tbuckley/cabot-search huggingface dataset:
KI 67 in patients (pts) with breast cancer (BC) younger than age 35: A comparison with older patients treated in a single institution.
Authors: F. Vasseur, M. Baranzelli, C. Fournier, J. Bonneterre
Journal: Journal of Clinical Oncology (2011)

e21003 Background: The prognosis of pts 35 years of age or less is very poor. We studied a cohort of pts treated in the same institution for primary breast cancer. The aim of the study was to compare KI67 as well as histoprognostic grading (SBR), mitotic index (MI), estradiol, progesterone receptors (ER, PR) and HER2 according to age. Methods: 43 pts less than 35 years old were treated between January 1, 2006 and December 31, 2008 and 359 pts more than 35 years treated in 2006. Biomarker studies were performed on surgical specimens or tumor biopsy if neoadjuvant chemotherapy was performed. All pathological studies were performed in the same laboratory. Results: Young pts have a higher median value of KI67 (30% [3-95] vs 10% [0-90], p< 0.0001), more frequent grade 3 carcinoma (44% versus 28%, p=0.04) and higher grade 3 MI (35% vs 13%, p<0.001). Positive ER was observed in 56% of tumors in young pts vs 87% (p< 0.001), Positive PR in 38% vs 68% (p<0.001). Moreover, the Immunohistochemistry intensity was lower in young ptrs: 50% of high intensity for the ER vs 74% in older pts (p=0.02). Intensity was similar for PR :60% vs 62% respectively (p=0.87). HER2 wa more frequently amplified in young pts (24% vs 10%, p=0.007). Finally, young pts had more frequently a triple negative tumor (31% vs 8%, p<0.001). In this subgroup, young pts had a higher median Ki67 (70 [10-95] vs 38 [2-80], p=0.06) but grade 3 and MI were similar (67% of grading 3 vs 81%, p=0.34 and 50% of MI 3 in the two populations). Conclusions: Pts less than 35 years have more frequently high KI 67 values, grade 3 tumors, high MI, negative or poorly positive hormone receptors. Furthermore, they are more frequently HER2 positive.
When and How to Treat Subthreshold Depression
Authors: Kurt Kroenke
Journal: JAMA (2017)

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Comorbidity and survival of prostate cancer D3 patients
Authors: J. Cogswell, S. Badin, T. L. Oliphant, D. Hoover, V. T. Chang, M. L. Gonzalez, S. K. Gounder, L. Duque, S. Srinivas, B. S. Kasimis
Journal: Journal of Clinical Oncology (2008)

20668
A phase II study of VEGF trap in patients with radioactive iodine (RAI)–refractory thyroid carcinoma.
Authors: E. J. Sherman, A. L. Ho, S. Haque, R. M. Tuttle, R. A. Ghossein, H. Schöder, M. S. Baum, K. Kelly, A. P. Chen, A. R. Shaha, D. G. Pfister
Journal: Journal of Clinical Oncology (2011)

5566 Background: Several multi-targeted tyrosine kinase inhibitors (TKIs) have activity in RAI-refractory thyroid; anti-tumor effect attributed at least in part to their ability to inhibit angiogenesis in these vascular tumors. VEGF Trap (VT) is a recombinantly-produced fusion protein consisting solely of human sequences for vascular endothelial growth factor receptors 1 and 2 (VEGFR-1 and VEGFR-2) extracellular domains and human immunoglobulin IG1.VT has a good rationale for study in RAI-refractory thyoid cancers, and allows for a a more precise assessment of the role of angiogensis inhibition as a treatment strategy in these tumors. Methods: The study was a single institution, phase II, Simon 2-stage design [21->41 patients (pts)] based on objective response rate/6 month progression-free survival as the primary endpoints. Eligible pts have progressive, RAI-refractory/fluorodeoxyglucose (18-F)-avid, recurrent/metastatic, non-medullary, non-anaplastic thyroid cancer; RECIST measurable disease; and adequate organ/marrow function. VT 4 mg/kg IV was administered every 14 days. Accrual occurred 8/22/08 - 8/19/10. Data cutoff date is 1/14/11. Results: 41 pts were enrolled. One pt withdrew consent and never started treatment and is not included in the analysis. Demographics: female-53%; median age-66 years; histology-papillary (24)/follicular (2)/Hürthle (11)/poorly differentiated (3). Grade 4-5 adverse events at least possibly related to drug: grade 5 - none: grade 4 - proteinuria (3 pts); pain, thrombotic microangiopathy, cerebrovascular ischemia, duodenal hemorrhage, confusion/posterior reversible encephalopathy syndrome, myocardial infarction, and fatigue (1 pt each). Evaluation of best response: complete/partial (MR) (0); stable disease (33); progression (7). 15/33 pts with stable disease remained on study for > 6 months, 5/33 pts for > 12 months; the median duration of stable disease on treatment is 126 days (1-724 days). Conclusions: Unlike TKIs which have shown MRs in this setting, there have been no MRs seen with single-agent VT to date. However, stable disease lasting 6 months or more is common and toxicity is manageable. Study funded by grant N01 CM 62206.
Prospective study to evaluate impact of support group participation in women with gynecological cancer.
Authors: Andrea Garrick, Adam Pyrzak, Jeff Campbell, Bunja Jane Rungruang, Ramses F. Sadek, Sharad A. Ghamande
Journal: Journal of Clinical Oncology (2015)

243 Background: Unlike breast cancer support group literature, there is no data in women with gynecologic cancers who have different perspective about their disease and therapy. We have a well-established (10 years old) active grass root level support group unique to women with gynecologic cancers that meets monthly. Our goal was to investigate perceived benefits of support group participation. Methods: We developed a prospective questionnaire to evaluate the CSRA Gynecologic Oncology Support Group (CGOSG) participant’s perceived effects of attending the group on their side effects and disease status. The questionnaire was distributed to patients attending CGOSG meetings over a 4 month period. 47 surveys were collected for analysis; Wilcox rank sum test was used as appropriate. Results: The common cancers were 52% ovarian, 26% endometrial and 62% were currently on therapy. The 3 top reasons that patients attended CGOSG were physician driven (28%), to meet other women with the same diagnosis (26%) and to learn more about their cancer (22%). The top 3 expectations of patients were emotional support (28%), bonding/companionship (21%), and cancer education (14%). The top 3 concerning physical side effects from their cancer or therapy were fatigue (21%), memory loss (14%), and peripheral neuropathy (14%). Patients with more than 5 visits reported that CGOSG participation improved their most concerning physical side effect (fatigue) with a median score of 7.5 ± 4 out of 10. The top 3 concerning emotional side effects identified were fear of recurrence (26%), living with uncertainty (20%) and defining a new sense of normal (15%). Patients reported the CGOSG improved their most concerning emotional side effect (fear of recurrence) with a median score of 9 ± 2 out of 10. Patients with more than one visit, not on treatment reported a higher quality of life score (p = 0.001) and perceived a positive impact on cancer therapy (p = 0.02) compared to patients on treatment. Conclusions: This is a first of a kind attempt to understand the impact of a well-organized support group on women with gynecological cancers which indicates that these women struggle with fear of recurrence and uncertainty, but are able to find some solace.
Defining Central Line-Associated Blood Stream Infections Following Hematopoietic Cell Transplantation in Acute Myeloid Leukemia and Myelodysplastic Syndrome.
Authors: Joshua Lukenbill, Lisa Rybicki, Mikkael A. Sekeres, Megan DiGiorgio, Thomas Fraser, Alexander Copelan, Hien K. Duong, Brian T. Hill, Matt Kalaycio, Ronald Sobecks, Rabi Hanna, Brian J. Bolwell, Edward A. Copelan
Journal: Blood (2012)
Histological architectures of clear cell carcinoma and their correlation to clinicopathologic features.
Authors: Go Kimura, Hayato Takeda, Jun Akatsuka, Yuki Endo, Yukihiro Kondo
Journal: Journal of Clinical Oncology (2016)

576 Background: The aim of this study is to clarify the relationship between histological architectures (HA) and clinicopathological features (CF) in clear cell carcinoma (CCC). Methods: Between 1984 and 2014 nephrectomy or partial nephrectomy were performed in 723 renal cell carcinoma cases in our hospital. Among them 603 cases (83.4%) were CCC. We reviewed the pathological reports and found 556 CCC cases had description of HA. The relationship between HA and CF were investigated. Results: HA were as follows: small acinar (SA)/acinar (A) in 453 cases (81.5%), large acinar (LA)/solid (S) in 113 (20.3%), papillary (P) in 54 (9.7%), Cystic (C) in 121 (21.8%) and tubular in 53 (9.5%). By the Spearman rank correlation, significant correlation was observed between HA and tumor grades: SA/A (rho -0.408, p &lt; 0.0001), LA/S (0.567, p &lt; 0.0001), P (0.257, p &lt; 0.0001), C (-0.241, p &lt; 0.0001). Acinar sizes were correlated with tumor grade (0.541, p &lt; 0.0001), tumor size (0.435, p &lt; 0.0001) and local stage (0.414, p &lt; 0.0001). LA/S or P showed low microvessel density evaluated by CD31 immunostaining, which resulted in weaker attenuation in corticomedullary phase of enhancement CT. On the contrary SA had high microvessel density and high attenuation after enhancement. Conclusions: HA is well-correlated with tumor grade, tumor size and local stage, and could be predicted by dynamic CT pattern preoperatively.
Immunohistochemical-based diagnosis of lung adenocarcinoma subtypes reproduces the results of gene expression profiling.
Authors: A. S. Lucas, M. D. Wilkerson, P. J. Roberts, M. C. Hayward, J. E. Grilley-Olson, T. Stinchcombe, M. A. Socinski, N. K. Veeramachaneni, B. E. Haithcock, W. K. Funkhouser, D. N. Hayes
Journal: Journal of Clinical Oncology (2011)

e21079 Background: The clinical classification of lung cancer relies almost exclusively on anatomic staging and histology. Molecular classification of lung adenocarcinoma has been proposed with prognostic significance and actionable phenotypes but is difficult to implement due to reliance on frozen tissue and gene expression arrays not in clinical use. Hypothesis: Lung adenocarcinoma can be subclassified into validated molecular subtypes using immunohistochemistry (IHC). Methods: Gene expression studies were reviewed to generate targets that reliably distinguish 3 validated molecular subtypes of lung adenocarcinoma (squamoid, magnoid, and bronchioid). The genes were crossed against approximately 200 clinically used antibodies; 3 were selected: thyroid transcription factor 1 (TTF1), smooth muscle actin (SMA), and vimentin (VIM). 190 human lung adenocarcinoma samples (30 pairs of tumor matched with tissue from recurrence, 75 paired frozen and paraffin embedded samples) were independently assessed for adenocarcinoma subtype using gene expression array and IHC. Mutation analysis was performed for EGFR and KRAS. Results: Gene expression array of lung adenocarcinomas revealed a pattern of 3 molecular subtypes (bronchioid, squamoid, and magnoid). Improved survival in the bronchioid subtype independent of stage was observed (p<0.05). EGFR was significantly associated with the bronchioid subtype and KRAS with magnoid subtype (p<0.05). A pattern of IHC staining correlated strongly with the subtypes by gene expression arrays in paired samples suggesting that this strategy could substitute for molecular subtype as determined by gene expression arrays: bronchioid (TTF1 high, SMA low, VIM low), magnoid (TTF1 high, VIM high, SMA low), squamoid (TTF1 low, VIM low, SMA high). Primary-recurrent tumor pairs demonstrated strong agreement. Conclusions: We confirm previous reports of the clinical significance of lung adenocarcinoma molecular subtypes including prognosis and association with mutation status and propose a pattern of staining by routine IHC that could be a proxy for gene expression array analysis.
Assessing the treatment quality of elderly patients with stage III colon cancer in a large community oncology network: A Fox Chase Cancer Center Partners (FCCCP) quality initiative
Authors: M. A. O'Grady, E. Slater, P. F. Engstrom, E. Sigurdson, N. J. Meropol, A. Weinstein, E. Sein, P. Keeley, B. Miller, S. J. Cohen
Journal: Journal of Clinical Oncology (2008)

6576 Background: FCCCP performs an annual quality review of affiliated community practices based on NCCN guidelines. Given recent treatment advances in stage III colon cancer, we initiated a chart review in patients (pts) age ≥65 years to assess incorporation of these advances in elderly pts. Methods: Charts of 124 pts age ≥65 diagnosed with stage III colon cancer between 2003 and 2006 were reviewed and a relational database used for data capture and report generation. Based on NCCN guidelines, specific metrics were developed for colon cancer, gerontology, and activities of daily living (ADL) documentation, treatment, and surveillance. Documentation was reviewed via paper record in 13 sites and electronic medical record in 2. Results: Compliance with NCCN guidelines for documentation was: staging (98%), pathology report (91%), colonoscopy (75%; 58% reaching cecum), CEA (91%), CT abdomen/pelvis (93%), and chest imaging (100%). ADL were documented commonly (83%), but age and life expectancy in relation to adjuvant chemotherapy was discussed in only 49%. Nearly all patients (123/124) received adjuvant chemotherapy, although only 76 (61%) received oxaliplatin. The most common regimens were FOLFOX (54%), bolus 5-FU/LV (19%), and capecitabine (12%). Documented reasons for not giving oxaliplatin were comorbidity (68%) and age (19%). Pathologic features indicated 74% had ≥12 lymph nodes retrieved and 56% had radial margin status identified. Nearly all patients (115 =93%) received appropriate surveillance with H+P and CEA. Abdominal and pelvic surveillance CT was performed in 78% of patients. Conclusions: A quality review of community oncology practices has high value in assessing real time implementation of treatment advances. Although we generally noted high compliance for elderly patients with stage III colon cancer, 40% of patients did not receive oxaliplatin and documentation of life expectancy was infrequent. Further research should focus on targeted education efforts in these areas and assessment of their impact. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration NCCN NCCN, sanofi-aventis NCCN
Uptake of bevacizumab for the treatment of colon cancer.
Authors: A. I. Neugut, D. J. Becker, B. J. Insel, D. L. Hershman
Journal: Journal of Clinical Oncology (2011)

6107 Background: While bevacizumab (BEV) has been shown to improve mortality when added to first-line treatment of metastatic colon cancer, a randomized trial presented at ASCO 2009 reported no benefit from the addition of BEV in stage III colon cancer. We investigated the uptake of BEV for the treatment of both early stage and metastatic colon cancer in a population-based sample. Methods: We identified patients >65 yrs diagnosed with stage III colon cancer, 9/1/04-12/31/05, in the SEER-Medicare database who were treated within 6 months of diagnosis. We also identified patients >65 yrs diagnosed with stage IV or recurrent colon cancer, 1/1/05-12/31/05. We used multivariable logistic regression models and Generalized Estimating Equations to assess the relationship between patient/physician characteristics and receipt of BEV for the metastatic cohort. Results: Among 1884 patients with stage III colon cancer, 825 (43.8%) were treated with chemotherapy of whom 55 (6.7%) had claims for BEV. Among 1,119 patients with stage IV or recurrent colon cancer, 441 (39.4%) had claims for chemotherapy, and of these, 312 (70.7%) had claims for BEV. Among 859 (76.8%) patients with metastatic disease seen by an oncologist, we found that younger age (OR 5.31 95%CI 3.02-9.35), being married (OR 1.72 95% CI 1.17-2.52), and fewer comorbidities (OR 2.04 95% CI 1.19-3.52) were associated with receipt of both chemotherapy and BEV, when compared to patients who received no chemotherapy. Patients who had younger physicians (OR 3.31 95%CI 1.92-5.73), US trained physicians (OR 1.47 95% CI 1.03-2.12), and physicians who treated more patients in our sample (OR 1.69 95% CI 1.19-2.41) were also more likely to receive chemotherapy with BEV. Among metastatic patients who received chemotherapy, we found that having no comorbidities (OR 2.33 95% CI 1.41-3.85), a male physician (OR 1.88 95%CI 1.14-3.12) and a physician who treated more patients in our cohort (OR 1.61 95%CI 1.02-2.54) were all associated with the additional receipt of BEV compared to no BEV. Conclusions: For patients with metastatic colon cancer treated with chemotherapy, uptake of BEV was very rapid, and influenced by physician characteristics. Despite a lack of efficacy, patients were also receiving it off-label in the adjuvant setting.
Beyond IGRT: Daily real time planning (RTP)—Treatment of prostate cancer, clinical implementation, and technique.
Authors: James Robert Wong, Scott Andrew Merrick, Mona Karim, Yana P. Goldberg, Jeff Gao, Mei Li, Paula Wilson, Madeline Klingeman
Journal: Journal of Clinical Oncology (2013)

191 Background: Image guided radiation therapy (IGRT) corrects for the interfractional movements of the target/CTV. However, the anatomic changes of CTV, and movements of the adjacent organs, are not accounted for. By modifying an online adaptive radiation technique proposed by Li, we have clinically deployed a daily “real-time treatment planning” (RTP) technique for treatment of primary prostate cancers. The technique, rationale and experience of our first 60 RTP treatments are presented. To our knowledge, this is the first clinical implementation of daily treatment planning. Methods: The RTP process is as follows: a) daily CT images are acquired via an in-room diagnostic CT-on-Rails; b) while IGRT evaluation is performed, new target and tissue contours (prostate, rectum and bladder) are drawn, c) new IMRT plan is computed (RTP plan); d) IGRT plan is compared to the RTP plan; e) if RTP plan is dosimetric superior, it will be delivered after f) necessary QA process. This entire process takes less than 20 minutes (excluding IMRT delivery). 60 RTP’s were delivered (10 daily RTP/patient) in 6 consecutive patients. Results: Auto-contouring via auto-segmentation was inadequate when compared to manual anatomic re-contouring. The RTP plan is always superior to or equal to the original IGRT plan. In 20% of the cases, the CTV-DVH by RTP improved by &gt;10%. Slight changes in manual contouring variation can lead to significant change in volume variation. For example, with initial prostate volumes of 15, 20, 30, 40 and 50 cc, a 1 mm increase in contour variation results in an increase volume of 26%, 24%, 21%,19% and 17% respectively, and absolute volume increase of 3.9cc, 4.8cc, 6.2cc, 7.4cc and 8.6cc respectively. Rectal dose improved significantly with RTP when compared to IGRT. In one extreme case, the rectal dose improvement is shown (Table). Conclusions: Daily RTP is feasible for prostate cancer treatments and is superior to IGRT. RTP is especially necessary with extreme anatomic changes. [Table: see text]
First-line mTOR inhibition in metastatic renal cell carcinoma (mRCC): An updated analysis from the International mRCC Database Consortium (IMDC).
Authors: Lauren Christine Harshman, Nils Kroeger, Sun Young Rha, Frede Donskov, Lori Wood, Srinivas Kiran Tantravahi, Ulka N. Vaishampayan, Brian I. Rini, Jennifer J. Knox, Scott A. North, Mary J. MacKenzie, Takeshi Yuasa, Sandy Srinivas, Sumanta Kumar Pal, Daniel Yick Chin Heng, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2013)

e15518 Background: FDA approval of the mTOR inhibitors (mTORi) in mRCC was based on efficacy in poor risk patients (pts) in the first line setting for temsirolimus (T) and in VEGF inhibitor-refractory pts for everolimus (E). Little is known about T’s effectiveness in good and intermediate risk patients and E’s outcomes in the first line setting. Methods: We interrogated the IMDC for the outcomes of pts who received mTORi as first-line targeted therapy. Results: 127 pts received a first line mTORi; the majority received T (93 T, 34 E). The main reasons for T administration were poor risk (38%), non-clear cell histology (27%), and clinical trial (15%) whereas clinical trial (82%) and non-cc histology (6%) drove E use. Of the T and E pts, 58% and 32% were poor risk, respectively. Median age was 61 years and median KPS was 80%. 68% had prior nephrectomy (62% T vs. 82% E). Median progression-free survival (PFS) and overall survival (OS) are detailed below. In the 97 pts with response data, 5% and 53% for T and 8% and 58% for E achieved partial responses and stable disease, respectively. Progressive disease as best response occurred in 41% for T and 33% for E. Second line therapy was captured in 52 pts (41%), of whom 48 received VEGF inhibitors. Conclusions: Given the different populations in which they were administered, direct comparisons of the frontline efficacy of T vs. E cannot be made. The majority of T pts were poor risk, which their dismal PFS and OS reflect. The better outcomes in the E pts highlight that the majority were not poor risk and were healthy enough for clinical trials. While limited by small numbers, this data characterizes a real world experience of mTORi in the first line setting. [Table: see text]