tbuckley/cabot-search huggingface dataset:
Degarelix versus LHRH agonists: Differential skeletal and urinary tract outcomes from an analysis of six comparative randomized clinical trials.
Authors: E. David Crawford, Neal Shore, Kurt Miller, Bertrand Tombal, Cathrina Kathrup, Egbert van der Meulen, Bo-Eric Persson
Journal: Journal of Clinical Oncology (2013)

68 Background: The use of ADT in men with prostate cancer is well established. GnRH antagonists have a mode of action distinct to that of LHRH agonists and comparative trials have shown differences in efficacy and safety between these agents. Adverse events (AE) from the musculoskeletal and renal and urinary systems have now been analysed. Methods: Results were pooled from 6 prospective, comparative randomised trials (n=2328). Most patients (pts) received 1 year of degarelix or LHRH agonist treatment (n=1686); the remaining men had 3–7 months’ treatment (n=642). AEs were analysed using Kaplan Meier plots and a log-rank test for homogeneity on relevant groups of MedDRA terms. Results: Treatment groups (degarelix, n=1491; LHRH agonist, n=837) were balanced for baseline characteristics such as age, testosterone, PSA and disease stage. In men with metastatic disease alkaline phosphatase (ALP) was reduced to a greater extent with degarelix (p=0.0373) throughout the year. Overall probability of fracture (&lt;1% vs. 2%, p=0.0411) and incidence of joint related AEs (4% vs. 6%, p=0.0116) were significantly lower for degarelix-treated men. Incidence of muscle or bone pain was lower for degarelix (9% vs. 12%, p=0.0822). Incidence of urinary infections (UI) was reduced (5% vs. 8% with agonists) and time to first UI was significantly increased (p=0.0010) with degarelix. Overall probability of any renal or urinary tract AEs, including lower urinary tract symptoms (LUTS), was significantly lower in pts receiving degarelix (p&lt;0.0001). Consistent with fewer skeletal and urinary tract AEs indicating better disease control, men with baseline PSA &gt;50 ng/mL had significantly higher PSA PFS compared to agonist treated pts. OS during 1 year of treatment was significantly higher for degarelix pts (98.3% vs. 96.7%, p=0.0329). Conclusions: This analysis of 2,328 men shows degarelix-treated men had lower ALP, significantly fewer fractures, a lower incidence of urinary tract symptoms and higher overall survival than pts receiving an LHRH agonist over one year. Control of such disease symptoms is consistent with previous data on a significantly lower risk of PSA PFS during the first year of treatment.
Variation of hepatitis C virus genotype distribution between geographically related patients: A retrospective multicenter study.
Authors: H. A. Torres, M. Nevah-Rubin, B. J. Barnett, P. Mahale, D. P. Kontoyiannis, L. Mishra, M. Hassan, I. I. Raad
Journal: Journal of Clinical Oncology (2011)

8052 Background: According to the nucleotide sequence of the viral genome, hepatitic C virus (HCV) shows considerable genetic heterogeneity. HCV genotypes vary geographically, with different distribution observed in various countries. In the United States, genotypes 1a and 1b are the most prevalent variants followed by genotypes 2 and 3. Despite the carcinogenetic role of HCV, the distribution of HCV genotypes in cancer patients as compared to non cancer patients has not been evaluated. Methods: A total of 636 patients with chronic HCV infection were evaluated at three academic institutions in Houston, (01/2008-12/2009). Demographic, epidemiological, and viral data were retrieved from medical records. Results: According to patients’ underlying disease, patients were classified into cancer patients (N=129), immunocompetent (N=333), and HCV-HIV coinfected (N=102). Overall, genotype 1 (G-1) was the predominant infecting type (82%); however, the distribution varied among the 3 patient groups. Only 66% of cancer patients had G-1 infection compared to 84% of immunocompetent (P = 0.00004) or 99% of HCV-HIV coinfected patients (P < .00001). More cancer patients had G-2 and G-3 infections compared to the other groups. Cancer types included 53 hematological malignancies and 76 solid tumors. Age, gender, risk factors for acquiring HCV infection, duration of infection, and place of residency were comparable between cancer and immunocompetent patients. G-1 predominated (84%) in immunocompetent as compared to patients with hepatocellular carcinoma (74%, P = .08) or lymphoma (59%, P = .001). G- 2 was more prevalent in patients with lymphoma (24%) compared to immunocompetent (8%), P = .003; yielding a three-fold increase in cancer risk among HCV-infected patients than other genotypes (OR: 3.72, 95% CI:1.38-9.76). Conclusions: This multicenter retrospective study provides initial evidence of the different distribution for HCV genotypes among geographically related infected patients and suggests a greater carcinogenic potential of some variants. Large-scale prospective studies are warranted to ascertain these findings in other geographical regions.
Adult survivors of childhood cancer: Development of a regional transistions program.
Authors: Jennifer R. Klemp, Kristin A. Stegenga, Wendy McClellan, Hope Krebill, Robin Ryan, Mukta Sharma, Jyoti Panicker, Joy M. Fulbright, Becky Lowry, Eve-Lynn Nelson
Journal: Journal of Clinical Oncology (2013)

217 Background: With increased survival rates, adult survivors of childhood cancers (ASCC) face lifelong screening and healthcare needs. Given increasing costs and demands across healthcare institutions, there is a significant need for survivorship models that emphasize regional collaboration, transition of pediatric patients to adult care, and focus on survivor-centered outcomes. Specific aims: Over the last two years, the presenters developed and implemented a survivor-centered regional approach to meet ASCC needs, addressing system, provider, and survivor barriers to successful transition and ongoing ASCC care. Methods: The presenters will describe community engagement strategies utilized to build a successful, sustainable survivor-centered approach across the region. The Midwest Cancer Alliance (MCA), the outreach arm of University of Kansas Cancer Center (KUCC), provides a supportive, neutral environment to bridge institution-specific concerns. Interdisciplinary teams from Children’s Mercy Hospital and University of Kansas’ Pediatrics department developed a formal working group with KUCC adult-focused partners. The group has taken an inclusive approach, bringing together pediatric and adult healthcare teams as well as expertise in outreach, patient navigation, telemedicine, education, and evaluation/research. Emphasis will be placed on how the team has prioritized needs-driven deliverables across metropolitan and rural communities. Results: The transitions program has maintained monthly working group meetings; completed a survivor needs assessment and disseminated findings; and initiated a cross-institutional transitions clinic. The team is collaborating on a comprehensive survivorship training approach to educate regional healthcare providers. The presenters will describe the team’s performance improvement processes to monitor outcomes and continuously refine the ASCC/AYA model. Conclusions: Community engagement is an ideal platform for regional program development to meet ASCC survivor needs. Future steps include measuring program outcomes, working toward EHR integration, increasing survivor input, and incorporating education into residency/fellowship training.
Treatment outcomes of metastatic melanoma in the elderly patients: A retrospective analysis.
Authors: U. P. Hegde, R. B. Everson, L. Wilson, J. Mercado, P. Kerr, J. Grant-Kels
Journal: Journal of Clinical Oncology (2010)

e19028 Background: Cutaneous melanoma (CM) incidence is rapidly rising in the elderly population resulting in treatment challenges and increased economic burden. Although old age is a marker of poor prognosis of melanoma, aging associated co morbidities, cognitive decline and social isolation confound the outcome results. This report describes our experience of treating elderly patients (pts) with metastatic melanoma (MM). Methods: Between October 2002 and October 2008, 26 elderly pts with MM, 16 males and 10 female, median ages 75 years (yrs), range 60- 90 yrs were treated at the University of Connecticut Health Center after informed consent on a standard treatment. Metastatic sites included soft tissue and or lymph nodes and or lung (13 pts) and liver and or brain and or bones (13 pts). 22 pts opted for treatment and received either single agent temozolomide (3 pts), combined chemotherapy containing carboplatin, vinblastine, temozolomide (CVT) (10 pts) or CVT plus interferon (IFN) (3 pts), high dose interleukin 2 (IL2), (2 pts), biochemotherapy (3 pts) or metastatectomy with tumor derived heat shock protein vaccine (clinical trial) (1 pt). Four pts declined treatment and were followed up (included in survival analysis). Results: All pts tolerated treatments well with expected side effects and no treatment associated mortality. The overall response rate is 58% (15 out of 26), with complete response in seven pts (27%), partial response in 8 pts (31%), progressive disease in 9 pts (35%) and stable disease in 3 pts (12%). The median survival (MS) of all patients is 15 months (mths) (range 3-74 mths). During 7 year follow up period, 17 pts have died of progressive disease while 9 pts are surviving (6 with disease and 3 with no evidence of disease). The median survivalof surviving patients is 15 mths (range 7-74 mths); while those who died of disease are 12 mths (range 4-18). Conclusions: Our experience suggests that elderly patients with metastatic melanoma respond to standard chemotherapeutic agents used either alone or in combination resulting in improved clinical outcomes in some. Laboratory studies are underway to understand biologic relevance of clinical responses of melanoma in elderly patients. No significant financial relationships to disclose.
A multi-institutional feasibility study of S-1/oxaliplatin (SOX) plus bevacizumab in patients with advanced/metastatic colorectal cancer: HiSCO-02 prospective phase II study.
Authors: Manabu Kurayoshi, Katsunori Shinozaki, Takao Hinoi, Tsuyoshi Kobayashi, Manabu Shimomura, Masanori Yoshimitsu, Kazuhiro Toyota, Masahiro Nakahara, Yasuyo Ishizaki, Yuzo Hirata, Shinya Kodama, Yosuke Shimizu, Koji Kawaguchi, Masakazu Tokunaga, Daisuke Sumitani, Hideki Ohdan
Journal: Journal of Clinical Oncology (2015)

728 Background: mFOLFOX6 regimen, which is a standard regimen for metastatic colorectal cancer (CRC), is inconvenient owing to its requirement for continuous infusion via vascular access. We aimed to investigate the efficacy and safety of S-1/oxaliplatin (SOX) plus bevacizumab, a promising alternative treatment to replace mFOLFOX6. Methods: We undertook a clinical phase II trial in 12 institutions in Hiroshima, Japan. We enrolled individuals aged 20–80 years who had metastatic CRC, had an Eastern Cooperative Oncology Group performance status (PS) of 0 or 1, had assessable lesions, and had received no previous chemotherapy. Eligible patients were assigned SOX plus bevacizumab (S-1: 80-120 mg/body/day, day 1–14 orally administrated, oxaliplatin: 130mg/m 2 day 1 i.v., bevacizumab: 7.5mg/kg day 1 i.v. q3w). The primary endpoint was response rate (RR), and the secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Results: From May 2011 to January 2014, 55 patients (mean age, 64 years) were enrolled. The number of metastatic organs were one: 29 cases (52.7%), two or more: 25 cases (45.4%), and 2 cases had no target lesions (3.6%). Median follow up time was 12.8 months (range, 1.4-38.6 months). RR was 45.4% (95% CI, 32.2%-58.6%) and disease control rate was 87.3% (95% CI, 78.5-96.1%). Median PFS and OS time were 9.2 months (95% CI, 7.6-10.8) and 22.0 months (95% CI, 17.7-26.2), respectively. The median number of cycles of chemotherapy was 7 (range, 1-16). The median relative dose intensity of oxaliplatin, S-1, and bevacizumab were 85%, 85%, and 87%, respectively. Major toxic effects (grade 3/4) were thrombocytopenia (5.7%), neutropenia (7.5%), sensory neuropathy (13.2%), and anorexia (17.0%). Conclusions: These data indicated that the SOX plus bevacizumab regimen is effective and well tolerated in patients with metastatic CRC. Clinical trial information: UMIN000004976.
Targeted sequencing of upper tract urothelial carcinoma.
Authors: John P. Sfakianos, Philip H. Kim, Gopa Iyer, Eugene K. Cha, Emily C. Zabor, A. Ari Hakimi, Sasinya N. Scott, Ricardo Ramirez, Aphrothiti Hanrahan, Jonathan E. Rosenberg, Hikmat Al-Ahmadie, Guido Dalbagni, Dean F. Bajorin, Michael F. Berger, Bernard H. Bochner, David B. Solit, Jonathan A. Coleman
Journal: Journal of Clinical Oncology (2014)

309 Background: Regardless of the anatomic location (renal pelvis or ureter (upper tract), bladder or urethra) urothelial carcinoma is considered a single entity. Outcomes differ depending on site of initial diagnosis. Moreover, little is known about the comparative biology across primary sites. To define the genomic profile of urothelial carcinoma arising from the upper tract, we used a next generation sequencing technology to analyze 26 sporadic high-grade urothelial tumors of the renal pelvis. Methods: Frozen tumor samples and matched germline blood or normal kidney DNA from 26 nephroureterectomy specimens were obtained under an IRB-approved protocol. DNA was analyzed using a next generation, targeted sequencing assay. We compared these tumors to a set of 108 bladder tumors. Fisher’s exact test analyzed associations with pathological stage and Cox regression with log-rank p-values examined associations with bladder recurrence and disease-free survival. Fisher’s exact test was used to compare mutation frequencies between upper tract and bladder tumors. P-values were adjusted for multiple comparisons using the Benjamini-Hochberg method. Results: Surgical pathology was Ta, T1, T2 and T3 in 7 (26.9%), 5 (19.2%), 4 (15.4%) and 10 (38.5%) patients, respectively. High-grade disease was found in 24 (92.3%) patients with 6 (27.3%) patients having node positive disease. The most frequently altered genes included FGFR3 (42.3%), KDM6A (38.5%), MLL2 (26.9%), TSC1 (26.9%), CREBBP (23.1%), CDKN2A (19.2%) and HRAS (19.2%). No significant differences in tumor and patient characteristics were found between the bladder and upper tract cohorts. A significant difference in the frequency of alterations between the upper tract and bladder cohorts was found in HRAS (19.2% vs 2.8%, p=0.032), TP53 (7.7% vs 57.4%, p&lt;0.001) and TSC1(26.9% vs 5.6%, p=0.024). Conclusions: We identified unique patterns of genomic alterations within upper tract urothelial carcinoma compared to bladder cancers. Upper tract tumors are characterized by a higher frequency of activating FGFR3 and HRAS mutations, TSC1 nonsense mutations, and a lower frequency of TP53 alterations. These findings may have future implications on the utility of targeted therapies in this disease subtype.
Predictors of primary dose reduction (PDR) among patients (pts) age 65 and older receiving adjuvant chemotherapy (chemo).
Authors: H. D. Klepin, A. Gajra, M. Hardt, W. P. Tew, S. G. Mohile, C. Owusu, C. P. Gross, S. M. Lichtman, R. Ramani, V. Katheria, J. Brown, R. Jayani, K. Hansen, K. Togawa, S. Klapper, F. L. Wong, A. Hurria
Journal: Journal of Clinical Oncology (2011)

9003 Background: Adjuvant chemo is given with curative intent; however, older pts are at increased risk for toxicity (tox). Oncologists may empirically reduce doses in 1st cycle due to concerns regarding tox risk. We studied the factors associated with PDR among older pts receiving adjuvant chemo and evaluated the association of PDR with tox outcomes. Methods: We conducted a secondary data analysis of a prospective, multi-site cohort study of pts ≥65 prescribed adjuvant chemo (Hurria et al, ASCO 2010). Chemo regimen and dosing (per MD discretion) were categorized as standard (SD) or PDR (reduced in 1st cycle) per NCCN guidelines. We studied the sociodemographic, tumor and treatment characteristics, and geriatric assessment factors (GA) (functional status, comorbidity, social support, psychosocial, cognitive and nutritional status) associated with PDR using bivariate and multivariate logistic regression. Differences in grade 3-5 toxicity between PDR and SD were compared. Results: 172 pts (median age 72 (range 65-89), 63% female) with Stage I-III cancer [31% gastrointestinal, 18% gynecologic (GYN), 22% breast, and 19% lung] were included in this analysis. Approximately 15% (N= 26) received PDR. Pts receiving PDR (in comparison to SD) were older (median 80 vs. 71 yrs, p<.01), more often widowed (42% vs. 21%, p=.02), had a higher prevalence of GYN CA (35% vs. 15%, p=.03) and a lower prevalence of breast CA (4% vs. 25%, p=.02), were more likely to have osteoporosis (39 % vs. 16%, p=.01), and had a lower mean MD-rated KPS (83 vs. 88, p=.02). In multivariate analysis, only older age (OR 1.17; CI 1.07-1.27) was independently associated with PDR. Grade 3-5 tox was observed in 50% of pts with PDR and 55% with SD. There were no differences in grade 3-5 hematologic, non-hematologic tox, hospitalization, dose reduction or delays. Conclusions: One in seven older pts treated with curative intent had a PDR; PDR use was primarily associated with increased age. Tox remains high despite PDR. Prospective data is needed to investigate the benefit (ameliorating tox) to risk (impacting efficacy) ratio of PDR in older adults receiving chemo for curative intent.
Extramedullary disease (EMD): A common terminal pathway in multiple myeloma (MM) progression.
Authors: S. Z. Usmani, A. Mitchell, J. Szymonifka, J. D. Shaughnessy, A. Hoering, Y. Alsayed, S. Waheed, B. Nair, J. Crowley, B. Barlogie
Journal: Journal of Clinical Oncology (2011)

8068 Background: Therapeutic advances have extended MM survival so that ~50% of newly diagnosed patients can expect to be living 10yr after treatment initiation. In our clinical practice, EMD is a rare primary disease manifestation but appears to evolve with repeated relapses. Methods: Our MM database was interrogated for patients treated between 1989-2010 presenting with EMD pre-transplant (EMD-1), or developed EMD at relapse (EMD-2). We focused on 936 patients in TT protocols, 240 patients in non-TT protocols and 789 non-protocol patients who had baseline PET scans prior to transplantation at MIRT (total n=1965). Results: EMD-1 sites >10% included Chest-Wall, Liver, Lymph Nodes, Skin/Soft Tissue and CNS. EMD-2 showed a preponderance of liver disease (34.3% EMD-2 v 21.2% EMD-1). Median EFS/OS were shorter in EMD-1 (EFS: 1.1 v 5.0 yrs, p< 0.001; OS: 1.2 v 7.3 yrs, p< 0.001). EMD-1 was documented in 2.41% of TT protocol patients, 4.35% non-TT protocol patients and 4.5% non-protocol patients, while 5-yr post-transplant estimates totaled 3.43% TT protocol patients, 5.2% non-TT protocol patients and 7.24% non-protocol patients. EMD-1 patients were compared to non-EMD patients using Fisher's exact or Chi-square tests. EMD-1 was significantly linked to GEP-defined risk, pre-transplant cytogenetic abnormalities (CA), low levels of hemoglobin and low platelet counts. Cumulative incidence of EMD at 5 years from transplant increased for GEP-defined high risk patients (11.5% vs 2.0%, p<0.001) as well as with pre-transplant CA (7.0% vs 4.1%, p=0.004). GEP data was available for 46 EMD and 1105 non-EMD patients, along with19 samples from EMD sites. Conclusions: While uncommon at presentation, EMD-2 represents a common terminal pathway of MM, linked with increased hepatic preponderance. Cumulative incidence of EMD was significantly increased in GEP-defined high-risk MM at baseline and associated with grave prognosis. We are evaluated available GEP data to determine any distinguishing features that may predict EMD potential on baseline GEP samples, as well as uncover differences between concomitant random marrow GEP and EMD-GEP at time of EMD presentation (data to be presented).
Communication regarding chemotherapy-induced anemia and related fatigue: Recommendations from an observational linguistic study
Authors: H. E. Hamilton, D. Blum, D. Cella, B. Davidson, L. Nail, R. J. Waltzman
Journal: Journal of Clinical Oncology (2005)

8047 Background: Many instruments exist for determining the impact of chemotherapy-induced anemia and related fatigue on patient quality-of-life, but there are few studies that analyze how health care providers actually discuss anemia and fatigue with patients. Methods: Letters of invitation were mailed to over 1,000 community-based oncologists; of these, 15 met the criteria and agreed to participate in this research study. Thirty-six of their patients undergoing chemotherapy were video- and audio-recorded during their regularly scheduled visit. Post-visit interviews were conducted separately with patients and participating physicians, and/or allied health professionals. Interviews were transcribed and analyzed using validated sociolinguistic techniques. Results: Fifty-two percent of visit time was spent discussing side effects and symptoms; of that time 60% was spent discussing hematologic issues (anemia and related fatigue, blood counts, growth factors, etc.). In spite of this, most discussions of fatigue/anemia lacked specificity and the “benchmarking” necessary to determine true impact on patients’ lives. For example, the word “normal” was used in 67% of visits, but without clarity to its reference (i.e., without reference to “normal symptom for a patient with cancer”, “normal side effect for chemotherapy”, etc.). Physician inquiries regarding fatigue also tended to be too focused and brief to elicit patients’ chief concerns. On average, less than 1 question/visit relating to fatigue/anemia was asked of the patient; 90% of these questions required only a yes/no answer. No fatigue-assessment instrument was used or referenced, in whole or in part, in any visit. Conclusions: Chemotherapy-induced anemia and related fatigue were discussed, but not with the specificity or depth required to understand impact on quality-of-life. Community-based oncologists are encouraged to modify their vocabulary (e.g., use “expected” in lieu of “normal”), and consider incorporating a simple fatigue instrument, either within the consult or filled out prior to the consultation, to improve the quality of communication. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ortho-Biotech Ortho-Biotech Ortho-Biotech