tbuckley/cabot-search huggingface dataset:
Twin relationships and depression
Authors: M Paluszny, M L Selzer, A Vinokur, L Lewandowski
Journal: American Journal of Psychiatry (1977)

The authors investigated closeness and other variables measuring depression in 22 identical and 13 fraternal twin pairs. Each twin rated him/herself on a two-part questionnaire; part 1 included questions on demographic characteristics and the twin relationship, and part 2, the Zung Self-Rating Depression Scale, measured depressive symptoms. There was a high degree of agreement across all variables for the total sample, and degrees of depression were comparable to that in the general population. Closeness was found to be inversely correlated with depression. The authors suggest that future studies include other groups (siblings, spouses, etc.) and follow-up data.
Effect of combined therapy with temsirolimus (CCI-779), temozolomide (TMZ), and radiation (RT) in newly diagnosed glioblastoma multiforme (GBM) patients on immune suppression: Results from NCCTG N027D.
Authors: J. N. Sarkaria, E. Galanis, M. P. Gustafson, A. B. Dietz, W. Wu, P. D. Brown, J. H. Uhm, C. Giannini, K. A. Jaeckle, J. C. Buckner
Journal: Journal of Clinical Oncology (2010)

2016 Background: CCI-779 therapy concurrent with TMZ/RT and with adjuvant TMZ was associated with serious infections on the phase I trial N027D. In a modified trial, CCI-779 was given only during RT/TMZ, and immune system profiling was performed at multiple times. Methods: 13 patients were treated with CCI-779 50 mg IV weekly with concurrent TMZ 75 mg/m2 daily during RT, then TMZ alone at 200 mg/m2 days 1-5 q28 days for 6 cycles. Bloods for immune profiling were obtained at baseline, last week of CCI-779 therapy, and prior to the first and third cycles of adjuvant TMZ. Leukocytes were analyzed by FACS and compared by a paired rank-sum test. Results: CCI-779 during RT/TMZ was well tolerated without serious infections. However, 1 patient with pre-existing onychomycosis developed systemic dermatophytosis, and 1 patient developed herpes zoster. Levels of CD3+ T-cells and CD19+ B-cells were suppressed from baseline at all subsequent time points to 46%-74% and 29%-49%, respectively. Compared to baseline, CD4+ T-helper cells were lower at all subsequent time points (46%- 47% of baseline, p < 0.05; median levels 387 to 396 cell/uL), while CD8+ cytotoxic T-cells were lower only during and immediately following CCI-779 therapy (37%-50% of baseline, p < 0.05). CCI-779 therapy also was associated with a significant increase in regulatory T-cells seen only at the second time point (334%, p < 0.05). Natural killer (NK) cells and CD4 central memory cells were lower only at the second time point (52% and 60%, respectively; p < 0.05). Compared to normal donors, circulating monocytes were suppressed at baseline and did not change during the course of therapy. Conclusions: Combined therapy with CCI-779, TMZ and RT had profound effects on multiple immune system compartments. CCI-779 therapy was specifically associated with suppression of cytotoxic T-cells, central memory T-cells, and NK cells and elevation of regulatory T-cells. These results illustrate the potential for enhanced immunosuppression with rapalogs or second generation mTOR/PI3K inhibitors in combination with TMZ in GBM patients. Supported by CA25224 and CA114740. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Wyeth Wyeth
Phase II study of bevacizumab in combination with cisplatin and docetaxel as first-line treatment of patients (p) with metastatic non-squamous non-small cell lung cancer (NSCLC)
Authors: N. Ferrer, M. Cobo, A. Paredes, M. Méndez, J. Muñoz-Langa, A. Rueda, M. Álvarez de Mon, A. Sánchez-Hernández, R. Gallego, J. Torrego
Journal: Journal of Clinical Oncology (2009)

e19023 Background: Bevacizumab (B), in addition to platinum-based chemotherapy, is indicated for 1st-line treatment of p with advanced NSCLC other than predominantly squamous cell histology. B has been shown to improve progression free survival (PFS) and overall survival (OS) when combined with cisplatin/gemcitabine and carboplatin/paclitaxel, respectively. However, there are limited data on the safety and efficacy of B in combination with other widely used chemotherapy doublets for NSCLC. This is a single-arm, open- labeled, single-stage phase II trial of cisplatin (C), docetaxel (D) and B for NSCLC. Methods: Eligibility criteria: chemo- naïve, stage IIIB wet or IV, non-squamous NSCLC, PS 0–1, no brain metastases and no history of gross hemoptysis. P received D (75 mg/m 2 ), C (75 mg/m 2 ), and B (15 mg/kg iv) on day 1 every 3 weeks for up to 6 cycles, followed by B 15 mg/kg alone every 3 weeks until disease progression or toxicity. Primary endpoint: PFS. Results: 50 p were enrolled (enrollment completed): 24% female, median age 60 (36–74), PS 1: 64%, adenocarcinoma: 72%; stage IV: 92%. Two p did not start treatment. Median follow-up is 5.3 months (range 0–13.6). Median number of cycles of B was 7 (range 0–18). 56% completed 6 cycles of treatment; 24% received ≥ 12 cycles of B. Most frequent grade ≥ 3 toxicities: diarrhea (14.6%), fatigue (14.6%), dyspnea (9.8%), anorexia (4.9%), alopecia (4.9%), esophagitis (4.9%), constipation (4.9%), mucositis (12.2%), proteinuria (4.9%); hematological toxicities: neutropenia (22%), febrile neutropenia (9.8%), leucopenia (14.6%), lymphopenia (4.9%). Of interest, 41.5% developed grade &lt;3 epistaxis and 17% hypertension (1 p grade 3). One p died due to hemoptysis. 46 p were evaluable for response: 29 PRs (ORR: 63%). 18 of 48 p have experienced progression or death with a median SLP of 7.8 months (95% CI: 6.6-NR). Median OS is 13.5 months (95% CI: 12.7–13.6; 81.2% p censored); 1-year survival is 83.9% (95% CI: 67.4%-92.5%). Conclusions: Treatment with C, D and B, followed by maintenance B in 1 st line of advanced non-squamous NSCLC shows an acceptable toxicity profile and promising efficacy. Final results will be presented. [Table: see text]
KRAS and BRAF mutational status and PTEN, cMET, and IGF1R expression as predictive markers of response to cetuximab plus chemotherapy in metastatic colorectal cancer (mCRC).
Authors: M. Di Salvatore, A. Inno, A. Orlandi, M. Martini, G. Nazzicone, D. Ferraro, A. Astone, A. Cassano, L. Larocca, C. Barone
Journal: Journal of Clinical Oncology (2010)

e14065 Background: KRAS and BRAF mutations are associated with resistance to cetuximab in mCRC. Reduced PTEN expression or over-expression of cMET and IGF1R with activation of cell cascade signaling could represent further mechanisms of resistance to EGFR-blockade. Methods: We retrospectively correlated KRAS and BRAF mutational status and PTEN, cMET and IGF1R expression with the clinical outcome of 60 patients (pts) treated with cetuximab plus chemotherapy in front-line setting or as further line therapy. Results: 23/60 (38.3%) pts were KRAS mutated. 23 of 37 KRAS wild-type pts were evaluated for BRAF and no mutations were found. Reduced PTEN expression was found in 7 (11.7%) while an iperexpression of cMET and IGF1R was found in 40 (72.7%) and in 15 (27.3%) pts, respectively response rate (RR), time to progression (TTP) and overall survival (OS) in KRAS mutated and KRAS wild-type pts were 0% and 24.3% (p = 0.01), 2 and 5 months (p = 0.036), 8 and 13 months (p = 0.015). No difference was observed in terms of TTP and OS according to PTEN status; although not significantly, RR was higher in pts with normal PTEN (12.5%) compared with those with reduced PTEN expression (0%). Pts with low or normal cMET expression achieved a higher RR (26.7% vs. 7.5%, p = 0.079) with a significantly longer TTP (5 vs. 3 months; p = 0.028) and a trend toward a longer OS (p = 0.099) in comparison with pts with a cMET iperexpression. In pts with a higher and with normal/lower IGF1R expression, RR was 20% and 10% (p = 0.376), TTP 5 and 4 month (p = 0.074), respectively; a significantly longer OS was observed in higher versus lower/normal IGF1R expression (24 vs. 10 months; p = 0.036). Conclusions: KRAS mutations are the strongest negative predictive marker of response to cetuximab treatment in mCRC. A cMET iperexpression is related to resistance to cetuximab. Despite a trend of higher RR in pts with normal PTEN, the role of PTEN expression should be further investigated. Interestingly, a IGF1R iperexpression is not associated with resistance to cetuximab but it seems to represent a favorable prognostic factor in mCRC. No significant financial relationships to disclose.
Effect of infliximab and methotrexate on radiographic progression in patients with early rheumatoid arthritis
Authors: D Van der Heijde, Patrick Durez, P. Emery, E Keystone, RN Maini, Kalden, M. Schiff, J. Han, D. Baker, J. Smolen, E St Clair
Journal: Annals of the Rheumatic Diseases (2005)
Anti-proliferative and molecular effects of neoadjuvant (pre-operative) gefitinib alone or in combination with anastrozole in epidermal growth factor receptor (EGFR) positive, estrogen receptor alpha (ERα) positive patients with primary breast cancer
Authors: A. Polychronis, H. D. Sinnett, D. Hadjiminas, H. Singhal, J. L. Mansi, S. Ali, M. J. Slade, S. Shousha, K. Morrisson, R. C. Coombes
Journal: Journal of Clinical Oncology (2005)

552 Background: We conducted a study to determine the effects of EGFR inhibition with or without aromatase inhibition, on the growth of primary breast cancer. Estrogen and epidermal growth factor phosphorylate ERα via MAPK. This trial used inhibition of EGFR alone vs ER + EGFR inhibition in ER+/ EGFR+ breast cancer to determine the role for EGFR in modulating both the Ser118 phosphorylated (p) state of ERα and downstream events (cell proliferation (Ki67) / tumour size). Methods: 53 untreated postmenopausal patients with ER+/EGFR+ primary breast cancer were randomised to 4 wks neoadjuvant therapy with gefitinib (Iressa) alone (Group A) or gefitinib + anastrozole (Group B) in a controlled double-blind trial. Biopsies were collected before & after 4 wks treatment. Expression of Ki-67, pEGFR (Y845), MAPK, AKT and pERα (S118) was assessed by immunohistochemistry in paired samples. Tumour size and pharmacokinetics were also evaluated. Results: Ki67 was reduced by 77.3 and 93.2% in Groups A and B respectively, indicating a greater reduction in Group B (p=0.008). Radiological size, pEGFR and pER, whilst significantly reduced in both arms (p<0.0001), were no different between groups A and B. P value determined using Mann Whitney U test comparison of reduction Group A vs Group B using ITT analysis set. Conclusions: Suppression of EGFR using gefitinib alone is an effective inhibitor of both EGFR and ERα phosphorylation, significantly inhibiting cell proliferation & tumour growth. Direct inhibition of ER receptor activity in addition to EGFR inhibition induced a further significant reduction in Ki67 greater than getifinib alone, suggesting that ER & EGFR control proliferation through dual and independent signalling pathways. Further analysis of downstream signal transduction mediators (MAPK, AKT) will be presented. Reduction in biomarkers and tumour size at 4 wks from baseline Group A (mean ± SEM) P value (Intragroup) Group B (mean ± SEM) P value (Intragroup) P value (Intergroup) Ki-67 (% reduction from baseline) −77.3 ± 5.9 [n=27] <0.0001 −93.2 ± 2.3 [n=26] <0.0001 0.008 Radiological size (% reduction from baseline) −30.3 ± 4.9 [n=26] <0.0001 −28.8 ± 3.6 [n=21] <0.0001 NS pEGFR (absolute changes in values) −1.7 ± 0.19 [n=27] <0.0001 −1.3 ± 0.2 [n=26] <0.0001 NS pER∝ (S118) (absolute changes in values) −1.4 ± 0.2 [n=27] <0.0001 −1.69 ± 0.2 [n=26] <0.0001 NS Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca UK Ltd. AstraZeneca UK Ltd.
Efficacy of Therapeutic Dose Versus Prophylactic Dose of Anticoagulants in the Primary Prevention of Thrombotic Events in Ambulatory Patients with Solid Malignancies Receiving Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Nay Min Tun, Elizabeth Guevara, Thein H. Oo
Journal: Blood (2014)
Expression and prognostic significance of X-ray crosscomplementation group 1 (XRCC1) in head and neck squamous cell carcinoma patients undergoing concurrent chemoradiation.
Authors: M. Ang, N. Zhao, M. Hayward, M. Patel, X. Yin, M. D. Wilkerson, W. K. Funkhouser, K. Fritchie, A. Olshan, D. N. Hayes
Journal: Journal of Clinical Oncology (2010)

5541 Background: As x-ray crosscomplementation group 1 (XRCC1) is involved in base excision repair, single strand break repair and repair of DNA damage from chemotherapy and radiotherapy, it may influence the response to chemoradiotherapy (CRT). We examined the expression and prognostic significance of XRCC1 in head and neck squamous cell carcinoma (HNSCC) patients. Little is known about this gene in HNSCC. Methods: We constructed triplicate-core tissue microarrays (TMA) from 143 unselected consecutive HNSCC patients diagnosed at our institution from 2002 through 2006. Expression of XRCC1 was assessed by immunohistochemistry. XRCC-high vs. XRCC-low status was determined using the median H score as the cutoff- the H score (range 0-300) being the product of staining intensity (0-3) and percentage of nuclei stained (0-100). Differences in survival were calculated using log rank (LR) statistics. Results: Patients were treated with surgery only (n=32), radiation only (16), surgery and radiation (22), surgery and adjuvant CRT (19), primary CRT (53) and palliative measures (1). Median follow-up time was 67 months (range 40-88 months) with median overall survival of 68 months. Almost all patients (97.8%) showed staining for XRCC1 with median H score of 240. XRCC-high and XRCC-low patients were similar in mean age, gender, pack years smoked, proportion of stage III/IV cases and primary tumor site distribution. Overall, XRCC-high status showed a trend towards poorer cancer-specific survival (mean survival (MS) 52 vs. 62 months, p=0.12). Strikingly, this benefit appeared entirely limited to patients undergoing CRT (n= 68, MS 65 vs 45 months, LR p value = 0.02) whereas there were no differences in survival in patients being treated by non-CRT modalities (n=70, MS 59 vs. 56 months, LR p = 0.89). In a multivariate Cox regression model, XRCC-high status in CRT patients was associated with poorer cancer-specific survival, independent of stage and tumor site (hazard ratio = 2.60, p=0.01). Conclusions: XRCC expression is common in HNSCC. High expression of XRCC1 is associated with poor survival in HNSCC patients undergoing CRT and warrants further investigation. No significant financial relationships to disclose.
Multidimensional Geriatric Assessment reveals unknown medical problems in elderly cancer patients (pts)
Authors: C. Terret, G. Albrand, J. P. Droz
Journal: Journal of Clinical Oncology (2004)

8167 Background: Aging is highly heterogeneous. Standard medical assessment is not effective to describe elderly pts' medical problems that may affect or interact with cancer. Comprehensive Geriatric Assessment is the recommended tool of evaluation. Methods: We have elaborated a "minimal" Comprehensive Geriatric Assessment (mini-CGA). This procedure is performed by a trained team including a geriatrician, a medical oncologist, a social worker, a dietician, a physiotherapist, a pharmacist and a research nurse. It is based on a careful clinical examination with analysis of physical function, nutritional status (MNA), functional domains (ADL, IADL), cognitive and emotional domains (MMSE, GDS), identification and grading of comorbidity (CIRS-G), socioeconomic evaluation and a medication review. The final step of the procedure is the synthesis of all information and its translation into a geriatric intervention plan. Results: One hundred and thirty five cancer pts were assessed by means of mini-CGA. Median age was 78 (range 66–92). There were 93 males and 42 females. Main tumor types were urogenital (70), breast (19), head and neck (15), gastrointestinal (7), lung (4) cancers and lymphoma (3); 66% of pts had advanced disease. Only 35.6% lived alone and 64.4% had a reliable caregiver. Eighty-three percent pts had KPS ≥60% (median KPS: 70%), only 44% pts were fully independent in ADLs (score = 6), and 13.3% pts in IADLs (score = 14). Only 45.2% had no cognitive disorder (MMSE >24/30); 51.2% had no depression symptom (GDS <10/30). Only 35.6% pts were well-nourished (MMA >23.5), and 23.7% were already malnourished (MMA <17). All pts had at least 1 comorbidity, with a median of 7 (range: 1–14) and a median number of severe comorbidities of 1 (0–9). Pts took a median of 5 medications (range: 0–15). We identified 30 cases of dangerous drug interactions. By means of mini-CGA, only 4 pts were identified as healthy elderly pts. Conclusions: Unsuspected health problems can be detected by mini-CGA in elderly cancer pts. This tool can be applied in oncology setting without specific instruments. However, it must be compared to screening tools and to extensive CGA. No significant financial relationships to disclose.
Could treatment with tamoxifen be superior to aromatase inhibitors in early-stage breast cancer after pharmacogenomic testing? A modeling analysis
Authors: R. S. Punglia, E. P. Winer, J. C. Weeks, H. J. Burstein
Journal: Journal of Clinical Oncology (2007)

502 Background: Adjuvant endocrine treatment with upfront aromatase inhibitors yields improved disease-free survival compared to tamoxifen in unselected women with estrogen receptor-positive breast cancer. However, levels of endoxifen, the active tamoxifen metabolite, are known to vary with the number of mutant alleles of the cytochrome P450 CYP2D6 enzyme. We created a Markov model to examine whether the optimal treatment strategy for patients with wild type genetics (wt/wt) might differ from that for patients with homozygous (*4/*4) or heterozygous (wt/*4) mutations. Methods: Annual recurrence risks with aromatase inhibitors and tamoxifen in unselected women were taken from the BIG 1–98 trial. Based on data from Goetz et al., we assumed that the percent of patients who are homozygous and heterozygous for mutations are 6.8% and 21.1%, respectively, and that the hazard ratio (HR) for increased cancer recurrence on tamoxifen among *4/*4 carriers is 1.86 relative to patients with wt/wt or wt/*4 genotypes. Because the efficacy of tamoxifen among wt/*4 patients is not known, we tested the full possible range, from efficacy same as wt/wt patients (Ehet=0) to that of *4/*4 mutation carriers (Ehet=1). Results: In the unselected group, 5-year disease-free survival (5-DFS) with aromatase inhibitors and tamoxifen was 0.840 and 0.813, respectively. Under baseline assumptions, tamoxifen is more effective than aromatase inhibitors among wt/wt patients as long as the effect in heterozygotes is at least 54% (Ehet=0.54) of that in *4/*4 patients. With increasing HR for *4/*4 patients, tamoxifen estimates exceed those of aromatase inhibitors in the wt/wt cohort even at lower assumed Ehet ratios (see table ). Conclusion: In patients without CYP2D6 mutations, modeling suggests that initial treatment with tamoxifen could be superior to treatment with aromatase inhibitors, supporting the use of genetic testing to determine the optimal treatment strategy. [Table: see text] No significant financial relationships to disclose.
Nephroprotective role of magnesium salt in cisplatin-induced renal damage in patients with ovarian cancer
Authors: G. Wcislo, L. Bodnar, C. Szczylik
Journal: Journal of Clinical Oncology (2008)

16532 Background: Cisplatin is an effective antineoplastic agent, but can cause renal tubular damage. The experimental studies indicate a substantial additive effect of Mg- depletion on cisplatin induced renal toxicity. The aim of this study was to examine the effect of magnesium supplementation on nephrotoxicity after giving the standard cisplatin- based chemotherapy in patient with epithelial ovarian cancer (EOC). Methods: A double-blind, placebo- controlled, randomised study conducted in which magnesium sulphate was administered at a dose of 5 g as an iv infusion before each of course of standard chemotherapy with paclitaxel 135 mg/m2 over 24 h infusion plus cisplatin 75 mg/m2 (PP) every 3 weeks in patients with EOC. Between each of courses and 3 weeks after six of this regiments the patients were administered magnesium subcarbonate at a dose 500 mg three times per day p.o. GFR markers as: serum levels of creatinine, creatinine clearance estimated on Cocroft- Gault (ClCG) and Modification Diet of Renal Disease (MDRD1) formula were recorded before the starting each of the cycles, and 3 weeks after the sixth course. Results: Between January 2003 and January 2006, 41 EOC patients who underwent randomization, 40 were eligible. We noted that serum levels of magnesium significantly varied between supplemented and non- supplemented groups (p<0.0001). The placebo (control) group showed significantly greater slope of GFR assessed by: serum levels of creatinine (p=0.0069), creatinine clearance estimated on Cocroft- Gault (p=0.0077) and MDRD1 (p=0.032) formula than magnesium supplemented group. Neither group showed differences in tumor growth rates or outcome. Conclusions: These results show that magnesium supplementation during chemotherapy with Cisplatin/ Paclitaxel is a nephroprotective management with no reduction of antitumor efficacy. No significant financial relationships to disclose.
Effect of GM-CSF on tumor-specific immune response and antitumoral efficacy when combined with suicide gene therapy
Authors: H. Akbulut, A. Coleri, N. Acikgoz, G. Sahin, P. Ozkal, Y. Tang, F. Icli, A. Deisseroth
Journal: Journal of Clinical Oncology (2009)

e14610 Background: Suicide gene therapy is one of the promising treatment modalities in cancer treatment. Combination of an immunotherapy modality with suicide gene therapy would increase the tumor eradciating efficacy of either treatment strategy used alone. Methods: In the current study, we constructed adenoviral vectors carying ytosine deaminase (CD), granulocyte macrophage-colony stimulating factor (GM-CSF) vectors. We tested the in vitro efficacy of the vectors in both human and mouse tumor cell lines and in a syngeneic mouse model of colon cancer with tumor explants of CRL 2638 cells. Results: Our results show that the vectors carrying CD/GM-CSF transcription units are effective in terms of killing of tumor cells when 5-FC added. Addition of GM-CSF transgene induced a significant amount of GM-CSF secretion (250 pg/ml/105 cells) of infected cells. In the syngeneic colon cancer model, addition of GM-CSF significantly increased tumor-specific cellular immune response when compared to suicide gene therapy alone. (p&lt;0.01). Likewise, GM-CSF addition caused a 8 times reduction in the ratio of Tregs infiltrating the tumor nodules (p&lt;0.001). Accordingly, GM-CSF decreased the tumor growth by 2 times an d increased the median survival time by 50% (p&lt;0.01). Conclusions: These impressive results of in-vitro cytotoxicity and encouraging results of in-vivo testing of the our newly constructed GM-CSF carrying vector suggest a potential for the use of the vector for the treament of established tumors by inducing tumor specific immune response. No significant financial relationships to disclose.