tbuckley/cabot-search huggingface dataset:
Using patient-reported outcomes to assess the effectiveness of topical hormonal replacement therapy (THR) for vaginal complaints (VC) after anti-hormonal therapy (HT) treatment for breast cancer (BC).
Authors: Omer HASSAN Jamy, Namratha Reddy Vontela, Justin Gatwood, Mark Stephen Walker, Edward J. Stepanski, Gregory A. Vidal
Journal: Journal of Clinical Oncology (2016)

77 Background: THR is sometimes used for treatment of VC in BC patients previously treated with HT. The safety of this practice remains a question but the effectiveness of this strategy has not been reported. Methods: We conducted a retrospective analysis of patient reported symptoms at the West Cancer Center (WCC) between 2002 and 2014. Early stage BC patients previously treated with HT with reported VC ± THR were statistically matched 1:1 using propensity score matching with calipers of 0.01. Demographics and clinical characteristics were extracted from electronic records and a proprietary patient-reported outcomes database: the Patient Care Monitor (PCM). A baseline PCM score for vaginal dryness and sexual dysfunction was noted at the initiation of THR and was followed for 12 months. Univariate statistics compared the resulting cohorts and repeated measures ANOVA assessed the impact of topical therapy. Results: We compared 74 THR patients to 74 controls (Table). The mean reported symptom scores were 3 fold higher in the active group with no statistical improvement in symptom scores noted at 6 or 12 months (Table). At the WCC, of the 5,479 patients with VC analyzed, only 5% received THR. The study was underpowered for survival analysis. Conclusions: In our study, increased severity of VC was associated with increased use of THR. However, there is no evidence that THR was effective in alleviating symptoms of vaginal dryness or sexual dysfunction. [Table: see text]
Phosphorylated AMP-activated protein kinase and MAPK3/1 expression associated with prognosis for patients with gastric cancer.
Authors: Jong Gwang Kim, Yee Soo Chae, Byung Woog Kang, Yoo Jin Lee, Min Chan Kim, Ki Han Kim, Su-Jin KIm
Journal: Journal of Clinical Oncology (2013)

36 Background: Phosphorylated AMP-activated protein kinase (pAMPK) has central roles in cellular metabolic sensing and energy balance homeostasis, and interact with various pathways [e.g., TP53, MTOR, NUAK2 (sucrose nonfermenting-lkie kinase), MAPK3/1(ERK), and PDK (pyruvate dehydrogenase kinase)]. The present study analyzed the expression of pAMPK, NUAK2, MAPK3/1, and PDK-1 and their impact on the survival of patients with resected gastric cancer. Methods: Six hundred and twenty-one patients with surgically resected gastric adenocarcinoma with curative intent were enrolled in the present study. Immunohistochemical staining for pAMPK, NUAK2, MAPK3/1, and PDK-1 was performed using tissue microarrays of operative specimens of gastric cancer. The expressions were divided into two or three groups according to the intensity score [pAMPK: negative (0), weak to intermediate positive (2), strong positive (3); NUAK2: negative (0), positive (2); MAPK3/1: negative (0), focal positive (2), diffuse positive (3); PDK-1: negative (0), positive (2)]. Results: Positive pAMPK, NUAK2, MAPK3/1, and PDK-1 expression was observed in 379 (61.0%), 257 (41.4%), 327 (52.7%), and 67 (10.8%) cases, respectively. Multivariate survival analysis showed that the survival for the patients with negative expression of pAMPK was worse than for the patients with the weak to strong positive expression [disease free survival (DFS): hazard ratio (HR)=1.361, P=0.029), and the negative expression of MAPK3/1 was also associated with a worse survival compared to the positive expression (DFS: HR=1.401, p=0.029). Conclusions: pAMPK and MAPK3/1 expressions were found to be an independent prognostic marker for patients with gastric cancer. Accordingly, the analysis of pAMPK and MAPK3/1 expression can help identify patient subgroups at high risk of a poor disease outcome.
Making treatment decisions at end of life in a comprehensive cancer center.
Authors: Anna Catherine Beck, Lee Ellington, Kathi Mooney
Journal: Journal of Clinical Oncology (2016)

51 Background: End of life treatment decisions are challenging for cancer patients and oncology providers. Patients must understand their prognosis and options, deciding if and when to increase palliative care and decrease tumor-focused therapy. Cancer centers committed to offering clinical trials and evaluate new therapies add complexity to these decisions. To better define crucial points for decision making, we reviewed the care patients received during the last 6 months of life at one comprehensive cancer center. Methods: A retrospective chart review was conducted of the 301 cancer patients who died during one calendar year and were treated at the Huntsman Cancer Institute. We abstracted the care documented from all clinic visits, phone calls and hospitalizations including referrals and resources utilized during the last 6 months of life. Results: Men and women were equally represented with a mean age of 61at death and a median survival of 13 months after diagnosis. Over 1780 outpatient visits were documented during the last 6 months of life with treatment decision conversations noted at 68% of visits. Results of these discussions included new chemotherapy initiated at 26% of visits, treatment termination at 19% of visits, palliative therapy only at 9% of visits, and no treatment change at 47% of visits. Of the 64% of patients receiving chemotherapy in the last 6 months, 32% continued therapy in the last 30 days of life. Similarly, 34% of patients received radiation therapy in the last 30 days. Hospice was used by 59% of patients, with a mean length from referral to death of 29 days. Conversations about hospice occurred in 65% of patients with a mean/median of 2 conversations/patient. Approximately 37% of these conversations resulted in hospice enrollment, 49% deferred a decision and in 14% the patient requested additional treatment. Conclusions: Defining optimal timing for stopping cancer directed therapy is challenging in medical and radiation oncology, with 1in 3 patients continuing treatment in the last month of life. Goals of care and hospice conversations were required on multiple occasions, underscoring the need for oncology providers to have highly honed communication skills to minimize futile care and maximize palliative care.
Prognostic factors affecting severity of radiation-induced fibrosis.
Authors: Ahmed M Maklad, Hanan Abdel-Rady Assaf, Essameldin Abdelaziz Nada, Ashraf Elyamany, Asmaa A Badran
Journal: Journal of Clinical Oncology (2016)

e280 Background: Evaluation of prognostic factors affecting Radiation Induced Fibrosis (RIF) to help for decreasing its incidence and to improve quality of life for cancer survivors. Methods: Thirty patients were included in this study .It was carried out at faculty of medicine, Sohag University Hospital, Egypt during the period between July 2012 and July 2013 after approval of university ethical committee. We included all patients with (RIF) which is persistent or appeared after 6 months of completion of radiation therapy. Detailed medical history and clinical examination were done for all patients included in the study. We categorized the patients according to severity of RIF into four grades according RTO 2010. Assessment of pain was done according to 0–10 Numeric Pain Rating Scale. Results: Thirty patients with RIF were included in the study. The age of the studied patients ranged from 21- 65 years with a Mean 48,33 ± SD of 10,88. 56.7% of the cases were more than 50 years old. Female patients were 73.3%. BMI of the studied patients ranged from 19-40 kg/cm2 with a Mean 28.03 ± SD of 6.98. 26.7%patients were smokers.43.3% patientshadprevious history of acute radio dermatitis.60% had breast tumor. Chest was affected in 19 (60%) patients, back in 3 (10%) patients, neck in 4 (13%) patients, lower limbs in 2 (7%) patients, and face in 2 (7%) patients.T1 represented in 30%, T2 in 36.7%, T3 in 13.3% while T4 in 20% of the included patients. Twenty four (80%) patientsreceived chemotherapy before radiation. We documented a significant relation between BMI and severity of RIF (p = 0.007).Severity of RIF was significantly associated with higher BMI (p = 0.007), higher radiation doses (p = 0.02), higher number of radiotherapy treatment fraction (p = 0.03), higher radiation field sizes (p = 0.003), and patients with duration of more than one year of RIF (p &lt; 0.001). Patients from rural areas documented higher degree of RIF (p = 0.03). Conclusions: It is important to give more attention to RIF as a one of late toxicity of radiation therapy. It can be minimized by avoiding its predisposing factors to improve quality of life of cancer survivors.
SWOG S1007: A phase III, randomized clinical trial of standard adjuvant endocrine therapy with or without chemotherapy in patients with one to three positive nodes, hormone receptor (HR)-positive, and HER2-negative breast cancer with recurrence score (RS) of 25 or less.
Authors: A. M. Gonzalez-Angulo, W. E. Barlow, J. Gralow, F. Meric-Bernstam, D. F. Hayes, C. Moinpour, S. D. Ramsey, A. F. Schott, D. B. Sparks, K. S. Albain, G. N. Hortobagyi
Journal: Journal of Clinical Oncology (2011)

TPS104 Background: Multi-gene tumor assays have provided clinically useful prognostic information for patients with HR receptor and node-positive breast cancer. The 21-gene RS was shown to be prognostic for patients treated with tamoxifen alone, and exploratory studies suggested that it may be predictive of benefit from chemotherapy. In retrospective analyses from S8814, patients with low RS appeared to get no benefit from adjuvant CAF chemotherapy, while those with higher RS did. These retrospective data require validation, especially since more modern chemotherapy might be more effective than the regimen used in S8814. In January 2011 SWOG activated a trial to test the efficacy of using modern chemotherapy regimens in node positive patients with low RS, whose prognosis is still moderately poor but may not benefit from adjuvant chemotherapy based on tumor biology predicted by the RS value. The trial is similar to the Tailor RX study, but focuses on a node-positive population with low and intermediate RS. Methods: Phase III randomized clinical trial of best endocrine therapy vs. best endocrine therapy and chemotherapy. Patients with 1 to 3 positive lymph nodes, HR-positive and HER2-negative invasive breast cancer with RS ≤ 25 are eligible for randomization. Approximately, 9,400 patients will be screened to randomize 4000, stratified by RS (0-13 vs. 14-25), menopausal status, and axillary surgery (sentinel node vs.full dissection). Patients will be informed of their RS. Trial is powered on finding a significant interaction of treatment assignment and the continuous RS value and subsequently deriving a cutpoint for using the assay to guide treatment decisions. Patients who consent to screening are required to consent to banking of the tumor tissue and blood for further studies. Patient Reported Outcomes will be collected pre, post screening and post-randomization. The study also has a cost-effectiveness analysis. Status: Open nationwide through participating NCI-funded cooperative groups. NCT01272037.
Development time of trial protocols in the Japan Clinical Oncology Group (JCOG).
Authors: A. Kimura, K. Nakamura, T. Shibata, J. Mizusawa, I. Saito, A. Takashima, H. Katayama, F. Kunieda, K. Kanato, S. Matsubara, H. Fukuda
Journal: Journal of Clinical Oncology (2011)

e16568 Background: Protocol development process consists of multiple steps and takes considerable amount of time, and it is regarded as one of barriers for timely trial completion. Streamlining of protocol development has been one of the major concerns worldwide today. Dilts et al. reported that median calendar days to activate phase III trial are 784 in CALGB (JCO 2006), 808 in ECOG (Clin Cancer Res 2008), and 602 in all CTEP-sponsored trials (JCO 2009). We studied protocol development time of the trials conducted by JCOG and explored possible solutions for streamlining protocol development. Methods: An analysis for protocol development time was conducted on all JCOG trials activated between 2000 and 2010. Protocol development time was the calendar time from concept approval by JCOG Executive Committee to final protocol approval by JCOG Protocol Review Committee. Association between “fast/slow,” divided by median, and trial characteristics were investigated by both univariate comparison and multivariate logistic regression analysis. Results: The median protocol development time was 573 days in 69 trials (range: 222 to 2,413 days). The results of subset analyses are shown in the table. Variability was remarkable among disease subgroups and year of concept approval. Odds ratio (OR) in multivariate logistic regression model was significant only in disease subgroups (faster in gastrointestinal group). Conclusions: Unfavorably, it took longer time in phase II trials than in phase III trials, and more time may have been needed to reach agreement on protocol treatment among investigators in phase II. To reduce intergroup difference, more aggressive promotion of sharing know-how in faster disease group may be necessary. Protocol development time by trial characteristics. N Median (days) Year of concept approval 2000-2001 17 551 2002-2003 17 432 2004-2005 15 879 2006-2007 12 697 2008-2009 8 481 Phase II 18 690.5 III 32 533.5 Modality Chemotherapy alone 23 573 Radiotherapy included 14 481 Chemoradiotherapy included 7 752 Surgery included 28 578.5 Group Gastrointestinal groups 30 519.5 Lung groups 14 598.5 Other disease groups 25 653
Feasibility, acceptability, and efficacy of a proactive telephone intervention to improve toxicity management during chemotherapy.
Authors: Monika K. Krzyzanowska, Cassandra McKay, Heekyung Han, Sonal Gandhi, Nicole Beatrice Laferriere, Clare Atzema, Kelvin K. Chan, Doris Howell, Vishal Kukreti, Yvonne Leung, Aliya Pardhan, Sandy Mitchell, Marla Nayer, Mark Pasetka, Jane Yao, Erin Redwood
Journal: Journal of Clinical Oncology (2016)

105 Background: Chemotherapy (chemo) is associated with a significant risk of toxicity, which often peaks between ambulatory visits. Consequently, effective remote symptom management support is essential to optimize self-management and resource use, including emergency department visits and hospitalizations (ED+H) during chemo. The aim of this study was to examine the feasibility, acceptability and effects of a telephone management intervention on symptomatic toxicity and resource use during chemo for early stage breast cancer (EBC). Methods: A prospective study of telephone-based toxicity management among women receiving neo-adjuvant or adjuvant chemo for EBC was undertaken at one urban and one rural site in Ontario, Canada. The intervention consisted of two standardized calls by nurses assessing common toxicities after each chemo (call 1 within 3 days and call 2 within 8-10 days). Primary outcome measures were feasibility and acceptability based on patient (pt) and clinician feedback. Efficacy was evaluated by self-reported ED+H. Results: Between 09/2013 and 12/2014, 77 women with EBC were enrolled (mean age 55 years). Most commonly used regimens were AC-paclitaxel (58%) and FEC-docetaxel (16%). 78% of pts received primary GCSF prophylaxis. Adherence with calls was 82%; mean call duration was 9 minutes. The intervention was well received by both pts and clinicians. 97% of pts indicated they liked receiving the calls and 94% would recommend this protocol be offered to all pts receiving chemo. Clinicians and pts felt the calls reduced pt anxiety by providing just-in-time education and counselling. Twenty five (33%) pts reported at least one ED+H during chemo, lower than the historical rate of 44% for this population in Ontario. Challenges included introducing an intervention that involved both routine clinical personnel and research staff and incorporating the calls into existing work responsibilities. Conclusions: Telephone-based toxicity management during ESB chemo is feasible, perceived as valuable by clinicians and pts, and may be associated with lower rates of acute care use. Larger scale evaluations of this approach focusing on effectiveness are warranted.
Phase I study of a combination therapy of gemcitabine and candesartan in patients with advanced pancreatic cancer: GECA-1 study.
Authors: Y. Nakai, H. Isayama, H. Ijichi, T. Sasaki, H. Yagioka, H. Kogure, K. Kawakubo, N. Yamamoto, N. Sasahira, K. Hirano, M. Tada, K. Koike
Journal: Journal of Clinical Oncology (2011)

e14555 Background: Increasing evidence indicates a role of the local rennin-angitensin system (RAS) in tumor growth, suggesting potential of RAS as a target for cancer treatment. Our retrospective analysis showed inhibition of RAS was associated with better progression-free survival and overall survival in patients with advanced pancreatic cancer receiving gemcitabine (Br J Cancer. 2010;103:1644-8). This study was conducted to investigate the maximum-tolerated dose (MTD) of candesartan, an angiotensin receptor blocker, in combination with gemcitabine in patients with advanced pancreatic cancer (UMIN-CTR 000002152). Methods: Candesartan was administered orally at escalating dose (4 mg, 8 mg, 16 mg and 32 mg) qd daily and gemcitabine was administered 1,000 mg/m2 30min i.v. day 1, 8, 15, repeated every 4 weeks. There were no dose escalations within each patient. Eligible criteria were unresectable locally advanced or metastatic pancreatic cancer without any prior treatment, ECOG PS 0-2, normal renal function and without hypertension or hypotension. DLT was defined as grade 4 hematological toxicities, Grade 2 hypotension, abnormal creatinine or potassium and grade 3 or 4 other non-hematological toxicities. MTD was defined when 2 or more patients in a cohort of 3 patients or when 3 or more patients in a cohort of 6 patients experienced DLT. Results: Between July 2009 and Oct 2010, 14 patients (4 mg: 3 patients, 8 mg: 3 patients, 16 mg: 6 patients, 32 mg: 2 patients) were enrolled in this trial. The median age, 60, male:female, 5:9, PS 0:1, 8:6, locally advanced, 43%. One of 6 patients at 16 mg demonstrated DLT of grade 4 neutropenia and 2 of 2 patients at 32mg demonstrated DLT of grade 2 hypotension. Tumor response by RECIST was SD in 11, PD in 1, and NE in 2. Response rate was 0% but disease control rate (DCR) was 79%. Median progression-free survival (PFS) was 8.1 months and 1-year survival was 65% after a median observational period of 9.8 months. Conclusions: The recommended dose of candesartan in combination with gemcitabine was 16 mg. The results of DCR and PFS appeared promising.
Impact of pelvic lymph node dissection during radical prostatectomy on 30-day post operative complications: Results from a large national database.
Authors: Nicola Pavan, Samarpit Rai, Nachiketh Soodana-Prakash, Raymond R Balise, Maria Carmen Mir, Bruno Nahar, Chad Ritch, Dipen Parekh, Mark L. Gonzalgo
Journal: Journal of Clinical Oncology (2016)

238 Background: Pelvic lymph node dissection (PLND) during radical prostatectomy (RP) is the most effective method for detecting lymph node metastases in patients with prostate cancer. The association between PLND during RP and morbidity, especially thromboembolic adverse events (AEs), remains unclear. We assessed the effect of PLND on 30−day postoperative AEs in patients undergoing RP using the American College of Surgeons’ National Surgical Quality Improvement Program database (NSQIP). Methods: A total of 21,895 men undergoing RP between 2006 and 2013 were classified into two groups according to surgical approach (MIS−RP vs. ORP) and whether PLND was performed. Multivariate logistic regression adjusting for approach and demographic features was performed to assess the impact of PLND for predicting two primary endpoints (overall complications and major complications defined as Clavien−Dindo ≥ 3) and for 17 types of complications. P−values were adjusted to maintain an experiment−wise p &lt; 0.05. Results: MIS−RP and ORP was performed in 17,354 (79.3%) and 4,541 (20.7%) patients, respectively. PLND was performed in 7,579 (43.7%) and 3,597 (79.2%) patients in the MIS−RP and ORP groups, respectively. The overall postoperative complication rate was 8.7% (5.5% for MIS−RP and 21.0% for ORP). PLND was not associated with a higher risk of DVT (OR 0.99; p= 0.98) or PE (OR 1.02; p= 0.91). However, PLND was associated with a higher risk of superficial surgical site infection (OR 1.68; p = 0.013), organ space surgical site infection (OR 1.77; p = 0.02), and perioperative transfusion (OR 1.32; p = 0.002) regardless of surgical approach. PLND was not associated with overall or major AEs on multivariable analysis. ORP was associated with a significantly higher risk of overall (OR 4.64, p &lt; 0.0001) and major (OR 1.6, p = 0.0004) AEs compared to MIS−RP. Conclusions: PLND during RP is associated with a significantly increased risk of certain types of AEs within the 30−day post−operative period. However, there appears to be no significant association between PLND and thromboembolic AEs.
Correlation between overall survival and other efficacy endpoints in advanced biliary tract cancer: Literature-based analysis from 13 randomized trials of first-line chemotherapy.
Authors: Toshikazu Moriwaki, Shinji Endo, Yoshiyuki Yamamoto, Takeshi Yamada, Akinori Sugaya, Mariko Kobayashi, Ichinosuke Hyodo
Journal: Journal of Clinical Oncology (2014)

352 Background: Chemotherapy for advanced biliary tract cancer (ABC) has progressed. Now gemcitabine plus cisplatin combination is considered the standard 1st-line treatment based on the results of many randomized studies. However, the impact of various efficacy parameters on overall survival (OS) remains unclear. Methods: We searched PubMed database with the key words of (“biliary tract neoplasms” or “bile duct neoplasms” or “gallbladder neoplasms” or “cholangiocarcinoma” [All fields]) AND (“chemotherapy”[All fields]) AND Clinical trial [ptyp] between Apr 1984 to Jun 2013 and abstracts presented at the meetings of ASCO/Gastrointestinal Cancers Symposium (2004–2013) and ESMO/WCGC (2002–2013). Then we identified randomized trials of 1st-line chemotherapy for ABC, and analyzed the relations between the results of OS and those of progression-free survival (PFS) or time to progression (TTP), response rate (RR), disease control rate (DCR), post-progression survival (PPS = median OS − median PFS/TTP), and the proportion of patients who received 2nd-line chemotherapy (%2nd). Results: Among 329 papers/abstracts retrieved, 13 randomized trials, 26 treatment arms of first-line chemotherapy for ABC were identified. Number of trials with information on median OS, median PFS/TTP, hazard ratio (HR) for OS and PFS/TTP, RR, DCR, and %2nd were 13, 13, 6, 13, 12, and 7, respectively. The analysis of all these trials demonstrated the median values (range) of OS, PFS/TTP, HR of OS, HR of PFS/TTP, RR, DCR, PPS, and %2nd were 9.4 (4.6–13) months, 5.3 (2.7–8.5) months, 0.71 (0.39–0.93), 0.65 (0.44–0.85), 20 (7.1–36) %, 67 (21–87) %, 4.0 (1.0–7.6) months, and 41 (15–79) %, respectively. Spearman rank correlation coefficient of differences (Δ) OS with ΔPFS/TTP, ΔRR, ΔDCR, and ΔPPS were 0.66, − 0.07, 0.66, and 0.34, respectively. The correlation coefficient between HRs for PFS/TTP and OS was 0.60. The correlation coefficient between ΔPPS and Δ%2nd was − 0.15. Conclusions: OS was moderately associated with PFS/TTP and DCR.