Photodynamic therapy with 3-(1'-hexyloxyethyl) pyropheophorbide-a for early-stage cancer of the larynx: Phase Ib study.

BACKGROUND: The purpose of this study was for us to report results regarding the safety of 3-(1'-hexyloxyethyl) pyropheophorbide-a (HPPH) mediated photodynamic therapy (PDT) in early laryngeal disease, and offer preliminary information on treatment responses. METHODS: A single-institution, phase Ib, open label, noncomparative study of HPPH-PDT in patients with high-risk dysplasia, carcinoma in situ, and T1 squamous cell carcinoma (SCC) of the larynx. The primary outcomes were safety and maximum tolerated dose (MTD), and the secondary outcome was response. RESULTS: Twenty-nine patients and 30 lesions were treated. The most common adverse event (AE) was transient hoarseness of voice. Severe edema, requiring tracheostomy, was the most serious AE, which occurred in 2 patients within several hours of therapy. The MTD was 100 J/cm(2) . Patients with T1 SCC seemed to have good complete response rate (82%) to HPPH-PDT at MTD. CONCLUSION: HPPH-PDT can be safely used to treat early-stage laryngeal cancer, with potential efficacy. © 2015 The Authors Head & Neck Published by Wiley Periodicals, Inc. Head Neck 38: E377-E383, 2016.

Image-guided Interstitial Photodynamic Therapy for Squamous Cell Carcinomas: Preclinical investigation.

OBJECTIVE: Photodynamic therapy (PDT) is a clinically approved minimally invasive treatment for cancer. In this preclinical study, using an imaging-guided approach, we examined the potential utility of PDT in the management of bulky squamous cell carcinomas (SCCs). METHODS: To mimic bulky oropharyngeal cancers seen in the clinical setting, intramuscular SCCs were established in six-to-eight week old female C3H mice. Animals were injected with the photosensitizer, 2-[hexyloxyethyl]-2-devinyl pyropheophorbide-a (HPPH; 0.4 µmol/kg, i.v.) and tumors were illuminated 24 hours post injection with 665 nm light. PDT as a single treatment modality was administered by surface illumination or by interstitial placement of fibers (iPDT). Magnetic resonance imaging was used to guide treatment and assess tumor response to PDT along with correlative histopathologic assessment. RESULTS: Interstitial HPPH-PDT resulted in a marked change on T2 maps 24 hours post treatment compared to untreated controls or transcutaneous illumination. Corresponding apparent diffusion coefficient maps also showed hyperintense areas in tumors following iPDT suggestive of effective photodynamic cell kill. Histologic sections (H&E) confirmed presence of extensive tumor necrosis following iPDT. CONCLUSIONS: These results highlight the potential utility of PDT in the treatment of bulky oropharyngeal cancers. The findings of our study also demonstrate the utility of MRI as a non-invasive tool for mapping of early tissue response to PDT.

Survival differences between organ preservation surgery and definitive radiotherapy in early supraglottic squamous cell carcinoma.

OBJECTIVE: Single-modality treatment, either with organ preservation surgery (OPS) or definitive radiation (RT), is the treatment of choice for patients with early supraglottic squamous cell carcinoma (SGC). However, studies comparing the effectiveness of these 2 techniques are lacking. This study compares the survival outcomes in early SGC patients treated with OPS versus RT. STUDY DESIGN: Secondary data analysis. SETTING: Surveillance, Epidemiology and End Results database. SUBJECTS AND METHODS: This study included adult patients with early-stage (T1N0, T2N0) SGC undergoing single-modality treatment with either OPS (with or without neck dissection [ND]) or RT between 1988 and 2008. Survival analysis was used to compare the overall survival (OS) and disease-specific survival (DSS) between patients treated with OPS+ND, OPS alone, and RT. RESULTS: A total of 2631 T1/T2 N0 SGC patients were identified, of whom 167 (6%) were treated with OPS+ND, 186 (7%) with OPS only, and 2278 patients (87%) with definitive RT only. In stage I (T1N0) SGC patients, a significantly better 5-year DSS was noted for both OPS+ND (81% vs 68%, hazard ratio [HR] = 0.61, P = .03) and OPS only (82% vs 68%, HR = 0.70, P = .05) when compared with definitive RT. For stage II (T2N0) patients, only OPS+ND resulted in a significantly better 5-year DSS (86% vs 60%, HR = 0.31, P < .001) when compared with patients treated with RT. CONCLUSIONS: Patients with early SGC who underwent OPS+ND had better OS and DSS than patients undergoing RT alone. OPS+ND may be considered a viable and preferred treatment option in these patients.

Survival rates and prognostic factors for infiltrating salivary duct carcinoma: Analysis of 228 cases from the Surveillance, Epidemiology, and End Results database.

BACKGROUND: The survival rates and prognostic factors for salivary duct carcinoma (SDC) are not clear. METHODS: Survival estimates and prognostic factors were evaluated for 228 patients with SDC identified from the Surveillance, Epidemiology, and End Results (SEER) database. RESULTS: Median overall survival (OS) duration for patients with SDC was 79 months and 5-year disease-specific survival (DSS) rate was 64%. Among patients with SDC with lymph node involvement, larger primary tumor size (>3 cm) was associated with twice the risk of death (p < .03). Factors predictive of improved DSS were age (p = .01), tumor size (p = .006), tumor grade (p = .02), and lymph node involvement (p < .001). Adjuvant radiotherapy did not improve survival when compared to surgery alone for early-stage (I-II) disease (p = .28). CONCLUSION: Younger patients with SDC (<50 years) showed a better prognosis. Primary tumor size and lymph node involvement were independent and additive risk factors for poor prognosis. The role of adjuvant radiotherapy in the treatment of SDC needs to be explored further.

Pectoralis major myocutaneous flap for reconstruction of circumferential pharyngeal defects.

BACKGROUND: A 270-degree partially tubed pectoralis major myocutaneous flap (PMMF) is an excellent option for total circumferential pharyngoesophageal defects in patients who are not candidates for more complex reconstructions. METHODS: Patients undergoing circumferential pharyngoesophageal reconstruction with partially tubed PMMF were reviewed. End points were stricture, fistula, resumption of oral intake, perioperative death, and recurrence. RESULTS: Eleven patients underwent 270-degree PMMF for reconstruction: 6 (55%) were men and 5 (45%) were women (mean, 62 years; range, 42-78 years). Three patients (27%) developed fistulas and 2 (18%) developed stenosis. Ten patients (91%) were able to resume adequate nutrition via oral intake. There were no perioperative deaths. CONCLUSIONS: Patients with severe comorbidities, metastatic disease, a lack of donor vessels, or a potentially hostile abdomen may not be ideal candidates for free tissue transfer. For these patients, partially tubed PMMF using the prevertebral fascia provides a reliable alternative for reconstruction with excellent functional results.

Vascular priming enhances chemotherapeutic efficacy against head and neck cancer.

PURPOSE: The need to improve chemotherapeutic efficacy against head and neck squamous cell carcinomas (HNSCC) is well recognized. In this study, we investigated the potential of targeting the established tumor vasculature in combination with chemotherapy in head and neck cancer. METHODS: Experimental studies were carried out in multiple human HNSCC xenograft models to examine the activity of the vascular disrupting agent (VDA) 5,6-dimethylxanthenone-4-acetic acid (DMXAA) in combination with chemotherapy. Multimodality imaging (magnetic resonance imaging, bioluminescence) in conjunction with drug delivery assessment (fluorescence microscopy), histopathology and microarray analysis was performed to characterize tumor response to therapy. Long-term treatment outcome was assessed using clinically-relevant end points of efficacy. RESULTS: Pretreatment of tumors with VDA prior to administration of chemotherapy increased intratumoral drug delivery and treatment efficacy. Enhancement of therapeutic efficacy was dependent on the dose and duration of VDA treatment but was independent of the chemotherapeutic agent evaluated. Combination treatment resulted in increased tumor cell kill and improvement in progression-free survival and overall survival in both ectopic and orthotopic HNSCC models. CONCLUSION: Our results show that preconditioning of the tumor microenvironment with an antivascular agent primes the tumor vasculature and results in enhancement of chemotherapeutic delivery and efficacy in vivo. Further investigation into the activity of antivascular agents in combination with chemotherapy against HNSCC is warranted.

Adjuvant intraoperative photodynamic therapy in head and neck cancer.

IMPORTANCE: There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. OBJECTIVES: To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTS: Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. INTERVENTIONS: Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. MAIN OUTCOMES AND MEASURES: Adverse events and highest laser light dose. RESULTS: Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. CONCLUSIONS AND RELEVANCE: The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00470496.

Pretreatment weight status and weight loss among head and neck cancer patients receiving definitive concurrent chemoradiation therapy: implications for nutrition integrated treatment pathways.

PURPOSE: The purpose was to examine the effect of pretreatment weight status on loco-regional progression for patients with squamous cell carcinoma of the head and neck (SCCHN) after receiving definitive concurrent chemoradiation therapy (CCRT). METHODS: In an expanded cohort of 140 patients, we retrospectively reviewed weight status and loco-regional progression of SCCHN patients treated with CCRT between 2004 and 2010. RESULTS: Pretreatment ideal body weight percentage (IBW%) was statistically significantly different for patients with disease progression than for those without progression (p = 0.02) but was not an independent predictor of progression. Median pretreatment IBW% was 118 (72-193) for the progression-free group and was 101.5 (73-163) for the group with progression. Both groups suffered clinically severe weight loss of approximately 9 % from baseline to end treatment. CONCLUSIONS: Pretreatment weight status, a very crude indicator of nutrition status, may have prognostic value in patients with SCCHN undergoing definitive CCRT. Inadequate nutritional status in these patients has been associated with poor clinical outcomes and decreased quality of life. Based on this report and others, the best next steps include routine validated malnutrition screening and the testing of evidence-based nutrition care protocols with the goals of minimizing weight loss and improvement of quality of life.

Cranial base repair with combined vascularized nasal septal flap and autologous tissue graft following expanded endonasal endoscopic neurosurgery.

BACKGROUND: The expanded endonasal endoscopic approach provides excellent visualization and access to midline skull base lesions, albeit with a relatively high risk of postoperative cerebrospinal fluid (CSF) leakage. We present our experience with the expanded endonasal endoscopic approach to the skull base in an institution where, previously, a traditional transsphenoidal approach with a surgical microscope had been used. PATIENTS: We performed a retrospective review to identify patients who underwent expanded endonasal endoscopic surgery and analyzed demographic, pathological, and operative data with particular attention to repair of the skull base defects in 55 procedures performed on 49 patients. We compared the outcomes of 10 primary operations in which we repaired skull base defects using only autologous or allogeneic tissue grafts and 39 primary operations in which we used a vascularized mucoperichondrial nasal septal flap with or without a layered autologous tissue graft. RESULTS: Primary expanded endonasal endoscopic procedures were performed in 49 patients with sellar pathology (33 pituitary adenomas, 4 Rathke's cleft cysts, 1 pituicytoma, 1 pituitary metastasis) and non-sellar pathology (3 meningiomas, 3 clival chordomas, 1 clival mucocele, 1 craniopharyngioma, and 2 esthesioneuroblastomas). Postoperative CSF leakage occurred following 5 of the 49 primary operations (10.2%). This occurred in 2 of 10 primary operations (20.0%) in which the skull base defect was repaired using only autologous and/or allogeneic tissue grafts, necessitating a total of 3 operative CSF leak repairs in those 2 patients. The remaining 3 postoperative CSF leaks occurred in the 39 primary operations (7.7%) in which skull base repair was performed using a mucoperichondrial nasal septal flap, necessitating operative repair in 2 of those patients. CONCLUSION: The repair of skull base defects created during expanded endonasal endoscopic surgery is improved by use of a mucoperichondrial nasal septal flap combined with a layered autologous tissue graft. When CSF leakage occurs despite nasal septal flap closure, the site of the leakage may be easier to localize and repair.

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.

BACKGROUND: 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). METHODS: We conducted a retrospective chart review of patients treated between 2004 and 2010. After a prior analysis, measures were taken to limit therapy beyond 7 weeks. Comparison of outcomes were made between cohorts 1 (2004-2007, n = 78) and 2 (2007-2010, n = 62). RESULTS: Median therapy duration was statistically significantly different between cohorts as follows: 51 days, cohort 1 and 46 days, cohort 2 (p < .01). Locoregional progression in cohorts 1 and 2 was 19% and 5% (p = .01), respectively. On multivariate analysis, patients with prolonged treatment (≥57 days) had an 8-fold increase in risk of locoregional progression compared to patients who completed on time (p < .01). CONCLUSION: Treatment duration was a significant predictor of locoregional progression in patients with SCCHN who received definitive CCRT.

Local inflammation and human papillomavirus status of head and neck cancers.

OBJECTIVE: To determine whether periodontitis is associated with human papillomavirus (HPV) status of head and neck squamous cell carcinoma (HNSCC). DESIGN AND SETTING: Hospital-based case-control study in a comprehensive cancer center. PATIENTS: Evaluation included all patients diagnosed with incident primary squamous cell carcinoma of the oral cavity, oropharynx, and larynx between 1999 and 2007 for whom tissue samples and dental records were available (N = 124). Patients younger than 21 years and those with a history of cancer were excluded. Periodontitis history was assessed by alveolar bone loss in millimeters from panoramic radiographs by one examiner blinded to cancer status. MAIN OUTCOME MEASURE: The presence of HPV-16 DNA in paraffin-embedded tumor samples was identified by polymerase chain reaction. RESULTS: The prevalence of HPV-positive HNSCC was 50 of 124 patients (40.3%). A higher proportion of oropharyngeal cancers were HPV-positive (32 of 49 [65.3%]) compared with oral cavity (9 of 31 [29.0%]) and laryngeal (9 of 44 [20.5%]) cancers. Each millimeter of alveolar bone loss was associated with 2.6 times increased odds (odds ratio [OR], 2.61; 95% CI, 1.58-4.30) of HPV-positive tumor status after adjustment for age at diagnosis, sex, and smoking status. The strength of the association was greater among patients with oropharyngeal SCC (OR, 11.70; 95% CI, 2.09-65.53) compared with those with oral cavity SCC (OR, 2.32; 95% CI, 0.65-8.27) and laryngeal SCC (OR, 3.89; 95% CI, 0.95-15.99). CONCLUSIONS: A history of chronic inflammatory disease in the oral cavity may be associated with tumor HPV status in patients with HNSCC. This association seems to be stronger among patients with oropharyngeal cancer compared with those who have oral cavity or laryngeal SCC.

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

BACKGROUND: 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). METHODS: We performed a retrospective chart review of 78 patients with SCCHN who received definitive CCRT. We compared patient factors, tumor characteristics, and nutritional status indicators between patients with and without locoregional failure. RESULTS: Fifteen of 78 patients (19%) experienced locoregional failure. Median follow-up for live patients was 38 months. On univariate analysis, pretreatment percentage of ideal body weight (%IBW) (p < .01), pretreatment hemoglobin (p = .04), and treatment duration (p < .01) were significant predictors of failure. On multivariate analysis, pretreatment %IBW (p = .04) and treatment time (p < .01) remained statistically significant. CONCLUSIONS: Although treatment time is an accepted risk factor for failure, differences in outcome for patients with head and neck cancer undergoing definitive CCRT based on pretreatment %IBW should be examined further.

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

BACKGROUND: Olfactory Neuroblastoma is a rare malignant tumor of the olfactory tract. Reports in the literature comparing treatment modalities for this tumor are limited. METHODS: The 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. RESULTS: A 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. CONCLUSIONS: Best survival results were obtained for surgery with radiotherapy.

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.

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.

Chronic periodontitis and the incidence of head and neck squamous cell carcinoma.

Substantial evidence supports an association between chronic infections/inflammation, and cancer. The aim of this study was to assess the effect of chronic periodontitis on head and neck squamous cell carcinoma (HNSCC). The study population consisted of new patients at the Department of Dentistry and Maxillofacial Prosthetics, Roswell Park Cancer Institute between 1999 and 2005. Cases were patients diagnosed with primary HNSCC. Controls were all patients seen during the same time period but negative for malignancy. Patients age <21 years, edentulous, immunocompromised, and those with history of cancer were excluded. Periodontitis was measured by alveolar bone loss (ABL) from panoramic radiographs by one examiner blind to cancer status. A total of 473 patients (266 cases and 207 controls) were included in the study. Each millimeter of ABL was associated with >4-fold increased risk of HNSCC (odds ratio, 4.36; 95% confidence interval, 3.16-6.01) after adjustment for age, gender, race/ethnicity, marital status, smoking status, alcohol use, and missing teeth. The strength of the association was greatest in the oral cavity, followed by oropharynx and larynx. The association persisted in subjects who never used tobacco and alcohol. There was a significant interaction between smoking and ABL (P = 0.03). Patients with periodontitis were more likely to have poorly differentiated oral cavity SCC than those without periodontitis (32.8% versus 11.5%; P = 0.038). This study suggests that chronic periodontitis is an independent risk factor for HNSCC and smoking modifies this association. These results have implications for practical and safe strategies for prevention, diagnosis, and treatment of HNSCC.

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.

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 > or = 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.

Chronic periodontitis-human papillomavirus synergy in base of tongue cancers.

OBJECTIVE: To assess whether chronic periodontitis history predicts human papillomavirus (HPV) status in patients with base of tongue cancers. DESIGN: Case-control study using existing patient data. SETTING: Roswell Park Cancer Institute. PATIENTS: Thirty patients newly diagnosed with base of tongue squamous cell carcinoma between 1999 and 2005 for whom both tumor samples and periodontal records were available. Patients younger than 21 years, edentulous, immunocompromised, and those with a history of cancer were excluded. Periodontitis history was assessed on the basis of alveolar bone loss (in millimeters) from panoramic radiographs by one examiner who was blinded to cancer status. MAIN OUTCOME MEASURE: HPV-16 and HPV-18 DNA were identified on paraffin-embedded tumor samples by polymerase chain reaction. Multiple logistic regression was used to estimate odds ratios and 95% confidence intervals. RESULTS: The prevalence of tumors positive for HPV-16 DNA was 21 of 30 (70%). None of the samples were positive for HPV-18 DNA. Compared with participants with HPV-negative tumors, patients with HPV-positive tumors had significantly higher mean alveolar bone loss (3.90 mm vs 2.85 mm, P = .01). After adjustment for age at diagnosis, sex, race/ethnicity, alcohol use, smoking status, and number of missing teeth, every millimeter of alveolar bone loss was associated with an approximately 4-fold (odds ratio, 3.96; 95% confidence interval, 1.18-13.36) increased risk of HPV-positive tumor status. Number of missing teeth was not associated with tumor HPV status (odds ratio, 0.95; 95% confidence interval, 0.74-1.21). CONCLUSIONS: Chronic periodontitis may be a significant factor in the natural history of HPV infection in patients with base of tongue cancers. Additional confirmation in larger studies is required.