tbuckley/cabot-search huggingface dataset:
Community oncologists perceptions and readiness to implement Medicare Access and CHIP Reauthorization Act (MACRA).
Authors: Bela Bapat, Yolaine Smith, Andrew Klink, Chadi Nabhan, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2019)

e18374 Background: The Medicare Access and CHIP Reauthorization Act (MACRA) was introduced in 2015 with the intention of transforming healthcare administration to improve the quality of care and lower its cost. Understanding challenges facing physicians in how to implement MACRA and recognizing their perceptions regarding these challenges are critical steps to the success of this program and future transformation efforts. Methods: In this study, US oncologists attending live meetings were surveyed on their perceptions of MACRA. Data were collected in 2 time periods: period 1 spanned Nov 2016 to Jun 2017 and period 2 spanned Sep 2018 to Nov 2018. Each physician attended a live meeting in each period. Data were collected in period 1 using audience response system technology and web-based surveys; period 2 data were collected using web-based surveys only. We aimed to compare responses between periods 1 and 2 to assess whether perceptions and challenges changed. Results: There were 97 community oncologists and/or hematologists who responded to both periods. Of the responding physicians, 31.2% were participating in the Oncology Care Model program. A greater proportion of physicians expressed some level of confidence in executing MACRA requirements and achieving financial success in period 2 compared to period 1 (74.2% vs 52.4%; P&lt; 0.01). Additionally, more physicians in period 2 reported having the resources and staffing needed to manage changes required by MACRA (24.7% vs 11.4%; P= 0.02). Strategies in place to improve on compliance with MACRA did not significantly change between both periods (34.2% vs. 28.9%; P = 0.45). Confidence that MACRA would improve patient outcomes in the long-term was expressed by 33.0% in period 2, which was significantly higher than in period 1 (17.6%; P= 0.02). However, most physicians in period 1 were not confident that MACRA would reduce cost of care (89.6%), but this improved to 61.9% in period 2 ( P&lt; 0.01). Conclusions: Over time, oncologists seem more confident about their practices’ readiness for implementing MACRA. However, they remain skeptical of MACRA’s likelihood of improving quality or cost of cancer care and appear to need better strategies to assure sustainability.
Randomized phase III trial of 68Ga-PSMA-11 PET/CT molecular imaging for prostate cancer salvage radiotherapy planning [PSMA-SRT].
Authors: Jeremie Calais, Johannes Czernin, Wolfgang P Fendler, David Elashoff, Nicholas George Nickols
Journal: Journal of Clinical Oncology (2019)

TPS136 Background: Salvage radiotherapy (SRT) for prostate cancer (PCa) biochemical recurrence (BCR) after radical prostatectomy (RP) is commonly initiated in patients with PSA &lt; 1 ng/mL, a threshold at which standard-of-care imaging is insensitive for detecting recurrence. The purpose of this randomized phase 3 trial is to evaluate the success rate of SRT for PCa BCR after RP with and without planning based on 68Ga-PSMA-11 PET/CT (PSMA). Here we present the study protocol. Methods: This is an interventional phase 3 randomized prospective open label clinical trial with parallel assignment designed for superiority. Patients who are planned to undergo SRT for PCa BCR with PSA &gt; 0.1 ng/ml are eligible. The choice of treating the prostate bed with/without pelvic lymph nodes, with/without androgen deprivation therapy, is left to the discretion of the treating radiation oncologist (RO). RO may or may not change the RT plan depending on the PSMA findings. Any other imaging is allowed for SRT planning if done per routine care. The primary endpoint is the success rate of SRT measured as biochemical progression-free survival (PFS) after initiation of SRT. Biochemical progression is defined by PSA≥0.2 ng/mL and rising. Based on literature data we hypothesized that 1) the incorporation of PSMA to SRT planning will improve 5-year PFS by 20%, 2) the 5-year PFS will be 60% in standard Arm 1 and 80% in interventional Arm 2, and 3) 13% of subjects randomized to Arm 2 will have extra-pelvic metastasis detected by PSMA and will not be included in analysis of the primary endpoint. We will randomize 193 patients (1:1.13 ratio) to proceed with standard SRT (n = 90) or undergo PSMA scan (free of charge for patients) prior SRT planning (n = 103). Patients will be followed for 5 years after the date of initiation of SRT. Discussion: Main pitfalls in study design include 1) drop-out of patients randomized to the control arm and 2) potential FDA approval of PSMA PET imaging probes in the near future (no randomization to standard arm would be then acceptable). This is the first prospective randomized phase 3 trial designed to determine whether PET/CT can improve outcome of SRT in patients with BCR. Clinical trial information: NCT03582774.
Palbociclib (P) in patients (pts) with non-small cell lung cancer (NSCLC) with <i>CDKN2A</i> alterations: Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) Study.
Authors: Eugene R Ahn, Pam K. Mangat, Elizabeth Garrett-Mayer, Susan Halabi, Elie G. Dib, Daniel Ernest Haggstrom, Kathryn B. Alguire, Ricardo H. Alvarez, Carmen Julia Calfa, Timothy Lewis Cannon, Pamela A. Crilley, Anu G. Gaba, Alissa S. Marr, Ashish Sangal, Ramya Thota, Kaitlyn R. Antonelli, Samiha Islam, Andrew Lawrence Rygiel, Suanna S. Bruinooge, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2019)

9041 Background: TAPUR is a phase II basket study evaluating anti-tumor activity of commercially available targeted agents in pts with advanced cancers with genomic alterations. Results in a cohort of NSCLC pts with CDKN2A loss or mutation treated with P are reported. Methods: Eligible pts had advanced NSCLC, no standard treatment options, measurable disease, ECOG PS 0-2 and adequate organ function. Genomic testing was performed using commercially available tests. Pts matched to P had NSCLC with CDKN2A loss or mutation and no RB mutations. A Simon two-stage design was used to test a null rate of 15% vs. 35% (power = 0.85; α = 0.10). If ≥2 of 10 pts in stage 1 have disease control (DC) (objective response (OR) or stable disease at 16 weeks (wks) (SD16+)), an additional 18 pts are enrolled. If ≥7 of 28 pts have DC, the drug is considered worthy of further study. Secondary endpoints are progression-free survival (PFS), overall survival (OS) and safety. Results: Twenty-nine pts were enrolled from January 2017 to June 2018; 1 pt was unevaluable for response but is included in safety analyses. Pts received P at 125 mg orally once daily for 21 days, followed by 7 days off. Demographics and outcomes are summarized in Table (N = 28). One PR and 6 SD16+ were observed for a DC rate of 29% (90% CI, 15% to 37%). 10 pts had at least one grade 3 or 4 AE or SAE at least possibly related to P with the most common being cytopenias. Other grade 3-4 AEs or SAEs at least possibly related to P included fatigue, anorexia, febrile neutropenia, myocardial infarction, sepsis, vomiting, and hypophosphatemia. Conclusions: Monotherapy with P demonstrated evidence of anti-tumor activity in heavily pre-treated NSCLC pts with CDKN2A loss or mutation . Additional study is warranted to confirm the efficacy of P in pts with NSCLC with CDKN2A loss or mutation. Clinical trial information: NCT02693535. [Table: see text]
Molecular profiling using the 92-gene assay for tumor classification of brain metastases.
Authors: Andrew Jacob Brenner, Raul Collazo, Catherine A. Schnabel, F Anthony Greco
Journal: Journal of Clinical Oncology (2019)

e13583 Background: Nearly 200,000 patients are diagnosed with brain metastases in the US annually. Advances in targeted therapies make definitive diagnosis of the primary tumor type important but can be challenging in many patients. The 92-gene assay is a validated gene expression classifier of 50 tumor types/subtypes for patients with uncertain diagnoses. Results from a clinical series of brain biopsies and potential impact on treatment were evaluated. Methods: An IRB-approved, de-identified database of clinical and molecular information from biopsies (N = 24,486) submitted for testing with the 92-gene assay (CancerTYPE ID, Biotheranostics, Inc.) as part of routine care were reviewed. Descriptive analysis included patient demographics and molecular diagnoses. Results: Analysis included 464 brain biopsies. A molecular diagnosis was provided in 433 (93.3%) tested ( &lt; 5% assay failure rate) with 24 different tumor types. Six primary tumor types made up the majority (67.4%) with almost one-third of the molecular predictions being Lung (31.2%), followed by Neuroendocrine (NET) (9.9%), Sarcoma (7.9%), Skin (6.4%), Gastroesophageal (6.2%), and Urinary bladder (5.8%). All of these 6 tumor types, for which activity in the CNS has been documented, have immune checkpoint inhibitors or other targeted therapies approved in selected cases by the US Federal Drug Administration (FDA) (Table). Conclusions: Molecular classification of brain metastases can identify distinct tumor types for which there are FDA approved targeted medications. Improving diagnostic precision with the 92-gene assay helps identify a subset of therapy-responsive metastatic brain tumors, thus improving therapy and possibly providing better outcomes and survival. [Table: see text]
Data from an integrated cancer prevention center screening for multiple cancer types.
Authors: Ezra Bernstein, Ofer Isakov, Lior Galazan, Ari Leshno, Meital Shaked, Eliezer Liberman, Eyal Gur, Hanoch Elran, Miri Sror, Amira Harlap-Gat, Shlomi Kleinman, Moran Steiner, Galit Aviram, Arye Blachar, Ada Kessler, Orit Golan, Shiran Shapira, Ravit Geva, Ido Wolf, Nadir Arber
Journal: Journal of Clinical Oncology (2019)

e13069 Background: Cancer is the second leading cause of death globally, and was responsible for ~9.6 million deaths in 2018. Importantly, between 30–50% of cancers can be prevented by avoiding risk factors and implementing existing evidence-based prevention strategies. Methods: We present the results of 15758 adults who came to our clinic between 2006 and 2018. Patients were counseled on reducing risk factors and screened for early detection of 11 of the most common cancer types. Patients were examined by specialists in internal medicine, surgery, plastic surgery, OBGYN, urology, oncology, oral surgery, gastroenterology, and others. Women underwent vaginal US, pap smear, mammography (40yr) and US/MRI of the breast with a clinical indication. Men underwent PSA/free PSA ( &gt; 40yr). LDCT for moderate smokers. Colonoscopy was recommended to all subjects ( &gt; 40yr). Results: A total of 7900 (50.1%) men and 7857 women (49.9%) mean age 46.9±11.3 years were screened. A total of 418 (2.7%) malignant lesions were detected in patients who had been screened, 245 (1.6%) of which were detected through our screening: skin 66 (0.4%), prostate 30 (0.2%), thyroid 28 (0.2%), breast 28 (0.2%), colorectal 19 (0.1%), urinary 13 (0.08%), lung 11 (0.07%), cervical 11 (0.07%), other/unknown 9 (0.06%), hematologic 8 (0.05%), ovarian 5 (0.03%), uterine 5 (0.03%), pancreas 3 (0.02%), testicular 3 (0.02%), oropharyngeal 2 (0.01%), hepatobiliary 2 (0.01%), stomach 1 (0.01%), larynx 1 (0.01%). A total of 17 (0.1%) malignant lesions were missed: breast 3 (0.02%), colorectal 3 (0.02%), skin 2 (0.01%), thyroid 2 (0.01%), hematologic 2 (0.01%), pancreas 2 (0.01%), kidney 1 (0.01%), lung 1 (0.01%), brain 1 (0.01%). A total of 147 (0.9%) malignant lesions developed &gt; 1year after a visit. Only forty-nine of the cancer patients (12.5%) died after 18.9±17.8 months at a mean age of 66.5±12.2 years. Significantly, better than the expected cancer mortality in general. First-degree family member with cancer (HR = 1.46) and advanced age (HR = 21.8) was associated with increased cancer risk (P &lt; 0.05). Conclusions: One stop shop cancer screening, in the setting of a multidisciplinary outpatient clinic is feasible, can detect cancer at an early stage, and can significantly improve survival.
Phase II study of apatinib combined with vinorelbine in second-line treatment failure non-driver gene mutation advanced non-small cell lung cancer (NCT03652857).
Authors: Yongchang Zhang, Fang Wu, Yi Xiong, Xiangyu Zhang, Nong Yang
Journal: Journal of Clinical Oncology (2019)

e20669 Background: There is currently no standard treatment strategy for non-driver gene mutation advanced non-small cell lung cancer (NSCLC) patients experiencing progression after two or more lines of chemotherapy. Our study assessed the efficacy and safety of apatinib combined with vinorelbine in non-driver gene advanced NSCLC patients for whom at least two lines of prior chemotherapy had failed. Methods: This is a Phase II, single arm clinical trial. 30 advanced NSCLC patients who had two or more prior lines of chemotherapy had failed enrolled in this study. All the patients received treatment of apatinib 500mg, po qd plus vinorelbine 60mg/m2 po qweek. The primary endpoint was overall response rate (ORR). Secondary endpoints were overall (OS), progression-free survival (PFS), disease control rate (DCR) and safety. Results: Between January 2016 and November 2018, 30 patients were enrolled. 25 patients finished all the treatment. 5 patients discontinued the treatment for adverse events. The ORR of all the patients was 36.3 %( 11/30). The DCR of all the patients was 76.3 %( 23/30). The median PFS of all the patients was 4.5months (95% CI 2.4-6.6m). The median OS of all the patients was 10months (3.8m-16.2m). The most common grade 3 to 4 adverse events were non-hematologic including hand-foot syndrome. Moreover, medicine reduction seem not be an important role in disease prognosis. Conclusions: These data show that apatinib combined with vinorelbine can be a good choose with an acceptable safety profile in non-driver gene mutation advanced NSCLC patients refractory to two or more lines of prior chemotherapy. Clinical trial information: NCT03652857.
Real-world evidence regarding the efficacy and toxicity of neoadjuvant trastuzumab and pertuzumab in the management of HER2-positive early-breast cancer.
Authors: Benjamin James Hall, Ajay Ashok Bhojwani, Helen Innes, Eliyaz Ahmed, Joanne Cliff, Zaf Malik, Julie Elizabeth O'Hagan, Shaun Tolan, Allison Hall, Khizar Hayat, Douglas Errington, Farida Alam, Nicky Thorp, Helen Flint, Andrea Law, Helen Wong, Susan O'Reilly, Richard Jackson, Silvia Cicconi, Carlo Palmieri
Journal: Journal of Clinical Oncology (2019)

e12108 Background: Neoadjuvant (NA) HER2 blockade with trastuzumab (T) and pertuzumab (P) results in pathological complete response (pCR) rates of 39% to 62%. Diarrhoea is reported in up to 73% of cases. No real-world studies have explored the efficacy and toxicity of this treatment. This study aimed to determine the efficacy and toxicity of NA T-P and CT within a routine NHS clinical practice in the UK. Methods: HER2+ BC patients given NA T-P (accessed via the Cancer Drug Fund) between Oct2016-Jan 2018 at Clatterbridge Cancer Centre NHS Foundation Trust were retrospectively identified. Clinico-pathological information, treatment data, nurse led toxicity and echocardiography were reviewed. Data lock: 30 th January 2019. Final pathological response data is presented. Results: 78 female patients were identified with a median age of 50 years (IQR: 44.4-60.2). Diagnosis: median tumour size 30mm (IQR 23.0-47.5mm), 62% (48/78) LN+ &amp; 71% ER+. CT regimens: 81% (63/78) given FEC-DHP; of these 19 (30%) switched to weekly paclitaxel (wP) or nab-paclitaxel; 5% (4/78) AC/EC-DHP; 9% (8/78) TCHP of which 1 (13%) switched to wP. All patients underwent definitive surgery: 50% (39/78) mastectomy &amp; 50% (39/78) WLE. 44% (35/78) axillary node clearance (ANC) &amp; 56% (43/78) sentinel node biopsy (4 prior to NA therapy). 91% (32/35) undergoing ANC were LN+ at diagnosis, of which 66% (21/32) were LN- at surgery. pCR rate (ypT0/is, N0) was 47% (37/78), pCR by HR: ER+ 42% (23/55) &amp; ER- 61% (14/23). pCR for 20 cases switched to wP was 60% (12/20). 6% (5/78) achieved pCR in the breast alone (in these LN status ITCx1, micrometsx3 &amp; macrometsx1). Median size of the 46% (36/78) with residual breast tumour was 14.5mm (1-65mm). Outcome: Median follow up 68 weeks with one local and one distant recurrence occurring but no deaths. Toxicity: Ejection fraction did not decline beyond 10% of baseline in any patients. Diarrhoea occurred in 74% of cases, and CTCAE grade 3-4 toxicity occurring in &gt;2% of patients: diarrhoea, fatigue, and infection. Conclusions: This data confirms 1) the real world efficacy of NA T-P 2) a significant number of LN+ patients become LN- and measures to avoid ANC are needed 3) switching to NA wP is not uncommon and may be associated with a higher pCR 4) diarrhoea rates reflect the literature and measures to mitigate it are needed. Updated outcomes will be presented.
Impact of HER2 aberrations on EGFR-TKI treatment outcomes in lung tumors harboring EGFR mutations: A HER2-CS STUDY subset analysis.
Authors: Hiroe Kayatani, Keisuke Aoe, Kadoaki Ohashi, Hiroshige Yoshioka, Akihiro Bessho, Nobuhisa Ishikawa, Masahiro Yamasaki, Toshiyuki Kozuki, Nobukazu Fujimoto, Yutaka Ueda, Syuuji Bandoh, Isao Murakami, Hirohisa Ichikawa, Tetsuya Kubota, Keisuke Sugimoto, Nagio Takigawa, Takashi Sumikawa, Katsuyuki Kiura
Journal: Journal of Clinical Oncology (2019)

9056 Background: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are a key treatment for EGFR-mutated non-small-cell lung carcinoma (NSCLC). To date, a biomarker to predict whether NSCLC will exhibit a short- or long-term response to first- or second-generation EGFR-TKIs has not been established for clinical use. Human epidermal growth factor receptor-2 (HER2) aberrations are mechanisms for acquired resistance to EGFR-TKIs; however, their impact on EGFR-TKI therapy outcomes in EGFR-mutant NSCLC has not yet been systematically evaluated. Methods: Patients with advanced NSCLC were prospectively registered from more than 35 institutes (HER2-CS STUDY UMIN 000017003). EGFR mutations or anaplastic lymphoma kinase gene translocations were assessed at each institution using a commercially approved test. HER2 protein expression levels were determined by immunohistochemistry (IHC) using the Ventana I-VIEW PATHWAY anti-HER-2/neu (4B5). The IHC status scoring system applied to gastric cancer was used. Results: Of 1,126 screened patients with NSCLC, 354 (31.8%) had EGFR-mutated tumors, and the HER2 protein statuses were as follows: IHC0 (n = 71, 26%), IHC1+ (n = 148, 53%), IHC2+ (n = 51, 18%), and IHC3+ (n = 7, 3%). The patients’ demographics were almost identical in those with lung tumors harboring EGFR mutations and HER2-IHC2+/3+ (group P) or EGFR mutations and HER2-IHC0/1 (group N). The EGFR-TKI response rates were not different between these groups (Table). However, group P showed significantly shorter time to EGFR-TKI treatment failure than group N (median 19.1 vs. 13.3 months; log rank p = 0.038). Conclusions: These data from a large prospective cohort show that HER2 protein expression in EGFR-mutant NSCLC may have a negative impact on the effect of EGFR-TKIs. A clinical trial of EGFR/HER2-TKIs (e.g., afatinib) is warranted for this population. [Table: see text]
Differential vaginal wall dosing in high-dose rate brachytherapy for endometrial cancer: The potential for superior coverage of at-risk areas while preserving organs at risk—An analysis of simulated data.
Authors: Dhiraj Sinha, Kellie Alleyne-Mike, Sherisse De_four, Naveen Ratan, Shashidhar Ramesh
Journal: Journal of Clinical Oncology (2019)

e17121 Background: The treatment of curable endometrial cancer (EC)involves surgery with adjuvant radiotherapy. Histology of EC is a major determining factor for intracavitary brachytherapy (ICRT) treatment volume in early stage EC. Many guidelines recommend ICRT treatment of an extended volume up to the whole length of the vaginal stump (VS) for cases of high risk histologies (HRH) wherein a differential dosing of proximal and distal VS has the potential to achieve targeted therapeutic doses to at risk areas without compromise to critical structures.We present a simulated novel way to treat the VS by ICRT in cases of EC with HRH. Analysis of the simulated and approved plans allow us to compare the doses to organs at risk (OAR’s). Methods: Seventy-five cases from July 2017-August 2018 were reviewed and twenty-five (25) met the criteria for inclusion in this study. All these cases received External Beam Radiation Therapy (EBRT) dose of 50.4Gy/28. The ICRT simulation CT data-set was subsequently used to generate the study plan which was then compared to the actual treatment plan. In order to treat the whole VS but spare OARs a club-shaped design was proposed. This technique involved treating the upper 1/3 with a prescription point at 0.5cm lateral to the applicator surface and the lower 2/3 with a prescription point at the applicator surface. The length of the VS was defined from the tip of the applicator to 2cm superior to the introitus. The D2cc values for the contoured bladder and rectum were extracted from the treatment plan and used along with the D2cc values from the EBRT treatment to calculate OAR EQD2. QUANTEC Constraints used were (ICRU 83): EQD2 bladder: 90Gy; EQD2 rectum: 75Gy. Once calculated, the results were analyzed and the percent deviation between the proposed plan and the constraints as well as the approved plan were determined. Results: Twelve (12) of twenty-five (25) cases were HRH cases. The club-shaped design to treat the whole VS didn't further compromise the OAR (EQD2: 22% below constraints) or the rectum (EQD2: 1% below constraints). There was only a 2% difference between the final constraints in both treatment techniques. Conclusions: This technique to treat the full VS length can be used without adversely affecting OAR toxicities with superior coverage to at risk areas while maintaining dose constraints to OAR. Results, however, are limited by the small sample size.