tbuckley/cabot-search huggingface dataset:
Are doctors responsible for delay in cancer management?
Authors: R. K. Karwasra, S. Bhanot
Journal: Journal of Clinical Oncology (2005)

6101 Background: Cancer patients in developing countries are still in advanced stage of their disease by the time they receive anticancer therapy despite rapid advances in medical sciences. It is commonly believed that this occurs due to late presentation of cancer patients to their physicians because of illiteracy, poverty and ignorance but is it true? Material and Methods: Cancer patients attending Surgical Oncology clinics between 2000 -2003 at Regional Cancer Centre, PGIMS, Rohtak in India were studied by detailed questionnaire in two phases to know the time of onset of symptoms, time of presentation of the patients to the physicians, details of the consultation and action taken thereafter by the physicians. Presentation interval (period from onset of symptoms to presentation of the patients), diagnostic interval (period from time of presentation to establishment of diagnosis of cancer) and treatment interval (period from establishment of diagnosis to initiation of anticancer therapy) were calculated. Delay was said to have occurred if presentation & diagnostic intervals exceeded one month each and treatment interval exceeded two weeks. The physicians to whom cancer patients presented first were called as primary care physicians (PCP) and were divided into 3 categories of qualified medical practitioner, qualified non-medical practitioner and unqualified medical practitioner.At the end a total of 1006 patients were available for analysis. Results: Majority of the patients has poor socioeconomic status with very low literacy level and three forth of them were not aware about cancer still 67.3% patients presented to primary care physicians without delay. 75.9% of the patients had delay at diagnosis level and physician was responsible for this delay in 60.4% of the patients. The unqualified physicians and qualified non medical practitioners almost never diagnosed cancer while 2/3rd of the qualified physicians also did not diagnose cancer but gave only symptomatic treatment. Conclusions: Despite poverty, illiteracy and poor cancer awareness majority of the patients presented without delay to their physicians but significant delay occurred in most of the patients at diagnosis level and physician was mainly responsible for this delay. No significant financial relationships to disclose.
Efficacy of early up-front red blood cell transfusion followed by maintenance epoetin support for anemia during chemotherapy: Results of the phase II pCATS study.
Authors: A. C. Ogilvie, J. W. R. Nortier
Journal: Journal of Clinical Oncology (2011)

e19622 Background: Rapid normalization of Hb might be of benefit in patients receiving chemotherapy to improve tumor oxygenation. This multicenter single-arm phase II study in anemic patients (Hb<11,3 g/dL) with metastatic solid cancers while receiving chemotherapy, aimed at rapid normalization of Hb levels (11,3-12,9 g/dL). The treatment consisted of a red blood cell-transfusion (RBCT) followed by Epoetin-alpha (Epo) weekly (40,000 IU s.c.). Epo was only administered after transfusion when the Hb level was below the lower margin of the target Hb range. Pre-emptive oral iron supplementation was given. Methods: 23 patients (19 were women), 44% had breast and 22% colorectal cancer, aged (median) 61 (range 33-89) years and a WHO Performance Status of < 3 (of 0 in 3, of 1 in 9 and of 2 in 11 patients), were enrolled from 2006-2009. Results: Patients were on study during a median of 92 (range 8 to 240) days. Two patients developed progressive disease (PD) directly after the RBCT. Two patients did not receive transfusions because their Hb increased spontaneously into the target range. A median of 2 (range 1-4) units of RBCT increased median Hb from 9,8 (range 8,6-12,4) g/dL to 11,1 (range 9,5-13,6) g/dL. Thereafter median Hb remained between 9,7-11,9 g/dL. Treatment was discontinued in 22 patients because of PD. The median general Quality of Life (by visual analog scale) increased marginally during the first 28 days on study. During RBCT and Epo administration, no treatment-related toxicity (like hypertension, thrombo-embolic events) occurred. Grade 3/4 adverse events and serious adverse events were considered to be related to chemotherapy or PD. Conclusions: During chemotherapy this rapid anemia treatment increased Hb immediately and was safe. RBC transfusions yielded lower Hb levels than expected, but administration of Epo thereafter was effective and safe for maintaining Hb in the low normal range during the chemotherapy period.
A phase I study of veliparib (ABT-888) in combination with capecitabine (C) and temozolomide (T) in patients (pts) with advanced well-differentiated unresectable neuroendocrine tumors (wdNET).
Authors: Ramya Thota, Kimberly Brown Dahlman, Tatsuki Koyoma, Jordan Berlin
Journal: Journal of Clinical Oncology (2016)

TPS466 Background: Veliparib (V) is a novel orally bioavailable PARP-1 and -2 inhibitor which potentially synergizes with temozolomide (T). A single arm phase II study combining C and T has shown promising activity in well-differentiated NETs with overall response rate of 43%. Hence, we propose to combine V with C and T optimizing the interaction of V with T by dosing the V during the T to produce improved clinical activity in pts with wdNETs. Methods: This is an investigator initiated, single institution, phase I, dose-escalation trial using a modified Toxicity Probability Interval (mTPI) design. The primary objective is to estimate the maximum tolerable dose (MTD), which is defined as the dose level at which the probability of dose limiting toxicities (DLTs) is 0.33. Secondary objectives include assessing safety profile, antitumor activity and progression free survival. Inclusion criteria: Pathologically confirmed metastatic unresectable well-differentiated (low grade and intermediate grade) NETs that demonstrate progressive disease in the prior 12 months, ECOG PS 0-2 and adequate organ function. Exclusion criteria: severe hypersensitivity reaction to C, 5-FU, T or dacarbazine or uncontrolled chronic illness. Prior treatment with both C and T. Administration and design: We initially will fix doses of C and T at C: 750 mg/m 2 po twice a day (BID) on days 1-14 and T at 100 mg/m2 po BID on days 10-14. V is given orally on days 10-14 along with T. We have 5 planned V dose levels (20, 40, 60, 80, 100 mg). If dose level 1 is too toxic we will go to C 600 mg/m 2 , T 75 mg and V 20 mg. Patients will be enrolled in cohorts of 3. The dose escalation/de-escalation will be as per pre-specified guidelines from the mTPI design. The planned sample size is 21 based on the anticipated number of patients available for this study within 18 months. This trial will be terminated when the maximum sample size (21) is reached or if the lowest dose is deemed too toxic. The study will start enrolling patients October 2015.
A self-assessment tool for safety and quality improvement in radiotherapy.
Authors: Todd Pawlicki, Peter Dunscombe, Eric Ford
Journal: Journal of Clinical Oncology (2012)

263 Background: The radiation treatment community has traditionally had a strong focus on the safety and quality of the care provided to cancer patients. Recent well publicized events in the United States and around the world have served to further sharpen this focus and have resulted in the generation of many reports offering advice and recommendations on how we could do better. While advice is plentiful, practical tools for the on-going improvement of safety and quality in radiotherapy are generally lacking. The online Safety Profile Self-Assessment Tool, described here, is being developed to fill this gap. Methods: The tool was built principally on three foundations: The Agency for Healthcare Research and Quality’s (AHRQ) validated survey tools, an analysis of recommendations in seven recent authoritative documents and the AAPM’s Work Group on the Prevention of Errors “Consensus recommendations for incident learning database structures in radiation oncology”. A core group developed a demonstration version of the tool. Both the content and functionality of this version were extensively discussed and further developed at a Workshop including representatives of ASRT, ASTRO, AAMD and SROA. Iterative refinement of the tool took place after the Workshop. Results: The tool is divided into four major sections: (1) Institutional Culture, (2) Quality Management, (3) Managing Change and Innovation, and (4) Clinical Performance. The fourth section, Clinical Performance, is further subdivided into the major steps in the radiotherapy process. The 90 safety/quality indicators take the form of statements with which the assessor identifies the degree of compliance on a five point Likert scale. An example of a Safety/Quality indicator isClinical staff submits reports of errors and near-misses.The assessor responds to this statement on a scale ranging from “Always” to “Never”. The online tool includes a Safety/Quality Improvement log to facilitate tracking the implementation of remedial actions taken in response to identified system weaknesses. Conclusions: An online tool to facilitate Safety/Quality improvement in Radiotherapy is at an advanced stage of development. The tool will be released for general use in the fall of 2012 and fully evaluated thereafter.
Personalized symptom goals in symptom assessment: A prospective multicenter study.
Authors: David Hui, Omar M. Shamieh, Carlos Eduardo Paiva, Pedro Emilio Perez-Cruz, Mary Ann Muckaden, Minjeong Park, Eduardo Bruera
Journal: Journal of Clinical Oncology (2015)

190 Background: PSG is a novel measure to assess treatment response in symptom management. In this multicenter prospective longitudinal observational study, we examined the PSG for 10 common symptoms in patients with advanced cancer, and identified the factors associated with PSG intensity and PSG response. Methods: We enrolled patients with advanced cancer seen at 5 outpatient palliative care clinics (USA, Jordan, Brazil, Chile and India). We assessed the intensity of 10 symptoms using the Edmonton Symptom Assessment Scale at first consultation visit and then a second visit 14-34 days later. We also assessed the PSG by asking patients “At what level would you feel comfortable with this symptom?” using the same 0-10 numeric rating scale for each symptom. Response was defined as symptom intensity ≤ PSG. We used multivariate logistic regression to determine factors associated with PSG intensity and PSG response. Results: 728 patients were enrolled from 5 palliative care clinics. The average age was 57 (range 19-85), 361 (50%) were female, and 29 (31%) were White. The medianPSG was 1/10 for nausea, 2/10 for depression, anxiety, drowsiness, well-being, dyspnea and sleep, and 3/10 for pain, fatigue, and appetite. In multivariate logistic regression, Asian ethnicity (odds ratio [OR] 2.4-8.2, P &lt; 0.001), CAGE positivity (OR 1.7-2.3, P &lt; 0.05) and higher baseline symptom intensity (ORs 1.08-1.15 per point, P &lt; 0.03) were associated with PSG ≥ 2 for essentially all symptoms. At visit 2, 34%-73% of patients had a PSG response, which represents a significant improvement compared to the first visit (P &lt; 0.05 except for depression, drowsiness and well-being). PSG response was associated with baseline PSG intensity (ORs 1.3-1.5 per point, P &lt; 0.001) and ethnicity (P &lt; 0.02) for physical symptoms, and male sex (ORs 1.45-1.65, P &lt; 0.02) for psychological symptoms. Conclusions: PSG was 3 or lower for a majority of patients, and varied according to ethnicity, alcoholism and symptom intensity. PSG response allows clinicians and researchers to tailor treatment goals, while adjusting for individual differences in scale interpretation and factors associated with symptom response.
Tumor profiling of 431 pancreatic tumors from elderly patients.
Authors: Joanne Xiu, Kevin Rakszawski, Sandeep K. Reddy, Yuxia Jia
Journal: Journal of Clinical Oncology (2016)

257 Background: Pancreatic cancer (PC) is frequently a disease of the elderly and controversy exists as to whether these patients benefit from aggressive treatments. We aimed to investigate biomarker features from tumors taken from elderly PC patients to identify therapeutic implications. We also compared the results to those from younger patients to assess differences. Methods: PC tumors were tested at Caris Life Sciences between 2009 and 2015 by immunohistochemistry, fluorescent/chromogenic in-situ hybridization and sequencing. De-identified biomarker data were analyzed. Results: A total of 431 tumors from PC patients aged &gt; = 75 were analyzed: 50% were samples from pancreas, 50% were from metastatic sites. 26 of 47 genes sequenced carried mutations with frequencies ranging from 0.6% to 84%. The highest mutation rates were seen in KRAS (84%), TP53 (55%), BRCA2 (21%), SMAD4 (12%), ATM (4.4%), BRCA1 (4.2%) and PIK3CA (3.8%). Overexpression of TOPO1 and low expression of ERCC1, RRM1 and TS were seen in 45%, 73%, 86% and 79%, respectively, indicating potential benefit from irinotecan, platinums, gemcitabine and fluoropyrimidine, respectively. Tumor expression of PD-L1 was seen in 14% and tumor-infiltrating lymphocyte expression of PD-1 was seen in 45%. Overexpression of EGFR and cMET were seen in 91% and in 62%, respectively. When compared to 470 tumors from PC patients aged &lt; = 50, KRAS mutations were significantly more common in the elderly than in younger patients (84% vs. 74%, p = 0.0018), while MLH1 mutations were seen exclusively in younger patients (0% vs. 4%, p = 0.0241). Moreover, expression of TOP2A (53%vs. 45%), ERCC1 (36% vs. 27%), RRM1 (20% vs. 14%), SPARC (20% vs. 14%) and PR (5% vs. 1%) were significantly more prevalent in the younger group (all p &lt; 0.05). Conclusions: Tumor profiling of 431 tumors from elderly PC patients suggests therapeutic opportunities including cytotoxic, biological as well as targeted agents for this patient group. A comparison with younger patients indicated that irinotecan, fluoropyrimidine and taxanes may provide equal benefit to elderly and younger patients, while platinums and gemcitabine may be more likely to benefit elderly patients.
Bevacizumab (Bev)-based therapy for patients (pts) with colorectal cancer (CRC): McGill University and Segal Cancer Centre experience.
Authors: D. W. Wasserman, N. Bouganim, G. Batist, P. Metrakos, P. Chaudhury, M. Hassanain, P. Kavan
Journal: Journal of Clinical Oncology (2011)

e14158 Background: Bev prolongs overall survival (OS) and time to progression (TTP) when added to standard chemotherapy for mCRC and was approved for use in this setting in Feb 04. Bev was not approved in Canada until Sep 05, resulting in potentially undertreated pts in the intervening period. Therefore, in conjunction with Roche Canada and the Segal Cancer Centre, we initiated a compassionate use program to provide access to Bev in a real-world setting. Methods: All pts had metastatic CRC and were Bev-naive. Pts were treated with Bev plus chemotherapy chosen at physicians’ discretion. Available pt data were collected from time of initial diagnosis to time of chart review, and included demographics, relevant medical history, staging/pathology at diagnosis, all treatment regimens including duration, grade 3/4 adverse events (AEs), primary tumor surgery, hepatectomies/other related procedures, and OS. Results: A total of 196 pts were treated (108 male; median age 56 years, range 18-79; Stage I 1%, II 8%, III 21%, IV 70%). At diagnosis, 78% of pts had moderately differentiated tumors, 18% poorly differentiated, and 4% were well-differentiated. Pts received Bev as first, second , thirs, fourth and later lines of treatment for metastatic disease (51, 44, 30, 18 and 11%, respectively). All pts received Bev plus chemotherapy as follows: irinotecan-based 74%, oxaliplatin-based 66%, irinotecan- and oxaliplatin-based 10%, 5-FU only 8%. Some pts received Bev across multiple lines of treatment with different combination partners. 24% of pts received Bev associated with primary tumor surgery and/or hepatectomy. Median duration of treatment was 7 months. Grade 3/4 or higher treatment-related AEs were experienced by 117 pts (60%). Grade 3/4 Bev-related AEs were seen in 20.4% of pts; the most common were thrombocytopenia 9%, deep-vein thrombosis 3% and pulmonary embolism 2.6%. At a median follow-up of 36 months, median TTP was 8 months (95% CI, 7-9). Median OS from time of diagnosis was 58 months (95% CI, 46-66). Conclusions: These data confirm the safety of Bev in pts with mCRC and across multiple lines of treatment. Promising efficacy data were also observed, including long-term survival in pts with advanced disease.
Perioperative outcomes following surgical resection of renal cell carcinoma with upper level IVC thrombus: A contemporary multicenter experience.
Authors: Edwin Jason Abel, R. Houston Thompson, Vitaly Margulis, Jennifer E. Heckman, Megan M. Merrill, Oussama M. Darwish, Laura-Maria Krabbe, Stephen A. Boorjian, Bradley C. Leibovich, Christopher G. Wood
Journal: Journal of Clinical Oncology (2014)

498 Background: Surgery for RCC patients with IVC thrombus above the hepatic veins is complex and associated with an increased risk of perioperative morbidity and mortality. However, minimal data exist that describe contemporary perioperative outcomes at major referral centers or the prognostic factors associated with adverse surgical outcomes. The objective of this study is to determine the preoperative predictors of major complications and 90 day mortality after surgery in RCC patients with IVC thrombus above the hepatic veins. Methods: Records were reviewed of all RCC patients with IVC tumor thrombus above hepatic veins who had surgery from 1/2000 to 12/2012 at Mayo Clinic, MD Anderson, UT Southwestern and the University of Wisconsin. Major complications were recorded were defined as 3A or greater according to the Clavien- Dindo system within 90 days of surgery. Univariate and multivariate (MV) analyses were used to evaluate associations of preoperative clinical, pathological or laboratory variables with risk of major complications or 90-day mortality. Results: A total of 162 patients were identified for study (thrombus level 3,4 in 69 and 93 patients, respectively, according to Neves classification). Cardiopulmonary bypass was used in 60/162 (37.5%), while 40 (24.7%) patients underwent pre-operative angioembolization. Major complications were reported in 55 (34.0%) patients, with the most common being respiratory (12.4%), hematologic (9.2%) and cardiac (8.6%). On MV analysis, preoperative systemic symptoms and level 4 thrombus were independently associated with an increased risk of major complications. Mortality was reported in 17 (10.5%) patients within 90 days after surgery. On MV analysis, ECOG performance status and low serum albumin were independently associated with increased risk of 90 day mortality. Conclusions: Contemporary perioperative mortality and major complication rates for RCC patients with upper level thrombus are 10 and 34%, respectively. ECOG PS &gt;1 and low serum albumin are associated with an increased risk of perioperative mortality, and should be considered when selecting patients for neoadjuvant systemic therapy trials.
A comparison of toxicity of gemcitabine versus platinum-based combined chemoradiation for muscle-invasive bladder cancer: The Memorial Sloan-Kettering experience.
Authors: Sujith Baliga, Xin Pei, Dean F. Bajorin, Jonathan E. Rosenberg, Bernard Bochner, Marisa Kollmeier
Journal: Journal of Clinical Oncology (2013)

313 Background: The optimal radiosensitizer for chemoradiation therapy for bladder cancer is unknown. We compared toxicities of concurrent platinum (plat) vs gemcitabine (gem) in this setting. Methods: 88 patients with muscle invasive bladder cancer (MIBC) who underwent concurrent platinum (n=26) or gemcitabine (n=62) chemotherapy with definitive external beam radiotherapy (median dose= 64.8Gy) were included in this analysis. Gem was delivered biweekly and platinum-based (cisplatin or carboplatin) chemotherapy given weekly or every 3 weeks. Treatment interruptions, cycle delays, and dose reductions were recorded. Acute (&lt;90 days) and late (≥90 days) toxicity was graded using CTCAE v4.0. Chi-square and fisher’s exact tests were used to compare groups with respect to stage, nodal status, tumor size, baseline urinary medication and Charlson co-morbidity index (CCMI). Results: Median follow-up was 18.5 mos. Mean age was 77 years (range 35-91). Gem patients were older (76 vs 63 years; p&lt;0.01) and had higher CCMI (p&lt;0.01). There were no significant differences in treatment interruption (8% vs 4%; p=0.67), cycle delays (52% vs 36%; p=0.24) or dose reductions (27% vs 12%; p=0.16) in the gem vs plat cohorts respectively. Hematologic toxicity was the most common reason in both groups. Acute and late grade ≥2 GU toxicity in the gem and plat cohorts were 30% vs 8% (p=0.03) and 8% vs 8%, respectively. More gem patients were on a baseline urinary medication (21% v 8%; p=0.22). Six patients developed urinary incontinence (all in gem cohort). One patient in the plat cohort developed late grade 3 hemorrhagic cystitis. Acute and late grade ≥2 GI toxicity in the gem and plat cohorts were 16% vs 12% (p=0.75) and 4% vs 3% (p=1), respectively. 2 patients (one in each cohort) developed acute grade 3 GI toxicity. Conclusions: Chemoradiation for MIBC with gemcitabine or platinum-based chemotherapy is generally well tolerated. In our series, despite older age and higher CCMI in the gem cohort, most (&gt;90%) completed treatment. Higher acute GU toxicity was noted in the gem cohort. Late grade 3 GU/GI toxicity was low and comparable amongst the two radiosensitizers.