tbuckley/cabot-search huggingface dataset:
Should all pancreatic neuroendocrine tumors (PNET) over 1 cm be resected?
Authors: Diana Hsu, Sidney Le, Alex Chang, Austin Spitzer, George Kazantsev, Peter D Peng, CK Chang, Thach-Giao Truong
Journal: Journal of Clinical Oncology (2021)

4108 Background: Pancreatic neuroendocrine tumors (PNET) are a heterogeneous group of tumors that represent 1-2% of all pancreatic neoplasms. Their biologic behaviors are unpredictable with high grade, nodal metastasis, or liver metastasis lending an unfavorable prognosis. Current guidelines recommend resection for functioning tumors and those 2 cm or larger but are less straightforward regarding tumors &lt; 2 cm in size. Previous data show that observation for nonfunctioning tumors &lt; 2 cm can be safe and feasible; however, a significant portion of these patients may have nodal involvement or metastatic disease. Methods: A retrospective review was undertaken to identify patients with pancreatic neuroendocrine tumors treated at Northern California Kaiser Permanente (KP-NCAL) between February 2010 and December 2018. Univariate and multivariate analyses were performed with the log-rank test and Cox regression. Chi-squared test of relevant clinicopathologic factors determined which factors were predictive for overall survival (OS). Results: Mean age was 61 years in our cohort of 354 patients, with 29% over the age of 70. Mean tumor size was 3.43 cm; 32% of tumors were 2 cm or smaller. 51% of the patients had localized disease; 32% of the patients presented with metastatic disease. The pancreatic tail was the most common tumor location (38%), followed by the head of the pancreas (24%). On multivariate survival analysis, stage, location of the tumor, and surgical resection were statistically significant in terms of overall survival ( p&lt;.001). Mean OS for patients with localized and metastatic disease was 93 months versus 37 months ( p&lt;.001). Surgery was utilized in 8.9% of patients with metastatic disease ( p&lt;.001). All patients with PNET smaller than 1 cm in our study group had localized disease only. However, in patients with tumor size between 1 and 2 cm, 11% had nodal or metastatic spread. Conclusions: PNETs are indolent but have malignant potential at any size. In our retrospective study, all of the patients with tumor size &lt; 1 cm had localized disease. For those with PNETs 1-2 cm in size, 11% had nodal or metastatic spread. Based on our findings, we suggest a more aggressive surgical resection size criteria of 1 cm.[Table: see text]
Racial disparity in OncotypeDX score in early stage, hormone receptor positive, HER-2 negative, node negative breast cancers: A systemic review and meta-analysis.
Authors: Yi Lee, Ruolin Liu, Alexis K. Bean, Madison J. Garshasebi, Qasim Jehangir, Jasmeet Kaur, Geetha Krishnamoorthy, Judie R. Goodman
Journal: Journal of Clinical Oncology (2021)

e12555 Background: Oncotype DX Breast Recurrence Score (RS) is the currently used risk-assessment tool for early-stage, hormone receptor-positive, HER-2 negative, node-negative breast cancer in the US. Studies showed inconsistency in RS distribution and treatment among races. Causes may include variations in somatic mutations like Ki-67, which have been reported to express higher in African American (AA) and Asian populations than in Non-Hispanic White (NHW) population, germline mutations in BRCA and TP53, that are not in the RS algorithm, and financial burden of the testing. We analyzed data from different countries to investigate racial disparity in RS. Methods: We searched Medline, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials, indexed from January 2010 to January 2021. More than 85% of studies were conducted in the pre-TAILORx study phase. To include data that are available and better represent different races, we included studies that used the previous cutoff value, low-risk ( &lt; 18), intermediate-risk (18-30), high-risk ( &gt; 30). Retrospective studies using Surveillance, Epidemiology, and End Results or National Cancer Database were excluded to avoid overlap data. A total of 17 studies, 9789 patients from seven countries (US, Japan, China, Taiwan, Kuwait, UAE, Israel) were pooled. The Odds Ratio (OR) was extracted with a 95% confidence interval (CI) for RS distribution and post-RS treatment. Both fixed-effect and random-effect meta-analysis were performed. Results: Among AA and NHW, AA were 1.7 times more likely to have high recurrence score (OR = 1.75; 95% CI = 1.46 - 2.10; P &lt; 0.0001), with no heterogeneity among studies (I2 = 0%, heterogeneity P = 0.59). Asian were 1.59 more likely than NHW to be high-risk using a random effects model (OR = 1.59; 95% CI = 1.06 - 2.40; P = 0.0259). High-risk Asian were two times more likely to receive adjuvant chemotherapy post-RS comparing to NHW (OR: 2.31, CI: 1.07 - 4.98, fixed effect model; OR: 2.85, CI: 0.48, 17.05, random effects model), while high-risk AA were less likely to receive chemotherapy comparing to NHW (OR: 0.74, CI: 0.54-1.01, fixed effect model; OR: 0.73, CI: 0.54-0.99, random effects model). Intermediate-risk Asian and AA were more likely to receive chemotherapy compared to NHW (Asian to NHW; OR: 1.68, CI: 1.16-2.43, with fixed effect model, OR: 1.68, CI: 0.94-3.02, with random effects model; AA to NHW; OR: 1.16, CI: 0.93-1.46 with fixed effect model; OR: 1.06, CI: 0.62-1.79 with random effect model). Conclusions: We identified racial disparity in RS and post-RS treatment. Future research is required to elucidate the causes for AA and Asian receiving higher recurrence scores, a need for tailoring RS cutoffs for different races, and the utilization in adequate post-RS treatment.
Clinical impact of molecular tumor profiling in pediatric, adolescent, and young adult patients with extra-cranial solid malignancies: An interim report from the GAIN/iCat2 study.
Authors: Alanna J. Church, Laura Corson, Pei-Chi Kao, Alma Imamovic-Tuco, Wenjun Kang, Navin R. Pinto, Luke Maese, Theodore Willis Laetsch, AeRang Kim, Susan Colace, Margaret E Macy, Mark A. Applebaum, Rochelle Bagatell, Amit J. Sabnis, Daniel Weiser, Julia Lynne Glade Bender, Samuel Louis Volchenboum, Steven G. DuBois, Wendy B. London, Katherine A. Janeway
Journal: Journal of Clinical Oncology (2021)

10005 Background: Next generation sequencing (NGS) assays are now a standard part of clinical care for many adult solid cancers. The significance of molecular tumor profiling for the care of children with cancer is not well understood.We aimed to determine the clinical impact of identifying genomic alterations by NGS for young patients with relapsed, refractory, or high-risk extracranial solid tumors. Methods: We report on the first 389 participants in a prospective cohort study enrolling patients at 12 institutions with extracranial solid tumors diagnosed at age 30 years or less. Targeted DNA NGS was performed on one or more tumor samples from each patient. Selected patients also had tumors subjected to RNA sequencing. Test results were returned to the treating oncologist and follow-up treatment and response data were collected.Identified genomic alterations were classified according to evidence of impact on diagnosis, prognosis or response to targeted therapy matched to an identified alteration (matched targeted therapy, MTT) using established guidelines. Response to MTT was determined and reported as a response if either there was radiographic response according to RECIST or the duration of therapy was &gt; 4 months. Results: Molecular tumor profiling (MTP) was successful in 345 (89%) patients (mean age 11 years at diagnosis; 65% with sarcoma). Two hundred and ninety-nine patients with MTP results (87%) had one or more alterations of clinical significance. Genomic alterations with diagnostic, prognostic or therapeutic significance were present in 208 (60%), 51 (15%) and 240 (70%) patients, respectively. Of the 240 patients with tumors harboring genomic alterations designated as having therapeutic impact, 23 (11%) had Tier 1 molecular findings. 205 patients were eligible to receive MTT based on having a molecular alteration with therapeutic significance and sufficient follow-up; 31 of these patients (15%) received MTT. Seven patients (23%) receiving MTT responded, 6 of these were kinase fusions. All of the responders received targeted therapy matched to a fusion and 78% of diagnostically significant alterations were fusions. Conclusions: Molecular tumor profiling has a significant impact on diagnosis and treatment recommendations for young patients with extracranial solid tumors. These results emphasize the importance of fusion detection for patients with sarcomas and rare tumors. Clinical trial information: NCT02520713.
Clinicopathological and molecular characteristics of early-onset stage III colon adenocarcinoma: An analysis of 25 studies with 35,713 patients in the Adjuvant Colon Cancer End Points (ACCENT) database.
Authors: Zhaohui Jin, Jesse G. Dixon, Hiral Parekh, Frank A. Sinicrope, Greg Yothers, Daniel G. Haller, Hans Schmoll, Aimery De Gramont, Rachel Kerr, Julien Taieb, Eric Van Cutsem, Chris Twelves, Leonard B. Saltz, Naohiro Tomita, Takayuki Yoshino, Thierry Andre, Amit Mahipal, Richard M. Goldberg, Thomas J. George, Qian Shi
Journal: Journal of Clinical Oncology (2021)

3597 Background: Colon cancer (CC) incidence and mortality have decreased since the 1970s, but the incidence in young adults (20-49 years) is increasing. There are limited data suggesting that, as a group, patients with early onset CRC (eoCC) may have different phenotypic characteristics compared to those with late onset CRC (loCC, age ≥ 50 years). Methods: Individual patient data on 35,713 subjects with stage III CC from 25 randomized studies (recruiting between 1987 and 2009) in the ACCENT database were pooled. The distributions of demographics, clinicopathological features, biomarkers, and outcome data were summarized by age group. Overall survival (OS), disease-free survival (DFS), recurrence free rate (RFR), and survival after recurrence (SAR) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for gender, race, body mass index, performance status, disease stage, grade, risk group, number of lymph nodes examined, disease sidedness and molecular markers. Results: Using a 5% difference between age groups as the clinically meaningful cutoff, patients with stage III eoCC (n = 6246) had similar distributions according to gender, race, PS, risk group, tumor sidedness and T/N stage compared to those with loCC (n = 29467). Patients with eoCC were significantly less likely to be overweight (30.2% vs 36.2%) but more commonly had ≥ 12 lymph nodes resected (69.5% vs 58.7%). The eoCC tumors were more frequently mismatch repair deficient (16.4% vs 11.5%), and less likely to have BRAF V600E (5.6% vs 14.0%), suggesting a higher frequency of Lynch syndrome in eoCC. In univariate analysis, patients with stage III eoCC had significantly better OS, DFS, and SAR; the difference between 3-year DFS and RFR strongly suggests the OS/DFS difference between these the eoCC and loCC may be due to increased competing risks and comorbidities in patients with loCC. In multivariate analysis, age at onset lost its prognostic value when outcome was adjusted for molecular markers. The clear relation between age of onset and KRAS/BRAF status was confirmed in the interaction analysis. Conclusions: Tumor biology was an important determinant of prognosis regardless of patient age. In multivariate analysis age of onset was not a statistically significant determinant of outcome.[Table: see text]
Automated imaging-based stratification of early-stage lung cancer patients prior to receiving surgical resection using deep learning applied to CTs.
Authors: Felipe Soares Torres, Shazia Akbar, Srinivas Raman, Kazuhiro Yasufuku, Felix Baldauf-Lenschen, Natasha B. Leighl
Journal: Journal of Clinical Oncology (2021)

1552 Background: Computed tomography (CT) imaging is an important tool to guide further investigation and treatment in patients with lung cancer. For patients with early stage lung cancer, surgery remains an optimal treatment option. Artificial intelligence applied to pretreatment CTs may have the ability to quantify mortality risk and stratify patients for more individualized diagnostic, treatment and monitoring decisions. Methods: A fully automated, end-to-end model was designed to localize the 36cm x 36cm x 36cm space centered on the lungs and learn deep prognostic features using a 3-dimensional convolutional neural network (3DCNN) to predict 5-year mortality risk. The 3DCNN was trained and validated in a 5-fold cross-validation using 2,924 CTs of 1,689 lung cancer patients from 6 public datasets made available in The Cancer Imaging Archive. We evaluated 3DCNN’s ability to stratify stage I &amp; II patients who received surgery into mortality risk quintiles using the Cox proportional hazards model. Results: 260 of the 1,689 lung cancer patients in the withheld validation dataset were diagnosed as stage I or II, received a surgical resection within 6 months of their pretreatment CT and had known 5-year disease and survival outcomes. Based on the 3DCNN’s predicted mortality risk, patients in the highest risk quintile had a 14.2-fold (95% CI 4.3-46.8, p &lt; 0.001) increase in 5-year mortality hazard compared to patients in the lowest risk quintile. Conclusions: Deep learning applied to pretreatment CTs provides personalised prognostic insights for early stage lung cancer patients who received surgery and has the potential to inform treatment and monitoring decisions.[Table: see text]
Chemotherapy at the end of life: Do we know when to stop?
Authors: Renana Barak, Einav Zagagi Yohay, Barliz Waissengrin, Ido Wolf
Journal: Journal of Clinical Oncology (2021)

e24005 Background: Aggressive end-of-life (EOL) care in cancer patients, especially the administration of chemotherapy, is considered a poor-quality measure, that may divert the treatment course from its' main palliative intent. Decisions taken at EOL are more than evidence-based and often rely on cultural and personal prospects. The universal and free Israeli health care system enables the administration of active treatment without financial or regulatory barriers, even at EOL. Two major advancements in recent years were the implementation of national at-home palliative care services and the approval of targeted and immunotherapies for advanced cancers. We hypothesized that these changes will reduce the use of chemotherapy at EOL. Methods: We sampled consecutive patients treated at a tertiary oncology center who died of advanced cancers between January 2019 to August 2020, and examined the administration of oncologic treatments near EOL. Results: A total of 294 patients were included. Their median age was 67 and 147 were men, 64% (189) of the patients received oncologic treatment during the last month before death, chemotherapy was administered in nearly two-thirds of the cases, 64% (121), followed by immunotherapy (21%, 40), targeted therapy (10%, 19) and a clinical trial (5%, 9). Neither age (P = 0.4), gender (P = 0.9), performance status (P = 0.8), disease duration (P = 0.5), and type of previous oncologic treatment (P = 0.3) were associated with aggressive EOL care. Conclusions: Our data demonstrate that in the absence of any regulatory or financial limitations, an aggressive EOL care may be administered to the majority of patients, regardless of age, performance status or disease duration. Despite increasing use of immunotherapy and targeted therapies and despite its’ toxicity profile and low beneficial effect at this stage, chemotherapy remained the most commonly used type of treatment. These data call for the implementation of educational measures and appropriate universal guidelines, aiming at improving quality of treatment at the EOL, focusing on quality of life rather than the elusive potential of extending life.
Immune evasion in primary testicular and central nervous system lymphomas: HLA loss rather than 9p24.1/<i>PD-L1/PD-L2</i> alterations
Authors: Marthe Minderman, Avital Amir, Willem Kraan, Esther J. M. Schilder-Tol, Monique E. C. M. Oud, Cornelis G. Scheepstra, Arnold L. Noorduyn, Philip M. Kluin, Marie José Kersten, Marcel Spaargaren, Steven T. Pals
Journal: Blood (2021)
Association between estrogen receptor status and Oncotype Dx breast recurrence score.
Authors: Noman Ahmed Jang Khan, Mahmoud Abdallah, Todd W. Gress, Mohamed Farouq Alsharedi
Journal: Journal of Clinical Oncology (2021)

e12519 Background: The 21 gene assay Oncotype Dx Breast Recurrence Score (RS) is currently the standard of care to determine if adjuvant chemotherapy is needed in early stage node negative, hormone receptor positive, HER-2 negative breast cancer. In current American society of clinical oncology (ASCO) guidelines there is little or no benefit of adjuvant chemotherapy in patients older than 50 years whose tumors have Oncotype DX RS &lt;26, and for patients 50 years or less whose tumors have Oncotype DX RS &lt;16. We sought to evaluate the percentage of estrogen receptor (ER) expression as a surrogate measure of determining adjuvant chemotherapy by examining the relationship between ER expression and RS. Methods: We identified 301 patients from years 2015 to 2019 from our cancer registry with early stage hormone receptor positive breast cancer and had oncotype DX testing performed. We divided patients into three groups: Group 1 (ERG1) with ER &lt;10%; Group 2 (ERG2) with ER 10-49%; and Group 3 (ERG3) with ER equal or &gt;50%. We also collected information on tumor size (cm), tumor grade, Nottingham score, and ki-67 percentage. A sub-group analysis was performed for patients &lt; 50 years age (n=30). We compared all continuous variables across ER groups using the Kruskal-Wallis rank test and individual between group comparisons using the Wilcoxon rank sum test. All statistical tests performed utilized a two-tailed p value of &lt;0.05 with the Bonferroni correction for multiple comparisons. Results: Among 301 patients with early stage hormone receptor positive breast cancer, 89.1% were ductal, 7.9% lobular, and 2.9% mixed histology. Median age was 68, 58 and 66 for ERG1, ERG2, and ERG3, respectively (p = 0.41). Median RS was 36 (ERG1), 23 (ERG2), and 16 (ERG3) (p = 0.78 for ERG1 vs. ERG2; p = 0.01 for ERG1 vs. ERG3). As expected, tumor grade, tumor size, and Nottingham score decreased significantly from ERG1 to ERG3. For patients &lt;50 years, median age was 44, 46 and 45 for ERG1, ERG2, and ERG3, respectively (p = 0.75). Median RS was 10 (ERG1), 24 (ERG2) and 18 (ERG3) (p = 0.04 for ERG1 vs. ERG2; p = 0.17 for ERG1 vs. ERG3). Conclusions: We found a significant association between estrogen receptor levels and Oncotype Dx recurrence score (RS) in patients with early stage hormone receptor positive breast cancer patients. Further studies are needed to determine the predictive ability of hormone receptor levels on the outcomes of patients treated for early stage hormone receptor positive breast cancer.
The TIME Trial Network to facilitate rapid clinical trial activation, patient screening, and enrollment in molecularly targeted trials.
Authors: Stephanie OLeary, Megan Shulman, Kevin Ritt, Meghan Degele, Ewelina Protomastro, Jennifer Clauson, Amy Franzen, Ian Churchill Anderson, Minal A. Barve, David N. Oubre, Victor Priego, Angela Saverimuthu, Francis Mark Senecal, Raju Kumar Vaddepally, Kimberly L. Blackwell, Matthew M. Cooney
Journal: Journal of Clinical Oncology (2021)

1563 Background: Clinical trials that require patients to have specific actionable mutations based on next generation sequencing (NGS) present unique problems, such as recruiting patients with rare mutations, low enrollment rates, and distance between patients and trial sites. Such barriers can slow the pace of trial enrollment and delay the development of new therapeutic options. Methods: Tempus Labs has partnered with experienced research sites and pharmaceutical companies with molecularly targeted clinical trials to create the TIME Trial Network. The study portfolio includes pharmaceutical sponsored phase I-III clinical trials across solid tumors and hematological malignancies, targeting actionable mutations. This network was established to ensure rapid just-in-time (JIT) activation of trials by streamlining start-up activities (i.e., execution of CTAs and study budgets/financial exhibits, regulatory paperwork, SIV planning and conduct, drug and study supply shipments, submission to the central IRB, and sponsor-specific requirements). Rapid activation begins upon receipt of an activation form from a site partner. “Site Activated” describes a site that has fulfilled all regulatory, documentation, contracting requirements, and has sponsor approval to screen and enroll patients. Results: In Q4 2020, JIT activations were completed for 6 unique interventional clinical trials across 10 sites in 8 US states in the TIME Trial Network. On average, sites were activated in 9.4 business days. Patients enrolled had rare NGS mutations and were from geographically diverse locations. In one urgent case, trial activation, patient consent, screening, and treatment were achieved in 5 business days. In total, 91.7% of patients consented to trial. The average timeline from activation to consent was 4.5 days (range 0 - 24 days), with half of patients consenting within 1 business day. 45.5% of patients who consented to trial received the study drug within 1 day of consent; 2 patients dosed on day of consent. Conclusions: Over a 3-month period, on average, TIME Trial sites were activated in 9.4 days (compared to the 20+ week industry-wide average), and patient consent was completed in 4.5 days. Rapid JIT activations through the TIME program provide significant improvements in trial enrollment timelines and increase access to therapies nationwide. JIT activations may be especially useful for rural, underserved communities, as sites can enroll diverse patient populations and help address the equity gap in clinical trials across ethnic groups.[Table: see text]
Oliver Gillie: medical journalist and vitamin D campaigner
Authors: John Illman
Journal: BMJ (2021)

Oliver Gillie helped to transform medical journalism and public perception of medicine—with assistance from one of the most controversial surgical operations in history. In 1967, a year before Gillie started his journalistic career on Science Journal (which later became part of New Scientist ), Christiaan Barnard performed the world’s first human-to-human heart transplantation. Heart transplants are now routine, but many people then thought they could not or should not be done. Barnard became the most celebrated name in medicine since Hippocrates. The operation was as big a media story as the first steps on the moon in 1969.

Medicine had been publicly silent and privately critical, with debate confined mainly to journals, medical common rooms, meetings, and the royal colleges. In Hearts Exposed—Transplants and the Media in 1960s Britain , Ayesha Nathoo, wrote: “The intense public interest in heart transplantation significantly contributed to pulling medical discussion out of its traditional esoteric and exclusive confines.”

Gillie saw his role in this revolution as a shift from the “simple popularisation of expert knowledge” to a more analytical stance. After only four years in journalism he moved to the rarified atmosphere of the Sunday Times , which exposed the thalidomide scandal. Thalidomide was to medical journalism what Watergate was to politics. Medicine and big pharma had never before been exposed to such scrutiny.

Gillie was not part of the thalidomide team, but …