Publications by authors named "Baris Karakullukcu"

45 Publications

Neoadjuvant immunotherapy with nivolumab and ipilimumab induces major pathological responses in patients with head and neck squamous cell carcinoma.

Nat Commun 2021 12 22;12(1):7348. Epub 2021 Dec 22.

Division of Molecular Oncology & Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Surgery for locoregionally advanced head and neck squamous cell carcinoma (HNSCC) results in 30‒50% five-year overall survival. In IMCISION (NCT03003637), a non-randomized phase Ib/IIa trial, 32 HNSCC patients are treated with 2 doses (in weeks 1 and 3) of immune checkpoint blockade (ICB) using nivolumab (NIVO MONO, n = 6, phase Ib arm A) or nivolumab plus a single dose of ipilimumab (COMBO, n = 26, 6 in phase Ib arm B, and 20 in phase IIa) prior to surgery. Primary endpoints are feasibility to resect no later than week 6 (phase Ib) and primary tumor pathological response (phase IIa). Surgery is not delayed or suspended for any patient in phase Ib, meeting the primary endpoint. Grade 3‒4 immune-related adverse events are seen in 2 of 6 (33%) NIVO MONO and 10 of 26 (38%) total COMBO patients. Pathological response, defined as the %-change in primary tumor viable tumor cell percentage from baseline biopsy to on-treatment resection, is evaluable in 17/20 phase IIa patients and 29/32 total trial patients (6/6 NIVO MONO, 23/26 COMBO). We observe a major pathological response (MPR, 90‒100% response) in 35% of patients after COMBO ICB, both in phase IIa (6/17) and in the whole trial (8/23), meeting the phase IIa primary endpoint threshold of 10%. NIVO MONO's MPR rate is 17% (1/6). None of the MPR patients develop recurrent HSNCC during 24.0 months median postsurgical follow-up. FDG-PET-based total lesion glycolysis identifies MPR patients prior to surgery. A baseline AID/APOBEC-associated mutational profile and an on-treatment decrease in hypoxia RNA signature are observed in MPR patients. Our data indicate that neoadjuvant COMBO ICB is feasible and encouragingly efficacious in HNSCC.
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http://dx.doi.org/10.1038/s41467-021-26472-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8695578PMC
December 2021

Translation of c-Met Targeted Image-Guided Surgery Solutions in Oral Cavity Cancer-Initial Proof of Concept Data.

Cancers (Basel) 2021 May 28;13(11). Epub 2021 May 28.

Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands.

Intraoperative tumor identification (extension/margins/metastases) via receptor-specific targeting is one of the ultimate promises of fluorescence-guided surgery. The translation of fluorescent tracers that enable tumor visualization forms a critical component in the realization of this approach. Ex vivo assessment of surgical specimens after topical tracer application could help provide an intermediate step between preclinical evaluation and first-in-human trials. Here, the suitability of the c-Met receptor as a potential surgical target in oral cavity cancer was explored via topical ex vivo application of the fluorescent tracer EMI-137. Freshly excised tumor specimens obtained from ten patients with squamous cell carcinoma of the tongue were incubated with EMI-137 and imaged with a clinical-grade Cy5 prototype fluorescence camera. In-house developed image processing software allowed video-rate assessment of the tumor-to-background ratio (TBR). Fluorescence imaging results were related to standard pathological evaluation and c-MET immunohistochemistry. After incubation with EMI-137, 9/10 tumors were fluorescently illuminated. Immunohistochemistry revealed c-Met expression in all ten specimens. Non-visualization could be linked to a more deeply situated lesion. Tumor assessment was improved via video representation of the TBR (median TBR: 2.5 (range 1.8-3.1)). Ex vivo evaluation of tumor specimens suggests that c-Met is a possible candidate for fluorescence-guided surgery in oral cavity cancer.
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http://dx.doi.org/10.3390/cancers13112674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198422PMC
May 2021

c-MET Receptor-Targeted Fluorescence on the Road to Image-Guided Surgery in Penile Squamous Cell Carcinoma Patients.

J Nucl Med 2022 01 14;63(1):51-56. Epub 2021 May 14.

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands;

In penile squamous cell carcinoma (pSCC), primary surgery aims to obtain oncologically safe margins while minimizing mutilation. Surgical guidance provided by receptor-specific tracers could potentially improve margin detection and reduce unnecessary excision of healthy tissue. Here, we present the first results of a prospective feasibility study for real-time intraoperative visualization of pSCC using a fluorescent mesenchymal-epithelial transition factor (c-MET) receptor targeting tracer (EMI-137). EMI-137 tracer performance was initially assessed ex vivo ( = 10) via incubation of freshly excised pSCC in a solution containing EMI-137 (500 nM). The in vivo potential of c-MET targeting and intraoperative tumor visualization was assessed after intravenous administration of EMI-137 to 5 pSCC patients scheduled for surgical resection using a cyanine-5 fluorescence camera. Fluorescence imaging results were related to standard pathologic tumor evaluation and c-MET immunohistochemistry. Three of the 5 in vivo patients also underwent a sentinel node resection after local administration of the hybrid tracer indocyanine green- Tc-nanocolloid, which could be imaged using a near-infrared fluorescence camera. No tracer-related adverse events were encountered. Both ex vivo and in vivo, EMI-137 enabled c-MET-based tumor visualization in all patients. Histopathologic analyses showed that all pSCCs expressed c-MET, with expression levels of at least 70% in 14 of 15 patients. Moreover, the highest c-MET expression levels were seen on the outside rim of the tumors, and a visual correlation was found between c-MET expression and fluorescence signal intensity. No complications were encountered when combining primary tumor targeting with lymphatic mapping. As such, simultaneous use of cyanine-5 and indocyanine green in the same patient proved to be feasible. Fluorescence imaging of c-MET receptor- expressing pSCC tumors after intravenous injection of EMI-137 was shown to be feasible and can be combined with fluorescence-based lymphatic mapping. This combination is unique and paves the way toward further development of this surgical guidance approach.
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http://dx.doi.org/10.2967/jnumed.120.261864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8717176PMC
January 2022

Technologic (R)Evolution Leads to Detection of More Sentinel Nodes in Patients with Melanoma in the Head and Neck Region.

J Nucl Med 2021 10 26;62(10):1357-1362. Epub 2021 Feb 26.

Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

Sentinel lymph node (SN) biopsy (SNB) has proven to be a valuable tool for staging melanoma patients. Since its introduction in the early 1990s, this procedure has undergone several technologic refinements, including the introduction of SPECT/CT, as well as radioguidance and fluorescence guidance. The purpose of the current study was to evaluate the effect of this technologic evolution on SNB in the head and neck region. The primary endpoint was the false-negative (FN) rate. Secondary endpoints were number of harvested SNs, overall operation time, operation time per harvested SN, and postoperative complications. A retrospective database was queried for cutaneous head and neck melanoma patients who underwent SNB at The Netherlands Cancer Institute between 1993 and 2016. The implementation of new detection techniques was divided into 4 groups: 1993-2005, with preoperative lymphoscintigraphy and intraoperative use of both a γ-ray detection probe and patent blue ( = 30); 2006-2007, with addition of preoperative road maps based on SPECT/CT ( = 15); 2008-2009, with intraoperative use of a portable γ-camera ( = 40); and 2010-2016, with addition of near-infrared fluorescence guidance ( = 192). In total, 277 patients were included. At least 1 SN was identified in all patients. A tumor-positive SN was found in 59 patients (21.3%): 10 in group 1 (33.3%), 3 in group 2 (20.0%), 6 in group 3 (15.0%), and 40 in group 4 (20.8%). Regional recurrences in patients with tumor-negative SNs resulted in an overall FN rate of 11.9% (group 1, 16.7%; group 2, 0%; group 3, 14.3%; group 4, 11.1%). The number of harvested nodes increased with advancing technologies ( = 0.003), whereas Breslow thickness and operation time per harvested SN decreased ( = 0.003 and = 0.017, respectively). There was no significant difference in percentage of tumor-positive SNs, overall operation time, and complication rate between the different groups. The use of advanced detection technologies led to a higher number of identified SNs without an increase in overall operation time, possibly indicating an improved surgical efficiency. Operation time per harvested SN decreased; the average FN rate remained 11.9% and was unchanged over 23 y. There was no significant change in postoperative complication rate.
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http://dx.doi.org/10.2967/jnumed.120.246819DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724899PMC
October 2021

Surgical site complications of post-chemoradiotherapy neck dissection: Urgent need for standard registration.

Eur J Surg Oncol 2021 Apr 15;47(4):764-771. Epub 2020 Oct 15.

Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Department of Oral and Maxillofacial Surgery, Amsterdam UMC, Amsterdam, the Netherlands.

Nowadays, a substantial number of head and neck cancer patients are treated by organ-preserving chemoradiation (CRT), with a possible increased risk of complications after planned or salvage neck dissections. We try to determine the risk pattern of surgical site complications (SSC) post-CRT.
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http://dx.doi.org/10.1016/j.ejso.2020.10.015DOI Listing
April 2021

On the Development of a Light Dosimetry Planning Tool for Photodynamic Therapy in Arbitrary Shaped Cavities: Initial Results.

Photochem Photobiol 2020 03 13;96(2):405-416. Epub 2020 Feb 13.

Verwelius 3D lab, Department of Head and Neck Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Previous dosimetric studies during photodynamic therapy (PDT) of superficial lesions within a cavity such as the nasopharynx, demonstrated significant intra- and interpatient variations in fluence rate build-up as a result of tissue surface re-emitted and reflected photons, which depends on the optical properties. This scattering effect affects the response to PDT. Recently, a meta-tetra(hydroxyphenyl)chlorin-mediated PDT study of malignancies in the paranasal sinuses after salvage surgery was initiated. These geometries are complex in shape, with spatially varying optical properties. Therefore, preplanning and in vivo dosimetry is required to ensure an effective fluence delivered to the tumor. For this purpose, two 3D light distribution models were developed: first, a simple empirical model that directly calculates the fluence rate at the cavity surface using a simple linear function that includes the scatter contribution as function of the light source to surface distance. And second, an analytical model based on Lambert's cosine law assuming a global diffuse reflectance constant. The models were evaluated by means of three 3D printed optical phantoms and one porcine tissue phantom. Predictive fluence rate distributions of both models are within ± 20% accurate and have the potential to determine the optimal source location and light source output power settings.
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http://dx.doi.org/10.1111/php.13216DOI Listing
March 2020

Mapping of sentinel lymph node drainage using SPECT/CT to tailor elective nodal irradiation in head and neck cancer patients (SUSPECT-2): a single-center prospective trial.

BMC Cancer 2019 Nov 14;19(1):1110. Epub 2019 Nov 14.

Department of Radiation Oncology, The Netherlands Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands.

Background: The majority of patients with head and neck squamous cell carcinoma (HNSCC) receive bilateral elective nodal irradiation (ENI), in order to reduce the risk of regional failure. Bilateral ENI, as compared to unilateral ENI, is associated with higher incidence of acute and late radiation-induced toxicity with subsequent deterioration of quality of life. Increasing evidence that the incidence of contralateral regional failure (cRF) in lateralized HNSCC is very low (< 10%) suggests that it can be justified to treat selected patients unilaterally. This trial aims to minimize the proportion of patients that undergo bilateral ENI, by using lymph drainage mapping by SPECT/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation.

Methods: In this one-armed, single-center prospective trial, patients with primary T1-4 N0-2b HNSCC of the oral cavity, oropharynx, larynx (except T1 glottic) or hypopharynx, not extending beyond the midline and planned for primary (chemo) radiotherapy, are eligible. After Tc-nanocolloid tracer injection in and around the tumor, lymphatic drainage is visualized using SPECT/CT. In case of contralateral lymph drainage, a contralateral sentinel node procedure is performed on the same day. Patients without contralateral lymph drainage, and patients with contralateral drainage but without pathologic involvement of any removed contralateral sentinel nodes, receive unilateral ENI. Only when tumor cells are found in a contralateral sentinel node the patient will be treated with bilateral ENI. The primary endpoint is cumulative incidence of cRF at 1 and 2 years after treatment. Secondary endpoints are radiation-related toxicity and quality of life. The removed lymph nodes will be studied to determine the prevalence of occult metastatic disease in contralateral sentinel nodes.

Discussion: This single-center prospective trial aims to reduce the incidence and duration of radiation-related toxicities and improve quality of life of HNSCC patients, by using lymph drainage mapping by SPECT/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation.

Trial Registration: ClinicalTrials.gov Identifier: NCT03968679, date of registration: May 30, 2019.
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http://dx.doi.org/10.1186/s12885-019-6331-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857144PMC
November 2019

Surgical site complications after parotid gland surgery for benign tumors in a centralized setting: A Clavien-Dindo class cohort analysis.

Eur J Surg Oncol 2020 02 31;46(2):258-262. Epub 2019 Oct 31.

Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands; Department of Oral and Maxillofacial Surgery, Amsterdam University Medical Center, Amsterdam, the Netherlands.

Background: Surgical resection is the standard of care for parotid gland tumors. Comprehensive reports on the surgical complications of parotidectomy are lacking. This study focuses on surgical wound complications of parotid gland surgery.

Patients And Methods: In the period 2002-2012, 390 consecutive patients (395 procedures) who underwent parotid gland surgery were selected for retrospective analysis. Based on subsequent management, the impact of surgical site complications was graded by the Clavien-Dindo Classification (CDC).

Results: In 83 (21.0%) of the procedures, at least one complication was registered. In total, 118 complications were described. Rated to CDC, 61 patients (15.4%) were graded as class 2 or higher. This implies therapy was dictated. Fortyfive (11.4%) of the complications were surgical site infections (SSI). In 9 patients (2.3%) surgical complications required a surgical intervention under general anesthesia (CDC class 3b), and in 19 patients (4.8%) other invasive treatment (CDC class 3a) was needed.

Conclusions: The Clavien-Dindo Classification proved to be very useful for retrospective registration of surgical complications. Of the 61 patients, 33 were managed by conservative therapy. No risk profile was found for patients at risk for direct surgical complications.
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http://dx.doi.org/10.1016/j.ejso.2019.10.028DOI Listing
February 2020

Toward assessment of resection margins using hyperspectral diffuse reflection imaging (400-1,700 nm) during tongue cancer surgery.

Lasers Surg Med 2020 07 15;52(6):496-502. Epub 2019 Sep 15.

Department of Surgery, Netherlands Cancer Institute, Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

Background And Objectives: There is a clinical need to assess the resection margins of tongue cancer specimens, intraoperatively. In the current ex vivo study, we evaluated the feasibility of hyperspectral diffuse reflectance imaging (HSI) for distinguishing tumor from the healthy tongue tissue.

Study Design/materials And Methods: Fresh surgical specimens (n = 14) of squamous cell carcinoma of the tongue were scanned with two hyperspectral cameras that cover the visible and near-infrared spectrum (400-1,700 nm). Each pixel of the hyperspectral image represents a measure of the diffuse optical reflectance. A neural network was used for tissue-type prediction of the hyperspectral images of the visual and near-infrared data sets separately as well as both data sets combined.

Results: HSI was able to distinguish tumor from muscle with a good accuracy. The diagnostic performance of both wavelength ranges (sensitivity/specificity of visual and near-infrared were 84%/80% and 77%/77%, respectively) appears to be comparable and there is no additional benefit of combining the two wavelength ranges (sensitivity and specificity were 83%/76%).

Conclusions: HSI has a strong potential for intra-operative assessment of tumor resection margins of squamous cell carcinoma of the tongue. This may optimize surgery, as the entire resection surface can be scanned in a single run and the results can be readily available. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/lsm.23161DOI Listing
July 2020

Toward complete oral cavity cancer resection using a handheld diffuse reflectance spectroscopy probe.

J Biomed Opt 2018 10;23(12):1-8

Netherlands Cancer Institute, Antoni van Leeuwenhoek, Department of Surgery, Amsterdam, The Netherlands.

This ex-vivo study evaluates the feasibility of diffuse reflectance spectroscopy (DRS) for discriminating tumor from healthy tissue, with the aim to develop a technology that can assess resection margins for the presence of tumor cells during oral cavity cancer surgery. Diffuse reflectance spectra were acquired on fresh surgical specimens from 28 patients with oral cavity squamous cell carcinoma. The spectra (400 to 1600 nm) were detected after illuminating tissue with a source fiber at 0.3-, 0.7-, 1.0-, and 2.0-mm distances from a detection fiber, obtaining spectral information from different sampling depths. The spectra were correlated with histopathology. A total of 76 spectra were obtained from tumor tissue and 110 spectra from healthy muscle tissue. The first- and second-order derivatives of the spectra were calculated and a classification algorithm was developed using fivefold cross validation with a linear support vector machine. The best results were obtained by the reflectance measured with a 1-mm source-detector distance (sensitivity, specificity, and accuracy are 89%, 82%, and 86%, respectively). DRS can accurately discriminate tumor from healthy tissue in an ex-vivo setting using a 1-mm source-detector distance. Accurate validation methods are warranted for larger sampling depths to allow for guidance during oral cavity cancer excision.
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http://dx.doi.org/10.1117/1.JBO.23.12.121611DOI Listing
October 2018

Feasibility of Salvage Selective Neck Dissection after Primary Irradiation of Pharyngeal and Laryngeal Carcinoma.

ORL J Otorhinolaryngol Relat Spec 2018 9;80(1):10-18. Epub 2018 Feb 9.

Department of Head and Neck Surgical Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, the Netherlands.

Introduction: The concept of neck dissection (ND) in the management armamentarium of head and neck squamous cell carcinoma has evolved throughout the years. Nowadays, ND becomes more functional.

Methodology: A retrospective study of 865 patients was performed at Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital to investigate the feasibility of selective ND (SND). All patients with squamous cell carcinoma of the pharynx and larynx who received primary radiation and underwent salvage ND were included in the study.

Result: A total of 29 NDs were analyzed. In 17 neck sides, viable metastases were found (58%), whereas in the other 12 specimens there were no viable metastases. In 16 of the 17 necks (94%), the metastases were located either in level II, III, or IV or in a combination of these 3 levels. Level V was involved in only 1 case (6%).

Conclusion: It is well justified to perform a salvage SND (levels II, III, and IV) for pharyngeal and laryngeal carcinoma after primary radiation. In carefully selected cases of supraglottic and oropharyngeal carcinoma, a superselective ND also appears as an efficient option.
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http://dx.doi.org/10.1159/000486371DOI Listing
November 2018

A Review of Photodynamic Therapy for Neoplasms of the Head and Neck.

Adv Ther 2018 03 7;35(3):324-340. Epub 2018 Feb 7.

International Head and Neck Scientific Group, Padua, Italy.

Photodynamic therapy (PDT) involves the use of a phototoxic drug which is activated by low powered laser light to destroy neoplastic cells. Multiple photosensitizers have been studied and tumors have been treated in a variety of head and neck sites over the last 30 years. PDT can effectively treat head and neck tumors, particularly those of the superficial spreading type, and the classic application of this technology has been in the patient with a wide field of dysplastic change and superficial carcinomatosis. Interstitial treatment has been used to treat more invasive cancer. Data is available from case series and institutional experiences, but very little randomized data is available. We review the mechanisms of action, historical development, available data, and current knowledge regarding PDT for the various head and neck subsites, and discuss possible future directions, with an emphasis on clinical application.
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http://dx.doi.org/10.1007/s12325-018-0659-3DOI Listing
March 2018

Definitive (chemo)radiotherapy is a curative alternative for standard of care in advanced stage squamous cell carcinoma of the oral cavity.

Oral Oncol 2017 12;75:163-168

Department of Head and Neck Surgery, Netherlands Cancer Institute - Antoni van Leeuwenhoek (NKI-AVL), Amsterdam, The Netherlands; Department of Oral and Maxillofacial Surgery, Academic Medical Center, University of Amsterdam, The Netherlands.

Objective: To compare outcome after definitive (chemo)radiotherapy (CRT group) with standard of care (surgery group) for advanced stage oral cavity carcinoma (OCC). Although definitive (chemo)radiotherapy is assumed to be inferior to surgery with regard to disease control, data on outcome of this approach are scarce.

Methods: Retrospective analysis by chart review (2000-2013). Endpoints were locoregional control (LRC), disease-free survival (DFS), disease specific survival (DSS) and overall survival (OS).

Results: Between the CRT-group (n = 100) and Surgery-group (n = 109), baseline characteristics were equally distributed except stage and local tumor diameter (all p ≤ .001). In the CRT group, at 5 years the LRC rate was 49%, DFS 22%, DSS 39% and OS 22%. In the surgery group, at 5 years the LRC rate was 77%, DFS 45%, DSS 64% and OS 45%. The survival curves of the two groups significantly differed for LRC (p < .001), DFS and DSS (p = .001) and OS (p = .002). After adjusting for confounders and prognostic factors, we found a significant difference between the treatment groups in LRC (adjusted HR = 2.88, 95%CI 1.35-6.16, p = .006). Within 100 days, 5 patients (5%) died from treatment-related toxicity in CRT group and 1 patient after surgery (p = .21).

Conclusions: Although surgery with adjuvant radiotherapy for advanced stage OCC results in favorable locoregional control, definitive (chemo)radiotherapy is a curative alternative in patients often considered beyond cure and should be considered when surgery is not feasible.
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http://dx.doi.org/10.1016/j.oraloncology.2017.11.006DOI Listing
December 2017

Bloom syndrome does not always present with sun-sensitive facial erythema.

Eur J Med Genet 2018 Feb 19;61(2):94-97. Epub 2017 Oct 19.

Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands. Electronic address:

Bloom syndrome is an autosomal recessive condition characterized by severe pre- and postnatal growth deficiency, immunodeficiency, an increased risk for malignancies, craniofacial dysmorphisms, and "typical" erythematous sun-sensitive skin lesions of the face. This facial rash has a butterfly-shaped distribution around the nose and is usually observed for the first time during the early years of life. Though reported as being a main feature of Bloom syndrome, there seems to be phenotypic variability regarding this facial skin rash among patients. It has been previously reported that in some individuals with Bloom syndrome these sun-sensitive lesions are less prominent or even absent. In this report we describe a 36 year old woman with short stature, microcephaly, several dysmorphisms, congenital hypothyroidism and premature ovarian failure. She was diagnosed with nasopharyngeal carcinoma at 36 years of age, only a few months after her consultation at the department of Clinical Genetics. Whole Exome Sequencing demonstrated that she had Bloom syndrome caused by a compound heterozygous mutation in BLM (c.2207_2212delinsTAGATTC; p.(Tyr736Leufs*5) and c.3681del; p.(Lys1227Asnfs*52)). She did not have facial sun-sensitive erythematous rash during childhood nor adulthood. We conclude that Bloom syndrome does not always present with erythematous sun-sensitive skin lesions of the face. We would like to underline that phenotypic variation regarding this "hallmark" feature of Bloom syndrome exists. Being aware of this might prevent a delay in diagnosing this rare short-stature syndrome and, subsequently, its potential clinical implications.
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http://dx.doi.org/10.1016/j.ejmg.2017.10.010DOI Listing
February 2018

Local control in sinonasal malignant melanoma: Comparing conventional to hypofractionated radiotherapy.

Head Neck 2018 Jan 16;40(1):86-93. Epub 2017 Oct 16.

Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands.

Background: The purpose of this study was to analyze the effect of fractionation schedule on local control in postoperative radiotherapy (RT) for sinonasal malignant melanoma.

Methods: Sixty-three patients who were treated with surgery and postoperative RT in 4 accredited head and neck cancer centers in the Netherlands between 1998 and 2013 were retrospectively studied. Outcomes with conventional fractionation (2-2.4 Gy per fraction; n = 27) were compared to hypofractionation (4-6 Gy per fraction; n = 36). The primary endpoint was local control and the secondary endpoint was toxicity.

Results: Comparable local control rates were found after 2 and 5 years (63% vs 64% and 47% vs 53%; P = .73 for, respectively, conventional fractionation vs hypofractionation). Local recurrences were predominantly present ipsilateral (92%) and within the irradiated volume (88%). Late toxicity grade ≥ 3 was observed in 2 of 63 patients, 1 patient in both groups.

Conclusion: Radiotherapy fractionation schedule did not influence the local control rate or the incidence of late toxicity in patients treated with surgery and RT for sinonasal malignant melanoma in this retrospective analysis. Due to this retrospective nature and the limited number of patients, strong recommendations cannot be made. Expected toxicity, patient convenience, and workload may be taken into account for the choice of fractionation schedule until conclusive evidence becomes available.
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http://dx.doi.org/10.1002/hed.24979DOI Listing
January 2018

Introducing navigation during melanoma-related sentinel lymph node procedures in the head-and-neck region.

EJNMMI Res 2017 Aug 17;7(1):65. Epub 2017 Aug 17.

Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Hospital, Albinusdreef 2, C2-S zone, 9600, 2300 RC, Leiden, the Netherlands.

Background: Intraoperative sentinel node (SN) identification in patients with head-and-neck malignancies can be challenging due to unexpected drainage patterns and anatomical complexity. Here, intraoperative navigation-based guidance technologies may provide outcome. In this study, gamma camera-based freehandSPECT was evaluated in combination with the hybrid tracer ICG-Tc-nanocolloid.

Materials And Methods: Eight patients with melanoma located in the head-and-neck area were included. Indocyanine green (ICG)-Tc-nanocolloid was injected preoperatively, whereafter lymphoscintigraphy and SPECT/CT imaging were performed in order to define the location of the SN(s). FreehandSPECT scans were generated in the operation room using a portable gamma camera. For lesion localization during surgery, freehandSPECT scans were projected in an augmented reality video-view that was used to spatially position a gamma-ray detection probe. Intraoperative fluorescence imaging was used to confirm the accuracy of the navigation-based approach and identify the exact location of the SNs.

Results: Preoperatively, 15 SNs were identified, of which 14 were identified using freehandSPECT. Navigation towards these nodes using the freehandSPECT approach was successful in 13 nodes. Fluorescence imaging provided optical confirmation of the navigation accuracy in all patients. In addition, fluorescence imaging allowed for the identification of (clustered) SNs that could not be identified based on navigation alone.

Conclusions: The use of gamma camera-based freehandSPECT aids intraoperative lesion identification and, with that, supports the transition from pre- to intraoperative imaging via augmented reality display and directional guidance.
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http://dx.doi.org/10.1186/s13550-017-0312-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5560283PMC
August 2017

Adjuvant photodynamic therapy in head and neck cancer after tumor-positive resection margins.

Laryngoscope 2018 03 8;128(3):657-663. Epub 2017 Aug 8.

Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Objective: In case of close or positive resection margins after oncological resection in head and neck surgery, additional treatment is necessary. When conventional options are exhausted, photodynamic therapy (PDT) can play a role in achieving clear margins. The purpose of the current study was to evaluate the clinical benefit of PDT as adjuvant therapy next to surgery with positive resection margins. The role of the time interval between surgery and PDT on survival outcomes also was investigated.

Study Design: Retrospective cohort analysis.

Methods: Adjuvant PDT was performed in patients with a malignancy in the head and neck region with close or positive resection margins who were not eligible for conventional treatment options. The primary endpoint was progression-free survival. Secondary endpoints were disease-free survival, overall survival, and optimal time interval between surgery and PDT.

Results: Fifty-four patients were treated with surgery followed by meta-tetrahydroxyphenylchlorin-mediated PDT. There was a large diversity in tumor location and histopathology, as well as in time interval between surgery and PDT. The 2-year progression-free survival rate was 30%; 2-year disease-free survival rate was 28%; and 2-year overall survival was 51%. Disease-free survival was significantly better when the time interval between surgery and PDT was ≥ 6 weeks (P = 0.02).

Conclusion: PDT can be applied as adjuvant therapy after surgery in cases of a malignancy with close or positive tumor resection margins. However, the clinical benefits are yet to be determined. There is a significantly better disease-free survival with a time interval between surgery and PDT of minimal 6 weeks.

Level Of Evidence: 4. Laryngoscope, 128:657-663, 2018.
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http://dx.doi.org/10.1002/lary.26792DOI Listing
March 2018

Contralateral regional recurrence after elective unilateral neck irradiation in oropharyngeal carcinoma: A literature-based critical review.

Cancer Treat Rev 2017 Sep 21;59:102-108. Epub 2017 Jul 21.

Department of Head and Neck Surgery, Netherlands Cancer Institute/Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

Background: The head and neck region has rich regional lymphatic network, with a theoretical risk on contralateral metastasis from oropharyngeal cancer (OPC). There is a long-standing convention to irradiate the great majority of these tumors electively to both sides of the neck to reduce the risk of contralateral regional failure (cRF), but this can induce significant toxicity. We aimed to identify patient groups where elective contralateral irradiation may safely be omitted.

Methods: PubMed and EMBASE were searched for original full-text articles in English with a combination of search terms related to the end points: cRF in OPC primarily treated by radiotherapy only to the ipsilateral neck and identifying predictive factors for increased incidence of cRF. The data from the identified studies were pooled, the incidence of cRF was calculated and the correlation with different predictive factors was investigated.

Results: Eleven full-text articles met the inclusion criteria. In these studies, 1116 patients were treated to the ipsilateral neck alone. The mean incidence of cRF was 2.42% (range 0-5.9%, 95% CI 1.6-3.5%). The incidence of cRF correlated only with T-stage (p=0.008), and involvement of midline (p=0.001). However, the significant correlation with T-stage can be explained by the very low incidence of cRF among T1 (0.77%), and disappeared when the incidence of cRF was compared between T2, T3,and T4 (p=0.344).

Conclusion: The incidence of cRF in patients with OPC is very low, with involvement of midline providing the most significant prognosticator. These results call for trials on unilateral elective irradiation in selected groups.
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http://dx.doi.org/10.1016/j.ctrv.2017.07.004DOI Listing
September 2017

Management of the clinically N0 neck in squamous cell carcinoma of the maxillary alveolus and hard palate.

Head Neck 2016 12 4;38(12):1794-1798. Epub 2016 Jul 4.

Department of Oral and Maxillofacial Surgery, University of Groningen, University Medical Center Groningen, The Netherlands.

Background: The purpose of this study was to evaluate active surveillance strategy in the clinically negative neck in maxillary squamous cell carcinoma (SCC).

Methods: One hundred fourteen consecutive patients diagnosed with oral maxillary SCC were analyzed retrospectively from 3 centers in The Netherlands. Analysis parameters included regional disease-free survival of N0 patients stratified for T classification, elective radiotherapy (RT) of the neck; and overall survival of the whole cohort, stratified by N classification; salvage neck surgery rates.

Results: Within the N0 cohort, 26.0% of the patients developed neck metastasis in the follow-up visits. Regional recurrence was not related to T classification or postoperative RT of the neck. Regional and locoregional recurrence were associated with diminished overall survival (p < .05). Regional metastasis was operable in 22 of 26 cases (85%). Only 1 patient presented with inoperable neck metastasis without local recurrence.

Conclusion: Watchful waiting was feasible in this cohort. If meticulous follow-up is not available, elective neck dissection is recommended. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1794-1798, 2016.
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http://dx.doi.org/10.1002/hed.24511DOI Listing
December 2016

(Near-Infrared) Fluorescence-Guided Surgery Under Ambient Light Conditions: A Next Step to Embedment of the Technology in Clinical Routine.

Ann Surg Oncol 2016 08 28;23(8):2586-95. Epub 2016 Mar 28.

Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands.

Background And Purpose: In open surgery procedures, after temporarily dimming the lights in the operation theatre, the Photo Dynamic Eye (PDE) fluorescence camera has, amongst others, been used for fluorescence-guided sentinel node (SN) biopsy procedures. To improve the clinical utility and logistics of fluorescence-guided surgery, we developed and evaluated a prototype modified PDE (m-PDE) fluorescence camera system.

Methods: The m-PDE works under ambient light conditions and includes a white light mode and a pseudo-green-colored fluorescence mode (including a gray-scaled anatomical background). Twenty-seven patients scheduled for SN biopsy for (head and neck) melanoma (n = 16), oral cavity (n = 6), or penile (n = 5) cancer were included. The number and location of SNs were determined following an indocyanine green-(99m)Tc-nanocolloid injection and preoperative imaging. Intraoperatively, fluorescence guidance was used to visualize the SNs. The m-PDE and conventional PDE were compared head-to-head in a phantom study, and in seven patients. In the remaining 20 patients, only the m-PDE was evaluated.

Results: Phantom study: The m-PDE was superior over the conventional PDE, with a detection sensitivity of 1.20 × 10(-11) M (vs. 3.08 × 10(-9) M) ICG in human serum albumin. In the head-to-head clinical comparison (n = 7), the m-PDE was also superior: (i) SN visualization: 100 versus 81.4 %; (ii) transcutaneous SN visualization: 40.7 versus 22.2 %; and (iii) lymphatic duct visualization: 7.4 versus 0 %. Findings were further underlined in the 20 additionally included patients.

Conclusion: The m-PDE enhanced fluorescence imaging properties compared with its predecessor, and provides a next step towards routine integration of real-time fluorescence guidance in open surgery.
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http://dx.doi.org/10.1245/s10434-016-5186-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927603PMC
August 2016

Dysgenetic polycystic disease of the minor and submandibular salivary glands.

Head Neck 2016 Jun 8;38(6):E2437-E2439. Epub 2016 Feb 8.

Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background: Dysgenetic polycystic salivary gland disease is a rare pathology. No case of minor salivary gland involvement has been reported in the literature.

Methods: A female patient presented with bilateral tumors of the parotid glands, bilateral submandibular gland enlargement, and multiple cystic lesions of the oral mucosa. MRI of the neck was performed along with fine-needle aspiration (FNA) of the parotid tumors and excisional biopsy of an oral lesion.

Results: Imaging and FNA findings of the parotid glands were suggestive of bilateral Warthin tumors. Excisional biopsy of the oral lesion revealed a minor salivary gland with histopathological features of dysgenetic polycystic salivary gland disease. Submandibular gland enlargement was also attributed to this rare entity based on the imaging characteristics.

Conclusion: This is the first report of dysgenetic polycystic salivary gland disease of the minor salivary glands, combined with involvement of the submandibular glands and bilateral Warthin tumors of the parotid gland. © 2016 Wiley Periodicals, Inc. Head Neck 38: E2437-E2439, 2016.
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http://dx.doi.org/10.1002/hed.24401DOI Listing
June 2016

Skin adnexal carcinoma of the head and neck: a retrospective study in a tertiary referral center.

Eur Arch Otorhinolaryngol 2015 Apr 16;272(4):1001-1010. Epub 2014 Oct 16.

Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

The objective of this study is to give more insight in the diagnosis, clinical course and therapy of skin adnexal carcinoma of the head and neck. Forty cases of skin adnexal carcinoma of the head and neck treated from 1977 to 2011 were identified by searching the hospitals cancer registration database. After pathology review by a pathologist specialized in skin cancer, 17 cases were excluded. A retrospective chart review of the remaining 23 patients was performed. Clinical course was recorded by endpoints including survival, loco-regional control and recurrence free survival. Prognostic factors considered for analysis were differentiation of the tumor and location of the tumor. Five-year overall survival (OS) was 78 % (95 % CI 61-100 %). Five-year recurrence free survival (RFS) was 58 % (95 % CI 40-84 %). Poor differentiation of the tumor significantly reduced OS (p = 0.002) and RFS (p = 0.01). Tumor location 'face' demonstrated a significantly better survival than other tumor locations (p < 0.001). Local recurrence occurred in five cases, regional metastasis was seen in seven patients, distant metastasis in three patients. Three cases with distant metastases died of disease. Based on the findings of this small group of patients in a tertiary referral center, we conclude that skin adnexal carcinoma is a very rare skin carcinoma that can behave locally aggressive but also has the potential for regional and distant metastasis. The recognition of skin adnexal carcinoma and subsequent wide excision in an early stage of the disease is of major importance for loco-regional control and survival.
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http://dx.doi.org/10.1007/s00405-014-3324-8DOI Listing
April 2015

Functional and aesthetic recontouring of free flap reconstructions of the head and neck region with microdebrider.

Kulak Burun Bogaz Ihtis Derg 2014 Mar-Apr;24(2):118-22

Department of Head and Neck Oncology and Surgery, Netherlands Cancer Institute, Antoni Van Leeuwenhoek Hospital, Plesmanlaan 121 1066CX, Amsterdan, Netherlands.

Free flaps have become standard of care for reconstruction of the head and neck defects following surgery. The bulkiness of the free flap reconstruction may cause aesthetically and functionally suboptimal results. Recontouring of the flaps with a microdebrider thinning the excessive subcutaneous fatty tissue provides an easy and safe solution to problems. In this article, we describe the recontouring technique with microdebrider in the light of aesthetic and functional examples.
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http://dx.doi.org/10.5606/kbbihtisas.2014.16013DOI Listing
October 2015

MR and CT based treatment planning for mTHPC mediated interstitial photodynamic therapy of head and neck cancer: description of the method.

Lasers Surg Med 2013 Oct 4;45(8):517-23. Epub 2013 Sep 4.

Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Background And Objective: Interstitial photodynamic therapy is a potentially important tool in the management of voluminous or deep-seated recurrent head and neck cancers.

Study Design/methods: The described treatment algorithm in this manuscript consists of the treatment simulation, implantation of light sources, verification, modification of the treatment plan if necessary, and illumination. The tumor is delineated on imaging sections (CT, MRI, and/or PET/CT) and the treatment is simulated by virtually introducing light sources to the tumor volume on specially modified brachytherapy software. This enables us to determine if the treatment is technically feasible, and information about approximate number and location of light sources necessary. Following implantation of catheters in which the light sources will be introduced, CT or MR scan is performed to verify the actual location of the implanted catheters. The verification-CT is imported to the software and co-registered with pre-treatment images to observe the deviations from the simulation. The simulation is run again with the actual position of the light sources to determine if any additional light sources are necessary and adaptation of the source length in order to cover the tumor volume (modification). Thereafter the tumor is illuminated.

Results: This method has the potential to help with identifying iPDT feasible patients by simulating before the actual treatment. The suboptimal placement of light sources can be identified and corrected. The simulations were documented and saved for subsequent evaluation of the technique.

Conclusion: The proposed technique can help standardize and document iPDT.
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http://dx.doi.org/10.1002/lsm.22174DOI Listing
October 2013

Management of the N0 neck in early stage oral squamous cell cancer: a modeling study of the cost-effectiveness.

Oral Oncol 2013 Aug 2;49(8):771-7. Epub 2013 Jun 2.

Department of Operating Rooms, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

Objectives: To assess the cost-effectiveness of five strategies for diagnosing and treating cT1-2N0 oral squamous cell cancer.

Materials And Methods: A Markov decision analytic model was used to evaluate the cost-effectiveness of (1) elective neck dissection (END), (2) watchful waiting (WW), (3) gene expression profiling (GEP) followed by neck dissection (ND) or WW, (4) sentinel lymph node (SLN) procedure followed by ND or WW, and (5) GEP and SLN (for positive GEP) followed by ND or WW. Uncertainty was addressed using one-way and probabilistic sensitivity analyses.

Results: Base-case analysis showed that SLN procedure followed by ND or WW was the most effective and most cost effective strategy. Compared with direct END the incremental cost effectiveness ratio was €3356 per QALY gained. Uncertainty analysis showed that the model was sensitive to changes in assumed occult metastases incidence and utility values. SLN was found to have the highest probability (66%) of being cost-effective of the five strategies, at a willingness to pay of €80,000 per QALY.

Conclusions: Given the current evidence and costs the SLN procedure followed by ND or WW appears to be the most cost effective strategy for diagnosing and treating oral squamous cell cancer patients. Our model provides the foundation for future diagnostic and therapeutic research in this field and shows that further information on quality of life in this population is highly valuable.
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http://dx.doi.org/10.1016/j.oraloncology.2013.05.001DOI Listing
August 2013

mTHPC-mediated photodynamic therapy of early stage oral squamous cell carcinoma: a comparison to surgical treatment.

Ann Surg Oncol 2013 Sep 19;20(9):3076-82. Epub 2013 May 19.

Department of Oral and Maxillofacial Surgery, Division of Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Background: mTHPC-mediated photodynamic therapy (PDT) is used for treatment of early head and neck squamous cell carcinoma. This study is a retrospective comparison of PDT with transoral surgery in the treatment of early primary squamous cell carcinoma of the oral cavity/oropharynx.

Methods: PDT data were retrieved from four study databases; surgical results were retrieved from our institutional database. To select similar primary tumors, infiltration depth was restricted to 5 mm for the surgery group. A total of 126 T1 and 30 T2 tumors were included in the PDT group, and 58 T1 and 33 T2 tumors were included in the surgically treated group.

Results: Complete response rates with PDT and surgery were 86 and 76% for T1, respectively, and for T2 63 and 78%. Lower local disease-free survival for PDT compared to surgery was found. However, when comparing the need for local retreatment, no significant difference for T1 tumors was found, while for T2 tumors surgery resulted in significantly less need for local retreatment. No significant differences in overall survival between surgery and PDT were observed.

Conclusions: PDT for T1 tumors results in a similar need for retreatment compared to surgery, while for T2 tumors PDT performs worse. Local disease-free survival for surgery is better than for PDT. This may be influenced by the benefit surgery has of having histology available. This allows an early decision on reintervention, while for PDT one has to follow a wait-and-see policy. Future prospective studies should compare efficacy as well as morbidity.
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http://dx.doi.org/10.1245/s10434-013-3006-6DOI Listing
September 2013

Primary treatment results of Nasopharyngeal Carcinoma (NPC) in Yogyakarta, Indonesia.

PLoS One 2013 10;8(5):e63706. Epub 2013 May 10.

Department of Head and Neck Oncology and Surgery, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Introduction: Nasopharyngeal Carcinoma (NPC) is a major health problem in southern and eastern Asia. In Indonesia NPC is the most frequent cancer in the head and neck area. NPC is very sensitive to radiotherapy resulting in 3-year disease-free and overall survival of approximately 70% and 80%, respectively. Here we present routine treatment results in a prospective study on NPC in a top referral; university hospital in Indonesia.

Methods: All NPC patients presenting from September 2008 till January 2011 at the ear, nose and throat (ENT) department of the Dr. Sardjito General Hospital, Universitas Gadjah Mada, Yogyakarta, Indonesia, were possible candidates. Patients were included if the biopsy was a histological proven NPC without distant metastasis and were assessed during counselling sessions prior to treatment, as being able to complete the entire treatment.

Results: In total 78 patients were included for treatment analysis. The median time between diagnosis and start of radiotherapy is 120 days. Forty-eight (62%) patients eventually finished all fractions of radiotherapy. The median duration of the radiotherapy is 62 days for 66 Gy. Median overall survival is 21 months (95% CI 18-35) from day of diagnosis.

Conclusion: The results presented here reveal that currently the treatment of NPC at an Indonesian hospital is not sufficient and cannot be compared to the treatment results in literature. Main reasons for these poor treatment results are (1) a long waiting time prior to the start of radiotherapy, (2) the extended overall duration of radiotherapy and (3) the advanced stage of disease at presentation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0063706PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3651124PMC
December 2013

A matched cohort comparison of mTHPC-mediated photodynamic therapy and trans-oral surgery of early stage oral cavity squamous cell cancer.

Eur Arch Otorhinolaryngol 2013 Mar 7;270(3):1093-7. Epub 2012 Jul 7.

Department of Head and Neck Surgery and Oncology, Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Photodynamic therapy (PDT) of early stage oral cavity tumors have been thoroughly reported. However, statistical comparison of PDT to the surgical treatment is not available in published literature. We have identified and matched cohorts of patients with early stage oral cavity cancers undergoing surgery (n = 43) and PDT (n = 55) from a single institute experience. The groups are matched demographically and had the same pre-treatment screening and follow-up schedule. Both groups consisted only of tumors thinner than 5 mm to ensure comparability. The endpoints were local disease free survival, disease free survival, overall survival and response to initial treatment. Local disease free survival at 5 years were 67 and 74 % for PDT and surgery groups, respectively [univariate HR = 1.9 (p = 0.26), multivariable HR = 2.7 (p = 0.13)]. Disease free survival at 5 years are 47 and 53 % for PDT and surgery groups, respectively [univariate HR = 0.8 (p = 0.52), multivariable HR = 0.75 (p = 0.45)]. Overall survival was 83 and 75 % for PDT and surgery groups, respectively [(univariate HR = 0.5 (p = 0.19), multivariable HR = 0.5 (p = 0.17)]. In the PDT group, six patients (11 %) and in the surgery group 11 patients (26 %) had to receive additional treatments after the initial. All of the tested parameters did not have statistical significant difference. Although there is probably a selection bias due to the non-randomized design, this study shows that PDT of early stage oral cavity cancer is comparable in terms of disease control and survival to trans-oral resection and can be offered as an alternative to surgical treatment.
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http://dx.doi.org/10.1007/s00405-012-2104-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3580137PMC
March 2013

A rare late complication after concomitant chemoradiation of an oropharyngeal tumor: cervical necrotizing fasciitis.

Kulak Burun Bogaz Ihtis Derg 2012 Mar-Apr;22(2):105-8

Department of Head and Neck Surgery and Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

Chemoradiation is increasingly being used to treat locally advanced head and neck carcinomas. Possible rare complications of this treatment modality have begun to appear, as the number of treated patients increase. In this report, we present a case who underwent chemoradiation due to T3N3M0 tonsil cancer and developed necrotizing fasciitis of the neck at seven months following treatment. The patient recovered fully after treatment with surgical debridement with pectoralis major flap reconstruction and intravenous antibiotherapy.
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http://dx.doi.org/10.5606/kbbihtisas.2012.019DOI Listing
August 2012

Concomitant radio- and fluorescence-guided sentinel lymph node biopsy in squamous cell carcinoma of the oral cavity using ICG-(99m)Tc-nanocolloid.

Eur J Nucl Med Mol Imaging 2012 Jul 18;39(7):1128-36. Epub 2012 Apr 18.

Department of Nuclear Medicine, The Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.

Purpose: For oral cavity malignancies, sentinel lymph node (SLN) mapping is performed by injecting a radiocolloid around the primary tumour followed by lymphoscintigraphy. Surgically, SLNs can then be localized using a handheld gamma ray detection probe. The aim of this study was to evaluate the added value of intraoperative fluorescence imaging to the conventional radioguided procedure. For this we used indocyanine green (ICG)-(99m)Tc-nanocolloid, a hybrid tracer that is both radioactive and fluorescent.

Methods: Fourteen patients with oral cavity squamous cell carcinoma were peritumourally injected with ICG-(99m)Tc-nanocolloid. SLNs were preoperatively identified with lymphoscintigraphy followed by single photon emission computed tomography (SPECT)/CT for anatomical localization. During surgery, SLNs were detected with a handheld gamma ray detection probe and a handheld near-infrared fluorescence camera. Pre-incision and post-excision imaging with a portable gamma camera was performed to confirm complete removal of all SLNs.

Results: SLNs were preoperatively identified using the radioactive signature of ICG-(99m)Tc-nanocolloid. Intraoperatively, 43 SLNs could be localized and excised with combined radio- and fluorescence guidance. Additionally, in four patients, an SLN located close to the primary injection site (in three patients this SLN was located in level I) could only be intraoperatively localized using fluorescence imaging. Pathological analysis of the SLNs revealed a metastasis in one patient.

Conclusion: Combined preoperative SLN identification and intraoperative radio- and fluorescence guidance during SLN biopsies for oral cavity cancer proved feasible using ICG-(99m)Tc-nanocolloid. The addition of fluorescence imaging was shown to be of particular value when SLNs were located in close proximity to the primary tumour.
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http://dx.doi.org/10.1007/s00259-012-2129-5DOI Listing
July 2012
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