tbuckley/cabot-search huggingface dataset:
Activity of cabazitaxel in temozolomide refractory glioblastoma: Final results of a phase 2 study (C-GBM study; EudraCT 2013-001550-98 NCT 01866449).
Authors: Bernhard Heinrich, Richard F Schlenk, Olaf Lothar Brudler, Simone Edenhofer, Angelika Scheuerle, Ralph Naumann, Regine Mayer-Steinacker, Markus Bangerter, Lars Bullinger
Journal: Journal of Clinical Oncology (2017)

2056 Background: Following progression on Temozolomide (TMZ) glioblastoma (GBM) is a therapeutic challenge with a 6 month survival rate of only ~20-30% and no well-established 2nd line treatments. Methods: We designed a phase II study to assess the efficacy of cabazitaxel, a second generation taxoid, in TMZ-refractory GBM pts (pts). Primary enpoint was response at 12 weeks of treatment. Secondary endpoints were overall survival (OS), quality of life, and pharmacokinetics. The study population were pts with progressive GBM during or within 6 months after TMZ treatment, in whom radiotherapy and surgery was no treatment options. Exclusion criteria were signs of inflammation, an ECOG performance score (PS) &gt; 2, as well as impaired organ function. Patient characteristics: In total, between 2014 and 2016 8 female and 16 male pts were included with a median age of 55 years (range 32-76 years) and a median of 3 previous therapies (range 1-9). Treatment: Cabazitaxel was given at 25mg/m² q3w with G-CSF prophylaxis. Every two cycles response assessment was performed (MRI). Treatment was discontinued in case of i) progressive disease (RANO criteria), ii) PS≥3, or iii) persistent toxicity. Results: Five pts went off study prior to the first MRI assessment due to progressive disease, while 19 of 24 of pts could be evaluated for response after 2 cycles. We did not observe any objective response (i.e. complete or partial remission). In 7 pts a stable disease (SD) was obtained; 12 pts had progressive disease. Of the 7 SD pts, 4 progressed after 4 cycles of treatment and the remaining pts remained in SD for 6, 10 and 12 cycles, respectively. The median OS was 155 days. Toxicity was manageable by G-CSF application in pts with CTC grade 3/4 neutropenia/leukopenia in 12 pts. Non-hematological toxicity CTC grade 3/4 comprised infection (n = 2), diarrhea (n = 2), vaginal bleeding (n = 1) and hypokalemia (n = 1). Conclusions: Cabazitaxel shows only marginal activity in TMZ refractory GBM with a disease stabilization rate following 4 cycles of only 12.5% in heavily pretreated GBM pts and median OS of 155 days. Clinical trial information: NCT 01866449.
A Double-Blind Placebo-Controlled Trial of Granulocyte Colony-Stimulating Factor in Elderly Patients With Previously Untreated Acute Myeloid Leukemia: A Southwest Oncology Group Study (9031)
Authors: John E. Godwin, Kenneth J. Kopecky, David R. Head, Cheryl L. Willman, Catherine P. Leith, Harry E. Hynes, Stanley P. Balcerzak, Frederick R. Appelbaum
Journal: Blood (1998)
The relationship between statins and colorectal cancer stage in the Women's Health Initiative.
Authors: Brian Rutledge, Pinkal M. Desai, Mahmoud Abdel-Rasoul, Rami Nassir, Lihong Qi, Juhua Luo, Simin Liu, Monica Arun, Michael S. Simon
Journal: Journal of Clinical Oncology (2017)

1540 Background: Statins are the most widely prescribed cholesterol-lowering drugs in the United States. The anti-carcinogenic effect of statins may reduce the metastatic potential of cancer cells leading to ‘stage migration’ with users more likely diagnosed with early rather than late stage cancer. We evaluated the relationship between prior statin use and colorectal cancer (CRC) stage at diagnosis in the Women’s Health Initiative (WHI). Methods: The study population included 132,322 post-menopausal women aged 50-79 years, among which there were 2,628 pathologically confirmed cases of insitu (3.3%), local (43.6%), regional (40.4%) and distant (12.7) stage CRC, after an average of 13.9 (SD = 4.7) years of follow-up. To reduce the possibility of detection bias among women more likely to be prescribed statins, we excluded women who did not report a mammogram within 5 years of study entry and who had no health insurance or medical care provider (n = 28,237). Stage was coded using criteria implemented in the Surveillance, Epidemiology and End Results (SEER) Program into early (in situ and local) vs. late (regional and distant) stage disease. Information on statin use prior to diagnosis was collected by self and interviewer-administered questionnaires at baseline and at one, three, six and nine years post-baseline. Self- and interviewer-administered questionnaires were used to collect risk factor information. Hazards ratios (HR) and 95% confidence intervals (CIs) evaluating the relationship between statin use at baseline only, and in a time-dependent manner, and diagnosis of late-stage CRC were computed from multivariable-adjusted Cox proportional hazards analyses. Statistical tests were two-sided. Results: Statins were used by 10,868 women (8%) at baseline. There was no significant relationship between statin use at baseline and late stage CRC cancer (HR = 1.03, 95% CI (0.82-1.30) and no significant association by type of statin or duration of use. In the multivariable-adjusted time-dependent model, use of statins was associated with a reduction in diagnosis of late-stage colorectal cancer (HR 0.79, 95% CI 0.67-0.94, p = 0.007). Conclusions: Prior statin use may have an influence on colorectal cancer stage at diagnosis.
Early neonatal mortality and timing of low risk births
Authors: R. Varma
Journal: BMJ (2001)

Editor—Heller et al's unstated premise that the incidence of perinatal death due to intrapartum asphyxia in low risk pregnancies may serve as a sensitive measure of the quality of peripartum care delivered is appealing.1,2 But their proposition that the observed higher nocturnal perinatal mortality in their selected population arose because of substandard care was not justified.

Firstly, the authors did not do a comprehensive interrogation of index case records. The Confidential Enquiry into Stillbirths and Deaths in Infancy adopts the gold standard method of a multidisciplinary scrutiny of records to ensure accurate diagnosis and quantify substandard care.

Secondly, imprecise selection criteria meant that the sample population was heterogeneous in terms of pregnancy risk and method of delivery. Further bias arose because Heller et al's early neonatal death rate (0.15/1000 births selected) represented only a small fraction of the unstated overall early neonatal death rate (3.1/1000 live births found in a similar population by the Confidential Enquiry into Stillbirths and Deaths in Infancy3).

Thirdly, criteria required before perinatal asphyxia is diagnosed were not adopted.4 Deaths classified as asphyxia related that occurred as a result of hypoxia during labour do not necessarily mean that the hypoxia was preventable.

Better information would have been derived if the crude early neonatal death rate had been reclassified in a pathophysiological cause specific manner (for example, with the amended Wigglesworth classification5) and incorporated birth weight and gestation specific mortality. Such cause specific mortality relations better identify the exact contribution of antepartum and intrapartum risk factors to infant mortality and whether any diurnal variation in their incidence occurs. Case-control analysis of matched cases with similar obstetric and neonatal factors and delivery centres but different delivery times could further show the contribution of delivery time to perinatal death and whether this relation is cause specific.

Pregnancies without substandard care or obstetric risk that incur higher nocturnal perinatal mortality pose a serious concern; they are perhaps a manifestation of the fetomaternal physiology specific to this time that is currently unknown. Antepartum unexplained fetal death might enter into this subgroup. Standards of healthcare delivery are always under inspection (for example, by clinical governance and the media). Comprehensive evaluation, with consideration given to other possible causes, is essential before such “human” issues are drawn into the causality equation for adverse outcome.
Incise and lay open: Single effective surgery for coccygeal pilonidal disease
Authors: K Murugan, AL Gidwani, A Nasir, RJ Brown
Journal: Endoscopy (2005)

Aims: Pilonidal sinus disease is a frequently encountered surgical entity with a varied surgical practice. This study aims to analyse the outcome of different surgical procedures performed for coccygeal pilonidal disease in an attempt to demonstrate the most efficient operation.
Cost-effectiveness of surveillance and prevention strategies in BRCA 1/2 mutation carriers.
Authors: Hideko Yamauchi, Chizuko Nakagawa, Makoto Kobayashi, Yusuke Kobayashi, Toshiki Mano, Seigo Nakamura, Masami Arai
Journal: Journal of Clinical Oncology (2017)

e13051 Background: Cost-effectiveness analysis is important in healthcare, especially in Japan, where preventive measures for carriers of BRCA 1/2 mutations are not covered by health insurance. Methods: We developed Markov models in a simulated cohort of women aged 35–70, and compared outcomes of surveillance with risk-reducing mastectomy at age 35 (RRM), risk-reducing salpingo-oophorectomy at age 45 (RRSO), and both (RRM&amp;RRSO), with quality adjustment. We used breast and ovarian cancer incidence, and adverse event rates from previous studies, adjuvant chemotherapy and hormonal therapy rates from Hereditary Breast and Ovarian Cancer Registration 2015, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology and Ministry of Health, Labour and Welfare, and direct costs in 2016 Japanese yen from St. Luke’s International Hospital and Keio University Hospital. We used preference ratings for both of mutation carriers and controls (without known high risk) from a published study to adjust survival for quality of life (QALYs). Discount rate was 2%. Results: Compared with surveillance, RRSO and RRM &amp; RRSO were dominant (cost-saving and more effective) and RRM was cost effective for BRCA 1 mutation carriers. RRM and RRM &amp; RRSO were dominant, and RRSO was cost effective for BRCA 2 mutation carriers. Among four strategies including surveillance, RRM &amp; RRSO was the most cost effective for BRCA 1 mutation carriers and RRM was the most cost effective for BRCA 2 mutation carriers based on preference ratings of controls. Conclusions: With quality adjustment, all the preventive strategies (RRM, RRSO and RRM&amp;RRSO) were cost effective for BRCA 1 and 2. Using QALYs from the control group, RRM &amp; RRSO for BRCA 1 and RRM for BRCA 2 were the most cost effective. We will use this result to promote insurance coverage for BRCA mutations carriers in Japan.
Correlates to concussion recovery in college athletes: prospective evaluation of pre-injury modifiers and post-injury clinical and neuropsychological assessments
Authors: Margot Putukian, Riegler Kaitlin, Amalfe Stephanie, Echemendia Ruben, Pasquale G. Frisina
Journal: British Journal of Sports Medicine (2017)

Objective valuate relationships among pre-injury modifiers and post-injury assessments on sport-related concussion (SRC) recovery. Design Prospective-correlational. Setting Single University. Participants 208 SRCs; 173 athletes (males=132, females=41). Assessment of risk factors Baseline modified sideline concussion assessment tool (m-SCAT):symptom checklist, Standardised Assessment of Concussion (SAC), modified-Balance Error Scoring System (m-BESS), Generalised Anxiety Disorder scale (GAD-7), Patient Health Questionnaire (PHQ-9), and history of concussion, learning disorder (LD), headaches/migraines, and depression/anxiety. m-SCAT and hybrid neuropsychological tests 48-hours post-injury Outcome measures Days to symptom free (DSF) and return to full play (DFP). Main results Expected concussion modifiers, (gender, prior concussion, LD, headaches/migraines, depression/anxiety, PHQ-9 or GAD-7) were NOT significantly associated with DSF or DFP (p &gt;.05). Although males (M=9.83, SD=12.22) became SF sooner (1.75 days) than females (M=11.58, SD=9.79), Mann-Whitney test indicated that differences for gender were not statistically significant, U=1249, p=0.11 and males (M=21.20,SD=20.75) and females (M=17.33, SD=14.86) didn’t differ significantly on DFP, U=613, p=0.25. ≤48-hours m-SCAT performance Athletes reporting more symptoms and higher symptom-severity score, took more DSF (rs=0.32, p&lt;0.01, rs=0.35, p&lt;0.01, respectively) and DFP (rs=0.19, p&lt;0.05, rs=0.20, p&lt;0.05, respectively). No statistically significant relationship between SAC or m-BESS and recovery existed. Four symptoms positively and significantly correlated with number of DSF and DFP: headache (SF:rs=0.27, p&lt;0.01; FP:rs=0.23, p&lt;0.05), neck-pain (SF:rs=0.36, p&lt;0.05; FP, rs=0.38, p&lt;0.05), feeling slowed down (SF:rs=0.21, p&lt;0.01; FP:rs=0.19, p&lt;0.05), and nervous/anxious (SF:rs=0.28, p&lt;0.01; FP:rs=0.21, p&lt;0.05). Athletes with slower RT on ImPACT took more DSF (rs=0.27, p&lt;0.01) and DFP (rs=0.25, p&lt;0.01). Athletes scoring lower/worse on ImPACT visual-motor speed composite had higher DSF (rs=-0.24, p&lt;0.01) and DFP (rs=-0.35, p&lt;0.01). Conclusions While pre-injury “modifiers” aren’t correlated with clinical recovery, acute assessments after SRC may indicate prolonged recovery. Competing interests None.
Striking age differences of multiple myeloma (MM) diagnosis in patients of Indian and Pakistani descent in the United States compared to native countries.
Authors: Athira Unnikrishnan, Abdullah Mohammad Khan, Preeti Narayan, Maxim Norkin
Journal: Journal of Clinical Oncology (2017)

e13070 Background: Several studies from India and Pakistan have reported a median younger age of MM diagnosis as compared that of western population. The exact reason for the younger age of myeloma diagnosis in this population is not well understood. Methods: We used the SEER database to analyze age of MM diagnosis in subjects of Indian and Pakistani descent in the United States and compared it to the published data of MM diagnosis in India and Pakistan. Patients with ICD—O-3 morphologic codes (9732/3) and race code 15/16/17 identifying Asian Indians and Pakistanis were identified in the SEER registry data (1973-2013). Data on year of diagnosis, race, sex and age were collected. Four published retrospective studies involving local Indians or Pakistanis patients identified using PUBMED. Average Median age and male to female ratio (M: F) was calculated in both groups and compared for any difference Results: 146 myeloma patients of either Indian or Pakistani descent were identified from the SEER registry. The median age of diagnosis was 67 years with a mean age of 66.1 years. The male to female ratio was 1.41. The retrospective studies analyzed had a total of 495 myeloma patients with median age at diagnosis of 56 years and male to female ratio of 2.01, suggesting that multiple myeloma presented almost a decade earlier in native Indian and Pakistani patients compared to their US counter parts. Conclusions: Subjects in India and Pakistan were significantly younger at the time of MM diagnosis as compared to subjects of Indian and Pakistani descent diagnosed with MM in the US suggesting an environmental factor involved with myeloma genesis in subjects living in India and Pakistan. [Table: see text]
Near complete remission of pulmonary metastases in triple negative breast cancer (TNBC) using low-dose immune checkpoint (IC) inhibitors with high dose (HD) interleukin-2 (IL-2) and fever range hyperthermia.
Authors: Ralf Kleef, Ralph W Moss, Attila Marcell Szasz, Arthur Bohdjalian, Tibor Bakacs
Journal: Journal of Clinical Oncology (2016)

e23111 Background: TNBC is more aggressive, has shorter disease-free and overall survival times than other breast cancer subtypes. Due to the lack of personalized therapies interest is increasing for novel strategies in the metastatic setting. Scientific basis:prolonged low dose anti-CTLA-4 and anti-PD-1 IC blockade with HD IL-2 treatment would be safe and effective in patients with high tumor burden. Methods: Diagnosis of a 50-yr old female patient was primary TNBC with lymphadenopathy and disseminated lung metastases. First, an off-label low-dose PD-1 IC inhibitor nivolumab (0.5 mg/kg) with CTLA-4 IC inhibitor ipilimumab (0.3 mg/kg) was administered weekly, over three weeks. This was accompanied by loco-regional hyperthermia with radiofrequency fields (13.56 MHz) 3 times per week (max. output 400 W) over the thoracic region in combination with Vitamin-C (0.5 g/kg) and alpha lipoic acid (600 mg) over three weeks. This was followed by long duration fever range whole body hyperthermia in combination with low dose cyclophosphamide (300 mg/m²) to down modulate Treg cells. Then, a HD IL-2 (54 Mio/m2 as decrescendo regimen) therapy was administered under Taurolidine protection for five days. Results: The patient presented with widespread disease with a Karnofsky score (Ks) of 80%, felt severe pain in the left lateral chest wall during inspiration that became extremely painful during sneezing. She complained about severe shortness of breath (SOB) on exertion, lack of appetite, insomnia, and exhaustion. Six months later, chest X-ray demonstrated near complete remission of pulmonary metastases. SOB on exertion or any other cancer related symptoms vanished, Ks returned to 100%. Conclusions: We assumed that a frequently administered low dose IC blockade would prevent T cell exhaustion and premature apoptosis making main stream HD IL-2 stimulation treatment safer and more effective. Following the success of this woman, we treated seven more patients with disseminated metastases of different origins, who are responding similarly to the presented TNBC case. This combination treatment warrants further studies.
Morbidity of laparoscopic distal gastrectomy with D2 lymphadenectomy compared with open distal gastrectomy for locally advanced gastric cancer: Short term outcomes from multicenter randomized controlled trial (KLASS-02).
Authors: Hyuk-Joon Lee, Woo Jin Hyung, Han-Kwang Yang, Sang Uk Han, Young-Kyu Park, Ji Yeong An, Wook Kim, Hyoung-Il Kim, Hyung-Ho Kim, Seung Wan Ryu, Hoon Hur, Seong-Ho Kong, Gyu Seok Cho, Jin-Jo Kim, Do Joong Park, Keun Won Ryu, Young Woo Kim, Jong Won Kim, Joo-Ho Lee, Min-Chan Kim
Journal: Journal of Clinical Oncology (2016)

4062 Background: Although lots of benefits of laparoscopic gastric cancer surgery have been reported, strong evidences of laparoscopic surgery are still limited, especially in locally advanced gastric cancer which requires extensive lymph node dissection. Herein, we report the short term clinical outcomes of KLASS-02, a multicenter randomized controlled trial comparing laparoscopic distal gastrectomy (LDG) with D2 lymphadenectomy compared with open distal gastrectomy (ODG). Methods: The enrollment criteria include histologically confirmed gastric adenocarcinoma with cT2-4a and N0-1. Primary end-point was relapse free 3-year survival. Secondary end-points included 30-day morbidity, 90-day mortality, postoperative pain, and recovery. Results: A total of 1,050 patients were randomly assigned to LDG (n = 526) or ODG group (n = 524) between November 2011 and April 2015. After excluding patients who received bypass or no surgery, 1,011 patients were analyzed for modified intention-to-treat analysis. Estimated blood loss was significantly less in LDG (155.3 ml) than in ODG (231.2 ml, p < 0.001). Total number of retrieved lymph nodes was comparable between groups (LDG = 46.6 vs. ODG = 47.4, p = 0.46). Lengths of both resection margins were comparable between groups. The 30-day overall complication rate was 16.4% in LDG and 24.3% in ODG with statistical significance (p = 0.002). Postoperative analgesics use and patients’ reported pain visual analog scale was less in LDG than in ODG. First day of flatus was shorter in LDG (3.53 d vs. 3.71 d, p = 0.027) and post-operative hospital stay was shorter in LDG (8.1 d vs. 9.3 d, p = 0.003). Mortality rate within 90 postoperative days was comparable between groups (0.38% in LDG vs. 0.57% in ODG). Conclusions: LDG with D2 lymphadenectomy for locally advanced gastric cancer has benefits of less complication rate, faster recovery, and less pain without compromising oncologic safety, compared with open surgery. Clinical trial information: NCT01456598.
Bevacizumab for the treatment of radiation necrosis in melanoma patients.
Authors: Isabella Claudia Glitza, Rodabe Navroze Amaria, Neil Mark D'Souza, Wen Jiang, Jing Li
Journal: Journal of Clinical Oncology (2017)

e13548 Background: Radiation necrosis (RN) can be a late complication of radiotherapy for CNS malignancy, often associated with neurological morbidity. High dose corticosteroids or surgical resection have been the standard of care treatment (tx), but protracted steroid course can lead to significant side effects and surgery is not always feasable. While there is evidence that the anti-VEGF antibody bevacizumab (Bev) can be effective for RN in other cancer types, evidence supporting its use for RN in melanoma patients (pts) is lacking, due to known risk of spontaneous bleeding in melanoma brain metastasis (MBM) and increased bleeding risk with Bev. Methods: We retrospectively identified 6 melanoma pts who received Bev for RN, and demographics, systemic and radiation tx history were obtained. Diagnosis of RN was established by MRI in all pts, and pathology confirmed RN in one pt. Results: Description of the 6 pts identified are shown in Table 1. Conclusions: We present 6 melanoma pts who developed RN after CNS radiation and who were treated with 2-6 doses of Bev. None of these pts developed bleeding, and all pts experienced improvement in symptoms and quality of life, with concurrent improvement of imaging in 5 pts. Our series suggests that in selected melanoma pts Bev may be a safe and effective treatment for RN for MBM and should be evaluated in a prospective setting. [Table: see text]