Publications by authors named "Aron Popovtzer"

71 Publications

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma.

Oncology 2021 Mar 31:1-7. Epub 2021 Mar 31.

Department of Pathology, Hadassah Hebrew University Medical Center, Jerusalem, Israel.

Introduction: Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study's main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings.

Materials And Methods: This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies.

Results: We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65-0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity.

Discussion And Conclusions: Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.
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http://dx.doi.org/10.1159/000515441DOI Listing
March 2021

COVID-19 vaccine as a cause for unilateral lymphadenopathy detected by 18F-FDG PET/CT in a patient affected by melanoma.

Eur J Nucl Med Mol Imaging 2021 Mar 6. Epub 2021 Mar 6.

Sharett Institute of Oncology, Hadassah Medical Center, The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel.

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http://dx.doi.org/10.1007/s00259-021-05278-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936232PMC
March 2021

Chemotherapy-induced acute vascular injury involves intracellular generation of ROS via activation of the acid sphingomyelinase pathway.

Cell Signal 2021 Jun 26;82:109969. Epub 2021 Feb 26.

Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. Electronic address:

Several categories of chemotherapy confer substantial risk for late-term vascular morbidity and mortality. In the present study, we aimed to investigate the mechanism of acute chemotherapy-induced vascular injury in normal tissues. Specifically, we looked at activation of the acid sphingomyelinase (ASMase)/ceramide pathway, which leads to generation of reactive oxygen species (ROS) and induction of oxidative stress that may result in vascular injury. In particular, we focused on two distinct drugs, doxorubicin (DOX) and cisplatin (CIS) and their effects on normal endothelial cells. In vitro, DOX resulted in increased ASMase activity, intra-cellular ROS production and induction of apoptosis. CIS treatment generated significantly reduced effects in endothelial cells. In-vivo, murine femoral arterial blood flow was measured in real-time, during and after DOX or CIS administration, using fluorescence optical imaging system. While DOX caused constriction of small vessels and disintegration of large vessels' wall, CIS induced minor vascular changes in arterial blood flow, correlating with the in vitro findings. These results demonstrate that DOX induces acute vascular injury by increased ROS production, via activation of ASMase/ceramide pathway, while CIS increases ROS production and its immediate extracellular translocation, without causing detectable acute vascular injury. Our findings may potentially lead to the development of new strategies to prevent long-term cardiovascular morbidity in cancer survivors.
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http://dx.doi.org/10.1016/j.cellsig.2021.109969DOI Listing
June 2021

The potential of somatostatin receptor 2 as a novel therapeutic target in salivary gland malignant tumors.

J Cancer Res Clin Oncol 2021 May 17;147(5):1335-1340. Epub 2021 Feb 17.

Department of Otolaryngology, Hadassah University Hospital, P.O. Box 12000, 91120, Jerusalem, Israel.

Background: Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined.

Methods: In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016.

Results: Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant.

Conclusion: This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.
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http://dx.doi.org/10.1007/s00432-021-03538-1DOI Listing
May 2021

'Golden' exosomes as delivery vehicles to target tumors and overcome intratumoral barriers: in vivo tracking in a model for head and neck cancer.

Biomater Sci 2021 Mar 21;9(6):2103-2114. Epub 2021 Jan 21.

Department of Otolaryngology, Head and Neck Surgery, Kaplan Medical Center, Rehovot, Israel, affiliated to the Hebrew University, Jerusalem, Israel.

Exosomes are promising vectors for anti-tumor therapy, due to their biocompatibility, low immunogenicity, and innate ability to interact with target cells. However, promoting clinical application of exosome-based therapeutics requires elucidation of key issues, including exosome biodistribution, tumor targeting and accumulation, and the ability to overcome tumor barriers that limit the penetration of various nano-carriers and drugs. Here, we examined these parameters in exosomes derived from mesenchymal stem cells (MSC-exo) and from the A431 squamous cell carcinoma line (A431-exo), which both have potential use in cancer therapy. Using our novel technique combining gold nanoparticle (GNP) labeling of exosomes and non-invasive computed tomography imaging (CT), we longitudinally and quantitatively tracked the two intravenously-injected exosome types in A431 tumor-bearing mice. CT imaging up to 48 h and subsequent ex vivo analysis revealed tumor homing abilities of both exosome types, yet there was significantly higher tumor accumulation of MSC-exo as compared to A431-exo. Moreover, MSC-exo demonstrated the ability to penetrate the tumor and distribute throughout its bulk, while non-encapsulated GNPs remained concentrated at the tumor periphery. Histological analysis showed penetration of MSC-exo not only into the tumor tissue, but also into tumor cell cytoplasm. While the proportion of biodistribution between organs at 48 h was similar for both exosome types, more rapid clearance was indicated for A431-exo. Thus, our findings demonstrate an effect of exosome type on tumor targeting abilities and biodistribution, and suggest that MSC-exo may have superior abilities for tumor-targeted therapy.
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http://dx.doi.org/10.1039/d0bm01735cDOI Listing
March 2021

Prophylactic Topical Treatment for EGFR Inhibitor-Induced Papulopustular Rash: A Randomized Clinical Trial.

Dermatology 2020 Dec 30:1-7. Epub 2020 Dec 30.

Institute of Oncology, Davidoff Cancer Center, Petah Tikva, Israel.

Background: The incidence of epidermal growth factor receptor inhibitor (EGFRI)-induced papulopustular rash is 60-85%.

Objective: To investigate prophylactic topical treatment for EGFRI-induced rash.

Methods: A single-center, randomized, double-blind, placebo-controlled trial. Adult cancer patients initiating treatment with EGFRIs were randomized to receive facial topical treatment with chloramphenicol 3% + prednisolone 0.5% (CHL-PRED) ointment, chloramphenicol 3% (CHL) ointment, or aqua cream (AQUA). The primary end points were the incidence of ≥grade 3 rash using the Common Terminology Criteria for Adverse Events (CTCAE), on days 14 and 30. A subanalysis was conducted for incidence of a protocol-specified significant rash, defined as ≥10 facial papulopustular lesions.

Results: The per-protocol analysis on day 14 included 69 patients, who received CHL-PRED (21), CHL (23), or AQUA (25). The incidence of CTCAE ≥grade 3 rash was not statistically significant between arms; however, the incidence of the protocol-specified significant rash was: CHL-PRED 14%, CHL 39%, and AQUA 48% (p = 0.03, CHL-PRED vs. AQUA). At 30 days, the CTCAE ≥grade 3 incidence was similar, but the incidences of protocol-specified significant rash were 6%, 16%, and 43% (p = 0.03, CHL-PRED vs. AQUA). No significant differences were found between CHL and CHL-PRED and between CHL and AQUA.

Conclusions: Prophylactic topical CHL-PRED was efficacious when compared to AQUA, in the treatment of EGFRI-induced facial papulopustular rash.
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http://dx.doi.org/10.1159/000511869DOI Listing
December 2020

Glucose-Functionalized Liposomes for Reducing False Positives in Cancer Diagnosis.

ACS Nano 2021 01 24;15(1):1301-1309. Epub 2020 Dec 24.

Faculty of Engineering and the Institute of Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat Gan 5290002, Israel.

Fluorodeoxyglucose-positron emission tomography (F-FDG-PET) is a powerful tool for cancer detection, staging, and follow-up. However, F-FDG-PET imaging has high rates of false positives, as it cannot distinguish between tumor and inflammation regions that both feature increased glucose metabolic activity. In the present study, we engineered liposomes coated with glucose and the chelator dodecane tetraacetic acid (DOTA) complexed with copper, to serve as a diagnostic technology for differentiating between cancer and inflammation. This liposome technology is based on FDA-approved materials and enables complexation with metal cations and radionuclides. We found that these liposomes were preferentially uptaken by cancer cell lines with high metabolic activity, mediated via glucose transporter-1. In vivo, these liposomes were avidly uptaken by tumors, as compared to liposomes without glucose coating. Moreover, in a combined tumor-inflammation mouse model, these liposomes accumulated in the tumor tissue and not in the inflammation region. Thus, this technology shows high specificity for tumors while evading inflammation and has potential for rapid translation to the clinic and integration with existing PET imaging systems, for effective reduction of false positives in cancer diagnosis.
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http://dx.doi.org/10.1021/acsnano.0c08530DOI Listing
January 2021

Solid organ transplantation worsens the prognosis of patients with cutaneous squamous cell carcinoma of the head and neck region-Comparison between solid organ transplant recipients and immunocompetent patients.

Head Neck 2021 Mar 27;43(3):884-894. Epub 2020 Nov 27.

Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petah Tikva, Israel.

Background: Cutaneous squamous cell carcinoma of the head and neck (CSCC-HN) appears to behave more aggressively in immunosuppressed patients. We aimed to investigate this hypothesis by comparing solid organ transplant recipients (SOTR) with CSCC-HN to immunocompetent patients.

Methods: A retrospective comparative study was conducted for SOTR and immunocompetent patients who were treated for CSCC-HN.

Results: A total of 177 SOTR and 157 immunocompetent patients with CSCC-HN were included. Lymph node metastases were more common in the SOTR group (9% vs 3%), and distant metastases occurred only in SOTR (3% of patients). SOTR had a higher rate of recurrences (19% vs 10%), which were mostly regional (7%) and distant (3%). The 2-year disease-specific survival of SOTR was lower (93% vs 100%).

Conclusions: SOTR with CSCC-HN has significantly worse outcomes compared to immunocompetent patients. Solid-organ transplantation should be regarded as a negative prognostic factor in patients with CSCC-HN.
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http://dx.doi.org/10.1002/hed.26546DOI Listing
March 2021

CDK 4/6 Inhibition Overcomes Acquired and Inherent Resistance to PI3Kα Inhibition in Pre-Clinical Models of Head and Neck Squamous Cell Carcinoma.

J Clin Med 2020 Oct 7;9(10). Epub 2020 Oct 7.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

Activating alterations in , the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in head and neck squamous cell carcinoma (HNSCC) and thought to be one of the main drivers of these tumors. However, early clinical trials on PI3K inhibitors (PI3Ki) have been disappointing due to the limited durability of the activity of these drugs. To investigate the resistance mechanisms to PI3Ki and attempt to overcome them, we conducted a molecular-based study using both HNSCC cell lines and patient-derived xenografts (PDXs). We sought to simulate and dissect the molecular pathways that come into play in PIK3CA-altered HNSCC treated with isoform-specific PI3Ki (BYL719, GDC0032). In vitro assays of cell viability and protein expression indicate that activation of the mTOR and cyclin D1 pathways is associated with resistance to PI3Ki. Specifically, in BYL719-resistant cells, BYL719 treatment did not induce pS6 and pRB inhibition as detected in BYL719-sensitive cells. By combining PI3Ki with either mammalian target of rapamycin complex 1 (mTORC1) or cyclin D1 kinase (CDK) 4/6 specific inhibitors (RAD001 and abemaciclib, respectively), we were able to overcome the acquired resistance. Furthermore, we found that PI3Ki and CDK 4/6 inhibitors have a synergistic anti-tumor effect when combined in human papillomavirus (HPV)-negative/PIK3CA-WT tumors. These findings provide a rationale for combining PI3Ki and CDK 4/6 inhibitors to enhance anti-tumor efficacy in HNSCC patients.
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http://dx.doi.org/10.3390/jcm9103214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601167PMC
October 2020

Supraglottic Carcinoma in Intravenous Opioid Drug Abusers: A Distinct Disease with Improved Survival.

Laryngoscope 2021 04 18;131(4):E1190-E1197. Epub 2020 Sep 18.

Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objectives/hypothesis: Recent evidence indicates an increased prevalence of intravenous opioid drug abusers (IVDAs) among supraglottic squamous cell carcinoma (SG-SCC) patients. This study investigates whether the clinical course of SG-SCC in IVDA differs from SG-SCC in non-IVDA.

Study Design: A retrospective case-control study conducted in a in two tertiary referral centers.

Methods: This case-control study compares IVDA with non-IVDA patients diagnosed and treated for SG-SCC in between 2005 and 2018. Disease-free survival (DFS) and overall survival (OS) were calculated using the Kaplan-Meier estimator. Adjusted odds ratios (ORs) for mortality were calculated using multivariant analyses.

Results: A total of 124 patients were included; 21% (26) were IVDA, and 79% (98) were non-IVDA. Age at diagnosis in the IVDA group versus the non-IVDA group was 53 and 66 years, respectively (P = .001). Nevertheless, the age hazard ratio for OS was calculated and found to have minimal to no effect, 1.05 (95% Cl: 1.025-1.076). Otherwise, the two groups were comparable regarding demographics, other risk factors (i.e., gender, smoking, and alcohol), and comorbidities status, as well as the comparable stage at diagnosis, histologic grading, and treatment modalities. Although the DFS was comparable in both groups, the 5-year OS was 55% in the IVDA group compared with 34% among the non-IVDA patients (P = .04). In multivariant analyses for mortality, positive IVDA history was found to be protective, adjusted OR: 0.263 (95% CI: 0.081-0.854). Similarly, within the subgroup of 100 patients with advanced-stage disease (III and IV), the adjusted OR was 0.118 (95% CI: 0.028-0.495).

Conclusions: SG-SCC in IVDA patients has a distinct clinical course, presenting at a younger age, and may have improved prognosis.

Level Of Evidence: NA Laryngoscope, 131:E1190-E1197, 2021.
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http://dx.doi.org/10.1002/lary.29067DOI Listing
April 2021

Induction chemotherapy for locally advanced laryngeal and hypopharyngeal cancer: Single institution experience.

Head Neck 2020 11 16;42(11):3118-3124. Epub 2020 Jul 16.

Institute of Oncology, Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.

Background: The role of induction chemotherapy (IC) in locally-advanced head and neck squamous cell carcinoma (LAHNSCC) is unclear.

Methods: A retrospective study of 104 patients with LAHNSCC of the larynx and hypopharynx, treated with IC or up-front chemoradiotherapy (CRT).

Results: Eighty patients received CRT and 24 IC followed by CRT; median follow up was 51.33 months. IC significantly improved median overall survival (OS) in the hypopharyngeal cancer group (64.7 vs 21 months, P = .003); with significant difference in the proportion of complete response at first imaging assessment post definitive CRT; no significant difference in disease free survival (DFS), loco-regional or distant failure in the hypopharyngeal cancer group; or OS and DFS in the laryngeal cancer group. Patients with laryngeal cancer had significantly better median OS than those with hypopharyngeal cancer.

Conclusions: IC significantly improved complete response rates after CRT, and improved outcomes for patients with locally advanced hypopharyngeal, not laryngeal, cancers.
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http://dx.doi.org/10.1002/hed.26353DOI Listing
November 2020

The effect of radiotherapy on taste sensation in head and neck cancer patients - a prospective study.

Radiat Oncol 2020 Jun 5;15(1):144. Epub 2020 Jun 5.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: One of the main side effects of head and neck (H&N) radiation therapy (RT) is alteration in taste sensation. It causes significant morbidity and has a major effect on quality of life (QoL). The aim of this study was to prospectively define the effect of RT on taste sensation (general, and four basic tastes) and correlate these findings with changes in saliva secretion and QoL questionnaires.

Methods: Patients with H&N cancer treated with RT, in which the oral cavity was expected to receive a mean dose of 30 Gray (Gy). Patients were evaluated by Whole-Saliva Sialometry, validated Taste Strips and European Organization for Research and Treatment of Cancer H&N QoL questionnaires prior to RT (T0), mid-point of radiotherapy dose (T1), at the end of radiotherapy (T2) and 1 (T3), 3 (T4) and 12 months (T5) after completion of treatment course.

Results: Twenty-eight patients were recruited, and 21 patients completed study procedures and were analyzed. Median age was 66 years (range 18-90). The most common tumor site was the oral cavity. The median prescribed radiation dose to the high dose volume was 66 (range 60-70). The median mean and max dose to the oral cavity were 25.1 (range 14-69) and 64.9 (range 30-70), respectively. There was a significant decrease in overall taste sensation between T0 and T1 and T2. With specific tastes, there were significant decreases in sensation of sweet and salty, a trend with bitter and no change with sour. All returned to baseline at T3 and onwards. There was no significant correlation between the max or mean dose to the oral cavity and overall taste sensation or between doses to different areas of the tongue and overall or specific tastes. At T0 there was a significant positive correlation between overall taste sensation and whole-saliva sialometry, and at T1 and T2 there were strong trends. There were significant declines in QoL scores during RT.

Conclusions: We found a significant immediate reduction in taste sensation due to RT in H&N cancer patients with taste recovery 1 month after treatment completion. There were strong trends to a correlation with saliva production that requires further exploration.
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http://dx.doi.org/10.1186/s13014-020-01578-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275377PMC
June 2020

Identification of Tumor Antigens in the HLA Peptidome of Patient-derived Xenograft Tumors in Mouse.

Mol Cell Proteomics 2020 08 25;19(8):1360-1374. Epub 2020 May 25.

Department of Biology, Technion-Israel Institute of Technology Haifa, Israel. Electronic address:

Personalized cancer immunotherapy targeting patient-specific cancer/testis antigens (CTA) and neoantigens may benefit from large-scale tumor human leukocyte antigen (HLA) peptidome (immunopeptidome) analysis, which aims to accurately identify antigens presented by tumor cells. Although significant efforts have been invested in analyzing the HLA peptidomes of fresh tumors, it is often impossible to obtain sufficient volumes of tumor tissues for comprehensive HLA peptidome characterization. This work attempted to overcome some of these obstacles by using patient-derived xenograft tumors (PDX) in mice as the tissue sources for HLA peptidome analysis. PDX tumors provide a proxy for the expansion of the patient tumor by re-grafting them through several passages to immune-compromised mice. The HLA peptidomes of human biopsies were compared with those derived from PDX tumors. Larger HLA peptidomes were obtained from the significantly larger PDX tumors as compared with the patient biopsies. The HLA peptidomes of different PDX tumors derived from the same source tumor biopsy were very reproducible, even following subsequent passages to new naïve mice. Many CTA-derived HLA peptides were discovered, as well as several potential neoantigens/variant sequences. Taken together, the use of PDX tumors for HLA peptidome analysis serves as a highly expandable and stable source of reproducible and authentic peptidomes, opening up new opportunities for defining large HLA peptidomes when only small tumor biopsies are available. This approach provides a large source for tumor antigens identification, potentially useful for personalized immunotherapy.
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http://dx.doi.org/10.1074/mcp.RA119.001876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015002PMC
August 2020

CPAP (Continuous Positive Airway Pressure) is an effective and stable solution for heart sparing radiotherapy of left sided breast cancer.

Radiat Oncol 2020 Mar 6;15(1):59. Epub 2020 Mar 6.

Department of Radiotherapy, Davidoff Center Rabin Medical Center and Sackler Faculty of Medicine Tel Aviv University, 49 Jabotinksi St, 49100, Petach Tikvah, Israel.

Purpose: Limiting the heart dose in left sided breast cancer radiotherapy is critical. We sought to study the effect of using CPAP (continuous positive airway pressure) as an aid in reducing heart dose in breast cancer radiotherapy.

Methods: Patients with left sided breast cancer receiving adjuvant radiotherapy were enrolled on a prospective IRB (institutional review board) approved clinical trial utilizing CPAP during radiotherapy. Each patient was simulated and planned with and without CPAP and the best dosimetric results determined the patient's treatment. Data on the differences in lung and heart volume and position as well as boost cavity position with and without CPAP were analyzed.

Results: Twenty-four women from 10/16 to 10/18 were enrolled. Seven patients were not treated on study; only two of these were due to treatment issues. Median age was 54 years. 70% had breast only radiation and 30% were treated to breast\CW (chest wall) and regional nodes. The median lung volume with CPAP was 60% larger than without CPAP. (1637 vs. 996 cc) p < 0.001. The median heart volume decreased 12% with CPAP. (338 vs. 382 cc) In regards to the DVH, CPAP decreased mean heart dose from 3.02 to 1.6Gy (p = .0075) and V20 of the lungs from 17.1 to 13.8 with CPAP but this was not significant.

Conclusion: CPAP assisted radiotherapy was tolerable and produced superior treatment plans in left sided breast cancer. This method is worthy of further investigation as a method to normal tissue sparing treatment of left sided breast cancer patients.
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http://dx.doi.org/10.1186/s13014-020-01505-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060550PMC
March 2020

What is the Best Way to Plan Rectum Three-Dimensional Conformal Radiotherapy in Prone Position-Classic Anatomical Landmark, Three Dimensional Fitting the Planning Target Volume, or Volumetric Modulated Arc?

J Med Imaging Radiat Sci 2020 03 15;51(1):103-107. Epub 2020 Feb 15.

Davidoff Cancer Center, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: Traditionally, rectal cancer radiation therapy uses bony landmark fields to cover common lymphatic drainage sites, including the internal iliac, presacral, and perirectal lymph nodes. We aimed to investigate if bony landmark borders sufficiently cover the internal iliac nodes and to compare tumor volume and normal tissue avoidance using classic bony landmarks (c3DCRT), contoured elective clinical target volume (f3DCRT), and volumetric modulated arc therapy (VMAT) planning in locally advanced rectal cancer.

Methods: Computed tomography datasets of 11 patients with locally advanced rectal cancer who had completed treatment in the prone position on a bellyboard in c3DCRT technique. The elective clinical target volumes and organs at risk were contoured, and a f3DCRT VMAT plan generated for all patients. Planning target volume, gross tumor volume, and normal tissue dose limits were evaluated.

Results: The mean planning target volume 95% coverages were significantly lower for c3DCRT plans, and the lymph node coverage was better for f3DCRT. No differences were found in PTV coverages between f3DCRT and volumetric modulated arc therapy plans. No significant differences among all techniques were found for organs-at-risk constraints. The bladder dosage was higher in the VMAT plan. The c3DCRT technique missed coverage of the internal iliac lymph nodes and exposed smaller bowel, compared with the other methods.

Discussion And Conclusion: Tumor volume coverage was improved by f3DCRT planning, without significant differences in doses to critical structures compared with c3DCRT and was noninferior to VMAT planning. It is recommended that f3DCRT be used in routine clinical practice in radiotherapy treatments for locally advanced rectal cancer.
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http://dx.doi.org/10.1016/j.jmir.2019.12.002DOI Listing
March 2020

Genomic analysis of metastatic rhabdomyosarcoma masquerading as acute leukemia.

Pathol Res Pract 2020 Jan 2;216(1):152779. Epub 2019 Dec 2.

Institute of Hematology, Davidoff Center, Beilinson Hospital, Rabin Medical Center, Petah Tikva, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:

Blast appearing cells in the peripheral blood and bone marrow may occasionally arise from non-hematopoietic tissues. We present a 58 year old female who presented at our emergency room with symptomatic pancytopenia. Several months earlier she was diagnosed and treated for rhabdomyosracoma of the nasopharynx and entered remission. When we examined the bone-marrow aspirate we estimated the number of blasts at 25 %. Based on this evaluation, a provisional diagnosis of acute leukemia was made. However, immunohistochemistry and flow cytometry analysis revealed that the cells presumed to be blasts were in fact rhabdomyosarcoma cells masquerading as leukemia. The mutational landscapes of the primary tumor and the bone marrow metastasis had similar yet distinct profiles. Annotation analysis suggested that the primary and metastatic tumors use alternate mutations to activate the RAS/AKT signaling pathways. In this case, looking beyond the mutational profiling revealed an additional layer of similarity between both the original and metastatic samples, exposing a common and possibly targetable pathway. Application of annotation tools in clinical practice could enable extraction of valuable information from somatic mutational gene panels.
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http://dx.doi.org/10.1016/j.prp.2019.152779DOI Listing
January 2020

Next-generation sequencing in salivary gland carcinoma: Targetable alterations lead to a therapeutic advantage-Multicenter experience.

Head Neck 2020 04 24;42(4):599-607. Epub 2019 Nov 24.

Institute of Oncology, Davidoff Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva, Israel.

Background: Salivary gland cancers (SGCs) are rare. The approach to metastatic patients is histology-dependent. There is little evidence on whether next-generation sequencing (NGS) findings translate to tumor control in SGCs.

Methods: We analyzed all patients with histologically confirmed SGC who underwent NGS.

Results: Twenty-seven patients were identified, 14 (51.8%) had targetable findings in NGS: 5 ERBB2 amplifications, 3 PIK3CA mutations, 2 RUNX1 mutations, 1 TRIM33-RET fusion, 1 FGFR3-TACC3 fusion, 1 microsatellite instability-high, and 2 high mutational burden. Ten patients were treated accordingly. Median progression-free survival for targeted treatment was 8.4 months. Of five patients who achieved durable responses of 8.4 to 31.3 months, two are ongoing. The overall median survival was not reached for patients receiving targeted treatment and was 40.4 months for patients treated conventionally (P = .18).

Conclusions: In the absence of a well-established therapeutic approach, NGS may detect clinically significant genetic alterations and benefit patients with advanced SGC.
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http://dx.doi.org/10.1002/hed.26026DOI Listing
April 2020

Clinical evidence of abscopal effect in cutaneous squamous cell carcinoma treated with diffusing alpha emitters radiation therapy: a case report.

J Contemp Brachytherapy 2019 Oct 30;11(5):449-457. Epub 2019 Oct 30.

Skin Cancer Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola (FC), Italy.

Purpose: Alpha particle treatments could enhance the probability of an immune response, which can lead to abscopal effects (AE). We report a case of a patient affected by multiple cutaneous squamous cell carcinoma (cSCC). After the treatment with diffusing alpha emitters radiation therapy (DaRT) of one lesion, an AE was observed on at least two distant ones.

Material And Methods: We investigated a case of a 65-year-old female patient with multiple synchronous lesions of the skin of lower limbs confirmed by a biopsy. Patient was enrolled in a clinical trial N.CTP-SCC-00 (NCT03015883), with the objective to assess effectiveness of DaRT technique. DaRT is based on the insertion of locally Ra-loaded seeds in a clinical target volume (CTV). Treatment plan with positron emission tomography/computed tomography (PET/CT) was used to entirely cover the CTV. Follow-up and biopsy evaluations were employed to outline the patient outcome.

Results: We performed seeds implantation according to the Paris system. At 28 day, an evident lesion shrinkage with a persistent minimal area of hyperkeratosis was noted. 76 days after implantation, a complete remission of the treated lesion was observed and an evident reduction of the area with two more distant lesion, which could be associated to an immune-mediated response. One year after the treatment, a complete remission of treated lesion was observed as well as spontaneous regression of untreated distant ones.

Conclusions: In this study, we reported evidences of an AE in cSCC stimulated by radiation and possibly mediated by immune system. In the next DaRT treatments, our intent is to monitor T-lymphocytes variations in peripheral blood in order to demonstrate indirect activation of the immune system mediated by radiation also in patients with solitary lesions, in which, by definition, an AE cannot be observed.
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http://dx.doi.org/10.5114/jcb.2019.88138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854861PMC
October 2019

Usefulness of ultrasound and fine needle aspiration cytology of major salivary gland lesions.

Am J Otolaryngol 2020 Jan - Feb;41(1):102293. Epub 2019 Sep 10.

Department of Otolaryngology-Head and Neck Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv 6423906, Israel.

Purpose: To assess the clinical value of ultrasound (US) and fine needle aspiration (FNA) of salivary gland lesions prior to surgery, for preoperative decision-making and long-term follow-up/outcome.

Materials & Methods: We retrospectively analyzed the medical charts of 98 consecutive patients with major salivary gland lesions who were treated in a single medical from 2008 to 2017. Preoperative US and FNA was performed in all patients. Cytology results were compared with histopathological diagnoses. The correlation between preoperative US findings, cytology and histopathological diagnoses was assessed.

Results: Twenty-three specimens were histopathologically malignant, and 75 were diagnosed as benign. Three false-positive results diagnosed as malignant in cytology had a final histology of sialadenitis, pleomorphic adenoma and Warthin's tumor, respectively. In six cases, cytology yielded false-negative results. The overall accuracy of FNA in distinguishing benign from malignant lesions was 91%. Sensitivity was 70% and specificity 93%. There was no significant correlation between US features and final pathology, but larger size had some correlation with malignancy (p = 0.306). No complications were observed during or after performing FNA.

Conclusion: FNA from salivary gland lesions is safe and in many cases can help in preoperative decision making or surgical planning. Hence, the results of FNA cytology should have an integral role in clinical decision-making and management of major salivary gland lesions. False-negative results do occur and therefore should be used only as an adjunctive measure.
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http://dx.doi.org/10.1016/j.amjoto.2019.102293DOI Listing
April 2020

Prognostic factors for survival and nonfunctional larynx in patients with squamous cell carcinoma of the larynx.

Laryngoscope 2020 05 1;130(5):1202-1205. Epub 2019 Jul 1.

Davidoff Cancer Center, Rabin Medical Center, Petach Tikva, Israel.

Objectives/hypothesis: Prognostic variables upon presentation can assist in recommending the optimal treatment for patients and may help in management of patient's expectations and side effects. Our objective was to evaluate prognostic factors for survival and nonfunctional larynx in patients with laryngeal squamous cell carcinoma (SCC).

Study Design: Retrospective chart review.

Methods: All patients diagnosed as having laryngeal SCC from January 2007 through December 2016 in a tertiary, university-affiliated medical center were reviewed. Main outcomes were survival and nonfunctional larynx rate.

Results: Two hundred sixty-five patients were identified; the male:female ratio was 4.5:1. Mean age at diagnosis was 64 ± 11.8 years. Overall and disease-free survival were 7.9 and 6.7 years, respectively. A univariate analysis found that older age significantly affected survival. Alcohol abuse, diabetes mellitus, and advanced disease stage at presentation were also found to decrease survival but were not significant. A multivariate Cox regression found age, alcohol abuse, and advanced disease stage to significantly affect and lower survival (P < .05). Of the entire cohort 19% were defined as having a nonfunctional larynx (e.g., tracheostomy or feeding-tube dependent). A backward logistic regression found that male sex and advanced disease stage increased the risk, and anterior commissure involvement was found to lower the probability of nonfunctional larynx (P < .01).

Conclusions: Older age, history of alcohol use, and advanced disease stage at presentation negatively affect survival in larynx cancer patients. Male gender and advanced disease stage increased the risk, and anterior commissure involvement was found to lower the risk for tracheostomy or feeding-tube dependency.

Level Of Evidence: 4 Laryngoscope, 130:1202-1205, 2020.
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http://dx.doi.org/10.1002/lary.28173DOI Listing
May 2020

MET activation confers resistance to cetuximab, and prevents HER2 and HER3 upregulation in head and neck cancer.

Int J Cancer 2019 08 11;145(3):748-762. Epub 2019 Feb 11.

The Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

An understanding of the mechanisms underlying acquired resistance to cetuximab is urgently needed to improve cetuximab efficacy in patients with head and neck squamous cell carcinoma (HNSCC). Here, we present a clinical observation that MET pathway activation constitutes the mechanism of acquired resistance to cetuximab in a patient with HNSCC. Specifically, RNA sequencing and mass spectrometry analysis of cetuximab-sensitive (Cetux ) and cetuximab-resistant (Cetux ) tumors indicated MET amplification and overexpression in the Cetux tumor compared to the Cetux lesion. Stimulation of MET in HNSCC cell lines was sufficient to reactivate the MAPK pathway and to confer resistance to cetuximab in vitro and in vivo. In addition to the direct role of MET in reactivation of the MAPK pathway, MET stimulation abrogates the well-known cetuximab-induced compensatory feedback loop of HER2/HER3 expression. Mechanistically, we showed that the overexpression of HER2 and HER3 following cetuximab treatment is mediated by the ETS homologous transcription factor (EHF), and is suppressed by MET/MAPK pathway activation. Collectively, our findings indicate that evaluation of MET and HER2/HER3 in response to cetuximab in HNSCC patients can provide the rationale of successive line of treatment.
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http://dx.doi.org/10.1002/ijc.32170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6554031PMC
August 2019

Safety and efficacy of two starting doses of vandetanib in advanced medullary thyroid cancer.

Endocr Relat Cancer 2019 02;26(2):241-250

Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.

Vandetanib is an oral tyrosine kinase inhibitor approved for treatment of advanced symptomatic or progressive medullary thyroid cancer (MTC). The current study (Nbib1496313) evaluated the benefit-risk of two starting doses of vandetanib in patients with symptomatic or progressive MTC. Patients were randomized 1:1 to receive vandetanib 150 or 300 mg daily and followed for a maximum of 14 months (Part A), with the option to then enter an open-label phase (Part B) investigating vandetanib 100, 150, 200 and 300 mg daily doses. Efficacy was assessed in Part A, and safety and tolerability during Parts A and B up to 2 years post randomization. Eighty-one patients were randomized in Part A and 61 patients entered Part B, of whom 37 (60.7%) received 2 years of treatment. Overall, 25% of patients experienced an objective response (OR) at 14 months (OR rate, 0.29 (95% CI, 0.176-0.445) for 300 mg, and 0.20 (95% CI, 0.105-0.348) for 150 mg; one-sided P value approximately 0.43). The most common adverse events (AEs) included diarrhea, hypocalcemia, asthenia, QTc prolongation, hypokalemia and keratopathy, all at generally higher incidence with 300 vs 150 mg (Part A). Part B safety and tolerability was consistent with Part A. OR was observed with both vandetanib doses; the 300 mg dose showed a more favorable trend vs 150 mg as initial dose. Thus, for most patients, 300 mg vandetanib is the most appropriate starting dose; dose reductions to manage AEs and lower initial doses for patients with particular comorbidities can be considered.
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http://dx.doi.org/10.1530/ERC-18-0258DOI Listing
February 2019

Nonmelanoma skin cancer of the head and neck region in solid organ transplant recipients.

Head Neck 2019 02 14;41(2):374-380. Epub 2018 Dec 14.

Department of Otolaryngology, Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.

Background: Nonmelanoma skin cancers (NMSC) are the most common malignancies in solid organ recipients. We investigated the incidence, clinical features, and outcome of solid organ recipients with NMSC of the head and neck.

Methods: A retrospective chart review was conducted for solid organ recipients who were treated from 1992 to 2015 and who developed NMSC of the head and neck.

Results: Of 3339 organ recipients, 259 patients developed 697 head and neck NMSC. Squamous cell carcinoma was the most common malignancy (55%). The overall 5-year and 10-year survival was 68% and 45%. Kidney recipients had better survival outcome than other organ recipients (10 vs 7 years). Advanced-stage cancers (10%), aggressive patterns of tumors (21%), and treatment with Prograf and Cellcept were associated with increased disease-specific mortality.

Conclusion: Solid organ transplant increases the risk of NMSC of the head and neck. Aggressive tumors decrease patient survival and warrant more decisive and multidisciplinary approach.
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http://dx.doi.org/10.1002/hed.25467DOI Listing
February 2019

Optimisation of treatment with lenvatinib in radioactive iodine-refractory differentiated thyroid cancer.

Cancer Treat Rev 2018 Sep 2;69:164-176. Epub 2018 Jul 2.

Medical Oncology Department, MD Anderson Cancer Center Madrid, Spain.

Lenvatinib has been approved for the treatment of advanced differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) following the results of the SELECT trial which demonstrated a significant increase in progression-free survival and a high response rates. The data reported for lenvatinib in RAI-refractory DTC (RAI-R DTC) are the most significant to date in this patient population, with a RECIST objective response rate above 60% and almost 80% reduction in the risk of disease progression. Because the first indication in oncology for lenvatinib is specifically in RAI-R DTC, a period of familiarisation with its safety and efficacy profile is required. This review includes a series of specific recommendations for optimising the management of RAI-R DTC with lenvatinib, as well as specific guidelines for minimising the incidence and severity of adverse events (AEs), which enable dose intensity to be increased and this way maximise the benefits of the drug in the patient population treated. These recommendations were defined at a meeting of experts of different specialities, reviewing available scientific evidence on the drug, as well as their own direct personal experience in daily clinical practice. For toxicity to be properly managed, a multidisciplinary approach is required in which the different medical services, nursing staff and the patient and their careers are all involved. It is essential to assess the suitability of patients who are candidates for lenvatinib, as well as their clinical and physiological status prior to treatment. They must then be closely monitored to prevent and detect possible AEs. The main objective should be to maintain the dose that obtains the maximum therapeutic effect, discontinuing the treatment only if the toxicity becomes unmanageable or there is no clinical benefit.
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http://dx.doi.org/10.1016/j.ctrv.2018.06.019DOI Listing
September 2018

Cisplatin-conjugated gold nanoparticles as a theranostic agent for head and neck cancer.

Head Neck 2018 Jan 11;40(1):70-78. Epub 2017 Nov 11.

Faculty of Engineering and the Institutes of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel.

Background: The purpose of this study was to develop a nanoplatform, which simultaneously acts as radiosensitizer, drug carrier, and tumor imaging agent for head and neck cancer.

Methods: We synthesized 20 nm gold nanoparticles, coated with glucose and cisplatin (CG-GNPs). Their penetration into tumor cells and their cellular toxicity were evaluated in vitro. In vivo experiments were conducted to evaluate their impact on tumor growth and their imaging capabilities.

Results: The CG-GNPs showed efficient penetration into tumor cells and similar cellular toxicity as cisplatin alone. Combined with radiation, CG-GNPs led to greater tumor reduction than that of radiation alone and radiation with free cisplatin. The CG-GNPs also demonstrated efficient tumor imaging capabilities.

Conclusion: Our CG-GNPs have a great potential to increase antitumor effect, overcome resistance to chemotherapeutics and radiation, and allow imaging-guided therapy.
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http://dx.doi.org/10.1002/hed.24935DOI Listing
January 2018

Can molecular profiling enhance radiotherapy? Impact of personalized targeted gold nanoparticles on radiosensitivity and imaging of adenoid cystic carcinoma.

Theranostics 2017 14;7(16):3962-3971. Epub 2017 Sep 14.

Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, Israel.

Personalized molecular profiling has an established role in selection of treatment for metastatic disease; however, its role in improving radiosensitivity and functional imaging has not been evaluated. In the current study, we examined molecular profiling as a tool for designing personalized targeted gold nanoparticles (GNP) to serve as dual-modal tumor radiosensitizers and functional imaging enhancers. To this end, molecular profiling of a patient's salivary gland adenoid cystic carcinoma (ACC) was performed, and anaplastic lymphoma kinase (ALK) mutation was detected. The extracted tumor was subcutaneously injected into mice, which were then treated either with radiation, the specific ALK inhibitor crizotinib, or a combination of therapies. One of these combinations, namely, ALK-targeted GNP (via crizotinib coating), was found to enhance radiation treatment, as demonstrated by a significant decrease in tumor volume over 24 days. In parallel, ALK-targeted GNP substantially augmented tumor visualization via computed tomography. The mechanism of radiosensitivity enhancement was mostly related to a diminished cell repair mechanism in tumors, as demonstrated by proliferating cell nuclear antigen staining. These findings indicate that personalized molecular profiling is an effective technique for enhancing cancer theranostics.
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http://dx.doi.org/10.7150/thno.19615DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5667418PMC
June 2018

Assessment of laryngeal cancer in patients younger than 40 years.

Laryngoscope 2018 Jul 27;128(7):1602-1605. Epub 2017 Oct 27.

Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petach Tikva, Israel.

Objectives/hypothesis: To assess the differences between patients with laryngeal squamous cell carcinoma under 40 years old and those 40 years old or older. A secondary objective was to compare survival outcome between these cohorts.

Study Design: Retrospective chart review.

Methods: We reviewed the medical charts of all patients treated in our tertiary referral center for laryngeal squamous cell carcinoma from 2005 to 2014. Patients aged < 40 years at diagnosis were compared to older patients.

Results: The study group comprised 160 patients. Of them, 13 were aged < 40 years at diagnosis. Mean age was 35 ± 3.9 years and 64.4 ± 11 years for the two groups. Among the younger patients, 38% were smokers (mean pack/day, 2.2) versus 71% in the older group (mean pack/day, 3). The younger group typically had a more advanced stage than the older group at presentation; eight young patients (62%) had stage III or IV versus 49 (33%) in the older group (P = .042). Mean overall survival was 6.7 ± 1 years for those under 40 years old and 7.7 ± 0.2 years for the older patients (P = .2). The 5-year survival rate was 69% for young patients and 90% for the older group (P = .04). However, there was no significant between-group difference in overall survival or 5-year survival rate when stratified for early- and late-stage disease.

Conclusions: There is a lower prevalence of classic risk factors in younger patient with laryngeal carcinoma in this study, suggesting a different etiology compared to our older cohort. The under-40 cohort presented with more advanced disease and had a worse 5-year survival; however, when stratified for early- versus late-stage disease, there was no significant difference in overall or 5-year survival between the groups. This may suggest that, despite a different etiology, laryngeal cancer behaves similarly in older and younger patients.

Level Of Evidence: 4. Laryngoscope, 128:1602-1605, 2018.
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http://dx.doi.org/10.1002/lary.26951DOI Listing
July 2018

Characteristics and outcome of laryngeal squamous cell carcinoma in young adults.

Oncol Lett 2017 Mar 21;13(3):1393-1397. Epub 2016 Dec 21.

Department of Clinical Otolaryngology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 6997801, Israel.

Laryngeal carcinoma rarely occurs in the young adult population. Therefore, the optimal treatment for this age group is unclear, specifically regarding organ preservation treatment. In order to assess the distinct characteristics of laryngeal squamous cell carcinoma (SCC) in young adults and describe the effect of treatment on survival, a retrospective chart review of all patients aged <40 years, who were treated in a tertiary referral center for laryngeal SCC between January 1960 and December 2013, was performed. Patients who were treated prior to and following the Veterans study, representing an arbitrary point which started the organ preservation era, were compared. A total of 29 patients (male:female ratio, 2.6:1) were identified. The mean age at diagnosis was 35±5 years and 17 patients (59%) were smokers. In total, 12 (41%) of patients were stage I, 4 (14%) were stage II, 8 (28%) were stage III and 5 (17%) were stage IV. Glottic tumors were present in 20 (69%) of patients and supraglottic tumors in 6 (21%); the site of tumor origin could not be determined in 3 (10%) of patients. Surgery was performed in 11 (38%) of patients, radiation in 21 (72%) and chemotherapy in 5 (17%). A comparison between patients treated prior to and following the Veterans study demonstrated a 2-year higher laryngectomy-free survival rate of 53% and 78%, respectively (P=0.299). The 2-year disease-free survival rate was 93% for patients who were treated prior to the Veterans study and 71% for patients who were treated after (P=0.001), with no significant change in overall survival (P=0.413). The results suggest that the characteristics and behavior of laryngeal carcinoma in young adults is similar to older adults. Higher rates of 2-year laryngectomy-free survival were noted in patients treated following the organ preservation era with no significant difference in survival compared with patients who were treated before.
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http://dx.doi.org/10.3892/ol.2016.5528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5403180PMC
March 2017

Role of Induction Chemotherapy Prior to Chemoradiation in Head and Neck Squamous Cell Cancer-Systematic Review and Meta-analysis.

Cancer J 2017 Mar/Apr;23(2):79-83

From the *Davidoff Cancer Center, Rabin Medical Center-Beilinson Hospital, Petah Tikva; †Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; and ‡Division of Hematology/Oncology, Department of Medicine, and Translational Science, UC San Diego Moores Cancer Center, La Jolla, CA.

The objective of this study was to review and assess the impact of additional induction chemotherapy to concomitant chemoradiation in head and neck squamous cell cancer. We performed a comparative systematic review and meta-analysis of clinical trials of induction chemotherapy + chemoradiation and chemoradiation alone in this setting. We identified trials randomizing 1314 patients (published 2004-2015). A non-statistically significant trend was observed in favor of induction chemotherapy + chemoradiation on overall survival (hazard ratio, 0.88; 95% confidence interval, 0.75-1.04). Disease control was superior in the induction chemotherapy + chemoradiation group (hazard ratio, 0.69; 95% confidence interval, 0.57-0.83). The rate of complete response improved with induction chemotherapy compared with concomitant chemoradiation (relative risk, 1.52; 95% confidence interval, 1.20-1.92). This study showed no benefit of induction chemotherapy + chemoradiation on overall survival. However, improved complete response rate and death certificate-only registrations may imply that selected patients may benefit from induction chemotherapy.
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http://dx.doi.org/10.1097/PPO.0000000000000253DOI Listing
May 2017

T1 squamous cell carcinoma of the glottis with anterior commissure involvement: Radiotherapy versus transoral laser microsurgery.

Head Neck 2017 06 28;39(6):1101-1105. Epub 2017 Mar 28.

Department of Radiation Oncology, Davidoff Cancer Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Background: The optimal treatment method of T1 glottic squamous cell carcinoma (SCC) with involvement of the anterior commissure is still debatable. We compared the outcomes of radiotherapy (RT) and transoral laser microsurgery (TLM).

Methods: Data were retrospectively collected for 54 patients who were treated by RT (n = 38) or TLM (n = 16) from 2006 to 2013.

Results: No between-group differences were found in demographic or risk factors. Recurrence was noted in 6 patients of the TLM group and 5 of the RT group. There was a near-significant association of TLM with recurrence (p = .053). Radiation was associated with a higher 5-year disease-free survival (DFS) (87.3% vs 74.9%; p = .037). Both groups had excellent rates for local control (75% and 97%, respectively), and overall survival (78.9 and 87.5%, respectively). There were no significant differences in outcome parameters by tumor classification.

Conclusion: TLM is associated with higher recurrence rates and lower DFS. Both patients with T1a and T1b disease had the same outcome parameters. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1101-1105, 2017.
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http://dx.doi.org/10.1002/hed.24723DOI Listing
June 2017