tbuckley/cabot-search huggingface dataset:
Worldwide Secular Trends in Age at Pubertal Onset Assessed by Breast Development Among Girls
Authors: Camilla Eckert-Lind, Alexander S. Busch, Jørgen H. Petersen, Frank M. Biro, Gary Butler, Elvira V. Bräuner, Anders Juul
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> The initial clinical sign of pubertal onset in girls is breast gland development (thelarche). Although numerous studies have used recalled age at menarche (first menstruation) to assess secular trends of pubertal timing, no systematic review has been conducted of secular trends of thelarche. <h3>Objectives</h3> To systematically evaluate published data on pubertal timing based on age at thelarche and evaluate the change in pubertal onset in healthy girls around the world. <h3>Data Sources</h3> A systematic literature search was performed in PubMed and Embase of all original peer-reviewed articles published in English before June 20, 2019. <h3>Study Selection</h3> Included studies used clinical assessment of breast development in healthy girls and used adequate statistical methods, including the reporting of SEs or CIs. The quality of the articles was evaluated by assessing study design, potential sources of bias, main characteristics of the study population, and methods of statistical analysis. <h3>Data Extraction and Synthesis</h3> In accordance with PRISMA guidelines, all articles were assessed for eligibility independently by 2 authors. Weighted regression analysis was performed using a random-effects model. <h3>Main Outcomes and Measures</h3> Studies examining age at thelarche (development of Tanner breast stage 2) in healthy girls. <h3>Results</h3> The literature search resulted in a total of 3602 studies, of which 30 studies fulfilled the eligibility criteria. There was a secular trend in ages at thelarche according to race/ethnicity and geography. Overall, the age at thelarche decreased 0.24 years (95% CI, −0.44 to −0.04) (almost 3 months) per decade from 1977 to 2013 (<i>P</i> = .02). <h3>Conclusions and Relevance</h3> The age at thelarche has decreased a mean of almost 3 months per decade from 1977 to 2013. A younger age at pubertal onset may change current diagnostic decision-making. The medical community needs current and relevant data to redefine "precocious puberty," because the traditional definition may be outdated, at least in some regions of the world.
Recurrence Rates in Patients With Cervical Cancer Treated With Abdominal Versus Minimally Invasive Radical Hysterectomy: A Multi-Institutional Retrospective Review Study
Authors: Shitanshu Uppal, Paola A. Gehrig, Katherine Peng, Kristin L. Bixel, Koji Matsuo, Monica H. Vetter, Brittany A. Davidson, M. Paige Cisa, Brittany F. Lees, Laurie L. Brunette, Katherine Tucker, Allison Stuart Staley, Walter H. Gotlieb, Robert W. Holloway, Kathleen G. Essel, Laura L. Holman, Ester Goldfeld, Alexander Olawaiye, Stephen L. Rose
Journal: Journal of Clinical Oncology (2020)

To compare the disease-free survival (DFS) between open and minimally invasive radical hysterectomies (RH) performed in academic medical institutions.Retrospective multi-institutional review of patients undergoing RH for stage IA1 (with lymphovascular invasion), IA2, and IB1 squamous, adenocarcinoma, or adenosquamous carcinoma between January 1, 2010 and December 31, 2017.Of 815 patients, open RH was performed in 255 cases (29.1%) and minimally invasive RH in 560 cases (70.9%). There were 19 (7.5%) recurrences in the open RH and 51 (9.1%) recurrences in the minimally invasive group (P = .43). Risk-adjusted analysis revealed that minimally invasive RH was independently associated with an increased hazard of recurrence (aHR, 1.88; 95% CI, 1.04 to 3.25). Other factors independently associated with an increased hazard of recurrence included tumor size, grade, and adjuvant radiation. Conization before surgery was associated with lower recurrence risk (aHR, 0.4; 95% CI, 0.23 to 0.71). There was no difference in OS in the unadjusted analysis (HR, 1.14; 95% CI, 0.61 to 2.11) or after risk adjustment (aHR, 1.01; 95% CI, 0.5 to 2.2). Of 264 patients with tumors ≤ 2 cm on final pathology (excluding those with no residual tumor on final pathology), 2/82 (2.4%) recurred in the open RH group and 16/182 (8.8%) in the minimally invasive RH group (P = .058). In propensity score matching analysis, 7/159 (4.4%) recurrences were noted in the open RH group and 18/156 (11.5%) in the minimally invasive RH group (P = .019). Survival analysis revealed an increased risk of recurrence in the minimally invasive group in propensity-matched cohort (HR, 2.83; 95% CI, 1.1 to 7.18).In this retrospective series, patients undergoing minimally invasive radical hysterectomy, including those with tumor size ≤ 2 cm on final pathology, had inferior DFS but not overall survival in the entire cohort.
Efficacy and safety of second-line nab-paclitaxel plus gemcitabine (nab-P+GEM) after progression on first-line FOLFIRINOX in advanced pancreatic ductal adenocarcinoma (PDAC): Multicenter retrospective analysis.
Authors: Changhoon Yoo, Hyehyun Jeong, Heejung Chae, Jaekyung Cheon, Hong Jae Chon, Hyewon Ryu, Il-Hwan Kim, Jae Ho Jeong, Kyu-Pyo Kim, Baek-Yeol Ryoo
Journal: Journal of Clinical Oncology (2020)

689 Background: FOLFIRINOX is one of standard 1 st -line regimens for patients (pts) with advanced PDAC. However, there is no globally established 2 nd -line regimen after failure of FOLFIRINOX. Although gemcitabine-based regimens are recommended by multiple guidelines and widely used in daily practice, further analysis is needed to reveal the magnitude of clinical benefit with these regimens. Nab-P+Gem is another standard 1 st -line regimen for PDAC, but there are limited data as 2 nd -line therapy in PDAC. Therefore, we conducted multicenter retrospective analysis of 2 nd -line nab-P+Gem after progression on FOLFIRINOX in pts with advanced PDAC. Methods: Between Feb 2016 and Feb 2019, a total of 103 pts with histologically documented PDAC who received nab-P+GEM after progression on 1 st -line FOLFIRINOX were identified among 5 referral cancer centers in South Korea. Results: Median age was 60 years and 50 pts (49%) were male. All but one pts had ECOG performance status of 0-1 at the time of nab-P+GEM. At the time of nab-P+GEM, 25 (24%) and 78 (76%) patients had locally advanced and metastatic disease, respectively. Median overall survival (OS) and progression-free survival (PFS) with nab-P+GEM was 9.8 months (95% CI: 8.9-10.6) and 4.6 months (95% CI: 3.7-5.5), respectively. Among pts with measurable disease (n = 95), partial response and stable disease were achieved in 8 (8%) and 56 (54%), respectively. Median OS from the start of 1 st -line FOLFIRINOX was 20.9 months (95% CI: 15.2-26.6). Most common adverse event of all grade was anemia (77%), followed by neutropenia (60%), fatigue (52%), thrombocytopenia (45%), and peripheral neuropathy (30%). Most common grade 3-4 adverse events were neutropenia (36%), anemia (9%), and peripheral neuropathy (8%). Conclusions: In medically fit pts with advanced PDAC who failed on 1 st -line FOLFIRINOX, nab-P+GEM was effective and well tolerated as 2 nd -line therapy.
Refusal of surgery results in inferior survival in esophageal cancer.
Authors: Matthew Parsons, Randa Tao, Shane Lloyd, Skyler Bryce Johnson, Courtney L. Scaife, Ignacio Garrido-Laguna, Thomas Varghese
Journal: Journal of Clinical Oncology (2020)

364 Background: Trimodality therapy with chemoradiation followed by surgery is the standard of care for non-metastatic esophageal cancer. Some patients refuse surgery and this information is captured in the National Cancer Database (NCDB). We sought to understand factors associated with refusal of surgery in these patients and to compare their survival rates with those who undergo surgery. Methods: Data from the NCDB for patients with pathologically proven non-metastatic esophageal cancer from 2006 to 2013 were pooled and screened. Patients with T1N0M0 disease were excluded. Pearson’s chi-squared test and multivariate logistic regression analyses were used to assess the distribution of demographic, clinical, and treatment factors. After propensity-score matching with inverse probability of treatment weighting, overall survival (OS) was compared between patients who refused surgery and those who had surgery using Kaplan Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling. Results: We found 890 of 18,942 patients (4.6%) refused surgery. Older patients, females, those with squamous histology, patients insured by Medicare and those who received radiation therapy (RT) were more likely to refuse. Patients who had N1 disease, high incomes, those who received chemotherapy and those who lived farther from care were more likely to have surgery. The initial 6 month OS was not significantly different between patients who refused surgery and those who had surgery (93.5% vs 95.1% P= 0.064). However, five-year OS was significantly lower in patients who refused (16.4% vs. 38.4% P&lt; .01). This survival decrement was observed uniquely in patients with both adenocarcinoma and squamous cell carcinoma histology. Among those who refused surgery, the OS decrement was mitigated by increasing RT doses. In those who received over 54 Gy of RT, there was no statistical difference in OS between the groups (HR = 0.84, 95% CI 0.65-1.09). Conclusions: We identified a number of patient characteristics that are related to the refusal of surgery in esophageal cancer. Refusal of surgery was related to a decrease in OS in propensity weighted cohorts. This survival decrement may be mitigated by RT in a dose dependent fashion.
Benefit of oxaliplatin in stage III colon cancer according to IDEA risk groups: Analysis of MOSAIC and C-07 trials.
Authors: Ofer Margalit, Ben Boursi, Manel Rakez, Thierry André, Greg Yothers, Norman Wolmark, Einat Shacham Shmueli, Aimery De Gramont
Journal: Journal of Clinical Oncology (2020)

118 Background: The IDEA pooled analysis compared 3 to 6 months of adjuvant chemotherapy for stage III colon cancer. The overarching goal was to reduce chemotherapy-related toxicity, mainly oxaliplatin-induced neuropathy. Patients were classified into low-risk and high-risk, suggesting low-risk patients may be offered only 3 months of treatment. In our previously published analysis using retrospective data from the National Cancer Database (NCDB) we showed similar benefit for oxaliplatin in both low and high IDEA risk groups. In the current study, we aimed to test our hypothesis using data from the two large clinical trials assessing the benefit of oxaliplatin in the adjuvant setting, namely, MOSAIC and C-07. Methods: Using the MOSAIC and C-07 previously published studies, we identified 1,754 low-risk and 1,302 high-risk individuals with stage III colon cancer, according to the IDEA classification. We used multivariate COX regression to evaluate the magnitude of survival differences between IDEA risk groups, according to oxaliplatin use. The analysis was adjusted for age, primary tumor sidedness, tumor stage, tumor grade and lymph node ratio. Results: Individuals with IDEA low-risk derived overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) benefit from the addition of oxaliplatin to adjuvant chemotherapy, with adjusted hazard ratios (HRs) of 0.78 (0.65-0.94), 0.75 (0.63-0.89) and 0.74 (0.62-0.90). Similarly, individuals with IDEA high-risk derived OS, DFS and RFS benefit from the addition of oxaliplatin to adjuvant chemotherapy, with adjusted HRs of 0.84 (0.71-0.99), 0.81 (0.69-0.95) and 0.82 (0.69-0.97). Conclusions: IDEA risk classification per se does not predict benefit from addition of oxaliplatin to adjuvant chemotherapy in stage III colon cancer, according to analysis of the MOSAIC and C-07 studies. Funding: NCI U10CA-180868, NCI U10CA-180822.
Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate
Authors: Wan-Hsin Wen, Huey-Ling Chen, Tiffany Ting-Fang Shih, Jia-Feng Wu, Yen-Hsuan Ni, Chien-Nan Lee, Lu-Lu Zhao, Ming-Wei Lai, Shu-Chi Mu, Yi-Ching Tung, Hong-Yuan Hsu, Mei-Hwei Chang, M.K. Shyu, H.L. Hwa, Y.N. Su, J.C. Shih, K.H. Chao, Y.C. Chiu, K.C. Chang, C.J. Liu, T.H. Su, D.S. Chen, S.M. Chen, C.C. Lin, P.Y. Lin, W.R. Yang, J.J. Hu, C.K. Yang, Y.K. Chang, K.H. Chen, H.H. Lin, Y.H. Lin, H.J. Chen, H.S. Pan, B.H. Lau, C.L. Lee, P.J. Cheng, Y.L. Chang, H.Y. Chiueh, T.H. Wang, J.J. Hsu, L.M. Lo, C.L. Hsieh, S.W. Cheng, M.S. Tsai, L.H. Lin, B.Q. She, F.S. Peng, Y.C. Lin, C.P. Chen, J.P. Huang, C.Y. Yeung
Journal: Journal of Hepatology (2020)
Clinical utility of comprehensive circulating tumor DNA (ctDNA) testing compared to standard-of-care (SoC) tissue testing in first-line (1L) metastatic colorectal cancer (mCRC) patients (pts).
Authors: Manuel Benavides, Julia Alcaide, Martina Alvarez, Esperanza Torres, Isabel Sevilla, Silvia Gil Calle, Carmen Reyna, Inmaculada Alés, Gema Durán, Roberto Wolman, Mireya Cazorla, Pedro Jimenez Gallego, Irene López, Alexandra Cantero, Ana Godoy, Richard B. Lanman, Iris Faull, Justin Odegaard, Il Jin Kim, Emilio Alba
Journal: Journal of Clinical Oncology (2020)

15 Background: Accurate genotyping is mandatory for the management of mCRC pts. Tissue-based testing is still the SoC; however, is not available for all pts. and may be exhausted by serial testing, resulting in incomplete genotyping. We aimed to establish the validity of comprehensive non-invasive ctDNA testing in 1L mCRC pts for whom SoC tissue genotyping was available. Methods: 1L mCRC pts were tested with a comprehensive ctDNA test (Guardant360), a RAS ctDNA test (OncoBeam), and SoC tissue testing at the time of diagnosis. The primary endpoint was NCCN guideline biomarker discovery rate ( KRAS, NRAS, and BRAF mutations, ERBB2 amplification, and microsatellite instability). Results: In 91 evaluable pts, the biomarker discovery rate was 54.9% (50/91) for SoC tissue testing, 59.3% (54/91) for comprehensive ctDNA testing ( p= 0.0318 for non-inferiority vs. SoC), and 42.9% (39/91) for RAS ctDNA testing (inferiority not rejected vs. SoC). Both comprehensive and RAS ctDNA testing showed high positive agreement (85%, 44/52, and 86%, 31/36) and negative agreement (96%, 268/279, and 93%, 93/100) relative to SoC tissue testing at the gene level. Expanding genotyping beyond KRAS codon 12/13 mutations increased biomarker discovery rate by 56% for tissue testing (50/91 vs. 32/91, McNemar’s p&lt; 0.0001) and by 64% for comprehensive ctDNA (54/91 vs. 33/91, McNemar’s p&lt; 0.0001). Turnaround time was significantly shorter for comprehensive ctDNA testing vs. SoC tissue testing (mean 11.7 days vs. 23.0 days, paired T-test p= 0.0002). On retrospective analysis, 92% of biomarker-positive pts would have been identified at 2 weeks using the comprehensive ctDNA test for initial genotyping with reflex to tissue for biomarker-negative pts, whereas initial use of SoC tissue testing would have identified only 85% of positive pts at 4 weeks (Fisher’s exact p&lt; 0.0001). Conclusions: As previously reported for lung cancer, comprehensive ctDNA testing in 1L mCRC identifies at least as many biomarker-positive pts as SoC tissue genotyping with high concordance to tissue and in half the turnaround time.
Prognostic phenotypic subtypes to predict recurrence and response to adjuvant chemotherapy for colorectal cancer.
Authors: Antonia K. Roseweir, James Hugh Park, Sanne ten Hoorn, Arfon GMT Powell, Susan Aherne, Campbell SD Roxburgh, Donald C. McMillan, Paul G. Horgan, Elizabeth Ryan, Keiran Sheahan, Louis Vermeulen, James Paul, Janet Shirley Graham, Owen Sansom, David Church, Timothy Iveson, Joanne Edwards
Journal: Journal of Clinical Oncology (2020)

205 Background: Histological phenotypic subtypes have been proposed that stratify survival in a discovery cohort of patients with stage I-III colorectal cancer (CRC). However, clinical utility has not been validated nor associations with recurrence and chemotherapy assessed. Therefore, this study assessed prognostic value in patients with stage I-III CRC as well as predictive value for recurrence and chemotherapy response. Methods: Two independent stage I-III CRC patient cohorts were utilized to assess associations between phenotypic subtypes, survival, and recurrence. Stage II-III patients, from the SCOT adjuvant chemotherapy trial, were utilized to assess associations between phenotypic subtypes and adjuvant chemotherapy response. Log rank analysis compared immune and stromal subtypes. Results: In an 867-patient internal cohort, phenotypic subtype stratified patients by disease-free survival (DFS) (HR 2.18 95% CI 2.26-4.47, p &lt; 0.001); independent of stage and location. The stromal subtype also predicted increased local and distant recurrence (p &lt; 0.001). In a 146-patient external validation cohort, phenotypic subtype significantly stratified patients by DFS (HR 3.43 95% CI 1.60-7.35, p = 0.001). In 1343 SCOT trial patients, phenotypic subtype significantly stratified patients by DFS (HR 1.59 95% CI 1.13-2.25, p = 0.010). Furthermore, there was evidence that the effect of regimen depended on phenotypic subtype (p = 0.048), only significantly stratifying DFS in patients receiving FOLFOX (HR 3.73 95% CI 1.58-8.81, p = 0.003) but not CAPOX (HR 0.84 95% CI 0.56-1.26, p = 0.396) adjuvant chemotherapy. Interestingly, the immune subtype associated with improved DFS in patients receiving FOLFOX compared to CAPOX adjuvant chemotherapy (HR 3.40 95% CI 1.41-8.19, p = 0.006). Whereas patients with a stromal subtype trended towards improved DFS in patients receiving CAPOX compared to FOLFOX adjuvant chemotherapy (HR 0.72 95% CI 0.50-1.05 p = 0.088). Conclusions: Histological phenotypic subtypes are an effective independent prognostic classification for patients with stage I-III CRC that can predict response to FOLFOX adjuvant chemotherapy as well as the presence of local and distant recurrence.
An assessment of dose intensity of the TNT approach on outcomes in locally advanced rectal cancer.
Authors: Ashley Elizabeth Glode, Tyler Friedrich, Gurprataap Singh Sandhu, Whitney Herter, Martin McCarter, Ana Luiza Gleisner, Elisa Birnbaum, Steven Arthur Ahrendt, Jon Vogel, Karyn A. Goodman, Tracey E. Schefter, William T. Purcell, Alexis Diane Leal, Gentry Teng King, S. Lindsey Davis, Stephen Leong, Wells A. Messersmith, Christopher Hanyoung Lieu
Journal: Journal of Clinical Oncology (2020)

258 Background: Patients with clinical stage II or III locally advanced rectal cancer may be treated with the total neoadjuvant therapy (TNT) approach; chemotherapy with 4 mths of FOLFOX followed by chemoradiation (chemo/XRT) with capecitabine for 5 wks administered before surgery. We hypothesized that full dose intensity is not necessary for treatment benefit. Methods: A retrospective chart review was conducted on patients with newly diagnosed rectal cancer recommended to receive TNT by the multidisciplinary (multiD) colorectal cancer tumor board at the University of Colorado Cancer Center (UCCC). The primary objective was to evaluate dose intensity of TNT and its impact on response assessed by biopsy and/or imaging (MRI). Results: Between January 31, 2016 and January 31, 2019, 80 patients were recommended the TNT approach for cancer management by the multiD team. Of those, 48 completed their neoadjuvant treatment at UCCC and were included in the analysis. The average age was 55 years (range 23-80) and 61% were male. Thirty-one patients had an ECOG of 0 and 17 had an ECOG of 1. Overall responses were 44% complete response (CR, n = 21), 15% near complete response (nCR, n = 7), 35% partial response (PR, n = 17), and 6% no response (NR, n = 3). See Table for responses seen by dose intensity for chemotherapy. Two patients did not receive their full planned XRT course, and 9 patients had their capecitabine doses held/decreased during chemoradiation. Conclusions: This single center retrospective analysis of patients receiving the TNT approach for rectal cancer provides data supporting that achieving full dose intensity is not necessary to achieve treatment benefit. [Table: see text]
A study looking at different types of severe rashes called acute exanthemas
Authors: O. Deschamps, N. Ortonne, S. Hüe, C. Rodriguez, C. Deschodt, G. Hirsch, A. Colin, L. Grégoire, M.‐H. Delfau‐Larue, O. Chosidow, P. Wolkenstein, S. Ingen‐Housz‐Oro
Journal: British Journal of Dermatology (2020)

Severe rashes, called acute exanthemas (AE), are frequently seen in hospital. The most common type is called maculopapular exanthema (MPE), and another type is pityriasis rosea. The main causes of AEs, especially MPEs, are drugs (delayed hypersensitivity) and viruses (such as HIV, human herpesvirus 6 - HHV6, and measles virus), but for some no cause is identified, which is known as ideopathic. There are no guidelines for which tests (viral investigations) should be carried out. The researchers conducted this study to better describe AE, and to explore the value of investigations into the causes of AE, called cytokinic and metagenomic analysis. 98 patients being seen at the Henri Mondor hospital in France were included. Patients were examined by a medic, received tests for viruses, and skin biopsies (tissue samples) were taken. Patients were classified into five groups: viral group (18 people), drug-induced group (33), drug-induced and viral (5), idiopathic (32) and pityriasis rosea (10). HHV6 was the most common virus found (74%). Analysis looking at levels of proteins called cytokines showed higher levels of a cytokine called interleukin-33 in the idiopathic exanthemas (i.e. the ones with an unidentified cause). This could suggest an environmental factor as a trigger. The study showed for the first time the feasibility of metagenomics analysis (studying the genetic material) in the skin, and the results question whether some of the routine virus tests used are always beneficial. This summary relates to the study: Acute exanthemas: a prospective study of 98 adult patients with an emphasis on cytokinic and metagenomic investigation