tbuckley/cabot-search huggingface dataset:
Recurrence rates in cervical cancer patients treated with abdominal versus minimally invasive radical hysterectomy: A multi-institutional analysis of 700 cases.
Authors: Shitanshu Uppal, Paola Gehrig, Monica Hagan Vetter, Brittany Anne Davidson, Brittany F Lees, Laurie Leigh Brunette, Katherine Tucker, Koji Matsuo, Kristin Leigh Bixel, Allison Stuart Staley, Walter H. Gotlieb, Robert W. Holloway, Kathleen N. Moore, Stephen L. Rose
Journal: Journal of Clinical Oncology (2019)

5504 Background: Compare outcomes between open and minimally invasive radical hysterectomy. Methods: Retrospective multi-institutional review of patients undergoing radical hysterectomy for stage IA1, IA2 and IB1 squamous, adeno- or adeno-squamous carcinoma between 01/01/2010 - 12/31/2017. Results: From 704 cases that met the inclusion criteria, 185 (26.3%) underwent open and 519 (73.7%) underwent minimally invasive surgery (MIS). Women treated with open surgery were older, had larger tumors on preoperative assessment as well as on final pathology assessment, had higher proportion of patients with IB1 stage and adjuvant therapy. Patients undergoing open surgery had longer median follow-up compared to MIS (44 vs. 30.3 months, p &lt; 0.001). The two groups were similar in regard to race distribution, body mass index, comorbidities and preoperative histology. There were 13/185 (7%) recurrences and 10/185 (5.4%) deaths in the open compared to 42/519 (8.1%) recurrences and 26/519 (5%) deaths in MIS (p = n.s for both). However, on multivariate analysis, after controlling for race, comorbidities, preoperative tumor size, histology, grade and smoking status, MIS had higher odds of recurrence (OR 2.24, 95% CI 1.04 - 4.87, p = 0.04). On a second model, in addition to prior mentioned factors, we included lymphovascular space invasion, receipt of adjuvant therapy and vaginal margin status. Undergoing MIS remained associated with higher odds of recurrence (OR 2.37, 95% CI 1.1 - 5.1, p = 0.031). On sub-group analysis of cases with preoperative tumor size less than equal to 2 cm, there were 5/121 (4.1%) recurrence in open and 25/415 (6%) recurrences in MIS group (p = 0.34). Multivariate analysis did not show a higher rate of recurrence in MIS arm in this subgroup. In 26 cases of MIS where no vaginal manipulator was used, no recurrences were noted. In comparison 19/270 (7%) recurrences were noted in intra-uterine manipulator (V-care/Zumi/Rumi) and 22/210 (11%) in vaginal manipulators (EEA sizer/Colpo Probe) groups (p = 0.119). Conclusions: In this large retrospective analysis, patients undergoing MIS for early stage cervical cancer had higher odds of recurrence. In patients with 2 cm or less tumor on preoperative assessment, recurrence rates were similar between the two groups. Role of manipulator in increasing recurrence should be further studied in this patient population.
Barriers to Ensuring Access to Affordable Prescription Drugs
Authors: Michelle M. Mello
Journal: The Annual Review of Pharmacology and Toxicology (2019)

High and rising prescription drug costs have become a preoccupying policy problem in the United States. Notwithstanding broad, bipartisan interest in finding effective policy solutions, several aspects of the drug affordability problem make it an uncommonly difficult one to solve. This article reviews the moral, market, and political factors contributing to the difficulty. Among the moral problems is lack of agreement about how to weigh the fundamental tradeoff involved in regulating drug prices-affordability versus incentives for innovation-and about what constitutes a fair price. Market-related factors include the lack of price transparency and a myriad of perverse incentives in the system through which prescription drugs are supplied to patients. Finally, current policy choices are constrained by past political compromises, and an atmosphere of scandal focusing on egregious instances of price gouging has made rational deliberation about fixes to deeper problems in the system difficult.
Docetaxel, trastuzumab, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2-positive breast cancer: Results from the Swedish PREDIX HER2 trial identifying a new potential de-escalation standard?
Authors: Jonas C. S. Bergh, Anne Andersson, Judith Bjohle, Ana Bosch, Lena Carlsson, Ann Charlotte Dreifaldt, Zakaria Einbeigi, Hanna Fredholm, Erika Isaksson-Friman, Theodoros Foukakis, Ellinor Elinder, Mats Hellstrom, Hemming Johansson, Tobias Lekberg, Henrik Lindman, Claudia Maes, Yvonne Brandberg, Thomas Hatschek
Journal: Journal of Clinical Oncology (2019)

501 Background: Neoadjuvant therapy produces high rates of pathological complete response (pCR) and is the standard of care in HER2 positive breast cancer; however, the optimal treatment regimen remains to be established. Methods: In this randomized phase II study patients ≥18 years with HER2 positive breast cancer &gt; 20mm or verified lymph node metastases were randomized to 6 courses of docetaxel, trastuzumab and pertuzumab (DTP, group A) or trastuzumab emtansine (T-DM1, group B), q 21 days. The protocol allowed switch to the competing treatment upon lack of response or drug-related severe toxicity. Patients received postoperative epirubicin+cyclophosphamide, trastuzumab for a total of one year and endocrine therapy. Accrual was completed in October 2018 after randomization of 202 patients, data on pCR were available for 190 at the time for this abstract submission. Median age, 52 years (26-74), menopausal status, histological type and grade were well balanced between the treatment groups. 62.6% of the tumors were hormone receptor (HR) positive. Results: Primary endpoint was pathological objective response. 190 patients completed the protocol-specified preoperative treatment. pCR was achieved in 45.3% of patients, 46.4% in patients treated with DTP and 44.1% with T-DM1 (chi-sq., p = 0.75). In HR-positive tumors, pCR was obtained in 35.3% of patients, 35.9% in group A vs. 34.6% in group B (p = 0.87); in HR-negative tumors, the overall pCR rate was 62.0%, 66.7% in group A vs. 57.9% in group B (p = 0.45). Severe (grade 3/4) toxicity was reported at 68 occasions related to DTP, compared with 16 related to T-DM1, 26 vs. 3 caused by febrile neutropenia. Significantly better quality of life was reported by patients treated with T-DM1. Conclusions: Our data on TDM-1 demonstrates similar efficacy and less toxicity, in particular for patients with HER2 and HR positive cancers, being a potential new standard for neoadjuvant therapy. Clinical trial information: NCT02568839.
Immune-mediated colitis after resumption of immune checkpoint inhibitor therapy.
Authors: Hamzah Abu-Sbeih, Faisal Ali, Abdul Rafeh Naqash, Dwight Hall Owen, Sandip H. Patel, Gregory Alan Otterson, Kari Lynn Kendra, Biagio Ricciuti, Rita Chiari, Andrea De Giglio, Joseph Sleiman, Pauline Funchain, Wills Beatriz, Jiajia Zhang, Jarushka Naidoo, Jessica Philpott, Jianjun Gao, Sumit Kumar Subudhi, Yinghong Wang
Journal: Journal of Clinical Oncology (2019)

2577 Background: Immune checkpoint inhibitor (ICI) therapy is often suspended because of immune-mediated diarrhea and colitis (IMDC). We examined the recurrence rate and risk factors for IMDC after ICI resumption. Methods: This retrospective multicenter study examined patients who resumed ICI therapy after improvement of IMDC between 1/2010 and 11/2018. Univariate and multivariate logistic regression analyses assessed the association of clinical covariates and IMDC recurrence. Results: Of the 167 patients in our analysis, 32 resumed an anti-CTLA-4 agent and 135 an anti-PD-1/L1 agent. The median duration from IMDC to restart of ICI treatment was 49 days (IQR, 23-136). IMDC recurred in 57 (34%) patients overall (44% of those resuming an anti–CTLA-4 and 32% resuming an anti–PD-1/L1 agent); 47 of these patients (82%) required immunosuppressive therapy for recurrent IMDC (Table). The median duration from ICI resumption to IMDC recurrence was 53 days (IQR 22-138). On multivariate logistic regression, patients who received anti-PD-1/L1 therapy at initial IMDC had a higher risk of IMDC recurrence (odds ratio [OR], 3.45, 95%CI, 1.59-7.69; P&lt;0.01). Risk of IMDC recurrence was higher for patients who required immunosuppression for initial IMDC (OR, 3.22; 95%CI, 1.08-9.62; P=0.02) or had longer duration of IMDC symptoms in the initial episode (OR, 1.01; 95%CI, 1.00-1.03; P=0.03). Risk of IMDC recurrence was lower for those who resumed anti–PD-1/L1 therapy than for those who resumed anti–CTLA-4 therapy (OR, 0.30; 95%CI, 0.11-0.81; P=0.02). Conclusions: One-third of patients who resumed ICI treatment after IMDC experienced recurrent IMDC. IMDC recurrence was less frequent after resumption of anti–PD-1/L1 than after anti–CTLA-4. Characteristics of recurrent IMDC based on resumed ICI therapy. [Table: see text]
Potential length of stay reduction with outpatient management of low risk febrile neutropenia in a regional cancer centre.
Authors: Mike Nguyen, Tate Jacobson, Babak Tamjid, Javier Torres, Arvind Sahu, Alysson Wann
Journal: Journal of Clinical Oncology (2019)

e18000 Background: Febrile neutropenia is a serious complication of chemotherapy. The Multinational Association for Supportive Care in Cancer (MASCC) risk index score can reliably identify patients with febrile neutropenia at low risk of serious complications. Outpatient management programs utilising protocol based risk stratification, daily ambulatory nursing visits, telephone follow up and early outpatient review have been successfully piloted in other Australian cancer treatment centres. Methods: We performed a retrospective review of medical records for all patients admitted at our institution with febrile neutropenia between January 1 2016 and December 31 2018. We collected information regarding patient characteristics, cancer diagnosis and treatment, determined the MASCC risk index score, and if low risk, we determined the potential eligibility for outpatient care and potential reduction in length of stay. Results: A total of 98 hospital admissions with febrile neutropenia were analysed. Of these, 66 were determined to have a MASCC low risk index score. 58 patients met the eligibility criteria for outpatient management. The median age was 67 years. 71% were female. The most common tumour type was breast cancer. 52% were treated with palliative intent. The median length of stay was 3 days. The median potential reduction in length of stay for each admission was 2 days. The total potential reduction in length of stay was 198 days. No admission resulted in serious complications indicating the safety of outpatient care. Conclusions: Febrile neutropenia is a common complication of chemotherapy and a leading cause of hospital admission. This review demonstrates a significant number of hospital admission days can be avoided with outpatient care. We intend to conduct a prospective pilot study at our centre to institute an outpatient febrile neutropenia program for such low risk groups with potential reduction in hospital bed length of stay. This has significant implications on health resource usage, service provision planning and patient quality of life.
Intra and perinodular CT delta radiomic features associated with early response to predict overall survival (OS) in immunotherapy-treated non-small cell lung cancer (NSCLC): A multisite multi-agent study.
Authors: Prateek Prasanna, Mohammadhadi Khorrami, Amit Gupta, Pradnya Dinkar Patil, Monica Khunger, Priya Velu, Kaustav Bera, Mehdi Alilou, Vamsidhar Velcheti, Anant Madabhushi
Journal: Journal of Clinical Oncology (2019)

2588 Background: None of the current biomarkers for predicting response to checkpoint inhibitors (ICIT) for advanced NSCLC are associated with long-term benefits, such as improved OS. In this multi-agent (nivolumab, pembrolizumab, or atezolizumab) multi-site study (Cleveland Clinic, Univ. of Pennsylvania), we demonstrate that changes in computer-extracted textural patterns, from within and 30mm outside the nodules, between baseline and post-treatment CT following ICIT correlate with RECIST-derived responses, and are prognostic of OS. Methods: CT scans from 139 NSCLC patients both pre-, and post 2-3 cycles of ICIT were acquired from 2 sites. Patients with objective response/stable disease per RECIST v1.1 were defined as ‘responders’, and those with progressive disease were ‘non-responders’. The cohort was divided into a discovery (D1 = 50) and two validation sets (D2 = 62, D3 = 27). 454 intranodular texture (IT) features, and 7426 perinodular features (PT) were extracted from the temporalscans, Relative differences were computed to yield a set of ‘delta-radiomic’ descriptors. In D1, 8 features that evolved the most between baseline and post-treatment CT, and performed the best in identifying responders, were determined. These were then used with a Linear Discriminant Analysis classifier to identify the responders from the non-responders. We then computed a radiomic risk score (RRS) system and tested its prognostic ability in assessing differences in OS. Results: A combination of 5 IT, 3 PT delta radiomic features yielded an AUC of 0.88 ± 0.08 in D1 and a corresponding AUC = 0.85 and 0.81 in D2 and D3, respectively. Multivariate survival metrics are shown in Table. Conclusions: Delta-radiomic features, both from inside and outside the nodules, could be used to identify patients likely to derive clinical benefit from ICIT (eg: OS) beyond anatomic response. [Table: see text]
Real-world effectiveness of palbociclib in combination with an aromatase inhibitor as first-line therapy in metastatic breast cancer.
Authors: Xianchen Liu, Jack Mardekian, Lynn McRoy
Journal: Journal of Clinical Oncology (2019)

e12541 Background: Palbociclib in combination with an aromatase inhibitor (AI) was approved as initial endocrine therapy for patients with HR+/HER2– metastatic/advanced breast cancer (mBC) in February 2015. Evidence of real world outcomes for the combination to date has been limited by small sample size and short follow-up. This study describes patient characteristics and effectiveness of palbociclib + AI as first-line therapy in a large cohort of mBC patients in US clinical practice. Methods: Utilizing Flatiron Health’s longitudinal database, a retrospective cohort study was conducted to evaluate patients with HR+/HER2– mBC who started palbociclib + AI as first-line therapy between February 3, 2015 and August, 31, 2018. Patients were evaluated retrospectively from start of palbociclib + AI therapy on or after February 3, 2015 to November 30, 2018, death, or last visit in the database, whichever came first. Real-world progression free survival (rwPFS) was defined as months from start of palbociclib + AI therapy to death or disease progression based on clinical assessment or evidence by radiographic scan/tissue biopsy. Kaplan-Meier methods were used to estimate survival proportions in overall survival (OS) and rwPFS. Results: Of 878 who met the criteria, 66.9% were white, mean age was 65.2 years, 50.8% had visceral disease (liver and/or lung involvement), and 94% were treated in community practice. Patients were followed up to 46 months. Median rwPFS was 21.9 months (95% CI = 20.1 – 28.2). At 3 years of follow-up, OS rate was 91.9%. For additional outcomes, see Table. Conclusions: These findings from the largest cohort yet evaluated for real world effectiveness confirm the effectiveness of palbociclib + AI in routine clinical practice as a standard of care for first line treatment of HR+/HER2- mBC. [Table: see text]
Prognostic value of sequential <sup>18</sup>F-FDG + Na<sup>18</sup>F PET/CT (NaF+FDG PET) in metastatic genitourinary (GU) cancer patients (pts) treated with cabozantinib/nivolumab +/- ipilimumab (CaboNivoIpi).
Authors: Nicholas Peter Verdini, Ilhan Lim, Esther Mena, Liza Lindenberg, Amir Mortazavi, Sumanta K. Pal, Primo Lara, Katherine Graap, Marissa Mallek, Corrine Keen, Ryan Thompson, Christian Mayfield, Corinne Turrell, Jacqueline Cadena, Biren Saraiya, Ray L Lilly, Michael V. Knopp, Chadwick Wright, Seth M. Steinberg, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2019)

4544 Background: NaF+FDG PET imaging are used to assess soft tissue and bone metastases. The prognostic value of NaF+FDG PET in GU cancer pts was assessed as a secondary endpoint within a phase I trial of combination CaboNivoIpi. Methods: NaF+FDG PET scans were collected at baseline and cycle (C)3 day (D)1 for 50pts. Up to 50 lesions/patient were analyzed at baseline, up to 10 lesions/organ in case of extensive disease. Lesion number and whole-body metabolic tumor volume (wMTV) were recorded at baseline, C3D1 and percent change for FDG and NaF scans. Whole-body total lesion glycolysis (wTLG) and its percent change was obtained for FDG scans. Parameters were evaluated with respect to OS using Kaplan-Meier and log-rank, with quartiles, then refined to show strongest distinction, adjusting p-values to account for this exploration. Parameters with strongest OS association were also analyzed for associations with OS in urothelial carcinoma (UC) pts. Results: 50 pts, (UC (n = 20); others (renal cell, prostate, urachal/adenocarcinoma, germ cell, penile, bladder squamous cell (n = 2-7 each)). Median (m) overall survival (OS) was 23.9 months (mo) (95% CI: 13.7mo – NE) with 29.7mo m potential follow up and mOS of 24.7mo (95% CI: 13.7mo-NE) for UC. For FDG in all pts, wMTV: baseline ≤ vs &gt; 51.6, mOS (NR vs 10mo, p = .0006), C3D1 ≤ vs &gt; 85 mOS (25.9mo vs 5.1mo, p = .0001), percent change (0/increase vs decrease, mOS 14mo vs 25.9mo, p = .015); wTLG: baseline ≤ vs &gt; 178, mOS (NR vs 11.5mo, p = .011), C3D1 ≤ vs &gt; 300, mOS (25.9mo vs 8.3mo, p &lt; .0001), percent change decrease vs increase, mOS (25.9mo vs 14.0mo, p = .016); and lesion number: baseline ≤ vs &gt; 13, mOS (25.9mo vs 9.9mo, p = .0090), C3D1 ≤ vs &gt; 13 mOS (25.9mo vs 9.9mo, p &lt; .0001) significantly predicted OS. In UC pts, wMTV percent change (0/increase vs decrease, mOS 14mo vs. 25.9mo, p = .057), wTLG percent change decrease vs increase, mOS (NR vs 8.4mo, p = .0015), and lesion number C3D1 ≤ vs &gt; 13 mOS (25.9mo vs 2.8mo, p = .022) significantly predicted OS. NaF parameters failed to do so. Conclusions: FDG wMTV and wTLG at baseline, C3D1, and percent change and lesion number at baseline and C3D1, predicted OS in GU cancer pts on CaboNivoIpi. Clinical trial information: NCT02496208.
Therapeutic and prognostic impacts of specific gene alterations for squamous cell lung cancer: A result of nationwide genome screening in Japan (LC-SCRUM-Japan).
Authors: Terufumi Kato, Shingo Matsumoto, Shigeki Umemura, Kiyotaka Yoh, Kazumi Nishino, Haruko Daga, Yukari Tsubata, Noriyuki Ebi, Shingo Miyamoto, Masato Shingyoji, Shigeki Hashimoto, Taku Nakagawa, Satoshi Hara, Koichi Goto
Journal: Journal of Clinical Oncology (2019)

9060 Background: Various gene alterations occur during the development of squamous cell lung cancer (SqLC), but specific gene alterations for SqLC and their clinical significance remain unknown. Methods: In a nationwide genome screening project (LC-SCRUM-Japan), we have prospectively analyzed lung cancer patients for genetic alterations using a next-generation sequencing (NGS) system, Oncomine Comprehensive Assay, and have established a large-scale clinico-genomic database. Results: Since February 2013 to December 2018, a total of 6692 lung cancer patients (686 SqLCs, 5360 non-squamous non-small cell lung cancers [Non-sq] and 646 small cell lung cancers [SCLCs]) had been enrolled in the LC-SCRUM-Japan. The success rate of the NGS assay was 91%. Of 639 SqLCs analyzed, 274 (48%) had potentially targetable gene alterations, including 77 NFE2L2 (encoding NRF2) mut, 50 PIK3CA mut, 46 FGFR1 amp, 40 EGFRmut/amp, 36 PTEN mut, 23 KRAS mut, 6 AKT1 mut, 6 MET ex14skip, 5 ALK fusions, 2 FGFR3 fusions. Among the alterations detected, NFE2L2 mut and FGFR1 amp were significantly frequent in SqLC than Non-sq or SCLC (NFE2L2, 12.1% vs. 1.0% vs. 1.3%; p &lt; 0.001, and FGFR1, 7.2% vs. 1.1% vs. 3.4%; p &lt; 0.001). In advanced SqLC patients who received platinum-containing chemotherapies, the median progression-free survival (mPFS) was significantly shorter in NFE2L2-mutated patients (NRF2-type) than NFE2L2/FGFR1-negative patients (nonNF-type) (3.8 [95%CI, 2.9-5.1] vs. 4.5 [95%CI, 3.8-5.4] months, p = 0.03), and similarly, the mPFS of FGFR1-amplified patients (FGFR1-type) (3.5 months [95%CI, 1.5-4.9]) tended to be shorter than that of nonNF-type (p = 0.07), although the response rates were equivalent among the three types. NRF2-type also showed shorter overall survival (OS) than nonNF-type (median OS, 10.4 [95%CI, 6.9-22.3] vs. 16.6 [95%CI, 13.6-21.7] months, p = 0.10). Therapeutic efficacy of nivolumab or pembrolizumab was not different among these types in the current follow-up data. Conclusions: Our large scale genome screening identified specific gene alterations for SqLC and the alterations were associated with a less efficacy of chemotherapy and worse prognosis, suggesting the need for the development of genotype-directed therapeutic strategy for SqLC patients.
Leveraging a conversational agent to support adherence to oral anticancer agents: A usability study.
Authors: Bethany Mooney Berges, Christine Cambareri, Samuel U Takvorian, Mike Serpa, Lawrence N. Shulman, Justin E. Bekelman, Katharine A. Rendle, Jesse Argon, Roy Rosin
Journal: Journal of Clinical Oncology (2019)

6534 Background: Identifying effective, scalable strategies to ensure patient adherence to oral anticancer agents (OACAs) is a major challenge. Previous studies have shown widely variable rates of adherence, and suboptimal adherence is associated with decreased effectiveness and higher costs. A small but growing literature supports digital health behavioral interventions across a variety of chronic illnesses, including in cancer. In particular, conversational agents—or technologies that mimic human conversation using text or spoken language—have shown early promise in supporting behavior change, but have yet to be rigorously tested in the context of OACAs. Methods: A rapid cycle prototyping approach led to the development of ‘Penny’ – a bidirectional, conversational agent that engages patients via text messaging, and leverages natural language processing and machine learning to learn from clinical interactions. Core functionalities include: (1) real-time dosing instructions, (2) motivational reminders, and (3) symptom monitoring with self-management support. We conducted a four-month usability study between December 24, 2017 and May 1, 2018 in a large academic cancer center. At monthly intervals for the first 12 weeks of follow-up, research staff conducted qualitative interviews with participants to evaluate usability and acceptance. Results: 11 patients with gastrointestinal neuroendocrine cancer on capecitabine and temozolomide were approached regarding the study. Of these, 10 agreed to participate (ages 45 to 71). Overall, participant satisfaction was high with a Net Promoter Score of 100. Reliability of Penny’s algorithmic branching to provide accurate dosing information and symptom triage was also high: symptoms were accurately graded 100% of the time, and there was appropriate self-management advice or provider triage 100% of the time. Average daily adherence (based on self-report) was 98%. Participants reported that 3 emergency room visits were avoided during the study period. Conclusions: In preliminary testing, a mobile phone-based conversational agent was a usable and acceptable means of supporting OACA adherence. Expanded study testing patient safety and efficacy is underway.