Single Treatment Modality Research Articles

Glioblastoma in the elderly: initial management.

Glioblastoma is the most common primary CNS malignancy and it is becoming more frequently diagnosed in the elderly population. Glioblastoma is associated with a dismal prognosis and remains a huge challenge for the neuro-oncology community. Surgical resection/biopsy is well defined as an important first approach in the care of this disease, for tumor diagnosis, molecular analysis and maximum resection. MGMT promoter methylation status has proved to be a useful indicator of whether single modality (RT or TMZ alone) or combined modality treatment may achieve better outcomes. Post-operative treatment options include: (I) hypofractionated radiotherapy (HRT) with concurrent and adjuvant temozolomide (TMZ) or (II) HRT alone (MGMT unmethylated patients); (III) TMZ alone (MGMT methylated patients) when combined modality is not feasible due to patient poor performance status or multiple comorbidities. Following the positive survival outcomes of the CCTG CE.6/EORTC 26062-22061 phase III trial which randomized newly diagnosed glioblastoma patients aged 65 or older to HRT (40 Gy/15 fractions) with concurrent and adjuvant temozolomide to HRT alone, combined modality therapy (CMT) with HRT with concurrent temozolomide as the initial post-surgical approach should be considered in patients well enough to have treatment. In meantime, future trials addressing new approaches are needed to improve outcomes in this fatal disease.

An Investigative Approach to Treatment Modalities for Squamous Cell Carcinoma of Skin.

Squamous cell carcinoma of skin has become an important matter of discussion worldwide due to high number of deaths. Treatment of such cancer involves use of drugs (chemotherapy) along with surgery or radiation therapy. The combination chemotherapy is preferred over single treatment modality may be due to synergistic effect of targeting agent resulting in reduced drug dose, reduced cytotoxic effect and improved efficacy and survival rate. The objective of this work is to provide insight into the squamous cell carcinoma of skin; the various approaches and challenges adapted to surmount the cancer malignancies. Research evidence shows that nanoparticle based therapeutic delivery to squamous cell carcinoma is equanimous to lead therapeutic approaches for intervention of cancer growth. Active chemotherapeutic approach is one of the leading therapies to such cancer cells due specific selectivity towards the EGFR-receptors over-expressed in tumor cells. Review of numerous research publications revealed innate toxicity of chemotherapeutic agents, and substantiated active receptor mediated drug targeting for therapeutic regime. These actively functionalized nanoparticles have been delivered to the targeted cells with higher selectivity, minimal toxicity and better retention in the cell. Numerous approaches and strategies have been designed till date for successful delivery of drug to cancer cells. The techniques have shown tremendous improvement in getting normalcy of carcinomas but a few have been marketed so far. Indeed, receptor based drug targeting approach through molecular signal transduction pathways involved in skin cancer development will provide insight into squamous carcinoma. Despite of these, other such challenges in drug delivery to squamous cell carcinoma need further clarification.

Survivorship of patients with head and neck cancer receiving care in a tertiary health facility in Nigeria.

BackgroundHead and neck cancer (HNC) is a major clinical and public health concern worldwide which impairs the vital functions of life. The treatment of metastatic HNCs is mainly palliative. This study examined the survival patterns and treatment outcomes in patients with HNCs in a tertiary hospital in Nigeria.Materials and methodsA review of the case files and treatment cards of patients with histological diagnosis of HNCs seen between January 2002 and December 2011 at the Radiotherapy Department, University College Hospital, Ibadan, was conducted. A total of 494 cases were identified, of which 481 had valid records. Analyses were done using Kaplan–Meier survival function and Cox proportional hazard regression techniques at 5% significance level.ResultsThe median age of patients was 42 years with a male-to-female ratio of 2:1. Most patients presented at stages 3 (50.7%) and 4 (36.8%). Nasopharyngeal carcinoma was the most common (42.6%) HNC, followed by paranasal sinus (17.7%) and laryngeal cancer (11.6%). The lung was the most common site of metastasis (25.5%). Patients who presented at stages 1 and 4 disease had a median survival of 7.8 years and 1.9 years, respectively. Patients treated with a combination of chemotherapy and radiotherapy had a median survival of 8.0 years compared with those who had a single modality of treatment (~6.3 years).ConclusionPatient survival was inversely proportional to the stage of the disease. To encourage the early presentation of HNC cases, health education of the population on routine medical check-ups and on the symptoms suggestive of HNC is recommended. Health care providers should be trained to refer suspected cases promptly to tertiary health facilities for management.

Modern Management of Nasal Hemangiomas

Current treatment approaches for infantile hemangiomas of the nose include observation, pharmacologic agents, surgery, and/or laser therapy. Because of the known functional, social, and cosmetic effect of nasal deformities, obtaining the best possible result is critical. Optimal timing, type, duration, and extent of therapy remain unclear. Results of a review of 86 patients (64 females and 22 males; mean age, 4.8 months [range, 2 days-23 years]) with infantile hemangiomas of the nose treated from January 1, 1999, to December 31, 2015, and a review of the literature are presented to gain insight into the preferred approach to the treatment of these lesions. Patients underwent single-modality and multimodality treatment with pulsed-dye laser (n = 73), oral corticosteroids (n = 11), intralesional corticosteroids (n = 2), propranolol hydrochloride (n = 30), and surgery (n = 50). The treatment decision algorithms and outcomes based on tumor phase and infantile hemangioma subtype are reviewed in detail. Nine articles met the criteria to be included in the literature review. Literature from the era before the approval of propranolol advocates for early use of oral or intralesional corticosteroids followed by surgery or pulsed-dye laser in cases of unacceptable outcomes. Literature from the era after the approval of propranolol supports early initiation of oral β-blockers until proliferation ceases or until additional intervention is necessary. Despite a lack of higher levels of evidence, there exists a general consensus between the literature and clinical experience advocating for early multimodality treatment to achieve the best result possible by the time the children reach certain sociodevelopmental milestones.

Abstract 5843: Role of CDK9 inhibition as a sensitizer to radiation in esophageal adenocarcinoma: In vitro and in vivo efficacy study

Abstract Preoperative chemoradiation in neoadjuvant setting is the standard of care for loco-regional esophageal adenocarcinoma (EAC). However, less than 30% of patients develop complete pathological response indicating need for newer therapeutic strategies. Cyclin dependent kinase 9 (CDK9) is found to be over expressed in EAC compared to Barrett’s esophagus. Our previous studies demonstrated strong antitumor effects on inhibition of CDK9 in EAC both in vitro and in vivo. Here we report augmented tumor regression in irradiated xenografts on combination with Flavopiridol, a well-established clinically used CDK inhibitor, compared to single modality treatments. In vitro studies indicate that Flavopiridol could radiosensitize FLO-1 and SKGT4 EAC cells with sustained 53BP1 foci especially in SKGT4 cells. Flavopiridol and BAY1143572, a more selective inhibitor of CDK9, could radiosensitize additional EAC radiation sensitive and resistant cell lines (SKGT4-R, OE-33 and OE-33-R) as analyzed by MTT assay, apoptosis, formation of 53BP1 foci and clonogenic assay. Flavopiridol and BAY1143572 showed a radio-synergistic action by downregulating MCL-1 and Axl. In conclusion, the radio-sensitizing capacities of CDK9 inhibitors presented here suggest that their adjuvant administration might improve EAC therapy. Note: This abstract was not presented at the meeting. Citation Format: Omkara Lakshmi M. Veeranki, Rashmi Dokey, Alicia Mejia, Zhimin Tong, Jianhu Zhang, Yawei Qiao, Pankaj Kumar Singh, Riham Katkhuda, Barbara Minoo, Jaime Rodriguez Canales, Steven Lin, Sunil Krishnan, Dipen Maru. Role of CDK9 inhibition as a sensitizer to radiation in esophageal adenocarcinoma: In vitro and in vivo efficacy study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5843. doi:10.1158/1538-7445.AM2017-5843

Diffuse Infiltrating Oligodendroglioma and Astrocytoma.

The new 2016 WHO brain tumor classification defines different diffuse gliomas primarily according to the presence or absence of IDH mutations ( IDH-mt) and combined 1p/19q loss. Today, the diagnosis of anaplastic oligodendroglioma requires the presence of both IDH-mt and 1p/19q co-deletion, whereas anaplastic astrocytoma is divided into IDH wild-type ( IDH-wt) and IDH-mt tumors. IDH-mt tumors have a more favorable prognosis, and tumors with low-grade histology especially tend evolve slowly. IDH-wt tumors are not a homogeneous entity and warrant further molecular testing because some have glioblastoma-like molecular features with poor clinical outcome. Treatment consists of a resection that should be as extensive as safely possible, radiotherapy, and chemotherapy. Trials of patients with newly diagnosed grade II or III glioma have shown survival benefit from adding chemotherapy to radiotherapy compared with initial treatment using radiotherapy alone. Both temozolomide and the combination of procarbazine, lomustine, and vincristine provide survival benefit. In contrast, trials that compare single modality treatment of chemotherapy alone with radiotherapy alone did not observe survival differences. Currently, for patients with grade II or III gliomas who require postsurgical treatment, the preferred treatment consists of a combination of radiotherapy and chemotherapy. Low-grade gliomas with favorable characteristics are slow-growing tumors. When deciding on the timing of postsurgical treatment with radiotherapy and chemotherapy, both clinical and molecular factors should be taken into account, but a more conservative approach can be considered initially in some of these patients. The factor that best predicts benefit of chemotherapy in grade II and III glioma remains to be established.

Multicenter Evaluation of Biochemical Relapse–Free Survival Outcomes for Intraoperatively Planned Prostate Brachytherapy Using an Automated Delivery System

To report biochemical recurrence in prostate cancer treated with intraoperatively planned low-dose-rate prostate brachytherapy using an automated delivery system (IO-LDRB). Between 2003 and 2013, 2608 patients from 3 centers were treated with IO-LDRB as single-modality treatment for low or low-tier intermediate-risk prostate cancer. Databases from the 3 centers have been analyzed. These independent databases were collected prospectively. Patient, tumor, and treatment characteristics were then compared, Kaplan-Meier survival estimates of biochemical relapse-free survival (bRFS) were generated, and the Cox proportional hazards model was used to determine factors predicting for relapse. A total of 2608 patients with a median follow-up of 4.7 (interquartile range, 3.1-6.9) years were analyzed. Median age was 64 (range, 42-84) years. In these patients, median initial prostate-specific antigen was 5.5ng/mL, 74% were T1, and 26% were T2; 73% were Gleason 6, and 25% Gleason 7. Median percentage of biopsy cores positive was 33%, and median gland volume was 34.2 cm3. Eleven percent of patients received hormones for a median of 3.0months before implantation. Median seed activity was 0.437mCi, D90 (dose covering 90% of the prostate volume) was 186.7Gy, and V100 was 99.37%. Biochemical relapse was observed in 124 patients (4.8%), and median time to failure was 4.0years. Predicted bRFS was 93% at 7years. On Cox regression bRFS was dependent only on D90 at the time of implantation and prostate-specific antigen density. This study demonstrates that IO-LDRB is an effective treatment option for patients with low and low-tier intermediate-risk prostate cancer. Rates of biochemical relapse remain low several years after treatment. These results compared favorably to published manual preplan technique results.

Tumor-targeted IL-12 combined with local irradiation leads to systemic tumor control via abscopal effects in vivo

ABSTRACT NHS-IL12 is an immunocytokine, a fusion protein of IL12's functional domains and a necrosis-targeting antibody, which has shown significant effects against human rhabdomyosarcoma xenografts in a humanized tumor model, including terminal growth arrest and differentiation of the tumor cells. Here, we locally irradiated the tumors, increasing necrosis and consequently intratumoral immune cytokine availability, and asked whether this effect may surmount efficacy of single treatment modality. Humanized mice bearing bilateral rhabdomyosarcoma xenografts were evaluated for tumor burden and survival after irradiation, systemic NHS-IL12 therapy or a combination of both. Intratumoral immune compartments were characterized by immunohistochemistry and molecular methods. TH1-cytokine dependency of underlying effector mechanisms were investigated in vitro in several human tumor cell lines. NHS-IL12 when combined with irradiation terminally arrested tumor growth and significantly improved survival. Combination treatment induced dense intratumoral T-cell infiltrates, clonal epitope-specific T-cell expansions, expression of cytotoxins, decreased pro-tumorigenic cytokines and induced senescence and differentiation in the cancer cells. Senescence and differentiation were reproduced in vitro and confirmed to be dependent on TH1 cytokines IFNγ and TNF-α. NHS-IL12 and irradiation together induced broad intratumoral TH1 biased NK and T-cell compartments, established antitumoral cytokine profiles and irreversibly growth arrested tumor cells, leading to systemic cancer control and improved survival. For the first time, we describe immune-induced senescence as a novel mechanism resulting from a treatment regimen combining irradiation with immunotherapy.

Endoscopic video-assisted transoral resection of lateral oropharyngeal tumors.

Endoscopic, video-assisted transoral resection of oropharyngeal tumors is a novel technique carried out using common instruments present in most otolaryngology departments. The technique facilitates oropharyngeal resection akin to transoral robotic surgery (TORS) without the need for a robot. A dual surgeon approach, analogous to that of endoscopic skull base surgery is used. Each surgeon can actively participate in the resection with several key advantages over current techniques. The technique is applicable to departments internationally especially where the use of a robot is prohibited by cost or availability. This is especially important given the resection of oropharyngeal tumours offers the opportunity of single modality treatment or reduced intensity adjuvant treatment compared to traditional non-surgical therapy.

Oncological outcome following de-intensification of treatment for stage I and II HPV negative oropharyngeal cancers with transoral robotic surgery (TORS): A prospective trial

ObjectiveThis prospective study aimed to see long-term oncological outcome of Transoral Robotic Surgery as single modality treatment for cT1-T2 N0 HPV negative oropharyngeal malignancies. MethodFrom March 2013 to October 2015, 57 patients with early stage oropharyngeal carcinoma underwent Transoral robotic surgery (TORS) with neck dissection using daVinci® Surgical system. Patients were evaluated for disease free survival, overall survival, locoregional and distant metastasis. Results57 patients (48 males and 9 females) underwent TORS for early stage oropharyngeal carcinoma. All patients underwent ipsilateral neck dissection and 12 patients underwent bilateral neck dissection. 49 patients with final histopathology suggestive of stage I and II disease did not received any adjuvant treatment. Mean age at presentation was 59.4years (37–88years). Most common site of involvement was the base of tongue (BOT) in 31 (54.8%) patients. Twenty-four (42.1%) patients were cT1 and 33 (57.9%) were cT2 at presentation. During follow-up, 2 (4.2%) patients recurred locoreginally and 1 (2.1%) patient had distant metastasis. Two patients expired due to causes other than malignancy. Forty-three (89.6%) patients were disease free on an average follow-up of 29months with an overall survival of 93.8% at mean follow-up of 29months. ConclusionTransoral Robotic Surgery as a single modality treatment is a good option for cure in HPV negative early resectable oropharyngeal malignancies which are relatively unresponsive to radiation. TORS can be used to de-intensify the treatment of early stage oropharyngeal carcinoma and thus avoid the early and late toxicities associated with Radiotherapy/Chemoradiotherapy.

Targeted superparamagnetic nanoparticles coated with 2-deoxy-d-gloucose and doxorubicin more sensitize breast cancer cells to ionizing radiation

IntroductionNanoparticles are promising as a new approach to enhance chemo- radiotherapy efficiency in breast cancer mainly via targeted therapy. Materials & methodsSKBR3 and T47D breast cancer cells were treated with superparamagnetic mesoporous hydroxyapatite nanocomposites (SPmHANs)conjugated with 1 μM doxorubicin and 0.5 mM 2-Deoxy-d-Glucose and irradiated with 1 and 2 Gy gamma rays in vitro. The treatment toxicity and also the apoptosis/necrosis ratio were measured by MTT assay and also ELISA cell death detection PLUS, respectively. ResultsThe decreased cell viability with the combined treatment, with determined 42% loading efficiency for 200 ppm 2DG and 93% for5ppm doxorubicin on SPmHANs in PH about 7.4 and 5.5, were calculated to 60.9% and 68% compared to radiotherapy alone inT47D and SKBR3 cells (both with p < 0.05), respectively. ConclusionBreast cancer cure may boost from The combined targeted nanoparticle treatment with doxorubicin and 2-Deoxy-d-Glucose may boost breast cancer radiotherapy by improved chemodrug localization, increased cytotoxicity in tumor cells and decreased single modality treatment doses.

Radiation therapy for localized malignant pleural mesothelioma: a propensity score-matched analysis of the National Cancer Data Base

The objectives of this study were to analyze rates of radiation therapy (RT) utilization for malignant pleural mesothelioma (MPM) and evaluate the association between RT and overall survival (OS). The National Cancer Data Base (NCDB) was queried to identify patients with non-metastatic MPM diagnosed between 2004 and 2013. RT was defined as receipt of 40-65Gy of external beam radiation therapy to the chest wall, lungs, or pleura. Multivariable logistic regression was performed to identify predictors of RT receipt. OS was estimated using the Kaplan-Meier method. Propensity score matching was performed to verify the effect of RT on OS. Among 14,090 MPM patients, 3.6% received RT. Younger age, lower co-morbidity score, private insurance, surgical resection, and receipt of chemotherapy were associated with increased RT utilization. Patients who received RT had higher crude 2 and 5-year OS rates (33.9 and 12.6%, respectively) compared to patients who did not (19.5 and 5.3%, respectively; p < 0.001). In multivariable analysis and propensity matched analysis, definitive RT was significantly associated with improved survival (adjusted hazard ratio [adj HR] 0.78, 95% CI 0.70–0.87) and (adj HR 0.77, 95% CI 0.67–0.89), respectively. Compared to no therapy, surgery and RT (adj HR 0.41, 95% CI 0.31–0.54) and trimodality therapy (adj HR 0.47, 95% CI 0.40–0.55) were associated with the best survival. The rate of RT utilization for non-metastatic MPM has remained low over the past decade. Patients who received RT had improved OS. Combined modality therapy was associated with a greater improvement in survival than single modality treatment.

Overcoming resistance to immune checkpoint blockade with RNA-loaded nanoparticles.

117 Background: While checkpoint blockade has shown promising survival benefits in patients with solid tumors, immune escape through loss of MHCI expression juxtaposed to an immunoregulatory milieu remain significant hurdles. To overcome these limitations, we developed a novel treatment platform, which leverages the use of commercially available and clinically translatable nanoparticles (NPs) that can be combined with tumor-derived RNA to activate systemic immunity and re-program the intratumoral microenvironment from a regulatory into an immune activated locale. Methods: Since local vaccination strategies are mired with poor immunogenicity, we assessed if i.v. delivery of tumor-derived RNA encapsulated in lipophilic NPs could activate peripheral and intratumoral antigen presenting cells (APCs) for induction of therapeutic anti-tumor immunity in pre-clinical murine melanoma models. Results: We identified a clinically translatable NP formulation that when administered intravenously, mediates release of inflammatory cytokines (i.e. CCL2, IFN-alpha) into serum, systemically activates host APCs in reticuloendothelial organs, and induces precipitous upregulation of MHCI and immune activation markers (i.e. CD86) within the tumor microenvironment. Both model-antigen encoding RNA and physiologically-relevant tumor-derived RNA, when encapsulated in NPs, could expand potent anti-tumor T-cell immunity. We demonstrated that RNA-NPs harness the anti-viral defense mechanism against tumor antigens in a type I interferon dependent manner, and can be further engineered to deliver combinatorial therapies by co-encapsulating mRNAs encoding for immunomodulatory molecules (i.e. HCV PAMPs, GM-CSF). In a pre-clinical melanoma model, RNA-NPs mediate anti-tumor efficacy and significantly enhance activity of immune checkpoint mAbs when used in combination. Conclusions: By employing a systemic RNA-NP formulation encoding for both tumor RNAs and immunomodulatory molecules, as an innovative and versatile platform for delivering combinatorial therapeutics via a single treatment modality, this platform can be harnessed to simultaneously target tumor antigens and re-program the intratumoral microenvironment

Role of Antibiotic Cement Coated Nailing in Infected Nonunion of Tibia.

IntroductionInfected nonunion of long bones is a chronic and debilitating disorder. It is more difficult to deal with when the implant used for internal fixation itself becomes a potential media for infection because of bacterial adhesion and biofilm formation. Traditionally, it is managed by two-stage procedure for controlling the infection first and then treating the nonunion. This study has been undertaken to explore antibiotic cement coated nailing as single stage treatment modality for treating infection and achieving stability at the same time.Materials and MethodsTwenty patients (above 18 years of age) with infected nonunion of tibia with bone gap less than 2 cm were managed using antibiotic cement coated K-nail. Antibiotic cement nail was prepared using endotracheal tube method. Antibiotics used were a combination of vancomycin and teicoplanin.ResultsInfection was controlled in 95% of the patients. Bony union was achieved in 12 of 20 (60%) patients with antibiotic cement nailing as the only procedure with average time of union of 32 weeks. Remaining 8 patients required additional procedures like bone grafting or exchange nailing and these were done in six patients, with union of fracture. Two patients refused to undergo further procedures. Complications encountered were difficult nail removal in three cases, broken nail in two cases, and bent nail in one case. Recurrence of infection was observed in two patients. Average period of follow-up was 13 months.ConclusionAntibiotic cement impregnated nailing is a simple, economical and effective single stage procedure for the management of infected nonunion of tibia. It is advantageous over external fixators, as it eliminates the complications of external fixators and has good patient compliance. The method utilizes existing easily available instrumentation and materials and is technically less demanding, and therefore can be performed at any general orthopaedic center.

Cost Analysis of Oral Cancer Treatment in a Tertiary Care Referral Center in India

Introduction: As much as the number of oral cancer patients is a heavy burden to the health care system in India, so much is the economic burden to the patient and the relatives, especially in India where most do not have any financial cover for their medical expenditure. Objectives: To find out the approximate cost of treatment of oral cancer through various modalities, and calculate the proportion of direct and indirect expenses, and then identify the factors which would increase the indirect expenses so as to come up with recommendations which will reduce the indirect cost thereby reducing the financial burden to the patient.Methods: A retrospective observational study was done in a tertiary care center for cancer treatment and the direct cost (medical expense), indirect cost (non-medical expense) incurred by the patients, their economic status and source of fund for payment of the expenses were obtained. Results: The proportion of indirect cost was about 38.72% of the total cost for patients who underwent a single modality treatment with surgery, around 34.73% for a combination treatment with surgery and RT (Radiotherapy), about 79.63% for treatment with conventional Radiotherapy without surgery and about 49.61% for treatment with IMRT (Intensity Modulated Radio Therapy) without surgery. Availability of financial aid or cover is abysmally poor. The rate of discontinuance of treatment is also very high according to this study.Conclusion: The proportion of the indirect cost is very high and the total expenditure can be reduced by approximately 30% by following measures discussed in this article.

ED15.02 Chemotherapy and Targeted Therapies of Thymic Malignancies

ED15.02 Chemotherapy and Targeted Therapies of Thymic Malignancies

Transoral surgery in early-stage laryngeal cancer

Single modality treatment is advocated for early laryngeal cancer, providing superior functional outcome and crucially options for further treatment in the event of local tumor recurrence. Options include surgery (mainly in the form of endolaryngeal techniques) or radiotherapy. With no prospective direct randomized controlled trials available, the choice of treatment following multidisciplinary discussion rests on a combination of tumor, patient and local expertise factors, with ultimately patient choice taking precedence. However, recently published data support the case for primary surgery on the basis of both organ preservation and health economics in early laryngeal cancer. We present an evidence-based review of the current literature in the management of primary and recurrent early laryngeal cancer.

Biodegradable Core-shell Dual-Metal-Organic-Frameworks Nanotheranostic Agent for Multiple Imaging Guided Combination Cancer Therapy.

Metal-organic-frameworks (MOFs) possess high porosity, large surface area, and tunable functionality are promising candidates for synchronous diagnosis and therapy in cancer treatment. Although large number of MOFs has been discovered, conventional MOF-based nanoplatforms are mainly limited to the sole MOF source with sole functionality. In this study, surfactant modified Prussian blue (PB) core coated by compact ZIF-8 shell (core-shell dual-MOFs, CSD-MOFs) has been reported through a versatile stepwise approach. With Prussian blue as core, CSD-MOFs are able to serve as both magnetic resonance imaging (MRI) and fluorescence optical imaging (FOI) agents. We show that CSD-MOFs crystals loading the anticancer drug doxorubicin (DOX) are efficient pH and near-infrared (NIR) dual-stimuli responsive drug delivery vehicles. After the degradation of ZIF-8, simultaneous NIR irradiation to the inner PB MOFs continuously generate heat that kill cancer cells. Their efficacy on HeLa cancer cell lines is higher compared with the respective single treatment modality, achieving synergistic chemo-thermal therapy efficacy. In vivo results indicate that the anti-tumor efficacy of CSD-MOFs@DOX+NIR was 7.16 and 5.07 times enhanced compared to single chemo-therapy and single thermal-therapy respectively. Our strategy opens new possibilities to construct multifunctional theranostic systems through integration of two different MOFs.

P3.03-031 Definitive Radiation Therapy is Associated with Improved Survival in Non-Metastatic Malignant Pleural Mesothelioma: Topic: Mesothelioma Clinical

To analyze rates of definitive radiation therapy (RT) utilization for malignant pleural mesothelioma (MPM) and evaluate the association between RT and overall survival (OS). The National Cancer Data Base (NCDB) was queried to identify patients with non-metastatic MPM diagnosed between 2004 and 2013. Definitive RT was defined as receipt of 40-65 Gy of external beam radiation therapy to the chest wall, lungs, or pleura. Multivariate logistic regression was performed to identify predictors of RT receipt. OS was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to identify predictors of mortality. Propensity score matching was performed to verify the effect of definitive RT on OS. Among 14,090 MPM patients, 3.6% received RT. Younger age, lower co-morbidity score, private insurance, surgical resection, and receipt of chemotherapy were associated with increased RT utilization. Patients who received RT had higher crude 2 and 5-year OS rates (33.9% and 12.6%, respectively) compared to patients who did not (19.5% and 5.3%, respectively; p<0.001). On multivariable analysis and propensity matched analysis, definitive RT was associated with improved survival (adjusted hazard ratio [adj HR] 0.78, 95% CI 0.70-0.87) and (adj HR 0.77, 95% CI 0.67-0.89), respectively. Compared to no therapy, surgery and RT (adj HR 0.41, 95% CI 0.31-0.54) and trimodality therapy (adj HR 0.47, 95% CI 0.40-0.55) were associated with the best survival.Tabled 1Comparison of Overall Survival According to Definitive RT2-yr rate95% CI5-yr rate95% CIpAdjusted HR95% CINo RT19.5%18.8-20.35.3%4.9-5.8<0.0011.00RefRT33.9%29.4-38.412.6%9.4-16.3<0.0010.780.70-0.87 Open table in a new tab The rate of definitive RT utilization for non-metastatic MPM has remained low over the past decade. Patients who received RT had improved OS, suggesting a role for increased utilization, particularly with the advancement in RT techniques. Combined modality therapy was associated with a greater improvement in survival than any single modality treatment.

Rationale of Surgery in Locally Advanced and Oligometastatic Prostate Cancer

There is no clear consensus for the best treatment of men with locally advanced prostate cancer. As a first step, radiation therapy or primary hormone therapy or radical prostatectomy with extended pelvic lymph node dissection is used. But it seems impossible to have a good oncologic result with single treatment modality. Traditionally, external beam radiation therapy with adjuvant hormone therapy is most preferred treatment method in locally advanced prostate cancer and radical prostatectomy has not been routinely used because of high rates of margin positive and lymph node metastasis. But, recently published articles showed that surgery in multimodal setting is effective treatment modality and not inferior to radiation therapy in oncologic outcomes. Perioperative morbidities of surgery and incontinence rates are similar to surgery of organ confined diseases, and patients with primary radiotherapy seem to have high rate of lower urinary tract symptoms and radiation related complications compared with radical prostatectomy with adjuvant radiotherapy. There is still controversy in regard to performing surgery for locally advanced prostate cancer. We review the studies with surgery in locally advanced prostate cancer and compare with radiation therapy in multimodal setting, and review the studies with surgery in oligometastatic prostate cancer. Key Words: Radical prostatectomy; Locally advanced prostate cancer; Oligometastatic prostate cancer.