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Chemoradiation is the standard treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), and thanks to the recent combination with immunotherapy, median survival has unexpectedly improved. This study aims to evaluate early changes in cardiac function after chemoradiotherapy (CRT) in LA-NSCLC by multimodal use of advanced imaging techniques.This is a prospective, observational cohort study. At the beginning of combined treatment, screening tests including blood samples, electrocardiogram (ECG), echocardiographic examination (TTE), and cardiac magnetic resonance were performed in all patients with LA-NSCLC. ECG and cardiac marker assays were performed weekly during treatment. ECG and TTE were performed at month 1 (M1) and month 3 (M3) after the end of CRT.This preliminary analysis included thirty-four patients with a mean age of 69.5 years. The median follow-up was 27.8 months. 62% of patients were in stage IIIA. Radiation therapy was delivered with a median total dose of 60 Gy with conventional fractionation. All patients were treated with concurrent CRT, and 65% of cases were platinum-based therapy. Global longitudinal strain (GLS) and ejection fraction (EF) progressively decreased from baseline to M1 and M3. There was a strong correlation between GLS and EF reduction (at M1: p = 0.034; at M3: p = 0.018). Cardiac arrhythmias occurred in eight patients (23.5%) at a mean follow-up of 15.8 months after CRT.Reduction in GLS is an early sign occurring after the end of CRT for LA-NSCLC. Future studies are needed to identify variables that can increase the risk of cardiac events in this patient population to implement adequate damage prevention strategies.

Background/Aim: The high sensitivity cardiac troponin T (Hs-cTnT) is a myocardial damage biomarker that could have a predictive value in patients who undergo radiotherapy for left sided breast cancer. The aim of this study was to evaluate the early effect of left whole breast radiotherapy (WB-RT) on serum Hs-cTnT levels and its correlation with pre-existing factors. Patients and Methods: The study was conducted from December 2017 to May 2018. Forty-five patients with early stage left-sided breast cancer who received adjuvant breast hypofractionated RT without prior chemotherapy were included. Serum levels of Hs-cTnT were obtained before, weekly during RT, and within one week after the end of treatment. Considering the physiological variations of serum levels, an increase in Hs-cTnT (∆Hs-cTnT) of more than 30% from the baseline value was chosen as a threshold. The main cardiovascular risk factors were recorded. Dose volume histograms (DVHs) were used to provide a quantitative analysis for the whole heart, left ventricle, and left anterior descending artery (LAD). Results: Twelve of 45 patients (26.6%) showed a ∆Hs-cTnT ≥30%. The maximum Hs-cTnT level was recorded in the last week of treatment. ∆Hs-cTnT was strongly associated with heart V5 (p=0.05) and hypertension (p=0.05). Multivariate analysis confirmed the importance of the heart V5 and correlated with ∆Hs-cTnT. Conclusion: The increase in Hs-cTnT serum levels during adjuvant WB-RT suggested a correlation with the cardiac radiation dose in chemotherapy-naive breast cancer patients. A longer follow-up is needed to correlate Hs-cTnT values with cardiac events.

Immune checkpoint inhibitors (ICPi) targeting programmed cell death 1(PD-1)/programmed cell death ligand-1 (PD-L1) have revolutionized the treatment of patients with advanced non-small cell lung cancer (NSCLC). Despite impressive success, only a small proportion of patients benefit from PD1/PDL1 inhibitors. Radiotherapy (RT) can induce a systemic anti-tumor immune response on local and distant tumors. Some preclinical and clinical evidence showed a critical role of RT to overcome acquired resistance to immunotherapy. Currently, durvalumab consolidation represents the new standard treatment for unresectable stage III NSCLC patients whose tumors express PDL1 on ≥1% of tumor cells (TC), and whose disease has not progressed following platinum-based chemoradiotherapy (CRT). In this review, we focus on the synergic effect of RT with ICPi and the new role that different RT schedules can play in combination with immunotherapy for early-stage NSCLC.

Background: Adult-type soft tissue sarcomas (STSs) are rare tumors representing about 1% of all adult malignant tumors. Their extreme histological heterogeneity places them among the most challenging fields of diagnostic pathology. The variability of clinical and prognostic presentation between the various histotypes reflects the different management that should be followed on a case-by-case basis. These features make STSs the case in point of how important it is a centralized and multidisciplinary approach. Summary: Surgery represents the mainstay in the treatment of localized STSs. Recently, more and more studies are making efforts to understand what the contribution of chemotherapy and radiotherapy with neoadjuvant and adjuvant intent may be both in unselected and selected histological subgroups. In fact, despite the improvement in overall survival seen in the past few years thanks to the adoption of a more radical surgical approach, mortality remains relatively high and the 5-year overall survival is around 65%. Key Messages: In this review, we comment upon the treatment of localized STSs of the extremity, trunk wall, and retroperitoneum and how surgery, radiotherapy, and chemotherapy can be integrated with each other and individually tailored. Nomograms can assist clinicians in this complex therapeutic decision-making process, through the identification of patients at higher risk of death or disease relapse.

The role of postoperative radiation therapy (PORT) in stage III N2 nonsmall cell lung cancer patients remains controversial. PORT is still widely used among European thoracic radiation oncology experts with a clear decrease in its use for patients with completely resected pN+ NSCLC after the presentation of LungART trial results at ESMO 2020. The full publication of the LungART trial hopefully will shed additional light on the dilemma of the decision-making process for PORT in completely resected pN+ patients and identify the appropriate patients who might benefit from PORT.Background: The role of postoperative radiation therapy (PORT) in stage III N2 NSCLC is controversial. We analyzed decision-making for PORT among European radiation oncology experts in lung cancer. Methods: Twenty-two experts were asked before and after presentation of the results of the LungART trial to describe their decision criteria for PORT in the management of pN+ NSCLC patients. Treatment strategies were subsequently converted into decision trees and analyzed. Results: Following decision criteria were identified: extracapsular nodal extension, incomplete lymph node resection, multistation lymph nodes, high nodal tumor load, poor response to induction chemotherapy, ineligibility to receive adjuvant chemotherapy, performance status, resection margin, lung function and cardiopulmonary comorbidities. The LungART results had impact on decision-making and reduced the number of recommendations for PORT. The only clear indication for PORT was a R1/2 resection. Six experts out of ten who initially recommended PORT for all R0 resected pN2 patients no longer used PORT routinely for these patients, while four still recommended PORT for all patients with pN2. Fourteen experts used PORT only for patients with risk factors, compared to eleven before the presentation of the LungART trial. Four experts stated that PORT was never recommended in R0 resected pN2 patients regardless of risk factors. Conclusion: After presentation of the LungART trial results at ESMO 2020, 82% of our experts still used PORT for stage III pN2 NSCLC patients with risk factors. The recommendation for PORT decreased, especially for patients without risk factors. Cardiopulmonary comorbidities became more relevant in the decision-making for PORT. (C) 2021 Elsevier Inc. All rights reserved.

PURPOSE This meta-analysis aims to combine and analyze randomized clinical trials comparing computed tomography lung screening (CTLS) versus either no screening (NS) or chest x-ray (CXR) in subjects with cigarette smoking history, to provide a precise and reliable estimation of the benefits and harms associated with CTLS. MATERIALS AND METHODS Data from all published randomized trials comparing CTLS versus either NS or CXR in a highly tobacco-exposed population were collected, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Subgroup analyses by comparator (NS or CXR) were performed. Pooled risk ratio (RR) and relative 95% CIs were calculated for dichotomous outcomes. The certainty of the evidence was assessed using the GRADE approach. RESULTS Nine eligible trials (88,497 patients) were included. Pooled analysis showed that CTLS is associated with: a significant reduction of lung cancer–related mortality (overall RR, 0.87; 95% CI, 0.78 to 0.98; NS RR, 0.80; 95% CI, 0.69 to 0.92); a significant increase of early-stage tumors diagnosis (overall RR, 2.84; 95% CI 1.76 to 4.58; NS RR, 3.33; 95% CI, 2.27 to 4.89; CXR RR, 1.52; 95% CI, 1.04 to 2.23); a significant decrease of late-stage tumors diagnosis (overall RR, 0.75; 95% CI, 0.68 to 0.83; NS RR, 0.67; 95% CI, 0.56 to 0.80); a significant increase of resectability rate (NS RR, 2.57; 95% CI, 1.76 to 3.74); a nonsignificant reduction of all-cause mortality (overall RR, 0.99; 95% CI, 0.94 to 1.05); and a significant increase of overdiagnosis rate (NS, 38%; 95% CI, 14 to 63). The analysis of lung cancer–related mortality by sex revealed nonsignificant differences between men and women ( P = .21; I-squared = 33.6%). CONCLUSION Despite there still being uncertainty about overdiagnosis estimate, this meta-analysis suggested that the CTLS benefits outweigh harms, in subjects with cigarette smoking history, ultimately supporting the systematic implementation of lung cancer screening worldwide.

Aim. Breast IRRADIATA (Italian Repository of RADIotherapy dATA) is a collaborative nationwide project supported by the Italian Society of Radiotherapy and Clinical Oncology (AIRO) and the Italian League Against Cancer (LILT). It focuses on breast cancer (BC) patients treated with radiotherapy (RT) and was developed to create a national registry and define the patterns of care in Italy. A dedicated tool for data collection was created and pilot tested. The results of this feasibility study are reported here. Methods. To validate the applicability of a user-friendly data collection tool, a feasibility study involving 17 Italian Radiation Oncology Centers was conducted from July to October 2021, generating a data repository of 335 BC patients treated between January and March 2020, with a minimum follow-up time of 6 months. A snapshot of the clinical presentation, treatment modalities and radiotherapy toxicity in these patients was obtained. A Data Entry Survey and a Satisfaction Questionnaire were also sent to all participants. Results. All institutions completed the pilot study. Regarding the Data Entry survey, all questions achieved 100% of responses and no participant reported spending more than 10 min time for either the first data entry or for the updating of follow-up. Results from the Satisfaction Questionnaire revealed that the project was described as excellent by 14 centers (82.3%) and good by 3 (17.7%). Conclusion. Current knowledge for the treatment of high-prevalence diseases, such as BC, has evolved toward patient-centered medicine, evidence-based care and real-world evidence (RWE), which means evidence obtained from real-world data (RWD). To this aim, Breast IRRADIATA was developed as a simple tool to probe the current pattern of RT care in Italy. The pilot feasibility of IRRADIATA encourages a larger application of this tool nationwide and opens the way to the assessment of the pattern of care radiotherapy directed to other cancers.

In recent years, hepato-pancreato-biliary (HPB) cancers have been increasing their incidence [...]

Purpose In the current study, we evaluated whether neoadjuvant chemoradiotherapy with reduced treatment volumes due to the exclusion of elective pelvic nodal irradiation is a feasible strategy for selected patients with locally advanced rectal cancer. Methods and Materials Patients with T2 low-lying/T3, N0-N1 rectal lesions without evidence of disease in the lateral lymph nodes were prospectively recruited. All patients underwent pretreatment testing, including computed tomography imaging of the chest, abdomen, and pelvis with intravenous contrast, pelvic magnetic resonance imaging with intravenous contrast, and 18-fluorodeoxyglucose positron emission/computed tomography. The clinical target volume included the primary tumor and the mesorectum with vascular supply containing the perirectal and presacral nodes, with the upper border at the S2/S3 interspace. The total radiation dose was 50.4 Gy, and fluoropyrimidine-based chemotherapy was associated concomitantly. The primary endpoint of the study was the reduction of gastrointestinal (GI) toxicity, and the secondary endpoints were pathologic complete response, local control, overall survival, and disease-free survival. Results Fifty-two patients (30 men, 22 women) with a median age of 67 years (range, 45-85 years) were enrolled in the study. Acute grade 3 GI toxicity was 7.6%, and there were no cases of grade 4 toxicity. Three patients (5.7%) developed a local recurrence. No relapse occurred in the lateral lymph nodes. The local control rate at 5 years was 96.1%. With a median follow-up time of 72.9 months (range, 2.5-127.6 months), the 3- and 5-year overall survival rates were 89.4% and 87%, respectively. The 3- and 5-year disease-free survival rates were 82.4% and 82.4%, respectively. Conclusions De-escalation of radiation therapy target volume reduces GI side effects without compromising efficacy in patients with rectal cancer. These results cannot be clearly extended to high-risk disease and need further evaluation in future randomized trials.

Background: Whole brain radiotherapy (WBRT) is a common treatment option for brain metastases secondary to non-small cell lung cancer (NSCLC). Data from the QUARTZ trial suggest that WBRT can be omitted in selected patients and treated with optimal supportive care alone. Nevertheless, WBRT is still widely used to treat brain metastases secondary to NSCLC. We analysed decision criteria influencing the selection for WBRT among European radiation oncology experts. Methods: Twenty-two European radiation oncology experts in lung cancer as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) for previous projects and by the Advisory Committee on Radiation Oncology Practice (ACROP) for lung cancer were asked to describe their strategies in the management of brain metastases of NSCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies. Results: Eight decision criteria (suitability for SRS, performance status, symptoms, eligibility for targeted therapy, extra-cranial tumour control, age, prognostic scores and "Zugzwang" (the compulsion to treat)) were identified. WBRT was recommended by a majority of the European experts for symptomatic patients not suitable for radiosurgery or fractionated stereotactic radiotherapy. There was also a tendency to use WBRT in the ALK/EGFR/ROS1 negative NSCLC setting. Conclusion: Despite the results of the QUARTZ trial WBRT is still widely used among European radiation oncology experts. Keywords: Decision tree; Decision-making; NSCLC; QUARTZ; WBRT.

To assess the tendencies of radiation oncologists (ROs) in adjusting radiotherapy treatments (RTH) according to the coronavirus disease 2019 (COVID-19) status of patients during the early severe acute respiratory syndrome coronavirus 2 (SARS-COV2) pandemic in Europe.An electronic survey was sent to 79 academic RTH departments across Europe. Only one respondent per institution was included. Respondents were asked how they would adjust RTH treatments based on COVID-19 status for more common cancers during the first wave of the pandemic. Respondents were also asked to report the number of external beam radiotherapy (EBRT) units and the number of new cases referred to their department. Descriptive statistical analysis was conducted focusing on different cancers.The overall response rate to the survey was 30.38% (24 institutions from 13 European countries). There was a wide range of different institutions regarding the number of patients, radiation oncologists, and facilities. A large proportion of respondents supported adjustment of RTH treatment (delay or switch to a shorter fractionation) for COVID-19-negative patients during the first wave of the pandemic only for early breast cancer (20% delay, 42.3% shorter), prostate cancer (53.6% delay, 21.4% shorter), and benign brain tumours (32% delay, 12% shorter). For COVID-19-negative patients with other cancers, most respondents recommended the standard RTH treatment. For COVID-19-positive patients, most respondents favoured a delay in RTH treatment or a shorter fractionation, regardless of cancer type and stage.The patient's COVID status significantly influenced the decision to undergo RTH treatment, regardless of the type and aggressiveness of cancer.

Treatment of stage III non-small cell lung cancer (NSCLC) has traditionally been controversial and challenging: multidisciplinary approach is mandatory and defining resectability is a critical issue; furthermore, patients are often frail due to age or comorbidities. After PACIFIC trial publication, a new therapeutic path has been defined for patients with unresectable NSCLC, with a prominent prognostic advantage. A trimodality treatment, with chemo-radiotherapy followed by maintenance durvalumab is now the standard of care, recommended by international guidelines. However, despite an impressive activity, the use of consolidative immunotherapy after concurrent chemoradiotherapy is highly debated in some clinically-relevant situations, including patients harboring EGFR mutations, older and/or frail patients not suitable for combined treatment, PD-L1 tumor expression. Here we report an expert virtual Italian meeting summary, where six medical oncologists and six radiation oncologists discussed all these aspects trying to underline the critical aspects and to find the possible clinical solutions.

Brain metastases (BMs) are common among patients affected by HER2+ metastatic breast cancer (>30%). The management of BMs is usually multimodal, including surgery, radiotherapy, systemic therapy and palliative care. Standard brain radiotherapy (RT) includes the use of stereotactic radiotherapy (SRT) for limited disease and whole brain radiotherapy (WBRT) for extensive disease. The latter is an effective palliative treatment but has a reduced effect on brain local control and BM overall survival, as it is also associated with severe neurocognitive sequelae. Recent advances both in radiation therapy and systemic treatment may change the paradigm in this subset of patients who can experience long survival notwithstanding BMs. In fact, in recent studies, SRT for multiple BM sites (>4) has shown similar efficacy when compared to irradiation of a limited number of lesions (one to three) without increasing toxicity. These findings, in addition to the introduction of new drugs with recognized intracranial activity, may further limit the use of WBRT in favor of SRT, which should be employed for treatment of both multiple-site BMs and for oligo-progressive brain disease. This review summarizes the supporting literature and highlights the need for optimizing combinations of the available treatments in this setting, with a particular focus on radiation therapy.

Simple Summary Brain metastases (BM) may affect a large portion of metastatic HER2-positive BC patients. Dual human epidermal growth factor receptor 2 (HER2) blockade with Pertuzumab and Trastuzumab (PT) in conjunction with chemotherapy represents the first line therapy of metastatic HER2- positive breast cancer (BC) and shows to prolong time to BM development as the first site of disease progression. When limited brain disease occurs with stable extracranial disease, current guidelines suggest to continue systemic therapies and add local brain treatment. However not data are available on the association between PT and stereotactic brain radiotherapy (SRT). This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and PT in patients with breast cancer BM. Abstract (1) Background: This study aims to assess the safety and efficacy of fractionated SRT (fSRT) and pertuzumab–trastuzumab (PT) in patients with breast cancer brain metastases (BCBM). (2) Methods: Patients with HER2+ BCBM who received FSRT from 2015 to 2019 were identified. Patients were included if they were treated with fSRT within 21 days of receiving PT. All lesions were treated with LINAC-based fSRT to a total dose of 27 Gy delivered in three consecutive fractions. All patients received concurrent PT. Patients were evaluated 4–6 weeks after SRS and subsequently every 2–3 months with MRI re-imaging (3) Results: A total of 49 patients with HER2+ brain metastases were identified. Of these patients, a total of 10 patients with 32 HER2+ BCBM were treated with concurrent SRT and PT and included in the analysis. No local progression was observed. Overall response rate was 68.7%. Only one patient developed asymptomatic radionecrosis. Median time to BM occurrence was 15.6 (range: 1–40.5 months). Distant intracranial failure occurred in 4/10 patients (40.0%). Overall BCBM median survival was 33.9 months (95%CI 24.1–43.6). Mean duration of PT treatment was 27.9 months (range: 10.1–53.7 months). (4) Conclusions: In our single institution experience, fSRT and PT showed to be a safe treatment for patients with BCBM with an adequate overall response rate.

The Italian Association of Medical Oncology (AIOM) and the Italian Association of Tumor Registries estimated about 41,500 new cases and 33,836 deaths from lung cancer in Italy in 2018,1 with a 5-year survival rate of 16% and a 10-year survival of 12% (11% for men and 15% for women). Currently, lung cancer represents the third most common neoplasm in the overall Italian population (Table 1), and it is the first cause of cancer death in men and the third in females (Table 2), with significant differences observed across the different Italian regions (Fig. 1).

In recent years, evidence has shown the potential therapeutic effects of different natural compounds for the prevention and treatment of radiotherapy-induced mucositis (RIOM). RIOM represents one of the most frequent side effects associated with anti-neoplastic treatments affecting patients’ quality of life and treatment response due to radiation therapy discontinuation. The innate radio-protective ability of natural products obtained from plants is in part due to the numerous antioxidants possessed as a part of their normal secondary metabolic processes. However, oxygen presence is a key point for radiation efficacy on cancer cells. The aim of this review is to describe the most recent evidence on radiation-induced injury and the emerging protective role of natural compounds in preventing and treating this specific damage without compromising treatment efficacy.

In March 2020, the World Health Organization (WHO) characterized the outbreak of the coronavirus disease 2019 (COVID-19) as a pandemic. The aim of this study was to evaluate the psychological impact of the COVID-19 pandemic on cancer patients undergoing radiotherapy. Were enrolled 210 patients in treatment and in follow-up who had access to the Radiation Oncology Department of the Campus Bio-Medico University Hospital Foundation between April and May 2020. The sample was subjected to structured interview and validated questionnaires. 37

Recent years have witnessed the rise of pathomics as a mean to describe histopathological images with quantitative biomarkers for predictive and prognostic ends, combining digital pathology, omic science and artificial intelligence. This novel research branch is the counterpart of radiomics which pursues the same aims extracting knowledge from radiological images. In this paper, we present the design of a pathomic deep learning-based system to predict the treatment outcome in non-small cell lung cancer patients. We describe the system design and optimization under the condition of limited data and limited training, with corresponding tests. The experimental results show the feasibility of the proposed scalable architecture providing also a comparison between different transfer learning strategies.

Objective To evaluate the early toxicity of concurrent use of radiotherapy in association with CDK4/6 inhibitors (palbociclib or ribociclib) in patients with hormone-receptors positive metastatic breast cancer. Material and methods Records of patients with histologically proven metastatic or locally advanced breast cancer treated in our institution were reviewed. Patients who received radiotherapy and concurrent palbociclib or ribociclib were selected. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE V4.0). Results Sixteen consecutive metastatic breast cancer patients with 24 radiotherapy treatments were studied. Thirteen patients (81.3%) received palbociclib, 3 (18.7%) patients received ribociclib concurrently with RT (18 and 5 radiotherapy courses respectively). The majority of patients (68.7%) received palliative radiotherapy to the bones (median dose 30 Gy, range 8–36 Gy). Five patients (31.2%) were treated in oligo-metastatic or oligo-progressive sites of disease with higher doses (median dose = 50 Gy, range 39.6–60 Gy). The most common toxicity observed was hematological toxicity. Neutropenia was common (grade 2 = 12.5%; grade 3 = 25%, grade 4 = 6.3%); 60% of patients experiencing grade ≥ 3 neutropenia had already experienced neutropenia during previous cycles of palbociclib. One patient (6.3%) completed the RT course earlier (48 Gy of 50 Gy prescribed) and another patient (6.3%) suspended RT for 2 days. Conclusion concomitant treatment of CDK4/6 and radiotherapy seems well tolerated; high grade hematological toxicity is common, but did not change treatment course in the majority of patients. Previous toxicity should be carefully evaluated as it usually reoccurs.

Background: Due to conflicting results between major trials the role of prophylactic cranial irradiation (PCI) in stage IV small cell lung cancer (SCLC) is controversial.Methods: We obtained a list of 13 European experts from both the European Society for Therapeutic Radiation Oncology (ESTRO) and the International Association for the Study of Lung Cancer (IASLC). The strategies in decision making for PCI in stage IV SCLC were collected. Decision trees were created representing these strategies. Analysis of consensus was performed with the objective consensus methodology.Results: The factors associated with the recommendation for the use of PCI included the fitness of the patient, young age and good response to chemotherapy. PCI was recommended by the majority of experts for non-elderly fit patients who had at least a partial response (PR) to chemotherapy (for complete remission (CR) 85% of radiation oncologists and 69% of medical oncologists, for PR: 85% of radiation oncologists and 54% of medical oncologists). For patients with stable disease after chemotherapy, PCI was recommended by 6 out of 13 (46%) radiation oncologists and only 3 out of 13 medical oncologists (23%). For elderly fit patients with CR, a majority recommended PCI (62%) and no consensus was reached for patients with PR.Conclusion: European radiation and medical oncologists specializing in lung cancer recommend PCI in selected patients and restrict its use primarily to fit, non-elderly patients who responded to chemotherapy. (C) 2018 Elsevier B.V. All rights reserved.

Non-small cell lung cancer (NSCLC) is diagnosed in about 30% of patients as locally advanced disease (stage III) which is defined as a tumour that exceeds the structures of the lung itself, but without clinical evidence of distant spreading. These patients form a highly heterogeneous group with controversial treatment based on the combination of surgery, chemotherapy and radiotherapy (1).

Over the past century, technologic advances have promoted the evolution of radiation therapy into a precise treatment modality allowing for the maximal administration of dose to tumors while sparing normal tissues. In parallel with this technological maturation, the rapid expansion in understanding the basic biology and heterogeneity of cancer has led to the development of several compounds that target specific pathways. Many of them are in advanced steps of clinical development for combination treatments with radiotherapy, and can be incorporated into radiation oncology practice for a personalized approach to maximize the therapeutic gain. This review describes the rationale for combining novel agents with radiation, and provides an overview of the current landscape focused on treatment efficacy.