Feasibility Study of Using Navigational Bronchoscopy to Perform PDT-Photofrin® in Unresectable Peripheral Lung Cancer

Number of times photodynamic therapy was delivered into the tumor using navigational bronchoscopy for each subject.

The incidence of adverse events following navigational bronchoscopy-iPDT (interstitial-Photodynamic Therapy) will be presented as the primary safety indicator for this treatment.

From the start of treatment until 3 months post-treatment measured as per the Modified RECIST (Response Evaluation Criteria in Solid Tumors) Criteria

From the start of treatment until 6 months post-treatment measured as per the Modified RECIST (Response Evaluation Criteria in Solid Tumors) Criteria

Measured at screening to be the baseline measure. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.

Measured at Day 1 which is day of the photofrin injection. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.

Measured at Day 3. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.

Measured at Day 3. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.

Measured at 3 months. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.

Measured at 6 months. The Eastern Cooperative Oncology Group (ECOG) scores range from 0 to 5. The lowest values mean a better outcome: 0 is fully active with no performance restrictions; 1 is strenuous physical activity restricted but fully ambulatory and able to carry out light work; 2 is capable of all self-care but unable to carry out any work activities - up and about >50% of waking hours; 3 is capable of only limited self-care and confined to bed or chair >50% of waking hours; and 4 is completely disable, cannot carry out any self-care and totally confined to bed or chair.

The Short-Form Health Survey (SF-36) scores range from 0 to 100, with higher scores indicating better health status. SF-36 evaluates 9 dimensions of Health: physical function, role limitations due to physical health problems, body pain, general health, vitality, social functioning, role limitations due to emotional problems domain, and mental health. Summary is provided in the form of physical component score (PCS) and mental component score (MCS) for each of the timepoints.

The Short-Form Health Survey (SF-36) scores range from 0 to 100, with higher scores indicating better health status. SF-36 evaluates 9 dimensions of Health: physical function, role limitations due to physical health problems, body pain, general health, vitality, social functioning, role limitations due to emotional problems domain, and mental health. Summary is provided in the form of physical component score (PCS) and mental component score (MCS) for each of the timepoints.

The Short-Form Health Survey (SF-36) scores range from 0 to 100, with higher scores indicating better health status. SF-36 evaluates 9 dimensions of Health: physical function, role limitations due to physical health problems, body pain, general health, vitality, social functioning, role limitations due to emotional problems domain, and mental health. Summary is provided in the form of physical component score (PCS) and mental component score (MCS) for each of the timepoints.

Baseline score of EORTC QLQ-C30 which is a multi-dimensional Health Related Quality of Life measure designed for use in lung cancer patients. Includes 5 functional measures (physical, role, emotional, social, cognitive), 8 symptoms (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea) and global health status and financial impact. Most items use 4-item scale from "not at all" to "very much". Raw scores are transformed to 0-100 scale with higher scores representing better functioning/Quality of Life and greater symptom burden.

3 month score of EORTC QLQ-C30 which is a multi-dimensional Health Related Quality of Life measure designed for use in lung cancer patients. Includes 5 functional measures (physical, role, emotional, social, cognitive), 8 symptoms (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea) and global health status and financial impact. Most items use 4-item scale from "not at all" to "very much". Raw scores are transformed to 0-100 scale with higher scores representing better functioning/Quality of Life and greater symptom burden.

6 month score of EORTC QLQ-C30 which is a multi-dimensional Health Related Quality of Life measure designed for use in lung cancer patients. Includes 5 functional measures (physical, role, emotional, social, cognitive), 8 symptoms (fatigue, pain, nausea/vomiting, appetite loss, constipation, diarrhea, insomnia, dyspnea) and global health status and financial impact. Most items use 4-item scale from "not at all" to "very much". Raw scores are transformed to 0-100 scale with higher scores representing better functioning/Quality of Life and greater symptom burden.

Baseline measure for EORTC QLQ-LC13 which is a 13-item lung cancer-specific questionnaire module. It is used in conjunction with the QLQ-C30. It is comprised of multi-item and single-item measures of lung cancer associated symptoms (coughing, hemoptysis, dyspnea, pain) and side effects from conventional chem-and radiotherapy (alopecia, neuropathy, sore mouth, dysphagia). For these symptom-oriented scales, a higher score means more severe symptoms. The scale is from 1 (not at all) to 4 (very much). The scoring (as reported here) is from 0 to 100 with the higher score meaning a more severe symptom.

3-Month measure for EORTC QLQ-LC13 which is a 13-item lung cancer-specific questionnaire module. It is used in conjunction with the QLQ-C30. It is comprised of multi-item and single-item measures of lung cancer associated symptoms (coughing, hemoptysis, dyspnea, pain) and side effects from conventional chem-and radiotherapy (alopecia, neuropathy, sore mouth, dysphagia). For these symptom-oriented scales, a higher score means more severe symptoms. The scale is from 1 (not at all) to 4 (very much). The scoring (as reported here) is from 0 to 100 with the higher score meaning a more severe symptom.

6-Month measure for EORTC QLQ-LC13 which is a 13-item lung cancer-specific questionnaire module. It is used in conjunction with the QLQ-C30. It is comprised of multi-item and single-item measures of lung cancer associated symptoms (coughing, hemoptysis, dyspnea, pain) and side effects from conventional chem-and radiotherapy (alopecia, neuropathy, sore mouth, dysphagia). For these symptom-oriented scales, a higher score means more severe symptoms. The scale is from 1 (not at all) to 4 (very much). The scoring (as reported here) is from 0 to 100 with the higher score meaning a more severe symptom.

Adverse events (AEs) noted by number of participants with at least one event. An AE was defined as any untoward medical occurrence in a subject during the course of the study, regardless of causal relationship. AEs were coded using MedDRA Version 21.1

The number of subjects with at least one serious adverse event are listed.

Safety evaluation will include the physical examinations summary of non-normal findings for each subject.

Safety evaluation included vital sign summary for each subject. Vital signs included pulse, blood pressure, temperature and respiration rate. Only clinically relevant results, as per the investigator judgement, are included. These would be vital signs that are out of the normal range but could be considered outside enough to be clinically relevant to the subject's health.

The treatment emergent adverse events related to PFTs are noted. Pulmonary function test measurements were: Diffusion Capacity of Lung for Carbon Monoxide (%), Expiratory Reserve Volume (mL), Forced Vital Capacity (mL), Forced Expiratory Volume in 1 second (mL), Forced Expiratory Flow 25% to 75% (L/min), Functional Residual Capacity (mL), Maximum Voluntary Ventilation (L/min), Residual Volume (mL), Peak Expiratory Flow (L/min), Slow Vital Capacity (mL), Total Lung Capacity (mL)

Safety evaluation includes laboratory tests summarized for each subject with any abnormal lab results considered an Adverse Event to be listed. The investigators commented on any laboratory value outside the normal reference range. If the value was judged to be an Adverse Event, it is listed. The values analysed were: Hematology (Hemoglobin, Hematocrit, White Blood Cell, Red Blood Cell, Platelet Count, Prothrombin Time) and Chemistry (Glucose (random), Blood Urea Nitrogen, Electrolytes (sodium, potassium, chloride), Creatinine, Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase, Total Bilirubin, Albumin, Total Protein)

Distribution of lymphocyte subsets from peripheral blood was determined by flow cytometry. Flow cytometry is a laser-based technique used to detect and measure physical and chemical characteristics of a population of cells or particles. It allows simultaneous multi-parameter analysis of single cells.

The selected markers of interest, representative of the broader markers were: Total Thymus-cells (T-Cells), Cluster of Differentiation 4 (CD4) T cell subsets, and Cluster of Differentiation 9 (CD8) T cell subset, CD4 T Regulatory (T Reg) cells, Natural Killer Cells, Activated T cells, Myeloid-Derived Suppressor Cells (MSCDs), Monocytes. The Percent Gated and Absolute counts were analysed for each marker. Gating allows the analysis to be restricted to a specific size of cells (e.g. lymphocytes) to allow a more specific analysis. Absolute counting quantifies the total number of cells. It is recommended to look at both values to get the full picture.

Adverse Event of special interest was Skin Photosensitivity. Skin photosensitivity was examined because all subjects who receive Photofrin are photosensitive and must observe precautions to avoid exposure of eyes and skin to direct sunlight or bright indoor lights for 30 days or longer. Changes in skin will be assessed by grade of erythema, edema and blistering and will be tabulated by Common Terminology Criteria for Adverse Events (CTCAE) grade in the dermatology/skin category.