tbuckley/cabot-search huggingface dataset:
Changes in expression levels of excision repair cross-complementing group 1 (ERCC1) and dihydropyrimidine dehydrogenase (DPD) during first-line oxaliplatin-based treatment of advanced metastatic colorectal cancer (mCRC).
Authors: Hideo Baba, Masayuki Watanabe, Hirohisa Okabe, Yuji Miyamoto, Yasuo Sakamoto, Yoshifumi Baba, Masaaki Iwatsuki, Akira Chikamoto, Toru Beppu
Journal: Journal of Clinical Oncology (2012)

520 Background: We previously reported the updated results of the FIRIS study, reconfirming the non-inferiority of IRIS (irinotecan/S-1) to FOLFIRI with progression-free survival (PFS) as the primary endpoint (ASCO2011 #3562). Moreover, in patients who had received prior oxaliplatin-based chemotherapy, median OS was significantly longer in the IRIS group than in the FOLFIRI group (adjusted HR=0.755, 95% CI: 0.580–0.987). The aim of this retrospective study was to elucidate molecular mechanisms underlying the better survival in the IRIS group among patients who had previously received oxaliplatin. Methods: Irinotecan-naive mCRC patients (ECOG PS 0–1, adequate organ function, resectable liver metastases) were enrolled. Resected liver metastases were available for 17 patients who had received FOLFOX and 21 patients who had received no prior oxaliplatin-based chemotherapy. Using laser captured microdissection and real-time RT-PCR, we analyzed mRNA expression of excision repair cross complementing group 1 (ERCC1) and dihydropyrimidine dehydrogenase (DPD), factors related to drug resistance and metabolism. Results: Baseline factors (sex, age, histology) of the subjects were similar in the two groups. Expression levels of nucleotide excision repair pathway gene ERCC1 and pyrimidine catabolic pathway gene DPD differed significantly between the FOLFOX group and non-oxaliplatin group. Mean expression levels of ERCC1 and DPD were respectively 1.9 and 7.4 times higher in the FOLFOX group than in the non-oxaliplatin group (ERCC1: 1.58 vs. 0.85, P=0.0005; DPD: 0.580 vs. 0.078, P=0.01). Conclusions: Increased expression of ERCC1 and DPD after first-line oxaliplatin-based chemotherapy is probably related to chemosensitivity to subsequent therapy. Tumor heterogeneity and clonal selection of tumor cells resistant to oxaliplatin may also be involved.
The possibilities of treatment of gastrointestinal stromal tumors.
Authors: Stanislaw Gluszek, Dorota Koziel, Jarosław Matykiewicz, Rafal Rylski
Journal: Journal of Clinical Oncology (2015)

222 Background: Gastrointestinal stromal tumour (GIST) is the most common mesenchymal tumour of digestive tract, presesting less than 1% of all digestive tumours. This study is analyse a group of patients treated surgically due to GIST. Methods: The group of 71 patients consisted of 34 males and 37 females between the age of 32 and 89 (M 44-83, average 64.6; F 43-89, average 66.5) treated surgically due to GIST. Analysis included clinical symptoms, diagnosis, surgical treatment, location of tumour, outcome of histopathological and immunohistochemical examinations, recurrence of disease, metastases and mortality rate. Results: Among 71 GIST patients 35 were with low aggressivity level, 14 with average and 22 with high. Most of patients were subjected to surgical treatment (laparoscopic or open) on a planned basis and in 3 cases on an emergency basis due to the intensified symptoms of intestinal occlusion, 50 patients were found to have gastric tumours, 3 duodenal tumours, 13 small intestine tumours, 3 colonic tumours, 2 rectal tumours. Histopathological examination outcome showed radical tumour resection in all cases Tumours of size exceeding 5 cm in diameter were found in 30 cases. Most patients had definited type of mutation. Predominated mutations localized in exon 11. There was no perioperative mortality rate. During follow up (from 1 month to 130 months), 16 patients died, including 4 due to GIST dissemination, 4 were diagnosed with recurrence of GIST and two of them were qualified for imatinib treatment others died of cardio-vasculary diseases. Most of patient underwent resection of tumor with safety margin of gastric wall (21), 5 patients were treated by laparoscopic surgery. All patients, who subsequently had postoperative recurrence or died due to GIST metastases, were diagnosed with highly aggressive tumor. Conclusions: GIST - still unknown treatment possibilities [surgery, imatinib, other specific tyrosine kinase inhibitors, what next?]. Analysis of cases from our study confirms that large size of tumor (diameter &gt; 5cm) and high mitotic index (MI &gt;5/50 HPF) are factors associated with bad prognosis (metastases, recurrence).
Interpreting first-line options in mRCC: A look into the German RCC-registry.
Authors: Peter J. Goebell, Lothar Mueller, Friedrich Overkamp, A. Lueck, Michele Vogt, Norbert Marschner
Journal: Journal of Clinical Oncology (2014)

429 Background: During the last few years, several efficacious therapeutic options have been developed for patients with metastatic renal cell carcinoma (mRCC). Due to the variety of multiple new targeted therapeutic options evidence based solely on randomized clinical trails is lacking. Registry data represents an important supplement providing insight into the treatment course and evidence on various outcomes. However, results provided by registry data may be influenced by many factors such as patient characteristic and comorbidities. Matched-pair analyses provide an interesting tool to compare different treatment options. Material &amp; Methods: Over 100 oncology and urology outpatient centers in Germany are actively participating in this registry. The enrolment of the first 1000 mRCC patient data-sets with a maximum follow-up of three years has recently been completed. Among other information, data on patient and tumor characteristics, all systemic antineoplastic treatments, dosages, as well as response rates, progression free survival and overall survival are documented. Results: At the start of systemic therapy mean age were 66.2 years for male and 69.0 years for female patients, respectively. For all patients at least one comorbidity was indicated (Charlson Comorbidity Index 1.0). More than 94% of patients had metastases at inclusion. Investigating the most prominent TKIs used in sequential treatment in the registry, we identified time from initial diagnosis to treatment start as one of the most important factors predicting overall survival. Surprisingly, when controlling for this factor in a matched-pair analysis together with age, gender and risk, outcome in terms of progression-free survival appears to be similar in first line treatment with either Sunitinib or Sorafenib. Conclusions: Registry data can provide missing pieces of evidence on treatment outcomes. The registry demonstrates once more its hypothesis generating character and thus adds to the body of evidence as established from clinical trials. A direct comparison of efficacy can only be provided by clinical trails whereas registry data represent effectiveness of real-life treatment.
Toward quality peer review: Outcomes of peer review across provincial radiation oncology programs.
Authors: Julie Rouette, Jennifer O'Donnell, Sophie Foxcroft, Margaret Hart, Eric Gutierrez, Lindsay Elizabeth Reddeman, Gunita Mitera, Padraig Richard Warde, Michael Donald Brundage
Journal: Journal of Clinical Oncology (2016)

205 Background: Review of treatment plans by a second radiation oncologist is an important quality indicator in radiation oncology. Peer review (PR) can improve quality of care in individual patients by detecting clinical and planning issues and recommending plan changes. This study reports the frequency and nature of these changes across all 14 radiation oncology programs (ROPs) in Ontario, Canada. Methods: We identified all peer-reviewed curative treatment plans delivered in Ontario within a 3-month study period between Dec 2013-Nov 2014 using Cancer Care Ontario’s Activity Level Reporting System, where data on treatment intent and date, disease site treated, PR status, timing of PR, and nature of recommended changes were available. Results: There was considerable variation in the proportion of plans peer-reviewed across ROPs (70.2%, range: 40.8-99.2%). Over the study period, 5,561 curative treatment plans were peer-reviewed and 3.3% had changes recommended. Of those, 21.0% had major clinical and re-planning implications. Recommended changes most often involved minor (63.1%) vs major (36.9%) re-planning implications. Highest proportions of changes were recommended for the treatment of the esophagus, uterus, upper limb, cervix, lower limb, H&amp;N, bilateral lung, right supraclavicular nodes, rectum, and spine (5.0%-7.0%). Plans involving the left breast had slightly more changes recommended (3.0% [95%CI:2.0%-4.5%]) vs right breast (2.4% [95%CI:1.5%-3.8%]). Recommendations were more frequently made when PR was conducted pre-radiotherapy (3.8%) vs during (1.4%-2.8%; p = 0.005), however the nature and implementation of changes were not statistically associated with the timing of PR (p = 0.91; p = 0.23, respectively). Proportion of recommended changes to treatment plans was not statistically associated with ROP patient volume (p = 0.08), proportion of plans peer-reviewed (p = 0.36) or academic status (p = 0.75). Conclusions: Significant variation exists in the proportion of recommended changes across all disease sites and ROPs. PR seems effective in detecting treatment plans with important clinical and planning issues; strategies should be developed to optimize its conduct in radiation oncology.
A Phase II Randomized, Double-Blind, Eight-Arm, Parallel-Group, Dose-Response Study of Apixaban, a New Oral Factor Xa Inhibitor for the Prevention of Deep Vein Thrombosis in Knee Replacement Surgery - On Behalf of the Apixaban Investigators.
Authors: Michael R. Lassen, Bruce L. Davidson, Alexander Gallus, Graham Pineo, Jack Ansell, David Deitchman
Journal: Blood (2006)
Informing women about letrozole after tamoxifen. Is there an easier way?
Authors: D. Grenier, S. Latosinsky, W. Martin
Journal: Journal of Clinical Oncology (2005)

898 Background: Letrozole reduces breast cancer recurrences in postmenopausal women following completion of 5 years of tamoxifen. Providing informed decision-making for the large number of women eligible, now and in the future, creates a considerable burden on oncology physician resources. This may result in delays in information dissemination and treatment. Objectives of this study are to develop a self-administered decision-making guide for women eligible to take letrozole post tamoxifen and to determine the effect of this guide when included with a letter of invitation to discuss letrozole therapy. Methods: Women currently over 50 years of age, who had stage I-III, ER/PR positive or unknown breast cancer diagnosed between 1997 and 1999 and without recurrences, were identified from the Manitoba Cancer Registry. All women received a letter of invitation to make an appointment with an oncologist to discuss letrozole. They were randomized to receive a decision-making guide either with the letter (G1) or just prior to meeting with the oncologist (G2). The guide was developed with input from both health care professionals and two focus groups of women with breast cancer experieence. The number of oncology appointments and prescriptions for letrozole were compared between the two groups using chi-squared tests. Results: 159 women were sent letters and 44 (27%) requested appointments. Of these, 17 of 76 (22.4%) were in G1 and 27 of 83 (32.5%) were in G2. The 10.1% difference in appointment requests was not significant (p= 0.15, 95% CI 0 to 34%). Of the 30 women seen so far, 16.7% took letrozole, 46.7% declined and 36.6% were undecided. The numbers are too small to further compare the two groups. Conclusions: A decision-guide was developed that was acceptable to both clinicians and focus groups of breast cancer survivors. Interest in letrozole was surprisingly low overall, even in women who saw an oncologist. Timing of the decision-guide did not appear to affect the numbers of appointments requested nor prescriptions for letrozole. No significant financial relationships to disclose.
A statewide evaluation of adjuvant chemotherapy for stage III colon cancer.
Authors: N. J. Petrelli, S. S. Grubbs, J. E. Spellman, C. L. English, A. Shevock, K. Nunley
Journal: Journal of Clinical Oncology (2011)

e14034 Background: Because of patient (pt) refusal or co-morbidity conditions, the optimal percentage of individuals receiving adjuvant chemotherapy has not been described in literature. This was evaluated in Delaware. Methods: A retrospective review of patient records of those not receiving adjuvant chemotherapy for stage III colon cancer (CC). The Delaware Cancer Registry (DCR) contained 296 stage III CC cases diagnosed from 2003-06 with receipt of adjuvant chemotherapy, treatment data or receipt of chemotherapy unknown. For the treatment unknown group, the DCR queried the submitting hospital to verify whether any additional treatment data was available in the hospital cancer registry. A refined list of 91 pts with no record of chemotherapy became the study group. A three-physician team assembled to review the records at the hospital that provided the treatment. An epidemiologist from the Delaware Division of Public Health oversaw study protocol, accompanied the physician team during reviews, and provided the necessary forms to standardize the data collection. Results: 91/296 (30.7%) patients with stage III CC were documented not to receive chemotherapy. 45 (49%) males , 46 (51%) females. 73 patients (80%) Caucasian, 17 (19%) African-American, one individual (1%) listed “Other Race”. 32/ 91 pts who did not receive chemotherapy (35%) were age 85 or older; another 38 (42%) between the ages of 75 and 84, and the remaining 23% were 74 years of age and under. All 45 patients between the ages of 30 and 54 received chemotherapy. The documented reasons for lack of chemotherapy, with patient frequencies: (a) pt co-morbidities (N=45; 49.5%); (b) pt expired postoperative (60 days) period (N=16; 17.6%); (c) pt refusal (N=13; 14.3%); (c) age (N=8; 8.8%); (d) pt lost to follow-up (N=2; 2.2%); and (f) unknown reasons (N=7; 7.7%). Conclusions: In Delaware, 70% of pts received systemic chemotherapy .90% of untreated pts had valid reasons not to receive chemotherapy. Medical co-morbidity, pt refusal and early death accounted for 82% of the absence of chemotherapy and were associated with advancing pt age. This statewide analysis suggests that a maximum population based adjuvant chemotherapy utilization rate of 70% exists for stage III colon cancer.
Anxiety in family caregiver of hospitalized patients with cancer: An opportunity for early intervention.
Authors: O. Castillo, N. De Gracia, G. Solis
Journal: Journal of Clinical Oncology (2011)

e19654 Background: Involving family caregivers in the hospital care of their loved ones may result in positive outcomes for patients and their families. Previous studies have found increased anxiety levels in primary caregivers of non-hospitalized cancer patients. However, there is a paucity of studies evaluating anxiety in the hospital setting. The purpose of this study was to investigate the prevalence of anxiety in family caregivers of hospitalized cancer patients. Methods: Caregivers whose patient stayed for more than five consecutives days during August to September 2010 were interviewed. Data were collected using a socio-demographic questionnaire and the Beck Anxiety Inventory (previously validated to Spanish language). Results: 57 caregivers were interviewed. Anxiety prevalence was 35% (95% CI 22.6-47.3). Factors associated with a high anxiety scores were female gender of the caregiver (p=0.009) and long hospitalization time (p=0.041). In addition, age less than 40 years (p=0.038), being a mother/ father caregiver (p=0.046) and indication for chemotherapy/ radiation therapy (p=0.025) were associated with higher anxiety punctuation in Beck Anxiety Inventory, as compared with age more than 40 years, being son/daughter caregiver and hospitalization for surgery. Conclusions: Identifying caregiver at high risk may help the health care team to intervene earlier and effectively to meet family caregiver's needs. Support groups and recreational activities during hospitalization are measures highly recommend in this situation.
Combined modality treatment has similar benefits in elderly (≥65 years) and younger patiets with esophageal cancer
Authors: B. R. Bird, G. O’Sullivan, O. S. Breathnach
Journal: Journal of Clinical Oncology (2005)

8277 Background: Combination therapy is a standard of care in esophageal cancer, however it is uncertain if elderly patients benefit as much as younger patients. To establish a baseline for future comparison a retrospective analysis was performed to assess this question. Methods: Between 1997 and 2001, 80 patients (57 male, 23 female) underwent surgery for oesophageal cancer at our institution, the regional centre for this disease. This analysis compares the outcome between patients aged ≥ 65 years with those <65 years. Patients had bronchoscopy, esophago-gastro-duodenoscopy, staging computed tomography and laparoscopy prior to either immediate resection or neoadjuvant treatment with concurrent 5FU/Cisplatin and radiation Results: The median survival (95% CI) was 23 months (12,34) for the whole population. In patients aged <65 (n=42) the median survival with surgery alone (n=29) was 27 months but 33 months in patients who had neoadjuvant chemoradiation (n=13). This difference was not statistically significant. Patients ≥ 65 had a median survival of 25 months with neoadjuvant chemoradiation (n=8) and 11 months with surgery alone (n=30). Due to small numbers this was not statistically significant. X2 (1 df): 0.6776, P = 0.4104. Baseline characteristics were similar in the two groups. Conclusions: Our findings suggest that there may be a benefit to combined modality treatment. Elderly patients appear to derive an equivalent benefit from neoadjuvant chemoradiotherapy. The outcome of future patients will be compared to the baseline established in this retrospective audit. No significant financial relationships to disclose.
Incidence of anthracycline-induced cardiotoxicity in patients with breast cancer: A single center's experience.
Authors: O. Nadeem, C. Rauwerdink, V. L. Beggs, D. D. Parr, A. T. Kono, G. N. Schwartz
Journal: Journal of Clinical Oncology (2011)

1093 Background: Cardiotoxicity is a known complication of anthracycline (A) and trastuzumab (T) therapy, but recent data suggests that it may be underreported. An asymptomatic decline in left ventricular ejection fraction (LVEF) may develop over time and no guidelines exist regarding the optimal duration of follow up. This study was performed to determine the incidence of A or T-associated cardiotoxicity in a large breast cancer population and to identify additional risk factors. Methods: We performed a retrospective chart review using the electronic medical record database at Dartmouth-Hitchcock Medical Center to identify patients with an ICD-9 coded diagnosis of breast cancer (174.9) and congestive heart failure (428, 428.0, 428.1, 428.9, 425, 425.9) from 1999 to 2009. A chart review was subsequently performed to identify a cohort who received A and/or T and who subsequently developed cardiotoxicity, defined as a decline in LVEF to ≤50% on echocardiography or MUGA scan. Additional data on co-morbidities was collected. Results: Four hundred and twelve patients were identified with breast cancer and congestive heart failure, 85 of which were treated with A with or without T. Of the 85 patients, 32 were judged to have A or T-associated cardiotoxicity. Seven hundred ninety three patients were treated with A during this 10 year period, resulting in a 4% incidence of heart failure in our A-treated population. The median age of the affected patients was 58 years (range 30-85) with a mean nadir LVEF of 34%. The mean cumulative doxorubicin dose was 261 mg/m2 (range 0-560). Common co-morbidities included hypertension (11/32, 34%), dyslipidemia (9/32, 28%) and smoking history (9/32, 28%). Chest wall radiation was administered to 22/32 (69%), with 9/22 (41%) left-sided and 13/22 (59%) right-sided. Heart failure symptoms were documented in 14/32 (44%) patients. Conclusions: The incidence of A and T-related cardiotoxicity at our institution was relatively low. Hypertension, dyslipidemia and smoking history were common but not enough to be classified as risk factors. Over half of the patients were asymptomatic, thus follow up assessment of LVEF in asymptomatic patients after completion of therapy may be warranted.
Assessment of single screening questions for dysphagia for routine clinical use in a tertiary care practice.
Authors: Catherine Brown, Ashlee Vennettilli, Deval Patel, Katherine Zora Zeman, Anthea Lau, Qin Kuang, Kevin Boyd, David Cella, Helen Mackay, Gail Elizabeth Darling, Rebecca Wong, Wei Xu, Geoffrey Liu, Doris Howell
Journal: Journal of Clinical Oncology (2014)

102 Background: Dysphagia is a common symptom among esophageal cancer patients. However, there is neither a validated PROMIS tool nor a validated PRO-CTCAE tool for this symptom. Clinically, obtaining patient-reported data on this symptom systematically in specific disease sites is important, but keeping the patient survey burden low means that this may be best done using a screening question first. The goal of this study was to assess the performance of such a screening question when compared to a more standard tool for measuring dysphagia, FACT-E, in a esophageal cancer outpatient clinic setting. Methods: Adult esophageal cancer patients seen at the Princess Margaret Cancer Centre between 2012-2014 were all seen by a multidisciplinary practice. Patients completed the FACT-E and screening symptom surveys at regular timepoints. The time point where the most severe set of symptoms was present for each patient was analyzed and severity of symptoms was compared against two 5-level screeners ("How are you currently eating?" (screener 1) and "I can swallow naturally and easily" (screener 2). Prevalence of symptoms, sensitivity (Se) and specificity (Sp) of the screeners was assessed. Complete data was available and analyzed in 173 (87%) of 199 patients. Results: Mean age (range) was 64 (23-89) and 75% were male. Prevalence of moderate to severe difficulty swallowing solid, soft, liquid foods and choking was 31%, 10%, 7%, 4% respectively. 34% of patients experienced at least one moderate to severe symptom of dysphagia. Screener 1 had a Se of 84% and Sp of 79% when using any moderate or severe swallowing problem as the reference. The Se and Sp of screener 2 was 51% and 87%, respectively. Conclusions: Up to a third of esophageal cancer patients experience moderate to severe symptoms of dysphagia. Screener 1 had the better performance as a screening tool. High completion rates in this practice suggest that routine systematic collection of such data is feasible, and perceived to be important to patients. Practice level projects can improve the quality of measuring symptoms. In the future we will be testing the role of mobile and computer technology for the routine collection of dysphagia and other symptoms in this practice setting.