tbuckley/cabot-search huggingface dataset:
Where’s my doctor? the impact of the primary oncologist’s visit with their hospitalized patients.
Authors: Brianna R. Bakow, Fred Schiffman, Anthony E. Mega
Journal: Journal of Clinical Oncology (2019)

6603 Background: Continuity of care is a cornerstone of the patient-practitioner relationship and patient satisfaction. The inpatient continuity visit (ICV), a face-to-face patient-provider interaction, involves a discussion regarding hospital course and care goals and decisions. We theorize that the ICV influences patient satisfaction. Previously, patient satisfaction has been related to patient perception of physician conduct, including communication skills. Currently, there are no studies investigating the impact of an ICV on inpatient oncology patients on a hospitalist service. Objectives: To assess the relationship between the ICV and patient satisfaction. We hypothesized that one or more visits by the outpatient oncologist would enhance satisfaction of oncology inpatients. Methods: Subjects (N=82) were comprised of adult inpatients on the oncology unit at Miriam Hospital, a teaching hospital of the Alpert Medical School of Brown University. All participants had an oncologist at the hospital based cancer center. A survey, given at discharge, included a 5-point Likert scale ranging from greatly worsened to greatly improved to assess the impact of the ICV on patient satisfaction. Results: Of 82 participants, 46 reported a visit by their outpatient oncologist. Forty-two (91.3%) reported that this visit either greatly or somewhat improved satisfaction with their hospital stay, while 8.7% reported no impact. Of patients whose oncologist visited once, 94.4% reported either greatly or somewhat improved satisfaction compared to 89.3% who had more than one visit. Out of 36 subjects who did not receive a visit, 16.7% reported that the lack of visit either greatly or somewhat worsened their hospital stay, while 83.3% reported no impact. Conclusions: Our study suggests that an ICV improves satisfaction of care in cancer patients on a hospitalist service. Furthermore, one of every six subjects who did not receive an ICV reported a negative impact on satisfaction. Results highlight a possible intervention to the discontinuity of care that may be perceived by patients. While the practicality of this intervention requires evaluation, the efficacy of a single continuity visit to improve satisfaction is reassuring.
Screening of <i>BRCA2</i> mutated men for detection of prostate cancer: Preliminary results from a national high volume cancer center.
Authors: Monica Zuradelli, Nicolo' Buffi, Paolo Bianchi, Carla Barbara Ripamonti, Monica Barile, Paolo Casale, Alberto Saita, Giovanni Lughezzani, Rodolfo Hurle, Nadia Lo Iacono, Giorgio Ferruccio Guazzoni, Massimo Lazzeri, Armando Santoro
Journal: Journal of Clinical Oncology (2019)

e16567 Background: Up to 10% of cases of Prostate Cancer (PCa) are hereditary. Germline pathogenic mutations in BRCA2 gene confer the highest risk (2.5 to 8.6 fold in men ≤ 65 yr). Beyond periodic Prostate Specific Antigen (PSA) dosage and digital rectal examination (DRE), a targeted screening for carriers is still undefined. Prostate Health Index (PHI), a combination of the tPSA, fPSA and proPSA tests, may be a more accurate biomarker than PSA only to detect PCa. We evaluated how to better screen BRCA2 mutated men for PCa. Methods: We reviewed the genealogical trees of all women tested positive for germline BRCA2 pathogenic mutation at our clinic. We offered targeted BRCA2 mutational analysis to all first/second degree relative men between 40 and 69 yr. A targeted screening program (annual PSA and PHI dosages and DRE) was proposed to all men tested positive. In case of PSA and/or PHI values out of range ( &gt; 4ng/ml and &gt; 20, respectively) we proceeded with a multiparametric Magnetic Resonance Imaging (mpMRI) and fusion biopsy of suspected lesions. Results: From June 2008 to October 2018 610 breast/ovarian cancer patients had BRCA test: 35 (5.7%) tested positive for BRCA1 pathogenic mutation, 32 (5.2%) for BRCA2 pathogenic mutation. From October 2017 90 relatives were checked for the familial mutation and 24 (27%) (12 women, 12 men) tested positive for BRCA2 mutation. All the 12 men (median age 48 yr, IQR 44 to 60) accepted to join our screening program. During the first year all men had negative DRE. Median PSA was 0.70 (IQR 0.43 to 1.02), median PHI was 17.56 (IQR 11.85 to 24.06). One patient with out of range PHI value already had mpMRI resulted negative. During the second year 4 men underwent screening so far: they had negative DRE. Median PSA was 0.57 (IQR 0.38-0.77), median PHI was 16.88 (IQR 11.87-21.90). Two men had PHI out of range and will undergo mpMRI. Conclusions: An accurate review of the genealogical trees of breast/ovarian cancer BRCA2 mutated patients allows to identify male relatives potentially carriers of the same mutation. These men have a high lifetime risk of PCa and require an appropriate screening, currently absent. Our approach may be leveraged as proof of concept of selection and screening program in carriers of BRCA2 mutations.
Efficacy and safety of Crizotinib in patients with ALK positive non small cell lung cancer (NSCLC): Real-world findings.
Authors: Cristina Azpitarte Raposeiras, Noemi De Dios Alvarez, Jorge Garcia, Maria Carmen Areses Manrique, Natalia Fernández Núñez, Francisco J. Afonso Afonso, Margarita Amenedo, Nazaret Quiroga Veiga, Victor Cebey, Martin Lazaro Quintela, Jose-luis Firvida, Begoña Campos Balea, Juan Ruiz Bañobre, Vanesa Varela Pose, Sara Agraso Busto, Manuel Constenla
Journal: Journal of Clinical Oncology (2019)

e20636 Background: First or second line crizotinib has shown greater efficacy in clinical trials than chemotherapy in patients with NSCLC ALK positive and it was the first approved ALK inhibitor. However, there are limited data describing the use of crizotinib and its outcomes in real-world settings. Methods: This is a retrospective, observational study of patients crizotinib treated ALK positive metastatic NSCLC, who received treatment between 1 January 2013 and 30 november 2018. The primary objective was progression free survival (PFS); secondary objetives were overall survival (OS), response rates and toxicity. Results: Fifty-eight patients with NSCLC ALK+ were recollected, 33 women and 25 men. The median age was 61 years (25-88); 46.6% were never smokers, 31% were former smokers. The majority (96.6%) had confirmed adenocarcinoma histology and 25.9% had brain metastases at inicial treatment. Crizotinib was used as first line 55.2% and second line in 37.9%. Progression disease was the most frequent reason of discontinuation of crizotinib (74%) and in 5 patients was discontinued because of toxicity. The most frequent toxicities were edemas (37.9%), increased transaminases (27.5), diarrhea (24%) and nauseas (20%). Grade 3-4 toxicities were present in 4 cases with increase transaminases, 1 case of neumonitis and 2 patients with diarrhea. The response rate was 63.8%. The median PFS was 12.66 months (95% CI :7.95- 17.38) and median OS was 23.36 months (95%CI: 16.29-30.44).In patients with brain metastases (15) the response rate was 46.6% and median OS decrease to 15.36 months (95%CI: 0.1-30.8). Conclusions: Our findings indicate that the results of crizotinib in the real world are consistent or sightly improved with prior clinical trial in PFS and OS, despite our sample includes patients for first line and second/later line crizotinib and ¼ of patients had brain metastasic at crizotinib initiation.
DNA-supramolecule conjugates in theranostics
Authors: Kun Chen, Ting Fu, Weidi Sun, Qin Huang, Pengge Zhang, Zilong Zhao, Xiaobing Zhang, Weihong Tan
Journal: Theranostics (2019)

The elegant properties of deoxyribonucleic acid (DNA), such as accurate recognition, programmability and addressability, make it a well-defined and promising material to develop various molecular probes, drug delivery carriers and theranostic systems for cancer diagnosis and therapy.In addition, supramolecular chemistry, also termed "chemistry beyond the molecule", is a promising research field that aims to develop functional chemical systems by bringing discrete molecular components together in a manner that invokes noncovalent intermolecular forces, such as hydrophobic interaction, hydrogen bonding, metal coordination, and shape or size matching.Thus, DNA-supramolecule conjugates (DSCs) combine accurate recognition, programmability and addressability of DNA with the greater toolbox of supramolecular chemistry.This review discusses the applications of DSCs in sensing, protein activity regulation, cell behavior manipulation, and biomedicine.
Nature of coexisting thyroid autoimmune disease determines success or failure of tumor immunity in thyroid cancer
Authors: Shahnawaz Imam, Pervaiz Dar, Rodis Paparodis, Khalil Almotah, Ahmed Al-Khudhair, Syed Abdul-Moiz Hasan, Nancy Salim, Juan Carlos Jaume
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Thyroid cancer and thyroid autoimmunity are considered opposite extremes of immune-responses. However, several studies have suggested that thyroid cancer coexists with autoimmune thyroid diseases like Hashimoto Thyroiditis (HT) and Graves disease (GD). We have shown that the risk of developing thyroid cancer is higher in patients with a silent form of autoimmune thyroid disease -Euthyroid Hashimoto Thyroiditis-(EHT). <h3>Methods</h3> We analyzed data from 2633 consecutive patients with GD, HT, EHT and non-Autoimmune Thyroid Disease (Non-AITD) for the presence of Differentiated Thyroid Cancer (DTC). We further investigated the microenvironment, and cellular mechanism of protection from DTC in GD/EHT by ex-vivo aspirating infiltrates from thyroid samples. We also re-constituted in vitro the in-vivo microenvironment to mimic an in-vivo context. We isolated NK cells and differentiated macrophages into M1 and M2 phenotype from healthy human peripheral blood monocytes. <h3>Results</h3> DTC was less frequent/aggressive in GD as compared to EHT or Non-AITD. Intra-thyroidal immune-cell profiling revealed differential Natural Killer (NK) cell activity and macrophage polarization in the settings of GD versus EHT. In GD, NK-cells were activated, and macrophages showed M1-like phenotype whereas, in EHT, NK-cells were less active and macrophages displayed M2-like phenotype. Furthermore, in vitro co-cultures of NK-cells with differentiated macrophage subsets revealed that the presence of activated NK (NA) cells favors M1 macrophages, boosts macrophage action and amplifies the innate defense mechanisms. Moreover, co-culture of M2 macrophages with NA, increases the cytotoxicity of NK-cells and favors a pro-inflammatory microenvironment that reverts the anti-inflammatory M2 towards pro-inflammatory M1. <h3>Conclusion</h3> Surveillance innate immune-cells like Natural Killer (NK) cells and macrophages are complementary to each other in their actions. We discovered here that activated NK-cells in the background of the thyroid autoimmune disease, GD, drive macrophage differentiation to the M1/killer phenotype which in turn is cytotoxic to cancer cells and down regulates the M2/repair phenotype. Understanding the molecular basis of macrophage-NK cell interface in Thyroid Cancer, ETH and GD will open new vistas for immunopathology and therapeutic intervention. Macrophages/innate immunity can be modulated from M2 to M1 phenotype to help treat thyroid cancer as naturally done by GD.
Female fertility preservation (FP) at pediatric cancer centers: A report from the Children’s Oncology Group (COG).
Authors: Jennifer Levine, Gwendolyn P. Quinn, James Klotsky, Joanne Frankel Kelvin, Brooke Cherven, Elyse Bryson, Sameeya Ahmed-Winston, Natasha Frederick, Julienne Brackett, Lillian Meacham, David Robert Freyer, Christopher Dvorak, Eric Jessen Chow
Journal: Journal of Clinical Oncology (2019)

11567 Background: Preserved fertility after cancer is a priority for female survivors and their families. Embryo/oocyte cryopreservation are standard of care (SOC) for post-pubertal females. Experimental ovarian tissue cryopreservation (OTC) is the only current option for pre-pubertal girls. We surveyed COG sites about their FP infrastructure and practices. Methods: A REDcap survey was emailed to one individual previously identified as knowledgeable about FP or the Principal Investigator at each COG site. Site specific factors associated with outcomes were determined using logistic regression. All study procedures were IRB-approved. Results: Responses were received from 144 of 220 sites (65%). Discussions about fertility at diagnosis were reported as routinely held with all females “at risk” of infertility, all post pubertal females, and all females at 113 (78%), 94 (65%), and 65 (45%) of sites respectively. Embryo/oocyte cryopreservation was offered at 95 (70%) institutions and independently associated with large (&gt;120 new patients/year) sites (OR 6.0 95%CI 1.6-22.8) and presence of a FP navigator/team (OR 4.7 95%CI 1.7-13.5). OTC was offered at 64 (48%) sites: 34 (25%) by referral to another institution, 18 (13%) under an IRB protocol, and 12 (9%) as a clinical service. OTC accessibility was associated with large sites (OR 3.2 95% CI 1.1-8.9) and a FP navigator/team (OR 3.2 95%CI 1.4-7.0). A total of 102/133 (77%) sites use gonadotropin releasing hormone analogues (GnRHa) for any indication; 90 (68%) for menstrual suppression, 75 (56%) with the goal of ovarian suppression for fertility preservation, and 27 (20%) for contraception. Conclusions: Variation in FP services exists across COG. Discussion of infertility risk is not universal. The availability of OTC at treating institutions is limited. The presence of an FP navigator/team is a modifiable factor associated with greater likelihood of accessing SOC and experimental options. Despite conflicting evidence and lack of endorsement from professional societies, GnRHa’s are commonly used for FP. These survey results suggest FP services remain inadequate but highlight opportunities for improvement and areas of needed research.
Selection of patients for stereotactic body radiation therapy (SBRT) or (bi)lobectomy (L) for the treatment of cT1-T2N0M0 NSCLC by the risk of node involvement using readily available preoperative factors.
Authors: Molly Griffin, Christine Hebert, Rick Voland, John M. Varlotto, Malcolm DeCamp, John Charles Flickinger, Suhail M. Ali, Debra Maddox, Lacey McIntosh, Jennifer Baima, Karl Uy, Ferian Lou, Mark Maxfield, Paulo Oliveira, Isabel M Emmerick, Thomas J. Fitzgerald, William Vincent Walsh
Journal: Journal of Clinical Oncology (2019)

e20055 Background: Currently it is not known whether certain patients with early-stage non-small cell lung cancer(NSCLC) would be better served with stereotactic body radiation (SBRT) or surgery. The purpose of our investigation is to see if patients who are at higher risk of node involvement based upon pre-operative factors would be preferentially served with (bi)Lobectomy(L). Methods: The NCDB was queried for the years 2004-2014 to find patients with cT1-T2N0M0 NSCLC (excluding lepidic adenocarcinoma and their variants) &lt; 5cm treated via L or SBRT(N = 16,722). Recursive partition analysis was used in the L group to develop high, medium, and low risk node involvement groups in those patients having complete node assessment (10 or more nodes examined) by American College of Surgeons commission on cancer quality care measures(ACOS coc), N = 83,890. The L and SBRT groups were then propensity matched based upon factors associated with OS to assess whether there was an OS benefit for either the L or SBRT treatments by node risk category. OS was calculated by log-rank testing. Results: The high, medium, and low risk categories had an average risk for node involvement of 20.12, 11.3, and 4.57%, respectively. The low risk group was defined as tumors &lt; 21mm for all squamous cell carcinomas(SQ) and adenocarcinoma(AD) in the right upper lobe only. High risk categories were associated tumors &gt; 21 mm in the RUL in white Hispanics; and ages &lt; 60yr old for SQ, large cell ca, and NSCLC-NOS; and &gt; 21mm with non-RUL location and &lt; 55yr old. OS was significantly better in patients treated by L for the high, medium, and low risk groups with all p-values of &lt; 0.0001. Conclusions: When patients undergo a complete lymph node dissection by the ACOScoc quality measures and have (bi)lobectomy, their OS is superior to patients undergoing SBRT whether they are at high, low or medium risk of lymph node involvement.
Deep learning segmentation of kidneys with renal cell carcinoma.
Authors: Kevin Yin, Chengfeng Liu, Michelle Bardis, Jeremy Martin, Hannah Liu, Alexander Ushinsky, Justin Glavis-Bloom, Chanon Chantaduly, Daniel S. Chow, Roozbeh Houshyar, Peter Chang
Journal: Journal of Clinical Oncology (2019)

e16098 Background: Renal cell carcinoma (RCC) is the most common kidney malignancy and the eighth most common cancer overall, with more than 60,000 new cases and nearly 15,000 deaths in the United States each year. The majority of RCC is asymptomatic and detected incidentally on computed tomography (CT) scans performed for other indications. Multiple prior studies have highlighted the potential for a lesion to be missed or mischaracterized. Artificial intelligence (AI), the mimicking of human cognition by computers, has promise for improving radiological accuracy. Convolutional neural networks (CNNs), a type of AI, apply a feed-forward design to an artificial neural network. Multi-layered CNNs thus have application in biomedical imaging and radiology. In this study we describe an approach for automatic localization and segmentation of the kidneys on contrast enhanced CT scan. Methods: This IRB approved retrospective study included patients who were diagnosed with RCC and had an abdominal CT scan with IV contrast from 2011 to 2019. For each abdominal CT scan, the kidneys and any renal lesions were manually segmented by a board-certified abdominal radiologist on the coronal post-contrast phase of the CT scan. Two CNNs were developed and trained to segment the kidneys automatically. Initially, the CNN implemented a regression algorithm that predicted a 3D bounding box around each kidney. Subsequently, the second CNN used a 3D/3D U-Net algorithm that received the bounding cube as its input and outlined the kidney as an output. After training, the CNN algorithms were assessed by a Sørensen-Dice coefficient. Results: The first CNN that predicted a 3D bounding box around each kidney was trained on 127 abdominal CT exams. The second CNN that segmented the kidneys with RCC was trained on 259 bounding boxes that encompassed the kidneys. The Sørensen–Dice coefficient for segmentation of the kidneys with RCC was 0.92. Conclusions: These results demonstrate that two CNNs can be used in succession to segment the kidneys with RCC on a coronal CT image with high accuracy. Moreover, as the subjects included patients with RCC, medical renal disease, and cystic renal disease, the outcome further supports the role of CNN in evaluation of complex cases rather than pristine training sets. Future work will focus on segmentation of RCC lesions.
Cancer driver genes in prostate cancer from young men.
Authors: Simone Maistro, Camila dos Santos Xavier, Pedro Adolpho MP Serio, Maria Lucia Hirata Katayama, Rosimeire Aparecida Roela, Maria A. A. Koike Folgueira
Journal: Journal of Clinical Oncology (2019)

e16586 Background: Although prostate carcinoma is the most frequent cancer in older man, it is a rare disease in young adults. Search for global knowledge of the cancer genome is of great importance for diagnosis and/or treatment of these patients. Our goal was to identify the mutation profile of prostate carcinoma from young adults aged ≤49 years, using in silico tools. Methods: In silico analysis of somatic variants derived from exome or genome sequencing, deposited in the COSMIC or CBIOPORTAL database or in published manuscripts was performed. Data was searched for cancer driver genes catalogued in Cancer Gene Census (CGC) or Candidate Cancer Gene Database rank A or B (CCGD) and DNA repair genes. Results: 46 prostate adenocarcinoma samples from patients aged between 23-49 years (median 44.5) were included. A median of 15 variants per patient (minimum: 2 and maximum: 343) was detected. The most frequent events were C to T transitions, representing a median percentage of 39% of the substitutions. A total of 160 genes were affected by pathogenic mutations (splice site, nonsense, frame shift ins, frame shift del, nonstop, in frame del). Ten tumors presented pathogenic variants in at least one cancer driver (CGC); 3 tumors presented SNVs in two CGC. The most frequently altered cancer causing genes (CGC) were MUC16 (17%); TP53 (8%), SPOP (8%), XPC, SYNE1, IDH1, CDMD3, ANAPC1, AHNAK (6%). Seven tumors presented pathogenic variants in at least one in driver candidate from CCGD rank A, and 3 tumors in CCGD rank B. Single nucleotide variants affecting genes involved in DNA repair were found in 35% samples and one tumor presented variants in genes involved in BER, NER, FA, DDC and HRR. Variants in TP53 and XPC wer3e detected in 3 tumors. Conclusions: In prostate carcinoma from young men a wide range of cancer causing genes may be altered, including MUC16 and TP53. Variants in DNA repair genes may be found in 35% of the samples.
Hereditary cancer genetic testing among patients with pancreatic cancer.
Authors: Nassim Taherian, Jennifer Saam, Katie Larson, Johnathan M. Lancaster, Jennifer Permuth
Journal: Journal of Clinical Oncology (2019)

4134 Background: Pancreatic cancer (PC) is typically diagnosed at a late, untreatable stage, with a 5-year survival rate of only ~8%. Genetic testing for individuals with PC may aid in therapy decisions, as those with a germline or somatic pathogenic variant (PV) in a DNA-repair gene may benefit from PARP inhibitors. In addition, germline genetic testing for unaffected family members can identify high risk individuals who may be appropriate for surveillance studies. We assessed the results of hereditary cancer genetic testing among individuals with a personal history of PC and evaluated several possible risk factors. Methods: Individuals with PC who had germline testing for 25-29 cancer-susceptibility genes between September 2013 and November 2018 were included in this analysis (N = 1,676). Clinical characteristics were obtained from provider-completed test request forms and included personal cancer history (PHx), family cancer history (FHx), and age at diagnosis. Results: Overall, 12.6% (212/1676) of patients with PC carried a PV, most commonly in BRCA2 (3.8%), ATM (2.7%), and PALB2 (1.2%). PVs were more common in men and for individuals who had a PHx of additional cancer(s) (see Table). Age at PC diagnosis did not impact the positive PV rate. The PV positive rate was elevated among individuals with PC and at least two relatives with PC (15.1%) and for individuals with a FHx of cancer at an early age (14.2%). The PV positive rate remained &gt; 10% regardless of nearly all other FHx characteristics evaluated, including the absence of any FHx (see Table). Conclusions: In this cohort, a substantial proportion of individuals with a PHx of PC carried PVs, regardless of age at diagnosis and personal and family cancer history. [Table: see text]