tbuckley/cabot-search huggingface dataset:
Prolonged bevacizumab exposure accompanied by EGFR activation in colorectal cancer (CRC) models to provide a rational for combinations of bevacizumab and erlotinib in the GERCOR DREAM phase III trial.
Authors: Annette K. Larsen, Aimery de Gramont, Thierry André, Christophe Tournigand, Ariel Savina, Aude Batistella, Virginie Poindessous, Paul Mésange
Journal: Journal of Clinical Oncology (2014)

449 Background: Combinations of EGFR and VEGF(R)-targeted agents have consistently shown at least additive activity in preclinical CRC models when the targeted agents were administered alone (Larsen et al., Pharmacol Therap. 131:80, 2011; Poindessous et al., Clin Cancer Res. 17:6522, 2011) paving the way for the GERCOR DREAM-OPTIMOX3 phase III trial in metastatic CRC. Although use of EGFR-directed mAbs are counter-indicated in CRC patients with mutant KRAS, the situation is less clear for EGFR-targeted TKIs like erlotinib. Methods: Three human CRC xenograft models expressing wt KRAS/BRAF, mutant KRAS or mutant BRAF were established in nude mice. Animals were treated with bevacizumab and erlotinib, alone or in combination, and the influence on tumor growth, viability and the presence of phosphorylated ErbB/HER family members was determined. Treatment-related toxicity was estimated by weight loss. Results: Combinations of bevacizumab and erlotinib were significantly more active than either agent alone for all three xenograft models although the advantage of combining the two agents was particularly striking for the KRAS/BRAF wt xenograft model. Unexpectedly, erlotinib alone showed strong antitumor activity in the BRAF mutant HT-29 xenograft model. The bevacizumab plus erlotinib combination was less toxic, as determined by weight loss, compared to erlotinib alone. Interestingly, IHC analysis showed that bevacizumab activates EGFR in all three xenograft models. Conclusions: We here report that bevacizumab and erlotinib combinations are significantly more active than either agent alone in CRC models with different KRAS and BRAF status. We further demonstrate that bevacizumab activates EGFR signaling similar to what has been described for irinotecan and ionizing radiation. Taken together, our findings suggest that mutant KRAS and BRAF have lesser influence on the sensitivity to EGFR-targeted TKIs than is the case for the EGFR directed mAbs and provide a mechanistic basis for the increased activity of the bevacizumab and erlotinib combination.
Tumor regression by means of iron oxide cytostatic drug targeting.
Authors: M. G. Krukemeyer, W. Wagner, M. Jakobs, J. H. Hartlapp, V. Krenn
Journal: Journal of Clinical Oncology (2011)

e13502 Background: Tumor therapy has become more individual with improved outcome and minor side effects. Methods: Our new concept consists of iron oxide (Fe3O4) coupled to mitoxantrone applied to mice and men with metastatic mammarian carcinoma. Iron has a strong affinition to the RES, which can be found in the liver and spleen. Therefore the combination of fluid iron and cytostatic will achieve a high concentration in the liver and a smaller in the peripheral blood. The iron content of the tissue samples was determined by atomic absorption measurement. Results: After evaluating the results of our animal study a 70-year old female patient with massive liver metastases who was not an adequate candidate for systemic chemotherapy had been treated with nanotherapy. The concentration of the ferrofluid was 10.5 mg/mL and 0.6 mg of mitoxantrone/mL. Pharmacokinetic profiles of mitoxantrone bound to nanoparticles are not yet available. A total of 0.8 mg of mitoxantrone/kg of bodyweight was chosen as the dosage, because we achieved the best results in previous animal tests with this dosis. Measurement of the total iron in the blood was 151 µg/dL in contrast to 440 µg/dL in the liver. There was no evidence of dissolution of the drug from the particles. Within 4 weeks the patient achieves a partial remission and the reduction of tumor mass of about 90% was stable during May 2008 to March 2009. Corresponding to the measurement we found in our MRI-images in the liver and the spleen a T2 shortening as a clear sign of iron deposition. There was a drop in leukocytes two weeks after therapy and the leukocytes value has recovered within weeks. The patient displayed no other clinical symptoms. Conclusions: In our animal studies and in our clinical case we had been able to show that nanoparticles accumulate in the liver and in the spleen in high concentration in contrast to other organs and the blood. Furthermore it was shown that tumor shrinking occurs with only small side effects. Sterilization of the coupled iron is technically difficult, but therapy itself is easy. Therefore this new technique can be a therapeutic option for secondary tumors of the liver to reduce tumor mass with higher cytostatic concentrations and less adverse effects for the patients.
Randomized trial of a lifestyle intervention for women with early-stage breast cancer (BC) receiving adjuvant hormone therapy: Initial results.
Authors: R. Segal, G. R. Pond, M. Vallis, M. Dion, K. I. Pritchard, J. A. Ligibel, M. N. Levine, P. J. Goodwin
Journal: Journal of Clinical Oncology (2011)

512 Background: Obesity is an adverse prognostic factor in early BC. We conducted a randomized clinical trial (RCT) to evaluate a 2-year, centrally delivered, telephone-based weight loss intervention (WLI) compared to a mailed educational intervention (EI) on recurrence, weight loss and QOL in postmenopausal women receiving adjuvant Letrozole. The trial was terminated after 338 of a planned 2,150 women were enrolled due to loss of funding. Methods: 338 women with stage I-IIIa BC were randomized to WLI (n%171) or EI alone (n%167) at 20 centers in Canada and USA. Eligibility included BMI ≥24 kg/m2and <3 years of definitive surgery. WLI involved 19 calls, mailings and a participant manual. Weight loss goal was 10% of baseline via reduction of caloric and fat intake (500-1000 kcal/day, 20% calories fat) and increased physical activity (150-200 minutes/week). Results: Mean age and BMI were 61 years and 31.3 kg/m2. Baseline BMI, adjuvant chemotherapy, and tumor characteristics were balanced between arms. 87.5% of protocol mandated WLI calls took place. Mean weight change is shown in the table. Results were similar for baseline BMI ≥/<30 kg/m2 and adjuvant chemotherapy (yes/no). Mean SF 36 normalized physical component score was improved in WLI vs. EI at 6 (+ 4.1 WLI vs. + 2.1 C, p%0.046) and 12 months (+3.9 WLI vs. + 2.7 EI, p%0.33). Conclusions: A 2-year, telephone-based WLI resulted in significant weight loss at 6, 12, and 18 months in early BC. Results were similar with BMI <30 or 30+ and with or without adjuvant chemotherapy. Follow-up continues to evaluate longer term effects. Funded by Novartis Pharmaceuticals Inc. Sponsored by the Ontario Clinical Oncology Group. Weight (kg) Weight loss intervention Educational intervention P value N Mean (sd) N Mean (sd) Baseline 171 82.7 (15.3) 167 81.3 (14.5) 6 months % Change from baseline 147 -5.6 (4.9) 142 -0.8 (4.9) <.001 12 months % Change from baseline 113 -6.1 (6.2) 121 -0.6 (6.0) <.001 18 months % Change from baseline 68 -5.0 (7.6) 77 -1.2 (6.5) .003
Esophageal cancer gender disparity.
Authors: Luckson Noe Mathieu, Norma Kanarek, Craig Hooker, Charles M. Rudin, Malcolm Brock
Journal: Journal of Clinical Oncology (2012)

47 Background: Over the past thirty years, esophageal cancer (EC) incidence has been increasing more rapidly than any other solid neoplasm in the Western world. Globally, there is a large male predominance in both esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). The reasons for this gender difference and the possible role of estrogen are unclear. We conducted an analytical epidemiological study to determine if estrogen exposure explains the male predominance in observed esophageal cancer incidence. Methods: We evaluated the SEER cancer incidence and trends from 1975 to 2008 using SEER Stat to calculate the annual percentage change (APC) in each ten-year age group and in EAC and ESCC by gender. Results: Male predominance in incidence rates of EC was most evident in the younger group and those with EAC histology. The rate of increase for EAC incidence in post menopausal females is greater than in any other demographic category. This increasing incidence rate in the post menopausal female was also observed in the ESCC, but to a lesser extent. The APC was negative (-1.5) between 1975-2008 only in the 50-64 age female group. The negative APC in the female 50-64 years age group may be due to the increased use of exogenous hormonal therapy since 1975 for this age group. Interestingly, the APC was positive (increasing) in the 65+ age females. Conclusions: Using age as a proxy for estrogen exposure, our findings suggest a hormonal reason for the observed age-related, declining male to female EC incidence rate ratios. It also confirms gender differences in incidence long observed in EC and suggests that estrogen may serve as a preventative agent against EC. Moreover, this protective role of estrogen may dissipate with time if post menopausal estrogen use is discontinued. We have initiated a subset analysis of the nine individual SEER sites’ database to confirm the above findings by location and plan to further assess the relationship of both endogenous and exogenous estrogen via hormonal therapy use in EC incidence in the Women’s Health Initiative cohort. Our epidemiological observation of gender-age differences warrants translation into a molecular study with the use of sophisticated biomarkers to establish the seemingly protective role of estrogen in esophageal cancer.
Imatinib Mesylate and Hyper-CVAD (IM-HCVAD) for Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL).
Authors: Martha Arellano, Disni Muringampurath-John, Pareen J. Shenoy, Elliott F. Winton, Beverly Bryan, Amelia Langston, Rajni Sinha, Morgan L. McLemore, Leonard Heffner, H. Jean Khoury
Journal: Blood (2009)
Acquired mutations associated with ibrutinib resistance in Waldenström macroglobulinemia
Authors: Lian Xu, Nicholas Tsakmaklis, Guang Yang, Jiaji G. Chen, Xia Liu, Maria Demos, Amanda Kofides, Christopher J. Patterson, Kirsten Meid, Joshua Gustine, Toni Dubeau, M. Lia Palomba, Ranjana Advani, Jorge J. Castillo, Richard R. Furman, Zachary R. Hunter, Steven P. Treon
Journal: Blood (2017)
Making steps to decrease emergency room visits in patients with cancer: Our experience after participating in the ASCO Quality Training Program.
Authors: Brian Hunis, Alvaro Jose Alencar, Aurelio Bartolome Castrellon, Luis E. Raez, Vedner Guerrier
Journal: Journal of Clinical Oncology (2016)

51 Background: Overutilization of emergency room services by oncology patients is a known problem associated with increased admission rates and health care expenditure. A review of our oncology patients’ emergency room (ER) visits from January to May 2015 demonstrated that 48% of ER visits happened during office hours. Consequently a rapid cycle quality improvement project was developed with an aim to decrease ER visits by 30% by September 2015. Methods: A multidisciplinary team completed an action plan, starting with a project charter and definition of aim statement. A process map for patient scheduling/triage was created. A cause and effect diagram helped identify potential causes patient utilization of the ER. Diagnostic data were obtained querying our EMR (EPIC) for ER visits from January to May 2015. A Pareto chart identified Breast, Hematology and GI malignancies as main diagnosis utilizing the ER. Plan-do-study-act (PDSA) #1 began with development of a protocol to guide the handling of patients' calls that could previously resulted in an ER visit. Staff from the patient access center (PAC), a telephone operator service, and physicians’ offices were trained on its application. PDSA #2 focused on patient education to the importance of contacting the PAC for any concern or symptom related to active chemotherapy treatment. Results: The implementation of a triage system at our PAC resulted in a 60% decrease in the number of patients utilizing the ER, which met our goal. Patients’ calls to the PAC have increased. Two new materials were developed: a telephone triage form categorizing the patient’s complaint and the resulting action by our PAC center staff, and a patient Clinical Intervention Triage Tracking Log which allowed for the tracking of all patients triaged, their data, and the responsible team member. Conclusions: This study suggests that the development of a tool to properly identify and address emergent chemotherapy symptoms without utilizing the ER during working hours resulted in an intervention that positively affected the pre-specified endpoint.
Clinical/pathologic characteristics of diabetic patients with early breast cancer (BC) and their survival outcome.
Authors: S. Seber, G. Basaran, T. Korkmaz, F. Telli, M. Kocar, M. Kanitez, F. Dane, P. F. Yumuk, N. S. Turhal
Journal: Journal of Clinical Oncology (2011)

e11019 Background: Diabetes mellitus is thought to be associated with adverse outcomes in BC and it might adversely affect decisions regarding treatment. Methods: We retrospectively reviewed the medical records of the early BC patients (pts) who were treated at Marmara University Hospital between 1999 and 2007. We noted the patient, tumor, treatment-related characteristics and information on comorbidities from the medical charts. We investigated whether patient and tumor related parameters were different between diabetic and non-diabetic BC patients and whether diabetes has a negative impact on survival outcome. Results: We identified 33 diabetic early BC pts among 456 pts (7%) who had received their adjuvant therapy in our center. All diabetic BC pts were on oral antidiabetics. The median age of our study group was 51 (23-85) and median follow up was 48 months. Most diabetic BC pts were postmenopausal (p:0.004); diabetic pts were older (p:0.04) and have smaller tms compared to non-diabetic early BC pts (p:0.00). Diabetic pts have higher grade tumors (p:0.03) and multifocal tumors were more common in diabetic pts compared to non-diabetic BC patients (p:0.02). T size, stage, nodal involvement, LVI, ER/PR and Her-2 status and diabetes were found to have significant impact on DFS in the univariate analyses. Only stage of the disease retained its significant impact on DFS in the multivariate analysis. Stage, LVI and nodal status were found to have significant impact on OS in the univariate analyses. Conclusions: Either more frequent hospital visits or improvements in diabetes care might be responsible from smaller tumors and less relapses in diabetic early BC pts.
Prediction of late recurrences by breast cancer index in the NCIC CTG MA.17 cohort.
Authors: D. Sgroi, E. Carney, E. Richardson, L. Steffel, S. N. Binns, D. M. Finkelstein, L. E. Shepherd, N. C. Kesty, C. Schnabel, M. G. Erlander, J. N. Ingle, P. Porter, S. Paik, H. B. Muss, K. I. Pritchard, D. Tu, P. E. Goss
Journal: Journal of Clinical Oncology (2011)

2 Background: The MA.17 trial demonstrated that extended adjuvant endocrine therapy with letrozole after 5-y of tamoxifen markedly reduced the risk of recurrence in women with ER+ early stage breast cancer. This trial provides an opportunity to assess the ability of biomarkers to predict late recurrences in ER+ breast cancer. The Breast Cancer Index (BCI), a continuous risk index based on the combination of HOXB13:IL17BR (H:I) and the molecular grade index (MGI), estimates the individual risk of recurrence in ER+ breast cancer patients. In this study, the prognostic utility of BCI to predict late recurrences was examined. Methods: FFPE tumor blocks were collected from patients who experienced a breast cancer recurrence up to unblinding of MA.17. Controls were matched 2:1 for age, tumor size, nodal status and prior chemotherapy, and were disease free for longer than cases. All cases were reviewed for standard histopathology and evaluated using the real-time RT-PCR BCI assay. Results: Patient characteristics for the case-control study were similar to that from the overall study. Characteristics for cases (N=83) and controls (N=166) were not significantly different except for treatment. A higher percentage of controls compared to cases tended to be categorized as low risk by BCI (58% vs 43%), while a lower percentage of controls than cases tended to be categorized as high risk by BCI (34% vs 24%). In univariate analysis, treatment, BCI, H:I and HOXB13, but not tumor grade or MGI, were significant predictors of late recurrence. After adjusting for standard variables (age, tumor grade and treatment), BCI (OR 2.37; P=0.03), H:I (OR 2.55; P=0.04) and HOXB13 (OR 1.35; P=0.02) remained significant predictors of recurrence. HOXB13 expression at diagnosis predicted patient benefit from extended endocrine therapy with letrozole. Conclusions: In this case-controlled study, the data demonstrate that BCI is a significant predictor of late recurrences in ER+ patients following 5-y of tamoxifen. The prognostic performance of BCI to predict late recurrences was largely dependent on HOXB13 expression. The integration of H:I and MGI within BCI provides prognostic utility for both early and late recurrences.
A provider-based quality improvement intervention aimed at improving appropriateness of radiation therapy regimens for patients with advanced cancer and painful bone metastases.
Authors: Anne M. Walling, Phillip Beron, Neil Wenger, Patrick Kupelian, Tania Betty Kaprealian, Susan Ann McCloskey, Christopher R. King, Michael L. Steinberg
Journal: Journal of Clinical Oncology (2016)

176 Background: Although guidelines suggest that shorter course radiation treatments for patients with advanced cancer and painful bone metastases are most appropriate, treatment patterns in the United States are inconsistent with this approach. Methods: We implemented a provider-focused intervention at a university-based radiation oncology practice aimed at improving rates of shorter-course radiation treatments for patients with advanced cancer and painful bone metastases. The intervention involved key leaders of the practice participating in a RAND/UCLA Appropriateness Panel to review the latest guidelines and evidence and judge appropriateness of various treatment regimens as it pertained to their practice. These results were compared to current (7/2012-6/2013) practice patterns and presented to the faculty group. This exercise informed a template-based point of care intervention led by a clinical champion and leadership that focused on key aspects of clinical and patient-centered care including whether the bone metastases were complicated or uncomplicated, patient prognosis, extent of disease, and travel distance for the patient to the treatment site. We compared rates of lower burden treatment regimens (less than 10 fractions) for 81 pre-intervention patients with 107 metastases treated between 7/2012-6/2013 and 75 post-intervention patients with 94 metastases treated between 5/2015-1/2016. Results: Overall, painful bone metastases were treated with less than 10 fractions more often in the post-intervention period (38% v. 63%, p &lt; 0.001). Uncomplicated bone metastases treated with conformal radiation were also more likely to be treated with less than 10 fractions in the post intervention period (19% v. 52%, p &lt; 0.001). One quarter of metastases were treated with SBRT during both the pre and post-intervention periods. Conclusions: Leadership support, provider engagement in integrating guidelines into practice, and a note template with point of care clinical reminders can improve rates of appropriate, low-burden radiation oncology treatments for patients with advanced cancer.
A Rare Case of Omentum Invasive Prostate Cancer
Authors: Rahul Ladwa, Sonja Gustafson, Elizabeth McCaffrey, Kenneth Miles, Kenneth O’Byrne
Journal: Clinical Nuclear Medicine (2017)

The omentum is a rare metastatic site for prostatic adenocarcinoma. We present a case of metastatic castrate-resistant prostate cancer, with progressive omentum invasive prostate cancer identified on prostate-specific membrane antigen (PSMA) PET/CT scan. Omental biopsy revealed metastatic prostate adenocarcinoma, and cabazitaxel chemotherapy was instituted with a prostate-specific antigen biochemical response. Repeat PSMA PET/CT imaging revealed increased avidity in omental metastasis. Despite prostate-specific antigen response, PSMA PET/CT did not correlate with a therapeutic response.
Gallbladder carcinoma: Institutional experience—Is this a rare disease?
Authors: R. R. Segovia, J. J. Zarba, J. Arcuri, E. Stegmayer, A. P. Medina, L. De Gregorio, D. Gonzalez, S. Holgado, S. Perez
Journal: Journal of Clinical Oncology (2011)

e14550
Development of a decision support aid to support goals of care conversation for hospitalized patients with cancer.
Authors: Marina Ciny George, Lisa E Stone, Karen Stepan, Colleen M. Gallagher, Jessica Anne Moore, Susan Gaeta, Margaret W. Meyer, Robert Joseph Volk, Donna S. Zhukovsky
Journal: Journal of Clinical Oncology (2016)

42 Background: Goals of care (GOC) conversations between oncologists and patients are often ill-defined due to poor physician and patient preparation and unclear goals. Hospitalization may further increase patients’ fear and confusion about GOC. Creating a tool to facilitate shared decision making is critical to support patients and their health care team in this process. In this study, we have collected data as the initial step in the development of a decision aid (DA) for GOC conversations with hospitalized patients with advanced cancer. Methods: A group of 14 content experts including diverse health professionals, patients and caregivers responded to a needs assessment to determine key questions to elicit involved stakeholders’ perceptions on relevant content for the DA. Questions were used to conduct semi-structured interviews with patients, a clinician focus group and a patient and caregiver focus group. All responses were audio-recorded and transcribed. Results: There were 30 participants: 10 patient interviews and 10 participants in each focus group. Patients generally wanted as much information as possible about prognosis and choices, but acknowledged they were often overwhelmed and frustrated at not receiving information sooner. Most were clear about who they would include in their GOC discussions. Clinicians’ concerns included not destroying patients’ hope and uncertainty about how to achieve the delicate balance of delivering bad news while preserving hope. Clinicians also felt challenged by the time needed to conduct GOC conversations and how to initiate them. Patient and caregivers emphasized the value of a multimodal approach to GOC conversations. Individually, they varied in their readiness for and the ideal timing of GOC conversations, noting these could be early or late in their illness trajectory. Conclusions: We see a need for personalization in a decision support aid to have clear goals of care. Patients differ in readiness to activate different parts of the decisional tree at different times. This will be used to guide design of a decision support aid to support hospitalized patients with advanced cancer to have a meaningful goals of care conversation with their clinicians.