tbuckley/cabot-search huggingface dataset:
Corticosteroid-induced magnetic resonance imaging changes in patients with recurrent malignant glioma.
Authors: C J Watling, D H Lee, D R Macdonald, J G Cairncross
Journal: Journal of Clinical Oncology (1994)

PURPOSE We studied corticosteroid-induced magnetic resonance (MR) scan changes in patients with recurrent malignant glioma to determine if corticosteroid therapy started concurrently with investigational treatment might yield false-positive responses. PATIENTS AND METHODS Ten symptomatic patients not on corticosteroids when malignant glioma recurred had a baseline MR scan performed before corticosteroid treatment, followed by serial scans at weekly intervals for 1 month while on dexamethasone (16 mg/d). The maximum cross-sectional areas and volumes of the gadolinium-enhancing regions (tumor) and T2-weighted abnormalities (tumor plus edema) were compared quantitatively and qualitatively for each series of scans. RESULTS Nine of 10 patients (90%) had a measurable reduction in the size of the gadolinium-enhancing region or T2-weighted abnormality with corticosteroid treatment. The maximum cross-sectional area and volume of the gadolinium-enhancing region decreased by at least 25% in three of 10 patients (30%). The maximum cross-sectional area and volume of the T2-weighted abnormality decreased by at least 25% in five of 10 patients (50%). Maximum measurable radiologic improvement was evident within 2 weeks in most patients. MR scans were judged improved by the reporting neuroradiologist in seven of 10 (70%). These subjective visual improvements were also evident within 2 weeks, but generally described as slight or modest. CONCLUSION Corticosteroid-induced MR scan reductions in tumor size may confound the assessment of response of recurrent malignant gliomas to investigational agents. For patients who start corticosteroids for symptom control, investigational treatment should be delayed until a new baseline MR image is established 2 weeks later. Response is then judged by comparing subsequent MR scans with the new corticosteroid-influenced baseline image.
Perinatal Difficulties, Head and Face Trauma, and Child Abuse in the Medical Histories of Seriously Delinquent Children
Authors: Dorothy Otnow Lewis, Shelley S. Shanok, David A. Balla
Journal: American Journal of Psychiatry (1979)

The authors compared the medical histories of incarcerated and nonincarcerated delinquent children. Incarcerated delinquent children were significantly more likely than nonincarcerated delinquents to have sustained severe head and face injury. Differences were evident by age 2. Perinatal difficulties and psychiatric impairment were also significantly more prevalent in the histories of incarcerated delinquents. Especially violent incarcerated children had more perinatal difficulties, accidents, injuries, and ward admissions than did their less violent incarcerated peers. The authors suggest that the combination of early CNS trauma, parental psychopathology, and social deprivation is responsible for the serious, often violent, delinquency that is now prevalent.
Prospective observational study on the use of buprenorphine in patients with palliative cancer.
Authors: P. M. Clement, B. L. M. Beuselinck, G. Mertens, P. Cornelissen, J. Menten
Journal: Journal of Clinical Oncology (2011)

e19564 Background: Transdermal buprenorphine has also proven effect on neuropathic pain and is of interest for the management of pain in palliative cancer patients. An expert panel found that the use of higher doses than those recommended in the prescribing information may be warranted though there is insufficient evidence. The need and value of high dose buprenorphine are assessed. Methods: Prospective observational study. Patients attending the department of oncology and/or the department palliative care who suffer pain and would normally be offered transdermal treatment with buprenorfine. 36 patients were given full information and asked to sign informed consent. The primary outcome parameter was the patient’s report of pain intensity, and side effects. Where possible the need for breakthrough medication was documented. Results: 36 patients signed the informed consent. 5 patients never started buprenorfine treatment and 3 patients stopped immediately after the first application of the patch. 28 patients received buprenorfine for at least 3 days. Pain control was achieved in 21 out of 28 evaluable patients. In two patients, the dose was increased to 210 and 175 µg/hr. Two patients were switched to fentanyl TDD when the 140 µg/hr dose buprenorfine did not provide a satisfactory outcome. Transdermal buprenorfine is an efficient analgesic achieving adequate pain control in the majority of patients. In this observational prospective study that represents daily practice, 1/7 patients required doses higher than 140 µg/h. 36 patients signed the informed consent. 5 Patients never started buprenorfine treatment and 3 patients stopped immediately after the first application of the patch. 28 patients received buprenorfine for at least 3 days. Pain control was achieved in 21 out of 28 evaluable patients. In two patients, the dose was increased to 210 and 175 µg/hr. Two patients were switched to fentanyl TDD when the 140 µg/hr dose buprenorfine did not provide a satisfactory outcome. Conclusions: Transdermal buprenorfine is an efficient analgesic achieving adequate pain control in the majority of patients. In this observational prospective study that represents daily practice, 1/7 patients required doses higher than 140 µg/h.
Epidermal growth factor receptor (EGFR) serum level may predict response in patients with advanced colorectal cancer (ACC) treated with gefitinib
Authors: M. G. Zampino, E. Magni, L. Zorzino, L. Santoro, C. Massacesi, A. Zaniboni, F. Di Clemente, A. Martignetti, S. Boselli, F. de Braud
Journal: Journal of Clinical Oncology (2007)

4119 Background: EGFR-overexpression reported in colorectal cancer, justifies use of EGFR inhibitors. We conducted a phase II study (ESMO 2005) in ACC with the aim to assess efficacy of gefitinib plus oxaliplatin containing regimen. Main biological objective was to assess serum EGFR extra-cellular binding domain as surrogate marker of tyrosine-kinase inhibition and as predictor of outcome. Methods: 57 patients with EGFR-positive ACC,received gefitinib 250 mg/day combined with simplified FOLFOX-6 for at least 4 cycles,for a maximum of 10 courses.In not progressive disease, gefitinib was continued as maintenance treatment. Tumour assessment by RECIST criteria was performed at baseline and every 4 cycles.Serum EGFR extracellular binding-domain was evaluated by quantitative enzyme-linked immunoadsorbent.Serum EGFR as predictive factor was evaluated both taking into account the basal value only,and the whole EGFR pattern over time.The analyses were performed by logistic and Cox’s regression model with time-dependent covariate respectively;both models included centre, gender,age and site of primary tumours as adjusting factors. Results: Serum samples for EGFR were obtained at baseline and at every assessment.During mono-therapy phase the patients with serum samples decreased. Over treatment,34 patients reported a CR or PR as best objective response (BOR),while 9 patients showed SD or PD. Higher serum EGFR was associated to BOR both at baseline and over time.This result was confirmed by a similar analysis,which considered the whole EGFR profile,instead of the basal value only. Conclusions: Serum EGFR at baseline can be considered a significant predictor for the BOR.This observation is in line with data reported on lung cancer (Gregorc V, 2004).Although the EGFR trend over time seems to confirm the basal difference,this result should be taken with caution,due to the little number of cases reporting EGFR values besides the basal one. [Table: see text] No significant financial relationships to disclose.
Circulating tumor cells (CTC): A reliable predictor of treatment efficacy in metastatic breast cancer (MBC)
Authors: M. C. Liu, C. Isaacs, R. Warren, P. Cohen, M. Wilkinson, Y. Ottaviano, S. Rao, Y. Zhang, A. Gallagher, P. G. Shields
Journal: Journal of Clinical Oncology (2008)

11018 Background: ≥5 CTC/7.5 mL blood is associated with worse progression free survival (PFS) and overall survival (OS) in MBC. The persistence of ≥5 CTC/7.5 mL blood appears to predict for treatment failure. We are conducting a prospective clinical trial with long term follow-up to validate the prognostic and predictive significance of this biomarker in MBC. Methods: Serial CTC levels are obtained in patients starting a new systemic regimen for progressive, radiographically measurable MBC. 10 mL samples of peripheral blood are collected at the start of treatment and then at 3–4 week intervals. CTC enumeration is performed on a 7.5 mL blood volume using the CellSearch technology (Veridex, LLC; Warren, NJ). Clinical outcomes are based on radiographic studies by RECIST criteria. All subjects are followed for PFS and OS, and they may continue CTC testing upon progression. Information on other tumor markers is incidentally collected during the study period and includes LDH, alkaline phosphatase, and the MUC-1 glycoprotein. Results: 73/100 subjects are currently on study. 50 have completed at least one radiographic staging evaluation, yielding 154 pairs of concurrent CTC values and imaging assessments. Treatment includes chemotherapy (34%), endocrine therapy (28%), and combination therapy with a biologic (38%). 60% of subjects have had at least one result of 0, 92% have had ≥1 (range 1–580), and 66% have had ≥5 CTC/7.5 mL. Disease progression occurred in 29% of cases with <5 CTC/7.5 mL and 69% of cases with ≥5 CTC/7.5 mL (p<0.0001). Correlating CTC and radiographic assessments from the same patient, ≥5 CTC/7.5 mL is associated with a 5.32 fold higher risk of disease progression (p<0.0001). In addition, ≥5 CTC/7.5 mL is associated with higher sensitivity and specificity than LDH, alkaline phosphatase, and the MUC-1 glycoprotein in predicting for disease progression in patients with measurable MBC. Conclusions: The odds of disease progression are 5.32 fold higher for patients with ≥5 than <5 CTC/7.5 mL blood. CTC levels should be used as a surrogate marker for treatment efficacy and disease responsiveness in both measurable and nonmeasurable disease, as they are a more reliable means of assessing treatment response than the traditional tumor markers currently in use. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Veridex, LLC Veridex, LLC Veridex, LLC
Functional heterogeneity of prostatic intra-epithelial neoplasia: Length of hormonal therapy influences response
Authors: T. Kang, P. Nichols, E. Skinner, S. Groshen, G. Valin, W. Ye, D. Raghavan
Journal: Journal of Clinical Oncology (2006)

4648 Background: Prostatic intraepithelial neoplasia (PIN) is a premalignant lesion of the prostate etiologically linked to prostate cancer. While androgen deprivation therapy (ADT) has been used to reduce prostate cancer, there are controversial data regarding the effect of ADT on PIN. We hypothesized that PIN is a heterogeneous entity with respect to hormone responsiveness, that this may explain aspects of the heterogeneity in the natural history of this disease, and have used the clinical model of ADT followed by radical prostatectomy as a test of this hypothesis. Methods: We performed a retrospective study on a cohort of patients who underwent prostatectomy with biopsy proven prostate cancer. Study patients were those who must have received at least 3 months of ADT at the discretion of their surgeons. Patients from the same cohort who did not undergo ADT were used as controls. Patients were randomly selected from the database and their pathology slides were reviewed by a blinded pathologist looking for presence of PIN with an independent observer. Fisher’s exact test was used to compare the proportions of subjects who had residual PIN in the study group and the control group. Exact logistic regression was used to evaluate the duration of ADT in PIN regression. Results: Eighteen patients initially diagnosed with PIN who did not receive hormonal therapy were identified; 28 patients with PIN who underwent hormonal therapy were also studied. All patients who did not receive hormonal therapy had residual PIN whereas 7 of 28 patients undergoing ADT had no residual PIN (p = 0.043). Evaluation of hormonal therapy between responders and non-responders showed statistically significant association between PIN regression and hormone therapy duration (p &lt; 0.001). However PIN response to ADT was not uniform as 16% of patients with ADT longer than 6 months had residual PIN, suggesting variable sensitivity of PIN to ADT. Conclusions: Our results demonstrate that ADT does cause PIN regression, and that there is heterogeneity in this effect with respect to hormonal duration. We propose for future prospective, multi-centered, randomized trials in which ADT impact on PIN is characterized further. No significant financial relationships to disclose.
A study of Irish cancer specialists’ opinions regarding sexual health for cancer patients
Authors: M. C. Colleran, M. Capra, S. Pattison, S. Higgins
Journal: Journal of Clinical Oncology (2008)

20673 Background: Quality of life is an important aspect of cancer care. Sexual health is a feature of quality of life. Cancer patients may experience neutropenia secondary to disease or treatment. Yet, there is an absence of data on the risks to cancer patients from sexual activity when neutropenic. The aim of this study is to determine present opinion and practice by cancer specialists in Ireland regarding the sexual health care of cancer patients. Method: A cross-sectional survey using a confidential, self-administered questionnaire was performed of all ‘113’ identified consultants (75) and specialists registrars (38) in medical and paediatric oncology, haematology and palliative care attached to major cancer centres in the Republic of Ireland. Two reminders were sent. Descriptive and content analysis were performed on the quantitative and qualitative data respectively. Results: 43 (response rate of 37.5%) replies were received. While the majority of respondents 23/14 discussed to varying degrees the possible impact of cancer and treatment on fertility with patients, if applicable, only 1 ’always’ discussed the possible impact of cancer on sexual activity. Opinions regarding the risk of sexual activity in patients included: infection risk to women with neutropenia, possible infection-risk benefit of condom-associated sexual activity, bleeding secondary to related thrombocytopenia. In some cases this questionnaire provided the first opportunity to consider such issues. Concern was raised about the adequacy of medical training regarding sexual health care of patients. Conclusions: Diversity in medical advice and opinions regarding possible risks to cancer patients and specifically with neutropenia from sexual activity are evident. The sensitive nature of sexual health counselling, in this cohort of patients, together with the paucity of evidence, proved limiting factors to therapeutic dialogue. Further research is necessary with the aim of providing evidence based patient care. No significant financial relationships to disclose.
Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from ovarian cancer: A multiinstitutional study of 246 patients
Authors: J. Bereder, O. Glehen, J. Habre, M. Desantis, E. Cotte, N. Mounier, I. Ray-Cocquard, B. Karimdjee, N. Bakrin, J. Bernard, D. Benchimol, F. Gilly
Journal: Journal of Clinical Oncology (2009)

5542 Background: Optimal treatment of chemoresistant and recurrent ovarian cancer is debating with second line chemotherapies. For peritoneal carcinomatosis new treatment combining cytoreductive surgery with heated intraperitoneal per operative chemotherapy (HIPEC) may improve survival. Methods: Retrospective bicentric study of 246 patients with peritoneal carcinomatosis from ovarian cancer were performed to evaluate HIPEC and to identify prognostic factors. Peritoneal Cancer Index (PCI) assess tumor load and completeness cytoreductive score (CCS) was used to give quality of resection CC0 (no visible tumor), CC1 (persistent diffuse lesions &lt; 2.5mm), CC2 (2.5mm &lt; CC2 &lt; 25mm) and over CC3 status. HIPEC is performed with platinum based regimen at 42°C. Endpoint was survival. Kaplan-Meier survival curve was fitted to the data. Cox's regression model was used for multivariate survival analysis. Results: The study included 268 procedures in 246 patients from 1991 to 2008. 206 procedures were performed in 184 patients with recurrence (Group 1) and 62 in chemoresistant patients (Group 2). After completion of resection the allocation of CCS was CC0 = 164, CC1 = 83, CC2 = 15, and CC3 = 5. Only 1 patient died in post operative course and procedure related morbidity rate was 12%. 5 years overall and free survival were respectively 35 % and 10%. Median overall survival was 49 months and the median disease free survival was 13 months. There was no difference between group 1 and 2 for survival. Independent prognostic factors for survival were the carcinomatosis extent, the completeness of cytoreductive surgery (HR = 2.26 IC95 [1.3–3.91]), performance status (HR = 4.3 IC95 [1.23–14.4]) and redo procedure (HR = 0.9 IC95 [0.001–0.9]). Conclusions: Hipec is a standardized and reproducible feasible method. Less extensive disease and the quality of cytoreduction remain an independent factor of better outcome. Morbidity is acceptable. To date in selected patients, HIPEC allows to reach the longest median time survival in recurrent peritoneal carcinomatosis from ovarian cancer. No significant financial relationships to disclose.
Inhibition of angiogenic activity in endothelial cells by blockade of the Renin-Angiotensin-system
Authors: D. Herr, M. Rodewald, H. M. Fraser, G. Hack, R. Konrad, R. Kreienberg, C. Wulff
Journal: Journal of Clinical Oncology (2008)

22026 Background: Efforts have been undertaken to find new ways to target tumor growth such as inhibition of angiogenesis. One of the main angiogenic regulators is vascular endothelial growth factor (VEGF). Thus, targeting VEGF by application of VEGF- antibodies has become an approach in anti-angiogenic therapy. Recently, we showed that the Renin-Angiotensin-System (RAS) not only controls the vascular tone but also regulates angiogenesis via influencing VEGF in breast cancer cells. Now, this further study was performed in order to investigate, whether the RAS directly influences the endothelium as well as endothelial proliferation, thus angiogenesis, itself. Methods: Human umbilical vein endothelial cells (HUVEC) were stained for Angiotensin II type 1 receptor (At1R) immunocytochemically and for gene expression of Renin-Angiotensin-System (RAS) components. Angiotensin II dependent regulation of VEGF and Angiopoietins (Ang-1 and Ang-2) was studied using quantitative RealTimePCR. Furthermore, we examined the effect of Angiotensin II on the proliferation of HUVEC using a ki-67 assay and investigated whether administration of At1R blocker candesartan, or VEGF antagonist Flt-1-Fc could suppress Angiotensin II dependent effects. Results: At1R, RAS-components and Ang-1/Ang-2 were expressed in HUVEC. Administration of Angiotensin II increased gene expression of VEGF and decreased the ratio of Ang1/Ang2 expression significantly. In addition, significantly increased endothelial cell proliferation was observed after stimulation with Angiotensin II, which was suppressed by simultaneous administration of candesartan or VEGF antagonist, Flt-1-Fc. Conclusions: These results indicate the potential capacity of Angiotensin II to influence angiogenesis by regulation of angiogenesis associated genes via At1R. Since VEGF blockade opposed the effect of Angiotensin II on cell proliferation, it is hypothesised that VEGF mediates the Angiotensin II-dependent effect in concert with changes in angiopoietin expression. This is the first report of the RAS in regulation of angiogenesis associated genes in endothelial cells indicating an involvement of At1R which may lead to new anti-angiogenic strategies via inhibition of this receptor. No significant financial relationships to disclose.
Accelerated partial breast irradiation with interstitial brachytherapy as the sole modality of radiation for women with low risk early stage breast cancer
Authors: A. N. Budrukkar, R. Sarin, R. Jalali, R. Badwe, V. Parmar, M. Nadkarni, D. Deshpande, T. Shet, K. Dinshaw
Journal: Journal of Clinical Oncology (2006)

10661 Purpose: The aim of the study is to evaluate the safety and feasibility of radical brachytherapy for accelerated partial breast irradiation (APBI) and to study the outcome with respect to local control and survival. Materials and Methods: During May 2000 to December 2004, 115 women participated in the ongoing prospective study of APBI using interstitial brachytherapy as the sole modality of radiation for early breast cancer. Women with age &gt; 40 years, single tumour up to 3 cm without diffuse microcalcification and clinically negative axilla were considered suitable. Brachytherapy was done either intraoperatively during the breast conserving surgery or postoperatively using 2–4 planes. Tumor bed demarcation was done with radiopaque clips placed during surgery, CT scans, ultrasonography and/or fluoroscopy. Cavity with 1cm margin was treated based on orthogonal pair of X rays to a dose of 34 Gy in 10 fractions over 1 week with twice daily fractionation using high dose rate iridium source. Results: Implant was done postoperatively in 35 patients while in remaining patients it was done intraoperatively. Implant procedure was tolerated well by all the patients. In 8 patients only 3 or 4 fractions of HDR Brachytherapy were delivered and this was followed by 45 Gy/25 # whole breast radiation therapy for following reasons: positive nodes (4), EIC positive (3) and poor implant coverage (1). At a median follow up of 23 months, the actuarial local control rate is 100%. Three year actuarial disease free survival is 93% while the overall survival is 100%. Complications included fat necrosis in 5 and wound gape in 4 patients. Cosmesis was good to excellent in 60% of the patients. Conclusion: In this ongoing prospective study, APBI using radical interstitial implant was well tolerated and appears to be safe and feasible in appropriately selected patients. Further follow up is needed for confirm the long term safety of the procedure. No significant financial relationships to disclose.