Photodynamic Therapy For Esophageal Cancer Research Articles

The first experience of the application of photodynamic therapy for esophageal cancer in the Astrakhan Regional Clinical Oncologic Dispensary (a case report)

A case report of the application of endoscopic photodynamic therapy in a patient with inoperable squamous-cell cancer of the middle-thoracic part of the esophagus is presented. Two sessions of photodynamic therapy with a 1.5 month interval have been performed. Photosensitizer Photodithazin and a diode laser were used for the treatment. No complications were observed. The treatment resulted in a complete tumor resorption.

Advancements in photodynamic therapy of esophageal cancer.

The poor prognosis of patients with esophageal cancer leads to the constant search for new ways of treatment of this disease. One of the methods used in high-grade dysplasia, superficial invasive carcinoma, and sometimes palliative care is photodynamic therapy (PDT). This method has come a long way from the first experimental studies to registration in the treatment of esophageal cancer and is constantly being improved and refined. This review describes esophageal cancer, current treatment methods, the introduction to PDT, the photosensitizers (PSs) used in esophageal carcinoma PDT, PDT in squamous cell carcinoma (SCC) of the esophagus, and PDT in invasive adenocarcinoma of the esophagus. For this review, research and review articles from PubMed and Web of Science databases were used. The keywords used were "photodynamic therapy in esophageal cancer" in the years 2000-2020. The total number of papers returned was 1,000. After the review was divided into topic blocks and the searched publications were analyzed, 117 articles were selected.

Efficacy and safety of second photodynamic therapy for local failure after salvage photodynamic therapy for esophageal cancer.

Photodynamic therapy (PDT) is an optional salvage treatment for local failure of esophageal squamous cell carcinoma (ESCC) after chemoradiotherapy; however, local failure after PDT sometimes occurs. In such cases, second PDT is sometimes attempted, but its outcomes remain unclear. This study aimed to evaluate the efficacy and safety of second PDT. We enrolled patients who underwent PDT for local failure of ESCC after chemoradiotherapy. We retrospectively evaluated local-complete response (L-CR) rate and clinical outcomes of first and second PDT. The indications for PDT were lesions within the muscle layer, <3 cm in size, and <3/4 of the esophageal circumference; not suitable for salvage surgery; and absence of metastasis. Second PDT was avoided when lesions were apparently refractory to first PDT, e.g. persistence of submucosal tumor-like protruded component or rapid regrowth of tumor at the ulceration after first PDT. L-CR was defined as endoscopic disappearance of tumor and post-PDT ulcer and absence of cancer cells histologically. Among 82 patients who underwent first PDT, 27 underwent second PDT. The L-CR rates with first and second PDT were 63.0% and 40.7%, respectively. The 2-year overall survival rates after second PDT in patients with L-CR and local-nonCR were 79.5% and 40.5%, respectively. Five of 11 patients with L-CR survived without any recurrence. No grade ≥3 adverse events occurred. Second PDT demonstrated excellent safety and acceptable efficacy; therefore, it could be a useful treatment for local failure after first PDT.

Repeated talaporfin sodium photodynamic therapy for esophageal cancer: safety and efficacy

BackgroundTalaporfin sodium photodynamic therapy (tPDT) is an effective salvage treatment for local failure after chemoradiotherapy for esophageal cancer. Repeated tPDT could also be indicated for local recurrence or residue after the first salvage tPDT. However, the safety and efficacy of repeated tPDT have not been elucidated.MethodsWe reviewed 52 patients with esophageal cancer who were treated with the first tPDT at Kyoto University Hospital between October 2015 and April 2020.ResultsAmong 52 patients, repeated tPDT after the first tPDT was indicated for 13 patients (25%), of which six had residual tumor, four had local recurrence after complete response (CR) after the first tPDT at the primary site, and six had metachronous lesion. The total session of repeated tPDT was 25; 16 were for primary sites and nine were for metachronous sites. Among them, six patients (46.2%) achieved local (L)-CR and nine lesions (56.3%) achieved lesion L-CR. By session, 10 sessions (40%) achieved L-CR. There were no severe adverse events except for one patient; this patient showed grade 3 esophageal stenosis and perforation after the third tPDT on the same lesion that was previously treated with porfimer sodium photodynamic therapy four times.ConclusionRepeated tPDT could be an effective and safe treatment for local failure even after salvage tPDT for esophageal cancer.

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Oxygen saturation imaging as a useful tool for visualizing the mode of action of photodynamic therapy for esophageal cancer.

Background and aimsOxygen saturation (OS) imaging is a novel technique that directly measures and visualizes the tissue oxygen saturation at the surface of the GI tract. Our purpose was to evaluate the ability of OS imaging to visualize the action mode of photodynamic therapy (PDT).MethodsEight patients with local recurrence after chemoradiotherapy for esophageal cancer were enrolled. OS imaging observation was performed before PDT, after 100 J/cm2 illumination and illumination completion, and on the second day.ResultsOS imaging showed an extreme change in the hypoxic state in the illuminated area, although the change was near invisible on white-light imaging. The median tissue oxygen saturation value at the tumor lesion was 61.5% (range, 36%-91%) before PDT and significantly decreased immediately after illumination: 11% (range, 0%-57%) after 100 J/cm2 illumination, 1% (range, 0%-6%) at PDT completion, and 2% (range, 0%-12%) on the second day.ConclusionsOS imaging could be a useful tool to visualize changes after PDT.

Photodynamic Therapy for Esophageal Cancer.

Photodynamic therapy, a curative local treatment for esophageal squamous cell carcinoma, involves a photosensitizing drug (photosensitizer) with affinity for tumors and a photodynamic reaction triggered by laser light. Previously, photodynamic therapy was used to treat superficial esophageal squamous cell carcinoma judged to be difficult to undergo endoscopic resection. Recently, photodynamic therapy has mainly been performed for local failure after chemoradiotherapy. Although surgery is the most promising treatment for local failure after chemoradiotherapy, its morbidity and mortality rates are high. Endoscopic resection is feasible for local failure after chemoradiotherapy but requires advanced skills, and its indication is limited to within the submucosal layer by depth. Photodynamic therapy is less invasive than surgery and has a wider indication than endoscopic resection. Porfimer sodium (a first-generation photosensitizer) causes a high frequency of side effects related to photosensitivity and requires the long-term sunshade period. Talaporfin (a second-generation photosensitizer) requires a much shorter sun-shade period than porfimer sodium. Photodynamic therapy will profoundly change treatment strategies for local failure after chemoradiotherapy.

Usefulness of Repeated Photodynamic Therapy for Local Recurrence After Photodynamic Therapy for Esophageal Cancer

Usefulness of Repeated Photodynamic Therapy for Local Recurrence After Photodynamic Therapy for Esophageal Cancer

Photodynamic therapy for esophageal cancer.

Photodynamic therapy (PDT) is a treatment that uses a photosensitizing drug that is administered to the patient, localized to a tumor, and then activated with a laser to induce a photochemical reaction to destroy the cell. PDT using porfimer sodium followed by excimer dye laser irradiation is approved as a curative treatment for superficial esophageal cancer in Japan. While endoscopic submucosal dissection (ESD) is currently more popular for esophageal cancer, there is evidence to support PDT as an alternative treatment and as a salvage treatment for local failure after chemoradiotherapy (CRT). A photosensitizing agent has also been developed that requires a shorter sun shade period after administration, and studies are currently underway to establish an esophageal cancer indication for this next-generation PDT in Japan.

Where Does Photodynamic Therapy Fit in the Esophageal Cancer Treatment Jigsaw Puzzle?

Traditional treatment options for esophageal cancer have centered on the triad of surgery, chemotherapy, and radiotherapy. Although surgery remains the gold standard for operable disease, photodynamic therapy (PDT) is emerging as a valid minimally invasive option for select patients with inoperable disease. Years of experience with PDT for esophageal cancer seem to suggest that it may be particularly useful for treatment of early unresectable lesions, palliation of locally advanced disease, and salvage therapy for stent blockage or local tumor recurrence. Further investigation into the ideal role for PDT, perhaps through a comparative study with other nonsurgical options, may help clarify where it fits in the treatment armamentarium for esophageal cancer.

Photodynamic Therapy for Urological Malignancies: Past to Current Approaches

Modern PDT for urological tumors is a potentially selective approach in which in situ photosensitization by a nontoxic drug, locally activated by light, generates cytotoxic reactive oxygen species, causing cell death. While urological clinical experience with PDT is largely limited to treatment for superficial bladder cancer, the advent of novel photosensitizers and technologies for treatment planning, light delivery and dosimetry, PDT for prostate and other urological cancers appears increasingly realistic. We reviewed the current literature on PDT for urological tumors, in addition to recent emerging data from our laboratory and elsewhere. Remarkable progress has been made in the field of photochemistry and photobiology. Together with improved optical delivery and imaging systems PDT holds promise as an alternative, minimally invasive and potentially curative treatment for localized solid tumors as well as for palliative treatment for isolated, clinically problematic metastases. Current experience with photodynamic therapy using contemporary photosensitizing agents and light sources is mainly restricted to in vivo experimental models and early phase clinical trails. However, ongoing preclinical work and clinical trials indicate that safer and effective PDT treatments in uro-oncology are imminent.

Photodynamic therapy (PDT) in esophageal cancer: a surgical view of its indications based on 14 years experience.

The aim of this paper is to present the updated experience of the Yorkshire Laser Centre in PDT for esophageal cancer and to identify its role in specific subsets of patients. Also, in the light of this experience, to compare and contrast the results of PDT with appropriate subsets of patients treated in my esophageal surgery practice. 102 consecutive patients; 84 with advanced (Group A) and 18 with early (Group E) stage esophageal cancer undergoing endoscopic PDT were entered into a prospective study. Every patient had standard work up including clinical staging. PDT protocol was intravenous administration of Photofrin 2mg/kg body weight followed 24-72 hours later by endoscopic illumination using 630 nm laser light. Assessment of results was made on the basis of mortality, morbidity, patient satisfaction to treatment, symptom relief and survival. For comparison of PDT role with non PDT treated patients, reference is made to 3 previous publications comprising over 1100 patients [Moghissi, K., Br. J. Surg. 79, 935-937 (1992) (ref. 1); Sawant, D., Moghissi, K. Eur. J. Cardio-Thorac. Surg. 8, 113-117 (1994) (ref. 2); Sharpe, D. A. C., Moghissi, K. Eur. J. Cardiothorac. Surg. 10, 359-364 (1996) (ref. 3)]. There was no mortality associated with PDT. All patients expressed satisfaction to treatment. Post PDT complications consisted of photosensitivity skin reaction (sunburn) in 5 patients (5%) and esophageal stricture in 8 (8%) patients. Group A: There was significant symptom and dysphagia grade improvement. Mean survival was 9.5 months. Group E: There were no significant symptoms pre or post PDT and mean survival was 60.5 months. Comparison of PDT results in Group A with results of other palliative treatment methods, indicates that palliation can be achieved in all intraluminal cancer using PDT which is at least as good as other treatments. There is, in addition, advantage over other methods in patients with cervical esophageal cancer and in cases with re-growth of tumor obstructing previously placed stents. In early cases PDT appears capable of replicating surgical results in selected cases. PDT is an effective and safe treatment method in esophageal cancer. In advance disease it improves swallowing. In early stage disease it offers long survival and the prospect of cure in some patients. At present the role of PDT in early stage cancer should be limited to patients who are unsuitable for surgical resection. Therefore, PDT should be considered as a valid oncological option to be applied in selected cases.

Photodynamic therapy for esophageal cancer: a useful and realistic option.

The use of light therapy for tissue destruction is highly attractive for the endoscopic and minimally invasive therapy of esophageal cancer. Photodynamic therapy (PDT) offers the possibility of palliation of advanced obstructing tumors. However, there are other competing techniques, which can be used to open the esophageal lumen. It has also proved very effective in providing prolonged palliation of patients with advanced irresectable cancer. Completely obstructing tumors, tortuous and long lesions, and tumors near the upper end of the esophagus are particularly suitable for photodynamic therapy. Patients with obstruction to an esophageal prosthesis are also well palliated with PDT. A more interesting and exciting development is its use for the eradication of early asymptomatic mucosal disease. Photodynamic therapy is particularly useful for the eradication of field cancerous change in patients with pre-malignant Barrett's esophagus, or early tumors in patients unfit for radical therapy.

Balloon photodynamic therapy of esophageal cancer: effect of increasing balloon size.

Photodynamic therapy is currently being used to treat various malignancies including esophageal cancer. The effect of photodynamic therapy depends upon the concentration of photosensitizing drug, light energy delivered to tissue, and the presence of oxygen in the targeted tissue. We have found that an esophageal centering balloon improves light delivery to esophageal mucosa. However, balloon pressure on esophageal mucosa could possibly reduce mucosal blood flow and oxygenation, therefore reducing the effect of photodynamic therapy. This study was conducted to investigate the effect of balloon pressure on the esophageal wall during photodynamic therapy in the canine esophageal model. Studies were performed in the canine esophagus of ten animals to investigate whether increasing the size of the centering balloon, and hence the pressure on esophageal mucosa, would alter the tissue effect of PDT. Porfimer sodium 4 mg/Kg was administered and 630 nm light was delivered via a 1 cm diffuser located in the center of a 360 degrees 2 cm windowed balloon. Mucosal light measurements were made to ascertain equivalent mucosal light dosing of approximately 25 J/cm2. Endoscopic and necropsy findings obtained following photodynamic therapy with 25 mm, 33 mm, and 35 mm balloons were compared. In larger dogs (groups A and B), increasing the size of the esophageal centering balloon from a 25-33 mm size did not result in an overly tight fit nor was the increase associated with significant change in the PDT effect. In contrast, increasing the balloon size to 35 mm in smaller dogs (group C) resulted in a tight fit of the balloon in the esophagus and in significant reduction in the PDT effect on mucosal damage when mucosal equivalent light dose was administered during photodynamic therapy in the canine esophageal model. Increasing centering balloon size resulted in reduced tissue damage when mucosal equivalent light dose was administered during photodynamic therapy in the canine esophageal model. Proper sizing of centering balloons will be necessary for balloon PDT of esophageal mucosal dysplasia or cancer in humans.

Long-term survival after photodynamic therapy for esophageal cancer

Background/Aims: Photodynamic therapy (PDT) has been adapted to the endoscopic treatment of digestive cancer, but its indications and efficacy remain uncertain. The aim of this study was to assess its feasibility in the curative treatment of small esophageal tumors. Methods: From 1983 to 1991, PDT was used to treat 123 patients with esophageal cancer who were recommended for nonsurgical treatment of squamous cell carcinoma (n = 104) and adenocarcinoma (n = 19). Endoscopic ultrasonography (EUS) was performed in 88 patients; 61 were staged uT1 and 27 were staged uT2. A hematoporphyrin derivative was injected 72 hours before laser irradiation with a 630-nm dye laser. PDT was applied alone in 56 patients and as part of a multimodal protocol in the 67 others. Results: The complete response rate at 6 months was 87%. The 5-year survival rate was 25% ± 6%, and the 5-year disease-specific survival rate was 74% ± 5%. The complete response rate and survival rate were not different (1) between the PDT alone and the PDT multimodal treatment groups, (2) between the adenocarcinoma and squamous cell carcinoma groups, and (3) between the uT1 and uT2 EUS groups. PDT-related complications were esophageal stenosis (n = 43) and cutaneous photosensitization (n = 16). Conclusions: In patients with small esophageal tumors who pose high surgical risk, photodynamic therapy is an effective treatment.

食道癌のPDT、側視鏡を用いる方法

Esophageal cancer reacts to photodynamic therapy (PDT) markedly and it necrotizes easily besides the ulcer after PDT repairs soon, because it is more sensitive to PDT than gastric cancer. In order to improve the therapeutic effectiveness of PDT with Photofrin II and laser light for superficial esophageal cancer, we employed an excimer dye laser instead of an argon dye laser since 1990. The characteristics of the current laser are as follows: wavelength, 630nm; pulse energy, 4mJ; peak power, 400kW; pulse width, 10nsec; frequency of repetition, 80Hz; average output, 320mW. The entire lesion plus a 5-mm wide perimeter of mucosa was irradiated with an EDL beam at 630nm wave length transmitted endoscopically.In PDT for esophageal cancer, we had used a front-view fiberscope (model GIF-P10, GIF-XQ20, Olympus, Tokyo, Japan) for five cases with esophageal cancer according to the traditional method of diagnostic endoscopy until 1991. But uniform irradiation was difficult, especially with large lesions, because of esophageal peristalsis and respiratory movement. Since the first trial using a side-view fiberscope in PDT for esophageal cancer in 1992, we used a side-view fiberscope (model GF-20, Olympus, Tokyo, Japan) for five cases with esophageal cancer, not only in PDT, but also in pretreatment examinations and follow-up examinations. Two of them were located in abdominal esophagus (Ea) just above EC junction, where PDT had been considered out of application. In this procedure, patients with a lesion located on the right side can lie in a left lateral position as usual, whereas patients with a lesion located in the left side, especially from 7 to 10 o'clock, must lie in a right lateral position. This enabled photoradiation of esophageal cancer from a 90°angle without any difficulty, besides with less energy intensity of the irradiated laser light. Of these 10 lesions, 9 were cured by initial treatment and no recurrence was proved by endoscopy and biopsy. The final rate of cure was 90% (9/10).

Photodynamic therapy for esophageal cancer using a 180 degrees windowed esophageal balloon.

Although delivery of uniform circumferential light is desirable during photodynamic therapy of advanced esophageal cancer in humans, early esophageal cancer may need only targeted treatment. Studies were performed in the canine esophagus of eight animals to investigate whether use of a "windowed" (shaded) centering balloon would improve targeted illumination of esophageal mucosa for photodynamic therapy. Shaded balloons were developed with a 2-cm-long, 360 degrees or 180 degrees clear "window." Photofrin 4 mg/Kg was used as the photosensitizer. Light at 630 nm was delivered at 300 J/cm or 600 J/cm. Isotropic probes placed on the balloon wall allowed real-time measurement and verification of relatively uniform light doses delivered to esophageal mucosa during balloon photodynamic therapy. With the windowed balloon, targeted delivery of photodynamic therapy was possible. Using the 180 degrees balloon, mucosa exposed to illumination was destroyed, whereas mucosa protected from light by the balloon shading was undamaged. Healing was complete and strictures did not occur. The shading of the balloon protected normal mucosa and prevents the formation of esophageal strictures. The "windowed" centering balloon provides a technology and technique that allows targeted delivery of uniform light during esophageal PDT.

A centering balloon for photodynamic therapy of esophageal cancer tested in a canine model

Delivery of uniform circumferential light is desirable during photodynamic therapy of early or advanced esophageal cancer in human beings. Studies were performed in the canine esophagus to investigate whether use of a centering balloon would improve circumferential illumination of esophageal mucosa for photodynamic therapy of esophageal cancer. When the centering balloon was used, photodynamic therapy produced uniform and circumferential injury. With the cylindrical diffuser used in human studies, non-uniform and focal esophageal injury occurred. Placement of isotropic probes on the balloon wall allowed measurement and verification of relatively uniform light doses delivered to esophageal mucosa during balloon photodynamic therapy. The centering balloon has a potential role in improving light dosimetry during esophageal photodynamic therapy.

Laser and photodynamic therapy of esophageal cancer.

With proper selection of patients with non-operative esophageal cancer, palliative therapy with Nd:YAG laser enhances the quality of life by improving the patient's ability to swallow soft or solid food. Also, the use of non-thermal laser light to initiate the process of photodynamic therapy (PDT) is an additional laser technique that appears effective, not just in palliative treatment, but also in the cure of early esophageal cancer. For PDT, considerable work will be necessary to provide standard techniques in tumor staging, light and drug delivery and in light dosimetry. Ultimately, palliative and curative therapy of esophageal cancer will most likely incorporate multiple modalities, including surgery, radiation, chemotherapy, stents, laser and other thermal modalities, photodynamic therapy, and combinations of these methods.

Photodynamic Therapy for Esophageal cancer

In photodynamic therapy, a photosensitizing drug is injected and then activated by light in the red spectral region to produce reactive, highly toxic singlet oxygen, which causes cell tissue and damage. When the distinction between tumoral and normal tissue is difficult at endoscopy, photodynamic therapy is preferable to any other conservative method of destruction. The main indications comprise genital, head and neck, bronchial, bladder and gastrointestinal tumours, particularly esophageal cancer (including squamous cell cancer and glandular neoplasia). Esophageal tumours should be class T1 or T2, at most, and detected at endoscopy. Dysplasia which is flat, sessile and multicentric may also be an indication for photodynamic therapy. Advanced esophageal cancers are contraindicated for photodynamic therapy.