tbuckley/cabot-search huggingface dataset:
Primary testicular lymphoma: Treatment patterns and survival of 1740 men from the National Cancer Database.
Authors: Fernando Caumont, John Burns, Sydney Akapame, Jing Xie, Christopher R. Porter, John Paul Flores
Journal: Journal of Clinical Oncology (2018)

7555 Background: The standard of care (SOC) for primary testicular lymphoma (PTL) is orchiectomy, chemotherapy (CHT) and radiation (RT) of the contralateral testis regardless of stage. PTL is rare and usually presents in elderly men; we hypothesized that men may not receive SOC and may have worse outcomes. To assess this, we queried the National Cancer Database (NCDB) which includes 70% of newly diagnosed US cancers, to analyze treatment patterns and survival of men with PTL in the rituximab era. Methods: Using NCDB data (2006 to 2013), we searched for men diagnosed with extra nodal lymphoma (N = 109210), primary site testis (N = 1865). Patients were analyzed in 2 treatment groups: 1) CHT + RT (SOC group); and 2) CHT alone, RT alone and orchiectomy alone, grouped as no-SOC. Kaplan-Meier (KM) survival plots were used to investigate 5-year overall survival (OS). Log rank test was used to estimate survival differences between treatments. Results: 1740 men with PTL underwent orchiectomy. Median age was 69. 794 (45.6%) were Stage 1, 217 (12.5%) were Stage 2, 88 (5.1%) were Stage 3, 274 (15.7%) were Stage 4. 367 men (21.1%) had no staging information available and were not included in the survival analysis. 619 (35.5%) received SOC, 692 (39.8%) had CHT alone, 54 (3.1%) had RT alone, and 375 (21.6%) received no further treatment. KM analysis by stage (Table 1) showed 5-year OS was significantly higher in the SOC group vs.non-SOC for Stage 1 (83.8% vs. 66.1%, p < 0.001), Stage 2 (78.2% vs. 58.7%, p = 0.003) and Stage 4 (64.3% vs. 54.5%, p = 0.001). Stage 3 patients receiving SOC had a non-significant trend toward survival advantage (74.1% vs 60.7%, p = 0.07). Conclusions: This study represents the largest PTL cohort reported to date and is reflective of current treatments. These data show that most US PTL patients do not receive guideline-recommended SOC, and OS is significantly worse across stages for those that do not receive SOC, highlighting the need for improved management of PTL 5-year OS analysis by stage. Stage SOC* No-SOC* P-values Survival (%) Alive (N) Dead (N) Survival (%) Alive (N) Dead (N) I 83.9 260 50 66.1 320 164 < 0.001 II 78.3 54 15 58.8 87 61 0.003 III 74.1 20 7 60.7 37 24 0.07 IV 64.4 56 31 54.6 102 85 0.001 *SOC: Standard of Care
Results of a comprehensive pharmacogenetic analysis of dihydropyrimidine dehydrogenase in patients treated with fluoropyrimidines and patterns of polymorphisms partially related to treatment tolerability.
Authors: Marzia Del Re, Marta Schirripa, Angela Michelucci, Marta Cubelli, Silvia Magagna, Santino Minichillo, Fotios Loupakis, Paolo Simi, Claudio Zamagni, Alfredo Falcone, Romano Danesi
Journal: Journal of Clinical Oncology (2012)

e13057 Background: Metabolic clearance of fluoropyrimidines is highly dependent on the rate-limiting enzyme dihydropyrimidine dehydrogenase (DPD). Deficiency of DPD is associated with drug accumulation and severe toxicities. The DPD gene (DPYD) is highly polymorphic; however, except the G&gt;A mutation in the splicing consensus sequence of intron 14 (IVS14+1G&gt;A), which is responsible of severe enzyme impairment, the association of other variants with adverse reactions is unclear. Therefore, this study was aimed at examining the prevalence of DPYD variants in patients with toxicities and in subjects with good tolerability to fluoropyrimidine-based regimens. Methods: Patients affected by colorectal, breast and head/neck cancers requiring standard treatment with 5-FU or capecitabine in combination with other cytotoxic agents (irinotecan, oxaliplatin, cyclophosphamide or methotrexate) and/or antibodies (cetuximab or bevacizumab) were enrolled: 224 suffered from grade ≥2 non-hematological and ≥3 hematological toxicities (CTCAE v. 4) and 61 control patients developed adverse events to an extent not requiring dose-delay or reduction (i.e., &lt;2 non-hematological and &lt;3 hematological toxicities). DNA was extracted from blood and used to screen patients for known DPD variants (IVS14+1G&gt;A, 496A&gt;G, 1601G&gt;A, 1627A&gt;G, 1896T&gt;C, 2194G&gt;A and 2846T&gt;C) by automatic sequencing. The study was approved by local Ethics Committee. Results: A complex pattern of DPYD variants was identified in both cohorts; the following genotypes were detected in patients with severe toxicities vs controls: 496AG+GG: 24.1 vs 21.3%; 1601GA: 12.5 vs 1.6%; 1627AG+GG: 37.1 vs 32.8%; 1896TC+TT: 6.25 vs 8.2%; IVS14+1GA: 4.9 vs 0%; 2194GA: 25.9 vs 9.8; 2846AT: 1.3 vs 0%. Conclusions: Although there was a higher prevalence of DPYD variants in patients with severe toxicities, their presence also in subjects with good tolerability suggest that their role needs to be re-evaluated, with the exception of IVS14+1GA and 2846AT which were found only in patients with poor tolerability. This study was supported in part by a grant from AIRC to R. Danesi.
Serum b-cell maturation antigen levels to predict progression free survival and responses among relapsed or refractory multiple myeloma patients treated on the phase I IRUX trial.
Authors: Sean Bujarski, Camilia Soof, Haiming Chen, Mingjie Li, Eric Sanchez, Cathy S Wang, Marsiye Emamy-Sadr, Regina A. Swift, Kian J. Rahbari, Saurabh Patil, Tanya M. Spektor, James R. Berenson
Journal: Journal of Clinical Oncology (2018)

e24313 Background: B-cell maturation antigen (BCMA) is expressed on plasma cells among patients (pts) with multiple myeloma (MM). We have previously shown that the half-life of soluble BCMA is much shorter than sM-protein, and can be used to monitor the course of disease for these pts. We examined if baseline and changes in sBCMA levels during cycle 1 can predict progression-free survival (PFS) and best response among pts enrolled on the IRUX 1504 phase 1 trial evaluating ruxolitinib, lenalidomide and methylprednisolone for relapsed or refractory (RR) MM pts. Methods: Serum (s) was obtained weekly during the first cycle (C1) and first day of the second cycle (C2D1) and monthly thereafter from pts enrolled on the IRux 1504 trial from February 2017 to January 2018. sM-protein levels were also measured weekly, and sBCMA levels were determined using an ELISA (R&D Systems; Minneapolis, MN). Kaplan-Meier analysis was used to assess differences in PFS based on baseline sBCMA levels. We also determined the relationship between changes in sBCMA at C1D8 and best response as determined by IMWG criteria. All pts samples were obtained following proper informed consent in accordance with the Declaration of Helsinki. Results: Twenty-two MM patients (IgG [n = 12], IgA [n = 4], free light chain only [n = 6]) were evaluated. Patients with a baseline sBCMA value in the highest quartile (range, 578.9 – 2211.4 ng/mL) had a significantly shorter PFS than those in the lowest three quartiles (range, 29.3 – 532.9 ng/mL; median PFS: 5.1 vs. 1.12 mo; P= 0.0017). For 80% of pts, the % change in sBCMA on C1D8 accurately predicted their best response. Importantly, all pts that experienced ≥ 50% decrease in sBCMA on C1D8 achieved ≥ PR, and all pts that experienced ≥ 25% increase achieved either an SD or progressed within two cycles. These results were not seen with sM-protein, as pts with evaluable sM-protein did not experience ≥ 25% change in these levels. Conclusions: We have shown that baseline sBCMA levels in MM pts predict PFS among RRMM pts enrolled on the phase I IRUX trial, and that % changes in sBCMA unlike sM-protein on C1D8 are predictive of best responses achieved later in the pts' treatment course.
Spatial Architecture and Arrangement of Tumor-Infiltrating Lymphocytes for Predicting Likelihood of Recurrence in Early-Stage Non–Small Cell Lung Cancer
Authors: Germán Corredor, Xiangxue Wang, Yu Zhou, Cheng Lu, Pingfu Fu, Konstantinos Syrigos, David L. Rimm, Michael Yang, Eduardo Romero, Kurt A. Schalper, Vamsidhar Velcheti, Anant Madabhushi
Journal: Clinical Cancer Research (2018)

The presence of a high degree of tumor-infiltrating lymphocytes (TIL) has been proven to be associated with outcome in patients with non-small cell lung cancer (NSCLC). However, recent evidence indicates that tissue architecture is also prognostic of disease-specific survival and recurrence. We show a set of descriptors (spatial TIL, SpaTIL) that capture density, and spatial colocalization of TILs and tumor cells across digital images that can predict likelihood of recurrence in early-stage NSCLC.The association between recurrence in early-stage NSCLC and SpaTIL features was explored on 301 patients across four different cohorts. Cohort D1 (n = 70) was used to identify the most prognostic SpaTIL features and to train a classifier to predict the likelihood of recurrence. The classifier performance was evaluated in cohorts D2 (n = 119), D3 (n = 112), and D4 (n = 112). Two pathologists graded each sample of D1 and D2; intraobserver agreement and association between manual grading and likelihood of recurrence were analyzed.SpaTIL was associated with likelihood of recurrence in all test sets (log-rank P < 0.02). A multivariate Cox proportional hazards analysis revealed an HR of 3.08 (95% confidence interval, 2.1-4.5, P = 7.3 × 10-5). In contrast, agreement among expert pathologists using tumor grade was moderate (Kappa = 0.5), and the manual TIL grading was only prognostic for one reader in D2 (P = 8.0 × 10-3).A set of features related to density and spatial architecture of TILs was found to be associated with a likelihood of recurrence of early-stage NSCLC. This information could potentially be used for helping in treatment planning and management of early-stage NSCLC.See related commentary by Peled et al., p. 1449.
How to improve the lymph node detection and staging accuracy in gastric cancer patients: A randomized controlled trial in single center.
Authors: Zengwu Yao, Lixin Jiang
Journal: Journal of Clinical Oncology (2017)

e15577 Background: To evaluate the effects of carbon nanoparticles by subserosa injection and different Lymph node retrievals by surgeon or pathologist in improving the positive and total lymph node detection and staging accuracy in patients who undergone the standard D2 gastrectomy. Methods: We collected 200 gastric cancer patients who undergone the standard D2 radical lymph node resection gastrectomy from November 2013 to November 2014 in Gastrointestinal Surgery Ward of Yantai Yuhuangding Hospital. The cases were randomly devidided into 4 groups (N = 50): Pathologist group(PA), surgeon group(SU), surgeon plus carbon nanoparticles group(SU+CN), pathologist plus carbon nanoparticles group (PA+CN) . The number of lymph nodes and the proportion of TNM stages were calculated respectively. Results: In the positive and total number of lymph nodes in all cases, it is significantly higher in Group SU than Group PA (3.64±4.32 VS 2.63±3.45),( 25.46±5.24 VS 20.23±6.32),Group SU+CN than Group PA (4.56±3.86 VS 2.63±3.45 ),(30.76±8.42 VS 20.23±6.32), Group PA+CN than Group PA(3.83±2.09 VS 2.63±3.45),(24.98±6.01 VS 20.23±6.32), Group SU+CN than Group SU(4.56±3.86 VS 2.63±3.45),(30.76±8.42 VS 25.46±5.24), Group SU+CN than Group PA+CN(4.56±3.86 VS 3.83±2.09),( 30.76±8.42 VS 24.98±6.01) (P &lt; 0.05). The proportion of each TNM stage is significantly different in Group SU VS Group PA, Group SU+CN VS Group PA, Group PA+CN VS Group PA, Group SU+CN VS Group SU, Group SU+CN VS Group PA+CN(P &lt; 0.05), while it is similar in Group PA+CN VS Group SU(P &lt; 0.05). The highest proportion of Stage I and II and the lowest proportion of Stage III is in Group PA, and in Group SU+CN by contrary. Multivariate analysis shows carbon nanoparticles by subserosa injection and lymph node retrievals by surgeon are independent factors. Conclusions: Carbon nanoparticles by subserosa injection and lymph node retrievals by surgeon could be used as independent factors to improve the number of positive and total lymph nodes in standard D2 radical lymph node resection gastrectomy. It may also improve the accuracy of pathological staging of gastric cancer patients. Clinical trial information: ChiCTR-TRC-14876411.
Pre-treatment echocardiogram abnormalities and left ventricular function in pediatric patients with new diagnosis of leukemia or lymphoma.
Authors: Carolyn M. Wilhelm, May Ling Mah, Randal S. Olshefski, Olga Toro-Salazar, Robert Gajarski, Kan Hor
Journal: Journal of Clinical Oncology (2016)

10540 Background: Patients who receive radiation and cardiotoxic chemotherapy are predisposed to heart failure and coronary artery disease. Consensus statements recommend baseline echocardiogram with continued monitoring following chemotherapy. The purpose of this study is to define frequency of structural and functional abnormalities on pre-treatment echocardiogram. Methods: A single center retrospective chart review of patients diagnosed with leukemia or lymphoma Jan 2009 - Mar 2015 was performed. Pre-treatment echocardiograms were reviewed for structural abnormalities, valvar leak, left ventricular size, fractional shortening (FS) by 2D M-mode measurement, ejection fraction (EF) by 2D-biplane Simpson’s method, and presence of pericardial effusion. Given the wide range of normal values for FS across age groups, Z scores were utilized for age-normalization. Results: In total, 208 patients (61% male) with average age of 10 years (3 mos-20 yrs) were included. Echocardiogram was performed on average 3 days prior to chemotherapy. Significant abnormalities included 4 mild mitral regurgitation, 4 aortic insufficiency (3 mild and 1 moderate), 29 pericardial effusions (18 trivial, 7 small, 3 moderate, and 1 large), and 3 mild aortic root dilation. EF measurements in 110 patients were ≥ 70% in 22 patients and ≤ 55% in only 2 patients. FS Z scores in 204 patients measured > 2 in 44 patients and < -2 in 4 patients. In the sub-population of patients with EF ≥ 70%, 9 were febrile, 19 were anemic, and 2 were on positive pressure ventilation at the time of echocardiogram. None were on inotropic support. Conclusions: Although baseline echocardiograms are performed for functional analysis, very few patients have decreased function pre-treatment. Hyperdynamic state, valvar regurgitation, and pericardial effusion are more common. The implications of hyperdynamic state in these patients are currently unknown, but may be a useful surrogate for illness severity at time of presentation. Future studies are warranted to establish the predictive value of baseline hyperdynamic function in regards to impact of cardiotoxic therapies and may affect interval of longitudinal evaluation.
Comparison of efficacy and tolerability of weekly adjuvant chemotherapy for colorectal cancer (CRC) using folinic acid with fluorouracil dosed at 425 mg/m<sup>2</sup> or 370 mg/m<sup>2</sup>.
Authors: Michael B. Jameson, Nicola Jane Lawrence, Ian C. Kennedy, Michelle Anne Head, Sanjeev Deva
Journal: Journal of Clinical Oncology (2016)

e15134 Background: Adjuvant chemotherapy (chemo) for CRC using fluorouracil (5FU) and folinic acid (FA) was proven equally effective and less toxic when administered weekly (“QUASAR” regimen) rather than daily for 5 days every 4 weeks (“Mayo” regimen). However survival in the QUASAR trial, using 5FU 370 mg/m2 and L-folinic acid 25mg weekly for 30 weeks, appeared inferior on indirect comparison to other trials using the Mayo regimen dosing 5FU at 425 mg/m2. Two NZ centres adopted the QUASAR regimen but each used a different 5FU dose (370 mg/m2 and 425 mg/m2) with DL-folinic acid 50mg weekly. This facilitated comparison of efficacy and tolerability of this regimen at each 5FU dose. Methods: Patients with non-metastatic CRC who started adjuvant weekly 5FU and FA chemo at Auckland City Hospital (ACH) or Waikato Hospital (WH) between 2001 (2002 at ACH) and 2004 were retrospectively identified from institutional databases and included in the analysis. Data was gathered on patient and tumour characteristics, duration of adjuvant chemo and survival. Reliable ethnicity data was not available. Results: The table shows patient (pt) and tumour characteristics. Death data was updated to January 2016. Rectal cancer pts who required chemoradiation mostly received it post-operatively. Adjuvant chemo was planned for 30 and 28 weeks duration (20 and 16 weeks after chemoradiation) at WH and ACH respectively. 75% and 69% of colon cancer pts and 59% and 65% of rectal cancer pts received all planned chemo doses at WH and ACH respectively. Survival at 5 years for all pts was 71% and 70%, and for stage 3 pts 67% and 69%, at WH and ACH respectively. Actuarial survival was not significantly different between hospitals by log-rank analysis. Conclusions: The QUASAR regimen achieved similar outcomes and tolerability regardless of 5FU dose used. Characteristic Waikato Auckland Patients 301 286 Gender Female 129 134 Age Median (range) years 66 (25–85) 63 (23–89) Primary Rectum/colon 83/218 67/219 Tumour grade 1/2/3/unknown 17/167/56/61 32/198/43/13 TNM stage I/II/III 1/58/242 1/52/233 Chemoradiation + chemo 73 46 Chemo only 228 240 Days to starting chemo 69 (17–152) 56 (12–173)
Optimization of Routine Testing for MET Exon 14 Splice Site Mutations in NSCLC Patients
Authors: Clotilde Descarpentries, Frédéric Leprêtre, Fabienne Escande, Zoulika Kherrouche, Martin Figeac, Shéhérazade Sebda, Simon Baldacci, Valérie Grégoire, Philippe Jamme, Marie-Christine Copin, David Tulasne, Alexis B. Cortot
Journal: Journal of Thoracic Oncology (2018)
Feasibility of cancer treatment without blood transfusion in Jehovah’s Witnesses.
Authors: Rachael Chang, Shawgi Sukumaran
Journal: Journal of Clinical Oncology (2018)

e18554 Background: The management of Jehovah’s Witnesses (JW) who have oncological problems presents many different challenges both at the therapeutic and ethical level due to refusal of blood and blood products. Relevant information on managing JW with cancer is limited. We conducted a systematic review to evaluate different therapeutic strategies applied to JW patients and their impact on the clinical cancer treatment outcomes. Methods: A comprehensive search of Medline, Embase, Pubmed and Cochrane Database was conducted to identify all data related to patterns of care offered to JW patients and treatment related outcome. Prospective and retrospective analysis and case reports were included. Results: A total of 4 Prospective, 9 retrospective studies and 42 case reports (n = 498 patients) were identified. There were 103 cases of lymphoma and 290 cases of solid tumours (gynaecological and prostate cancer being most common). Treatment consisted of surgery (n 193), chemotherapy (n 270), radiation (n 5) and stem cell transplant (n 202). There was substantial variation amongst JW patients regarding acceptable blood products and procedures. Out of 496 JW, only 4 consented for blood transfusion and 116 agreed for minor blood components (plasma, albumin, Factor VII) at baseline. 3 received platelets, 2 factor VII and 9 received blood transfusion in life threatening emergencies. Erythropoietin proved effective in 364 patients for optimising haemoglobin for optimal treatment delivery. Grade 3/4 adverse events were observed in 66 patients (mainly major bleed and severe anaemia) and 9 (1.8%) died due to refusal of blood products. 40 JW had suboptimal treatment due to unacceptable levels of pancytopenia. However 84%(420/498) patients completed the planned treatment. Conclusions: JW patients with cancer can be safely treated without blood/blood products support majority of the time. However treatment pathways need to be prospectively defined for this group of patients.
TCT-144 Impact of baseline left ventricular ejection fraction on clinical outcomes following transcatheter aortic valve replacement for severe aortic stenosis
Authors: Osung Kwon, Duk-Woo Park, Sun Hack Lee, Sangwoo Park, Tae oh Kim, Yong-Hoon Yoon, Sang Yong Om, Minsoo Kim, Hanbit Park, Sang-Cheol Cho, Euihong Ko, Kyusup Lee, Do-yoon Kang, Pil Hyung Lee, Jung-Min Ahn, Soo-Jin Kang, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Seong-Wook Park, Seung-Jung Park
Journal: Journal of the American College of Cardiology (2018)
P05.48 The data base of adult medulloblastomas patients: the experience of Italian Association of Neuro-oncology (AINO)
Authors: A Silvani, P Gaviani, A Pace, G Simonetti, M Caffo, T Ius, M Possanzini, M A Teriaca, G Panzarasa, A Salmaggi, R Rudà
Journal: Neuro-Oncology (2018)

Medulloblastoma is a rare disease in adult patients, it accounts for 6 % of the Posterior Fossa Tumors. Large, trials are often impossible and also access to biospecimens may be problematic Two years ago, during the spring meeting of AINO in Turin we planned an online web-data base on rare tumours of CNS. We decided to start our work with medulloblastoma, as example of multidisciplinary treatment for a rare tumour without codified guidelines. To simplify data collection we chose to include in the data base only the patients treated over the past five years Of the 225 clinicians- centres emailed; 32 (14 %) responded, 27 respondents identified their medical specialties: 11 medical neuro-oncologists, 8 radiation oncologists, 7 neurosurgeons, 1 neurologist 11 centres entered the data in the dbase During the last 5 years, 11 centres reported treated patients for a total of 53 patients 31 Male. Median age at surgery was 35 (17–80). Symptomatic hydrocephalus was found in 50 % of patients. Postoperative residual tumour was found in 10 patients, in 6 pts the residual tumor was less than 1.5 cm square, In 2 pts more than 1,5 cm square Fore other two patients the residue volume was missing. VPS was placed on 3 pts. Positive CFS was found in 3 patients but post op spinal tap was performed only in 20 pts. In eight patients the histological definition was limited to the diction of medulloblastoma non other specified In six patients SHH mutation was found High-risk disease defined as residual disease, metastatic dissemination or large cell- anaplastic histology we defined 14 patients but we have incomplete staging or missing information in 5 pts. After surgery Craniospinal radiotherapy was given to 92 % patients and only 2 had only cranial radiotherapy due to their low PS and the 85 years old patient was not treated. A boost into the posterior fossa was given to almost all patients. X Patients were treated also by chemotherapy and regimens used varied considerably. Recurrence take place in 25 patients, in 10 out of these patients as leptomenigeal dissemination. At recurrence 4 Pts were re-operated on. The radiotherapy re-treatment was administered in one patient. Six Patient were treated with Temozolomide as salvage treatment, plus intrathecal chemotherapy. The data collected on patients and their disease characteristics were consistent with the literature. Similar also relative incidence of different histological subtypes, risk status and tumour surgery. The data are partial due to quite low number of patients included at the moment in d-base. We have extended the observation period up to 10 years and we also have started to insert patients in a prospective way opening the study to the SIN and SINCH members.