Primary lung tumour stereotactic body radiotherapy followed by concurrent mediastinal chemoradiotherapy and adjuvant immunotherapy for locally advanced non-small-cell lung cancer: a multicentre, single-arm, phase 2 trial.

Background: Patients with locally advanced non-small-cell lung cancer (NSCLC) who undergo concurrent chemotherapy and radiotherapy often experience synergistic toxicity, and local regional control rates remain poor. We assessed the activity and safety outcomes of primary tumour stereotactic body radiotherapy (SBRT) followed by conventional chemoradiotherapy to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced NSCLC.

Methods: In this multicentre, single-arm, phase 2 trial, patients aged 18 years and older were enrolled at eight regional cancer centres in North Carolina and South Carolina, USA.

The Association Between Radiation Therapy Dose and Overall Survival in Patients With Intracranial Infiltrative Low-Grade Glioma Treated With Concurrent and/or Adjuvant Chemotherapy.

Purpose: Previous trials have shown no benefit for radiation therapy (RT) dose escalation when RT is given as adjuvant monotherapy for infiltrative low-grade glioma (LGG). However, the current standard of care for high-risk LGG is RT with concurrent and/or adjuvant chemotherapy. The effect of RT dose escalation on overall survival (OS) in the setting of concurrent and/or adjuvant chemotherapy is not well established.

The effect of adjuvant radiotherapy on overall survival in adults with intracranial ependymoma.

Background: Adult intracranial ependymoma is rare, and the role for adjuvant radiotherapy (RT) is not well defined.

Methods: We used the National Cancer Database (NCDB) to select adults (age ≥ 22 years) with grade 2 to 3 intracranial ependymoma status postresection between 2004 and 2015 and treated with adjuvant RT vs observation. Four cohorts were generated: (1) all patients, (2) grade 2 only, (3) grade 2 status post-subtotal resection only, (4) and grade 3 only.

Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair.

The hereditary cancer syndromes hereditary leiomyomatosis and renal cell cancer (HLRCC) and succinate dehydrogenase-related hereditary paraganglioma and pheochromocytoma (SDH PGL/PCC) are linked to germline loss-of-function mutations in genes encoding the Krebs cycle enzymes fumarate hydratase and succinate dehydrogenase, thus leading to elevated levels of fumarate and succinate, respectively. Here, we report that fumarate and succinate both suppress the homologous recombination (HR) DNA-repair pathway required for the resolution of DNA double-strand breaks (DSBs) and for the maintenance of genomic integrity, thus rendering tumor cells vulnerable to synthetic-lethal targeting with poly(ADP)-ribose polymerase (PARP) inhibitors. These results identify HLRCC and SDH PGL/PCC as familial DNA-repair deficiency syndromes, providing a mechanistic basis to explain their cancer predisposition and suggesting a potentially therapeutic approach for advanced HLRCC and SDH PGL/PCC, both of which are incurable when metastatic.

Post-operative radiotherapy is associated with improved survival in esophageal cancer with positive surgical margins.

Background: The optimal treatment for early-stage esophageal cancer with positive surgical margins after an upfront esophagectomy is not well-defined. This study investigates the effect of post-operative radiotherapy (PORT) on overall survival (OS) in clinical stage I-II patients with positive margins.

Methods: We identified patients diagnosed between 2004 and 2012 with clinical stage I-II esophageal carcinoma from the National Cancer Data Base (NCDB) who underwent an upfront esophagectomy.

Patterns of care and outcomes for use of concurrent chemoradiotherapy over radiotherapy alone for anaplastic gliomas.

Background And Purpose: The role of concurrent chemoradiotherapy (CRT) for anaplastic gliomas is undefined and patterns of care are under-reported. To address the knowledge gap, we examined use of CRT for grade III gliomas compared to radiotherapy (RT) alone.

Material And Methods: In an observational study design cohort from the National Cancer Database, we identified 4437 adult patients receiving surgery followed by either CRT or RT for supratentorial anaplastic glioma in 2003-2011.

Local DNA Repair Inhibition for Sustained Radiosensitization of High-Grade Gliomas.

High-grade gliomas, such as glioblastoma (GBM) and diffuse intrinsic pontine glioma (DIPG), are characterized by an aggressive phenotype with nearly universal local disease progression despite multimodal treatment, which typically includes chemotherapy, radiotherapy, and possibly surgery. Radiosensitizers that have improved the effects of radiotherapy for extracranial tumors have been ineffective for the treatment of GBM and DIPG, in part due to poor blood-brain barrier penetration and rapid intracranial clearance of small molecules. Here, we demonstrate that nanoparticles can provide sustained drug release and minimal toxicity.

Role of Adjuvant Treatment in Esophageal Cancer With Incidental Pathologic Node Positivity.

Background: The optimal adjuvant treatment for cT1-2 N0 esophageal cancer patients found to have pathologic nodal involvement after an upfront operation is unclear. This study investigated the effects of postoperative chemotherapy and chemoradiation therapy on overall survival in cT1-2 N0 patients with incidental pN disease stratified by margin status.

Methods: We identified cT1-2 N0 M0 esophageal carcinoma patients from 2004 to 2012 from the National Cancer Data Base.

The role of radiation in treating glioblastoma: here to stay.

Despite numerous efforts over the past several decades, few therapeutic breakthroughs in the treatment of GBM have been realized, and even these have yielded only incrementally modest gains. Radiotherapy remains a crucial component in the management of this disease. In this review, the historical basis for inclusion of radiotherapy as part of the therapeutic regimen for GBM is examined.

Trends in stereotactic body radiation therapy for stage I small cell lung cancer.

Objectives: We aimed to report trends in stereotactic body radiation therapy (SBRT) utilization, dose prescriptions, and chemotherapy administration for stage I small cell lung cancer (SCLC) in the United States.

Materials And Methods: The National Cancer Data Base (NCDB) was used to identify patients with cT1-2 N0 SCLC treated with SBRT between 2004 and 2013. Trends in SBRT use and dose prescription were analyzed over time.

Role of Adjuvant Therapy for Node-Negative Lung Cancer Invading the Chest Wall.

Introduction: The present study investigated the effect of adjuvant chemotherapy and radiation on survival among patients undergoing chest wall resection for T3N0 non-small cell lung cancer (NSCLC).

Materials And Methods: Patients with T3N0 NSCLC who underwent chest wall resection were identified in the National Cancer Data Base in 2004 to 2012. The cohort was divided into patients who had received adjuvant chemotherapy, radiation therapy, chemoradiation therapy, or no adjuvant treatment.

A Comparison of Prognostic Ability of Staging Systems for Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

Importance: The current American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system, developed for human papillomavirus (HPV)-unrelated disease, discriminates poorly when applied to HPV-related oropharyngeal squamous cell cancer (OPSCC), leading to calls for a new staging system.

Objective: To compare the prognostic ability of the AJCC/UICC seventh edition staging system; a recently proposed system, the International Collaboration on Oropharyngeal Cancer Network for Staging (ICON-S); and a novel objectively derived system for HPV-related OPSCC using a national database of patients primarily treated with either radiation or surgery.

Design, Setting, And Participants: In this observational study, patients with HPV-related nonmetastatic OPSCC were identified in the National Cancer Database between 2010 and 2012.

Timing of Surgery after Neoadjuvant Chemoradiation in Locally Advanced Non-Small Cell Lung Cancer.

Introduction: A subset of patients with potentially resectable clinical stage IIIA NSCLC are managed with trimodality therapy. However, little data exist to guide the timing of surgery after neoadjuvant therapy. This study examined whether the time interval between neoadjuvant chemoradiation (NCRT) and surgical resection affects overall survival.

Success and Failures of Combined Modalities in Glioblastoma Multiforme: Old Problems and New Directions.

Glioblastoma multiforme (GBM) is an aggressive intracranial tumor characterized by local and distant brain relapse despite aggressive therapy. Current standard treatment includes surgical resection followed by radiation with concurrent and adjuvant temozolomide as part of a combined modality approach. In this review, the historical basis for the current standard treatment is discussed as well as other recent combined modality successes and failures.

The Association Between Evaluation at Academic Centers and the Likelihood of Expectant Management in Low-risk Prostate Cancer.

Objective: To identify factors associated with expectant management (EM) in a large cohort of men with low-risk prostate cancer based on cancer center type (community vs academic). EM, consisting of active surveillance or observation for men with low-risk prostate cancer, is an increasingly recognized management option, given the morbidity and lack of a survival benefit associated with definitive treatment. However, the influence of cancer center type on treatment selection is uncertain.

Concurrent chemoradiotherapy versus radiotherapy alone for "biopsy-only" glioblastoma multiforme.

Background: Combined temozolomide and radiotherapy (RT) is the standard postoperative therapy for glioblastoma multiforme (GBM). However, the clearest benefit of concurrent chemoradiotherapy (CRT) observed in clinical trials has been among patients who undergo surgical resection. Whether the improved survival with CRT extends to patients who undergo "biopsy only" is less certain.

Who benefits from chemoradiation in stage III-IVA endometrial cancer? An analysis of the National Cancer Data Base.

Objective: Adjuvant therapy for advanced endometrial cancer (AEC) is not standardized. We investigated whether regional radiotherapy with chemotherapy (CRT) compared to chemotherapy alone (CT) was associated with improved overall survival (OS) in an AEC cohort and among subgroups by stage and histologic grade.

Methods: Women who received CT or CRT after hysterectomy and bilateral salpingo-oophorectomy for FIGO stage III-IVA AEC diagnosed in 2004-2012 were identified in the National Cancer Data Base.

Association Between Radiation Dose and Outcomes With Postoperative Radiotherapy for N0-N1 Non-Small Cell Lung Cancer.

Purpose: To review trends in the use of postoperative radiotherapy (PORT) in the modern era for N0-N1 margin-negative non-small cell lung cancer (NSCLC) following surgical resection and evaluate the association between PORT dose and overall survival.

Materials And Methods: We performed a retrospective study of nonmetastatic stage II and III N0-N1 margin-negative NSCLC surgically treated patients within the National Cancer Data Base from 2003 to 2011. Cox proportional hazards regression was performed for multivariable analyses of overall survival and PORT dose.

Role of Chemoradiotherapy in Elderly Patients With Limited-Stage Small-Cell Lung Cancer.

Purpose: To investigate outcomes for elderly patients treated with chemotherapy (CT) alone versus chemoradiotherapy (CRT) in the modern era by using a large national database.

Patients And Methods: Elderly patients (age ≥ 70 years) with limited-stage small-cell lung cancer clinical stage I to III who received CT or CRT were identified in the National Cancer Data Base between 2003 and 2011. Hierarchical mixed-effects logistic regression with clustering by reporting facility was performed to identify factors associated with treatment selection.

Changing practice patterns of Gamma Knife versus linear accelerator-based stereotactic radiosurgery for brain metastases in the US.

Objective: Single-fraction stereotactic radiosurgery (SRS) is a crucial component in the management of limited brain metastases from non-small cell lung cancer (NSCLC). Intracranial SRS has traditionally been delivered using a frame-based Gamma Knife (GK) platform, but stereotactic modifications to the linear accelerator (LINAC) have made an alternative approach possible. In the absence of definitive prospective trials comparing the efficacy and toxicities of treatment between the 2 techniques, nonclinical factors (such as technology accessibility, costs, and efficiency) may play a larger role in determining which radiosurgery system a facility may choose to install.

Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base.

Background: The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness.

Methods: Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base.

Comparison of survival outcomes among standard radiotherapy regimens in limited-stage small cell lung cancer patients receiving concurrent chemoradiation.

Objectives: The optimal radiotherapy dose in concurrent chemoradiation (CRT) for limited-stage small cell lung cancer (SCLC) is controversial. We compared the effectiveness of several high-dose chemoradiation regimens using a large national dataset.

Materials And Methods: Patients with non-metastatic SCLC treated with concurrent CRT were identified in the National Cancer Database base.