Saurin R. Popat

Photodynamic Therapy for Head and Neck Dysplasia and Cancer

OBJECTIVE To determine the response of dysplasia, carcinoma in situ (CIS), and T1 carcinoma of the oral cavity and larynx to photodynamic therapy with porfimer sodium. DESIGN Prospective trial. SETTING A National Cancer Institute-designated cancer institute. PATIENTS Patients with primary or recurrent moderate to severe oral or laryngeal dysplasia, CIS, or T1N0 carcinoma. INTERVENTION Porfimer sodium, 2 mg/kg of body weight, was injected intravenously 48 hours before treatment. Light at 630 nm for photosensitizer activation was delivered from an argon laser or diode laser using lens or cylindrical diffuser fibers. The light dose was 50 J/cm(2) for dysplasia and CIS and 75 J/cm(2) for carcinoma. MAIN OUTCOME MEASURES Response was evaluated at 1 week and at 1 month and then at 3-month intervals thereafter. Response options were complete (CR), partial (PR), and no (NR) response. Posttreatment biopsies were performed in all patients with persistent and recurrent visible lesions. RESULTS Thirty patients were enrolled, and 26 were evaluable. Mean follow-up was 15 months (range, 7-52 months). Twenty-four patients had a CR, 1 had a PR, and 1 had NR. Three patients with oral dysplasia with an initial CR experienced recurrence in the treatment field. All the patients with NR, a PR, or recurrence after an initial CR underwent salvage treatment. Temporary morbidities included edema, pain, hoarseness, and skin phototoxicity. CONCLUSION Photodynamic therapy with porfimer sodium is an effective treatment alternative, with no permanent sequelae, for oral and laryngeal dysplasia and early carcinoma. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00530088.

Human papillomavirus types 16 and 18 in epithelial dysplasia of oral cavity and oropharynx: A meta-analysis, 1985–2010

Human papillomavirus (HPV) types 16 and 18 are causally related to a sub-set of oral cavity and oropharyngeal squamous cell cancers. However, a clear estimate of the prevalence of HPV-16/18 in oral cavity and oropharyngeal dysplasia (OOPD) is not available. This literature review and meta-analysis was conducted to provide a prevalence estimate for HPV-16/18 in OOPD. Twenty-two studies that reported prevalence of HPV-16 and/or 18 in 458 OOPD lesions were analyzed. Meta-analysis was used to evaluate the prevalence of HPV-16/18 and logistic regression was used for stratified analysis by age, gender, and histological grade. The overall prevalence of HPV-16/18 in OOPD lesions was 24.5% [95% confidence interval (CI), 16.4-36.7%)]. The individual prevalence for HPV-16 alone was 24.4%. The prevalence of HPV-16/18 in oral cavity lesions alone was 25.3% (95% CI, 14.2-45.2%). The odds of detection of HPV-16/18 in dysplastic lesions in males were twice that of females [odds ratio (OR), 2.44]. HPV-16/18 were 3 times more common in dysplastic lesions (OR, 3.29; 95% CI, 1.95-5.53%) and invasive cancers (OR, 3.43; 95% CI, 2.07-5.69%), when compared to normal biopsies. There was no significant difference in HPV-16/18 rates between dysplastic lesions and cancers or between mild, moderate or severe dysplastic lesions. This meta-analysis provides a quantification of the prevalence of HPV types 16/18 in OOPD lesions. These results also support the assumption that HPV-16/18 infection occurs during the early phase of the oral cavity and oropharyngeal carcinogenesis.

Improved survival following surgery and radiation therapy for olfactory neuroblastoma: analysis of the SEER database.

BackgroundOlfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited.MethodsThe SEER database (1973-2006) was queried by diagnosis code to identify patients with Olfactory Neuroblastoma. Kaplan-Meier was used to estimate survival distributions based on treatment modality. Differences in survival distributions were determined by the log-rank test. A Cox multiple regression analysis was then performed using treatment, race, SEER historic stage, sex, age at diagnosis, year at diagnosis and SEER geographic registry.ResultsA total of 511 Olfactory Neuroblastoma cases were reported. Five year overall survival, stratified by treatment modality was: 73% for surgery with radiotherapy, 68% for surgery only, 35% for radiotherapy only, and 26% for neither surgery nor radiotherapy. There was a significant difference in overall survival between the four treatment groups (p < 0.01). At ten years, overall survival stratified by treatment modality and stage, there was no significant improvement in survival with the addition of radiation to surgery.ConclusionsBest survival results were obtained for surgery with radiotherapy.

Radiation Treatment Interruptions Greater Than One Week and Low Hemoglobin Levels (12 g/dL) are Predictors of Local Regional Failure After Definitive Concurrent Chemotherapy and Intensity- Modulated Radiation Therapy for Squamous Cell Carcinoma of the Head and Neck

Purpose:To determine whether baseline hemoglobin level and radiation treatment interruptions predict for loco-regional failure after intensity-modulated radiation therapy (IMRT) with concurrent chemotherapy for definitive treatment of squamous cell carcinoma of the head and neck (SCCHN). Methods:This retrospective review identified 78 consecutive patients treated with definitive concurrent chemoradiation for SCCHN. Patients were treated with IMRT to 70 Gy in 35 daily fractions to the high-dose target volume and 56 Gy to the elective target volume. Results:Median age of the cohort was 62 (37–81). Median follow-up was 12 months. Tumor sites included: oropharynx (54%), larynx (36%), oral cavity (5%), and hypopharynx (5%). Fifteen of 78 patients (19%) experienced loco-regional failure. These included: 6 primary site failures, 5 regional failures, and 4 failures in both the primary site and regional lymph nodes. All but one failure occurred in the high-dose target volume. Only duration of radiation treatment and baseline hemoglobin levels were significant predictors of local control. Loco-regional failure occurred in 6 of 13 patients (46%) with radiation treatment interruptions (>1 week) versus 9 of 65 patients (14%) completing radiation therapy without interruption (P = 0.0148). Loco-regional failure occurred in 7 of 19 patients (37%) whose pretreatment hemoglobin level was <12 g/dL compared with 8 of 59 patients (14%) with hemoglobin levels ≥12 (P = 0.042). Conclusion:Overall radiation treatment time and pretreatment hemoglobin level were significant predictors for loco-regional failure after definitive concurrent chemotherapy and IMRT for SCCHN.

Autofluorescence-guided surveillance for oral cancer.

Early detection of oral premalignant lesions (OPL) and oral cancers (OC) is critical for improved survival. We evaluated if the addition of autofluorescence visualization (AFV) to conventional white-light examination (WLE) improved the ability to detect OPLs/OCs. Sixty high-risk patients, with suspicious oral lesions or recently diagnosed untreated OPLs/OCs, underwent sequential surveillance with WLE and AFV. Biopsies were obtained from all suspicious areas identified on both examinations (n = 189) and one normal-looking control area per person (n = 60). Sensitivity, specificity, and predictive values were calculated for WLE, AFV, and WLE + AFV. Estimates were calculated separately for lesions classified by histopathologic grades as low-grade lesions, high-grade lesions (HGL), and OCs. Sequential surveillance with WLE + AFV provided a greater sensitivity than WLE in detecting low-grade lesions (75% versus 44%), HGLs (100% versus 71%), and OCs (100% versus 80%). The specificity in detecting OPLs/OCs decreased from 70% with WLE to 38% with WLE + AFV. Thirteen of the 76 additional biopsies (17%) obtained based on AFV findings were HGLs/OCs. Five patients (8%) were diagnosed with a HGL/OC only because of the addition of AFV to WLE. In seven patients, additional HGL/OC foci or wider OC margins were detected on AFV. Additionally, AFV aided in the detection of metachronous HGL/OC in 6 of 26 patients (23%) with a history of previously treated head and neck cancer. Overall, the addition of AFV to WLE improved the ability to detect HGLs/OCs. In spite of the lower specificity, AFV + WLE can be a highly sensitive first-line surveillance tool for detecting OPLs/OCs in high-risk patients.

Pretreatment nutritional status and locoregional failure of patients with head and neck cancer undergoing definitive concurrent chemoradiation therapy.

This study was carried out to determine if markers of nutritional status predict for locoregional failure following intensity‐modulated radiation therapy (IMRT) with concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN).

Quantification of the effect of treatment duration on local-regional failure after definitive concurrent chemotherapy and intensity-modulated radiation therapy for squamous cell carcinoma of the head and neck

The purpose of this study was to quantify the effect of treatment duration on locoregional progression after definitive concurrent chemoradiation (CCRT) for squamous cell carcinoma of the head and neck (SCCHN).

Establishment and Characterization of Patient Tumor-Derived Head and Neck Squamous Cell Carcinoma Xenografts

The overall purpose of this study was to establish human head and neck squamous cell carcinoma (HNSCC) xenografts in mice by transplantation of surgical tumor tissue and to characterize the growth, histologic and vascular properties of these xenografts. Primary surgical specimens of HNSCC were xenografted into eight-to-twelve week old severe combined immunodeficiency (SCID) mice. Histologic features of primary HNSCC specimens, initial and established xenografts were compared for tumors established from three different head and neck subsites, namely, oral cavity, larynx and base of tongue(one tumor per site). Growth rates of xenografts were compared along with magnetic resonance imaging (MRI) measures of tumor vascularity and correlative CD31 immunostaining. Initial and established xenografts from all three sites demonstrated a squamous phenotype similar to the original patient tumor histology. Established xenografts of oral cavity and larynx exhibited increased keratinization (H&E) compared to initial xenografts and the primary tumor. No differences in tumor growth rates were observed between established xenografts from the different subsites. Xenografts established from SCC of the larynx exhibited increased microvessel density and lumen area (CD31 staining) along with enhanced permeability to the MR contrast agent compared to oral cavity and base of tongue tumors. Our results show that the combination of non-invasive imaging along with histologic evaluation of patient tumor xenografts offers a valuable platform for preclinical investigations in head and neck cancer. However, it is important to recognize the influence of tumor-host interactions on the histologic phenotype of transplanted tumors.

Management of an acquired tracheoesophageal fistula with a fascial free flap.

Failure in the primary repair of a benign acquired tracheoesophageal fistula limits the operative options available at revision. Use of a fascial free flap to treat this condition has not been previously reported.

Combined use of covered stent and flow diversion to seal iatrogenic carotid injury with vessel preservation during transsphenoidal endoscopic resection of clival tumor.

Background: Transsphenoidal tumor resection can lead to internal carotid artery (ICA) injury. Vascular disruption is often treated with emergent vessel deconstruction, incurring complications in a subset of patients with poor collateral circulation and resulting in minor and major ischemic strokes. Methods: We attempted a novel approach combining a covered stent graft (Jostent) and two flow diverter stents [Pipeline embolization devices (PEDs)] to treat active extravasation from a disrupted right ICA that was the result of a transsphenoidal surgery complication. This disruption occurred during clival tumor surgery and required immediate sphenoidal sinus packing. Emergent angiography revealed continued petrous carotid artery extravasation, warranting emergent vessel repair or deconstruction for treatment. To preserve the vessel, we utilized a covered Jostent. Due to tortuosity and lack of optimal wall apposition, there was reduced, yet persistent extravasation from an endoleak after Jostent deployment that failed to resolve despite multiple angioplasties. Therefore, we used PEDs to divert the flow. Results: Flow diversion relieved the extravasation. The patient remained neurologically intact post-procedure. Conclusions: This case demonstrates successful combined use of a covered stent and flow diverters to treat acute vascular injury resulting from transsphenoidal surgery. However, concerns remain, including the requirement of dual antiplatelet agents increasing postoperative bleeding risks, stent-related thromboembolic events, and delayed in-stent restenosis rates.