tbuckley/cabot-search huggingface dataset:
Does post-operative radiotherapy (P-RXT) after radical prostatectomy (Px) improve progression-free survival (PFS) in pT3N0 prostate cancer (PC)? (EORTC 22911)
Authors: M. Bolla, H. Van Poppel, P. Van Cangh, K. Vekemans, P. Rigatti, T. De Reijke, A. Verbaeys, J.-F. Bosset, L. Collette
Journal: Journal of Clinical Oncology (2004)

4504 Background:In 1992, as radical prostatectomy was more frequently applied to clinical T1–2N0M0 prostate cancer, the EORTC has undertaken a randomized trial of immediate post-operative treatment versus wait-and-see policy, for patients with high risk factors of local relapse on pathological specimen. We present the first efficacy results of this study. Methods: Eligible patients were ≤75 years old, WHO performance status (PS) 0–1, had T0–3N0M0 PC preoperatively and ≥1 pathological risk factor of: capsule invasion, positive surgical margins, invasion of seminal vesicles. P-XRT was 60Gy conventional external radiation delivered over 6 weeks. The trial was powered to detect a hazard ratio (HR) of 0.77 with 80% power with two-sided α=0.05 with regard to clinical or biological progression-free survival. Results: 1005 pts were accrued by end 2001 (P-XRT: 503, Px: 502). Median age was 65.4 years, PS 0 in 93.8%, median pre- and post-operative PSA 12.3 and 0.2 ng/ml, respectively. All but 41pts on P-XRT were irradiated with median dose 60Gy (range: 50–74). The trial was reviewed by an IDMC in December 2003, after a median follow-up of 5 years and early disclosure of the trial results was recommended. Biochemical PFS (time to twice confirmed PSA increase over nadir or first clinical failure or death) at 5 years was 72.2% (CI: 67.7–76.8) on P-XRT and 51.8% (CI: 46.8–56.8), HR=0.52 (CI: 0.42–0.64), P<0.0001. Clinical PFS was improved from 74.8% to 83.3% at 5 years (HR=0.68, CI: 0.52–0.89, P=0.004). The incidence of loco-regional failure was significantly decreased (P<0.0001). Further follow-up is needed to assess the impact on distant metastases and overall survival. P-XRT is associated with an increased risk of immediate and late grade 1–2 side effects. Grade 3 side effect rates so far were less than 5% in both groups. Conclusions: Post-operative radiotherapy results in improved biochemical and clinical PFS. This benefit is to be weighed against the treatment side effects. Further follow-up is needed to assess the impact on overall survival. No significant financial relationships to disclose.
Drug rechallenge following drug‐induced liver injury
Authors: Christine M. Hunt, Julie I. Papay, Vid Stanulovic, Arie Regev
Journal: Hepatology (2017)

Drug-induced hepatocellular injury is identified internationally by alanine aminotransferase (ALT) levels equal to or exceeding 5× the upper limit of normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decrease by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT level of 3-5× ULN or greater. Nearly 50 drugs are associated with positive rechallenge after drug-induced liver injury (DILI): antimicrobials; and central nervous system, cardiovascular and oncology therapeutics. Drugs associated with high rates of positive rechallenge exhibit multiple risk factors: daily dose >50 mg, an increased incidence of ALT elevations in clinical trials, immunoallergic clinical injury, and mitochondrial impairment in vitro. These drug factors interact with personal genetic, immune, and metabolic factors to influence positive rechallenge rates and outcomes. Drug rechallenge following drug-induced liver injury is associated with up to 13% mortality in prospective series of all prescribed drugs. In recent oncology trials, standardized systems have enabled safer drug rechallenge with weekly liver chemistry monitoring during the high-risk period and exclusion of patients with hypersensitivity. However, high positive rechallenge rates with other innovative therapeutics suggest that caution should be taken with rechallenge of high-risk drugs.For critical medicines, drug rechallenge may be appropriate when 1) no safer alternatives are available, 2) the objective benefit exceeds the risk, and 3) patients are fully informed and consent, can adhere to follow-up, and alert providers to hepatitis symptoms. To better understand rechallenge outcomes and identify key risk factors for positive rechallenge, additional data are needed from controlled clinical trials, prospective registries, and large health care databases. (Hepatology 2017;66:646-654).
Leveraging a software application to prepare for regulatory inspection within a hematopoietic cellular therapy program.
Authors: Betsy Blunk, Jesse Jawanda, Kevin Drake, Rocky Lee Billups, Tonya Cox, Therese Dodd, Charles F. LeMaistre
Journal: Journal of Clinical Oncology (2017)

142 Background: The Sarah Cannon Blood Cancer Network (SCBCN) is comprised of seven Hematopoietic Cellular Therapy (HCT) programs. Regulations require that programs have a consistent and continuous process to identify and measure compliance to ensure standards are met. Every 3 years, programs undergo inspections by the Foundation for the Accreditation of Cellular Therapy (FACT). Historically, programs would prepare for inspections by utilizing paper documents that support and demonstrate compliance with standards. The goal of this project was to develop an electronic platform to manage the FACT inspection. COMAIBA (Compliance Management Actionable Intelligence Business Analytics) was selected as a development partner. Methods: Within our HCT programs, a thorough analysis was performed to determine the current processes by which inspections took place. The FACT assessment questionnaire was reviewed and each standard was evaluated. Quality coordinators within the programs highlighted the key documentation necessary to meet each standard. Results: In collaboration with COMAIBA, a regulatory compliance module was developed which allows the programs to electronically prepare for and manage FACT inspections. There are currently over 1600 questions within the application broken down into clinical, apheresis, marrow collection and processing facility subsections. Programs upload supporting documentation to demonstrate how they comply with each standard. From a programmatic level, administrators and key personnel can, at any time, view the preparation process via a dashboard and view the compliance measures electronically. Conclusions: This electronic solution allows quality teams to proactively prepare for inspections and keep information current and up to date on an ongoing basis. As standards evolve, the design of the COMAIBA application allows versatility in updating and maintaining compliance. COMAIBA is working to utilize this format for other regulatory and accrediting bodies i.e. CoC, UNOS. In addition, allowing the inspectors to view information electronically prior to coming onsite may enhance the inspection process and allow for a more comprehensive review.
Alternating chemoradiotherapy for nasopharyngeal cancer using cisplatin and 5-fluorouracil - A preliminary report of phase II study
Authors: N. Fuwa, T. Kodaira, K. Furutani, H. Tatibana, T. Toita, N. Shikama, M. Kano, N. Hayasi, A. Yuta
Journal: Journal of Clinical Oncology (2004)

5613 Background: Nasopharyngeal cancer (NPC) is characterized by a high frequency of distant metastasis and mucositis was a marked problem even when radiotherapy (RT) alone was performed. Considering these characteristics of NPC, alternating chemoradiotherapy (ALT-CRT) may be a useful method of treating NPC because sufficient amount of anti-tumor agents can be administered together with a low frequency of mucositis compared to concurrent chemoradiotherapy (CRT). Methods: The subjects consisted of 16 patients with stage II, 25 patients with stage III and 26 patients with stage IV . Using 6 MV photon, RT was performed at an exposure of 1.8Gy 5 times a week. That is, a total absorbed dose of 36 Gy was irradiated between the basal of skull and supraclavicular fossa. After decreasing the irradiation field, an absorbed dose of 30–34Gy was additionally given thereafter. One course of chemotherapy (CT) consisted of the administration of 5-FUdepends on document reviewat a dose of 800 mg/m2/24 h for 5 days (days 1–5) and CDDP at a dose of 50 mg/m2/24 h for 2 days (days 6–7), and a total of 3 courses of CT was performed. During the ALT-CRT, CT was performed initially; and 2–3 days after completing the CT, RT was performed for 4 weeks. Thereafter, CT and RT were performed alternately. Results: The scheduled courses of ALT-CRT were completed in 57 (87%) of 67 patients. No severe adverse effects were noted in any other patients. In these 67 patients, the overall 3-year survival rate was 93%, and the progression free survival rate was 80% (The median follow up times was 33 months). Conclusions: This method of ALT-CRT yielded higher or at least similar survival rate and lower toxicities than concurrent CRT, and we believed that this method can be used in a controlled clinical trial in the future to compare therapeutic results with those of the Intergroup 0099 Trial No significant financial relationships to disclose.
Results of a randomized, global, multi-center study of whole-brain radiation therapy (WBRT) plus veliparib or placebo in patients (pts) with brain metastases (BM) from non-small cell lung cancer (NSCLC).
Authors: Pierre Chabot, Jeong-Seon Ryu, Vera Gorbunova, Cristobal Belda, David Ball, Ebenezer A. Kio, Minesh Mehta, Katherine Papp, Qin Qin, Jane Qian, Kyle D. Holen, Vincent L. Giranda, John H. Suh
Journal: Journal of Clinical Oncology (2015)

2021 Background: Veliparib (V) is a potent, orally bioavailable PARP inhibitor that crosses the blood brain barrier. Phase 2 trials in BRCA pts as monotherapy or in unselected pts in combination with platinum-based chemotherapy have demonstrated evidence of efficacy. V plus radiation has shown promising efficacy in preclinical models and clinically in combination with WBRT. Methods: Pts were randomized 1:1:1 to WBRT plus V 50 mg BID (V50), V 200 mg BID (V200), or P BID. Treatment began within 28 days (d) of diagnosis. Pts received 30 Gray WBRT in 10 fractions. V50, V200, or P BID was self-administered starting on d 1 of WBRT and continuing until 1 d after completion. The primary endpoint was overall survival (OS). Survival was assessed at 2 month (m) intervals for 6 m then every 3 m (≥36 m). Pts who received ≥1 dose were included in the safety analyses; AEs were compared across arms using Fisher's exact test. Results: 307 pts were randomized. OS, intracranial response rate, and time to clinical or radiographic progression were not statistically significantly different between any of the V arms and the P arm. There were no differences in all grade adverse drug reactions (ADRs) across arms and a modest improvement in grade 3/4 AEs in the V arms. Conclusions: Although preclinical and early clinical data suggested that V might synergize with radiotherapy, there was no difference in multiple study endpoints between V50 or V200 and P in this setting. Safety parameters observed in the V arms were generally similar to the P arm; no new safety signals of V were identified. Clinical trial information: NCT01657799. P N=102a V50 N=103 V200 N=102 Median age, years 60 60 62 Sex, n Male 56 61 66 Graded Prognostic Assessment (GPA), n ≤2.5 91 91 92 Median OS, d (95% CI) 185 (137–251) 209 (169–264) 209 ( 138–255) Objective Response Rate, % 41.2 36.9 42.2 Median time to clinical BM progression per event review board, d (95%CI) 348 (216–NR) 286 (192–NR) 255 (204–342) Median time to radiographic BM progression per central imaging center, d (95%CI) 259 (184–NR) 226 (147–360) 224 (137–358) All ADRs, % 37 37 40 Gr 3/4 AEs, % 43 28 (p=.040) 26 (p=.012) a1 not dosed or included in the safety analysis; NR, not reached.
Induction of multidrug resistance on mRNA and on protein level by fractionated irradiation
Authors: D. Bottke, T. Wiegel, A. M. Asemissen, K. Heufelder, W. Hinkelbein, U. Keilholz
Journal: Journal of Clinical Oncology (2004)

2136 Background: Radiotherapy (RT) can induce the expression of P-glycoprotein (P-gp, gene product of the multidrug resistance [MDR] gene 1), which can lead to a broad cytostatic drug resistance. Kinetics of this expression is unknown, but possibly important for radiochemotherapy protocols. It is unknown, whether other multidrug resistance mechanisms are also affected by RT. We examined kinetics of the expression of the 3 most important MDR-associated proteins MDR1, MRP (multidrug resistance-associated protein) and LRP (lung resistance protein) in different tumor cell lines under fractionated irradiation. Methods: 4 human tumor cell lines (NSCLC [A-427], colon carcinoma [HT-29], breast cancer [MCF-7] and melanoma [SK-MEL-24] were irradiated with 5 fractions of 1,8 Gy per week to a total dose of 9, 27, 45 and 59,4 Gy. Kinetics of mRNA expression was assessed by quantitative RT-PCR, and of protein expression by flow cytometry. Results: The colon carcinoma and breast cancer cell lines showed significant and stable radiation-induced overexpression of all 3 MDR mediators on mRNA as well as on protein level beyond week 2. The NSCLC line showed stable radiation-induced overexpression only of LRP on mRNA and protein level. The melanoma cell line showed no induction of any of the three MDR proteins. Conclusions: Fractionated irradiation can induce the expression of different multidrug resistance proteins in tumor cell lines, which could lead to broad resistance against cytotoxic drugs. This finding is of potential impact for radiochemotherapy protocols. No significant financial relationships to disclose.
Infliximab: A phase II trial of the tumour necrosis factor (TNFα) monoclonal antibody in patients with advanced renal cell cancer (RCC)
Authors: N. R. Maisey, K. Hall, C. Lee, E. Timotheadou, R. Ahern, T. Eisen, M. Gore
Journal: Journal of Clinical Oncology (2004)

4514 Background:Standard treatments for advanced RCC include interferon-α (IFα) and interleukin-2 (IL2) with response rates of 15%. Several small peptides are over-expressed in RCC including TNFα. Trials of thalidomide at the Royal Marsden Hospital have shown promising results in advanced RCC, possibly due to the down-regulation of some of these peptides including TNFα. Infliximab is a chimeric human / mouse monoclonal antibody against TNFα. We have performed a phase II study of this in pts with RCC. Methods:This was an open, single arm, phase II study using a 2 stage Gehan design. Eligibility criteria were: metastatic RCC progressing after immunotherapy (IFα +/or IL2), performance status (PS) 0–2, life expectancy of >12 weeks. Infliximab (5mg/kg) was administered on weeks 0, 2, 6, 14, 22, 30. Treatment could continue until progressive disease (PD). Response was assessed before each dose from week 6. Results:The first 15 patients are evaluable for toxicity and response (RECIST criteria). Median follow-up was 172 days (range 29–269). Median age was 57 (35–76). First-line immunotherapy included: IFα (n=11); IFα/IL2/5-Fluorouracil (n=4). Additional lines of treatment prior to study entry were given to 5 patients including IFα/IL2/5-Fluorouracil, GW57016, Vinflunine, B-Raf inhibitor, gemcitabine/capecitabine, medroxyprogesterone acetate. Patients received the following number of doses: 1 (n=15); 2 (n=15); 3 (n=10); 4 (n=4); 5 (n=3); 6 (n=1). 2 patients achieved partial response (PR) (12%) at 14 and 30 weeks. 1 late response (15 weeks) was observed following initial PD at 6 weeks. 5 patients have ongoing disease control (PR + stable disease) at 1,7,7,8,8 months. Probability of survival at 9 months is 92% (95% CI 54–99). Median progression free survival is 56 days (95% CI 37–75). Other than 1 episode of grade 3 hypersensitivity there were no significant toxicities. Conclusions:This study shows that infliximab is safe, non-toxic and active in RCC. 2 patients achieved PR and 1 patient had a late response despite initial PD. These early results are encouraging and suggest that infliximab may have an important role in the treatment of RCC. No significant financial relationships to disclose.
Evidence-based guidance for peer review “best practices” in radiation oncology.
Authors: Michael Donald Brundage, Jennifer O'Donnell, Margaret Hart, Lorella Divanbeigi Divanbeigi, Eric Gutierrez, Michelle Ang, Elizabeth Murray, Padraig Richard Warde
Journal: Journal of Clinical Oncology (2017)

180 Background: Peer review (PR) is an essential component of quality assurance in radiation oncology practice, endorsed by Canadian cancer agencies as a national standard of quality care. However, reported patterns of care studies indicate that PR practice varies considerably, including which contours (e.g., target volumes, organs at risk (OARs)), which dose parameters (e.g., OAR constraints, homogeneity criteria), which decision making points (e.g., decision to treat, selection of anatomical regions), and which treatment imaging parameters are included in the PR process. Both qualitative and quantitative evidence support the need for guidance on PR best practices. Here we report processes for the establishment of best-practice guidelines/minimal standards for PR. Methods: A comprehensive literature review was done to quantify PR findings for each of 3 cancer streams: head/neck, lung, and breast. This evidence summarized which aspects of radiotherapy plans were most frequently "flagged" at PR. A modified Delphi process was used to develop cancer site-specific PR guidance documents: appropriate stakeholders were first identified; a pre-meeting survey determined opinions on which plan elements are essential/important to review; a face-to-face meeting considered the evidence base and survey results to reach consensus. Parallel processes were conducted separately for each stream. Results: The literature findings were compiled to summarize the reported proportion of plans flagged by PR, and the nature of the flag (i.e. volumes, dose, OARs, other) for each cancer stream. Stakeholders included radiation oncologists, physicists, radiation therapists, and patients, specific to each stream. Draft guidance documents were created on the basis of stakeholder consensus regarding which components of PR were deemed essential; other important or “second tier” elements were also identified. Conclusions: Guidance documents including minimum standards for PR can be successfully created based on structured consensus development informed by available evidence. This guidance promises to reduce variation in PR thereby optimizing the efficiencies of PR processes, and increasing the quality of radiation treatment plans.
Impact of race and insurance status on time to breast cancer treatment across the US.
Authors: Aaron David Falchook, Jahan J. Mohiuddin, Ronald C. Chen
Journal: Journal of Clinical Oncology (2015)

e17568 Background: The IOM identifies timely treatment delivery as a health care quality indicator. We assessed whether race and insurance status were associated with delays in chemotherapy (C), surgery (S), and radiation (RT) in breast cancer. Methods: 771,219 newly diagnosed women from 2004-12 were identified from the National Cancer Database, which includes 70% of incident cancers across the US. Patients were stratified by treatment sequence to evaluate time interval between: 1) Diagnosis to definitive S, 2) Diagnosis to neoadjuvant C, 3) Lumpectomy to adjuvant RT, 4) Mastectomy to adjuvant RT, and 5) S to adjuvant C. Patients could be included in more than one analytic group. Linear regression was used to examine factors associated with time to treatment. Results: Time from diagnosis to initial treatment was longer for Black vs. White patients (Surgery median 35 vs 29 days, Chemotherapy 34 vs 28 days, all p <.001). Time to adjuvant treatment was also prolonged for Black vs. White patients (Lumpectomy to RT 47 vs 42 days, Mastectomy to RT 56 vs. 53 days, Surgery to adjuvant chemotherapy 42 vs 38 days, all p<.001). Similarly, uninsured patients experienced longer time to treatment (range = 5-8 days) vs privately insured. Women treated in community vs academic centers had shorter time from diagnosis to chemotherapy (28 vs. 33 days, p<.001) and surgery (25 vs. 35 days, p<.001). Differences in time to treatment by race and insurance (Table) and by facility type remained significant on multivariate analysis, which accounted for sociodemographics, comorbidity, year of diagnosis, and diagnostic variables. Conclusions: Black and uninsured patients experience delays at every step of initial and adjuvant treatments, with a cumulative delay of 2-3 weeks for women who receive trimodality therapy. Patients have quicker access to initiating treatment in community vs. academic centers. Diagnosis to C Diagnosis to S Lumpectomy to RT Mastectomy to RT S to adjuvant C β p β p β p β p β p Race White - - - - - Black 6.4 <.01 7.6 <.01 6.6 <.01 4.3 <.01 3.8 <.01 Hispanic 6.3 <.01 6 <.01 4.5 <.01 5.2 <.01 3.2 <.01 Insurance Private - - - - - None 7.0 <.01 5.8 <.01 6.7 <.01 2.0 0.12 5.5 <.01 Medicaid 6.6 <.01 6.4 <.01 7.0 <.01 5.6 <.01 5.8 <.01 Medicare 2.4 <.01 0.6 <.01 0.9 <.01 2.3 0.01 2.1 <.01
A retrospective analysis of patients with intermediate-risk germ cell tumor (IRGCT) treated at Indiana University from 2000 to 2010.
Authors: Costantine Albany, Shailesh R. Satpute, Mary J. Brames, Yaman Suleiman, Nawar Al Nasrallah, Susan M. Perkins, Nasser H. Hanna, Lawrence H. Einhorn
Journal: Journal of Clinical Oncology (2012)

4534 Background: Based on the International Germ Cell Cancer Collaborative Group (IGCCCG), IRGCT represents 26% of non-seminomas and 10% of seminomas with 2 year PFS of 74% (63-85%). Most patients are treated with 4 cycles of Bleomycin, Etoposide and Cisplatin (BEP). However, the optimal therapy for this heterogeneous group is not well defined. Our hypothesis was that many patients with IRGCT may not require BEPx4 as they are clinically closer to good risk rather than to poor risk disease. Methods: We conducted a retrospective analysis of all patients with testicular cancer seen at Indiana University (IU) between 2000- 2010. We identified 170 pts with IRGCT of whom 84 consecutive pts received their therapy at IU. 2 chemotherapy categories were identified: BEP (or equivalent) x4 or BEPx3 (+/-EPx1). Results: 45 pts received either BEPx4 (41), VIPx4 (2) or BEPx2 followed by HDCTx2 (2). 39 pts received BEPx3 (9) or BEPx3+EPx1 (30). Treatment decisions were based on clinical characteristics and markers amplitude. There were 78 (93%) non-seminoma, 6 (7%) seminoma. 27 (32%) stage II and 57 (68%) stage III. Mean AFP 3899 (range 1000-9550; n=50), mean hCG 16354 (range 5000-49000; n=34). The overall 1 and 2 year Kaplan-Meier estimates were 93% and 87% for PFS and 98% and 92% for OS. Results are depicted below. Conclusions: Our results for patients with IRGCT treated from 2000-2010 are superior to the IGCCCG pts treated from 1975-1990. Routine administration of BEPx4 probably represents overtreatment in a substantial percent of IRGCT. [Table: see text]