Cancer Network Clinical Practice Guidelines Research Articles

Changes in Length and Complexity of Clinical Practice Guidelines in Oncology, 1996-2019

This cross-sectional study calculates the increase in clinical cancer knowledge represented in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines from 1996 to 2019.

Oral management strategies for radiotherapy of head and neck cancer.

SummaryRadiotherapy, often with concomitant chemotherapy, has a significant role in the management of head and neck cancer, however, radiotherapy induces adverse events include oral mucositis, hyposalivation, loss of taste, dental caries, osteoradionecrosis, and trismus, all of which have an impact on patients’ quality of life. Therefore, it is necessary to implement oral management strategies prior to the initiation of radiotherapy in patients with head and neck cancer. Since 2014, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) have enumerated the “Principles of Dental Evaluation and Management (DENT-A)” in the section on head and neck cancers, however, oral management was not explained in detail. Oral management has not been achieved a consensus protocol. The aim of this literature is to show that oral management strategy include removal infected teeth before the start of radiotherapy to prevent osteoradionecrosis, oral care for preventing severe oral mucositis to support patient complete radiotherapy during radiotherapy, and prevent of dental caries followed by osteoradionecrosis after radiotherapy.

Patient burden and clinical advances associated with postapproval monotherapy cancer drug trials: a retrospective cohort study

ObjectivesAfter regulatory approval, drug companies, public funding agencies and academic researchers often pursue trials aimed at extending the uses of a new drug by testing it in new non-approved indications....

Sentinel Lymph Nodes and Precision Surgery in Gynecologic Cancer.

Besides histologic features, the presence of nodal metastasis is the most crucial prognostic factor for recurrence and survival for patients with gynecologic cancer. Conventionally, lymphadenectomy has been performed routinely to assess lymphatic metastasis. However, lymphadenectomy may be unnecessary in early-stage gynecologic cancer, because the percentage of patients with lymph node involvement is very low. The recent use of sentinel lymph node mapping has provided high feasibility, safety, and accuracy in the assessment of nodal metastasis. The National Comprehensive Cancer Network Clinical Practice Guidelines have incorporated the sentinel lymph node for nodal evaluation in vulvar, endometrial, and cervical cancers.

Clinicopathological analysis of early-stage breast cancer patients that meet indications for BRCA1/2 genetic testing.

ObjectiveTo investigate the clinicopathological characteristics and prognostic factors of early-stage breast cancer patients with indications for breast cancer susceptibility genes 1/2 (BRCA1/2) genetic testing in China. MethodsBased on the indication criteria for BRCA genetic testing specified in the National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology, genetic/familial high-risk assessment: Breast and ovarian (Version 2. 2019), a retrospective analysis was performed on patients with early-stage invasive breast cancer treated at Breast Disease Center, Peking University First Hospital between January 2008 and December 2016. Clinicopathological characteristics of all patients were analyzed, and prognoses were calculated using the Kaplan-Meier method and a Cox proportionate hazards model. ResultsA total of 906 early-stage breast cancer patients who had indications for BRCA genetic testing and had complete clinicopathological data and follow-up information were included in the study group, accounting for 34.7% of all breast cancer patients treated in Breast Disease Center, Peking University First Hospital during the study period. Compared with breast cancer patients without indications for BRCA genetic testing, the overall survival (OS) and disease-free survival (DFS) of patients with indications were not significantly different. In the study group, patients with premenopausal status, high T stage, lymph node positive, estrogen receptor (ER) negative, Ki-67>20% and presence of a vascular tumor thrombus had worse prognosis. There were more family histories of gastrointestinal cancer in patients with related indications than in patients without such indications. ConclusionsSingle-center data showed that more than 30% of patients with early-stage breast cancer had indications for BRCA genetic testing. There was no prognostic difference in patients with or without indications for BRCA genetic testing. Premenopausal status, high T stage, lymph node positive, ER negative, Ki-67>20%, and presence of a vascular tumor thrombus were associated with poor prognosis.

Geriatric Assessment Identifies Impairments in Younger Candidates for Allogeneic Hematopoietic Stem Cell Transplantation

Introduction: Geriatric assessment (GA) is a multidimensional evaluation of patient health and function that may detect impairments not identified as part of routine care, predict treatment-related morbidity and mortality, and inform treatment plans. Given evidence of these benefits, the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend GA for older candidates of hematopoietic stem cell transplantation (HCT). However, both older and younger HCT candidates will often receive multiple rounds of chemotherapy before HCT, leading to functional impairments in all age groups. Furthermore, HCT patients often experience a significant gap between when they are first evaluated and actually proceed to transplant (e.g., while a donor search is conducted), creating an opportunity to identify impairments and optimize function prior to transplant. Methods: To address this opportunity, we created a clinical pre-HCT optimization program (C-POP) to evaluate physical function, cognitive function, nutritional status, and mental health in all adults who were deemed potential candidates for allogeneic HCT by a HCT physician. We applied this standard of care program to all adult candidates for HCT, regardless of age, with the goal of identifying functional impairments and then referring patients to services to optimize those impairments prior to HCT. We defined impairments using validated measures and compared results to established norms or scoring, controlling for age and gender where appropriate (e.g., the cut-off for six-minute walk distance was adjusted for age, gender, height, and weight, while the cut-off for falls was any fall regardless of characteristics). Patients with impairments were referred to the appropriate supportive care (e.g., physical function impairment -> referral to physical therapy). Results were prospectively analyzed at new patient evaluation (NPE), which was the first time the patient met a HCT physician and sign-off, which occurred within a week before starting transplant. While the program is ongoing, we present here the results of patients evaluated between October 16th, 2017 and July 1st, 2019. Patients are divided into three pre-specified age groups: <40 years old, 40-59 years old, and >=60 years old, with results compared using a chi-squared test. Results: We evaluated 115 patients: 21 (18%) <40 years, 40 (35%) 40-59 years, and 54 (47%) >=60 years). There were no differences between the age groups in other demographics (gender, race, and ethnicity). At NPE, 93 (81%) met criteria for at least 1 impairment in physical function, cognitive function, nutritional status, or mental health; 62 (54%) met criteria for impairments in 2 or more areas. Surprisingly, patients <40 years were more likely to screen positive for physical function (20/21, 95%) than patients 40-59 years (26/40, 65%) and patients >=60 years (36/54, 67%) (p=0.03). Of those 115 patients, 52 (45%) proceeded to HCT, including 12 (57%) <40 years, 18 (45%) 40-59 years, and 22 (41%) >=60 years (p=0.75); of those patients who have not proceeded to HCT, 40 (35%) will never proceed to HCT (e.g., deemed not a candidate after functional evaluation or died of disease prior to HCT) while 23 (20%) are still awaiting HCT (e.g., donor search ongoing). Patients who proceeded to HCT were less likely to have mental health impairments (2/52, 4% vs. 9/40, 23%, p=0.006). Of the 52 who were seen at new patient evaluation and proceeded to transplant, 40 (77%) were seen at sign off. Of those who had impairments at NPE, 12/23 (52%) improved their physical function to normal limits, 4/9 (44%) improved their cognitive function, and 9/13 (69%) improved their nutritional status by the time of sign-off (of those who were seen at sign-off, none had mental health impairments at NPE). Discussion: These results demonstrate that younger as well as older candidates for HCT exhibit a high degree of functional impairment. However, this impairment could be amenable to improvement prior to HCT. These findings support application of GA to all HCT candidates regardless of age. We will investigate the effect of referred interventions (e.g., physical therapy, seeing a dietician) in improving functional impairments in future studies, as well as look at the effect of these findings on HCT outcomes. Disclosures Wiggins: Incyte, Inc.: Speakers Bureau. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Rizzieri:Millennium: Speakers Bureau; Novartis: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Incyte: Consultancy, Speakers Bureau; TEVA: Consultancy; Spectrum: Consultancy; Kite Pharma: Consultancy; Gilead Sciences: Consultancy, Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Jazz Pharmaceuticals: Speakers Bureau. Horwitz:Abbvie Inc: Membership on an entity's Board of Directors or advisory committees. Sung:Novartis: Research Funding; Merck: Research Funding; Seres: Research Funding.

Economic Burden of Neurologic Toxicities Associated with Treating Relapsed Refractory Diffuse Large B-Cell Lymphoma in the United States

Introduction: Chimeric antigen receptor T (CAR-T) cell therapies targeting CD19 antigen can yield durable remissions in relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). Yet the use of CAR-T can be limited by potentially severe toxicities, principally cytokine release syndrome (CRS) and neurologic toxicities. Management of neurologic toxicities requires vigilant monitoring, supportive treatment and resource allocation. We found no studies reporting healthcare costs associated with treatment-related neurologic adverse events (NEAEs) in r/r DLBCL patients. The objective of this study was to develop an evidence-based list of r/r DLBCL treatment-related NEAEs and to estimate the healthcare costs associated with these NEAEs in a real-world setting. Methods: Grade 3 or higher NEAEs that occurred in ≥2% of patients were identified by reviewing U.S. drug prescribing information (PI), European Medicines Agency summaries of product characteristics, and published clinical trials for treatments of r/r DLBCL. Then, adult patients ≥18 years old with r/r DLBCL were identified from a U.S. administrative claims database containing de-identified claims for over 150 million people across over 11 years. Patients were included if they had: 1) evidence of treatment beyond first-line (2L+) during the identification period (07/01/14 - 12/31/18); and 2) ≥1 inpatient or ≥2 outpatient claims for DLBCL (ICD-9-CM codes: 200.7X; ICD-10-CM codes: C83.3X) during the study period (01/01/14 - 12/31/18) with ≥1 having occurred prior to or on the date when the 2L+ treatment was received. 2L+ treatments were selected based on National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines and clinical expert input. To maximize the identification of patients treated with CAR-T, treatments were categorized hierarchically into 4 groups: CAR-T therapy (axicabtagene ciloleucel, or tisagenlecleucel), high-intensity cytotoxic therapy (carboplatin, cisplatin, cyclophosphamide, or ifosfamide), low-intensity cytotoxic therapy (bendamustine, lenalidomide, or gemcitabine), and targeted monotherapy (rituximab, ibrutinib, or brentuximab vedotin). The index date was defined as the start date of the 2L+ treatment. Patients in the cytotoxic and targeted therapy groups were also required to have evidence of an earlier line of cytotoxic or targeted therapy. All patients were required to have ≥6-months continuous enrollment before the index date. The outcomes of interest were the rates of NEAEs and total healthcare costs for patients with and without NEAEs during the 30-day post index period. Costs were inflated to 2018 US dollars. Descriptive statistics were reported. Results: Twenty-three NEAEs were identified based on the review: 17 for CAR-T, 10 for conventional immunochemotherapy regimens, and 4 for both. In the claims database, a total of 349 adult patients with r/r DLBCL were identified, including 27 CAR-T therapy, 262 high-intensity cytotoxic therapy, 50 low-intensity cytotoxic therapy, and 10 targeted therapy users. Mean (median, SD) patient age was 72.3 (73; 10.3) years, with 47.9% being female and 83.4% having Medicare insurance. Patients were mainly from the South (44.1%) and the Midwest (31.5%). The mean (SD) Charlson comorbidity index was 4.4 (3.6) and mean (SD) number of chronic conditions was 7.3 (2.2). Forty-five (12.9%) patients had ≥1 NEAE at some point during the 30-day post-index period. Of these, 14 (31.1%) were CAR-T users. Eleven (40.7%) of the CAR-T users had encephalopathy. Mean total healthcare costs were $99,611 higher for patients with NEAEs [mean (SD): $153,435 (227,771)] than those without any NEAEs [$53,824 (96,170)]. Among patients with NEAEs, 72% of the healthcare costs were accrued in the inpatient setting. Among patients without NEAEs, 63% of the healthcare costs were for outpatient medical services. The trend of higher costs in patients with NEAEs was consistent across treatment groups. Conclusion: This is the first study of the economic burden of NEAEs associated with treating r/r DLBCL in a real-world setting with data that reflects the current range of treatment options. Patients with r/r DLBCL who have NEAEs incur substantially higher costs than those without such events. In this analysis, CAR-T is overrepresented for NEAEs, although the sample size is small. We intend to repeat the analysis when more claims data becomes available in the near future. Disclosures Broder: Partnership for Health Analytic Research (PHAR), LLC: Other: I am an employee of the Partnership for Health Analytic Research (PHAR), LLC, which was paid by Novartis to conduct the research described in this abstract.. Ma:Novartis Pharmaceuticals Corporation: Employment. Yan:Partnership for Health Analytic Research (PHAR), LLC: Other: T. Yan is an employee of Partnership for Health Analytic Research (PHAR), LLC, a health services research company paid to conduct this research.. Chang:Partnership for Health Analytic Research (PHAR), LLC: Other: E. Chang is an employee of Partnership for Health Analytic Research (PHAR), LLC, a health services research company paid to conduct this research.. Eldjerou:Novartis Pharmaceuticals Corporation: Employment. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Kuzan:Novartis Pharmaceuticals Corporation: Employment. Zhang:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership.

The Clinical Application of Oncomine Myeloid Next Generation Sequencing (NGS): Comparison of Cytogenetics and NGS in Patients with Suspected Myelodysplastic Syndrome

Background: A common referral to hematology is for patients with suspected myelodysplastic syndrome (MDS) or cytopenias of undetermined origin. We recently implemented a Next Generation Sequencing (NGS) panel which covers a wide spectrum of genes related to the major myeloid disorders, including DNA based gene sequencing and RNA based gene fusion analysis, as a tier one clinical diagnostic test (Levy et al. Eur. J. Haematol 2019). We compared the diagnostic and prognostic information derived from conventional cytogenetics and NGS testing as well as the clinical impact on management in this patient group. Methods: We identified all new cases with suspected MDS or cytopenias of undetermined origin referred between January 2018 to February 2019 that had both NGS and cytogenetic testing at London Health Sciences Centre, a tertiary care centre servicing a population of approximately 2.5 million in Southwestern Ontario, Canada. From the retrospective review of electronic medical record, patient demographics, diagnosis and management were ascertained. Diagnosis was based on the 2016 WHO classification and the ICD-10.Previously reported definitions for ICUS, IDUS, CHIP, and CCUSwere also adopted (Bejar et al. Leukemia 2017). Patients not meeting these criteria were defined as either cytopenia not yet determined (NYD) or secondary to other systemic disease. The impact of NGS and cytogenetics results on diagnosis, prognosis, and management of each disease were assessed by referring to the latest National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology. Either a bone marrow (BM) or peripheral blood (PB) sample from each patient was assessed by the Oncomine Myeloid NGS panel (Thermo-Fisher, MA, USA), which examines DNA sequence variants in 40 genes (17 full genes and 23 hotspot genes) along with an RNA-based panel of 29 fusion driver genes and their over 600 fusion partners. Patients' BM samples were also tested by the conventional cytogenetic G-banding method. Results: Of the 1100 samples assessed by NGS, 178 met the study inclusion criteria. Overall, 120 (67.4%) patients had both cytogenetics and NGS performed on their BM samples. Of those 120 patients, 41 (34.2%) had DNA mutations, 17 (14.2%) had cytogenetic abnormalities, 22 (18.3%) had both molecular and cytogenetic findings, and 40 (33.3%) had neither abnormality identified. NGS Information contributed in diagnosing 13 (10.8%) patients, while cytogenetics in 6 (5%) patients. In addition, of 38 patients who were diagnosed as MDS with good/intermediate risk cytogenetics, 24 (63.2%) harbored poor prognostic risk mutations as detected by NGS (Table), influencing the management of disease. Additionally, 22 (12.4%) of all patients had NGS testing using PB and cytogenetics using BM samples, and of these 13 (52.2%) patients had NGS abnormalities. Finally, 36 (20.2%) of all patients had only NGS testing by PB samples. Of those, 12 (33.3%) were found to harbor at least one gene mutation including ASXL1, TP53, ZRSR2, and STAG1 suggesting poor prognostic significance for diagnoses of MDS, or JAK2, SF3B1 which could support a disease specific diagnosis. Conclusion: NGS had enhanced diagnostic capabilities including classification of newly described entities such as ICUS or CCUS and more importantly yielded additional prognostic information compared to cytogenetics alone for this patient population. Cytogenetic findings were mainly aneuploidy or deletions, either clinically evident constitutional abnormalities such as Trisomy 21 and +X in Klinefelter syndrome, or loss of Y chromosome in a small proportion of cells and thus of questionable clinical significance. Based on this information consideration should be given to using the NGS panel as the primary molecular diagnostic and prognostic tool with karyotyping being reserved for subsets of patients being assessed for suspected MDS or cytopenias of undetermined origin. Disclosures Hsia: Amgen: Honoraria; Jansen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees.

206P - Population-based validation of the risk stratification among prostate cancer patients

BackgroundTo compare discriminant ability of risk stratifications for prostate cancer in three authoritative guidelines: National Comprehensive Cancer Network clinical practice guideline (NCCN-g), American Urological Association / American Society for Therapeutic Radiology and Oncology/ Society of Urologic Oncology Guideline(AUA-g) and European Association of Urology- European association of nuclear medicine- European Society for Radiotherapy and Oncology- European Society of Urogenital Radiology- International Society of Geriatric Oncology guideline(EAU-g). Methods511916 patients with one primary prostate cancer diagnosed between 2004 and 2016 were identified using the Surveillance, Epidemiology, and End Results (SEER, submitted in) database of the National Cancer Institute. Patients were excluded from analysis if < 18 years of age, not adenocarcinoma, diagnosed at autopsy or death certificate only, with an unknown follow-up, incomplete clinical and demographic information, leaving 287333 patients in this cohort. Patients were categorized as different risk stratifications by three latest guidelines (NCCN-g, AUA-g and EAU-g) respectively. Follow-up endpoint was prostate cancer specific mortality (PCSM), cutoff date was December 31, 2016. Kaplan–Meier analysis, multivariable Cox regression and area under the receiver operating characteristics (ROC) curve (AUC) analyses were performed. ResultsThe 287333 patients are all from 2004 to 2015. Median follow-up was 69 months (IQR: 39-104). For the three risk stratification modalities, all 6 risk groups in NCCN-g, 5 risk groups in AUA-g and 5 risk groups in EAU-g independently predicted PCSM. NCCN-g yielded 3.1-fold HR differences between low risk group and intermediate risk group, 14.8-fold HR differences between low risk group and high risk group, 33.0-fold HR differences between low risk group and very high risk group, 56.2-fold HR differences between low risk group and regional group, and 148.9-fold HR differences between low risk group and metastatic group. AUC is 0.8332, 0.8309 and 0.7868 in NCCN-g, AUA-g and EAU-g. ConclusionsThis large population-based analysis confirms the better discriminant properties of the risk stratification method in NCCN guideline. Legal entity responsible for the studyPeking University First Hospital radiation oncology department. FundingHas not received any funding. DisclosureThe author has declared no conflicts of interest.

P1.03 Case Series of Double Mutations in Patients with Lung Adenocarcinoma

The introduction of targeted therapies has increased the survival time in a subset of patients with NSCLC. The National Comprehensive Cancer Network (NCCN) clinical practice guidelines in oncology recommend measuring the local EGFR gene mutations of NSCLC patients before treatment. Sensitivity to EGFR TKIs in patients with double or multiple mutations is not well described. In the literature there are few reported cases of double mutations. We present a series of six cases of Lung Adenocarcinoma with double mutations found between 2006 and 2017 in a hospital in Northern MX. 450 patients with Lung cancer were evaluated from 2006 to 2017. DNA extraction is performed using a commercial extraction kit, the process is performed by real-time PCR on an automated platform in a closed circuit with a commercial panel. The DNA quantification quality control process is analyzed, validating with positive and negative controls, then analysis of the 29 known mutations of EGFR gene exons 18, 19, 20, 21. This study includes 450 patients, 141 (31.33%) patients had EGFR mutations, of which six (4.25%) had double exons EGFR mutations. Of the six cases with double mutations, male to female ratio was 1:1. The histological patterns reported in the double mutations were: 3 (50%) cases with acinar pattern, 2 (33.33%) with micropapillary pattern, and 1 (16.66%) solid pattern. The median age of the six patients is 54 years (range 38-78).Tabled 1First MutationSecond MutationHistological patternAge of patientCase #1L858RL861QAcinar52Case #2L858RExon 19 deletionMicropapillary55Case #3Exon 19 deletionL861QMicropapillary38Case #4Exon 19 deletionT790MSolid53Case #5Exon 19 deletionL861QAcinar78Case #6Exon 19 deletionL858RAcinar55 Open table in a new tab EGFR co-mutation had a significantly lower mean progression-free survival than those with a single mutation (5.7 months vs. 12.3 months). The response rate to TKI was significantly worse in those with co-mutation compared to those without co-mutation (38% vs 89%). There are few studies evaluating all the characteristics of cases with double mutations, such as histological pattern and the mutations of EGFR gene exons. Further research on double mutations is suggested because of the impact on treatment and prognosis of the patient.

P1.11-08 Are Risk Prediction Models Superior Over Standard Criteria for Lung Cancer Screening in Europe? Macroscale Simulation on Large Polish Cohort

Inauguration of the national lung cancer screening programme in Poland is to take place in 2019. Yet, issues such as optimal selection criteria remain unresolved. A computational macroscale simulation of lung cancer risk prediction models’ implementation and comparison in a large lung cancer screening cohort of 5,534 individuals from a single, experienced European center was performed. A total of 5,534 healthy volunteers (aged 50-79, smoking history ≥30 pack-years) were enrolled in the Moltest Bis Programme (Moltest) between 2016 and 2017. Inclusion criteria were based on the Lung Cancer Screening National Comprehensive Cancer Network Clinical Practice Guidelines. Each participant underwent a low-dose computed chest tomography scan and selected participants underwent a further, diagnostic work-up. A computational macroscale simulation of Tammemagi PLCOm2012, Liverpool Lung Project (LLP) and Bach risk models’ implementation was applied. Jupyter notebook v.1.0 scientific environment was used to calculate lung cancer probability of all Moltest participants. Patients i) with 6-year lung cancer probability ≥1.3% were considered as high risk in PLCOm2012 model, ii) in LLP model with 5-year lung cancer probability ≥5.0%, and iii) in Bach model with 1-year lung cancer probability ≥2.0%. Such selected patients were eligible for the inclusion to the simulated lung cancer screening programme. Boolean functions were created and data frames containing patients’ epidemiological characteristics were joined using Pandas Python Library v.0.23 for Python v.3.7. In a computational macroscale simulation 3,897 (70.4%), 3,118 (56.3%) and 925 (16.7%) out of 5,534 Moltest participants met the threshold criteria of lung cancer probability in PLCOm2012, LLP and Bach models, respectively. With 199 (3.6%) Moltest individuals initially referred for diagnostic work-up in the programme, lung cancer was confirmed in 105 (1.9%) cases. Contrarily, among high-risk individuals selected based on PLCOm2012, LLP and Bach models, respectively, 103 (2.6%), 56 (1.8%) and 24 (2.6%) constituted the lung cancer cases primarily detected in the Moltest programme. Thus, in PLCOm2012, LLP and Bach models the proportions of screen-detected lung cancer cases were 98.1%, 53.3% and 22.9%, respectively. Risk prediction models provide a vast disparity in selecting lung cancer high-risk individuals. Lung cancer screening enrollment based on Tammemagi’s PLCOm2012 risk prediction model is superior over LLP, Bach models and standard selection criteria based on age and pack-years.

MS07.04 Stage I (Resectable) NSCLC: Surgery

MS07.04 Stage I (Resectable) NSCLC: Surgery

Financial conflicts of interest among the National Comprehensive Cancer Network (NCCN) Clinical Practice Guideline (CPG) Panelists in 2019.

15 Background: CPG are evidence-based guidelines, which serve as a standard of care in practice, quality improvement, and reimbursement. The extent of financial conflicts of Interest (FCOI) in NCCN guidelines has not been recently evaluated. Our study evaluated the extent of FCOI in the NCCN CPG among the 10 most common malignancies in the US. Methods: We examined the latest 2019 version of the NCCN CPG for the 10 most common cancers by incidence in the US. Using disclosure lists, we catalogued the FCOIs for the panelists under various categories outlined in the CPG. We also tabulated the companies/institutions involved in each disclosure. An “episode” describes 1 instance of participation of a panelist in 1 company in 1 category of each guideline. “Affiliation” describes a commercial, industry, or institute affiliation reported by a panelist in each episode. Results: Of the 491 panelists on the CPG, 483 (98.3%) completed FCOI disclosures. 224 (46.38%) reported at least 1 FCOI. A total of 1,103 episodes were disclosed with an average of 4.9 episodes per panelist with FCOI. Being a part of scientific advisory boards, consultant, or expert witness was the most common FCOI category (19.9%). A total of 191 companies were associated with 1,103 episodes of FCOI. The top companies were Bristol Myers Squibb, Merck, Genentech and AstraZeneca. Among the top 10 cancers, the prevalence of FCOI were lung (56%), bladder (52%), pancreatic (52%), non-Hodgkin lymphoma (50%), kidney (49%), colorectal (43%), breast (42%), melanoma (40%), prostate (38%), and uterine (32%). Among the panelists with FCOI, 26%, 17%, and 57% reported 1, 2, and &gt; 3 episodes, respectively. There were 127 episodes among the CPG chairs/vice chairs who reported FCOI (mean 6.4). The chairs/vice chairs of uterine, pancreatic, melanoma, and prostate cancer CPG did not have any FCOI. Conclusions: FCOI are very prevalent among the top 10 NCCN CPG panelists. In almost half of the CPG, the majority of the panelists had at least 1 FCOI. Over half of the CPG chairs/vice chairs reported multiple FCOI. Further studies are necessary to determine the impact of these FCOI.

Validity of Using Cancer Registry Data in Comparative Effectiveness Research Involving Radiation Therapy

Randomized clinical trials represent the gold standard in comparative effectiveness research, yet many clinical scenarios lack randomized data therefore turning researchers to analyses using other data sources. A large body of comparative effectiveness research uses cancer registry data to compare survival among different treatments. However, the non-randomized nature of these analyses is subject to potential confounding and selection bias. The purpose of this study was to determine whether comparative effectiveness analyses using cancer registry data from the National Cancer Database (NCDB) produces results concordant with randomized trials in radiation oncology. We identified randomized clinical trials involving radiation therapy referenced in the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for central nervous system, head and neck, breast, lung, esophageal, gastric, pancreas, rectal, anal, bladder, prostate, lymphoma, uterine, and cervical cancers. We included only randomized trials with treatment arms identifiable within NCDB. For each trial we extracted patients from NCDB matching the eligibility criteria of the randomized trial whenever possible. For each trial we used three Cox regression models to determine hazard ratios (HRs) for overall survival: univariable, multivariable, and propensity score adjusted models. Multivariable analyses controlled for potential confounders including demographic, comorbidity, clinical, treatment and tumor-related variables. Each NCDB survival analysis was defined as discordant if the HR for the NCDB analysis fell outside the 95% confidence interval of the corresponding randomized trial. Separately, we also assessed for disagreement with statistical significance, with p<0.05 for NCDB and p>0.05 for the clinical trial (or vice versa) defined as discordant. Thirty-two randomized trials met inclusion criteria. NCDB analyses produced hazard ratios for survival discordant with randomized trials in 16 (50%) univariable analyses, 10 (31%) multivariable analyses, and 12 (37%) propensity score analyses. NCDB analyses produced p-values discordant with randomized trials with 26 (81%) univariable analyses, 22 (69%) multivariable analyses, and 20 (62%) propensity score analyses. We did not identify any clinical trial characteristics specifically associated with discordance between NCDB analyses and randomized trials including disease site, severity of cancer, or era of trial. Comparative effectiveness research involving radiation therapy using NCDB frequently produces results discordant to randomized data. Multivariable or propensity score analysis modestly improves concordance between NCDB and clinical trials. Caution should be used when interpreting comparative effective research with cancer registry data.

Advances in the Study of the Effects of Video-assisted Thoracoscopic Segmentectomy on Pulmonary Function

2018年美国国立综合癌症网络关于非小细胞肺癌（non-small cell lung cancer, NSCLC）指南指出，对于早期NSCLC，解剖性肺叶切除为首选方案。随着电视胸腔镜技术的发展，以胸腔镜为代表的胸外科微创手术在临床得到了广泛应用。胸腔镜肺段切除术已经成为早期NSCLC的治疗方案之一。临床研究发现相较于肺叶切除，亚肺叶切除在早期NSCLC治疗中也可取得相似的结果并保留更多的肺功能，但肺段切除术后患者肺功能的改变尚存争议。本文将重点对胸腔镜肺段切除术后患者肺功能改变的研究进展做一综述。

The relationship of plasma fibrinogen with clinicopathological stages and tumor markers in patients with non-small cell lung cancer.

Numerous studies have shown that the blood of cancer patients are generally in hypercoagulable statement. The aim of the present research is to study the relationships of plasma fibrinogen (Fbg) levels with clinicopathological stages (CS) and tumor markers of non-small cell lung cancer (NSCLC).Baseline information, plasma Fbg levels, CS, and expression level of tumor markers were collected from medical records retrospectively. Unitary linear regression was used to analyze the relationships between continuous variables and Fbg, and multiple linear regression was used to analyze the relationships between categorical variables and Fbg. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (Version 4) for NSCLC were adopted to evaluate CS.A total of 652 NSCLC patients were included. Compared with the females, male patients had higher mean plasma Fbg levels (P < .001). The later the N stages (P = .002), M stages (P = .002), and CS (P = .001) were, the higher the average plasma Fbg levels were. The levels of squamous cell carcinoma antigen (P = .001), carbohydrate antigen 125 (P = .041), and neuron-specific enolase (P < .001) were positively correlated with plasma Fbg concentration. The plasma level of Fbg in lung adenocarcinoma patients (P < .001) was the lowest, while that of lung squamous cell carcinoma patients (P < .001) was the highest in NSCLC patients.The plasma Fbg concentration is related to gender, CS, and tumor markers in patients with NSCLC.

Abstract P3-03-14: Clinical utility of one-step nucleic acid amplification (OSNA) in axillary surgery after neoadjuvant chemotherapy (NAC)

Abstract Introduction NAC has been used for downsizing of the tumour in breast and axilla to allow more conservative surgery. In the NAC setting, intraoperative assessment of sentinel lymph node(s) (SLN) is still considered necessary1. Current awareness of the prognostic value for axillary nodal down-staging has renewed interest in analysis of SLN post-NAC. In this study we want to examine the clinical utility of OSNA (based on CK19 mRNA detection) as a method of intra-operative analysis of SLN to assist real-time decision-making for axillary surgery post-NAC in early breast cancer (EBC). Methods Retrospective analysis of prospective data on 399 consecutive patients with EBC who received NAC followed by breast surgery with SLN biopsy (408 axillae) and assessment by OSNA, from September 2011 to January 2018 at the Royal Marsden Hospital (UK). OSNA readouts from the Sysmex RD-100i were collected separate to and blinded from clinico-pathological data. A negative or benign pre-treatment axillary ultrasound scan or indeterminate ultrasound with negative or benign axillary cytology/histology prior to NAC was considered cN0. Univariate analysis (significance at p&amp;lt;0.05) was used to identify risk of recurrence. Patients had a median (mean) follow up of 32.5 (36) months. Results The median age at diagnosis was 49 years, median BMI 26, 41 EBC (10%) were screen-detected, 292 (72%) were grade 3 and the most frequent phenotype was receptor triple negative (n=132, 32%). Of 408 axillae, 248 (60%) were initially cN0, of which 113 (46%) had a pathological complete response (pCR) in the breast. SLN in 54 (22%) cN0 patients were positive on OSNA, of which only 6 (9%) had further involved axillary nodes all 6 of which were ER+ Her2-. The remaining 160 (40%) axillae were cN1 of which 87 (54%) had conversion to ypN0 including 55 (34%) with both ypT0ypN0. Axillary lymphadenectomy (AL) was performed in 79 (19%) patients overall, of which n=22 (28%) were cN0 and 57 (72%) were cN1. Of these, 30 (53%) of the cN1 and 6 of 22 (45%) of cN0 had at least 1 additional positive AL node. Overall 59 (14.4%) patients relapsed. A significantly worse rate of relapse was observed in cN1 compared to cN0 patients (37/159 (23.3%) versus 22/244 (9%), p&amp;lt;0.001). Combined pCR of both breast and axilla (in cN1, n=54) was associated with a significantly reduced risk of relapse and death (p&amp;lt;0.001) compared to those without pCR of either breast or axilla (n=62). Of the latter 18 (29%) relapsed (including 10 deaths). The mean of both the single highest node tumour load (and total nodal tumour load), as measured by CK19mRNA copies/ul on OSNA, were significantly higher at 90,000 (98,300) for those who relapsed versus 23,100 (25,100) for those without relapse (p=0.027). Conclusions The OSNA assay is an accurate tool for axillary SLN analysis in patients after NAC and was helpful in intra-operative axillary management. OSNA reduces the need for a second surgery for AL in 20% of breast cancer patients with a positive-SLN after NAC and might offer additional prognostic value. Reference 1. NCCN. National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology Breast Cancer.2016.Version 2.2016. Citation Format: Muscara F, Christaki G, Richardson C, O'Connell R, Padmanabhan P, Warwick J, Lee Y, Smith I, Nerurkar A, Osin P, Krupa K, Rusby J, Roche N, Gui G, MacNeil F, Barry P. Clinical utility of one-step nucleic acid amplification (OSNA) in axillary surgery after neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P3-03-14.

Gemtuzumab Ozogamicin: Back Again

Despite the recent onslaught of approved medications in oncology, acute myeloid leukemia (AML) has been a disease state bereft of pharmaceutical development for decades. The long-standing first-line regimen, 7 + 3, was developed in 1973. A group of four physicians at Roswell Park Memorial Institute built upon prior combinations of daunorubicin and cytarabine to find the optimal combination of 7 days of cytarabine and 3 days of daunorubicin (Lichtman, 2013). This regimen has undergone multiple modifications and patient performance status-based stratifications, but has remained the first-line therapy for AML for the past 45 years. In September 2017, gemtuzumab ozogamicin returned to market and shortly thereafter was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for AML, to be administered in combination with 7 + 3, and as monotherapy for both newly diagnosed and relapsed patients with acute myeloid leukemia (NCCN, 2018; US Food & Drug Administration, 2017). Gemtuzumab ozogamicin continues to be explored in various leukemia settings and is a welcomed addition to the currently available treatment options for AML.

Repurposing Ponatinib as a Potent Agent against KIT Mutant Melanomas.

Rationale: Mutations in KIT, a major cancer driver gene, are now considered as important drug targets for the treatment of melanomas arising from mucosal and acral tissues and from chronically sun-damaged sites. At present, imatinib is the only targeted drug for KIT-mutation-bearing melanomas that is recommended by the National Comprehensive Cancer Network (NCCN) Clinical Practice guidelines. Patients with KIT mutations, however, are either insensitive or rapidly progress to imatinib insensitivity, which restricts its clinical use. Thus, effective inhibitors of KIT-mutation-bearing melanomas are urgently needed.Methods: A cohort of patient-derived tumor xenograft (PDX) models and corresponding PDX-derived cells (PDCs) from patients with melanomas harboring KIT mutations (KITV560D, KITK642E and KITD816V) were established, characterized, and then used to test the in vitro and, subsequently, in vivo inhibitory effects of a panel of known KIT inhibitors.Results: Ponatinib was more potent than imatinib against cells bearing KIT mutations. In vivo drug efficacy evaluation experiments showed that ponatinib treatment caused much stronger inhibition of KIT-mutation-bearing melanomas than did imatinib. Mechanistically, molecular dynamics (MD) simulations revealed a plausible atomic-level explanation for the observation that ponatinib has a higher affinity for the KITD816V mutant protein than does imatinib.Conclusions: Our study of KIT-mutation-and KITWT-bearing melanomas demonstrates that ponatinib is a far more potent inhibitor than is imatinib for KIT-mutation-bearing melanomas and thus underscores that ponatinib should be given priority consideration for the design of precision treatments for melanoma patients triaged to have KIT mutations. Moreover, our work provides a rationale for undertaking clinical trials to examine the repurposing of ponatinib, which is already approved for use in leukemia, for use in treating a large subset of melanoma patients.

Hypopharyngeal carcinoma: Do you know your guidelines?

Hypopharyngeal carcinoma is relatively rare, representing approximately 3% of all head and neck malignancies. It also is characterized by having one of the worst prognoses at time of diagnosis. This is largely due to its tendency for late presentation. This article will review current literature including as well as the National Comprehensive NCCN Guidelines Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines) for the treatment of hypopharyngeal cancer. Hypopharyngeal cancer often presents in an advanced stage and its prognosis is notoriously poor. Treatment goals are similar to other carcinomas of the head and neck and treatment typically involves multiple modalities including surgery, radiation, and chemotherapy. Organ sparing nonsurgical therapy has shown comparable survival outcomes to surgery in early stage hypopharyngeal cancer. Treating hypopharyngeal cancer remains a challenging prospect for the head and neck oncologist. A multidisciplinary approach is essential due to the necessity of combined therapy treatment protocols. There is opportunity for novel treatments and prospective trials to improve outcomes in hypopharyngeal carcinoma. Disease prevention by targeting environmental risk factors is likely to have the greatest impact in this disease.