Characterizing Lymph Node Burden With Elective Unilateral Neck Irradiation in Human Papillomavirus-Positive Tonsil Squamous Cell Carcinoma: Defining the Upper Limits.

Objectives Elective unilateral neck irradiation in well-lateralized tonsil carcinoma for N2b disease is controversial. Metrics regarding nodal burden beyond the N-stage to define the upper limit of this de-escalation approach remain limited. We investigated the role of nodal number, level, and volume on outcomes in patients with well-lateralized tonsil carcinoma treated with this approach. Methods A total of 37 patients received radiotherapy (RT) with unilateral neck coverage for well-lateralized tonsil cancer. Of patients, 95% had p16+ disease, and 81% were staged with positron emission tomography/computed tomography. The majority of patients received definitive chemoradiation on prospective de-escalation trials. Ten patients had ipsilateral neck dissections and were treated adjuvantly. The median RT dose to the ipsilateral neck (generally II-IV) was 45 Gy. The effects of nodal number, max dimension, volume, and level on recurrence-free survival (RFS) and overall survival (OS) were to be analyzed via Cox proportional hazards (Cox-PH). Results After a median follow-up of 3.9 years, two-year RFS and two-year OS were 100% and 97%, respectively. Given the 0% contralateral recurrence rate, Cox-PH analysis was not performed. Of patients, 70% were American Joint Committee on Cancer (AJCC) 7th edition N2b, with a median number of nodes, number of nodal levels, max dimension, and volume of two, one, 3.4 cm, and 15.6 cc, respectively. There were several patients with low-lying nodes; aggregate nodal volume measured was up to 85.4 cc. Conclusion Unilateral neck irradiation in well-lateralized tonsil carcinoma resulted in no contralateral recurrence. Nodal volume, level, and number do not seem to have a significant impact on outcomes.

Phase I study of nab-paclitaxel-based induction followed by nab-paclitaxel-based concurrent chemotherapy and re-irradiation in previously treated head and neck squamous cell carcinoma.

BACKGROUND: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC. METHODS: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX). RESULTS: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2. CONCLUSIONS: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation. CLINICAL TRIAL INFORMATION: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326.

Adjuvant treatment for high-risk salivary gland malignancies and prognostic stratification based on a 20-year single institution experience.

BACKGROUND AND AIM: Retrospective analysis of the utility of adjuvant radiation (RT) or chemoradiation (CRT) and identify prognostic features for patients with high-risk head and neck salivary gland cancers. METHODS: From 1/1997 to 12/2017, 108 patients underwent surgery, and RT (n = 50) or CRT (n = 58) for positive lymph node(s), extracapsular extension, perineural invasion, lymphovascular space invasion, positive/close margin, and/or grade 3 disease. Outcomes were estimated with the Kaplan-Meier method. Significant predictors identified through regression analyses were incorporated into multivariable regression (MVA). Toxicities were compared using chi-square. RESULTS: The median follow-up was 52 months (range: 3-226). The number of risk factors (RFs) between RT and CRT groups were: 0 to 1 (44% vs 7%), 2 to 3 (48% vs 41%), or 4 to 6 (8% vs 52%), respectively (P < .01). On MVA, stage 3 or 4 disease predicted worse outcomes including overall survival (HR 4.55, P = .01). Increasing number of RFs predicted worse disease-free survival, distant metastasis-free survival, and overall survival (2-3 RFs: HR 3.38, P = .03; 4-6 RFs: HR 5.78, P < .01), but not locoregional control (P = .54). So, adjuvant CRT may have provided comparable locoregional control for patients with more adverse features, but the CRT did not translate into improved distant control. There was no difference in acute or late grade 3+ toxicities, or parenteral nutrition (P = .98, P = .85, and P = .83), respectively. CONCLUSIONS: Adjuvant CRT provides adequate locoregional control in patients with more adverse RFs. The absolute number of RFs serves prognostic significance and should be considered in future prospective trials.

Baseline Computed Tomography Radiomic and Genomic Assessment of Head and Neck Squamous Cell Carcinoma.

PURPOSE: To determine the relationship between computed tomography (CT) radiomic features and gene expression levels in head and neck squamous cell carcinoma (HNSCC). METHODS: This retrospective study included 66 patients with HNSCC primary lesions (36 oropharyngeal, 6 hypopharyngeal, 10 laryngeal, 14 oral cavity). Gene expression information for 6 targetable genes (fibroblast growth factor receptor [FGFR]1, epidermal growth factor receptor [EGFR], FGFR2, FGFR3, EPHA2, PIK3CA) was obtained via Agilent microarrays from samples collected between 1997 and 2010. Pretreatment contrast-enhanced soft tissue neck CT scans were reviewed, and 142 radiomics features were derived. R was used to calculate Pearson correlation coefficients were calculated between gene expression levels and each radiomic feature. P values were adjusted using the false discovery rate (FDR) method. RESULTS: There were significant correlations between FGFR1 and 5 gray level cooccurrence matrix (GLCM) features with FDR-adjusted P values less than 0.05: inertia (r = 0.366, FDR-adjusted P = 0.006), absolute value (r = 0.31, FDR-adjusted P = 0.024), contrast (r = 0.366, FDR-adjusted P = 0.006), difference average (r = 0.31, FDR-adjusted P = 0.024), and difference variance (r = 0.37, FDR-adjusted P = 0.005). There was 1 correlated feature for FGFR2 with an FDR-adjusted P value less than 0.05: fractal dimension box-coarse (r = 0.33, FDR-adjusted P = 0.018). There was 1 correlated feature for EPHA2 with an FDR-adjusted P value less than 0.05: GLCM entropy (r = -0.28, FDR-adjusted P = 0.049). Six of the 7 features that showed significant correlation belonged to the GLCM class of features. CONCLUSIONS: The CT radiomic features demonstrate correlations with FGFR1 status in HNSCC and should be further investigated for their potential to predict FGFR1 status.

Is It Worth It? Consequences of Definitive Head and Neck Reirradiation.

Locally recurrent head and neck malignancies after definitive radiation or chemoradiation represent challenging clinical scenarios requiring careful consideration of individualized risks and benefits before deciding upon the next best course of therapy. Herein, a case-based approach to personalized decision making highlights the expert opinions of leaders in head and neck oncology. Topics of interest include optimal candidacy for reirradiation or salvage surgical resection, the judicious use of chemotherapy as induction therapy or as a radiosensitizing agent, the incorporation of immunotherapy into the treatment paradigm for locally recurrent disease, and the impact of various treatment modalities on quality of life and functional outcomes. Interestingly, the lack of consensus among the experts on topics as fundamental as the appropriateness of offering reirradiation at all and as nuanced as target volume delineation for the reirradiated field suggests that there is no straightforward approach in this scenario. Common to all opinions is a desire to maximize the therapeutic ratio for a patient potentially facing a grim prognosis, and honest discussions about goals of care and expectations for post-treatment quality of life should be central to the clinical approach to this and similar cases.

Dose and Volume De-Escalation for Human Papillomavirus-Positive Oropharyngeal Cancer is Associated with Favorable Posttreatment Functional Outcomes.

PURPOSE: To report functional outcomes for patients with human papillomavirus-positive oropharyngeal cancer treated on a phase 2 protocol of risk- and induction chemotherapy response-adapted dose and volume de-escalated radiation therapy (RT)/chemoradiation (CRT). METHODS AND MATERIALS: Patients were stratified as low risk (LR) or high risk (HR) according to T/N-stage and smoking history. Induction chemotherapy was followed by radiographic response assessment. LR patients with ≥50% response received 50 Gy RT (RT50), whereas LR patients with 30% to 50% response or HR patients with ≥50% response received 45 Gy CRT (CRT45). All other patients received 75 Gy CRT (CRT75) with RT limited to the first echelon of uninvolved nodes. Pre- and post-RT/CRT modified barium swallow studies were performed. Percutaneous endoscopic gastrostomy (PEG) tube placement, body mass index (BMI), and narcotic use were recorded. Statistical comparisons used linear or logistic regression, the Mann-Whitney U test, the χ2 test, or Fisher's exact test as appropriate. RESULTS: Twenty-eight LR and 34 HR patients were enrolled; 49 completed RT50/CRT45 and 11 completed CRT75. PEG-tube dependency at the end of RT/CRT and 3 months post-RT/CRT significantly differed according to risk and treatment groups (all P < .05). Treatment intensity was independently associated with 3-month PEG status while adjusting for risk group (P = .002). The CRT75 group had a median -8.42% change from baseline BMI at 1 year post-RT/CRT versus -2.54% for the RT50/CRT45 group (P = .01). At the end of RT/CRT, CRT75 patients were less likely to tolerate a normal diet, more likely to have swallowing performance status scale scores ≥4, more likely to have Rosenbek's penetration-aspiration scores ≥7, more likely to have developed trismus, and more likely to require narcotics >2 months (all P < .05). CONCLUSIONS: Induction chemotherapy followed by risk- and response-adapted dose and volume de-escalated RT/CRT is associated with clinically meaningful functional outcomes including (1) improved swallowing function, (2) higher BMI, and (3) shorter narcotic use for patients receiving de-escalation.

Prognostic value of pre-treatment CT texture analysis in combination with change in size of the primary tumor in response to induction chemotherapy for HPV-positive oropharyngeal squamous cell carcinoma.

BACKGROUND: To determine the additive value of quantitative radiomic texture features in predicting progression in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) based on pre-treatment CT. METHODS: Retrospective analysis of a single-center cohort of adult patients enrolled in a response-adapted radiation volume de-escalation trial treated with induction chemotherapy. Texture analysis of HPV-positive OPSCC was performed via primary tumor site contouring on pre-treatment contrast-enhanced CT scans. Percent change in size of the tumor in response to induction chemotherapy based on RECIST 1.1 criteria and progression free survival were clinically determined for this cohort. Receiver operating characteristic (ROC) analysis was performed to compare the accuracy of percent change in tumor size after induction chemotherapy with a combination of change in tumor size and radiomic texture features for predicting tumor progression. RESULTS: Radiomic texture analysis of the primary tumors in 38 patients with OPSCC depicted on pre-treatment neck CT scans using skewness and entropy in combination with percent change in tumor size after induction chemotherapy yielded a statistically significant increase in accuracy for predicting tumor progression over change in tumor size alone, with an area under the curve of 0.80 versus 0.56 (one-tailed P=0.0087). CONCLUSIONS: This pilot study suggests that disease progression in patients with HPV-positive OPSCC is more accurately predicted using a combination of texture features on pre-treatment CT scans, along with change in tumor size compared to change in tumor size alone and could therefore serve as a radiomic texture signature.

Management of Early Head and Neck Cancer in Elderly Patients.

Head and neck squamous cell carcinoma (HNSCC) frequently affects elderly patients. Given the frailty and comorbid conditions of this population as well as the potential toxicities associated with treatment, there is a risk of undertreatment in older patients. However, there is growing evidence that benefit with standard treatment is similar in the elderly and in younger patients. Few prospective trials specifically target the elderly, which forces clinicians to rely on subgroup analyses and retrospective data. Therefore, adequate pretreatment assessments are vital to anticipate factors that may contribute to morbidity during therapy. In addition, supportive care during treatment is essential. For patients of all ages who present with early or localized disease, curative treatment should be offered whenever possible. With more precise surgical and radiologic techniques, the ability to provide curative treatment while minimizing long-term toxicity has greatly improved. Not only our techniques but also our understanding of the disease have improved. Human papillomavirus (HPV)-related HNSCC has changed the treatment paradigm of advanced-stage disease because of the inherently better prognosis compared with tobacco- and alcohol-related HNSCC. How this will affect early-stage disease remains to be seen, but de-escalated therapy may prove a suitable strategy in eligible elderly patients. With improved therapies and understanding of the disease, additional prospective trials must be carried out in the elderly population.

Definitive chemoradiation for locally-advanced oral cavity cancer: A 20-year experience.

OBJECTIVES: Definitive chemoradiation (CRT) for oral cavity squamous cell carcinoma (OC-SCC) is often criticized for poor efficacy or toxicity. We describe a favorable 20-year experience of primary CRT for locally-advanced OC-SCC. MATERIALS AND METHODS: Patients with locally-advanced, stage III/IV OC-SCC receiving primary concomitant CRT on protocols from 1994 to 2014 were analyzed. Chemotherapy included fluorouracil and hydroxyurea with other third agents. Radiotherapy (RT) was delivered once or twice daily to a maximum dose of 70-75 Gy. Intensity-modulated RT (IMRT) was exclusively used after 2004. Progression-free survival (PFS), overall survival (OS), locoregional control (LRC), and distant control (DC) were calculated by the Kaplan-Meier method and compared across treatment decades using the log-rank test. Rates of osteoradionecrosis (ORN) requiring surgery were compared across treatment decades using the Chi-square test. RESULTS: 140 patients with locally-advanced OC-SCC were treated with definitive CRT. Of these, 75.7% had T3/T4 disease, 68.6% had ≥N2 nodal disease, and 91.4% had stage IV disease. Most common primary sites were oral tongue (47.9%) and floor of mouth (24.3%). Median follow-up was 5.7 years. Five-year OS, PFS, LRC, and DC were 63.2%, 58.7%, 78.6%, and 87.2%, respectively. Rates of ORN and long-term feeding tube dependence were 20.7% and 10.0%, respectively. Differences in LRC (P = 0.90), DC (P = 0.24), PFS (P = 0.38), OS (P = 0.10), or ORN (P = 0.38) were not significant across treatment decades. CONCLUSION: Definitive CRT is a viable and feasible strategy for organ preservation for patients with locally-advanced OC-SCC.

Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer.

PURPOSE: The role of cetuximab in the treatment of locoregionally advanced head and neck squamous cell cancer (LA-HNSCC) remains poorly defined. In this phase 2 randomized study, we investigated the addition of cetuximab to both induction chemotherapy (IC) and hyperfractionated or accelerated chemoradiation. METHODS AND MATERIALS: Patients with LA-HNSCC were randomized to receive 2 cycles of weekly IC (cetuximab, paclitaxel, carboplatin) and either Cetux-FHX (concurrent cetuximab, 5-fluorouracil, hydroxyurea, and 1.5 Gy twice-daily radiation therapy every other week to 75 Gy) or Cetux-PX (cetuximab, cisplatin, and accelerated radiation therapy with delayed concomitant boost to 72 Gy in 42 fractions). The primary endpoint was progression-free survival (PFS), with superiority compared with historical control achieved if either arm had 2-year PFS ≥70%. RESULTS: 110 patients were randomly assigned to either Cetux-FHX (n=57) or Cetux-PX (n=53). The overall response rate to IC was 91%. Severe toxicity on IC was limited to rash (23% grade ≥3) and myelosuppression (38% grade ≥3 neutropenia). The 2-year rates of PFS for both Cetux-FHX (82.5%) and Cetux-PX (84.9%) were significantly higher than for historical control (P<.001). The 2-year overall survival (OS) was 91.2% for Cetux-FHX and 94.3% for Cetux-PX. With a median follow-up time of 72 months, there were no significant differences in PFS (P=.35) or OS (P=.15) between the treatment arms. The late outcomes for the entire cohort included 5-year PFS, OS, locoregional failure, and distant metastasis rates of 74.1%, 80.3%, 15.7%, and 7.4%, respectively. The 5-year PFS and OS were 84.4% and 91.3%, respectively, among human papillomavirus (HPV)-positive patients and 65.9% and 72.5%, respectively, among HPV-negative patients. CONCLUSIONS: The addition of cetuximab to IC and chemoradiation was tolerable and produced long-term control of LA-HNSCC, particularly among poor-prognosis HPV-negative patients. Further investigation of cetuximab may be warranted in the neoadjuvant setting and with non-platinum-based chemoradiation.

Phase III randomized trial of induction chemotherapy in patients with N2 or N3 locally advanced head and neck cancer.

PURPOSE: Induction chemotherapy (IC) before radiotherapy lowers distant failure (DF) rates in locally advanced squamous cell carcinoma of the head and neck (SCCHN). The goal of this phase III trial was to determine whether IC before chemoradiotherapy (CRT) further improves survival compared with CRT alone in patients with N2 or N3 disease. PATIENTS AND METHODS: Treatment-naive patients with nonmetastatic N2 or N3 SCCHN were randomly assigned to CRT alone (CRT arm; docetaxel, fluorouracil, and hydroxyurea plus radiotherapy 0.15 Gy twice per day every other week) versus two 21-day cycles of IC (docetaxel 75 mg/m(2) on day 1, cisplatin 75 mg/m(2) on day 1, and fluorouracil 750 mg/m(2) on days 1 to 5) followed by the same CRT regimen (IC + CRT arm). The primary end point was overall survival (OS). Secondary end points included DF-free survival, failure pattern, and recurrence-free survival (RFS). RESULTS: A total of 285 patients were randomly assigned. The most common grade 3 to 4 toxicities during IC were febrile neutropenia (11%) and mucositis (9%); during CRT (both arms combined), they were mucositis (49%), dermatitis (21%), and leukopenia (18%). Serious adverse events were more common in the IC arm (47% v 28%; P = .002). With a minimum follow-up of 30 months, there were no statistically significant differences in OS (hazard ratio, 0.91; 95% CI, 0.59 to 1.41), RFS, or DF-free survival. CONCLUSION: IC did not translate into improved OS compared with CRT alone. However, the study was underpowered because it did not meet the planned accrual target, and OS was higher than predicted in both arms. IC cannot be recommended routinely in patients with N2 or N3 locally advanced SCCHN.

Race and competing mortality in advanced head and neck cancer.

OBJECTIVES: Black patients with head and neck cancer (HNC) have poorer survival and disease control compared to non-black patients, but disparities in death from non-cancer causes (i.e., competing mortality) are less well-studied. MATERIALS AND METHODS: We conducted an analysis of 538 patients (169 black, 369 non-black) with stage III-IV HNC treated on one of six multi-institutional protocols between 1993 and 2004 involving multi-agent chemoradiotherapy with or without surgery. Competing mortality was defined as death due to intercurrent comorbid disease, treatment-related morbidity, or unknown cause in the absence of disease recurrence, progression, or second malignancy. Cox proportional hazards and competing risks regression were used to estimate the effect of black race on competing mortality. RESULTS: Black race was associated with increased rates of comorbidity, smoking, heavy alcohol use, advanced tumor stage, and poorer performance status (p<.001 for all). Compared to non-black patients, black HNC patients had a higher 5 year cumulative incidence of disease progression (31.4%; 95% CI, 24.4-38.5% vs 23.4%; 95% CI, 19.1-28.1%) and competing mortality (28.1%; 95% CI, 21.2-35.3% vs 14.5%; 95% CI, 11.0-18.5%). When adjusting for age, male sex, body mass index, distance traveled, smoking and alcohol use, performance status, comorbidity, and tumor stage, the black race was associated with death from comorbid disease (Cox hazard ratio 2.13; 95% CI, 1.06-4.28, p=0.033). CONCLUSIONS: Black patients with advanced HNC are at increased risk of both disease progression and death from competing non-cancer mortality, particularly death from comorbid disease. Improved strategies to manage comorbid disease may increase the benefit of treatment intensification in black patients.

Lymph node density--prognostic value in head and neck cancer.

BACKGROUND: The purpose of this study was to determine the prognostic value of lymph node density in head and neck cancer. METHODS: We utilized a prospective, multicenter database of 223 patients with head and neck cancer to identify patients who underwent lymph node dissection before chemoradiation to assess the prognostic significance of lymph node density. RESULTS: In 38 patients who met study criteria, lymph node density ≤0.20 predicted for improved overall survival (OS; 79% vs 50%; p = .04). Lymph node density was also associated with a trend toward improved 3-year locoregional control (96% vs 79%; p = .14) and distant metastasis-free survival (93% vs 78%; p = .13). In the patients with treatment failure distantly or locoregionally, that failure was earlier in patients with lymph node density >0.20 than in patients with lymph node density ≤0.20 (median, 12.7 months vs 5.2 months; p = .004). CONCLUSION: Our data suggest that lymph node density predicts for OS in patients with head and neck cancer and that the difference in OS may be because of differences in time to failure.

Survival and selected outcomes of older adults with locally advanced head/neck cancer treated with chemoradiation therapy.

OBJECTIVES: Chemoradiation therapy (CRT) remains a potentially curative treatment in patients with locally advanced head/neck cancer (LA-HNC). However, survival and other outcomes in older patients with head/neck cancer receiving chemoradiotherapy are not well established. This study was performed to elucidate selected outcomes in this patient population. MATERIALS AND METHODS: Retrospective study of LA-HNC patients ≥ 70 years of age who had received 5-fluorouracil-hydoxyurea-based CRT with a minimum of 3 years of follow up after therapy initiation was performed. Pre-treatment patient- and cancer-related characteristics were recorded. Survival data in addition to gastrostomy tube utilization, swallowing function, and hematologic toxicity were captured. RESULTS: Eighty-nine patients treated between 1997 and 2009 were eligible for analysis (median age, 76 years; range, 70-94; male, 61%; ECOG PS, 0-1 43%; stage IVA/B, 71%). 86 were evaluable for survival analysis. 5-year overall and event-free survival were both at 32% with a median follow-up time of 39.2 months. The majority (86.5%) were able to complete all planned treatment cycles. A significant proportion of patients, however, required gastrostomy tube during CRT (62%) and developed aspiration during swallowing evaluation post-treatment (44%). Several patients required hospice (9%) or skilled nursing facility (13%) referrals during treatment. CONCLUSION: Select older adults with LA-HNC can still experience long-term benefits despite 5-year survival rates lower than those historically reported in younger patients undergoing identical CRT regimens although potentially at higher risk for acute toxicities. Assessment and selection of those who can tolerate more intense combined-modality strategies and their long-term outcomes merit further larger, prospective studies.

Performance and quality of life outcomes for T4 laryngeal cancer patients treated with induction chemotherapy followed by chemoradiotherapy.

Organ-sparing approaches with chemoradiotherapy are often used in the treatment of patients with laryngeal cancer, and the oncologic outcomes of these patients are similar to patients who undergo laryngectomy. However, chemoradiotherapy for laryngeal cancer patients with large or locally-invasive (T4) tumors has been more slowly incorporated due to concern for poor post-treatment function of the preserved larynx. Here, we characterize acute and long-term performance and quality-of-life (QOL) outcomes of T4 laryngeal cancer patients treated with induction chemotherapy followed by combined chemoradiotherapy. Using several validated metrics, we find patients experience a decline in most measures of performance and QOL during and immediately following treatment. However, the majority of patients improve to baseline over varying lengths of time following completion of treatment, and many go on to exceed pre-treatment levels of function. Gender, race, alcohol, and tobacco usage were found to be associated with differences in performance and QOL scores across time points. This study suggests that patients with advanced laryngeal tumors who historically had been considered poor candidates for organ-sparing treatment are able to return to, and in many cases exceed pre-treatment performance and QOL following induction chemotherapy and combined chemoradiotherapy.

Stereotactic body radiotherapy for multisite extracranial oligometastases: final report of a dose escalation trial in patients with 1 to 5 sites of metastatic disease.

BACKGROUND: A subset of patients with metastatic cancer in limited organs may benefit from metastasis-directed therapy. The authors investigated whether patients with limited metastases could be safely treated with metastasis-directed radiotherapy. METHODS: Patients with 1 to 5 metastatic cancer sites with a life expectancy of >3 months received escalating stereotactic body radiotherapy (SBRT) doses to all known cancer sites. Patients were followed radiographically with CT scans of the chest, abdomen, and pelvis and metabolically with fluorodeoxyglucose-positron emission tomography, 1 month after treatment, and then every 3 months. Acute toxicities were scored using the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0, and late toxicities were scored using the Radiation Therapy Oncology Group late toxicity scoring system. RESULTS: Sixty-one patients with 113 metastases were enrolled from November 2004 to November 2009 on a prospective radiation dose escalation study. Median follow-up was 20.9 months. Patients tolerated treatment well; the maximal tolerated dose was not reached in any cohort. Eleven patients (18.3%) have not progressed. One and 2-year progression-free survival are 33.3% (95% confidence interval [CI], 22.8-46.1) and 22.0% (95% CI, 12.8-34.4); 1-year and 2-year overall survival are 81.5% (95% CI, 71.1-91.1) and 56.7% (95% CI, 43.9-68.9). Seventy-two percent of patients whose tumors progressed did so in limited (1-3) metastatic sites. CONCLUSIONS: Patients with 1 to 5 metastases can be safely treated to multiple body sites and may benefit from SBRT. Further investigation should focus on patient selection.

Chemoradiation for patients with large-volume laryngeal cancers.

BACKGROUND: Patients with T4 laryngeal cancers, including those with large-volume (cartilage or tongue-base invasion) lesions, are often excluded from organ-preservation trials due to expectations of inferior outcome in terms of survival and function. We hypothesize that such patients indeed have acceptable survival and function when treated with organ-preservation strategies. METHODS: Retrospective analysis of prospectively collected data of a cohort of patients with T4 laryngeal cancer was carried out. Follow-up ranged from 0.18 to 15.6 years. All T4 laryngeal cancer patients who were enrolled in the University of Chicago concomitant chemoradiotherapy protocols from 1994 to the present were reviewed. This study was composed of 80 newly diagnosed T4 laryngeal cancer patients. Efficacy of treatment was determined through evaluations of survival and function. Survival was evaluated via Kaplan-Meier methods. Swallowing function was evaluated by an oropharyngeal motility (OPM) study and swallowing scores were assigned. Higher scores reflected increasing swallowing dysfunction. RESULTS: Fifty-five of 80 patients (~69%) had documented large-volume tumor. Two- and 5-year overall survivals were 60.0% and 48.7%, respectively. Disease-specific 2- and 5-year survivals for the group were 80.1% and 71.3%, and 79.4 and 74.3%, respectively, for the 55 patients with large volume status. Progression-free survival rates were 52.6% and 47.6%. Forty-four of 65 patients (~68%) with OPM data had a Swallowing Performance Status Scale (SPSS) score of ≤5, indicating various degrees of swallowing abnormalities not requiring a gastrostomy tube. This is a functional-preservation rate of 67.7%. CONCLUSIONS: Chemoradiation for patients with T4 laryngeal cancer appears to be an effective and reasonable option, particularly in light of the satisfactory survival and function-preservation rates.

Hypofractionated image-guided radiation therapy for patients with limited volume metastatic non-small cell lung cancer.

INTRODUCTION: Outcomes data treating patients with oligometastatic (≤ 5 metastases) non-small cell lung carcinoma (NSCLC) with hypofractionated image-guided radiotherapy (HIGRT) are limited. METHODS: Consecutive oligometastatic NSCLC patients were reviewed from a prospective database. Patients were included if all active diseases were treated with HIGRT. Lesions that had received prior radiation or had radiographic/metabolic resolution after chemotherapy were not treated with HIGRT. Local control of all treated lesions, distant control, progression-free survival (PFS), overall survival (OS), and control of individual lesions (LeC) were calculated. RESULTS: Twenty-five patients with median of 2 treated oligometastatic lesions were included. Median follow-up was 14 months. Median age was 66 years. Nineteen patients received systemic therapy before HIGRT and 11 had progressive disease after their most recent systemic therapy before HIGRT. Median OS and PFS were 22.7 and 7.6 months. The 18 months local control, distant control, OS, and PFS were 66.1%, 31.7%, 52.9%, and 28.0%. Greater than two sites treated with HIGRT, nonadenocarcinoma histology, prior systemic therapy, and progression after systemic therapy were associated with worse PFS. Sixty-two individual lesions of median size 2.7 cm were treated. For extracranial lesions, median total and fraction dose were 50 and 5 Gy. Median standard equivalent dose in 2 Gy fractions for extracranial lesions was 64.6 Gy yielding 18 months LeC of 70.7%. Standard equivalent dose ≥64.6 Gy increased LeC (p = 0.04). Two patients experienced grade 3 toxicity. CONCLUSIONS: HIGRT for oligometastatic NSCLC provides durable LeC and may provide long-term PFS in some patients. Future HIGRT studies should optimize patient selection and integration with systemic therapy.

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies.

BACKGROUND: To report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy. METHODS: From 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m² on d1), infusional 5-fluorouracil (600 mg/m²/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. RESULTS: Median follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1). CONCLUSIONS: Surgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.