In case of obstructive tumors, when symptoms recur within 30 days after the rst treatment or if additional bronchoscopy reveals local recurrence, patients could receive a second PDT session. The same dose of photosensitizer followed by laser photoradiation can be repeated. Patients could receive a maximum of three photosensitizers doses at 1-month intervals and up to 6 laser photo-irradiations, with a maximum of 2 photo-­ irradiations per session. If toxic effects occur, treatment must be withheld until they resolve.

Indications

Summary of curative and palliative indications of photodynamic therapy in the management of patients with non-small cell carcinoma is depicted below [45–47] (Table 14.2).

Curative PDT Indications

\1.\ In situ Carcinoma ( rst-line indication)

\2.\ Microinvasive and limited to the bronchial wall non-small cell lung cancer:

\ (a)\ Early-stage intraluminal and central tumors following de nitive surgery or radiation therapy

\(c)\ Synchronous primary carcinomas

\3.\ Recurrence of operated non-small cell lung carcinoma (stump area) or treated by radiotherapy

4. Severe dysplasia

Patient’s selection should be cautious taking into account area and depth of tumoral extent. The Japanese Lung Cancer Society in 2010 de ned the criteria of early central lung tumor selection [48]:

––distal limit at subsegmental bronchus location,

––bronchoscopically identi ably tumor margins,

––tumor size less than 2 cm in its greatest dimension, and

––squamous cell carcinoma is proven histologically. 1

––It also de nes three types of lesions according to the endoscopic appearance: fat lesions, nodular lesions, and early polypoid lesions. It has been shown that lesions protruding (nodular or polypoid) tend to invade the bronchial wall deeper than the fat-type lesions. Flat lesions <1 mm in diameter and visible distal margins are in situ carcinoma more than 90%

of the time, suggesting this to be the ideal indication [49, 50].

Palliative PDT Indications

\1.\ Endobronchial obstruction caused by any type of tumor: all histological types, primary and/or metastatic, have responded to treatment [51–53].

Small cell carcinoma is not included among the histologic types that can bene t from this treatment mainly because it is known that these tumors respond well to chemotherapy and because they present more as in ltrative tumors than obstructive masses.

\2.\ Slow down tumor progression.

\3.\ Improve symptoms such as bleeding, secretions, and dyspnea [51, 54].

\4.\ Some authors have suggested to use PDT for inoperable patients making them candidates for surgical treatment [55–57].

Review of available data on this indication, published by four authors [58–61] shows results of 106 responses on 111 patients treated.

Recently, PDT has been used at the Tokyo Medical University Hospital as pre-operative therapy in 26 patients, reducing the extension of non-small cell tumor and/or converting patients into operable candidates. Four of the 5 patients originally inoperable became operable, and 18 of the 21 patients originally can-

didates for pneumonectomy were eligible for less invasive surgery such as lobectomy [57].

\5.\ Recurrence at the surgical stump. Historically, survival of these patients is around 9 months. McCaughan and Williams have observed 5-year survivals of similar cases treated repeatedly with PDT [54].

\6.\ Bleeding control, through PDT ability to cause thrombosis of small vessels. In a study, the amount of bleeding was recorded before, during, and after treatment with PDT, and there was statistically a signi - cant reduction of bleeding during and after PDT treatment. PDT has also been described as effective in the palliative treatment of patients with uncontrollable life-threaten- ing hemoptysis [62].

\7.\ Malignant pleural dissemination: patients can be treated by PDT following a complete surgical resection. As with malignant pleural mesothelioma, PDT may be utilized as part of multimodality management. In fact, PDT can be used for non-small cell lung cancer with pleural spread. In a phase II trial with pleural spread and clinical T4 non-small cell lung cancer, 20 patients underwent surgery that was followed by pleural PDT, and in only 2 patients, PDT was practiced alone. After 6 months of control, the rate of survival was 73.3%, and median overall survival was 21.7 months, compared with 6–9 months for similar patients based on historical controls [63].

See Table 14.3.