Factor In Treatment Selection Research Articles

Decompression-first or direct enucleation: The choice of treatment for medium-sized odontogenic jaw cysts

BackgroundThe treatment of medium-sized odontogenic jaw cysts is inconsistent at present. Two main treatments, namely decompression and enucleation, are used overlappingly. This retrospective analysis aims to provide useful references for technique selection for future management of medium-sized odontogenic jaw cysts. MethodsOdontogenic cysts with lesion sizes ranging 2–4 cm were included. The clinical and radiological data of the patients were reviewed. Decompression-first and direct enucleation treatments were the two main surgical techniques. The preoperative parameters and postoperative outcomes were compared between the two groups. ResultsOut of 69 patients included, 40 (58 %) were in the decompression group and 29 (42 %) in direct enucleation group. The logistic regression analysis of preoperative parameters demonstrated that the maximum lesion size and the chief surgeon's preference could affect the selection of surgical techniques for medium-sized cysts (P < 0.05). Receiver operating characteristic curve analyses demonstrated that a lesion size >2.5 cm was the best cutoff value for predicting a decompression selection. Most postoperative outcomes differed significantly between the two groups (P < 0.05). Lower-risk anesthesia, shorter hospitalization, tooth function protection, and fewer neurosensory impairments were decompression-favoring outcomes. However, more follow-up visits, more postoperative X-rays, and longer postoperative care were outcomes against decompression. The recurrence rate was low and did not differ significantly between the two groups (P > 0.05). ConclusionsThere is no apparent preference for treating medium-sized jaw cysts. The maximum lesion size is a moderate-impact factor for treatment selection. A tendency to prefer decompression-first with larger lesion size was found in medium-sized jaw cysts. The advantages of teeth preservation and low neurosensory impairment of decompression were verified in the medium-size jaw cysts. The burden of postoperative care should be considered when selecting decompression.

Expert Consensus on Comprehensive Early Rhythm Control in Addition to Guideline-Based Care for Atrial Fibrillation: A Modified Delphi Survey

Atrial fibrillation (AF) practice guidelines recommend a rhythm-control strategy to improve symptoms and quality of life, noting the side effects of antiarrhythmic drugs and catheter ablation. Emerging evidence indicates that comprehensive early rhythm control with antiarrhythmic drugs or catheter ablation is associated with a lower risk of adverse cardiovascular outcomes versus the usual care. Using an online modified Delphi survey approach, perspectives and expert consensus among electrophysiologists were examined through a series of ranking and likelihood questions around treatment decision-making on (1) the use of comprehensive early rhythm-control strategies in patients with AF based on guidelines and emerging research and (2) treatment selection factors. A panel of 17 electrophysiologists reached a consensus on using early rhythm control (median 90, interquartile range 14) based on the view that early intervention improved cardiovascular outcomes (mean rank 1.6 of 3, 82% within 1 SD) and symptoms (1.8 of 3, 41%). AF-related symptoms were identified as the most important in making a treatment initiation decision (1.1 of 7, 88%), followed by AF type (2.5 of 7, 82%). Participants were most likely to initiate treatment at AF symptom onset (median 80; interquartile range 6). In making treatment selection decisions, participants ranked short-term/long-term safety (1.9 of 7, 88%) and efficacy (1.8 of 7, 53%) as the top 2 considerations. In conclusion, experts were in favor of early rhythm control; however, additional research is needed to address the role that early rhythm-control strategies play in current AF treatment management algorithms.

Patient priorities and expectations of systemic therapy in metastatic renal cell carcinoma.

4560 Background: As treatment options for metastatic Renal Cell Carcinoma (RCC) have increased in number, selecting therapy has become more complicated. When prioritizing agents today, guidelines recommend selection based primarily on risk classification, as well as consideration of efficacy data, patient characteristics, quality of life, cost, and patient preference. Understanding how patients prioritize treatment selection and define treatment success is crucial to improving patient/provider communication and to improving future drug development. Methods: The survey was developed by the Kidney Cancer Research Alliance (KCCure) and was broadcast between 07/2022 and 09/2022 to patients via website, mailing lists and social media platforms. Those who agreed to participate were surveyed for demographics (age, gender, race, income, country) and clinical characteristics (date of the diagnosis, disease stage, treatment history). Descriptive statistics summarized the survey data. Results: 399 out of 1,062 patients surveyed had metastatic disease. 80% of patients were receiving or had received systemic therapy, 20% of patients had not yet received systemic therapy. 52% were female and 48% were male, with a median age of 57 years (range 28-86). Patients identified as white (89%) and living in the United States (86%). 69% of patients reported that they did not know their IMDC or risk status, 10% were favorable risk, 11% were intermediate risk and 10% were poor risk. When asked to select the most important outcome for treatment selection on a rank-choice scale from 1 to 8, the chance to eliminate all evidence of disease (complete response) scored highest (6.6), followed by durability of response (5.1), improved quality of life (5.0), rapid reduction of tumors (4.9), ability to go off therapy (4.2), low risk of toxicity (4.0) and reduction of tumor symptoms (4.0). Patients ranked low cost as the least important factor in selecting treatment (2.3). 70% of patients defined “long-term" response to therapy as five years or longer, and over a quarter of patients (26%) defined long-term response as 10 years or longer. When asked to define treatment success, patients rank radiological reduction in tumor size (83%) as the most important factor, followed by stable disease (67%), improved quality of life (48%) and the ability to return back to work (22%). The lowest ranked choice was “I just trust my doctor” (17%). Conclusions: Most patients are not familiar with their risk classification and may not realize the significance of this factor in treatment selection. Patients rank complete response as the most important outcome/desire when considering treatment options. Cost is the least important factor for patients in selecting treatment. Patient perceptions of long-term response to therapy may differ from provider perceptions. More research is needed to improve patient/provider communication in the therapy selection process.

High tumor burden in patients with non-small-cell lung cancer: a Delphi survey among Spanish oncologists.

Aim: To define high tumor burden (HTB) in non-small-cell lung cancer. Methods: A total of fiveoncologists initiated the project, selecting 66 participants, and elaborated a questionnaire with 26 statements using the Delphi method with a 9-point Likert scale of agreement. Results: Factors with moderate strength of consensus wereidentified, including a sum of the longest diameter of lesions ≥10cm, elevatedLDH, hepatic involvement, lymphangitis carcinomatosis, brain involvement unapproachable with local techniques and pericardial effusion. There was a consensus against increases intumor markers and asymptomatic brain involvement being related to HTB. HTB was considered a relevant factor for treatment selection supporting thechoice of combination regimens versus immunotherapy only. Conclusion: In this Delphi study, experts defined several factors associated with HTB in non-small cell lung cancer.

Gonadotropin-releasing hormone analog therapies for children with central precocious puberty in the United States.

Gonadotropin-releasing hormone agonists (GnRHa's) are the standard treatment for children with central precocious puberty (CPP). We aim to present data on available GnRHa options with an easy-to-review table and discuss factors that influence treatment selection. Five GnRHa's are currently FDA-approved and prescribed in the US and published data suggest similar safety and efficacy profiles over the first year of treatment. One- and 3-month intramuscular (IM) leuprolide acetate (LA) have long-term safety and efficacy data and allow for flexible dosing. Six-month IM triptorelin pamoate offers a longer duration of treatment, but without long-term efficacy and outcome data. Six-month subcutaneous (SQ) LA combines a SQ route of injection and long duration of action but lacks long-term efficacy and outcome data. The 12-month SQ histrelin acetate implant avoids injections and offers the longest duration of action, but requires a minor surgical procedure with local or general anesthesia. Factors in treatment selection include route of administration, needle size, injection volume, duration of action, and cost. The current GnRHa landscape provides options with varying benefits and risks, allowing physicians and caregivers to select the most appropriate therapy based on the specific needs and concerns of the child and the caregiver. Agents have different advantages and disadvantages for use, with no one agent displaying superiority.

Parental perspectives on attention-deficit/hyperactivity disorder treatments for children.

This study investigated parental perspectives and experiences on the evaluation and treatment process associated with attention-deficit/hyperactivity disorder (ADHD). Five hundred sixty-eight parents of youth 2-28years-old (M = 9.37; SD = 4.11) diagnosed with ADHD responded to a 14-item online survey about their child's diagnosis and treatment. Parents reported that they had tried an average of 4.49 interventions (SD = 2.63). Parents further shared factors in treatment selection, most helpful parenting strategies, and preferences for types of treatments and treatment targets. A majority of parents reported incorporating many non-traditional strategies (e.g., exercise, healthy eating, outdoor activities) with goals of improving their child's coping skills, study habits, and anger management. The findings show that treatment choices were often selected based on trust in the provider, research support, and the child's preference. Given parental preferences for non-traditional strategies, treatment development efforts should consider these strategies as a component of a broader multimodal treatment approach to ADHD.

Real-World Treatment Selection Factors and 7-Year Clinical Outcomes between Percutaneous Coronary Intervention and Coronary Artery Bypass Graft Surgery in Left Main Disease.

Background: The decision-making factors and long-term clinical outcomes between PCI and CABG in left main (LM) disease are still not well defined in the real world. Methods: We evaluated consecutive patients (n = 230) with LM disease either treated by PCI (n = 118) or CABG (n = 112). The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiac death, spontaneous myocardial infarction (MI), stroke, and target vessel revascularization (TVR) for 7 years. Results: In the multivariate-adjusted analysis, the presence of intermediate EuroSCORE II and high SYNTAX scores predisposed to CABG. Isolated LM disease was associated with receiving PCI. The PCI group had a similar rate of MACE (HRadj 0.97, 95% CI [0.48–1.94], p = 0.92) and a lower tendency of hard MACE (HRadj 0.49, 95% CI [0.22–1.07], p = 0.07) compared to the CABG group, mainly due to the balance between a higher rate of TVR (HRadj 9.71, p = 0.02) and a lower rate of stroke (HRadj 0.22, p = 0.09) with the PCI group than in the CABG group. Conclusions: The decision making of treatment strategy was made based on clinical and angiographic factors. The selected patients who received PCI showed similar MACE and trend of a lower rate of composite hard endpoints despite multivariate adjustment.

Patient and physician perspectives guiding intra-articular treatment choice in knee osteoarthritis: stakeholders are aligned on treatment priorities but have different assessments of treatment effect

ObjectivesKnee osteoarthritis (OA) is a leading cause of health-related disability. In the absence of curative non-operative therapies, treatment goals are limited to symptom relief. Data are limited on how patients and physicians prioritise available treatment options. We assessed patients’ preferences for and physicians’ attitudes towards intra-articular treatments including corticosteroids (IACS), an extended-release corticosteroid (TA-ER) and hyaluronic acids (IAHA).MethodsWe conducted a prospective, IRB-exempt, double-blind survey of patients with and providers who treat knee OA. Respondents were required to have received or prescribed TA-ER in a non-trial setting. We evaluated patients’ OA history, impact of knee OA and treatment preferences, and physicians’ decision-making and prescribing experiences.ResultsOf the 97 patient participants, mean age was 56 years, 70.0% were women, 75.0% had bilateral knee OA and 46.4% were diagnosed over 5 years ago. Of the 50 physician participants, 42.0% were orthopaedic surgeons, 34.0% were rheumatologists and 60.0%, on average, treat 50+ patients with knee OA per month. Treatment selection factors considered ‘very important’ to patients and physicians included disease severity (88.7%, 82.0%), impact on quality of life (88.7%, 72.0%), disease extent (84.5%, 54.0%) and activity level (80.4%, 64.0%). A majority (93.8%) of patients indicated moderate to severe difficulty with their knees. Fewer patients (76.3%) reported shared decision making compared with physicians (92.0%). Half (50.5%) of the patients reported that they experienced months of pain relief with TA-ER, 27.7% with IACS and 18.8% with IAHA. Physician assessments were consistent but estimated a greater duration of treatment effects than that reported by patients across all therapies.ConclusionWhile knee OA has a tremendous impact on patients, there are significant unmet treatment needs. The increasing use of patient-reported outcomes will allow patients and physicians to track pain and functional status over time and across therapies, improving shared decision-making.

Brentuximab vedotin with chemotherapy in adolescents and young adults (AYAs) with stage III or IV Hodgkin lymphoma: A subgroup analysis from the phase 3 Echelon-1 study.

7528 Background: Hodgkin lymphoma (HL) is a rare disease that commonly occurs in adolescents and young adults (AYAs) which is typically defined as 15 to 39 years. Given their young age at presentation, key factors in treatment selection include a high cure rate and limiting long-term toxicities. Brentuximab vedotin (Adcetris®; A) is a CD30-directed ADC approved in combination with doxorubicin, vinblastine, and dacarbazine chemotherapy (A+AVD) for adults with previously untreated stage III/IV cHL based on results from the phase 3 ECHELON-1 trial. Recent 5-year data demonstrated a significantly improved PFS per investigator (INV) vs doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) (HR, 0.69; 95% CI, 0.54–0.9; P = 0.003) (Straus 2020). Here we describe key efficacy and safety results for AYA pts enrolled in ECHELON-1. Methods: ECHELON-1 (N = 1334) is a global, open-label, multicenter, randomized trial of pts with previously untreated stage III/IV cHL. A total of 771 AYAs (57.8%) received either A+AVD (n = 396) or ABVD (n = 375) with a PET scan after cycle 2 (PET2). An analysis of PFS (time from randomization to progression or death from any cause) per INV was conducted. Results: After a median follow-up of 60.7 months (95% CI, 60.4-61.0), there was a 36% reduction in the risk of progression or death in AYAs receiving A+AVD vs ABVD (HR 0.64; 95% CI, 0.45-0.92; P = 0.013) with a 5-year PFS of 86.3% vs 79.4%, respectively, similar to the ITT population. The PFS benefit of A+AVD vs ABVD was independent of PET2 status; PET2 positivity (Deauville 4-5) was 6% and 8%, respectively. On the A+AVD arm, 81 AYAs (20%) had at least 1 subsequent anticancer therapy vs 96 AYAs (26%) on the ABVD arm; 26 AYAs (7%) received subsequent high dose chemotherapy and autologous stem cell transplant vs 32 AYAs (9%) on the A+AVD and ABVD arms, respectively. Resolution or improvement of peripheral neuropathy (PN) were similar in both arms; 224 AYAs (88%) on the A+AVD had resolution or improvement of PN vs 133 AYAs (89%) on the ABVD arm. Ongoing PN was predominantly Gr 1 (62%) and Gr 2 (26%), with 8 AYAs (13%) on the A+AVD arm and 1 AYA (5%) on the ABVD arm reporting ongoing Gr 3 PN. Finally, 7 AYAs (1.8%) and 5 AYAs (1.4%) on the A+AVD and ABVD arms, respectively, reported a secondary malignancy. Subsequent pregnancies were reported in female pts (44 A+AVD; 26 ABVD) and partners of male pts (31 A+AVD; 30 ABVD). No stillbirths were reported. All but 1 pt in each arm was &lt; 40. Conclusions: Consistent with the ITT population, AYAs treated with A+AVD compared to ABVD had a durable PFS benefit at this significant 5-year milestone. No impact on the rate of secondary malignancies and a numerically greater number of pregnancies were observed, outcomes of interest to AYAs. Additionally, the majority of PN events improved or resolved over time. A+AVD should be considered a treatment option for AYAs with stage III/IV cHL. Clinical trial information: NCT01712490.

The characteristics and impact of hard-to-heal wounds: results of a standardised survey.

The effective management of hard-to-heal wounds has increasingly important implications for those who provide wound care services within healthcare systems. The burden of wounds in the population continues to grow, as does the demand for wound care, against a backdrop of cost constraints and increasing expectations. The need to improve both outcomes and efficiency in wound care is therefore paramount and the time taken to heal wounds is an important factor in determining both. Survey methodology was used to collect data across 10 community wound care providers in the UK, Ireland, Finland, Norway and Denmark between February and August 2017. This allowed for analysis of wounds and their characteristics, dressing selection and nursing practice across a typical wound caseload. Data from 1057 wounds demonstrates that the characteristics and consequences of hard-to-heal wounds are different from improving wounds. However, wounds are, in general, treated in the same way, irrespective of whether they are hard-to-heal or improving, suggesting that the healing status of a wound is not a major factor in treatment selection. Early intervention to return hard-to-heal wounds to a healing trajectory may be a useful approach to improving efficiency in wound care.

A prospective study of the cognitive and psychiatric effects of pituitary tumours and their treatments

Neurocognitive complaints are common in patients with pituitary tumours, particularly in memory and concentration. Past studies have shown impairments in executive function and memory, but it is not clear whether these result from direct effects of the tumour (pressure or hormonal secretion), incidental damage from radiotherapy or surgical treatments, and/or mediating psychiatric factors. This study assessed cognitive function and psychiatric state of 86 pituitary tumour patients and 18 healthy controls, pre and post-treatment, to examine the effects of tumour aetiology and treatment type. No significant cognitive impairments were found, except on verbal recognition memory. Patients with Cushing’s disease showed lower verbal recognition memory than the other groups pre-treatment, but improved at follow-up. This was (at least partially) accounted for by an improvement in depression scores. Patients who were treated with surgery showed poorer verbal recognition memory than controls across all (pre- and post-treatment) time-points. Overall findings of minimal cognitive impairment in patients with pituitary tumours may reflect improved diagnostic and treatment techniques in recent years. We suggest that the verbal memory impairments identified in the Cushing’s group may result from increased cortisol (directly, or mediated by depression). In the surgical groups, verbal memory impairments appeared to pre-date treatment. This may relate to treatment selection factors, rather than harmful effects of surgery itself.

Clinical outcomes and surgical preferences for breast-conserving surgery and mastectomy: a propensity score-matched analysis

Abstract Background While numerous randomized controlled trials have demonstrated long-term survival rates for patients with early-stage breast cancer treated with breast-conserving surgery (BCS) comparable to mastectomy, the latter remains the most prevalent surgical option to treat early-stage breast cancer in Thailand. Objectives To investigate the potential determinants affecting the decision on selecting BCS or mastectomy for the treatment of early-stage breast cancer and to compare the disease-free survival and overall survival between the treatments using a propensity score-matched analysis. Methods Patients diagnosed nonmetastatic breast cancer at the Queen Sirikit Breast Cancer Center from January 2006 to December 2015, were retrospectively identified and grouped intro patients who received BCS or mastectomy. After propensity score matching, 356 BCS and 209 mastectomy patients were identified, and statistical analysis was conducted to determine treatment selection factors and compare disease-free and overall survival. Results Disease-free survival and overall survival in months comparing BCS and mastectomy were not statistically different with P values of 0.11 and 0.77, respectively. Determinants of treatment selection found that younger age, surgeon preference, smaller tumor size, and lower tumor grade were statistically significant factors in the selection of BCS over mastectomy. The majority of surgeons had a preference for one treatment over the other (P &lt; 0.001). Conclusion The outcome of BCS is comparable to mastectomy in early-stage breast cancer patients. Key determinants affecting the selection of treatment were identified to be patient age, characteristics of the tumor, and surgeon’s preference.

Chemotherapy in Esthesioneuroblastoma/Olfactory Neuroblastoma: An Analysis of the Surveillance Epidemiology and End Results (SEER) 1973-2015 Database.

Chemotherapy has been proposed as an adjunct to primary local therapy in esthesioneuroblastoma (ENB)/olfactory neuroblastoma (ON), but its role has not been precisely defined. Here, we evaluated its role in ENB treatment. The Surveillance Epidemiology and End Results (SEER) database was queried for ENB/ON (International Classification of Diseases-3 9522). Cases met criteria for inclusion if they were unique, had a primary location in the nasal cavity, and had adequate information for Kadish staging derivation. Univariable and multivariable Cox analyses assessed chemotherapy treatment effect on disease-specific survival (DSS) and overall survival (OS). Multiple imputation addressed missing data. A P<0.05 was designated for statistical significance. In adjusted multivariable analyses, chemotherapy treatment was associated with inferior DSS (hazard ratio [HR], 1.74; 95% confidence interval [CI], 1.21-2.51; P=0.003) and OS (HR, 1.71; 95% CI, 1.26-2.32; P=0.001). Among the subset with local or regional disease treated with surgery and/or radiation therapy, chemotherapy remained associated with inferior outcomes DSS (HR, 2.78; 95% CI, 1.63-4.74; P<0.001) and OS (HR, 2.18; 95% CI, 1.45-3.27; P<0.001). Chemotherapy treatment misclassification did not explain these findings. This analysis does not support chemotherapy to improve either DSS or OS in primary ENB/ON treatment, after controlling for known ENB prognostic factors available from SEER. Other prognostic and treatment selection factors could exist which were not controlled in these analyses. Chemotherapy could beneficially affect outcomes other than DSS or OS. Although the concerns have been expressed regarding chemotherapy treatment misclassification in SEER, their analyses did not identify such misclassification as an explanation for our findings.

Rapid Response of Biologic Treatments of Moderate-to-Severe Plaque Psoriasis: A Comprehensive Investigation Using Bayesian and Frequentist Network Meta-analyses.

IntroductionRapid improvement of psoriasis is valued by patients and should be considered to be an important factor in treatment selection. We investigated Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) response rates within the first 12 weeks of treatment to compare the rapid response of 11 biologic therapies for moderate-to-severe psoriasis using Bayesian and Frequentist network meta-analyses (NMA).MethodsA systematic literature review was conducted to identify phase 3, double-blind, randomized, controlled trials for adult patients with moderate-to-severe psoriasis treated with interleukin (IL)-17 (brodalumab, ixekizumab, secukinumab), IL-12/-23 (ustekinumab), IL-23 (guselkumab, risankizumab, tildrakizumab), or tumor necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, infliximab). Outcome measures extracted from 32 publications were ≥ 75, ≥ 90, or 100% improvement in PASI score (PASI 75, PASI 90, or PASI 100, respectively) at weeks 2, 4, 8, and 12 and DLQI (0,1), where score (0,1) indicates no effect on patient's life, at week 12. Bayesian NMA (BNMA) used fixed-treatment effect and random-baseline effect, normal independent models. Frequentist NMA (fNMA) was conducted as sensitivity analyses to test the robustness of the findings.ResultsBased on BNMA and fNMA, brodalumab and ixekizumab showed the most rapid treatment effects on PASI 75 at weeks 2, 4, and 8 and on PASI 90 and PASI 100 at weeks 2, 4, 8, and 12; ixekizumab overlapped with risankizumab on PASI 75 at week 12. Brodalumab, ixekizumab, and secukinumab yielded higher DLQI (0,1) gains at week 12 compared to all of the other biologics studied. Additional measures of quality of life were not assessed in this report.ConclusionsIxekizumab and brodalumab provide the most rapid response and earliest clinical benefit at week 2 among all of the biologics studied, including other biologic treatments such as secukinumab, ustekinumab, guselkumab, adalimumab, and etanercept. BNMA and fNMA results showed similar relative effect estimates and treatment rankings.FundingEli Lilly and Company.Electronic supplementary materialThe online version of this article (10.1007/s13555-019-00337-y) contains supplementary material, which is available to authorized users.

Abstract 3996: Search for prognosis prediction factors in treatment selection for elderly patients with EGFR negative advanced stage non-small cell lung cancer patients

Abstract Introduction: Since 40% of Japanese lung cancer patients are older than 75 years old, it is necessary to consider a specific strategy to treat such elderly lung cancer patients. From that aspect, it is very important to define frail or vulnerable elder populations who have lots of heterogenic health background in treatment of lung cancer. In this study, we have tried to identify prediction factors which significantly correlates to overall survival (OS) of such elderly advanced lung cancer patients by using of patient status and laboratory data before treatment. Objects and methods: Patients more than 75 years old who enrolled in this retrospective study were diagnosed as an advanced and EGFR negative non-small cell lung cancer during 2013-2017, and they were not available for any molecular targeted therapeutics. OS of best supportive care (BSC) cohort and chemotherapy with Docetaxel monotherapy and more cohort from those elderly patients were analyzed by Kaplan-Meier analysis. Results: Clinical Question 1; What is a prediction factor for OS of BSC patients? Answer 1; From analysis of 29 BSC patients (age 15-94 years old, median 82), it is revealed that low performance status (PS =0,1) stage at diagnosis (p=0.03) are significantly correlated to longer OS, and also hypoalbuminemia is significantly correlated to worse OS (11 wks vs 35 wks). Age at diagnosis did not correlate to duration of OS. ( more vs less than 80 years old:15 wks vs 37 wks, P=0.13)Clinical Question 2; Does chemotherapy significantly prolong OS of elderly patients? Answer 2; Kaplan-Meier analysis of elderly patients (PS 0-2) less than 80 years old who were treated by chemotherapies at least with DOC monotherapy showed longer OS than that of 29 BSC patients ( 84 wk vs 15 wk, p=0.006). However, no significant difference to OS (p=0.378) has been observed to BSC patients in advanced stage with better PS (0-2). Multivariate analysis for OS indicated significant correlation of hypoalbuminemia (p=0.002), but no correlation of chemotherapy (p=0.202) has been observed. Conclusion: 1, EGFR mutation-negative advanced NSCLC patients elder than 80 years old who were treated by chemotherapies did not showed significantly longer OS than that of BSC patients. 2, PS and hypoalbuminemia before treatment may be prediction factors for longer OS of elder lung cancer patients. Citation Format: Yoshiko Kaneko, Takako Mouri, Nobuyo Tamiya, Tadaaki Yamada, Junji Uchino, Koichi Takayama. Search for prognosis prediction factors in treatment selection for elderly patients with EGFR negative advanced stage non-small cell lung cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3996.

Chemotherapy in the management of olfactory neuroblastoma/esthesioneuroblastoma: An analysis of the surveillance, epidemiology, and end results (SEER) 1973-2015 database.

e17573 Background: Olfactory neuroblastoma (ON) is a malignant tumor of nasal cavity arising in sensory neuroectodermal olfactory cells. Chemotherapy (CT) has been proposed as an adjunct to primary local therapy. Here, we investigated the role of CT in primary ON treatment. Methods: SEER was searched for ON (ICD-3 9522). Inclusion criteria were (1) unique cases; (2) primary nasal cavity tumor; (3) staging information; and (4) ability to derive Kadish stage. Abstracted covariates included sex, age, tumor grade, nodal status, year of diagnosis, derived Kadish stage, and treatment (surgery, radiotherapy (RT), CT). Outcomes included disease-specific (DSS) and overall (OS) survival. In SEER, CT and RT are classified as Yes vs No/Unknown. Uni- and multi-variable Cox analyses assessed CT treatment on DSS and OS, controlling for covariates noted above. To account for proportional hazards violations, such variables were either stratified or time-varying. Multiple imputation addressed missing data. A p &lt; 0.05 was designated for statistical significance. Analyses were conducted using Stata ver 12. Results: 797 ON cases were included. In univariable analysis, CT treatment (yes vs no/unknown) was associated with inferior DSS (HR 2.81, 95% CI 2.11 3.74, p &lt; 0.001) and OS (HR 2.03, 95% CI 1.63 2.54, p &lt; 0.001). In multivariable analyses, CT was again associated with inferior DSS (HR 1.74, 95% CI 1.21, 2.51, p = 0.003) and OS (HR 1.71, 95% CI 1.26, 2.32, p = 0.001). Limiting analysis to those with local/regional disease treated with local therapy (surgery and/or radiation), CT remained associated with inferior outcomes [DSS (HR 2.78, 95% CI 1.63, 4.74, p &lt; 0.001) and OS (HR 2.17, 95% CI 1.45, 3.27, p &lt; 0.001)]. Sensitivity analyses ruled out chemotherapy misclassification as an explanation for our results. Conclusions: Our analysis does not support the use of chemotherapy to improve either DSS or OS in primary ON treatment. We controlled for known ON prognostic factors available from SEER. Other prognostic and treatment selection factors could exist for which we did not control. Chemotherapy may also beneficially affect outcomes other than DSS or OS. While concerns have been expressed regarding CT treatment misclassification in SEER, our analyses did not identify such misclassification as an explanation.

Abstract 5781: A novel ERK1/2 inhibitor has potent activity in KRAS-mutant non-small cell lung cancer models

Abstract Non-small cell lung cancer (NSCLC) molecular profiling is a key factor in treatment selection. Although, patients with NSCLC tumors harboring EGFR or ALK mutations can benefit from personalized therapies, there are currently no approved targeted therapies for KRAS mutant tumors which occur in 25% to 30% of patients with NSCLC. The constitutive activation of the MAPK pathway in these tumors provides a rationale for targeting effectors such as MEK1/2 (MEK) or ERK1/2 (ERK). Inhibitor of MEK kinase have been tested clinically in KRAS-mutant NSCLC but results have been disappointing, possibly because compensatory signaling such as the reactivation of ERK is triggered following the inhibition of MEK, leading to cancer cell survival. Therefore, targeting ERK directly represents an attractive therapeutic approach. As previously described, we have developed a novel, potent and selective ERK inhibitor identified by fragment-based drug discovery which has potent activity in vitro and in vivo. Here, we demonstrate the activity of this lead compound in KRAS-mutant NSCLC models. Our novel ERK inhibitor was tested in a panel of 440 human cancer cell lines of which the KRAS NSCLC population was identified as particularly sensitive. 62% of the KRAS-mutant NSCLC cell lines tested, exhibited antiproliferative IC50s ranging from 1 nM to 500 nM. This lead compound also inhibited ERK downstream signaling in KRAS NSCLC models both in vitro and in vivo. Indeed, the phosphorylation level of the ERK substrate, RSK, was strongly decreased in HCC-44 and Calu-6 xenograft tumors 2h after oral administration of the lead compound at 50 mg/kg. Levels of pRSK remained below those of untreated tumors for up to 16h in HCC-44 tumors and 24h in Calu-6 tumors. We also confirmed that, the ERK inhibitor conferred a decrease in phosphorylation of ERK itself in both models. The inhibition of ERK signaling corresponded to significant anti-tumor activity in these models with a daily oral administration of 50 mg/kg compound leading to significant tumor regression in subcutaneous models of HCC-44 (18.3% T/C) and Calu-6 (8.9% T/C) xenograft tumors. This work demonstrates the in vitro and in vivo activity of a novel, highly potent, selective ERK inhibitor in models of KRAS-mutant NSCLC. These data support the further optimisation of this series of compounds for clinical development. Citation Format: Aurelie Courtin, Luke Bevan, Tom Heightman, Birikiti Kidane, Justyna Kucia-Tran, John Lyons, Sandra Muench, Alpesh Shah, Lukas Stanczuk, Neil Thompson, Nicola Wallis, Nicola Wilsher, Joanne Munck. A novel ERK1/2 inhibitor has potent activity in KRAS-mutant non-small cell lung cancer models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5781.

100P - Impact of perioperative fluoropyrimidines on the efficacy of capecitabine in patients with advanced breast cancer: A retrospective study

Background: It is unclear whether perioperative fluoropyrimidine (FP) use impacts the efficacy of capecitabine in advanced breast cancer treatment. Methods: Medical records of patients with advanced breast cancer who received capecitabine between 2008 and 2016 at National Cancer Center Hospital (Tokyo, Japan) were reviewed. Progression-free survival (PFS), overall survival (OS), tumor response, and adverse events (AEs) were compared between a FP group (prior perioperative FP use) and a non-FP group (no prior FP use). To evaluate the effect of prior perioperative FP use on survival outcomes, hazard ratios (HRs) for PFS and OS were estimated for the FP group compared with the non-FP group. Results: A total of 289 patients (FP group: n = 106; non-FP group: n = 183) were analyzed. Patient characteristics were similar between the two groups. The median recurrence-free interval (RFI) was 3.94 (range: 0.27-20.11) years in the FP group and 4.24 (range: 0.27-27.07) years in the non-FP group (p = 0.402). The FP group had poorer PFS than the non-FP group (univariate HR: 1.33; 95% confidence interval [CI]: 1.03-1.72, p = 0.028; multivariate HR: 1.33; 95% CI: 1.02-1.73; p = 0.034). However, OS was similar between the groups (univariate HR: 1.16; 95% CI: 0.84-1.62; p = 0.368; multivariate HR: 1.06; 95% CI: 0.74-1.51; p = 0.755). Multivariate HRs for PFS for the FP group with short RFI and long RFI (cutoff: RFI=4 years) separately were 1.56 (95% CI: 1.06-2.28; p = 0.025) and 1.20 (95% CI: 0.84-1.70; p = 0.326), respectively. With different cutoffs (RFI=3, 4, and 5 years), the ranges of adjusted HRs for PFS were 1.32-1.67 with short RFI, and 1.00-1.25 with long RFI. A trend for larger HR for the FP group with short RFI than with long RFI was also seen for OS with different cutoffs of RFI. The response rate (FP group vs. non-FP group) was 21.0% vs. 14.8% (p = 0.306), and the disease control rate was 59.9% vs. 54.5% (p = 0.422). There was no significant difference in AEs between the two groups. Conclusions: Capecitabine can be used for patients with advanced breast cancer with FP use history, as OS does not correlate with prior FP use. For patients with FP use history, RFI may be a relevant factor for treatment selection. Legal entity responsible for the study: National Cancer Center Hospital Funding: None Disclosure: All authors have declared no conflicts of interest.

Quantification of intratumoral heterogeneity of HER2 status in breast cancer.

1036 Background: Intratumoral heterogeneity (ITH) occurs as a consequence of epigenetic aberrations in tumor cells with genetic diversity. HER2 ITH can be classified into genetic (a mixture of tumor cells with and without HER2 gene amplification) and epigenetic ITH (a mixture of HER2 gene-amplified tumor cells with and without HER2 protein overexpression). However, the both effects of genetic and epigenetic ITH on HER2-targeted therapy have not been clearly demonstrated. In order to implement ITH as a referenced factor for treatment selection, the ITH quantification is necessary. Gene-protein assay (GPA), in which immunohistochemistry and dual in situ hybridization are simultaneously performed on a single slide, allows bright-field analyses of both gene and protein status. We aimed to quantify HER2 ITH by the combination of gene and protein status and clarify its clinical significance. Methods: Fifty three patients with HER2-positive breast cancer, who underwent neoadjuvant trastuzumab with chemotherapy, were examined. Five representative microscopic images were captured from a GPA slide of a pre-therapeutic biopsy material. All evaluable tumor cells in the images were scored according to the HER2 status determined by the combination of gene copy number and protein expression (Table). We investigated the relationship between the HER2 scores and pathological complete response (pCR) to the neoadjuvant treatment by the logistic analysis. Results: The average of HER2 scores, indicating the degree of the HER2 status, varied from 2.21 to 5.98. It was significantly related to pCR (Estimate: 1.21, Std. error: 0.46, RR: 3.34, P=0.009, 95%CI: 1.35-8.25). The standard deviation of HER2 scores, indicating the degree of the HER2 ITH, varied from 0.13 to 1.37. It was significantly related to pCR (Estimate: -2.09, Std. error: 0.83, RR: 0.12, P=0.012, 95%CI: 0.02-0.63). Conclusions: HER2 ITH, quantified by GPA, is a predictive factor for the therapeutic effect to trastuzumab-based treatment in HER2-positive breast cancer. [Table: see text]

Etiology, syndrome diagnosis, and cognition in childhood‐onset epilepsy: A population‐based study

SummaryObjectiveTo evaluate the prevalence of various etiologies of epilepsies and epilepsy syndromes and to estimate cognitive function in cases of childhood‐onset epilepsy.MethodsA population‐based retrospective registry study. We identified all medically treated children with epilepsy born in 1989–2007 in Finland's Kuopio University Hospital catchment area, combining data from the birth registry and the national registry of special‐reimbursement medicines. We reevaluated the epilepsy diagnoses and syndromes and gathered data on etiologies and cognitive impairment.ResultsWe identified 289 children with epilepsy. The annual incidence rate of epilepsies and epilepsy syndromes was 38 in 100,000, and the misdiagnosis rate was 3%. A specific etiology was identified in 65% of the cases, with a structural etiology accounting for 29% and a genetic or presumed genetic etiology for 32%. Most patients with unknown‐etiology epilepsy had focal epilepsy and were of normal intelligence. Intellectual disability was detected in 35% of cases, and only 17% in this group had an unknown etiology for the epilepsy. Electroclinical syndromes (mainly West syndrome) were recognized in 35% of the patients.SignificanceEpilepsy is a complex disease that encompasses many etiologies and rare syndromes. The etiology and specific epilepsy syndrome are important determinants of the outcome and key factors in treatment selection. Etiological diagnosis can be achieved for the majority of children and syndromic diagnosis for only a third.