tbuckley/cabot-search huggingface dataset:
CNS metastases as a site of progression on SWOG intergroup study S0008: A phase III trial of high-dose interferon alpha-2b versus cisplatin, vinblastine, DTIC plus IL-2 (BCT) versus high-dose interferon (HDI) in patients with high-risk melanoma.
Authors: Wolfram E. Samlowski, James Moon, Merle Witter, Michael B. Atkins, John M. Kirkwood, Megan Othus, Antoni Ribas, Vernon K. Sondak, Lawrence E. Flaherty
Journal: Journal of Clinical Oncology (2012)

8527 Background: Central nervous system (CNS) metastases (mets) are common in stage IV melanoma patients (pts). However, the incidence of CNS mets in pts with high-risk regional melanoma (HRM; stages IIIA-N2a thru IIIC N3) is not well described. A recent large prospective S0008 trial provided an opportunity to evaluate the contribution of CNS mets to treatment failure and survival. Methods: All pts had HRM treated with wide excision and full regional lymphadenectomy. Pts were then randomized to receive treatment with either BCT or HDI. All eligible pts were included in the analysis. Relapse/progression in the CNS (PCNS) was retrospectively identified only if clearly documented in case report forms. The cumulative incidence of PCNS in the presence of the competing hazard of death was estimated and potential risk factors were explored using the methods of Fine and Gray. Survival from PCNS was measured from date of PCNS to date of death. Results: 402 patients were evaluated (BCT: 200, HDI: 202), with median follow (if alive) of 6 years. The site of progression was identified in 162 (78 %) of 208 pts relapsing on study. Clearly documented PCNS occurred in 53/402 pts (13%). PCNS as a component of initial relapse/progression occurred in 34 patients (8%) and an additional 19 patients (5%) had delayed PCNS following initial systemic relapse. Most PCNS (85%) occurred within 3 years of initial surgery. Differences between arms were not significant (22 on BCT, and 31 on HDI)(p=0.21). Lymph node macromets demonstrated a strong correlation with development of PCNS (p=0.01). Neither primary tumor ulceration nor head and neck primary site were significant risk factors. Survival from diagnosis of brain mets was short (median 6 mo BCS, 5 mo HDI, p=0.93). Conclusions: Although the S0008 trial was not specifically designed to evaluate PCNS, a retrospective analysis identified a high CNS failure rate (at least 13%) in HRM pts, including 8% as the initial site of relapse. Further studies are needed to evaluate if screening for CNS mets in high-risk pts is useful and whether early treatment improves survival.
Creating a risk of readmission (ROR) score for gynecologic oncology (GO) patient.
Authors: Kristy K. Ward, Nina R. Shah, Mitzie-Ann Davis, Cheryl C. Saenz, Michael T. McHale, Steven C. Plaxe
Journal: Journal of Clinical Oncology (2013)

6636 Background: The annual cost of 30 day hospital readmissions in the US is $16 billion. The objectives of this study are to determine factors associated with readmission among GO patients, and to create a risk score to identify populations at the highest risk of readmission. Methods: The University HealthSystem Consortium database was queried to identify readmissions among GO patients from 1/1/08 through 9/30/12. Risk factors for 30 day readmission were determined by univariate and multivariate analysis. For each risk factor found to be independently associated with readmission, the low risk group was scored 0 and the high risk group scored 1. The ROR score is the sum of the individual scores. Probability of readmission was calculated for each ROR score. Results: Overall, the readmission rate for GO patients was 4.5%. Vulvar cancer, medical MSDRG, urgent or emergent admission, length of stay &gt; 4 days, and coverage by a public payer (during 1st admission) each was independently associated with readmission. Probability of readmission increases significantly with increasing risk score. Patients with a ROR score of 0 or 1 have a readmission rate of 3.9% (95% CI 3.7% to 4.1%); patients with a ROR score of &gt;1 have a readmission rate of 10.7% (95% CI 10.1% to 11.2%). Conclusions: Specific risk factors and composite risk score are associated with 30 day readmission rate among GO patients. The patient specific ROR score may be used to target transitions of care interventions aimed at reducing readmissions. [Table: see text] [Table: see text]
The need for psychooncological support in breast cancer patients: A longitudinal study.
Authors: Ralf R. Reichelt, Christian M. Kurbacher, Roland Schnell
Journal: Journal of Clinical Oncology (2015)

e20565 Background: Breast cancer is frequently associated with psychooncological burden for the affected patients. However, the extent of this burden is often not readily assessable, as many patients do not express their need for professional counselling. The aim of this study was to identify breast cancer patients in need of psychooncological support and to monitor these patients in the long-term. Methods: To assess the patients’ burden, the standardized self-rating Questionnaire for Psycho-Oncological Burden of Cancer Patients, (10 items, FBK-R10) was to be answered by each patient (n = 82) at different time points during their treatment in either of two participating German oncological practices from 02/2012 – 10/2014. Results: According to the initial survey, a total of 37 patients (45.1%) needed psychooncological support. This need was still present in 62% of these patients, at the time of the second FBK-R10, which in the median was answered 29 months later. When considering solely adjuvant/curative treated patients (n = 27), the second FBK-R10 results indicated that 54% of the initially affected patients still needed psychooncological support. At the same point in time, a substantial higher proportion (73%) of initially burdened palliative patients (11 out of 22 patients) still required support. Conclusions: The psychooncological burden in breast cancer patients is influenced by many factors. In this context, the FBK-R10 has proven to be an appropriate instrument to identify these factors, and thus to reveal the need for psychooncological support. Early intervention and initiation of adequate measures as well as long-term monitoring is necessary to meet the individual requirements of breast cancer patients.
Surgical, radiological, and chemotherapy treatment patterns for non-metastatic and metastatic gastric cancer.
Authors: Kenneth Shermock, Brian S. Seal, Carl V Asche, Jane Chang, Fang Xia, Jonathan K Kish, Erin Zagadailov, Michael Eaddy
Journal: Journal of Clinical Oncology (2015)

e15010 Background: Describe the patterns of surgical, radiological, and chemotherapy treatments patterns among patients diagnosed with metastatic (M) and non-metastatic (NM) gastric cancer (GaCa). Methods: Two large integrated claims databases (Pharmetrics, MarketScan) were used to identify patients ≥ 18 years old diagnosed and treated for GaCa from July 2008-September 2012. Patients were required to be chemotherapy (chemo)-naïve and continuously enrolled for ≥ 6 months pre- and post-diagnosis and have no other cancer diagnosis at baseline. Eligible patients were stratified into cohorts based on the presence and timing of M diagnosis: ≤ 120 days (M1); ≥ 121 days (M2). Results: There were 5,609 (3,486 NM; 1,469 M1; 654 M2) and 3,203 (2,004 NM; 875 M1; 324 M2) patients in each of the databases meeting all inclusion criteria, respectively. Median follow-up time was 19.1–20.9 months. No treatment was observed in 28.4–31.7% of NM patients and 67.2–69.7% received surgery. Between 12.3–16.5% of NM patients received first-line chemo compared to 73.7–79.4% of M1 and 64.8–70.8% of M2 patients. 92.3–92.5% of M1 patients and 81.2–82.3% of M2 patients received surgery within 6 months of diagnosis. The most common treatment sequences of M1 and M2 patients included surgery/chemo (25.4–31.3% and 16.7–19.7%), surgery/radiation/chemo (22.4–23.0% and 28.1–30.3%), and surgery/chemo/radiation (19.2–20.4% and 13.3–16.1%). Conclusions: Treatment patterns between 2 databases were similar. Nearly one-third of NM patients were not treated during the follow-up period. For M patients, the majority received surgery followed by chemo or radiation. Thus, the majority of patients received perioperative therapy in line with recommendations.
Effect of green tea polyphenol on changes in cancer-related factors in a mouse model of bladder cancer.
Authors: Tomohiro Matsuo, Yasuyoshi Miyata, Yuichiro Nakamura, Yasuda Takuji, Akihiro Asai, Kojiro Ohba, Hideki Sakai
Journal: Journal of Clinical Oncology (2017)

329 Background: Many studies have demonstrated the anti-cancer effects of green tea polyphenol (GTP) in a variety of malignancies including bladder cancer, and epidemiologic studies have shown that green tea consumption reduces cancer risk. New cancer treatment strategies in combination with GTP intake have been recommended for several types of cancer. Thus, GTP is thought to be useful not only for cancer prevention but also for treatment. However, the mechanistic basis of these effects is not well understood. Hence, The aims of this study is to clarify the molecular mechanisms of GTP-induced anti-cancer effects, we used a mouse model of chemically induced bladder cancer. Methods: C3H/He mice (8 weeks old; n = 46) were treated with 0.05% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) solution for 14–24 weeks. Mice in the BBN + GTP group (n = 47) were also treated with 0.5% GTP solution over the same period. Tumor cell proliferation, and microvessel density were evaluated along with immunohistochemical analysis of human antigen R (HuR), vascular endothelial growth factor (VEGF)-A, cyclooxygenase (COX)-2, and hemeoxygenase (HO)-1 expression. Results: Cytoplasmic HuR expression in cancer cells was higher at 14 and 24 weeks in the BBN than in the control group and was associated with increased invasion of tumor cells in muscle. However, these effects were not observed in the BBN + GTP group. A multivariate analysis of GTP intake and cytoplasmic HuR expression revealed that GTP was independently associated with COX-2 and HO-1 expression, while cytoplasmic HuR expression was associated with COX-2 and VEGF-A levels. Expression of COX-2 and HO-1 was associated with cell proliferation and that of VEGF-A and HO-1 was associated with angiogenesis. In regard to nuclear HuR, its expression was not associated with any parameters, such as carcinogenesis, muscle invasion, and GTP intake. Conclusions: Our results supported the opinion that GTP intake can suppress tumor progression and malignant behavior in animal model of bladder cancer. In addition, we speculate that GTP directly and indirectly suppresses tumor cell proliferation and angiogenesis via HuR-related pathways in bladder cancer tissue.
Biomarker analysis of a randomized, placebo-controlled, double-blind, multicenter phase II trial of intravenous RO5137382/GC33 at 1600 mg Q2W in previously treated patients with unresectable advanced or metastatic hepatocellular carcinoma (HCC) (NCT01507168).
Authors: Oscar Puig, Ya-Chi Chen, Eliezer Shochat, Christine Rossin, Olga Rutman, Lori Jukofsky, Jasbinder Bajwa, Bernhard Reis, Chia-Huey Ooi, John Allard, Anton Belousov, Qin Su, Christian Gerdes, Laura Di Laurenzio, Mikiko Nakamura, Norihisa Ohishi, Takayoshi Tanaka, Toshihiko Ohtomo, Reuy-min Lee
Journal: Journal of Clinical Oncology (2014)

e15090 Background: Glypican-3 (GPC3) is an oncofetal protein frequently expressed in HCC. GC33 is a humanized monoclonal antibody against GPC3. Preclinical studies suggested that GC33 triggers antibody-dependent cytotoxicity (ADCC) against GPC3 expressed HCC. Methods: This is a double-blinded randomized placebo-controlled trial comparing placebo with GC33 with a primary endpoint of Progression Free Survival (PFS). 185 patients were assigned into three cohorts based on GPC3 IHC status: A (GPC3 2/3+), B (GPC3 1+) and C (GPC3 0). Tumor assessment was based on RECIST criteria. Biomarkers analyzed were: tumor and circulating GPC3, blood immune cell subtypes, functional marker expression of NK cells, blood ADCC activity, tumor CD16, FcγRIIIa polymorphism F158V and tumor gene expression. Results: CD16 (FcγRIIIa) protein expression in peripheral blood cells was identified as a potential predictive biomarker for GC33 efficacy, since patients with CD16 values above the median appear to benefit from GC33 treatment (median PFS improvement from 1.7 to 4.2 months). Blood ADCC activity and FcγRIIIa polymorphism support a role of CD16 in the mechanism of action of GC33 since patients with higher baseline ADCC activity, or carriers of the Val aminoacid at position 158 in FcγRIIIa, appear to benefit from GC33 treatment (median PFS improvement from 1.5 to 4.1 months). There was a weak correlation between GPC3 expression in tumor as measured by IHC and a soluble form of GPC3 secreted in circulation measured by ELISA assay, and subgroup analysis showed that tumor or circulating GPC3 levels have no predictive value as biomarkers of response to GC33 treatment. Conclusions: GC33 efficacy seems to be promoted by a higher ADCC basal activity, higher expression of CD16 at the surface of blood cells or Val polymorphism in FcγRIIIa gene. GPC3 expression levels, or signaling downstream GPC3, are not informative as a marker of response. Further studies are needed to investigate whether patients with a specific immune environment may benefit from GC33. Clinical trial information: NCT01507168.
Screening for Excessive Alcohol Use and Brief Counseling of Adults — 17 States and the District of Columbia, 2014
Authors: Lela R. McKnight-Eily, Catherine A. Okoro, Roberto Mejia, Clark H. Denny, John Higgins-Biddle, Dan Hungerford, Dafna Kanny, Joseph E Sniezek
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Excessive and/or risky alcohol use* resulted in $249 billion in economic costs in 2010 (1) and >88,000 deaths in the United States every year from 2006 to 2010 (2). It is associated with birth defects and disabilities (e.g., fetal alcohol spectrum disorders [FASDs]), increases in chronic diseases (e.g., heart disease and breast cancer), and injuries and violence (e.g., motor vehicle crashes, suicide, and homicide).† Since 2004, the U.S. Preventive Services Task Force (USPSTF) has recommended alcohol misuse screening and brief counseling (also known as alcohol screening and brief intervention or ASBI) for adults aged ≥18 years (3).§ Among adults, ASBI reduces episodes of binge-level consumption, reduces weekly alcohol consumption, and increases compliance with recommended drinking limits in those who have an intervention in comparison to those who do not (3). A recent study suggested that health care providers rarely talk with patients about alcohol use (4). To estimate the prevalence of U.S. adults who reported receiving elements of ASBI, CDC analyzed 2014 Behavioral Risk Factor Surveillance System (BRFSS) data from 17 states¶ and the District of Columbia (DC). Weighted crude and age-standardized overall and state-level prevalence estimates were calculated by selected drinking patterns and demographic characteristics. Overall, 77.7% of adults (age-standardized estimate) reported being asked about alcohol use by a health professional in person or on a form during a checkup, but only 32.9% reported being asked about binge-level alcohol consumption (3). Among binge drinkers, only 37.2% reported being asked about alcohol use and advised about the harms of drinking too much, and only 18.1% reported being asked about alcohol use and advised to reduce or quit drinking. Widespread implementation of ASBI and other evidence-based interventions could help reduce excessive alcohol use in adults and related harms.
Estimation of maximum tolerated dose and minimum efficient dose of BP-C1 in the treatment of stage IV breast cancer patients: A phase I response surface pathway designed study.
Authors: Stig Einride Larsen, Sagita Dewi, Vichien Srimuninnimit, Yen-Shen Lu, Tjakra Manuaba, Steen Lindkaer Jensen
Journal: Journal of Clinical Oncology (2012)

e11022 Background: The aims were to establish a treatment routine and to estimate the Maximum Tolerated Dose (MTD) and the Minimum Efficient Dose (MED) of a novel anti-cancer agent named BP-C1. Methods: The material consists of 15 Stage IV breast cancer patients with a mean age of 51 years. The study was performed as a non-randomized multi-centre trial with between patient 3-level Response Surface Pathway design. BP-C1 was given intramuscularly once daily during 32 days. The given cumulative dose window was 0.16 to 1.12 mg/kg bw, resulting in a starting dose of 0.64 mg/kg bw. The main variable was the National Cancer Institute common toxicity criteria (NCI-CTC) Bethesda. If the increase in toxicity was classified as moderate or less, the next patient in the sequence was allocated to an increased dose. In case of severe toxicity increase, the dose was reduced. Patients receiving cumulative dose of 0.96 mg/kg bw or higher was defines as the high-dose group. Results: Three of the five patients on the first design level recorded unchanged toxicity, one mild and one moderate increased Max NCI-CTC. Of the four patients receiving 0.96 mg/kg bw, three obtained no change and one a mild toxicity increase. The four patients on the third design level received the maximal dose of 1.12 mg/kg bw without any change in Max NCI-CTC. The Sum NCI-CTC increased (p= 0.07) in the low-dose group, but reduced (p=0.09) in the high-dose group. The cumulative dose of BP-C1 was found significantly (p=0.048) and negatively correlated (r = - 0.52) to the increase in toxicity. Only mild to moderate Adverse Events were reported and the prevalence was found largest in the high dose group (p=0.06). In the high-dose group 62.5% of the patients were classified as responders compared to 28.6% in the low-dose group. One of the patients in the high-dose group was classified as complete responder. The development in both Karnofsky Scale of Performance Status and patient wellbeing was found obviously better in the high-dose group. Conclusions: BP-C1 can safely be administrated continuously during a period of 32 days. The MTD seem to be at least 1.12 mg/kg bw and the MED to be 0.96 mg/kg bw.
Genomic Profiles of Bone Marrow (BM) Clonal Plasma Cells (PCs) Vs Circulating Tumor Cells (CTCs) and Extramedullary (EM) Plasmacytomas in Multiple Myeloma (MM)
Authors: Gabriel Bretones, Bruno Paiva, Rafael Valdes-Mas, Diego Alignani, Miguel Garcia, Leire Burgos, Diana Alvarez Puente, Xabier Agirre, Felipe Prosper, Carlos Lopez-Otin, Jesus San Miguel
Journal: Blood (2016)
MRI volumetric analysis of fibroglandular tissue to assess risk of the spared nipple in <i>BRCA 1/2</i> patients who are considering prophylactic nipple-sparing mastectomy.
Authors: Heather Baltzer, Olivier Alonzo, Martin Yaffe, Steven Narod, Kelly A. Metcalfe, Ellen Warner, John Semple
Journal: Journal of Clinical Oncology (2013)

1507 Background: Prophylactic nipple sparing mastectomy (NSM) in BRCA 1/2 mutation carriers is an option for risk reduction but is controversial over concern that residual fibroglandular tissue (FGT) with malignant potential remains in the spared nipple. Since the volume of FGT in the nipple has not been formally evaluated, the objective of this study is to measure the residual volume of FGT in the spared nipple at a standard retroareolar margin (5mm) and identify sources of variability, including a greater margin and patient factors. Methods: A segmentation protocol was applied to breast MRIs from 105 consecutive BRCA 1/2patients. The MRI segmentation quantified volumes for total breast and nipple FGT. The nipple FGT volume was determined by setting the retroareolar margin (depth on MRI). The proportion of FGT in the nipple with 5mm retroareolar margin relative to the breast was calculated as the primary outcome and compared to 10mm margins. Associations between the proportion of FGT in the nipple (5mm) and patient characteristics were examined using uni- and multivariable analyses. Effect size was measured where appropriate. Results: At 5mm and 10mm retroareolar thickness, residual FGT comprised 0.24% (0.02-0.9%) and 0.42% (0.0.2-01.2%), respectively, of the total breast FGT (p &lt; 0.001, Cohen d = 0.03). Smaller breast volume, lower BMI and parity (p &lt; 0.001, p &lt; 0.009, p &lt; 0.009 respectively) were predictive of greater proportion of residual FGT on univariate analysis, while breast volume and parity were predictive with multivariate (R 2 = 0.28, F = 16.5, p &lt; 0.0005). Conclusions: The proportion of FGT remaining in the spared nipple with a 5mm margin is extremely small, suggesting very little added risk over a skin sparing mastectomy. This proportion may be influenced by breast volume and childbearing. Doubling the retroareolar margin statistically increases the proportion, yet this likely does not translate into a clinically meaningful increase and may support a slightly thicker retroareolar margin. Overall, our findings support safety of the current trend toward increased rates of prophylactic NSM performed in the BRCA 1/2 patient population.
Re-biopsy in breast cancer recurrence: Is there really a clinical impact?
Authors: Joelle Collignon, Helene Schroeder, Andree Rorive, Paul Emile Colin, Florence Hanocq, Julien Joskin, Philippe Delvenne, Guy Heinrich Maria Jerusalem
Journal: Journal of Clinical Oncology (2013)

e11549 Background: Several retrospective studies and 3 prospective studies have shown discordance in receptor status between primary tumor and metastasis leading to a treatment modification in about one out of 7 patients. However, some clinicians report unpublished data suggesting that these findings are not observed in all centers. We did prospectively a biopsy at suspicion of first relapse in our center and evaluated the impact of this biopsy on the management of our patients. Methods: Thirty four patients underwent a biopsy between October 2011 and January 2013. Hormonal receptor status was determined by the same IHC methodology for primary and metastatic tissue. Primary tumors were reanalyzed if necessary with our current IHC technique. A change in ER or PgR status was considered clinically significant if quantitative staining changed from &lt;5 % to at least 10% of tumor cells expressing the hormonal receptor or if the opposite is observed. We tested HER2 status by IHC and/or FISH: HER2 3+ or 2+ and FISH positive cases were considered as HER2 positive. Results: Three of 34 patients were considered as screening failure. 1/31 (3.2 %) biopsies showed a benign disease, 2/31 (6.4 %) were non contributive and 5/31 (16 %) showed a metastasis of a second primary tumor. Two of these findings were totally unexpected according to clinical data. Changes in hormone receptor status were observed in 25 % but no change in HER2 status was observed. Time to recurrence was not significantly different between groups with or without modified hormonal status. No clinically significant complication was observed following the biopsies. Only patients presenting a second primary tumor had their management changed based on the new biopsy. Conclusions: We found discordance in hormone receptor status (25 %) but it did not change the treatment. Our study confirms the importance of re-biopsy in order to exclude benign disease or to find metastasis from an unknown and sometimes unexpected second primary tumor. Although our study does neither confirm changes in hormonal receptors resulting in the modification of the treatment strategy nor a change in HER2 status, our data suggest that a new biopsy at first relapse should be performed because unexpected second primaries can be discovered.