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Background: Studies of immune checkpoint inhibitors combined with chemotherapy show activity in metastatic breast cancer (MBC). There is no data regarding sequencing of pembrolizumab (pem) in relation to chemotherapy in MBC patients (pts). We investigated the safety of a phased schedule vs concurrent schedule of paclitaxel (pac) and pembrolizumab (pem). Methods: Eligible pts had HR+HER2-negative or triple-negative (TN) MBC, ≥2 lines of hormone therapies and 0-3 prior lines of chemotherapy for MBC. Pts were randomized 1:1 to 2 cycles of pac 80 mg/m2 IV on D1 and D8 followed by pac and pem 200 mg/m2 IV on D1 of a 21-day cycle (Arm A; phased schedule) or pac and pem given together starting D1 of a 21-day cycle (Arm B; concurrent) and continuing until progression or toxicity. Primary objective was to continuously monitor overall grade 3 or 4 treatment-related adverse event (TRAE) rate for each arm and compare to relevant historical controls with Bayesian stopping rules. If the grade 3 or 4 TRAE rate convincingly exceeded 0.35 on either arm, enrollment to that arm would be halted. Secondary objectives were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Exploratory analyses assessed PD-L1 and tumor infiltrating lymphocytes (TILs) in the tumor and blood markers immunotyping. Results: Forty female pts were randomized (21 in Arm A and 19 in Arm B). Median age was 40 (range 28-76). Twenty pts were HR+HER2-negative; 20 pts had TNBC; 7 pts had de novo MBC. Median prior lines of chemotherapy was 1 (range 0 - 3); median no. of cycles was 7 (1-27); 7 pts in Arm A did not initiate pembrolizumab due to disease progression. The criteria for stopping enrollment based on Bayesian stopping rules were not met for either arm; 24% of subjects (5 of 21) on Arm A and 32% (6 of 19) on Arm B experienced stopping rule events. At the data cut-off of 2/16/21, with median follow-up of 10.1 months, overall ORR was 30% with 12 partial responses, and ORR in HR+HER2-negative and TNBC were 30% and 30%, respectively. Grade 3-4 TRAE rates were 24% in Arm A and 32% in Arm B. The most common grade 3-4 TRAES were peripheral sensory neuropathy (2 pts [10%] in Arm A; 3 pts [16%] in Arm B), decreased neutrophil count (1 pt [5%] in each Arm), and anemia (1 pt [5%] in each Arm). In the overall group, immune-related adverse events (irAEs) occurred in 28% of pts; 5% of these events were ≥ grade 3 in Arm A (gr 3 AST/ALT increased in 1 pt) and 5% in Arm B (gr 3 lipase increased in 1 pt). The most common irAE was hypothyroidism (6 pts, 15%). Tumor PD-L1 assay and TILs were performed in 39 pts and blood immunotyping on all pts. Seven pts (18%) had PD-L1 positive tumors (PDL-1 H-score ≥ 5, centrally tested) and 19 (48.7%) had significant immune infiltration (TILs score 2-3). Biomarker analysis is currently in progress. Updated data, including ORR, PFS and OS by arm, is expected to be presented. Conclusions: Both the phased and concurrent schedules of pac and pem were found to be safe and feasible. The combination’s safety profile was consistent with the known individual agent’s safety profile. Clinical activity was demonstrated in both metastatic HR+HER2-negative and TNBC pts. Clinical trial information: NCT03018080. Citation Format: Antoinette R. Tan, S. Jean Chai, Myra M. Robinson, Lane B. Hellner, Nagajyothi Gavini, Nanna Sulai, J. David Turner, Jennifer Atlas, David L. Graham, Raghava R. Induru, Kunal C. Kadakia, Geetha D. Vallabhaneni, Arielle L. Heeke, David M. Foureau, Julie G. Fisher. A pilot study of paclitaxel plus pembrolizumab in patients with metastatic HER2-negative breast cancer (PePPy) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-14-03.

A MESSAGE FROM ASCO’S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors’ genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients’ own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy—a type of adoptive cell immunotherapy—has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation’s support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal research investment to accelerate the discovery of the next generation of cancer treatments. Another major trend in this year’s report is progress in precision medicine approaches to treat cancer. Although precision medicine offers promise to people with cancer and their families, that promise is only as good as our ability to make these treatments available to all patients. My presidential theme, “Delivering Discoveries: Expanding the Reach of Precision Medicine,” focuses on tackling this formidable challenge so that new targeted therapies are accessible to anyone who faces a cancer diagnosis. By improving access to high-quality care, harnessing big data on patient outcomes from across the globe, and pursuing innovative clinical trials, I am optimistic that we will speed the delivery of these most promising treatments to more patients. Sincerely, Bruce E. Johnson, FASCO ASCO President, 2017 to 2018

Purpose Ovarian cancer is the most fatal of all gynecologic cancers, with a high relapse rate regardless of stage. Women treated for ovarian cancer, therefore, likely have supportive care needs that extend well beyond the time frame of first-line therapy. Unfortunately, there is minimal data describing these needs. The purpose of this qualitative study is to understand the supportive care needs of women with ovarian care at the end of treatment. Methods To better understand the issues faced by women with ovarian cancer, we conducted a public Twitter chat in collaboration with gynecologic cancer social media (#gyncsm). Both quantitative and qualitative analyses were performed. Results The chat occurred over a 1-hour time frame on Twitter and resulted in more than 300 unique and original tweets from 43 participants during the chat and an additional 60 unique participants following the chat. Survivors and physicians represented 32% and 11% of participants, respectively; caregivers, advocates, and other clinicians represented the remaining participants. Participants noted deep interest in receiving support during survivorship and dissatisfaction with currently available resources. Sentiment analysis showed that participants viewed the support from social media in a positive light and also revealed negative sentiment around the lack of support from health care providers at the end of treatment. Conclusions Themes derived from the Twitter chat revealed the unique experiences of individuals with ovarian cancer after treatment, including a heightened sense of vulnerability. Understanding these themes represents an opportunity for clinicians to better understand and address the needs of this patient community.

Twitter use by physicians, including those in the hematology – oncology field, is increasing. This microblogging platform provides a means to communicate and collaborate on a global scale. For the oncology professional, an active Twitter presence provides opportunities for continuing medical education, patient engagement and education, personal branding, and reputation management. However, because Twitter is an open, public forum, potential risks such as patient privacy violations, personal information disclosures, professionalism lapses, and time management need to be considered and managed. The authors have summarized the benefits and risks of Twitter use by the hematology – oncology physician. In addition, strategies to maximize benefit and minimize risk are discussed, and resources for additional learning are provided.

Social media has become an established method of communication, and many physicians are finding these interactive tools and platforms to be useful for both personal and professional use. Risks of social media, or barriers to its use, include perceived lack of time, privacy concerns, and the risk of damage to one’s reputation by unprofessional behavior. Of the social media platforms, Twitter has become favored by physicians and other health care professionals. Although one of the most obvious uses of social media is for rapid dissemination and receipt of information, oncologists are finding that social media is important for networking through blogs, Facebook, and Twitter. These platforms also have potential for providing opportunities for professional development, such as finding collaborators through networking, participation in Twitter journal clubs, and participating in online case-based tumor boards. Social media can also be used for patient engagement, such as through participation in tweet chats. There is emerging data that patient engagement through these platforms may lead to improvement in some health-related outcomes; however, data are sparse for oncology-specific outcomes. Efforts are underway to determine how to assess how social media engagement impacts health outcomes in oncology patients.

1531 Background: Vaccines are a major step towards control of the COVID-19 pandemic. Estimates from multiple surveys of the general public indicate that 40 to 60% plan to be vaccinated, with some data suggesting that uptake differs by political leanings. The views of people with cancer on COVID-19 vaccination have not been reported. We report survey results of people with cancer, evaluating intent and attitudes toward COVID-19 vaccinations. Methods: An online survey included self-identified patients with cancer, ≥18 years old, in the Inspire Online Community (www.inspire.com). Invitation was restricted to only members of Inspire’s cancer support groups who agreed to be contacted for research. Quantitative data were summarized with descriptive statistics. Data were analyzed by chi-square, ANOVA, and post hoc Tamhane’ T2 testing. Results: 750 responded with the most common cancers represented being prostate (30%), thyroid (24%) ovarian (20%), bladder (8%) and breast (4%). 44% were between 46 and 65 years old and 48% were over 65. Of these, 38% reported being on active treatment. The majority were white (91%), female (56%) and had a bachelor’s degree or higher (72%). Respondents represented the South (38%), West (28%), Midwest (20%), and Northeast (18%). Nearly half of respondents lived in a suburb near a large city. Almost 40% reported an annual income of > $100,000 and 13% reported income < $50,000/year. The proportion that would “definitely” or “most probably” get the COVID-19 vaccine was 80%, with significantly greater interest in people with prostate (85%), bladder (82%) and ovarian cancer (81%). Those with breast cancer reported the highest levels of being uncertain (23%) and 30% of those with thyroid cancer reported they would “probably” or “definitely” not get vaccinated. Older age, male sex, and college graduates were significantly more likely to get vaccinated. Concerns about side effects were reported by 54%, with younger patients significantly more concerned than those 66 years and older. Of 158 participants who listed other reasons they would not get vaccinated, 23% were concerned that the research and development was rushed and 11% worried about how it might interact with a compromised immune system. Using the 2020 Electoral College map to indicate political leaning at the state level, there was no significant difference in vaccine uptake, although significantly more people from blue states agreed that vaccination was the best defense against COVID-19 compared to those from red states (67 vs 33%, p

Purpose To provide recommendations for the management options for patients with small renal masses (SRMs). Methods By using a literature search and prospectively defined study selection, we sought systematic reviews, meta-analyses, randomized clinical trials, prospective comparative observational studies, and retrospective studies published from 2000 through 2015. Outcomes included recurrence-free survival, disease-specific survival, and overall survival. Results Eighty-three studies, including 20 systematic reviews and 63 primary studies, met the eligibility criteria and form the evidentiary basis for the guideline recommendations. Recommendations On the basis of tumor-specific findings and competing risks of mortality, all patients with an SRM should be considered for a biopsy when the results may alter management. Active surveillance should be an initial management option for patients who have significant comorbidities and limited life expectancy. Partial nephrectomy (PN) for SRMs is the standard treatment that should be offered to all patients for whom an intervention is indicated and who possess a tumor that is amenable to this approach. Percutaneous thermal ablation should be considered an option if complete ablation can reliably be achieved. Radical nephrectomy for SRMs should only be reserved for patients who possess a tumor of significant complexity that is not amenable to PN or for whom PN may result in unacceptable morbidity even when performed at centers with expertise. Referral to a nephrologist should be considered if chronic kidney disease (estimated glomerular filtration rate < 45 mL/min/1.73 m2) or progressive chronic kidney disease occurs after treatment, especially if associated with proteinuria.

10.2217/fon-2016-0065 © 2016 Future Medicine Ltd Social media is transforming cancer communication Social media, defined as online functions that enable users to create, share, comment upon or modify content, is rapidly changing the way patients with cancer obtain health information [1]. When one looks at the use of social media, nearly two-thirds of American adults (65%) were online in 2015, up from 7% in 2005 [2]. Use of social media extends to cancer care, and patients and their families are increasingly using various forms of social networking (e.g., Twitter, Facebook, blogs) to interact with each other and with oncology professionals, form communities and receive and obtain credible information about their health or that of their loved ones [3]. Social media technologies can serve as key health communication channels, granting clinicians and the public alike unprecedented access to conversations touching on topics such as cancer prevention, treatments and research. However, while social media is a powerful tool to convey health information, it also imposes multiple challenges, including the difficulty in assessing the reliability of sources, lack of privacy and confidentiality, the potential for inaccurate medical advice, propagation of negative health behaviors and information overload. The purpose of this article is to highlight three ways that social media may be effectively used in cancer care: enhancing the patient–provider relationship, connecting COMMENTARY

The penetration of social media into modern society has become a worldwide cultural phenomenon. Social media use widely accessible Web-based and mobile technologies to facilitate the creation and sharing of user-generated content in a collaborative and social manner. The uptake of social media in medicine provides new opportunities for health care professionals and institutions to interact with patients and other professionals. Oncologists may use social media as a platform for patient education and authoritative health messaging, for professional development and knowledge sharing, and for direct patient interaction, although this may be fraught with important legal and privacy concerns. In this article, a working group of the ASCO Integrated Media and Technology Committee explores how oncologists might responsibly use social media in their professional lives. Existing social media policies from hospitals, health systems, and pharmaceutical industries are examined to identify common concepts informing the development of future guidelines. Key principles identified include establishing institutional ownership of social media activities and safeguarding protected health information. Furthermore, oncologists must not confuse the roles of provider of information and provider of care, must understand regulations related to state licensure and medical records, and must recognize the importance of transparency and disclosure of potential conflicts of interest. social media may be particularly useful for raising the awareness of and recruitment to clinical trials, but compliance with federal and state regulations and areas under the purview of a local institutional review board must also be ensured. Examples of constructive use of social media in oncology with Facebook, Twitter, and YouTube are provided.

This study was conducted to investigate the effect of Se supplementation on prostate cancer incidence in men at high risk for prostate cancer.A Phase 3 randomized, double-blind, placebo-controlled clinical trial was conducted in 699 men at high risk for prostate cancer (prostate specific antigen (PSA)4 ng/ml and/or suspicious digital rectal examination and/or PSA velocity0.75 ng/ml/year), but with a negative prostate biopsy. Participants were randomized to receive daily oral placebo (N = 232), 200 µg selenium (N = 234), or 400 µg selenium (N = 233) as selenized yeast. They were followed every 6 months for up to 5 years. The time to diagnosis of prostate cancer was compared between treatment groups using the Cox proportional hazards model.Compared to placebo, the hazard ratios [95% confidence intervals] for risk of developing prostate cancer in the selenium 200 µg/day or the selenium 400 µg/day group were 0.94 [0.52, 1.7] and 0.90 [0.48, 1.7], respectively. PSA velocity in the selenium arms was not significantly different from that observed in the placebo group (P = 0.18 and P = 0.17, respectively).Selenium supplementation appeared to have no effect on the incidence of prostate cancer in men at high risk. In conjunction with results of other studies, these data indicate that selenium supplementation may not have a role in prostate cancer chemoprevention.

Ewing's sarcoma is the second most common primary sacral tumor. Ewing's sarcomas are rare, aggressive tumors with a tendency towards recurrence following resection and early metastasis. Although peak incidences are between the ages of 10 and 20 years, patients of younger or older age account for almost 30% of the cases. We report the case of a 52-year-old healthy female who presented with a 2-week history of pain in her right posterior thigh that was unable to be relieved by non‑steroidal anti‑inflammatory medicine and physical therapy. Magnetic resonance imaging demonstrated an irregular right presacral mass and core needle biopsy revealed a small, round blue cell neoplasm. Staging workup was normal and an open biopsy was positive for the ES translocation (22q12). The patient was treated with 17 cycles of vincristine, adriamycin and cytoxan with mesna rescue, alternating with ifosfamide and etoposide in addition to external beam radia- tion. Post-treatment imaging demonstrated complete resolution of the tumor. Six weeks post-treatment the patient presented with a recurrent tumor. This case emphasizes the importance of timely establishment of initial diagnosis, early metastasis in treatment responsive patients and under-utilization of posi- tron emission tomography-computed tomography (PET-CT) during the treatment to detect sub-clinical metastasis.

Background: Docetaxel (T; Taxotere) with capecitabine (X) is active against metastatic breast cancer (MBC); bevacizumab (BV) has demonstrated efficacy with taxanes in the first-line setting. This study was conducted to assess the safety and efficacy of TX-BV in patients with MBC. Patients and methods: In this single-arm, multicenter phase II study, patients received first-line bevacizumab 15 mg/kg and docetaxel 75 mg/m2 on day 1 and capecitabine 825 mg/m2 twice per day on days 1–14 every 21 days. Primary and secondary end points were tumor response rate (RR), overall survival (OS), progression-free survival (PFS), and toxicity. Results: A total of 45 assessable patients received TX-BV for a median of seven cycles. Two complete and 20 partial responses were observed (overall RR 49%); nine patients had stable disease >6 months, for a clinical benefit rate of 69%. Median response duration was 11.8 months. Median OS and PFS were 28.4 and 11.1 months, respectively. Grade 3/4 adverse events included hand–foot syndrome (29%), fatigue (20%), febrile neutropenia (18%), and diarrhea (18%). In cycles 3–10, median dose levels of docetaxel and capecitabine were 60 mg/m2 and 660 mg/m2, respectively. Conclusion: TX-BV demonstrated significant activity; dose modifications were required to manage drug-related toxic effects.

Intercollegiate athletics are a major investment of time for student-athletes who must balance their academic and athletic commitments. For African American males, sports participation may have adverse effects on both their educational outcomes and career development. According to the extant research base, the low academic achievement and high aspirations toward professional athletic careers for many African American males are due to a variety of factors including socialization toward athletics by family, community members, and the media. We posit that African American male student-athletes may prematurely settle on an athletic identity with limited or no exploration to other possible identities, namely career identities. Using an adaptation of Dawkins, Braddock II, and Celaya’s (2009) model of academic engagement, we categorize African American male student-athletes into three persona types; maintenance, incentive, and integrative. Maintenance and incentive persona types value academics as a necessary step toward an athletic career, whereas integrative persona type understands that academics and athletics can benefit a comprehensive career development.

Counseling and Advising Black Male High School Student-Athletes. The Athletic Casting Call: Factors Contributing to the Social Construction of the Black Male College Athlete. Advising Black Male Student-Athletes: Implications for Academic Support Programs. Black Male Academic Support Staff: Navigating the Issues with Black Student-Athletes. Black Male Student-Athletes' Academic and Athletic Experiences at HBCUs. Black Male Student-Athletes on Predominantly White College and University Campuses. Making Sense of Amateurism: Juxtaposing NCAA Rhetoric and Black Male Athlete Realities. The Supply Chain: Discourse on Black Male College Football Players and Revenue Generation. A Cliff (Scholar) and Chris (Baller) Paul State Farm Ad Campaign Analysis. Transformative Black Masculinity: Black Male Student-Athletes and Sexual Violence Prevention. Answering the Call: Black Male Faculty Mentoring Black Male Student-Athletes. Impact of College Athletics Involvement on African American Male Student-Athletes' Career Development. Beyond the GameTM: Transforming Life Outcomes of Black Male Collegiate Student-Athletes. The Legal and Financial Realities of Professional Sports for Black Males. About the Authors. About the Editors. Acknowledgments. Afterword: "Blackness" and "Maleness" in Athletics. Dedication. Foreword. Introduction. List of Contributors. Copyright page. Black Males and Intercollegiate Athletics: An Exploration of Problems and Solutions. Diversity in higher education. Black Males and Intercollegiate Athletics: An Exploration of Problems and Solutions. ENDORSEMENTS.

Purpose: This trial was performed to determine the maximum tolerated dose (MTD) of radiation that can be administered with carboplatin and paclitaxel. Methods and Materials: This trial included 15 patients with unresectable non–small-cell lung cancer. Paclitaxel (50 mg/m 2 ) and carboplatin (area under the curve=2) were given weekly during radiation therapy (RT). The RT included 2 Gy daily to an initial dose of 70 Gy, and the dose was increased in 4 Gy increments until determining the MTD. The MTD was defined as the highest safely tolerated dose where at most 1 patient of 6 experienced dose-limiting toxicity (DLT) with the next higher dose having at least 2 of 6 patients experiencing DLT. Three-dimensional treatment planning techniques were used without prophylactic nodal RT. Results: Two patients were not evaluable because they did not receive therapy according to the protocol. No DLTs occurred in the 3 patients who received 70 Gy, 1 DLT occurred in the 6 patients who received 74 Gy, and 2 DLTs occurred in the 4 patients who received 78 Gy. The DLTs included Grade 3 pneumonitis ( n = 2) and Grade 4 pneumonitis ( n = 1). There have been 3 deaths during follow-up ranging from 14 to 38 months (median, 28 months). Conclusions: The MTD of the RT was 74 Gy with weekly carboplatin and paclitaxel. The Phase II portion of this trial is currently under way. The goal is to improve local control and survival with higher doses of RT delivered with this combined modality approach.

493 Background: Immune checkpoint inhibitors (ICI) targeting PD-1 or PD-L1 are effective in select patients with advanced UC. High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential temporal discordance of tumor PD-L1 expression during the metastatic process. Methods: Immunohistochemical (IHC) staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 83 patients with advanced UC. IHC staining was scored for the percentage of cells positive ( < 5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman’s correlation coefficients (ρ). Cohen’s kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. Results: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.1% and 14.6% of TCs and in 7.8% and 11.7% of ICs. High co-expression of PD-L1 in both TC and IC compartments was infrequent in primary and metastatic lesions (3.6% and 2.6%, respectively). PD-L1 expression in TCs was positively correlated with PD-L1 expression in ICs in primary tumors (ρ = 0.47) and in metastatic lesions (ρ = 0.27). TC PD-L1 expression in primary tumors was correlated with TC PD-L1 expression in paired metastatic lesions (ρ = 0.44) but there was minimal agreement in high expression rates between primary and metastatic lesions in the TC compartment (κ = 0.147). IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ = 0.086). Conclusions: High PD-L1 IC expression is temporally discordant between primary and metastatic UC lesions. Future studies of PD-1/PD-L1 targeted therapies in patients with metastatic UC should utilize recent biopsies of metastatic lesions to define PD-L1 expression when feasible.

Reticuloendotheliosis in captive greater (Tympanuchus cupido pinnatus) and Attwater's (T. cupido attwateri) prairie chickens is reported for the first time. Between September 1993 and August 1994, two adult female wild-caught greater prairie chickens housed at Texas AM University (College Station, Texas, USA) were observed with multiple subcutaneous nodules. Both birds were euthanatized. Complete necropsy examinations revealed lesions limited to the skin of each bird. Histopathologic examination of lesions revealed pleomorphic lymphoreticular cells suggestive of reticuloendotheliosis and reticuloendotheliosis virus (REV) was demonstrated in tumor tissue by polymerase chain reaction and virus isolation. Between September 1994 and June 1995, five additional greater prairie chickens and two Attwater's prairie chickens were euthanatized or found dead with evidence of lymphoreticular neoplasia in multiple organ systems. Initial testing of the captive flock in December 1994 for evidence of viremia and antibody to reticuloendotheliosis virus revealed over 50% of the tested birds were viremic, but none developed antibodies. Subsequent testing between January 1995 and January 1996 indicated that once infected with reticuloendotheliosis virus, Attwater's prairie chickens tended to remain outwardly healthy despite persistent viremia compared to infected greater prairie chickens which had higher morbidity and mortality rates within 60 to 90 days after initial detection of viremia and did not usually develop persistent viremia. Antibodies to REV were detected in only three captive greater prairie chickens and only in 1995. Six of the nine birds that were euthanatized or found dead due to reticuloendotheliosis developed viremia prior to death; three birds were not tested prior to death. Testing of free-ranging greater and Attwater's prairie chickens for reticuloendotheliosis is recommended prior to translocation or release.

Sera collected from wild and captive Australian cockatoos and other psittacine species (n = 411) were tested for antibodies to avian polyomavirus (APV) and Pacheco's disease virus (PDV). Of 144 wild sulphur-crested cockatoos (Cacatua galerita) sampled at three regions in New South Wales (NSW) 96 (64.4%) birds had positive (/= 1:32) neutralizing antibody titres to avian polyomavirus (range 1:32-1:2048). Two of 17 wild long-billed corellas (Cacatua tenuirostris) were also APV-antibody positive. However, no samples from 107 wild galahs (Eolophus roseicapillus) were positive for neutralizing antibody to APV. Sera were also collected from captive psittacine bird flocks from NSW, Tasmania, Victoria, and Western Australia. In a mixed aviary of cockatoos and lorikeets, APV antibody was detected in sera from sulphur-crested cockatoos, Major Mitchell's cockatoos (Cacatua leadbeateri), a white-tailed black cockatoo (Calyptorhynchus baudinii latirostris), a red-tailed black cockatoo (Calyptorhynchus magnificus) a single galah, a rainbow lorikeet (Trichoglossus haematodus), and a scaley-breasted lorikeet (Trichoglossus chlorolepidotus). All 411 wild and captive birds were negative for the presence of neutralizing antibody to PDV. These results indicate that wild sulphur-crested cockatoos in NSW are enzootically infected with avian polyomavirus and that the sampled populations are free of Pacheco's disease.

The black grouse Tetrao tetrix is declining in most of the Alps where it historically occurred. A better knowledge of the genetics of the wild populations and of captivereared birds is necessary for future reintroduction into areas where they historically occurred or where they are endangered. DNA-markers are the choice of method to study genetics of wild populations, but it is difficult to get blood samples from wild birds to extract DNA. A technique based on feathers as the DNA source was developed. DNA extracted from blood and feathers from seven birds was tested by PCR, 80 10-base primers. Only seven primers showed a repeatable amplification profile between DNA sources and polymorphic variation within the population. The selected primers were used to amplify the DNA extracted from wild black grouse feathers in different areas (Trentino, Cuneo, Maritime Alps). The Trentino population presented a reduced genetic variability with an average band sharing (ABS) of 0.76 ± 0.145 in the captive-reared birds vs 0.70 ± 0.17 in all birds. The birds from Cuneo and the Maritime Alps had an ABS of 0.48 ± 0.07 and 0.35 ± 0.10, respectively, and were quite different from the average genotype.

Metastatic carcinoma of unknown primary (CUP) has a very poor prognosis, and no standard first-line therapy currently exists. Here, we report the results of a phase II study utilizing a combination of gemcitabine and irinotecan as first-line therapy. Treatment was with gemcitabine 1000 mg/m2 and irinotecan 75 mg/m2 weekly times four on a six week cycle (Cohort I). Due to excessive toxicity, the dose and schedule were modified as follows: gemcitabine 750 mg/m2 and irinotecan 75 mg/m2 given weekly times three on a four week cycle (Cohort II). The primary endpoint was the confirmed response rate (CR + PR). Secondary endpoints consisted of adverse events based upon the presence or absence of the UDP glucuronosyltransferase 1 family, polypeptide A1*28 (UGT1A1*28) polymorphism, time to progression, and overall survival. Thirty-one patients were enrolled with a median age of 63 (range: 38–94), and 26 patients were evaluable for efficacy. Significant toxicity was observed in Cohort 1, characterized by 50% (7/14) patients experiencing a grade 4+ adverse event, but not in cohort II. The confirmed response rate including patients from both cohorts was 12% (95% CI: 2–30%), which did not meet the criteria for continued enrollment. Overall median survival was 7.2 months (95% CI: 4.0 to 11.6) for the entire cohort but notably longer in cohort II than in cohort I (9.3 months (95% CI: 4.1 to 12.1) versus 4.0 months (95% CI: 2.2 to 15.6)). Gemcitabine and irinotecan is not an active combination when used as first line therapy in patients with metastatic carcinoma of unknown primary. Efforts into developing novel diagnostic and therapeutic approaches remain important for improving the outlook for this heterogeneous group of patients. Trial Registration ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00066781","term_id":"NCT00066781"}}NCT00066781

Population viability analyses for a number of endangered species have incorporated a metapopulation approach. The risk assessments of these viability analyses have indicated that some extant populations should be subdivided into numerous subgroups with exchange of individuals among them in order to reduce the chance of catastrophic loss of the species. However, routine application of a policy of extensive subdivision may have detrimental consequences for certain endangered species. We examine the Puerto Rican Parrot as a case history in which this policy is ill-advised. In 1989, apopulation viability analysis was conducted for the parrot. The document recommended subdivision of the existing small captive flock into three groups. One of these captive flocks would consist of individuals transferred to a multi-species facility in the continental United States. Subsequently, individuals from this facility would be exchanged with the insular captive population(s) and the relict wild flock. For two reasons, implementation of this recommendation might have led to serious repercussions. First, this parrot, like many endangered species, has gone through a genetic bottleneck and may have a heightened susceptibility to disease. Multi-species facilities are a high-risk environment favoring the transmission of pathogens, especially when the facilities are located outside the natural ranges of a particular species. Second, the parrot is a K-selected species for which mate selection is idiosyncratic. This type of species often proves difficult to breed in captivity in small groups. Part of the problem in mate selection may be reduced by a policy allowing frequent transfers of individuals among facilities, but such movements increase the chances of spreading disease in the metapopulation. Thus, population viability analyses need to acknowledge that proliferation of captive subgroups accompanied by exchanges of individuals can in themselves carry substantial risks that must be weighed against the presumed benefits of subdivision. Los analisis de viabilidad de poblaciones hechos para un gran numero de especies en peligro de extincion abora tienen un enfoque de metapoblacion. Para reducir las probabilidades de perdidas catastroficas de individuos de una especie, poblaciones existentes se subdividen en numerosos subgrupos; esto se hace de acuerdo a los resultados de los analisis de riesgo que son parte integral del enfoque de analisis de viabilidad de poblaciones. Sin embargo, la subdivision contiinua y rutinaria de poblaciones de especies en peligro de extincion puede ser detrimental para la sobrevivencia de la especie. Examinamos al caso de la Cotorra Puertorriquena donde este tipo de enfoque no es recomendable. En el 1989, un analisis de viabilidad poblacional se efectuo para la Cotorra Puertorriquena. Como resultado del analisis se recomendo la subdivision en tres grupos de la pequena poblacion cautiva existente. Se recomendo, ademas, transferir uno de los tres grupos a una facilidad con multiples especies en los Estados Unidos de America. Subsiguientemente, individuos de esta facilidad serian intercambiados con las poblaciones cautivas en Puerto Rico y con la poblacion de cotorras aun sobreviviendo bajo condiciones naturales. Hay dos razones por las cuales tales recomendaciones podrian haber repercutido seriamente sobre la cotorra. En primer lugar, esta especie, como muchas otras en peligro de extincion, ha atravesado por un cuello de botella genetico y como resultado de esto su suceptibilidad a enfermedades ha incrementado. Facilidades con multiples especies son ambientes de alto riesgo para especies como la cotorra pues en ellos se favorece la transmision de patogenos, especialmente cuando los facilidades estan localizadas lejos del ambiente natural de especies particulares. En segundo lugar, la cotorra es una especie tipo K para la cual la seleccion de parejas es idiosincratica. Este tipo de especie es generalmente dificil de propagar en cautiverio particularmente cuando las poblaciones son pequenas. Parte del problema de seleccion de parejas se puede aliviar intercambiando frecuentemente individuos entre facilidades, pero tal estrategia aumenta el riesgo de transmision de enfermedades entre las metapoblaciones. Por lo tanto, el analisis de viabilidad de poblaciones debe considerar que la proliferacion de subgrupos cautivos acompanados por el intercambio continuo de individuos en esos subgrupos, por su cuenta, conlleva riesgos sustanciales que se deben contraponer ante los presuntos beneficios de la subdivision de las poblaciones.

Allogeneic bone marrow transplantation (BMT) is a therapeutic modality with a curative potential for chronic granulocytic leukemia. Approximately 20% of patients have a hematologic relapse after BMT. The frequency of cytogenetic or molecular relapse (or both), despite hematologic remission, is reportedly higher. We performed allogeneic BMT in 32 patients with chronic granulocytic leukemia by using unmanipulated donor marrow and a conditioning regimen that consisted of cyclophosphamide and total-body irradiation. Of these 32 patients, 23 had cytogenetic studies after BMT. Seven of these patients had cytogenetically detectable Philadelphia chromosomes some time after BMT, during hematologic remission. The Philadelphia chromosome was detected transiently in two patients, and the fraction of abnormal metaphases exceeded 25% in three patients. None of the patients with negative results of cytogenetic studies or with the presence of the Philadelphia chromosome in less than 25% of analyzed metaphases had a clinical relapse, whereas two of the three patients with more than 25% abnormal metaphases had clinical relapses. Our results suggest that the detection of more than 25% abnormal metaphases during cytogenetic studies for chronic granulocytic leukemia after BMT may imply an incipient clinical relapse. We review the current literature that discusses isolated cytogenetic or molecular relapses of chronic granulocytic leukemia after BMT.

Purpose Hot flashes are a common problem for which effective and safe treatments are needed. The current trial was conducted on the basis of preliminary promising data that pregabalin decreased hot flashes. Patients and Methods A double-blind, placebo-controlled, randomized trial design was used to compare pregabalin at target doses of 75 mg twice daily and 150 mg twice daily with a placebo. Hot flash frequencies and scores (frequency times mean severity) were recorded daily during a baseline week and for six treatment weeks. The primary end point for this study was the change-from-baseline hot flash score during treatment week 6 between the 150 mg twice daily target pregabalin treatment and placebo. Nonparametric Wilcoxon rank sum tests, two-sample t tests, and χ2 tests were used to compare the primary and secondary hot flash efficacy end points between pregabalin treatments and placebo. Results Hot flash score changes available for 163 patients during the sixth treatment week compared with a baseline week decreased by 50%, 65%, and 71% in the placebo, and target 75 mg twice daily and 150 mg twice daily pregabalin arms, respectively (P = .009 and P = .007, comparing respective pregabalin arms to the placebo arm). While some toxicities were significantly more common in the pregabalin arms, being more evident with the higher dose, pregabalin was generally well tolerated by most patients. Conclusion Pregabalin decreases hot flashes and is reasonably well tolerated. A target dose of 75 mg twice daily is recommended. Its effects appear to be roughly comparable to what has been reported with gabapentin and with some newer antidepressants.

Background: The objective of ECOG 1503 was to determine the response rate of this combination in the second-line treatment of advanced NSCLC. Methods: Triapine 105 mg/m2 IV on days 1, 8, and 15, and gemcitabine 1,000 mg/m2 on days 1, 8, and 15, of a 28 day cycle. Results: Eighteen patients enrolled. Three patients were not eligible due to protocol violations. No objective antitumor responses were seen. Three patients (20%) experienced stable disease (90% CI 5.7–44%). Median overall survival: 5.4 months (95% CI 4.2–11.6 months); median time to progression: 1.8 months (95% CI 1.7–3.5 months). Five patients developed acute infusion reactions to Triapine® related to elevated methemoglobinemia. Patients with MDR1 variant genotypes of C3435T experienced superior overall survival compared to non-variants (13.3 vs. 4.3 months, respectively, p = 0.023). Conclusion: This regimen did not demonstrate activity in relapsed NSCLC. Prolonged survival seen with MDR1 variant genotypes is hypothesis-generating.

A field test was conducted at the Hanford site in south-central Washington State to assess the effects of drilling and complex drilling fluids on hydrochemical sampling results. Changes in groundwater chemistry from a pre-test baseline were related to the various fluid components. Chemical species having a source in one or more of the fluid additives increased in concentration, while those not having a source in the fluid decreased in concentration as a result of dilution within the formation. Isotopic species, primarily δ13C and14C, were dramatically affected by the high carbon content of the drilling fluids. The use of complex drilling fluids similar to those used in this test severely limits the usefulness of these environmental isotopes. Attenuation of drilling fluid components in the formation appeared to occur by physical as well as chemical mechanisms. Mass balance calculations indicated that extensive borehole development was required before most fluid components were removed from the formation. Tracers added to, or which were components of, the drilling fluids, were used to evaluate the efficacy of well development. It was concluded that: (1) a 1000-fold decrease in tracer concentration (C/C0 = 10−3) or a development ratio (development volume divided by volume lost during drilling) of 100 is required for many trace constituents; (2) significantly lower development ratios may be adequate for major chemical constituents or in cases where the solute concentration is greater in the formation fluid than in the drilling fluid; (3) extensive development (a development ratio of greater than 100) may be required for certain isotopic species (14C, 36Cl, 129I, etc.). Unless drilling fluid losses are controlled to less than a few thousand liters in the latter case, or a non-contaminated source of drilling fluid is used, the required development may be impractical and/or cost prohibitive.

Chromosome studies were done in 104 patients with various stages of polycythemia vera (PV): 10 had leukemia-myelodysplastic syndrome, 28 had post-PV with myeloid metaplasia (PPVMM), 12 had PV with myelofibrosis, and 54 had PV. Chromosome studies were successful in 86 patients, 37 (43%) of whom had a chromosome abnormality. At diagnosis, 4 of 28 patients (14%) had an abnormal clone; the incidence was 78% in PPVMM and 100% in leukemia-myelodysplastic syndrome. Among the 63 patients with successful chromosome studies during the first 10 years of disease, 27% had an abnormal clone. In contrast, of the 23 patients who had the disease for more than 10 years, 87% had an abnormal clone. Chromosome abnormalities were found in 11 of the 60 patients who either were untreated or underwent only phlebotomy and in 26 of the 44 patients who were treated with myelosuppressive agents. Trisomy 8, +9, and 20q- were found in some patients early during the course of their disease and also among untreated patients. These chromosome abnormalities seem to be related to the natural course of PV rather than to therapy. Patients with a chromosomally abnormal clone at the time of diagnosis of PV had a poorer survival than did those with only normal metaphases. Cytogenetic results did not predict evolution of the disease, but they did provide clues to hematologic phenotype, duration of the disease, and consequences of myelosuppressive therapy.

Purpose To evaluate the outcome of patients with limited-stage small-cell lung cancer (L-SCLC) treated with cisplatin and etoposide (PE), early prophylactic cranial irradiation (PCI), and high-dose twice-daily thoracic radiotherapy (bid RT). Patients and Methods A total of 76 assessable patients were treated on this phase II trial, which included six cycles of PE. PCI (25 Gy/10 fractions) was delivered during cycle 3 to responding patients. Cycles 4 and 5 included concurrent chemotherapy and thoracic RT (30 Gy/20 bid fractions, a 2-week break, and another 30 Gy/20 bid fractions). Results Of the 76 assessable patients, 74 patients (97%) suffered grade 3 or greater (3+) toxicity and 61 patients (80%) had grade 4 or greater (4+) toxicity. Of these adverse events, grade 3+ hematologic toxicity occurred in 72 patients (95%), and grade 3+ nonhematologic toxicity occurred in 55 patients (72%). Only one (2%) of the 61 patients who received PCI experienced treatment failure in the brain. The 5-year survival rate of the 76 assessable patients was 24% (median, 20 months). The 5-year survival rate of the 64 patients who received thoracic RT was 29% (median, 22 months). The 5-year cumulative incidence of in-field treatment failure was 34%. Conclusion This regimen included a high total dose of bid TRT, which resulted in a favorable 5-year survival rate. Local failure remains a problem that will require additional investigation. Newer technology should allow the safe administration of greater doses of RT, which should improve patient outcome. Data from eight trials were combined to demonstrate a relationship between RT dose fractionation and 5-year survival.

A phase II study of the dolastatin 15 analog LU 103793 was conducted by the North Central Cancer Treatment Group in patients with advanced non-small-cell lung cancer (SCLC). Previously untreated patients received this agent at a dosage of 2.5 mg/m2 as a 5-minute intravenous infusion for 5 consecutive days every 3 weeks. Between September 1997 and July 1998, 17 patients were accrued in this study. Forty-two treatment cycles were administered with relatively modest toxicity. No responses were seen. This agent appears to be inactive in the treatment of advanced non-SCLC.

BACKGROUND A large solitary amyloidoma in the cervical epidural space without bony connection and with minimal spinal cord compression and no myelopathy, as a first manifestation of disseminated amyloidosis in a multiple myeloma patient, has not been reported previously; this case is thereby distinct from the seven prior reports in the world literature, of a solitary amyloidoma of the cervical spine. CASE DESCRIPTION A 72-year-old male, recently diagnosed with multiple myeloma, presented with a neuropathy that prompted a screening MRI of the cervical spine. This disclosed a large mass in the upper cervical epidural area felt to pose a high morbidity/mortality risk, leading to successful surgical removal of the amyloidoma mass. This then led to further testing that showed previously unsuspected widespread amyloidosis, which was subclinical up to that time. CONCLUSIONS In patients with a newly discovered amyloidoma, whether or not in the setting of known multiple myeloma, further evaluation should be done to detect the presence of amyloidosis. If the mass is discovered de novo, then an investigation should be carried out to determine if multiple myeloma, as well as amyloidosis, is present.

Background : Docetaxel has activity against multiple malignancies. In a previous ECOG study of untreated patients with multiple myeloma, paclitaxel was found to have mild activity, but had excessive toxicity. Docetaxel was evaluated in patients with relapsing or refractory multiple myeloma. Method : Well-documented patients with relapsing or refractory multiple myeloma, who had received no more than two prior combination chemotherapy regimens, were treated with docetaxel 75 mg m −2 intravenously over 1 h every 3 weeks. Patients were evaluated after two and four cycles of treatment. Standard ECOG criteria were used to evaluate for response and toxicity. Results : The study accrued 31 patients with 28 eligible for response and 30 for toxicity analysis. No objective responses (partial or complete) were found. One patient died due to pneumonia. The majority of patients (80%) developed grade 3–4 granulocytopenia and 23% experienced grade 3–4 thrombocytopenia. The median number of cycles was three. The median survival was 9.9 months. Conclusion : Docetaxel was inactive in patients with relapsing or refractory multiple myeloma. In addition, at 75 mg m −2 every 3 weeks, there was extensive hematological toxicity. It is unlikely that a change in dose or a different schedule would significantly improve response, limit toxicity, and improve survival in patients with multiple myeloma.

Coadministration of eniluracil with 5-fluorouracil (5-FU) allows the oral absorption of small doses of 5-FU, resulting in therapeutic plasma levels. A phase II clinical trial of this combination using a continuous dosing schedule was carried out in patients with metastatic colorectal cancer. Fifty-three previously untreated patients and 46 patients who had received one prior regimen for metastatic disease were enrolled. Patients received 10 mg/m2 of eniluracil and 1 mg/m2 of 5-FU twice daily for 28 days, with cycles repeated after a 7-day rest until progression of disease or prohibitive toxicity. Seven of 53 previously untreated patients had an objective tumor response (13.2%): 1 complete response and 6 partial responses. The mean duration of response was 6.3 months. Only 1 of the 45 evaluable patients in the previously treated group had a partial response, with no complete responses. The duration of response was 3 months. The median progression-free survival was 3.4 months for the previously untreated group and 2.5 months for the previously treated group. Median overall survival was 11.1 months for the previously untreated group and 9.0 months for the previously treated group. Hematologic toxicity was infrequent, with 3 patients experiencing grade 3 toxicity. Incidence of grade 3/4 toxicity included 11 patients with diarrhea, 5 with nausea, and 4 with vomiting. Other common toxicities included anemia and stomatitis, but they were generally mild. This regimen is well tolerated and shows activity in previously untreated patients with metastatic colorectal cancer that is similar to that observed with other 5-FU-based regimens. This regimen has not shown to be effective in patients who have had prior chemotherapy.

This was a single-agent phase II clinical trial of the antifol piritrexim in patients with advanced transitional cell carcinoma of the bladder.Patients with previously-treated, advanced urothelial carcinoma were treated with oral piritrexim at a dose of 25 mg three times daily for 5 consecutive days each week for 3 consecutive weeks followed by a 1-week rest period. Courses were repeated every 28 days.Thirty-five patients were enrolled in the study, with 28 patients evaluable for survival and toxicity and 27 evaluable for response.Myelosuppression was the major dose-limiting toxicity, with WHO grade 3/4 thrombocytopenia in 4 patients, granulocytopenia in 1 patient, and anemia in 3 patients. Grade 3 nonhematologic toxicity consisted of neuropathy in 5 patients, hepatotoxicity in 2, nausea in 2, and 1 each with pulmonary toxicity and rash.Of the 27 patients evaluable for response, 2 (7%) achieved an objective response, lasting 112 and 142 days, respectively.Piritrexim has minimal activity in patients with previously treated transitional cell carcinoma of the bladder, regardless of prior exposure to methotrexate, and further evaluation of this compound in this clinical setting is not warranted.

Visceral involvement usually occurs in the late stages of mycosis fungoides (MF). Small bowel involvement in MF is uncommon. When involved, it could cause significant morbidity and mortality. In this study, the authors present an 89-year-old woman diagnosed with T1, N0, B1, M0; stage 1A MF, treated with topical temovate with good response who presented 3 months later with small bowel obstruction due to biopsy-proven localization of MF in the gastrointestinal tract.

Members of the phylum Microspora are obligate, intracellular, single-celled parasites identified in a wide range of vertebrate and invertebrate hosts. Only a few cases of microsporidial infections have been documented in psittacine birds including peach-faced, masked, and Fischer's lovebirds (Agapornis roseicollis, A. personata, and A. fischeri, respectively), budgerigars (Melopsittacus undulatus), and a double yellow-headed Amazon parrot (Amazona ochrocephala). Parasite identification has typically been limited to phylum or genus, and no avian species of microsporidia has clearly been described. In this report, microsporidia were identified in the kidney and intestine of a new host, the eclectus parrot (Eclectus roratus). Parasites were identified as Encephalitozoon hellem using morphologic, ultrastructural, and small subunit ribosomal RNA gene sequence data obtained from archived tissues. This parasite species was first identified in immunocompromised humans and may be a potential zoonotic pathogen. The epidemiology and prevalence of this parasite in humans and birds should be further explored.

Axons are particularly at risk in human diffuse head injury. Use of immunocytochemical labeling techniques has recently demonstrated that axonal injury (AI) and the ensuing reactive axonal change is, probably, more widespread and occurs over a longer posttraumatic time in the injured brain than had previously been appreciated. But the characterization of morphologic or reactive changes occurring after nondisruptive AI has largely been defined from animal models. The comparability of AI in animal models to human diffuse AI (DAI) is discussed and the conclusion drawn that, although animal models allow the analysis of morphologic changes, the spatial distribution within the brain and the time course of reactive axonal change differs to some extent both between species and with the mode of brain injury. Thus, the majority of animal models do not reproduce exactly the extent and time course of AI that occurs in human DAI. Nonetheless, these studies provide good insight into reactive axonal change. In addition, there is developing in the literature considerable variance in the terminology applied to injured axons or nerve fibers. We explain our current understanding of a number of terms now present in the literature and suggest the adoption of a common terminology. Recent work has provided a consensus that reactive axonal change is linked to pertubation of the axolemma resulting in disruption of ionic homeostatic mechanisms within injured nerve fibers. But quantitative data for changes for different ion species is lacking and is required before a better definition of this homeostatic disruption may be provided. Recent studies of responses by the axonal cytoskeleton after nondisruptive AI have demonstrated loss of axonal microtubules over a period up to 24 h after injury. The biochemical mechanisms resulting in loss of microtubules are, hypothetically, mediated both by posttraumatic influx of calcium and activation of calmodulin. This loss results in focal accumulation of membranous organelles in parts of the length of damaged axons where the axonal diameter is greater than normal to form axonal swellings. We distinguish, on morphologic grounds, between axonal swellings and axonal bulbs. There is also a growing consensus regarding responses by neurofilaments after nondisruptive AI. Initially, and rapidly after injury, there is reduced spacing or compaction of neurofilaments. This compaction is stable over at least 6 h and results from the loss or collapse of neurofilament sidearms but retention of the filamentous form of the neurofilaments. We posit that sidearm loss may be mediated either through proteolysis of sidearms via activation of microM calpain or sidearm dephosphorylation via posttraumatic, altered interaction between protein phosphatases and kinase(s), or a combination of these two, after calcium influx, which occurs, at least in part, as a result of changes in the structure and functional state of the axolemma. Evidence for proteolysis of neurofilaments has been obtained recently in the optic nerve stretch injury model and is correlated with disruption of the axolemma. But the earliest posttraumatic interval at which this was obtained was 4 h. Clearly, therefore, no evidence has been obtained to support the hypothesis that there is rapid, posttraumatic proteolysis of the whole axonal cytoskeleton mediated by calpains. Rather, we hypothesize that such proteolysis occurs only when intra-axonal calcium levels allow activation of mM calpain and suggest that such proteolysis, resulting in the loss of the filamentous structure of neurofilaments occurs either when the amount of deformation of the axolemma is so great at the time of injury to result in primary axotomy or, more commonly, is a terminal degenerative change that results in secondary axotomy or disconnection some hours after injury.

Methane occurs as a dissolved constituent in groundwater from confined aquifers in the Columbia River Basalt Group, Columbia basin, Washington. Isotopic compositions of methane in groundwater indicate that the methane is a mixture of biogenic (^dgr13C-CH4 to -88^pmil and ^dgr2H-CH4 to -265^pmil) and thermogenic (^dgr13C-CH4 to -35^pmil, and ^dgr2H-CH4 to -134^pmil) components. Chemical and isotopic data are consistent with entrainment of deep, coal-bed-generated methane in upwelling groundwater from below the Columbia River Basalt Group (>4 km) that mixes with near-surface groundwater. The areal distribution pattern of methane suggests that fault intersections are necessary for vert cal migration of deep methane through the basalt. This study suggests that deep subbasalt coal-bed methane in the Columbia basin has infiltrated the shallow basalt groundwater system, and isotopic analyses of methane in groundwater from structurally favorable locations can be used to identify potential exploration targets. The wide areal distribution of methane in this large, relatively unexplored frontier province suggests economic gas reserves.

Paroxysmal nocturnal hemoglobinuria (PNH) is recognized as a clonal disorder manifested as increased sensitivity of marrow cells to complement. Case reports have associated this condition with leukemia, myelodysplasia, and myeloproliferative disorders. We identified 47 patients with PNH from 1976 to 1990. In 9 of the 47 patients, PNH was associated with another clonal myelopathy. Five patients had PNH and a myelodysplastic syndrome, and four had PNH and agnogenic myeloid metaplasia. PNH preceded the development of myelodysplastic syndrome but occurred after the development of agnogenic myeloid metaplasia. This is the largest series of PNH and other clonal myelopathies. We suggest that the PNH defect may represent a second manifestation of a single stem cell disorder.

9513 Background: Hot flashes are a major problem in many women for which better treatment options are needed. Given the known efficacy of gabapentin for decreasing hot flashes, it was decided to evaluate pregabalin, with hopes that it would work better and/or with fewer toxicities. Methods: A three-arm, double-blinded, placebo-controlled randomized trial was developed. Women with bothersome hot flashes (at least 28/week) were randomized to receive either a placebo or target pregabalin oral doses of 75 mg bid or 150 mg bid (starting at 50 mg/d and then increasing the dose at weekly intervals to 50 mg bid, then 75 mg bid, and then, in the higher dose arm, 150 mg bid); patients were treated for 6 weeks. Hot flash numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flash diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intra-patient difference in hot flash score between baseline and week six, comparing the higher dose pregabalin arm and the placebo arm. With the planned sample size of 55 patients per arm, there was an 80% power and two-sided 5% Type I error rate to detect a difference of 0.54 standard deviations, or 1.08 hot flashes per day, or 2.7 units of hot flash score per day. Results: 207 patients were randomized between 6/20/2008 and 8/21/2008. The study arms were well balanced. Mean/median daily hot flash scores and frequencies for all pts at baseline were 15.7/13.4 and 8.3/7.7, respectively. The table shows the decreases in hot flashes from the baseline to the sixth treatment week. Larger numbers illustrate greater hot flash reductions. Toxicity information, quality of life information, and information regarding the effects of hot flashes on subjective symptoms will be available at the meeting time. Conclusions: Pregabalin reduces hot flashes in women. There appears to be similar effects with both studied doses. [Table: see text] No significant financial relationships to disclose.

7544 Background: NCCTG N0028 was a trial that determined the MTD of RT that could be given with carboplatin & paclitaxel was 74 Gy/34 fractions. This secondary analysis was performed to determine the survival of pts treated on this trial. Methods: Eligible pts had medically or surgically unresectable NSCLC, PS=0–1, weight loss No significant financial relationships to disclose.

A polymerase chain reaction assay was developed for detection of budgerigar fledgling disease virus (BFDV). The assay used a single set of primers complementary to sequences located in the putative coding region for the BFDV VP1 gene. The observed amplification product had the expected size of 550 bp and was confirmed to derive from BFDV DNA by its restriction digestion pattern. This assay was specific for BFDV and highly sensitive, being able to detect as few as 20 copies of the virus. By using the polymerase chain reaction, BFDV was detected in adult, nestling, and embryo budgerigar (Melopsitticus undulatus) tissue DNAs and in sera from adult and nestling budgerigars. These results suggest the possibility of persistent infections in adult birds and lend further support to previously described evidence of possible in ovo transmission. BFDV was also detected in chicken embryo fibroblast cell cultures and chicken eggs inoculated with the virus. A 550-bp product with identical restriction enzyme sites was amplified from a suspected polyomavirus isolated from a peach-faced lovebird (Agapornis pesonata) and from tissue DNA from a Hahn's macaw (Ara nobilis) and a sun conure (Aratinga solstitialis) with histological lesions suggestive of polyomavirus infection. These fragments also hybridized with a BFDV-derived probe, proving that they were derived from a polyomavirus very similar, if not identical, to BFDV.

1071 Background: N0234 is a phase II trial of gemcitabine at 1000 mg/m2 days 1 and 8 of a 21 day cycle and erlotinib at 150 mg daily in patients with previous therapy with either an anthracycline or a taxane for MBC. A partial response (PR) rate of 17% has been reported (ASCO 2005). Recent information suggests that over-expression of the EGFR pathway is frequent in patients with TNeg MBC. Methods: Tissue and serum were obtained for translational studies of ER, PR, HER2, and proteins related to EGFR pathway on tissue using immunohistochemistry; CK19, mammoglobin, and TTK on circulating tumor cells (CTCs). Markers were evaluated centrally, blinded to patient outcome. Complete data were available in 57 of 59 eligible patients; 20/57 patients (pts) were TNeg. Results: A PR rate of 25% and clinical benefit rate (PR + stable disease > 6 months)of 25% was observed in TNeg pts as compared to a PR rate of 14% (p = 0.30) and clinical benefit rate 22% (p= 0.75) for non-TNeg pts. Median progression free survival 72 days vs 98 days (p=0.13) and overall survival 227 days vs 738 days (p [Table: see text]

644 Background: Based on favorable preclinical interaction of the HER1 inhibitor erlotinib with chemotherapy, and previously demonstrated single agent activity of gemcitabine as therapy for metasta...