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Objective Radiation-induced xerostomia is one of the most common morbidities of radiation therapy in patients with head and neck cancer. However, in spite of its high rate of occurrence, there are few effective therapies available for its management. The aim of this study was to assess the efficacy of hyperbaric oxygen on the treatment of radiation-induced xerostomia and xerostomia-related quality of life. Study Design PubMed, Google Scholar, and the Cochrane Library were searched for retrospective or prospective trials assessing subjective xerostomia, objective xerostomia, or xerostomia-related quality of life. To be included, patients had to have received radiation therapy for head and neck cancer, but not hyperbaric oxygen therapy (HBOT). Results The systematic review initially identified 293 potential articles. Seven studies, comprising 246 patients, qualified for inclusion. Of the included studies, 6 of 7 were prospective in nature, and 1 was a retrospective study; and 2 of the 7 were controlled studies. Conclusions HBOT may have utility for treating radiation-induced xerostomia refractory to other therapies. Additionally, HBOT may induce long-term improvement in subjective assessments of xerostomia, whereas other therapies currently available only provide short-term relief. The strength of these conclusions is limited by the lack of randomized controlled clinical trials.

BACKGROUND Although stereotactic body radiation therapy (SBRT) is an established treatment option for early-stage lung cancer, there are no guidelines for reassessing patients for local treatment failure or intrathoracic recurrence after treatment. This study reports the sensitivity, specificity, and positive and negative predictive values for 18 F-fluorodeoxyglucose (FDG) PET-CT scanning when used to evaluate patients after SBRT. METHODS Charts were reviewed of all patients who received SBRT and a subsequent FDG PET-CT scan at a university hospital over a 5-year period. Pretreatment and 3-month posttreatment tumor characteristics on PET-CT scan and outcome data (adverse events from SBRT, need for repeat biopsy, rate of local treatment failure and recurrent disease, and all-cause mortality) were recorded. RESULTS Eighty-eight patients were included in the study. Fourteen percent of patients (12 of 88) had positive 3-month PET scans. Of the positive results, 67% (eight of 12) were true positives. Eighty-six percent (76 of 88 patients) had negative 3-month FDG PET-CT scans, with 89% (68 of 76) true negatives. FDG PET-CT scan performed 3 months after SBRT for non-small cell lung cancer (NSCLC) had a sensitivity of 50% (95% CI, 0.26-0.75), a specificity of 94% (95% CI, 0.89-1.0), a positive predictive value of 67% (95% CI, 0.4-0.93), and a negative predictive value of 89% (95% CI, 0.83- 0.96). CONCLUSIONS FDG PET-CT scan 3 months after treatment of NSCLC with SBRT was a specific but insensitive test for the detection of recurrence or treatment failure. Serial CT scans should be used for early surveillance following SBRT, whereas FDG PET-CT scans should be reserved to define suspected metastatic disease or to evaluate new abnormalities on CT scan, or for possible reassessment later in the follow-up period after radiation-related inflammation subsides.

Approximately 50% of head and neck cancer survivors experience dysphagia and related morbidity. Intensity-modulated radiation therapy (IMRT) is increasingly used to treat oropharyngeal cancers with excellent oncologic outcomes, but few studies have compared it with conventional 3-dimensional conformal radiation therapy (3D-CRT) to determine whether it can decrease treatment-related toxic and adverse effects.To determine whether IMRT improves percutaneous endoscopic gastrostomy (PEG) tube and treatment-related toxicity outcomes compared with 3D-CRT in patients with oropharyngeal squamous cell carcinoma.Retrospective review of 159 patients with oropharyngeal primary tumors with no history of chemotherapy, radiation therapy, or surgery of the head and neck who underwent definitive treatment with radiotherapy for oropharyngeal squamous cell carcinoma at the Hollings Cancer Center outpatient clinic, Medical University of South Carolina, from 2000 to 2009.Doses of 70 Gy in 35 daily fractions of radiotherapy delivered via IMRT or 3D-CRT.Primary end points included PEG tube dependence 1 year after radiotherapy start, weight loss during treatment, and change in Eastern Cooperative Oncology Group performance status. Secondary end points included overall and disease-free survival, disease recurrence, and toxic effect profiles.The IMRT group (n = 103) had a significantly lower rate of PEG tube dependence 1 year after treatment initiation than the 3D-CRT group (n = 56) for all patients (P = .02) and for those with advanced T stage (P = .01) and a shorter time to PEG tube removal (P .001). Acute grade 3 or greater toxic effects to skin and mucous membranes occurred less frequently in the IMRT group (P = .02 and P .001, respectively). The 2 groups did not differ significantly in weight loss, treatment failure (hazard ratio, 0.82 [95% CI, 0.47-1.41]), overall survival (P = .45), or disease-free survival (P = .26).The use of IMRT significantly improves PEG tube and toxicity-related outcomes compared with 3D-CRT in the treatment of oropharyngeal primary cancers. Given the association between mucosal toxic effects, PEG tube dependence, and dysphagia, these findings may be an indication of improved swallowing outcomes with IMRT.

Objectives:Radiation is an integral part of the treatment of head and neck cancer. However, side effects and toxicities are high and lead to dysphagia and dysphagia related morbidity in a significant proportion of patients. There has been interest in intensity modulated radiation therapy (IMRT) to decrease these side effects while preserving locoregional control and survival.Methods:We performed a retrospective review of patients who underwent definitive radiation for laryngeal squamous cell carcinoma (SCCa) at MUSC. Primary endpoints included: gastrostomy (PEG) tube dependence 1 year after radiation start, time to PEG tube removal, weight loss during treatment, Radiation Therapy Oncology Group (RTOG) toxicity profiles, disease-free survival, and overall survival.Results:Of 315 patients identified in the database, 74 had primaries of the larynx and underwent definitive radiation therapy. Twenty-four and 50 patients were treated with conventional radiation (3D-CRT) and IMRT respectively. Data analysis reve...

Salivary gland transfer (SGT) has the potential to prevent radiation-induced xerostomia. We attempt to analyze the efficacy of SGT in prevention of xerostomia and maintenance of salivary flow rates after radiation treatment (XRT). Systematic review and meta-analysis. Primary endpoint was efficacy of SGT in prevention of radiation-induced xerostomia. Secondary endpoint was change from baseline of unstimulated and stimulated salivary flow rates after XRT. Seven articles, accruing data from 12 institutions, met inclusion criteria. In a total of 177 patients at mean follow-up of 22.7months, SGT prevented radiation-induced xerostomia in 82.7% (95% CI, 76.6-87.7%) of patients. Twelve months after XRT, unstimulated and stimulated salivary flow rates rose to 88% and 76% of baseline values, respectively. In comparison to control subjects twelve months after XRT, SGT subjects' unstimulated (75% vs. 11%) and stimulated (86% vs. 8%) salivary flow rates were drastically higher in SGT patients. Salivary gland transfer appears to be highly effective in preventing the incidence of xerostomia in patients receiving definitive head and neck radiation therapy.

Purpose The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating epidermal growth factor receptor (EGFR) as a target. Erlotinib is a small-molecule inhibitor of EGFR. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy. Patients and Methods Patients with locally advanced SCCHN were randomly assigned to receive cisplatin 100 mg/m2 on days 1, 22, and 43 combined with 70 Gy of radiotherapy (arm A) or the same chemoradiotherapy with erlotinib 150 mg per day, starting 1 week before radiotherapy and continued to its completion (arm B). The primary end point was complete response rate (CRR), evaluated by central review. The secondary end point was progression-free survival (PFS). Available tumors were tested for p16 and EGFR by fluorescent in situ hybridization. Results Between December 2006 and October 2011, 204 patients were randomly assigned. Arms were well balanced for all patient characteristics including p16, with the exception of more women on arm A. Patients on arm B had more rash, but treatment arms did not differ regarding rates of other grade 3 or 4 toxicities. Arm A had a CRR of 40% and arm B had a CRR of 52% (P = .08) when evaluated by central review. With a median follow-up time of 26 months and 54 progression events, there was no difference in PFS (hazard ratio, 0.9; P = .71). Conclusion Erlotinib did not increase the toxicity of cisplatin and radiotherapy in patients with locally advanced HNSCC but failed to significantly increase CRR or PFS.

Radiation therapy has evolved into an integral modality in the treatment of non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). As technology has evolved, stereotactic body radiotherapy (SBRT) can now be used to achieve excellent local control in patients with early stage NSCLC who are non-operative candidates. Randomized trials are now comparing SBRT to surgery in early stage NSCLC. Chemoradiotherapy (CRT) is used as definitive therapy in the majority of cases of locally advanced NSCLC and can be used as neoadjuvant or adjuvant treatment to surgery in select cases. Most patients with SCLC will receive radiotherapy to the brain to treat brain metastases or prevent brain metastases, and patient with SCLC receive thoracic radiotherapy. In metastatic lung cancer, radiotherapy is used for palliation of brain metastases, spinal cord compression, superior vena cava syndrome, bony pain, hemoptysis, and airway obstruction. As treatment techniques continue to evolve, radiotherapy alone or in combination with new targeted therapies will continue to play an important role in the management of patients with lung cancer while reducing toxicity.

Purpose We report the results of a phase II study to determine the reproducibility of a submandibular salivary gland transfer (SGT) surgical technique for prevention of radiation (XRT)-induced xerostomia in a multi-institutional setting and to assess severity of xerostomia. Methods and Materials Eligible patients had surgery for primary, neck dissection, and SGT, followed by XRT, during which the transferred salivary gland was shielded. Intensity modulated radiation therapy, amifostine, and pilocarpine were not allowed, but postoperative chemotherapy was allowed. Each operation was reviewed by 2 reviewers and radiation by 1 reviewer. If 13 or more (of 43) were "not per protocol," then the technique would be considered not reproducible as per study design. The secondary endpoint was the rate of acute xerostomia, grade 2 or higher, and a rate of ≤51% was acceptable. Results Forty-four of the total 49 patients were analyzable: male (81.8%), oropharynx (63.6%), stage IV (61.4%), median age 56.5 years. SGT was "per protocol" or within acceptable variation in 34 patients (77.3%) and XRT in 79.5%. Nine patients (20.9%) developed grade 2 acute xerostomia; 2 had grade 0-1 xerostomia (4.7%) but started on amifostine/pilocarpine. Treatment for these 11 patients (25.6%) was considered a failure for the xerostomia endpoint. Thirteen patients died; median follow-up for 31 surviving patients was 2.9 years. Two-year overall and disease-free survival rates were 76.4% and 71.7%, respectively. Conclusions The technique of submandibular SGT is reproducible in a multicenter setting. Seventy-four percent of patients were prevented from XRT-induced acute xerostomia.

There is significant variation in recommendation for percutaneous endoscopic gastrostomy (PEG) tube placement in patients undergoing definitive chemoradiation therapy (CRT) for locally advanced squamous cell carcinoma of the head and neck (LAHNC), with some clinicians globally recommending prophylactic PEG and others waiting until toxicity has occurred. The present study was conceived to identify specific factors associated with PEG requirement, in a population of LAHNC patients who did not have up-front PEG placement.Using a quality assurance database, we identified patients with oropharyngeal (ORP) or laryngeal-hypopharyngeal (LHP) LAHNC who were treated with CRT for inclusion in a cohort study of factors impacting PEG placement. Eligibility included stage III/IV squamous cell carcinoma of ORP and LHP. Patients were excluded if they had a PEG placement prior to commencement of CRT. The primary endpoint compared across groups was PEG placement, and multivariate analysis of factors was performed.We identified 107 patients with LAHNC who did not receive PEG tubes prior to treatment. After treatment initiation, 41% of patients with ORP tumors required PEG placement during treatment compared with 16% of LHP patients (P = .03). After adjusting for covariates, multivariate analysis revealed that the only predictor for PEG placement was ORP primary (odds ratio 4.77; 95% confidence interval 1.6-13.8, P = .009) using LHP as reference.Our findings suggest that the patients with ORP cancers are more likely to require PEG placement during treatment and should be considered for prophylactic PEG placement, while LHP sites were associated with lower likelihood of PEG requirement. The primary reason for this difference appears to be severity of pharyngitis; proactive nutritional monitoring and supplementation should be implemented early. Patients with pretreatment risk stratification for PEG placement in LAHNC may improve quality of care and avoid unnecessary treatment breaks.

Background Temporal bone inverted papilloma (IP) is an extremely rare tumor. Its etiology is unknown and represents a source of debate. Only 2 previous cases of bilateral temporal bone IP have been reported. A case report and review of the literature via PubMed database search are presented. Mathods and Results A 52-year-old African-American man who initially underwent medial maxillectomy for right-sided nasal IP returned with bilateral temporal bone IP 7 months later without evidence of extension through the Eustachian tubes. Despite multiple resections and adjuvant radiation, the tumor transformed into squamous cell carcinoma and progressed to involve the intracranial dura, temporal lobe, and cervical dura. Conclusions Multiple origins may exist for temporal IP: direct extension, iatrogenic seeding, or development from ectopic Schneiderian epithelium. Temporal bone IP appears to represent a much more aggressive tumor than its nasal counterpart, necessitating aggressive early surgical intervention to decrease recurrence and transformation risk. © 2012 Wiley Periodicals, Inc. Head Neck, 2013

Background: Primary management of advanced head/neck cancers involves concurrent chemoradiotherapy . Subsequently, regional and local failures are managed with resection but there have been few reports that describe the morbidity and disease control outcomes of surgical salvage in this setting. Methods: Retrospective analysis describes complications, survival, and patterns of failure after salvage resection of isolated local and/or regional failures of head/neck cancer following definitive concurrent chemoradiotherapy. Results: Sixteen patients were identified for inclusion: laryngectomy in 11 patients, oral cavity/oropharynx resection in 2 patients, and neck dissection alone in 4 patients. Ten patients required graft tissue reconstruction (6 pedicle and 4 free flap). Median post-operative hospitalization was 7 days (range 3-19), and 4 patients required hospital re-admission. At a median survivor follow-up of 15.8 months (range 4.3-34.9), 10 patients were alive (6 without evidence of disease). Seven patients experienced disease recurrence at a median 6.7 months (range 0-12.6) following salvage resection (2 with isolated distant failures). Estimated 2-year local/regional control, freedom from failure, and overall survival were 58%, 39%, and 58%, respectively. Conclusions: Surgical salvage after primary definitive concurrent chemoradiotherapy is feasible with toxicity and outcomes similar to prior radiotherapy alone or sequential chemotherapy and radiation. Local andregional recurrence remains the predominant pattern of failure.

Background Esophageal strictures are a common sequela of chemoradiation and/or surgery to the head and neck cancers and can lead to stenosis and significant dysphagia. Endoscopic dilation endoscopic and placement of self-expanding stents are often to used relieve dysphagia symptoms. However, these stents are not without risks and complications. Methods We present a case of a 58-year-old man who had the rare complication of cervical osteomyelitis as a result of plastic esophageal stent placement for palliation of chemoradiation-induced strictures. Results The patient was successfully managed with immobilization of the cervical spine in a halo vest and appropriate antibiotics. Conclusion To the best of our knowledge, this is the first reported case of cervical spine osteomyelitis after self-expanding plastic stent (SEPS) placement for esophageal stricture. It was successfully treated with immobilization and antibiotic therapy. The treating physician should be aware of this rare complication to make an early diagnosis. Literature on esophageal stent-induced cervical osteomyelitis is reviewed. © 2012 Wiley Periodicals, Inc. Head Neck, 2012

Objective: Cisplatin-based chemoradiotherapy is standard treatment for locally advanced esophageal and gastroesophageal cancers; however, the optimal chemotherapy regimen remains to be defined. Methods: Retrospective single institution analysis of toxicities, response rates and survival outcomes in patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated with induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy. Secondary analysis for association of disease control and outcomes with demographic, tumor and treatment factors (including histology). Results: Fifty-three patients were eligible for the present analysis. All patients underwent endoscopic ultrasonography and were either cT3-4 and/or cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4 Gy, range 0‐61.2), and 35 patients completed four cycles of chemotherapy as planned (range 1‐4). Severe acute toxicities included Grade � 3 neutropenia and esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal) toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7‐63), 17 patients were alive (8 without disease) and 36 deceased. Forty patients experienced disease recurrence, with initial loco-regional, distant or both failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival and freedom from failure were 42 and 9%, respectively, without significant difference by histology. Conclusions: Cisplatin/irinotecan chemoradiotherapy is tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma esophageal cancers.

Major randomised trials have employed elective nodal irradiation as part of combined modality therapy for limited-stage small-cell lung cancer (SCLC). The present investigation describes patterns of failure, disease control, and survival outcomes for involved-field radiotherapy with concurrent chemotherapy, without elective irradiation of uninvolved mediastinal nodal regions.Retrospective analysis of SCLC patients treated with curative-intent accelerated, twice-daily radiotherapy and concurrent platinum-based chemotherapy at an academic institution. Treatment fields were reviewed, and patients who completed ≥42 Gy in 1.5 Gy twice-daily fractions to involved fields (without elective irradiation of uninvolved mediastinal lymphatic regions) were included in the present analysis. Initial patterns of failure, disease control and overall survival were recorded.Fifty-two patients fulfilled study criteria and were included in the present analysis. All but one patient completed three to four cycles of chemotherapy, and 10 patients experienced grade 3 acute esophagitis. At a median survivor follow-up of 35 months (range 5.5-91.9), 22 patients were alive (15 without recurrence) and 30 had died (23 of/with disease, four of unknown cause, two of other cause and one of treatment toxicity). Initial site(s) of disease failure were loco-regional only (11 patients), distant only (14) and loco-regional plus distant (3). There were no cases of isolated out-of-field mediastinal recurrence in the absence of supraclavicular or more distant disease. The estimated 3-year disease-free and overall survivals were 36% and 44%, respectively.Involved-field radiotherapy did not appear to have an adverse impact on the anticipated patterns of failure, disease control, or overall survival in this population of limited-stage SCLC patients.

The optimal concurrent chemoradiotherapy regimen for definitive treatment of locoregionally advanced head and neck cancer remains to be determined. The present investigation reports toxicities, disease control, patterns of failure, and survival outcomes in a large mature cohort of patients treated with low-dose weekly platinum-based concurrent chemoradiotherapy.Retrospective single-institution series.Toxicity and outcome data for locoregionally advanced head and neck cancer patients treated with low-dose weekly platinum-based chemotherapy concurrent with standard fractionation radiotherapy were retrospectively collected and analyzed from a clinical database. Survival analysis methods, including Kaplan-Meier estimation and competing risks analysis, were used to assess locoregional disease control, freedom from failure, and overall survival.Ninety-six patients were eligible for the present analysis. Nearly all patients had American Joint Committee on Cancer clinical stage III to IVB disease (99%). Severe acute toxicities included grade 3 mucositis (61%), grade 3/4 nausea (27%/1%), and grade 3 neutropenia (8%). Thirty-seven patients (38%) required hospitalization for a median of 7 days (range, 1-121). Ninety-two percent of patients completed the fully prescribed course of radiotherapy, and 87% completedor=6 cycles of chemotherapy. At a median survivor follow-up of 40 months (range, 8-68), 47% of patients were without evidence of disease recurrence. The estimated 4-year freedom from failure and overall survival were 48% and 58%, respectively. Initial site(s) of disease failure were locoregional for 22 patients, locoregional and distant (five patients), and distant only (14 patients).Weekly low-dose platinum-based chemotherapy with full-dose daily radiotherapy is a tolerable alternative regimen for locoregionally advanced head and neck cancers, with comparable efficacy and patterns of failure to alternative regimens.

The aim of this study was to compare toxicities, disease control, survival outcomes, and patterns of failure between groups of limited-stage small-cell lung cancer patients treated with once-daily versus twice-daily radiotherapy and concurrent chemotherapy.This single-institution retrospective analysis included a comparison of two of radiotherapy regimens to planned doses of (1)or =59.4 Gy at 1.8-2.0 Gy per once-daily fraction or (2)or =45 Gy at 1.5 Gy per twice-daily fractions with concurrent platinum-based chemotherapy. Comparative analyses of toxicities and disease control were performed.A total of 71 patients were included in the present study (17 once-daily, 54 twice-daily). Patient, tumor, staging, and treatment factors were similar between the two treatment groups. Median planned radiotherapy doses were 60 Gy (range 59.4-70.0 Gy) and 45 Gy (range 45-51 Gy) for the once-daily and twice-daily groups, respectively. Acute toxicities were similar between the groups ( approximately 20% grade 3 esophagitis). At a median survival follow-up of 26.2 months (range 3.4-85.5 months), 42 patients had died. The 2-year overall survival estimates were similar at 43% and 49% for the once-daily versus twice-daily groups, respectively. Isolated in-field failures were similar between the two groups ( approximately 17%).The present analysis did not detect a statistically significant difference in acute toxicities, disease control, or survival outcomes in limited-stage small-cell lung cancer patients treated with concurrent chemotherapy and once-daily versus twice-daily radiotherapy.

Purpose We used computed tomography (CT) perfusion to evaluate the acute and late effect of radiation therapy (RT) on spinal cord (SC) hemodynamics in patients without symptoms of myelopathy. We hypothesized that SC perfusion could be acutely altered during RT. Methods and Materials We analyzed neck CT perfusion studies of 36 head-and-neck cancer patients (N1), 16 of whom had previously undergone RT. In a separate group of 6 patients (N2), CT perfusion studies were obtained before RT, after 40 Gy, and after treatment completion. Results In the N1 group, SC blood flow (BF), blood volume (BV), mean transit time (MTT), and capillary permeability (CP) maps were not significantly different between RT-treated and RT-naive patients. In the N2 group, BF and CP were significantly increased during treatment compared with the baseline and post-RT studies. Conclusions Radiation therapy of the head and neck may cause transient perturbations of SC perfusion that seem to reverse after treatment. There are no definite chronic effects of RT on SC perfusion observeable at the typical doses administered during treatment of head and neck malignancies.

Objective: To investigate the association between initial body mass index (BMI) and chemoradiation therapy (CRT) outcomes in head and neck cancer patients. Methods: Retrospective study of 72 patients with American Joint Committee on Cancer stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, or larynx treated with primary concurrent CRT with curative intent over a 5 year period. Logistic and Cox regression analyses were used to determine the association between initial BMI and percutaneous endoscopic gastrostomy tube dependence, tumor recurrence, disease-free survival, and overall survival while controlling for the independent variables of age, sex, race, site, stage, and smoking and alcohol use. Results: Patients with normal or low BMI (BMI ≤25 kg/m2) were significantly more likely to be percutaneous endoscopic gastrostomy dependent at last follow-up (odds ratio 4.13; 95% confidence interval [CI] 1.3–12.9; P = .014). This group also had significantly earlier recurrence (hazard ratio 4.4; 95% CI 1.2–15.9; P = .026) and shorter overall survival (hazard ratio 3.6; 95% CI 1.04–12.6, P = .043). Conclusions: The present study suggests that CRT patients with BMI greater than 25 have improved swallowing outcomes, longer time to disease recurrence, and improved survival when compared with similar patients with lower BMI. BMI at presentation may be an important clinical factor to consider when determining the optimal treatment modality for a head and neck cancer patient. Further investigation is required to determine whether primary surgery should be the preferred treatment in normal or low BMI patients.

Turnarounds are like exciting thrillers which describe dramatic recovery of declining organizations. Since such recoveries have great relevance for the economic development particularly of developing countries facing resource scarcity, researchers with increasing interest have enriched the turnaround literature, especially in the last four decades. Research has highlighted many facets of turnaround. These include turnaround actions, strategies, types, elements, stages etc. Though the research covers largely the private sector entities, but effort, though little, is not nonexistent for the public sector. The paper examines a large complex departmental commercial organization of the Government of India and its much-talked about turnaround in the theoretical perspective of stage theory. The paper not only fills up the gap of research in public sector but also uses the established stage theory model to answer the question of sustainability of the Indian Railways turnaround. The analysis goes back to the theoretical propositions which are by and large supported by the analysis of the turnaround of the Indian Railways.

Retrospective analysis of patients with medically inoperable non-small cell lung cancer treated with continuous high-dose external beam radiation therapy at the Medical University of South Carolina.We identified 35 patients with non-small cell lung cancer treated 1998-2002. None were candidates for resection for reasons including: pulmonary function (n = 23), previous cancer (n = 9), other co-morbidities (n = 2), and refusal of surgery (n = 1). Median percent predicted forced expiratory volume in 1 second was 41.5%. Median age was 71 years. Five patients had more than one primary tumor: three were concurrently treated, two were sequentially treated. Lesion sizes were3 cm (n = 24); 3-5 cm (n = 12), and5 cm (n = 5). Nodal stage was as follows: N0 (n = 33) and N1 (n = 2). Radiation therapy was administered once daily: median dose was 80.5 Gy/35 fx/2.3 Gy/fx. The clinical target volume was tumor plus nodesor =1.0 cm. V20 data were available for 12 patients, with a mean value of 15.7%.Thirty-four patients completed treatment. Median follow-up was 23.0 months. There were 26 deaths: 19 died from non-small cell lung (73%) and seven died from co-morbid illness (27%). Median survival was 24 months (95% CI, 18.0-31.9 months). Four patients were alive with disease, and five were alive disease-free at 10- and 68-month follow-ups. Of 41 lesions, local failure occurred in 15 lesions (37%) of which 3 local failure patients (9%) failed concomitantly in untreated regional lymph nodes. There were no isolated nodal recurrences. Distant progression: 10 patients (29%) of which 6 distant progression without local failure. Two patients who both had prior lobectomies experienced grade 5 toxicities.Continuous high-dose external beam radiation therapy 80.5 Gy administered in 35 fractions was tolerated. Treatment-related death was rare (6%) and isolated to patients with prior lobectomies in an extremely high-risk population. Most mortality was lung cancer-related. The dose of 80.5 Gy in 7 weeks is supported for patients with single lesions and no prior lobectomy. Local failure dominates and higher effective doses should be explored.

Thyroid cancer is an uncommon malignancy that accounts for roughly 1% of all new cancers. Although anaplastic lesions constitute fewer than 5% of thyroid cancers, they represent over half of thyroid cancer-related deaths. The relative rarity of anaplastic thyroid cancer, its aggressive nature, and its rapidly fatal course have contributed to the difficulty in developing effective treatment for this disease. Radiation, chemotherapy, and surgery are rarely curative, but combinations of these modalities appear to offer greater benefit than any single treatment. New treatment modalities are desperately required, and promising molecular-based therapies are being investigated.

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Objectives: Primary aim of the ongoing study ([NCT01898091][1]) is to determine whether a mouthrinse containing extract of neem leaf (Azadirachta indica A. Juss.), a tropical evergreen tree with anti-inflammatory and anti-microbial medicinal properties, will lessen the severity of oral mucositis (OM) in patients undergoing radiation therapy (RT) to the head and neck. Secondary aims are to assess the effects of the neem mouthrinse on the microbial environment of the oral cavity and on quality of life. Methods: Design is a double-blind, controlled, randomized, parallel-group Phase II clinical trial at a single NCI designated center. Block-randomization was used for patient assignment, stratified by tobacco use. Eligibles were adults with histologically confirmed head and neck cancer (HNC) whose treatment includes RT for 7 weeks. HNC includes malignancy of the oral cavity, oro-pharynx and larynx (ICD-9 codes 140 - 149, 161; ICD-O morphology code of 2 or 3). Exclusion criteria include prior HNC radiotherapy, baseline mouth and throat soreness (MTS) score of >3, ECOG performance status >2, allergy or inability to use mouthrinse, and language barrier. Evaluable participants receive > 40 Gy RT and participate to week 6 RT. Study duration is 12 weeks with visits at baseline, weekly during RT, 3 telephone visits post RT, and one-month follow-up visit. Data were collected using the Oral Mucositis Daily Questionnaire, Functional Assessment of Cancer Therapy-Head and Neck, and Symptom Distress Scale questionnaires; CariScreen for oral microbial load, and ELISA and flow cytometry for salivary analyte measures. Results: Of 53 patients enrolled, 3 screen failed and 8 withdrew leaving 42 with evaluable data. Neem (n = 23) and placebo (n = 19) groups were not statistically different for demographic and clinical variables. Major hypothesis assessed as the maximum change in MTS score from baseline during 6 weeks of RT resulted in a larger change, 1.91 with SD 1.34 for neem group vs. 1.71 with SD 1.29 for placebo group based on a Wilcoxon rank sum test with one-sided alpha = 0.05. Preliminary results suggest no difference in the maximum change in severity from baseline (p = 0.85). Neem group had higher adherence to mouthrinse protocol measured as ≥4 days mouthrinse use per week for six weeks (OR 2.56, p = 0.19). Additional outcomes of ongoing comparisons across groups include time to maximum OM severity, time to onset of OM, percent of patients with MTS scores

To determine whether laryngeal penetration and aspiration in oropharyngeal cancer survivors differ by treatment group.Cross-sectional study of patients with stage III or IV oropharyngeal squamous cell carcinoma who were at least 12 months removed from combined modality therapy and clinically free of disease.Potential subjects were stratified by tumor site and tumor T stage to achieve a similar comparison between chemoradiotherapy (n = 10) and surgery/radiotherapy (n = 11) groups. Validated instruments used to evaluate swallowing included the Penetration-Aspiration Scale and the M. D. Anderson Dysphagia Inventory.Patients with oropharyngeal cancer treated with chemoradiotherapy demonstrated greater airway protection according to Penetration-Aspiration Scale scores than those treated with surgery and radiotherapy on 5-mL (P = .02), 10-mL (P = .04), and 20-mL (P = .04) liquid barium swallows. Also, the oropharyngeal chemoradiotherapy group had better self-perceived swallowing ability than the surgery-radiotherapy group on the basis of the M. D. Anderson Dysphagia Inventory (P = .02).The present study suggests that patients with oropharyngeal cancer who successfully complete chemoradiotherapy protocols without surgical salvage retain greater airway protection during swallowing and better swallowing-related quality of life than patients treated with primary surgery and radiotherapy.

Purpose Assess and compare the accuracy of the current AJCC TNM staging system among a large population-based cohort with squamous cell carcinoma (SCC) of the base of tongue (BOT)/tonsil and other oropharyngeal (OP) subsites. Materials and methods Patients with OP SCC were identified using the Surveillance Epidemiology and End Results (SEER) database. Patients were classified according to the 6th edition AJCC TNM system, and also by primary site as follows: (1) BOT/tonsil ( n = 14,151), and (2) other oropharynx ( n = 1437). The Kaplan–Meier method was used to estimate 5-year disease-specific survival (DSS) in each AJCC TNM classification group. Analyses were then stratified according to primary site subgroups. Results Patients with BOT/tonsil tumors were more likely to be younger white males with higher N-stage and overall-stage tumors ( p Fig. 1 ). Although DSS was well-discriminated according to T and M classifications, discrimination according to N classification was poor and disconcordant between the two primary site subgroups. Overall (not shown), and in the BOT/tonsil group, N2a patients had significantly better DSS vs. those with N0/N1 disease ( Fig. 2 ). Conclusion The current AJCC classification system may need to be modified for BOT/tonsil tumors, especially regarding N stage. Unilateral nodal metastasis does not appear to uniformly denote a poor prognosis in OP SCC.

Thyroid cancer is an uncommon tumor accounting for roughly 1% of all new malignancies. Differentiated (ie, papillary or follicular) thyroid carcinoma is usually asymptomatic, and frequently appears as a solitary thyroid nodule but few show cervical lymphadenopathy or metastasis to lung, bone, or liver. Fine needle aspiration (FNA) is recommended in the initial diagnostic test. Depending on the size of the lesion and other associated risk factors, most patients are treated with total or near total thyroidectomy. Postoperative radioiodine ablation is performed when tumor has a potential for recurrence. Recurrence rates and cancer-specific mortality is decreased by suppressing thyroid stimulating hormone (TSH). Long-term surveillance and follow-up with physical examination every 3 to 6 months for 2 years and then annually if patient remains cancer free. Whole body iodine scans are done every 12 months for follow-up until one negative scan (either withdrawal of thyroid hormone or rhodium complex -TSH). Thyroglobulin measurements (with antithyroglobulin antibodies) and ultrasound neck are suggested at 6 and 12 months and then annually if disease free.

Malignancies of the nasal cavity and paranasal sinuses represent a wide spectrum of histologies, tissues of origin, and anatomic primary sites. The inherent difficulty in generalizing treatment approaches is obvious, given the numerous variables associated with the broadly-based term, paranasal sinus malignancy (PNSCa). Nevertheless, the majority of epithelial and salivary malignancies of this region (ie, squamous cell carcinoma, adenocarcinoma, adenoid cystic carcinoma, sinonasal undifferentiated carcinoma, and esthesioneuroblastoma) require surgical intervention as part of any treatment regimen. Recent trends have broadened the indications for chemotherapeutic and radiotherapeutic options in the management of advanced PNSCa. Nonepithelial malignancies, including the wide variety of sarcomas arising in this region, most commonly require multimodality treatment including chemotherapy, radiation, and/or surgery for definitive treatment. Moreover, the proximity of the nasal cavity and paranasal sinuses to structures including the orbit, dura, brain, cranial nerves, and carotid arteries mandates careful radiologic and neurologic evaluations throughout the course of the disease. Surgical advances now permit complex tumor removal and reconstruction surrounding these structures resulting in functional and cosmetic improvements when compared to earlier techniques. However, additional clinical trials are necessary to systematically evaluate the locoregional control, organ-preservation strategies, and survival related to the variety of treatments currently available.

Treatment and cure of salivary gland neoplasms requires surgical intervention in most cases. For parotid neoplasms, the most common surgical procedure performed is the superficial parotidectomy with facial nerve preservation. Postoperative radiation therapy is indicated in high-grade salivary gland malignancies and malignancies with increased risk of locoregional recurrence. Primary radiation, including neutron beam techniques, may play a role in certain histologic types or nonoperative candidates. Chemotherapy has yet to result in improvements in survival or quality of life in the treatment of salivary gland malignancy. Advances in radiation therapy techniques, including intensity-modulated radiation therapy, provide opportunities for reduced morbidity.

Oral cancer is the sixth most common cancer in the world, and it continues to represent a serious public health problem. Oral cancer is a preventable disease, related to behavioral and lifestyle factors, including tobacco and alcohol. Prevention and early detection of oral cancer remain the goals of national efforts to reduce the impact of this disease on the public. Surgical treatment is the mainstay of therapy for patients with oral cancer, particularly in advanced stages of cancer. External beam radiation therapy and brachytherapy have been used successfully as the primary modality for treating patients with early stage oral cancer, and they are the standard of care for use as adjuvant therapy in postoperative cases of patients with advanced stage oral cancer. There is an emerging trend for the use of chemotherapy in combination with radiation therapy and surgery for patients with advanced, recurrent, and metastatic head and neck cancer, although evidence is limited regarding survival benefit when used for treating patients with oral cavity carcinoma. Any report on the treatment of oral cancer is incomplete without consideration of functional and aesthetic outcomes, particularly addressing speech, swallowing, masticatory efficiency, and dental rehabilitation. Future generations will continue to fight these dreadful diseases until scientists and clinicians are provided the opportunities to expand efforts to prevent, detect (early), and eradicate oral and other head and neck cancers.

5503 Background: The combination of cisplatin and radiotherapy is a standard treatment for patients with locally advanced SCCHN. Cetuximab-radiotherapy is superior to radiotherapy alone in this population, validating EGFR as a target. Erlotinib, a small molecule inhibitor of EGFR, has activity in recurrent/metastatic disease. Adding EGFR inhibition to standard cisplatin-radiotherapy may improve efficacy. Methods: Patients with locally advanced SCCHN were randomized to receive cisplatin 100mg/m2 on days 1,22 and 43 combined with 70Gy of radiotherapy (arm A) or the same chemoradiotherapy combined with erlotinib 150mg/day, starting one week prior to radiotherapy and continued to its completion (arm B). Randomizing 204 patients had 80% power to compare a 60% complete response rate (CRR) to a 40% null rate. Available tumors were tested for p16, ERCC1 and EGFR FISH. Results: Between June 2006 and October 2011, 204 patients were randomized. Results presented are based on intention to treat. There were more females on arm A however no other differences in patient characteristics, including p16 positivity. Patients on arm B had more rash and gastrointestinal adverse events, but treatment arms did not differ for rates of other grade III/IV toxicities or serious adverse events (SAEs). Arm A had a CRR of 61% and arm B had a CRR of 68% (p=0.3). With a median follow-up of 23 months, there were only 29 events in the overall survival analysis and 46 in the progression-free survival (PFS) analysis. The 2 and 3 year PFS were 71% and 63% for arm A and 78% and 73% for arm B (p=0.61). Conclusions: The addition of erlotinib did not increase the rate of SAEs but failed to significantly increase CRR. As seen in other recent trials, our results in both arms are superior to historical comparisons. Updated PFS data will be presented. Supported by a grant from the investigator-initiated trial program of Genentech/OSI.

5580 Background: Cisplatin and radiotherapy is a standard therapy for patients with SCCAHN. Targeting the EGFR pathway in combination with radiotherapy improves survival over radiotherapy alone. Er...

OBJECTIVE: To investigate actual driving performance in a group of patients with cancer in the head and neck region. DESIGN: A nonrandomized controlled trial. PARTICIPANTS: Ten patients with cancer in the head and neck region participated in a driving evaluation using a virtual reality driving simulator. Driving performance from the simulator and observer ratings on participants' driving behaviors were compared between a group of patients with cancer in the head and neck region and a group of 50 community control subjects. MAIN OUTCOME MEASURES: Average speed, mean brake reaction time, steering variability, the total number of (fatal and nonfatal) collisions during the 12-minute evaluation course on the driving simulator, and the score of the 18-item Simulator Driving Performance Scale. RESULTS: Using Mann-Whitney U tests, the brake reaction time and the steering variability in the cancer group were significantly longer and larger, respectively, than those in the control group (P = .04) and (P = .02). However, no significant differences were found between the 2 groups in the mean rank scores for average speed, total number of collisions, and Simulator Driving Performance Scale (P >.05 for all). CONCLUSIONS: This pilot study provides preliminary evidence indicating inferior driving performance in a group of patients with cancer in the head and neck region when compared with a community control group. Further study is needed to investigate factors attributing to the difference. Language: en

5578 Background: Locally recurrent disease (RD) contributes to the majority of SCCHN-related deaths. In addition, second primary tumors (SPT) develop in approximately 30% of patients (pts) who were cured of their primary malignancy. For pts with disease (RD or SPT) in a previously irradiated region, therapeutic options are limited. Approaches utilizing reirradiation with concurrent chemotherapy (CT) have been investigated, with promising initial results. We retrospectively report the clinical outcome & toxicity of such a regimen. Methods: A cohort of pts with locally recurrent or second primary SCCHN within previous radiation portals were treated with concurrent chemoradiotherapy (CRT). Pts received HFx RT (1.5 Gy/Fx BID × 5 every 2 wks × 4), in combination with DDP 15 mg/m2 IV QD × 5 and P 20 mg/m2 IV QD × 5 q 2 wks × 4. Filgrastim was given on days 6–13 of each 2 wk cycle. Results: Nineteen pts were treated (median age 61; 84% with RD at median of 22 mos, 16% SPT; primary site: oropharynx-32%, larynx-32%, oral cavity 21%). Two pts had treatment discontinued early (due to hemoptysis & declining performance status, respectively). Seventeen pts were evaluable at a median f/u of 13 mos. Acute skin & mucous membrane toxicity (Grade ≥ 2) was seen in 11% and 5% of pt’s, respectively, and 32% of pts developed skin fibrosis as a late radiation toxicity. Most pts (82%) received all 4 scheduled cycles of CT. Grade ≥ 3 hematologic toxicity occurred in 29% of pts (anemia 24%, neutropenia 24%, & thrombocytopenia 12%). Infection was the primary non-hematologic toxicity, with Grade ≥ 3 infection in 29% (4 pneumonia, 1 vascular catheter). There was 1 treatment-related death (hypotension with CVA). Of the 16 pts who completed treatment, 4 had initial surgery, and thus had no measurable disease upon commencing CRT. Objective responses to CRT were noted in all of the remaining 12 pts and 50% achieved a CR. One-year OS rate was 65%, with median survival not yet reached. Conclusions: RD and SPT pts who are not surgical candidates have limited treatment options. Aggressive reirradiation with biweekly CT produces excellent response rates, with acceptable local and systemic toxicities. No significant financial relationships to disclose.