Incidence Of BM Research Articles

Utilising Response Surface Methodology to Optimise Food Additives and Treatments Reduces Disease Caused by Penicillium digitatum and Penicillium italicum in ‘Valencia’ Oranges

Penicillium digitatum and Penicillium italicum are responsible for citrus green and blue moulds (GM and BM), respectively, which are major citrus postharvest diseases. The aim of this study was to develop an optimal dipping mixture of an aqueous solution of different food additives: sodium bicarbonate (SB), sodium benzoate (SBen), and potassium sorbate (PS), in combination with heat, to control GM and BM using response surface methodology. The ranges of SB (0.0%, 3.0%, 6.0%), SBen (0.0%, 0.5%, 1.0%), PS (0.0%, 0.5%, 1.0%) and temperature (20 °C, 35 °C, 50 °C) with a dipping time of 60s were tested for their impact on GM and BM on artificially inoculated oranges. Within these tested ranges, SB reduced GM severity and incidences of both GM and BM. PS affected BM severity and incidence, but not GM. SBen and temperature did not have impact on GM and BM. The most suitable food additive concentrations were identified to be 4.7% SB, 1.0% SBen and 0.7% PS, with a dipping solution temperature of 50 °C. This treatment was shown to reduce GM and BM incidence from 85 and 86% on control fruit dipped in tap water at 20 °C to 3 and 10%, respectively. Additionally, the severity of GM and BM was reduced from 64 and 26 mm on control fruit to <1 and 2.8 mm, respectively.

IMMU-02. IS DUAL AGENT IMMUNOTHERAPY SHIFTING THE EPIDEMIOLOGY OF MELANOMA BRAIN METASTASES? A REAL-WORLD ANALYSIS AND SINGLE-INSTITUTION VALIDATION

Abstract INTRODUCTION Dual agent immunotherapy (dIT) has been paradigm changing in melanoma brain metastasis (MBM). Recent clinical trials have supported the role of dIT for upfront management of small, asymptomatic MBM. Yet, its potential role in extending brain metastasis free survival and decreasing MBM incidence overall has been inadequately explored. Objective: To compare new brain metastasis incidence, median overall survival (OS), and brain metastasis free survival (BMFS) in melanoma patients treated with dIT versus single immunotherapy (sIT). METHODS A real-world deidentified database collating clinical information from 92 organizations (TriNetX, Inc) was queried. Melanoma patients without brain metastases prior to immunotherapy were stratified by treatment (anti-CTLA4 [sIT] and combination anti-CTLA4/ anti-PD1 [dIT]) and propensity score matched. A complementary single-institution retrospective cohort study analyzed melanoma patients treated from 2012-2019. The incidence of new asynchronous MBMs after immunotherapy initiation was compared. Median OS and BMFS were compared via log-rank tests and Cox proportional-hazards model. RESULTS TriNetX identified 8,686 melanoma patients who received immunotherapy (4,585 dIT; 4,101 sIT). MBM prevalence was 9.6%, and 15.6%, for the dIT and sIT cohorts, respectively (p < 0.0001). DIT was associated with a lower likelihood of developing MBM compared to sIT (OR [95%CI], 0.64 [0.61-0.77]). After propensity score matching on demographics and significant comorbidities, OS was not statistically different between treatment groups. On single-institution analysis, 222 melanoma patients were included (89 dIT; 45 anti-CTLA4; 88 anti-PD1). Patients were predominantly stage III at diagnosis (43%) with PD-L1 expression (51%) and BRAF (43%), and NRAS wildtype (50%) mutational status. BMFS was significantly extended in the dIT cohort compared to the anti-CTLA4 or anti-PD1 alone cohorts (406, 217, 139 days, respectively; p< 0.0001). On Cox-proportional hazards model, no covariates significantly contributed to the BMFS difference. CONCLUSION These data highlight the impact of combination anti-CTL4/ anti-PD1 immunotherapy in decreasing BM incidence in melanoma.

DO GENOMIC ALTERATIONS INflUENCE THE DEVELOPMENT OF BRAIN METASTASES IN ADVANCED AND METASTATIC NON-SMALL CELL LUNG CANCER? A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract AIMS Establish prevalence at diagnosis, and incidence of BM in patients with advanced and metastatic non-small cell lung cancer (NSCLC), stratified by genomic alterations. METHOD A systematic review and meta-analysis was conducted in accordance with PRISMA guidelines (PROSPERO ID CRD42022315915). Three databases were searched (Search date 30th April 2022). Prevalence at diagnosis, and per-patient year incidence of brain metastases were obtained, including patients with EGFR, ALK, KRAS, ROS1, RET, and other genomic alterations. Pooled incidence rates were calculated using random effects models. RESULTS Of 960 articles identified, 65 were included (24,784 patients). The combined BM prevalence at diagnosis was 28.6% (45 studies, 95% Confidence Interval [CI] 26.1-31.0). Median follow-up was 24 months (Interquartile range [IQR] 16-36 months). The combined incidence of BM development was 10.8% per year (40 studies, 95% CI 9.2- 12.6). The per-year incidence of new BM was 15.6%/year in the EGFR +ve group (16 studies, 95% CI 11.4-21.2), 17.0% in the ALK+ve group (7 studies, 95% CI 11.3-25.8), 9.8% in the KRAS +ve group (4 studies, 95% CI 5.5-17.5), 12.5% in the ROS1 +ve group (3 studies, 95% CI 5.7-27.6), and 11.8% in the RET +ve group (2 studies, 95% CI 8.0-17.5). Combined overall prevalence was 55.0% (21 studies, IQR 44.2-67.8). CONCLUSIONS This systematic review indicates a high rate of brain metastases in NSCLC and is the first and only study to describe incidence, stratified by genomic alterations. This will have a major clinical impact by stratifying brain imaging at staging and follow-up by patient subgroup, particularly in ALK and EGFR mutations.

P11.30.A Stereotactic Radiosurgery (SRS) for brain metastases in breast cancer: An evaluation of outcomes at a UK tertiary centre

Abstract Background Brain metastases (BM) occur in approximately 10-30% of patients with breast cancer (BC). Patients with advanced breast cancer are living longer, and the incidence of BM are increasing. Stereotactic Radiosurgery (SRS) has emerged as a strategy to treat BM. We evaluated the outcomes and potential prognostic factors of patients with BM treated with SRS. Material and Methods Retrospective review of patients treated with linac-based SRS for BM from BC in a single tertiary centre between August 2017-September 2021. Overall survival (OS), intracranial progression-free survival (IPFS), and prognostic factors were evaluated using Kaplan-Meier analysis, log-rank test, and Cox proportional-hazards model. Results 76 patients were included in the analysis. Out of these, 56 had first-line local treatment with SRS, either as primary (n=34) or adjuvant to surgery (n=22). Median age was 58 years old (range 37-86), and 88% had PS 0/1. One-year survival rate was 56%. Median OS and IPFS from SRS was 16 months (95% CI 8-24) and 7 months (95% CI 2-12), respectively. However, there were significant differences in OS (p<0.001) and IPFS (p=0.001) based on molecular subtypes. Patients with triple-negative breast cancer (TNBC) (n=14) had median OS of 7 months (95% CI 2-12), ER+/HER2- (n=22) median OS of 22 months, ER-/HER2+ (n=8) median OS of 4 months (95% CI 0-9), and ER+/HER2+ (n=11) median OS of 36 months. Similar trend was seen with IPFS. Patients with progressive extracranial disease compared to stable disease had shorter median OS (4 months vs 23 months, HR 2.4, p=0.01) and median IPFS (4 months vs 13 months, HR 2, p=0.03). Age ≥65 years was associated with shorter median OS (4 vs 23 months, HR 2.3, p=0.02). Patients with ≥4 brain metastases had shorter IPFS (4 months vs 11 months, HR 2.4, p=0.012), but no significant difference in OS. Volume of metastases did not affect outcome in this series. 30% of patients progressed intracranially after first-line SRS. 94 % had out-of-field recurrences, and 6% in-field recurrences. 59% had further SRS, 12 % WBRT, 6% surgery, and 23% had no further local treatment. 26 patients had second-line local treatment with SRS after first-line SRS (n=9), WBRT (n=9), or surgery +/- WBRT (n=8). There were no significant differences in outcome based on the modality of first-line local treatment. Conclusion SRS is an effective treatment for BM from BC. There were significant differences in survival based on age, molecular subtypes, and extracranial disease status.

Incidence of Brain Metastases in Women Treated With Neoadjuvant Chemotherapy for Breast Cancer: Implications for Screening

PurposePatients with metastatic breast cancer may develop brain metastases. Our study identified high-risk patients to refine selection criteria for BM screening approaches. PatientsWe reviewed breast cancer patients treated with neoadjuvant chemotherapy (NAC) at a single university center between 2005 and 2019. MethodsCompeting risks analysis was performed with the Fine and Gray model to analyze the cumulative incidence of BM and loco-regional recurrence. Overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and log-rank tests. Multivariable analysis was performed with Cox proportional hazards regression to identify factors predictive for development of BM. Statistical significance was determined as a 2-sided P value of <.05. ResultsIn total, 112 patients experienced distant failure (DF) and 49 patients developed BM. Twenty patients with BM (41%) presented with symptoms requiring craniotomy +/- whole brain radiation treatment. Patients with BM were significantly more likely to have local (P < .01) and regional (P < .01) failure. On multivariable analysis, age <40 years (P = .011), presence of lung metastases (P < .0001), and residual nodal disease with >4 lymph nodes positive after NAC (P = .024) all predicted for increased likelihood of BM. Patients with these criteria had higher likelihoods of having BM (P = .013) and worse PFS (P = .044). On multivariable analysis for OS, presence of lung metastases was the most significant predictor of poor outcome (P < .0001). ConclusionWe propose a study of screening brain MRI for young (<40 years) patients with breast cancer receiving NAC and patients who develop metastatic disease post-NAC, especially those with lung involvement.

Brain Metastases among Cancer Patients Diagnosed from 2010-2017 in Canada: Incidence Proportion at Diagnosis and Estimated Lifetime Incidence.

The incidence of BM among Canadian cancer patients is unknown. We aimed to estimate IP of BM at the time of cancer diagnosis and during the lifetime of patients with selected primary cancers. Data on BM at diagnosis from 2010–2017 was obtained from the CCR. Site-specific IPs of BM were estimated from provincial registries containing ≥90% complete data on BM. The CCR IP estimates and the IP estimates from literature were applied to the total diagnosed primary cancers to estimate the number of concurrent BM and lifetime BM from 2010–2017 in Canada, respectively. The annual average number of patients with BM at diagnosis from all cancer sites was approximately 3227. The site-specific IPs of BM at diagnosis were: lung (9.42%; 95% CI: 9.16–9.68%), esophageal (1.58%; 95% CI: 1.15–2.02%), kidney/renal pelvis (1.33%; 95% CI: 1.12–1.54%), skin melanoma (0.73%; 95% CI: 0.61–0.84%), colorectal (0.22%; 95% CI: 0.18–0.26%), and breast (0.21%; 95% CI: 0.17–0.24%). Approximately 76,546 lifetime BM cases (or 5.70% of selected fifteen primary cancers sites) were estimated to have occurred from the 2010–2017 cancer patient cohort. These findings reflect results of population analyses in the US and Denmark. We recommend improved standardization of the collection of BM data within the CCR.

Impact of Low-Dose Computed Tomography Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis

IntroductionBrain metastasis (BM) is one of the most common metastases from primary lung cancer (PLC). Recently, the National Lung Screening Trial revealed the efficacy of low-dose computed tomography (LDCT) screening on LC mortality reduction. Nevertheless, it remains unknown if early detection of PLC through LDCT may be potentially beneficial in reducing the risk of subsequent metastases. Our study aimed to investigate the impact of LDCT screening for PLC on the risk of developing BM after PLC diagnosis. MethodsWe used the National Lung Screening Trial data to identify 1502 participants who were diagnosed with PLC in 2002 to 2009 and have follow-up data for BM. Cause-specific competing risk regression was applied to evaluate an association between BM risk and the mode of PLC detection—that is, LDCT screen-detected versus non-LDCT screen-detected. Subgroup analyses were conducted in patients with early stage PLC and those who underwent surgery for PLC. ResultsOf 1502 participants, 41.4% had PLC detected through LDCT screening versus 58.6% detected through other methods, for example, chest radiograph or incidental detection. Patients whose PLC was detected with LDCT screening had a significantly lower 3-year incidence of BM (6.5%) versus those without (11.9%), with a cause-specific hazard ratio (HR) of 0.53 (p = 0.001), adjusting for age at PLC diagnosis, PLC stage, PLC histology, and smoking status. This significant reduction in BM risk among PLCs detected through LDCT screening persisted in subgroups of participants with early stage PLC (HR = 0.47, p = 0.002) and those who underwent surgery (HR = 0.37, p = 0.001). ConclusionsEarly detection of PLC using LDCT screening is associated with lower risk of BM after PLC diagnosis on the basis of a large population-based study.

Abstract PS7-87: Incidence, treatment and survival of patients with brain metastases at initial metastatic breast cancer diagnosis: A real-world experience in national cancer center, China

Abstract Background: To characterize the incidence, treatment and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. Methods: The China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 to 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. Results: Brain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40 -4.04; p &amp;lt;0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02-3.51; p =0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52-6.87; p =0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p=0.09). Factors that independently decreased BM death risk were ECOG&amp;lt;2, brain metastases only and multidisciplinary treatment. Conclusion: HER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive or triple-negative diseases or with extensive extracranial metastases. First-line TKI and multidisciplinary treatment helped to extend survival. Citation Format: Yiqun Li, Qiao Li, Hongnan Mo, Xiuwen Guan, Shaoyan Lin, Zijing Wang, Yimeng Chen, Ye Zhang, Dainan Zhang, Shanshan Chen, Ruigang Cai, Jiayu Wang, Yang Luo, Ying Fan, Peng Yuan, Pin Zhang, Qing Li, Fei Ma, Binghe Xu. Incidence, treatment and survival of patients with brain metastases at initial metastatic breast cancer diagnosis: A real-world experience in national cancer center, China [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-87.

Incidence, risk factors and survival of patients with brain metastases at initial metastatic breast cancer diagnosis in China

PurposeTo characterize the incidence, risk factors and survival of patients with brain metastases at initial diagnosis of metastatic breast cancer (MBC) in China. MethodsThe China National Cancer Center database was used to identify 2087 MBC patients diagnosed between 2003 and 2015. Clinicopathological features, treatment and survival information were extracted. Multivariable logistic and Cox regression were performed to determine factors predictive of brain metastases at MBC diagnosis and survival, respectively. ResultsBrain metastases occurred in ninety patients (4.3%) at MBC diagnosis, and in 27 patients (2.5%), 42 patients (7.2%) and 21 patients (5.2%) with hormone receptor positive, human epidermal growth factor receptor 2 negative (HR + HER2-), HER2-positive and triple negative breast cancer (TNBC), respectively. HER2-positive subtype (OR = 2.38; 95% CI 1.40–4.04; p < 0.0001), TNBC subtype (OR = 1.89; 95% CI 1.02–3.51; p = 0.005), and metastases to all three sites of bone, liver and lungs (OR = 3.23; 95% CI 1.52–6.87; p = 0.002) were shown to increase the risk of BM at MBC diagnosis. Median survival after BM was 23.7 months. First-line tyrosine kinase inhibitors (TKI) improved survival compared to trastuzumab-based regimen (44.9 vs 35.4 months, p = 0.09). Factors that independently decreased BM death risk were ECOG<2, brain metastases only and multidisciplinary treatment. ConclusionHER2-positive and TNBC subtypes have a higher incidence of BM at initial MBC diagnosis. Brain screening might be considered in patients with HER2-positive disease at MBC diagnosis, and further prospective randomized study is warranted.

EXTH-06. INTEGRATED MOLECULAR PROFILING REVEALS TARGETABLE MOLECULAR ABNORMALITIES SHARED ACROSS MULTIPLE HISTOLOGIES OF BRAIN METASTASIS

Abstract Brain metastases (BMs) occur in approximately 20–40% of patients with advanced cancer, and the estimated prevalence of new BMs in United States is between 200,000–300,000 per year. While the incidence of BM has increased over the past decades due to improvements in brain tumor detection technology, the prognosis is still very poor with the median overall survival times from weeks to few months. Therefore, identification of the precise molecular landscape and therapeutic targets for BMs is absolutely essential in tangible improvement of patient management. Here, we performed integrated genomic, transcriptional, and proteomic profiling in a cohort of lung, breast, and renal cell carcinomas consisting of both BMs and patient-matched primary or extracranial metastatic tissues to identify shared cellular and molecular factors driving BMs across distinct primary tumor histologies. Although the comprehensive analysis identified the unique genomic, transcriptional and proteomic landscapes according to the different histopathologies, elevated PI3K/AKT and RAS/MAPK signaling was observed as a generalizable feature across the entire specimen cohort, along with relative immunosuppression and metabolic upregulation of the electron transport chain (ETC). Interestingly, immunosuppression via T cell depletion was significantly associated with unfavorable prognosis of patients with BMs, and ETC inhibition as the prospective therapeutic target for BM patients was demonstrated using in vitro and in vivo disease models. Taken together, our findings suggest that abnormalities involving oncogenic signaling, metabolism, and the immune microenvironment are shared across multiple histologies of BMs, and may be amenable to therapeutic targeting.

QOLP-01. OUTCOME ASSESSMENT OF MULTIDISCIPLINARY BRAIN TUMOR BOARD MEETING RECOMMENDATIONS FOR BRAIN METASTASIS: IS THERE A GAP?

Abstract BACKGROUND Brain metastasis (BM) is the most common form of brain cancer affecting 20-40% of cancer patients. Advancements in cancer therapy has prolonged survival but BM incidence has increased. BM management requires a multidisciplinary approach to individualize care via an ever-growing sum of surgical, radiation, and systemic therapy options. Consensus is achieved by multidisciplinary tumor board meeting (MTBm). Nevertheless, BM diagnosis predicts poor prognosis. Palliative Care (PC) is essential for proper BM management. Yet, formal PC assessment may not be available for MTBm. We evaluated whether MTBm consensus recommendations were followed. RESULTS Our weekly MTBm discussed 157 BM cases during 2019 (median age: 64 years [range 28-91], male/female: 82/75). The most common primary diagnosis was lung (n=49, 31%), breast (n=24, 15%), melanoma (n=16, 10%). The majority was newly diagnosed BM (n=143, 91%). MTBm recommendations were divided into three not-mutually-exclusive categories: surveillance/workup (n=78, 50%), BM-directed treatment (n=101, 64%) and GOC discussion (n=7, 4%). MTBm recommendations were fully followed in 113 cases (72%), partially in 13(8%), and not followed in 25(16%). Of the 38 patients whose recommendations were partially/not followed, the main reason was transition to hospice/death (n=26, 68%). Of the 101 patients recommended treatment, 68% (n=68) fully followed it, yet 31% (n=21) of them died within 3 months; for those living longer than 3 months (n=47, 69%), median KPS at 3 months was 70 (range 30-90). Of the entire cohort (n=157), only 20 (13%) established consistent PC follow-up (&amp;gt;1 outpatient visit) and 69 cases (44%) transitioned to hospice/died within 6 months, 30 of which (43%) still completed surgery (n=6) or radiotherapy (n=24) within this period. CONCLUSION Periodic assessment of MTBm recommendations is relevant for sensible BM management. Balancing treatment while focusing on QoL in a patient population with limited survival is challenging. PC assessment at MTBm could close this gap.

Control of major citrus postharvest diseases by sulfur-containing food additives

Sodium metabisulfite (SMBS), potassium metabisulfite (PMBS), aluminum sulfate (AlS) and aluminum potassium sulfate (AlPS), common sulfur-containing salts used as food additives, were evaluated for their antifungal activity against Penicillium digitatum, Penicillium italicum and Geotrichum citri-aurantii, the most economically important pathogens causing postharvest diseases of citrus fruits. In vitro radial mycelial growth was measured on potato dextrose agar (PDA) Petri dishes amended with five different concentrations of the salts (10, 20, 30, 50, 100 mM) after 7 d of incubation at 25 °C. SMBS and PMBS at all concentrations, and AIS and AIPS above 20 mM, completely inhibited the growth of these fungi. The curative antifungal activity of the four salts to control citrus green (GM) and blue (BM) molds and sour rot (SR) was evaluated on ‘Valencia’ oranges artificially inoculated in rind wounds with P. digitatum, P. italicum and G. citri-aurantii, respectively. In vivo primary screenings showed no significant antifungal activity of AlS and AlPS to control the three diseases at any dose tested, but SMBS and PMBS reduced the incidence and severity of GM, BM and SR at various concentrations. Effective salts and concentrations were selected for in vivo dip treatments in small-scale trials. Dips at room temperature (20 °C) in SMBS and PMBS at 20 and 50 mM for 60 or 120 s significantly reduced the incidence and severity of GM and BM, with PMBS at 50 mM for 120 s the most effective treatment. Conversely, dips in SMBS and PMBS at 50 mM for 60 or 120 s did not reduce SR incidence and severity. SMBS and PMBS treatments are potentially new tools to be included in reduced-risk non-polluting strategies to control Penicillium diseases, but not SR, on citrus fruits.

P2.12-22 Risk Factors for BM Incidence in SCLC: A Predictive Model for SCLC Patients on Brain Metastasis

P2.12-22 Risk Factors for BM Incidence in SCLC: A Predictive Model for SCLC Patients on Brain Metastasis

P14.105 High incidence of brain metastases in lung cancer patients at the time of primary diagnosis

Abstract BACKGROUND Brain metastases (BM) affect 8%-10% of all cancer patients and 40% of patients with metastatic cancer. The majority of BM originate from lung cancer (40%-50%), breast cancer (15%-25%), and melanoma (5%-20%). Total incidence proportions percentage (IP %) of brain metastases was reported as 9.6% for all primary sites combined, and was highest for lung cancer (19.9%). The incidence of BM is believed to be increasing, likely resulting from longer patient survival due to more effective systemic therapies for the primary cancer and the increased use of neuroimaging in neurologically asymptomatic patients. MATERIAL AND METHODS Our aim was to determine incidence of brain metastases in lung cancer patients at the time of primary diagnosis on cohort of our regular clinical practice. Since September 2014 till December 2017 189 primarily diagnosed patients with suspected lung cancer were evaluated with brain MRI as obligatory part of diagnostic protocol at N.N. Blokhin Russian Cancer Research Center. MR imaging protocol included T1, T2-weighted images, FLAIR, DWI, VIBE (with contrast enhancement, slice thickness &lt;1.2 mm). According to diagnostic guidelines for lung cancer in Russia, all patients underwent chest CT scan with contrast enhancement, bronchoscopy, abdominal ultrasonography, ultrasonography of cervical lymph nodes (+ CT to evaluate detected abnormalities), bone scintigraphy with X-ray control of detected abnormalities, surgical removal (in case of T1-T2 tumor) or tumor biopsy to determine morphology. Additionally, all patients underwent Whole Body MR DWI, some patients received FDG-PET/CT scan. RESULTS Brain metastases were detected in 89 (48%) of 189 patients, while only 9 patients (10.1% of patients with brain metastases) had neurological deficits. Lesion sizes were as follows: 0.1–0.5 cm in 46 (51.7%) patients, 0.5–1.0 cm in 21 (23.6%) patients, 1.0–2.0 cm in 7 (7.9%) patients, 2.0–3.0 cm in 8 (9.0%) patients and &gt;3.0 in 7 (7.9% patients). The majority of patients (45 - 50.56%) had solitary metastases, 10 patients (11.24%) had two lesions and 34 (38.20 %) patients had three and more lesions. Metastatic disease most commonly affected frontal lobes - 45 (50.56%) patients, temporal lobes - 36 (40.45%) patients, parietal lobes - 22 (24.72%) patients, occipital lobes - 22 (24.72%), basal ganglia and brainstem - 18 (20.22%), - 3 (3.37%), cerebellum - 30 (33.71%) patients. Concerning morphology, in 80 of 89 brain metastases NSCLC was identified and in 9 patients SCLC was observed. CONCLUSION Very high incidence of brain metastases in lung cancer patients at the time of primary diagnosis in our study cohort may be explained by the use of precision brain MRI as an obligatory part of diagnostic protocol at the time of primary admission. We suggest including precision brain MRI in guidelines for primary diagnosis of lung cancer patients as an obligatory examination

Prophylactic cranial irradiation (PCI) in limited-disease small-cell lung cancer (LD-SCLC) patients with brain imaging.

e20010 Background: PCI is recommended for patients with LD-SCLC who have a good response to initial therapy. But this recommendation has been made based on studies in which brain imaging was not a standard component of initial staging or follow-up. The aim of this study was to evaluate the efficacy of PCI for LD-SCLC patients with brain MRI immediately before PCI administration. Methods: This single-center, retrospective study included patients with LD-SCLC who achieve a good response to initial therapy without BM confirmed by MRI between 09/2002 and 06/2015. Responses were classified as CR and PR, according to RECIST. We categorized these patients into three groups: C: patients who achieved CR and received PCI; P: patients who achieved PR and received PCI; N: patients who did not receive PCI, regardless of responses. We compared OS, progression free survival (PFS), and the cumulative incidence of BM at 3 years (3yBM) among these groups. Results: A total of 79 patients were included in this study. At baseline, age and PS differed significantly between C and N. In P, patients were also younger than N. Although there were no statistical significances in OS and PFS between C and N, differences in 3 years OS rate and median PFS were numerically large. The 3yBM in C revealed marginal significance compared with N. However, No differences were observed with OS, PFS, and 3yBM between P and N. Conclusions: PCI may not add clinical benefit to LD-SCLC patients who did not achieve CR after initial therapy if absence of BM could be confirmed by MRI immediately before PCI administration. [Table: see text]

Abstract P1-12-08: The incidence and outcomes of brain metastases in HER2-positive metastatic breast cancer with the advent of modern anti-HER2 therapies

Abstract Background: Human epidermal growth factor receptor 2 (HER2) is over-expressed in approximately 20 - 30% of breast cancers. HER2-positive breast cancers frequently metastasize to the brain. In recent years, many new drugs have been approved for HER2-positive metastatic breast cancer (MBC). In the metastatic setting, trastuzumab was approved in 2000, lapatinib 2007, and pertuzumab and ado-trastuzumab emtansine in 2012. We sought to describe the incidence, time course, and prognostic factors of BM in patients (pts) with HER2+ MBC during the time when dramatic changes in systemic therapy occurred. Patients/methods: The study included pts with HER2-positive MBC treated at two academic hospitals: Dana Farber Cancer Institute (DFCI) (2000-2007 [DFCI-T1], 2008-2011 [DFCI-T2]) and University of North Carolina (UNC) (2012-2014). We examined the incidence of BM (at diagnosis [dx] and within 1-2 years of MBC dx). We combined the two cohorts to examine outcomes – time to BM, survival following MBC, and survival following BM – using the Kaplan Meier method and Cox regression modeling. Results: We identified 185 (DFCI n=128, 97 diagnosed 2000-2007 and 31 diagnosed 2008-2011; UNC n=57, all diagnosed 2012-2014) pts with HER2-positive MBC. Through a median of 4 years follow-up after the MBC dx (min 2, max 11), 118 had died and 67 were censored. The median age at MBC dx was 52 (min 25, max 88), 149 (82%) were Caucasian, 88 (48%) had hormone receptor (HR) positive BC, and 67 (37%) had de-novo (i.e., non-recurrent) MBC. BM was present at the MBC dx for 8% of pts in DFCI-T1, 16 % of pts in DFCI-T2, and 16% of pts at UNC. Within 1 year of the MBC dx, BM was present in 21% of DFCI-T1, 29% in DFCI-T2, 23% of UNC pts. Within 2 years of the MBC dx, 67 (36%) pts had developed BM, of which one third (22) were diagnosed at initial MBC presentation. In unadjusted analyses, there were no differences in time to BM dx by age (p=0.2), race (p=0.1) or HR status (p=0.1). The median survival following the development of BM for all pts was 1.5 years. A multivariable model predicting survival after the MBC dx, found factors associated with shorter survival included having (vs. not having) BM at the initial MBC dx, having received (vs. not having received) adjuvant HER2-directed therapy prior to the MBC dx, and having recurrent (vs. de novo) MBC (P≤0.02 for all). Age, HR status, race and time period of MBC dx were not significant in the multivariable model. Conclusions: Among pts diagnosed in the modern era, after new therapies became available, BM remains a common problem for pts with HER2-positive MBC. While no obvious trends in the incidence of HER2-positive MBC are suggested, conclusions regarding incidence trends should be considered hypothesis-generating until larger, population-based data become available. Nevertheless, a dx of BM early in the course of MBC treatment and prior receipt of adjuvant trastuzumab appeared to confer a more aggressive disease course. Coordinated, prospective collection of the incidence and outcomes of BM among pts with HER2-positive MBC, studies of pts who develop BM &amp;gt;2 years after their MBC dx, and clinical trials of treatment strategies for pts with trastuzumab-resistant BM are needed. Citation Format: Strulov Shachar S, Deal AM, Vaz-Luis I, Dees EC, Carey LA, Hassett MJ, Garrett AL, Benbow JM, Hughes ME, Mounsey L, Lin N, Anders CK. The incidence and outcomes of brain metastases in HER2-positive metastatic breast cancer with the advent of modern anti-HER2 therapies [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-12-08.

Incidence and pattern of bone metastases at presentation in Indian carcinoma breast patients.

Breast cancer (BC) is the most common female cancer and frequently metastases to the bones. Breast cancer among Indian women occurs a decade earlier and more aggressive than the western population. Screening guidelines are based on western studies. The aim of our study is to assess the role of Technitium99m bone scan (TBS) in screening Indian EBC patients at presentation. We also looked at the pattern of BM in all stages of BC. Patients with BC who had TBS at presentation from January 2012 to September 2015 were included in the study. Bone metastases were seen in 23.42% (241/1029). Of these, 10.06% (31/308) EBC, 25.60% (169/660) locally advanced BC (LABC) and 63.93% (39/61) of metastatic BC (MBC) patients had BM. Most common sites of BM were spine and pelvis. In long bone and sternum, proximal part was commonly involved. The incidence of BM in Indian BC patients at presentation is higher than western population. The incidence of BM per stage is similar to west. So TBS should be done in LABC and symptomatic EBC. There is high incidence of BM to spine and pelvis. In pelvis, SI joints and ilium and in long bones and sternum, proximal parts were commonly involved.

INFLUENCE OF PARABEN CONCENTRATION ON THE DEVELOPMENT OF GREEN AND BLUE MOLDS ON 'VALENCIA' ORANGE FRUIT

Three paraben sodium salts (p-hydroxy-benzoate) were evaluated as postharvest treatments to control citrus green (GM) and blue (BM) mold, caused by Penicillium digitatum and Penicillium italicum, respectively. The curative activity of sodium methyl (SMP; at 0.1, 1, 10, 40, 70, 100, 150, 200 and 250 mM), ethyl (SEP; at 0.1, 1, 10, 20, 30, 40, 70, and 100 mM) and propyl (SPP; at 0.1, 1, 4, 7, 10, and 100 mM) paraben were evaluated on ‘Valencia’ oranges by inoculating the pathogens in rind wounds and, about 24 h later, placing a drop of the solutions in the same rind wound. Disease development was assessed on fruit incubated at 20°C for 6 days. All three paraben salts reduced mold development. Concentrations of 150, 200 and 250 mM of SMP were the most effective and completely controlled both diseases. Concentrations of 20, 30, 40, 70 and 100 mM of SEP reduced the incidence of GM and BM by 100, 94, 100, 100 and 73% and 87, 62, 93, 100 and 80%, respectively. Concentrations of 7, 10 and 100 mM of SPP reduced the incidence of GM and BM by 94, 89 and 94% and 70, 88 and 100%, respectively. Most of these concentrations of SMP, SEP and SPP also significantly reduced the severity of GM and BM. SMP at 200 mM, SEP at 70 mM and SPP at 100 mM were, among the range of concentrations tested, selected as the best to be used in further research.

Epidermal Growth Factor Receptor (EGFR)-Mediated Adverse Events (AEs) in Patients (pts) With EGFR-Mutation Positive (EGFR M+) Non-Small Cell Lung Cancer (NSCLC) Treated With Afatinib (A): Metastatic Non-Small Cell Lung Cancer

performance status, T and N stage, number of metastatic lesions, and EGFR mutation type were included in univariate analysis (UVA). Candidate factors on UVAwere incorporated into a multivariate analysis (MVA) to identify factors independently associated with BMFS. Results: Of 112 patients, 33 (29%) were male, median age at diagnosis was 60 years, and 35 (31%) had a history of smoking. Seventy-three (65%) and 34 (30%) carried exon 19 deletions and exon 21 (L858R) mutations, respectively; 5 patients had other mutations. In total, 38 patients developed BM, for a crude incidence of 33.9%. Median survival was 25.2 months, and among patients with BM, the median time to BM was 28.9 months. The cumulative incidence of BM at 2 and 3 years was 14.7% and 30.3%, respectively. On UVA, the only factor significantly associated with BM was L858R (exon 21) mutation (hazard ratio [HR] 1.93 vs exon 19 deletion, PZ.035). Older age was nonsignificantly associated with less BM (PZ.11). On MVA, L858R retained borderline significance (HR: 1.82, PZ.054). The cumulative incidence of BM at 2 years was 23.2% in the exon 21 group vs 10.4% in the exon 19 group. Conclusion: Brain metastasis is a significant pattern of failure in EGFRmutant metastatic NSCLC patients maintained on erlotinib therapy, occurring in approximately a third of such patients. Contrary to previous reports, we found that patients with L858R mutations may be at particularly greater risk of BM compared to patients with exon 19 mutations. These results suggest a potential role for PCI in this select group of patients as a means of improving CNS-progression free survival. Author Disclosure: S. Patel: None. A. Rimner: E. Research Grant; Varian Medical Systems. G. Consultant; General Electric. A. Foster: None. Z. Zhang: None. K.M. Woo: None. H.A. Yu: None. G.J. Riely: None. A.J. Wu: G. Consultant; Pfizer, Inc.

Antifungal activity of sodium propylparaben alone or in combination with low doses of imazalil against Penicillium decay on citrus fruit

The performance of postharvest treatments with sodium propylparaben (SPP), alone or combined with low doses of the fungicide imazalil (IMZ), against citrus green (GM) and blue (BM) molds was evaluated on several citrus species and cultivars artificially inoculated with Penicillium digitatum and P. italicum, respectively, and incubated at 20 °C or cold-stored at 5 °C. Effectiveness of 100 mM SPP dips at 20 °C for 60 s was higher on oranges than on mandarins, with GM and BM incidence reductions of up to 60–90 % after 7 days at 20 °C. Irrespective of citrus cultivar and storage condition, SPP generally improved the curative action of 25 μl l−1 IMZ to control Penicillium molds. In additional tests, 100 mM SPP dips at 20 °C for 60 s only prevented GM on ‘Valencia’ oranges inoculated 24 h after treatment when combined with IMZ. It can be concluded that postharvest SPP treatments show promise as an effective alternative to be considered in citrus postharvest disease control programs.