Clinical evaluation of a mobile, low-cost system for fluorescence guided photodynamic therapy of early oral cancer in India.

BACKGROUND: Morbidity and mortality due to oral cancer in India are exacerbated by a lack of access to effective treatments amongst medically underserved populations. We developed a user-friendly low-cost, portable fibre-coupled LED system for photodynamic therapy (PDT) of early oral lesions, using a smartphone fluorescence imaging device for treatment guidance, and 3D printed fibreoptic attachments for ergonomic intraoral light delivery. METHODS: 30 patients with T1N0M0 buccal mucosal cancer were recruited from the JN Medical College clinics, Aligarh, and rural screening camps. Tumour limits were defined by external ultrasound (US), white light photos and increased tumour fluorescence after oral administration of the photosensitising agent ALA (60 mg/kg, divided doses), monitored by a smartphone fluorescence imaging device. 100 J/cm2 LED light (635 nm peak) was delivered followed by repeat fluorescence to assess photobleaching. US and biopsy were repeated after 7-17 days. This trial is registered with ClinicalTrials.gov, NCT03638622, and the study has been completed. FINDINGS: There were no significant complications or discomfort. No sedation was required. No residual disease was detected in 22 out of 30 patients who completed the study (26 of 34 lesions, 76% complete tumour response, 50 weeks median follow-up) with up to 7.2 mm depth of necrosis. Treatment failures were attributed to large tumour size and/or inadequate light delivery (documented by limited photobleaching). Moderately differentiated lesions were more responsive than well-differentiated cancers. INTERPRETATION: This simple and low-cost adaptation of fluorescenceguided PDT is effective for treatment of early-stage malignant oral lesions and may have implications in global health.

Clinical evaluation of smartphone-based fluorescence imaging for guidance and monitoring of ALA-PDT treatment of early oral cancer.

SIGNIFICANCE: India has one of the highest rates of oral cancer incidence in the world, accounting for 30% of reported cancers. In rural areas, a lack of adequate medical infrastructure contributes to unchecked disease progression and dismal mortality rates. Photodynamic therapy (PDT) has emerged as an effective modality with potential for treating early stage disease in resource-limited settings, while photosensitizer fluorescence can be leveraged for treatment guidance. AIM: Our aim was to assess the capability of a simple smartphone-based device for imaging 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) fluorescence for treatment guidance and monitoring as part of an ongoing clinical study evaluating low-cost technology for ALA-based PDT treatment of early oral cancer. APPROACH: A total of 29 subjects with <2 cm diameter moderately/well-differentiated microinvasive ( < 5 mm depth) oral squamous cell carcinoma lesions (33 lesions total, mean area ∼1.23 cm2) were administered 60 mg / kg ALA in oral solution and imaged before and after delivery of 100 J / cm2 total light dose to the lesion surface. Smartphone-based fluorescence and white light (WL) images were analyzed and compared with ultrasound (US) imaging of the same lesions. RESULTS: We present a comparative analysis of pre- and post-treatment fluorescence, WL, and US images of oral lesions. There was no significant difference in the distribution of lesion widths measured by fluorescence and US (mean widths of 14.5 and 15.3 mm, respectively) and linear regression shows good agreement (R2 = 0.91). In general, PpIX fluorescence images obtained prior to therapeutic light delivery are able to resolve lesion margins while dramatic photobleaching (∼42 % ) is visible post-treatment. Segmentation of the photobleached area confirms the boundaries of the irradiated zone. CONCLUSIONS: A simple smartphone-based approach for imaging oral lesions is shown to agree in most cases with US, suggesting that this approach may be a useful tool to aid in PDT treatment guidance and monitoring photobleaching as part of a low-cost platform for intraoral PDT.

Interdigitated versus sequential high-dose-rate intracavitary brachytherapy with external beam radiotherapy in locally advanced carcinoma cervix.

AIMS: To decrease overall treatment time (OTT) and to compare the clinical outcome of interdigitated high-dose-rate intracavitary brachytherapy (HDRICBT) versus sequential HDRICBT with external beam radiotherapy (EBRT) in the treatment of locally advanced carcinoma cervix. METHODS: Eighty-two patients with histologically confirmed carcinoma of the cervix, untreated International Federation of Gynecology and Obstetrics Stage IIB-IIIB, were included and randomized into two groups. The study group received EBRT 50 Gy/25 fractions with interdigitated HDRICBT 8 Gy/fraction weekly a total of three fractions. Patients in the control group received EBRT 50 Gy/25 fractions with sequential HDRICBT 8 Gy/fraction weekly a total of three fractions. At the end of the study, results of both groups compared in terms of OTT, acute and late toxicities, and response to therapy clinically. RESULTS: A total of 82 patients were enrolled 41 in each arm. Seventy-two patients completed treatment and were analyzed. Mean OTT in study group and control group was 40 and 60 days, respectively. The median follow-up duration was 10 months (3-18). Most of the acute and late toxicities were of Grade 1 and 2 type and comparable in both study and control groups. Treatment interruption due to treatment-related toxicity was slightly higher in the study group than the control group, but it was statistically insignificant. Os negotiability was not found to be a limiting factor for interdigitated HDRICBT. CONCLUSION: Interdigitated HDRICBT has equivalent response and toxicities as sequential HDRICBT with the advantage of significant reduction in OTT.