Long-term Outcomes with Nivolumab as First-line Treatment in Recurrent or Metastatic Head and Neck Cancer: Subgroup Analysis of CheckMate 141.

In the randomized, phase 3 CheckMate 141 trial, nivolumab significantly improved overall survival (OS) versus investigator's choice (IC) of chemotherapy at primary analysis among 361 patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) post-platinum therapy. Nivolumab versus IC as first-line treatment also improved OS among patients with R/M SCCHN who progressed on platinum therapy for locally advanced disease in the adjuvant or primary setting at 1-year follow-up. In the present long-term follow-up analysis of patients receiving first-line treatment, OS benefit with nivolumab (n = 50) versus IC (n = 26) was maintained (median: 7.7 months versus 3.3 months; hazard ratio: 0.56; 95% confidence interval, 0.34-0.94) at 2 years. No new safety signals were identified. In summary, this long-term 2-year analysis of CheckMate 141 supports the use of nivolumab as a first-line treatment for patients with platinum-refractory R/M SCCHN.

Two-year follow-up of a randomized phase III clinical trial of nivolumab vs. the investigator's choice of therapy in the Asian population for recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141).

BACKGROUND: The present study evaluated the 2-year survival of the Asian population in the CheckMate 141 trial. METHODS: The CheckMate 141 trial included patients with recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN). In the present study, 34 Asian patients (nivolumab group: 23 patients; investigator's choice of therapy [IC] group: 11 patients) were analyzed. RESULTS: The median overall survival (OS) was 12.1 and 6.2 months for the nivolumab and IC groups, respectively. The estimated 2-year OS rates were 22.7% and 0% for the nivolumab and IC groups, respectively. In the nivolumab group, the patients with any treatment-related adverse events (TRAEs), including skin-related disorders, showed better OS than the patients without any TRAEs. CONCLUSIONS: Nivolumab demonstrated prolonged OS benefits in the Asian population with platinum-refractory R/M SCCHN and a favorable safety profile. TRAEs, including skin-related disorders, may be favorable prognostic factors for nivolumab efficacy. CLINICAL TRIAL REGISTRATION: NCT02105636.

Nivolumab versus investigator's choice in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: Efficacy and safety in CheckMate 141 by age.

OBJECTIVES: Many patients with squamous cell carcinoma of the head and neck (SCCHN) are ≥65 years old; comorbidities and other age-related factors may affect their ability to tolerate traditional chemotherapy. Nivolumab is the only immunotherapy to significantly improve overall survival (OS) versus investigator's choice (IC) of single-agent chemotherapy at primary analysis in a phase 3 trial (CheckMate 141) in patients with recurrent/metastatic SCCHN post-platinum therapy. In this post hoc analysis, we report efficacy and safety by age. PATIENTS AND METHODS: Eligible patients were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks (n = 240) or IC (methotrexate, docetaxel, or cetuximab n = 121). The primary endpoint of the trial was OS. For this analysis, outcomes were analyzed by age < 65 and ≥65 years. The data cut-off date was September 2017 (minimum follow-up 24.2 months). RESULTS: At baseline, 68 patients (28.3%) receiving nivolumab and 45 patients (37.2%) receiving IC were ≥65 years. Baseline characteristics were generally similar across age groups. OS and tumor response benefits with nivolumab versus IC were maintained regardless of age. The 30-month OS rates of 11.2% (<65 years) and 13.0% (≥65 years) with nivolumab were more than tripled versus corresponding IC rates of 1.4% and 3.3%, respectively. The nivolumab arm had a lower rate of treatment-related adverse events versus IC regardless of age, consistent with the overall patient population. CONCLUSION: In CheckMate 141, nivolumab resulted in a higher survival versus IC in patients <65 and ≥65 years, with a manageable safety profile in both age groups. ClinicalTrials.gov: NCT02105636.

Nivolumab treatment beyond RECIST-defined progression in recurrent or metastatic squamous cell carcinoma of the head and neck in CheckMate 141: A subgroup analysis of a randomized phase 3 clinical trial.

BACKGROUND: Response patterns with immune checkpoint inhibitors may be different from those with chemotherapy. Therefore, assessment of response to immunotherapy with the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, could result in premature treatment termination. The randomized, open-label, phase 3 CheckMate 141 trial (NCT02105636), which evaluated nivolumab in recurrent/metastatic squamous cell carcinoma of the head and neck after platinum therapy, allowed treatment beyond first RECIST-defined progression (TBP) according to protocol-specified criteria. METHODS: In CheckMate 141, patients with RECIST-defined progression who had a stable performance status and demonstrated clinical benefit without rapid disease progression were permitted to receive TBP with nivolumab at 3 mg/kg every 2 weeks until further progression, which was defined as an additional ≥10% increase in tumor volume. This post hoc analysis evaluated outcomes for patients who received TBP with nivolumab. RESULTS: Of 240 patients randomized to nivolumab, 146 experienced RECIST-defined progression. Sixty-two of these patients received TBP, and 84 discontinued treatment (no TBP). Among the 60 TBP patients evaluable for response, 15 (25%) had no change in their tumor burden, and 15 (25%) had reductions in target lesion size; 3 patients (5%) had reductions >30%. The median overall survival among TBP patients was 12.7 months (95% confidence interval, 9.7-14.6 months). No new safety signals were observed with TBP. Exploratory analyses of immune cell biomarkers suggested a potential relationship with initial and TBP responses. CONCLUSIONS: Tumor burden reduction was noted in a proportion of patients who received TBP with nivolumab in CheckMate 141. Additional research is warranted to identify factors predictive of a TBP benefit in this population.

Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression.

OBJECTIVES: We report 2-year results from CheckMate 141 to establish the long-term efficacy and safety profile of nivolumab and outcomes by tumor PD-L1 expression in patients with recurrent or metastatic (R/M),platinum-refractory squamous cell carcinoma of the head and neck (SCCHN). METHODS: Patients with R/M SCCHN with tumor progression/recurrence within 6 months of platinum therapy were randomized 2:1 to nivolumab 3 mg/kg every 2 weeks or investigator's choice (IC). Primary endpoint: overall survival (OS). Data cutoff: September 2017. RESULTS: With 24.2 months' minimum follow-up, nivolumab (n = 240) continued to improve OS vs IC (n = 121), hazard ratio (HR) = 0.68 (95% CI 0.54-0.86). Nivolumab nearly tripled the estimated 24-month OS rate (16.9%) vs IC (6.0%), and demonstrated OS benefit across patients with tumor PD-L1 expression ≥1% (HR [95% CI] = 0.55 [0.39-0.78]) and  < 1% (HR [95% CI] = 0.73 [0.49-1.09]), and regardless of tumor HPV status. Estimated OS rates at 18, 24, and 30 months with nivolumab were consistent irrespective of PD-L1 expression (<1%/≥1%). In the nivolumab arm, there were no observed differences in baseline characteristics or safety profile between long-term survivors and the overall population. Grade 3-4 treatment-related adverse event rates were 15.3% and 36.9% for nivolumab and IC, respectively. CONCLUSION: Nivolumab significantly improved OS at the primary analysis and demonstrated prolonged OS benefit vs IC and maintenance of a manageable and consistent safety profile with 2-year follow-up. OS benefit was observed with nivolumab irrespective of PD-L1 expression and HPV status. (Clinicaltrials.gov: NCT02105636).

Cancer stem cell and its niche in malignant progression of oral potentially malignant disorders.

OBJECTIVE: The purpose of this study was to determine association between cancer stem cells (CSCs) and their niche with progression of oral potentially malignant disorders. MATERIALS AND METHODS: Patients with histologically confirmed oral potentially malignant disorders, stratified into high/low risk lesions based on the degree of dysplasia and oral cancer were included in this study. Immunohistochemical profiling of markers of CSCs (CD44), endothelial cells (CD31) and CSC-vascular niche cross-talk (CXCR4 and SDF1) were carried out. Statistical analysis was performed to correlate the relationship of markers with histopathology grade (ANOVA, and χ2 test, unpaired t test) using GraphPad InStat v3.06. RESULTS: The study included 550 samples (349 patients) and analysis showed progressive increase in expression levels of CSC and its niche markers with increase in grade of dysplasia as compared to the normal cohort (p < 0.05). Co-expression analysis revealed that, in comparison to the normal cohort, a larger percentage of patients showed increased expression of CD31 and CD44 (CD31high/CD44high; p < 0.05) and of CXCR4 and SDF1 (CXCR4high/SDF1high; p = 0.04), suggesting an association of the CSCs and the vascular niche. Further, distribution of patients with CD44high/CXCR4high (p < 0.05) and CD31high/SDF1high (p = 0.01) was significantly increased in the high-risk group (18%), suggesting a correlation between CD44+/CXCR4+ cells, the vascular niche and progression of oral dysplastic lesions. CONCLUSION: The increased expression of CSCs, the vascular niche and their cross talk markers are associated with increase in severity of dysplasia suggesting their role in the progression of oral potentially malignant disorders and may hence be used in identifying high-risk OPMD.

Correlation of Symptoms, Clinical Signs, and Biomarkers of Inflammation in Postsurgical Chronic Rhinosinusitis.

OBJECTIVE: The study aimed to evaluate symptoms described by patients with chronic rhinosinusitis with polypoid changes/nasal polyps and their correlation with computed tomography (CT), nasal endoscopy, and intranasal biomarkers. STUDY DESIGN: Prospective multicenter study symptom data from postsurgical adult chronic rhinosinusitis study participants with recurrent disease refractory to medical therapy were analyzed in comparison with objective data. METHODS: Using logistic regression analysis, participant-rated 16-question surveys from 258 participants were assessed for correlation with nasal endoscopy scores, CT percentage of sinus occlusion, and intranasal biomarkers of fungal antigens (Alternaria and Aspergillus), eosinophilic inflammation (eosinophil-derived neurotoxin [EDN] and major basic protein [MBP]), and inflammatory cytokines (interleukins 5 and 13). RESULTS: Study participant assessments revealed increased CT occlusion in participants presenting with greater inability to smell ( P < .019). Mucosal inflammation identified on nasal endoscopy was positively correlated with congestion ( P < .028), runny nose ( P < .002), and ear pain ( P < .007). Elevated EDN was positively correlated in patients with bothersome congestion ( P < .031) and runny nose ( P < .011). Sneezing was positively correlated with multiple markers: Alternaria ( P < .024), interleukin-13 ( P < .027), MBP ( P < .034), and interleukin-5 ( P < .019). CONCLUSION: Nasal endoscopy, not CT imaging, has the strongest correlation with the 2 cardinal symptoms of congestion and runny nose in CRS patients; these correlate with biomarkers of eosinophilic inflammation.

Subsite variation in survival of oropharyngeal squamous cell carcinomas 2004 to 2011.

OBJECTIVES/HYPOTHESIS: To evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors. STUDY DESIGN: Retrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011. METHODS: The cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival. RESULTS: The cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa. CONCLUSIONS: In this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:1087-1092, 2017.

A Randomized Double-Blind Placebo-Controlled Phase IIB Trial of Curcumin in Oral Leukoplakia.

Oral leukoplakia is a potentially malignant lesion of the oral cavity, for which no effective treatment is available. We investigated the effectiveness of curcumin, a potent inhibitor of NF-κB/COX-2, molecules perturbed in oral carcinogenesis, to treat leukoplakia. Subjects with oral leukoplakia (n = 223) were randomized (1:1 ratio) to receive orally, either 3.6 g/day of curcumin (n = 111) or placebo (n = 112), for 6 months. The primary endpoint was clinical response obtained by bi-dimensional measurement of leukoplakia size at recruitment and 6 months. Histologic response, combined clinical and histologic response, durability and effect of long-term therapy for an additional six months in partial responders, safety and compliance were the secondary endpoints. Clinical response was observed in 75 (67.5%) subjects [95% confidence interval (CI), 58.4-75.6] in the curcumin and 62 (55.3%; 95% CI, 46.1-64.2) in placebo arm (P = 0.03). This response was durable, with 16 of the 18 (88.9%; 95% CI, 67.2-96.9) subjects with complete response in curcumin and 7 of 8 subjects (87.5%) in placebo arm, demonstrating no relapse after 6 months follow-up. Difference in histologic response between curcumin and placebo was not significant (HR, 0.88, 95% CI, 0.45-1.71; P = 0.71). Combined clinical and histologic response assessment indicated a significantly better response with curcumin (HR, 0.50; 95% CI, 0.27-0.92; P = 0.02). Continued therapy, in subjects with partial response at 6 months, did not yield additional benefit. The treatment did not raise any safety concerns. Treatment of oral leukoplakia with curcumin (3.6 g for six months), thus was well tolerated and demonstrated significant and durable clinical response for 6 months. Cancer Prev Res; 9(8); 683-91. ©2016 AACR.

Smoking cessation is associated with improved survival in oropharynx cancer treated by chemoradiation.

OBJECTIVES/HYPOTHESIS: The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN: Retrospective review. METHODS: Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS: Of 120 evaluable patients, 71% had HPV+ tumors. Median follow-up duration for the entire cohort was 41.5 months (range = 6-88 months). HPV+ current smokers experienced significantly worse 5-year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV- current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35-10.0). Similarly, current smokers with HPV- tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS: Current smoking is associated with poor prognosis, independent of HPV status, in CCRT-treated OPSCC patients. Current smoking produced an approximately four- to sevenfold increase in risk of mortality for HPV+ and HPV- patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:2733-2738, 2016.

Progression of gingival squamous cell carcinoma from early to late stage after invasive dental procedure.

Early presentation of gingival squamous cell carcinoma (GSCC) is at times misdiagnosed as a benign inflammatory or reactive oral condition. Some misdiagnosed patients undergo unnecessary, invasive dental procedures, resulting in delayed cancer diagnosis and an increased risk of accelerated disease progression due to disruption of the periosteum and cortical bone. The records of 58 patients with biopsy-proven GSCC were retrospectively reviewed. The sample included 32 patients who underwent an invasive dental procedure (IDP) prior to cancer diagnosis and 26 patients who did not undergo an IDP (non-case group). Patients from both groups initially presented with similar symptoms. The median duration of symptoms at initial clinical presentation was 6 months for the IDP group and 2 months for the non-case group. In IDP patients, symptoms worsened after the IDP was rendered, with 37.5% presenting with a severe-grade symptom. In both groups, the majority of lesions were found on the posterior mandible and had a histologic grading of moderately differentiated GSCC. The odds of the IDP group having late-stage disease were 2.94 times greater than the odds for the control group. Stage T3/T4 malignancy was diagnosed in 77.4% of the IDP patients versus 53.8% of non-case patients. Disease-specific mortality was comparable; however, surgical treatment was significantly more extensive in the IDP group than in the non-case group. The disruption of alveolar periosteum in undiagnosed oral cancer patients results in significant delay in diagnosis, necessitating more complicated treatment regimens because of local tumor progression.

An Analysis of Current Techniques Used for Intraoperative Flap Evaluation.

BACKGROUND: Over the last decade, microsurgeons have used a greater variety of more complex flaps. At the same time, microsurgeons have also become more interested in technology, such as indocyanine green (ICG) angiography, dynamic infrared thermography (DIRT), and photospectrometry, for preoperative planning and postoperative monitoring. These technologies are now migrating into the operating room, and are used to optimize flap design and to identify areas of hypoperfusion or problems with the anastomoses. Although relatively more has been published about ICG angiography, information is generally lacking about the intraoperative role of these techniques. METHODS: A systematic analysis of articles discussing intraoperative ICG angiography, DIRT, and photospectrometry was performed to better define the sensitivity, specificity, expected outcomes, and potential complications associated with these techniques. RESULTS: For intraoperative ICG angiography, the sensitivity was 90.9% (95% CI: 77.5-100) and the accuracy was 98.6% (95% CI: 97.6-99.7). The sensitivity of DIRT was 33% (95% CI: 11.3-64.6), the specificity was 100% (95% CI: 84.9-100), and the accuracy was 80% (95% CI: 71.2-89.7). The sensitivity of intraoperative photospectrometry was 92% (95% CI: 72.4-98.6), the specificity was 100% (95% CI: 98.8-100), and the accuracy was also 100% (95% CI: 98.7-100). CONCLUSION: These technologies for intraoperative perfusion assessment have the potential to provide objective data that may improve decisions about flap design and the quality of microvascular anastomoses. However, more work is needed to clearly document their value.

Folate intake and the risk of oral cavity and pharyngeal cancer: a pooled analysis within the International Head and Neck Cancer Epidemiology Consortium.

There are suggestions of an inverse association between folate intake and serum folate levels and the risk of oral cavity and pharyngeal cancers (OPCs), but most studies are limited in sample size, with only few reporting information on the source of dietary folate. Our study aims to investigate the association between folate intake and the risk of OPC within the International Head and Neck Cancer Epidemiology (INHANCE) Consortium. We analyzed pooled individual-level data from ten case-control studies participating in the INHANCE consortium, including 5,127 cases and 13,249 controls. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were estimated for the associations between total folate intake (natural, fortification and supplementation) and natural folate only, and OPC risk. We found an inverse association between total folate intake and overall OPC risk (the adjusted OR for the highest vs. the lowest quintile was 0.65, 95% CI: 0.43-0.99), with a stronger association for oral cavity (OR = 0.57, 95% CI: 0.43-0.75). A similar inverse association, though somewhat weaker, was observed for folate intake from natural sources only in oral cavity cancer (OR = 0.64, 95% CI: 0.45-0.91). The highest OPC risk was observed in heavy alcohol drinkers with low folate intake as compared to never/light drinkers with high folate (OR = 4.05, 95% CI: 3.43-4.79); the attributable proportion (AP) owing to interaction was 11.1% (95% CI: 1.4-20.8%). Lastly, we reported an OR of 2.73 (95% CI:2.34-3.19) for those ever tobacco users with low folate intake, compared with nevere tobacco users and high folate intake (AP of interaction =10.6%, 95% CI: 0.41-20.8%). Our project of a large pool of case-control studies supports a protective effect of total folate intake on OPC risk.

Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

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.

Socioeconomic factors and the risk for sarcoma.

Sarcomas are a heterogeneous group of rare malignancies arising from mesenchymal tissue. Although several occupational exposures have been evaluated in association with sarcoma, little is known about the role of socioeconomic indicators such as education. Socioeconomic status has been found to be associated with risk of development of several types of cancers, primarily lung, gastric, and cervical cancers. We conducted a hospital-based case-control study to evaluate the association of socioeconomic level with the risk for sarcoma. A total of 371 incident cases of sarcoma were matched in terms of age, sex, and year of enrollment in the study with 742 cancer-free controls. Education and income levels were evaluated as the indicators of socioeconomic status. Higher education (college level) was associated with a significantly lower risk for sarcoma [odds ratio (OR)=0.48, 95% confidence interval (CI)=0.29-0.80], even after adjusting for important confounders. After stratifying by sex, significantly lower risk for sarcoma was observed among men who had college level education compared with men with a level of education of eighth grade or lower (OR=0.38, 95% CI=0.19-0.74). A significant association between education and the risk for sarcoma remained after stratifying by income (OR=0.49, 95% CI=0.28-0.86, among the low income group). When analyzed as a composite exposure, individuals with high education and high income status had significantly lower risk for sarcoma compared with those with low income and low education status (OR=0.41, 95% CI=0.23-0.71). Thus, socioeconomic factors may play a significant role in determining the risk for sarcoma and should be explored further to elucidate the underlying factors that may explain these sociodemographic inequalities related to sarcoma.

Osteonecrosis of the jaw - prevention and treatment strategies for oral health professionals.

Patients diagnosed with multiple myeloma and metastatic breast, prostate and renal cancers have a better opportunity for longer survival due to a myriad of chemotherapies regimens that attempt to manage disease progression while decreasing treatment-related side effects. Osteonecrosis of the jaws (ONJ) is a known side effect of bisphosphonates and other anti-neoplastic drugs. This complication can lead to oncologic treatment interruptions as well as diminished quality of life. Most recommendations for treatment of ONJ are based on position papers and case reports, while evidence-based treatment paradigms are lacking. With cancer survivorship on the rise, long-term chemotherapeutic side effects are becoming more prevalent and attention to untoward oral complications cannot be understated. In this review, the accepted recommendations for dental clearance prior to head and neck chemo-radiation therapy are put forth as a means of possibly preventing and treating drug induced ONJ.

Sentinel node biopsy in lieu of neck dissection for staging oral cancer.

IMPORTANCE: Neck dissection is the standard staging procedure to ascertain the pathologic status of cervical lymph nodes in patients with oral cavity squamous cell carcinoma (OSCC), but it results in multiple morbidities. OBJECTIVE: To examine outcomes of patients with OSCC who underwent sentinel node biopsy (SNB) as the sole neck staging procedure. DESIGN: Retrospective review of patients who underwent SNB during the period 2005 through 2011. SETTING: National Cancer Institute­designated comprehensive cancer center. PARTICIPANTS: Thirty-eight patients with clinically T1 or T2N0 OSCC. INTERVENTIONS: Preoperative lymphoscintigraphy with intraoperative gamma probe localization was used. Sentinel lymph nodes were serially sectioned, formalin fixed, and examined at 3 levels. All patients with positive SNB results underwent neck dissection, and the patients with negative SNB results were observed clinically. MAIN OUTCOMES AND MEASURES: Sensitivity and predictive value of SNB, recurrence rates, and disease-specific survival rates. RESULTS: There were 18 T1 and 20 T2 tumors. Five patients had positive SNB results, of whom 3 had additional positive nodes on subsequent neck dissection. Two of 33 patients with negative SNB results developed a regional recurrence. The sensitivity and negative predictive value for staging the neck with SNB alone were 71% (5 of 7) and 94% (31 of 33), respectively. Mean follow-up was 31 months. The mean disease-free survival duration for patients with positive and negative SNB results was 30 and 65 months, respectively (P = .08). The disease-specific survival rate for patients with positive and negative SNB results was 80% and 91%, respectively. There was no significant difference in disease-specific survival between patients with true-negative and false-negative SNB results (34 vs 44 months; P = .38). CONCLUSIONS AND RELEVANCE: The majority of patients with positive results on SNB had additional positive nodes on neck dissection. A low rate of isolated neck recurrence was found in patients with negative results on SNB. Individuals with negative results on SNB exhibited better overall and disease-specific survival than those with positive results.

Lung cancer screening update.

Lung cancer is the leading cause of cancer-related mortality globally and the American cancer society estimates approximately 226,160 new cases and 160,340 deaths from lung cancer in the USA in the year 2012. The majority of lung cancers are diagnosed in the later stages which impacts the overall survival. The 5-year survival rate for pathological st age IA lung cancer is 73% but drops to only 13% for stage IV. Thus, early detection through screening and prevention are the keys to reduce the global burden of lung cancer. This article discusses the current state of lung cancer screening, including the results of the National Lung Cancer Screening Trial, the consideration of implementing computed tomography screening, and a brief overview of the role of bronchoscopy in early detection and potential biomarkers that may aid in the early diagnosis of lung cancer.