Baris Karakullukcu

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

PurposeFor 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)‐99mTc‐nanocolloid, a hybrid tracer that is both radioactive and fluorescent.MethodsFourteen patients with oral cavity squamous cell carcinoma were peritumourally injected with ICG-99mTc-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.ResultsSLNs were preoperatively identified using the radioactive signature of ICG-99mTc-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.ConclusionCombined preoperative SLN identification and intraoperative radio- and fluorescence guidance during SLN biopsies for oral cavity cancer proved feasible using ICG-99mTc-nanocolloid. The addition of fluorescence imaging was shown to be of particular value when SLNs were located in close proximity to the primary tumour.

Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to identify the success rates for each subgroup according to T stage, primary or non-primary treatment and subsites. In total, 170 patients with 226 lesions are treated with PDT. From these lesions, 95 are primary neoplasms, 131 were non-primaries (recurrences and multiple primaries). The overall response rate is 90.7% with a complete response rate of 70.8%. Subgroup analysis identified oral tongue, floor of mouth sites with more favorable outcome. PDT has more favorable results with certain subsites and with previously untreated lesions. However, PDT can find its place for treating lesions in previously treated areas with acceptable results.

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

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.

mTHPC mediated interstitial photodynamic therapy of recurrent nonmetastatic base of tongue cancers : Development of a new method

Interstitial photodynamic therapy (iPDT) can be an option in the management of locally recurrent base of tongue cancer after (chemo)radiation treatment. The purpose of the current study was to develop a technique to implant light sources into the tumor tissue.

Photodynamic therapy in the therapy for recurrent/persistent nasopharyngeal cancer

To determine the efficacy of Photodynamic therapy of patients with recurrent Nasopharyngeal Carcinoma we reviewed all available literature.Since the treatment options for recurrent or persistent Nasopharyngeal Carcinoma are limited, the survival rates poor and the complications severe; there is definitely a place for alternative treatment modalities with more efficacy and less morbidity. Photodynamic therapy (PDT) has the potential to be a very effective local treatment modality for recurrent or persistent nasopharyngeal cancer, without the severe side effects seen with re-irradiation. This review shows all reported results of Photodynamic therapy in the treatment for Nasopharyngeal Carcinoma.

Primary Treatment Results of Nasopharyngeal Carcinoma (NPC) in Yogyakarta, Indonesia

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.

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

Interstitial photodynamic therapy is a potentially important tool in the management of voluminous or deep‐seated recurrent head and neck cancers.

Temoporfin mediated photodynamic therapy in patients with local persistent and recurrent nasopharyngeal carcinoma after curative radiotherapy: A feasibility study

BACKGROUND The treatment of persistent and recurrent nasopharyngeal carcinoma (NPC) remains a challenge, especially in Indonesia. We investigated the safety and efficacy of temoporfin mediated photodynamic therapy (PDT) for patients with local persistent and recurrent NPC. MATERIAL AND METHODS Twenty-two patients with persistent and recurrent NPC (maximum tumor depth < 10mm) underwent PDT under local anesthesia with use of a nasopharyngeal light applicator. Three different drug doses and light intervals have been administered: treatment arm A: 0.15 mg/kg Foscan; 96 h drug-light interval; B: drug dose of 0.10 mg/, 48 h drug-light interval; C: drug dose of 0.075 mg/kg, 24 h drug-light interval. Toxicity was measured by using the CTCAE 3.1 scale. RESULTS Arm A consisted of eight patients, arms B and C consisted of seven patients. The treatment procedure was well tolerable under local anesthesia. The most common grade III toxicities for all groups is headache (n = 7; 33%). No grade IV toxicity was seen. One patient died 2 days after treatment due to a misdiagnosed pneumonia. In 17 of the 22 patients a biopsy was performed after 40 weeks and showed no tumor in all biopsies. Arm A seems, in addition to comparable toxicity, clinically more effective than arms B and C. CONCLUSION The present study demonstrated that temoporfin mediated photodynamic therapy is a relatively simple technique that can be utilized to treat residual or recurrent nasopharyngeal cancer, restricted locally to the nasopharynx.

Monitoring microcirculatory alterations in oral squamous cell carcinoma following photodynamic therapy

BACKGROUND One of the mechanisms through which photodynamic therapy (PDT) is thought to elicit tumour destruction is by producing microvascular damage and obstruction of nutritive blood flow. The aim of this study was to directly monitor and quantify microcirculatory changes following tissue illumination by PDT for oral squamous cell carcinoma. METHODS Ten consecutive patients receiving PDT for a carcinoma in situ, a T1 or T2 tumour in the oral cavity without evidence of lymph node metastasis were selected for this study. Tumour and marginal healthy mucosa total capillary density (TCD) and functional capillary density (FCD) inside the field of illumination were measured and compared using sidestream dark-field (SDF) imaging prior to tissue illumination, immediately after PDT, and again after 15min. RESULTS Baseline mean tumour TCD was 21.2±5capillaries per square millimetres (cpll/mm²) and 24.9±19cpll/mm² in the surrounding marginal healthy tissue; there were no significant differences between tumour and healthy tissue or time points. Comparisons between baseline and post-illumination time points revealed significant differences in both tumour and healthy tissue FCD (P<0.05). No significant differences in FCD were observed between the two tissues. CONCLUSIONS Our findings using SDF imaging demonstrate that PDT significantly attenuates tumour and marginal healthy tissue perfusion by directly disrupting the functionality of the microcirculation.

The use of photodynamic therapy as adjuvant therapy to surgery in recurrent malignant tumors of the paranasal sinuses

BACKGROUND Malignant tumors of paranasal sinuses and anterior skull base recur frequently after surgery and adjuvant radiotherapy. The vicinity of essential structures limits additional treatment options, such as salvage surgery and re-radiation. We report the feasibility of photodynamic therapy (PDT) as an adjuvant treatment to surgery. METHODS Fifteen patients with recurrent tumors of the paranasal sinuses were treated with mtetrahydroxyphenylchlorin (mTHPC) mediated PDT as an adjuvant treatment to salvage surgery. All patients had previously curative radiotherapy. The treated tumors were squamous cell cancer (8), adenocarcinoma (3), undifferentiated carcinoma (2), adenoid cystic carcinoma (1) and radiotherapyinduced sarcoma (1). In five cases there was extension to the skull base. Two approaches of surgery where used, namely in eight cases an open approach, in the other seven endoscopic approach. Complete macroscopic resection with microscopic tumor positive margins was possible in three patients. The remaining twelve patients received debulking surgery followed by PDT. RESULTS None of the patients had cerebrospinal fluid leak, meningitis, major bleeding or vision loss. Four patients developed temporary diplopia due to edema of the medial rectus muscle, one patient suffered from extensive necrosis leading to oro-nasal fistula. Complete response was observed in five patients. CONCLUSION Photodynamic therapy can be used with relative safety as adjuvant therapy to surgery in recurrent tumors of the paranasal sinuses and the anterior skull base where complete resection is not achievable.