Clinical applications of stereotactic radiation therapy for oligometastatic cancer patients: a disease-oriented approach

Oligometastases from solid tumors are currently recognized as a distinct clinical entity, corresponding to an intermediate state between local and widespread disease. It has been suggested that local ablative therapies (including surgery, radiofrequency ablation and radiation therapy) play an important role in this setting, in combination or not with systemic therapies, particularly in delaying disease progression and hopefully in increasing the median survival time. Stereotactic body radiation therapy (SBRT) rapidly emerged in recent years as one of the most effective and less toxic local treatment modalities for lung, liver, adrenal, brain and bone metastases. The aim of this review was to focus on its clinical role for oligometastatic disease in four major cancer subtypes: lung, breast, colorectal and prostate. On the basis of the available evidence, SBRT is able to provide high rates of local tumor control without significant toxicity. Its global impact on survival is uncertain; however, in specific subpopulations of oligometastatic patients there is a trend towards a significant improvement in progression-free and overall survival rates; these important data might be used as a platform for clinical decision-making and establish the basis for the current and future prospective trials investigating its role with or without systemic treatments

Role of Modern Radiation Therapy in Early Stage Hodgkin's Lymphoma: a Young Radiation Oncologists' Perspective

The role of radiotherapy is well established in combined modality programs for early stage Hodgkin's lymphoma, but still debated with regards to late toxicity issues. Modern radiotherapy prescribing attitudes include lower doses and smaller fields, together with the implementation of sophisticated and dedicated delivery techniques. Aim of this review is to briefly discuss the current role of radiotherapy in this field and the potential future developments. Major trials conducted in recent years in early stage Hodgkin's lymphoma are critically reviewed and discussed with a focus on radiotherapy-related issues and with an attention to current treatment options by a “young” radiation oncologists’ perspective

Stereotactic radiotherapy for early stage non-small cell lung cancer

Stereotactic body radiotherapy (SBRT) represents a consolidated treatment option for patients with medically inoperable early stage non-small cell lung cancer (NSCLC). The clinical evidence accumulated in the past decade supports its use as an alternative to surgery with comparable survival outcomes. Due to its limited toxicity, SBRT is also applicable to elderly patients with very poor baseline pulmonary function or other severe comorbidities. Recent comparative studies in operable patients raised the issue of the possible use of SBRT also for this subgroup, with quite promising results that still should be fully confirmed by prospective trials with long-term follow-up. Aim of this review is to summarize and discuss the major studies conducted over the years on SBRT and to provide data on the efficacy and toxicity of this radiotherapy technique for stage I NSCLC. Technical aspects and quality of life related issues are also discussed, with the goal to provide information on the current role and limitations of SBRT in clinical practice

Is clinical radiosensitivity a complex genetically controlled event?

New insights into molecular mechanisms responsible for cellular radiation response are coming from recent basic radiobiological studies. Preliminary data supporting the concept of clinical radiosensitivity as a complex genetically controlled event are available, and it seems reasonable to hypothesize that genes encoding for proteins implicated in known radiation-induced pathways, such as DNA repair, could influence normal tissue and tumor response to radiotherapy. Such genes could be considered as candidates for experimental studies and as targets for innovative therapies. Variants that could influence individual radiosensitivity have been recently identified, and specific Single Nucleotide Polymorphisms have been associated to the development of different radiation effects on normal tissues. Allelic architecture of complex traits able to modify phenotypes is difficult to be established, and different grades of interaction between common or rare genetic determinants may be present and should be considered. Many different experimental strategies could be investigated in the future, such as analysis of multiple genes in large irradiated patient cohorts strictly observed for radiation effects or identification of new candidate genes, with the aim of identifying factors that could be employed in predictive testing and individualization of radiation therapy on a genetic basis

Peripheral blood complete remission after splenic irradiation in Mantle-Cell Lymphoma with 11q22-23 deletion and ATM inactivation

Mantle Cell Lymphoma (MCL) is a well-known histological and clinical subtype of B-cell non-Hodgkin's Lymphomas. It is usually characterized by an aggressive disease course, presenting with advanced stage disease at diagnosis and with low response rates to therapy. However few cases of indolent course MCL have been described. We herein report a case of MCL with splenomegaly and peripheral blood involvement as main clinical features. The patient underwent moderate dose splenic radiation therapy and achieved spleen downsizing and peripheral blood complete remission. Splenic irradiation has been extensively used in the past as palliative treatment in several lymphoproliferative disorders and a systemic effect and sometimes peripheral blood complete remissions have been observed. Mainly advocated mechanisms responsible for this phenomenon are considered direct radiation-induced apoptotic cell death, immune modulation via proportional changes of lymphocyte subsets due to known differences in intrinsic radiosensitivity and a radiation-induced cytokine release. The peculiar intrinsic radiosensitivity pattern of lymphoid cells could probably be explained by well-defined individual genetic and molecular features. In this context, among NHLs, MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated) inactivation. While the ATM gene is thought to play a key-role in detecting radiation-induced DNA damage (expecially Double Strand Breaks), recent in vitro data support the hypothesis that ATM loss may actually contribute to the radiosensitivity of MCL cells. ATM status was retrospectively investigated in our patient, with the tool of Fluorescence In Situ Hybridization, showing a complete inactivation of a single ATM allele secondary to the deletion of chromosomal region 11q22-23. The presence of this kind of cytogenetic aberration may be regarded in the future as a potential predictive marker of radiation response

Role of modern radiation therapy in early stage Hodgkin's lymphoma: A young radiation oncologists’ perspective

The role of radiotherapy is well established in combined modality programs for early stage Hodgkin's lymphoma, but still debated with regards to late toxicity issues. Modern radiotherapy prescribing attitudes include lower doses and smaller fields, together with the implementation of sophisticated and dedicated delivery techniques. Aim of this review is to briefly discuss the current role of radiotherapy in this field and the potential future developments. Major trials conducted in recent years in early stage Hodgkin's lymphoma are critically reviewed and discussed with a focus on radiotherapy-related issues and with an attention to current treatment options by a “young” radiation oncologists’ perspective

Locally-advanced non-small cell lung cancer: Shall immunotherapy be a new chance?

Locally advanced non-small cell lung cancer (NSCLC) represents approximately one third of presentations at diagnosis. Most patients are judged non-surgical due to disease extension, and chemo-radiotherapy still represents the standard therapeutic option, with unsatisfactory results in terms of overall survival (OS) despite advances in staging and radiation therapy planning and delivery. Immunotherapy, and in particular immune-checkpoint inhibitors targeting the PD-1/PD-L1 axis, gained wide popularity for NSCLC in light of the positive findings of several trials in metastatic disease. Stage III unresectable NSCLC is a remarkably interesting setting for the combined use of chemo-radiation and immunotherapy, also considering the multiple experimental evidences in favor of a synergistic effect between radiation and immune checkpoint inhibitors, with the potential of enhancing immuno-modulating effects and overcoming resistance. We here summarized the biological rationale and the initial clinical experiences testing for this combination, and we briefly discussed ongoing trials and future options in this field