Single Modality Therapy Research Articles

Polydopamine Coated PB-MnO2 Nanoparticles as an Oxygen Generator Nanosystem for Imaging-Guided Single-NIR-Laser Triggered Synergistic Photodynamic/Photothermal Therapy.

Exploring a combined phototherapeutic strategy to overcome the limitations of a single mode therapy and inducing high anticancer efficiency is highly promising for precision cancer nanomedicine. However, a single-wavelength laser activates dual photothermal/photodynamic therapy (PTT/PDT) treatment is still a formidable challenge. Herein, we strategically design and fabricate a multifunctional theranostic nanosystem based on chlorin e6-functionalized polydopamine (PDA) coated prussian blue/manganese dioxide nanoparticles (PB-MnO2@PDA-Ce6 NPs). Interestingly, the obtained PB-MnO2@PDA NPs not only offer an effective delivery system for Ce6 but also provide strong optical absorption in the near-infrared range, endowing high antitumor efficacy of PTT. More importantly, the as-prepared PB-MnO2@PDA-Ce6 nanoagents exhibit an effective oxygen generation, superior reactive oxygen species (ROS), and outstanding photothermal conversion ability to greatly improve PTT and PDT treatments. As a result, both in vitro and in vivo treatments guided by MR imaging on liver cancer cells reveal the complete cell/tumor eradication under a single wavelength of 660 nm laser irradiation, implying the simultaneous synergistic PDT/PTT effects triggered by PB-MnO2@PDA-Ce6 nanoplatform, which are much higher than individual treatment. Taken together, our phototherapeutic nanoagents exhibit an excellent therapeutic performance, which may act as a nanoplatform to find safe and clinically translatable routes to accelerate cancer therapeutics.

Dual-engineered, “Trojanized” macrophages bio-modally eradicate tumors through biologically and photothermally deconstructing cancer cells in an on-demand, NIR-commanded, self-explosive manner

To engineer tumor-tropic cells as drug delivery vehicles is a promising strategy to improve therapeutic specificity and efficacy for cancer treatment. However, conventional genetically engineered cell-based drug delivery systems are often capable of initiating single-mode therapy, and lack precise spatiotemporal control over the release of therapeutic payloads at tumor local, thus possibly causing severe systemic toxicity. Here, the macrophages are genetically engineered to encode a non-secreted form of EGFP-TNFα fusion protein and intracellularly carry near-infrared (NIR)-responsive heat-nanogenerators (HIMs). Owing to macrophages' intrinsic tumor tropism and HIMs’ photo-responsiveness to NIR, these macrophages (HIMs@eMET) can actively accumulate at tumor sites and undergo controlled photothermolysis induced by NIR-induced HIMs-mediated photothermal effects (PTE). Such heat-induced cell explosion enables spatiotemporally controlled release of non-secreted TNFα from macrophages and effectively kills cancer cells. Importantly, in a preclinical tumor model, HIMs@eMET actively migrate to tumors where PTE and released EGFP-TNFα exhibit an enhanced antitumor effect, suppressing tumor growth and significantly prolonging animal survival without eliciting adverse side effects. Thus, this study demonstrates the potential of such dual-engineered macrophages in bi-modal cancer therapy.

Predictors of chemoradiotherapy versus single modality therapy and overall survival among patients with unresectable, stage III non-small cell lung cancer.

Concurrent chemoradiotherapy (cCRT) was the standard of care for patients with unresectable stage III non-small cell lung cancer (NSCLC) prior to the PACIFIC trial, however, patients also received single modality therapy. This study identified predictors of therapy and differences in overall survival (OS). This retrospective study included stage III NSCLC patients aged ≥65 years, with ≥1 claim for systemic therapy (ST) or radiotherapy (RT) within 90 days of diagnosis, identified in SEER-Medicare data (2009-2014). Patients who had overlapping claims for chemotherapy and RT ≤90 days from start of therapy were classified as having received cCRT. Patients who received sequential CRT or surgical resection of tumor were excluded. Predictors of cCRT were analyzed using logistic regression. OS was compared between therapies using adjusted Cox proportional hazards models. Of 3,799 patients identified, 21.7% received ST; 26.3% received RT; and 52.0% received cCRT. cCRT patients tended to be younger (p <0.001), White (p = 0.002), and have a good predicted performance status (p<0.001). Patients who saw all three specialist types (medical oncologist, radiation oncologist, and surgeon) had increased odds of receiving cCRT (p<0.001). ST and RT patients had higher mortality risk versus cCRT patients (hazard ratio [95% CI]: ST: 1.38 [1.26-1.51]; RT: 1.75 [1.61, 1.91]); p<0.001). Several factors contributed to treatment selection, including patient age and health status, and whether the patient received multidisciplinary care. Given the survival benefit of receiving cCRT over single-modality therapy, physicians should discuss treatment within a multidisciplinary team, and be encouraged to pursue cCRT for patients with unresectable stage III NSCLC.

Ability of the combined clinical cell-cycle risk score to identify patients that benefit from multi versus single modality therapy in NCCN intermediate and high-risk prostate cancer.

346 Background: Prolaris combines RNA expression analysis of cell cycle progression genes with clinicopathologic information to create a combined clinical cell-cycle risk score (CCR). We evaluated the ability of CCR to predict metastasis (mets) in men for whom guidelines indicate that multimodality therapy (MTx) should be considered. Methods: A commercial cohort (N=15669) of National Comprehensive Cancer Network unfavorable intermediate-risk (UFI) and high-risk (HR) men revealed a distribution of 70.5% and 29.5% respectively. A CCR threshold of 2.112 was selected so that 29.5% of these men were above the threshold. MTx was defined as combined use of androgen deprivation therapy with radiation (RT) or surgery, or with adjuvant RT. Associations were evaluated in a 718-person retrospective, multi-institutional database of Prolaris-tested UFI and HR men. Kaplan-Meier (KM) analyses and Cox regressions were used to estimate the effects of prognostic covariates. Results: Median follow-up was 5.13 years. CCR predicted mets in the full cohort (HR =3.8 [2.7,5.2], p&lt;10−15) and after accounting for CAPRA (HR=4.3 [2.7,7.0], p&lt; 10−7). CCR also was a significant predictor of mets in patients who received STx, as a continuous predictor (HR=4.0 [2.6,6.1], p&lt;10−9) and when dichotomized at the threshold (HR=15.9 [5.4,46.5], p&lt; 10−9). The KM probability of mets by 10 years for those below and above the threshold was 4.3% and 20.4% respectively. MTx reduced patients’ risk of mets (HR=0.46 [0.22,0.97], p=0.04), and treatment benefit can be evaluated as a function of CCR score (Table). Conclusions: The CCR score prognosticates a clinically meaningful different risk of metastasis for those receiving MTx versus STx. Approximately 27% and 73% of people with HR or UFI risk cancer have CCR scores below the risk threshold and may consider STx after considering the difference in risk of mets.[Table: see text]

Reduced Graphene Oxide/Mesoporous Silica Nanocarriers for pH-Triggered Drug Release and Photothermal Therapy.

A sandwich structured bifunctional nanocarrier (rGO@msilica) composed of an inner layer of reduced graphene oxide (rGO) and an outer layer of mesoporous silica (msilica) was developed for synergistic chemo-photothermal therapy. The rGO@msilica not only acted as a pH-triggered drug nanocarrier but also worked as a near-infrared (NIR) photothermal agent. The loaded drug, doxorubicin (DOX), in the rGO@msilica nanocarrier was controllably released in the acidic tumor microenvironment. Moreover, the cancer cells were ablated by laser irradiation (808 nm), contributing to the high photothermal conversion efficiency of the rGO core. With this two-in-one system, in vitro cancer cell experiments indicated that the synergistic therapeutic strategy was superior to those of single modality therapy. These findings imply that the bifunctional rGO@msilica nanocarrier could provide a powerful platform for cancer therapy.

Radiation as a single modality treatment in localized pancreatic cancer.

703 Background: Locally advanced pancreatic cancer (LAPC) is managed with multimodality therapy. A subset of patients with LAPC are not good candidates for aggressive treatment. The aim here is to evaluate the outcomes of single modality radiation therapy for LAPC using the National Cancer Database (NCDB). Methods: Data was obtained between years 2004 and 2013. Pancreatic ductal adenocarcinoma (PDAC) patients with unresectable local disease were identified excluding patients who received chemotherapy or surgery. Univariate and multivariable analyses identified factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used for patient characteristics and overall survival (OS). Results: A total of 6,590 patients were included; 480 (6.9%) received radiation therapy only and 6470 (93.1%) received no treatment. Mean age was 73.5 (range, 28‐90) years, with the majority being White (N = 5685; 83.2%) and female (N = 3779; 54.4%). Poorly differentiated histology and tumors ≥ 4 cm ( &gt; T3 stage) accounted for 47.8% and 52.7%, respectively. The median dose of radiation was 39.6 Gy. Stereotactic body radiation (SBRT) was given in 64 patients and external-beam/Intensity modulated radiotherapy (IMRT) in 416 patients. Charlson-Deyo score of +1 was seen in 34.4% of patients who received no treatment, 32.8% of patients who received SBRT and in 29.8% of patients who received external-beam IMRT. Radiation therapy was associated with improved OS compared to no treatment in univariate and multivariable analyses controlling for sex, Charlson-Deyo score, age, tumor size, amongst other covariates. Median OS for patients who received SBRT, external-beam/IMRT or no radiation was 8.6, 6.7 and 3.4 months; respectively (P &lt; 0.001). There is a significant difference in 12-month OS for the SBRT cohort (31.9%; 95% CI 20.9%-43.5%) compared to patients who received no radiation (15.1%; 95% CI 14.2%-16.0%), similarly seen on multivariable analysis (HR 0.50; 95% CI 0.38-0.65; P &lt; 0.001). Conclusions: The current study is the first to evaluate the efficacy of radiation as single modality therapy in LAPC. The results suggest a potential benefit for radiation therapy alone, in comparison to no treatment.

Self-Assembly Nanoparticles for Overcoming Multidrug Resistance and Imaging-Guided Chemo-Photothermal Synergistic Cancer Therapy.

Background and PurposeThe development of multiple drug resistance (MDR) to chemotherapy and single modal therapy remains unsatisfied for the eradication of tumor, which are major obstacles in cancer therapy. This novel system with excellent characteristics for inhibition of P-glycoprotein (P-gp), and for near-infrared fluorescence (NIRF) imaging-guided chemo-photothermal therapy (PTT), has been identified as a promising way to MDR and achieve synergistic cancer therapy.MethodsIn this study, we successfully synthesized a multifunctional theranostic system, which was developed through FDA-approved self-assembling drugs, which contain anticancer drug doxorubicin (Dox), imaging and high photothermal conversion drug indocyanine green (ICG) and P-gp regulator TPGS (the system named T/Dox-ICG). We studied the characterization of T/Dox-ICG NPs, including the TEM, SEM, DLS, UV-vis-NIR, zeta potential, CLSM, in vitro FL imaging, in vitro photothermal effect, in vitro Dox and ICG release. We used CLSM to verify the location of intracellular distribution of Dox in SCG 7901/VCR cells, Western blot was performed to demonstrate the TPGS-mediated inhibition of P-gp. And, the cytotoxicity of materials against SCG 7901/VCR cells was studied by the MTT assay.ResultsThe TEM showed the T/Dox-ICG NPs had good monodispersity with diameters of 19.03 nm, Dox and ICG could be released constantly from T/Dox-ICG NPs in vitro. In vitro cell experiments demonstrated higher Dox accumulation and retention in the nucleus. Western blot showed TPGS could obviously inhibit the expression of P-gp. In vitro cytotoxicity assay showed more significant cytotoxicity on MDR cells (SCG 7901/VCR) with only 8.75% of cells surviving.ConclusionMDR cancer therapy indicates that it may be important to develop a safer system that can simultaneously inhibit the drug transporters and monitor the delivery of chemotherapeutic agents, and combination therapy have raised widespread concern on tumor treatment.

Role of surgery in oligometastatic prostate cancer.

Androgen deprivation therapy as single modality therapy was the standard management for oligometastatic prostate cancer (PCa). Current paradigm shifts toward a multimodality therapy approach, targeting all sites of disease, including treatment of the primary in the form of radical prostatectomy or radiation therapy. The objective of this article was to reveiw the literature regarding the role of surgery in oligometastatic PCa. PubMed and MEDLINE electronic databases were queried for English language articles from January 1, 1980 to March 31, 2019. Keywords use included oligometastatic PCa, metastatic prostate cancer (mPCa), radical prostatectomy, and cytoreductive prostatectomy. Preclinical, prospective, and retrospective studies were included. There is no published randomized controlled trials, evaluating the role of surgery in mPCa. Preclinical and retrospective data suggest benefit of primary tumor treatment in mPCa. Current literature supports the concept of cytoreductive surgery as it can prevent late symptomatic local progression, has acceptable complications, and may prolong survival in patients with mPCa. Surgery is a feasible procedure in mPCa which may improve outcome in mPCa. However, there is no Level 1 evidence, yet that support the role of surgery in mPCa. The results from well-organized prospective, randomized controlled trials are awaited before performing radical prostatectomy for mPCa in clinical practice.

Palliative Treatment Utilization and Outcomes in Elderly Patients with Locally Advanced Esophageal Carcinoma: A Review of the National Cancer Database

A significant percentage of elderly patients with locally advanced esophageal cancer receive non-definitive treatment. The goal of this study was to further examine palliative treatment choices and outcomes in this group. Patients ≥70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2013 who received palliative therapy were identified using the National Cancer Database and stratified based on treatment type: chemotherapy only, radiation only, or sequential chemoradiation. Sequential treatment was defined as chemotherapy and radiation start dates ≥14 days apart. Variables associated with choice of treatment modality were evaluated using logistic regression and survival was evaluated using Cox proportional hazard analysis. 3,422 patients were identified with a median age of 79. Patients were predominantly white (87.0%) and male (69.4%), with tumors in the distal esophagus (56.4%) and of adenocarcinoma histology (51.5%). Overall, 16.5% of patients received chemotherapy only, 51.0% received radiation only, and 31.6% received sequential chemoradiation. The median overall survival was 8.1 months for radiation therapy (95% CI: 7.6-8.6); 9.9 months for chemotherapy (95% CI: 8.6-11.1); and 16.1 months for sequential treatment (95% CI: 14.7-17.5). Radiation dose ≤30 Gy was more common within the radiation alone group (24.7% vs 8.0% of sequential group). Sequential chemoradiation demonstrated improved survival over single-modality therapy regardless of histology (p<.001). For adenocarcinoma, chemotherapy alone resulted in improved survival over radiation alone (p = .001), however no difference was observed between these treatments for squamous cell carcinoma (p = 0.09). Age (hazards ratio (HR) 1.10, 95% CI: 1.01 - 1.22) and high tumor grade (HR 1.35, 95% CI: 1.24 - 1.46) were associated with an increase in mortality. Treatment at an academic center (HR 0.91, 95% CI: 0.83 - 0.99) and sequential treatment (HR 0.66, 95% CI: 0.58 - 0.75) were associated with decreased mortality. Higher income (Odds ratio (OR) 1.88, 95% CI: 1.34 to 2.63) and educational status (OR 1.34, 95% CI: 1.06 to 1.69) were associated with increased likelihood of receiving sequential treatment versus chemotherapy alone, whereas clinical stage III (OR 0.73, 95% CI: 0.58 to 0.91) and adenocarcinoma histology (OR 0.72, 95% CI: 0.57 to 0.91) were associated with an increased likelihood of receiving chemotherapy only. Sequential chemoradiation was associated with improved survival when compared to single modality treatment. Chemotherapy alone demonstrated improved outcomes over radiation alone for adenocarcinoma, however these treatments demonstrated comparable survival for squamous cell carcinoma. A limitation of this study is the inability to account for selection factors such as performance status or assess important outcomes such as quality of life that also impact palliative treatment decisions and survival.

Bismuth particles imbedded degradable nanohydrogel prepared by one-step method for tumor dual-mode imaging and chemo-photothermal combined therapy

In this work, bismuth imbedded nanohydrogel (Bi@CMC) was synthesized with ultra-violet irradiation. A series of characterizations showed that the size of Bi@CMC was about 35–80 nm, while the imbedded bismuth particles were about 5 nm. The Bi@CMC had good stability and dispersibility, and the photothermal conversion efficiency was up to 40.21%. Methyl thiazolyl tetrazolium results showed that over 68% of the cells survived when the probe concentration reached 2 mg/mL, showing low toxicity of Bi@CMC. After the adsorption of doxorubicin, a multi-functional nanoprobe (DOX/Bi@CMC) integrating computed tomography/photoacoustic dual-mode imaging and photothermal/drug dual-mode therapy was obtained. DOX/Bi@CMC could be enriched at the tumor site through enhanced permeability and retention effect. After irradiation with near-infrared region laser, the probe could not only generate heat effect, but also thoroughly released drug through nano-hydrogel disintegration, thus achieving the purpose of chemo-photothermal combined therapy. The therapeutic effect was significantly better than that of the single mode therapy. It was also found that the probe size decreased sharply after nano-hydrogel’s disintegration, indicating that it would be metabolized more easily, and therefore, could effectively reduce the side effect and toxicity. Hematoxylin and eosin staining of main organs and blood biochemical indicators showed that the probe had good biological safety after injection. The current work proposes a new dual-mode bio-imaging and chemo-photothermal combined therapy nanoprobe, which presents good application prospects for tumor theranostic.

Factors associated with receipt and overall survival of concurrent chemoradiotherapy versus single modality therapy in unresectable stage III NSCLC.

e18191 Background: While concurrent chemoradiotherapy (cCRT) is standard of care for patients (pts) with unresectable stage III non-small cell lung cancer (NSCLC), some pts receive single modality therapy. This study identified predictors of therapy and differences in overall survival (OS) in a Medicare population. Methods: This retrospective study used Surveillance, Epidemiology and End Results -Medicare data (2009-2014). Stage III NSCLC pts aged ≥65 yrs, with ≥1 claim for systemic therapy or radiotherapy (RT) within 90 days of diagnosis were included. cCRT pts had overlapping claims for chemotherapy and RT ≤90 days from start of therapy; remaining pts were grouped by first therapy received. Sequential CRT patients and those with surgical resection of tumor were excluded from this analysis. Logistic regression was used to analyze predictors of cCRT. Multivariable Cox proportional hazards models were used to compare OS between therapies. Results: Of 4,544 pts identified, 51% received cCRT, 21% systemic therapy, and 27% RT. Across groups, cCRT patients were likely younger (p &lt; 0.001), White (p &lt; 0.001), male (p = 0.015), and with a good predicted performance status (PS) (p &lt; 0.001). After adjustment, several variables were predictive of receiving cCRT (Table). Median OS was 14.7 months (mo) for cCRT vs. 10.9 mo for systemic therapy (adjusted hazard ratio [HR]: 1.36, 95% CI: 1.24-1.49, p &lt; 0.001) vs. 7.8 mo for RT (adjusted HR: 1.55, 95% CI: 1.42-1.69, p &lt; 0.001). Conclusions: Only 51% of pts received cCRT. Age, race, stage, PS and comorbidity index were predictive of cCRT. Given the survival benefit, physicians should be encouraged to pursue cCRT in all eligible pts. Further efforts to develop less morbid therapies are critical in this population. [Table: see text]

Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma

AbstractRadiation fields for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have shrunk over time; involved-site radiation therapy (ISRT) has replaced extended-field radiation therapy (EFRT) and involved-field radiation therapy (IFRT), but this has not been validated. The role of systemic therapy is unclear. We reviewed 71 stage I/II NLPHL patients and assessed progression-free survival (PFS), overall survival (OS), locoregional disease-free survival, and distant disease-free survival (DDFS). Median patient age was 39 years, and 61% had stage II disease. Thirty-six (51%) received radiation therapy (RT) only, 6 (8%) received systemic therapy only, and 29 (41%) received both. More patients receiving combined therapy had B symptoms (P = .035) and stage II disease (P = .001). In the RT-only group, 9 (25%) received EFRT, 13 (36%) received IFRT, and 14 (39%) received ISRT; in the combined-modality group, 3 (10%) received EFRT, 7 (24%) received IFRT, and 19 (66%) received ISRT. After a median follow-up of 6.2 years, 15 patients relapsed (13 distant, 2 locoregional). Five-year PFS and OS rates were 86% and 96% and did not differ by treatment. In the RT-only group, follow-up was shorter in the ISRT cohort (2.6 years vs 17.9 years [EFRT] and 8.5 years [IFRT], P < .01), but 5-year PFS did not differ by field size (P = .20). Locoregional control rates were 100% for the RT-only and combined groups, and corresponding 5-year DDFS rates were 93% and 95% (P = .95). Eight patients (11%) experienced a second malignancy (1 within RT field). Six patients died (1 from lymphoma). Use of limited ISRT fields does not appear to increase the risk of locoregional relapse, even when RT is given as single-modality therapy.

Local Photothermal/Photodynamic Synergistic Therapy by Disrupting Bacterial Membrane To Accelerate Reactive Oxygen Species Permeation and Protein Leakage.

Bacterial infection is still a ticklish clinical challenge even though some advanced antibacterial materials and techniques have been put forward. This work reports that rapid and effective antibacterial performance is achieved by the synergistic local photothermal and photodynamic therapy (PTDT). Within 10 min of light irradiation, both Escherichia coli and Staphylococcus aureus are almost completely eliminated by the action of photothermy (52.1 °C) and limited reactive oxygen species (ROS), the corresponding bacterial killing efficiencies are 99.91 and 99.97%, respectively, which are far higher than single modal therapy, i.e., photothermal therapy or photodynamic therapy with antibacterial efficacy of 50 or 70%, respectively. The mechanism is that bacterial membrane permeation is increased by PTDT because photothermy shows more severe impact only on E. coli by destroying the outmost bacterial panniculus, whereas the inner panniculus of the two kinds of bacteria is more sensitive to ROS. Hence, ROS penetrates the bacterial membrane more easily, and meanwhile, the proteins in the bacteria are severely lost after the bacterial membrane disruption, which leads to bacterial death. In vivo results reveal that rapid and effective sterilization is an important process to accelerate wound healing, and the traumas on the rats' backbones heal well within 12 days by PTDT. Furthermore, the PTDT is friendly to major organs of rats during the therapeutic process. Therefore, the synergistic therapy system can be a safe therapeutic system for clinical sterilization with great potential. More importantly, the antibacterial mechanism presented in this work has great guiding significance for the design of other advanced antibacterial systems and techniques.

Clinical Factors Associated With Cost in Head and Neck Cancer: Implications for a Bundled Payment Model.

To determine which factors influence cost in head and neck cancer (HNC) to inform the development of a bundled payment model (BPM). Patients with stages 0 to IVB (by American Joint Commission on Cancer, 7th edition) HNC of various sites and histology treated definitively at a single tertiary care center during 2013 were included. Clinical variables and direct cost data were obtained, and their associations were investigated using χ2, t, Wilcoxon rank sum, and analysis of variance testing. Results were used to develop a BPM. One hundred fifty patients were included; 87% were white, 74% were men, 48% had oropharyngeal cancer, and 58% had stage IVA disease. Treatment consisted of surgery alone (17%), radiation alone (11%), surgery plus radiation (14%), chemoradiation (45%), and surgery plus chemoradiation (13%). On multivariable analysis, both increasing group stage and number of treatment modalities used were significantly associated with higher cost. Given that stage often dictates treatment, we developed three cost tiers that were based on overall treatment modality. Tier A, the least costly, consisted of single-modality therapy with either surgery alone or radiation alone (median cost divided by the median overall cost of treatment, 0.54; 25th to 75th percentile range, 0.29 to 1.02), followed by tier B, which consisted of bimodality therapy with either chemoradiation or surgery plus radiation (1.03; range, 0.81 to 1.35), followed by tier C, which consisted of trimodality therapy with surgery plus chemoradiation (1.43; range, 1.10 to 1.96). The number of treatment modalities required is the primary driver of cost in HNC. These data can simplify development of a comprehensive HNC BPM.

What's Love Got to do with it? Marital status and survival of head and neck cancer.

To determine whether marital status independently predicts survival in a head and neck cancer (HNC) survivor population. In this retrospective cohort study, we analysed data from 460 adult patients (59.31±11.42) years diagnosed with HNC at an academic tertiary referral centre between 1997 and 2012. Cox proportional hazards model estimated the effect of marital status on survival. Our study had 73% men, and 82.2% were Whites. We found an association between marital status and HNC survival. Unmarried HNC patients had a 66% increase in hazard of death compared to married patients (aHR=1.66, 95% CI=1.23-2.23). This was after controlling for sociodemographic variables (age, race, sex and health insurance status), social habits (tobacco and alcohol), primary anatomical subsite (oral cavity, oropharyngeal, laryngeal and others), stage at presentation (early vs. late stage) and treatment modality (surgery, surgery with adjuvant therapies, other single modality therapy and palliative care). Being married confers survival advantage for HNC survivors. Our finding underscores the need to recognise this aspect of survivorship. Social support should be considered part of standard care for managing HNC. There may also be need to develop other support mechanisms, especially for unmarried HNC survivors.

Polydopamine-Based Multifunctional Platform for Combined Photothermal Therapy, Chemotherapy, and Immunotherapy in Malignant Tumor Treatment.

We designed a multifunctional platform by coloading DOX, an antitumor drug, and imiquimod (R837), an immune adjuvant against Toll-like-receptor-7 (TLR-7), onto polydopamine nanoparticles (PDA NPs), a photothermal therapy (PTT) agent, to develop PDA/DOX&R837 NPs used as combined photothermal therapy, chemotherapy, and immunotherapy in order to enhance the cancer therapeutic effects. For a high delivery to malignant tumors, a folate ligand-receptor recognition molecule was grafted to the nanoparticle surface for a higher cellular uptake efficiency. The particle size, ζ potential, morphology, drug loading content, and drug release profiles of FA-PDA/DOX&R837 NPs were investigated. The antitumor effects under near-infrared (NIR) laser radiation were evaluated, and our results showed that a three-mode strategy combined therapy was significantly superior to single-mode therapy for tumor suppression. The synergetic toxicity of hyperthermia and DOX almost completely eliminated tumors, and together with R837, they further promoted the maturation of dendritic cells to induce a strong antitumor immune response, making tumor recurrence substantially lower than that without R837. This platform can be used as a potential targeted drug delivery system for combined cancer therapy.

Quality of Life Within the First 6 Months of Vestibular Schwannoma Diagnosis With Implications for Patient Counseling.

To evaluate quality-of-life (QOL) in patients with sporadic vestibular schwannoma (VS) with particular focus on those recently diagnosed. Cross-sectional survey, Penn Acoustic Neuroma Quality of Life (PANQOL) instrument. Acoustic Neuroma Association and a single tertiary referral center. Patients with sporadic VS. Domain-specific and total PANQOL scores comparing treatment modalities after adjusting for baseline covariates of interest. Among all 1,288 respondents there were 229 (18%) who were recently diagnosed and had not yet selected a treatment modality, 303 (24%) who were observed, 185 (14%) who underwent radiosurgery alone, 507 (39%) who underwent microsurgery alone, and 64 (5%) who underwent radiosurgery and microsurgery. After adjusting for covariates of interest, total PANQOL scores were highest for the observation cohort (65; 95% CI 62-68), lowest for patients treated with multimodality therapy (56; 51-61) and those recently diagnosed (58; 55-62), and intermediate for those who received microsurgery alone (60; 58-62) and radiosurgery alone (61; 57-64) (global comparison, p = 0.001). When comparing groups that received single-modality therapy, there were no statistically significant differences in total PANQOL scores at short (0-5 yr), intermediate (6-10 yr), or long-term (≥11 yr) follow-up after adjusting for baseline covariates (all, p > 0.05). A new diagnosis of VS frequently imparts significant anxiety on the patient and leads to a temporary reduction in QOL. Notably, anxiety domain QOL scores among patients with newly diagnosed VS are poorer than patients who have observed their tumor for 6 months or longer. When feasible, an initial period of observation may afford patients valuable time to reconcile with the new diagnosis, to learn more about treatment options, and to discover whether there is tumor growth. In turn, this valuable information can be used to inform sound decision-making regarding tumor management.

PEGylated hydrazided gold nanorods for pH-triggered chemo/photodynamic/photothermal triple therapy of breast cancer

Integration of multimodal therapies into one nanoplatform holds great promise to overcome the drawbacks of conventional single-modal therapy and pursues enhanced anticancer efficacy. Herein, we developed a PEGylated gold nanorods (GNRs)-based nanoplatform (GNRs-MPH-ALA/DOX-PEG) with pH-responsive drug release property for triple-combined chemotherapy (CT), photodynamic therapy (PDT) and photothermal therapy (PTT) of breast cancer. GNRs were first decorated with mercaptopropionylhydrazide (MPH) and thiol-terminated monomethoxyl poly(ethylene glycol) (mPEG-SH) via Au-thiol linkage, and subsequently conjugated with chemotherapeutant doxorubicin (DOX) and pro-photosensitizer 5-aminolevulinic acid (ALA) through acid-liable hydrazone bonds between drugs and MPH molecules. The resulting nanoplatform GNRs-MPH-ALA/DOX-PEG exhibited excellent stability in physiological solutions and pH-responsive DOX and ALA release behaviors. In vitro studies showed that GNRs-MPH-ALA/DOX-PEG could efficiently enter human breast cancer MCF-7 cells and release DOX and ALA into cytoplasm. Furthermore, DOX could locate in the cell nucleus and ALA was productively metabolized into protoporphyrin IX (PpIX). Upon near-infrared (NIR) irradiation, PpIX produced enough reactive oxygen species for PDT and meanwhile GNRs could efficiently induce hyperthermia for PTT. Compared with single CT and dual-modal CT/PDT or CT/PTT treatment, the triple-combined CT/PDT/PTT treatment could more efficiently kill MCF-7 cells via a superadditive antitumor effect. Furthermore, the circulation half-life of GNRs-MPH-ALA/DOX-PEG in the blood was as long as approximately 52 min and it exhibited a tumor accumulation of 3.3%. The triple-combined CT/PDT/PTT treatment could completely suppress tumor growth without obvious systemic toxicity. Our study paves a new avenue for multimodal therapy of breast cancer. Statement of significanceThe development of a simple but effective strategy to construct a versatile nanoplatform for multi-combined therapy still remains an enormous challenge. In this work, we developed a novel and simple nanoplatform GNRs-MPH-ALA/DOX-PEG with pH-responsive drug release for triple-combined chemotherapy (CT), photodynamic therapy (PDT) and photothermal therapy (PTT) of breast cancer. The nanoplatform could be efficiently internalized by MCF-7 cells. The intracellular GNRs-MPH-ALA/DOX-PEG could release DOX for CT, induce hyperthermia for PTT and generate high levels of ROS for PTT. Compared with single CT and dual-modal CT/PDT or CT/PTT treatments, the triple-combined CT/PDT/PTT treatment could more efficiently kill MCF-7 cells via a superadditive antitumor effect. Furthermore, upon triple-combined CT/PDT/PTT treatment, the tumor growth was completely suppressed without obvious systemic toxicity.

744P - Trends of care of non-metastatic pancreas cancer patients in Ireland

Background: Surgery offers the only chance of cure in non-metastatic pancreatic cancer. However, chemo- and radio-therapy also play important roles in pancreatic cancer care. How each of these different modalities of treatment impact on pancreatic cancer outcome is unclear. The National Cancer Registry (NCRI) is a publicly appointed body, established to collect and classify information on all cancer cases which occur in Ireland. We analysed these data with the objective to examine the trend of care of stage 1 to 3 pancreas cancer in Ireland. Methods: Pancreatic cancer data have been collected by NCRI since 1994. Only those with stage 1 – 3 adenocarcinoma of the pancreas (PDAC) were included in the final analyses. Descriptive statistics, Pearson chi-square test and survival analysis using Kaplan Meier curve with log-rank test and cox regression was performed. Results: Between Jan 1994 and Dec 2013, of the 8230 patients with pancreatic cancer identified from the NCRI database, 4298 pts had histologically proven adenocarcinoma. Among these, 1177/27% of patients (pts) had stage 1 – 3 disease. 52% were male and 74% of pts were over 60 years of age. Stage 1, 2 and 3 disease comprised 25%, 32% and 42% of pts respectively. Overall 48 % of pts had surgery, 44% had chemotherapy and 21% had radiotherapy. 364, 31% pts did not have any therapy at all. Compared to those who did not have any treatment, there was an incremental benefit in overall survival (OS) with the more number of different modalities of treatment involved (Table). OS was 3 mos with no treatment, 8 mos with either chemo or radiation (HR 0.57), 11 mos with chemo and radiation (HR 0.46), 18 mos with surgery only (HR 0.27) and 20 mos with surgery with chemo and/or radiation therapy (HR 0.24).Table: 744PNOSHRNo treatment364, 31%3 monthsMultimodality therapies including surgery287, 25%20 months0.24 (95% CI: 0.20 – 0.28)Surgery only245, 21%18 months0.27 (95% CI: 0.22 – 0.32)Multimodality therapy (no surgery)95, 8%11 months0.46 (95% CI: 0.36 – 0.58)Single modality therapy (no surgery)179, 16%8 months0.57 (95% CI: 0.48 – 0.69) Open table in a new tab Conclusions: Multimodality therapy with surgery improves OS in non-metastatic pancreatic cancer with incremental benefit seen from even single modality therapy. Legal entity responsible for the study: Rozana Abdul Rahman, Ray McDermott. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Treatment and Outcomes of Primary Urethra Cancer.

Urethral cancer is a rare malignancy, representing <1% of all malignancies. Optimal management, due to its rarity, presents as a treatment dilemma for physicians. There is a lack of consensus regarding treatment as large randomized trials cannot be performed; thus, optimal management decisions rely on study of retrospective cases. This is a review of our institutional experience with urethral cancer treated with various treatment modalities. A retrospective chart review was performed on 31 patients treated for primary cancer of the urethra from 1958 to 2008. The patients were stratified by sex, histologic type, stage, date of diagnosis, type of treatment, and last follow-up. Early stage cases were designated as Tis-T2N0M0 and advanced cases were designated as T3-4, N+ or M+. Analysis was performed based on clinical stage, treatment modalities and outcomes. Fourteen early stage cases and 17 advanced stage cases of urethral cancer were analyzed. The majority of early stage cases occurred in men (M:F=8:6) and the majority of advanced stage cases occurred in women (M:F=5:12). The most common histology was squamous cell carcinoma for both early and advanced stage cases. Surgery was the preferred modality of treatment for early stage cases (surgery used in 13 cases vs. chemo/radiotherapy used in 1 case) while for advanced cases, radiation ±chemotherapy was commonly used. Overall survival for this series was 45% at mean follow-up of 7 years. Eight of the 14 cases of early stage cancer remained disease free at last follow-up. Comparatively, only 5 of 17 with advanced cancers had no apparent disease at last follow-up. All but one of those patients were treated with combined modality therapy. Patients with early stage urethral cancers do well with single modality therapy, whereas patients who present with advanced cancers may benefit from combined modality therapy. More extensive study is required to recommend a particular treatment protocol. However, in this rare malignancy, institutional experiences provide the best evidence currently due to the lack of multi-institutional trials.