tbuckley/cabot-search huggingface dataset:
Biosimilars: Approval and Acceptance?
Authors: Jessica K. DeMartino
Journal: Journal of the National Comprehensive Cancer Network (2011)

Obama signed into law the Patient Protection and Affordable Care Act.The Affordable Care Act contains a subtitle "Biologics Price Competition and Innovation Act of 2009" (BPCI Act) with information that establishes an abbreviated approval pathway for biologic products that are shown to be "highly similar" to or "interchangeable" with an FDA-licensed biological product.A biologic agent is a product derived from living sources, such as viruses, bacteria, or human and other animal sources.General classes of biologic agents include monoclonal antibodies, complex sugars, blood derivatives, vaccines, and recombinant or purified proteins such as cytokines, thrombolytic agents, and enzymes.The objectives of the BPCI Act are conceptually similar to those of the Drug Price Competition and Patent Term Restoration Act of 1984 (commonly referred to as the Hatch-Waxman Act), which established abbreviated pathways for the approval of drug products (i.e., "generics") under the Federal Food, Drug, and Cosmetic Act (FD&C Act).The BPCI Act aligns with the FDA's longstanding policy of permitting appropriate reliance on what is already known about a drug, thereby saving time and resources and avoiding unnecessary duplication of human or animal testing.However, biologic agents can present challenges to implementing an abbreviated approval pathway for many reasons.First, biologics are considerably more complex than most chemical entities due to increased molecular weight, complicated and patented manufacturing processes, immunogenicity issues, and analytical issues related to determining properties unique to these agents.Second, the clinical consequences of subtle differences in biosimilar products may vary; therefore, assessment on an individual product basis is warranted.
Abstract 14844: An in vitro Model of Early- and No-Reperfusion-Scars to Understand Differences in Reentrant Arrhythmia Characteristics and Potential Therapeutic Interventions
Authors: Said Askar, Sebastiaan Piers, Katja Zeppenfeld, Martin Schalij, Daniel Pijnappels
Journal: Circulation (2012)

Purpose: Early-reperfusion therapy for myocardial infarction (MI) causes patchy scars, whereas no reperfusion causes compact scars. Patchy scars show lower inducibility and shorter cycle length of ...
MR-sialography as functional separate imaging of salivary gland for evaluation of radiation-induced xerostomia
Authors: M. Yokokawa, N. Uchida, A. Wada, A. Kawaguchi, M. Notani, H. Kitagaki, K. Uchida, S. Hara
Journal: Journal of Clinical Oncology (2007)

16522 Background: For head and neck cancer (HNC) patients who receive curative irradiation (RT), RT-induced xerostomia is a frequent and troublesome adverse event diminishing quality of life. In this prospectve study, morphological changes in salivary glands were evaluated by means of MR volume calculation and examination of the functional changes in MR-sialography as compared with subjective symptoms. Materials and Methods: Sixteen HNC patients (15 squamous cell carcinomas and 1 lymphoma) scheduled to receive more than 44 Gy to the primary tumor were registered (median dose to salivary glands: 60 Gy). MRI was performed prior to start of RT (pre-RT), as well as 2–4 weeks after completion of RT (post-RT). Evaluations were undertaken as follows: 1) Subjective symptoms of oral dry sensation were scaled by visual analogue scale (pre-RT VAS, post-RT VAS); 2) Changes in depictions of MR-sialography (heavy T2WI) following tartaric acid stimulation were graded into three categories (good,fair, poor); and, 3) Changes in salivary gland volume were measured as reduction ratio(%) = (pre-RT volume - post -RT volume) / pre-RT volume × 100. Results: Post-RT VAS of oral dry sensation was greater than that of pre-RT (p=0.001). Clinical symptoms (changes in VAS) did not correlate with salivary gland reduction ratio nor radiation dosage for either the parotid (PG) or submandibular glands (SG). RT dosage and reduction ratio correlated well (r=0.62). Reactivity of MR-sialography stimulated by tartaric acid became poor after RT. The mean RT dosages to PG and SG of the poor group were higher than those of the good group (p&lt;0.05). Conclusions: MR-sialography after RT showed a poor response to secretion stimulation, which correlated with RT dosage. Moreover, MR- sialography with secretion stimulation may have the potential to be a non-invasive and sensitive method by which to assess the severity of xerostomia of each gland separately as ‘functional MR - sialography‘. More cases and longer follow up, and dose-volume histogram evaluation of each salivary gland are required to confirm the results. No significant financial relationships to disclose.
Clinical and pathological features of breast cancer in Arab compared to Jewish women in Northern Israel
Authors: J. Zidan, M. Geslikov
Journal: Journal of Clinical Oncology (2009)

e22201 Background: Breast cancer (BC) is the most common malignancy in both Jewish and Arab women in Israel. Although the incidence of BC is lower in Arab women it is diagnosed in younger age and seems to have worse prognosis. Recent data have suggested considerable molecular differences in BC from various ethnical groups. Molecular features are increasingly used for predicting cancer prognosis and response to treatment. The purpose of this study to compare clinical, pathological and molecular characteristics of BC in Arab and Jewish women in the Upper Galilee Methods: The files of 481 patients (pts) with breast cancer (BC) treated at the Oncology Institute, Ziv Medical Center between 2001 and 2007 were reviewed retrospectively. Type of breast operation and both clinical and all pathological findings of patients were summarized and correlated to the ethnicity of women. Results: Of the total 481 pts 380 were Jewish and 100 were Arab women. The main age at diagnosis was 49,4 years for Arabs and 59,5 years for Jews (p&lt;0,01). At diagnosis 3% of Arab pts had DCIS compared to 7,4% in Jewish pts, stage I in 19% and 49,9%, stage II in 36% and 31,7%, stage III in 33,3% and 7,6%, stage IV in 9% and 3,7% of Arab and Jewish pts respectively (p&lt;0,05). Well differentiated, moderately and poorly differentiated in 12%, 59% and 29% compared with 43,9%, 41,4% and 12,5% in Arabs versus Jews. Estrogen receptor was 69% in Arabs and 79% in Jews. HER-2 overexpression evaluated by IHC and CISH was diagnosed in 39% of Arab pts and in 24% Jewish pts (p&lt;0,05). Lumpectomy was done in 36% in Arabs versus 64% in Jews (p&lt;0,05). Conclusions: Our data demonstrate younger age and more advanced tumor at diagnosis in Arab compared to Jewish women. All pathological and molecular figures were more aggressive in Arab compared to Jewish women in Israel. Mammography for screening may be started at age 40 years in Arab women and treatment could be more aggressive. No significant financial relationships to disclose.
Coping with cancer: Associations between coping methods and use of intensive life-prolonging care near death
Authors: A. C. Phelps, P. K. Maciejewski, M. Nilsson, T. A. Balboni, A. A. Wright, E. Trice, S. D. Block, H. G. Prigerson
Journal: Journal of Clinical Oncology (2009)

9575 Background: Cancer patients cope with advanced illness in a variety of ways, including relying on their religious beliefs. Religious coping has been associated with preference for aggressive care near death, yet little is known about how religious and other coping mechanisms effect the use of intensive life-prolonging care at the end-of-life (EOL). We sought to determine how patient coping mechanisms affect the use of intensive life-prolonging EOL care among advanced cancer patients. Methods: The Coping with Cancer Study is a US multi-site, prospective, longitudinal cohort of 345 advanced cancer patients enrolled January, 2003 -August, 2007. The Brief COPE assessed active coping (e.g., problem solving), emotional-support based coping (e.g., getting comfort from others), and behavioral disengagement (e.g., giving up the attempt to cope). The Brief RCOPE assessed positive religious coping (e.g., seeking a strength and guidance from God) and negative religious coping (e.g., believing illness is God's punishment). Patients were followed until death, a median of 122 days after baseline assessment. The main outcome was receipt of intensive life-prolonging care, defined as receipt of ventilation or resuscitation in the last week of life. Results: Greater use of positive religious coping prospectively predicted receipt of intensive life-prolonging care (AOR, 5.43; p&lt;0.001), ventilation (AOR, 4.40; p&lt;0.01), resuscitation (AOR, 5.19; p&lt;0.05), and death in the intensive care unit (AOR, 2.76; p&lt;0.05) in the last week of life, controlling for confounding factors and other examined coping styles. In analyses that adjusted for significant confounding influences, behavioral disengagement was associated with DNR order completion (AOR, 2.80; p&lt;0.01), and prospectively predicted lower rates of intensive life-prolonging care (AOR, 0.20; p&lt;0.05), and ventilation (AOR 0.13, p&lt;0.05). Conclusions: The manner in which patients cope with advanced cancer predicts receipt of intensive life-prolonging care at the EOL. Specifically, positive religious coping predicts the receipt of aggressive medical care near death. No significant financial relationships to disclose.
Phase II trial of neoadjuvant chemotherapy (NCT) with weekly nanoparticle albumin-bound paclitaxel (Nab-P), carboplatin (CBP), and bevacizumab (BEV) in women with clinical stages II-III breast cancer (BC): Pathologic response prediction by changes in angiogenic volume (AV) by dynamic contrast magnetic resonance imaging (DCE-MRI).
Authors: E. Mrozek, M. B. Lustberg, M. V. Knopp, D. G. Spigos, X. Yang, L. A. Houton, B. Ramaswamy, R. M. Layman, S. P. Povoski, D. M. Agnese
Journal: Journal of Clinical Oncology (2010)

604 Background: BEV in combination with paclitaxel improves the outcome of previously untreated metastatic BC patients (Miller et al NEJM 357, 2007). We hypothesized that adding BEV to weekly Nab-P and CBP as NCT would be well tolerated, have improved anti-tumor activity and early changes in AV by DCE-MRI would correlate with pathologic response. Methods: Pts with clinical stages II/III and HER2-non- overexpressing BC received Nab-P 100 mg/m2 IV and CBP AUC=2 IV on days 1, 8, and 15 in combination with BEV 10 mg/kg on days 1 and 15 administered every 28 days for 5 cycles; in the sixth cycle BEV was omitted. DCE-MRI was performed pre NCT, after 2 cycles and prior to the definitive surgery. Pathologic complete response (pCR) was defined as absence of invasive tumor in breast and axilla. Results: Thirty of planned 33 pts were enrolled. The median age was 48 years; 21 (70%) pts were premenopausal; 19 (63%) pts had ER/PR positive BC and 11 (37%) had triple negative BC (TNBC). Treatment was well tolerated with exception of grade 3 and 4 neutropenia in 14 (48%) and 2 (7%) and thrombocytopenia in 2 (7%) and 1 (3%) respectively. Thus far, 17 pts finished NCT; 12 (71%) received all 6 cycles with remaining 5 (29%) pts received < 3 cycles of NCT. The primary reason for not completing all 6 cycles was myelosuppression (n = 4) and disease progression (n = 1). Fourteen pts had definitive surgery: 6 (43%) had lumpectomy, and 8 (57%) had mastectomy. Three (21%) pts had pCR and 3 (21%) had microscopic residual disease (MRD). In the TNBC group the pCR rate was 50% (3 out of 6 pts). At the end of cycle 2, the relative AV decreased from 73% ± 10% in baseline DCE-MRI to 38% ± 37% in pts with pCR and MRD. The relative AV increased from 68% ± 25% in baseline DCE-MRI to 87% ± 18% in non-responders. The changes in relative AV were significantly different between responders and non-responders (p = 0.016). Conclusions: The combination was more myelosuppressive than expected. Early change in relative AV by DCE-MRI may predict response to NCT. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abraxis BioScience, Roche
German drug companies are criticised for not focusing on useful therapeutic areas
Authors: Ned Stafford
Journal: BMJ (2015)

A 2011 German law designed to lower prices of new innovative drugs has not been as successful as envisioned, as drug firms continue to focus efforts on marketing expensive new drugs with little or no added benefit compared with drugs already on the market, says the Innovation Report 2015 ,1 an annual study commissioned by Techniker Krankenkasse, Germany’s largest public health insurer.

Of the 20 new drugs introduced in 2012 and subsequently monitored during 2013 the only drug to receive the highest rating for showing “innovative therapeutic advances” was the cancer growth blocker vemurafenib, a treatment for melanoma. Of the remaining 19 drugs introduced in 2012 seven were rated …
Risk perception in genetic counselling for hereditary breast/ovarian cancer
Authors: A. Savarese, C. Vigna, F. M. Sega, B. Marozzo, I. Sperduti, F. Cognetti, A. Caruso
Journal: Journal of Clinical Oncology (2008)

1541 Background: The estimation of the objective risk (OR) to develop a tumour is a crucial element of genetic counselling. The estimation of the subjective risk (SR) is also important because it affects the patients distress level and influences their adhesion to clinical management. This study evaluates the perception levels of the risk to be a mutation carrier and to develop a related-cancer, the association between perceived risk and medical / psychological variables and the adequacy of the perceived risk compared to the objective risk estimated by BRCApro model. Methods: Before collecting family pedigree, the patients were informed about the clinical involvement of BRCA1/BRCA2 genes mutation, and then about their eligibility to genetic testing and objective risk as estimated by BRCApro model. At this time, questionnaires for evaluation of medical-demographic characteristics, Cancer and Genetic Risk Perception (CRP, GRP) and Hospital Anxiety Depression scale were administered. Statistical analysis was performed by Pearson chi-square test, t-test, Cohen's coeff. of agreement and non parametric test. Results: 130 subject were evaluated: women/men=119/11, 32% affected, 68% healthy with at least two cancer affected-relative. Overall, subjects entering into genetic counselling had higher anxiety level (median score >13) than normal population (< 13) and overestimated their genetic (67%) and tumor risk (56%). The SR was found to be correlated to OR as assessed by BRCApro (CRP r=0.254 p=0.006; GRP r=0.322 p<0.000) but the OR is significantly lower than the SR (CRP=39% vs19%, p<0.001; GRP=31% vs 11%, p<0.001). Subjects eligible for genetic testing showed a higher perception of risk when compared to non-eligible (CRP p=0.024; GRP p<0.001) even if this estimate was more in accordance with BRCApro model than in non eligible (CRP p=0.001; GRP p=0.006). The subjects with less cancer-affected relatives significantly overestimated their risk of being mutation carrier (p=0.028). No association was found between other medical-demographic variables. Conclusions: Subjective and objective risk were found to be correlated. However, a high percentage of subjects overestimate their risk. Only the eligible status and the number of cancer affected relatives seem to influence the perceived risk. No significant financial relationships to disclose.
[18]F-NaF - A Specific Marker for Vascular Calcification in Atherosclerosis
Authors: Agnese Irkle, Joseph L. Bird, Jeremy N. Skepper, Marc R. Dweck, Francis R. Joshi, Alex T. Vesey, Martin Bennett, David E. Newby, Elizabeth A. Warburton, James H. Rudd, Anthony P. Davenport
Journal: Circulation (2013)
Short- and long-term genitourinary symptom status and global quality of life (QOL) from a Southwest Oncology Group (SWOG) Trial
Authors: K. A. Hayden, C. M. Moinpour, J. Faulkner, C. M. Tangen, E. D. Canby-Hagino, D. Lemmon, S. Breslin, I. M. Thompson, E. D. Crawford
Journal: Journal of Clinical Oncology (2005)

4556 Background: This trial compared the impact of radical prostatectomy alone (RP) versus radical prostatectomy plus adjuvant radiation therapy (RPRT) on clinical outcomes and QOL; this abstract reports symptom and global QOL results. Methods: 219 of the 431 therapeutic trial patients were registered to the QOL study (108, RP arm; 111, RPRT arm). Patients completed the SWOG Quality of Life Questionnaire (physical, role, social, and emotional function as well as general symptom status and treatment/disease-specific symptoms and side effects) at baseline, 6 weeks, 6 months, and annually for five years: bowel function (tenderness/urgency); frequent urination; erectile dysfunction, and unpleasant global QOL. All symptoms were classified as bothersome if rated negatively on a 4 or 5-point scale (≥3); global QOL was classified as unpleasant (<5) if not rated as normal (5) on a 5-point scale. Comparisons by arm were made for each outcome using a test for proportions. The level of significance was adjusted for multiple comparisons (<.0125). Conclusions: Men receiving RP + RT reported significantly more tenderness/urgency with bowel movements, more frequent urination, and unpleasant global QOL early on during the trial. However, all significant treatment arm differences had disappeared by 5 years. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Southwest Oncology Group
DNA methylation array analyses to identify<i> HYAL2</i> methylation in peripheral blood as a marker for the detection of early breast cancer.
Authors: Rongxi Yang, Katrin Pfuetze, Manuela Zucknick, Christian Sutter, Frederik Marme, Andreas Schneeweiss, Rita K. Schmutzler, Claus Bartram, Barbara Burwinkel
Journal: Journal of Clinical Oncology (2014)

26 Background: Early detection is crucial to improve the survival rate and quality of life of breast cancer (BC) patients. Changes in DNA methylation in peripheral blood could be associated with malignancy at early stage. We aim to identify BC-associated DNA methylation signatures in peripheral blood. Methods: We identified a BC-associated differentially methylated locus by genome-wide investigation using Illumina 27K Methylation Assay. Two validation studies and replications in leucocytes and T cells were carried out using MassARRAY. The RNA expression levels were measured by real-time PCR. Results: The methylation level of CpG site cg27091787 in hyaluronoglucosaminidase 2 gene (HYAL2) in peripheral blood was significantly lower in BC cases than in controls (discovery round, 72 BC case and 24 controls, p = 2.61 × 10 -9 adjusted for cell-type proportions; first validation round,338 BC case and 507 controls, p &lt; 0.0001; second validation round,189 BC case and 189 controls, p &lt; 0.0001). Compared to the highest quartile, the lowest quartile of cg27091787 methylation was associated with a more than 40-fold increased risk of BC (p &lt; 0.0001). In addition to cg27091787, the decreased methylation of a 650 bp CpG island shore of HYAL2 was also associated with BC. Moreover, the expression and methylation of HYAL2 in leucocytes were inversely correlated (p = 0.006). To note, the BC-associated decreased HYAL2 methylation was replicated in T cell fraction (p = 0.034). The cg27091787 methylation level enabled a powerful discrimination of early stage BC cases from healthy controls (area under curve (AUC) = 0.88), and was also robust for the detection of BC in younger women (AUC = 0.87). Conclusions: Validating the epigenome-wide study by independent cohorts, we have revealed a strong association between decreased HYAL2 methylation in peripheral blood and BC. Our results have given an answer to the debate on the origin of BC-associated differential methylation in blood, which is not only because of the change of cell type proportions, but more importantly due to altered methylation in specific blood cell fragments, like in T cells. And thus, we provide a promising blood-based marker for the detection of early BC.
Pattern of palliative care, pain management, and referral trends in developing countries: Still far from optimum
Authors: K. Sharma, B. K. Mohanti, D. N. Sharma, G. K. Rath, P. K. Julka, S. Muzumder
Journal: Journal of Clinical Oncology (2009)

e20694 Background: Although palliative care and pain management are essential components of oncology practice, studies show that these areas are often inadequately addressed, more so in the developing countries where palliative care and pain management units are still inadequate. Methods: We randomly selected 252 patients receiving palliative RT (radiotherapy) at our tertiary care centre for oncology, from October 2006 to august 2008. Patients with bone pain were excluded as it could add a bias. Patient's records were studied retrospectively. Results: A median follow-up of 21 weeks was available for 197 males and 55 females with a median age of 55 years. Maximum (60%) patients were of head and neck cancers followed by oesophagus (14%), lung (10%) and others. All cases belonged to stage III (27%) or IV (73%). Dysphagia (35%), growth/ulcer (34%), respiratory symptoms (12.5%) and pain (7%) were the chief indications for palliative treatment. Overall, pain was present in 154 (61%) cases, out of which 92 (60%) were referred to pain clinic. All except two consulted pain clinic with a median pain score of 8 (0–10 point scale). Eighty six (96%) patients received opioid based treatment with adequate pain relief in 33% cases and loss of follow-up in 40% cases. Only eight (3%) cases were referred to a hospice. Thirty six (14%) cases were considered for radical treatment following very good response to palliative RT. Conclusions: In this selective sample, the standard of analgesic treatment is satisfactory. However, there is a lot of scope for improvement regarding referral to pain clinic and later to the hospice. Patients’ follow-up needs to be improved along with further studies evaluating patients who are considered for further RT till radical dose. Programs to change the patients’ attitude towards palliative care, physicians’ (residents) training to improve communication skills, and institutional policies may be the promising strategies. No significant financial relationships to disclose.