tbuckley/cabot-search huggingface dataset:
Use of low-dose cyclophosphaminde followed by low-dose tumoral radiation, intratumoral poly-ICLC combined with local-regional therapy, followed by systemic immune boosting with intramuscular poly-ICLC in patients with cancers of the liver.
Authors: Andrew N de la Torre, Ismael Castaneda, Sohail Contractor, Andres M. Salazar
Journal: Journal of Clinical Oncology (2015)

327 Background: Cancers in the liver are susceptible immune evasion due to the liver’s role in self-tolerance. Eliminating liver cancers may require multiple steps to reduce tumor tolerance, increase expression of tumor-associated antigens, and turn on immunity against such tumor antigens. Methods: Phase I-II trial to 1) reduce tumor tolerance with oral cyclophosphamide 50 mg/day x 21 days, 2) increase tumor antigen visibility with low dose radiation (2.5 Gy x 3 days), 3) induce a “danger” response with intra-tumoral injection of the TLR3 agonist poly-ICLC (1mg) and concurrent hepatic artery embolization and 4) enhance immunity with intramuscular poly-ICLC (20 mcg/kg). Results: From 2/17/2007 to 7/27/12, 25 patients were enrolled. Cancers were 17 hepatoma (HCC), 3 metastatic pancreas (mPANC), 2 metastatic neuroendocrine (mNEURO), and 2 cholangiocarcinoma (CC). Patients were not liver transplant eligible at enrollment. Patient 1 with cirrhosis died after embolization of a 13 cm HCC. Patients 2-25 had no adverse events (AE) greater than grade 2. The most common AEs were fatigue (13), anorexia (7), injection site rash (7), fever (6), and diarrhea (3). Of 17 HCC patients, the mean survival was 737 days. Two patients were downstaged and underwent liver transplant. One patient was transplanted after 203 days and is still alive. The second patient was transplanted after 1433 days, but died 10 days following transplant. We had one patient who presented with multiple large HCCs and portal vein invasion surviving 984 days and another patient with multiple large HCCs still alive after 2451 days. Both patients with mNEURO tumors are still alive after 1905 and 736 days. All patients with CC and mPANC cancer died. Conclusions: This approach is well tolerated. Caution should be used with embolization of large tumors. Although the overall survival was just over two years, several patients with advanced HCC and mNEURO tumors lived beyond our expectations. Further investigation is needed to optimize this method and identify patients who will benefit most from this immunotherapeutic approach. Clinical trial information: NCT00553683.
Information sources cancer patients use to find out about phase I and II clinical trials: An exploratory pilot feasibility study
Authors: D. Casa, B. F. Piper, M. J. Borad, J. Hepworth, S. P. Anthony, E. Campbell, J. Ingold, G. S. Jameson, R. K. Ramanathan, D. D. Von Hoff
Journal: Journal of Clinical Oncology (2008)

20731 Background: Accrual to trials remains a challenge where less than 5% of adult cancer patients participate. This low accrual rate is even more problematic for Phase I/II trials as it can delay development of promising new targeted forms of therapies. Few studies have investigated sources of information (SOI) cancer patients use to find out about Phase I/II trials, and none have examined possible demographic, disease and treatment-related correlates/predictors that may be SOI-related. Methods: This was an exploratory pilot feasibility study. Eligibility criteria: All patients enrolled in/considering enrollment in a Phase I/II trial at one large southwestern academic/community-based cancer research setting. A 47-item patient-completed survey was used. Data were entered into Excel and transferred to SPSS for descriptive (means, frequencies, percentages, SD, ranges), correlational and inferential exploratory statistical analyses (Chi Square, t-test, ANOVA, hierarchical and logistic regression). Results: The average patient (n=50) was a 60yrs old, married college-educated white non-Hispanic with advanced cancer. Most frequently identified SOI (used, helpful, valued, recommended) were the patient’s medical oncologist, research oncologist/staff, and internet websites. Correlational/predictive exploratory analyses of demographic (age, gender, education, income, computer/internet access, type of health insurance); disease (date diagnosed [Dx’d], type of Dx, more than one Dx, cancer stage, comorbidities, performance status, disease stage knowledge, family members Dx’d), and treatment variables (current trial enrollment, trial phase knowledge, past trial participation and phase knowledge, number of past cancer therapies and number of second opinion consultations) are in progress. Conclusions: Study outcomes will be useful to investigators interested in improving trial recruitment strategies; standardizing how SOI data are collected; and discussing how standardization can lead to a database to be used in future studies to identify how SOI and referrals affect accruals, change overtime, and affect development/evaluation of recruitment strategies. No significant financial relationships to disclose.
Cancer Therapy: Low‐Dose Prostate Cancer Brachytherapy with Radioactive Palladium–Gold Nanoparticles (Adv. Healthcare Mater. 4/2017)
Authors: Myriam Laprise‐Pelletier, Jean Lagueux, Marie‐France Côté, Thomas LaGrange, Marc‐André Fortin
Journal: Advanced Healthcare Materials (2017)

Prostate cancer is often treated by internal radiotherapy (brachytherapy), by which tens of radioactive implants made of massive metal « seeds » are inserted in the diseased tissue. Article number 1601120 by Marc-André Fortin and co-workers, reports on a new technology based on the injection of radioactive gold nanoparticles. The nanoparticles diffuse into the tumour, where they progressively deliver a radiotherapeutic dose more precisely and with fewer potential side-effects.
Phase II trial of high-dose bolus (HDB) IL-2 in patients with metastatic melanoma (MM) who haveprogressed after biochemotherapy (BCT): Updated results
Authors: S. S. Agarwala, A. Tarhini, W. Gooding, C. Cai, J. M. Kirkwood, L. L. Stover
Journal: Journal of Clinical Oncology (2005)

7548 Background: BCT comprising multiagent chemotherapy, continuous infusion IL-2 and IFN-alfa has produced high response rates (40–50%) in phase II studies, but recent randomized trials have failed to show a superiority over CT alone. HDB IL-2 produces long-term remissions in 6–10% of previously untreated patients with MM and utilizes higher doses of IL-2 than in BCT. The activity of HDB IL-2 after BCT failure has not been formally evaluated. Methods: A phase II trial of HDB IL-2 for patients who had progressed following BCT was conducted at the University of Pittsburgh. Eligible patients had measurable disease, PS 0–1 and had progressed on or after BCT (cisplatin, vinblastine, dacarbazine, IL-2, 9 MU/m2/day X 4 days, and IFN-alfa 2b). HDB IL-2 was administered at 600,000 U/kg per dose, for a maximum of 14 doses per cycle with a one-week rest period between cycles. Stable or responding patients were offered an additional course of therapy after 6–8 weeks. Treatment was conducted on an in-patient oncology unit with trained personnel. Results: 26 patients (12 male, 14 female) age 28–70 (median 45) years have been treated. All but 3 patients received at least two cycles (one course) of HDB IL-2; 10 patients received a second course of therapy. The median number of doses administered was 9 (range 6–14) during cycle 1 and 7 (range 2–12) during cycle 2. Disease stage was AJCC Mla (5) Mlb (5) and Mlc (16). Grade 3 toxicities included hyperbilirubinemia (10), thrombocytopenia (6), tachycardia (5), hypotension (4), oliguria (3), diarrhea (1), infection (2) and neurologic (2). Grade 4 toxicities included thrombocytopenia (1) and hyperbilirubinemia (1). Overall response rate was 19% (4 complete, 1asting 4, 4, 15+ and 24+ months, 1 partial, lasting 3 months). Seven patients (27%) had SD lasting 1–3 months, but all eventually progressed. All 4 complete responders were AJCC Stage Mla. At a median follow-up of 7 months median survival is 42.3 weeks (95% CI 18.3–66 weeks). Conclusions: HDB IL-2 can produce durable remission in patients with MM who progress on BCT. In this small trial, response rates were not dissimilar from those obtained in previously untreated patients. No significant financial relationships to disclose.
Constitutive genetic instability in patients with multiple, primary non-small cell lung cancers
Authors: B. J. Park, I. Orlow, U. Mujumdar, P. K. Ginex, B. A. Clas, M. G. Kris, V. W. Rusch, C. B. Begg, M. Berwick
Journal: Journal of Clinical Oncology (2005)

7041 Background: Although tobacco is the major etiologic factor in non-small cell lung cancer (NSCLC), there is no way to predict which individuals have the greatest risk. Previous studies have suggested that constitutive DNA damage may modulate individual susceptibility to develop NSCLC. To test this, we hypothesized that, compared to patients with a single primary NSCLC, individuals with multiple primary NSCLCs would demonstrate greater constituative genetic instability. Methods: We performed a case-control study measuring constitutive genetic instability in human peripheral blood lymphocytes by the Comet assay in patients with multiple versus a single primary NSCLCs. Groups were frequency matched by age at first diagnosis (5-year age groups), gender, and time since diagnosis. Peripheral blood and risk factor questionnaires were collected. Tail moment (TM) and tail intensity (TI) in electrophoresed DNA were measured as parameters of constitutive DNA damage in each patient. Univariate and multivariate analyses were performed to detect differences between the two groups. The median TM and TI values were used to calculate odds ratio (OR) estimates using logistic regression. Results: The Comet assay was performed on lymphocytes from 58 patients with multiple primaries and 44 single primary controls. TM was significantly increased in patients with multiple primaries (1.34 ± 0.98 versus 0.67 ± 0.40, p<0.001), as was TI (1.19 ± 0.55 versus 0.81 ± 0.25, p<0.001). When adjusted for age, gender, prior treatment and smoking status, these differences remained. When data were dichotomized at the median value for DNA damage in single primary subjects, an increased estimated relative risk of multiple NSCLCs was associated with constitutive genetic instability (OR 3.5; 95% CI 1.5–8.1). After adjusting for age, gender, prior treatment and smoking status, this elevated relative risk remained important (OR 3.0; 95% CI 1.2–7.4). Conclusions: Constitutive genetic instability measured by the Comet assay is associated with an increased estimated relative risk for development of multiple primary tumors in individuals with NSCLC. Supported by grants from The Society of Memorial Sloan-Kettering and Steps for Breath. No significant financial relationships to disclose.
Characteristics of African Americans (AAs) treated with sipuleucel-T (sip-T): Comparison of clinical trial and real-world experience.
Authors: Ronald F. Tutrone, Chiledum Ahaghotu, Andrew J. Armstrong, Celestia S. Higano, Matthew R. Cooperberg, Laurence H. Belkoff, Carl A. Olsson, Sanjay Goel, Robert Claude Tyler, Jennifer Susan LIll, Todd E. Gray, Candice McCoy, A. Oliver Sartor
Journal: Journal of Clinical Oncology (2015)

272 Background: AA men are underrepresented in randomized clinical trials (RCTs) for prostate cancer, despite an almost 2-fold greater incidence in AA vs Caucasian populations. Sip-T is an autologous cellular immunotherapy approved by the FDA and EMA for the treatment of certain patients (pts) with asymptomatic or minimally symptomatic metastatic castration-resistant prostate cancer. AA enrollment in three sip-T phase 3 RCTs was 5.8% (n=43). While no definitive conclusions were drawn, median overall survival (OS) suggested AAs benefit from sip-T. PROCEED, an ongoing phase 4 registry, expanded efforts to increase AA enrollment to better characterize this population and the safety, product parameters (PP), and OS of AAs treated with sip-T. Methods: PROCEED enrolled 1973 pts treated with commercial sip-T within 6 months of registration. Efforts, such as selecting racially diverse sites and highlighting AA enrollment in PROCEED communications and investigator meetings, were used to boost AA enrollment. Baseline Gleason score, Eastern Cooperative Oncology Group performance status (ECOG), prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were compared between RCTs and PROCEED. Safety and survival analyses are ongoing. Results: PROCEED AA enrollment was 11.7% vs 7.1% US RCT nonwhite enrollment rate and approaches the US AA population of 13.7%. Baseline AA pt characteristics were: lower median PSA and ALP levels in PROCEED vs RCTs, higher ECOG &gt;0 in PROCEED vs RCTs, and higher Gleason score ≥8 in PROCEED vs RCTs (Table). Conclusions: Efforts to boost AA enrollment in PROCEED to a proportion comparable to the US AA population succeeded. The lower baseline PSA of AAs in PROCEED is similar to the PSA observed in the entire PROCEED population. Safety, PP, and OS will be reported with longer follow-up. Clinical trial information: NCT01306890. [Table: see text]
Does radiation therapy increase late cardiac death in patients with esophageal cancer?
Authors: Chi Lin, Kyle A. Denniston
Journal: Journal of Clinical Oncology (2013)

90 Background: The objective of this study was to evaluate the effect of radiation therapy (RT) on late cardiac death in patients with esophageal cancer. Methods: A total of 35,618 patients diagnosed with esophageal squamous cell carcinoma (SCC) or adenocarcinoma (ADE) between 1973 and 2008 were identified from the SEER database. After excluding records with missing data, 24983 patients remained. Patients who survived ≥ 5 years (2075) were identified for this analysis. Examined risk factors for cardiac death include age (≤55/56-65/66-75/&gt;75), gender, race (white/non-white), stage (local/regional/distant), histology (SCC/ADE), esophageal subsite (&lt;18cm/18-24cm/25-32cm/33-40cm), diagnosis year (1973-1983/1984-1993/1994-2003), and treatment with surgery or RT. Time to cardiac death was evaluated using the Kaplan-Meier method. A multivariate logistic regression model with backward elimination and the Cox Proportional Hazards model were used to evaluate risk factors for cardiac death. Results: Patients who received RT tended to be younger, white, diagnosed more recently, have more advanced disease, SCC histology and not undergo surgery. RT group had a higher risk of cardiac death than no-RT group (Log-Rank p &lt; 0.0001). Median time to cardiac death in RT group was 251 months (95% CI 223-367) and was not reached in no-RT group. The probability of cardiac death increased with age and decreased with diagnosis year. This trend was more pronounced in RT group. Multivariate analysis found RT to be associated with higher probability of cardiac death (OR 1.45, 95% CI 1.10-1.93), after adjusting for age and diagnosis year. Gender, race, histology, stage, esophageal subsite and surgery status were not associated with cardiac death. After adjusting for age, Cox model showed that patients who received RT were more likely to die of cardiac causes than those who did not receive RT (HR 1.91, 95% CI 1.47-2.47). Diagnosis year was not a risk factor in the Cox model. Conclusions: Patients with esophageal cancer who received RT and survived ≥ 5 years had a higher risk of cardiac death than those who did not receive RT. Further study of cardiac outcome in long term survivors of esophageal cancer treated with RT, and accounting for comorbidity, is warranted.
A meta-anlysis for pediatric leukemia treatment: bone marrow or cord blood transplantation?
Authors: X. Shixia
Journal: Journal of Clinical Oncology (2008)

10043 Background: To observe the therapeutic efficacy of unrelated donor umbilical cord blood transplantation(UCBT) and unrelated donor bone marrow transplantation(UBMT) in pediatric Leukemia. Methods: We electronically searched the Cochrane Central Register of Controlled Trials (CENTRAL),MEDLINE,[database],[Database] and critically appraised all relevant articles(1999- 2007). Comparative studies were carried out on clinical therapeutic effect of UCBT and UBMT with research on stem cells engraftment, complications, earlier mortality, and survival rate. We performed a meta-analysis using Review Manager 4.2 software and adopted funnel plot regression to assess the publication bias. Results: We obtained 292 records. 6 trials totaling 668 patients have been assessed. Pooled comparisons of studies of UCBT and UBMT in children found that the incidence of engraftment failure and earlier transplantation-related mortality were high with UCBT because of its delay of Hematologic recovery, but cytomegalovirus infection didn’t increase obviously. There was no difference in long disease-free survival rate between UCBT and UBMT due to the decrease of chronic graft-versus-host disease (GVHD). Conclusions: Our meta-analysis confirmed that UCBT in children had consistently equivalent survival outcomes compared with UBMT. The data showed that UCBT was also an effective way to treat children with leukemia. No significant financial relationships to disclose.
Accelerated fraction radiotherapy with concomitant capecitabine as neoadjuvant therapy of borderline resectable pancreatic cancer.
Authors: Samhita Chakraborty, Todd W. Bauer, Monica M Morris, Erin Yarde, J Thomas Parsons, Reid B Adams, Hanna Kelly Sanoff
Journal: Journal of Clinical Oncology (2012)

329 Background: Surgical therapy remains the only curative modality for pancreatic cancer, though survival remains quite poor even for patients with resected early stage disease. Better (neo) adjuvant therapies are needed to improve resectability rates for patients with borderline resectable pancreatic cancer and to prevent recurrence following resection. We undertook this pilot study to determine the safety of accelerated fraction radiotherapy (AFRT) with capecitabine in such patients. Methods: Eligible patients have histologically confirmed borderline resectable adenocarcinoma of the pancreas as defined by the MD Anderson categories of vascular involvement, indeterminate metastatic disease, borderline performance status; normal organ function; and no prior therapy for pancreatic cancer. Radiation is given as external beam radiation therapy to a dose of 50 Gy delivered in 20, 2.5 Gy fractions Mon-Fri using IMRT. If insurance denied IMRT, 3D conformal techniques with daily image guidance is permitted. Capecitabine is delivered as 825mg/m 2 BID on radiation days. The primary outcome is to determine the frequency of treatment-related adverse events (AE). Planned enrollment is 40 pts. Results: 10 pts have enrolled to date. 8/10 received IMRT. This regimen has been exceedingly tolerable. Lymphopenia is the most common AE (n=10), grade 3-4 n=6. Other common toxicities were hyponatremia (n=6), fatigue (n=5). Grade 3 AE occurred in 8 pts, grade 4 in 3 patients. One pt had hemorrhage from a radiation induced gastric ulcer complicated by an MI. 5/10 pts had stable disease and were resected and 4/5 had an R0 resection. In the remaining 5/10 patients, disease progressed outside the pancreas and they are receiving palliative therapy. Conclusions: The combination of AFRT and capecitabine was well tolerated. Xenograft models derived from these patients’ tumors are being used to study molecular mechanisms of treatment resistance that could be targeted in a follow up phase II study building on this platform.
Concurrent chemoradiotherapy using high-dose rate intracavitary brachytherapy for locally advanced cervical cancer (stage III or IVA and pelvic lymph node metastasis)
Authors: N. Lee, E. Song, J. Kwak, H. K. Lee, J. Kim, C. Yim
Journal: Journal of Clinical Oncology (2008)

16582 Background: Cisplatin-containing concurrent chemoradiotherapy (CCRT) with brachytherapy is the standard treatment for bulky (above stage II) and pelvic lymph node positive cervical cancer. In this study, we evaluated the efficacy and the feasibility for CCRT using high-dose-rate intracavitary brachytherapy (HDR-ICRT) in the treatment of patients with locally advanced cervical cancer. Methods: A total of 33 patients with stage III or IVa and pelvic lymph node positive cervical cancer treated with CCRT using HDR- ICBT were evaluable. External beam radiotherapy (EBRT) with 45 Gy/25 fractions followed by HDR-ICBT with 28 Gy/8 fractions to point A was performed. Chemotherapy consisted of weekly cisplatin at a dose of 40 mg/m2 for 5 courses was concurrently administered with radiotherapy. Results: There were 25 (75.8%) complete responses and 8 (24.2%) partial responses. The median time to progression was 15.3 months. In the nine recurred patients, local and systemic failure rate was 9.1% and 24.2%, respectively. The 3-year overall survival rate was 59.6%. The incidence of any grade 3/4 acute adverse event was 27.3% and hematologic toxicity was the most common adverse event. There was no grade 3/4 late complications including proctitis and cystitis. Conclusions: Weekly cisplatin 40 mg/m2 concurrent with EBRT followed by HDR-ICBT is feasible and efficacious for patients with locally advanced cervical cancer. No significant financial relationships to disclose.
Using IT solutions to empower your patients and improve quality and satisfaction scores.
Authors: Gerard Colman, Todd L Foster
Journal: Journal of Clinical Oncology (2013)

249 Background: Provider organizations are being bombarded from every direction with demands to better patient experience, engage patients, manage populations, implement or enhance implementations of EHRs…the list goes on. Dr. Charles Safran testified to Congress in 2004 that “patients are the most underutilized resource in the U.S. health system.” Taking this to heart, MD Anderson’s recognized their complex registration process was perceived as overwhelming and new patients were experiencing feelings of uncertainty and a lack of control. Patients translated this into poor quality of care. Patients and their caregivers needed to be engaged during this emotionally trying time. Methods: PreCare was born from the desire to use technology to place the first appointment process into the patients’ hands. PreCare is a web site that allows patients to drive the process to expedite their first appointment and track progress transparently. It gives the patients the appropriate information at the appropriate time during their first appointment process. No longer are they bombarded with all information all at once. They could not possibly process it all so vital information was missed, resulting in poor quality of care. Results: Obtaining medical records faster has increased the quality of patient care. Approximately 24% of previously diagnosed patient diseases are changed or refined from their original diagnosis. Accurate diagnosis is critical as cancer treatments become more targeted. MD Anderson has noted improvements in clinical operations, increases in patient retention, reducing dependence on staff, manual processes, print materials and phone calls. Presenters will demonstrate the self-driven tools, lessons learned and the impact of using IT such as: a 4% increase in new referrals, reduction in costs, improvements in efficiency and increased satisfaction for staff, patients and their families. A 47% reduction in patient anxiety has been demonstrated. Conclusions: The overall system utilization is well above national averages, with as high as 74% utilization in key areas. All cancer patients have very high expectations. Our patients using PreCare find their quality of care far exceeds their expectations.