tbuckley/cabot-search huggingface dataset:
Lymphovascular invasion in clinical stage I testicular nonseminoma: Potential marker of more aggressive relapses and implications for active surveillance.
Authors: C. R. Nichols, S. Daneshmand, S. Tyldesley, K. N. Chi, N. Murray, A. I. So, P. C. Black, B. M. Hayes-Lattin, C. K. Kollmannsberger
Journal: Journal of Clinical Oncology (2011)

4654 Background: The dominant factor associated with risk of recurrence for patients (pts) with CSI nonseminoma (CSI NS) is presence or absence of lymphovascular invasion (LVI+, LVI-) at the time of orchiectomy with LVI+ pts having about a 50% and LVI- pts a 15% risk of recurrent disease after orchiectomy. LVI is used in a number of guidelines to drive risk-adapted strategies such as intense and prolonged active surveillance for LVI- and adjuvant BEP for LVI + pts. Methods: Our IRB-approved population-based database from Oregon and British Columbia was reviewed. Our current clinical guidelines recommend active surveillance for all CSI pts and thus we have a large population of both LVI + and LVI- pts who did not receive active therapies after orchiectomy. All CSI pts were reviewed and clinical characteristics of relapse were correlated with LVI. Results: 59/223 consecutive pts with CSI NS relapsed on active surveillance. Detailed pathological information was available on 49/59 pts. All 59 pts relapsed with IGCCC good prognosis disease. Median follow-up for the entire group was 43 months. Clinical characteristics of relapsing LVI- and LVI+ CSI NS pts. Conclusions: These results are consistent with the hypothesis that LVI+, CSI NS pts harbor more biologically aggressive disease that is marked by significantly diminished risk of late relapse (beyond 1 year) (p=0.017), and, perhaps, a higher incidence of disseminated relapses. Both LVI- and LVI+ pts appear to be sensitive to chemotherapy at the time of recurrence with a 100% disease specific survival in both groups. These results need to be confirmed by analysis of additional large aggregated data sets of LVI+ and LVI- pts (anticipated by May 2011). If confirmed, patterns of active surveillance could be altered to more precisely align risk periods with imaging schedules. Initial characteristics Stage at relapse Time to relapse Embryonal cell predominant Marker + at dx Stage II Stage III 1-6 mo. 7-12 mo. 13-18 mo. 18-24 >24 mo. LVI- n=19 58% 69% 18 95% 1 5% 11 58% 4 21% 2 11% 0 2 11% LVI+ n=30 73% 63% 27 90% 3 10% 26 87% 4 13% 0 0 0
Gentuzumab Ozogamicin (GO:Mylotarg) Monotherapy for Relapsed AML after Hematopoietic Stem Cell Transplantation: from Morphological Target to Molecular Target.
Authors: Shuichi Miyawaki, Nahoko Hatsumi, Takumi Hoshino, Toshihide Kawamura, Satoru Takada, Tohru Sakura
Journal: Blood (2007)
Long-term outcomes of cisplatin-based chemotherapy in patients with stage II-III germ cell tumors: Center 30-year experience of a single center.
Authors: Guillermo De Velasco, Daniel E. Castellano, Juan Manuel Sepúlveda, Felipe Villacampa, Tomas Pascual, Ray Manneh, Lucia Parrilla, Carlos A. Farfán, Hernan Cortes-Funes
Journal: Journal of Clinical Oncology (2013)

338 Background: We retrospectively assessed long-term outcomes of cisplatin-based chemotherapy for stage II/IIII germ cell tumors (GCTs) at Medical Oncology Department of 12 Octubre University Hospital, Madrid (Spain). Methods: Two hundred fourteen (214) consecutive males with advanced GCTs of the testis or extragonadal origin who received standard cisplatin-based chemotherapy regimens between 1982 and 2012 were analyzed. Results: Demographic features: Median age 26.4 years (range 14- 72 years). Right and left testicular tumor present in 71 (37%) and 78 (41%) patients respectively and cryptorchidism in 11 (5%). Histology: 12% of the patients had seminomatous and 88% non-seminomatous histology. Stage distribution (TNM): Stage II 105p (49%), Stage III 109 p (51%). Twenty-five primary (11%) were extragonadal. Risk assessment according to IGCCCG - good 115 p (54%) intermediate 34 p (16%) and poor 62 p (29%). All patients received chemotherapy with cisplatin (BEP-73%, EP-15%, BOPM-EPI 5%, PVB 6%, others 1%). Survival analysis: The median follow-up period was 117 months (0 - 329). Totally, 158 patients (74%) achieved complete remission (CR). CR was achieved in 128 p (60%) after induction therapy (first line chemotherapy). Salvage treatment: surgery +/-chemotherapy was given to 72 (33%) and 85 (39%) patients respectively. High-dose chemotherapy (with carboplatin based- schemes at dosage (AUC20) as salvage therapy was performed in 65 patients (30%). Of them 35 p (53.4%) had complete remission of disease without relapse and the median progression free survival was of 47.2 months. Severe AEs were &lt; to 5%, and classically already described renal impairment, ototoxicity and neurophaty with non chemotherapy-related toxic deaths. Conclusions: Improvement of medical management and survival during platinum-based chemotherapy and the development of several regimens for salvage chemotherapy seemed to contribute to improving outcomes of patients with advanced GCTs even for patients with platinum-refractory disease. However, we continue to investigate in the search for genetic and molecular mechanisms that help us change it.
Utilizing Ki67 score to predict optimal liver-directed treatment in patients with metastatic neuroendocrine tumors.
Authors: Smit Singla, Kristopher Attwood, Charles Levea, Garin Tomaszewski, Boris W. Kuvshinoff, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2015)

370 Background: Patients with metastatic neuroendocrine tumors (NETs) benefit from treatment with yttrium-90 radioembolization (Y-90) or transarterial chemoembolization (TACE), however the criteria for patient selection are not well defined. We sought to determine if the proliferative index (Ki67 score) could be utilized to select patients for one therapy over the other. Methods: A single institution analysis of all patients treated with Y-90 or TACE between 2001 and 2014. Pathologists blinded to clinical information performed Ki67 scoring, and the data was analyzed using multivariate association for survival outcomes. Results: Amongst 72 patients (M: 39, F: 33; median age, 57 years) included in the study, the most common site of tumor origin was small bowel (n=35, 49%), and the most common histology subtype was carcinoid (n=58, 85%). Forty-four patients were treated with Y-90 (61%) and 28 patients received TACE (39%). Ki67 score was available in 28 patients (64%) treated with Y-90 and 16 patients (57%) in the TACE group. In Y-90 group, there was a higher concomitant use of sandostatin (94% vs 75%, p=0.023), longer time between diagnosis and treatment (median, 32 vs 11 months, p=&lt;0.001), and less number of total treatments completed (89% vs 46%, p&lt;0.001). There was no significant difference in overall survival (OS) between the groups (median, 69 vs 82 months, respectively; p=0.477); however when adjusted for Ki67 score of 3, patients with Ki67 score &gt;3% were found to have better OS when treated with Y-90 as compared to TACE (HR, 0.083; CI, 0.008-0.854). On the other hand, in patients with Ki67 &lt;3%, OS was better when treated with TACE (HR, 13.5; CI, 1.2-148.8). Further, patients in Y-90 group had higher incidence of carcinoid syndrome (39% vs 21%, p=0.195) and bilobar liver disease (95% vs 89%, p=0.371), whereas hepatic tumor burden &gt;25% was greater in the TACE group (26% vs 20%, p=0.614), but these differences were not significant. Conclusions: In patients with metastatic NETs, Ki-67 score &gt;3% may be predictive of treatment benefit with Y-90 and &lt;3% with TACE. A longer time from diagnosis and an increased number of prior therapies may indicate a need for aggressive therapy; however a prospective validation is warranted.
Does apathy impact cancer patient symptom burden?
Authors: C. P. Escalante, M. A. Kallen, P. H. Morrow, E. F. Manzullo, J. D. Duffy, R. U. Valdres
Journal: Journal of Clinical Oncology (2010)

e19598 Background: Apathy, or lack of motivation, has been little studied in cancer patients. Because interventions for Cancer-Related Fatigue (CRF) often include behavioral change and involve commitment to treatment, patient apathy may be detrimental to outcome success. We conducted an observational study in our CRF Clinic and report on 110 patients evaluated for apathy. Our objectives were to investigate associations between apathy and fatigue-related symptoms and determine if clinically apathetic patients differed from the non-apathetic in symptom burden. Methods: New CRF patients were evaluated for apathy using the Apathy Evaluation Scale, Clinician Version (AES-C) as primary outcome measure. The AES-C provides a continuous apathy score (range 18-72); scores can also be used to categorize patients as apathetic or non-apathetic (AES-C ≥ 38 reflects clinically significant apathy). To explore apathy and fatigue symptom associations, AES-C scores were correlated (Spearman's rho) with five symptoms commonly experienced by CRF patients (fatigue, pain, depression, anxiety, sleep disturbance), and level of symptom burden was compared (Mann-Whitney U) across apathetic vs. non-apathetic patients. Results: Of the 110 new CRF patients evaluated for apathy, median age was 60 years (range 24-92), 69% (n=76) were female, 76% (n=84) white, and 68% (n=75) married. The most frequent cancer diagnoses were breast (35%, n=38) and leukemia/lymphoma/myeloma (18%, n=20). Median apathy score was 26 (range 18-61), with 22% (n=24) identified as clinically apathetic. Apathy was statistically significantly (p<.05) associated with fatigue, depression, and anxiety (rho=.34, .48, .30, respectively). Apathetic patient symptom burden was statistically significantly (p<.05) greater than the non-apathetic for fatigue (BFI 7.2 vs. 5.6), depression (BDI-II 22.4 vs. 12.6), and anxiety (BAI 16.4 vs. 11.0). Conclusions: Patient apathy is associated with fatigue, depression, and anxiety, while patients identified as apathetic experience increased symptomatic burden. Thus, apathy may undermine patient CRF treatment objectives. Future investigations include determining factors involved in the development of patient apathy and identifying methods to reduce or eliminate it. No significant financial relationships to disclose.
Long-term health outcomes of germ cell tumor survivors.
Authors: Trent James Miller, Lawrence H. Einhorn, Nasser H. Hanna, Victoria Champion, Patrick Monahan, Timothy E. Stump, Mary J. Brames, Somer Case-Eads
Journal: Journal of Clinical Oncology (2016)

135 Background: Survivors of germ cell tumors (GCT) may face long-term health risks We have previously reported the high incidence of hypogonadism (HG) in survivors of GCT. These patients also may be at risk for other chronic health and psychosocial problems. Methods: Patients treated with chemotherapy (Group 1) or with orchiectomy and/or other surgery or radiotherapy for GCT (Group 2), were 18-50 yrs of age, and not receiving supplemental testosterone at baseline were eligible. Total testosterone was measured at baseline. For patients receiving supplemental testosterone while on study, total testosterone was also measured at 3 and 6 months. Cancer diagnosis and treatment variables were obtained from medical records. Patients completed a validated quality of life (QOL) questionnaire at baseline, 3, and 6 mos. Measures included the Aging Males’ Symptoms (AMS) scale and NIH Patient Reported Outcome Management Information Systems (PROMIS) measures. Results: The rate of HG ( &lt; 300 testosterone) at baseline did not differ between Group 1 and Group 2 (p = 0.45). Compared to non-HG, patients with HG measured at baseline were significantly more likely to have a BMI in the obese ( &gt; 30; 57% vs 19%) range (p &lt; 0.001). Improvements in testosterone during treatment from baseline to follow-up were strongly correlated with improvements in AMS (r = 0.51, p = 0.001) and moderately correlated with improvements in general health (r = 0.32, p = .049). Multivariable models using baseline variables demonstrated that baseline HG was significantly associated with worse baseline quality of life in the areas of general health, sleep quality, and fatigue. BMI in the obesity range was significantly associated with worse general health. Conclusions: Patients who were treated for GCT are at higher risk of HG. This subsequently increases the risk of having a BMI in the obese range, which in turn is associated with worse QOL. Treating HG is associated with improvements in AMS scale.
Analyses of the Inducible Cyclic Adenosine 3′,5′-Monophosphate Early Repressor (ICER) and cAMP Response Element Binding Protein (CREB) in HL60 Cells: New Insight Leukemogenesis?.
Authors: Martina Pigazzi, Elena Manara, Marta Campo DellOrto, Emanuela Ricotti, Giuseppe Basso
Journal: Blood (2006)
Feasibility and acceptability of a novel web portal to enhance legacy building for adults with advanced cancer.
Authors: Jennifer Kim Bernat, Shelley A. Johns, Linda F. Brown, Nancy E. Hook, Sandra Althouse, Paul R. Helft
Journal: Journal of Clinical Oncology (2014)

140 Background: Being diagnosed with advanced cancer is a painful reality encompassing physical, psychosocial, and spiritual challenges as death draws near. Some patients cope resiliently, while others struggle. Dignity therapy (DT) is an empirically supported intervention where patients reflect on meaningful memories and values during interviews. These interviews are transcribed into a legacy project (LP) that can be edited and shared with loved ones. DT has been shown to benefit patients and LP recipients; however, it requires resources to implement and is not widely available in community settings. We developed a narrative intervention based on DT using a novel web portal (ZarpZ) to disseminate the LPs. This pilot assesses the feasibility, acceptability, and efficacy of our intervention to determine if it could be an affordable, user-friendly, and accessible alternative to traditional DT. Methods: Adults (n=16) with advanced-stage solid malignancies participated in a therapist-led intervention including (1) a modified DT session; (2) orientation to ZarpZ; and (3) brief weekly phone calls to aid self-led online LP building. We collected baseline and post-intervention data on primary (acceptability) and secondary (existential well-being, dignity, demoralization, peaceful acceptance of illness, and family communication) outcomes. Results: 69% of participants completed a LP. Participants reported high satisfaction with the LP created (100%) and with the intervention, particularly the home visit with the interventionist (81%). Participants were less satisfied with ZarpZ—only 45% used it. Among ZarpZ users, 40% reported it as somewhat difficult to use. Our sample was not distressed at baseline; thus, post-intervention secondary outcomes did not significantly differ from baseline. Conclusions: Participants found value in the intervention and in the LPs created, but were generally dissatisfied with ZarpZ. Future research should aim to improve usability. Since our sample size was small and participants were not distressed at baseline, we were not able to show significant improvement in secondary outcomes. Future research should examine these outcomes in a larger and more distressed sample.
Geriatric assessment (GA) of older patients with cancer in Australia: A national, multicenter audit.
Authors: S. S. Joshi, C. B. Steer, J. Yoong, R. Lakhanpal, S. Kirsop, T. Dunlop, L. R. Mileshkin, D. Yip, G. M. Marx, E. J. Hovey, S. Della-Fiorentina
Journal: Journal of Clinical Oncology (2011)

9134 Background: It is recommended that all older patients presenting for oncology opinion undergo a geriatric assessment. This may guide intervention, alert clinicians to problems and predict treatment toxicity and outcome. The rate of geriatric assessment in Australia is unknown. Methods: This is a multicentre audit in 2 parts: a retrospective file review and prospective audit of case presentations at multidisciplinary meetings (MDMs). Patients aged over 70 years presenting to a medical oncology clinic or being discussed at an MDM were eligible. Documentation of initial consultation with an oncologist was reviewed. Any mention of a GA domain was noted. These domains included: Activities of Daily Living (ADLs), Instrumental ADLs (IADLs), geriatric syndromes (eg cognitive impairment, falls), social support, polypharmacy and creatinine clearance (CrCl). Data was collected at six oncology centres in Victoria, NSW and Canberra (ACT). Results: Data was collected from 251 file reviews and 108 MDM discussions in a total of 304 patients. Median age 76 years (range 70-95). Treatment was proposed in 72% of file reviews and 80% of MDMs. Factors known to affect outcome like performance status (PS) (62%), comorbidities (98%), living alone or with someone (88%) and social support (73%) were most frequently assessed at initial consult with an oncologist. Other domains like mention of any ADL (56%), IADL (36%), geriatric syndrome (30%), CrCl (17%) and polypharmacy (30%) were not as frequently assessed. A formal comorbidity score (eg Charlson index) was never used. Only 1 patient had all components of ADLs and IADLs assessed. Treatment was withheld on the basis of age alone in 5 patients. GA domains mentioned at MDMs were comorbidities (84%), living alone/with someone (30%), social support (24%), ADLs (23%), PS (19%), polypharmacy (13%), geriatric syndromes (10%), IADL (6%) and creatinine clearance (3%). Conclusions: This multicentre audit of Australian medical oncology practice is the first documentation of the rate of routine GA in patients aged over 70 years. There is significant room for improvement. Education regarding the importance and utility of routine GA may improve the assessment of some GA domains.
Vulvar cancer: Presentation and treatment variation among races.
Authors: Jennifer Rosin, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2013)

5611 Background: Vulvar cancer is the fourth most common gynecologic malignancy. We analyzed variation among races in treatment, histology and stage at presentation using the National Cancer Database (NCDB). Methods: Between 2000 and 2010, 51,157 women from 1338 hospitals across the US were reported to the NCDB with vulvar cancer. Differences were assessed using Chi square analysis. Results: Caucasian patients with vulvar carcinoma in situ received no first course treatment significantly less than African American or Hispanic patients (3% vs 6% and 7%, p&lt;0.05). No treatment for stage I and II vulvar cancer was also significantly less than African American patients (1.4% vs 2.5%, p&lt;0.05). African Americans overall chose radical surgery less often than Caucasians (13% vs 16%, p&lt;0.05), but local tumor excision more (29% vs 24%, p&lt;0.05). African Americans and Hispanics chose no surgery of primary sites significantly more than Caucasians (14% and 15% vs 9%, p&lt;0.05). As expected, squamous cell carcinoma accounts for over 90% of vulvar cancer cases reported. However, Asian-Pacific Islanders had a significantly higher proportion of Extramammary Paget’s disease when compared to Caucasians, African Americans, or Hispanics (20% vs 4.3%, 0.6%, 3.2%. p&lt;0.05). African Americans had the lowest proportion of Extramammary Paget’s compared to any other race for all stages (0.6%, p&lt;0.05). African Americans presented as vulvar carcinoma in situ more often than any other race (33% vs 25-29%, p&lt;0.05). Conclusions: This is the largest study analyzing racial differences in treatment, histology and stage at presentation in women with vulvar cancer. Caucasians were least likely to opt for no first course treatment overall. African Americans were most likely to choose no treatment and, when having surgery, preferred local excision over radical vulvectomy.
Dnmt3a and Tet2 interact to Repress differentiation lineage-specific transcriptional factors in Hematopoietic Stem Cells By the Regulation of Epigenome
Authors: Xiaotian Zhang, Mira Jeong, Jianzhong Su, Myung Gon Ko, Yun Huang, Hyun Jung Park, Anjana Rao, Wei Li, Margaret A. Goodell
Journal: Blood (2014)
Preoperative chemoradiotherapy for locally advanced rectal adenocarcinoma: A dosimetric comparison of intensity-modulated radiation therapy (IMRT) with three-dimensional conformal radiotherapy (3D-CRT).
Authors: C. T. Tao, L. M. Scala, H. Gee, D. Lim, B. Padilla, M. C. Rounsaville, J. W. Lee, R. E. Abendroth
Journal: Journal of Clinical Oncology (2011)

615 Background: Small bowel and bladder toxicities (bleeding, obstruction, perforation, and stricture) are rare but serious late complications of pelvic radiotherapy (RT) related to dose received by these organs. IMRT has been used effectively in other pelvic malignancies (prostate and gynecologic) to decrease the dose to normal tissues when compared to 3D-CRT. Few studies have examined the use of IMRT in rectal cancer to assess whether a similar dose reduction is feasible. Methods: Eight consecutively treated patients with T2/T3 and N0/N1 rectal adenocarcinoma underwent 5-FU based neoadjuvant chemo-RT using 7-field sliding-window IMRT between 2008 and 2010. Retrospectively, conventional 4-field 3D-CRT plans were generated for dosimetric comparison with IMRT treatment plans. Planning target volumes included the gross tumor, rectum, peri-rectal tissues, pre-sacral space, and common and internal iliac lymphatics. Organs at risk included small bowel (contoured as all small bowel identified on the planning CT plus a 1 cm symmetrical expansion), bladder, and femoral heads. Small bowel, bladder, and femoral head mean doses and volumes receiving 45 Gy (V45) were compared between conventional and IMRT plans, respectively. Paired Student's t-test was used for statistical analysis. Results: Mean prescription dose was 52.9 ± 3.3 Gy. Compared to 3D-CRT, IMRT plans had an 11% lower mean dose delivered to the bladder (38.2 ± 4.5 Gy vs 43.1 ± 1.9 Gy, p = 0.028) and 24% lower mean dose to the small bowel (24.0 ± 2.9 Gy vs 31.7 ± 7.7 Gy, p = 0.014). IMRT plans also had a 55% lower bladder V45 (27 ± 19% vs 61 ± 22%, p = 0.0077) and a 96% lower small bowel V45 (1 ± 0% vs 21± 20%, p = 0.021). The femoral heads received a nonsignificant higher mean dose (19.2 ± 3.9 Gy vs 16.6 ± 3.0 Gy, p = 0.069). Conclusions: Small bowel and bladder volume receiving 45 Gy and mean dose were significantly lower using IMRT compared with 3D-CRT planning. More stringent volumetric planning constraints may be necessary to further reduce the dose to the femoral heads. Further study is warranted to examine the clinical benefit of these dosimetric findings. No significant financial relationships to disclose.