tbuckley/cabot-search huggingface dataset:
Intravesical rAd–IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin–Refractory or Relapsed Non–Muscle-Invasive Bladder Cancer: A Phase II Randomized Study
Authors: Neal D. Shore, Stephen A. Boorjian, Daniel J. Canter, Kenneth Ogan, Lawrence I. Karsh, Tracy M. Downs, Leonard G. Gomella, Ashish M. Kamat, Yair Lotan, Robert S. Svatek, Trinity J. Bivalacqua, Robert L. Grubb, Tracey L. Krupski, Seth P. Lerner, Michael E. Woods, Brant A. Inman, Matthew I. Milowsky, Alan Boyd, F. Peter Treasure, Gillian Gregory, David G. Sawutz, Seppo Yla-Herttuala, Nigel R. Parker, Colin P.N. Dinney
Journal: Journal of Clinical Oncology (2017)

Purpose Many patients with high-risk non-muscle-invasive bladder cancer (NMIBC) are either refractory to bacillus Calmette-Guerin (BCG) treatment or may experience disease relapse. We assessed the efficacy and safety of recombinant adenovirus interferon alfa with Syn3 (rAd-IFNα/Syn3), a replication-deficient recombinant adenovirus gene transfer vector, for patients with high-grade (HG) BCG-refractory or relapsed NMIBC. Methods In this open-label, multicenter (n = 13), parallel-arm, phase II study ( ClinicalTrials.gov identifier: NCT01687244), 43 patients with HG BCG-refractory or relapsed NMIBC received intravesical rAd-IFNα/Syn3 (randomly assigned 1:1 to 1 × 1011 viral particles (vp)/mL or 3 × 1011 vp/mL). Patients who responded at months 3, 6, and 9 were retreated at months 4, 7, and 10. The primary end point was 12-month HG recurrence-free survival (RFS). All patients who received at least one dose were included in efficacy and safety analyses. Results Forty patients received rAd-IFNα/Syn3 (1 × 1011 vp/mL, n = 21; 3 × 1011 vp/mL, n = 19) between November 5, 2012, and April 8, 2015. Fourteen patients (35.0%; 90% CI, 22.6% to 49.2%) remained free of HG recurrence 12 months after initial treatment. Comparable 12-month HG RFS was noted for both doses. Of these 14 patients, two experienced recurrence at 21 and 28 months, respectively, after treatment initiation, and one died as a result of an upper tract tumor at 17 months without a recurrence. rAd-IFNα/Syn3 was well tolerated; no grade four or five adverse events (AEs) occurred, and no patient discontinued treatment because of an adverse event. The most frequently reported drug-related AEs were micturition urgency (n = 16; 40%), dysuria (n = 16; 40%), fatigue (n = 13; 32.5%), pollakiuria (n = 11; 28%), and hematuria and nocturia (n = 10 each; 25%). Conclusion rAd-IFNα/Syn3 was well tolerated. It demonstrated promising efficacy for patients with HG NMIBC after BCG therapy who were unable or unwilling to undergo radical cystectomy.
Oncologic outcome and morbidity for elderly rectal cancer patients compared to younger patients after preoperative chemoradiotherapy and curative surgery: A multi-institutional and case-matched control study.
Authors: Soo Yoon Sung, Jong Hoon Lee, Sung Hwan Kim
Journal: Journal of Clinical Oncology (2017)

736 Background: To elucidate the toxicity and survival outcome of neoadjuvant chemoradiotherapy (CRT) followed by curative total mesorectal excision (TME) in elderly rectal cancer patients compared to younger patients. Methods: A total of 1232 rectal cancer patients who received neoadjuvant CRT and curative surgery were collected from 7 tertiary institutions. After propensity-score matching, 310 patients of &lt; 70 years for younger arm and 310 patients of ≥ 70 years for elderly arm were identified, respectively and matched with 1:1 manner. Treatment response and toxicity, surgical outcome, recurrence, and survival were assessed and compared between two arms. Results: The two younger (&lt; 70 years) and elderly (≥ 70 years) arms were well-matched and had similar baseline characteristics. Median ages were 58 years for younger arm and 74 years for elderly arm, respectively. Pathologic complete response rates were not significantly different between younger arm and elderly arm (17.1% vs. 14.8%, P = 0.443). The 5-year recurrence-free survival (70.0% vs. 69.8%, P = 0.773) and overall survival (79.5% vs. 82.9%, P = 0.270) rates were not significantly different between two arms. Adjuvant chemotherapy after surgery was less frequently delivered to elderly arm than younger arm (69.0% vs. 83.9%, P = 0.773). Grade 3 or higher acute hematologic toxicity was observed more frequently in elderly arm than in younger arm (9.0% vs. 16.1%, P = 0.008 ), but late complication was not significantly increased in elderly arm (2.6% vs. 4.5%, P = 0.193). Conclusions: Despite an increased acute toxicity, elderly rectal cancer patients with good performance status would have equivalent tumor response and recurrence-free survival compared to younger patients.
Interim FDG-PET imaging during neoadjuvant chemoradiotherapy for esophageal cancer: Correlation with pathologic response.
Authors: Daniel Tandberg, Julian C. Hong, Yunfeng Cui, Brad Ackerson, Brian G. Czito, Christopher Willett, Manisha Palta
Journal: Journal of Clinical Oncology (2017)

175 Background: In this prospective study we evaluated whether changes in metabolic tumor parameters on interim flurodeoxyglucose positron emission tomography (FDG-PET) performed during neoadjuvant chemoradiotherapy (CRT) for esophageal cancer correlates with histopathologic tumor response. Methods: From February 2012 to February 2016, 60 patients with esophageal cancer underwent PET scans before therapy and after 30-36 Gy. Patients who underwent surgery after carboplatin/paclitaxel CRT were eligible for the current analysis. PET metrics of the primary site including maximum standardized uptake value (SUVmax), SUV mean, metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were extracted from the pre-treatment and interim PET based on a manual contour and SUV 2.5 threshold. Patients were called histopathologic responders if they had a complete or near complete tumor response based on the modified Ryan scheme. Relative changes in PET metrics between pre-treatment and interim PET were compared between histopathologic responders and non-responders using the Mann-Whitney test and binary logistic regression. Results: Twenty-six patients were included in the analysis. Adenocarcinoma was the most common histology (n = 23). Eleven patients (42%) had a complete or near complete pathologic response to CRT (histopathologic responders). Changes in PET metrics from pre-treatment to interim PET based on the manual contour were not significantly different between responding and nonresponding tumors. The relative reduction of SUVmax (Mean ± SD) was 38.2% ± 28.4% for histopathologic responders and 27.9% ± 31.4% for non-responders. The relative reduction in MTV, SUV mean and TLG was 36.1% ± 26.2%, 23.5% ± 21.3%, and 49.3% ± 28.3% for histopathologic responders and 28.6% ± 32.0%, 11.8% ± 19.1%, and 33.1% ± 38.5% for histopathologic non-responders, respectively. When analyzed based on the SUV 2.5 threshold there continued to be no significant difference in PET metrics. Conclusions: In this pilot study we observed changes in metabolic tumor parameters on PET performed during CRT for esophageal cancer. However, these changes did not predict for histopathologic responders.
Phase I/II study of stereotactic body radiation therapy (SBRT) to metastatic lesions in the liver or lung in combination with monoclonal antibody to OX40 in patients with progressive metastatic breast cancer (mBC) after systemic therapy.
Authors: Marka Crittenden, Alison Katherine Conlin, Nicole Moxon, Brendan D. Curti
Journal: Journal of Clinical Oncology (2015)

TPS3103 Background: Focal radiation mediates tumor regression not only through direct cell killing, but also by influencing adaptive immune responses. We and others have investigated pre-clinical murine tumor models using the combination of high dose per fraction radiation (SBRT) given in conjunction with T-cell checkpoint and co-stimulatory molecules. For instance, in established 3LL tumor in C57BL/6 mice, the combination of radiation (3 doses of 20 Gy over 10 days) followed by an agonistic OX40 antibody administered within 24 hours of the last dose of radiation cured 60% of mice. There were no cures using radiation or OX40 alone. The combination increased the percent of activated CD8+CD25+ T cell infiltrating the tumor and tumor-draining lymph nodes. We designed a translational study for patients with progressive metastatic breast cancer after systemic therapy. Methods: Patients with mBC, at least one liver or lung metastatic site amenable to SBRT and at least one other metastatic site that is evaluable are eligible. Patients with hormone receptor positive mBC must have received one prior anti-hormonal therapy and have progressed. Patients with hormone receptor negative mBC must have received at least one prior chemotherapy regimen. SBRT will be administered in consecutive cohorts of 3-6 patients at doses of 15 Gy x 1, 20 Gy x 1 and 20 Gy x 2 with the first dose on day 1 of anti-OX40. Anti-OX40 is administered at a dose of 0.4 mg/kg IV on days 1, 3 and 5 of a single treatment cycle. Patients are accruing to the 20Gy x 2 radiation dose presently. The primary objective is to determine the maximum tolerated dose of SBRT administered in combination with anti-OX40. Secondary objectives include response of radiated and non-irradiated tumor sites, the influence of anti –OX40 on circulating CD4+ and CD8+ T cells and the proliferation of and activity of effector and memory T cells. Exploratory studies of serum markers of cell lysis, immunogenicity and T-cell responses to breast cancer antigens are also planned. Clinical trial information: NCT01642290.
A pilot study of direct care nurse (DCN) education to improve adherence and knowledge of erlotinib in patients with non-small cell lung cancer.
Authors: Joan Vern Lucca, Catherine L. Hooper, Jean Boucher, Lillian Vitale Pedulla, Donna Lynn Berry, J Paul Marcoux
Journal: Journal of Clinical Oncology (2012)

e19637 Background: Adherence for oral anticancer agents is a major concern for patients in the ambulatory setting. Adherence rates for oral medication regimens are associated with proper knowledge and monitoring for adverse side effects including symptom management. To improve patient-reported adherence we studied feasibility of a DCN educational intervention to enhance participant knowledge and adherence to erlotinib while monitoring for side effects. Methods: A prospective, pilot study with 30 NSCLC patients was conducted. The study included a DCN structured education session utilizing an adapted educational tool (MOATT) from the Multinational Association of Supportive Care in Cancer (MASCC); followed within 72 hours by a DCN phone call to assess patient learning, adherence, and adverse side effects. Primary endpoints included participant-reported Knowledge Rating Scale (KRS) scores and adherence behaviors measured by the Morisky Medication Adherence Scale (MMAS-8). Adverse side effects and feasibility data were analyzed for each DCN/patient encounter. Results: MMAS-8 adherence scores indicated medium (n=11) to high (n=14) adherence rates and high KRS scores (mean 8.9, range of 7.5-10). Mean age of patients was 67 years (range 45-84 years), majority were female (81%), with race/ethnicity as Caucasian 80%, Asian 10%, and Black 10%. Mean number of erlotinib adverse events was 2.48 per patient and 22% reported 4 or more side effects. Patients contacted DCN 60 times between start and end of protocol. Feasibility included 90% (n=27/30) completing the protocol, mean time 30 minutes to administer educational session and 14 minutes for DCN 72-hour follow-up phone call. Documentation of visits indicated nurse education and follow-up, including monitoring side effects, provided valued supportive care. Conclusions: Data supports the need for and feasibilty of a nurse-led structured protocol to enhance adherence, knowledge, and symptom management. Further study of this education/monitoring intervention for patients initiating oral anticancer agents in the ambulatory setting is recommended.
Prioritizing Functional Capacity as a Principal End Point for Therapies Oriented to Older Adults With Cardiovascular Disease: A Scientific Statement for Healthcare Professionals From the American Heart Association
Authors: Daniel E. Forman, Ross Arena, Rebecca Boxer, Mary A. Dolansky, Janice J. Eng, Jerome L. Fleg, Mark Haykowsky, Arshad Jahangir, Leonard A. Kaminsky, Dalane W. Kitzman, Eldrin F. Lewis, Jonathan Myers, Gordon R. Reeves, Win-Kuang Shen
Journal: Circulation (2017)

Adults are living longer, and cardiovascular disease is endemic in the growing population of older adults who are surviving into old age. Functional capacity is a key metric in this population, both for the perspective it provides on aggregate health and as a vital goal of care. Whereas cardiorespiratory function has long been applied by cardiologists as a measure of function that depended primarily on cardiac physiology, multiple other factors also contribute, usually with increasing bearing as age advances. Comorbidity, inflammation, mitochondrial metabolism, cognition, balance, and sleep are among the constellation of factors that bear on cardiorespiratory function and that become intricately entwined with cardiovascular health in old age. This statement reviews the essential physiology underlying functional capacity on systemic, organ, and cellular levels, as well as critical clinical skills to measure multiple realms of function (eg, aerobic, strength, balance, and even cognition) that are particularly relevant for older patients. Clinical therapeutic perspectives and patient perspectives are enumerated to clarify challenges and opportunities across the caregiving spectrum, including patients who are hospitalized, those managed in routine office settings, and those in skilled nursing facilities. Overall, this scientific statement provides practical recommendations and vital conceptual insights.
NOTCH1 as a potential prognostic biomarker for anti-VEGF therapy in patients with metastatic colorectal cancer.
Authors: Tadeu Ferreira Paiva, Alexandre Andre Balieiro Anastacio da Costa, Flavio Augusto Ismael Pinto, Victor Hugo Fonseca Jesus, Raul A. Marques, Patricia Peresi, Mariana Petaccia Macedo, Ludmilla T. D. Chinen, Benedito Mauro Rossi, Maria D. Begnami, Vladmir C. Lima
Journal: Journal of Clinical Oncology (2013)

11038 Background: There are no validated biomarkers for clinical response or survival benefit in patients treated with bevacizumab (Bv) in advanced metastatic colorectal cancer (mCRC). The aim of this study was to evaluate the predictive value of putative biomarkers in mCRC. Methods: One hundred and five mCRC patients who received Bv combined with FOLFOX or FOLFIRI were retrospectively evaluated for clinical and pathological characteristics. VEGFR1, VEGFR2, VEGFR3, PlGF, DLL4 and NOTCH1 expression were assessed by immunohistochemistry on formalin-fixed, paraffin-embedded neoplastic tissue of either primary or metastatic tissue in a tissue microarray. High levels of expression were defined as less than or equal to or more than the median. Survival curves were calculated by the Kaplan-Meier method and compared by the log-rank test. For multivariate analysis the Cox proportional hazards model was used. Results: Grade 1 or 2 (p=0.01), non-mucin-producing histology (p=0.04) and presence of liver metastasis (p=0.001) were associated with a higher response rate. There was no difference between the expression of markers and the response rate. ECOG 0 or 1 (p=0.002), grade 1 or 2 (p=0.02), liver metastasis (p=0.003), no lymph node metastasis (p=0.01) no peritoneal metastasis (p=0.02) and resection of metastasis (p&lt;0.001) were correlated with higher progression-free survival (PFS). There was also a strong correlation between ECOG 0 or 1 (p=0.001), grade 1 or 2 (p=0.006), no lymph node metastasis (p=0.004), liver metastasis (p&lt;0.001) and resection of metastasis (p&lt;0.0001) with better overall survival. There was a trend between high expression of NOTCH1 (p=0.06) and worst PFS.High expression of VEGFR2 (p=0.07) was slightly associated with a better overall survival, while high expression of NOTCH1 was associated with a worse overall survival (p=0.01). Using multivariate analysis, NOTCH1 proved to be an independent variable for adverse overall survival (HR 2.01, IC 1.07 – 3.77, p=0.02). Conclusions: High NOTCH1 expression assessed by immunohistochemistry is capable of predicting poor survival in advanced colorectal cancer patients treated with bevacizumab.
Evaluating the impact of early versus late inpatient palliative care consultation for cancer patients.
Authors: Brian Cassel, Patrick J. Coyne, Nevena Skoro, Kathleen Kerr, Egidio Del Fabbro
Journal: Journal of Clinical Oncology (2013)

6638 Background: Access to specialist palliative care (hospital-based or hospice) is a recognized measure of quality in cancer care. Most cancer centers do have palliative care consult services, although the availability of a comprehensive program that includes a palliative care unit and outpatient clinic (Hui 2010) is inconsistent. A simultaneous integrated model of palliative care that facilitates earlier access to a specialized palliative care team may improve clinical outcomes. Palliative care programs should measure the access, timing and impact of their clinical service. Methods: Hospital claims data were linked to Social Security Death Index (SSDI) data from the US Department of Commerce. 3,128 adult cancer patients died between January 2009 and July 2011 and had contact with our inpatient palliative care team in their last six months of life. We determined whether IPC earlier than 1 month prior to death had an impact on hospitalizations, in-hospital mortality and referral to hospice. Results: 27.5% of cancer decedents accessed IPC, median of 22 days before death. 13.2% were discharged to hospice, median of 13 days before death. Patients with IPC earlier than 1 month until death were more likely to have hospice and fewer in-hospital deaths but there was no association between early IPC and a 30-day mortality admission. Conclusions: Palliative care services are accessed by a minority of patients and typically in the last 2-3 weeks of life. Although in-hospital deaths were reduced by earlier palliative care consultation, 30 day mortality did not improve. Hospitals may need to implement other strategies including early integration of outpatient palliative care among cancer patients, to achieve an impact on 30-day mortality admissions. [Table: see text]
Phase I dose-escalation study of pasireotide LAR in patients with advanced neuroendocrine tumors.
Authors: Alexandria T. Phan, Edward M. Wolin, Jennifer A. Chan, Jerry M. Huang, Michelle Hudson, Gareth Hughes, Guoxiang Shen, Jonathan R. Strosberg
Journal: Journal of Clinical Oncology (2013)

e15126 Background: Somastatin analogs (SSA), including octreotide and lanreotide, bind predominantly to somatostatin receptor (SSTR) 2 and form the foundation of treatment for symptomatic neuroendocrine tumors (NET). Pasireotide, a novel SSA with a broad binding affinity (SSTR 1-3 and 5), is being explored for treatment of NET. A phase 1 dose-escalation study (NCT01364415) of pasireotide long-acting release (LAR; starting dose of 80 mg) was designed to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) and to characterize safety, tolerability, pharmacokinetics, and efficacy in pts with advanced NET. Methods: Pts with advanced, well- or moderately differentiated NET received pasireotide LAR beginning at a dose of 80 mg q28d. Successive cohorts will receive doses (up to 220 mg) guided by a Bayesian logistic regression model until MTD/RP2D is reached. Results: To date, 15 pts have been treated at 80 mg (n=6) and 120 mg (n=9). Median age is 59 (44-76) years. Primary tumor sites include small intestine (40%), pancreas (20%), and lung (13.3%). All pts received prior antineoplastic therapy; 93% received prior SSA. Median number of cycles of pasireotide was 6.68 (2-14) (1 cycle=28 days). 10 (67%) pts remain on treatment: 3 on 80 mg and 7 on 120 mg. 5 (33%) have discontinued (disease progression, 2 pts; withdrew consent, 2 pts; adverse event [AE], 1 pt). Median plasma concentrations of pasireotide increased with dose. No dose-limiting toxicities have been reported. Most frequent AEs were similar in both dose groups and included hyperglycemia (87%), diarrhea (53%), abdominal pain (47%), nausea (40%), anemia (33%), and fatigue (33%). Most AEs were mild/moderate. 2 pts (1 in each group) had grade 3 hyperglycemia. 4 (27%) and 2 (13%) pts had HbA 1C increase from &lt;6.5% at baseline to 6.5-&lt;8% and ≥8%, respectively. 13 (87%) pts had radiographically stable disease as best response. More pts at 120 mg (50%) vs 80 mg (33%) achieved ≥50% reduction in chromogranin A. Conclusions: Pasireotide LAR up to 120 mg appears to be well tolerated in patients with advanced NET. The study is ongoing. Pasireotide represents a promising therapy for pts with NET. Clinical trial information: NCT01364415.
A nomogram for testosterone recovery following combined androgen deprivation therapy and radiation therapy for prostate cancer.
Authors: Daphna Spiegel, Julian C. Hong, W. Robert Lee, Joseph Kamel Salama
Journal: Journal of Clinical Oncology (2017)

67 Background: Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is a frequently used localized prostate cancer (PC) treatment. Testosterone recovery (TR) after combined ADT-RT is not well-characterized. We studied TR in men who received RT and either short-term (ST) ADT or long-term (LT) ADT with LHRH agonists. Methods: We identified consecutive localized PC patients treated with ADT-RT at the Durham VA Medical Center (DVAMC) from 1/2011-10/2016. All patients had a documented baseline testosterone (T) level. Individual patient records were reviewed. TR was defined as time from last ADT injection to T normalization ( &gt; 240 ng/dL). The Kaplan-Meier method was used to estimate time to TR. Cox proportional hazards models were generated to identify TR predictors with a nomogram built based on a parsimonious multivariate model. Results: 252 patients were identified. Median follow-up was 26.7 months. Median age was 65. Prior to treatment, 69% had a normal baseline T. 67% were treated with STADT, median duration 6 months. 33% were treated with LTADT, median duration 18 months. Median time for TR was 22.6 months for all patients (19.5 months for STADT and 25.6 months for LTADT). At 1 and 2 years post ADT, estimated TR was 13% and 53% (17% and 57% for STADT and 3% and 42% for LTADT). 2-year biochemical control was 99.2% and 97.6% for STADT and LTADT, respectively; 98.9% and 98.6% for those with and without TR, respectively. On multivariate analysis, higher pre-treatment T (HR = 1.004 95% CI 1.003-1.006, p &lt; 0.001), use of STADT (HR = 2.48 95% CI 1.45-4.25, p = 0.001), and lower BMI (HR = 0.95 95% CI 0.91-0.98, p = 0.001) were associated with shorter time to TR. White race was a negative TR predictor (HR = 0.65 95% CI 0.43-0.9992, p = 0.049). Age, smoking, and Charlson Comorbidity Index were not significant independent TR predictors. A nomogram was generated to predict probability of TR at 1, 2, and 3 years. Conclusions: In this VA population of localized PC patients treated from 2011-2016, TR following the use of ADT-RT was variable. Using pre-treatment T levels, ADT duration, BMI, and race, a predictive nomogram can estimate the likelihood of TR.