A Phase II Trial of Stereotactic Ablative Radiation Therapy as a Boost for Locally Advanced Cervical Cancer.

Purpose: Our purpose was to assess the feasibility, safety, and efficacy of stereotactic ablative radiation therapy (SAbR) as an alternative for intracavitary/interstitial brachytherapy boost for locally advanced cervical cancer (LACC) after initial chemoradiation.

Methods And Materials: A single arm institutional phase II study of SAbR as a boost for LACC was conducted. Eligible patients had LACC FIGO 2009 stage IB2-IVB, performance status 0 to 3, and one of the following: medically unfit or refused intracavitary or tumor extent required interstitial brachytherapy for coverage.

Impact of Biochemical Failure After Salvage Radiation Therapy on Prostate Cancer-specific Mortality: Competition Between Age and Time to Biochemical Failure.

Background: Disease progression following salvage radiotherapy (SRT) for prostate cancer (PC) is common, and the time to biochemical recurrence (BCR) is heterogeneous.

Objective: To describe the temporal distribution and clinical impact of BCR following SRT and model outcomes using patient age and time to BCR from SRT.

Design, Setting, And Participants: A retrospective multi-institutional study included 547 consecutive men with lymph node-negative PC receiving SRT from 1985 to 2013.

Association between treatment delays and oncologic outcome in patients treated with surgery and radiotherapy for head and neck cancer.

Background: This study sought to determine the oncologic impact of delays to surgery, radiotherapy, and completion of therapy in patients with head and neck squamous cell carcinoma.

Methods: The impact of biopsy to surgery (BTS) time, surgery to start of radiation time (STSR), and radiation treatment time (RTT) on locoregional recurrence (LRR), distant metastases (DMs), and cancer-specific mortality (CSM) was examined. The cumulative incidences (CI) of LRR, DMs, and CSM were examined using Fine-Gray testing.

The current state of oligometastatic and oligoprogressive non-small cell lung cancer.

Oligometastatic disease is defined as an intermediate state between localized and widespread metastatic disease. Given that in the oligometastatic state gross tumors represent the full extent of disease, there may be a role for curative local therapy despite metastatic disease. As nearly 60% of patients with non-small cell lung cancer (NSCLC) present with metastatic disease and another 45% of patients with initially localized disease will ultimately develop distant metastases, NSCLC represents a prime disease for aggressive intervention.

Patterns of Failure in Patients With Double Hit or Double Expressor Lymphomas: Implications for Radiation Therapy.

Purpose: Lymphomas with MYC and either BLC2 or BCL6 rearrangements or MYC and BCL-2 protein overexpression, classified as double-hit (DHL) or double-expressor (DEL) lymphomas, respectively, are associated with poorer response to standard immunochemotherapy. Optimal therapy is not clear, and little information exists on the contribution of consolidative radiation therapy in these patients. This study describes the patterns of failure of DHL/DEL in relation to initial sites of disease and indications for radiation therapy in unselected diffuse large B-cell lymphoma (DLBCL).

Intermediate Endpoints After Postprostatectomy Radiotherapy: 5-Year Distant Metastasis to Predict Overall Survival.

Background: Intermediate clinical endpoints (ICEs) prognostic for overall survival (OS) are needed for men receiving postprostatectomy radiation therapy (PORT) to improve clinical trial design.

Objective: To identify a potential ICE for men receiving PORT.

Design, Setting, And Participants: We performed an institutional review board-approved multi-institutional retrospective study of 566 men consecutively treated with PORT at tertiary care centers from 1986 to 2013.

Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial.

Importance: Patterns-of-failure studies suggest that in metastatic non-small-cell lung cancer (NSCLC) sites of gross disease at presentation are the first to progress when treated with chemotherapy. This knowledge has led to increased adoption of local ablative radiation therapy in patients with stage IV NSCLC, though prospective randomized evidence is limited.

Objective: To determine if intervening with noninvasive stereotactic ablative radiotherapy (SAbR) prior to maintenance chemotherapy in patients with non-progressive limited metastatic NSCLC after induction therapy led to significant improvements in progression-free survival (PFS).

Natural history of 'second' biochemical failure after salvage radiation therapy for prostate cancer: a multi-institution study.

Objectives: To describe the natural history of prostate cancer in men who experience a second biochemical recurrence (BCR) after salvage radiotherapy (SRT) after prostatectomy.

Patients And Methods: After undergoing SRT at one of two institutions between 1986 and 2013, 286 patients experienced a second BCR, defined as two rises in prostate-specific antigen (PSA) of ≥0.2 ng/mL above nadir.

Anatomical patterns of recurrence following biochemical relapse after post-prostatectomy salvage radiation therapy: a multi-institutional study.

Objectives: To characterise the frequency and detailed anatomical sites of failure for patients receiving post-radical prostatectomy (RP) salvage radiation therapy (SRT).

Patients And Methods: A multi-institutional retrospective study was performed on 574 men who underwent SRT between 1986 and 2013. Anatomical recurrence patterns were classified as lymphotrophic (lymph nodes only), osteotrophic (bone only), or multifocal if both were present.

Endoluminal and Interstitial Brachytherapy for the Treatment of Gastrointestinal Malignancies: a Systematic Review.

Radiation therapy is an integral component in the multimodality management of many gastrointestinal (GI) cancers at all stages of clinical presentation. With recent advances in technology and radiation delivery, external beam radiation therapy (EBRT) can be delivered with reduced toxicity. However, despite these advances, EBRT doses are still limited by the presence of radiosensitive serial structures near clinical targets in the GI tract.

Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival.

Purpose: Early salvage radiotherapy following radical prostatectomy for prostate cancer is commonly advocated in place of adjuvant radiotherapy. We aimed to determine the optimal definition of early salvage radiotherapy.

Materials And Methods: We performed a multi-institutional retrospective study of 657 men who underwent salvage radiotherapy between 1986 and 2013.

Stereotactic body radiation therapy for low and intermediate risk prostate cancer-Results from a multi-institutional clinical trial.

Background: We report the outcome of a phase I/II clinical trial of stereotactic body radiation therapy (SBRT) for low (LR) and select intermediate risk (IR) prostate cancer (PCa) patients.

Patients And Methods: Eligible patients included men with prostate adenocarcinoma with Gleason score 6 with PSA ≤ 20 or Gleason 7 with PSA ≤ 15 and clinical stage ≤ T2b. For the phase I portion of the study patients in cohorts of 15 received 45, 47.

Remote location interstitial brachytherapy with patient stabilization and subsequent transport to an outpatient center for treatment is safe and effective for the treatment of gynecologic malignancies.

Purpose: Interstitial brachytherapy is an essential component of definitive treatment for locally advanced gynecological malignancies. Although many outpatient centers are capable of delivering the radiation component of brachytherapy, they are not associated with an operative center for implant placement, limiting the ability to deliver appropriate care. In this study, we report on our experience with noncolocated implant placement and radiation delivery, and the impact of patient stabilization improvements on patient safety.

Pretreatment biopsy analysis of DAB2IP identifies subpopulation of high-risk prostate cancer patients with worse survival following radiation therapy.

Decreased expression of tumor suppressor DAB2IP is linked to aggressive cancer and radiation resistance in several malignancies, but clinical survival data is largely unknown. We hypothesized that pretreatment DAB2IP reduction would predict worse prostate cancer-specific survival (PCSS). Immunohistochemistry of pretreatment biopsies was scored by an expert genitourinary pathologist.

NSCLC cells demonstrate differential mode of cell death in response to the combined treatment of radiation and a DNA-PKcs inhibitor.

The current standard of care for lung cancer consists of concurrent chemotherapy and radiation. Several studies have shown that the DNA-PKcs inhibitor NU7441 is a highly potent radiosensitizer, however, the mechanism of NU7441's anti-proliferation effect has not been fully elucidated. In this study, the combined effect of NU7441 and ionizing radiation (IR) in a panel of non-small cell lung cancer cell lines (A549, H460 and H1299) has been investigated.

Polymeric nanoparticles for targeted radiosensitization of prostate cancer cells.

One of the many issues of using radiosensitizers in a clinical setting is timing daily radiation treatments to coincide with peak drug concentration in target tissue. To overcome this deficit, we have synthesized a novel nanoparticle (NP) system consisting of poly (lactic-co-glycolic acid) (PLGA) NPs conjugated with prostate cancer cell penetrating peptide-R11 and encapsulated with a potent radio-sensitizer 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441) to allow prostate cancer-specific targeting and sustained delivery over 3 weeks. Preliminary characterization studies showed that the R11-conjugated NPs (R11-NU7441 NPs) had an average size of about 274 ± 80 nm and were stable for up to 5 days in deionized water and serum.

DOC-2/DAB2 interacting protein status in high-risk prostate cancer correlates with outcome for patients treated with radiation therapy.

Purpose: This pilot study investigates the role of DOC-2/DAB2 Interacting Protein (DAB2IP) and enhancer of zeste homolog 2 (EZH2) as prognostic biomarkers in high-risk prostate cancer patients receiving definitive radiation therapy.

Methods And Materials: Immunohistochemistry was performed and scored by an expert genitourinary pathologist. Clinical endpoints evaluated were freedom from biochemical failure (FFBF), castration resistance-free survival (CRFS), and distant metastasis-free survival (DMFS).

Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance.

DAB2IP regulates autophagy in prostate cancer in response to combined treatment of radiation and a DNA-PKcs inhibitor.

Radiation therapy (RT) is an effective strategy for the treatment of localized prostate cancer (PCa) as well as local invasion. However, some locally advanced cancers develop radiation resistance and recur after therapy; therefore, the development of radiation-sensitizing compounds is essential for treatment of these tumors. DOC-2/DAB2 interactive protein (DAB2IP), which is a novel member of the Ras-GTPase activating protein family and a regulator of phosphatidylinositol 3-kinase-Akt activity, is often downregulated in aggressive PCa.

Effect of PF-02341066 and radiation on non-small cell lung cancer cells.

Recently, a fusion protein of echinoderm microtubule associated protein like-4 (EML4) and anaplastic lymphoma kinase (ALK) has been found in non-small cell lung cancer (NSCLC) patients. In addition, endogenous expression of phosphorylated c-Met was found to be increased in many invasive NSCLC cases. PF-02341066 (crizotinib) is a novel dual c-Met and EML4-ALK inhibitor, and preclinical studies have shown that treatment with ALK inhibitors leads to drastic tumor regression in xenograft models.

AZD5438, an inhibitor of Cdk1, 2, and 9, enhances the radiosensitivity of non-small cell lung carcinoma cells.

Purpose: Radiation therapy (RT) is one of the primary modalities for treatment of non-small cell lung cancer (NSCLC). However, due to the intrinsic radiation resistance of these tumors, many patients experience RT failure, which leads to considerable tumor progression including regional lymph node and distant metastasis. This preclinical study evaluated the efficacy of a new-generation cyclin-dependent kinase (Cdk) inhibitor, AZD5438, as a radiosensitizer in several NSCLC models that are specifically resistant to conventional fractionated RT.