tbuckley/cabot-search huggingface dataset:
Mortality reduction in the Swedish mammography screening program.
Authors: P. H. Zahl, J. Mæhlen
Journal: Journal of Clinical Oncology (2011)

29 Background: The introduction of a nationwide mammography screening program in Sweden in 1986 was associated with a 50% persistent increase of breast cancer incidence (including carcinoma in situ). Whether screening has been instrumental in a recent decline in the breast cancer mortality remains an open question. Methods: We compared the 18 years breast cancer mortality for two groups of women; those diagnosed in the first 6 years of the screening program and those diagnosed during a 6 year period that included the last 4 years before screening started and the first 2 years of the screening program. The test group (n + 328,927) included women aged 40 to 69 at the first invitation to screening. On average the women in the age-matched control group (n + 317,404) were born 4 years earlier then the women in the test group. The numbers of incident invasive breast cancers in each county were obtained from the Swedish Cancer Registry (in-situ cancers were excluded) and the corresponding breast cancer deaths were obtained from the Swedish Causes of Death Registry. Results: After 18 years follow up, the mortality reduction was 14% in the test group. However, most of this difference (10%) occurred in the first five years after diagnosis reflecting improved medical treatment of breast cancer. Most of the 14% difference also disappeared if we adjusting for period effects. Conclusions: About 83% of women in the test group were also included in the control group making the two groups almost identical with respect to risk variables. By screening the control group at the end of a 6-year period, the results are adjusted for differences due to lead-time bias and by studying mortality instead of survival overdiagnosis (length time bias) is also adjusted for. We conclude that organized mammography screening is not an important cause for the reduction in the breast cancer mortality in Sweden.
The role of fPSA, [-2]proPSA and the Prostate Health Index for the early prediction of outcome in patients with metastatic castration resistant prostate cancer on therapy with abirateroneacetate.
Authors: Katrin Schlack, Laura-Maria Krabbe, Okyaz Eminaga, Axel Semjonow, Martin Boegemann
Journal: Journal of Clinical Oncology (2016)

241 Background: Abiraterone acetate (AA) prolongs overall survival (OS) in pre- and post-chemotherapy setting in patients with metastatic castration resistant prostate cancer (mCRPC). Biomarkers to predict response to therapy are limited. Prostate-specific antigen (PSA) and lactate dehydrogenase (LDH) are commonly used as response-indicators but are often misleading during early therapy. Assays for circulating tumor cells, which can be surrogate for poor survival, are not routinely available at most places. In this retrospective study we evaluated the role of the PSA-derivatives free PSA (fPSA), [-2]proPSA (p2PSA) and the prostate health index (PHI) in addition to PSA as indicators of response during early AA-therapy. Methods: Twenty-five men with mCRPC receiving AA between March 2012 and July 2015 at the University Hospital of Muenster were included and analyzed. The PSA response rate (RR) was monitored according to PCWG2-criteria. Dynamic PSA-, fPSA-, p2PSA- and PHI-changes at 8-12 weeks under therapy were analyzed as predictors of progression free survival (PFS) and OS using Kaplan-Meier-analysis (KMA) and uni- and multivariate cox-regression analysis (UVA and MVA). Results: Twenty men were chemotherapy naïve, 5 pretreated with docetaxel. The PSA RR was 44%. In patients with &lt; or ≥ 12 months of PFS the relative change of median PSA and fPSA at 8-12 weeks compared to baseline differed significantly (p = 0.022 and 0.030). For men with ≤ or &gt; 15 months of OS there was a trend for a difference in relative change of median fPSA (p = 0.058). In KMA declining fPSA at 8-12 weeks was associated with a median OS of 32 months compared to 21 months in men with rising fPSA. In UVA rising PSA and fPSA were non-significant predictors of poor OS (Hazard ratio (HR) = 1.3 and 2.5 (p = 0.717 and 0.159)). In MVA PSA and fPSA were independent predictors of poor survival (HR 6.7 and 12.8 (p = 0.050 and 0.012)). Conclusions: fPSA is easily available and cheap. When added to PSA information, change of fPSA at 8-12 weeks of AA therapy may be a promising therapy control marker to help physicians to make decisions weather to stop or to continue AA therapy in men with mCRPC.
Three-year outcomes of GCR-3: A phase II randomized trial comparing conventional preoperative chemoradiation (CRT) followed by surgery and postoperative adjuvant chemotherapy (CT) with induction CT followed by CRT and surgery in locally advanced rectal cancer.
Authors: C. Fernandez-Martos, C. Pericay, A. Salud, B. Massuti, V. Alonso, M. J. Safont, R. Vera, M. P. Escudero, J. Maurel, J. Aparicio
Journal: Journal of Clinical Oncology (2011)

3552 Background: Compared with postoperative adjuvant Capecitabine/Oxaliplatin (CAPOX), induction chemotherapy before to CRT had similar pCR rates, but did achieve more favourable compliance and toxicity profiles as we previously have published. (J Clin Oncol 28:859-865, 2010). We now report on the 3-year outcomes of this randomized trial. Methods: Patients with locally advanced rectal cancer and stratified by institution, were randomly assigned to arm A—preoperative CRT with capecitabine, oxaliplatin, and concurrent radiation followed by surgery and four cycles of postoperative adjuvant CAPOX—or arm B—induction CAPOX followed by CRT and surgery. The following three-year outcomes were assessed: the cumulative incidence of local-regional (LRF) and distance failure (DF), disease-free (DFS) and overall (OS) using the Kaplan-Meier method. Results: Of 108 patients accrued, 103 were analyzable for outcomes. With a median follow-up time of 39.3 months (0.1-53), the 36 DFS rates were 68% (95% CI, 53% to 80%) for arm A and 70% (95% CI, 55% to 80%) in arm B. (p=0.97). The 36-month overall survival rates were 90% (95% CI, 77% to 96%) and 81%(95% CI, 68%to 89%) for arms A and B, respectively (p= 0.18). 11 patients experienced relapse in arm A (1 local, 10 distant),and 12 experienced relapse in arm B (2 local, and 10 distant). p = 0.6036. Conclusions: Although not powered to draw any comparative conclusions, induction CT prior to CRT and surgery for the treatment of locally advanced rectal cancer yields similar three-year outcomes as standard strategy. Because of the associated acute toxicity sparing and better compliance, a larger trial is warranted with this strategy.
Phase I safety study of farletuzumab, carboplatin, and pegylated liposomal doxorubicin (PLD) in patients with platinum-sensitive epithelial ovarian cancer (EOC).
Authors: Kenneth H. Kim, Danijela Jelovac, Deborah Kay Armstrong, Susan Weil, Martin Phillips, Benjamin M Schwartz, Jacob Michael Estes, Ronald David Alvarez
Journal: Journal of Clinical Oncology (2012)

5062^ Background: Farletuzumab (FAR) is a humanized monoclonal antibody that binds to folate receptor-α, a target which is largely absent in normal epithelium and over-expressed in EOC. A phase I and a phase II study indicate potential utility of FAR in combination with carboplatin/paclitaxel in recurrent platinum sensitive EOC. This study assessed safety and efficacy of FAR in combination with PLD/carboplatin, which has been demonstrated to have greater efficacy than carboplatin/paclitaxel in women with platinum-sensitive EOC. Methods: A multicenter, single-arm study enrolled 15 patients with platinum-sensitive EOC in first or second relapse defined by either CA-125 or RECIST. The primary endpoint is to assess safety of FAR plus PLD/carboplatin in this population. Patients were treated with weekly FAR 2.5 mg/kg plus carboplatin AUC 4-5 and PLD 30 mg/m 2 every 4 weeks for 6 cycles, followed by maintenance treatment with single agent FAR until disease progression. Initial dosing of weekly 2.5 mg/kg was later amended to 7.5 mg/kg every 3 weeks. Results: 13 of 15 patients completed 6 cycles of combination therapy; one received a total of 12 cycles of chemotherapy. Two patients progressed during combination therapy: one received 3 cycles, the other 5 cycles. The median number of subsequent single agent maintenance cycles was 8 (range 0-13). No grade 4 toxicities were observed. Of 20 grade 3 toxicities in 14 patients, 3 (1 fatigue; 2 small bowel obstructions in the same patient) were deemed by the investigator to be possibly related to FAR. These events were seen during the combination phase and were deemed by the investigator to be also possibly related to chemotherapy. All patients demonstrated clinical benefit: 1 complete response, 10 partial response and 4 stable disease. 7 patients have come off study, all for disease progression; a median PFS of 11 months was noted. 8 patients remain on study. Conclusions: These preliminary data indicate that the safety profile of FAR in combination with carboplatin and PLD is consistent with that historically recorded for carboplatin and PLD alone. Complete safety profile will be assessed; PK data and final results will be presented.
The Dutch Upper GI Cancer Audit: 2011-2014.
Authors: Linde A.D. Busweiler, Bas P.L. Wijnhoven, Mark I. van Berge Henegouwen, Daniel Henneman, Michel W.J.M. Wouters, Richard van Hillegersberg, Johanna W. van Sandick
Journal: Journal of Clinical Oncology (2016)

309 Background: In 2011, the Dutch Upper GI Cancer Audit (DUCA) group started with a nationwide registration of all patients who underwent surgery for esophageal or gastric cancer. The aim of this study was to describe the initiation and implementation of the DUCA and to provide an overview of the results. Methods: The DUCA is part of the Dutch Institute for Clinical Auditing. It provides (surgical) teams with reliable, weekly updated, benchmarked information on process and (casemix-adjusted) outcome measures. A web-based registration was designed, based on a set of predefined quality measures. Results: Between 2011 and 2014, a total of 4672 patients with esophageal or gastric cancer was registered in the DUCA. Case ascertainment has approached 100% for patients registered in 2014. The percentage of patients with esophageal cancer starting treatment within 5 weeks after diagnosis significantly increased over time (33 to 41%) and the percentage of patients with a minimum of 15 lymph nodes in the resected specimen significantly increased for both esophageal cancer (50 to 73%) and gastric cancer (48 to 74%). Postoperative mortality decreased for patients with gastric cancer (8.0% in 2011 to 4.0% in 2014; p = 0.020) and remained stable (around 4%) for patients with esophageal cancer. Conclusions: Nationwide implementation of the DUCA has been successful. Results give a valuable insight in the quality of the surgical care for patients with esophageal or gastric cancer and show a positive trend for various process and outcome measures.
A review of patient self-reported symptom data with a focus on pain.
Authors: Diane Denny, Swetha B. Nutakki, Kayla Alston, Maurie Markman
Journal: Journal of Clinical Oncology (2014)

79 Background: Cancer Treatment Centers of America, Inc (CTCA) is a national network of five hospitals that specialize in the treatment of patients fighting complex or advanced-stage cancer. The Symptom Inventory Tool (SIT) is an assessment tool that captures the patients’ perceived symptom burden. It includes the scientifically validated M. D. Anderson Symptom Inventory core items and is supplemented by CTCA clinician interested ‘custom 8’ (constipation, swelling, mouth soreness, bleeding, sexual interest, family, hope and Quality of Life). Methods: A baseline assessment is administered to new patients. Follow ups are assessed every 21 days or greater. The patients’ answers range from 0 to 10 and a score of 8 or higher was considered a severe symptom. A change of 2 points from baseline to 2nd follow up assessment is considered a clinically significant. Patients who had a severe pain score on a baseline assessment between April 2013 and March 2014 were closely followed. Results: There were 6,836 baseline assessments and 2,961 2nd follow up assessments between April 2013 and March 2014. Fatigue and sleep were the most reported symptoms while bleeding, mouth sores and vomiting were the least reported. Most of the patients had a decrease or stayed unchanged in their symptom scores. The patients who had a significant increase in symptoms at follow up ranged from 6% for bleeding to 28% for fatigue. There were 462 patients who reported severe pain on baseline assessment. Of the 462 patients, 295 patients (63.8%) had improvement in severity by the follow up assessment. After chart review, 447 patients (96.7%) had either improvement by follow up assessment (63.8%) or documented pain intervention (32.9%). Interventions included change to pain medication, addition of a Medtronic pain pump, physical therapy, palliative radiation therapy, cold laser therapy, and integrative therapies such as acupuncture, chiropractic care and massage therapy Conclusions: The SIT was successful in identifying symptom burden and interference with life issues in oncology patients. It has become an integral part of patient care at CTCA in providing exceptional pain and symptom management through the disease process creating visibility and focus.
Fever during cancer chemotherapy: Analysis of 1,016 chemotherapy cycles.
Authors: D. Ogawara, M. Fukuda, Y. Nakamura, S. Ueno, N. Suyama, K. Nakatomi, T. Iida, T. Kanda, M. Oka, S. Kohno
Journal: Journal of Clinical Oncology (2011)

e13013 Background: Cancer chemotherapy has risk of severe infection due to neutropenia. Indication of antibiotics tends to expand. Meanwhile, abuse of antibiotics encourages the growth of organisms resistant. This study was undertaken to analyze the fever during cancer chemotherapy to reduce unnecessary uses of antibiotics. Methods: Retrospectively, 1,016 cycles of patients who have treated with cancer chemotherapy in Division of Respiratory Diseases, Kawasaki Medical School and Nagasaki Municipal Hospital were analyzed. The temperature equal or more than 37.5 degree were detected as fever. One chemotherapy cycle of one patient was counted as one. Results: Patients characteristics: male/female = 748/268, median age (range) = 68 (29-88), lung cancer / malignant pleural mesothelioma / others = 949/52/15. Fever observed in 367 cycles (36%), 280 cycles (37%) in male, 87 cycles (32%) in female. Day 4 (8%), day 3 (7%) and day 12 (7%) were frequently observed days and two peaks were made by on days 3-4 and days 10-14. Fever on days 3 or 4 were observed in patients treated with erlotinib (29%), gemcitabine (19%), irinotecan (19%), docetaxel (18%), nedaplatin (13%), carboplatin (11%), and gefitinib (11%). The cause of fever was infection(45%) including neutropenic fever (23%), drug fever (25%), unknown (16%), tumor fever (7%). Conclusions: Fever on days 3 or 4 during cancer chemotherapy observed most frequently, and the frequency is differ between the chemotherapy agents. This fever seems to be watch as drug fever without use of antibiotics.
Loss of the Y Chromosome in Philadelphia-Positive Cells Predicts a Poor Response of CML Patients to Imatinib Mesylate Therapy.
Authors: Eric Lippert, Sophy Laibe, Marie-Joelle Mozziconacci, Carine Gervais, Stéphane Girault, Nathalie Gachard, Isabelle Tigaud, Nicole Dastugue, Francoise Huguet, Marie-Pierre Fort, Virginie Eclache, Francois-Xavier Mahon
Journal: Blood (2008)
Trastuzumab induced cardiotoxicity in HER2-positive metastatic esogastric cancers.
Authors: Jerome Martin-Babau, Yves Eusen, Cedric Verveur, Fanny Trouboul, Caroline Cheneau, Veronique Jestin Le Tallec, Helene Simon, Jean-Philippe Metges
Journal: Journal of Clinical Oncology (2016)

152 Background: Trastuzumab is widely used in Her2 positive metastatic esophageal and gastric cancers along with chemotherapy. Cardiotoxicity of trastuzumab has been described precisely in Her2 positive breast cancers and occurs with asymptomatic lowering of LVEF (Left Ventricular Ejection Fraction) in up to 10% of cases. Esogastric cancer patients are usually older and have more comorbidities than patients followed for breast cancer. Methods: This monocentric retrospective study measured the incidence of symptomatic and asymptomatic cardiotoxicity in patients treated for metastatic esogastric cancers and its potential impact regarding overall survival from October 2009 to September 2015. Patients should receive trastuzumab with chemotherapy during the period of study for treatment of Her2 positive metastatic esogastric cancer as first-line chemotherapy. Results: 27 patients received trastuzumab along with chemotherapy during the period of study. Median age was 62.3 years, sex ratio 21 M/6 W. The median number of cycles of trastuzumab was 5 cycles. The asymptomatic cardiotoxicity rate, defined by a drop of more than 10% of LVEF between the enrollment echocardiogram and the third month treatment echocardiogram, was of 22%. Symptomatic cardiotoxicity was observed in two patients (7.4%), with one cardiac failure and one myocardial infarction, with no associated death. Cardiovascular comorbidities and cardiac irradiation which is recurrent in this indication did not appear as a predictive factor of cardiotoxicity (p = 1). Overall survival of patients was not statistically modified by the occurring of cardiotoxicity even if we noted a trend to better outcome of the patients presenting an asymptomatic LVEF lowering. Conclusions: This study is to our knowledge the first to focus specifically on the cardiotoxicity of trastuzumab in esogastric metastatic Her2 positive cancer in the real world. These patients seem to be at a higher asymptomatic cardiac risk than breast cancer patients. However cardiovascular comorbidities didn’t appear as predictive factors of trastuzumab induced cardiotoxicity and should not prevent patient from benefiting of this treatment.
Wait time intervals for patients with prostate cancer in a multidisciplinary rapid diagnostic unit compared to a community-based referral pattern.
Authors: Perakaa Sethukavalan, Liying Zhang, Vibhuti Jethava, Christiaan Stevens, Stan Flax, Roger Buckley, Sue Bondy, D. Andrew Loblaw
Journal: Journal of Clinical Oncology (2013)

183 Background: Wait times in cancer diagnosis and treatment are important measures of how quickly patients are getting access to care. Prolonged wait times may affect a cancer patient’s treatment outcome, prognosis and quality of life. A previous study conducted in 2003 found the median wait time from suspicion of prostate cancer to radiotherapy (RT) was 247 days. The purpose of this study was to capture wait time intervals for patients referred to and treated with radical RT at the Odette Cancer Centre, comparing patients diagnosed in a rapid diagnostic unit (RDU) versus the usual community referral process. Methods: Patients were screened during RT planning for their newly diagnosed, biopsy-confirmed prostate adenocarcinoma. A semi-structured interview and chart abstraction was conducted in order to obtain the best estimation of key wait time milestones in the care pathway. Results: A total of 87 patients participated in the study: 44 RDU patients and 43 community patients. The median overall wait time interval from suspicion of prostate cancer to RT was 138 days for the RDU cohort and 183 days for the community cohort (p=0.046). There were statistically significant differences between the two cohorts, favouring the RDU cohort, for other key intervals, namely, suspicion to decision-to-treat (DTT; p=0.012), urologist to diagnosis (p=0.0094), diagnosis to DTT (p=0.018), and diagnosis to treatment (p=0.016). Among all patients, 25% perceived a delay in treatment and among those patients, 64% identified a systematic reason for the delay. There was no significant difference on the cause of delay between the RDU and community cohorts (p=0.86). Conclusions: Wait time intervals from suspicion to treatment are significantly shorter for prostate cancer patients in 2011-2 than in 2003 when diagnosed and referred in the community setting. A prostate-specific RDU further reduced wait time intervals supporting more multidisciplinary RDUs for common diseases. However, even in the RDU system, a minority of patients met provincial consensus-based wait time standards. Further work needs to be done to identify why delays are occurring and develop new processes to minimize delays.
The use of neoadjuvant chemotherapy plus molecular targeted-therapy in colorectal liver metastases: A systematic review and meta-analysis.
Authors: Dhanusha Sabanathan, Guy D Eslick, Jennifer Anne Shannon
Journal: Journal of Clinical Oncology (2015)

614 Background: Surgery remains the standard of care for patients with colorectal liver metastases (CLM) with a 5-year survival rate approaching 35%. Nordlinger et al. demonstrated perioperative chemotherapy confers a survival benefit in selected patients with CLM. The use of targeted molecular therapy in combination with neoadjuvant chemotherapy in CLM, however, remains controversial. We reviewed the literature of combination neoadjuvant chemotherapy and targeted molecular therapy on resectable and initially unresectable CLM. Methods: A literature search of databases (Medline and PubMed) was conducted to identify studies on neoadjuvant chemotherapy plus targeted molecular therapy in the management of resectable or initially unresectable CLM. We calculated pooled odds ratio (OR) and 95% confidence intervals (CI) using a random effects model for the relationship of combination neoadjuvant treatment on overall response rate and resectability rate. The analysis was stratified according to study design. Results: Ten studies were analysed, which included 828 patients that underwent systemic chemotherapy and molecular targeted therapy for CLM. Seven studies utilized cetuximab and three utilized bevacizumab. The use of combination neoadjuvant therapy was associated with an overall response rate of 73% (95% CI: 68-78%) and no heterogeneity was observed in the studies (I 2 =0.00, p=0.77). R0 resection rate after combination neoadjuvant therapy was 56% (95% CI: 25-82%), however, high levels of heterogeneity was observed (I 2 =94.02, p&lt;0.001). Overall median PFS was 13.7 months. Conclusions: Current evidence suggests that neoadjuvant chemotherapy in combination with molecular targeted agents in the treatment of CLM confers high overall response rates. Combination treatment may also significantly increase resectability rates in initially unresectable CLM. However these results have not translated into significant survival benefits. The role of targeted molecular therapy, with a focus on the molecular mechanism of action in the adjuvant versus metastatic settings, requires further research.