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Cyrus Chargari - Top 30 Publications

Dose-volume effects in pathologic lymph nodes in locally advanced cervical cancer.

In cervical cancer patients, dose-volume relationships have been demonstrated for tumor and organs-at-risk, but not for pathologic nodes. The nodal control probability (NCP) according to dose/volume parameters was investigated.

Concerns about cardiotoxicity in the HERA trial.

Brachytherapy for conservative treatment of invasive penile carcinoma in older patients: Single institution experience.

No study has examined the possibility to perform an organ sparing strategy in older patients with penile carcinoma, and amputation is frequently proposed. We report our experience of interstitial brachytherapy for the conservative treatment of penile carcinoma confined to the glans in patients aged of 70years and more.

Clinical trials and perspectives of radiotherapy for uterine endometrial cancers.

The adjuvant management of uterine endometrial cancer has been studied in many randomized trials, leading to define postoperative therapeutic indications, depending on the risk factors for relapse, and on the expected benefit in terms of locoregional control and survival. The potential toxicity of treatments should be also considered. We review the available literature that yielded to guidelines that were recently published, on behalf of European societies, and we highlight the perspectives on ongoing studies, aimed at better defining the place and type of adjuvant treatment.

Long-term evaluation of urinary, sexual, and quality of life outcomes after brachytherapy for penile carcinoma.

Brachytherapy (BT) is an effective organ-preserving treatment for selected localized penile carcinoma, providing high local control rates. Long-term functional results however, are still insufficiently evaluated.

A score combining baseline neutrophilia and primary tumor SUVpeak measured from FDG PET is associated with outcome in locally advanced cervical cancer.

We investigated whether a score combining baseline neutrophilia and a PET biomarker could predict outcome in patients with locally advanced cervical cancer (LACC).

Radiation induced gastroparesis-case report and literature review.

Radiation induced gastroparesis as well as the other autonomic nervous system radiation induced neuropathies are poorly described in the literature. A case of gastroparesis associated with phrenic and recurrent laryngeal nerves paralysis was observed in a 69-year old patient. She was already treated two times by rachis radiotherapy in a context of breast cancer with bone metastases. Anatomical and chronological correlation of lesions, concomitant nerve damage in the radiation fields and elimination of the main differential diagnoses allowed us to link this case of gastroparesis with the background of radiotherapy. It confirms the role of vagus nerve lesion in radiation induced gastroparesis. This specific diagnosis led to a successful treatment and a quality of life improvement.

Flattening Filter Free vs. Flattened Beams for Lung Stereotactic Body Radiation Therapy.

To assess the clinical impact of high dose rate stereotactic body radiation therapy (SBRT) in patients with lung neoplastic lesions.

Neutrophils, a candidate biomarker and target for radiation therapy?

Neutrophils are the most abundant blood-circulating white blood cells, continuously generated in the bone marrow. Growing evidence suggests they regulate the innate and adaptive immune system during tumor evolution. This review will first summarize the recent findings on neutrophils as a key player in cancer evolution, then as a potential biomarker, and finally as therapeutic targets, with respective focuses on the interplay with radiation therapy. A complex interplay: Neutrophils have been associated with tumor progression through multiple pathways. Ionizing radiation has cytotoxic effects on cancer cells, but the sensitivity to radiation therapy in vivo differ from isolated cancer cells in vitro, partially due to the tumor microenvironment. Different microenvironmental states, whether baseline or induced, can modulate or even attenuate the effects of radiation, with consequences for therapeutic efficacy. Inflammatory biomarkers: Inflammation-based scores have been widely studied as prognostic biomarkers in cancer patients. We have performed a large retrospective cohort of patients undergoing radiation therapy (1233 patients), with robust relationship between baseline blood neutrophil count and 3-year's patient's overall survival in patients with different cancer histologies. (Pearson's correlation test: p = .001, r = -.93). Therapeutic approaches: Neutrophil-targeting agents are being developed for the treatment of inflammatory and autoimmune diseases. Neutrophils either can exert antitumoral (N1 phenotype) or protumoral (N2 phenotype) activity, depending on the Tumor Micro Environment. Tumor associated N2 neutrophils are characterized by high expression of CXCR4, VEGF, and gelatinase B/MMP9. TGF-β within the tumor microenvironment induces a population of TAN with a protumor N2 phenotype. TGF-β blockade slows tumor growth through activation of CD8 + T cells, macrophages, and tumor associated neutrophils with an antitumor N1 phenotype.

Pulsed-dose rate brachytherapy for pediatric bladder prostate rhabdomyosarcoma: Compliance and early clinical results.

No data are available on the feasibility of pulsed dose rate (PDR) brachytherapy in very young children. Our experience of PDR brachytherapy for bladder prostate (BP) rhabdomyosarcoma (RMS) is reported, with focus on compliance and dosimetric parameters.

Clinical outcomes after interstitial brachytherapy for early-stage nasal squamous cell carcinoma.

Radiotherapy of nasal carcinomas results in cure rates comparable to surgery, with anatomic preservation and good cosmesis. Brachytherapy (BT) overcomes difficulties with dosimetric coverage and affords a localized and highly conformal irradiation. We report our experience of BT for early-stage nasal squamous cell carcinomas (SCCs).

Radiotherapy among nonagenarians with anal or rectal carcinoma: should we avoid or adapt treatment?

Brain metastases from non-small cell lung carcinoma: Changing concepts for improving patients' outcome.

The management of Non Small Cell Lung Cancer (NSCLC) brain metastases is challenging, as this frequent complication negatively impacts patients' quality of life, and can be a life-threatening event. Through a review of the literature, we discuss the main therapeutic options and the recent developments that improved (and complicated) the management of NSCLC brain metastases patients. Most current validated approaches are local with exclusive or combined surgery, whole brain radiotherapy (WBRT) and stereotactic radiotherapy (SRT). At the same time, there is a growing role for systemic treatments that might significantly postpone WBRT. Targeted therapies efficacy/toxicity profile remains to be defined but predictive and prognostic molecular factors integration could help to select treatments fully adapted to life expectancy and progression risk.

Diffusion-weighted MRI in image-guided adaptive brachytherapy: Tumor delineation feasibility study and comparison with GEC-ESTRO guidelines.

To examine the feasibility of using diffusion-weighted images (DWIs) coregistered with T2-weighted (T2w) sequence in treatment planning system to improve target delineation for image-guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer patients.

External validation of leukocytosis and neutrophilia as a prognostic marker in anal carcinoma treated with definitive chemoradiation.

To validate the prognostic value of leukocyte disorders in anal squamous cell carcinoma (SCC) patients receiving definitive concurrent chemoradiation.

The MET/AXL/FGFR Inhibitor S49076 Impairs Aurora B Activity and Improves the Antitumor Efficacy of Radiotherapy.

Several therapeutic agents targeting HGF/MET signaling are under clinical development as single agents or in combination, notably with anti-EGFR therapies in non-small cell lung cancer (NSCLC). However, despite increasing data supporting a link between MET, irradiation, and cancer progression, no data regarding the combination of MET-targeting agents and radiotherapy are available from the clinic. S49076 is an oral ATP-competitive inhibitor of MET, AXL, and FGFR1-3 receptors that is currently in phase I/II clinical trials in combination with gefitinib in NSCLC patients whose tumors show resistance to EGFR inhibitors. Here, we studied the impact of S49076 on MET signaling, cell proliferation, and clonogenic survival in MET-dependent (GTL16 and U87-MG) and MET-independent (H441, H460, and A549) cells. Our data show that S49076 exerts its cytotoxic activity at low doses on MET-dependent cells through MET inhibition, whereas it inhibits growth of MET-independent cells at higher but clinically relevant doses by targeting Aurora B. Furthermore, we found that S49076 improves the antitumor efficacy of radiotherapy in both MET-dependent and MET-independent cell lines in vitro and in subcutaneous and orthotopic tumor models in vivo In conclusion, our study demonstrates that S49076 has dual antitumor activity and can be used in combination with radiotherapy for the treatment of both MET-dependent and MET-independent tumors. These results support the evaluation of combined treatment of S49076 with radiation in clinical trials without patient selection based on the tumor MET dependency status. Mol Cancer Ther; 16(10); 2107-19. ©2017 AACR.

Prediction of cervical cancer recurrence using textural features extracted from 18F-FDG PET images acquired with different scanners.

To identify an imaging signature predicting local recurrence for locally advanced cervical cancer (LACC) treated by chemoradiation and brachytherapy from baseline 18F-FDG PET images, and to evaluate the possibility of gathering images from two different PET scanners in a radiomic study.

Locally advanced cervical cancer: Is it relevant to report image-guided adaptive brachytherapy using point A dose?

To evaluate the usefulness of reporting the point A dose in patients with locally advanced cervical cancer treated with image-guided adaptive brachytherapy (IGABT).

Assessment of the novel online delineation workshop dummy run approach using FALCON within a European multicentre trial in cervical cancer (RAIDs).

Online delineation workshops (ODW) permit training of geographically dispersed participants. The purpose is to evaluate the methodology of an ODW using FALCON to harmonize delineation within a European multicentre trial on locally advanced cervical cancer (LACC).

Brachytherapy for Conservative Treatment of Invasive Penile Carcinoma: Prognostic Factors and Long-Term Analysis of Outcome.

To report the largest experience with brachytherapy as a conservative approach for the treatment of penile carcinoma.

Brachytherapy Combined With Surgery for Conservative Treatment of Children With Bladder Neck and/or Prostate Rhabdomyosarcoma.

To report the results of a conservative strategy based on partial surgery combined with brachytherapy in a prospective cohort of children with bladder-prostate rhabdomyosarcoma (BP RMS).

Inflammatory bowel diseases activity in patients undergoing pelvic radiation therapy.

Few studies with contradictory results have been published on the safety of pelvic radiation therapy (RT) in patients with inflammatory bowel disease (IBD).

Optimizing Local Control in High-Grade Uterine Sarcoma: Adjuvant Vaginal Vault Brachytherapy as Part of a Multimodal Treatment.

The phase III European Organization for Research and Treatment of Cancer 55874 study has shown that external beam radiotherapy (EBRT) given as adjuvant treatment decreased locoregional recurrences from 40% to 20% in patients (pts) with localized uterine sarcomas (US). No data exist, however, on the place of brachytherapy (BT).

Contribution of image-guided adaptive brachytherapy to pelvic nodes treatment in locally advanced cervical cancer.

With the increasing use of simultaneous integrated boost in the treatment of cervical cancer, there is a need to anticipate the brachytherapy (BT) contribution at the level of the pathologic pelvic lymph nodes. This study aimed to report the dose delivered at their level during BT.

In Regard to Swanick et al.

Melanoma: Last call for radiotherapy.

Melanoma is traditionally considered to be a radioresistant tumor. However, radiotherapy and immunotherapy latest developments might upset this radiobiological dogma. Stereotactic radiotherapy allows high dose per fraction delivery, with high dose rate. More DNA lethal damages, less sublethal damages reparation, endothelial cell apoptosis, and finally clonogenic cell dysfunction are produced, resulting in improved local control. Radiotherapy can also enhance immune responses, inducing neoantigens formation, tumor antigen presentation, and cytokines release. A synergic effect of radiotherapy with immunotherapy is expected, and might lead to abscopal effects. If hadrontherapy biological properties seem able to suppress hypoxia-induced radioresistance and increase biological efficacy, ballistic advantages over photon radiations might also improve radiotherapy outcomes on usually poor prognosis locations. The present review addresses biological and clinical effects of high fraction dose, bystander effect, abscopal effect, and hadrontherapy features in melanoma. Clinical trials results are warranted to establish indications of innovative radiotherapy in melanoma.

Outcome of early stage cervical cancer patients treated according to a radiosurgical approach: Clinical results and prognostic factors.

To report clinical results of a multimodal strategy based on preoperative brachytherapy followed with surgery in early stage cervical cancer.

Leukocytosis and neutrophilia predict outcome in locally advanced esophageal cancer treated with definitive chemoradiation.

To investigate the prognostic value of leukocyte and neutrophil count as biomarkers in patients with locally advanced esophageal squamous cell carcinoma (SCC) undergoing exclusive chemoradiation.

Leukocytosis and neutrophilia predicts outcome in anal cancer.

Leukocytosis and neutrophilia could be the tip of the iceberg in the inflammatory tumor microenvironment. We aimed to validate their prognostic significance in a cohort of patients treated with definitive chemoradiation for anal squamous cell carcinoma (SCC).

Neutrophilia in locally advanced cervical cancer: A novel biomarker for image-guided adaptive brachytherapy?

To study the prognostic value of leucocyte disorders in a prospective cohort of cervical cancer patients receiving definitive chemoradiation plus image-guided adaptive brachytherapy (IGABT).