Adjuvant Photodynamic Therapy Research Articles

Yeast Nanoparticle‐powered Tumor Photodynamic‐Immunotherapy

Photodynamic therapy (PDT) uses a combination of light and a photosensitizing agent to destroy cancerous cells. However, the PDT alone often insufficient to elicit an effective anti-tumor response due to various factors including insufficient ROS generation and the weak induced immune response. Here, we report yeast nanoparticles (YNPs) loaded with aggregation-induced emission (AIE) photosensitizer QMC12 (YNP-QMC) for enhanced photodynamic-immunotherapy in animal models. YNPs have a strong immune adjuvant effect which could significantly activate various APCs and reverse the immunosuppressive microenvironment at tumor and tumor-draining lymph nodes (TDLNs) sites. More importantly, YNP-QMC can be attached with tumor cell antigens released from dying cells after PDT. This antigen attached nanoparticle can efficiently migrate to tumor-draining lymph nodes and activate an antigen-specific systemic antitumor immunity. In combination with anti-PD-L1, this strategy could promote the elimination of primary tumors and inhibit the growth of distant tumors. Thus, our AIE photosensitizer and adjuvant YNP-powered PDT strategy provides a simple way to enhance efficacy of PDT.

Using mixed reality technique combines multimodal imaging signatures to adjuvant glioma photodynamic therapy.

Photodynamic therapy (PDT) promotes significant tumor regression and extends the lifetime of patients. The actual operation of PDT often relies on the subjective judgment of experienced neurosurgeons. Patients can benefit more from precisely targeting PDT's key operating zones. We used magnetic resonance imaging scans and created 3D digital models of patient anatomy. Multiple images are aligned and merged in STL format. Neurosurgeons use HoloLens to import reconstructions and assist in PDT execution. Also, immunohistochemistry was used to explore the association of hyperperfusion sites in PDT of glioma with patient survival. We constructed satisfactory 3D visualization of glioma models and accurately localized the hyperperfused areas of the tumor. Tumor tissue taken in these areas was rich in CD31, VEGFA and EGFR that were associated with poor prognosis in glioma patients. We report the first study using MR technology combined with PDT in the treatment of glioma. Based on this model, neurosurgeons can focus PDT on the hyperperfused area of the glioma. A direct benefit was expected for the patients in this treatment. Using the Mixed Reality technique combines multimodal imaging signatures to adjuvant glioma PDT can better exploit the vascular sealing effect of PDT on glioma.

Antibacterial efficiency of adjuvant photodynamic therapy and high-power diode laser in the treatment of young permanent teeth with chronic periapical periodontitis. A prospective clinical study.

The study aimed at determining antibacterial efficiency of adjuvant photodynamic therapy (PDT) and high-power diode laser (DL) in the treatment of chronic periapical periodontitis (CPP) in young permanent teeth. Forty-four young permanent teeth with CPP were randomly divided into three groups (PDT, DL and control). Each tooth underwent standard chemo-mechanical treatment, while within tested groups was additionally treated by PDT or DL. Bacterial identification and quantification were provided by MALDI-TOF spectrometry and plate counting assay, performed after accessing the canal, following chemo-mechanical preparation, and after PDT or DL procedure where applicable. Thirty-nine young permanent teeth with CCP (patients age 9.77±1.43) completed the study. Before the treatments, 202 isolates belonging to 13 genera/species, including Streptococcus (36), Actinomyces (34), Peptostreptococcus micros (27), Veillonella (25) and Enterococcus faecalis (22), were recovered. Chemo-mechanical treatment reduced CFU count in the all three groups (p < 0.001), but complete eradication was not observed for any of isolated species. Adjuvant PDT and DL completely eradicated isolates of 8 and 6 bacterial genera/species, resulting in complete bacterial elimination from 53.8% and 30.8% of root canals, respectively. In the rest canals, total Δlog CFUs were 4.71 and 4.58. The results indicated that both PDT and DL could be performed as adjuvants to standard endodontic treatment of the young permanent teeth with CPP.

Photodynamic therapy (PDT) as adjuvant treatment to brachytherapy for amelanotic choroidal melanoma.

To evaluate the effect of photodynamic therapy (PDT) as adjuvant treatment, after brachytherapy, in posterior amelanotic choroidal melanomas. Six patients with posterior amelanotic choroidal melanoma underwent brachytherapy treatment. Tumour response was assessed by fundus examination, fundus photography and A-B scan ultrasonography. The residual tumours were treated with adjuvant PDT performed with infusion of verteporfin intravenously at 6 mg/m2 body surface area. Five minutes after infusion, a 689 nm laser was applied with a light dose of 100 J/cm2 over an interval of 166 s. At a median follow-up after brachytherapy of 17.5 months (IQR 16.2-22.5, range 5-42 months), tumours showed a partial reduction of tumour thickness (22.5% as compared to baseline value) and persistent low internal reflectivity at A-B scan ultrasonography. Supplementary photodynamic treatment resulted in complete resolution of the lesion with marked decrease of elevation . Mean decrease in thickness after PDT was 49.9% with respect to previous brachytherapy treatment 22.5% (p = 0.007). The results was achieved within a median period of 4 months (range 2-4 months) after PDT, and there has been no recurrence after a median follow-up of 84.7 months ± 18.7 (range 59 to 107 months). Combined treatment of brachytherapy and adjuvant PDT in amelanotic uveal melanoma seems to be favourable with regard to complete and rapid tumour regression.

Surgery combined with photodynamic therapy versus surgery alone for the treatment of non-melanoma skin cancer and actinic keratosis: A retrospective cohort study.

Photodynamic therapy (PDT) is an effective treatment for some non-melanoma skin cancers (NMSC) and actinic keratosis. To compare recurrence-free survival (RFS) rates between surgery alone and surgery with postoperative PDT in patients with NMSC in China. This retrospective cohort study included patients with pathologically confirmed NMSC or actinic keratosis treated by surgical excision with/without PDT. A total of 125 patients were included, including 72 patients (43 females) aged 57-75 years in the surgery alone group and 53 patients (32 females) aged 61-76 years in the surgery+PDT group. The most common NMSC types were squamous cell carcinoma and basal cell carcinoma, the most common lesion site was the head and neck, and the vast majority of patients had a primary disease and solitary lesions. There were no significant differences between groups in baseline characteristics. RFS rates in the surgery alone and surgery+PDT groups were, respectively, 100.0% and 98.1% at 1week, 98.6% and 98.1% at 4 weeks, 97.2% and 98.1% at 8 weeks, 97.2% and 98.1% at 12 weeks, and 90.3% and 90.4% at 24 weeks, with no significant differences between groups. Adjuvant PDT after surgical excision of NMSC or actinic keratosis does not provide short-term improvement in RFS, but the results need to be confirmed by a formal randomized controlled trial.

Long term outcome of adjuvant photodynamic therapy after cyberknife radiotherapy for choroidal melanoma

PurposeTo report the outcome of photodynamic therapy (PDT) for choroidal melanoma as adjuvant treatment with CyberKnife radiotherapy. DesignRetrospective interventional case series. MethodsStandard-fluence PDT using verteporfin. Outcome measuresRegression of tumor; resolution of subretinal fluid (SRF); change in best-corrected visual acuity (BCVA), and complications of PDT. ResultsThe study included 16 choroidal melanomas (3 pigmented, 4 lightly pigmented, 9 amelanotic) treated with adjuvant PDT after CyberKnife radiotherapy. The mean follow up time was 45.5 months after the initial PDT. 13 patients improved completely with PDT sessions and growth was seen in 3 patients. There was seen completely resolution in SRF in 10 eyes, partial resolution in 3 eyes, and stable in 3 eyes. The mean thickness of tumors was 3.9 mm before PDT and 2.3 mm after PDT. Retina pigment epithelium atrophy in 3 patients and subretinal hemorrhage in 1 patient were seen as complication of PDT. Three patients underwent enucleation for recurrence in the tumor. There was not a higher rate of change in BCVA after PDT (37.5% stable; 25% increase; 37.5% decrease. Poor final visual acuity associated with worse initial visual acuity, proximity of the tumor to the foveola and optic disc, and radiation complications. ConclusionsPDT seems to offer a good option for posterior pole choroidal melanoma as adjuvant therapy in suitable cases. Future prospective studies with larger number of patients and with longer follow-up are needed to further investigation.

Theranostic PSMA ligands with optimized backbones for intraoperative multimodal imaging and photodynamic therapy of prostate cancer

IntroductionThe first generation ligands for prostate-specific membrane antigen (PSMA)–targeted radio- and fluorescence-guided surgery followed by adjuvant photodynamic therapy (PDT) have already shown the potential of this approach. Here, we developed three new photosensitizer-based dual-labeled PSMA ligands by crucial modification of existing PSMA ligand backbone structures (PSMA-1007/PSMA-617) for multimodal imaging and targeted PDT of PCa.MethodsVarious new PSMA ligands were synthesized using solid-phase chemistry and provided with a DOTA chelator for 111In labeling and the fluorophore/photosensitizer IRDye700DX. The performance of three new dual-labeled ligands was compared with a previously published first-generation ligand (PSMA-N064) and a control ligand with an incomplete PSMA-binding motif. PSMA specificity, affinity, and PDT efficacy of these ligands were determined in LS174T-PSMA cells and control LS174T wildtype cells. Tumor targeting properties were evaluated in BALB/c nude mice with subcutaneous LS174T-PSMA and LS174T wildtype tumors using µSPECT/CT imaging, fluorescence imaging, and biodistribution studies after dissection.ResultsIn order to synthesize the new dual-labeled ligands, we modified the PSMA peptide linker by substitution of a glutamic acid into a lysine residue, providing a handle for conjugation of multiple functional moieties. Ligand optimization showed that the new backbone structure leads to high-affinity PSMA ligands (all IC50 < 50 nM). Moreover, ligand-mediated PDT led to a PSMA-specific decrease in cell viability in vitro (P < 0.001). Linker modification significantly improved tumor targeting compared to the previously developed PSMA-N064 ligand (≥ 20 ± 3%ID/g vs 14 ± 2%ID/g, P < 0.01) and enabled specific visualization of PMSA-positive tumors using both radionuclide and fluorescence imaging in mice.ConclusionThe new high-affinity dual-labeled PSMA-targeting ligands with optimized backbone compositions showed increased tumor targeting and enabled multimodal image-guided PCa surgery combined with targeted photodynamic therapy.

Adjuvant Photodynamic Therapy, Mediated via Topical Versus Systemic Administration of 5-Aminolevulinic Acid for Control of Murine Mammary Tumor after Surgical Resection.

Treatment de-escalation is sought in the management of precursor lesions of early stage breast cancer, driving the appeal of adjuvant modalities to lumpectomy that reduce toxicity and minimally detract from patient quality of life. We investigate photodynamic therapy (PDT), with the photosensitizing prodrug, 5-aminolevulinic acid (ALA), as adjuvant therapy to complete resection of murine mammary tumor (propagated from TUBO cells). ALA was delivered either systemically (oral, 250 mg kg-1 ) at 5 h before 632 nm illumination or topically (20% solution) to the resection site at 10 min before light delivery to 135 J cm-2 . Treatment with either oral-ALA-PDT (oALA-PDT) or topical-ALA-PDT (tALA-PDT) to the mammary fat pad after TUBO complete resection (CR) produced long-term tumor control with 90-day complete response rates of 21% and 32%, respectively, compared to control rates of 0-5% in mice receiving only CR. Thus, CR/tALA-PDT was equipotent to CR/oALA-PDT despite ~10-fold lower levels of ALA-induced protoporphyrin XI as photosensitizer after topical versus oral-ALA administration. CR/oALA-PDT produced more vascular damage, greater proportion of tissue-resident neutrophils and stronger inflammation when compared to CR/tALA-PDT. Collectively, these data provide rationale for ongoing investigation of ALA-PDT as adjuvant therapy after lumpectomy for increased probability of local control in the treatment of breast cancer.

Abstract B27: Photoluminescent nanoconjugates for molecular imaging of bladder cancer

Abstract Introduction and Objectives: Despite multiple resections and long-term chemo and immunotherapy, most non-muscle invasive bladder cancer patients suffer from recurrence or progression leading to cystectomy and a less favorable outcome. Possible reasons for that are incomplete resection and reimplantation of cancer cells, which could be prevented by improved resection and adjuvant therapy. Our objective was to develop a targeted drug for detection, fluorescence-guided resection, and deep-penetrating adjuvant photodynamic therapy of urothelial carcinoma (UC). The agent was based on upconversion nanoparticles (UCNP), which can carry a photosensitizer and can transform deep-penetrating near-infrared light into high-energy visible light, demanded for tumor visualization and for production of reactive oxygen species in the photosensitizer. At this stage, we aimed to select an antibody that could be attached to UCNPs to deliver them to UC cells. Methods: We produced silica-coated UCNP of the composition NaYF4:Yb,Er amenable for conjugation with biomolecules. An anti-Glypican-1 (GPC-1) monoclonal antibody MIL-38 (Glytherix Ltd., Sydney, Australia), was chosen for targeted delivery of the nanoparticles as it had previously demonstrated affinity towards bladder cancer. UCNPs were conjugated with MIL-38 by using a fusion protein Linker-Protein G (LPG). Finally, to investigate targeted binding and molecular specificity of these nanoconjugates, we incubated them with GPC-1 positive and GPC-1 negative cells. The role of MIL-38 in targeted delivery of nanoconjugates was also validated by incubation of GPC-1 positive T24 cells with nanoparticles coupled to an isotype control antibody and without an antibody. Results: Targeted upconversion nanoconjugates UCNP-LPG-MIL-38 labeled almost 90% of T24 cells with high expression of GPC-1 and only 23.2% of C3 cells with low expression of this antigen, demonstrating high molecular selectivity and specificity. Incubation of T24 cells with nanoconjugates linked with a control antibody and without antibody resulted in labeling of 19.8% and 26.2%, respectively, demonstrating the role of MIL-38 in targeted delivery of these nanoconjugates. As a result of the labeling, mean photoluminescence of cells in targeted group was from five to eight times stronger than in control groups, allowing for easy identification of positive cells with low background autofluorescence. Conclusions: These results highlight the potential of these nanoconjugates for the diagnosis and therapy of UC, as they can bind to Glypican-1-positive BC cells and cause their bright photoluminescence, which could be used for detection of tumors and activation of photosensitizers. It was also confirmed that monoclonal antibody MIL-38 has high potential to be applied in experimental diagnosis, drug delivery, and targeted therapy of UC, as it mediated targeted binding of upconversion photoluminescent nanoconjugates to Glypican-1-positive UC cells. Citation Format: Liuen Liang, Andrew Care, Anwar Sunna, Douglas Campbell, Bradley Walsh, Andrei Zvyagin, David Gillatt, Dmitry Polikarpov. Photoluminescent nanoconjugates for molecular imaging of bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr B27.

Cabozantinib Inhibits Photodynamic Therapy-Induced Auto- and Paracrine MET Signaling in Heterotypic Pancreatic Microtumors.

Extensive desmoplasia is a hallmark of pancreatic ductal adenocarcinoma (PDAC), which frequently associates with treatment resistance. Recent findings indicate that a combination of photodynamic therapy and the multi-kinase inhibitor cabozantinib achieved local tumor control and a significant decrease in tumor metastases in preclinical PDAC models, but the underlying therapeutic mechanisms remain unclear. This study elucidates the molecular basis of this multi-agent regimen, focusing on the role of MET signaling. Since MET activation stems from its interaction with hepatocyte growth factor (HGF), which is typically secreted by fibroblasts, we developed heterotypic PDAC microtumor models that recapitulate these interactions. In these models, MET signaling can be constitutively activated through paracrine and autocrine mechanisms. Photodynamic therapy caused significant elevations in HGF secretion by fibroblasts, suggesting it plays a complex role in the modulation of the paracrine HGF–MET signaling cascade in desmoplastic tumors. Blocking MET phosphorylation with adjuvant cabozantinib caused a significant improvement in photodynamic therapy efficacy, most notably by elevating spheroid necrosis at low radiant exposures. These findings highlight that adjuvant photodynamic therapy can augment chemotherapy efficacies, and potentially achieve improved management of desmoplastic PDAC in a more tolerable manner.

Photodynamic therapy of intradermal metastatic breast cancer (literature review)

In recent years, an increase in the incidence of breast cancer has been observed throughout the world, and in 20% of cases, with the development of intradermal metastases. The possibilities of surgical and radiation treatment of intradermal breast metastases are quite limited, and the effectiveness of polychemotherapy using standard regimens does not exceed 22–27%, while the period of remission, in general, is only 2–3 months. Photodynamic therapy (PDT) is a promising treatment for intradermal metastases of breast cancer. The experience of using PDT in this nosology is quite limited, but the results show its high efficiency and safety. Thus, several Russian studies are devoted to assessing the effectiveness of PDT of intradermal breast metastases with Photolon, a chlorin series photosensitizer. According to the authors, the therapeutic effect was achieved in 85–97% of patients (the percentage of patients with full and partial effect was 73–85%). Studies on the effectiveness of PDT in patients with the same nosology using the Photosens photosensitizer show a slightly lower effectiveness – the therapeutic effect was achieved in 81.8% of cases, while the proportion of patients with full and partial effect was only about 50%. Several studies have been carried out abroad on models of metastatic breast cancer using new photosensitizers (e.g. sodium sinoporphyrin) and new combined PDT regimens (e.g. adjuvant PDT with fluorouracil or Capecitabine). The obtained results demonstrate the promise of new approaches: PDT with sodium sinoporphyrin inhibited the growth of both the tumor itself and its metastases; the use of adjuvant regimens led to an increase in the tumor cells differentiation in the animal model, the cessation of tumor and metastatic foci growth.

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

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. Retrospective cohort analysis. 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. 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). 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. 4. Laryngoscope, 128:657-663, 2018.

Efficiency of photodynamic therapy in the treatment of peri-implantitis: A three-month randomized controlled clinical trial

Peri-implantitis is an inflammatory lesion of peri-implant tissues. Eradication of the causative bacteria and decontamination of the implant surface is essential in achieving predictable and stabile clinical results. Photodynamic therapy (PDT) is non-invasive adjuvant therapeutic method to surgery in the treatment of bacterial infection. The aim of this study was to evaluate early clinical and microbiological outcomes of periimplantitis after surgical therapy with adjuvant PDT. Fifty-two diagnosed peri-implantitis sites were divided into two groups. PDT was used for decontamination of implant surface in the study group; in the control group, chlorhexidine gel (CHX) followed by saline irrigation was applied. Several clinical parameters were recorded before the treatment (baseline values) and three months after surgical treatment. Samples for microbiological identification were collected before therapy, during the surgical therapy (before and after decontamination of implant surface), and three months thereafter, and analyzed with identification systems using biochemical analysis. The use of PDT resulted in significant decrease of bleeding on probing in comparison to CHX (p < 0.001). It showed significant decontamination of implant surfaces with complete elimination of anaerobic bacteria immediately after surgical procedure and three months later. The results indicate that PDT can be used as an adjuvant therapy to surgery for decontamination of implant surface and surrounding peri-implant tissues within the treatment of peri-implantitis.

56. Adjuvant photodynamic therapy using intravesically administered hematoporphyrin derivative for non-muscle invasive bladder cancer: 15 years follow-up results

56. Adjuvant photodynamic therapy using intravesically administered hematoporphyrin derivative for non-muscle invasive bladder cancer: 15 years follow-up results

How to access photodynamic therapy for bile duct carcinoma.

Photodynamic therapy (PDT) is a promising treatment option for local control of remnant cancer after surgical resection or biliary stenosis by the unresectable tumor in patients with bile duct carcinomas (BDC). To achieve effective tumor necrosis, an appropriate approach to laser irradiation is necessary. The efficacy of endoscopy-guided PDT using porfimer (n=12) or talaporfin sodium (n=13) was investigated by evaluating the transhepatic biliary routes and endoscopic retrograde biliary (ERB) routes in 25 patients with BDC. Diseases included perihilar intrahepatic cholangiocarcinoma (ICC) in four patients, extrahepatic BDCs in 19 and ampular carcinoma (AC) in two patients. Adjuvant PDT after surgical resection was performed in 18 patients, and PDT for tumor biliary stenosis was performed in seven. In patients undergoing surgical resections, the mean period between the operation and PDT was 87±42 days. In patients who underwent prior surgical resections, the transhepatic route was used in five (28%), the jejunal loop was used in 11 (61%), the T-tube route was used in one, and the endoscopic retrograde cholangiography (ERC) route via papilla Vater was used in one. In unresectable BDC, the ERC route was used in four patients (57%), and the transhepatic biliary route was used in three (43%). Endoscopic-guided PDT could not be performed in one patient because of a technical failure. Except for the complication of photosensitivity, endoscopy-related complications were not observed in any patients. Patients undergoing PDT with porfimer sodium had a significantly longer admission period compared to patients undergoing PDT with talaporfin sodium (36 vs. 5 days, respectively) (P<0.01). PDT was safely and definitively performed using the endoscopy-guided approach via the transhepatic or ERC route. By considering the disadvantages of both routes, PDT must be adequately achieved for local control of BDC.

Shifting Focus in Optical Image-Guided Cancer Therapy

Cancer patients could benefit from a surgical procedure that helps the surgeon to determine adequate tumor resection margins. Systemic injection of tumor-specific fluorescence agents with subsequent intraoperative optical imaging can guide the surgeon in this process. However, tumor heterogeneity hampers tumor-specific targeting. In addition, determination of adequate resection margins can be very challenging due to invasive tumor strands that are difficult to resolve and because of the confounding effect of variations in tissue optical properties in the surgical margin. We provide an overview of the "classic approach" of imaging tumor-specific targets or tumor-associated pathophysiological processes, and explain the limitations of these targeting strategies. It is proposed that problems of tumor heterogeneity can theoretically be circumvented by shifting focus of tumor targeting towards the follicle-stimulating hormone receptor (FSHR). Furthermore, we discuss why objective determination of resection margins is required to improve resection of the invasive strands, a goal that may be achieved by targeting the FSHR. When invasive strands would nevertheless extend beyond such a standardized resection margin, we suggest that adjuvant photodynamic therapy would be a very suitable therapeutic regimen. Finally, we describe how point optical spectroscopy can be used to scrutinize suspect tissue that is difficult to differentiate from normal tissue by measuring the local tissue optical properties to recover a local intrinsic fluorescence measurement.

Subglottic carcinoma treated with surgery and adjuvant photodynamic therapy

Subglottic cancers are extremely rare as a primary malignancy representing <8% of all laryngeal cancers. Typical age at presentation is in the 5th decade. There are three main types of subglottic carcinoma: adenocarcinoma, mucoepidermoid and adenoid cystic carcinoma. We present a rare case of subglottic cancer treated with surgery and adjuvant photodynamic therapy.

Adjuvant Photodynamic Therapy Does Not Prevent Recurrence of Condylomata Acuminata After Carbon Dioxide Laser Ablation—A Phase III, Prospective, Randomized, Bicentric, Double-Blind Study

Adjuvant Photodynamic Therapy Does Not Prevent Recurrence of Condylomata Acuminata After Carbon Dioxide Laser Ablation—A Phase III, Prospective, Randomized, Bicentric, Double-Blind Study

Subglottic carcinoma effectively treated with surgery and adjuvant photodynamic therapy

Case report A 54-year-old Caucasian male presented to his general medical practitioner in May 2007 with a 2–3 month history of haemoptysis. Radiological examination revealed a radiopacity neck to the right heart border. Panendoscopy showed a pedunculated lesion projecting into the trachea from the cricoid. Excisional biopsy was performed and histopathology showed fragments of a non-cystic epithelial tumour. Further tests showed characteristics of adenocarcinoma.

Adjuvant Photodynamic Therapy Does Not Prevent Recurrence of Condylomata Acuminata After Carbon Dioxide Laser Ablation—A Phase III, Prospective, Randomized, Bicentric, Double-Blind Study

Recurrence after therapy for anogenital warts, or condylomata acuminata (CA), is common. Topical photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) is efficient in the treatment of CA, but one problem with PDT is the limited penetration depth of photosensitizer and light. Pre-PDT vaporization of CA using a carbon dioxide (CO(2)) laser may enhance efficacy. CO(2) laser ablation was followed by ALA-PDT in a phase III prospective randomized bicenter double-blind study to prevent recurrence of CA. One hundred seventy-five patients with CA received CO(2) laser vaporization plus adjuvant ALA-PDT (n=84) or adjuvant placebo-PDT (n=91). A 20% ALA or placebo ointment was applied to the CA area 4 to 6 hours before CO(2) laser vaporization, followed by illumination with red light (600-740 nm, 100 mW/cm(2), 100 J/cm(2)). Cumulative recurrence rate 12 weeks after treatment was 50.0% in the ALA-PDT group, versus 52.7% in the placebo-PDT group (p=.72). No statistically significant difference between groups was detected with regard to recurrence rates up to 12 months after treatment. No major complications were observed. Adjuvant ALA-PDT of CA after CO(2) laser ablation was well tolerated, but no significant difference with regard to recurrence rate was observed from CO(2) laser vaporization alone.