Search

Press Coverage from Racial Survival Disparity in Head and Neck Cancer Results from Low Prevalence of Human Papillomavirus Infection in Black Oropharyngeal Cancer Patients

Perspective on This Article from Racial Survival Disparity in Head and Neck Cancer Results from Low Prevalence of Human Papillomavirus Infection in Black Oropharyngeal Cancer Patients

ImportanceFor many types of epithelial malignant neoplasms that are treated with definitive radiotherapy (RT), treatment prolongation and interruptions have an adverse effect on outcomes.ObjectiveTo analyze the association between RT duration and outcomes in patients with esophageal cancer who were treated with definitive chemoradiotherapy (CRT).Design, Setting, and ParticipantsThis study was an unplanned, post hoc secondary analysis of 3 prospective, multi-institutional phase 3 randomized clinical trials (Radiation Therapy Oncology Group [RTOG] 8501, RTOG 9405, and RTOG 0436) of the National Cancer Institute–sponsored NRG Oncology (formerly the National Surgical Adjuvant Breast and Bowel Project, RTOG, and Gynecologic Oncology Group). Enrolled patients with nonmetastatic esophageal cancer underwent definitive CRT in the trials between 1986 and 2013, with follow-up occurring through 2014. Data analyses were conducted between March 2022 to February 2023.ExposuresTreatment groups in the trials used standard-dose RT (50 Gy) and concurrent chemotherapy.Main Outcomes and MeasuresThe outcomes were local-regional failure (LRF), distant failure, disease-free survival (DFS), and overall survival (OS). Multivariable models were used to examine the associations between these outcomes and both RT duration and interruptions. Radiotherapy duration was analyzed as a dichotomized variable using an X-Tile software to choose a cut point and its median value as a cut point, as well as a continuous variable.ResultsThe analysis included 509 patients (median [IQR] age, 64 [57-70] years; 418 males [82%]; and 376 White individuals [74%]). The median (IQR) follow-up was 4.01 (2.93-4.92) years for surviving patients. The median cut point of RT duration was 39 days or less in 271 patients (53%) vs more than 39 days in 238 patients (47%), and the X-Tile software cut point was 45 days or less in 446 patients (88%) vs more than 45 days in 63 patients (12%). Radiotherapy interruptions occurred in 207 patients (41%). Female (vs male) sex and other (vs White) race and ethnicity were associated with longer RT duration and RT interruptions. In the multivariable models, RT duration longer than 45 days was associated with inferior DFS (hazard ratio [HR], 1.34; 95% CI, 1.01-1.77; P = .04). The HR for OS was 1.33, but the results were not statistically significant (95% CI, 0.99-1.77; P = .05). Radiotherapy duration longer than 39 days (vs ≤39 days) was associated with a higher risk of LRF (HR, 1.32; 95% CI, 1.06-1.65; P = .01). As a continuous variable, RT duration (per 1 week increase) was associated with DFS failure (HR, 1.14; 95% CI, 1.01-1.28; P = .03). The HR for LRF 1.13, but the result was not statistically significant (95% CI, 0.99-1.28; P = .07).Conclusions and RelevanceResults of this study indicated that in patients with esophageal cancer receiving definitive CRT, prolonged RT duration was associated with inferior outcomes; female patients and those with other (vs White) race and ethnicity were more likely to have longer RT duration and experience RT interruptions. Radiotherapy interruptions should be minimized to optimize outcomes.

Purpose/Objective(s) Standard of care for surgical candidates with locally advanced esophageal/gastroesophageal junction (E/GEJ) cancers is trimodality therapy. Similar to other groups, we have previously demonstrated the strong prognostic significance of pathological complete response (pCR) at the time of esophagectomy. Little is known about the prognostic significance of nodal clearance alone, however. We sought to determine the prognostic significance of nodal clearance in the subgroup of node positive E/GEJ (N+ E/GEJ), hypothesizing that nodal clearance drives the improved outcomes seen in patients with pCR as the primary tumor is more completely removed at esophagectomy. Materials/Methods Patients undergoing TMT for a primary N+ E/GEJ cancer from 1993-2020 within a single institution were retrospectively analyzed. All patients had either clinically involved nodal disease prior to nCRT and/or pathologically confirmed residual nodal disease at time of esophagectomy. Cancer and demographic features were collected. Direct comparisons were made between pCR versus no pCR and nodal clearance (ypN0) versus persistent nodal disease (ypN+) using the Kaplan-Meier method to estimate progression free survival (PFS) and overall survival (OS). Results One hundred eighty-one patients with median follow up of 140 months were included for analysis. Median age at diagnosis was 60.1 years (30.1-80.9), 142 (78.5%) were adenocarcinomas, 102 (56.4%) were AJCC stage IIIA. Fifty-one (28.2%) had pCR, 103 (56.9%) had ypN0 (including 52 [28.7%] with nodal clearance and residual tumor) and 78 (43.1%) had ypN+. Median OS and PFS for the entire cohort were 26.4 (95% CI, 20.5-32.3) and 18.0 months (95% CI, 12.7-23.4), respectively; 2-year local control rate was 87.4% (95% CI, 84.6-90.2). When comparing ypN0 to ypN+, there were statistically significant improvements in OS and PFS. In contrast, there were no significant differences in OS and PFS when comparing patients with pCR to no pCR (Table 1). Conclusion While pCR is a known prognostic factor in E/GEJ regardless of nodal status, in the high-risk subset of N+ E/GEJ patients, nodal clearance was associated with significantly improved OS and PFS regardless of primary tumor response. This is a novel observation and warrants similar hypothesis testing in other data sets and may have implications for therapy in node positive patients.

Objectives To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC). Material and methods Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively. Results The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome. Conclusions We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.

Purpose To determine, in a retrospective analysis of a large cohort of stage III non-small cell lung cancer patients treated with curative intent at our institution, whether having a pathologic complete response (pCR) influenced overall survival (OS) or freedom from recurrence (FFR) in patients who underwent definitive (≥60 Gy) neoadjuvant doses of chemoradiation (CRT). Methods and Materials At our institution, 355 patients with locally advanced non-small cell lung cancer were treated with curative intent with definitive CRT (January 2000-December 2013), of whom 111 underwent mediastinal reassessment for possible surgical resection. Ultimately 88 patients received trimodality therapy. Chi-squared analysis was used to compare categorical variables. The Kaplan-Meier analysis was performed to estimate OS and FFR, with Cox regression used to determine the absolute hazards. Results Using high-dose neoadjuvant CRT, we observed a mediastinal nodal clearance (MNC) rate of 74% (82 of 111 patients) and pCR rate of 48% (37 of 77 patients). With a median follow-up of 34.2 months (range, 3-177 months), MNC resulted in improved OS and FFR on both univariate (OS: hazard ratio [HR] 0.455, 95% confidence interval [CI] 0.272-0.763, P = .004; FFR: HR 0.426, 95% CI 0.250-0.726, P = .002) and multivariate analysis (OS: HR 0.460, 95% CI 0.239-0.699, P = .001; FFR: HR 0.455, 95% CI 0.266-0.778, P = .004). However, pCR did not independently impact OS (P = .918) or FFR (P = .474). Conclusions Mediastinal nodal clearance after CRT continues to be predictive of improved survival for patients undergoing trimodality therapy. However, a pCR at both the primary and mediastinum did not further improve survival outcomes. Future therapies should focus on improving MNC to encourage more frequent use of surgery and might justify use of preoperative CRT over chemotherapy alone.

SUMMARY: The objective of NRG Oncology RTOG 0123 was to test the ability of the angiotensin converting enzyme inhibitor (ACEI) captopril to reduce pulmonary damage after radiation for lung cancer. Despite significant effort, the trial did not analyze a sufficient number of patients to test the hypothesis due to early study closure. However, it did show the safety of the ACEI mitigation approach and the use of newer ACEIs, started during radiotherapy, may solve the accrual problems. OBJECTIVES: The primary objective of NRG Oncology RTOG 0123 was to test the ability of the angiotensin converting enzyme inhibitor (ACEI) captopril to alter the incidence of pulmonary damage after radiation therapy for lung cancer; secondary objectives included analyzing pulmonary cytokine expression, quality of life, and the long-term effects of captopril. METHODS: Eligible patients included Stage II-IIIB non-small cell lung cancer, Stage I central NSCLC, or limited-stage small-cell. Patients who met eligibility for randomization at the end of radiotherapy received either captopril or standard care for one year. The captopril was to be escalated to 50 mg TID. Primary endpoint was incidence of Grade 2+ radiation-induced pulmonary toxicity in the first year. RESULTS: 81 patients were accrued between 6/2003 and 8/2007. Given the low accrual rate, the study was closed early. No significant safety issues were encountered. Eight patients were ineligible for registration or withdrew consent prior to randomization and 40 patients were not randomized post-radiation. Major reasons for non-randomization included patients' refusal and physician preference. Of the 33 randomized patients, 20 were analyzable (13 observation, 7 captopril). The incidence of Grade 2+ pulmonary toxicity attributable to radiation therapy was 23% (3/13) in the observation arm and 14% (1/7) in the captopril arm. CONCLUSION: Despite significant resources and multiple amendments, NRG Oncology RTOG 0123 was unable to test the hypothesis that captopril mitigates radiation-induced pulmonary toxicity. It did show the safety of such an approach and the use of newer ACEIs started during radiotherapy may solve the accrual problems.

Relative radiation dose exposure to vital organs in the thorax could influence clinical outcomes in esophageal cancer (EC). We assessed whether the type of radiation therapy (RT) modality used was associated with postoperative outcomes after neoadjuvant chemoradiation (nCRT).Contemporary data from 580 EC patients treated with nCRT at 3 academic institutions from 2007 to 2013 were reviewed. 3D conformal RT (3D), intensity modulated RT (IMRT) and proton beam therapy (PBT) were used for 214 (37%), 255 (44%), and 111 (19%) patients, respectively. Postoperative outcomes included pulmonary, GI, cardiac, wound healing complications, length of in-hospital stay (LOS), and 90-day postoperative mortality. Cox model fits, and log-rank tests both with and without Inverse Probability of treatment Weighting (IPW) were used to correct for bias due to non-randomization.RT modality was significantly associated with the incidence of pulmonary, cardiac and wound complications, which also bore out on multivariate analysis. Mean LOS was also significantly associated with treatment modality (13.2days for 3D (95%CI 11.7-14.7), 11.6days for IMRT (95%CI 10.9-12.7), and 9.3days for PBT (95%CI 8.2-10.3) (p0.0001)). The 90day postoperative mortality rates were 4.2%, 4.3%, and 0.9%, respectively, for 3D, IMRT and PBT (p=0.264).Advanced RT technologies (IMRT and PBT) were associated with significantly reduced rate of postoperative complications and LOS compared to 3D, with PBT displaying the greatest benefit in a number of clinical endpoints. Ongoing prospective randomized trial will be needed to validate these results.

Population studies suggest an impact of insurance status on oncologic outcomes. We sought to explore this in a large single-institution cohort of patients with non-small-cell lung cancer (NSCLC).We retrospectively analyzed 342 consecutive patients (January 2000 to December 2013) curatively treated for stage III NSCLC. Patients were categorized by insurance status as uninsured (U), Medicare/Medicaid + Veterans Affairs (M/M + VA), or Private (P). The χCompared with M/M + VA patients, P insurance patients were more likely to be younger (P .001), married (P .001), Caucasian (P = .001), reside in higher median income zip codes (P .001), have higher performance status (P .001), and undergo consolidation chemotherapy (P .001) and trimodality therapy (P .001). Diagnosis to treatment was delayed30 days in U (67.3%), M/M + VA (68.1%), and P (52.6%) patients (P = .017). Compared with the M/M + VA and U cohorts, P insurance patients had improved OS (median/5-year: 30.7 months/34.2%, 19 months/17%, and 16.9 months/3.8%; P .001) and FFR (median/5-year: 18.4 months/27.3%, 15.2 months/23.2%, and 11.4 months/4.8%; P = .012), respectively. On multivariate analysis, insurance status was an independent predictor for OS (P = .017) but not FFR.Compared with U or M/M + VA patients, P insurance patients with stage III NSCLC were more likely to be optimally diagnosed and treated, resulting in a doubling of median OS for P versus U patients. Improved access to affordable health insurance is critical to combat inequities in access to care and has potential for improvements in cancer outcomes.

BACKGROUND Prospective quality metrics for neck dissection have not been established for patients with head and neck squamous cell carcinoma. The purpose of this study was to investigate the association between lymph node counts from neck dissection, local-regional recurrence, and overall survival. METHODS The number of lymph nodes counted from neck dissection in patients treated in 2 NRG Oncology trials (Radiation Therapy Oncology Group [RTOG] 9501 and RTOG 0234) was evaluated for its prognostic impact on overall survival with a multivariate Cox model adjusted for demographic, tumor, and lymph node data and stratified by the postoperative treatment group. RESULTS Five hundred seventy-two patients were analyzed at a median follow-up of 8 years. Ninety-eight percent of the patients were pathologically N+. The median numbers of lymph nodes recorded on the left and right sides were 24 and 25, respectively. The identification of fewer than 18 nodes was associated with worse overall survival in comparison with 18 or more nodes (hazard ratio [HR], 1.38; 95% confidence interval [CI], 1.09-1.74; P = .007). The difference appeared to be driven by local-regional failure (HR, 1.46; 95% CI, 1.02-2.08; P = .04) but not by distant metastases (HR, 1.08; 95% CI, 0.77-1.53; P = .65). When the analysis was limited to NRG Oncology RTOG 0234 patients, adding the p16 status to the model did not affect the HR for dissected nodes, and the effect of nodes did not differ with the p16 status. CONCLUSIONS The removal and identification of 18 or more lymph nodes was associated with improved overall survival and lower rates of local-regional failure, and this should be further evaluated as a measure of quality in neck dissections for mucosal squamous cell carcinoma. Cancer 2016;122:3464–71. © 2016 American Cancer Society.

Introduction The objective of this retrospective study was to determine the potential benefits of chemotherapy in esophageal cancer patients treated with chemoradiation followed by surgery. Materials and methods At our institution, 145 patients completed trimodality therapy from 1993 to 2009. Neoadjuvant treatment predominantly consisted of 5-fluorouracil and cisplatin with a concurrent median radiation dose of 50.4 Gy. Sixty-two patients received chemotherapy postoperatively. The majority (49/62) received 3 cycles of docetaxel. Results Within the entire cohort, a 5-year overall survival (OS) benefit was found in those who received postoperative chemotherapy, OS 37.1% versus 18.0% (P=0.024). The response after neoadjuvant chemoradiation was as follows: 33.8% had a pathologic complete response and 62.8% with residual disease. A 5-year OS and cause-specific survival (CSS) advantage were associated with postoperative chemotherapy among those with macroscopic residual disease after neoadjuvant therapy: OS 38.7% versus 13.9% (P=0.016), CSS 42.8% versus 18.8% (P=0.048). This benefit was not seen in those with a pathologic complete response or those with microscopic residual. A stepwise multivariate Cox regression model evaluating the partial response group revealed that postoperative chemotherapy and M stage were independent predictors of overall and CSS. Conclusions This analysis revealed that patients with gross residual disease after trimodality therapy for esophageal cancer who received postoperative chemotherapy had an improved overall and CSS. These data suggest that patients with residual disease after trimodality therapy and a reasonable performance status may benefit from postoperative chemotherapy. Prospective trials are needed to confirm these results to define the role of postoperative treatment after trimodality therapy.

Background We questioned whether the National Comprehensive Cancer Network recommendations for brain magnetic resonance imaging (MRI) for patients with stage ≥ IB non–small-cell lung cancer (NSCLC) was high-yield compared with American College of Clinical Pharmacy and National Institute for Health and Care Excellence guidelines recommending stage III and above NSCLC. We present the prevalence and factors predictive of asymptomatic brain metastases at diagnosis in patients with NSCLC without extracranial metastases. Materials and Methods A retrospective analysis of 193 consecutive, treatment-naive patients with NSCLC diagnosed between January 2010 and August 2015 was performed. Exclusion criteria included no brain MRI staging, symptomatic brain metastases, or stage IV based on extracranial disease. Univariate and multivariate logistic regression was performed. Results The patient characteristics include median age of 65 years (range, 36-90 years), 51% adenocarcinoma/36% squamous carcinoma, and pre-MRI stage grouping of 31% I, 22% II, 34% IIIA, and 13% IIIB. The overall prevalence of brain metastases was 5.7% (n = 11). One (2.4%) stage IA and 1 (5.6%) stage IB patient had asymptomatic brain metastases at diagnosis, both were adenocarcinomas. On univariate analysis, increasing lymph nodal stage (P = .02), lymph nodal size > 2 cm (P = .009), multi-lymph nodal N1/N2 station involvement (P = .027), and overall stage (P = .005) were associated with asymptomatic brain metastases. On multivariate analysis, increasing lymph nodal size remained significant (odds ratio, 1.545; P = .009). Conclusion Our series shows a 5.7% rate of asymptomatic brain metastasis for patients with stage I to III NSCLC. Increasing lymph nodal size was the only predictor of asymptomatic brain metastases, suggesting over-utilization of MRI in early-stage disease, especially in lymph node-negative patients with NSCLC. Future efforts will explore the utility of baseline MRI in lymph node-positive stage II and all stage IIIA patients.

Background Racial outcome disparities have been observed in head and neck squamous cell carcinoma (HNSCC) with diminished survival for black patients compared with white patients. Methods We retrospectively analyzed 1318 patients with primary HNSCC treated at the University of Maryland Greenebaum Cancer Center (UMGCC) from 2000 to 2010. Results Of all the patients, 65.9% were white, 30.7% were black, and 3.3% were of other races. Black patients were less likely to present with oral cavity cancer, and more likely to present with laryngeal or hypopharyngeal cancers. White patients were more likely to have early stage disease, especially in the oral cavity. Black race was independently associated with worse overall survival (OS) in the entire cohort. Black patients had a significantly worse OS among oral cavity and oropharyngeal cancers, with the largest disparity in oropharyngeal cancer. However, in multivariate analysis, race was only still significant in oropharyngeal cancer. Conclusion We observed differences by race in distribution of disease site, stage, and OS. Survival disparity in the entire cohort was driven mostly by differences among oropharyngeal cancer.

Purpose This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). Methods and Materials The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. Results A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% ( P =.42), local-regional progression-free survival was 31.5% versus 37.6% ( P =.20), and overall survival was 36.9% versus 38.2% ( P =.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. Conclusions This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

This study investigated the relationship between tumor volume and outcomes in patients receiving trimodality therapy for locally advanced esophageal cancer.Between 2001 and 2012, 67 patients treated for esophageal cancer with chemoradiotherapy followed by esophagectomy who had available gross tumor volume (GTV) information were analyzed (35 node-negative, 32 node-positive patients with primary and nodal GTV contoured as separate regions of interest). All gross tumor volumes (GTVs) were contoured at the time of radiotherapy treatment planning. GTV optimal cutoff values were determined with receiver operating characteristic analysis and deemed significant when χ (2) analysis demonstrated differences in examined prognostic variables. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model.GTVprimary (P = 0.034) and N stage were significant multivariate predictors for improved local control; GTVprimary was the only multivariate predictor of PFS (P = 0.0299) and OS (P = 0.001228) at 5 years. Univariate predictors of 5-year PFS and OS included GTVprimary, node number, and metastatic lymph node ratio. GTVprimary85 cc was the best predictor for local failure (33.3 %; 8.7 % if ≤85 cc). GTVprimary46 cc correlated with an increased risk of 5-year distant failure (37.1 %; 6.7 % if ≤46 cc).GTVprimary was a significant multivariate predictor for improved local control, PFS, and OS. GTVprimary is a more powerful predictor of patient outcomes than traditional TNM staging and should be part of the decision-making process when determining optimal local and systemic options for patients with locally advanced esophageal cancer.

We conducted a phase I dose escalation study to evaluate the safety and immunologic response to peptide immunomodulatory vaccines GL-0810 (HPV16) and GL-0817 (MAGE-A3) in HPV16 and MAGE-A3-positive RM–SCCHN patients, respectively. Three dose levels (500, 1,000, and 1,500 µg) of GL-0810 or GL-0817 with adjuvants Montanide (1.2 ml) and GM-CSF (100 µg/m2) were administered subcutaneously q2 weeks for a total of four vaccinations in HPV16 and MAGE-A3-positive RM–SCCHN patients, respectively. Nine and seven patients were enrolled in the HPV16 and MAGE-A3 cohorts, respectively. No dose-limiting toxicities were observed, and toxicity was predominantly local and grade 1 (erythema, pain, and itching at the injection site). In those patients who received all four vaccinations, 80 % (4/5) of the HPV16 cohort and 67 % (4/6) of the MAGE-A3 cohort developed antigen-specific T cell and antibody responses to the vaccine. Significant concordance between T cell and antibody responses was observed for both groups. No clear dose–response correlation was seen. All patients progressed by RECIST at first repeat imaging, except for one patient in the MAGE-A3 500 µg cohort who had stable disease for 10.5 months. The median PFS and OS for the MAGE-A3 cohorts were 79 and 183 days, respectively, and for the HPV16 cohort 80 and 196 days, respectively. GL-0810 and GL-0817 were well tolerated in patients with RM–SCCHN with T cell and antibody responses observed in the majority of patients who received all four vaccinations.

The black population remains underrepresented in clinical trials despite reports suggesting greater incidence and deaths from locally advanced non-small cell lung cancer (NSCLC). We determined outcomes for black and non-black patients in a well-annotated cohort treated with either definitive chemoradiation (CRT; bimodality) or CRT followed by surgery (trimodality therapy).A retrospective analysis of 355 stage III NSCLC patients treated with curative intent at the University of Maryland, Medical Center, between January 2000-December 2013 was performed. The Kaplan-Meier approach and the Cox proportional hazards models were used to analyze overall survival (OS) and freedom-from-recurrence (FFR) in black and non-black patients. The chi-square test was used to compare categorical variables.Black patients comprised 42% of the cohort and were more likely to be younger (p0.0001), male (p=0.030), single (p0.0001), reside in lower household income zipcodes (p0.0001), have an Eastern Cooperative Oncology Group (ECOG) performance status0 (p0.001), and less likely to undergo surgery (p0.0001). With a median follow-up of 15 months for all patients and 89 months for surviving patients (range:1-186 months), median OS times for black and non-black patients were 22 and 24 months, respectively (p=0.698). FFR rates were also comparable between the two groups (p=0.468). Surgery improved OS in both cohorts. Race was not a significant predictor for OS or FFR even when adjusted for other factors.We found similar oncologic outcomes in black and non-black NSCLC patients when treated with curative intent in a comprehensive cancer center setting, despite epidemiologic differences in presentation and receipt of care. Future efforts to improve outcomes in black patients could focus on addressing modifiable social disparities.

Objective Concern exists regarding surgery after thoracic radiation. We aimed to assess early results of anatomic resection following induction therapy with platinum-based chemotherapy and full-dose thoracic radiation for resectable N2+ stage IIIA non–small cell lung cancer. Methods Two prospective trials were recently conducted by NRG Oncology in patients with resectable N2+ stage IIIA non–small cell lung cancer with the primary end point of mediastinal node sterilization following concurrent full-dose chemoradiotherapy (Radiation Therapy Oncology Group trials 0229 and 0839). All surgeons demonstrated postinduction resection expertise. Induction consisted of weekly carboplatin (area under the curve, 2.0) and paclitaxel (50 mg/m2) and concurrent thoracic radiation 60 Gy (0839)/61.2 Gy (0229) in 30 fractions. Patients in study 0839 were randomized 2:1 to weekly panitumumab + chemoradiotherapy or chemoradiotherapy alone during induction. Primary results were similar in all treatment arms and reported previously. Short-term surgical outcomes are reported here. Results One hundred twenty-six patients enrolled; 93 (74%) had anatomic resection, 77 underwent lobectomy, and 16 underwent extended resection. Microscopically margin-negative resections occurred in 85 (91%). Fourteen (15%) resections were attempted minimally invasively, including 2 converted without event. Grade 3 or 4 surgical adverse events were reported in 26 (28%), 30-day mortality in 4 (4%) and 90-day mortality in 5 (5%). Patients undergoing extended resection experienced similar rates of grade 3 or 4 adverse events (odds ratio, 0.95; 95% confidence interval, 0.42-3.8) but higher 30-day (1.3% vs 18.8%) (odds ratio, 17.54; 95% confidence interval, 1.75-181.8) and 90-day mortality (2.6% vs 18.8%) (odds ratio, 8.65; 95% confidence interval, 1.3-56.9). Conclusions Lobectomy was performed safely following full-dose concurrent chemoradiotherapy in these multi-institutional prospective trials; however, increased mortality was noted with extended resections.

Purpose: Guidelines for locally advanced non-small cell lung cancer (LA-NSCLC) recommend definitive chemoradiation therapy (CRT) for cN2-N3 disease, reserving surgery for patients with minimal nodal involvement at presentation. The current literature suggests that surgery after CRT for stage III NSCLC can improve freedom-from-recurrence (FFR) but has not consistently demonstrated an improvement in overall survival, perhaps partly due to the low (45-50.4 Gy) preoperative doses delivered that result in low rates of mediastinal nodal clearance. We therefore analyzed factors associated with trimodality therapy receipt and determined outcomes in patients with LA-NSCLC who were treated with definitive doses (≥60 Gy) of neoadjuvant CRT prior to surgery. Methods and materials: We retrospectively analyzed 355 consecutive patients with LA-NSCLC who were treated with curative intent between January 2000 and December 2013. The Kaplan-Meier method was used to estimate the overall survival and FFR of patients who were initially planned to receive trimodality treatment but never underwent surgery (unplanned bimodality) compared with those who were never considered to be surgical candidates (planned bimodality) and those who underwent surgical resection after CRT (trimodality). Cox proportional hazards regression with forward selection was used for multivariate analyses, and the Fisher exact test was used to test contingency tables. Results: Patients who received trimodality therapy had a longer median survival than those with unplanned or planned bimodality therapy at 59.9, 20.1, and 17.3 months, respectively (P < .001). The survival benefit with surgery persisted in patients with stage IIIB (P < .001) and N3 (P = .010) nodal disease when mediastinal nodal clearance was achieved. FFR was also improved with surgical resection (P = .001). Race (P < .001), stage (P < .001), performance status (P < .001), age (P < .001), and diagnosis of chronic obstructive pulmonary disease (P = .009) were significant indicators that influenced both the decision to initially choose trimodality therapy at consultation and to actually perform surgical resection. Conclusions: Trimodality treatment significantly improves survival and FFR in patients with LA-NSCLC when definitive doses of radiation with neoadjuvant chemotherapy are employed. We identified important demographic features that predict the use of surgical intervention in patients with stage III NSCLC.

The purpose of this work was to find potential trends in RECIST measurements and volume regressions obtained from weekly cone-beam computed tomography images and to evaluate their relationship to clinical outcomes in locally advanced head and neck cancer. We examined thirty head and neck cancer patients who underwent a pre-treatment planning CT and weekly cone-beam computed tomography (CBCT) during the 5-7 week treatment period. The gross tumor volume (GTV) and lymph nodes were manually contoured on the treatment planning CT. The regions of interest enclosed by delineated contours were converted to binary masks and warped to weekly CBCT images using the 3D deformation field obtained by deformable image registration. The RECIST diameters and volumes were measured from these warped masks. Different predictor variables based on these measurements were calculated and correlated with clinical outcomes, based on a clinical exam and a PET imaging study. We found that there was substantial regression of the gross tumor volume over the treatment course (average gross tumor volume regression of 25%). Among the gross tumor volume predicators, it was found that the early regression of gross tumor volume showed a marginal statistical significance (p = 0.045) with complete response and non-complete response treatment outcomes. RECIST diameter measurements during treatment varied very little and did not correlate with clinical outcomes. We concluded that regression of the gross tumor volume obtained from weekly CBCT images is a promising predictor of clinical outcomes for head and neck patients. A larger sample is needed to confirm its statistical significance.

Summary The study aimed to examine whether omission of 5-fluorouracil (5-FU)-containing chemotherapy alters pathological complete response rates in patients receiving trimodality therapy for locally advanced esophageal cancer. A total of 159 patients were identified. One hundred twenty-nine patients received platinum/5-FU concurrently with radiotherapy, and 30 received taxane/platinum-containing chemoradiotherapy prior to esophagectomy. Patients were staged using the 2002 American Joint Committee on Cancer staging system. Patients were matched between chemotherapeutic groups, with no significant demographic or clinical differences other than T stage (14% T2 in the 5-FU group; no T2 in the platinum/taxane group) and radiotherapy technique (8.5% received intensity-modulated radiotherapy in the 5-FU group; 60% in the platinum/taxane group). Pathological complete response rates for 5-FU and platinum/taxane-based groups were not significantly different (45% and 30%, respectively; P = 0.1548). Five-year overall survival and progression-free survival were not statistically different between the two groups. Significant predictors of pathological complete response included N stage (56% N0 and 33% N1; P = 0.0083), histology (37% adenocarcinoma and 59% squamous cell; P = 0.0123), tumor location (39% distal and 59% proximal/mid; P = 0.048), gastroesophageal junction involvement (33% involved and 55% uninvolved; P = 0.005), and radiotherapy end-to-surgery interval (50% < 55 days and 34% ≥ 55 days; P = 0.04). Grades 3–4 hematological toxicity was higher in the 5-FU group (36%) than in the paclitaxel-containing therapy group (17%; P = 0.0484). Use of paclitaxel-containing chemoradiotherapy did not result in inferior pathological complete response, overall survival, or progression-free survival rates, and resulted in less hematological toxicity than 5-FU treatment.

Purpose To construct predictive models using comprehensive tumor features for the evaluation of tumor response to neoadjuvant chemoradiation therapy (CRT) in patients with esophageal cancer. Methods and Materials This study included 20 patients who underwent trimodality therapy (CRT + surgery) and underwent 18 F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) both before and after CRT. Four groups of tumor features were examined: ( 1 ) conventional PET/CT response measures (eg, standardized uptake value [SUV] max , tumor diameter); ( 2 ) clinical parameters (eg, TNM stage, histology) and demographics; ( 3 ) spatial-temporal PET features, which characterize tumor SUV intensity distribution, spatial patterns, geometry, and associated changes resulting from CRT; and ( 4 ) all features combined. An optimal feature set was identified with recursive feature selection and cross-validations. Support vector machine (SVM) and logistic regression (LR) models were constructed for prediction of pathologic tumor response to CRT, cross-validations being used to avoid model overfitting. Prediction accuracy was assessed by area under the receiver operating characteristic curve (AUC), and precision was evaluated by confidence intervals (CIs) of AUC. Results When applied to the 4 groups of tumor features, the LR model achieved AUCs (95% CI) of 0.57 (0.10), 0.73 (0.07), 0.90 (0.06), and 0.90 (0.06). The SVM model achieved AUCs (95% CI) of 0.56 (0.07), 0.60 (0.06), 0.94 (0.02), and 1.00 (no misclassifications). With the use of spatial-temporal PET features combined with conventional PET/CT measures and clinical parameters, the SVM model achieved very high accuracy (AUC 1.00) and precision (no misclassifications)—results that were significantly better than when conventional PET/CT measures or clinical parameters and demographics alone were used. For groups with many tumor features (groups 3 and 4), the SVM model achieved significantly higher accuracy than did the LR model. Conclusions The SVM model that used all features including spatial-temporal PET features accurately and precisely predicted pathologic tumor response to CRT in esophageal cancer.

IMPORTANCE: Brain metastasis (BM) rates are high in locally advanced non–small cell lung cancer (LA-NSCLC), approaching rates seen in small cell lung cancer, where prophylactic cranial irradiation (PCI) is standard of care. Although PCI decreases the incidence of BM in LA-NSCLC, a survival advantage has not yet been shown. OBJECTIVE: To determine if PCI improves survival in LA-NSCLC. DESIGN, SETTING, AND PARTICIPANTS: Radiation Therapy Oncology Group (RTOG) 0214 was a randomized phase 3 clinical trial in stage III NSCLC stratified by stage (IIIA vs IIIB), histologic characteristics (nonsquamous vs squamous) and therapy (no surgery vs surgery). The study took place at 291 institutions in the United States, Canada, and internationally. Of 356 patients with stage III NSCLC entered onto this study, 16 were ineligible; therefore, 340 patients were randomized. INTERVENTION FOR CLINICAL TRIALS: Observation vs PCI. MAIN OUTCOMES AND MEASURES: The primary outcome was overall survival (OS). The secondary end points were disease-free survival (DFS) and incidence of BM. RESULTS: Of the 340 total participants, mean (SD) age was 61 years; 213 of the participants were men and 127 were women. The median follow-up time was 2.1 years for all patients, and 9.2 years for living patients. The OS for PCI was not significantly better than observation (hazard ratio [HR], 0.82; 95% CI, 0.63-1.06; P = .12; 5- and 10-year rates, 24.7% and 17.6% vs 26.0% and 13.3%, respectively), while the DFS (HR, 0.76; 95% CI, 0.59-0.97; P = .03; 5- and 10-year rates, 19.0% and 12.6% vs 16.1% and 7.5% for PCI vs observation) and BM (HR, 0.43; 95% CI, 0.24-0.77; P = .003; 5- and 10-year rates, 16.7% vs 28.3% for PCI vs observation) were significantly different. Patients in the PCI arm were 57% less likely to develop BM than those in the observation arm. Younger patients (

Purpose To extract and study comprehensive spatial-temporal 18 F-labeled fluorodeoxyglucose ([ 18 F]FDG) positron emission tomography (PET) features for the prediction of pathologic tumor response to neoadjuvant chemoradiation therapy (CRT) in esophageal cancer. Methods and Materials Twenty patients with esophageal cancer were treated with trimodal therapy (CRT plus surgery) and underwent [ 18 F]FDG-PET/CT scans both before (pre-CRT) and after (post-CRT) CRT. The 2 scans were rigidly registered. A tumor volume was semiautomatically delineated using a threshold standardized uptake value (SUV) of ≥2.5, followed by manual editing. Comprehensive features were extracted to characterize SUV intensity distribution, spatial patterns (texture), tumor geometry, and associated changes resulting from CRT. The usefulness of each feature in predicting pathologic tumor response to CRT was evaluated using the area under the receiver operating characteristic curve (AUC) value. Results The best traditional response measure was decline in maximum SUV (SUV max ; AUC, 0.76). Two new intensity features, decline in mean SUV (SUV mean ) and skewness, and 3 texture features (inertia, correlation, and cluster prominence) were found to be significant predictors with AUC values ≥0.76. According to these features, a tumor was more likely to be a responder when the SUV mean decline was larger, when there were relatively fewer voxels with higher SUV values pre-CRT, or when [ 18 F]FDG uptake post-CRT was relatively homogeneous. All of the most accurate predictive features were extracted from the entire tumor rather than from the most active part of the tumor. For SUV intensity features and tumor size features, changes were more predictive than pre- or post-CRT assessment alone. Conclusion Spatial-temporal [ 18 F]FDG-PET features were found to be useful predictors of pathologic tumor response to neoadjuvant CRT in esophageal cancer.

BACKGROUND: The Radiation Therapy Oncology Group (RTOG) trial 97-14 revealed no difference between radiation delivered for painful bone metastases at a dose of 8 gray (Gy) in 1 fraction (single-fraction radiotherapy [SFRT]) and 30 Gy in 10 fractions (multifraction radiotherapy [MFRT]) in pain relief or narcotic use 3 months after randomization. SFRT for painful vertebral bone metastases (PVBM) has not been well accepted, possibly because of concerns about efficacy and toxicity. In the current study, the authors evaluated the subset of patients that was treated specifically for patients with PVBM. METHODS: PVBM included the cervical, thoracic, and/or lumbar spine regions. Among patients with PVBM, differences in retreatment rates and in pain relief, narcotic use, and toxicity 3 months after randomization were evaluated. RESULTS: Of 909 eligible patients, 235 (26%) had PVBM. Patients with and without PVBM differed in terms of the percentage of men (55% vs 47%, respectively; P = .03) and the proportion of patients with multiple painful sites (57% vs 38%, respectively; P < .01). Among those with PVBM, more patients who received MFRT had multiple sites treated (65% vs 49% for MFRT vs SFRT, respectively; P = .02). There were no statistically significant treatment differences in terms of pain relief (62% vs 70% for MFRT vs SFRT, respectively; P = .59) or freedom from narcotic use (24% vs 27%, respectively; P = .76) at 3 months. Significant differences in acute grade 2 through 4 toxicity (20% vs 10% for MFRT vs SFRT, respectively; P = .01) and acute grade 2 through 4 gastrointestinal toxicity (14% vs 6%, respectively; P = .01) were observed at 3 months, with lower toxicities seen in the patients treated with SFRT. Late toxicity was rare. No myelopathy was recorded. SFRT produced higher 3-year retreatment rates (5% vs 15%; P = .01). CONCLUSIONS: Results for the subset of patients with PVBM in the RTOG 94-17 randomized controlled trial were comparable to those for the entire population. SFRT produced less acute toxicity and a higher rate of retreatment than MFRT. SFRT and MFRT resulted in comparable pain relief and narcotic use at 3 months. Cancer 2013. © 2012 American Cancer Society.

Purpose The management of patients diagnosed with thymoma remains unclear. This report attempts to identify the impact of adjuvant radiotherapy on overall survival (OS) and cause-specific survival (CSS) in patients diagnosed with thymoma. Methods and Materials Patients diagnosed with thymic malignancy between 1973 and 2003 were retrospectively identified from centers participating in the Surveillance, Epidemiology, and End Results (SEER) program. Those patients classified as having thymic carcinoma were excluded from this analysis. OS and CSS were estimated by the Kaplan-Meier method. Outcomes for patients treated with and without radiation therapy were compared using the log-rank test. Multivariate analysis was performed with the Cox proportional hazards model to analyze factors predictive of OS and CSS. Results A total of 1,464 patients were identified as having thymic malignancy, and of these, 1,254 patients were identified as having malignant thymoma. The median follow-up time was 41 months (range, 4–337 months). Among patients who did not receive radiotherapy (RT), the 10-year rate of OS was 41% compared to 42% for those who did receive RT ( p = 0.06). The median OS for the patients who did not receive RT was 80 months compared to 97 months for those who did receive RT. In patients with Masaoka stage II–III malignancy, OS was significantly improved with RT ( p = 0.002), and a trend in improved CSS was observed ( p = 0.1). Patients were also analyzed based on resection status. For those patients who had an incomplete excision, the 10-year OS was 63% with RT and 46% without RT ( p = 0.38). On multivariate analysis, factors predictive of OS included age, extent of surgery, stage, and number of lymph nodes examined. Conclusions This study reports treatment results of a large cohort of patients who were diagnosed with malignant thymoma. This study demonstrates that the use of RT following resection for thymoma significantly improves OS for those with regional disease and marginally improves CSS.

The tumor volume has been established as a significant predictor of outcomes among patients with head-and-neck cancer undergoing radiotherapy alone. The present study attempted to add to the existing data on tumor volume as a prognostic factor among patients undergoing chemoradiotherapy.A total of 78 patients who had undergone definitive chemoradiotherapy for Stage III-IV squamous cell cancer of the hypopharynx, oropharynx, and larynx were identified. The primary tumor volumes were calculated from the treatment planning computed tomography scans, and these were correlated to the survival and tumor control data obtained from the retrospective analysis.The interval to progression correlated with the primary tumor volume (p = .007). The critical cutoff point for the tumor volume was identified as 35 cm(3), and patients with a tumor volume35 cm(3) had a significantly better prognosis than those with a tumor volume35 cm(3) at 5 years (43% vs. 71%, p = .010). Longer survival was also correlated with smaller primary tumor volumes (p = .022). Similarly, patients with a primary tumor volume35 cm(3) had a better prognosis in terms of both progression-free survival (61% vs. 33%, p = .004) and overall survival (84% vs. 41%, p =.001). On multivariate analysis, the primary tumor volume was the best predictor of recurrence (hazard ratio 4.7, 95% confidence interval 1.9-11.6; p = .001) and survival (hazard ratio 10.0, 95% confidence interval 2.9-35.1; p =.001). In contrast, the T stage and N stage were not significant factors. Analysis of variance revealed that tumors with locoregional failure were on average 21.6 cm(3) larger than tumors without locoregional failure (p = .028) and 27.1-cm(3) larger than tumors that recurred as distant metastases (p = .020).The results of our study have shown that the primary tumor volume is a significant prognostic factor in patients with advanced cancer of the head and neck undergoing definitive chemoradiotherapy and correlated with the treatment outcomes better than the T or N stage.

Background. We performed a pilot study using Trojan vaccines in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). These vaccines are composed of HLA-I and HLA-II restricted melanoma antigen E (MAGE)-A3 or human papillomavirus (HPV)-16 derived peptides, joined by furin-cleavable linkers, and linked to a "penetrin'' peptide sequence derived from HIV- TAT. Thirty-one patients with SCCHN were screened for the trial and 5 were enrolled. Methods. Enrolled patients were treated with 300 lg of Trojan peptide supplemented with Montanide and granulocyte-macrophage colony- stimulating factor (GM-CSF) at 4-week intervals for up to 4 injections. Results. Following vaccination, peripheral blood mononuclear cells (PBMCs) from 4 of 5 patients recognized both the full Trojan constructs and constituent HLA-II peptides, whereas responses to HLA-I restricted peptides were less pronounced. Conclusion. This treatment regimen seems to have acceptable toxicity and elicits measurable systemic immune responses against HLA-II restricted epitopes in a subset of patients with advanced SCCHN. V C 2012 Wiley Periodicals, Inc. Head Neck 34: 1734-1746, 2012

This repeated measures, prospective study was designed to explore and describe symptom dimensions, depressive symptoms, and uncertainty in newly diagnosed oropharyngeal and laryngeal cancer patients during and 1 month following treatment.A non-probability sample of 21 oropharyngeal and laryngeal cancer patients receiving definitive radiation completed the Memorial Symptom Assessment Scale, Beck Depression Inventory, and Mishel's Uncertainty in Illness Scale at treatment initiation, and at 5, 9, and 12 weeks.A common pattern of 11 symptoms, which changed as treatment progressed, was problematic for patients. Physical symptoms increased by 50% at week 5 and 9. Depression was experienced by 24% of patients. Uncertainty was found to be high at all time points and unexpectedly remained unchanged over time (p = 0.73). Positive correlations (p0.05) were found among number of symptoms, symptom distress, and depressive symptoms. Uncertainty was correlated (p0.05) statistically only to symptom distress.This study is the first to identify uncertainty in illness among oropharyngeal and laryngeal cancer patients and found it to be higher than for other cancer populations. Findings provide insights into the uncertainty of living through treatment and provide information for patient care. The consistent pattern of high levels of uncertainty during and 1 month after treatment suggests that the uncertainty related to acute illness could extend into chronic uncertainty which may interfere with a cancer survivor's adaption to daily living after treatment. Further research is needed to investigate other variables that influence uncertainty during treatment as well as 1 to 6 months after treatment for head and neck cancer.

Background This study analyzed the impact of timing of percutaneous endoscopic gastrostomy (PEG) tube placement on clinical endpoints in patients undergoing concurrent chemoradiation therapy (CRT). Methods In all, 111 patients who underwent CRT for locally advanced squamous cell carcinoma of the head and neck (SCCHN) were retrospectively analyzed to determine the effect of timing of PEG placement on weight loss, hospitalizations, and rates of PEG complications/dependence. Results Early PEG tube placement was correlated to reductions in weight loss during CRT (p < .001, R = 0.495), hospitalization for nutritional deficits (p = .011, R = 0.262), and magnitude of persistent weight loss at 6 weeks post-CRT (p = .003, R = 0.347). Disease control was the only predictor of PEG dependence. No differences were seen in PEG complication or dependence rates with earlier placement. Conclusions The results of our series show that patients with locally advanced SCCHN undergoing definitive CRT may derive significant clinical benefit from the early placement of PEG tubes for nutritional supplementation. © 2010 Wiley Periodicals, Inc. Head Neck, 2010

has shown a significant change, with a decline in squamous cell incidence in all race and gender groups, while adenocarcinomas have shown a fivefold rise. 1 In contrast to the literature on treatment of esophageal cancer until the late 1980s, which reported results for patients with predominantly squamous cell carcinomas, the newest clinical studies report on patients with adenocarcinoma versus squamous cell cancers in a 4:1 to 5:1 ratio. Heterogeneity of staging practices, surgical technique, and analysis of results by histology leaves ambiguity as to the optimal combination of treatment modalities in this disease and whether similar practices will give similar results for both histologies. A case of squamous cell carcinoma of the distal esophagus is discussed below to highlight these issues in light of current data.

Kilovoltage x-ray projection images (kV images for brevity) are increasingly available in image guided radiotherapy (IGRT) for patient positioning. These images are two-dimensional (2D) projections of a three-dimensional (3D) object along the x-ray beam direction. Projecting a 3D object onto a plane may lead to ambiguities in the identification of anatomical structures and to poor contrast in kV images. Therefore, the use of kV images in IGRT is mainly limited to bony landmark alignments. This work proposes a novel subtraction technique that isolates a slice of interest (SOI) from a kV image with the assistance of a priori information from a previous CT scan. The method separates structural information within a preselected SOI by suppressing contributions to the unprocessed projection from out-of-SOI-plane structures. Up to a five-fold increase in the contrast-to-noise ratios (CNRs) was observed in selected regions of the isolated SOI, when compared to the original unprocessed kV image. The tomographic image via background subtraction (TIBS) technique aims to provide a quick snapshot of the slice of interest with greatly enhanced image contrast over conventional kV x-ray projections for fast and accurate image guidance of radiation therapy. With further refinements, TIBS could, in principle, provide real-time tumor localization usingmore » gantry-mounted x-ray imaging systems without the need for implanted markers.« less

BACKGROUND. Respiration-induced tumor motion compensation using a treatment couch requires moving the patient at non-trivial speeds. The purpose of this work was to investigate motion sickness and stability of the patient's external surface due to a moving couch with respiration-comparable velocities and accelerations. MATERIAL AND METHODS. A couch was designed to move with a peak-peak displacement of 5 cm and 1 cm in the S-I and A-P directions, respectively, and a period of 3.6 s. Fifty patients completed a 16-question motion sickness assessment questionnaire (MSAQ) prior to, during, and after the study. Seven optical reflectors affixed to the abdomen of each patient were monitored by infrared cameras. The relationship between reflector positions under stationary and moving conditions was evaluated to assess the stability of the patient's external surface. RESULTS AND DISCUSSION. Among the 4800 responses, 95% were 1 (no discomfort) of 9, and there were no scores of 6 or higher. Mild discomfort (scores of 4-5) was similar during couch motion and before couch motion (p = 0.39). Mild discomfort was less common after couch motion (p = 0.039) than before or during couch movement. There was a near 1:1 correspondence between marker-pair regression coefficients and phase offset values during couch-stationary and couch-moving conditions. Our results show that patients do not suffer motion sickness or external surface instability on a moving couch.

Purpose To determine whether the addition of recombinant human erythropoietin (Epo) could improve the outcomes of anemic patients receiving definitive radiotherapy for squamous cell carcinoma of the head and neck (SCCHN). Methods and Materials Eligible patients had SCCHN, with a plan for continuous-course definitive radiotherapy (66–72 Gy) with or without chemotherapy. Patients with Stage III or IV SCCHN were required to undergo concurrent chemoradiotherapy and/or accelerated fractionation radiotherapy. Preradiotherapy hemoglobin was required to be between 9.0 g/dL and 13.5 g/dL (12.5 g/dL for women). Patients randomized to Epo received 40,000 U once weekly, starting 7–10 days before start of radiotherapy. Results A total of 148 patients were enrolled; 141 were evaluable. Median pretreatment hemoglobin was 12.1 g/dL. Hemoglobin levels at 4 weeks rose by an average of 1.66 g/dL in the Epo arm, compared with an average 0.24 g/dL decrease in the control arm (p = 0.0001). Median follow-up was 2.5 years (3.1 years for surviving patients). There was no statistically significant difference in the primary endpoint of local–regional failure (LRF) rate between the treatment arms. The 3-year LRF rate was 36% for control and 44% for Epo (p = 0.56). There were also no significant differences in local–regional progression-free survival (LRPFS), patterns of failure, overall survival, or toxicity. The 3-year LRPFS rate was 52% for control and 47% for Epo. The overall survival rate was 57% and 56%, respectively. Conclusions The addition of Epo to definitive radiotherapy for SCCHN did not improve outcomes. The study was not specifically designed to detect a potential negative association between Epo and tumor progression/survival.

A significant number of patients diagnosed with esophageal cancer will present with locally advanced disease. The appropriate management of these patients continues to be a matter of significant debate. Over the past 2 decades, concurrent chemoradiation has been widely recognized as a viable option for a majority of these patients. Although there have been no randomized trials comparing definitive chemoradiation with surgical resection, there is little doubt that nonoperative therapy offers comparative opportunity for cure with less intendent morbidity and mortality. The broad applicability of this treatment option has led investigators to study methods of maximizing the therapeutic gain associated with the combination of external beam radiation and systemic chemotherapy. The long-term survival results have compared favorably with surgical series, thus leading to clinical trials designed to define the role of surgery in future management strategies. The early evaluation of these recent trials fails to identify any significant advantage associated with the routine use of surgery for most patients. Recent advances in drug development in conjunction with the identification of specific molecular targets has provided new opportunities to improve on the outcomes achieved with standard chemoradiation combinations.

Purpose: Local failure and toxicity to adjacent critical structures is a significant problem in radiation therapy of cancers of the head and neck. We are developing a gene therapy based method of sensitizing head/neck squamous cell carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary disorder, Nijmegen breakage syndrome, show radiation sensitivity we hypothesized that tumor-specific disruption of the function of the Nbs1 protein would lead to enhanced cellular sensitivity to ionizing radiation. Experimental Procedures: We constructed two recombinant adenoviruses by cloning the full-length Nbs1 cDNA as well as the C-terminal 300 amino acids of Nbs1 into an adenovirus backbone under the control of a CMV promoter. The resulting adenoviruses were used to infect HNSCC cell line JHU011. These cells were evaluated for expression of the viral based constructs and assayed for clonogenic survival following radiation exposure. Results: Exposure of cells expressing Nbs1-300 to ionizing radiation resulted in a small reduction in survival relative to cells infected with control virus. Surprisingly, expression of full-length Nbs1 protein resulted in markedly enhanced sensitivity to ionizing radiation. Furthermore, the use of a fractionated radiation scheme following virus infection demonstrates that expression of full-length Nbs1 protein results in significant reduction in cell survival. Conclusions: These results provide a proof of principle that disruption of Nbs1 function may provide a means of enhancing the radiosensitivity of head and neck tumors. Additionally, this work highlights the Mre11 complex as an attractive target for development of radiation sensitizers.

Objective To study whether subvolumes with a high pre-chemoradiotherapy (CRT) FDG uptake could identify residual metabolically-active volumes (MAVs) post-CRT within individual esophageal tumors. Accurate identification will allow simultaneous integrated boost to these subvolumes at higher risk to improve clinical outcomes. Methods Twenty patients with esophageal cancer were treated with CRT plus surgery and underwent FDG PET/CT scans before and after CRT. The two scans were rigidly registered. Seven MAVs pre-CRT and four MAVs post-CRT within a tumor were defined with various SUV thresholds. The similarity and proximity between the MAVs pre-CRT and post-CRT were quantified with three metrics: fraction of post-CRT MAV included in pre-CRT MAV, volume overlap and centroid distance. Results Eight patients had no residual MAV. Six patients had local residual MAV (SUV ≥2.5 post-CRT) within or adjoining the original MAV (SUV ≥2.5 pre-CRT). On average, less than 65% of any post-CRT MAVs was included in any pre-CRT MAVs, with a low volume overlap 8.6 mm. In general, subvolumes with higher FDG-uptake pre-CRT or post-CRT had lower volume overlap and larger centroid distance. Six patients had new distant MAVs that were determined to be inflammation from radiation therapy. Conclusions Pre-CRT PET/CT cannot reliably identify the residual MAVs within individual esophageal tumors. Simultaneous integrated boost to subvolumes with high FDG uptake pre-CRT may not be feasible.

Head and neck cancers are common malignancies that present considerable treatment challenges in terms of disease control and patient morbidity. Over several decades, the management of head and neck malignancies has moved from single modality to multimodality treatment, with an emphasis on disease control and organ preservation. The combination of chemotherapy and radiotherapy forms the cornerstone of current treatment paradigms for locally advanced head and neck cancers. Advances in altered fractionation and delivery techniques, effective chemotherapy combinations, novel biologic treatments, and risk stratification have led to improved disease control, decreased treatment-related morbidity, and improved patient quality of life. The role of stereotactic radiotherapy in head and neck cancers has made considerable advances in the past decade. These advances stem from progress in tumor identification and delineation, image guidance, patient immobilization, and treatment planning and delivery. Stereotactic radiosurgery and stereotactic body radiotherapy are becoming more widely used in the setting of reirradiation for head and neck malignancies. Ongoing research aims to improve the safety and efficacy of stereotactic radiotherapy for head and neck cancers.

Background: Docetaxel (Taxotere®) has gained increasing attention in clinical applications. We investigated the cytotoxic and radiosensitizing potential of docetaxel at nanomolar concentrations in six cell lines derived from tumors that rarely respond to radiation or chemotherapy, with special consideration of mechanisms of resistance, including the p53 mutational status. Methods: Cells derived from carcinomas of the human stomach (p53 mutant Hs746T, p53 wild type AGS), cervix (p53 wild type CaSki, p53 mutant HeLa) or pancreas (p53 mutant BxPC3 and Capan-1) were treated for 24 h with docetaxel at various concentrations (0.1–5 nM) to obtain drug doses for inhibiting clonogenicity by approximately 50% (IC50). Cells were X-irradiated without docetaxel or after 24 h of docetaxel treatment at IC50. Radiation doses ranged from 0 up to 10 Gy. Mitotic index, multinucleation, apoptosis and necrosis after 24 h of drug exposure at 1 nM were quantified in representative gastric and cervical cell lines by fluorescence microscopy. Results: Docetaxel treatment for 24 h resulted in a dose-dependent loss of clonogenicity, with 1.0 or 0.3 nM producing approximately 50% survival of gastric or cervix and pancreatic cells, respectively. After correction for the drug toxicity, the combination of isoeffective concentrations of docetaxel with graded X-ray doses resulted either in a moderate synergy or additivity. The dose reduction factors at the 50 and 20% survival levels were statistically greater than those for Hs746T or AGS cells. For CaSki, HeLa, BxPC3 or Capan-1 cells, the dose reduction factors were statistically not different from unity. Conclusion: Docetaxel was active against tumor cells of different origins. Combined effects of docetaxel and radiation were at least additive and depended on the intrinsic sensitivity to drug alone. There was no significant evidence of drug-induced mitotic arrest. Compared to drug-resistant gastric cells, exposure to the drug alone of drug-sensitive cervical cells resulted in more severe multinucleation. The p53 status did not contribute directly to the effect of drug alone or in combination with radiation.