tbuckley/cabot-search huggingface dataset:
18FDG-PET in NSCLC: Relationship between histology and EGFR mutation with metabolic activity.
Authors: C. D. Rolfo, M. Valero, A. Arrivi
Journal: Journal of Clinical Oncology (2010)

e18128 Background: 18FDG-PET is a diagnostic and monitoring tool widely used in patients with NSCLC. The uptake value (SUVmax) has been as a prognostic factor in these patients. We analyzed the relationship among histology type, EGFR mutation and tumor metabolic activity in patients with NSCLC. Methods: We retrospective analyzed 113 patients with NSCLC diagnosed at our institution. All patients had a 18 FDG-PET before any treatment. Patients were classifiedaccording to histology as NSCLC (adenocarcinoma, squamous, large cell and unclassified NSCLC). The analysis of the 18 FDG-PET images was performed both qualitatively and quantitatively (calculating the SUVmax in the different sites of disease). In a subgroup of patients with non-squamous lung carcinoma EGFR mutation determination was preformed. Results: 113 patients with NSCLC were analyzed: 62.8% had BAC (and adenocarcinoma, squamous 8%, 15% large cell undifferentiated and 14.2% unclassified NSCLC. The median SUVmax in lung was 8.21 (standard deviation 4.41) in adenocarcinoma, 13.07 (5.75) in squamous, 8.57 (4.23) in large-cell/undifferentiated, 9.12 (6.02) NSCLC unclassified. ANOVA analysis between histology and metabolic activity in the lung localitation and bone metastasis showed statistically significant differences (p < 0.05) for every histological subgroup. No statistically significant relationship was found between the 18FDG uptake in other locations. In 55 of 113 patients with NSCLC, EGFR mutation was determined and 16.4% had the mutation. We found no statistically significant differences in SUVmax between mutated and non-mutated patients. Conclusions: Our study points a relationship between tumor histology and metabolic activity in the lung. EGFR mutation does not seem to have a direct relationship with the degree of 18FDG lung uptake in opposite to Asian reports. Further studies are necessary to corroborate our findings. No significant financial relationships to disclose.
Aging and the kidney.
Authors: M Epstein
Journal: Journal of the American Society of Nephrology (1996)

A host of abnormalities of renal structure and function accompanies advancing age. An appreciation of methodologic considerations, including population selection, that might confound the assessment of the effects of aging on renal function has prompted a recent reappraisal. Earlier studies assessed the effects of aging by utilizing cross-sectional studies and institutionalized elderly subjects, with their attendant drawbacks. Recent longitudinal studies have utilized appropriate patient cohorts, selected for lock of renal disease, including potential kidney transplant donors. These studies indicate that the morphological and functional changes of aging tend to be less marked than previously thought. The common denominator of these functional changes is a diminution in renal reserve, along with constraints on the kidney's ability to respond appropriately to challenges of either excesses or deficits. Although these alterations are unlikely to be of major clinical consequence under everyday conditions, they attain clinical significance when residual renal function is challenged by the superimposition of an acute illness. Finally, it should be emphasized that elderly patients frequently suffer from comorbid conditions, such as hypertension and heart disease, that may be additive to the changes of aging, thereby amplifying these abnormalities.
Nandrolone decanoate treatment in anemia of patients with cancer: Phase II clinical study.
Authors: B. Chewaskulyong, S. Thongprasert, B. Chawla, D. Mehta, M. S. Chawla
Journal: Journal of Clinical Oncology (2011)

e19581 Background: Anemia is an important clinical problem in cancer patients. Nandrolone decanoate is an anabolic steroid that has been used to treat anemia in renal failure. It is considered one of the least virilizing preparations. We perform a study to evaluate the efficacy, safety and tolerability of nandrolone decanoate. Methods: Cancer patients(pts) with Hemoglobin (Hb) level < 10 g/dL, age ≥18 and ≤ 65 years,perfomance status (PS) 0-2, adequate hepatic functions,normal serum calcium and prothrombin time, life expectancy of at least 12 weeks, recovery from all acute toxicities of prior therapies were eligible. Weekly nandrolone decanoate was given intramuscularly 200 mg in male and 100 mg in female pts for 12 weeks. Target Hb was 12 g/dL.The research was approved by local ethics committee and funding by Thorek memorial foundation. Results: Twenty five out of thirty enrolled pts who were receving chemotherapy from 16 May 2008 to 4 October 2010 were eligible: 8 males,17 females,median age was 58 years (range 33-65),with 13 had lung cancer, 5 had cholangiocarcinoma and 1each patient for bladder, breast,stomach, rectum,colon, small cell cancer of orbit, giant cell tumor with lung metastasis. Reasons for 5 ineligible pts were increased liver enzyme (1), high fasting blood glucose (2), pneumonia (1), and history of erythropoietin usage(1). Twelve pts(48%) were responders (Hb increase ≥ 1 g/dL), by 24% respond within 4 weeks and 24% respond within 8 weeks. However the mean Hb at baseline, 4wk, 8wk and 12 wk were 9.1±0.6, 9.2±0.8, 9.5±1.1 and 9.9±1.7 g/dL respectively, which do not different significantly (p=.06) by repeated ANOVA test. Four pts (12%) did not comple the study because need blood transfusion. The common adverse events were smooth ski n (92%) weight gain (84%),mild erythema of face (64%), increased appetite (52%), mood swing (40%), edema (32%) and hoarseness (28%), fatigue (24%), myalgia/arthralgia (24%), increased LDL-cholesterol (20%), increased fasting blood glucose (16%), increased serum creatinine (16%), and penile erection(12%). Conclusions: Nandrolone decanoate appears to be feasible and safe allowing treatment of anemia in cancer pts. It may be an alternative choice of treatment of anemia in the future.
The taxane-enhancer STA-4783 induces Hsp70 expression and apoptosis via an oxidative stress mechanism
Authors: J. Kirshner, Z. Du, J. Kepros, V. Balasubramanyam, S. He, M. Zhang, C. Yang, J. Barsoum, J. Bertin
Journal: Journal of Clinical Oncology (2007)

14107 Background: STA-4783 is an inducer of Hsp70 expression and apoptosis that recently completed a successful Phase II clinical trial in melanoma. In a double-blind, randomized, controlled trial in patients with Stage IV disease, STA-4783 plus paclitaxel doubled progression-free survival compared to paclitaxel alone (Perspectives in Melanoma X and the Third International Melanoma Research Congress, 2006). The mechanism by which STA-4783 synergizes with paclitaxel is not fully understood. To identify the major pathway modulated by STA- 4783 in vitro, a transcriptional profiling analysis of drug-treated melanoma cells was performed. Methods: Transcriptional profiling was performed on Hs294T and MDA-MB-435 melanoma cell lines treated with STA-4783. The induction of Hsp70 RNA and other human genes was monitored by Real Time-PCR (RT-PCR) analysis. Measurement of reactive oxygen species (ROS) was performed in human cells using the Carboxy-H 2 DCFDA probe. Levels of apoptotic cell death were determined by flow cytometry analysis using an Annexin V specific probe. Results: Transcriptional profiling revealed that STA-4783 induced the expression of numerous gene families known to be regulated by oxidative stress, including heat shock proteins and metallothioneins. STA-4783 induced the generation of ROS in cells resulting in the oxidation and activation of the Carboxy-H 2 DCFDA fluorescent probe. The antioxidants N-Acetyl Cysteine (NAC) and Tiron potently blocked the induction of Hsp70 RNA and apoptotic cell death. Conclusions: STA-4783 induces oxidative stress in cells resulting in Hsp70 induction and apoptotic cell death. Although STA-4783 initially induced a transient protective response, apoptotic cell death occurred due to sustained oxidative stress. Cancer cells produce more ROS than normal cells and are thus more sensitive to insults that induce oxidative stress. The induction of ROS in melanoma cells by STA-4783 may therefore enhance the efficacy of paclitaxel in vivo. STA-4783 belongs to a novel class of anticancer agents that induce cell death by pushing the cancer cell beyond its oxidative stress breaking point. [Table: see text]
A randomized trial of levamisole versus placebo as adjuvant therapy in malignant melanoma.
Authors: L E Spitler
Journal: Journal of Clinical Oncology (1991)

We conducted a long-term follow-up (median, 10.5 years) of patients included in a randomized trial of levamisole versus placebo as surgical adjuvant therapy in 203 patients with malignant melanoma. Of the patients randomized, 104 received levamisole, and 99 received placebo. The results show that there is no difference between the treatment and control groups with regard to any of the three end points analyzed. These included disease-free interval, time to appearance of visceral metastasis, and survival. Moreover, there was no significant difference between the treatment and control groups after adjusting for age, sex, or stage of disease.
Rehospitalization rates for patients with pneumonia who require supplemental oxygen therapy following hospital discharge
Authors: Brian Carlin, Kim Wiles, Dan Easley
Journal: European Respiratory Journal (2012)

Objective: To compare the hospital readmission rates for patients with pneumonia who require supplemental oxygen therapy following an exacerbation who are entered into a home-care based, respiratory therapist centered transition of care program.

Method: Patients with a diagnosis of pneumonia who required supplemental oxygen therapy on hospital discharge were entered into a post hospitalization transition of care program {Discharge, Assessment and Summary @ Home (D.A.S.H., Klingensmith HealthCare, Ford City, PA)]. Patients with a diagnosis of COPD were excluded from this analysis. The program consists of face to face visits by a respiratory therapist with the patient on days 2, 7, and 30 following hospital discharge. Education, behavior modification, skills training, oxygen titration during performance of activities of daily living, clinical assessment, and adherence data collection are components of the program. The 30 day readmission rates following discharge for those patients entered into the program over a twenty four month period were evaluated.

Results: 22 consecutive patients with pneumonia from 23 different hospitals were enrolled into the program over the two year period. None (0%) of the patients were rehospitalized within the first thirty days following hospital discharge.

Conclusions: The use of a multiple visit respiratory therapist based patient centered management program resulted in a significant decrease in the 30 day readmission rates for those patients who were discharged following a hospitalization for pneumonia.
Effect of adjuvant immunochemotherapy with PSK for colon cancer patients showing oncogenic β-catenin activation in primary tumor
Authors: K. Yamashita, H. Nakazato, K. Ito, A. Ougolkov, Y. Takahashi, M. Mai, T. Minamoto
Journal: Journal of Clinical Oncology (2004)

3650 Background & Aim: β-catenin translocated into cell nucleus functions as an oncogene transactivating a number of oncogenes. Here, we conducted a large-scale analysis of β-catenin activation in human colon cancer to determine potential clinical importance of this oncoprotein, and to identify patients, enrolled in a randomized controlled trial (CIP Study), who have a benefit from adjuvant immunochemotherapy (5-Fu 200mg/day; p.o. + PSK 3000mg/day; p.o.) or chemotherapy (5-Fu 200mg/day; p.o.) alone after curative resection of the cancer. Methods: Subjecting 202 colon cancer patients, we determined the patterns of β-catenin activation in primary tumors and correlated data with survival of patients undergoing different protocols of adjuvant therapies. Results: In 53% of patients, we found two distinct patterns of β-catenin activation on the basis of its nuclear accumulation (NA) in tumor cells: diffuse NA (NAd) in 89 cases (44%) and selective NA at tumor invasion front (NAinv) in 18 (9%). While NAinv pattern was significantly correlated with advanced Dukes' stage, resulting in extremely unfavorable clinical outcome, no significant difference in survival was observed between the two groups of the patients underwent different therapy protocols. In patients with NAd pattern of β-catenin activation, immunochemotherapy significantly improved 5-year cancer death- (5yCDS) and over all (5yOAS) survival rates in comparison with those with chemotherapy alone (n=55) (Table). Multivariate analysis determined Dukes' tumor stage and administrating PSK as independent prognosis factors in these patients. Conclusion: Our results indicates that of different patterns of β-catenin activation that determine malignant potential of tumors, the presence of NAd pattern could identify patients with colon cancer better responding to the immunotherapy with PSK. No significant financial relationships to disclose.
Pentostatin and cyclophosphamide compared to pentostatin, cyclophosphamide, and rituximab as salvage therapy for patients with chronic lymphocytic leukemia
Authors: M. A. Weiss, N. Lamanna, M. Kalaycio, J. Jurcic, P. Maslak, A. Gencarelli, D. Scheinberg, D. Horgan
Journal: Journal of Clinical Oncology (2004)

6568 Background: Combination therapy with purine analogs, alkylators, and/or monoclonal antibodies represents a promising new approach to treatment of patients with chronic lymphocytic leukemia (CLL). Most regimens have utilized fludarabine as the purine analog but the severe myelosuppression and immunosuppression of these combinations requires careful attention to dosing and schedule to minimize these toxic complications. Of the purine analogs active in CLL, pentostatin appears to be least myelosuppressive. Methods: We have treated sequential cohorts of patients first with pentostatin and cyclophosphamide (PC regimen) and more recently with the 3 drug combination pentostatin, cyclophosphamide, and rituximab (PCR regimen). We now report on 45 patients with CLL treated with these regimens. The PC regimen (21 patients) consists of pentostatin 4mg/m2 and cyclophosphamide 600mg/m2 administered on the same day every 3 weeks for 6 treatments. The PCR regimen (24 patients) is identical to PC but with rituximab 375mg/m2 added to cycles 2–6. Supportive care included hydration (and monitoring renal function), anti-emetics, prophylactic filgrastim, sulfamethoxazole/trimethoprim, and acyclovir. Results: For patients treated with PC and PCR respectively, the median number of prior treatments were 3 (range 1–5) and 2 (range 1–7), and the median ages were 63 (range 32–77) and 62 (range 44–80). Responses to PC were seen in 81% with CR in 19% compared to the PCR regimen with responses in 80% and CRs in 20%. In both cohorts even fludarabine refractory patients typically responded to therapy (77% treated with PC and 88% treated with PCR). Grade 3 or 4 toxicity in the two regimens (PC compared to PCR) was comparable including neutropenia (33% vs 43%), thrombocytopenia (33% vs 10%), and infection (9% vs 19%). Conclusions: These data indicate that both regimens are highly active and well tolerated in this patient population and that the addition of rituximab does not appear to substantially increase the toxicity. We plan to further study this regimen in patients with untreated CLL. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration SuperGen
Lung neuroendocrine tumor (NET) patient (pt)-reported experience: Results from the first global NET pt surveyA collaboration between the international neuroendocrine cancer alliance (INCA) and Novartis pharmaceuticals.
Authors: Dan Granberg, Maia Sissons, Teodora Kolarova, Grace Goldstein, John Leyden
Journal: Journal of Clinical Oncology (2015)

e17739 Background: Lung NETs are rare and often asymptomatic; diagnosis may thus be substantially delayed, impacting survival. We present global data on pts' experiences with lung NETs. Methods: In 2014 (Feb-May), 1928 NET pts from > 12 countries (Americas, Asia, Europe, Oceania) participated in a survey, conducted by Hall & Partners on behalf of INCA/Novartis and funded by Novartis, on the NET pt experience (comparisons significant at P< 0.05). Results: 12% of pts had lung NETs, primarily nonfunctional/asymptomatic (56% of pts who knew the status, n = 160) and low grade (G1; 55%, n = 140). 61% were diagnosed < 5 years ago and had not visited (63%)/been diagnosed (88%) at a NET specialist center. 50% required ≥2 years for diagnosis and 49% were diagnosed with other conditions prior to NETs, most often asthma (50%) and pneumonia (40%). At the time of diagnosis, 73% of lung tumors were in situ and 78% were surgically removed. Lung NET pts were more likely to be given the impression their cancer was curable (27%) or benign (19%) vs GI/pNET (8%/8% or 6%/8%). Following diagnosis, only 44% of lung NET pts were satisfied they received answers to questions or felt they had sufficient information (36%). Most (64%) expressed a need for more immediate access to NET health care providers (HCPs) (vs GI [53%]; pNET [45%]). Overall, pts with lung NETs had more negative feelings than pts with other NET types regarding HCP expertise/knowledge and quality of care. 36% regarded the quality of available treatments as poor/very poor (vs GI [26%]; pNET [27%]) and were the least likely (29%) to participate in clinical trials (vs GI [48%]; pNET [47%]). Lung NET pts also had a less close relationship with HCPs, had lower confidence in their NET team, felt they received less emotional support, and had the most questions. As with GI/pNET (73%/70%), most lung NET pts (66%) experienced a moderate/large negative impact on quality of life but were more likely to desire better access to NET experts/specialty centers. Conclusions: This large global pt survey demonstrated the substantial burden a lung NET diagnosis entails and identified areas for improvement.
A phase II study of lenalidomide as initial treatment of elderly patients with chronic lymphocytic leukemia.
Authors: X. Badoux, W. G. Wierda, S. M. O'Brien, S. Faderl, Z. Estrov, K. A. Yerrow, M. J. Keating, A. Ferrajoli
Journal: Journal of Clinical Oncology (2010)

6508 Background: Although the majority of patients (pts) with CLL are over the age of 70 years, there is no established standard therapy for this population. Based on the clinical efficacy demonstrated in pts with relapsed or refractory CLL, we explored the activity of lenalidomide as front-line monotherapy in elderly pts with CLL. Methods: Sixty pts were enrolled in this phase II study. All pts were age ≥ 65 years with untreated CLL/SLL and had indications for therapy by 1996 NCI-WG criteria, adequate performance status and renal/liver function prior to therapy. Treatment consisted of lenalidomide at 5 mg po daily for the first 56 days then titrated up to 25 mg/day as tolerated by 5 mg increments every cycle (28 days). Responses were assessed after 3 cycles and every 6 cycles thereafter. Results: All 60 pts are evaluable for response and toxicity. Median age was 71 years (range, 66-85). 18 pts had Rai stage III-IV disease, 20 pts had deletion of 17p or 11q by FISH analysis and 33 of 55 pts had unmutated IgVH genes. The overall response (OR) rate for all pts is 60%. 5 pts (8%) achieved a complete response (CR), 5 (8%) a nodular partial response (nPR) and 26 (43%) a PR. Response rates after 3, 9, 15 and 21 cycles are shown in the table. 56 pts (93%) are alive and 37 pts (62%) remain on lenalidomide. Median time to treatment failure has not been reached with a median follow-up of 19 months. We observed a rise in median IgG levels from 724 mg/dl at baseline to 941 mg/dl after 15 cycles of therapy (p<0.001). Grade (G) 3-4 neutropenia, thrombocytopenia, and anemia were noted in 35%, 4%, and <1% of cycles; G3-4 infections in 7% of pts. There was no G3 or 4 tumor lysis or tumor flare reactions whereas 30 pts experienced G1-2 tumor flare. Conclusions: Therapy with the immunomodulatory agent lenalidomide is safe and induces both CR and PR in elderly patients with untreated CLL. Best responses are observed after 9 cycles of therapy. The most common lenalidomide-associated toxicity is neutropenia. 3 cycles 9 cycles 15 cycles 21 cycles Number evaluable 59 60 54 39 NCI RESPONSE Number (%) CR 0 1 (2) 3 (6) 4 (10) Nodular PR 0 6 (10) 4 (7) 4 (10) PR 24 (41) 26 (43) 24 (44) 15 (38) OR 24 (41) 33 (55) 31 (57) 23 (59) Stable disease 26 (44) 6 (10) Failed or discontinued 9 (15) 21 (35) 23 (43) 16 (41) Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Celgene Celgene Biogen Idec, Celgene, Genentech, Genzyme
Arteriovenous malformations in hereditary haemorrhagic telangiectasia: looking beyond ALK1-NOTCH interactions
Authors: Hanna M. Peacock, Vincenza Caolo, Elizabeth A.V. Jones
Journal: Cardiovascular Research (2015)

Hereditary haemorrhagic telangiectasia (HHT) is characterized by the development of arteriovenous malformations--enlarged shunts allowing arterial flow to bypass capillaries and enter directly into veins. HHT is caused by mutations in ALK1 or Endoglin; however, the majority of arteriovenous malformations are idiopathic and arise spontaneously. Idiopathic arteriovenous malformations differ from those due to loss of ALK1 in terms of both location and disease progression. Furthermore, while arteriovenous malformations in HHT and Alk1 knockout models have decreased NOTCH signalling, some idiopathic arteriovenous malformations have increased NOTCH signalling. The pathogenesis of these lesions also differs, with loss of ALK1 causing expansion of the shunt through proliferation, and NOTCH gain of function inducing initial shunt enlargement by cellular hypertrophy. Hence, we propose that idiopathic arteriovenous malformations are distinct from those of HHT. In this review, we explore the role of ALK1-NOTCH interactions in the development of arteriovenous malformations and examine a possible role of two signalling pathways downstream of ALK1, TMEM100 and IDs, in the development of arteriovenous malformations in HHT. A nuanced understanding of the precise molecular mechanisms underlying idiopathic and HHT-associated arteriovenous malformations will allow for development of targeted treatments for these lesions.
A proof-of-concept (PoC) phase II criterion in a noninferiority context with application in patients with metastatic renal cell carcinoma (mRCC).
Authors: N. Hollaender, N. Rouyrre, B. Neuenschwander, M. Branson, T. Haas, E. Schiff, A. C. Kay, D. E. Lebwohl, E. Zuber
Journal: Journal of Clinical Oncology (2010)

e15055 Background: Single arm phase II studies provide limited information with respect to the efficacy of new treatments. A randomized phase II study using PFS as endpoint allows a more reliable PoC for further development of the new treatment in phase III. A PoC phase II design is proposed to establish the non-inferiority of a new treatment compared to a control treatment. Methods: A Bayesian PoC phase II design is proposed with the objective to have (1) a reasonably promising effect (treatment vs. control) estimate, and (2) good evidence that the treatment is better than a predefined non-inferiority margin. For (1) clinical input is required in order to implement an explicit rejection bound for the estimated effect, e.g. the maximum observed hazard ratio (HR) which could be still considered as similar to 1 (HR=1 means no treatment difference). The design is applied in the RECORD-3 (Renal cell cancer treatment with oral RAD001 given Daily) trial comparing the treatment sequence everolimus