tbuckley/cabot-search huggingface dataset:
Negative impact of cachexia during chemotherapy on survival as first-line chemotherapy for metastatic colorectal cancer.
Authors: Kazuki Nozawa, Toshiki Masuishi, Ryosuke Kumanishi, Taiko Nakazawa, Takatsugu Ogata, Yuki Matsubara, Kyoko Kato, Yukiya Narita, Kazunori Honda, Hideaki Bando, Shigenori Kadowaki, Masashi Andoh, Masahiro Tajika, Kei Muro
Journal: Journal of Clinical Oncology (2020)

126 Background: Sarcopenia and muscle loss during chemotherapy (Cx) have a poor prognosis in metastatic colorectal cancer (mCRC). It is unclear whether cachexia during Cx has a survival impact. Methods: mCRC patients (pts) receiving first-line Cx at a single institution between Jan 2010 and Jun 2018 were retrospectively evaluated. Pts receiving doublet Cx with bevacizumab or anti-EGFR agents, ECOG Performance Status (PS) 0–2, and abdominal computed tomography (CT) before and after initiating first-line Cx at least once were included and classified pts into those with (cachexia group) or without (non-cachexia group) cachexia. The skeletal muscle index (SMI) was calculated from the CT cross-section area at L3 divided by the length squared. Muscle loss was defined as a &lt; 5% reduction in the SMI. The association between muscle loss and cachexia during Cx, time to treatment failure (TTF) and overall survival (OS) was determined by univariate and multivariate analysis including muscle loss, primary tumor location, ECOG PS, number of metastatic sites, ALP, WBC, LDH, KRAS status, and BRAF status as independent variables. Results: Of 562 included pts, 185 were eligible and 69 (37%) experienced cachexia. Differences in all patient characteristics such as muscle loss, ECOG PS 2, KRAS mutant, and BRAF mutant (28%, 8%, 32%, and 10% with cachexia group and 27%, 3%, 32%, and 8% with non-cachexia group) were not significant. Median follow-up was 26.8 months. Muscle loss was not associated with TTF (13.3 vs. 15.5 months, HR = 1.05; 95% CI: 0.76–1.45, p = 0.76). OS was shorter (24.4 vs. 29.9 months, HR = 1.23; 95% CI: 0.86–1.76, p = 0.25), but the difference was not significant in univariate and multivariate analysis. However, cachexia group presented significantly shorter TTF [median TTF 11.9 vs. 16.9 m; HR 1.52, 95% CI: 1.12-2.07, p &lt; 0.01; adjusted HR (aHR) 1.53, 95% CI: 1.12-2.11, p &lt; 0.01] and shorter OS (median OS 21.4 vs. 34.1 m; HR 1.81, 95% CI: 1.29-2.55, p &lt; 0.01; aHR 1.97, 95% CI: 1.38-2.81, p &lt; 0.01) than non-cachexia group. Conclusions: Cachexia during Cx may have a negative impact on survival in pts with mCRC.
What drives recommendations for practice?
Authors: Helen Macdonald
Journal: BMJ (2020)

Recommendations for practice can bring clarity, controversy, or confusion. Much depends on the interpretation of limited evidence, the role of commercial influence, and recognition of cultural change.

The BMJ has published two guidelines on subclinical hypothyroidism in the past 12 months whose recommendations differ. A Rapid Recommendation we published last year (doi:10.1136/bmj.l2006) was based on a systematic review and meta-analysis of 21 trials of thyroxine. Its panel strongly recommended against treating subclinical hypothyroidism in most adults, because they found high quality evidence that thyroxine made no important difference …
Can the light of immunometabolism cut through “brain fog”?
Authors: Mady Hornig
Journal: Journal of Clinical Investigation (2020)

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a highly debilitating disease with heterogeneous constitutional and neurological complaints. Infection-like symptoms often herald disease onset, but no pathogen or immune defect has been conclusively linked. In this issue of the JCI, Mandarano et al. illuminate bioenergetic derangements of ME/CFS T cell subsets. CD4+ and CD8+ T cells had impaired resting glycolysis. CD8+ cells additionally showed activation-related metabolic remodeling deficits and decreased mitochondrial membrane potential; a subset had increased resting mitochondrial mass. Immune senescence and exhaustion paradigms offer only partial explanations. Hence, unique mechanisms of disrupted immunometabolism may underlie the complex neuroimmune dysfunction of ME/CFS.
Results of the JAVELIN Gastric 100 phase 3 trial: avelumab maintenance following first-line (1L) chemotherapy (CTx) vs continuation of CTx for HER2− advanced gastric or gastroesophageal junction cancer (GC/GEJC).
Authors: Markus H. Moehler, Mikhail Dvorkin, Mustafa Ozguroglu, Min-hee Ryu, Alina Simona Muntean, Sara Lonardi, Marina Nechaeva, Arinilda Silva Campos Bragagnoli, Hasan Senol Coskun, Antonio Cubillo Gracián, Toshimi Takano, Rachel Wong, Howard Safran, Gina M. Vaccaro, Narikazu Boku, Ilaria Conti, Janet Hong, Huiling Xiong, Julien Taieb, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2020)

278 Background: We report the primary analysis of JAVELIN Gastric 100, which compared avelumab (anti–PD-L1) maintenance after 1L CTx vs continued CTx in patients (pts) with GC/GEJC. Methods: In this global, open-label, phase 3 trial (NCT02625610), eligible pts had previously untreated, unresectable, locally advanced/metastatic (LA/M) HER2− GC/GEJC. Pts without progressive disease (PD) after 12 weeks of 1L oxaliplatin/fluoropyrimidine induction were randomized 1:1 to avelumab 10 mg/kg Q2W switch maintenance or continued CTx, stratified by region (Asia vs non-Asia). Primary endpoint was overall survival (OS) post induction in all randomized or PD-L1+ (≥1% of tumor cells, 73-10 assay) pts. Results: 805 pts received induction CTx and 499 pts were randomized (avelumab, n = 249; CTx, n = 250). At data cutoff (Sep 13, 2019), minimum follow-up was 18 months. In the avelumab and CTx arms, median OS post induction/randomization was 10.4 months (95% CI 9.1-12.0) vs 10.9 months (95% CI 9.6-12.4), hazard ratio (HR) 0.91 (95% CI 0.74-1.11; p = 0.1779); 24-month OS rates were 22.1% (95% CI 16.8-28.0) vs 15.5% (95% CI 10.8-20.9), respectively. The HR for OS in PD-L1+ pts (n = 54) was 1.13 (95% CI 0.57-2.23). No OS trend was seen in Asian pts (n = 114; HR 0.90 [95% CI 0.59-1.36]) or other subgroups, except for a potential benefit with avelumab in pts with no metastatic sites at randomization (n = 60; HR 0.52 [95% CI 0.28-0.98]). Progression-free survival was similar between arms (HR 1.04 [95% CI 0.85-1.28]). In the avelumab vs CTx arms, objective response rates (post randomization only) were 13.3% (95% CI 9.3-18.1) vs 14.4% (95% CI 10.3-19.4), and 12-month rates for duration of response were 62.3% (95% CI 40.9-77.9) vs 28.4% (95% CI 13.2-45.7), respectively. Treatment-related adverse event rates (all grades/grade ≥3) were 61.3%/12.8% with avelumab and 77.3%/32.8% with CTx. Conclusions: Avelumab maintenance showed clinical activity and favorable safety vs continued CTx in pts with LA/M GE/GEJC; however, JAVELIN Gastric 100 did not meet its primary objective of demonstrating superior OS in the randomized or PD-L1+ population. Clinical trial information: NCT02625610.
A phase I/II study of nivolumab, paclitaxel, and ramucirumab as second-line in advanced gastric cancer.
Authors: Shuichi Hironaka, Shigenori Kadowaki, Naoki Izawa, Tomohiro Nishina, Takeharu Yamanaka, Keiko Minashi, Kei Muro, Yu Sunakawa, Takeshi Kajiwara, Yuichiro Hayashi, Yutaka Kawakami, Takako Eguchi Nakajima
Journal: Journal of Clinical Oncology (2020)

352 Background: Synergistic anti-tumor effect induced by simultaneous blockade of PD-1 and taxanes, and PD-1 and VEGFR-2 has been reported. A phase I/II study was conducted to investigate the safety and efficacy of nivolumab (Nivo) with paclitaxel (PTX) plus ramucirumab (Ram), which is the standard treatment as the second-line treatment for advanced gastric cancer (AGC). Methods: AGC patients (pts) with measurable lesions, ECOG PS 0-1, and disease progression on the first-line chemotherapy with fluoropyrimidine and platinum were eligible. Pts received Nivo (3 mg/kg on days 1 and 15) combined with PTX (80 mg/m 2 on days 1, 8 and 15) and Ram (8 mg/kg on days 1 and 15) (Level 1), every 4 weeks. After feasibility was evaluated in 6 pts (phase I part), additional 37 pts were enrolled in a phase II part with the primary endpoint of 6-month progression-free survival (PFS) rate. The combined positive score (CPS) is defined as the number of PD-L1 positive cells (tumor cells, macrophages, and lymphocytes) divided by the total number of viable tumor cells. Results: Fourty-three AGC pts were enrolled: median age, 66 years; ECOG PS 1, 48.8%; and CPS ≥1, 60.5%. Dose limiting toxicities were observed in 2 pts in the phase I part and recommended dose was determined as Level 1. ORR was 37.2% (95%CI, 23.0-53.5%): 46.2% (95%CI, 26.6-66.6%) in CPS≥1 pts and 30.8% (95%CI, 9.1-61.4%) in CPS &lt; 1 pts. With a median follow-up time of 16.8 months, 6-month PFS rate was 46.4% (80% CI, 36.4-55.8%) ( P= 0.067): 57.7% (95%CI, 36.8-73.9%) in CPS≥1 pts and 38.5% (95%CI, 14.1-62.9%) in CPS &lt; 1 pts. Median PFS was 5.1 months (95%CI, 4.5-6.5 months). Median survival time was 13.1 months (95%CI, 8.0-16.6 months): 13.8 months (95%CI, 8.0-19.5 months) in CPS≥1 pts and 8.0 months (95%CI, 4.8-24.1 months) in CPS &lt; 1 pts, and 18-months survival rate was 32.1% (95%CI, 18.2-46.8%). Conclusions: Nivo with PTX plus Ram demonstrated promising antitumor activity as the 2nd-line treatment for AGC pts with manageable toxicities. Clinical trial information: UMIN000025947.
Change in neutrophial-to-lymphocyte ratio (NLR) in response to immune checkpoint inhibitor for advanced gastric cancer.
Authors: Yang Chen, Zhi Peng, Jifang Gong, Changsong QI, Xiaotian Zhang, Jian Li, Lin Shen
Journal: Journal of Clinical Oncology (2020)

306 Background: We intended to evaluate the utility of neutrophil-to-lymphocyte (NLR) in advanced gastric cancer patients treated with immune checkpoint inhibitor (ICI). Methods: We examined NLR at baseline and 6 (±2) weeks later in 139 patients between August 2015 and April 2019. Landmark analysis at 6 weeks was conducted to explore the prognostic value of NLR change on progress-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR). Cox and logistic regression models were adjusted for tumor differention, Lauren classification, line of therapy, type of anti-PD-1/PD-L1 therapy, and baseline NLR. Results: Median duration on therapy was 6 cycles. Median NLR was 3.33 (IQR: 2.26-4.84) at baseline and 2.93 (IQR: 1.67-4.83) at week 6. Patients with a higher baseline NLR showed a trend toward lower DCR, shorter PFS, and shorter OS. Higher NLR at 6 weeks was significantly associated with inferior PFS [hazard ratios (HRs) 1.03, 95% confidence interval (CI): 1.00-1.06 ] and inferior OS (HR 1.08, 95%CI: 1.03-1.12). Relative NLR decrease by ≥ 25% from baseline to 6 weeks after ICI therapy was an independent prognostic factor for ORR (OR 8.11,95% CI:2.40-27.4), DCR (OR 20.03, 95% CI: 3.32-121), PFS (HR 0.37, 95% CI: 0.20-0.68), and OS (HR 0.26, 95% CI: 0.10-0.65). Conclusions: Early decline of NLR (and NLR at 6 weeks) were associated with improved clinical outcomes in advanced gastric cancer patients treated with ICI. [Table: see text]
Epidemiologic and Clinical Characteristics of Novel Coronavirus Infections Involving 13 Patients Outside Wuhan, China
Authors: De Chang, Minggui Lin, Lai Wei, Lixin Xie, Guangfa Zhu, Charles S. Dela Cruz, Lokesh Sharma
Journal: JAMA (2020)

This case series uses patient hospital data to summarize the clinical presentation and laboratory and imaging findings of 13 patients with confirmed 2019-nCoV infection admitted to hospitals in Beijing in January 2020.
Prognostic Value of the Index of Microcirculatory Resistance Over Serum Biomarkers in Cardiac Amyloidosis
Authors: Ki Hong Choi, Joo Myung Lee, So Ree Kim, Darae Kim, Jin-Oh Choi, Seok Jin Kim, Kihyun Kim, Jung-Sun Kim, Bon-Kwon Koo, Eun-Seok Jeon
Journal: Journal of the American College of Cardiology (2020)
Surrogate indicators of survival in patients who received neoadjuvant chemotherapy for type 4 and large type 3 gastric cancer in JCOG0501.
Authors: Masanori Terashima, Junki Mizusawa, Hiroshi Katayama, Yoshiaki Iwasaki, Yoshiyuki Kawashima, Takahiro Kinoshita, Souya Nunobe, Hideki Nakatsuka, Takeshi Omori, Mikihito Nakamori, Yuji Akiyama, Hironori Tsujimoto, Seiji Ito, Yukinori Kurokawa, Takaki Yoshikawa, Narikazu Boku, Takeshi Sano, Mitsuru Sasako, Tsuneaki Fujiya
Journal: Journal of Clinical Oncology (2020)

381 Background: Pathological response rate (pRR) is a common endpoint for assessing the efficacy of neo-adjuvant chemotherapy (NAC) in patients with advanced gastric cancer (GC). We performed supplementary analysis to investigate if pRR can be a surrogate endpoint using data from JCOG0501. Methods: Patients with type 4 and large type 3 resectable GC were randomized either surgery plus adjuvant S-1 (arm A) or NAC (S-1 plus cisplatin) plus surgery plus S-1 (arm B) in JCOG0501. Histological type (sig vs non-sig) was evaluated using preoperative biopsy specimen. Cox proportional hazards model was utilized to assess the effects of covariates for overall survival (OS). Pathological response was defined as Grade1b-3 according to the Japanese Gastric Cancer Association grading. Results: Among 286 (147 in arm A and 139 in arm B) patients who underwent surgery, 132 patients with complete pathological data in arm B were evaluated. Macroscopic tumor response (PR) was observed in 47 patients (36%) and pathological response (Grade 0/1a/1b/2/3) was 15/40/30/44/3, respectively. As shown in the table, pathological response was significantly better OS after adjusting other factors (HR, 0.51 [95% CI 0.30-0.87], p = 0.014). Conclusions: pRR may be used as a surrogate endpoint for future clinical trials in type 4 and large type 3 GC. Clinical trial information: C000000279. [Table: see text]
Estimating Urine Albumin-to-Creatinine Ratio from Protein-to-Creatinine Ratio: Development of Equations using Same-Day Measurements
Authors: Robert G. Weaver, Matthew T. James, Pietro Ravani, Colin G.W. Weaver, Edmund J. Lamb, Marcello Tonelli, Braden J. Manns, Robert R. Quinn, Min Jun, Brenda R. Hemmelgarn
Journal: Journal of the American Society of Nephrology (2020)

Urine albumin-to-creatinine ratio (ACR) and protein-to-creatinine ratio (PCR) are used to measure urine protein. Recent guidelines endorse ACR use, and equations have been developed incorporating ACR to predict risk of kidney failure. For situations in which PCR only is available, having a method to estimate ACR from PCR as accurately as possible would be useful.
Investigating sources of inaccuracy in wearable optical heart rate sensors
Authors: Brinnae Bent, Benjamin A. Goldstein, Warren A. Kibbe, Jessilyn P. Dunn
Journal: npj Digital Medicine (2020)

As wearable technologies are being increasingly used for clinical research and healthcare, it is critical to understand their accuracy and determine how measurement errors may affect research conclusions and impact healthcare decision-making. Accuracy of wearable technologies has been a hotly debated topic in both the research and popular science literature. Currently, wearable technology companies are responsible for assessing and reporting the accuracy of their products, but little information about the evaluation method is made publicly available. Heart rate measurements from wearables are derived from photoplethysmography (PPG), an optical method for measuring changes in blood volume under the skin. Potential inaccuracies in PPG stem from three major areas, includes (1) diverse skin types, (2) motion artifacts, and (3) signal crossover. To date, no study has systematically explored the accuracy of wearables across the full range of skin tones. Here, we explored heart rate and PPG data from consumer- and research-grade wearables under multiple circumstances to test whether and to what extent these inaccuracies exist. We saw no statistically significant difference in accuracy across skin tones, but we saw significant differences between devices, and between activity types, notably, that absolute error during activity was, on average, 30% higher than during rest. Our conclusions indicate that different wearables are all reasonably accurate at resting and prolonged elevated heart rate, but that differences exist between devices in responding to changes in activity. This has implications for researchers, clinicians, and consumers in drawing study conclusions, combining study results, and making health-related decisions using these devices.
VOLTAGE-B study: Nivolumab monotherapy and subsequent curative surgery following preoperative chemoradiotherapy in patients with locally recurrent rectal cancer (LRRC) without previous radiotherapy.
Authors: Takeshi Kato, Hideaki Bando, Yuichiro Tsukada, Koji Inamori, Mamoru Uemura, Satoshi Yuki, Yoshito Komatsu, Shigenori Homma, Daisuke Kotani, Shota Fukuoka, Takeshi Sasaki, Yuji Nishizawa, Naoki Nakamura, Masashi Wakabayashi, Motohiro Kojima, Yosuke Togashi, Akihiro Sato, Hiroyoshi Nishikawa, Takayuki Yoshino, Masaaki Ito
Journal: Journal of Clinical Oncology (2020)

100 Background: Chemoradiotherapy (CRT) followed by curative resection in patients (pts) with local recurrence after radical surgery for primary rectal cancer is the preferred strategy if radiotherapy (RT) was not previously performed. In VOLTAGE-A study, nivolumab plus surgery following CRT showed a promising pathologic complete response (pCR) rate of 30% in pts with microsatellite-stable (MSS) advanced primary rectal cancer. The treatment sequence was prospectively investigated in pts with Locally Recurrent Rectal Cancer (LRRC) in VOLTAGE-B. Methods: Pts with pelvic LRRC without previous RT were included. Five cycles of nivolumab (240 mg q2 weeks) plus curative surgery following CRT (50.4 Gy with capecitabine 1,650 mg/m 2 ) were performed. The pCR rate using AJCC tumor regression grading and curative resection rate were key endpoints. Planned sample size in VOLTAGE-B was set 10 pts in an exploratory manner. Results: From May to Oct 2018, 10 pts were included. Median age was 65 and 8 were male. Curative resection was performed in nine pts with MSS. One had a newly diagnosed supraclavicular lymph node metastasis before surgery. As one pt with AJCC grade 0, seven with grade 2, and one with grade 3, were observed, pCR rate was 10%. As of cut-off date of Apr 2019, three pts showing recurrence out of the nine pts were observed. Nivolumab-related adverse events (AEs) were only one pt with grade 1 hyperthyroidism and one with grade 1 erythema. Grade 3/4 surgery-related AEs were observed in six pts, including two pts with ileus and two with pelvic infections. No treatment-related deaths were observed. Conclusions: The pCR rate of 10% with acceptable toxicity was shown in MSS LRRC pts treated with nivolumab plus curative surgery following CRT. Translational research exploring better predictors of efficacies of study treatment are ongoing. Clinical trial information: NCT02948348.
Female representation in clinical trials leading to FDA cancer drug approvals for gastrointestinal (GI) cancers between 2008 to 2018.
Authors: Shehara Ramyalini Mendis, Seerat Anand, Arvind Dasari, Joseph M. Unger, Anirudh Gothwal, Lee M. Ellis, Gauri Rajani Varadhachary, Scott Kopetz, Michael J. Overman, Kanwal Pratap Singh Raghav, Jonathan M. Loree
Journal: Journal of Clinical Oncology (2020)

809 Background: Proportionate representation of women in health research is an area for improvement. This study aims to assess the representation of women in gastrointestinal (GI) cancer clinical trials leading to FDA cancer drug approvals over the past 10 years. Methods: FDA cancer drug approvals between 07/2008-06/2018 were identified and trial reports supporting approvals sourced. The ratio of female to male (F:M) enrollment was compared with F:M cancer incidence in the U.S., and U.S. cancer prevalence and mortality. Results: Although F:M enrollment for all 229 trials leading to FDA cancer drug approvals in this period was similar to overall F:M cancer incidence in the U.S. (0.89 vs 0.86; Odds Ratio for female enrollment (OR) 1.05, 95% Confidence Interval (CI) 1.03-1.06, P&lt;0.0001), in 17 trials that led to drug approvals in GI cancers there was lower F:M trial enrollment compared to cumulative U.S. incidence at those tumor sites (0.55 vs 0.79, OR 0.71, 95% CI 0.68-0.74, P&lt;0.0001). F:M enrollment and U.S. incidence by the main GI tumor sites where approvals occurred is shown in Table. Female enrollment rates were also lower than U.S. female cancer mortality and prevalence rates in these tumor sites (P&lt;0.0001 for all). Female enrollment in GI trials fell between 2008-2013 and 2014-2018 (38 vs 33%, OR 0.80, 95% CI 0.74-0.87, P&lt;0.0001). Conclusions: Although disparity in female enrollment may be improving across combined FDA cancer drug approval trials, underrepresentation of females has persisted in GI cancer trials when compared to F:M cancer incidence, prevalence and mortality in the U.S. More work is required to determine the drivers of this disparity, in order to mitigate it. [Table: see text]
Vitamin D Supplementation during Pregnancy and the Prevention of Childhood Asthma
Authors: Erika von Mutius, Fernando D Martinez
Journal: New England Journal of Medicine (2020)

Asthma is a major cause of illness and health care costs: in 2016, almost 200,000 Americans were admitted to the hospital for an asthma attack, and 40% of them were children (https://www.cdc.gov/asthma/healthcare-use/healthcare-use-2016.htm). It therefore makes sense to consider asthma prevention a major public health priority. In most cases of asthma, the first symptoms occur during the preschool years,1 and even in patients with bona fide adult-onset asthma, deficits in airway function and bronchial hyperresponsiveness could already be detected in early life.2 It is thus not surprising that many asthma-prevention strategies preferentially target the prenatal period or early postnatal life. An . . .