, when limited to patients from rural areas, each 10 mile increase in distance corresponded to an 8% increase in Breslow, p&lt;0.001. Meanwhile, Breslow was not associated with any area-based measures of rurality or provider supply. Each 1% increase in poverty rate corresponded to a 1% increase in Breslow, p=0.036. Conclusion: Breslow thickness at diagnosis is strongly correlated with distance to provider, especially for patients from rural areas. Distance to provider is a better measure of access to melanoma care than area-based measures of rurality. No significant financial relationships to disclose.