Oxygen plays a major role in cancer biology and tumor progression. In PDT, the reduction in efficacy is directly related
to lack of oxygen because its molecular mechanism relies on oxygen as an energy mediator. Measuring tumor
oxygenation can provide physicians with better diagnosis and optimization of treatment plans. However, clinical tools
for directly assessing tissue oxygenation are limited. The gold standard is oxygen needle electrode, which is invasive and
measures oxygen level at a single location.
We present our work on developing a combined treatment-imaging modality that integrates PDT and photoacoustic
oxygen imaging. We propose a system designed for clinical treatments of cancer of the oral cavity. Tissue oxygen
imaging is performed by applying Photoacoustic Lifetime Imaging (PALI). This technology relies on photoacoustic
probing of oxygen-dependent excitation lifetime of Methylene Blue. The dye is excited by the same wavelength of
illumination source for PDT. Once excited, the population of photosensitizer molecules at triplet state has a lifetime
depending on the oxygen level. The transition from excited triplet state to ground state can be probe by another laser,
which generate photoacoustic signal that is used to map the lifetime. The lifetime map is then converted to pO2
distribution.
We expect that PDT efficacy can be improved by applying PALI imaging feedback in real-time to determine, and
individually optimize, O2-enriched gas breathing parameters and PDT light-dose during treatment. Successful
implementation of PALI in PDT can also drive its application in guiding other cancer treatments that are affected by
hypoxia.
One hundred thirty patients with neoplastic diseases of the larynx, oral cavity, pharynx and skin have been treated with photodynamic therapy (PDT) with follow-up to 79 months. Those patients with primary or recurrent leukoplakia, carcinoma-in- situ (CIS) and T1 carcinomas obtained a complete response after one PDT treatment and 87% remain free of disease. Sixteen patients with deeply invasive T2 and T3 carcinomas were treated with PDT. Of those sixteen, ten obtained a complete response, but six have recurred locally. Although a response can be achieved with PDT in the larger solid tumors, it is not a consistent complete response because of the depth of invasion of the tumor. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. Fourteen patients with massive recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Two patients developed a local recurrence within the field of treatment. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. T2 and T3 superficial carcinomas, with invasion less than 0.5 cm, are also curatively treated with PDT with significantly reduced morbidity compared to conventional modes of treatment. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.
Seventy-nine patients with neoplastic diseases of the larynx, oral cavity, pharynx, and skin have been treated with photodynamic therapy (PDT) with follow-up to 65 months. Patients with carcinoma-in-situ (CIS) and T1 carcinomas obtained a complete response after one PDT treatment. All but two patients remain free of disease. Four patients with T2 and T3 superficial carcinomas were treated with PDT. One patient developed recurrence with 51- month follow-up. Eleven patients with deeply invasive T2, T3, and T4 carcinomas were treated with PDT. Of those eleven, eight obtained a complete response, but five have recurred locally. A response can be achieved with PDT, although not a consistent complete response because of the depth of invasion of the tumor. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. Eight patients with massive neck recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Only one patient developed recurrence with 30-month follow-up. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. T2 and T3 superficial carcinomas, with invasion less than 0.5 cm, are also curatively treated with PDT with significantly reduced morbidity compared to conventional modes of treatment. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.
Despite aggressive surgical and radiotherapy, recurrence rates for patients with recurrent head and neck carcinomas remain high. Photodynamic therapy has been successfully used to treat patients with early carcinomas. This is due to the ability of the activating laser light to penetrate up to one centimeter into tissue, resulting in destruction of microscopic tumor with preservation of normal tissues. Employing this principle, PDT was used as an adjuvant intraoperative therapy following resection of tumor in five patients with recurrent infiltrating carcinomas of the head and neck. All patients tolerated the treatment without complications and all but one remains free of disease twenty-four months post-treatment. Adjuvant intraoperative PDT may improve cure rates of recurrent head and neck malignancies by providing for larger tumor-free margins of resection while preserving normal structures.
Photodynamic therapy (PDT) is an innovative treatment involving the use of light-sensitive drugs to selectively identify and destroy diseased cells. Therefore, photodynamic therapy has the potential to treat and cure precancerous and early cancerous lesions (carcinoma in situ (CIS), T1 and T2) of the larynx while preserving normal tissue. Twenty-four patients with recurrent leukoplakia and carcinomas of the larynx were treated with PDT with follow-up to 60 months. Fourteen patients with T1 squamous cell carcinomas of the vocal cord, 2 patients with a T2 squamous cell carcinoma of the vocal cord failing radiotherapy, and 6 patients with CIS and sever atypia were treated with PDT and obtained a complete response and are disease free. One patient with a T3 carcinoma of the larynx was treated with PDT but died 5 weeks post-treatment of unrelated causes and could not be assessed. Photodynamic therapy is a promising therapy for treatment of precancerous and cancerous lesions of the larynx. This therapy may be particularly beneficial for the treatment of recurrent carcinomas of the larynx that have failed conventional radiotherapy, thereby preserving voice and eliminating the need for destructive laryngeal surgery.
Sixty-five patients with neoplastic diseases of the larynx, oral cavity, pharynx, and skin have been treated with PDT with followup to 56 months. Patients with carcinoma in situ and T1 carcinomas obtained a complete response after one PDT treatment. All but two have remained free of disease. Eight patients with T2 and T3 carcinomas treated with PDT obtained a complete response, but they all recurred locally. This is due to the inability to adequately deliver laser light to the depths of the tumor bed. five patients with massive neck recurrences of squamous cell carcinomas were treated with intraoperative adjuvant PDT following tumor resection. Only one developed recurrence with 24- month followup. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. Also, intraoperative adjuvant PDT may increase cure rates of large infiltrating carcinomas of the head and neck.
Photodynamic therapy (PDT) has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Fifty-three patients with neoplasia of the head and neck have been treated with PDT with follow-up to 40 months. Eight patients with T2-T4 carcinomas of the upper aerodigestive tract had a partial response. Eighteen patients with CIS and T1 carcinomas of the larynx obtained a complete response and are disease free. Eleven patients with T1 carcinomas of the tongue, floor of mouth, and nasal cavity obtained a complete response. Three patients with mucosal melanomas of the nasopharynx obtained a complete response and remain disease free. Two patients with Kaposi's sarcoma or the oral cavity were treated, one obtained a complete response. Five patients with juvenile laryngotracheobronchial papillomatosis obtained a complete response, but all recurred within six months of treatment. PDT is a promising therapy for treatment of early neoplasia of the head and neck. There are, however limitations to this treatment based on tumor size and site. Methodology, clinical response, limitations and complications are discussed.
Despite aggressive surgical and radiotherapy, recurrence rates for patients with recurrent head and neck carcinomas remain high. Photodynamic therapy has been successfully used to treat patients with early carcinomas. This is due to the ability of the activating laser light to penetrate up to one centimeter into tissue resulting in destruction of microscopic tumor with preservation of normal tissues. Employing this principle, PDT was used as an adjuvant intraoperative therapy following resection of tumor in four patients with recurrent infiltrating carcinomas of the head and neck. All patients tolerated the treatment without complications and remain free of disease six months post-treatment. Adjuvant intraoperative PDT may improve cure rates of recurrent head and neck malignancies by providing for larger tumor-free margins of resection while preserving normal structures.
Forty-nine patients with neoplastic diseases of the larynx, oral cavity, pharynx and tracheobronchial tree have been treated with photodynamic therapy with follow-up to 40 months. Those patients with primary recurrent leukoplakia, carcinoma-in-situ, and T1 carcinomas obtained a complete response after one photodynamic therapy (PDT) treatment and remain free of disease. Eight patients with T2 and T3 carcinomas treated with PDT obtained a complete or partial response, but in all cases, the carcinomas recurred locally, many times with overlying normal mucosa. This is due to the inability to adequately deliver laser light to the depths of the tumor bed, despite aggressive use of interstitial implantation. PDT is highly effective for the curative treatment of early carcinomas (CIS, T1) of the head and neck. Further development of devices to measure and deliver light into the depths of a tumor bed are required prior to the use of PDT to effectively treat larger solid tumors of the head and neck.
Photodynamic therapy has the potential to treat and cure early carcinomas of the head and neck while preserving normal tissue. Thirty patients with neoplasia of the head and neck have been treated with PDT with follow-up to twenty nine months. Four patients with T3 and T4 carcinomas of the upper aerodigestive tract had a partial response. Eleven patients with T1 and T2 carcinomas of the larynx obtained a complete response and are disease free. Seven patients with T1 carcinomas of the tongue, floor of mouth, and nasal cavity obtained a complete response. Three patients with mucosal melanomas of the nasopharynx obtained a complete response and have remained disease free. Two patients with Kaposi's sarcoma of the oral cavity were treated. One obtained a complete response. Three patients with recurrent juvenile laryngotracheal papillomatosis obtained a complete response, but one recurred four months post-PDT. PDT is a promising therapy for treatment of early neoplasia of the head and neck. There are, however, limitations to this treatment based on tumor size and site. Methodology, clinical response, limitations, and complications will be discussed.
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