tbuckley/cabot-search huggingface dataset:
Palliative treatment directives for bone metastases: A quality-directed approach to guiding institutional practice.
Authors: Lindsay Puckett, Lucille Lee, Petrina Zuvic, Isabella Bingchan Zhang, Louis Potters, Beatrice Bloom
Journal: Journal of Clinical Oncology (2016)

188 Background: The efficacy of single fraction (fx) radiation treatment (RT) has proven to have equipoise for palliation of bone metastases when compared to courses of 10 fx or more. Despite these data, there has been a slow adoption of this practice in the US and worldwide. Examination of our multicenter practice from 2004 - 2016 showed that single fx RT utilization has remained at 17% and hypofractionationed (HFX) courses (1 or 5 fx) have remained at 71% since 2009. We hypothesized that evidence-based, treatment-guiding directives could improve HFX utilization in this population. Methods: Institutionally, palliative bone metastasis treatments are routinely tracked by a Quality Assurance committee. In 2/2016, two consensus-driven and evidence-based clinical directives were created within our electronic health system for use with either simple or complicated bone metastasis, irrespective of primary histology. The simple and complex directives had default prescriptions of 8 Gy/1fx or 20 Gy/5fx, respectively. The directives were reviewed with physician staff to improve compliance; directives were allowed to be edited at the physician’s discretion if an alternative fx was indicated. The chi-square test was used for analysis. Results: From 1/2009-5/2016, there were 1,781 treatment courses of palliative external beam RT. Following implementation in 2/2016, the new clinical directives were used for 96% of cases and were modified in 12 cases (n = 72). Single fx use increased from 17% to 36% among palliative bone metastasis treatments (p ≤ 0.001) and HFX (1 or 5 fx) utilization increased from 71% to 92% compared to other fractionation schemes (10 fx or other) (p = 0.001). Conclusions: The institution-wide adoption of evidence-based, treatment directives proved to be a straightforward and successful intervention which allowed for rapid adoption and increased utilization of the standard of care. Our early data suggests that this may be a useful approach in the setting of reticence to new treatment paradigms. Further examination of evidence based directives is warranted to address issues of overtreatment in palliation and in standardizing oncologic care.
Long-term survival results of the patients who were enrolled to the feasibility study of laparoscopy-assisted distal gastrectomy for c-stage I gastric cancer.
Authors: Haruhiko Cho, Kenki Segami, Taiichi Kawabe, Shigeya Hayashi, Yousuke Makuuchi, Takanobu Yamada, Shinichi Hasegawa, Kazuhito Tsuchida, Hitoshi Murakami, Tatsuya Yoshida, Tsutomu Sato, Takashi Ogata, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2015)

166 Background: We introduced laparoscopy-assisted distal gastrectomy (LADG) as multi-institutional feasibility study, and already reported that the overall morbidity rate was 1.6% in the study (Gastric Cancer 2012). The aim of this study is to evaluate the long-term survival results of the patients who were enrolled to the study and finished 5-year follow-up. Methods: A total of 165 c-stage I gastric cancer patients who were registered from Kanagawa Cancer Center were included to the study. The Kaplan-Meier method was used to evaluate overall survival and recurrence-free survival. Results: Median follow-up period of the patients was 1901 days. The reconstruction methods were either B-I (n=150), R-Y (n=14), or B-II (n=1). The accuracy for preoperative diagnosis of stage I was 87.2% (144/165). Among 14 patients with p-stage II/III excluding T3N0/T1N2-3, eight patients received postoperative adjuvant chemotherapy. The recurrence rates by pathological stage were 0% (0/123) for stage IA, 4.7% (1/21) for stage IB, 6.2% (1/16) for stage II, and 60% (3/5) for stage III/IV, respectively. The organ of recurrence was mainly observed in liver (n=3), followed by bone, lymph node, peritoneum (n=1). The 5-year recurrence-free survival rates were 94.5% for all patients, 97.2%/92.3%/60% for pT1/pT2/pT3/4, 98.5%/82.4%/71.4%/66.7% for pN0/pN1/pN2/pN3, 97.9%/81.3%/40% for p-stage I/p-stage II/p-stage III/IV. Conclusions: LADG for c-stage I gastric cancer was feasible in long-term result, as well as in short-term outcome.
Analysis of preoperative CT and peroperative evaluation as predictors of involvement of hepatic pedicle LN in patients operated for CRLM.
Authors: J. Belghiti, C. Rau, B. Blanc, M. Ronot, S. Dokmak, D. Fuks, V. Paradis, V. Vilgrain, S. J. Faivre
Journal: Journal of Clinical Oncology (2011)

375 Background: Approximately 20% of patients who undergo resection for colorectal liver metastases (CLM) have additional metastases present in hepatic pedicle lymph nodes (HPLN). Although LN status is a major prognostic factor, routine LN dissection is controversial. We evaluated the accuracy of preoperative CT scans and peroperative surgical assessment to determine if these methods could help determining which patients are at high risk for nodal metastases and should undergo lymphadenectomy. Methods: Between 01-2008 and 06-2010, 76 consecutive patients who underwent liver resection and lymphadenectomy for CLM after neoadjuvant chemotherapy were enrolled in a prospective study. All patients had recent (&lt;1 month) preoperative CT to evaluate their liver metastases and the presence, location, size and radiologic characteristics of LN were assessed. Peroperatively, the size and consistency of LN were evaluated by the surgeon. Surgeons and radiologists independently assessed LN involvement. Results were compared to the definitive pathologic examination. Results: Among the 76 patients, 241 nodes were analyzed with a mean number of 3 (± 2) nodes removed per patient. Lymphadenectomy increased the surgical procedure by 20 minutes (12-25 min) and there was no specific morbidity or mortality related to LN clearance. Pathologic HPLN involvement was observed in 15 (20%) patients with a median number of 2 (1-6) metastatic nodes per patient. Peroperative assessment had a high negative predictive value (NPV) = 91% with a low positive predictive value (PPV) = 43%. CT scan assessment had also a NPV and PPV of 85% and 56%, respectively. When considering both peroperative and radiologic data, 27% of patients with pathologic LN involvement were not anticipated and 25% of patients who were node negative on pathologic examination had suspected LN involvement. Conclusions: A selective strategy limiting HPLN clearance to high risk patients relies on information from preoperative CT scans and eroperative surgical assessment. Given that both modalities cannot accurately predict nodal pathologic status, routine HPLN dissection should be performed in patients who undergo resection of CRLM. No significant financial relationships to disclose.
Demographic, medical, and behavioral factors associated with colorectal cancer screening and diagnostic colonoscopy in Israel.
Authors: Miriam Gofine, Ora Paltiel, Orly Manor, Arnon Cohen, Einat Elran, Liora Valinsky, Eran Matz, Dena Hirschfield Jaffe
Journal: Journal of Clinical Oncology (2015)

557 Background: Colorectal cancer (CRC) is the third leading cause of cancer death worldwide and second leading cause of cancer death in Israel. Israel's universal health care system funds CRC screening (CRCS) (fecal occult blood testing or colonoscopy) for all adults aged 50-74. CRCS adherence is influenced by numerous factors including patient characteristics. In addition to screening asymptomatic individuals, those with anemia may have undiagnosed CRC and require aggressive case finding. This study’s goals were: 1) To compare the socio-demographic, health status, and health behavior characteristics of the eligible Israeli population who underwent any versus no CRCS (2009-2012); 2) To examine the relationship between anemia severity and CRCS likelihood; 3) To determine whether anemia status predicts time-to-CRCS. Methods: National retrospective cohort study of Israeli adults aged 51-71 on 1.1.2009 using electronic medical records from all 4 Israeli HMOs (n=1,009,898) over a 4-year period. Results: Differences in CRCS adherence were observed by patient characteristics. For example, ever-smokers comprised 17.9% of the screened population and 24.9% of the non-screened population (p&lt;0.001). Increasing anemia severity was positively associated with any CRCS performance, especially colonoscopy. For example, severely anemic individuals (hemoglobin &lt;10 g/dL for men, &lt;8 g/dL for women) were significantly more likely to receive colonoscopy than those who were not anemic (OR = 3.23; 95% CI, 2.58-4.27). Anemia somewhat expedites CRCS. For example, 8.9% of those with anemia and 7.6% of those without anemia performed any CRCS within 30 days of hemoglobin level recording (p&lt;0.001). Conclusions: Full CRCS adherence is not yet optimized in Israel. Particular attention directed at those at-risk for CRCS non-adherence may decrease CRC mortality. Although lower hemoglobin somewhat expedites colonoscopy performance, few individuals with anemia actually undergo colonoscopy. Further analysis accounting for confounding and effect modification is crucial for a more complete understanding of these relationships.
Inhibition of Shedding of Low‐Density Lipoprotein Receptor–Related Protein 1 Reverses Cartilage Matrix Degradation in Osteoarthritis
Authors: Kazuhiro Yamamoto, Salvatore Santamaria, Kenneth A. Botkjaer, Jayesh Dudhia, Linda Troeberg, Yoshifumi Itoh, Gillian Murphy, Hideaki Nagase
Journal: Arthritis & Rheumatology (2017)

The aggrecanase ADAMTS-5 and the collagenase matrix metalloproteinase 13 (MMP-13) are constitutively secreted by chondrocytes in normal cartilage, but rapidly endocytosed via the cell surface endocytic receptor low-density lipoprotein receptor-related protein 1 (LRP-1) and subsequently degraded. This endocytic system is impaired in osteoarthritic (OA) cartilage due to increased ectodomain shedding of LRP-1. The aim of this study was to identify the LRP-1 sheddase(s) in human cartilage and to test whether inhibition of LRP-1 shedding prevents cartilage degradation in OA.Cell-associated LRP-1 and soluble LRP-1 (sLRP-1) released from human cartilage explants and chondrocytes were measured by Western blot analysis. LRP-1 sheddases were identified by proteinase inhibitor profiling and gene silencing with small interfering RNAs. Specific monoclonal antibodies were used to selectively inhibit the sheddases. Degradation of aggrecan and collagen in human OA cartilage was measured by Western blot analysis using an antibody against an aggrecan neoepitope and a hydroxyproline assay, respectively.Shedding of LRP-1 was increased in OA cartilage compared with normal tissue. Shed sLRP-1 bound to ADAMTS-5 and MMP-13 and prevented their endocytosis without interfering with their proteolytic activities. Two membrane-bound metalloproteinases, ADAM-17 and MMP-14, were identified as the LRP-1 sheddases in cartilage. Inhibition of their activities restored the endocytic capacity of chondrocytes and reduced degradation of aggrecan and collagen in OA cartilage.Shedding of LRP-1 is a key link to OA progression. Local inhibition of LRP-1 sheddase activities of ADAM-17 and MMP-14 is a unique way to reverse matrix degradation in OA cartilage and could be effective as a therapeutic approach.
Influence of type of antecedent disorder on outcome of therapy-related AML.
Authors: S. R. Mohan, P. Elson, M. E. Kalaycio, R. V. Tiu, A. S. Advani, E. A. Copelan, J. P. Maciejewski, M. A. Sekeres
Journal: Journal of Clinical Oncology (2011)

6628 Background: Therapy-related AML (tAML) is an increasingly recognized consequence of chemoradiotherapy among cancer survivors but the latency period from antecedent diagnosis to its development is variable and not well-defined. Metaphase cytogenetics (MC) at tAML diagnosis effect prognosis, but the influence of the type of antecedent disorder for which treatment was previously given is less clear. Methods: We assessed retrospectively whether the type of antecedent diagnosis requiring therapy that led to tAML was predictive of response and overall survival (OS) following development of tAML. Results: Of 64 tAML patients (pts) treated with 7+3 chemotherapy over a seven year period, 67% had prior chemo/radiotherapy for a solid tumor (ST), 27% for a hematologic malignancy (HM), and 6% for an autoimmune disorder (AI). At tAML diagnosis, 18 pts (28%) had unfavorable MC, 33 (52%) intermediate, and 12 (19%) favorable, by CALGB risk criteria. The median latency from chemo/radiotherapy exposure to tAML was 4.7 years (range .5 – 41.5) and was inversely correlated to pt age (younger pts had longer latency, even if <65 years, Spearman r=-.42, p=.002). In multivariable analysis age at primary diagnosis (p<.001) and prior mitotic inhibitor exposure (p=.03) were predictors of shorter latency. Median age was 60 years, and 41 pts (64%) achieved CR. Age >60 was the only significant factor predictive of poor response. 2-year OS was 28%, with an estimated median OS of 11.7 months. Unfavorable MC (p=.01, hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.14-2.73) and an antecedent HM or AI (p=.04, HR 1.92, 95% CI 1.02-3.58) were independent predictors of inferior OS. There was a trend for worse OS among pts developing tAML 3-10 years following exposure, compared to tAML <3 or >10 years. Pts with unfavorable MC or with intermediate MC and tAML arising from HM or AI had significantly worse median OS than pts with favorable MC or with intermediate MC and tAML arising from ST (8.1 vs 20.8 months, p=.01, HR 2.24, 95%CI 1.21-4.15). Conclusions: The type of antecedent disorder for which pts receive therapy prior to development of tAML is relevant prognostically. Compared to pts treated for prior ST, pts treated for prior HM or AI exhibit worse OS to induction chemotherapy for tAML.
Patients’ general contentment with and quality of life (QoL) after treatment for prostate cancer (PC)
Authors: W. Wagner, J. Hartlapp, C. Hambrugge, U. Sanne, A. Radmard, L. Postawka, G. J. Wiedemann
Journal: Journal of Clinical Oncology (2008)

16052 Background: Cancer treatment has both beneficial and harmful effects. Benefits include prolonged survival and relief of cancer symptoms, potential harms are side effects and inconvenience associated with treatment. To assess the overall impact of treatment on QoL we evaluated the data of long term prostate cancer survivors after treatment. Methods: In October 2006, we published a QoL questionnaire in a patient cancer journal (Krebsmagazin) as well as on the corresponding website www.krebsmagazin.de. 634 patients (high aged: 86% 60–80 years old) had answered the 34 questions by March, 2007. This is the most extensive patient questionnaire evaluated in Germany concerning patients with PC. Results: Concerning late side effects and convenience of treatment, 96 % of all patients who underwent percutaneous irradiation (PI) were satisfied or very satisfied with their choice and would choose the same therapy again. Corresponding numbers were 93% for brachytherapy (BT), 84% for hormonal therapy (HT) and 79% for surgery. There was no difference between 3-D conformal irradiation (3DCR) and intensity modulated radiation therapy (IMRT). 32% of all patients irradiated percutanously suffered from erectile dysfunction and were unable to perform sexual intercourse (HT 63%, surgery 52%, BT 21%). 22% of patients irradiated percutaneously reported no sexual problems at all (21% BT, 13% HT, 4% surgery). With regard to psychological and physical deficits (fear, depression, urinary-/ bowel-/ erectile dysfunction, hormonal disorders), percutaneous irradiation is superior to the other treatment options. 49% of the patients stated they had no deficits after PI (36% after BT, 17% after HT, 15% after surgery). Conclusions: Regarding QoL and convenience, radiotherapy is superior to hormonal therapy and surgery in the treatment of patients with prostate cancer. There is no difference between 3DCR and IMRT. No significant financial relationships to disclose.
Retrospective analysis of systemic chemotherapy for unresectable advanced biliary tract cancer
Authors: H. Ishii, J. Furuse, T. Okusaka, K. Yamao, A. Funakoshi, S. Ohkawa, N. Boku, K. Tanaka, M. Nagase, H. Saisho, T. Sato
Journal: Journal of Clinical Oncology (2005)

4159 Background: Standard chemotherapy for biliary tract cancer (BTC) has not yet established. This study retrospectively examined the results of non-surgical treatments in patients with advanced BTC in order to clarify the relationship between treatment methods and prognosis following chemotherapy using historical controls. Methods: All patients receiving non-surgical treatments between April 2000 and March 2003 were examined in a multi-center review. The treatment methods, results and prognoses were analyzed. Survival from the start of the treatment was calculated by the Kaplan-Meier method. Results: Four hundred-twenty nine patients were recorded; 129 intrahepatic cholangiocarcinomas, 102 extrahepatic cholangiocarcinomas, 177 gall bladder cancers (GBC), and 22 ampulary papilla of Vater cancers. Systemic chemotherapy was administered to 211 (49.2%) patients, best supportive care to 143 (33.3%), radiotherapy or chemoradiotherapy to 62 (14.4%), hepatic arterial infusion chemotherapy to 11 (2.6%), and treatment was unknown in 2 (0.5%). Systemic chemotherapy regimens consisted of gemcitabine alone in 66 patients, CDDP-based in 47, 5FU-based in 34, FAM in 30, S-1 in 22, and other agents in 12. The overall response rate was 9.5% (20 partial responses), while the response rates of S-1 and FAM were both over 15%; S-1 was 18% and FAM 17%. The overall median survival time was 8.1 months, and the 1-year survival rate was 29.3%. There was no significant difference in survival among the regimens. Prognosis of GBC patients was significantly poorer than those with other BTCs. Conclusions: The response to chemotherapy and the prognosis of unresectable BTC patients were comparable to those of locally advanced or metastatic pancreatic cancer patients. A multi-center clinical trial is now on planning to optimize the use of BTC cancer resources in Japan. No significant financial relationships to disclose.
Prognostic impact of tumor-associated B-cells and plasma cells in esophageal and gastric adenocarcinoma.
Authors: Richard Fristedt, Charlotta Hedner, David Borg, Bjorn Nodin, Jakob Eberhard, Patrick Micke, Karin Jirstrom
Journal: Journal of Clinical Oncology (2016)

63 Background: Tumor immune cell infiltration has been shown to influence the prognosis and treatment prediction in several types of cancer and the focus has largely been on the innate immune system as well as the cell-mediated immune response. There are, however, recent findings suggesting an important role for the humoral immune system in stemming cancer progression. The aim of this study was therefore to investigate the prognostic impact of B cell and plasma cell infiltration in esophageal and gastric cancer. Methods: Immunohistochemical expression of the pan B-cell marker CD20 and plasma cell markers CD138 and immunoglobulin kappa C (IGKC), were analyzed in tissue microarrays (TMA) from primary tumors in a cohort of 174 consecutive, surgically treated cases of gastro-esophageal adenocarcinoma. A multiplier of intensity and fraction was calculated, and the median value was used for prognostic cut-off. Kaplan-Meier analysis, univariable and multivariable Cox regression analysis, adjusted for age, TNM-stage, resection margins and adjuvant chemotherapy, were used to determine the impact of IGKC, CD20 and CD138 expression on overall survival (OS). Results: A high density of IGKC+ plasma cells was significantly associated with a prolonged survival in esophageal (HR 0.41, 95% CI 0.21-0.78) and gastric adenocarcinoma (HR 0.50, 95% CI 0.28-0.88). A high density of CD138+ plasma cells was also significantly associated with prolonged survival but only in gastric adenocarcinoma (univariable HR 0.48, 95% CI 0.27-0.86, multivariable HR 0.51; 95% CI 0.27-0.97)). IGKC+ plasma cell expression remained significant in multivariable analysis, for esophageal (HR 0.50, 95% CI 0.26-0.97) and gastric adenocarcinoma (HR 0.50, 95% CI 0.27-0.94). There was no significant association between the density of CD20+ cells and survival. Conclusions: Our findings show, for the first time, that a higher density of stromal plasma cells correlates with a prolonged survival in both esophageal and gastric adenocarcinoma. These are new and encouraging findings that warrant further evaluation in additional patient cohorts.
Hormone Receptors, HER2/neu and p53 in 1027 Mexican patients with breast cancer
Authors: B. Crabtree, Y. Neme, S. Rivera, G. Olivares
Journal: Journal of Clinical Oncology (2005)

903 Background: In Mexico there are no significant epidemiologic studies concerning the hormonal receptors (HR), HER2/neu and p53 in breast cancer (BC). The purpose of this work was to study the frequency of each of these markers, the relationship between them and according to age groups. Methods: Data was obtained from the immunohistochemical (IH) area of the Pathology Department register of BC patients at the ABC Hospital for a 3 year period (2000–2002). Determination of HR, HER2/neu and p53 was performed by IH (positive estrogen receptor ER+ > 5%, positive progesterone receptor PrR+ >10%); HER2/neu overexpression was defined as positive immunomarking of 3+, (Herceptest). The frequency of each in the general population, and in the premenopausal (PrM) and postmenopausal (PoM) groups (defined as =< 50 years old and >50 years old, respectively) was analyzed. Results: IH reports of 1027 patients with BC were studied. The median age was 52.9. ER+ were found in 627 patients (61%) and PrR in 59% (n=610). The frequency HR+ (either ER+ and/or PrR +) was 68.9%. HER2/neu was measured in 966 of 1027 patients, being 3+ in 246 patients (25.5%). p53 gene mutation was determined in 915 patients, being positive in 670 (73.2%). We obtained 494 PrM patients, with a 66.6% HR+, and 71% in the PoM (n= 533), which was not statistically significant (p=0.119). HER2/neu was determined in 468 PrM patients, being 3+ in 114 (24.4%) versus 132/498 cases (26.5%) in the PoM group. p53 mutation was studied in 915/1027 patients, being positive in 670 (73.2%), 73.3% in PrM and 73.2% in PoM (p=0.95). Regarding the association among molecular markers, HER2/neu 3+ was found in 21.8% (n=150) of HR+ patients, while in HR- patients it was found in 30% (n=96), (p=0.44). Analyzed by age groups, the frequency of HER2/neu 3+ in PrM patients HR- was 22.3% versus 28.5% in the PoM group (p=0.005). Conclusions: According to these results, it can be noted that the number of patients that should be treated with hormone therapy is high. If the determination of HR is performed only in PoM patients, then, a great deal of PrM patients are being undertreated. It was also seen, that at least two thirds of the patients with BC can benefit with a monoclonal treatment along with chemotherapy and/or hormone therapy if indicated. No significant financial relationships to disclose.