tbuckley/cabot-search huggingface dataset:
Surgical density and its effect on esophageal cancer (EC) and gastric (GC) mortality.
Authors: M. Y. Ho, J. S. Albarrak, W. Y. Cheung
Journal: Journal of Clinical Oncology (2011)

16 Background: Surgical resection plays an integral role in the multimodality treatment of patients with EC or GC. The distribution of thoracic and general surgeons at the county level varies widely across the US. The impact of the allocation of these surgeons on cancer outcomes is unclear. Our aims were to 1) examine the effect of surgeon density on EC or GC mortality, 2) compare the relative roles of thoracic and general surgeons on EC and GC outcomes and 3) determine other county characteristics associated with cancer mortality. Methods: Using county-level data from the Area Resources File, U.S. Census and National Cancer Institute, we constructed regression models to explore the effect of thoracic and general surgeon density on EC and GC mortality, respectively. Multivariate analyses controlled for incidence rate, county demographics (population aged 65+, proportion eligible for Medicare, education attainment, metropolitan vs. rural), socioeconomic factors (median household income) and healthcare resources (number of general practitioners, number of hospital beds). Results: In total, 332 and 402 counties were identified for EC and GC, respectively: mean EC/GC incidence = 5.29/6.83; mean EC/GC mortality=4.70/3.92; 91% were metropolitan and 9% were rural; mean thoracic and general surgeon densities were 10 and 63 per 100,000 people, respectively. When compared to counties with no thoracic surgeons, those with at least 1 thoracic surgeon had reduced EC mortality (beta coefficient -0.031). For GC, counties with 1 or more general surgeons also had decreased number of deaths (beta coefficient -0.095) when compared with those without any surgeons. While increasing the density of surgeons beyond 10 only yielded minimal improvements in EC mortality, it resulted in significant further reductions in GC mortality. Other county characteristics, such as increased number of hospital beds and higher median household income, were correlated with improved outcomes. Conclusions: Mortality from GC appears to be more susceptible to the benefits of increased surgeon density. For EC, a strategic policy of allocating health resources and distributing the workforce across counties will be best able to optimize outcomes at the population-level. No significant financial relationships to disclose.
Paclitaxel-associated acute pain syndrome (P-APS) and its association on the development of peripheral neuropathy: NCCTG trial N08C1.
Authors: B. Reeves, S. R. Dakhil, J. A. Sloan, K. N. Burger, N. A. Le-Lindqwister, G. S. Soori, A. J. Jaslowski, J. Kelaghan, D. H. Lachance, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2011)

9047 Background: Paclitaxel is well known to cause an acute pain syndrome that has been referred to as arthralgias and myalgias. It has been hypothesized that this pain might actually be neurologic in origin (Loprinzi et al; Cancer J 2007; 13:399-403). A recent prospective cohort study evaluating the natural history of this paclitaxel-associated acute pain syndrome supported an association (p=0.0017) between the degree of paclitaxel-associated acute pain severity and the subsequent development of peripheral sensory neuropathy (Loprinzi et al; JCO, in press). Methods: Adult patients receiving at least 175 mg/m2 of paclitaxel every three weeks, with concomitant carboplatin, participated in this study. Patients completed questionnaires for 7 days following each dose of paclitaxel. They were asked to judge, on each day, pain that was new and that they thought was related to chemotherapy (graded on a scale of 0 to 10 with 10 being worst). They also completed questionnaires (EORTC CIPN-20 instrument) to collect neuropathy data at the beginning of each weekly cycle of therapy and monthly after chemotherapy completion. Descriptive statistics were utilized for study endpoints. Results: Eighty-five patients were accrued. Eighty-eight percent experienced pain, most prominent in the hips and lower extremities, which peaked at day 4 after the first paclitaxel cycle. Subjects who experienced less acute pain (scores of 0-4) with the first paclitaxel cycle had less neuropathy over 18 weeks of treatment than did patients with 5-10 pain score severities (Table). Conclusions: The paclitaxel-associated acute pain syndrome is common and does appear to be associated with the development of peripheral neuropathy. EORTC CIPN-20 endpoint Mean decrease in CIPN severity for P-APS score 0-4 (versus 5-10)* P value** Autonomic subscale 7.8 0.007 Motor subscale 7.9 0.004 Sensory subscale 11.3 0.001 Numbness—feet 17.0 0.001 Burning/shooting pain—feet 11.5 0.02 Tingling—feet 13.7 0.02 Numbness—hands 16.0 0.002 Burning/shooting pain—hands 8.7 0.02 Tingling—hands 11.0 0.04 * On a 0-100 point scale. ** Mixed modeling p values adjusted for age and race.
Concordance of preoperative US-guided tattooing of axillary lymph nodes to sentinel lymph nodes and comparison of their pathologic results according to imaging modalities in breast cancer patients.
Authors: Hye Jung Kim, Jin Hyang Jung, Ho Yong Park, Ji-young Park
Journal: Journal of Clinical Oncology (2015)

28 Background: We wanted to know the concordance of preoperative ultrasound (US)-guided tattooing of axillary lymph nodes (ALNs) to sentinel lymph node and to correlate MR and PET-CT findings with the final histologic results. Methods: Axillary US examination was performed for all breast cancer patients before sentinel lymph node biopsy. The detected lymph nodes in US were classified as negative (group I, enlarged but image-benign) or positive (group II, image-suspicious) finding for metastases based on US, MRI and PET-CT findings. US-guided tattooing for ALNs was performed preoperatively by injection of 3cc of activated charcoal into the cortex of lymph node and the adjacent soft tissue. We evaluated their concordance to sentinel lymph node and correlated the histologic results of US tattooed LN according to each imaging modality. Results: Forty ALNs were tattooed and sentinel nodes corresponded to tattooed nodes in all except one patient with a tattooed non-sentinel node. Ten in group I and 30 in group II on US, 18 in group I and 22 in group II on MR, and 19 in group I and 21 in group II on PET-CT. Eight cases had evidence of metastases in final histology, 2 (20.0%) in group I and 6 (20.0%) in group II on US, 4 (22.2%) in group I and 4 (18.1%) in group II on MR, and 6 (31.6%) in group I and 2 ( 9.5%) in group II on PET-CT. Conclusions: US-guided tattooing is a feasible method for marking ALNs. In addition, tattooed lymph nodes correlate well with sentinel nodes, which may obviate the need for additional localization for axillary staging.
Everolimus (EVE) versus temsirolimus (TEM) after first-line treatment with VEGF TKI in patients with metastatic renal cell carcinoma.
Authors: Shiven B. Patel, Neeraj Agarwal, JoAnn Hsu, Srinivas Kiran Tantravahi, David Gill, Winston Vuong, Julia A. Batten, David D. Stenehjem, Sumanta Kumar Pal
Journal: Journal of Clinical Oncology (2015)

460 Background: Given the lack of affordability with an oral drug like EVE and/or preference in some patients (pts), TEM has been used after disease progression on a vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). However, efficacy of TEM and EVE in this setting has not been evaluated in a randomized trial. Methods: Pts who were treated with a first VEGF TKI for metastatic renal cell carcinoma (mRCC) and then treated with either EVE or TEM upon progression were identified from two institutional databases. Survival estimates of progression free (PFS) and overall survival (OS) were assessed from initiation of second-line (2 nd ) treatment by Kaplan-Meier methodology. Results: 90 pts were eligible that received either EVE (n=59; 66%) or TEM (n=31; 34%) in 2 nd setting. Pts and disease characteristics were similar in both groups. Median PFS was not different, but OS was significantly improved with EVE (Table). Conclusions: After progression on a 1 st VEGFTKI, 2 nd EVE and TEM have similar efficacy in terms of PFS, but OS was significantly higher with EVE. Data need further validation in a larger cohort. [Table: see text]
Barriers to clinical trial accrual in a community cancer clinic.
Authors: Cheruppolil R. Santhosh-Kumar
Journal: Journal of Clinical Oncology (2014)

91 Background: The availability of and enrollment in clinical trials at an institution may be considered cancer care quality measures. Nationally, most cancer patients are initially diagnosed and treated in the community setting. Data regarding clinical trial accrual of new cancer patients from community-based cancer centers and the barriers they encounter are limited. We sought to identify potential barriers to enrollment in clinical trials at a community cancer clinic. Methods: Data on new cancer patients seen at our comprehensive community cancer clinic were prospectively collected from 2007 through 2010. Factors that potentially affected patient accrual in clinical studies were tracked. Results: During the four-year study period, a total of 662 patients were diagnosed with breast, prostate, colon, lung, gynecological, melanoma and renal cell cancers. No studies were available for 42% of the patients (n=278). Of the remaining patients, 49% (190/384) met protocol eligibility. Of the eligible study patients, 45% (85/190) enrolled, for an overall accrual rate of 13% (85/662), and 55% (105/190) declined participation. Patients declined to participate due to stress of diagnosis, refusal of treatment entirely, issues with randomization and placebo, concerns with side effects of the medications, delay of treatment while awaiting the clinical trial process, patient refusal, transportation concerns and length of treatment. Conclusions: This study demonstrates that above average clinical trial participation can be achieved in community cancer clinics in the rural setting. There are modifiable barriers to clinical trial accrual including study availability, patient eligibility and other patient factors. Improvement of patients’ perceptions and perspectives regarding the clinical trial process could be achieved through patient education. Elimination of barriers to trial accrual could be studied as a quality metric.
Decitabine for the treatment of acute myeloid leukemia (AML): Memorial Sloan-Kettering Cancer Center experience.
Authors: A. Ganetsky, N. G. Adel, M. G. Frattini, P. G. Maslak, M. L. Heaney, J. G. Jurcic, M. S. Tallman
Journal: Journal of Clinical Oncology (2011)

6593 Background: Decitabine is a cytosine nucleoside analog that is FDA-approved for previously untreated and treated patients with myelodysplastic syndromes. Recent studies have also demonstrated clinical activity of decitabine in AML as it has been investigated for remission induction (Cashen et al J Clin Oncol, 2010; Blum et al PNAS, 2010), salvage therapy and bridging to hematopoietic cell transplantation (HCT). We conducted a retrospective analysis of the efficacy of decitabine in patients with AML treated at Memorial Sloan-Kettering Cancer Center (MSKCC). Methods: Using the pharmacy database, patients who received decitabine for AML between June 2006 and August 2010 at MSKCC were identified. Patients had to be at least 18 years of age treated for AML with single-agent decitabine at 20 mg/m2 daily for 5 days to be included. The primary endpoint was the rate of complete remission (CR). Secondary endpoints include time to response and median overall survival. Results: Sixty patients with a mean age 61.9 (range 28-80) were treated at MSKCC between the specified time period. Thirteen (22%) patients received decitabine as initial remission induction therapy. Of the 47 (78%) patients that received decitabine as salvage therapy, 14 were post HCT. The average number of prior salvage chemotherapy regimens was 2.5. Decitabine was successfully used as bridge therapy to HCT in 3 patients. The overall response rate was 13% as 7 (12%) patients achieved a CR and 1 patient achieved PR. The mean number of cycles to achieve maximal response was 3.25 cycles. Three of 13 (23%) patients that received decitabine as initial remission induction therapy achieved a CR. Only 4 (8.5%) patients receiving decitabine as salvage therapy achieved a CR. Conclusions: Our results support earlier reports of the promising role of decitabine in the treatment of patients with newly diagnosed AML who are not candidates for intensive chemotherapy. However, the use of decitabine as a salvage regimen needs to be re-evaluated as our results demonstrated a rather poor response rate. Future studies are warranted to better understand the clinical benefit of decitabine in AML, particularly the efficacy of the 10-day regimen and bridge therapy to HCT.
Differential efficacy of pemetrexed in nonsquamous NSCLC based on human cytokeratin fragment antigen 21-1 (CYFRA21-1) serum levels.
Authors: K. Kaburaki, A. Horiike, T. Sakatani, R. Saito, H. Tanaka, N. Yanagitani, K. Kudo, F. Ohyanagi, S. Hagiwara, T. Horai, M. Nishio
Journal: Journal of Clinical Oncology (2011)

10612 Background: Recent clinical trials demonstrate that histology is an important factor in NSCLC for individualized treatments based on safety or efficacy outcomes. However, several problems persist with histology-based treatments. The main problem is that it is difficult to obtain adequate biopsy specimens to accurately distinguish the histological subtypes of NSCLC. Therefore, a more objective, yet simple biomarker for histology-based treatment is needed. Human cytokeratin fragment antigen 21-1 (CYFRA21-1) is one of the tumor markers for NSCLC and may be representative of the squamous subtype. In this study, we examined whether serum CYFRA21-1 levels were associated with the efficacy of pemetrexed in NSCLC. Methods: From September 2009 to December 2010, 46 previously treated NSCLC patients who received pemetrexed monotherapy (500 mg/m2 every 3 weeks) until disease progression were evaluated. Serum concentrations of CYFRA21-1, CEA, SCC, and sialyl Lewis X-i antigen (SLX) were measured. We analyzed possible associations between these NSCLC marker levels and pemetrexed treatment efficacy. Results: Patient characteristics were: male/female = 22/24; median age = 63 yrs. (34-79 yrs.); histology: adeno/large/NOS = 42/2/2; PS: 0/1/2/3= 25/19/1/1. For these 46 patients, elevated levels of serum CYFRA21-1, CEA, SCC, and SLX were found in 18, 30, 12, and 33 patients, respectively. PFS for patients with elevated serum CYFRA21-1 was significantly shorter than for patients without elevated serum CYFRA21-1 (median PFS: 81 vs. 111 days; P=0.035), whereas no significant differences in PFS were observed for CEA, SCC, or SLX levels. Conclusions: Serum CYFRA21-1 levels are associated with the efficacy of pemetrexed in NSCLC and may be a predictive marker for pemetrexed use. We are planning a larger scale study to confirm this observation.
Influence of one-year androgen deprivation therapy on lipid and glucose metabolism in patients with newly diagnosed prostate cancer.
Authors: Koji Mitsuzuka, Atsushi Kyan, Kazuhiko Orikasa, Yasuo Fukushi, Hiroshi Aoki, Shintaro Narita, Takuya Koie, Minoru Miyazato, Narihiko Kakoi, Yoichi Arai
Journal: Journal of Clinical Oncology (2014)

87 Background: The adverse events of androgen deprivation therapy (ADT) are widely recognized, but ADT-induced alterations in lipid and glucose metabolism may be race-dependent. We prospectively recruited Japanese patients with newly diagnosed prostate cancer who underwent at least one year of ADT and examined changes in lipid and glucose metabolism in these patients. Methods: Patients with newly diagnosed prostate cancer were recruited between January 2011 and August 2012. Body weight, abdominal circumference, and blood testing results were recorded every three months, and visceral and subcutaneous fat were measured by computed tomography before and after one year of ADT. Results: One hundred three patients completed a one year course of ADT. Median age was 74 (range, 50 to 85). Thirty nine patients underwent ADT with luteinizing hormone-releasing hormone (LHRH) agonist monotherapy, while 64 patients underwent ADT with LH-RH agonist plus bicalutamide. Median prostate-specific antigen (PSA) before ADT was 16.7 ng/ml (range, 3.6-3316 ng/ml). Clinical stage was B (46.6%), C (28.2%), and D (25.2%). Mean increase in body weight, abdominal circumference and body mass index after one year of ADT was 3.8%, 4.1%, and 3.8%, respectively. Mean decrease of hemoglobin was 5.5%. Mean increase of total, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides was 9.0%, 10.8%, 5.0%, and 21.0%, respectively. Mean increase in fasting blood sugar and HbA1c was 4.6% and 1.7%, respectively. Changes in each variable from baseline to 0, 3, 6, 9, and 12 months was as follows: body weight, 0, 0.9, 2.7, 3.3, and 3.8%; hemoglobin, 0, 4.5, 3.7, 5.5, and 5.5%; total cholesterol, 0, 12.9, 11.4, 9.7, and 9.0%; triglycerides, 18, 26, 25, 21%; and HbA1c, 0, 2.1, 1.2, 1.2, and 1.7%. Increase of visceral and subcutaneous fat measured by computed tomography before and after one year of ADT was 32.4% and 35.4%, respectively. Conclusions: One year of ADT caused significant changes, especially in lipid metabolism, in Japanese patients with prostate cancer. Visceral and subcutaneous fat increased more than 30%. These changes were noticeable in the first half of the one year course of ADT. Appropriate monitoring and management of these patients is needed, because these changes might cause critical cardiovascular events. Clinical trial information: UMIN000004709.
Salvage therapy with high-dose chemotherapy (HDCT) and peripheral blood stem cell transplant (PBSCT) in patients with primary mediastinal nonseminomatous germ cell tumors (PMNSGCT).
Authors: F. C. Asirwa, L. H. Einhorn
Journal: Journal of Clinical Oncology (2011)

e15119 Background: Salvage therapy with high dose chemotherapy (HDCT) and bone marrow transplant (BMT) or peripheral blood stem cell transplant (PBSCT) has curative potential in patients with recurrent germ cell tumor. Patients with primary mediastinal non-seminomatous germ cell tumors (PMNSGCT) have had poor results with any form of salvage chemotherapy including HDCT. From 1986 to 1996, we included 13 patients with PMNSGCT in our series treated with HDCT and BMT. All died from progressive cancer. Methods: We switched from BMT to PBSCT in 1996, allowing more rapid engraftment and earlier initiation of the second course of HDCT with tandem transplant. 116 of 184 (63%) patients with recurrent or refractory germ cell tumors treated from 1996 to 2004 were alive and continuously disease free (NEJM 357:340-348, 2007). PMNSGCT patients were excluded. In 2006, we resumed treating patients with recurrent PMNSGCT with salvage HDCT with PBSCT. Carboplatin 700mg/m2 x 3 plus etoposide 750mgs/m2 x3 were given with second course 3-4 weeks later. Results: 12 patients were treated, 11 as initial salvage chemotherapy and one as 4th line therapy. Eight patients had major thoracic resections prior to HDCT. 3 of the 12 achieved complete remission (52, 12 and 12 weeks duration) but all have relapsed. 10 of the 12 have died; one is lost to follow-up at 44 weeks, and one patient is currently disease free at 176 weeks from HDCT, treated with subsequent salvage surgery. However, he developed secondary acute myeloid leukemia and underwent allogeneic BMT. Median survival for the 12 patients was 41 weeks (range 14-176). Conclusions: In our experience with tandem transplant, recurrent PMNSGCT continues to have a low probability for cure.
Hepatitis B viral load to predict survival of HCC patients treated with sorafenib.
Authors: Seungtaek Lim, Kwang-Hyub Han, Hye Jin Choi
Journal: Journal of Clinical Oncology (2014)

188 Background: Sorafenib demonstrated survival prolongation in patients with advanced hepatocellular carcinoma (HCC). Until now, the effect of HBV DNA titer on prognosis of HCC patients treated with sorafenib has not been determined. Methods: From 2008 to 2012, 78 HBV-related HCC patients who received sorafenib at Severance hospital were included in our analysis. The prognostic effect of pretreatment HBV DNA level was examined by univariate and multivariate analysis. Results: The median overall survival was 5.2 months (95% confidence interval [CI]: 4.0-6.4) and median progression free survival was 3.5 months (95% CI: 2.3–4.7). Multivariate analysis revealed that a high baseline HBV DNA level (&gt;2,000 IU/L) was an independent risk factor for worse overall survival (p=0.005; hazard ratio [HR], 2.85), and rapid disease progression in a subgroup who did not receive antiviral prophylaxis with sorafenib (p=0.008; HR, 87.4). Moreover, viral reactivation occurred more frequently in patients who did not receive prophylactic antiviral therapy with sorafenib compared to those who did (4/38 vs. 0/40; p=0.025). Conclusions: A higher HBV DNA level before sorafenib was associated with poorer prognosis and increased viral reactivation. This result suggests the role of prophylactic antiviral therapy in patients who received sorafenib. [Table: see text]
The high incidence of vascular thromboembolic events (VTE) in advanced urothelial cancer (UC) patients (pts) treated with carboplatin (Cb): Analysis of treatment with gemcitabine (G)/cb (GCb), gcb/bevacizumab (GCbBev), or gemcitabine/cisplatin (GCis).
Authors: Christopher Michael Tully, Andrea Borghese Apolo, Emily C. Zabor, Ashley Marie Regazzi, Irina Ostrovnaya, Jonathan E. Rosenberg, Dean F. Bajorin
Journal: Journal of Clinical Oncology (2014)

316 Background: VTE occur in ~13% of pts receiving Cis-based therapy for UC. Cb-based therapy is considered less thrombogenic but no definitive data exist to support this conclusion. While Bev added to chemotherapy (Ch) increases VTE in other tumors, VTE impact when added to UC Ch is unknown. This study evaluated the incidence of and etiologic factors for VTE in UC pts treated with GCb, GCbBev and GCis. Methods: UC pts treated from 6/2006 to 6/2010 on a GCbBev protocol were analyzed prospectively. Planned therapy was 6 cycles of GCbBev then Bev alone; pts who had ≥ 3 cycles were included. Similar UC pts treated with GCb or GCis during the same time were retrospectively evaluated. Type of VTE and potential contributing clinical factors were collected. VTE was defined as pulmonary embolism, vascular thrombosis, myocardial infarction or cerebral vascular accident. Associations with Ch regimen were tested using Fisher’s exact test or linear regression. Factors associated with VTE were analyzed using conditional logistic regression stratified by Ch regimen. Results: 198 pts were analyzed. VTE occurred in 13/51 (26%) GCbBev pts, 22/92 (24%) GCb pts, and 8/55 (15%) GCis pts. Age (≤65 vs &gt;65; p&lt;0.001), having had a prior cystectomy (p&lt;0.001), mass near pelvic vessels (p=0.027), Khorana risk group (p=0.025) and anti-platelet therapy (p=0.036) were significantly associated with the Ch regimen reflecting cohort-specific differences. Type of Ch was not associated with any VTE (p=0.3) or type of VTE (arterial vs venous) (p=0.11). Having had a prior cystectomy was associated with increased risk of VTE (OR 2.2, 95% CI 1.0-5.0, p=0.047). Conclusions: This is the largest series reporting VTE in Cb-treated UC pts; the VTE rate of 24% (95% CI 17, 32%) is higher than expected. Bev does not appear to increase this risk. VTE in Cis-treated pts (15%) was similar to prior reports. The finding that pts with advanced UC are at high risk of VTE regardless of the specific platinum agent warrants further study of Cb therapy-related risk and analysis for contributing factors including prior pelvic surgery.