tbuckley/cabot-search huggingface dataset:
Pathologic response rates from neoadjuvant chemotherapy in muscle-invasive transitional cell carcinoma of the bladder.
Authors: W. P. Harris, E. Y. Yu, J. Shenoi, F. Lee, T. Champion, J. L. Wright
Journal: Journal of Clinical Oncology (2011)

e15181 Background: Neoadjuvant chemotherapy (NC) with MVAC for muscle invasive transitional cell carcinoma (TCC) of the bladder has been shown to improve survival, with pathologic complete response (pCR) serving as a robust predictor of survival benefit. While gemcitabine/cisplatin (GC) is often substituted in the neoadjuvant setting, positive randomized neoadjuvant data are available only for MVAC, and recent retrospective data have noted low pathologic complete response rates with GC. Methods: Data was retrospectively collected on 110 patients with T2-T4Nany TCC of the bladder who underwent radical cystectomy (RC) at the University of Washington Medical Center between September 2003 and July 2009. Information on clinical stage, neoadjuvant chemotherapy, comorbidities and pCR were collected. The prespecified primary endpoint was pCR rates comparing MVAC and GC neoadjuvant groups. Results: Of 110 patients, 43% received NC (total=47: GC=18, MVAC=12, dose dense MVAC=2, gem/carboplatin=7, other=8). Percentage of patients with advanced clinical stage at diagnosis as defined by T3 or greater or node positive was higher in patients administered NC and highest in those administered GC (any NC 43%, GC 72%, MVAC 50%, no NC 22%). pCR rates were significantly improved in patients undergoing NC versus surgery alone (28% vs. 12%, p=.03). No significant difference was noted in pCR rates (pT0) between GC and MVAC subgroups (33% vs. 17%, p=.31). When comparing rates of pCR allowing for residual in situ (pTIS) disease, NC provided superior response rates when compared with surgery alone (49% vs. 15%, p=.0001), and neoadjuvant GC provided superior response rates when compared to MVAC (67% vs. 25%, p=.025). Conclusions: Neoadjuvant chemotherapy for muscle invasive bladder TCC produced significantly increased pCR rates in comparison to surgery alone in patients who underwent RC at our institution. Interestingly, while there was no statistical difference in pathologic pT0 rates in the GC versus MVAC subgroups, when residual pTIS was allowed GC improved response rates over MVAC. These observations are in contrast to prior observations and support the use of GC as an alternative regimen in the neoadjuvant setting.
Poor performance status small cell lung cancer: Who should we treat?
Authors: F. Azam, H. Wong, J. A. Green, E. Marshall
Journal: Journal of Clinical Oncology (2011)

e17502 Background: Patients (pts) with poor performance status (PS) SCLC may experience symptomatic and survival benefits with chemotherapy (CT) but are at a greater risk of early treatment related death. Currently, there is no standard treatment policy for pts with the poorest PS and management may vary from best supportive care to single agent or combination CT. The aim of this study is to evaluate the treatment and survival of all SCLC pts with ECOG PS 3-4 presenting to a single UK Cancer Network. Methods: This is a retrospective analysis of all PS3 and 4 pts diagnosed with SCLC presenting from Jan 2005 to Dec 2009 at Merseyside and Cheshire Cancer Network. Data were prospectively recorded from the time of diagnosis using an electronic minimum data set. Results: A total of 246 SCLC pts presented with PS 3 (89%) or 4(11%). Median age was 71 yrs (38-91yrs), 125(51%) females and 121(49%) males, 212(86%) had extensive stage disease and 34(14%) had limited stage disease. The majority (67%) of pts did not receive any CT. Median survival for the whole group was 3 months (mo). Median survival for those who had CT was 6 mo (95% CI 3.70-8.29) compared to 2 mo (95% CI 1.71-2.28) in those who were not treated (p-value<0.01). 26% of pts who received CT died within 30 days of treatment. Median survivals for pts receiving platinum based combination CT (carboplatin and etoposide, N=41), single agent carboplatin (N=32) and oral Etoposide (N=7) were 8 mo (95% C.I 3.82-12.1), 5 mo (95% C.I 2.62-7.37) and 2 mo (95% C.I 1.21-2.78) respectively. Clinical factors for longer survival were female gender, limited disease, absent or single site visceral metastases, weight (wt) loss of less than 5% of total body wt and minimal co-morbidities. Factors predicting death within 30 days of diagnosis (N=63) were male gender, visceral metastases especially liver, more than 5% wt loss and significant co-morbidities. Conclusions: Overall survival remains poor in the poorest PS patients with a high incidence of treatment-related early death. However, subsets of patients with minimal co morbidities, weight loss of less than 5% body weight and small volume metastases appear to benefit from CT with improvement in survival and reduction in early death. The optimum regimen remains to be defined.
Objective physical activity and quality of life in breast and colon cancer patients after completion of adjuvant chemotherapy.
Authors: J. M. Walsh, J. M. Hussey, M. J. Kennedy, D. M. O' Donnell
Journal: Journal of Clinical Oncology (2011)

e19609 Background: To our knowledge, objective physical activity (PA) levels after completion of adjuvant chemotherapy have not been documented, despite inactivity being a risk factor for cardiovascular disease and possibly for cancer recurrence. We carried out a prospective, longitudinal study investigating objective and subjective PA and quality of life (QOL) in cancer patients 6 weeks (T0), 6 months (T1), and 12 months (T2) after the end of chemotherapy. Methods: PA was measured objectively using the RT3 accelerometer and subjectively using the International Physical Activity Questionnaire (IPAQ). QOL was evaluated with the EORTC-QLQ C30. Data was compared across time-points. Repeated measures ANOVA was used for normally distributed data and Friedman’s test for non-normally distributed data. BMI data was based on available recorded weight which correlated with PA measurement period (n=26 for T0 and n=25 for T2). Results: 29 patients with a mean age (±SD) of 51 (±17) years were recruited after completing adjuvant chemotherapy (25 breast, 4 colon). Cognitive function improved (p=0.005) by T1, fatigue (p =0.024), and appetite loss (p=0.048) were significantly better by T2. The table shows changes in objective PA over the study period. Subjectively measured PA remained stable over time; sedentary behavior was typically underestimated by 1 hour per day. Only 23.1% of subjects had a BMI of 25 or less at T0, and this decreased to 12% at T2. Conclusions: Despite improvements in fatigue and other chemotherapy-related QOL parameters in the year after treatment, objective PA levels failed to increase. Only 54% of patients were meeting minimum PA guidelines for health at 1 year and most were overweight or obese. Further investigation of the failure to improve PA and reinforcement of weight management advice and PA benefits are needed in cancer survivors. T0 T1 T2 Objective PA level (minutes)* 55.1 (±58.3) 43.6 (±44.9) 41.9 (±37.7) Subjects meeting minimum activity guidelines** 62% 48% 54% * Minutes in moderate and/or vigorous activity per day. ** At least 30 minutes of moderate and/or vigorous activity per day.
Looking Back at Look AHEAD Through the Lens of Recent Diabetes Outcome Trials
Authors: L. Maria Belalcazar, Christie M. Ballantyne
Journal: Circulation (2017)

ook AHEAD (Action for Health in Diabetes), the largest cardiovascular disease (CVD) outcomes trial of an intensive lifestyle intervention for weight loss in diabetes mellitus, was stopped on September 14, 2012, on the basis of a futility analysis of its composite primary end point (death from cardiovascular causes, nonfatal myocardial infarction [MI], nonfatal stroke, or hospitalization for angina) and recommendations from the Data and Safety Monitoring Board. 1 Its results have been widely interpreted as evidence that weight loss with lifestyle intervention does not confer CVD benefits in patients with diabetes mellitus.In contrast, recent trials of pharmacological antihyperglycemic therapies, EMPA-REG Outcome with empagliflozin (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), 2 LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) with liraglutide, 3 and SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes) with semaglutide, 4 demonstrated both weight loss and reduced cardiovascular morbidity and mortality.Before concluding that lifestyle modification does not provide cardiovascular benefit in patients with diabetes mellitus, whereas drug therapy does, it is important to examine closely the end points, participants, and interventions in Look AHEAD in comparison with those in the pharmaceutical trials (Table ).
Correlation between molecular features (MFs) and clinical results in endometrial cancer (EC): A single-institution experience.
Authors: J. M. Del Campo, V. Rodriguez-Freixinos, I. Diaz De Corcuera, G. Sánchez-Ollé, A. Gil-Moreno, R. Verges, A. Garcia, N. Mulet-Margalef, A. Perez-Benavente, D. Moreno-Fernandez, A. Vivancos, A. M. Oaknin
Journal: Journal of Clinical Oncology (2011)

e15572 Background: EC is the most common gynecologic tumor. Although overall survival (OS) is greater than 80%, a subgroup of patients (pts) has a poorer prognosis. Different MFs have been described in EC. PTEN loss and PIK3CA mutations (mut) are the most frequent up to 70%. Currently, there are paucity data of their clinical outcome influence. We have determined PTEN loss and PIK3CA mut in an EC pts cohort to correlate these findings with established prognostic factors and OS. Methods: Formalin-fixed paraffin-embedded tissue of 42 consecutive EC pts treated between 2001 and 2010 were obtained. PTEN loss expression (Hscore≤50) and PIK3CA mut were evaluated by inmunohistochemistry and Sequenom MassARRAY system respectively. Clinical and pathological data were reviewed from medical records. Statistical methods included univariate and multivariate analysis (Histological Type, Tumor grade, FIGO Stage and MFs). Results: A total of 42 pts were analyzed: 21 (50%) Type I (endometrioid) and 21 (50%) Type II (17 Serous-papillary and 4 clear cell) histology. Median age was 62 y (33-79). Sixteen (38%) and 26 pts (62%) were FIGO stage I-II and III-IV respectively. Thirty pts (77%) had grade 3 tumor. All pts but one were initially treated with surgery, 8 pts received adjuvant chemotherapy, 12 pelvic radiotherapy and 15 both. Regarding MFs, 17 pts (41%) had PTEN loss, 5 (12%) PIK3CA mut and 11 (26%) had both. Seven PIK3CA mut were identified, being R88Q the most frequent (31%). Molecular findings were balanced between early and advanced stages (80% and 81% respectively). Median OS was 41 m (27-56). Analyzing OS regarding clinical and molecular features, only the presence of PTEN loss and/or PIK3CA mut has a negative impact. An alteration in the PI3K pathway does not reached statistical significance for OS in the univariate (p=0.059) but it does in the multivariate model (p=0.025, CI 0.020- 0.765). Median OS was 33 m (16-50) and 45 m in the group with and without molecular changes respectively. Conclusions: In our EC cohort, OS is influenced by molecular changes in PI3K pathway reaching statistical significance. Although there could be a bias due to the sample size, our findings warrant further investigation.
Prognostic role of ER+ associated with other clinical and biological features in patients with T4 breast cancer achieving less than a pathological complete response (&lt;pCR) after primary chemotherapy: 10-year results.
Authors: M. T. Ionta, F. Atzori, M. C. Deidda, V. Pusceddu, E. Valle, M. Barca, A. Coinu, M. Murru, L. Minerba, B. Massidda
Journal: Journal of Clinical Oncology (2010)

e11047 Background: The achievement of pCR correlates with significantly better outcomes irrespective of common clinical prognostic factors. By contrast less than pCR (<pCR) identifies a heterogeneous group of patients (pts) at different risk of recurrence and death, being ER+ the subgroup with the best prognosis. Aim of our study was to evaluate the influence of baseline PgR, HER2, grade, age, inflammatory disease (T4d), postsurgical residual pT and pLN and type of primary regimen, on long-term DFS in ER+ T4 pts achieving <pCR. Methods: We analyzed 80 ER+ of 132 consecutive T4 pts <pCR after anthra-based (FEC, 29 pts) or anthra-cisplatin-based (cisplatin, epirubicin, vinorelbine, 51 pts) primary chemotherapy. All patients received the same adjuvant chemo-endocrine therapy; trastuzumab was not allowed; 32 pts (40%) were <50y; 18 (22%) T4d; 27 (34%) G3; 10 (12,5%) HER2+; 40 (50%) PgR+; 50 (62,5%) pT0-2; 30 (37,5%) pT3-4; 50 (75%) pLN+. DFS was analyzed using Cox proportional hazards ratios (HR). Results: After a median follow-up of 120 months (14-205 ), as expected 10 y DFS was better in ER+ group (80 pts) than in ER- (52 pts) (41% vs 25%; p=0.049). Among ER+ patients, HER2+, pLN+, T4d, anthra-based versus cisplatin-based primary chemotherapy, were associated with significantly poor DFS (HRs > 2). None of the other factors affected significantly the prognosis. Conclusions: Overall, ER+ status is predictor for better DFS in patients <pCR. The association with HER2+, pLN+, inflammatory disease and anthra versus anthra-cisplatin based primary chemotherapy, decreases the likelihood of DFS. These patients should be considered for innovative treatment in addition to chemo-endocrine therapy. ER+ HR IC 95% p value ER+ HR IC 95% p value PgR+/PgR- 1.16 0.66-2.1 0.60 HER2+/HER2- 2.07 0.89-4.82 0.09 G2/G3 0.79 0.42-1.49 0.47 T4abc/T4d 0.51 0.27-0.96 0.037 <50/≥50 0.82 0.46-1.46 0.50 pLN+/pLN- 2.56 1.08-6.03 0.032 pT0-2/pT3-4 1.32 0.74-2.36 0.35 anthra/cisplatin 2.07 1.07-3.98 0.030 No significant financial relationships to disclose.
Intraductal carcinoma and cribriform architecture as novel prognostic factors in patients with prostate cancer treated with dose-escalated radiotherapy.
Authors: Jure Murgic, Alejandro Berlin, Melvin Chua, Melania Pintilie, Robert G. Bristow, Theodorus van der Kwast
Journal: Journal of Clinical Oncology (2016)

101 Background: Intraductal carcinoma (IDC) and cribriform architecture (CA) represent distinct pathohistological variants of high-grade prostate cancer associated with aggressive disease and poor clinical outcome. We evaluated impact of IDC and/or CA (IDC/CA) as a prognostic marker in patients with prostate cancer who underwent contemporary image-guided, dose-escalated, intensity-modulated radiotherapy (IMRT). Methods: Radiotherapy and clinical records of 379 patients with localized prostate cancer treated from 2005 to 2012 with prostate IMRT with 78 Gy in 39 fractions were retrospectively reviewed. Original diagnostic prostate biopsy slides were centrally reviewed by an expert genitourinary pathologist and scored for presence of IDC/CA. The impact of IDC/CA and other pre-treatment and treatment-related factors on biochemical relapse-free survival (BRFS) was evaluated. Results: IDC/CA was present in 19.3% of patients. After median follow-up of 56 months, 39 (10.3%) and 10 (3.6%) patients experienced biochemical failure and distant metastasis, respectively. On univariate analysis, the presence of IDC/CA was associated with decreased BRFS (HR 4.1 (95% CI: 2.2-7.8), p &lt; 0.0001) and metastasis-free survival (HR = 4.7 (95% CI: 1.4-15.6), p = 0.013). On multivariate analysis, IDC/CA was associated with decreased BRFS (HR = 2.3 (95% CI: 1.2-4.7), p = 0.02) together with NCCN risk group (overall p = 0.0004), Gleason score (overall p = 0.016) and percent of positive biopsy cores (HR = 5.78 (95% CI: 1.4-23.9), p = 0.015). Within intermediate risk patients, presence of IDC/CA was associated with decreased BRFS (HR = 3.3 (95%CI: 1.5-7.1), p = 0.031) and was able to further stratify GS 4+3 patients (HR = 4.5, (95% CI: 1.6-13.0), p = 0.0045). Conclusions: The presence of IDC/CA in the prostate biopsy has negative prognostic impact in patients treated with dose-escalated radiotherapy. Furthermore, the prognostic significance of IDC/CA, even among unfavorable intermediate-risk patients, suggests that these pathological features should be considered in existing risk stratification tools for this patient group.
American medical oncology physician (AMOP) preferences for combined modality therapy beginning with systemic management in patients with liver-limited metastatic colorectal cancer (LL-mCRC).
Authors: Michael A. Choti, Mark R. Green, Mitra Corral, Schiffon L. Wong, Jessica Cairns, Michele R. Thomas, Michael Eaddy
Journal: Journal of Clinical Oncology (2013)

532 Background: Patients with LL-mCRC are frequently managed with multi-modality therapy, including systemic chemotherapy ± biotherapy. In some settings, surgery is used first followed by systemic therapy. In others, the systemic therapy may be used for initial cytoreduction of both macro- and micro-metastatic disease with surgical consolidation and then observation or further systemic management post-operatively. In the current study, we assessed the preferences of 190 AMOPs in the treatment of patients with LL-mCRC. Methods: AMOPs practicing for ≥5 years and ≤35 years with ≥70% direct patient contact were eligible for study inclusion. To assess preferred sequencing, a single patient profile was created and 10 different sets of de-identified liver CT l images representing a broad spectrum of LL-mCRC were collected. AMOPs independently reviewed each set of liver CT images through a web-based tool and provided their assessment of the immediate resectability of the LL-mCRC shown, as well as their preferred approach to the initial management for that set of scans. Treatment preferences across all scans were presented according to the percentage of AMOPs designating a particular scan as resectable now. Results: Participating AMOPs treated an average of 15.5 mCRC patients per month. Resectability rates and preferences for initial therapy are shown in the Table. Conclusions: AMOPs show an overall preference for initiation of sequencing multi-modality management with systemic therapy across the spectrum of LL-mCRC. [Table: see text]
The relationship between the expression of VEGF and survivin and the inhibitory effect of endostar combined with radiotherapy on transplanted tumor model.
Authors: X. Xiaoting
Journal: Journal of Clinical Oncology (2011)

e21017 Background: Radiation therapy resulted in elevated expression of vascular endothelial growth factor (VEGF) which might contribute to the resistance against radiation in tumors. Therefore, we speculated that radiation therapy combined with antiangiogenic therapy might be potent to decrease radiation resistance. This study was to observe the inhibitory effect of Endostar combined with radiotherapy on transplanted CNE1 nasopharyngeal carcinoma (NPC) in BALB/c nude mice and explore the relationship of this inhibitory effect with the expression level of VEGF and apoptosis inhibiting protein, survivin. Methods: The transplanted tumor model of human CNE1 nasopharyngeal carcinoma on nude mice was established to evaluate the antitumor activity of Endostar combined with radiation (Endostar + radiation) treatment compared with monotherapy (Endostar or radiation). The growth characteristics of transplanted tumor were recorded. Transmission electron microscopy and flurescence microscopy were used to observe the morphological changes of cell apoptosis. Real-time quantitative PCR was used to determine the effect on VEGF and Survivin mRNA expression level of of tumor tissues. Results: Significant on the tumor growth was found in Endostar + radiation group. More typical morphological changes were seen in cancer cells in Endostar + radiation group. Level of VEGF in tumor tissue of Endostar + radiation group was lower than that of radiation or control (P<0.05). And the level of Survivin in Endostar + radiation group were much lower than in other three groups (P<0.05). The results of linear Correlation relevant analysis showed that there exist positive correlation between the inhibitory effect and the expression of VEGF and Survivin (r = 0.679, P < 0.01). Conclusions: Endostar could enhance the radiosensitivity of NPC transplantation tumor in nude mice to radiation. The mechanism may be down-regulating the expression of VEGF and Survivin.
Evaluation of leukocytosis: Benign or malignant.
Authors: Elizabeth Ann Bowhay-Carnes, Shuko Lee, Paromita Datta
Journal: Journal of Clinical Oncology (2016)

245 Background: Hematologists frequently evaluate patients with leukocytosis to differentiate between benign and malignant causes. The objective of this quality improvement project was to identify risk factors for malignant leukocytosis. Methods: A retrospective analysis of 1,330 consults in ALM VA Outpatient Hematology Clinic between 1/1/2011 and 2/22/2015 was performed. 147 patients referred for evaluation of leukocytosis were included in this study. The following data was collected: sex, age, race, ethnicity, BMI, tobacco use, total WBC, tempo of leukocytosis (constant vs intermittent), Hg level, plt count, ANC, ALC, AMC, AEC, ABC, laboratory tests performed during work-up, final diagnosis (primary hematologic malignancy vs secondary causes). 35 patients (24%) with a diagnosis of primary hematologic malignancy were compared with 112 patients (76%) with secondary causes and the relative risk of a primary hematology malignancy related to various risk factors was calculated. Results: See Table. Conclusions: Statistically significant independent risk factors for the presence of a primary hematologic malignancy as the cause of leukocytosis were identified. There was no increased risk based on race, ethnicity, BMI, AMC, or AEC. By identifying risk factors for malignant leukocytosis, we have created and implemented an algorithm outlining clinically appropriate and cost-effective laboratory evaluation for patients with leukocytosis.[Table: see text]
Development of a quality infrastructure for a 135-site statewide network of community oncologists.
Authors: Gay Lindsey, J. Russell Hoverman
Journal: Journal of Clinical Oncology (2012)

74 Background: The delivery of patient centered, high-value care requires a formal system of continuous quality improvement. In order to bring metrics to the site and physician level the need to revamp our program for 364 physicians was apparent The starting point was 4 physician-led network wide quality committees. Methods: In 2010, the position of Director of Quality Programs was created to assist in the development of a quality infrastructure for a statewide network of community oncologists. Beginning in January 2011 meetings were held with the management team of each site for education on national quality initiatives and the IOM 6 aims for improvement in healthcare. The discussion also included review of quality metrics set forth by ASCO’s QOPI, evidence-based pathway reporting, variance reporting on patient safety and employee safety, and processes to improve patient satisfaction. Each site then identified their team members, physician champion, and frequency of committee meetings. An action plan format was provided with discussion on components of the plan and the reporting structure to the physician-lead quality oversight committees. Results: The network currently has 38 quality committees serving 84 sites of service. Within a year’s time pathways assessable data improved from 84% to 90%, pathways adherence improved from 60% to 68%, and exception documentation rose from 14% to 25%. Variance reporting increased 35% and a network Patient Satisfaction Survey was created and administered with 10 surveys per physician collected and tabulated for baseline data. The survey process was reviewed and refined and will now be administered twice yearly at each site. Documentation of hospice referrals and follow-up processes on deceased patient information are key initiatives at each site. Conclusions: Development of a robust quality infrastructure at the site level can increase adherence to quality measures by identifying common barriers to improvement, sharing of best practices, and supporting the delivery of patient-centered, value-based care.